Clinical Utility of Donor-Derived Cell-Free DNA in Heart Transplant Recipients With Multi-Organ Transplants.

BACKGROUND: Donor-derived cell-free DNA (dd-cfDNA) has emerged as a reliable, noninvasive method for the surveillance of allograft rejection in heart transplantation (HT) patients, but its utility in multi-organ transplants (MOT) is unknown. We describe our experience using dd-cfDNA in simultaneous MOT recipients. METHODS: A single-center retrospective review of all HT recipients between 2018 and 2022 that had at least one measurement of dd-cfDNA collected. Patients who had simultaneous MOT were identified and included in this study. Levels of dd-cfDNA were paired with endomyocardial biopsies (EMB) performed within 1 month of blood testing if available. Acute cellular rejection (ACR) was defined as ISHLT (International Society for Heart and Lung Transplantation) grade ≥ 2R. and antibody-mediated rejection (AMR) was defined as pAMR grade > 0. The within-patient variability score of the dd-cfDNA was calculated by the variance/average. RESULTS: The study included 25 multiorgan transplant recipients: 13 heart-kidney (H-K), 8 heart-liver (H-Li), and 4 heart-lung (H-Lu). The median age was 55 years, 44% were female; the median time from HT until the first dd-cfDNA measurement was 4.5 months (IQR 2, 10.5). The median dd-cfDNA level was 0.18% (IQR 0.15%, 0.27%) for H-K, 1.15% (IQR 0.77%, 2.33%) for H-Li, and 0.69% (IQR 0.62%, 1.07%) for H-Lu patients (p < 0.001). Prevalence of positive dd-cfDNA tests (threshold of 0.20%) were 42.2%, 97.3%, and 92.3% in the H-K, H-Li, and H-Lu groups, respectively. The within-patient variability score was highest in the H-Li group (median of 0.45 [IQR 0.29, 0.94]) and lowest in the H-K group (median of 0.09 [IQR 0.06, 0.12]); p = 0.002. No evidence of cardiac ACR or AMR was found. Three patients experienced renal allograft ACR and/or AMR, two patients experienced rejection of the liver allograft, and one patient experienced an episode of AMR-mediated lung rejection. One person in the H-K group experienced an episode of cardiac allograft dysfunction that was not associated with biopsy-confirmed rejection. CONCLUSION: Dd-cfDNA is chronically elevated in most MOT recipients. There is a high degree of within-patient variability in levels (particularly for H-Li and H-Lu recipients), which may limit the utility of this assay in monitoring MOT recipients.

CAV Trajectories Among Patients With No or Mild CAV at 10 Years Posttransplant.

Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (HT). Prior studies identified distinct CAV trajectories in the early post-HT period with unique predictors, but the evolution of CAV in later periods is not well-described. This study assessed the prevalence of late CAV progression and associated risk factors in HT recipients with ISHLT CAV 0/1 at 10 years post-HT. Consecutive adult patients who underwent HT from January 2000 to December 2008 were evaluated and grouped by CAV trajectories into progressors (developed ISHLT CAV 2/3) or nonprogressors (remained ISHLT CAV 0/1). A total of 130 patients were included with a median age at angiography of 61.7 years and a median follow-up time of 4.8 years. 8.5% progressed to CAV 2/3, while the remaining 91.5% were nonprogressors. Progression was not associated with death or retransplantation (27.3% [progressor] vs. 21.0% [nonprogressor], p = 0.70). These data may inform shared decision-making about late CAV screening.

Association of Hemometabolic Trajectory and Mortality: Insights From the Cardiogenic Shock Working Group Registry.

