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We are entering 2021 with an expanding and effective COVID-19 vaccine armamentarium. Recent interim results from COVID-19 vaccine trials, including more than 80,000 participants worldwide, demonstrate remarkable efficacy and low rate of serious adverse events. Based on experience with other vaccines in transplant recipients and knowing the risk of severe COVID-19 in this population, we believe that COVID-19 vaccines provide potential benefit with minimal risk. We strongly support and encourage COVID-19 vaccination of our transplant recipients. [ABSTRACT FROM AUTHOR]

Background Primary outcomes analysis of the Multicenter Study of MagLev Technology in Patients Undergoing MCS Therapy With HeartMate 3 (MOMENTUM 3) trial short-term cohort demonstrated a higher survival rate free of debilitating stroke and reoperation to replace/remove the device (primary end-point) in patients receiving the HeartMate 3 (HM3) compared with the HeartMate (HMII). In this study we sought to evaluate the individual and interactive effects of pre-specified patient subgroups (age, sex, race, therapeutic intent [bridge to transplant/bridge to candidacy/destination therapy] and severity of illness) on primary end-point outcomes in MOMENTUM 3 patients implanted with HM3 and HMII devices. Methods Cox proportional hazard models were used to analyze patients enrolled in the “as-treated cohort” ( n = 289) of the MOMENTUM 3 trial to: (1) determine interaction of various subgroups on primary end-point outcomes; and (2) identify independent variables associated with primary end-point success. Results Baseline characteristics were well balanced among HM3 ( n = 151) and HMII ( n = 138) cohorts. No significant interaction between the sub-groups on primary end-point outcomes was observed. Cox multivariable modeling identified age (≤65 years vs >65 years, hazard ratio 0.42 [95% confidence interval 0.22 to 0.78], p = 0.006]) and pump type (HM3 vs HMII, hazard ratio 0.53 [95% confidence interval 0.30 to 0.96], p = 0.034) to be independent predictors of primary outcomes success. After adjusting for age, no significant impact of sex, race, therapeutic intent and INTERMACS profiles on primary outcomes were observed. Conclusions This analysis of MOMENTUM 3 suggests that younger age (≤65 years) at implant and pump choice are associated with a greater likelihood of primary end-point success. These findings further suggest that characterization of therapeutic intent into discrete bridge-to-transplant and destination therapy categories offers no clear clinical advantage, and should ideally be abandoned. [ABSTRACT FROM AUTHOR]

Pump thrombosis is a dreaded complication of long-term implantable ventricular assist devices. No guidance exists regarding the diagnosis and management of this entity despite its significant morbidity. After considerable thought and deliberation, a group of leading investigators in the field of mechanical support propose an algorithm for the diagnosis and management of this vexing entity based on clinical symptoms and serologic and imaging studies. [ABSTRACT FROM AUTHOR]

Background: Although continuous-flow left ventricular assist device (LVAD) support has become standard therapy, the complexities of device and patient management remain a challenge. In particular, percutaneous site infections (PSI) are a serious complication during the post-implant course. We sought to study the incidence, risk factors, and clinical effect of PSI. Methods: Data were obtained from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Registry. All adult patients who received a primary intracorporeal continuous flow LVAD between June 2006 and September 2010 were included. Descriptive statistics, Kaplan-Meier depictions, and multivariable analysis in the parametric hazard domain were used for statistical analysis. Results: A total of 239 PSIs were documented in 197 of 2,006 recipients (9.8%) of a continuous-flow LVAD. Mean follow-up was 8.1 months. Mean time to development of a PSI was 6.6 months. At 1 year after implant, nearly 19% of continuous-flow LVAD recipients developed a PSI. Multivariate analysis showed younger age (hazard ratio, 1.20; p < 0.0001) was the only factor predicting a PSI. Continuous-flow LVAD recipients who did not develop a PSI had improved survival (p = 0.004). Twenty-three patients died after development of a PSI. Sepsis was the most common cause of death (26.1%). Conclusions: PSIs occur in approximately 19% of continuous-flow LVAD recipients by 12 months after implant. Young age is the only predictor of PSI. Importantly, development of a PSI adversely affects survival. Efforts to enhance driveline integration and to develop future totally implantable systems are warranted. [ABSTRACT FROM AUTHOR]

Background: Cardiac transplantation in many centers is programmatically limited to patients aged younger than 70 years. We investigated the trends and outcomes for cardiac transplantation in recipients aged 70 years and older in the United States. Methods: De-identified data were provided by United Network of Organ Sharing. Transplant recipients were grouped by age 60–69 years and 70 years and older. Univariate comparisons were performed using Student''s t-test or the Pearson chi-square test. Survival was estimated using the Kaplan-Meier technique and compared with the log-rank test. Cox regression was used to determine predictors of death after transplant. Statistical significance was assigned to p < 0.05. Results: Between January 1, 1998, and June 15, 2010, 5,807 sexagenarians and 332 septuagenarians received allografts. The septuagenarian cohort had more men, less diabetes, was less likely to have a ventricular assist device, and more likely to be status II. Donors for septuagenarians were older and died more frequently from intracranial hemorrhage. Median unadjusted survival was 9.8 years for sexagenarians vs 8.5 years for septuagenarians (p = 0.003). There was no difference in the incidence of cerebrovascular accident, length of stay, or pacemaker need between groups. Septuagenarians were less likely to be treated for rejection the first year (p = 0.001). Age was a multivariate predictor of death (hazard ratio, 1.289; 95% confidence interval, 1.039–1.6; p = 0.021). Conclusions: Selected septuagenarians with advanced heart failure can derive great benefit from cardiac transplantation, although survival is inferior to that of an immediately younger sexagenarian cohort. Most of the mortality risk is seen in the first year after transplantation. A reduced incidence of rejection was observed and warrants further study. [Copyright &y& Elsevier]

