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.

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.

Determination of the prevalence of whole blood taurine in Irish wolfhound dogs with and without echocardiographic evidence of dilated cardiomyopathy.

OBJECTIVES: Taurine plays an important role in maintaining myocardial function. Irish wolfhound dogs (IW) are at risk for dilated cardiomyopathy (DCM), but a relationship between whole blood taurine (WBT) deficiency and DCM has not been established. Our aim was to determine prevalence of WBT deficiency in IW with and without DCM and assess its association with diet. ANIMALS: 115 privately owned IW. METHODS: Whole blood taurine was measured in IW that received cardiovascular examination. Dietary history was recorded; crude protein and energy intake were estimated. RESULTS: Forty-nine (42.6%) had DCM; 66 (57.4%) had no DCM. Dogs with DCM were older ([median; inter-quartile range or IQR] 5.3; 4.3, 6.2 years) than dogs without heart disease (3; 2, 4 years; P < 0.001). There was no significant relationship between WBT concentration and age (P = 0.64). Whole blood taurine was severely reduced (<130 nmol/mL) in 8 dogs (4 with and 4 without DCM) and moderately reduced (130-179.9 nmol/mL) in 32 dogs (12 with DCM and 20 without DCM). Follow up of dogs without DCM revealed that a higher proportion of dogs with any degree of WBT deficiency developed DCM later compared to dogs with normal WBT (P < 0.001). CONCLUSIONS: Whole blood taurine deficiency occurred in IW with and without DCM. Based on taurine measurement on a single occasion, there was no clear relationship between low WBT and presence of DCM in this population. Regardless of WBT, DCM affected predominantly older dogs, suggesting a relatively late onset disease in the IW.

Multiple Loci are associated with dilated cardiomyopathy in Irish wolfhounds.

Dilated cardiomyopathy (DCM) is a highly prevalent and often lethal disease in Irish wolfhounds. Complex segregation analysis indicated different loci involved in pathogenesis. Linear fixed and mixed models were used for the genome-wide association study. Using 106 DCM cases and 84 controls we identified one SNP significantly associated with DCM on CFA37 and five SNPs suggestively associated with DCM on CFA1, 10, 15, 21 and 17. On CFA37 MOGAT1 and ACSL3 two enzymes of the lipid metabolism were located near the identified SNP.

Evaluation of tafazzin as candidate for dilated cardiomyopathy in Irish wolfhounds.

Dilated cardiomyopathy (DCM) is a common disease in humans and dogs. Large-breed dogs and especially Irish wolfhounds belong to the frequently affected breeds. Male Irish wolfhounds show a significantly higher prevalence of DCM than females. Therefore, we evaluated X chromosome markers for linkage with DCM as well as a human candidate gene on the X chromosome. A set of X chromosomal microsatellites was genotyped in Irish wolfhound families segregating for DCM. In addition, exon and intron sequences of the tafazzin (TAZ) gene were assayed for polymorphisms segregating in these families. Statistical analysis of the microsatellite markers did not reveal linkage to DCM. Furthermore, all Irish wolfhounds included in this study were monomorphic for TAZ, and only 8 sequence differences to the Dog Genome Assembly 2.1 could be found. The results indicate that due to the lack of mutations, TAZ is unlikely to cause DCM in Irish wolfhounds.

Allometric scaling of M-mode cardiac measurements in normal adult dogs.

Indices for M-mode measurements in dogs usually have been based on the assumption that a linear relationship exists between these measurements and body weight (BW) or body surface area (BSA). The relationships between the geometry of 3-dimensional objects do not support this assumption. The purposes of this study were to retrospectively examine M-mode data from a large number of dogs of varying sizes and breeds that were examined by a large number of ultrasonographers, to use the allometric equation to determine the appropriate BW exponent required to predict these cardiac dimensions, and to determine normal mean values and prediction intervals for common M-mode variables. Linear regression analyses of data from 494 dogs (2.2-95 kg) revealed a good correlation between M-mode measurements and BW after logarithmic transformation of the data (r2 = .55-.88). Most variables were most closely related to an index of body length, BW(1/3), although the exponent that best predicted diastolic and systolic left ventricular wall thicknesses was closer to 0.25. No variable indexed well to BW or BSA. With these data, appropriate mean values and prediction intervals were calculated for normal dogs, allowing veterinarians to correctly and appropriately index M-mode values. The equations developed from this study appear to be applicable to adult dogs of most breeds.

