M. Wigger

Benefits of ambulatory axillary intra-aortic balloon pump for circulatory support as bridge to heart transplant.

OBJECTIVE Axillary intra-aortic balloon pump therapy has been described as a bridge to transplant. Advantages over femoral intra-aortic balloon pump therapy include reduced incidence of infection and enhanced patient mobility. We identified the patients who would benefit most from this therapy while awaiting heart transplantation. METHODS We conducted a single-center, retrospective observational study to evaluate outcomes from axillary intra-aortic balloon pump therapy. These included hemodynamic parameters, duration of support, and success in bridging to transplant. We selected patients on the basis of history of sternotomy, elevated panel-reactive antibody, and small body habitus. Patients were made to ambulate aggressively beginning on postoperative day 1. RESULTS Between September 2007 and September 2010, 18 patients underwent axillary intra-aortic balloon pump therapy. All patients had the devices placed through the left axillary artery with a Hemashield side graft (Boston Scientific, Natick, Mass). Before axillary placement, patients underwent femoral placement to demonstrate hemodynamic benefit. Duration of support ranged from 5 to 63 days (median = 19 days). There was marked improvement in ambulatory potential and hemodynamic parameters, with minimal blood transfusion requirements. There were no device-related infections. Some 72% of the patients (13/18) were successfully bridged to transplantation. CONCLUSIONS Axillary intra-aortic balloon pump therapy provides excellent support for selected patients as a bridge to transplant. The majority of the patients were successfully bridged to transplant and discharged. Although this therapy has been described in previous studies, this is the largest series to incorporate a regimen of aggressive ambulation with daily measurements of distances walked.

Does Renal Dysfunction and Method of Bridging Support Influence Heart Transplant Graft Survival

BACKGROUND Renal insufficiency is common in status 1B patients supported with inotropes or a continuous flow left ventricular device (CF-LVAD) as a bridge to heart transplantation. We evaluated the association of renal function and inotrope versus CF-LVAD support on posttransplant graft survival in status 1B patients. METHODS The Scientific Registry for Transplant Recipients database was analyzed for posttransplant survival in status 1B patients bridged with inotropes or CF-LVAD who underwent transplantation between 2003 and 2012. Pretransplant renal function was measured by estimating glomerular filtration rate (GFR) and was stratified as less than 45 mL · min(-1) · 1.73 m(-2), 45 to 59, and 60 or greater. Univariate Kaplan-Meier and multivariate Cox regression models were used to evaluate the main effects of GFR strata and inotropes versus CF-LVAD, and the interaction effect of GFR strata by CF-LVAD, on graft survival. RESULTS This study included 4,158 status 1B patients (74% male, aged 53 ± 12 years). Of those, 659 patients had a CF-LVAD (HeartMate-II [Thoratec, Pleasanton, CA], n = 638; HVAD [HeartWare, Framingham, MA], n = 21), and 3,530 were receiving inotropes (31 CF-LVAD patients were also receiving inotropes). Kaplan-Meier analyses demonstrated reduced graft survival (p = 0.022) in patients with pretransplant GFR less than 45 versus GFR 45 to 59 (p = 0.062) and versus GFR 60 or greater (p = 0.007), and no effect of inotrope versus CF-LVAD support on graft survival (p = 0.402). Multivariate analysis demonstrated that, after adjusting for the main effects of GFR stratum, CF-LVAD, and inotropes, status 1B patients bridged with a CF-LVAD and GFR in the lowest stratum had reduced graft survival (interaction effect p = 0.040). CONCLUSIONS Pretransplant renal insufficiency was associated with reduced posttransplant graft survival in status 1B patients. This risk is increased for patients bridged with a CF-LVAD (versus inotropes) who have GFR in the lowest stratum.

