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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 6  |  Issue : 1  |  Page : 87-89

Noninvasive detection of cardiac transplant rejection using cardiovascular magnetic resonance: Correlation with endomyocardial biopsy


1 Department of Cardiovascular Radiology and Endovascular Interventions, All India Institute of Medical Sciences, New Delhi, India
2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
3 Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India

Date of Submission01-Jan-2020
Date of Decision02-Mar-2020
Date of Acceptance02-Mar-2020
Date of Web Publication17-Apr-2020

Correspondence Address:
Priya Jagia
Room No. 10A, Department of Cardiovascular Radiology and Endovascular Interventions, All India Institute of Medical Sciences, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpcs.jpcs_1_20

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  Abstract 


A heart transplant patient came for her routine annual surveillance. She received cardiac transplant in April 2017. The patient did not have any cardiovascular symptoms. Her coronary angiogram did not reveal any significant coronary artery disease. The endomyocardial biopsy showed diagnosis of acute cellular rejection, Grade 1R with antibody mediated rejection, Grade 2 and Quilty effect was made. Subsequently, panel-reactive antibody assay was performed, and it was 0% for human leukocyte antigen (HLA) Class I and 43% for HLA Class II. A noncontrast cardiac magnetic resonance imaging (MRI) (mapping sequence) was done to rule out any rejection. Cine images revealed normal biventricular function. However, mapping sequences showed diffuse abnormal increase in native T1 (average ~1200 ms) and native T2 (average ~62 ms) values in the entire myocardium. MRI T1 and T2 mapping sequences may help in early non invasive detection of rejection.

Keywords: Biopsy, heart transplant, MRI, non-invasive diagnosis, T1 and T2 mapping


How to cite this article:
Ojha V, Nakra T, Narwal A, Ganga KP, Arava S, Ray R, Seth S, Jagia P. Noninvasive detection of cardiac transplant rejection using cardiovascular magnetic resonance: Correlation with endomyocardial biopsy. J Pract Cardiovasc Sci 2020;6:87-9

How to cite this URL:
Ojha V, Nakra T, Narwal A, Ganga KP, Arava S, Ray R, Seth S, Jagia P. Noninvasive detection of cardiac transplant rejection using cardiovascular magnetic resonance: Correlation with endomyocardial biopsy. J Pract Cardiovasc Sci [serial online] 2020 [cited 2020 Aug 3];6:87-9. Available from: http://www.j-pcs.org/text.asp?2020/6/1/87/282798



A 20-year-old female heart transplant patient came for her routine annual surveillance. She received cardiac transplant in April 2017. Her previous endomyocardial biopsies did not show any evidence of rejection. The patient did not have any cardiovascular symptoms. Her coronary angiogram did not reveal any significant coronary artery disease. A noncontrast cardiac magnetic resonance imaging (MRI) (mapping sequence) was done to rule out any rejection. Cine images revealed normal biventricular function. However, mapping sequences showed diffuse increase in native T1 (average ~1200 ms) and native T2 (average ~62 ms) values in the entire myocardium [Figure 1]a and [Figure 1]b. The time required to complete the scan was 8 minutes, with only limited sequences.
Figure 1: Cardiac magnetic resonance-derived T1 mapping (a) and T2 mapping (b) images reveal raised T1 (1127.19 ms) and T2 (61.55 ms) values. Endomyocardial biopsy: (c) shows Quilty effect and interfiber lymphocytic infiltrate (immunopositive for CD3 [inset]) with interstitial edema. (d) Shows histopathogical section with blood vessels showing plump endothelial cells. C4d immunostaining in interstitial capillaries (inset).

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Postcardiac transplant surveillance biopsy comprised three endomyocardial fragments. One of the fragments revealed admixtures of CD3 (T-cells) and CD20 (B-cells) positive lymphocytes identified predominantly within the endocardium along with conspicuous vascularity, suggestive of Qulity lesion. Myocytes showed mild hypertrophy and nucleomegaly. Interstitium displayed perimyocytic fibrosis and edema. There was focal interfiber lymphocytic infiltrate (CD3 positive) without any significant myonecrosis. Blood vessels were lined by plump endothelial cells with obliteration of lumen at places, along with presence of an occasional neutrophil in the wall. Immunohistochemistry for C4d highlighted more than 50 % of interstitial capillaries with moderate staining intensity. Based on the overall findings, the diagnosis of acute cellular rejection, Grade 1R[1] with antibody mediated rejection, Grade 2[2] and Quilty effect was made. Subsequently, panel-reactive antibody assay was performed, and it was 0% for human leukocyte antigen (HLA) Class I and 43% for HLA Class II [Figure 1]c and [Figure 1]d.

Cardiac magnetic resonance-derived myocardial T1 and T2 values are newer imaging biomarkers for early noninvasive detection of acute cardiac allograft rejection. T1 and T2 mapping values for normal population is 900–1020 ms and 43–55 ms, respectively, at 1.5 Tesla MRI, as standardized in our scanner. [Figure 2] shows T1 and T2 mapping values in a normal adult for comparison. Many studies have shown that T2 values are significantly raised in heart transplant recipients with allograft rejection compared to those without rejection [Table 1].[3],[4],[5] A recent study has also shown the excellent negative predictive value of noncontrast T1 mapping for noninvasive detection of rejection if the T1 values are more than 1029 ms, when compared to biopsy [Table 1].[6] Moreover, use of a rapid MRI protocol, as in our case, substantially reduces the duration of cardiac MR examination and tissue characterization can be done without the need for gadolinium contrast. This is especially important as many of these patients are on nephrotoxic drugs for immunosuppression. Myocardial tissue characterization using noninvasive methods such as T1 and T2 mapping holds substantial promise to obviate the requirement of endomyocardial biopsy in cardiac transplant recipients.
Figure 2: The normal T1 and T2 mapping values in a normal adult.

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Table 1: Studies evaluating diagnostic accuracy of T1 and T2 mapping in cardiac transplant patients

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Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Stewart S, Winters GL, Fishbein MC, Tazelaar HD, Kobashigawa J, Abrams J, et al. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant 2005;24:1710-20.  Back to cited text no. 1
    
2.
Berry GJ, Burke MM, Andersen C, Bruneval P, Fedrigo M, Fishbein MC, 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;32:1147-62.  Back to cited text no. 2
    
3.
Butler CR, Savu A, Bakal JA, Toma M, Thompson R, Chow K, et al. Correlation of cardiovascular magnetic resonance imaging findings and endomyocardial biopsy results in patients undergoing screening for heart transplant rejection. J Heart Lung Transplant 2015;34:643-50.  Back to cited text no. 3
    
4.
Usman AA, Taimen K, Wasielewski M, McDonald J, Shah S, Giri S, et al. Cardiac magnetic resonance T2 mapping in the monitoring and follow-up of acute cardiac transplant rejection: A pilot study. Circ Cardiovasc Imaging 2012;5:782-90.  Back to cited text no. 4
    
5.
Vermes E, Pantaléon C, Auvet A, Cazeneuve N, Machet MC, Delhommais 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;20:59.  Back to cited text no. 5
    
6.
Imran M, Wang L, McCrohon J, Yu C, Holloway C, Otton J, et al. Native T1 mapping in the diagnosis of cardiac allograft rejection: A prospective histologically validated study. JACC Cardiovasc Imaging 2019;12:1618-28.  Back to cited text no. 6
    


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