Cardiac Allograft Vasculopathy Research Articles

Cardiac implantable electronic devices following orthotopic heart transplantation: insights on indications and outcomes from a single centre experience

Abstract Background Need for cardiac implantable electronic devices (CIED) after orthotopic heart transplantation (OHT) ranges from 7 to 24% of cases depending on several patient and procedural related factors. Purpose The aims of this study were to investigate the frequency, indications and the predictors of CIED implantation (especially permanent pacemaker [PPM]) following biatrial anastomosis OHT. Methods A retrospective, single centre, observational study was conducted, including all the patients who underwent OHT between May 1990 and October 2023 at our Institution. For each patient clinical and procedural information were collected and a long-term active follow-up was performed. The primary endpoint of the study was PPM or implantable cardioverter defibrillator (ICD) implantation while all-cause mortality or de novo OHT was a secondary endpoint. Uni- and multivariable logistic regression analyses were performed to identify factors associated with PPM implantation. Results Overall, 546 patients were included and followed-up for a median of 8 years [IQR 1.2-14.3]. During this time frame, 89 (16.3%) patients required PPM implantation (only one patient [0.2%] underwent ICD implantation) at median time of 110 days [IQR 25-2230] after OHT. The main indication for PPM implantation was the development of sinus node dysfunction in 60 patients (67.4%) whereas 29 (32.6%) patients with atrioventricular block required PPM implantation. During follow-up, 265 deaths (48.5%) occurred but no significant differences in long-term prognosis were observed between patients requiring CIED implantation and those who did not (45.5% vs. 49.1%, p-value=0.53, figure). At multivariable analysis, impaired renal function (i.e. low eGFR), cardiac allograft vasculopathy, the occurrence of severe heart transplant rejection and a higher BMI were factors associated with PPM implantation (table). Conclusions Among patients undergoing OHT with biatrial anastomosis technique, PPM implantation is not uncommon but it does not negatively impact on prognosis. Several factors, especially severe heart transplant rejection, cardiac allograft vasculopathy and impaired renal function can help identifying patients at higher risk of PPM.TableFigure

Non-invasive myocardial tissue deformation and discoordination indices predict cardiac allograft vasculopathy in pediatric heart transplantation patients.

There is an urgent need for non-invasive imaging-based biomarkers suitable for diagnostic surveillance of cardiac allograft vasculopathy (CAV) in pediatric heart transplant (PHT) patients. The purpose of this study was to comprehensively investigate left ventricular (LV) myocardial deformation in conjunction with electromechanical discoordination in PHT. PHT patients with and without CAV were evaluated for echocardiography derived global longitudinal strain (GLS) and electromechanical discoordination indices including systolic stretch fraction (SSF) and diastolic relaxation fraction (DRF). SSF was increased in CAV(+) patients at the time of CAV diagnosis (median CAV(+) 5.0 vs. median CAV(-) 0.0, P = 0.008) and in the echocardiogram preceding the CAV diagnosis (median CAV(+) 29.0 vs. median CAV(-) 0.0, P < 0.001). DRF was also increased in the echocardiogram that preceded CAV diagnosis in CAV(+) patients (0.31 ± 0.08 vs. 0.25 ± 0.05, P = 0.008). The final model using indices 6-12 months prior to CAV diagnosis included GLS, SSF, and DRF providing AUC of 0.94 with sensitivity 98.5%, specificity 80.0%, positive predictive value 85.0%, and negative predictive value 94.1%. Systolic and diastolic electro-mechanical discoordination indices are significantly worse in PHT patients experiencing CAV. Non-invasive imaging guided surveillance using echocardiographic myocardial deformation indices can be improved by adding SSF and DRF to standard GLS measurements.

Echocardiography to predict left ventricular filling pressure for long-term paediatric heart transplant patients.

