Use of whole genome analysis to identify shared genomic variants across breeds in canine mitral valve disease.

Familial mitral valve prolapse in human beings has been associated with several genetic variants; however, in most cases, a known variant has not been identified. Dogs also have a naturally occurring form of familial mitral valve disease (MMVD) with similarities to the human disease. A shared genetic background and clinical phenotype of this disease in some dog breeds has indicated that the disease may share a common genetic cause. We evaluated DNA from 50 affected dogs from five different dog breeds in a whole genome sequencing approach to identify shared variants across and within breeds that could be associated with MMVD. No single causative genetic mutation was found from the 50 dogs with MMVD. Ten variants were identified in 37/50 dogs around and within the MED13L gene. These variants were no longer associated with MMVD when evaluated with a larger cohort including both affected and unaffected dogs. No high/moderate impact variants were identified in 10/10 miniature poodles, one was identified in 10/10 Yorkshire Terriers and 10/10 dachshunds, respectively, 14 were identified in 10/10 Miniature schnauzers, and 19 in 10/10 CKCS. Only one of these could be associated with the cardiac valve (Chr12:36801705, COL12A1; CKCS) but when evaluated in an additional 100 affected CKCS the variant was only identified in 84/100 affected dogs, perhaps indicating genetic heterogeneity in this disease. Our findings indicate that development of MMVD in the dog may be related to a combination of genetic and environmental factors that impact specific molecular pathways rather than a single shared genetic variant across or within breeds.

A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death.

The dog provides a large animal model of familial dilated cardiomyopathy for the study of important aspects of this common familial cardiovascular disease. We have previously demonstrated a form of canine dilated cardiomyopathy in the Doberman pinscher breed that is inherited as an autosomal dominant trait and is associated with a splice site variant in the pyruvate dehydrogenase kinase 4 (PDK4) gene, however, genetic heterogeneity exists in this species as well and not all affected dogs have the PDK4 variant. Whole genome sequencing of a family of Doberman pinchers with dilated cardiomyopathy and sudden cardiac death without the PDK4 variant was performed. A pathologic missense variant in the titin gene located in an immunoglobulin-like domain in the I-band spanning region of the molecule was identified and was highly associated with the disease (p < 0.0001). We demonstrate here the identification of a variant in the titin gene highly associated with the disease in this spontaneous canine model of dilated cardiomyopathy. This large animal model of familial dilated cardiomyopathy shares many similarities with the human disease including mode of inheritance, clinical presentation, genetic heterogeneity and a pathologic variant in the titin gene. The dog is an excellent model to improve our understanding of the genotypic phenotypic relationships, penetrance, expression and the pathophysiology of variants in the titin gene.

Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease.

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.

Impact of the canine double-deletion ß1 adrenoreceptor polymorphisms on protein structure and heart rate response to atenolol, a ß1-selective ß-blocker.

OBJECTIVE: ß-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 ß-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 valentine-shaped cardiac silhouette in feline thoracic radiographs is primarily due to left atrial enlargement.

Conflicting information has been published regarding the cause of a valentine-shaped cardiac silhouette in dorsoventral or ventrodorsal thoracic radiographs in cats. The purpose of this retrospective, cross-sectional study was to test the hypothesis that the valentine shape is primarily due to left atrial enlargement. Images for cats with a radiographic valentine-shaped cardiac silhouette and full echocardiography examination were retrieved and independently reviewed. A subjective scoring system was used to record severity of radiographic valentine shape. Subjective radiographic evidence of left atrial enlargement in a radiographic lateral projection and a final diagnosis based on medical records were also recorded. A total of 81 cats met inclusion criteria. There was a strong positive correlation (P < 0.001) between echocardiographic left atrial size and severity of radiographic valentine shape. There was no effect of echocardiographic right atrial size on the severity of valentine shape, except when concurrent with severe left atrial enlargement. In this situation, right atrial enlargement increased the likelihood of observing a severe valentine shape. There was no effect of right atrial enlargement on the shape of the cardiac silhouette when left atrial enlargement was absent or only mild to moderate. There was no correlation between the category of final diagnosis of cardiac disease and the severity of valentine shape. Findings from this study supported the hypothesis that a valentine-shaped cardiac silhouette in radiographs is due primarily to left atrial enlargement in cats, with right atrial enlargement only impacting the shape if concurrent with severe left atrial enlargement.

