@article{rivas_tan_shaverdian_nguyen_wouters_stern_li_2024, title={A novel <i>ITGA2B</i> double cytosine frameshift variant (c.1986_1987insCC) leads to Glanzmann&apos;s thrombasthenia in a cat}, volume={3}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.17030}, DOI={10.1111/jvim.17030}, abstractNote={AbstractBackgroundGlanzmann's thrombasthenia (GT) is a congenital platelet disorder affecting approximately 1:1 000 000 people globally and characterized by impaired platelet aggregation and clot retraction. Autosomal recessive, loss‐of‐function, variants in ITGA2B or ITGB3 of the αIIbβ3 receptor cause the disease in humans. A cat affected by Glanzmann's and macrothrombocytopenia was presented to the UC Davis VMTH.Hypothesis/ObjectivesSevere thrombopathia in this cat has an underlying genetic etiology.AnimalsA single affected patient, 2 age‐matched clinically healthy controls, and a geriatric population (n = 20) of normal cats.MethodsPhysical examination and clinical pathology tests were performed on the patient. Flow cytometry and platelet aggregometry analyses for patient phenotyping were performed. Patient and validation cohort gDNA samples were extracted for Sanger sequencing of a previously identified ITGA2B (c.1986delC) variant. Reverse transcriptase PCR was performed on patient and healthy control PRP samples to verify ITGA2B variant consequence.ResultsA novel c.1986_1987insCC autosomal recessive variant in ITGA2B was identified. This variant was absent in a population of 194 unrelated cats spanning 44 different breeds. Complete loss of ITGA2B transcript and protein expression was verified by RT‐PCR and flow cytometry, explaining the underlying etiology of GT, and likely macrothrombocytopenia, in this cat.Conclusions and Clinical ImportanceThis study emphasizes the role of precision medicine in cardiovascular disease of cats and identified yet another variant that may be of utility for screening in the feline population. This study provides a small‐volume, standardized, successful protocol for adequate platelet RNA isolation and subsequent molecular assessment of gene expression in cats.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Rivas, Victor N. and Tan, Avalene W. K. and Shaverdian, Meg and Nguyen, Nghi P. and Wouters, Jalena R. and Stern, Joshua A. and Li, Ronald H. L.}, year={2024}, month={Mar} }
 @article{rivas_crofton_jauregui_wouters_yang_wittenburg_kaplan_hwee_murphy_morgan_et al._2024, title={Cardiac myosin inhibitor, CK-586, minimally reduces systolic function and ameliorates obstruction in feline hypertrophic cardiomyopathy}, volume={14}, ISSN={["2045-2322"]}, url={http://dx.doi.org/10.1038/s41598-024-62840-3}, DOI={10.1038/s41598-024-62840-3}, abstractNote={Abstract Hypertrophic cardiomyopathy (HCM) remains the most common cardiomyopathy in humans and cats with few preclinical pharmacologic interventional studies. Small-molecule sarcomere inhibitors are promising novel therapeutics for the management of obstructive HCM (oHCM) patients and have shown efficacy in left ventricular outflow tract obstruction (LVOTO) relief. The objective of this study was to explore the 6-, 24-, and 48-hour (h) pharmacodynamic effects of the cardiac myosin inhibitor, CK-586, in six purpose-bred cats with naturally occurring oHCM. A blinded, randomized, five-treatment group, crossover preclinical trial was conducted to assess the pharmacodynamic effects of CK-586 in this oHCM model. Dose assessments and select echocardiographic variables were assessed five times over a 48-h period. Treatment with oral CK-586 safely ameliorated LVOTO in oHCM cats. CK-586 treatment dose-dependently eliminated obstruction (reduced LVOTOmaxPG), increased measures of systolic chamber size (LVIDs Sx), and decreased select measures of heart function (LV FS% and LV EF%) in the absence of impact on heart rate. At all tested doses, a single oral CK-586 dose resulted in improved or resolved LVOTO with well-tolerated, dose-dependent, reductions in LV systolic function. The results from this study pave the way for the potential use of CK-586 in both the veterinary and human clinical setting.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Rivas, Victor N. and Crofton, Amanda E. and Jauregui, Carina E. and Wouters, Jalena R. and Yang, Betty S. and Wittenburg, Luke A. and Kaplan, Joanna L. and Hwee, Darren T. and Murphy, Anne N. and Morgan, Bradley P. and et al.}, year={2024}, month={May} }
 @article{pypendop_rivas_bueno_chohan_barter_stern_2024, title={Correlation, agreement and concordance of cardiac output estimated by transthoracic ultrasound and transesophageal Doppler with pulmonary artery thermodilution in anesthetized cats}, volume={51}, ISSN={["1467-2995"]}, url={https://doi.org/10.1016/j.vaa.2024.08.006}, DOI={10.1016/j.vaa.2024.08.006}, abstractNote={To characterize the correlation, agreement and concordance of cardiac output (CO) measured with transthoracic ultrasound and the correlation and concordance of aortic blood flow (ABF) minute distance (MD) measured by transesophageal Doppler with CO measured by pulmonary artery thermodilution (PATD) in cats.}, number={6}, journal={VETERINARY ANAESTHESIA AND ANALGESIA}, author={Pypendop, Bruno H. and Rivas, Victor N. and Bueno, Melissa Couto and Chohan, Amandeep S. and Barter, Linda S. and Stern, Joshua A.}, year={2024}, pages={641–649} }
 @article{rosati_jandrey_stern_nguyen_li_2024, title={Evaluation of clopidogrel response in healthy cats using a novel viscoelastic test and thromboelastography}, volume={11}, ISSN={["2297-1769"]}, url={https://europepmc.org/articles/PMC11217344}, DOI={10.3389/fvets.2024.1371781}, abstractNote={Introduction Cats with cardiomyopathy face an increased risk of arterial thromboembolism (ATE). Although clopidogrel is frequently utilized to mitigate this risk, feline responses to this therapy exhibit variability. This study evaluated 2 viscoelastic devices, thromboelastography (TEG) and Viscoelastic Coagulation Monitor (VCM), for monitoring clopidogrel in cats in comparison to light transmission aggregometry (LTA). Methods Twenty-eight healthy cats received clopidogrel for 7 days. Blood was collected at baseline and after treatment for analysis by TEG, VCM, and LTA. Results On LTA, maximum amplitude, slope, and area under the curve (AUC) significantly decreased after treatment ( p < 0.0001). On VCM, maximum clot firmness (MCF) significantly increased after treatment ( p = 0.002). On TEG, R-time significantly prolonged ( p = 0.024), while K and alpha angle significantly changed ( p = 0.0002 and p = 0.0014, respectively). There was a moderate negative correlation between TEG R-time and LTA AUC ( r = −0.39, p = 0.042). Eight cats were identified as non-responders to clopidogrel. Of the 8 non-responders, 6 (75%) had shortened R time after treatment. VCM appeared to be less discriminatory in identifying non-responders. Discussion LTA remained the gold standard of monitoring clopidogrel treatment in cats. Unexpected changes on VCM and TEG were likely related to high interindividual and assay variability and increased sensitivity of feline platelets. R-time on TEG may have potential utility for point-of-care monitoring of clopidogrel response in cats.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Rosati, Tommaso and Jandrey, Karl E. and Stern, Joshua A. and Nguyen, Nghi and Li, Ronald H. L.}, year={2024}, month={Jun} }
 @article{duler_visser_nguyen_johnson_stern_li_2024, title={Platelet hyperresponsiveness and increased platelet-neutrophil aggregates in dogs with myxomatous mitral valve disease and pulmonary hypertension}, volume={5}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.17067}, DOI={10.1111/jvim.17067}, abstractNote={Abstract Background Pulmonary hypertension (PH) in dogs with myxomatous mitral valve disease (MMVD) is caused by increased pulmonary venous pressure. Thrombosis, vascular remodeling, and vasoconstriction mediated by platelets could exacerbate PH. Hypothesis Dogs with PH will exhibit a hypercoagulable state, characterized by increased platelet activation, platelet‐leukocyte, and platelet‐neutrophil aggregate formation. Animals Eleven dogs (≥3.5 kg) diagnosed with MMVD and PH and 10 dogs with MMVD lacking PH. Methods Prospective cohort ex vivo study. All dogs underwent echocardiographic examination, CBC, 3‐view thoracic radiographs, and heartworm antigen testing. Severity of PH and MMVD were assessed by echocardiography. Viscoelastic monitoring of coagulation was assessed using thromboelastography (TEG). Platelet activation and platelet‐leukocyte/platelet‐neutrophil interactions were assessed using flow cytometry. Plasma serotonin concentrations were measured by ELISA. Results Unstimulated platelets from dogs with MMVD and PH expressed more surface P‐selectin than MMVD controls ( P = .03). Platelets from dogs with MMVD and PH had persistent activation in response to agonists. The number of platelet‐leukocyte aggregates was higher in dogs with MMVD and PH compared with MMVD controls ( P = .01). Ex vivo stimulation of whole blood resulted in higher numbers of platelet‐neutrophil aggregates in dogs with MMVD and PH ( P = .01). Assessment of hypercoagulability based on TEG or plasma serotonin concentrations did not differ between groups. Conclusion and Clinical Importance Platelet hyperresponsiveness and increased platelet‐neutrophil interaction occur in dogs with MMVD and PH, suggesting that platelets play a role of in the pathogenesis of PH. Clinical benefits of antiplatelet drugs in dogs with MMVD and PH require further investigation.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Duler, Laetitia and Visser, Lance and Nguyen, Nghi and Johnson, Lynelle R. and Stern, Joshua A. and Li, Ronald H. L.}, year={2024}, month={May} }
 @article{ali_perera_laird_batorsky_maron_rivas_stern_harris_chin_2025, title={Single Cell Transcriptomic Profiling of MYBPC3 ‐Associated Hypertrophic Cardiomyopathy Across Species Reveals Conservation of Biological Process But Not Gene Expression}, url={https://doi.org/10.1161/JAHA.124.035780}, DOI={10.1161/JAHA.124.035780}, abstractNote={Background Hypertrophic cardiomyopathy (HCM) is a common heritable heart disease where the most frequently associated mutations occur in the myosin‐binding protein C ( MYBPC3 ) sarcomere‐associated gene. HCM is also a common veterinary clinical problem in certain cat breeds such as Maine Coons and Ragdolls, also most associated with mutations in MYBPC3 . Mouse models of HCM in which Mybpc3 mutations are introduced recapitulate some, but not all, features of human HCM. Methods and Results To elucidate the common and distinctive pathological pathways across species and foster a greater understanding of the concordance of mouse HCM models to clinical mybpc3 ‐associated HCM, we generated single nuclei RNA‐sequencing data sets from feline, human, and murine heart tissue carrying MYBPC3 variants. Numerous genes were differentially expressed between mutation positive and mutation negative cell types within each species, identified using the model‐based analysis of single‐cell transcriptomics algorithm. Gene Ontology enrichment analysis of differentially expressed genes in cardiomyocytes across species revealed alterations in genes involved in muscle development, muscle contraction, muscle hypertrophy, regulation of sarcoplasmic calcium release, ATP metabolic process, and oxidative phosphorylation. Conclusions These common biological processes across species are consistent with known phenotypic aspects of HCM such as hypertrophy, hypercontractility, diastolic dysfunction, and altered energy metabolism. Surprisingly, among conserved biological processes within cardiomyocytes across species, the individual genes driving the biological processes were distinct. This work to identify common and species‐specific disease‐promoting pathway differences will allow development of targeted therapies for both human and veterinary application and will facilitate an understanding of the idiosyncrasies of mouse models.}, journal={Journal of the American Heart Association}, author={Ali, Samia A. and Perera, Gayani and Laird, Jason and Batorsky, Rebecca and Maron, Martin S. and Rivas, Victor N. and Stern, Joshua A. and Harris, Samantha and Chin, Michael T.}, year={2025}, month={Jan} }
 @article{stern_2024, title={Training the next generation of veterinary academic leaders}, volume={85}, ISSN={["1943-5681"]}, url={https://doi.org/10.2460/ajvr.24.06.0175}, DOI={10.2460/ajvr.24.06.0175}, number={8}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Stern, Joshua A.}, year={2024}, month={Aug} }
 @article{rivas_vandewege_ueda_kaplan_reader_roberts_stern_2024, title={Transcriptomic and genetic profiling in a spontaneous non-human primate model of hypertrophic cardiomyopathy and sudden cardiac death}, volume={14}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-024-82770-4}, abstractNote={Hypertrophic cardiomyopathy (HCM) afflicts humans, cats, pigs, and rhesus macaques. Disease sequelae include congestive heart failure, thromboembolism, and sudden cardiac death (SCD). Sarcomeric mutations explain some human and cat cases, however, the molecular basis in rhesus macaques remains unknown. RNA-Seq of the LV tissues of five HCM-affected and seven healthy control rhesus macaques was employed for differential transcriptomic analyses. DNA from 15 severely HCM-affected and 21 healthy geriatric rhesus macaques were selected for whole-genome sequencing. A genome-wide association study (GWAS) of disease status and SCD outcome was performed. 614 down- and 1,065 upregulated differentially expressed genes (DEGs) were identified between groups. The top DEG (MAFF) was overexpressed in affected animals (log2FoldChange = 4.71; PAdjusted-value = 1.14E-133). Channelopathy-associated enriched terms were identified in ~ 57% of downregulated DEGs providing transcriptomic evidence of hypertrophic and arrhythmic disease processes. For GWAS, no putative variant withstood segregation. Polygenic modeling analysis resulted in poor prediction power and burden testing could not explain HCM by an association of multiple variants in any gene. Neither single nor compound genetic variant(s), or identified polygenic profile, suggest complex genotype–phenotype interactions in rhesus macaques. Brought forth is an established dataset of robustly phenotyped rhesus macaques as an open-access resource for future cardiovascular disease genetic studies.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Rivas, Victor N. and Vandewege, Michael W. and Ueda, Yu and Kaplan, Joanna L. and Reader, Jrachel and Roberts, Jeffrey A. and Stern, Joshua A.}, year={2024}, month={Dec} }
 @article{rebhun_york_de graaf_yoon_batcher_luker_ryan_peyton_kent_stern_et al._2023, title={A variant in the 5'UTR of ERBB4 is associated with lifespan in Golden Retrievers}, volume={10}, url={https://link.springer.com/content/pdf/10.1007/s11357-023-00968-2.pdf}, DOI={10.1007/s11357-023-00968-2}, abstractNote={Abstract Genome-wide association studies (GWAS) in long-lived human populations have led to identification of variants associated with Alzheimer’s disease and cardiovascular disease, the latter being the most common cause of mortality in people worldwide. In contrast, naturally occurring cancer represents the leading cause of death in pet dogs, and specific breeds like the Golden Retriever (GR) carry up to a 65% cancer-related death rate. We hypothesized that GWAS of long-lived GRs might lead to the identification of genetic variants capable of modifying longevity within this cancer-predisposed breed. A GWAS was performed comparing GR dogs ≥ 14 years to dogs dying prior to age 12 which revealed a significant association to ERBB4 , the only member of the epidermal growth factor receptor family capable of serving as both a tumor suppressor gene and an oncogene. No coding variants were identified, however, distinct haplotypes in the 5′UTR were associated with reduced lifespan in two separate populations of GR dogs. When all GR dogs were analyzed together ( n = 304), the presence of haplotype 3 was associated with shorter survival (11.8 years vs. 12.8 years, p = 0.024). GRs homozygous for haplotype 3 had the shortest survival, and GRs homozygous for haplotype 1 had the longest survival (11.6 years vs. 13.5 years, p = 0.0008). Sub-analyses revealed that the difference in lifespan for GRs carrying at least 1 copy of haplotype 3 was specific to female dogs ( p = 0.009), whereas survival remained significantly different in both male and female GRs homozygous for haplotype 1 or haplotype 3 ( p = 0.026 and p = 0.009, respectively). Taken together, these findings implicate a potential role for ERBB4 in GR longevity and provide evidence that within-breed canine lifespan studies could serve as a mechanism to identify favorable or disease-modifying variants important to the axis of aging and cancer.}, journal={GeroScience}, author={Rebhun, Robert B and York, Daniel and De Graaf, Flora M D and Yoon, Paula and Batcher, Kevin L and Luker, Madison E and Ryan, Stephanie and Peyton, Jamie and Kent, Michael S and Stern, Joshua A and et al.}, year={2023} }
 @article{li_fabella_nguyen_kaplan_ontiveros_stern_2023, title={Circulating neutrophil extracellular traps in cats with hypertrophic cardiomyopathy and cardiogenic arterial thromboembolism}, volume={37}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/jvim.16676}, DOI={10.1111/jvim.16676}, abstractNote={AbstractBackgroundCats with hypertrophic cardiomyopathy (HCM) are at risk of cardiogenic arterial thromboembolism (CATE). Neutrophil extracellular traps (NETs) may be a potential biomarker and therapeutic target for cardiomyopathy in cats.Hypothesis/ObjectivesCharacterize NETs in cats with HCM or CATE. We hypothesized that circulating NETs assessed in the form of cell‐free DNA (cfDNA) and citrullinated histone H3 (citH3) are increased in cats with HCM and CATE and associated with reported predisposing factors for thrombus formation.AnimalsEighty‐five cats including client‐owned cats with HCM and CATE and staff‐ and student‐owned clinically healthy cats without HCM.MethodsAfter echocardiographic evaluations, NETs were measured as cfDNA and citH3.ResultsCats with CATE had significant increases in cfDNA (11.2 ng/μL; interquartile range [IQR], 8.1 to 29.6) compared to those without HCM (8.2 ng/μL; IQR, 5.7 to 11.7 μL; P = .01) and were responsible for 75% to 83% of cases with cfDNA fragments sized 100 to 2000 base pairs. Citrullinated histone 3, detected in 52% of cats with HCM (31.1 ng/mL; IQR, 16.9 to 29.8), was significantly lower than in those with CATE (48.2 ng/mL; IQR, 34.2 to 60.2; P = .007). The citH3 concentrations correlated significantly with reported risk factors of CATE, such as left atrial auricular velocity.Conclusions and Clinical ImportanceNeutrophil extracellualr traps, especially citH3, are increased in cats with HCM and CATE. They may serve as a novel therapeutic target and biomarker of thrombosis in cats with HCM.}, number={2}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Li, Ronald H. L. and Fabella, Arianne and Nguyen, Nghi and Kaplan, Joanna L. and Ontiveros, Eric and Stern, Joshua A.}, year={2023}, month={Mar}, pages={490–502} }
 @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://doi.org/10.2460/javma.23.04.0187}, 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{sharpe_oldach_rivas_kaplan_walker_kovacs_hwee_cremin_morgan_malik_et al._2023, title={Effects of Aficamten on cardiac contractility in a feline translational model of hypertrophic cardiomyopathy}, volume={13}, url={https://europepmc.org/articles/PMC9807554}, DOI={10.1038/s41598-022-26630-z}, abstractNote={AbstractHypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease in humans and cats and lacks efficacious pharmacologic interventions in the preclinical phase of disease. LV outflow tract obstruction (LVOTO) is commonly observed in HCM-affected patients and is a primary driver of heart failure symptoms and reduced quality of life. Novel small-molecule cardiac myosin inhibitors target actin-myosin interactions to alleviate overactive protein interactions. A prospective, randomized, controlled cross-over study was performed to evaluate pharmacodynamic effects of two doses (0.3 and 1 mg/kg) of a next-in-class cardiac myosin inhibitor,aficamten(CK-3773274, CK-274), on cardiac function in cats with the A31PMYBPC3mutation and oHCM. Dose-dependent reductions in LV systolic function, LVOT pressure gradient, and isovolumetric relaxation times compared to baseline were observed. Promising beneficial effects of reduced systolic function warrant further studies of this next-in-class therapeutic to evaluate the benefit of long-term administration in this patient population.}, number={1}, journal={Scientific reports}, author={Sharpe, Ashley N and Oldach, Maureen S and Rivas, Victor N and Kaplan, Joanna L and Walker, Ashley L and Kovacs, Samantha L and Hwee, Darren T and Cremin, Peadar and Morgan, Bradley P and Malik, Fady I and et al.}, year={2023}, pages={32} }
 @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{stern_2023, title={Exciting Advancements and Compelling Future Directions in Companion Animal Cardiology}, volume={53}, ISSN={["1878-1306"]}, url={https://doi.org/10.1016/j.cvsm.2023.08.009}, DOI={10.1016/j.cvsm.2023.08.009}, number={6}, journal={VETERINARY CLINICS OF NORTH AMERICA-SMALL ANIMAL PRACTICE}, author={Stern, Joshua A.}, year={2023}, month={Nov} }
 @article{stern_rivas_kaplan_ueda_oldach_ontiveros_kooiker_dijk_harris_2023, title={Hypertrophic cardiomyopathy in purpose-bred cats with the A31P mutation in cardiac myosin binding protein-C}, volume={13}, ISSN={["2045-2322"]}, url={https://europepmc.org/articles/PMC10293195}, DOI={10.1038/s41598-023-36932-5}, abstractNote={AbstractWe sought to establish a large animal model of inherited hypertrophic cardiomyopathy (HCM) with sufficient disease severity and early penetrance for identification of novel therapeutic strategies. HCM is the most common inherited cardiac disorder affecting 1 in 250–500 people, yet few therapies for its treatment or prevention are available. A research colony of purpose-bred cats carrying the A31P mutation in MYBPC3 was founded using sperm from a single heterozygous male cat. Cardiac function in four generations was assessed by periodic echocardiography and measurement of blood biomarkers. Results showed that HCM penetrance was age-dependent, and that penetrance occurred earlier and was more severe in successive generations, especially in homozygotes. Homozygosity was also associated with progression from preclinical to clinical disease. A31P homozygous cats represent a heritable model of HCM with early disease penetrance and a severe phenotype necessary for interventional studies aimed at altering disease progression. The occurrence of a more severe phenotype in later generations of cats, and the occasional occurrence of HCM in wildtype cats suggests the presence of at least one gene modifier or a second causal variant in this research colony that exacerbates the HCM phenotype when inherited in combination with the A31P mutation.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Stern, Joshua A. and Rivas, Victor N. and Kaplan, Joanna L. and Ueda, Yu and Oldach, Maureen S. and Ontiveros, Eric S. and Kooiker, Kristina B. and Dijk, Sabine J. and Harris, Samantha P.}, year={2023}, month={Jun} }
 @article{rivas_kaplan_kennedy_fitzgerald_crofton_farrell_grubb_jauregui_grigorean_choi_et al._2023, title={Multi-Omic, Histopathologic, and Clinicopathologic Effects of Once-Weekly Oral Rapamycin in a Naturally Occurring Feline Model of Hypertrophic Cardiomyopathy: A Pilot Study}, volume={13}, ISSN={["2076-2615"]}, url={https://europepmc.org/articles/PMC10603660}, DOI={10.3390/ani13203184}, abstractNote={Hypertrophic cardiomyopathy (HCM) remains the single most common cardiomyopathy in cats, with a staggering prevalence as high as 15%. To date, little to no direct therapeutical intervention for HCM exists for veterinary patients. A previous study aimed to evaluate the effects of delayed-release (DR) rapamycin dosing in a client-owned population of subclinical, non-obstructive, HCM-affected cats and reported that the drug was well tolerated and resulted in beneficial LV remodeling. However, the precise effects of rapamycin in the hypertrophied myocardium remain unknown. Using a feline research colony with naturally occurring hereditary HCM (n = 9), we embarked on the first-ever pilot study to examine the tissue-, urine-, and plasma-level proteomic and tissue-level transcriptomic effects of an intermittent low dose (0.15 mg/kg) and high dose (0.30 mg/kg) of DR oral rapamycin once weekly. Rapamycin remained safe and well tolerated in cats receiving both doses for eight weeks. Following repeated weekly dosing, transcriptomic differences between the low- and high-dose groups support dose-responsive suppressive effects on myocardial hypertrophy and stimulatory effects on autophagy. Differences in the myocardial proteome between treated and control cats suggest potential anti-coagulant/-thrombotic, cellular remodeling, and metabolic effects of the drug. The results of this study closely recapitulate what is observed in the human literature, and the use of rapamycin in the clinical setting as the first therapeutic agent with disease-modifying effects on HCM remains promising. The results of this study establish the need for future validation efforts that investigate the fine-scale relationship between rapamycin treatment and the most compelling gene expression and protein abundance differences reported here.}, number={20}, journal={ANIMALS}, author={Rivas, Victor N. and Kaplan, Joanna L. and Kennedy, Susan A. and Fitzgerald, Stuart and Crofton, Amanda E. and Farrell, Aisling and Grubb, Louise and Jauregui, Carina E. and Grigorean, Gabriela and Choi, Eunju and et al.}, year={2023}, month={Oct} }
 @article{bannasch_oertle_vo_batcher_stern_kaplan_li_madden_christen_leeb_et al._2023, title={Naturally occurring canine laminopathy leading to a dilated and fibrosing cardiomyopathy in the Nova Scotia Duck Tolling Retriever}, volume={13}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/s41598-023-46601-2}, DOI={10.1038/s41598-023-46601-2}, abstractNote={AbstractDilated cardiomyopathy (DCM) is characterized by decreased systolic function and dilation of one or both ventricles, often leading to heart failure or sudden death. Two 10-month-old sibling Nova Scotia Duck Tolling Retrievers (NSDTR) died acutely with evidence of dilated cardiomyopathy with myocardial fibrosis. Association analysis using two cases and 35 controls identified three candidate regions homozygous in the two cases. Whole genome sequencing identified a frameshift deletion in the LMNA gene (NC_049228.1:g.41688530del, NP_001274080:p.(Asp576ThrfsTer124)). Three retrospectively identified NSDTRs with sudden death before 2 years of age and severe myocardial fibrosis were also homozygous for the deletion. One 5 year old with sudden death and myocardial fibrosis was heterozygous for the deletion. This variant was not identified in 722 dogs of other breeds, nor was it identified to be homozygous in 784 NSDTR. LMNA codes for lamin A/C proteins, which are type V intermediate filaments that provide structural support to the nuclear membrane. In humans, LMNA variants can cause DCM with sudden death as well as diseases of striated muscles, lipodystrophy, neuropathies, and accelerated aging disorders. This frameshift deletion is predicted to affect processing of prelamin A into lamin A. Pedigree analysis in the NSDTR and functional evaluation of heterozygotes is consistent with a predominantly recessive mode of inheritance and possibly low penetrance in heterozygotes in contrast to people, where most pathogenic LMNA variants are dominantly inherited.}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Bannasch, Danika L. and Oertle, Danielle T. and Vo, Julia and Batcher, Kevin L. and Stern, Joshua A. and Kaplan, Joanna L. and Li, Ronald H. L. and Madden, Indiana E. and Christen, Matthias and Leeb, Tosso and et al.}, year={2023}, month={Nov}, pages={19077} }
