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

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 = αV^β), 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 = αV^β 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.