Letter by Geier et al Regarding Article, “Hypertrophic Cardiomyopathy Is Predominantly a Disease of Left Ventricular Outflow Tract Obstruction”
To the Editor:
We read with great interest the article by Maron et al1 reporting hypertrophic cardiomyopathy (HCM) as a predominantly obstructive disease. The authors describe in their carefully conducted study a cohort of 320 patients, 70% of whom present with either resting or provocable obstruction of the left ventricular outflow tract.
Our own data from a cohort of 186 unrelated HCM patients confirm that distribution: 65% of our patients presented with significant left ventricular outflow tract gradient either at rest or on exercise.2 We assume that the patients examined by Maron et al were also familially unrelated. However, HCM is an autosomal dominant heritable disorder with a 50% chance of transmission to the offspring. To make a reliable estimation for the prevalence of obstruction in HCM, it would be reasonable to also include other affected family members into this estimation. The wide spectrum of clinical expression is a well-known phenomenon of HCM and is sometimes particularly striking within families. Frequently, clinical signs in other family members who have inherited the disease-causing mutation are hard to detect and require intensive clinical scrutiny. Many affected relatives are asymptomatic, which can obscure the heritable nature of HCM in such families. Thus, the clinical presentation in affected relatives may be confined to ECG-specific signs of hypertrophy or to tissue Doppler abnormalities in the absence of overt hypertrophy.3 This has been incorporated into a set of modified criteria for diagnosis of HCM in immediate relatives.4
In HCM referral centers (like those from the authors), however, there is a strong selection bias for severely affected patients. Therefore, there may be differences between the general HCM population and the HCM cohort of a tertiary referral center. Often patients are referred to specialized centers for further evaluation either when they are symptomatic or when a conspicuous heart murmur has been detected, both of which are predictors of an obstructive form of HCM. It should therefore be considered that the actual prevalence of left ventricular outflow tract obstruction in the general HCM population, as seen in smaller hospitals and outpatient clinics, may be lower than the proportion described by Maron et al.
Maron MS, Olivotto I, Zenovich AG, Link MS, Pandian NG, Kuvin JT, Nistri S, Cecchi F, Udelson JE, Maron BJ. Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction. Circulation. 2006; 114: 2232–2239.
Kabaeva ZT, Perrot A, Wolter B, Dietz R, Cardim N, Correia JM, Schulte HD, Aldashev AA, Mirrakhimov MM, Osterziel KJ. Systematic analysis of the regulatory and essential myosin light chain genes: genetic variants and mutations in hypertrophic cardiomyopathy. Eur J Hum Genet. 2002; 10: 741–748.
Geier C, Perrot A, Özcelik C, Binner P, Counsell D, Hoffmann K, Pilz B, Martiniak Y, Gehmlich K, van der Ven PF, Fürst DO, Vornwald A, von Hodenberg E, Nürnberg P, Scheffold T, Dietz R, Osterziel KJ. Mutations in the human muscle LIM protein gene in families with hypertrophic cardiomyopathy. Circulation. 2003; 107: 1390–1395.
McKenna WJ, Spirito P, Desnos M, Dubourg O, Komajda M. Experience from clinical genetics in hypertrophic cardiomyopathy: proposal for new diagnostic criteria in adult members of affected families. Heart. 1997; 77: 130–132.