# Heart Failure

Heart failure requires phenotype-specific confirmation, rapid identification of reversible precipitants, early disease-modifying therapy for reduced ejection fraction, and surveillance for congestion, arrhythmia, renal dysfunction, and progression to advanced therapies. Management must align treatment intensity with hemodynamics, comorbidity, and patient goals.

**Clinical question:** How should clinicians confirm, phenotype, treat, and longitudinally monitor heart failure while identifying candidates for advanced therapies?

Updated: 2026-08-20T23:32:30.158442Z

## What matters in practice
- Heart failure is a clinical syndrome; reduced ejection fraction alone does not establish the diagnosis without compatible symptoms or signs. [10]
- Determine ejection-fraction phenotype, structural cause, congestion, perfusion, rhythm, ischemic substrate, valvular disease, and reversible precipitants before assigning long-term therapy. [10][11]
- For HFrEF, guideline-directed therapy includes an ARNI, evidence-based beta blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor, with individualized sequencing and monitoring. [11]
- Loop diuretics relieve congestion but do not substitute for disease-modifying therapy; in obstructive hypertrophic cardiomyopathy, excessive preload reduction can worsen outflow obstruction. [8]
- Advanced heart failure can occur with preserved EF in restrictive hypertrophic cardiomyopathy; transplant referral should not be deferred solely because EF is preserved. [8]

## Confirm the syndrome and define the phenotype

Use symptoms, examination, biomarkers, imaging, and etiologic assessment rather than ejection fraction alone.

Heart failure is a clinical syndrome caused by structural or functional impairment of ventricular filling or ejection. Dyspnea, fatigue, congestion, and edema are common but nonspecific; no single diagnostic test is sufficient. A prior low EF without clinical evidence of heart failure should not be equated with heart failure. [10][23]

Initial assessment should establish acuity, congestion versus hypoperfusion, blood pressure, rhythm, ischemic symptoms, valve disease, renal and hepatic dysfunction, and competing cardiopulmonary diagnoses. Obtain ECG, chest radiography when clinically useful, CBC, renal function and electrolytes, liver tests, thyroid testing, glycemic assessment, and transthoracic echocardiography to evaluate ventricular systolic and diastolic function, valves, chamber size, and shunts. [23]

Classify by LVEF: HFrEF at 40% or less, HFmrEF above 40% to below 50%, HFpEF at 50% or greater, and HF with recovered EF when a previously reduced EF improves to at least 50%. These categories guide evidence application but do not define etiology or filling pressures. [10]
- Use natriuretic peptides to support or weaken diagnostic probability, recognizing that age, renal dysfunction, tachycardia, right-sided pressure overload, hypoxemia, sepsis, COPD, diabetes, and cirrhosis can elevate values; obesity and treatment with diuretics, ACE inhibitors, ARBs, beta blockers, or mineralocorticoid receptor antagonists can lower them. [23]
- If echocardiography is nondiagnostic or image quality is inadequate, cardiac MRI can clarify ventricular structure, function, scar, inflammation, or infiltrative disease; CT is an alternative when echo is limited and CMR is unavailable or contraindicated. [8]

*Core diagnostic framework for suspected heart failure. [10][23]*

| Clinical question | Action | Interpretation or next step |
| --- | --- | --- |
| Is the syndrome present? | Integrate symptoms, signs, examination, and objective testing. | Do not diagnose heart failure from LVEF alone. [10] |
| Is cardiac dysfunction or structural disease present? | Perform transthoracic echocardiography. | Assess LVEF, diastolic function, valves, chamber dimensions, and shunts. [23] |
| Is natriuretic peptide testing useful? | Measure NT-proBNP when heart failure is suspected. | In untreated patients, NT-proBNP below 400 ng/L makes heart failure less likely in the NICE pathway; values above 2,000 ng/L warrant urgent specialist assessment and echocardiography within 2 weeks. This is a UK pathway, not a U.S. threshold recommendation. [23] |
| Is etiology actionable? | Assess ischemia, hypertension, valvular disease, arrhythmia, cardiomyopathy, toxin exposure, infiltrative disease, congenital disease, and systemic causes. | Treatable cause identification changes therapy, prognosis, and referral. [10][11] |

## Build phenotype-directed long-term therapy

Separate symptom relief from therapies that alter morbidity and mortality.

