Utility of a fusion protein T-cell co-stimulation blocker Belatacept in heart transplant recipients: Real world experience from a high volume center.

BACKGROUND: Belatacept (BTC), a fusion protein, selectively inhibits T-cell co-stimulation by binding to the CD80 and CD86 receptors on antigen-presenting cells (APCs) and has been used as immunosuppression in adult renal transplant recipients. However, data regarding its use in heart transplant (HT) recipients are limited. This retrospective cohort study aimed to delineate BTC's application in HT, focusing on efficacy, safety, and associated complications at a high-volume HT center. METHODS: A retrospective cohort study was conducted of patients who underwent HT between January 2017 and December 2021 and subsequently received BTC as part of their immunosuppressive regimen. Twenty-one HT recipients were identified. Baseline characteristics, history of rejection, and indication for BTC use were collected. Outcomes included renal function, graft function, allograft rejection and mortality. Follow-up data were collected through December 2023. RESULTS: Among 776 patients monitored from January 2017 to December 2021 21 (2.7%) received BTC treatment. Average age at transplantation was 53 years (± 12 years), and 38% were women. BTC administration began, on average, 689 [483, 1830] days post-HT. The primary indications for BTC were elevated pre-formed donor-specific antibodies in highly sensitized patients (66.6%) and renal sparing (23.8%), in conjunction with reduced calcineurin inhibitor dosage. Only one (4.8%) patient encountered rejection within a year of starting BTC. Graft function by echocardiography remained stable at 6 and 12 months posttreatment. An improvement was observed in serum creatinine levels (76.2% of patients), decreasing from a median of 1.58 to 1.45 (IQR [1.0-2.1] to [1.1-1.9]) over 12 months (p = .054). eGFR improved at 3 and 6 months compared with 3 months pre- BTC levels; however, this was not statistically significant (p = .24). Treatment discontinuation occurred in seven patients (33.3%) of whom four (19%) were switched back to full dose CNI. Infections occurred in 11 patients (52.4%), leading to BTC discontinuation in 4 patients (19%). CONCLUSION: In this cohort, BTC therapy was used as alternative immunosuppression for management of highly sensitized patients or for renal sparing. BTC therapy when combined with CNI dose reduction resulted in stabilization in renal function as measured through renal surrogate markers, which did not, however, reach statistical significance. Patients on BTC maintained a low rejection rate and preserved graft function. Infections were common during BTC therapy and were associated with medication pause/discontinuation in 19% of patients. Further randomized studies are needed to assess the efficacy and safety of BTC in HT recipients.

The Difference Between Cystatin C- and Creatinine-Based Estimated GFR in Heart Failure With Reduced Ejection Fraction: Insights From PARADIGM-HF.