Cardiogenic shock (CS) is a hemodynamic syndrome that can progress to systemic metabolic derangements and end-organ dysfunction. Prior studies have reported hemodynamic parameters at the time of admission to be associated with mortality but hemodynamic trajectories in CS have not been well described. We studied the association between hemodynamic profiles and their trajectories and in-hospital mortality in patients with CS due to heart failure (HF-CS) and acute myocardial infarction (MI-CS). Using data from the large multicenter Cardiogenic Shock Working Group (CSWG) registry, we analyzed hemodynamic data obtained at the time of pulmonary artery catheter (PAC) insertion (dataset at baseline) and at PAC removal or death (dataset at final time point). Univariable regression analyses for prediction of in-hospital mortality were conducted for baseline and final hemodynamic values, as well as the interval change (delta-P). Data was further analyzed based on CS etiology and survival status. A total of 2260 patients with PAC data were included (70% male, age 61 ± 14 years, 61% HF-CS, 27% MI-CS). In-hospital mortality was higher in the MI-CS group (40.1%) compared with HF-CS (22.4%, P < .01). In the HF-CS cohort, survivors exhibited lower right atrial pressure (RAP), pulmonary artery pressure (PAP), cardiac output/index (CO/CI), lactate, and higher blood pressure (BP) than nonsurvivors at baseline. In this cohort, during hospitalization, improvement in metabolic (aspartate transaminase, lactate), BP, hemodynamic (RAP, pulmonary artery pulsatility index [PAPi], pulmonary artery compliance for right-sided profile and CO/CI for left-sided profile), had association with survival. In the MI-CS cohort, a lower systolic BP and higher PAP at baseline were associated with odds of death. Improvement in metabolic (lactate), BP, hemodynamic (RAP, PAPi for right-sided profile and CO/CI for left-sided profile) were associated with survival. In a large contemporary CS registry, hemodynamic trajectories had a strong association with short-term outcomes in both cohorts. These findings suggest the clinical importance of timing and monitoring hemodynamic trajectories to tailor management in patients with CS.

Recurrent melanoma 25 years after initial diagnosis, presenting as metastatic disease early after heart transplantation.

BACKGROUND: Cancer survivors (CS) comprise a particularly high-risk group for both de-novo and recurrent malignancies after solid organ transplantation. CASE PRESENTATION: We report a case of relapsed melanoma, presented as metastatic disease seven months after heart transplantation in a patient who had an early-stage melanoma resected 25 years prior. Treatment with a combination of dabrafenib, a BRAF inhibitor, and trametinib, a mitogen-activated protein kinase (MEK) inhibitor resulted in a near-complete metabolic response, without major adverse effects. CONCLUSION: This case demonstrates the increased risk of recurrence in CS with melanoma, which can persist decades after cancer diagnosis. These patients may be amenable to treatment using modern treatment modalities in oncology.

Mechanical circulatory support for cardiogenic shock during the peripartum period.

BACKGROUND: Cardiomyopathies account for more than half of the cardiovascular disease during the peripartum period. In the extreme, patients may present with cardiogenic shock (CS) requiring mechanical circulatory support (MCS). The aim of this study was to report our experience with CS requiring MCS in the peripartum period. METHODS: We present a single-center retrospective analysis of all CS cases involving MCS during the peripartum period that occurred between 2012 and 2023. RESULTS: Eleven cases were included. Median age was 33, median BMI was 30.4, and 73% underwent a caesarian-section for delivery. CS presentation occurred in 36.4% during pregnancy and in 63.6% after delivery. Most patients were in Society for Cardiovascular Angiography & Interventions (SCAI) Stage C shock and in 37% the suspected etiology was peripartum cardiomyopathy. MCS usage included intra-aortic balloon pump (4), Impella microaxial blood pump (2), veno-arterial extracorporeal membrane oxygenation (6), and temporary right ventricle assist devices (2), with some patients having multiple MCS devices. The rate of major complications was 36.4%. During a median follow-up of 4.5 years, 7 patients had sustained cardiac recovery (63.6%), 1 patient (9.1%) underwent cardiac transplantation, 2 patients (18.2%) received a durable LVAD, and 2 (18.2%) have died. CONCLUSION: MCS in severe CS cases during the peripartum period is rare and associated with favorable outcomes. High recovery rates suggest favoring first MCS/LVAD over transplant.

Serial Shock Severity Assessment Within 72 Hours After Diagnosis: A Cardiogenic Shock Working Group Report.

