Cardiac Transplant Recipients Research Articles

Empagliflozin use in cardiac transplant patients

Objectives: Sodium-glucose transport protein 2 inhibitor |(SGLT2) drugs are used to treat patients with type 2 diabetes. In additions to their beneficial metabolic effects in lowering the glaciated hemoglobin, body weight and blood pressure, these agents have shown favorable and protective effects on the heart and the kidneys. These cardio renal benefits are seen even in people without diabetes. There is little evidence on the safety and efficacy of SGLT2 inhibitors use in cardiac transplant recipients. We wanted to study the cardiac transplant recipients who used Empagliflozin for the treatment of diabetes to evaluate its safety and efficacy in this niche sub group of patients. Method: We retrospectively identified 20 patients on the cardiac transplant recipient register taking Empagliflozin (Jardiance) or Empagliflozin combined with Metformin (Synjardy). We studied the safety and efficacy parameters. Results: Our results show improvement in HBA1c, body weight and stability in serum creatinine. There was no increased risk of genitourinary infection, hypoglycemia or diabetic ketoacidosis. Conclusion: While we need larger studies in cardiac transplant patients taking Empagliflozin, our small study provides assurance that Empagliflozin is safe to use in cardiac transplant recipients.

Clinical Recommendations for Managing Genitourinary Adverse Effects in Patients Treated with SGLT-2 Inhibitors: A Multidisciplinary Expert Consensus.

Background: SGLT-2 inhibitors (SGLT-2is) are considered to be a first-line treatment for common conditions like type 2 diabetes, chronic kidney disease, and heart failure due to their proven ability to reduce cardiovascular and renal morbidity and mortality. Despite these benefits, SGLT-2is are associated with certain adverse effects (AEs), particularly genitourinary (GU) events, which can lead to treatment discontinuation in some patients. Preventing these AEs is essential for maintaining the cardiorenal benefits of SGLT-2is. Methods: A multidisciplinary panel of experts from various medical specialties reviewed the best available evidence on GU AEs associated with SGLT-2i therapy. The panel focused on the prevention and management of genital mycotic infections, urinary tract infections, and lower urinary tract symptoms in both the general population and high-risk groups, such as renal and cardiac transplant recipients. Results: The panel found that permanent discontinuation of SGLT-2is results in a rapid loss of cardiorenal benefits. Preventive strategies, including identifying high-risk patients before initiating therapy, are critical for minimizing GU AEs. Clinical trials show that most GU infections linked to SGLT-2i therapy are mild to moderate in severity and typically respond to standard antimicrobial treatment, without the need for discontinuation. Conclusions: Routine discontinuation of SGLT-2is due to GU AEs is not recommended. Therapy should be resumed as soon as possible, unless severe or persistent conditions contraindicate their use, in order to preserve the significant benefits of SGLT-2is in reducing cardiovascular and renal events.

