Ascending Aortic Calcium Identifies Patients at Risk Despite Normal Myocardial Flow, Perfusion and Coronary Calcium: A 13-Site Cohort Study

  1. Clemens P. Spielvogel
  2. Aakash Shanbhag
  3. Shaun Khanna
  4. Tara Zuhair Kassem
  5. Mark Lemley
  6. Jirong Yi
  7. Giselle Ramirez
  8. Paul Kavanagh
  9. Assiata Kamagate
  10. Leandro Slipczuk
  11. Mark I. Travin
  12. Ronny R. Buechel
  13. Robert A. DeKemp
  14. Erick Alexanderson
  15. Isabel Carvajal-Juarez
  16. René R.S. Packard
  17. Mouaz Al-Mallah
  18. Andrew J. Einstein
  19. Wanda Acampa
  20. Stacey Knight
  21. Viet T. Le
  22. Steve Mason
  23. Thomas L. Rosamond
  24. Robert J.H. Miller
  25. Panithaya Chareonthaitawee
  26. Damini Dey
  27. Daniel S. Berman
  28. Marcelo F. Di Carli
  29. Piotr J. Slomka
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Abstract

Background

Patients with normal perfusion, normal myocardial flow reserve (MFR) and no coronary artery calcium (CAC) on myocardial perfusion imaging are considered low risk. Yet, adverse events still occur and no routinely reported imaging marker stratifies residual risk. This study aims to determine whether fully automated ascending aortic calcification (AAC) from the attenuation correction CT stratifies risk in these patients.

Methods

In the multicenter REFINE-PET registry, AAC was quantified from non-contrast CT using deep learning aortic segmentation and Agatston scoring. Triple-normal was defined as stress total perfusion deficit (TPD) <5%, MFR >2 and CAC 0. The primary endpoint was cardiovascular death, myocardial infarction or heart failure admission, with heart failure admission as key secondary endpoint. Cox models were adjusted for clinical confounders.

Results

Of 21,923 patients, 3,580 (16.3%) were triple-normal, of whom 1,322 (36.9%) had AAC (median Agatston 65, IQR 22-212). Agreement with three blinded readers was good to excellent (Intraclass correlation coefficient 0.87-0.90). Over a median follow-up of 52 months (IQR 26-69), 194 primary events occurred. Per standard deviation, AAC was independently associated with the primary endpoint (adjusted HR 1.24, 95% CI 1.09-1.40; p<0.001), heart failure admission (adjusted HR 1.30, 95% CI 1.10-1.55; p=0.003) and all-cause mortality (adjusted HR 1.17, 95% CI 1.04-1.32; p=0.009). AAC improved model fit beyond clinical factors, MFR and TPD (p≤0.009), with modest gains in discrimination (ΔC 0.007-0.009).

Conclusions

In patients with normal PET readouts, automated AAC was independently associated with adverse outcomes, most strongly heart failure admission, beyond clinical risk factors, perfusion and flow.

Clinical Perspective

What Is New?

  • In 3,580 patients with normal perfusion, normal myocardial flow reserve and no coronary artery calcium on PET, more than one in three had ascending aortic calcification on the attenuation correction CT.

  • Ascending aortic calcification was independently associated with cardiovascular death, myocardial infarction or heart failure admission (adjusted hazard ratio per SD 1.24, 95% CI 1.09-1.40), most strongly with heart failure admission.

  • A fast, fully automated method scored ascending aortic calcification with agreement to expert readers similar to agreement between readers.

What Are the Clinical Implications?

  • A normal perfusion PET with normal flow and no coronary calcium does not mean uniformly low risk when the ascending aorta is calcified.

  • Because ascending aortic calcification is scored automatically from the CT acquired with every perfusion PET, it could be reported routinely without additional scanning, cost or radiation.

  • Patients presumed low risk who have ascending aortic calcification may warrant heart failure-oriented prevention, such as natriuretic peptide screening, pending prospective validation.

Article activity feed

  1. Version published to 10.64898/2026.10.09.26365170 on medRxiv