CONGESTIVE HEAR7 FAILURE Hemodynamic and Neurohormonal Effects of Quinidine in Patients with Severe Left Ventricular Dysfunction Secondary to Coronary Artery Disease or Idiopathic Dilated Cardiomyopathy Stephen S. Gottlieb, MD, and Michelle Weinberg, RN Quinidine causes vasodilation directly and by inhibi- tion of adrenergic vasoconstriction, but it also ex- erts negative inotropic activity. Although this drug is often administered to patients with severe con- gestive heart failure, the net consequences of these opposing actions have not been evaluated in such patients. The hemodynamic and neurohormonal re- sponse to oral quinidine (600 mg) in 19 patients with severe chronic heart failure was therefore de- termined. Vasodilation was the predominant effect of quinidine, with reductions in mean arterial, left ventricular filling and right atriai pressures of -9% (confidence interval [Cl] -5 to -13), -8% (Cl -19 to 3), -15% (Cl -26 to -4), respectively. The quinidine-induced vasodilation increased plasma norepinephrine and epinehrine concentrations by 44% (Cl +17 to +72) and 47% (Cl +2 to +91), re- spectively. No change in cardiac performance was noted, with the cardiac index slightly increased (+lO%, CI +2 to +17) and stroke work index un- changed (O%, Cl -11 to +ll) after quinidine. Al- though the mean serum quinidine concentration was within the therapeutic range or lower in all pa- tients, the serum quinidine concentration and the change in mean arterial pressure did correlate (r* = 0.64). In conclusion, vasodilation is the predomi- nant hemodynamic effect of oral quinidine in pa- tients with congestive heart failure. However, po- tential adverse effects may be caused by conse- quent neurohormonal activation. (Am1 Cardiol 1991;67:726-731) From the Division of Cardiology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland. Manuscript received October 8. 1990: revised manuscriut received and accented December 17, 1990: Addressfor reprints: Stephen S. Gottlieb, MD, Division of Cardiol- ogy, The University of Maryland Schoolof Medicine, 22 South Greene Street, Baltimore, Maryland 21201. P atients with congestive heart failure may exhibit adverse hemodynamiceffectswhen given a medi- cation that causesno such problems in normal persons.For example, we have demonstrated that the administration of antiarrhythmic agents thought to possess minimal negative inotropic activity may cause marked clinical and hemodynamic deterioration when given to a patient with severe left ventricular (LV) dys- function. Although encainide, tocainide and mexiletine reportedly have minimal hemodynamic consequences in personswith normal cardiac function, we observed marked increases in LV filling pressure and decreases in cardiac output when theseagentswere given to patients with severe heart failure.’ There are reasons to suspect that the hemodynamic actions of quinidine could have considerableimpact in patients with congestive heart failure, but quinidine’s clinical effectsare difficult to predict because of its vari- ous hemodynamic actions. As with other antiarrhyth- mic agents, quinidine exerts negative inotropic activity when studied in vitro,2 but unlike most other antiar- rhythmic agentsit also is a vasodilator.3 Clinical studies have not noted appreciable hemodynamic effects with quinidine, but this drug has never been studied in pa- tients with severe LV dysfunction using invasive hemo- dynamic monitoring. This is important information, be- cause patients with heart failure are frequently given quinidine for ventricular or supraventricular arrhyth- mias. We therefore evaluated the effectsof quinidine in patients with severe congestive heart failure using inva- sive hemodynamic monitoring. METHODS Patients: We studied 19 patients with severe LV dysfunction who were referred for the treatment of re- fractory heart failure. There were 17 men and 2 women aged 34 to 82 years (mean age f standard error of the mean 59 f 3). All patients had a LV ejection fraction <40% by radionuclide angiography (range 8 to 39%, mean 21 f 2). The causeof heart failure was coronary artery disease in 8 patients and dilated cardiomyopathy in 11 patients. Thirteen patients were in New York Heart Association functional class III and 6 were in class IV. All patients were receiving constant doses of digitalis and diuretic drugs; previous therapy with vaso- dilator or antiarrhythmic drugs was withheld for 124 hours before entry into the study. 728 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 67