Association of the Fourth Heart Sound With Increased Left Ventricular End-Diastolic Stiffness

Abstract Background Although the fourth heart sound (S4 ) is thought to be associated with a stiff left ventricle, this association has never been proven. Recently, single-beat estimation of the end-diastolic pressure volume relationship (EDPVR) has been characterized (P = αVβ ), allowing the estimation of EDPVR in larger groups of patients. We hypothesized that the S4 is associated with an upward- and leftward-shifted EDPVR, indicative of elevated end-diastolic stiffness. Methods and Results Ninety study participants underwent acoustic cardiographic analysis, echocardiography, and left heart catheterization. We calculated α and β coefficients to define the nonlinear slope of the EDPVR using the single-beat method for measuring left ventricular end-diastolic elastance. In the P = αVβ EDPVR estimation, α was similar ( P = .31), but β was significantly higher in the S4 group (5.96 versus 6.51, P = .002), signifying a steeper, upward- and leftward-shifted EDPVR curve in subjects with an S4 . The intensity of the S4 was associated with both β ( r = 0.42, P < .0001) and E/E′ ÷ stroke volume index, another index of diastolic stiffness ( r = 0.39, P = .0008). On multivariable analysis, β remained associated with the presence ( P = .008) and intensity ( P < .0001) of S4 after controlling for age, sex, and ejection fraction. Conclusions The S4 is most likely generated from an abnormally stiff left ventricle, supporting the concept that the S4 is a pathologic finding in older patients.