Mechanical Circulatory Support and Heart Transplantation: Donor and Recipient Factors Influencing Graft Survival

BACKGROUND Mechanical circulatory support is an accepted strategy to bridge patients to heart transplantation (HTx). Among mechanical circulatory support patients who go on to HTx, factors associated with improved graft survival have not been fully elucidated. METHODS Using the Scientific Registry for Transplant Recipients, we identified adults who were treated with a left ventricular assist device (LVAD) or total artificial heart (TAH) before HTx. Kaplan-Meier and multivariate Cox regression models were used to identify patient, donor, and device characteristics associated with graft survival. RESULTS Between January 1997 and February 2012, 2,785 adults underwent HTx. Before HTx, 2,674 patients were treated with a LVAD (HeartMate XVE, 724; HeartMate II, 1,882; HeartWare, 68), and 111 were treated with a TAH. Follow-up averaged 25 ± 24 months. Gender mismatch occurred in 23%. Graft survival did not differ between LVAD groups (all p > 0.168), but TAH was associated with reduced graft survival compared with LVADs (p < 0.001). After controlling for device type (LVAD vs TAH), lower recipient pulmonary vascular resistance, shorter ischemic time, younger donor age, donor-to-recipient gender match, and higher donor-to-recipient body mass index ratio were independent predictors of longer graft survival (all p < 0.05). CONCLUSIONS TAH was associated with reduced graft survival after transplant, and survival did not differ between the LVAD device groups. Additional variables that were independently associated with graft survival were donor age, recipient peripheral vascular resistance, ischemic time, gender match, and donor-to-recipient body mass index ratio. Recognition of these factors may inform decisions regarding device support and donor suitability.

Perioperative Blood Product Use: A Comparison Between HeartWare and HeartMate II Devices

BACKGROUND The HeartWare (HW) (Framingham, MA) and the HeartMate II (HM II) (Thoratec Inc, Pleasanton, CA) continuous-flow left ventricular assist devices (CF-LVADs) are commonly used to bridge patients to transplantation. We hypothesized that there are differences in perioperative blood product (BP) use and chest tube (CT) output between CF-LVAD types. METHODS We retrospectively evaluated BP use in 71 patients who were implanted with a CF-LVAD (HM II = 38; HW = 33) by median sternotomy for bridge to transplantation (BTT) indications from 2009 to 2013. Detailed BP use data were collected during the intraoperative and postoperative periods and included packed red blood cells, platelets, fresh frozen plasma, and cryoprecipitate. RESULTS Preoperative characteristics (age, left ventricular ejection fraction, previous sternotomy, ischemic cause), and risk stratification scores (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS]) profile, Leitz-Miller score, Kormos score) were comparable between groups (all p > 0.05). Total average intraoperative and postoperative BP use was different between device types: HW = 8.3 ± 13 versus HM II = 12.6 ± 14.0 units (p = 0.002) and HW = 6.1 ± 12.0 units compared with HM II = 13.5 ± 24.1 units (p = 0.022), respectively. Average postoperative CT output for HW (3,231 ± 3,648 mL) and HM II (3,463 ± 3,050) (p < 0.008) were different between device types. Multivariate analysis revealed that a higher preoperative Leitz-Miller score, implantation of an HM II CF-LVAD, previous sternotomy, and a longer duration of cardiopulmonary bypass (CPB) time were independently associated with increased need for BP use, whereas only use of the HM II device and a longer bypass time predicted a greater CT output. CONCLUSIONS Compared with HM II, implantation of the HW CF-LVAD was associated with reduced intraoperative and postoperative BP use and decreased CT output. Increased awareness of device-related differences in bleeding and BP use may improve CF-LVAD patient outcomes.

Early outcomes using hepatitis C–positive donors for cardiac transplantation in the era of effective direct-acting anti-viral therapies

BACKGROUND Given the shortage of suitable donor hearts for cardiac transplantation, and the favorable safety and efficacy of current agents used to treat hepatitis C virus (HCV), our institution recently piloted transplantation of select patients using HCV-positive donors. METHODS Between September 2016 and March 2017, 12 HCV-naive patients and 1 patient with a history of treated HCV underwent heart transplantation (HT) using hearts from HCV-positive donors after informed consent. Patients who acquired HCV were referred to hepatology and treated with direct-acting anti-viral therapies (DAAs). Data collection and analysis were performed with institutional review board approval. RESULTS At the time of HT, mean age of recipients was 53 ± 10 years, and 8 patients (61.5%) were on left ventricular assist device support. After consent to consider an HCV-positive heart, mean time to HT was 11 ± 12 days. Nine of 13 patients (69%) developed HCV viremia after transplant, including 8 who completed DAA treatment and demonstrated cure, as defined by a sustained virologic response 12 weeks after treatment. One patient died during Week 7 of his treatment due to pulmonary embolism. DAAs were well tolerated in all treated patients. CONCLUSIONS In the era of highly effective DAAs, the use of HCV-positive donors represents a potential approach to safely expand the donor pool. Additional follow-up is needed to elucidate long-term outcomes.

