Congestive heart failure pharmacotherapy

Congestive Heart Failure Microchapters
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Pathophysiology Systolic Dysfunction Diastolic Dysfunction HFpEF HFrEF
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Medical Therapy:
Summary
Acute Pharmacotherapy
Chronic Pharmacotherapy in HFpEF
Chronic Pharmacotherapy in HFrEF Diuretics ACE Inhibitors Angiotensin receptor blockers Aldosterone Antagonists Beta Blockers Ca Channel Blockers Nitrates Hydralazine Positive Inotropics Anticoagulants Angiotensin Receptor-Neprilysin Inhibitor Antiarrhythmic Drugs Nutritional Supplements Hormonal Therapies Drugs to Avoid Drug Interactions Treatment of underlying causes Associated conditions
Exercise Training
Surgical Therapy: Biventricular Pacing or Cardiac Resynchronization Therapy (CRT) Implantation of Intracardiac Defibrillator Ultrafiltration Cardiac Surgery Left Ventricular Assist Devices (LVADs) Cardiac Transplantation
ACC/AHA Guideline Recommendations Initial and Serial Evaluation of the HF Patient Hospitalized Patient Patients With a Prior MI Sudden Cardiac Death Prevention Surgical/Percutaneous/Transcather Interventional Treatments of HF Patients at high risk for developing heart failure (Stage A) Patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B) Patients with current or prior symptoms of heart failure (Stage C) Patients with refractory end-stage heart failure (Stage D) Coordinating Care for Patients With Chronic HF Quality Metrics/Performance Measures
Implementation of Practice Guidelines
Congestive heart failure end-of-life considerations
Specific Groups: Special Populations Patients who have concomitant disorders Obstructive Sleep Apnea in the Patient with CHF NSTEMI with Heart Failure and Cardiogenic Shock
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Sara Zand, M.D.[2] Seyedmahdi Pahlavani, M.D. [3]

Overview

Management of heart failure is guided by ejection fraction phenotype (HFrEF vs HFmrEF/HFpEF), clinical stage, congestion status, and underlying etiology, with the goals of improving symptoms, reducing hospitalization, and improving survival. Contemporary care prioritizes rapid initiation and optimization of GDMT (foundational 4-drug therapy in HFrEF; SGLT2 inhibitor–centered, comorbidity-driven therapy with selective ARNI/ARB/MRA in HFmrEF/HFpEF) alongside diuretics for relief of congestion. Longitudinal management requires structured reassessment of symptoms, vitals, renal function/electrolytes, and cardiac function to guide titration, add-on therapies, and candidacy for ICD/CRT or structural interventions, with referral for advanced HF therapies when progression occurs. Effective implementation is strengthened by multidisciplinary HF programs, patient education and lifestyle interventions, and coordinated transitions of care.

Management of patients with heart failure with reduced ejection fraction (HFrEF)

The 2022 AHA/ACC/HFSA approach to chronic stage C HFrEF (LVEF ≤40%) emphasizes early initiation of the 4 pillars of guideline-directed medical therapy (GDMT), including ARNi (preferred) or ACEi/ARB, an evidence-based beta-blocker, a MRA in eligible patients, and an SGLT2 inhibitor, alongside diuretics for relief of congestion, with subsequent dose uptitration to target as tolerated. In parallel, patients should be evaluated for device and interventional therapies (e.g., ICD/CRT in appropriate candidates) and referred to an HF specialty team if progressing to advanced/refractory symptoms despite optimized GDMT.

Stage C HFrEF (LVEF ≤40%)

Initial Assessment • Assess congestion/hemodynamics • Fluid overloaded → Diuretics (Class I)

Initiate Foundational GDMT (Class I) • ARNi / ACEi / ARB • Beta-Blocker • MRA • SGLT2i

Titrate GDMT to Target/Max Tolerated Dose • Monitor labs & vitals • Reassess Symptoms & LVEF

LVEF >40% HFimpEF Continue GDMT

LVEF ≤40% Persistent HFrEF

Additional Therapies • African American + NYHA III-IV → Hydralazine-Nitrates • NYHA I-III + LVEF ≤35% + Survival >1 yr → ICD • NYHA II-III + LVEF ≤35% + NSR + LBBB + QRS ≥150 ms → CRT-D • Consider: Ivabradine, Vericiguat, IV Iron

Reassess Symptoms & Status

Symptoms Improved Continue GDMT

Refractory HF (Stage D)

Advanced HF Management • HF Specialty Referral • Durable MCS / LVAD • Cardiac Transplant • Palliative Care

