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Peer-reviewedCC BY-NC-NDJACC. Advances

Electrophysiologic Phenotype Outperforms Left Ventricular Ejection Fraction for Mortality Prediction in Immune Checkpoint Inhibitor Myocarditis.

  • Bakr Alhayek1
  • Mohamed Ibrahim2
  • Munir Ghandour3
  • Diya Asad1
  • Muhammad Umar1
  • Rebekah Alison1
  • Asha Ramsakal1
  • J Christopher Ray4
  • Taimur Sher5
  • Grace Lin4
  • Awais Malik6
6 affiliations
  1. 1Department of Internal Medicine, AdventHealth Tampa, Tampa, Florida, USA.
  2. 2Department of Internal Medicine, Mayo Clinic, Jacksonville, Florida, USA. Electronic address: https://twitter.com/MohamedIbr3463.
  3. 3Older People and Stroke Services, Glasgow Royal Infirmary, Glasgow, Scotland, United Kingdom.
  4. 4Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, Florida, USA.
  5. 5Department of Hematology and Oncology, Mayo Clinic, Jacksonville, Florida, USA.
  6. 6Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, Florida, USA. Electronic address: [email protected].
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Abstract

Background

Immune checkpoint inhibitor (ICI)-associated myocarditis carries mortality rates approaching 50%. Risk stratification relies heavily on left ventricular ejection fraction (LVEF), yet many fatal cases occur despite preserved systolic function.Objectives

The study aims to compare the prognostic value of electrophysiologic involvement vs LVEF in ICI-associated myocarditis.Methods

We systematically searched PubMed for ICI-associated myocarditis cases with extractable patient-level data. Electrophysiologic phenotype (EP) was defined by clinically significant conduction disease or ventricular arrhythmia, including high-grade atrioventricular block, ventricular tachycardia, ventricular fibrillation, or cardiac arrest. LVEF was dichotomized at ≤35%. Cluster-robust logistic regression was used to assess associations with mortality.Results

From 242 publications, 319 cases were extracted; 180 with complete data comprised the analytical cohort (77 deaths; 42.8% mortality). EP involvement (66.7% of cases) was associated with significantly higher mortality vs EP-negative cases (55.0% vs 18.3%; risk ratio: 3.00; 95% CI: 1.72-5.24; P < 0.001). LVEF ≤35% was not significantly associated with mortality (50.7% vs 38.1%; P = 0.125). Among patients with an LVEF >35%, EP involvement was associated with markedly higher mortality (55.1% vs 11.4%; P < 0.001). In adjusted models, EP remained associated with mortality on both the odds-ratio scale (OR: 5.27; 95% CI: 2.29-12.13; P < 0.001) and risk-ratio scale (RR: 2.94; 95% CI: 1.54-5.59; P < 0.001), whereas LVEF ≤35% was not independently associated with mortality.Conclusions

Electrophysiologic involvement is a dominant prognostic marker in ICI-associated myocarditis, particularly for risk stratification among patients with an LVEF >35%. Risk stratification should prioritize cardiac rhythm monitoring and identification of conduction abnormalities over reliance on LVEF alone.

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Cite

BibTeXRIS
BibTeX
@article{alhayek2026electrophysiologic,
  title = {{Electrophysiologic Phenotype Outperforms Left Ventricular Ejection Fraction for Mortality Prediction in Immune Checkpoint Inhibitor Myocarditis.}},
  author = {Bakr Alhayek and Mohamed Ibrahim and Munir Ghandour and Diya Asad and Muhammad Umar and Rebekah Alison and Asha Ramsakal and J Christopher Ray and Taimur Sher and Grace Lin and Awais Malik},
  journal = {JACC. Advances},
  year = {2026},
  month = oct,
  doi = {10.1016/j.jacadv.2026.103337},
  url = {https://europepmc.org/article/MED/42868965},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Electrophysiologic Phenotype Outperforms Left Ventricular Ejection Fraction for Mortality Prediction in Immune Checkpoint Inhibitor Myocarditis.
AU  - Bakr Alhayek
AU  - Mohamed Ibrahim
AU  - Munir Ghandour
AU  - Diya Asad
AU  - Muhammad Umar
AU  - Rebekah Alison
AU  - Asha Ramsakal
AU  - J Christopher Ray
AU  - Taimur Sher
AU  - Grace Lin
AU  - Awais Malik
PY  - 2026
DA  - 2026/10/13
JO  - JACC. Advances
DO  - 10.1016/j.jacadv.2026.103337
UR  - https://europepmc.org/article/MED/42868965
AB  - Background  Immune checkpoint inhibitor (ICI)-associated myocarditis carries mortality rates approaching 50%. Risk stratification relies heavily on left ventricular ejection fraction (LVEF), yet many fatal cases occur despite preserved systolic function.Objectives  The study aims to compare the prognostic value of electrophysiologic involvement vs LVEF in ICI-associated myocarditis.Methods  We systematically searched PubMed for ICI-associated myocarditis cases with extractable patient-level data. Electrophysiologic phenotype (EP) was defined by clinically significant conduction disease or ventricular arrhythmia, including high-grade atrioventricular block, ventricular tachycardia, ventricular fibrillation, or cardiac arrest. LVEF was dichotomized at ≤35%. Cluster-robust logistic regression was used to assess associations with mortality.Results  From 242 publications, 319 cases were extracted; 180 with complete data comprised the analytical cohort (77 deaths; 42.8% mortality). EP involvement (66.7% of cases) was associated with significantly higher mortality vs EP-negative cases (55.0% vs 18.3%; risk ratio: 3.00; 95% CI: 1.72-5.24; P < 0.001). LVEF ≤35% was not significantly associated with mortality (50.7% vs 38.1%; P = 0.125). Among patients with an LVEF >35%, EP involvement was associated with markedly higher mortality (55.1% vs 11.4%; P < 0.001). In adjusted models, EP remained associated with mortality on both the odds-ratio scale (OR: 5.27; 95% CI: 2.29-12.13; P < 0.001) and risk-ratio scale (RR: 2.94; 95% CI: 1.54-5.59; P < 0.001), whereas LVEF ≤35% was not independently associated with mortality.Conclusions  Electrophysiologic involvement is a dominant prognostic marker in ICI-associated myocarditis, particularly for risk stratification among patients with an LVEF >35%. Risk stratification should prioritize cardiac rhythm monitoring and identification of conduction abnormalities over reliance on LVEF alone.
SN  - 2772-963X
ER  -