Arrhythmogenic right ventricular cardiomyopathy in dogs

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease seen in dogs, cats, and humans. A common entity in Boxers and the related English bulldog, the disease is characterized by fatty or fibrofatty replacement of the myocardium, ventricular arrhythmias, and the potential for syncope or sudden death. In some individuals, concomitant left ventricular involvement results in systolic dysfunction and a progression to congestive heart failure. The clinical and pathological characteristics of ARVC share many similarities in dogs and humans, and Boxers serve as an important spontaneous model of the disease.

Although multiple mechanisms have been implicated in the pathogenesis of ARVC, the disease is ultimately considered to be a disorder of the desmosome. Multiple causal genetic mutations have been identified in people, and over 50% of affected humans have an identifiable mutation in desmosomal proteins. To date, only a single genetic mutation has been associated with ARVC in Boxer dogs. Other as-yet-undiscovered genetic mutations and epigenetic modifiers of the disease are likely. Treatment of ARVC in dogs is focused on controlling ventricular arrhythmias and associated clinical signs. This article will review the pathophysiology, clinical diagnosis, treatment, and prognosis of ARVC in the dog.

Introduction

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of syncope and sudden cardiac death in people and Boxer dogs [1]. It has also been described in the related English bulldog [[2], [3], [4]] and in isolated reports in a Labrador Retriever, Dachshund, Bullmastiff, Siberian husky, Shetland sheepdog, Dalmatian, and Weimaraner [[5], [6], [7], [8], [9]].

The disease is a common entity in the Boxer breed manifested by malignant ventricular arrhythmias, cardiac dilation, and systolic dysfunction, or both. As such, the Boxer serves as an important animal model for the disease in people. The earliest clinically recognizable stage of ARVC is characterized by the development of asymptomatic ventricular arrhythmias originating from the right ventricle (RV). At this stage, routine electrocardiographic (ECG) monitoring may identify infrequent ventricular premature complexes (VPCs) and lead to clinical suspicion of disease, but a definitive diagnosis is established from a combination of family and clinical history signalment, 24-h ambulatory ECG (Holter) monitoring, and echocardiography.

Mutations in various desmosomal proteins are identified in approximately 50% of human patients with ARVC [10]. However, to date, only a single genetic mutation, an eight base pair deletion in the striatin gene, has been found in association with the disease in Boxer dogs [11,12]. The disease is characterized by incomplete penetrance and variable disease expressivity, and striatin genotype is inconsistently associated with disease phenotype. From nine to 16% of dogs with clinical ARVC do not carry the striatin mutation and other genetic causes and nongenetic modifiers of disease expression are likely [[11], [12], [13]].

The histopathologic changes associated with ARVC in Boxers bear a striking resemblance to those accompanying ARVC in people, being characterized by fibrofatty replacement of cardiomyocytes and varying degrees of myocarditis [1]. Replacement of normal cardiomyocytes by inflammatory cells, fibrosis, and adipocytes results in an arrhythmic substrate that sets the stage for the development of malignant re-entrant ventricular arrhythmias. Worsening ventricular arrhythmias can result in clinical signs of weakness, syncope, or sudden death. Some proportion of dogs and people with ARVC will go on to develop left ventricular (LV) involvement with cardiac dilation and reduced LV contractile function, often progressing to overt heart failure [14,15]. Current pharmacologic therapy for ARVC is aimed at palliative relief of clinical signs and malignant arrhythmias, and the search for novel therapeutic targets is ongoing. This article reviews the clinicopathological features, etiopathogenesis, and current screening and treatment options for dogs with ARVC.