Arrhythmogenic Right Ventricular Dysplasia

Abstract & Commentary

By John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco is a consultant for Novartis, and does research for Medtronic and Guidant.

Synopsis: There is a wide variation in presentation and course of ARVD patients, which can likely be explained by the genetic heterogeneity of the disease.

Source: Dalal D, et al. Arrhythmogenic Right Ventricular Dysplasia: A United States Experience. Circulation. 2005: 112:3823-3832.

Arrhythmogenic right ventricular dysplasia (ARVD) was first described by Fontaine in 1977. The syndrome is characterized by right ventricular dysfunction and ventricular arrhythmias. Most of the clinical series have described features of ARVD found in small series of patients, mostly from European countries. In 1998, the group at Johns Hopkins began a registry of US ARVD patients. This report describes the clinical features of the first 100 patients in this registry.

Patients were referred to the registry by clinicians, either when a diagnosis was made while the patient was alive or if the diagnosis was made at autopsy. In the living patients, the results of noninvasive testing including ECG, signal averaged ECG, Holter monitoring, echocardiograms, and MRI were collected. The diagnosis of ARVD was established on the basis of the criteria set up by a previous task force. Diagnosis at autopsy was made by the classic histopathologic signs of RV myocardial loss associated with fatty or fibrofatty infiltration.

The registry population included 100 patients. Sixty-nine of the 100 patients received the diagnosis while living, and 31 were diagnosed with ARVD on autopsy. The group included 51 men and 49 women. Almost all (95%) were Caucasian. Thirty-two of the patients from 19 families had evidence for a familial form of ARVD.

Palpitations, syncope, and death were the most common presenting symptoms. Only 15 of the 100 patients were asymptomatic at the time of diagnosis. A sustained ventricular arrhythmia leading to sudden cardiac arrest was the first manifestation of ARVD in 22 patients. Only one of these patients survived the presenting episode. Among the patients diagnosed while alive, the most common imaging findings were dilatation and reduction of right ventricular ejection fraction with no left ventricular systolic impairment. RV dysfunction was severe in 21 of 69 patients and mild in 36 of 69. Regional right ventricular hypokinesis was seen in 37 of 69 patients. The most common electrocardiographic abnormalities were prolongation of the QRS in leads V1 thru V3 (58%) and T wave inversions in V1 thru V3 or beyond (81%). Epsilon waves were seen in only 29%. The signal averaged ECG was abnormal in 67% of patients. Ventricular tachycardia with a left bundle branch block morphology was observed in 77% of the patients, and 67% had frequent ventricular extrasystoles.

For the patients who were diagnosed while alive, the median age at presentation was 29 years, with only one patient presenting before age 12. The initial presentation was symptomatic sustained VT in 26 of 69 patients, and 9 additional patients later developed sustained VT. After diagnosis, 31 of the 35 patients with a sustained arrhythmia underwent placement of an ICD, whereas 4 patients were treated with drug therapy alone. Among the patients with an ICD, 26 of 47 (62%) received appropriate ICD therapy during follow-up. Three of the 15 ICD recipients who had previously been asymptomatic received ICD therapy after their implant.

Among the patients in whom ARVD was diagnosed at autopsy, the median age was 24. Sudden cardiac arrest occurred during routine activity in 18, during exercise in 9, during pregnancy in one, and during sleep in one. At autopsy, right ventricular dilatation was moderate-to-severe in 9 patients, but only mild in 20 patients. Inflammatory infiltrates were seen in 7 prior to death, and 5 of 31 patients had one or more known episodes of syncope.

During follow-up, 6 patients developed right-sided heart failure and one progressed to biventricular heart failure. Two patients died of causes other than ARVD. Two additional patients developed incessant VT and underwent cardiac transplantation.

Dalal and colleagues conclude that data from this registry will provide important information about the natural history of ARVD, and may provide insights into its underlying mechanisms.

Commentary

This paper provides important information about the long-term natural history of patients with ARVD. Early reports on series of patients with sustained ventricular tachycardia (VT) with left bundle ECG morphology, often included both patients with AVD and those with more benign forms of RV outflow tract tachycardia. As ARVD became to be clearly recognized as a distinct syndrome, criteria for the diagnosis of ARVD were established to differentiate patients with benign forms of RV VT from those with ARVD. The registry data presented in this paper confirm that this syndrome is important chiefly because of the arrhythmias which characterize it. In several European series, many patients had a severe and progressive cardiomyopathy, but progressive heart failure seems to be much less important in North America. The reason for this remains unknown, but it is likely that ARVD includes several different causes and clinical manifestations. Even though right ventricular dysfunction can be quite marked, congestive heart failure is uncommon and rarely severe. Therefore, if ventricular arrhythmias can be controlled, mortality should be low.

Unfortunately, the arrhythmia pattern in ARVD patients can be highly variable. Some patients have relatively rare episodes of ventricular tachycardia, and ICD therapy, with or without antiarrhythmic drugs, should be highly effective. Other patients, however, have frequent or even incessant arrhythmias. In these patients, catheter ablation may be used to improve the arrhythmia pattern, even though total control is unusual.

We can expect in the future years to hear more data from the ARVD Registry. Of particular interest will be more information about the genetic basis for the disorder, which will hopefully allow us to be more certain in our diagnostic approach.