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 = alphaV(beta)), allowing the estimation of EDPVR in larger groups of patients. We hypothesized that the S(4) 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 alpha and beta coefficients to define the nonlinear slope of the EDPVR using the single-beat method for measuring left ventricular end-diastolic elastance. In the P = alphaV(beta) EDPVR estimation, alpha was similar (P = .31), but beta was significantly higher in the S(4) group (5.96 versus 6.51, P = .002), signifying a steeper, upward- and leftward-shifted EDPVR curve in subjects with an S(4). The intensity of the S(4) was associated with both beta (r = 0.42, P < .0001) and E/E' / stroke volume index, another index of diastolic stiffness (r = 0.39, P = .0008). On multivariable analysis, beta remained associated with the presence (P = .008) and intensity (P < .0001) of S(4) after controlling for age, sex, and ejection fraction.
Conclusions: The S(4) is most likely generated from an abnormally stiff left ventricle, supporting the concept that the S(4) is a pathologic finding in older patients.