 @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{vallender_hotchkiss_lewis_rogers_stern_peterson_ferguson_sayers_2023, title={Nonhuman primate genetic models for the study of rare diseases}, volume={18}, url={https://europepmc.org/articles/PMC9887761}, DOI={10.1186/s13023-023-02619-3}, abstractNote={Abstract Pre-clinical research and development relies heavily upon translationally valid models of disease. A major difficulty in understanding the biology of, and developing treatments for, rare disease is the lack of animal models. It is important that these models not only recapitulate the presentation of the disease in humans, but also that they share functionally equivalent underlying genetic causes. Nonhuman primates share physiological, anatomical, and behavioral similarities with humans resulting from close evolutionary relationships and high genetic homology. As the post-genomic era develops and next generation sequencing allows for the resequencing and screening of large populations of research animals, naturally occurring genetic variation in nonhuman primates with clinically relevant phenotypes is regularly emerging. Here we review nonhuman primate models of multiple rare genetic diseases with a focus on the similarities and differences in manifestation and etiologies across species. We discuss how these models are being developed and how they can offer new tools and opportunities for researchers interested in exploring novel therapeutics for these and other genetic diseases. Modeling human genetic diseases in translationally relevant nonhuman primates presents new prospects for development of therapeutics and a better understanding of rare diseases. The post-genomic era offers the opportunity for the discovery and further development of more models like those discussed here.}, number={1}, journal={Orphanet journal of rare diseases}, author={Vallender, Eric J and Hotchkiss, Charlotte E and Lewis, Anne D and Rogers, Jeffrey and Stern, Joshua A and Peterson, Samuel M and Ferguson, Betsy and Sayers, Ken}, year={2023}, pages={20} }
 @article{rivas_ueda_stern_2023, title={Sex-specific differences and predictors of echocardiographic measures of diastolic dysfunction in rhesus macaques (Macaca mulatta)}, volume={7}, ISSN={["1600-0684"]}, url={https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jmp.12662}, DOI={10.1111/jmp.12662}, abstractNote={AbstractBackgroundDiastolic dysfunction in humans is an age‐related process with an overrepresentation in women. In rhesus macaques (Macaca mulatta), the incidence and predictors of diastolic dysfunction have yet to be reported.MethodsData from routine echocardiographic evaluations on clinically healthy rhesus macaques was obtained and used for univariate, bivariate, hypothesis testing, and linear regression statistical analyses interrogating differences and predictors of diastolic function.ResultsRhesus macaques fully recapitulate previously reported human hemodynamic studies. Female monkeys display impaired diastology and are at an increased risk for developing diastolic dysfunction. Age, sex, and proxies of exercise activity are confirmed predictors for measures of diastolic dysfunction, regardless of specific pathogen‐free status.ConclusionsRhesus macaques share common sex‐ and age‐related echocardiographic findings as humans, therefore, serve as a valuable translational nonhuman primate model for future studies of diastolic dysfunction. These findings confirm the importance of sex‐ and age‐matching within future rhesus macaque cardiovascular research.}, journal={JOURNAL OF MEDICAL PRIMATOLOGY}, author={Rivas, Victor N. and Ueda, Yu and Stern, Joshua A.}, year={2023}, month={Jul} }
 @misc{crofton_kovacs_stern_2023, title={Subvalvular Aortic Stenosis: Learning From Human and Canine Clinical Research}, volume={14}, ISSN={["1923-2837"]}, url={https://doi.org/10.14740/cr1547}, DOI={10.14740/cr1547}, abstractNote={Subvalvular aortic stenosis (SAS) is the most common congenital heart disease (CHD) in dogs and is also prevalent in human children. A fibrous ridge below the aortic valve narrows the left ventricular outflow tract (LVOT) and increases blood flow velocity, leading to devastating side effects in diseased patients. Due to the similarities in presentation, anatomy, pathophysiology, cardiac development, genomics, and environment between humans and dogs, canine SAS patients represent a critical translational model of human SAS. Potential adverse outcomes of SAS include arrhythmias, left-sided congestive heart failure, endocarditis, exercise intolerance, syncope, and sudden cardiac death. The greatest divergence between canine and human SAS clinical research has been the standard of care regarding treatment of these outcomes, with pharmacological intervention dominating best practices in veterinary medicine and surgical intervention comprising the standard practice for human SAS patients. Regardless of the species, the field has yet to identify a treatment option to prevent disease progression or permanently remove the fibrous ridge, but historical leaps in SAS research support a continued translational approach as the most promising method for achieving this goal.}, number={5}, journal={CARDIOLOGY RESEARCH}, author={Crofton, Amanda E. and Kovacs, Samantha L. and Stern, Joshua A.}, year={2023}, month={Oct}, pages={319–333} }
 @article{lo_li_georges_nguyen_chen_stuhlmann_oldach_rivas_fousse_harris_et al._2023, title={Synergistic inhibitory effects of clopidogrel and rivaroxaban on platelet function and platelet‐dependent thrombin generation in cats}, volume={37}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/jvim.16727}, DOI={10.1111/jvim.16727}, abstractNote={AbstractBackgroundDual antithrombotic treatment (DAT) with clopidogrel and rivaroxaban sometimes is prescribed to cats with hypertrophic cardiomyopathy at risk of thromboembolism. To date, no studies have evaluated their combined effects on platelet function.Objectives/HypothesisEvaluate the safety of DAT in healthy cats and compare, ex vivo, platelet‐dependent thrombin generation and agonist‐induced platelet activation and aggregation in cats treated with clopidogrel, rivaroxaban, or DAT. We hypothesized that DAT would safely modulate agonist‐induced platelet activation and aggregation more effectively than single agent treatment.AnimalsNine apparently healthy 1‐year‐old cats selected from a research colony.MethodsUnblinded, nonrandomized ex vivo cross‐over study. All cats received 7 days of rivaroxaban (0.6 ± 0.1 mg/kg PO), clopidogrel (4.7 ± 0.8 mg/kg PO), or DAT with defined washout periods between treatments. Before and after each treatment, adenosine diphosphate (ADP)‐ and thrombin‐induced platelet P‐selectin expression was evaluated using flow cytometry to assess platelet activation. Platelet‐dependent thrombin generation was measured by fluorescence assay. Platelet aggregation was assessed using whole blood impedance platelet aggregometry.ResultsNo cats exhibited adverse effects. Of the 3 treatments, only DAT significantly decreased the number of activated platelets (P = .002), modulated platelet activation in response to thrombin (P = .01), dampened thrombin generation potential (P = .01), and delayed maximum reaction velocity (P = .004) in thrombin generation. Like clopidogrel, DAT inhibited ADP‐mediated platelet aggregation. However, rivaroxaban alone resulted in increased aggregation and activation in response to ADP.Conclusion and Clinical ImportanceTreatment combining clopidogrel and rivaroxaban (DAT) safely decreases platelet activation, platelet response to agonists, and thrombin generation in feline platelets more effectively than monotherapy with either clopidogrel or rivaroxaban.}, number={4}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Lo, Sara T. and Li, Ronald H. L. and Georges, Catherine J. and Nguyen, Nghi and Chen, Cheyenne K. and Stuhlmann, Claire and Oldach, Maureen Sigmund and Rivas, Victor Noel and Fousse, Samantha and Harris, Samantha P. and et al.}, year={2023}, month={May}, pages={1390–1400} }
 @article{kovacs_scansen_stern_2023, title={The Genetics of Canine Pulmonary Valve Stenosis.}, volume={53}, url={https://doi.org/10.1016/j.cvsm.2023.05.014}, DOI={10.1016/j.cvsm.2023.05.014}, number={6}, journal={The Veterinary clinics of North America. Small animal practice}, author={Kovacs, S and Scansen, BA and Stern, JA}, year={2023}, month={Jul}, pages={1379—1391} }
 @article{rivas_stern_ueda_2023, title={The Role of Personalized Medicine in Companion Animal Cardiology}, volume={53}, ISSN={["1878-1306"]}, url={https://doi.org/10.1016/j.cvsm.2023.05.016}, DOI={10.1016/j.cvsm.2023.05.016}, abstractNote={Cardiomyopathies remain one of the most common inherited cardiac diseases in both human and veterinary patients. To date, well over 100 mutated genes are known to cause cardiomyopathies in humans with only a handful known in cats and dogs. This review highlights the need and use of personalized one-health approaches to cardiovascular case management and advancement in pharmacogenetic-based therapy in veterinary medicine. Personalized medicine holds promise in understanding the molecular basis of disease and ultimately will unlock the next generation of targeted novel pharmaceuticals and aid in the reversal of detrimental effects at a molecular level.}, number={6}, journal={VETERINARY CLINICS OF NORTH AMERICA-SMALL ANIMAL PRACTICE}, author={Rivas, Victor N. and Stern, Joshua A. and Ueda, Yu}, year={2023}, month={Nov}, pages={1255–1276} }
 @article{walker_ueda_crofton_harris_stern_2022, title={Ambulatory electrocardiography, heart rate variability, and pharmacologic stress testing in cats with subclinical hypertrophic cardiomyopathy}, volume={12}, ISSN={["2045-2322"]}, url={https://europepmc.org/articles/PMC8817045}, DOI={10.1038/s41598-022-05999-x}, abstractNote={AbstractThe utility of ambulatory electrocardiography (AECG) to evaluate cats with subclinical hypertrophic cardiomyopathy (HCM) for arrhythmias and heart rate variability (HRV) is not well defined but may provide information regarding risk stratification. This prospective study used AECG to evaluate ectopy and HRV in subclinical HCM cats compared to healthy controls and is the first to implement a pharmacologic cardiac stress test. Twenty-three purpose-bred, Maine coon cross cats (16 HCM, 7 control) underwent 48-h of continuous AECG. Terbutaline (0.2–0.3 mg/kg) was administered orally at 24 and 36 h. Heart rate, ectopy frequency and complexity and HRV parameters, including standard deviation of normal R-R intervals (SDNN), were compared pre-terbutaline and post-terbutaline and across phenotype, genotype and sex. Genotype for an HCM-causative mutation was significantly associated with the frequency of supraventricular (P = 0.033) and ventricular (P = 0.026) ectopy across all cats. Seven HCM cats and zero healthy cats had a sinus arrhythmia. Mean heart rate was significantly higher post-terbutaline (p < 0.0001). HCM cats had significantly greater HRV compared to controls (SDNN: p = 0.0006). Male cats had significantly higher HRV (SDNN: p = 0.0001) and lower mean heart rates (p = 0.0001). HRV decreased post-terbutaline (SDNN: p = 0.0008) and changes in HRV observed between sexes were attenuated by terbutaline.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Walker, Ashley L. and Ueda, Yu and Crofton, Amanda E. and Harris, Samantha P. and Stern, Joshua A.}, year={2022}, month={Feb} }
 @article{edwards_kaplan_oldach_magdesian_louie_stern_berryhill_2022, title={Closure of a patent ductus arteriosus in a 2-week-old llama cria using an Amplatz canine duct occluder}, volume={63}, url={https://europepmc.org/articles/PMC9207981}, number={7}, journal={The Canadian veterinary journal = La revue veterinaire canadienne}, author={Edwards, Lisa A and Kaplan, Joanna L and Oldach, Maureen S and Magdesian, K Gary and Louie, Elizabeth Williams and Stern, Joshua A and Berryhill, Emily}, year={2022}, pages={706—710} }
 @article{kaplan_visser_gunther-harrington_ontiveros_wittenburg_palm_stern_2022, title={Effect of standard-dose and high-dose pimobendan on select indices of renal and cardiac function in dogs with American College of Veterinary Internal Medicine stage B2 myxomatous mitral valve disease}, volume={36}, url={https://europepmc.org/articles/PMC9708424}, DOI={10.1111/jvim.16537}, abstractNote={Abstract Background Pimobendan might have favorable effects on renal function but this has not been well‐studied in dogs with myxomatous mitral valve disease (MMVD). Objectives Determine the effects of standard‐dose (SD_pimo) and high‐dose pimobendan (HD_pimo) on glomerular filtration rate (GFR) and cardiac size and function in dogs with preclinical MMVD. Animals Thirty nonazotemic dogs with stage B2 MMVD. Methods Prospective, randomized, double‐blinded, placebo‐controlled clinical study. Dogs had an echocardiographic examination, assessment of GFR (iohexol clearance), N‐terminal probrain natriuretic peptide (NT‐proBNP), and quality of life (QOL) score at baseline and 7 to 10 days after placebo (n = 6), SD_pimo 0.2 to 0.3 mg/kg q12 (n = 12), or HD_pimo 0.5 to 0.6 mg/kg q12h (n = 12). Results No significant differences in GFR or QOL scores were detected between groups ( P .07). After HD_pimo, the mean [SD] percent change of NT_proBNP (−46.1 [20.2]%), left atrial volume (LAV; −27.1 [16.9]%), left ventricular end‐diastolic volume (EDV; −21.8 [15.0]%), and end‐systolic volume (ESV; −55.0 [20.7]%) were significantly different ( P .004) from placebo (0.5 [19.9]%, 1.3 [15.6]%, −0.2 [8.2]%, −7.3 [35.6]%, respectively) but not the percent change after SD_pimo (−36.6 [16.1]%, −22.7 [14.9]%, −16.7 [12.5]%, −41.6 [14.8]%, respectively; P > .05). After SD_pimo, percent change of NT_proBNP, LAV, EDV, and ESV were significantly different from placebo ( P < .05). Conclusions and Clinical Importance Results suggest that pimobendan (SD_pimo or HD_pimo) might not affect renal function in nonazotemic dogs with stage B2 MMVD. High‐dose pimobendan did not demonstrate advantages over SD_pimo within the constraints of our study.}, number={6}, journal={Journal of veterinary internal medicine}, author={Kaplan, Joanna L and Visser, Lance C and Gunther-Harrington, Catherine T and Ontiveros, Eric S and Wittenburg, Luke A and Palm, Carrie A and Stern, Joshua A}, year={2022}, pages={1892—1899} }
 @article{aller_guzman_stern_douglas_golsen_drazenovich_paul-murphy_2022, title={Evaluation of a Fluoroscopic Angiography Protocol in Hispaniolan Amazon Parrots (<i>Amazona ventralis</i>)}, volume={36}, url={https://doi.org/10.1647/21-00007}, DOI={10.1647/21-00007}, abstractNote={Fluoroscopic angiography evaluates the heart and vascular tree in real time and can be recorded for further diagnostic analysis and measurements. Although reports have been published of the use of fluoroscopic angiography in birds, this technique has not been evaluated in any avian species. The purpose of this study was to evaluate a fluoroscopic angiography protocol in 12 adult Hispaniolan Amazon parrots (Amazona ventralis). Under general anesthesia, the birds were positioned in right lateral (LAT) recumbency on a fluoroscopy table. A bolus of nonionic iodinated contrast agent was injected through a catheter inserted into the basilic or medial metatarsal vein during video acquisition. The same bolus was repeated to obtain the ventrodorsal (VD) view with the bird placed in dorsal recumbency. Eleven studies were performed. A total of 19 (10 VD, 9 LAT) continuous, real-time, fluoroscopic angiograms were successfully captured. The brachiocephalic trunk, aorta, pulmonary arteries, pulmonary veins, and caudal vena cava were visualized, and selected intraluminal measurements collected. The intraobserver and interobserver variability for 3 observers was calculated. Intraobserver agreement was found to be near perfect (intraclass correlation coefficient ≥0.95), whereas interobserver agreement was moderate to substantial (intraclass correlation coefficient ≥0.52). Coefficients of variation were excellent (VD 0.99, LAT 0.99) for intraobserver assessments and moderate (VD 0.72, LAT 0.52) for interobserver assessments. For the interobserver assessments, the VD projection measurements performed better than the LAT measurements. These results suggest that although there was some variation between different observers, relatively consistent vascular measurements could be obtained. The described fluoroscopic angiography protocol is a repeatable and reliable technique that could be useful for the diagnosis and monitoring of cardiovascular diseases in birds.}, number={2}, journal={Journal of avian medicine and surgery}, author={Aller, Theresa L and Guzman, David Sanchez-Migallon and Stern, Joshua A and Douglas, Jamie M and Golsen, Bryce M and Drazenovich, Tracy L and Paul-Murphy, Joanne}, year={2022}, pages={178—186} }
 @article{reagan_visser_epstein_stern_johnson_2022, title={Outcome and prognostic factors in infective endocarditis in dogs: 113 cases (2005-2020)}, volume={36}, url={https://europepmc.org/articles/PMC8965206}, DOI={10.1111/jvim.16380}, abstractNote={Factors associated with outcome in dogs diagnosed with infective endocarditis (IE) are not well characterized.Evaluate outcome and prognostic factors in dogs with IE.One hundred and thirteen dogs with IE.Medical records for dogs that fulfilled the modified Duke criteria between 2005 and 2020 were retrospectively reviewed. Signalment, preexisting conditions, clinicopathologic findings, treatment regimen, and outcomes were recorded. Univariate logistic regression was performed to identify categorical factors associated with mortality, and then multivariate analysis was performed.Dogs were categorized as survivors (n = 47), non-survivors (n = 57), or lost to follow-up (n = 9). Survival to discharge and at 1 month was documented in 79 (70%) of 113 and 56 (54%) of 104 dogs, respectively, with median survival time (MST) of 72 days. Risk factors associated with mortality included development of congestive heart failure (odds ratio [OR], 11.8; 95% confidence interval [CI], 1.4-97.8), thromboembolic events (OR, 5.7; 95% CI, 2.3-14.4), and acute kidney injury (OR, 6.2; 95% CI, 2.0-18.8). Administration of antithrombotic medications was associated with survival (OR, 0.35; 95% CI, 0.13-0.97). Dogs that were not treated with antithrombotics had MST of 92 days, whereas dogs treated with antithrombotics did not reach MST during the study period. The heart valves involved and etiologic agent identified did not correlate with outcome.Dogs with IE that had thromboembolic events, acute kidney injury, or congestive heart failure had higher risk of mortality. Administration of antithrombotics was associated with prolonged survival time.}, number={2}, journal={Journal of veterinary internal medicine}, author={Reagan, Krystle L and Visser, Lance C and Epstein, Steven E and Stern, Joshua A and Johnson, Lynelle R}, year={2022}, pages={429—440} }
 @article{sharpe_oldach_kaplan_rivas_kovacs_hwee_morgan_malik_harris_stern_2023, title={Pharmacokinetics of a single dose of Aficamten (CK-274) on cardiac contractility in a A31P MYBPC3 hypertrophic cardiomyopathy cat model}, volume={46}, url={https://europepmc.org/articles/PMC10099566}, DOI={10.1111/jvp.13103}, abstractNote={AbstractHypertrophic cardiomyopathy (HCM) is the most prevalent cardiac disease in cats and lacks efficacious preclinical pharmacologic intervention, prompting investigation of novel therapies. Genetic mutations encoding sarcomeric proteins are implicated in the development of HCM and small molecule myosin inhibitors are an emerging class of therapeutics designed to target the interaction of actin and myosin to alleviate the detrimental effects of inappropriate contractile protein interactions. The purpose of this study was to characterize the pharmacodynamic effects of a single oral dose of the novel cardiac myosin inhibitor aficamten (CK‐274) on cardiac function in purpose bred cats with naturally occurring A31P MYBPC3 mutation and a clinical diagnosis of HCM with left ventricular outflow tract obstruction (LVOTO). Five purpose bred cats were treated with aficamten (2 mg/kg) or vehicle and echocardiographic evaluations were performed at 0, 6, 24, and 48 h post‐dosing. High dose aficamten (2 mg/kg) reduced left ventricular fractional shortening (LVFS%) by increasing the LV systolic internal dimension (LVIDs) and reduced isovolumic relaxation time (IVRT) compared with baseline without significant adverse effects. The marked reduction in systolic function and reduced IVRT coupled with an increased heart rate in treated cats, suggest a lower dose may be optimal. Further studies to determine optimal dosing of aficamten are indicated.}, number={1}, journal={Journal of veterinary pharmacology and therapeutics}, author={Sharpe, Ashley N and Oldach, Maureen S and Kaplan, Joanna L and Rivas, Victor and Kovacs, Samantha L and Hwee, Darren T and Morgan, Bradley P and Malik, Fady I and Harris, Samantha P and Stern, Joshua A}, year={2023}, pages={52—61} }
 @article{tan_li_ueda_stern_hussain_haginoya_sharpe_gunther-harrington_epstein_nguyen_2022, title={Platelet Priming and Activation in Naturally Occurring Thermal Burn Injuries and Wildfire Smoke Exposure Is Associated With Intracardiac Thrombosis and Spontaneous Echocardiographic Contrast in Feline Survivors}, volume={9}, ISSN={2297-1769}, url={http://dx.doi.org/10.3389/fvets.2022.892377}, DOI={10.3389/fvets.2022.892377}, abstractNote={Wildfires pose a major health risk for humans, wildlife, and domestic animals. We previously discovered pathophysiologic parallels between domestic cats with naturally occurring smoke inhalation and thermal burn injuries and human beings with similar injuries; these were characterized by transient myocardial thickening, cardiac troponin I elevation and formation of intracardiac thrombosis. While the underlying mechanisms remain unclear, results from murine models suggest that platelet priming and activation may contribute to a global hypercoagulable state and thrombosis. Herein, we evaluated and compared the degree of platelet activation, platelet response to physiologic agonists and levels of platelet-derived microvesicles (PDMV) in 29 cats with naturally occurring wildfire thermal injuries (WF), 21 clinically healthy cats with subclinical hypertrophic cardiomyopathy (HCM) and 11 healthy cats without HCM (CC). We also quantified and compared circulating PDMVs in WF cats to CC cats. In addition, we examined the association between thrombotic events, severity of burn injuries, myocardial changes, and the degree of platelet activation in cats exposed to wildfires. Flow cytometric detection of platelet surface P-selectin expression showed that WF cats had increased platelet response to adenosine diphosphate (ADP) and thrombin compared to the two control groups indicating the presence of primed platelets in circulation. In addition, cats in the WF group had increased circulating levels of PDMV, characterized by increased phosphatidylserine on the external leaflet. Cats in the WF group with documented intracardiac thrombosis had elevated platelet activation and platelet priming in the presence of ADP. While high dose arachidonic acid (AA) mostly resulted in platelet inhibition, persistent response to AA was noted among cats in the WF group with intracardiac thrombosis. Univariate and multiple logistic regression analyses demonstrated that increased platelet response to AA was independently associated with thrombotic events. This is the first study reporting the significant association between platelet priming and intracardiac thrombosis in domestic cats with naturally occurring wildfire-related injuries and smoke inhalation. Further studies are required to delineate additional mechanisms between inflammation and thrombosis, especially regarding platelet primers and the cyclooxygenase pathway.One Sentence SummaryPlatelet activation and shedding of platelet-derived microvesicles due to platelet priming is present following naturally occurring wildfire smoke exposure and thermal burn injuries in a population of domestic cats.}, journal={Frontiers in Veterinary Science}, publisher={Frontiers Media SA}, author={Tan, Avalene W. K. and Li, Ronald H. L. and Ueda, Yu and Stern, Joshua A. and Hussain, Mehrab and Haginoya, Satoshi and Sharpe, Ashely N. and Gunther-Harrington, Catherine T. and Epstein, Steven E. and Nguyen, Nghi}, year={2022}, month={Jul} }
 @article{mayhew_balsa_stern_johnson_kaplan_gonzales_steffey_gibson_hagen_culp_et al._2022, title={Resolution, recurrence, and chyle redistribution after thoracic duct ligation with or without pericardiectomy in dogs with naturally occurring idiopathic chylothorax}, volume={261}, url={https://doi.org/10.2460/javma.22.08.0381}, DOI={10.2460/javma.22.08.0381}, abstractNote={To document outcomes of thoracoscopic treatment of idiopathic chylothorax (IC) in dogs with and without constrictive pericardial physiology (CPP) and evaluate patterns of chyle flow redistribution after thoracic duct ligation (TDL).26 client-owned dogs.In this prospective cohort study, echocardiography and cardiac catheterization were performed to document CPP in dogs with IC. Thoracoscopic TDL with pericardiectomy was performed if CPP was present (TDL/P group). Dogs without evidence of CPP underwent thoracoscopic TDL alone (TDL group). Dogs underwent preoperative, immediate postoperative, and 3-month postoperative CT lymphangiography studies when possible. Perioperative morbidity, resolution and late recurrence rates, and long-term outcome were recorded.17 dogs underwent TDL, and 9 underwent TDL/P. Twenty-five of 26 (96%) survived the perioperative period. One dog died from ventricular fibrillation during pericardiectomy. Resolution rates for TDL and TDL/P were 94% and 88%, respectively (P = .55), with 1 late recurrence occurring in the TDL group in a median follow-up of 25 months (range, 4 to 60 months). On 3-month postoperative CT lymphangiography studies, ongoing chyle flow past the ligation site was demonstrated in 5 of 17 dogs, of which 1 dog developed recurrence at 13 months postoperatively. In 15 of 17 dogs, chylous redistribution after TDL was principally by retrograde flow to the lumbar lymphatic plexus.In dogs without evidence of CPP, TDL alone was associated with a very good prognosis for treatment of IC. In the absence of CPP, the additional benefit of pericardiectomy in the treatment of IC is questionable.}, number={5}, journal={Journal of the American Veterinary Medical Association}, author={Mayhew, Philipp D and Balsa, Ingrid M and Stern, Joshua A and Johnson, Eric G and Kaplan, Joanna and Gonzales, Carina and Steffey, Michelle A and Gibson, Erin and Hagen, Briana and Culp, William T N and et al.}, year={2022}, pages={696—704} }
