Clinical significance of quantitative assessment of right ventricular glucose metabolism in patients with heart failure with reduced ejection fraction

  • Szu-Ying Tsai
  • Yen-Wen WuEmail author
  • Shan-Ying Wang
  • Yu-Chien Shiau
  • Kuan-Ming Chiu
  • Hao-Yuan Tsai
  • Chien-Lin Lee
  • Jung-Cheng Hsu
  • Chung-Ming Tu
  • Heng-Hsu Lin
  • Shan-Hui Huang
Original Article
Part of the following topical collections:
  1. Cardiology



Dynamic 18F-fluorodeoxyglucose (FDG) PET can be used to quantitatively assess the rate of myocardial glucose uptake (MRGlu). The aim of this study was to evaluate the clinical significance and prognostic value of right ventricular (RV) MRGlu in patients with coronary artery disease and heart failure with reduced ejection fraction.


Patients with left ventricular ejection fraction (LVEF) ≤ 40% were consecutively enrolled for FDG PET between November 2012 and May 2017. Global LV and RV MRGlu (μmol/min/100 g) were analyzed. Outcome events were independently assessed using electronic medical records to determine hospitalization for revascularization, new-onset ischemic events, heart failure, cardiovascular, and all-cause death. Differences between LV and RV MRGlu and associations with clinical characteristics and echocardiographic data were evaluated. Associations among FDG PET findings and outcomes were analyzed using Kaplan-Meier survival analysis.


Seventy-five patients (mean age 62.2 ± 12.7 years, male 85.3%, LVEF 19.3 ± 8.6%) were included for analysis. The mean glucose utilization ratio of RV-to-LV (RV/LV MRGlu) was 89.5 ± 264.9% (r = 0.77, p < 0.001). Positive correlations between RV MRGlu and maximal tricuspid regurgitation peak gradient (r = 0.28, p = 0.033) and peak tricuspid regurgitation jet velocity (r = 0.29, p = 0.021) were noted. LVEF was positively correlated with LV MRGlu (r = 0.27, p = 0.018), but negatively correlated with end-diastolic volume (r = − 0.37, p = 0.001), end-systolic volume (r = − 0.54, p < 0.001), and RV/LV MRGlu (r = − 0.40, p < 0.001). However, RV MRGlu was not well correlated with LVEF. Forty-three patients received revascularization procedures after FDG PET, and 13 patients died in a mean follow-up period of 496 ± 453 days (1–1788 days), including nine cardiovascular deaths. Higher RV and LV MRGlu values, LVEF ≤ 16% and LV end-diastolic volume ≥ 209 ml of gated-PET were associated with poor overall survival and cardiac outcomes.


In patients with coronary artery disease and ischemic cardiomyopathy, RV glucose utilization was positively correlated with RV pressure overload, but not LVEF. Global LV and RV MRGlu, LVEF, and LV end-diastolic volume showed significant prognostic value.


Heart failure 18F-fluorodeoxyglucose Positron emission tomography Rate of myocardial glucose uptake Right ventricle 



The authors thank Ms. Ya-Huang Chen, Ms. Chia-Wen Lai, Mr. Chao-Chun Huang and Mr. Po-Wei Li for dynamic PET acquisition, and Dr. Kuan-Yin Ko, Ms. Yu-Shuan Hung, and Mr. Chien-Yu Chu for their assistance in PET analyses and clinical data collection.

Funding information

This study was funded by Ministry of Science and Technology of Taiwan (MOST-101-2314-B-418-012-MY3, MOST-104-2314-B-418-008, MOST-105-2628-B-418-002-MY2, MOST-107-2314-B-418-006-MY3) and Far Eastern Memorial Hospital (FEMH-101-2314-B-418-012-MY3, FEMH-104-2314-B-418-008, FEMH-105-2628-B-418-002-MY2, FEMH-107-2314-B-418-006-MY3).

Compliance with ethical standards

Research involving human participants and/or animals

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

Except for financially supported by the Ministry of Science and Technology of Taiwan (MOST-101-2314-B-418-012-MY3, MOST-104-2314-B-418-008, MOST-105-2628-B-418-002-MY2, MOST-107-2314-B-418-006-MY3) and Far Eastern Memorial Hospital (FEMH-101-2314-B-418-012-MY3, FEMH-104-2314-B-418-008, FEMH-105-2628-B-418-002-MY2, FEMH-107-2314-B-418-006-MY3), no other relevant potential conflicts of interest exist. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Corresponding author Yen-Wen Wu has received research grants from Ministry of Science and Technology of Taiwan and Far Eastern Memorial Hospital. The other authors declare that they have no conflict of interest.


