What is the recommended management of heart failure?

Management of Heart Failure

All patients with heart failure and reduced ejection fraction (HFrEF, LVEF ≤40%) should receive four foundational medication classes initiated simultaneously: ACE inhibitors (or ARNi), beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, as this combination reduces mortality and hospitalization. 1

Pharmacological Management for HFrEF

Step 1: Initiate Foundational Quadruple Therapy

ACE Inhibitors (or ARNi)

• Start ACE inhibitors immediately in all patients with reduced left ventricular systolic function, beginning with low doses and gradually titrating to target maintenance doses proven effective in clinical trials 2, 1, 3
• Target doses from major trials: lisinopril 20-35 mg daily, enalapril 10-20 mg twice daily, or ramipril 5-10 mg daily 1
• Before initiating, review and potentially reduce diuretic doses for 24 hours to avoid excessive hypotension 2, 1, 3
• Consider starting treatment in the evening when supine to minimize potential negative effects on blood pressure, though supervision for several hours with blood pressure monitoring is advisable if initiated in the morning 2
• Sacubitril-valsartan (ARNi) is recommended as a replacement for ACE inhibitors in ambulatory patients with HFrEF who remain symptomatic despite optimal treatment with an ACE inhibitor, beta-blocker, and MRA 3

Beta-Blockers

• Initiate in all stable patients with mild, moderate, and severe heart failure (NYHA class II-IV) who are already on ACE inhibitors and diuretics 2, 1, 3
• Evidence-based beta-blockers with proven mortality benefit: bisoprolol, metoprolol succinate CR, carvedilol, or nebivolol 1
• Start with very low doses and double every 1-2 weeks if tolerated 1
• Beta-blockers reduce mortality by at least 20% and decrease hospitalizations 1
• In patients with LV systolic dysfunction following acute myocardial infarction, long-term beta-blockade is recommended in addition to ACE inhibition to reduce mortality 2

Mineralocorticoid Receptor Antagonists (MRAs)

• Add spironolactone or eplerenone for patients who remain symptomatic (NYHA Class III-IV) despite ACE inhibitor and beta-blocker therapy to reduce mortality and hospitalization 2, 1, 3
• Start 1-week low-dose administration, check serum potassium and creatinine after 5-7 days and titrate accordingly 2
• Recheck every 5-7 days until potassium values are stable 2

SGLT2 Inhibitors

• Initiate early in all HFrEF patients regardless of diabetes status to reduce cardiovascular death and heart failure hospitalization 1
• SGLT2 inhibitors are now recommended for treatment of heart failure across the entire left ventricular ejection fraction spectrum 4

Step 2: Diuretic Therapy for Symptom Management

Initial Diuretic Treatment

• Loop diuretics or thiazides should always be administered in addition to an ACE inhibitor 2, 1, 3
• If GFR <30 ml/min, do not use thiazides except as therapy prescribed synergistically with loop diuretics 2
• Diuretics result in rapid improvement of dyspnea and increased exercise tolerance 2

Insufficient Response

• Increase dose of diuretic 2
• Combine loop diuretics and thiazides 2
• With persistent fluid retention: administer loop diuretics twice daily 2
• In severe chronic heart failure add metolazone with frequent measurement of creatinine and electrolytes 2

Step 3: Additional Therapies for Persistent Symptoms

Digoxin

• In atrial fibrillation with any degree of symptomatic heart failure, digoxin is indicated to slow ventricular rate, thereby improving ventricular function and symptoms 2
• A combination of digoxin and beta-blockade appears superior to either agent alone 2
• In sinus rhythm, digoxin is recommended to improve clinical status of patients with persisting heart failure symptoms due to left ventricular systolic dysfunction despite ACE inhibitor and diuretic treatment 2
• Usual daily dose: 0.25-0.375 mg if serum creatinine is in normal range (in elderly 0.125-0.25 mg) 2