Outcomes and complications associated with epicardial pacemakers in 28 dogs and 5 cats.

OBJECTIVE: To report signalment, history, indications, complications and outcome for 28 dogs and 5 cats in which 34 permanent epicardial pacing leads were surgically placed by transdiaphragmatic approach (32) or intercostal thoracotomy (2). METHODS: Medical records (2005-2010) were reviewed. Signalment, age, species, gender, clinical signs, presence of structural heart disease and/or congestive heart failure, ECG diagnosis, body weight (<10 or >10 kg), and overall survival rate were recorded. Statistical correlations were made between these variables and major and minor complications rates. RESULTS: Except for body weight, no statistical differences were identified in prevalence of major (life threatening or requiring replacement of the pacemaker system) or minor (self-limiting) complications; dogs weighing >10 kg had significantly more major complications (P = .03). There was a trend (P = .051) for lower survival in animals that had major complications. CONCLUSIONS: Larger dogs (>10 kg) may be predisposed to more major complications with epicardial pacemaker (EP) implantation. Major complication rate and survival time are similar to those reported for transvenous pacing and therefore implantation of EPs remains a suitable alternative.

A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher.

Familial dilated cardiomyopathy is a primary myocardial disease that can result in the development of congestive heart failure and sudden cardiac death. Spontaneous animal models of familial dilated cardiomyopathy exist and the Doberman pinscher dog is one of the most commonly reported canine breeds. The objective of this study was to evaluate familial dilated cardiomyopathy in the Doberman pinscher dog using a genome-wide association study for a genetic alteration(s) associated with the development of this disease in this canine model. Genome-wide association analysis identified an area of statistical significance on canine chromosome 14 (p(raw) = 9.999e-05 corrected for genome-wide significance), fine-mapping of additional SNPs flanking this region localized a signal to 23,774,190-23,781,919 (p = 0.001) and DNA sequencing identified a 16-base pair deletion in the 5' donor splice site of intron 10 of the pyruvate dehydrogenase kinase 4 gene in affected dogs (p < 0.0001). Electron microscopy of myocardium from affected dogs demonstrated disorganization of the Z line, mild to moderate T tubule and sarcoplasmic reticulum dilation, marked pleomorphic mitochondrial alterations with megamitochondria, scattered mitochondria with whorling and vacuolization and mild aggregates of lipofuscin granules. In conclusion, we report the identification of a splice site deletion in the PDK4 gene that is associated with the development of familial dilated cardiomyopathy in the Doberman pinscher dog.

Clinical progression of X-linked muscular dystrophy in two German Shorthaired Pointers.

CASE DESCRIPTION: 2 full-sibling male German Shorthaired Pointer (GSHP) puppies (dogs 1 and 2) with X-linked muscular dystrophy and deletion of the dystrophin gene (gene symbol, DMD) each had poor growth, skeletal muscle atrophy, pelvic limb weakness, episodic collapse, and episodes of coughing. CLINICAL FINDINGS: Initial examination revealed stunted growth, brachygnathism, trismus, and diffuse neuromuscular signs in each puppy; clinical signs were more severe in dog 2 than in dog 1. Immunohistochemical analysis revealed a lack of dystrophin protein in both dogs. During the next 3 years, each dog developed hyperinflation of the lungs, hypertrophy of the cervical musculature, and hypertrophy of the lateral head of the triceps brachii muscle. TREATMENT AND OUTCOME: Monitoring and supportive care were provided at follow-up visits during an approximately 7-year period. No other specific treatment was provided. Neuromuscular signs in both dogs remained stable after 3 years of age, with dog 2 consistently more severely affected than dog 1. The dogs had multiple episodes of aspiration pneumonia; dogs 1 and 2 were euthanatized at 84 and 93 months of age, respectively. CLINICAL RELEVANCE: The clinical course of disease in these dogs was monitored for a longer period than has been monitored in previous reports of dystrophin-deficient dogs. The clinical progression of muscular dystrophy in the 2 GSHPs was compared with that for other breeds and species with dystrophin-deficient conditions, and the potential basis for the phenotypic variation observed between these littermates, along with potential therapeutic ramifications for dogs and humans, was evaluated.

Myxomatous mitral valve disease in Miniature Schnauzers and Yorkshire Terriers: 134 cases (2007-2016).

