Financial impact of donation after circulatory death heart transplantation: A single-center analysis.

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.

Ventricular assist device using a thoracotomy-based implant technique: Multi-Center Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy (HM3 SWIFT).

OBJECTIVES: The HeartMate 3 (Abbott) left ventricular assist device provides substantial improvement in long-term morbidity and mortality in patients with advanced heart failure. The Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy study compares thoracotomy-based implantation clinical outcomes with standard median sternotomy. METHODS: We conducted a prospective, multicenter, single-arm study in patients eligible for HeartMate 3 implantation with thoracotomy-based surgical technique (bilateral thoracotomy or partial upper sternotomy with left thoracotomy). The composite primary end point was survival free of disabling stroke (modified Rankin score >3), or reoperation to remove or replace a malfunctioning device, or conversion to median sternotomy at 6-months postimplant (elective transplants were treated as a success). The primary end point (noninferiority, -15% margin) was assessed with >90% power compared with a propensity score-matched cohort (ratio 1:2) derived from the Multi-Center Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 continued access protocol. RESULTS: The study enrolled 102 patients between December 2020 and July 2022 in the thoracotomy-based arm at 23 North American centers. Follow-up concluded in December 2022. In the Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy study group, noninferiority criteria was met (absolute between-group difference, -1.2%; Farrington Manning lower 1-sided 95% CI, -9.3%; P < .0025) and event-free survival was not different (85.0% vs 86.2%; hazard ratio, 1.01; 95% CI, 0.58-2.10). Length of stay with thoracotomy-based implant was longer (median, 20 vs 17 days; P = .03). No differences were observed for blood product utilization, adverse events (including right heart failure), functional status, and quality of life between cohorts. CONCLUSIONS: Thoracotomy-based implantation of the HeartMate 3 left ventricular assist device is noninferior to implantation via standard full sternotomy. This study supports thoracotomy-based implantation as an additional standard for surgical implantation of the HeartMate 3 left ventricular assist device.

Utilization of Paragonix Sherpapak Cardiac Transport System for the Preservation of Donor Hearts After Circulatory Death.

BACKGROUND: Donation after circulatory death (DCD) heart transplantation is being increasingly adopted by transplant centers. The optimal method of DCD heart preservation during transport after in situ thoracoabdominal normothermic regional perfusion (TA-NRP) is not known. METHODS: We evaluated our experience with the Paragonix SherpaPak Cardiac Transport System (SCTS) for the transport of DCD cardiac allografts after TA-NRP recovery between January 2021 and December 2022. We collected and evaluated donor characteristics, allograft ischemic intervals, and recipient baseline demographic and clinical variables, and short-term outcomes. RESULTS: Twelve recipients received DCD grafts recovered with TA-NRP and transported in SCTS during the study period. The median age of 10 male and 2 female donors was 32 years (min 15, max 38). The median duration of functional warm ischemia was 12 minutes (min 8, max 22). Hearts were preserved in SCTS for a median of 158 minutes (min 37, max 224). Median recipient age was 61 years (min 28, max 70). Ten recipients (83%) survived to hospital discharge, with one death attributable to graft dysfunction (8%). The median vasoactive-inotropic (VIS) score at 72 hours post-transplantation of the entire cohort was 6 (min 0, max 15). The median length of intensive care unit stay in hospital survivors was 5 days (min 3, max 17) days and hospital stay 17 days (min 9, max 37). CONCLUSIONS: The Paragonix SCTS provides efficacious preservation of DCD grafts for ≥3.5 hours. Organs transported with this device showed satisfactory post-transplantation function.

Transplantation Outcomes with Donor Hearts after Circulatory Death.

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.).

Impact of donation after circulatory death heart transplantation on waitlist outcomes and transplantation activity.

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.

Cardiac function unchanged following reanimation with normothermic regional perfusion in donation after circulatory death.

