Heart Transplant Recipients Research Articles

A contemporary simple risk score for prediction of severe acute kidney injury after heart transplantation.

The aim of this study was to develop a simple risk score to estimate severe acute kidney injury (AKI) risk based on a large contemporary heart transplantation (HT) cohort. From 1 January 2015 to 31 December 2021, all consecutive HT recipients in our institute were included and analysed for the occurrence of AKI within the first seven postoperative days. Patients transplanted between 2015 and 2019 comprised the derivation cohort, and those transplanted between 2020 and 2021 formed the validation cohort. The primary endpoint was severe AKI (AKI stages 2-3). The impact of severe AKI on 90day mortality was also evaluated. Overall, 430 HT patients were included in the derivation cohort, and 108 were included in the validation cohort. Postoperative AKI occurred in 388 (72%) patients, including 162 (30%) severe AKI. The risk of 90day mortality significantly increased in patients with severe-AKI. Seven independent predictors of severe AKI were found in the derivation cohort, including recipients' body mass index, history of diabetes, anaemia, preoperative inotropes, estimated glomerular filtration rate, cardiopulmonary bypass duration and intraoperative red blood cell transfusion. The occurrence of severe AKI increased gradually from the lowest to the highest of the four risk score groups in the derivation and validation cohort. The scoring prediction model showed a highly acceptable discriminating power for severe-AKI [C statistic: 0.76, 95% confidence interval (CI): 0.71-0.80 for derivation cohort; C statistic: 0.79, 95% CI: 0.71-0.89 for validation cohort]. A contemporary simple risk score based on available variables from patients undergoing HT can accurately discriminate the risk of severe AKI.

Abstract 4118070: High Output Heart Failure After Leadless Pacemaker Placement In a Heart Transplant Recipient

Introduction: The advent of leadless pacemaker (LP) technology has revolutionized cardiac rhythm management by minimizing risks associated with traditional transvenous pacemakers. LP use is expected to increase as dual-chamber LP systems emerge into clinical practice. The LP requires a large-bore venous sheath (27-Fr) through a femoral vein. One risk of large bore femoral cannulation is creation of an occult arteriovenous fistula (AVF), which can cause high output heart failure (HOHF) over time. In the LEADLESS II trial, the event rate for AVF was 0.2%. HOHF as a complication of LP implant has not been previously reported. We describe the first case of HOHF in a heart transplant (HT) recipient after LP. Case Presentation: An 82-year-old male with a history of HT 26 years earlier underwent leadless pacemaker for recurrent syncope, deemed associated with conduction system disease. He had no history of cardiac allograft rejection, angiographic coronary allograft vasculopathy or left ventricular dysfunction. Six months post-implant he presented with shortness of breath and bilateral lower extremity edema. Management: Evaluation included: 1) Chest X-ray which was suggestive of pulmonary edema 2) natriuretic peptide level of 5,500 pg/ml (6-fold increase from 6 months prior) 3) echocardiogram showing EF of 69%, and 4) bilateral lower extremity Doppler ultrasound where he was found to have a large AVF between the right superficial femoral artery and superficial femoral vein. Subsequent right heart catheterization was notable for a PCWP of 18 mmHg and a cardiac output/index of 11 L/min and 5.8 L/min/m2 respectively, hence confirming HOHF. Treatment with intravenous diuretic was initiated and percutaneous stent placement to correct the AVF was performed with symptomatic relief. Conclusion: This case highlights the rare but serious complication of unrecognized AVF following leadless pacemaker implant. Given that this event occurred in a HT recipient, a more exhaustive work-up was required to rule-out expected causes of congestion. To our knowledge there is only one other case report describing AVF post-LP implant for which no intervention was performed due to absence of symptoms at 6-month follow up and HOHF was not reported. Our case emphasizes that the differential diagnosis of new onset of signs and symptoms of heart failure that develop post LP implant in general and in HT recipients specifically, should include HOHF related to an unrecognized procedural AVF.

