Skip to main content

Advertisement

Log in

Negative synergism of diabetes mellitus and obesity in patients with heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study

  • Original Paper
  • Published:
The International Journal of Cardiovascular Imaging Aims and scope Submit manuscript

Abstract

In patients with heart failure with preserved ejection fraction (HFpEF), diabetes mellitus (DM) and obesity are important comorbidities as well as major risk factors. Their conjoint impact on the myocardium provides insight into the HFpEF aetiology. We sought to investigate the association between obesity, DM, and their combined effect on alterations in the myocardial tissue in HFpEF patients. One hundred and sixty-two HFpEF patients (55 ± 12 years, 95 men) and 45 healthy subjects (53 ± 12 years, 27 men) were included. Patients were classified according to comorbidity prevalence (36 obese patients without DM, 53 diabetic patients without obesity, and 73 patients with both). Myocardial remodeling, fibrosis, and longitudinal contractility were quantified with cardiovascular magnetic resonance imaging using cine and myocardial native T1 images. Patients with DM and obesity had impaired global longitudinal strain (GLS) and increased myocardial native T1 compared to patients with only one comorbidity (DM + Obesity vs. DM and Obesity; GLS, − 15 ± 2.1 vs − 16.5 ± 2.4 and − 16.7 ± 2.2%; native T1, 1162 ± 37 vs 1129 ± 25 and 1069 ± 29 ms; P < 0.0001 for all). A negative synergistic effect of combined obesity and DM prevalence was observed for native T1 (np2 = 0.273, p = 0.002) and GLS (np2 = 0.288, p < 0.0001). Additionally, severity of insulin resistance was associated with GLS (R = 0.590, P < 0.0001), and native T1 (R = 0.349, P < 0.0001). The conjoint effect of obesity and DM in HFpEF patients is associated with diffuse myocardial fibrosis and deterioration in GLS. The negative synergistic effects observed on the myocardium may be related to severity of insulin resistance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. TE Owan HD, Herges RM, Jacobsen SJ, Roger VL, Redfield MM (2006) Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 355:251–259

    Article  CAS  Google Scholar 

  2. Shah SJ, Heitner JF, Sweitzer NK, Anand IS, Kim HY, Harty B, Boineau R, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Lewis EF, Markov V, O’Meara E, Kobulia B, Shaburishvili T, Solomon SD, Pitt B, Pfeffer MA, Li R (2013) Baseline characteristics of patients in the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial. Circ Heart Fail 6(2):184–192. https://doi.org/10.1161/CIRCHEARTFAILURE.112.972794

    Article  CAS  PubMed  Google Scholar 

  3. Chirinos JA, Bhattacharya P, Kumar A, Proto E, Konda P, Segers P, Akers SR, Townsend RR, Zamani P (2019) Impact of diabetes mellitus on ventricular structure, arterial stiffness, and pulsatile hemodynamics in heart failure with preserved ejection fraction. J Am Heart Assoc 8(4):e011457. https://doi.org/10.1161/JAHA.118.011457

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lindman BR, Davila-Roman VG, Mann DL, McNulty S, Semigran MJ, Lewis GD, de las Fuentes L, Joseph SM, Vader J, Hernandez AF, Redfield MM (2014) Cardiovascular phenotype in HFpEF patients with or without diabetes: a RELAX trial ancillary study. J Am Coll Cardiol 64(6):541–549. https://doi.org/10.1016/j.jacc.2014.05.030

    Article  PubMed  PubMed Central  Google Scholar 

  5. McHugh K, DeVore AD, Wu J, Matsouaka RA, Fonarow GC, Heidenreich PA, Yancy CW, Green JB, Altman N, Hernandez AF (2019) Heart failure with preserved ejection fraction and diabetes: JACC state-of-the-art review. J Am Coll Cardiol 73(5):602–611. https://doi.org/10.1016/j.jacc.2018.11.033

    Article  PubMed  Google Scholar 

  6. Samson R, Jaiswal A, Ennezat PV, Cassidy M, Le Jemtel TH (2016) Clinical phenotypes in heart failure with preserved ejection fraction. J Am Heart Assoc 5(1):e002154. https://doi.org/10.1161/JAHA.115.002477

    Article  Google Scholar 

  7. Tromp J, Tay WT, Ouwerkerk W, Teng TK, Yap J, MacDonald MR, Leineweber K, McMurray JJV, Zile MR, Anand IS, Richards AMR, Lam CSP, Authors AH (2018) Multimorbidity in patients with heart failure from 11 Asian regions: a prospective cohort study using the ASIAN-HF registry. PLoS Med 15(3):e1002541. https://doi.org/10.1371/journal.pmed.1002541

