How Do I Manage Acute Heart Failure?

The vast majority of patients with acute heart failure (AHF) are hospitalized with signs and symptoms of volume overload. Therefore the most important treatment strategy is to alleviate organ congestion, including lung congestion, renal congestion, and liver congestion.

Because elevation of left-sided filling pressure leads to lung congestion, and elevation of right-sided filling pressure leads to liver and renal congestion, alleviating organ congestion requires a reduction of cardiac filling pressures. Among pharmacologic agents that may reduce filling pressures, vasodilators are the most powerful and fastest acting drugs.

How to Unload the Heart with Vasodilators

Vasodilators can reduce the pulmonary capillary wedged pressure and systemic vascular resistance (SVR), which decreases both the preload and the afterload and is likely to increase cardiac output (CO). These favorable effects will appear soon after starting these agents. The European Society of Cardiology guideline and practical recommendation for the management of AHF recommend vasodilator use with normal to high blood pressure (BP) in acute settings. Table 50-1 details the currently recommended agents doses and side effects, and Table 50-2 indicates the mechanisms and hemodynamic effects of each drug. Although vasodilators have many favorable effects, they should be avoided in patients with low admission BP because they may lead to an excessive early drop in systolic BP, which is problematic because vasodilator-induced hypotension has been associated with poor outcomes.

Table 50-1

Recommended Doses and Side Effects of Vasodilators

Drug	Dose	Major Limitations
Nitroglycerin	Start with 10-20 μg/min, 200 μg/min	Hypotension, headache, tachyphylaxis
Sodium nitroprusside	Start with 0.3 μg/kg/min and increase up to 5 μg/kg/min	Hypotension, isocyanate toxicity, coronary steal, rebound vasoconstriction
Nesiritide	Bolus 2 μg/kg + infusion 0.01 μg/kg/min ^∗	Hypotension

∗ Nerisitide can be initiated without bolus.

Table 50-2

Mechanism of Actions and Hemodynamic Effects in AHF

Drugs	Mechanisms	Hemodynamic Effects
Drugs	Mechanisms	CI/CO	PCWP	MAP	HR	SVR	PVR	CBF
Nitroglycerin	NO-mediated vasodilation (vein > artery)	↑	↓	↓	→	↓	↓	↑
Nitroprusside	NO-mediated vasodilation (vein = artery)	↑	↓	↓	→	↓	↓	↓
Nesiritide	cGMP-mediated vasodilation in both endothelial and vascular smooth muscle cells	↑	↓	↓	→	↓	↓	↑

AHF, acute heart failure; CBF, cerebral blood flow; CI, cardiac index; cGMP, cyclic 3′’,5’-guanosine monophosphate; CO, cardiac output; HR, heart rate; MAP, mean atrial pressure; NO, nitric oxide; PCWP, pulmonary capillary wedged pressure; PVR, peripheral vascular resistance; SVR, systemic vascular resistance.

Importantly, while vasodilator therapy has been extensively used to treat heart failure, its value has never been demonstrated in a prospective clinical trial. Such studies that have been performed have not provided a significant alteration in mortality or readmission rates.

Nitroglycerin

Nitroglycerin is a powerful venodilator and a mild arterial dilator. Its immediate effects occur primarily through venodilation, which lowers preload and, to a lesser extent, afterload, and increases CO. Because of its favorable effect on hemodynamic profiles in patients with AHF, nitroglycerin is widely used in acute settings throughout the world. When BP is adequate, nitroglycerin can be administered sublingually while preparing for intravenous treatment. Intravenous nitroglycerin is usually started at ≈ 5 to 10 μg/min and is titrated until symptoms improve (i.e., when a favorable hemodynamic response is observed) or until the patient has side effects or reaches the maximum dose (200 μg/min). Tachyphylaxis can develop within 24 hours, which can lead to an escalation in dose to achieve the desired effect.

Sodium Nitroprusside

The use of sodium nitroprusside has decreased in recent years. This agent can unload the heart through balanced venodilation and arteriodilation, lowering left and right heart filling pressures (preload and afterload) and increasing CO. Nitroprusside is particularly useful in the acute setting, which includes hypertensive crisis and acute valvular regurgitation. Invasive hemodynamic monitoring is recommended to avoid hypotension. Nitroprusside should be avoided in patients with active ischemia because it dilates resistance vessels in nonischemic myocardium, which can lead to the coronary steal phenomenon. In general, a nitroprusside infusion is started at 0.3 μg/kg/min and titrated gradually until symptoms improve. Long-term use, high doses, or renal dysfunction have been associated with the risk of isocyanate toxicity. For rebound vasoconstriction to be avoided, nitroprusside must be tapered gradually.

Nesiritide

Nesiritide is a recombinant form of human B-type natriuretic peptide and has variable effects. Through its main activity, vasodilation, nesiritide can reduce SVR, increase CO, and increase sodium urinary excretion. However, in the Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE) trial, nesiritide was not found to be superior to placebo with respect to urine output (see later section on dopamine). Nesiritide infusions can be started at 0.01 μg/kg/min without need for a bolus. If hypotension occurs during infusion, the dose should be reduced or discontinued and, after BP is restored, restarted at a 30% lower dose. Nesiritide does not cause tachyphylaxis.

How to Reduce Extracellular Volume

Loop Diuretics

Loop diuretics are the most widely used agents worldwide and are commonly used to treat heart failure ( Table 50-3 ). Loop diuretics inhibit sodium/potassium/chloride cotransporters at the luminal membrane, so they should be secreted into tubular lumen by the organic acid transporter (OAT). Intravenous administration of loop diuretics can cause mild venodilation with a decrease in cardiac preload before diuretic response, an action that also contributes to rapid improvement of symptoms. Loop diuretics induce the formation of urine that contains 0.45% sodium chloride (natriuresis). The effects of loop diuretics are powerful, and urine substantially comes from the intravascular space, indicating that excessive and sudden urine output could lead to deleterious hemodynamic changes and also adversely affect the renin angiotensin aldosterone system. There are a significant number of patients who exhibit diuretic resistance. The etiology of this phenomenon is multifactorial and complex, but renal dysfunction is the most important cause. The dose of agent secreted into the tubular lumen will be decreased in patients with renal dysfunction and may require titration of the dose. In addition, loop diuretics compete with other organic acids for access to the OAT receptor. The accumulation of these acids in renal impairment could therefore lead to diuretic resistance.

Table 50-3

Characteristics of Decongestive Agents

Modality	Urine Na Excretion	RAA Activation	IV Volume	eGFR	CO	PCWP	RAP	PAP	SVR	PVR	Amount of Urine	Bioavailability
Intravenous diuretic	Hypotonic with plasma (half normal saline)	↑↑↑	↓	→, ↓	↓	↓	↓	↓	↑	↑	Unpredictable	10-100 (%)
Tolvaptan	None ^∗	→, ↑	?	→	→	↓	↓	↓	→	→, ↓	Unpredictable	42-80 (%)
Ultrafiltration	Isotonic with plasma	↓	→	→	→, ↑	↓	↓	↓	→	→, ↓	Controllable, adjustable	(-)