BACKGROUND: The Cardiogenic Shock Working Group-modified Society for Cardiovascular Angiography and Interventions (CSWG-SCAI) staging was developed to risk stratify cardiogenic shock (CS) severity. Data showing progressive changes in SCAI stages and outcomes are limited. OBJECTIVES: We investigated serial changes in CSWG-SCAI stages and outcomes of patients presenting with cardiogenic shock complicating acute myocardial infarction (MI-CS) and heart failure-related CS (HF-CS). METHODS: The multicenter CSWG registry was queried. CSWG-SCAI stages were computed at CS diagnosis and 24, 48, and 72 hours. RESULTS: A total of 3,268 patients (57% HF-CS; 27% MI-CS) were included. At CS diagnosis, CSWG-SCAI stage breakdown was 593 (18.1%) stage B, 528 (16.2%) stage C, 1,659 (50.8%) stage D, and 488 (14.9%) noncardiac arrest stage E. At 24 hours, >50% of stages B and C patients worsened, but 86% of stage D patients stayed at stage D. Among stage E patients, 54% improved to stage D and 36% stayed at stage E by 24 hours. Minimal SCAI stage changes occurred beyond 24 hours. SCAI stage trajectories were similar between MI-CS and HF-CS groups. Within 24 hours, unadjusted mortality rates of patients with any SCAI stage worsening or improving were 44.6% and 34.2%, respectively. Patients who presented in or progressed to stage E by 24 hours had the worst prognosis. Survivors had lower lactate than nonsurvivors. CONCLUSIONS: Most patients with CS changed SCAI stages within 24 hours from CS diagnosis. Stage B patients were at high risk of worsening shock severity by 24 hours, associated with excess mortality. Early CS recognition and serial assessment may improve risk stratification.

Added prognostic value of visually estimated coronary artery calcium among heart transplant recipients.

BACKGROUND: Cardiac hybrid positron emission tomography/computed tomography (PET/CT) has become a valid screening modality for cardiac allograft vasculopathy (CAV) following heart transplantation (HT). Visually estimated coronary artery calcium (VECAC) can be quantified from CT images obtained as part of PET/CT and has been shown to be associated with adverse cardiovascular outcomes in coronary artery disease. We investigated the prognostic value of VECAC following HT. METHODS: A retrospective analysis of 430 consecutive adult HT patients who underwent 13N-ammonia cardiac PET/CT from 2016 to 2019 with follow-up through October 15, 2022, was performed. VECAC categories included: VECAC 0, VECAC 1-9, VECAC 10-99, and VECAC 100+. The association between VECAC categories and outcomes was assessed using univariable and multivariable proportional hazards regression. The primary outcome was death/retransplantation. RESULTS: The cohort was 73% male, 33% had diabetes, 67% had estimated glomerular filtration rate <60 ml/min, median age was 61 years, and median time since HT was 7.5 years. VECAC alone was insufficiently sensitive to screen for CAV. During a median follow-up of 4.2 years ninety patients experienced death or retransplantation. Compared with those with VECAC 0, patients VECAC 10-99 (HR 2.25, 95% CI 1.23-4.14, p = 0.009) and VECAC 100+ (HR 3.42, 95% CI 1.96-5.99, p < 0.001) experienced an increased risk of death/retransplantation. The association was similar for cardiovascular death and cardiovascular hospitalization. After adjusting for other predictors of death/retransplantation, VECAC 10-99 (VECAC 10-99: aHR 1.95, 95% CI 1.03-3.71 p = 0.04) and VECAC 100+ (VECAC 100+: aHR 2.33, 95% CI 1.17-4.63, p = 0.02) remained independently associated with death/retransplantation. CONCLUSIONS: VECAC is an independent prognostic marker of death/retransplantation following HT and merits inclusion as a part of post-HT surveillance PET/CT.

Relationship between indexed surgery and postcardiotomy extracorporeal life support outcomes.