Objectives: To determine whether hearts reanimated with normothermic regional perfusion (NRP) have clinically detectable changes in function using echocardiography comparing the prearrest and post-NRP imaging. As heart transplantation from donation after circulatory death (DCD) continues to increase, preliminary results suggest outcomes comparable with donation after brain death. It is unknown whether the obligatory period of warm ischemia experienced during DCD withdrawal process causes immediate changes in cardiac allograft function following in situ reanimation. Methods: We retrospectively reviewed and compared predonation with postreanimation echocardiographic findings in all DCD donors at our institution from January to October 2021. All DCD donor organs were reanimated with in situ thoracoabdominal NRP after circulatory death. Echocardiographic assessment included (1) 2-dimensional and speckle-tracking measures of chamber size and function; (2) ejection fraction; (3) fractional area change; and (4) global longitudinal strain. Results: Altogether, 4 DCD heart donations were performed during the study period. Basic demographics and withdrawal ischemic time periods are reported. There were no changes in left ventricular ejection fraction and right ventricular fractional area change when comparing the predonation and the postreanimation echocardiogram. There was a minimal, nonstatistically significant decrease in left ventricular global longitudinal strain and right ventricular free-wall systolic strain in 3 of the 4 donors following reanimation. Conclusions: DCD cardiac allografts reanimated with NRP demonstrated no change in echocardiographic parameters used for a standard predonation donor heart evaluation. Findings suggest cardiac function of DCD allografts reanimated with thoracoabdominal NRP is not adversely impacted by limited period of warm ischemia following circulatory arrest.

In a large-volume multidisciplinary setting individual surgeon volume does not impact LVAD outcomes.

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.

Thoracoabdominal Normothermic Perfusion in Donation After Circulatory Death.

Donation after circulatory death is emerging as an alternative pathway to donation after brain death to expand the cardiac organ donor pool. We describe the surgical technique and circuit configuration for in-situ organ reperfusion with thoracoabdominal normothermic regional perfusion using portable venoarterial extracorporeal membrane oxygenation.

Successful lung transplantation with graft recovered after thoracoabdominal normothermic perfusion from donor after circulatory death.

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.

Preoperative Right Heart Dysfunction and Gastrointestinal Bleeding in Patients with Left Ventricular Assist Devices.

Gastrointestinal bleeding (GIB) is a common cause of morbidity among patients supported by left ventricular assist devices (LVADs). The aim of this study was to identify if pre-LVAD right ventricular (RV) dysfunction is associated with risk of GIB after LVAD implantation. Of 398 patients implanted with LVADs between July 2008 and July 2016, 130 (33%) developed GIB at a median of 2.6 months following LVAD implantation. Arteriovenous malformations (AVMs) were found in 42 (34%) GIB patients. Patients with GIB were older and more likely to have hypertension, diabetes, and ischemic cardiomyopathy. On pre-LVAD echocardiography, GIB patients had increased RV diastolic dimension (4.7 ± 0.8 vs. 4.4 ± 0.9 cm, p = 0.02), a higher rate of greater than mild tricuspid valve (TV) regurgitation (73 [60%] vs. 120 [47%], p = 0.006), and underwent TV repair more often (38 [30%] vs. 43 [16%], p = 0.0006) during LVAD implantation. After multivariable adjustment, preoperative greater than mild RV enlargement (hazard ratio [HR] 2.32, 95% CI 1.12-5.03; p = 0.03), TV regurgitation (HR 1.83, CI 1.02-3.44; p = 0.01), and TV repair (HR 3.76, confidence interval [CI] 1.02-4.44; p = 0.01) remained associated with risk of GIB. This finding was driven by the AVM-GIB subgroup. Preoperative RV enlargement and TV regurgitation are associated with post-LVAD AVM-related GIB.

Prospective Multicenter Study of Myocardial Recovery Using Left Ventricular Assist Devices (RESTAGE-HF [Remission from Stage D Heart Failure]): Medium-Term and Primary End Point Results.

