1718
JACC Vol. 14, No. 7
December 1989:171&20
Editorial Comment
Insights Into the Physiologic
Significance of the Mitral Inflow
Velocity Pattern*
ROBERT A. LEVINE,
JAMES D. THOMAS,
Boston,
MD, FACC,
MD, FACC
Massachusetts
The ability to measure mitral inflow velocities by Doppler
echocardiography has allowed us to examine left ventricular
filling noninvasively (1,2). Initially, the availability of this
information generated great enthusiasm for extracting intrinsic diastolic properties of the left ventricle from a simple
analysis of these velocities, in particular, the early and late
diastolic filling velocities (the E and A waves) and their ratio.
This initial enthusiasm has been tempered by the growing
realization that inflow patterns result from a complex amalgam of ventricular, atria1 and mitral valve properties and are
profoundly influenced by superimposed loading conditions
(3-5). Because of these multiple determinants, similar mitral
inflow patterns could appear in different clinical settings if
the time course of the transmitral pressure gradient is similar
in those conditions.
The hypertrophic pattern versus decreased preload. One
of the earliest characteristic abnormal patterns described
(6-8) was the diminished early filling (E) wave and decreased
E/A wave ratio in patients with hypertrophic cardiomyopathy. These findings were explained by delayed ventricular
relaxation causing relatively high early diastolic left ventricular pressures and, therefore, a relatively low early diastolic
gradient across the mitral valve. More recently, however, a
similar pattern has been reproduced simply by decreasing
left-sided filling pressures without intrinsic myocardial
changes, for example, by nitroglycerin infusion: the de-
*Editorials published in Journal of the American College of Cardiolog
reflect the views of the authors and do not necessarily represent the views of
JACC or the American College of Cardiology.
From the Noninvasive Cardiac Laboratory, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts. Dr. Levine is a Clinician-Scientist of the American Heart Association,
with funds contributed by its Massachusetts Affiliate. This study was supported in part by Grant-in-Aid 13-532-867 from the American Heart Association, Massachusetts Affiliate, Inc., Boston, Massachusetts (Dr. Thomas); by
Grant HL-38176from the National Institutes of Health, Bethesda, Maryland;
and grants from the Whitaker Foundation, Mechanicsburg, Pennsylvania and
the American Heart Association, Dallas, Texas (Dr. Levine).
Address for renrints: Robert A. Levine, MD, Cardiac Ultrasound Laboratory, Phillips House 8, Massachusetts General Hospital, Boston, Massachusetts 02114.
01989 by the American College of Cardiology
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creased left atria1 pressure lowers the early diastolic gradient
and the corresponding E wave velocity (29-12). Conversely, the classic pattern in hypertrophic cardiomyopathy
can be masked by associated mitral regurgitation, which
raises left atria1 pressure (7).
The restrictive pattern. Another distinctive filling pattern
has been observed in restrictive cardiomyopathy (13-15).
The early filling wave rapidly decelerates from its peak as
left ventricular pressure rises rapidly in early diastole, and
the late filling (A) wave is variably reduced, presumably by
the high diastolic ventricular pressures. The E/A wave ratio
is consequently increased, and the elevated ventricular
pressures cause late diastolic mitral regurgitation in some
patients.
The effect of severe aortic regurgitation. This restrictive
pattern is mimicked by that now described by Oh et al. (16)
in this issue of the Journal in severe aortic insufficiency of
relatively acute onset. In 11 patients with this condition, the
early filling velocity was higher than in matched normal
control subjects and decelerated more rapidly from its peak;
the late filling wave tended to be smaller, and the E/A wave
ratio was abnormally high-changes that could be reversed
by surgical repair. Late diastolic mitral regurgitation also
occurred in 8 of the 11 patients.
Understanding these results in aortic regurgitation. Our
understanding of these findings is improved by relating them
to the fundamental determinants of transmitral flow. We
have described (3,4) a mathematical model of ventricular
filling that uses atria1 compliance, ventricular compliance
and relaxation, and mitral valve morphology to predict the
time course of atria1 and ventricular pressure and mitral
velocity. The effect of aortic regurgitation can be studied by
including aortic pressure and regurgitant orifice area in this
model (giving five coupled nonlinear differential equations
that must be solved simultaneously). The advantage of such
analysis is that it allows us to isolate primary causes from
secondary effects on the transmitral velocity pattern. For
instance, Figure 1A shows the isolated effect of increasing
aortic regurgitant orifice area with all other parameters held
at roughly physiologic values (mitral area = 4 cm2, exponential pressure-volume curves for the atrium and ventricle,
ventricular relaxation time constant = 40 ms, initial left atria1
pressure = 10 mm Hg, aortic pressure = 100 mm Hg). As the
aortic regurgitant orifice area increases from 0 to 0.6 cm2, the
early filling wave undergoes profound changes, with peak
velocity falling from 71 to 43 cm/s and deceleration time
shortening from 124 to 66 ms. These changes reflect the
rising ventricular pressure, which decreases the pressure
gradient across the mitral valve. The filling volume for this
portion of diastole falls from 37.4 to 15.7 cm’.
