A single codon insertion in PICALM is associated with development of familial subvalvular aortic stenosis in Newfoundland dogs

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

Evaluation of point‐of‐care thoracic ultrasound and NT‐proBNP for the diagnosis of congestive heart failure in cats with respiratory distress

Background The diagnosis of congestive heart failure (CHF) in cats is challenging. Point‐of‐care (POC) thoracic ultrasound and NT‐proBNP testing are emerging tools that may aid in diagnosis. Hypothesis/Objectives To assess the diagnostic accuracy of POC lung ultrasound (LUS), focused cardiac ultrasound (FCU), and NT‐proBNP in predicting a final diagnosis of CHF. Animals Fifty‐one cats in respiratory distress. Methods Blood NT‐proBNP, LUS, and FCU evaluating left atrial (LA) size and presence of pericardial effusion (PCEFF) were performed in all cats. Lung ultrasound findings including pleural effusion (PLEFF), number of B‐lines, and sub‐pleural abnormalities were noted. Medical records were evaluated for final diagnosis. Results Thirty‐three of 51 (65%) cats were diagnosed with CHF. Lung ultrasound and blood NT‐proBNP were significant predictors of CHF in a multivariate model. The LUS criterion that maximized accuracy for CHF diagnosis was presence of \u3e1 site strongly positive for B‐lines (\u3e3 B‐lines per site), resulting in sensitivity of 78.8%, specificity of 83.3%, and area under the curve (AUC) of 0.833. Subjective LA enlargement was 97.0% sensitive and 100% specific for CHF (AUC 0.985). Presence of PCEFF also was 100% specific, but only 60.6% sensitive, for CHF (AUC 0.803). A positive blood NT‐proBNP test was 93.9% sensitive and 72.2% specific for the diagnosis of CHF (AUC 0.831). Conclusions and Clinical Importance Point‐of‐care diagnostic techniques of LUS, FCU, and NT‐proBNP are useful to diagnose CHF in cats with respiratory distress

Angiotensin-converting enzyme activity and inhibition in dogs with cardiac disease and an angiotensin-converting enzyme polymorphism

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

ECG of the month: Multiple episodes of collapse in a cat

No abstract available

Polymorphisms in the canine and feline renin-angiotensin-aldosterone system genes

No abstract available

Evaluation of point‐of‐care thoracic ultrasound and NT‐proBNP for the diagnosis of congestive heart failure in cats with respiratory distress

Background The diagnosis of congestive heart failure (CHF) in cats is challenging. Point‐of‐care (POC) thoracic ultrasound and NT‐proBNP testing are emerging tools that may aid in diagnosis. Hypothesis/Objectives To assess the diagnostic accuracy of POC lung ultrasound (LUS), focused cardiac ultrasound (FCU), and NT‐proBNP in predicting a final diagnosis of CHF. Animals Fifty‐one cats in respiratory distress. Methods Blood NT‐proBNP, LUS, and FCU evaluating left atrial (LA) size and presence of pericardial effusion (PCEFF) were performed in all cats. Lung ultrasound findings including pleural effusion (PLEFF), number of B‐lines, and sub‐pleural abnormalities were noted. Medical records were evaluated for final diagnosis. Results Thirty‐three of 51 (65%) cats were diagnosed with CHF. Lung ultrasound and blood NT‐proBNP were significant predictors of CHF in a multivariate model. The LUS criterion that maximized accuracy for CHF diagnosis was presence of >1 site strongly positive for B‐lines (>3 B‐lines per site), resulting in sensitivity of 78.8%, specificity of 83.3%, and area under the curve (AUC) of 0.833. Subjective LA enlargement was 97.0% sensitive and 100% specific for CHF (AUC 0.985). Presence of PCEFF also was 100% specific, but only 60.6% sensitive, for CHF (AUC 0.803). A positive blood NT‐proBNP test was 93.9% sensitive and 72.2% specific for the diagnosis of CHF (AUC 0.831). Conclusions and Clinical Importance Point‐of‐care diagnostic techniques of LUS, FCU, and NT‐proBNP are useful to diagnose CHF in cats with respiratory distress.This article is published as Ward, Jessica L., Gregory R. Lisciandro, Wendy A. Ware, Austin K. Viall, Brent D. Aona, Kari A. Kurtz, Yamir Reina‐Doreste, and Teresa C. DeFrancesco. "Evaluation of point‐of‐care thoracic ultrasound and NT‐proBNP for the diagnosis of congestive heart failure in cats with respiratory distress." Journal of Veterinary Internal Medicine 32, no. 5 (2018): 1530-1540. DOI: 10.1111/jvim.15246. Posted with permission.</p

Resolution of sustained narrow complex ventricular tachycardia and tachycardia-induced cardiomyopathy in a Quarter Horse following quinidine therapy

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

Impact of the canine double-deletion β1 adrenoreceptor polymorphisms on protein structure and heart rate response to atenolol, a β1-selective β-blocker

Objective: [beta]-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 [beta]-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

A single codon insertion in PICALM is associated with development of familial subvalvular aortic stenosis in Newfoundland dogs.

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

Case-control study of the effects of pimobendan on survival time in cats with hypertrophic cardiomyopathy and congestive heart failure

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