Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a rare inherited cardiomyopathy with an estimated prevalence of 1 per 5000 individuals.1 ARVD/C accounts for 11% to 22% of cases of sudden cardiac death (SCD) among young individuals under the age of 35 years.2
ARVD/C typically presents in the second to fifth decades of life, in individuals who are highly athletic. Patients present typically with symptoms associated with ventricular arrhythmias (eg, syncope, palpitations, lightheadedness, and sudden death).2
To shed light on this complex condition, Cardiology Advisor interviewed Hugh Calkins, MD. Dr Calkins is the Nicholas J. Fortuin MD professor of cardiology and professor of medicine, director of the Cardiac Arrhythmia Services and director at the Johns Hopkins ARVD/C Program. He is a coauthor of the International Task Force Consensus Statement on the treatment of ARVD/C.3 Dr Calkins has published more than 50 manuscripts on ARVD/C and directs the largest comprehensive ARVD/C program in the world.
What exactly is ARVD/C?
ARVD/C is rare inherited cardiomyopathy characterized by replacement of the cardiac myocytes with fibrofatty tissue.2 This predisposes patients to ventricular arrhythmias, right ventricular failure, and increased risk of sudden cardiac death (SCD). While ARVD/C primarily affects the right ventricle (RV), it is now understood that involvement of the left ventricle (LV) may also occur. Whether the LV or RV is involved depends to a large degree on the particular genetic mutation associated with the disease.2
How did you become involved in researching and treating this condition?
The first major description of ARVD/C was published in 1982 as a case report of 24 patients with unusual RV cardiomyopathy.4 My involvement began 17 years ago, when I recommended an implantable cardioverter defibrillator (ICD) to a patient with ARVD/C who was at risk of SCD. She decided to postpone implantation and died before the procedure could be done. Her younger brother, who also had early evidence of the disease, suggested starting a program focusing specifically on ARVD. Responding to this tragic case, we started the Johns Hopkins ARVD/C Program to further the scientific understanding of ARVD/C, educate the medical and patient communities, and serve as a referral center. Since then, there have been tremendous advances in understanding and treating this condition.
Is ARVD/C a genetic condition?
Definitely. The inheritance pattern is typically autosomal dominant, meaning that the offspring of the genetically affected probands have a 50% risk of inheriting the abnormal gene.1 But having a gene mutation does not mean that the person will necessarily develop clinical signs of the disease.
The most common genetic mutations in the United States are desmosomal. Desmosomes are proteins that facilitate the mechanical coupling between individual cells, thereby functioning as “glue” to hold cardiac cells together. Under ordinary circumstances, desmosomal proteins are a part of the cell membrane. But in ARVD/C, the desmosomes are disrupted and some components remain intracellular. Over time, the myocardial cells become scarred and there is fibrofatty infiltration of the myocardial wall. Smooth muscle gets replaced by scarring and fat, which set off the arrhythmias.1-2
ARVD/C can also be inherited in an autosomal recessive pattern, as part of a cardiocutaneous syndrome, such as Naxos disease or Carvajal syndrome.1 However, this occurs less frequently in the United States. Some common mutations are listed in Table 1. Since mutations in desmosomal proteins can be identified in only approximately 60% of ARVD/C patients, lack of an identifiable mutation does not definitively exclude the disease.1