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CIED Removal in LVAD Infections Introduction Heart failure patients with left ventricular assist devices (LVADs) are at risk for infection. Cardiac implantable electronic devices (CIEDs) are commonly present in these patients. The course of infections in patients with an LVAD and a CIED is not well described. Methods and Results We identified 6 patients with a durable LVAD that underwent CIED removal because of an LVAD associated infection (LVADI). Patient and infection characteristics, management strategy, and clinical outcomes are described. All 6 patients were male, and the mean age was 59.6 years (range 43–72). Four of 6 patients had an ischemic cardiomyopathy, and 3 patients were diabetic. The median creatinine clearance for patients was 40.5 mg/dL (range 19–65). Five of 6 patients had a continuous flow LVAD placed as destination therapy. Four of 6 patients had a previous LVADI managed medically before the current infection leading to CIED removal. The indication for CIED removal was a bloodstream infection in 5 of 6 patients. Three of these patients had potential vegetations identified by echocardiography on device leads. The mean implanted age of the removed leads was 62 months (range 1–179), and 1 of the 6 patients experienced a procedural complication (hematoma) from CIED removal. Four of 6 patients that underwent CIED removal for an LVADI had recurrence of infection. Five of 6 patients died during the initial presentation or from repeat presentation for infection. Conclusion Despite CIED removal for an LVADI, recurrent infections are common and mortality remains high.

ABO dependent variation in von Willebrand factor (vWf) and procoagulant factor VIII (FVIII) is a plausible mechanism for modulating perioperative hemostasis and bleeding. Group AB has the highest and group O the lowest vWf and FVIII levels. Therefore, we tested the hypothesis that ABO blood group is associated with perioperative transfusion and subsequent survival after coronary revascularization. This retrospective study combined demographic, operative, and transfusion data, including follow-up for a median of 2,096 days, for consecutive aortocoronary bypass (CABG) and CABG/valve procedures from 1996–2009 at a tertiary referral University Heart Center. Between group differences were compared by a Kruskall Wallis test, and hazard ratios [95 % confidence intervals] are reported for mortality risk-adjusted Cox proportional hazards regression analysis. From 15,454 patients, follow-up records were available for 13,627 patients: 6,413 group O, 5,248 group A, 1,454 group B, and 435 group AB. Packed red blood cells were the most commonly transfused blood product (3 [0–5] units), while group AB received 2 [0–5] units (Kruskall Wallis Chi squared value for between group differences = 8.2; p = 0.04). Group AB favored improved long-term, postoperative survival (Hazard ratio = 0.82 [95 %CI 0.68–0.98]; p = 0.03), which became evident approximately a year after surgery. In conclusion, the procoagulant phenotype of blood group AB is associated with fewer transfusions and improved late survival after cardiac surgery. Whether this finding is related to fewer perioperative transfusions, a reduction in later bleeding or other mechanisms remains speculative.

As increasing numbers of elderly people undergo cardiac surgery, neurologists are frequently called upon to assess patients with neurological complications from the procedure. Some complications mandate acute intervention, whereas others need longer term observation and management. A large amount of published literature exists about these complications and guidance on best practice is constantly changing. Similarly, despite technological advances in surgical intervention and modifications in surgical technique to make cardiac procedures safer, these advances often create new avenues for neurological injury. Accordingly, rapid and precise neurological assessment and therapeutic intervention rests on a solid understanding of the evidence base and procedural variables.

Background Although atrial arrhythmias (AAs) are common in heart failure, the incidence of AAs subsequent to the placement of left ventricular assist devices (LVADs) has not been elucidated. Methods Patients receiving a HeartMate II LVAD in the bridge to transplant (n = 490) and destination therapy (n = 634) trials were included (n = 1125). AAs requiring treatment were recorded, regardless of symptoms. Using Cox models with and without a 60-day blanking period, risk factors for early and late AAs were determined. Results In total, there were 271 AAs in 231 patients (21%), most of which occurred within the first 60 days. Patients with and without AAs had similar survival (p = 0.16). Serum creatinine (hazard ratio [HR] = 1.49 per unit increase, 1.18 to 1.88; p

ObjectivesThis study sought to examine trends in mortality, readmission, and costs among Medicare beneficiaries receiving ventricular assist devices (VADs) and associations between hospital-level procedure volume and outcomes.BackgroundVADs are an option for patients with advanced heart failure, but temporal changes in outcomes and associations between facility-level volume and outcomes are poorly understood.MethodsThis is a population-based, retrospective cohort study of all fee-for-service Medicare beneficiaries with heart failure who received an implantable VAD between 2006 and 2011. We used Cox proportional hazards models to examine temporal changes in mortality, readmission, and hospital-level procedure volume.ResultsAmong 2,507 patients who received a VAD at 103 centers during the study period, the in-hospital mortality decreased from 30% to 10% (p < 0.001), the 1-year mortality decreased from 42% to 26% (p < 0.001), and the all-cause readmission was frequent (82% and 81%; p = 0.70). After covariate adjustment, in-hospital and 1-year mortality decreased (p < 0.001 for both), but the all-cause readmission did not change (p = 0.82). Hospitals with a low procedure volume had higher risks of in-hospital mortality (risk ratio: 1.72; 95% confidence interval [CI]: 1.28 to 2.33) and 1-year mortality (risk ratio: 1.55; 95% CI: 1.24 to 1.93) than high-volume hospitals. Procedure volume was not associated with risk of readmission. The greatest cost was from the index hospitalization and remained unchanged ($204,020 in 2006 and $201,026 in 2011; p = 0.21).ConclusionsShort- and long-term mortality after VAD implantation among Medicare beneficiaries improved, but readmission remained similar over time. A higher volume of VAD implants was associated with lower risk of mortality but not readmission. Costs to Medicare have not changed in recent years.

Objectives This study sought to determine the pre-operative risk factors related to late bleeding, stroke, and pump thrombosis in patients with HeartMate II (HMII) left ventricular assist devices (LVADs) (Thoratec Corporation, Pleasanton, California) that might influence tailored improvements in patient management. Background Adverse events in LVAD patients remain high. It is unclear whether pre-operative characteristics influence the likelihood of the development of post-operative hemorrhagic or thrombotic complications. Knowing which patients are at greater risk might assist in tailoring anticoagulation therapy for certain patients. Methods Advanced heart failure patients (n = 956) discharged from the hospital after LVAD implantation in the HMII bridge to transplantation (n = 405) and destination therapy (n = 551) clinical trials were retrospectively evaluated. Bleeding requiring surgery or transfusion of >2 U of packed red blood cells, stroke (hemorrhagic and ischemic), and pump thrombosis were tracked from hospital discharge until patient outcome. Results Adverse event rates for post-discharge bleeding (0.67 events/patient-year) were higher than those for hemorrhagic stroke (0.05), ischemic stroke (0.04), and pump thrombosis (0.03). The main sites of bleeding included gastrointestinal (45% of events), wound (12%), and epistaxis (4%). Older age (>65 years) (hazard ratio [HR]: 1.31), lower pre-operative hematocrit (≤31%) (HR: 1.31), ischemic etiology (HR: 1.35), and female (HR: 1.45) were statistically significant multivariable risk factors for bleeding. Female (HR: 1.92) and 65 years of age and younger (HR: 1.94) were multivariable risk factors for hemorrhagic stroke, whereas female (HR: 1.84) and history of diabetes (HR: 1.99) were risk factors for ischemic stroke. Female (HR: 1.90) and higher body mass index (HR: 1.71/10 kg/m 2 increase) were also multivariable risk factors for pump thrombosis. Conclusions The risk of bleeding and thrombotic events during LVAD support differs by patient demographics, including sex, age, body mass index, and etiology of heart failure. Further studies should focus on the potential of tailored anticoagulation strategies in these subgroups.