  1. 1.
    Guo Y, Lip GY, Banerjee A. Heart failure in East Asia. Curr Cardiol Rev. 2013;9:112–22.CrossRefGoogle Scholar
  2. 2.
    Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. J Am Coll Cardiol. 2013;62:e147–239.CrossRefGoogle Scholar
  3. 3.
    Savarese G, Lund LH. Global public health burden of heart failure. Card Fail Rev. 2017;3:7–11.CrossRefGoogle Scholar
  4. 4.
    Abebe TB, Gebreyohannes EA, Tefera YG, Abegaz TM. Patients with HFpEF and HFrEF have different clinical characteristics but similar prognosis: a retrospective cohort study. BMC Cardiovasc Disord. 2016;16:232.CrossRefGoogle Scholar
  5. 5.
    Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the heart failure association (HFA) of the ESC. Eur Heart J. 2016;37:2129–200.CrossRefGoogle Scholar
  6. 6.
    Kerkhof PL. Characterizing heart failure in the ventricular volume domain. Clin Med Insights Cardiol. 2015;9:11–31.Google Scholar
  7. 7.
    Reyes EB, Ha JW, Firdaus I, Ghazi AM, Phrommintikul A, Sim D, et al. Heart failure across Asia: same healthcare burden but differences in organization of care. Int J Cardiol. 2016;223:163–7.CrossRefGoogle Scholar
  8. 8.
    Wang CC, Chang HY, Yin WH, Wu YW, Chu PH, Wu CC, et al. TSOC-HFrEF registry: a registry of hospitalized patients with decompensated systolic heart failure: description of population and management. Acta Cardiol Sin. 2016;32:400–11.Google Scholar
  9. 9.
    Wu CK, Juang JJ, Chiang JY, Li YH, Tsai CT, Chiang FT. The Taiwan heart registries: its influence on cardiovascular patient care. J Am Coll Cardiol. 2018;71:1273–83.CrossRefGoogle Scholar
  10. 10.
    Lammertsma AA. Forward to the past: the case for quantitative PET imaging. J Nucl Med. 2017;58:1019–24.CrossRefGoogle Scholar
  11. 11.
    Kluge R, Barthel H, Pankau H, Seese A, Schauer J, Wirtz H, et al. Different mechanisms for changes in glucose uptake of the right and left ventricular myocardium in pulmonary hypertension. J Nucl Med. 2005;46:25–31.Google Scholar
  12. 12.
    Wang L, Li W, Yang Y, Wu W, Cai Q, Ma X, et al. Quantitative assessment of right ventricular glucose metabolism in idiopathic pulmonary arterial hypertension patients: a longitudinal study. Eur Heart J Cardiovasc Imaging. 2016;17:1161–8.CrossRefGoogle Scholar
  13. 13.
    Raina A, Meeran T. Right ventricular dysfunction and its contribution to morbidity and mortality in left ventricular heart failure. Curr Heart Fail Rep. 2018;15:94–105.CrossRefGoogle Scholar
  14. 14.
    Bleasdale RA, Frenneaux MP. Prognostic importance of right ventricular dysfunction. Heart. 2002;88:323–4.CrossRefGoogle Scholar
  15. 15.
    Galie N, McLaughlin VV, Rubin LJ, Simonneau G. An overview of the 6th world symposium on pulmonary hypertension. Eur Respir J. 2019;53:1802148.CrossRefGoogle Scholar
  16. 16.
    Bossone E, D'Andrea A, D'Alto M, Citro R, Argiento P, Ferrara F, et al. Echocardiography in pulmonary arterial hypertension: from diagnosis to prognosis. J Am Soc Echocardiogr. 2013;26:1–14.CrossRefGoogle Scholar
  17. 17.
    Chemla D, Castelain V, Humbert M, Hebert JL, Simonneau G, Lecarpentier Y, et al. New formula for predicting mean pulmonary artery pressure using systolic pulmonary artery pressure. Chest. 2004;126:1313–7.CrossRefGoogle Scholar
  18. 18.
    Parasuraman S, Walker S, Loudon BL, Gollop ND, Wilson AM, Lowery C, et al. Assessment of pulmonary artery pressure by echocardiography-a comprehensive review. Int J Cardiol Heart Vasc. 2016;12:45–51.Google Scholar
  19. 19.
    Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23:685–713.CrossRefGoogle Scholar
  20. 20.
    Austin C, Alassas K, Burger C, Safford R, Pagan R, Duello K, et al. Echocardiographic assessment of estimated right atrial pressure and size predicts mortality in pulmonary arterial hypertension. Chest. 2015;147:198–208.CrossRefGoogle Scholar
  21. 21.
