Heart Failure

Contents. #Details · #Key Facts · #Classification · #Pathophysiology · #Diagnosis · #Decompensated heart failure · #Advanced heart failure · #Special populations · #Contradictions / Open Questions · #Sources

Detailed pages. entities/HFrEF — the reduced-EF phenotype: definition, pathophysiology, diagnosis, HFimpEF. entities/HFpEF — the preserved-EF phenotype: diagnostic scores, the ASE algorithm, latent HFpEF.

Management pages. concepts/HFrEF-Management — four pillars, additional agents, revascularisation, ICD/CRT/TEER. concepts/HFpEF-Management — outcome trials, SGLT2i and MRA, obesity-HFpEF, iron. Decompensation: concepts/Decompensated-HF-Management.

Details

Heart failure is a clinical syndrome of symptoms (dyspnoea, ankle swelling, fatigue) and/or signs (elevated JVP, pulmonary crackles, peripheral oedema) caused by a cardiac structural or functional abnormality that raises intracardiac pressures or limits cardiac output at rest or on effort. The 2026 ESC guideline abolished HFmrEF and divided HF into two phenotypes only — HFrEF at LVEF <50% and HFpEF at LVEF ≥50% — on the argument that LVEF 41–49% behaves like HFrEF in aetiology, pathophysiology and treatment response. Stages A–D, previously an ACC/AHA construct, are now adopted by both guidelines, which is what gives the classification a lever for intervening before symptoms appear. (sources/HF-ESC-2026, rating: very high; sources/HF-AHA-2022)

The distinction that matters clinically is what follows from it. SGLT2 inhibitors and MRAs are now Class I, Level A in all symptomatic HF regardless of ejection fraction, so both phenotypes share two foundational drugs; what separates them is everything else — HFrEF adds a beta-blocker and a renin-axis inhibitor, HFpEF adds nothing but comorbidity control, and only HFrEF has device therapy with randomised mortality evidence. (sources/HF-ESC-2026)

Key Facts

• Prevalence 1–2% of adults in developed countries, rising above 10% over age 70; 1-year mortality around 20% and 5-year mortality 53–67%. (sources/HF-ESC-2021, rating: very high)
• Outpatient phenotype distribution is 60% HFrEF, 24% HFmrEF and 16% HFpEF — but HFpEF predominates in hospital and community cohorts, where it is under-represented by registry sampling. (sources/HF-ESC-2021)
• Foundational medical therapy in HFrEF — SGLT2i, MRA, beta-blocker and ACE-I/ARNI/ARB — reduces estimated all-cause mortality by about 73% versus no treatment. (sources/HF-AHA-2022)
• SGLT2 inhibitors and MRAs are both Class I, Level A across the whole EF spectrum in the 2026 ESC guideline. MRA in HFpEF is the newer of the two and rests on a pooled analysis of TOPCAT and FINEARTS-HF rather than a positive trial of spironolactone. (sources/HF-ESC-2026, rating: very high)
• No pharmacotherapy has reduced mortality in HFpEF. SGLT2i, finerenone, semaglutide and tirzepatide all reduced hospitalisation or symptoms, not death — and the 2026 ESC Task Force says explicitly that it graded on the primary composite for this reason. (sources/HF-ESC-2026, sources/finerenone-hfpef-fineartshf-nejm-2024)
• Hospitalisation averages once per year, and 63% of admissions are for non-cardiovascular causes — a reminder that competing comorbidity, not pump failure, drives much of the burden. AF, BMI, HbA1c and eGFR are the key hospitalisation predictors. (sources/HF-ESC-2021)
• HF is the leading indication for cardiac transplantation in adults, and advanced HF is defined by therapeutic refractoriness rather than by EF alone. (sources/HF-ESC-2021, sources/HF-AHA-2022)

Classification

LVEF phenotypes — ESC 2026 versus ACC/AHA 2022

The two guidelines no longer share a classification. ESC abolished HFmrEF in 2026 and raised the HFrEF ceiling to 50%; AHA/ACC/HFSA kept four categories in 2022 and is still the reference used in the United States.

