Heart Failure: Management¶

Chapter 265 | Part 6: Disorders of the Cardiovascular System · Part 6 – Cardiovascular Disorders · Chapter 265

Key Clinical Points¶

SGLT-2 inhibitors (dapagliflozin, empagliflozin, sotagliflozin) are foundational therapy for symptomatic HF regardless of EF, reducing cardiovascular mortality and HF hospitalizations in HFrEF, HFmrEF, and HFpEF.
In HFpEF, ARNI (sacubitril-valsartan) shows benefit primarily in patients with LVEF <0.60; other agents like ACEIs and ARBs have not conclusively shown mortality reduction in this group.
ADHF management is phenotype-driven: Hypertensive (vasodilators/diuretics), Normotensive/Pulmonary Edema (vasodilators/diuretics/O2), Low Output (inotropes/monitoring), and Shock (inotropes/mechanical support).
Diuretic resistance may be managed by adding acetazolamide, which is particularly useful in the presence of alkalosis (bicarbonate >27 mEq/L).
Nitroglycerin primarily addresses preload; Nitroprusside acts as a potent arterial and venous vasodilator but carries risk of thiocyanate toxicity in renal failure (>72 h).
Nesiritide, Serelaxin, and Ularitide are not recommended as standard therapies for ADHF due to lack of clinical benefit or increased risks (hypotension/worsening creatinine).
High-risk features in ADHF include renal insufficiency, pulmonary edema, hepatic congestion, and cardiogenic shock.
Decongest until euvolemia is achieved; predischarge natriuretic peptide levels are useful for assessing treatment adequacy.
Inotropes (Dobutamine, Milrinone, Levosimendan) are reserved for low-output states or shock.
HFpEF management requires addressing specific comorbidities: obesity, sleep apnea, and anemia/iron deficiency.
Echocardiography is essential to differentiate between true HFpEF and other conditions like infiltrative disease (amyloidosis), hypertrophic cardiomyopathy, or valvular heart disease.

1. DEFINITION & OVERVIEW¶

Heart failure (HF) management is tailored to the clinical phenotype and left ventricular ejection fraction (LVEF).

1.1 Classification by Ejection Fraction • HFrEF: LVEF ≤40% • HFmrEF: LVEF 41–49% • HFpEF: LVEF ≥50%

1.2 Clinical Staging (ACC/AHA) • Stage B: Asymptomatic ventricular dysfunction; amenable to neurohormonal antagonists. • Stage C: Symptomatic HF; management differentiated by LVEF. • Stage D: Advanced or refractory HF; high risk of mortality; consider salvage therapies (transplant, mechanical support) or palliative measures.

1.3 Acute Decompensated Heart Failure (ADHF) • Defined as a heterogeneous clinical syndrome involving decreased cardiac performance, renal dysfunction, and altered vascular compliance. • Morbidity/Mortality: 5% in-hospital mortality; 20% cardiovascular mortality at 1 year. • Readmission: Nearly half of patients are readmitted within 6 months.

2. EPIDEMIOLOGY¶

• Long-term outcomes for HF remain poor. • High-risk features in ADHF (e.g., renal failure, cardiogenic shock) are associated with significantly worse outcomes.

3. ETIOLOGY & PATHOPHYSIOLOGY¶

3.1 HFpEF Pathophysiology • Mechanism: Microvascular endothelial inflammation driven by comorbidities → impaired nitric oxide (NO) signaling → increased myocardial stiffening. • Risk Markers: Hypertension, Hypertrophy, Aging, Fibrosis/altered collagen, Atherosclerosis, Infarction/ischemia, Diabetes, Obesity.

3.2 ADHF Pathophysiology • Result of interrelated abnormalities of cardiac performance, renal dysfunction, and altered vascular compliance.

4. CLINICAL FEATURES¶

4.1 HFpEF Clinical Features • Heterogeneous Group: Includes infiltrative disease (amyloidosis, hemochromatosis, sarcoidosis), storage disease (Fabry, Gaucher), hypertrophic cardiomyopathy, pericardial disease, pulmonary arterial hypertension, valvular heart disease, and primary right ventricular failure. • Comorbidities: Obesity, obstructive lung disease, sleep apnea, chronic kidney disease (CKD), and anemia/iron deficiency. • Functional Impact: Exercise intolerance may be a manifestation of chronotropic insufficiency.

4.2 ADHF Clinical Features • High risk of mortality and frequent readmission (50% at 12 months for CV death, HF hospitalization, MI, stroke, or sudden death).