 @article{schober_fox_abbott_côté_luis-fuentes_matos_stern_visser_scollan_chetboul_et al._2022, title={Retrospective evaluation of hypertrophic cardiomyopathy in 68 dogs}, volume={36}, url={https://europepmc.org/articles/PMC9151492}, DOI={10.1111/jvim.16402}, abstractNote={Abstract Background There is a lack of clinical data on hypertrophic cardiomyopathy (HCM) in dogs. Hypothesis/Objectives To investigate signalment, clinical signs, diagnostic findings, and survival in dogs with HCM. Animals Sixty‐eight client‐owned dogs. Methods Retrospective multicenter study. Medical records were searched between 2003 and 2015. The diagnosis of left ventricular (LV) hypertrophy was made by echocardiographic examination. Results Three hundred and forty‐five dogs with LV hypertrophy were identified, of which 277 were excluded. The remaining 68 dogs were 0.3 to 14 years old and predominantly <10 kg (85%), and without a sex predilection. Twenty‐four % were Shih Tzu and 24% terrier breeds. Most (80%) had a systolic heart murmur. Owner‐determined exercise intolerance (37%) and syncope (18%) were most commonly reported signs. The majority (84%) of dogs had symmetrical LV hypertrophy, whereas asymmetrical septal and LV free wall hypertrophy was observed in 9% and 6% of dogs, respectively. Isolated basal interventricular septal hypertrophy was not observed. Commonly recorded were systolic anterior motion of the mitral valve (60%) and LV diastolic dysfunction (89% of dogs where diastolic function was evaluated). Six dogs died unexpectedly, and 3 developed congestive heart failure. Known survival times were between 1 day and 114 months after diagnosis. Conclusions and Clinical Importance Hypertrophic cardiomyopathy in dogs should be considered as a differential diagnosis if LV hypertrophy is identified. Small breed dogs are overrepresented, and it is uncommon for dogs with HCM to develop CHF although sudden death can occur.}, number={3}, journal={Journal of veterinary internal medicine}, author={Schober, Karsten E and Fox, Phillip R and Abbott, Jonathan and Côté, Etienne and Luis-Fuentes, Virginia and Matos, Jose Novo and Stern, Joshua A and Visser, Lance and Scollan, Katherine F and Chetboul, Valerie and et al.}, year={2022}, pages={865—876} }
 @article{schipper_ohlsson_longeri_hayward_mouttham_ferrari_smets_ljungvall_häggström_stern_et al._2022, title={The TNNT2:c.95-108G>A variant is common in Maine Coons and shows no association with hypertrophic cardiomyopathy}, volume={53}, url={https://biblio.ugent.be/publication/8754776/file/8754777.pdf}, DOI={10.1111/age.13223}, abstractNote={Hypertrophic cardiomyopathy (HCM) is a common and potentially fatal heart disease in many cat breeds. An intronic variant in TNNT2, c.95-108G>A, was recently reported as the cause of HCM in the Maine Coon. The aim of this study was to determine this variant's allele frequency in different populations and its possible association with HCM. Based on 160 Maine Coon samples collected in Belgium, Italy, Sweden and the USA, the variant's allele frequency was estimated to be 0.32. Analysis of the 99 Lives feline whole genome sequencing database showed that the TNNT2 variant also occurs in other breeds, as well as mixed-breed cats. Comparison of 31 affected and 58 healthy cats did not reveal significantly increased odds for HCM in homozygotes. Based on the combined evidence and in agreement with the standards and guidelines for the interpretation of sequence variants, this variant is currently classified as a variant of unknown significance and should not be used for breeding decisions regarding HCM.}, number={4}, journal={Animal genetics}, author={Schipper, Tom and Ohlsson, Åsa and Longeri, Maria and Hayward, Jessica J and Mouttham, Lara and Ferrari, Paolo and Smets, Pascale and Ljungvall, Ingrid and Häggström, Jens and Stern, Joshua A and et al.}, year={2022}, pages={526—529} }
 @article{ueda_li_nguyen_ontiveros_kovacs_oldach_vernau_court_stern_2021, title={A genetic polymorphism in P2RY(1) impacts response to clopidogrel in cats with hypertrophic cardiomyopathy}, volume={11}, ISSN={["2045-2322"]}, url={https://europepmc.org/articles/PMC8206363}, DOI={10.1038/s41598-021-91372-3}, abstractNote={AbstractClopidogrel is converted to its active metabolite by cytochrome P450 isoenzymes and irreversibly inhibits platelet activation by antagonizing the adenosine-diphosphate (ADP) receptor. It is frequently used in cats with hypertrophic cardiomyopathy (HCM) to prevent thromboembolic complications. However, significant interpatient variability of the response to clopidogrel therapy has been suspected. In this study, we assessed the impact of single nucleotide polymorphisms (SNPs) within ADP receptor (P2RY1, P2RY12) and cytochrome P450 isoenzyme (CYP2C41) genes on platelet inhibition by clopidogrel administration in cats with HCM. Forty-nine cats completed the study, and blood samples were obtained before and after clopidogrel therapy to assess the degree of platelet inhibition based on flow cytometry and whole blood platelet aggregometry. Plasma concentrations of clopidogrel metabolites were measured after the last dose of clopidogrel. Whole blood platelet aggregometry revealed a significant reduction of platelet inhibition by clopidogrel in cats with the P2RY1:A236G and the P2RY12:V34I variants. The association with the P2RY1:A236G variant and clopidogrel resistance remained significant after adjustment for multiple comparisons. This study demonstrated that a genetic polymorphism in the P2RY1 gene altered response to clopidogrel therapy and suggests that clinicians may consider alternative or additional thromboprophylactic therapy in cats with the P2RY1:A236G variant.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Ueda, Yu and Li, Ronald H. L. and Nguyen, Nghi and Ontiveros, Eric S. and Kovacs, Samantha L. and Oldach, Maureen S. and Vernau, Karen M. and Court, Michael H. and Stern, Joshua A.}, year={2021}, month={Jun} }
 @article{oldach_ueda_ontiveros_fousse_visser_stern_2021, title={Acute pharmacodynamic effects of pimobendan in client-owned cats with subclinical hypertrophic cardiomyopathy}, volume={17}, ISSN={["1746-6148"]}, url={https://europepmc.org/articles/PMC7903657}, DOI={10.1186/s12917-021-02799-9}, abstractNote={Abstract
                Background
                Prior studies have suggested that pimobendan is associated with several positive effects in cats, including improved survival in cats with congestive heart failure and improved left atrial function in research colony cats with hypertrophic cardiomyopathy (HCM) and normal cats. However, there is still a paucity of pharmacodynamic data refuting or supporting the use of pimobendan in a clinical cat population. This clinical trial aimed to evaluate the pharmacodynamic effects and tolerability of a single dose of pimobendan in cats with HCM. Echocardiograms and Doppler-derived systolic blood pressures were performed in 21 client-owned cats with subclinical HCM at baseline and 90-min after oral administration of 1.25 mg of pimobendan (Vetmedin). Seven additional cats were evaluated post-placebo administration to account for intra-day variability.
              
                Results
                Heart rate, systolic blood pressure, and murmur grade were not significantly different between baseline and post-pimobendan evaluations. Left auricular blood flow velocity, left atrial size, and left ventricular fractional shortening were not significantly different between baseline and post-pimobendan evaluations.
                Mean (± standard deviation) tissue Doppler peak systolic velocity of the mitral annulus was significantly higher following pimobendan (7.4 cm/s ± 1.5 vs 8.5 ± 1.6; p = 0.02). Median (min, max) left-ventricular outflow tract maximum velocity was significantly higher following pimobendan [1.9 m/sec (1.5, 3.4) vs 2.6 m/sec (2.0, 4.0); p = 0.01]. Mean right-ventricular outflow tract maximum velocity was also significantly higher following pimobendan (1.5 m/s ± 0.51 vs 2.0 ± 0.53; p = 0.004). Mean left atrial fractional shortening was significantly higher following pimobendan (28% ± 6 vs 32% ± 7; p = 0.02).
                No adverse events were observed following pimobendan administration.
                Right ventricular outflow tract velocity was significantly higher following placebo in control cats (1.02 ± 0.21 versus 1.31 ± 0.31; p = 0.01). No other significant differences were detected.
              
                Conclusions
                In client-owned cats with HCM, pimobendan acutely increased left atrial function and mildly increased left ventricular systolic function. Left ventricular outflow tract velocity was increased after pimobendan. Pimobendan was well tolerated in the acute setting in cats with HCM. The findings of this prospective, acute-dosing study confirm previous findings in research animals and retrospective analyses and suggest that chronic dosing studies are safe and warranted.
              }, number={1}, journal={BMC VETERINARY RESEARCH}, author={Oldach, Maureen S. and Ueda, Yu and Ontiveros, Eric S. and Fousse, Samantha L. and Visser, Lance C. and Stern, Joshua A.}, year={2021}, month={Feb} }
 @article{hsue_sharpe_darling_visser_choi_stern_2021, title={Aorto-left atrial fistula secondary to infective aortic endocarditis and endarteritis in a cat with valvular aortic stenosis}, volume={35}, url={https://doi.org/10.1016/j.jvc.2021.03.007}, DOI={10.1016/j.jvc.2021.03.007}, journal={Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology}, author={Hsue, W and Sharpe, AN and Darling, SL and Visser, LC and Choi, E and Stern, JA}, year={2021}, pages={101—107} }
 @article{raleigh_culp_brady_al-nadaf_kent_kaplan_stern_visser_niedringhaus_wolf_et al._2021, title={Biopsy of an intracardiac paraganglioma in a dog using a fluoroscopically guided endovascular technique}, volume={35}, url={https://europepmc.org/articles/PMC8162608}, DOI={10.1111/jvim.16118}, abstractNote={A 10-year-old female spayed mixed breed dog was evaluated for diarrhea and vomiting. Diagnostic imaging demonstrated the presence of an intracardiac mass. A modified Seldinger technique was used to access the right jugular vein, and an endomyocardial biopsy forceps was introduced through a sheath to obtain several biopsies. Histopathology and immunohistochemistry demonstrated a paraganglioma. The dog underwent 1 fraction of radiotherapy and l-asparaginase chemotherapy and was discharged. The dog developed a pulmonary thromboembolism 2 days after radiotherapy and chemotherapy, and the owner elected humane euthanasia. Although long-term assessment of treatment response was unable to be performed, this novel diagnostic option could be considered for similar cases due to success in obtaining a histopathologic diagnosis, which is essential in developing a disease-specific treatment plan. This report also describes the use of radiotherapy for primary treatment of an intracardiac neoplasm, which can be a consideration in the future.}, number={3}, journal={Journal of veterinary internal medicine}, author={Raleigh, Joseph S and Culp, William T N and Brady, Rachel and Al-Nadaf, Sami and Kent, Michael S and Kaplan, Joanna L and Stern, Joshua A and Visser, Lance C and Niedringhaus, Kevin D and Wolf, Tatiana G and et al.}, year={2021}, pages={1536—1541} }
 @article{adin_stern_2021, title={Canine cardiomyopathies.}, url={https://doi.org/10.1016/j.jvc.2021.12.008}, DOI={10.1016/j.jvc.2021.12.008}, journal={Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology}, author={Adin, D and Stern, J}, year={2021}, month={Dec} }
 @article{grigg_ueda_walker_hart_simas_stern_2021, title={Comparative Assessment of Heart Rate Variability Obtained via Ambulatory ECG and Polar Heart Rate Monitors in Healthy Cats: A Pilot Study}, volume={8}, ISSN={["2297-1769"]}, url={https://europepmc.org/articles/PMC8606523}, DOI={10.3389/fvets.2021.741583}, abstractNote={Chronic exposure to stressful environments can negatively impact cats' health and welfare, affecting behavioral, autonomic, endocrine, and immune function, as with cats in shelters. Low-stress handling practices likely improve shelter cat welfare, but data supporting improved outcomes remain limited. Cardiac activity, particularly heart rate variability (HRV), is an indicator of stress and emotional state in humans and non-human animals, tracking important body functions associated with stress responsiveness, environmental adaptability, mental, and physical health. HRV studies in cats are limited, involving mainly anesthetized or restrained cats. This pilot study tested the feasibility of obtaining HRV data from unrestrained cats, using a commercially available cardiac monitoring system (Polar H10 with chest strap), compared with data from a traditional ambulatory electrocardiogram. Simultaneous data for the two systems were obtained for five adult cats. Overall, the Polar H10 monitor assessments of HRV were lower than the true HRV assessment by ambulatory ECG, except for SDNN. Correlation between the two systems was weak. Possible reasons for the lack of agreement between the two methods are discussed. At this time, our results do not support the use of Polar H10 heart rate monitors for studies of HRV in cats.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Grigg, Emma K. and Ueda, Yu and Walker, Ashley L. and Hart, Lynette A. and Simas, Samany and Stern, Joshua A.}, year={2021}, month={Nov} }
 @article{lo_walker_georges_li_stern_2021, title={Dual therapy with clopidogrel and rivaroxaban in cats with thromboembolic disease}, volume={24}, ISSN={1098-612X 1532-2750}, url={http://dx.doi.org/10.1177/1098612x211013736}, DOI={10.1177/1098612x211013736}, abstractNote={Objectives Feline arterial thromboembolism (ATE), an often devastating outcome, was recently shown to affect 11.3% of cats with hypertrophic cardiomyopathy over 10 years. Current American College of Veterinary Internal Medicine guidelines recommend the use of clopidogrel in cats at risk for ATE, with addition of a factor Xa inhibitor in very high risk or post-ATE cases. To date, no studies have examined the safety or efficacy of this combined antithrombotic therapy. This retrospective case series aimed to assess the frequency and type of adverse events that occurred in cats prescribed dual clopidogrel and rivaroxaban therapy. Secondary aims were to evaluate indications for dual therapy and clinical outcome. Methods The study included 32 cats prescribed clopidogrel (18.75 mg PO q24h) and rivaroxaban (2.5 mg PO q24h) on an outpatient basis over a 5-year period. Results Cats were prescribed dual therapy for at least one of the following: ATE event (n = 18), presence of an intracardiac thrombi (n = 17) or presence of spontaneous echocardiographic contrast (SEC) (n = 16). Five cats experienced adverse effects that could be attributed to medications, a median of 13 days from initiation (epistaxis, hematemesis, hematochezia or hematuria). No cat required hospitalization as a result of these events. Median survival time from onset of therapy was 257 days (interquartile range [IQR] = 38–497) for all cats, 502 days (IQR = 171–663) for ATE cats, 725 days (IQR = 133–856) for cats with an ATE to two or more limbs and 301 days (IQR = 221–431) for cats with only one limb affected. Recurrence rate of ATE while on dual therapy was 16.7%; no cat newly developed an ATE while on dual therapy. Conclusions and relevance Dual antithrombotic therapy with clopidogrel and rivaroxaban resulted in a low reported incidence of adverse events. Cats placed on dual therapy for an ATE event experienced a low rate of recurrence and effective thromboprophylaxis was achieved in cats with intracardiac thrombi or SEC. }, number={4}, journal={Journal of Feline Medicine and Surgery}, publisher={SAGE Publications}, author={Lo, Sara T and Walker, Ashley L and Georges, Catherine J and Li, Ronald HL and Stern, Joshua A}, year={2021}, month={May}, pages={277–283} }
 @article{ontiveros_stern_2021, title={Genetics of canine subvalvular aortic stenosis (SAS)}, volume={8}, url={https://europepmc.org/articles/PMC8103588}, DOI={10.1186/s40575-021-00103-4}, abstractNote={Abstract Subvalvular aortic stenosis (SAS) is one of the most common congenital heart defects of dogs. The disease is characterized by obstruction of the left ventricular outflow tract, resulting in pressure overload on the left ventricle. The etiology of obstruction is a fibromuscular nodule, ridge, or ring of tissue that increases aortic outflow tract velocity. This review is focused on the prevalence, inheritance pattern, and current genetic insights of canine SAS. The prevalence of this disease was reported at 4.7 % in a large veterinary referral hospital. The mode of inheritance for this disease has also been described in breeds with a high disease prevalence such as the Bullmastiff, Bouvier des Flandres, Dogue de Bordeaux, Golden Retriever, Newfoundland, and Rottweiler. Genetic investigations seeking to identify causative mutations for SAS are lacking with only a single published variant associated with SAS in Newfoundlands.}, number={1}, journal={Canine medicine and genetics}, author={Ontiveros, Eric S and Stern, Joshua A}, year={2021}, pages={4} }
 @article{ueda_kovacs_reader_roberts_stern_2021, title={Heritability and Pedigree Analyses of Hypertrophic Cardiomyopathy in Rhesus Macaques (Macaca Mulatta)}, volume={8}, ISSN={["2297-1769"]}, url={https://europepmc.org/articles/PMC8206789}, DOI={10.3389/fvets.2021.540493}, abstractNote={In a colony of rhesus macaques at California National Primate Research Center (CNPRC), naturally occurring hypertrophic cardiomyopathy (HCM) classified by left ventricular hypertrophy without obvious underlying diseases has been identified during necropsy over the last two decades. A preliminary pedigree analysis suggested a strong genetic predisposition of this disease with a founder effect. However, the mode of inheritance was undetermined due to insufficient pedigree data. Since 2015, antemortem examination using echocardiographic examination as well as other cardiovascular analyses have been performed on large numbers of rhesus macaques at the colony. Based on antemortem examination, HCM was diagnosed in additional 65 rhesus macaques. Using HCM cases diagnosed based on antemortem and postmortem examinations, the heritability (h2) was estimated to determine the degree of genetic and environmental contributions to the development of HCM in rhesus macaques at the CNPRC. The calculated mean and median heritability (h2) of HCM in this colony of rhesus macaques were 0.5 and 0.51 (95% confidence interval; 0.14–0.82), respectively. This suggests genetics influence development of HCM in the colony of rhesus macaques. However, post-translational modifications and environmental factors are also likely to contribute the variability of phenotypic expression. Based on the pedigree analysis, an autosomal recessive trait was suspected, but an autosomal dominant mode of inheritance with incomplete penetrance was also possible. Further investigation with more data from siblings, offspring, and parents of HCM-affected rhesus macaques are warranted. Importantly, the findings of the present study support conducting genetic investigations such as whole genome sequencing to identify the causative variants of inherited HCM in rhesus macaques.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Ueda, Yu and Kovacs, Samantha and Reader, Rachel and Roberts, Jeffrey A. and Stern, Joshua A.}, year={2021}, month={Jun} }
 @article{lyons_buckley_harvey_2021, title={Mining the 99 Lives Cat Genome Sequencing Consortium database implicates genes and variants for the Ticked locus in domestic cats (Felis catus)}, volume={52}, url={https://europepmc.org/articles/PMC8252059}, DOI={10.1111/age.13059}, abstractNote={SummaryTabby patterns of fur coats are defining characteristics in wild and domestic felids. Historically, three autosomal alleles at one locus (Tabby): Abyssinian (Ta; a.k.a. ticked), mackerel (Tm; a.k.a. striped) and blotched (tb; a.k.a. classic, blotched) were thought to control these patterns in domestic cats and their breeds. Currently, at least three loci influence cat tabby markings, two of which are designated Tabby and Ticked. The Tabby locus is laeverin (LVRN) and affects the mackerel and blotched patterns. The unidentified gene for the Ticked locus on cat chromosome B1 was suggested to control the presence or absence of the ticked pattern (Tabby – Abyssinian (Ta; a.k.a. ticked). The cat reference genome (Cinnamon, the Abyssinian) has the ticked phenotype and the variant dataset and coat phenotypes from the 99 Lives Cat Genome Consortium (195 cats) were used to identify candidate genes and variants associated with the Ticked locus. Two strategies were used to find the Ticked allele(s), one considered Cinnamon with the reference allele or heterozygous (Strategy A) and the other considered Cinnamon as having the variant allele or heterozygous (Strategy B). For Strategy A, two variants in Dickkopf Wnt Signaling Pathway Inhibitor 4 (DKK4), a p.Cys63Tyr (B1:41621481, c.188G>A) and a less common p.Ala18Val (B1:42620835, c.53C>T) variant are suggested as two alleles influencing the Ticked phenotype. Bioinformatic and molecular modeling analysis suggests that these changes disrupt a key disulfide bond in the Dkk4 cysteine‐rich domain 1 or Dkk4 signal peptide cleavage respectively. All coding variants were excluded as Ticked alleles using Strategy B.}, number={3}, journal={Animal genetics}, author={Lyons, LA and Buckley, RM and Harvey, RJ}, year={2021}, pages={321—332} }
 @article{genova_nonnis_maffioli_tedeschi_strillacci_carisetti_sironi_cupaioli_di nanni_mezzelani_et al._2021, title={Multi-omic analyses in Abyssinian cats with primary renal amyloid deposits}, volume={11}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/s41598-021-87168-0}, DOI={10.1038/s41598-021-87168-0}, abstractNote={AbstractThe amyloidoses constitute a group of diseases occurring in humans and animals that are characterized by abnormal deposits of aggregated proteins in organs, affecting their structure and function. In the Abyssinian cat breed, a familial form of renal amyloidosis has been described. In this study, multi-omics analyses were applied and integrated to explore some aspects of the unknown pathogenetic processes in cats. Whole-genome sequences of two affected Abyssinians and 195 controls of other breeds (part of the 99 Lives initiative) were screened to prioritize potential disease-associated variants. Proteome and miRNAome from formalin-fixed paraffin-embedded kidney specimens of fully necropsied Abyssinian cats, three affected and three non-amyloidosis-affected were characterized. While the trigger of the disorder remains unclear, overall, (i) 35,960 genomic variants were detected; (ii) 215 and 56 proteins were identified as exclusive or overexpressed in the affected and control kidneys, respectively; (iii) 60 miRNAs were differentially expressed, 20 of which are newly described. With omics data integration, the general conclusions are: (i) the familial amyloid renal form in Abyssinians is not a simple monogenic trait; (ii) amyloid deposition is not triggered by mutated amyloidogenic proteins but is a mix of proteins codified by wild-type genes; (iii) the form is biochemically classifiable as AA amyloidosis.}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Genova, Francesca and Nonnis, Simona and Maffioli, Elisa and Tedeschi, Gabriella and Strillacci, Maria Giuseppina and Carisetti, Michela and Sironi, Giuseppe and Cupaioli, Francesca Anna and Di Nanni, Noemi and Mezzelani, Alessandra and et al.}, year={2021}, month={Apr} }
 @article{li_nguyen_stern_duler_2021, title={Neutrophil extracellular traps in feline cardiogenic arterial thrombi: a pilot study}, volume={24}, ISSN={1098-612X 1532-2750}, url={http://dx.doi.org/10.1177/1098612x211044986}, DOI={10.1177/1098612x211044986}, abstractNote={Objectives The aim of this study was to investigate the spatial distribution of neutrophil extracellular traps (NETs) in cardiogenic arterial thromboembolism (CATE). Specifically, we aimed to examine the related structural features of NETs in feline arterial thrombi in relation to their arterial locations. Methods Paraffin-embedded aortic bifurcations from nine cats with hypertrophic cardiomyopathy (four with CATE and five without) were deparaffinized, and NETs were identified by immunodetection based on colocalization of cell-free DNA, citrullinated histone H3 and neutrophil elastase. The distribution of NETs in thrombi within the aortic bifurcations and common iliac arteries (CIAs) was compared based on their proximity to the descending aorta (proximal, mid, distal). Ten random fields per section were captured at × 10 and × 20 magnification for each section of the clot and analyzed. Results The distributions of NETs in thrombi within the aortic bifurcation and CIAs were found to differ in relation to their assigned zones (proximal, mid, distal; P = 0.04); NETs were concentrated mostly in the proximal region in the aortic bifurcations (47.56%, interquartile range [IQR] 14.07–77.95) and CIAs (44.69%, IQR 24.65–85.28), compared with the distal regions (2.69%, IQR 0.10–50.04 [P = 0.027]; 7.08%, IQR 1.27–59.33 [P = 0.02]). Conclusions and relevance The variation in NET distribution within arterial thrombi may shed light on the pathogenesis of thrombus growth. This may be due to possible neutrophil entrapment or variations in shear stress. }, number={6}, journal={Journal of Feline Medicine and Surgery}, publisher={SAGE Publications}, author={Li, Ronald HL and Nguyen, Nghi and Stern, Joshua A and Duler, Laetitia M}, year={2021}, month={Sep}, pages={580–586} }
 @article{adin_atkins_friedenberg_stern_meurs_2021, title={Prevalence of an angiotensin-converting enzyme gene variant in dogs}, volume={8}, url={https://europepmc.org/articles/PMC8276509}, DOI={10.1186/s40575-021-00105-2}, abstractNote={Abstract Background Genetic heterogeneity of the canine angiotensin converting enzyme (ACE) gene is functionally important because the degree of aldosterone breakthrough with ACE-inhibitor therapy is greater in variant positive dogs compared to variant negative dogs, but the prevalence of the variant is not known. The purpose of this study was to determine ACE gene variant-positive prevalence in a population of 497 dogs of different breeds. Results Overall variant-positive prevalence was 31%, with 20% of dogs heterozygous and 11% of dogs homozygous. The variant was overrepresented in Irish Wolfhounds (prevalence 95%; P < .001), Dachshunds (prevalence 90%; P < .001), Cavalier King Charles Spaniels (prevalence 85%; P < .001), Great Danes (prevalence 84%; P < .001), and Bull Mastiffs (prevalence 58%; P = .02). Irish Wolfhounds were more likely to be homozygous than heterozygous ( P < .001). Conclusions Nearly one-third of dogs in this study were positive for a functionally important ACE gene variant, with wide prevalence variability between breeds. The clinical importance of high ACE gene variant-positive prevalence in some breeds requires further study because the highest prevalences were found in breeds that are predisposed to heart disease and therefore may be treated with ACE-inhibitors.}, number={1}, journal={Canine medicine and genetics}, author={Adin, DB and Atkins, CE and Friedenberg, SG and Stern, JA and Meurs, KM}, year={2021}, pages={6} }
