Long-term Prognostic Value of Stress Phase Entropy for Predicting Major Cardiac Events in Patients with Known or Suspected Coronary Artery Disease

Q: What are the key findings of this study?

Higher stress phase entropy was independently associated with an increased risk of major cardiac events (HR 1.021) and significantly improved long-term risk stratification in patients with stable CAD.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Known or suspected coronary artery disease (CAD) (n=2258). Intervention: Stress phase entropy vs. Lower stress phase entropy. Primary outcome: Major cardiac events (MCEs) including cardiac death, nonfatal myocardial infarction, and severe heart failure requiring hospitalization (HR 1.021, 95% CI 1.007-1.035, p=0.0028).

Q: What does this research mean for the field?

Higher stress phase entropy derived from ECG-gated SPECT myocardial perfusion imaging is an independent predictor of major cardiac events and improves risk stratification beyond conventional perfusion and left ventricular ejection fraction assessments. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Katsunori Fukumoto; Shunichi Yoda; Yudai Tanaka; Tokio Nishiwaki; Takumi Hatta; Yasuyuki Suzuki; Naoya Matsumoto; Yasuo Okumura

doi:10.2169/internalmedicine.7881-26

January 1, 2026Internal MedicineOpen Access

Long-term Prognostic Value of Stress Phase Entropy for Predicting Major Cardiac Events in Patients with Known or Suspected Coronary Artery Disease

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Key result

Higher stress phase entropy linked to ~2% higher risk of major cardiac events in stable CAD.

HR 1.021
95% CI 1.007-1.035
P=0.0028
n=2,258

Why the study?

The prognostic value of stress phase entropy derived from ECG-gated SPECT MPI for predicting major cardiac events in patients with known or suspected CAD was not well established.

Key Points

To evaluate the long-term prognostic value of stress phase entropy derived from ECG-gated SPECT myocardial perfusion imaging for predicting major cardiac events in patients with known or suspected coronary artery disease.
Followed 2,258 Japanese patients with known or suspected coronary artery disease who underwent Tc-tetrofosmin ECG-gated SPECT myocardial perfusion imaging.
Assessed left ventricular dyssynchrony using stress phase entropy alongside phase standard deviation and bandwidth.
Evaluated predictors of major cardiac events—defined as cardiovascular death, non-fatal myocardial infarction, and severe heart failure hospitalization—using Cox proportional hazards regression and Kaplan-Meier analyses.
Major cardiac events occurred in 293 of 2,258 patients (13.0%), with incidence rising significantly across stress phase entropy tertiles from 6.4% (48/753) to 9.3% (70/752) and 23.2% (175/753) (P < 0.001).
Multivariate Cox analysis identified stress phase entropy as an independent predictor of major cardiac events (HR 1.021, 95% CI 1.007–1.035, P = 0.0028), along with age (HR 1.062, 95% CI 1.049–1.076), eGFR (HR 0.984, 95% CI 0.978–0.989), SDS (HR 1.034, 95% CI 1.006–1.062), and stress LVEF (HR 0.963, 95% CI 0.952–0.975).
Adding stress phase entropy to models with summed stress score and stress LVEF significantly increased the global chi-squared value (P < 0.01), whereas adding phase standard deviation or bandwidth did not.

Study Design

Type

Cohort (n=2,258)

Multicenter

No

Structured PICO

P

Population

2,258 Japanese patients with known or suspected coronary artery disease who underwent rest and stress ECG-gated SPECT MPI, followed for an average of 6 years.

E

Exposure

Assessment of stress phase entropy (a left ventricular mechanical dyssynchrony index derived from phase analysis of ECG-gated SPECT MPI).

O

Outcome

Composite of major cardiac events (MCEs), including cardiac death, nonfatal myocardial infarction (MI), and severe heart failure requiring hospitalization over a 6-year follow-up.composite

Main Result

Hazard Ratio: 1.021 (95% CI 1.007–1.035)

p-value: p=0.0028

Limitations

Retrospective analysis of a single-center study, limiting generalizability to other populations.
Potential institutional bias in the optimal medical treatment used to prevent MCEs.
Did not evaluate the optimization of medical therapy or chronic-phase therapeutic interventions during the follow-up period.
LV mechanical dyssynchrony was assessed using stress scans only; resting phase variables were not analyzed.
Use of a low-dose tracer (201Tl) which might increase variability compared to high-dose tracers.
Retrospective design
Single-center study
Only stress images were used for the analysis of ECG-gated SPECT MPI

Implication

Stress phase entropy derived from ECG-gated SPECT MPI is a strong, independent predictor of major cardiac events, offering improved long-term risk stratification in CAD patients beyond traditional perfusion and LVEF assessment.

Abstract

Tc-tetrofosmin electrocardiogram-gated (ECG)-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI).Results During the follow-up, 293 patients (13%) experienced MCEs. A multivariate analysis showed that age, the summed difference score, estimated glomerular filtration rate, stress LV ejection fraction (EF), and stress entropy were independent predictors of MCEs. A Kaplan-Meier analysis showed significant risk stratification between each group in the stress phase entropy tertiles. The global chi-squared value predicting MCE onset was significantly improved in the model with the summed stress score and stress LVEF plus entropy, but it was comparable in the model with added bandwidth or phase SD.Conclusion Stress phase entropy derived from ECG-gated SPECT MPI was a strong long-term predictor of MCEs in Japanese patients with CAD (known or suspected) and it is considered to be the most useful left ventricular dyssynchrony index to improve risk stratification over prediction by perfusion and LVEF assessment alone.

Discussion

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Cite This Study

Fukumoto et al. (2026) conducted a cohort in Known or suspected coronary artery disease (CAD) (n=2,258). Stress phase entropy vs. Lower stress phase entropy was evaluated on Major cardiac events (MCEs) including cardiac death, nonfatal myocardial infarction, and severe heart failure requiring hospitalization (HR 1.021, 95% CI 1.007-1.035, p=0.0028). Higher stress phase entropy was independently associated with an increased risk of major cardiac events (HR 1.021) and significantly improved long-term risk stratification in patients with stable CAD.

synapsesocial.com/papers/6ad0fd1915427f6a840404eb https://doi.org/10.2169/internalmedicine.7881-26

Topics

Coronary artery disease

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Long-term Prognostic Value of Stress Phase Entropy for Predicting Major Cardiac Events in Patients with Known or Suspected Coronary Artery Disease

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Topics

Long-term Prognostic Value of Stress Phase Entropy for Predicting Major Cardiac Events in Patients with Known or Suspected Coronary Artery Disease

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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