17:I[462708,["/_next/static/chunks/3yo3kiro3bmlp.js","/_next/static/chunks/3vr2wvd8f2efb.js","/_next/static/chunks/2vtmb68_vu-9t.js","/_next/static/chunks/2s8mt6_8wrpfo.js","/_next/static/chunks/3vkulz2i3l61y.js","/_next/static/chunks/1cqw2i1silz0i.js","/_next/static/chunks/14dbm3lm_t629.js","/_next/static/chunks/335_v2mb569ld.js","/_next/static/chunks/3ykn5ops9bft5.js","/_next/static/chunks/3cmavum774kjt.js","/_next/static/chunks/3th-0-a2xf9qs.js","/_next/static/chunks/0p0xpwde6kzmv.js","/_next/static/chunks/401-sxxnzbtf_.js","/_next/static/chunks/0wywtv698a1v0.js","/_next/static/chunks/2botzqwpnrzyj.js"],"ArticleReader"] 18:T6991,## Summary Heart failure with reduced ejection fraction (HFrEF) is a clinical heart-failure syndrome with **left ventricular ejection fraction (LVEF) ≤40%** in the current U.S. framework. A low LVEF alone is not sufficient: confirm symptoms/signs of heart failure, identify the cause, define congestion and perfusion, and detect comorbidities or reversible triggers that alter management.[1] For most adults with chronic symptomatic HFrEF, the disease-modifying foundation is **four therapies started early and in parallel at tolerated doses**: an angiotensin receptor-neprilysin inhibitor (ARNI) or alternative renin-angiotensin system blocker, an evidence-based beta-blocker, a mineralocorticoid receptor antagonist (MRA), and an SGLT2 inhibitor.[1,2] The 2024 ACC pathway emphasizes establishing all four classes and titrating toward maximally tolerated or target doses within approximately **3 months** when feasible rather than maximizing one drug before adding the others.[2] Common target doses include sacubitril/valsartan **97/103 mg twice daily**, carvedilol **25–50 mg twice daily**, metoprolol succinate **200 mg daily**, bisoprolol **10 mg daily**, spironolactone **25–50 mg daily**, and eplerenone **50 mg daily**. Dapagliflozin and empagliflozin are each used at **10 mg once daily** without titration for HFrEF.[1,2] Use an MRA when **eGFR >30 mL/min/1.73 m² and potassium <5.0 mmol/L**. If potassium cannot be maintained **<5.5 mmol/L**, stop the MRA.[1] Sacubitril/valsartan must not be given with an ACE inhibitor; allow a **36-hour washout** after the last ACE-inhibitor dose. SGLT2 inhibitors reduce heart-failure events in HFrEF regardless of diabetes status.[1,4,5] Loop diuretics relieve congestion but do not replace disease-modifying therapy. Treat to clinical euvolemia, then use the lowest effective maintenance dose. A modest creatinine rise during effective decongestion or initiation of renin-angiotensin system therapy should be interpreted in context rather than prompting automatic withdrawal of therapies with proven outcome benefit.[1,3] Hospitalization for decompensated HFrEF is an opportunity to **decongest and establish missing core therapies before discharge once hemodynamically stable**. The 2024 ACC inpatient pathway specifically emphasizes SGLT2 inhibitor use and initiation of the four foundational classes during hospitalization when possible.[3] Primary-prevention ICD therapy is recommended for appropriately selected patients with **LVEF ≤35%**, NYHA II–III symptoms despite chronic guideline-directed therapy, and expected meaningful survival >1 year. CRT has its strongest indication in patients with **LVEF ≤35%, sinus rhythm, left bundle-branch block, QRS ≥150 ms, and NYHA II–III or ambulatory IV symptoms** despite treatment.[1] When LVEF improves above 40% after prior HFrEF, continue HFrEF disease-modifying therapy unless a compelling contraindication develops. Recovery represents remission rather than proof that the underlying cardiomyopathy is cured; withdrawal can precipitate relapse.[1,8] > **Clinical pearl:** In a stable patient, low tolerated doses across all four core classes usually provide more comprehensive disease modification than high doses of one or two classes while the other pathways remain untreated.[2] ## Definition and phenotype Current U.S. categories are:[1] - **HFrEF:** LVEF ≤40%; - **heart failure with mildly reduced EF:** LVEF 41–49% with evidence supporting heart failure; - **heart failure with preserved EF:** LVEF ≥50% with evidence supporting heart failure; - **heart failure with improved EF:** prior LVEF ≤40% followed by LVEF >40%. LVEF has measurement variability and changes with loading conditions, rhythm, revascularization, valve intervention, and treatment. Interpret the number alongside clinical trajectory and imaging quality. ## Etiology HFrEF is a syndrome. The cause should be actively defined because several etiologies require additional therapy. | Cause | Clues | Key next actions | |---|---|---| | Ischemic cardiomyopathy | Prior MI, angina, coronary risk, regional wall-motion abnormality | Define coronary anatomy/ischemia when revascularization could change management | | Dilated/genetic cardiomyopathy | Younger age, family cardiomyopathy or sudden death, conduction disease | Cardiac MRI; 3-generation family history; genetic counseling/testing when appropriate | | Hypertensive cardiomyopathy | Long-standing hypertension, LV hypertrophy | Optimize pressure and assess competing causes | | Valvular disease | Murmur, chamber remodeling, pulmonary hypertension | Full valve assessment; structural/surgical review when severe | | Myocarditis | Recent inflammatory illness, chest pain, arrhythmia | Cardiac MRI; myocarditis pathway when appropriate | | Tachycardia-mediated cardiomyopathy | Persistent AF/flutter/SVT or high ectopic burden | Quantify rhythm burden and pursue rate/rhythm control | | Alcohol or stimulant exposure | Heavy alcohol, cocaine, methamphetamine | Remove exposure and treat substance-use disorder | | Cancer therapy | Anthracycline, HER2-directed or other cardiotoxic exposure | Cardio-oncology review | | Endocrine/metabolic | Thyroid disease, iron overload, major nutritional deficiency | Cause-directed laboratory testing | | Infiltrative/inflammatory | Amyloid, sarcoidosis, hemochromatosis clues | Cardiac MRI and disease-specific testing | | Peripartum cardiomyopathy | Late pregnancy or postpartum onset | Cardio-obstetric care and pregnancy-compatible therapy | ## Pathophysiology Reduced systolic function lowers forward output and raises intracardiac filling pressures. Compensatory activation of the sympathetic nervous system, renin-angiotensin-aldosterone system, vasopressin, renal sodium retention, and vasoconstriction initially supports perfusion but subsequently promotes: - ventricular dilation and adverse remodeling; - myocardial fibrosis; - increased afterload; - sodium and water retention; - functional mitral regurgitation; - atrial and ventricular arrhythmia; - cardiorenal dysfunction; - sudden cardiac death. The core drug classes target different components of this biology, which is why combined therapy is more effective than sequential reliance on a single pathway.