Background Preexisting valve pathology is common in patients with end-stage heart failure undergoing left ventricular assist device (LVAD) placement. The indications and subsequent benefits of performing valvular procedures in these patients are unclear. The objective of this study was to determine the impact of performing concurrent surgical valve procedures in a large cohort of patients receiving LVADs. Methods One thousand one hundred six patients received the HeartMate II (HMII) LVAD in the bridge to transplant (n = 470) and destination therapy (n = 636) clinical trials. Of these, 374 patients (34%) had concurrent cardiac surgery procedures as follows: 242 patients (21%) with 281 concurrent valve procedures (VP) (aortic 80, mitral 45, and tricuspid 156), and 641 patients had only HMII LVAD. The focus of this study was to determine the clinical outcomes of patients undergoing HMII + VP compared with those who received HMII alone. Results Patients undergoing HMII + VP were significantly older, had higher blood urea nitrogen levels and central venous pressure, and decreased right ventricular stroke work index; intraoperatively, the median cardiopulmonary bypass times were also longer. The unadjusted 30-day mortality was significantly higher in patients undergoing HMII + VP (10.3% vs 4.8% for LVAD alone, P = .005). Subgroup analysis of individual VPs showed that higher mortality occurred in patients with HMII plus 2 or more VPs (13.5%, P = .04) followed by trends for increased mortality with HMII plus mitral alone (11.5%, P = NS), HMII plus aortic alone (10.9%, P = NS), and HMII plus tricuspid (8.9%, P = NS) procedures. Of these various groups, only patients undergoing HMII + isolated aortic VP ( P = .001) and HMII + multiple VPs ( P = .046) had significantly worse long-term survival compared with patients undergoing HMII alone. Right heart failure and right ventricular assist device use was increased in patients undergoing VPs, but there was no difference in the incidence of bleeding or stroke. Conclusions Patients frequently require concurrent VPs at the time of LVAD placement; these patients are sicker and have higher early mortality. Furthermore, right ventricular dysfunction is increased in these patients. Further studies to develop selection criteria for concurrent valve interventions are important to further improve clinical outcomes.

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.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.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 (p0.0001). Multivariable hazard function analysis showed risk factors for pump thrombosis included later implant year (p0.0001), younger age (p0.0001), 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 (p0.0001). Survival (p0.0001) and freedom from infection (p = 0.008) and cerebrovascular accident (p0.0001) were lower after pump exchange than after primary implant.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.

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: Is there a role for upper-extremity intra-aortic balloon pump counterpulsation (UE-IABP) in the treatment of end-stage heart failure? Altogether 230 papers were found using the reported search, of which 6 papers represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Of the 163 bridge-to-transplantation (BTT) patients, 141 (86.5%) were successfully transplanted and of the 9 bridge-to-recovery (BTR) patients, 6 (66.7%) were successfully weaned from the device. Length of support ranged from 3 to 152 days, and the most frequent complications were device malfunction or migration necessitating exchange or repositioning, occurring at a collective rate of 37.3%. UE-IABP is a minimally invasive and cost-effective strategy that provides haemodynamic support while preserving both the mediastinum and the functional status in BTR and BTT patients who may not tolerate more invasive modes of mechanical circulatory support. We conclude that UE-IABP can be used as a bridge-to-recovery (BTR) or transplant (BTT) in patients with end-stage heart failure.

Continuous-flow left ventricular assist systems increase the rate of survival among patients with advanced heart failure but are associated with the development of pump thrombosis. We investigated the effects of a new magnetically levitated centrifugal continuous-flow pump that was engineered to avert thrombosis.We randomly assigned patients with advanced heart failure to receive either the new centrifugal continuous-flow pump or a commercially available axial continuous-flow pump. Patients could be enrolled irrespective of the intended goal of pump support (bridge to transplantation or destination therapy). The primary end point was a composite of survival free of disabling stroke (with disabling stroke indicated by a modified Rankin score3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove the device at 6 months after implantation. The trial was powered for noninferiority testing of the primary end point (noninferiority margin, -10 percentage points).Of 294 patients, 152 were assigned to the centrifugal-flow pump group and 142 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 131 patients (86.2%) in the centrifugal-flow pump group and in 109 (76.8%) in the axial-flow pump group (absolute difference, 9.4 percentage points; 95% lower confidence boundary, -2.1 [P0.001 for noninferiority]; hazard ratio, 0.55; 95% confidence interval [CI], 0.32 to 0.95 [two-tailed P=0.04 for superiority]). There were no significant between-group differences in the rates of death or disabling stroke, but reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (1 [0.7%] vs. 11 [7.7%]; hazard ratio, 0.08; 95% CI, 0.01 to 0.60; P=0.002). Suspected or confirmed pump thrombosis occurred in no patients in the centrifugal-flow pump group and in 14 patients (10.1%) in the axial-flow pump group.Among patients with advanced heart failure, implantation of a fully magnetically levitated centrifugal-flow pump was associated with better outcomes at 6 months than was implantation of an axial-flow pump, primarily because of the lower rate of reoperation for pump malfunction. (Funded by St. Jude Medical; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).

Saphenous vein graft aneurysms after coronary artery bypass grafting (CABG) have been rarely reported. Their incidence and natural history are poorly defined. Herein, we present a patient who presented acutely with contained rupture of a large saphenous vein graft aneurysm 12 years after CABG, which was successfully managed with open aneurysm resection and regrafting.

Background Ventricular assist devices (VADs) are increasingly used for the management of end-stage heart failure, but infection is a complication that has not been thoroughly studied. The purpose of our study was to compare patients who had surgical debridement vs. medical therapy alone for VAD-related/specific infections. Methods We performed a retrospective chart review on patients at Duke University Hospital (DUH) from 2015 to 2017. Patients with VAD-related/specific infections were included, per 2011 ISHLT definitions. We reviewed electronic medical records for demographics, VAD implantation data, infectious episodes, surgical debridements and mortality. Descriptive statistics compared patients with and without debridement and compared with and without relapse. Results We found 94 infections in 72 patients. Descriptive statistics of the cohort and comparisons with and without debridement can be seen in Table 1. Sixty-one cases (65%) included debridement and 5 (5%) required pump exchange. Notably, patients with fever or bacteremia were more likely to undergo debridement. Of the patients that had a preoperative CT, sensitivity for deep infection (pump, pocket, or deep to the muscle) was 38%, yet specificity was 95%. For superficial infections (involving the driveline or superficial to the muscle), preoperative CT sensitivity was 95%; specificity 65%. Table 2 shows intraoperative culture data. When the preoperative driveline culture grew Staphylococcus species or Pseudomonas aeruginosa there was strong correlation with intraoperative organism (matched in >75% of cases). Table 3 compares treatments among patients with and without infective relapse. Relapse rate appeared the same if patients received 2, 4, or ≥6 weeks of intravenous antibiotics. Conclusion We present a large single-center cohort [DCWM1] examining VAD-related/-specific infections. While patients chosen for debridement may be sicker, these patients had a longer hospital stay and relapsed more often. Preoperative CT should be used with caution as it underestimates the extent of disease. However, preoperative driveline cultures correlated strongly with intraoperative cultures for most common pathogens. There was no association between initial intravenous therapy duration and infection relapse. Table 1. demographic characteristics of total cohort and comparisons among patients who underwent debridement for treatment of infection and patients who did not undergo debridement for treatment of infection Table 2. Organisms found intraoperatively and the number of organisms found preoperatively that are the same as the intraoperative cultures Table 3. Comparing treatment and cultures in patients who suffered an infection relapse Disclosures All authors: No reported disclosures.

