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Natural History of Hypertrophic Cardiomyopathy in a Large Community-Based Population
Abstract & Commentary
Synopsis: Hypertrophic cardiomyopathy in the community is a benign disease associated a relatively low incidence of cardiac death. Syncope and left ventricular outflow tract obstructions are the 2 factors associated with sudden death or functional deterioration, respectively.
Source: Kofflard MJ, et al. J Am Coll Cardiol. 2003;41: 987-993.
This paper gives the natural history of hypertrophic cardiomyopathy in a large population of patients followed in Rotterdam, The Netherlands. Patients in this series were either diagnosed and treated at the center or were referred from the immediate community. A small group of self-referred family members are also included. The study population included 225 patients. Each patient was followed at yearly intervals after their initial examination. One hundred and thirteen patients were entered into the study between 1970 and 1990. One hundred and twelve patients were entered into the study after 1990. Noninvasive tests were performed as appropriate during the course of the study. Cardiac catheterization was performed only in patients with refractory symptoms or in preparation for surgery.
The majority of patients were male (58%). At the time of the first visit, 63 of the patients were younger than 30 years of age, and 20 were older than 65 years of age. The mean age of diagnosis was 37 ± 17 years. There was a positive family history of hypertrophic cardiomyopathy in about half of the patients, and there were 52 patients who reported sudden death in a first-degree relative. Angina (26%), dyspnea (36%), syncope (19%), and palpitations (19%) were the most common symptoms at presentation. Most of the patients had either no or minor functional impairment. At presentation, 100 patients were NYHA functional class I, 101 patients were class II, and 24 patients were class III. At echocardiography, the mean interventricular septal thickness was 21 ± 4 mm, and only 30 patients had marked left ventricular hypertrophy defined as a wall thickness greater than or equal to 25 mm. Left ventricular outflow tract obstruction was present at rest or was on provocation in 98 patients. At the time of the initial visit, 7 patients presented with persistent atrial fibrillation. Episodes of nonsustained ventricular tachycardia on a 24-hour ambulatory ECG monitor were noted in 73 of the 149 patients who had these recordings.
During follow-up, there were 44 deaths. Twenty-seven of these deaths were cardiovascular in nature, and 20 of these deaths were sudden. There were 17 deaths due to noncardiac causes. The annual mortality, annual cardiac mortality, and annual mortality due to sudden death were 1.3%, 0.8%, and 0.6%, respectively. The 5-, 10-, and 15-year cumulative cardiac survival in the entire group was 96%, 91%, and 78%, respectively. For comparison, the 15-year survival for an age map population would be about 90%. Marked left ventricular hypertrophy was not a specific marker for sudden death. Five of the patients with marked left ventricular hypertrophy died suddenly (16%) compared with 15 of 195 (7%) patients without marked hypertrophy. There was no difference in survival for patients with or without marked left ventricular hypertrophy. Deterioration in cardiac function was more commonly associated with left ventricular outflow tract obstruction (33% vs 7%). Left ventricular outflow tract obstruction, however, did not result in sudden death with 10% of the patients with obstruction and 8% of the patients without obstruction dying suddenly. Similarly, nonsustained ventricular tachycardia was not predictive of sudden death. Sudden cardiac death was observed in 8 of 73 patients with ventricular tachycardia (11%) and in 6 (8%) of the 76 patients without VT.
A multivariate analysis for prediction of sudden death was performed using the data in the trial. This showed that only syncope was a predictor for sudden cardiac death. Left ventricular outflow tract obstruction was an independent predictor for functional deterioration.
Kofflard and associates also reported a review of the literature on prognosis and hypertrophic cardiomyopathy. The data in the current series differ from those in reports, which were largely from referral centers. In those referral centers, patients tended to be younger, had more severe presentations or had more advanced functional impairment. The series from referral centers had a total cardiac mortality that was approximately twice that observed in this community-based series. Kofflard et al conclude that hypertrophic cardiomyopathy in the community is a benign disease associated a relatively low incidence of cardiac death. Syncope and left ventricular outflow tract obstructions are the 2 factors associated with sudden death or functional deterioration, respectively.
Comment by John DiMarco, MD, PhD
Hypertrophic cardiomyopathy is one of the most difficult problems with which cardiologists deal. There are a large number of mutations that result in hypertrophic cardiomyopathy. The natural history of each of these genotypes, however, has not been fully characterized. In most cases when patients present with hypertrophic cardiomyopathy, physicians do not have enough information from the family history in order to estimate their patient’s prognosis. The literature on hypertrophic cardiomyopathy often focuses on high-risk series from referral centers. As shown here, patients from referral centers may not represent the true natural history of the disease. Sudden death in hypertrophic cardiomyopathy often presents early in life. Factors associated with risk of sudden death in these young individuals have been nonsustained VT on monitoring, syncope, and significant left ventricular hypertrophy. However, older individuals tend to have a more benign course. In these patients, sudden death, when it occurs, happens in the setting of advanced heart failure and is usually preceded by functional deterioration. The latter patients are more commonly seen in a community setting.
The data from this community-based study by Kofflard et al are quite instructive. It will be helpful in guiding physicians who evaluate and care for individuals older than 30 with hypertrophic cardiomyopathy. It will remain problematic how to approach younger individuals. Clearly, if a family history of sudden death is available in these individuals, aggressive therapy should be pursued. Hopefully, in the future, a better knowledge of the genetic basis of hypertrophic cardiomyopathy and the ability to predict prognosis from knowledge of genotype will be used to guide therapy.
Dr. DiMarco is Professor of Medicine Division of Cardiology University of Virginia, Charlottesville.