RATIONALE & OBJECTIVE: The clinical implications of the discrepancy between cystatin C (cysC)- and serum creatinine (Scr)-estimated glomerular filtration rate (eGFR) in patients with heart failure (HF) and reduced ejection fraction (HFrEF) are unknown. STUDY DESIGN: Post-hoc analysis of randomized trial data. SETTING & PARTICIPANTS: 1,970 patients with HFrEF enrolled in PARADIGM-HF with available baseline cysC and Scr measurements. EXPOSURE: Intraindividual differences between eGFR based on cysC (eGFRcysC) and Scr (eGFRScr; eGFRdiffcysC-Scr). OUTCOMES: Clinical outcomes included the PARADIGM-HF primary end point (composite of cardiovascular [CV] mortality or HF hospitalization), CV mortality, all-cause mortality, and worsening kidney function. We also examined poor health-related quality of life (HRQoL), frailty, and worsening HF (WHF), defined as HF hospitalization, emergency department visit, or outpatient intensification of therapy between baseline and 8-month follow-up. ANALYTICAL APPROACH: Fine-Gray subdistribution hazard models and Cox proportional hazards models were used to regress clinical outcomes on baseline eGFRdiffcysC-Scr. Logistic regression was used to investigate the association of baseline eGFRdiffcysC-Scr with poor HRQoL and frailty. Linear regression models were used to assess the association of WHF with eGFRcysC, eGFRScr, and eGFRdiffcysC-Scr at 8-month follow-up. RESULTS: Baseline eGFRdiffcysC-Scr was higher than +10 and lower than-10mL/min/1.73m2 in 13.0% and 35.7% of patients, respectively. More negative values of eGFRdiffcysC-Scr were associated with worse outcomes ([sub]hazard ratio per standard deviation: PARADIGM-HF primary end point, 1.18; P=0.008; CV mortality, 1.34; P=0.001; all-cause mortality, 1.39; P<0.001; worsening kidney function, 1.31; P=0.05). For a 1-standard-deviation decrease in eGFRdiffcysC-Scr, the prevalences of poor HRQoL and frailty increased by 29% and 17%, respectively (P≤0.008). WHF was associated with a more pronounced decrease in eGFRcysC than in eGFRScr, resulting in a change in 8-month eGFRdiffcysC-Scr of-4.67mL/min/1.73m2 (P<0.001). LIMITATIONS: Lack of gold-standard assessment of kidney function. CONCLUSIONS: In patients with HFrEF, discrepancies between eGFRcysC and eGFRScr are common and are associated with clinical outcomes, HRQoL, and frailty. The decline in kidney function associated with WHF is more marked when assessed with eGFRcysC than with eGFRScr. PLAIN-LANGUAGE SUMMARY: Kidney function assessment traditionally relies on serum creatinine (Scr) to establish an estimated glomerular filtration rate (eGFR). However, this has been challenged with the introduction of an alternative marker, cystatin C (cysC). Muscle mass and nutritional status have differential effects on eGFR based on cysC (eGFRcysC) and Scr (eGFRScr). Among ambulatory patients with heart failure enrolled in PARADIGM-HF, we investigated the clinical significance of the difference between eGFRcysC and eGFRScr. More negative values (ie, eGFRScr>eGFRcysC) were associated with worse clinical outcomes (including mortality), poor quality of life, and frailty. In patients with progressive heart failure, which is characterized by muscle loss and poor nutritional status, the decline in kidney function was more pronounced when eGFR was estimated using cysC rather than Scr.

HFSA Expert Consensus Statement on the Medical Management of Patients on Durable Mechanical Circulatory Support.

The medical management of patients supported with durable continuous flow left ventricular assist device (LVAD) support encompasses pharmacological therapies administered in the preoperative, intraoperative, postoperative, and chronic LVAD support stages. As patients live longer on LVAD support, the risks of LVAD-related complications and progression of cardiovascular and other diseases increase. Using existing data from cohort studies, registries, randomized trials, and expert opinion, this Heart Failure Society of America Consensus Document on the Medical Management of Patients on Durable Mechanical Circulatory Support offers best practices on the management of patients on durable mechanical circulatory support, focusing on pharmacological therapies administered to patients on continuous flow LVADs. Although quality data in the LVAD population are few, the use of guideline-directed heart failure medical therapies and the importance of blood pressure management, right ventricular preload and afterload optimization, and antiplatelet and anticoagulation regimens are discussed. Recommended pharmacological regimens used to mitigate or treat common complications encountered during LVAD support, including arrhythmias, vasoplegia, mucocutaneous bleeding, and infectious complications, are addressed. Finally, this document touches on important potential pharmacological interactions from antidepressants and herbal and nutritional supplements of relevance to providers of patients on LVAD support.

PCSK9 inhibitors safely and effectively lower LDL after heart transplantation: a systematic review and meta-analysis.

Coronary allograft vasculopathy (CAV) continues to afflict a high number of heart transplant (HT) recipients, and elevated LDL is a key risk factor. Many patients cannot tolerate statin medications after HT; however, data for alternative agents remains scarce. To address this key evidence gap, we evaluated the safety and efficacy of the PCSK9i after HT through systematic review and meta-analysis. We searched Medline, Cochrane Central, and Scopus from the earliest date through July 15th, 2021. Citations were included if they were a report of PCSK9i use in adults after HT and reported an outcome of interest. Outcomes included change in LDL cholesterol from baseline, incidence of adverse events, and evidence of CAV. Changes from baseline and outcome incidences were pooled using contemporary random-effects model methodologies. A total of six studies including 97 patients were included. Over a mean follow-up of 13 months (range 3-21), PCSK9i use lowered LDL by 82.61 mg/dL (95% CI - 119.15 to - 46.07; I2 = 82%) from baseline. Serious adverse drug reactions were rarely reported, and none was attributable to the PCSK9i therapy. Four studies reported stable calcineurin inhibitor levels during PCSK9i initiation. One study reported outcomes in 33 patients with serial coronary angiography and intravascular ultrasound, and PCSK9i were associated with stable coronary plaque thickness and lumen area. One study reported on immunologic safety, showing no DSA development within 1 month of therapy. Preliminary data suggest that long-term PCSK9i therapy is safe, significantly lowers LDL, and may attenuate CAV after HT. Additional study on larger cohorts is warranted to confirm these findings.