The supplied U.S. heart failure guideline is the principal source for patient-centered prevention, diagnosis, and management recommendations, but detailed drug dose tables are not available in the provided search excerpts. Therefore, this review names core medication classes without adding unsupported dose or titration schedules. [11]

In HFrEF, foundational therapy includes renin-angiotensin system modulation with an ARNI or other appropriate RAAS-directed therapy, an evidence-based beta blocker, a mineralocorticoid receptor antagonist, and an SGLT2 inhibitor. The 2022 AHA/ACC/HFSA guideline is the key U.S. reference for selection, sequencing, eligibility, and monitoring. [11]

Sacubitril/valsartan is FDA-indicated to reduce cardiovascular death and heart failure hospitalization in adults with chronic heart failure, with benefit most clearly evident when LVEF is below normal. The usual adult starting dose is 49/51 mg orally twice daily, titrated every 2 to 4 weeks as tolerated to 97/103 mg twice daily; begin at half the usual starting dose for severe renal impairment, moderate hepatic impairment, or no/low prior ACE inhibitor or ARB exposure. Do not coadminister with an ACE inhibitor; allow a 36-hour washout when switching from an ACE inhibitor. [2]

Metoprolol succinate is FDA-indicated for stable symptomatic NYHA II or III heart failure. Start 25 mg once daily for 2 weeks in NYHA II or 12.5 mg once daily in more severe heart failure, then double every 2 weeks to the highest tolerated dose or 200 mg daily. Stabilize other heart failure therapy first; with transient worsening heart failure, intensify diuresis and restore clinical stability before further titration. Avoid abrupt discontinuation. [3]
- Monitor blood pressure, renal function, potassium, heart rate, volume status, and symptom trajectory during initiation and titration of disease-modifying therapy. Sacubitril/valsartan can cause hypotension, hyperkalemia, renal dysfunction, and angioedema. [2]
- Use loop diuretics for congestion. Thiazide-like diuretics such as chlorthalidone can cause hypokalemia, hyponatremia, hypomagnesemia, hyperuricemia, hyperglycemia, and acute kidney injury from hypovolemia; monitor renal function and electrolytes. [7]
- Dapagliflozin labeling includes warnings for ketoacidosis and volume depletion; review full prescribing information when selecting an SGLT2 inhibitor, especially in patients with diabetes, reduced intake, acute illness, or diuretic-associated volume depletion. [6]

### Acute congestion and decompensation

Acute pulmonary edema or pulmonary congestion requires rapid assessment of oxygenation, perfusion, blood pressure, ischemia, arrhythmia, renal function, and precipitating causes. Invasive hemodynamics may be useful when noninvasive testing does not resolve diagnostic uncertainty or when refractory symptoms require precise characterization of filling pressures, cardiac output, and pulmonary pressures. [10][11]
- Avoid routine initiation of high-dose extended-release metoprolol immediately before noncardiac surgery; perioperative initiation in a trial was associated with more bradycardia, hypotension, stroke, and death. Chronic beta-blocker therapy should not routinely be withdrawn before major surgery. [3]
- For patients treated with sacubitril/valsartan who develop hypotension, address volume depletion and reconsider concomitant diuretics or antihypertensives before permanent discontinuation when feasible. [2]

*Selected FDA-supported medication details relevant to chronic heart failure. [2][3]*

| Agent | Use and dosing | Key safety actions |
| --- | --- | --- |
| Sacubitril/valsartan | Chronic heart failure: start 49/51 mg twice daily; double after 2-4 weeks as tolerated to 97/103 mg twice daily. Use half the usual starting dose with severe renal impairment, moderate hepatic impairment, or no/low prior ACE inhibitor or ARB exposure. [2] | Contraindicated with ACE inhibitors and in prior ACE inhibitor- or ARB-related angioedema; require 36-hour ACE inhibitor washout. Monitor potassium and renal function. [2] |
| Metoprolol succinate | Stable symptomatic NYHA II-III heart failure: 25 mg once daily for NYHA II or 12.5 mg once daily for more severe heart failure; double every 2 weeks to highest tolerated dose or 200 mg daily. [3] | Do not initiate in decompensated heart failure. Monitor for bradycardia and worsening congestion during titration; taper over 1-2 weeks if discontinuing chronic therapy. [3] |

## Modify treatment when cardiomyopathy physiology changes the risk

Heart failure management changes substantially when obstruction, infiltrative disease, or systolic decline is present.

