More than 6.5 million adults in the United States have heart failure, the prevalence of which is expected to increase by 25% by the year 2030.1 Admission rates for heart failure remain high, and hospitalizations account for the majority of the direct costs associated with its management.2,3 Among patients hospitalized with heart failure, nearly 1 in 4 are readmitted within 30 days.2
Managing these patients in the inpatient setting often involves careful titration of intravenous (IV) and oral therapies with complex hemodynamic effects. It is important for pharmacists to have a basic understanding of these management strategies in order to help facilitate and monitor appropriate therapy and improve outcomes.
Patients presenting with fluid overload may experience dyspnea at rest or on exertion, paroxysmal nocturnal dyspnea, orthopnea, peripheral edema, abdominal swelling, rales, elevated jugular venous pressure, or nausea and vomiting, all often accompanied by weight gain. Signs of low cardiac output and hypoperfusion include worsening renal function, altered mental status, fatigue, and hypotension.4,5
In addition to addressing the reversible and treatable causes of heart failure, management of acutely decompensated patients is focused on improving symptoms, improving hemodynamic parameters, and ultimately optimizing chronic medications known to improve outcomes. On discharge and during follow-up, medication management and titration are paramount to improving these outcomes.
Much as the diagnosis of heart failure is based upon the presenting signs and symptoms, these signs and symptoms help guide therapy. For patients presenting with fluid overload, there are several approaches to help facilitate diuresis.In addition to sodium and fluid restriction, converting to an IV loop diuretic (furosemide or bumetanide), typically done in tandem with increasing the loop diuretic dose, is a common initial strategy. IV diuretic administration can facilitate more rapid onset of diuresis as well as avoid potential absorption concerns with orally administered diuretics (eg, furosemide).
For patients in whom diuresis remains difficult, the addition of a thiazide diuretic (typically metolazone or IV chlorothiazide) may be beneficial.4,5
Close electrolyte monitoring is important, particularly in the setting of aggressive diuresis. In addition, monitoring should include urine output, fluid intake, renal function, vital signs, and daily weights to assess progress.
Continuous infusion of a loop diuretic is noted as an option by both the Heart Failure Society of America and American College of Cardiology/American Heart Association Practice Guidelines for diuretic resistance.4,5
Although concerns have been raised over the potential effects of high bolus doses, a recent trial examining the utility of continuous infusion loop diuretics found no differences between intermittent and continuous infusion with respect to effects on renal function.6
The DOSE trial examined whether high-dose loop diuretic (given intravenously at 2.5 times the patient’s home dose) versus low dose and whether continuous infusion versus intermittent boluses doses led to greater improvements in global symptom assessment or change in serum creatinine at 72 hours in patients admitted with an acute decompensation. Analysis of secondary end points suggested greater net fluid loss and greater improvements in selfreported dyspnea in patients randomized to high-dose diuretics. Continuous infusion of loop diuretics remains an option, but the advantages of continuous infusion compared with bolus dosing remains unclear.
Ultrafiltration is another option for patients with diuretic resistance. The UNLOAD study demonstrated greater net fluid and weight loss at 48 hours and a reduction in hospitalization for heart failure at 90 days in patients with heart failure and signs of fluid overload randomized to ultrafiltration versus standard therapy.7
No differences in chan-ges in renal function were noted between groups. In contrast, the CARRESS-HF study found that a stepped pharmacologic therapy algorithm (goal 3 to 5 liters negative per day) was superior to ultrafiltration with respect to preservation of renal function in patients admitted with heart failure with signs of fluid overload and worsening renal function.8
Weight loss was similar between groups. In the inpatient setting, barriers to ultrafiltration include the need for more frequent monitoring and a higher level of nursing care, anticoagulation (eg, heparin) to prevent filter clotting, and the high cost of filter replacement. In light of the results of the CARRESSHF trial, ultrafiltration in patients with acutely decompensated heart failure and worsening renal function should be avoided. Ultrafiltration remains a potential strategy for patients with diuretic resistance and fluid overload in the absence of renal dysfunction.
Vasodilators are generally used as an adjunct to diuretic therapy in patients with continued signs of congestion despite diuretics, or in patients with acute pulmonary edema or severe hypertension.4,5
They can also be used to lower afterload in patients with low cardiac output with the goal of improving forward flow. Oral vasodilators including angiotensin-converting enzyme (ACE) inhibitors can be used to manage stable patients, although titration is generally slower due to the longer relative half-lives of oral medications.
For more acutely ill patients, IV vasodilators may be warranted. The immediate goals of vasodilator therapy vary based on patient presentation, but include relief of congestion, improved diuresis, and improved cardiac output and end-organ perfusion. Hypotension is common, and patients should have frequent blood pressure monitoring while receiving IV vasodilators.