(Table: sources/HF-ESC-2026, rating: very high; sources/HF-AHA-2022)

Therapy maps onto the same split. If 41–49% is HFrEF, the band inherits the full four foundational drugs at Class I; if it is HFmrEF, it gets an SGLT2i at COR 2a and everything else at COR 2b. Identical trial data, materially different treatment intensity. Mechanisms: entities/HFrEF and entities/HFpEF. Pathways: concepts/HFrEF-Management and concepts/HFpEF-Management.

Why HFmrEF was abolished — and why it survives in the US

HFmrEF existed from 2016 to 2026 and was never backed by a dedicated trial: the 41–49% band was always analysed as a subgroup, and both pivotal SGLT2i trials enrolled LVEF >40% rather than 41–49% specifically. The 2026 Task Force retired it because its aetiology, pathophysiology (reduced contractility rather than increased stiffness) and treatment response all resemble HFrEF. Two things follow: the European recommendation is stronger than its evidence, and the American guideline still treats the band as a distinct entity requiring documented raised filling pressures. The disagreement is really about whether 41–49% is a phenotype or a transition state. (sources/HF-ESC-2026, rating: very high; sources/HF-AHA-2022)

Staging A–D

The A–D stages are orthogonal to the LVEF phenotypes — a patient has both. Adopting them was one of the few classification changes the ESC made in the AHA's direction.

(Table: sources/HF-ESC-2026, rating: very high; sources/HF-AHA-2022)

Stage B is where the two guidelines earn their keep: the ESC 2026 beta-blocker recommendation now extends to LVEF <50%, not the older ≤40%, on the strength of an individual-patient meta-analysis showing similar mortality reduction at LVEF 40–50%.

HFimpEF

• Definition: an absolute LVEF rise of ≥10% to above 40% after treatment. Deliberately framed as remission rather than recovery — structural abnormalities, biomarker abnormalities and relapse risk persist. (sources/HF-ESC-2026, rating: very high; sources/HF-AHA-2022)
• Continue treatment even when asymptomatic (ESC Class I/C; AHA COR 1): withdrawal in TRED-HF produced relapse in 40% within six months. A single-centre open-label pilot, CATHEDRAL-HF, did not reproduce that relapse rate — the only counter-evidence, and not enough to change the recommendation. (sources/HF-ESC-2026, sources/HF-AHA-2022)
• One narrow exception: gradual withdrawal may be considered (IIb/C) in highly selected patients with complete normalisation of LV function, volume and natriuretic peptides after treatment of a reversible cause. (sources/HF-ESC-2026)

Pathophysiology

• Neurohormonal activation. Reduced cardiac output triggers RAAS and sympathetic activation. Initially compensatory, chronic excess drives maladaptive remodelling — myocyte hypertrophy, apoptosis, interstitial fibrosis and progressive dilatation or stiffening. Natriuretic peptides are released in proportion to wall stress and serve as both load markers and therapeutic targets. (sources/HF-ESC-2021, rating: very high)
• Forward and backward failure. Forward failure (low output) produces fatigue and exercise intolerance; backward failure (raised filling pressures) produces pulmonary congestion in left-sided failure and raised JVP or peripheral oedema in right-sided failure. HFrEF is driven by reduced contractility and output; HFpEF by impaired relaxation and increased stiffness raising LVEDP at normal or near-normal volumes. (sources/HF-ESC-2021)
• Remodelling runs in opposite geometric directions. HFrEF shows eccentric dilatation from volume overload; HFpEF and HFmrEF show concentric hypertrophy from pressure or metabolic load. GDMT reverses eccentric remodelling — which is what produces the HFimpEF phenotype — but does not remove the underlying structural risk. (sources/HF-AHA-2022)
• Cardiorenal interaction. Venous congestion and reduced renal perfusion pressure both impair kidney function, and over two-thirds of advanced HF patients have kidney dysfunction. A creatinine rise during aggressive decongestion does not equate to tubular injury — do not reduce diuretics for eGFR decline alone. Full framework: concepts/Cardiorenal-Syndrome. (sources/AKI-HF-AHA-2024, rating: very high)
• Arrhythmic substrate. HF produces comprehensive ventricular ionic remodelling — ↑INaLate, ↑If, ↑NCX1, ↓IKr/IKs/Ito/IK1 — raising arrhythmic risk independently of LVEF and lowering repolarisation reserve, which is why QT-prolonging drugs carry elevated torsades risk in HF. Full detail: concepts/Electrical-Remodeling. (sources/membrane-potential-physrev-2021, rating: very high)