Purpose There remains an urgent need to expand the donor pool for thoracic organ transplant recipients. Utilizing donors who are actively viremic with hepatitis C (HCV) is rapidly becoming standard practice, although no consensus exists regarding when to treat post-transplant, with which drug, and for how long. Cost remains an issue with direct acting antivirals (DAA). Hepatitis B (HBV) viremic donors are predicted to become more common. We designed and implemented a protocol to utilize HCV and HBV NAT+ donors. Methods We designed an open-label, ongoing safety and efficacy protocol to allow all transplant programs at our center, adult and pediatric, to enroll patients for whom there is an emergent need to expand the donor pool. Patients are consented and stratified into 2 groups: those who received NAT+ donors vs NAT- donor comparators. Patients are followed for a minimum of 12m post-transplant, with hepatitis viral loads measured at d5, 10 and 21 (and at clinical discretion thereafter). The primary end points are 3, 12month graft and patient survival. Secondary end points include viral cure rates, therapy associated adverse events, attributable hepatitis mortality, functional status, rejection rates and time to transplantation. HCV therapy of choice is started after discharge, or if needed urgently, begun inpatient and paid for by the hospital. HBV therapy is initiated at the time of transplantation. The protocol is monitored by a Data Safety Monitoring Board. Results 11 pts have enrolled to date and progressed to NAT+ transplant, including 8 adult heart transplants, 1 bilateral lung, 1 heart-lung and 1 lung-liver transplant. All have received HCV-viremic donors, within 1 month of consent. Median age is 56yrs (range 25-72). 3 recipients were HCV-viremic pre-transplant, 8 were HCV-naive. All 8 D+/R- pts became infected with HCV, 7 were actively viremic by day 5, one became viremic at d21. 9/9 patients are alive at 3months, with HCV therapy having been initiated in 6, and SVR12 achieved in 5 to date. So far we report 100% grafts survival, and no adverse events attributable to hepatitis. 1 patient required HCV therapy initiation in the hospital. Conclusion We present real world experience about the implementation of a protocol allowing HCV and HBV NAT+ donors to be used for thoracic and multivisceral transplants. Using a multidisciplinary approach, our protocol offers a means to expand the thoracic organ donor pool safely.

Purpose A shortage of donor hearts and high waiting list mortality have resulted in many transplant centers pursuing alternate strategies for utilization of adult donor hearts. Programs in Europe and Australia have demonstrated success with heart transplantation following donation after circulatory death (DCD); however, there are no active DCD heart transplant centers in the US. The aim of this study is to evaluate the potential impact of DCD donors on the US heart transplant donor pool. Methods The 2005-2017 UNOS/OPTN registry was retrospectively reviewed for all deceased donors. Potential donors who did not donate any organ for transplant were excluded. A multivariable logistic regression model for successful heart transplantation among donation after brain death (DBD) donors was generated using relevant demographic and clinical characteristics based on clinical experience. Covariates included donor age, gender, BMI, ethnicity, medical history, and ABO blood type. This model was then applied to Maastricht 3 DCD donors of other organs to identify suitable donors for heart transplantation. Results A total of 73,119 DBD donors and 12,148 DCD donors from 2005-2017 met inclusion criteria. Among the DBD donors, 30,422 (41.6%) were used for heart transplantation and 42,697 (58.4%) were not. Logistic regression identified independent predictors of successful heart transplantation. After applying this model to suitable DCD donors, an additional 5,271 potentially eligible heart transplant donors were identified during the study period, including 671 in 2016 alone. The supply of potential DCD hearts has increased annually (Figure). Conclusion DCD donation in heart transplantation has the potential to increase the pool of donor organs by approximately 20% per year in the United States.

Purpose Heart transplantation is limited by the supply of donor organs. Previous studies have associated donor/recipient gender mismatch with decreased post-transplant survival and increased rates of primary graft dysfunction. We evaluate whether this risk can be mitigated. Methods We performed a retrospective analysis of the OPTN/UNOS registry encompassing years 1987 to 2018 for all male adult recipients (>18 years) who underwent isolated heart transplantation with grafts from female donors. Comparison was made to transplants from male donors. Recipients were primarily stratified into two groups, those with BMI less than or greater than donor BMI. Patients were stratified by BSA on secondary analysis. Kaplan-Meier analysis was used to estimate survival post-transplant. Cox Proportional Hazards modeling was performed to identify independent predictors of survival. Results A total of 8,232 candidates met inclusion criteria. Male recipients receiving hearts from higher BMI female donors were more likely to be in the ICU pre-transplant (39.5% vs 36.6%, p = 0.001), on IV inotropes at listing (35.7% vs 33.0%, p = 0.013), and were less likely to have a history of diabetes (21.4% vs 23.9%, p = 0.012). On Kaplan-Meier analysis, recipients transplanted with hearts from higher BMI female donors had improved overall survival. When stratified by BSA (Figure 1), male recipients transplanted with hearts from higher BSA female donors had similar post-transplant survival as male recipients who received hearts from male donors. On Cox Proportional Hazards analysis, increased donor BMI/BSA relative to recipient BMI/BSA remained an independent predictor of improved survival (p Conclusion Prior studies have associated transplanting hearts from female donors into male recipients with decreased post-transplant survival. In this study we have demonstrated that this may be mitigated by matching grafts from female donors to male recipients with lower BMI and especially BSA.

Purpose Older donors are increasingly used in an effort to expand the donor pool in heart transplantation. We used the UNOS registry to examine the impact of older donors on the survival of recipients of different ages. Methods The UNOS/OPTN registry (2005-2017) was interrogated for adult patients who successfully underwent an initial heart transplant without other simultaneous transplants. Donors and recipients in the highest quartile of age were labeled as older, and those below this threshold were labeled younger. Four groups of donor-recipient pairs were created: (1) younger donor and younger recipient, (2) younger donor and older recipient, (3) older donor and younger recipient, and (4) older donor and older recipient. Overall survival was analyzed using Kaplan Meier and Cox proportional hazards models. Results A total of 23,750 patients met inclusion criteria. Donors and recipients over the age of 42 and 61 were defined as older, respectively. Older recipients were more likely to be Caucasian, have diabetes, and have malignancy. Older donors were more likely to be female, Caucasian, have a history of smoking, hypertension, and cancer, and have died from a stroke. Median survival in groups 1, 2, 3, and 4 was 13, 11, 12, and 10 years, respectively. In unadjusted and multivariable analyses, old donors were associated with worse survival compared to younger donors in both older and younger recipients (Fig. 1). Compared to group 1, group 3 (hazard ratio [HR] 1.31; 95% confidence interval [CI] 1.22, 1.40) had worse survival. Compared to group 2, group 4 (HR 1.31; 95%CI 1.24, 1.39) had worse survival. Compared to group 1, groups 3 (HR 1.35; 95%CI 1.26, 1.46), and 4 (HR 1.70; 95%CI 1.55, 1.86) had worse survival. Causes of death were similar across groups. Conclusion Donors over the age of 42 are associated with worse survival compared to younger donors in both younger and older recipients after heart transplant. Further research is needed to optimize allocation and use of older donor organs.

