Abstract 10181: Natural History of Genotype Positive Phenotype Negative Patients with Hypertrophic Cardiomyopathy
Background: Hypertrophic cardiomyopathy (HCM) is a clinically and genetically heterogeneous disease. Commercially available genetic testing has resulted in the emergence of a new subgroup of patients who carry the gene mutation but have no evidence of left ventricular (LV) hypertrophy, i.e. genotype positive phenotype negative (G+P-) individuals. This study sought to investigate the natural history of G+P- patients with HCM.
Methods: Patients attending the National HCM Center in Sydney, Australia, who carry a pathogenic gene mutation for HCM but without evidence of LV hypertrophy on 2D echocardiography were included in the study. A minimum of one year of follow-up was required. Clinical, ECG, and echocardiographic details were recorded. Patients were analysed in two groups, those aged less than or equal to 18 years and greater than 18 years at their first visit.
Results: A total of 32 G+P- HCM patients were included. The mean age at first visit was 22.7 years, with a female predominance (62%). A family history of sudden cardiac death was present in 69%, and 97% of patients were NYHA class I. The underlying mutations were identified in MYBPC3 (63%), MYH7 (19%), TNNI3 (4%) and ACTN2 (2%). One patient carried two mutations. During a mean follow-up period of 4.1 years, only one patient developed clinical HCM, a boy aged 7 years who developed LV hypertrophy by age 16 years and had an implantable cardioverter-defibrillator (ICD) for primary prevention. No patients developed new symptoms or had syncope. A small increase in LV wall thickness was observed in those aged less than or equal to 18 years (7.4 ± 1.8 to 8.9 ± 2.5 mm; p=0.02) consistent with normal physiological cardiac growth. No increase was observed in those aged greater 18 years (9.7 1.1 to 10.0 1.0 mm; p=0.50).
Conclusions: The vast majority of G+P- HCM patients did not develop any significant clinical disease. The G+P- state may represent a more benign form of HCM, particularly when a patient remains phenotype negative in adulthood. Further long-term prospective studies are required to characterise in more detail the natural history of G+P- patients with HCM.
- © 2011 by American Heart Association, Inc.