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18F-sodium fluoride positron emission tomography following coronary computed tomography angiography in predicting long-term coronary events: a 5-year follow-up study

  • ORIGINAL ARTICLE
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Journal of Nuclear Cardiology Aims and scope

Abstract

Purpose

The predictive value of 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) in combination with coronary computed tomography (CT) angiography (CCTA) for future coronary events has attracted interest. We evaluated the potential of 18F-NaF PET/CT following CCTA to predict major coronary events (MACE) during a 5-year follow-up period.

Methods

Forty patients with coronary atherosclerotic lesions detected on CCTA underwent 18F-NaF PET/CT examination. Each lesion was evaluated for luminal stenosis and high-risk plaque (HRP) with < 30 Hounsfield units and a > 1.1 remodeling index on CCTA. Focal 18F-NaF uptake in each lesion was quantified using the maximum tissue-to-background ratio (TBRmax), and the maximum TBRmax per patient (M-TBRmax) was determined. We followed MACE (cardiac death, acute coronary syndrome, and/or coronary revascularization > 6 months after 18F-NaF PET/CT) for 5 years.

Results

In total, 142 coronary lesions were analyzed. Eleven patients experienced any MACE. Patients with MACE showed a higher M-TBRmax than those without (1.40 ± .19 vs. 1.18 ± .18, P = .0011), and the optimal M-TBRmax cutoff to predict MACE was 1.29. Patients with M-TBRmax of ≥ 1.29 had a higher risk of MACE than those with lower values (P = .012, log-rank test), whereas patients with obstructive stenosis and those with HRP did not. Multivariate Cox proportional analysis adjusted for age, sex, coronary risk factors, and CCTA findings showed that M-TBRmax of ≥ 1.29 remained an independent predictor of 5-year MACE (hazard ratio, 5.4; 95% confidence interval, 1.1–25.4; P = .034).

Conclusion

18F-NaF PET/CT following CCTA provides useful strategies to predict 5-year MACE.

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Abbreviations

ACS:

Acute coronary syndrome

CAD:

Coronary artery disease

CCTA:

Coronary computed tomography angiography

CT:

Computed tomography

18F-NaF:

18F-sodium fluoride

HRP:

High-risk plaque

MACE:

Major coronary events

PET:

Positron emission tomography

M-TBRmax :

Maximum TBRmax per patient

TBRmax :

Maximum tissue-to-background ratio

References

  1. Derlin T, Tóth Z, Papp L, Wisotzki C, Apostolova I, Habermann CR. Correlation of inflammation assessed by 18F-FDG PET, active mineral deposition assessed by 18F-fluoride PET, and vascular calcification in atherosclerotic plaque: a dual tracer PET/CT study. J Nucl Med 2011;52:1020‐7.

    Article  PubMed  Google Scholar 

  2. Dweck MR, Chow MW, Joshi NV, Williams MC, Jones C, Fletcher AM, et al. Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology. J Am Coll Cardiol 2012;59:1539‐48.

    Article  CAS  PubMed  Google Scholar 

  3. Aikawa E, Nahrendorf M, Figueiredo JL, Swirski FK, Shtatland T, Kohler RH, et al. Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo. Circulation 2007;116:2841‐50.

    Article  CAS  PubMed  Google Scholar 

  4. New SE, Goettsch C, Aikawa M, Marchini JF, Shibasaki M, Yabusaki K, et al. Macrophage-derived matrix vesicles: an alternative novel mechanism for microcalcification in atherosclerotic plaques. Circ Res 2013;113:72‐7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kitagawa T, Nakano Y. Innovative atherosclerosis imaging using 18F-NaF PET/CT: its clinical potential. J Nucl Cardiol 2022;29:1724‐8.