5. DIFFERENTIAL DIAGNOSIS¶

Patients with normal/near-normal LVEF require careful differentiation from: • Infiltrative heart disease (amyloidosis, hemochromatosis, sarcoidosis) • Storage diseases (Fabry's, Gaucher's) • Hypertrophic cardiomyopathy • Pericardial disease • Pulmonary arterial hypertension • Valvular heart disease • Primary right ventricular failure

6. INVESTIGATIONS & DIAGNOSIS¶

Echocardiography: Essential to identify valvular heart disease and assess LVEF.
Biomarkers of Injury: Natriuretic peptides and cardiac troponins used to stratify risk and assess treatment adequacy.
Predischarge Assessment: Measurement of natriuretic peptide levels before discharge.
Clinical Monitoring: • Weight change as a surrogate for diuresis. • Physical exam: JVP, pulmonary rales, cardiac gallops, peripheral edema, hepatomegaly, and abdominal ascites.

7. MANAGEMENT & TREATMENT¶

7.1 HFpEF Management • Pharmacotherapy: SGLT-2 inhibitors (dapagliflozin, empagliflozin, sotagliflozin) are foundational for all EF types. • ARNI: Benefit primarily in patients with LVEF <0.60. • Supportive Care: Manage obesity, sleep apnea, and anemia; address heart rhythm (atrial fibrillation) and blood pressure.

7.2 ADHF Management: Phenotype-Driven Approach Based on clinical presentation, management is tailored to specific phenotypes: 1. Hypertensive (not volume overloaded) • High-Risk Features: Renal insufficiency, biomarkers of injury. • Treatment: Vasodilators, Diuretics. 2. Normotensive (Pulmonary Edema/Volume Overloaded) • High-Risk Features: ACS, arrhythmia, hypoxia, pulmonary embolism, infection, severe pulmonary congestion, valvular heart disease, opiates, myocardial ischemia, CNS injury, drug toxicity. • Treatment: Vasodilators, Diuretics, O2 and noninvasive ventilation. 3. Low Output (Hypoperfusion/End-Organ Dysfunction) • High-Risk Features: Cool extremities, hepatic congestion. • Treatment: Inotropes, Vasodilators, Hemodynamic monitoring. 4. Shock (Hypotension & Low Cardiac Output) • High-Risk Features: Cardiogenic shock, renal failure. • Treatment: Inotropes (catecholamines), Mechanical circulatory support (IABP, percutaneous VAD, ultrafiltration).

7.3 ADHF Management: Diuretics 1. First Line: Intravenous loop diuretics (Furosemide, Torsemide, Bumetanide) for volume overload. 2. Refractory Cases: Add thiazides (metolazone, chlorthalidone) → Note: Increases risk of hypokalemia. 3. Special Situations: Add Acetazolamide to facilitate decongestion, especially in alkalosis (bicarbonate >27 mEq/L).

7.4 ADHF Management: Vasodilators 1. Nitroglycerin: 10–20 μg/min (up to 200 μg/min). Target: Preload reduction. 2. Nitroprusside: 0.3 μg/kg per min titrated to 5 μg/kg per min. Caution: Thiocyanate toxicity in renal failure (>72 h). 3. Nesiritide: Bolus 2 μg/kg; infusion 0.01 μg/kg per min. (Not recommended as standard due to hypotension risk). 4. Serelaxin: 30 μg/kg per day. (Not approved for clinical practice). 5. Ularitide: 15 ng/kg per min. (No improvement in outcomes; higher rates of hypotension/worsening creatinine).

7.5 ADHF Management: Inotropes 1. Dobutamine: 2–20 μg/kg per min. (Short acting, increased oxygen demand). 2. Milrinone: 0.375–0.75 μg/kg per min. (Avoid initial bolus; reduce dose in renal insufficiency). 3. Levosimendan: 0.1 μg/kg per min (Range: 0.05–0.2). (Long acting; effective regardless of β-blocker use).

7.6 Management Summary Table Reference • ACE Inhibitors: Lisinopril (Target 20–35 mg), Enalapril (10–20 mg bid), Captopril (50 mg tid). • ARBs: Losartan (129 mg), Valsartan (254 mg), Candesartan (24 mg). • MRA: Eplerenone (Target 50 mg), Spironolactone (Target 25–50 mg). • β-Blockers: Metoprolol succinate (159 mg), Carvedilol (37 mg), Bisoprolol (8.6 mg). • SGLT-2i: Dapagliflozin (10 mg), Empagliflozin (10 mg), Sotagliflozin (200 mg).

Key Clinical Pearls¶

• SGLT-2 Inhibitors: Foundational for all EF types; reduce mortality and hospitalization. • ARNI in HFpEF: Benefit primarily when LVEF <0.60. • Diuretic Strategy: Use loop diuretics first; add thiazides for resistance; use Acetazolamide for alkalosis. • Inotropes: Reserved for low output or shock (Dobutamine, Milrinone, Levosimendan). • Vasodilator Selection: Nitroglycerin (preload) vs. Nitroprusside (arterial/venous). Caution with thiocyanate toxicity in renal failure.