Abstract 4136754: Psychoactive medication use in pediatric heart transplant recipients: An assessment of prevalence, risk factors, and outcomes

Background: There is increasing recognition of the mental health burden experienced by pediatric heart transplant (HTx) recipients. Mental health concerns can impact physical health and increase risk of poor health outcomes. Using the Pediatric Heart Transplant Society (PHTS) database, we assessed the use of psychoactive medications as a proxy for mental health issues. We assessed the prevalence of psychoactive medication usage, pre- and post HTx factors, and post HTx outcomes associated with psychoactive medication usage. Methods: We queried the PHTS database for patients >5 years of age at time of follow-up who underwent HTx between January 2015 and June 2023. Patients with use of any psychoactive medication were identified. Sub-analyses were performed for use of antianxiety/antidepressant and attention-deficit/hyperactivity disorder (ADHD) medications. Multivariate logistic regression models were utilized to assess risk factors and impact on outcomes, including graft survival, coronary artery vasculopathy (CAV), and rejection at 1, 3, and 5 years post-HTx. Results: Among 1792 patients older than 5 at 1 year post HTx, 301 (16.8%) were prescribed at least one psychoactive medication; 246 (13.7%) were prescribed medication for antianxiety/antidepressant medications and 59 (3.3%) for ADHD. Utilization of psychoactive medication decreased at 3 years (14.8%, N= 240 of 1629) and 5 years post HTx (11.3%, N=230 of 2029). Patients on psychoactive medications at 1 year post HTx tended to be older (OR=2.1, p<0.001), had higher priority listing status (OR=2.3, p<0.05), and longer bypass time (OR=1.6, p<0.05). Black patients were less likely to be prescribed psychoactive medication at 3-years post HTx than white patients (OR=0.57, p<0.05) or other races (OR=0.43, P <0.001). There was no association of psychoactive medication usage on graft survival, CAV, or rejection at 1 year post HTx. At 3 years post HTx psychoactive medication usage was associated with significantly higher prevalence of CAV (p<0.05). At 5 years post HTx graft loss (p<0.005) and CAV (p<0.05) were significantly increased in patients on psychoactive medications. Conclusions: A significant proportion of pediatric HTx patients take psychoactive medications. This population may be at risk for worse long-term outcomes. There is a need to assess the mental health burden of pediatric HTx and to identify modifiable factors to improve assessment and treatment of mental health issues and its impact on outcomes.

Abstract 4140154: Highly Sensitized Heart Transplant Recipients Who Have Undergone Pre-Transplant Desensitization Therapies Demonstrate Acceptable Medium-Term Outcomes

Introduction/Research Question: Allosensitization, the presence of circulating anti-HLA antibodies, is a barrier in heart transplantation (HT), restricting the donor pool size, and leading to increased waitlist mortality and rejection risk post-HT. Desensitization therapies can be used to broaden the donor pool in highly sensitized patients, defined as pre-HT calculated panel reactive antibodies (cPRA)≥50%, for antibodies with mean fluorescence intensity (MFI)>10,000. There is paucity of data on longer-term outcomes in such high-immunological risk patients. Methods: Sensitized patients with pre-HT cPRA>50%, who were treated with desensitization and then received HT between 2011-2022 at Cedars-Sinai Medical Center were included. Desensitization therapies included bortezomib, rituximab, tocilizumab, obinutuzumab, intravenous immunoglobulin (IVIG), and plasmapheresis. cPRA, donor-specific antibody (DSA) levels, and post-HT clinical outcomes were assessed up to 5-year follow-up, loss to follow-up, or death. Results: 40 patients were analyzed. 77.5% of patients were female, and all had at least 1 risk factor for sensitization. cPRA decreased from 84.5±13.5% at baseline to 74.1±22.4% after completion of desensitization therapy, prior to transplant (p=0.005). Mean follow-up time post-HT was 4.3±2.9 years. 45.0% of patients had antibody-mediated rejection (AMR), 12.5% had CAV. Overall survival was 94.9%, 92.1%, and 87.5% at 1, 3, and 5 years respectively. All patients except 1 had normal left ventricular function at last follow-up. 72.5% of patients were transplanted in the presence of DSA, and 60.0% underwent post-HT induction with eculizumab in addition to antithymocyte globulin (ATG)/IVIG, while the remaining received ATG/IVIG alone. Among HT recipients with pre-formed DSA, 41.4% had high-level DSA (MFI > 10,000) at time of HT. At 6-12 months post-HT, only 17.2% had high-level DSA, and 41.4% had resolution of DSA. Conclusion: Highly sensitized HT candidates who underwent pre-HT desensitization had comparable survival and CAV rates as compared to the general HT population reported in the literature. However, sensitized patients experienced higher rates of AMR which were not associated with graft dysfunction or mortality.

