Related Experiment Video
Updated: Jul 25, 2025
Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
Clinical Characteristics and Outcomes in Patients With Heart Failure: Are There Thresholds and Inflection Points in
Toru Kondo1,2, Pooja Dewan1, Inder S Anand3
1British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (T.K., P.D., P.S.J., J.J.V.M.).
Insights
This study found a left ventricular ejection fraction (LVEF) threshold around 40-50% in heart failure (HF) patients, impacting characteristics and outcomes. These findings support current HF classification thresholds based on prognosis.
Area of Science:
- Cardiology
- Clinical Medicine
- Heart Failure Research
Background:
- Current heart failure (HF) classification relies on left ventricular ejection fraction (LVEF) categories.
- The biological rationale for established LVEF thresholds in HF remains under investigation.
Purpose of the Study:
- To investigate if LVEF thresholds exist in patient characteristics and clinical outcomes.
- To evaluate the biological rationality of current HF classification guidelines based on LVEF.
Main Methods:
- A merged dataset of 33,699 participants from 6 HF randomized controlled trials was analyzed.
- Poisson regression models assessed the relationship between LVEF and clinical outcomes, including death and HF hospitalization.
Main Results:
- Patient characteristics changed significantly around an LVEF of 50% as LVEF increased.
- Clinical outcomes, including all-cause death and HF hospitalization, showed inflection points around LVEF thresholds of 35-50%.
- No adverse outcomes were observed in patients with high-normal LVEF.
Conclusions:
- A distinct LVEF threshold of approximately 40-50% was identified, influencing patient characteristics and event rates.
- Findings support the current upper LVEF thresholds used for classifying HF with mildly reduced ejection fraction based on prognosis.
Background:
Recent guidelines proposed a classification for heart failure (HF) on the basis of left ventricular ejection fraction (LVEF), although it remains unclear whether the divisions chosen were biologically rational. Using patients spanning the full range of LVEF, we examined whether there was evidence of LVEF thresholds in patient characteristics or inflection points in clinical outcomes.
Methods:
Using patient-level information, we created a merged dataset of 33 699 participants who had been enrolled in 6 randomized controlled HF trials including patients with reduced and preserved ejection fraction. The relationship between the incidence of all-cause death (and specific causes of death) and HF hospitalization, and LVEF, was evaluated using Poisson regression models.
Results:
As LVEF increased, age, the proportion of women, body mass index, systolic blood pressure, and prevalence of atrial fibrillation and diabetes increased, whereas ischemic pathogenesis, estimated glomerular filtration rate, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) decreased. As LVEF increased >50%, age and the proportion of women continued to increase, and ischemic pathogenesis and NT-proBNP decreased, but other characteristics did not change meaningfully. The incidence of most clinical outcomes (except noncardiovascular death) decreased as LVEF increased, with a LVEF inflection point of around 50% for all-cause death and cardiovascular death, around 40% for pump failure death, and around 35% for HF hospitalization. Higher than those thresholds, there was little further decline in the incidence rate. There was no evidence of a J-shaped relationship between LVEF and death; no evidence of worse outcomes in patients with high-normal ("supranormal") LVEF. Similarly, in a subset of patients with echocardiographic data, there were no structural differences in patients with a high-normal LVEF suggestive of amyloidosis, and NT-proBNP levels were consistent with this conclusion.
Conclusions:
In patients with HF, there was a LVEF threshold of around 40% to 50% where the pattern of patient characteristics changed, and event rates began to increase compared with higher LVEF values. Our findings provide evidence to support current upper LVEF thresholds defining HF with mildly reduced ejection fraction on the basis of prognosis.
Registration:
URL: https://www.
Clinicaltrials:
gov; Unique identifiers: NCT00634309, NCT00634400, NCT00634712, NCT00095238, NCT01035255, NCT00094302, NCT00853658, and NCT01920711.
More Related Videos
Related Concept Videos
01:30Heart Failure IV: Classification and Diagnostic Evaluation
01:17Pathophysiology of Heart Failure
01:26Heart Failure III: Clinical Manifestations
01:27Heart Failure I: Introduction
01:30Heart Failure VII: Nursing Interventions
01:29Heart Failure II: Pathophysiology