    Ko KY, Wang SY, Yen RF, Shiau YC, Hsu JC, Tsai HY, et al. Clinical significance of quantitative assessment of glucose utilization in patients with ischemic cardiomyopathy. J Nucl Cardiol. 2018.
  22. 22.
    Mäki M, Luotolahti M, Nuutila P, Iida H, Voipio-Pulkki L-M, Ruotsalainen U, et al. Glucose uptake in the chronically dysfunctional but viable myocardium. Circulation. 1996;93:1658–66.CrossRefGoogle Scholar
  23. 23.
    Mannting F, Zabrodina YV, Dass C. Significance of increased right ventricular uptake on 99mTc-sestamibi SPECT in patients with coronary artery disease. J Nucl Med. 1999;40:889–94.Google Scholar
  24. 24.
    Abraham A, Kass M, Ruddy TD, deKemp RA, Lee AK, Ling MC, et al. Right and left ventricular uptake with Rb-82 PET myocardial perfusion imaging: markers of left main or 3 vessel disease. J Nucl Cardiol. 2010;17:52–60.CrossRefGoogle Scholar
  25. 25.
    Mazraeshahi RM, Striet J, Oeltgen RC, Gerson MC. Myocardial SPECT images for diagnosis of pulmonary hypertension and right ventricular hypertrophy. J Nucl Med Technol. 2010;38:175–80.CrossRefGoogle Scholar
  26. 26.
    Melenovsky V, Andersen MJ, Andress K, Reddy YN, Borlaug BA. Lung congestion in chronic heart failure: haemodynamic, clinical, and prognostic implications. Eur J Heart Fail. 2015;17:1161–71.CrossRefGoogle Scholar
  27. 27.
    Passino C, Sironi AM, Favilli B, Poletti R, Prontera C, Ripoli A, et al. Right heart overload contributes to cardiac natriuretic hormone elevation in patients with heart failure. Int J Cardiol. 2005;104:39–45.CrossRefGoogle Scholar
  28. 28.
    Ritt P, Vija H, Hornegger J, Kuwert T. Absolute quantification in SPECT. Eur J Nucl Med Mol Imaging. 2011;38:S69–77.CrossRefGoogle Scholar
  29. 29.
    Feher A, Sinusas AJ. Quantitative assessment of coronary microvascular function: dynamic single-photon emission computed tomography, positron emission tomography, ultrasound, computed tomography, and magnetic resonance imaging. Circ Cardiovasc Imaging. 2017;10:e006427.CrossRefGoogle Scholar
  30. 30.
    Voelkel NF, Quaife RA, Leinwand LA, Barst RJ, McGoon MD, Meldrum DR, et al. Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation. 2006;114:1883–91.CrossRefGoogle Scholar
  31. 31.
    de Keizer B, Scholtens AM, van Kimmenade RRJ, de Jong PA. High FDG uptake in the right ventricular myocardium of a pulmonary hypertension patient. J Am Coll Cardiol. 2013;62:1724.CrossRefGoogle Scholar
  32. 32.
    Drozd K, Ahmadi A, Deng Y, Jiang B, Petryk J, Thorn S, et al. Effects of an endothelin receptor antagonist, Macitentan, on right ventricular substrate utilization and function in a Sugen 5416/hypoxia rat model of severe pulmonary arterial hypertension. J Nucl Cardiol. 2017;24:1979–89.CrossRefGoogle Scholar
  33. 33.
    Vachiery JL, Adir Y, Barbera JA, Champion H, Coghlan JG, Cottin V, et al. Pulmonary hypertension due to left heart diseases. J Am Coll Cardiol. 2013;62:D100–8.CrossRefGoogle Scholar
  34. 34.
    Bokhari S, Raina A, Rosenweig EB, Schulze PC, Bokhari J, Einstein AJ, et al. PET imaging may provide a novel biomarker and understanding of right ventricular dysfunction in patients with idiopathic pulmonary arterial hypertension. Circ Cardiovasc Imaging. 2011;4:641–7.CrossRefGoogle Scholar
  35. 35.
    Ohira H, deKemp R, Pena E, Davies RA, Stewart DJ, Chandy G, et al. Shifts in myocardial fatty acid and glucose metabolism in pulmonary arterial hypertension: a potential mechanism for a maladaptive right ventricular response. Eur Heart J Cardiovasc Imaging. 2016;17:1424–31.CrossRefGoogle Scholar
  36. 36.
    Wu YW, Tadamura E, Yamamuro M, Kanao S, Marui A, Tanabara K, et al. Comparison of contrast-enhanced MRI with (18)F-FDG PET/201Tl SPECT in dysfunctional myocardium: relation to early functional outcome after surgical revascularization in chronic ischemic heart disease. J Nucl Med. 2007;48:1096–103.CrossRefGoogle Scholar
