Heart Transplantation and the “The Secret Chamber”: How Echocardiographic Assessment of the Right Ventricle Can Reveal Acute Cell Rejection

Cellular Acute Rejection; Heart Transplantation; Endomyocardial Biopsy; Graft Rejection; Echocardiography/methods

Although heart transplantation (Tx) has achieved great technical and scientific evolution in recent decades, acute cell rejection (ACR) still represents an important threat to patients submitted to this procedure. Acute rejection screening protocols associated with early immunosuppressive therapy are essential for Tx success. However, endomyocardial biopsy, although expensive and invasive, is still a reference method for the screening of ACR.

ACR is related to incipient damage in myocardial function,¹ which may not be detected by conventional echocardiographic techniques for myocardial function analysis. Myocardial deformation, analyzed by the speckle tracking technique, is able to detect incipient myocardial dysfunction in several pathologies, among them, ACR after cardiac Tx.²

In a recent meta-analysis of 10 studies with methodological similarities, Elkaryone et al.³ analyzed 511 patients and 1,267 endomyocardial biopsies. The sensitivity of the global longitudinal deformation of the left ventricle (LV), expressed by the GLS, to detect ACR diagnosed by endomyocardial biopsy was 78%, with a specificity of 68%.³ Moreover, changes in LV myocardial deformation have already been demonstrated as independent predictors of clinical outcomes after heart Tx.⁴ It is important to note that echocardiographic images do not always allow the analysis of myocardial deformation in this population, since the transplanted heart may be in more medial position in the thoracic cavity, making it difficult to obtain good quality images, as previously demonstrated.² However, despite studies of LV changes in this scenario, less knowledge has been accumulated to date about the correlations between changes in the right ventricle (RV) and ACR after heart Tx. The increase in the dimensions of this chamber associated with the slight reduction of its systolic function in the natural evolution of patients after cardiac Tx has been established.⁵ - ⁷

The work by Carrion et al.⁸ demonstrate that patients with signs of significant ACR by endomyocardial biopsy have reduced left ventricular diastolic function parameters, in addition to signs of increased LV posterior wall thickness, when compared to those without significant rejection. Unlike other studies, there was no significant difference in the LV longitudinal deformation between this group and the one that did not show signs of significant rejection. It is worth mentioning that most of the previous studies used, for the analysis of myocardial deformation, vendor-dedicated software, while Carrion et al.⁸ used vendor-independent software to analyze the images,⁸ which could explain the aforementioned differences, at least in part, since there is still no standardization between software from different vendors.⁸

Another possible source of divergence between the present study and previous investigations is the methodology used to measure myocardial deformation. Carrion et al.⁸ performed the measurement at the systolic peak of myocardial deformation, as recommended by the most recent international guidelines,⁹ while other studies used the peak myocardial deformation of the entire cardiac cycle.⁹ Also, the software used for the analysis by Carrion et al. is based on the analysis of endocardial deformation, while other software available, and historically more often used, analyzed the myocardial deformation of the entire wall thickness, including all its layers, also called transmural deformation.¹⁰ In this study, the conventional echocardiographic parameters for the analysis of the RV function, as well as the RV myocardial deformation, were significantly reduced in the group of patients with signs of ACR, when compared to those without significant rejection.¹¹ Moreover, the group with moderate ACR also showed changes suggestive of worse LV diastolic function, when compared to the group without significant rejection.

Thus, the question remains whether the involvement of RV systolic function is a primary one, due to ACR, or secondary to the retrograde increase in LV filling pressures. Additionally, not only the myocardial deformation of the RV, but also the conventional parameters for the functional evaluation of this cardiac chamber have shown be significantly different between the two groups studied by Carrion et al.⁸ Previous studies have shown that RV systolic deformation, especially of its free wall, has a greater correlation with RV systolic function, assessed by reference methods, in comparison with conventional echocardiographic parameters, both in ischemic and non-ischemic heart diseases.¹² - ¹⁴ Although the comparison of the diagnostic accuracy of the RV functional parameters for ACR diagnosis has not been addressed by Carrion et al.,⁸ this issue is a relevant point to be clarified in future studies, aiming to guide the use of these techniques in the post-heart Tx clinical routine.

Thus, for a science that recently managed to recognize and “point” to the “chamber of secrets”, i.e., the RV, the work of Carrion et al.⁸ reinforces the importance of its echocardiographic evaluation for the non-invasive detection of incipient myocardial dysfunction related to ACR in patients being followed after heart Tx.

