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 = 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.

Conflict of interest statement

Potential conflicts of interest: None.

Figures

Figure 1. Methods for Estimating Left Ventricular End-Diastolic Stiffness

LV = left ventricular, EDPVR = end-diastolic pressure volume relationship, EDP = end-diastolic pressure, SV = stroke volume, EDV = end-diastolic volume. The slope of the EDPVR relationship can be estimated by the single-beat method (EDP=αEDVβ), EDP/SV, E/E’ (as a surrogate of EDP; see text) / SV, and EDP/EDV.

Figure 2. Differences in Left Ventricular Filling Pressures in Diastole – No S4 vs. S4

LV = left ventricle, EDP = end-diastolic pressure. Pressures in subjects with an S4 were higher from mid-to-end diastole. * = P<0.05; † = P<0.005

Figure 3. Differences in Left Ventricular End-Diastolic Pressure-Volume Relationship – No S4 vs. S4

EDV20 = group-averaged end-diastolic volume at left ventricular end-diastolic pressure of 20 mmHg. Patients with an S4 had an upward and leftward-shifted end-diastolic pressure volume relationship (signifying increased end-diastolic stiffness), as shown by the decreased group-averaged EDV20 in the S4 group.