Prognosis of "pre-heart failure" clinical phenotypes
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Updated: Dec 24, 2025

A Surgical Model of Heart Failure with Preserved Ejection Fraction in Tibetan Minipigs
Published on: February 18, 2022
Raghava S Velagaleti1,2, Meghan I Short3, Martin G Larson1,3
1Framingham Heart Study, Framingham, Massachusetts, United States of America.
Insights
Individuals with partial heart failure (HF) symptoms face significant risks for developing definite HF, cardiovascular disease, and mortality. Early recognition and management are crucial for improving outcomes in these patients.
Area of Science:
- Cardiology
- Clinical Medicine
- Epidemiology
Background:
- Heart failure (HF) diagnosis can be challenging, with varying certainty.
- The long-term prognosis for individuals with subclinical or undiagnosed HF is not well understood.
Purpose of the Study:
- To evaluate the natural history of individuals with suspected heart failure but uncertain diagnostic certainty.
- To compare the risks of cardiovascular disease (CVD) events and mortality between different HF diagnostic certainty groups and controls.
Main Methods:
- Framingham Heart Study data (1990-2009) were used, categorizing suspected HF into definite, possible, and probable groups.
- Multivariable-adjusted Cox regression analysis compared outcomes between HF groups and age/sex-matched controls without HF or CVD.
- Outcomes assessed included incident definite HF, coronary heart disease (CHD), other CVD, and death.
Main Results:
- Individuals with possible or probable HF showed significantly higher hazards for definite HF, CHD, other CVD, and death compared to controls.
- The risk of adverse outcomes in possible/probable HF groups was comparable to that of the definite HF group.
- The probable HF group had a higher risk of progressing to definite HF than the possible HF group, but a lower risk of death.
Conclusions:
- Individuals meeting partial criteria for heart failure face substantial risks for progression to overt HF, CVD, and mortality.
- These findings underscore the importance of recognizing and managing patients with even subtle signs of HF.
- Prognostic stratification within uncertain HF diagnoses may inform clinical decision-making.
Background:
Heart failure (HF) is a clinical syndrome where diagnostic certainty varies. The prognosis of individuals with some clinical features of HF, but without the fully overt syndrome, is unclear. Therefore, we sought to evaluate their natural history.
Methods And Results:
Between 1990 and 2009, all suspected HF cases in the Framingham Heart Study were adjudicated into 3 groups reflecting varying diagnostic certainty: definite (meeting HF diagnostic criteria; n = 479), possible (meeting HF criteria but with an alternative explanation for findings; n = 135), and probable (insufficient criteria for definite HF; n = 121) HF. Age-and-sex-matched individuals (n = 1112) without HF or cardiovascular disease (CVD) were controls. Using multivariable-adjusted Cox regression, we compared the possible/probable HF groups with controls regarding risk of incident definite HF, coronary heart disease (CHD), other CVD or death; and with definite HF regarding risk of latter three outcomes. During follow-up (mean 8.6 years), ~90% of individuals with possible, probable and definite HF experienced CVD events or died. Compared with controls, those with possible or probable HF experienced higher hazards for definite HF, CHD, other CVD and death (hazards ratios [HR] 1.35-9.31; p<0.05). The possible/probable groups did not differ from the definite HF group for risk of any outcome. Compared with the possible HF group, the probable HF group had a higher propensity for definite HF (HR 1.64, with a higher proportion of ischemic HF) but lower risk of death (HR 0.69).
Conclusions:
Individuals meeting partial criteria for HF are at a substantial risk for progression to HF, CVD, and mortality.
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