Innate immunity represents the first line of defense against microbial invasion. Recent studies have determined that a group of germline-encoded receptors, termed Toll-like receptors (TLRs), are critical for recognizing foreign motifs on microbial organisms and initiating innate responses. An exciting area of research has recently linked activation of TLRs on antigen-presenting cells (APCs) to effective antigen presentation and activation of naive T cells. Most studies have shown that TLR-dependent immune function leads to T-helper 1 (TH1) immunity, although evidence also supports that TH2 immune responses may be initiated by TLR signaling in certain contexts. In either case, innate immune signaling via TLRs leads to a productive adaptive immune response. In contrast to studies in purely infectious models, emerging data from experimental and clinical studies have provided evidence that TLR immune function is important in acute allograft rejection. Specifically, MyD88, an important TLR signal adaptor, was found to be critical for the rejection of minor-mismatched skin allografts, and important for alloimmune priming and TH1 immunity against fully allogeneic skin grafts. Furthermore, a clinical study has shown that recipients with TLR 4 polymorphisms associated with endotoxin hyporesponsiveness manifest reduce acute lung allograft rejection. Collectively, these studies demonstrate that innate immunity is important for alloimmunity. Future therapeutic modalities that target innate rather than adaptive immune mechanisms represent a promising avenue for future studies in thoracic organ transplantation. [Copyright &y& Elsevier]

Left ventricular assist devices (LVADs) are excellent therapies for advanced heart failure patients either bridged to transplant or for lifetime use. LVADs also allow for reverse remodeling of the failing heart that is often associated with functional improvement. Indeed, growing enthusiasm exists to better understand this population of patients, whereby the LVAD is used as an adjunct to mediate myocardial recovery. When patients achieve benchmarks suggesting that they no longer need LVAD support, questions related to the discontinuation of LVAD therapy become front and center. The purpose of this review is to provide a surgical perspective on the practical and technical issues surrounding LVAD deactivation. [ABSTRACT FROM AUTHOR]

The HeartMate 3 left ventricular assist system (LVAS; St. Jude Medical, Inc., formerly Thoratec Corporation, Pleasanton, CA) was recently introduced into clinical trials for durable circulatory support in patients with medically refractory advanced-stage heart failure. This centrifugal, fully magnetically levitated, continuous-flow pump is engineered with the intent to enhance hemocompatibility and reduce shear stress on blood elements, while also possessing intrinsic pulsatility. Although bridge-to-transplant (BTT) and destination therapy (DT) are established dichotomous indications for durable left ventricular assist device (LVAD) support, clinical practice has challenged the appropriateness of these designations. The introduction of novel LVAD technology allows for the development of clinical trial designs to keep pace with current practices. The prospective, randomized Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) clinical trial aims to evaluate the safety and effectiveness of the HeartMate 3 LVAS by demonstrating non-inferiority to the HeartMate II LVAS (also St. Jude Medical, Inc.). The innovative trial design includes patients enrolled under a single inclusion and exclusion criteria , regardless of the intended use of the device, with outcomes ascertained in the short term (ST, at 6 months) and long term (LT, at 2 years). This adaptive trial design includes a pre-specified safety phase ( n = 30) analysis. The ST cohort includes the first 294 patients and the LT cohort includes the first 366 patients for evaluation of the composite primary end-point of survival to transplant, recovery or LVAD support free of debilitating stroke (modified Rankin score >3), or re-operation to replace the pump. As part of the adaptive design, an analysis by an independent statistician will determine whether sample size adjustment is required at pre-specified times during the study. A further 662 patients will be enrolled to reach a total of 1,028 patients for evaluation of the secondary end-point of pump replacement at 2 years. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate a novel virtual care platform created for use in Left Ventricular Assist Device (LVAD) patients. The platform included a daily log of LVAD parameters and medication adherence, two-way messaging with providers, and educational resources. To test the feasibility of this application, we recruited 25 patients between 2017 and 2019 and followed them for 6 months post discharge. Feedback concerning the platform was very positive with an average score of 4.5 ± 0.6 (out of 5) on usability and/or satisfaction and 8.1 ± 1.8 (out of 10) on likelihood to recommend the platform. In addition, our platform was well utilized with median (IQR) engagement rates of 87 (53,100)% at 30 days and 73 (49,95)% overall. We found that patients using the platform attended significantly less outpatient visits at the 6 month mark, however there was no difference in 30-day readmission rates compared to the overall LVAD cohort. [ABSTRACT FROM AUTHOR]

Angiodysplasias (AGD) are common sites of bleeding in the gastrointestinal (GI) tract after Continuous Flow Left Ventricular Assist Device (CF-LVAD) implantation. We sought to investigate whether AGDs are formed as a result of LVAD physiology or preexist as a consequence of heart failure. Thirty-six subjects with HF reduced EF (HFrEF) underwent video capsule endoscopy (VCE) to assess for the presence of AGD. Fifty-three subjects without HF who underwent VCE for a nonbleeding indication formed a control group. The prevalence of AGD was significantly higher in the HFrEF compared to the non-HF controls (50% vs 13%, p = 0.0002). This association persisted after controlling for age and comorbidities. Within the HFrEF cohort, higher Ang2, NT-proBNP and BUN were associated with the presence of AGD. AGD in the GI tract are associated with HFrEF. This is the first description of a new pathology associated with HFrEF and adds to our understanding of CF LVAD associated GI bleeding. [ABSTRACT FROM AUTHOR]

There is little insight into which patients can be weaned off right ventricular (RV) acute mechanical circulatory support (AMCS) after left ventricular assist device (LVAD) implantation. We hypothesize that concomitant RV AMCS insertion instead of postoperative implantation will improve 1-year survival and increase the likelihood of RV AMCS weaning. A multicenter retrospective database of 826 consecutive patients who received a HeartMate II or HVAD between January 2007 and December 2016 was analyzed. We identified 91 patients who had early RV AMCS on index admission. Cox proportional-hazards model was constructed to identify predictors of 1-year mortality post-RV AMCS implantation and competing risk modeling identified RV AMCS weaning predictors. There were 91 of 826 patients (11%) who required RV AMCS after CF-LVAD implantation with 51 (56%) receiving a concomitant RV AMCS and 40 (44%) implanted with a postoperative RV AMCS during their ICU stay; 48 (53%) patients were weaned from RV AMCS support. Concomitant RV AMCS with CF-LVAD insertion was associated with lower mortality (HR 0.45 [95% CI 0.26-0.80], p = 0.01) in multivariable model (which included age, BMI, angiotensin-converting enzyme inhibitor use, and heart transplantation as a time-varying covariate). In the multivariate competing risk analysis, a TPG < 12 (SHR 2.19 [95% CI 1.02-4.70], p = 0.04) and concomitant RV AMCS insertion (SHR 3.35 [95% CI 1.73-6.48], p < 0.001) were associated with a successful wean. In patients with RVF after LVAD implantation, concomitant RV AMCS insertion at the time of LVAD was associated with improved 1-year survival and increased chances of RV support weaning compared to postoperative insertion. [ABSTRACT FROM AUTHOR]

