Association of the fourth heart sound with increased left ventricular end-diastolic stiffness

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.

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.

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.