Hydralazine-Isosorbide Dinitrate

• The combination is appropriate for African Americans with HFrEF who remain symptomatic despite concomitant use of ACE inhibitor (or ARB), beta blockers, and MRA 2
• Might be considered as a therapeutic option in patients intolerant of ACE inhibitors or ARBs, especially those with renal insufficiency, though benefit is uncertain 2

Vericiguat

• Patients experiencing an episode of worsening heart failure might require vericiguat as a fifth drug 4

Critical Monitoring Parameters

Laboratory and Clinical Monitoring

• Check blood pressure, renal function, and electrolytes 1-2 weeks after each dose increment, at 3 months, and subsequently at 6-month intervals 2, 1, 3
• If renal function deteriorates substantially during ACE inhibitor initiation, stop treatment 2

Management of HFpEF (LVEF ≥50%)

SGLT2 Inhibitors

• SGLT2 inhibitors are recommended as first-line therapy for HFpEF to reduce heart failure hospitalizations and cardiovascular death 2, 4
• Greater benefit is observed in patients with LVEF closer to 50% 2

Diuretics

• Essential for symptomatic treatment when fluid overload is present 2, 3

ARNi (Sacubitril-Valsartan)

• May be considered, though benefit is greater in patients with LVEF closer to 50% 2

Mineralocorticoid Receptor Antagonists

• May provide benefit, particularly in patients with LVEF closer to 50% 2

Semaglutide

• In obese patients with HFpEF, semaglutide 2.4 mg once weekly administered for 1 year decreased body weight and significantly improved quality of life and 6-minute walk distance 4

Device Therapy

Implantable Cardioverter Defibrillators (ICDs)

• Recommended for primary prevention in symptomatic HF (NYHA Class II-III) with LVEF ≤35% despite ≥3 months of optimal medical therapy in patients with ischemic heart disease or dilated cardiomyopathy 1, 3
• Indicated for secondary prevention in patients who survived ventricular arrhythmia causing hemodynamic instability 1, 3
• ICD implantation is not recommended within 40 days of an MI as it does not improve prognosis 3

Cardiac Resynchronization Therapy (CRT)

• Recommended for symptomatic heart failure patients in sinus rhythm with QRS duration ≥150 msec, LBBB QRS morphology, and LVEF ≤35% 1, 3

Non-Pharmacological Management

Patient Education

• Explain what heart failure is, why symptoms occur, causes of heart failure, how to recognize symptoms, and what to do if symptoms occur 2, 1, 3
• Teach self-weighing to monitor fluid status 2, 1
• Emphasize importance of adhering to pharmacological and non-pharmacological prescriptions 2, 1
• Advise to refrain from smoking; use of nicotine replacement therapies 2

Physical Activity and Exercise

• Daily physical activity should be encouraged in stable patients to prevent muscle deconditioning and improve exercise tolerance 2, 1, 3
• Exercise training programs are beneficial for stable NYHA II-III patients 2, 1
• Rest is not encouraged in stable conditions 2

Dietary Modifications

• Control sodium intake when necessary, especially in patients with severe heart failure 2, 1, 3
• Avoid excessive fluid intake in severe heart failure 2, 1, 3
• Avoid excessive alcohol intake 2

Critical Pitfalls and Contraindications

Medications to Avoid

• Avoid diltiazem or verapamil in patients with HFrEF as they increase the risk of heart failure worsening 1, 3
• Avoid non-steroidal anti-inflammatory drugs (NSAIDs) 2, 1
• Avoid potassium-sparing diuretics during initiation of ACE inhibitor therapy 2, 1
• Avoid the combination of an ACE inhibitor, ARB, and MRA due to increased risk of renal dysfunction and hyperkalemia 1, 3

Common Pitfalls

• Avoid excessive diuresis before ACE inhibitor treatment; reduce or withhold diuretics for 24 hours before initiation 2, 1, 3
• Do not delay initiation of all four foundational therapies—they should be started simultaneously at low doses and titrated up, rather than waiting to achieve target dosing of one before starting another 1
• Evidence-based heart failure medications should be continued during hospitalization unless the patient is hemodynamically unstable 5