Endomyocardial biopsy in the diagnosis of cardiac sarcoidosis

Abstract Background Definite diagnosis of cardiac sarcoidosis (CS) requires proof of sarcoid granulomas in the heart. Endomyocardial biopsy (EMB) is considered a risky procedure with poor sensitivity (<25%) in CS (1), although comprehensive studies on its diagnostic performance are not available. Purpose We investigated the sensitivity, complications, and prognostic significance of EMB in a large cohort of patients with CS to help to choose diagnostic strategy when the disease is suspected. Methods We analysed the data of 260 consecutive patients diagnosed with CS in 1988-2022 at our institution. All met the diagnostic criteria of the Heart Rhythm Society (1). The use, findings, and complications of EMB were retrospectively noted in addition to patients’ demographics, presenting phenotype, diagnostic examinations, and future serious cardiac events. The data were retrieved from hospital records and an ongoing CS registry (2). Advanced imaging studies (cardiac magnetic resonance, positron emission tomography) were re-analysed and the follow-up information was updated until June 2023. EMB’s performance was assessed also in 30 cardiac transplant recipients having CS at the histopathologic study of the explanted heart. Results Of the 260 patients (mean age 49, 60% females), 216 (83%) underwent diagnostic EMB, 48 with repeat procedures. The sensitivity of EMB was 38%, rising to 49% after repeats. The predictors of positive EMB (Table 1) included the presenting phenotype and characteristics of the activity, extent, and location of myocardial involvement. Presentation with ventricular tachyarrhythmia, left ventricular (LV) ejection fraction ≤45%, elevation of cardiac troponins, and presence of middle or apical LV septal late gadolinium enhancement on magnetic resonance imaging were independent predictors (p<0.05) of positive biopsy. The sensitivity of EMB was directly related to the count of the predictors present (Figure 1). The rate of procedural complications was 9.7% overall and 0.7% for major events. One pericardial effusion needed drainage, but no deaths or long-term sequels followed the biopsies. Minor complications included 10 paroxysms of ventricular tachycardia and 6 small pericardial effusions. The 10-year rate (95% CI) of the composite of cardiac death, end-stage heart failure, or ventricular tachyarrhythmia was 55% (44-67%) with positive EMB vs 29% (17-44%) with negative EMB (p<0.001). When adjusted for the presenting phenotype and LV ejection fraction, EMB did not predict outcome events. In the 30 patients with CS in explanted hearts, the sensitivity of EMB, including the repeats, was 60%. Conclusion The sensitivity of EMB is better than usually presented in CS and the higher the more extensive myocardial involvement is. Risk of serious complications is <1%. In patients with suspect CS, the pre-test likelihood and value of positive EMB should be weighed against the procedural risks in shared decision-making when choosing the diagnostic pathway.

Recent cardiac rehabilitation and its impact on cardiopulmonary exercise test variables in Brazilian cardiac transplant recipients

Abstract Introduction Heart transplantation (HTx) is an option for restoring the functional capacity of individuals with end-stage heart failure (HF). Cardiac rehabilitation (CR) plays an important role in improving variables related to cardiopulmonary exercise testing (CPET) in post-HTx patients. Purpose To evaluate whether CR is effective in improving CPET variables in Brazilian patients post-recent HTx compared to a Control Group (CG). Methods Retrospective comparative study composed of two groups: CR group (CRG) and CG. These recent HTx patients (aged 14 to 73 years) initiated CR within 150 days and were recruited from an HTx outpatient clinic at a south Brazilian public university hospital between 2014 and 2023. CPET was performed at three different times: pre-HTx (Time 01), post-recent HTx (Time 02), and post-CR or post-follow-up for CG (Time 03). This study was approved by the Institutional Review Board (protocol No. 20180651). Statistical analysis used Generalized Estimating Equations with alpha ≤ 0.05, and the mean difference (MD) data were presented along with 95% confidence interval (CI). Results CRG (n=18) had a mean age of 47.3±15.6 years and CG (n=11) 48.6±12.5 years (P=0.81). The mean time to start CRG was 62.2±9.6 days (minimum: 21; maximum: 147). There was an interaction for the Group*Time factor for the following CPET variables: VO2peak (P=0.039); VEmax (P=0.009); VO2 on second ventilatory threshold (P<0.001); HR on VT2 (P=0.030) and T½ (P=0.002). The main results are summarized in Table 1. We highlight that there was a difference in the comparison between groups at Time 03 for the variable VO2peak: MD: 5.16 ± 1.95 (95% CI: 1.3 to 9.0; P = 0.008), favorable to CRG. Conclusion Early CR after very recent HTx significantly increase peak VO2peak, VEmax, T½ and VO2 and HR at the VT2 compared to the control group (CG).

Incidence of acute cellular and antibody mediated rejection in heart transplantation from a tertiary care center