    Article  PubMed  PubMed Central  Google Scholar 

  8. Tsujimoto T, Kajio H (2017) Abdominal obesity is associated with an increased risk of all-cause mortality in patients with HFpEF. J Am Coll Cardiol 70(22):2739–2749. https://doi.org/10.1016/j.jacc.2017.09.1111

    Article  PubMed  Google Scholar 

  9. Packer M, Kitzman DW (2018) Obesity-related heart failure with a preserved ejection fraction: the mechanistic rationale for combining inhibitors of aldosterone, neprilysin, and sodium-glucose cotransporter-2. JACC Heart Fail 6(8):633–639. https://doi.org/10.1016/j.jchf.2018.01.009

    Article  Google Scholar 

  10. Pandey A, Patel KV, Vaduganathan M, Sarma S, Haykowsky MJ, Berry JD, Lavie CJ (2018) Physical activity, fitness, and obesity in heart failure with preserved ejection fraction. JACC Heart Fail 6(12):975–982. https://doi.org/10.1016/j.jchf.2018.09.006

    Article  Google Scholar 

  11. Savji N, Meijers WC, Bartz TM, Bhambhani V, Cushman M, Nayor M, Kizer JR, Sarma A, Blaha MJ, Gansevoort RT, Gardin JM, Hillege HL, Ji F, Kop WJ, Lau ES, Lee DS, Sadreyev R, van Gilst WH, Wang TJ, Zanni MV, Vasan RS, Allen NB, Psaty BM, van der Harst P, Levy D, Larson M, Shah SJ, de Boer RA, Gottdiener JS, Ho JE (2018) The association of obesity and cardiometabolic traits with incident HFpEF and HFrEF. JACC Heart Fail 6(8):701–709. https://doi.org/10.1016/j.jchf.2018.05.018

    Article  PubMed  PubMed Central  Google Scholar 

  12. Altara R, Giordano M, Norden ES, Cataliotti A, Kurdi M, Bajestani SN, Booz GW (2017) Targeting obesity and diabetes to treat heart failure with preserved ejection fraction. Front Endocrinol 8:160. https://doi.org/10.3389/fendo.2017.00160

    Article  Google Scholar 

  13. Dalos D, Mascherbauer J, Zotter-Tufaro C, Duca F, Kammerlander AA, Aschauer S, Bonderman D (2016) Functional status, pulmonary artery pressure, and clinical outcomes in heart failure with preserved ejection fraction. J Am Coll Cardiol 68(2):189–199. https://doi.org/10.1016/j.jacc.2016.04.052

    Article  PubMed  Google Scholar 

  14. Obokata M, Reddy YNV, Pislaru SV, Melenovsky V, Borlaug BA (2017) Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction. Circulation 136(1):6–19. https://doi.org/10.1161/CIRCULATIONAHA.116.026807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gulsin GS, Kanagala P, Chan DCS, Cheng ASH, Athithan L, Graham-Brown MPM, Singh A, Yang J, Li Z, Khunti K, Davies MJ, Arnold JR, Squire IB, Ng LL, McCann GP (2019) Differential left ventricular and left atrial remodelling in heart failure with preserved ejection fraction patients with and without diabetes. Ther Adv Endocrinol Metab 10:2042018819861593. https://doi.org/10.1177/2042018819861593

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kristensen SL, Mogensen UM, Jhund PS, Petrie MC, Preiss D, Win S, Kober L, McKelvie RS, Zile MR, Anand IS, Komajda M, Gottdiener JS, Carson PE, McMurray JJ (2017) Clinical and echocardiographic characteristics and cardiovascular outcomes according to diabetes status in patients with heart failure and preserved ejection fraction: a report from the i-preserve trial (irbesartan in heart failure with preserved ejection fraction). Circulation 135(8):724–735. https://doi.org/10.1161/CIRCULATIONAHA.116.024593

    Article  PubMed  Google Scholar 

  17. Scherbakov N, Bauer M, Sandek A, Szabo T, Topper A, Jankowska EA, Springer J, von Haehling S, Anker SD, Lainscak M, Engeli S, Dungen HD, Doehner W (2015) Insulin resistance in heart failure: differences between patients with reduced and preserved left ventricular ejection fraction. Eur J Heart Fail 17(10):1015–1021. https://doi.org/10.1002/ejhf.317

