Inherited SCD syndromes: Management of family members and asymptomatic "carriers"

Approximately 5% of patients resuscitated from cardiac arrest due to ventricular fibrillation or polymorphic ventricular tachycardia have no evidence of structural heart disease despite extensive clinical evaluation. Some of these patients are eventually found to be carriers of genetic defects that cause a "cardiac channelopathy," such as the long QT syndrome (LQTS), Brugada syndrome, progressive cardiac conduction disease, catecholaminergic polymorphic ventricular tachycardia, and Anderser's cardiodysrhythmic periodic paralysis. Manag ing these individuals remains a challenge, especially given the fact that in some of these individuals, the first and sometimes only symptom is sudden cardiac death (SCD). Knowledge gained in genetics over the years at least has allowed for the categorization and grouping of many syndromes, leading to more effective diagnosis, prognosis, and counseling regarding outcomes and recurrences. Additionally, molecular genetics has led to a greater understanding of the etiology of certain forms of these diseases. Although genetic diseases are less prevalent than acquired diseases, many of them are not uncommon and therefore account for morbidity and mortality of a significant proportion of subjects. For example, it has been estimated that more than 12 million individuals in the world carry the genetic defect for familial hypertrophic cardiomyopathy (HCM), including more than 600,000 individuals in the United States and 50,000 in Canada. Similarly, Brugada syndrome, and LQTS are rather common causes of such deaths in individuals without structural heart disease. Once such an inherited sy ndrome is detected, often following a SCD of a young individual, a critical issue is how to manage family members and asymptomatic "carriers." Management strategies for genetic diseases a remainly based on probands; that is, the family member through whom a family medically comes to light. According to Silvia G. Priori, MD, PhD, the problem of basing management strategies on probands is that they are often the sickest patients in a family, creating a bias that may not be appropriate for family members who often have less penetrant forms of these diseases. So, what constitutes good clinical management of families with genetic diseases and those individual family members determined to have milder, asymptomatic disease but who are still clinically affected? When is it necessary to be aggressive and when is it better to be less aggressive in medical management? The answers are not easy and they are made even more difficult by worried family members who often put tremendous pressure on clinicians when there is any history of SCD in the family. Yet, Dr. Priori emphasizes, clinical management decisions should be very much disease- and patient-specific.