Abstract 4140138: Coronary Artery Vasculopathy in a Cohort of 321 Heart Transplant Recipients: A Single Center Experience

Introduction: Despite advances in surgical techniques, organ preservation methods and immunosuppressant medications, the ten-year survival for orthotropic heart transplantation (OHT) remains around 50%. Coronary artery vasculopathy (CAV), among other factors, seems to have an important role in accelerated organ injury and failure. Aim: To determine the rate of survival and CAV development along with associated factors in a cohort of OHT recipients. Methods: Patients who underwent OHT at Virginia Commonwealth University (VCU) between October 2008 and September 2021 were retrospectively reviewed until June 2024. According to the VCU protocol, right heart biopsies were done weekly for the first month, every other week for the second month and at the first year mark post transplant. Left heart catheterizations were done one year after OHT and then at 2 year intervals. Survival, CAV development and need for percutaneous coronary interventions (PCI) as well as organ rejection rates in CAV patients were surveyed. Results: A total of 321 patients received OHT during that period with a median follow up time of 8.15 years from the date of transplant. Of these, 122 patients had 10-year follow up or more post OHT (53.27% survived) and 240 patients had 5-year follow up or more (66.25% survived). All patients had greater than 2.75 years of follow up. The overall mortality was 29.5%. CAV occurred in 55 patients out of 321 (17%) with median time of 2.82 years for CAV development. Mortality in the CAV group was 40% compared to 27% in the non-CAV group. Out of 55 patients with CAV, 19 required at least 1 PCI with 3 requiring interventions on chronic total occlusions. Evidence of rejection on right ventricle biopsy was observed in 51% of patients with CAV Conclusion: Our cohort had above average 10-year survival rate compared to the national data. Results revealed CAV is common post OHT and has implications on long term survival. Given CAV may develop in the absence of organ rejection, further studies are needed to identify factors associated with CAV and explore optimal treatment options that would potentially improve long-term survival post OHT.

Abstract 4144521: Racial disparities in heart transplantation: long term graft survival and non-mortality outcomes

Background: There is conflicting evidence on whether racial disparities still exist in heart transplant (HT) outcomes, with prior studies focusing primarily on differences in short-term mortality. We examined disparities in HT survival over a longer follow-up duration alongside a broader range of post-HT outcomes. Methods: Using the United Network for Organ Sharing (UNOS) database, we evaluated adult HT recipients between 2017 and 2022 and classified each according to race as either Black, non-Hispanic White and Other. The primary outcome was graft survival and secondary outcomes included rejection, renal dysfunction, and post-transplant diabetes. Chi-squared tests were used to compare baseline clinical factors and selected outcomes by racial group. Kaplan-Meier and Cox proportional hazards analyses were performed to compare risks of the primary outcome by race. Results: Among 15,873 recipients (63% non-Hispanic White, 23% Black, 14% Other), Black recipients were more often female, less often college educated, and more often had public (vs. private) insurance. Blacks had higher use of durable ventricular assist devices (VAD) and intra-aortic balloon pump (IABP) at the time of HT. Graft survival at one year did not differ by race (91.8% for Blacks vs. 91.1% for non-Blacks), but at three years was significantly lower for Blacks (83.4%) than non-Blacks (85.7%). Blacks had higher risk of graft failure after adjustment for baseline socioeconomic status (SES) and clinical variables (HR 1.28, CI 1.17 - 1.41). Blacks also had significantly higher prevalences of acute rejection (12.4% vs. 10.2%), diabetes (10.8% vs. 7.1%), and progression of renal dysfunction at 3-years post HT (40.9% vs. 37.1%; p < 0.05 for all). Conclusions: Racial disparities in graft survival after HT remain in the contemporary era but are only evident after longer-term follow-up. These survival disparities could be mediated by concurrent disparities in shorter term outcomes such as development of acute rejection, chronic kidney disease, and new onset diabetes.

