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Interaction of impaired myocardial flow reserve and extent of myocardial ischemia assessed using 13N-ammonia positron emission tomography imaging on adverse cardiovascular outcomes

  • ORIGINAL ARTICLE
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Journal of Nuclear Cardiology Aims and scope

Abstract

Background

Myocardial flow reserve (MFR) and the extent of myocardial ischemia identify patients at high risk of major adverse cardiovascular events (MACEs). Associations between positron emission tomography (PET)-assessed extent of ischemia, MFR, and MACEs is unclear.

Method

Overall, 640 consecutive patients with suspected or known coronary artery disease undergoing 13N-ammonia myocardial perfusion PET were followed-up for MACEs. Patients were categorized into three groups based on myocardial ischemia severity: Group I (n = 335), minimal (myocardial ischemia < 5%); Group II (n = 150), mild (5–10%); and Group III (n = 155), moderate-to-severe (> 10%).

Results

Cardiovascular death and MACEs occurred in 17 (3%) and 93 (15%) patients, respectively. Following statistical adjustment for confounding factors, impaired MFR (global MFR < 2.0) was revealed as an independent predictor of MACEs in Groups I (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.48–5.64; P = 0.002) and II (HR, 3.40; 95% CI 1.37–8.41; P = 0.008) but was not significant in Group III (HR, 1.15; 95% CI 0.59–2.26; P = 0.67), with a significant interaction (P < 0.0001) between the extent of myocardial ischemia and MFR.

Conclusion

Impaired MFR was significantly associated with increased risk of MACEs in patients with ≤ 10% myocardial ischemia but not with those having > 10% ischemia, allowing a clinically effective risk stratification.

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Abbreviations

CAD:

Coronary artery disease

HF:

Heart failure

MACE:

Major adverse cardiac event

MBF:

Myocardial blood flow

MFR:

Myocardial flow reserve

MPI:

Myocardial perfusion imaging

PCI:

Percutaneous coronary intervention

PET:

Positron emission tomography

SDS:

Summed difference score

References

  1. Hachamovitch R, Hayes SW, Friedman JD, Cohen I, Berman DS. Comparison of the short-term survival benefit associated with revascularization compared with medical therapy in patients with no prior coronary artery disease undergoing stress myocardial perfusion single photon emission computed tomography. Circulation 2003;107:2900‐7.

    Article  PubMed  Google Scholar 

  2. Hachamovitch R, Rozanski A, Shaw LJ, Stone GW, Thomson LE, Friedman JD. Impact of ischaemia and scar on the therapeutic benefit derived from myocardial revascularization vs. medical therapy among patients undergoing stress-rest myocardial perfusion scintigraphy. Eur Heart J 2011;32:1012‐24.

    Article  PubMed  Google Scholar 

  3. Dilsizian V, Bacharach SL, Beanlands RS, Bergmann SR, Delbeke D, Dorbala S, et al. ASNC imaging guidelines/SNMMI procedure standard for positron emission tomography (PET) nuclear cardiology procedures. J Nucl Cardiol 2016;23:1187‐226.

    Article  PubMed  Google Scholar 

  4. Patel KK, Spertus JA, Chan PS, Sperry BW, Thompson RC, Al Badarin F, et al. Extent of myocardial ischemia on positron emission tomography and survival benefit with early revascularization. J Am Coll Cardiol 2019;74:1645‐54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Yoshinaga K, Chow BJ, Williams K, Chen L, deKemp RA, Garrard L, et al. What is the prognostic value of myocardial perfusion imaging using rubidium-82 positron emission tomography? J Am Coll Cardiol 2006;48:1029‐39.

    Article  PubMed  Google Scholar 

  6. Herzog BA, Husmann L, Valenta I, Gaemperli O, Siegrist PT, Tay FM, et al. Long-term prognostic value of 13N-ammonia myocardial perfusion positron emission tomography added value of coronary flow reserve. J Am Coll Cardiol 2009;54:150‐6.

    Article  PubMed  Google Scholar 

  7. Green R, Cantoni V, Acampa W, Assante R, Zampella E, Nappi C, et al. Prognostic value of coronary flow reserve in patients with suspected or known coronary artery disease referred to PET myocardial perfusion imaging: A meta-analysis. J Nucl Cardiol 2021;28:904‐18.

    Article  PubMed  Google Scholar 

  8. Patel KK, Spertus JA, Chan PS, Sperry BW, Al Badarin F, Kennedy KF, et al. Myocardial blood flow reserve assessed by positron emission tomography myocardial perfusion imaging identifies patients with a survival benefit from early revascularization. Eur Heart J 2020;41:759‐68.

    Article  CAS  PubMed  Google Scholar 

  9. Taqueti VR, Hachamovitch R, Murthy VL, Naya M, Foster CR, Hainer J, et al. Global coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity and modifies the effect of early revascularization. Circulation 2015;131:19‐27.

    Article  PubMed  Google Scholar 

  10. Shaw LJ, Berman DS, Maron DJ, Mancini GB, Hayes SW, Hartigan PM, et al. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation 2008;117:1283‐91.