The trends and outcomes of multiorgan heart-transplantation (HT) using hepatitis C virus (HCV) donors in the contemporary era are sparsely known. Using UNOS registry, 1322 adult multiorgan-HTs (n = 986 heart-kidney, n = 155 heart-lung, n = 181 heart-liver) between August-2015 and August-2020 were identified, of which 109 were performed using HCV-donors (n = 77 HCV nucleic-acid-amplification testing [NAT] positive irrespective of antibody status [HCV-viremic]; and n = 32 HCV Ab+/NAT-[HCV antibody + nonviremic]). The percentage of HCV-donors used for multiorgan-HT increased from 0% in 2015 to 14% in 2020 (p < 0.001), but there was wide variation across UNOS regions and center volumes. Recipients of multiorgan heart-kidney transplants from HCV-donors (n = 90) and HCV-naïve (HCV Ab-/NAT-) donors (n = 896) had similar 1-year survival using unadjusted and adjusted Cox-proportional hazards-regression models including in propensity-score matched cohorts. Post-HT rates of cardiac-allograft-vasculopathy (5.4% vs 5.8%) and chronic-dialysis (7.3% vs 4.9%) at 1-year were also similar. Use of HCV-donors (HCV-viremic, HCV Ab+ nonviremic) for multiorgan-HT has increased significantly. Encouraging 1-year outcomes in heart-kidney recipients from HCV-donors should support further expansion of heart-kidney transplantation using HCV-donors. [ABSTRACT FROM AUTHOR]

Regional outcomes after implantation of continuous-flow left ventricular assist devices (LVADs) have not been described. We examined differences in patient selection, survival, and adverse events across 3 geographic regions of the world: the Americas, Asia-Pacific, and Europe. Using data from The International Society for Heart and Lung Transplantation Mechanically Assisted Circulatory Support registry, all adult patients implanted with a continuous-flow LVADs were included in this International Society for Heart and Lung Transplantation Mechanically Assisted Circulatory Support analysis (n = 15,560), of whom, 9,988 (64%) received axial-flow devices and 5,572 (36%) received centrifugal-flow devices. There were significant interregional differences in the rate of implantation of patients aged >70 years (Americas: 14%, Asia-Pacific: 1%, Europe: 5%; p < 0.0001), morbidly obese (Americas: 5%, Asia-Pacific: 1%, Europe: 1%; p < 0.0001), male (Americas: 79%, Asia-Pacific: 77%, Europe: 85%; p < 0.0001), and implanted as destination therapy (Americas: 48%, Asia-Pacific: 4%, Europe: 22%; p < 0.0001). The rates of centrifugal pump usage varied by region (Americas: 30%, Asia-Pacific: 34%, Eu: 74%; p < 0.0001). Survival rates varied by region and the type of pump flow, with survival at 12 and 48 months (axial flow vs centrifugal flow) being 82% vs 82% and 52% vs 53 in Americas; 92% vs 86% and 83% vs 74% in Asia-Pacific; and 80% vs 75% and 69% vs 53% in Europe, respectively (regional survival p < 0.0001). There are marked global differences in LVAD recipient characteristics, device utilization, and post-operative care. These heterogeneities along with differences in patient management and transplantation rates may impact long-term survival. Regional differences in adverse event incidence warrant further investigation. [ABSTRACT FROM AUTHOR]

In a randomized controlled trial (MOMENTUM 3), the HeartMate 3 (HM3) fully magnetically levitated centrifugal-flow left ventricular assist device (LVAD) demonstrated superiority over the HeartMate II (HMII) axial-flow LVAD. These findings were driven by hemocompatibility-related outcomes, but infection-related outcomes were not altered by device choice. In this trial-level analysis, we analyzed the clinical patterns of infection-related outcomes over 2 years of support. In MOMENTUM 3, 1,020 patients were implanted with either the HM3 (n = 515) or HMII (n = 505) pump. Clinical characteristics and morbidity- and mortality-related outcomes were evaluated to identify predictors associated with major infectious complications, using univariable and multivariable models. The cumulative number of infections at 2 years was 1,213 (634 HM3 and 579 HMII), and major infection occurred in 58% of patients with the HM3 and 56% of patients with the HMII (p = 0.57). Infections of a local nature unrelated to pump components were most common (n = 681/1,213; 56%), followed by driveline-associated infection (n = 329/1,213; 27%), sepsis (n = 194/1,213; 16%), and other events (n = 9/1,213; 0.7%). Bacterial pathogens were implicated in 806 of 1,213 events (66%); significant predictors of infection included sex (women vs men; hazard ratio [HR]: 1.38, p = 0.003), pre-implant use of intra-aortic balloon pump (HR: 1.33, p = 0.02), pre-implant history of cardiac surgery (HR: 1.28, p = 0.01), and body mass index ≥ 30 (HR: 1.40, p < 0.0001). Most deaths in those with infection occurred owing to non-infectious causes. Infection is the most common adverse effect in patients implanted with contemporary continuous-flow LVADs, with most such events unrelated to the pump or its peripheral components. Whether chronic mechanical circulatory devices confer an immunomodulatory effect pre-disposing to infection warrants closer scrutiny to understand and ameliorate this morbidity. [ABSTRACT FROM AUTHOR]

