@article{barron_defrancesco_chou_bonagura_tropf_murphy_mcmanamey_yuan_mochel_ward_2023, title={Echocardiographic caudal vena cava measurements in healthy cats and in cats with congestive heart failure and non-cardiac causes of cavitary effusions}, volume={48}, ISSN={["1875-0834"]}, url={https://doi.org/10.1016/j.jvc.2023.05.004}, DOI={10.1016/j.jvc.2023.05.004}, abstractNote={Echocardiographic indices of the inferior vena cava have been associated with elevated right atrial pressures in humans.Describe caudal vena caval (CVC) sonographic dimensions in healthy cats compared to cats with cardiogenic cavitary effusion (CCE), cardiogenic pulmonary edema (CPE), or non-cardiac causes of cavitary effusion (NCE).30 healthy control cats and 52 client-owned cats with CCE, CPE, or NCE examined at two university hospitals.Sagittal 2-dimensional (2D) and M-mode CVC dimensions were acquired from the subxiphoid view. Caudal vena cava collapsibility index (CVC-CI) was calculated. Variables were compared between study groups using Kruskal-Wallis and Dunn's Bonferroni testing. Receiver operating characteristic curves were used to assess sensitivity and specificity for diagnostic categories.Healthy cats had sagittal 2D and M-mode (median, interquartile range) CVC maximal dimensions of 2.4 mm (1.3-4.0) and 3.4 mm (1.5-4.9) and CVC-CI of 52% (45.2-61.8) and 55% (47.8-61.3), respectively. The CVC maximal dimensions in healthy controls were smaller than in cats with cavitary effusions or pulmonary edema (all P<0.05). CVC-CI was different between CCE and NCE (P<0.0001) with cutoffs of CVC-CI ≤38% (2D) or ≤29% (M-mode) being 90.5% and 85.7% sensitive, and 94.4% and 100% specific for diagnosis of CCE, respectively.Caudal vena cava measurements are larger in cats with cavitary effusions and cats with CPE than healthy cats. In cats with cavitary effusion, decreased CVC-CI, ≤38% (2D) or ≤29% (M-mode), was helpful in distinguishing between cardiogenic and noncardiogenic etiology.}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Barron, L. Z. and DeFrancesco, T. C. and Chou, Y. -y. and Bonagura, J. D. and Tropf, M. A. and Murphy, S. D. and McManamey, A. K. and Yuan, L. and Mochel, J. P. and Ward, J. L.}, year={2023}, month={Aug}, pages={7–18} }
 @article{walker_defrancesco_bonagura_keene_meurs_tou_kurtz_aona_barron_mcmanamey_et al._2022, title={Association of diet with clinical outcomes in dogs with dilated cardiomyopathy and congestive heart failure*}, volume={40}, ISSN={["1875-0834"]}, DOI={10.1016/j.jvc.2021.02.001}, abstractNote={Dilated cardiomyopathy (DCM) in dogs has been associated with feeding of grain-free (GF), legume-rich diets. Some dogs with presumed diet-associated DCM have shown improved myocardial function and clinical outcomes following a change in diet and standard medical therapy. Prior GF (pGF) diet influences reverse cardiac remodeling and clinical outcomes in dogs with DCM and congestive heart failure (CHF). A retrospective study was performed with 67 dogs with DCM and CHF for which diet history was known. Dogs were grouped by diet into pGF and grain-inclusive (GI) groups. Dogs in the pGF group were included if diet change was a component of therapy. Survival was analyzed using Kaplan–Meier curves and the Cox proportional-hazards model. The median survival time was 344 days for pGF dogs vs. 253 days for GI dogs (P = 0.074). Statistically significant differences in median survival were identified when the analysis was limited to dogs surviving longer than one week (P = 0.033). Prior GF dogs had a significantly worse outcome the longer a GF diet was fed prior to diagnosis (P = 0.004) or if they were diagnosed at a younger age (P = 0.017). Prior GF dogs showed significantly greater improvement in normalized left ventricular internal diastolic diameter (P = 0.038) and E-point septal separation (P = 0.031) measurements and significant decreases in their furosemide (P = 0.009) and pimobendan (P < 0.005) dosages over time compared to GI dogs. Prior GF dogs that survived at least one week after diagnosis of DCM, treatment of CHF, and diet change had better clinical outcomes and showed reverse ventricular remodeling compared to GI dogs.}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Walker, A. L. and DeFrancesco, T. C. and Bonagura, J. D. and Keene, B. W. and Meurs, K. M. and Tou, S. P. and Kurtz, K. and Aona, B. and Barron, L. and McManamey, A. and et al.}, year={2022}, month={Apr}, pages={99–109} }
 @article{guillaumin_defrancesco_scansen_quinn_whelan_hanel_goy-thollot_bublot_robertson_bonagura_2022, title={Bilateral lysis of aortic saddle thrombus with early tissue plasminogen activator (BLASTT): a prospective, randomized, placebo-controlled study in feline acute aortic thromboembolism}, volume={11}, ISSN={["1532-2750"]}, DOI={10.1177/1098612X221135105}, abstractNote={Objectives The aim of this study was to investigate the impact of tissue plasminogen activator (TPA) on the treatment of feline aortic thromboembolism (FATE). Methods Cats diagnosed with FATE involving ⩾2 limbs were enrolled in a prospective, multicenter, double-blinded, randomized, placebo-controlled study within 6 h of an event. Diagnosis was made by clinical findings and one confirmatory criterion. Cats received placebo or TPA (1 mg/kg/h with the first 10% by bolus). All cats received pain control and thromboprophylaxis. The primary outcome was a change from baseline in a published limb score at 48 h. Secondary outcomes included 48 h survival, survival to discharge and complication proportions. Statistical analyses included pattern-mixture models, logistic regression and Fisher’s exact, Student’s t- and Mann–Whitney–Wilcoxon tests. Results Based on a power analysis, 40 cats were enrolled; however, only 20 survived to 48 h (TPA, n = 12; placebo, n = 8 [ P = 0.34]). There was a statistically significant improvement in limb scores compared with baseline for both groups ( P <0.001). Limb score at 48 h was 1 point lower (better) in the TPA group ( P = 0.19). Thrombolysis had no statistically significant effect on 48 h survival ( P = 0.22). Lower affected limb lactate was associated with better 48 h survival (odds ratio 1.53, 95% confidence interval 1.08–2.17; P = 0.02). The survival to discharge rates were 45% (TPA) and 30% (placebo; P = 0.51). Complications in the TPA and placebo groups included acute kidney injury (22% and 19%, respectively; P = 1.00) and/or reperfusion injuries (33% and 19%, respectively; P = 0.45). Conclusions and relevance Survival and complication rates of acute FATE were not different with or without thrombolysis. High in-hospital mortality decreased the statistical power to detect a statistically significant difference between treatments with regard to our primary outcome.}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Guillaumin, Julien and DeFrancesco, Teresa C. and Scansen, Brian A. and Quinn, Rebecca and Whelan, Megan and Hanel, Rita and Goy-Thollot, Isabelle and Bublot, Isabelle and Robertson, James B. and Bonagura, John D.}, year={2022}, month={Nov} }
 @article{bonagura_visser_2022, title={Echocardiographic assessment of dilated cardiomyopathy in dogs}, volume={40}, ISSN={["1875-0834"]}, url={https://doi.org/10.1016/j.jvc.2021.08.004}, DOI={10.1016/j.jvc.2021.08.004}, abstractNote={Dilated cardiomyopathy (DCM) is a frequent cause of cardiac disability, congestive heart failure (CHF), and arrhythmic death in dogs. The etiology of DCM is usually idiopathic/genetic, but some causes of a DCM phenotype are reversible. The disease is classified into preclinical (occult) and clinical (overt) stages; the latter stems from heart failure with reduced ejection fraction. DCM is further characterized by clinical, electrocardiographic, circulating biomarker, and imaging abnormalities. The diagnosis of clinical DCM with CHF is straightforward; however, identification of the preclinical stage can be challenging. Echocardiography is central to the diagnosis of both stages and characterized by left ventricular (LV) systolic dysfunction with progressive chamber dilation and variable enlargements of the left atrium and right-sided chambers. Left ventricular dilation is defined by increased LV end-diastolic volumes, areas, and internal dimensions normalized to body size or indexed to the aorta. Systolic dysfunction is characterized by decreased LV ejection fraction, increased end-systolic volume, and reduced shortening across minor and longitudinal LV axes. Dyssynchrony can confound the interpretation of linear indices of systolic function. A comprehensive echocardiogram in DCM includes two-dimensional and M-mode studies, spectral and tissue Doppler imaging, and potentially three-dimensional echocardiography and myocardial strain imaging. Echocardiographic findings should be interpreted within the context of identifiable risks and comorbidities, physical diagnosis, complementary diagnostic testing, and limitations of current reference intervals. Ambiguous examinations should be repeated. Specific echocardiographic criteria for the diagnosis of DCM are proposed to encourage discussion and additional outcome and breed-specific echocardiographic studies of canine DCM.}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, publisher={Elsevier BV}, author={Bonagura, J. D. and Visser, L. C.}, year={2022}, month={Apr}, pages={15–50} }
 @article{winter_rhinehart_estrada_maisenbacher_claretti_bussadori_nguyenba_scansen_bonagura_schober_2021, title={Repeat balloon valvuloplasty for dogs with recurrent or persistent pulmonary stenosis}, volume={34}, ISSN={["1875-0834"]}, url={https://doi.org/10.1016/j.jvc.2020.12.006}, DOI={10.1016/j.jvc.2020.12.006}, abstractNote={Pulmonary stenosis (PS) is a common congenital defect in the dog. Severe valvar PS can be treated with balloon valvuloplasty (BV) to reduce obstruction severity and improve clinical signs. Repeat BV is often unnecessary, as restenosis is uncommon. Repeated pulmonary BV in people is generally successful and safe, but outcomes in dogs with recurrent or persistent stenosis have not been reported. The objectives of this study were to retrospectively evaluate outcomes of repeat BV in dogs.Medical records and stored echocardiographic images were reviewed from dogs that received repeat BV for pulmonary valvar restenosis or persistent stenosis. Echocardiographic variables included maximum systolic ejection velocity (PVmax), velocity-derived maximal pressure gradient (PGmax) and velocity time integral (VTI) across the pulmonary valve, and ratios of pulmonic to aortic maximum velocity (PVmax/AVmax) and VTI (VTIPV/VTIAV).Twenty-three dogs were included; one underwent three BV procedures. The median time between BV procedures was 18.3 months (interquartile range, 6.3-43.6). One dog died during repeat BV, but no others experienced adverse effects. Reductions in PVmax, PGmax, and VTIPV after initial and repeat BV were 1.85 m/s, 76.2 mmHg, and 44.7 cm and 1.33 m/s, 55.6 mmHg, and 30.2 cm, respectively (all p < 0.01). Differences between pre-BV and post-BV PVmax, PGmax, VTIPV, PVmax/AVmax, and VTIPV/VTIAV were not different comparing initial to repeat BV (all p > 0.10).Repeat BV for recurrent or persistent PS is well tolerated and effective in a majority of dogs.}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, publisher={Elsevier BV}, author={Winter, R. L. and Rhinehart, J. D. and Estrada, A. H. and Maisenbacher, H. W., III and Claretti, M. and Bussadori, C. M. and Nguyenba, T. P. and Scansen, B. A. and Bonagura, J. D. and Schober, K. E.}, year={2021}, month={Apr}, pages={29–36} }
 @article{boswood_gordon_haggstrom_vanselow_wess_stepien_oyama_keene_bonagura_macdonald_et al._2020, title={Temporal changes in clinical and radiographic variables in dogs with preclinical myxomatous mitral valve disease: The EPIC study}, volume={34}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.15753}, abstractNote={The Evaluation of pimobendan in dogs with cardiomegaly caused by preclinical myxomatous mitral valve disease (EPIC) study monitored dogs with myxomatous mitral valve disease (MMVD) as they developed congestive heart failure (CHF).To describe the changes in clinical and radiographic variables occurring as dogs with MMVD and cardiomegaly develop CHF, compared to similar dogs that do not develop CHF.One hundred and thirty-five, and 73 dogs that did or did not develop CHF, respectively.The following variables were evaluated in 2 groups of dogs (dogs that did or did not develop CHF): Heart rate (HR), clinic respiratory rate (RR), home-measured resting respiratory rate (RRR), rectal temperature (RT), body weight (BW), and vertebral heart sum (VHS). Absolute value and rate of change of each variable were calculated for each day a dog was in study. Daily means were calculated and plotted against time. The onset of CHF or last visit before leaving the study were set as reference time points.The most extreme values and rate of change occurred in variables immediately before onset of CHF. Vertebral heart sum increased earliest. Heart rate, RR, and RRR also increased. Rectal temperature and BW decreased. Increases in RR and RRR were most extreme and occurred immediately before CHF.Dogs with MMVD and cardiomegaly experience increases in HR, RR, RRR, and VHS, and decreases in BW and RT as they develop CHF. The variables with highest absolute change and rate of change were RR and RRR. These findings reinforce the value of RR and RRR as indicators of impending or incipient CHF.}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Boswood, Adrian and Gordon, Sonya G. and Haggstrom, Jens and Vanselow, Martin and Wess, Gerhard and Stepien, Rebecca L. and Oyama, Mark A. and Keene, Bruce W. and Bonagura, John and MacDonald, Kristin A. and et al.}, year={2020}, month={May}, pages={1108–1118} }
 @article{keene_atkins_bonagura_fox_haggstrom_fuentes_oyama_rush_stepien_uechi_et al._2019, title={ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs}, volume={33}, ISSN={["1939-1676"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85064530654&partnerID=MN8TOARS}, DOI={10.1111/jvim.15488}, abstractNote={This report, issued by the ACVIM Specialty of Cardiology consensus panel, revises guidelines for the diagnosis and treatment of myxomatous mitral valve disease (MMVD, also known as endocardiosis and degenerative or chronic valvular heart disease) in dogs, originally published in 2009. Updates were made to diagnostic, as well as medical, surgical, and dietary treatment recommendations. The strength of these recommendations was based on both the quantity and quality of available evidence supporting diagnostic and therapeutic decisions. Management of MMVD before the onset of clinical signs of heart failure has changed substantially compared with the 2009 guidelines, and new strategies to diagnose and treat advanced heart failure and pulmonary hypertension are reviewed.}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Keene, Bruce W. and Atkins, Clarke E. and Bonagura, John D. and Fox, Philip R. and Haggstrom, Jens and Fuentes, Virginia Luis and Oyama, Mark A. and Rush, John E. and Stepien, Rebecca and Uechi, Masami and et al.}, year={2019}, month={May}, pages={1127–1140} }
 @article{bonagura_2019, title={Overview of Equine Cardiac Disease}, volume={35}, ISSN={["1558-4224"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85062658765&partnerID=MN8TOARS}, DOI={10.1016/j.cveq.2019.01.001}, abstractNote={Equine heart diseases can be categorized with morphologic, etiologic, and physiologic diagnoses and classified anatomically as diseases of the pericardium, myocardium, valves (endocardium), and great vessels. An appreciation of normal and pathologic physiology is a key to understanding diagnosis and therapy of heart disease. Pathophysiologic diagnoses include arrhythmias, congestive heart failure, and pulmonary hypertension. Heart rhythm disturbances can occur in isolation or with structural disease. Heart failure stems from arterial filling owing to insufficient cardiac output. Pulmonary hypertension is associated with strenuous exercise, left heart failure, bronchopulmonary diseases, and pulmonary arteriopathies. The etiopathogenesis of these disorders are incompletely understood.}, number={1}, journal={VETERINARY CLINICS OF NORTH AMERICA-EQUINE PRACTICE}, author={Bonagura, John D.}, year={2019}, month={Apr}, pages={1-+} }
 @article{guillaumin_gibson_goy-thollot_bonagura_2019, title={Thrombolysis with tissue plasminogen activator (TPA) in feline acute aortic thromboembolism: a retrospective study of 16 cases}, volume={21}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85047818501&partnerID=MN8TOARS}, DOI={10.1177/1098612X18778157}, abstractNote={Objectives Thrombolytic therapy is a treatment of choice for people with acute ischemic events, but is uncommonly administered for feline aortic thromboembolism (FATE). This study reports selected clinical data and outcomes of acute FATE treated with tissue plasminogen activator (TPA). A reference group treated with current standard of care (SOC) was analyzed for comparison. Methods This was a retrospective study of FATE in two academic hospitals. TPA-treated cats with two or more limbs (n = 16) affected were compared with a SOC-treated group with two or more limbs affected (n = 38). A limb score based on motor function and pulse quality was calculated for each group. Results Limb score and proportion of congestive heart failure at admission was similar in both groups. Time from FATE to admission was shorter in the TPA group, with a median of 3 h (range 0–6 h) vs 6 h (range 0–48 h; P = 0.0004). The most common regimen received for TPA was 1 mg/kg over 1 h. Other treatments were similar to those of the SOC group and included analgesia, thromboprophylaxis and furosemide. Documented complications for TPA-treated cats included reperfusion injury (5/10) and acute kidney injury (AKI; 3/10). Discharge proportion rate was 44% (TPA) vs 29% (SOC; P = 0.351). There were no differences in short-term survival rate (56.2% vs 39.5%; P = 0.369), clinical improvement (56.2% vs 31%; P = 0.122), rates of reperfusion injury (50% vs 50%; P = 1.00) or AKI (30% vs 27%; P = 1.00) between the TPA-treated and SOC groups, respectively. Conclusions and relevance Survival and complication rates of TPA-treated cats and SOC-treated cats for acute FATE were similar.}, number={4}, journal={Journal of Feline Medicine and Surgery}, author={Guillaumin, J. and Gibson, R.M.B. and Goy-Thollot, I. and Bonagura, J.D.}, year={2019}, pages={340–346} }
 @article{rohrbaugh_schober_bonagura_cheatham_rhinehart_berman_2019, title={Treatment of caudal cavoatrial junction obstruction in a dog with a balloon-expandable biliary stent}, volume={23}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85063378425&partnerID=MN8TOARS}, DOI={10.1016/j.jvc.2019.02.004}, abstractNote={A 2-year-old intact female mixed breed dog was presented for ascites. Echocardiography demonstrated severe obstruction at the level of the caudal right atrium. Initially, a variant of cor triatriatum dexter was diagnosed, and balloon catheter dilation was performed. However, ascites recurred within a week. Further imaging revealed an obstruction at the entrance of the caudal vena cava into the right atrium rather than a dividing membrane in the right atrium. The diagnosis was revised to suprahepatic obstruction of the caudal vena cava because of remnant Eustachian valve tissue. Deployment of a balloon-expandable biliary stent was performed relieving the obstruction. Fifteen months after stent deployment, the patient is doing well without reaccumulation of ascitic fluid.}, journal={Journal of Veterinary Cardiology}, author={Rohrbaugh, M. and Schober, K.E. and Bonagura, J.D. and Cheatham, S. and Rhinehart, J. and Berman, D.}, year={2019}, pages={112–121} }
 @article{bonagura_2018, title={Avant-propos}, DOI={10.1016/b978-2-294-74873-8.09982-3}, journal={Encyclopédie Animée D'imagerie Cardiovasculaire Ultrasonore du Chien et du Chat}, publisher={Elsevier}, author={Bonagura, John D.}, year={2018}, pages={v-vi} }
 @article{divincenzo_bonagura_rings_burns_cianciolo_kohnken_2018, title={Cardiovascular images: vascular hamartoma of the mitral valve in a horse}, volume={20}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85054909146&partnerID=MN8TOARS}, DOI={10.1016/j.jvc.2018.09.002}, abstractNote={An 8-month-old Hanoverian gelding was presented with a history of cardiac murmurs that were not apparent as a foal nor reported at the time of castration. Major echocardiographic findings included mitral valvular thickening, functional stenosis, and mitral regurgitation of sufficient severity to cause diastolic and systolic cardiac murmurs, left-sided volume overload, and pulmonary hypertension. Due to the hemodynamic severity of the lesion and poor prognosis for future performance and longevity, euthanasia was elected. On gross postmortem examination, there was focal fibrous epicarditis affecting the heart base, and the left atrium was moderately dilated. The mitral valve surface was irregular and contained several nodules along the atrial face of the cusp. Histologically, this lesion was diagnosed as a vascular hamartoma, which is rarely reported in veterinary species and has not been described in heart valves. This benign proliferative lesion, and concurrent valvular dysfunction, was associated with an unusual manifestation of clinically evident disease and should be differentiated from common incidental valvular lesions such as hematocysts.}, number={6}, journal={Journal of Veterinary Cardiology}, author={DiVincenzo, M.J. and Bonagura, J.D. and Rings, L. and Burns, T.A. and Cianciolo, R.E. and Kohnken, R.}, year={2018}, pages={399–404} }
 @article{chapel_scansen_schober_bonagura_2018, title={Echocardiographic Estimates of Right Ventricular Systolic Function in Dogs with Myxomatous Mitral Valve Disease}, volume={32}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85041007569&partnerID=MN8TOARS}, DOI={10.1111/jvim.14884}, abstractNote={Right ventricular (RV) dysfunction independently predicts outcomes in human myxomatous mitral valve disease (MMVD). There is limited information regarding RV systolic function in dogs with MMVD.Right ventricular systolic function differs among stages of disease, decreasing in decompensated MMVD.Thirty-sixclient-owned dogs with MMVD not receiving oral cardiovascular medications.Prospective clinical study. Dogs were categorized according to disease severity as ACVIM Stage B1, B2, or C. Seven echocardiographic indices of RV systolic function were measured. Groups were compared by 1-way ANOVA and Tukey's HSD test. Frequencies of cases with cardiac remodeling falling outside previously established reference intervals were compared using Fisher's exact test. Intra- and interobserver measurement variability was calculated for each RV function index.The indices TAPSE (P = 0.029), RV StL (P = 0.012), and RV StRL (P = 0.041) were significantly different between groups. A greater proportion of B2 dogs (7 of 12) had TAPSE values above reference intervals compared with B1 (2 of 12) or C (2 of 12) dogs (P = 0.027). Measurement variability of TAPSE, RV S', and RV StG was clinically acceptable.Right ventricular systolic function differs between stages of MMVD, increasing in stage B2, and declining in stage C. The prognostic importance of RV function indices, particularly TAPSE, might be worth evaluating in dogs with MMVD.}, number={1}, journal={Journal of Veterinary Internal Medicine}, author={Chapel, E.H. and Scansen, B.A. and Schober, K.E. and Bonagura, J.D.}, year={2018}, pages={64–71} }
 @article{scaglione_diaz_bonagura_kohnken_helms_cianciolo_2018, title={Ischemic necrosis of the digits and hyperlipidemia associated with atherosclerosis in a Miniature American Shepherd}, volume={253}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85049456949&partnerID=MN8TOARS}, DOI={10.2460/javma.253.2.209}, abstractNote={CASE DESCRIPTION A 2.5-year-old 12-kg (26.4-lb) castrated male Miniature American Shepherd was referred because of a 3-week history of a localized crusted skin lesion on the digital pad of digit 3 of the right hind limb. CLINICAL FINDINGS Skin lesions were noted on the digital pads of the right hind limb. Serum biochemical analyses indicated severe hypercholesterolemia and hypertriglyceridemia. Ultrasonography of the terminal portion of the aorta and other major arterial vessels revealed substantial arteriosclerotic change. TREATMENT AND OUTCOME Medical treatments included administration of atorvastatin calcium, a low-fat diet, and omega-3 fatty acids to reduce serum lipids concentration; clopidogrel to prevent thrombosis; pentoxifylline to improve microcirculatory blood flow; clomipramine hydrochloride and trazodone hydrochloride to help with the behavioral problems; and gabapentin to help with pain management and behavioral problems. Surgical management included amputation of the initial digit involved, then eventually the entire initial limb involved. The response to treatment was poor, and euthanasia was elected. Postmortem findings revealed severe, widespread, and chronic intimal atherosclerosis; mild, widespread, and degenerative changes in the cerebral cortex; and edema and vascular congestion in the meninges. CLINICAL RELEVANCE To the authors' knowledge, this was the first report of skin necrosis secondary to atherosclerosis in a dog. Although the incidence of atherosclerosis has been considered very low in dogs, it should be investigated in dogs with severe hyperlipidemia. Primary hyperlipidemia has not been previously described in Miniature American Shepherd dogs but was the suspected underlying metabolic disorder.}, number={2}, journal={Journal of the American Veterinary Medical Association}, author={Scaglione, J. and Diaz, S.F. and Bonagura, J.D. and Kohnken, R.A. and Helms, T.H. and Cianciolo, R.E.}, year={2018}, pages={209–214} }
 @article{longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with preclinical myxomatous mitral valve disease receiving pimobendan or placebo: the epic study_2018, volume={32}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85040974900&partnerID=MN8TOARS}, DOI={10.1111/jvim.14885}, abstractNote={Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described.To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF.Three hundred and fifty-four dogs with MMVD and cardiomegaly.Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored.At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P < 0.0001, and LA:Ao -0.08 (IQR: -0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar.Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.}, number={1}, journal={Journal of Veterinary Internal Medicine}, year={2018}, pages={72–85} }
 @article{strohm_visser_chapel_drost_bonagura_2018, title={Two-dimensional, long-axis echocardiographic ratios for assessment of left atrial and ventricular size in dogs}, volume={20}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85051750048&partnerID=MN8TOARS}, DOI={10.1016/j.jvc.2018.07.008}, abstractNote={Left ventricular (LV) and left atrial (LA) enlargement affect management and outcome of dogs with cardiac disease. Short-axis, two-dimensional echocardiographic (2DE) images, indexed to the aorta (Ao), are frequently used to identify cardiomegaly. Long-axis images offer complementary views of the left heart.Eighty healthy dogs and 25 dogs with MMVD.Healthy dogs were prospectively recruited to determine reference intervals (Clinical Laboratory Standards Institute methodology) for long-axis ratios. Measurement variability and repeatability were quantified by intraclass correlation coefficient and coefficient of variation. Mean long-axis ratios from dogs with MMVD were compared with healthy dogs (unpaired t-test). In addition, the proportion of MMVD dogs exceeding the 97.5 percentile by LV/Ao and a conventional, allometric method were compared (McNemar's test).Two-dimensional echocardiographic long-axis reference intervals were as follows: left ventricular to aortic dimension (LV/Ao) 1.8-2.5; left atrial to aortic dimension (LA/Ao) 1.8-2.4, and left atrial to left ventricular dimension (LA/LV) 0.9-1.1. Intraobserver and interobserver measurement agreement was good-to-excellent (intraclass correlation coefficients ≥0.84), and day-to-day variability was low (coefficient of variations <4%). Left ventricular to aortic dimension, LA/Ao, and LA/LV were significantly greater in canine MMVD compared with healthy dogs (p<0.001). The percentages of MMVD dogs demonstrating LV dilatation by LV/Ao and conventional method were 68% and 36%, respectively (p=0.043, 95% confidence interval for difference 7.9%, 56.1%).Simple 2DE long-axis ratios of LV/Ao, LA/Ao, and LA/LV are repeatable and demonstrate clinical utility for identifying LV and LA enlargement in dogs with MMVD.}, number={5}, journal={Journal of Veterinary Cardiology}, author={Strohm, L.E. and Visser, L.C. and Chapel, E.H. and Drost, W.T. and Bonagura, J.D.}, year={2018}, pages={330–342} }
 @article{schober_rhinehart_kohnken_bonagura_2017, title={Cutting balloon and high-pressure balloon dilation for palliative treatment of congenital double-chambered right ventricle and primary infundibular stenosis in a Golden retriever dog}, volume={19}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85034439628&partnerID=MN8TOARS}, DOI={10.1016/j.jvc.2017.10.001}, abstractNote={Combined cutting balloon and high-pressure balloon dilation was performed in a dog with a double-chambered right ventricle and severe infundibular stenosis of the right ventricular outflow tract. The peak systolic pressure gradient across the stenosis decreased by 65% after dilation (from 187 mmHg before to 66 mmHg after) affirming the intervention as successful. However, early re-stenosis occurred within 3 months leading to exercise intolerance, exercise-induced syncope, and right-sided congestive heart failure. Cutting balloon followed by high-pressure balloon dilation provided temporary but not long-term relief of right ventricular obstruction in this dog.}, number={6}, journal={Journal of Veterinary Cardiology}, author={Schober, K.E. and Rhinehart, J. and Kohnken, R. and Bonagura, J.D.}, year={2017}, pages={538–546} }
 @article{rhinehart_schober_scansen_yildiz_bonagura_2017, title={Effect of Body Position, Exercise, and Sedation on Estimation of Pulmonary Artery Pressure in Dogs with Degenerative Atrioventricular Valve Disease}, volume={31}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85028603934&partnerID=MN8TOARS}, DOI={10.1111/jvim.14814}, abstractNote={Severity of pulmonary hypertension (PH) in dogs is related to clinical signs and prognosis.We hypothesized that Doppler echocardiographic (DE) indices of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) are influenced by independent factors that create clinically important variability of DE-based estimates of PH in dogs.Thirty-eight client owned dogs with naturally acquired degenerative atrioventricular valve disease and tricuspid regurgitation (TR).Dogs were prospectively enrolled, and target variables were acquired during 4 echocardiographic study periods (lateral recumbency, standing, lateral recumbency after a 6-minute walk test [6MWT], and lateral recumbency after sedation with butorphanol 0.25 mg/kg IM). Statistical methods included repeated measures ANOVA, mixed model analysis, and Chi-squared test of association.There was a significant increase in peak TR flow velocity (TRFV; P < 0.01) after sedation in 78% of dogs, with TRFV increasing by >0.4 m/s in 42% of dogs, independent of stroke volume. A significant effect of study period on DE-estimated PVR was not found (P = 0.15). There were negligible effects of sonographer, body position, and 6MWT on echocardiographic variables of PH. Clinically relevant cyclic variation of TRFV was found. There was an association between estimation of right atrial pressure based on subjective assessment and estimation based on cranial vena cava collapsibility (P = 0.03).The increase in TRFV observed with sedation could change assessment of PH severity and impact prognostication and interpretation of treatment response. Further studies with invasive validation are needed.}, number={6}, journal={Journal of Veterinary Internal Medicine}, author={Rhinehart, J.D. and Schober, K.E. and Scansen, B.A. and Yildiz, V. and Bonagura, J.D.}, year={2017}, pages={1611–1621} }
 @article{effect of pimobendan in dogs with preclinical myxomatous mitral valve disease and cardiomegaly: the epic study - a randomized clinical trial,die wirkung von pimobendan bei hunden mit praklinischer myxomatoser mitralklappen- erkrankung und kardiomegalie: die epic-studie - eine randomisierte klinische studie_2017, volume={62}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85016303285&partnerID=MN8TOARS}, DOI={10.2377/0023-2076-62-64}, number={2}, journal={Kleintierpraxis}, year={2017}, pages={64–87} }
 @article{schnedeker_cole_lorch_diaz_bonagura_daniels_2017, title={In vitro bactericidal activity of blue light (465 nm) phototherapy on meticillin-susceptible and meticillin-resistant Staphylococcus pseudintermedius}, volume={28}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85019556559&partnerID=MN8TOARS}, DOI={10.1111/vde.12451}, abstractNote={Background Staphylococcus pseudintermedius is the most common cause of bacterial skin infections in dogs. Meticillin‐resistant infections have become more common and are challenging to treat. Blue light phototherapy may be an option for treating these infections. Hypothesis/Objectives The objective of this study was to measure the in vitro bactericidal activity of 465 nm blue light on meticillin‐susceptible Staphylococcus pseudintermedius ( MSSP ) and meticillin‐resistant Staphylococcus pseudintermedius ( MRSP ). We hypothesized that irradiation with blue light would kill MSSP and MRSP in a dose‐dependent fashion in vitro as previously reported for meticillin‐resistant Staphylococcus aureus ( MRSA ). Methods In six replicate experiments, each strain [ MSSP , n = 1; MRSP ST ‐71 ( KM 1381) n = 1; and MRSA ( BAA ‐1680) n = 1] were cultivated on semisolid media, irradiated using a 465 nm blue light phototherapeutic device at the cumulative doses of 56.25, 112.5 and 225 J/cm 2 and incubated overnight at 35°C. Controls were not irradiated. Colony counts ( CC ) were performed manually. Descriptive statistics were performed and treatment effects assessed using the Wilcoxon–Mann – Whitney rank‐sum test. Bonferroni‐corrected rank‐sum tests were performed for post hoc analysis when significant differences were identified. Results There was a significant decrease in CC with blue light irradiation at all doses for MRSA ( P = 0.0006) but not for MSSP ( P = 0.131) or MRSP ( P = 0.589). Conclusions Blue light phototherapy significantly reduced CC of MRSA , but not of MSSP or MRSP . The mechanism for the relative photosensitivity of the MRSA isolate is unknown, but is hypothesized to be due to an increased concentration of porphyrin in S. aureus relative to S. pseudintermedius , which would modulate blue light absorption.}, number={5}, journal={Veterinary Dermatology}, author={Schnedeker, A.H. and Cole, L.K. and Lorch, G. and Diaz, S.F. and Bonagura, J. and Daniels, J.B.}, year={2017}, pages={106–463} }
 @article{effect of pimobendan in dogs with preclinical myxomatous mitral valve disease and cardiomegaly: the epic study—a randomized clinical trial_2016, volume={30}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84992446840&partnerID=MN8TOARS}, DOI={10.1111/jvim.14586}, abstractNote={Background Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. Hypothesis/Objectives Administration of pimobendan (0.4–0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac‐related death, or euthanasia. Animals 360 client‐owned dogs with MMVD with left atrial‐to‐aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5. Methods Prospective, randomized, placebo‐controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac‐related death, or euthanasia. Results Median time to primary endpoint was 1228 days (95% CI: 856–NA) in the pimobendan group and 766 days (95% CI: 667–875) in the placebo group ( P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47–0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952–NA) in the pimobendan group and 902 days (95% CI: 747–1061) in the placebo group) ( P = .012). Conclusions and Clinical Importance Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.}, number={6}, journal={Journal of Veterinary Internal Medicine}, year={2016}, pages={1765–1779} }
