To examine the effect of milrinone on myocardial energetics in patients with congestive heart failure, we measured systemic, pulmonary, and coronary hemodynamics in 18 patients before and after intravenous administration of milrinone (125 36 Mg/kg). There was a 45% increase in cardiac index (2.1 ± 0.5 to 3.0 0.6 liters/min/m2; p = .0001), a 39% fall in the pulmonary capillary wedge pressure (28 + 8 to 17 + 8 mm Hg; p = .0001), and a 42% increase in left ventricular external work (3758 ± 1419 to 5340 1598 g-m/min; p = .0001). Both the heart rate-blood pressure product (9624 + 2272 to 9380 2428 mm Hg-beats/min; p = NS) and regional left ventricular myocardial oxygen consumption (7.6 ± 2.9 to 8.1 ± 3.1 ml 02/min; p = NS) were unchanged after milrinone, resulting in a 45% increase in calculated left ventricular external efficiency (p = .004). Although myocardial oxygen consumption did not change, regional great cardiac venous blood flow increased significantly (73 ± 32 to 85 34 ml/min; p .02) as a result of a 30% reduction in regional coronary vascular resistance (1.32 0.99 to 0.93 0.54 mm Hg-min/ml; p = .004), a decrease comparable to the concurrent 37% and 38% falls seen in systemic and pulmonary vascular resistances, respectively. These changes were associated with an 1 1 % fall in the transcoronary arterial-venous oxygen difference (111 + 24 to 99 + 21 ml/02/liter; p = .0001), which is consistent with a primary coronary vasodilator effect of milrinone. Thus, milrinone enhances cardiac performance without a systematic increase in myocardial oxygen consumption, i.e., it increases left ventricular external efficiency. Furthermore, milrinone may improve coronary flow reserve by direct coronary vasodilation and/or reduction in left ventricular diastolic pressure. Circulation 71, No. 5, 972-979, 1985. MILRINONE, a bipyridine compound, causes major hemodynamic improvement in patients with advanced congestive heart failure" 2by a combination of positive inotropic" 3-S and systemic arteriolar vasodilatorl 6 effects. Although a reduction of left ventricular systolic and diastolic pressures might be expected to improve myocardial oxygen balance through reduced myocardial work7-9 and improved subendocardial blood flow,'102 respectively, these potential benefits may be From the Charles A. Dana Research Institute and the Harvard-Thorn-

The safety and efficacy of long-term oral milrinone therapy were evaluated over a 2 1/2 year period in 100 patients who had severe congestive heart failure despite conventional therapy. Long-term oral milrinone therapy (27 +/- 8 mg/day initial dose) was well tolerated; drug-related side effects occurred in only 11% of patients and led to drug withdrawal in only 4% of patients. Of 94 patients evaluated after 1 month of therapy, 51% had improved by at least one New York Heart Association functional class. Despite hemodynamic and clinical improvements, life table analysis showed a 39% mortality rate at 6 months and a 63% mortality rate at 1 year of therapy. Characteristics at study entry that predicted death within 6 months included more advanced functional class, impaired renal function, lower right ventricular ejection fraction, presence of nonsustained ventricular tachycardia on 24 hour ambulatory electrocardiography, more impaired baseline hemodynamic function and absence of clinical improvement after 1 month of milrinone therapy. Multivariate analysis selected lower baseline cardiac index and aortic systolic pressure as the most significant variables in predicting death; patients who died of progressive heart failure had less frequent use of antiarrhythmic drugs and greater increases in furosemide and milrinone doses during long-term follow-up than did those who died suddenly. Thus, although milrinone is well tolerated and produces early symptomatic benefits in approximately half of patients with congestive heart failure refractory to conventional therapy, there is no evidence that it improves the high baseline mortality in this disorder.

Sulfonylurea therapy appears to attenuate the magnitude of ST-segment elevation during an AMI, resulting in failure to meet criteria for thrombolytic therapy and as a consequence leading to inappropriate withholding therapy in this subset of diabetic patients.

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