Referências

• ¹
  Ruiz Ortiz M, Pena ML, Mesa D, Delgado M, Romo E, Santisteban M, 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(2):229-37.
• ²
  Badano LP, Miglioranza MH, Edvardsen T, Colafranceschi AS, Muraru D, Bacal F, et al. 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(9):919-48.
• ³
  Elkaryoni A, Altibi AM, Khan MS, Okasha O, Ellakany K, Hassan A, 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(2):302-9.
• ⁴
  Kobayashi Y, Sudini NL, Rhee JW, Aymami M, Moneghetti KJ, Bouajila S, et al. Incremental Value of Deformation Imaging and Hemodynamics Following Heart Transplantation: Insights From Graft Function Profiling. JACC Heart Fail. 2017;5(12):930-9.
• ⁵
  Ingvarsson A, Werther Evaldsson A, Waktare J, Nilsson J, Smith GJ, Stagmo M, et al. Normal Reference Ranges for Transthoracic Echocardiography Following Heart Transplantation. J Am Soc Echocardiogr. 2018;31(3):349-60.
• ⁶
  Monivas Palomero V, Mingo Santos S, Goirigolzarri Artaza J, Rodriguez Gonzalez E, Restrepo Cordoba MA, Jimenez Sanchez D, et al. Two-Dimensional Speckle Tracking Echocardiography in Heart Transplant Patients: Two-Year Follow-Up of Right and Left Ventricular Function. Echocardiography. 2016;33(5):703-13.
• ⁷
  Harrington JK, Richmond ME, Woldu KL, Pasumarti N, Kobsa S, Freud LR. Serial Changes in Right Ventricular Systolic Function Among Rejection-Free Children and Young Adults After Heart Transplantation. J Am Soc Echocardiogr. 2019;32(8):1027-35 e2.
• ⁸
  Carrion JBM, Sperotto A, Nazario R, Goldraich L, Clausell N, Rohde LE, et al. Disfunção ventricular direita e rejeição do transplante cardíaco. Arq Bras Cardiol. 2020; 114(4):638-644.
• ⁹
  Farsalinos KE, Daraban AM, Unlu S, Thomas JD, Badano LP, Voigt JU. Head-to-Head Comparison of Global Longitudinal Strain Measurements among Nine Different Vendors: The EACVI/ASE Inter-Vendor Comparison Study. J Am Soc Echocardiogr. 2015;28(10):1171-81, e2.
• ¹⁰
  Ruiz-Ortiz M, Rodriguez-Diego S, Delgado M, Kim J, Weinsaft JW, Ortega R, et al. Myocardial deformation and acute cellular rejection after heart transplantation: Impact of inter-vendor variability in diagnostic effectiveness. Echocardiography. 2019;36(12):2185-94.
• ¹¹
  Voigt JU, Pedrizzetti G, Lysyansky P, Marwick TH, Houle H, Baumann R, et al. Definitions for a common standard for 2D speckle tracking echocardiography: consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging. J Am Soc Echocardiogr. 2015;28(2):183-93.
• ¹²
  Becker M, Hoffmann R, Kuhl HP, Grawe H, Katoh M, Kramann R, et al. Analysis of myocardial deformation based on ultrasonic pixel tracking to determine transmurality in chronic myocardial infarction. Eur Heart J. 2006;27(21):2560-6.
• ¹³
  Moreira HT, Volpe GJ, Marin-Neto JA, Nwabuo CC, Ambale-Venkatesh B, Gali LG, et al. Right Ventricular Systolic Dysfunction in Chagas Disease Defined by Speckle-Tracking Echocardiography: A Comparative Study with Cardiac Magnetic Resonance Imaging. J Am Soc Echocardiogr. 2017;30(5):493-502.
• ¹⁴
  Lemarie J, Huttin O, Girerd N, Mandry D, Juilliere Y, Moulin F, et al. Usefulness of Speckle-Tracking Imaging for Right Ventricular Assessment after Acute Myocardial Infarction: A Magnetic Resonance Imaging/Echocardiographic Comparison within the Relation between Aldosterone and Cardiac Remodeling after Myocardial Infarction Study. J Am Soc Echocardiogr. 2015;28(7):818-27 e4.

• Short Editorial related to the article: Impaired Right Ventricular Function in Heart Transplant Rejection

Publication Dates

• Publication in this collection
  29 May 2020
• Date of issue
  Apr 2020Apr 2020