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Number 17- : Progressive cardiomyopathy in a renal transplant patient
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PROGRESSIVE CARDIOMYOPATHY IN A RENAL TRANSPLANT PATIENT

Jason Craft1, Karolina Zareba1, Subha Raman1

1 The Ohio State University Wexner Medical Center, Columbus OH, USA

 

Clinical history

A 37 year old female presented with progressively worsening dyspnea and orthopnea for 3 months. Her background history included bicuspid aortic valve and systemic lupus erythematosus (SLE) with renal transplantation (2007) complicated by post-transplant lymphoproliferative disorder.  Her previous chemotherapy regimen included rituximab and EPOCH (prednisone, etoposide, vincristine, and cyclophosphamide) in 2011, which achieved complete remission.  At that time, she had normal left ventricular systolic function with an ejection fraction of 60-65% by echocardiography.  Subsequently, in 2013 her Ebstein Barr Virus (EBV) PCR was elevated at 83,674 copies/ml, with repeat echocardiogram demonstrating mildly decreased global LV systolic function, LVEF 45-50%.  The EBV viremia persisted through 2016, requiring modification of anti-rejection medications.

The patient’s EKG is seen below demonstrating normal sinus rhythm, 1st degree AV block, left atrial enlargement, left axis deviation, old anterolateral/lateral myocardial infarction, right bundle branch block, and non-specific ST depressions (.5 mm) in the anterior leads V2 and V3.  (Figure 1)

 

 

An echocardiogram performed on the current admission demonstrated moderate to severe global left ventricular systolic dysfunction, LVEF 30-35%, and no significant valvular abnormalities. (Echocardiogram not shown)

Additional laboratory studies included an erythrocyte sedimentation rate of 58 mm/hr (normal <20 mm/hr); B-type natriuretic peptide 2487 pg/ml (normal 0 - 100 pg/mL); negative anti-double stranded DNA immunofixation, and normal C3 complement level.  EBV PCR currently detected <2000 copies/ml (within normal reference range). 

Because of the left ventricular dysfunction, she underwent invasive coronary angiography (Figure 2), which demonstrated a 75% stenosis in the proximal first obtuse marginal artery, and TIMI 2 flow in the distal left anterior descending artery (LAD). 

 

 

(Figure 2) Invasive coronary angiography demonstrating 75% stenosis in the proximal first obtuse marginal artery and TIMI 2 flow in the distal LAD.

 

Subsequently, she underwent a CMR examination to evaluate for possible myocarditis given the history of persistent EBV viremia and SLE.  

 

CMR findings

CMR was performed using a 1.5 T Siemens Avanto.  

(Figure 3) Cine imaging revealed a dilated left ventricle with normal wall thickness and severely reduced LV systolic function (LVEF 29%), with akinesis of the apical anterior, inferior and lateral walls, plus basal anterolateral and inferolateral walls.  A bicuspid aortic valve (type 1) was demonstrated without evidence of stenosis or regurgitation.  The aortic dimensions were normal.

 

(Figure 4) T2 mapping was performed using a T2 prepped bSSFP sequence (T2Prep duration of 0, 24, and 55 ms), and revealed mildly elevated myocardial T2 of 60 ms (normal reference range <60 ms in our laboratory) involving the mid anteroseptum.

 

(Figure 5) Native T1 mapping using a 3-5 MOLLI acquisition scheme demonstrated a value of 1050 ms. 

 

(Figure 6) PSIR LGE acquired 10 minutes post contrast demonstrated prominent epicardial late gadolinium enhancement (LGE) involving the inferior, anterolateral, and inferolateral walls becoming transmural in some segments, plus prominent mid-wall LGE involving the septum, and near transmural infarction scar involving the distal LAD territory. 

 

Endomyocardial biopsy demonstrated mild, focal interstitial edema without active inflammatory infiltrates; fine granular staining in endothelial cells with IgG, IgA, C1q, C3, kappa, and lambda; and mild isolated small arterial staining with IgM. The overall findings were non-specific.  