OBJECTIVE: To characterize features of myxomatous mitral valve disease (MMVD) in Miniature Schnauzers and Yorkshire Terriers. ANIMALS: 69 Miniature Schnauzers and 65 Yorkshire Terriers, each with MMVD. PROCEDURES: Medical record data for each dog were collected; the study period was January 2007 through December 2016. If available, radiographic data were evaluated, and a vertebral heart scale score was assigned for each dog. Statistical analysis was performed with Student t and Fisher exact tests. RESULTS: Compared with Yorkshire Terriers, the prevalence of MMVD was significantly higher in Miniature Schnauzers and affected dogs were significantly younger at the time of diagnosis. Miniature Schnauzers were significantly more likely to have mitral valve prolapse and syncope, compared with Yorkshire Terriers. Yorkshire Terriers were significantly more likely to have coughing and have had previous or current treatment with cardiac medications, compared with Miniature Schnauzers. There was no statistical difference between breeds with regard to abnormally high vertebral heart scale scores or radiographic evidence of congestive heart failure. CONCLUSIONS AND CLINICAL RELEVANCE: With regard to MMVD, features of the disease among Miniature Schnauzers and Yorkshire Terriers were similar, but there were also a few discernable differences between these 2 breeds and from historical findings for dogs with MMVD of other breeds. Clinical signs at the time of diagnosis differed between the 2 breeds, which may have reflected concurrent breed-specific conditions (sick sinus syndrome or airway disease [eg, tracheal collapse]). Future work should include prospective studies to provide additional information regarding the natural progression of MMVD in these dog breeds.

A deleterious mutation in the ALMS1 gene in a naturally occurring model of hypertrophic cardiomyopathy in the Sphynx cat.

BACKGROUND: Familial hypertrophic cardiomyopathy is a common inherited cardiovascular disorder in people. Many causal mutations have been identified, but about 40% of cases do not have a known causative mutation. Mutations in the ALMS1 gene are associated with the development of Alstrom syndrome, a multisystem familial disease that can include cardiomyopathy (dilated, restrictive). Hypertrophic cardiomyopathy has not been described. The ALMS1 gene is a large gene that encodes for a ubiquitously expressed protein. The function of the protein is not well understood although it is believed to be associated with energy metabolism and homeostasis, cell differentiation and cell cycle control. The ALMS1 protein has also been shown to be involved in the regulation of cell cycle proliferation in perinatal cardiomyocytes. Although cardiomyocyte cell division and replication in mammals generally declines soon after birth, inhibition of ALMS1 expression in mice lead to increased cardiomyocyte proliferation, and deficiency of Alstrom protein has been suggested to impair post-natal cardiomyocyte cell cycle arrest. Here we describe the association of familial hypertrophic cardiomyopathy in Sphynx cats with a novel ALMS1 mutation. RESULTS: A G/C variant was identified in exon 12 (human exon 13) of the ALMS1 gene in affected cats and was positively associated with the presence of hypertrophic cardiomyopathy in the feline population (p < 0.0001). The variant was predicted to change a highly conserved nonpolar Glycine to a positively charged Arginine. This was predicted to be a deleterious change by three in silico programs. Protein prediction programs indicated that the variant changed the protein structure in this region from a coil to a helix. Light microscopy findings included myofiber disarray with interstitial fibrosis with significantly more nuclear proliferative activity in the affected cats than controls (p < 0.0001). CONCLUSION: This study demonstrates a novel form of cardiomyopathy associated with ALMS1 in the cat. Familial hypertrophic cardiomyopathy is a disease of genetic heterogeneity; many of the known causative genes encoding for sarcomeric proteins. Our findings suggest that variants in genes involved with cardiac development and cell regulation, like the ALMS1 gene, may deserve further consideration for association with familial hypertrophic cardiomyopathy.

Retrospective evaluation of the safety and tolerability of pimobendan in cats with obstructive vs nonobstructive cardiomyopathy.