[1,2] ## Clinical assessment ### Symptoms - exertional dyspnea; - orthopnea or paroxysmal nocturnal dyspnea; - fatigue and reduced exercise tolerance; - peripheral edema; - abdominal distention or early satiety; - rapid weight gain from fluid retention; - nocturia; - presyncope or syncope; - cachexia in advanced disease. ### Bedside findings Document: - heart rate and rhythm; - blood pressure and orthostatic symptoms; - jugular venous pressure and hepatojugular reflux; - pulmonary crackles or pleural effusion; - third heart sound; - murmurs; - peripheral edema; - hepatomegaly or ascites; - cool extremities, delayed capillary refill, narrow pulse pressure; - frailty and muscle wasting. ### Congestion and perfusion | Profile | Perfusion | Congestion | Practical implication | |---|---|---|---| | Warm/dry | Adequate | Absent | Desired stable state | | Warm/wet | Adequate | Present | Most common decompensated profile; decongest | | Cold/wet | Reduced | Present | High risk; assess for shock and advanced HF | | Cold/dry | Reduced | Absent | Consider low output, overdiuresis, or advanced disease | ## Red flags and urgent escalation Hospital-level care is required for: - hypotension with altered mentation, oliguria, lactate elevation, cool/mottled skin, or other shock features; - severe respiratory distress or hypoxemia; - acute coronary syndrome; - sustained ventricular tachycardia or ventricular fibrillation; - high-grade bradyarrhythmia; - recurrent ICD shocks; - acute severe valve regurgitation or another mechanical complication; - syncope with suspected malignant arrhythmia; - rapidly worsening renal or hepatic dysfunction with congestion or low output. ## Diagnostic work-up ### Baseline studies Typical evaluation includes:[1] - 12-lead ECG; - CBC; - sodium, potassium, bicarbonate, urea/BUN, creatinine/eGFR; - glucose and HbA1c; - liver chemistry; - TSH; - ferritin and transferrin saturation; - urinalysis and urine albumin:creatinine ratio when kidney disease is relevant; - BNP or NT-proBNP; - chest radiography when pulmonary congestion or another thoracic process is possible; - transthoracic echocardiography. ### Natriuretic peptides BNP and NT-proBNP support diagnosis and prognosis. Concentrations can be higher with age, atrial fibrillation, and chronic kidney disease and lower than expected with obesity. After sacubitril/valsartan initiation, **NT-proBNP is easier to interpret serially** because neprilysin inhibition directly affects BNP metabolism. ### Echocardiography Define: - LVEF and LV dimensions; - RV size and function; - valve disease; - estimated pulmonary pressure; - regional wall-motion abnormalities; - pericardial disease; - filling-pressure and diastolic parameters. Repeat imaging after adequate treatment when recovery would change ICD/CRT or valve decisions, and whenever a meaningful clinical change suggests new structural disease. ### Cardiac MRI Use when tissue characterization or anatomy may clarify myocarditis, infiltrative disease, sarcoidosis, ischemic versus nonischemic scar, arrhythmic substrate, or uncertain echocardiographic EF. ### Ischemic assessment Evaluate for coronary disease when ischemia is plausible, the cause remains uncertain, or revascularization could alter prognosis or symptoms. Choose coronary CT angiography, stress imaging, or invasive angiography according to pretest probability, kidney function, symptoms, and revascularization intent. ## Initial management priorities 1. Determine whether the patient is stable or acutely decompensated. 2. Establish whether congestion is present and create a decongestion plan. 3. Start the four disease-modifying classes promptly when hemodynamically and biochemically safe. 4. Identify and treat the cause and reversible triggers. 5. Arrange early laboratory and clinical follow-up after each therapy change. 6. Reassess LVEF after adequate therapy if device candidacy is possible. ## Four core disease-modifying therapies ### Dosing and monitoring | Therapy | Typical starting dose | Target dose | Key monitoring | |---|---:|---:|---| | Sacubitril/valsartan | 24/26 or 49/51 mg twice daily | 97/103 mg twice daily | BP, potassium, creatinine/eGFR | | Carvedilol | 3.125 mg twice daily | 25 mg twice daily; 50 mg twice daily in selected larger patients | HR, BP, congestion | | Metoprolol succinate | 12.5–25 mg daily | 200 mg daily | HR, BP, congestion | | Bisoprolol | 1.25 mg daily | 10 mg daily | HR, BP, congestion | | Spironolactone | 12.5–25 mg daily | 25–50 mg daily | Potassium, creatinine/eGFR | | Eplerenone | 25 mg daily | 50 mg daily | Potassium, creatinine/eGFR | | Dapagliflozin | 10 mg daily | 10 mg daily | Volume status, renal trajectory, genital infection, ketoacidosis risk | | Empagliflozin | 10 mg daily | 10 mg daily | Volume status, renal trajectory, genital infection, ketoacidosis risk | Use jurisdiction-specific labeling for renal thresholds and dose restrictions.[1,2] ### ARNI and alternative renin-angiotensin therapy For symptomatic chronic HFrEF, ARNI is preferred when feasible. Sacubitril/valsartan reduced cardiovascular death and heart-failure hospitalization compared with enalapril in PARADIGM-HF.[1,6] If ARNI cannot be used, an ACE inhibitor or ARB remains appropriate when tolerated. Safety rules: - never combine ARNI with an ACE inhibitor; - allow **36 hours** after stopping an ACE inhibitor before starting sacubitril/valsartan; - avoid ARNI when prior angioedema creates a labeling contraindication; - monitor blood pressure, potassium, and kidney function. ### Evidence-based beta-blocker Use carvedilol, metoprolol succinate, or bisoprolol.[1] Start when the patient is clinically stable and not in cardiogenic shock. Chronic beta-blocker therapy is usually continued during decompensation unless shock, severe bradycardia, or another clear contraindication develops. New initiation or dose increase is best after stabilization and adequate decongestion. ### Mineralocorticoid receptor antagonist Use spironolactone or eplerenone when:[1] - **eGFR >30 mL/min/1.73 m²**, and - **potassium <5.0 mmol/L**. Check potassium and kidney function soon after initiation or dose increase and more frequently with CKD, diabetes, older age, or interacting drugs. If potassium cannot be maintained **<5.5 mmol/L**, discontinue the MRA.[1] ### SGLT2 inhibitor Dapagliflozin and empagliflozin reduce worsening-HF events in HFrEF with or without diabetes.[4,5] Practical points: - use **10 mg once daily** without titration; - expect a small early eGFR dip in some patients; - reassess loop-diuretic dose if volume depletion develops; - counsel about genital mycotic infection; - temporarily withhold during prolonged fasting, major surgery, or severe acute illness when ketoacidosis risk rises; - investigate nausea, abdominal pain, unexplained acidosis, or ketosis even when glucose is not markedly elevated. ## Sequencing and titration The 2024 ACC pathway recommends rapid establishment of all four core therapies and titration over roughly **3 months** when feasible.[2] | Clinical issue | Practical approach | |---|---| | Low-normal BP | Preserve SGLT2 inhibitor and MRA when possible; use lower ARNI/beta-blocker doses; remove nonessential vasodilators | | Tachycardia | Establish evidence-based beta-blocker once congestion and perfusion permit | | Hyperkalemia risk | Review potassium intake/drugs, optimize diuretic and SGLT2 strategy, intensify laboratory monitoring | | eGFR near MRA threshold | Use other core therapies within labeling; add MRA only when safety criteria are met | | Marked congestion | Decongest while maintaining or introducing disease-modifying therapy as stability permits | | Recent hospitalization | Fill GDMT gaps before discharge and arrange early post-discharge titration | > **Current practice:** Do not wait for a beta-blocker or ARNI to reach target before adding an SGLT2 inhibitor or MRA. Several therapies begin providing benefit early.[2,3] ## Diuretics and congestion Loop diuretics are used to achieve and maintain euvolemia. Common oral starting doses in diuretic-naive outpatients include: - furosemide **20–40 mg once or twice daily**; - torsemide **10–20 mg daily**; - bumetanide **0.5–1 mg once or twice daily**. Adjust according to prior exposure, kidney function, gut edema, response, and congestion. In acute decompensation, IV loop diuretics are usually required. Monitor: - dyspnea and orthopnea; - weight trajectory when useful; - JVP and edema; - urine output in acute care; - sodium, potassium, magnesium; - creatinine/eGFR. For inadequate loop response, reassess dose, absorption, adherence, perfusion, and renal function. Sequential nephron blockade with a thiazide-type diuretic can be used selectively with close electrolyte monitoring. The treatment target is **clinical decongestion**, not an unchanged creatinine value at the cost of persistent volume overload.