    Article  CAS  PubMed  Google Scholar 

  18. Lindman BR (2017) The diabetic heart failure with preserved ejection fraction phenotype: is it real and is it worth targeting therapeutically? Circulation 135(8):736–740. https://doi.org/10.1161/CIRCULATIONAHA.116.025957

    Article  PubMed  Google Scholar 

  19. Ashrafian H, Frenneaux MP, Opie LH (2007) Metabolic mechanisms in heart failure. Circulation 116(4):434–448. https://doi.org/10.1161/circulationaha.107.702795

    Article  CAS  PubMed  Google Scholar 

  20. Cauwenberghs N, Knez J, Thijs L, Haddad F, Vanassche T, Yang WY, Wei FF, Staessen JA, Kuznetsova T (2018) Relation of insulin resistance to longitudinal changes in left ventricular structure and function in a general population. J Am Heart Assoc 7(7):e008315. https://doi.org/10.1161/JAHA.117.008315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Haykowsky MJ, Nicklas BJ, Brubaker PH, Hundley WG, Brinkley TE, Upadhya B, Becton JT, Nelson MD, Chen H, Kitzman DW (2018) Regional adipose distribution and its relationship to exercise intolerance in older obese patients who have heart failure with preserved ejection fraction. JACC Heart Fail 6(8):640–649. https://doi.org/10.1016/j.jchf.2018.06.002

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ingelsson ESJ, Arnlöv J, Zethelius B, Lind L (2005) Insulin resistance and risk of congestive heart failure. JAMA 294(3):334–341

    Article  CAS  Google Scholar 

  23. Steinberger J, Daniels SR, American Heart Association Atherosclerosis H, Obesity in the Young C, American Heart Association Diabetes C (2003) Obesity, insulin resistance, diabetes, and cardiovascular risk in children: an American Heart Association scientific statement from the Atherosclerosis, Hypertension, and Obesity in the Young Committee (Council on Cardiovascular Disease in the Young) and the Diabetes Committee (Council on Nutrition, Physical Activity, and Metabolism). Circulation 107(10):1448–1453. https://doi.org/10.1161/01.cir.0000060923.07573.f2

    Article  PubMed  Google Scholar 

  24. Kanagala P, Cheng ASH, Singh A, Khan JN, Gulsin GS, Patel P, Gupta P, Arnold JR, Squire IB, Ng LL, McCann GP (2019) Relationship between focal and diffuse fibrosis assessed by CMR and clinical outcomes in heart failure with preserved ejection fraction. JACC Cardiovasc Imaging. https://doi.org/10.1016/j.jcmg.2018.11.031

    Article  PubMed  Google Scholar 

  25. Kanagala P, Cheng ASH, Singh A, McAdam J, Marsh AM, Arnold JR, Squire IB, Ng LL, McCann GP (2018) Diagnostic and prognostic utility of cardiovascular magnetic resonance imaging in heart failure with preserved ejection fraction—implications for clinical trials. J Cardiovasc Magn Reson 20(1):4. https://doi.org/10.1186/s12968-017-0424-9

    Article  PubMed  PubMed Central  Google Scholar 

  26. Su MY, Lin LY, Tseng YH, Chang CC, Wu CK, Lin JL, Tseng WY (2014) CMR-verified diffuse myocardial fibrosis is associated with diastolic dysfunction in HFpEF. JACC Cardiovasc Imaging 7(10):991–997. https://doi.org/10.1016/j.jcmg.2014.04.022

    Article  PubMed  Google Scholar 

  27. Kato S, Saito N, Kirigaya H, Gyotoku D, Iinuma N, Kusakawa Y, Iguchi K, Nakachi T, Fukui K, Futaki M, Iwasawa T, Taguri M, Kimura K, Umemura S (2015) Prognostic significance of quantitative assessment of focal myocardial fibrosis in patients with heart failure with preserved ejection fraction. Int J Cardiol 191:314–319. https://doi.org/10.1016/j.ijcard.2015.05.048

    Article  PubMed  Google Scholar 

  28. Pathan F, Puntmann VO, Nagel E (2018) Role of cardiac magnetic resonance in heart failure with preserved ejection fraction. Curr Cardiovasc Imaging Rep 11(5):8. https://doi.org/10.1007/s12410-018-9450-8