BACKGROUND: Pimobendan is frequently used off-label for treatments of cats with congestive heart failure (CHF). Concern exists regarding the safety of pimobendan in cats with outflow tract obstruction (OTO). OBJECTIVES: In cats treated with pimobendan, incidence of adverse effects will not differ between cats with OTO vs cats with nonobstructive cardiomyopathy. ANIMALS: Two-hundred sixty cats with CHF (57 with OTO, 203 with nonobstructive disease). METHODS: Retrospective medical record review. Groups were compared using 2-sample t-tests, Wilcoxon rank-sum tests, and Fisher exact tests. RESULTS: Compared to cats with nonobstructive cardiomyopathy, cats with OTO were younger (8.9 [interquartile range (IQR) 6.6] vs 10.8 [6.3] years, P = .0036), more likely to have a heart murmur (51/57 [90%] vs 76/203 [37.8%] cats, P < .0001), more likely to manifest CHF as pulmonary edema (53/57 [83%] vs 144/203 [70.9%] cats, P = .0004), and less likely to have pleural effusion (19/57 [33%] vs 122/203 [60.1%] cats, P = .0005). Adverse effects suspected to be related to pimobendan administration occurred in 12/260 cats (4.6%), including 11/203 cats (5.4%) with nonobstructive cardiomyopathy and 1/57 cat (2%) with OTO (P = .7). Pimobendan was discontinued due to adverse effects in 4/260 cats (1.5%), 3 with nonobstructive disease and 1 with OTO (P = 1.0). Acute adverse hemodynamic effects after pimobendan administration were not detected in any cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan is well tolerated in cats with cardiomyopathy and CHF, regardless of the presence of OTO.

Assessment of PDK4 and TTN gene variants in 48 Doberman Pinschers with dilated cardiomyopathy.

OBJECTIVE: 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. ANIMALS: 48 Doberman Pinschers with DCM. PROCEDURES: 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. RESULTS: 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. CONCLUSIONS AND CLINICAL RELEVANCE: 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.

Temporal changes in clinical and radiographic variables in dogs with preclinical myxomatous mitral valve disease: The EPIC study.

BACKGROUND: The Evaluation of pimobendan in dogs with cardiomegaly caused by preclinical myxomatous mitral valve disease (EPIC) study monitored dogs with myxomatous mitral valve disease (MMVD) as they developed congestive heart failure (CHF). OBJECTIVES: To describe the changes in clinical and radiographic variables occurring as dogs with MMVD and cardiomegaly develop CHF, compared to similar dogs that do not develop CHF. ANIMALS: One hundred and thirty-five, and 73 dogs that did or did not develop CHF, respectively. MATERIALS AND METHODS: The following variables were evaluated in 2 groups of dogs (dogs that did or did not develop CHF): Heart rate (HR), clinic respiratory rate (RR), home-measured resting respiratory rate (RRR), rectal temperature (RT), body weight (BW), and vertebral heart sum (VHS). Absolute value and rate of change of each variable were calculated for each day a dog was in study. Daily means were calculated and plotted against time. The onset of CHF or last visit before leaving the study were set as reference time points. RESULTS: The most extreme values and rate of change occurred in variables immediately before onset of CHF. Vertebral heart sum increased earliest. Heart rate, RR, and RRR also increased. Rectal temperature and BW decreased. Increases in RR and RRR were most extreme and occurred immediately before CHF. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with MMVD and cardiomegaly experience increases in HR, RR, RRR, and VHS, and decreases in BW and RT as they develop CHF. The variables with highest absolute change and rate of change were RR and RRR. These findings reinforce the value of RR and RRR as indicators of impending or incipient CHF.

ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs.

This report, issued by the ACVIM Specialty of Cardiology consensus panel, revises guidelines for the diagnosis and treatment of myxomatous mitral valve disease (MMVD, also known as endocardiosis and degenerative or chronic valvular heart disease) in dogs, originally published in 2009. Updates were made to diagnostic, as well as medical, surgical, and dietary treatment recommendations. The strength of these recommendations was based on both the quantity and quality of available evidence supporting diagnostic and therapeutic decisions. Management of MMVD before the onset of clinical signs of heart failure has changed substantially compared with the 2009 guidelines, and new strategies to diagnose and treat advanced heart failure and pulmonary hypertension are reviewed.

Long-term incidence and risk of noncardiovascular and all-cause mortality in apparently healthy cats and cats with preclinical hypertrophic cardiomyopathy.

