key: cord-0874990-2iglukjk
authors: Gopalan, Radha; Mitchel, Hayley; Martinez, Brandon; Wojtaszek, Evelina; Kalya, Anantharam; Arabia, Francisco; Uber, Patricia
title: The Effect Of COVID-19 Infection On Tacrolimus Metabolism In Heart Transplant
date: 2022-04-30
journal: Journal of Cardiac Failure
DOI: 10.1016/j.cardfail.2022.03.321
sha: 291d79d111848426e42b03b04ded6144bbfc5cc5
doc_id: 874990
cord_uid: 2iglukjk

Introduction There is limited knowledge regarding the effects of COVID-19 in heart transplant recipients. Reliance on tacrolimus levels has become a cornerstone of management strategy to balance the immune response with the potential for rejection of the graft. How COVID-19 and its treatment affect tacrolimus metabolism in solid organ transplant is not well understood. Here we present a case of a heart transplant recipient with highly elevated tacrolimus levels following COVID-19 infection despite little to no tacrolimus administration and no other known drug-drug interactions. Case Presentation The patient is a 58-year-old male with history of ischemic cardiomyopathy; status post orthotopic heart transplantation 6/17/2018. The postoperative course was complicated by two occurrences of 2R cellular rejection within 1 year, RV dysfunction, calcineurin induced renal dysfunction, and relative bradycardia. In 7/2020, the patient presented to the ED with complaints of jaw pain, symptoms of urinary retention and 3 days of diarrhea. COVID-19 PCR returned positive. Before infection, the patient had been maintained on a steady dose of tacrolimus 0.5mg BID for 8 months with associated trough levels between the goal range of 4-8ng/mL. At the time of infection, the patient's tacrolimus was held to account for elevated trough levels, and he was then maintained on a dose of 0.5mg QAD for the next 8 months. Discussion Tacrolimus metabolism is represented in Graph 1 via trough:dose (T:D) ratio (T:D ratio measured in 48-hr intervals as the patient was on QAD dosing post-infection). T:D ratio remained stable on tacrolimus 0.5mg BID before COVID-19 infection. Following infection, the ratio sharply rose and remained elevated 8 months later despite reducing the dose to 0.5mg QAD. To our knowledge, this is the first case presented of a heart transplant recipient with altered tacrolimus metabolism status post COVID-19 infection without apparent drug-drug interaction. This suggests a relationship between SARS-COV-2 viremia with tacrolimus metabolism.

The Effect Of COVID-19 Infection On Tacrolimus Metabolism In Heart Transplant RADHA GOPALAN 1 , HAYLEY MITCHEL 1 , BRANDON MARTINEZ 1 , EVELINA WOJTASZEK 2 , ANANTHARAM KALYA 1 , FRANCISCO ARABIA 1 , PATRICIA UBER 1 ; 1 BANNER UNIVERSITY MEDICAL CENTER PHOENIX, PHOENIX, AZ; 2 RJW BARNABAS, JERSEY CITY, NJ Introduction: There is limited knowledge regarding the effects of COVID-19 in heart transplant recipients. Reliance on tacrolimus levels has become a cornerstone of management strategy to balance the immune response with the potential for rejection of the graft. How COVID-19 and its treatment affect tacrolimus metabolism in solid organ transplant is not well understood. Here we present a case of a heart transplant recipient with highly elevated tacrolimus levels following COVID-19 infection despite little to no tacrolimus administration and no other known drug-drug interactions. Case Presentation: The patient is a 58-year-old male with history of ischemic cardiomyopathy; status post orthotopic heart transplantation 6/17/2018. The postoperative course was complicated by two occurrences of 2R cellular rejection within 1 year, RV dysfunction, calcineurin induced renal dysfunction, and relative bradycardia. In 7/ 2020, the patient presented to the ED with complaints of jaw pain, symptoms of urinary retention and 3 days of diarrhea. COVID-19 PCR returned positive. Before infection, the patient had been maintained on a steady dose of tacrolimus 0.5mg BID for 8 months with associated trough levels between the goal range of 4-8ng/mL. At the time of infection, the patient's tacrolimus was held to account for elevated trough levels, and he was then maintained on a dose of 0.5mg QAD for the next 8 months. Discussion: Tacrolimus metabolism is represented in Graph 1 via trough:dose (T:D) ratio (T:D ratio measured in 48-hr intervals as the patient was on QAD dosing post-infection). T:D ratio remained stable on tacrolimus 0.5mg BID before COVID-19 infection. Following infection, the ratio sharply rose and remained elevated 8 months later despite reducing the dose to 0.5mg QAD. To our knowledge, this is the first case presented of a heart transplant recipient with altered tacrolimus metabolism status post COVID-19 infection without apparent drug-drug interaction. This suggests a relationship between SARS-COV-2 viremia with tacrolimus metabolism. T a g g e d P Background: Many specialists are involved in the diagnosis and treatment of transthyretin cardiac amyloidosis (ATTR-CM) due to the variety of associated symptoms. Clinicians are therefore challenged to manage ATTR-CM as patient care progresses from diagnosis to treatment. We sought to determine if an online, virtual patient simulation (VPS)-based continuing medical education intervention could improve performance of cardiologists and primary care physicians (PCPs) related to individualized strategies to diagnose and treat ATTR-CM. Methods: The intervention comprised two patients presenting in a VPS platform that allows learners to order lab tests, make diagnoses, and prescribe treatments in a manner matching the scope and depth of actual practice. Tailored clinical guidance (CG), based on current evidence and expert recommendation, was provided following each decision, followed by the opportunity for the learners to modify their decisions. Decisions were collected post-CG and compared with each user's baseline (pre-CG) decisions using a McNemar's test to determine significant levels of pre-to post-CG change in clinical decisions made with P values < .05 being considered as significant. Data were collected from December 22, 2020 through February 3, 2021. Results: Significant absolute improvements were observed after CG for the following: Cardiologists (n= 91)

