Third Heart Sound

Physiology of the Third Heart Sound: Novel Insights
from Tissue Doppler Imaging
Sanjiv J. Shah, MD, Gregory M. Marcus, MD, Ivor L. Gerber, MD,
Barry H. McKeown, MD, Joshua C. Vessey, MD, Mark V. Jordan, MD,
Michele Huddleston, RN, MS, Elyse Foster, MD, Kanu Chatterjee, MB, and
Andrew D. Michaels, MD, MAS, San Francisco, California; and Salt Lake City, Utah
Background: The third heart sound (S3) is thought to be caused by the abrupt deceleration of left ventricular
(LV) inflow during early diastole, increased LV filling pressures, and decreased LV compliance. We sought to
determine whether the ratio of early mitral inflow velocity to diastolic velocity of the mitral annulus (E/E’) could
confirm the proposed mechanism of the S3.
Methods: A total of 90 subjects underwent phonocardiography, echocardiography, tissue Doppler imaging,
and left-sided heart catheterization.
Results: Phonocardiography detected an S3 in 21 patients (23%). Subjects with an S3 had lower ejection
fraction (P .0006) and increased E deceleration rate (P .0001), E/E’ (P .0001) and filling pressures
(P .0001). The phonocardiographic S3 confidence score correlated with E/E’ (r 0.46; P .0001) and E
deceleration rate (r 0.43, P .0001). Of the echocardiographic variables, only E/E’ was independently
associated with the S3 confidence score (P .009), independently of invasively determined LV filling
pressures (P .001).
Conclusions: The most important determinants of the pathologic S3 are an increased deceleration rate of
early mitral inflow, elevated LV filling pressures, and abnormal compliance of the myocardium as measured
by tissue Doppler imaging.
The third heart sound (S3) is an important auscultatory finding with
diagnostic and prognostic value in a variety of clinical conditions,
including symptomatic and asymptomatic left ventricular (LV) dysfunction,
1-5 valvular heart disease,6,7 acute myocardial infarction,8
and noncardiac surgery.9 The S3 occurs in early diastole, approximately
120 to 160 msec after the second heart sound, during the
rapid LV filling phase10 and deceleration of early mitral inflow.11,12
Although it has limited sensitivity, the S3 has high specificity for the
detection of LV dysfunction.13
Since its initial description by Potain,14-16 there has been speculation
regarding the underlying physiology of the S3.8,17 It was previously
believed that the S3 resulted from transient mitral valve closure
in early diastole18,19 or impact of the heart against the chest wall.20
Most now agree that an abrupt limitation of LV inflow during early
diastole causes vibration of the entire cardiohemic system resulting in
the S3 under both physiologic and pathologic conditions.8,10,11,17 An
increase in the volume and pressure of mitral inflow in early diastole,
coupled with an abnormally stiff, noncompliant ventricle, is the ideal
setting in which the pathologic S3 becomes audible.17 These hemodynamic
conditions increase the deceleration rate of early mitral
inflow, a finding that has also been associated with the S3.12,21,22
Echocardiographic measurement of the ratio of mitral inflow
velocity to diastolic velocity of the mitral annulus (E/E’) with tissue
Doppler imaging (TDI) may be an ideal method to confirm the
proposed mechanism of the S3. However, there have been no known
prior studies on TDI and the S3.17
We hypothesized that the pathologic S3 is associated with an
elevated E/E’ and that mitral inflow and mitral annulus velocity may
be important characteristics underlying the physiology of the S3. We
therefore undertook a comprehensive investigation of the physiology
of the pathologic S3 using computerized phonocardiography, B-type
natriuretic peptide (BNP) testing, Doppler echocardiography, and
invasive LV hemodynamics in adult patients undergoing cardiac
catheterization.
METHODS
Study Participants
We performed a cross-sectional study of 100 unselected adult patients
referred for nonurgent cardiac catheterization at the University
of California, San Francisco Medical Center. The research protocol
From the Division of Cardiology, Department of Medicine, University of California,
San Francisco, California; and Division of Cardiology, Department of Medicine,
University of Utah, Salt Lake City, Utah.
Potential conflicts of interest: None.
Dr. Michaels received an unrestricted educational grant from Inovise Medical, Inc.
(Portland, OR). Dr. Shah is supported by a Heart Failure Society of America
Research Fellowship Award.
Reprint requests: Andrew D. Michaels, MD, MAS, Division of Cardiology, University
of Utah, 30 North 1900 East, Room 4A100, Salt Lake City, UT 84132-2401
(E-mail: andrew.michaels@hsc.utah.edu).
0894-7317/$34.00
Copyright 2008 by the American Society of Echocardiography.
doi:10.1016/j.echo.2007.06.007
394