Heart Transplantation Outcomes in Patients With Hypertrophic Cardiomyopathy in the Era of Mechanical Circulatory Support.

Mechanical circulatory support has emerged as a vital therapeutic modality for patients awaiting heart transplantation (HT). However, it is unknown how it affected the characteristics and post-HT outcomes of patients with hypertrophic cardiomyopathy (HCM). This retrospective cohort study analyzed adult HT recipients from the International Society for Heart and Lung Transplantation registry (1998-2017). Two equal-duration eras were defined: era 1 1998-2007 and era 2 2008-2017. Patients with HCM were compared across the two eras (n1 = 742 and n2 = 1,211) and within each era, they were contrasted with individuals with nonischemic (NICM) (n1 = 15,964 and n2 = 20,394) and ischemic cardiomyopathy (ICM) (n1 = 14,140 and n2 = 12,986). Across eras, the number of HTs among patients with HCM increased by 63%. The rate of recipients with HCM in the intensive care unit (ICU) supported with intra-aortic balloon pump (IABP) increased, yet their pre-HT functional status improved, and 5 year post-HT survival remained unchanged and favorable. In era 2, at the time of HT, patients with HCM were more frequently than their NICM and ICM counterparts in the ICU and supported with inotropes. In the same era, 1 and 5 year survival were more favorable in HCM compared to ICM and comparable to NICM.

Sodium-glucose co-transporter 2 inhibitors in left ventricular assist device and heart transplant recipients: a mini-review.

In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2i) emerged as promising therapeutic agents in managing heart failure (HF). They demonstrated a significant impact on reducing HF hospitalizations and related mortality in patients with reduced and preserved ejection fraction. However, evidence supporting their use in patients with left ventricular assist device (LVAD) and heart transplant (HT) recipients is still limited. We identified six key studies investigating the safety and efficacy of SGLT2i in LVAD and HT recipients. In patients with LVAD, prescription of SGLT2i was predominantly associated with improved fluid management and reduced pulmonary artery pressures. However, the results regarding their effects on body weight, hemoglobin A1c, diuretic use, and right ventricular function were contradictory. In terms of safety, SGLT2i were generally well-tolerated in the LVAD population, and the reported incidence of adverse events was low. In HT recipients, SGLT2i were associated with better glycemic control and weight reduction. No relevant adverse events were reported. Despite these encouraging results, the long-term safety and efficacy of SGLT2i in these vulnerable patient populations are yet to be investigated. Future randomized controlled trials are needed to address existing gaps in evidence and help integrate SGLT2i into clinical practice for LVAD and HT recipients.

Prevalence of Trypanosoma cruzi infection in Solid Organ Transplant recipients: a neglected disease in America

Abstract This study investigates the prevalence of Trypanosoma cruzi infection among solid organ transplant recipients in the United States from 2019 to 2023 before transplantation. Utilizing data from a large multicenter network, we identified a rising seroprevalence of 4.8% from 1523 Solid Organ Transplant Recipients at the time of the evaluation for transplantation, particularly among lung and heart transplant recipients. The findings highlight the need for improved screening protocols to address this neglected tropical disease in transplant populations.

Burden of atherogenic lipids and association with cardiac allograft vasculopathy in heart transplant recipients.

Cardiac Allograft Vasculopathy (CAV) is a leading cause of morbidity and mortality after heart transplantation. There are limited contemporary studies examining post-transplant lipid management and cardiometabolic health. We study the burden of cardiometabolic derangements post transplantation and its impact on CAV in a modern cohort of heart transplant recipients. All heart transplant (HTx) recipients between January 2019 and December 2020, with two lipid assessments and angiographic surveillance were included. Logistic regression was used to assess association of lipid levels with cardiovascular outcomes and CAV. Among 87 HTx recipients, atherogenic lipids were significantly elevated after Htx. Median LDL-C increased from a baseline level of 69.5 mg/dL to 86.5 mg/dL, p = 0.002, non-HDL-C 91.5 mg/dL to 118 mg/dL, p < 0.001, triglycerides 94.5 mg/dL to 133 mg/dL, p < 0.001, and remnant cholesterol 19 mg/dL to 27 mg/dL, p < 0.001. Increases in non-HDL-C, triglycerides, and remnant cholesterol were significantly associated with increased risk of CAV (Stanford Grade 4 and intimal thickness). Increases in triglycerides and remnant-C were associated with increased risk of composite major adverse cardiovascular events. We demonstrate a significant increase in atherogenic lipids two years following transplantation with low use (20 %) of high-intensity statin. Increase in atherogenic lipids was associated with increased risk of CAV and increase in triglycerides and remnant cholesterol with increased MACE. Future studies examining cardiometabolic consequences of heart transplantation and optimal treatment strategies to reduce risk of CAV and MACE are needed.

