Clinical and Pathological Impact of Tissue Fibrosis on Lethal Arrhythmic Events in Hypertrophic Cardiomyopathy Patients With Impaired Systolic Function.

Abstract

The natural history of hypertrophic cardiomyopathy (HCM) varies from an asymptomatic benign course to a poor prognosis. Myocardial fibrosis may play a critical role in ventricular tachyarrhythmias (VT/VF); however, the clinical significance of tissue fibrosis by right ventricular (RV) biopsy in the long-term prognosis of HCM patients remains unclear. We enrolled 185 HCM patients (mean age, 57±14 years). The amount of fibrosis (%area) was quantified using a digital microscope. Hemodynamic, echocardiographic, and electrophysiologic parameters were also evaluated. Patients with severe fibrosis had longer QRS duration and positive late potential (LP) on signal-averaged ECG, resulting in a higher incidence of VT/VF. At the 5±4 year follow-up, VT/VF occurred in 31 (17%) patients. Multivariate Cox regression analysis revealed that tissue fibrosis (hazard ratio (HR): 1.65; P=0.003 per 10% increase), lower left ventricular ejection fraction (HR: 0.64; P=0.001 per 10% increase), and positive SAECG (HR: 3.14; P=0.04) led to a greater risk of VT/VF. The combination of tissue fibrosis severity and lower left ventricular ejection fraction could be used to stratify the risk of lethal arrhythmic events in HCM patients. Myocardial fibrosis in RV biopsy samples may contribute to abnormal conduction delay and spontaneous VT/VF, leading to a poor prognosis in HCM patients.