Feline hypertrophic cardiomyopathy is a challenging disease for veterinarians given its heterogeneous nature and the large segment of HCM cats that are asymptomatic. A genetic basis has been suspected for a long time and recently disease-associated mutations in myosin-binding protein C have been documented in Maine coons and ragdolls1,2. However, phenotypic differences in the disease across the wider spectrum of cats are remarkable. Treatment of asymptomatic cats is still largely empirical and controversial. Treatment of symptomatic cats has evolved over the last few years as data from multicenter clinical trials has become available. Understanding the relation between the disease pathophysiology and the clinical pharmacodynamics of drugs used in the management of this disease is crucial to make appropriate therapeutic decisions.
Objectives Of The Presentation
1. To briefly discuss the pathophysiology of this disease.
Key Pathophysiologic Points
2. To discuss the rationale for potential therapeutic targets.
3. To review the clinical pharmacodynamics of cardiovascular drugs and the results of recent clinical trials on the chronic management of symptomatic HCM.
1. Distinguishing the different forms of feline myocardial disease is not straightforward, which complicates its management.
2. Additionally, end-stage disease acquires certain characteristics that do not fit well into any category3.
3. Hypertrophic cardiomyopathy is defined as a primary myocardial disease characterized by concentric hypertrophy of the nondilated left ventricle (LV) and diastolic dysfunction4,5.
4. Diastolic dysfunction may lead to left atrial dilation, congestive heart failure (CHF), arterial thromboembolism (ATE), and death.
5. Diastolic dysfunction results from a delay in the early relaxation of the heart muscle and increased ventricular stiffness6.
6. Increased stiffness is related to replacement fibrosis and interstitial fibrosis, which are common pathologic findings in HCM7.
7. Decreased cardiac output and hypoxemia lead to activation of the renin-angiotensin-aldosterone system (RAAS), resulting in vasoconstriction, aldosterone-induced sodium and water retention, and sympathetic activation. This has long-term local and systemic deleterious effects.
8. Angiotensin II and aldosterone increase collagen synthesis in cultured cardiac fibroblasts, which may be prevented by receptor antagonists8,9.
9. Aldosterone increases the expression of markers of hypertrophy in rat myocytes10.