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Introduction: Clinical success of donation after circulatory death (DCD) heart transplantation is leading to growing adoption of this technique. In comparison to procurement from a brain‐dead donor, DCD requires additional resources. The economic impact of DCD heart transplantation from the hospital perspective is not well known. Methods: We compared the financial data of patients who received DCD allografts to those who received a DBD organ at our institution from January 1, 2021 to December 31, 2022. We also compared the cost of ex‐situ machine perfusion to in‐situ organ perfusion employed during DCD recovery. Results: We performed 58 DBD and 22 DCD heart‐alone transplantations during the study period. Out of 22 DCD grafts, 16 were recovered with thoracoabdominal normothermic regional perfusion (TA‐NRP) and six with direct procurement followed by normothermic machine perfusion (DP‐NMP). The contribution margin per case for DBD versus DCD was $234,362 and $235,440 (P =.72). The direct costs did not significantly differ between the two groups ($171,949 and 186,250; P =.49). In comparing the two methods of procuring hearts from DCD donors, the direct cost of TA‐NRP was $155,955 in comparison to $223,399 for DP‐NMP (P =.21). This difference translated into a clinically meaningful but not statistically significant greater contribution margin for TA‐NRP ($242, 657 vs. $175,768; P =.34). Conclusions: Our data showed that the adoption of DCD procurement did not have a negative financial impact on the contribution margin in our institution. Programs considering starting DCD heart transplantation, and those who are currently performing DCD procurement should evaluate their own financial situation. [ABSTRACT FROM AUTHOR]

Introduction: Donation after circulatory death (DCD) heart transplantation has been shown to have comparable outcomes to transplantation using brain death donors (DBDs). This study evaluates the impact of this alternative source of allografts on waitlist mortality and transplant volume. Methods: We compared waitlist mortality and transplant rates in patients who were registered before (2019 period) and after we adopted DCD heart transplantation (2021 period). Results: We identified 111 patients who were on the waiting list in 2019 and 77 patients who were registered during 2021. Total number of donor organ offers received in 2019 was 385 (178 unique donors) versus 3450 (1145 unique donors) in 2021. More than 40% of all donors in 2021 were DCDs. Waitlist mortality was comparable for patients in 2019 and 2021 (18/100 person‐years in 2019 vs. 26/100 person‐years in 2021, p =.49). The transplant rate was 67/100 person‐years in 2019 versus 207/100 person‐years in 2021 (p <.001). After adjusting for acuity status, gender, blood type, and weight, patients listed in 2021 had 2.08 times greater chance of transplantation compared to patients listed in 2019 (HR 2.08, 95% confidence interval [CI] 1.26–3.45, p =.004). Conclusions: Use of DCD donor hearts significantly increased heart transplant rate in our institution. [ABSTRACT FROM AUTHOR]

Background: In complex operations surgeon volume may impact outcomes. We sought to understand if individual surgeon volume affects left ventricular assist device (LVAD) outcomes.Methods: We reviewed primary LVAD implants at an experienced ventricular assist devices (VAD)/transplant center between 2013 and 2019. Cases were dichotomized into a high-volume group (surgeons averaging 11 or more LVAD cases per year), and a low-volume group (10 or less per year). Propensity score matching was performed. Survival to discharge, 1-year survival, and incidence of major adverse events were compared between the low- and high-volume groups. Predictors of survival were identified with multivariate analysis.Results: There were 315 patients who met inclusion criteria-45 in the low-volume group, 270 in the high-volume group. There was no difference in survival to hospital discharge between the low (91.9%) and high (83.3%) volume matched groups (p = .22). Survival at 1-year was also similar (85.4% vs. 80.6%, p = .55). There was no difference in the incidence of major adverse events between the groups. Predictors of mortality in the first year included: age (hazards ratio [HR]: 1.061, p < .001), prior sternotomy (HR: 1.991, p = .01), increasing international normalized ratio (HR: 4.748, p < .001), increasing AST (HR: 1.001, p < .001), increasing bilirubin (HR: 1.081, p = .01), and preoperative mechanical ventilation (HR: 2.662, p = .005). Individual surgeon volume was not an independent predictor of discharge or 1-year survival.Conclusion: There was no difference in survival or adverse events between high and low volume surgeons suggesting that, in an experienced multidisciplinary setting, low-volume VAD surgeons can achieve similar outcomes to their high-volume colleagues. [ABSTRACT FROM AUTHOR]