Diagnosis

Natriuretic peptides and structural criteria

• HFpEF requires LVEF ≥50% plus objective evidence of diastolic dysfunction or raised filling pressures plus elevated natriuretic peptides. The more abnormalities present, the higher the likelihood. Full diagnostic algorithms: entities/HFpEF. (sources/HF-ESC-2021, rating: very high)
• Up to 30% of HFpEF patients have normal natriuretic peptides, most often because of obesity — adipose tissue clears BNP. A normal value does not exclude the diagnosis. (sources/echo-hfpef-ase-2025, rating: very high)
• In borderline haemodynamics (PAWP 13–15 mmHg with HFpEF features), exercise or fluid challenge may be considered (Class IIb) to unmask occult post-capillary pulmonary hypertension. (sources/PHT-ESC-2022, rating: very high)

Cardiac troponin in decompensated heart failure

• Up to 90% of patients with acute HF have cTnT above the sex-specific 99th percentile URL, through ischaemia, supply–demand mismatch, apoptosis and autophagy, infiltrative and inflammatory injury, and neurohormone-driven injury; preload-induced stretch is a proposed non-ischaemic mechanism. (sources/5thMI-AHA-2026, rating: very high)
• Troponin and ECG on admission are recommended in new-onset or acutely decompensated HF, and serial measurement improves discrimination — but CAD and regional wall motion abnormalities are common baseline findings, so imaging is often needed before an ischaemic cause can be accepted or excluded. (sources/5thMI-AHA-2026)

Drug thresholds in chronic kidney disease

The eGFR at which each drug must be started or stopped is where most HF prescribing actually stalls. Cross-cutting thresholds are here; the phenotype-specific ordering is on concepts/HFrEF-Management and concepts/HFpEF-Management. (sources/CVD-CKD-ESC-2026, rating: very high)

• Irrespective of LVEF: loop diuretics I A and an SGLT2 inhibitor at eGFR ≥20 I A. Do not initiate an SGLT2 inhibitor below eGFR 20 or on dialysis, but continue it if already established and eGFR falls below 20 (IIa C).
• HFrEF: ACE inhibitor, ARNI or ARB and beta-blocker at eGFR ≥30 (I A each), falling to IIb C at eGFR 15–29; a steroidal MRA is I A at eGFR ≥30, and the benefit persists if eGFR later falls below 30. The guideline states plainly that no data exist below eGFR 15 or on dialysis. Digoxin, ivabradine and vericiguat each carry their own eGFR ceiling — see concepts/HFrEF-Management.
• HF with LVEF ≥40%: either a steroidal or a non-steroidal MRA at eGFR ≥25 (IIa B1) — though the text concedes the effect is smaller at LVEF >40% and smaller again at eGFR <60, and the FINEARTS-HF CKD subgroup hazard ratio of 0.91 crossed unity. Semaglutide or tirzepatide is IIa B1 at eGFR ≥15 in obese HFpEF.
• Decompensated HF with CKD: an SGLT2 inhibitor early in admission at eGFR >20 I B1; acetazolamide 500 mg IV for three days at eGFR ≥20 IIa B1 (ADVOR); a spot urinary sodium <70 mmol/L at 2 hours should prompt doubling the dose and twice-daily dosing (IIa B1); and continue decongestion despite a creatinine rise up to 50% where the diuretic response is good (I C). See concepts/Cardiorenal-Syndrome.
• Devices: primary-prevention ICD benefit attenuates below eGFR 60 (adjusted HR 0.49 at ≥60 versus 0.80 at <60, confidence interval crossing 1), CRT effect is not modified by CKD, and mitral TEER benefit is preserved. Durable mechanical support is not recommended with a baseline eGFR <30 unlikely to improve and no dual-organ option — III C.