 @article{bonagura_2016, title={Feline Echocardiography}, volume={2}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034280351&partnerID=MN8TOARS}, DOI={10.1053/jfms.2000.0089}, abstractNote={Echocardiography is increasingly used for the diagnosis and management of congenital and acquired cardiac diseases. While a number of different echocardiographic formats are used in clinical practice, each involves reflection of ultrasound from cardiovascular tissues, specialised processing of returned (echoed) signals, and the ultimate display of this information in some recognisable visual or auditory format. Echocardiography has become increasingly sophisticated, and the combined modalities have largely replaced cardiac catheterisation and angiocardiography for diagnosis and assessment of cardiac lesions. Although the newest technologies are expensive and limited to referral hospitals and clinics, many practising veterinarians use, or will soon acquire, echocardiographs. Furthermore, veterinarians who are not yet performing echocardiographic studies, often find referral for echocardiography helpful or even essential for establishing a cardiac diagnosis, assessing ventricular function, determining a prognosis, and guiding medical or surgical therapy. The echocardiographic examination must be placed within a proper clinical perspective (Table 1). Most importantly, echocardiography is not a substitute for a careful clinical examination and routine diagnostic studies such as measurement of arterial blood pressure, determination of serum thyroxine, measurement of the PCV, and thoracic radiography. Cardiac auscultation is still a useful and expedient method for identifying serious heart diseases; however, it should be appreciated that a significant percentage of cats with cardiomyopathy do not have an auscultable murmur or gallop. Furthermore, in up to 25% of cats examined with heart murmurs in our}, number={3}, journal={Journal of Feline Medicine and Surgery}, publisher={SAGE Publications}, author={Bonagura, John D}, year={2016}, month={Jun}, pages={147–151} }
 @article{silveira_scansen_wassenaar_raterman_eleswarpu_jin_mo_white_bonagura_kolipaka_2016, title={Quantification of myocardial stiffness using magnetic resonance elastography in right ventricular hypertrophy: Initial feasibility in dogs}, volume={34}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84952780049&partnerID=MN8TOARS}, DOI={10.1016/j.mri.2015.10.001}, abstractNote={Myocardial stiffness is an important determinant of cardiac function and is currently invasively and indirectly assessed by catheter angiography. This study aims to demonstrate the feasibility of quantifying right ventricular (RV) stiffness noninvasively using cardiac magnetic resonance elastography (CMRE) in dogs with severe congenital pulmonary valve stenosis (PVS) causing RV hypertrophy, and compare it to remote myocardium in the left ventricle (LV). Additionally, correlations between stiffness and selected pathophysiologic indicators from transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging were explored. In-vivo CMRE was performed on nine dogs presenting severe congenital PVS using a 1.5 T MRI scanner. T1-MOLLI, T2-prepared-bSSFP, gated-cine GRE-MRE and LGE (PSIR) sequences were used to acquire a basal short-axis slice. RV and LV-free-wall (FW) stiffness measurements were compared against each other and also correlated to ventricular mass, RV and LV FW thickness, T1 and T2 relaxation times, and extracellular volume fraction (ECV). Peak transpulmonary pressure gradient and myocardial strain were also acquired on eight dogs by TTE and correlated to RV-FW systolic stiffness. Potential correlations were evaluated by Spearman's rho (rs). RV-FW stiffness was found to be significantly higher than the LV-FW stiffness both during end-systole (ES) (p = 0.002) and end-diastole (ED) (p = 0.029). Significant correlations were observed between RV-FW ES and LV-FW ED stiffness versus ECV (rs =0.75; p-value = 0.05). Non-significant moderate correlations were found between LV-FW ES (rs = 0.54) and RV-FW ED (rs = 0.61) stiffness versus ECV. Furthermore, non-significant correlations were found between RV or LV-FW stiffness and the remaining variables (rs < 0.54; p-value > 0.05). This study demonstrates the feasibility of determining RV stiffness. The positive correlations between stiffness and ECV might indicate some interdependence between stiffness and myocardial extracellular matrix alterations. However, further studies are warranted to validate our initial observations.}, number={1}, journal={Magnetic Resonance Imaging}, author={Silveira, J.S. and Scansen, B.A. and Wassenaar, P.A. and Raterman, B. and Eleswarpu, C. and Jin, N. and Mo, X. and White, R.D. and Bonagura, J.D. and Kolipaka, A.}, year={2016}, pages={26–34} }
 @article{pouchelon_atkins_bussadori_oyama_vaden_bonagura_chetboul_cowgill_elliot_francey_et al._2015, title={Cardiovascular-renal axis disorders in the domestic dog and cat: a veterinary consensus statement}, volume={56}, ISSN={["1748-5827"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84940504868&partnerID=MN8TOARS}, DOI={10.1111/jsap.12387}, abstractNote={There is a growing understanding of the complexity of interplay between renal and cardiovascular systems in both health and disease. The medical profession has adopted the term "cardiorenal syndrome" (CRS) to describe the pathophysiological relationship between the kidney and heart in disease. CRS has yet to be formally defined and described by the veterinary profession and its existence and importance in dogs and cats warrant investigation. The CRS Consensus Group, comprising nine veterinary cardiologists and seven nephrologists from Europe and North America, sought to achieve consensus around the definition, pathophysiology, diagnosis and management of dogs and cats with "cardiovascular-renal disorders" (CvRD). To this end, the Delphi formal methodology for defining/building consensus and defining guidelines was utilised.Following a literature review, 13 candidate statements regarding CvRD in dogs and cats were tested for consensus, using a modified Delphi method. As a new area of interest, well-designed studies, specific to CRS/CvRD, are lacking, particularly in dogs and cats. Hence, while scientific justification of all the recommendations was sought and used when available, recommendations were largely reliant on theory, expert opinion, small clinical studies and extrapolation from data derived from other species.Of the 13 statements, 11 achieved consensus and 2 did not. The modified Delphi approach worked well to achieve consensus in an objective manner and to develop initial guidelines for CvRD.The resultant manuscript describes consensus statements for the definition, classification, diagnosis and management strategies for veterinary patients with CvRD, with an emphasis on the pathological interplay between the two organ systems. By formulating consensus statements regarding CvRD in veterinary medicine, the authors hope to stimulate interest in and advancement of the understanding and management of CvRD in dogs and cats. The use of a formalised method for consensus and guideline development should be considered for other topics in veterinary medicine.}, number={9}, journal={JOURNAL OF SMALL ANIMAL PRACTICE}, author={Pouchelon, J. L. and Atkins, C. E. and Bussadori, C. and Oyama, M. A. and Vaden, S. L. and Bonagura, J. D. and Chetboul, V. and Cowgill, L. D. and Elliot, J. and Francey, T. and et al.}, year={2015}, month={Sep}, pages={537–552} }
 @article{depenbrock_visser_kohnken_russell_simpson_bonagura_2015, title={Congenital isolated cleft mitral valve leaflet and apical muscular ventricular septal defect in a Holstein calf}, volume={17}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85027928840&partnerID=MN8TOARS}, DOI={10.1016/j.jvc.2015.03.003}, abstractNote={A 5-week-old Holstein heifer calf presented for emergency treatment of signs referable to gastrointestinal disease and hypovolemic shock. Fluid resuscitation uncovered clinical signs of primary cardiac disease and echocardiography revealed multiple congenital cardiac defects. Malformations included a cleft anterior mitral valve leaflet resembling an isolated cleft mitral valve and an apically-located muscular ventricular septal defect. The echocardiographic and postmortem findings associated with these defects are presented and discussed in this report.}, number={3}, journal={Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology}, author={Depenbrock, S.M. and Visser, L.C. and Kohnken, R.A. and Russell, D.S. and Simpson, K.M. and Bonagura, J.D.}, year={2015}, pages={237–242} }
 @article{visser_scansen_brown_schober_bonagura_2015, title={Echocardiographic assessment of right ventricular systolic function in conscious healthy dogs following a single dose of pimobendan versus atenolol}, volume={17}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84968838481&partnerID=MN8TOARS}, DOI={10.1016/j.jvc.2015.04.001}, abstractNote={To quantify drug-induced changes in right ventricular (RV) systolic function after administration of pimobendan and atenolol.80 healthy privately-owned dogs.Using a prospective, blinded, fully-crossed study design with randomized drug administration, RV systolic function was determined twice at two time periods; before and 3 h after administration of pimobendan (0.25 mg/kg PO) or atenolol (1 mg/kg PO). Indices of RV systolic function included tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), pulsed-wave tissue Doppler-derived systolic myocardial velocity of the lateral tricuspid annulus (S'), and speckle-tracking-derived global longitudinal RV free wall strain and strain rate. The effect of treatment on percent change from baseline RV function was analyzed with a linear mixed model including the covariates heart rate, body weight, age, gender, drug sequence, and time period.All indices showed a significant (p < 0.0001) increase and decrease from baseline following pimobendan and atenolol, respectively. Significant differences from baseline were attributed to drug treatment (p < 0.0001); whereas, effects of other covariates were not significant. The greatest percent changes, but also highest variability, were observed for S' and strain rate (p < 0.0001). Post-atenolol, a significantly greater proportion of dogs exceeded the repeatability coefficient of variation for FAC and S' compared to TAPSE (p ≤ 0.007).Echocardiographic indices in healthy dogs tracked expected changes in RV systolic function following pimobendan and atenolol and warrant study in dogs with cardiovascular disease.}, number={3}, journal={Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology}, author={Visser, L.C. and Scansen, B.A. and Brown, N.V. and Schober, K.E. and Bonagura, J.D.}, year={2015}, pages={161–172} }
 @article{visser_scansen_schober_bonagura_2015, title={Echocardiographic assessment of right ventricular systolic function in conscious healthy dogs: Repeatability and reference intervals}, volume={17}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84931009616&partnerID=MN8TOARS}, DOI={10.1016/j.jvc.2014.10.003}, abstractNote={To determine the feasibility, repeatability, intra- and interobserver variability, and reference intervals for 5 echocardiographic indices of right ventricular (RV) systolic function: tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), pulsed wave tissue Doppler imaging-derived systolic myocardial velocity of the lateral tricuspid annulus (S'), and speckle-tracking echocardiography-derived global longitudinal RV free wall strain and strain rate. To explore statistical relationships between RV systolic function and age, gender, heart rate, and bodyweight.80 healthy adult dogs.Dogs underwent 2 echocardiographic examinations. Repeatability and intra-observer and inter-observer measurement variability were quantified by average coefficient of variation (CV). Relationships between RV function and age, heart rate and bodyweight were estimated by regression analysis.All indices were acquired with clinically acceptable repeatability and intra- and inter-observer variability (CVs < 10%). No differences were identified between male and female dogs. Allometric scaling by bodyweight demonstrated significant, clinically relevant correlations between RV function and bodyweight (all p ≤ 0.001) as follows: TAPSE - strong positive correlation (r(2) = 0.75); S' - moderate positive correlation (r(2) = 0.31); strain rate - moderate negative correlation (r(2) = 0.44); FAC and strain - weak negative correlations (r(2) = 0.22 and 0.14, respectively). Strain rate and FAC were positively correlated with heart rate (r(2) = 0.35 and 0.31, respectively). Allometric scaling generated bodyweight-based reference intervals for these RV systolic function indices.Echocardiographic indices of RV systolic function are feasible to obtain, repeatable, and affected by bodyweight. Studies of these indices in dogs with cardiovascular disease are needed.}, number={2}, journal={Journal of Veterinary Cardiology}, author={Visser, L.C. and Scansen, B.A. and Schober, K.E. and Bonagura, J.D.}, year={2015}, pages={83–96} }
 @article{bonagura_fuentes_2015, title={Echocardiography}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84948657570&partnerID=MN8TOARS}, DOI={10.1016/b978-1-4160-4867-1.00008-8}, journal={Small Animal Diagnostic Ultrasound}, publisher={Elsevier}, author={Bonagura, John D. and Fuentes, Virginia Luis}, year={2015}, pages={217–331} }
 @article{durham_scansen_bonagura_schober_cheatham_cheatham_2015, title={Iatrogenic embolization and transcatheter retrieval of a ventricular septal defect occluder in a dog}, volume={17}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84959367387&partnerID=MN8TOARS}, DOI={10.1016/j.jvc.2015.08.003}, abstractNote={A 7-month-old Irish Setter underwent transcatheter therapy of a muscular ventricular septal defect (VSD) and pulmonary valve stenosis. Standard devices for muscular VSD closure could not span the interventricular septum due to right ventricular hypertrophy, and an Amplatzer post-infarction muscular VSD occluder with a wider waist was successfully implanted. Following VSD closure, inflation of the balloon dilation catheter during balloon pulmonary valvuloplasty resulted in iatrogenic embolization of the VSD occluder to the left ventricular outflow tract. Retrieval and reimplantation of the device was achieved using a snare catheter. This report describes a potential complication and management during intracardiac device implantation in a dog. Additionally, the case illustrates that the Amplatzer post-infarction muscular VSD occluder holds potential value in animals with a hypertrophied interventricular septum that cannot be spanned using a conventional device.}, number={4}, journal={Journal of Veterinary Cardiology}, author={Durham, J.A. and Scansen, B.A. and Bonagura, J.D. and Schober, K.E. and Cheatham, S.L. and Cheatham, J.P.}, year={2015}, pages={304–313} }
 @article{ong_2015, title={Kirk's current veterinary therapy XV. by JD Bonagura and DC Twedt. Saunders Elsevier, United States, 2013. 1456 pages. Price: A$153.93. ISBN 9781437726893.}, volume={93}, DOI={10.1111/avj.12264}, abstractNote={Australian Veterinary JournalVolume 93, Issue 3 p. 83-83 BOOK REVIEW Kirk's current veterinary therapy XV. by JD Bonagura and DC Twedt. Saunders Elsevier, United States, 2013. 1456 pages. Price: A$153.93. ISBN 9781437726893. R Ong, R OngSearch for more papers by this author R Ong, R OngSearch for more papers by this author First published: 24 February 2015 https://doi.org/10.1111/avj.12264Citations: 2 Dr Ryan Ong is currently an Emergency and Critical Care specialist at WAVES Veterinary Hospital. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume93, Issue3March 2015Pages 83-83 RelatedInformation}, number={3}, journal={Australian Veterinary Journal}, publisher={Wiley}, author={Ong, R}, year={2015}, month={Feb}, pages={83–83} }
 @article{scansen_schneider_bonagura_2015, title={Sequential segmental classification of feline congenital heart disease}, volume={17}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84954447270&partnerID=MN8TOARS}, DOI={10.1016/j.jvc.2015.04.005}, abstractNote={Feline congenital heart disease is less commonly encountered in veterinary medicine than acquired feline heart diseases such as cardiomyopathy. Understanding the wide spectrum of congenital cardiovascular disease demands a familiarity with a variety of lesions, occurring both in isolation and in combination, along with an appreciation of complex nomenclature and variable classification schemes. This review begins with an overview of congenital heart disease in the cat, including proposed etiologies and prevalence, examination approaches, and principles of therapy. Specific congenital defects are presented and organized by a sequential segmental classification with respect to their morphologic lesions. Highlights of diagnosis, treatment options, and prognosis are offered. It is hoped that this review will provide a framework for approaching congenital heart disease in the cat, and more broadly in other animal species based on the sequential segmental approach, which represents an adaptation of the common methodology used in children and adults with congenital heart disease.}, journal={Journal of Veterinary Cardiology}, author={Scansen, B.A. and Schneider, M. and Bonagura, J.D.}, year={2015}, pages={S10–S52} }
 @article{blass_schober_li_scansen_bonagura_2014, title={Acute effects of ivabradine on dynamic obstruction of the left ventricular outflow tract in cats with preclinical hypertrophic cardiomyopathy}, volume={28}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84899622247&partnerID=MN8TOARS}, DOI={10.1111/jvim.12331}, abstractNote={Background Ivabradine is a negative chronotropic drug with minimal effects on central hemodynamics. Its effect on dynamic obstruction of the left ventricular outflow tract ( LVOT ) in cats with hypertrophic cardiomyopathy ( HCM ) remains unknown. Hypothesis/Objectives Ivabradine reduces dynamic obstruction of the LVOT in cats with HCM . Animals Twenty‐eight client‐owned cats with preclinical HCM and dynamic LVOT obstruction. Methods Randomized, double‐blind, active‐control single dose study. Cats received a single dose of either ivabradine (0.3 mg/kg PO ) or atenolol (2 mg/kg PO ). Heart rate, echocardiographic variables, and systolic blood pressure ( SBP ) were recorded before and 3 hours after drug administration. Statistical comparisons were made using ANCOVA . Results Peak velocity in the LVOT was significantly decreased compared to baseline for both drugs; however, the effect was more prominent with atenolol (mean reduction 2.53 m/s; 95% CI 2.07–3.13 m/s) compared to ivabradine (mean reduction 0.32 m/s; 95% CI −0.04 to 0.71 m/s; P < .0001). Echocardiographic indices of systolic function were largely unchanged by ivabradine, but significantly reduced by atenolol. Conclusions and Clinical Importance A single dose of ivabradine decreases dynamic LVOT obstruction in cats with HCM , but the clinical effect is negligible and inferior compared to that achieved by atenolol.}, number={3}, journal={Journal of Veterinary Internal Medicine}, author={Blass, K.A. and Schober, K.E. and Li, X. and Scansen, B.A. and Bonagura, J.D.}, year={2014}, pages={838–846} }
 @article{scansen_vitt_chew_schober_bonagura_2014, title={Comparison of forelimb and hindlimb systolic blood pressures and proteinuria in healthy shetland sheepdogs}, volume={28}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84897623206&partnerID=MN8TOARS}, DOI={10.1111/jvim.12289}, abstractNote={Background The prevalence of systemic hypertension ( SHT ) in Shetland Sheepdogs has not been reported. Hypothesis/Objectives SHT is common in Shetland Sheepdogs and positively correlated with proteinuria. Measurements of forelimb and hindlimb systolic arterial pressure ( SAP ) are comparable. Animals Seventy‐two clinically healthy, client‐owned Shetland Sheepdogs. Methods Forelimb and hindlimb SAP were recorded by Doppler ultrasonography. Proteinuria was quantified by urine dipstick, microalbuminuria, and protein:creatinine ratio ( UPC ). The relationship of UPC , anxiety, age, weight, and heart rate with forelimb SAP was evaluated. Results The mean forelimb and hindlimb SAP were 132 ± 20 and 118 ± 20 mmHg, respectively. The SAP exceeded 160 mmHg in 9 dogs, suggesting 13% prevalence of SHT . Four dogs had a UPC above 0.5; 2 of these had forelimb SAP exceeding 160 mmHg. Correlation of forelimb and hindlimb SAP was poor ( r 2 = 0.09; P = .011). Bland–Altman plots revealed substantial bias (−14 mmHg) between limb measurements with clinically unacceptable 95% limits of agreement (−60 to 33 mmHg). There was no correlation between forelimb SAP and UPC ( P = .06) or anxiety level ( P = .49). Age ( P < .0001) and heart rate ( P = .038) were significant predictors of forelimb SAP ; weight ( P = .73) was not. Conclusions Prevalence of SHT was 13% and not correlated with proteinuria. Forelimb and hindlimb SAP were poorly correlated; therefore, trends in an individual animal should be monitored using the same measurement site. Additionally, values for Doppler SAP were determined in Shetland Sheepdogs.}, number={2}, journal={Journal of Veterinary Internal Medicine}, author={Scansen, B.A. and Vitt, J. and Chew, D.J. and Schober, K.E. and Bonagura, J.D.}, year={2014}, pages={277–283} }
 @article{visser_scansen_bonagura_2014, title={ECG of the month}, volume={245}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84902832297&partnerID=MN8TOARS}, DOI={10.2460/javma.245.1.52}, number={1}, journal={Journal of the American Veterinary Medical Association}, author={Visser, L.C. and Scansen, B.A. and Bonagura, J.D.}, year={2014}, pages={52–54} }
 @article{ben-amotz_bonagura_velayutham_hamlin_burns_adin_2014, title={Intraperitoneal bilirubin administration decreases infarct area in a rat coronary ischemia/reperfusion model}, volume={5 FEB}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84895478668&partnerID=MN8TOARS}, DOI={10.3389/fphys.2014.00053}, abstractNote={Bilirubin was previously considered a toxin byproduct of heme catabolism. However, a mounting body of evidence suggests that at physiological doses, bilirubin is a powerful antioxidant and anti-atherosclerotic agent. Recent clinical studies have shown that human beings with genetically-induced hyperbilirubinemia (Gilbert Syndrome) are protected against coronary heart disease. The purpose of this study was to investigate whether administration of exogenous bilirubin to normal rats would convey similar protective effects in an experimental model of coronary ischemia. We hypothesized that intraperitoneal bilirubin administration 1 h before injury would decrease infarct area and preserve left ventricular (LV) systolic function when compared to non-treated rats. Coronary ischemia was induced by temporary (30 min) ligation of the left anterior descending coronary artery in control or bilirubin treated rats, followed by a 1-h period of reperfusion. LV function was estimated by measurements of fractional shortening (FS) and fractional area shortening using echocardiography. LV function decreased in both experimental groups after ischemia and reperfusion, although in bilirubin-treated rats FS was less depressed during the period of ischemia (18.8 vs. 25.8%, p = 0.034). Infarct size was significantly reduced in the bilirubin treated group compared to the non-treated group (13.34 vs. 25.5%, p = 0.0067). Based on the results of this study, bilirubin supplementation appears to provide significant decrease in infarct size although protective effects on LV function were noted only during the period of ischemia. This result also suggests that lipid soluble antioxidant bilirubin prevents the oxidation of cardiolipin and decreases the infarct size in the heart during ischemia.}, journal={Frontiers in Physiology}, author={Ben-Amotz, R. and Bonagura, J. and Velayutham, M. and Hamlin, R. and Burns, P. and Adin, C.}, year={2014} }
 @article{reef_bonagura_buhl_mcgurrin_schwarzwald_loon_young_2014, title={Recommendations for management of equine athletes with cardiovascular abnormalities}, volume={28}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84899653368&partnerID=MN8TOARS}, DOI={10.1111/jvim.12340}, abstractNote={Murmurs and arrhythmias are commonly detected in equine athletes. Assessing the relevance of these cardiovascular abnormalities in the performance horse can be challenging. Determining the impact of a cardiovascular disorder on performance, life expectancy, horse and rider or driver safety relative to the owner's future expectations is paramount. A comprehensive assessment of the cardiovascular abnormality detected is essential to determine its severity and achieve these aims. This consensus statement presents a general approach to the assessment of cardiovascular abnormalities, followed by a discussion of the common murmurs and arrhythmias. The description, diagnosis, evaluation, and prognosis are considered for each cardiovascular abnormality. The recommendations presented herein are based on available literature and a consensus of the panelists. While the majority of horses with cardiovascular abnormalities have a useful performance life, periodic reexaminations are indicated for those with clinically relevant cardiovascular disease. Horses with pulmonary hypertension, CHF , or complex ventricular arrhythmias should not be ridden or driven.}, number={3}, journal={Journal of Veterinary Internal Medicine}, author={Reef, V.B. and Bonagura, J. and Buhl, R. and Mcgurrin, M.K.J. and Schwarzwald, C.C. and Loon, G. and Young, L.E.}, year={2014}, pages={749–761} }
 @article{blass_schober_bonagura_scansen_visser_lu_smith_ward_2013, title={Clinical evaluation of the 3M Littmann Electronic Stethoscope Model 3200 in 150 cats}, volume={15}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84884469856&partnerID=MN8TOARS}, DOI={10.1177/1098612X13485480}, abstractNote={Detection of murmurs and gallops may help to identify cats with heart disease. However, auscultatory findings may be subject to clinically relevant observer variation. The objective of this study was to evaluate an electronic stethoscope (ES) in cats. We hypothesized that the ES would perform at least as well as a conventional stethoscope (CS) in the detection of abnormal heart sounds. One hundred and fifty consecutive cats undergoing echocardiography were enrolled prospectively. Cats were ausculted with a CS (WA Tycos Harvey Elite) by two observers, and heart sounds were recorded digitally using an ES (3M Littmann Stethoscope Model 3200) for off-line analysis. Echocardiography was used as the clinical standard method for validation of auscultatory findings. Additionally, digital recordings (DRs) were assessed by eight independent observers with various levels of expertise, and compared using interclass correlation and Cohen's weighted kappa analyses. Using the CS, a heart murmur (n = 88 cats) or gallop sound (n = 17) was identified in 105 cats, whereas 45 cats lacked abnormal heart sounds. There was good total agreement (83-90%) between the two observers using the CS. In contrast, there was only moderate agreement (P <0.001) between results from the CS and the DRs for murmurs, and poor agreement for gallops. The CS was more sensitive compared with the DRs with regard to murmurs and gallops. Agreement among the eight observers was good-to-excellent for murmur detection (81%). In conclusion, DRs made with the ES are less sensitive but comparably specific to a CS at detecting abnormal heart sounds in cats.}, number={10}, journal={Journal of Feline Medicine and Surgery}, author={Blass, K.A. and Schober, K.E. and Bonagura, J.D. and Scansen, B.A. and Visser, L.C. and Lu, J. and Smith, D.N. and Ward, J.L.}, year={2013}, pages={893–900} }
 @article{karrasch_scansen_aarnes_hubbell_bonagura_2013, title={ECG of the month}, volume={243}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84885935222&partnerID=MN8TOARS}, DOI={10.2460/javma.243.9.1260}, number={9}, journal={Journal of the American Veterinary Medical Association}, author={Karrasch, N.M. and Scansen, B.A. and Aarnes, T.K. and Hubbell, J.A. and Bonagura, J.D.}, year={2013}, pages={1260–1262} }
 @article{schober_zientek_li_fuentes_bonagura_2013, title={Effect of treatment with atenolol on 5-year survival in cats with preclinical (asymptomatic) hypertrophic cardiomyopathy}, volume={15}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84878525058&partnerID=MN8TOARS}, DOI={10.1016/j.jvc.2013.03.003}, abstractNote={To investigate the effect of treatment with atenolol on 5-year survival in cats with preclinical hypertrophic cardiomyopathy (HCM). 63 Client-owned cats with preclinical HCM and 31 healthy control cats. Prospective, observational, open-label, clinical cohort study. Cats with HCM were diagnosed by echocardiography, treated with atenolol (6.25–12.5 mg q12h, PO; n = 42) or untreated (n = 21), and were observed for 5 years after enrollment. The study end point was death from any cause. Cats of similar body weight, age, gender, and breed without evidence of heart disease were studied concurrently and served as controls. During the observational period, 27 cats with HCM died; 14 (22%) due to cardiac disease and 13 (21%) due to non-cardiac disease. Ten control cats (32%) died of non-cardiac disease. There was no significant difference (P = 0.307) in all-cause mortality between control and HCM. Cardiac mortality was higher in cats with HCM compared to control cats (P = 0.005). There was no significant difference in all-cause mortality (P = 0.729) and cardiac mortality (P = 0.897) between cats with HCM treated or untreated with atenolol. Age and left atrial size at diagnosis were the only predictors of 5-year outcome. Our study failed to demonstrate an effect of atenolol on 5-year survival in cats with preclinical HCM.}, number={2}, journal={Journal of Veterinary Cardiology}, author={Schober, K.E. and Zientek, J. and Li, X. and Fuentes, V.L. and Bonagura, J.D.}, year={2013}, pages={93–104} }
 @article{riesen_schober_bonagura_carnes_2013, title={Myocardial expression of hyperpolarization-activated, cyclic nucleotide-gated proteins in healthy cats and cats with hypertrophic cardiomyopathy,Myokardiale Exprimierung von Hyperpolarisations-aktivierten, Zyklonukleotid-regulierten Proteinen bei gesunden Katzen und Katzen mit Hypertropher Kardiomyopathie}, volume={155}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84873432209&partnerID=MN8TOARS}, DOI={10.1024/0036-7281/a000431}, abstractNote={In this article the myocardial expression of different hyperpolarization-activated, cyclic nucleotide-gated (HCN) isoforms in myocardial tissue from healthy control cats and cats with hypertrophic cardiomyopathy (HCM) was evaluated. Myocardial tissue samples of the left ventricle of control cats (n = 12) and cats with HCM (n = 4) were collected. Expression of feline HCN was determined by immunoblot analysis using antibodies against HCN2 and HCN4. Optical densities of HCN bands were compared among groups by use of the Mann-Whitney Rank Sum test. HCN4 was reliably detected in myocardial tissue whereas HCN2 was not. HCN4 expression was significantly increased in left ventricular (LV) myocardial samples of cats with HCM (P = 0.036) compared to control cats. Results indicate that myocardial HCN4 expression can be evaluated in cats by immunoblot analysis and that HCN4 expression is upregulated in LV myocardial tissue of cats with HCM. The pathophysiological importance of HCN overexpression with regard to myocyte function and altered automaticity deserves further study.}, number={2}, journal={Schweizer Archiv fur Tierheilkunde}, author={Riesen, S.C. and Schober, K.E. and Bonagura, J.D. and Carnes, C.A.}, year={2013}, pages={143–147} }
 @article{riesen_schober_smith_otoni_li_bonagura_2012, title={Effects of ivabradine on heart rate and left ventricular function in healthy cats and cats with hypertrophic cardiomyopathy}, volume={73}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84863016466&partnerID=MN8TOARS}, DOI={10.2460/ajvr.73.2.202}, abstractNote={To evaluate the effects of the pacemaker funny current (I(f)) inhibitor ivabradine on heart rate (HR), left ventricular (LV) systolic and diastolic function, and left atrial performance in healthy cats and cats with hypertrophic cardiomyopathy (HCM).6 healthy cats and 6 cats with subclinical HCM.Anesthetized cats underwent cardiac catheterization and were studied over a range of hemodynamic states induced by treatment with esmolol (200 to 400 μg/kg/min, IV), esmolol and dobutamine (5 μg/kg/min, IV), ivabradine (0.3 mg/kg, IV), and ivabradine and dobutamine. Left ventricular systolic and diastolic function, cardiac output, and left atrial function were studied via catheter-based methods and echocardiography.Treatment with ivabradine resulted in a significant reduction of HR, rate-pressure product, and LV contractile function and a significant increase in LV end-diastolic pressure, LV end-diastolic wall stress, and LV relaxation time constant (tau) in cats with HCM. Concurrent administration of ivabradine and dobutamine resulted in a significant increase of LV contractility and lusitropy, with blunted chronotropic effects of the catecholamine. Left atrial performance was not significantly altered by ivabradine in cats with HCM. Regression analysis revealed an association between maximum rate of LV pressure rise and tau in cats with HCM.Ivabradine had significant effects on several cardiovascular variables in anesthetized cats with HCM. Studies in awake cats with HCM are needed to clinically validate these findings.}, number={2}, journal={American Journal of Veterinary Research}, author={Riesen, S.C. and Schober, K.E. and Smith, D.N. and Otoni, C.C. and Li, X. and Bonagura, J.D.}, year={2012}, pages={202–212} }
 @article{ward_schober_fuentes_bonagura_2012, title={Effects of sedation on echocardiographic variables of left atrial and left ventricular function in healthy cats}, volume={14}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84866763651&partnerID=MN8TOARS}, DOI={10.1177/1098612X12447729}, abstractNote={Although sedation is frequently used to facilitate patient compliance in feline echocardiography, the effects of sedative drugs on echocardiographic variables have been poorly documented. This study investigated the effects of two sedation protocols on echocardiographic indices in healthy cats, with special emphasis on the assessment of left atrial size and function, as well as left ventricular diastolic performance. Seven cats underwent echocardiography (transthoracic two-dimensional, spectral Doppler, color flow Doppler and tissue Doppler imaging) before and after sedation with both acepromazine (0.1 mg/kg IM) and butorphanol (0.25 mg/kg IM), or acepromazine (0.1 mg/kg IM), butorphanol (0.25 mg/kg IM) and ketamine (1.5 mg/kg IV). Heart rate increased significantly following acepromazine/butorphanol/ketamine (mean ± SD of increase, 40 ± 26 beats/min) and non-invasive systolic blood pressure decreased significantly following acepromazine/butorphanol (mean ± SD of decrease, 12 ± 19 mmHg). The majority of echocardiographic variables were not significantly different after sedation compared with baseline values. Both sedation protocols resulted in mildly decreased left ventricular end-diastolic dimension and mildly increased left ventricular end-diastolic wall thickness. This study therefore failed to demonstrate clinically meaningful effects of these sedation protocols on echocardiographic measurements, suggesting that sedation with acepromazine, butorphanol and/or ketamine can be used to facilitate echocardiography in healthy cats.}, number={10}, journal={Journal of Feline Medicine and Surgery}, author={Ward, J.L. and Schober, K.E. and Fuentes, V.L. and Bonagura, J.D.}, year={2012}, pages={678–685} }
 @article{riesen_schober_cervenec_bonagura_2012, title={Effects of treatment with ivabradine and atenolol on reproducibility of echocardiographic indices of left heart size and function in healthy cats}, volume={14}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84861624277&partnerID=MN8TOARS}, DOI={10.1016/j.jvc.2011.11.007}, abstractNote={Data on reproducibility of echocardiographic indices in cats are commonly derived from studies in healthy, non-treated animals. However, medical treatment may alter reproducibility of such data possibly influencing interpretation of results of clinical trials assessing the effects of drugs on cardiovascular function. The objectives were therefore to investigate the effects of ivabradine and atenolol on reproducibility of echocardiographic indices of left heart function.Eight healthy cats.Repeated echocardiographic examinations were performed by two observers in mildly sedated cats at baseline and after four weeks of treatment (Group 1, ivabradine 0.3 mg/kg q12 h PO, n = 4; Group 2, atenolol 6.25 mg/cat q12 h PO, n = 4) in a prospective, double-blind, randomized study. Test reliability was determined by estimating measurement variability, within-day interobserver variability, and between-day intraobserver variability of all echocardiographic indices. Variability was expressed as coefficient of variation (CV) and the absolute value below which the difference between two measurements lay with 95% probability. Effects of treatments on variability were compared using linear mixed effects models ANOVA and Fisher's exact test.Overall, CVs ranged from 0.5 to 50.6% at baseline, 0.5-45.5% after ivabradine, and 0.5-23.3% after atenolol. Reproducibility of all variables determined did neither improve nor worsen consistently after either treatment although atenolol exhibited a tendency toward higher reliability with none of the CVs exceeding 24% as compared to ivabradine.Treatment of healthy cats with either atenolol or ivabradine had only minor effects on reproducibility of echocardiographic data. Whether these findings can be extrapolated to cats with hypertrophic cardiomyopathy deserves further study.}, number={2}, journal={Journal of Veterinary Cardiology}, author={Riesen, S.C. and Schober, K.E. and Cervenec, R.M. and Bonagura, J.D.}, year={2012}, pages={323–332} }