  37. 37.
    Fang W, Zhao L, Xiong CM, Ni XH, He ZX, He JG, et al. Comparison of 18F-FDG uptake by right ventricular myocardium in idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease. Pulm Circ. 2012;2:365–72.CrossRefGoogle Scholar
  38. 38.
    Gibb AA, Hill BG. Metabolic coordination of physiological and pathological cardiac remodeling. Circ Res. 2018;123:107–28.CrossRefGoogle Scholar
  39. 39.
    Zhang X, Schindler TH, Prior JO, Sayre J, Dahlbom M, Huang SC, et al. Blood flow, flow reserve, and glucose utilization in viable and nonviable myocardium in patients with ischemic cardiomyopathy. Eur J Nucl Med Mol Imaging. 2013;40:532–41.CrossRefGoogle Scholar
  40. 40.
    Gall H, Felix JF, Schneck FK, Milger K, Sommer N, Voswinckel R, et al. The Giessen pulmonary hypertension registry: survival in pulmonary hypertension subgroups. J Heart Lung Transplant. 2017;36:957–67.CrossRefGoogle Scholar
  41. 41.
    van der Bruggen CEE, Tedford RJ, Handoko ML, van der Velden J, de Man FS. RV pressure overload: from hypertrophy to failure. Cardiovasc Res. 2017;113:1423–32.CrossRefGoogle Scholar
  42. 42.
    Puwanant S, Park M, Popovic ZB, Tang WH, Farha S, George D, et al. Ventricular geometry, strain, and rotational mechanics in pulmonary hypertension. Circulation. 2010;121:259–66.CrossRefGoogle Scholar
  43. 43.
    Wu YW, Hsu PY, Lin YH, Cheng MF, Ko CL, Huang YH, et al. Diagnostic and prognostic implications of exercise treadmill and rest first-pass radionuclide angiography in patients with pulmonary hypertension. Clin Nucl Med. 2017;42:e392–9.CrossRefGoogle Scholar
  44. 44.
    Hardegree EL, Sachdev A, Fenstad ER, Villarraga HR, Frantz RP, McGoon MD, et al. Impaired left ventricular mechanics in pulmonary arterial hypertension: identification of a cohort at high risk. Circ Heart Fail. 2013;6:748–55.CrossRefGoogle Scholar
  45. 45.
    Hueb T, Rocha MS, Siqueira SF, Nishioka SADO, Peixoto GL, Saccab MM, et al. Impact of diabetes mellitus on ischemic cardiomyopathy. Five-year follow-up. REVISION-DM trial. Diabetol Metab Syndr. 2018;10:19.CrossRefGoogle Scholar
  46. 46.
    Hu L, Qiu C, Wang X, Xu M, Shao X, Wang Y. The association between diabetes mellitus and reduction in myocardial glucose uptake: a population-based 18F-FDG PET/CT study. BMC Cardiovasc Disord. 2018;18:203.CrossRefGoogle Scholar
  47. 47.
    Hansen MS, Andersen A, Tolbod LP, Hansson NH, Nielsen R, Vonk-Noordegraaf A, et al. Levosimendan improves cardiac function and myocardial efficiency in rats with right ventricular failure. Pulm Circ. 2018;8:2045893217743122.Google Scholar
  48. 48.
    Shah KS, Xu H, Matsouaka RA, Bhatt DL, Heidenreich PA, Hernandez AF, et al. Heart failure with preserved, borderline, and reduced ejection fraction: 5-year outcomes. J Am Coll Cardiol. 2017;70:2476–86.CrossRefGoogle Scholar
  49. 49.
    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.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Szu-Ying Tsai
    • 1
    • 2
  • Yen-Wen Wu
    • 1
    • 3
    • 4
    Email author
  • Shan-Ying Wang
    • 1
    • 5
  • Yu-Chien Shiau
    • 1
  • Kuan-Ming Chiu
    • 6
  • Hao-Yuan Tsai
    • 3
  • Chien-Lin Lee
    • 3
  • Jung-Cheng Hsu
    • 3
  • Chung-Ming Tu
    • 3
  • Heng-Hsu Lin
    • 3
  • Shan-Hui Huang
    • 3
  1. 1.Department of Nuclear MedicineFar Eastern Memorial HospitalNew Taipei CityTaiwan
  2. 2.Ministry of Health and Welfare Nantou HospitalNantou CountyTaiwan
  3. 3.Division of Cardiology, Cardiovascular Medical CenterFar Eastern Memorial HospitalNew Taipei CityTaiwan
  4. 4.National Yang-Ming University School of MedicineTaipeiTaiwan
  5. 5.Department of Biomedical Imaging and Radiological SciencesNational Yang-Ming UniversityTaipeiTaiwan
  6. 6.Division of Cardiovascular Surgery, Cardiovascular Medical CenterFar Eastern Memorial HospitalNew Taipei CityTaiwan

Personalised recommendations