There is a lack of evidence to guide appropriate donor sizing in recipients with moderate pulmonary hypertension (pHTN) awaiting heart transplantation (HTx). It is common practice to oversize donor hearts for such recipients to prevent post-operative right ventricular failure. Therefore, our objective was to determine if oversizing in pre-transplant moderate pHTN provides a survival advantage. The United Network for Organ Sharing database was analyzed to include HTx recipients from 1994 to 2016. Recipients were considered as having moderate pHTN if the pulmonary vascular resistance (PVR) was 2.5 to 5 Wood units (WU) or transpulmonary gradient (TPG) was 10 to 18 mm Hg. Heart size mismatch was determined using the predicted heart mass equations. A size mismatch of ≥15% in either direction was considered undersized or oversized, respectively. Ninety-day and 1-year survival were analyzed based on size matching via univariate and Cox regression analysis. Propensity matching was performed to specifically evaluate the effect of donor sex among male transplant recipients. Among 29,441 HTx recipients, 10,666 had moderate pHTN by PVR criteria and 12,624 HTx patients had moderate pHTN according to TPG criteria. Among patients with a PVR of 2.5 to 5 WU, oversizing was not associated with lower mortality compared with matched hearts at 90 days (7.6% vs 7.4%; p = 0.75) and 1 year (12.1% vs 11.3%; p = 0.26). Conversely, undersizing the donor was associated with a higher 90-day (10.6% vs 7.6% vs 7.4%; p < 0.01) and 1-year (15.3% vs 12.1% vs 11.3%; p < 0.01) mortality than recipients receiving oversized or matched hearts, respectively. On Cox regression analysis, there was no benefit with oversizing at 90 days (hazard ratio [HR] 0.88; p = 0.23) and 1 year (HR 0.99; p = 0.90), whereas undersizing was associated with higher 90-day (HR 1.32; p = 0.02) and 1-year mortality (HR 1.23; p = 0.03) compared to size-matched controls. Among patients with moderate pHTN based on TPG of 10 to 18 mm Hg, neither undersizing nor oversizing was predictive of mortality at 90 days and 1 year according to Cox regression analysis. Propensity matching revealed that female-to-male transplantation had similar 1-year mortality to male-to-male transplantation, and there was no advantage to oversizing female donors for male recipients. In this registry-based analysis, there was no benefit to oversizing donors for cardiac transplant recipients with moderate pHTN. Elimination of this restriction could increase the donor pool and reduce wait times for such recipients. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Mitral regurgitation (MR) determines pathophysiology and outcome in advanced heart failure. The impact of left ventricular assist device (LVAD) placement on clinically significant MR and its contribution to long-term outcomes has been sparsely evaluated. We evaluated the effect of clinically significant MR on patients implanted in the MOMENTUM 3 trial with either the HeartMate II (HMII) or the HeartMate 3 (HM3) at 2 years. Clinical significance was defined as moderate or severe grade MR determined by site-based echocardiograms. Of 927 patients with LVAD implants without a prior or concomitant mitral valve procedure, 403 (43.5%) had clinically significant MR at baseline. At 1-month of support, residual MR was present in 6.2% of patients with HM3 and 14.3% of patients with HMII (relative risk = 0.43; 95% CI, 0.22–0.84; p = 0.01) with a low rate of worsening at 2 years. Residual MR at 1-month post-implant did not impact 2-year mortality for either the HM3 (hazard ratio [HR],1.41; 95% CI, 0.52–3.89; p = 0.50) or HMII (HR, 0.91; 95% CI, 0.37–2.26; p = 0.84) LVAD. The presence or absence of baseline MR did not influence mortality (HM3 HR, 0.86; 95% CI, 0.56–1.33; p = 0.50; HMII HR, 0.81; 95% CI, 0.54–1.22; p = 0.32), major adverse events or functional capacity. In multivariate analysis, severe baseline MR (p = 0.001), larger left ventricular dimension (p = 0.002), and implantation with the HMII instead of the HM3 LVAD (p = 0.05) were independently associated with an increased likelihood of persistent MR post-implant. Hemodynamic unloading after LVAD implantation improves clinically significant MR early, sustainably, and to a greater extent with the HM3 LVAD. Neither baseline nor residual MR influence outcomes after LVAD implantation. [ABSTRACT FROM AUTHOR]

Aspirin (ASA) anti-platelet therapy is mandated with left ventricular assist devices (LVADs) to prevent hemocompatibility-related adverse events (HRAEs). However, the optimal dose of ASA with HeartMate 3 (HM3) LVAD is unknown. In an exploratory analysis of HM3-supported patients in the MOMENTUM 3 study (NCT02224755), 2 groups were analyzed: usual-dose (325 mg) and low-dose (81 mg) ASA with anti-coagulation targeted to an international normalized ratio of 2.0 to 3.0. Exclusion criteria included patients not receiving either ASA 81 mg or 325 mg, those with HRAEs ≤7 days after device implantation, and those receiving >1 anti-platelet agent. The primary end-point was survival free from HRAEs (non-surgical bleeding, pump thrombosis, stroke, and peripheral arterial thromboembolic events) at 2 years. Overall, 321 HM3 patients (usual-dose: n = 141, low-dose: n = 180) were included in this analysis. Usual-dose group patients were younger (57 ± 13 vs 60 ± 12 years, p = 0.035) and less often assigned destination therapy (55% vs 67%, p = 0.029) than low-dose ASA. At 2 years, a similar proportion of patients in the usual- and low-dose groups (43.4% vs 45.3%, p = 0.94) met the primary end-point. There were no differences in survival free from hemorrhagic (usual-dose: 54.4% vs low-dose: 51.7%, p = 0.42) or thrombotic (usual-dose: 76.8% vs low-dose: 75.7%, p = 0.92) events. Usual- and low-dose ASA revealed similar rates of bleeding and thrombotic events in HM3 LVAD-supported patients within the MOMENTUM 3 trial. Whether ASA therapy provides any meaningful therapeutic effect in patients treated by the HM3 LVAD remains to be determined. [ABSTRACT FROM AUTHOR]

Patients with cardiogenic shock (CS) needing temporary circulatory support (TCS) have poor survival rates after implantation of durable ventricular assist device (dVAD). We aimed to characterize post-dVAD adverse event burden and survival rates in patients requiring pre-operative TCS. We analyzed 13,511 adults (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] Profiles 1–3) with continuous-flow dVADs in International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support (2013–2017) according to the need for pre-operative TCS (n = 5,632) vs no TCS (n = 7,879). Of these, 726 (5.4%) had biventricular assist devices (BiVAD). Furthermore, we compared prevalent rates (events/100 patient-months) of bleeding, device-related infection, hemorrhagic and ischemic cerebrovascular accidents (hemorrhagic cerebral vascular accident [hCVA], and ischemic cerebral vascular accident [iCVA]) in early (<3 months) and late (≥3 months) post-operative periods. TCS included extracorporeal membrane oxygenation (ECMO) (n = 1,138), intra-aortic balloon pump (IABP) (n = 3,901), and other TCS (n = 593). Within 3 post-operative months, there were more major bleeding and cerebrovascular accidents (CVAs) in patients with pre-operative ECMO (events/100 patient-months rates: bleeding = 19, hCVA = 1.6, iCVA = 2.8) or IABP (bleeding = 17.3, hCVA = 1.5, iCVA = 1.5) vs no TCS (bleeding = 13.2, hCVA = 1.1, iCVA = 1.2, all p < 0.05). After 3 months, adverse events were lower and similar in all groups. Patients with ECMO had the worst short- and long-term survival rates. Patients with BiVAD had the worst survival rate regardless of need for pre-operative TCS. CVA and multiorgan failures were the common causes of death for patients with TCS and patients without TCS. Patients requiring TCS before dVAD had a sicker phenotype and higher rates of early post-operative adverse events than patients without TCS. ECMO was associated with very high early ischemic stroke, bleeding, and mortality. The extreme CS phenotype needing ECMO warrants a higher-level profile status, such as INTERMACS "0." [ABSTRACT FROM AUTHOR]