BACKGROUND: Epidemiologic knowledge regarding noncardiovascular and all-cause mortality in apparently healthy cats (AH) and cats with preclinical hypertrophic cardiomyopathy (pHCM) is limited, hindering development of evidence-based healthcare guidelines. OBJECTIVES: To characterize/compare incidence rates, risk, and survival associated with noncardiovascular and all-cause mortality in AH and pHCM cats. ANIMALS: A total of 1730 client-owned cats (722 AH, 1008 pHCM) from 21 countries. METHODS: Retrospective, multicenter, longitudinal, cohort study. Long-term health data were extracted by medical record review and owner/referring veterinarian interviews. RESULTS: Noncardiovascular death occurred in 534 (30.9%) of 1730 cats observed up to 15.2 years. Proportion of noncardiovascular death did not differ significantly between cats that at study enrollment were AH or had pHCM (P = .48). Cancer, chronic kidney disease, and conditions characterized by chronic weight-loss-vomiting-diarrhea-anorexia were the most frequently recorded noncardiovascular causes of death. Incidence rates/risk of noncardiac death increased with age in AH and pHCM. All-cause death proportions were greater in pHCM than AH (65% versus 40%, respectively; P < .001) because of higher cardiovascular mortality in pHCM cats. Comparing AH with pHCM, median survival (study entry to noncardiovascular death) did not differ (AH, 9.8 years; pHCM, 8.6 years; P = .10), but all-cause survival was significantly shorter in pHCM (P = .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: All-cause mortality was significantly greater in pHCM cats due to disease burden contributed by increased cardiovascular death superimposed upon noncardiovascular death.

Comparison of the pharmacokinetic properties of bisoprolol and carvedilol in healthy dogs.

OBJECTIVE: To compare the pharmacokinetic properties and bioavailability following oral and IV administration of bisoprolol, a second-generation beta1-adrenoceptor-selective blocking agent, with those of carvedilol, a third-generation beta1/beta2 and alpha1-adrenoceptor blocking agent, in dogs. ANIMALS: 12 healthy adult Beagles. PROCEDURES: A prospective, parallel group study was performed. The dogs were allocated to 1 of 2 groups (6 dogs/group) and were administered orally a 1 mg/kg dose of either bisoprolol or carvedilol. Following a 1-week washout period, each cohort received a 1 mg/kg dose of the same drug IV. Blood samples were collected before and after drug administration, and serum concentrations, pharmacokinetic variables, and bioavailability for each agent were assessed. RESULTS: After oral administration of bisoprolol, the geometric mean value of the area under the concentration-time curve extrapolated to infinity (AUCinf) was 2,195 microg/L (coefficient of variation [CV], 15%). After IV administration of bisoprolol, the dose-normalized geometric mean AUCinf was 2,402 microg/L (CV, 19%). Oral bioavailability of bisoprolol was 91.4%. After oral administration of carvedilol, the geometric mean AUCinf was 70 microg/L (CV, 81%). After IV administration of carvedilol, the geometric mean AUCinf was 491 microg/L (CV, 23%). Oral bioavailability of carvedilol was 14.3%. Total body clearance was low (0.42 L/h/kg) for bisoprolol and high (2.0 L/h/kg) for carvedilol. CONCLUSIONS AND CLINICAL RELEVANCE: After oral administration, carvedilol underwent extensive first-pass metabolism and had limited bioavailability; bisoprolol had less first-pass effect and higher bioavailability. Collectively, these differences suggested that, in dogs, bisoprolol has less interindividual pharmacokinetic variability, compared with carvedilol.

Use of a nitinol gooseneck snare catheter for removal of adult Dirofilaria immitis in two cats.

CASE DESCRIPTION: 2 cats were examined because of congestive heart failure secondary to heartworm infection. CLINICAL FINDINGS: One cat had severe abdominal distention and the other had dyspnea secondary to chylothorax. Both had loud right-sided heart murmurs, precordial thrills, and jugular distension. Thoracic radiography revealed cardiomegaly and enlarged caudal pulmonary arteries. Echocardiography revealed tricuspid regurgitation and multiple hyperechoic structures consistent with adult Dirofilaria immitis within the right atrium, right ventricle, and main pulmonary artery. Pulmonary hypertension was documented by means of Doppler echocardiography in 1 cat. TREATMENT AND OUTCOME: Cats were anesthetized, and a nitinol gooseneck snare catheter was introduced into the right side of the heart via a jugular venotomy. In the first cat, the snare was used to retrieve 5 female and 2 male adult D immitis. The catheter was then passed into the main pulmonary artery in an unsuccessful attempt to retrieve remaining heartworms. In the second cat, 2 adult female D immitis were removed from the right atrium with the nitinol snare. In both cats, clinical signs resolved within 4 weeks after the procedure. CLINICAL RELEVANCE: Findings suggested that use of a nitinol gooseneck snare catheter may be a safe and effective technique for removing adult D immitis from the right atrium and ventricle in cats and that successful removal of adult heartworms in infected cats may resolve clinical signs of right-sided congestive heart failure and chylothorax. In addition, findings in 1 cat suggested that removal of all adult heartworms may not be necessary for clinical signs to resolve.

