In 1789, Jeremy Bentham published his Introduction to the Principles of Morals and Legislation, proposing that human wellbeing could be rationally quantified through a felicific calculus — a systematic account of pleasure and pain across several dimensions, including intensity, duration, and certainty. Bentham held that what cannot be measured cannot be managed. Two centuries later, cardiology has arrived, somewhat reluctantly, at the same conclusion: the suffering of our patients — the fatigue, the breathlessness, the anxiety, the social withdrawal — demands structured quantification if we are to take it seriously as a therapeutic target. This very issue has been at the center of the development of patient-reported outcome measures (PROMs). The analysis by Aguiar-Neves et al., published in this issue, is precisely this kind of rigorous account.1 Drawing on data from the HOMAGE trial — conducted in individuals with a left ventricular ejection fraction (LVEF) ≥ 45%, elevated natriuretic peptides (NPs) and established coronary artery disease, or increased cardiovascular (CV) risk, but without a formal heart failure (HF) diagnosis — the authors characterize the health status of 519 participants and explore whether spironolactone might influence it.2 The findings are enlightening with regard to our collective failure to recognize HF before it reaches the clinical threshold.

The EQ-5D-3L, with its five dimensions, is an internationally validated instrument for mapping patient wellbeing. The median EQ European index in this cohort was 0.78 (interquartile range [IQR] 0.71–1.00), with 42% of participants reporting optimal health status (EQ index=1) and 24% falling into the poor health status category (EQ index < 0.71). For context: published population norms for European adults aged 70–79 years yield an EQ-5D-3L index of approximately 0.74–0.84, according to country.3 The median HOMAGE value does not, therefore, differ substantially from the general population of comparable age — and therein lies a disquieting observation. These patients had elevated NPs, established CV disease, and echocardiographic abnormalities, yet reported quality of life (QoL) broadly similar to healthy age-matched peers. This probably reflects adaptation, typically seen in these populations. Patients recalibrate their expectations downward to accommodate their illness, normalizing functional limitations that should prompt earlier clinical attention — a stark reminder of the clinical need to use validated, objective markers of functional capacity, as is done, for instance, in pulmonary arterial hypertension with the six-minute walk test. In fact, a global score of 0.78 may conceal a specific and treatable problem: the burden of a disease that causes progressive exertional dyspnea or fatigue that has silently curtailed their daily walk. Therefore, the dimensional structure of the EQ-5D is clinically indispensable.

Eventually, the most provocative finding of this study is epidemiological and nosological. The authors observe, with caution, that the combination of symptoms (one in three participants reporting exertional breathlessness; 16% fulfilling self-reported New York Heart Association (NYHA) class ≥ II criteria), elevated NPs levels, and echocardiographic abnormalities renders it likely that a significant proportion of enrolled patients already had clinical HF, albeit undiagnosed. This observation deserves to be stated more forcefully. Recently, the PORTHOS study, conducted in a representative community-based sample of Portuguese adults aged ≥ 50 years, found that HF affects approximately one in six individuals in this age group, with an estimated prevalence of 16.5%. Critically, 90% were previously undiagnosed.4 Read together, HOMAGE and PORTHOS deliver an unambiguous message: our capacity to identify HF before hospitalization is profoundly inadequate. NYHA classification, as assessed by a clinician in a brief outpatient encounter, is notoriously insensitive to behavioral adaptation. Patients, for example, who had stopped climbing stairs, no longer report dyspnea on exertion, because they have learned to avoid exertion. Consequently, PROMs are demonstrably more sensitive. The EQ-5D and the HOMAGE symptom questionnaire captured significant functional impairment in patients who, at a conventional clinical interview, considered themselves asymptomatic. A paradigm shift is required as probably, instead of asking patients whether they experience breathlessness, we should ask whether they climb stairs, whether they walked last week, or whether they needed to pause mid-task in activities they previously completed without difficulty.