    Article  PubMed  Google Scholar 

  6. Kitagawa T, Yamamoto H, Toshimitsu S, Sasaki K, Senoo A, Kubo Y, et al. 18F-sodium fluoride positron emission tomography for molecular imaging of coronary atherosclerosis based on computed tomography analysis. Atherosclerosis 2017;263:385‐92.

    Article  CAS  PubMed  Google Scholar 

  7. Kwiecinski J, Dey D, Cadet S, Lee SE, Tamarappoo B, Otaki Y, et al. Predictors of 18F-sodium fluoride uptake in patients with stable coronary artery disease and adverse plaque features on computed tomography angiography. Eur Heart J Cardiovasc Imaging 2020;21:58‐66.

    Article  PubMed  Google Scholar 

  8. Majeed K, Bellinge JW, Butcher SC, Alcock R, Spiro J, Playford D, et al. Coronary 18F-sodium fluoride PET detects high-risk plaque features on optical coherence tomography and CT-angiography in patients with acute coronary syndrome. Atherosclerosis 2021;219:142‐8.

    Article  Google Scholar 

  9. Kitagawa T, Yamamoto H, Nakamoto Y, Sasaki K, Toshimitsu S, Tatsugami F, et al. Predictive value of 18F-sodium fluoride positron emission tomography in detecting high-risk coronary artery disease in combination with computed tomography. J Am Heart Assoc 2018;7:e010224.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kwiecinski J, Tzolos E, Adamson PD, Cadet S, Moss AJ, Joshi N, et al. Coronary 18F-sodium fluoride uptake predicts outcomes in patients with coronary artery disease. J Am Coll Cardiol 2020;75:3061‐74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Raff GL, Abidov A, Achenbach S, Berman DS, Boxt LM, Budoff MJ, et al. SCCT guidelines for the interpretation and reporting of coronary computed tomographic angiography. J Cardiovasc Comput Tomogr 2009;3:122‐36.

    Article  PubMed  Google Scholar 

  12. Motoyama S, Kondo T, Sarai M, Sugiura A, Harigaya H, Sato T, et al. Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes. J Am Coll Cardiol 2007;50:319‐26.

    Article  PubMed  Google Scholar 

  13. Motoyama S, Sarai M, Harigaya H, Anno H, Inoue K, Hara T, et al. Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J Am Coll Cardiol 2009;54:49‐57.

    Article  PubMed  Google Scholar 

  14. Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, et al. ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction—2002: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). Circulation 2002;106:1893‐900.

    Article  PubMed  Google Scholar 

  15. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol 2012;60:1581‐98.

    Article  PubMed  Google Scholar 

  16. Budoff MJ, Shaw LJ, Liu ST, Weinstein SR, Mosler TP, Tseng PH, et al. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol 2007;49:1860‐70.

    Article  PubMed  Google Scholar 

  17. Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR, et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med 2008;358:1336‐45.

    Article  CAS  PubMed  Google Scholar 

  18. Ishiwata Y, Kaneta T, Nawata S, Hino-Shishikura A, Yoshida K, Inoue T. Quantification of temporal changes in calcium score in active atherosclerotic plaque in major vessels by 18F-sodium fluoride PET/CT. Eur J Nucl Med Mol Imaging 2017;44:1529‐37.

    Article  CAS  PubMed  Google Scholar 

  19. Li X, Heber D, Cal-Gonzalez J, Karanikas G, Mayerhoefer ME, Rasul S, et al. Association between osteogenesis and inflammation during the progression of calcified plaque evaluated by 18F-Fluoride and 18F-FDG. J Nucl Med 2017;58:968‐74.

    Article  PubMed  Google Scholar 

  20. Nakamoto Y, Kitagawa T, Sasaki K, Tatsugami F, Awai K, Hirokawa Y, et al. Clinical implications of 18F-sodium fluoride uptake in subclinical aortic valve calcification: its relation to coronary atherosclerosis and its predictive value. J Nucl Cardiol 2019;28:1522‐31.

