@article{gookin_holmes_clarke_stauffer_meredith_vandewege_torres-machado_friedenberg_seiler_mathews_et al._2024, title={Acquired dysfunction of CFTR underlies cystic fibrosis-like disease of the canine gallbladder}, volume={327}, ISSN={["1522-1547"]}, DOI={10.1152/ajpgi.00145.2024}, abstractNote={Cystic fibrosis transmembrane conductance regulatory protein (CFTR) genomic variants and expression of mRNA, protein, and electrogenic anion secretory activity of CFTR were characterized in dog gallbladder. Acquired inhibition of CFTR expression by gallbladder epithelium was identified as underpinning a naturally occurring muco-obstructive disease of the dog gallbladder that bears striking pathological similarity to animal models of cystic fibrosis.}, number={4}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY}, author={Gookin, Jody L. and Holmes, Jenny and Clarke, Lane L. and Stauffer, Stephen H. and Meredith, Bryanna and Vandewege, Michael W. and Torres-Machado, Nicole and Friedenberg, Steven G. and Seiler, Gabriela S. and Mathews, Kyle G. and et al.}, year={2024}, month={Oct}, pages={G513–G530} } @article{lairmore_byers_eaton_sykes_marks_meurs_2024, title={An imminent need for veterinary medical educators: are we facing a crisis?}, volume={262}, ISSN={["1943-569X"]}, DOI={10.2460/javma.24.04.0242}, abstractNote={Abstract A potential emerging shortage of veterinary medical educators requires the profession to acknowledge and understand the factors leading to this outcome. Expanding class sizes within existing schools and colleges of veterinary medicine and the expected expansion of new programs seeking AVMA–Council of Education accreditation have heightened the need to address an impending shortage of veterinary medical educators. A solution-oriented approach that accurately projects educator workforce needs and identifies factors contributing to the shortage requires effective collaboration across various partnering organizations to develop innovations in pedagogy and educational delivery methods. The veterinary profession must also identify and reduce disincentives that deter students and post-DVM trainees from pursuing careers in education. Finally, efforts at the state and federal level are critical to advocate for financial support and incentives for expansion of the veterinary medical educator workforce. Through these collective approaches and partnerships, the veterinary medical educator workforce can be strengthened to overcome obstacles for educating the next generation of veterinarians to meet societal needs.}, number={8}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Lairmore, Michael D. and Byers, Christopher and Eaton, Sarah and Sykes, Jane E. and Marks, Steven and Meurs, Kathryn M.}, year={2024}, month={Aug}, pages={1124–1128} } @article{ditzler_lashnits_meurs_maggi_yata_neupane_breitschwerdt_2024, title={The role of vector-borne pathogens and cardiac Striatin genotype on survival in boxer dogs with arrhythmogenic right ventricular cardiomyopathy}, volume={56}, ISSN={["1875-0834"]}, url={https://doi.org/10.1016/j.jvc.2024.09.002}, DOI={10.1016/j.jvc.2024.09.002}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Ditzler, B. and Lashnits, E. and Meurs, K. M. and Maggi, R. G. and Yata, M. and Neupane, P. and Breitschwerdt, E. B.}, year={2024}, month={Dec}, pages={84–96} } @article{reuter_defrancesco_robertson_meurs_2024, title={Clinical outcome of idiopathic juvenile ventricular arrhythmias in 25 dogs}, volume={51}, ISSN={["1875-0834"]}, url={https://doi.org/10.1016/j.jvc.2023.12.001}, DOI={10.1016/j.jvc.2023.12.001}, abstractNote={Juvenile ventricular arrhythmias in the absence of structural heart disease have been characterized in a small number of canine breeds with limited long-term follow up. The objective of this study was to describe the clinical outcome of dogs with JVA presenting to a university teaching hospital. 25 dogs, less than two years old with idiopathic ventricular arrhythmias were retrospectively identified via a medical record search. Young dogs with ventricular arrhythmias were excluded if they had structural heart disease, systemic illness, or an abnormal troponin (if performed). Electrocardiographic and Holter monitor data was evaluated for arrhythmia frequency and complexity at the time of diagnosis and over time. Long-term follow up was achieved through client and primary veterinarian contact. Breeds included German Shepherd (8), Boxer (4), Great Dane (3), mixed breed (2) and one each of the following: Anatolian Shepherd, French Bulldog, Golden Retriever, Great Pyrenees, Labrador Retriever, Shiloh Shepherd, Miniature Poodle and Siberian Husky. The average age at diagnosis was 7.9 months (range, 2–22 months). The overall median survival was 10.96 years (range, 1.75–15.66 years). There was an average reduction in the number of ventricular beats by 86.7 % per year (P value −0.0257) based on Holter data. In most cases, idiopathic juvenile ventricular arrhythmias had a favorable long-term prognosis with reduced ectopy over time in this case series. Juvenile ventricular arrhythmias remains a diagnosis of exclusion but can be considered in a broader range of dog breeds than previously described.}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Reuter, A. and DeFrancesco, T. C. and Robertson, J. B. and Meurs, K. M.}, year={2024}, month={Feb}, pages={188–194} } @article{kaplan_rivas_walker_grubb_farrell_fitzgerald_kennedy_pjauregui_crofton_pmclaughlin_et al._2023, title={Delayed-release rapamycin halts progression of left ventricular hypertrophy in subclinical feline hypertrophic results of the RAPACAT trial}, volume={261}, ISSN={["1943-569X"]}, url={https://publons.com/wos-op/publon/65523912/}, DOI={10.2460/javma.23.04.0187}, abstractNote={Abstract OBJECTIVE Feline hypertrophic cardiomyopathy (HCM) remains a disease with little therapeutic advancement. Rapamycin modulates the mTOR pathway, preventing and reversing cardiac hypertrophy in rodent disease models. Its use in human renal allograft patients is associated with reduced cardiac wall thickness. We sought to evaluate the effects of once-weekly delayed-release (DR) rapamycin over 6 months on echocardiographic, biochemical, and biomarker responses in cats with subclinical, nonobstructive HCM. ANIMALS 43 client-owned cats with subclinical HCM. METHODS Cats enrolled in this double-blinded, multicentered, randomized, and placebo-controlled clinical trial were allocated to low- or high-dose DR rapamycin or placebo. Cats underwent physical examination, quality-of-life assessment, blood pressure, hematology, biochemistry, total T4, urinalysis, N-terminal pro-B-type natriuretic peptide, and cardiac troponin I at baseline and days 60, 120, and 180. Fructosamine was analyzed at screening and day 180. Echocardiograms were performed at all time points excluding day 120. Outcome variables were compared using a repeated measures ANCOVA. RESULTS No demographic, echocardiographic, or clinicopathologic values were significantly different between study groups at baseline, confirming successful randomization. At day 180, the primary study outcome variable, maximum LV myocardial wall thickness at any location, was significantly lower in the low-dose DR rapamycin group compared to placebo (P = .01). Oral DR rapamycin was well tolerated with no significant differences in adverse events between groups. CLINICAL RELEVANCE Results demonstrate that DR rapamycin was well tolerated and may prevent or delay progressive LV hypertrophy in cats with subclinical HCM. Additional studies are warranted to confirm and further characterize these results. }, number={11}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Kaplan, Joanna L. and Rivas, Victor N. and Walker, Ashley L. and Grubb, Louise and Farrell, Aisling and Fitzgerald, Stuart and Kennedy, Susan and Pjauregui, Carina E. and Crofton, Amanda E. and Pmclaughlin, Chris and et al.}, year={2023}, month={Nov}, pages={1628–1637} } @article{adin_atkins_domenig_glahn_defrancesco_meurs_2023, title={Evaluation of Renin-Angiotensin-Aldosterone System Components and Enzymes in Systemically Hypertensive Cats Receiving Amlodipine}, volume={13}, ISSN={["2076-2615"]}, url={https://www.mdpi.com/2076-2615/13/22/3479}, DOI={10.3390/ani13223479}, abstractNote={Background: Chronic renin–angiotensin–aldosterone system (RAAS) activation is harmful. Amlodipine activates RAAS in humans and dogs, but contradictory data exist for systemically hypertensive (SHT) cats. Hypothesis: Cats with SHT and chronic kidney disease treated with amlodipine (SHT/CKD-A) are RAAS activated. Animals: Client-owned cats: unmedicated normotensive (NT) cats (n = 9); SHT/CKD-A cats (n = 5) with median systolic blood pressure of 170 mmHg (vs. 195 mmHg, pre-treatment), chronic kidney disease, and receiving no RAAS-suppressive therapy. Methods: Serum was frozen (−80 °C) until RAAS analysis via equilibrium analysis. The RAAS variables (reported as median (minimum–maximum)) were compared between groups, using Mann–Whitney U test. Results: Angiotensin 1, angiotensin 1,7, angiotensin III, and angiotensin 1,5, and angiotensin-converting enzyme (ACE)-2 activity were higher in SHT/CKD-A cats compared to NT cats, while ACE activity was lower in SHT/CKD-A cats compared to NT cats (p < 0.05 all). A marker for alternative RAAS influence (ALT-S) was significantly higher (69; 58–73 pmol/pmol) in SHT/CKD-A cats compared to NT cats (35; 14–63 pmol/pmol; p = 0.001). Aldosterone concentrations were significantly higher (393; 137–564 pmol/L) in SHT/CKD-A cats compared to NT cats (129; 28–206 pmol/L; p = 0.007). Conclusion and Clinical Importance: Circulating RAAS is activated in systemically hypertensive cats receiving amlodipine. Although this study did not parse out the individual contributions of SHT, chronic kidney disease, and amlodipine, the findings suggest that the use of concurrent RAAS-suppressant therapy, specifically aldosterone antagonism, in amlodipine-treated SHT cats with chronic kidney disease might be indicated.}, number={22}, journal={ANIMALS}, author={Adin, Darcy and Atkins, Clarke and Domenig, Oliver and Glahn, Catherine and Defrancesco, Teresa and Meurs, Kathryn}, year={2023}, month={Nov} } @article{walker_li_nguyen_jauregui_meurs_gagnon_stern_2023, title={Evaluation of autoantibodies to desmoglein-2 in dogs with and without cardiac disease}, volume={13}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/s41598-023-32081-x}, DOI={10.1038/s41598-023-32081-x}, abstractNote={AbstractAutoantibodies to desmoglein-2 have been associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) in people. ARVC is a common disease in the Boxer dog. The role of anti-desmoglein-2 antibodies in Boxers with ARVC and correlation with disease status or severity is unknown. This prospective study is the first to evaluate dogs of various breeds and cardiac disease state for anti-desmoglein-2 antibodies. The sera of 46 dogs (10 ARVC Boxers, 9 healthy Boxers, 10 Doberman Pinschers with dilated cardiomyopathy, 10 dogs with myxomatous mitral valve disease, and 7 healthy non-Boxer dogs) were assessed for antibody presence and concentration via Western blotting and densitometry. Anti-desmoglein-2 antibodies were detected in all dogs. Autoantibody expression did not differ between study groups and there was no correlation with age or body weight. In dogs with cardiac disease, there was weak correlation with left ventricular dilation (r = 0.423, p = 0.020) but not left atrial size (r = 0.160, p = 0.407). In ARVC Boxers there was strong correlation with the complexity of ventricular arrhythmias (r = 0.841, p = 0.007) but not total number of ectopic beats (r = 0.383, p = 0.313). Anti-desmoglein-2 antibodies were not disease specific in the studied population of dogs. Correlation with some measures of disease severity requires further study with larger populations.}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Walker, Ashley L. and Li, Ronald H. L. and Nguyen, Nghi and Jauregui, Carina E. and Meurs, Kathryn M. and Gagnon, Allison L. and Stern, Joshua A.}, year={2023}, month={Mar} } @article{agarwal_cote_o'sullivan_meurs_steiner_2023, title={Investigation of the cardiac effects of exercise testing on apparently healthy Boxer dogs}, volume={8}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.16830}, abstractNote={AbstractBackgroundHolter electrocardiographic monitoring is a cornerstone of diagnostic testing for arrhythmogenic cardiomyopathy (ACM) in Boxer dogs, but physical activity during monitoring is not controlled. In humans, exercise testing (ExT) can identify latent tachyarrhythmias associated with cardiomyopathy, and exercise increases serum cardiac troponin‐I concentrations ([hs‐cTnI]). These effects have not yet been investigated in Boxer dogs.Hypothesis/ObjectivesSubjecting Boxer dogs to brief, moderate‐intensity ExT can identify changes in Holter recordings and [hs‐cTnI] compared to baseline results.AnimalsThirty overtly healthy, client‐owned Boxer dogs.MethodsProspective interventional study. Dogs underwent baseline diagnostic testing including 24‐hour Holter monitoring and [hs‐cTnI], followed by brief ExT (accompanied, brisk stair‐climbing and ‐descending for <5 minutes).ResultsEleven dogs (37%) had >100 premature ventricular complexes (PVCs)/24 hours at baseline (3), ExT (3), or both (5). After ExT, these dogs had more PVCs/24 hours and greater increases in [hs‐cTnI] compared to those with ≤100 PVCs/24 hours. Dogs with the striatin mutation had more PVCs/24 hours and a greater increase in [hs‐cTnI] after ExT than did dogs without the striatin mutation.Conclusions and Clinical ImportanceExercise testing may improve the binary classification of Boxer dogs with or without ACM by increasing the number of PVCs and [hs‐cTnI] in affected dogs to a greater degree than in unaffected dogs. This effect also is associated with presence or absence of the striatin mutation. Exercise should be a controlled variable when screening Boxer dogs for ACM.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Agarwal, Deepmala and Cote, Etienne and O'Sullivan, Lynne and Meurs, Kathryn M. and Steiner, Jorg}, year={2023}, month={Aug} } @article{reimann_faisst_knold_meurs_stern_cremer_moller_ljungvall_haggstrom_olsen_2023, title={No impact of polymorphism in the phosphodiesterase 5A gene in Cavalier King Charles Spaniels on pimobendan-induced inhibition of platelet aggregation response}, volume={9}, ISSN={["1939-1676"]}, url={https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jvim.16871}, DOI={10.1111/jvim.16871}, abstractNote={AbstractBackgroundA variant in the canine phosphodiesterase (PDE) 5A gene (PDE5A:E90K) is associated with decreased concentrations of circulating cyclic guanosine monophosphate (cGMP) and response to PDE5 inhibitor treatment. Pimobendan is a PDE inhibitor recommended for medical treatment of certain stages of myxomatous mitral valve disease (MMVD) in dogs.HypothesisPDE5A:E90K polymorphism attenuates the inhibitory effect of pimobendan on in vitro platelet aggregation and increases basal platelet aggregation in Cavalier King Charles Spaniels (CKCS). Selected clinical variables (MMVD severity, sex, age, hematocrit, platelet count in platelet‐rich plasma [PRP], and echocardiographic left ventricular fractional shortening [LV FS]) will not show an association with results.AnimalsFifty‐two privately owned CKCS with no or preclinical MMVD.MethodsUsing blood samples, we prospectively assessed PDE5A genotype using Sanger sequencing and adenosine diphosphate‐induced platelet aggregation response (area under the curve [AUC], maximal aggregation [MaxA], and velocity [Vel]) with and without pimobendan using light transmission aggregometry. Dogs also underwent echocardiography.ResultsPimobendan inhibited platelet function as measured by AUC, MaxA, and Vel at a concentration of 10 μM (P < .0001) and Vel at 0.03 μM (P < .001). PDE5A:E90K polymorphism did not influence the inhibitory effect of pimobendan or basal platelet aggregation response.Conclusions and Clinical ImportanceThe PDE5A:E90K polymorphism did not influence in vitro basal platelet aggregation response or the inhibitory effect of pimobendan on platelet aggregation in CKCS. Dogs with the PDE5A:E90K polymorphism did not appear to have altered platelet function or response to pimobendan treatment.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Reimann, Maria J. and Faisst, Daniel N. and Knold, Mads and Meurs, Kathryn M. and Stern, Joshua A. and Cremer, Signe E. and Moller, Jacob E. and Ljungvall, Ingrid and Haggstrom, Jens and Olsen, Lisbeth H.}, year={2023}, month={Sep} } @article{mcmanamey_defrancesco_meurs_papich_2023, title={Pharmacokinetics of pimobendan after oral administration to dogs with myxomatous mitral valve disease}, volume={9}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.16891}, DOI={10.1111/jvim.16891}, abstractNote={AbstractBackgroundPimobendan is an important therapy for dogs with myxomatous mitral valve disease (MMVD). The pharmacokinetics are reported in healthy dogs but not in dogs with heart disease.Hypothesis/ObjectivesTo determine if dog characteristics such as age, breed, body condition score, ACVIM stage of heart disease or biochemical laboratory value alter the pharmacokinetics of orally administered pimobendan and its metabolite in a cohort of dogs with naturally occurring MMVD.AnimalsFifty‐seven client‐owned dogs with MMVD ACVIM Stage B2, C, or D and administered pimobendan to steady state blood concentrations.MethodsProspective, observational study. Samples were collected using a sparse‐sampling protocol at specific intervals after administration of pimobendan. Plasma pimobendan and the active metabolite (O‐desmethyl‐pimobendan, ODMP) concentrations were determined via high‐pressure liquid chromatography and fluorescence detection. Data was analyzed via a population pharmacokinetic approach and nonlinear mixed effects modeling (NLME). Numerous covariates were examined in the NLME model.ResultsThe absorption and elimination half‐lives (t1/2) were approximately 1.4 and 1 hour for pimobendan and 1.4 and 1.3 hours for ODMP, respectively. Pharmacokinetic parameters were highly variable, especially the values for pimobendan absorption and elimination rate, and absorption rate of ODMP with coefficients of variation of 147.84%, 64.51% and 64.49%, respectively. No covariate evaluated was a significant source of variability.Conclusions and Clinical ImportanceThe pharmacokinetic parameters were highly variable among this group of dogs with MMVD. The variability was not associated with the dog's age, body weight or condition score, stage of heart disease, dose, serum creatinine, or alkaline phosphatase.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={McManamey, Anna K. and DeFrancesco, Teresa C. and Meurs, Kathryn M. and Papich, Mark G.}, year={2023}, month={Sep} } @article{brethel_locker_girens_rivera_meurs_adin_2023, title={The effect of taurine supplementation on the renin-angiotensin-aldosterone system of dogs with congestive heart failure}, volume={13}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-023-37978-1}, abstractNote={AbstractThe role of taurine in the treatment of congestive heart failure (CHF) in dogs without systemic deficiency is unexplored. Taurine might have beneficial cardiac effects aside from deficit replacement. We hypothesized that oral taurine supplementation administered to dogs with naturally-occurring CHF would suppress the renin-angiotensin aldosterone system (RAAS). Oral taurine was administered to 14 dogs with stable CHF. Serum biochemical variables, blood taurine concentrations, and comprehensive analysis of RAAS variables were compared before and 2 weeks after taurine supplementation added to background furosemide and pimobendan therapy for CHF. Whole blood taurine concentrations increased after supplementation (median 408 nMol/mL, range 248–608 before and median 493 nMol/mL, range 396–690 after; P = .006). Aldosterone to angiotensin II ratio (AA2) was significantly decreased after taurine supplementation (median 1.00, range 0.03–7.05 before and median 0.65, range 0.01–3.63 after; P = .009), but no other RAAS components significantly differed between timepoints. A subset of dogs showed marked decreases in RAAS metabolites after supplementation and these dogs were more likely to have been recently hospitalized for CHF treatment than dogs that did not show marked decreases in classical RAAS metabolites. Overall, taurine only lowered AA2 in this group of dogs, however, response heterogeneity was noted, with some dogs showing RAAS suppression.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Brethel, Sara and Locker, Seth and Girens, Renee and Rivera, Paulo and Meurs, Kathryn and Adin, Darcy}, year={2023}, month={Jul} } @article{woelfel_meurs_friedenberg_debruyne_olby_2022, title={A novel mutation of the CLCN1 gene in a cat with myotonia congenita: Diagnosis and treatment}, volume={7}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.16471}, DOI={10.1111/jvim.16471}, abstractNote={AbstractCase DescriptionA 10‐month‐old castrated male domestic longhair cat was evaluated for increasing frequency of episodic limb rigidity.Clinical FindingsThe cat presented for falling over and lying recumbent with its limbs in extension for several seconds when startled or excited. Upon examination, the cat had hypertrophied musculature, episodes of facial spasm, and a short‐strided, stiff gait.DiagnosticsElectromyography (EMG) identified spontaneous discharges that waxed and waned in amplitude and frequency, consistent with myotonic discharges. A high impact 8‐base pair (bp) deletion across the end of exon 3 and intron 3 of the chloride voltage‐gated channel 1 (CLCN1) gene was identified using whole genome sequencing.Treatment and OutcomePhenytoin treatment was initiated at 3 mg/kg po q24 h and resulted in long‐term improvement.Clinical RelevanceThis novel mutation within the CLCN1 gene is a cause of myotonia congenita in cats and we report for the first time its successful treatment.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Woelfel, Christian and Meurs, Kathryn and Friedenberg, Steven and DeBruyne, Nicole and Olby, Natasha J.}, year={2022}, month={Jul} } @article{meurs_2022, title={Hands-on learning: from at-risk wolves to teeming Galapagos}, volume={260}, ISSN={["1943-569X"]}, DOI={10.2460/javma.22.05.0216}, abstractNote={N C State is unsurpassed in the variety of ways we offer rare hands-on experiences for our veterinary students}, number={10}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Meurs, Kathryn}, year={2022}, month={Jul}, pages={1140–1140} } @article{meurs_montgomery_friedenberg_williams_gilger_2021, title={A defect in the NOG gene increases susceptibility to spontaneous superficial chronic corneal epithelial defects (SCCED) in boxer dogs}, volume={17}, ISSN={1746-6148}, url={http://dx.doi.org/10.1186/s12917-021-02955-1}, DOI={10.1186/s12917-021-02955-1}, abstractNote={Abstract Background Superficial chronic corneal epithelial defects (SCCEDs) are spontaneous corneal defects in dogs that share many clinical and pathologic characteristics to recurrent corneal erosions (RCE) in humans. Boxer dogs are predisposed to SCCEDs, therefore a search for a genetic defect was performed to explain this susceptibility. DNA was extracted from blood collected from Boxer dogs with and without SCCEDs followed by whole genome sequencing (WGS). RNA sequencing of corneal tissue and immunostaining of corneal sections from affected SCCED Boxer dogs with a deletion in the NOG gene and affected non-Boxer dogs without the deletion were performed. Results A 30 base pair deletion at a splice site in Noggin (NOG) (Chr 9:31453999) was identified by WGS and was significantly associated (P < 0.0001) with Boxer SCCEDs compared to unaffected non-Boxer dogs. NOG, BMP4, MMP13, and NCAM1 all had significant fold reductions in expression and SHH was significantly increased in Boxers with the NOG deletion as identified by RNA-Seq. Corneal IHC from NOG deletion dogs with SCCEDs had lower NOG and significantly higher scores of BMP2. Conclusions Many Boxer dogs with SCCED have a genetic defect in NOG. NOG is a constitutive protein in the cornea which is a potent inhibitor of BMP, which likely regulate limbal epithelial progenitor cells (LEPC). Dysregulation of LEPC may play a role in the pathogenesis of RCE. }, number={1}, journal={BMC Veterinary Research}, publisher={Springer Science and Business Media LLC}, author={Meurs, Kathryn M. and Montgomery, Keith and Friedenberg, Steven G. and Williams, Brian and Gilger, Brian C.}, year={2021}, month={Jul} } @article{meurs_williams_deprospero_friedenberg_malarkey_ezzell_keene_adin_defrancesco_tou_2021, title={A deleterious mutation in the ALMS1 gene in a naturally occurring model of hypertrophic cardiomyopathy in the Sphynx cat}, volume={16}, ISSN={["1750-1172"]}, DOI={10.1186/s13023-021-01740-5}, abstractNote={Abstract Background Familial hypertrophic cardiomyopathy is a common inherited cardiovascular disorder in people. Many causal mutations have been identified, but about 40% of cases do not have a known causative mutation. Mutations in the ALMS1 gene are associated with the development of Alstrom syndrome, a multisystem familial disease that can include cardiomyopathy (dilated, restrictive). Hypertrophic cardiomyopathy has not been described. The ALMS1 gene is a large gene that encodes for a ubiquitously expressed protein. The function of the protein is not well understood although it is believed to be associated with energy metabolism and homeostasis, cell differentiation and cell cycle control. The ALMS1 protein has also been shown to be involved in the regulation of cell cycle proliferation in perinatal cardiomyocytes. Although cardiomyocyte cell division and replication in mammals generally declines soon after birth, inhibition of ALMS1 expression in mice lead to increased cardiomyocyte proliferation, and deficiency of Alstrom protein has been suggested to impair post-natal cardiomyocyte cell cycle arrest. Here we describe the association of familial hypertrophic cardiomyopathy in Sphynx cats with a novel ALMS1 mutation. Results A G/C variant was identified in exon 12 (human exon 13) of the ALMS1 gene in affected cats and was positively associated with the presence of hypertrophic cardiomyopathy in the feline population (p < 0.0001). The variant was predicted to change a highly conserved nonpolar Glycine to a positively charged Arginine. This was predicted to be a deleterious change by three in silico programs. Protein prediction programs indicated that the variant changed the protein structure in this region from a coil to a helix. Light microscopy findings included myofiber disarray with interstitial fibrosis with significantly more nuclear proliferative activity in the affected cats than controls (p < 0.0001). Conclusion This study demonstrates a novel form of cardiomyopathy associated with ALMS1 in the cat. Familial hypertrophic cardiomyopathy is a disease of genetic heterogeneity; many of the known causative genes encoding for sarcomeric proteins. Our findings suggest that variants in genes involved with cardiac development and cell regulation, like the ALMS1 gene, may deserve further consideration for association with familial hypertrophic cardiomyopathy. }, number={1}, journal={ORPHANET JOURNAL OF RARE DISEASES}, author={Meurs, Kathryn M. and Williams, Brian G. and DeProspero, Dylan and Friedenberg, Steven G. and Malarkey, David E. and Ezzell, J. Ashley and Keene, Bruce W. and Adin, Darcy B. and DeFrancesco, Teresa C. and Tou, Sandra}, year={2021}, month={Feb} } @article{hedgespeth_birkenheuer_friedenberg_olby_meurs_2021, title={A novel missense mutation of the NAT10 gene in a juvenile Schnauzer dog with chronic respiratory tract infections}, volume={35}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.16100}, DOI={10.1111/jvim.16100}, abstractNote={AbstractAn 18‐month‐old intact male Schnauzer dog was evaluated for chronic, lifelong respiratory tract infections that were unresponsive to administration of a variety of antibiotics and corticosteroids. The dog developed persistent vomiting and diarrhea around 1 year of age that was minimally responsive to diet change, antibiotics, and corticosteroids. Despite supportive care, the dog was ultimately euthanized at 20 months of age due to persistent respiratory and gastrointestinal disease. Whole genome sequencing discovered a deleterious missense A/C mutation within the NAT10 gene, a gene essential for microtubule acetylation, appropriate ciliary development, and cytokinesis. Pipeline analysis of the genomes of 579 dogs from 55 breeds did not detect this mutation. Though never described in veterinary medicine, NAT10 mutation occurs in humans with ciliary aplasia, suggesting a pathophysiological mechanism for this dog and highlighting an associated mutation or possible novel genetic cause of chronic respiratory infections in dogs.}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Hedgespeth, Barry A. and Birkenheuer, Adam J. and Friedenberg, Steven G. and Olby, Natasha J. and Meurs, Kathryn M.}, year={2021}, month={May}, pages={1542–1546} } @misc{shen_estrada_meurs_sleeper_vulpe_martyniuk_pacak_2022, title={A review of the underlying genetics and emerging therapies for canine cardiomyopathies}, volume={40}, ISSN={["1875-0834"]}, DOI={10.1016/j.jvc.2021.05.003}, abstractNote={Cardiomyopathies such as dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are common in large breed dogs and carry an overall poor prognosis. Research shows that these diseases have strong breed predilections, and selective breeding has historically been recommended to reduce the disease prevalence in affected breeds. Treatment of these diseases is typically palliative and aimed at slowing disease progression and managing clinical signs of heart failure as they develop. The discovery of specific genetic mutations underlying cardiomyopathies, such as the striatin mutation in Boxer arrhythmogenic right ventricular cardiomyopathy and the pyruvate dehydrogenase kinase 4 and titin mutations in Doberman Pinschers, has strengthened our ability to screen and selectively breed individuals in an attempt to produce unaffected offspring. The discovery of these disease-linked mutations has also opened avenues for the development of gene therapies, including gene transfer and genome-editing approaches. This review article discusses the known genetics of cardiomyopathies in dogs, reviews existing gene therapy strategies and the status of their development in canines, and discusses ongoing challenges in the clinical translation of these technologies for treating heart disease. While challenges remain in using these emerging technologies, the exponential growth of the gene therapy field holds great promise for future clinical applications.}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Shen, L. and Estrada, A. H. and Meurs, K. M. and Sleeper, M. and Vulpe, C. and Martyniuk, C. J. and Pacak, C. A.