Pharmacologic Therapy

The choice of pharmacologic agents depends on the patient’s hemodynamic profile:

Warm and Dry: (CI greater than 2.2 L + PCWP less than 18 mm Hg)

• Focus on optimizing chronic oral heart failure therapies
  • Initiate/uptitrate beta-blockers (e.g. carvedilol, metoprolol succinate) and ACE inhibitors or ARBs (e.g. lisinopril, losartan) as tolerated
  • Add hydralazine and nitrates (e.g. isosorbide dinitrate) in African American patients
  • Consider adding angiotensin receptor-neprilysin inhibitor (sacubitril/valsartan) for HFrEF if tolerated
  • Continue other oral therapies (digoxin, loop diuretics) if previously prescribed

Warm and Wet: Without Flash Pulmonary Edema (CI> 2.2 L + PCWP greater than 18 mm Hg)

• Intravenous loop diuretics (furosemide 20-40 mg IV or bumetanide 1-2 mg IV)
• Double patients’ oral daily loop diuretic dose for initial IV dose
• If oral loop diuretic naive, start furosemide 40 mg IV daily or bumetanide 2 mg IV daily
• Monitor urine output, symptoms, weight loss
• Repeat doses every 2 hours as needed
• For diuretic resistance:
  • Increase loop diuretic dose
  • Add metolazone 2.5-10 mg oral daily
  • Switch to continuous infusion loop diuretic
  • Consider ultrafiltration
• Add intravenous nitroglycerin infusion if persistent symptoms, start at 5-10 mcg/min, titrate by 5-10 mcg/min every 5 minutes, max 200 mcg/min
• For hypertensive patients, sodium nitroprusside 0.3-5 mcg/kg/min IV is an alternative to nitroglycerin

Warm and Wet: Flash Pulmonary Edema (CI> 2.2 L + PCWP greater than 18 mm Hg)

A subset of warm and wet profile patients present with flash pulmonary edema, characterized by:

• Abrupt onset dyspnea and hypoxemia
• Pink, frothy sputum
• Hypertensive crisis (SBP > 180 mmHg)
• Bilateral pulmonary rales

Management should focus on rapid symptom relief:

• High dose intravenous nitroglycerin
  • Options:
    • Intravenous bolus of 2000 mcg every 3-5 minutes as needed
    • Intravenous infusion at 100-200 mcg/min
  • Titrate to relief of dyspnea and oxygenation improvement
  • Wean infusion as symptoms and blood pressure improve
• Non-invasive positive pressure ventilation
• Consider intravenous enalaprilat 0.625-1.25 mg if blood pressure remains elevated after nitroglycerin
• Cautious use of intravenous furosemide 20-40 mg to relieve fluid overload after stabilization with above measures

Cold and Dry:(CI less than 2.2 L + PCWP less than 18 mm Hg)

• Assess PCWP
  •  If <15 mm Hg, administer IVF
  • If 15-18 mm Hg, assess for systemic hypotension
    •  Mean arterial pressure (MAP):  2/3 DBP + 1/3 SBP
• Cautious intravenous fluids 250-500 mL to increase preload
• Consider holding loop diuretics temporarily
• Inotropes if fluid bolus insufficient:
  • Dobutamine 2-20 mcg/kg/min IV
  • Milrinone 0.375-0.75 mcg/kg/min IV
    • Small trials directly comparing these agents in ADHF have resulted in no difference in clinical outcomes

• Titrate to target CI > 2.2 L/min/m2 and MAP > 65 mmHg
• Add norepinephrine if MAP remains low after inotrope initiation

Cold and Wet: (CI less than 2.2 L + PCWP greater than 18 mm Hg)

• Intravenous loop diuretics as above to relieve congestion
• Inotropes as above to improve cardiac output
• Vasopressors if inotropes cause hypotension:
  • Norepinephrine 0.2-1 mcg/kg/min IV
  • Dopamine 2-10 mcg/kg/min IV
• Target CI > 2.2 L/min/m2, MAP > 65 mmHg, PCWP 15-18 mmHg
• Consider mechanical circulatory support if refractory

Loop Diuretics

• Furosemide, bumetanide are first-line
• Initiate with IV bolus or infusion at 1-2.5 times oral dose
• Adjust dose based on urine output, weight loss, symptoms
• Monitor electrolytes, renal function
• Overcoming Resistance
  • Increase loop diuretic dose
  • Add thiazide diuretic (e.g. metolazone, chlorothiazide)
  • Switch to continuous infusion
  • Consider ultrafiltration

---

Nonpharmacologic Therapies

• Sodium restriction
• Ultrafiltration for diuretic resistance
• Temporary mechanical circulatory support (MCS) for refractory ADHF
• Durable MCS or cardiac transplantation in advanced heart failure

Evaluation of Therapeutic Outcomes

• Monitor symptoms, vital signs, orthostasis, weights, electrolytes, renal function
• Assess response to intravenous therapies
• Prepare for discharge once euvolemic and stable on oral agents
• Initiate/optimize guideline-directed medical therapies prior to discharge
• Schedule prompt follow-up appointment and testing after discharge