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Additive prognostic value of functional performance to coronary artery anatomy: the ISCHEMIA trial.

Publication ,  Journal Article
Ben Zekry, S; Tzimas, G; Leipsic, J; Broderick, S; Mancini, GBJ; Hague, CJ; Budoff, MJ; Min, JK; Chaitman, BR; Rockhold, FW; Cyr, D; Shaw, LJ ...
Published in: Eur Heart J Cardiovasc Imaging
April 30, 2026

AIMS: To assess whether baseline functional performance assessed by exercise treadmill stress testing (EST) has additive value to coronary computed tomography angiography (CCTA) for risk stratification among patients with chronic coronary disease (CCD) and moderate or severe ischaemia. METHODS AND RESULTS: We performed a subgroup analysis of the ISCHEMIA trial including participants who underwent EST and CCTA. EST data and severity of coronary artery disease (CAD) on CCTA were evaluated by core laboratories, blinded to clinical data and results of the other tests. The primary outcome for this analysis was all-cause death. Secondary outcomes were cardiovascular death, cardiovascular death or myocardial infarction (MI), MI and a composite of cardiovascular death, MI, or hospitalization for heart failure, unstable angina, or resuscitated cardiac arrest. EST and the number of vessels diseased on CCTA were both interpretable in 1864 patients (median age 62 years, IQR 55-68, 83% males). During a median follow-up of 3.1 years, 69 patients died. Higher peak metabolic equivalents (METs) achieved on the qualifying stress test was associated with lower all-cause death (HR 0.86, 95% CI 0.76-0.98; P = 0.025). The addition of peak METs to CAD severity improved the predictive ability of the all-cause death and CV death models by 10-20% and 8-13% respectively, depending on the metrics used for CCTA. Adding peak METs to CCTA anatomical models resulted in better prediction of MI by 11-17%, cardiovascular death or MI by 10-14%, and 5-component composite outcome by 12-16%. CONCLUSION: Peak METs on EST, a marker of functional performance, added prognostic value to models including CCTA anatomical findings in patients with CCD and moderate or severe ischaemia.

Duke Scholars

Published In

Eur Heart J Cardiovasc Imaging

DOI

EISSN

2047-2412

Publication Date

April 30, 2026

Volume

27

Issue

5

Start / End Page

952 / 966

Location

England

Related Subject Headings

  • Severity of Illness Index
  • Risk Assessment
  • Prognosis
  • Predictive Value of Tests
  • Myocardial Ischemia
  • Middle Aged
  • Male
  • Humans
  • Female
  • Exercise Test
 

Citation

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Ben Zekry, S., Tzimas, G., Leipsic, J., Broderick, S., Mancini, G. B. J., Hague, C. J., … Reynolds, H. R. (2026). Additive prognostic value of functional performance to coronary artery anatomy: the ISCHEMIA trial. Eur Heart J Cardiovasc Imaging, 27(5), 952–966. https://doi.org/10.1093/ehjci/jeag032
Ben Zekry, Sagit, Georgios Tzimas, Jonathon Leipsic, Samuel Broderick, GB John Mancini, Cameron J. Hague, Matthew J. Budoff, et al. “Additive prognostic value of functional performance to coronary artery anatomy: the ISCHEMIA trial.Eur Heart J Cardiovasc Imaging 27, no. 5 (April 30, 2026): 952–66. https://doi.org/10.1093/ehjci/jeag032.
Ben Zekry S, Tzimas G, Leipsic J, Broderick S, Mancini GBJ, Hague CJ, et al. Additive prognostic value of functional performance to coronary artery anatomy: the ISCHEMIA trial. Eur Heart J Cardiovasc Imaging. 2026 Apr 30;27(5):952–66.
Ben Zekry, Sagit, et al. “Additive prognostic value of functional performance to coronary artery anatomy: the ISCHEMIA trial.Eur Heart J Cardiovasc Imaging, vol. 27, no. 5, Apr. 2026, pp. 952–66. Pubmed, doi:10.1093/ehjci/jeag032.
Ben Zekry S, Tzimas G, Leipsic J, Broderick S, Mancini GBJ, Hague CJ, Budoff MJ, Min JK, Chaitman BR, Rockhold FW, Cyr D, Shaw LJ, Berman DS, Picard MH, Mark DB, Fleg JL, Poh KK, Ali ZA, Stone GW, O’Brien SM, Hochman JS, Maron DJ, Reynolds HR. Additive prognostic value of functional performance to coronary artery anatomy: the ISCHEMIA trial. Eur Heart J Cardiovasc Imaging. 2026 Apr 30;27(5):952–966.
Journal cover image

Published In

Eur Heart J Cardiovasc Imaging

DOI

EISSN

2047-2412

Publication Date

April 30, 2026

Volume

27

Issue

5

Start / End Page

952 / 966

Location

England

Related Subject Headings

  • Severity of Illness Index
  • Risk Assessment
  • Prognosis
  • Predictive Value of Tests
  • Myocardial Ischemia
  • Middle Aged
  • Male
  • Humans
  • Female
  • Exercise Test