Left ventricular diastolic dysfunction is a recognised sequela following transplantation in paediatric heart transplant patients. Traditional echocardiographic indices do not correlate well with left ventricular filling pressure immediately after transplantation. This study aimed to assess whether these indices have any long-term correlation after transplantation in paediatric patients. A retrospective chart review of 41 patients who had a heart transplant before the age of 24 years was performed. The median time since the transplantation was 11 years. Data obtained from surveillance cardiac catheterisation and echocardiographic examination were reviewed. Traditional echocardiographic indices of diastolic function were compared with the pulmonary capillary wedge pressure and left ventricular end-diastolic pressure obtained from cardiac catheterisation. The median age at transplant was 12.1 years, and the median time since transplant was 11 years. Eighteen patients (43%) had a history of at least one rejection episode and 12 patients (29%) had a history of cardiac allograft vasculopathy. There was no correlation between mitral inflow E velocity, mitral E/A ratio, tissue Doppler velocities, mitral E/e' (mitral inflow E velocity to mitral annular velocity), and elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. There was no correlation between mitral valve deceleration time or isovolumetric relaxation time with elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. Our findings suggest that traditional echocardiographic indices of diastolic function do not correlate well with elevated invasive pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure in paediatric heart transplant patients' long-term post-transplantation.

Proteomics early after heart transplantation and relation to coronary intimal changes and prognosis - an exploratory study

BackgroundLong-term survival after heart transplantation (HTx) is limited by cardiac allograft vasculopathy (CAV). The pathogenesis of CAV is poorly understood, and treatment has not yet been well-established. In this exploratory study, we aimed to identify novel immune and non-immune biomarkers correlated to CAV development, and biomarkers predicting CAV related events. MethodsUsing a proteomic panel, 92 cardiovascular disease-related proteins were evaluated in 26 de novo HTx patients at 3- and 12-months post transplantation. Intima area changes were assessed using optical coherence tomography (OCT). Major adverse cardiac events (MACE) included significant CAV progression, heart failure, and cardiovascular death. ResultsMedian follow up was 6.8 years. We found changes in four inflammatory biomarkers: Matrix metalloproteinase 3 (MMP-3) and matrix metalloproteinase 2 (MMP-2) were significantly increased after 3 months in the group of patients with highest intima proliferation, and after 12 months in patients experiencing MACE, respectively. Monocyte chemotactic protein 1 (MCP-1) was increased after 12 months in patients experiencing MACE. Platelet derived growth factor subunit A (PDGF-A) was significantly increased after 3 months in the group of patients with highest intima proliferation. ConclusionsWe identified four biomarkers that may be associated with CAV development which differed significantly between groups of intima proliferation and MACE; MMP-2, MMP-3, MCP-1 and PDGF-A. Further studies are needed to examine whether our findings offer the basis to seek for new markers of graft vasculopathy or treatment options.

Utility of 64-Slice Coronary Computed Tomography Angiography in Heart Transplant Recipients

Graft vasculopathy is a leading cause of death after heart transplantation (HTx). Diagnosing cardiac allograft vasculopathy (CAV) within this patient group poses significant challenges. This study aimed to evaluate the safety and efficacy of coronary computed tomographic angiography (CCTA) in patients after HTx. We enrolled 107 consecutive HTx recipients (26 women, mean age 50 ± 17 years); all were ≥3 years post-HTx with minimal or no evidence of CAV in a prior coronary angiography performed a minimum of 2 years before the current examination. The inclusion criteria comprised an estimated glomerular filtration rate (eGFR) of ≥30, absence of new heart failure symptoms, and no contraindications to iodine contrast or CT scans. All patients underwent a 64-slice CCTA. In cases of minimal or no changes, noninvasive follow-up examinations were conducted. Significant changes in CT prompted additional coronary angiography. Of the enrolled participants, 9 exhibited minimal changes; 98 displayed no changes in coronary angiography. The median time since transplant was 7 years, with IQR of 4 to 11.25 years. Significant changes were excluded in 98 patients. Among the 9 patients with suspected significant CAV, significant changes were confirmed in 8 patients, resulting in percutaneous transluminal coronary angioplasty (PTCA) performed in 6. One patient from this group died shortly after PTCA. No cardiovascular incidents were observed within the remaining group. The median follow-up period was 539 (IQR = 289-654 days). The mean left ventricular ejection fraction at follow-up was 58% ± 5% compared with 58% ± 4% at baseline. At follow-up, the mean eGFR was 64 ± 18 mL/kg/1.73 m2 compared with the baseline value of 67.2 mL/kg/1.73 m2. CCTA appears to offer a secure and efficient means of assessment in HTx recipients.