 @article{fuentes_abbott_chetboul_côté_fox_häggström_kittleson_schober_stern_2020, title={ACVIM consensus statement guidelines for the classification, diagnosis, and management of cardiomyopathies in cats}, volume={34}, url={https://doi.org/10.1111/jvim.15745}, DOI={10.1111/jvim.15745}, abstractNote={Abstract Cardiomyopathies are a heterogeneous group of myocardial disorders of mostly unknown etiology, and they occur commonly in cats. In some cats, they are well‐tolerated and are associated with normal life expectancy, but in other cats they can result in congestive heart failure, arterial thromboembolism or sudden death. Cardiomyopathy classification in cats can be challenging, and in this consensus statement we outline a classification system based on cardiac structure and function (phenotype). We also introduce a staging system for cardiomyopathy that includes subdivision of cats with subclinical cardiomyopathy into those at low risk of life‐threatening complications and those at higher risk. Based on the available literature, we offer recommendations for the approach to diagnosis and staging of cardiomyopathies, as well as for management at each stage.}, number={3}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Fuentes, Virginia Luis and Abbott, Jonathan and Chetboul, Valérie and Côté, Etienne and Fox, Philip R. and Häggström, Jens and Kittleson, Mark D. and Schober, Karsten and Stern, Joshua A.}, year={2020}, month={May}, pages={1062–1077} }
 @article{meurs_stern_adin_keene_de francesco_tou_2020, title={Assessment of <i>PDK4</i> and <i>TTN</i> gene variants in 48 Doberman Pinschers with dilated cardiomyopathy}, volume={257}, url={https://doi.org/10.2460/javma.2020.257.10.1041}, DOI={10.2460/javma.2020.257.10.1041}, abstractNote={To evaluate the frequency of variants in the pyruvate kinase dehydrogenase 4 (PDK4) and titin (TTN) genes in a group of Doberman Pinschers with dilated cardiomyopathy (DCM) and to determine whether there were unique clinical attributes to each variant.48 Doberman Pinschers with DCM.Doberman Pinschers with recently diagnosed DCM were identified, and genomic DNA from each was genotyped with a PCR assay for detection of PDK4 and TTN genetic variants. Dogs were grouped on the basis of whether they had the TTN variant alone, PDK4 variant alone, both variants, or neither variant. Descriptive statistics were compiled for dog age, body weight, and left ventricular dimensions and fractional shortening and for the presence of ventricular and supraventricular arrhythmias and heart failure. Results were compared across groups.Of the 48 dogs, 28 had the TTN variant alone, 10 had both variants, 6 had neither variant, and 4 had the PDK4 variant alone. The mean age was younger for dogs with the PDK4 variant alone, compared with other dogs. However, the number of dogs with the PDK4 variant alone was very small, and there was an overlap in age across groups. No other meaningful differences were detected across groups, and independent genotype-phenotype relationships were not identified.Although findings indicated that the TTN variant was most common, 6 dogs had neither variant, and this fact supported the concept of ≥ 1 other genetic contributor to DCM in Doberman Pinschers. Future studies are warranted to evaluate genotype-phenotype relationships in Doberman Pinschers with DCM.}, number={10}, journal={Journal of the American Veterinary Medical Association}, author={Meurs, Kathryn M and Stern, Joshua A and Adin, Darcy and Keene, Bruce W and De Francesco, Theresa C and Tou, Sandra P}, year={2020}, pages={1041—1044} }
 @article{sharpe_gunther-harrington_epstein_li_stern_2020, title={Cats with thermal burn injuries from California wildfires show echocardiographic evidence of myocardial thickening and intracardiac thrombi}, volume={10}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/s41598-020-59497-z}, DOI={10.1038/s41598-020-59497-z}, abstractNote={AbstractRecent increases in the prevalence and severity of wildfires in some regions have resulted in an increased frequency of veterinary burn patients. Few studies exist regarding diagnostics and management of burn wounds in veterinary patients and current knowledge is extrapolated from human literature and research models. Post-burn cardiac injury is a common finding and predictor of mortality in human patients and echocardiography is an important tool in monitoring response to therapy and predicting outcome. We describe the notable findings from cats naturally exposed to California wildfires in 2017 and 2018. Domestic cats (n = 51) sustaining burn injuries from the Tubbs (2017) and Camp (2018) wildfires were prospectively enrolled and serial echocardiograms and cardiac troponin I evaluations were performed. Echocardiograms of affected cats revealed a high prevalence of myocardial thickening (18/51) and spontaneous echocardiographic contrast and thrombi formation (16/51). Forty-two cats survived to discharge and 6 died or were euthanized due to a possible cardiac cause. For the first time, we describe cardiovascular and coagulation effects of thermal burn and smoke inhalation in cats. Further studies in veterinary burn victims are warranted and serve as a translational research opportunity for uncovering novel disease mechanisms and therapies.}, number={1}, journal={Scientific Reports}, publisher={Springer Science and Business Media LLC}, author={Sharpe, Ashley N. and Gunther-Harrington, Catherine T. and Epstein, Steven E. and Li, Ronald H. L. and Stern, Joshua A.}, year={2020}, month={Feb}, pages={2648} }
 @article{fujita_kent_wisner_johnson_stern_qi_boone_yamamoto_2020, title={Combined Assessment of Pulmonary Ventilation and Perfusion with Single-Energy Computed Tomography and Image Processing.}, url={https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726003}, DOI={10.1016/j.acra.2020.04.004}, journal={Academic radiology}, author={Fujita, Y and Kent, M and Wisner, E and Johnson, L and Stern, J and Qi, L and Boone, J and Yamamoto, Tokihiro}, year={2020}, month={Jun} }
 @article{ontiveros_whelchel_yu_kaplan_sharpe_fousse_crofton_fascetti_stern_2020, title={Development of plasma and whole blood taurine reference ranges and identification of dietary features associated with taurine deficiency and dilated cardiomyopathy in golden retrievers: A prospective, observational study}, volume={15}, url={https://doi.org/10.1371/journal.pone.0233206}, DOI={10.1371/journal.pone.0233206}, abstractNote={Introduction A surge in Food and Drug Administration (FDA) consumer complaints identified concerns that legume-rich, grain-free diets were associated with nutritionally-mediated dilated cardiomyopathy (DCM). Golden retrievers represent the most reported breed affected by this condition and previous studies documented the disease is responsive to dietary change and taurine supplementation. Although dietary findings across cases are compelling, prospective studies with control groups are lacking. The role of diet in developing taurine deficiency and echocardiographic changes consistent with DCM in healthy dogs is unknown. Objectives We hypothesized that golden retrievers eating non-traditional diets are at a higher risk of having taurine deficiency and nutritionally-mediated DCM compared with those eating traditional commercial diets. We aimed to compare taurine concentrations and echocardiographic indices of systolic function between golden retrievers in each diet group and elucidate associations between diet and these variables. Additionally, we aimed to generate breed-specific reference intervals for whole blood and plasma taurine concentrations. Animals 86 golden retrievers. Methods Golden retrievers eating traditional or non-traditional diets were evaluated and diet history, taurine concentrations and echocardiographic data were collected. Dietary features, taurine concentrations and echocardiographic findings were compared between diet groups. Relative risks were calculated for the likelihood of echocardiographic abnormalities and taurine deficiency in each diet group. Breed-specific reference intervals were constructed for taurine concentrations in dogs from the traditional diet group. Results Golden retrievers eating non-traditional diets had significantly lower taurine concentrations and more frequent systolic dysfunction. Breed specific reference intervals are higher than previously reported across breeds. Conclusions Non-traditional diets, which were typically grain-free and contained legumes in this study, were significantly associated with and have increased relative risk for the identification of taurine deficiency and echocardiographic abnormalities consistent with nutritionally-mediated DCM. These findings were identifiable in the absence of clinical signs and support the findings of multiple previous studies and the ongoing FDA investigation.}, number={5}, journal={PLOS ONE}, author={Ontiveros, Eric S. and Whelchel, Bradley D. and Yu, Joshua and Kaplan, Joanna L. and Sharpe, Ashley N. and Fousse, Samantha L. and Crofton, Amanda E. and Fascetti, Andrea J. and Stern, Joshua A.}, editor={Staffieri, FrancescoEditor}, year={2020}, month={May}, pages={e0233206} }
 @article{ueda_duler_elliot_sosa_roberts_stern_2020, title={Echocardiographic reference intervals with allometric scaling of 823 clinically healthy rhesus macaques (Macaca mulatta)}, volume={16}, ISSN={["1746-6148"]}, url={https://europepmc.org/articles/PMC7510309}, DOI={10.1186/s12917-020-02578-y}, abstractNote={Abstract
                Background
                Echocardiography is commonly used for assessing cardiac structure and function in various species including non-human primates. A few previous studies reported normal echocardiographic reference intervals of clinically healthy rhesus macaques under sedation. However, these studies were under-powered, and the techniques were not standardized. In addition, body weight, age, and sex matched reference intervals should be established as echocardiographic measurements are commonly influenced by these variables. The purpose of this study was to establish reference intervals for complete echocardiographic parameters based on a large cohort of clinically healthy rhesus macaques with wide ranges of weight and age distributions using allometric scaling.
              
                Results
                A total of 823 rhesus macaques (ages 6 months to 31 years old; body weights 1.4 to 22.6 kg) were enrolled. Of these rhesus macaques, 421 were males and 402 were females. They were assessed with a complete echocardiographic examination including structural and functional evaluation under sedation with ketamine hydrochloride. The reference intervals of the key echocardiographic parameters were indexed to weight, age, and sex by calculating the coefficients of the allometric eq. Y = aMb. On correlation matrix, body weight, age, sex, and heart rate were significantly correlated with various echocardiographic parameters and some of the parameters were strongly correlated with body weight and age. Multiple regression analysis revealed that heart rate and body weight statistically significantly predicted several echocardiographic parameters. Valve regurgitation including tricuspid, aortic, pulmonic, and mitral regurgitations without other cardiac structural and functional abnormalities are common in clinically healthy rhesus macaques under ketamine sedation.
              
                Conclusions
                In this study, the reference intervals of echocardiographic parameters were established by performing complete echocardiographic examinations on a large number of clinical healthy rhesus macaques. In addition, allometric scaling was performed based on their weight, and further indexed to age and sex. These allometrically scaled reference intervals can be used to accurately evaluate echocardiographic data in rhesus macaques and diagnose structural and functional evidence of cardiac disease.
              }, number={1}, journal={BMC VETERINARY RESEARCH}, author={Ueda, Yu and Duler, Laetitia M. M. and Elliot, Kami J. and Sosa, Paul-Michael D. and Roberts, Jeffrey A. and Stern, Joshua A.}, year={2020}, month={Sep} }
 @article{ueda_yee_williams_roberts_christe_stern_2020, title={Identifying Cardiac Diseases using Cardiac Biomarkers in Rhesus Macaques (<i>Macaca mulatta</i>)}, volume={70}, url={https://europepmc.org/articles/PMC7574220}, DOI={10.30802/aalas-cm-19-000117}, abstractNote={Cardiac biomarkers are an important tool for diagnosing cardiac diseases in both human and veterinary patients. Serum concentrations of N-terminal probrain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) have been used to indicate the presence of various cardiac diseases including hypertrophic cardiomyopathy (HCM) in various species including humans. However, these cardiac biomarkers have not been established as a diagnostic tool for detecting cardiac disease in rhesus macaques. In the rhesus macaque colony at the California National Primate Research Center, naturally occurring HCM and various other cardiac diseases have been identified. In this study, commercially available assays were used to measure serum cTnI and NT-proBNP concentrations to evaluate their utility as a diagnostic screening tool for cardiac diseases in rhesus macaques. This study revealed that the serum cTnI concentration was significantly higher in animals with echocardiographically apparent cardiac disease as compared with the animals that had no cardiac structural and functional changes (the control group). However, no significant differences were detected between animals with HCM and non-HCM cardiac disease. Because the area under the receiver operating characteristic curve was 0.81 when the serum cTnI was compared between the control and cardiac disease groups, serum cTnI was considered a moderately accurate test to predict the presence of cardiac disease. The optimal cut-off value of serum cTnI concentration for diagnosis of cardiac disease was 0.0085 ng/mL, with a sensitivity of 0.68 and specificity of 0.94. Significant but weak correlations were noted between the serum cTnI concentration and several echocardiographic parameters. Conversely, no significant differences in NT-proBNP concentrations were detected between animals with and without cardiac diseases. In conclusion, measurement of serum cTnI can be used to aid in diagnosing cardiac diseases in rhesus macaques. However, cTnI measurement does not replace echocardiographic evaluation to diagnose cardiac diseases in rhesus macaques due to the poor sensitivity of the assay and the weak correlation to with more established echocardiographic markers for cardiac disease.}, number={5}, journal={Comparative medicine}, author={Ueda, Yu and Yee, JoAnn L and Williams, Amber and Roberts, Jeffrey A and Christe, Kari L and Stern, Joshua A}, year={2020}, pages={348—357} }
 @article{willcox_belanger_burton_yu_ueda_visser_skorupski_stern_2020, title={Intramuscular Diphenhydramine Does Not Affect Acute Doxorubicin Infusion-Related Arrhythmia Number or Severity in a Prospective Crossover Study in Canine Lymphoma: A Pilot Study}, volume={7}, ISSN={["2297-1769"]}, url={https://europepmc.org/articles/PMC7379900}, DOI={10.3389/fvets.2020.00368}, abstractNote={Background: Doxorubicin (DOX) is one of the most effective chemotherapeutics for canine high-grade lymphoma. In addition to dose-dependent chronic cardiotoxicity, DOX can trigger acute cardiac arrhythmias during drug infusion. Diphenhydramine premedication is commonly used, as histamine release is a proposed mechanism for DOX-associated arrhythmogenesis. Hypothesis/Objectives: The study objectives were to evaluate the incidence and severity of DOX infusion-related cardiac arrhythmias in dogs with high-grade lymphoma and evaluate the effect of diphenhydramine premedication on arrhythmia frequency and severity during and after DOX infusion. Animals: Twenty-two client-owned dogs with cytologically/histopathologically confirmed high-grade lymphoma were recruited, of which 19 were enrolled and 9 completed the study. Methods: Dogs were screened by echocardiogram and concurrent electrocardiogram for this randomized prospective crossover study. Group A received no premedication for DOX #1 and was premedicated with diphenhydramine for DOX #2; Group B received diphenhydramine with DOX #1 and no premedication for DOX #2. For both visits, Holter monitor data were collected for 1 h pre-DOX and 3 h post-DOX administration. Results: Nineteen dogs were enrolled and 9 dogs [Group A (5), Group B (4)] completed the protocol. There was no statistical difference between the DOX alone and DOX + diphenhydramine when evaluating the total number of ventricular premature complexes (VPCs, P = 0.34), change in VPCs/hour (P = 0.25), total number of atrial premature complexes (APCs, P = 0.5), change in APCs/hour (P = 0.06), or ventricular arrhythmia severity score (P > 0.99). Conclusions and clinical importance: This study demonstrates that in these dogs with rigorous pretreatment cardiovascular screening, DOX infusion did not induce significant arrhythmias. Furthermore, these data suggest that, with this screening approach, diphenhydramine may not alter the arrhythmia number or severity in canine DOX recipients.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Willcox, Jennifer Lindley and Belanger, Catherine and Burton, Jenna Hart and Yu, Lydia and Ueda, Yu and Visser, Lance C. and Skorupski, Katherine and Stern, Joshua A.}, year={2020}, month={Jul} }
 @article{hagley_epstein_stern_poppenga_2020, title={Lamotrigine Toxicosis Treated with Intravenous Lipid Emulsion Therapy in a Dog}, volume={56}, url={https://doi.org/10.5326/JAAHA-MS-6815}, DOI={10.5326/jaaha-ms-6815}, abstractNote={A female spayed dachshund/mixed-breed dog was evaluated following ingestion of lamotrigine tablets with subsequent rapid onset of vomiting, diarrhea, and generalized tremoring. On initial examination, the dog was moderately obtunded and nonambulatory with intermittent myoclonus and hyperesthesia. Electrocardiogram revealed sinus tachycardia with prolongation of the QT interval. Intravenous lipid emulsion (ILE) infusion was initiated, with reduction in tremoring and improved patient mentation being noted after ∼20 min of therapy. An elevated cardiac troponin I value measured at 1.02 ng/mL the day after presentation. Serum toxicological assay revealed marked reduction in serum lamotrigine levels following ILE and continued reduction during hospitalization. The dog's clinical signs resolved, corrected QT interval returned to normal, and the patient was discharged 38 hr after presentation. Individual cases of lamotrigine toxicosis have not been fully reported in veterinary literature. This case report documents the rapid onset of clinical signs including neurologic dysfunction, cardiac arrhythmias, and transient corrected QT prolongation. Serial serum concentrations of lamotrigine showed a rapid reduction with ILE therapy and corresponded with clinical recovery, suggesting efficacy of ILE treatment in this case.}, number={4}, journal={Journal of the American Animal Hospital Association}, author={Hagley, Simon P and Epstein, Steven E and Stern, Joshua A and Poppenga, Robert}, year={2020}, pages={226—230} }
 @article{hansen_théon_willcox_stern_kent_2021, title={Long-term outcomes with conventional fractionated and stereotactic radiotherapy for suspected heart-base tumours in dogs}, volume={19}, url={https://escholarship.org/content/qt5d3346qv/qt5d3346qv.pdf?t=rvb7z0}, DOI={10.1111/vco.12662}, abstractNote={Abstract Published radiotherapy results for suspected heart‐based tumours in dogs are limited. In this retrospective longitudinal study (3/2014‐2019), eight dogs with either clinical signs attributable to a heart‐base mass (6), or asymptomatic with a progressively larger mass on echocardiogram (2), received conventional fractionated radiotherapy (CFRT) or stereotactic body radiotherapy (SBRT). Clinical findings in symptomatic cases included one or more of the following: retching/coughing (4), exercise intolerance (2), collapse (1), pericardial effusion (2), rare ventricular premature contractions (2), abdominal effusion (1), or respiratory distress due to chylothorax (1). CFRT cases received 50 Gray (Gy) in 20 fractions and SBRT cases received 30 Gy in 5 or 24 Gy in three fractions. Two dogs received chemotherapy post‐radiation. At analysis, 7/8 dogs were deceased and one was alive 684 days post‐treatment. The estimated median overall survival (MOS) from first treatment was 785 days (95% CI 114‐868 days, [range 114‐1492 days]). Five dogs received CFRT (MOS 817 days; (95% CI 155 days‐not reached [range 155‐1492 days])). Three dogs received SBRT with one alive at analysis (MOS 414 days, (95% CI, 114 days‐not reached [range 114‐414 days])). No statistically significant difference was found between survival for CFRT and SBRT. Of the symptomatic patients, 5/6 showed improvement. Mass size reduced in 4/5 cases receiving follow‐up ultrasounds. Possible complications included asymptomatic radiation pneumonitis (4), atrial tachycardia/premature beats (4) and pericardial effusion with heart failure coincident with tumour progression (1). This study provides preliminary evidence that radiotherapy may impact clinically relevant or progressively enlarging heart‐base masses.}, number={1}, journal={Veterinary and comparative oncology}, author={Hansen, Katherine S and Théon, Alain P and Willcox, Jennifer L and Stern, Joshua A and Kent, Michael S}, year={2021}, pages={191—200} }
 @article{cogné_latypova_senaratne_martin_koboldt_kellaris_fievet_le meur_caldari_debray_et al._2020, title={Mutations in the Kinesin-2 Motor KIF3B Cause an Autosomal-Dominant Ciliopathy}, volume={106}, ISSN={0002-9297}, url={http://dx.doi.org/10.1016/j.ajhg.2020.04.005}, DOI={10.1016/j.ajhg.2020.04.005}, abstractNote={Kinesin-2 enables ciliary assembly and maintenance as an anterograde intraflagellar transport (IFT) motor. Molecular motor activity is driven by a heterotrimeric complex comprised of KIF3A and KIF3B or KIF3C plus one non-motor subunit, KIFAP3. Using exome sequencing, we identified heterozygous <i>KIF3B</i> variants in two unrelated families with hallmark ciliopathy phenotypes. In the first family, the proband presents with hepatic fibrosis, retinitis pigmentosa, and postaxial polydactyly; he harbors a <i>de novo</i> c.748G>C (p.Glu250Gln) variant affecting the kinesin motor domain encoded by <i>KIF3B</i>. The second family is a six-generation pedigree affected predominantly by retinitis pigmentosa. Affected individuals carry a heterozygous c.1568T>C (p.Leu523Pro) <i>KIF3B</i> variant segregating in an autosomal-dominant pattern. We observed a significant increase in primary cilia length <i>in vitro</i> in the context of either of the two mutations while variant KIF3B proteins retained stability indistinguishable from wild type. Furthermore, we tested the effects of <i>KIF3B</i> mutant mRNA expression in the developing zebrafish retina. In the presence of either missense variant, rhodopsin was sequestered to the photoreceptor rod inner segment layer with a concomitant increase in photoreceptor cilia length. Notably, impaired rhodopsin trafficking is also characteristic of recessive <i>KIF3B</i> models as exemplified by an early-onset, autosomal-recessive, progressive retinal degeneration in Bengal cats; we identified a c.1000G>A (p.Ala334Thr) <i>KIF3B</i> variant by genome-wide association study and whole-genome sequencing. Together, our genetic, cell-based, and <i>in vivo</i> modeling data delineate an autosomal-dominant syndromic retinal ciliopathy in humans and suggest that multiple KIF3B pathomechanisms can impair kinesin-driven ciliary transport in the photoreceptor.}, number={6}, journal={The American Journal of Human Genetics}, publisher={Elsevier BV}, author={Cogné, Benjamin and Latypova, Xenia and Senaratne, Lokuliyanage Dona Samudita and Martin, Ludovic and Koboldt, Daniel C. and Kellaris, Georgios and Fievet, Lorraine and Le Meur, Guylène and Caldari, Dominique and Debray, Dominique and et al.}, year={2020}, month={Jun}, pages={893–904} }
 @article{graff_cochran_kaelin_day_gray-edwards_watanabe_koehler_falgoust_prokop_myers_et al._2020, title={PEA15 loss of function and defective cerebral development in the domestic cat.}, url={https://europepmc.org/articles/PMC7723247}, DOI={10.1371/journal.pgen.1008671}, abstractNote={Cerebral cortical size and organization are critical features of neurodevelopment and human evolution, for which genetic investigation in model organisms can provide insight into developmental mechanisms and the causes of cerebral malformations. However, some abnormalities in cerebral cortical proliferation and folding are challenging to study in laboratory mice due to the absence of gyri and sulci in rodents. We report an autosomal recessive allele in domestic cats associated with impaired cerebral cortical expansion and folding, giving rise to a smooth, lissencephalic brain, and that appears to be caused by homozygosity for a frameshift in PEA15 (phosphoprotein expressed in astrocytes-15). Notably, previous studies of a Pea15 targeted mutation in mice did not reveal structural brain abnormalities. Affected cats, however, present with a non-progressive hypermetric gait and tremors, develop dissociative behavioral defects and aggression with age, and exhibit profound malformation of the cerebrum, with a 45% average decrease in overall brain weight, and reduction or absence of the ectosylvian, sylvian and anterior cingulate gyrus. Histologically, the cerebral cortical layers are disorganized, there is substantial loss of white matter in tracts such as the corona radiata and internal capsule, but the cerebellum is relatively spared. RNA-seq and immunohistochemical analysis reveal astrocytosis. Fibroblasts cultured from affected cats exhibit increased TNFα-mediated apoptosis, and increased FGFb-induced proliferation, consistent with previous studies implicating PEA15 as an intracellular adapter protein, and suggesting an underlying pathophysiology in which increased death of neurons accompanied by increased proliferation of astrocytes gives rise to abnormal organization of neuronal layers and loss of white matter. Taken together, our work points to a new role for PEA15 in development of a complex cerebral cortex that is only apparent in gyrencephalic species.}, journal={PLoS genetics}, author={Graff, Emily and Cochran, Nick and Kaelin, Christopher and Day, Kenneth and Gray-Edwards, Heather and Watanabe, Rie and Koehler, Jennifer and Falgoust, Rebecca and Prokop, JW and Myers, Richard M. and et al.}, year={2020}, month={Dec} }
