Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Clinical Synopsis
Arrhythmogenic right ventricular dysplasia or cardiomyopathy (ARVD/C) is a heart muscle disease, often familial, that is characterized pathologically by atrophy and fibro-fatty replacement of the right ventricular myocardium and clinically by ventricular arrhythmias of right ventricular origin or sudden death. The progressive loss of the RV myocardium has been related to a genetically determined dystrophic process, an inflammatory myocardial injury and death, or a programmed cell death ("apoptosis"). ARVD/C has been added to the group of cardiomyopathies in the recent revision of classification by the Task Force of the World Health Organization/International Society and Federation of Cardiology
Epidemiology
The incidence and prevalence of ARVC/D are unknown. Patients with a clinical diagnosis of ARVC/D based on typical right precordial ECG changes, right ventricular arrhythmias, and structural and functional RV abnormalities represent only one extreme of the disease spectrum. A number of clinically silent cases are not recognized because they are asymptomatic until the first presentation with sudden death or have been difficult to diagnose by conventional non-invasive tools. A Research Project of the Veneto Region of Italy on sudden death in the young showed that 20% of fatal events in young people and athletes are due to a previously undiagnosed ARVC/D. On the other extreme of the spectrum, patients with congestive heart failure with or without ventricular arrhythmias in whom the diagnosis of ARVD/C was not recognized at the beginning of the evolution represent an other subset of cases often wrongly diagnosed as dilated cardiomyopathy.
Clinical diagnosis
The clinical presentation of ARVD/C peculiarly consists of arrhythmias of right ventricular origin ranging from isolated premature ventricular beats to sustained ventricular tachycardia or ventricular fibrillation leading to sudden death. Other clinical manifestations of the disease include global and/or regional dysfunction and structural alterations of the right ventricle, ECG depolarization/repolarization changes characteristically in right precodial leads, and evolution to right or biventricular heart failure mimicking dilated cardiomyopathy. Until a preclinical, genetic identification of patients with ARVC/D by DNA characterization is possible, the diagnosis should be based on the standardized diagnostic criteria proposed by the Study Group of the Working Group Myocardial and Pericardial Disease of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the International Society and Federation of Cardiology (Table I). These guidelines are based on the presence of major and minor criteria encompassing structural, hystological, electrocardiographic, arrhythmic and genetic factors.
Disease progression and natural history
There is definitive clinico-pathologic evidence that ARVC/D is a progressive heart muscle disease. Clinico-pathologic investigations and long-term follow-up data from clinical studies indicate that ARVC/D with time may lead to a more diffuse RV changes and left ventricular involvement and culminate in heart failure.
The natural history of ARVC/D is a function of both the electrical instability of diseased ventricular myocardium, which can precipitate "arrhythmic" cardiac arrest any time during the disease course, and the progressive myocardial loss that results in ventricular dysfunction and heart failure. The following clinico-pathologic phases can be considered: 1) "concealed" phase characterized by subtle RV structural changes, with or without minor ventricular arrhythmias, during which sudden death may be the first manifestation of the disease, mostly in young people and athletes; 2) "overt electrical disorder" in which severe RV arrhythmias and impending cardiac arrest are associated with overt RV functional and structural abnormalities; 3) "right ventricular failure" due to the progression and extension of the RV muscle disease that provokes global RV dysfunction; 4) final stage of "biventricular pump failure" due to significant LV involvement. At this stage, ARVC mimics a biventricular dilated cardiomyopathy leading to congestive heart failure and thromboembolic complications.
Therapy
Since the assessment of SD risk in patients with ARVC is still not well established, there are no precise guidelines to determine which are the patients who need to be treated and which is the best management approach. The therapeutic options include beta blockers, antiarrhythmic drugs, catheter ablation, and implantable cardioverter defibrillator. In patients in whom ARVD/C has progressed to severe right ventricular or biventricular systolic dysfunction, treatment consists of current therapy for heart failure including diuretics, angiotensin-converting-enzyme inhibitors, and digitalis, as well as anticoagulant therapy. These patients may become candidates for heart transplantation.
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