Dilated cardiomyopathy in juvenile doberman pinschers.

BACKGROUND: Canine dilated cardiomyopathy (DCM) is an acquired heart muscle disease of unknown etiology characterized by commonly adult onset of arrhythmias, congestive heart failure(CHF), and sudden death. Myocardial failure associated with myocarditis has been well documented in puppies infected with parvovirus. While a form of DCM has recently been described in juvenile Portuguese Water Dogs it has not been reported in juvenile Doberman pinschers, a breed known for its high prevalence of DCM. METHODS: We examined 7 Doberman pinscher puppies that were referred for cardiovascular examination. Six were from a litter of 8 (2 of the 8 died earlier with congestive heart failure) and an additional puppy was from an unrelated litter. Clinical assessment included physical examination, electrocardiography and echocardiography. Autopsy was performed on 3 puppies from the same litter with echocardiographic documented DCM. Cardiac tissues were evaluated histologically and by PCR analysis for parvovirus. RESULTS: In the litter of 8 puppies, 6 were affected with DCM between 10 days and 4 weeks of age. Of these 6 dogs, 2 died with acute pulmonary edema; 3 were euthanized at 4 weeks of age due to an advanced stage of DCM; 1 was diagnosed with DCM at 11 weeks of age. The latter survived for 2.5 years until it developed CHF and was euthanized. The remaining 2 dogs were unaffected and survived to adulthood. Another puppy from an unrelated litter developed DCM and CHF at 13 weeks of age, and was euthanized 4 weeks later. PCR analysis performed on myocardial tissue was negative for parvovirus genome. Cardiac histopathology revealed extensive myocytolysis involving myocytes and conduction fibers, hyperplasia of myocytes and smooth muscle cells, and attenuated myocytes separated by extracellular edematous ground substance ("wavy fibers"). CONCLUSIONS: A juvenile form of DCM with high morbidity was detected in 6 Doberman pinscher puppies from one litter and in a puppy from an unrelated litter. Congestive heart failure occurred in most of the affected puppies between 10 days and 17 weeks of age.

Proposed guidelines for the diagnosis of canine idiopathic dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality in various dog breeds. The diagnosis of overt DCM is not normally problematic, although the importance of active exclusion of other causes of the dilated, hypokinetic heart is emphasised. Recent interest in human familial DCM has prompted a number of researchers to investigate the genetic basis of canine DCM. Prospective screening of dogs from lines with familial prevalence of DCM may identify dogs with pre-clinical ("occult") DCM. Dogs with other echocardiographic abnormalities or arrhythmias may also be identified. It is clear that dogs, like humans, have a prolonged pre-symptomatic phase of the disease extending over years. The ESVC DCM taskforce was established to provide the veterinary cardiology community with guidelines for the diagnosis of DCM, predominantly based on 2D and M-mode echocardiography. Diagnosis of DCM requires all of the following: (i) Left ventricular dilatation (ii) Reduced systolic function (iii) Increased sphericity of the left ventricle. We propose a scoring system for the identification of dogs in the pre-clinical stages. These include a number of major criteria and minor criteria. Future prospective longitudinal studies are required to test these in different breed populations to assess their predictive power and further refinements may be required. The importance of post mortem confirmation of disease is emphasised, and the two major histopathological features associated with DCM, the attenuated wavy fibre and the fibro-fatty infiltration-degenerative forms, require further investigation to identify the different aetiopathogenetic factors which may be involved.