Villavicencio, Mauricio A.

ABSTRACT Introduction Improving organ preservation is essential for expanding the donor pool and enhancing outcomes for pediatric transplant recipients. This report presents three pediatric patients who received donor hearts preserved using the Organ Care System (OCS). All donor hearts were prepared, placed, and monitored on OCS according to standard protocols. Heart function and myocardial edema were visually assessed during monitoring. Case Reports Patient 1: A 17‐year‐old female patient with hypertrophic cardiomyopathy utilized OCS technology due to donor distance. She experienced an uncomplicated post‐transplant course and was discharged on post‐transplant day 10. Patient 2: A 14‐year‐old male patient with complex congenital heart disease, palliated with Fontan circulation, underwent orthotopic heart transplantation (OHT) with OCS support due to both the complexity of the procedure and donor heart distance. His post‐transplant course was complicated by a revision of the ascending aorta anastomosis and prolonged milrinone infusion for diastolic dysfunction. He was discharged on post‐transplant day 31. Patient 3: A 16‐year‐old male patient with hypoplastic left heart syndrome, also palliated with Fontan circulation, underwent OHT using OCS technology due to the complexity of the surgical procedure. His post‐transplant recovery was unremarkable, and he was discharged on post‐transplant day 15. Conclusions All three pediatric patients demonstrated favorable short‐term outcomes using OCS technology. The OCS system facilitated shorter ischemic times despite the need for extended transport distances or complex surgical procedures. However, further studies with larger patient cohorts and longer follow‐up are needed to better understand the long‐term impact of OCS on pediatric heart transplantation outcomes.

Abstract The expanding use of continuous‐flow left ventricular assist devices (CF‐LVADs) for end‐stage heart failure warrants familiarity with the physiologic interaction of the device with the native circulation. Contemporary devices utilize predominantly centrifugal flow and, to a lesser extent, axial flow rotors that vary with respect to their intrinsic flow characteristics. Flow can be manipulated with adjustments to preload and afterload as in the native heart, and ascertainment of the predicted effects is provided by differential pressure‐flow ( H ‐ Q ) curves or loops. Valvular heart disease, especially aortic regurgitation, may significantly affect adequacy of mechanical support. In contrast, atrioventricular and ventriculoventricular timing is of less certain significance. Although beneficial effects of device therapy are typically seen due to enhanced distal perfusion, unloading of the left ventricle and atrium, and amelioration of secondary pulmonary hypertension, negative effects of CF‐LVAD therapy on right ventricular filling and function, through right‐sided loading and septal interaction, can make optimization challenging. Additionally, a lack of pulsatile energy provided by CF‐LVAD therapy has physiologic consequences for end‐organ function and may be responsible for a series of adverse effects. Rheological effects of intravascular pumps, especially shear stress exposure, result in platelet activation and hemolysis, which may result in both thrombotic and hemorrhagic consequences. Development of novel solutions for untoward device‐circulatory interactions will facilitate hemodynamic support while mitigating adverse events. © 2021 American Physiological Society. Compr Physiol 12:1‐37, 2021.

Abstract Heart transplantation (HT) is one of the prodigious achievements in modern medicine and remains the cornerstone in the treatment of patients with advanced heart failure. Advances in surgical techniques, immunosuppression, organ preservation, infection control, and allograft surveillance have improved short‐ and long‐term outcomes thereby contributing to greater clinical success of HT. However, prolonged allograft and patient survival following HT are still largely restricted by the development of late complications, including allograft rejection, infection, cardiac allograft vasculopathy (CAV), and malignancy. The introduction of mTOR inhibitors early after HT has demonstrated multiple protective effects against CAV progression, renal dysfunction, and tumorigenesis. Therefore, several HT programs increasingly use mTOR inhibitors with partial or complete withdrawal of calcineurin inhibitor (CNI) in stable HT patients to reduce complications risk and improve long‐term outcomes. Furthermore, despite a substantial improvement in exercise capacity and health‐related quality of life after HT as compared to advanced heart failure patients, most HT recipients remain with a 30% to 50% lower peak oxygen consumption (Vo 2 ) than that of age‐matched healthy subjects. Several factors, including alterations in central hemodynamics, HT‐related complications and alterations in the musculoskeletal system, and peripheral physiological abnormalities, presumably contribute to the reduced exercise capacity following HT. Cardiac denervation and subsequent loss of sympathetic and parasympathetic regulation are responsible for various physiological alterations in the cardiovascular system, which contributes to restricted exercise tolerance. Restoration of cardiac innervation may improve exercise capacity and quality of life, but the reinnervation process is only partial even several years after HT. Multiple studies have shown that aerobic and strengthening exercise interventions improve exercise capacity by increasing maximal heart rate, chronotropic response, and peak Vo 2 after HT. Novel exercise modalities, such as high‐intensity interval training (HIT), have been proven as safe and effective for further improvement in exercise capacity, including among de novo HT recipients. Further developments have recently emerged, including donor heart preservation techniques, noninvasive CAV and rejection surveillance methods, and improvements in immunosuppressive therapies, all aiming at increasing donor availability and improving late survival after HT. © 2023 American Physiological Society. Compr Physiol 13:4719‐4765, 2023.