International collaborative study to assess cardiovascular risk and evaluate long-term health in cats with preclinical hypertrophic cardiomyopathy and apparently healthy cats: The REVEAL Study.

BACKGROUND: Hypertrophic cardiomyopathy is the most prevalent heart disorder in cats and principal cause of cardiovascular morbidity and mortality. Yet, the impact of preclinical disease is unresolved. HYPOTHESIS/OBJECTIVES: Observational study to characterize cardiovascular morbidity and survival in cats with preclinical nonobstructive (HCM) and obstructive (HOCM) hypertrophic cardiomyopathy and in apparently healthy cats (AH). ANIMALS: One thousand seven hundred and thirty client-owned cats (430 preclinical HCM; 578 preclinical HOCM; 722 AH). METHODS: Retrospective multicenter, longitudinal, cohort study. Cats from 21 countries were followed through medical record review and owner or referring veterinarian interviews. Data were analyzed to compare long-term outcomes, incidence, and risk for congestive heart failure (CHF), arterial thromboembolism (ATE), and cardiovascular death. RESULTS: During the study period, CHF, ATE, or both occurred in 30.5% and cardiovascular death in 27.9% of 1008 HCM/HOCM cats. Risk assessed at 1, 5, and 10 years after study entry was 7.0%/3.5%, 19.9%/9.7%, and 23.9%/11.3% for CHF/ATE, and 6.7%, 22.8%, and 28.3% for cardiovascular death, respectively. There were no statistically significant differences between HOCM compared with HCM for cardiovascular morbidity or mortality, time from diagnosis to development of morbidity, or cardiovascular survival. Cats that developed cardiovascular morbidity had short survival (mean ± standard deviation, 1.3 ± 1.7 years). Overall, prolonged longevity was recorded in a minority of preclinical HCM/HOCM cats with 10% reaching 9-15 years. CONCLUSIONS AND CLINICAL IMPORTANCE: Preclinical HCM/HOCM is a global health problem of cats that carries substantial risk for CHF, ATE, and cardiovascular death. This finding underscores the need to identify therapies and monitoring strategies that decrease morbidity and mortality.

Prospective clinical evaluation of an ELISA B-type natriuretic peptide assay in the diagnosis of congestive heart failure in dogs presenting with cough or dyspnea.

BACKGROUND: B-type natriuretic peptide (BNP) is increased in dogs with congestive heart failure (CHF). HYPOTHESIS: The purpose of this study was to evaluate the clinical utility of a novel canine-specific enzyme-linked immunosorbent assay of BNP for the diagnosis of CHF in dogs presenting with either cough or dyspnea. ANIMALS: Three hundred and thirty dogs from 2 large university teaching hospitals. METHODS: We prospectively measured plasma BNP concentrations in 3 groups of dogs: (1) normal adult dogs (n = 75), (2) dogs with asymptomatic heart disease (n = 76), and (3) dogs with cough or dyspnea (n = 179). The final diagnosis of dogs with cough or dyspnea and the severity of CHF (International Small Animal Cardiac Health Council Heart Failure Classification [ISACHC]) were determined by medical record review by a study cardiologist who was blinded to the results of the BNP assay. RESULTS: Dogs with CHF had a higher median BNP concentration (24.6 pg/mL) than dogs with noncardiac causes of cough or dyspnea (2.6 pg/mL) (P < .0001). The area under the curve was 0.91 for the receiver operating curve analysis of the diagnostic accuracy of the BNP measurement to differentiate CHF from other causes of cough or dyspnea. The median BNP concentrations in dogs were 3.0 pg/mL with ISACHC I, 17.8 pg/mL with ISACHC II, and 30.5 pg/mL with ISACHC III. (P < .0001) CONCLUSION AND CLINICAL IMPORTANCE: Measurement of BNP is useful in establishing or in excluding the diagnosis of CHF in dogs with cough or dyspnea. B-type natriuretic peptide concentrations rose significantly as a function of severity of CHF.