[3] ## Additional therapy for selected patients ### Hydralazine plus isosorbide dinitrate A fixed-dose combination is recommended in self-identified Black patients with NYHA III–IV HFrEF receiving optimal therapy and may be considered when ARNI/ACE inhibitor/ARB cannot be used.[1] Typical fixed-dose treatment starts at **20 mg isosorbide dinitrate/37.5 mg hydralazine three times daily** and targets **40/75 mg three times daily** as tolerated.[1] ### Ivabradine Consider in selected stable symptomatic patients with: - LVEF ≤35%; - sinus rhythm; - resting heart rate ≥70/min; - maximally tolerated evidence-based beta-blocker.[1] Typical starting dose is **5 mg twice daily**, adjusted toward **7.5 mg twice daily** according to heart rate, age, and conduction status. ### Vericiguat May be considered in selected high-risk patients with recent worsening HFrEF despite optimized background therapy. A common titration is **2.5 mg daily → 5 mg daily → 10 mg daily** as tolerated.[1,2] ### Digoxin May reduce recurrent hospitalization in selected symptomatic HFrEF or assist rate control when alternatives are inadequate. Use conservatively in kidney dysfunction, older age, low body mass, hypokalemia, and interacting drug regimens. Typical maintenance is **0.125–0.25 mg daily**, often lower with CKD or frailty. When a chronic level is checked for HFrEF, a concentration around **0.5 to <0.9 ng/mL** is generally targeted.[1] ## Iron deficiency Check ferritin and transferrin saturation in symptomatic HFrEF. A commonly used definition is:[1] - ferritin **<100 ng/mL**; or - ferritin **100–300 ng/mL with transferrin saturation <20%**. IV iron is reasonable in selected symptomatic patients with documented iron deficiency to improve functional status and quality of life. Choice of preparation and repeat dosing follow local protocols and current labeling. Oral iron often performs poorly for functional iron deficiency in HFrEF. ## Atrial fibrillation and ventricular arrhythmia Atrial fibrillation can be a cause, consequence, or precipitant of HFrEF. Management includes: - anticoagulation according to thromboembolic risk; - rate control; - rhythm control when symptoms, tachycardia-mediated cardiomyopathy, or HF trajectory support it; - catheter ablation in appropriate patients; - correction of electrolyte, ischemic, and thyroid triggers. Sustained ventricular arrhythmia or recurrent ICD shocks requires urgent electrophysiology/cardiology review. ## Device therapy ### Implantable cardioverter-defibrillator Primary-prevention ICD is recommended for appropriate patients with:[1] - **LVEF ≤35%**; - NYHA II–III symptoms on chronic disease-modifying therapy; - expected meaningful survival >1 year. It is also recommended in selected post-MI patients with LVEF ≤30% and NYHA I symptoms after the appropriate post-infarction interval.[1] Avoid premature implantation before adequate recovery time after a new cardiomyopathy, revascularization, or major therapy optimization unless a secondary-prevention indication exists. ### Cardiac resynchronization therapy The strongest indication is:[1] - LVEF ≤35%; - sinus rhythm; - left bundle-branch block; - QRS ≥150 ms; - NYHA II–III or ambulatory IV symptoms despite therapy. Benefit is less consistent with non-left-bundle morphology or narrower QRS. CRT should not be used solely for QRS <120 ms.[1] ## Secondary mitral regurgitation Functional mitral regurgitation can improve with reverse remodeling. Before transcatheter or surgical valve intervention: 1. establish all tolerated core HFrEF therapies; 2. achieve euvolemia; 3. treat ischemia when indicated; 4. use CRT when criteria are met; 5. reassess regurgitation severity and anatomy. Persistent severe symptomatic secondary mitral regurgitation despite optimization warrants structural-heart review. ## Acute decompensated HFrEF ### Immediate priorities - identify precipitant and competing emergencies; - assess perfusion and shock; - give IV loop diuretic for clinically important congestion; - provide oxygen only when hypoxemic; - treat acute ischemia, infection, arrhythmia, hypertensive crisis, or other trigger; - avoid routine inotrope use unless low-output shock or another specific indication exists.[3] ### Disease-modifying therapy during hospitalization The 2024 ACC pathway emphasizes filling gaps in the four foundational therapies during hospitalization when the patient is stable enough.[3] A practical sequence is: 1. decongest and stabilize; 2. continue chronic disease-modifying therapy unless a real contraindication develops; 3. initiate SGLT2 inhibitor early when eligible; 4. add or optimize ARNI/ACE inhibitor/ARB, evidence-based beta-blocker, and MRA as hemodynamics and renal/potassium status permit; 5. define the outpatient titration plan before discharge. Patients with chronic class IV symptoms, marginal perfusion, or recent inotrope dependence may not tolerate standard titration and should receive advanced-HF input.[3] ### Discharge readiness Before discharge, confirm: - adequate decongestion or a clearly documented residual-volume strategy; - stable blood pressure and renal/electrolyte trajectory; - oral diuretic plan; - current and planned core therapies; - laboratory follow-up; - medication access and adherence barriers; - early post-discharge clinical review; - device/advanced-HF referral when indicated. ## Monitoring after therapy changes ### ARNI, ACE inhibitor, or ARB Track blood pressure, potassium, creatinine/eGFR, dizziness, and angioedema symptoms. ### MRA Check potassium and kidney function early after initiation or dose change and repeatedly during titration in high-risk patients. ### Beta-blocker Track resting heart rate, blood pressure, symptoms of bradycardia, and congestion. ### SGLT2 inhibitor Track volume status, renal trajectory, genital infection, and ketoacidosis risk during acute illness. ### Outpatient review Document: - NYHA functional status; - recent hospitalization or urgent IV diuretic use; - weight and congestion trajectory; - blood pressure and heart rate; - medication access and adherence; - kidney function and potassium; - iron status when indicated; - rhythm; - need for repeat echocardiography; - device eligibility; - goals of care in advanced disease. ## Heart failure with improved EF When a patient with prior LVEF ≤40% improves to >40%, continue HFrEF disease-modifying therapy unless a compelling contraindication exists.[1] TRED-HF demonstrated frequent relapse after withdrawal of therapy in recovered dilated cardiomyopathy.[8] Do not relabel recovery as cure without considering the underlying etiology and relapse risk. ## Advanced heart-failure referral Refer early when there is: - repeated HF hospitalization; - escalating loop-diuretic requirement; - persistent NYHA III–IV symptoms despite therapy; - hypotension preventing core therapy; - progressive renal or hepatic dysfunction; - recurrent ventricular arrhythmia or ICD shocks; - intolerance of several disease-modifying classes; - need for IV inotropes; - persistent low-output signs; - cardiac cachexia; - potential candidacy for transplant or durable mechanical circulatory support. Late referral can eliminate options when frailty, pulmonary vascular disease, kidney dysfunction, or liver dysfunction becomes irreversible. ## Special populations ### Chronic kidney disease and hyperkalemia CKD should not automatically lead to under-treatment. Use therapies within current renal thresholds, monitor closely, avoid NSAIDs, and distinguish a small expected hemodynamic eGFR change from progressive kidney injury. ### Low blood pressure Asymptomatic low blood pressure does not always require reducing all disease-modifying therapy. First review: - excess diuretic in a euvolemic patient; - nitrates or other nonessential vasodilators; - alpha-blockers or other pressure-lowering drugs without HFrEF outcome benefit; - dehydration. Preserve low doses across multiple outcome-improving classes when possible.