THERAPY AND PREVENTION CARDIOMYOPATHY The differential effects of positive inotropic and vasodilator therapy on diastolic properties in patients with congestive cardiomyopathy

Symptoms of congestive heart failure frequently reflect abnormalities in both systolic and diastolic performance. While much work has been reported regarding the mechanisms by which positive inotropic and vasodilator therapy affect systolic performance, little is known about their effect on diastolic function. In 12 patients with diffuse congestive cardiomyopathy micromanometer left ventricular and aortic pressure measurements were recorded simultaneously with two-dimensionally targeted M mode echocardiograms and thermodilution-determined cardiac output. Each patient received dopamine (2, 4, and 6 gg/kg/min), and dobutamine (2, 6, and 10 ,ug/kg/min), and 10 received nitroprusside (0.125 to 2.0 gg/kg/min). Baseline hemodynamics were characterized by low cardiac index (2.1 ± 0.7 liter/min/m2, mean ± SD), high left ventricular end-diastolic pressure (24 ± 10 mm Hg), and increased end-diastolic (6.8 + 1.0 cm) and end-systolic dimensions (6.0 1.0 cm). All patients had abnormal left ventricular pressure decay with a prolonged time constant (67 ± 20 msec) and reduced peak diastolic lengthening rates. Dopamine and dobutamine decreased the time constant of relaxation and increased the peak lengthening rate. Dobutamine also reduced the minimum diastolic pressure from 14 ± 7 to 10 + 9 mm Hg (p < .01); neither drug reduced end-diastolic pressure. In fact, dopamine elevated end-diastolic pressures in seven patients, despite more rapid pressure decay. Diastolic pressure-dimension relations after dopamine and dobutamine showed a leftward shift with a reduced end-systolic chamber size, but no significant changes in passive chamber stiffness. Nitroprusside decreased left ventricular minimum diastolic pressure by 4 ± 2 mm Hg and end-diastolic pressure by 7 ± 4 mm Hg (p < .0 1). It did not consistently accelerate left ventricular pressure decay at the doses tested. The decreased end-diastolic pressure with nitroprusside was due to a reduced end-diastolic dimension in five patients. In the other patients, all of whom had elevated right atrial pressures, diastolic pressure-dimension relations showed a parallel downward shift after nitroprusside. Thus, positive inotropic therapy with /31-adrenoceptor agonists enhances early diastolic distensibility by accelerating relaxation, augmenting filling, and reducing end-systolic chamber size. Vasodilator therapy is much more effective in lowering diastolic pressures. In some patients this is due to a reduction in extrinsic restraint of the pericardium and/or right ventricular interaction, while in others it simply reflects a decrease in chamber size without alterations in ventricular passive chamber properties. Circulation 74, No. 4, 815-825, 1986. AS OUR UNDERSTANDING of the pathophysiology of the heart failure syndrome has improved, certain classes of drugs have assumed prominent roles in its treatment. The administration of vasodilating agents is From the Department of Medicine, Section of Cardiology and Committee on Clinical Pharmacology, The University of Chicago. Address for correspondence: John D. Carroll, M.D., Cardiology Section, Box 124, The University of Chicago, 5841 South Maryland Ave., Chicago, IL 60637. This work was completed during Dr. Carroll's tenure as a Mellon Foundation Fellow and an Amoco Foundation Scholar. Dr. Lang was supported by a NIH training grant (HL-0738 1). Dr. Rajfer is the recipient of a NIH Clinical Investigator Award (HL-00872). Presented in part at the American Heart Association Scientific Sessions in Washington, D.C., November, 1985. Received March 4, 1986; revision accepted July 17, 1986. Vol. 74, No. 4, October 1986 a logical result of the discovery of abnormal peripheral vascular loading conditions, which elevate resistance to ventricular ejection and produce high filling pressures. 1 Positive inotropic therapy remains a reasonable approach since a reduction in the contractile state of the myocardium appears central to the disease process.2 Little attention has been focused on striking diastolic abnormalities found in the failing heart. In this study we used isovolumetric pressure decay, left ventricular lengthening rates, diastolic pressure-chamber size relations, and pressure measurements throughout diastole to characterize the diastolic properties found in diffusely dilated, cardiomyopathic ventricles. 815 by gest on A ril 5, 2017 http://ciajournals.org/ D ow nladed from