Abstract 2161: Left Ventricular Dysfunction and Outcome in Myofilament Positive and Myofilament Negative Hypertrophic Cardiomyopathy
Background. Mutations in sarcomere myofilament protein genes represent the most prevalent cause of hypertrophic cardiomyopathy (HCM). A collective clinical characterization of myofilament positive (as opposed to negative) HCM has not been previously attempted.
Methods. A cohort of 203 unrelated patients with HCM (age 50±18 years, 36% female) was followed for 4.0±1.7 years following mutational analysis of MYBPC3 (myosin binding protein C), MYH7 (beta-myosin heavy chain), MYL2 and MYL3 (regulatory and essential light chains), TNNT2 (troponin T), TNNI3 (troponin I), TPM1 (alpha-tropomyosin), and ACTC (alpha actin) by DHPLC and automatic DNA sequencing.
Results. Eighty-seven mutations were identified in 126 myofilament positive HCM patients (62%). Compared to myofilament negative (n=77), patients with myofilament-HCM were younger at diagnosis (41 vs. 46 years; p=0.06), and more often had family history of HCM (36% vs. 17%, p<0.01) or sudden death (18% vs. 8%, p<0.01). Patients with myofilament-HCM showed greater life-time probability of developing systolic dysfunction (LVEF<50%) and restrictive LV filling (transmitral E/A >1.5 and deceleration time <140 ms), irrespective of the myofilament involved. Prospectively, myofilament positive status was associated with a 4.27 independent relative risk of cardiovascular death, non-fatal stroke or progression to NYHA class III/IV (95% confidence interval 1.46–12.48, p=0.0079). The endpoint occurred at a wide age range in myofilament positive patients (14–86 years), but only ≥65 years in myofilament negative.
Conclusions. Myofilament-HCM was associated with greater prevalence of LV dysfunction and adverse prognosis compared to myofilament negative disease, irrespective of the myofilament (thick, intermediate, or thin) involved. These findings for the first time demonstrate a potential clinical and prognostic role of sarcomeric genetic testing in patients with HCM.