 @inbook{bonagura_lehmkuhl_morais_2012, title={Fluid and Diuretic Therapy in Heart Failure}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84862140033&partnerID=MN8TOARS}, DOI={10.1016/B978-1-4377-0654-3.00028-7}, booktitle={Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice}, author={Bonagura, J.D. and Lehmkuhl, L.B. and Morais, H.}, year={2012}, pages={514–543} }
 @article{smith_bonagura_culwell_schober_2012, title={Left ventricular function quantified by myocardial strain imaging in small-breed dogs with chronic mitral regurgitation}, volume={14}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84862795539&partnerID=MN8TOARS}, DOI={10.1016/j.jvc.2011.11.002}, abstractNote={The presence of left ventricular (LV) systolic dysfunction may influence prognosis or therapy in dogs with chronic mitral regurgitation (MR). Assessment of LV function in MR by conventional echocardiography is confounded by altered ventricular loading. Myocardial deformation (strain) imaging might offer more sensitive estimates of LV function in this disease. Prospectively measure myocardial strain in dogs with asymptomatic MR compared to a control group. Forty healthy dogs (3.5–11.5 kg): 20 Controls; 20 dogs with MR and LV remodeling (Stage B2), were evaluated in this study. LV size and function were assessed in a short-axis plane. Segmental radial strain and strain rate and global circumferential strain were measured using a 2D echocardiographic speckle-tracking algorithm (GE EchoPAC). Groups were compared using Bonferroni t-tests. Influences of heart rate and body weight were explored with linear regression. The MR group had significantly greater mean values for heart rate, LV size, and LV systolic function. Specifically, LV diastolic diameter, diastole area, shortening fraction, averaged peak systolic and early diastolic radial strain, global circumferential strain, and averaged radial strain rate were significantly greater in the MR group (p < 0.015 to p < 0.001). Strain was unrelated to weight, but weakly correlated with heart rate. Similar to conventional indices, Stage B2 dogs with MR demonstrate hyperdynamic deformation in the short-axis plane. Short-axis strain variables measured by 2D speckle tracking are greater than for controls of similar age and weight. These results imply either preserved LV systolic function or that LV dysfunction is masked by altered ventricular loading.}, number={1}, journal={Journal of Veterinary Cardiology}, author={Smith, D.N. and Bonagura, J.D. and Culwell, N.M. and Schober, K.E.}, year={2012}, pages={231–242} }
 @article{stern_doreste_barnett_lahmers_baumwart_seino_bonagura_2012, title={Resolution of sustained narrow complex ventricular tachycardia and tachycardia-induced cardiomyopathy in a Quarter Horse following quinidine therapy}, volume={14}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84865516632&partnerID=MN8TOARS}, DOI={10.1016/j.jvc.2012.05.004}, abstractNote={Sustained narrow-QRS tachycardia of three months duration and left ventricular systolic dysfunction were identified in a fifteen-year-old Quarter Horse. No underlying cause for the tachyarrhythmia was found and no predisposing structural cardiac lesions were evident by echocardiography. Intravenous diltiazem and lidocaine were administered without achieving successful conversion of the arrhythmia. Oral quinidine therapy converted the tachyarrhythmia to sinus rhythm. Ventricular systolic dysfunction and chamber dilatation subsequently resolved. As with other species, echocardiographic features of dilated cardiomyopathy can be tachycardia-induced and may resolve following successful control of heart rate and rhythm.}, number={3}, journal={Journal of Veterinary Cardiology}, author={Stern, JA and Doreste, YR and Barnett, S and Lahmers, SM and Baumwart, RD and Seino, KK and Bonagura, JD}, year={2012}, pages={445–451} }
 @inbook{bonagura_2011, title={Cardiac auscultation}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84906192764&partnerID=MN8TOARS}, booktitle={Clinical Veterinary Advisor: The Horse}, author={Bonagura, J.D.}, year={2011}, pages={681–683} }
 @article{culwell_bonagura_schober_2011, title={Comparison of echocardiographic indices of myocardial strain with invasive measurements of left ventricular systolic function in anesthetized healthy dogs}, volume={72}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79955775456&partnerID=MN8TOARS}, DOI={10.2460/ajvr.72.5.650}, abstractNote={Abstract Objective —To compare echocardiographic indices of myocardial strain with invasive measurements of left ventricular (LV) systolic function in anesthetized healthy dogs. Animals —7 healthy dogs. Procedures —In each anesthetized dog, preload and inotropic conditions were manipulated sequentially to induce 6 hemodynamic states; in each state, longitudinal, radial, and global strains and strain rate (SR), derived via 2-D speckle-tracking echocardiography, were evaluated along with conventional echocardiographic indices of LV function and maximum rate of rise (first derivative) of LV systolic pressure (LV+dp/dt max ). Catheter-derived and echocardiographic data were acquired simultaneously. Partial and semipartial correlation coefficients were calculated to determine the correlation between LV+dp/dt max and each echocardiographic variable. Global longitudinal strain was compared with conventional echocardiographic indices via partial correlation analysis. Results —All myocardial segments could be analyzed in all dogs. Significant semipartial correlations were identified between conventional echocardiographic strain indices and LV+dp/dt max . Correlation coefficients for longitudinal deformation and global strain, segmental longitudinal strain, and segmental SR were −0.773, −0.562 to −0.786, and −0.777 to −0.875, respectively. Correlation coefficients for radial segments and strain or SR were 0.654 to 0.811 and 0.748 to 0.775, respectively. Correlation coefficients for traditional echocardiographic indices and LV+dp/dt max (−0.586 to 0.821) and semipartial correlation coefficients for global strain and echocardiographic indices of LV systolic function (−0.656 [shortening fraction], −0.726 [shortening area], and −0.744 [ejection fraction]) were also significant. Conclusions and Clinical Relevance —Results indicated that LV systolic function can be predicted by myocardial strain and SR derived via 2-D speckle-tracking echocardiographic analysis in anesthetized healthy dogs.}, number={5}, journal={American Journal of Veterinary Research}, author={Culwell, N.M. and Bonagura, J.D. and Schober, K.E.}, year={2011}, pages={650–660} }
 @article{riesen_schober_cervenec_bonagura_2011, title={Comparison of the effects of ivabradine and atenolol on heart rate and echocardiographic variables of left heart function in healthy cats}, volume={25}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79955521396&partnerID=MN8TOARS}, DOI={10.1111/j.1939-1676.2011.0705.x}, abstractNote={Background: Ivabradine is a novel negative chronotropic drug used for treatment of ischemic heart disease in people. Little is known about its effects and safety in cats. Hypothesis/Objectives: Ivabradine is not inferior to atenolol with regard to clinical tolerance, heart rate (HR) reduction, and effects on cardiac function in healthy, lightly sedated cats. Animals: Ten healthy laboratory cats. Methods: Physical examination, systolic blood pressure measurement, and transthoracic echocardiography were performed in all cats at baseline and after oral administration (4 weeks each) of ivabradine (0.3 mg/kg q12h) and atenolol (6.25 mg/cat q12h; 1.0–1.7 mg/kg) in a prospective, double‐blind, randomized, active‐control, fully crossed study. A priori noninferiority margins for the effects of ivabradine compared with atenolol were set at 50% ( f = 0.5) based on predicted clinical relevance, observer measurement variability, and in agreement with FDA guidelines. Variables were compared by use of 2‐way repeated measures ANOVA. Results: Ivabradine was clinically well tolerated with no adverse events observed. HR (ivabradine, P < .001; atenolol, P < .001; ivabradine versus atenolol, P = .721) and rate‐pressure product (RPP) (ivabradine, P < .001; atenolol, P = .001; ivabradine versus atenolol, P = .847) were not different between treatments. At the dosages used, ivabradine demonstrated more favorable effects than atenolol on echocardiographic indices of left ventricular (LV) systolic and diastolic function and left atrial performance. Conclusions and Clinical Importance: Ivabradine is not inferior to atenolol with regard to effects on HR, RPP, LV function, left atrial performance, and clinical tolerance. Clinical studies in cats with hypertrophic cardiomyopathy are needed to validate these findings.}, number={3}, journal={Journal of Veterinary Internal Medicine}, author={Riesen, S.C. and Schober, K.E. and Cervenec, R.M. and Bonagura, J.D.}, year={2011}, pages={469–476} }
 @inbook{bonagura_2011, title={Congenital heart disease}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84906128509&partnerID=MN8TOARS}, booktitle={Clinical Veterinary Advisor: The Horse}, author={Bonagura, J.D.}, year={2011}, pages={122–123} }
 @article{hassan talukder_yang_nishijima_chen_xie_mahamud_kalyanasundaram_bonagura_periasamy_zweier_2011, title={Detrimental effects of thyroid hormone analog DITPA in the mouse heart: Increased mortality with in vivo acute myocardial ischemia-reperfusion}, volume={300}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79551497054&partnerID=MN8TOARS}, DOI={10.1152/ajpheart.00514.2010}, abstractNote={There is emerging evidence that treatment with thyroid hormone (TH) can improve postischemic cardiac function. 3,5-Diiodothyropropionic acid (DITPA), a TH analog, has been proposed to be a safer therapeutic agent than TH because of its negligible effects on cardiac metabolism and heart rate. However, conflicting results have been reported for the cardiac effects of DITPA. Importantly, recent clinical trials demonstrated no symptomatic benefit in patients with DITPA despite some improved hemodynamic and metabolic parameters. To address these issues, dose-dependent effects of DITPA were investigated in mice for baseline cardiovascular effects and postischemic myocardial function and/or salvage. Mice were treated with subcutaneous DITPA at 0.937, 1.875, 3.75, or 7.5 mg·kg(-1)·day(-1) for 7 days, and the results were compared with untreated mice for ex vivo and/or in vivo myocardial ischemia-reperfusion (I/R). DITPA had no effects on baseline body temperature, body weight, or heart rate; however, it mildly increased blood pressure. In isolated hearts, baseline contractile function was significantly impaired in DITPA-pretreated mice; however, postischemic recovery was comparable between untreated and DITPA-treated groups. In vivo baseline cardiac parameters were significantly affected by DITPA, with increased ventricular dimensions and decreased contractile function. Importantly, DITPA-treated mice demonstrated high prevalence of fatal cardiac rhythm abnormalities during in vivo ischemia and/or reperfusion. There were no improvements in myocardial infarction and postischemic fractional shortening with DITPA. Myocardial sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), phospholamban (PLB), and heat shock protein (HSP) levels remained unchanged with DITPA treatment. Thus DITPA administration impairs baseline cardiac parameters in mice and can be fatal during in vivo acute myocardial I/R.}, number={2}, journal={American Journal of Physiology - Heart and Circulatory Physiology}, author={Hassan Talukder, M.A. and Yang, F. and Nishijima, Y. and Chen, C.-A. and Xie, L. and Mahamud, S.D. and Kalyanasundaram, A. and Bonagura, J.D. and Periasamy, M. and Zweier, J.L.}, year={2011} }
 @article{schober_hart_stern_li_samii_zekas_scansen_bonagura_2011, title={Effects of treatment on respiratory rate, serum natriuretic peptide concentration, and doppler echocardiographic indices of left ventricular filling pressure in dogs with congestive heart failure secondary to degenerative mitral valve disease and dilated cardiomyopathy}, volume={239}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-80051727431&partnerID=MN8TOARS}, DOI={10.2460/javma.239.4.468}, abstractNote={Abstract Objective —To evaluate the effects of treatment on respiratory rate, serum natriuretic peptide concentrations, and Doppler echocardiographic indices of left ventricular filling pressure in dogs with congestive heart failure (CHF) secondary to degenerative mitral valve disease (MVD) and dilated cardiomyopathy (DCM). Design —Prospective cohort study. Animals —63 client-owned dogs. Procedures —Physical examination, thoracic radiography, analysis of natriuretic peptide concentrations, and Doppler echocardiography were performed twice, at baseline (examination 1) and 5 to 14 days later (examination 2). Home monitoring of respiratory rate was performed by the owners between examinations. Results —In dogs with MVD, resolution of CHF was associated with a decrease in respiratory rate, serum N-terminal probrain natriuretic peptide (NT-proBNP) concentration, and diastolic functional class and an increase of the ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic lateral mitral annulus motion (E:Ea Lat). In dogs with DCM, resolution of CHF was associated with a decrease in respiratory rate and serum NT-proBNP concentration and significant changes in 7 Doppler echocardiographic variables, including a decrease of E:Ea Lat and the ratio of peak velocity of early diastolic transmitral flow to isovolumic relaxation time. Only respiratory rate predicted the presence of CHF at examination 2 with high accuracy. Conclusions and Clinical Relevance —Resolution of CHF was associated with predictable changes in respiratory rate, serum NT-proBNP concentration, and selected Doppler echocardiographic variables in dogs with DCM and MVD. Home monitoring of respiratory rate was simple and was the most useful in the assessment of successful treatment of CHF.}, number={4}, journal={Journal of the American Veterinary Medical Association}, author={Schober, Karsten E and Hart, Taye M and Stern, Joshua A and Li, Xiaobai and Samii, Valerie F and Zekas, Lisa J and Scansen, Brian A and Bonagura, John D}, year={2011}, pages={468–479} }
 @article{fox_rush_reynolds_defrancesco_keene_atkins_gordon_schober_bonagura_stepien_et al._2011, title={Multicenter Evaluation of Plasma N-Terminal Probrain Natriuretic Peptide (NT-pro BNP) as a Biochemical Screening Test for Asymptomatic (occult) Cardiomyopathy in Cats}, volume={25}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-80053080395&partnerID=MN8TOARS}, DOI={10.1111/j.1939-1676.2011.00776.x}, abstractNote={B-type natriuretic peptide concentrations reliably distinguish between cardiac and respiratory causes of dyspnea, but its utility to detect asymptomatic cats with occult cardiomyopathy (OCM) is unresolved.Determine whether plasma N terminal probrain natriuretic peptide (NT-proBNP) concentration can discriminate asymptomatic cats with OCM from normal cats, and whether NT-proBNP concentration correlates with clinical, biochemical, and echocardiographic parameters.One hundred and fourteen normal, healthy cats; 113 OCM cats.Prospective, multicenter, case-controlled study. NT-proBNP was prospectively measured and cardiac status was determined from history, physical examination, and M-mode/2D/Doppler echocardiography. Optimal cut-off values were derived using receiver operating characteristic (ROC) curve analysis.NT-proBNP was higher (median, interquartile range [25th and 75th percentiles]) in (1) OCM (186 pmol/L; 79, 478 pmol/L) versus normal (24 pmol/L; 24, 32 pmol/L) (P < .001); and (2) hypertrophic obstructive cardiomyopathy (396 pmol/L; 205, 685 pmol/L) versus hypertrophic cardiomyopathy (112 pmol/L; 48, 318 pmol/L) (P < .001). In OCM, NT-proBNP correlated (1) positively with LVPWd (ρ = 0.23; P = .01), LA/Ao ratio (ρ = 0.31; P < .001), LVs (ρ = 0.33; P < .001), and troponin-I (ρ = 0.64; P < .001), and (2) negatively with %FS (ρ = -0.27; P = .004). Area under ROC curve was 0.92; >46 pmol/L cut-off distinguished normal from OCM (91.2% specificity, 85.8% sensitivity); >99 pmol/L cut-off was 100% specific, 70.8% sensitive.Plasma NT-proBNP concentration reliably discriminated normal from OCM cats, and was associated with several echocardiographic markers of disease severity. Further studies are needed to assess test performance in unselected, general feline populations, and evaluate relationships between NT-proBNP concentrations and disease progression.}, number={5}, journal={Journal of Veterinary Internal Medicine}, author={Fox, P.R. and Rush, J.E. and Reynolds, C.A. and Defrancesco, T.C. and Keene, B.W. and Atkins, C.E. and Gordon, S.G. and Schober, K.E. and Bonagura, J.D. and Stepien, R.L. and et al.}, year={2011}, pages={1010–1016} }
 @article{cober_schober_buffington_li_riesen_bonagura_2011, title={Pharmacodynamic effects of ivabradine, a negative chronotropic agent, in healthy cats}, volume={13}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-82255179207&partnerID=MN8TOARS}, DOI={10.1016/j.jvc.2011.06.001}, abstractNote={To determine the pharmacodynamic effects of oral ivabradine in cats. Eight healthy, adult domestic short hair cats. Each cat underwent four study periods of 24 h, receiving either one dose of placebo or ivabradine (0.1 mg/kg, 0.3 mg/kg, and 0.5 mg/kg) in a single-blind randomized crossover study. Clinical tolerance was assessed hourly for the first 8 h, at 12 h, and at the end of the 24-h study period. Heart rate and blood pressure were monitored continuously for 18–24 h via radiotelemetry after each treatment. Response to stress (acoustic startle) was studied before (t = 0) and after treatment (t = 4 h). Statistical comparisons were made using a linear mixed models and 1-way and 2-way repeated measures ANOVA. Heart rate (min−1) decreased significantly (P < 0.05) in a dose-dependent manner with peak negative chronotropic effects observed 3 h after ivabradine (mean ± SD; placebo, 144 ± 20; ivabradine 0.1 mg/kg, 133 ± 22; ivabradine 0.3 mg/kg, 112 ± 20; and ivabradine 0.5 mg/kg, 104 ± 11). Heart rate (min−1) was still reduced (P < 0.05) 12 h after ivabradine (0.3 mg/kg; 128 ± 18 and 0.5 mg/kg; 124 ± 16) compared to placebo (141 ± 21). The tachycardic response to acoustic startle was significantly (P < 0.01) blunted at all 3 doses of ivabradine. Myocardial oxygen consumption estimated by the rate-pressure product was significantly reduced (P < 0.05) for all doses of ivabradine. No effect of ivabradine on systolic, diastolic, and mean blood pressure was identified and no clinically discernable side effects were observed. These findings indicate that a single oral dose of ivabradine predictably lowers heart rate, blunts the chronotropic response to stress, and is clinically well tolerated in healthy cats. This makes ivabradine potentially interesting in the treatment of feline heart disease where ischemia is of pathophysiologic importance.}, number={4}, journal={Journal of Veterinary Cardiology}, author={Cober, R.E. and Schober, K.E. and Buffington, T.C.A. and Li, X. and Riesen, S.C. and Bonagura, J.D.}, year={2011}, pages={231–242} }
 @article{fine_tobias_bonagura_2010, title={Cardiovascular manifestations of iatrogenic hyperthyroidism in two dogs}, volume={12}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77955925499&partnerID=MN8TOARS}, DOI={10.1016/j.jvc.2010.03.001}, abstractNote={Two dogs were diagnosed with iatrogenic thyrotoxicosis (1 definitive, 1 presumptive). Both showed physical examination findings of agitation, tachypnea, and tachycardia. Sinus tachycardia with supraventricular ectopy was diagnosed in one case, and syncope and atrial flutter was present in the other. Both dogs had concurrent cardiac disease that might have contributed to the severity of their clinical signs. Excessive thyroid hormone supplementation in humans causes supraventricular arrhythmias including sinus tachycardia, supraventricular tachycardia, atrial fibrillation, and atrial flutter. Clinical signs and rhythm abnormalities resolved in both dogs with resolution of the thyrotoxicosis.}, number={2}, journal={Journal of Veterinary Cardiology}, author={Fine, D.M. and Tobias, A.H. and Bonagura, J.D.}, year={2010}, pages={141–146} }
 @article{blissitt_bonagura_2010, title={Colour flow Doppler echocardiography in horses with cardiac murmurs}, volume={27}, DOI={10.1111/j.2042-3306.1995.tb04993.x}, abstractNote={Summary Thirty‐two horses with cardiac murmurs typical of tricuspid, mitral and aortic regurgitation were studied using colour flow Doppler echocardiography. The dimensions and duration of any regurgitant signals, recorded at the cardiac valve suspected as being the site of origin of the murmur, were measured. Results were compared with flow signals described at the valves of normal horses (Blissitt and Bonagura 1995). Horses with murmurs suggestive of tricuspid (n=8) and aortic (n=8) regurgitation showed larger regurgitant signals at the tricuspid and aortic valves respectively, than has been reported in normal horses. Horses with murmurs suggestive of mitral regurgitation (n=8) had a regurgitant signal of longer duration than occurs in normal horses, but the jets were not larger. Comparison of two groups of horses with low and high grade murmurs of tricuspid regurgitation, showed that horses with louder murmurs had significantly longer jets of larger area than those with low grade murmurs. This study demonstrates that colour flow Doppler echocardiography is a sensitive technique for the detection of valvular regurgitation in horses. However, quantification of jet size and duration are important for distinguishing physiological backflow which occurs in normal horses (Blissitt and Bonagura 1995) from valvular regurgitation associated with cardiac murmurs.}, number={S19}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={BLISSITT, KAREN J. and BONAGURA, J. D.}, year={2010}, month={Jun}, pages={82–85} }
 @article{blissitt_bonagura_2010, title={Colour flow Doppler echocardiography in normal horses}, volume={27}, DOI={10.1111/j.2042-3306.1995.tb04989.x}, abstractNote={Colour flow Doppler echocardiography is a technique that is used with two-dimensional (2-D) echocardiography to study blood flow patterns in the heart and blood vessels. This method was used to define normal flow patterns and to evaluate valvular function in 40 clinically normal Thoroughbred and Thoroughbred cross horses. Flow patterns from 10 standardised echocardiographic images were described in relation to anatomic landmarks and timing during the cardiac cycle. Consistent intracardiac flow patterns were identified in the normal horses. High velocity flow signals or regurgitant jets were recorded at the tricuspid (77.5%), mitral (67.5%), aortic (47.5%) and pulmonary valves (40%) in clinically normal horses. Most of these signals were transient, and many were associated with valve closure. This study demonstrates that colour flow Doppler echocardiography is a sensitive technique for the detection of intracardiac flow in horses. It will provide a basis by which to compare studies in horses suspected of having valvular heart disease.}, number={S19}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={BLISSITT, KAREN J. and BONAGURA, J. D.}, year={2010}, month={Jun}, pages={47–55} }
 @article{schwarzwald_stewart_morrison_bonagura_2010, title={Cor pulmonale in a horse with granulomatous pneumonia}, volume={18}, DOI={10.1111/j.2042-3292.2006.tb00442.x}, abstractNote={Equine Veterinary EducationVolume 18, Issue 4 p. 182-187 Cor pulmonale in a horse with granulomatous pneumonia C. C. Schwarzwald, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210, USA Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210, USASearch for more papers by this authorA. J. Stewart, Department of Veterinary Clinical Sciences, Auburn University, Auburn, Alabama 36849, USASearch for more papers by this authorC. D. Morrison, Department of Pathology, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210, USASearch for more papers by this authorJ. D. Bonagura, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210, USASearch for more papers by this author C. C. Schwarzwald, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210, USA Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210, USASearch for more papers by this authorA. J. Stewart, Department of Veterinary Clinical Sciences, Auburn University, Auburn, Alabama 36849, USASearch for more papers by this authorC. D. Morrison, Department of Pathology, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210, USASearch for more papers by this authorJ. D. Bonagura, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210, USASearch for more papers by this author First published: 05 January 2010 https://doi.org/10.1111/j.2042-3292.2006.tb00442.xCitations: 10 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Citing Literature Volume18, Issue4August 2006Pages 182-187 RelatedInformation}, number={4}, journal={Equine Veterinary Education}, publisher={Wiley}, author={Schwarzwald, C. C. and Stewart, A. J. and Morrison, C. D. and Bonagura, J. D.}, year={2010}, month={Jan}, pages={182–187} }
 @article{schober_hart_stern_li_samii_zekas_scansen_bonagura_2010, title={Detection of Congestive Heart Failure in Dogs by Doppler Echocardiography}, volume={24}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-78349292918&partnerID=MN8TOARS}, DOI={10.1111/j.1939-1676.2010.0592.x}, abstractNote={Background: Echocardiographic prediction of congestive heart failure (CHF) in dogs has not been prospectively evaluated. Hypothesis: CHF can be predicted by Doppler echocardiographic (DE) variables of left ventricular (LV) filling in dogs with degenerative mitral valve disease (MVD) and dilated cardiomyopathy (DCM). Animals: Sixty-three client-owned dogs. Methods: Prospective clinical cohort study. Physical examination, thoracic radiography, analysis of natriuretic peptides, and transthoracic echocardiography were performed. Diagnosis of CHF was based upon clinical and radiographic findings. Presence or absence of CHF was predicted using receiver-operating characteristic (ROC) curve, multivariate logistic and stepwise regression, and best subsets analyses. Results: Presence of CHF secondary to MVD or DCM could best be predicted by E : isovolumic relaxation time (IVRT) (area under the ROC curve [AUC]=0.97, P < .001), respiration rate (AUC=0.94, P < .001), Diastolic Functional Class (AUC=0.93, P < .001), and a combination of Diastolic Functional Class, IVRT, and respiration rate (R2=0.80, P < .001) or Diastolic Functional Class (AUC=1.00, P < .001), respiration rate (AUC=1.00, P < .001), and E : IVRT (AUC=0.99, P < .001), and a combination of Diastolic Functional Class and E : IVRT (R2=0.94, P < .001), respectively, whereas other variables including N-terminal pro-brain natriuretic peptide, E : Ea, and E : Vp were less useful. Conclusion and Clinical Importance: Various DE variables can be used to predict CHF in dogs with MVD and DCM. Determination of the clinical benefit of such variables in initiating, modulating, and assessing success of treatments for CHF needs further study.}, number={6}, journal={Journal of Veterinary Internal Medicine}, author={Schober, KE and Hart, TM and Stern, JA and Li, X and Samii, VF and Zekas, LJ and Scansen, BA and Bonagura, JD}, year={2010}, pages={1358–1368} }
 @article{bonagura_2010, title={Feline cardiomyopathies}, DOI={10.22233/9781905319534.25}, abstractNote={Genetic and idiopathic myocardial diseases are often termed primary cardiomyopathies. These include hypertrophic (HCM), dilated (DCM), restrictive (RCM), arrhythmogenic right ventricular (ARVC) and unclassified (UCM) cardiomyopathies, as well as myocarditis (endomyocarditis). Myocardial infarction is a poorly characterized disorder in cats, which causes regional or global ventricular dysfunction. Of these conditions, HCM is most common. Secondary myocardial diseases develop from defined disorders such as systemic hypertension, hyperthyroidism, taurine deficiency and growth hormone excess (acromegaly). Echocardiographic findings overlap between primary and secondary myocardial disorders, but these conditions should be distinguished as patient management and long-term prognoses can differ. The chapter addresses History; Physical examination; Diagnostic studies; Specific feline cardiomyopathies; and Treating complications of feline cardiomyopathies.}, journal={BSAVA Manual of Canine and Feline Cardiorespiratory Medicine}, publisher={British Small Animal Veterinary Association}, author={Bonagura, John D.}, year={2010}, month={Mar}, pages={220–236} }
 @article{kittleson_bonagura_2010, title={Letter to the Editor}, volume={24}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-78349288018&partnerID=MN8TOARS}, DOI={10.1111/j.1939-1676.2010.0622.x}, abstractNote={Dear Editor We wish to express our concerns about the study "Efficacy of Spironolactone on Survival in Dogs with Naturally Occurring Mitral Regurgitation Caused by Myxomatous Mitral Valve Disease" (Bernay, et al. JVIM 2010;24(2):331–341). As summarized by the authors, spironolactone has theoretical value for management of canine heart failure (HF) due to mitral regurgitation (MR). In this study, the outcomes with both spironolactone therapy and placebo (along with an ACE-inhibitor ± furosemide ± digoxin) were superior to previously published HF trials (such as QUEST) that evaluated diuretics (including spironolactone), ACE-inhibitors, and pimobendan.1 These findings surprised us; accordingly, we asked if other factors might explain this apparent benefit. We trust that the statistical analysis is expert and agree that differences are evident between groups (with wide confidence limits for benefits of spironolactone). However, we also believe the clinical relevance of these findings is diminished by the study design, event rate, patient withdrawals, and patient categorization with regard to HF. The study design is odd as it includes two separate "lead-in" trials of different durations based on initial administration of furosemide at entry. Some dogs were then entered into a long-term study for a total of 3 combined studies. We draw attention to the atypically low event rates for an HF study (Figs 2 and 3), where only 39 out of 212 dogs reached the combined endpoints of cardiac death, euthanasia because of HF (euphemistically labeled MR in the paper), or severe worsening of "HF" over a 14–15-month span. We were also concerned by the high withdrawal rates, where 94 of 212 dogs (44%) failed to complete the study for reasons unrelated to the defined endpoints. The key issue for us is whether the dogs were appropriately characterized with regard to HF. Although the term "HF" is not specified as an endpoint, the findings of "cardiac-related death, euthanasia because of MR, or severe worsening of MR" clearly implicate HF, not MR, as the cause for major events. Additionally, the dogs were classified as ISACHC class II (mild-to-moderate) or III (severe) HF, meaning mild-to-severe cardiogenic pulmonary edema should have been evident. Thus, we believe the study conclusions are predicated on a clinical and imaging diagnosis of HF caused by MR. However, clinical findings defining HF were imprecise with none of the signs used specific for HF. We would have expected entry criteria of increased respiratory rate at rest, moderate-to-severe left atrial enlargement, and caudodorsal pulmonary infiltrates typical of HF. Only mild cardiomegaly was required for study enrollment (VHS > 10.5) and radiographic evidence of pulmonary edema was not required. We fear that these inaccurate criteria may have been confounded by the different levels of experience in veterinarians enrolling cases (some were specialists; others practiced at first opinion clinics). The majority were placed in ISACHC class II by these investigators, a category in which dogs with MR often exhibit clinical signs (eg, cough) due to bronchial compression and primary airway diseases, conditions that frequently mimic HF. Also, furosemide is typically a critical background drug for HF trials, but in the 3-month lead in trial it was withheld for 5 days. We contend that dogs with cardiogenic pulmonary edema generally can't survive for long without furosemide; yet over half of the dogs were enrolled without it. This would have created an ethical dilemma if patients were actually symptomatic from HF and strongly suggests these dogs were never in HF. Unfortunately, we do not know the precise number of dogs receiving furosemide during the study, nor the average daily dosage for each group. Our contention that a large percentage of study dogs were not in HF is also supported by the low mortality rates and the regression hazard ratio showing decreased survival probability when furosemide was needed for management (ie, these were the patients that were actually in HF). We believe that had the entry data been independently reviewed by veterinary cardiologists to assure the dogs were actually in HF, that many subjects would have been excluded from this trial. We also carry reservations about the low number of major events producing flat Kaplan-Meier slopes compared with past trials. While a 55% reduction in the risk of cardiac morbidity-mortality seems impressive, we believe it may relate to the small number of events superimposed on study groups that are heterogeneous relative to HF. The authors admit these dogs were not as seriously affected as those of other drug trials. This prompts the question: if spironolactone did work, at what stage of disease was benefit observed? Based on the vagaries of these data, we do not believe this question has been answered for any stage of the disease. Finally, we are concerned that this is yet another pharmaceutical study conducted with the intent of bringing a drug to market, but leaving many questions in its wake. We are not suggesting a company-centered study is inferior; however, we do believe in the value of independent perspective for study design, investigator recruitment, raw data assessment, statistical analysis, and manuscript preparation. We appreciate that pharmaceutical companies exist to develop and market drugs; that clinical investigators want to study new treatments and publish those results; and that public funding for veterinary trials is minimal. In this environment, we consider the best clinical studies trials as those involving the sponsoring company in partnership with independent clinical experts, statisticians, and clinical monitors (when drugs are earmarked for regulatory review). We believe such collaborations can better address issues of clinical importance, minimize ambiguities related to study conclusions, and reduce potential conflicts of interest.2 Perhaps if the independent veterinary cardiologist and statistical consultant who coauthored this paper had been actively involved at the earliest stage of this study, it would be more conclusive. Thus, we respectfully dispute that a survival benefit of spironolactone in canine MR is proven. Our arguments are centered on (1) patient categorization, (2) definition of HF, (3) heterogeneity of MR severity and HF within groups, and (4) the low event rates relative to the high number of case withdrawals. We are uncertain which dogs if any did benefit from spironolactone. Thus, regardless of the current EU regulatory approval, we consider use of spironolactone in MR empirical. We also plead for better collaboration between pharmaceutical companies and independent investigators at every stage of clinical trials. We believe this should be a focus for regulatory agencies and our scientific journals. While we would be happy to be corrected—that spironolactone greatly improves outcomes in dogs with HF due to MR—we believe that conclusion would require a different study.}, number={6}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Kittleson, M.D. and Bonagura, J.D.}, year={2010}, month={Nov}, pages={1245–1246} }
 @article{nelson_drost_lerche_bonagura_2010, title={Noninvasive estimation of central venous pressure in anesthetized dogs by measurement of hepatic venous blood flow velocity and abdominal venous diameter}, volume={51}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77953144519&partnerID=MN8TOARS}, DOI={10.1111/j.1740-8261.2010.01668.x}, abstractNote={Determination of central venous pressure (CVP) is relevant to patients with right heart disease, hypovolemia, and following intravenous fluid therapy. We hypothesized that changes in CVP in dogs could be predicted by measurements of hepatic vein diameter, caudal vena cava (CVC) diameter, and hepatic venous flow velocities. Nine healthy American Foxhounds were anesthetized. Following baseline recordings, intravenous fluids were administered to increase CVP. Volume administration created treatment periods with CVP ranges of 5, 10, 15, 20, and 25 mm Hg. Flow velocities in the right medial hepatic vein were recorded using pulsed wave Doppler ultrasound. Hepatic vein, CVC, and aorta diameters were determined with B-mode ultrasound. Variables were compared across the treatment periods by ANOVA for repeated measures. Relationships between CVP, Doppler, and B-mode variables were evaluated using Spearman's rank correlations, multiple linear regression, and repeated measures linear regression. The a-, S- and v-wave velocities were augmented significantly with volume loading. The best part (semipartial) correlation coefficients predicting increasing CVP were identified with v-wave velocity (0.823), S-wave velocity (−0.800), CVC diameter (0.855), and hepatic vein diameter (0.815). Multiple linear regression indicated that CVP in this study could be predicted best by a combination of CVC and hepatic vein diameter and the v-wave velocity (r=0.928). Ultrasound imaging identified gallbladder and pancreatic edema consistently, likely related to acute volume loading. These findings may be applicable in the assessment of volume status, dogs with right heart disease, and during serial monitoring of dogs receiving fluid or diuretic therapy.}, number={3}, journal={Veterinary Radiology and Ultrasound}, author={Nelson, N.C. and Drost, W.T. and Lerche, P. and Bonagura, J.D.}, year={2010}, pages={313–323} }