Purpose The transplantation of hearts from traumatically brain-injured (TBI) donors has been associated with inferior long-term survival. The purpose of this study was to explore the outcomes of heart transplantation using TBI donors in a large national registry. Methods We performed a retrospective cohort analysis of the OPTN/UNOS registry encompassing years 1987 to 2018 for adult candidates (>18 years) waitlisted for isolated heart transplantation. Recipients were stratified into two groups, TBI and non-TBI donors. Propensity score matching was performed across key baseline demographic variables and a 1:1 match was done. Kaplan-Meier analysis was used to estimate survival post-transplant. Cox Proportional Hazards modeling was performed to identify independent predictors of survival. Results A total of 58,474 candidates met inclusion criteria. TBI was the leading cause of death in the donor population. Non-TBI donors (N=27,483) were more likely female (41.6% vs 18.8%, p Conclusion In the largest analysis of heart transplants and their survival according to the type of donor injury: TBI vs non-TBI, we found similar survival in heart transplant recipients. These findings should relieve concerns regarding using this unique donor population in heart transplantation.

Purpose LVAD patients with right ventricular (RV) dysfunction are prioritized on the heart transplant waiting list, however the post-transplant survival of this group is less well characterized. We aimed to determine RV dysfunction effect on post-operative survival. Methods We performed a retrospective review of the 2005-2018 OPTN/UNOS registry for candidates ≥ 18 years of age waitlisted for first-time isolated heart transplantation post LVAD implantation. Candidates were stratified based upon having RV dysfunction defined as having liver dysfunction or by the need for RVAD or IV inotropes. Results 8,379 candidates met inclusion criteria including 978 LVAD BTT patients with RV dysfunction and 7,401 BTT patients without. Compared with non-RV dysfunction patients, LVAD BTT patients with RV dysfunction were younger (median age 53 vs 56, p 0.05). Pre-transplant liver dysfunction, however, was an independent predictor of worse survival (HR 1.56, 95% CI 1.30-1.86, p Conclusion Pre-heart transplant RV failure in LVAD BTT patients is associated with decreased post-transplant survival. This survival difference is driven primarily by pre-transplant liver failure likely reflecting increased severity of RV dysfunction. While these patients currently have priority in organ allocation, future studies should evaluate candidate optimization prior to organ acceptance to improve post-transplant outcomes, particularly among patients showing signs of liver failure

Objective To use novel statistical methods for analyzing the effect of lesion set on (long-standing) persistent atrial fibrillation (AF) in the Cardiothoracic Surgical Trials Network trial of surgical ablation during mitral valve surgery (MVS). Methods Two hundred sixty such patients were randomized to MVS + surgical ablation or MVS alone. Ablation was randomized between pulmonary vein isolation and biatrial maze. During 12 months postsurgery, 228 patients (88%) submitted 7949 transtelephonic monitoring (TTM) recordings, analyzed for AF, atrial flutter (AFL), or atrial tachycardia (AT). As previously reported, more ablation than MVS-alone patients were free of AF or AF/AFL at 6 and 12 months (63% vs 29%; P Results Estimated freedom from AF/AFL/AT on any transmission trended higher after biatrial maze than pulmonary vein isolation (odds ratio, 2.31; 95% confidence interval, 0.95-5.65; P = .07) 3 to 12 months postsurgery; estimated AF/AFL/AT load (ie, proportion of TTM strips recording AF/AFL/AT) was similar (odds ratio, 0.90; 95% confidence interval, 0.57-1.43; P = .6). Within 12 months, estimated prevalence of AF/AFL/AT by TTM was 58% after MVS alone, and 36% versus 23% after pulmonary vein isolation versus biatrial maze (P Conclusions Statistical modeling using TTM recordings after MVS in patients with (long-standing) persistent AF suggests that a biatrial maze is associated with lower AF/AFL/AT prevalence, but not a lower load, compared with pulmonary vein isolation. The discrepancy between AF/AFL/AT prevalence assessed at 2 time points by Holter monitoring versus weekly TTM suggests the need for a confirmatory trial, reassessment of definitions for failure after ablation, and validation of statistical methods for assessing atrial rhythms longitudinally.

Background and Purpose— Neurocognitive decline occurs frequently after cardiac surgery and persists in a significant number of patients. Magnesium is thought to provide neuroprotection by preservation of cellular energy metabolism, blockade of the N-methyl-D-aspartate receptor, diminution of the inflammatory response, and inhibition of platelet activation. We therefore hypothesized that intraoperative magnesium administration would decrease postoperative cognitive impairment. Methods— After approval by the Duke University Health System Institutional Review Board, 389 patients undergoing cardiac surgery were enrolled in this prospective, randomized, double-blind, placebo-controlled clinical trial. Subjects were randomized to receive magnesium as a 50 mg/kg bolus followed by another 50 mg/kg infusion for 3 hours or placebo bolus and infusion. Cognitive function was assessed preoperatively and again at 6 weeks postoperatively using a standardized test battery. Mean CD11b fluorescence and percentage of platelets expressing CD62P, which are markers of leukocyte and platelet activation, respectively, were assessed by flow cytometry as a secondary outcome. The effect of magnesium on postoperative cognition was tested using multivariable regression modeling, adjusting for age, years of education, baseline cognition, sex, race, and weight. Results— Among the 389 allocated subjects (magnesium: n=198; placebo: n=191), the incidence of cognitive deficit in the magnesium group was 44.4% compared with 44.9% in the placebo group ( P =0.93). The cognitive change score and platelet and leukocyte activation were also not different between the groups. Multivariable analysis revealed a marginal interaction between treatment group and weight such that heavier subjects receiving magnesium were less likely to have cognitive deficit ( P =0.06). Conclusions— Magnesium administered intravenously during cardiac surgery does not reduce postoperative cognitive dysfunction. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00041392.

Background Intraoperative autologous platelet (PLT) collection as part of a multimodal blood conservation program carries a Class IIa recommendation from the Societies of Thoracic Surgeons and Cardiovascular Anesthesiologists, but achieving a suitable PLT yield limits its application. A novel, autologous, intraoperative, high-yield plateletpheresis collection program was established and retrospectively analyzed to identify potential improvements over previously reported plateletpheresis protocols. Study design and m-ethods Targeting complex cardiothoracic surgery patients without recent anti-PLT agents, thrombocytopenia, or severe anemia, the program aimed to achieve a PLT yield of at least one standard apheresis unit (3.0 × 10(11) ) within 60 to 90 minutes and using an automated plateletpheresis device (Trima, Terumo BCT). Anesthetized and invasively monitored patients underwent plateletpheresis via a large-bore, indwelling central line placed for the surgery. Collection-related data for quality control purposes and subsequent PLT transfusion requirements were analyzed and reported. Results Forty-two patients donated autologous PLTs between 2011 and 2012. PLT yield was 4.5 (3.9-5.0) × 10(11) , which significantly exceeds previously reported yields, and procedure duration was 53.2 (48.4-57.9) minutes. As anticipated, postcollection PLT count decreased from 268 (242-293) × 10(9) to 182 (163-201) × 10(9) /L; hypocalcemia was minimized by infusion of 1 g of CaCl2 . Autologous PLT yield was inversely correlated with allogeneic PLT use, and avoidance of allogeneic PLT transfusion was increased when the autologous yield was the equivalent of 2 or more apheresis units. Conclusion High-yield, intraoperative autologous PLT collection is achievable using an automated plateletpheresis device. Initial experience shows a reduction in reliance on allogeneic PLTs for complex cardiothoracic surgery.

