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CC BY-NC-ND 4.0 · Indian J Radiol Imaging 2021; 31(04): 946-955
DOI: 10.1055/s-0041-1741098
Review Article

Insight into Noninvasive Radiological Modalities to Detect Heart Transplant Rejection

Dhruva Sharma
1   Department of Cardiothoracic and Vascular Surgery, SMS Medical College and Attached Hospitals, Jaipur, Rajasthan, India
,
Ganapathy Subramaniam
2   Department of Cardiothoracic Surgery, Institute of Heart and Lung Transplant and Mechanical Circulatory Support, MGM Healthcare, Chennai, Tamil Nadu, India
,
Neha Sharma
3   Department of Pharmacology, SMS Medical College and Attached Hospitals, Jaipur, Rajasthan, India
,
Preksha Sharma
4   Department of Anatomy, SMS Medical College and Attached Hospitals, Jaipur, Rajasthan, India
,
Pooja Sharma
5   Department of Cardiology, Eternal Heart Care Centre, Jaipur, Rajasthan, India
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Abstract

Purpose Patients with end-stage heart failure who remain symptomatic even with exemplary medical and device therapy are treated with heart transplantation. Multitudes of endeavor have been contrived during the last decennium in the field of noninvasive tests to rule out heart transplant rejection (HTR). In spite of having supportive literature, noninvasive imaging techniques lack acceptable documentation of clinical robustness, and endomyocardial biopsy (EMB) still remains the gold standard. The aim of this review is to shed light on the existing noninvasive radiological modalities to detect rejection among heart transplant recipients.

Methods A comprehensive search was conducted for this review article on the basis of literature available including scientific databases of PubMed, Embase, and Google Scholar, using keywords of “Heart transplantation,” “Acute allograft rejection,” “Arrhythmias,” “Echocardiography,” “Speckle tracking echocardiography,” and “Cardiac magnetic resonance imaging” from inception until September 2020.

Results After preliminary screening of the databases, details regarding existent noninvasive radiological modalities to detect HTR were gathered and compiled in this review article. Currently, deformation imaging using speckle tracking and T2 time using cardiac magnetic resonance imaging can serve as screening tools based on which further invasive investigations can be planned. Standardization of blood-based and imaging modalities as screening and possible diagnostic tools for rejection would have obvious clinical and financial benefits in the care of growing number of post heart transplant recipients in our country.

Conclusion Diagnosis of allograft rejection in heart transplant recipients through noninvasive techniques is demanding. To unravel the potential of noninvasive radiological modalities that can serve as a standard-of-care test, a prospective multicentric study randomizing noninvasive modality as first strategy versus current EMB-based gold standard of care is the need of the hour.

Keywords

acute allograft rejection - cardiac magnetic resonance imaging - echocardiography - heart transplantation - speckle-tracking echocardiography