Impact of Everolimus Initiation and Corticosteroid Weaning During Acute Phase After Heart Transplantation on Clinical Outcome: Data from the Korean Organ Transplant Registry (KOTRY).

The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56years (interquartile range [IQR], 45-62), and the median follow-up time was 3.9years (IQR 2.0-5.1). The early EVR initiation within the first year post-HTx and maintenance during the follow-up is associated with reduced the risk of primary composite outcome (all-cause mortality or re-transplantation) (HR, 0.24; 95% CI 0.09-0.68; p < 0.001) and cardiac allograft vasculopathy (CAV) (HR, 0.39; 95% CI 0.19-0.79; p = 0.009) compared with EVR-free or EVR intermittent treatment regimen, regardless of CS weaning. However, the early EVR initiation tends to increase the risk of acute allograft rejection compared with EVR-free or EVR intermittent treatment.

(387) - Circulating Progenitor Cells, Cardiac Allograft Vasculopathy, and Outcomes in Heart Transplant

(387) - Circulating Progenitor Cells, Cardiac Allograft Vasculopathy, and Outcomes in Heart Transplant

Right Ventricular Function on Cardiovascular Magnetic Resonance Imaging and Long-Term Outcomes in Stable Heart Transplant Recipients.

In heart transplant recipients, right ventricular (RV) dysfunction may occur for a variety of reasons. Whether RV dysfunction in the stable phase after heart transplantation is associated with long-term adverse outcomes is unknown. We aimed to determine the long-term prognostic significance of RV dysfunction identified on cardiovascular magnetic resonance imaging (CMR) at least 1 year after heart transplantation. In consecutive heart transplant recipients who underwent CMR for surveillance, we assessed 2 CMR measures of RV function: RV ejection fraction and RV global longitudinal strain (RVGLS). We investigated associations between RV dysfunction and a composite end point of death or major adverse cardiac events, including retransplantation, nonfatal myocardial infarction, coronary revascularization, and heart failure hospitalization. A total of 257 heart transplant recipients (median age, 59 years; 75% men) who had CMR at a median of 4.3 years after heart transplantation were included. Over a median follow-up of 4.4 years after the CMR, 108 recipients experienced death or major adverse cardiac events. In a multivariable Cox regression analysis adjusted for age, time since transplantation, indication for transplantation, cardiac allograft vasculopathy, history of rejection, and CMR covariates, RV ejection fraction was not associated with the composite end point, but RVGLS was independently associated with the composite end point with a hazard ratio of 1.08 per 1% worsening in RVGLS ([95% CI, 1.00-1.17]; P=0.046). RVGLS provided incremental prognostic value over other variables in multivariable analyses. The association was replicated in subgroups of recipients with normal RV ejection fraction and recipients with late gadolinium enhancement imaging. A similar association was seen with a composite end point of cardiovascular death or major adverse cardiac events. CMR feature tracking-derived RVGLS assessed at least 1 year after heart transplantation was independently associated with the long-term risk of death or major adverse cardiac events. Future studies should investigate its role in guiding clinical decision-making in heart transplant recipients.

(182) - Waitlist Mortality for Patients with Cardiac Allograft Vasculopathy Under the 2018 UNOS Donor Heart Allocation System

(182) - Waitlist Mortality for Patients with Cardiac Allograft Vasculopathy Under the 2018 UNOS Donor Heart Allocation System

(1391) - The Impact of Statin Intensity on Early Progression of Cardiac Allograft Vasculopathy

(1391) - The Impact of Statin Intensity on Early Progression of Cardiac Allograft Vasculopathy

(386) - Lower Platelet Count Following Induction with Antithymocyte Globulin is Associated with a Lower Incidence of Cardiac Allograft Vasculopathy

(386) - Lower Platelet Count Following Induction with Antithymocyte Globulin is Associated with a Lower Incidence of Cardiac Allograft Vasculopathy

Cardiac allograft vasculopathy in heart transplant recipients from hepatitis C viremic donors.