 @article{li_ontiveros_nguyen_stern_lee_hardy_2020, title={Precision medicine identifies a pathogenic variant of the <scp><i>ITGA2B</i></scp> gene responsible for Glanzmann's thrombasthenia in a cat}, volume={34}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/jvim.15886}, DOI={10.1111/jvim.15886}, abstractNote={AbstractBackgroundA nonpedigreed male cat presented with epistaxis, severe bladder hemorrhage, and secondary urethral obstruction after cystocentesis.ObjectivesTo characterize the phenotype of a cat with bleeding diathesis and use a precision medicine approach to identify the molecular genetic defect by whole genome sequencing.MethodsAdenosine diphosphate (ADP) and arachidonic acid (AA)‐induced whole blood platelet aggregometry was performed in the affected cat and a healthy cat. Platelet activation, measured by P‐selectin expression, and surface integrin subunit β3 expression were evaluated by flow cytometry in the affected cat and healthy control. Total integrin subunit αIIb expression was assessed by western blot. Whole genome sequencing at 30× coverage was used to identify genetic variants that segregated in the affected cat compared to 194 cats from the 99 Lives Sequencing Consortium.ResultsPlatelet aggregometry identified significant impairment in platelet aggregation in response to ADP and AA compared to the control cat. Targeted protein expression analyses by flow cytometry and immunoblot analysis determined that the surface expression and total expression of the integrin, αIIbβ3, was absent. Whole genome sequencing identified a homozygous c.1986delC frameshift variant in the integrin subunit αIIb (ITGA2B) gene that was not detected in the control population. The p.Pro662fs (ITGA2B P662X) variant terminates translation of the protein at the extracellular domain of the integrin prematurely, which is predicted to affect expression of the β3 unit.Conclusions and Clinical ImportanceThis novel ITGA2B variant and the associated phenotype closely resemble Glanzmann's thrombasthenia, which has never been reported in cats.}, number={6}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Li, Ronald H. L. and Ontiveros, Eric and Nguyen, Nghi and Stern, Joshua A. and Lee, Elizabeth and Hardy, Brian T.}, year={2020}, month={Sep}, pages={2438–2446} }
 @article{gunther-harrington_sharpe_vernau_ueda_montgomery_surmick_fernandez_ontiveros_walker_stern_2021, title={Reference intervals for radiographic, echocardiographic and N-terminal pro B-type natriuretic peptide values in healthy kittens}, volume={23}, ISSN={["1532-2750"]}, url={https://journals.sagepub.com/doi/pdf/10.1177/1098612X20946461}, DOI={10.1177/1098612x20946461}, abstractNote={Objectives Assessment of heart size in kittens is important, and there is a need for reference intervals (RIs) to prevent misinterpretation of cardiomegaly in this patient population. The purpose of this study was to generate RIs for echocardiographic and radiographic quantification of cardiac size in healthy kittens. Methods In total, 88 kittens aged 6–16 weeks were enrolled in this study. Physical examination, and radiographic and echocardiographic evaluations were performed without sedation. Thoracic radiographs and echocardiographic images were measured to establish RIs for vertebral heart score (VHS), cardiac thoracic ratio (CTR) and multiple echocardiographic variables. N-terminal pro B-type natriuretic peptide (NT-proBNP) was measured. Statistical correlations between echocardiographic parameters and age, body weight and sex were all evaluated and RIs were generated. Results Low-grade heart murmurs were appreciated in 26/88 kittens (29.5%). Kittens had a median VHS of 9.5 vertebrae (95% RI 8.0–10.9) and a median CTR of 67.2% (95% RI 54.4–79.8%). Measured NT-proBNP levels were comparable to healthy adult cats with a median of 31 pmol/l (upper reference limit 75 pmol/l). Multiple moderate-to-strong correlations between body weight and age with various echocardiographic parameters were observed and allometric scaling was performed for body weight. RIs for echocardiographic parameters were generated based on patient weight using allometric scaling formulas. Tricuspid valve regurgitation was a common finding and was present in 37.5% (n = 33) of the kittens. Conclusions and relevance This study establishes RIs for thoracic radiograph assessment, echocardiography and cardiac biomarkers in kittens, which fills a critical gap in the veterinary literature. The VHS reported in this study is higher than previously reported for adult cats. }, number={4}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Gunther-Harrington, Catherine T. and Sharpe, Ashley N. and Vernau, Karen M. and Ueda, Yu and Montgomery, Elizabeth A. and Surmick, Jennifer D. and Fernandez, Nicole and Ontiveros, Eric and Walker, Ashley L. and Stern, Joshua A.}, year={2021}, month={Apr}, pages={293–301} }
 @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://europepmc.org/articles/PMC7097578}, 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{fousse_stern_2020, title={Unraveling the Genetics Behind Equid Cardiac Disease}, volume={36}, url={https://doi.org/10.1016/j.cveq.2020.03.004}, DOI={10.1016/j.cveq.2020.03.004}, number={2}, journal={The Veterinary clinics of North America. Equine practice}, author={Fousse, Samantha L and Stern, Joshua A}, year={2020}, pages={235—241} }
 @article{fousse_golsen_sanchez-migallon guzman_paul-murphy_stern_2020, title={Varying Expression of Mu and Kappa Opioid Receptors in Cockatiels (<i>Nymphicus hollandicus</i>) and Domestic Pigeons (<i>Columba livia domestica)</i>}, volume={11}, url={https://europepmc.org/articles/PMC7593685}, DOI={10.3389/fgene.2020.549558}, abstractNote={Avian species have varying analgesic responses to opioid drugs. Some of this variability could be due to extrinsic factors such as administration route or dose. However, intrinsic factors such as gene expression or polymorphic differences in opioid receptors may be important components.The objectives of this study were to determine the relative gene expression and polymorphisms present for mu and kappa opioid receptors (OPRM1 and OPRK1) in the cerebrum, brainstem, spinal cord, and footpad of cockatiels and pigeons.Tissue biopsies were obtained from 11 adult cockatiels (6 male and 5 female) and 11 adult pigeons (6 male and 5 female). RNA was extracted and qPCR was performed to determine the level of gene expression for OPRM1 and OPRK1 relative to a reference gene phosphoglycerate kinase 1 (PGK1) using the ΔΔCt method. Sanger sequencing was performed to identify polymorphisms, if present.There were higher expression levels of OPRM1 compared to OPRK1 in all tissues examined regardless of species (p < 0.001, FDR p < 0.001) Cockatiels had less OPRK1 expression in the cerebrum compared to pigeons (p = 0.005, FDR p = 0.004). Cockatiels had more OPRM1 expression in the brainstem (p = 0.045, FDR p = 0.029), but less OPRM1 expression in the footpad compared to pigeons (p = 0.029, FDR p = 0.021). No other significant differences in OPRM1 or OPRK1 expression were identified across species. Two missense polymorphisms were identified in OPRK1; none were found in OPRM1.The differential expression of opioid receptors between cockatiels and pigeons could have implications for variability in analgesic response between these two species.}, journal={Frontiers in genetics}, author={Fousse, Samantha L and Golsen, Bryce M and Sanchez-Migallon Guzman, David and Paul-Murphy, Joanne R and Stern, Joshua A}, year={2020}, pages={549558} }
 @article{williams_ueda_stern_christe_2020, title={Vertebral Heart Score in Rhesus Macaques (Macaca mulatta): Generating Normal Reference Intervals and Assessing its Validity for Identifying Cardiac Disease}, volume={4}, url={https://europepmc.org/articles/PMC7338866}, DOI={10.30802/aalas-jaalas-19-000143}, abstractNote={Vertebral heart scoring (VHS) is a semiquantitative method to assess the presence and severity of cardiomegaly by usingthoracic radiographs. VHS in rhesus macaques (Macaca mulatta) has not been validated or used routinely in the clinical orresearch setting. We hypothesized that rhesus macaques with cardiac disease diagnosed by using echocardiography wouldhave higher VHS than animals without cardiac disease. A total of 150 rhesus macaques were enrolled in this study. All animalsunderwent echocardiography and thoracic radiography (right lateral [RL], dorsoventral [DV], and ventrodorsal [VD] views).According to echocardiography, 121 rhesus macaques had no cardiac disease and were used to establish reference intervalsfor VHS. The remaining 29 macaques had hypertrophic cardiomyopathy (n = 20) or other cardiac disease (n = 9). Resultsshowed that VHS of RL and VD views were significantly higher in macaques with any of the identified cardiac diseases andin the cardiac disease group that excluded hypertrophic cardiomyopathy. VHS of animals with HCM was not significantlydifferent than that of control animals. In the RL view, VHS was moderately accurate for predicting the presence of cardiacdisease, with an AUC of 0.71 and an optimal cut-off value of 10.25 (sensitivity: 62%, specificity: 77%). In the VD view, VHSwas a mildly accurate test for cardiac disease, with an AUC of 0.654 and an optimal cut-off value of 10.65 (sensitivity, 66%;specificity, 63%). Study results indicated that VHS could be a useful screening tool for clinically identifying rhesus macaqueswith cardiac disease. However, VHS is unlikely to replace echocardiographic examination for determining the presence, type,and severity of cardiac disease in this species.}, journal={Journal of the American Association for Laboratory Animal Science : JAALAS}, author={Williams, Amber R and Ueda, Yu and Stern, Joshua A and Christe, Kari L}, year={2020} }
 @article{buckley_gandolfi_creighton_pyne_bouhan_leroy_senter_gobble_abitbol_lyons_et al._2020, title={Werewolf, There Wolf: Variants in Hairless Associated with Hypotrichia and Roaning in the Lykoi Cat Breed}, volume={11}, ISSN={2073-4425}, url={http://dx.doi.org/10.3390/genes11060682}, DOI={10.3390/genes11060682}, abstractNote={A variety of cat breeds have been developed via novelty selection on aesthetic, dermatological traits, such as coat colors and fur types. A recently developed breed, the lykoi (a.k.a. werewolf cat), was bred from cats with a sparse hair coat with roaning, implying full color and all white hairs. The lykoi phenotype is a form of hypotrichia, presenting as a significant reduction in the average numbers of follicles per hair follicle group as compared to domestic shorthair cats, a mild to severe perifollicular to mural lymphocytic infiltration in 77% of observed hair follicle groups, and the follicles are often miniaturized, dilated, and dysplastic. Whole genome sequencing was conducted on a single lykoi cat that was a cross between two independently ascertained lineages. Comparison to the 99 Lives dataset of 194 non-lykoi cats suggested two variants in the cat homolog for Hairless (HR) (HR lysine demethylase and nuclear receptor corepressor) as candidate causal gene variants. The lykoi cat was a compound heterozygote for two loss of function variants in HR, an exon 3 c.1255_1256dupGT (chrB1:36040783), which should produce a stop codon at amino acid 420 (p.Gln420Serfs*100) and, an exon 18 c.3389insGACA (chrB1:36051555), which should produce a stop codon at amino acid position 1130 (p.Ser1130Argfs*29). Ascertainment of 14 additional cats from founder lineages from Canada, France and different areas of the USA identified four additional loss of function HR variants likely causing the highly similar phenotypic hair coat across the diverse cats. The novel variants in HR for cat hypotrichia can now be established between minor differences in the phenotypic presentations.}, number={6}, journal={Genes}, publisher={MDPI AG}, author={Buckley, Reuben M. and Gandolfi, Barbara and Creighton, Erica K. and Pyne, Connor A. and Bouhan, Delia M. and LeRoy, Michelle L. and Senter, David A. and Gobble, Johnny R. and Abitbol, Marie and Lyons, Leslie A. and et al.}, year={2020}, month={Jun}, pages={682} }
 @article{oldach_ueda_ontiveros_fousse_harris_stern_2019, title={Cardiac Effects of a Single Dose of Pimobendan in Cats With Hypertrophic Cardiomyopathy; A Randomized, Placebo-Controlled, Crossover Study.}, volume={6}, url={https://europepmc.org/articles/PMC6369151}, DOI={10.3389/fvets.2019.00015}, abstractNote={Background: Pimobendan has been shown to impart a significant survival benefit in cardiomyopathic cats who receive it as part of heart failure therapy. However, use of pimobendan remains controversial in cats with hypertrophic cardiomyopathy (HCM) due to lack of pharmacodynamic data for pimobendan in cats with HCM and due to theoretical concerns for exacerbating left ventricular outflow tract obstructions. Hypothesis/Objectives: Our objective was to investigate the cardiac effects of pimobendan in cats with HCM. We hypothesized that pimobendan would not exacerbate left ventricular outflow tract obstructions and that it would improve echocardiographic measures of diastolic function. Animals: Thirteen purpose-bred cats were studied from a research colony with naturally-occurring HCM due to a variant in myosin binding protein C. Methods: Cats underwent two examinations 24 h apart with complete standard echocardiography. On their first day of evaluation, they were randomized to receive oral placebo or 1.25 mg pimobendan 1 h prior to exam. On their second examination, they were crossed over and received the remaining treatment. Investigators were blinded to all treatments. Results: The pimobendan group had a significant increase in left atrial fractional shortening (pimobendan group 41.7% ± 5.9; placebo group 36.1% ± 6.0; p = 0.04). There was no significant difference in left ventricular outflow tract (LVOT) velocities between the groups (pimobendan group 2.8 m/s ± 0.8; placebo group 2.6 m/s ± 1.0). There were no significant differences between the number of cats with LVOT obstructions between groups (12 in pimobendan group; 11 in placebo group; p = 1.00). There were no detectable differences in any systolic measures, including left ventricular fractional shortening, mitral annular plane systolic excursion, and tricuspid annular plane systolic excursion. Doppler-based diastolic function assessment was precluded by persistent tachycardia. Conclusions: Improved left atrial function in the pimobendan group could explain some of the reported survival benefit for HCM cats in CHF. Pimobendan did not exacerbate LVOT obstructions and thus may not be contraindicated in HCM cats with LVOT obstructions. Future studies are needed to better characterize other physiologic effects, particularly regarding diastolic function assessment, and to better assess safety of pimobendan over a longer time-course.}, journal={Frontiers in Veterinary Science}, author={Oldach, Maureen S and Ueda, Yu and Ontiveros, Eric S and Fousse, Samantha L and Harris, Samantha P and Stern, Joshua A}, year={2019}, month={Feb}, pages={15} }
 @article{johnson_stern_2020, title={Clinical features and outcome in 25 dogs with respiratory-associated pulmonary hypertension treated with sildenafil}, volume={34}, url={https://europepmc.org/articles/PMC6979098}, DOI={10.1111/jvim.15679}, abstractNote={Pulmonary hypertension (PH) can develop secondary to many common cardiopulmonary diseases, and the use of sildenafil has improved care of affected dogs.To evaluate response to sildenafil in dogs with respiratory-associated PH.Twenty-five dogs with PH.Prospective clinical trial. Doppler echocardiography identified dogs with moderate to severe PH, and additional tests were performed to detect underlying diseases. A 17-point quality of life (QOL) questionnaire was completed, and sildenafil was prescribed, along with other medications deemed necessary for the management of clinically diagnosed respiratory diseases. After 30 days, dogs returned to the hospital for repeat echocardiogram and QOL survey.The median age was 12.4 years, and most dogs were small breed dogs (median weight, 6.5 kg). Syncope (64%), cough (56%), and respiratory difficulty (32%) were the most common presenting complaints. Respiratory diseases associated with PH included tracheobronchomalacia, pulmonary fibrosis, inflammatory airway disease, and brachycephalic syndrome, with multiple diseases in some dogs. Eight of 25 dogs (32%) died or were euthanized within 1 month. In the remaining dogs, tricuspid regurgitation pressure gradient (83.0 ± 17.4 mm Hg before, 55.4 ± 17.4 mm Hg after) and QOL scores were significantly improved after 1 month of sildenafil. Fifty percent mortality was reached 6 months after study entry, with 4 dogs alive 5 years after diagnosis.Sildenafil responsiveness is variable in dogs with respiratory-associated PH, but improved QOL was demonstrated in dogs surviving >1 month, and long-term survival was noted in some cases.}, number={1}, journal={Journal of veterinary internal medicine}, author={Johnson, Lynelle R and Stern, Joshua A}, year={2020}, pages={65—73} }
 @article{ontiveros_fousse_crofton_hodge_gunther-harrington_visser_stern_2019, title={Congenital Cardiac Outflow Tract Abnormalities in Dogs: Prevalence and Pattern of Inheritance From 2008 to 2017}, volume={6}, url={https://europepmc.org/articles/PMC6402372}, DOI={10.3389/fvets.2019.00052}, abstractNote={Subvalvular aortic stenosis (SAS) and valvular pulmonic stenosis (PS) are two of the most common congenital heart diseases of dogs. The aim of this study was to determine the prevalence and mode of inheritance of these congenital heart diseases in a large veterinary teaching hospital population. Case records of dogs presented to the University of California Davis, Veterinary Medical Teaching Hospital (UCD VMTH) between January 2008 to December 2017 were reviewed retrospectively and pedigree information was obtained when available. There were 259 unique SAS and 336 unique PS cases diagnosed during the study period. The prevalence of SAS was 0.3% of overall hospital admissions and 4.7% for all dogs seen by the cardiology service. The prevalence for PS was 0.41% of overall hospital admissions and 6.1% of dogs seen by the cardiology service. Bullmastiffs and Newfoundlands had the greatest prevalence (6.59% and 4.46% respectively) and odds ratio (52.43 and 34.73 respectively) for SAS. Bulldogs and French Bulldogs had the greatest prevalence (4.8% and 2.7% respectively) and odds ratio (13.32 and 7.52 respectively) for PS. The identified prevalence of SAS and PS is higher than previously reported. Pedigree analysis in SAS affected Bullmastiffs, Golden Retrievers, and Rottweilers suggested an autosomal recessive pattern of inheritance. The mode of inheritance for PS in Bulldogs, also appears to be autosomal recessive. The results of this study can be used to inform future selection of breeding pairs and genetic studies aimed at reducing the prevalence of these common congenital heart diseases.}, journal={Frontiers in veterinary science}, author={Ontiveros, Eric S and Fousse, Samantha L and Crofton, Amanda E and Hodge, Timothy E and Gunther-Harrington, Catherine T and Visser, Lance C and Stern, Joshua A}, year={2019}, pages={52} }
 @article{nishimura_visser_gunther-harrington_ueda_stern_2019, title={ECG of the Month}, volume={255}, url={https://doi.org/10.2460/javma.255.1.60}, DOI={10.2460/javma.255.1.60}, number={1}, journal={Journal of the American Veterinary Medical Association}, author={Nishimura, Satoko and Visser, Lance C and Gunther-Harrington, Catherine T and Ueda, Yu and Stern, Joshua A}, year={2019}, pages={60—62} }
 @article{visser_nishimura_oldach_bélanger_gunther-harrington_stern_hsue_2019, title={Echocardiographic assessment of right heart size and function in dogs with pulmonary valve stenosis}, volume={26}, url={https://doi.org/10.1016/j.jvc.2019.11.002}, DOI={10.1016/j.jvc.2019.11.002}, journal={Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology}, author={Visser, LC and Nishimura, S and Oldach, MS and Bélanger, C and Gunther-Harrington, CT and Stern, JA and Hsue, W}, year={2019}, pages={19—28} }
 @article{ueda_johnson_ontiveros_visser_gunther-harrington_stern_2019, title={Effect of a phosphodiesterase-5A (PDE5A) gene polymorphism on response to sildenafil therapy in canine pulmonary hypertension}, volume={9}, url={https://europepmc.org/articles/PMC6499771}, DOI={10.1038/s41598-019-43318-z}, abstractNote={Abstract Pulmonary hypertension (PH) is a common clinical condition associated with morbidity and mortality in both humans and dogs. Sildenafil, a phosphodiesterase-5 (PDE5) inhibitor causing accumulation of cGMP, is frequently used for treatment of PH. The authors previously reported a PDE5A :E90K polymorphism in dogs that results in lower basal cyclic guanosine monophosphate (cGMP) concentrations than in wild-type dogs, which could contribute to variability in the efficacy of sildenafil. In this study, response to sildenafil therapy was evaluated in dogs with PH by comparing echocardiographic parameters, quality-of-life (QOL) score, and plasma cGMP concentrations before and after sildenafil therapy. Overall, tricuspid regurgitation estimated systolic pressure gradient (PG) and QOL score were significantly improved after sildenafil therapy, and the plasma cGMP concentration was significantly decreased. Dogs that had a heterozygous PDE5A status had a significantly worse QOL score when compared to the wildtype group after sildenafil treatment. The simple and multiple regression analyses revealed a significant but weak prediction for the percent reduction in QOL score with sildenafil treatment by plasma cGMP level and by the PDE5A :E90K polymorphic status. This study showed that sildenafil treatment improved PH in dogs, and the PDE5A :E90K polymorphism blunted the efficacy of sildenafil in terms of QOL improvement.}, number={1}, journal={Scientific reports}, author={Ueda, Yu and Johnson, Lynelle R and Ontiveros, Eric S and Visser, Lance C and Gunther-Harrington, Catherine T and Stern, Joshua A}, year={2019}, pages={6899} }
 @article{ontiveros_hughes_penedo_grahn_stern_2019, title={Genetic heterogeneity and diversity of North American golden retrievers using a low density STR marker panel}, volume={14}, url={https://europepmc.org/articles/PMC6392251}, DOI={10.1371/journal.pone.0212171}, abstractNote={Thirty-three autosomal short tandem repeat (STR) markers were used to evaluate genetic heterogeneity and diversity in 525 golden retrievers (GRs). This breed was selected because of its popularity and artificial selection for conformation vs. performance phenotypes. Seven additional STRs were used to evaluate the highly polymorphic dog leukocyte antigen (DLA) class I and class II regions. From 3 to 13 alleles were found at each of the 33 loci (mean 7) and the average effective alleles (Ne) was 3.34. The observed heterozygosity was 0.65 and the expected heterozygosity was 0.68. The resulting fixation index was 0.035 indicating that the population was randomly breeding. We found that modern GRs retain 46% of genomic diversity present in all canids and 21/175 (12%) and 20/90 (22%) of the known DLA class I and class II haplotypes, respectively. Selection for performance or conformation led to a narrowing of genomic and DLA diversity with conformation having a greater effect than performance. A comparison was made between coefficient of inbreeding (COI) determined from 10 or 12 generation pedigrees and DNA based internal relatedness values. A weak but significant correlation was observed between IR score and 10 or 12 generation COI (r = 0.38, p<0.0001 and r = 0.40, p<0.0001, respectively). IR values were higher in conformation than performance lines but only significant at p = 0.17. This was supported by 10 and 12 generation COI values that were significantly (p<0.0001) higher in conformation than performance lines. We demonstrate herein that a low density of STR markers can be utilized to study the genetic makeup of GRs.}, number={2}, journal={PloS one}, author={Ontiveros, Eric S and Hughes, Shayne and Penedo, Maria Cecilia T and Grahn, Robert A and Stern, Joshua A}, editor={Chiang, Tzen-YuhEditor}, year={2019}, pages={e0212171} }
 @article{ueda_slabaugh_walker_ontiveros_sosa_reader_roberts_stern_2019, title={Heart Rate and Heart Rate Variability of Rhesus Macaques (Macaca mulatta) Affected by Left Ventricular Hypertrophy}, volume={6}, url={https://europepmc.org/articles/PMC6349711}, DOI={10.3389/fvets.2019.00001}, abstractNote={Hypertrophic cardiomyopathy (HCM) is frequently associated with sudden cardiac death, presumably due to the development of malignant arrhythmias. The risk of sudden cardiac death due to HCM has been reported to be predicted by assessing electrocardiographic (ECG) changes including frequencies and complexities of arrhythmias as well as heart rate variability (HRV) as an assessment of autonomic balance. Sudden cardiac death in association with naturally-occurring left ventricular hypertrophy (LVH) has been reported in a colony of rhesus macaques and is under investigation as a potential non-human primate model of human HCM. In the present study, 10 rhesus macaques with LVH and 10 without the signs of LVH confirmed by an echocardiographic examination were recruited for assessing ECG and HRV parameters. ECG morphology on 10-s, 6-lead ECG analysis, and the frequency and complexity of arrhythmias as well as HRV on 20-h ambulatory ECG Holter analyses were assessed. On the standard 10-s 6-lead ECG analysis, P wave and QRS complex duration as well as the QRS complex amplitude were significantly increased in the LVH-affected rhesus macaques compared to control rhesus macaques. Analysis of 20-h Holter monitoring revealed no statistically significant differences in the frequency or the complexity of arrhythmias between the LVH and the control groups. Several HRV parameters were smaller in the LVH group than the control group throughout the majority of Holter recordings showing periods of reduced variability, however, no statistically significant differences were achieved across groups and/or time points. These findings indicate that ECG analysis and Holter monitoring of rhesus macaques are feasible and that ECG morphological changes in association with LVH could be used as a possible component of an antemortem screening tool. The rhesus macaques of this study did not reveal clear indications of risk for sudden cardiac death. Further studies are necessary to determine the etiology of sudden cardiac death due in LVH affected rhesus macaques and identify if any parameters of arrhythmia assessment or HRV can be used to predict the development of sudden cardiac death.}, journal={Frontiers in veterinary science}, author={Ueda, Yu and Slabaugh, Taylor L and Walker, Ashley L and Ontiveros, Eric S and Sosa, Paul-Michael and Reader, Rachel and Roberts, Jeffrey A and Stern, Joshua A}, year={2019}, pages={1} }