Publication History

Article published online:
11 January 2022

© 2022. Indian Radiological Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Sharma D, Sharma N. A potential drug in the armamentarium of post-cardiac transplantation immunosuppression: belatacept. Indian J Thorac Cardiovasc Surg 2020; 36 (06) 625-628
    CrossrefPubMedGoogle Scholar
  • 2 Ludhwani D, Kanmanthareddy A. Heart Transplantation Rejection [Updated 2020 Jun 5]. In: StatPearls [Internet]. Treasure Island: FL: StatPearls Publishing; 2020. Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537057/
    Google Scholar
  • 3 Lu W, Zheng J, Pan XD. et al. Diagnostic performance of cardiac magnetic resonance for the detection of acute cardiac allograft rejection: a systematic review and meta-analysis. J Thorac Dis 2015; 7 (03) 252-263
    PubMedGoogle Scholar
  • 4 Patel JK, Kobashigawa JA. Should we be doing routine biopsy after heart transplantation in a new era of anti-rejection?. Curr Opin Cardiol 2006; 21 (02) 127-131
    CrossrefPubMedGoogle Scholar
  • 5 Elkaryoni A, Altibi AM, Khan MS. et al. Global longitudinal strain assessment of the left ventricle by speckle tracking echocardiography detects acute cellular rejection in orthotopic heart transplant recipients: a systematic review and meta-analysis. Echocardiography 2020; 37 (02) 302-309
    CrossrefPubMedGoogle Scholar
  • 6 Tang Z, Kobashigawa J, Rafiei M, Stern LK, Hamilton M. The natural history of biopsy-negative rejection after heart transplantation. J Transplant 2013; 2013: 236720 DOI: 10.1155/2013/236720.
    CrossrefPubMedGoogle Scholar
  • 7 Berry GJ, Burke MM, Andersen C. et al. The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation. J Heart Lung Transplant 2013; 32 (12) 1147-1162
    CrossrefPubMedGoogle Scholar
  • 8 Peyster EG, Wang C, Ishola F. et al. In situ immune profiling of heart transplant biopsies improves diagnostic accuracy and rejection risk stratification. JACC Basic Transl Sci 2020; 5 (04) 328-340
    CrossrefPubMedGoogle Scholar
  • 9 Olymbios M, Kwiecinski J, Berman DS, Kobashigawa JA. Imaging in heart transplant patients. JACC Cardiovasc Imaging 2018; 11 (10) 1514-1530
    CrossrefPubMedGoogle Scholar
  • 10 Dolan RS, Rahsepar AA, Blaisdell J. et al. Multiparametric cardiac magnetic resonance imaging can detect acute cardiac allograft rejection after heart transplantation. JACC Cardiovasc Imaging 2019; 12 (8 Pt 2): 1632-1641
    CrossrefPubMedGoogle Scholar
  • 11 Costanzo MR, Dipchand A, Starling R. et al; International Society of Heart and Lung Transplantation Guidelines. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant 2010; 29 (08) 914-956
    CrossrefPubMedGoogle Scholar
  • 12 Frigerio M, Pedrazzini G, Merli M, Vitali E. Heart transplantation. In: Savonitto S, ed. Niguarda Cardiovascular Therapy. Roma: Il Pensiero Scientifico Editore; 2006: 437-75
    Google Scholar
  • 13 Goodroe R, Bonnema DD, Lunsford S. et al. Severe left ventricular hypertrophy 1 year after transplant predicts mortality in cardiac transplant recipients. J Heart Lung Transplant 2007; 26 (02) 145-151
    CrossrefPubMedGoogle Scholar
  • 14 Mondillo S, Maccherini M, Galderisi M. Usefulness and limitations of transthoracic echocardiography in heart transplantation recipients. Cardiovasc Ultrasound 2008; 6: 2 DOI: 10.1186/1476-7120-6-2.
    CrossrefPubMedGoogle Scholar
  • 15 Bhatia SJ, Kirshenbaum JM, Shemin RJ. et al. Time course of resolution of pulmonary hypertension and right ventricular remodeling after orthotopic cardiac transplantation. Circulation 1987; 76 (04) 819-826
    CrossrefPubMedGoogle Scholar
  • 16 Dandel M, Hummel M, Müller J. et al. Reliability of tissue Doppler wall motion monitoring after heart transplantation for replacement of invasive routine screenings by optimally timed cardiac biopsies and catheterizations. Circulation 2001; 104 (12, Suppl 1): I184-I191
