**4. Feline HCM**

### **4.1. Etiology and pathogenesis**

Recent report suggested that feline cardiomyopathy may be classified as HCM, hypertrophic obstructive cardiomyopathy (HOCM), restrictive cardiomyopathy (RCM), dilated cardiomy‐ opathy, arrhythmogenic right ventricular cardiomyopathy, and unclassified cardiomyopathy (UCM) based on echocardiography and other factors [12]. However, diagnosis is quite challenging because of complexity of the disease. Feline idiopathic HCM is the most commonly diagnosed heterogeneous disease, which is transmitted in autosomal dominant trait in some specific breeds [15]. The disease is more frequent in male than in female. Genetic mutations in gene encoding in sarcomere protein myosin‐binding protein C (MYBPC3) is associated with the development of disease in Manine Coon Cats (A31P mutation) and Ragdoll Cats (R820W mutation) [18]. Other breeds including Domestic Short Hair, Norwegian Forest Cats, Sphinx, Bengals, Chartreux, British Shorthairs, European, Scottish Folds, Cornish Rex, and Persian breeds are also high in disease prevalence but causative mutations associated with disease have yet to be documented [11, 15, 16]. In addition to specific gene mutation, feline myocardial hypertrophy results from possible causes such as an excessive production of catecholamines, myocardial ischemia, fibrosis, primary collagen abnormality, and abnormalities in myocardial calcium‐handling process [15].

### **4.2. Pathophysiology**

The disease is characterized by papillary muscle and LV hypertrophy, systolic anterior motion (SAM) of the mitral valve, diastolic dysfunction, end‐systolic cavity obliteration, and enlarge‐ ment of the left atrium [14, 35]. Abnormal sarcomere function results from myocyte hypertro‐ phy and increased collagen synthesis. Asymmetric or symmetric LV free‐wall concentric hypertrophy with interventricular septum is the characteristic form of the disease [36]. Some have limited abnormality in the basal septum and/or papillary muscles. These different patterns of hypertrophy may be caused by different phenotypic expression between different breeds.

Myocardial hypertrophy and reduced ventricular distensibility result in increased diastolic pressure and LV filling accompanying increased left arterial (LA) and pulmonary venous pressure. Secondary right‐sided congenital heart failure (CHF) may occur in response to prolonged pulmonary vasoconstriction and increased pulmonary arterial pressure. LV outflow obstruction accompanying ejection murmur results from LV papillary muscle hypertrophy. Several factors contribute to myocardial ischemia, which leads to fibrosis, arrhythmias, and other complications. CHF, arterial thromboembolism (ATE), and sudden cardiac death are common clinical manifestation in end‐stage feline HCM [15].

### **4.3. Histologic description**

including the cases with asymptomatic arrhythmias, ventricular tachyarrhythmias, cardiac arrhythmias, and congestive heart failure [34]. The disease appears to have an autosomal dominant inherited pattern. The Boxers with cardiac arrhythmias and congestive heart failure is considered to be a form of canine DCM, which is characterized by left and right ventricular myocardial systolic dysfunction [15, 23]. Histologic form of the disease includes myofibers atrophy, fibrosis, and fatty infiltration in the right ventricular wall. Deletion in the desmosomal striatin gene is associated with the disease developed in Boxer with ARVC [23]. The prognosis is varied in the forms of disease but survival is less than 6 months in case of CHF. Sudden death

Recent report suggested that feline cardiomyopathy may be classified as HCM, hypertrophic obstructive cardiomyopathy (HOCM), restrictive cardiomyopathy (RCM), dilated cardiomy‐ opathy, arrhythmogenic right ventricular cardiomyopathy, and unclassified cardiomyopathy (UCM) based on echocardiography and other factors [12]. However, diagnosis is quite challenging because of complexity of the disease. Feline idiopathic HCM is the most commonly diagnosed heterogeneous disease, which is transmitted in autosomal dominant trait in some specific breeds [15]. The disease is more frequent in male than in female. Genetic mutations in gene encoding in sarcomere protein myosin‐binding protein C (MYBPC3) is associated with the development of disease in Manine Coon Cats (A31P mutation) and Ragdoll Cats (R820W mutation) [18]. Other breeds including Domestic Short Hair, Norwegian Forest Cats, Sphinx, Bengals, Chartreux, British Shorthairs, European, Scottish Folds, Cornish Rex, and Persian breeds are also high in disease prevalence but causative mutations associated with disease have yet to be documented [11, 15, 16]. In addition to specific gene mutation, feline myocardial hypertrophy results from possible causes such as an excessive production of catecholamines, myocardial ischemia, fibrosis, primary collagen abnormality, and abnormalities in myocardial

The disease is characterized by papillary muscle and LV hypertrophy, systolic anterior motion (SAM) of the mitral valve, diastolic dysfunction, end‐systolic cavity obliteration, and enlarge‐ ment of the left atrium [14, 35]. Abnormal sarcomere function results from myocyte hypertro‐ phy and increased collagen synthesis. Asymmetric or symmetric LV free‐wall concentric hypertrophy with interventricular septum is the characteristic form of the disease [36]. Some have limited abnormality in the basal septum and/or papillary muscles. These different patterns of hypertrophy may be caused by different phenotypic expression between different

Myocardial hypertrophy and reduced ventricular distensibility result in increased diastolic pressure and LV filling accompanying increased left arterial (LA) and pulmonary venous

is common in asymptomatic cases.

336 Cardiomyopathies - Types and Treatments

**4.1. Etiology and pathogenesis**

calcium‐handling process [15].

**4.2. Pathophysiology**

breeds.

**4. Feline HCM**

Gross anatomy is characterized by moderate to severe papillary muscle and LV concentric hypertrophy (**Figure 1**). Histologic findings based on hematoxylin and eosin (HE) staining and other specific markers revealed several abnormalities including multifocal myocardial interstitial fibrosis, myofiber disarray, diffuse myocyte hypertrophy with or without scattered individual cell necrosis, and arteriosclerosis in papillary muscles in the LV wall, interventric‐ ular septum, and intramural coronary artery [10, 37]. Recent evidence showed remodeling of the myofibrils and interfibrillar mitochondria, sarcolemmal remodeling with depletion of the subsarcolemmal mitochondria, changes of Z‐disc morphology, myofibrillar degeneration, and endomysial fibrosis based on electron microscopic examination [10].

**Figure 1.** Gross morphologic features of heart from feline with HCM. (A) Overview of the heart from feline HCM. (B) Hypertrophy of ventricular septum (VS) in relation to left ventricular (LV) free wall. RV = right ventricle. Images cour‐ tesy of Prof. Kinji Shirota.

#### **4.4. Survival and prognosis**

Some prognostic factors such as heart rate and LA size are associated with survival time [12]. The prognosis is worse in case with ATE and/or CHF. Restrictive cardiomyopathy may be a consequence of the end stage of myocardial failure and infarction caused by HCM. Several factors cause a secondary RCM including tumor and infectious disease that were documented [15]. The prognosis is poor for feline with RCM accompanied by heart failure.