 @article{fousse_tyrrell_dentino_abrams_rosenthal_stern_2019, title={Pedigree analysis of atrial fibrillation in Irish wolfhounds supports a high heritability with a dominant mode of inheritance}, volume={6}, url={https://europepmc.org/articles/PMC6902490}, DOI={10.1186/s40575-019-0079-y}, abstractNote={Atrial fibrillation (AF) is the most common arrhythmia in dogs. The Irish Wolfhound breed has a high prevalence of AF making them an ideal breed to investigate possible genetic contributions to this disease. The aim of this study was to perform a heritability analysis in North American Irish Wolfhounds using phenotype data from cardiac screenings performed between 2000 and 2019 in order to determine how much of this disease can be attributed to genetics compared to environmental causes. The second aim was to determine the disease mode of inheritance to help inform prevention and breeding practices.There were 327 Irish Wolfhounds diagnosed with AF and 136 Irish Wolfhounds over 8 years of age without AF. The estimated mean (95% confidence interval) heritability of AF in Irish Wolfhounds was 0.69 (0.50-0.86). The pedigree was consistent with a dominant mode of inheritance.Results of this study indicate a strong genetic contribution to AF in Irish Wolfhounds and suggest that future research to identify causative genetic mutations is warranted.}, journal={Canine genetics and epidemiology}, author={Fousse, Samantha L and Tyrrell, William D and Dentino, Mariellen E and Abrams, Frances L and Rosenthal, Steven L and Stern, Joshua A}, year={2019}, pages={11} }
 @article{oldach_gunther-harrington_balsa_mclarty_wakeman_phillips_honkavaara_visser_stern_2018, title={Aberrant migration and surgical removal of a heartworm (Dirofilaria immitis) from the femoral artery of a cat}, volume={32}, url={https://europepmc.org/articles/PMC5866988}, DOI={10.1111/jvim.15070}, abstractNote={A cat was evaluated for an acute‐onset of right pelvic limb paresis. Thoracic radiographs revealed normal cardiac size and tortuous pulmonary arteries. Abdominal ultrasound identified a heartworm (HW) extending from the caudal abdominal aorta into the right external iliac artery and right femoral artery. The cat was HW‐antigen positive. Echocardiography revealed a HW within the right branch of the main pulmonary artery and evidence of pulmonary hypertension. An agitated‐saline contrast echocardiogram revealed a small right to left intracardiac shunt at the level of the atria. Surgical removal of the HW was performed with no substantial postoperative complications. There was return of blood flow and improved motor function to the limb. The cat remains mildly paretic on the affected limb with no other clinical signs.}, number={2}, journal={Journal of veterinary internal medicine}, author={Oldach, Maureen S and Gunther-Harrington, Catherine T and Balsa, Ingrid M and McLarty, Ehren M and Wakeman, Kyle A and Phillips, Kathryn L and Honkavaara, Juhana and Visser, Lance C and Stern, Joshua A}, year={2018}, pages={792—796} }
 @article{visser_kaplan_nishimura_gunther-harrington_bélanger_oldach_stern_mueller_2018, title={Acute echocardiographic effects of sotalol on ventricular systolic function in dogs with ventricular arrhythmias}, volume={32}, url={https://europepmc.org/articles/PMC6060330}, DOI={10.1111/jvim.15224}, abstractNote={Background Sotalol is a commonly used antiarrhythmic drug that may alter ventricular function. Objective To determine the effect of sotalol on echocardiographic indices of ventricular systolic function in dogs with ventricular arrhythmias. Animals Thirty‐five client‐owned dogs with ventricular arrhythmias. Methods Dogs with ventricular arrhythmias (n = 27) had an echocardiogram and 5‐minute ECG performed at baseline and 2‐4 hours post‐sotalol (2‐2.5 mg/kg PO once). Eight additional dogs underwent the same protocol but did not receive sotalol (within‐day variability controls). Left ventricular (LV) internal dimension at end‐systole normalized to bodyweight (LVIDs_N), LV ejection fraction (LV EF), LV shortening area, LV fractional shortening, tricuspid annular plane systolic excursion (TAPSE), and right ventricular systolic myocardial velocity were evaluated as indices of systolic function. Results All indices except TAPSE had mild decreases in systolic function post‐sotalol (all P ≤ .0007) compared with baseline but only the percent change in LVIDs_N and LV EF were significantly ( P ≤ .0079) different from the percent change of the same indices in control dogs. Sinus heart rate, ventricular premature complexes/5‐minutes, and arrhythmia grade also were decreased post‐sotalol (all P ≤ .01) compared with baseline when assessed by a 5‐minutes ECG. No dog experienced an adverse event post‐sotalol, including dogs with systolic dysfunction or atrial enlargement. Conclusions and Clinical Importance A single dose of sotalol may cause a mild decrease in LV systolic function in dogs with ventricular arrhythmias. Sotalol appears to be well tolerated, even in dogs with atrial enlargement or systolic dysfunction.}, number={4}, journal={Journal of veterinary internal medicine}, author={Visser, Lance C and Kaplan, Joanna L and Nishimura, Satoko and Gunther-Harrington, Catherine T and Bélanger, Catherine and Oldach, Maureen S and Stern, Joshua A and Mueller, Mikaela S}, year={2018}, pages={1299—1307} }
 @article{kaplan_stern_fascetti_larsen_skolnik_peddle_kienle_waxman_cocchiaro_gunther-harrington_et al._2018, title={Correction: Taurine deficiency and dilated cardiomyopathy in golden retrievers fed commercial diets}, volume={13}, url={https://europepmc.org/articles/PMC6312369}, DOI={10.1371/journal.pone.0210233}, abstractNote={[This corrects the article DOI: 10.1371/journal.pone.0209112.].}, number={12}, journal={PloS one}, author={Kaplan, Joanna L and Stern, Joshua A and Fascetti, Andrea J and Larsen, Jennifer A and Skolnik, Hannah and Peddle, Gordon D and Kienle, Richard D and Waxman, Andrew and Cocchiaro, Michael and Gunther-Harrington, Catherine T and et al.}, year={2018}, pages={e0210233} }
 @article{freeman_stern_fries_adin_rush_2018, title={Diet-associated dilated cardiomyopathy in dogs: what do we know?}, volume={253}, url={https://avmajournals.avma.org/doi/pdf/10.2460/javma.253.11.1390}, DOI={10.2460/javma.253.11.1390}, number={11}, journal={Journal of the American Veterinary Medical Association}, author={Freeman, Lisa M and Stern, Joshua A and Fries, Ryan and Adin, Darcy B and Rush, John E}, year={2018}, pages={1390—1394} }
 @article{nishimura_visser_bélanger_oldach_gunther-harrington_stern_2018, title={Echocardiographic evaluation of velocity ratio, velocity time integral ratio, and pulmonary valve area in dogs with pulmonary valve stenosis}, volume={32}, url={https://europepmc.org/articles/PMC6189360}, DOI={10.1111/jvim.15244}, abstractNote={Background Velocity ratio, velocity time integral (VTI) ratio, and pulmonary valve area indexed to body surface area (iPVA) are methods of assessment of pulmonary valve stenosis (PS) severity that are less dependent on blood flow. Studies evaluating these methods are limited. Objectives To determine the effects of butorphanol, atenolol, and balloon valvuloplasty (BV) on velocity ratio, VTI ratio, iPVA, mean PG, and max PG. Animals Twenty‐seven dogs with PS (max PG >50 mm Hg). Methods Prospective study. All dogs underwent an echocardiogram at baseline, 5‐minutes after administration of butorphanol (0.2‐0.25 mg/kg IV), and 2‐to‐4 weeks after atenolol (1‐1.5 mg/kg q12h). Twenty‐one of these were evaluated 24‐hours after BV. Results There were no significant differences ( P > .05) amongst any of the methods of assessment of PS severity after butorphanol. After atenolol, mean (SD) of mean (57.0 [21.0] mm Hg) and max PG (93.1 [33.8] mm Hg) were significantly decreased ( P ≤ .047) compared with baseline (65.2 [26.2] mm Hg and 108 [44.4] mm Hg, respectively). After atenolol, there were no significant ( P ≥ .12) differences in velocity ratio (0.29 [0.09]), VTI ratio (0.18 [0.05]), or iPVA (0.43 [0.16] cm 2 /m 2 ) compared with baseline (0.30 [0.09], 0.19 [0.09], 0.44 [0.17] cm 2 /m 2 , respectively). Conclusions and Clinical Importance Atenolol might reduce mean and max PG but does not alter less flow‐dependent methods of assessment of PS severity (velocity ratio, VTI ratio, and iPVA) in dogs with PS. Results support an integrative approach to assessment of PS severity that includes less flow‐dependent methods, particularly in states of altered flow or right ventricular function.}, number={5}, journal={Journal of veterinary internal medicine}, author={Nishimura, Satoko and Visser, Lance C and Bélanger, Catherine and Oldach, Maureen S and Gunther-Harrington, Catherine T and Stern, Joshua A}, year={2018}, pages={1570—1578} }
 @article{genova_longeri_lyons_bagnato_strillacci_2018, title={First genome-wide CNV mapping in FELIS CATUS using next generation sequencing data}, volume={19}, url={https://europepmc.org/articles/PMC6288940}, DOI={10.1186/s12864-018-5297-2}, abstractNote={Copy Number Variations (CNVs) have becoming very significant variants, representing a major source of genomic variation. CNVs involvement in phenotypic expression and different diseases has been widely demonstrated in humans as well as in many domestic animals. However, genome wide investigation on these structural variations is still missing in Felis catus. The present work is the first CNV mapping from a large data set of Next Generation Sequencing (NGS) data in the domestic cat, performed within the 99 Lives Consortium.Reads have been mapped on the reference assembly_6.2 by Maverix Biomics. CNV detection with cn.MOPS and CNVnator detected 592 CNVs. These CNVs were used to obtain 154 CNV Regions (CNVRs) with BedTools, including 62 singletons. CNVRs covered 0.26% of the total cat genome with 129 losses, 19 gains and 6 complexes. Cluster Analysis and Principal Component Analysis of the detected CNVRs showed that breeds tend to cluster together as well as cats sharing the same geographical origins. The 46 genes identified within the CNVRs were annotated.This study has improved the genomic characterization of 14 cat breeds and has provided CNVs information that can be used for studies of traits in cats. It can be considered a sound starting point for genomic CNVs identification in this species.}, number={1}, journal={BMC genomics}, author={Genova, F and Longeri, M and Lyons, LA and Bagnato, A and Strillacci, MG}, year={2018}, pages={895} }
 @article{belanger_gunther-harrington_nishimura_oldach_fousse_visser_stern_2018, title={High-pressure balloon valvuloplasty for severe pulmonary valve stenosis: a prospective observational pilot study in 25 dogs}, volume={20}, url={https://doi.org/10.1016/j.jvc.2018.01.001}, DOI={10.1016/j.jvc.2018.01.001}, number={2}, journal={Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology}, author={Belanger, Catherine and Gunther-Harrington, Catherine T and Nishimura, Satoko and Oldach, Maureen S and Fousse, Samantha L and Visser, Lance C and Stern, Joshua A}, year={2018}, pages={115—122} }
 @article{stern_ueda_2019, title={Inherited cardiomyopathies in veterinary medicine}, volume={471}, url={https://doi.org/10.1007/s00424-018-2209-x}, DOI={10.1007/s00424-018-2209-x}, number={5}, journal={Pflugers Archiv : European journal of physiology}, publisher={Springer Science and Business Media LLC}, author={Stern, Joshua A and Ueda, Yu}, year={2019}, pages={745—753} }
 @article{kaplan_gunther-harrington_sutton_stern_2018, title={Multiple midline defects identified in a litter of golden retrievers following gestational administration of prednisone and doxycycline: a case series}, volume={14}, url={https://europepmc.org/articles/PMC5848590}, DOI={10.1186/s12917-018-1419-y}, abstractNote={The teratogenic effects of immunomodulatory and certain antimicrobial therapies are described in small rodents and humans. While the described teratogenic effects in small rodents have been extrapolated to make conclusions about its use in the pregnant dam, teratogenic effects of prednisone and doxycycline have not yet been reported in the dog. Here we report and describe midline defects observed in a litter of golden retriever puppies exposed to mid-gestational immunosuppressive and antimicrobial therapy. Twenty-one days into gestation, the dam of a litter of eight golden retriever puppies was administered prednisone, doxycycline, and tramadol as treatment for immune-mediated polyarthritis. The individuals in the litter were subsequently diagnosed with a variety of midline defects and congenital cardiac defects. This case series describes the variety of identified defects and presents a descriptive account of complex congenital abnormalities that are likely secondary to teratogenic effects of one or more drugs administered during gestation. The available puppies, dam, and grand dam underwent thorough physical examination, complete echocardiogram, and where indicated, advanced imaging with various surgical corrections when possible. Numerous midline congenital defects and congenital heart disease were identified in the puppies evaluated. Ultimately 5 of 8 puppies born to the dam were presented for thorough evaluation. The midline defects include: gastroschisis (1), peritoneopericardial diaphragmatic hernias (4, PPDH), umbilical hernia (4), unilateral cryptorchidism (1 of 4 males), cleft palate (1), renal agenesis (1), renal abnormalities (1), sternal and vertebral abnormalities (3), remnant liver lobe (1) and malformations consistent with ductal plate malformations with congenital hepatic fibrosis (1). The congenital cardiac defects include: ventricular septal defect (4, VSD) and subaortic stenosis (4, SAS). The presence of greater than one congenital defect was noted in all 5 of the dogs evaluated. Surgical correction was necessary for PPDH in 4 puppies. Medical intervention was recommended for congenital cardiac disease in 1 puppy. This case report is the first to describe midline defects in dogs that have been exposed to immunomodulatory therapy during gestation. A causative relationship between mid-gestational immunomodulatory exposure and midline defects cannot be proven, however, this case supports a clear association and provides case-based evidence to support its avoidance when possible.}, number={1}, journal={BMC veterinary research}, publisher={Springer Nature}, author={Kaplan, Joanna L and Gunther-Harrington, Catherine T and Sutton, Jessie S and Stern, Joshua A}, year={2018}, pages={86} }
 @article{gunther-harrington_phillips_visser_fousse_stern_2019, title={Non-electrocardiographic-gated computed tomographic angiography can be used to diagnose coronary artery anomalies in Bulldogs with pulmonary valve stenosis}, volume={60}, url={https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/vru.12689}, DOI={10.1111/vru.12689}, abstractNote={Abstract Coronary artery anomalies have been reported in Bulldogs and present an increased risk when performing balloon valvuloplasty. Identification of coronary anomalies has been reported using multidetector‐row computed tomographic (MDCT) angiography with electrocardiographic gating. However, the utility of non‐electrocardiographic‐gated 16‐row computed tomographic for MDCT for the identification of coronary artery anatomy or anomalies to the authors’ knowledge has not been fully investigated. The purpose of this study was to evaluate the feasibility of non‐electrocardiographic‐gated computed tomographic (CT) angiography to identify coronary anomalies in Bulldogs with pulmonary valve stenosis. In this prospective, observational study, Bulldogs with echocardiographically diagnosed pulmonary valve stenosis, an echocardiographically derived transpulmonic pressure gradient >70 mm Hg, and a clinician recommendation for balloon valvuloplasty were included. Anesthetized dogs underwent a 16‐row MDCT non‐electrocardiographic‐gated CT angiography. A board‐certified veterinary radiologist and board‐certified veterinary cardiologist reviewed the CT angiography studies and identified the coronary artery anatomy. When normal coronary artery anatomy was detected on CT angiography, a right ventricular outflow tract fluoroscopic angiogram was performed and evaluated during levophase to confirm normal coronary anatomy prior to balloon valvuloplasty. Dogs with coronary anomalies noted on CT angiography were recovered from anesthesia and balloon valvuloplasty was not performed. All dogs (10/10; 100%) had interpretable images from the non‐electrocardiographic‐gated CT angiography. Coronary anomalies were identified in six dogs based on non‐electrocardiographic‐gated CT angiography, five with type R2A anomaly and one had a single left coronary ostium. Four dogs had normal coronary anatomy based on non‐electrocardiographic‐gated CT angiography. Balloon valvuloplasty was performed without incident in these four dogs. We conclude that non‐electrocardiographic‐gated CT angiography represents a noninvasive method for diagnosing coronary anomalies in Bulldogs with pulmonary valve stenosis.}, number={1}, journal={Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association}, author={Gunther-Harrington, Catherine T and Phillips, Kathryn L and Visser, Lance C and Fousse, Samantha L and Stern, Joshua A}, year={2019}, pages={38—46} }
 @article{ueda_li_tablin_ontiveros_stern_2018, title={Nonsynonymous single nucleotide polymorphisms in candidate genes <i>P2<scp>RY</scp>1</i>,<i> P2<scp>RY</scp>12</i> and <i><scp>CYP</scp>2C19</i> for clopidogrel efficacy in cats}, volume={49}, ISSN={0268-9146 1365-2052}, url={http://dx.doi.org/10.1111/age.12666}, DOI={10.1111/age.12666}, 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={4}, journal={Animal Genetics}, publisher={Wiley}, author={Ueda, Yu and Li, Ronald Hak Long and Tablin, Fern and Ontiveros, Eric S. and Stern, Joshua A.}, year={2018}, month={May}, pages={356–357} }
 @article{ontiveros_ueda_harris_stern_lyons_gandolfi_aberdein_garrick_munday_alves_et al._2019, title={Precision medicine validation: identifying the MYBPC3 A31P variant with whole-genome sequencing in two Maine Coon cats with hypertrophic cardiomyopathy}, volume={21}, ISSN={["1532-2750"]}, url={https://doi.org/10.1177/1098612X18816460}, DOI={10.1177/1098612x18816460}, abstractNote={Objectives The objective of this study was to perform a proof-of-concept experiment that validates a precision medicine approach to identify variants associated with hypertrophic cardiomyopathy (HCM). We hypothesized that whole-genome sequencing would identify variant(s) associated with HCM in two affected Maine Coon/Maine Coon cross cats when compared with 79 controls of various breeds. Methods Two affected and two control Maine Coon/Maine Coon cross cats had whole-genome sequencing performed at approximately × 30 coverage. Variants were called in these four cats and 77 cats of various breeds as part of the 99 Lives Cat Genome Sequencing Initiative ( http://felinegenetics.missouri.edu/99lives ) using Platypus v0.7.9.1, annotated with dbSNP ID, and variants’ effect predicted by SnpEff. Strict filtering criteria (alternate allele frequency >49%) were applied to identify homozygous-alternate or heterozygous variants in the two HCM-affected samples when compared with 79 controls of various breeds. Results A total of four variants were identified in the two Maine Coon/Maine Coon cross cats with HCM when compared with 79 controls after strict filtering. Three of the variants identified in genes MFSD12, BTN1A1 and SLITRK5 did not segregate with disease in a separate cohort of seven HCM-affected and five control Maine Coon/Maine Coon cross cats. The remaining variant MYBPC3 segregated with disease status. Furthermore, this gene was previously associated with heart disease and encodes for a protein with sarcomeric function. Conclusions and relevance This proof-of-concept experiment identified the previously reported MYBPC3 A31P Maine Coon variant in two HCM-affected cases. This result validates and highlights the power of whole-genome sequencing for feline precision medicine. }, number={12}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Ontiveros, Eric S. and Ueda, Yu and Harris, Samantha P. and Stern, Joshua A. and Lyons, Leslie A. and Gandolfi, Barbara and Aberdein, Danielle and Garrick, Dorian J. and Munday, John S. and Alves, Paulo C. and et al.}, year={2019}, month={Dec}, pages={1086–1093} }
 @article{gunther-harrington_arthur_estell_lopez_sinnott_ontiveros_varga_stern_2018, title={Prospective pre- and post-race evaluation of biochemical, electrophysiologic, and echocardiographic indices in 30 racing thoroughbred horses that received furosemide}, volume={14}, url={https://doi.org/10.1186/s12917-018-1336-0}, DOI={10.1186/s12917-018-1336-0}, abstractNote={Exercise induced cardiac fatigue (EICF) and cardiac dysrhythmias are well described conditions identified in high-level human athletes that increase in frequency with intensity and duration of exercise. Identification of these conditions requires an understanding of normal pre- and post-race cardiac assessment values. The objectives of this study were to (1) characterize selected indices of cardiac function, electrophysiologic parameters, and biochemical markers of heart dysfunction prior to and immediately after high level racing in Thoroughbred horses receiving furosemide; and (2) create pre- and post-race reference values in order to make recommendations on possible screening practices for this population in the future. Thirty Thoroughbred horses were enrolled in the study with an age range of 3–6 years. All horses received furosemide prior to racing. Physical exams, ECGs, and echocardiograms were performed prior to racing (T0) and within 30–60 min following the race (T1). Blood samples were obtained at T0, T1, 4 h post-race (T4) and 24 h after the race (T24). Electrolytes, hematocrit, cardiac troponin I, and partial pressure CO2 values were obtained at all time points. Heart rate was significantly increased post-race compared to baseline value with a median difference of 49 bpm, 95% CI [31,58],(P < 0.0001). No dysrhythmias were noted during ECG assessment. Following the race, an increase in number of horses demonstrating regurgitation through the aorta and AV valves was noted. Systolic function measured by fractional shortening increased significantly with a mean difference of 7.9%, 95% CI [4.8, 10.9], (P < 0.0001). Cardiac troponin I was not different at pre- and immediately post-race time points, but was significantly increased at T4 (P < 0.001). Troponin returned to baseline value by T24. This study utilized a before and after study design where each horse served as its own control, as such the possible effect of regression to the mean cannot be ruled out. The reference intervals generated in this study may be used to identify selected echocardiographic and electrocardiographic abnormalities in racing horses receiving furosemide.}, number={1}, journal={BMC Veterinary Research}, publisher={Springer Nature}, author={Gunther-Harrington, Catherine T. and Arthur, Rick and Estell, Krista and Lopez, Beatriz Martinez and Sinnott, Alexandra and Ontiveros, Eric and Varga, Anita and Stern, Joshua A.}, year={2018}, month={Dec}, pages={18} }
 @article{kaplan_stern_fascetti_larsen_skolnik_peddle_kienle_waxman_cocchiaro_gunther-harrington_et al._2018, title={Taurine deficiency and dilated cardiomyopathy in golden retrievers fed commercial diets}, volume={13}, url={https://europepmc.org/articles/PMC6292607}, DOI={10.1371/journal.pone.0209112}, abstractNote={Golden retrievers are over-represented in cases of taurine-deficient dilated cardiomyopathy and recently a surge in cases has prompted further investigation.To describe the clinical, dietary, and echocardiographic features in golden retrievers diagnosed with taurine deficiency and dilated cardiomyopathy, and to determine specific dietary associations. A second aim was to determine the whole blood taurine concentrations in a representative sample of healthy golden retrievers.Twenty-four client-owned golden retrievers with documented taurine deficiency and dilated cardiomyopathy and 52 healthy client-owned golden retrievers.In this multicenter prospective observational study, baseline and follow-up echocardiographic data, complete diet and medical histories, and whole blood, plasma, or serum taurine concentrations were obtained. Baseline and follow-up echocardiographic data were compared. Associations were evaluated between specific diets and taurine deficiency or congestive heart failure. The prevalence of low whole blood taurine concentrations in the healthy golden retrievers was calculated.Twenty-three of 24 dogs diagnosed with taurine deficiency and dilated cardiomyopathy were fed diets that were either grain-free, legume-rich, or a combination of these factors. None of these diets were feeding trial tested using Association of American Feed Control Officials (AAFCO) procedures. Twenty-three of 24 dogs had significant improvement in their echocardiographic parameters and normalization of taurine concentrations following diet change and taurine supplementation. Nine of 11 dogs diagnosed with congestive heart failure (CHF) had resolution of their congestion at follow-up with five no longer requiring diuretic therapy and four tolerating diuretic dose reduction by >50%.Certain diets and diet characteristics were associated with the development of taurine deficiency. Taurine deficiency and dilated cardiomyopathy in golden retrievers is likely multifactorial, including a combination of dietary, metabolic, and genetic factors.}, number={12}, journal={PloS one}, author={Kaplan, Joanna L and Stern, Joshua A and Fascetti, Andrea J and Larsen, Jennifer A and Skolnik, Hannah and Peddle, Gordon D and Kienle, Richard D and Waxman, Andrew and Cocchiaro, Michael and Gunther-Harrington, Catherine T and et al.}, editor={Loor, Juan JEditor}, year={2018}, pages={e0209112} }
 @article{mansour_lucot_konopelski_dickinson_sturges_vernau_choi_stern_thomasy_döring_et al._2018, title={Whole genome variant association across 100 dogs identifies a frame shift mutation in DISHEVELLED 2 which contributes to Robinow-like syndrome in Bulldogs and related screw tail dog breeds}, volume={14}, url={https://europepmc.org/articles/PMC6303079}, DOI={10.1371/journal.pgen.1007850}, abstractNote={Domestic dog breeds exhibit remarkable morphological variations that result from centuries of artificial selection and breeding. Identifying the genetic changes that contribute to these variations could provide critical insights into the molecular basis of tissue and organismal morphogenesis. Bulldogs, French Bulldogs and Boston Terriers share many morphological and disease-predisposition traits, including brachycephalic skull morphology, widely set eyes and short stature. Unlike other brachycephalic dogs, these breeds also exhibit vertebral malformations that result in a truncated, kinked tail (screw tail). Whole genome sequencing of 100 dogs from 21 breeds identified 12.4 million bi-allelic variants that met inclusion criteria. Whole Genome Association of these variants with the breed defining phenotype of screw tail was performed using 10 cases and 84 controls and identified a frameshift mutation in the WNT pathway gene DISHEVELLED 2 (DVL2) (Chr5: 32195043_32195044del, p = 4.37 X 10−37) as the most strongly associated variant in the canine genome. This DVL2 variant was fixed in Bulldogs and French Bulldogs and had a high allele frequency (0.94) in Boston Terriers. The DVL2 variant segregated with thoracic and caudal vertebral column malformations in a recessive manner with incomplete and variable penetrance for thoracic vertebral malformations between different breeds. Importantly, analogous frameshift mutations in the human DVL1 and DVL3 genes cause Robinow syndrome, a congenital disorder characterized by similar craniofacial, limb and vertebral malformations. Analysis of the canine DVL2 variant protein showed that its ability to undergo WNT-induced phosphorylation is reduced, suggesting that altered WNT signaling may contribute to the Robinow-like syndrome in the screwtail breeds.}, number={12}, journal={PLoS genetics}, publisher={Public Library of Science (PLoS)}, author={Mansour, Tamer A and Lucot, Katherine and Konopelski, Sara E and Dickinson, Peter J and Sturges, Beverly K and Vernau, Karen L and Choi, Shannon and Stern, Joshua A and Thomasy, Sara M and Döring, Sophie and et al.}, editor={Leeb, TossoEditor}, year={2018}, pages={e1007850} }