Objective Compared with median sternotomy, a right thoracotomy (RT) approach to mitral surgery is associated with decreased postoperative acute renal failure. Therefore, we examined propensity-matched patients with chronic renal impairment to compare outcomes. Methods A retrospective review at a single institution identified patients who underwent mitral valve surgery from 1986 to 2010. After excluding patients who had procedures that were not usually performed through an RT approach, 2306 patients were identified. Of this group, we found 446 patients with preoperative creatinines of 1.3 mg/dL or greater. Using propensity score matching based on comorbidities, operative year, and surgeon, 90 matched patients in each group were included. Results There was no difference in the median year of operation. Postoperative mortality is 20% lower for the RT group ( P = 0.037) using Mantel-Cox statistics. This greater survival in the RT group occurred early within the first year and was maintained on long-term follow-up. The RT approach was also associated with a Cox proportional hazard for mortality of 0.528 ( P = 0.006). Incidence of postoperative complications with an RT approach was lower in terms of acute renal failure (10% vs 21%, P = 0.05), stroke (1% vs 9%, P = 0.017), and permanent pacemaker insertion (3% vs 11%, P = 0.044). Right thoracotomy was associated with lower chest tube outputs (503 vs 1333 mL, P < 0.001). Conclusions The RT approach was associated with lower postoperative mortality and morbidity in patients with impaired renal function. The RT approach to the mitral valve may be preferred in this high-risk population.

Ischemic cardiovascular disease remains the leading cause of death worldwide. Despite advances in the medical management of atherosclerosis over the past several decades, many patients require arterial revascularization to reduce mortality and alleviate ischemic symptoms. Technological advancements have led to dramatic increases in the use of percutaneous and endovascular approaches, yet surgical revascularization (bypass surgery) with autologous vein grafts remains a mainstay of therapy for both coronary and peripheral artery disease. Although bypass surgery is highly efficacious in the short term, long-term outcomes are limited by relatively high failure rates as a result of intimal hyperplasia, which is a common feature of vein graft disease. The supply of native veins is limited, and many individuals require multiple grafts and repeat procedures. The need to prevent vein graft failure has led to great interest in gene therapy approaches to this problem. Bypass grafting presents an ideal opportunity for gene therapy, as surgically harvested vein grafts can be treated with gene delivery vectors ex vivo , thereby maximizing gene delivery while minimizing the potential for systemic toxicity and targeting the pathogenesis of vein graft disease at its onset. Here we will review the pathogenesis of vein graft disease and discuss vector delivery strategies and potential molecular targets for its prevention. We will summarize the preclinical and clinical literature on gene therapy in vein grafting and discuss additional considerations for future therapies to prevent vein graft disease.

Objective Coronary artery bypass grafting with multiple internal thoracic artery grafts is currently controversial. This study assessed single institutional outcomes with multiple internal thoracic artery grafting for guidance with future clinical decisions. Methods In 19,482 patients undergoing multivessel coronary artery bypass grafting (1984-2009), baseline characteristics were recorded in a prospective databank, and follow-up was obtained by questionnaires, phone contact, or National Death Index. Outcomes examined were subsequent myocardial infarction, percutaneous coronary intervention, reoperative coronary artery bypass grafting, all-cause death, and a composite of the 4. Three groups were defined: (1) no internal thoracic artery graft (1874/19,482 or 9%); (2) single internal thoracic artery grafts and adjunctive venous conduits (single internal thoracic artery; 16,881/19,482 or 87%); and (3) multiple internal thoracic artery grafts (728/19,482 or 4%). Multivariable Cox modeling adjusted for differences in baseline characteristics, and comparisons were performed using area under the curve analysis. Results Differences in baseline characteristics for the no internal thoracic artery graft, single internal thoracic artery, and multiple internal thoracic artery groups were as follows: median age 66, 64, and 59 years, respectively; congestive heart failure 22%, 18%, and 13%, respectively; ejection fraction 0.50, 0.52, and 0.51, respectively; reoperation 10%, 3%, and 7%, respectively; diabetes 27%, 30%, and 15%, respectively; and female gender 33%, 28%, and 20%, respectively. No differences existed in the median number of diseased vessels (3, 3, and 3, respectively) or number of grafts per patient (3, 3, and 3, respectively). Composite outcome improved with increasing internal thoracic artery grafts, whether assessing unadjusted or risk-adjusted data. Compared with no internal thoracic artery graft, the adjusted hazard ratio was 0.79 (confidence interval, 0.74-0.83) for single internal thoracic artery grafting and 0.70 (confidence interval, 0.62-0.80) for multiple internal thoracic artery grafting (both P 001), reducing risk by 21% and 30%, respectively. Conclusions This study confirms improved patient outcomes with multiple internal thoracic artery grafting, achieving half again as much benefit as single internal thoracic artery grafting alone. The data suggest that increasing application of multiple internal thoracic artery grafting should be encouraged to mitigate the inherent risks and costs of long-term cardiac events.

Background Although continuous-flow left ventricular assist devices (LVAD) are durable and reliable, device replacement will be inevitable in some patients. We evaluated the incidence and outcomes of pump replacement procedures with the HeartMate II (Thoratec Corporation, Pleasanton, CA) LVAD. Methods Data were obtained from 1,128 patients implanted from March 2005 to January 2010 with the HeartMate II during the clinical trials for bridge to transplant and destination therapy. The operative mortality associated with the replacement procedure was determined. Results The mean duration of HeartMate II support was 568 ± 535 days (cumulative duration: 1,755 patient-years, longest: 6.5 years). A total of 72 (6.4%) patients underwent 79 LVAD replacements (0.045 events/patient-year) of which 2 were in the initial operation and 77 in separate procedures. Reasons for replacement were percutaneous lead damage (36 events, 3.0%), device thrombosis (25 events, 2.1%), infection (7 events, 0.6%), and miscellaneous other (11 events, 0.9%). The median time to pump replacement was 428 days (range 0 to 1,474). Of the 77 replacement procedures, there were 5 (6.5%) operative deaths within 30 days. The causes of death were device thrombosis, right heart failure, multisystem organ failure, and bleeding. One year after exchange (median 2.1 years after initial implant), 30% had died, 5% were transplanted, and 65% were ongoing and alive. Conclusions HeartMate II device failure requiring pump replacement is infrequent, but when required can be done safely. These data continue to provide encouraging evidence supporting HeartMate II use for long-term circulatory support.

Background Nontuberculous mycobacteria (NTM) commonly colonize municipal water supplies and cause healthcare-associated outbreaks. We investigated a biphasic outbreak of Mycobacterium abscessus at a tertiary care hospital. Methods Case patients had recent hospital exposure and laboratory-confirmed colonization or infection with M. abscessus from January 2013 through December 2015. We conducted a multidisciplinary epidemiologic, field, and laboratory investigation. Results The incidence rate of M. abscessus increased from 0.7 cases per 10000 patient-days during the baseline period (January 2013-July 2013) to 3.0 cases per 10000 patient-days during phase 1 of the outbreak (August 2013-May 2014) (incidence rate ratio, 4.6 [95% confidence interval, 2.3-8.8]; P < .001). Thirty-six of 71 (51%) phase 1 cases were lung transplant patients with positive respiratory cultures. We eliminated tap water exposure to the aerodigestive tract among high-risk patients, and the incidence rate decreased to baseline. Twelve of 24 (50%) phase 2 (December 2014-June 2015) cases occurred in cardiac surgery patients with invasive infections. Phase 2 resolved after we implemented an intensified disinfection protocol and used sterile water for heater-cooler units of cardiopulmonary bypass machines. Molecular fingerprinting of clinical isolates identified 2 clonal strains of M. abscessus; 1 clone was isolated from water sources at a new hospital addition. We made several water engineering interventions to improve water flow and increase disinfectant levels. Conclusions We investigated and mitigated a 2-phase clonal outbreak of M. abscessus linked to hospital tap water. Healthcare facilities with endemic NTM should consider similar tap water avoidance and engineering strategies to decrease risk of NTM infection.