}, year={2022}, month={Apr}, pages={2–14} } @article{k. o'donnell_adin_atkins_defrancesco_keene_tou_meurs_2021, title={Absence of known feline MYH7 and MYBPC3 variants in a diverse cohort of cats with hypertrophic cardiomyopathy}, volume={52}, ISSN={["1365-2052"]}, DOI={10.1111/age.13074}, abstractNote={SummaryHypertrophic cardiomyopathy (HCM) is the most common cause of heart disease in the domestic cat with a genetic predisposition in a few breeds. In the Maine Coon and Ragdoll breeds, two variants associated with the HCM phenotype have been identified in the cardiac myosin binding protein C gene (MYBPC3; p.Ala31Pro and p.Arg820Trp respectively), and a single variant has been identified in the myosin heavy chain gene (MYH7; p.Glu1883Lys) in one domestic cat with HCM. It is not known if these variants influence the development of HCM in other cohorts of the feline population. The objective of this study was to evaluate the presence of the known MYBPC3 and MYH7 variants in a population of cats with HCM. DNA was isolated from samples collected from non‐Ragdoll and non‐Maine Coon domestic cats diagnosed with HCM through the North Carolina State University College of Veterinary Medicine and genotyped for the three variants. One‐hundred and three DNA samples from cats with HCM were evaluated from domestic shorthair, domestic longhair and purebred cats. All samples were wt for the MYBPC3 and MYH7 variants. Although this study was limited by its inclusion of cats from one tertiary hospital, the lack of these MYBPC3 and MYH7 variants in this feline HCM population indicates that the clinical utility of genetic testing for these variants may be isolated to the two cat breeds in which these variants have been identified. Further studies to identify the causative variants for the feline HCM population are warranted.}, number={4}, journal={ANIMAL GENETICS}, author={K. O'Donnell and Adin, D. and Atkins, C. E. and DeFrancesco, T. and Keene, B. W. and Tou, S. and Meurs, K. M.}, year={2021}, month={Aug}, pages={542–544} } @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={{"Label"=>"INTRODUCTION", "NlmCategory"=>"BACKGROUND"} 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. {"Label"=>"HYPOTHESIS", "NlmCategory"=>"OBJECTIVE"} Prior GF (pGF) diet influences reverse cardiac remodeling and clinical outcomes in dogs with DCM and congestive heart failure (CHF). {"Label"=>"ANIMALS AND METHODS", "NlmCategory"=>"METHODS"} 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. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} 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. {"Label"=>"CONCLUSIONS", "NlmCategory"=>"CONCLUSIONS"} 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{herrmann_linder_meurs_friedenberg_cullen_olby_bizikova_2021, title={Canine junctional epidermolysis bullosa due to a novel mutation in LAMA3 with severe upper respiratory involvement}, volume={32}, ISSN={["1365-3164"]}, url={https://doi.org/10.1111/vde.12972}, DOI={10.1111/vde.12972}, abstractNote={BackgroundJunctional epidermolysis bullosa (JEB) is a group of congenital blistering skin diseases characterized by clefting through the lamina lucida of the basement membrane zone.ObjectivesTo characterize the clinical and morphological features of a congenital mechanobullous disease in a litter of puppies with severe upper respiratory involvement, and to identify an associated genetic variant.AnimalsFive of eight puppies in an Australian cattle dog cross‐bred litter showed signs of skin fragility. Three were stillborn and one died at one month of age. The two surviving puppies were presented with blistering skin disease and severe respiratory distress. Additionally, one unaffected sibling was examined and blood was obtained for genetic testing.Methods and materialsPost‐mortem examination, histopathological evaluation and electron microscopy were performed. Whole genome sequencing (WGS) of one affected puppy was compared to a database of 522 dogs of 55 different breeds for variant analysis. Sanger sequencing of one additional affected and one unaffected sibling confirmed the variant.ResultsClinically, severe mucocutaneous ulcers occurred in frictional areas with claw sloughing. Histopathological results revealed subepidermal clefts and electron microscopy confirmed the split in the lamina lucida. Post‐mortem examination documented extensive pharyngeal and laryngeal lesions with granulation tissue and fibrinous exudate obscuring the airway. Moderate tracheal hypoplasia contributed. The WGS revealed a novel missense variant in the laminin α3‐chain XP_537297.2p(Asp2867Val), with an autosomal recessive mode of inheritance.Conclusions and clinical relevanceA novel variant in LAMA3 caused a generalized and severe phenotype of JEB with an unique clinical presentation of upper airway obstruction.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={Herrmann, Ina and Linder, Keith E. and Meurs, Kathryn M. and Friedenberg, Steven G. and Cullen, Jonah and Olby, Natasha and Bizikova, Petra}, year={2021}, month={Aug}, pages={379-+} } @article{deprospero_kerry a. o'donnell_defrancesco_keene_tou_adin_atkins_meurs_2021, title={Myxomatous mitral valve disease in Miniature Schnauzers and Yorkshire Terriers: 134 cases (2007-2016)}, volume={259}, ISSN={["1943-569X"]}, DOI={10.2460/javma.20.05.0291}, abstractNote={Abstract OBJECTIVE To characterize features of myxomatous mitral valve disease (MMVD) in Miniature Schnauzers and Yorkshire Terriers. ANIMALS 69 Miniature Schnauzers and 65 Yorkshire Terriers, each with MMVD. PROCEDURES Medical record data for each dog were collected; the study period was January 2007 through December 2016. If available, radiographic data were evaluated, and a vertebral heart scale score was assigned for each dog. Statistical analysis was performed with Student t and Fisher exact tests. RESULTS Compared with Yorkshire Terriers, the prevalence of MMVD was significantly higher in Miniature Schnauzers and affected dogs were significantly younger at the time of diagnosis. Miniature Schnauzers were significantly more likely to have mitral valve prolapse and syncope, compared with Yorkshire Terriers. Yorkshire Terriers were significantly more likely to have coughing and have had previous or current treatment with cardiac medications, compared with Miniature Schnauzers. There was no statistical difference between breeds with regard to abnormally high vertebral heart scale scores or radiographic evidence of congestive heart failure. CONCLUSIONS AND CLINICAL RELEVANCE With regard to MMVD, features of the disease among Miniature Schnauzers and Yorkshire Terriers were similar, but there were also a few discernable differences between these 2 breeds and from historical findings for dogs with MMVD of other breeds. Clinical signs at the time of diagnosis differed between the 2 breeds, which may have reflected concurrent breed-specific conditions (sick sinus syndrome or airway disease [eg, tracheal collapse]). Future work should include prospective studies to provide additional information regarding the natural progression of MMVD in these dog breeds. }, number={12}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={DeProspero, Dylan J. and Kerry A. O'Donnell and DeFrancesco, Teresa C. and Keene, Bruce W. and Tou, Sandra P. and Adin, Darcy B. and Atkins, Clarke E. and Meurs, Kathryn M.}, year={2021}, month={Dec}, pages={1428–1432} } @article{reimann_fredholm_cremer_christiansen_meurs_moller_haggstrom_lykkesfeldt_olsen_2021, title={Polymorphisms in the serotonin transporter gene and circulating concentrations of neurotransmitters in Cavalier King Charles Spaniels with myxomatous mitral valve disease}, volume={10}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.16277}, abstractNote={AbstractBackgroundThe neurotransmitter serotonin (5‐HT) affects valvular degeneration and dogs with myxomatous mitral valve disease (MMVD) exhibit alterations in 5‐HT signaling. In Maltese dogs, 3 single nucleotide polymorphisms (SNPs) in the 5‐HT transporter (SERT) gene are suggested to associate with MMVD.Hypothesis/ObjectivesDetermine the association of SERT polymorphisms on MMVD severity and serum 5‐HT concentration in Cavalier King Charles Spaniels (CKCS). Additionally, investigate the association between selected clinical and hematologic variables and serum 5‐HT and assess the correlation between HPLC and ELISA measurements of serum 5‐HT.AnimalsSeventy‐one CKCS (42 females and 29 males; 7.8 [4.7;9.9] years (median [Q1;Q3])) in different MMVD stages.MethodsThis prospective study used TaqMan genotyping assays to assess SERT gene polymorphisms. Neurotransmitter concentrations were assessed by HPLC and ELISA.ResultsTaqMan analyses identified none of the selected SERT polymorphisms in any of the CKCS examined. Serum 5‐HT was associated with platelet count (P < .001) but not MMVD severity, age or medical therapy and did not correlate with serum concentration of the 5‐HT metabolite, 5‐hydroxyindoleacetic acid. The ELISA serum 5‐HT correlated with HPLC measurements (ρ = .87; P < .0001) but was lower (mean difference = −22 ng/mL; P = .02) independent of serum 5‐HT concentration (P = .2).Conclusions and Clinical ImportanceSelected SERT SNPs associated with MMVD in Maltese dogs were not found in CKCS and only platelet count influenced serum 5‐HT concentration. These SNPs are unlikely to be associated with MMVD pathophysiology or serum 5‐HT concentration in CKCS. HPLC and ELISA serum 5‐HT demonstrated good correlation but ELISA systematically underestimated 5‐HT.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Reimann, Maria J. and Fredholm, Merete and Cremer, Signe E. and Christiansen, Liselotte B. and Meurs, Kathryn M. and Moller, Jacob E. and Haggstrom, Jens and Lykkesfeldt, Jens and Olsen, Lisbeth H.}, year={2021}, month={Oct} } @article{williams_friedenberg_keene_tou_defrancesco_meurs_2021, title={Use of whole genome analysis to identify shared genomic variants across breeds in canine mitral valve disease}, volume={6}, ISSN={["1432-1203"]}, DOI={10.1007/s00439-021-02297-w}, abstractNote={Familial mitral valve prolapse in human beings has been associated with several genetic variants; however, in most cases, a known variant has not been identified. Dogs also have a naturally occurring form of familial mitral valve disease (MMVD) with similarities to the human disease. A shared genetic background and clinical phenotype of this disease in some dog breeds has indicated that the disease may share a common genetic cause. We evaluated DNA from 50 affected dogs from five different dog breeds in a whole genome sequencing approach to identify shared variants across and within breeds that could be associated with MMVD. No single causative genetic mutation was found from the 50 dogs with MMVD. Ten variants were identified in 37/50 dogs around and within the MED13L gene. These variants were no longer associated with MMVD when evaluated with a larger cohort including both affected and unaffected dogs. No high/moderate impact variants were identified in 10/10 miniature poodles, one was identified in 10/10 Yorkshire Terriers and 10/10 dachshunds, respectively, 14 were identified in 10/10 Miniature schnauzers, and 19 in 10/10 CKCS. Only one of these could be associated with the cardiac valve (Chr12:36801705, COL12A1; CKCS) but when evaluated in an additional 100 affected CKCS the variant was only identified in 84/100 affected dogs, perhaps indicating genetic heterogeneity in this disease. Our findings indicate that development of MMVD in the dog may be related to a combination of genetic and environmental factors that impact specific molecular pathways rather than a single shared genetic variant across or within breeds.}, journal={HUMAN GENETICS}, author={Williams, Brian and Friedenberg, Steven G. and Keene, Bruce W. and Tou, Sandy P. and DeFrancesco, Teresa C. and Meurs, Kathryn M.}, year={2021}, month={Jun} } @article{olby_friedenberg_meurs_deprospero_guevar_lau_yost_guo_shelton_2020, title={A mutation in MTM1 causes X-Linked myotubular myopathy in Boykin spaniels}, volume={30}, ISSN={0960-8966}, url={http://dx.doi.org/10.1016/j.nmd.2020.02.021}, DOI={10.1016/j.nmd.2020.02.021}, abstractNote={The purpose of this study was to report the findings of clinical and genetic evaluation of a 3-month old male Boykin spaniel (the proband) that presented with progressive weakness. The puppy underwent a physical and neurological examination, serum biochemistry and complete blood cell count, electrophysiological testing, muscle biopsy and whole genome sequencing. Clinical evaluation revealed generalized neuromuscular weakness with tetraparesis and difficulty holding the head up and a dropped jaw. There was diffuse spontaneous activity on electromyography, most severe in the cervical musculature. Nerve conduction studies were normal, the findings were interpreted as consistent with a myopathy. Skeletal muscle was grossly abnormal on biopsy and there were necklace fibers and abnormal triad structure localization on histopathology, consistent with myotubular myopathy. Whole genome sequencing revealed a premature stop codon in exon 13 of MTM1 (ChrX: 118,903,496 C > T, c.1467C>T, p.Arg512X). The puppy was humanely euthanized at 5 months of age. The puppy's dam was heterozygous for the variant, and 3 male puppies from a subsequent litter all of which died by 2 weeks of age were hemizygous for the variant. This naturally occurring mutation in Boykin spaniels causes a severe form of X-linked myotubular myopathy, comparable to the human counterpart.}, number={5}, journal={Neuromuscular Disorders}, publisher={Elsevier BV}, author={Olby, Natasha J. and Friedenberg, Steven and Meurs, Kathryn and DeProspero, Dylan and Guevar, Julien and Lau, Jeanie and Yost, Oriana and Guo, Ling T. and Shelton, G. Diane}, year={2020}, month={Mar}, pages={353–359} } @article{adin_atkins_domenig_defrancesco_keene_tou_stern_meurs_2020, title={Renin-angiotensin aldosterone profile before and after angiotensin-converting enzyme-inhibitor administration in dogs with angiotensin-converting enzyme gene polymorphism}, volume={34}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.15746}, DOI={10.1111/jvim.15746}, abstractNote={AbstractBackgroundAn angiotensin‐converting enzyme (ACE) gene polymorphism occurs in dogs; however, functional importance is not well studied.HypothesisWe hypothesized that dogs with the polymorphism would show alternative renin‐angiotensin aldosterone system (RAAS) pathway activation and classical RAAS pathway suppression before and after ACE‐inhibitor administration, as compared to dogs without the polymorphism that would show this pattern only after ACE‐inhibitor administration.AnimalsTwenty‐one dogs with mitral valve disease that were genotyped for the ACE gene polymorphism.MethodsThis retrospective study utilized stored samples from 8 ACE gene polymorphism‐negative (PN) dogs and 13 ACE gene polymorphism‐positive (PP) dogs before and after enalapril administration. Equilibrium analysis was performed to evaluate serum RAAS metabolites and enzyme activities. Results were compared before and after enalapril, and between groups.ResultsThe classical RAAS pathway was suppressed and the alternative RAAS pathway was enhanced for both genotypes after administration of enalapril, with no differences before enalapril administration. Aldosterone breakthrough occurred in both PN (38%) and PP (54%) dogs despite angiotensin II suppression. Aldosterone was significantly higher (P = .02) in ACE gene PP dogs (median, 92.17 pM; IQR, 21.85‐184.70) compared to ACE gene PN dogs (median, 15.91 pM; IQR, <15.00‐33.92) after enalapril.Conclusions and Clinical ImportanceThe ACE gene polymorphism did not alter baseline RAAS activity. Aldosterone breatkthrough in some dogs suggests nonangiotensin mediated aldosterone production that might be negatively influenced by genotype. These results support the use of aldosterone receptor antagonists with ACE‐inhibitors when RAAS inhibition is indicated for dogs, especially those positive for the ACE gene polymorphism.}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Adin, Darcy and Atkins, Clarke and Domenig, Oliver and DeFrancesco, Teresa and Keene, Bruce and Tou, Sandra and Stern, Joshua A. and Meurs, Kathryn M.}, year={2020}, month={Mar}, pages={600–606} } @article{meurs_friedenberg_olby_condit_weidman_rosenthal_shelton_2019, title={A QIL1 Variant Associated with Ventricular Arrhythmias and Sudden Cardiac Death in the Juvenile Rhodesian Ridgeback Dog}, volume={10}, ISSN={2073-4425}, url={http://dx.doi.org/10.3390/genes10020168}, DOI={10.3390/genes10020168}, abstractNote={The QIl1 gene produces a component of the Mitochondrial Contact Site and Cristae Organizing System that forms and stabilizes mitochondrial cristae junctions and is important in cellular energy production. We previously reported a family of Rhodesian Ridgebacks with cardiac arrhythmias and sudden cardiac death. Here, we performed whole genome sequencing on a trio from the family. Variant calling was performed using a standardized bioinformatics approach. Variants were filtered against variants from 247 dogs of 43 different breeds. High impact variants were validated against additional affected and unaffected dogs. A single missense G/A variant in the QIL1 gene was associated with the cardiac arrhythmia (p < 0.0001). The variant was predicted to change the amino acid from conserved Glycine to Serine and to be deleterious. Ultrastructural analysis of the biceps femoris muscle from an affected dog revealed hyperplastic mitochondria, cristae rearrangement, electron dense inclusions and lipid bodies. We identified a variant in the Q1l1 gene resulting in a mitochondrial cardiomyopathy characterized by cristae abnormalities and cardiac arrhythmias in a canine model. This natural animal model of mitochondrial cardiomyopathy provides a large animal model with which to study the development and progression of disease as well as genotypic phenotypic relationships.}, number={2}, journal={Genes}, publisher={MDPI AG}, author={Meurs, Kathryn and Friedenberg, Steven and Olby, Natasha and Condit, Julia and Weidman, Jess and Rosenthal, Steve and Shelton, G.}, year={2019}, month={Feb}, pages={168} } @article{meurs_friedenberg_kolb_saripalli_tonino_woodruff_olby_keene_adin_yost_et al._2019, title={A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death}, volume={138}, ISSN={0340-6717 1432-1203}, url={http://dx.doi.org/10.1007/s00439-019-01973-2}, DOI={10.1007/s00439-019-01973-2}, abstractNote={The dog provides a large animal model of familial dilated cardiomyopathy for the study of important aspects of this common familial cardiovascular disease. We have previously demonstrated a form of canine dilated cardiomyopathy in the Doberman pinscher breed that is inherited as an autosomal dominant trait and is associated with a splice site variant in the pyruvate dehydrogenase kinase 4 (PDK4) gene, however, genetic heterogeneity exists in this species as well and not all affected dogs have the PDK4 variant. Whole genome sequencing of a family of Doberman pinchers with dilated cardiomyopathy and sudden cardiac death without the PDK4 variant was performed. A pathologic missense variant in the titin gene located in an immunoglobulin-like domain in the I-band spanning region of the molecule was identified and was highly associated with the disease (p < 0.0001). We demonstrate here the identification of a variant in the titin gene highly associated with the disease in this spontaneous canine model of dilated cardiomyopathy. This large animal model of familial dilated cardiomyopathy shares many similarities with the human disease including mode of inheritance, clinical presentation, genetic heterogeneity and a pathologic variant in the titin gene. The dog is an excellent model to improve our understanding of the genotypic phenotypic relationships, penetrance, expression and the pathophysiology of variants in the titin gene.}, number={5}, journal={Human Genetics}, publisher={Springer Science and Business Media LLC}, author={Meurs, Kathryn M. and Friedenberg, Steven G. and Kolb, Justin and Saripalli, Chandra and Tonino, Paola and Woodruff, Kathleen and Olby, Natasha J. and Keene, Bruce W. and Adin, Darcy B. and Yost, Oriana L. and et al.}, year={2019}, month={Feb}, pages={515–524} } @article{gandolfi_alhaddad_abdi_bach_creighton_davis_decker_dodman_ginns_grahn_et al._2019, title={Applications and efficiencies of the first cat 63 K DNA array (vol 8, 7024, 2018)}, volume={9}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-018-38073-6}, abstractNote={A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.}, journal={SCIENTIFIC REPORTS}, author={Gandolfi, Barbara and Alhaddad, Hasan and Abdi, Mona and Bach, Leslie H. and Creighton, Erica K. and Davis, Brian W. and Decker, Jared E. and Dodman, Nicholas H. and Ginns, Edward I. and Grahn, Jennifer C. and et al.}, year={2019}, month={Mar} } @article{agler_friedenberg_olivry_meurs_olby_2019, title={Genome-wide association analysis in West Highland White Terriers with atopic dermatitis}, volume={209}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/j.vetimm.2019.01.004}, DOI={10.1016/j.vetimm.2019.01.004}, abstractNote={{"Label"=>"BACKGROUND", "NlmCategory"=>"BACKGROUND"} Atopic dermatitis (AD) is a common disease of dogs and humans. In both species, the interplay of genetic and environmental factors affect disease expression. In dogs with AD, differences in the breed studied and in their geographical origin have led to heterogeneity in genetic association and while different loci have been identified, a causative genetic mutation has not. We hypothesized that AD could be mapped in a large cohort of rigorously phenotyped, geographically restricted West Highland White Terriers (WHWT), a breed with a high prevalence of the disease. {"Label"=>"OBJECTIVES", "NlmCategory"=>"OBJECTIVE"} A) Collect phenotypes and DNA from a large cohort of WHWT born in the USA. B) Perform a genome-wide association study (GWAS) for AD in these dogs to identify associated regions and genes of interest. C) Sequence genes of interest to identify pathologic variants. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} We collected DNA from 96 WHWT with AD and 87 controls from the same breed. DNA was isolated and dogs were genotyped using the Illumina CanineHD BeadChip. A GWAS was performed using EMMAX and associated regions were examined for genes of interest. Genes with possible relevance to AD were examined more closely in two affected and two normal WHWT using next-generation sequencing. Variants in these genes that were unique to the two affected WHWT were compared to a database of variants derived from whole genome sequencing of 200 non-WHWT dogs across 33 additional breeds. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} The GWAS identified a 2.7 Mb genomic region on CFA3 that included 37 genes. There was a missense variant in the F2R gene in both affected dogs but this variant was also found in 35 dogs in 9 breeds in the database of whole genome sequences for whom the phenotype regarding atopic dermatitis was unknown. {"Label"=>"CONCLUSIONS", "NlmCategory"=>"CONCLUSIONS"} Atopic dermatitis in WHWT is associated with a region on CFA3 that contains several candidate genes. Of these, a homozygous variant in the F2R gene present in multiple breeds that also suffer from AD warrants further evaluation.}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Agler, Cary S. and Friedenberg, Steven and Olivry, Thierry and Meurs, Kate M. and Olby, Natasha J.}, year={2019}, month={Mar}, pages={1–6} } @article{williams_friedenberg_meurs_2019, title={INVOLVEMENT OF SEROTONIN IN A CANINE MODEL OF MITRAL VALVE PROLAPSE: A COMPLEX GENETIC APPROACH}, volume={73}, ISSN={0735-1097}, url={http://dx.doi.org/10.1016/S0735-1097(19)31564-5}, DOI={10.1016/S0735-1097(19)31564-5}, abstractNote={In humans, mitral valve prolapse (MVP) is a common heritable condition. Dogs serve as a spontaneous animal model of familial MVP, with several breeds genetically predisposed. As in humans, previous studies have suggested that canine MVP may be polygenic and may be associated with alterations in the}, number={9}, journal={Journal of the American College of Cardiology}, publisher={Elsevier BV}, author={Williams, Brian and Friedenberg, Steven G. and Meurs, Kathryn M.}, year={2019}, month={Mar}, pages={957} } @article{yost_friedenberg_jesty_olby_meurs_2019, title={The R9H phospholamban mutation is associated with highly penetrant dilated cardiomyopathy and sudden death in a spontaneous canine model}, volume={697}, ISSN={0378-1119}, url={http://dx.doi.org/10.1016/j.gene.2019.02.022}, DOI={10.1016/j.gene.2019.02.022}, abstractNote={Causative mutations for familial dilated cardiomyopathy (DCM) have been identified in the phospholamban gene. There are many poorly understood aspects about familial DCM (variable penetrance, expression) which may be studied in natural animal models. We characterized genetic aspects of familial DCM in a canine model with a high incidence of sudden death. A missense G > A mutation in exon 1 of the phospholamban gene that changed an amino acid from arginine to histidine was identified in affected dogs. This variant was predicted to be deleterious. We describe a spontaneous canine model of familial DCM and sudden death with the R9H mutation. In comparison to a reported human family, the variant was highly penetrant and resulted in sudden death. Genetic penetrance of this mutation may be influenced by genetic or environmental modifiers. The dog provides an excellent model in which to study complex aspects of familial DCM.}, journal={Gene}, publisher={Elsevier BV}, author={Yost, Oriana and Friedenberg, Steven G. and Jesty, Sophy A. and Olby, Natasha J. and Meurs, Kathryn M.}, year={2019}, month={May}, pages={118–122} } @article{friedenberg_vansteenkiste_yost_treeful_meurs_tokarz_olby_2018, title={A de novo mutation in the EXT2 gene associated with osteochondromatosis in a litter of American Staffordshire Terriers}, volume={32}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.15073}, DOI={10.1111/jvim.15073}, abstractNote={BackgroundWe aimed to identify mutations associated with osteochondromatosis in a litter of American Staffordshire Terrier puppies.HypothesisWe hypothesized that the associated mutation would be located in a gene that causes osteochondromatosis in humans.AnimalsA litter of 9 American Staffordshire puppies, their sire and dam, 3 of 4 grandparents, 26 healthy unrelated American Staffordshire Terriers, and 154 dogs of 27 different breeds.MethodsWhole genome sequencing was performed on the proband, and variants were compared against polymorphisms derived from 154 additional dogs across 27 breeds, as well as single nucleotide polymorphism database 146. One variant was selected for follow‐up sequencing. Parentage and genetic mosaicism were evaluated across the litter.ResultsWe found 56,301 genetic variants unique to the proband. Eleven variants were located in or near the gene exostosin 2 (EXT2), which is strongly associated with osteochondromatosis in humans. One heterozygous variant (c.969C > A) is predicted to result in a stop codon in exon 5 of the gene. Sanger sequencing identified the identical mutation in all affected offspring. The mutation was absent in the unaffected offspring, both parents, all available grandparents, and 26 healthy unrelated American Staffordshire Terriers.Conclusions and Clinical ImportanceThese findings represent the first reported mutation associated with osteochondromatosis in dogs. Because this mutation arose de novo, the identical mutation is unlikely to be the cause of osteochondromatosis in other dogs. However, de novo mutations in EXT2 are common in humans with osteochondromatosis, and by extension, it is possible that dogs with osteochondromatosis could be identified by sequencing the entire EXT2 gene.}, number={3}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Friedenberg, Steven G. and Vansteenkiste, Daniella and Yost, Oriana and Treeful, Amy E. and Meurs, Kathryn M. and Tokarz, Debra A. and Olby, Natasha J.}, year={2018}, month={Feb}, pages={986–992} } @article{gandolfi_alhaddad_abdi_bach_creighton_davis_decker_dodman_ginns_grahn_et al._2018, title={Applications and efficiencies of the first cat 63K DNA array}, volume={8}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/S41598-018-25438-0}, DOI={10.1038/S41598-018-25438-0}, abstractNote={AbstractThe development of high throughput SNP genotyping technologies has improved the genetic dissection of simple and complex traits in many species including cats. The properties of feline 62,897 SNPs Illumina Infinium iSelect DNA array are described using a dataset of over 2,000 feline samples, the most extensive to date, representing 41 cat breeds, a random bred population, and four wild felid species. Accuracy and efficiency of the array’s genotypes and its utility in performing population-based analyses were evaluated. Average marker distance across the array was 37,741 Kb, and across the dataset, only 1% (625) of the markers exhibited poor genotyping and only 0.35% (221) showed Mendelian errors. Marker polymorphism varied across cat breeds and the average minor allele frequency (MAF) of all markers across domestic cats was 0.21. Population structure analysis confirmed a Western to Eastern structural continuum of cat breeds. Genome-wide linkage disequilibrium ranged from 50–1,500 Kb for domestic cats and 750 Kb for European wildcats (Felis silvestris silvestris). Array use in trait association mapping was investigated under different modes of inheritance, selection and population sizes. The efficient array design and cat genotype dataset continues to advance the understanding of cat breeds and will support monogenic health studies across feline breeds and populations.}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Gandolfi, Barbara and Alhaddad, Hasan and Abdi, Mona and Bach, Leslie H. and Creighton, Erica K. and Davis, Brian W. and Decker, Jared E. and Dodman, Nicholas H. and Ginns, Edward I. and Grahn, Jennifer C. and et al.}, year={2018}, month={May} } @article{gandolfi_alhaddad_abdi_bach_creighton_davis_decker_dodman_grahn_grahn_et al._2018, title={Applications and efficiencies of the first cat 63K DNA array}, volume={8}, journal={Scientific Reports}, author={Gandolfi, B. and Alhaddad, H. and Abdi, M. and Bach, L. H. and Creighton, E. K. and Davis, B. W. and Decker, J. E. and Dodman, N. H. and Grahn, J. C. and Grahn, R. A. and et al.}, year={2018} } @article{gandolfi_alhaddad_abdi_bach_creighton_davis_decker_dodman_grahn_grahn_et al._2018, title={Applications and efficiencies of the first cat 63K DNA array (vol 8, 7024, 2018)}, volume={8}, journal={Scientific Reports}, author={Gandolfi, B. and Alhaddad, H. and Abdi, M. and Bach, L. H. and Creighton, E. K. and Davis, B. W. and Decker, J. E. and Dodman, N. H. and Grahn, J. C. and Grahn, R. A. and et al.}, year={2018} } @article{gandolfi_alhaddad_abdi_bach_creighton_davis_decker_dodman_ginns_grahn_et al._2018, title={Author Correction: Applications and efficiencies of the first cat 63K DNA array}, volume={8}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/S41598-018-26885-5}, DOI={10.1038/S41598-018-26885-5}, abstractNote={A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Gandolfi, Barbara and Alhaddad, Hasan and Abdi, Mona and Bach, Leslie H. and Creighton, Erica K. and Davis, Brian W. and Decker, Jared E. and Dodman, Nicholas H. and Ginns, Edward I. and Grahn, Jennifer C. and et al.