Patients with advanced heart failure and cardiogenic shock (CS) often require temporary circulatory support (TCS) as a bridge to durable ventricular assist devices (dVADs). We aim to characterize longitudinal outcomes of patients with and without CS. Between 2013 and 2017, 13,813 adult patients classified as Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profiles 1 to 3 with continuous flow left ventricular assist devices or biventricular assist devices were registered into the International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support. Patients were sub-grouped according to support type (extracorporeal membrane oxygenation [ECMO], intra-aortic balloon pump [IABP], and other TCS). Other TCS included all other surgical and percutaneous TCS devices. Estimated survival was compared based on need for pre-operative TCS and by profile. Pre-operative TCS was used in 5,632 (41%) cases. Of these, ECMO was used in 1,138 (20%) cases, IABP in 3,901 (69%) cases, and other TCS in 595 (11%) cases. Patients requiring ECMO had greater needs for biventricular support after dVAD (22% ECMO, 5% IABP, and 7% other TCS; p < 0.001) with longer post-implant intensive care stays (ECMO 24 days, IABP 14 days, and other TCS 12 days; p < 0.001). INTERMACS Profile 1 to 3 patients with pre-implant ECMO had the lowest longitudinal survival (82% at 1 month and 44% at 48 months) compared with IABP (93% at 1 month and 51% at 48 months), other TCS (92% at 1 month and 52% at 48 months), and non-TCS (95% at 1 months and 55 % at 48 months) (p < 0.0001). Propensity score matching analysis of the pre-implant ECMO INTERMACS Profile 1 group when compared with alternative pre-implant TCS strategies had an associated higher hazard impacting early phase survival vs other TCS (hazard ratio, 1.80; p < 0.01) and IABP (hazard ratio, 1.65; p < 0.01). In advanced heart failure with patients with CS, the use of ECMO before dVAD was associated with lower longitudinal survival and increased utilization of biventricular support compared with alternative TCS strategies. Research focused on longitudinal profiling in CS and pre-implant TCS is warranted to further understand these differences. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) donors should be categorized as HCV-viremic (antibody [Ab] negative or positive/Nucleic Acid testing [NAT] positive) or HCV Ab + nonviremic (Ab+/NAT –). Whereas recipients of hearts from HCV-viremic donors will develop viremia but can be cured of HCV shortly after transplant with direct-acting antivirals (DAAs), recipients of hearts from HCV Ab+ nonviremic donors are highly unlikely to become viremic or require DAAs. Given this important difference in risk, we assessed the utilization trends and post-heart-transplantation outcomes of HCV-naive (Ab–/NAT–), HCV-viremic , and HCV Ab+ nonviremic donor hearts. A total of 26,572 adult donors (≥18 years) with information on HCV Ab and NAT status were identified in the United Network for Organ Sharing registry between August 2015 and June 2018 for utilization rates. Adult heart transplant recipients of these donors were compared for primary graft failure (PGF) at 90 days and 1-year recipient survival. A total of 96 HCV Ab+ nonviremic and 135 HCV-viremic adult donor hearts were transplanted during the study period. The utilization rates of both HCV Ab+ nonviremic (1.4% – 23.4%) and HCV-viremic (0.7% – 25.4%) donor hearts increased significantly approaching HCV-naive rates (29.04%). There was no significant difference in rates of PGF and 1-year survival between recipients in the 3 donor HCV groups. We also used (1:3) propensity score matching and found similar 1-year survival in different donor HCV groups (HCV-naive vs HCV Ab+ nonviremic, p = 0.59, and HCV-naive vs HCV-viremic, p = 0.98). Recipients of HCV-viremic and HCV Ab+ nonviremic donor hearts had equivalent risk of PGF and 1-year mortality compared with recipients of HCV-naive donor hearts. Although only HCV-viremic organs require DAAs and the risk of coronary artery vasculopathy after treated HCV infection has not been defined, the utilization rates of both HCV Ab+ nonviremic and HCV-viremic adult donor hearts have increased at an equal pace now approaching HCV-naive rates. [ABSTRACT FROM AUTHOR]

Increased shear stress conferred upon the circulation by continuous-flow pumps is associated with hemocompatibility-related adverse events, principally bleeding within the gastrointestinal system, and linked to the degradation of high-molecular-weight multimers (HMWMs) of von Willebrand factor (vWF). We evaluated the structure and functional characteristics of vWF HMWMs in patients with the fully magnetically levitated centrifugal-flow HeartMate 3 (HM3) and the continuous axial-flow HeartMate II (HMII) pump. Findings were correlated with bleeding events. In a prospective, multicenter, comparative cohort study, 60 patients from the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 Continued Access Protocol (NCT02892955) with an HM3 pump were compared with 30 randomly selected HMII patients from the PREVENtion of HeartMate II Pump Thrombosis study (NCT02158403) biobank. The primary end point was the difference in the normalized vWF HMWM ratio (ratio of the HMWMs to the intermediate- and low-molecular-weight multimers, normalized to pooled plasma from healthy volunteers) between the HM3 and the HMII pump at 90 days after implantation. Assay tests for vWF activity, vWF antigen, vWF activity to antigen ratio, coagulation factor VIII activity, and ADAMTS13 activity were measured by using standard protocols. Differences in these markers were compared in the context of clinical characteristics and correlated with adjudicated bleeding events within the HM3 group. Of 51 and 29 evaluable patients in the HM3 and HMII arms, respectively, those implanted with the HM3 pump exhibited greater preservation of the vWF HMWM ratio than those with the HMII pump at 90 days after implantation (54.1% vs 42.4%, p < 0.0001). Laboratory values for all vWF assays (antigen, activity, and coagulation factor VIII activity) remained within the normal functional range with no significant differences observed between the pumps at 90 days after implantation. At baseline, there was a decrease in the structural integrity of vWF HMWMs that correlated with increasing heart failure severity as measured by the Interagency Registry for Mechanically Assisted Circulatory Support profile. Multivariable modeling identified the HM3 pump as the only independent variable that determined post-implantation preservation of the structural integrity of vWF HMWMs. This prospective, multicenter comparative analysis study demonstrates that the fully magnetically levitated centrifugal-flow HM3 left ventricular assist device is associated with greater preservation of the structure of vWF HMWMs than the HMII mechanical bearing axial-flow pump. [ABSTRACT FROM AUTHOR]