Recent studies suggest the transplantation of Hepatitis C (HCV) hearts from viremic donors is associated with comparable 1 year survival to nonviremic donors. Though HCV viremia is a known risk factor for accelerated atherosclerosis, data on cardiac allograft vasculopathy (CAV) outcomes are limited. We compared the incidence of CAV in heart transplant recipients from HCV viremic donors (nucleic acid amplification test positive; NAT+) compared to non-HCV infected donors (NAT-). We retrospectively reviewed annual coronary angiograms with intravascular ultrasound from April 2017 to August 2020 at two large cardiac transplant centers. CAV was graded according to ISHLT guidelines. Maximal intimal thickness (MIT) ≥ 0.5mm was considered significant for subclinical disease. Among 270 heart transplant recipients (mean age 54; 77% male), 62 patients were transplanted from NAT+ donors. CAV ≥ grade 1 was present in 8.8% of the NAT+ versus 16.8% of the NAT- group at 1 year, 20%versus 28.8% at 2 years, and 33.3%versus 41.5% at 3 years. After adjusting for donor age, donor smoking history, recipient BMI, recipient, hypertension, and recipient diabetes, NAT+ status did not confer increased risk of CAV (HR.80; 95% CI.45-1.40, p=0.43) or subclinical IVUS disease (HR.87; 95% CI.58-1.30, p=0.49). Additionally, there was no difference in the presence of rapidly progressive lesions on IVUS. Our data show that NAT+ donors conferred no increased risk for early CAV or subclinical IVUS disease following transplantation in a cohort of heart transplant patients who were treated for HCV, suggesting the short-term safety of this strategy to maximize the pool of available donor hearts.

Cardiac Allograft Vasculopathy: Challenges and Advances in Invasive and Non-Invasive Diagnostic Modalities.

Cardiac allograft vasculopathy (CAV) is a distinct form of coronary artery disease that represents a major cause of death beyond the first year after heart transplantation. The pathophysiology of CAV is still not completely elucidated; it involves progressive circumferential wall thickening of both the epicardial and intramyocardial coronary arteries. Coronary angiography is still considered the gold-standard test for the diagnosis of CAV, and intravascular ultrasound (IVUS) can detect early intimal thickening with improved sensitivity. However, these tests are invasive and are unable to visualize and evaluate coronary microcirculation. Increasing evidence for non-invasive surveillance techniques assessing both epicardial and microvascular components of CAV may help improve early detection. These include computed tomography coronary angiography (CTCA), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and vasodilator stress myocardial contrast echocardiography perfusion imaging. This review summarizes the current state of diagnostic modalities and their utility and prognostic value for CAV and also evaluates emerging tools that may improve the early detection of this complex disease.

Identification of Preoperative Risk Factors for the Development of Cardiac Allograft Vasculopathy: A Systematic Review

Identification of Preoperative Risk Factors for the Development of Cardiac Allograft Vasculopathy: A Systematic Review

Routine screening for HLA Antibodies in Heart Transplant patients-Does it affect clinical decision making?

We aimed to assess outcomes in patients with and without donor specific antibodies (DSA) and to evaluate the relationship between DSA presence and graft function, cardiac allograft vasculopathy (CAV), and mortality. The study population comprises 193 consecutive long-term heart transplanted (HTx) patients who underwent DSA surveillance between 2016 and 2022. The patients were prospectively screened for CAV through serial coronary angiograms, graft function impairment through serial echocardiograms, and cardiac biomarkers. The patients were followed from the first DSA measurement until death, 5 years follow-up or right censuring on the 30th of June 2023. DSAs were detected in 50 patients using a cut-off at MFI ≥1000 and 45 patients using a cut-off at ≥2000 MFI. The median time since HTx was 9.0 years [3.0-14.4]. DSA positive patients had poorer graft function and higher values of NT-proBNP and troponin T, and more prevalent CAV than DSA negative patients. In total, 25 patients underwent endomyocardial biopsies due to DSA presence while another eight patients underwent endomyocardial biopsies for other reasons. Histological antibody mediated rejection (AMR) signs were seen in three biopsies. During a median follow-up of five years [4.7-5], a total of 41 patients died. Mortality rates did not differ between DSA positive and DSA negative patients (HR 1.2, 95% CI.6-2.4). DSA positive patients were more likely to experience CAV progression than DSA negative patients (HR 2.7, 95% CI 1.5-4.8) CONCLUSIONS: Routine screening reveals DSA in approximately 25% of long-term HTx patients but is rarely related to histopathological AMR signs. DSA presence was associated with poorer graft function and more prevalent and progressive CAV. However, DSA positive patients had similar survival rates to DSA negative patients.