}, year={2018}, month={Jun} } @inbook{meurs_2018, place={Philadelphia}, edition={XVI}, title={Cardiomyopathy in the boxer dog}, booktitle={Current Veterinary Therapy (Small Animal Practice)}, publisher={WB Saunders}, author={Meurs, K. M.}, editor={Scansen, B. and Bonagura, J.Editors}, year={2018} } @article{guevar_olby_meurs_yost_friedenberg_2018, title={Deafness and vestibular dysfunction in a Doberman Pinscher puppy associated with a mutation in the PTPRQ gene}, volume={32}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.15060}, DOI={10.1111/jvim.15060}, abstractNote={BackgroundA congenital syndrome of hearing loss and vestibular dysfunction affects Doberman Pinschers. Its inheritance pattern is suspected to be autosomal recessive and it potentially represents a spontaneous animal model of an autosomal recessive syndromic hearing loss.Hypothesis/ObjectivesThe objectives of this study were to use whole genome sequencing (WGS) to identify deleterious genetic variants in candidate genes associated with the syndrome and to study the prevalence of candidate variants among a population of unaffected Doberman Pinschers.AnimalsOne affected Doberman Pinscher and 202 unaffected Doberman Pinschers.MethodsWGS of the affected dog with filtering of variants against a database of 154 unaffected dogs of diverse breeds was performed. Confirmation of candidate variants was achieved by Sanger sequencing followed by genotyping of the control population of unaffected Doberman Pinschers.ResultsWGS and variant filtering identified an alteration in a gene associated with both deafness and vestibular disease in humans: protein tyrosine phosphatase, receptor type Q (PTPRQ). There was a homozygous A insertion at CFA15: 22 989 894, causing a frameshift mutation in exon 39 of the gene. This insertion is predicted to cause a protein truncation with a premature stop codon occurring after position 2054 of the protein sequence that causes 279 C‐terminal amino acids to be eliminated. Prevalence of the variant was 1.5% in a cohort of 202 unaffected Doberman Pinschers; all unaffected Doberman Pinschers were heterozygous or heterozygous for the reference allele.Conclusion and Clinical ImportanceWe report the identification of a genetic alteration on the PTPRQ gene that is associated with congenital hearing and vestibular disorder in a young Doberman Pinscher dog.}, number={2}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Guevar, Julien and Olby, Natasha J. and Meurs, Kathryn M. and Yost, Oriana and Friedenberg, Steven G.}, year={2018}, month={Feb}, pages={665–669} } @article{adin_defrancesco_keene_tou_meurs_atkins_aona_kurtz_barron_saker_et al._2019, title={Echocardiographic phenotype of canine dilated cardiomyopathy differs based on diet type}, volume={21}, ISSN={["1875-0834"]}, DOI={10.1016/j.jvc.2018.11.002}, abstractNote={{"Label"=>"INTRODUCTION", "NlmCategory"=>"BACKGROUND"} Canine dilated cardiomyopathy (DCM) can result from numerous etiologies including genetic mutations, infections, toxins, and nutritional imbalances. This study sought to characterize differences in echocardiographic findings between dogs with DCM fed grain-free (GF) diets and grain-based (GB) diets. {"Label"=>"ANIMALS", "NlmCategory"=>"METHODS"} Forty-eight dogs with DCM and known diet history. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} This was a retrospective analysis of dogs with DCM from January 1, 2015 to May 1, 2018 with a known diet history. Dogs were grouped by diet (GF and GB), and the GF group was further divided into dogs eating the most common grain-free diet (GF-1) and other grain-free diets (GF-o). Demographics, diet history, echocardiographic parameters, taurine concentrations, and vertebral heart scale were compared between GB, all GF, GF-1, and GF-o groups at diagnosis and recheck. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} Dogs eating GF-1 weighed less than GB and GF-o dogs, but age and sex were not different between groups. Left ventricular size in diastole and systole was greater, and sphericity index was less for GF-1 compared with GB dogs. Diastolic left ventricular size was greater for all GF compared with that of GB dogs. Fractional shortening, left atrial size, and vertebral heart scale were not different between groups. Taurine deficiency was not identified in GF dogs, and presence of congestive heart failure was not different between groups. Seven dogs that were reevaluated after diet change (6 received taurine supplementation) had clinical and echocardiographic improvement. {"Label"=>"CONCLUSIONS", "NlmCategory"=>"CONCLUSIONS"} Dietary-associated DCM occurs with some GF diets and can improve with nutritional management, including diet change. The role of taurine supplementation, even without deficiency, is uncertain.}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Adin, Darcy and DeFrancesco, Teresa and Keene, Bruce and Tou, Sandra and Meurs, Kathryn and Atkins, Clarke and Aona, Brent and Kurtz, Kari and Barron, Lara and Saker, Korinn and et al.}, year={2019}, month={Feb}, pages={1–9} } @inbook{meurs_2018, place={Philadelphia}, title={Genetic cardiac disease in the dog and cat}, booktitle={Current Veterinary Therapy (Small Animal Practice) XVI}, publisher={WB Saunders}, author={Meurs, K.M.}, year={2018} } @article{meurs_adin_k. o'donnell_keene_atkins_defrancesco_tou_2019, title={Myxomatous mitral valve disease in the miniature poodle: A retrospective study}, volume={244}, ISSN={["1532-2971"]}, DOI={10.1016/j.tvjl.2018.12.019}, abstractNote={Myxomatous mitral valve disease (MMVD) is the most common cardiovascular disease in the dog. The natural history of the disease is wide ranging and includes patients without clinical signs as well as those with significant clinical consequences from cardiac arrhythmias, pulmonary hypertension and/or congestive heart failure. The factors that determine which dogs remain asymptomatic and which develop clinical disease are not known. Disease characteristics could be breed or family related; some breeds of dogs, particularly the Cavalier King Charles spaniels, develop MMVD at an early age. The purpose of this study was to retrospectively characterize MMVD in the miniature poodle, a commonly affected breed in which MMVD has not been well characterized. Thirty-two miniature poodles met the inclusion criteria. Mean age was 11±three years. Clinical signs included exercise intolerance, syncope and coughing. Eighteen dogs were classified as ACVIM Stage B1, 12 as stage B2, and two as stage C. Mean vertebral heart scale (VHS) was 10.2 (±standard deviation of 0.9); 15 of 28 dogs had a VHS <10.3. One dog had radiographic evidence of congestive heart failure. Mean diastolic left ventricle dimension normalized to body weight was 1.6 (±0.4) and mean systolic was 0.8 (±0.3). Mitral valve prolapse was subjectively classified as mild or moderate in 19 dogs and severe in two. In the miniature poodles reported here, MMVD appears to be a fairly late onset disease and often is a mild phenotype.}, journal={VETERINARY JOURNAL}, author={Meurs, K. M. and Adin, D. and K. O'Donnell and Keene, B. W. and Atkins, C. E. and DeFrancesco, T. and Tou, S.}, year={2019}, month={Feb}, pages={94–97} } @article{lichtenberger_meurs_cote_2018, title={Preliminary Assessment of a Novel 14-Day Electrocardiographic Adhesive Patch Monitor in Dogs}, volume={54}, ISSN={["1547-3317"]}, DOI={10.5326/jaaha-ms-6626}, abstractNote={ABSTRACT Cardiac arrhythmias often are transient and might not be detected using conventional electrocardiographic (ECG) techniques. The adhesive patch monitor (APM) is a single-lead, lightweight, up to 14-day continuous ambulatory ECG monitor. This study aimed to prospectively assess its usability in four boxer dogs considered either to be healthy or to have arrhythmogenic right ventricular cardiomyopathy. Optimal recording was obtained by placing the APM on the left side of the animal’s thorax, at the fifth intercostal space, slightly dorsal to the costochondral junction, and oriented either vertically or parallel to the long axis of the heart. In three dogs, the APM remained attached for 14 days. One dog removed the APM after 59 hr. Skin irritation was documented in all dogs and resolved spontaneously after removal of the APM. The analyzable time was >93% of the total wear time and recordings provided an unambiguous rhythm diagnosis at rest. Walking, running, or playing caused intermittent motion artifact that could impair ECG interpretation. APM results were comparable to those obtained with 24-hr Holter monitoring. Extended continuous ECG monitoring with the APM is feasible in boxer dogs and provides interpretable recordings.}, number={3}, journal={JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION}, author={Lichtenberger, Jonathan and Meurs, Kathryn M. and Cote, Etienne}, year={2018}, pages={138–143} } @article{meurs_stern_atkins_adin_aona_condit_defrancesco_reina-doreste_keene_tou_et al._2017, title={Angiotensin-converting enzyme activity and inhibition in dogs with cardiac disease and an angiotensin-converting enzyme polymorphism}, volume={18}, ISSN={["1752-8976"]}, url={https://europepmc.org/articles/PMC5843865}, DOI={10.1177/1470320317737184}, abstractNote={Objective: The objective of this study was to evaluate angiotensin-converting enzyme (ACE) activity in dogs and with and without an ACE polymorphism in the canine ACE gene, before and after treatment with an ACE inhibitor. Methods: Thirty-one dogs (20 wild-type, 11 ACE polymorphism) with heart disease were evaluated with ACE activity measurement and systolic blood pressure before and after administration of an ACE inhibitor (enalapril). Results: Median pre-treatment ACE activity was significantly lower for ACE polymorphism dogs than for dogs with the wild-type sequence (P=0.007). After two weeks of an ACE inhibitor, ACE activity was significantly reduced for both genotypes (wild-type, P<0.0001; ACE polymorphism P=0.03); mean post-therapy ACE activity was no different between the groups. Conclusion: An ACE polymorphism is associated with lower levels of ACE activity. Dogs with the polymorphism still experience suppression of ACE activity in response to an ACE inhibitor. It is possible that the genetic status and ACE activity of dogs may impact the response of dogs with this variant to an ACE inhibitor.}, number={4}, journal={JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM}, author={Meurs, Kathryn M. and Stern, Joshua A. and Atkins, Clarke E. and Adin, Darcy and Aona, Brent and Condit, Julia and DeFrancesco, Teresa and Reina-Doreste, Yamir and Keene, Bruce W. and Tou, Sandy and et al.}, year={2017}, month={Oct} } @article{meurs_olsen_reimann_keene_atkins_adin_aona_condit_defrancesco_reina-doreste_et al._2018, title={Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease}, volume={28}, url={https://doi.org/10.1097/FPC.0000000000000322}, DOI={10.1097/FPC.0000000000000322}, abstractNote={Objectives Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is particularly common in the Cavalier King Charles Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin-converting enzyme inhibitors (ACE-I). We have previously identified a canine ACE gene polymorphism associated with a decrease in angiotensin-converting enzyme (ACE) activity. The aim of this study was to evaluate for the prevalence of the ACE polymorphism in CKCS with mitral valve disease and to determine whether the presence of the polymorphism is associated with alterations in ACE activity at different stages of cardiac disease. Methods Seventy-three dogs with a diagnosis of mitral valve disease were evaluated and a blood sample was drawn for ACE polymorphism genotyping and ACE activity measurement. Results Forty-three dogs were homozygous for the ACE polymorphism; five were heterozygous and 25 were homozygous wild type. The mean age and the median severity of disease were not different for dogs with the polymorphism and dogs with the wild-type sequence. The median baseline ACE activity was significantly lower for the ACE polymorphism (27.0 U/l) than the wild-type sequence dogs (31.0 U/l) (P=0.02). Dogs with more severe disease and the ACE polymorphism had significantly lower levels of ACE activity than dogs with the wild-type sequence (P=0.03). Conclusion The CKCS appears to have a high prevalence of the ACE variant. Dogs with the ACE variant had lower levels of ACE activity even in more advanced mitral valve disease than dogs without the variant. The clinical significance of this finding and its impact on the need for ACE-I in dogs with the polymorphism and heart disease deserves further study.}, number={2}, journal={Pharmacogenetics and Genomics}, author={Meurs, K.M. and Olsen, L.H. and Reimann, M.J. and Keene, B.W. and Atkins, C.E. and Adin, D. and Aona, B. and Condit, J. and DeFrancesco, T. and Reina-Doreste, Y. and et al.}, year={2018}, month={Feb}, pages={37–40} } @article{meurs_2017, title={Arrhythmogenic Right Ventricular Cardiomyopathy in the Boxer Dog: An Update}, volume={47}, ISSN={["1878-1306"]}, DOI={10.1016/j.cvsm.2017.04.007}, abstractNote={Arrhythmogenic right ventricular cardiomyopathy is an inheritable form of myocardial disease characterized most commonly by ventricular tachycardias, syncope, and sometimes systolic dysfunction and heart failure. A genetic mutation in the striatin gene has been identified in many affected dogs. Dogs with only one copy of the mutation (heterozygous) have a variable prognosis, with many dogs remaining asymptomatic or being successfully managed on antiarrhythmic drugs for years. Dogs that are homozygous for the mutation seem to have a worse prognosis.}, number={5}, journal={VETERINARY CLINICS OF NORTH AMERICA-SMALL ANIMAL PRACTICE}, author={Meurs, Kathryn M.}, year={2017}, month={Sep}, pages={1103-+} } @article{meurs_friedenberg_williams_keene_atkins_adin_aona_defrancesco_tou_mackay_et al._2018, title={Evaluation of genes associated with human myxomatous mitral valve disease in dogs with familial myxomatous mitral valve degeneration}, volume={232}, ISSN={["1532-2971"]}, DOI={10.1016/j.tvjl.2017.12.002}, abstractNote={Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is believed to be heritable in Cavalier King Charles spaniels (CKCS) and Dachshunds. Myxomatous mitral valve disease is a familial disease in human beings as well and genetic mutations have been associated with its development. We hypothesized that a genetic mutation associated with the development of the human form of MMVD was associated with the development of canine MMVD. DNA was isolated from blood samples from 10 CKCS and 10 Dachshunds diagnosed with MMVD, and whole genome sequences from each animal were obtained. Variant calling from whole genome sequencing data was performed using a standardized bioinformatics pipeline for all samples. After filtering, the canine genes orthologous to the human genes known to be associated with MMVD were identified and variants were assessed for likely pathogenic implications. No variant was found in any of the genes evaluated that was present in least eight of 10 affected CKCS or Dachshunds. Although mitral valve disease in the CKCS and Dachshund is a familial disease, we did not identify genetic cause in the genes responsible for the human disease in the dogs studied here.}, journal={VETERINARY JOURNAL}, author={Meurs, Kathryn and Friedenberg, S. G. and Williams, B. and Keene, B. W. and Atkins, C. E. and Adin, D. and Aona, B. and DeFrancesco, Teresa and Tou, S. and Mackay, T. and et al.}, year={2018}, month={Feb}, pages={16–19} } @article{hensley_tang_woodruff_defrancesco_tou_williams_breen_meurs_keene_cheng_et al._2017, title={Intracoronary allogeneic cardiosphere-derived stem cells are safe for use in dogs with dilated cardiomyopathy}, volume={21}, ISSN={1582-1838}, url={http://dx.doi.org/10.1111/jcmm.13077}, DOI={10.1111/jcmm.13077}, abstractNote={AbstractCardiosphere‐derived cells (CDCs) have been shown to reduce scar size and increase viable myocardium in human patients with mild/moderate myocardial infarction. Studies in rodent models suggest that CDC therapy may confer therapeutic benefits in patients with non‐ischaemic dilated cardiomyopathy (DCM). We sought to determine the safety and efficacy of allogeneic CDC in a large animal (canine) model of spontaneous DCM. Canine CDCs (cCDCs) were grown from a donor dog heart. Similar to human CDCs, cCDCs express CD105 and are slightly positive for c‐kit and CD90. Thirty million of allogeneic cCDCs was infused into the coronary vessels of Doberman pinscher dogs with spontaneous DCM. Adverse events were closely monitored, and cardiac functions were measured by echocardiography. No adverse events occurred during and after cell infusion. Histology on dog hearts (after natural death) revealed no sign of immune rejection from the transplanted cells.}, number={8}, journal={Journal of Cellular and Molecular Medicine}, publisher={Wiley}, author={Hensley, Michael Taylor and Tang, Junnan and Woodruff, Kathleen and Defrancesco, Teresa and Tou, Sandra and Williams, Christina M. and Breen, Mathew and Meurs, Kathryn and Keene, Bruce and Cheng, Ke and et al.}, year={2017}, month={Mar}, pages={1503–1512} } @inproceedings{talley_zimmer_bolotnov_2016, title={Coalescence prevention algorithm for level set method}, DOI={10.1115/fedsm2016-7608}, abstractNote={The application of interface tracking methods to bubbly flow modeling has grown in recent years due to improvements in computing performance and development of more efficient solvers. However, the standard formulation of most interface tracking methods is not designed to physically handle the interface interactions at reasonable grid sizes. Regardless of the method used, a high grid resolution is required in the liquid film region in order to properly model drainage process during bubble interaction, which in certain conditions prevents the coalescence. This makes large scale (many bubbles) simulations unaffordable. One of the popular interface tracking approached is the level-set (LS) method. To simulate realistic bubble coalescence behavior in the LS method an algorithm with the capability of delaying or preventing the process of multiple simultaneous coalescence events has been developed. Bubble interaction plays a significant role in high void fraction flow behavior and affects the transition to other flow regimes (e.g. churn-turbulent or slug flows). The described algorithm allows to improve the accuracy of predicting coalescence events in these relevant cases and has been tested in a variety of conditions and computational meshes. This novel algorithm uses the LS method field to detect when bubbles are in close proximity, indicating a potential coalescence event, and applies a subgrid scale force to simulate the unresolved liquid drainage force. The subgrid-model is introduced by locally modifying the surface tension force near the liquid film drainage area. The algorithm can also simulate the liquid drainage time of the thin film by controlling the length of time the increased surface tension has been applied. Thus a new method of modeling bubble coalescence has been developed. Several test cases were designed to demonstrate the capabilities of the algorithm. The simulations, including a mesh study, confirmed the abilities to identify and prevent coalescence as well as implement the time tracking portion, with an additional 10–25% computational cost. Ongoing tests aim to verify the algorithm’s functionality for simulations with different flow conditions, a ranging number of bubbles, and both structured and unstructured computational mesh types. Specifically, a bubble rising towards a free surface provides a test of performance and demonstrates the ability to consistently prevent coalescence. In addition, a two bubble case and a seven bubble case provide a more complex demonstration of how the algorithm performs for larger simulations. These cases are compared to much more expensive simulations capable of resolving the liquid film drainage (through very high local mesh resolution), to investigate how the algorithm replicates the liquid film drainage process.}, booktitle={Proceedings of the asme fluids engineering division summer meeting, 2016, vol 1b}, author={Talley, M. L. and Zimmer, M. D. and Bolotnov, I. A.}, year={2016} } @article{friedenberg_meurs_mackay_2016, title={Evaluation of artificial selection in Standard Poodles using whole-genome sequencing}, volume={27}, ISSN={0938-8990 1432-1777}, url={http://dx.doi.org/10.1007/S00335-016-9660-9}, DOI={10.1007/S00335-016-9660-9}, abstractNote={Identifying regions of artificial selection within dog breeds may provide insights into genetic variation that underlies breed-specific traits or diseases-particularly if these traits or disease predispositions are fixed within a breed. In this study, we searched for runs of homozygosity (ROH) and calculated the d i statistic (which is based upon F ST) to identify regions of artificial selection in Standard Poodles using high-coverage, whole-genome sequencing data of 15 Standard Poodles and 49 dogs across seven other breeds. We identified consensus ROH regions ≥1 Mb in length and common to at least ten Standard Poodles covering 0.6 % of the genome, and d i regions that most distinguish Standard Poodles from other breeds covering 3.7 % of the genome. Within these regions, we identified enriched gene pathways related to olfaction, digestion, and taste, as well as pathways related to adrenal hormone biosynthesis, T cell function, and protein ubiquitination that could contribute to the pathogenesis of some Poodle-prevalent autoimmune diseases. We also validated variants related to hair coat and skull morphology that have previously been identified as being under selective pressure in Poodles, and flagged additional polymorphisms in genes such as ITGA2B, CBX4, and TNXB that may represent strong candidates for other common Poodle disorders.}, number={11-12}, journal={Mammalian Genome}, publisher={Springer Nature}, author={Friedenberg, Steven G. and Meurs, Kathryn M. and Mackay, Trudy F. C.}, year={2016}, month={Aug}, pages={599–609} } @article{friedenberg_lunn_meurs_2016, title={Evaluation of the genetic basis of primary hypoadrenocorticism in Standard Poodles using SNP array genotyping and whole-genome sequencing}, volume={28}, ISSN={0938-8990 1432-1777}, url={http://dx.doi.org/10.1007/s00335-016-9671-6}, DOI={10.1007/s00335-016-9671-6}, abstractNote={Primary hypoadrenocorticism, also known as Addison's disease, is an autoimmune disorder leading to the destruction of the adrenal cortex and subsequent loss of glucocorticoid and mineralocorticoid hormones. The disease is prevalent in Standard Poodles and is believed to be highly heritable in the breed. Using genotypes derived from the Illumina Canine HD SNP array, we performed a genome-wide association study of 133 carefully phenotyped Standard Poodles (61 affected, 72 unaffected) and found no markers significantly associated with the disease. We also sequenced the entire genomes of 20 Standard Poodles (13 affected, 7 unaffected) and analyzed the data to identify common variants (including SNPs, indels, structural variants, and copy number variants) across affected dogs and variants segregating within a single pedigree of highly affected dogs. We identified several candidate genes that may be fixed in both Standard Poodles and a small population of dogs of related breeds. Further studies are required to confirm these findings more broadly, as well as additional gene-mapping efforts aimed at fully understanding the genetic basis of what is likely a complex inherited disorder.}, number={1-2}, journal={Mammalian Genome}, publisher={Springer Nature}, author={Friedenberg, Steven G. and Lunn, Katharine F. and Meurs, Kathryn M.}, year={2016}, month={Nov}, pages={56–65} } @article{friedenberg_meurs_2016, title={Genotype imputation in the domestic dog}, volume={27}, ISSN={["1432-1777"]}, DOI={10.1007/s00335-016-9636-9}, abstractNote={Application of imputation methods to accurately predict a dense array of SNP genotypes in the dog could provide an important supplement to current analyses of array-based genotyping data. Here, we developed a reference panel of 4,885,283 SNPs in 83 dogs across 15 breeds using whole genome sequencing. We used this panel to predict the genotypes of 268 dogs across three breeds with 84,193 SNP array-derived genotypes as inputs. We then (1) performed breed clustering of the actual and imputed data; (2) evaluated several reference panel breed combinations to determine an optimal reference panel composition; and (3) compared the accuracy of two commonly used software algorithms (Beagle and IMPUTE2). Breed clustering was well preserved in the imputation process across eigenvalues representing 75 % of the variation in the imputed data. Using Beagle with a target panel from a single breed, genotype concordance was highest using a multi-breed reference panel (92.4 %) compared to a breed-specific reference panel (87.0 %) or a reference panel containing no breeds overlapping with the target panel (74.9 %). This finding was confirmed using target panels derived from two other breeds. Additionally, using the multi-breed reference panel, genotype concordance was slightly higher with IMPUTE2 (94.1 %) compared to Beagle; Pearson correlation coefficients were slightly higher for both software packages (0.946 for Beagle, 0.961 for IMPUTE2). Our findings demonstrate that genotype imputation from SNP array-derived data to whole genome-level genotypes is both feasible and accurate in the dog with appropriate breed overlap between the target and reference panels.}, number={9-10}, journal={MAMMALIAN GENOME}, author={Friedenberg, S. G. and Meurs, K. M.}, year={2016}, month={Oct}, pages={485–494} } @article{friedenberg_brown_meurs_law_2018, title={Lymphocyte Subsets in the Adrenal Glands of Dogs With Primary Hypoadrenocorticism}, volume={55}, ISSN={["1544-2217"]}, DOI={10.1177/0300985816684914}, abstractNote={ Primary hypoadrenocorticism, or Addison’s disease, is an autoimmune condition common in certain dog breeds that leads to the destruction of the adrenal cortex and a clinical syndrome involving anorexia, gastrointestinal upset, and electrolyte imbalances. Previous studies have demonstrated that this destruction is strongly associated with lymphocytic-plasmacytic inflammation and that the lymphocytes are primarily T cells. In this study, we used both immunohistochemistry and in situ hybridization to characterize the T-cell subtypes involved. We collected postmortem specimens of 5 dogs with primary hypoadrenocorticism and 2 control dogs and, using the aforementioned techniques, showed that the lymphocytes are primarily CD4+ rather than CD8+. These findings have important implications for improving our understanding of the pathogenesis and in searching for the underlying causative genetic polymorphisms. }, number={1}, journal={VETERINARY PATHOLOGY}, author={Friedenberg, S. G. and Brown, D. L. and Meurs, K. M. and Law, J. McHugh}, year={2018}, month={Jan}, pages={177–181} } @article{friedenberg_chdid_keene_sherry_motsinger-reif_meurs_2016, title={Use of RNA-seq to identify cardiac genes and gene pathways differentially expressed between dogs with and without dilated cardiomyopathy}, volume={77}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.77.7.693}, abstractNote={Abstract OBJECTIVE To identify cardiac tissue genes and gene pathways differentially expressed between dogs with and without dilated cardiomyopathy (DCM). ANIMALS 8 dogs with and 5 dogs without DCM. PROCEDURES Following euthanasia, samples of left ventricular myocardium were collected from each dog. Total RNA was extracted from tissue samples, and RNA sequencing was performed on each sample. Samples from dogs with and without DCM were grouped to identify genes that were differentially regulated between the 2 populations. Overrepresentation analysis was performed on upregulated and downregulated gene sets to identify altered molecular pathways in dogs with DCM. RESULTS Genes involved in cellular energy metabolism, especially metabolism of carbohydrates and fats, were significantly downregulated in dogs with DCM. Expression of cardiac structural proteins was also altered in affected dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that RNA sequencing may provide important insights into the pathogenesis of DCM in dogs and highlight pathways that should be explored to identify causative mutations and develop novel therapeutic interventions.}, number={7}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Friedenberg, Steven G. and Chdid, Lhoucine and Keene, Bruce and Sherry, Barbara and Motsinger-Reif, Alison and Meurs, Kathryn M.}, year={2016}, month={Jul}, pages={693–699} } @article{meurs_weidman_rosenthal_lahmers_friedenberg_2016, title={Ventricular arrhythmias in Rhodesian Ridgebacks with a family history of sudden death and results of a pedigree analysis for potential inheritance patterns}, volume={248}, ISSN={["1943-569X"]}, DOI={10.2460/javma.248.10.1135}, abstractNote={Abstract OBJECTIVE To evaluate a group of related Rhodesian Ridgebacks with a family history of sudden death for the presence of arrhythmia and to identify possible patterns of disease inheritance among these dogs. DESIGN Prospective case series and pedigree investigation. ANIMALS 25 Rhodesian Ridgebacks with shared bloodlines. PROCEDURES Pedigrees of 4 young dogs (1 female and 3 males; age, 7 to 12 months) that died suddenly were evaluated, and owners of closely related dogs were asked to participate in the study. Dogs were evaluated by 24-hour Holter monitoring, standard ECG, echocardiography, or some combination of these to assess cardiac status. Necropsy reports, if available, were reviewed. RESULTS 31 close relatives of the 4 deceased dogs were identified. Of 21 dogs available for examination, 8 (2 males and 6 females) had ventricular tachyarrhythmias (90 to 8,700 ventricular premature complexes [VPCs]/24 h). No dogs had clinical signs of cardiac disease reported. Echocardiographic or necropsy evaluation for 7 of 12 dogs deemed affected (ie, with frequent or complex VPCs or sudden death) did not identify structural lesions. Five of 6 screened parents of affected dogs had 0 to 5 VPCs/24 h (all singlets), consistent with a normal reading. Pedigree evaluation suggested an autosomal recessive pattern of inheritance, but autosomal dominant inheritance with incomplete penetrance could not be ruled out. CONCLUSIONS AND CLINICAL RELEVANCE Holter monitoring of Rhodesian Ridgebacks with a family history of an arrhythmia or sudden death is recommended for early diagnosis of disease. An autosomal recessive pattern of inheritance in the studied dogs was likely, and inbreeding should be strongly discouraged.}, number={10}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Meurs, Kathryn M. and Weidman, Jess A. and Rosenthal, Steven L. and Lahmers, Kevin K. and Friedenberg, Steven G.}, year={2016}, month={May}, pages={1135–1138} } @inbook{meurs_2015, place={Philadelphia}, edition={10th}, title={Antiarrhythmic Agents}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell}, author={Meurs, K.M.}, year={2015} } @inbook{meurs_stern_2015, edition={8th}, title={Basic veterinary genetics}, booktitle={Ettinger’s Textbook of Veterinary Internal Medicine}, publisher={Elsevier, St Louis}, author={Meurs, K.M. and Stern, J.A.