Download Abnormal Left Ventricular Relaxation in Hypertensive Patients

CIinicalScience(1980) 59,411s414s
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Abnormal left ventricular relaxation in hypertensive patients
F. M . F O U A D , R. C . T A R A Z I , J . H . G A L L A G H E R , * W. J . MACI NTYRET
A N D S . A. C O O K ?
Research Division, *Division of Radiology, and tNuclear Medicine Department. Cleveland Clinic Foundation, Cleveland,
Ohio, U S A .
Summary
1. The maximum rates of left ventricular
ejection and filling were derived (Fourier analysis)
from the left ventricular volume curve Cgrn
technetium-human serum albumin gated blood
pool studies) in 12 normotensive subjects and 15
hypertensive patients of matched age groups.
2. Average values of cardiac output, ejection
fraction, heart rate and left ventricular ejection
rate were not significantly different in the two
groups.
3. Hypertensive patients had a slower rate of
left ventricular filling (P < O.OS), suggesting
diminished left ventricular compliance in hypertension.
Key words: ejection fraction, filling rate, hypertension, radionuclide.
Introduction
In contrast with the many investigationsrelated to
cardiac systole (Braunwald, Ross & Sonnenblick, 1976), the relaxation and filling of the heart
have been little studied (Grossman & McLaurin,
1976). In response to the increased pressure load,
the performance of the myocardium has been
variously described as normal, increased or
reduced (Burton, 1957; Downing & Sonnenblick,
1964; Wilcken, Charlier, Hoffman & Guz, 1964;
Sagawa, 1967). However, filling and relaxation
rates of the left ventricle in hypertension have not
yet been investigated in any detail. The development of radionuclide techniques has allowed the
inscription of ventricular volume curves in man
by minimally invasive means (Pitt & Strauss,
1977). A single descriptive study of a heteroCorrespondence: Dr Fetnat M. Fouad, Research
Division, Cleveland Clinic Foundation, 9500 Euclid
Avenue, Cleveland, Ohio 44106, U.S.A.
geneous group of patients suggested that the
velocity of left ventricular filling appeared to be
reduced among hypertensive patients (Qureshi,
Wagner, Alderson, Housholder, Douglas,
Lotter, Nickoloff, Tanabe & Knowles, 1978).
The present study was therefore designed to
determine left ventricular ejection and filling rates
in hypertensive patients.
Materials and methods
Twelve normotensive subjects with no clinical or
electrocardiographic evidence of heart disease
volunteered for the study. A group of 15
untreated patients with essential hypertension was
investigated concurrently. Age range was the
same for both groups (20-66 years). All gave
their informed consent. The doses of radionuclides used were approved by the Radioisotope Safety Committee and the Institutional
Review Committee.
Left ventricular volume curves were obtained
from gated blood pool studies (Pitt & Strauss,
1977) after intravenous injection of 12 mCi of 99m
technetium4uman serum albumin. All studies
were performed in the morning with subject at
rest in the supine position. Cardiac output was
obtained from the same radionuclide during its
first-pass flow (Fouad, Tarazi, MacIntyre &
Durant, 1979). Simultaneously, blood pressure
and heart rate were recorded and derived data
calculated (Tarazi, Ibrahim, Dustan & Ferrario,
1974).
Analysis of left ventricular volume curves: left
ventricular (LV)ejection fraction was calculated
as (LV end-diastolic counts - LV end-systolic
counts) LV end-diastolic counts.
Rates of ejection and filling: Fourier analysis
(Geffers, Adam, Bitter, %gel& Kampmann, 1978)
was applied to fit a curve to the data points (16 in
our system) by the method of least squares; the
time derivative of the curve was computed by
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F. M . Fouad et al.
using the Fourier transform technique as a global
estimate of the tangent to the curve at each data
point. Since this curve represents the radioactivity counts as a mathematical function of
time, the derivatives are expressed in C.P.S. The
negative derivatives correspond to the decrease in
counts or ejection phase (-dvldt) and the positive
derivatives correspond to the increase in counts or
filling phase (+dv/dt). In this analysis we looked
at the largest negative and maximum positive
derivatives. These derivatives were sealed by the
maximum absolute counts equivalent to the
end-diastolic counts to compensate for variation
in injected dose and efficiency of the acquisition
system. In this way it was possible to compare
data from different patients. The units of these
new variables are therefore expressed in units of
fractional change per second or Hertz and are
proportional to the change in volume per unit
time (dvldt).
Results
The two groups of subjects did not differ
significantly with respect to cardiac output,
ejection fraction of heart rate [3.05 & 0.18 vs
3.01 & 0.19 litres min-' m 2 , 0.52 & 0.01 vs
0.55 k 0 . 0 2 ' o r 62 & 2.50 vs 65 ? 3.18
beatshin, for normotensive and hypertensive
subjects respectively; P: not significant (N.S.) for
all]. The velocity of ventricular ejection (maximum -dv/dt) was not significantly different in
normotensive and hypertensive subjects (2.27 k
0.98 vs 2.48 0.16; P:N.S.); its correlation with
the ejection fraction was not significant in either
group (I = 0.39, P N.S. in normotensive subjects
and r = 0.12, P N.S. in hypertensive patients).