    Article  Google Scholar 

  29. Nakamori S, Dohi K, Ishida M, Goto Y, Imanaka-Yoshida K, Omori T, Goto I, Kumagai N, Fujimoto N, Ichikawa Y, Kitagawa K, Yamada N, Sakuma H, Ito M (2018) Native T1 mapping and extracellular volume mapping for the assessment of diffuse myocardial fibrosis in dilated cardiomyopathy. JACC Cardiovasc Imaging 11(1):48–59. https://doi.org/10.1016/j.jcmg.2017.04.006

    Article  PubMed  Google Scholar 

  30. Kammerlander AA, Kraiger JA, Nitsche C, Dona C, Duca F, Zotter-Tufaro C, Binder C, Aschauer S, Loewe C, Hengstenberg C, Bonderman D, Mascherbauer J (2019) Global longitudinal strain by CMR feature tracking is associated with outcome in HFPEF. JACC Cardiovasc Imaging. https://doi.org/10.1016/j.jcmg.2019.02.016

    Article  PubMed  Google Scholar 

  31. Paulus WJ, Tschope C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, Marino P, Smiseth OA, De Keulenaer G, Leite-Moreira AF, Borbely A, Edes I, Handoko ML, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser AG, Brutsaert DL (2007) How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J 28(20):2539–2550. https://doi.org/10.1093/eurheartj/ehm037

    Article  PubMed  Google Scholar 

  32. Reddy YNV, Carter RE, Obokata M, Redfield MM, Borlaug BA (2018) A simple, evidence-based approach to help guide diagnosis of heart failure with preserved ejection fraction. Circulation 138(9):861–870. https://doi.org/10.1161/CIRCULATIONAHA.118.034646

    Article  PubMed  PubMed Central  Google Scholar 

  33. Shah SJ, Lam CSP, Svedlund S, Saraste A, Hage C, Tan RS, Beussink-Nelson L, Ljung Faxen U, Fermer ML, Broberg MA, Gan LM, Lund LH (2018) Prevalence and correlates of coronary microvascular dysfunction in heart failure with preserved ejection fraction: PROMIS-HFpEF. Eur Heart J 39(37):3439–3450. https://doi.org/10.1093/eurheartj/ehy531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelista A (2009) Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr 22(2):107–133. https://doi.org/10.1016/j.echo.2008.11.023

    Article  PubMed  Google Scholar 

  35. De Castro S, Caselli S, Maron M, Pelliccia A, Cavarretta E, Maddukuri P, Cartoni D, Di Angelantonio E, Kuvin JT, Patel AR, Pandian NG (2007) Left ventricular remodelling index (LVRI) in various pathophysiological conditions: a real-time three-dimensional echocardiographic study. Heart 93(2):205–209. https://doi.org/10.1136/hrt.2006.093997

    Article  PubMed  Google Scholar 

  36. Sundström JLL, Nyström N, Zethelius B, Andrén B, Hales CN, Lithell HO (2000) Left ventricular concentric remodeling rather than left ventricular hypertrophy is related to the insulin resistance syndrome in elderly men. Circulation 101(22):2595–2600

    Article  Google Scholar 

  37. Shah RV, Abbasi SA, Neilan TG, Hulten E, Coelho-Filho O, Hoppin A, Levitsky L, de Ferranti S, Rhodes ET, Traum A, Goodman E, Feng H, Heydari B, Harris WS, Hoefner DM, McConnell JP, Seethamraju R, Rickers C, Kwong RY, Jerosch-Herold M (2013) Myocardial tissue remodeling in adolescent obesity. J Am Heart Assoc 2(4):e000279. https://doi.org/10.1161/JAHA.113.000279

    Article  PubMed  PubMed Central  Google Scholar 

  38. Weingartner S, Roujol S, Akcakaya M, Basha TA, Nezafat R (2015) Free-breathing multislice native myocardial T1 mapping using the slice-interleaved T1 (STONE) sequence. Magn Reson Med 74(1):115–124. https://doi.org/10.1002/mrm.25387

    Article  CAS  PubMed  Google Scholar 

  39. Roujol S, Foppa M, Weingartner S, Manning WJ, Nezafat R (2015) Adaptive registration of varying contrast-weighted images for improved tissue characterization (ARCTIC): application to T1 mapping. Magn Reson Med 73(4):1469–1482. https://doi.org/10.1002/mrm.25270

    Article  PubMed  Google Scholar 

  40. Zhu Y, Kang J, Duan C, Nezafat M, Neisius U, Jang J, Nezafat R (2019) Integrated motion correction and dictionary learning for free-breathing myocardial T1 mapping. Magn Reson Med 81(4):2644–2654. https://doi.org/10.1002/mrm.27579

