Biphasic Force-Frequency Relation Predicts Primary Cardiac Events in Patients With Hypertrophic Cardiomyopathy

Abstract

Background:The force-frequency relation (FFR) is a hemodynamic index of the chronotropic relationship between left ventricular (LV) systolic function (percent change in dP/dtmax) 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.

Left ventricular contractile reserve in stress echocardiography: the bright side of the force

“…The technique remained strictly confined to the academic context for decades [35][36][37]. Nevertheless, in selected populations submitted to laborious studies, the force evaluated with invasive methods clearly separated hypertrophic cardiomyopathy patients with steep force-frequency relationship and good prognosis from those with flat or biphasic relationship and bad prognosis [38]. This elegant pathophysiological concept was never applied in a clinically realistic non-invasive environment.…”

The Expanding Role of Stress Echocardio­graphy in Hypertrophic Cardiomyopathy

“…A small molecule, MYK-461, reduces contractility by decreasing the adenosine triphosphatase activity of the myosin heavy chain. The early, chronic administration of MYK-461 suppresses the development of left ventricular hypertrophy, cardithat hyperdynamic contraction is essential for HCM pathobiology (24). The possibility of incorporating a simple and reproducible biomarker of LV contractility such as force in the SE assessment of HCM seems especially attractive as new molecular therapies of contractility are now being tested in clinical studies.…”