ABSTRACT Background Addition of left heart catheterization (LHC) to exercise protocols allows for a unique focus on parameters of systolic and diastolic responses to increased activity in patients with left ventricular assist device (LVAD) support. Methods A retrospective review was conducted of all consecutive adult patients who underwent LHC with exercise for any indication from June 2017 to June 2023. For all patients, the relationship between exercise and parameters of LV systolic and diastolic response was assessed. Patients were divided into two cohorts based on the indication for testing: hemodynamic optimization (Optim, n = 5) or weaning consideration (Wean, n = 3). Results Eight patients (88% male, median age 57 years (IQR 44, 65)) were included. LVEF was 45% (IQR 45, 56) in Wean and 25% (IQR 20, 42) in Optim. LV systolic work index (LVSWI) increased more rapidly over levels of exercise in Wean vs. Optim (slope 46.3 vs. −0.625; p = 0.044) and LVSWI rose more quickly at lower levels of LV end diastolic pressure (LVEDP) in Wean vs. Optim (slope 219.5 vs. −2.008; p = 0.0026). Pulse power index was higher in Wean patients at baseline (0.046 (IQR 0.04, 0.07) vs. 0.016 (IQR 0.001, 0.04); p = 0.14) and peak exercise (0.12 (IQR 0.12, 0.12) vs. 0.06 (IQR 0.03, 0.1); p = 0.29). Conclusions Patients with favorable remodeling on LVAD support have significantly improved LV systolic and diastolic responses to exercise and a trend of higher systemic pulsatility. Improving our understanding of LV‐LVAD interactions with activity may aid in future efforts to improve exercise tolerance through speed modulation.

BACKGROUND: A preservation system, the Organ Care System (OCS; TransMedics) uses normothermic pulsatile perfusion during organ transport for heart transplantation. This system has demonstrated favorable outcomes in hearts recovered from extended-criteria donors after brain death (DBD) and donors after circulatory death (DCD). METHODS: The OCS Heart Perfusion Registry collects data on US heart transplantations using the OCS, static cold storage (SCS), or thoracoabdominal normothermic regional perfusion (NRP) and donor hearts recovered from DBD or DCD donors. We analyzed donor and recipient characteristics and posttransplantation outcomes in patients transplanted with OCS donor hearts (either DBD or DCD) compared with SCS hearts, and with OCS hearts from DCD donors compared with those recovered with NRP followed by SCS. Propensity score matching was used in survival analyses to adjust for differences among recipient characteristics. RESULTS: Between 2021 and 2023, 3225 consecutive heart transplantations enrolled from 56 centers were analyzed in the Heart Perfusion Registry. The OCS was used in 854 of 3225 heart transplantations (26.4%), among which 340 (39.8%) were DBD and 514 (60.2%) were DCD donors, whereas 2174 DBD donors were recovered with SCS and another 197 DCD donors with NRP techniques. The OCS-DBD group experienced a greater number of organ offer refusals before final acceptance (13 versus 6; Wilcoxon rank sum, P <0.001) and a longer transport distance (667 miles versus 232 miles; Wilcoxon rank sum, P <0.001) compared with SCS-DBD. Survival at 12 months was similar between the 2 groups (89.9% for OCS-DBD versus 90.6% for SCS-DBD; marginal Cox model, P =0.54). Among the OCS-DCD and SCS-DBD groups, survival at 12 months was also similar (91.0% versus 92.5%, respectively; marginal Cox model, P =0.32). The OCS-DCD and NRP-DCD groups demonstrated similar survival (91.0% versus 91.7%, respectively; log rank, P =0.63), although the transport distance was longer in OCS-DCD compared with DCD with NRP followed by SCS (400 miles versus 223 miles; Wilcoxon rank sum, P <0.001). By 2023, 90% of all OCS donor management and recovery was performed with dedicated organ recovery teams. CONCLUSIONS: We demonstrate that real-world implementation of the OCS for DBD donors (using predominantly a dedicated recovery team) is associated with expanded donor criteria, longer transport distance, and excellent posttransplantation outcomes. In OCS-DCD donors, outcomes parallel those of donors recovered with NRP-DCD and compare favorably with DBD donor organs.