A qualitative account of mothers of pediatric heart transplant recipients' experience at a pilot mindfulness-based retreat: insights for implementation.

To explore participants' shared experience attending a pilot mindfulness-based retreat (MBR) intervention supporting the psychological well-being of mothers of pediatric heart transplant (HTx) recipients. A qualitative description approach was used within a larger hybrid mixed-methods pilot study evaluating the implementation-effectiveness of a 2-day MBR tailored specifically for a pediatric HTx population. A purposive sample of mothers was recruited from a leading Canadian pediatric HTx center, and each represented a primary, female-identifying caregiver, sharing residence with a pediatric HTx recipient of at least 4 months post-transplant. Two focus groups were conducted after and 16 individual interviews 3 months after the MBR to elicit participants' in-depth experience attending the MBR. Reflexive thematic data analysis led to theme development through an iterative process with consensus among team members. Sixteen mothers of pediatric HTx recipients (mean patient age 9.8 years; mean time post-transplant 8.2 years) participated in the MBR held in Ontario, Canada. Qualitative findings illuminated mothers' shared experience attending the MBR, reflecting three themes that describe key intervention elements beyond those affiliated with mindfulness practice alone: "respite," "readiness," and "relationships." Findings highlight acceptability and appropriateness as distinct yet interrelated implementation outcomes. Elements of "respite," "readiness," and "relationships" are key components of the MBR experience that offer valuable intervention and clinical considerations related to mothers' psychological well-being. Aligning intervention acceptability and appropriateness through tailored strategies may aid implementation. Future research considering maternal readiness relative to support intervention participation is warranted.

Early acute kidney injury after tacrolimus administration in heart transplant recipients receiving basiliximab induction therapy.

In this study, we aimed to analyze the association among the timing of tacrolimus initiation, time required to reach the target blood concentration, and early acute kidney injury (AKI) after tacrolimus administration in heart transplant recipients who received basiliximab induction therapy. 88 patients treated with tacrolimus-based immunosuppressive therapy were retrospectively reviewed. Induction therapy was administered to 52 patients. AKI was evaluated within 7 days of tacrolimus administration. The rate of increase in tacrolimus trough concentration to the target trough concentration of 10 µg/mL early after its administration was set to be similar in the basiliximab induction and non-induction group; 8 and 2 patients developed AKI in the induction and non-induction group, respectively. In the induction group, there was no significant difference in the timing of tacrolimus initiation and the time required to reach the target concentration between patients who developed and did not develop AKI. In contrast, the cumulative incidence of AKI was significantly different between patients with an estimated glomerular filtration rate below and those with an estimated glomerular filtration rate above 43 mL/min/1.73m2 at the start of tacrolimus administration (37.5% and 11.4%, respectively; p=0.045). In patients receiving basiliximab induction therapy, the timing of tacrolimus initiation and the time to reach the target concentration are unlikely to be associated with early AKI after tacrolimus administration. However, the recovery of sufficient renal function after heart transplantation is important for determining the start time of tacrolimus.

A Systematic Review of Reporting and Handling of Missing Data in Observational Studies Using the UNOS Database