    CrossrefPubMedGoogle Scholar
  • 17 Palka P, Lange A, Galbraith A. et al. The role of left and right ventricular early diastolic Doppler tissue echocardiographic indices in the evaluation of acute rejection in orthotopic heart transplant. J Am Soc Echocardiogr 2005; 18 (02) 107-115
    CrossrefPubMedGoogle Scholar
  • 18 Wilhelmi M, Pethig K, Wilhelmi M, Nguyen H, Strüber M, Haverich A. Heart transplantation: echocardiographic assessment of morphology and function after more than 10 years of follow-up. Ann Thorac Surg 2002; 74 (04) 1075-1079 , discussion 1079
    CrossrefPubMedGoogle Scholar
  • 19 Clemmensen TS, Eiskjær H, Kofoed-Nielsen PB, Høyer S, Poulsen SH. Case of acute graft failure during suspected humoral rejection with preserved ejection fraction, but severely reduced longitudinal deformation detected by 2D-speckle tracking. Case Rep Transplant 2014; 2014: 173589 DOI: 10.1155/2014/173589.
    CrossrefPubMedGoogle Scholar
  • 20 Kato TS, Oda N, Hashimura K. et al. Strain rate imaging would predict sub-clinical acute rejection in heart transplant recipients. Eur J Cardiothorac Surg 2010; 37 (05) 1104-1110
    CrossrefPubMedGoogle Scholar
  • 21 Friedberg MK. Echocardiographic detection of heart transplant graft dysfunction: a new twist on an old theme. Circ Cardiovasc Imaging 2016; 9 (09) e005439 DOI: 10.1161/CIRCIMAGING.116.005439.
    CrossrefPubMedGoogle Scholar
  • 22 Badano LP, Miglioranza MH, Edvardsen T. et al; Document reviewers. European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation. Eur Heart J Cardiovasc Imaging 2015; 16 (09) 919-948
    CrossrefPubMedGoogle Scholar
  • 23 Smith JD, Stowell JT, Martínez-Jiménez S. et al. Evaluation after orthotopic heart transplant: what the radiologist should know. Radiographics 2019; 39 (02) 321-343
    CrossrefPubMedGoogle Scholar
  • 24 Dandel M, Lehmkuhl H, Knosalla C, Suramelashvili N, Hetzer R. Strain and strain rate imaging by echocardiography - basic concepts and clinical applicability. Curr Cardiol Rev 2009; 5 (02) 133-148
    CrossrefPubMedGoogle Scholar
  • 25 Tseng AS, Gorsi US, Barros-Gomes S. et al. Use of speckle-tracking echocardiography-derived strain and systolic strain rate measurements to predict rejection in transplant hearts with preserved ejection fraction. BMC Cardiovasc Disord 2018; 18 (01) 241
    CrossrefPubMedGoogle Scholar
  • 26 Zhu S, Li M, Tian F. et al. Diagnostic value of myocardial strain using two-dimensional speckle-tracking echocardiography in acute cardiac allograft rejection: a systematic review and meta-analysis. Echocardiography 2020; 37 (04) 561-569
    CrossrefPubMedGoogle Scholar
  • 27 Mirabet S, García-Osuna A, Garcia de Frutos P. et al. High-sensitivity troponin T and soluble form of AXL as long-term prognostic biomarkers after heart transplantation. Dis Markers 2018; 2018: 6243529 DOI: 10.1155/2018/6243529.
    CrossrefPubMedGoogle Scholar
  • 28 Ambardekar AV, Alluri N, Patel AC, Lindenfeld J, Dorosz JL. Myocardial strain and strain rate from speckle-tracking echocardiography are unable to differentiate asymptomatic biopsy-proven cellular rejection in the first year after cardiac transplantation. J Am Soc Echocardiogr 2015; 28 (04) 478-485
    CrossrefPubMedGoogle Scholar
  • 29 Ojha V, Nakra T, Narwal A. et al. Noninvasive detection of cardiac transplant rejection using cardiovascular magnetic resonance: correlation with endomyocardial biopsy. J Pract Cardiovasc Sci 2020; 6: 87-89
    Google Scholar
  • 30 Butler CR, Kim DH, Chow K. et al. Cardiovascular MRI predicts 5-year adverse clinical outcome in heart transplant recipients. Am J Transplant 2014; 14 (09) 2055-2061
    CrossrefPubMedGoogle Scholar