OBJECTIVES: Veno-arterial extracorporeal life support (V-A ECLS) is increasingly being utilized for postcardiotomy shock (PCS), though data describing the relationship between type of indexed operation and outcomes are limited. This study compared V-A ECLS outcomes across four major cardiovascular surgical procedures. METHODS: This was a single-center retrospective study of patients who required V-A ECLS for PCS between 2015 and 2022. Patients were stratified by the type of indexed operation, which included aortic surgery (AoS), coronary artery bypass grafting (CABG), valve surgery (Valve), and combined CABG and valve surgery (CABG + Valve). Factors associated with postoperative outcomes were assessed using logistic regression. RESULTS: Among 149 PCS patients who received V-A ECLS, there were 35 AoS patients (23.5%), 29 (19.5%) CABG patients, 59 (39.6%) Valve patients, and 26 (17.4%) CABG + Valve patients. Cardiopulmonary bypass times were longest in the AoS group (p < 0.01). Regarding causes of PCS, AoS patients had a greater incidence of ventricular failure, while the CABG group had a higher incidence of ventricular arrhythmia (p = 0.04). Left ventricular venting was most frequently utilized in the Valve group (p = 0.07). In-hospital mortality was worst among CABG + Valve patients (p < 0.01), and the incidence of acute kidney injury was highest in the AoS group (p = 0.03). In multivariable logistic regression, CABG + Valve surgery (odds ratio (OR) 4.20, 95% confidence interval 1.30-13.6, p = 0.02) and lactate level at ECLS initiation (OR, 1.17; 95% CI, 1.06-1.29; p < 0.01) were independently associated with mortality. CONCLUSIONS: We demonstrate that indications, management, and outcomes of V-A ECLS for PCS vary by type of indexed cardiovascular surgery.

Feasibility of veno-arterial extracorporeal life support in awake patients with cardiogenic shock.

OBJECTIVES: This study sought to demonstrate outcomes of veno-arterial extracorporeal life support (VA-ECLS) in non-intubated ('awake') patients with cardiogenic shock, as very few studies have investigated safety and feasibility in this population. METHODS: This was a retrospective review of 394 consecutive VA-ECLS patients at our institution from 2017 to 2021. We excluded patients cannulated for indications definitively associated with intubation. Patients were stratified by intubation status at time of cannulation and baseline differences were balanced by inverse probability of treatment weighting. The primary outcome was in-hospital mortality while secondary outcomes included adverse events during ECLS and destination at discharge. RESULTS: Out of 135 patients in the final cohort, 79 were intubated and 56 were awake at time of cannulation. All awake patients underwent percutaneous femoral cannulation with technical success of 100% without intubation. Indications for VA-ECLS in awake patients included acute decompensated heart failure (64.3%), pulmonary hypertension or massive pulmonary embolism (12.5%), myocarditis (8.9%) and acute myocardial infarction (5.4%). After adjustment, awake and intubated patients had similar ECLS duration (7 vs 6 days, P = 0.19), in-hospital mortality (39.6% vs 51.7%, P = 0.28), and rates of various adverse events. Intubation status was not a significant risk factor for 90-day mortality (hazard ratio [95% confidence interval]: 1.26 [0.64, 2.45], P = 0.51) in multivariable analysis. Heart transplantation (15.1% vs 4.9%) and ventricular assist device (17.4% vs 2.2%) were more common destinations at discharge in awake patients than intubated patients (P = 0.02). CONCLUSIONS: Awake VA-ECLS is safe and feasible with comparable outcomes as intubated counterparts in select cardiogenic shock patients.

Clinical Utility of the Molecular Microscope Diagnostic System in a Real-World Transplant Cohort: Moving Towards a New Paradigm.

Objectives: To evaluate the clinical implications of adjunctive molecular gene expression analysis (MMDx ) of biopsy specimens in heart transplant (HT ) recipients with suspected rejection. Introduction: Histopathological evaluation remains the standard method for rejection diagnosis in HT. However, the wide interobserver variability combined with a relatively common incidence of "biopsy-negative" rejection has raised concerns about the likelihood of false-negative results. MMDx, which uses gene expression to detect early signs of rejection, is a promising test to further refine the assessment of HT rejection. Methods: Single-center prospective study of 418 consecutive for-cause endomyocardial biopsies performed between November 2022 and May 2024. Each biopsy was graded based on histology and assessed for rejection patterns using MMDx. MMDx results were deemed positive if borderline or definitive rejection was present. The impact of MMDx results on clinical management was evaluated. Primary outcomes were 1-year survival and graft dysfunction following MMDx-guided clinical management. Secondary outcomes included changes in donor-specific antibodies, MMDx gene transcripts, and donor-derived cell-free DNA (dd-cfDNA) levels. Results: We analyzed 418 molecular samples from 237 unique patients. Histology identified rejection in 32 cases (7.7%), while MMDx identified rejection in 95 cases (22.7%). Notably, in 79 of the 95 cases where MMDx identified rejection, histology results were negative, with the majority of these cases being antibody-mediated rejection (62.1%). Samples with rejection on MMDx were more likely to show a combined elevation of dd-cfDNA and peripheral blood gene expression profiling than those with borderline or negative MMDx results (36.7% vs 28.0% vs 10.3%; p<0.001). MMDx results led to the implementation of specific antirejection protocols or changes in immunosuppression in 20.4% of cases, and in 73.4% of cases where histology was negative and MMDx showed rejection. 1-year survival was better in the positive MMDx group where clinical management was guided by MMDx results (87.0% vs 78.6%; log rank p=0.0017). Conclusions: In our cohort, MMDx results more frequently indicated rejection than histology, often leading to the initiation of antirejection treatment. Intervention guided by positive MMDx results was associated with improved outcomes.