[2] ### Pregnancy potential ACE inhibitors, ARBs, ARNIs, MRAs, and SGLT2 inhibitors are generally avoided during pregnancy. Peripartum cardiomyopathy requires coordinated cardio-obstetric management and pregnancy-compatible vasodilator, beta-blocker, and diuretic strategies. ### Older adults and frailty Use the same disease-modifying framework while accounting for orthostasis, kidney function, falls, cognition, polypharmacy, nutrition, and goals of care. Start lower when needed but do not treat age alone as a contraindication to beneficial therapy. ## Prognosis Prognosis depends on etiology, LVEF, symptoms, natriuretic peptide burden, kidney function, congestion, blood pressure, arrhythmia, frailty, recurrent worsening events, and response to therapy. A heart-failure hospitalization is a major prognostic event and should trigger a systematic review of: - all four core therapies; - dose and adherence; - congestion control; - rhythm; - ischemia; - valve disease; - device candidacy; - advanced-HF referral. ## Related library topics - [Acute Decompensated Heart Failure](acute-decompensated-heart-failure.md) - [Heart Failure With Preserved Ejection Fraction](heart-failure-with-preserved-ejection-fraction.md) - [Atrial Fibrillation](atrial-fibrillation.md) - [Acute Coronary Syndrome](acute-coronary-syndrome.md) - [Mitral Regurgitation in Adults](mitral-regurgitation-in-adults.md) - [Chronic Kidney Disease](../nephrology/chronic-kidney-disease.md) - [Hyperkalemia](../nephrology/hyperkalemia.md) ## References 1. Heidenreich PA, Bozkurt B, Aguilar D, et al. **2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.** *Circulation.* 2022;145:e895-e1032. doi:10.1161/CIR.0000000000001063. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001063 2. Maddox TM, Januzzi JL Jr, Allen LA, et al. **2024 ACC Expert Consensus Decision Pathway for Treatment of Heart Failure With Reduced Ejection Fraction.** *J Am Coll Cardiol.* 2024;83(15):1444-1488. doi:10.1016/j.jacc.2023.12.024. PMID:38466244. https://doi.org/10.1016/j.jacc.2023.12.024 3. Hollenberg SM, Stevenson LW, Ahmad T, et al. **2024 ACC Expert Consensus Decision Pathway on Clinical Assessment, Management, and Trajectory of Patients Hospitalized With Heart Failure Focused Update.** *J Am Coll Cardiol.* 2024;84(13):1241-1267. doi:10.1016/j.jacc.2024.06.002. PMID:39127954. https://doi.org/10.1016/j.jacc.2024.06.002 4. McMurray JJV, Solomon SD, Inzucchi SE, et al. **Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction.** *N Engl J Med.* 2019;381:1995-2008. doi:10.1056/NEJMoa1911303. PMID:31535829. https://doi.org/10.1056/NEJMoa1911303 5. Packer M, Anker SD, Butler J, et al. **Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure.** *N Engl J Med.* 2020;383:1413-1424. doi:10.1056/NEJMoa2022190. PMID:32865377. https://doi.org/10.1056/NEJMoa2022190 6. McMurray JJV, Packer M, Desai AS, et al. **Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure.** *N Engl J Med.* 2014;371:993-1004. doi:10.1056/NEJMoa1409077. PMID:25176015. https://doi.org/10.1056/NEJMoa1409077 7. Pitt B, Zannad F, Remme WJ, et al. **The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure.** *N Engl J Med.* 1999;341:709-717. doi:10.1056/NEJM199909023411001. PMID:10471456. https://doi.org/10.1056/NEJM199909023411001 8. Halliday BP, Wassall R, Lota AS, et al. **Withdrawal of Pharmacological Treatment for Heart Failure in Patients with Recovered Dilated Cardiomyopathy (TRED-HF).** *Lancet.* 2019;393:61-73. doi:10.1016/S0140-6736(18)32484-X. PMID:30429050. https://pubmed.ncbi.nlm.nih.gov/30429050/19:T69d5,## Summary Heart failure with reduced ejection fraction (HFrEF) is a clinical heart-failure syndrome with **left ventricular ejection fraction (LVEF) ≤40%** in the current U.S. framework. A low LVEF alone is not sufficient: confirm symptoms/signs of heart failure, identify the cause, define congestion and perfusion, and detect comorbidities or reversible triggers that alter management.[1] For most adults with chronic symptomatic HFrEF, the disease-modifying foundation is **four therapies started early and in parallel at tolerated doses**: an angiotensin receptor-neprilysin inhibitor (ARNI) or alternative renin-angiotensin system blocker, an evidence-based beta-blocker, a mineralocorticoid receptor antagonist (MRA), and an SGLT2 inhibitor.[1,2] The 2024 ACC pathway emphasizes establishing all four classes and titrating toward maximally tolerated or target doses within approximately **3 months** when feasible rather than maximizing one drug before adding the others.[2] Common target doses include sacubitril/valsartan **97/103 mg twice daily**, carvedilol **25–50 mg twice daily**, metoprolol succinate **200 mg daily**, bisoprolol **10 mg daily**, spironolactone **25–50 mg daily**, and eplerenone **50 mg daily**. Dapagliflozin and empagliflozin are each used at **10 mg once daily** without titration for HFrEF.[1,2] Use an MRA when **eGFR >30 mL/min/1.73 m² and potassium <5.0 mmol/L**. If potassium cannot be maintained **<5.5 mmol/L**, stop the MRA.[1] Sacubitril/valsartan must not be given with an ACE inhibitor; allow a **36-hour washout** after the last ACE-inhibitor dose. SGLT2 inhibitors reduce heart-failure events in HFrEF regardless of diabetes status.[1,4,5] Loop diuretics relieve congestion but do not replace disease-modifying therapy. Treat to clinical euvolemia, then use the lowest effective maintenance dose. A modest creatinine rise during effective decongestion or initiation of renin-angiotensin system therapy should be interpreted in context rather than prompting automatic withdrawal of therapies with proven outcome benefit.[1,3] Hospitalization for decompensated HFrEF is an opportunity to **decongest and establish missing core therapies before discharge once hemodynamically stable**. The 2024 ACC inpatient pathway specifically emphasizes SGLT2 inhibitor use and initiation of the four foundational classes during hospitalization when possible.[3] Primary-prevention ICD therapy is recommended for appropriately selected patients with **LVEF ≤35%**, NYHA II–III symptoms despite chronic guideline-directed therapy, and expected meaningful survival >1 year. CRT has its strongest indication in patients with **LVEF ≤35%, sinus rhythm, left bundle-branch block, QRS ≥150 ms, and NYHA II–III or ambulatory IV symptoms** despite treatment.[1] When LVEF improves above 40% after prior HFrEF, continue HFrEF disease-modifying therapy unless a compelling contraindication develops. Recovery represents remission rather than proof that the underlying cardiomyopathy is cured; withdrawal can precipitate relapse.[1,8] > **Clinical pearl:** In a stable patient, low tolerated doses across all four core classes usually provide more comprehensive disease modification than high doses of one or two classes while the other pathways remain untreated.