 @article{blissitt_bonagura_2010, title={Pulsed wave Doppler echocardiography in normal horses}, volume={27}, DOI={10.1111/j.2042-3306.1995.tb04988.x}, abstractNote={Reference values were established for selected Doppler derived variables from a group of 40 normal Thoroughbred and Thoroughbred cross horses. Standard two-dimensional (2-D) images used for guiding the Doppler sampling site allowed accurate alignment with flow. Tricuspid inflow velocities during rapid filling (E) and atrial contraction (A) were significantly higher when recorded from a right parasternal angled view than from a right parasternal long-axis view. In 8 horses the tricuspid inflow peak A velocity was higher than the peak E velocity. The peak acceleration of blood flow was higher (P = 0.000) in the aorta (mean 8.01 m/s/s) than in the pulmonary artery (4.45 m/s/s). Significant differences were also noted in the pre-ejection period, ejection time and acceleration time between the 2 vessels. Horses with functional ejection murmurs had lower peak aortic acceleration and a longer acceleration time than horses without flow murmurs. Horses with filling murmurs over the left hemithorax had a significantly higher peak mitral E velocity than horses without such murmurs. Measurements from Doppler waveforms were repeatable and may prove useful in assessing ventricular function in this species.}, number={S19}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={BLISSITT, KAREN J. and BONAGURA, J. D.}, year={2010}, month={Jun}, pages={38–46} }
 @article{kittleson_bonagura_2010, title={Re: Efficacy of spironolactone on survival in dogs with naturally occurring mitral regurgitation caused by myxomatous mitral valve disease.}, volume={24}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79952279451&partnerID=MN8TOARS}, number={6}, journal={Journal of veterinary internal medicine / American College of Veterinary Internal Medicine}, author={Kittleson, M.D. and Bonagura, J.D.}, year={2010} }
 @article{bonagura_blissitt_2010, title={Review Article: Echocardiography}, volume={27}, DOI={10.1111/j.2042-3306.1995.tb04984.x}, abstractNote={Summary Echocardiography encompasses a number of specific imaging techniques. The two‐dimensional (2‐D) echocardiogram is used to identify lesions of the heart and great vessels, assess myocardial function and provide a template for guiding contrast echocardiography, colour‐coded Doppler echocardiography and spectral Doppler studies. M‐mode echocardiography is used to measure cardiac size and ventricular function and can be combined with contrast or colour‐coded Doppler studies for accurate timing of flow events. Pulsed wave and continuous wave Doppler echocardiography display the direction and velocity of red blood cells within the heart and circulation. Continuous wave Doppler studies are used to calculate pressure gradients in the circulation. Any of the Doppler techniques can be used to identify abnormal or high velocity flow responsible for pathologic heart murmurs. Each Doppler format is complementary to the others: colour‐coded Doppler is used to screen large areas for flow disturbances; pulsed wave Doppler can pinpoint regions of abnormal flow; and continuous wave Doppler quantifies the maximal velocities of blood flow across cardiac lesions. Echocardiographic studies are very useful for the diagnosis and assessment of horses with cardiac murmurs, arrhythmias, and poor exercise performance. A number of cardiac disorders can be evaluated by echocardiography, including: cardiac malformation, valvular heart disease, cardiomyopathy, bacterial endocarditis, pericardial effusion, and congestive heart failure. When combined with a careful clinical examination, exercise evaluation and results of electrocardiography, the echocardiogram provides the best overall clinical assessment of the equine heart.}, number={S19}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={BONAGURA, J. D. and BLISSITT, KAREN J.}, year={2010}, month={Jun}, pages={5–17} }
 @article{margiocco_scansen_bonagura_2009, title={Camelid Cardiology}, volume={25}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-65549111111&partnerID=MN8TOARS}, DOI={10.1016/j.cvfa.2009.03.009}, abstractNote={Cardiovascular disorders, although not thoroughly described in the literature, are frequently diagnosed in South American camelids, causing morbidity, mortality, and loss of production. Definitive confirmation concerning the heritability of cardiac defects in these species is lacking; however, this potential exists and should be taken into account when counseling breeders and owners. This article describes the diagnosis and treatment of cardiovascular diseases in llamas and alpacas and reviews the most recent literature. Unique aspects of the cardiovascular physiology in these species are also reviewed.}, number={2}, journal={Veterinary Clinics of North America - Food Animal Practice}, author={Margiocco, M.L. and Scansen, B.A. and Bonagura, J.D.}, year={2009}, pages={423–454} }
 @article{bonagura_schober_2009, title={Can ventricular function be assessed by echocardiography in chronic canine mitral valve disease?}, volume={50}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-70349217688&partnerID=MN8TOARS}, DOI={10.1111/j.1748-5827.2009.00803.x}, abstractNote={Mitral regurgitation (MR) related to chronic degenerative valvular disease is the most important cause of heart failure in dogs. Ultrasound examination of the heart can identify valve lesions, confirm the presence of valvular regurgitation, document cardiac remodeling, estimate intracardiac pressures, and quantify systolic ventricular function. These findings can influence prognosis or selection of medical therapy. Reductions in ventricular systolic function may be detected on serial echocardiographic examinations in some dogs with MR. However the changes in ventricular loading that accompany MR often complicate these measurements. For example, shortening and ejection fractions are often increased in severe MR, even in the setting of congestive heart failure. Echocardiography with Doppler is also used to assess ventricular diastolic function and filling pressures. This information helps predict the risk of congestive heart failure. However these findings are often rendered ambiguous by age‐related impairment of ventricular relaxation, elevations in left atrial pressure due to MR, and effects of volume overload on myocardial tissue velocities. These factors limit the usefulness of ventricular filling and tissue velocities, as well as derived ratios such as the E/E' ratio, for predicting congestive heart failure in MR. More advanced Doppler and tissue echocardiographic methods, as well as prospective clinical studies, are needed to reduce the ambiguity involved with assessment of ventricular function and filling pressures in the setting of MR.}, number={SUPPL. 1}, journal={Journal of Small Animal Practice}, author={Bonagura, J.D. and Schober, K.E.}, year={2009}, pages={12–24} }
 @article{evaluation of a commercial ultrasonographic hemodynamic recording system for the measurement of cardiac output in dogs_2009, volume={70}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-67651219038&partnerID=MN8TOARS}, DOI={10.2460/ajvr.70.7.862}, abstractNote={Abstract Objective —To evaluate the accuracy of a commercial ultrasonographic cardiac output (CO) monitoring system (UCOMS) in anesthetized Beagles as assessed by comparison with thermodilution CO (TDCO). Animals —8 healthy anesthetized Beagles. Procedures —Simultaneous UCOMS and TDCO measurements of CO were obtained during 4 hemodynamic states: baseline anesthesia (0.5% to 1.5% isoflurane), a higher depth of anesthesia (2% to 3.5% isoflurane) to yield a ≥ 15% reduction in systolic arterial blood pressure, IV infusion of colloidal solution to a mean right atrial pressure of ≥ 15 mm Hg, and IV infusion of dobutamine at 5 μg/kg/min. Measurements were obtained at 2 probe positions: the subxiphoid region and the right thoracic inlet. Correlation and agreement of results between methods were determined via linear regression analysis and Bland-Altman plots. Results —A significant positive correlation was detected between UCOMS andTDCO measurements obtained at the subxiphoid (R = 0.86) and thoracic inlet (R = 0.83) positions. Bland-Altman plots revealed minimal bias between methods (bias ± SD, −0.03 ± 0.73 L/min and −0.20 ± 0.80 L/min for subxiphoid and thoracic inlet measurements, respectively). However, the percentage error associated with UCOMS measurements made at the 2 positions was > 45%. Conclusions and Clinical Relevance —When compared with the results of TDCO, CO measured with the UCOMS exceeded commonly accepted limits of error in healthy dogs. The UCOMS was, however, able to track changes in CO across hemodynamic states. Additional research is needed to assess the usefulness of the UCOMS for monitoring CO in critically ill dogs.}, number={7}, journal={American Journal of Veterinary Research}, year={2009}, pages={862–868} }
 @misc{atkins_bonagura_ettinger_fox_gordon_haggstrom_hamlin_keene_luis-fuentes_stepien_2009, title={Guidelines for the Diagnosis and Treatment of Canine Chronic Valvular Heart Disease}, volume={23}, ISSN={["1939-1676"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-70350430448&partnerID=MN8TOARS}, DOI={10.1111/j.1939-1676.2009.0392.x}, abstractNote={This is the report of the American College of Veterinary Internal Medicine (ACVIM) Specialty of Cardiology consensus panel convened to formulate guidelines for the diagnosis and treatment of chronic valvular heart disease (CVHD, also known as endocardiosis and myxomatous valve degeneration) in dogs. It is estimated that approximately 10% of dogs presented to primary care veterinary practices have heart disease, and CVHD is the most common heart disease of dogs in many parts of the world, accounting for approximately 75% of canine cases of heart disease cases seen by veterinary practices in North America. CVHD most commonly affects the left atrioventricular or mitral valve, although in approximately 30% of cases the right atrioventricular (tricuspid) valve also is involved. The disease is approximately 1.5 times more common in males than in females. Its prevalence is also higher in smaller (<20 kg) dogs, although large breeds occasionally are affected.1 In small breed dogs, the disease generally is slowly but somewhat unpredictably progressive, with most dogs experiencing the onset of a recognizable murmur of mitral valve regurgitation years before the clinical onset of heart failure. When large breed dogs are affected by CVHD, the progression of the disease appears to be more rapid than that observed in small breed dogs.2 Cavalier King Charles Spaniels are predisposed to developing CVHD at a relatively young age, but the time course of their disease progression to heart failure does not appear to be markedly different from that of other small breed dogs except for the early age of onset.3,4 The cause of CVHD is unknown, but the disease appears to have an inherited component in some breeds studied.5,6 CVHD is characterized by changes in the cellular constituents as well as the intercellular matrix of the valve apparatus (including the valve leaflets and chordae tendineae).7,8 These changes involve both the collagen content and the alignment of collagen fibrils within the valve.9,10 Endothelial cell changes and subendothelial thickening also occur,11 although affected dogs do not appear to be at increased risk for arterial thromboembolism or infective endocarditis. Mitral valve prolapse is a common complication of myxomatous valve degeneration and represents a prominent feature of CVHD in some breeds.6,12 Progressive deformation of the valve structure eventually prevents effective coaptation and causes regurgitation (valve leakage). Progressive valvular regurgitation increases cardiac work, leading to ventricular remodeling (eccentric hypertrophy and intercellular matrix changes) and ventricular dysfunction. Abnormal numbers or types of mitogen receptors (eg, any of the subtypes of serotonin, endothelin, or angiotensin receptors) on fibroblast cell membranes in the valves of affected dogs may play a role in the pathophysiology of the valvular lesions.13 Systemic or local metabolic, neurohormonal or inflammatory mediators (eg, endogenous catecholamines and inflammatory cytokines) also may influence progression of the valve lesion or the subsequent myocardial remodeling and ventricular dysfunction that accompany long-standing, hemodynamically significant valvular regurgitation. However, these factors are poorly understood at this time.14 The prevalence of CVHD increases markedly with age in small breed dogs (with up to 85% showing some evidence of the lesion at necropsy by 13 years of age), but the presence of the pathologic lesion does not necessarily indicate that a dog will develop clinical signs of heart failure. Like the underlying cause of the disease, the factors that determine the progression of the lesion remain unknown, although age, left atrial size, and heart rate have been shown to predict outcomes.15,16 Heart failure is a general term that describes a clinical syndrome that can be caused by a variety of specific heart diseases, including CVHD. Heart failure from any cause is characterized by cardiac, hemodynamic, renal, neurohormonal, and cytokine abnormalities. The classification systems for heart failure most familiar to veterinarians are the modified New York Heart Association (NYHA)17 and International Small Animal Cardiac Health Council18 functional classification systems, both of which were designed to provide a framework for discussing and comparing the clinical signs of patients in heart failure. These functional classification systems vary in their details, but both serve as semiquantitative schemes for judging the severity of a patient's clinical signs. Such categorization aids in teaching therapeutic protocols and constitutes a basis for stratification of subjects in clinical trials. The modified NYHA functional classification of heart failure can be summarized as follows: Class I describes patients with asymptomatic heart disease (eg, CVHD is present, but no clinical signs are evident even with exercise). Class II describes patients with heart disease that causes clinical signs only during strenuous exercise. Class III describes patients with heart disease that causes clinical signs with routine daily activities or mild exercise. Class IV describes patients with heart disease that causes severe clinical signs even at rest. Functional classification systems share a common problem in that they are based on relatively subjective assessments of clinical signs that can change frequently and dramatically over short periods of time. Furthermore, treatments may not differ substantially across the functional classes. A newer classification system that might more objectively categorize patients in the course of their heart disease has been developed, and this scheme was used by the panel for consensus recommendations. The goal was to link severity of signs to appropriate treatments at each stage of illness. In formulating these guidelines, the consensus panel adapted the 2001 American College of Cardiology/American Heart Association classification system for the treatment of heart disease and failure in human patients to the management of canine CVHD.19 In this approach, patients are expected to advance from 1 stage to the next unless progression of the disease is altered by treatment. The classification system presented below and used in these guidelines is meant to complement, not replace, functional classification systems. The new system describes 4 basic stages of heart disease and failure: Stage A identifies patients at high risk for developing heart disease but that currently have no identifiable structural disorder of the heart (eg, every Cavalier King Charles Spaniel without a heart murmur). Stage B identifies patients with structural heart disease (eg, the typical murmur of mitral valve regurgitation is present), but that have never developed clinical signs caused by heart failure. Because of important clinical implications for prognosis and treatment, the panel further subdivided Stage B into Stage B1 and B2. Stage B1 refers to asymptomatic patients that have no radiographic or echocardiographic evidence of cardiac remodeling in response to CVHD. Stage B2 refers to asymptomatic patients that have hemodynamically significant valve regurgitation, as evidenced by radiographic or echocardiographic findings of left-sided heart enlargement. Stage C denotes patients with past or current clinical signs of heart failure associated with structural heart disease. Because of important treatment differences between dogs with acute heart failure requiring hospital care and those with heart failure that can be treated on an outpatient basis, these issues have been addressed separately by the panel. Some animals presenting with heart failure for the 1st time may have severe clinical signs requiring aggressive therapy (eg, with additional afterload reducers or temporary ventilatory assistance) that more typically would be reserved for those with refractory disease (see Stage D). Stage D refers to patients with end-stage disease with clinical signs of heart failure caused by CVHD that are refractory to "standard therapy" (defined later in this document). Such patients require advanced or specialized treatment strategies in order to remain clinically comfortable with their disease. As with Stage C, the panel has distinguished between animals in Stage D that require acute, hospital-based therapy and those that can be managed as outpatients. This classification system emphasizes that there are risk factors and structural prerequisites for the development of heart failure in CVHD. The use of this classification system is meant to encourage veterinary clinicians to think about heart disease in a way analogous to the current clinical approach to cancer. This classification system is designed to aid in: Developing screening programs for the presence of CVHD in dogs known to be at risk. Identifying interventions that may (now or in the future) decrease the risk of disease development. Identifying asymptomatic dogs with CVHD early in the course of their disease, comparable to "in situ" cancer, so that they can perhaps be treated more effectively. Identifying symptomatic dogs with CVHD so that these patients can be treated medically and either potentially cured (interventionally or surgically) or managed with their chronic disease. Identify symptomatic dogs with advanced heart failure from CVHD and refractory to conventional therapy—these patients require aggressive or new treatment strategies or potentially hospice-type end-of-life care. In classifying dogs with CVHD according to their disease stage and clinical status and matching them with diagnostic, pharmacologic, and dietary treatment recommendations, the consensus panel considered both the quantity and quality of evidence available to inform the diagnostic and therapeutic decisions made in these patients. The heading "Consensus recommendation" preceding a diagnostic, therapeutic, or dietary recommendation indicates that the panelists were unanimous in their opinion that the combination of available clinical trial evidence, other published experimental or anecdotal evidence, clinical experience, and expert opinion indicate that the potential benefit of the approach under discussion clearly outweighs the potential risks to the patient and minimizes financial impact on the client. In situations in which the available evidence regarding the efficacy of a diagnostic or therapeutic maneuver was conflicting, weak, or absent and no consensus on a recommended course of action could be reached by the panelists based on the available evidence and their collective clinical experience, the panel's opinions and reasoning on clinically important issues are briefly summarized. These bulleted summary statements are grouped together and summarized under the heading "No consensus." The panel recognized that there is considerable variation in the scientific quality of the evidence available to support clinical decision making, and sought to include topically relevant references. Whereas the status of a particular recommendation (consensus versus no consensus) reflects the collective judgment of the panel on each question addressed, no attempt was made to assign a specific scientific grade or value to each included citation. Stage A—Dogs at high risk for development of heart failure, but without apparent structural abnormality (no heart murmur is heard) at the time of examination. Consensus recommendations: Small breed dogs, including breeds with known predisposition to develop CVHD (eg, Cavalier King Charles Spaniels, Dachshunds, Miniature and Toy Poodles) should undergo regular evaluations (yearly auscultation by the family veterinarian) as part of routine health care. Owners of breeding dogs or those at especially high risk, such as Cavalier King Charles Spaniels, may choose to participate in yearly screening events at dog shows or other events sponsored by their breed association or kennel club and conducted by board-certified cardiologists participating in an ACVIM-approved disease registry. Consensus recommendations: No drug therapy is recommended for any patient. No dietary therapy is recommended for any patient. Potential breeding stock should no longer be bred if mitral regurgitation (MR) is identified early, during their normal breeding age of <6–8 years. Stage B—These patients have a structural abnormality indicating the presence of CVHD, but have never had clinical signs of heart failure. These patients are generally recognized during a screening or routine health examination with a heart murmur typical of mitral valve insufficiency. Consensus recommendations: Thoracic radiography is recommended in all patients to assess the hemodynamic significance of the murmur and also to obtain baseline thoracic radiographs at a time when the patient is asymptomatic for CVHD. Blood pressure measurement is recommended for all patients. In small breed dogs with typical murmurs, echocardiography is recommended to answer specific questions regarding either cardiac chamber enlargement or the cause of the murmur if those questions are not answered adequately by auscultation and thoracic radiography. Echocardiography generally is indicated in larger breed dogs because the murmur of MR is more likely to be related to other causes (eg, dilated cardiomyopathy). Basic laboratory work (a minimum of hematocrit, total protein concentration, serum creatinine concentration, and urinalysis) is indicated in all patients. Because their prognosis and therapy may differ substantially, asymptomatic patients with murmurs of mitral valve insufficiency are further subcategorized into 2 groups based on the results of the above evaluation: Stage B1: Hemodynamically insignificant MR (defined as radiographically or echocardiographically normal or equivocally enlarged LA, LV, or both, with normal LV systolic function; normal vertebral heart score on radiography; normotensive, normal laboratory results). Therapy for Stage B1 (both pharmacologic and dietary) is identical for both small and large breed dogs. Consensus recommendations: Small and large breed dogs: No drug or dietary therapy is recommended. Re-evaluation is suggested by either radiography or echocardiography with Doppler studies in approximately 12 months (some panelists recommend more frequent follow-up in large dogs). Stage B2: Hemodynamically significant MR with cardiac remodeling (defined as clearly enlarged LA, LV, or both); normotensive. Therapy for Stage B2 (both pharmacologic and dietary) is controversial, and no consensus could be reached with currently available evidence. No consensus: Small breed dogs: Angiogensin converting enzyme inhibitor (ACEI): For patients with clinically relevant left atrial enlargement on either initial examination, or those in which the left atrium has increased in size dramatically on successive monitoring examinations, a majority of the panel members recommend initiation of therapy with an ACEI. Clinical trials addressing the efficacy of ACEI for the treatment of dogs in Stage B2 have had mixed results—either no effect or a small positive effect delaying the onset of congestive heart failure.20–22 A minority of the panel members recommend no therapy for asymptomatic animals pending further clinical trials to examine the efficacy of therapy in this setting. β blockers: For patients with clinically relevant left atrial enlargement on either initial examination, or when the left atrium has increased in size dramatically on successive monitoring examinations, a minority of the panel members recommend initiation of therapy with a low dosage of a β blocker, titrating to the highest tolerated dose over a period of approximately 1–2 months depending on the specific medication recommended. A majority of the panel members recommend no β-blocker therapy for asymptomatic animals pending further clinical trials to examine the efficacy of therapy in this setting. Clinical trials addressing the efficacy of β blockers for the treatment of dogs in Stage B2 are in progress. No other pharmacologic treatments were recommended in Stage B2 by a majority of panelists. A few panelists considered the use of the following medications for patients in Stage B2 under specific circumstances: pimobendan, digoxin, amlodipine, and spironolactone. The panel felt in general that these treatment strategies needed additional investigation into their efficacy and safety in this patient population before a consensus recommendation could be made. Dietary treatment was recommended by a majority of panelists in Stage B2, a minority of the panel recommended no dietary changes. Principles guiding dietary treatment at this stage include mild dietary sodium restriction and provision of a highly palatable diet with adequate protein and calories for maintaining optimal body condition. Larger breed dogs: Generally, panelists who recommended treatment in smaller breed dogs strengthened their recommendations promoting the use of both ACEI and β blockers in larger breed dogs in Stage B2. Dietary treatment recommendations for larger breed dogs were the same as those for small breeds, emphasizing mild sodium restriction and adequate protein and caloric intake if changes were recommended. Stage C—Patients have a structural abnormality and current or previous clinical signs of heart failure caused by CVHD. Stage C includes all patients that have had an episode of clinical heart failure. Such patients stay in this stage despite improvement of their clinical signs with standard therapy (even if their clinical signs resolve completely). Guidelines for standard pharmacotherapy are provided for both in-hospital (acute) management of heart failure and for home care (chronic) management of heart failure, as well as recommendations for chronic dietary therapy. Some patients that present in Stage C may have life-threatening clinical signs, and require more extensive acute therapy than is considered standard therapy. These acute care patients may share some medical management strategies with dogs that have progressed to Stage D (refractory heart failure, see below). In Stage C, heart failure secondary to CVHD, the panel did not make clinically relevant therapeutic distinctions between small and larger breed dogs for either acute or chronic medical management. For both Stages C and D (CVHD patients with symptomatic heart failure), the acute care of heart failure is focused on regulating the patient's hemodynamic status by monitoring (as well as possible under clinical circumstances) and pharmacologically optimizing preload, afterload, heart rate, and contractility to improve cardiac output, decrease the extent of mitral valve regurgitation if possible, and relieve clinical signs associated with either low cardiac output or excessively increased venous pressures (preload). The broad goals of chronic (home care) management are focused on maintaining these hemodynamic improvements to the extent possible, while providing additional treatments aimed at slowing progression, prolonging survival, decreasing clinical signs of congestive heart failure, enhancing exercise capacity, and otherwise improving quality life. Consensus recommendations: Because of the relatively high prevalence of chronic tracheobronchial disease in the same population at risk for CVHD, the presence of a typical left apical regurgitant murmur in a coughing dog does not necessarily mean that the clinical signs are the result of CVHD. A clinical database (including chest radiographs and preferably an echocardiogram and basic laboratory tests) must be obtained and examined carefully to accurately determine the cause of clinical signs in animals with CVHD. Serum N-terminal pro-B-type naturetic peptide (BNP) concentrations should become increasingly useful in determining the cause of clinical signs in dogs with CVHD. Although there is no doubt that, as a group, dogs with clinical signs caused by heart failure have higher serum BNP concentrations than those with clinical signs caused by primary pulmonary disease, the positive predictive value of any single BNP concentration, obtained by a commercially available test, has not been adequately characterized at the time of this writing (August 2009) to make a consensus recommendation with regard to BNP testing. The signalment and physical examination can be helpful in determining the pretest probability of heart failure as a cause of clinical signs in patients with CVHD. For example, obese dogs with no history of weight loss are less likely to be in heart failure secondary to CVHD; dogs with marked sinus arrhythmia and relatively slow heart rates also are less likely to have clinical signs attributable to CVHD. Most of these dogs are middle-aged or older, and it is always prudent to complete the database with a CBC, serum biochemical profile, and urinalysis, especially if therapy for CHF is anticipated. Consensus recommendations: Furosemide—The specific dosing of furosemide in a dog with CHF should be related to the severity of clinical signs and the response to initial therapy. Lower or higher doses (eg, 1–4 mg/kg) may be appropriate in specific cases. Repeated IV boluses or a constant rate IV infusion may be indicated for poorly responsive dogs. For life-threatening pulmonary edema (expectoration of froth associated with severe dyspnea; diffuse pulmonary opacity on thoracic radiographs; poor initial response to furosemide bolus with failure of dyspnea and respiratory rate to improve over 2 hours), furosemide is administered as a constant rate infusion (CRI) at a dose of 1 mg/kg/h after the initial bolus.23 Allow patient free access to water once diuresis has begun. Pimobendan, 0.25–0.3 mg/kg PO q12h—Although the clinical trial evidence supporting the chronic use of pimobendan in the management of Stage C heart failure from CVHD is stronger than for the acute situation, the recommendation to use pimobendan in acute heart failure therapy is strongly supported by hemodynamic and experimental evidence24–27 as well as the anecdotal experience of the panelists. Oxygen supplementation, if needed, can be administered via a humidity and temperature-controlled oxygen cage or incubator or via a nasal oxygen canula. Mechanical treatments (eg, abdominal paracentesis and thoracocentesis) are recommended to remove effusions judged sufficient to impair ventilation or cause respiratory distress. Provide optimal nursing care, including maintenance of an appropriate environmental temperature and humidity, increase in the head on pillows, and placement of sedated patients in sternal posture. Sedation—Anxiety associated with dyspnea should be treated. Narcotics, or a narcotic combined with an anxiolytic agent, are most often used by panelists. Butorphanol (0.2–0.25 mg/kg) administered IM or IV was the narcotic most often utilized for this purpose; combinations of buprenorphine (0.0075–0.01 mg/kg) and acepromazine (0.01–0.03 mg/kg IV, IM, or SQ) as well as other narcotics, including morphine and hydrocodone, also have been utilized. CRI of sodium nitroprusside for up to 48 hours is often useful for life-threatening, poorly responsive pulmonary edema (refer to Class D below for specific dosing recommendations). No consensus was reached on the following acute care Stage C issues: Care must be taken to monitor the blood pressure and respiratory response to narcotics and tranquililzers in the setting of acute heart failure. No specific treatment or dosage regimen was used by all panelists. ACEI (eg, enalapril 0.5 mg/kg PO q12h). Although treatment with ACEI is a consensus recommendation for chronic Stage C heart failure and a majority of panelists also treat acute heart failure with ACEI, the evidence supporting ACEI efficacy and safety in acute therapy when combined with furosemide and pimobendan is less clear. There is, however, clear evidence that the acute administration of enalapril plus furosemide in acute heart failure results in substantial improvement in pulmonary capillary wedge pressure when compared with the administration of furosemide alone. Nitroglycerin 2% ointment, approximately 1/2" paste per 10 kg body weight for 24–36 hours. Some panelists recommend administering the ointment in intervals (eg, 12 hours on, 12 hours off). Other panelists do not use nitroglycerin in this setting. Consensus recommendations: Continue PO furosemide administration to effect, commonly at a dosage of 2 mg/kg q12h. The daily furosemide dosage for dogs with CHF is wide and can be as low as 1–2 mg/kg PO q12h to 4–6 mg/kg PO q8h. The dosage must be titrated to maintain patient comfort and with attention to effects on renal function and electrolyte status. Chronic oral furosemide (doses ≥6 mg/kg q12h) needed to maintain patient comfort in the face of appropriate adjunct therapy indicates disease progression to Stage D. Continue or start ACEI (eg, enalapril 0.5 mg/kg, PO q12h) or equivalent dose of another ACEI if approved for use. The labeled dosage range of enalapril is 0.25–0.5 mg/kg PO q12h; most panelists treat at the upper end of this range. Measurement of serum creatinine and electrolyte concentrations 3–7 days after beginning an ACEI is recommended for animals with Stage C heart failure. Continue pimobendan (0.25–0.3 mg/kg PO q12h).28–30 Panelists recommend against starting a β blocker in the face of active clinical signs of heart failure (eg, cardiogenic pulmonary edema) caused by CVHD. None of the panelists routinely use nitroglycerin in the chronic treatment of Stage C heart failure. Participation in a structured, home-based extended care program to facilitate body weight, appetite, respiratory, and heart rate monitoring while providing client support to enhance medication compliance and dosage adjustments in patients with heart failure is encouraged. No consensus was reached regarding the following home-based (chronic) treatment strategies in Stage C: Spironolactone (0.25–2.0 mg/kg PO q12–24h) was recommended by a majority of panelists as an adjunct for the chronic therapy of dogs in Stage C heart failure. The primary purpose of spironolactone in this situation is thought to be aldosterone antagonism. No clinically relevant diuretic effect should be anticipated. This treatment now is approved in Europe at a dosage of 2 mg/kg/d. Digoxin (0.0025–0.005 mg/kg PO q12h) with target plasma concentration 8 hours postpill of 0.8–1.5 ng/mL. For the chronic management of Stage C heart failure, a majority of panelists recommended the addition of digoxin in cases complicated by persistent atrial fibrillation to slow the ventricular response rate. Some panelists also prescribe digoxin at this dosage for patients in Stage C heart failure in the absence of sustained supraventricular tachyarrhythmia, as long as no contraindication to digoxin is evident (eg, increased serum creatinine concentration, ventricular ectopy, concerns over owner compliance, chronic GI disease resulting in frequent or unpredictable bouts of vomiting or diarrhea). Once heart failure signs have resolved, a stable medication regimen has been instituted, and the patient is eating and apparently feeling well, a minority of panelists recommend attempting a low dose, slow up-titration regimen of a β blocker. There is no clinical trial evidence