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Updated: Jul 30, 2025
Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
Echocardiographic Features Beyond Ejection Fraction and Associated Outcomes in Patients With Heart Failure With
Anthony E Peters1,2, Robert M Clare2, Karen Chiswell2
1Division of Cardiology, Duke University School of Medicine, Durham, NC (A.E.P., G.M.F., A.K., R.M., A.D.D.).
Insights
Left ventricular global longitudinal strain (LV GLS) is a key predictor of mortality in heart failure (HF) patients with preserved or mildly reduced ejection fraction. Abnormal LV GLS indicates higher mortality risk and comorbidity burden, regardless of LVEF.
Area of Science:
- Cardiology
- Echocardiography
- Heart Failure Research
Background:
- Current heart failure (HF) guidelines rely on left ventricular ejection fraction (LVEF) for patient classification and treatment.
- LVEF alone may not fully characterize HF patients, particularly those with mildly reduced or preserved LVEF.
- Limited data exist on the utility of echocardiographic parameters beyond LVEF in HF with preserved or mildly reduced LVEF.
Purpose of the Study:
- To evaluate the association of specific echocardiographic metrics with mortality in patients with HF with mildly reduced or preserved LVEF.
- To identify key echocardiographic predictors of adverse outcomes in this patient population.
- To explore the clinical significance of left ventricular global longitudinal strain (LV GLS) in HF management.
Main Methods:
- Retrospective analysis of 2337 patients with HF with mildly reduced or preserved LVEF from a US health care system (2017-2020).
- Assessment of LV global longitudinal strain (LV GLS), left atrial volume index, left ventricular hypertrophy (LVH), and E/e' ratio in relation to all-cause mortality.
- Multivariable regression modeling incorporating demographic factors, comorbidities, and echocardiographic features to determine independent predictors of mortality.
Main Results:
- Univariate analysis revealed significant associations between E/e', LV GLS, and left atrial volume index with 3-year all-cause mortality.
- In multivariable analysis, abnormal LV GLS (HR, 1.35; P=0.002) was independently associated with increased all-cause mortality.
- Approximately 40% of patients with LVEF >55% exhibited abnormal LV GLS, demonstrating a higher comorbidity burden and event rates.
Conclusions:
- Echocardiographic parameters, particularly LV GLS, are associated with adverse outcomes in HF patients irrespective of LVEF.
- Abnormal LV GLS identifies a significant subgroup of patients with HF with preserved or mildly reduced LVEF who have increased mortality risk.
- LV GLS may be a crucial metric for identifying high-risk patients and guiding future therapeutic strategies and clinical studies in HF.
Background:
Heart failure (HF) guidelines recommend assessment of left ventricular ejection fraction (LVEF) to classify patients and guide therapy implementation. However, LVEF alone may be insufficient to adequately characterize patients with HF, especially those with mildly reduced or preserved LVEF. Recommendations on additional testing are lacking, and there are limited data on use of echocardiographic features beyond LVEF in patients with heart failure with mildly reduced or preserved LVEF.
Methods:
In patients with HF with mildly reduced or preserved LVEF identified in a large US health care system, the association of the following metrics with mortality was evaluated: LV global longitudinal strain (LV GLS>-16), left atrial volume index (>28 mL/m2), left ventricular hypertrophy (LVH), and E/e´>13 and e´<9. A multivariable model for mortality was constructed including age, sex, and key comorbidities followed by stepwise selection of echocardiographic features. Characteristics and outcomes of subgroups with normal versus abnormal LV GLS and LVEF were evaluated.
Results:
Among 2337 patients with complete echocardiographic data assessed between 2017 and 2020, the following features were associated with all-cause mortality on univariate analysis over 3 years of follow-up: E/e´+e´, LV GLS, left atrial volume index (all P<0.01). In the multivariable model (C-index=0.65), only abnormal LV GLS was independently associated with all-cause mortality (HR, 1.35 [95% CI, 1.11-1.63]; P=0.002). Among patients with LVEF>55%, 498/1255 (40%) demonstrated abnormal LV GLS. Regardless of specific LVEF, patients with abnormal LV GLS demonstrated a higher burden of multiple comorbidities and higher event rates compared with patients with normal LV GLS.
Conclusions:
In a large, real-world HF with mildly reduced or preserved LVEF population, echocardiographic features, led by LV GLS, were associated with adverse outcomes irrespective of LVEF. A large proportion of patients demonstrate adverse myocardial function by LV GLS despite preserved LVEF and may represent a key cohort of interest for HF medical therapies and future clinical studies.
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