BackgroundPimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown.Hypothesis/ObjectivesAdministration of pimobendan (0.4–0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac‐related death, or euthanasia.Animals360 client‐owned dogs with MMVD with left atrial‐to‐aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5.MethodsProspective, randomized, placebo‐controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac‐related death, or euthanasia.ResultsMedian time to primary endpoint was 1228 days (95% CI: 856–NA) in the pimobendan group and 766 days (95% CI: 667–875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47–0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952–NA) in the pimobendan group and 902 days (95% CI: 747–1061) in the placebo group) (P = .012).Conclusions and Clinical ImportanceAdministration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.

Background-Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary familial heart muscle disease associated with substantial cardiovascular morbidity and risk of sudden death. Efforts to discern relevant pathophysiological mechanisms have been impaired by lack of a suitable animal model. Methods and Results-ARVC was diagnosed in 23 boxer dogs (12 male; 9.1Ϯ2.3 years old). Clinical events alone or in combination included sudden death (nϭ9; 39%), ventricular arrhythmias of suspected right ventricular (RV) origin (nϭ19; 83%), syncope (nϭ12, 52%), and heart failure (nϭ3; 13%). Right ventricular enlargement or aneurysms occurred in 10 (43%). Striking histopathological abnormalities were present in each boxer dog but not in controls, including severe RV myocyte loss with replacement by fatty (nϭ15, 65%) or fibrofatty (nϭ8, 35%) tissue. Focal fibrofatty lesions were also present in both atria (nϭ8) and the left ventricle (LV) (nϭ11). Fatty replacement occupied substantially greater RV wall area in ARVC dogs than controls (40.4Ϯ18.8% versus 13.8Ϯ3.4%, respectively) (PϽ0.001); residual myocardium was correspondingly reduced (56.6Ϯ19.2% versus 84.8Ϯ3.8% in controls) (PϽ0.001). MRI demonstrated bright anterolateral and/or infundibular RV myocardial signals, confirmed as fat by histopathology. Myocarditis appeared in the RV (nϭ14, 61%) and LV (nϭ16, 70%) and in each dog with sudden death, but not in controls. Familial transmission was evident in 10 of the 23. Key Words: models, animal Ⅲ cardiomyopathy Ⅲ pathology Ⅲ death, sudden A rrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary familial cardiomyopathy associated with substantial cardiovascular morbidity and sudden death in the young. 1-3 ARVC is transmitted as an autosomal dominant trait, and 2 mutations have been identified at the cardiac ryanodine receptor 2 gene (ARVD2) and the desmoplakin gene (ARVD8). 4,5 It has been noted for many years that the boxer canine breed is predisposed to ventricular arrhythmias and sudden death, 6,7 but the underlying disease responsible for these clinical features has been incompletely defined. In light of advances in genomic mapping of the domestic dog, 8 a spontaneous canine model of ARVC and sudden death would provide a unique opportunity to study this disease genome and contribute valuable insights into its pathogenesis. Therefore, the purpose of the present study was to define the clinical and pathological features of a naturally occurring myocardial disease in boxer dogs and assess its suitability as an animal model of ARVC. Conclusions-We Methods Selection of Animal SubjectsAs part of an ongoing study to evaluate the heritability of ventricular arrhythmias in boxer dogs, 239 such animals, including 6 large families, were prospectively recruited for Holter ECG between 1997 and 1999 at the Ohio State University College of Veterinary Medicine. Of those with substantial ectopy or syncope that died or were euthanized, 23 boxer dogs (12 male, 11 female) had autopsy examination and constitute the study group....

BackgroundChanges in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described.ObjectivesTo investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac‐related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan‐treated dogs differ from dogs receiving placebo at onset of CHF.AnimalsThree hundred and fifty‐four dogs with MMVD and cardiomegaly.Materials and MethodsProspective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4–0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart‐size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short‐term changes in echocardiographic variables and time to CHF or CRD were explored.ResultsAt day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN −0.06 (IQR: −0.15 to +0.02), P < 0.0001, and LA:Ao −0.08 (IQR: −0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar.Conclusions and Clinical ImportancePimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.

The purposes of this study were to evaluate families of Boxers with ventricular arrhythmias to determine whether this disorder is a familial trait and, if so, to determine the mode of inheritance. Eighty-two Boxers were evaluated by physical examination, electrocardiogram, echocardiogram, and 24-hour ambulatory electrocardiogram. Dogs were considered affected if at least 50 premature ventricular complexes (PVCs) were observed during a 24-hour period. All dogs were at least 6 years of age at evaluation. Complete cardiovascular examinations were performed on dogs from 6 extended families. The 2 most complete pedigrees were used to determine the pattern of inheritance. The number of PVCs observed during a 24-hour period in affected dogs ranged from 112 to 4,894 (mean Ϯ SD, median; 1,309 Ϯ 2,609, 1,017). The number of PVCs observed during a 24-hour period in the unaffected dogs ranged from 0 to 16 (7 Ϯ 10, 12). Pedigree evaluation was performed to determine pattern of inheritance. An autosomal dominant pattern was determined to be most likely because a sex predisposition was not observed, affected individuals were observed in every generation, and 2 affected individuals produced unaffected offspring. We conclude that familial ventricular arrhythmias is inherited as an autosomal dominant trait in some Boxers.