in dogs to support this recommendation. If prescribed, there is no consensus regarding which specific β blocker to use (carvedilol, atenolol, or metoprolol is the most frequently prescribed). The purpose of β blockade in this setting is related to potential long-term protective effects on myocardial function and remodeling. These effects have been demonstrated in some experimental animal models31 and in humans with heart failure, but not in clinical trials. The presence of atrial fibrillation strengthens the indication for β blockade (to slow the ventricular response to atrial fibrillation) for those panelists who recommended a β blocker. In patients taking a β blocker before the onset of Stage C heart failure, the majority of panelists continue β blockade; some panelists would consider dosage reduction if needed clinically because of clinical signs of low cardiac output, hypothermia, or bradycardia. Some panelists prefer administration of oral diltiazem (several formulations are available, some sustained release) for chronic heart rate control in atrial fibrillation. Some panelists find cough suppressants useful in occasional patients in Stage C heart failure from CVHD. Some panelists find bronchodilators useful in occasional patients in Stage C heart failure from CVHD. Cardiac cachexia is defined as the unintentional loss of >7.5% of the patient's normal, predisease weight, not including weight loss associated with the resolution of edema or the removal of body cavity effusions. Cachexia has substantial negative prognostic implications, and is much easier to prevent that to treat.32 Consensus recommendations: Maintain adequate calorie intake (maintenance calorie intake in Stage C should provide approximately 60 kcal/kg body weight) to minimize weight loss (specifically muscle mass loss) that often occurs in CHF. Specifically address and inquire about the occurrence of anorexia, and make efforts to treat any drug-induced or other identifiable causes of anorexia that occur. Record the accurate weight of the patient at every clinic visit, and investigate the cause of weight gain or loss. Ensure adequate protein intake and avoid low-protein diets designed to treat chronic kidney disease, unless severe concurrent renal failure is present. Modestly restrict sodium intake, taking into consideration sodium from all dietary sources (including dog food, treats, table food, and foods used to administer medications) and avoid any processed or other salted foods. Monitor serum potassium concentrations and supplement the diet with potassium from either natural or commercial sources if hypokalemia is identified. Hyperkalemia is relatively rare in patients treated for heart failure with diuretics, even in those concurrently receiving an ACEI in combination with spironolactone.33 Diets and foods with high potassium content should be avoided when hyperkalemia has been identified. No consensus was reached on the following dietary therapy for Stage C: Consider monitoring serum magnesium concentrations, especially as CHF progresses and in animals with arrhythmias. Supplement with magnesium in cases in which hypomagnesemia is identified. Consider supplementing with n-3 fatty acids, especially in dogs with decreased appetite, muscle mass loss, or arrhythmia.34 Stage D—Patients have clinical signs of failure refractory to standard treatment for Stage C heart failure from CVHD, as outlined above. Stage D heart failure patients therefore should be receiving the maximal recommended (or tolerated) dosage of furosemide, an ACEI, and pimobendan, as outlined in the Stage C guidelines above. Any indicated and tolerated antiarrhythmic medication, needed to maintain sinus rhythm (if possible) or regulate the ventricular response to atrial fibrillation in a heart rate range of 80–160/min, also should be used before a patient is considered refractory to standard therapy. Not surprisingly, there have been very few clinical trials addressing drug efficacy and safety in this patient population. This leaves cardiologists treating patients with heart failure refractory to conventional medical therapy with a perplexing variety of treatment options. Because of the relative lack of clinical trial evidence and the diverse clinical presentations of patients with end-stage heart failure, development of meaningful consensus guidelines regarding the timing and implementation of individual pharmacologic and dietary treatment strategies for Stage D patients proved difficult. As with Stage C, guidelines for drug treatment are provided for both in-hospital (acute) and for home care (chronic) management of heart failure, and recommendations for chronic dietary therapy are also given. Because Stage D heart failure patients are, by definition, refractory to the treatments for Stage C patients, defining refractory congestive heart failure involves the same diagnostic steps outlined for Stage C plus the finding of failure to respond to treatments outlined in the Stage C guidelines. Consensus recommendations: In the absence of severe renal insufficiency (ie, serum creatinine concentrations > 3 mg/dL), additional furosemide is administered IV as a bolus at a dosage of 2 mg/kg followed by either additional bolus doses, or a furosemide CRI at a dosage of 1 mg/kg/h until respiratory distress (rate and effort) has decreased, or for a maximum of 4 hours. As indicated above, the dosage or furosemide is a range and higher or lower doses may be appropriate for a given case. Continue to allow patient free access to water once diuresis has begun. Fluid removal (eg, abdominal paracentesis, thoracocentesis) as needed to relieve respiratory distress or discomfort. In addition to oxygen supplementation as in Stage C (above), mechanical ventilatory assistance may be useful to make the patient more comfortable, to allow time for medications35 to have an effect; and to provide time for left atrial dilatation to accommodate sudden increases in mitral valve regurgitant volume in patients with acute exacerbation of CVHD (eg, ruptured chordae tendinae with severe cardiogenic pulmonary edema) and impending respiratory failure. More vigorous afterload reduction in patients that can tolerate arterial vasodilation. Drugs potentially beneficial include sodium nitroprusside (starting at 0.5–1 μg/kg/min), hydralazine (0.5–2.0 mg/kg PO), or amlodipine (0.05–0.1 mg/kg PO). Direct vasodilators should be started at a low dosage and up-titrated hourly until adequate clinical improvement accompanied by a decrease of approximately 5–10% in systolic blood pressure is observed. These drugs are recommended in addition to an ACEI and pimobendan. The clinician should be mindful that any decline in blood pressure will also depend on specific vasodilator drug. For example, vasodilation effects are rapid onset with nitroprusside, but slower with amlodipine. Caution is warranted to avoid serious, prolonged hypotension (ie, monitor blood pressure and maintain systolic arterial blood pressure > 85 mmHg or mean arterial blood pressure > 60 mmHg. Serum creatinine concentration should be measured before and 24–72 hours after administration of these drugs. Patients in Stage D have life-threatening heart failure, and a trial of additional afterload reduction is warranted. The panel emphasized that because afterload reduction may increase cardiac output substantially in the setting of severe MR and heart failure, administration of an arterial dilator in this setting does not necessarily decrease blood pressure. No consensus was reached regarding the following acute care Stage D recommendations: Pimobendan dosage may be increased (off-label) to include a 3rd 0.3 mg/kg daily dose. Some panelists administer an additional dose of pimobendan on admission of Stage D patients with acute pulmonary edema. Because this dosage recommendation is outside of the FDA-approved labeling for pimobendan, this use of the drug should be explained to and approved by the client. In animals judged to be too sick to wait for the effects of oral afterload reduction or inotropic support (eg, pimobendan with or without hydralazine or amlodipine), nitroprusside (for afterload reduction in life threatening pulmonary edema) or dobutamine (for inotropic support of the hypotensive patient) must be administered by CRI. Both drugs can be administered at dosages of 0.5–1.0 μg/kg/min and up-titrated every 15–30 minutes to a maximum of approximately 10 μg/kg/min. These drugs, either separately or in combination, can be used for 12–48 hours to improve hemodynamic status and control refractory cardiogenic pulmonary edema. Continuous electrocardiographic and blood pressure monitoring is recommended to minimize the potential risks of this therapy. Sildenafil (1–2 mg/kg PO q12h) is used by a minority of panelists to treat acute exacerbations of Stage D heart failure caused by CVHD, even in the absence of diagnosed pulmonary hypertension. Bronchodilators are recommended as an adjunct therapy in treating cardiogenic pulmonary edema in hospitalized patients by a minority of panelists. Consensus recommendations: Furosemide dosage should be increased as needed to decrease pulmonary edema or body cavity effusions, if use is not limited by renal dysfunction (which generally should be monitored 12–48 hours after dosage increases). The specific strategy and magnitude of dosage increase (eg, same dose increased to 3 times per day versus 2 higher doses, substituting 1 SC dose for a PO dose q48h, or flexible SC dose supplementation based on body weight or girth measurements) varied widely among the panelists. Spironolactone, if not already started in Stage C, is indicated for chronic treatment of Stage D patients. β blockade generally should not be initiated at this stage unless clinical signs of heart failure can be controlled, as outlined in Stage C. No consensus was reached regarding the following chronic Stage D therapeutic recommendations: Hydrochlorthiazide was recommended by several panelists as adjunctive therapy with furosemide, utilizing various dosing schedules (including only intermittent use every 2nd–4th day). Some panelists warned of the risk of acute renal failure and marked electrolyte disturbances, based on personal experience. Pimobendan dosage is increased by some panelists to include a 3rd 0.3 mg/kg daily dose (off-label use, explanations and cautions apply as listed for in-hospital care, above). Digoxin, at the same (relatively low) dosages recommended by some panelists for Stage C heart failure, was recommended for treatment of atrial fibrillation for patients in Stage D, with the same cautions listed in Stage C above. Digoxin, at the same (relatively low) dosages recommended by some panelists for Stage C heart failure, also was recommended by a minority of panelists for all patients in Stage D in sinus rhythm, assuming no clear contraindication was present. Sildenafil (1–2 mg/kg PO q12h) is used by some panelists to treat Stage D heart failure caused by CVHD or to treat advanced CVHD complicated by pulmonary hypertension. The majority of panelists felt that β blockade initiated at an earlier stage of heart failure in CVHD should not be discontinued, but that dose reduction may be needed if shortness of breath could not be controlled by the addition of other medications or if bradycardia, hypotension, or both were present. β blockade still may be useful to decrease the ventricular response rate in atrial fibrillation after stabilization and digitalization. Cough suppressants are recommended by a minority of panelists to treat chronic, intractable cough in Stage D patients receiving home care. Bronchodilators are recommended by a minority of panelists to treat chronic, intractable coughing in Stage D patients receiving home careanelists. Consensus recommendations: All of the dietary considerations for Stage C (above) apply. In patients with refractory fluid accumulations, attempts should be made to further decrease dietary sodium intake if it can be done without compromising appetite or renal function.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Atkins, C. and Bonagura, J. and Ettinger, S. and Fox, P. and Gordon, S. and Haggstrom, J. and Hamlin, R. and Keene, B. and Luis-Fuentes, V. and Stepien, R.}, year={2009}, pages={1142–1150} }
 @article{schwarzwald_schober_berli_bonagura_2009, title={Left ventricular radial and circumferential wall motion analysis in horses using strain, strain rate, and displacement by 2D speckle tracking}, volume={23}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-67749132466&partnerID=MN8TOARS}, DOI={10.1111/j.1939-1676.2009.0321.x}, abstractNote={Noninvasive assessment of left-ventricular (LV) function is clinically relevant, but is incompletely studied in horses.To document the feasibility, describe the techniques, and determine the reliability of 2D speckle tracking (2DST) for characterization of LV radial and circumferential wall motion in horses.Three Standardbreds, 3 Thoroughbreds; age 8-14 years; body weight 517-606 kg.Observational study. Repeated 2-dimensional echocardiographic examinations were performed in unsedated horses by 2 observers and subsequently analyzed by 2DST. Test reliability was determined for segmental and for averaged 2DST indices (including strain, strain rate, displacement, and rotation) by estimating measurement variability, within-day interobserver variability, between-day interobserver variability, and between-day intraobserver variability. Variability was expressed as coefficient of variation (percent) and the absolute value below which the difference between 2 measurements will lie with 95% probability.2DST analyses were feasible in 16 of 18 echocardiographic studies. The automated tracking was accurate during systole but inaccurate during diastole. Reliability was higher for radial compared to circumferential measurements. For radial strain, radial systolic strain rate, and radial systolic displacement, the test-retest variabilities ranged between 2.4 and 33.1% for segmental and between 4.1 and 16.1% for averaged measurements.Systolic radial motion of the LV at the chordal level could be reliably characterized in horses by 2DST. Circumferential measurements were less reliable. Diastolic measurements were invalid because of inaccurate tracking. The clinical value of LV wall motion analysis by 2DST in horses requires further investigation.}, number={4}, journal={Journal of Veterinary Internal Medicine}, author={Schwarzwald, C.C. and Schober, K.E. and Berli, A.-S.J. and Bonagura, J.D.}, year={2009}, pages={890–900} }
 @article{schwarzwald_schober_bonagura_2009, title={Methods and reliability of tissue doppler imaging for assessment of left ventricular radial wall motion in horses}, volume={23}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-67449086622&partnerID=MN8TOARS}, DOI={10.1111/j.1939-1676.2009.0287.x}, abstractNote={Noninvasive assessment of left ventricular (LV) function is incompletely studied in horses.The goals of this study were to investigate the feasibility, techniques, and reliability of tissue Doppler imaging (TDI) for characterization of LV radial wall motion in healthy horses.Three Standardbreds, 3 Thoroughbreds; age 8-14 years; body weight 517-606 kg.Repeated echocardiographic examinations were performed by 2 observers in unsedated horses using TDI. Test reliability was determined by estimating measurement variability, within-day interobserver variability, and between-day interobserver and intraobserver variability of all echocardiographic variables. Variability was expressed as coefficient of variation (CV) and the absolute value below which the difference between 2 measurements will lie with 95% probability.Assessment of LV radial wall motion by TDI was feasible in all horses. Measurement variabilities were very low (CV < 5%) to low (CV 5-15%) for most variables. Within-day interobserver variability as well as between-day interobserver and intraobserver variabilities were low to moderate (CV 16-25%) for most variables. All pulsed-wave TDI variables of systolic LV function showed very low to low variability, whereas some of the variables of LV diastolic and LA function showed moderate to high (CV > 25%) variability. Pulsed-wave TDI variables appeared more reliable than color TDI variables.Measurement of TDI indices of LV function is feasible and reliable in adult Standardbred and Thoroughbred horses. The clinical relevance of LV function assessment by TDI remains to be determined.}, number={3}, journal={Journal of Veterinary Internal Medicine}, author={Schwarzwald, C.C. and Schober, K.E. and Bonagura, J.D.}, year={2009}, pages={643–652} }
 @inbook{schwarzwald_bonagura_muir_2009, title={The Cardiovascular System}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79954494697&partnerID=MN8TOARS}, DOI={10.1016/B978-1-4160-2326-5.00003-1}, booktitle={Equine Anesthesia}, publisher={Elsevier}, author={Schwarzwald, Colin C. and Bonagura, John D. and Muir, William W.}, year={2009}, pages={37–100} }
 @article{fox_oyama_reynolds_rush_defrancesco_keene_atkins_macdonald_schober_bonagura_et al._2009, title={Utility of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) to distinguish between congestive heart failure and non-cardiac causes of acute dyspnea in cats}, volume={11}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2008.12.001}, DOI={10.1016/j.jvc.2008.12.001}, abstractNote={Circulating plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration facilitates emergency diagnosis of congestive heart failure (CHF) in people. Its utility to discriminate between dyspneic cats with CHF vs. primary respiratory disease requires further assessment. Our objectives were to determine if NT-proBNP (1) differentiates dyspneic cats with CHF vs. primary respiratory disease; (2) increases with renal insufficiency; (3) correlates with left atrial dimension, radiographic cardiomegaly, and estimated left ventricular filling pressure (E/E(a)).NT-proBNP was measured in 167 dyspneic cats (66 primary respiratory disease, 101 CHF) to evaluate (1) relationship with clinical parameters; (2) ability to distinguish CHF from primary respiratory disease; (3) optimal cut-off values using receiver operating characteristic (ROC) curve analysis.NT-proBNP (1) was higher (median and inter-quartile [25th-75th] percentile) in CHF (754 pmol/L; 437, 1035 pmol/L) vs. primary respiratory disease (76.5 pmol/L; 24, 180 pmol/L) cohorts (P<0.001); (2) positively correlated in CHF cats with increased inter-ventricular septal end-diastolic thickness (rho=0.266; P=0.007) and LV free wall thickness (rho=0.218; P=0.027), but not with radiographic heart size, left atrial size, left ventricular dimensions, E/E(a) ratio, BUN, creatinine, or thyroxine; (3) distinguished dyspneic CHF cats from primary respiratory disease at 265 pmol/L cut-off value with 90.2% sensitivity, 87.9% specificity, 92% positive predictive value, and 85.3% negative predictive value (area under ROC curve, 0.94).NT-proBNP accurately discriminated CHF from respiratory disease causes of dyspnea.}, number={Supplement 1}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Fox, Philip R. and Oyama, Mark A. and Reynolds, Caryn and Rush, John E. and DeFrancesco, Terri C. and Keene, Bruce W. and Atkins, Clark E. and MacDonald, Kristin A. and Schober, Karsten E. and Bonagura, John D. and et al.}, year={2009}, month={May}, pages={S51–S61} }
 @article{scansen_schober_bonagura_smeak_2008, title={Acquired pulmonary artery stenosis in four dogs}, volume={232}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-43249115842&partnerID=MN8TOARS}, DOI={10.2460/javma.232.8.1172}, abstractNote={Abstract Case Description —4 dogs with acquired pulmonary artery stenosis (PAS) were examined for various clinical signs. One was a mixed-breed dog with congenital valvular PAS that subsequently developed peripheral PAS, one was a Golden Retriever with pulmonary valve fibrosarcoma, one was a Pembroke Welsh Corgi in which the left pulmonary artery had inadvertently been ligated during surgery for correction of patent ductus arteriosus, and one was a Boston Terrier with a heart-base mass compressing the pulmonary arteries. Clinical Findings —All 4 dogs were evaluated with 2-dimensional and Doppler echocardiography to characterize the nature and severity of the stenoses; other diagnostic tests were also performed. Treatment and Outcome —The mixed-breed dog with valvular and peripheral PAS was euthanized, surgical resection of the pulmonic valve mass was performed in the Golden Retriever, corrective surgery was performed on the Pembroke Welsh Corgi with left pulmonary artery ligation, and the Boston Terrier with the heart-base mass was managed medically. Clinical Relevance —Acquired PAS in dogs may manifest as a clinically silent heart murmur, syncope, or right-sided heart failure. The diagnosis is made on the basis of imaging findings, particularly results of 2-dimensional and Doppler echocardiography. Treatment may include surgical, interventional, or medical modalities and is targeted at resolving the inciting cause.}, number={8}, journal={Journal of the American Veterinary Medical Association}, author={Scansen, B.A. and Schober, K.E. and Bonagura, J.D. and Smeak, D.D.}, year={2008}, pages={1172–1180} }
 @article{bonagura_2008, title={Congenital Heart Disease}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882900280&partnerID=MN8TOARS}, DOI={10.1016/b978-1-4160-3949-5.50012-1}, journal={Handbook of Small Animal Practice}, publisher={Elsevier}, author={Bonagura, John D.}, year={2008}, pages={82–93} }
 @article{schober_bonagura_scansen_stern_ponzio_2008, title={Estimation of left ventricular filling pressure by use of Doppler echocardiography in healthy anesthetized dogs subjected to acute volume loading}, volume={69}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-49749119138&partnerID=MN8TOARS}, DOI={10.2460/ajvr.69.8.1034}, abstractNote={To identify Doppler echocardiographic (DE) variables that correlate with left ventricular filling pressure (LVFP).7 healthy dogs (1 to 3 years old).Dogs were anesthetized and instrumented to measure left atrial pressure (LAP), left ventricular pressures, and cardiac output. Nine DE variables of LVFP derived from diastolic time intervals, transmitral and pulmonary venous flow, and tissue Doppler images were measured over a range of hemodynamic states induced by volume loading and right atrial pacing. Associations between simultaneous invasive measures of LVFP and DE measures of LVFP were determined by use of regression analysis. Receiver operating characteristic analysis was used to predict increases in mean LAP on the basis of DE variables.Mean LAP was correlated with several DE variables: the ratio between peak velocity during early diastolic transmitral flow and left ventricular isovolumic relaxation time (peak E:IVRT) during sinus rhythm and during right atrial pacing, IVRT, the ratio between late diastolic transmitral flow velocity and pulmonary venous flow duration, and the interval between onset of early diastolic mitral annulus motion and onset of early diastolic transmitral flow. Cutoff values of 2.20 and 2.17, for peak E:IVRT in dogs with sinus rhythm and atrial pacing predicted increases in mean LAP (> or = 15 mm Hg) with sensitivities of 90% and 100% and specificities of 92% and 100%, respectively.Doppler echocardiography can be used to predict an increase in LVFP in healthy anesthetized dogs subjected to volume loading.}, number={8}, journal={American Journal of Veterinary Research}, author={Schober, Karsten E and Bonagura, John D and Scansen, Brian A and Stern, Joshua A and Ponzio, Nicole M}, year={2008}, pages={1034–1049} }
 @article{schwarzwald_hamlin_bonagura_nishijima_meadows_carnes_2007, title={Atrial, SA nodal, and AV nodal electrophysiology in standing horses: Normal findings and electrophysiologic effects of quinidine and diltiazem}, volume={21}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33847012195&partnerID=MN8TOARS}, DOI={10.1892/0891-6640(2007)21[166:ASNAAN]2.0.CO;2}, abstractNote={Background: Although atrial arrhythmias are clinically important in horses, atrial electrophysiology has been incompletely studied.Hypotheses: Standard electrophysiologic methods can be used to study drug effects in horses.Specifically, the effects of diltiazem on atrioventricular (AV) nodal conduction are rate-dependent and allow control of ventricular response rate during rapid atrial pacing in horses undergoing quinidine treatment.Animals: Fourteen healthy horses.Methods: Arterial blood pressure, surface electrocardiogram, and right atrial electrogram were recorded during sinus rhythm and during programmed electrical stimulation at baseline, after administration of quinidine gluconate (10 mg/kg IV over 30 minutes, n 5 7; and 12 mg/kg IV over 5 minutes followed by 5 mg/kg/h constant rate infusion for the remaining duration of the study, n 5 7), and after coadministration of diltiazem (0.125 mg/kg IV over 2 minutes repeated every 12 minutes to effect).Results: Quinidine significantly prolonged the atrial effective refractory period, shortened the functional refractory period (FRP) of the AV node, and increased the ventricular response rate during atrial pacing.Diltiazem increased the FRP, controlled ventricular rate in a rate-dependent manner, caused dose-dependent suppression of the sinoatrial node and produced a significant, but well tolerated decrease in blood pressure.Effective doses of diltiazem ranged from 0.125 to 1.125 mg/kg.Conclusions and Clinical Importance: Standard electrophysiologic techniques allow characterization of drug effects in standing horses.Diltiazem is effective for ventricular rate control in this pacing model of supraventricular tachycardia.The use of diltiazem for rate control in horses with atrial fibrillation merits further investigation.}, number={1}, journal={Journal of Veterinary Internal Medicine}, author={Schwarzwald, C.C. and Hamlin, R.L. and Bonagura, J.D. and Nishijima, Y. and Meadows, C. and Carnes, C.A.}, year={2007}, pages={166–175} }
 @article{chronic cardiac resynchronization therapy and reverse ventricular remodeling in a model of nonischemic cardiomyopathy_2007, volume={81}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-34548829906&partnerID=MN8TOARS}, DOI={10.1016/j.lfs.2007.08.022}, abstractNote={While cardiac resynchronization therapy (CRT) has been shown to reduce morbidity and mortality in heart failure (HF) patients, the fundamental mechanisms for the efficacy of CRT are poorly understood. The lack of understanding of these basic mechanisms represents a significant barrier to our understanding of the pathogenesis of HF and potential recovery mechanisms. Our purpose was to determine cellular mechanisms for the observed improvement in chronic HF after CRT. We used a canine model of chronic nonischemic cardiomyopathy. After 15 months, dogs were randomized to continued RV tachypacing (untreated HF) or CRT for an additional 9 months. Six minute walk tests, echocardiograms, and electrocardiograms were done to assess the functional response to therapy. Left ventricular (LV) midmyocardial myocytes were isolated to study electrophysiology and intracellular calcium regulation. Compared to untreated HF, CRT improved HF-induced increases in LV volumes, diameters and mass (p<0.05). CRT reversed HF-induced prolongations in LV myocyte repolarization (p<0.05) and normalized HF-induced depolarization (p<0.03) of the resting membrane potential. CRT improved HF-induced reductions in calcium (p<0.05). CRT did not attenuate the HF-induced increases in LV interstitial fibrosis. Using a translational approach in a chronic HF model, CRT significantly improved LV structure; this was accompanied by improved LV myocyte electrophysiology and calcium regulation. The beneficial effects of CRT may be attributable, in part, to improved LV myocyte function.}, number={14}, journal={Life Sciences}, year={2007}, pages={1152–1159} }
 @article{koffas_luis fuentes_boswood_connolly_brockman_bonagura_meurs_koplitz_baumwart_2007, title={Double chambered right ventricle in 9 cats}, volume={21}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33847076258&partnerID=MN8TOARS}, DOI={10.1892/0891-6640(2007)21[76:DCRVIC]2.0.CO;2}, abstractNote={Background: Double-chambered right ventricle (DCRV) is a frequently recognized cardiac congenital abnormality in humans.It has been described in dogs and in 1 cat.However systemic description of clinical and echocardiographic features of the disease in cats is currently lacking from the veterinary literature.Animals: Nine cats with DCRV are described.Results: The cats ranged from 4 months to 10 years of age.Eight cats at presentation were asymptomatic and 1 cat had chylothorax.In all cases echocardiography revealed abnormal fibromuscular bundles obstructing the mid-right ventricle, dividing the chamber into 2 compartments.The proximal right ventricular compartment was markedly hypertrophied, and right atrial dilation was usually present.The mean pressure gradient measured across the stenotic area was 130 6 50 mm Hg.Concurrent abnormalities included a ventricular septal defect (n 5 2); aortic malalignment, aortic insufficiency (n 5 1); and congenital peritoneal-pericardial diaphragmatic hernia (n 5 1).Two cats had systolic anterior motion of the mitral valve, one of which had concurrent left ventricular hypertrophy.Five cats have remained asymptomatic for a median period of 3.6 years (range, 3.3-5 years) and 3 cats have developed clinical signs associated with congestive heart failure (at 2, 3.3, and 9 years).One cat showed progressive lethargy and exercise intolerance and underwent partial ventriculectomy at the age of 2 years.This cat died during the operation with electromechanical dissociation.Conclusions: DCRV is a congenital cardiac abnormality that may be more common than previously recognized.}, number={1}, journal={Journal of Veterinary Internal Medicine}, author={Koffas, H. and Luis Fuentes, V. and Boswood, A. and Connolly, D.J. and Brockman, D.J. and Bonagura, J.D. and Meurs, K.M. and Koplitz, S. and Baumwart, R.}, year={2007}, pages={76–80} }
 @article{schwarzwald_schober_bonagura_2007, title={Echocardiographic evidence of left atrial mechanical dysfunction after conversion of atrial fibrillation to sinus rhythm in 5 horses}, volume={21}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-34547777966&partnerID=MN8TOARS}, DOI={10.1892/0891-6640(2007)21[820:EEOLAM]2.0.CO;2}, number={4}, journal={Journal of Veterinary Internal Medicine}, author={Schwarzwald, C.C. and Schober, K.E. and Bonagura, J.D.}, year={2007}, pages={820–827} }
 @article{muto_sargeant_tangkawattana_takeyasu_nishijima_bonagura_hoshijima_nakade_hosaka_faulkner_et al._2007, title={Intranuclear paracrystals observed in striated muscle specific LIM protein-deficient mouse cardiomyocytes}, volume={70}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33846110395&partnerID=MN8TOARS}, DOI={10.1002/jemt.20386}, abstractNote={A paracrystalline structure was observed within left ventricular cardiomyocyte nuclei of MLP(-/-) mice. The paracrystal possessed cross lines, approximately 8.0 micro m long and 0.3 micro m wide, with a slender spindle shape and a periodicity of 13 nm. Paracrystals were best observed along the longitudinal orientation of myofibrils and were detected in less than 10% of the nuclei observed. One dimension of the protein unit forming the paracrystal was 8.5 nm long. The electron density of the paracrystal appeared to be slightly higher than that of heterochromatin, suggesting that RNA-associated proteins are constituents of the paracrystal. This is the first report of intranuclear paracrystals in cardiomyocytes, which appear to be unique to MLP(-/-) mice.}, number={1}, journal={Microscopy Research and Technique}, author={Muto, M. and Sargeant, A. and Tangkawattana, P. and Takeyasu, K. and Nishijima, Y. and Bonagura, J. and Hoshijima, M. and Nakade, T. and Hosaka, Y. and Faulkner, G. and et al.}, year={2007}, pages={50–54} }
 @article{mechanisms of impaired calcium handling underlying subclinical diastolic dysfunction in diabetes_2007, volume={293}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-36048948863&partnerID=MN8TOARS}, DOI={10.1152/ajpregu.00059.2007}, abstractNote={Isolated diastolic dysfunction is found in almost half of asymptomatic patients with well-controlled diabetes and may precede diastolic heart failure. However, mechanisms that underlie diastolic dysfunction during diabetes are not well understood. We tested the hypothesis that isolated diastolic dysfunction is associated with impaired myocardial Ca(2+) handling during type 1 diabetes. Streptozotocin-induced diabetic rats were compared with age-matched placebo-treated rats. Global left ventricular myocardial performance and systolic function were preserved in diabetic animals. Diabetes-induced diastolic dysfunction was evident on Doppler flow imaging, based on the altered patterns of mitral inflow and pulmonary venous flows. In isolated ventricular myocytes, diabetes resulted in significant prolongation of action potential duration compared with controls, with afterdepolarizations occurring in diabetic myocytes (P < 0.05). Sustained outward K(+) current and peak outward component of the inward rectifier were reduced in diabetic myocytes, while transient outward current was increased. There was no significant change in L-type Ca(2+) current; however, Ca(2+) transient amplitude was reduced and transient decay was prolonged by 38% in diabetic compared with control myocytes (P < 0.05). Sarcoplasmic reticulum Ca(2+) load (estimated by measuring the integral of caffeine-evoked Na(+)-Ca(2+) exchanger current and Ca(2+) transient amplitudes) was reduced by approximately 50% in diabetic myocytes (P < 0.05). In permeabilized myocytes, Ca(2+) spark amplitude and frequency were reduced by 34 and 20%, respectively, in diabetic compared with control myocytes (P < 0.05). Sarco(endo)plasmic reticulum Ca(2+)-ATPase-2a protein levels were decreased during diabetes. These data suggest that in vitro impairment of Ca(2+) reuptake during myocyte relaxation contributes to in vivo diastolic dysfunction, with preserved global systolic function, during diabetes.}, number={5}, journal={American Journal of Physiology - Regulatory Integrative and Comparative Physiology}, year={2007} }
 @article{schwarzwald_schober_bonagura_2007, title={Methods and reliability of echocardiographic assessment of left atrial size and mechanical function in horses}, volume={68}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-34547484335&partnerID=MN8TOARS}, DOI={10.2460/ajvr.68.7.735}, abstractNote={Abstract Objective —To assess the feasibility, describe the techniques, and determine the reliability of transthoracic echocardiography for characterization of left atrial (LA) size and LA mechanical function in horses. Animals —6 healthy adult horses. Procedures —Repeated echocardiographic examinations were performed independently by 2 observers in standing, unsedated horses by use of 2-dimensional echocardiography, pulsed-wave flow Doppler, and tissue Doppler imaging (TDI) techniques. Test reliability was determined by estimating measurement variability, within-day interobserver variability, and between-day inter- and intraobserver variability of all echocardiographic variables. Variability was expressed as the coefficient of variation (CV) and the absolute value below which the difference between 2 measurements will lie with 95% probability. Results —Most echocardiographic variables of LA size had low overall variability (CV, < 15%). Among the 2-dimensional indices of LA mechanical function, area-based and volume-based ejection phase indices had moderate between-day variability (CV usually < 25%). Transmitral Doppler flow indices were characterized by low to high between-day variability (CV, 6% to 35%). The TDI wall motion velocities had high between-day variability (CV, > 25%), whereas most TDI-derived time intervals had low variability (CV, < 15%). Conclusions and Clinical Relevance —LA size and mechanical function can be reliably assessed in standing, unsedated horses by use of 2-dimensional echocardiography, transmitral blood flow velocity profiles, and analyses of LA wall motion by use of TDI. These results may provide useful recommendations for echocardiographic assessment of LA size and function in horses.}, number={7}, journal={American Journal of Veterinary Research}, author={Schwarzwald, C.C. and Schober, K.E. and Bonagura, J.D.}, year={2007}, pages={735–747} }
