Incremental Prognostic Value of Regional Myocardial Flow Reserve Beyond Global Flow and Perfusion: REFINE PET
Abstract
Background: The incremental prognostic value of regional myocardial flow reserve (MFR) assessed by positron emission tomography (PET) myocardial perfusion imaging (MPI) beyond global MFR remains unclear. We sought to evaluate the prognostic value of regional MFR in the international multicenter REFINE PET registry.
Methods: This retrospective multicenter cohort study included 35,391 patients from 13 sites in the international REFINE PET registry who underwent rubidium-82 ( 82 Rb) and 13 N-ammonia ( 13 NH 3 ) PET MPI. Abnormal MFR was defined as <2.0. Patients were classified into three groups: MFR-Group 1 (normal global and regional MFR; n=19,744), MFR-Group 2 (normal global MFR but abnormal regional MFR; n=3,184), and MFR-Group 3 (abnormal global and regional MFR; n=12,463). Major adverse cardiovascular events (MACE) included all-cause mortality, non-fatal myocardial infarction, late revascularization (>90 days), and hospital admission for unstable angina.
Results: During a mean follow-up of 4.0 ± 2.9 years, 9,903 patients (28.0%) experienced MACE. Annualized MACE rates increased stepwise across MFR-Groups 1-3 (4.0%/year, 7.5%/year, and 11.8%/year, respectively; p <0.001). Abnormal regional MFR independently predicted MACE after adjustment for clinical risk factors, global MFR, and stress total perfusion deficit (HR 1.34, 95% CI 1.25–1.43). Adding regional MFR to a model including global MFR significantly improved model fit (χ² 4,784 to 4,871; p <0.001), discrimination (AUC 0.710 to 0.729; p <0.001), and reclassification (NRI 41.9%). Among patients with normal perfusion and preserved global MFR, abnormal regional MFR identified higher risk (5.0%/year vs. 2.8%/year; p <0.001).
Conclusions: Regional MFR provided incremental prognostic value beyond conventional PET MPI findings, including global MFR, and may refine risk stratification, particularly when global MFR is preserved.
Clinical perspectives: Global myocardial flow reserve (MFR) is widely used for risk stratification in patients undergoing positron emission tomography (PET) myocardial perfusion imaging (MPI). However, regional abnormalities in MFR may be overlooked when global MFR is preserved. In this international multicenter study of 35,391 patients, abnormal regional MFR was independently associated with major adverse cardiovascular events and provided incremental prognostic value beyond conventional clinical and PET-MPI findings, including global MFR and myocardial perfusion abnormalities. Importantly, even among patients with normal perfusion and preserved global MFR, those with abnormal regional MFR had a substantially higher annualized event rate than those with normal regional MFR (5.0% versus 2.8%). These findings highlight the importance of assessing regional MFR in addition to global MFR during routine PET-MPI interpretation.