Early clinical experience with nirmatrelvir/ritonavir for the treatment of COVID-19 in solid organ transplant recipients.

Nirmatrelvir/ritonavir (NR) use has not yet been described in solid organ transplant recipients (SOTRs) with mild COVID-19. The objective was to evaluate outcomes among SOTR and describe the drug-drug interaction of NR. This is an IRB-approved, retrospective study of all adult SOTR on a calcineurin inhibitor (CNI) or mammalian target of rapamycin inhibitor who were prescribed NR between December 28, 2021 and January 6, 2022. A total of 25 adult SOTR were included (n = 21 tacrolimus, n = 4 cyclosporine, n = 3 everolimus, n = 1 sirolimus). All patients were instructed to follow the following standardized protocol during treatment with 5 days of NR: hold tacrolimus or mTOR inhibitor or reduce cyclosporine dose to 20% of baseline daily dose. Four patients (16%) were hospitalized by day 30; one for infectious diarrhea and three for symptoms related to COVID-19. No patients died within 30 days of receipt of NR. Median tacrolimus level pre- and post-NR were 7.4 ng/ml (IQR, 6.6-8.6) and 5.2 (IQR, 3.6-8.7), respectively. Four patients experienced a supratherapeutic tacrolimus concentration after restarting tacrolimus post-NR. Our results show the clinically significant interaction between NR and immunosuppressive agents can be reasonably managed with a standardized dosing protocol. Prescribers should carefully re-introduce CNI after the NR course is complete.

COVID-19 therapeutics and outcomes among solid organ transplant recipients during the Omicron BA.1 era.

Treatment outcomes associated with the use of novel COVID-19 therapeutics in solid organ transplant recipients (SOTR) are not well described in the literature. The objective of this analysis was to characterize 30-day hospitalization and other key secondary endpoints experienced by outpatient SOTR with mild-moderate COVID-19 treated with nirmatrelvir/ritonavir (NR), sotrovimab, or no SARS-CoV-2 specific treatment. This IRB-approved, retrospective study included 154 SOTR with a documented positive SARS-CoV-2 infection between December 16, 2021 and January 19, 2022 (a predominant Omicron BA.1 period in New York City). Patients who received NR (N = 28) or sotrovimab (N = 51) experienced a lower rate of 30-day hospitalization or death as compared to those who received no specific treatment (N = 75) (p = .009). A total of three deaths occurred, all among patients who initially received no specific treatment prior to hospitalization. These results suggest a role for SARS-CoV-2 specific agents in the treatment of SOTR with COVID-19, and that there does not appear to be any difference in effectiveness when comparing NR versus sotrovimab.

Chronic intermittent intravenous immunoglobulin in heart transplant recipients with elevated donor-specific antibody levels.

Donor-specific antibodies (DSA) are associated with antibody-mediated rejection (AMR) and poor patient survival. In heart transplant, the efficacy of intermittent intravenous immunoglobulin (IVIg) in reducing de novo DSA levels and treating AMR has not been characterized. We retrospectively studied a cohort of 19 patients receiving intermittent IVIg for elevated DSA and examined changes in DSA levels and graft function. Intermittent IVIg infusions were generally safe and well tolerated. Overall, 23 of 62 total DSA (37%) were undetectable after treatment, 21 DSA (34%) had MFI decrease by more than 25%, and 18 (29%) had MFI decrease by less than 25% or increase. The average change in MFI was -51% ± 71% (P < .001). Despite reductions in DSA, among the six patients (32%) with biopsy-confirmed AMR, left ventricular ejection fraction (LVEF) decreased in five (83%) and cardiac index (CI) decreased in three (50%). Conversely, LVEF increased in 91% and CI increased in 70% of biopsy-negative patients. All six AMR patients were readmitted during treatment, four for confirmed or suspected rejection. IVIg infusions may stabilize the allograft in patients with elevated DSA and negative biopsies, but once AMR has developed does not appear to improve allograft function despite decreasing DSA levels.

