Heart Failure · Guidelines
HFmrEF Is Gone, and the MRA Question Just Got Harder
The 2026 ESC heart failure guideline collapses three ejection fraction phenotypes into two, retires the term GDMT, renames acute heart failure, and issues a Class I recommendation for mineralocorticoid receptor antagonists across the LVEF spectrum that the steroidal trial data do not carry on their own.
The 2026 ESC Guidelines for the management of heart failure were released at ESC Congress 2026 and published simultaneously in the European Heart Journal, replacing the 2021 document and its 2023 focused update.
Four changes matter more than the rest: the ejection fraction categories, the staging framework, the vocabulary used for therapy, and a recommendation on mineralocorticoid receptor blockade that deserves closer reading than its class alone suggests.
Two phenotypes, not three
The category of heart failure with mildly reduced ejection fraction has been eliminated.
HFrEF is now defined by an LVEF below 50% with symptoms or signs of heart failure, and HFpEF by an LVEF of 50% or above with symptoms or signs plus objective evidence of structural or functional cardiac abnormality.
The stated rationale is that patients in the former 41–49% band share pathophysiology with lower ejection fractions and respond to the same therapies, which the accumulated subgroup data support reasonably well.
The practical effect is that a large group of patients who previously attracted a shrug and a Class IIb suggestion now fall inside a phenotype with four Class I drug classes attached.
One caveat deserves stating plainly: the relabelling does not move device thresholds, which remain anchored to their own specific ejection fraction cut-points rather than to the phenotype name.
Acute becomes decompensated
The guideline replaces acute heart failure with decompensated heart failure, on the reasoning that most presentations reflect gradual failure of compensation rather than sudden onset.
Alongside this, a four-stage framework running from A to D is adopted, spanning risk factors without structural disease, structural disease without symptoms, symptomatic disease, and advanced disease.
The staging language aligns European practice with the American approach and shifts attention toward the two stages where nothing has happened yet.
GDMT is retired for a three-tier scheme
The single term guideline-directed medical therapy has been split into three named tiers.
Foundational medical therapy covers agents with Class I recommendations and convincing morbidity or mortality benefit in broad populations.
Additional medical therapy covers everything recommended at Class IIa or IIb, plus Class I recommendations that apply only to specific subsets or to symptoms.
Guideline-directed interventional therapy covers devices and procedures.
Foundational therapy for HFrEF comprises beta-blockers, an ACE inhibitor, ARNI, or ARB, a mineralocorticoid receptor antagonist, and an SGLT2 inhibitor.
Foundational therapy for HFpEF comprises a mineralocorticoid receptor antagonist and an SGLT2 inhibitor, which is the first time the preserved phenotype has been given a defined foundation at all.
Uptitration of foundational therapy at least every one to two weeks toward target doses carries Class I, at Level C, which is an admission that the interval is consensus rather than trial-derived.
The MRA recommendation and the trials beneath it
Mineralocorticoid receptor antagonists now carry Class I in chronic heart failure irrespective of ejection fraction, which reads as the single boldest statement in the document.
The steroidal agents do not support that statement on their own.
TOPCAT was neutral overall for spironolactone in preserved ejection fraction, rescued only by a regional subgroup analysis that has been debated ever since.
SPIRIT-HF did not demonstrate benefit for spironolactone in the preserved and mildly reduced range, with enrolment difficulties limiting its interpretation.
The positive trial is FINEARTS-HF, which randomised 6,001 patients with heart failure and an LVEF of 40% or above to the nonsteroidal agent finerenone or placebo.
Over a median 32 months the composite of worsening heart failure events and cardiovascular death fell from 1,283 to 1,083 events, a rate ratio of 0.84 with a confidence interval of 0.74 to 0.95.
The benefit was carried by worsening heart failure events rather than by cardiovascular death, which differed by 8.1% against 8.7% and did not reach significance, and all-cause mortality was unchanged.
| Trial | Agent | Population | Result |
|---|---|---|---|
| TOPCAT | Spironolactone | LVEF ≥ 45% | Neutral overall; regional subgroup contested |
| SPIRIT-HF | Spironolactone | Preserved and mildly reduced | No demonstrated benefit; enrolment limited |
| FINEARTS-HF | Finerenone | LVEF ≥ 40%, n = 6,001 | Composite RR 0.84 (0.74–0.95); driven by worsening HF events |
A class-wide Class I recommendation therefore sits on top of one positive trial of one nonsteroidal molecule, while the agents most clinicians will actually reach for are the two that failed or came close to failing.
Cost sharpens the problem, since generic spironolactone runs around ten dollars a month and finerenone runs roughly seven hundred, which means the recommendation and the prescription will diverge in a large fraction of practices.
Hyperkalaemia is manageable but not trivial, with potassium above 5.5 mmol/L in the finerenone arm at roughly twice the placebo rate, against a reciprocal reduction in hypokalaemia.
The defensible reading is that the Class I recommendation is a statement about mineralocorticoid receptor blockade as a mechanism, not an assertion that the three available agents are interchangeable across the ejection fraction range.
SGLT2 inhibition becomes universal
SGLT2 inhibitors now carry Class I in preserved ejection fraction as well as reduced, extending a recommendation that was previously confined to one end of the spectrum.
This is the least controversial change in the document, and it converts the drug class into the one agent appropriate for essentially every heart failure patient without a contraindication.
The obesity phenotype gets a drug
Semaglutide and tirzepatide receive Class IIa in preserved ejection fraction with obesity, formalising a phenotype that had no targeted therapy at all two years ago.