In obstructive hypertrophic cardiomyopathy, dynamic outflow obstruction is sensitive to preload, afterload, and contractility. A peak LVOT gradient of at least 30 mm Hg defines obstruction; resting or provoked gradients of at least 50 mm Hg are generally considered capable of causing symptoms and are the threshold for advanced pharmacologic or invasive strategies when symptoms are refractory. [8]

For symptomatic obstructive hypertrophic cardiomyopathy, nonvasodilating beta blockers are first-line. Verapamil or diltiazem are alternatives. Persistent symptoms despite first-line therapy may prompt consideration of a cardiac myosin inhibitor in adults, disopyramide with an AV nodal blocking agent, or septal reduction therapy at an experienced HCM center. [8]

Avoid or reconsider pure vasodilators, high-dose diuretics, and positive inotropes in symptomatic obstructive hypertrophic cardiomyopathy because reduced preload or afterload and increased contractility can worsen obstruction. Low-dose diuretics may be used cautiously for persistent congestive symptoms. [8]
- Mavacamten reduces contractility and can reduce LVEF. In HCM, interrupt cardiac myosin inhibitor therapy if LVEF falls below 50%; restart at a lower dose only if LVEF recovers. [8]
- For HCM with persistent systolic dysfunction defined by LVEF below 50%, evaluate alternative contributors including coronary disease, valvular disease, metabolic disease, and phenocopies, and apply HFrEF guideline-directed therapy as tolerated. [8]
- Consider referral to a comprehensive HCM center for complex diagnosis, genetic counseling, ICD decisions, septal reduction therapy, advanced heart failure therapies, or management of refractory arrhythmias. [8]

*Management implications of obstructive hypertrophic cardiomyopathy with heart failure symptoms. [8]*

| Finding | Clinical implication | Action |
| --- | --- | --- |
| Resting or provoked LVOT gradient ≥50 mm Hg with attributable symptoms | Hemodynamically important obstruction is likely. | Use nonvasodilating beta blocker first; escalate to disopyramide, adult myosin inhibitor, or septal reduction therapy if refractory. [8] |
| Congestion with obstructive physiology | Diuresis may relieve symptoms but can worsen obstruction by reducing preload. | Use low-dose diuretics cautiously and reassess symptoms, blood pressure, and gradient. [8] |
| LVEF <50% during myosin inhibitor therapy | Potential drug-related systolic dysfunction. | Interrupt therapy; consider lower-dose restart only after recovery. [8] |

## Monitor trajectory and refer before advanced disease becomes irreversible

Serial assessment should detect congestion, arrhythmia, progressive dysfunction, and advanced-therapy eligibility.

Follow-up should include symptoms, NYHA class, blood pressure, heart rate and rhythm, weight and volume status, renal function, electrolytes, medication tolerance, and adherence. Heart failure data standards also identify functional assessment, patient-reported outcomes, cardiopulmonary exercise testing, rhythm monitoring, and invasive hemodynamics as appropriate tools in selected patients. [10]

In hypertrophic cardiomyopathy, serial transthoracic echocardiography every 1 to 2 years in asymptomatic patients can assess changes in systolic and diastolic function, wall thickness, chamber size, LVOT obstruction, and valvular disease. Ambulatory ECG monitoring every 1 to 2 years is reasonable for arrhythmia surveillance in patients without ICDs. [8]

Advanced heart failure develops in an estimated 3% to 8% of patients with hypertrophic cardiomyopathy. Refer for transplant evaluation when severe symptoms or recurrent ventricular arrhythmias persist despite optimized medical therapy and septal reduction is not an option; preserved EF does not exclude advanced restrictive physiology or transplant candidacy. [8]
- Use cardiopulmonary exercise testing when evaluating severe symptoms or transplant candidacy; reduced peak oxygen consumption, impaired ventilatory efficiency, and abnormal anaerobic threshold are associated with adverse outcomes in HCM. [8]
- For atrial fibrillation in HCM, oral anticoagulation is generally the default irrespective of CHA2DS2-VASc score because thromboembolic risk is elevated; direct oral anticoagulants are supported as at least as effective as warfarin in observational data. [8]
- Reassess sudden cardiac death risk in HCM every 1 to 2 years. Risk assessment incorporates prior cardiac arrest or sustained ventricular arrhythmia, family history, unexplained syncope, ventricular wall thickness, apical aneurysm, LVEF, ambulatory NSVT, and CMR fibrosis. [8]