BackgroundMissing data can undermine a registry’s ability to draw valid inferences by decreasing study power and introducing bias. We evaluated how missing data are reported and addressed in observational studies of adult heart transplantation (HT) recipients using the United Network for Organ Sharing (UNOS) database. MethodsWe conducted a systematic literature search of Medline from January 1st, 2018 through August 22nd, 2023 and included studies that used the UNOS database to evaluate adult (≥18 years) de novo HT recipients. We collected details on the study population, timeframe, primary endpoint, use of missing data, and whether and what methods were used to handle missing data. Approaches were classified as variable selection, complete case analysis (CCA), missing indicator method, single imputation, or multiple imputation. Results229 studies were included from 2018-2023. 67 (29.3%) studies limited their cohorts to those without missing data for the outcome or key variables and 93 (40.6%) reported missing data in their final cohort. 78 (34.1%) studies reported how they handled missing data in their statistical modeling. Of these, CCA was most used (n=41, 52.6%) followed by multiple imputation (n=22, 28.2%), and other methods (n=15, 19.2%) including a combination of missing indicator method (for binary variables) and single imputation. Thirty-one (13.5%) studies reported removing covariates from their analysis because of missing data. Only four (5.1%) studies reported sensitivity analysis to evaluate different missing data approaches. ConclusionsMerely a third of the identified UNOS database studies reported how they handled missing data in their analysis, with strategies varying. Although no singular approach to handling missing data exists, methods are available that can improve upon the most used approaches by, for example, reducing bias and increasing statistical power. Though these improvements are contingent on the missing data mechanism and the goals of the analysis. Future best practices should include explicit reporting of missingness, detailed methods, and sensitivity checks to maximize the credibility of UNOS database analyses.

The State of Combined Thoracoabdominal Triple Organ Transplantation in the United States

BackgroundAs triple organ transplants (TOT) have become more common, we evaluate patient characteristics, risk factors, and clinical outcomes of patients undergoing thoracoabdominal TOT. MethodsThis retrospective study utilized data from heart-lung-liver (HLL), heart-lung-kidney (HLK), heart-kidney-liver (HKL), and heart-kidney-pancreas (HKP) recipients from the UNOS registry between 1989 and 2023. Recipient and donor characteristics and risk factors for mortality were analyzed using Cox regression hazard models. Recipient survival up to 10-years were analyzed using the Kaplan-Meier method. ResultsDuring the study period, 81 TOTs were performed (13 HLLs, 13 HLKs, 46 HKLs, 9 HKPs). There were no statistically significant differences in long-term survival between TOTs (p=0.13). However, HLL and HLK recipients had significantly worse (p<0.0001) and improved (p<0.0001) survival, respectively, when compared to heart-lung, isolated heart, and lung transplant recipients. HLK was associated with improved survival (HR:0.22, p=0.033). We found no differences in survival among HKL (p=0.24) and HKP (p=0.19) recipients compared to their dual- and single-organ counterparts. TOTs after 2007 (HR: 0.29, p=0.003) were associated with improved survival, whereas increased recipient age (HR:1.06, p=0.037), eGFR (HR:1.02, p=0.005), and donor age (HR:1.05, p=0.031) were associated with higher mortality. ConclusionsThe prevalence of TOTs has dramatically increased over the past decade. While overall survival between TOTs appears similar, adding a liver to a heart-lung transplant may be associated with a poorer prognosis compared to adding a kidney. A careful, multidisciplinary approach to patient selection and management remains paramount in optimizing outcomes for high-risk patients undergoing TOTs.

Therapeutic Plasma Exchange is Associated with Increased Survival in Heart Transplant Recipients Experiencing Severe Primary Graft Dysfunction

Therapeutic Plasma Exchange is Associated with Increased Survival in Heart Transplant Recipients Experiencing Severe Primary Graft Dysfunction

Peripheral versus central cannulation of VA-ECMO for primary graft dysfunction after heart transplantation: a systematic review and meta-analysis

Severe primary graft dysfunction (PGD) after heart transplantation (HT) is a major cause of death and requires veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Given the wide between-center variability in cannula configuration, we conducted a systematic review and metanalysis including studies of adult HT recipients who required VA-ECMO for PGD to determine whether a peripheral or central configuration was associated with higher mortality. The primary endpoints were short-term and one-year mortality. Secondary endpoints were VA-ECMO-related complications. Overall, we included 16 studies comprising 874 patients from 33 centers. Using a random effects model, peripheral cannulation was associated with a non-significant reduction in short-term mortality (OR=0.73, 95%CI=0.41–1.28, I2=55.8%) and a significant reduction in one-year mortality (OR=0.60, 95%CI=0.37–0.97, I2=35.9%). Peripheral cannulation decreased risk of bleeding but increased risk of limb ischemia and infection, with similar rates of stroke and need for renal replacement therapy. Overall, certainty of evidence was low.