MTor-inhibition within the first days after pediatric heart transplantation is a potentially safe option to prevent cardiac allograft vasculopathy.

Immunosuppression after heart transplantation (HTX) with mammalian target of rapamycin (mTOR) inhibitors serves as a prophylaxis against rejection and to treat coronary vascular injury. However, there is little data on the early, preventive use of everolimus after pediatric HTX. Retrospective study of 61 pediatric HTX patients (48 cardiomyopathy and 13 congenital heart disease), 28 females, median age 10.1 (range 0.1-17.9) years transplanted between 2008 and 2020. We analyzed survival, rejection, renal function, occurrence of lymphoproliferative disorder, and allograft vasculopathy together with adverse effects of early everolimus therapy combined with low-dose calcineurin inhibitors. Everolimus therapy was started at a median 3.9 (1-14) days after HTX. Median follow-up was 4.3 (range 0.5-11.8) years, cumulative 184 patient years. The estimated 1- and 5-year survival probability was 89% (CI 82%:98%) and 87% (CI 78%:97%). Four patients developed rejection (6.6%) (maximum 2R ISHLT criteria). No patient suffered from chronic renal failure. Three patients (4.9%) developed post-transplant lymphoproliferative disorder. Five patients suffered relevant wound-healing disorders after transplantation, four of them carrying relevant risk factors before HTX (mechanical circulatory support (n = 3), delayed chest closure after HTX (n = 3)). No recipient developed cardiac allograft vasculopathy. Initiating everolimus within the first 14 days after HTX seems to be well tolerated, enabling a low incidence of rejection, post-transplant lymphoproliferative disorders, renal failure, and reveals no evidence of cardiac allograft vasculopathy as well as good overall survival in pediatric heart transplant recipients.

Acetylsalicylic acid use and development of cardiac allograft vasculopathy: A national prospective study using highly automated 3-D optical coherence tomography analysis.

There is conflicting evidence on the role of acetylsalicylic acid (ASA) use in the development of cardiac allograft vasculopathy (CAV). A nationwide prospective two-center study investigated changes in the coronary artery vasculature by highly automated 3-D optical coherence tomography (OCT) analysis at 1 month and 12 months after heart transplant (HTx). The influence of ASA use on coronary artery microvascular changes was analyzed in the overall study cohort and after propensity score matching for selected clinical CAV risk factors. In total, 175 patients (mean age 52±12 years, 79% male) were recruited. During the 1-year follow-up, both intimal and media thickness progressed, with ASA having no effect on its progression. However, detailed OCT analysis revealed that ASA use was associated with a lower increase in lipid plaque (LP) burden (p=.013), while it did not affect the other observed pathologies. Propensity score matching of 120 patients (60 patient pairs) showed similar results, with ASA use associated with lower progression of LPs (p=.002), while having no impact on layered fibrotic plaque (p=.224), calcification (p=.231), macrophage infiltration (p=.197), or the absolute coronary artery risk score (p=.277). According to Kaplan-Meier analysis, ASA use was not associated with a significant difference in survival (p=.699) CONCLUSION: This study showed a benefit of early ASA use after HTx on LP progression. However, ASA use did not have any impact on the progression of other OCT-observed pathologies or long-term survival.

