THE SPORADIC DYSRHYTHMIA OF TACROLIMUS IN AN ORTHOTOPIC HEART

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Immunosuppressive therapy is essential for organ transplanted patients. One such broadly used agent is the commonly used macrolide antibiotic tacrolimus. Tacrolimus has several well-known adverse effects including nephrotoxicity, neurotoxicity, infection, diarrhea. Reports of supraventricular tachycardia as a side effect of tacrolimus are rare. CASE PRESENTATION: We present a 48-year-old male with a history of non-ischemic cardiomyopathy status post orthotopic heart transplant who presented to the hospital due to sudden onset palpitations with mild diaphoresis which lasted 30 minutes in duration. Patient reported some mild diaphoresis but no shortness of breath, chest pain, lightheadedness, or dizziness. The patient stated that he had been experiencing episodes of tachycardia for the last few months but none that had persisted to this extent. He reported medication compliance. His vitals were Temp 98.4, BP 140/88, HR 260, RR 20. After review of his EKG, he was diagnosed with supraventricular tachycardia (SVT) (referenced EKG is after adenosine administration). The patient was hospitalized a few months prior to admission for COVID 19 infection and acute pulmonary embolism. His transplant antirejection regimen was changed from sirolimus to tacrolimus during this prior hospitalization due to the increased risk of thrombosis associated with sirolimus in view of the recognized prothrombic effects of COVID-19. Incidentally, the patient started experiencing sporadic episodes of tachycardia since this change in his medication regimen. In the emergency department, diagnostic studies such as troponins, CBC, BMP, magnesium, hepatic panel, TSH, CMV DNA were within normal parameters for the patient. Tacrolimus blood concentration level was found to be 17 with a goal normal level between 4 to 6. The patient had a right/left heart catheterization with endomyocardial biopsy which showed no evidence of coronary artery vasculopathy or acute cellular rejection, thereby ruling out other potential causes of his SVT. His tacrolimus dose was subsequently decreased with significant improvement in the frequency of his symptoms and no further reported episodes of SVT (with further tacrolimus levels not exceeding 7). DISCUSSION: The mechanism by which tacrolimus leads to SVT is not well understood. One purported mechanism is through the inhibition of the calcineurin-calcium-calmodulin complex. Calcium calmodulin is coincidentally also used by smooth muscle cells to contract. It is thought that by inhibiting this system, there is a subsequent increase in vasodilation which leads to the increased sympathetic and adrenergic response, thereby increasing the risk of arrhythmias such as SVT. CONCLUSIONS: Incessant dysrhythmias caused by tacrolimus can be life-threatening, whereby we seek to raise awareness of the importance of carefully monitoring patients on this drug. REFERENCE #1: Kim BR, Shin HS, Jung YS, Rim H. A case of tacrolimus-induced supraventricular arrhythmia after kidney transplantation. Sao Paulo Med J. 2013;131(3):205-207. doi:10.1590/1516-3180.2013.1313472 REFERENCE #2: Pires SDS, Oliveira R, Moradas-Ferreira P, Mendes MV. The Onset of Tacrolimus Biosynthesis in Streptomyces tsukubaensis Is Dependent on the Intracellular Redox Status. Antibiotics (Basel). 2020;9(10):703. Published 2020 Oct 15. doi:10.3390/antibiotics9100703 REFERENCE #3: Wojciechowski D, Wiseman A. Long-Term Immunosuppression Management: Opportunities and Uncertainties [published online ahead of print, 2021 Apr 14]. Clin J Am Soc Nephrol. 2021;CJN.15040920. doi:10.2215/CJN.15040920 DISCLOSURES: No relevant relationships by Jamarcus Brider, source=Web Response No relevant relationships by Ahamed Khalyfa, source=Web Response No relevant relationships by Navkiran Randhawa, source=Web Response