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Predicting Sudden Cardiac Death in Heart Failure with Mildly Reduced/Preserved Left Ventricular Ejection Fraction: A

Mauro Feola1, Federico Landra1, Cosimo Angelo Greco2

  • 1Cardiology Division, Regina Montis Regalis Hospital, Azienda Sanitaria Locale Cuneo 1 (ASLCN1), 12084 Mondovì, Italy.

Journal of Clinical Medicine
|May 4, 2026
PubMed

Insights

Sudden cardiac death (SCD) risk in heart failure with preserved ejection fraction (HFpEF) is not well understood. While some drugs show no benefit, dapagliflozin may reduce SCD in HFpEF patients with prior reduced ejection fraction.

Area of Science:

  • Cardiology
  • Electrophysiology
  • Pharmacology

Background:

  • Sudden cardiac death (SCD) accounts for a significant portion of mortality in heart failure (HF), particularly in heart failure with reduced ejection fraction (HFrEF).
  • Data on SCD risk and ventricular arrhythmias in patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) are limited.
  • The incidence of investigator-reported ventricular tachycardia (VT) and ventricular fibrillation (VF) is 0.3% per person/year, suggesting an annual SCD rate of approximately 1.3% in the studied population.

Purpose of the Study:

  • To investigate the risk factors and incidence of SCD in patients with HFpEF.
  • To evaluate the effectiveness of specific medications (gliflozins, finerenone) in preventing SCD in HFpEF.
  • To explore novel methods for predicting SCD in HFpEF patients.

Main Methods:

  • Analysis of patient data to identify risk factors for SCD, including age, gender, diabetes, myocardial infarction history, left bundle branch block (LBBB), and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels.
  • Clinical trials comparing the incidence of SCD in HFpEF patients treated with gliflozins and finerenone versus placebo.
  • Assessment of SCD rates in patients with heart failure with improved ejection fraction (HFimpEF) treated with dapagliflozin.

Main Results:

  • A subgroup of HFpEF patients characterized by specific clinical and biomarker profiles exhibited a higher 5-year cumulative incidence of sudden death (SD) of 11%.
  • Neither gliflozins nor finerenone demonstrated a significant reduction in SCD incidence compared to placebo in HFpEF patients.
  • Dapagliflozin use was associated with a significantly lower rate of SCD in HFimpEF patients (those with prior LVEF < 40%).

Conclusions:

  • Arrhythmic SCD in HFpEF may be more frequently driven by bradyarrhythmia than VT/VF.
  • Current drug therapies have not yet demonstrated a clear benefit in preventing SCD in the HFpEF population.
  • Emerging techniques like cardiac magnetic resonance, myocardial scintigraphy, genetic assessment, and electrophysiologic studies show promise for SCD prediction in HFpEF.

Keywords:
heart failurepreserved left ventricular ejection fractionsudden cardiac death

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