  • 31 Vermes E, Pantaléon C, Auvet A. et al. Cardiovascular magnetic resonance in heart transplant patients: diagnostic value of quantitative tissue markers: T2 mapping and extracellular volume fraction, for acute rejection diagnosis. J Cardiovasc Magn Reson 2018; 20 (01) 59
    CrossrefPubMedGoogle Scholar
  • 32 Şimşek E, Nalbantgil S, Ceylan N. et al. Diagnostic performance of late gadolinium enhancement in the assessment of acute cellular rejection after heart transplantation. Anatol J Cardiol 2016; 16 (02) 113-118
    PubMedGoogle Scholar
  • 33 Greenway SC, Dallaire F, Kantor PF. et al. Magnetic resonance imaging of the transplanted pediatric heart as a potential predictor of rejection. World J Transplant 2016; 6 (04) 751-758
    CrossrefPubMedGoogle Scholar
  • 34 Battikha CE, Selevany I, Kim PJ. Advances and new insights in post-transplant care: from sequencing to imaging. Curr Treat Options Cardiovasc Med 2020; 22: 32 DOI: 10.1007/s11936-020-00828-8.
    CrossrefGoogle Scholar
  • 35 Garcia J, Liu SZ, Louie AY. Biological effects of MRI contrast agents: gadolinium retention, potential mechanisms and a role for phosphorus. Philos Trans- Royal Soc, Math Phys Eng Sci 2017; 375 (2107): 20170180 DOI: 10.1098/rsta.2017.0180.
    CrossrefPubMedGoogle Scholar
  • 36 Idée J-M, Fretellier N, Robic C, Corot C. The role of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: a critical update. Crit Rev Toxicol 2014; 44 (10) 895-913
    CrossrefPubMedGoogle Scholar
  • 37 Krishna Gokhale AG, Balakrishnan KR, Punnen J. et al. Recommendations of the INSHLT task force for thoracic organ transplant during COVID-19 pandemic in India. J Pract Cardiovasc Sci 2020; 6: 108-110
    CrossrefGoogle Scholar
  • 38 Antończyk K, Niklewski T, Antończyk R, Zakliczyński M, Zembala M, Kukulski T. Speckle-tracking echocardiography for monitoring acute rejection in transplanted heart. Transplant Proc 2018; 50 (07) 2090-2094
    CrossrefPubMedGoogle Scholar
  • 39 Sade LE, Hazirolan T, Kozan H. et al. T1 mapping by cardiac magnetic resonance and multidimensional speckle-tracking strain by echocardiography for the detection of acute cellular rejection in cardiac allograft recipients. JACC Cardiovasc Imaging 2019; 12 (8 Pt 2): 1601-1614
    CrossrefPubMedGoogle Scholar
  • 40 Mingo-Santos S, Moñivas-Palomero V, Garcia-Lunar I. et al. Usefulness of two-dimensional strain parameters to diagnose acute rejection after heart transplantation. J Am Soc Echocardiogr 2015; 28 (10) 1149-1156
    CrossrefPubMedGoogle Scholar
  • 41 Ruiz Ortiz M, Peña ML, Mesa D. et al. Impact of asymptomatic acute cellular rejection on left ventricle myocardial function evaluated by means of two-dimensional speckle tracking echocardiography in heart transplant recipients. Echocardiography 2015; 32 (02) 229-237
    CrossrefPubMedGoogle Scholar
  • 42 Clemmensen TS, Løgstrup BB, Eiskjaer H, Høyer S, Poulsen SH. The long-term influence of repetitive cellular cardiac rejections on left ventricular longitudinal myocardial deformation in heart transplant recipients. Transpl Int 2015; 28 (04) 475-484
    CrossrefPubMedGoogle Scholar
  • 43 Krieghoff C, Barten MJ, Hildebrand L. et al. Assessment of sub-clinical acute cellular rejection after heart transplantation: comparison of cardiac magnetic resonance imaging and endomyocardial biopsy. Eur Radiol 2014; 24 (10) 2360-2371
    CrossrefPubMedGoogle Scholar
  • 44 Imran M, Wang L, McCrohon J. et al. Native T1 mapping in the diagnosis of cardiac allograft rejection: a prospective histologically validated study. JACC Cardiovasc Imaging 2019; 12 (8 Pt 2): 1618-1628
    CrossrefPubMedGoogle Scholar
  • 45 Sethi N, Doshi A, Doshi T. et al. Quantitative cardiac magnetic resonance T2 imaging offers ability to non-invasively predict acute allograft rejection in children. Cardiol Young 2020; 30 (06) 852-859
    CrossrefPubMedGoogle Scholar