Cardio-Renal-Metabolic Outcomes Associated With the Use of GLP-1 Receptor Agonists After Heart Transplantation.

BACKGROUND: The use of glucagon-like-peptide 1 receptor agonists (GLP1-RA) has dramatically increased over the past 5 years for diabetes mellitus type 2 (T2DM) and obesity. These comorbidities are prevalent in adult heart transplant (HT) recipients. However, there are limited data evaluating the efficacy of this drug class in this population. The aim of the current study was to describe cardiometabolic changes in HT recipients prescribed GLP1-RA at a large-volume transplant center. METHODS: We retrospectively reviewed all adult HT recipients who received GLP1-RA after HT for a minimum of 1-month. Cardiometabolic parameters including body mass index (BMI), lipid panel, hemoglobin A1C, estimated glomerular filtration rate (eGFR), and NT-proBNP were compared prior to initiation of the drug and at most recent follow-up. We also evaluated for significant dose adjustments to immunosuppression after drug initiation and adverse effects leading to drug discontinuation. RESULTS: Seventy-four patients were included (28% female, 53% White, 20% Hispanic) and followed for a median of 383 days [IQR 209, 613] on a GLP1-RA. The majority of patients (n = 56, 76%) were prescribed semaglutide. The most common indication for prescription was T2DM alone (n = 33, 45%), followed by combined T2DM and obesity (n = 26, 35%). At most recent follow-up, mean BMI decreased from 33.3 to 31.5 kg/m2 (p < 0.0001), HbA1C from 7.3% to 6.7% (p = 0.005), LDL from 78.6 to 70.3 mg/dL (p = 0.018) and basal insulin daily dose from 32.6 to 24.8 units (p = 0.0002). CONCLUSION: HT recipients prescribed GLP1-RA therapy showed improved glycemic control, weight loss, and cholesterol levels during the study follow-up period. GLP1-RA were well tolerated and were rarely associated with changes in immunosuppression dosing.

Validation of the HeartMate 3 survival risk score in a large left ventricular assist device center.

OBJECTIVE: The HeartMate 3 survival risk score was recently validated in the Multicenter study Of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 to predict patient-specific survival in HeartMate 3 left ventricular assist device candidates. The HeartMate 3 survival risk score stratifies individuals into tertiles according to survival probability. METHODS: We performed a single-center retrospective review of all HeartMate 3 left ventricular assist device recipients between September 2017 and August 2022. Baseline characteristics were collected from the electronic medical records. HeartMate 3 survival risk scores were calculated for all eligible patients. One- and 2-year Kaplan-Meier survival analyses were conducted. A univariate and multivariable Cox regression model was used to identify predictors. RESULTS: A total of 181 patients were included in this final analysis. The median age was 62 years, 83% were male, and 26% were Interagency Registry for Mechanically Assisted Circulatory Support Profile 1. The mean HeartMate 3 survival risk score for the entire cohort was 2.66 ± 0.66. Two-year survivals in the high, average, and low survival groups were 93.5% ± 3.2%, 81.6% ± 7.4%, and 82.0% ± 6.6%, respectively. As a continuous variable, the unadjusted HeartMate 3 survival risk score was a significant predictor of mortality (hazard ratio, 2.20; 95% CI, 1.08-4.45; P = .029). The areas under the curve were 0.70 and 0.66 at 1 and 2 years, respectively. We were unable to demonstrate the discriminatory ability of the HeartMate 3 survival risk score using the original stratification, but we found significantly increased survival in the high survival group using a binary cutoff (hazard ratio, 4.8; 95% CI, 1.01-20.9; P = .038). CONCLUSIONS: The unadjusted HeartMate 3 survival risk score was associated with postimplant survival in patients outside of the Multicenter study Of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 but did not remain an independent predictor after adjusting for ischemic etiology and severe diabetes. The HeartMate 3 survival risk score was able to identify patients at high survival using a binary cutoff, but we were unable to demonstrate its discriminatory ability among the previously published risk tertiles.