*High-value longitudinal surveillance in heart failure and HCM. [8][10]*

| Domain | What to measure | Escalation trigger |
| --- | --- | --- |
| Congestion and treatment tolerance | Weight, symptoms, blood pressure, renal function, potassium, and diuretic response. | Progressive congestion, hypotension, hyperkalemia, or clinically significant renal decline requires medication and volume reassessment. [2][7] |
| HCM anatomy and hemodynamics | TTE with resting and provoked LVOT gradient when relevant. | New symptoms, provoked gradient ≥50 mm Hg, progressive mitral regurgitation, or systolic decline should prompt treatment reassessment. [8] |
| Advanced heart failure | NYHA class, recurrent hospitalizations, refractory symptoms, ventricular arrhythmias, and CPET. | Refer for advanced heart failure or transplant evaluation when optimized therapy and anatomy-directed options are exhausted. [8] |

## Common questions

### What establishes a diagnosis of heart failure?

Diagnosis requires compatible clinical symptoms or signs plus evidence of relevant structural or functional cardiac abnormality; a reduced LVEF alone is insufficient. [10][23]

### How should suspected heart failure be evaluated initially?

Use history, examination, ECG, laboratories for reversible contributors, natriuretic peptide testing when appropriate, and transthoracic echocardiography to define function, structure, valves, and shunts. [23]

### When should sacubitril/valsartan not be used?

Do not use with an ACE inhibitor or within 36 hours of ACE inhibitor exposure, in patients with prior ACE inhibitor- or ARB-related angioedema, or with aliskiren in diabetes. Monitor renal function and potassium. [2]

### When should patients with hypertrophic cardiomyopathy be referred to an expert center?

Refer for complex diagnostic or genetic issues, difficult ICD decisions, refractory obstruction, septal reduction therapy, complex arrhythmia management, or advanced heart failure and transplant assessment. [8]

### Can advanced heart failure occur with preserved ejection fraction?

Yes. In hypertrophic cardiomyopathy, restrictive physiology can produce severe heart failure despite preserved EF; advanced therapy and transplant referral should be based on clinical trajectory, not EF alone. [8]

## References
1. prescribing information - accessdata.fda.gov — www.accessdata.fda.gov — https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020702Orig1s079correctedlbl.pdf
2. ENTRESTO® (sacubitril and valsartan) tablets, for oral use ... — www.accessdata.fda.gov — https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/207620s025,218591s000lbl.pdf
3. Metoprolol succinate - accessdata.fda.gov — www.accessdata.fda.gov — https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019962s041lbl.pdf
4. FDA Approves First Generic Pimobendan for Management of Congestive Heart Failure in Dogs | FDA — www.fda.gov — https://www.fda.gov/animal-veterinary/cvm-updates/fda-approves-first-generic-pimobendan-management-congestive-heart-failure-dogs
5. These highlights do not include all the information needed to use VALSARTAN TABLETS safely and effectively. See full prescribing information for VALSARTAN TABLETS.
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VALSARTAN tablets, for oral use
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Initial U.S. Approval: 1996 — www.accessdata.fda.gov — https://www.accessdata.fda.gov/spl/data/f755ffef-66fc-1de5-e053-6294a90ab746/f755ffef-66fc-1de5-e053-6294a90ab746.xml
6. FDA Approves First Generic Dapagliflozin Tablets | FDA — www.fda.gov — https://www.fda.gov/drugs/drug-alerts-and-statements/fda-approves-first-generic-dapagliflozin-tablets
7. These highlights do not include all the information needed to use HEMICLOR<sup>TM </sup>safely and effectively. See full prescribing information for HEMICLOR.<br/> <br/>HEMICLOR (chlorthalidone) tablets, for oral use<br/>Initial U.S. Approval: 1960 — nctr-crs.fda.gov — https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/3f0f3ee0-f5a6-4bda-8160-a77744e9fa46/spl-doc?hl=
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14. Hydralazine Plus Isosorbide Dinitrate - an overview — www.sciencedirect.com — https://www.sciencedirect.com/topics/nursing-and-health-professions/hydralazine-plus-isosorbide-dinitrate
15. Prognostic impact of the coexistence of hepato-renal ... — www.sciencedirect.com — https://www.sciencedirect.com/science/article/pii/S0914508722002234
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United States, 1980-1995 — www.cdc.gov — https://www.cdc.gov/mmwr/preview/mmwrhtml/00054249.htm
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## Editorial note

Prepared from cited clinical literature using Astra's research workflow. Verify recommendations against current guidance and patient-specific factors.