 

 

 

Conclusions

Differential diagnosis in our patient included ischemic heart disease, infectious myocarditis, SLE myocarditis, drug induced cardiomyopathy, and idiopathic dilated cardiomyopathy.  Given the findings on coronary angiogram and CMR, we concluded that her cardiomyopathy was likely due to a combination of ischemic heart disease and chronic viral myocarditis.  The elevated erythrocyte sedimentation rate and myocardial T2 did suggest presence of active inflammation; however viral PCR titers had decreased to the reference range with adjustment of anti-rejection medications.  Furthermore, the area of T2 weighted abnormality was small and focal, incorporating only one myocardial segment (the mid anteroseptum).  Unfortunately, we believe extensive myocardial scarring had occurred in the previous months to years when viremia was present.  Given all the clinical information, treatment for EBV was not instituted.  A hypercoagulability workup was negative, and the patient was treated medically for her coronary artery disease. 

 

Perspective

Diagnosis and management of viral myocarditis continues to be challenging given its varying clinical manifestation and etiology. Presentations vary from chest pain syndromes, to ventricular arrhythmias, and acute decompensated congestive heart failure with dilated cardiomyopathy. It is important to realize that endomyocardial biopsy is only 45% sensitive for the detection of myocarditis1.  

CMR has greatly impacted diagnosis of myocarditis with the use of T2 parametric mapping and late gadolinium enhancement imaging2. Depending on the stage of presentation and etiology, therapeutic decision options may differ.  However, further research is needed to determine optimal medical treatment strategies.  

For allograft transplant recipients, EBV viremia is typically addressed by lowering the level of immunosuppression3.  Since the presentation in our case was dilated cardiomyopathy, the focus was on standard goal directed therapy for systolic congestive heart failure.   One of the largest randomized, controlled treatment trials, the Myocarditis Treatment Trial, failed to show a benefit from immunosuppressive therapy in addition to standard heart failure therapy. At one year, there was no difference in mortality or left ventricular ejection fraction in patients treated with a combination of prednisone and either azathioprine or cyclosporine versus placebo4.  Monoclonal antibodies stimulating CD40 during the viral replication period or deactivation of helper T cell immune responses 1, 2, and 17 have shown some promise in experimental autoimmune myocarditis (EAM) animal models5.  Interferon beta or ganciclovir therapy may be of benefit in patients with enteroviral/adenoviral/parvovirus B19 cardiomyopathy or human herpes virus-6 myocarditis respectively.  Intravenous immunoglobulin may be of benefit in patients who have not yet developed dilated cardiomyopathy6.    Lastly patients treated with colchicine may demonstrate improvement in T2 weighted abnormalities on follow-up CMR imaging6.

 

Click here to view all CMR images on CloudCMR.

 

 

References

1.     From AM, Maleszewski JJ, Rihal CS.  Current status of endomyocardial biopsy.  Mayo Clin Proc.  Nov 2011; 86(11): 1095–1102

2.     Thavendiranathan P, Walls M, Giri S, et al.  Improved detection of myocardial involvement in acute inflammatory cardiomyopathies using T2 mapping.  Circ Cardiovasc Imaging. 2012;5:102-110

3.     San-Juan R, Comoli P, Caillard S, et al.  Epstein-Barr virus-related post-transplant lymphoproliferative disorder in solid organ transplant recipients.  Lancet. Sept 2014; 20(suppl 7), 109–118

4.     Kindermann I, Barth C, Mahfoud F, et al.  Update on myocarditis.  Lancet.  28 Feb 2012; 59(9): 779-792

5.    Li-na HAN, Shuang HE, Yu-tang W.  Review: Advances in monoclonal antibody application in myocarditis.  J Zhejiang Univ-Sci B (Biomed & Biotechnol) 2013 14(8):676-687

6.     Dominguez F, Kuhl U, Pieske B, et al.  Update on myocarditis and inflammatory cardiomyopathy: reemergence of endomyocardial biopsy.  Rev Esp Cardiol. 2016;69(2):178–187

7.     Morgenstern D, Lisko J, Boniface NC, et al.  Myocarditis and colchicine: a new perspective from cardiac MRI.  J Cardiovascular Magnetic Resonance 2016 18(Suppl 1):O100 

 

 

Case prepared by Associate Editor: Dr Rebecca Kozor. University of Sydney, Australia.

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