Abstract Introduction Cardiopulmonary exercise testing (CPET) parameters such as peak VO2 ≤ 14ml/kg/min, percentage predicted peak VO2 (ppVO2) ≤ 50% and ventilation equivalent of carbon dioxide (Ve/VCO2) &gt;35 l/min/l/min are recommended thresholds to list for isolated heart transplant. There is minimal data on clinical events after listing to guide clinical management or priority in organ allocation. Purpose To assess the effect of peak VO2, ppVO2, Ve/VCO2 on clinical events after listing for isolated heart transplant. Methods In a single centre retrospective study, we identified patients who were status 6 or status 2 prior to 2018 at time of listing for isolated heart transplant between 2007 and 2021. Clinical data were collected by chart review. Primary outcome of progressive heart failure was defined as death or upgrade in transplant priority status (new inotropes or mechanical circulatory support). Comparison was made between peak VO2 strata (&gt; 14 vs ≤ 14 ml/kg/min), ppVO2 strata (&gt; 50% vs 40-50% vs &lt;40%) and Ve/VCO2 strata (&lt;35 vs &gt;35 l/min/l/min). Secondary outcome was time dependent survival after listing for heart transplant. Results We identified 141 patients of which 133 underwent CPET and follow up was available for 130 who were included in the analysis. Median age was 53 years (interquartile range 41-59 years), 29.1% of patients were female. Median peak VO2 was 14.0 ml/kg/min (11.2-15.7), ppVO2 was 44% (36-52), Ve/VCO2 slope was 34.0 (31.0-37.0) and RER was 1.1 (1.1-1.2). 87 patients had progressive heart failure consisting of 34 deaths and 83 patients having upgrade in priority status. There was a significant difference in risk of progressive heart failure comparing peak VO2 strata (Figure 1) (freedom from event at one year 71.4% with peak VO2 &gt; 14 vs 46.5% with peak VO2 ≤ 14, p=0.00061) and ppVO2 strata (Figure 2) (freedom from event at one year 75.0% with ppVO2 &gt;50% vs 61.2% with ppVO2 40-50% vs 42.6% with ppVO2 &lt;40%, p=0.0015). There was no significant difference with Ve/VCO2 strata (freedom from event at one year 59.8% with Ve/VCO2 &lt;34 vs 54.9% with Ve/VCO2 &gt;34, p=0.52). There were 34 deaths before transplant and 23 deaths after transplant. 87 patients underwent transplant. In a time dependent survival analysis, age, gender and ppVO2&lt;50% (HR 1.65 (0.87-3.12)) were not significant predictors of mortality. Both early transplant (defined as &lt; 1 year after listing, HR 0.14 (0.06-0.34) and late transplant (defined as &gt; 1 year after listing, HR 0.16 (0.08-0.32)) were significant predictors of lower mortality whilst Ve/VCO2&gt;35 (HR 2.09 (1.19-3.68)) was a significant predictor of higher mortality. Conclusions Peak VO2 and ppVO2 stratify risk of progressive heart failure in ambulatory patients awaiting isolated heart transplant. However, Ve/VCO2 is a predictor of significantly higher mortality. These findings should affect clinical management and transplant priority status; and influence revision of future guidelines.Freedom from event by peak VO2 strataFreedom from event by ppVO2 strata

Background Transplantation using hearts obtained through donation after circulatory death (DCD) is increasing, but data on recipient renal outcomes are limited. Methods and Results Patients at a single institution who underwent heart transplantation using organs procured through DCD or donation after brain death (DBD) from April 2016 to August 2022 were included in this retrospective cohort study. Hemodynamic measures were collected via right heart catheterization performed 1 week after transplantation. Posttransplantation renal outcomes included estimated glomerular filtration rate at 1 week, 4 weeks, and 16 weeks, and the incidence of acute kidney injury (AKI) and renal replacement therapy within 1 week. The analysis included 225 patients (55 recipients of DCD). Baseline characteristics were comparable between recipients of DCD and DBD. Renal outcomes within 1 week posttransplantation in recipients of DCD were similar to recipients of DBD, including percent change in estimated glomerular filtration rate (−37.9% [−58.6 to −6.2] versus −31.9% [−52.4 to −9.9]; P =0.91), incidence of AKI (47.3% versus 46.5%; P >0.99) and incidence of renal replacement therapy (3.6% versus 4.7%; P >0.99). Recipients of DCD with AKI within 1 week (“early AKI”) did not recover to baseline estimated glomerular filtration rate (75.8 [60.2–91.3] mL/min per 1.73 m 2 ) by week 16 (59.3 [46.9–73.6] mL/min per 1.73 m 2 ; P =0.002), whereas recipients without early AKI exhibited comparable estimated glomerular filtration rate to baseline by week 4 (84.5 [70.8–98.5] mL/min per 1.73 m 2 ; P =0.084). Similar trends were observed in recipients of DBD. Conclusions Recipients of DCD demonstrated similar renal outcomes compared with recipients of DBD, supporting the ongoing use of DCD transplantation. Early AKI was associated with persistent renal dysfunction for recipients of both DCD and DBD.