[2] ## Definition and phenotype Current U.S. categories are:[1] - **HFrEF:** LVEF ≤40%; - **heart failure with mildly reduced EF:** LVEF 41–49% with evidence supporting heart failure; - **heart failure with preserved EF:** LVEF ≥50% with evidence supporting heart failure; - **heart failure with improved EF:** prior LVEF ≤40% followed by LVEF >40%. LVEF has measurement variability and changes with loading conditions, rhythm, revascularization, valve intervention, and treatment. Interpret the number alongside clinical trajectory and imaging quality. ## Etiology HFrEF is a syndrome. The cause should be actively defined because several etiologies require additional therapy. | Cause | Clues | Key next actions | |---|---|---| | Ischemic cardiomyopathy | Prior MI, angina, coronary risk, regional wall-motion abnormality | Define coronary anatomy/ischemia when revascularization could change management | | Dilated/genetic cardiomyopathy | Younger age, family cardiomyopathy or sudden death, conduction disease | Cardiac MRI; 3-generation family history; genetic counseling/testing when appropriate | | Hypertensive cardiomyopathy | Long-standing hypertension, LV hypertrophy | Optimize pressure and assess competing causes | | Valvular disease | Murmur, chamber remodeling, pulmonary hypertension | Full valve assessment; structural/surgical review when severe | | Myocarditis | Recent inflammatory illness, chest pain, arrhythmia | Cardiac MRI; myocarditis pathway when appropriate | | Tachycardia-mediated cardiomyopathy | Persistent AF/flutter/SVT or high ectopic burden | Quantify rhythm burden and pursue rate/rhythm control | | Alcohol or stimulant exposure | Heavy alcohol, cocaine, methamphetamine | Remove exposure and treat substance-use disorder | | Cancer therapy | Anthracycline, HER2-directed or other cardiotoxic exposure | Cardio-oncology review | | Endocrine/metabolic | Thyroid disease, iron overload, major nutritional deficiency | Cause-directed laboratory testing | | Infiltrative/inflammatory | Amyloid, sarcoidosis, hemochromatosis clues | Cardiac MRI and disease-specific testing | | Peripartum cardiomyopathy | Late pregnancy or postpartum onset | Cardio-obstetric care and pregnancy-compatible therapy | ## Pathophysiology Reduced systolic function lowers forward output and raises intracardiac filling pressures. Compensatory activation of the sympathetic nervous system, renin-angiotensin-aldosterone system, vasopressin, renal sodium retention, and vasoconstriction initially supports perfusion but subsequently promotes: - ventricular dilation and adverse remodeling; - myocardial fibrosis; - increased afterload; - sodium and water retention; - functional mitral regurgitation; - atrial and ventricular arrhythmia; - cardiorenal dysfunction; - sudden cardiac death. The core drug classes target different components of this biology, which is why combined therapy is more effective than sequential reliance on a single pathway.[1,2] ## Clinical assessment ### Symptoms - exertional dyspnea; - orthopnea or paroxysmal nocturnal dyspnea; - fatigue and reduced exercise tolerance; - peripheral edema; - abdominal distention or early satiety; - rapid weight gain from fluid retention; - nocturia; - presyncope or syncope; - cachexia in advanced disease. ### Bedside findings Document: - heart rate and rhythm; - blood pressure and orthostatic symptoms; - jugular venous pressure and hepatojugular reflux; - pulmonary crackles or pleural effusion; - third heart sound; - murmurs; - peripheral edema; - hepatomegaly or ascites; - cool extremities, delayed capillary refill, narrow pulse pressure; - frailty and muscle wasting. ### Congestion and perfusion | Profile | Perfusion | Congestion | Practical implication | |---|---|---|---| | Warm/dry | Adequate | Absent | Desired stable state | | Warm/wet | Adequate | Present | Most common decompensated profile; decongest | | Cold/wet | Reduced | Present | High risk; assess for shock and advanced HF | | Cold/dry | Reduced | Absent | Consider low output, overdiuresis, or advanced disease | ## Red flags and urgent escalation Hospital-level care is required for: - hypotension with altered mentation, oliguria, lactate elevation, cool/mottled skin, or other shock features; - severe respiratory distress or hypoxemia; - [acute coronary syndrome](/library/acute-coronary-syndrome); - sustained ventricular tachycardia or ventricular fibrillation; - high-grade bradyarrhythmia; - recurrent ICD shocks; - acute severe valve regurgitation or another mechanical complication; - syncope with suspected malignant arrhythmia; - rapidly worsening renal or hepatic dysfunction with congestion or low output. ## Diagnostic work-up ### Baseline studies Typical evaluation includes:[1] - 12-lead ECG; - CBC; - sodium, potassium, bicarbonate, urea/BUN, creatinine/eGFR; - glucose and HbA1c; - liver chemistry; - TSH; - ferritin and transferrin saturation; - urinalysis and urine albumin:creatinine ratio when kidney disease is relevant; - BNP or NT-proBNP; - chest radiography when pulmonary congestion or another thoracic process is possible; - transthoracic echocardiography. ### Natriuretic peptides BNP and NT-proBNP support diagnosis and prognosis. Concentrations can be higher with age, [atrial fibrillation](/library/atrial-fibrillation), and chronic kidney disease and lower than expected with obesity. After sacubitril/valsartan initiation, **NT-proBNP is easier to interpret serially** because neprilysin inhibition directly affects BNP metabolism. ### Echocardiography Define: - LVEF and LV dimensions; - RV size and function; - valve disease; - estimated pulmonary pressure; - regional wall-motion abnormalities; - pericardial disease; - filling-pressure and diastolic parameters. Repeat imaging after adequate treatment when recovery would change ICD/CRT or valve decisions, and whenever a meaningful clinical change suggests new structural disease. ### Cardiac MRI Use when tissue characterization or anatomy may clarify myocarditis, infiltrative disease, sarcoidosis, ischemic versus nonischemic scar, arrhythmic substrate, or uncertain echocardiographic EF. ### Ischemic assessment Evaluate for coronary disease when ischemia is plausible, the cause remains uncertain, or revascularization could alter prognosis or symptoms. Choose coronary CT angiography, stress imaging, or invasive angiography according to pretest probability, kidney function, symptoms, and revascularization intent. ## Initial management priorities 1. Determine whether the patient is stable or acutely decompensated. 2. Establish whether congestion is present and create a decongestion plan. 3. Start the four disease-modifying classes promptly when hemodynamically and biochemically safe. 4. Identify and treat the cause and reversible triggers. 5. Arrange early laboratory and clinical follow-up after each therapy change. 6. Reassess LVEF after adequate therapy if device candidacy is possible. ## Four core disease-modifying therapies ### Dosing and monitoring | Therapy | Typical starting dose | Target dose | Key monitoring | |---|---:|---:|---| | Sacubitril/valsartan | 24/26 or 49/51 mg twice daily | 97/103 mg twice daily | BP, potassium, creatinine/eGFR | | Carvedilol | 3.125 mg twice daily | 25 mg twice daily; 50 mg twice daily in selected larger patients | HR, BP, congestion | | Metoprolol succinate | 12.5–25 mg daily | 200 mg daily | HR, BP, congestion | | Bisoprolol | 1.25 mg daily | 10 mg daily | HR, BP, congestion | | Spironolactone | 12.5–25 mg daily | 25–50 mg daily | Potassium, creatinine/eGFR | | Eplerenone | 25 mg daily | 50 mg daily | Potassium, creatinine/eGFR | | Dapagliflozin | 10 mg daily | 10 mg daily | Volume status, renal trajectory, genital infection, ketoacidosis risk | | Empagliflozin | 10 mg daily | 10 mg daily | Volume status, renal trajectory, genital infection, ketoacidosis risk | Use jurisdiction-specific labeling for renal thresholds and dose restrictions.[1,2] ### ARNI and alternative renin-angiotensin therapy For symptomatic chronic HFrEF, ARNI is preferred when feasible. Sacubitril/valsartan reduced cardiovascular death and heart-failure hospitalization compared with enalapril in PARADIGM-HF.[1,6] If ARNI cannot be used, an ACE inhibitor or ARB remains appropriate when tolerated. Safety rules: - never combine ARNI with an ACE inhibitor; - allow **36 hours** after stopping an ACE inhibitor before starting sacubitril/valsartan; - avoid ARNI when prior angioedema creates a labeling contraindication; - monitor blood pressure, potassium, and kidney function. ### Evidence-based beta-blocker Use carvedilol, metoprolol succinate, or bisoprolol.