Examining Risk Factors Related to Cardiac Rehabilitation Cessation Among Patients With Advanced Heart Failure.

Cardiac rehabilitation (CR) is beneficial in heart transplant and left ventricular assist device (LVAD) recipients, but patterns of attendance remain poorly understood. We describe CR adherence and cessation in this population. We performed a retrospective review of heart transplant and LVAD recipients who attended ≥1 CR session at a tertiary medical center (2013-2022). Complete adherence was defined as attending 36 sessions. Primary reasons for cessation before 36 sessions were recorded. We compared post-operative complications, duration of hospitalization, and readmissions between participants with and without complete adherence using logistic and linear regressions. Among participants with complete adherence, we compared changes in metabolic equivalent of task (MET), exercise time, and peak oxygen uptake using paired sample t tests. There were 137 heart transplant and LVAD recipients (median age 56.9years, 74% male) who attended CR. Among them, 91% either completed 36 CR sessions or <24 sessions. Among those without complete adherence (n=74), 72% reported medical reasons, and 15% reported personal reasons for cessation. Compared to those who completed CR, those without complete adherence experienced more post-operative complications (44% vs 24%, P =.02) and major bleeding (23% vs 7%, P =.02) prior to CR. Participants with complete adherence experienced significant improvements in exercise time (142.5seconds), MET (0.4), and peak oxygen uptake (1.4 mL/kg/min). Nearly half of heart transplant and LVAD recipients in CR completed all 36 sessions. Those with complete adherence experienced significant improvements in exercise measures, underscoring the important benefits of CR in this population.

OSTEO18, a novel urinary proteomic signature, associated with osteoporosis in heart transplant recipients

Abstract Background Immunosuppressive treatment in heart transplant (HTx) recipient causes osteoporosis. The urinary proteomic profile (UPP) includes peptide fragments derived from the bone extracellular matrix. Purpose Study aims were to develop and validate a multidimensional UPP biomarker for osteoporosis in HTx patients from single sequenced urinary peptides identifying the parent proteins. Methods A single-center HTx cohort was analyzed. Urine samples were measured by capillary electrophoresis coupled with mass spectrometry. Cases with osteoporosis and matching controls were randomly selected from all available 389 patients. In derivation case-control dataset, 1576 sequenced peptides detectable in ≥30% of patients. Applying statistical analysis on these, an 18-peptide multidimensional osteoporosis UPP biomarker (OSTEO18) was generated by support vector modeling. The 2 replication datasets included 118 and 94 patients. For further validation, the whole cohort was analyzed. Statistical methods included logistic regression and receiver operating characteristic curve (ROC) analysis. Results In derivation dataset, the AUC, sensitivity and specificity of OSTEO18 were 0.83 (95% CI: 0.76-0.90), 74.3% and 87.1%, respectively. In replication datasets, results were confirmatory. In the whole cohort (154 osteoporotic patients [39.6%]), the ORs for osteoporosis increased (p &amp;lt; 0.0001) across OSTEO18 quartiles from 0.39 (95% CI: 0.25-0.61) to 3.14 (2.08-4.75). With full adjustment for known osteoporosis risk factors, OSTEO18 improved AUC from 0.708 to 0.786 (p = 0.0003) for OSTEO18 categorized (optimized threshold: 0.095) and to 0.784 (p = 0.0004) for OSTEO18 as continuously distributed classifier. Conclusion OSTEO18 is a clinically meaningful novel biomarker indicative of osteoporosis in HTx recipients and is being certified as in-vitro diagnostic.

Treatment with mTOR Inhibitors as primary immunosuppression after combined heart and kidney transplantation

