Overview of Current Noninodilator Therapies for Acute Heart Failure Syndromes
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
References (31)
- et al.
Characteristics and outcomes of patients hospitalized for heart failure in the United Statesrationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE)
Am Heart J
(2005) - et al.
Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema
Lancet
(1998) - et al.
Impact of intravenous diuretics on the outcomes of patients hospitalized with Acute Decompensated Heart Failureinsights from the ADHERE Registry
J Card Fail
(2004) - et al.
Diuretic efficacy of high dose furosemide in severe heart failurebolus injection versus continuous infusion
J Am Coll Cardiol
(1996) - et al.
Risk stratification after hospitalization for decompensated heart failure
J Card Fail
(2004) - et al.
Improved left ventricular function during nitroprusside infusion in acute myocardial infarction
Lancet
(1972) - et al.
Randomized controlled trial of vasodilator therapy after myocardial infarction
Am J Cardiol
(1981) - et al.
Comparative hemodynamic and neurohormonal effects of intravenous captopril and digoxin and their combinations in patients with severe heart failure
J Am Coll Cardiol
(1989) - et al.
Does digoxin provide additional hemodynamic and autonomic benefit at higher doses in patients with mild to moderate heart failure and normal sinus rhythm?
J Am Coll Cardiol
(1997) - et al.
Clinical benefits of low serum digoxin concentrations in heart failure
J Am Coll Cardiol
(2002)
Heart Disease and Stroke Statistics—2005 Update
Increased toxicity of high-dose furosemide versus low-dose dopamine in the treatment of refractory congestive heart failure
Clin Pharmacol Ther
Impact of renal insufficiency and chronic diuretic therapy on outcome and resource utilization in patients with acute decompensated heart failure
J Am Coll Cardiol
Continuous infusion of frusemide in refractory oedema [abstract]
BMJ
Continuous infusion of furosemide in the treatment of patients with congestive heart failure and diuretic resistance
J Intern Med
Cited by (23)
ACCF/AHA/ACP/HFSA/ISHLT 2010 clinical competence statement on management of patients with advanced heart failure and cardiac transplant: A report of the ACCF/AHA/ACP task force on clinical competence and training
2010, Journal of the American College of CardiologyCitation Excerpt :Loop diuretics such as furosemide, torsemide, and bumetanide are the mainstay of treatment for volume overload, and knowledge of the pharmacology of each these agents enables the specialist to select the most appropriate agent, dose, and route of administration. The HF specialist should also recognize the deleterious effects of excessive use of diuretics mediated by neurohumoral activation (82), and select the lowest effective dose. Conversely, resistance to diuretic therapy also occurs, and HF specialists must be able to reassess the initial diuretic treatment plan, and adjust the dose of diuretic medication, make use of synergistic diuretic agents, and initiate therapies that augment cardiac output and renal blood flow as indicated on the basis of the patient's response and changing status.
Acute Heart Failure Syndromes
2009, Journal of the American College of CardiologyCitation Excerpt :Initiation or up-titration of evidence-based chronic HF therapies during hospitalization or soon after, absent contraindications, will likely improve post-discharge event rates (128). Pharmacologic therapies have been reviewed extensively elsewhere (126,127,132,133). Dyspnea, along with other symptoms and signs of AHFS, require urgent attention upon presentation.
Emergency Department Stabilization of Heart Failure
2009, Heart Failure ClinicsCitation Excerpt :Although these agents are commonly used, clinical trial data supporting their use in the ED setting are lacking. Clinical trials largely done in the inpatient setting, however, have shown that these therapies improve hemodynamic function, decrease dyspnea, and diminish signs and symptoms of venous congestion.32–36 It is important to note that no pharmacologic agent has been shown to reduce mortality when implemented in the ED for treatment of patients who have acute HF.
Management of Acute Decompensated Heart Failure
2007, Current Problems in CardiologyCitation Excerpt :Neurohormonal activation (renin-angiotensin, endothelin, and BNP) acutely decreases after short-term diuretic therapy designed to lower markedly elevated filling pressures.51 However, over-diuresis can lead to enhanced neurohormonal activation and increased sensitivity to angiotensin-converting enzyme inhibitors and beta-blockers.52 Thus, the lowest dose of diuretic that achieves the desired diuretic effect should be prescribed.
Introduction
2007, American Journal of CardiologyReview of Current and Investigational Pharmacologic Agents for Acute Heart Failure Syndromes
2007, American Journal of CardiologyCitation Excerpt :Despite their clinical use for decades, large-scale randomized controlled trials to define the best strategy for their use (dose and duration) and their effects on clinical outcomes have not been conducted. Clear dosing guidelines are lacking, and dosing choices and administration methods tend to be empiric.11 Continuous infusion of furosemide preceded by a loading dose has been shown to be superior to a single or intermittent intravenous bolus injection of an equal dosage in small studies.12,13