Within the last decade, advancements in left ventricular assist device therapy have allowed patients with end-stage heart failure (HF) to live longer and with better quality of life. Like other life-saving interventions, however, there remains the risk of complications including infections, bleeding episodes, and stroke. The candidate for left ventricular assist device therapy faces complex challenges going forward, both physical and psychological, many of which may benefit from the application of palliative care principles by trained specialists. Despite these advantages, palliative care remains underused in many advanced HF programs. Here, we describe the benefits of palliative care, barriers to use within HF, and specific applications to the integrated care of patients on mechanical circulatory support.

Background Pre-transplant amiodarone use has been postulated as a risk factor for morbidity and mortality after orthotopic heart transplantation (OHT). We assessed pre-OHT amiodarone use and tested the hypothesis that it is associated with impaired post-OHT outcomes. Methods We performed a retrospective cohort analysis of adult OHT recipients from the registry of the International Society for Heart and Lung Transplantation (ISHLT). All patients had been transplanted between 2005 and 2013 and were stratified by pre-OHT amiodarone use. We derived propensity scores using logistic regression with amiodarone use as the dependent variable, and assessed the associations between amiodarone use and outcomes with Kaplan–Meier analysis after matching patients 1:1 based on propensity score, and with Cox regression with adjustment for propensity score. Results Of the 14,944 OHT patients in the study cohort, 32% ( N = 4,752) received pre-OHT amiodarone. Amiodarone use was higher in recent years (29% in 2005 to 2007, 32% in 2008 to 2010, 35% in 2011 to 2013). Amiodarone-treated patients were older and more frequently had a history of sudden cardiac death (27% vs 13%) and pre-OHT mechanical circulatory support. Key donor characteristics and allograft ischemia times were similar between groups. In propensity-matched analyses, amiodarone-treated patients had higher rates of cardiac reoperation (15% vs 13%) and permanent pacemaker (5% vs 3%) after OHT and before discharge. Amiodarone-treated patients also had higher 1-year mortality (hazard ratio 1.15, 95% confidence interval 1.02 to 1.30), but the risks of early graft failure, retransplantation and rehospitalization were similar between groups. Conclusions Amiodarone use before OHT was independently associated with increased 1-year mortality. The need for amiodarone therapy should be carefully and continuously assessed in patients awaiting OHT.

Atrial tissue gene expression profiling may help to determine how differentially expressed genes in the human atrium before cardiopulmonary bypass (CPB) are related to subsequent biologic pathway activation patterns, and whether specific expression profiles are associated with an increased risk for postoperative atrial fibrillation (AF) or altered response to β-blocker (BB) therapy after coronary artery bypass grafting (CABG) surgery. Right atrial appendage (RAA) samples were collected from 45 patients who were receiving perioperative BB treatment, and underwent CABG surgery. The isolated RNA samples were used for microarray gene expression analysis, to identify probes that were expressed differently in patients with and without postoperative AF. Gene expression analysis was performed to identify probes that were expressed differently in patients with and without postoperative AF. Gene set enrichment analysis (GSEA) was performed to determine how sets of genes might be systematically altered in patients with postoperative AF. Of the 45 patients studied, genomic DNA from 42 patients was used for target sequencing of 66 candidate genes potentially associated with AF, and 2,144 single-nucleotide polymorphisms (SNPs) were identified. We then performed expression quantitative trait loci (eQTL) analysis to determine the correlation between SNPs identified in the genotyped patients, and RAA expression. Probes that met a false discovery rate < 0.25 were selected for eQTL analysis. Of the 17,678 gene expression probes analyzed, 2 probes met our prespecified significance threshold of false discovery rate < 0.25. The most significant probe corresponded to vesicular overexpressed in cancer – prosurvival protein 1 gene (VOPP1; 1.83 fold change; P = 3.47 × 10−7), and was up-regulated in patients with postoperative AF, whereas the second most significant probe, which corresponded to the LOC389286 gene (0.49 fold change; P = 1.54 × 10−5), was down-regulated in patients with postoperative AF. GSEA highlighted the role of VOPP1 in pathways with biologic relevance to myocardial homeostasis, and oxidative stress and redox modulation. Candidate gene eQTL showed a trans-acting association between variants of G protein-coupled receptor kinase 5 gene, previously linked to altered BB response, and high expression of VOPP1. In patients undergoing CABG surgery, RAA gene expression profiling, and pathway and eQTL analysis suggested that VOPP1 plays a novel etiological role in postoperative AF despite perioperative BB therapy.

Improved quality of life for patients after left ventricular assist device (LVAD) implantation can be greatly limited by peripheral vascular disease even if heart failure symptoms are resolved by LVAD support. We present a case of concomitant thoracic aortobifemoral bypass and LVAD implantation in a patient with ischemic cardiomyopathy, severe peripheral vascular disease, and multiple previous failed revascularization attempts. In this patient, we used the LVAD outflow to provide the inflow to the femoral artery bypass graft. This graft has remained patent at a 2-year follow-up, without claudication symptoms. Performing concomitant major vascular operations safely and successfully is feasible in patients with LVADs. Quality of life after ventricular assist device placement can be limited by vascular disease, but it can be markedly improved after vascular surgical intervention.

Advances in technology for the delivery of venoarterial extracorporeal membrane oxygenation (VA-ECMO) have allowed for its expanded utilization in the treatment of patients with advanced cardiogenic shock, particularly through the use of peripheral cannulation strategies. However, peripheral VA-ECMO continues to be hampered by several major limitations including inadequate decompression of the left ventricle, lower limb ischemia, and the inability to mobilize patients. Here, we present a case series of three patients who were treated with a hybrid peripheral-central cannulation strategy accompanied by direct decompression of the left ventricle through a right anterior mini-thoracotomy. This novel approach ameliorates several of the current limitations to peripheral VA-ECMO therapy and thereby holds potential for improving outcomes in VA-ECMO patients.

The proportion of heart transplant recipients bridged with durable, intracorporeal left ventricular assist devices (dLVADs) has dramatically increased; however, concern exists regarding obligate repeat sternotomy, increased bleeding risk because of anticoagulation and acquired von Willebrand disease, and increased rates of allosensitization. Whether dLVAD patients have impaired posttransplant outcomes compared with equivalent patients with less invasive intraaortic balloon pump counterpulsation (IABP) at the time of transplant is unknown. Therefore, we analyzed adult, first time, heart-only transplant procedures with dLVAD (n = 2,636) compared with IABP (n = 571) at the time of transplant based on data from the United Network for Organ Sharing (UNOS) July 2004 to December 2011. There was clear geographic variation in IABP and dLVAD at transplant. Multivariable analysis demonstrated equivalent cumulative risk of death (adjusted Cox proportional hazard ratio, 1.08; 95% confidence interval, 0.87-1.33; p = 0.51). There was no significant difference in adjusted comparison of perioperative morality, length of stay, postoperative renal failure requiring dialysis, or early acute rejection (p ≥ 0.14 for all). Therefore, data from UNOS suggest that the presence of dLVAD at the time of heart transplantation does not have a detrimental effect on postoperative outcomes compared with IABP, which must be considered in the context of pretransplant mortality and locoregional organ availability.