A reappraisal of the pharmacologic management of gastrointestinal bleeding in patients with continuous flow left ventricular assist devices.

Advancements in the design and functionality of continuous flow left ventricular assist devices (CF-LVADs), as well as a limited number of donor hearts, have resulted in an increased utilization of this therapy among advanced heart failure (HF) patients. Despite these advancements, gastrointestinal bleeding (GIB) remains a common complication after CF-LVAD implantation. The mechanism of GIB in these patients is complex and includes a combination of angiodysplasia, platelet dysfunction, acquired von Willebrand disease, and a variety of patient-specific factors including advanced age and history of GIB. Several pharmacotherapy options have been reported in the literature, though studies supporting the use of these agents are often small, retrospective reports. Within this review, we discuss the various pharmacologic agents, their proposed mechanisms of action, and the available literature pertaining to their effectiveness and tolerability. Additionally, we propose an evidence-based treatment algorithm, encompassing the updated literature, cost of therapy, medication side effects, and ease of administration.

Less bleeding associated with apixaban versus other direct acting oral anticoagulation in solid organ transplant recipients.

BACKGROUND: The purpose of this study was to evaluate outcomes of bleeding and thrombosis resulting from the use of direct oral anticoagulants (DOACs) in a large cohort of solid organ transplant (SOT) recipients. METHODS: This was a single center, retrospective cohort study of adult kidney, heart, lung, and liver transplant recipients transplanted between August 2009 and May 2018. Patients were stratified into two groups: those who received apixaban (apixaban group) or those patients receiving either rivaroxaban or dabigatran (non-apixaban group). The primary endpoint was the cumulative incidence of bleeding while receiving DOAC therapy. The secondary endpoints were incidence of major bleeding and thrombosis at any time while receiving DOAC therapy. RESULTS: A total of 106 patients were included; 70 patients received apixaban and 36 patients received non-apixaban anticoagulation. Cumulative incidence of any bleeding was lower in the apixaban group compared to the non-apixaban group at both 90 days (4.9% vs. 16.1%) and 180 days (11.4% vs. 24.9%, P = .034). Cumulative incidence of major bleeding (P = .686) and thrombosis (P = .515) were similar between groups. DOAC dosing congruent with the package insert(s) was associated with a lower risk of thrombosis. CONCLUSION: Apixaban-based anticoagulation was associated with a lower cumulative incidence of any bleeding compared to non-apixaban DOACs.

Safety and Efficacy of a Percutaneously Inserted Ventricular Support Device Purge Solution Heparin 25 U/mL.

BACKGROUND: The Impella is a percutaneous ventricular assist device (pVAD) that provides temporary hemodynamic support to patients with cardiogenic shock or for protected percutaneous coronary intervention. The manufacturer recommends a 50-U/mL concentration of heparin purge solution (or 25 U/mL as an alternative), with systemic heparin to maintain therapeutic anticoagulation during device support. Concomitant use of systemic heparin with the purge solution may increase the risk of bleeding. OBJECTIVES: The primary objective of this study was to describe the prevalence of thrombosis and bleeding using a less-concentrated heparin purge solution (25 U/mL) in combination with systemic heparin therapy. METHODS: This was a retrospective observational cohort study of patients who required at least 12 hours of pVAD support and received 25-U/mL concentration of heparin purge solution between January 1, 2014, and May 31, 2017. The primary end points were the rate of thrombotic and bleeding events. Secondary end points included the percentage of time within the therapeutic activated partial thromboplastin time (aPTT) range. Descriptive statistics were utilized for data analysis. RESULTS: Of the 161 patients screened, 100 met inclusion criteria; 63% of patients experienced a bleeding event, with Bleeding Academic Research Consortium (BARC) type 3a being the most common. Median percentages of subtherapeutic and supratherapeutic aPTT values were similar between the bleeding and nonbleeding groups. Two patients experienced thrombotic events. CONCLUSION AND RELEVANCE: Based on our findings, the device thrombosis rate was 2% and the rate of major bleeding (BARC 3a and higher) was 35%. This study provides descriptive outcomes data of a lower-concentration heparin purge solution.

Discontinuing amiodarone treatment prior to heart transplantation lowers incidence of severe primary graft dysfunction.

