Metabolomic profiling during ex situ normothermic perfusion before heart transplantation defines patterns of substrate utilization and correlates with markers of allograft injury.

BACKGROUND: Cardiac metabolism is altered in heart failure and ischemia-reperfusion injury states. We hypothesized that metabolomic profiling during ex situ normothermic perfusion before heart transplantation (HT) would lend insight into myocardial substrate utilization and report on subclinical and clinical allograft dysfunction risk. METHODS: Metabolomic profiling was performed on serial samples of ex situ normothermic perfusate assaying biomarkers of myocardial injury in lactate and cardiac troponin I (TnI) as well as metabolites (66 acylcarnitines, 15 amino acids, nonesterified fatty acids [NEFA], ketones, and 3-hydroxybutyrate). We tested for change over time in injury biomarkers and metabolites, along with differential changes by recovery strategy (donation after circulatory death [DCD] vs donation after brain death [DBD]). We examined associations between metabolites, injury biomarkers, and primary graft dysfunction (PGD). Analyses were performed using linear mixed models adjusted for recovery strategy, assay batch, donor-predicted heart mass, and time. RESULTS: A total of 176 samples from 92 ex situ perfusion runs were taken from donors with a mean age of 35 (standard deviation 11.3) years and a median total ex situ perfusion time of 234 (interquartile range 84) minutes. Lactate trends over time differed significantly by recovery strategy, while TnI increased during ex situ perfusion regardless of DCD vs DBD status. We found fuel substrates were rapidly depleted during ex situ perfusion, most notably the branched-chain amino acids leucine/isoleucine, as well as ketones, 3-hydroxybutyrate, and NEFA (least squares [LS] mean difference from the first to last time point -1.7 to -4.5, false discovery rate q < 0.001). Several long-chain acylcarnitines (LCAC), including C16, C18, C18:1, C18:2, C18:3, C20:3, and C20:4, increased during the perfusion run (LS mean difference 0.42-0.67, q < 0.001). Many LCACs were strongly associated with lactate and TnI. The change over time of many LCACs was significantly different for DCD vs DBD, suggesting differential trends in fuel substrate utilization by ischemic injury pattern. Changes in leucine/isoleucine, arginine, C12:1-OH/C10:1-DC, and C16-OH/C14-DC were associated with increased odds of moderate-severe PGD. Neither end-of-run nor change in lactate or TnI was associated with PGD. CONCLUSIONS: Metabolomic profiling of ex situ normothermic perfusion solution reveals a pattern of fuel substrate utilization that correlates with subclinical and clinical allograft dysfunction. This study highlights a potential role for interventions focused on fuel substrate modification in allograft conditioning during ex situ perfusion to improve allograft outcomes.

Inhaled Epoprostenol Compared With Nitric Oxide for Right Ventricular Support After Major Cardiac Surgery.

BACKGROUND: Right ventricular failure (RVF) is a leading driver of morbidity and death after major cardiac surgery for advanced heart failure, including orthotopic heart transplantation and left ventricular assist device implantation. Inhaled pulmonary-selective vasodilators, such as inhaled epoprostenol (iEPO) and nitric oxide (iNO), are essential therapeutics for the prevention and medical management of postoperative RVF. However, there is limited evidence from clinical trials to guide agent selection despite the significant cost considerations of iNO therapy. METHODS: In this double-blind trial, participants were stratified by assigned surgery and key preoperative prognostic features, then randomized to continuously receive either iEPO or iNO beginning at the time of separation from cardiopulmonary bypass with the continuation of treatment into the intensive care unit stay. The primary outcome was the composite RVF rate after both operations, defined after transplantation by the initiation of mechanical circulatory support for isolated RVF, and defined after left ventricular assist device implantation by moderate or severe right heart failure according to criteria from the Interagency Registry for Mechanically Assisted Circulatory Support. An equivalence margin of 15 percentage points was prespecified for between-group RVF risk difference. Secondary postoperative outcomes were assessed for treatment differences and included: mechanical ventilation duration; hospital and intensive care unit length of stay during the index hospitalization; acute kidney injury development including renal replacement therapy initiation; and death at 30 days, 90 days, and 1 year after surgery. RESULTS: Of 231 randomized participants who met eligibility at the time of surgery, 120 received iEPO, and 111 received iNO. Primary outcome occurred in 30 participants (25.0%) in the iEPO group and 25 participants (22.5%) in the iNO group, for a risk difference of 2.5 percentage points (two one-sided test 90% CI, -6.6% to 11.6%) in support of equivalence. There were no significant between-group differences for any of the measured postoperative secondary outcomes. CONCLUSIONS: Among patients undergoing major cardiac surgery for advanced heart failure, inhaled pulmonary-selective vasodilator treatment using iEPO was associated with similar risks for RVF development and development of other postoperative secondary outcomes compared with treatment using iNO. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03081052.

Epidemiology, management, and clinical outcomes of extrapulmonary Mycobacterium abscessus complex infections in heart transplant and ventricular assist device recipients.

