Clinical Cardiology · Heart Failure

The Second Universal Definition of Heart Failure: What Changes for Practice

A new joint consensus retires rigid ejection-fraction cutoffs, expands how clinicians classify the causes of heart failure, and reframes the syndrome as a dynamic rather than fixed diagnosis.

9-minute read · Physician education · Includes physician-investor context

A joint writing group representing the American Heart Association, the American College of Cardiology, the European Society of Cardiology, and the World Heart Federation has published the Second Universal Definition of Heart Failure.

The document updates and reaffirms the first universal definition published in 2021, which introduced pre-heart failure as stage B and standardized previously ambiguous terminology.

It is not a clinical practice guideline, but a shared vocabulary intended to align trials, registries, and day-to-day documentation across specialties.

For a cardiologist writing notes, coding encounters, or screening for enrollment eligibility, the changes are practical rather than theoretical.

Why the Ejection-Fraction Cutoffs Had to Go

The first universal definition relied on specific left ventricular ejection fraction thresholds to separate HF with reduced ejection fraction from HF with preserved ejection fraction.

The writing committee concluded that those cutoffs were arbitrary given the known variability of echocardiographic measurement of LVEF and unresolved debate over whether thresholds should differ by sex, age, or ethnicity.

The lower limit of normal LVEF is now cited as approximately 53% for women and 52% for men, with slightly higher thresholds among individuals of Asian descent, reinforcing that no single number applies uniformly.

The new document therefore collapses the classification into three clinically actionable groups: reduced, preserved, and improved ejection fraction, without anchoring to a specific numeric boundary.

Figure 1 · HF Trajectory Across Stages

Stage AAt risk

Stage BPre-HF

Stage CSymptomatic HF

Stage DAdvanced HF

Improvement
(LVEF rises, abnormalities persist)

Remission
(normalized LVEF, minimal symptoms)

Recovery
(sustained normalization — minority)

Reframing Cause: Eighteen Pathogenic Groups Instead of Two

Clinical practice has long sorted heart failure into just ischemic and nonischemic cardiomyopathy, a split the committee says omits the treatable causes of dilated and hypertrophic disease.

A patient whose underlying cause is cardiac amyloidosis, for instance, benefits from disease-targeted therapy well beyond standard heart failure management.

The new framework proposes a pathogenic classification independent of ejection fraction, spanning ischemic, hypertensive, valvular, arrhythmia-related, infiltrative, infective, inflammatory, toxic, heritable, pericardial, metabolic and nutritional, pregnancy-related, stress-induced, pulmonary or right-sided, congenital, high-output, other, and idiopathic causes.

The intent is to standardize how causes are recorded in registries and trials, since the same patient population can otherwise be labeled inconsistently across studies.

Table 1 · Stages in the Development and Progression of HF

Stage	Definition
A — At risk	Hypertension, atherosclerotic disease, diabetes, obesity, cardiotoxin exposure, or family history of cardiomyopathy, without symptoms, structural change, or elevated biomarkers.
B — Pre-HF	Structural or functional cardiac abnormality, or elevated natriuretic peptide or troponin, without current or prior symptoms.
C — HF	Current or prior symptoms or signs caused by a structural or functional cardiac abnormality.
D — Advanced HF	Severe symptoms at rest or minimal exertion, recurrent hospitalization despite guideline-directed therapy, or need for inotropes, mechanical support, transplantation, or palliative care.

HF with Improved Ejection Fraction Is Not a Cure

Patients whose previously reduced LVEF rises or normalizes on therapy are classified as HF with improved ejection fraction, a category first formalized in the 2022 heart failure guideline.

The document is explicit that improvement in EF does not equal disease resolution, and these patients remain at risk for recurrent left ventricular dysfunction, hospitalization, and sudden cardiac death.

Once a diagnosis of symptomatic heart failure is established, the individual is generally considered to carry that diagnosis permanently, even if the clinical picture improves substantially.

Practically, this means continued guideline-directed medical therapy and longitudinal surveillance rather than a taper toward discontinuation once an echocardiogram looks reassuring.

A related but distinct state, HF in remission, applies to select asymptomatic patients with normalized LVEF and stable biomarkers, while true recovery with sustained normalization of structure, function, and symptoms is reached by only a minority.

Worsening HF and Decompensated HF Are Now Distinguished

The consensus separates worsening HF, a progressive deterioration in symptoms or signs in a patient with an established diagnosis, from new-onset presentations or symptom flares driven by unrelated events such as infection or nonadherence.

Decompensated HF is defined more narrowly as the point at which treatment intensification is required, commonly an increase in diuretic dose, addition of combination diuretic therapy, or escalation to advanced interventions.

The distinction matters for documentation and for trial eligibility, since decompensation implies a treatment threshold rather than simply a worse-feeling patient.

Recognizing HF Mimics

The document devotes explicit attention to conditions that resemble heart failure without being pathophysiologically driven by myocardial neurohormonal activation.