Graphic Abstract:
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BibTeX
@misc{fujito2026incremental,
title = {{Incremental Prognostic Value of Regional Myocardial Flow Reserve Beyond Global Flow and Perfusion: REFINE PET}},
author = {Hidesato Fujito and Donghee Han and Alan Rozanski and Gloria J. Hong and Giselle Ramirez and Joanna X. Liang and Mark Lemley and Aakash Shanbhag and Robert J.H. Miller and Paul B. Kavanagh and Heidi Gransar and Leandro Slipczuk and Mark I. Travin and Erick Alexanderson and Isabel Carvajal-Juarez and Rene R.S. Packard and Mouaz Al-Mallah and Andrew J. Einstein and Attila Feher and Wanda Acampa and Stacey Knight and Viet T. Le and Steve Mason and Panithaya Chareonthaitawee and Ronny R. Buechel and Thomas L. Rosamond and Robert A. deKemp and Damini Dey and Marcelo F. Di Carli and Daniel S. Berman and Piotr J. Slomka},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.26366834},
url = {https://www.medrxiv.org/content/10.64898/2026.10.29.26366834v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Incremental Prognostic Value of Regional Myocardial Flow Reserve Beyond Global Flow and Perfusion: REFINE PET
AU - Hidesato Fujito
AU - Donghee Han
AU - Alan Rozanski
AU - Gloria J. Hong
AU - Giselle Ramirez
AU - Joanna X. Liang
AU - Mark Lemley
AU - Aakash Shanbhag
AU - Robert J.H. Miller
AU - Paul B. Kavanagh
AU - Heidi Gransar
AU - Leandro Slipczuk
AU - Mark I. Travin
AU - Erick Alexanderson
AU - Isabel Carvajal-Juarez
AU - Rene R.S. Packard
AU - Mouaz Al-Mallah
AU - Andrew J. Einstein
AU - Attila Feher
AU - Wanda Acampa
AU - Stacey Knight
AU - Viet T. Le
AU - Steve Mason
AU - Panithaya Chareonthaitawee
AU - Ronny R. Buechel
AU - Thomas L. Rosamond
AU - Robert A. deKemp
AU - Damini Dey
AU - Marcelo F. Di Carli
AU - Daniel S. Berman
AU - Piotr J. Slomka
PY - 2026
DA - 2026/10/29
PB - medRxiv
DO - 10.64898/2026.10.29.26366834
UR - https://www.medrxiv.org/content/10.64898/2026.10.29.26366834v1
AB - Background: The incremental prognostic value of regional myocardial flow reserve (MFR) assessed by positron emission tomography (PET) myocardial perfusion imaging (MPI) beyond global MFR remains unclear. We sought to evaluate the prognostic value of regional MFR in the international multicenter REFINE PET registry. Methods: This retrospective multicenter cohort study included 35,391 patients from 13 sites in the international REFINE PET registry who underwent rubidium-82 ( 82 Rb) and 13 N-ammonia ( 13 NH 3 ) PET MPI. Abnormal MFR was defined as <2.0. Patients were classified into three groups: MFR-Group 1 (normal global and regional MFR; n=19,744), MFR-Group 2 (normal global MFR but abnormal regional MFR; n=3,184), and MFR-Group 3 (abnormal global and regional MFR; n=12,463). Major adverse cardiovascular events (MACE) included all-cause mortality, non-fatal myocardial infarction, late revascularization (>90 days), and hospital admission for unstable angina. Results: During a mean follow-up of 4.0 ± 2.9 years, 9,903 patients (28.0%) experienced MACE. Annualized MACE rates increased stepwise across MFR-Groups 1-3 (4.0%/year, 7.5%/year, and 11.8%/year, respectively; p <0.001). Abnormal regional MFR independently predicted MACE after adjustment for clinical risk factors, global MFR, and stress total perfusion deficit (HR 1.34, 95% CI 1.25–1.43). Adding regional MFR to a model including global MFR significantly improved model fit (χ² 4,784 to 4,871; p <0.001), discrimination (AUC 0.710 to 0.729; p <0.001), and reclassification (NRI 41.9%). Among patients with normal perfusion and preserved global MFR, abnormal regional MFR identified higher risk (5.0%/year vs. 2.8%/year; p <0.001). Conclusions: Regional MFR provided incremental prognostic value beyond conventional PET MPI findings, including global MFR, and may refine risk stratification, particularly when global MFR is preserved. Clinical perspectives: Global myocardial flow reserve (MFR) is widely used for risk stratification in patients undergoing positron emission tomography (PET) myocardial perfusion imaging (MPI). However, regional abnormalities in MFR may be overlooked when global MFR is preserved. In this international multicenter study of 35,391 patients, abnormal regional MFR was independently associated with major adverse cardiovascular events and provided incremental prognostic value beyond conventional clinical and PET-MPI findings, including global MFR and myocardial perfusion abnormalities. Importantly, even among patients with normal perfusion and preserved global MFR, those with abnormal regional MFR had a substantially higher annualized event rate than those with normal regional MFR (5.0% versus 2.8%). These findings highlight the importance of assessing regional MFR in addition to global MFR during routine PET-MPI interpretation. Graphic Abstract:
ER -