Abstract Background Heart transplant greatly increases the survival in patients with end stage heart failure. However, cardiologists and cardiothoracic surgeons face difficulty in detecting rejection at times. Post-cardiac transplant surveillance biopsy remains the gold standard for diagnosing rejection and therapeutic intervention. Purpose The objective is to report our experience of monitoring rejection by endomyocardial biopsy (EMB). Methods The index study is an ambispective one where we evaluated all the patients who underwent heart transplant at our center from 1994 to 2021. Results Heart transplant were carried out in 72 patients within a period of 28 years, with majority being done after 2016. The patients mean age was 31.6 years (10-59 years). The commonest indication was dilated cardiomyopathy (67%) followed by ischemic cardiomyopathy (2.5%), congenital heart disease (7%) and other miscellaneous causes (5%). The mean age of donors was 31.8 years (14-55 years). Eight of the 72 patients died without any post cardiac transplant endomyocardial biopsy. The remaining 64 patients underwent cumulatively a total of 271 endomyocardial biopsy procedures. Majority of endomyocaridal biopsies contained three cores (range 1-7). First EMB procedure was performed in 17 (26.6%) patients within first seven days, 35(53.1%) within the second week and 12(20.3%) after 14 days. Histologically rejection was identified in 42 (66%) patients. Thirty-nine (61%) had only acute cellular rejection (ACR), one (1.6%) had only antibody mediated rejection (AMR) and two (3.1%) had mixed ACR and AMR. These 42 patients with rejection had a total of 90 (33.2%) episodes of ACR detected in 271 endomyocardial biopsies. Out of 90 ACR, 44 (48.9%) occurred in less than six months; seventeen (18.9% of 90 ACR) episodes occurred between six and 12 months and 29 (32.2%) after one year. The mean of presentation of first ACR episode was 36 weeks (range 5 days to 3.6 years). There were 172 endomyocardial procedures within one year of transplantation of which 61 (35%) showed rejection. Ninety-nine endomyocardial procedures were performed one year of transplantation of which 29 (29%) showed rejection. Most common grade in both the time period was ACR grade 1R (International Society for Heart and Lung Transplantation (ISHLT) 2004) (72.1% in ≤1 year and 65.5% in >1 year) followed by 2R and 3R. Thirty-eight (90.4%) of 42 patients expired in less than five years since transplantation. Two (4.8%) patients survived between five to ten years post transplantation and two (4.8%) survived more than ten years. The longest cardiac transplant recipient had completed 23 years since cardiac transplant and is alive till date. Conclusions EMB being the gold standard for cardiac allograft rejection, the cardiac pathologists need to be aware of the various grades of rejection including mixed rejection.Acute cellular rejection (ISHLT 2004)

Sympathetic reinnervation in cardiac transplant recipients: Prevalence, time course and association with long-term survival

BackgroundPartial cardiac sympathetic reinnervation after cardiac transplant has been extensively investigated and evidenced. However, there have been no large-scale, long-term studies evaluating the prevalence, time-course, and association with long-term survival of sympathetic reinnervation of the heart. MethodsCardiac transplant recipients (n=232) were recruited from outpatient clinic at a single transplant centre in the United Kingdom. Participants were each tested once for the presence of sympathetic reinnervation of the sinus node using the low frequency component of power spectral analysis of heart rate variability, with a cut-off defined as 2 standard deviations above the mean for denervated participants (those tested <56 days post-transplant). Time-course was calculated based on the timing of testing post-transplant. Patients were then followed-up over a period of up to 27 years after transplant for survival analysis. ResultsThe overall prevalence of cardiac sympathetic reinnervation in the 225 patients tested >56 days post-transplant was 64.9%. Sympathetic reinnervation primarily occurred in the first 18 months after transplant, with a plateau thereafter. The prevalence in participants tested >18 months post-transplant was 69.6%. In Kaplan-Meier survival analysis, sympathetic reinnervation was associated with significantly improved survival (Log-rank P=0.019), with a median survival time for reinnervated patients of 19.9 years compared to 14.4 years for the denervated group. ConclusionsSympathetic reinnervation of the sinus node occurs mostly within 18 months of transplant, is found in 70% of cardiac transplant recipients tested >18 months post-transplant, and is associated with significantly improved long-term survival.

SIGNET: protocol for a multicentre, single-blind prospective, group sequential, randomised controlled trial to evaluate the benefits of a single dose of simvastatin given to potential organ donors declared dead by neurological criteria on outcomes in organ recipients

IntroductionSuccessful organ transplantation in patients with end-stage organ failure improves long-term survival, improves quality of life and reduces costs to the NHS. Despite an increase in the number of deceased...

The pharmacokinetics of ganciclovir during prolonged intermittent kidney replacement therapy in a cardiac transplant recipient.