[1] Start when the patient is clinically stable and not in cardiogenic shock. Chronic beta-blocker therapy is usually continued during decompensation unless shock, severe bradycardia, or another clear contraindication develops. New initiation or dose increase is best after stabilization and adequate decongestion. ### Mineralocorticoid receptor antagonist Use spironolactone or eplerenone when:[1] - **eGFR >30 mL/min/1.73 m²**, and - **potassium <5.0 mmol/L**. Check potassium and kidney function soon after initiation or dose increase and more frequently with CKD, diabetes, older age, or interacting drugs. If potassium cannot be maintained **<5.5 mmol/L**, discontinue the MRA.[1] ### SGLT2 inhibitor Dapagliflozin and empagliflozin reduce worsening-HF events in HFrEF with or without diabetes.[4,5] Practical points: - use **10 mg once daily** without titration; - expect a small early eGFR dip in some patients; - reassess loop-diuretic dose if volume depletion develops; - counsel about genital mycotic infection; - temporarily withhold during prolonged fasting, major surgery, or severe acute illness when ketoacidosis risk rises; - investigate nausea, abdominal pain, unexplained acidosis, or ketosis even when glucose is not markedly elevated. ## Sequencing and titration The 2024 ACC pathway recommends rapid establishment of all four core therapies and titration over roughly **3 months** when feasible.[2] | Clinical issue | Practical approach | |---|---| | Low-normal BP | Preserve SGLT2 inhibitor and MRA when possible; use lower ARNI/beta-blocker doses; remove nonessential vasodilators | | Tachycardia | Establish evidence-based beta-blocker once congestion and perfusion permit | | Hyperkalemia risk | Review potassium intake/drugs, optimize diuretic and SGLT2 strategy, intensify laboratory monitoring | | eGFR near MRA threshold | Use other core therapies within labeling; add MRA only when safety criteria are met | | Marked congestion | Decongest while maintaining or introducing disease-modifying therapy as stability permits | | Recent hospitalization | Fill GDMT gaps before discharge and arrange early post-discharge titration | > **Current practice:** Do not wait for a beta-blocker or ARNI to reach target before adding an SGLT2 inhibitor or MRA. Several therapies begin providing benefit early.[2,3] ## Diuretics and congestion Loop diuretics are used to achieve and maintain euvolemia. Common oral starting doses in diuretic-naive outpatients include: - furosemide **20–40 mg once or twice daily**; - torsemide **10–20 mg daily**; - bumetanide **0.5–1 mg once or twice daily**. Adjust according to prior exposure, kidney function, gut edema, response, and congestion. In acute decompensation, IV loop diuretics are usually required. Monitor: - dyspnea and orthopnea; - weight trajectory when useful; - JVP and edema; - urine output in acute care; - sodium, potassium, magnesium; - creatinine/eGFR. For inadequate loop response, reassess dose, absorption, adherence, perfusion, and renal function. Sequential nephron blockade with a thiazide-type diuretic can be used selectively with close electrolyte monitoring. The treatment target is **clinical decongestion**, not an unchanged creatinine value at the cost of persistent volume overload.[3] ## Additional therapy for selected patients ### Hydralazine plus isosorbide dinitrate A fixed-dose combination is recommended in self-identified Black patients with NYHA III–IV HFrEF receiving optimal therapy and may be considered when ARNI/ACE inhibitor/ARB cannot be used.[1] Typical fixed-dose treatment starts at **20 mg isosorbide dinitrate/37.5 mg hydralazine three times daily** and targets **40/75 mg three times daily** as tolerated.[1] ### Ivabradine Consider in selected stable symptomatic patients with: - LVEF ≤35%; - sinus rhythm; - resting heart rate ≥70/min; - maximally tolerated evidence-based beta-blocker.[1] Typical starting dose is **5 mg twice daily**, adjusted toward **7.5 mg twice daily** according to heart rate, age, and conduction status. ### Vericiguat May be considered in selected high-risk patients with recent worsening HFrEF despite optimized background therapy. A common titration is **2.5 mg daily → 5 mg daily → 10 mg daily** as tolerated.[1,2] ### Digoxin May reduce recurrent hospitalization in selected symptomatic HFrEF or assist rate control when alternatives are inadequate. Use conservatively in kidney dysfunction, older age, low body mass, hypokalemia, and interacting drug regimens. Typical maintenance is **0.125–0.25 mg daily**, often lower with CKD or frailty. When a chronic level is checked for HFrEF, a concentration around **0.5 to <0.9 ng/mL** is generally targeted.[1] ## Iron deficiency Check ferritin and transferrin saturation in symptomatic HFrEF. A commonly used definition is:[1] - ferritin **<100 ng/mL**; or - ferritin **100–300 ng/mL with transferrin saturation <20%**. IV iron is reasonable in selected symptomatic patients with documented iron deficiency to improve functional status and quality of life. Choice of preparation and repeat dosing follow local protocols and current labeling. Oral iron often performs poorly for functional iron deficiency in HFrEF. ## Atrial fibrillation and ventricular arrhythmia Atrial fibrillation can be a cause, consequence, or precipitant of HFrEF. Management includes: - anticoagulation according to thromboembolic risk; - rate control; - rhythm control when symptoms, tachycardia-mediated cardiomyopathy, or HF trajectory support it; - catheter ablation in appropriate patients; - correction of electrolyte, ischemic, and thyroid triggers. Sustained ventricular arrhythmia or recurrent ICD shocks requires urgent electrophysiology/cardiology review. ## Device therapy ### Implantable cardioverter-defibrillator Primary-prevention ICD is recommended for appropriate patients with:[1] - **LVEF ≤35%**; - NYHA II–III symptoms on chronic disease-modifying therapy; - expected meaningful survival >1 year. It is also recommended in selected post-MI patients with LVEF ≤30% and NYHA I symptoms after the appropriate post-infarction interval.[1] Avoid premature implantation before adequate recovery time after a new cardiomyopathy, revascularization, or major therapy optimization unless a secondary-prevention indication exists. ### Cardiac resynchronization therapy The strongest indication is:[1] - LVEF ≤35%; - sinus rhythm; - left bundle-branch block; - QRS ≥150 ms; - NYHA II–III or ambulatory IV symptoms despite therapy. Benefit is less consistent with non-left-bundle morphology or narrower QRS. CRT should not be used solely for QRS <120 ms.[1] ## Secondary mitral regurgitation Functional mitral regurgitation can improve with reverse remodeling. Before transcatheter or surgical valve intervention: 1. establish all tolerated core HFrEF therapies; 2. achieve euvolemia; 3. treat ischemia when indicated; 4. use CRT when criteria are met; 5. reassess regurgitation severity and anatomy. Persistent severe symptomatic secondary mitral regurgitation despite optimization warrants structural-heart review. ## Acute decompensated HFrEF ### Immediate priorities - identify precipitant and competing emergencies; - assess perfusion and shock; - give IV loop diuretic for clinically important congestion; - provide oxygen only when hypoxemic; - treat acute ischemia, infection, arrhythmia, hypertensive crisis, or other trigger; - avoid routine inotrope use unless low-output shock or another specific indication exists.[3] ### Disease-modifying therapy during hospitalization The 2024 ACC pathway emphasizes filling gaps in the four foundational therapies during hospitalization when the patient is stable enough.