BACKGROUND: Recent studies have shown an increased incidence of primary graft dysfunction (PGD) in patients treated with amiodarone prior to orthotopic heart transplant (OHT). We hypothesized that discontinuation of amiodarone before OHT may lower the incidence of severe PGD. METHODS: This was a single-center retrospective study of 381 adult OHT recipients between January 2010 and June 2017. Within 6 months prior to OHT, 197 did not receive amiodarone (Group 1), 142 continued amiodarone to OHT (Group 2), and 42 had amiodarone treatment discontinued before OHT (Group 3). RESULTS: 53 (13.9%) participants developed severe PGD, 13 (6.6%) of which were in Group 1, 36 (25.4%) were in Group 2, and 4 (9.5%) were in Group 3 (P < .001). Multivariable analysis revealed continued amiodarone treatment to OHT (Group 2; OR, 3.70; 95% CI, 1.26-10.88; P = .018) to be an independent risk factor for the development of severe PGD when Group 1 served as the reference group. Moreover, patients in Group 3 had no difference in the risk of severe PGD (OR = 0.416, 95% CI = 0.08-2.15; P = .296). CONCLUSION: We found that discontinuing amiodarone treatment prior to OHT resulted a lower incidence of severe PGD.

Survey of Anticoagulation Practices with the Impella Percutaneous Ventricular Assist Device at High-Volume Centers.

OBJECTIVES: To characterize anticoagulation practices with the Impella percutaneous ventricular assist device (pVAD). BACKGROUND: Managing anticoagulation in patients being supported by the Impella pVAD is made challenging by several unique features of the device. These include the release of a dextrose-based purge solution containing unfractionated heparin (UFH), the need to concurrently administer systemic anticoagulation with intravenous UFH, and the lack of an alternative strategy in patients with contraindications to UFH. METHODS: To characterize anticoagulation practices with the Impella pVAD, we conducted a survey of centers in the United States performing a high volume of Impella cases, which we defined as > 1 per month. Centers were contacted via email or phone and individuals who agreed to participate were provided with a link to complete the survey online. The primary measures of interest were variations in practice across centers and variations from the manufacturer's recommendations. RESULTS: Practices varied considerably among respondents (65 of 182 centers, or 35.7%) and often diverged from manufacturer recommendations. Approximately half of centers (52.4%) reported using a UFH concentration of 50 units/mL in the purge solution, whereas most of the remaining centers (41.3%) reported using lower concentrations. Strategies for the initiation and adjustment of systemic therapy also varied, as did practices for routinely monitoring for hemolysis. Nearly one-fifth of centers (16.7%) had not developed an alternative strategy for the purge solution in patients with contraindications to UFH. Most centers (58.4%) reported using argatroban or bivalirudin in this scenario, a strategy that diverges from the manufacturer's recommendations. CONCLUSIONS: Given these findings, studies to determine a systematic approach to anticoagulation with the Impella device are warranted.

Management of primary graft failure after heart transplantation: Preoperative risks, perioperative events, and postoperative decisions.

Primary graft failure (PGF) after heart transplantation (HT) is a devastating and unexpected event characterized by failure of the graft to adequately support recipient circulation necessitating high doses of vasopressors and inotropes and/or temporary mechanical circulatory support. Although it represents an increasingly common event in the current era, there remains a high degree of variability in prevalence, reported risk factors, and approach to this clinical entity. The purpose of the current review is to highlight preoperative considerations including known incidence and risk factors, perioperative issues involving the identification and management of PGF, and postoperative decisions related to weaning of mechanical circulatory support and titration of immunosuppressive therapy. Lastly, we highlight future directions in PGF research, involving basic and translational research, that have the potential to uncover novel strategies of risk stratification and treatment. CASE: Our patient is a 53-year-old man with end-stage non-ischemic dilated cardiomyopathy complicated by ventricular tachycardia (VT), post-capillary pulmonary hypertension, and renal insufficiency. After progressing to NYHA Class IV symptoms, he underwent implantation of a durable left ventricular assist device (LVAD) as bridge to transplant (BTT). On device support, he developed recurrent VT resulting in multiple defibrillator discharges and hospital admission for intravenous anti-arrhythmic therapy. He is subsequently upgraded to a higher status on the waiting list. A suitable donor is identified, with an appropriate predicted heart mass and an anticipated ischemic time of <4 hours. He is taken to the operating room, where at the time of anesthesia induction he develops vasodilatory shock, requiring high-dose vasopressors, and cardiopulmonary bypass (CPB) support for dissection. After surgical anastomosis, cross clamp removal and reperfusion, graft function is extremely poor, there is significant bradycardia requiring pacing, and the patient is unable to be weaned successfully from CPB. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is initiated, and the patient is transferred to the intensive care unit. Retrospective flow crossmatch is negative. This patient is suffering from severe primary graft failure.