Although temporary mechanical circulatory support (tMCS) for hemodynamic failure following heart transplantation is associated with increased early morbidity and mortality, the impact of etiology of graft dysfunction and long‐term clinical implications are less well known. The objective of our study was to evaluate outcomes in patients who required venoarterial extracorporeal membrane oxygenation (VA ECMO) or temporary right ventricular assist device (RVAD) support for either primary or secondary early graft dysfunction. Hospital mortality in 27 patients who required tMCS following heart transplantation at our institution between 2007 and 2017 was 56%, 30% in patients with right ventricular dysfunction secondary to increased afterload, 60% in patients with primary graft dysfunction, and 100% in patients with graft failure secondary to coagulopathy with intraoperative bleeding or overwhelming sepsis. Conditional 1‐year and 5‐year survival was comparable between patients with, and without, the need for post‐transplantation support with tMCS (98% and 89%; 92% and 65% at 1 and 5 years, P =.21). Etiology of early graft failure plays an important part in determining the short‐term post–heart transplantation outcome. Although complications associated with tMCS use, such as renal dysfunction and infection, extend beyond index transplant hospitalization, long‐term conditional survival is not compromised. [ABSTRACT FROM AUTHOR]

Background: Several patient-related characteristics have been associated with inferior outcomes following durable left ventricular assist device (LVAD) implantation in patients transitioned from venoarterial extracorporeal membrane oxygenation (VA ECMO). The impact of LVAD pump type used is less well-known.Methods: We compared outcomes between patents who received axial and centrifugal flow LVADs following stabilization with VA ECMO.Results: From January 2011 to December 2018, we implanted 28 LVADs in patients transitioned from VA ECMO. This included 17 axial flow devices (HeartMate II LVAD, Abbott Laboratories, Chicago, IL) and 11 centrifugal flow pumps (eight HeartWare HVADs; Medtronic, Minneapolis, MN and three HeartMate 3 LVAS pumps; Abbott Laboratories, Chicago, IL). There was no difference in hospital mortality (23.5% vs 18.2%, P = .74) or 1-year survival (P = .31) between the devices. There were no differences in adverse event rates between the two pump types, apart from a higher rate of gastrointestinal bleeding in patients who received centrifugal flow pumps (1.44 events per 100 patient-months vs 14.67 events per 100 patient-months, P = .010). Preimplantation levels of alanine aminotransferase (hazard ratio [HR], 1.001; 95% confidence interval [CI], 1.000 to 1.002; P = .004) and elevated serum creatinine level (HR, 3.480; 95% CI, 1.121-10.807; P = .031) emerged as significant predictors of decreased 1-year survival.Conclusions: Preimplantation optimization of end-organ function is the single most important determinant of successful post-LVAD survival in patients transitioned from extracorporeal life support. There is no association of pump type with LVAD outcomes up to 1-year post implantation. [ABSTRACT FROM AUTHOR]

Background Sinus tachycardia ( ST) is common after heart transplantation ( HTx). The aim of the study was to evaluate the effect of diltiazem treatment during the first year after HTx on heart rate ( HR), cardiac allograft function, and exercise capacity. Methods From the total cohort, 25 HTx recipients started diltiazem treatment 4±2 weeks after HTx and continued it for at least 1 year (diltiazem group). Each study case was matched to a control. All patients underwent hemodynamic assessment and cardiopulmonary exercise test ( CPET) at 1 year after HTx. Results HR decreased in the diltiazem group from 99±11 bpm to 94±7 bpm ( P=.03) and did not change in the controls (98±11 bpm vs 100±13 bpm, P=.14). The difference between the groups at 1 year after HTx was significant ( P=.04). In the diltiazem group left ventricular ( LV), stroke volume and ejection fraction increased (48±16 vs 55±17 mL, P=.02, and 60%±10% vs 62%±12% P=.03, respectively) but did not differ from controls. E/E' decreased (10.7±2.7 vs 7.3±1.9, P=.003) while cardiac index was higher (3.5±0.8 vs 3.1±0.5; P=.05) in the diltiazem group at 1-year follow-up. The absolute peak VO2 (21±4 vs 18±6 mL/kg/min; P=.05) and normalized peak VO2 (73%±17% vs 58%±14%; P=.004) were significantly higher in the diltiazem group. Conclusions This study showed that diltiazem treatment reduces ST, may improve cardiac allograft function and exercise tolerance during the first year after HTx. [ABSTRACT FROM AUTHOR]