 @article{ueda_stern_2017, title={A One Health Approach to Hypertrophic Cardiomyopathy.}, volume={9}, url={http://europepmc.org/abstract/med/28955182}, journal={The Yale journal of biology and medicine}, author={Ueda, Y and Stern, JA}, year={2017}, month={Sep} }
 @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{visser_sloan_stern_2017, title={Echocardiographic Assessment of Right Ventricular Size and Function in Cats With Hypertrophic Cardiomyopathy}, volume={31}, url={https://europepmc.org/articles/PMC5435046}, DOI={10.1111/jvim.14688}, abstractNote={Background Studies evaluating right ventricular ( RV ) structural and functional abnormalities in feline hypertrophic cardiomyopathy ( HCM ) are limited. Hypothesis Right ventricular structural and functional abnormalities are present in cats with HCM and are associated with clinical severity. Animals Eighty‐one client‐owned cats. Methods Retrospective 2‐dimensional (2D) echocardiographic study. Right atrial diameter ( RAD ), RV free wall thickness ( RVFW d), RV internal dimension ( RVID d), RV fractional area change ( FAC ), and tricuspid annular plane systolic excursion ( TAPSE ) were measured in control cats (n = 26), cats with subclinical HCM (subclinical HCM ; n = 31), and cats with HCM and congestive heart failure ( HCM + CHF ; n = 24). Results Right heart size ( RAD , RVFW d, and RVID d) and RV function ( FAC and TAPSE ) significantly (all P < .05) increased and decreased, respectively, in the HCM + CHF group compared with controls. In the subclinical HCM group, only RVFW d was significantly ( P < .05) higher than in controls. Compared with reference intervals derived from controls, 29% of cats with HCM had increased RVFW d. Increased left ventricular free wall thickness, increased RVID d and decreased TAPSE independently correlated with increased left atrial size. Cats with HCM and pleural effusion were significantly more likely to have increased RVFW d and had increased RAD and decreased TAPSE compared with cats without pleural effusion. Conclusions and Clinical Importance Right ventricular remodeling and dysfunction occur in some cats with HCM and may be associated with clinical severity. Our results support involvement of RV in the pathophysiology of HCM in some cats and support echocardiographic assessment of the RV in cats with HCM .}, number={3}, journal={Journal of veterinary internal medicine}, author={Visser, LC and Sloan, CQ and Stern, JA}, year={2017}, pages={668—677} }
 @article{ueda_gunther-harrington_cruzen_roberts_stern_2017, title={Echocardiographic Parameters of Clinically Normal Geriatric Rhesus Macaques (Macacamulatta).}, volume={7}, url={http://europepmc.org/abstract/med/28728613}, journal={Journal of the American Association for Laboratory Animal Science : JAALAS}, author={Ueda, Y and Gunther-Harrington, CT and Cruzen, CL and Roberts, JA and Stern, JA}, year={2017}, month={Jul} }
 @article{oyama_solter_thorn_stern_2017, title={Feasibility, safety, and tolerance of subcutaneous synthetic canine B-type natriuretic peptide (syncBNP) in healthy dogs and dogs with stage B1 mitral valve disease}, volume={19}, url={https://doi.org/10.1016/j.jvc.2017.02.003}, DOI={10.1016/j.jvc.2017.02.003}, number={3}, journal={Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology}, author={Oyama, MA and Solter, PF and Thorn, CL and Stern, JA}, year={2017}, pages={211—217} }
 @article{freeman_rush_stern_huggins_maron_2017, title={Feline Hypertrophic Cardiomyopathy: A Spontaneous Large Animal Model of Human HCM}, volume={8}, url={https://europepmc.org/articles/PMC5574284}, DOI={10.14740/cr578w}, abstractNote={Hypertrophic cardiomyopathy (HCM) is a common disease in pet cats, affecting 10-15% of the pet cat population. The similarity to human HCM, the rapid progression of disease, and the defined and readily determined endpoints of feline HCM make it an excellent natural model that is genotypically and phenotypically similar to human HCM. The Maine Coon and Ragdoll cats are particularly valuable models of HCM because of myosin binding protein-C mutations and even higher disease incidence compared to the overall feline population. The cat overcomes many of the limitations of rodent HCM models, and can provide enhanced translation of information from in vitro and induced small animal models to human clinical trials. Physicians and veterinarians working together in a collaborative and interdisciplinary approach can accelerate the discovery of more effective treatments for this and other cardiovascular diseases affecting human and veterinary patients. Cardiol Res. 2017;8(4):139-142 doi: https://doi.org/10.14740/cr578w}, number={4}, journal={Cardiology research}, author={Freeman, Lisa M and Rush, John E and Stern, Joshua A and Huggins, Gordon S and Maron, Martin S}, year={2017}, pages={139—142} }
 @article{zoller_guzman_summa_keller_silverman_stern_2017, title={Infundibular Pulmonic Stenosis in a Moluccan Cockatoo (Cacatua moluccensis)}, volume={31}, url={https://doi.org/10.1647/2015-126}, DOI={10.1647/2015-126}, abstractNote={A 31-year-old female Moluccan cockatoo (Cacatua moluccensis) was examined for intermittent foot clenching of 4 months' duration. Physical examination revealed feather-destructive behavior and clinical findings compatible with hypovitaminosis A. Neurologic examination was unremarkable. Results of radiographs, hematologic testing, plasma biochemical analyses, and measurement of lead and trace element blood concentrations were unremarkable, except for degenerative joint disease of several thoracic intervertebral joints and a low blood copper concentration. Increased dietary copper was recommended. After a 6-month period without clinical signs, the bird presented again for episodes of foot weakness. Radiographic review was suggestive of mild pulmonary trunk enlargement. Echocardiography revealed mild mitral and aortic regurgitation, dilation of the ascending aorta, and a dilated right ventricle with turbulent right ventricular outflow. An electrocardiogram revealed a sinus rhythm and normal-appearing complexes. Nonselective fluoroscopic angiography was performed 3 weeks later because of persistent episodes of foot clenching and weakness. Infundibular pulmonic stenosis, poststenotic dilation of the pulmonic trunk, and proximal main pulmonary arteries were identified, as well as a mild narrowing of the descending aorta compatible with aortic stenosis. The bird was discharged without medication but with dietary recommendations and experienced 2 clenching episodes in the days after the last visit. No recurrence of clinical signs has been reported over the 18-month follow-up period. To our knowledge, this is the first report of infundibular pulmonic stenosis in a bird. This case illustrates the application of basic and advanced diagnostic imaging modalities in evaluating cardiac disease in birds.}, number={1}, journal={Journal of avian medicine and surgery}, author={Zoller, Graham and Guzman, David Sanchez-Migallon and Summa, Noémie and Keller, Krista A and Silverman, Sarah J and Stern, Joshua A}, year={2017}, pages={53—61} }
 @article{mauler_gandolfi_reinero_dp o'brien_spooner_lyons_2017, title={Precision Medicine in Cats: Novel Niemann-Pick Type C1 Diagnosed by Whole-Genome Sequencing}, volume={31}, url={https://europepmc.org/articles/PMC5354023}, DOI={10.1111/jvim.14599}, abstractNote={State-of-the-art health care includes genome sequencing of the patient to identify genetic variants that contribute to either the cause of their malady or variants that can be targeted to improve treatment. The goal was to introduce state-of-the-art health care to cats using genomics and a precision medicine approach. To test the feasibility of a precision medicine approach in domestic cats, a single cat that presented to the University of Missouri, Veterinary Health Center with an undiagnosed neurologic disease was whole-genome sequenced. The DNA variants from the cat were compared to the DNA variant database produced by the 99 Lives Cat Genome Sequencing Consortium. Approximately 25× genomic coverage was produced for the cat. A predicted p.H441P missense mutation was identified in NPC1, the gene causing Niemann-Pick type C1 on cat chromosome D3.47456793 caused by an adenine-to-cytosine transversion, c.1322A>C. The cat was homozygous for the variant. The variant was not identified in any other 73 domestic and 9 wild felids in the sequence database or 190 additionally genotyped cats of various breeds. The successful effort suggested precision medicine is feasible for cats and other undiagnosed cats may benefit from a genomic analysis approach. The 99 Lives DNA variant database was sufficient but would benefit from additional cat sequences. Other cats with the mutation may be identified and could be introduced as a new biomedical model for NPC1. A genetic test could eliminate the disease variant from the population.}, number={2}, journal={Journal of veterinary internal medicine}, author={Mauler, DA and Gandolfi, B and Reinero, CR and DP O'Brien and Spooner, JL and Lyons, LA}, year={2017}, pages={539—544} }
 @article{a fas-ligand variant associated with autoimmune lymphoproliferative syndrome in cats._2016, url={https://doi.org/10.1007/s00335-016-9668-1}, DOI={10.1007/s00335-016-9668-1}, journal={Mammalian genome : official journal of the International Mammalian Genome Society}, year={2016}, month={Oct} }
 @article{stern_markova_ueda_kim_pascoe_evanchik_green_harris_2016, title={A Small Molecule Inhibitor of Sarcomere Contractility Acutely Relieves Left Ventricular Outflow Tract Obstruction in Feline Hypertrophic Cardiomyopathy}, volume={11}, url={https://europepmc.org/articles/PMC5156432}, DOI={10.1371/journal.pone.0168407}, abstractNote={Hypertrophic cardiomyopathy (HCM) is an inherited disease of the heart muscle characterized by otherwise unexplained thickening of the left ventricle. Left ventricular outflow tract (LVOT) obstruction is present in approximately two-thirds of patients and substantially increases the risk of disease complications. Invasive treatment with septal myectomy or alcohol septal ablation can improve symptoms and functional status, but currently available drugs for reducing obstruction have pleiotropic effects and variable therapeutic responses. New medical treatments with more targeted pharmacology are needed, but the lack of preclinical animal models for HCM with LVOT obstruction has limited their development. HCM is a common cause of heart failure in cats, and a subset exhibit systolic anterior motion of the mitral valve leading to LVOT obstruction. MYK-461 is a recently-described, mechanistically novel small molecule that acts at the sarcomere to specifically inhibit contractility that has been proposed as a treatment for HCM. Here, we use MYK-461 to test whether direct reduction in contractility is sufficient to relieve LVOT obstruction in feline HCM. We evaluated mixed-breed cats in a research colony derived from a Maine Coon/mixed-breed founder with naturally-occurring HCM. By echocardiography, we identified five cats that developed systolic anterior motion of the mitral valve and LVOT obstruction both at rest and under anesthesia when provoked with an adrenergic agonist. An IV MYK-461 infusion and echocardiography protocol was developed to serially assess contractility and LVOT gradient at multiple MYK-461 concentrations. Treatment with MYK-461 reduced contractility, eliminated systolic anterior motion of the mitral valve and relieved LVOT pressure gradients in an exposure-dependent manner. Our findings provide proof of principle that acute reduction in contractility with MYK-461 is sufficient to relieve LVOT obstruction. Further, these studies suggest that feline HCM will be a valuable translational model for the study of disease pathology, particularly LVOT obstruction.}, number={12}, journal={PloS one}, author={Stern, Joshua A and Markova, Svetlana and Ueda, Yu and Kim, Jae B and Pascoe, Peter J and Evanchik, Marc J and Green, Eric M and Harris, Samantha P}, year={2016}, pages={e0168407} }
 @article{haertel_stern_spinner_roberts_christe_2016, title={Antemortem Screening for Left Ventricular Hypertrophy in Rhesus Macaques (Macaca mulatta).}, url={http://europepmc.org/abstract/med/27538864}, journal={Comparative medicine}, author={Haertel, AJ and Stern, JA and Spinner, A and Roberts, JA and Christe, KL}, year={2016}, month={Jan} }
 @article{visser_im_johnson_stern_2016, title={Diagnostic Value of Right Pulmonary Artery Distensibility Index in Dogs with Pulmonary Hypertension: Comparison with Doppler Echocardiographic Estimates of Pulmonary Arterial Pressure}, volume={30}, url={https://europepmc.org/articles/PMC4913611}, DOI={10.1111/jvim.13911}, abstractNote={Background Noninvasive diagnosis of pulmonary hypertension ( PH ) primarily relies upon Doppler echocardiography of tricuspid regurgitation ( TR ). However, TR might be absent or difficult to measure. Hypothesis/Objectives To determine the diagnostic value of right pulmonary artery distensibility ( RPAD ) index for prediction of Doppler‐derived estimates of pulmonary artery ( PA ) pressure compared to other indices of PH in dogs. Animals Sixty‐nine client‐owned dogs with TR . Methods Prospective observational study. Dogs were allocated to groups according to TR pressure gradient ( TRPG ): TRPG <36 mmHg (control, n = 22), TRPG 36–50 (n = 16), TRPG 50–75 (n = 14) and TRPG >75 mmHg (n = 17). Right pulmonary artery distensibility index, acceleration time to peak PA flow ( AT ), AT : ejection time of PA flow ( AT : ET ) and main PA size: aorta size ( MPA :Ao) were calculated in each dog. Results Right pulmonary artery distensibility index demonstrated the strongest correlation ( r = −0.90; P < .0001) to TRPG followed by MPA :Ao ( r = 0.78; P < .0001), AT ( r = −0.69; P < .0001) and AT : ET ( r = −0.68; P < .0001). RPAD index possessed the most accurate cutoff (<29.5%; Sensitivity [Sn] 0.84, Specificity [Sp] 0.95) to predict TRPG >50 mmHg compared to AT (<53.9 ms; Sn 0.74, Sp 0.87), AT : ET (<0.30; Sn 0.61, Sp 0.97) and MPA :Ao (>1.04; Sn 0.94, Sp 0.74). All intra‐ and interobserver measurement variabilities exhibited coefficients of variation ≤13%. Conclusions and Clinical Importance Right pulmonary artery distensibility index is an accurate predictor of TRPG and should be particularly useful if TR is absent or difficult to measure.}, number={2}, journal={Journal of veterinary internal medicine}, author={Visser, LC and Im, MK and Johnson, LR and Stern, JA}, year={2016}, pages={543—552} }
 @article{im_stern_2016, title={ECG of the Month}, volume={248}, url={https://doi.org/10.2460/javma.248.5.497}, DOI={10.2460/javma.248.5.497}, number={5}, journal={Journal of the American Veterinary Medical Association}, author={Im, Minu and Stern, Joshua A}, year={2016}, pages={497—500} }
 @article{bélanger_visser_stern_2016, title={ECG of the Month}, volume={249}, url={https://doi.org/10.2460/javma.249.10.1138}, DOI={10.2460/javma.249.10.1138}, number={10}, journal={Journal of the American Veterinary Medical Association}, author={Bélanger, Catherine and Visser, Lance C and Stern, Joshua A}, year={2016}, pages={1138—1140} }
 @article{gunther-harrington_ontiveros_hodge_visser_stern_2016, title={Effects of 0.5% Timolol Maleate Ophthalmic Solution on Heart Rate and Selected Echocardiographic Indices in Apparently Healthy Cats}, volume={30}, url={https://europepmc.org/articles/PMC4913573}, DOI={10.1111/jvim.13931}, abstractNote={Echocardiographic assessment of diastolic function is challenging in cats, partially because of transmitral flow pattern fusion associated with high heart rates. With heart rate (HR) reduction, transmitral flow waveforms separate, allowing identification of diastolic dysfunction. Timolol, an ophthalmic, nonselective beta-blocker used in glaucoma is safe and transiently decreases HR in clinical trials.Administration of timolol ophthalmic solution decreases HR and facilitates echocardiographic assessment of diastolic function in cats without inducing clinically relevant adverse effects.Twenty-five apparently healthy cats.Electrocardiograms and echocardiograms including transmitral flow patterns were evaluated before and 20 minutes after ocular administration of 1 drop of timolol 0.5% solution. Twenty cats underwent treatment with timolol, and 5 different cats served as untreated controls to evaluate the effects of acclimation to the hospital environment on HR.Acclimation to the hospital had no effect on HR in control cats. After timolol administration, a significant median HR reduction of 25 bpm was observed (P < .0001). Timolol had no effect on E/A ratio in cats without E/A fusion (7/20, P = .44). Of the 13 cats with E and A waves that were fused before timolol application, separation of these waves was identified in 8 cats (62%) after timolol treatment. No bradyarrhythmias were noted after timolol administration, but 2 cats had first-degree atrioventricular block. Timolol resulted in resolution of dynamic outflow tract obstruction in 6 of 6 cats.Ocular administration of timolol safely decreases HR in cats and could facilitate assessment of diastolic function.}, number={3}, journal={Journal of veterinary internal medicine}, author={Gunther-Harrington, CT and Ontiveros, ES and Hodge, TE and Visser, LC and Stern, JA}, year={2016}, pages={733—740} }
 @article{visser_im_johnson_stern_2016, title={Letter to the Editor}, volume={30}, url={https://europepmc.org/articles/PMC5094509}, DOI={10.1111/jvim.14358}, abstractNote={We thank Drs. Kellihan and Chesler for their kind words and comments regarding our article “Diagnostic value of the right pulmonary artery distensibility index in dogs with pulmonary hypertension: Comparison with Doppler echocardiographic estimates of pulmonary arterial pressure” recently published in JVIM.1 In their letter, Drs. Kellihan and Chesler expressed concern regarding our use of the term “right pulmonary artery distensibility (RPAD) index” primarily because this index, as performed in our echocardiographic study, does not truly represent distensibility of the right pulmonary artery. As discussed, true pulmonary artery (PA) distensibility is determined by measuring the relative percent change in luminal area (cross-sectional area) of the artery (usually obtained via magnetic resonance imaging) for a given change in PA pressure (or pulse pressure – usually obtained invasively via right heart catheterization) during a cardiac cycle and is expressed as %/mmHg.2-4 We appreciate the desire of Drs. Kellihan and Chesler to standardize terms used in defining pulmonary hypertension (PH) and agree that terminology can be misleading. By definition, the RPAD index is dissimilar to and does not quantify true distensibility of the right PA. Instead, the RPAD index quantifies relative (or percent) diameter change in the PA throughout the cardiac cycle and can be conceptually thought of as a shortening fraction of the right PA derived via echocardiography. Our rationale for using the term RPAD index was primarily based on it previously being used in the clinical veterinary literature to describe relative changes in pulmonary artery diameter throughout the cardiac cycle and its associated changes with varying degrees of PH5, 6 and because it represents a noninvasive, readily obtainable, and easily understood echocardiographic measure.6 Drs. Kellihan and Chesler advocate use of the term “right pulmonary artery relative area change (RPA RAC)” rather than “RPAD index” and suggest this alternate term will accomplish the goal of more accurately describing the right PA measurement utilized in our study. We respectfully disagree and also find this proposed terminology to be misleading. In our study, we did not quantify the right PA cross-sectional area (or its relative change) but instead quantified the relative change in luminal diameter of the right PA throughout the cardiac cycle. Further, we recommend not deriving the cross-sectional area of an artery from a diameter measurement, as small errors in diameter (radius) measurement will be greatly magnified based on the formula: π × radius2. Lastly, we and others1, 6 found relative diameter change in the right PA (RPAD index) to be a practical, repeatable, and accurate predictor of invasive PA pressure and echocardiographically derived tricuspid regurgitation systolic pressure gradient in dogs with naturally occurring PH. In conclusion, we agree that the current terminology describing PA properties in dogs with PH might be misleading, particularly when considering measurements derived from advanced imaging techniques (eg, magnetic resonance imaging). However, we do not believe that RPA RAC is more appropriate than RPAD index. A more accurate term might be “right PA relative diameter change” rather than the currently used nomenclature. Despite disagreement in nomenclature, we maintain the clinical value of the RPAD index when echocardiographically screening dogs for PH and suggest continued use of this terminology due to it being consistently reported in this manner within the clinical veterinary literature.}, number={4}, journal={Journal of veterinary internal medicine}, author={Visser, LC and Im, MK and Johnson, LR and Stern, JA}, year={2016}, pages={926} }
 @article{li_stern_ho_tablin_harris_2016, title={Platelet Activation and Clopidogrel Effects on ADP-Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3}, volume={30}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/jvim.14568}, DOI={10.1111/jvim.14568}, abstractNote={BackgroundClopidogrel is commonly prescribed to cats with perceived increased risk of thromboembolic events, but little information exists regarding its antiplatelet effects.ObjectiveTo determine effects of clopidogrel on platelet responsiveness in cats with or without the A31P mutation in the MYBPC3 gene. A secondary aim was to characterize variability in feline platelet responses to clopidogrel.AnimalsFourteen healthy cats from a Maine Coon/outbred mixed Domestic cat colony: 8 cats homozygous for A31P mutation in the MYPBC3 gene and 6 wild‐type cats without the A31P mutation.MethodsEx vivo study. All cats received clopidogrel (18.75 mg PO q24h) for 14 days. Before and after clopidogrel treatment, adenosine diphosphate (ADP)‐induced P‐selectin expression was evaluated. ADP‐ and thrombin‐induced platelet aggregation was measured by optical aggregometry (OA). Platelet pVASP and ADP receptor response index (ARRI) were measured by Western blot analysis.ResultsPlatelet activation from cats with the A31P mutation was significantly (P = .0095) increased [35.55% (18.58–48.55) to 58.90% (24.85–69.90)], in response to ADP. Clopidogrel treatment attenuated ADP‐induced P‐selectin expression and platelet aggregation. ADP‐ and PGE1‐treated platelets had a similar level of pVASP as PGE1‐treated platelets after clopidogrel treatment. Clopidogrel administration resulted in significantly lower ARRI [24.13% (12.46–35.50) to 11.30% (−7.383 to 23.27)] (P = .017). Two of 13 cats were nonresponders based on OA and flow cytometry.Conclusion and Clinical ImportanceClopidogrel is effective at attenuating platelet activation and aggregation in some cats. Cats with A31P mutation had increased platelet activation relative to the variable response seen in wild‐type cats.}, number={5}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Li, R.H.L. and Stern, J.A. and Ho, V. and Tablin, F. and Harris, S.P.}, year={2016}, month={Sep}, pages={1619–1629} }
 @article{yamamoto_kent_wisner_johnson_stern_qi_fujita_boone_2016, title={Single-energy computed tomography-based pulmonary perfusion imaging: Proof-of-principle in a canine model}, volume={43}, url={https://europepmc.org/articles/PMC5438244}, DOI={10.1118/1.4953188}, abstractNote={Radiotherapy (RT) that selectively avoids irradiating highly functional lung regions may reduce pulmonary toxicity, which is substantial in lung cancer RT. Single-energy computed tomography (CT) pulmonary perfusion imaging has several advantages (e.g., higher resolution) over other modalities and has great potential for widespread clinical implementation, particularly in RT. The purpose of this study was to establish proof-of-principle for single-energy CT perfusion imaging.Single-energy CT perfusion imaging is based on the following: (1) acquisition of end-inspiratory breath-hold CT scans before and after intravenous injection of iodinated contrast agents, (2) deformable image registration (DIR) for spatial mapping of those two CT image data sets, and (3) subtraction of the precontrast image data set from the postcontrast image data set, yielding a map of regional Hounsfield unit (HU) enhancement, a surrogate for regional perfusion. In a protocol approved by the institutional animal care and use committee, the authors acquired CT scans in the prone position for a total of 14 anesthetized canines (seven canines with normal lungs and seven canines with diseased lungs). The elastix algorithm was used for DIR. The accuracy of DIR was evaluated based on the target registration error (TRE) of 50 anatomic pulmonary landmarks per subject for 10 randomly selected subjects as well as on singularities (i.e., regions where the displacement vector field is not bijective). Prior to perfusion computation, HUs of the precontrast end-inspiratory image were corrected for variation in the lung inflation level between the precontrast and postcontrast end-inspiratory CT scans, using a model built from two additional precontrast CT scans at end-expiration and midinspiration. The authors also assessed spatial heterogeneity and gravitationally directed gradients of regional perfusion for normal lung subjects and diseased lung subjects using a two-sample two-tailed t-test.The mean TRE (and standard deviation) was 0.6 ± 0.7 mm (smaller than the voxel dimension) for DIR between pre contrast and postcontrast end-inspiratory CT image data sets. No singularities were observed in the displacement vector fields. The mean HU enhancement (and standard deviation) was 37.3 ± 10.5 HU for normal lung subjects and 30.7 ± 13.5 HU for diseased lung subjects. Spatial heterogeneity of regional perfusion was found to be higher for diseased lung subjects than for normal lung subjects, i.e., a mean coefficient of variation of 2.06 vs 1.59 (p = 0.07). The average gravitationally directed gradient was strong and significant (R(2) = 0.99, p < 0.01) for normal lung dogs, whereas it was moderate and nonsignificant (R(2) = 0.61, p = 0.12) for diseased lung dogs.This canine study demonstrated the accuracy of DIR with subvoxel TREs on average, higher spatial heterogeneity of regional perfusion for diseased lung subjects than for normal lung subjects, and a strong gravitationally directed gradient for normal lung subjects, providing proof-of-principle for single-energy CT pulmonary perfusion imaging. Further studies such as comparison with other perfusion imaging modalities will be necessary to validate the physiological significance.}, number={7}, journal={Medical physics}, author={Yamamoto, Tokihiro and Kent, Michael S and Wisner, Erik R and Johnson, Lynelle R and Stern, Joshua A and Qi, Lihong and Fujita, Yukio and Boone, John M}, year={2016}, pages={3998} }