ARNi: Angiotensin Receptor-Neprilysin inhibitor; ACEi: Angiotensin-Converting Enzyme inhibitor; ARB: Angiotensin II Receptor Blocker; MRA: Mineralocorticoid Receptor Antagonist; SGLT2i: Sodium Glucose Cotransporter 2 inhibitors; ICD: Implantable Cardioverter-Defibrillator; CRT-D: Cardiac Resynchronization Therapy with Defibrillator; CRT-P: Cardiac Resynchronization Therapy with Pacemaker; MCS: Mechanical Circulatory Support; LVAD: Left Ventricular Assist Device

The above algorithm is adopted from 2022 AHA/ACC/HFSA Guidelines for Management of Heart Failure

Treatment Algorithm for Guideline-Directed Medical Therapy Including Novel Therapies

Heart failure reduced EF, stage C, treatment

ARNI, ACEI, ARB

For patients with eGFR≥ 30 mL/min/1.73m² or creatinine≤ 2.5 mg/dL in males or ≤2 mg/dL in females or K≤ 5 mEq/L, NYHA 2-4

For patients with eGFR criteria, NYHA 2-4

For patients with persistent volume overload, NYHA 2-4

For symptomatic black patients despite receiving ARNI, betablocker,aldosterone antagonist, SGLT2 inhibitor, NYHA 3-4

For patients with resting HR>70/min despite maximum tolerated betablocker dose, sinus rhythm, NYHA 2-3

Add

Add

Titrate

Add

Add

Aldosterone antagonist

SGLT2 inhibitor

Diuretic agents

Hydralazine + Isosorbide dinitrate

Ivabradine

ARNi: Angiotensin Receptor-Neprilysin inhibitor; ACEi: Angiotensin-Converting Enzyme inhibitor; ARB: Angiotensin II Receptor Blocker; SGLT2i: Sodium Glucose Cotransporter 2 inhibitors

The above algorithm is adopted from 2021 AHA/ACC Guideline

Management of patients with heart failure with preserved ejection fraction (HFrEF)

HFpEF management in the 2022 AHA/ACC/HFSA framework recommends optimizing comorbidities (especially hypertension), using diuretics for congestion, initiating an SGLT2 inhibitor to reduce HF hospitalizations and CV mortality, and selectively adding MRAs, ARBs, or ARNI to reduce hospitalizations, particularly when LVEF is at the lower end of the preserved range.

Symptomatic HF LVEF ≥50%

Diuretics, as needed (Class I)

SGLT2i (Class IIa)

ARNi* (Class IIb)

MRA* (Class IIb)

ARB* (Class IIb)

*Greater benefit in patients with LVEF closer to 50%.

ARNi: Angiotensin Receptor-Neprilysin inhibitor; ACEi: Angiotensin-Converting Enzyme inhibitor; ARB: Angiotensin II Receptor Blocker; MRA: Mineralocorticoid Receptor Antagonist; SGLT2i: Sodium Glucose Cotransporter 2 inhibitors

The above algorithm is adopted from 2022 AHA/ACC/HFSA Guidelines for Management of Heart Failure

Congestive heart failure treatment summary based on 2021 AHA/ACC Guideline

Pathophysiology	Treatment
Renin-angiotensin-aldosterone system	ARNIs/ACEIs/ARBs, aldosterone antagonist
Sympathetic nervous system	Beta-blockers
Natriuretic and other vasodilator peptides	Neprilysin inhibitor (ARNI)
Sodium-glucose cotransporter-2	SGLT2 inhibitors
Balanced vasodilation and oxidative stress modulation	Hydralazine/Isosorbide dinitrate
Elevated heart rate	Betablocker, Ivabradine
Guanylyl cyclase	Soluble guanylyl cyclase stimulator
Relief of congestion	Diuretic
Ventricul;ar arrhythmia	Implantable cardioverter defibrilator
Ventricular dyssynchrony due to conduction abnormalities	Cardiac resynchronization therapy
Mitral regurgitation	Surgical or percutaneous Mitral repair
Reduced aerobic capacity	Aerobic exercise training

The above table is adopted from 2021 AHA/ACC Guideline

Initiation, Titration, and Monitoring of Guideline-Directed Medical Therapy in HFrEF

ACEi / ARB

ACEI / ARB

Initiate if ARNI is not accessible

Initiate dose based on indication

Titrate every 2 weeks to target/max tolerated dose with monitoring of blood pressure, renal function, and potassium

ARNi

ARNI

Initiate ≥36 hours after discontinuing ACEI

Initiate dose based on indication

24/26 mg twice daily if taking enalapril ≤10 mg/day or valsartan ≤160 mg/day

49/51 mg twice daily if taking enalapril >10 mg/day or valsartan >160 mg/day

Reassess in 2 weeks for tolerance, blood pressure, electrolytes, and renal function then titrate to 97/103 mg twice daily