BACKGROUND Hepatitis C (HCV) donors are rarely used for cardiac transplantation due to historically poor outcomes. In 2015, nucleic acid testing (NAT) for viral load was added to the routine work-up of organ donors, allowing for the distinction between subjects who remain viremic (HCV Ab+/NAT+) and those who have cleared HCV and are no longer viremic (HCV Ab+/NAT–). The American Society of Transplantation recently recommended that HCV Ab+/NAT– donors be considered non-infectious and safe for transplantation. We present our initial experience with such donors. METHODS All patients were counseled regarding donor HCV antibody (Ab) and NAT. Transplant recipients were tested post-transplant at 1 week and at 1, 3, and 6 months for HCV seropositivity and viremia. We also analyzed the UNOS database to determine the potential impact of widespread acceptance of HCV Ab+/NAT– organs. RESULTS Fourteen HCV Ab‒ subjects received hearts from HCV Ab+/NAT– donors in 2017. Over a median follow-up of 256 (192 to 377) days, 3 patients developed a reactive HCV Ab, yet none had a detectable HCV viral load during prospective monitoring at any time. Analysis of the UNOS database for the calendar year 2016 revealed that only 7 (3%) of 220 HCV Ab+/NAT– donors were accepted for heart transplantation. CONCLUSIONS We have demonstrated the feasibility of utilizing HCV Ab+/NAT– donors for cardiac transplantation without recipient infection. A small percentage of recipients developed HCV Ab without evidence of viremia, possibly consistent with a biological false reactive test, as has been seen in other settings. Large-scale validation of our data may have a significant impact on transplantation rates. [ABSTRACT FROM AUTHOR]

BACKGROUND Limited data exist describing impact of body mass index (BMI) on post‒left ventricular assist device (post-LVAD) outcomes. We sought to define the relationship between body mass index (BMI) and adverse events (AEs) after LVAD implantation by examining the ISHLT Mechanically Assisted Circulatory Support (IMACS) registry. METHODS Patients implanted with a contemporary continuous flow (CF)-LVAD were stratified into 4 groups using pre-operative BMI: underweight (UW; BMI ≤18.5 kg/m2); non-obese (NO; BMI >18.5 to <30 kg/m2); obese (OB; BMI ≥30 to <40 kg/m2); and morbidly obese (MO; BMI ≥40 kg/m2). Freedom from AEs was evaluated using the Kaplan–Meier method and risk factors for development of first AE were identified using multiphase parametric hazard modeling. AEs included infection, thromboembolic events, bleeding, device malfunction, and neurologic dysfunction. RESULTS Between 2013 and 2015, a total of 9,408 patients underwent implantation of a CF-LVAD, which consisted of 368 (4%) UW, 5,719 (61%) NO, 2,770 (29%) OB, and 444 (5%) MO patients. Survival among the 4 BMI cohorts was similar at 2 years (70.8% to 75.8%, p = 0.24). MO patients were less likely to be free from a non‒VAD-related infection (p < 0.0001) or device-related infection (p = 0.0014) at 2 years (50.3%, 70.7%) when compared with OB (58.3%, 78.7%), NO (65.2%, 81.4%), and UW (68.9%, 77.4%) patients. UW (81.5%) and NO (81.3%) patients were more likely to be free from device malfunction at 2 years when compared with OB (78.3%) and MO (72.6%) (p = 0.0006). Thromboembolic events were rare and more common in the UW cohort (p = 0.026). CONCLUSIONS Although BMI was not correlated with 2-year mortality, an increased rate of infectious and device-related AEs was noted in OB and MO LVAD patients. In a group with few options for transplant, the event morbidity in obese patients can be expected to impact morbidity with longer support durations. [ABSTRACT FROM AUTHOR]

Background We used multicenter international data from the International Society of Heart and Lung Transplantation Mechanically Assisted Circulation Support (IMACS) registry to determine bloodstream infection (BSI) event rate, independent risk factors, and association with mortality. Methods Included were patients registered in IMACS from January 2013 through December 2015, assessed BSI event rate of mechanical circulatory support (MCS) and non–MCS-related BSIs, and conducted univariate and multivariate analyses between BSI with baseline characteristics and mortality. Results We documented 1,606 BSIs in 1,231 of 10,171 MCS recipients (12%), with an event rate of 2.43 BSIs/100 patient-months within 3 months after implant (early onset) and 1.03 BSIs/100 patient-months after 3 months (late onset). Of these episodes, 1,378 (85.8%) were non– MCS-related BSI. Increasing body mass index and bilirubin were independent correlates of MCS-related BSI. Independent correlates of non–MCS-related BSI included older age, higher body mass index, previous cardiac surgery, baseline chronic renal disease and dialysis, pre-implant frailty, presence of biventricular assist device, total artificial heart or right ventricular assist device, and Interagency Registry for Mechanically Assisted Circulatory Support category 1. Survival after 3 months after implant of patients who developed early-onset BSI was 56.9% at 24 months vs 77.4% in patients without early-onset BSI ( p < 0.001). Early-onset BSI was an independent correlate of mortality at 3 months after implantation (hazard ratio, 2.56; 95% confidence interval, 2.09-3.15; p < 0.001). Conclusions Early-onset BSI was associated with significantly increased 24-month mortality. More than 85% of these BSIs were not device related. There is an opportunity for infection prevention practices to decrease the BSI event rate, which may affect 24-month survival. These data can also serve as benchmarking for individual institutions. [ABSTRACT FROM AUTHOR]