Reference Tables¶

TABLE 265-1 Vasoactive Therapy in Acute Decompensated Heart Failure¶

Harrison's 22e, p.1993

DRUG CLASS	GENERIC DRUG	USUAL DOSING	SPECIAL CAUTION	COMMENTS
Inotropic therapy				Use in hypotension, end-organ hypoperfusion, or shock states
	Dobutamine	2–20 μg/kg per min	Increased myocardial oxygen demand, arrhythmia	Short acting, an advantage; variable efficacy in presence of beta blockers (requires higher doses); clinical tolerance to prolonged infusions; concerns with hypersensitivity carditis (rare)
	Milrinone	0.375–0.75 μg/kg per min	Hypotension, arrhythmia	Decrease dose in renal insufficiency; avoid initial bolus; effectiveness retained in presence of beta blockers
	Levosimendan	0.1 μg/kg per min; range, 0.05–0.2 μg/kg per min	Hypotension, arrhythmia	Long acting; should not be used in presence of low blood pressure; similar effectiveness as dobutamine but effectiveness retained in presence of beta blockers
	Nitroglycerin	10–20 μg/min, increase up to 200 μg/min	Headache, flushing, tolerance
	Nesiritide	Bolus 2 μg/kg and infusion at 0.01 μg/kg per min	Hypotension
	Nitroprusside	0.3 μg/kg per min titrated to 5 μg/kg per min	Thiocyanate toxicity in renal insufficiency (>72 h)
	Serelaxin	N/A (tested at 30 μg/kg per d)	Baseline blood pressure should be >125 mmHg
	Ularitide	15 ng/kg per min (48 h)	Baseline blood pressure >116 mmHg
Diuretics				First line of therapy in volume overload with congestion; may use bolus or continuous dosing; initial low dose (1 × home dose) or high dose (2.5 × home dose) equally effective with higher risk of renal worsening with higher dose
	Furosemide	20–240 mg daily	Monitor for electrolyte loss	In severe congestion, use intravenously and consider continuous infusion (not trial supported)
	Torsemide	10–100 mg daily	Monitor for electrolyte loss	High bioavailability, can be given orally; anecdotally more effective in advanced heart failure states if furosemide less bioavailable (due to gut congestion)
	Bumetanide	0.5–5 mg daily	Monitor for electrolyte loss	Can be used orally; intermediate bioavailability
	Adjuvant diuretics for augmentation	N/A	Metolazone, chlorthalidone, spironolactone, acetazolamide	Acetazolamide is useful in presence of alkalosis (bicarbonate level >27mEq/L); metolazone given in 2.5- to 10-mg doses; concomitant use of loop diuretics and thiazides associated with risk for severe hypokalemia, careful laboratory monitoring advised; spironolactone is useful in presence of severe hypokalemia and normal renal function
Placebo

TABLE 265-2 Guideline-Directed Pharmacologic Therapy and Target Doses in Heart Failure with Reduced Ejection Fraction¶

Harrison's 22e, p.1995

DRUG CLASS	GENERIC DRUG	MEAN DAILY DOSE IN CLINICAL TRIALS (mg)	INITIATION (mg)	TARGET DOSE (mg)
Angiotensin-Converting Enzyme Inhibitors
	Lisinopril	4.5–33	2.5–5 qd	20–35 qd
	Enalapril	17	2.5 bid	10–20 bid
	Captopril	123	6.25 tid	50 tid
	Trandolapril	N/A	0.5–1 qd	4 qd
Angiotensin Receptor Blockers
Losartan Valsartan Candesartan	129 254 24	50 qd 40 bid 4–8 qd
Aldosterone Antagonists
	Eplerenone	42.6	25 qd	50 qd
	Spironolactone	26	12.5–25 qd	25–50 qd
Beta Blockers
Metoprolol succinate CR/XL Carvedilol Bisoprolol	159 37 8.6	12.5–25 qd 3.125 bid 1.25 qd
Arteriovenous Vasodilators
	Hydralazine isosorbide dinitrate	270/136	37.5/20 tid	75/40 tid
	Fixed-dose hydralazine/isosorbide dinitrate	143/76	37.5/20 qid	75/40 qid
Angiotensin Receptor-Neprilysin Inhibitor
Sacubitril-valsartan	375	100 bid
SGLT-2 Inhibitor
	Dapagliflozin Empagliflozin Sotagliflozin	10 10 200	10 qd 10 qd 200 qd	10 qd 10 qd 200 qd
Novel Therapies
Vericiguat (sGC stimulator) Omecamtiv mecarbil (myosin activator)	9.2 Not reported	2.5 qd 25 bid

TABLE 265-3 Principles of ICD Implantation for Primary Prevention of Sudden Death PRINCIPLE Arrhythmia–sudden death…¶

Harrison's 22e, p.1999

PRINCIPLE	COMMENT
Arrhythmia–sudden death mismatch	Sudden death in heart failure patients is generally due to progressive LVD, not a focal arrhythmia substrate (except in patients with post-MI HF with scar)
Timing of benefits	LVEF should be evaluated on optimal medical therapy or after revascularization before ICD therapy is employed; no benefit to ICD implant within 40 days of an MI (unless for secondary prevention)