Echocardiography

Resting echocardiography establishes the structural signature — chamber size, wall thickness, LA volume, diastolic grade, RV function — and excludes the alternative explanations that change management: significant valvular disease, HCM, constrictive pericarditis and cardiac amyloidosis. LVEF should be reported from a modality with adequate endocardial definition, and CMR is preferred when the EF is borderline or an infiltrative or inflammatory cause is suspected. Full diastolic algorithm: concepts/LV-Diastolic-Function. (sources/HF-ESC-2021, rating: very high)

Cardiac amyloidosis

• Suspicion triggers: LV wall thickness ≥14 mm with dyspnoea, fatigue or oedema; ECG-echo voltage discordance; aortic stenosis; carpal tunnel syndrome; spinal stenosis; polyneuropathy. (sources/HF-AHA-2022, rating: very high)
• Three-step work-up, each COR 1: screen for monoclonal light chains (serum/urine immunofixation plus free light chains) → if negative, bone scintigraphy (⁹⁹ᵐTc-PYP) to confirm ATTR-CM → if confirmed, TTR gene sequencing to separate hereditary ATTRv from wild-type ATTRwt. (sources/HF-AHA-2022)
• Full imaging criteria and pitfalls: concepts/Cardiac-Amyloidosis-Imaging and entities/ATTR-Amyloidosis.

Invasive haemodynamics

Right heart catheterisation is the reference standard when non-invasive assessment is equivocal, and it is required before transplant listing and for LVAD candidacy. It also defines the acute HF phenotypes — isolated LV failure, isolated RV failure and biventricular failure — and stages cardiogenic shock. All of that detail, including the HFpEF exercise criteria, LVAD ramp testing and the PAWP measurement pitfalls, sits on concepts/Right-Heart-Catheterization. (sources/rhc-hf-ehj-2025, rating: high)

Remote pulmonary artery pressure monitoring (CardioMEMS, Cordella) is established for NYHA II–III disease with recent hospitalisation or elevated natriuretic peptides: rising pressures precede clinical congestion by days to weeks, allowing proactive diuretic titration. See concepts/Right-Heart-Catheterization. (sources/hemodynamic-hf-pht-aha-2026, rating: very high)

Iron deficiency

Diagnose by transferrin saturation <20% or serum ferritin <100 μg/L. Applies to HFrEF and HFmrEF; intravenous iron is not currently recommended in HFpEF. (sources/HF-update-ESC-2023, rating: very high) Full evidence: concepts/Iron-Deficiency-in-HF.

Decompensated heart failure

The 2026 ESC guideline replaced "acute heart failure" with decompensated heart failure and split it into four clinical categories — decompensated left-sided heart failure, decompensated right-sided heart failure, acute pulmonary oedema, and cardiogenic shock. Management from presentation through the six-week post-discharge window is on concepts/Decompensated-HF-Management; the shock category in full is on concepts/Cardiogenic-Shock. (sources/HF-ESC-2026, rating: very high)

What belongs on this page is the fact that decompensation is where HF outcomes are decided, and the decisive interventions are in-hospital: an SGLT2 inhibitor started after stabilisation (I/B1), and rapid pre-discharge initiation and up-titration of foundational therapy with close follow-up over six weeks (I/B2 — STRONG-HF, readmission or death at 180 days 23.3% → 15.2%). The chronic pathway resumes when that window closes.