 @article{miller_gordon_saunders_arsenault_meurs_lehmkuhl_bonagura_fox_2006, title={Angiographic classification of patent ductus arteriosus morphology in the dog}, volume={8}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2006.07.001}, DOI={10.1016/j.jvc.2006.07.001}, abstractNote={To characterize angiographic morphology and minimum internal transverse diameter of left-to-right shunting patent ductus arteriosus (PDA) in a large series of dogs. PDA is the most common congenital cardiac malformation in the dog. Transarterial ductal occlusion is increasingly performed to close this defect. While accurate assessment of ductal morphology and luminal diameter is important to assure optimal occlusion using catheter-delivered devices, such information is currently limited. In 246 dogs representing 31 breeds with left-to-right shunting PDA, right lateral selective aortic angiograms were recorded and reviewed. PDA morphology conformed to four general phenotypes (types I, IIA, IIB, and III) which varied according to degree of ductal tapering, and the presence, absence, or location of abrupt ductal narrowing. Minimum internal ductal diameter for all dogs averaged 2.9 mm (median, 2.5 mm; range, 1.0–9.5 mm) and was not correlated to age or body weight. There was no significant difference in minimum internal diameters between types I, IIA or IIB PDA, whereas, type III PDA was significantly wider (p = 0.024) than other phenotypes. The most frequently-encountered variant (type IIA) was identified in 54.4% of cases (average minimum internal diameter, 2.3 mm [median, 2.2 mm; range, 1.0–5.5 mm]). PDA angiographic morphology was categorized based upon the degree, presence, or absence of ductal narrowing, and the location of ductal attenuation. When planning PDA repair, this information should assist planning, selection and deployment of transcatheter occluding devices.}, number={2}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Miller, Matthew W. and Gordon, Sonya G. and Saunders, Ashley B. and Arsenault, Wendy G. and Meurs, Kathryn M. and Lehmkuhl, Linda B. and Bonagura, John D. and Fox, Philip R.}, year={2006}, month={Nov}, pages={109–114} }
 @article{bonagura_lehmkuhl_2006, title={Cardiomyopathy}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882446413&partnerID=MN8TOARS}, DOI={10.1016/b0-72-160422-6/50152-2}, journal={Saunders Manual of Small Animal Practice}, publisher={Elsevier}, author={Bonagura, John D. and Lehmkuhl, Linda B.}, year={2006}, pages={1527–1548} }
 @article{bonagura_schober_2006, title={Cardiovascular Drugs}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882332846&partnerID=MN8TOARS}, DOI={10.1016/b0-72-160422-6/50148-0}, journal={Saunders Manual of Small Animal Practice}, publisher={Elsevier}, author={Bonagura, John D. and Schober, Karsten E.}, year={2006}, pages={1473–1494} }
 @inbook{bonagura_samii_2006, title={Cardiovascular Radiography}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882414861&partnerID=MN8TOARS}, DOI={10.1016/B0-72-160422-6/50145-5}, booktitle={Saunders Manual of Small Animal Practice}, publisher={Elsevier}, author={Bonagura, John D. and Samii, Valerie F.}, year={2006}, pages={1430–1440} }
 @article{green_bonagura_2006, title={Congenital Heart Disease}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882297987&partnerID=MN8TOARS}, DOI={10.1016/b0-72-160422-6/50156-x}, journal={Saunders Manual of Small Animal Practice}, publisher={Elsevier}, author={Green, Henry W. and Bonagura, John D.}, year={2006}, pages={1589–1598} }
 @article{schwarzwald_stewart_morrison_bonagura_2006, title={Cor pulmonale in a horse with granulomatous pneumonia}, volume={18}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33747767986&partnerID=MN8TOARS}, number={4}, journal={Equine Veterinary Education}, author={Schwarzwald, C.C. and Stewart, A.J. and Morrison, C.D. and Bonagura, J.D.}, year={2006}, pages={182–187} }
 @article{koplitz_meurs_bonagura_2006, title={Echocardiographic Assessment of the Left Ventricular Outflow Tract in the Boxer}, volume={20}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.2006.tb01804.x}, DOI={10.1111/j.1939-1676.2006.tb01804.x}, abstractNote={Background : Soft, variable ejection murmurs are common in Boxers and are associated with increased left ventricular outflow tract (LVOT) ejection velocities. Whether these murmurs are physiologic or indicate mild aortic stenosis is controversial. Ejection velocity is impacted by LVOT area and ventricular stroke volume (SV), suggesting that these variables are pertinent to murmur development. Hypothesis : Boxers with ejection murmurs have a smaller LVOT and equivalent SV indices, compared with values in dogs without murmurs. Animals : Three age‐and weight‐matched groups of dogs—15 Boxers with soft ejection murmurs (group I); 15 Boxers without murmurs (group II); and 15 nonBoxer dogs without murmurs (group III) — were studied. Methods : All dogs underwent 2‐dimensional and Doppler echocardiographic examinations. The LVOT size at multiple levels; LVOT ejection velocity, stroke distance, and SV index; and right ventricular SV index were determined and compared by analysis of variance. Results : Indexed LVOT areas in Boxer groups were not different, but were significantly smaller than those of non‐Boxer dogs. Ejection velocities and stroke distances were significantly different across all groups, with group I having the highest and group III having the lowest values. Doppler SV indices (ml/m 2 ) for group‐I versus group‐II Boxers were 70±16(SD) versus 62±12 for the LVOT ( P = .27) and 58±12 versus 48±9 for the right ventricle ( P = .14). Conclusions and clinical importance : These data suggest that a relatively smaller LVOT in Boxers predisposes them to increased ejection velocity and development of murmurs. The contribution of SV to the genesis of these often labile murmurs requires additional study.}, number={4}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Koplitz, S.L. and Meurs, K.M. and Bonagura, J.D.}, year={2006}, month={Jul}, pages={904–911} }
 @article{koplitz_meurs_bonagura_2006, title={Echocardiographic assessment of the left ventricular outflow tract in the boxer}, volume={20}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33748361334&partnerID=MN8TOARS}, DOI={10.1892/0891-6640(2006)20[904:EAOTLV]2.0.CO;2}, abstractNote={Background: Soft, variable ejection murmurs are common in Boxers and are associated with increased left ventricular outflow tract (LVOT) ejection velocities.Whether these murmurs are physiologic or indicate mild aortic stenosis is controversial.Ejection velocity is impacted by LVOT area and ventricular stroke volume (SV), suggesting that these variables are pertinent to murmur development.Hypothesis: Boxers with ejection murmurs have a smaller LVOT and equivalent SV indices, compared with values in dogs without murmurs.Animals: Three age-and weight-matched groups of dogs-15 Boxers with soft ejection murmurs (group I); 15 Boxers without murmurs (group II); and 15 nonBoxer dogs without murmurs (group III)-were studied.Methods: All dogs underwent 2-dimensional and Doppler echocardiographic examinations.The LVOT size at multiple levels; LVOT ejection velocity, stroke distance, and SV index; and right ventricular SV index were determined and compared by analysis of variance.Results: Indexed LVOT areas in Boxer groups were not different, but were significantly smaller than those of non-Boxer dogs.Ejection velocities and stroke distances were significantly different across all groups, with group I having the highest and group III having the lowest values.Doppler SV indices (ml/m 2 ) for group-I versus group-II Boxers were 70616(SD) versus 62612 for the LVOT (P 5 .27)and 58612 versus 4869 for the right ventricle (P 5 .14).Conclusions and clinical importance: These data suggest that a relatively smaller LVOT in Boxers predisposes them to increased ejection velocity and development of murmurs.The contribution of SV to the genesis of these often labile murmurs requires additional study.}, number={4}, journal={Journal of Veterinary Internal Medicine}, author={Koplitz, S.L. and Meurs, K.M. and Bonagura, J.D.}, year={2006}, pages={904–911} }
 @article{woodman_ingram_bonagura_laughlin_2006, title={Exercise training improves femoral artery blood flow responses to endothelium-dependent dilators in hypercholesterolemic pigs}, volume={290}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33744923669&partnerID=MN8TOARS}, DOI={10.1152/ajpheart.01026.2005}, abstractNote={We tested two hypotheses: 1) that the effects of hypercholesterolemia on endothelial function in femoral arteries exceed those reported in brachial arteries and 2) that exercise (Ex) training enhances endothelium-dependent dilation and improves femoral artery blood flow (FABF) in hypercholesterolemic pigs. Adult male pigs were fed a normal fat (NF) or high-fat/cholesterol (HF) diet for 20 wk. Four weeks after the diet was initiated, pigs were Ex trained or remained sedentary (Sed) for 16 wk, thus yielding four groups: NF-Sed, NF-Ex, HF-Sed, and HF-Ex. Endothelium-dependent vasodilator responses were assessed in vivo by measuring changes in FABF after intra-arterial injections of ADP and bradykinin (BK). Endothelium-dependent and -independent relaxation was assessed in vitro by measuring relaxation responses to BK and sodium nitroprusside (SNP). FABF increased in response to ADP and BK in all groups. FABF responses to ADP and BK were not impaired by HF but were improved by Ex in HF pigs. BK- and SNP-induced relaxation of femoral artery rings was not altered by HF or Ex. To determine whether the mechanism(s) for vasorelaxation of femoral arteries was altered by HF or Ex, BK-induced relaxation was assessed in vitro in the absence or presence of N(G)-nitro-l-arginine methyl ester [l-NAME; to inhibit nitric oxide synthase (NOS)], indomethacin (Indo; to inhibit cyclooxygenase), or l-NAME + Indo. BK-induced relaxation was inhibited by l-NAME and l-NAME + Indo in all groups of femoral arteries. Ex increased the NOS-dependent component of endothelium-dependent relaxation in NF (not HF) arteries. Indo did not inhibit BK-induced relaxation. Collectively, these results indicate that hypercholesterolemia does not alter endothelial function in femoral arteries and that Ex training improves FABF responses to ADP and BK; however, the improvement cannot be attributed to enhanced endothelial function in HF femoral arteries. These data suggest that Ex-induced improvements in FABF in HF arteries are mediated by vascular adaptations in arteries/arterioles downstream from the femoral artery.}, number={6}, journal={American Journal of Physiology - Heart and Circulatory Physiology}, author={Woodman, C.R. and Ingram, D. and Bonagura, J. and Laughlin, M.H.}, year={2006} }
 @inbook{bonagura_lehmkuhl_morais_2006, title={Fluid and diuretic therapy in heart failure}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84880676778&partnerID=MN8TOARS}, DOI={10.1016/B0-72-163949-6/50024-2}, booktitle={Fluid, Electrolyte and Acid-Base Disorders in Small Animal Practice}, author={Bonagura, J.D. and Lehmkuhl, L.B. and Morais, H.A.}, year={2006}, pages={490–518} }
 @article{bonagura_keene_2006, title={Heart Failure in Dogs}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882373398&partnerID=MN8TOARS}, DOI={10.1016/b0-72-160422-6/50149-2}, journal={Saunders Manual of Small Animal Practice}, publisher={Elsevier}, author={Bonagura, John D. and Keene, Bruce}, year={2006}, pages={1495–1507} }
 @inbook{bonagura_2006, title={Pericardial Diseases}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882395239&partnerID=MN8TOARS}, DOI={10.1016/B0-72-160422-6/50153-4}, booktitle={Saunders Manual of Small Animal Practice}, publisher={Elsevier}, author={Bonagura, John D.}, year={2006}, pages={1549–1560} }
 @article{schwarzwald_sams_bonagura_2006, title={Pharmacokinetics of the calcium-channel blocker diltiazem after a single intravenous dose in horses}, volume={29}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33646240068&partnerID=MN8TOARS}, DOI={10.1111/j.1365-2885.2006.00733.x}, abstractNote={The pharmacokinetics of diltiazem were determined in eight healthy horses. Diltiazem HCl, 1 mg/kg i.v., was administered over 5 min. Venous blood samples were collected at regular intervals after administration. Plasma concentrations of diltiazem and desacetyldiltiazem were determined by high-performance liquid chromatography. A second, putative metabolite was detected, but could not be identified due to the lack of an authentic standard. Data were analyzed by nonlinear least-squares regression analysis. The median (minimum-maximum) peak plasma concentration of diltiazem was 727 (539-976) ng/mL. Plasma diltiazem concentration vs. time data were best described by a two-compartment model with first-order drug elimination. The distribution half-life was 12 (6-23) min, the terminal half-life was 93 (73-161) min, the mean residence time was 125 (99-206) min, total plasma clearance was 14.4 (10.4-18.6) mL/kg/min, and the volume of distribution at steady-state was 1.84 (1.46-2.51) L/kg. The normalized ratio of the area under the curve (AUC) of desacetyldiltiazem to the AUC of diltiazem was 0.088 (0.062-0.179). The disposition of diltiazem in horses was characterized by rapid distribution and elimination and a terminal half-life shorter than reported in humans and dogs. Because of the reported low pharmacologic activity, plasma diltiazem metabolite concentrations were not considered clinically important.}, number={3}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Schwarzwald, C.C. and Sams, R.A. and Bonagura, J.D.}, year={2006}, pages={165–171} }
 @article{bonagura_2006, title={Respiratory Infections}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882402400&partnerID=MN8TOARS}, DOI={10.1016/b0-72-160422-6/50165-0}, journal={Saunders Manual of Small Animal Practice}, publisher={Elsevier}, author={Bonagura, John D.}, year={2006}, pages={1684–1695} }
 @article{bonagura_koplitz_2006, title={Syncope}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882346380&partnerID=MN8TOARS}, DOI={10.1016/b0-72-160422-6/50150-9}, journal={Saunders Manual of Small Animal Practice}, publisher={Elsevier}, author={Bonagura, John D. and Koplitz, Shianne L.}, year={2006}, pages={1508–1512} }
 @article{rush_bonagura_2006, title={Valvular Heart Disease}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84871593709&partnerID=MN8TOARS}, DOI={10.1016/b0-72-160422-6/50151-0}, journal={Saunders Manual of Small Animal Practice}, publisher={Elsevier}, author={Rush, John E. and Bonagura, John D.}, year={2006}, pages={1513–1526} }
 @article{bonagura_stepien_2006, title={Vascular Diseases}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882418966&partnerID=MN8TOARS}, DOI={10.1016/b0-72-160422-6/50155-8}, journal={Saunders Manual of Small Animal Practice}, publisher={Elsevier}, author={Bonagura, John D. and Stepien, Rebecca L.}, year={2006}, pages={1574–1588} }
 @article{nishijima_feldman_bonagura_ozkanlar_jenkins_lacombe_abraham_hamlin_carnes_2005, title={Canine nonischemic left ventricular dysfunction: A model of chronic human cardiomyopathy}, volume={11}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-26844474921&partnerID=MN8TOARS}, DOI={10.1016/j.cardfail.2005.05.006}, abstractNote={Background The mechanisms of cardiac remodeling during chronic heart failure remain poorly defined. We sought to advance a chronic canine model of nonischemic cardiomyopathy. Methods and Results Male dogs (n = 6) received decremental right ventricular apical tachypacing (12 months) to achieve and maintain stable left ventricular (LV) dysfunction. After 10 months of tachypacing, 120 beats/min was sufficient to maintain stable LV dysfunction. Electrocardiography, echocardiography, and tissue Doppler imaging were done to evaluate electrophysiology, LV dimensions and function, and dyssynchrony during normal sinus rhythm. The 6-minute walk test was used to evaluate functional capacity. We observed increases in both QRS duration (P < .0001) and QRS amplitude (P < .0001). LV fractional shortening was reduced from a baseline of 38.0 ± 1.4% to 11.2 ± 1.4% (P < .0001). LV end-diastolic dimension increased from 3.8 ± 0.1 cm at baseline to 5.3 ± 0.3 cm (P < .0001); LV end-systolic dimension increased from 2.3 ± 0.1 cm to 4.7 ± 0.2 cm (P < .0001). LV mass increased from 85.9 ± 3.5 g at baseline to 179 ± 13.7 g (P < .0001). There was evidence of LV dyssynchrony (P < .04) during both normal sinus rhythm and right ventricular tachypacing, compared with control dogs. The distance a dog walked in 6 minutes was significantly less at 12 months compared with normal controls (540 ± 32 m versus 277 ± 64 m, P < .008). Conclusion This nonischemic model of canine cardiomyopathy reproduces many aspects of chronic human heart failure including reduced fractional shortening, dilated ventricular dimensions, increased LV mass, decreased functional capacity, and dyssynchrony.}, number={8}, journal={Journal of Cardiac Failure}, author={Nishijima, Y. and Feldman, D.S. and Bonagura, J.D. and Ozkanlar, Y. and Jenkins, P.J. and Lacombe, V.A. and Abraham, W.T. and Hamlin, R.L. and Carnes, C.A.}, year={2005}, pages={638–644} }
 @article{baumwart_meurs_atkins_bonagura_defrancesco_keene_koplitz_fuentes_miller_rausch_et al._2005, title={Clinical, echocardiographic, and electrocardiographic abnormalities in Boxers with cardiomyopathy and left ventricular systolic dysfunction: 48 cases (1985-2003)}, volume={226}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2005.226.1102}, DOI={10.2460/javma.2005.226.1102}, abstractNote={To identify clinical, echocardiographic, and electrocardiographic abnormalities in Boxers with cardiomyopathy and echocardiographic evidence of left ventricular systolic dysfunction.Retrospective study.48 mature Boxers.Medical records were reviewed for information on age; sex; physical examination findings; and results of electrocardiography, 24-hour ambulatory electrocardiography, thoracic radiography, and echocardiography.Mean age of the dogs was 6 years (range, 1 to 11 years). Twenty (42%) dogs had a systolic murmur, and 9 (19%) had ascites. Congestive heart failure was diagnosed in 24 (50%) dogs. Seventeen (35%) dogs had a history of syncope. Mean fractional shortening was 14.4% (range, 1% to 23%). Mean left ventricular systolic and diastolic diameters were 4.5 cm (range, 3 to 6.3 cm) and 5.3 cm (range, 3.9 to 7.4 cm), respectively. Twenty-eight (58%) dogs had a sinus rhythm with ventricular premature complexes (VPCs), and 20 had supraventricular arrhythmias (15 with atrial fibrillation and 5 with sinus rhythm and atrial premature complexes). Sixteen of the dogs with supraventricular arrhythmias also had occasional VPCs. Morphology of the VPCs seen on lead II ECGs was consistent with left bundle branch block in 25 dogs, right bundle branch block in 8, and both in 11.Results suggest that Boxers with cardiomyopathy and left ventricular dysfunction frequently have arrhythmias of supraventricular or ventricular origin. Whether ventricular dysfunction was preceded by electrical disturbances could not be determined from these data, and the natural history of myocardial disease in Boxers requires further study.}, number={7}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Baumwart, Ryan D. and Meurs, Kathryn M. and Atkins, Clarke E. and Bonagura, John D. and DeFrancesco, Teresa C. and Keene, Bruce W. and Koplitz, Shianne and Fuentes, Virginia Luis and Miller, Matthew W. and Rausch, William and et al.}, year={2005}, month={Apr}, pages={1102–1104} }
 @article{schwarzwald_bonagura_luis-fuentes_2005, title={Effects of diltiazem on hemodynamic variables and ventricular function in healthy horses}, volume={19}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-26844538503&partnerID=MN8TOARS}, DOI={10.1892/0891-6640(2005)19[703:EODOHV]2.0.CO;2}, abstractNote={Quinidine is effective for treatment of atrial fibrillation (AF) in horses, but often accelerates ventricular response rate. Diltiazem effectively controls heart rate response to AF in other species. This investigation determined the effects of diltiazem on cardiac rate and rhythm, left ventricular (LV) function, central hemodynamics, and peripheral blood flow in normal, standing, nonsedated horses. A dose-finding study was performed. Afterward, 8 healthy horses were treated with diltiazem IV every 30 minutes to achieve cumulative dosages of 0 (saline control), 1, 1.5, and 2 mg/kg. Plasma diltiazem concentration, heart rate and rhythm (by electrocardiography), LV function and central hemodynamics (by cardiac catheterization), LV dimensions (by echocardiography), and forelimb blood flow (by Doppler sonography) were determined during each treatment period. Diltiazem plasma concentrations between 390 and 910 ng/mL were achieved, with considerable variation among horses. Cardiac effects of diltiazem included intermittent depression of the sinus and atrioventricular (AV) nodes and mild impairment of systolic and diastolic LV function. Vascular effects of diltiazem included arterial vasodilatation, increased limb blood flow, and decreased systemic vascular resistance. Baroreceptor reflex-mediated sympathetic activation increased sinus node rate and presumably blunted the depressive effects of diltiazem on myocardial and nodal tissues. Two horses developed transient highgrade sinus arrest with severe systemic hypotension. Diltiazem appears relatively safe in healthy horses, but dosage may be limited by hypotension from vasodilatation and direct suppression of sinus node discharge. Because of its inhibitory effects on AV nodal conduction, diltiazem may prove useful for heart rate control in horses with AF.}, number={5}, journal={Journal of Veterinary Internal Medicine}, author={Schwarzwald, C.C. and Bonagura, J.D. and Luis-Fuentes, V.}, year={2005}, pages={703–711} }
 @article{meurs_lehmkuhl_bonagura_2005, title={Survival times in dogs with severe subvalvular aortic stenosis treated with balloon valvuloplasty or atenolol}, volume={227}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2005.227.420}, DOI={10.2460/javma.2005.227.420}, abstractNote={Abstract Objective —To determine survival times in dogs with severe subvalvular aortic stenosis (SAS) treated by means of balloon valvuloplasty or with atenolol, a β-adrenoceptor blocking drug. Design —Prospective study. Animals —38 dogs < 24 months old with severe SAS (peak systolic pressure gradient ≥ 80 mm Hg). Procedure —10 dogs underwent balloon valvuloplasty and were reexamined 6 weeks later to determine the feasibility of the procedure. The remaining 28 dogs were randomly assigned to undergo balloon valvuloplasty (n = 15) or to be treated with atenolol long term (13) and were reexamined annually for 9 years or until the time of death. Results —For the first 10 dogs, mean pressure gradient 6 weeks after balloon valvuloplasty (mean ± SD, 119 ± 32.6 mm Hg) was significantly decreased, compared with mean baseline pressure gradient (167 ± 40.1 mm Hg). Median survival time for dogs that underwent balloon valvuloplasty (55 months) was not significantly different from median survival time for dogs treated with atenolol (56 months). Conclusions and Clinical Relevance —Results suggest that balloon valvuloplasty can result in a significant decrease in the peak systolic pressure gradient in dogs with severe SAS, at least for the short term. No clear benefit in survival times was seen for dogs that underwent balloon valvuloplasty versus dogs that were treated with atenolol. ( J Am Vet Med Assoc 2005;227:420–424)}, number={3}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Meurs, Kathryn M. and Lehmkuhl, Linda B. and Bonagura, John D.}, year={2005}, month={Aug}, pages={420–424} }
 @article{demadron_bonagura_herring_2005, title={TWO-DIMENSIONAL ECHOCARDIOGRAPHY IN THE NORMAL CAT}, volume={26}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84995139744&partnerID=MN8TOARS}, DOI={10.1111/j.1740-8261.1985.tb01401.x}, abstractNote={Two‐dimensional echocardiography (2DE) and M‐mode echocardiography were used to image the heart of 13 clinically healthy cats. Seven awake cats and six cats tranquilized with a combination of acetylpromazine and ketamine were studied. Six cats were studied by 2DE on 3 consecutive days to assess repeatability of the study. Long‐axis and short‐axis echocardiographic tomograms were obtained from the right parasternal location, and these images were used to determine internal cardiac dimensions, ventricular and septal wall thicknesses, repeatability of the study, and interobserver variability. Some but not all parameters were significantly (P < 0.05) related to body weight. Significant correlations (P <0.05) were found between measurements obtained by long‐axis and by short‐axis image planes. Comparison of parameters measured by 2DE and M‐mode echocardiography demonstrated minimal differences between mean values. Repeatability of the 2DE study was good with 14 of 16 parameters having a mean percent error less than 10%. Interobserver variability was acceptable for some but not all parameters. The study indicates that repeatable 2DE tomograms can be obtained in the cat and that quantitation of cardiac anatomy is possible with this imaging technique.}, number={5}, journal={Veterinary Radiology}, publisher={Wiley}, author={DeMadron, Eric and Bonagura, John D. and Herring, David S.}, year={2005}, month={May}, pages={149–158} }
 @article{baumwart_meurs_bonagura_2005, title={Tei Index of Myocardial Performance Applied to the Right Ventricle in Normal Dogs}, volume={19}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.2005.tb02772.x}, DOI={10.1111/j.1939-1676.2005.tb02772.x}, abstractNote={Right ventricular (RV) dysfunction is a cause of exercise intolerance, hypotension, syncope, and heart failure in dogs with cardiac and respiratory disorders. The study objective was to determine Doppler-derived reference values that reflect global RV function in healthy dogs. We measured systolic time intervals and an RV index of myocardial performance (IMP) in 45 healthy dogs between 8 months and 8 years of age. Pulsed-wave Doppler recordings of mitral, tricuspid, aortic, and pulmonic were acquired. Pre-ejection period (PEP), ejection time (ET), PEP/ET, and IMP were determined for both ventricles by separate cardiac cycles. Compared to the mean left ventricular (LV) IMP (0.410; 95% confidence intervals [CI] 0.378–0.442), mean RV IMP (0.250; 95% CI 0.222–0.278) was significantly smaller, and mean ET for the RV (187 millisecond [ms]; 95% CI 182–192) was significantly longer than the LV (173 ms; 95% CI 168–179). A clinically relevant correlation was not found among RV IMP and body weight, heart rate, RV ET, RV PEP, or RV PEP/ET. Calculation of LV IMP with 2 separate sample volumes yielded smaller values than from a single sample volume, with a difference in means of 0.040. We conclude that the RV IMP is relatively independent of body weight and heart rate within the ranges studied and is consistently lower than values derived from the LV in healthy dogs. This study provides additional reference values for RV function in dogs and may be useful for identification of RV dysfunction in dogs.}, number={6}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Baumwart, Ryan D. and Meurs, Kathryn M. and Bonagura, John D.}, year={2005}, month={Nov}, pages={828–832} }
 @article{baumwart_meurs_bonagura_2005, title={Tei index of myocardial performance applied to the right ventricle in normal dogs}, volume={19}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-28444483922&partnerID=MN8TOARS}, DOI={10.1892/0891-6640(2005)19[828:TIOMPA]2.0.CO;2}, abstractNote={Right ventricular (RV) dysfunction is a cause of exercise intolerance, hypotension, syncope, and heart failure in dogs with cardiac and respiratory disorders. The study objective was to determine Doppler-derived reference values that reflect global RV function in healthy dogs. We measured systolic time intervals and an RV index of myocardial performance (IMP) in 45 healthy dogs between 8 months and 8 years of age. Pulsed-wave Doppler recordings of mitral, tricuspid, aortic, and pulmonic were acquired. Pre-ejection period (PEP), ejection time (ET), PEP/ET, and IMP were determined for both ventricles by separate cardiac cycles. Compared to the mean left ventricular (LV) IMP (0.410; 95% confidence intervals [CI] 0.378-0.442), mean RV IMP (0.250; 95% CI 0.222-0.278) was significantly smaller, and mean ET for the RV (187 millisecond [ms]; 95% CI 182-192) was significantly longer than the LV (173 ms; 95% CI 168-179). A clinically relevant correlation was not found among RV IMP and body weight, heart rate, RV ET, RV PEP, or RV PEP/ET. Calculation of LV IMP with 2 separate sample volumes yielded smaller values than from a single sample volume, with a difference in means of 0.040. We conclude that the RV IMP is relatively independent of body weight and heart rate within the ranges studied and is consistently lower than values derived from the LV in healthy dogs. This study provides additional reference values for RV function in dogs and may be useful for identification of RV dysfunction in dogs.}, number={6}, journal={Journal of Veterinary Internal Medicine}, author={Baumwart, R.D. and Meurs, K.M. and Bonagura, J.D.}, year={2005}, pages={828–832} }
 @article{bonagura_reef_2004, title={Disorders of the Cardiovascular System}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84942588742&partnerID=MN8TOARS}, DOI={10.1016/b0-72-169777-1/50010-x}, journal={Equine Internal Medicine}, publisher={Elsevier}, author={Bonagura, John D. and Reef, Virginia B.}, year={2004}, pages={355–459} }
 @article{kottwitz_preziosi_miller_ramos-vara_maggs_bonagura_2004, title={Heart failure caused by toxoplasmosis in a fennec fox (Fennecus zerda)}, volume={40}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-31844445419&partnerID=MN8TOARS}, DOI={10.5326/0400501}, abstractNote={A male fennec fox (Fennecus zerda) kit was examined for lethargy, inappetence, and weight loss. Clinical findings included respiratory distress, a gallop rhythm, and retinochoroiditis. Radiography indicated pleural effusion and cardiomegaly. Echocardiographic findings included left ventricular dilatation, low left ventricular ejection fraction, and atrioventricular valvular regurgitation. Necropsy findings were compatible with a diagnosis of congestive heart failure caused by myocarditis. Histopathology showed a disseminated infection with Toxoplasma gondii causing myocarditis, skeletal polymyositis, gastrointestinal myositis, and panuveitis. Toxoplasma-induced myocarditis should be included in the differential diagnosis of heart failure and retinochoroiditis in the fennec fox.}, number={6}, journal={Journal of the American Animal Hospital Association}, author={Kottwitz, J.J. and Preziosi, D.E. and Miller, M.A. and Ramos-Vara, J.A. and Maggs, D.J. and Bonagura, J.D.}, year={2004}, pages={501–507} }
 @article{smithenson_mattoon_bonagura_abrahamsen_drost_2004, title={Pulsed-wave doppler ultrasonographic evaluation of hepatic veins during variable hemodynamic states in healty anesthetized dogs}, volume={65}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-3042532458&partnerID=MN8TOARS}, DOI={10.2460/ajvr.2004.65.734}, abstractNote={To quantify direction and velocity of blood flow in hepatic veins in dogs under different hemodynamic conditions by use of pulsed-wave Doppler ultrasonography.10 healthy dogs.Dogs were anesthetized, and venous flow velocities in the quadrate lobe were measured. Arterial blood pressure, right atrial pressure, pulmonary artery pressure, and cardiac output were measured simultaneously. The timing of each waveform during the cardiac cycle was used to identify velocity profiles. Peak waveform velocities were measured during conditions of light anesthesia with isoflurane (baseline; period 1), cardiovascular depression following administration of high-dose isoflurane and esmolol i.v. (period 2), cardiovascular depression with crystalloid volume expansion (period 3), and high cardiac output induced with dobutamine (period 4). Hemodynamic measurements and maximum waveform velocities were compared among the 4 periods by use of an ANOVA and univariate and multivariate linear regression.During each study period, 4 distinct, low-velocity waves were identified. Mean velocities recorded during period 1 were as follows: retrograde atrial contraction a-wave, 7.3 cm/s; antegrade systolic S-wave, 15.0 cm/s; retrograde venous return v-wave, 2.7 cm/s; and antegrade diastolic D-wave, 11.4 cm/s. Mean S:D ratio was 1.27. During periods 3 and 4, S-wave velocity increased; D-wave velocity was highest during period 4.Consistent hepatic venous velocity profiles were observed in healthy dogs under different hemodynamic conditions. These findings provide baseline values that may be useful in evaluating clinical cases, but further study involving healthy, awake dogs and dogs with cardiac and hepatic diseases is required.}, number={6}, journal={American Journal of Veterinary Research}, author={Smithenson, B.T. and Mattoon, J.S. and Bonagura, J.D. and Abrahamsen, E.J. and Drost, W.T.}, year={2004}, pages={734–740} }
 @article{koplitz_meurs_spier_bonagura_fuentes_wright_2003, title={Aortic ejection velocity in healthy Boxers with soft cardiac murmurs and Boxers without cardiac murmurs: 201 cases (1997–2001)}, volume={222}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2003.222.770}, DOI={10.2460/javma.2003.222.770}, abstractNote={Abstract Objective —To determine aortic ejection velocity in healthy adult Boxers with soft ejection murmurs without overt structural evidence of left ventricular outflow tract obstruction and in healthy Boxers without cardiac murmurs. Design —Retrospective study. Animals —201 Boxers. Procedure —Dogs were examined independently by 2 individuals for evidence of a cardiac murmur, and a murmur grade was assigned. Maximal instantaneous (peak) aortic ejection velocity was measured by means of continuous-wave Doppler echocardiography from a subcostal location. Forty-eight dogs were reexamined approximately 1 year later. Results —A soft (grade 1, 2, or 3) left-basilar ejection murmur was detected in 113 (56%) dogs. Overall median aortic ejection velocity was 1.91 m/s (range, 1.31 to 4.02 m/s). Dogs with murmurs had significantly higher aortic ejection velocities than did those without murmurs (median, 2.11 and 1.72 m/s, respectively). Auscultation of a murmur was 87% sensitive and 66% specific for the identification of aortic ejection velocity > 2.0 m/s. An ejection murmur and aortic ejection velocity > 2.0 m/s were identified in 73 (36%) dogs. For most dogs, observed changes in murmur grade and aortic ejection velocity during a follow-up examination 1 year later were not clinically important. Conclusions and Clinical Relevance —Results suggested that ejection murmurs were common among healthy adult Boxers and that Boxers with murmurs were likely to have high (> 2.0 m/s) aortic ejection velocities. The cause of the murmurs in these dogs is unknown. ( J Am Vet Med Assoc 2003;222:770–774)}, number={6}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Koplitz, Shianne L. and Meurs, Kathryn M. and Spier, Alan W. and Bonagura, John D. and Fuentes, Virginia Luis and Wright, Nicola A.}, year={2003}, month={Mar}, pages={770–774} }
 @article{nout_hinchcliff_bonagura_meurs_papenfuss_2003, title={Cardiac Amyloidosis in a Horse}, volume={17}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0041883774&partnerID=MN8TOARS}, DOI={10.1892/0891-6640(2003)017<0588:CAIAH>2.3.CO;2}, abstractNote={Journal of Veterinary Internal MedicineVolume 17, Issue 4 p. 588-592 Open Access Cardiac Amyloidosis in a Horse Yvette S. Nout, Yvette S. Nout Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH DVM, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 601 Vernon L Tharp Street, Columbus, OH 43210-4007; E-mail: [email protected]Search for more papers by this authorKenneth W. Hinchcliff, Kenneth W. Hinchcliff Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OHSearch for more papers by this authorJohn D. Bonagura, John D. Bonagura Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OHSearch for more papers by this authorKathryn M. Meurs, Kathryn M. Meurs Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OHSearch for more papers by this authorTracey L. Papenfuss, Tracey L. Papenfuss Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OHSearch for more papers by this author Yvette S. Nout, Yvette S. Nout Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH DVM, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 601 Vernon L Tharp Street, Columbus, OH 43210-4007; E-mail: [email protected]Search for more papers by this authorKenneth W. Hinchcliff, Kenneth W. Hinchcliff Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OHSearch for more papers by this authorJohn D. Bonagura, John D. Bonagura Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OHSearch for more papers by this authorKathryn M. Meurs, Kathryn M. Meurs Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OHSearch for more papers by this authorTracey L. Papenfuss, Tracey L. Papenfuss Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OHSearch for more papers by this author First published: 28 June 2008 https://doi.org/10.1111/j.1939-1676.2003.tb02484.xCitations: 9 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1 Marr CM. Cardiology of the Horse. London : WB Saunders; 1999: 10, 102, 298– 311. 2 Davis JL, Gardner SY, Schwabenton B., Breuhaus BA. Congestive heart failure in horses: 14 cases (1984–2001). J Am Vet Med Assoc 2002; 220: 1512– 1515. 3 Hoffman A., Levi O., Orgad U., Nyska A. 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Equine Vet J Suppl 1990; 10: 8– 11. 25 Hayden DW, Johnson KH, Wolf CB, Westermark P. AA amyloid-associated gastroenteropathy in a horse. J Comp Pathol 1988; 98: 195– 204. 26 Hawthorne TB, Bolon B., Meyer DJ. Systemic amyloidosis in a mare. J Am Vet Med Assoc 1990; 196: 323– 325. 27 Glenner GG. Amyloid deposits and amyloidosis. The beta-fi-brilloses (first of two parts). N Engl J Med 1980; 302: 1283– 1292. 28 Khan MF, Falk RH. Amyloidosis. Postgrad Med J 2001; 77: 686– 693. 29 Buxbaum JN, Genega EM, Lazowski P., et al. Infiltrative non-amyloidotic monoclonal immunoglobulin light chain cardiomyopathy: An underappreciated manifestation of plasma cell dyscrasias. Cardiology 2000; 93: 220– 228. 30 Braunwald E. Heart disease: A textbook of cardiovascular medicine, 4th ed. Philadelphia , PA : WB Saunders; 1992: 1416– 1419. 31 Willerson JT, Cohn JN. Cardiovascular medicine, 2nd ed. Philadelphia , PA : Harcourt; 2000: 1082– 1086. Citing Literature Volume17, Issue4July 2003Pages 588-592 ReferencesRelatedInformation}, number={4}, journal={Journal of Veterinary Internal Medicine}, author={Nout, Y.S. and Hinchcliff, K.W. and Bonagura, J.D. and Meurs, K.M. and Papenfuss, T.L.}, year={2003}, pages={588–592} }