}, year={2015} } @article{hensley_andrade_keene_meurs_tang_wang_caranasos_piedrahita_li_cheng_et al._2015, title={Cardiac regenerative potential of cardiosphere-derived cells from adult dog hearts}, volume={19}, ISSN={1582-1838}, url={http://dx.doi.org/10.1111/jcmm.12585}, DOI={10.1111/jcmm.12585}, abstractNote={AbstractThe regenerative potential of cardiosphere‐derived cells (CDCs) for ischaemic heart disease has been demonstrated in mice, rats, pigs and a recently completed clinical trial. The regenerative potential of CDCs from dog hearts has yet to be tested. Here, we show that canine CDCs can be produced from adult dog hearts. These cells display similar phenotypes in comparison to previously studied CDCs derived from rodents and human beings. Canine CDCs can differentiate into cardiomyocytes, smooth muscle cells and endothelial cells in vitro. In addition, conditioned media from canine CDCs promote angiogenesis but inhibit cardiomyocyte death. In a doxorubicin‐induced mouse model of dilated cardiomyopathy (DCM), intravenous infusion of canine CDCs improves cardiac function and decreases cardiac fibrosis. Histology revealed that injected canine CDCs engraft in the mouse heart and increase capillary density. Out study demonstrates the regenerative potential of canine CDCs in a mouse model of DCM.}, number={8}, journal={Journal of Cellular and Molecular Medicine}, publisher={Wiley}, author={Hensley, M. T. and Andrade, J. and Keene, B. and Meurs, Kathryn and Tang, J. N. and Wang, Z. G. and Caranasos, T. G. and Piedrahita, J. and Li, T. S. and Cheng, K. and et al.}, year={2015}, month={Apr}, pages={1805–1813} } @inbook{meurs_stern_2015, edition={8th}, title={Clinical veterinary genetics}, booktitle={Ettinger’s Textbook of Veterinary Internal Medicine}, publisher={Elsevier, St Louis}, author={Meurs, K.M. and Stern, J.A.}, year={2015} } @article{friedenberg_buhrman_chdid_olby_olivry_guillaumin_o’toole_goggs_kennedy_rose_et al._2015, title={Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs}, volume={68}, ISSN={0093-7711 1432-1211}, url={http://dx.doi.org/10.1007/s00251-015-0894-6}, DOI={10.1007/s00251-015-0894-6}, abstractNote={Immune-mediated diseases are common and life-threatening disorders in dogs. Many canine immune-mediated diseases have strong breed predispositions and are believed to be inherited. However, the genetic mutations that cause these diseases are mostly unknown. As many immune-mediated diseases in humans share polymorphisms among a common set of genes, we conducted a candidate gene study of 15 of these genes across four immune-mediated diseases (immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, immune-mediated polyarthritis (IMPA), and atopic dermatitis) in 195 affected and 206 unaffected dogs to assess whether causative or predictive polymorphisms might exist in similar genes in dogs. We demonstrate a strong association (Fisher's exact p = 0.0004 for allelic association, p = 0.0035 for genotypic association) between two polymorphic positions (10 bp apart) in exon 2 of one allele in DLA-79, DLA-79*001:02, and multiple immune-mediated diseases. The frequency of this allele was significantly higher in dogs with immune-mediated disease than in control dogs (0.21 vs. 0.12) and ranged from 0.28 in dogs with IMPA to 0.15 in dogs with atopic dermatitis. This allele has two non-synonymous substitutions (compared with the reference allele, DLA-79*001:01), resulting in F33L and N37D amino acid changes. These mutations occur in the peptide-binding pocket of the protein, and based upon our computational modeling studies, are likely to affect critical interactions with the peptide N-terminus. Further studies are warranted to confirm these findings more broadly and to determine the specific mechanism by which the identified variants alter canine immune system function.}, number={3}, journal={Immunogenetics}, publisher={Springer Science and Business Media LLC}, author={Friedenberg, Steven G. and Buhrman, Greg and Chdid, Lhoucine and Olby, Natasha J. and Olivry, Thierry and Guillaumin, Julien and O’Toole, Theresa and Goggs, Robert and Kennedy, Lorna J. and Rose, Robert B. and et al.}, year={2015}, month={Dec}, pages={205–217} } @inbook{meurs_2016, title={Genetics of Feline Heart Disease}, volume={7}, ISBN={9780323226523}, url={http://dx.doi.org/10.1016/b978-0-323-22652-3.00040-2}, DOI={10.1016/b978-0-323-22652-3.00040-2}, booktitle={August's Consultations in Feline Internal Medicine}, publisher={Elsevier}, author={Meurs, Kathryn M.}, year={2016}, pages={412–416} } @article{stern_lahmers_meurs_2015, title={Identification of striatin, a desmosomal protein, in the canine corneal epithelium}, volume={102}, ISSN={["1532-2661"]}, url={https://doi.org/10.1016/j.rvsc.2015.08.009}, DOI={10.1016/j.rvsc.2015.08.009}, abstractNote={Striatin is a scaffolding protein expressed in brain and cardiac tissues. In the heart, striatin has been localized to the region of the cardiac desmosome. A causal mutation within the gene encoding for this scaffolding protein has been described as the etiology for arrhythmogenic right ventricular cardiomyopathy, a disease of the cardiac desmosome, in a canine model. Hemidesmosomes are cell adhesion complexes located within the cornea where they anchor the corneal epithelium to the stroma at the basement membrane and participate in cell-signaling processes. Traditional cell adhesion desmosomes are also known to link the corneal epithelial cells together. We hypothesized that striatin may be found in the cornea localized to regions of either hemidesmosomes and/or desmosomes. Immunohistochemical evaluation was performed to evaluate for striatin labeling in normal canine cornea. Striatin was localized to the cytoplasmic region of corneal epithelial cells. The role of striatin in corneal disease warrants investigation.}, journal={RESEARCH IN VETERINARY SCIENCE}, author={Stern, Joshua A. and Lahmers, Sunshine and Meurs, Kathryn M.}, year={2015}, month={Oct}, pages={182–183} } @article{meurs_stern_reina-doreste_maran_chdid_lahmers_keene_mealey_2015, title={Impact of the canine double-deletion beta 1 adrenoreceptor polymorphisms on protein structure and heart rate response to atenolol, a beta 1-selective beta-blocker}, volume={25}, ISSN={["1744-6880"]}, url={https://doi.org/10.1097/FPC.0000000000000152}, DOI={10.1097/fpc.0000000000000152}, abstractNote={Objective &bgr;-Adrenergic receptor antagonists are widely utilized for the management of cardiac diseases in dogs. We have recently identified two deletion polymorphisms in the canine adrenoreceptor 1 (ADRB1) gene. We hypothesized that canine ADRB1 deletions would alter the structure of the protein, as well as the heart rate response to the &bgr;-adrenergic receptor antagonist, atenolol. The objectives of this study were to predict the impact of these deletions on the predicted structure of the protein and on the heart rate response to atenolol in a population of healthy adult dogs. Methods Eighteen apparently healthy, mature dogs with (11) and without (seven) ADRB1 deletions were evaluated. The heart rate of the dogs was evaluated with a baseline ambulatory ECG before and 14–21 days after atenolol therapy (1 mg/kg orally q12 h). Minimum, average, and maximum heart rates were compared between groups of dogs (deletions, controls) using an unpaired t-test and within each group of dogs using a paired t-test. The protein structure of ADRB1 was predicted by computer modeling. Results Deletions were predicted to alter the structure of the ADRB1 protein. The heart rates of the dogs with deletions were lower than those of the control dogs (the average heart rates were significantly lower). Conclusion ADRB1 deletions appear to have structural and functional consequences. Individual genome-based treatment recommendations could impact the management of dogs with heart disease.}, number={9}, journal={PHARMACOGENETICS AND GENOMICS}, author={Meurs, Kathryn M. and Stern, Josh A. and Reina-Doreste, Yamir and Maran, Brian A. and Chdid, Lhoucine and Lahmers, Sunshine and Keene, Bruce W. and Mealey, Katrina L.}, year={2015}, month={Sep}, pages={427–431} } @article{meurs_chdid_reina-doreste_stern_2015, title={Polymorphisms in the canine and feline renin-angiotensin-aldosterone system genes}, volume={46}, ISSN={["1365-2052"]}, url={https://doi.org/10.1111/age.12260}, DOI={10.1111/age.12260}, abstractNote={Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.}, number={2}, journal={ANIMAL GENETICS}, author={Meurs, Kathryn M. and Chdid, Lhoucine and Reina-Doreste, Yamir and Stern, Joshua A.}, year={2015}, month={Apr}, pages={226–226} } @inbook{stern_meurs_2015, place={Philadelphia}, edition={7th}, title={Primary myocardial disease in the dog}, booktitle={Textbook of Veterinary Internal Medicine}, publisher={WB Saunders}, author={Stern, J.A. and Meurs, K.M.}, year={2015}, pages={1320–1328} } @article{ware_reina-doreste_stern_meurs_2015, title={Sudden Death Associated with QT Interval Prolongation and KCNQ1 Gene Mutation in a Family of English Springer Spaniels}, volume={29}, ISSN={["1939-1676"]}, url={https://europepmc.org/articles/PMC4895492}, DOI={10.1111/jvim.12550}, abstractNote={BackgroundA 5‐year‐old, healthy English Springer Spaniel died suddenly 4 months after delivering a litter of 7 puppies. Within 4 months of the dam's death, 3 offspring also died suddenly.HypothesisAbnormal cardiac repolarization, caused by an inherited long QT syndrome, is thought to be responsible for arrhythmias leading to sudden death in this family.AnimalsFour remaining dogs from the affected litter and 11 related dogs.MethodsPhysical examination and resting ECG were done on the littermates and 9 related dogs. Additional tests on some or all littermates included echocardiogram with Doppler, Holter monitoring, and routine serum biochemistry. Blood for DNA sequencing was obtained from all 15 dogs.ResultsThree of 4 littermates examined, but no other dogs, had prolonged QT intervals with unique T‐wave morphology. DNA sequencing of the KCNQ1 gene identified a heterozygous single base pair mutation, unique to these 3 dogs, which changes a conserved amino acid from threonine to lysine and is predicted to change protein structure.Conclusions and Clinical ImportanceThis family represents the first documentation in dogs of spontaneous familial QT prolongation, which was associated with a KCNQ1 gene mutation and sudden death. Although the final rhythm could not be documented in these dogs, their phenotypic manifestations of QT interval prolongation and abnormal ECG restitution suggested increased risk for sudden arrhythmic death. The KCNQ1 gene mutation identified is speculated to impair the cardiac repolarizing current IKs, similar to KCNQ1 mutations causing long QT syndrome 1 in humans.}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Ware, W. A. and Reina-Doreste, Y. and Stern, J. A. and Meurs, K. M.}, year={2015}, pages={561–568} } @article{kittleson_meurs_harris_2015, title={The genetic basis of hypertrophic cardiomyopathy in cats and humans}, volume={17}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2015.03.001}, DOI={10.1016/j.jvc.2015.03.001}, abstractNote={Mutations in genes that encode for muscle sarcomeric proteins have been identified in humans and two breeds of domestic cats with hypertrophic cardiomyopathy (HCM). This article reviews the history, genetics, and pathogenesis of HCM in the two species in order to give veterinarians a perspective on the genetics of HCM. Hypertrophic cardiomyopathy in people is a genetic disease that has been called a disease of the sarcomere because the preponderance of mutations identified that cause HCM are in genes that encode for sarcomeric proteins (Maron and Maron, 2013). Sarcomeres are the basic contractile units of muscle and thus sarcomeric proteins are responsible for the strength, speed, and extent of muscle contraction. In people with HCM, the two most common genes affected by HCM mutations are the myosin heavy chain gene (MYH7), the gene that encodes for the motor protein β-myosin heavy chain (the sarcomeric protein that splits ATP to generate force), and the cardiac myosin binding protein-C gene (MYBPC3), a gene that encodes for the closely related structural and regulatory protein, cardiac myosin binding protein-C (cMyBP-C). To date, the two mutations linked to HCM in domestic cats (one each in Maine Coon and Ragdoll breeds) also occur in MYBPC3 (Meurs et al., 2005, 2007). This is a review of the genetics of HCM in both humans and domestic cats that focuses on the aspects of human genetics that are germane to veterinarians and on all aspects of feline HCM genetics.}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Kittleson, Mark D. and Meurs, Kathryn M. and Harris, Samantha P.}, year={2015}, month={Dec}, pages={S53–S73} } @article{borgeat_stern_meurs_fuentes_connolly_2015, title={The influence of clinical and genetic factors on left ventricular wall thickness in Ragdoll cats}, volume={17}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2015.06.005}, DOI={10.1016/j.jvc.2015.06.005}, abstractNote={To investigate the effect of various genetic and environmental modifiers on left ventricular (LV) wall thickness in a cohort of cats genotyped for the myosin binding protein C3 mutation (MYBPC3).Sixty-four Ragdoll cats.All cats were screened for HCM with echocardiography and genotyping for the HCM-associated MYBPC3:R820W mutation. Cats were also genotyped for previously identified variant polymorphisms of the angiotensin-converting enzyme (ACE) and cardiac beta-adrenergic receptor (ADRB1) genes. Plasma N-terminal pro-B-type natriuretic peptide and cardiac troponin I were also measured. Associations were evaluated between genotype (MYBPC3 negative/positive, and ACE and ADRB1 negative/heterozygous/homozygous), patient factors (body weight, age and sex) and echocardiographic measurements of LV wall thickness.Male cats had greater maximum wall thickness (LVmax; 5.8 mm, IQR 5.1-6.4 mm) than females (4.7 mm, IQR 4.4-5.3 mm, p = 0.002). Body weight positively correlated with LVmax (ρ = 0.604, p < 0.001). The MYBPC3:R820W-positive cats had a greater LVmax (5.44 mm, IQR 4.83-6.28 mm) than the negative cats (4.76 mm, IQR 4.36-5.32 mm, p = 0.001). Also, the ACE polymorphism genotype was associated with LVmax: the homozygous cats (5.37 mm, IQR 5.14-6.4 mm) had greater LVmax than the heterozygous cats (4.73 mm, IQR 4.41-5.55 mm, p = 0.014). Only the MYBPC3 genotype and body weight were independently associated with wall thickness in multivariable analysis.This study provides evidence that the MYBPC3:R820W mutation is independently associated with LV wall thickness in Ragdoll cats. Body weight is also independently associated with maximum LV wall thickness, but is not currently accounted for in HCM screening. In addition, other genetic modifiers may be associated with variation in LV wall thickness in Ragdolls.}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Borgeat, Kieran and Stern, Joshua and Meurs, Kathryn M. and Fuentes, Virginia Luis and Connolly, David J.}, year={2015}, month={Dec}, pages={S258–S267} } @article{stern_white_lehmkuhl_reina-doreste_ferguson_nascone-yoder_meurs_2014, title={A single codon insertion in PICALM is associated with development of familial subvalvular aortic stenosis in Newfoundland dogs}, volume={133}, ISSN={0340-6717 1432-1203}, url={http://dx.doi.org/10.1007/s00439-014-1454-0}, DOI={10.1007/s00439-014-1454-0}, abstractNote={Familial subvalvular aortic stenosis (SAS) is one of the most common congenital heart defects in dogs and is an inherited defect of Newfoundlands, golden retrievers and human children. Although SAS is known to be inherited, specific genes involved in Newfoundlands with SAS have not been defined. We hypothesized that SAS in Newfoundlands is inherited in an autosomal dominant pattern and caused by a single genetic variant. We studied 93 prospectively recruited Newfoundland dogs, and 180 control dogs of 30 breeds. By providing cardiac screening evaluations for Newfoundlands we conducted a pedigree evaluation, genome-wide association study and RNA sequence analysis to identify a proposed pattern of inheritance and genetic loci associated with the development of SAS. We identified a three-nucleotide exonic insertion in phosphatidylinositol-binding clathrin assembly protein (PICALM) that is associated with the development of SAS in Newfoundlands. Pedigree evaluation best supported an autosomal dominant pattern of inheritance and provided evidence that equivocally affected individuals may pass on SAS in their progeny. Immunohistochemistry demonstrated the presence of PICALM in the canine myocardium and area of the subvalvular ridge. Additionally, small molecule inhibition of clathrin-mediated endocytosis resulted in developmental abnormalities within the outflow tract (OFT) of Xenopus laevis embryos. The ability to test for presence of this PICALM insertion may impact dog-breeding decisions and facilitate reduction of SAS disease prevalence in Newfoundland dogs. Understanding the role of PICALM in OFT development may aid in future molecular and genetic investigations into other congenital heart defects of various species.}, number={9}, journal={Human Genetics}, publisher={Springer Nature}, author={Stern, Joshua A. and White, Stephen N. and Lehmkuhl, Linda B. and Reina-Doreste, Yamir and Ferguson, Jordan L. and Nascone-Yoder, Nanette M. and Meurs, Kathryn M.}, year={2014}, month={Jun}, pages={1139–1148} } @article{reina-doreste_stern_keene_tou_atkins_defrancesco_ames_hodge_meurs_2014, title={Case-control study of the effects of pimobendan on survival time in cats with hypertrophic cardiomyopathy and congestive heart failure}, volume={245}, ISSN={["1943-569X"]}, url={https://doi.org/10.2460/javma.245.5.534}, DOI={10.2460/javma.245.5.534}, abstractNote={Abstract Objective—To assess survival time and adverse events related to the administration of pimobendan to cats with congestive heart failure (CHF) secondary to hypertrophic cardiomyopathy (HCM) or hypertrophic obstructive cardiomyopathy (HOCM). Design—Retrospective case-control study. Animals—27 cats receiving treatment with pimobendan and 27 cats receiving treatment without pimobendan. Procedures—Medical records between 2003 and 2013 were reviewed. All cats with HCM or HOCM treated with a regimen that included pimobendan (case cats) were identified. Control cats (cats with CHF treated during the same period with a regimen that did not include pimobendan) were selected by matching to case cats on the basis of age, sex, body weight, type of cardiomyopathy, and manifestation of CHF. Data collected included signalment, physical examination findings, echocardiographic data, serum biochemical values, and survival time from initial diagnosis of CHF. Kaplan-Meier survival curves were constructed and compared by means of a log rank test. Results—Cats receiving pimobendan had a significant benefit in survival time. Median survival time of case cats receiving pimobendan was 626 days, whereas median survival time for control cats not receiving pimobendan was 103 days. No significant differences were detected for any other variable. Conclusions and Clinical Relevance—The addition of pimobendan to traditional treatment for CHF may provide a substantial clinical benefit in survival time for HCM-affected cats with CHF and possibly HOCM-affected cats with CHF.}, number={5}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Reina-Doreste, Yamir and Stern, Joshua A. and Keene, Bruce W. and Tou, Sandra P. and Atkins, Clarke E. and DeFrancesco, Teresa C. and Ames, Marisa K. and Hodge, Timothy E. and Meurs, Kathryn M.}, year={2014}, month={Sep}, pages={534–539} } @article{meurs_stern_reina-doreste_spier_koplitz_baumwart_2014, title={Natural History of Arrhythmogenic Right Ventricular Cardiomyopathy in the Boxer Dog: A Prospective Study}, volume={28}, ISSN={["1939-1676"]}, url={https://europepmc.org/articles/PMC4857953}, DOI={10.1111/jvim.12385}, abstractNote={BackgroundBoxer arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease that may result in sudden death or heart failure.Hypothesis/objectivesTo prospectively study the natural history of Boxer ARVC.Animals72 dogs (49 ARVC, 23 controls).MethodsBoxers >1 year of age were recruited for annual reevaluation. Controls were defined as being ≥6 years of age and having <50 ventricular premature complex (VPCs)/24 h. ARVC was defined as ≥300 VPCs/24 h in the absence of other disease. Dogs were genotyped for the striatin deletion when possible. Descriptive statistics were determined for age; VPC number; annual change in VPC number; and left ventricular (LV) echocardiographic dimensions. Survival time was calculated.ResultsControls: median age of 7 years (range, 6–10); number of VPCs 12 (range, 4–32). Median time in study of 6 years (range, 2–9). Seventeen of 23 were genotyped (5 positive, 12 negative).ARVC: median age of diagnosis of 6 (range, 1–11). Median time in study 5 years (range, 3–8). A total of 33% were syncopal and 43/49 were genotyped (36 positive, 7 negative). Yearly change in VPCs was 46 (range, −7,699 to 33,524). Annual percentage change in LV dimensions was 0, and change in fractional shortening (FS%) was 2%. Two dogs had FS% <20%. Although ARVC dogs died suddenly, there was no difference in survival time between groups. ARVC median age of survival was 11 years, and for controls was 10 years.Conclusions/Clinical ImportanceArrhythmogenic right ventricular cardiomyopathy is a disease of middle age and frequently is associated with the striatin deletion. Syncope occurs in approximately 1/3 of affected dogs; systolic dysfunction is uncommon. The prognosis in many affected dogs is good.}, number={4}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Meurs, K. M. and Stern, J. A. and Reina-Doreste, Y. and Spier, A. W. and Koplitz, S. L. and Baumwart, R. D.}, year={2014}, pages={1214–1220} } @article{meurs_stern_sisson_kittleson_cunningham_ames_atkins_defrancesco_hodge_keene_et al._2013, title={Association of Dilated Cardiomyopathy with the Striatin Mutation Genotype in Boxer Dogs}, volume={27}, ISSN={["1939-1676"]}, url={https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jvim.12163}, DOI={10.1111/jvim.12163}, abstractNote={BackgroundMyocardial disease in the Boxer dog is characterized by 1 of 2 clinical presentations, dilated cardiomyopathy (DCM) characterized by ventricular systolic dysfunction, dilatation and tachyarrhythmias, and arrhythmogenic right ventricular cardiomyopathy (ARVC) characterized by ventricular tachyarrhythmias, syncope, and sudden death. Boxer ARVC has been associated with a deletion in the striatin gene in some families.Hypothesis/ObjectivesWe hypothesized that both presentations represent a single disease, and the development of DCM in the Boxer is associated with the striatin deletion.AnimalsThirty‐three adult Boxer dogs with DCM, 29 adult Boxer dogs with the striatin deletion and ARVC, and 16 Boxers without cardiac disease.MethodsDNA samples were evaluated for the striatin deletion. Association of the deletion with the DCM phenotype was tested by a Fisher's exact test. T‐tests were used to evaluate potential differences between the positive heterozygous and positive homozygous groups with DCM with regard to age, LVIDD, LVIDS, and FS%.ResultsThirty of 33 dogs with DCM were positive for the striatin deletion. The striatin mutation and the homozygous genotype were strongly associated with the DCM phenotype (P < .001 and P = .005). There was no statistical difference between the heterozygous and homozygous groups with regard to age and echocardiographic measurements.Conclusions and Clinical ImportanceThis study demonstrates an association between DCM in the Boxer dog and the striatin mutation, particularly with the homozygous genotype. The observation that 3/33 dogs developed DCM and lacked the striatin mutation suggests that there is at least 1 other cause of DCM in the Boxer dog.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Meurs, K. M. and Stern, J. A. and Sisson, D. D. and Kittleson, M. D. and Cunningham, S. M. and Ames, M. K. and Atkins, C. E. and DeFrancesco, T. and Hodge, T. E. and Keene, B. W. and et al.}, year={2013}, month={Nov}, pages={1437–1440} } @inbook{meurs_2013, place={Philadelphia}, title={Cardiomyopathy in the boxer dog}, booktitle={Current Veterinary Therapy (Small Animal Practice) XV}, publisher={WB Saunders}, author={Meurs, K.M.}, year={2013} } @article{stern_white_meurs_2013, title={Extent of linkage disequilibrium in large-breed dogs: chromosomal and breed variation}, volume={24}, ISSN={["1432-1777"]}, url={https://doi.org/10.1007/s00335-013-9474-y}, DOI={10.1007/s00335-013-9474-y}, abstractNote={The aim of this study was to better define the extent of linkage disequilibrium (LD) in populations of large-breed dogs and its variation by breed and chromosomal region. Understanding the extent of LD is a crucial component for successful utilization of genome-wide association studies and allows researchers to better define regions of interest and target candidate genes. Twenty-four Golden Retriever dogs, 28 Rottweiler dogs, and 24 Newfoundland dogs were genotyped for single-nucleotide polymorphism (SNP) data using a high-density SNP array. LD was calculated for all autosomes using Haploview. Decay of the squared correlation coefficient (r (2)) was plotted on a per-breed and per-chromosome basis as well as in a genome-wide fashion. The point of 50 % decay of r (2) was used to estimate the difference in extent of LD between breeds. Extent of LD was significantly shorter for Newfoundland dogs based upon 50 % decay of r (2) data at a mean of 344 kb compared to Golden Retriever and Rottweiler dogs at 715 and 834 kb, respectively (P < 0.0001). Notable differences in LD by chromosome were present within each breed and not strictly related to the length of the corresponding chromosome. Extent of LD is breed and chromosome dependent. To our knowledge, this is the first report of SNP-based LD for Newfoundland dogs, the first report based on genome-wide SNPs for Rottweilers, and an almost tenfold improvement in marker density over previous genome-wide studies of LD in Golden Retrievers.}, number={9-10}, journal={MAMMALIAN GENOME}, author={Stern, Joshua A. and White, Stephen N. and Meurs, Kathryn M.}, year={2013}, month={Oct}, pages={409–415} } @article{maran_mealey_lahmers_nelson_meurs_2013, title={Identification of DNA variants in the canine beta-1 adrenergic receptor gene}, volume={95}, ISSN={0034-5288}, url={http://dx.doi.org/10.1016/j.rvsc.2013.02.021}, DOI={10.1016/j.rvsc.2013.02.021}, abstractNote={Beta-adrenergic receptor antagonists are utilized for the management of several cardiac diseases in the dog. In humans the beneficial effects of beta-adrenergic receptor antagonists are variable and are associated with a genetic variability in the beta one adrenergic receptor gene (ADRB1). To determine if DNA variants were present in the canine ADRB1 gene, DNA from five breeds of dogs was evaluated. Two deletions were identified within the region of the gene that encodes the cytoplasmic tail of ADRB1. The functions of this region are not well understood although it is important in differentiating subtypes of adrenergic receptors and may be associated with control of receptor downregulation. The functional consequences of these identified variants deserve further study.}, number={1}, journal={Research in Veterinary Science}, publisher={Elsevier BV}, author={Maran, B.A. and Mealey, K.L. and Lahmers, S.M. and Nelson, O.L. and Meurs, K.M.}, year={2013}, month={Aug}, pages={238–240} } @article{stern_reina-doreste_chdid_meurs_2014, title={Identification of PDE5A:E90K: A Polymorphism in the Canine Phosphodiesterase 5A Gene Affecting Basal cGMP Concentrations of Healthy Dogs}, volume={28}, ISSN={["1939-1676"]}, url={https://europepmc.org/articles/PMC4895552}, DOI={10.1111/jvim.12256}, abstractNote={BackgroundCyclic guanosine monophosphate (cGMP)‐specific phosphodiesterase (PDE5A) is the target of phosphodiesterase inhibitors such as sildenafil. Polymorphisms in the PDE5A gene that may predict response to therapy with sildenafil and nitric oxide, be linked to disease progression, and aid in risk assessment have been identified in human beings. Identification of polymorphisms in PDE5A could affect the physiologic actions of PDE5A and the effects of phosphodiestrase type 5 inhibitor drugs.Hypothesis/ObjectiveFunctional polymorphisms exist in the canine PDE5A gene. Specific objectives were to identify PDE5A polymorphisms and evaluate their functional relevance.AnimalsSeventy healthy dogs.MethodsThe exonic, splice‐site, 3′ and 5′ untranslated regions of the canine PDE5A gene were sequenced in 15 dogs and aligned with the canine reference sequence. Identified polymorphisms were evaluated in 55 additional, healthy, unrelated dogs of 20 breeds. Plasma was collected from 51 of these dogs and cGMP was measured. An unpaired t‐test and one‐way ANOVA with Dunnett's test of multiple comparisons were used to evaluate the effect of genotype on cGMP.ResultsA common exonic polymorphism was identified that changed glutamic acid to lysine and resulted in significantly lower cGMP concentrations in the group with polymorphism versus the wild type group (P = .014). Additionally, 6 linked single nucleotide polymorphisms in the 3′ untranslated region were identified that did not alter cGMP concentrations.Conclusions and Clinical ImportanceA polymorphism exists in the canine PDE5A gene that is associated with variable circulating cGMP concentrations in healthy dogs and warrants investigation in diseases such as pulmonary hypertension.}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Stern, J. A. and Reina-Doreste, Y. and Chdid, L. and Meurs, K. M.}, year={2014}, month={Jan}, pages={78–83} } @article{meurs_lahmers_keene_white_oyama_mauceli_lindblad-toh_2012, title={A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher}, volume={131}, ISSN={["1432-1203"]}, DOI={10.1007/s00439-012-1158-2}, abstractNote={Familial dilated cardiomyopathy is a primary myocardial disease that can result in the development of congestive heart failure and sudden cardiac death. Spontaneous animal models of familial dilated cardiomyopathy exist and the Doberman pinscher dog is one of the most commonly reported canine breeds. The objective of this study was to evaluate familial dilated cardiomyopathy in the Doberman pinscher dog using a genome-wide association study for a genetic alteration(s) associated with the development of this disease in this canine model. Genome-wide association analysis identified an area of statistical significance on canine chromosome 14 (p(raw) = 9.999e-05 corrected for genome-wide significance), fine-mapping of additional SNPs flanking this region localized a signal to 23,774,190-23,781,919 (p = 0.001) and DNA sequencing identified a 16-base pair deletion in the 5' donor splice site of intron 10 of the pyruvate dehydrogenase kinase 4 gene in affected dogs (p < 0.0001). Electron microscopy of myocardium from affected dogs demonstrated disorganization of the Z line, mild to moderate T tubule and sarcoplasmic reticulum dilation, marked pleomorphic mitochondrial alterations with megamitochondria, scattered mitochondria with whorling and vacuolization and mild aggregates of lipofuscin granules. In conclusion, we report the identification of a splice site deletion in the PDK4 gene that is associated with the development of familial dilated cardiomyopathy in the Doberman pinscher dog.