Web Chapter 58 In cats most forms of heart disease principally affect the myocardium (Fox, 2003, 2004, 2009, 2010; Fox et al, 1995, 2000, 2007). Cardiomyopathy (cardio-, “heart,” myopathy, “muscle disease”) describes a heterogeneous class of conditions whose dominant features include structural abnormalities or functional impairment of the heart muscle. As such, it excludes conditions resulting from valvular, hypertensive, vascular, pericardial, pulmonary, or congenital derangements. A variety of schemes have been proposed to define the cardiomyopathies. Historically, the term idiopathic (primary) cardiomyopathy has been applied to indicate that the myocardium is the sole source of heart disease when a cause cannot be identified, whereas secondary cardiomyopathy has denoted heart muscle disease resulting from identifiable systemic, metabolic, or nutritional disorders. This original classification was expanded by the World Health Organization (WHO)/International Society and Federation of Cardiology Task Force to include four types of idiopathic heart muscle disease (Richardson et al, 1996): hypertrophic, dilated, restrictive, and arrhythmogenic right ventricular cardiomyopathy (ARVC). However, cardiomyopathies are exceedingly complex disorders and in many circumstances do not fit into a simple category. Newer schemes have evolved to classify cardiomyopathy in humans using insights gained though molecular genetics as well as descriptions of novel ion channelopathies that are now regarded as representing primary forms of cardiomyopathy (Maron et al, 2006). Although these advances provide hypothetical mechanisms and a theoretical framework for cardiomyopathies in the cat, the classification of feline cardiomyopathies has continued to follow to the earlier WHO scheme because of the slower pace of molecular investigation in the cat. ARVC is a clinically heterogeneous heart muscle disease that often is associated with right-sided congestive heart failure (CHF), arrhythmias, and death. It is the least common of the four classic types of idiopathic feline heart muscle diseases (Fox et al, 2007; Fox, 2009, 2010) and accounts for approximately 2% to 4% of myocardial diseases diagnosed in the author’s practice. The causes and pathogenesis of feline ARVC are unresolved. In affected humans the genetic background mostly involves mutations encoding components of the cardiac desmosome (organized intercellular junctions). Dysfunctional desmosomes result in defective cell adhesion proteins including plakoglobin, desmoplakin-2, desmoglein-2, and others, which results in loss of cardiac myocyte electrical coupling and subsequent cell injury (myocyte death) and repair (fibrofatty replacement) (Azaouagh et al, 2011; Murray, 2012; Xu et al, 2010). In humans, ARVC develops during adolescence or young adulthood (Bauce et al, 2011), and this pattern has been observed in affected cats. The disease spectrum of ARVC in humans is more diverse than originally described (Maron et al, 2006; Rizzo et al, 2012), and it has become increasingly apparent that the disorder extends to include biventricular and even left ventricular (LV) forms in some patients. This has given rise to the term arrhythmogenic cardiomyopathy to describe ARVC (Rizzo et al, 2012). Similar phenotypes occur in cats with ARVC (Ciaramella et al, 2009). ARVC also has been shown to be a familial disease in the boxer dog, characterized by ventricular arrhythmias, fatty and fibrofatty myocardial replacement, apoptosis, and myocarditis (Basso et al, 2004). ARVC in the boxer is inherited as an autosomal-dominant trait with incomplete and age-related penetrance and variable clinical expression (Meurs et al, 1999, 2010; see Chapter 179). A deletion in the striatin gene on chromosome 17 has been associated with ARVC in the boxer dog. Striatin has been localized to the intercalated disk region of the cardiac myocyte and to the desmosomal proteins plakophilin-2, plakoglobin, and desmoplakin gap junction proteins that are involved in the pathogenesis of ARVC in humans. Familial tendencies of ARVC have been observed in cats, but pedigree analysis is lacking, and neither specific gene mutations nor defective coded proteins have been identified. Morbidity and mortality of ARVC in dogs (Basso et al, 2004; Meurs et al, 1999, 2010), cats (Fox, 2009; Fox et al, 2000, 2007), and human beings (Marcus et al, 2007) is associated with progressive atrophy of the right ventricular (RV) myocardium with fibrous or fatty replacement. Gap junction remodeling (Kaplan et al, 2004) secondary to altered mechanical coupling may promote arrhythmogenicity. Because desmosomes lend cells mechanical integrity and stability, impaired function of cell adhesion junctions during shear stress may promote inflammation, myocyte detachment, myocyte death, and fibrolipomatous repair (Sen-Chowdhry et al, 2005). Abnormal myocardial structure and function are accelerated by myocarditis, programmed cell death, and fibrous and fatty infiltrates. Apoptosis is present in a high percentage of cats with ARVC (Fox et al, 2000) as in dogs (Basso et al, 2004) and human patients (Valente et al, 1998). Both apoptosis and myocarditis in affected cats may contribute to myocyte injury and repair in susceptible felines. Atrophy of RV myocardium with fibrofatty replacement reduces cardiac reserve and provokes right-sided CHF. RV dilation and remodeling alters the geometry and function of the tricuspid valve apparatus and results in tricuspid valve insufficiency, which further impairs function of the right side of the heart. Histopathologic changes in ARVC are not confined to the RV, and similar but less marked lesions of myocardial injury and repair may be present in the ventricular septum or LV free wall in humans (Rizzo et al, 2012) and cats (Fox, 2009; Fox et al, 2000, 2007). This suggests that in ARVC the disease process may progress over time to involve the LV (Ciaramella et al, 2009; Corrado et al, 1997). Affected cats range in age from 1 to 20 years. Right-sided CHF most often is detected in middle-age cats (Fox et al, 2000). No sex predilection has been documented. ARVC has been detected in many breeds, and particularly in domestic shorthair and Birman cats by the author. Clinical signs most commonly are associated with right-sided CHF, and these include tachypnea and dyspnea. Some cats exhibit nonspecific findings such as lethargy and anorexia before respiratory signs (Fox et al, 2000; Harvey et al, 2005). Syncope has been documented with ventricular tachycardia but is uncommon. Many cats are asymptomatic and are diagnosed following echocardiographic evaluation for heart murmur or arrhythmia. A wide spectrum of arrhythmias have been recorded in ARVC, among which are supraventricular tachyarrhythmias (particularly atrial fibrillation), complex ventricular ectopy including ventricular tachycardia (of right and left ventricular origin), and major conduction abnormalities (Fox et al, 2000). Ventricular tachycardia may be sustained in some cases. The frequency of atrial fibrillation is understandable because of the severe right atrial (RA) enlargement that usually is associated with RV dilatation. Ambulatory (24-hour Holter) electrocardiographic recordings can be useful to document or characterize complex arrhythmias.
Arrhythmogenic Right Ventricular Cardiomyopathy in Cats
Incidence
Causes and Pathogenesis
Pathophysiology
Clinical Presentation
Electrocardiography