ABSTRACTIntroductionLung transplantation has become increasingly utilized in patients with COVID‐19. While several single‐center and UNOS database studies have been published on lung transplants (LTs) for end‐stage lung disease (ESLD) from Coronavirus disease 2019 (COVID‐19), there is a lack of multi‐center and international data.MethodsThis is a multicenter analysis from 11 high‐volume lung transplant centers in the United States and Europe. Data were collected through the Multi‐Institutional ECLS Registry and stratified by ESLD due to COVID‐19 versus other etiologies. Demographics and clinical variables were compared using Chi‐square test and Fisher's exact test. Survival was assessed by Kaplan‐Meier curves and compared by log‐rank test with propensity score matching.ResultsOf 1606 lung transplant recipients, 46 (2.9%) were transplanted for ESLD from COVID‐19 compared to 1560 (97.1%) without a history of COVID‐19. Among COVID‐19 patients, 30 (65.2%) had COVID‐19‐associated ARDS and 16 (34.8%) had post‐COVID‐19 fibrosis. COVID‐19 patients had higher lung allocation scores (78.0 vs. 44.4, p < 0.0001), had severely limited functional status (37.0% vs. 2.9%, p < 0.0001), had higher preoperative ECMO usage (65.2% vs. 5.4%, p < 0.0001), and spent less time on the waitlist (32 vs. 137 days, p < 0.0001). A 30‐day survival was comparable between COVID‐19 and non‐COVID‐19 patients before (100% vs. 98.7%, p = 0.39) and after propensity matching (p = 0.15).ConclusionsPatients who received LTs due to COVID‐19 had short‐term survival comparable to that of patients without COVID‐19. Our findings support the idea that lung transplantation should be considered for select patients with ESLD due to COVID‐19.

ABSTRACTBackgroundEvolving trends in organ procurement and technological innovation prompted an investigation into recent trends, indications, and outcomes following combined heart–lung transplantation (HLTx).MethodsThe United Network for Organ Sharing database was queried for all adult (≥18 years) HLTx performed between July 1, 2013 and June 30, 2023. Patients with previous transplants were excluded. The primary endpoint was the effect of donor, recipient, and transplantation characteristics on 1‐ and 5‐year survival. Secondary analyses included a comparison of HLTx at high‐ and low‐volume centers, an assessment of HLTx following donation after circulatory death (DCD), and an evaluation of HLTx volume over time. Cox proportional‐hazards models were used to assess factors associated with mortality. Temporal trends were evaluated with linear regression.ResultsAfter exclusions, 319 patients were analyzed, of whom 5 (1.6%) were DCD. HLTx volume increased from 2013 to 2023 (p < 0.001). One‐ and 5‐year survival following HLTx was 84.0% and 59.5%, respectively. One‐year survival was higher for patients undergoing HLTx at a high‐volume center (88.3% vs. 77.9%; p = 0.012). After risk adjustment, extracorporeal membrane oxygenation support 72 h posttransplant and predischarge dialysis were associated with increased 1‐year mortality (HR = 3.19, 95% CI = 1.86–5.49 and HR = 3.47, 95% CI = 2.17–5.54, respectively) and 5‐year mortality (HR = 2.901, 95% CI = 1.679–5.011 and HR = 3.327, 95% CI = 2.085–5.311, respectively), but HLTx at a high‐volume center was not associated with either.ConclusionsHLTx volume has resurged, with DCD HLTx emerging as a viable procurement strategy. Factors associated with 1‐ and 5‐year survival may be used to guide postoperative management following HLTx.

Axillary artery intra-aortic balloon pump (axIABP) placement has been implemented as a bridging solution before heart transplantation. This study evaluates complications associated with axIABP support and describes an approach to minimize adverse events. We previously described a percutaneous approach for axIABP placement. However, patients receiving axIABP between September 1, 2017, and September 26, 2019 (n = 32) demonstrated a high rate of balloon pump malfunction (8/32; 25%) and other complications (totaling 15/32; 47%). Sixty-four patients were sequentially treated under a revised protocol. Compared to the initial cohort, no significant differences in demographics were noted. A significant reduction in rate of balloon malfunction (8/32, 25% vs. 1/64, 2%; p < 0.001) and total complications (15/32, 47% vs. 10/64, 16%; p = 0.0025) during the period of support were noted after intervention. Subsequent analysis of total complications per device size (40 vs. ≤ 34 ml balloon) revealed significantly reduced complications in patients with smaller devices (40% vs. 13%, respectively; p = 0.0022). This study provides guidelines to limit complications in patients supported with axIABP, facilitating a protracted period of bridging support.