}, number={8}, journal={HUMAN GENETICS}, author={Meurs, Kathryn M. and Lahmers, Sunshine and Keene, Bruce W. and White, Stephen N. and Oyama, Mark A. and Mauceli, Evan and Lindblad-Toh, Kerstin}, year={2012}, month={Aug}, pages={1319–1325} } @article{trafny_freeman_bulmer_macgregor_rush_meurs_oyama_2012, title={Auscultatory, echocardiographic, biochemical, nutritional, and environmental characteristics of mitral valve disease in Norfolk terriers}, volume={14}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2011.10.002}, DOI={10.1016/j.jvc.2011.10.002}, abstractNote={{"Label"=>"OBJECTIVES", "NlmCategory"=>"OBJECTIVE"} In order to more fully understand degenerative mitral valve disease (DMVD) in the Norfolk terrier, we sought to characterize findings from the physical and echocardiographic examination; biochemical, biomarker, and nutritional profiles; and select environmental variables from a cohort of apparently healthy Norfolk terriers. {"Label"=>"ANIMALS, MATERIALS AND METHODS", "NlmCategory"=>"METHODS"} Overtly healthy Norfolk terriers ≥ 6 yrs old were recruited by 3 different veterinary hospitals and underwent historical, physical, electrocardiographic (ECG), and 2D/color-flow Doppler echocardiographic examinations. Anterior mitral valve leaflet length, maximal thickness, area, and degree of prolapse were measured or calculated from two-dimensional images. Blood samples were obtained for serum biochemistry, serum serotonin, plasma NT-proBNP, amino acid profile, C-reactive protein, and cardiac troponin I. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} Of the 48 dogs entered into the study, 23 (48%) had murmurs, 2 (4%) had mid-systolic clicks, 11 (23%) had ECG P pulmonale, and 41 (85%) were deemed to have echocardiographic evidence of DMVD, including 18 Norfolk terriers without a murmur. Seven (15%), 28 (58%), and 13 (27%) dogs were classified as normal (stage 0), International Small Animal Cardiac Health Council (ISACHC) stage 1a, and 1b, respectively. Mean indexed echocardiographic mitral leaflet thickness (P = 0.017), area (P = 0.0002), prolapse (P = 0.0004), and left atrial to aortic diameter (P = 0.01) were significantly different between ISACHC 0, 1a, and 1b. {"Label"=>"CONCLUSION", "NlmCategory"=>"CONCLUSIONS"} DMVD is relatively common in Norfolk terriers and echocardiographic changes consistent with mild DMVD can be seen in dogs without a heart murmur.}, number={1}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Trafny, Dennis J. and Freeman, Lisa M. and Bulmer, Barret J. and MacGregor, John M. and Rush, John E. and Meurs, Kathryn M. and Oyama, Mark A.}, year={2012}, month={Mar}, pages={261–267} } @article{freeman_rush_meurs_bulmer_cunningham_2012, title={Body size and metabolic differences in Maine Coon cats with and without hypertrophic cardiomyopathy}, volume={15}, ISSN={1098-612X 1532-2750}, url={http://dx.doi.org/10.1177/1098612x12460847}, DOI={10.1177/1098612x12460847}, abstractNote={ An interplay between growth, glucose regulation and hypertrophic cardiomyopathy (HCM) may exist, but has not been studied in detail. The purpose of this study was to characterize morphometric features, insulin-like growth factor-1 (IGF-1) and glucose metabolism in Maine Coon cats with HCM. Body weight, body condition score (BCS), head length and width, and abdominal circumference were measured in Maine Coon cats >2 years of age. Echocardiography and thoracic radiography (for measurement of humerus length, and fourth and twelfth vertebrae length) were also performed. Blood was collected for biochemistry profile, DNA testing, insulin and IGF-1. Sixteen of 63 cats had HCM [myosin binding protein C (MYBPC)+, n = 3 and MYBPC−, n = 13] and 47/63 were echocardiographically normal (MYBPC+, n = 17 and MYBPC−, n = 30). There were no significant differences in any measured parameter between MYBPC+ and MYBPC− cats. Cats with HCM were significantly older ( P <0.001), heavier ( P = 0.006), more obese ( P = 0.008), and had longer humeri ( P = 0.02) compared with the HCM− group. Cats with HCM also had higher serum glucose ( P = 0.01), homeostasis model assessment (HOMA) and IGF-1 ( P = 0.01) concentrations, were from smaller litters ( P = 0.04), and were larger at 6 months ( P = 0.02) and at 1 year of age ( P = 0.03). Multivariate analysis revealed that age ( P <0.001), BCS ( P = 0.03) and HOMA ( P = 0.047) remained significantly associated with HCM. These results support the hypothesis that early growth and nutrition, larger body size and obesity may be environmental modifiers of genetic predisposition to HCM. Further studies are warranted to evaluate the effects of early nutrition on the phenotypic expression of HCM. }, number={2}, journal={Journal of Feline Medicine and Surgery}, publisher={SAGE Publications}, author={Freeman, Lisa M and Rush, John E and Meurs, Kathryn M and Bulmer, Barret J and Cunningham, Suzanne M}, year={2012}, month={Sep}, pages={74–80} } @article{stern_meurs_nelson_lahmers_lehmkuhl_2012, title={Familial subvalvular aortic stenosis in golden retrievers: inheritance and echocardiographic findings}, volume={53}, ISSN={0022-4510}, url={http://dx.doi.org/10.1111/j.1748-5827.2011.01187.x}, DOI={10.1111/j.1748-5827.2011.01187.x}, abstractNote={Objectives: To describe the echocardiographic findings and pedigree analysis of golden retrievers with subvalvular aortic stenosis.Methods: Seventy‐three golden retrievers were evaluated by auscultation and echocardiography. A subcostal continuous‐wave Doppler aortic velocity ê2·5 m/s and presence of a left basilar systolic ejection murmur were required for diagnosis of subvalvular aortic stenosis. Three echocardiographic characteristics were recorded: evidence of aortic insufficiency, subvalvular ridge or left ventricular hypertrophy. A disease status score was calculated by totalling the number of echocardiographic ‐characteristics per subject.Results: Thirty‐two of 73 dogs were affected and their aortic velocities were as follows: range 2·5 to 6·8 m/s, median 3·4 m/s and standard deviation 1·2 m/s. Echocardiographic characteristics of 32 affected dogs were distributed as follows: left ventricular hypertrophy 12 of 32, aortic insufficiency 20 of 32 and subvalvular ridge 20 of 32. Disease status score ranged from 0 to 3 with a median of 2. There was a statistically significant correlation between aortic velocity and disease status score (r=0·644, P<0·0001). Subvalvular aortic stenosis was observed in multiple generations of several families and appears familial.Clinical Significance: Subvalvular aortic stenosis in the golden retriever is familial. Severity of stenosis correlates well with cumulative presence of echocardiographic characteristics (left ventricular hypertrophy, subvalvular ridge and aortic insufficiency).}, number={4}, journal={Journal of Small Animal Practice}, publisher={Wiley}, author={Stern, J. A. and Meurs, K. M. and Nelson, O. L. and Lahmers, S. M. and Lehmkuhl, L. B.}, year={2012}, month={Mar}, pages={213–216} } @article{silverman_stern_meurs_2012, title={Hypertrophic cardiomyopathy in the Sphynx cat: A retrospective evaluation of clinical presentation and heritable etiology}, volume={14}, ISSN={["1532-2750"]}, url={https://doi.org/10.1177/1098612X11435040}, DOI={10.1177/1098612x11435040}, abstractNote={Hypertrophic cardiomyopathy is an inherited disease in some feline breeds including the Maine Coon and Ragdoll. In these breeds, distinct causative genetic mutations have been identified. The two breeds appear to have slightly different clinical presentations, including age of diagnosis. The observation that these two breeds may have different clinical presentations, as well as different genetic mutations, suggests that hypertrophic cardiomyopathy is a diverse disease in the cat. Hypertrophic cardiomyopathy is poorly described in the Sphynx. The objective of this study was to phenotypically characterize Sphynx hypertrophic cardiomyopathy and to evaluate for a familial etiology. Records of 18 affected cats (11 female, seven male) were evaluated. Age of affected cats ranged from 0.5 to 7 years (median, 2 years). Four affected cats were from a single family and included an affected cat in each of four generations (three females, one male). Further studies are warranted to evaluate for a causative mutation and better classify the phenotypic expression.}, number={4}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Silverman, Sarah J. and Stern, Joshua A. and Meurs, Kathryn M.}, year={2012}, month={Apr}, pages={246–249} } @article{meurs_heaney_atkins_defrancesco_fox_keene_kellihan_miller_oyama_oaks_et al._2011, title={Comparison of Polymerase Chain Reaction with Bacterial 16s Primers to Blood Culture to Identify Bacteremia in Dogs with Suspected Bacterial Endocarditis}, volume={25}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/j.1939-1676.2011.0742.x}, DOI={10.1111/j.1939-1676.2011.0742.x}, abstractNote={Background: Identification of the bacterial organism in dogs with endocarditis is challenging. Human studies have reported the utility of the polymerase chain reaction (PCR) to amplify and identify bacterial nucleic acid from infected valvular tissue and blood.Hypothesis/Objectives: We hypothesized that PCR using primers designed to amplify the bacterial 16s gene would identify circulating bacteria in dogs with suspected bacterial endocarditis more consistently than standard blood culture techniques.Animals: Eighteen dogs with suspected bacterial endocarditis based upon clinical and echocardiographic findings. Fifteen clinically normal dogs served as negative controls.Methods: Prospective study of dogs evaluated for suspect endocarditis at 6 veterinary hospitals. A blood sample was drawn from all dogs and evaluated with both a single‐sample PCR and standard 3‐sample blood culture techniques.Results: Blood culture identified noncontaminant bacteria in 6/18 study animals (33%) and 1 control dog; PCR identified noncontaminant bacteria in 7/18 study animals (39%). There were no study animals in which the 2 tests identified different bacteria (κ= 1.0). However, bacteria were identified by both techniques in only 2/18 study animals. When results from both PCR and blood culture were considered together, a noncontaminant bacterial organism was identified in 11/18 study animals (61%).Conclusion and Clinical Importance: The results of this study suggest that although single sample PCR with 16s primers was not more sensitive than blood culture for detection of bacteremia in dogs with suspect endocarditis, performing both techniques simultaneously did increase the likelihood of identification of bacteria in blood.}, number={4}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Meurs, K.M. and Heaney, A.M. and Atkins, C.E. and DeFrancesco, T.C. and Fox, P.R. and Keene, B.W. and Kellihan, H.B. and Miller, M.W. and Oyama, M.A. and Oaks, J.L. and et al.}, year={2011}, month={Jun}, pages={959–962} } @article{maran_meurs_lahmers_nelson_2012, title={Identification of beta-1 adrenergic receptor polymorphisms in cats}, volume={93}, ISSN={0034-5288}, url={http://dx.doi.org/10.1016/j.rvsc.2011.05.007}, DOI={10.1016/j.rvsc.2011.05.007}, abstractNote={In human beings, genetic polymorphisms within the beta-1 adrenergic receptor (ADRB1) gene have been associated with variable pharmacologic responses to beta blocker therapy. Beta-blockers are commonly given to cats with heart disease, particularly hypertrophic cardiomyopathy, a common cause of feline heart disease. We hypothesized that polymorphisms are present in the feline ADRB1 gene, which could result in an altered pharmacologic response to beta-blocker therapy. We sequenced the feline ADRB1 gene in 42 cats of five breeds. We identified three polymorphisms within the ADRB1 gene. Two polymorphisms did not change the amino acid produced and are unlikely to be clinically significant. A third polymorphism identified was an AA/CC substitution at the 830-831 base pair sites. This alteration changed the amino acid produced from proline to glutamine at position 277 and computer modeling predicts an altered protein structure. Further study is warranted to determine if this polymorphism alters response to beta blocker therapy.}, number={1}, journal={Research in Veterinary Science}, publisher={Elsevier BV}, author={Maran, B.A. and Meurs, K.M. and Lahmers, S.M. and Nelson, O.L.}, year={2012}, month={Aug}, pages={210–212} } @article{stern_meurs_spier_koplitz_baumwart_2010, title={Ambulatory electrocardiographic evaluation of clinically normal adult Boxers}, volume={236}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.236.4.430}, DOI={10.2460/javma.236.4.430}, abstractNote={Abstract Objective—To determine the prevalence of ventricular arrhythmias in clinically normal adult Boxers. Design—Prospective cross-sectional study. Animals—301 Boxers (181 females and 120 males) > 1 year old with echocardiographically normal systolic function and no history of syncope or congestive heart failure. Procedures—Physical examination, which included echocardiography, was performed on all dogs. A 24-hour ambulatory ECG was performed on each dog, and results were evaluated to assess ventricular arrhythmias. Statistical evaluation was performed to determine correlations between the total number of ventricular premature complexes (VPCs)/24 h, grade of ventricular arrhythmia, and age of the dogs. Results—Age of dogs ranged from 1 to 16 years (median, 4 years). Number of VPCs/24 h in each dog ranged from 0 to 62,622 (median, 6 VPCs/24 h). Grade of arrhythmias ranged from 0 to 3 (median, 1). Age was correlated significantly with number of VPCs/24 h (r = 0.43) and with grade of arrhythmia (r = 0.37). Number of VPCs/24 h was significantly correlated with grade of arrhythmia (r = 0.82). Conclusions and Clinical Relevance—Clinically normal adult Boxers generally had < 91 VPCs/24 h and an arrhythmia grade < 2. Boxers with > 91 VPCs/24 h were uncommon and may have represented dogs with arrhythmogenic right ventricular cardiomyopathy or other disease processes that could have resulted in the development of ventricular arrhythmias.}, number={4}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Stern, Joshua A. and Meurs, Kathryn M. and Spier, Alan W. and Koplitz, Shianne L. and Baumwart, Ryan D.}, year={2010}, month={Feb}, pages={430–433} } @article{lamb_meurs_hamlin_2010, title={Correlation of heart rate to body weight in apparently normal dogs}, volume={12}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2010.04.001}, DOI={10.1016/j.jvc.2010.04.001}, abstractNote={{"Label"=>"OBJECTIVE", "NlmCategory"=>"OBJECTIVE"} To evaluate the correlation between heart rate and body weight in the apparently healthy dog. {"Label"=>"ANIMALS", "NlmCategory"=>"METHODS"} Sixty dogs weighing between 2 and 80 kg. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} Heart rate was evaluated with a 24-h ambulatory electrocardiogram. Minimum, average, maximum heart rate, ventricular premature complex (VPC) number and supraventricular premature complex (SVC) number were tabulated for each dog. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} Minimum, maximum and average heart rate did not correlate to body weight. For all dogs, the median minimum heart rate was 42 bpm (beats per minute), median average heart rate was 73 bpm, and median maximum heart rate was 190. The median number of VPCs and SVC was zero. {"Label"=>"CONCLUSIONS", "NlmCategory"=>"CONCLUSIONS"} The present study does not support a correlation between heart rate and body weight in apparently healthy dogs.}, number={2}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Lamb, Allison P. and Meurs, Kathryn M. and Hamlin, Robert L.}, year={2010}, month={Aug}, pages={107–110} } @article{meurs_kuan_2010, title={Differential methylation of CpG sites in two isoforms of myosin binding protein C, an important hypertrophic cardiomyopathy gene}, volume={52}, ISSN={0893-6692}, url={http://dx.doi.org/10.1002/em.20596}, DOI={10.1002/em.20596}, abstractNote={AbstractHypertrophic cardiomyopathy (HCM) is a common form of cardiac disease. Over 400 causative mutations have been identified in 20 sarcomere and myofilament related genes. The high density of mutations found in genes associated with HCM may suggest that mechanisms promoting increased mutability play a role in disease prevalence. The objective of this study was to evaluate the CpG methylation level of the exonic regions of the cardiac myosin binding protein C gene (MYBPC3), a common causal gene for HCM. To determine if the methylation level is gene specific and possibly involved with gene mutability, we also evaluated the methylation of the CpGs within the exonic regions of the skeletal muscle isoform of the myosin binding protein C gene (MYBPC2); there are no known mutations that lead to the development of familial human disease within this gene. We determined that although the mean number of CG sites was identical within the coding region of each gene, the mean methylation level of CpGs was significantly higher in MYBPC3 than MYBPC2 (P < 0.0001). The results of this study suggest that there are unique aspects of this cardiac gene or its epigenetic environment which may result in increased genetic mutability. Evaluation of the methylation levels of additional causal cardiomyopathic genes is warranted. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.}, number={2}, journal={Environmental and Molecular Mutagenesis}, publisher={Wiley}, author={Meurs, Kathryn M. and Kuan, Mani}, year={2010}, month={Aug}, pages={161–164} } @inbook{meurs_2010, place={Philadelphia}, title={Genetic screening of familial hypertrophic cardiomyopathy}, booktitle={Consultations in Feline Internal Medicine}, publisher={WB Saunders}, author={Meurs, K.M.}, year={2010}, pages={406–408} } @article{meurs_2010, title={Genetics of Cardiac Disease in the Small Animal Patient}, volume={40}, ISSN={0195-5616}, url={http://dx.doi.org/10.1016/j.cvsm.2010.03.006}, DOI={10.1016/j.cvsm.2010.03.006}, abstractNote={There is increasing evidence that many forms of congenital and acquired cardiovascular disease in small animal patients are of familial origin. The large number of familial diseases in domestic purebred animals is thought to be associated with the desire to breed related animals to maintain a specific appearance and the selection of animals from a small group of popular founders (founder effect). Clinicians can use knowledge that a particular trait or disease may be inherited to provide guidance to owners and animal breeders to reduce the frequency of the trait. Even if the molecular cause is not known, identification of a pattern of inheritance and information on clinical screening can be useful for a breeder trying to make breeding decisions. Common forms of inheritance for veterinary diseases include autosomal recessive, autosomal dominant, X-linked recessive, and polygenic. These genetic traits and their possible involvement in cardiac disease in small animals are discussed in this article.}, number={4}, journal={Veterinary Clinics of North America: Small Animal Practice}, publisher={Elsevier BV}, author={Meurs, Kathryn M.}, year={2010}, month={Jul}, pages={701–715} } @article{meurs_mauceli_lahmers_acland_white_lindblad-toh_2010, title={Genome-wide association identifies a deletion in the 3′ untranslated region of Striatin in a canine model of arrhythmogenic right ventricular cardiomyopathy}, volume={128}, ISSN={0340-6717 1432-1203}, url={http://dx.doi.org/10.1007/s00439-010-0855-y}, DOI={10.1007/s00439-010-0855-y}, abstractNote={Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiac disease characterized by ventricular arrhythmias and sudden cardiac death. It is most frequently inherited as an autosomal dominant trait with incomplete and age-related penetrance and variable clinical expression. The human disease is most commonly associated with a causative mutation in one of several genes encoding desmosomal proteins. We have previously described a spontaneous canine model of ARVC in the boxer dog. We phenotyped adult boxer dogs for ARVC by performing physical examination, echocardiogram and ambulatory electrocardiogram. Genome-wide association using the canine 50k SNP array identified several regions of association, of which the strongest resided on chromosome 17. Fine mapping and direct DNA sequencing identified an 8-bp deletion in the 3′ untranslated region (UTR) of the Striatin gene on chromosome 17 in association with ARVC in the boxer dog. Evaluation of the secondary structure of the 3′ UTR demonstrated that the deletion affects a stem loop structure of the mRNA and expression analysis identified a reduction in Striatin mRNA. Dogs that were homozygous for the deletion had a more severe form of disease based on a significantly higher number of ventricular premature complexes. Immunofluorescence studies localized Striatin to the intercalated disc region of the cardiac myocyte and co-localized it to three desmosomal proteins, Plakophilin-2, Plakoglobin and Desmoplakin, all involved in the pathogenesis of ARVC in human beings. We suggest that Striatin may serve as a novel candidate gene for human ARVC.}, number={3}, journal={Human Genetics}, publisher={Springer Science and Business Media LLC}, author={Meurs, Kathryn M. and Mauceli, Evan and Lahmers, Sunshine and Acland, Gregory M. and White, Stephen N. and Lindblad-Toh, Kerstin}, year={2010}, month={Jul}, pages={315–324} } @inbook{meurs_2010, place={Philadelphia}, edition={7th}, title={Primary myocardial disease in the dog}, booktitle={Textbook of Veterinary Internal Medicine}, publisher={WB Saunders}, author={Meurs, K.M.}, year={2010}, pages={1320–1328} } @article{craven_acland_mezey_boyko_wang_meurs_mcdonough_simpson_2010, title={W1250 Genome-Wide Association Scan Reveals Polymorphisms in the P67phox Subunit (Ncf2) of the NADPH Oxidase Complex in Boxer Dogs With Adherent and Invasive E.Coli-Associated Granulomatous Colitis: A Potential Model of Chronic Granulomatous Disease}, volume={138}, ISSN={0016-5085}, url={http://dx.doi.org/10.1016/S0016-5085(10)63141-1}, DOI={10.1016/S0016-5085(10)63141-1}, abstractNote={within the same year.Six of ten CD pairs shared similar smoking history (4 smokers, 2 exsmokers), and 6 of nine pairs were concordant for severity of disease.Of the five dizygotic twins with CD, disease location and behaviour were also identical in all twin pairs.In nine monozygotic twins with UC (4 females; 5 males), there was good agreement for the use of thiopurine (kappa 0.73; 95%CI 0.10, 1.00) and disease extent (5 total colitis; 1 distal colitis; 1 proctitis) (κappa 0.60; 95% CI 0.13, 1.00).Agreement was poor for disease severity, smoking status, need for steroids and extraintestinal symptoms in UC twins.UC twins were diagnosed at (mean±SEM) 5±1 years of each other.There was no concordance for colectomy in UC twins (2 patients out of 9 UC twin pairs).The majority of concordant IBD twins shared same bedrooms and attended the same school up to a median age of 17 years (range 9-24).CONCLUSION: Our findings suggest that age of disease onset, disease location and disease behaviour in CD, and disease extent in UC, but not extraintestinal manifestations, appeared to be strongly genetically-influenced.}, number={5}, journal={Gastroenterology}, publisher={Elsevier BV}, author={Craven, Melanie and Acland, Gregory M. and Mezey, Jason and Boyko, Adam and Wang, Wei and Meurs, Kathryn and McDonough, Sean and Simpson, Kenneth W.}, year={2010}, month={May}, pages={S-683} } @inbook{meurs_2009, title={Acquired Heart Diseases in Cattle}, ISBN={9781416035916}, url={http://dx.doi.org/10.1016/b978-141603591-6.10050-8}, DOI={10.1016/b978-141603591-6.10050-8}, booktitle={Food Animal Practice}, publisher={Elsevier}, author={Meurs, Kathryn M.}, year={2009}, pages={216–219} } @article{meurs_norgard_kuan_haggstrom_kittleson_2009, title={Analysis of 8 Sarcomeric Candidate Genes for Feline Hypertrophic Cardiomyopathy Mutations in Cats with Hypertrophic Cardiomyopathy}, volume={23}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.2009.0341.x}, DOI={10.1111/j.1939-1676.2009.0341.x}, abstractNote={Background: Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats. Causative mutations have been identified in the Maine Coon (MC) and Ragdoll breed in the cardiac myosin binding protein C gene (MYBPC3). HCM is thought to be inherited in other breeds.Hypothesis: That a causative mutation for HCM in the British Shorthair (BSH), Norwegian Forest (NWF), Siberian, Sphynx, or MC cats would be identified in the exonic and splice site regions of 1 of 8 genes associated with human familial HCM.Animals: Three affected BSH, NWF, Siberians, Sphynx, 2 MC (without the known MC mutation), and 2 Domestic Shorthair cats (controls) were studied.Methods: Prospective, observational study. Exonic and splice site regions of the genes encoding the proteins cardiac troponin I, troponin T, MYBPC3, cardiac essential myosin light chain, cardiac regulatory myosin light chain, α tropomyosin, actin, and β–myosin heavy chain were sequenced. Sequences were compared for nucleotide changes between affected cats, the published DNA sequences, and control cats. Changes were considered to be causative for HCM if they involved a conserved amino acid and changed the amino acid to a different polarity, acid‐base status, or structure.Results: A causative mutation for HCM was not identified, although several single nucleotide polymorphisms were detected.Conclusions and Clinical Importance: Mutations within these cardiac genes do not appear to be the only cause of HCM in these breeds. Evaluation of additional cardiac genes is warranted to identify additional molecular causes of this feline cardiac disease.}, number={4}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Meurs, K.M. and Norgard, M.M. and Kuan, M. and Haggstrom, J. and Kittleson, M.}, year={2009}, month={Jul}, pages={840–843} } @inbook{meurs_spier_2009, place={Philadelphia}, title={Cardiomyopathy in the boxer dog}, booktitle={Current Veterinary Therapy (Small Animal Practice) XIV}, publisher={WB Saunders}, author={Meurs, K.M. and Spier, A.W.}, year={2009}, pages={797–799} } @inbook{meurs_2009, title={Congenital Heart Disease in Cattle}, ISBN={9781416035916}, url={http://dx.doi.org/10.1016/b978-141603591-6.10049-1}, DOI={10.1016/b978-141603591-6.10049-1}, booktitle={Food Animal Practice}, publisher={Elsevier}, author={Meurs, Kathryn M.}, year={2009}, pages={215–216} } @inbook{meurs_2009, title={Examination of the Bovine Patient with Heart Disease}, ISBN={9781416035916}, url={http://dx.doi.org/10.1016/b978-141603591-6.10048-x}, DOI={10.1016/b978-141603591-6.10048-x}, booktitle={Food Animal Practice}, publisher={Elsevier}, author={Meurs, Kathryn M.}, year={2009}, pages={214–215} } @article{baumwart_meurs_raman_2009, title={Magnetic Resonance Imaging of Right Ventricular Morphology and Function in Boxer Dogs with Arrhythmogenic Right Ventricular Cardiomyopathy}, volume={23}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.2008.0266.x}, DOI={10.1111/j.1939-1676.2008.0266.x}, abstractNote={Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a myocardial disease characterized by fibrofatty replacement of the right ventricle and ventricular tachyarrhythmias, reported most commonly in the Boxer dog. Although ARVC is characterized as a myocardial disease, the impact of the disease on the function of the right ventricle has not been well studied.Objective: To noninvasively evaluate the function and anatomy of the right ventricle in Boxer dogs with ARVC.Animals: Five adult Boxer dogs with ARVC and 5 healthy size‐matched hound dogs.Methods: Magnetic resonance imaging was performed on an ECG‐gated conventional 1.5‐T scanner using dark blood imaging and cine acquisitions. Images were evaluated by delineation of endocardial right and left ventricular contours in the end‐diastolic and end‐systolic phases of each slice. Right and left end‐systolic and end‐diastolic volumes were generated using Simpson's rule and ejection fraction was calculated. Images were evaluated for right ventricular (RV) aneurysms and wall motion abnormalities. Spin echo images were reviewed for the presence of RV myocardial fatty replacement or scar.Results: RV ejection fraction was significantly lower in Boxers with ARVC compared with the controls (ARVC 34%± 11 control 53%± 10, P < .01). There was an RV aneurysm in 1 dog with ARVC but not in any of the controls. RV myocardial gross fatty changes were not observed in dogs of either group.Conclusions and Clinical Importance: These findings could be interpreted to suggest that arrhythmias and myocardial dysfunction precede the development of morphological abnormalities in dogs with ARVC.}, number={2}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Baumwart, R.D. and Meurs, K.M. and Raman, S.V.}, year={2009}, month={Mar}, pages={271–274} } @article{scansen_meurs_spier_koplitz_baumwart_2009, title={Temporal Variability of Ventricular Arrhythmias in Boxer Dogs with Arrhythmogenic Right Ventricular Cardiomyopathy}, volume={23}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.2009.0366.x}, DOI={10.1111/j.1939-1676.2009.0366.x}, abstractNote={Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is prevalent in the Boxer. There is little information on the temporal variability of ventricular arrhythmias within affected dogs.Objective: To evaluate ambulatory electrocardiograms (AECG) from Boxers with ARVC for hourly variation in premature ventricular complexes (PVC) and heart rate (HR).Animals: One hundred and sixty‐two Boxer dogs with ARVC.Methods: Retrospective, observational study of 1,181 AECGs collected from Boxer dogs at The Ohio State University from 1997 to 2004 was evaluated. The proportion of depolarizations that were PVCs was compared across each hour of the day, during six 4‐hour periods of day, to the time after AECG application, and to the maximum and minimum HR.Results: A lower proportion of PVCs was noted during early morning (midnight to 0400 hours) as compared with the morning (0800–1200 hours) and late (1600–2000 hours) afternoon (P= .012). There was no increase in PVC proportion in the 1st hour after AECG application as compared with all other hours of the day (P= .06). There was poor correlation between maximum (ρ= 0.19) and minimum (ρ= 0.12) HR and PVC proportion.Conclusions and Clinical Importance: The likelihood of PVC occurrence in Boxer dogs with ARVC was relatively constant throughout the day, although slightly greater during the hours of 0800–1200 and 1600–2000. A biologically important correlation with HR was not apparent. The role of autonomic activity in the modulation of electrical instability in the Boxer with ARVC requires further study.}, number={5}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Scansen, B.A. and Meurs, K.M. and Spier, A.W. and Koplitz, S. and Baumwart, R.D.}, year={2009}, month={Sep}, pages={1020–1024} } @inbook{calvert_meurs_2009, place={Philadelphia}, title={Update on Doberman pinscher cardiomyopathy}, booktitle={Current Veterinary Therapy (Small Animal Practice) XIV}, publisher={WB Saunders}, author={Calvert, C. and Meurs, K.M.