Thus, the isolated
effect of worsening
aortic regurgitation
0735.1097/89/$3.50
LEVlNE AND THOMAS
EDITORIAL COMMENT
JACC Vol. 14. No. 7
December lY89:1718-XI
Figure 1. Competing effects of worsening aortic regurgitation (AR) and left
atrial (LA) pressure on the configuration of the early mitral filling wave. A,
Enlarging the aortic regurgitant orifice
area (AROA) decreases peak E wave
velocity (E) and shortens deceleration
time (DT). B, For a 0.6 cm’ aortic
regurgitant orifice area, increasing left
atrial pressure (LAP) at the mitral
valve opening raises peak velocity dramatically (137%) with a relatively minor (24%) increase in deceleration
time. Note that the smallest curves in
the two graphs display the same data
(AROA = 0.6 cm’. LAP = IO mm Hg).
AT = acceleration time (ms): FV =
filling volume (trammitral flow during
E wave. cm’).
A
,20_+xi~y_ (cm/secl
Effect
100 -
80.
A
";?A
‘1”,’
71
E
104
&T 124
LT
37.4
E_V
0.2
;g
%
10
62
53
43
100
96
90
26.9
21.6
15.7
200
300
Time (msec)
time (as noted by Oh et al. [161)
and also to decrease peak velocity (in contrast to their
findings). However, the natural physiologic compensation
for this fall in filling volume is to raise left atria1 pressure to
preserve forward output (though at the expense of pulmonary congestion), the effect of which is shown in Figure IB.
All curves are for an aortic regurgitant orifice area of 0.6 cm2
with atria1 pressures of 10 to 25 mm Hg. Peak velocity rises
from 43 to 102 cm/s and filling volume from 15.7 back to the
original 37.5 cm3. The deceleration time remains short at 82
ms. Thus, this model of severe aortic regurgitation with
compensatory rise in atria1 pressure reproduces precisely the
findings of Oh et al. (16) concerning the E wave. Of course,
E wave velocities could also be increased by mitral regurgitation, which was present in systole in at least one patient
(Fig. 2 of that paper [16]) and just before systole in eight.
The late diastolic
of
A wave is not modeled here because the
atria1 systolic fitnction
are incompletely
However. we expect the A wave to depend on
both preload (atria1 pressure at the time of the A wave) and
afterload (ventricular pressure and compliance). High left
atria1 pressure should cause a more forceful contraction and
(if atria1 afterload is held constant) a larger A wave; in
contrast, a stiff ventricle should limit atria1 transmitral flow
for the same force of atria1 contraction. In the case of severe
aortic regurgitation, therefore, we can conclude that the
profoundly elevated end-diastolic ventricular pressures
more than offset any enhanced contractility from elevated
atrial pressures. The net result is thus to see tall, narrow E
waves and blunted A waves.
Clinical implications. As in the case of the mitral inflow
pattern seen in hypertrophic disease, these findings illustrate
that different clinical entities can generate similar alterations
in selected measures of the mitral inflow pattern, such as the
deceleration time of the E wave and the E/A wave ratio.
Therefore. these features of the inflow pattern must be
understood.
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.__
of Increasincl AR
is to shorten deceleration
determintrnts
1719
100
60
66
200
300
Time (msecl
interpreted in the context of atrial and ventricular loading
conditions.
The pattern described by Oh et al. (16), along with
findings such as proximal jet width (17,18) and the deceleration half-time of the aortic regurgitant jet (19). can serve as
corroborative evidence of severe aortic regurgitation. It
must be recognized that this mitral inflow velocity pattern,
like the aortic regurgitant half-time, depends on left ventricular compliance,
and is therefore most applicable with
regurgitation of acute onset, as in the patients studied. Over
time and with increasing compliance, diastolic ventricular
pressures should fall, causing mitral inflow velocities to
assume a more normal pattern. Similarly, Downes et al. (20)
described diastolic mitral regurgitation in a series of patients
with acute severe aortic regurgitation but not in a group with
chronic insufficiency, also severe. Further, as Oh et al. (16)
note. their findings were described in a group of patients
known to have severe aortic regurgitation by clinical assessment and correlative tests; broader application of these
findings will require further prospective study.
Finally. their results emphasize the need to study the
effects of aortic insufficiency and left ventricular compliance
on the Doppler pressure half-time method for assessing
stenotic mitral valve area. The dependence of the half-time
on factors other than mitral valve area has already been
demonstrated by the inaccuracies in this method immediately after percutaneous mitral valvotomy (2 I). The potential
of aortic insufficiency for decreasing the pressure half-time
and causing mitral valve area to be overestimated requires
further study as a function of the chronicity of the regurgitant lesion and ventricular compliance. in view of the
variable initial clinical results (22-25).
Conclusions. Similar Doppler mitral inflow velocity patterns can be produced by different conditions causing similar
changes in the time course of the transmitral pressure
difference. Nevertheless. informed interpretation of these
1720
LEVINE AND THOMAS
EDITORIAL COMMENT
patterns guided by the results of computational models and
in vitro simulations can allow us to extract meaningful
pathophysiologic insights from them.
We thank Arthur E. Weyman, MD for review of the manuscript.
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