Marginal Donor Use in Patients Undergoing Heart Transplantation With Left Ventricular Assist Device Explantation

BACKGROUND The use of continuous flow (CF) left ventricular assist devices (LVAD) as a bridge to orthotopic heart transplantation (OHT) has increased. This study examined survival outcomes after CF-LVAD explantation and OHT using marginal donors. METHODS Adults undergoing OHT with or without LVAD explant using marginal donors between 2007 and 2014 were identified in the Scientific Registry for Transplant Recipients database. A previously validated donor risk score was used to define marginal donors. Patients were stratified into four groups based on utilization of a marginal donor with or without LVAD explantation at OHT. Graft survival was analyzed at 1 and 5 years. RESULTS Overall, 7,798 patients with OHT were analyzed. Whereas 1,862 patients (24%) underwent direct OHT utilizing marginal donors, only 626 patients (30% [group A]) underwent OHT with LVAD explant (HeartMate II [Thoratec, Pleasanton, CA], n =581, 93%; HVAD [HeartWare, Framingham, MA], n = 45, 7%) and 1,236 (70%) underwent direct OHT (group B). Standard donors were utilized for 2,334 patients with CF-LVAD explant (group C), and 3,602 patients underwent direct OHT (group D). Utilization of marginal donors in patients undergoing LVAD explantation was associated with decreased posttransplant graft survival (p < 0.001). After adjusting for recipient age, sex, listing status at OHT, body mass index, creatinine, and duration of LVAD support, Cox regression analysis found that patients bridged with LVADs, recipients receiving transplants from marginal donors, recipients with highest age and body mass index, and highest creatinine were at increased risk of graft failure (all p < 0.01). CONCLUSIONS Utilization of marginal donors in patients undergoing CF-LVAD explantation and OHT is associated with reduced early and late graft survival. These findings support cautionary use of marginal donors in patients bridged with CF-LVAD.

Institutional volume of heart transplantation with left ventricular assist device explantation influences graft survival.

BACKGROUND There are increasing numbers of patients undergoing orthotopic heart transplantation (OHT) with left ventricular assist device (LVAD) explantation (LVAD explant-OHT). We hypothesized that LVAD explant-OHT is a more challenging surgical procedure compared to OHT without LVAD explantation and that institutional LVAD explant-OHT procedural volume would be associated with post-transplant graft survival. We sought to assess the impact of institutional volume of LVAD explant-OHT on post-transplant graft survival. METHODS This is a retrospective analysis of the Scientific Registry of Transplant Recipients for adult OHTs with long-term LVAD explantation. LVAD explant-OHT volume was characterized on the basis of the centers year-specific total OHT volume (OHTvol) and year-specific LVAD explant-OHT volume quartile (LVADvolQ). The effect of LVADvolQ on graft survival (death or re-transplantation) was analyzed. RESULTS From 2004 to 2011, 2,681 patients underwent OHT with LVAD explantation (740 with HeartMate XVE, 1,877 with HeartMate II and 64 with HeartWare devices). LVAD explant-OHT at centers falling in the lowest LVADvolQ was associated with reduced post-transplant graft survival (p = 0.022). After adjusting for annualized OHTvol (HR = 0.998, 95% CI 0.993 to 1.003, p = 0.515 and pulsatile XVE (HR = 0.842, 95% CI 0.688 to 1.032, p = 0.098), multivariate analysis confirmed a significantly (approximately 37%) increased risk of post-transplant graft failure among explant-OHT procedures occurring at centers in the lowest volume quartile (HR = 1.371, 95% CI 1.030 to 1.825, p = 0.030). CONCLUSION Graft survival is decreased when performed at centers falling in the lowest quartile of LVAD explant-OHT for a given year. This volume-survival relationship should be considered in the context of limited donor organ availability and the rapidly growing number of LVAD centers.