Engineering a Brighter Future: The Evolving Role of the Pharmacist in the Era of the HeartMate 3.

Continuous-flow left-ventricular assist devices (CF-LVADs) are an option for patients with end-stage heart failure requiring durable mechanical circulatory support. Two of the older-generation CF-LVADs have been associated with multiple device-related complications, including bleeding and thrombosis. The newest generation CF-LVAD, the HeartMate 3, was engineered specifically to prevent device-related thrombosis. As more data enhance our understanding of the burden of bleeding and thrombotic adverse events, patients with durable mechanical circulatory support may require less-aggressive antithrombotic therapy.

Meta-Analysis of Time in Therapeutic Range in Continuous-Flow Left Ventricular Assist Device Patients Receiving Warfarin.

Continuous-flow left ventricular assist devices (CF-LVADs) prolong survival in advanced heart failure patients. Anticoagulation control is critical in CF-LVAD patients due to increased thromboembolic and bleeding risk. We assessed the quality of INR control in CF-LVAD patients measured by time in therapeutic range (TTR). We performed a systematic literature search of MEDLINE and SCOPUS through July 2017 to identify studies evaluating TTR in anticoagulated adult CF-LVAD patients. Data on key characteristics and the TTR end point were then extracted from each study by two investigators using a standardized tool. Using a Hartung-Knapp random effects model, a weighted mean TTR estimate with accompanying 95% confidence interval (CI) was calculated. Statistical heterogeneity was estimated using the I2 statistic. Five published studies were included. All studies were single-center, retrospective investigations that calculated TTR using the Rosendaal method. Sample sizes ranged from 11 to 115 patients (total of 270 patients) with durations of follow-up ranging from 9 to 76 person-years. On meta-analysis, CF-LVAD patients had a weighted mean TTR of 46.6% (95% CI: 36.0-57.3%, I2 = 94%). This suggests that warfarin is difficult to manage in CF-LVAD patients, which may contribute to high rates of bleeding and thromboembolic complications.

Heart Failure Therapy in 2016: SHIFTing the PARADIGM From Antiquated Therapies Toward Novel Agents.

Heart failure (HF) continues to afflict millions of Americans, resulting in substantial clinical and economic burden to our society. Recent literature has highlighted the role of 2 novel therapies (an angiotensin receptor blocker/neprilysin inhibitor and ivabradine) in further reducing residual disease in HF. Simultaneously, evidence has mounted suggesting that older therapies like digoxin are not effective in contemporary practice and, in fact, may be harmful. This editorial summarizes the most recently published articles pertaining to both new and old HF therapies and provides a call to action to pharmacists on how to shift patients toward effective drug regimens.

Impact of pre-implant amiodarone exposure on outcomes in cardiac transplant recipients.

Amiodarone remains one of the preferred antiarrhythmic medications for patients with advanced heart failure awaiting cardiac transplant. However, the long half-life and rapid redistribution of this agent into donor myocardium expose heart transplant recipients to potential adverse outcomes. In reviewing the current body of literature, we found that pre-operative amiodarone exposure can increase the risk of bradycardia post-transplant; however, this is unlikely to require permanent pacemaker implant. Further, amiodarone has several serious drug-drug interactions with calcineurin inhibitors. Clinicians should therefore consider empiric reduction in initial dosing for tacrolimus or cyclosporine, and carefully monitor blood levels for at least 3 months post-transplant. Although the evidence is conflicting, amiodarone exposure pre-operatively may increase the risk of early graft failure and mortality. Amiodarone use should be minimized whenever possible; if amiodarone cannot practically be discontinued in the pre-transplant phase, judicious monitoring for QTc prolongation and ventricular arrhythmia should be implemented after transplant. As most of the studies included in this review suffered from small sample sizes and limited follow-up, additional research in this area is warranted.