[3] A practical sequence is: 1. decongest and stabilize; 2. continue chronic disease-modifying therapy unless a real contraindication develops; 3. initiate SGLT2 inhibitor early when eligible; 4. add or optimize ARNI/ACE inhibitor/ARB, evidence-based beta-blocker, and MRA as hemodynamics and renal/potassium status permit; 5. define the outpatient titration plan before discharge. Patients with chronic class IV symptoms, marginal perfusion, or recent inotrope dependence may not tolerate standard titration and should receive advanced-HF input.[3] ### Discharge readiness Before discharge, confirm: - adequate decongestion or a clearly documented residual-volume strategy; - stable blood pressure and renal/electrolyte trajectory; - oral diuretic plan; - current and planned core therapies; - laboratory follow-up; - medication access and adherence barriers; - early post-discharge clinical review; - device/advanced-HF referral when indicated. ## Monitoring after therapy changes ### ARNI, ACE inhibitor, or ARB Track blood pressure, potassium, creatinine/eGFR, dizziness, and angioedema symptoms. ### MRA Check potassium and kidney function early after initiation or dose change and repeatedly during titration in high-risk patients. ### Beta-blocker Track resting heart rate, blood pressure, symptoms of bradycardia, and congestion. ### SGLT2 inhibitor Track volume status, renal trajectory, genital infection, and ketoacidosis risk during acute illness. ### Outpatient review Document: - NYHA functional status; - recent hospitalization or urgent IV diuretic use; - weight and congestion trajectory; - blood pressure and heart rate; - medication access and adherence; - kidney function and potassium; - iron status when indicated; - rhythm; - need for repeat echocardiography; - device eligibility; - goals of care in advanced disease. ## Heart failure with improved EF When a patient with prior LVEF ≤40% improves to >40%, continue HFrEF disease-modifying therapy unless a compelling contraindication exists.[1] TRED-HF demonstrated frequent relapse after withdrawal of therapy in recovered dilated cardiomyopathy.[8] Do not relabel recovery as cure without considering the underlying etiology and relapse risk. ## Advanced heart-failure referral Refer early when there is: - repeated HF hospitalization; - escalating loop-diuretic requirement; - persistent NYHA III–IV symptoms despite therapy; - hypotension preventing core therapy; - progressive renal or hepatic dysfunction; - recurrent ventricular arrhythmia or ICD shocks; - intolerance of several disease-modifying classes; - need for IV inotropes; - persistent low-output signs; - cardiac cachexia; - potential candidacy for transplant or durable mechanical circulatory support. Late referral can eliminate options when frailty, pulmonary vascular disease, kidney dysfunction, or liver dysfunction becomes irreversible. ## Special populations ### Chronic kidney disease and hyperkalemia CKD should not automatically lead to under-treatment. Use therapies within current renal thresholds, monitor closely, avoid NSAIDs, and distinguish a small expected hemodynamic eGFR change from progressive kidney injury. ### Low blood pressure Asymptomatic low blood pressure does not always require reducing all disease-modifying therapy. First review: - excess diuretic in a euvolemic patient; - nitrates or other nonessential vasodilators; - alpha-blockers or other pressure-lowering drugs without HFrEF outcome benefit; - dehydration. Preserve low doses across multiple outcome-improving classes when possible.[2] ### Pregnancy potential ACE inhibitors, ARBs, ARNIs, MRAs, and SGLT2 inhibitors are generally avoided during pregnancy. Peripartum cardiomyopathy requires coordinated cardio-obstetric management and pregnancy-compatible vasodilator, beta-blocker, and diuretic strategies. ### Older adults and frailty Use the same disease-modifying framework while accounting for orthostasis, kidney function, falls, cognition, polypharmacy, nutrition, and goals of care. Start lower when needed but do not treat age alone as a contraindication to beneficial therapy. ## Prognosis Prognosis depends on etiology, LVEF, symptoms, natriuretic peptide burden, kidney function, congestion, blood pressure, arrhythmia, frailty, recurrent worsening events, and response to therapy. A heart-failure hospitalization is a major prognostic event and should trigger a systematic review of: - all four core therapies; - dose and adherence; - congestion control; - rhythm; - ischemia; - valve disease; - device candidacy; - advanced-HF referral. ## Related library topics - [Acute Decompensated Heart Failure](acute-decompensated-heart-failure.md) - [Heart Failure With Preserved Ejection Fraction](heart-failure-with-preserved-ejection-fraction.md) - [Atrial Fibrillation](atrial-fibrillation.md) - [Acute Coronary Syndrome](acute-coronary-syndrome.md) - [Mitral Regurgitation in Adults](mitral-regurgitation-in-adults.md) - [Chronic Kidney Disease](../nephrology/chronic-kidney-disease.md) - [Hyperkalemia](../nephrology/hyperkalemia.md) ## References 1. Heidenreich PA, Bozkurt B, Aguilar D, et al. **2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.** *Circulation.* 2022;145:e895-e1032. doi:10.1161/CIR.0000000000001063. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001063 2. Maddox TM, Januzzi JL Jr, Allen LA, et al. **2024 ACC Expert Consensus Decision Pathway for Treatment of Heart Failure With Reduced Ejection Fraction.** *J Am Coll Cardiol.* 2024;83(15):1444-1488. doi:10.1016/j.jacc.2023.12.024. PMID:38466244. https://doi.org/10.1016/j.jacc.2023.12.024 3. Hollenberg SM, Stevenson LW, Ahmad T, et al. **2024 ACC Expert Consensus Decision Pathway on Clinical Assessment, Management, and Trajectory of Patients Hospitalized With Heart Failure Focused Update.** *J Am Coll Cardiol.* 2024;84(13):1241-1267. doi:10.1016/j.jacc.2024.06.002. PMID:39127954. https://doi.org/10.1016/j.jacc.2024.06.002 4. McMurray JJV, Solomon SD, Inzucchi SE, et al. **Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction.** *N Engl J Med.* 2019;381:1995-2008. doi:10.1056/NEJMoa1911303. PMID:31535829. https://doi.org/10.1056/NEJMoa1911303 5. Packer M, Anker SD, Butler J, et al. **Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure.** *N Engl J Med.* 2020;383:1413-1424. doi:10.1056/NEJMoa2022190. PMID:32865377. https://doi.org/10.1056/NEJMoa2022190 6. McMurray JJV, Packer M, Desai AS, et al. **Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure.** *N Engl J Med.* 2014;371:993-1004. doi:10.1056/NEJMoa1409077. PMID:25176015. https://doi.org/10.1056/NEJMoa1409077 7. Pitt B, Zannad F, Remme WJ, et al. **The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure.** *N Engl J Med.* 1999;341:709-717. doi:10.1056/NEJM199909023411001. PMID:10471456. https://doi.org/10.1056/NEJM199909023411001 8. Halliday BP, Wassall R, Lota AS, et al. **Withdrawal of Pharmacological Treatment for Heart Failure in Patients with Recovered Dilated Cardiomyopathy (TRED-HF).** *Lancet.