Advanced heart failure

• Definition: ≥2 episodes of congestion or low output in 12 months requiring IV therapy, NYHA III–IV, severe cardiac dysfunction (LVEF ≤30%, peak VO₂ <12 mL/kg/min), or ≥1 recent hospitalisation. (sources/HF-ESC-2021, rating: very high)
• Heart transplantation: Class I for advanced HF refractory to medical and device therapy; right heart catheterisation is required before listing (ISHLT Class 1) and repeated every 3–6 months until transplant. (sources/HF-ESC-2021, sources/rhc-hf-ehj-2025)
• Long-term LVAD (destination therapy) is a viable alternative when transplant is not an option. (sources/HF-ESC-2021)
• Transcatheter tricuspid-valve repair in advanced HF with severe TR: TRIC-I-HF (n=360) showed repair plus medical therapy superior on a hierarchical composite of death, HF hospitalisation and quality of life at one year (win ratio 2.42) and reduced death or HF hospitalisation through three years (HR 0.40; 95% CI 0.29–0.55). The standalone one-year survival endpoint was not significant (HR 0.74; 0.42–1.29) and secondary endpoints were unadjusted for multiplicity. Full detail: concepts/Tricuspid-Regurgitation. (sources/TRIC-I-HF-NEJM-2026, rating: very high)
• Kidney dysfunction affects over two-thirds of advanced HF patients. Serum creatinine is preferred over eGFR for day-to-day tracking; transkidney perfusion pressure (MAP − CVP) has a goal >60 mmHg; and a creatinine rise during decongestion does not equal tubular injury. The Heart-Kidney Profiles — A no dysfunction, B transient and reversible, C persistent requiring renal replacement — separate patients who will recover from those who will not. After LVAD, AKI occurs in 37%, with early eGFR improvement in 85% but sustained improvement in only 3.3%; peritoneal dialysis is preferred over haemodialysis in LVAD patients. Full framework: concepts/Cardiorenal-Syndrome. (sources/AKI-HF-AHA-2024, rating: very high)
• Transplant candidacy: evaluate every candidate with eGFR <45 mL/min/1.73 m² for simultaneous heart-kidney transplantation (UNOS criterion ≤30). Dialysis-requiring kidney failure occurs in 13.4% within 90 days of heart transplant, and a safety-net policy gives heart recipients priority deceased-donor kidney access at 60–365 days. (sources/AKI-HF-AHA-2024)
• Heart failure in kidney transplant recipients: HF prevalence in dialysis patients is 12–36 times the general population, with 83% three-year mortality after HF hospitalisation. De novo HF after transplant occurs in 10.2% at 12 months and 18.3% at 36 months, predicts death (HR 2.6) and graft failure (HR 2.7), and is as common as de novo ischaemic heart disease. Pre-transplant LVEF <45% independently predicts cardiac death (HR 4.8); pre-transplant sPAP >50 mmHg carries nearly four times the post-transplant mortality. (sources/cardiorenal-aha-2019, rating: very high)

Special populations

Clonal haematopoiesis

• Meta-analysis of 56,597 people without baseline HF found a 25% higher HF risk in CH carriers, independent of traditional risk factors and CAD. (sources/ch-aha-2026, rating: very high)
• The association is gene-specific rather than phenotype-wide: TET2 variants are 2.4-fold enriched in HFpEF, while ASXL1 CH tracks with modestly reduced EF. CH in established HF predicts higher all-cause mortality and more HF hospitalisations. Full gene-level mechanisms: concepts/Clonal-Hematopoiesis.

