Acutely decompensated heart failure (ADHF)

This chapter will review the pharmacologic management of heart failure (HF) according to the American College of Cardiology Foundation/American Heart Association/Heart Failure Society of America Practice Guidelines.

Definitions

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ADHF: new or worsening signs and symptoms of HF, characterized by acute dyspnea associated with elevated intracardiac filling pressures with or without pulmonary edema.
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HF with reduced ejection fraction (HF r EF): ejection fraction (EF) ≤40%.
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HF with preserved EF (HF p EF): EF ≥50%.
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HF p EF, borderline: EF 41–49%.
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Stages of HF
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  Stage A: normal cardiac function/morphology with increased risk of HF
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  Stage B: abnormal cardiac function/morphology without symptoms of HF
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  Stage C: symptomatic HF
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  Stage D: end-stage HF
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New York Heart Association (NYHA) functional classification:
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  NYHA I: no limitation of physical activity
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  NYHA II: slight limitation of physical activity
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  NYHA III: marked limitation of physical activity
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  NYHA IV: symptoms at rest

Precipitating factors

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Nonadherence with diet
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Worsening renal failure
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Uncontrolled hypertension
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Infection
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Pulmonary embolism
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Myocardial ischemia, arrhythmias
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Hyperthyroidism/hypothyroidism

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Drugs ( Table 2.1 )

Table 2.1

Critical Care Drugs That Can Promote Heart Failure

Data from Page RL II, O’Bryant CL, Chen D, et al. Drugs that may cause or exacerbate heart failure: a scientific statement from the American Heart Association. Circulation . 2016;134:e32–e69.

THERAPEUTIC CLASS AND DRUG	POSSIBLE MECHANISM
Analgesics
NSAIDs (i.e., Ketorolac) COX-2 inhibitors (i.e., Celocoxib)	Prostaglandin inhibition resulting in sodium/water retention and blunted diuretic response
Anesthesia Medications
Desflurane, isoflurane, sevoflurane Dexmedetomidine Etomidate Ketamine Propofol	Myocardial depression and peripheral vasodilation α-Receptor agonist Adrenal suppression Negative inotrope Negative inotrope and vasodilation
Calcium Channel Blockers
Diltiazem, verapamil, nifedipine	Negative inotrope
Anti-Infective Medications
Itraconazole Amphotericin Ampicillin/sulbactam Azithromycin (injection) Metronidazole (injection) Nafcillin Oxacillin Piperacillin/tazobactam Ticarcillin/clavulanate potassium	Negative inotrope Unknown High sodium content “ “ “ “ “ “
Pulmonary Medications
Albuterol	Decreased β-receptor responsiveness with chronic use
Epoprostenol Bosentan	Unknown “
Miscellaneous
Polyethylene glycol Sodium phosphates enema Sodium polystyrene sulfonate	High sodium content in formulation “

COX-2 , Cyclooxygenase-2; NSAIDs , Nonsteroidal antiinflammatory drugs

Pharmacologic management

Vasodilator

For treatment of normotensive or hypertensive HF; lacks unwanted cardiac stimulation ( Table 2.2 )

Table 2.2

Continuous-Infusion Vasodilator Therapy

Data from Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation . 2013;128:1810–1852.

DRUG	STANDARD DOSING (IV)	COMMENT
Nitroglycerin (NTG)	Start at 5 mcg/min Titrate by 5 mcg/min q5min to achieve desired hemodynamic effect Max 200 mcg/min	Preferred vasodilator, especially in patients with CAD Greater venous than arterial vasodilation Tachyphylaxis can occur after 16–24 h of continuous NTG administration ADR: methemoglobinemia (rare) CI: Phosphodiesterase-5 enzyme inhibitors such as sildenafil
Nitroprusside	Start at 5 mcg/min Titrate by 5 mcg/min q5min to achieve desired hemodynamic effect Max dose: 400 mcg/min Max duration: 72 h	Preferred in severe hypertension, acute mitral regurgitation, or acute aortic regurgitation Balanced arterial and venous dilation Monitor for cyanide toxicity Not recommended in renal/hepatic insufficiency CI: myocardial ischemia
Nesiritide (no longer available in U.S.)	Start with a bolus 2 mcg/kg, then 0.01 mcg/kg/min Titrate by 0.005 mcg/kg/min q3h Max 0.03 mcg/kg/min	Recombinant human B-type natriuretic peptide with same natriuretic and vasodilator effects as endogenous BNP Balanced arterial and venous dilation

ADR , Adverse drug reaction; BNP , Brain natriuretic peptide; CAD , Coronary artery disease; CI , Contraindication; IV , Intravenously

Inodilator

For systolic dysfunction when vasodilator therapy is not tolerated due to hypotension ( Table 2.3 )

Table 2.3

Continuous-Infusion Inodilator Therapy

DRUG	STANDARD DOSING (IV)	COMMENT
Dobutamine	Start at 2.5 mcg/kg/min Titrate by 2.5 mcg/kg/min if needed Range: 5–20 mcg/kg/min	Potent β ₁-receptor agonist: positive inotropic effects Weak β ₂≥ α1 receptor agonist: vasodilation in addition to inotropic and chronotropic effects ADR: tachycardia, increase in myocardial O ₂consumption, increase/decrease in blood pressure Least preferred due to deleterious effects of adrenergic stimulation
Dopamine	5–10 mcg/kg/min	Consider in addition to loop diuretic therapy to improve diuresis Dose-related receptor activity: 2–5 mcg/kg/min: dopamine receptor 5–10 mcg/kg/min: β ₁-receptor >10 mcg/kg/min: α ₁-receptor
Levosimendan (not available in U.S.)	Bolus 12 mcg/kg over 10 min, then 0.1 mcg/kg/min Max dose: 0.2 mcg/kg/min Max duration: 24 h	Increases cardiac contractility by sensitizing cardiac myofilaments to calcium Promotes vasodilation by facilitating potassium influx into vascular smooth muscle Preferred agent especially in myocardial ischemia or infarction
Milrinone	Bolus 50 mcg/kg over 10 min, then 0.375–0.75 mcg/kg/min CrCl 50: 0.43 mcg/kg/min CrCl 40: 0.38 mcg/kg/min CrCl 30: 0.33 mcg/kg/min CrCl 20: 0.28 mcg/kg/min CrCl 10: 0.23 mcg/kg/min CrCl 5: 0.2 mcg/kg/min	Phosphodiesterase inhibitor: enhances myocardial contractility and relaxation Less tachycardia than dobutamine but similar risk of ventricular arrhythmias Preferred over dobutamine if recent administration of β-blocker or concomitant pulmonary hypertension Slower onset and longer half-life than dobutamine