* 2019;393:61-73. doi:10.1016/S0140-6736(18)32484-X. PMID:30429050. https://pubmed.ncbi.nlm.nih.gov/30429050/7:["$","$L17",null,{"article":{"id":"medical-heart-failure-with-reduced-ejection-fraction","title":"Heart Failure With Reduced Ejection Fraction (HFrEF)","slug":"heart-failure-with-reduced-ejection-fraction","description":"Heart failure with reduced ejection fraction (HFrEF) is a clinical heart-failure syndrome with left ventricular ejection fraction (LVEF) ≤40% in the current U.S. framework. A low LVEF alone is not sufficient: confirm…","aliases":[],"category":"Cardiology","tags":["Cardiology"],"updatedAt":"$undefined","body":"$18","headings":[{"id":"summary","text":"Summary","level":2},{"id":"definition-and-phenotype","text":"Definition and phenotype","level":2},{"id":"etiology","text":"Etiology","level":2},{"id":"pathophysiology","text":"Pathophysiology","level":2},{"id":"clinical-assessment","text":"Clinical assessment","level":2},{"id":"symptoms","text":"Symptoms","level":3},{"id":"bedside-findings","text":"Bedside findings","level":3},{"id":"congestion-and-perfusion","text":"Congestion and perfusion","level":3},{"id":"red-flags-and-urgent-escalation","text":"Red flags and urgent escalation","level":2},{"id":"diagnostic-work-up","text":"Diagnostic work-up","level":2},{"id":"baseline-studies","text":"Baseline studies","level":3},{"id":"natriuretic-peptides","text":"Natriuretic peptides","level":3},{"id":"echocardiography","text":"Echocardiography","level":3},{"id":"cardiac-mri","text":"Cardiac MRI","level":3},{"id":"ischemic-assessment","text":"Ischemic assessment","level":3},{"id":"initial-management-priorities","text":"Initial management priorities","level":2},{"id":"four-core-disease-modifying-therapies","text":"Four core disease-modifying therapies","level":2},{"id":"dosing-and-monitoring","text":"Dosing and monitoring","level":3},{"id":"arni-and-alternative-renin-angiotensin-therapy","text":"ARNI and alternative renin-angiotensin therapy","level":3},{"id":"evidence-based-beta-blocker","text":"Evidence-based beta-blocker","level":3},{"id":"mineralocorticoid-receptor-antagonist","text":"Mineralocorticoid receptor antagonist","level":3},{"id":"sglt2-inhibitor","text":"SGLT2 inhibitor","level":3},{"id":"sequencing-and-titration","text":"Sequencing and titration","level":2},{"id":"diuretics-and-congestion","text":"Diuretics and congestion","level":2},{"id":"additional-therapy-for-selected-patients","text":"Additional therapy for selected patients","level":2},{"id":"hydralazine-plus-isosorbide-dinitrate","text":"Hydralazine plus isosorbide dinitrate","level":3},{"id":"ivabradine","text":"Ivabradine","level":3},{"id":"vericiguat","text":"Vericiguat","level":3},{"id":"digoxin","text":"Digoxin","level":3},{"id":"iron-deficiency","text":"Iron deficiency","level":2},{"id":"atrial-fibrillation-and-ventricular-arrhythmia","text":"Atrial fibrillation and ventricular arrhythmia","level":2},{"id":"device-therapy","text":"Device therapy","level":2},{"id":"implantable-cardioverter-defibrillator","text":"Implantable cardioverter-defibrillator","level":3},{"id":"cardiac-resynchronization-therapy","text":"Cardiac resynchronization therapy","level":3},{"id":"secondary-mitral-regurgitation","text":"Secondary mitral regurgitation","level":2},{"id":"acute-decompensated-hfref","text":"Acute decompensated HFrEF","level":2},{"id":"immediate-priorities","text":"Immediate priorities","level":3},{"id":"disease-modifying-therapy-during-hospitalization","text":"Disease-modifying therapy during hospitalization","level":3},{"id":"discharge-readiness","text":"Discharge readiness","level":3},{"id":"monitoring-after-therapy-changes","text":"Monitoring after therapy changes","level":2},{"id":"arni-ace-inhibitor-or-arb","text":"ARNI, ACE inhibitor, or ARB","level":3},{"id":"mra","text":"MRA","level":3},{"id":"beta-blocker","text":"Beta-blocker","level":3},{"id":"sglt2-inhibitor","text":"SGLT2 inhibitor","level":3},{"id":"outpatient-review","text":"Outpatient review","level":3},{"id":"heart-failure-with-improved-ef","text":"Heart failure with improved EF","level":2},{"id":"advanced-heart-failure-referral","text":"Advanced heart-failure referral","level":2},{"id":"special-populations","text":"Special populations","level":2},{"id":"chronic-kidney-disease-and-hyperkalemia","text":"Chronic kidney disease and hyperkalemia","level":3},{"id":"low-blood-pressure","text":"Low blood pressure","level":3},{"id":"pregnancy-potential","text":"Pregnancy potential","level":3},{"id":"older-adults-and-frailty","text":"Older adults and frailty","level":3},{"id":"prognosis","text":"Prognosis","level":2},{"id":"related-library-topics","text":"Related library topics","level":2},{"id":"references","text":"References","level":2}],"readingMinutes":16},"linkedMarkdown":"$19","backlinks":[],"related":[],"previewBySlug":{"abcde-approach":{"title":"ABCDE Approach","description":"The ABCDE approach is a structured method for the immediate assessment and treatment of a deteriorating or critically ill patient: Airway, Breathing, Circulation, Disability, Exposure. The central rule is treat life-t…","category":"Emergency Medicine"},"acute-asthma-exacerbation":{"title":"Acute Asthma Exacerbation","description":"An asthma exacerbation is an acute or subacute worsening of dyspnea, wheeze, cough or chest tightness with a fall in expiratory airflow compared with the patient’s usual state. The attack is caused by variable airflow…","category":"Pulmonology"},"bacterial-meningitis":{"title":"Acute Bacterial Meningitis","description":"Acute bacterial meningitis is infection-driven inflammation of the leptomeninges and cerebrospinal fluid (CSF). It can progress over hours to sepsis, shock, cerebral edema, seizures, raised intracranial pressure, hern…","category":"Infectious Disease"},"acute-coronary-syndrome":{"title":"Acute Coronary Syndrome","description":"Acute coronary syndrome (ACS) is the clinical spectrum caused most often by acute coronary atherothrombosis after plaque rupture or erosion and includes ST-elevation myocardial infarction (STEMI), non-ST-elevation myo…","category":"Cardiology"},"acute-ischemic-stroke":{"title":"Acute Ischemic Stroke","description":"Acute ischemic stroke (AIS) is sudden neurological dysfunction caused by focal cerebral, retinal, or spinal cord ischemia, most often from arterial occlusion. The practical emergency question is not simply “is this a…","category":"Neurology"},"acute-kidney-injury":{"title":"Acute Kidney Injury","description":"Acute kidney injury (AKI) is an abrupt decline in kidney function identified by a rise in serum creatinine and/or reduced urine output. The current established international definition remains the KDIGO 2012 definitio…","category":"Nephrology"},"acute-pulmonary-embolism":{"title":"Acute Pulmonary Embolism","description":"Acute pulmonary embolism (PE) is obstruction of the pulmonary arterial circulation by thrombus, usually arising from deep veins of the legs or pelvis. The immediate threat is acute right-ventricular (RV) pressure over…","category":"Pulmonology"},"atrial-fibrillation":{"title":"Atrial Fibrillation","description":"Atrial fibrillation (AF) is a supraventricular tachyarrhythmia characterized by chaotic atrial electrical activation and ineffective atrial contraction. On ECG it produces irregularly irregular RR intervals (when AV c…","category":"Cardiology"},"diabetic-ketoacidosis":{"title":"Diabetic Ketoacidosis","description":"Diabetic ketoacidosis (DKA) is an acute metabolic emergency caused by insufficient effective insulin activity together with excess counterregulatory hormones, producing ketogenesis, metabolic acidosis, osmotic diuresi…","category":"Endocrinology"},"dyslipidemia-in-adults":{"title":"Dyslipidemia in Adults","description":"Dyslipidemia is an abnormal concentration or composition of circulating lipoproteins that increases atherosclerotic cardiovascular disease (ASCVD) risk or, when triglycerides are very high, pancreatitis risk. LDL-cont…","category":"Cardiology"},"sepsis-and-septic-shock":{"title":"Sepsis and Septic Shock","description":"Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Operationally, Sepsis-3 identifies organ dysfunction as an acute increase in SOFA score ≥2 points attributable to infec…","category":"Critical Care"},"upper-gastrointestinal-bleeding":{"title":"Upper Gastrointestinal Bleeding","description":"Upper gastrointestinal bleeding (UGIB) is bleeding arising proximal to the ligament of Treitz. It most commonly presents with hematemesis, coffee-ground emesis, melena, or—when brisk—hematochezia with hemodynamic inst…","category":"Gastroenterology"}},"categories":["Cardiology","Critical Care","Emergency Medicine","Endocrinology","Gastroenterology","Infectious Disease","Nephrology","Neurology","Pulmonology"]}]