Role of HLA matching and donor specific antibody development in long-term survival, acute rejection and cardiac allograft vasculopathy

Although there are different data supporting benefits of HLA matching in kidney transplantation, its role in heart transplantation is still unclear. HLA mismatch (MM) between donor and recipient can lead to the development of donor-specific antibodies (DSA) which produces negative events on the outcome of heart transplantation. Moreover, DSAs are involved in the development of antibody-mediated rejection (AMR) and are associated with an increase in cardiac allograft vasculopathy (CAV). In this study it is analyzed retrospectively the influence of HLA matching and anti-HLA antibodies on overall survival, AMR and CAV in heart transplantation. For this retrospective study are recruited heart transplanted patients at the Cardiac Transplantation Centre of Naples between 2000 and 2019. Among the 155 heart transplant patients, the mean number of HLA-A, B, -DR MM (0 to 6) between donor and recipient was 4.5 ± 1.1. The results show a negative association between MM HLA-DR and survival (p = 0.01). Comparison of patients with 0–1 MM at each locus to all others with 2 MM, for both HLA class I and class II, has not showed significant differences in the development of CAV. Our analysis detected DSA in 38.1% of patients. The production of de novo DSA reveals that there is not an influence on survival (p = 0.72) and/or AMR (p = 0.39). Instead, there is an association between the production of DSA class II and the probability of CAV development (p = 0.03). Mean fluorescence intensity (MFI) values were significantly higher in CAV-positive patients that CAV-negative patients (p = 0.02). Prospective studies are needed to evaluate HLA class II matching as an additional parameter for heart allocation, especially considering the increment of waiting list time.

Screening of cardiac allograft vasculopathy in heart transplant patients with coronary computed tomography angiography.

Although coronary angiography (CA) is the gold standard for coronary allograft vasculopathy (CAV) screening, non-invasive modalities have arisen as potential alternatives, such as coronary computed tomography angiography (CCTA). CCTA also quantifies plaque burden, which may influence medical treatment. From January 2021 to April 2022, we prospectively included heart transplant recipients who performed CCTA as a first-line method for CAV detection in a single center. Clinical, CCTA, and CA data were collected. 38 patients were included, 60.5% men, aged 58±14 years. The most frequent cause of transplantation was dilated cardiomyopathy (42.1%), and the median graft duration was 10 years [interquartile range (IQR) 9]. The median left ventricle ejection fraction was 61.5% (IQR 6). The median calcium score was 17 (IQR 231) and 32 patients (84.2%) proceeded to CCTA: 7, 24, and 1 patients had a graded CAV of 0, 1, and 2, respectively. Most patients (37.5%) had both calcified and non-calcified plaques, and the median number of affected segments was 2 (IQR 3). The remaining six patients had extensive coronary calcification, so CA was performed: 4 had CAV1, 1 had CAV2, and 1 had CAV3. During follow-up (12.2±4.2 months), there were neither deaths nor acute coronary syndromes. After CCTA, therapeutic changes occurred in about 10 (26.3%) of patients, mainly related to anti-lipid intensification; such changes were more frequent in patients with diabetes after heart transplant. In this cohort, CCTA led to therapeutic changes in about one-quarter of patients; more studies are needed to assess how CCT may guide therapy according to plaque burden.

Three-year outcomes of de novo tacrolimus extended-release tablets (LCPT) compared to twice-daily tacrolimus in adult heart transplantation

BackgroundExtended-release tacrolimus for prophylaxis of allograft rejection in heart transplant (HT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release (IR-) tacrolimus. We compared long-term efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. Methods25 prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 3 years following transplant was compared between groups using non-inferiority analysis. ResultsLCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 16% (90%CI, −37%, −1%, non-inferiority p = 0.002) up to 3 years following heart transplant. Up to 3-years post-transplant, 14 patients remained on once-daily LCPT and 10 patients were switched to IR-tacrolimus due to lack of insurance coverage. There were no significant differences in the rate of chronic kidney disease requiring dialysis, cytomegalovirus requiring treatment, cardiac allograft vasculopathy, and malignancy within 3 years following transplant. ConclusionLCPT is non-inferior in efficacy to IR-tacrolimus in heart transplantation with a similar safety profile. Narrowly-constrained FDA labels specific to kidney transplant remain a barrier to consistent access to many immunosuppressant medications for recipients of non-kidney solid organs. We recommend the FDA consider developing facile pathways for expanding the approved label of extended-release tacrolimus formulations to heart transplant recipients.