Mechanical circulatory support and simultaneous heart-kidney transplantation: An outcome analysis

BACKGROUND Single-donor simultaneous heart-kidney transplantation (SHKT) can significantly improve the survival of those with advanced heart failure and advanced renal insufficiency. Data on pre-transplant use of mechanical circulatory support (MCS) devices and outcomes after SHKT are limited and conflicting. METHODS Using the United Network for Organ Sharing registry data, we evaluated 749 adults undergoing SHKT after January 1, 2000. Patients were categorized into the following groups according to their type of pre-transplant MCS device: none (n = 568), pulsatile-flow left (n = 28), continuous-flow left (n = 68), temporary (n = 12), biventricular (n = 19), total artificial heart (n = 20), and unknown (n = 34). Regression analyses were performed to assess the association between types of MCS and post-transplant outcomes. RESULTS Pre-transplant MCS was not associated with in-hospital mortality (univariate odds ratio [OR], 1.57; 95% confidence interval [CI], 0.82-2.97; p = 0.170) or post-discharge mortality (univariate hazard ratio, 0.92; 95% CI, 0.58-1.47; p = 0.733). Patients supported with pre-transplant temporary MCS devices were more likely to suffer from serious complications (composite of cardiac or non-cardiac surgeries, stroke, any drug-treated infection, and permanent pacemaker; multivariable adjusted OR, 10.0; 95% CI, 2.77-36.0; p < 0.001) after SHKT. Pre-transplant MCS did not increase risk of post-transplant dialysis (multivariable adjusted OR, 1.19; 95% CI, 0.81-1.75; p = 0.375) or cardiac rejection (univariate OR, 0.71; 95% CI, 0.34-1.51; p = 0.382), and did not prolong the length of hospital stay (≥ 4 weeks; multivariable adjusted OR, 1.05; 95% CI, 0.69-1.59; p = 0.832). Post-transplant dialysis status was a major determinant of adverse in-hospital (multivariable adjusted OR, 6.17; 95% CI, 3.14-12.1; p < 0.001) and post-discharge (multivariable adjusted hazard ratio, 1.56; 95% CI, 1.02-2.39; p = 0.041) mortality after SHKT. CONCLUSIONS In the current transplant era, survival after SHKT in patients with pre-transplant MCS was equivalent to that of conventional SHKT. Pre-transplant dialysis, and not MCS status, determined the need for post-SHKT dialysis, which in-turn was a major risk factor for in-hospital and long-term mortality.

Gene Expression Profiling for Cardiac Rejection Surveillance is not Predictive of Post‐Transplantation Skin Cancer

BACKGROUND The risk of skin cancer in solid organ transplant recipients (SOTR) is 50 to 100 times as great as in those without a transplant. Multiple factors, including immunosuppression, influence the development of post‐transplantation skin cancer. Individuals with cardiac transplant are serially screened for organ rejection and immunosuppressive regimen effectiveness. Gene expression profiling of peripheral blood mononuclear cells has been established as a noninvasive test for monitoring cardiac rejection. OBJECTIVE We examined individuals with cardiac transplant monitored using peripheral gene expression profiling to determine whether the profile of peripheral blood mononuclear cell activity could correlate with the development of post‐transplantation skin cancer. METHODS AND MATERIALS Sixty‐one patient records were examined for initial endomyocardial biopsy results, gene expression profiling data, immunosuppressive regimens, and post‐transplantation skin cancer. RESULTS There was no relationship between acute rejection and the development of skin cancer. No relationship between peripheral gene expression profiling and the development of post‐transplantation skin cancer was observed. The most common skin cancer in the population was squamous cell carcinoma. SOTR suppressed with azathioprine had a significantly higher incidence of squamous cell carcinoma. CONCLUSION Although gene expression tests have advanced transplant surveillance, they were not associated with post‐transplantation skin cancer.