BACKGROUND: Left ventricular assist device (LVAD) unloading and hemodynamic support in patients with advanced chronic heart failure can result in significant improvement in cardiac function allowing LVAD removal; however, the rate of this is generally considered to be low. This prospective multicenter nonrandomized study (RESTAGE-HF [Remission from Stage D Heart Failure]) investigated whether a protocol of optimized LVAD mechanical unloading, combined with standardized specific pharmacological therapy to induce reverse remodeling and regular testing of underlying myocardial function, could produce a higher incidence of LVAD explantation. METHODS: Forty patients with chronic advanced heart failure from nonischemic cardiomyopathy receiving the Heartmate II LVAD were enrolled from 6 centers. LVAD speed was optimized with an aggressive pharmacological regimen, and regular echocardiograms were performed at reduced LVAD speed (6000 rpm, no net flow) to test underlying myocardial function. The primary end point was the proportion of patients with sufficient improvement of myocardial function to reach criteria for explantation within 18 months with sustained remission from heart failure (freedom from transplant/ventricular assist device/death) at 12 months. RESULTS: Before LVAD, age was 35.1±10.8 years, 67.5% were men, heart failure mean duration was 20.8±20.6 months, 95% required inotropic and 20% temporary mechanical support, left ventricular ejection fraction was 14.5±5.3%, end-diastolic diameter was 7.33±0.89 cm, end-systolic diameter was 6.74±0.88 cm, pulmonary artery saturations were 46.7±9.2%, and pulmonary capillary wedge pressure was 26.2±7.6 mm Hg. Four enrolled patients did not undergo the protocol because of medical complications unrelated to the study procedures. Overall, 40% of all enrolled (16/40) patients achieved the primary end point, P<0.0001, with 50% (18/36) of patients receiving the protocol being explanted within 18 months (pre-explant left ventricular ejection fraction, 57±8%; end-diastolic diameter, 4.81±0.58 cm; end-systolic diameter, 3.53±0.51 cm; pulmonary capillary wedge pressure, 8.1±3.1 mm Hg; pulmonary artery saturations 63.6±6.8% at 6000 rpm). Overall, 19 patients were explanted (19/36, 52.3% of those receiving the protocol). The 15 ongoing explanted patients are now 2.26±0.97 years after explant. After explantation survival free from LVAD or transplantation was 90% at 1-year and 77% at 2 and 3 years. CONCLUSIONS: In this multicenter prospective study, this strategy of LVAD support combined with a standardized pharmacological and cardiac function monitoring protocol resulted in a high rate of LVAD explantation and was feasible and reproducible with explants occurring in all 6 participating sites. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01774656.

Impact of temporary mechanical circulatory support for early graft failure on post-heart transplantation outcomes.

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.

Impaired Exercise Tolerance Early After Heart Transplantation Is Associated With Development of Cardiac Allograft Vasculopathy.

BACKGROUND: Exercise performance remains limited in some patients after heart transplantation (HTx). The goal of this study was to assess for association between cardiopulmonary exercise test performance at 1 year after HTx and future development of cardiac allograft vasculopathy (CAV). METHODS: Overall 243 HTx recipients performed cardiopulmonary exercise testing at 1 year after HTx. During the median follow-up period of 31 (interquartile range 19;61) months, 76 (32%) patients were diagnosed with CAV (CAV group). RESULTS: The CAV group patients had lower exercise capacity (5.2 ± 1.9 versus 6.5 ± 2.2 metabolic equivalents; P = 0.001) and duration (9.6 ± 3.5 versus 11.4 ± 4.8 min; P = 0.008), lower peak oxygen consumption (VO2) (18.4 ± 5.4 versus 21.4 ± 6.1 mL/kg/min; P = 0.0005), lower normalized peak VO2 (63% ± 18% versus 71% ± 19%; P = 0.007), and higher minute ventilation (VE)/carbon dioxide production (VCO2) (34 ± 5 versus 32 ± 5, P = 0.04). On Cox proportional hazards regression analysis, normalized peak VO2 ≤60%, and VE/VCO2 ≥34 were associated with a high hazard for CAV (HR = 1.8 [95% CI 1.10-4.53, P = 0.03] and 2.5 [95% CI 1.01-8.81, P = 0.04], respectively). The subgroup of patients with both normalized peak VO2 ≤60% and VE/VCO2 ≥34 was at highest risk for development of CAV (HR = 5.2, 95% CI 2.27-15.17, P = 0.001). CONCLUSIONS: Normalized peak VO2 ≤60% and VE/VCO2 ≥34 at 1 year after HTx are associated with the development of CAV.