Bone scintigraphy: 17% improvement (P<.001) Gene sequencing: 21% improvement (P<.001) Tafamadis: 39% improvement (P<.001) Discontinue metroprolol: 57% improvement (P<.001) Patient education: 8% improvement (P<.01) Patient monitoring: 10% improvement (P<.01) Referral to amyloidosis treatment center: 6% improvement (P<.05) PCPs (n= 149) Diagnose Wildtype ATTR-CM: 25% improvement (P<.001) Order/Initiate ECG: 3% improvement (P<.05) Urine immunofixation electrophoresis: 12% improvement (P<.001) Serum Kappa/Lambda Free Light Chain Ratio: 14% improvement (P<.001) Serum Immunofixation Electrophoresis: 14% improvement (P<.001) Bone scintigraphy: 10% improvement (P<.001) Gene sequencing: 17% improvement

Patient education: 8% improvement (P<.01) Patient monitoring: 9% improvement (P<.01) Referral to amyloidosis treatment center: 9% improvement (P<.001) Conclusion: VPS that immerses and engages specialists in an authentic, patient-based, practical learning environment can significantly improve evidence-based clinical decision making for diagnosis and treatment of

Not All Ventricular Arrhytmias Require A Reduction In LVAD Speed. DAPHNE J. GARCIA GALAN 1 , GREGORY P. MILLIGAN 2 , AMIT ALAM 2 , AMARINDER BINDRA 2 , ROBERT L. GOTTLIEB 2 ; 1 TEXAS A&M UNIVERSITY HEALTH SCIENCE CENTER COLLEGE OF MEDICINE, BRYAN, TX; 2 BAYLOR UNIVERSITY MEDICAL CENTER, DALLAS, TX Background: Despite hemodynamic optimization, ventricular arrhythmias following left ventricular assist device (LVAD) may persist. We present a case in which transthoracic echocardiogram (TTE) paired with LVAD waveform analysis at time of ventricular arrhythmias assisted in differential diagnosis for the precipitating etiology and helped guide management decisions. Case: A 78year-old African American male with stage D heart failure due to ischemic cardiomyopathy underwent implantation of a HeartWare LVAD. Post-operatively, the patient was weaned off inotropes and pressors with gradual speed adjusted to 2600 rpm over the course of a week. Following optimization, he had several episodes of ventricular tachycardia and ventricular fibrillation requiring defibrillation. The likely etiology of trigger was from a fascicular based premature ventricular contraction or suck down event from speed optimization. Intracardiac hemodynamics with Swan-Ganz catheter revealed normal filling pressures, cardiac index and pulmonary vascular resistance with low suspicion for right ventricular failure. An echocardiogram was without evidence of cardiac tamponade. Furthermore, at the time of TTE, another ventricular arrhythmia was captured (Figure 1 ). The inflow cannula was visualized to be well-positioned and there was no suction event, despite the ongoing arrhythmia. The left ventricle was not excessively decompressed either with an LVIDD at 4.9 cm with speed increased to 2700 rpm. HeartWare waveforms were visualized real-time without evidence of speed drops or alarms. The patient remained hemodynamically stable with a mean arterial pressure of 78 mmHg. He was successfully managed with metoprolol and sotalol. Conclusion: Real-time waveforms on LVAD paired with a TTE can aide in the management in patients with ventricular arrhythmias. As this case demonstrates, not all ventricular arrhythmias merit a reduction in speed, particularly in those patients with normal pulmonary vascular resistance. T a g g e d P T a g g e d E n d T a g g e d E n d HFSA Abstracts 2022 HFSA S125