 @article{schober_luis fuentes_bonagura_2003, title={Comparison between invasive hemodynamic measurements and noninvasive assessment of left ventricular diastolic function by use of Doppler echocardiography in healthy anesthetized cats}, volume={64}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0037247071&partnerID=MN8TOARS}, DOI={10.2460/ajvr.2003.64.93}, abstractNote={Abstract Objective —To compare Doppler echocardiographic variables of left ventricular (LV) function with those obtained invasively via cardiac catheterization under a range of hemodynamic conditions. Animals —7 healthy anesthetized cats (1 to 3 years of age). Procedure —Cats were anesthetized and instrumented to measure the time constant of isovolumic relaxation (tau [ ]), LV end-diastolic pressure (LVEDP), peak negative and positive rate of change of LV pressure, arterial blood pressure, and cardiac output. Echocardiographic variables of diastolic function (isovolumic relaxation time [IVRT], early LV flow propagation velocity [Vp], transmitral and pulmonary venous flow velocity indices, and LV tissue Doppler imaging indices) were measured simultaneously over a range of hemodynamic states induced by treatments with esmolol, dobutamine, cilobradine, and volume loading. Correlation between invasive and noninvasive measures of LV filling was determined by univariate and multivariate regression analyses. Results —Significant correlations were found between and IVRT, peak Vp, peak late transmitral flow velocity, and peak systolic pulmonary venous flow velocity. A significant correlation was found between LVEDP and early diastolic transmitral flow velocity (peak E) and the ratio of peak E to peak Vp, but not between LVEDP and peak Vp. Conclusion and Clinical Relevance —IVRT and Vp can be used as noninvasive indices of LV relaxation; Vp was independent of preload and heart rate in this study. The E:Vp ratio may be useful as an indicator of LV filling pressure. ( Am J Vet Res 2003;64:93–103)}, number={1}, journal={American Journal of Veterinary Research}, author={Schober, K.E. and Luis Fuentes, V. and Bonagura, J.D.}, year={2003}, pages={93–103} }
 @inbook{bonagura_2003, title={Congenital Heart Disease}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33845234764&partnerID=MN8TOARS}, DOI={10.1016/B978-0-7216-9540-2.50172-9}, booktitle={Current Therapy in Equine Medicine: Fifth Edition}, author={Bonagura, J.D.}, year={2003}, pages={591–601} }
 @article{palacio_luis fuentes_bonagura_schober_hatfield_laughlin_2003, title={Evaluation of transcutaneous Doppler ultrasonography for the measurement of blood flow in the femoral artery of pigs}, volume={64}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0037250749&partnerID=MN8TOARS}, DOI={10.2460/ajvr.2003.64.43}, abstractNote={Abstract Objective —To compare measurements of blood flow in the common femoral artery obtained by duplex Doppler ultrasonography (DDU) and a reference ultrasonic transit-time flow (TTF) method and to examine the impact of Doppler spectral waveform measurement techniques on volumetric estimates. Animals —5 healthy female pigs. Procedure —Femoral arterial blood flow was measured simultaneously in anesthetized pigs by use of a TTF probe (left femoral artery) and transcutaneous DDU (right femoral artery). A range of flow states was induced pharmacologically by using xylazine, bradykinin, dobutamine, and isoflurane. Volumetric blood flow was calculated from DDU waveforms, using the product of the flow velocity integral (FVI), the cross-sectional vessel area, and heart rate. Three calculations of FVI were obtained by manually tracing the Doppler spectral envelopes at the outer envelope, the modal, and the inner envelope of the spectral dispersion pattern. Data analysis included calculation of Pearson correlation coefficients and Bland-Altman limits of agreement. Results —Blood flow measured by DDU was more closely correlated with TTF measurements when the modal or inner envelope tracing method was used ( r , 0.76 and 0.78; limits of agreement, –100 to 54.2 and –48.5 to 77.0 mL/min, respectively). Limits of agreement for the outer envelope tracing method were –238.5 to 64 mL/min. Conclusion and Clinical Relevance —Transcutaneous DDU is a reliable noninvasive technique for measuring blood flow in the femoral artery of pigs over a range of flow states. Tracing the inner envelope of the Doppler spectral dispersion pattern provided the best estimate of blood flow in this study. ( Am J Vet Res 2003;64:43–50)}, number={1}, journal={American Journal of Veterinary Research}, author={Palacio, M.J. and Luis Fuentes, V. and Bonagura, J.D. and Schober, K.E. and Hatfield, D.G. and Laughlin, M.H.}, year={2003}, pages={43–50} }
 @article{biodegradable microparticles for in vivo glomerular targeting: implications for gene therapy of glomerular disease_2002, volume={4}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0036313056&partnerID=MN8TOARS}, DOI={10.1023/A:1016044313036}, number={3}, journal={Biomedical Microdevices}, year={2002}, pages={189–195} }
 @article{mcdaniel_magin_madsen_bonagura_schuder_curtis_2002, title={Transthoracic defibrillation of dogs with Edmark, biphasic, and quadriphasic waveforms}, volume={35}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0036154113&partnerID=MN8TOARS}, DOI={10.1054/jelc.2002.30701}, abstractNote={Patients with high transthoracic impedance are reported to be at higher risk of poor outcomes when treated by present defibrillators. This study evaluates the defibrillation efficacy of biphasic truncated exponential (BTE), quadriphasic truncated exponential (QTE), and Edmark waveforms at simulated low, average, and high impedance levels. Waveforms were tested at 2 energy levels in random order in anesthetized dogs (n = 15, 16.9 +/- 1.2 kg), and a supplemental study estimated the ED50 peak current for BTE and QTE at a simulated high impedance level. Overall, BTE and QTE were equivalent, and both were superior to Edmark at equal delivered energies (P<.0001). However, in simulated high impedance patients at 24 J, QTE was superior to BTE (71% vs. 49%, P =.011 (borderline significance-see text)). Supplemental study, QTE mean ED50 peak current was lower than BTE (7.9 vs. 8.9 A, P =.0049). QTE and BTE waveforms were superior to Edmark at all studied conditions, but QTE appears to be superior to BTE in simulated high impedance patients.}, number={1}, journal={Journal of Electrocardiology}, author={McDaniel, W.C. and Magin, T. and Madsen, R.W. and Bonagura, J.D. and Schuder, J.C. and Curtis, J.J.}, year={2002}, pages={45–52} }
 @article{bonagura_2001, title={Problems in the Canine Left Ventricular Outflow Tract}, volume={15}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0035462861&partnerID=MN8TOARS}, DOI={10.1111/j.1939-1676.2001.tb01570.x}, abstractNote={Journal of Veterinary Internal MedicineVolume 15, Issue 5 p. 427-429 Open Access Problems in the Canine Left Ventricular Outflow Tract John D. Bonagura DVM, DACVIM, John D. Bonagura DVM, DACVIM Department of Veterinary Clinical Sciences College of Veterinary Medicine Ohio State University Columbus, OH 43210 e-mail: [email protected]Search for more papers by this author John D. Bonagura DVM, DACVIM, John D. Bonagura DVM, DACVIM Department of Veterinary Clinical Sciences College of Veterinary Medicine Ohio State University Columbus, OH 43210 e-mail: [email protected]Search for more papers by this author First published: 28 June 2008 https://doi.org/10.1111/j.1939-1676.2001.tb01570.xCitations: 9AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. References 1 Buchanan JW. Prevalence of cardiovascular disorders. In: PR Fox, DD Sisson, NS Moise, eds. Textbook of Canine and Feline Cardiology. Philadelphia , PA : WB Saunders; 1999: 457– 470. 2 Kienle RD, Thomas WP, Pion PD. The natural clinical history of canine congenital subaortic stenosis. J Vet Intern Med 1994; 8: 423– 431. 3 Pyle RL, Patterson DF, Chacko S. The genetics and pathology of discrete subaortic stenosis in the Newfoundland dog. Am Heart J 1976; 92: 324– 334. 4 Bussadori C, Amberger C, Le Bobinnec G, Lombard CW. Guidelines for the echocardiographic studies of suspected subaortic and pul-monic stenosis. J Vet Cardiol 2000; 2: 17. 5 Sisson DD, Thomas WP, Bonagura JD. Congenital heart disease. In: SJ Ettinger, EC Feldman, eds. Textbook of Veterinary Internal Medicine, 5th ed. Philadelphia , PA : WB Saunders; 2000: 737– 787. 6 Lehmkuhl LB, Bonagura JD. Comparison of catheterization and Doppler-derived pressure gradients in a canine model of subaortic stenosis. J Am Soc Echocardiogr 1995; 8: 611– 620. 7 Weyman AE, Griffin BP Left ventricular outflow tract: The aortic valve, aorta, and subvalvular outflow tract. In: AE Weyman, ed. Principles and Practice of Echocardiography, 2nd ed. Philadelphia , PA : Lea & Febiger; 1994: 498– 574. 8 Bélanger MC, DiFruscia R, Dumesnil JG, Pibarot P. Usefulness of the indexed effective orifice area in the assessment of subaortic stenosis in the dog. J Vet Intern Med 2001; 15: 430– 437. 9 Orton EC, Herndon GD, Boon JA, et al. Influence of open surgical correction on intermediate-term outcome in dogs with subvalvular aortic stenosis: 44 cases (1991–1998). J Am Vet Med Assoc 2000; 216: 364– 367. 10 Lehmkuhl LB, Bonagura JD. Comparison of transducer placement sites for Doppler echocardiography in dogs with subaortic stenosis. Am J Vet Res 1994; 55: 192– 198. 11 Brown DJ, Knight DH, King RR. Use of pulsed-wave Doppler echocardiography to determine aortic and pulmonary velocity and flow variables in clinically normal dogs. Am J Vet Res 1991; 52: 543– 550. Citing Literature Volume15, Issue5September 2001Pages 427-429 ReferencesRelatedInformation}, number={5}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Bonagura, John D.}, year={2001}, month={Sep}, pages={427–429} }
 @article{moneva-jordan_corcoran_french_dukes-mcewan_martin_luis fuentes_hitchcock_bonagura_2001, title={Sick sinus syndrome in nine West Highland white terriers}, volume={148}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0035798878&partnerID=MN8TOARS}, DOI={10.1136/vr.148.5.142}, abstractNote={Sick sinus syndrome is a clinical term used to describe the clinical signs of sinus node dysfundion. This paper describes the clinical data from nine West Highland white terriers, eight females and one male, in which a diagnosis of sick sinus syndrome was made. The most common clinical signs were episodic weakness and presyncope. Electrocardiographic findings included sinus bradycardia, sinus arrest with or without escape complexes, disturbances of atrioventricular conduction, paroxysmal supraventricular tachycardia, or some combination of these dysrhythmias. The main radiographic changes were mild right‐sided cardiomegaly in five cases, and a slight increase in bronchial and interstitial markings in four, but there was no evidence of congestive heart failure in any of the dogs. Echocardiography revealed mild to moderate mitral endocardiosis in three cases with no other significant abnormalities. The dogs' responses to parenteral atropine were variable and were not necessarily related to their response to oral anticholinergic agents. Five of the dogs were initially treated with propantheline bromide, but in only two of them were the clinical signs controlled in the long term. Six of the dogs were successfully treated by the implantation of a transvenous pacemaker.}, number={5}, journal={Veterinary Record}, author={Moneva-Jordan, A. and Corcoran, B.M. and French, A. and Dukes-Mcewan, J. and Martin, M.W.S. and Luis Fuentes, V. and Hitchcock, L.S. and Bonagura, J.D.}, year={2001}, pages={142–147} }
 @article{bonagura_2000, title={PHYSICAL EXAMINATION}, DOI={10.1016/b978-1-56053-352-8.50022-5}, journal={Small Animal Cardiology Secrets}, publisher={Elsevier}, author={Bonagura, John D.}, year={2000}, pages={97–105} }
 @article{suedmeyer_hitchcock_bonagura_kreeger_smith_2000, title={Ventricular septal defect in a blue duiker (Cephalophus monticola)}, volume={31}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034278581&partnerID=MN8TOARS}, DOI={10.1638/1042-7260(2000)031[0408:VSDIAB]2.0.CO;2}, abstractNote={A 9-mo-old female blue duiker (Cephalophus monticola) weighing 3.9 kg was diagnosed with a cardiac murmur during quarantine examination. Evaluation of the heart by auscultation, electrocardiography, two-dimensional echocardiography, and Doppler color-flow echocardiography revealed a restrictive outlet ventricular septal defect with left atrial and left ventricular dilation. Trivial mitral, tricuspid, and aortic regurgitation was also noted. Though the duiker was clinically asymptomatic at the time of cardiac evaluation, it was found dead 1 wk later. The cause of death was not determined.}, number={3}, journal={Journal of Zoo and Wildlife Medicine}, author={Suedmeyer, Wm.K. and Hitchcock, L.S. and Bonagura, J.D. and Kreeger, J. and Smith, T.}, year={2000}, pages={408–411} }
 @article{shiry_medeiros_mccune_bonagura_1999, title={Heart Murmurs, Valvular Regurgitation and Electrical Disturbances in Copper-Deficient Genetically Hypertensive, Hypertrophic Cardiomyopathic Rats}, volume={18}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0033059639&partnerID=MN8TOARS}, DOI={10.1080/07315724.1999.10718827}, abstractNote={Objective: Rats with a genetic tendency to develop hypertensive, hypertrophic cardiomyopathy were fed copper-deficient diets and their cardiac responses were investigated.Methods: Five male weanling rats of the Long-Evans and SHHF/Mcc-facp strains were randomly selected to receive diets containing either adequate quantities of copper (94.5 μmol Cu/kg diet) or reduced quantities of copper (<15.8 μmol Cu/kg diet) for 6 weeks, (n=5 within each group). Echocardiograms and electrocardiograms were recorded and analyzed at the end of the 6-week interval.Results: Electrocardiograms from copper deficient groups showed longer Q-T intervals and increased QRS amplitudes than controls. Both the copper deficient and control SHHF groups demonstrated significant QRS complex prolongation compared to Long-Evans rats. Echocardiography analysis showed significant increases in left ventricular area, free wall dimension, and myocardial cross-sectional areas in rats fed a copper deficient diet. The frequency of systolic cardiac murmurs increased in copper deficient rats and were related to the presence of valvular regurgitation as determined from echocardiography.Discussion: However, the data do not suggest that a copper-deficient diet fed to a strain of rats genetically susceptible to heart disease later in life, hastens or worsens the onset of cardiac disease. The genetic predisposition and copper-deficient states exert independent effects upon the heart.}, number={1}, journal={Journal of the American College of Nutrition}, author={Shiry, L.J. and Medeiros, D.M. and McCune, S.A. and Bonagura, J.D.}, year={1999}, pages={51–60} }
 @article{miller_lehmkuhl_bonagura_beall_1999, title={Retrospective analysis of the clinical utility of ambulatory electrocardiographic (Holter) recordings in syncopal dogs: 44 cases (1991-1995).}, volume={13}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0033087802&partnerID=MN8TOARS}, DOI={10.1111/j.1939-1676.1999.tb01138.x}, abstractNote={The objective of this study was to evaluate retrospectively the clinical utility of ambulatory (Holter) electrocardiographic monitoring in syncopal dogs and to compare the Holter recording with the clinic electrocardiogram (ECG) in these animals. Fifty Holter reports and 44 medical records from 44 dogs were evaluated. A syncopcal episode occurred during monitoring in 24% of the recordings. No obvious relationship was found between the frequency of syncope occurring before Holter recording and the likelihood of a dog having an episode during recording. Holter recordings were helpful in establishing a diagnosis 42% of the time, but no relationship was detected between the frequency of episodes occurring before Holter recording and the likelihood of a diagnostically useful Holter. An arrhythmia was ruled out as the cause of syncope in 12% of the recordings and was implicated as the cause of syncope in 30% of recordings. Of these, 20% were ventricular tachyarrhythmias and 10% were bradyarrhythmias including pacemaker failure. Ambulatory electrocardiographic recordings led to a therapeutic change in 38% of cases. A comparison of the Holter recordings and clinic ECGs documented the expected increased sensitivity for Holter detection of arrhythmias. The average clinic ECG heart rate consistently exceeded the average Holter heart rate with a mean difference between the average heart rates recorded by the two techniques of 31 bpm (range — 8–87 bpm).}, number={2}, journal={Journal of veterinary internal medicine / American College of Veterinary Internal Medicine}, author={Miller, R.H. and Lehmkuhl, L.B. and Bonagura, J.D. and Beall, M.J.}, year={1999}, pages={111–122} }
 @article{harold laughlin_m. mcallister_jasperse_hitchcock_bonagura_1998, title={Acetylcholine is a vasodilator of porcine skeletal muscle arteries}, volume={120}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0032075780&partnerID=MN8TOARS}, DOI={10.1016/S1095-6433(98)10035-1}, abstractNote={The purpose of this study was to test the hypothesis that porcine skeletal muscle arteries exhibit concentration-dependent vasodilation in response to acetylcholine (ACH) as observed in other mammals. We conducted three experiments. First, vasorelaxation responses to ACH were examined in isolated segments of femoral and brachial arteries, mounted on myographs and studied in vitro. Second, we determined whether resistance arteries from porcine skeletal muscle exhibit vasodilation in response to ACH by isolating second order arterioles (2-A) from the medial (MHT), deep-long (LOH) and lateral (LAT) heads of the triceps brachii muscles of four pigs. The rationale for selection of arterioles from these muscles was that these muscles represent muscles composed primarily of slow-oxidative, fast-oxidative-glycolytic, and fast-glycolytic muscle fiber types, respectively. 2-As were isolated and cannulated with micropipettes and intraluminal pressure set at 60 cm H2O. In both sets of in vitro experiments, we determined responses to an endothelium-independent dilator, sodium nitroprusside (10−10–10−4 M), and to endothelium-dependent agents ACH (10−10–10−4 M), and bradykinin (BK; 10−11–10−6 M). Third, we used transcutaneous ultrasound imaging to measure changes in artery diameters and Doppler-principle measurements of blood flow velocities to estimate changes in total blood flow in the femoral vascular bed. Results reveal that ACH and BK produced similar vasorelaxation responses in femoral and brachial arteries and vasodilation of skeletal muscle 2-As. Also, ACH produced increases in blood flow and decreases in vascular resistance in the femoral vascular bed. These results indicate that the arterial tree of porcine skeletal muscle exhibits ACH-induced, endothelium-dependent vasodilation.}, number={2}, journal={Comparative Biochemistry and Physiology - A Molecular and Integrative Physiology}, author={Harold Laughlin, M. and M. McAllister, R. and Jasperse, J.L. and Hitchcock, L.S. and Bonagura, J.D.}, year={1998}, pages={345–354} }
 @article{bonagura_miller_1998, title={Doppler Echocardiography II}, volume={28}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0032197822&partnerID=MN8TOARS}, DOI={10.1016/s0195-5616(98)50127-1}, abstractNote={Color Doppler imaging (CDI) is a sophisticated form of ultrasound technology that overlays blood flow and velocity information onto a B-mode, two-dimensional, gray-scale image. This imaging technique—also called color Doppler echocardiography, color-coded Doppler, Doppler color-flow imaging, and color-flow imaging—is a type of pulsed-wave Doppler echocardiography. Because the anatomical site of received Doppler-shift information can be readily determined, CDI is useful for documenting normal blood flow patterns and screening the heart and great vessels for areas of abnormal flow.}, number={6}, journal={Veterinary Clinics of North America: Small Animal Practice}, publisher={Elsevier BV}, author={Bonagura, John D. and Miller, Matthew W.}, year={1998}, month={Nov}, pages={1361–1389} }
 @article{bonagura_miller_darke_1998, title={Doppler echocardiography. I. Pulsed-wave and continuous-wave examinations.}, volume={28}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0032197615&partnerID=MN8TOARS}, DOI={10.1016/S0195-5616(98)50126-X}, abstractNote={Doppler echocardiography is a specialized processing of cardiac ultrasound that is characterized by a continuously updated display of blood velocity during the cardiac cycle. Doppler examinations, which include color-coded Doppler echocardiography, pulsed-wave examination, and continuous-wave studies, are readily applicable to veterinary patients.}, number={6}, journal={The Veterinary clinics of North America. Small animal practice}, author={Bonagura, J.D. and Miller, M.W. and Darke, P.G.}, year={1998} }
 @article{bonagura_1997, title={Feline hypertrophic cardiomyopathy}, volume={19}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-1842867146&partnerID=MN8TOARS}, DOI={10.1080/01652176.1997.9694776}, number={sup1}, journal={Veterinary Quarterly}, publisher={Informa UK Limited}, author={Bonagura, J.D.}, year={1997}, month={Apr}, pages={5–6} }
 @article{bonagura_1997, title={Feline restrictive cardiomyopathy}, volume={19}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-1842856152&partnerID=MN8TOARS}, DOI={10.1080/01652176.1997.9694775}, abstractNote={(1997). Feline restrictive cardiomyopathy. Veterinary Quarterly: Vol. 19, No. sup1, pp. 3-4.}, number={sup1}, journal={Veterinary Quarterly}, publisher={Informa UK Limited}, author={Bonagura, J.D.}, year={1997}, month={Apr}, pages={3–4} }
 @article{bonagura_1997, title={Management of congestive heart failure in dogs}, volume={19}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-1842834300&partnerID=MN8TOARS}, DOI={10.1080/01652176.1997.9694774}, abstractNote={"Management of congestive heart failure in dogs." Veterinary Quarterly, 19(sup1), pp. 2–3 Notes Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, USA.}, number={sup1}, journal={Veterinary Quarterly}, publisher={Informa UK Limited}, author={Bonagura, J.D.}, year={1997}, month={Apr}, pages={2–3} }
 @article{lehmkuhl_bonagura_biller_hartman_1997, title={Radiographic evaluation of caudal vena cava size in dogs}, volume={38}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0031088654&partnerID=MN8TOARS}, number={2}, journal={Veterinary Radiology and Ultrasound}, author={Lehmkuhl, L.B. and Bonagura, J.D. and Biller, D.S. and Hartman, W.M.}, year={1997}, pages={94–100} }
 @article{wildman_medeiros_hamlin_stills_jones_bonagura_1996, title={Aspects of cardiomyopathy in copper-deficient pigs: Electrocardiography, echocardiography, and ultrastructural findings}, volume={55}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0030467726&partnerID=MN8TOARS}, DOI={10.1007/BF02784168}, abstractNote={Pigs were made copper (Cu)-deficient to evaluate cardiac function and pathology, and electrocardiography. Fifteen-day-old pigs were fed a Cu-restricted diet over an 8 wk period and compared to Cu-adequate diet-fed pigs. Cardiac effects were examined concerning gross morphometry and ultrastructure, echocardiography, and electrocardiography, as well as serum cholesterol levels. The Cu-restricted diet-fed pigs exhibited a marked deceleration of growth and lower hematocrit, hemoglobin, and liver and serum Cu concentrations compared to the Cu-adequate diet-fed pigs. The Cu-restricted diet-fed pigs developed a significantly greater heart weight:body weight ratio, along with greater diastolic measures of ventricular wall and internal dimension relative to body weight. Electrocardiography in the Cu-restricted diet-fed pigs revealed one instance of electrical alternans and an intraventricular conduction disturbance and several instances of T-wave inversion. The Cu-restricted pigs also displayed a prolonged QT interval at the closure of study. Increased mitochondrial volume density and mitochondria:myofibril volume density ratio were observed in the Cu-restricted pig electron micrographs along with excessive lipid and glycogen inclusion and focal degradation of Z-lines, intercalated disk, and sarcomeres. Copper-restriction in young pigs results in cardiac pathology and electrical disturbances. These alterations are similar to those reported for young Cu-restricted rodents. Given then that many cardiac manifestations of developed Cu-deficiency appear conserved across specie lines, the potential for human disturbances in response to severe Cu-deficiency may be plausible.}, number={1-2}, journal={Biological Trace Element Research}, author={Wildman, R.E.C. and Medeiros, D.M. and Hamlin, R.L. and Stills, H. and Jones, D.A. and Bonagura, J.D.}, year={1996}, pages={55–70} }
 @article{park_legzczvnski_mccune_bonagura_1996, title={Echocardiocraphic studies of progression to congestive heart failure in lean male shhf/mcc - F acp rats}, volume={10}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-10544234732&partnerID=MN8TOARS}, number={3}, journal={FASEB Journal}, author={Park, S.C. and Legzczvnski, J. and McCune, S.A. and Bonagura, J.D.}, year={1996} }
 @article{cardiorespiratory effects of acepromazine maleate and buprenorphine hydrochloride in clinically normal dogs_1995, volume={56}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0028894568&partnerID=MN8TOARS}, number={1}, journal={American Journal of Veterinary Research}, year={1995}, pages={78–84} }
 @article{blissitt_bonagura_1995, title={Colour flow Doppler echocardiography in horses with cardiac murmurs.}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0029362011&partnerID=MN8TOARS}, number={19}, journal={Equine veterinary journal. Supplement}, author={Blissitt, K.J. and Bonagura, J.D.}, year={1995}, pages={82–85} }
 @article{blissitt_bonagura_1995, title={Colour flow Doppler echocardiography in normal horses.}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0029362153&partnerID=MN8TOARS}, number={19}, journal={Equine veterinary journal. Supplement}, author={Blissitt, K.J. and Bonagura, J.D.}, year={1995}, pages={47–55} }
 @article{lehmkuhl_bonagura_jones_stepien_1995, title={Comparison of catheterization and Doppler-derived pressure gradients in a canine model of subaortic stenosis}, volume={8}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0029362391&partnerID=MN8TOARS}, DOI={10.1016/S0894-7317(05)80374-8}, abstractNote={The relationship between Doppler-estimated and catheterization-measured pressure gradients was examined by repeated-measures linear regression analysis and difference plots in 15 dogs with naturally occurring subvalvular aortic stenosis. Thirty left ventricular outflow tract gradients were compared during sinus rhythm and 142 gradients during premature or postextrasystolic beats for the following pairs of data: (1) mean catheterization gradient versus mean Doppler gradient, (2) maximal instantaneous catheterization gradient versus maximal Doppler gradient, and (3) peak-to-peak catheterization gradient versus maximal Doppler gradient. The correlation between Doppler-derived and catheterization-derived pressure gradients was excellent (r=0.99; p<0.001) for the maximal instantaneous (sinus rhythm: standard error of the estimate [SEE]=5.7 mm Hg; premature and postextrasystolic beats: SEE=6.7 mm Hg) and mean gradients (sinus rhythm: SEE=3.6 mm Hg; premature and postextrasystolic beats: SEE=4.5 mm Hg). There was also a strong correlation between the peak-to-peak catheterization gradient and the maximal Doppler gradient (sinus rhythm: r=0.99, p<0.001, SEE=5.3 mm Hg; premature and postextrasystolic beats: r=0.97, p<0.001, SEE=7.2 mm Hg). Agreement between the two techniques was best for mean gradients and most disparate for the comparisons of maximal Doppler gradients and peak-to-peak catheterization gradients. The relationship between Doppler-estimated and catheterization-measured pressure gradients was examined by repeated-measures linear regression analysis and difference plots in 15 dogs with naturally occurring subvalvular aortic stenosis. Thirty left ventricular outflow tract gradients were compared during sinus rhythm and 142 gradients during premature or postextrasystolic beats for the following pairs of data: (1) mean catheterization gradient versus mean Doppler gradient, (2) maximal instantaneous catheterization gradient versus maximal Doppler gradient, and (3) peak-to-peak catheterization gradient versus maximal Doppler gradient. The correlation between Doppler-derived and catheterization-derived pressure gradients was excellent (r=0.99; p<0.001) for the maximal instantaneous (sinus rhythm: standard error of the estimate [SEE]=5.7 mm Hg; premature and postextrasystolic beats: SEE=6.7 mm Hg) and mean gradients (sinus rhythm: SEE=3.6 mm Hg; premature and postextrasystolic beats: SEE=4.5 mm Hg). There was also a strong correlation between the peak-to-peak catheterization gradient and the maximal Doppler gradient (sinus rhythm: r=0.99, p<0.001, SEE=5.3 mm Hg; premature and postextrasystolic beats: r=0.97, p<0.001, SEE=7.2 mm Hg). Agreement between the two techniques was best for mean gradients and most disparate for the comparisons of maximal Doppler gradients and peak-to-peak catheterization gradients.}, number={5 PART 1}, journal={Journal of the American Society of Echocardiography}, author={Lehmkuhl, L.B. and Bonagura, J.D. and Jones, D.E. and Stepien, R.L.}, year={1995}, pages={611–620} }
 @article{bonagura_blissitt_1995, title={Echocardiography.}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0029362161&partnerID=MN8TOARS}, number={19}, journal={Equine veterinary journal. Supplement}, author={Bonagura, J.D. and Blissitt, K.J.}, year={1995}, pages={5–17} }
 @article{blissitt_bonagura_1995, title={Pulsed wave Doppler echocardiography in normal horses.}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0029362013&partnerID=MN8TOARS}, number={19}, journal={Equine veterinary journal. Supplement}, author={Blissitt, K.J. and Bonagura, J.D.}, year={1995}, pages={38–46} }
 @article{fossum_miller_rogers_bonagura_meurs_1994, title={Chylothorax associated with right-sided heart failure in five cats.}, volume={204}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0028101550&partnerID=MN8TOARS}, number={1}, journal={Journal of the American Veterinary Medical Association}, author={Fossum, T.W. and Miller, M.W. and Rogers, K.S. and Bonagura, J.D. and Meurs, K.M.}, year={1994}, pages={84–89} }
 @article{lehmkuhl_bonagura_1994, title={Comparison of transducer placement sites for Doppler echocardiography in dogs with subaortic stenosis.}, volume={55}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0028376762&partnerID=MN8TOARS}, number={2}, journal={American journal of veterinary research}, author={Lehmkuhl, L.B. and Bonagura, J.D.}, year={1994}, pages={192–198} }
 @article{bonagura_1994, title={Echocardiography.}, volume={204}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0028773113&partnerID=MN8TOARS}, number={4}, journal={Journal of the American Veterinary Medical Association}, author={Bonagura, J.D.}, year={1994}, pages={516–522} }
 @article{bonagura_1994, title={Equine echocardiography}, volume={150}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0028537298&partnerID=MN8TOARS}, DOI={10.1016/s0007-1935(94)80033-2}, abstractNote={A partial atrioventricular septal defect, represented as a large ostium primum atrial septal defect and common (bridging) atrioventricular valve leaflets with cleft septal leaflet of the mitral valve, was diagnosed incidentally in a nine-year-old warmblood gelding used for show jumping. Initial examination findings and a three-year follow-up are documented in this report. The horse was first presented for the evaluation of chronic coughing. A left-sided, grade 4/6 holosystolic (band-shaped) murmur was identified along with a similar right-sided, grade 3/6 heart murmur. Echocardiography revealed a 6.4 cm diameter communication in the ventral atrial septum, considered an ostium primum atrial septal defect, with bidirectional shunting. A hypertrophic septomarginal trabecula, a thickened tricuspid valve, a cleft septal leaflet of the mitral valve, moderate mitral and tricuspid regurgitation likely related to leaflet prolapse, mild aortic regurgitation, and signs of moderate right ventricular volume overload were found as well. Electrocardiography showed no arrhythmias neither at rest nor during treadmill exercise. The owner continued to use the horse for show jumping. No exercise intolerance or other signs of disease were noted. Follow-up examination was performed three years after initial presentation. Contrast echocardiography confirmed the presence of right-to-left shunting through the atrial septal defect. Compared with the initial examination, the left ventricular internal diameter on M-mode echocardiography had increased. Occasional ventricular premature depolarizations were noted on the resting and exercise electrocardiogram. This is the first description of a clinically asymptomatic partial atrioventricular septal defect in an adult sport horse.}, number={6}, journal={British Veterinary Journal}, publisher={Elsevier BV}, author={Bonagura, J.D.}, year={1994}, month={Nov}, pages={503–506} }
 @article{lehmkuhl_ware_bonagura_1994, title={Mitral Stenosis in 15 Dogs}, volume={8}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0028249092&partnerID=MN8TOARS}, DOI={10.1111/j.1939-1676.1994.tb03190.x}, abstractNote={Mitral stenosis was diagnosed in 15 young to middle-aged dogs. There were 5 Newfoundlands and 4 bull terriers affected, suggesting a breed predisposition for this disorder. Clinical signs included cough, dyspnea, exercise intolerance, and syncope. Soft left apical diastolic murmurs were heard only in 4 dogs, whereas 8 dogs had systolic murmurs characteristic of mitral regurgitation. Left atrial enlargement was the most prominent radiographic feature. Left-sided congestive heart failure was detected by radiographs in 11 dogs within 1 year of diagnosis. Electrocardiographic abnormalities varied among dogs and included atrial and ventricular enlargement, as well as atrial and ventricular arrhythmias. Abnormalities on M-mode and two-dimensional echocardiograms included abnormal diastolic motion of the mitral valve characterized by decreased leaflet separation, valve doming, concordant motion of the parietal mitral valve leaflet, and a decreased E-to-F slope. Increased mitral valve inflow velocities and prolonged pressure half-times were detected by Doppler echocardiography. Cardiac catheterization, performed in 8 dogs, documented a diastolic pressure gradient between the left atrial, pulmonary capillary wedge, or pulmonary artery diastolic pressures and the left ventricular diastolic pressure. Necropsy showed mitral stenosis caused by thickened, fused mitral valve leaflets in 5 dogs and a supramitral ring in another dog. The outcome in affected dogs was poor; 9 of 15 dogs were euthanatized or died by 2 1/2 years of age.}, number={1}, journal={Journal of Veterinary Internal Medicine}, author={Lehmkuhl, L.B. and Ware, W.A. and Bonagura, J.D.}, year={1994}, pages={2–17} }
