SNOWMASS, COLO. – Electrophysiologist N.A. Mark Estes III, MD, has a piece of advice for his general cardiology colleagues regarding arrhythmogenic right ventricular cardiomyopathy (ARVC), an inherited arrhythmia syndrome that’s one of the most common causes of sudden death in athletes under the age of 40 years.
“When you have a patient with syncope and an ECG abnormality that suggests ARVC, you immediately restrict activity and immediately go on to imaging. And then it’s time to get that patient off to somebody who deals with these patients all the time,” he said at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.
ARVC is thought to affect 1 in 5,000 people. It’s the cause of sudden death in roughly 5% of young athletes in the United States and 25% in Italy, with the disparity believed to be largely caused by underrecognition of the disease.
Dr. Estes was a coauthor of a 2015 international task force consensus statement on the treatment of ARVC (). An updated report that incorporates much new information is due to be released in May 2019.
“The new guidelines are going to put some very clear limits on physical activity: Less than 7 METs [metabolic equivalents], which is about a brisk walk. Exercise is not good with ARVC,” said, professor of medicine at the University of Pittsburgh.
Patients with ARVC absolutely must be restricted from participation in competitive sports, a step whose importance was demonstrated in the North American Multidisciplinary Study of ARVC, for which Dr. Estes was a coauthor. That study, too recent for inclusion in the 2015 task force consensus statement, showed that competitive sport was associated with a 100% increased risk of ventricular tachyarrhythmias and death, as well as earlier presentation with symptoms, compared with patients with ARVC who engaged in much less intense recreational athletic activity, who in turn didn’t have a risk level any different from inactive patients. That being said, however, the investigators also noted that the absolute risk of ventricular tachyarrhythmias or death remained high even in the inactive and recreational sports participants, at 23% by 2 years post diagnosis ().
ARVC has three phases: An early concealed phase, with an associated high rate of syncope or sudden cardiac death; an intermediate phase marked by frequent arrhythmias; and a late phase involving cardiomyopathy and heart failure. Pathologically, the disease involves progressive loss of myocytes caused by abnormalities of plakoglobin and plakophilin, which Dr. Estes described as “essentially the glue that holds the sarcomeres together.” As myocytes are lost they are replaced by fibrofatty deposits, mostly in the right ventricle, creating a substrate for ventricular arrhythmias.
When to suspect ARVC?
“Anyone who has syncope with exertion automatically has a red flag because there is almost certainly something causing that event that’s potentially malignant,” according to the cardiologist.
An early, sensitive, and reasonably specific hallmark of ARVC on the 12-lead ECG is T wave inversion in right precordial leads V1, V2, and V3 or beyond. An epsilon wave – a small positive deflection at the end of the QRS complex – is present in about one in five patients with ARVC and is diagnostic of the condition.
“It’s an ECG you want to commit to memory. And when you see it, think ARVC,” Dr. Estes advised.
Abnormalities on MRI and 2D echocardiography include right ventricular enlargement and wall motion abnormalities, with left ventricular involvement becoming common in more advanced disease.
The detailed structural, electrographic, functional imaging, histologic, and clinical diagnostic criteria for ARVC, known as the 2010 Task Force Criteria, are readily available (). So are guidelines on genetic testing, which practitioners need to understand is now the standard of care for patients with ARVC and, in the event they are found to have a pathogenic mutation, in first-degree family members as well ( ).
“These days all you need to do is simply Google ‘syncope’ and ‘ARVC’ and you will get to the guidelines,” Dr. Estes advised. “It’s virtually impossible to keep up with all this information, but you should know how to access it and apply it in an individual patient. And learn the role of genetic testing. It’s very much an evolving area, quite mature for the long QT syndromes, but not a robust database for ARVC now. Yet there’s no doubt it’s going to be used more and more for diagnosis, risk stratification, and therapy of ARVC in the future.”
Once the diagnosis of ARVC is made in accordance with the 2010 Task Force Criteria, risk stratification and decision making about definitive therapy become paramount. The international task force consensus statement gives a Class I recommendation to implantable cardioverter defibrillator (ICD) therapy in high-risk ARVC patients, defined as those who’ve had a cardiac arrest, sustained ventricular tachycardia, or have severe right and/or left ventricular dysfunction. ICD therapy gets a Class IIa recommendation in those with at least one of the major risk factors: syncope, nonsustained ventricular tachycardia, and moderate ventricular dysfunction. For ARVC patients with one or more minor risk factors, which include frequent premature ventricular contractions and inducible ventricular tachycardia upon electrophysiological testing, the strength of the recommendation for ICD therapy drops to Class IIb, or “may be considered.” And for low-risk patients, those with confirmed ARVC but no phenotypic expressions of the disorder, the ICD recommendation is Class III, meaning nonindicated.
“There’s a very low threshold for putting in an ICD in patients with ARVC because if you eliminate the arrhythmic mortality, progression to heart failure needing advanced therapies or transplant is extremely rare as long as they’re restricted from athletics,” Dr. Estes said.
He reported serving as a consultant to Boston Scientific, Medtronic, and St. Jude Medical.