Management of Acute Decompensated Heart Failure in Hospitalized Patients

The large ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) randomized ADHF patients to nesiritide or placebo and tested the hypothesis that nesiritide would be superior to placebo in improving acute dyspnea, all-cause mortality, and heart failure readmission in patients presenting with ADHF [42]. Nesiritide-treated patients showed only a modest early improvement in self-assessed dyspnea and no difference in the composite endpoint of death or rehospitalization at 30 days in patients admitted with ADHF. Reassuringly, there was no increase in renal failure compared to placebo; however, the incidence of symptomatic hypotension was higher with nesiritide [42]. Although nesiritide remains in the armentarium of vasoactive medications for ADHF, less expensive vasodilators such as nitroglycerin or nitroprusside may be preferred by many clinicians.

Overall, vasodilators represent a good treatment option for patients presenting with ADHF characterized by low cardiac output, high filling pressures, and elevated systemic vascular resistance. There is no clear evidence, however, to suggest that IV vasodilators improve survival in hospitalized patients with ADHF; thus, its use should be restricted to the relief of dyspnea in patients with stable blood pressure [5].

Inotropic Therapy

The most commonly used positive inotropic agents in the management of patients with ADHF in the United States are dobutamine (beta-1, beta-2, and alpha adrenoreceptor agonist) and milrinone (phosphodiesterase-III inhibitor) [38]. Inotropes increase cardiac output by increasing myocardial contractility, reduce left and right ventricular filling pressures, and improve hemodynamic parameters. Despite these hemodynamic effects, inotropic agents have not demonstrated a survival benefit in patients with ADHF. A major limitation regarding these agents is that they increase the risk of cardiac arrhythmias by increasing intracellular calcium in cardiac myocytes. In fact, retrospective analyses suggest that most inotropic agents are associated with an increased risk of death [38,43].

Milrinone inhibits type III isoform of the enzyme phosphodiasterase leading to an increase in intracellular cyclic AMP to exert its positive inotropic effect on the myocardium. Milrinone also exerts systemic and pulmonary vasodilator effects in the circulation decreasing right atrial, pulmonary capillary wedge, and mean arterial pressure. In the OPTIME-CHF trial, patients with chronic heart failure admitted to the hospital with ADHF were randomized to short term infusion of milrinone vs. placebo plus standard therapy. Milrinone resulted in more hypotension, atrial fibrillation and ventricular arrhythmias without any benefit on mortality or re-hospitalization [44].A retrospective analysis from the ADHEREregistry showed that in-hospital mortality was twofold higher with the use of dobutamine or milrinone in patients with ADHF when compared to treatment with vasodilators [38].

Dobutamine is a beta-1, beta-2, and alpha adrenoreceptor agonist that works by increasing myocardial contractility leading to an increase in cardiac output as its primary cardiovascular effect. Currently, routine use of IV positive inotropic agents in the absence of imminent cardiogenic shock or low output ADHF with systemic hypoperfusion is generally not recommended due to concerns of adverse effects [5]. The ACCF/AHA guidelines recommend the use of positive inotropic agents to relieve symptoms, improve systemic perfusion and preserve end-organ function in patients with severe left ventricular systolic failure and low output syndrome with evidence of end-organ dysfunction (such as hypotension, altered mentation, cool extremities, low urine output and serum markers indicative of renal and/or hepatic dysfunction) with or without congestion [5].