Background Sinus tachycardia often presents in heart transplantation ( HTx) recipients, but data on its effect on exercise performance are limited. Methods Based on mean heart rate ( HR) value 3 months after HTx, 181 patients transplanted from 2006 to 2015 at University of Nebraska Medical Center were divided into two groups: (i) HR<95 beats/min (bpm, n=93); and (ii) HR≥95 bpm (n=88). Cardiopulmonary exercise testing ( CPET) was performed 1 year after HTx. Results Mean HR at 3 months post- HTx was 94±11 bpm and did not change significantly at 1 year post- HTx (96±11 bpm, P=.13). HR≥95 bpm at 3 months was associated with younger donor age ( OR 1.1; CI 1.0-1.1, P=.02), female donors ( OR −2.4; CI 1.16-5.24 P=.02), and lack of donors' heavy alcohol use ( OR −0.43; CI 0.17-0.61; P=.04). HR≥95 bpm at 3 months post- HTx was independently associated with decreased exercise capacity in metabolic equivalent ( P=.008), reduced peak VO2 ( P=.006), and percent of predicted peak VO2 ( P=.002) during CPET. Conclusions HR≥95 at 3 months following HTx is associated with reduced exercise tolerance in stable HTx recipients. Medical HR reduction after HTx could improve exercise performance after HTx and merits further investigation. [ABSTRACT FROM AUTHOR]

The article discusses results of a study on the novel use of mobile ex-vivo lung perfusion (EVLP) in donation after circulatory death (DCD) lung transplantation.

Background: Myocardial recovery with left ventricular assist device (LVAD) therapy is highly variable and difficult to predict. Next generation ribonucleic acid (RNA) sequencing is an innovative, rapid, and quantitative approach to gene expression profiling in small amounts of tissue. Our primary goal was to identify baseline transcriptional profiles in non-ischemic cardiomyopathies that predict myocardial recovery in response to LVAD therapy. We also sought to verify transcriptional differences between failing and non-failing human hearts. Methods: RNA was isolated from failing (n = 16) and non-failing (n = 8) human hearts. RNA from each patient was reverse transcribed and quantitatively sequenced on the personal genome machine (PGM) sequencer (Ion torrent) for 95 heart failure candidate genes. Coverage analysis as well as mapping the reads and alignment was done using the Ion Torrent Browser Suite™. Differential expression analyses were conducted by empirical analysis of digital gene expression data in R (edgeR) to identify differential expressed genes between failing and non-failing groups, and between responder and non-responder groups respectively. Targeted cardiac gene messenger RNA (mRNA) expression was analyzed in proportion to the total number of reads. Gene expression profiles from the PGM sequencer were validated by performing RNA sequencing (RNAseq) with the Illumina Hiseq2500 sequencing system. Results: The failing sample population was 75% male with an average age of 50 and a left ventricular ejection fraction (LVEF) of 16%. Myosin light chain kinase (MYLK) and interleukin (IL)-6 genes expression were significantly higher in LVAD responders compared to non-responders. Thirty-six cardiac genes were expressed differentially between failing and non-failing hearts (23 decreased, 13 elevated). MYLK, Beta-1 adrenergic receptor (ADRB1) and myosin heavy chain (MYH)-6 expression were among those significantly decreased in failing hearts compared to non-failing hearts. Natriuretic peptide B (NPPB) and IL-6 were significantly elevated. Targeted gene expression profiles obtained from the Ion torrent PGM sequencer were consistent with those obtained from Illumina HiSeq2500 sequencing system. Conclusions: Heart failure is associated with a network of transcriptional changes involving contractile proteins, metabolism, adrenergic receptors, protein phosphorylation, and signaling factors. Myocardial MYLK and IL-6 expression are positively correlated with ejection fraction (EF) response to LVAD placement. Targeted RNA sequencing of myocardial gene expression can be utilized to predict responders to LVAD therapy and to better characterize transcriptional changes in human heart failure. [ABSTRACT FROM AUTHOR]

Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend against the use of hearts from donors that abuse alcohol. We explored the effect of donor alcohol abuse (AA) on cardiac allograft function and outcomes in heart transplant (HTx) recipients. Methods: Overall, 370 HTx recipients were divided into two groups: (a) the alcoholic donor group (AD, n = 58) and (b) the non‐alcoholic donor group (NAD, n = 312). Results: Recipients in the AD group had a slower heart rate (86 ± 13 vs 93 ± 13, P = 0.004) and an increased incidence of early atrial fibrillation (AF) (30% vs 11%, P = 0.003). Echocardiographic left ventricular mass was higher among alcoholic donors (171.7 ± 66.7 vs 151.6 ± 54.7, P = 0.02). This difference remained present 1 year following HTx (185 ± 43 vs 166 ± 42, P = 0.007). E/E′ was higher in the AD group (9.5 ± 3.9 vs 8.4 ± 2.9, P = 0.04) and a larger number of AD recipients had a ventilatory equivalent for VCO2 > 34 (50% vs 31%, P = 0.04) on cardiopulmonary exercise test. There was no significant difference in rejection, cardiac allograft vasculopathy (CAV), or survival between the groups. Conclusions: Our data suggest that donor AA does not impact rejection, CAV, or intermediate‐term survival, but may cause increased incidence of post‐HTx AF and impaired cardiac allograft diastolic function. [ABSTRACT FROM AUTHOR]

Background: Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited., Methods: We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation., Results: A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation., Conclusions: In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.)., (Copyright © 2023 Massachusetts Medical Society.)

Lung transplantation with lungs procured from donors after circulatory death (DCD) has been established as an alternative technique to traditional donation after brain death (DBD) with comparable outcomes. Recently, in situ thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a novel technique employed in the procurement of cardiac allografts after circulatory death. TA-NRP, in contrast to ex situ machine perfusion, has the advantage of allowing in situ assessment of donor organs prior to final acceptance. However, there are some concerns that this technique may adversely impact the quality of lung allografts. Here, we present a case of a successful bilateral sequential lung transplantation in a patient with postinflammatory pulmonary fibrosis due to acute respiratory distress syndrome (ARDS), with lungs procured after normothermic in situ lung perfusion. Apart from the lungs, heart, liver, and kidneys were also successfully transplanted from this donor., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: In two interim analyses of this trial, patients with advanced heart failure who were treated with a fully magnetically levitated centrifugal-flow left ventricular assist device were less likely to have pump thrombosis or nondisabling stroke than were patients treated with a mechanical-bearing axial-flow left ventricular assist device., Methods: We randomly assigned patients with advanced heart failure to receive either the centrifugal-flow pump or the axial-flow pump irrespective of the intended goal of use (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or remove a malfunctioning device. The principal secondary end point was pump replacement at 2 years., Results: This final analysis included 1028 enrolled patients: 516 in the centrifugal-flow pump group and 512 in the axial-flow pump group. In the analysis of the primary end point, 397 patients (76.9%) in the centrifugal-flow pump group, as compared with 332 (64.8%) in the axial-flow pump group, remained alive and free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years (relative risk, 0.84; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 for superiority). Pump replacement was less common in the centrifugal-flow pump group than in the axial-flow pump group (12 patients [2.3%] vs. 57 patients [11.3%]; relative risk, 0.21; 95% CI, 0.11 to 0.38; P<0.001). The numbers of events per patient-year for stroke of any severity, major bleeding, and gastrointestinal hemorrhage were lower in the centrifugal-flow pump group than in the axial-flow pump group., Conclusions: Among patients with advanced heart failure, a fully magnetically levitated centrifugal-flow left ventricular assist device was associated with less frequent need for pump replacement than an axial-flow device and was superior with respect to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755.)., (Copyright © 2019 Massachusetts Medical Society.)

Background: Tumor necrosis factor-alpha (TNF-alpha) is a well-documented central inflammatory mediator in sepsis. Specific polymorphisms of the TNF-alpha and TNF-beta genes (TNF2 and LTA + 250, respectively) have been suggested to correlate with higher mortality in septic shock. This study sought to determine whether these polymorphisms of the TNF-alpha and -beta genes are associated with an increased risk of infection in an at-risk surgical intensive care population., Materials and Methods: Forty-four consecutive patients with systemic inflammatory response syndrome were enrolled prospectively in the study. Genomic DNA was isolated from whole blood samples using standard phenol/chloroform extraction techniques. Specific fragments including the polymorphic sites of each gene were amplified by polymerase chain reaction, and restriction enzyme digestions were performed. Genotypes were determined by gel electrophoresis and confirmed by direct sequencing., Results: Eighty-six percent of the patients were TNF1 homozygotes (G:G at -308 of the TNF-alpha promoter region), whereas 9% of the patients were homozygous for TNF2 (A:A). There was no difference in the incidence of sepsis, septic shock, or mortality between patients bearing the various alleles. Only 13.6% of the patients exhibited the G:G alleles for TNF-beta, whereas the homozygous A:A was present in 45.4% of the patients., Conclusion: The presence of the A allele at these polymorphic sites did not predispose critically ill surgical patients to either infection or septic shock.