Chronic kidney disease, third-trimester pregnancy, and obesity with deconditioning can all produce dyspnea, edema, and exertional limitation that mimic HF, sometimes accompanied by falsely reassuring natriuretic peptide levels.

Roughly half of the heart failure population across the ejection-fraction spectrum has coexisting coronary disease, and myocardial ischemia itself can serve as a mimic, a comorbid driver, or a trigger of decompensation.

Geography Still Shapes Cause

Ischemic heart disease accounts for more than half of HF cases across Western high-income and Eastern European regions but under 10% in sub-Saharan Africa, where hypertensive heart disease predominates instead.

Chagas disease remains a leading cause in parts of Latin America, while chronic obstructive pulmonary disease contributes disproportionately to HF prevalence in South and East Asia.

The committee also flags a near-absence of sub-Saharan African participants in major heart failure trials, a gap that limits how confidently global guidance can be generalized.

Figure 2 · Leading Contributors to HF Prevalence by Region (Illustrative, Global Burden of Disease-Derived)

50%+

Ischemic heart disease
Western / E. Europe

33%

Hypertensive disease
Sub-Saharan Africa

38%

COPD-related
South Asia

16%

Alcoholic CM
Eastern Europe

<10%

Ischemic disease
Sub-Saharan Africa

The GDMT and Company Landscape

None of the four pillars of guideline-directed medical therapy change under the new definition, but the reclassification affects which patients trial sponsors and payers consider eligible for these agents.

For physician-investors tracking the space, the table below summarizes representative agents, current approximate cash pricing, and the companies behind them.

Table 2 · Representative GDMT Agents and Market Context

Class / Agent	Brand	Approx. Cash Price (30-day)	Company (Ticker)
ARNI — sacubitril/valsartan	Entresto	~$600–700 brand; generic ~$45–90 with discount card; Medicare Part D negotiated ~$295	Novartis (NVS)
SGLT2 inhibitor — dapagliflozin	Farxiga	~$530–780 brand; GoodRx cash ~$288; generic available	AstraZeneca (AZN)
SGLT2 inhibitor — empagliflozin	Jardiance	~$360–830 brand; no generic; copay card as low as $0	Boehringer Ingelheim (private) / Eli Lilly (LLY)
Nonsteroidal MRA — finerenone	Kerendia	~$550–600 brand; manufacturer copay assistance available	Bayer (BAYRY)
Steroidal MRA — spironolactone	generic (Aldactone)	<$15 generic	Multiple generic manufacturers

Pricing is a snapshot subject to change, and it reflects list or cash pricing rather than what any individual patient pays after insurance, rebates, or Medicare Part D redesign under the Inflation Reduction Act.

This is general financial education, not personalized investment advice, and analyst views on any of these names can shift quickly around earnings and pipeline readouts.

What Actually Changes at the Bedside

Staging from stage A through stage D is unchanged, so risk-factor counseling and pre-HF surveillance workflows remain valid as written.

What changes is the language used when documenting ejection-fraction category and cause, favoring the simplified three-group EF framework and the expanded eighteen-category cause list over the old ischemic-versus-nonischemic shorthand.

Clinicians involved in trial screening or registry data entry should expect case-report forms to migrate toward this vocabulary over the next several guideline cycles.

Case Vignette

A 68-year-old with a history of anterior myocardial infarction and an LVEF that improved from 30% to 46% on quadruple guideline-directed therapy is told by a well-meaning relative that they are "cured."

Applying the second universal definition, this patient is correctly classified as HF with improved ejection fraction, not as a patient in remission or recovery, since residual scar and biomarker elevation persist.

The clinical implication is continuation of all four GDMT pillars, periodic re-imaging, and counseling that the diagnosis of heart failure remains permanent despite the reassuring echocardiogram.

Bottom Line

The second universal definition of heart failure moves away from rigid LVEF cutoffs toward three clinically actionable phenotypes, expands cause classification from two categories to eighteen, and reinforces that improvement in ejection fraction is not equivalent to cure.

Staging (A through D) and the core four-pillar GDMT approach are unchanged, but documentation language, trial eligibility criteria, and registry data fields are likely to evolve toward this new framework over time.

References

1. AHA/ACC/ESC/WHF Expert Consensus Document: Second Universal Definition of Heart Failure. Global Heart, 2026.
2. Second Universal Definition of HF Focuses on Phenotypes and Etiology. TCTMD, July 2026.
3. Universal Definition and Classification of Heart Failure: A Step in the Right Direction. American College of Cardiology, 2021.
4. Entresto Pricing and Savings. GoodRx, accessed 2026.
5. Farxiga vs. Jardiance: Comparing SGLT2 Inhibitors. GoodRx, 2026.

Disclaimer: This article is intended for physician education and general clinical discussion; it does not constitute individualized medical advice and should not replace clinical judgment or current society guidelines. Drug pricing and company information are provided for general financial education only, not as personalized investment advice; pricing is time-sensitive and subject to change, and past performance of any security does not predict future results. Consult a licensed financial advisor before making investment decisions.