The second annual IMACS registry report includes over 14, 000 patients from 35 countries. Survival, adverse events, and an updated risk model is presented. Continuous flow pumps continue to dominate the world’s experience. One and Two-year survival remains at 80% and 70%. Congenital heart disease and biventricular support are the most dominant risk factors. The database is poised for major novel analyses. [ABSTRACT FROM AUTHOR]

The National Institutes of Health National Heart, Lung, and Blood Institute convened a working group in March 2008 to discuss how therapies for heart failure (HF) might be best advanced using clinical trials involving left ventricular assist devices (LVAD). This group opined that the field was ready for a trial to assess the use of long-term ventricular assist device therapy in patients who are less ill than patients currently eligible for destination therapy, which resulted in the R andomized E valuation of V AD I nter VE ntion before I notropic T herapy (REVIVE-IT) pilot study. The specific objective of REVIVE-IT was to compare LVAD therapy with optimal medical management in patients with less advanced HF than current LVAD indications to determine if wider application of permanent LVAD use to less ill patients would be associated with improved survival, quality of life, or functional capacity. REVIVE-IT represented an extraordinary effort to provide data from a randomized clinical trial to inform clinicians, scientists, industry, and regulatory agencies about the efficacy and safety of LVAD therapy in a population with less advanced HF. Despite significant support from the medical community, industry, and governmental agencies, REVIVE-IT failed to accomplish its goal. The reasons for its failure are instructive, and the lessons learned from the REVIVE-IT experience are likely to be relevant to any future study of LVAD therapy in a population with less advanced HF. [ABSTRACT FROM AUTHOR]

Background Atrial fibrillation (AF) is a well-established risk factor for thromboembolic (TE) complications. AF is frequently found in patients with advanced heart failure, including patients undergoing left ventricular assist device (LVAD) implantation. However, reports on whether preoperative AF increases the risk of TE events after LVAD implantation are scarce and limited to single-center or 2-center studies. We sought to evaluate the association of preoperative AF with TE events and patient survival using the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). Methods A retrospective analysis of INTERMACS data of primary continuous-flow LVADs implanted between May 2012 and December 2013 was performed. Adult patients were dichotomized as having AF or no AF (NAF). TE events were defined as cerebrovascular accident, transient ischemic attack, hemolysis, arterial non–central nervous system embolism, or explant because of pump thrombosis. Kaplan-Meier analysis and multivariate Cox regression were performed for freedom from TE and patient survival. Results Of 3,909 patients identified during the study period, 838 (21.4%) had preoperative AF. Patients with AF were older, were likely to be male, and had more comorbidities ( p < 0.01). In the AF group, 236 TE events occurred in 175 (20.9%) patients. In the NAF group, 900 TE events occurred in 691 (22.5%) patients. The TE event rate was not significantly different between the 2 groups (0.36 events/patient-year in AF group vs 0.37 events/patient-year in NAF group, p = 0.60). On univariate analysis, AF was not significantly associated with freedom from TE but was associated with decreased patient survival (log-rank test p = 0.03). On multivariate analysis, AF was not significantly associated with either TE (adjusted hazard ratio 0.95; 95% confidence interval, 0.80–1.13) or patient survival (adjusted hazard ratio 1.09; 95% confidence interval, 0.91–1.31). Conclusions Analysis of INTERMACS suggests that preoperative AF may not increase the risk of postoperative TE complications or patient mortality on midterm follow-up. Longer follow-up to confirm these findings is warranted. [ABSTRACT FROM AUTHOR]

Background: Pump thrombosis remains an uncommon but potentially catastrophic complication of durable continuous-flow left ventricular assist devices (LVAD). A perceived increase in the incidence of pump thrombosis in the HeartMate II (HMII) LVAD (Thoratec, Pleasanton, CA) by clinicians prompted this analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database. Methods: Between 2006 and June 2013, 8,988 United States patients aged older than 18 years received a durable LVAD. Of these, 6,910 adult patients from 132 institutions who received a HMII LVAD were entered in the INTERMACS database and constitute the study group for this analysis. Results: Overall survival (with censoring at transplant or explant for recovery) with the HMII LVAD was 80% at 1 year and 69% at 2 years and was not significantly different when stratified by era of implant. Freedom from device exchange or death due to thrombosis decreased from 99% at 6 months in 2009 to 94% in 2012 (p < 0.0001). Multivariable hazard function analysis showed risk factors for pump thrombosis included later implant year (p < 0.0001), younger age (p < 0.0001), higher creatinine (p = 0.002), larger body mass index (p = 0.004), white race (p = 0.0004), left ventricular ejection fraction above 20% (p = 0.02), and higher lactate dehydrogenase level at 1 month (p < 0.0001). Survival (p < 0.0001) and freedom from infection (p = 0.008) and cerebrovascular accident (p < 0.0001) were lower after pump exchange than after primary implant. Conclusions: Pump exchange or death due to pump thrombosis increased during 2011 and 2012, but the magnitude of the increase remained relatively small. Survival remains high (80% at 1 year) with the HMII LVAD. Risk factor analysis suggests that a number of patient-related factors contribute to the risk of thrombosis. Markedly elevated lactate dehydrogenase in the first month is a predictor of pump thrombosis. This analysis could not examine the potential role of technical factors during implant, such as sub-optimal pump or graft positioning, changes in patient management paradigms with pump speed settings, improved recognition and change in the threshold for pump exchange, or design or production changes with the pump, as contributors to the risk of pump thrombosis. [Copyright &y& Elsevier]

Background: Combining mechanical unloading by a continuous-flow left ventricular assist device (CF-LVAD) and neurohormonal blockade with heart failure medications (HFMED) is an underexplored clinical strategy to promote recovery of cardiac function in patients with advanced heart failure (HF). Methods: We implemented a clinical protocol to achieve maximal neurohormonal blockade after placement of a CF-LVAD and assessed its utility in an LVAD weaning (6,200 rpm) study. Thirty-four subjects were enrolled after CF-LVAD and were managed with aggressive, bi-weekly up-titration of HFMED. Results: Twenty-one subjects (8 with coronary artery disease, 13 with idiopathic dilated cardiomyopathy) were included in this LVAD weaning investigation. Overall, combined CF-LVAD and HFMED resulted in significant reverse remodeling with a decrease in left atrial volume index (44.7±16.0 to 31.6±12.1 ml/m2, p < 0.001) and LV internal diastolic diameter (6.7±1.5 to 6.0±1.6 cm, p = 0.003) and an increase in LV ejection fraction (17.4±6.5 to 33.1±16.2%, p < 0.001) during LVAD weaning (6,200 rpm). Five of 21 (24%) subjects demonstrated recovery of biventricular function. Exploratory analysis showed that recovered subjects had shorter duration HF, less myocardial fibrosis and less myocyte hypertrophy, and were supported at higher LVAD speeds. Conclusions: CF-LVAD support in combination with HFMED leads to significant reverse remodeling in patients with advanced HF. Using this approach, one quarter of patients demonstrated complete recovery of cardiac function. Our results suggest that bridge to recovery in the current device era is a clinically meaningful phenomenon and merits further investigation. [ABSTRACT FROM AUTHOR]

