Ascending Aortic Calcium Identifies Patients at Risk Despite Normal Myocardial Flow, Perfusion and Coronary Calcium: A 13-Site Cohort Study
- 1Cedars-Sinai Medical Center
Abstract
BackgroundPatients 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.
MethodsIn 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.
ResultsOf 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 ({Delta}C 0.007-0.009).
ConclusionsIn 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 PerspectiveO_ST_ABSWhat Is New?C_ST_ABSO_LIIn 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. C_LIO_LIAscending 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. C_LIO_LIA fast, fully automated method scored ascending aortic calcification with agreement to expert readers similar to agreement between readers. C_LI
What Are the Clinical Implications?O_LIA normal perfusion PET with normal flow and no coronary calcium does not mean uniformly low risk when the ascending aorta is calcified. C_LIO_LIBecause 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. C_LIO_LIPatients presumed low risk who have ascending aortic calcification may warrant heart failure-oriented prevention, such as natriuretic peptide screening, pending prospective validation. C_LI
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BibTeX
@misc{spielvogel2026ascending,
title = {{Ascending Aortic Calcium Identifies Patients at Risk Despite Normal Myocardial Flow, Perfusion and Coronary Calcium: A 13-Site Cohort Study}},
author = {C. Spielvogel and A. Shanbhag and S. Khanna and T. Zuhair Kassem and M. Lemley and J. Yi and G. Ramirez and P. Kavanagh and A. Kamagate and L. Slipczuk and M. I. Travin and R. R. Buechel and R. A. DeKemp and E. Alexanderson and I. Carvajal-Juarez and R. R. Packard and M. Al-Mallah and A. J. Einstein and W. Acampa and S. Knight and V. T. Le and S. Mason and T. L. Rosamond and R. J. Miller and P. Chareonthaitawee and D. Dey and D. S. Berman and M. F. Di Carli and P. Slomka},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.09.26365170},
url = {https://www.medrxiv.org/content/10.64898/2026.10.09.26365170v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Ascending Aortic Calcium Identifies Patients at Risk Despite Normal Myocardial Flow, Perfusion and Coronary Calcium: A 13-Site Cohort Study
AU - C. Spielvogel
AU - A. Shanbhag
AU - S. Khanna
AU - T. Zuhair Kassem
AU - M. Lemley
AU - J. Yi
AU - G. Ramirez
AU - P. Kavanagh
AU - A. Kamagate
AU - L. Slipczuk
AU - M. I. Travin
AU - R. R. Buechel
AU - R. A. DeKemp
AU - E. Alexanderson
AU - I. Carvajal-Juarez
AU - R. R. Packard
AU - M. Al-Mallah
AU - A. J. Einstein
AU - W. Acampa
AU - S. Knight
AU - V. T. Le
AU - S. Mason
AU - T. L. Rosamond
AU - R. J. Miller
AU - P. Chareonthaitawee
AU - D. Dey
AU - D. S. Berman
AU - M. F. Di Carli
AU - P. Slomka
PY - 2026
DA - 2026/10/09
PB - medRxiv
DO - 10.64898/2026.10.09.26365170
UR - https://www.medrxiv.org/content/10.64898/2026.10.09.26365170v1
AB - BackgroundPatients 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. MethodsIn 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. ResultsOf 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 ({Delta}C 0.007-0.009). ConclusionsIn 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 PerspectiveO_ST_ABSWhat Is New?C_ST_ABSO_LIIn 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. C_LIO_LIAscending 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. C_LIO_LIA fast, fully automated method scored ascending aortic calcification with agreement to expert readers similar to agreement between readers. C_LI What Are the Clinical Implications?O_LIA normal perfusion PET with normal flow and no coronary calcium does not mean uniformly low risk when the ascending aorta is calcified. C_LIO_LIBecause 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. C_LIO_LIPatients presumed low risk who have ascending aortic calcification may warrant heart failure-oriented prevention, such as natriuretic peptide screening, pending prospective validation. C_LI
ER -