Evaluation of the risk of sudden death in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is defined as primary hypertrophy of the heart muscle, usually the left ventricle which is not dilated. HCM is a rel atively common disease with a prevalence estimated at about 1 in 500. It is a complex disease with relatively stereotypical anatomical features but a very variable clinical presentation with a major risk of complication. All forms may be observed from almost asymptomatic hypertrophy to severe famili al forms with multiple cases of sudden death. Over the last few years, mole cular studies of the genetic abnormalities responsible for HCM have improve d our understanding of the clinical variability of this disease. Schematically, HCM is caused by mutation of one of 4 genes which code the p roteins of the sarcomere : the gene of the heavy chain of beta-myosin, the gene of cardiac T-troponin, the gene of alpha-tropomyosin and the gene of p rotein C linked to cardiac myosin. The main problem for clinicians is not m aking the diagnosis, which is relatively simple by echocardiography, but to assess the risk of complications, especially in adolescents and young adul ts, Patients over 40 to 45 years of age pose fewer problems as their diseas e is generally associated with a better prognosis since they have already s urvived to that age. There are many prognostic factors of sudden death, a r eflection of the multifactorial character of sudden death in this disease. Four major risk factors have been identified : a family history of sudden d eath, abnormal blood pressure changes on exercise, a history of syncope and non-sustained ventricular tachycardia on 24 or 48-hour Holter monitoring. In children and adolescents, only the first three factors may be used, know ing that syncope, though rare, carries a very poor,prognosis. On the other hand, in adults up to 40, all 4 factors are valid. Unfortunately their posi tive predictive value is relatively poor, all the patients with one of thes e risk factors not automatically experiencing sudden death. On the other ha nd, their negative predictive value is excellent. Therefore, a patient with none of these factors has an excellent prognosis and should be allowed to lead a normal life. The risk is considered to be high when 2 or 3 of the fa ctors are associated, theoretically justifying aggressive management (amiod arone ? defibrillator ?). Finally, there is no established management proto col in cases with a single risk factor. The discovery of mutations causing HCM will probably open up new methods of assessing the risk of sudden death in this disease. It would seem to be, possible to assess the impact of the genotype on prognosis. However, this "genetic stratiftcation" remains the realm of top research teams and is not yet accessible routinely in clinical practice.