}, year={2009}, pages={800–803} } @article{baumwart_meurs_2008, title={An index of myocardial performance applied to the right ventricle of Boxers with arrhythmogenic right ventricular cardiomyopathy}, volume={69}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.69.8.1029}, DOI={10.2460/ajvr.69.8.1029}, abstractNote={Abstract Objective—To use an index of myocardial performance (IMP) to assess right ventricular function in Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC). Animals—22 Boxers (12 Boxers with ARVC diagnosed by the detection of ≥ 1,000 ventricular premature complexes (VPCs)/24 h and 10 Boxers with ≤ 5 VPCs/24 h (control dogs). Procedures—Pulsed-wave Doppler recordings of tricuspid inflow and pulmonic outflow were acquired. Preejection period (PEP), ejection time (ET), PEP/ET, and IMP were determined for the right ventricle by use of data from separate cardiac cycles. Results—A significant difference was not identified between groups for right ventricular PEP, right ventricular ET, right ventricular PEP/ET, or right ventricular IMP. Right ventricular IMP was not significantly correlated with VPC number (r = 0.21) or VPC grade (r = −0.3) in Boxers with ARVC. Conclusions and Clinical Relevance—Boxers with ARVC did not have significant differences in right ventricular IMP, compared with results for control Boxers. This would suggest that right ventricular dysfunction does not develop in Boxers with ARVC or that a more severe phenotype of the disease may be necessary for detection of dysfunction. Additional studies that use more sensitive techniques to evaluate myocardial function may be warranted.}, number={8}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Baumwart, Ryan D. and Meurs, Kathryn M.}, year={2008}, month={Aug}, pages={1029–1033} } @article{oyama_reiken_lehnart_chittur_meurs_stern_marks_2008, title={Arrhythmogenic right ventricular cardiomyopathy in Boxer dogs is associated with calstabin2 deficiency}, volume={10}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2008.04.003}, DOI={10.1016/j.jvc.2008.04.003}, abstractNote={To examine the presence and effect of calstabin2-deficiency in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC). Thirteen Boxer dogs with ARVC. Tissue samples were collected for histopathology, oligonucleotide microarray, PCR, immunoelectrophoresis, ryanodine channel immunoprecipitation and single-channel recordings, and calstabin2 DNA sequencing. In cardiomyopathic Boxer dogs, myocardial calstabin2 mRNA and protein were significantly decreased as compared to healthy control dogs (calstabin2 protein normalized to tetrameric cardiac ryanodine receptor (RyR2) complex: affected, 0.51 ± 0.04; control, 3.81 ± 0.22; P < 0.0001). Calstabin2 deficiency in diseased dog hearts was associated with a significantly increased open probability of single RyR2 channels indicating intracellular Ca2+ leak. PCR-based sequencing of the promoter, exonic and splice site regions of the canine calstabin2 gene did not identify any causative mutations. Calstabin2 deficiency is a potential mechanism of Ca2+ leak-induced ventricular arrhythmias and heart disease in Boxer dogs with ARVC.}, number={1}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Oyama, Mark A. and Reiken, Steve and Lehnart, Stephan E. and Chittur, Sridar V. and Meurs, Kathryn M. and Stern, Joshua and Marks, Andrew R.}, year={2008}, month={Jun}, pages={1–10} } @article{mealey_meurs_2008, title={Breed distribution of the ABCB1-1Δ (multidrug sensitivity) polymorphism among dogs undergoing ABCB1 genotyping}, volume={233}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.233.6.921}, DOI={10.2460/javma.233.6.921}, abstractNote={Abstract Objective—To evaluate the breed distribution of the ABCB1-1Δ polymorphism in a large number of dogs in North America, including dogs of several herding breeds in which this polymorphism has been detected and other breeds in which this polymorphism has not yet been identified. Design—Cross-sectional study. Animals—5,368 dogs from which buccal swab samples were collected for purposes of ABCB1 genotyping. Procedures—From May 1, 2004, to September 30, 2007, DNA specimens derived from buccal swab samples collected from 5,368 dogs underwent ABCB1 genotyping. These data were reviewed, and results for each dog were recorded in a spreadsheet, along with the dog's breed. The genotypes for each breed were tallied by use of a sorting function. Results—The ABCB1-1Δ allele was identified in 9 breeds of dogs and in many mixed-breed dogs. Breeds that had the ABCB1-1Δ allele included Collie, Longhaired Whippet, Australian Shepherd (standard and miniature), Shetland Sheepdog, Old English Sheepdog, Border Collie, Silken Windhound, and German Shepherd Dog (a breed in which this mutation had not been detected previously). Conclusions and Clinical Relevance—The ABCB1-1Δ polymorphism is associated with increased susceptibility to many adverse drug reactions and with suppression of the hypothalamic-pituitary-adrenal axis and is present in many herding breeds of dog. Veterinarians should be familiar with the breeds that have the ABCB1-1Δ polymorphism to make appropriate pharmacologic choices for these patients.}, number={6}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Mealey, Katrina L. and Meurs, Kathryn M.}, year={2008}, month={Sep}, pages={921–924} } @article{meurs_mealey_2008, title={Evaluation of the flanking nucleotide sequences of sarcomeric hypertrophic cardiomyopathy substitution mutations}, volume={642}, ISSN={0027-5107}, url={http://dx.doi.org/10.1016/j.mrfmmm.2008.04.005}, DOI={10.1016/j.mrfmmm.2008.04.005}, abstractNote={Hypertrophic cardiomyopathy (HCM) is a familial myocardial disease with a prevalence of 1 in 500. More than 400 causative mutations have been identified in 13 sarcomeric and myofilament related genes, 350 of these are substitution mutations within eight sarcomeric genes. Within a population, examples of recurring identical disease causing mutations that appear to have arisen independently have been noted as well as those that appear to have been inherited from a common ancestor. The large number of novel HCM mutations could suggest a mechanism of increased mutability within the sarcomeric genes. The objective of this study was to evaluate the most commonly reported HCM genes, beta myosin heavy chain (MYH7), myosin binding protein C, troponin I, troponin T, cardiac regulatory myosin light chain, cardiac essential myosin light chain, alpha tropomyosin and cardiac alpha-actin for sequence patterns surrounding the substitution mutations that may suggest a mechanism of increased mutability. The mutations as well as the 10 flanking nucleotides were evaluated for frequency of di-, tri- and tetranucleotides containing the mutation as well as for the presence of certain tri- and tetranculeotide motifs. The most common substitutions were guanine (G) to adenine (A) and cytosine (C) to thymidine (T). The CG dinucleotide had a significantly higher relative mutability than any other dinucleotide (p<0.05). The relative mutability of each possible trinucleotide and tetranucleotide sequence containing the mutation was calculated; none were at a statistically higher frequency than the others. The large number of G to A and C to T mutations as well as the relative mutability of CG may suggest that deamination of methylated CpG is an important mechanism for mutation development in at least some of these cardiac genes.}, number={1-2}, journal={Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis}, publisher={Elsevier BV}, author={Meurs, Kathryn M. and Mealey, Katrina L.}, year={2008}, month={Jul}, pages={86–89} } @article{meurs_hendrix_norgard_2008, title={Molecular evaluation of five cardiac genes in Doberman Pinschers with dilated cardiomyopathy}, volume={69}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.69.8.1050}, DOI={10.2460/ajvr.69.8.1050}, abstractNote={Abstract Objective—To sequence the exonic and splice site regions of 5 cardiac genes associated with the human form of familial dilated cardiomyopathy (DCM) in Doberman Pinschers with DCM and to identify a causative mutation. Animals—5 unrelated Doberman Pinschers with DCM and 2 unaffected Labrador Retrievers (control dogs). Procedures—Exonic and splice site regions of the 5 genes encoding the cardiac proteins troponin C, lamin A/C, cysteine- and glycine-rich protein 3, cardiac troponin T, and the β-myosin heavy chain were sequenced. Sequences were compared for nucleotide changes between affected dogs and the published canine sequences and 2 control dogs. Base pair changes were considered to be causative for DCM if they were present in an affected dog but not in the control dogs or published sequences and if they involved a conserved amino acid and changed that amino acid to a different polarity, acid-base status, or structure. Results—A causative mutation for DCM in Doberman Pinschers was not identified, although single nucleotide polymorphisms were detected in some dogs in the cysteine- and glycine-rich protein 3, β-myosin heavy chain, and troponin T genes. Conclusions and Clinical Relevance—Mutations in 5 of the cardiac genes associated with the development of DCM in humans did not appear to be causative for DCM in Doberman Pinschers. Continued evaluation of additional candidate genes or a focused approach with an association analysis is warranted to elucidate the molecular cause of this important cardiac disease in Doberman Pinschers.}, number={8}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Meurs, Kathryn M. and Hendrix, Kristina P. and Norgard, Michelle M.}, year={2008}, month={Aug}, pages={1050–1053} } @article{smith_freeman_meurs_rush_lamb_2008, title={Plasma fatty acid concentrations in Boxers and Doberman Pinschers}, volume={69}, DOI={10.2460/ajvr.69.2.195}, abstractNote={Abstract Objective—To compare plasma fatty acid concentrations and the relationships of fatty acids to arrhythmias in Boxers versus Doberman Pinschers. Animals—38 Boxers and 13 Doberman Pinschers. Procedures—Boxers and Doberman Pinschers evaluated via Holter recording and for which a blood sample was available were included. Echocardiograms were performed in 49 of 51 dogs. The number of ventricular premature complexes (VPCs)/24 h was counted and fatty acids analyzed. Plasma fatty acid concentrations and VPCs/24 h, as well as correlations between the 2 variables, were compared between the 2 breeds. Results—Compared with the Doberman Pinschers, Boxers had significantly higher plasma concentrations of γ-linolenic acid but lower concentrations of arachidonic acid. Total n-6 fatty acids and total polyunsaturated fatty acid concentrations were higher in Doberman Pinschers. There were significant, but weak, positive correlations between VPCs and oleic acid, total n-3 fatty acids, and total n-9 fatty acids in Boxers but not in Doberman Pinschers. Conclusions and Clinical Relevance—Data suggested that plasma fatty acid concentrations may differ between Boxers and Doberman Pinschers and that the relationship between fatty acid concentrations and VPCs may be different between these 2 breeds.}, number={2}, journal={American Journal of Veterinary Research}, author={Smith, C.E. and Freeman, L.M. and Meurs, K.M. and Rush, J.E. and Lamb, A.}, year={2008}, pages={195–198} } @article{fries_heaney_meurs_2008, title={Prevalence of the Myosin-Binding Protein C Mutation in Maine Coon Cats}, volume={22}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.2008.0113.x}, DOI={10.1111/j.1939-1676.2008.0113.x}, abstractNote={Background: An autosomal dominant mutation has been identified in the myosin‐binding protein C (MYBPC3) gene of Maine Coon cats. This mutation changes a conserved amino acid and computationally alters the protein conformation of this gene in Maine Coon cats with hypertrophic cardiomyopathy. The prevalence of this mutation is unknown.Objective: To determine the genetic prevalence of the MYBPC3 mutation in a large cohort of predominantly Maine Coon cats.Animals: Three thousand three hundred and ten DNA samples (blood or buccal swab) from cats.Methods: This retrospective study reviewed the Veterinary Cardiac Genetics Laboratory database at Washington State University for samples submitted for evaluation of the Maine Coon MYBPC3 mutation. The data were analyzed with respect to the breed of cat, mutation status (negative, heterozygous, homozygous), and geographic origin of the submission.Results: In the population of cats studied, Maine Coon cats accounted for 100% of all cats positive for the mutation, and the worldwide percentage of Maine Coon cats carrying the MYBPC3 mutation was 34%.Conclusions and Clinical Importance: The prevalence of the mutation (heterozygous or homozygous) was very similar among countries of submission, suggesting that the 34% mutation rate of the tested samples is a reasonable estimate of the true prevalence of the mutation within the breed. Because of the high prevalence of this mutation, a breeding recommendation to eliminate all cats with the mutation could have a substantial impact on the gene pool. Additional studies are indicated to explore the relationship between genotype and clinical outcome in affected cats.}, number={4}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Fries, R. and Heaney, A.M. and Meurs, K.M.}, year={2008}, month={Jul}, pages={893–896} } @article{meurs_fox_norgard_spier_lamb_koplitz_baumwart_2007, title={A Prospective Genetic Evaluation of Familial Dilated Cardiomyopathy in the Doberman Pinscher}, volume={21}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.2007.tb03058.x}, DOI={10.1111/j.1939-1676.2007.tb03058.x}, abstractNote={ Background: The Doberman Pinscher is one of the most common breeds of dogs to develop dilated cardiomyopathy (DCM), a primary heart muscle disorder characterized by myocardial dysfunction, cardiac arrhythmias, and congestive heart failure. In the Doberman Pinscher, the disease is typically adult onset, and a familial etiology has been suggested. Hypothesis: DCM in the Doberman Pinscher, is a familial disease linked to a specific genetic marker. Animals: The study comprised an extended family of Doberman Pinschers with a history of DCM. Methods: Participating dogs were prospectively evaluated over an 8‐year period. Phenotype of participating dogs was determined by annual echocardiography and ambulatory electrocardiography, and the pedigree was evaluated to determine a specific mode of inheritance. Three hundred seventy‐two microsatellite markers were selected and genotyped to cover the 38 autosomal chromosomes. Phenotyping, genotyping, and pedigree information was entered into a database, and parametric, 2‐point analysis was performed. Markers were considered to be linked to the development of DCM if the logarithm of odds LOD score was ±3.0. Results: An autosomal dominant mode of inheritance was defined by the appearance of the disease in multiple generations, equal gender representation (P = .973) and male‐to‐male transmission. A maximum LOD score of 1.31 was obtained for 1 marker on chromosome 20, a score not high enough to be associated with DCM. Conclusion: DCM in the Doberman Pinscher is a familial disease inherited as an autosomal dominant trait. The causative gene(s) responsible for this condition remain unresolved. Association studies by means of array technology may provide new insights into gene identification.}, number={5}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Meurs, Kathryn M. and Fox, Philip R. and Norgard, Michelle and Spier, Alan W. and Lamb, Allison and Koplitz, Shianne L. and Baumwart, Ryan D.}, year={2007}, month={Sep}, pages={1016–1020} } @article{meurs_norgard_ederer_hendrix_kittleson_2007, title={A substitution mutation in the myosin binding protein C gene in ragdoll hypertrophic cardiomyopathy}, volume={90}, ISSN={0888-7543}, url={http://dx.doi.org/10.1016/j.ygeno.2007.04.007}, DOI={10.1016/j.ygeno.2007.04.007}, abstractNote={Familial hypertrophic cardiomyopathy (HCM) is a primary myocardial disease with a prevalence of 1 in 500 in human beings. Causative mutations have been identified in several sarcomeric genes, including the cardiac myosin binding protein C (MYBPC3) gene. Heritable HCM also exists in a large-animal model, the cat, and we have previously reported a mutation in the MYBPC3 gene in the Maine coon breed. We now report a separate mutation in the MYBPC3 gene in ragdoll cats with HCM. The mutation changes a conserved arginine to tryptophan and appears to alter the protein structure. The ragdoll is not related to the Maine coon and the mutation identified is in a domain different from that of the previously identified feline mutation. The identification of two separate mutations within this gene in unrelated breeds suggests that these mutations occurred independently rather than being passed on from a common founder.}, number={2}, journal={Genomics}, publisher={Elsevier BV}, author={Meurs, Kathryn M. and Norgard, Michelle M. and Ederer, Martina M. and Hendrix, Kristina P. and Kittleson, Mark D.}, year={2007}, month={Aug}, pages={261–264} } @inbook{meurs_2007, place={Ames}, title={Boxer Cardiomyopathy}, booktitle={Five Minute Veterinary Consult}, publisher={Blackwell Publishing}, author={Meurs, K.M.}, year={2007}, pages={206–208} } @article{meurs_ederer_stern_2007, title={Desmosomal gene evaluation in Boxers with arrhythmogenic right ventricular cardiomyopathy}, volume={68}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.68.12.1338}, DOI={10.2460/ajvr.68.12.1338}, abstractNote={Abstract Objective—To sequence the exonic and splice site regions of the 4 desmosomal genes associated with the human form of familial arrhythmogenic right ventricular cardiomyopathy (ARVC) in Boxers with ARVC and identify a causative mutation. Animals—10 unrelated Boxers with ARVC and 2 unaffected Labrador Retrievers (control dogs). Procedures—Exonic and splice site regions of the 4 genes encoding the desmosomal proteins plakophilin-2, plakoglobin, desmoplakin, and desmoglein-2 were sequenced. Sequences were compared for nucleotide sequence changes between affected dogs and the published sequences for clinically normal dogs and between affected dogs and the control dogs. Base-pair changes were considered to be causative for ARVC if they were detected in an affected dog but not in unaffected dogs, and if they involved a conserved amino acid and changed that amino acid to one of a different polarity, acid-base status, or structure. Results—A causative mutation for ARVC in Boxers was not identified, although single nucleotide polymorphisms were detected in some affected dogs within exon 3 of the plakophilin-2 gene; exon 3 of the plakoglobin gene; exons 3 and 7 of the desmoglein-2 gene; and exons 6, 14, 15, and 24 of the desmoplakin gene. None of these changed the amino acid of the respective protein. Conclusions and Clinical Relevance—Mutations within the desmosomal genes associated with the development of ARVC in humans do not appear to be causative for ARVC in Boxers. Genomewide scanning for genetic loci of interest in dogs should be pursued.}, number={12}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Meurs, Kathryn M. and Ederer, Martina M. and Stern, Joshua A.}, year={2007}, month={Dec}, pages={1338–1341} } @article{koffas_fuentes_boswood_connolly_brockman_bonagura_meurs_koplitz_baumwart_2007, title={Double Chambered Right Ventricle in 9 Cats}, volume={21}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.2007.tb02931.x}, DOI={10.1111/j.1939-1676.2007.tb02931.x}, 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 ± 50 mm Hg. Concurrent abnormalities included a ventricular septal defect (n = 2); aortic malalignment, aortic insufficiency (n = 1); and congenital peritoneal‐pericardial diaphragmatic hernia (n = 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}, publisher={Wiley}, author={Koffas, H. and Fuentes, V. Luis 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}, month={Jan}, pages={76–80} } @article{baumwart_orvalho_meurs_2007, title={Evaluation of serum cardiac troponin I concentration in Boxers with arrhythmogenic right ventricular cardiomyopathy}, volume={68}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.68.5.524}, DOI={10.2460/ajvr.68.5.524}, abstractNote={Abstract Objective—To evaluate serum cardiac troponin I (cTnI) concentrations in Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC), unaffected (control) Boxers, and control non-Boxers. Animals—10 Boxers with a clinical diagnosis of ARVC defined by ≥ 1,000 ventricular premature complexes (VPCs)/24 h on an ambulatory ECG, 10 control Boxers assessed as normal by the presence of < 5 VPCs/24h, and 10 control non-Boxers. Procedures—Serum was extracted from a blood sample from each dog. Analysis of serum cTnI concentrations was performed. Results—Mean ± SD serum cTnI concentration was 0.142 ± 0.05 ng/mL for Boxers with ARVC, 0.079 ± 0.03 ng/mL for control Boxers, and 0.023 ± 0.01 ng/mL for control non-Boxers. A significant difference in serum cTnI concentrations was observed among the 3 groups. In the combined Boxer population (ie, Boxers with ARVC and control Boxers), a significant correlation was found between serum cTnI concentration and number of VPCs/24 h (r = 0.78) and between serum cTnI concentration and grade of ventricular arrhythmia (r = 0.77). Conclusions and Clinical Relevance—Compared with clinically normal dogs, Boxers with ARVC had a significant increase in serum cTnI concentration. For Boxers, correlations were found between serum cTnI concentration and number of VPCs/24 h and between concentration and the grade of arrhythmia. Because of the overlap in serum cTnI concentrations in control Boxers and Boxers with ARVC, future studies should evaluate the correlation of serum cTnI concentration with severity of disease in terms of degree of myocardial fibrofatty changes.}, number={5}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Baumwart, Ryan D. and Orvalho, João and Meurs, Kathryn M.}, year={2007}, month={May}, pages={524–528} } @inbook{meurs_2007, place={Ames}, title={Lamb A Ambulatory electrocardiography}, booktitle={Five-Minute Veterinary Consult}, publisher={Diagnostic Procedures and Laboratory Tests Blackwell Publishing}, author={Meurs, K.M.}, year={2007}, pages={312–314} } @article{atkins_keene_brown_coats_crawford_defrancesco_edwards_fox_lehmkuhl_luethy_et al._2007, title={Results of the veterinary enalapril trial to prove reduction in onset of heart failure in dogs chronically treated with enalapril alone for compensated, naturally occurring mitral valve insufficiency}, volume={231}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.231.7.1061}, DOI={10.2460/javma.231.7.1061}, abstractNote={Abstract Objective—To determine the efficacy of long-term enalapril administration in delaying the onset of congestive heart failure (CHF). Design—Placebo-controlled, double-blind, multicenter, randomized trial. Animals—124 dogs with compensated mitral valve regurgitation (MR). Procedures—Dogs randomly assigned to receive enalapril or placebo were monitored for the primary endpoint of onset of CHF for ≤ 58 months. Secondary endpoints included time from study entry to the combined endpoint of CHF-all-cause death; number of dogs free of CHF at 500, 1,000, and 1,500 days; and mean number of CHF-free days. Results—Kaplan-Meier estimates of the effect of enalapril on the primary endpoint did not reveal a significant treatment benefit. Chronic enalapril administration did have a significant benefit on the combined endpoint of CHF-all-cause death (benefit was 317 days [10.6 months]). Dogs receiving enalapril remained free of CHF for a significantly longer time than those receiving placebo and were significantly more likely to be free of CHF at day 500 and at study end. Conclusions and Clinical Relevance—Chronic enalapril treatment of dogs with naturally occurring, moderate to severe MR significantly delayed onset of CHF, compared with placebo, on the basis of number of CHF-free days, number of dogs free of CHF at days 500 and study end, and increased time to a combined secondary endpoint of CHF-all-cause death. Improvement in the primary endpoint, CHF-free survival, was not significant. Results suggest that enalapril modestly delays the onset of CHF in dogs with moderate to severe MR.}, number={7}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Atkins, Clarke E. and Keene, Bruce W. and Brown, William A. and Coats, Julie R. and Crawford, Mary Ann and DeFrancesco, Teresa C. and Edwards, N. Joel and Fox, Phillip R. and Lehmkuhl, Linda B. and Luethy, Michael W. and et al.}, year={2007}, month={Oct}, pages={1061–1069} } @article{macdonald_kittleson_kass_meurs_2007, title={Tissue Doppler Imaging in Maine Coon Cats with a Mutation of Myosin Binding Protein C with or without Hypertrophy}, volume={21}, DOI={10.1111/j.1939-1676.2007.tb02954.x}, abstractNote={Background: The cardiac myosin binding protein C gene is mutated in Maine Coon (MC) cats with familial hypertrophic cardiomyopathy.Hypotheses: Early diastolic mitral annular velocity is incrementally reduced from normal cats to MC cats with only an abnormal genotype to MC cats with abnormal genotype and hypertrophy.Animals:Group 1 consisted of 6 normal domestic shorthair cats, group 2 of 6 MC cats with abnormal genotype but no hypertrophy, and group 3 of 15 MC cats with hypertrophy and abnormal genotype.Methods:The genotype and echocardiographic phenotype of cats were determined, and the cats were divided into the 3 groups. Tissue Doppler imaging (TDI) of the lateral mitral annulus from the left apical 4‐chamber view was performed. Five nonconsecutive measurements of early diastolic mitral annular velocity (EM) or summated early and late diastolic velocity (EAsum) and heart rate were averaged.Results:There was an ordered reduction in Em‐EAsum as group number increased (group 1, range 9.7–14.7 cm/s; group 2, range 7.5–13.2 cm/s; group 3, range 4.5–14.1 cm/s;P= .001). Using the lower prediction limit for normal Em‐EAsum, the proportion of cats with normal Em‐EAsum decreased as the group number increased (P= .001). However, Em‐EAsum was reduced in only 3 of 6 cats in group 2.Conclusion: The incremental reduction of Em‐EAsum as group severity increased indicates that diastolic dysfunction is an early abnormality that occurs before hypertrophy development. TDI measurement of Em or EAsum of the lateral mitral annulus is an insensitive screening test for identification of phenotypically normal, genotypically affected cats.}, number={2}, journal={Journal of Veterinary Internal Medicine}, author={MacDonald, K.M. and Kittleson, M.D. and Kass, P.H. and Meurs, K.M.}, year={2007}, month={Mar}, pages={232–237} } @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={{"Label"=>"OBJECTIVES", "NlmCategory"=>"OBJECTIVE"} To characterize angiographic morphology and minimum internal transverse diameter of left-to-right shunting patent ductus arteriosus (PDA) in a large series of dogs. {"Label"=>"BACKGROUND", "NlmCategory"=>"BACKGROUND"} 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. {"Label"=>"ANIMALS, MATERIALS AND METHODS", "NlmCategory"=>"METHODS"} In 246 dogs representing 31 breeds with left-to-right shunting PDA, right lateral selective aortic angiograms were recorded and reviewed. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} 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 2.9mm (median, 2.5mm; range, 1.0-9.5mm) 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, 2.3mm [median, 2.2mm; range, 1.0-5.5mm]). {"Label"=>"CONCLUSIONS", "NlmCategory"=>"CONCLUSIONS"} 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{meurs_lacombe_dryburgh_fox_reiser_kittleson_2006, title={Differential expression of the cardiac ryanodine receptor in normal and arrhythmogenic right ventricular cardiomyopathy canine hearts}, volume={120}, ISSN={0340-6717 1432-1203}, url={http://dx.doi.org/10.1007/s00439-006-0193-2}, DOI={10.1007/s00439-006-0193-2}, abstractNote={Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a form of cardiomyopathy characterized by ventricular tachyarrhythmias and a fibrofatty infiltrate that is believed to preferentially affect the right ventricle. Mutations in the cardiac ryanodine receptor (RyR2) gene have been identified in some human families with a unique form of ARVC, ARVC2. Although the RyR2 has significant importance in excitation-contraction coupling across the ventricles, mutations in the gene encoding for it appear to have the greatest impact on the right ventricle in ARVC2. Using a canine model (boxer), the RyR2 protein and message RNA in the right ventricle, left ventricle and interventricular septum from normal dogs and dogs with ARVC were investigated by immunoblotting and real time PCR. The cardiac RyR2 message and protein expression were differentially expressed across the cardiac walls in the normal heart, with the lowest concentration expressed in the right ventricle (P < 0.05). The message and protein expression of the RyR2 were reduced in all chambers in the canine model of ARVC. We propose that the increased susceptibility of the right ventricle to ARVC may be associated with the lower baseline protein concentration of RyR2 in the normal right ventricle compared to the left ventricle and interventricular septum and that all three areas are equally affected in this canine model of ARVC. Using this naturally occurring model of canine ARVC, we may have provided new insights into the pathogenesis of this cardiomyopathy.}, number={1}, journal={Human Genetics}, publisher={Springer Science and Business Media LLC}, author={Meurs, Kathryn M. and Lacombe, Veronique A. and Dryburgh, Keith and Fox, Philip R. and Reiser, Peter R. and Kittleson, Mark D.}, year={2006}, month={May}, pages={111–118} } @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/m2) 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{parker_meurs_ostrander_2006, title={Finding cardiovascular disease genes in the dog}, volume={8}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2006.04.002}, DOI={10.1016/j.jvc.2006.04.002}, abstractNote={Recent advances in canine genomics are changing the landscape of veterinary biology, and by default, veterinary medicine. No longer are clinicians locked into traditional methods of diagnoses and therapy. Rather, major advances in canine genetics and genomics from the past five years are now changing the way the veterinarian of the 21st century practices medicine. First, the availability of a dense genome map gives canine genetics a much-needed foothold in comparative medicine, allowing advances made in human and mouse genetics to be applied to companion animals. Second, the recently released 7.5× whole genome sequence of the dog is facilitating the identification of hereditary disease genes. Finally, development of genetic tools for rapid screening of families and populations at risk for inherited disease means that the cost of identifying and testing for disease loci will significantly decrease in coming years. Out of these advances will come major changes in companion animal diagnostics and therapy. Clinicians will be able to offer their clients genetic testing and counseling for a myriad of disorders. In this review we summarize recent findings in canine genomics and discuss their application to the study of canine cardiac health.