    Article  PubMed  Google Scholar 

  41. Khan SH, Sobia F, Niazi NK, Manzoor SM, Fazal N, Ahmad F (2018) Metabolic clustering of risk factors: evaluation of Triglyceride-glucose index (TyG index) for evaluation of insulin resistance. Diabetol Metab Syndr 10:74. https://doi.org/10.1186/s13098-018-0376-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Won KB, Park GM, Lee SE, Cho IJ, Kim HC, Lee BK, Chang HJ (2018) Relationship of insulin resistance estimated by triglyceride glucose index to arterial stiffness. Lipids Health Dis 17(1):268. https://doi.org/10.1186/s12944-018-0914-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lim J, Kim J, Koo SH, Kwon GC (2019) Comparison of triglyceride glucose index, and related parameters to predict insulin resistance in Korean adults: an analysis of the 2007-2010 Korean National Health and Nutrition Examination Survey. PLoS ONE 14(3):e0212963. https://doi.org/10.1371/journal.pone.0212963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Er LK, Wu S, Chou HH, Hsu LA, Teng MS, Sun YC, Ko YL (2016) Triglyceride glucose-body mass index is a simple and clinically useful surrogate marker for insulin resistance in nondiabetic individuals. PLoS ONE 11(3):e0149731. https://doi.org/10.1371/journal.pone.0149731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Li S, Guo B, Chen H, Shi Z, Li Y, Tian Q, Shi S (2019) The role of the triglyceride (triacylglycerol) glucose index in the development of cardiovascular events: a retrospective cohort analysis. Sci Rep 9(1):7320. https://doi.org/10.1038/s41598-019-43776-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Paulus WJ, Tschope C (2013) A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol 62(4):263–271. https://doi.org/10.1016/j.jacc.2013.02.092

    Article  PubMed  Google Scholar 

  47. Brandt MM, Nguyen ITN, Krebber MM, van de Wouw J, Mokry M, Cramer MJ, Duncker DJ, Verhaar MC, Joles JA, Cheng C (2019) Limited synergy of obesity and hypertension, prevalent risk factors in onset and progression of heart failure with preserved ejection fraction. J Cell Mol Med 23(10):6666–6678. https://doi.org/10.1111/jcmm.14542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. McQueen AP, Zhang D, Hu P, Swenson L, Yang Y, Zaha VG, Hoffman JL, Yun UJ, Chakrabarti G, Wang Z, Albertine KH, Abel ED, Litwin SE (2005) Contractile dysfunction in hypertrophied hearts with deficient insulin receptor signaling: possible role of reduced capillary density. J Mol Cell Cardiol 39(6):882–892. https://doi.org/10.1016/j.yjmcc.2005.07.017

    Article  CAS  PubMed  Google Scholar 

  49. Horwich TB, Fonarow GC (2010) Glucose, obesity, metabolic syndrome, and diabetes relevance to incidence of heart failure. J Am Coll Cardiol 55(4):283–293. https://doi.org/10.1016/j.jacc.2009.07.029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ferreira VMPS, Dall’Armellina E, Karamitsos TD, Francis JM, Ntusi N, Holloway C, Choudhury RP, Kardos A, Robson MD, Friedrich MG, Neubauer S (2014) Native T1-mapping detects the location, extent and patterns of acute myocarditis without the need for gadolinium contrast agents. J Cardiovasc Magn Reson 23(16):36

    Article  Google Scholar 

  51. Haaf P, Garg P, Messroghli DR, Broadbent DA, Greenwood JP, Plein S (2016) Cardiac T1 mapping and extracellular volume (ECV) in clinical practice: a comprehensive review. J Cardiovasc Magn Reson 18(1):89. https://doi.org/10.1186/s12968-016-0308-4

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

Dr. Nezafat receives grant funding from the National Institutes of Health 1R01HL129185-01, 1R01HL129157, and 1R01HL127015 (Bethesda, MD, USA); and the American Heart Association (AHA) 15EIA22710040 (Waltham, MA, USA). The funders had no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Reza Nezafat.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interests.

Ethical approval

The study protocol was approved by the Beth Israel Deaconess Medical Center Institutional Review Board.

Informed Consent

A written informed consent was obtained from each study participant.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 12 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kucukseymen, S., Neisius, U., Rodriguez, J. et al. Negative synergism of diabetes mellitus and obesity in patients with heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study. Int J Cardiovasc Imaging 36, 2027–2038 (2020). https://doi.org/10.1007/s10554-020-01915-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-020-01915-4

Keywords

Navigation