Third heart sound in health and disease

Third heart sound in health and disease

Third heart sound (S3) occurs in early diastole due to rapid deceleration of transmitral blood flow as the ventricles fill [1]. It corresponds in timing to shortly after the peak of the early diastolic E wave of transmitral flow. S3 occurs just after the opening of the atrioventricular valve as blood filling the atria during ventricular systole flows quickly into the ventricles [2].

Third heart sound can occur under physiological conditions as well as in disease, though not heard in all individuals. A prospective study of 580 patients had isolated valvular mitral regurgitation in 299, aortic regurgitation in 121 and primary left ventricular dysfunction with or without functional mitral regurgitation in 160 [3]. Association between audible S3 noted in routine clinical practice by internal medicine physicians and hemodynamic alterations measured by Doppler echocardiography was checked. S3 was more often heard in patients with primary left ventricular dysfunction (46%), compared to mitral (16%) or aortic regurgitation (12%). Patients with S3 were more likely to have class III-IV symptoms and higher mean pulmonary arterial pressures. It was a marker of severe regurgitation in all patient groups, with highest odds ratio in mitral regurgitation. While S3 was associated with marked dilatation in mitral regurgitation, it was associated with ejection fraction <50% in aortic regurgitation.

Physiological S3 is because of rapid early diastolic ventricular filling. In younger individuals atrial contraction contributes to only about 15% of ventricular filling while in older persons with left ventricular diastolic dysfunction, this may be 35-40% [2]. Hence a physiological S3 which may be heard in young persons disappears as age increases when early diastolic left ventricular filling decreases proportionally. Physiological S3 may be heard in pregnancy as there is enhanced intravascular volume.

In mitral regurgitation S3 need not indicate left ventricular dysfunction, though the prevalence increases with increasing severity of mitral regurgitation [4]. Left ventricular ejection fraction was lower when S3 was detected in patients with aortic stenosis or a combination of aortic stenosis and regurgitation. In mitral regurgitation, three mechanisms can produce S3. They are augmented early diastolic filling, increased stroke volume and also left ventricular systolic dysfunction when present. S3 was heard in 46% of cases with mitral regurgitation in the study. The frequency increased with increasing severity of mitral regurgitation, independent of left ventricular ejection fraction.

In another study, 90 patients underwent phonocardiography, echocardiography with tissue Doppler imaging and left heart catheterization [5]. S3 was detected in 21 patients (23%). Those with S3 had a lower left ventricular ejection fraction, increased deceleration slope of mitral inflow E wave, elevated E/E’ ratio from tissue Doppler of mitral annulus and elevated left heart filling pressures on left heart catheterization.


  1. Manson AL, Nudelman SP, Hagley MT, Hall AF, Kovács SJ. Relationship of the third heart sound to transmitral flow velocity deceleration. Circulation. 1995 Aug 1;92(3):388-94.
  2. Wynne J. The clinical meaning of the third heart sound. Am J Med. 2001 Aug;111(2):157-8.
  3. Tribouilloy CM, Enriquez-Sarano M, Mohty D, Horn RA, Bailey KR, Seward JB, Weissler AM, Tajik AJ. Pathophysiologic determinants of third heart sounds: a prospective clinical and Doppler echocardiographic study. Am J Med. 2001 Aug;111(2):96-102.
  4. Folland ED, Kriegel BJ, Henderson WG, Hammermeister KE, Sethi GK. Implications of third heart sounds in patients with valvular heart disease. The Veterans Affairs Cooperative Study on Valvular Heart Disease. N Engl J Med. 1992 Aug 13;327(7):458-62.
  5. Shah SJ, Marcus GM, Gerber IL, McKeown BH, Vessey JC, Jordan MV, Huddleston M, Foster E, Chatterjee K, Michaels AD. Physiology of the third heart sound: novel insights from tissue Doppler imaging. J Am Soc Echocardiogr. 2008 Apr;21(4):394-400.