Abstract Background It has been hypothesized that combined heart and kidney transplantation (HKT) may lead to immune modulation and attenuation of cardiac allograft vasculopathy (CAV) progression. Sirolimus (SRL) has been shown to mitigate the progression of CAV and confer renal protection. With the increasing use of SRL as primary immunosuppression in heart transplant (HT) recipients, the effect of HKT on CAV progression compared to HT-only remains undetermined. Purpose We sought to investigate the patterns of conversion from calcineurin inhibitors (CNI) to SRL, and its impact on CAV progression and outcomes in HKT compared to HT-only in a cohort with frequent use of SRL as primary immunosuppression. Methods A cohort of 302 patients who underwent either HT only (n=262) or combined HKT (n=40) was analyzed. CAV progression was assessed by measuring the delta (Δ) annual change in plaque volume (PV) normalized to vessel length (PV/VL in mm3/mm) and plaque index (PI) (%) (calculated as the PV to VV ratio) between baseline and last follow-up coronary intravenous ultrasound (IVUS). Clinical adverse outcomes included all-cause death and CAV-associated events. Secondary outcomes included differences in renal function and incidence of SRL-associated proteinuria (defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL) between HT-only and HKT recipients. Results Overall, 217 (72%) patients were converted from CNI to SRL as primary immunosuppression. HT recipients were more likely to be converted to SRL than combined HKT recipients (74% vs. 55%, P=0.01). HKT was associated with significantly higher ΔPV/VL (P=0.01) and a trend toward a higher ΔPI (P=0.06) than HT-only, but this association was markedly attenuated after adjustment to SRL conversion. HKT was associated with similar risk of death (adjusted hazard ratio [HR] 0.69, 95%CI: 0.28-1.71, P=0.43) and CAV-related events (adjusted HR 0.83, 95% CI: 0.30-2.31, P=0.72). Conversion to SRL was significantly associated with decreased risk of death and CAV-related events in the overall cohort. This association was not modified by the type of organ transplantation (Pinteraction=NS), and without a significant effect on estimated glomerular filtration rate (eGFR) or proteinuria. Conclusions HKT recipients compared to HT-only were less likely to be converted from CNI to SRL-based immunosuppression and had a greater CAV progression but without significant differences in all-cause mortality or CAV-related events. The clinical benefit and safety of conversion to SRL appeared similar in the HKT and isolated HT cohorts.

Altered clot formation and fibrinolysis in heart transplant recipients

Abstract Background Long-term survival after heart transplantation (HTx) is limited by cardiac allograft vasculopathy (CAV), a frequent accelerated form of coronary artery disease. The pathogenesis remains incompletely understood, but thrombosis may be involved. We aimed to investigate clot formation and fibrinolysis in HTx patients and relate the findings to prognosis. Methods This prospective cohort study included 69 patients (median 8.4 years after HTx) with angiographically documented CAV 0 (not significant, n=36), CAV 1 (mild, n=19), and CAV 2-3 (moderate to severe, n=14). Healthy individuals (n=69) served as age- and gender-matched controls. Using a plasma-based fibrin clot formation and lysis assay, we assessed the following clot properties off-aspirin: 1) clot formation reflected by peak absorbance, 2) fibrinolysis measured by clot lysis time, and 3) a combined measure of clot formation and lysis reflected by area under the curve (AUC). Major adverse cardiac events (MACE) included heart failure hospitalization, cardiovascular death, and significant CAV progression. Results Median follow-up time was 5.1 (2.1-5.9) years. Five CAV 2-3 patients were excluded as it was not considered safe to interrupt aspirin therapy. Five patients had missing values due to either lysis resistance or severely decreased fibrin formation, and four of these underwent MACE with CAV progression and/or heart failure during follow up. Peak absorbance was significantly higher in HTx patients compared with healthy controls (0.72 vs. 0.50 aggregation units (AU), p&amp;lt;0.0001). Further, a stepwise increment above reference range through CAV groups was seen; CAV 2-3 patients (0.85 ± 0.12 AU) versus CAV 1 patients (0.72 ± 0.17 AU, p&amp;lt;0.05) and CAV 0 patients (0.68 ± 0.27 AU, p=0.06). Clot lysis time was significantly longer in HTx patients compared with healthy controls (1275 vs. 733 seconds, p&amp;lt;0.0001). AUC was significantly increased compared with healthy controls (1399 vs. 547 AU x seconds, p&amp;lt;0.0001). Overall, clot formation and fibrinolysis was not related to MACE. Conclusion HTx-patients have increased clot formation and prolonged fibrinolysis compared with healthy controls. Further, HTx-patients have an increased combined measure of these parameters compared with healthy controls, suggesting imbalance between fibrin clot formation and fibrinolysis. None of the measured parameters were related to prognosis.Clot formation and fibrinolysis