2023 Focused Update of the 2021 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure

Authors, Journal, Affiliations, Type, DOI

• Authors: Theresa A. McDonagh & Marco Metra (co-chairs); ESC Task Force / Heart Failure Association
• Journal: European Heart Journal (2023) 44, 3627–3639
• Affiliations: King's College Hospital (London) & University of Brescia (Italy); pan-European multicentre
• Type: ESC Focused Interim Guideline Update (updates the 2021 ESC HF Guidelines)
• DOI: https://doi.org/10.1093/eurheartj/ehad195

Overview

This 2023 Focused Update revises the 2021 ESC Heart Failure Guidelines based on landmark RCTs published between the 2021 guideline and March 2023. The four key areas updated are: (1) SGLT2 inhibitors now receive Class I, Level A recommendations for both HFmrEF and HFpEF; (2) early empagliflozin in acute HF and rapid up-titration of oral therapies post-discharge; (3) SGLT2 inhibitors and finerenone for HF prevention in CKD + type 2 diabetes; (4) intravenous iron upgraded to Class I, Level A for symptoms/QoL in HFrEF and HFmrEF with iron deficiency.

Keywords

Guidelines · Acute heart failure · Comorbidities · Chronic kidney disease · Hospitalization · Diagnosis · Ejection fraction · Heart failure · Multidisciplinary management · Natriuretic peptides · Neurohormonal antagonists · Pharmacotherapy · Prevention

Key Takeaways

Chronic Heart Failure — HFmrEF and HFpEF (SGLT2 Inhibitors Upgraded)

• EMPEROR-Preserved (empagliflozin, n=5988, LVEF >40%): Reduced composite of CV death or HF hospitalization (HR 0.79, 95% CI 0.69–0.90; P<0.001). Effect driven by reduction in HF hospitalizations; no reduction in CV death. Independent of T2DM status.
• DELIVER (dapagliflozin, n=6263, LVEF >40%): Reduced CV death or worsening HF (HR 0.82, 95% CI 0.73–0.92; P<0.001). Benefit from reduction in worsening HF; no reduction in CV death. Benefit consistent across LVEF range including improved EF phenotype. Independent of T2DM.
• Meta-analysis of both trials: 20% reduction in CV death or first HF hospitalization (HR 0.80; P<0.001); HF hospitalization reduced 26% (HR 0.74; P<0.001). CV death not significantly reduced (HR 0.88; P=0.052).
• New Recommendation (HFmrEF): SGLT2 inhibitor (dapagliflozin or empagliflozin) — Class I, Level A to reduce HF hospitalization or CV death. (Upgraded from Class IIb/no recommendation in 2021)
• New Recommendation (HFpEF): SGLT2 inhibitor (dapagliflozin or empagliflozin) — Class I, Level A to reduce HF hospitalization or CV death. (New; no recommendation existed in 2021)
• The Task Force decided not to specify NT-proBNP thresholds for treatment (consistent with approach for other therapies in 2021 guidelines), though elevated natriuretic peptides are implicit in the HFpEF diagnosis.
• Terminology decision: the Task Force decided to retain "HFpEF" (not rename to HFnEF), deferring any terminology changes to the next full ESC HF guideline.

Acute Heart Failure — Diuretics

• ADVOR (acetazolamide + loop diuretics, n=519): Acetazolamide 500 mg i.v. added to standardized loop diuretics achieved successful decongestion in 42.2% vs. 30.5% with placebo (RR 1.46; P<0.001). Hospital stay 1 day shorter. No difference in HF rehospitalization or all-cause death. Further data on outcomes and safety required before guideline recommendation.
• CLOROTIC (hydrochlorothiazide + furosemide, n=230): Greater body weight reduction at 72h but no difference in dyspnoea, rehospitalization, or mortality. Serum creatinine rose more frequently with hydrochlorothiazide (46.5% vs. 17.2%). No guideline recommendation issued.

Acute Heart Failure — SGLT2 Inhibitors

• EMPULSE (empagliflozin in hospitalized acute HF, n stabilized after 3 days, 90-day follow-up): Primary endpoint of clinical benefit (hierarchical composite of death, HF events, KCCQ total symptom score) achieved in more patients with empagliflozin (win ratio 1.36, 95% CI 1.09–1.68; P=0.0054). Independent of LVEF and diabetes status. Adverse event rates similar between groups.
• Caution: SGLT2 inhibitors not indicated in type 1 diabetes; diabetic ketoacidosis risk in T2DM patients treated with insulin.

