Prednisolone to the rescue: Complete functional recovery after severe immune checkpoint inhibitor associated myocarditis with left and right ventricular involvement

Introduction

In clinical studies, immune checkpoint inhibitor (ICI) associated myocarditis was a rare adverse event, though reported mortality rates are as high as 50 %. Right ventricular (RV) involvement during this complication has only once been previously reported.

Case report

A 63-year-old female breast cancer patient presented to our chest pain unit via ambulance 19 days after her fourth ICI (pembrolizumab) dose. She reported palpitations and dizziness, which proved to be caused by recurrent ventricular tachycardia (VT). Using repeated electrical cardioversions and amiodarone, we terminated the VT. Hereafter, significant ST segment elevation in chest leads V 1 - 3 and troponin elevation (2167 ng/l hs troponin T) became apparent. Coronary angiography excluded relevant coronary artery disease. Suspecting ICI associated myocarditis, we discontinued ICI and initiated high-dose parenteral prednisolone (1 g o.d.) immediately in accordance with the modified International Cardio-Oncology Society (IC-OS) 2021 consensus. MRI met the IC-OS major criterion for ICI associated myocarditis only partially. We saw a moderately reduced global left ventricular (LV) ejection fraction of 38 % with regional wall motion abnormalities (WMA), significant regional T2 prolongation and late gadolinium enhancement (LGE). However, LGE and T2 prolongation did not match for all regions. Moreover, we suspected RV involvement due to marked regional WMA of the RV free wall resulting in a severely reduced global RV ejection fraction of 27 %. Notably, there was extensive LGE of the RV free wall. Because of this unusual presentation, we performed LV endomyocardial biopsy (EMB) to confirm the diagnosis. Histopathologic examination revealed extensive acute lymphocytic myocarditis accompanied by numerous cardiomyocyte necroses. Competing differential diagnoses were ruled out, including an acute or persistent infection with cardiotropic viruses. In addition, there was no fibrous or fatty replacement as is the case in arrhythmogenic cardiomyopathy. During hospitalization we documented a stable sinus rhythm, decline in troponin levels and improvement of overall condition. Therefore, we reduced prednisolone dosage and switched to oral administration. We discharged her home with a wearable defibrillator and tapered prednisolone on short interval outpatient follow-ups with clinical, electrocardiographic and troponin level evaluation. Curative surgical breast cancer resection and adjuvant radiotherapy could be performed within the previously scheduled period of time. Five months after initial diagnosis, MRI revealed residual LGE but no oedema and complete functional recovery of LV and RV function. Lastly, we implanted an implantable cardioverter defibrillator for secondary VT prevention.

Discussion

ICI are used to treat a constantly increasing number of malignancies. Therefore, broad awareness for this potentially fatal complication with its wide spectrum of clinical presentation needs to be raised. Timely diagnostics according to published consensus criteria involving troponin dynamics, cardiac MRI and if necessary EMB, are essential for early initiation of high-dose parenteral immunosuppressive therapy, which may salvage even severe cases like the present. This case emphasizes the need for close interdisciplinary collaboration between cardiologists and oncologists, which will become even more important in the future.