Biphasic force-frequency relation predicts primary cardiac events in patients with hypertrophic cardiomyopathy

Background: The force-frequency relation (FFR) is a hemodynamic index of the chronotropic relationship between left ventricular (LV) systolic function (percent change in dP/dt_max) and elevation of heart rate. FFR is a marker of myocardial contractile reserve and follows an upward slope in healthy myocardium [monophasic FFR (MoF)], a pattern that becomes biphasic (BiF) under pathological conditions. However, it remains uncertain whether the FFR determines a patient’s prognosis. We investigated the promising role of the FFR as a predictor of cardiac events in the setting of hypertrophic cardiomyopathy (HCM). Methods and Results: A total of 113 consecutive patients with HCM (New York Heart Association (NYHA) class I–II) were retrospectively evaluated; 27 (23.9%) had a BiF pattern and they experienced a higher incidence of cardiac events compared with those showing an MoF pattern (median follow-up, 4.7 years; P<0.001). Furthermore, Cox proportional hazard regression analysis revealed that the LV end-diastolic volume index (hazard ratio: 1.051, P=0.014) and BiF pattern (hazard ratio: 15.260, P=0.001) were independent predictors of primary cardiac events. Interestingly, abnormal reductions in myocardial regulatory molecules related to contractility (SERCA2α) were observed exclusively in the patients exhibiting a BiF pattern. Conclusions: The FFR reflects latent myocardial abnormalities and predicts cardiac events in the setting of HCM, even during the asymptomatic stages of the disease.