Ganciclovir, a guanine analogue, is used intravenously (IV) first-line for the prophylaxis and treatment of cytomegalovirus (CMV) infection in solid organ transplant recipients. The pharmacokinetics (PK) of ganciclovir are highly variable, with myelosuppression occurring at high concentrations. Ganciclovir is primarily renally excreted as the parent compound, and clearance is significantly reduced in renal impairment. Acute kidney injury (AKI) is a common post-operative complication of cardiac transplantation, reducing the clearance of ganciclovir. In the intensive care unit (ICU), AKI is often managed by kidney replacement therapy (KRT). One form of KRT, prolonged intermittent kidney replacement therapy (PIKRT) is increasingly used for cost and flexibility advantages. Ganciclovir dosing recommendations are available for varying degrees of renal impairment and KRT, except for PIKRT. In this case of cardiac transplantation, complicated by anuric AKI, a ganciclovir dose of 2.0-2.5 mg/kg of adjusted body weight given after each PIKRT session was demonstrated to achieve PK targets.

Normothermic Machine Perfusion Is Associated With Improvement in Mortality and Graft Failure in Donation After Cardiac Death Liver Transplant Recipients in the United States.

Use of normothermic machine perfusion (NMP) may help to expand the liver transplantation (LT) donor pool by potentially increasing the utilization of donation after circulatory death (DCD) organs. The aim of this study was to assess the impact of NMP on LT from DCD organs. Data among DCD adult LT recipients in the United Network for Organ Sharing between January 2016 and December 2022 were analyzed. Outcomes were compared between 2 groups: NMP versus non-MP using propensity score matching. During the study period, 4217 DCD LT recipients (NMP: 257 and non-MP: 3960) were identified. compared with non-MP, DCD LT recipients in NMP group were older (median recipient age: 61 versus 59 y, P = 0.013), had lower model for the end-stage liver disease score, longer wait time (126 versus 107 d, P = 0.028), and received organs from older donors (median age: 42 versus 38 y, P < 0.01) with longer preservation time (9.9 versus 5.3 h, P < 0.001). Two-year overall survival (NMP 94.4% versus non-MP 89.7%, P = 0.040) and 2-y graft survival (NMP 91.3% versus non-MP 84.6%, P = 0.017) were better in the NMP group. After propensity score matching, 2-y overall survival (NMP 94.2% versus non-MP 88.0%, P = 0.023) and graft survival (NMP 91.3% versus non-MP 81.6%, P = 0.004) were better in the NMP group. On multivariable cox regression analysis, NMP was an independent factor of protection against mortality (hazard ratio, 0.43; 95% confidence interval: 0.20-0.91; P = 0.029) and against graft failure (hazard ratio, 0.26; 95% confidence interval: 0.11-0.61; P = 0.002). Use of NMP for LT from DCD donors was associated with improved posttransplant patient and graft survival.

6299107 Anaesthetic, maternal and neonatal outcomes in cardiac transplant recipients

6299107 Anaesthetic, maternal and neonatal outcomes in cardiac transplant recipients

D-43 | Restenosis and Outcomes Following PCI of Small Vessels in Cardiac Transplant Recipients

D-43 | Restenosis and Outcomes Following PCI of Small Vessels in Cardiac Transplant Recipients

(971) - Kaposi Sarcoma Due to Possible Donor-Derived Human Herpesvirus-8 Infection in a Cardiac Transplant Recipient

(971) - Kaposi Sarcoma Due to Possible Donor-Derived Human Herpesvirus-8 Infection in a Cardiac Transplant Recipient

(345) - Allosensitized Cardiac Transplant Recipients Treated with CD38-Antibody Daratumumab Show Histomorphologic Signs of PAMR in Biopsies without Clinical Signs of Rejection

(345) - Allosensitized Cardiac Transplant Recipients Treated with CD38-Antibody Daratumumab Show Histomorphologic Signs of PAMR in Biopsies without Clinical Signs of Rejection

Ten-year outcomes post percutaneous coronary intervention in cardiac transplant recipients