Comparative Analysis of Ischemia-Reperfusion Injury in Heart Transplantation: A Single-Center Study Evaluating Conventional Ice-Cold Storage versus the Paragonix SherpaPak Cardiac Transport System.

BACKGROUND: Since the 2018 allocation system change in heart transplantation (HT), ischemic times have increased, which may be associated with peri-operative and post-operative complications. This study aimed to compare ischemia reperfusion injury (IRI) in hearts preserved using ice-cold storage (ICS) and the Paragonix SherpaPak TM Cardiac Transport System (CTS). METHODS: From January 2021 to June 2022, consecutive endomyocardial biopsies from 90 HT recipients were analyzed by a cardiac pathologist in a single-blinded manner: 33 ICS and 57 CTS. Endomyocardial biopsies were performed at three-time intervals post-HT, and the severity of IRI manifesting histologically as coagulative myocyte necrosis (CMN) was evaluated, along with graft rejection and graft function. RESULTS: The incidence of IRI at weeks 1, 4, and 8 post-HT were similar between the ICS and CTS groups. There was a 59.3% statistically significant reduction in CMN from week 1 to 4 with CTS, but not with ICS. By week 8, there were significant reductions in CMN in both groups. Only 1 out of 33 (3%) patients in the ICS group had an ischemic time >240 mins, compared to 10 out of 52 (19%) patients in the CTS group. During the follow-up period of 8 weeks to 12 months, there were no significant differences in rejection rates, formation of de novo donor-specific antibodies and overall survival between the groups. CONCLUSION: The CTS preservation system had similar rates of IRI and clinical outcomes compared to ICS despite longer overall ischemic times. There is significantly more recovery of IRI in the early post operative period with CTS. This study supports CTS as a viable option for preservation from remote locations, expanding the donor pool.

Frequency of Comfort Care and Palliative Care Consultation after ST-Elevation Myocardial Infarction.

INTRODUCTION: ST-elevation myocardial infarction (STEMI) remains a leading cause of death despite advances in revascularization and post-STEMI care. Especially for patients with a poor prognosis, there is increasing emphasis on comfort-focused care. METHODS: We conducted a single-center retrospective cohort study of patients with STEMI at a large tertiary care academic medical center, abstracting patient-level data, causes of death, and use of palliative care consultation from the medical records. We sought to investigate the frequency of comfort-focused approaches and palliative care consultation after STEMI. RESULTS: A total of 536 patients presented with or were transferred with STEMI from January 2010 to July 2018, of whom 61/536 (11.4%) died during index hospitalization. Among those who underwent percutaneous intervention (PCI), the in-hospital mortality rate was 6.8%. Median (IQR) and time to death was two (0-6) days. Among those who died, 25/61 (41%) were treated with mechanical circulatory support (MCS). A total of 25/61 (41%) patients died following transition to a comfort-focused approach. Rate of MCS utilization during hospitalization was higher in the group that was ultimately transitioned to comfort-focused measures than the group who received full treatment measures. Palliative care was consulted in the case of 6/61 (9.8%) patients. Median time to consultation was 5 (1-7) days and time to death was 6.5 (2-28) days. DISCUSSION: Transition to comfort-focused care before death after STEMI is common, particularly in those with cardiogenic shock and/or treated with MCS, highlighting the critical status of such patients. Although increasingly employed in recent years, palliative care consults remain rare and are often employed late in the hospitalization.

Clinical outcomes among cardiogenic shock patients supported with high-capacity Impella axial flow pumps: A report from the Cardiogenic Shock Working Group.