Cancer therapy-related cardiac dysfunction

• Graded by LVEF decline, GLS change and biomarker rise: asymptomatic mild = LVEF ≥50% with new GLS decline >15% and/or biomarker rise; moderate = LVEF 40–49% with ≥10 percentage-point decline; severe = LVEF <40%. (sources/Cardio-Oncology-ESC-2022, rating: very high)
• Standard HF therapy does double duty — ACEi/ARNi, beta-blockers, MRA and SGLT2i both treat established CTRCD and serve as cardioprotection in high-risk patients. Full severity-stratified algorithms, including the more permissive approach to continuing HER2-targeted therapy: concepts/Cardio-Oncology and concepts/Cancer-Therapy-Related-CV-Toxicity.

Pulmonary hypertension associated with left heart disease

• Post-capillary PH affects ≥50% of HFpEF patients, 60–70% of severe mitral valve disease and up to 50% of symptomatic aortic stenosis, and no approved therapy targets its pulmonary vascular component — PDE5 inhibitors are ineffective and riociguat failed. (sources/PHT-ESC-2022, rating: very high)
• Pulmonary-artery denervation (PADN-HF-PH) reduced two-year clinical worsening from 51.5% to 25.7% (HR 0.49; 95% CI 0.30–0.82; P=0.006) in Group 2 PH on contemporary GDMT, but the trial was open-label without sham control and the individual hard endpoints were null. Full appraisal: concepts/Pulmonary-Artery-Denervation and concepts/Pulmonary-Hypertension. (sources/padn-hf-ph-nejm-2026, rating: high)

Perioperative management

• Active decompensated HF is one of the four active cardiac conditions requiring treatment before noncardiac surgery, except in emergencies, and HF roughly triples 30-day perioperative mortality versus CAD alone. (sources/periop-aha-2024, rating: very high)
• Continue GDMT (COR 2a). ACEi/ARB may be held 24 hours before elevated-risk surgery if prescribed only for hypertension, but should be continued when prescribed for HFrEF. SGLT2i stop 3–4 days before surgery (COR 1) because of euglycaemic ketoacidosis risk — a deliberate, temporary interruption of a Class I therapy. (sources/periop-aha-2024)
• Full risk assessment and surveillance protocols: concepts/Perioperative-Cardiovascular-Assessment.

Obesity

• HF incidence rises 5% in men and 7% in women per unit of BMI, and obesity is more strongly associated with HFpEF than HFrEF (overweight +38%, class 1 obesity +56%). (sources/obesity-cv-aha-2021, rating: very high)
• The obesity paradox — better outcomes in overweight and class 1 obesity across HFrEF, HFpEF and acute HF — is observational and does not contradict the benefit of intentional weight loss. See concepts/Obesity-Paradox, entities/Obesity and entities/HFpEF.

Genetic testing and precision medicine

• COR 1, LOE B-NR: genetic screening and counselling for first-degree relatives of patients with confirmed inherited cardiomyopathy. COR 2a, LOE B-NR: genetic counselling and testing in selected nonischaemic cardiomyopathy. (sources/HF-AHA-2022, rating: very high)
• ICD consideration with LVEF >35% for high-risk pathogenic variants — LMNA, FLNC, desmosomal proteins, phospholamban. (sources/HF-AHA-2022)
• Six omics domains are mapped in the AHA 2019 statement on HF precision medicine: pathogenic variant yield varies by cardiomyopathy (HCM 60–70%, DCM 30–40%, ARVC 50–60%); pharmacogenomic variants in ADRB1, GRK5 and GNB3 modify beta-blocker response, and CYP2D6 poor metabolisers of metoprolol carry a fourfold bradycardia risk; epigenomic, proteomic, metabolomic and microbiomic markers remain research tools. (sources/HF-Precision-Medicine-AHA-2019, rating: high) See concepts/Pharmacogenomics-in-HF and concepts/Gut-Microbiome-in-HF.