BackgroundCardiac allograft vasculopathy (CAV) is one of the major late causes of mortality in cardiac transplant recipients beyond the first year. Given the lack of longer term data for PCI in cardiac transplant recipients, we report ten year follow up of such cardiac transplant recipients who underwent PCI at Mayo Clinic. MethodsA retrospective observational study was conducted that included cardiac transplant recipients who underwent PCI at the Mayo Clinic. Continuous variables were presented as mean (SD) or median (IQR) and discrete variables were presented as frequency (percentage). ResultsThirty-eight consecutive cardiac transplant recipients underwent PCI from January 1, 1995, to June 30, 2023, at the Mayo Clinic. The median age of the cohort was 61.00 years (IQR:51.00–70.00) comprised predominantly of men (65.80%), and 47.40% of the cohort presented with an acute coronary syndrome. The antirejection therapy prior to the PCI included steroids (47.30%), cyclosporine (26.30%), tacrolimus (15.80%), mycophenolate (42.10%), azathioprine (13.10%), & sirolimus (31.57%). Intravascular ultrasound during PCI was utilized in 10.50% of the cases. The median time duration between heart transplant and PCI was 9.00 years (IQR:6.00–13.00 years). Two individuals needed repeat heart transplant for severe CAV. In hospital mortality was 5.20% and the long-term median survival was 7.20 years with a 10-year mortality rate of 65.70%. ConclusionsThis is the first publication reporting ten-year outcomes for PCI in cardiac transplant patients. The salient features for our cohort were a 65.70% mortality rate at 10 years and a median survival of 7.20 years.

Durable immunity to EBV after rituximab and third-party LMP-specific T cells: a Children’s Oncology Group study

AbstractPosttransplant lymphoproliferative disease (PTLD) in pediatric solid organ transplant (SOT) recipients is characterized by uncontrolled proliferation of Epstein-Barr virus–infected (EBV+) B cells due to decreased immune function. This study evaluated the feasibility, safety, clinical and immunobiological outcomes in pediatric SOT recipients with PTLD treated with rituximab and third-party latent membrane protein–specific T cells (LMP-TCs). Newly diagnosed (ND) patients without complete response to rituximab and all patients with relapsed/refractory (R/R) disease received LMP-TCs. Suitable LMP-TC products were available for all eligible subjects. Thirteen of 15 patients who received LMP-TCs were treated within the prescribed 14-day time frame. LMP-TC therapy was generally well tolerated. Notable adverse events included 3 episodes of rejection in cardiac transplant recipients during LMP-TC therapy attributed to subtherapeutic immunosuppression and 1 episode of grade 3 cytokine release syndrome. Clinical outcomes were associated with disease severity. Overall response rate (ORR) after LMP-TC cycle 1 was 70% (7/10) for the ND cohort and 20% (1/5) for the R/R cohort. For all cohorts combined, the best ORR for LMP-TC cycles 1 and 2 was 53% and the 2-year overall survival was 70.7%. vβT-cell receptor sequencing showed persistence of adoptively transferred third-party LMP-TCs for up to 8 months in the ND cohort. This study establishes the feasibility of administering novel T-cell therapies in a cooperative group clinical trial and demonstrates the potential for positive outcomes without chemotherapy for ND patients with PTLD. This trial was registered at www.clinicaltrials.gov as #NCT02900976 and at the Children's Oncology Group as ANHL1522.

Induction immunosuppression and post-transplant diabetes mellitus: a propensity-matched cohort study.

Post-transplant diabetes mellitus (PTDM) is a common complication among cardiac transplant recipients, causing diabetes-related complications and death. While certain maintenance immunosuppressive drugs increase PTDM risk, it is unclear whether induction immunosuppression can do the same. Therefore, we evaluated whether induction immunosuppression with IL-2 receptor antagonists, polyclonal anti-lymphocyte antibodies, or Alemtuzumab given in the peri-transplant period is associated with PTDM. We used the Scientific Registry of Transplant Recipients database to conduct a cohort study of US adults who received cardiac transplants between January 2008-December 2018. We excluded patients with prior or multiple organ transplants and those with a history of diabetes, resulting in 17,142 recipients. We created propensity-matched cohorts (n=7,412) using predictors of induction immunosuppression and examined the association between post-transplant diabetes and induction immunosuppression by estimating hazard ratios using Cox proportional-hazards models. In the propensity-matched cohort, the average age was 52.5 (SD=13.2) years, 28.7% were female and 3,706 received induction immunosuppression. There were 867 incident cases of PTDM during 26,710 person-years of follow-up (32.5 cases/1,000 person-years). There was no association between induction immunosuppression and post-transplant diabetes (Hazard Ratio= 1.04, 95% confidence interval 0.91 - 1.19). Similarly, no associations were observed for each class of induction immunosuppression agents and post-transplant diabetes. The use of contemporary induction immunosuppression in cardiac transplant patients was not associated with post-transplant diabetes.