Beta-blocker

Beta blocker

Initiate dose based on indication

Titrate every 2 weeks to target/max tolerated dose with monitoring of heart rate and blood pressure

Mineralocorticoid Receptor Antagonist

MRA

Initiate dose based on indication

Titrate every 2 weeks to target/max tolerated dose with monitoring of electrolytes, renal function, and clinical status

SGLT2 Inhibitor

SGLT2 inhibitor

Initiate dose based on indication

Initiate dapagliflozin if eGFR ≥30 mL/min/1.73 m² or empagliflozin if eGFR ≥20 mL/min/1.73 m²

Diuretic

Diuretic

Initiate loop diuretic dose based on renal function and prior diuretic use

Titrate dose until recovery of congestion with monitoring of blood pressure, renal function, and electrolytes

If persistent congestion on high-dose loop diuretic, consider alternative loop diuretic or add thiazide diuretic

Hydralazine / Isosorbide Dinitrate

Hydralazine / isosorbide dinitrate

Titrate every 2 weeks to target/max tolerated dose with monitoring of blood pressure

Drug-Specific Considerations

Sacubitril/Valsartan	Ivabradine	SGLT2 Inhibitors
Indications HFrEF (EF ≤40%) NYHA class II–IV HF Use with background GDMT Used in place of an ACEI or ARB when feasible	Indications Heart failure with reduced EF (≤35%) On maximum tolerated dose of beta-blocker Sinus rhythm with resting heart rate ≥70 beats/min NYHA class II or III HF	Indications HFrEF (EF ≤40%) with or without diabetes NYHA class II–IV HF Combined with other treatment of heart failure
Contraindications Within 36 hours of ACEI use History of angioedema with or without an ACEI or ARB Pregnancy Lactation (no data) Severe hepatic impairment (Child-Pugh C) Concomitant aliskiren use in patients with diabetes Known hypersensitivity to either ARBs or ARNIs	Contraindications HFpEF Presence of angina with normal EF Hypersensitivity Severe hepatic impairment (Child-Pugh C) Acute decompensated HF Blood pressure <90/50 mm Hg Sick sinus syndrome without a pacemaker Sinoatrial node block 2nd or 3rd degree block without a pacemaker Resting heart rate <60 beats/min Persistent AF or atrial flutter Atrial pacemaker dependence	Contraindications Not approved for use in patients with type I diabetes due to increased risk of diabetic ketoacidosis Known hypersensitivity to drug Lactation (no data) On dialysis
Cautions Renal impairment: Mild-to-moderate (eGFR 30-59 mL/min/1.73 m2): no starting dose adjustment required Severe (eGFR <30 mL/min/1.73 m2): Reduce starting dose to 24/26 mg twice daily Double dose every 2–4 weeks to target maintenance dose of 97/103 mg twice daily as tolerated Hepatic impairment: Mild (Child-Pugh A): no starting dose adjustment required Moderate (Child-Pugh B): Reduce starting dose to 24/26 mg twice daily Double dose every 2–4 weeks to target maintenance dose of 97/103 mg twice daily as tolerated Renal artery stenosis Systolic blood pressure <100 mm Hg Volume depletion	Cautions Sinus node disease Cardiac conduction defects Prolonged QT interval	Cautions For HF care, dapagliflozin in eGFR <30 mL/min/1.73 m2 For HF care, empagliflozin in eGFR <20 mL/min/1.73 m2 Pregnancy Increased risk of mycotic genital infections May contribute to volume depletion, altering diuretic dose if applicable For prevention of ketoacidosis in patients with diabetes: Temporary discontinuation before scheduled surgery Assess patients presenting with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level For prevention of acute kidney injury and renal impairment: Temporarily discontinue in settings of reduced oral intake or fluid losses Urosepsis and pyelonephritis: Evaluate for signs and symptoms of urinary tract infections and treat appropriately Necrotizing fasciitis of the perineum (Fournier’s gangrene): Rare but life-threatening; assess for pain, erythema, swelling, fever, or malaise

The above table adopted from 2021 AHA/ACC Guideline

Ivabradine

Given Betablocker by maximum tolerable dose, sinus rhythm on ECG

Starting dose

Age ≥ 75 years, 2.5 mg twice daily with food

Age <75 years, 5 mg twice daily with food

Evaluation of heart rate in 2-4 weeks

Heart rate < 50 beats /min or symptoms of bradycardia

Heart rate 50-60 beats/ min

Heart rate>60 beats /min

Reduced dose 2.5 mg twice daily with food, or discontinued if already on 2.5 mg twice daily

Maintaing current dose with monitoring heart rate

Increased dose by 2.5 mg twice daily until maximum dose of 7.5 mg twice daily, monitoring heart rate