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

J Card Fail. 2008 Jun;14(5):431-6. doi: 10.1016/j.cardfail.2008.01.010. Epub 2008 May 27.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustics
  • Aged
  • Aged, 80 and over
  • Cross-Sectional Studies
  • Diastole
  • Female
  • Heart Sounds*
  • Heart Ventricles / physiopathology
  • Hemodynamics
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Phonocardiography
  • Stroke Volume
  • Ultrasonography
  • Ventricular Dysfunction, Left / diagnostic imaging
  • Ventricular Dysfunction, Left / physiopathology*