Nitroglycerin reduces congestion primarily through venodilation, although decreases in afterload can be seen with high doses. The use of nitroglycerin is limited by tachyphylaxis and adverse effects, generally hypotension and headache.4,5,9
In contrast to nitroglycerin, nitroprusside has both arterial and venodilating properties and can be advantageous in patients with elevated filling pressures, low cardiac output, and adequate blood pressure.
Hemodynamic monitoring is important, particularly with nitroprusside, due to the potential for profound decreases in blood pressure. Thiocyanate toxicity is rare but can occur with high doses or renal dysfunction.4,5,10
Data evaluating the use of nitroprusside and nitroglycerin in the acute decompensated heart failure population are limited.
Nesiritide is a B-type natriuretic peptide with preload and afterload lowering and other potential beneficial effects.11
Initial clinical studies showed rapid improvements in pulmonary capillary wedge pressure compared with placebo.11,12
Subsequently, 2 meta-analyses were published suggesting an association between nesiritide and renal failure and increased mortality.13,14
More recently, a randomized controlled trial (ASCEND-HF) found no difference in patient-reported symptoms of dyspnea at 6 or 24 hours, nor did it find differences in mortality or hospitalization for heart failure at 30 days in patients randomized to nesiritide versus placebo.15
The ultimate benefit of nesiritide in acute decompensated heart failure remains unclear. Table 1 summarizes the vasodilators used in acute decompensated heart failure.
Patients for whom IV vasodilator therapy is deemed necessary should be monitored closely for hypotension, changes in renal function, and signs of improvement in diuresis and cardiac output. Due to the inherent limitations of continued IV therapy, transition to oral medications should occur when the patient is clinically stable. ACE inhibitors and hydralazine are used commonly when weaning IV vasodilators, though frequent monitoring remains necessary until the IV agents have been weaned successfully.
Inotropes are typically reserved for patients with low left ventricular ejection fraction presenting with signs and symptoms of low cardiac output and hypoperfusion. Inotropes are also used as palliative therapy in patients with end-stage disease, or as a bridge to advanced therapies including left ventricular assist device or heart transplantation. In patients with symptomatic hypotension who are unable to tolerate vasodilators, inotropes may be indicated. However, the use of inotropes in patients without signs of hypoperfusion is not recommend due to the high incidence of adverse effects without demonstrated benefits.4,5
Dobutamine and milrinone are the most frequently encountered agents in patients with acute decompensated heart failure requiring inotropes. Milrinone has both peripheral and pulmonary vasodilating effects in addition to inotropic effects. Although some vasodilation may occur with dobutamine through beta2
receptor stimulation, milrinone has greater vasodilatory effects and should be used cautiously in patients with low systemic vascular resistance.4,5
Dopamine can be used to supplement inotropic support, although increases in systemic vascular resistance can become problematic with dose escalation in patients with compromised cardiac output.
The choice of inotrope depends on patient-specific parameters and must be weighed closely. In patients with normal or elevated systemic vascular resistance, milrinone may be warranted due to more pronounced effects on systemic vascular resistance than dobutamine. In patients with renal dysfunction, milrinone clearance may be prolonged. Patients must be monitored closely for hemodynamic changes and signs of improvement. Table 2 summarizes the inotropes that are commonly used.
Inotropes are not without adverse effects. In the ADHERE registry, inotropes were associated with higher in-hospital mortality than vasodilators in patients presenting with acute decompensated heart failure.16
In the OPTIME-CHF study, patients randomized to milrinone experienced more sustained hypotension and atrial arrhythmias than the placebo group.17
Patients should be monitored closely for tacharrhythmias. Current practice guidelines recommend vasodilators be considered over inotropes in patients with acute decompensated heart failure and adequate blood pressure.5
Role of the Pharmacist
Management of acute decompensated heart failure in the inpatient setting can be challenging. Pharmacists can play a critical role in managing these patients by providing recommendations on drug titration and monitoring, dose adjustments based on patient-specific parameters, and providing assistance with optimizing oral therapy. Pharmacists in both the inpatient and outpatient settings have the opportunity to ensure appropriate transition of care from one setting to another. Through patient and provider education and assessment of appropriate therapy, the pharmacist can help to ensure optimal outcomes and improve overall care.
John E. MacKay, PharmD, BCPS, graduated from Oregon State University College of Pharmacy and completed both his pharmacy practice and cardiology specialty residencies at the University of North Carolina Hospitals and Clinics in Chapel Hill, North Carolina. He currently works as a clinical pharmacist in advanced heart failure at Oregon Health and Science University.
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