The SUMMIT trial randomised 731 patients with a mean BMI of 38 kg/m², reporting cardiovascular death or worsening heart failure in 9.9% on tirzepatide against 15.3% on placebo, a hazard ratio of 0.62.
Symptom benefit was substantial at a 6.9-point improvement in the Kansas City Cardiomyopathy Questionnaire summary score at 52 weeks.
Separately, GLP-1 receptor agonists are recommended at Class IIa in type 2 diabetes with additional cardiovascular risk factors to reduce incident heart failure or cardiovascular death.
Devices, advanced disease, and the smaller upgrades
Early referral to a specialist centre for transplantation or mechanical circulatory support assessment now carries Class I, which converts a judgement call into an obligation with a date attached.
Durable mechanical circulatory support and transcatheter mitral valve repair both move up, reflecting device iteration and trial accumulation rather than any single result.
Cardiac resynchronisation therapy should be considered in preference to right ventricular pacing in reduced ejection fraction with high-degree AV block, at Class IIa.
Digoxin rises to Class IIa for symptomatic patients with LVEF at or below 40% despite optimal foundational therapy, a modest rehabilitation of an old drug.
Vericiguat holds at Class IIb for symptomatic HFrEF below 45% despite optimal foundational therapy.
| Agent | Brand · Manufacturer | Position in 2026 | Approximate US cash cost |
|---|---|---|---|
| Finerenone | Kerendia · Bayer (OTC: BAYRY) | Nonsteroidal MRA carrying the preserved-EF evidence | Roughly $690–800 monthly — GoodRx |
| Spironolactone | Generic, multiple | Steroidal MRA; the affordable option with the weaker preserved-EF data | Around $10 monthly |
| Dapagliflozin | Farxiga · AstraZeneca (NASDAQ: AZN) | Foundational across both phenotypes | Commonly $250–450 monthly — GoodRx |
| Empagliflozin | Jardiance · Boehringer Ingelheim and Eli Lilly (NYSE: LLY) | Foundational across both phenotypes | Around $250 with a discount card — GoodRx |
| Sacubitril/valsartan | Entresto · Novartis (NYSE: NVS) | Foundational RAAS option in HFrEF | Wide spread by pharmacy; generic now listed — GoodRx |
| Tirzepatide | Zepbound · Eli Lilly (NYSE: LLY) | Class IIa in preserved EF with obesity | Self-pay around $299 monthly — GoodRx |
| Semaglutide | Wegovy · Novo Nordisk (NYSE: NVO) | Class IIa in preserved EF with obesity | Self-pay tiers via NovoCare |
Pricing moves frequently and every figure above should be treated as approximate rather than quoted to a patient.
Case scenario
A 68-year-old man is referred with exertional dyspnoea, a BMI of 36 kg/m², type 2 diabetes, and an echocardiogram reporting an LVEF of 44% with grade 2 diastolic dysfunction and an indexed left atrial volume of 40 mL/m².
Under the 2021 framework he is labelled HFmrEF, receives a diuretic, and attracts a Class IIb conversation about whether the neurohormonal agents are worth starting.
Under the 2026 framework he is HFrEF, and all four foundational classes are indicated from the first visit rather than considered.
The plan is an SGLT2 inhibitor and a low-dose beta-blocker at visit one, sacubitril/valsartan and a mineralocorticoid receptor antagonist added over the following month, with review every one to two weeks and potassium and creatinine checked at each step.
His obesity is treated as a target rather than a comorbidity, and because his ejection fraction sits below 50% the incretin recommendation applies to his diabetes risk profile rather than to a preserved-EF indication, which is a distinction worth documenting so the next clinician understands the reasoning.
What changes on Monday
Rewrite the echo report interpretation macro, because an LVEF of 44% now names a phenotype with four indicated drug classes rather than a diagnostic grey zone.
Replace the phrase GDMT in local order sets and letters with the foundational, additional, and interventional tiers, since the whole point of the new vocabulary is that it tells the reader whether a drug is a cornerstone or an add-on.
Decide institutional policy on which mineralocorticoid receptor antagonist the Class I recommendation means at each ejection fraction, because the answer is not the same drug across the range and the cost difference is seventy-fold.
Book the uptitration visits at the time of discharge rather than leaving them to a routine follow-up interval that will not meet a one-to-two-week cadence.
Treat a Class I referral to an advanced heart failure centre as a referral, not as a topic for the next clinic letter.
References
- 2026 ESC Guidelines for the management of heart failure. European Heart Journal, August 2026. Oxford Academic
- ESC clinical practice guidelines hub — heart failure, with slide set and patient versions. escardio.org
- Major changes made to the ESC guidelines on heart failure. ESC press release, August 2026. escardio.org
- FINEARTS-HF: finerenone in heart failure with LVEF ≥ 40%. ESC press release. escardio.org
- SUMMIT: tirzepatide in HFpEF with obesity. TCTMD. tctmd.com
- Beyond steroidal MRAs: rethinking mineralocorticoid receptor blockade in heart failure. American College of Cardiology. acc.org
Further viewing
- 2026 ESC Guidelines for the management of heart failure
- Optimisation of heart failure therapy — what's new from ESC
- 2026 ACC expert consensus decision pathway on HFpEF
Educational content for clinicians; not a substitute for the full guideline text or for individual clinical judgement. Recommendation classes and evidence levels are summarised from the published document and contemporaneous reporting, and the primary text should be consulted before implementation. Pricing is approximate, varies by pharmacy and coverage, and changes frequently. The case scenario is fictional and contains no patient identifiers.
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.