 @article{simpson_bonagura_eaton_1994, title={Right Ventricular Cardiomyopathy in a Dog}, volume={8}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0028478214&partnerID=MN8TOARS}, DOI={10.1111/j.1939-1676.1994.tb03240.x}, abstractNote={Journal of Veterinary Internal MedicineVolume 8, Issue 4 p. 306-309 Open Access Right Ventricular Cardiomyopathy in a Dog Kenneth W. Simpson, Kenneth W. Simpson Departments of Veterinary Clinical Sciences and Pathobiology, College of Veterinary Medicine, The Ohio State University, Columbus, OHSearch for more papers by this authorJohn D. Bonagura, John D. Bonagura Departments of Veterinary Clinical Sciences and Pathobiology, College of Veterinary Medicine, The Ohio State University, Columbus, OH Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 601 Tharp St, Columbus, OH 43210–1089.Search for more papers by this authorKathryn A. Eaton, Kathryn A. Eaton Departments of Veterinary Clinical Sciences and Pathobiology, College of Veterinary Medicine, The Ohio State University, Columbus, OHSearch for more papers by this author Kenneth W. Simpson, Kenneth W. Simpson Departments of Veterinary Clinical Sciences and Pathobiology, College of Veterinary Medicine, The Ohio State University, Columbus, OHSearch for more papers by this authorJohn D. Bonagura, John D. Bonagura Departments of Veterinary Clinical Sciences and Pathobiology, College of Veterinary Medicine, The Ohio State University, Columbus, OH Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 601 Tharp St, Columbus, OH 43210–1089.Search for more papers by this authorKathryn A. Eaton, Kathryn A. Eaton Departments of Veterinary Clinical Sciences and Pathobiology, College of Veterinary Medicine, The Ohio State University, Columbus, OHSearch for more papers by this author First published: July 1994 https://doi.org/10.1111/j.1939-1676.1994.tb03240.xCitations: 17 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Rose BD. Hypo-osmolal states-Hyponatremia. In: Clinical Physiology of Acid Base and Electrolyte Balance, 3rd ed. New York , NY : McGraw Hill; 1989: pp 601–638. 2 Rose BD. Nephrology forum: Diuretics. Kidney Int 1991; 39: 336–352. 3 Marcus IF, Fontaine GH, Guirardon G., et al. Right ventricular dysplasia: A report of 24 adult cases. Circulation 1982; 65: 384–398. 4 Thiene G., Nava A., Corrado D., et al. Right ventricular cardiomyopathy and sudden death in young people. New Engl J Med 1988; 38: 129–133. 5 Ibsen HHW, Baandrup U., Simonsen EE. Familial right ventricular dilated cardiomyopathy. Br Heart J 1985; 54: 156–159. 6 Pinamonti B., Salvi A., Silvestri F., et al. Left ventricular involvement in right ventricular cardiomyopathy. Eur Heart J 1989; 10(suppl D): 20–21. 7 Detweiler DK. Spontaneous and induced arterial disease in the dog: Pathology and pathogenesis. Toxicol-Pathol 1989; 17: 94–108. 8 Mettauer B., Rouleau J-L, Bichet D., et al. Sodium and water excretion abnormalities in congestive heart failure: Determinant factors and clinical implications. Ann Intern Med 1986; 105: 161–167. 9 Dzau VJ, Hollenberg NK. Renal response to captopril in severe heart failure: Role of furosemide in natriuresis and reversal of hyponatremia. Ann Intern Med 1984; 100: 777–782. 10 Friedman E., Shadel M., Halkin H., et al. Thiazide induced hyponatremia: Reproducibility by single dose challenge and an analysis of pathogenesis. Ann Intern Med 1989; 110: 24–30. Citing Literature Volume8, Issue4July 1994Pages 306-309 ReferencesRelatedInformation}, number={4}, journal={Journal of Veterinary Internal Medicine}, author={Simpson, K.W. and Bonagura, J.D. and Eaton, K.A.}, year={1994}, pages={306–309} }
 @article{darke_bonagura_miller_1993, title={Transducer orientation for Doppler echocardiography in dogs}, volume={34}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84985315632&partnerID=MN8TOARS}, DOI={10.1111/j.1748-5827.1993.tb02564.x}, abstractNote={ABSTRACT The orientation of an ultrasound transducer required to provide standard echocardiographic views of the heart valves that would permit optimal alignment with blood flow for pulsed‐wave Doppler studies, was investigated in 20 normal dogs. Orientation was defined by the site on the thoracic wall at which the transducer was placed and by the angulation and rotation required to produce a two‐dimensional image in which the pulsed‐wave Doppler beam could be aligned with flow through each of the four heart valves. Two views, each a relatively short‐axis projection at the heart base, from either side of the thorax, gave alignment with the pulmonary artery. Three views gave reliable alignment with the aortic valve, from the cardiac apex on each side of the thorax and subcostally. One view was available for the mitral and tricuspid valves, from the left side of the thorax. Definition of these sites should help clinicians and technicians to develop a systematic routine for Doppler investigations in dogs and facilitate communication between investigators.}, number={1}, journal={Journal of Small Animal Practice}, author={Darke, P.G.G. and Bonagura, J.D. and Miller, M.}, year={1993}, pages={2–8} }
 @article{long_bonagura_darke_1992, title={Standardised imaging technique for guided M‐mode and Doppler echocardiography in the horse}, volume={24}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0026862871&partnerID=MN8TOARS}, DOI={10.1111/j.2042-3306.1992.tb02820.x}, abstractNote={Summary Eighteen echocardiographic images useful for diagnostic imaging, M‐mode echocardiography, and Doppler echocardiography of the equine heart were standardised by relating the position of the axial beam to various intracardiac landmarks. The transducer orientation required for each image was recorded in 14 adult horses by describing the degree of sector rotation and the orientation of the axial beam relative to the thorax. Repeatable images could be obtained within narrow limits of angulation and rotation for 14 of the 18 standardised images evaluated. Twenty‐seven National Hunt horses were subsequently examined using this standardised technique. Selected cardiac dimensions were measured from two‐dimensional and guided M‐mode studies. Satisfactory results were achieved in 26 of the 27 horses. There was no linear correlation between any of the measured cardiac values and bodyweight. There was no significant difference between measurements taken from the left and the right hemithorax. Six horses were imaged on three consecutive days to assess the repeatability of the measurements. No significant difference was found between measurements obtained on different days. This study demonstrates a method for standardised echocardiographic evaluation of the equine heart that is repeatable, valuable for teaching techniques of equine echocardiography, applicable for diagnostic imaging and quantification of cardiac size, and useful for the evaluation of blood‐flow patterns by Doppler ultrasound.}, number={3}, journal={Equine Veterinary Journal}, author={LONG, K.J. and BONAGURA, J.D. and DARKE, P.G.G.}, year={1992}, pages={226–235} }
 @article{ciulla_meazza_reggiani_bonagura_vandoni_magrini_1991, title={24. Electrocardiographic evidence of left ventricular hypertrophy in young spontaneously hypertensive rats}, volume={9}, DOI={10.1097/00004872-199112000-00215}, number={6}, journal={Journal of Hypertension}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Ciulla, M. and Meazza, R. and Reggiani, P. and Bonagura, F. and Vandoni, P. and Magrini, F.}, year={1991}, pages={S431} }
 @article{stepien_bonagura_1991, title={Aortic stenosis: clinical findings in six cats}, volume={32}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84985354664&partnerID=MN8TOARS}, DOI={10.1111/j.1748-5827.1991.tb00945.x}, abstractNote={ABSTRACT Congenital aortic stenosis was diagnosed in six cats. Clinical findings included dyspnoea, systolic murmurs with maximal intensity at the left apex or right sternal border, and cardiomegaly with congestive heart failure. Some clinical features of feline aortic stenosis were similar to those observed in cats with hypertrophic cardiomyopathy. Definitive diagnosis was obtained by angiographic imaging of a discrete, consistent subvalvular obstruction, Doppler‐echocardio‐graphy, or by necropsy. Although, two of the cats were diagnosed at ages older than usually reported, the overall prognosis for cats with aortic stenosis was poor. Four of the six cats died or were euthanased within one year of the onset of clinical signs.}, number={7}, journal={Journal of Small Animal Practice}, author={Stepien, R.L. and Bonagura, J.D.}, year={1991}, pages={341–350} }
 @article{sisson_knight_helinski_fox_bond_harpster_moise_kaplan_bonagura_czarnecki_et al._1991, title={Plasma Taurine Concentrations and M‐mode Echocardiographic Measures in Healthy Cats and in Cats with Dilated Cardiomyopathy}, volume={5}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0026197971&partnerID=MN8TOARS}, DOI={10.1111/j.1939-1676.1991.tb00954.x}, abstractNote={M‐mode echocardiography was completed and plasma taurine concentrations were determined in 79 healthy cats and 77 cats with dilated cardiomyopathy (DCM). In healthy cats, a relationship was not observed between plasma taurine concentrations and any M‐mode echocardiographic measurement. End‐systolic and end‐diastolic cardiac chamber dimensions were larger; wall thickness measures were smaller; and calculations of fractional shortening were less in cats with DCM than in healthy cats. Plasma taurine concentrations < 30 nmol/mL were detected in 7/79 healthy cats and in 52/77 cats with DCM. Of the 52 cats with DCM and an initial plasma taurine concentration < 30 nmol/mL, 23 died or were euthanized during the first post‐treatment week, 7 were lost to further study, and 22 improved after taurine supplementation. Of the 25 cats with DCM and an initial plasma taurine concentration > 30 nmol/mL, 9 died or were euthanatized during the first post‐treatment week, and 9 were lost to further study. Two cats did not improve, of which one died and one was euthanatized 4 to 8 weeks after initiation of taurine supplementation. Five cats with a plasma taurine concentration > 30 nmol/mL improved after taurine supplementation. Myocardial function subsequently deteriorated in three of these cats. Two of the three cats had signs of congestive heart failure redevelop.}, number={4}, journal={Journal of Veterinary Internal Medicine}, author={Sisson, D.D. and Knight, D.H. and Helinski, C. and Fox, P.R. and Bond, B.R. and Harpster, N.K. and Moise, N.S. and Kaplan, P.M. and Bonagura, J.D. and Czarnecki, G. and et al.}, year={1991}, pages={232–238} }
 @article{clinical and electrocardiographic characterization of cattle with atrial premature complexes._1990, volume={197}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0025520717&partnerID=MN8TOARS}, number={9}, journal={Journal of the American Veterinary Medical Association}, year={1990}, pages={1163–1169} }
 @article{bonagura_1990, title={Clinical evaluation and management of heart disease}, volume={2}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84982055357&partnerID=MN8TOARS}, DOI={10.1111/j.2042-3292.1990.tb01376.x}, abstractNote={Equine Veterinary EducationVolume 2, Issue 1 p. 31-37 Clinical evaluation and management of heart disease J. D. Bonagura, J. D. Bonagura Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio 43210-1089, USA.Search for more papers by this author J. D. Bonagura, J. D. Bonagura Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio 43210-1089, USA.Search for more papers by this author First published: March 1990 https://doi.org/10.1111/j.2042-3292.1990.tb01376.xCitations: 19AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume2, Issue1March 1990Pages 31-37 RelatedInformation}, number={1}, journal={Equine Veterinary Education}, publisher={Wiley}, author={Bonagura, J. D.}, year={1990}, month={Mar}, pages={31–37} }
 @article{keister_kittleson_bonagura_pipers_knauer_1990, title={Milrinone: A Clinical Trial in 29 Dogs With Moderate to Severe Congestive Heart Failure}, volume={4}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0025391430&partnerID=MN8TOARS}, DOI={10.1111/j.1939-1676.1990.tb03107.x}, abstractNote={Milrinone, a positive inotropic drug with vasodilating properties, was administered at doses of 0.5 to 1 mg/kg orally twice daily to 29 dogs with moderateto severe congestive heart failure (CHF). Significant echocardiographic improvement in ventricular systolic function was observed after 3 days of administration of milrinone and at the patients' last echocardiographic observation (day 21in 25 subjects, day 7 in 2 subjects, and day 3 in 2 subjects). Echocardiographic shortening fraction at the initial measurement had a median increase of 6.14%( P < 0.001), and for the last observation a 2.83% increase ( P < 0.005). Most patients also showed improvement in their clinical signs as assessed by the veterinarian (72%) and by owner's evaluation (81%). No consistent problem or adverse reaction to milrinone was observed, except for a small number ofclinically manageable ventricular dysrhythmias. Milrinone appears in this trialto be effective for the treatment of advanced CHF in dogs.}, number={2}, journal={Journal of Veterinary Internal Medicine}, author={Keister, D.M. and Kittleson, M.D. and Bonagura, J.D. and Pipers, F.S. and Knauer, K.W.}, year={1990}, pages={79–86} }
 @article{birchard_bonagura_fingland_1990, title={Results of ligation of patent ductus arteriosus in dogs: 201 cases (1969-1988).}, volume={196}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0025707932&partnerID=MN8TOARS}, number={12}, journal={Journal of the American Veterinary Medical Association}, author={Birchard, S.J. and Bonagura, J.D. and Fingland, R.B.}, year={1990}, pages={2011–2013} }
 @article{miller_bonagura_dibartola_fossum_1989, title={Budd-Chiari-like syndrome in two dogs}, volume={25}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0024519485&partnerID=MN8TOARS}, number={3}, journal={Journal of the American Animal Hospital Association}, author={Miller, M.W. and Bonagura, J.D. and DiBartola, S.P. and Fossum, T.W.}, year={1989}, pages={277–283} }
 @article{miller_bonagura_1989, title={ECG of the month. Atrial premature complexes and paroxysmal atrial tachycardia.}, volume={194}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0024655451&partnerID=MN8TOARS}, number={7}, journal={Journal of the American Veterinary Medical Association}, author={Miller, M.W. and Bonagura, J.D.}, year={1989}, pages={906–907} }
 @article{binkley_bonagura_olson_boudoulas_wooley_1987, title={The equilibrium position of the mitral valve: An accurate model of mitral valve motion in humans}, volume={59}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0023240721&partnerID=MN8TOARS}, DOI={10.1016/S0002-9149(87)80081-4}, abstractNote={A “semiopen” diastolic equilibrium position of the mitral valve that is assumed in the absence of transmitral flow has been demonstrated in instrumented dogs. It has been suggested that the papillary muscles and chordae tendineae play an integral role in returning the valve to this position after initial diastolic opening. To determine whether such a model of mitral valve motion is valid in noninstrumented humans without underlying valvular disease, M-mode and Doppler ultrasound studies were performed in 6 subjects who underwent prolonged periods of ventricular diastole and atrial inactivity. After maximal opening, the mitral valve assumed a stable open position in which mean separation of the anterior and posterior mitral leaflets was 52% of maximal separation. This position was maintained for a mean duration of 585 ms, during which time transmitral flow fell to 0 m/s. Peak mitral valve opening preceded the early transmitral flow peak by an average of 42 ms, suggesting an active closure of the mitral valve as flow continued to accelerate. It is concluded that a semiopen equilibrium position of the mitral valve is assumed during prolonged diastolic periods in the absence of transmitral flow and is an accurate model describing diastolic mitral valve motion in noninstrumented humans. The chordae tendineae and papillary muscles may actively participate in the genesis and maintenance of the equilibrium position. A “semiopen” diastolic equilibrium position of the mitral valve that is assumed in the absence of transmitral flow has been demonstrated in instrumented dogs. It has been suggested that the papillary muscles and chordae tendineae play an integral role in returning the valve to this position after initial diastolic opening. To determine whether such a model of mitral valve motion is valid in noninstrumented humans without underlying valvular disease, M-mode and Doppler ultrasound studies were performed in 6 subjects who underwent prolonged periods of ventricular diastole and atrial inactivity. After maximal opening, the mitral valve assumed a stable open position in which mean separation of the anterior and posterior mitral leaflets was 52% of maximal separation. This position was maintained for a mean duration of 585 ms, during which time transmitral flow fell to 0 m/s. Peak mitral valve opening preceded the early transmitral flow peak by an average of 42 ms, suggesting an active closure of the mitral valve as flow continued to accelerate. It is concluded that a semiopen equilibrium position of the mitral valve is assumed during prolonged diastolic periods in the absence of transmitral flow and is an accurate model describing diastolic mitral valve motion in noninstrumented humans. The chordae tendineae and papillary muscles may actively participate in the genesis and maintenance of the equilibrium position.}, number={1}, journal={The American Journal of Cardiology}, author={Binkley, P.F. and Bonagura, J.D. and Olson, S.M. and Boudoulas, H. and Wooley, C.F.}, year={1987}, pages={109–113} }
 @article{bonagura_ware_1986, title={Atrial fibrillation in the dog: Clinical findings in 81 cases}, volume={22}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0022598156&partnerID=MN8TOARS}, number={1}, journal={Journal of the American Animal Hospital Association}, author={Bonagura, J.D. and Ware, W.A.}, year={1986}, pages={111–120} }
 @article{bonagura_miller_1986, title={Common conduction disturbances}, volume={6}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882501301&partnerID=MN8TOARS}, DOI={10.1016/s0737-0806(86)80076-4}, abstractNote={Electrocardiographic T-wave morphology is used in drug safety studies as an adjunct to the QTc interval, but few measurements of T-wave morphology can be interpreted in clinical practice. Morphology combination score (MCS) is a combination of T-wave flatness/peakedness, asymmetry, and notching, enabling easy visual assessment of T-wave morphology. We aimed to test the association between T-wave morphology, quantified by MCS, and mortality.We included electrocardiograms recorded in 2001–2011 from 342,294 primary care patients. Using Cox regression, we evaluated the association between MCS, cardiovascular death, and all-cause mortality, adjusting for heart rate, QTc, QT-prolonging drugs, diabetes, ischemic heart disease, hypertension, and congestive heart failure.270,039 individuals (44% men, median age 55 [inter-quartile range: 42–67 years]) were included and followed for a median of 9.3 years, during which time 13,489 (5.0%) died from cardiovascular causes and 50,481 (18.7%) from any cause. High values of MCS (i.e. asymmetric, flattened, and/or notched T waves) were associated with an adjusted mortality Hazard Ratio of 1.75 (95% CI 1.62–1.89) and 1.61 (1.43–1.92) for women and men, respectively. Low values of MCS (i.e. peaked and symmetric T waves) were associated with a Hazard Ratio of 1.18 (1.08–1.28) and 1.71 (1.48–1.98) for women and men, respectively.In a large primary care population, we found that T-wave asymmetry, flatness, and notching provided prognostic information on mortality independent of heart rate, QTc, and baseline comorbidities.}, number={1}, journal={Journal of Equine Veterinary Science}, publisher={Elsevier BV}, author={Bonagura, John D. and Miller, Michael S.}, year={1986}, month={Jan}, pages={23–25} }
 @article{ware_bonagura_rings_1986, title={Echocardiographic diagnosis of pulmonic valve vegetative endocarditis in a cow.}, volume={188}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0023048919&partnerID=MN8TOARS}, number={2}, journal={Journal of the American Veterinary Medical Association}, author={Ware, W.A. and Bonagura, J.D. and Rings, D.M.}, year={1986}, pages={185–187} }
 @article{fingland_bonagura_myer_1986, title={Pulmonic stenosis in the dog: 29 cases (1975-1984).}, volume={189}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0023049889&partnerID=MN8TOARS}, number={2}, journal={Journal of the American Veterinary Medical Association}, author={Fingland, R.B. and Bonagura, J.D. and Myer, C.W.}, year={1986}, pages={218–226} }
 @article{o’grady_bonagura_powers_herring_1986, title={QUANTITATIVE CROSS‐SECTIONAL ECHOCARDIOGRAPHY IN THE NORMAL DOG}, volume={27}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84882102854&partnerID=MN8TOARS}, DOI={10.1111/j.1740-8261.1986.tb00001.x}, abstractNote={Two‐dimensional echocardiography was performed on 18 unanesthetized, normal dogs (4.5 to 30 kg). Measurements of wall thickness, intracavitary dimensions, and cross‐sectional area of the left atrium, left ventricle, and aorta were made. Satisfactory data were obtained from 17 dogs, and were used to determine normal values. Normal data were tested for significant correlation to body weight (kg) by linear regression. Repeatability was studied in six dogs examined, on three separate occasions, during a 5‐day period. Differences between values obtained on different days were evaluated by analysis of variance. Satisfactory qualitative echocardiograms were repeatedly obtained by using consistent sites of transducer placement and by identifying internal cardiac structures. These tomographic planes were highly reproducible, with only ventricular length, and some views of the ventricular septum, showing statistically significant (P < 0.05) differences. Almost all linear and area measurements were significantly correlated to body size, while most indices of left ventricular function were independent of body weight. Dimensions obtained from the left and right parasternal position were nearly identical. Cross‐sectional echocardiography allows repeatable assessment of cardiac anatomy, and it should prove useful for identification and quantitation of heart disease in the dog.}, number={2}, journal={Veterinary Radiology}, author={O’Grady, M.R. and Bonagura, J.D. and Powers, J.D. and Herring, D.S.}, year={1986}, pages={34–49} }
 @article{miller_bonagura_1985, title={Atrial arrhythmias}, volume={5}, DOI={10.1016/s0737-0806(85)80073-3}, number={5}, journal={Journal of Equine Veterinary Science}, publisher={Elsevier BV}, author={Miller, Michael S. and Bonagura, John D.}, year={1985}, month={Jan}, pages={300–304} }
 @article{johnson_rogers_bonagura_caldwell_1985, title={Determination of serum bile acids in fasting dogs with hepatobiliary disease.}, volume={46}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0022135825&partnerID=MN8TOARS}, number={10}, journal={American Journal of Veterinary Research}, author={Johnson, S.E. and Rogers, W.A. and Bonagura, J.D. and Caldwell, J.H.}, year={1985}, pages={2048–2053} }
 @article{bonagura_herring_welker_1985, title={Echocardiography}, volume={1}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0022109475&partnerID=MN8TOARS}, DOI={10.1016/s0749-0739(17)30758-7}, abstractNote={Diagnostic ultrasound permits the clinician to image the beating heart, quantitate cardiac dimensions, identify specific congenital and acquired cardiac lesions, and estimate the degree of cardiac compensation and muscle failure that accompanies a specific lesion. The M-mode (motion) echocardiogram and two-dimensional echocardiogram are complementary studies that have proved useful for identification of cardiac septal defects, endocarditis, pericardial effusion, intracardiac shunting, cardiomegaly, and heart muscle failure. Appreciation of the technique and basic knowledge of the types of information that can be obtained from echocardiography are necessary to appropriately refer horses for these studies.}, number={2}, journal={Veterinary Clinics of North America: Equine Practice}, publisher={Elsevier BV}, author={Bonagura, John D. and Herring, David S. and Welker, Frank}, year={1985}, month={Aug}, pages={311–333} }
 @article{bonagura_herring_1985, title={Echocardiography. Acquired heart disease.}, volume={15}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0022155740&partnerID=MN8TOARS}, DOI={10.1016/S0195-5616(85)50366-6}, abstractNote={Acquired disease of the cardiac valves, myocardium, and pericardium may be recognized through echocardiography. Quantitation of atrial and ventricular dimensions is a key aspect in the echocardiographic evaluation of acquired heart diseases. Subjective interpretation permits identification of pericardial effusion, dilated cardiomyopathy, valvular lesions, cardiac masses, and abnormal blood flow.}, number={6}, journal={The Veterinary clinics of North America. Small animal practice}, author={Bonagura, J.D. and Herring, D.S.}, year={1985}, pages={1209–1224} }
 @article{bonagura_herring_1985, title={Echocardiography. Congenital heart disease.}, volume={15}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0022154915&partnerID=MN8TOARS}, DOI={10.1016/S0195-5616(85)50365-4}, abstractNote={Echocardiography can be used to identify malformations of the heart and to assess the degree of cardiac compensation that occurs with congenital heart disease. Integration of clinical and ultrasound data will generally allow a diagnosis to be made noninvasively. Contrast echocardiography may delineate intracardiac shunting.}, number={6}, journal={The Veterinary clinics of North America. Small animal practice}, author={Bonagura, J.D. and Herring, D.S.}, year={1985}, pages={1195–1208} }
 @article{echocardiography. principles of interpretation._1985, volume={15}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0022156843&partnerID=MN8TOARS}, DOI={10.1016/S0195-5616(85)50364-2}, abstractNote={Echocardiography offers the clinician an opportunity to image the heart noninvasively. Both M-mode and cross-sectional echocardiography can be used to measure cardiac dilation and hypertrophy and to quantitate myocardial function. Knowledge of normal echocardiographic anatomy is essential for understanding changes that occur in disease.}, number={6}, journal={The Veterinary clinics of North America. Small animal practice}, year={1985}, pages={1177–1194} }
 @article{bonagura_1985, title={Equine heart disease. An overview.}, volume={1}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0022109664&partnerID=MN8TOARS}, number={2}, journal={The Veterinary clinics of North America. Equine practice}, author={Bonagura, J.D.}, year={1985}, pages={267–288} }
 @article{bonagura_1985, title={Foreword}, volume={1}, DOI={10.1016/s0749-0739(17)30754-x}, number={2}, journal={Veterinary Clinics of North America: Equine Practice}, publisher={Elsevier BV}, author={Bonagura, John D.}, year={1985}, month={Aug}, pages={265} }
 @article{bonagura_miller_1985, title={Junctional and ventricular arrhythmias}, volume={5}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-34447137203&partnerID=MN8TOARS}, DOI={10.1016/s0737-0806(85)80008-3}, number={6}, journal={Journal of Equine Veterinary Science}, publisher={Elsevier BV}, author={Bonagura, John D. and Miller, Michael S.}, year={1985}, month={Jan}, pages={347–350} }
 @article{miller_bonagura_1985, title={Normal ECG complexes}, volume={5}, DOI={10.1016/s0737-0806(85)80097-6}, abstractNote={The chapter provides an overview of blood in birds. The composition and roles of avian plasma is considered. This includes the circulating electrolytes, nutrients (e.g. glucose, amino acids), and other small organic molecules (e.g. uric acid and urea). Moreover, the concentrations, composition, and roles of the multiple plasma proteins are discussed. This encompasses the roles of specific transport proteins such as transferrin, ceruloplasmin, insulin-like growth factor binding proteins, and retinol-binding protein. Furthermore, avian immunoglobulins are discussed. The structure of erythrocytes of birds is outlined. Unlike the situation in most mammals, avian erythrocytes have nuclei. Consideration is given to erythrocyte transcription, lifespan, production including the role of the stimulatory hormone—avian erythropoietin, metabolism, and number. The erythrocyte functions to transport oxygen bound to hemoglobin and to facilitate carbon dioxide transport by the enzyme, carbonic anhydrase generating carbonic acid and hence bicarbonate ions. The role of hemoglobin is discussed including adaptations to high altitudes and shifts during embryonic development. Essential to the transport of carbon dioxide are the anion transporters and the sodium/potassium transporter. Avian blood contains leukocytes and thrombocytes. There are five types of leukocytes, namely: heterophils, lymphocytes, monocytes, eosinophils, and basophils. The structure, number, production, and functions of these are discussed. Unlike the situation in mammals, avian thrombocytes are nucleated cells. As would be expected, these function to cause blood clotting. In addition, they have a series of immune functions. Avian blood is employed in biomedical models including β-adrenergic receptors, transgenic chickens, the avian IgY antibodies, and nutritional models.}, number={4}, journal={Journal of Equine Veterinary Science}, publisher={Elsevier BV}, author={Miller, Michael S. and Bonagura, John D.}, year={1985}, month={Jan}, pages={200–203} }
 @article{normal and paradoxical ventricular septal motion in the dog._1985, volume={46}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0022120108&partnerID=MN8TOARS}, number={9}, journal={American Journal of Veterinary Research}, year={1985}, pages={1832–1841} }
 @article{miller_bonagura_1985, title={Normal cardiac rhythms}, volume={5}, DOI={10.1016/s0737-0806(85)80020-4}, abstractNote={Orthopaedic, or other, injuries in sports medicine can be quantified using the ‘days-lost to training’ concept. Both the training regimen and the surface used in training and racing can affect the health of racehorses. Our aim was to associate ‘days-lost to training’ in elite-level show-jumpers to horse characteristics, training and management strategies, and the time spent working on various training and competition surfaces. We designed a longitudinal study of professional riders in four European countries. Data were recorded using training diaries. Reasons for days-lost were classified into non-acute and acute orthopaedic, medical, hoof-related, and undefined. We produced descriptive statistics of training durations, relative to type of training, surfaces used, and days-lost. We created zero-inflated negative-binomial random-effects models using the overall days-lost as outcome. In the whole dataset, duration variables related to training surfaces were analysed as independent. The Swedish data only were also used to test whether duration variables were related to competition surfaces.Thirty-one riders with 263 horses provided data on 39,028 days at risk. Of these, 2357 (6.0%) were days-lost (55% and 22% of these were due to non-acute and acute orthopaedic injuries, respectively) in 126 horses.In the all-country model, controlling for season, a significant variable was country. Switzerland and the UK had lower incidence-rate ratios (IR) compared to Sweden (IRs 0.2 and 0.03, respectively). Horses with previous orthopaedic problems had almost a doubled IR (1.8) of days-lost due to orthopaedic injury, compared to baseline. If the horse had jumping training more than 1 min per day at risk the IRs were 6.9–7 (compared to less than this amount of time); this was, however, likely an effect of a small baseline. Variation in training was a protective factor with a dose–response relationship; the category with the highest variation had an IR of 0.1.In the Swedish model, controlling for season, there was an association of year (IR 2.8 year 2010). Further, if the horse rested >17–25% of the days at risk, or >33% of the DAR2, had IRs 3.5 and 3.0, compared to less time. Horses ≥6 years had IRs of 1.8–2.0, compared to younger horses. Limited training use of sand surface was a risk-factor (IR 2.2; >4 ≤ 12 min/day at risk), compared to not training on sand. Training/competing on sand-wood was a protective factor (IRs 0.4–0.5) compared to not using this surface.}, number={3}, journal={Journal of Equine Veterinary Science}, publisher={Elsevier BV}, author={Miller, Michael S. and Bonagura, John D.}, year={1985}, month={Jan}, pages={157–159} }
 @article{miller_bonagura_1985, title={What is your diagnosis?}, volume={5}, DOI={10.1016/s0737-0806(85)80080-0}, number={1}, journal={Journal of Equine Veterinary Science}, publisher={Elsevier BV}, author={Miller, Michael S. and Bonagura, John D.}, year={1985}, month={Jan}, pages={23} }
 @article{muir_bonagura_1984, title={Treatment of cardiac arrhythmias in dogs with gastric distention-volvulus}, volume={184}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0021237084&partnerID=MN8TOARS}, number={11}, journal={Journal of the American Veterinary Medical Association}, author={Muir, W.W. and Bonagura, J.D.}, year={1984}, pages={1366–1371} }
 @article{bonagura_helphrey_muir_1983, title={Complications associated with permanent pacemaker implantation in the dog}, volume={182}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0020683468&partnerID=MN8TOARS}, number={2}, journal={Journal of the American Veterinary Medical Association}, author={Bonagura, J.D. and Helphrey, M.L. and Muir, W.W.}, year={1983}, pages={149–155} }
 @article{bonagura_pipers_1983, title={Diagnosis of cardiac lesions by contrast echocardiography.}, volume={182}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0021103522&partnerID=MN8TOARS}, number={4}, journal={Journal of the American Veterinary Medical Association}, author={Bonagura, J.D. and Pipers, F.S.}, year={1983}, pages={396–402} }
 @article{ecg of the month. muscular dystrophy with involvement of sinoatrial and atrioventricular nodal tissues._1983, volume={183}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0021104868&partnerID=MN8TOARS}, number={6}, journal={Journal of the American Veterinary Medical Association}, year={1983}, pages={658–659} }
 @article{bonagura_dibartola_1983, title={ECG of the month. Sick sinus syndrome.}, volume={183}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0021104733&partnerID=MN8TOARS}, number={4}, journal={Journal of the American Veterinary Medical Association}, author={Bonagura, J.D. and DiBartola, S.P.}, year={1983}, pages={420–421} }
 @article{bonagura_pipers_1983, title={Echocardiographic features of aortic valve endocarditis in a dog, a cow, and a horse.}, volume={182}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0021103694&partnerID=MN8TOARS}, number={6}, journal={Journal of the American Veterinary Medical Association}, author={Bonagura, J.D. and Pipers, F.S.}, year={1983}, pages={595–599} }
 @article{bonagura_1983, title={M-mode echocardiography. Basic principles.}, volume={13}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0020755004&partnerID=MN8TOARS}, DOI={10.1016/S0195-5616(83)50031-4}, number={2}, journal={The Veterinary clinics of North America. Small animal practice}, author={Bonagura, J.D.}, year={1983}, pages={299–319} }
 @article{bonagura_myer_pensinger_1982, title={Angiocardiography}, volume={12}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0020135313&partnerID=MN8TOARS}, DOI={10.1016/s0195-5616(82)50030-7}, number={2}, journal={Veterinary Clinics of North America: Small Animal Practice}, publisher={Elsevier BV}, author={Bonagura, John D. and Myer, C. Wendy and Pensinger, Robert R.}, year={1982}, month={May}, pages={239–258} }
 @article{muir_bonagura_1982, title={Aprindine for treatment of ventricular arrhythmias in the dog}, volume={43}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0020435914&partnerID=MN8TOARS}, number={10}, journal={American Journal of Veterinary Research}, author={Muir, W.W. and Bonagura, J.D.}, year={1982}, pages={1815–1819} }
 @article{bonagura_1982, title={Fluid and electrolyte management of the cardiac patient.}, volume={12}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0020170958&partnerID=MN8TOARS}, DOI={10.1016/S0195-5616(82)50058-7}, number={3}, journal={The Veterinary clinics of North America. Small animal practice}, author={Bonagura, J.D.}, year={1982}, pages={501–513} }
 @article{myer_bonagura_1982, title={Survey radiography of the heart.}, volume={12}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0020136038&partnerID=MN8TOARS}, number={2}, journal={The Veterinary clinics of North America. Small animal practice}, author={Myer, C.W. and Bonagura, J.D.}, year={1982}, pages={213–237} }
 @article{bonagura_1981, title={Cardiopulmonary Disorders in the Geriatric Dog}, volume={11}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0019641722&partnerID=MN8TOARS}, DOI={10.1016/s0195-5616(81)50082-9}, number={4}, journal={Veterinary Clinics of North America: Small Animal Practice}, publisher={Elsevier BV}, author={Bonagura, John D.}, year={1981}, month={Nov}, pages={705–726} }
 @article{pipers_bonagura_hamlin_kittleson_1981, title={Echocardiographic abnormalities of the mitral valve associated with left sided heart diseases in the dog.}, volume={179}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0019881685&partnerID=MN8TOARS}, number={6}, journal={Journal of the American Veterinary Medical Association}, author={Pipers, F.S. and Bonagura, J.D. and Hamlin, R.L. and Kittleson, M.}, year={1981}, pages={580–586} }
 @article{bonagura_pipers_1981, title={Echocardiographic features of pericardial effusion in dogs.}, volume={179}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0019596731&partnerID=MN8TOARS}, number={1}, journal={Journal of the American Veterinary Medical Association}, author={Bonagura, J.D. and Pipers, F.S.}, year={1981}, pages={49–56} }
 @article{bonagura_1981, title={Electrical alternans associated with pericardial effusion in the dog.}, volume={178}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0019880514&partnerID=MN8TOARS}, number={6}, journal={Journal of the American Veterinary Medical Association}, author={Bonagura, J.D.}, year={1981}, pages={574–579} }
 @article{bonagura_1977, title={Feline Cardiovascular Emergencies}, volume={7}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0017492468&partnerID=MN8TOARS}, DOI={10.1016/s0091-0279(77)50037-8}, number={2}, journal={Veterinary Clinics of North America}, publisher={Elsevier BV}, author={Bonagura, John D.}, year={1977}, month={May}, pages={385–406} }