Overview of Current Noninodilator Therapies for Acute Heart Failure Syndromes

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Several treatment strategies exist for patients hospitalized with acute heart failure syndromes (AHFS). These therapies traditionally focus on improving hemodynamics and relieving congestion. This review focuses on noninodilator therapies, including diuretics, nitrovasodilators (nitroprusside and nitroglycerin), vasodilators (nesiritide), digoxin, and intravenous angiotensin-converting enzyme inhibitors. These agents are used based on their associated symptomatic improvements alone. In the hospitalized setting, none of these agents have demonstrated benefits on long-term outcomes. Future work in AHFS should strive to understand the influence of conventional and new pharmacologic therapies on the underlying pathophysiology of AHFS, the processes that lead to myocardial injury and progressive heart failure, and measurable clinical outcomes.

Section snippets

Diuretics

Loop diuretics are the main component of AHFS therapy. Furosemide was approved by the US Food and Drug Administration (FDA) in 1966. These drugs inhibit the reabsorption of sodium and chloride in the ascending limb of the loop of Henle by interfering with the chloride binding of the Na+–K+–2Cl− cotransport system, thereby altering electrolyte transfer in the proximal tubule. The increased urinary excretion of sodium, chloride, potassium, and hydrogen ions results in diuresis. Loop diuretics

Nitrates

The nitrates nitroprusside and nitroglycerin exert their effects through direct vasodilatory actions on arterial and venous smooth muscle. Both agents are primarily venodilators, with nitroglycerin providing more selectivity for venodilation than nitroprusside. This vasodilation reduces preload and afterload and increases cardiac index and stroke volume. Nitroglycerin and nitroprusside are converted to nitric oxide. Nitric oxide activates the enzyme guanylate cyclase and stimulates the

Digoxin

Digoxin has been a component of treatment for chronic HF for hundreds of years. Digoxin inhibits the sodium–potassium adenosine triphosphatase pump, leading to an increase in intracellular sodium.25 This action results in a decrease in calcium efflux via the sodium–calcium exchange system, and ultimately increases cytoplasmic calcium, which contributes to an increase in contractility.

Digoxin reduces PCWP, improves LVEF, and increases cardiac output in patients with systolic dysfunction and

Neurohormonal Antagonists: Intravenous Angiotensin-Converting Enzyme Inhibitors

Intravenous ACE inhibitors are not routinely recommended or indicated in the initial stabilization of patients with AHFS.20 Studies that have evaluated intravenous ACE inhibitors in the acute setting have focused on patients in the setting of acute MI. In the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II), there was no benefit to early intravenous enalapril administration in patients with acute MI.31 Although some small studies have demonstrated hemodynamic improvements

Role of Noninodilator Agents in Therapy

Each agent discussed in this review has a role in the management of AHFS. However, the choice of therapy is largely empiric and is not driven by clinical trial evidence guiding the use of these therapies. The best clinical situation in which to use a specific therapy is often unclear to the practicing physician. The following list highlights some general considerations clinicians may use to determine appropriate therapy:

  • •

    Loop diuretics: use in patients with signs and symptoms of congestion,

Conclusion

Research in AHFS is receiving more attention within the HF community. Increased attention is being focused on understanding the pathophysiology, appropriate therapeutic targets, and optimal clinical trial designs for this population. Although this article describes current noninotropic therapies for acute HF, none of the therapies discussed have been shown to reduce the mortality and morbidity associated with this highly prevalent syndrome. These traditional therapies focus on normalizing

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