Contradictions / Open Questions

• The AHA 2022 classification is still the one a large public health system runs on. The Hospital Authority handbook (Hong Kong), version-dated June 2026, lists all four categories — HFrEF ≤40%, HFmrEF 41–49%, HFpEF ≥50%, HFimpEF — with no mention of the ESC 2026 change, and its HFpEF therapy list stops at SGLT2i with ACE-I/ARB, ARNI and MRA only "to be considered." Its citation base is the 2021 ESC and 2022 AHA guidelines. Whether v9.1 predates the ESC 2026 publication or simply had not incorporated it cannot be settled from the document, but the operational point holds: the reclassification had not reached the guidance a hospital system issues. (sources/Handbook-HA-2024, rating: high)
• The classification divergence is a recommendation problem, not a labelling one. Neither guideline's evidence base was generated at LVEF 41–49%, so identical trial data produce two drugs in Europe and one in the United States. See Classification. (sources/HF-ESC-2026, sources/HF-AHA-2022, rating: very high)
• MRA in HFpEF: ESC 2026 Class I/A versus AHA 2022 COR 2b. The ESC upgrade rests on a meta-analysis pooling TOPCAT (neutral overall) with FINEARTS-HF (finerenone, LVEF >40%, positive). No trial of spironolactone in HFpEF has ever been positive, and TOPCAT's data-integrity problem is unresolved — so the strongest recommendation in HFpEF now rests on the weakest trial base of any foundational therapy. (sources/HF-ESC-2026, sources/spironolactone-hfpef-topcat-nejm-2014)
• SGLT2i reduces HF hospitalisation but not cardiovascular death across the preserved-EF spectrum. EMPEROR-Preserved and DELIVER both missed CV death individually, and the pooled estimate sits at HR 0.88 (P=0.052). The 2026 ESC Task Force states openly that it graded on the primary composite for this reason. (sources/HF-ESC-2026, sources/HF-update-ESC-2023)
• No HFpEF pharmacotherapy has reduced mortality — SGLT2i, finerenone, semaglutide and tirzepatide all improve hospitalisation or symptoms only. Whether this reflects competing non-cardiovascular mortality, disease heterogeneity, or simply underpowered follow-up is unresolved. Full discussion: entities/HFpEF.
• The 2026 HFrEF definition at LVEF 41–49% has no dedicated evidence. The Task Force notes no large prospective RCT has been performed exclusively in that band; the recommendations are extrapolated from HFrEF trials and from subgroup analyses. The ESC 2023 focused update's Class I SGLT2i recommendation for HFmrEF therefore survives only as an inference, not a trial result. (sources/HF-ESC-2026)
• HFimpEF duration of treatment is undefined. The AHA recommendation to continue GDMT indefinitely (COR 1) rests on a withdrawal study with six-month follow-up; no trial establishes how long treatment is needed, or whether any subgroup can safely stop. (sources/HF-AHA-2022)
• STRONG-HF may not generalise to optimised populations. It enrolled only patients not already on full doses of evidence-based therapy, and SGLT2 inhibitors were not in the protocol, so the incremental gain in a contemporary quadruple-GDMT population is unknown. (sources/HF-update-ESC-2023)
• IV iron: the Class I symptom recommendation is not supported by a positive pivotal trial. IRONMAN missed its primary endpoint and the upgrade rests on meta-analysis including a COVID-adjusted sensitivity analysis. HEART-FID, the largest trial, also missed its primary. (sources/HF-update-ESC-2023, sources/fe-hf-heartfid-nejm-2023, rating: very high; high)
• Advanced HF is defined by therapeutic refractoriness, not by a measurable threshold, so the boundary between Stage C and Stage D depends on what optimisation was actually attempted. This makes Stage D incidence, and therefore transplant and LVAD demand, hard to compare across centres. (sources/HF-ESC-2021, sources/HF-AHA-2022)