    Article  PubMed  Google Scholar 

  21. Bellinge JW, Francis RJ, Lee SC, Phillips M, Rajwani A, Lewis JR, et al. 18F-sodium fluoride positron emission tomography activity predicts the development of new coronary artery calcifications. Arterioscler Thromb Vasc Biol 2021;41:534‐41.

    CAS  PubMed  Google Scholar 

  22. Doris MK, Meah MN, Moss AJ, Andrews JPM, Bing R, Gillen R, et al. Coronary 18F-fluoride uptake and progression of coronary artery calcification. Circ Cardiovasc Imaging 2020;13:e011438.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kwiecinski J, Tzolos E, Fletcher AJ, Nash J, Meah MN, Cadet S, et al. Bypass grafting and native coronary artery disease activity. JACC Cardiovasc Imaging 2022;15:875‐87.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lee JM, Bang JI, Koo BK, Hwang D, Park J, Zhang J, et al. Clinical relevance of 18F-sodium fluoride positron-emission tomography in noninvasive identification of high-risk plaque in patients with coronary artery disease. Circ Cardiovasc Imaging 2017;10:e006704.

    Article  PubMed  Google Scholar 

  25. Kwiecinski J, Tzolos E, Meah MN, Cadet S, Adamson PD, Grodecki K, et al. Machine learning with 18F-sodium fluoride PET and quantitative plaque analysis on CT angiography for the future risk of myocardial infarction. J Nucl Med 2022;63:158‐65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kitagawa T, Sasaki K, Fujii Y, Tatsugami F, Awai K, Hirokawa Y, et al. A longitudinal pilot study to assess temporal changes in coronary arterial 18F-sodium fluoride uptake. J Nucl Cardiol 2022 (in press).

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Acknowledgments

We acknowledge the help and support of the radiography and radiochemistry staffs of the Hiroshima Heiwa Clinic. We thank Angela Morben, DVM, ELS, from Edanz (https://jp.edanz.com/ac), for editing a draft of this manuscript.

Funding

This work was supported in part by the Mochida Memorial Foundation for Medical and Pharmaceutical Research, and a JSPS KAKENHI Grant-in-Aid for Scientific Research (Grant Number 21K08127).

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan

    Toshiro Kitagawa MD, PhD, Yuto Fujii MD, Yuki Ikegami MD & Yukiko Nakano MD, PhD

  2. Hiroshima Heiwa Clinic, Hiroshima, Japan

    Ko Sasaki RT & Yutaka Hirokawa MD, PhD

  3. Department of Diagnostic Radiology, Hiroshima University Hospital, Hiroshima, Japan

    Fuminari Tatsugami MD, PhD & Kazuo Awai MD, PhD

Authors
  1. Toshiro Kitagawa MD, PhD
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  7. Yutaka Hirokawa MD, PhD
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  8. Yukiko Nakano MD, PhD
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Correspondence to Toshiro Kitagawa MD, PhD.

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Toshiro Kitagawa, Ko Sasaki, Yuto Fujii, Yuki Ikegami, Fuminari Tatsugami, Kazuo Awai, Yutaka Hirokawa, and Yukiko Nakano report no relevant disclosures.

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12350_2023_3277_MOESM1_ESM.tif

Supplementary Figure Kaplan–Meier curves for 5-year MACE stratified according to CCS (A), and receiver operating characteristic curves of CCS and M-TBRmax for predicting MACE (B). CCS, coronary calcium score; other abbreviations as Figure 1 and 2. Supplementary file1 (TIF 2090 kb)

Supplementary file2 (PPTX 1725 kb)

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Kitagawa, T., Sasaki, K., Fujii, Y. et al. 18F-sodium fluoride positron emission tomography following coronary computed tomography angiography in predicting long-term coronary events: a 5-year follow-up study. J. Nucl. Cardiol. 30, 2365–2378 (2023). https://doi.org/10.1007/s12350-023-03277-5

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