Can we expect improvements in outcomes with centrifugal vs axial flow left ventricular assist devices in patients transitioned from extracorporeal life support?

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.

A Fully Magnetically Levitated Left Ventricular Assist Device - Final Report.

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.).

Elevated Heart Rate Following Heart Transplantation Is Associated With Increased Graft Vasculopathy and Mortality.

BACKGROUND: The effect of elevated heart rate (HR) on outcomes after heart transplantation (HT) has not been well established. The aim of this study was to assess predictors of elevated HR following HT and its impact on outcomes. METHODS AND RESULTS: We retrospectively evaluated 394 patients who underwent HT at 2 academic medical centers from 2005 to 2016. Patients were divided into 2 groups based on HR 1 year after HT: HR ≥95 beats/min (n = 162; 41%) and HR <95 beats/min (n = 232; 59%). Median follow-up time was 6.6 (interquartile range [IQR] 2.2-7.5) years. HR ≥95 beats/min 1 year after HT was associated with younger donor age, whereas HR <95 beats/min was associated with heavy donor alcohol use and African-American recipient race. Left ventricular (LV) end-diastolic dimension, mass, and ejection fraction were lower and E/E' higher in the HR ≥95 group at the time of the last follow up. HR ≥95 beats/min at 1 year after HT was independently associated with the development of cardiac allograft vasculopathy and increased mortality. CONCLUSIONS: HR ≥95 beats/min 1 year after HT is associated with a reduction in LV size and function, increased incidence of cardiac allograft vasculopathy, and reduced survival. Studies investigating the effect of medical HR reduction on post-HT outcomes are warranted.

Molecular discoveries and treatment strategies by direct reprogramming in cardiac regeneration.

Cardiac tissue has minimal endogenous regenerative capacity in response to injury. Treatment options are limited following tissue damage after events such as myocardial infarction. Current strategies are aimed primarily at injury prevention, but attention has been increasingly targeted toward the development of regenerative therapies. This review focuses on recent developments in the field of cardiac fibroblast reprogramming into induced cardiomyocytes. Early efforts to produce cardiac regeneration centered around induced pluripotent stem cells, but clinical translation has proved elusive. Currently, techniques are being developed to directly transdifferentiate cardiac fibroblasts into induced cardiomyocytes. Viral vector-driven expression of a combination of transcription factors including Gata4, Mef2c, and Tbx5 induced cardiomyocyte development in mice. Subsequent combinational modifications have extended these results to human cell lines and increased efficacy. The miRNAs including combinations of miR-1, miR-133, miR-208, and miR-499 can improve or independently drive regeneration of cardiomyocytes. Similar results could be obtained by combinations of small molecules with or without transcription factor or miRNA expression. The local tissue environment greatly impacts favorability for reprogramming. Modulation of signaling pathways, especially those mediated by VEGF and TGF-ß, enhance differentiation to cardiomyocytes. Current reprogramming strategies are not ready for clinical application, but recent breakthroughs promise regenerative cardiac therapies in the near future.

The effect of donor alcohol abuse on outcomes following heart transplantation.

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.