Circulation, Vol 77, 625-637, Copyright © 1988 by American Heart Association
KM Borow, RM Lang, A Neumann, JD Carroll and SI Rajfer
Clinical trials in patients with dilated cardiomyopathy (DCM) have shown a
wide disparity in the hemodynamic responses to positive inotropic therapy.
In addition, the response of the failing left ventricle to positive
inotropic agents reflects the net interaction of multiple factors,
including the magnitude of contractile abnormality and compensatory
mechanisms. In the current study, left ventricular geometry, loading
conditions, and contractile state were assessed in 13 patients with
nonischemic DCM with the use of simultaneous high- fidelity pressure
measurements and echocardiographic recordings. Comparisons were made with
echocardiographic and calibrated carotid pulse data acquired in nine
age-matched normal subjects. The patients with DCM were divided according
to the left ventricular end-diastolic wall thickness-to-dimension ratio
into groups with "appropriate" hypertrophy (i.e., less than or equal to 2
SDs from mean normal; n = 5; group 1) and "inadequate" hypertrophy (i.e.,
greater than 2 SDs from mean normal; n = 8; group 2). Age, New York Heart
Association functional class, left ventricular wall mass index, and left
ventricular end-diastolic pressure and dimension were similar for the DCM
groups. Baseline left ventricular afterload (defined as circumferential
end-systolic wall stress, sigma es) was 168% and 203% greater than normal
in groups 1 and 2, respectively. The administration of the
beta-adrenoceptor agonist dobutamine decreased left ventricular afterload
by 12% in the normal subjects and by 10% in group 1 patients, while
augmenting afterload by 5% in group 2 patients. The latter response
occurred despite a 17% fall in systemic vascular resistance. Overall left
ventricular performance, as assessed by the rate-corrected mean velocity of
fiber shortening (Vcfc), was related to left ventricular afterload (i.e.,
sigma es). The resultant sigma es -Vcfc relationship, a sensitive measure
of left ventricular contractility, was determined over a wide range of
afterload conditions generated by methoxamine (normal subjects) or
nitroprusside (DCM). Baseline left ventricular contractile state was 61% of
normal for group 1 and 44% of normal for group 2. The contractile response
to dobutamine infusion was 52% of normal for group 1 and only 22% of normal
for group 2. Thus, positive inotropic therapy with dobutamine in patients
with DCM is limited by (1) an attenuated contractile response and (2)
elevated left ventricular afterload, which may be augmented further during
its administration.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Physiologic mechanisms governing hemodynamic responses to positive inotropic therapy in patients with dilated cardiomyopathy
Section of Cardiology, University of Chicago, IL.
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