Background In high-risk cardiac procedures, dynamic analysis of right ventricular (RV) performance is desirable, but the geometric complexity of the RV limits the applicability of current two-dimensional echocardiographic imaging techniques. This study aimed to evaluate the utility of three-dimensional transesophageal echocardiography (TEE) for the perioperative assessment of RV function and dimensions. Methods Patients undergoing cardiac surgical procedures with complete TEE examinations were identified and reviewed according to current guidelines to exclude patients with significant coexisting valvular regurgitation. Full-volume, three-dimensional datasets were analyzed by two independent investigators using stand-alone software, and left ventricular and RV dimensions were recorded. Results Datasets from 50 patients undergoing cardiac surgical procedures were evaluated for this study. The mean RV volume was 111.7 mL (range, 37.5 to 349.7 mL) at end diastole and 67.6 mL (range, 25.5 to 274.4 mL) at end systole. Intraobserver reliability was 0.93 and 0.90 for end diastolic and 0.77 and 0.87 for end systolic volumes. The interobserver reliability for RV volumes was 0.83 at end diastole and 0.86 at end systole. The mean stroke volume was 43.6 mL (range, 12 to 111.2 mL) for the RV and 49.1 mL (range, 19.9 to 102.8 mL) for the left ventricle; the correlation coefficient between the two was 0.85. Conclusions Three-dimensional TEE volumetric measurements were reproducible across a wide range of RV dimensions. As postulated by the continuity principle, stroke volume measurements between both ventricles correlated well, supporting the validity of this approach. Therefore, our work provides preliminary evidence that three-dimensional TEE offers reproducible information about RV function and size in the dynamic and complex perioperative setting of cardiac surgical procedures.

Purpose A universal loss of von Willebrand factor (vWF) high-molecular-weight multimers (HMWM) has been demonstrated in continuous-flow left ventricular assist device (HeartMate II) recipients. However, no reliable clinical or laboratory predictors for an increased bleeding tendency in this patient population have been identified. This study evaluated the ability of a new automated latex particle-enhanced immunoturbidimetric vWF activity assay (ALPEIVA) to predict non-surgical bleeding risk in HeartMate II recipients. Methods As part of a prospective multicenter trial, pre-surgical, 7-day, and 30-day post-implantation blood samples were collected from 24 patients. ALPEIVA-assessed vWF activities were compared among patients with and without non-surgical bleeding complications after HeartMate II implantation. Additional laboratory testing included factor VIII activity (FVIII:C), vWF antigen (vWFAg), vWF ristocetin cofactor activity (vWF:RCo), and vWF multimer analysis. Results All 24 patients had HMWM losses after HeartMate II implantation. Five patients (20%) developed non-surgical bleeding complications between 14 days and 6 months after HeartMate II implantation. Among various laboratory variables, only mean ALPEIVA/vWFAg ratios (referred to as the "bleeding ratio") were significantly lower in patients with clinically relevant bleeding (mean, 0.70 ± 0.06) compared with patients without bleeding (mean, 0.78 ± 0.09; p = 0.02) when measured at 30 days. Conclusions The post-surgical bleeding ratio could potentially predict non-surgical bleeding risk and guide anti-platelet and anti-coagulation strategies in HeartMate II recipients.

Successful amelioration of cardiac dysfunction and heart failure through gene therapy approaches will require a transgene effective at attenuating myocardial injury, and subsequent remodeling, using an efficient and safe delivery vehicle. Our laboratory has established a well-curated, high-quality repository of human myocardial tissues that we use as a discovery engine to identify putative therapeutic transgene targets, as well as to better understand the molecular basis of human heart failure. By using this rare resource we were able to examine age- and sex-matched left ventricular samples from (1) end-stage failing human hearts and (2) nonfailing human hearts and were able to identify the X-linked inhibitor of apoptosis protein (XIAP) as a novel target for treating cardiac dysfunction. We demonstrate that XIAP is diminished in failing human hearts, indicating that this potent inhibitor of apoptosis may be central in protecting the human heart from cellular injury culminating in heart failure. Efforts to ameliorate heart failure through delivery of XIAP compelled the design of a novel adeno-associated viral (AAV) vector, termed SASTG, that achieves highly efficient transduction in mouse heart and in cultured neonatal rat cardiomyocytes. Increased XIAP expression achieved with the SASTG vector inhibits caspase-3/7 activity in neonatal cardiomyocytes after induction of apoptosis through three common cardiac stresses: protein kinase C-γ inhibition, hypoxia, or β-adrenergic receptor agonist. These studies demonstrate the potential benefit of XIAP to correct heart failure after highly efficient delivery to the heart with the rationally designed SASTG AAV vector.

Transmission of pathogens from donor to recipient is a potential complication of organ transplantation. Herein, we describe the clinical course and outcomes of 4 transplant recipients who received tissues from a donor with multi-organ infection with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. Recipient 1 underwent simultaneous liver and kidney transplantation for alpha-1 antitrypsin deficiency and alcohol-related cirrhosis, and acute tubular necrosis, respectively. Soon after transplantation, he developed an infected hematoma and peritonitis due to KPC-producing K. pneumoniae despite receiving tigecycline prophylaxis. He was treated with a prolonged course of tigecycline, amikacin, and meropenem, in conjunction with surgical evacuation and percutaneous drainage of the infected fluid collections. Recipient 2 underwent living-donor liver transplantation for cholangiocarcinoma and primary sclerosing cholangitis using vein graft from the donor infected with KPC-producing K. pneumoniae. Culture of the preservation fluid containing the vein graft was positive for KPC-producing K. pneumoniae. The patient received preemptive amikacin and tigecycline, and he did not develop any infection (as evidenced by negative surveillance blood cultures). The isolates from the donor and Recipients 1 and 2 were indistinguishable by pulsed-field gel electrophoresis. Recipients 3 and 4 underwent kidney and heart transplantation, respectively; both patients received perioperative tigecycline prophylaxis and did not develop infections due to KPC-producing K. pneumoniae. All transplant recipients had good short-term outcomes. These cases highlight the importance of inter-institutional communication and collaboration to ensure the successful management of recipients of organs from donors infected with multidrug-resistant organisms.

In every common mitral pathology studied to date, repairing the patient's own diseased valve to adequate function has yielded superior long-term results as compared with prosthetic valve replacement with either tissue or mechanical devices. Thus, increasing rates of mitral repair across all valve pathologies would seem to be a logical clinical goal. Techniques for mitral valve repair have undergone continual evolution over the past 50 years. Recently, emphasis has been placed on preserving leaflet surface area and avoiding tissue resection, by combining the methods of Gore-Tex artificial chordal replacement, autologous pericardial leaflet augmentation, and full ring annuloplasty. Using combinations of these three techniques appropriate to the given valve pathology, acute mitral repair rates now are approximating 98% for all common mitral disease etiologies. Simultaneously, operative mortalities for mitral repair have fallen significantly and now are negligible, whereas long-term outcomes using these methods have been increasingly more stable. As a result of innovations from multiple sources, mitral valve surgery has been converted from a higher risk procedure to one of the safest operations in most centers. This review will detail the technical application of “nonresectional” mitral repair approaches to a broad range of mitral disease pathologies.