BACKGROUND: The Impella 5.0 and 5.5 pumps (Abiomed, Danvers, MA) are large-bore transvalvular micro-axial assist devices used in cardiogenic shock (CS) for patients requiring high-capacity flow. Despite their increasing use, real-world data regarding indications, rates of utilization and clinical outcomes with this therapy are limited. The objective of our study was to examine clinical profiles and outcomes of patients in a contemporary, real-world CS registry of patients who received an Impella 5.0/5.5 alone or in combination with other temporary mechanical circulatory support (tMCS) devices. METHODS: The CS Working Group (CSWG) Registry includes patients from 34 US hospitals. For this analysis, data from patients who received an Impella 5.0/5.5 between 2020-2023 were analyzed. Use of Impella 5.0/5.5 with or without additional tMCS therapies, duration of support, adverse events and outcomes at hospital discharge were studied. Adverse events including stroke, limb ischemia, bleeding and hemolysis were not standardized by the registry but reported per individual CSWG Primary Investigator discretion. For those who survived, rates of native heart recovery (NHR) or heart replacement therapy (HRT) including heart transplant (HT), or durable ventricular assist device (VAD) were recorded. We also assessed outcomes based on shock etiology (acute myocardial infarction or MI-CS vs. heart failure-related CS or HF-CS). RESULTS: Among 6,205 patients, 754 received an Impella 5.0/5.5 (12.1%), including 210 MI-CS (27.8%) and 484 HF-CS (64.1%) patients. Impella 5.0/5.5 was used as the sole tMCS device in 32% of patients, while 68% of patients received a combination of tMCS devices. Impella cannulation sites were available for 524/754 (69.4%) of patients, with 93.5% axillary configuration. Survival to hospital discharge for those supported with an Impella 5.0/5.5 was 67%, with 20.4% NHR and 45.5% HRT. Compared to HF-CS, patients with MI-CS supported on Impella 5.0/5.5 had higher in-hospital mortality (45.2% vs 26.2%, p < 0.001) and were less likely to receive HRT (22.4% vs 56.6%, p < 0.001. For patients receiving a combination of tMCS during hospitalization, this was associated with higher rates of limb ischemia (9% vs. 3%, p < 0.01), bleeding (52% vs 33%, p < 0.01), and mortality (38% vs 25%; p < 0.001) compared to Impella 5.0/5.5 alone. Among Impella 5.0/5.5 recipients, the median duration of pump support was 12.9 days (IQR: 6.8-22.9) and longer in patients bridged to HRT (14 days; IQR: 7.7-28.4). CONCLUSIONS: In this multi-center cohort of patients with CS, use of Impella 5.0/5.5 was associated with an overall survival of 67.1% and high rates of HRT. Lower adverse event rates were observed when Impella 5.0/5.5 was the sole support device used. Further study is required to determine whether a strategy of early Impella 5.0/5.5 use for CS improves survival. CONDENSED ABSTRACT: High capacity Impella heart pumps are capable of provide up to 5.5 liter/min of flow while upper body surgical placement allows for ambulation. Patients with advanced cardiogenic shock from acute myocardial infarction or heart failure requiring temporary mechanical circulatory support may benefit from upfront use of Impella 5.5 to improve overall survival, including native heart recovery or successful bridge to durable left ventricular assist device surgery or heart transplantation.

Factors associated with acute limb ischemia in cardiogenic shock and downstream clinical outcomes: Insights from the Cardiogenic Shock Working Group.