In contrast with these similarities between
normotensive and hypertensive subjects, the two
groups differed significantly in respect to the
maximum rate of left ventricular filling (maximum +dv/df). The filling rate was significantly
slower in hypertensive patients than in normotensive subjects (Fig. 1); the two groups could be
distinctly separated by linear discriminant
analysis (Lachenbruch, 1975). Also, the slopes of
the regression equations relating maximum +dv/
dt to maximum -dv/dt, in either group, were
significantly different (P< 0.05). It is to be noted
that data for four of the hypertensive patients fell
in a grey zone; study of their haemodynamic data
showed that they differed from other hypertensive patients in the group by a higher cardiac
index (> 3.6 litres min-' m-*) and shorter mean
transit time (< 7 s) indicative of hyperkinetic
circulations. Therefore they were considered
separately in the analysis of slopes. In both
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Max. ejection velocity (-duldr)
FIG. 1. Correlation of maximum rates of left ventricular ejection (-duldf) and of left ventricular filling
(+du/dt) in 12 normotensive subects (0;r 0.63, P <
0.05),11 essential hypertensive patients (0;r 0.56, P
< 0.05) and four hypertensive patients with hyperkinetic circulation (A).Patients with essential hypertension
had a slower rate of filling than norrnotensive subjects;
the difference between slopes was significant (P <
0.05) whereas that between intercepts was not. The
broken line illustrates the clear separation between the
two groups based on linear discriminant analysis.
groups, the maximum +dv/dt did not correlate
with heart rate, stroke volume or ejection fraction. As regards blood pressure, the alteration in
ventricular filling did not correlate with either
mean arterial pressure or systolic blood pressure
within the hypertensive and the normotensive
groups. For all subjects considered as a group,
there was a significant negative correlation
between mean arterial pressure and maximum
filling rate (I = -0-622, P < 0.001) after
exclusion of the four hyperkinetic hypertensive
patients (their inclusion lowered the r value to
-0.328, P > 0.05).
Discussion
Our results suggest that patients with hypertension frequently show a reduced rate of left
ventricular filling even in the absence of other
signs of cardiac involvement. Only two of our 15
patients had electrocardiographic evidence of left
ventricular hypertrophy; the average cardiac
output, heart rate and ejection fraction were not
significantly different between the normotensive
and hypertensive patients although the maximum
+dvldt was significantly reduced in the latter.
The left ventricle has frequently been assumed
to become less compliant than normal in
Left ventricularjlting rate in hypertension
conditions associated with increased pressure
load (Grossman, McLaurin & Rolett, 1979). This
diminished compliance was attributed to the
increased muscle mass andlor increased content
of interstitial and connective tissue in the left
ventricular wall. Most studies of left ventricular
compliance, however, were obtained from
patients with either aortic stenosis or cardiomyopathy (Sutton, Tajik, Gibson, Brown, Seward
& Giuliani, 1977; Sanderson, Traill, Sutton,
Brown, Gibson & Goodwin, 1978; Grossman et
al., 1979; Nesje & Enge, 1979). Very few data
were reported from hypertensive patients. Our
results confirm initial impressions of reduced
compliance, inasmuch as the reduction in
maximum filling rate of the ventricle can be
related to a reduced yielding of the left ventricle to
the inrushing blood from the left atrium. Further,
our results are also in agreement with other
studies showing that left atrial hypertrophy can
occur very early in hypertension and constitute
the sole sign of cardiac involvement (Tarazi,
Miller, Frohlich & Dustan, 1966). This atrial
abnormality was interpreted as reflecting reduced
compliance of the left ventricle (Gibson, Madry,
Grossman, McLaurin & Craig, 1974). Somewhat
unexpected, however, was the finding that this
reduction in rate of left ventricular filling could be
the earliest demonstrable disturbance in cardiac
function. More precise estimates of left ventricular wall thickness by echocardiography are
needed to correlate left ventricular wall thickness
with changes in ejection and filling velocity since
the echocardiogram is more sensitive than
electrocardiographic studies in determining the
structural conditions of the left ventricular wall.
The factors associated with the reduced rate of
filling could not be determined from this study;
neither heart rate nor stroke volume nor ejection
fraction correlated with the rate of ejection or
filling of the heart. Parmley & Sonnenblick (1969)
have reported a reduced relaxation rate of
isolated papillary muscles in response to isoprenaline stimulation. Recent studies have confirmed
this abnormality in the hypertrophied hearts of
spontaneously hypertensive rats (Saragoca &
Tarazi, 1980). There was, however, no particular
evidence of sympathetic hyperactivity in our
group of patients. Further, in the absence of direct
measurements of left ventricular diastolic pressure, it is difficult to speculate on alterations in
ventricular compliance. Nevertheless, our studies
point to a long neglected yet potentially important
pathophysiological disturbance of cardiac relaxation in hypertension, which may play an important role in the mosaic of factors determining its
evolution. Thoren (1979) has reported significant
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alterations in atrial and ventricular reflexes
secondary to a reduction of left ventricular
compliance in hypertensive animals.
We did not find a significant correlation
between mean arterial pressure (or systolic blood
pressure) and +dv/dt either among normotensive
subjects or among the 15 hypertensive patients.
Studies of larger groups, particularly in response
to blood pressure variations, are obviously needed
to differentiate functional and structural components in the reduced rate of left ventricular
filling.
Acknowledgments
We thank Mr Bruno Sufka for computer programming, Carmen Napoli, Steve Saverna and
Mary Kay Kruchan for technical assistance, and
Aldona Raulinaitis and Susan Bir for secretarial
assistance. Statistical analysis was accomplished
by using PROPHET, a national computer
resource supported by the Biotechnology
Resources Program, Division of Research
Resources, National Institutes of Health. The
studies were supported in part by a grant from the
National Heart, Lung and Blood Institute (HL6835).
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