    Article  PubMed  Google Scholar 

  11. Assante R, Mainolfi CG, Zampella E, Gaudieri V, Nappi C, Mannarino T, et al. Relation between myocardial blood flow and cardiac events in diabetic patients with suspected coronary artery disease and normal myocardial perfusion imaging. J Nucl Cardiol 2021;28:1222‐33.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Naya M, Murthy VL, Foster CR, Gaber M, Klein J, Hainer J, et al. Prognostic interplay of coronary artery calcification and underlying vascular dysfunction in patients with suspected coronary artery disease. J Am Coll Cardiol 2013;61:2098‐106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Genders TS, Steyerberg EW, Hunink MG, Nieman K, Galema TW, Mollet NR, et al. Prediction model to estimate presence of coronary artery disease: retrospective pooled analysis of existing cohorts. BMJ 2012;344:e3485.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Rapsomaniki E, Shah A, Perel P, Denaxas S, George J, Nicholas O, et al. Prognostic models for stable coronary artery disease based on electronic health record cohort of 102 023 patients. Eur Heart J 2014;35:844‐52.

    Article  CAS  PubMed  Google Scholar 

  15. Slomka PJ, Alexanderson E, Jacome R, Jimenez M, Romero E, Meave A, et al. Comparison of clinical tools for measurements of regional stress and rest myocardial blood flow assessed with 13N-ammonia PET/CT. J Nucl Med 2012;53:171‐81.

    Article  CAS  PubMed  Google Scholar 

  16. Hutchins GD, Schwaiger M, Rosenspire KC, Krivokapich J, Schelbert H, Kuhl DE. Noninvasive quantification of regional blood flow in the human heart using N-13 ammonia and dynamic positron emission tomographic imaging. J Am Coll Cardiol 1990;15:1032‐42.

    Article  CAS  PubMed  Google Scholar 

  17. Petretta M, Acampa W, Daniele S, Zampella E, Assante R, Nappi C, et al. Long-term survival benefit of coronary revascularization in patients undergoing stress myocardial perfusion imaging. Circ J 2016;80:485‐93.

    Article  PubMed  Google Scholar 

  18. Farhad H, Dunet V, Bachelard K, Allenbach G, Kaufmann PA, Prior JO. Added prognostic value of myocardial blood flow quantitation in rubidium-82 positron emission tomography imaging. Eur Heart J Cardiovasc Imaging 2013;14:1203‐10.

    Article  PubMed  Google Scholar 

  19. Monroy-Gonzalez AG, Tio RA, de Groot JC, Boersma HH, Prakken NH, De Jongste MJL, et al. Long-term prognostic value of quantitative myocardial perfusion in patients with chest pain and normal coronary arteries. J Nucl Cardiol 2019;26:1844‐52.

    Article  PubMed  Google Scholar 

  20. Maron DJ, Hochman JS, Reynolds HR, Bangalore S, O’Brien SM, Boden WE, et al. Initial invasive or conservative strategy for stable coronary disease. N Engl J Med 2020;382:1395‐407.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Megna R, Petretta M, Assante R, Zampella E, Nappi C, Gaudieri V, et al. External validation of the CRAX2MACE model in an Italian cohort of patients with suspected coronary artery disease undergoing stress myocardial perfusion imaging. J Nucl Cardiol 2021 (in press).

  22. Nappi C, Petretta M, Assante R, Zampella E, Gaudieri V, Cantoni V, et al. Prognostic value of heart rate reserve in patients with suspected coronary artery disease undergoing stress myocardial perfusion imaging. J Nucl Cardiol 2022;29:2521‐30.

    Article  PubMed  Google Scholar 

  23. Lindholm D, Lindback J, Armstrong PW, Budaj A, Cannon CP, Granger CB, et al. Biomarker-based risk model to predict cardiovascular mortality in patients with stable coronary disease. J Am Coll Cardiol 2017;70:813‐26.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiology, Hokkaido Ohno Memorial Hospital, 2-1-16-1 Miyanosawa, Nishi-Ku, Sapporo, 063-0052, Japan

    Shiro Miura MD, MSc & Takehiro Yamashita MD, PhD

  2. Department of Radiology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan

    Atsutaka Okizaki MD, PhD

  3. Department of Healthcare Quality Assessment, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Hiraku Kumamaru MD, PhD

  4. Department of Radiology, Saitama Medical Center, Jichi Medical University, Saitama-Shi, Japan

    Osamu Manabe MD, PhD

  5. Department of Cardiovascular Medicine, Hokkaido, University Graduate School of Medicine, Sapporo, Japan

    Masanao Naya MD, PhD

  6. Department of Diagnostic Radiology, Hokkaido Ohno Memorial Hospital, Sapporo, Japan

    Chihoko Miyazaki MD, PhD

Authors
  1. Shiro Miura MD, MSc
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  2. Atsutaka Okizaki MD, PhD
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  3. Hiraku Kumamaru MD, PhD
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  4. Osamu Manabe MD, PhD
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  5. Masanao Naya MD, PhD
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  6. Chihoko Miyazaki MD, PhD
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  7. Takehiro Yamashita MD, PhD
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Correspondence to Shiro Miura MD, MSc.

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Miura, S., Okizaki, A., Kumamaru, H. et al. Interaction of impaired myocardial flow reserve and extent of myocardial ischemia assessed using 13N-ammonia positron emission tomography imaging on adverse cardiovascular outcomes. J. Nucl. Cardiol. 30, 2043–2053 (2023). https://doi.org/10.1007/s12350-023-03255-x

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