Comparative Analysis of Clinical Outcomes for COVID-19 and Influenza among Cardiac Transplant Recipients in the United States.

COVID-19 infections can lead to worse outcomes in an immunocompromised population with multiple comorbidities, e.g., heart transplant patients. We used the National Inpatient Sample database to compare heart transplant outcomes in patients with COVID-19 vs. influenza. A total of 2460 patients were included in this study: heart transplant with COVID-19 (n = 1155, 47.0%) and heart transplant with influenza (n = 1305, 53.0%) with the primary outcome of in-hospital mortality. In-hospital mortality (n = 120) was significantly higher for heart transplant patients infected with COVID-19 compared to those infected with influenza (9.5% vs. 0.8%, adjusted OR: 51.6 [95% CI 4.3-615.9], p = 0.002) along with significantly higher rates of mechanical ventilation, acute heart failure, ventricular arrhythmias, and higher mean total hospitalization cost compared to the influenza group. More studies are needed on the role of vaccination and treatment to improve outcomes in this vulnerable population.

Cardiac Allograft Rejection: Strategies for Success in the Face of Immune Challenges.

Heart transplantation for patients with end-stage heart failure refractory to medical therapy has remained definitive treatment with significant advances in posttransplant care. Despite improvement in postoperative morbidity and mortality, acute cellular rejection (ACR) and antibody-mediated rejection (AMR) remain substantial challenges that can lead to allograft failure and patient mortality. Immunosuppressive agents have been the mainstay of both prevention and treatment for ACR and AMR; however, many challenges exist with traditional therapies. There are a multitude of molecular pathways involved in mediating the humoral and cellular response to rejection, offering various targets for treatment. This review summarizes therapies used in the management of ACR and AMR as extrapolated from use in induction therapy and treatment of other solid-organ transplant rejection. Future studies focused on cardiac transplant recipients are needed to expand therapeutic options.

Combined Plasmapheresis and Complement Inhibition in a Highly Allosensitised Cardiac Transplant Recipient

Combined Plasmapheresis and Complement Inhibition in a Highly Allosensitised Cardiac Transplant Recipient

The COVID-19 Pandemic and Adult Cardiac Transplantation: Impact, Interventions, and Implications.

In this review, we provide a comprehensive overview of the impact of the COVID-19 pandemic on adult heart transplantation. We highlight the decline in the number of adult transplantations performed throughout the pandemic as a consequence of restrictions imposed on individual programs and hospitals. There were challenges to maintaining cardiac transplant activity at multiple levels, including organ donation in intensive care units, logistical difficulties with organ procurement, and rapidly changing resource considerations at health system and jurisdictional levels. We also review the impact of COVID-19 on cardiac transplant recipients. Despite the high rates of morbidity and mortality observed during the initial phases of the pandemic among heart transplant patients infected with COVID-19, the availability of effective vaccines, pre-exposure prophylaxis, and specific antiviral therapies have drastically improved outcomes over time. Vaccines have proven to be safe and effective in reducing infections and illness severity, but specific considerations in the immunocompromised solid organ transplant population apply, including the need for additional booster doses to achieve sufficient immunisation. We further outline the strong rationale for vaccination before transplantation wherever possible. Finally, the COVID-19 response created a number of barriers to safe and efficient post-transplantation care. Given the need for frequent evaluation and monitoring, especially in the first several months after cardiac transplantation, the pandemic provided the impetus to improve virtual care delivery and explore noninvasive rejection surveillance through gene expression profiling. We hope that lessons learned will allow us to prepare and pivot effectively during future pandemics and health care emergencies.