Acute Heart Failure — Management Strategy (STRONG-HF)

• STRONG-HF (n=1078, rapid up-titration of oral HF therapy pre-discharge, 6-week close follow-up): Trial stopped early for benefit. Primary outcome (HF readmission or all-cause death at 180 days) occurred in 15.2% (high-intensity care) vs. 23.3% (usual care) (aRR 0.66, 95% CI 0.50–0.86; P=0.0021). HF readmissions reduced (aRR 0.56; P=0.0011); all-cause death not significantly reduced alone.
• New Recommendation: Intensive strategy of initiation and rapid up-titration of evidence-based treatment before discharge AND during frequent follow-up in the first 6 weeks following HF hospitalization — Class I, Level B to reduce HF rehospitalization or death.
• Key monitoring during follow-up: symptoms/signs of congestion, blood pressure, heart rate, NT-proBNP, potassium, eGFR.
• Limitation: STRONG-HF was based on triple neurohormonal therapy; SGLT2 inhibitors not included in protocol but are incorporated into the recommendation based on EMPULSE/DELIVER/EMPEROR-Preserved evidence.

Comorbidities — CKD + Type 2 Diabetes Mellitus

• DAPA-CKD (dapagliflozin, CKD + diabetes/non-diabetes, n=4304, median follow-up 2.4 yr): Primary composite (eGFR decline ≥50%, end-stage kidney disease, or kidney/CV death) reduced 39% (HR 0.61; P<0.001). HF hospitalization or CV death reduced (HR 0.71; P=0.009).
• EMPA-KIDNEY (empagliflozin, broader CKD, n=6609, median follow-up 2.0 yr): Primary composite (kidney disease progression or CV death) reduced. HF hospitalization or CV death not significantly reduced (HR 0.84; P=0.15).
• Meta-analysis (SGLT2i across HF + CKD trials): HF hospitalization and CV death reduced by ~23% regardless of T2DM. In CKD-only trials, benefit significant in T2DM (HR 0.74) but not in non-T2DM patients (HR 0.95).
• FIDELIO-DKD + FIGARO-DKD (finerenone in diabetic CKD): Pooled analysis (n=13,026): CV composite reduced (HR 0.86; P=0.0018); HF hospitalizations alone reduced (HR 0.78; P=0.0030). Hyperkalaemia higher with finerenone.
• New Recommendations (T2DM + CKD):
  • SGLT2 inhibitors — Class I, Level A to reduce HF hospitalization or CV death
  • Finerenone — Class I, Level A to reduce HF hospitalization

Comorbidities — Iron Deficiency

• IRONMAN (ferric derisomaltose vs. usual care, HFrEF/HFmrEF with iron deficiency, n randomized, median 2.7 yr): Primary endpoint (total HF hospitalizations + CV death) rate ratio 0.82 (95% CI 0.66–1.02; P=0.070) — primary endpoint not met. Pre-specified COVID-adjusted analysis showed significant reduction (HR 0.76; P=0.047).
• Meta-analyses of IV iron in HF (including AFFIRM-AHF, IRONMAN, others — 10 trials, n=3373): IV iron reduced composite of total HF hospitalizations and CV death (RR 0.75, 95% CI 0.61–0.93; P<0.01); first HF hospitalization or CV death (OR 0.72; P=0.04). No effect on CV or all-cause mortality.
• New Recommendations (Iron Deficiency in HFrEF/HFmrEF):
  • IV iron supplementation — Class I, Level A to improve symptoms and QoL (upgraded from Class IIa in 2021)
  • IV iron (ferric carboxymaltose or ferric derisomaltose) — Class IIa, Level A to reduce HF hospitalization risk

Limitations of the Document

• STRONG-HF enrolled only patients not already on full doses of evidence-based therapies; results may not generalise to patients already optimally treated.
• HFpEF trials (EMPEROR-Preserved, DELIVER) demonstrated benefit in HF hospitalizations but no significant reduction in CV death — the guideline acknowledges this explicitly.
• DAPA-CKD and EMPA-KIDNEY enrolled mostly patients without established HF (~10% had prior HF); benefit in CKD without T2DM is less certain.
• IRONMAN primary endpoint not met; IV iron recommendation upgrades rely partly on meta-analysis data and COVID-adjusted sensitivity analysis.
• SGLT2 inhibitors not included in STRONG-HF protocol; their inclusion in the post-discharge recommendation is an extrapolation from other trials.

Key Concepts Mentioned

• concepts/HFpEF — SGLT2 inhibitor Class I recommendation; disease definition; NT-proBNP thresholds
• entities/Heart-Failure — full management update across HFrEF/HFmrEF/HFpEF

Key Entities Mentioned

• entities/Heart-Failure — updated management framework for all HF phenotypes
• entities/DCM — IV iron upgrade relevant to HFrEF management

Wiki Pages Updated

• wiki/sources/HF-update-ESC-2023.md (created)
• wiki/concepts/HFpEF.md (created)
• wiki/entities/Heart-Failure.md (created)
• wiki/entities/DCM.md (updated — IV iron upgrade, STRONG-HF post-discharge strategy)
• wiki/wikiindex.md (updated)
• wiki/log.md (appended)