BACKGROUND: There are limited data depicting the prevalence and ramifications of acute limb ischemia (ALI) among cardiogenic shock (CS) patients. METHODS: We employed data from the Cardiogenic Shock Working Group (CSWG), a consortium including 33 sites. We constructed a multi-variable logistic regression to examine the association between clinical factors and ALI, we generated another logistic regression model to ascertain the association of ALI with mortality. RESULTS: There were 7,070 patients with CS and 399 (5.6%) developed ALI. Patients with ALI were more likely to be female (40.4% vs 29.4%) and have peripheral arterial disease (13.8% vs 8.3%). Stratified by maximum society for cardiovascular angiography & intervention (SCAI) shock stage, the rates of ALI were stage B 0.0%, stage C 1.8%, stage D 4.1%, and stage E 10.3%. Factors associated with higher risk for ALI included: peripheral vascular disease OR 2.24 (95% CI: 1.53-3.23; p < 0.01) and ≥2 mechanical circulatory support (MCS) devices OR 1.66 (95% CI: 1.24-2.21, p < 0.01). ALI was highest for venous-arterial extracorporeal membrane oxygenation (VA-ECMO) patients (11.6%) or VA-ECMO+ intra-aortic balloon pump (IABP)/Impella CP (16.6%) yet use of distal perfusion catheters was less than 50%. Mortality was 38.0% for CS patients without ALI but 57.4% for CS patients with ALI. ALI was significantly associated with mortality, adjusted OR 1.40 (95% CI 1.01-1.95, p < 0.01). CONCLUSIONS: The rate of ALI was 6% among CS patients. Factors most associated with ALI include peripheral vascular disease and multiple MCS devices. The downstream ramifications of ALI were dire with a considerably higher risk of mortality.

Long-term outcomes for pediatric heart transplant recipients transitioning to adult care teams.

BACKGROUND: There are limited data evaluating the success of a structured transition plan specifically for pediatric heart transplant (HT) recipients following their transfer of care to an adult specialist. We sought to identify risk factors for poor adherence, graft failure, and mortality following the transfer of care to adult HT care teams. METHODS: We retrospectively reviewed all patients who underwent transition from the pediatric to adult HT program at our center between January 2011 and June 2021. Demographic characteristics, comorbid conditions, and psychosocial history were collected at the time of HT, the time of transition, and the most recent follow-up. Adverse events including mortality, graft rejection, infection, and renal function were also captured before and after the transition. RESULTS: Seventy-two patients were identified (54.1% male, 54.2% Caucasian). Mean age at the time of transition was 23 years after a median of 11.6 years in the pediatric program. The use of calcineurin inhibitors was associated with reduced mortality (HR .04, 95% CI .0-.6, p = .015), while prior psychiatric hospitalization (HR 45.3, 95% CI, 6.144-333.9, p = .0001) was associated with increased mortality following transition. Medication nonadherence and young age at the time of transition were markers for high-risk individuals prior to the transition of care. CONCLUSIONS: Transition of HT recipients from a pediatric program to an adult program occurs during a vulnerable time of emerging adulthood, and we have identified risk factors for mortality following transition. Development of a formalized transition plan with a large multidisciplinary team with focused attention on high-risk patients, including those with psychiatric comorbidities, may favorably influence outcomes.

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

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

Hemodynamic Optimization by Invasive Ramp Test in Patients Supported With HeartMate 3 Left Ventricular Assist Device.

In patients supported by the HeartMate 3 left ventricular assist device (HM3 LVAD), pump speed adjustments may improve hemodynamics. We investigated the hemodynamic implications of speed adjustments in HM3 recipients undergoing hemodynamic ramp tests. Clinically stable HM3 recipients who underwent routine invasive hemodynamic ramp tests between 2015 and 2022 at our center were included. Filling pressure optimization, defined as central venous pressure (CVP) <12 mm Hg and pulmonary capillary wedge pressure (PCWP) <18 mm Hg, was assessed at baseline and final pump speeds. Patients with optimized pressures were compared to nonoptimized patients. Overall 60 HM3 recipients with a median age of 62 years (56, 71) and time from LVAD implantation of 187 days (124, 476) were included. Optimized filling pressures were found in 35 patients (58%) at baseline speed. Speed was adjusted in 84% of the nonoptimized patients. Consequently, 39 patients (65%) had optimized pressures at final speed. There were no significant differences in hemodynamic findings between baseline and final speeds ( p > 0.05 for all). Six and 12 month readmission-free rates were higher in optimized compared with nonoptimized patients ( p = 0.03 for both), predominantly due to lower cardiac readmission-free rates ( p = 0.052). In stable outpatients supported with HM3 who underwent routine ramp tests, optimized hemodynamics were achieved in only 2 of 3 of the patients. Patients with optimized pressures had lower all-cause readmission rates, primarily driven by fewer cardiac-related hospitalizations.