Familial hypertrophic cardiomyopathy. Cardiac ultrasonic abnormalities in genetically affected subjects without echocardiographic evidence of left ventricular hypertrophy

Aims It is not known whether the apparent normality of echocardiographicexamination results, in subjects bearing a mutation for hypertrophiccardiomyopathy but without ultrasonic left ventricular hypertrophy,is due to incomplete phenotypic expression, or inaccurate echocardiographiccriteria. The aim of this study was to search for echocardiographicabnormalities in these patients. Methods and Results Echocardiography was performed in 100 subjects from two familieswith a mutation in the ß-MHC (720) or My-BPC (714)genes. We compared genetically affected subjects with an apparentlynormal left ventricle (thickness <13mm) (20 patients), andnon-affected first-degree relatives (61 normal subjects). (1)Patients had a thicker left ventricular wall (9·7±1·4vs 8·9±1·4mm, P=0·03), a greaterindexed mass (107±18 vs 97±17g.m^–2, P=0·03),a larger left atrium (27±9 vs 23±10mm³, P=0·09)and lower wall stress (78±11 vs 89±15 10³dynes.cm^–2,P=0·002); these differences were highly significant afteradjustment for height, age and systolic blood pressure eitherfor wall thickness (P=0·073503), mass (P=0·005)or atrial volume (P=0·001), and the ventricular systolicdimension appeared smaller (P=0·01); (2) results remainedsignificant (P<0·01) when a lower cut-off value (11mm)or only adults (18 years) were considered; (3) a subanalysisof Family 714 (13 patients, 25 normals matched for sex, ageand height) showed the same trends. Conclusion In familial hypertrophic cardiomyopathy, genetically affectedsubjects with an apparently normal heart by echocardiographyshow slight ultrasonic structural and functional left ventricularmodifications, suggesting that the phenotype of the diseaseis a continuous spectrum from normal structure to typical hypertrophy.