 @article{silverman_sanchez-migallon_stern_gustavsen_griffiths_2016, title={Standardization of the two-dimensional transcoelomic echocardiographic examination in the central bearded dragon (Pogona vitticeps).}, url={https://doi.org/10.1016/j.jvc.2015.10.011}, DOI={10.1016/j.jvc.2015.10.011}, journal={Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology}, author={Silverman, S and Sanchez-Migallon, Guzman D and Stern, Joshua and Gustavsen, Kate and Griffiths, Leigh}, year={2016}, month={Jan} }
 @article{dijk_bezold kooiker_mazzalupo_yang_kostyukova_mustacich_hoye_stern_kittleson_harris_2016, title={The A31P missense mutation in cardiac myosin binding protein C alters protein structure but does not cause haploinsufficiency}, volume={601}, url={https://europepmc.org/articles/PMC5843467}, DOI={10.1016/j.abb.2016.01.006}, journal={Archives of biochemistry and biophysics}, author={Dijk, Sabine J and Bezold Kooiker, Kristina and Mazzalupo, Stacy and Yang, Yuanzhang and Kostyukova, Alla S and Mustacich, Debbie J and Hoye, Elaine R and Stern, Joshua A and Kittleson, Mark D and Harris, Samantha P}, year={2016}, pages={133—140} }
 @article{gunther-harrington_michel_stern_2015, title={Acquired tricuspid valve stenosis due to intentionally redundant transvenous lead placement for VDD pacing in two small dogs}, volume={17}, url={https://doi.org/10.1016/j.jvc.2015.04.004}, DOI={10.1016/j.jvc.2015.04.004}, number={4}, journal={Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology}, author={Gunther-Harrington, Catherine T and Michel, Adam O and Stern, Joshua A}, year={2015}, pages={298—303} }
 @article{bozorgmanesh_magdesian_estell_stern_swain_griffiths_2016, title={Atrial Fibrillation in Eight New World Camelids}, volume={30}, url={https://europepmc.org/articles/PMC4913670}, DOI={10.1111/jvim.13798}, abstractNote={There is limited information on the incidence of clinical signs, concurrent illness and treatment options for atrial fibrillation (AF) in New World Camelids (NWC).Describe clinical signs and outcome of AF in NWC.Eight New World Camelids admitted with AF.A retrospective observational study of camelids diagnosed with AF based on characteristic findings on electrocardiogram (ECG).All animals had an irregularly irregular heart rhythm detected on physical examination and 4 cases had obtunded mentation on admission. Three camelids were diagnosed with AF secondary to oleander intoxication, 3 animals had underlying cardiovascular disease, 1 was diagnosed with lone AF and 1 had AF diagnosed on examination for a urethral obstruction. Five of eight animals survived to discharge and nonsurvivors consisted of animals which died or were euthanized as a result of cardiovascular disease (2/8) or extra-cardiac disease unrelated to the AF (1/8).Atrial fibrillation occurs in NWC in association with cardiovascular disease, extra-cardiac disease or as lone AF. Amiodarone and transthoracic cardioversion were attempted in one llama with lone AF, but were unsuccessful. Atrial fibrillation was recorded in 0.1% of admissions.}, number={1}, journal={Journal of veterinary internal medicine}, author={Bozorgmanesh, R and Magdesian, KG and Estell, KE and Stern, JA and Swain, EA and Griffiths, LG}, year={2016}, pages={335—338} }
 @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} }
 @article{kittleson_stern_brown_2015, title={Predicting development of subaortic stenosis in dogs}, volume={246}, url={https://doi.org/10.2460/javma.246.10.1058}, DOI={10.2460/javma.246.10.1058}, number={10}, journal={Journal of the American Veterinary Medical Association}, author={Kittleson, Mark D and Stern, Joshua A and Brown, Donald J}, year={2015}, pages={1058} }
 @article{stern_hsue_song_ontiveros_luis fuentes_stepien_2015, title={Severity of Mitral Valve Degeneration Is Associated with Chromosome 15 Loci in Whippet Dogs}, volume={10}, url={https://europepmc.org/articles/PMC4624976}, DOI={10.1371/journal.pone.0141234}, abstractNote={Mitral valve degeneration (MVD) is the most common form of heart disease in dogs, frequently leading to left-sided congestive heart failure and cardiac mortality. Although breed-specific disease characteristics and overrepresentation point towards a genetic origin for MVD, a causative mutation and complete molecular pathogenesis are unknown. Whippet dogs are overrepresented in incidence of MVD, suggesting an inherited component in this breed. Expressivity of this condition is variable with some dogs showing evidence of more severe disease at earlier ages than other dogs. This phenomenon makes a traditional case versus control genetic study prone to phenotyping error. This study sought to avoid these common pitfalls by identifying genetic loci associated with severity of MVD in Whippets through a genome-wide association study (GWAS). 138 Whippet dogs were characterized for MVD by echocardiographic examination and a novel disease severity score was developed and adjusted for age in each subject. Single nucleotide polymorphism (SNP) genotype data (170k Illumina CanineHD SnpChip) was obtained for DNA isolated from blood of each study subject. Continuous variable genome wide association was performed after correction for population stratification by efficient mixed model association expedited (EMMAX) in 130 dogs. A genome wide significant association was identified on chromosome 15 (peak locus 57,770,326; Padj = 0.049) and secondary loci of suggestive association were identified on chromosome 2 (peak locus 37,628,875; Padj = 0.079). Positional candidate genes were identified within the primary and secondary loci including follistatin-related protein 5 precursor (FSTL5) and Rho GTPase-activating protein 26 (ARHGAP26). These results support the hypothesis that severity of MVD in whippets has a genetic basis and warrants further study by either candidate gene sequencing or next-generation techniques.}, number={10}, journal={PloS one}, author={Stern, Joshua A and Hsue, Weihow and Song, Kun-Ho and Ontiveros, Eric S and Luis Fuentes, Virginia and Stepien, Rebecca L}, year={2015}, pages={e0141234} }
 @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{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={{"Label"=>"OBJECTIVES", "NlmCategory"=>"OBJECTIVE"} 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). {"Label"=>"ANIMALS", "NlmCategory"=>"METHODS"} Sixty-four Ragdoll cats. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} 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. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} 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. {"Label"=>"CONCLUSIONS", "NlmCategory"=>"CONCLUSIONS"} 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{costa_lahmers_barry_stanton_stern_2014, title={Fungal pericarditis and endocarditis secondary to porcupine quill migration in a dog}, volume={16}, url={https://doi.org/10.1016/j.jvc.2014.09.003}, DOI={10.1016/j.jvc.2014.09.003}, number={4}, journal={Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology}, author={Costa, Ana and Lahmers, Sunshine and Barry, Sabrina L and Stanton, James and Stern, Joshua A}, year={2014}, pages={283—290} }
 @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} }
 @article{reina doreste_stern_lahmers_2013, title={ECG of the month. Multiple episodes of collapse in a cat}, volume={242}, url={https://doi.org/10.2460/javma.242.7.926}, DOI={10.2460/javma.242.7.926}, number={7}, journal={Journal of the American Veterinary Medical Association}, author={Reina Doreste, Yamir and Stern, Joshua A and Lahmers, Sunshine M}, year={2013}, pages={926—928} }
 @article{stern_hinchcliff_constable_2013, title={Effect of body position on electrocardiographic recordings in dogs}, volume={91}, url={https://doi.org/10.1111/avj.12076}, DOI={10.1111/avj.12076}, abstractNote={Objective To determine whether body position (standing vs right lateral recumbency) altered the quality of the electrocardiogram ( ECG ) and value of ECG variables in dogs when the ECG was recorded using American Heart Association guidelines for frequency response. Design Crossover study using a convenience sample. Methods ECGs were recorded twice in 65 sled dogs in random order with each dog standing or placed in right lateral recumbency. Lead II and three semi‐orthogonal leads ( I , aVF , and V 10 ) were recorded and muscle tremor artefact was assessed. Results Lead II ECGs obtained from dogs in right lateral recumbency had less muscle tremor artefact and consequently a shorter QRS duration than ECGs obtained with the dogs standing. The P , Q , R and S wave amplitudes differed in selected leads and the mean electrical axis was shifted 20° to the right when dogs were in right lateral recumbency. Conclusions Right lateral recumbency improves the quality of ECG recording in dogs by decreasing muscle tremor artefact, alters the amplitude of P , R and S waves in specific leads and results in a rightward shift in the mean electrical axis, relative to standing.}, number={7}, journal={Australian veterinary journal}, publisher={Wiley}, author={Stern, JA and Hinchcliff, KW and Constable, PD}, year={2013}, pages={281—286} }
 @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{stern_tou_barker_hill_lodge_mathews_keene_2013, title={Hybrid cutting balloon dilatation for treatment of cor triatriatum sinister in a cat}, volume={15}, ISSN={["1875-0834"]}, url={https://doi.org/10.1016/j.jvc.2013.03.001}, DOI={10.1016/j.jvc.2013.03.001}, abstractNote={A hybrid surgical approach and balloon dilatation were performed successfully in a cat with cor triatriatum sinister and clinical signs of congestive heart failure. Left lateral thoracotomy was used to access the heart and cutting balloon followed by standard balloon dilatation were utilized to dilate the perforation in the anomalous left atrial membrane. Clinical signs resolved completely after dilation of the anomalous left atrial membrane. Based upon the outcome of this case, balloon dilatation appears to be a viable treatment option for cats affected with cor triatriatum sinister.}, number={3}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Stern, Joshua A. and Tou, Sandra P. and Barker, Piers C. A. and Hill, Kevin D. and Lodge, Andrew J. and Mathews, Kyle G. and Keene, Bruce W.}, year={2013}, month={Sep}, pages={205–210} }
 @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{stern_tobias_keene_2012, title={Complete atrioventricular block secondary to cardiac lymphoma in a dog}, volume={14}, ISSN={1760-2734}, url={http://dx.doi.org/10.1016/j.jvc.2012.04.007}, DOI={10.1016/j.jvc.2012.04.007}, abstractNote={Third degree atrioventricular (AV) block was observed in a patient with a roughly spherical mass measuring approximately 1 × 1 × 1 cm, visible in the basilar portion of the interventricular septum on 2-dimensional transthoracic echocardiographic examination. The patient had a brief history of lethargy and episodic collapse, and the owner elected to euthanize the dog after the mass lesion was discovered. Necropsy revealed multiple masses within the interventricular septum, ventricular free walls and atrial myocardium. The final diagnosis was large cell (T-cell) lymphosarcoma.}, number={4}, journal={Journal of Veterinary Cardiology}, publisher={Elsevier BV}, author={Stern, Joshua A. and Tobias, Jeremy R. and Keene, Bruce W.}, year={2012}, month={Dec}, pages={537–539} }
 @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{stern_doreste_barnett_lahmers_baumwart_seino_bonagura_2012, title={Resolution of sustained narrow complex ventricular tachycardia and tachycardia-induced cardiomyopathy in a Quarter Horse following quinidine therapy.}, volume={9}, url={http://europepmc.org/abstract/med/22841902}, DOI={10.1016/j.jvc.2012.05.004}, abstractNote={Sustained narrow-QRS tachycardia of three months duration and left ventricular systolic dysfunction were identified in a fifteen-year-old Quarter Horse. No underlying cause for the tachyarrhythmia was found and no predisposing structural cardiac lesions were evident by echocardiography. Intravenous diltiazem and lidocaine were administered without achieving successful conversion of the arrhythmia. Oral quinidine therapy converted the tachyarrhythmia to sinus rhythm. Ventricular systolic dysfunction and chamber dilatation subsequently resolved. As with other species, echocardiographic features of dilated cardiomyopathy can be tachycardia-induced and may resolve following successful control of heart rate and rhythm.}, number={3}, journal={Journal of veterinary cardiology : the official journal of the European Society of Veterinary Cardiology}, author={Stern, JA and Doreste, YR and Barnett, S and Lahmers, SM and Baumwart, RD and Seino, KK and Bonagura, JD}, year={2012}, month={Jul}, pages={445—451} }
 @article{stern_chew_schissler_green_2011, title={Cutaneous and systemic blastomycosis, hypercalcemia, and excess synthesis of calcitriol in a domestic shorthair cat}, volume={47}, url={https://doi.org/10.5326/JAAHA-MS-5566}, DOI={10.5326/jaaha-ms-5566}, abstractNote={A 9 yr old domestic shorthair cat was diagnosed with cutaneous and pulmonic blastomycosis. Severe persistent ionized hypercalcemia and excess circulating concentration of calcitriol were documented in association with blastomycosis. Ionized hypercalcemia resolved when the granulomatous lesions of blastomycosis resolved and the calcitriol levels decreased.}, number={6}, journal={Journal of the American Animal Hospital Association}, author={Stern, Joshua A and Chew, Dennis J and Schissler, Jennifer R and Green, Eric M}, year={2011}, pages={e116—20} }
 @article{johns_stern_nelson_2011, title={ECG of the month. Hyperkalemia}, volume={238}, url={https://avmajournals.avma.org/downloadpdf/journals/javma/238/8/javma.238.8.982.pdf}, DOI={10.2460/javma.238.8.982}, number={8}, journal={Journal of the American Veterinary Medical Association}, author={Johns, Sara M and Stern, Joshua A and Nelson, O Lynne}, year={2011}, pages={982—984} }
 @article{schober_hart_stern_li_samii_zekas_scansen_bonagura_2011, title={Effects of treatment on respiratory rate, serum natriuretic peptide concentration, and Doppler echocardiographic indices of left ventricular filling pressure in dogs with congestive heart failure secondary to degenerative mitral valve disease and dilated cardiomyopathy}, volume={239}, url={https://doi.org/10.2460/javma.239.4.468}, DOI={10.2460/javma.239.4.468}, abstractNote={Abstract
Objective—To evaluate the effects of treatment on respiratory rate, serum natriuretic peptide concentrations, and Doppler echocardiographic indices of left ventricular filling pressure in dogs with congestive heart failure (CHF) secondary to degenerative mitral valve disease (MVD) and dilated cardiomyopathy (DCM).
Design—Prospective cohort study.
Animals—63 client-owned dogs.
Procedures—Physical examination, thoracic radiography, analysis of natriuretic peptide concentrations, and Doppler echocardiography were performed twice, at baseline (examination 1) and 5 to 14 days later (examination 2). Home monitoring of respiratory rate was performed by the owners between examinations.
Results—In dogs with MVD, resolution of CHF was associated with a decrease in respiratory rate, serum N-terminal probrain natriuretic peptide (NT-proBNP) concentration, and diastolic functional class and an increase of the ratio of peak velocity of early diastolic transmitral flow to peak velocity of early diastolic lateral mitral annulus motion (E:Ea Lat). In dogs with DCM, resolution of CHF was associated with a decrease in respiratory rate and serum NT-proBNP concentration and significant changes in 7 Doppler echocardiographic variables, including a decrease of E:Ea Lat and the ratio of peak velocity of early diastolic transmitral flow to isovolumic relaxation time. Only respiratory rate predicted the presence of CHF at examination 2 with high accuracy.
Conclusions and Clinical Relevance—Resolution of CHF was associated with predictable changes in respiratory rate, serum NT-proBNP concentration, and selected Doppler echocardiographic variables in dogs with DCM and MVD. Home monitoring of respiratory rate was simple and was the most useful in the assessment of successful treatment of CHF.}, number={4}, journal={Journal of the American Veterinary Medical Association}, author={Schober, Karsten E and Hart, Taye M and Stern, Joshua A and Li, Xiaobai and Samii, Valerie F and Zekas, Lisa J and Scansen, Brian A and Bonagura, John D}, year={2011}, pages={468—479} }
 @article{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{schober_hart_stern_li_samii_zekas_scansen_bonagura_2010, title={Detection of congestive heart failure in dogs by Doppler echocardiography}, volume={24}, url={http://apt.allenpress.com/aptonline/?request=get-document&issn=0891-6640&volume=024&issue=06&page=1358}, DOI={10.1111/j.1939-1676.2010.0592.x}, abstractNote={BACKGROUND
Echocardiographic prediction of congestive heart failure (CHF) in dogs has not been prospectively evaluated.


HYPOTHESIS
CHF can be predicted by Doppler echocardiographic (DE) variables of left ventricular (LV) filling in dogs with degenerative mitral valve disease (MVD) and dilated cardiomyopathy (DCM).


ANIMALS
Sixty-three client-owned dogs.


METHODS
Prospective clinical cohort study. Physical examination, thoracic radiography, analysis of natriuretic peptides, and transthoracic echocardiography were performed. Diagnosis of CHF was based upon clinical and radiographic findings. Presence or absence of CHF was predicted using receiver-operating characteristic (ROC) curve, multivariate logistic and stepwise regression, and best subsets analyses.


RESULTS
Presence of CHF secondary to MVD or DCM could best be predicted by E:isovolumic relaxation time (IVRT) (area under the ROC curve [AUC]=0.97, P<.001), respiration rate (AUC=0.94, P<.001), Diastolic Functional Class (AUC=0.93, P<.001), and a combination of Diastolic Functional Class, IVRT, and respiration rate (R2=0.80, P<.001) or Diastolic Functional Class (AUC=1.00, P<.001), respiration rate (AUC=1.00, P<.001), and E:IVRT (AUC=0.99, P<.001), and a combination of Diastolic Functional Class and E:IVRT (R2=0.94, P<.001), respectively, whereas other variables including N-terminal pro-brain natriuretic peptide, E:Ea, and E:Vp were less useful.


CONCLUSION AND CLINICAL IMPORTANCE
Various DE variables can be used to predict CHF in dogs with MVD and DCM. Determination of the clinical benefit of such variables in initiating, modulating, and assessing success of treatments for CHF needs further study.}, number={6}, journal={Journal of veterinary internal medicine}, author={Schober, KE and Hart, TM and Stern, JA and Li, X and Samii, VF and Zekas, LJ and Scansen, BA and Bonagura, JD}, year={2010}, pages={1358—1368} }
 @article{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={{"Label"=>"OBJECTIVE", "NlmCategory"=>"OBJECTIVE"} To examine the presence and effect of calstabin2-deficiency in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC). {"Label"=>"ANIMALS", "NlmCategory"=>"METHODS"} Thirteen Boxer dogs with ARVC. {"Label"=>"MATERIALS AND METHODS", "NlmCategory"=>"METHODS"} Tissue samples were collected for histopathology, oligonucleotide microarray, PCR, immunoelectrophoresis, ryanodine channel immunoprecipitation and single-channel recordings, and calstabin2 DNA sequencing. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} 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 Ca(2+) leak. PCR-based sequencing of the promoter, exonic and splice site regions of the canine calstabin2 gene did not identify any causative mutations. {"Label"=>"CONCLUSIONS", "NlmCategory"=>"CONCLUSIONS"} Calstabin2 deficiency is a potential mechanism of Ca(2+) 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{schober_stern_dacunha_pedraza-toscano_shemanski_hamlin_2008, title={Estimation of left ventricular filling pressure by Doppler echocardiography in dogs with pacing-induced heart failure}, volume={22}, url={http://apt.allenpress.com/aptonline/?request=get-document&issn=0891-6640&volume=022&issue=03&page=0578}, DOI={10.1111/j.1939-1676.2008.0099.x}, abstractNote={Background: Congestive heart failure (CHF) is a common clinical syndrome characterized by elevated filling pressure. Hypothesis: Doppler echocardiographic (DE) variables of left ventricular (LV) filling can predict a decline of LV end‐diastolic pressure (LVEDP) induced by acute preload reduction in dogs with compensated CHF. Animals: Five male hound dogs. Methods: Dogs previously instrumented with a transvenous cardiac pacemaker and a LV pressure gauge were paced at 160–180 bpm to induce mild CHF characterized by LVEDP > 20 mmHg. LVEDP and 9 DE variables of LV filling derived from diastolic time intervals, transmitral and pulmonary venous flow, and tissue Doppler imaging were measured simultaneously at baseline and 30, 60, 120, and 240 minutes after furosemide (4 mg/kg, IV) or placebo (0.9% saline, IV). Repeated measures analysis of variance and correlation analysis were used to determine the association between the decline of LVEDP after furosemide and DE measures of LV filling pressure (LVFP). Results: Furosemide but not placebo decreased LVEDP ( P < .001). The ratio of early transmitral flow velocity to LV isovolumic relaxation time (E : IVRT) predicted LVEDP best ( R 2 = .50; P < .001). Correlations were also found between LVEDP and IVRT, E, ratio between E and late diastolic transmitral flow velocity (E : A), and early diastolic velocity of the mitral annulus (Ea). The ratio of E to Ea (E : Ea) was not useful in the prediction of LVEDP in this model. Conclusion and Clinical Importance: E : IVRT can be used to predict LVFP in dogs with mild left‐sided CHF induced by rapid pacing.}, number={3}, journal={Journal of veterinary internal medicine}, author={Schober, KE and Stern, JA and DaCunha, D N Q T and Pedraza-Toscano, AM and Shemanski, D and Hamlin, RL}, year={2008}, pages={578—585} }
 @article{schober_bonagura_scansen_stern_ponzio_2008, title={Estimation of left ventricular filling pressure by use of Doppler echocardiography in healthy anesthetized dogs subjected to acute volume loading}, volume={69}, url={https://avmajournals.avma.org/downloadpdf/journals/ajvr/69/8/ajvr.69.8.1034.pdf}, DOI={10.2460/ajvr.69.8.1034}, abstractNote={Abstract
Objective—To identify Doppler echocardiographic (DE) variables that correlate with left ventricular filling pressure (LVFP).
Animals—7 healthy dogs (1 to 3 years old).
Procedures—Dogs were anesthetized and instrumented to measure left atrial pressure (LAP), left ventricular pressures, and cardiac output. Nine DE variables of LVFP derived from diastolic time intervals, transmitral and pulmonary venous flow, and tissue Doppler images were measured over a range of hemodynamic states induced by volume loading and right atrial pacing. Associations between simultaneous invasive measures of LVFP and DE measures of LVFP were determined by use of regression analysis. Receiver operating characteristic analysis was used to predict increases in mean LAP on the basis of DE variables.
Results—Mean LAP was correlated with several DE variables: the ratio between peak velocity during early diastolic transmitral flow and left ventricular isovolumic relaxation time (peak E:IVRT) during sinus rhythm and during right atrial pacing, IVRT, the ratio between late diastolic transmitral flow velocity and pulmonary venous flow duration, and the interval between onset of early diastolic mitral annulus motion and onset of early diastolic transmitral flow. Cutoff values of 2.20 and 2.17, for peak E:IVRT in dogs with sinus rhythm and atrial pacing predicted increases in mean LAP (≥ 15 mm Hg) with sensitivities of 90% and 100% and specificities of 92% and 100%, respectively.
Conclusions and Clinical Relevance—Doppler echocardiography can be used to predict an increase in LVFP in healthy anesthetized dogs subjected to volume loading.}, number={8}, journal={American journal of veterinary research}, author={Schober, Karsten E and Bonagura, John D and Scansen, Brian A and Stern, Joshua A and Ponzio, Nicole M}, year={2008}, pages={1034—1049} }
 @article{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{schober_maerz_ludewig_stern_2007, title={Diagnostic accuracy of electrocardiography and thoracic radiography in the assessment of left atrial size in cats: comparison with transthoracic 2-dimensional echocardiography.}, url={https://doi.org/10.1892/0891-6640(2007)21[709:daoeat]2.0.co;2}, DOI={10.1111/j.1939-1676.2007.tb03012.x}, abstractNote={Background : Left atrial (LA) enlargement (LAE) is a morphologic expression of the severity and chronicity of left ventricular (LV) diastolic dysfunction, volume overload, and increased atrial pressure and has diagnostic, therapeutic, and prognostic importance in cats. The noninvasive gold standard for assessing LA size is 2‐dimensional echocardiography (2DE). Hypothesis : ECG and thoracic radiography may be used to predict LAE in cats. Animals : Twenty‐one healthy control cats and 31 cats with cardiomyopathy were prospectively studied. Methods : 2DE studies, including determination of the maximum LA dimension (LAD) and area (LAA), were performed prospectively in all cats and compared to the assessment of LA size based on thoracic radiography and indices obtained from a 6‐lead ECG. Results obtained from healthy cats were used to generate discrimination limits suggestive of LAE as defined by LAD >1.57 cm and LAA >2.75 cm 2 . Results : In cats with LAE, P wave duration and PR interval were prolonged and radiographic LA vertebral heart size (LA‐VHS) was increased ( P < .05). P wave‐related indices had low sensitivity (Se; range, 0.12 to 0.60) but high specificity (Sp; range, 0.81 to 1.00) for the prediction of LAE. Radiographic indices had low Se (range, 0.28 to 0.72) and high Sp (range, 0.74 to 0.95) for the prediction of LAE. Correlation analyses identified correlations between LAA and P wave duration ( r = 0.47, P = .003) and LAD and LA‐VHS ( r = 0.70, P < .001). Conclusion and Clinical Importance : ECG and thoracic radiography are reasonably specific but less sensitive predictors of LAE in cats.}, journal={Journal of veterinary internal medicine}, author={Schober, KE and Maerz, I and Ludewig, E and Stern, JA}, year={2007}, month={Jul} }