}, number={2}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Parker, Heidi G. and Meurs, Kathryn M. and Ostrander, Elaine A.}, year={2006}, month={Nov}, pages={115–127} } @article{meurs_sanchez_david_bowles_towbin_reiser_kittleson_munro_dryburgh_macdonald_et al._2005, title={A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy}, volume={14}, DOI={10.1093/hmg/ddi386}, abstractNote={Hypertrophic cardiomyopathy (HCM) is one of the most common causes of sudden cardiac death in young adults and is a familial disease in at least 60% of cases. Causative mutations have been identified in several sarcomeric genes, including the myosin binding protein C (MYBPC3) gene. Although numerous causative mutations have been identified, the pathogenetic process is still poorly understood. A large animal model of familial HCM in the cat has been identified and may be used for additional study. As the first spontaneous large animal model of this familial disease, feline familial HCM provides a valuable model for investigators to evaluate pathophysiologic processes and therapeutic (pharmacologic or genetic) manipulations. The MYBPC3 gene was chosen as a candidate gene in this model after identifying a reduction in the protein in myocardium from affected cats in comparison to control cats (P<0.001). DNA sequencing was performed and sequence alterations were evaluated for evidence that they changed the amino acid produced, that the amino acid was conserved and that the protein structure was altered. We identified a single base pair change (G to C) in the feline MYBPC3 gene in affected cats that computationally alters the protein conformation of this gene and results in sarcomeric disorganization. We have identified a causative mutation in the feline MYBPC3 gene that results in the development of familial HCM. This is the first report of a spontaneous mutation causing HCM in a non-human species. It should provide a valuable model for evaluating pathophysiologic processes and therapeutic manipulations.}, number={23}, journal={Human Molecular Genetics}, author={Meurs, K.M. and Sanchez, X. and David, R.M. and Bowles, N.E. and Towbin, J.A. and Reiser, P.J. and Kittleson, J.A. and Munro, M.J. and Dryburgh, K. and MacDonald, K.A. and et al.}, year={2005}, month={Dec}, pages={3587–3593} } @article{baumwart_meurs_2005, title={Assessment of plasma brain natriuretic peptide concentration in Boxers with arrhythmogenic right ventricular cardiomyopathy}, volume={66}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.2005.66.2086}, DOI={10.2460/ajvr.2005.66.2086}, abstractNote={Abstract Objective—To determine whether Boxers with a clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) have increased plasma concentrations of brain natriuretic peptide (BNP), compared with concentrations in clinically normal dogs. Animals—13 Boxers with ARVC, 9 clinically normal Boxers, 10 clinically normal non-Boxer dogs, and 5 hound dogs with systolic dysfunction. Procedure—All Boxers were evaluated via 24-hour ambulatory electrocardiography and echocardiography; the number of ventricular premature contractions (VPCs) per 24 hours was assessed. Hound dogs with cardiac pacing-induced systolic dysfunction (positive control dogs) and clinically normal non-Boxer dogs (negative control dogs) were evaluated echocardiographically. Three milliliters of blood was collected from each dog for measurement of plasma BNP concentration by use of a radioimmunoassay. Results—Mean ± SD plasma BNP concentration for the ARVC-affected Boxers, clinically normal Boxers, negative control dogs, and positive control dogs was 11.0 ± 4.6 pg/mL, 7.9 ± 3.2 pg/mL, 11.5 ± 4.9 pg/mL, and 100.8 ± 56.8 pg/mL, respectively. Compared with findings in the positive control group, plasma BNP concentration in each of the other 3 groups was significantly different. There was no significant difference in BNP concentration between the 2 groups of Boxers. A significant correlation between plasma BNP concentration and number of VPCs per 24 hours in the ARVC-affected Boxers was not identified. Conclusions and Clinical Relevance—A significant difference in BNP concentration between Boxers with ARVC and clinically normal Boxers was not identified. Results suggest that BNP concentration may not be an indicator of ARVC in Boxers. (Am J Vet Res 2005;66:2086–2089)}, number={12}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Baumwart, Ryan D. and Meurs, Kathryn M.}, year={2005}, month={Dec}, pages={2086–2089} } @inbook{meurs_2005, place={Philadelphia}, edition={6th}, title={Canine Myocardial Disease}, booktitle={Textbook of Veterinary Internal Medicine}, publisher={WB Saunders}, author={Meurs, K.M.}, year={2005}, pages={1077–1081} } @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={AbstractObjective—To identify clinical, echocardiographic, and electrocardiographic abnormalities in Boxers with cardiomyopathy and echocardiographic evidence of left ventricular systolic dysfunction.Design—Retrospective study.Animals—48 mature Boxers.Procedure—Medical records were reviewed for information on age; sex; physical examination findings; and results of electrocardiography, 24-hour ambulatory electrocardiography, thoracic radiography, and echocardiography.Results—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.Conclusions and Clinical Relevance—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. (J Am Vet Med Assoc2005;226:1102–1104)}, number={7}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Baumwart, R.B. and Meurs, K.M. and Atkins, C.E. and Bonagura, J.D. and DeFrancesco, T.C. and Keene, B.W. and Koplitz, S. and Fuentes, V. L. and Miller, M.W. and Rausch, W. and et al.}, year={2005}, pages={1102–1104} } @inbook{stabej_meurs_van oost_2005, title={Molecular genetics of dilated cardiomyaopthy in the dog}, booktitle={Canine Genetics}, publisher={Cold Spring Harbor}, author={Stabej, P. and Meurs, K.M. and van Oost, B.A.}, year={2005}, pages={365–382} } @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={AbstractObjective—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 Assoc2005;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{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{basso_fox_meurs_towbin_spier_calabrese_maron_thiene_2004, title={Arrhythmogenic Right Ventricular Cardiomyopathy Causing Sudden Cardiac Death in Boxer Dogs}, volume={109}, ISSN={0009-7322 1524-4539}, url={http://dx.doi.org/10.1161/01.cir.0000118494.07530.65}, DOI={10.1161/01.cir.0000118494.07530.65}, abstractNote={Background—Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary familial heart muscle disease associated with substantial cardiovascular morbidity and risk of sudden death. Efforts to discern relevant pathophysiological mechanisms have been impaired by lack of a suitable animal model.Methods and Results—ARVC was diagnosed in 23 boxer dogs (12 male; 9.1±2.3 years old). Clinical events alone or in combination included sudden death (n=9; 39%), ventricular arrhythmias of suspected right ventricular (RV) origin (n=19; 83%), syncope (n=12, 52%), and heart failure (n=3; 13%). Right ventricular enlargement or aneurysms occurred in 10 (43%). Striking histopathological abnormalities were present in each boxer dog but not in controls, including severe RV myocyte loss with replacement by fatty (n=15, 65%) or fibrofatty (n=8, 35%) tissue. Focal fibrofatty lesions were also present in both atria (n=8) and the left ventricle (LV) (n=11). Fatty replacement occupied substantially greater RV wall area in ARVC dogs than controls (40.4±18.8% versus 13.8±3.4%, respectively) (P<0.001); residual myocardium was correspondingly reduced (56.6±19.2% versus 84.8±3.8% in controls) (P<0.001). MRI demonstrated bright anterolateral and/or infundibular RV myocardial signals, confirmed as fat by histopathology. Myocarditis appeared in the RV (n=14, 61%) and LV (n=16, 70%) and in each dog with sudden death, but not in controls. Familial transmission was evident in 10 of the 23.Conclusions—We describe a novel, spontaneous, and genetically transmitted animal model of ARVC associated with sudden death in the boxer dog, closely resembling the human disease. This model may aid in understanding the pathogenic mechanisms of ARVC.}, number={9}, journal={Circulation}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Basso, Cristina and Fox, Philip R. and Meurs, Kathryn M. and Towbin, Jeffrey A. and Spier, Alan W. and Calabrese, Fiorella and Maron, Barry J. and Thiene, Gaetano}, year={2004}, month={Mar}, pages={1180–1185} } @article{spier_meurs_2004, title={Assessment of heart rate variability in Boxers with arrhythmogenic right ventricular cardiomyopathy}, volume={224}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2004.224.534}, DOI={10.2460/javma.2004.224.534}, abstractNote={AbstractObjective—To assess heart rate variability (HRV) in Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC), assess the ability of HRV analysis to identify differences in Boxers on the basis of severity of their arrhythmia, and evaluate the use of HRV to determine whether persistently high sympathetic tone is present in these dogs.Design—Prospective study.Animals—24 Boxers with ARVC and 10 clinically normal non-Boxer dogs.Procedure—Boxers were categorized as dogs with congestive heart failure (CHF), dogs with ≤ 2 ventricular premature complexes (VPCs)/24 h (designated unaffected), or dogs with > 1,000 VPCs/24 h (designated affected). Ambulatory electrocardiography (24 hours) was performed in each dog. Recordings were analyzed for HRV variables at a commercial laboratory; differences in HRV variables among groups were compared with 1-way ANOVA.Results—Compared with control non-Boxer dogs and Boxers without CHF (affected and unaffected Boxers), HRV was reduced in Boxers with CHF. No differences in HRV variables were detected between affected and unaffected Boxers. Inconsistent differences were identified between the control dogs and Boxers without CHF that had various degrees of arrhythmias.Conclusions and Clinical Relevance—Results suggest that persistently high sympathetic tone is not a consistent feature of ARVC. Differences in some HRV variables between Boxers without CHF and control dogs suggest that Boxers may have different autonomic control of heart rate, compared with that of clinically normal non-Boxer dogs. The usefulness of HRV analysis appears limited to Boxers with ARVC that have systolic dysfunction and CHF. (J Am Vet Med Assoc2004;224:534–537)}, number={4}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Spier, Alan W. and Meurs, Kathryn M.}, year={2004}, month={Feb}, pages={534–537} } @article{meurs_2004, title={Boxer dog cardiomyopathy: an update}, volume={34}, ISSN={0195-5616}, url={http://dx.doi.org/10.1016/j.cvsm.2004.05.003}, DOI={10.1016/j.cvsm.2004.05.003}, abstractNote={Boxer dog cardiomyopathy is an inheritable form of myocardial disease characterized most commonly by ventricular tachycardias, syncope, and, sometimes, systolic dysfunction and heart failure. Careful evaluation of boxer dog cardiomyopathy by several investigators has demonstrated that the disease may be best classified as arrhythmogenic right ventricular cardiomyopathy. Affected dogs have a variable prognosis; although some succumb to sudden cardiac death, many can remain asymptomatic or be successfully managed on antiarrhythmics for years.}, number={5}, journal={Veterinary Clinics of North America: Small Animal Practice}, publisher={Elsevier BV}, author={Meurs, Kathryn M.}, year={2004}, month={Sep}, pages={1235–1244} } @article{kraus_calvert_spier_meurs_anderson_2004, title={Determination of electrocardiographic parameters in healthy llamas and alpacas}, volume={65}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.2004.65.1719}, DOI={10.2460/ajvr.2004.65.1719}, abstractNote={Abstract Objective—To determine electrocardiographic parameters in healthy llamas and alpacas. Animals—23 llamas and 12 alpacas. Procedure—Electrocardiography was performed in nonsedated standing llamas and alpacas by use of multiple simultaneous lead recording (bipolar limb, unipolar augmented limb, and unipolar precordial leads). Results—Common features of ECGs of llamas and alpacas included low voltage of QRS complexes, variable morphology of QRS complexes among camelids, and mean depolarization vectors (mean electrical axes) that were directed dorsocranially and to the right. Durations of the QT interval and ST segment were negatively correlated with heart rate. Conclusions and Clinical Relevance—ECGs of acceptable quality can be consistently recorded in nonsedated standing llamas and alpacas. Features of ECGs in llamas and alpacas are similar to those of other ruminants. Changes in the morphology of the QRS complexes and mean electrical axis are unlikely to be sensitive indicators of ventricular enlargement in llamas and alpacas. (Am J Vet Res 2004;65:1719–1723)}, number={12}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Kraus, Marc S. and Calvert, Clay A. and Spier, Alan W. and Meurs, Kathryn M. and Anderson, David E.}, year={2004}, month={Dec}, pages={1719–1723} } @article{spier_meurs_2004, title={Evaluation of spontaneous variability in the frequency of ventricular arrhythmias in Boxers with arrhythmogenic right ventricular cardiomyopathy}, volume={224}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2004.224.538}, DOI={10.2460/javma.2004.224.538}, abstractNote={AbstractObjective—To evaluate spontaneous variability in the frequency of ventricular arrhythmias and assess the influence of day of ECG recording and day of week on arrhythmia frequency in Boxers affected with arrhythmogenic right ventricular cardiomyopathy (ARVC).Design—Prospective study.Animals—10 Boxers with ARVC with prior ambulatory ECG recordings that included ≥ 500 ventricular premature complexes/24 h.Procedure—Consecutive 24-hour ambulatory ECG recordings were obtained during a 7-day period in each dog. The number of ventricular premature complexes and grade of the arrhythmia were obtained from each recording. For each dog, the number of ventricular premature complexes for each recording was evaluated to identify any differences relative to the day of recording (recording 1 to 7) and day of the week (Monday through Sunday).Results—Spontaneous variability accounted for as much as 80% of the change in frequency of ventricular premature complexes in dogs with frequent arrhythmias; this value was almost 100% in dogs with less frequent arrhythmias. Grade of arrhythmia was less variable but was also inversely related to frequency of arrhythmia. No significant differences in frequency values were identified among days of recording or among days of the week.Conclusions and Clinical Relevance—Changes of ≤ 80% in the frequency of ventricular arrhythmias may be within the limit of spontaneous variability in dogs with ARVC. This degree of variability should be considered in evaluations of ambulatory ECG recordings, particularly in the assessment of the efficacy of antiarrhythmic drugs. (J Am Vet Med Assoc2004;224: 538–541)}, number={4}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Spier, Alan W. and Meurs, Kathryn M.}, year={2004}, month={Feb}, pages={538–541} } @article{davainis_meurs_wright_2004, title={The Relationship of Resting S-T Segment Depression to the Severity of Subvalvular Aortic Stenosis and the Presence of Ventricular Premature Complexes in the Dog}, volume={40}, ISSN={0587-2871 1547-3317}, url={http://dx.doi.org/10.5326/0400020}, DOI={10.5326/0400020}, abstractNote={Electrocardiograms (ECG) from 35 dogs with subvalvular aortic stenosis (SAS) with a left ventricular outflow tract pressure gradient (PG) of ≥50 mm Hg were retrospectively evaluated for S-T segment depression (STD, ≥0.2 mV in lead II). Pressure gradient, age, heart rate (HR), and number of ventricular premature complexes (VPCs) on a 24-hour ambulatory ECG for dogs with STD were not significantly different from those for dogs without STD. The S-T segment deviation did not correlate significantly with PG, age, HR, or VPCs. The significance of STD in the dog with SAS remains uncertain. Long-term prospective studies are needed to fully understand this observation.}, number={1}, journal={Journal of the American Animal Hospital Association}, publisher={American Animal Hospital Association}, author={Davainis, Grace M. and Meurs, Kathryn M. and Wright, Nicola A.}, year={2004}, month={Jan}, pages={20–23} } @article{spier_meurs_2004, title={Use of signal-averaged electrocardiography in the evaluation of arrhythmogenic right ventricular cardiomyopathy in Boxers}, volume={225}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2004.225.1050}, DOI={10.2460/javma.2004.225.1050}, abstractNote={AbstractObjective—To assess signal-averaged electrocardiography (SAECG) for evaluation of Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC) and identify dogs at risk for sudden death (SD) or death related to congestive heart failure (CHF).Design—Prospective study.Animals—94 Boxers with ARVC and 49 clinically normal non-Boxers (controls).Procedure—Boxers were screened for ARVC, and severity was estimated by use of echocardiography, 24-hour ambulatory ECG, and SAECG. Statistical evaluation was performed to identify significant differences in SAECG variables relative to clinical outcome, frequency of ventricular arrhythmias, and systolic function. Sensitivity, specificity, and positive and negative predictive values were evaluated for each SAECG variable for occurrence of SD or death related to CHF. Late potentials were also evaluated as a predictor of cardiac-related death.Results—Differences were detected in SAECG variables on the basis of clinical outcome, systolic function, and frequency of ventricular arrhythmias. More severely affected dogs had significantly more abnormal SAECG findings. The presence of late potentials, defined as 2 abnormal root mean square values (of 4), was associated with high sensitivity, specificity, and negative predictive value for cardiac-related SD or death secondary to CHF.Conclusions and Clinical Relevance—Results suggest that SAECG is a useful noninvasive diagnostic test to evaluate dogs affected with ARVC and identify individuals at risk for cardiac-related death. (J Am Vet Med Assoc2004;225:1050–1055)}, number={7}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Spier, Alan W. and Meurs, Kathryn M.}, year={2004}, month={Oct}, pages={1050–1055} } @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={AbstractObjective—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 Assoc2003;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}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.2003.tb02484.x}, DOI={10.1111/j.1939-1676.2003.tb02484.x}, 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: nout.1@osu.eduSearch 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: nout.1@osu.eduSearch 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 Share a linkShare onFacebookTwitterLinkedInRedditWechat 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. Myocarditis following envenoming with Vipera palaestinae in two horses. Toxicon 1993; 31: 1623– 1628. 4 Peet RL, McDermott J., Williams JM, Maclean AA. Fungal myocarditis and nephritis in a horse. Aust Vet J 1981; 57: 439– 440. 5 Cranley JJ, McCullagh KG. Ischaemic myocardial fibrosis and aortic strongylosis in the horse. Equine Vet J 1981; 13: 35– 42. 6 Bonagura JD, Reef VB. Cardiovascular diseases. In: SM Reed, WM Bayly, eds. Equine Internal Medicine. Philadelphia , PA : WB Saunders; 1998; 290– 370. 7 Reef VB. Equine diagnostic ultrasound. Philadelphia , PA : WB Saunders; 1998: 222, 249– 254. 8 Keren A., Popp RL. Assignment of patients into the classification of cardiomyopathies. Circulation 1992; 86: 1622– 1633. 9 Ammash NM, Seward JB, Bailey KR, et al. Clinical profile and outcome of idiopathic restrictive cardiomyopathy. Circulation 2000; 101: 2490– 2496. 10 Artz G., Wynne J. Restrictive cardiomyopathy. Curr Treat Options Cardiovasc Med 2000; 2: 431– 438. 11 Felker GM, Thompson RE, Hare JM, et al. Underlying causes and long-term survival in patients with initially unexplained cardio-myopathy. N Engl J Med 2000; 342: 1077– 1084. 12 Brummer DG, Moise NS. Infiltrative cardiomyopathy responsive to combination chemotherapy in a cat with lymphoma. J Am Vet Med Assoc 1989; 195: 1116– 1119. 13 Stalis IH, Bossbaly MJ, Van Winkle TJ. Feline endomyocarditis and left ventricular endocardial fibrosis. Vet Pathol 1995; 32: 122– 126. 14 Fox PR. Feline cardiomyopathies. In: PR Fox, DD Sisson, NS Mo-ise, eds. Textbook of canine and feline cardiology, 2nd ed. Philadelphia , PA : WB Saunders; 1999: 641– 645. 15 La Vecchia L., Mezzena G., Zanolla L., et al. 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Amyloid in the horse: A report of nine cases. Equine Vet J 1988; 20: 277– 285. 24 Mould JR, Munroe GA, Eckersall PD, et al. Conjunctival and nasal amyloidosis in a horse. 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}, publisher={Wiley}, author={Nout, Yvette S. and Hinchcliff, Kenneth W. and Bonagura, John D. and Meurs, Kathryn M. and Papenfuss, Tracey L.}, year={2003}, month={Jul}, pages={588–592} } @inbook{meurs_2003, place={Philadelphia}, edition={4th}, title={Myocardial Disease}, booktitle={Handbook of Small Animal Practice}, publisher={WB Saunders}, author={Meurs, K.M.}, editor={Morgan, Rhea V. and Bright, Ronald and Swartout, MargaretEditors}, year={2003}, pages={101–111} } @article{meurs_spier_wright_atkins_defrancesco_gordon_hamlin_keene_miller_moise_et al._2002, title={Comparison of the effects of four antiarrhythmic treatments for familial ventricular arrhythmias in Boxers}, volume={221}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2002.221.522}, DOI={10.2460/javma.2002.221.522}, abstractNote={Abstract Objective—To evaluate the effect of 4 antiarrhythmic treatment protocols on number of ventricular premature complexes (VPC), severity of arrhythmia, heart rate (HR), and number of syncopal episodes in Boxers with ventricular tachyarrhythmias. Design—Randomized controlled clinical trial. Animals—49 Boxers. Procedure—Dogs with > 500 VPC/24 h via 24-hour ambulatory ECG (AECG) were treated with atenolol (n = 11), procainamide (11), sotalol (16), or mexiletine and atenolol (11) for 21 to 28 days. Results of pre- and posttreatment AECG were compared with regard to number of VPC/24 h; maximum, mean, and minimum HR; severity of arrhythmia; and occurrence of syncope. Results—Significant differences between pre- and posttreatment number of VPC, severity of arrhythmia, HR variables, or occurrence of syncope were not observed in dogs treated with atenolol or procainamide. Significant reductions in number of VPC, severity of arrythmia, and maximum and mean HR were observed in dogs treated with mexiletineatenolol or sotalol; occurrence of syncope was not significantly different between these 2 treatment groups. Conclusions and Clinical Relevance—Treatment with sotalol or mexiletine-atenolol was well tolerated and efficacious. Treatment with procainamide or atenolol was not effective. (J Am Vet Med Assoc 2002;221:522–527)}, number={4}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Meurs, K. M. and Spier, A. W. and Wright, N. A. and Atkins, C. E. and DeFrancesco, Teresa and Gordon, S. G. and Hamlin, R. L. and Keene, B. W. and Miller, M. W. and Moise, N. S. and et al.}, year={2002}, month={Aug}, pages={522–527} } @article{atkins_brown_coats_crawford_defrancesco_edwards_fox_keene_lehmkuhl_luethy_et al._2002, title={Effects of long-term administration of enalapril on clinical indicators of renal function in dogs with compensated mitral regurgitation}, volume={221}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2002.221.654}, DOI={10.2460/javma.2002.221.654}, abstractNote={AbstractObjective—To determine the effect of long-term administration of enalapril on renal function in dogs with severe, compensated mitral regurgitation.Design—Randomized controlled trial.Animals—139 dogs with mitral regurgitation but without overt signs of heart failure.Procedure—Dogs were randomly assigned to be treated with enalapril (0.5 mg/kg [0.23 mg/lb], PO, q 24 h) or placebo, and serum creatinine and urea nitrogen concentrations were measured at regular intervals for up to 26 months.Results—Adequate information on renal function was obtained from 132 dogs; follow-up time ranged from 0.5 to 26 months (median, 12 months). Mean serum creatinine and urea nitrogen concentrations were not significantly different between dogs receiving enalapril and dogs receiving the placebo at any time, nor were concentrations significantly different from baseline concentrations. Proportions of dogs that developed azotemia or that had a ≥ 35% increase in serum creatinine or urea nitrogen concentration were also not significantly different between groups.Conclusions and Clinical Relevance—Results suggest that administration of enalapril for up to 2 years did not have any demonstrable adverse effects on renal function in dogs with severe, compensated mitral regurgitation. (J Am Vet Med Assoc2002;221: 654–658)}, number={5}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Atkins, Clarke E. and Brown, William A. and Coats, Julie R. and Crawford, Mary Ann and DeFrancesco, Teresa C. and Edwards, Joel and Fox, Philip R. and Keene, Bruce W. and Lehmkuhl, Linda and Luethy, Michael and et al.}, year={2002}, month={Sep}, pages={654–658} } @article{meurs_fox_miller_kapadia_mann_2002, title={Plasma concentrations of tumor necrosis factor-α in cats with congestive heart failure}, volume={63}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.2002.63.640}, DOI={10.2460/ajvr.2002.63.640}, abstractNote={Abstract Objective—To determine whether plasma concentrations of tumor necrosis factor-α (TNF-α) are increased in cats with congestive heart failure (CHF) secondary to cardiomyopathy. Animals—26 adult cats with CHF and cardiomyopathy and 9 healthy control cats. Procedure—Plasma concentrations of TNF-α were measured in cats with CHF and cardiomyopathy. Tumor necrosis factor-α was measured by quantifying cytotoxic effects of TNF-α on L929 murine fibrosarcoma cells. Results—Concentrations of TNF-α were increased (0.13 to 3.6 U/ml) in 10 of 26 cats with CHF but were undetectable in the other 16 cats with CHF and all control cats. In 20 of 26 cats with CHF, right-sided heart failure (RHF) was evident; TNF-α concentrations were increased in 9 of these 20 cats. The remaining 6 cats had left-sided heart failure (LHF); TNF-α concentrations were increased in only 1 of these cats. Age of cats with LHF (mean ± SD, 12.1 ± 6.2 years) was not significantly different from age of the cohort with RHF (10.5 ± 5.2 years). Body weight of cats with increased TNFα concentrations (5.4 ± 1.8 kg) was not significantly different from body weight of cats with CHF that did not have measurable concentrations of TNF-α (4.7 ± 1.6 kg). Conclusionss and Clinical Relevance—Concentrations of TNF-α were increased in many cats with CHF. Cats with RHF were most likely to have increased TNF-α concentrations. Increased plasma concentrations of TNF-α in cats with CHF may offer insights into the pathophysiologic mechanisms of heart failure and provide targets for therapeutic interventions. (Am J Vet Res 2002;63:640–642)}, number={5}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Meurs, Kathryn M. and Fox, Philip R. and Miller, Matthew W. and Kapadia, Samir and Mann, Douglas L.}, year={2002}, month={May}, pages={640–642} } @article{meurs_miller_wright_2001, title={Clinical features of dilated cardiomyopathy in Great Danes and results of a pedigree analysis: 17 cases (1990-2000)}, volume={218}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2001.218.729}, DOI={10.2460/javma.2001.218.729}, abstractNote={AbstractObjective—To determine clinical features of dilated cardiomyopathy (DCM) in Great Danes and to determine whether DCM is familial in this breed.Design—Retrospective study.Animals—17 Great Danes with DCM.Procedure—Medical records of Great Danes in which DCM was diagnosed on the basis of results of echocardiography (fractional shortening < 25%, endsystolic volume index > 30 ml/m2of body surface area) were reviewed. Pedigrees were obtained for affected animals, as well as for other Great Danes in which DCM had been diagnosed.Results—Dilated cardiomyopathy appeared to be familial and was characterized by ventricular dilatation, congestive heart failure (left-sided or biventricular), and atrial fibrillation. Pedigree analysis suggested that DCM was inherited as an X-linked recessive trait, but the mode of inheritance could not be definitively identified.Conclusions and Clinical Relevance—Results suggest that DCM may be an X-linked recessive trait in Great Danes. Thus, dogs with DCM probably should not be used for breeding, and female offspring of affected dogs should be used cautiously. Male offspring of affected females are at an increased risk of developing DCM and should be evaluated periodically for early signs of disease. Results of pedigree analysis were preliminary and should be used only as a guide for counseling breeders, rather than as a basis for making breeding decisions. (J Am Vet Med Assoc2001;218:729–732)}, number={5}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Meurs, Kathryn M. and Miller, Matthew W. and Wright, Nicola A.}, year={2001}, month={Mar}, pages={729–732} } @article{meurs_spier_wright_hamlin_2001, title={Comparison of in-hospital versus 24-hour ambulatory electrocardiography for detection of ventricular premature complexes in mature Boxers}, volume={218}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2001.218.222}, DOI={10.2460/javma.2001.218.222}, abstractNote={AbstractObjective—To evaluate the use of in-hospital electrocardiography (ECG) for detection of ventricular premature complexes (VPC), compared with 24-hour ambulatory ECG.Design—Original study.Animals—188 Boxers > 9 months old; 31 had a history of syncope, and 157 were healthy (no history of syncope).Procedure—In-hospital ECG was performed on all Boxers for at least 2 minutes. Within 7 days after the in-hospital ECG was completed, 24-hour ambulatory ECG was performed.Results—The specificity of in-hospital ECG was 100% for the detection of at least 50 VPC in a 24-hour period in dogs with syncope and 93% in healthy dogs. In-hospital ECG had poor sensitivity, although sensitivity increased as the number of VPC per 24 hours increased.Conclusions and Clinical Relevance—Use of in-hospital ECG is highly specific for detection of at least 50 VPC during a 24-hour period. However, in-hospital ECG is insensitive, and a lack of VPC does not suggest that the dog does not have a substantial number of VPC during that same period. The use of in-hospital ECG appears to be inadequate for screening purposes and therapeutic evaluations in mature Boxers with ventricular arrhythmic disease. (J Am Vet Med Assoc2001;218:222–224)}, number={2}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Meurs, Kathryn M. and Spier, Alan W. and Wright, Nicola A. and Hamlin, Robert L.