In this context, the consistent association between galectin-3 and declining health status across multiple EQ-5D domains acquires particular clinical resonance. Galectin-3, secreted by activated macrophages, mediates cardiac fibrosis through fibroblast proliferation and collagen deposition.5 Its association with health status deterioration — independent of NT-proBNP, LVEF, and conventional clinical variables — suggests that it captures a pathophysiological dimension that hemodynamic biomarkers do not register: the cumulative fibrotic burden and subclinical patients feel progressively worse but resting hemodynamics have not yet changed sufficiently to explain why. Therefore, a provocative question follows: could galectin-3, in combination with NT-proBNP and structured PROMs, form the basis of a community screening strategy for undiagnosed HF? The PORTHOS study demonstrated that NT-proBNP-based point-of-care testing, followed by echocardiographic confirmation, achieves high diagnostic yield in community settings.4 Galectin-3 might enrich this pipeline by identifying patients at highest risk of functional deterioration — those in whom fibrosis is already progressing, even before filling pressures are appreciably elevated. This remains a hypothesis in need of prospective validation; it is, however, mechanistically grounded and scientifically compelling.

It is important to acknowledge that the HOMAGE cohort — 75% male with coronary artery disease in approximately 70% of participants — represents the classic HF with reduced ejection fraction risk phenotype, not the HFpEF-susceptible Stage B HF patient. The prototypical candidates for pre-HFpEF prevention trials are older women who are obese, have hypertension, with atrial fibrillation, type 2 diabetes, or chronic kidney disease.6 The observation that women and obese participants carry the worst quality-of-life scores within HOMAGE is itself an important signal: the study captured, at its margins, the phenotype that should have been its center. Future prevention trials must stratify by phenotype, actively recruit women with cardiometabolic risk factors, and either exclude — or explicitly characterize and stratify — patients with early unrecognized HF.

The absence of any QoL benefit with spironolactone is now, in the light of the most recent evidence, definitively contextualized. The recently presented SPIRIT-HF trial randomized 730 patients with HFpEF or HF with mildly reduced ejection fraction to spironolactone or placebo over 24 months across 56 European centers.7 The primary composite endpoint (HF hospitalization and cardiovascular death) did not differ between groups, and the spironolactone arm exhibited an unexpected increase in total hospitalizations, hyperkalemia, and hypotension. A pre-specified meta-analysis pooling SPIRIT-HF with the Americas cohort of TOPCAT confirmed the absence of clinical benefit. It is probable that, with SPIRIT-HF, the chapter of spironolactone in HFpEF and at-risk populations appears to close — both in terms of clinical outcomes and, as HOMAGE confirms, patient-reported wellbeing. The Aldo-DHF trial8 had already established that although spironolactone improves diastolic parameters, it does not translate structural gains into symptomatic benefit. The constructive horizon now belongs to finerenone: FINEARTS-HF demonstrated a 16% relative reduction in the composite of cardiovascular death and total HF events,9 and its distinct pharmacological profile warrants dedicated testing in adequately phenotyped pre-clinical populations, with QoL prospectively registered as a co-primary endpoint.

The most enduring contribution of this analysis is methodological and programmatic. PROMs in HF prevention serve two irreplaceable functions. First, they unmask symptoms in patients who consider themselves asymptomatic — silent patients who have reorganized their lives around their limitations without recognizing these limitations as a disease. HOMAGE demonstrates that structured wellbeing instruments can identify the symptomatic patients that clinical unawareness perpetuates. Second, QoL trajectories provide a high-resolution window onto disease progression that event-driven endpoints cannot capture. Patients who neither die nor require hospitalization may nonetheless be experiencing progressive functional decline, social withdrawal, and diminishing autonomy. The 2022 AHA/ACC/HFSA Heart Failure Guidelines elevated QoL to a Class I therapeutic target.10 Prevention trials must follow this lead: pre-registering PROMs as primary endpoints, rather than treating them as post-hoc secondary analyses. Only then can we ensure that the preservation of lived experience carries the same scientific weight as the avoidance of hospitalization.

Bentham believed that the measure of a good society was the aggregate wellbeing of its members. The same standard should govern cardiovascular prevention: our aim is not simply to defer events, but to preserve function, autonomy, and the capacity for a life lived on the patient's own terms. The HOMAGE analysis shows that in high-risk populations, symptomatic burden is substantial, measurable, and largely invisible to conventional clinical assessment. Future trials must be designed accordingly — with PROMs registered prospectively as primary endpoints, phenotypes aligned with the true HFpEF demographics, and biomarkers such as galectin-3 tested as screening tools in the community. A single question in an outpatient consultation is a poor substitute for a validated questionnaire. It is time we act on that knowledge.