Connections

• Part of the HF family: entities/HFrEF — reduced-EF phenotype, foundational medical therapy and device therapy
• Part of the HF family: entities/HFpEF — preserved-EF phenotype, diagnostic algorithms and the outcome trials
• Related to entities/Hypertension — antecedent in 71% of HF; the leading modifiable cause of HFpEF
• Related to entities/Atrial-Fibrillation — shared substrate; AF drives decompensation and complicates rate control
• Related to entities/DCM, entities/LMNA and entities/TTN — the commonest nonischaemic cardiomyopathy, a high-risk genotype, and the reverse-remodelling genotype
• Related to entities/ATTR-Amyloidosis — infiltrative cause, 5–13% of HFpEF
• Related to concepts/Cardiorenal-Syndrome — kidney dysfunction in over two-thirds of advanced HF
• Related to concepts/Right-Heart-Catheterization — invasive haemodynamics, LVAD ramp testing, remote PA monitoring
• Related to concepts/LV-Diastolic-Function — the echocardiographic diastolic algorithm underpinning HFpEF diagnosis
• Related to concepts/Electrical-Remodeling — the ionic substrate linking HF to arrhythmia and sudden death
• Related to concepts/Pulmonary-Hypertension and concepts/Pulmonary-Artery-Denervation — Group 2 PH-LHD has no approved pulmonary-vascular therapy; PADN is the first adequately powered device trial
• Related to concepts/Secondary-Mitral-Regurgitation, concepts/Tricuspid-Regurgitation and concepts/Valvular-Heart-Disease — TEER in LVEF 20–50%, TRIC-I-HF in advanced HF, and valve disease as cause and consequence
• Related to concepts/Iron-Deficiency-in-HF — IV iron in HFrEF, redefined by TSAT <20%
• Related to concepts/Diuretic-Resistance — sequential nephron blockade and acetazolamide
• Related to concepts/Cardiac-Rehabilitation-HF and concepts/Heart-Healthy-Dietary-Patterns — exercise training and dietary sodium/potassium
• Related to concepts/Obesity-Paradox and concepts/Visceral-Adiposity — adiposity as risk factor, phenotype and prognostic modifier
• Related to concepts/Clonal-Hematopoiesis — 25% higher HF risk; TET2 enriched in HFpEF
• Related to concepts/Cardio-Oncology and concepts/Cancer-Therapy-Related-CV-Toxicity — CTRCD definitions and cardioprotection
• Related to concepts/Perioperative-Cardiovascular-Assessment — decompensated HF as an active cardiac condition
• Related to concepts/Pharmacogenomics-in-HF and concepts/Gut-Microbiome-in-HF — precision-medicine domains
• Related to concepts/CAM-in-Heart-Failure — omega-3 PUFA, yoga, and the agents to avoid
• Related to concepts/Myocardial-Viability — viability imaging does not predict revascularisation benefit
• Related to entities/ICD and entities/CRT — device therapy detail beyond the phenotype pages
• Related to entities/Vericiguat, entities/Sacubitril-Valsartan and entities/Cardiac-Glycosides — drug-level detail
• Related to entities/Takotsubo — an acute HF syndrome, not a benign one
• Related to entities/COPD — beta-blocker choice differs between HFrEF and HFpEF

Sources

• sources/HF-ESC-2026
• sources/HF-ESC-2021
• sources/HF-AHA-2022
• sources/HF-update-ESC-2023
• sources/HF-Precision-Medicine-AHA-2019
• sources/echo-hfpef-ase-2025
• sources/rhc-hf-ehj-2025
• sources/hemodynamic-hf-pht-aha-2026
• sources/PHT-ESC-2022
• sources/AKI-HF-AHA-2024
• sources/cardiorenal-aha-2019
• sources/TRIC-I-HF-NEJM-2026
• sources/padn-hf-ph-nejm-2026
• sources/spironolactone-hfpef-topcat-nejm-2014
• sources/finerenone-hfpef-fineartshf-nejm-2024
• sources/fe-hf-heartfid-nejm-2023
• sources/Cardio-Oncology-ESC-2022
• sources/ch-aha-2026
• sources/obesity-cv-aha-2021
• sources/periop-aha-2024
• sources/membrane-potential-physrev-2021
• sources/Handbook-HA-2024
• sources/5thMI-AHA-2026
• sources/CVD-CKD-ESC-2026