}, year={2001}, month={Jan}, pages={222–224} } @article{spier_meurs_muir_lehmkuhl_hamlin_2001, title={Correlation of QT dispersion with indices used to evaluate the severity of familial ventricular arrhythmias in Boxers}, volume={62}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.2001.62.1481}, DOI={10.2460/ajvr.2001.62.1481}, abstractNote={Abstract Objective—To measure QT interval duration and QT dispersion in Boxers and to determine whether QT variables correlate with indices of disease severity in Boxers with familial ventricular arrhythmias, including the number of ventricular premature complexes per day, arrhythmia grade, and fractional shortening. Animals—25 Boxers were evaluated by ECG and echocardiography. Procedure—The QT interval duration was measured from 12-lead ECG and corrected for heart rate (QTc), using Fridericia's formula. The QT and QTc were calculated for each lead, from which QT and QTc dispersion were determined. Echocardiography and 24-hour ambulatory ECG were performed to evaluate for familial ventricular arrhythmias. Total number of ventricular premature complexes, arrhythmia grade, and fractional shortening were determined and used as indices of disease severity. Results—There was no correlation between any QT variable and total number of ventricular premature complexes, arrhythmia grade, or fractional shortening. No difference between QT dispersion and QTc dispersion was identified, and correction for heart rate did not affect the results. Conclusions and Clinical Relevance—QT interval duration and dispersion did not correlate with indices of disease severity for familial ventricular arrhythmias. Heart rate correction of the QT interval did not appear to be necessary for QT dispersion calculation in this group of dogs. QT dispersion does not appear to be a useful noninvasive diagnostic tool in the evaluation of familial ventricular arrhythmias of Boxers. Identification of affected individuals at risk for sudden death remains a challenge in the management of this disease. (Am J Vet Res 2001;62:1481–1485)}, number={9}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Spier, Alan W. and Meurs, Kathryn M. and Muir, William W. and Lehmkuhl, Linda B. and Hamlin, Robert L.}, year={2001}, month={Sep}, pages={1481–1485} } @article{meurs_magnon_spier_miller_lehmkuhl_towbin_2001, title={Evaluation of the cardiac actin gene in Doberman Pinschers with dilated cardiomyopathy}, volume={62}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.2001.62.33}, DOI={10.2460/ajvr.2001.62.33}, abstractNote={Abstract Objective—To evaluate the coding region of the cardiac actin gene in Doberman Pinschers with dilated cardiomyopathy (DCM) for mutations that could be responsible for the development of the condition Animals—28 dogs (16 Doberman Pinschers with DCM and 12 mixed-breed control dogs). Procedure—Ten milliliters of blood was collected from each dog for DNA extraction. Polymerase chain reaction (PCR) primers were designed to amplify canine exonic regions, using the sequences of exons 2 to 6 of the cardiac actin gene. Single-stranded conformational polymorphism analysis was performed for each exon with all samples. Autoradiographs were analyzed for banding patterns specific to affected dogs. The DNA sequencing was performed on a selected group of affected and control dogs. Results—Molecular analysis of exons 2 to 6 of the cardiac actin gene did not reveal any differences in base pairs between affected dogs and control dogs selected for DNA evaluation. Conclusions—Mutations in exons 5 and 6 of the cardiac actin gene that have been reported in humans with familial DCM do not appear to be the cause of familial DCM in Doberman Pinschers. Additionally, evaluation of exons 2 to 6 for causative mutations did not reveal a cause for inherited DCM in these Doberman Pinschers. Although there is evidence that DCM in Doberman Pinschers is an inherited problem, a molecular basis for this condition remains unresolved. Evaluation of other genes coding for cytoskeletal proteins is warranted. ( Am J Vet Res 2001;62:33–36)}, number={1}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Meurs, Kathryn M. and Magnon, Alex L. and Spier, Alan W. and Miller, Mathew W. and Lehmkuhl, Linda B. and Towbin, Jeffrey A.}, year={2001}, month={Jan}, pages={33–36} } @inbook{meurs_spier_2001, title={Hypertrophic Cardiomyopathy}, volume={IV}, booktitle={Consultations in Feline Internal Medicine}, publisher={WB Saunders}, author={Meurs, K.M. and Spier, A.W.}, year={2001}, pages={56–78} } @article{maxson_meurs_lehmkuhl_magnon_weisbrode_atkins_2001, title={Polymerase chain reaction analysis for viruses in paraffin-embedded myocardium from dogs with dilated cardiomyopathy or myocarditis}, volume={62}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.2001.62.130}, DOI={10.2460/ajvr.2001.62.130}, abstractNote={AbstractObjective—To perform polymerase chain reaction (PCR) analysis on paraffin-embedded myocardium from dogs with dilated cardiomyopathy (DCM) and dogs with myocarditis to screen for canine parvovirus, adenovirus types 1 and 2, and herpesvirus.Sample Population—Myocardial specimens from 18 dogs with an antemortem diagnosis of DCM and 9 dogs with a histopathologic diagnosis of myocarditis were evaluated.Procedure—Paraffin-embedded myocardial specimens were screened for viral genome by PCR analysis. Positive-control specimens were developed from cell cultures as well as paraffin-embedded tissue specimens from dogs with clinical and histopathologic diagnoses of viral infection with canine parvovirus, adenovirus types 1 and 2, and herpesvirus. The histologic characteristics of all myocardial specimens were classified regarding extent, location, and type of inflammation and fibrosis.Results—Canine adenovirus type 1 was amplified from 1 specimen from a dog with DCM. Canine parvovirus, adenovirus type 2, and herpesvirus were not amplified from any myocardial specimens. Histologic analysis of specimens from dogs with DCM revealed variable amounts of fibrosis; myocardial inflammation was observed in 1 affected dog. Histopathologic analysis of specimens from dogs with myocarditis disclosed variable degrees of inflammation and fibrosis.Conclusions and Clinical Relevance—Viral agents canine parvovirus, adenovirus types 1 and 2, and herpesvirus are not commonly associated with DCM or active myocarditis in dogs. Additional studies evaluating for nucleic acid from viruses that less commonly affect dogs or different types of infectious agents may be warranted to gain insight into the cause of DCM and myocarditis in dogs. (Am J Vet Res2001;62: 130–135)}, number={1}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Maxson, Tracy R. and Meurs, Kathryn M. and Lehmkuhl, Linda B. and Magnon, Alex L. and Weisbrode, Steven E. and Atkins, Clarke E.}, year={2001}, month={Jan}, pages={130–135} } @article{meurs_spier_wright_hamlin_2001, title={Use of ambulatory electrocardiography for detection of ventricular premature complexes in healthy dogs}, volume={218}, DOI={10.2460/javma.2001.218.1291}, abstractNote={AbstractObjective—To evaluate the use of 24-hour ambulatory electrocardiography (AECG) for the detection of ventricular premature complexes (VPC) in healthy dogs.Design—Case series.Animals—50 healthy mature dogs.Procedure—A 24-hour AECG was performed on each dog and evaluated for the presence of VPC.Results—Fifty dogs weighing between 18.2 to 40.9 kg (40 and 90 lb) representing 13 breeds were evaluated; there were 4 sexually intact females, 21 spayed females, 4 sexually intact males, and 21 castrated males. Ages ranged from 1 to 12 years. Thirty-four dogs had no VPC; 16 dogs had between 1 and 24 VPC. The grade of arrhythmia ranged from 1 to 4, with 4 dogs having an arrhythmia with a grade > 1. Significant differences were not detected between the group of dogs with VPC and those without VPC with regard to sex, age, and minimum, maximum, or mean heart rate.Conclusions and Clinical Relevance—We conclude that healthy mature dogs have infrequent VPC, as detected by use of 24-hour AECG. The presence of numerous or sequential VPC may be suggestive of cardiac or systemic disease and may indicate the need for thorough clinical evaluation. (J Am Vet Med Assoc2001;218:1291–1292)}, number={8}, journal={Journal of the American Veterinary Medical Association}, author={Meurs, K.M. and Spier, A.W. and Wright, N.A. and Hamlin, R.A.}, year={2001}, month={Apr}, pages={1291–1295} } @article{defrancesco_atkins_miller_meurs_keene_2001, title={Use of echocardiography for the diagnosis of heartworm disease in cats: 43 cases (1985-1997)}, volume={218}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2001.218.66}, DOI={10.2460/javma.2001.218.66}, abstractNote={AbstractObjective—To determine the usefulness of echocardiography in the diagnosis of heartworm disease in cats and to compare this modality with other tests.Design—Retrospective study.Animals—43 cats with heartworm infection that had echocardiographic examinations at 2 veterinary teaching hospitals between 1985 and 1997. Twenty-two of these 43 cats also underwent radiography of the thorax and heartworm antibody and heartworm antigen testing.Procedure—Cats were determined to be infected withDirofilaria immitisinfection on the basis of 1 or more of the following findings: positive modified Knott or antigen test result, echocardiographic evidence of heartworm disease, or confirmation of the disease on postmortem examination. The percentage of echocardiographs in which heartworms were evident was compared with the percentage of radiographs in which pulmonary artery enlargement was evident and results of antigen or antibody tests in cats in which all tests were performed.Results—Overall, heartworms were detectable by use of echocardiography in 17 of 43 cats, most often in the pulmonary arteries. In the 22 cats in which all tests were performed, antibody test results were positive in 18, antigen test results were positive in 12, and pulmonary artery enlargement was evident radiographically and heartworms were identifiable echocardiographically in 14. Heartworm infection was diagnosed exclusively by use of echocardiography in 5 cats in which the antigen test result was negative.Conclusions and Clinical Relevance—Although echocardiography was less sensitive than antigen testing, it was a useful adjunctive test in cats that had negative antigen test results in which there was a suspicion of heartworm disease. The pulmonary arteries should be evaluated carefully to increase the likelihood of detection of heartworms echocardiographically. ( J Am Vet Med Assoc2001;218:66–69)}, number={1}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={DeFrancesco, Teresa C. and Atkins, Clarke E. and Miller, Matthew W. and Meurs, Kathryn M. and Keene, Bruce W.}, year={2001}, month={Jan}, pages={66–69} } @article{spier_meurs_coovert_lehmkuhl_o'grady_freeman_burghes_towbin_2001, title={Use of western immunoblot for evaluation of myocardial dystrophin, -sarcoglycan, and -dystroglycan in dogs with idiopathic dilated cardiomyopathy}, volume={62}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.2001.62.67}, DOI={10.2460/ajvr.2001.62.67}, abstractNote={AbstractObjective—To evaluate the potential importance of dystrophin, α-sarcoglycan (adhalin), and β-dystroglycan, by use of western blot analysis, in several breeds of dogs with dilated cardiomyopathy.Sample Population—Myocardial samples obtained from 12 dogs were evaluated, including tissues from 7 dogs affected with dilated cardiomyopathy, 4 control dogs with no identifiable heart disease (positive control), and 1 dog affected with Duchenne muscular dystrophy (negative control for dystrophin). Of the affected dogs, 4 breeds were represented (Doberman Pinscher, Dalmatian, Bullmastiff, and Irish Wolfhound).Procedure—Western blot analysis was used for evaluation of myocardial samples obtained from dogs with and without dilated cardiomyopathy for the presence of dystrophin and 2 of its associated glycoproteins, α-sarcoglycan and β-dystroglycan.Results—Detectable differences were not identified between dogs with and without myocardial disease in any of the proteins evaluated.Conclusions and Clinical Relevance—Abnormalities in dystrophin, α-sarcoglycan, and β-dystroglycan proteins were not associated with the development of dilated cardiomyopathy in the dogs evaluated in this study. In humans, the development of molecular biological techniques has allowed for the identification of specific causes of dilated cardiomyopathy that were once considered to be idiopathic. The use of similar techniques in veterinary medicine may aid in the identification of the cause of idiopathic dilated cardiomyopathy in dogs, and may offer new avenues for therapeutic intervention. (Am J Vet Res2001;62:67–71)}, number={1}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Spier, Alan W and Meurs, Kathryn M. and Coovert, Daniel D and Lehmkuhl, Linda B. and O'Grady, Michael R. and Freeman, Lisa M. and Burghes, Arthur H. and Towbin, Jeffrey A.}, year={2001}, month={Jan}, pages={67–71} } @article{magnon_meurs_kittleson_ware_2000, title={A highly polymorphic marker identified in intron 15 of the feline cardiac troponin T gene by SSCP analysis}, volume={31}, journal={Animal Genetics}, author={Magnon, A.L. and Meurs, K.M. and Kittleson, M.D. and Ware, W.A.}, year={2000}, pages={236–237} } @article{meurs_miller_slater_glaze_2000, title={Arterial blood pressure measurement in a population of healthy geriatric dogs}, volume={36}, ISSN={0587-2871 1547-3317}, url={http://dx.doi.org/10.5326/15473317-36-6-497}, DOI={10.5326/15473317-36-6-497}, abstractNote={The purpose of this study was to evaluate healthy geriatric dogs for the presence of systemic hypertension. Thirty-three geriatric dogs (i.e., dogs exceeding the geriatric age range for their weight group) and 22 control dogs (i.e., dogs less than six years of age) were evaluated by measuring blood pressure with an oscillometric monitor. Five consecutive blood pressure measurements were taken in each dog, averaged, and compared. Diastolic and mean blood pressure measurements were significantly lower in the geriatric group as compared to the control group. Systolic blood pressure measurements were not significantly different between the two groups. Systemic hypertension does not appear to be a common clinical problem in the healthy geriatric dog.}, number={6}, journal={Journal of the American Animal Hospital Association}, publisher={American Animal Hospital Association}, author={Meurs, KM and Miller, MW and Slater, MR and Glaze, K}, year={2000}, month={Nov}, pages={497–500} } @article{meurs_fox_magnon_liu_towbin_2000, title={Molecular Screening by Polymerase Chain Reaction Detects Panleukopenia Virus DNA in Formalin-Fixed Hearts from Cats with Idiopathic Cardiomyopathy and Myocarditis}, volume={9}, ISSN={1054-8807}, url={http://dx.doi.org/10.1016/s1054-8807(00)00031-4}, DOI={10.1016/s1054-8807(00)00031-4}, abstractNote={Viral myocarditis has been suggested as an etiology for cardiomyopathy in several mammalian species. Myocarditis and idiopathic cardiomyopathy have been reported in the domestic cat, although a viral etiology has not been demonstrated. Because of the continuing interest in the potential relationship between viral myocarditis and cardiomyopathy, we evaluated hearts from cats with spontaneous, idiopathic cardiomyopathy for viral genomic material within myocytes by polymerase chain reaction, and for the presence of myocarditis by light microscopy. Thirty-one (31) formalin-fixed hearts from domestic cats who died of idiopathic cardiomyopathy were randomly selected from pathology archives. Seventeen (17) formalin-fixed hearts from healthy cats were similarly selected as normal controls. The polymerase chain reaction (PCR) was used to evaluate myocardial tissue for the presence of viral genome from feline panleukopenia virus, herpes virus, calici virus, and corona virus. Hearts were examined using light microscopy for histologic evidence of myocarditis according to the Dallas criteria. Panleukopenia virus was identified by PCR in 10 of 31 cats with cardiomyopathy but in none of the controls. Neither cardiomyopathic or control cats tested positive by PCR for herpes virus, calici virus, and corona virus. Myocarditis was detected by histologic examination in 18 of 31 cardiomyopathic cats and in none of 17 control cats. Myocarditis and or feline panleukopenia virus genome was detected in felines with idiopathic hypertrophic, dilated, and restrictive cardiomyopathy, suggesting a possible role of viral infection and inflammation in the pathogenesis of cardiomyopathy in this species.}, number={2}, journal={Cardiovascular Pathology}, publisher={Elsevier BV}, author={Meurs, Kathryn M and Fox, Philip R and Magnon, Alexander L and Liu, Si-Kwang and Towbin, Jeffrey A}, year={2000}, month={Mar}, pages={119–126} } @article{magnon_meurs_kittleson_ware_2000, title={Single nucleotide polymorphisms in intron 5 of the feline myosin regulatory light chain gene detected by SSCP analysis}, volume={31}, ISSN={0268-9146 1365-2052}, url={http://dx.doi.org/10.1046/j.1365-2052.2000.00620.x}, DOI={10.1046/j.1365-2052.2000.00620.x}, abstractNote={Recently, we published the mapping of the chicken leptin gene to a microchromosome. This work was done through PCR-SSCP analysis, using primers designed from a published sequence (, EMBL accession number AF012727), presenting 97% similarity to the mouse and 83% to the human leptin genes. This sequence was also published by another group and the primers were therefore supposed to be homologous ones. We have now sequenced our PCR product: although it was amplified with primers chosen from a chicken sequence, it is neither homologous to the published leptin sequence, nor to any other sequence in Genebank/EMBL databases. Therefore, the amplimer we have localised can not be considered as a part of the chicken leptin gene.}, number={4}, journal={Animal Genetics}, publisher={Wiley}, author={Magnon, A L and Meurs, K M and Kittleson, M D and Ware, W A}, year={2000}, month={Aug}, pages={281–282} } @article{meurs_kittleson_ware_miller_2000, title={The identification of nine polymorphisms identified within the head region of feline Beta Myosin heavy chain gene}, volume={31}, journal={Animal Genetics}, author={Meurs, K.M. and Kittleson, M.D. and Ware, W.A. and Miller, M.W.}, year={2000}, pages={231} } @inbook{calvert_meurs_2000, place={Philadelphia}, title={Update on Doberman pinscher cardiomyopathy}, booktitle={Current Veterinary Therapy (Small Animal Practice) XIII}, publisher={WB Saunders}, author={Calvert, C. and Meurs, K.M.}, year={2000}, pages={756–760} } @article{schatzberg_olby_steingold_keene_atkins_meurs_solomon_goedegebuure_wilton_sharp_1999, title={A polymerase chain reaction screening strategy for the promoter of the canine dystrophin gene}, volume={60}, number={9}, journal={American Journal of Veterinary Research}, author={Schatzberg, S. and Olby, N. and Steingold, S. and Keene, B. and Atkins, C. and Meurs, K.M. and Solomon, G. and Goedegebuure, S.A. and Wilton, S. and Sharp, N.}, year={1999}, month={Aug}, pages={1040–1046} } @article{kittleson_meurs_munro_kittleson_liu_pion_towbin_1999, title={Familial Hypertrophic Cardiomyopathy in Maine Coon Cats}, volume={99}, DOI={10.1161/01.cir.99.24.3172}, abstractNote={ Background —A naturally occurring animal model of familial hypertrophic cardiomyopathy (FHCM) is lacking. We identified a family of Maine coon cats with HCM and developed a colony to determine mode of inheritance, phenotypic expression, and natural history of the disease. Methods and Results —A proband was identified, and related cats were bred to produce a colony. Affected and unaffected cats were bred to determine the mode of inheritance. Echocardiography was used to identify affected offspring and determine phenotypic expression. Echocardiograms were repeated serially to determine the natural history of the disease. Of 22 offspring from breeding affected to unaffected cats, 12 (55%) were affected. When affected cats were bred to affected cats, 4 (45%) of the 9 were affected, 2 (22%) unaffected, and 3 (33%) stillborn. Findings were consistent with an autosomal dominant mode of inheritance with 100% penetrance, with the stillborns representing lethal homozygotes that died in utero. Affected cats usually did not have phenotypic evidence of HCM before 6 months of age, developed HCM during adolescence, and developed severe HCM during young adulthood. Papillary muscle hypertrophy that produced midcavitary obstruction and systolic anterior motion of the mitral valve was the most consistent manifestation of HCM. Cats died suddenly (n=5) or of heart failure (n=3). Histopathology of the myocardium revealed myocardial fiber disarray, intramural coronary arteriosclerosis, and interstitial fibrosis. Conclusions —HCM in this family of Maine coon cats closely resembles the human form of FHCM and should prove a valuable tool for studying the gross, cellular, and molecular pathophysiology of the disease. }, number={24}, journal={Circulation}, author={Kittleson, M.D. and Meurs, K.M. and Munro, M. and Kittleson, J.A. and Liu, Si-Kwang and Pion, P.D. and Towbin, J.A.}, year={1999}, month={Jun}, pages={3172–3180} } @article{meurs_spier_miller_lehmkuhl_towbin_1999, title={Familial Ventricular Arrhythmias in Boxers}, volume={13}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.1999.tb01460.x}, DOI={10.1111/j.1939-1676.1999.tb01460.x}, abstractNote={The purposes of this study were to evaluate families of Boxers with ventricular arrhythmias to determine whether this disorder is a familial trait and, if so, to determine the mode of inheritance. Eighty‐two Boxers were evaluated by physical examination, electrocardiogram, echocardiogram, and 24‐hour ambulatory electrocardiogram. Dogs were considered affected if at least 50 premature ventricular complexes (PVCs) were observed during a 24‐hour period. All dogs were at least 6 years of age at evaluation. Complete cardiovascular examinations were performed on dogs from 6 extended families. The 2 most complete pedigrees were used to determine the pattern of inheritance. The number of PVCs observed during a 24‐hour period in affected dogs ranged from 112 to 4,894 (mean ± SD, median; 1,309 ± 2,609, 1,017). The number of PVCs observed during a 24‐hour period in the unaffected dogs ranged from 0 to 16 (7 ± 10, 12). Pedigree evaluation was performed to determine pattern of inheritance. An autosomal dominant pattern was determined to be most likely because a sex predisposition was not observed, affected individuals were observed in every generation, and 2 affected individuals produced unaffected offspring. We conclude that familial ventricular arrhythmias is inherited as an autosomal dominant trait in some Boxers.}, number={5}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Meurs, Kathryn M. and Spier, Alan W. and Miller, Matthew W. and Lehmkuhl, Linda and Towbin, Jeffrey A.}, year={1999}, month={Sep}, pages={437–439} } @article{meurs_anthony_slater_miller_1998, title={Chronic Trypanosoma cruzi infection in dogs: 11 cases (1987–1996)}, volume={213}, number={4}, journal={Journal of the American Veterinary Medical Association}, author={Meurs, K.M. and Anthony, M.A. and Slater, M. and Miller, M.W.}, year={1998}, pages={497–500} } @article{meurs_1998, title={Insights into the Hereditability of Canine Cardiomyopathy}, volume={28}, ISSN={0195-5616}, url={http://dx.doi.org/10.1016/s0195-5616(98)50131-3}, DOI={10.1016/s0195-5616(98)50131-3}, abstractNote={There is evidence for a genetic etiology of dilated cardiomyopathy in at least two breeds, the Doberman pinscher and the Boxer dog. Significant effort toward determining a genetic etiology in these breeds will depend on careful characterization of the disease, determination of criteria for diagnosing asymptomatic affected individuals, determination of a pattern of inheritance, and, eventually, molecular evaluation of the specific gene.}, number={6}, journal={Veterinary Clinics of North America: Small Animal Practice}, publisher={Elsevier BV}, author={Meurs, Kathryn M.}, year={1998}, month={Nov}, pages={1449–1457} } @article{atkins_defrancesco_miller_meurs_keene_1998, title={Prevalence of heartworm infection in cats with signs of cardiorespiratory abnormalities}, volume={212}, number={4}, journal={Journal of the American Veterinary Medical Association}, author={Atkins, C.E. and DeFrancesco, T. and Miller, M.W. and Meurs, K.M. and Keene, B.}, year={1998}, month={Feb}, pages={517–520} } @article{meurs_miller_hanson_honnas_1997, title={Tricuspid valve atresia with main pulmonary artery atresia in an Arabian foal}, volume={29}, DOI={10.1111/j.2042-3306.1997.tb01661.x}, abstractNote={Equine Veterinary JournalVolume 29, Issue 2 p. 160-162 Tricuspid valve atresia with main pulmonary artery atresia in an Arabian foal K. M. MEURS, K. M. MEURS Departments of Small Animal Medicine and Surgery, University College of Veterinary Medicine College Station, Texas 77843-4474, USA.Search for more papers by this authorM. W. MILLER, M. W. MILLER Departments of Small Animal Medicine and Surgery, University College of Veterinary Medicine College Station, Texas 77843-4474, USA.Search for more papers by this authorC. HANSON, C. HANSON Large Animal Medicine and Surgery, Texas A & M University College of Veterinary Medicine College Station, Texas 77843-4474, USA.Search for more papers by this authorC. HONNAS, C. HONNAS Large Animal Medicine and Surgery, Texas A & M University College of Veterinary Medicine College Station, Texas 77843-4474, USA.Search for more papers by this author K. M. MEURS, K. M. MEURS Departments of Small Animal Medicine and Surgery, University College of Veterinary Medicine College Station, Texas 77843-4474, USA.Search for more papers by this authorM. W. MILLER, M. W. MILLER Departments of Small Animal Medicine and Surgery, University College of Veterinary Medicine College Station, Texas 77843-4474, USA.Search for more papers by this authorC. HANSON, C. HANSON Large Animal Medicine and Surgery, Texas A & M University College of Veterinary Medicine College Station, Texas 77843-4474, USA.Search for more papers by this authorC. HONNAS, C. HONNAS Large Animal Medicine and Surgery, Texas A & M University College of Veterinary Medicine College Station, Texas 77843-4474, USA.Search for more papers by this author First published: 23 April 2010 https://doi.org/10.1111/j.2042-3306.1997.tb01661.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 Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References Bayly, W., Reed, S., Leathers, C., Brown, C., Traub, J., Paradis, M. and Palmer, G. (1982) Multiple congenital heart anomalies in five Arabian foals. J. Am. vet. med. Ass. 181, 684–689. 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Path. 19, 160–168. 10.1177/030098588201900207 CASPubMedWeb of Science®Google Scholar Citing Literature Volume29, Issue2March 1997Pages 160-162 ReferencesRelatedInformation}, number={2}, journal={Equine Veterinary Journal}, author={Meurs, K.M. and Miller, M.W. and Hanson, C. and Honnas, C.}, year={1997}, month={Mar}, pages={160–162} } @article{meurs_miller_slater_1996, title={Comparison of the indirect oscillometric and direct arterial methods for blood pressure measurements in anesthetized dogs}, volume={32}, DOI={10.5326/15473317-32-6-471}, abstractNote={The indirect oscillometric method of blood pressure measurement was compared to the direct arterial puncture method in 15 anesthetized dogs, divided into three weight groups, undergoing a variety of surgical procedures. The objectives of this study were to determine the accuracy of the indirect oscillometric method at a single point in time and when sequential values were averaged. Additionally, the ability to detect systemic hypotension (i.e., mean systemic arterial pressure less than 60 mmHg) was evaluated. The method had the highest correlation coefficient (r of 0.8) when five sequential values were averaged and compared, and it appeared to be sensitive (100%) and specific (91%) for detecting hypotension.}, number={6}, journal={Journal of the American Animal Hospital Association}, author={Meurs, K.M. and Miller, M.W. and Slater, M.}, year={1996}, pages={471–475} } @inbook{meurs_1996, place={Philadelphia}, edition={3rd}, title={Myocardial Disease}, booktitle={Handbook of Small Animal Practice}, publisher={WB Saunders}, author={Meurs, K.M.}, year={1996}, pages={560–568} } @inbook{meurs_miller_helman_1995, place={Philadelphia}, title={Canine Chagas' Myocarditis}, booktitle={Current Veterinary Therapy (Small Animal Practice) XII}, publisher={WB Saunders}, author={Meurs, K.M. and Miller, M.W. and Helman, R.G.}, year={1995}, pages={850–853} } @article{glaze_meurs_1995, title={Cardiovascular consequences of feline hyperthyroidism}, volume={16}, journal={Veterinary Technician}, author={Glaze, K. and Meurs, K.M.}, year={1995}, pages={23–26} } @article{meurs_miller_1995, title={ECG of the Month}, volume={206}, journal={Journal of the American Veterinary Medical Association}, author={Meurs, K.M. and Miller, M.W.}, year={1995}, pages={957–959} } @inbook{meurs_breitschwerdt_1995, place={Philadelphia}, title={Zinc Toxicosis}, booktitle={Current Veterinary Therapy (Small Animal Practice) XII}, publisher={WB Saunders}, author={Meurs, K.M. and Breitschwerdt, E.B.}, year={1995}, pages={238–240} } @inbook{meurs_1995, place={Baltimore}, title={Zinc toxicity}, booktitle={Five Minute Veterinary Consult}, publisher={Williams & Wilkens}, author={Meurs, K.M.}, year={1995}, pages={1164} } @article{meurs_atkins_khoo_keene_1994, title={Aberrant migration of toxocara larva as a cause of myocarditis in the dog}, volume={30}, number={6}, journal={Journal of the American Animal Hospital Association}, author={Meurs, K.M. and Atkins, C.E. and Khoo, L. and Keene, B.}, year={1994}, pages={580–582} } @article{meurs_miller_mackie_mathison_1994, title={Syncope associated with cardiac lymphoma in a cat}, volume={30}, journal={Journal of the American Animal Hospital Association}, author={Meurs, K.M. and Miller, M.W. and Mackie, J. and Mathison, P.}, year={1994}, pages={583–585} } @article{fossum_miller_rogers_bonagura_meurs_1993, title={Chylothorax associated with right-sided heart failure in five cats}, volume={204}, 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={1993}, month={Dec}, pages={84–89} } @article{meurs_miller_1993, title={ECG of the Month}, volume={203}, journal={Journal of the American Veterinary Medical Association}, author={Meurs, K.M. and Miller, M.W.}, year={1993}, pages={649–650} } @article{sinclair_meurs_1992, title={Challenging cases in internal medicine - Beagle polyarteritis}, volume={87}, journal={Veterinary Medicine}, author={Sinclair, L. and Meurs, K.M.}, year={1992}, pages={986–990} } @article{meurs_breitschwerdt_baty_1991, title={Postsurgical mortality secondary to zinc toxicity in dogs}, volume={33}, number={6}, journal={Veterinary and Human Toxicology}, author={Meurs, K. M. and Breitschwerdt, E. B. and Baty, C. J.}, year={1991}, pages={579} } @article{meurs_breitschwerdt_baty_young_1991, title={Postsurgical mortality secondary to zinc toxicity in dogs}, volume={33}, number={6}, journal={Veterinary and Human Toxicology}, author={Meurs, K.M. and Breitschwerdt, E.B. and Baty, C.J. and Young, M.E.}, year={1991}, month={Dec}, pages={579–583} } @article{friedenberg_meurs_mackay, title={Evaluation of artificial selection in Standard Poodles using whole-genome sequencing}, volume={27}, number={11-12}, journal={Mammalian Genome}, author={Friedenberg, S. G. and Meurs, K. M. and Mackay, T. F. C.}, pages={599–609} }