Institutional Affiliations: Co-chairs: Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, Georgia Institute of Technology and Morehouse School of Medicine; Pamboukian SV: University of Alabama at Birmingham, Birmingham, Alabama; Teuteberg JJ: University of Pittsburgh, Pittsburgh, Pennsylvania Task force chairs: Birks E: University of Louisville, Louisville, Kentucky; Lietz K: Loyola University, Chicago, Maywood, Illinois; Moore SA: Massachusetts General Hospital, Boston, Massachusetts; Morgan JA: Henry Ford Hospital, Detroit, Michigan Contributing writers: Arabia F: Mayo Clinic Arizona, Phoenix, Arizona; Bauman ME: University of Alberta, Alberta, Canada; Buchholz HW: University of Alberta, Stollery Children’s Hospital and Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada; Deng M: University of California at Los Angeles, Los Angeles, California; Dickstein ML: Columbia University, New York, New York; El-Banayosy A: Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; Elliot T: Inova Fairfax, Falls Church, Virginia; Goldstein DJ: Montefiore Medical Center, New York, New York; Grady KL: Northwestern University, Chicago, Illinois; Jones K: Alfred Hospital, Melbourne, Australia; Hryniewicz K: Minneapolis Heart Institute, Minneapolis, Minnesota; John R: University of Minnesota, Minneapolis, Minnesota; Kaan A: St. Paul’s Hospital, Vancouver, British Columbia, Canada; Kusne S: Mayo Clinic Arizona, Phoenix, Arizona; Loebe M: Methodist Hospital, Houston, Texas; Massicotte P: University of Alberta, Stollery Children’s Hospital, Edmonton, Alberta, Canada; Moazami N: Minneapolis Heart Institute, Minneapolis, Minnesota; Mohacsi P: University Hospital, Bern, Switzerland; Mooney M: Sentara Norfolk, Virginia Beach, Virginia; Nelson T: Mayo Clinic Arizona, Phoenix, Arizona; Pagani F: University of Michigan, Ann Arbor, Michigan; Perry W: Integris Baptist Health Care, Oklahoma City, Oklahoma; Potapov EV: Deutsches Herzzentrum Berlin, Berlin, Germany; Rame JE: University of Pennsylvania, Philadelphia, Pennsylvania; Russell SD: Johns Hopkins, Baltimore, Maryland; Sorensen EN: University of Maryland, Baltimore, Maryland; Sun B: Minneapolis Heart Institute, Minneapolis, Minnesota; Strueber M: Hannover Medical School, Hanover, Germany Independent reviewers: Mangi AA: Yale University School of Medicine, New Haven, Connecticut; Petty MG: University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota; Rogers J: Duke University Medical Center, Durham, North Carolina [Copyright &y& Elsevier]

Background: Prior retrospective studies have suggested that tacrolimus monotherapy is an option associated with excellent outcomes and reduced toxicities. Method: We conducted a prospective, randomized, 2-center study of tacrolimus combination therapy vs monotherapy. From April 16, 2004, to September 15, 2005, 58 adult heart transplant patients were studied. All received oral tacrolimus, mycophenolate mofetil, and corticosteroids. Patients were then randomized to a group where mycophenolate was maintained (COMBO) or to a group where it was discontinued (MONO) 14 days post-transplant. Corticosteroids were rapidly withdrawn in both groups between 8 and 12 weeks. Result: The primary end point (mean 6-month International Society of Heart and Lung Transplantation biopsy score) was 0.44 ± 0.04 in the MONO group and 0.60 ± 0.05 in the COMBO group (p = 0.013, unpaired Student’s t-test). The freedom from rejection grade of 2R or higher at 6 and 12 months was 93.3% with MONO and 92.9% with COMBO (p = NS). Conclusion: Tacrolimus monotherapy appears to be safe and efficacious in heart transplant recipients and is not associated with excess rejection in the first year post-transplant. Further studies of this approach are warranted. [Copyright &y& Elsevier]

Background: Ventricular assist devices (VADs) are increasingly used to support critically ill heart failure patients awaiting transplantation. Previous work has focused on the Thoratec Heartmate VE device, use of which is associated with pre-formed antibody production. We reviewed our cumulative experience with the Worldheart Novacor VAD as a bridge to transplantation (BTT). Methods: From January 1989 through October 2002, 39 patients required a VAD bridge, with 26 of 39 surviving to transplantation. Antibody levels were assessed by complement-dependent cytotoxicity assay at routine intervals and expressed as panel reactive antibody (PRA) levels. Post-transplant allograft rejection, coronary vasculopathy, and survival were compared between Novacor-supported patients and non-VAD transplant recipients. Results: PRA values did not significantly change after VAD implantation (12.4% ± 11.2% vs 14.8% ± 12.3%, p = 0.28). Survival for the BTT patients was 80.4%, 75.7%, 64.0%, 64.0%, and 64.0%, respectively, for 1, 3, 5, 7, and 10 years post-transplant, with similar results for non-BTT patients. The freedom from coronary vasculopathy was 90.2%, 90.2%, 72.2%, and 72.2%, respectively, at 1, 3, 5, and 7 years post-transplant. Conclusions: First, to our knowledge, this study is the first to examine the incidence of allosensitization after Novacor implant in detail. In contrast with previous results of work with other VAD systems, as assessed by PRA levels, Novacor patients did not become sensitized. Second, compared with 220 non-BTT patients who received transplants during a similar time frame, Novacor BTT patients had equivalent rejection profiles and survival. Finally, the incidence of transplant-associated coronary artery disease was lower than in previous reports. [Copyright &y& Elsevier]