Physiologic Mechanisms Governing Hemodynamic Responses to Positive Inotropic Therapy in Patients with Dilated Cardiomyopathy Positive Inotropic Agents Are an Integral Part of the Treatment of Heart Failure in Patients with Dilated Cardiomyopathy (dcm).1, 2 However, Clinical

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., < 2 SDs from mean normal; n = 5; group 1) and "inadequate" hypertrophy (i.e., > 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, COes) was 168% and 203% greater than normal in groups 1 and 2, respectively. The administration of the 13-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 resistarnce. Overall left ventricular performance, as assessed by the rate-corrected mean velocity of fiber shortening (Vcfc), was related to left ventricular afterload (i.e., Ces). The resultant Qes 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. The ability to separate and quantify abnormalities in left ventricular geometry, loading conditions, and contractile state allows a more thorough interpretation of the hemodynamic responses to a positive inotropic agent and may be useful in determining which patients with heart failure would benefit from treatment with specific cardiotonic agents. Circulation 77, No. 3, 625-637, 1988. POSITIVE INOTROPIC AGENTS are an integral part of the treatment of heart failure in patients with dilated cardiomyopathy (DCM).1, 2 However, clinical From the Section of Cardiology and Committee on Clinical Pharmacology, Departments of Medicine and Pharmacological and Physiological Sciences, The University of Chicago. Supported by National Institutes of Health grants AA-06677 and HL-35480 as well as a Research Service Award training grant HLO72377. Additional support was provided by a grant-in-aid from the Ainerican Heart Association, Chicago Affiliate. Address for correspondence: Kenneth M. Borow, M.D., Director, Cardiac Noninvasive Physiology Lab, University of Chicago Medical Center, 5841 S. Maryland Avenue, Box 44, Chicago, IL 60637. Received May 8, 1987; revision accepted Dec. 3, 1987. Vol. 77, No. 3, March 1988 trials have demonstrated a wide disparity in the hemodynamic responses to these agents even when administered in the same doses to patients with similar symptoms.3 This is due to numerous factors, including (1) interpatient differences in left ventricular contractile state, preload, afterload, heart rate, chamber geometry, and ventricular hypertrophy,6' 7 (2) the variable activation of cardiac and peripheral vascular receptors by the same pharmacologic agent, and (3) the load dependency of traditional measures of overall left ventricular performance (e.g., cardiac output and ejection fraction) as well as their inability to distinguish 625 by gest on A ril 3, 2017 http://ciajournals.org/ D ow nladed from