Caregivers for patients undergoing solid organ transplantation play an essential role in the process of transplantation. However, little is known about stress and coping among these caregivers. Six hundred and twenty-one primary caregivers of potential candidates for lung (n = 317), liver (n = 147), heart (n = 115), and/or kidney (n = 42) transplantation completed a psychometric test battery at the time of the candidate's initial pre-transplant psychosocial evaluation. Caregivers were generally well adjusted, with only 17% exhibiting clinical symptoms of depression (Beck Depression Inventory-II score >13) and 13% reporting clinical levels of anxiety (State Trait Anxiety Inventory score >48). Greater caregiver burden and negative coping styles were associated with higher levels of depression. Greater objective burden and avoidant coping were associated with higher levels of anxiety. Caregivers evidenced a high degree of socially desirable (i.e., defensive) responding, which may reflect a deliberate effort to minimize fears or worries so as to not jeopardize patients' listing status.

Implantable and extracorporeal cardiovascular devices are commonly made from titanium (Ti) (e.g. Ti-coated Nitinol stents and mechanical circulatory assist devices). Endothelializing the blood-contacting Ti surfaces of these devices would provide them with an antithrombogenic coating that mimics the native lining of blood vessels and the heart. We evaluated the viability and adherence of peripheral blood-derived porcine endothelial progenitor cells (EPCs), seeded onto thin Ti layers on glass slides under static conditions and after exposure to fluid shear stresses. EPCs attached and grew to confluence on Ti in serum-free medium, without preadsorption of proteins. After attachment to Ti for 15 min, less than 5% of the cells detached at a shear stress of 100 dyne / cm2. Confluent monolayers of EPCs on smooth Ti surfaces (Rq of 10 nm), exposed to 15 or 100 dyne / cm2 for 48 h, aligned and elongated in the direction of flow and produced nitric oxide dependent on the level of shear stress. EPC-coated Ti surfaces had dramatically reduced platelet adhesion when compared to uncoated Ti surfaces. These results indicate that peripheral blood-derived EPCs adhere and function normally on Ti surfaces. Therefore EPCs may be used to seed cardiovascular devices prior to implantation to ameliorate platelet activation and thrombus formation.

A 62-year-old woman with a history of lung cancer, prior surgical aortic valve replacement with a 23-mm Hancock (Medtronic, Inc, Minneapolis, MN) porcine valve, and nonischemic cardiomyopathy supported with a HeartMate II destination therapy left ventricular assist device (LVAD; Thoratec Corporation, Pleasanton, CA) presented with hemolytic anemia (hemoglobin, 6.8 g/dL; lactate dehydrogenase, 1536 U/L) because of LVAD thrombosis and severe insufficiency of the 23-mm Hancock bioprosthetic valve (Figure 1; Movie I in the Data Supplement). Given her comorbidities and multiple prior sternotomies, she was felt to be a poor candidate for combined redo-surgical aortic valve and LVAD replacement via another sternotomy. Peripheral vascular disease precluded transfemoral transcatheter aortic valve replacement (TAVR). Therefore, it was decided that she would be best treated with concomitant LVAD pump exchange and TAVR via a transapical approach using the existing LVAD inflow cannula for access. Figure 1. Intraoperative aortogram showing severe bioprosthetic aortic valve insufficiency. Note the Coda occlusion balloon in the left ventricular assist device (LVAD) outflow cannula (*), LVAD inflow cannula (**) through which the Amplatz Extra Stiff wire can be seen traversing the porcine aortic valve, percutaneous venous cardiopulmonary bypass cannula (arrow), and temporary transvenous pacemaker in the right ventricle (arrowhead). A 5-cm incision was made below the lateral two thirds of the right clavicle to access the right axillary artery, and a 6-mm Dacron …

A 60-year-old man with end-stage heart failure underwent orthotopic heart transplantation. Before transplantation, he had elevated pulmonary artery (PA) pressures (60/17 mm Hg, mean PA 35 mm Hg) and pulmonary vascular resistance (PVR) (6.6 Wood units). Following transplantation, he initially did

Previous studies suggest that mitral valve replacement is comparable to repair in the elderly, and a national trend exists toward tissue valves. However, few direct comparison data are available, and this study evaluated the effects of patient age on risk-adjusted survival after mitral procedures.From 1986 to 2006, 2,064 patients underwent isolated primary mitral operations (±CABG). Maximal follow-up was 20 years with a median of 5 years. Valve disease etiology was the following: degenerative, 864; ischemic, 450; rheumatic, 416; endocarditis, 98; and "other," 236. Overall, 58% had repair and 39% had concomitant coronary artery bypass grafting. Survival differences were evaluated with a Cox proportional hazards model that included baseline characteristics, valve disease etiology, and choice of repair versus replacement with tissue or mechanical valves.Baseline risk profiles generally were better for mechanical valves, and age was the most significant multivariable predictor of late mortality [hazard ratio = 1.4 per 10-year increment, Wald χ(2) = 32.7, p0.0001]. As compared with repair, risk-adjusted survival was inferior with either tissue valves [1.8, 27.6,0.0001] or mechanical valves [1.3, 8.1, 0.0044], and no treatment interaction was observed with age (p = 0.18). At no patient age did tissue valves achieve equivalent survival to either repair or mechanical valves.Mitral repair is associated with better survival than valve replacement across the spectrum of patient age. If replacement is required, mechanical valves achieve better outcomes, even in the elderly. These data suggest that tissue valves should be reserved only for patients with absolute contraindications to anticoagulation who are not amenable to repair.

BACKGROUND: The relationship between duration of platelet (PLT) storage, currently limited to 5 days, and surgical outcomes has not been established. We tested the hypothesis that PLT storage age was associated with adverse outcomes. STUDY DESIGN AND METHODS: A retrospective cohort of aortocoronary bypass (CABG) surgery patients from January 1996 to January 2005 receiving one or more PLT transfusions was selected for study. The composite primary (“short-term”) outcome was 30-day mortality or prolonged hospital stay. Secondary outcomes included complications and survival to annual follow-up. Multivariable logistic regression models and Cox proportional hazards regression analysis evaluated the association between PLT storage age and outcomes, expressed as an odds ratio (OR) or hazard ratio with 95% confidence intervals (CIs), respectively. RESULTS: PLT transfusion was administered to 3272 of 10,275 CABG patients and 2578 received units of known storage age, which ranged between 2 and 5 days (median, 4 days; 25th percentile, 3 days; 75th percentile, 5 days). The mortality rate for the 1637 patients receiving a single plateletpheresis transfusion was 3.8%, while 21.6% experienced a prolonged hospital stay or death. After adjusting for the number of PLT and red blood cell (RBC) units transfused, RBC storage age, and preoperative mortality risk, there was no association between PLT storage age and short-term outcome (OR, 1.01; 95% CI, 0.90-1.14), survival (hazard ratio [HR], 1.04; 95% CI, 0.96-1.13), or postoperative infections. CONCLUSIONS: PLT storage age was not associated with adverse short-term outcomes, decreased long-term survival, or infections after cardiac surgery.

Invasive mold disease in thoracic organ transplant recipients is a well-recognized complication, but the long-term persistence of molds within the human body and evasion of host defenses has not been well-described. We present two cases of invasive mold disease (Verruconis gallopava and Aspergillus fumigatus) in thoracic transplant recipients who had the same mold cultured years prior to the invasive disease presentation. The paired isolates from the index and recurrent infections in both patients were compared using whole genome sequencing to determine if the same strain of mold caused both the index and recurrent infections. In Case 1, the isolates were found to be of the same strain indicating that the initial colonizing isolate identified pre-transplant eventually caused invasive mold disease post-transplant while in Case 2, the two isolates were not of the same strain. These results demonstrate the distinct possibility of molds both persisting within the human body for years prior to invasive mold disease or the long-term risk of recurrent, persistent infection with more than one strain. Further studies of long-term molecular epidemiology of IMD and risk factors for mold persistence in transplant recipients are encouraged.