Nontuberculous mycobacteria are emerging pathogens, yet data on the epidemiology and management of extrapulmonary nontuberculous mycobacteria infections in orthotopic heart transplantation (OHT) and ventricular assist device (VAD) recipients are scarce. We retrospectively reviewed records of OHT and VAD recipients who underwent cardiac surgery at our hospital and developed Mycobacterium abscessus complex (MABC) infection from 2013 to 2016 during a hospital outbreak of MABC linked to heater-cooler units. We analyzed patient characteristics, medical and surgical management, and long-term outcomes. Ten OHT patients and 7 patients with VAD developed extrapulmonary M. abscessus subspecies abscessus infection. The median time from presumed inoculation during cardiac surgery to the first positive culture was 106 days in OHT and 29 days in VAD recipients. The most common sites of positive cultures were blood (n = 12), sternum/mediastinum (n = 8), and the VAD driveline exit site (n = 7). The 14 patients diagnosed when alive received combination antimicrobial therapy for a median of 21 weeks, developed 28 antibiotic-related adverse events, and underwent 27 surgeries. Only 8 (47%) patients survived longer than 12 weeks after diagnosis, including 2 patients with VAD who experienced long-term survival after an explantation of infected VADs and OHT. Despite aggressive medical and surgical management, OHT and VAD patients with MABC infection experienced substantial morbidity and mortality.

The impact of race on utilization of durable left ventricular assist device therapy in patients with advanced heart failure.

BACKGROUND: Heart failure affects >6 million people in the United States alone and is most prevalent in Black patients who suffer the highest mortality risk. Yet prior studies have suggested that Black patients are less likely to receive advanced heart failure therapy. We hypothesized that Black patients would have decreased rates of durable left ventricular assist device (LVAD) implantation within our expansive heart failure program. METHODS: A retrospective single-center cohort study was conducted at a single high-volume academic medical center. Patients between 18 and 85 years admitted with a diagnosis of cardiogenic shock or congestive heart failure between 1, 2013 and 12, 2017 with a left ventricular ejection fraction < 30% and inotropic dependence or need for mechanical circulatory support were included. Patients with contraindications to durable LVAD were excluded. An adjusted logistic regression model for durable LVAD implantation within 90 days of the index admission was used to determine the effect of race on durable LVAD implantation. RESULTS: Among the 702 study patients (60.9% White, 34.1% Black), durable LVAD implantation was performed within 90 days of the index admission in 183 (26%) of the cohort. After multivariate analysis, Black patients were not found to have a statistically significant difference in durable LVAD implantation rates compared to White patients in our study (OR: 0.68 [95% confidence interval: 0.45-1.04; p: .074]). CONCLUSIONS: Black patients in our study did not have a statistically significant difference in the rate of durable LVAD implantation compared with White patients after adjustments were made for age, sex, socioeconomic, and clinical covariates. Larger prospective studies are needed to validate these findings.

Polypharmacy in Palliative Care for Advanced Heart Failure: The PAL-HF Experience.

BACKGROUND: Palliative care (PC) in advanced heart failure (HF) aims to improve symptoms and quality of life (QOL), in part through medication management. The impact of PC on polypharmacy (>5 medications) remains unknown. METHODS AND RESULTS: We explored patterns of polypharmacy in the Palliative Care in HF (PAL-HF) randomized controlled trial of standard care vs interdisciplinary PC in advanced HF (N = 150). We describe differences in medication counts between arms at 2, 6, 12, and 24 weeks for HF (12 classes) and PC (6 classes) medications. General linear mixed models were used to evaluate associations between treatment arm and polypharmacy over time. The median age of the patients was 72 years (interquartile range 62-80 years), 47% were female, and 41% were Black. Overall, 48% had ischemic etiology, and 55% had an ejection fraction of 40% or less. Polypharmacy was present at baseline in 100% of patients. HF and PC medication counts increased in both arms, with no significant differences in counts by drug class at any time point between arms. CONCLUSIONS: In a trial of patients with advanced HF considered eligible for PC, polypharmacy was universal at baseline and increased during follow-up with no effect of the palliative intervention on medication counts relative to standard care.

Surgical Treatment of Tricuspid Valve Regurgitation in Patients Undergoing Left Ventricular Assist Device Implantation: Interim analysis of the TVVAD trial.

OBJECTIVES: Right heart failure remains a serious complication of left ventricular assist device therapy. Many patients presenting for left ventricular assist device implantation have significant tricuspid regurgitation. It remains unknown whether concurrent tricuspid valve surgery reduces postoperative right heart failure. The primary aim was to identify whether concurrent tricuspid valve surgery reduced the incidence of moderate or severe right heart failure within the first 6 months after left ventricular assist device implantation. METHODS: Patients with moderate or severe tricuspid regurgitation on preoperative echocardiography were randomized to left ventricular assist device implantation alone (no tricuspid valve surgery) or with concurrent tricuspid valve surgery. Randomization was stratified by preoperative right ventricular dysfunction. The primary end point was the frequency of moderate or severe right heart failure within 6 months after surgery. RESULTS: This report describes a planned interim analysis of the first 60 randomized patients. The tricuspid valve surgery group (n = 32) had mild or no tricuspid regurgitation more frequently on follow-up echocardiography studies compared with the no tricuspid valve surgery group (n = 28). However, at 6 months, the incidence of moderate and severe right heart failure was similar in each group (tricuspid valve surgery: 46.9% vs no tricuspid valve surgery: 50%, P = .81). There was no significant difference in postoperative mortality or requirement for right ventricular assist device between the groups. There were also no significant differences in secondary end points of functional status and adverse events. CONCLUSIONS: The presence of significant tricuspid regurgitation before left ventricular assist device is associated with a high incidence of right heart failure within the first 6 months after surgery. Tricuspid valve surgery was successful in reducing postimplant tricuspid regurgitation compared with no tricuspid valve surgery but was not associated with a lower incidence of right heart failure.

Pericardial Adipose Tissue Volume and Left Ventricular Assist Device-Associated Outcomes.

BACKGROUND: Pericardial adipose tissue (PAT) is associated with adverse cardiovascular outcomes in those with and without established heart failure (HF). However, it is not known whether PAT is associated with adverse outcomes in patients with end-stage HF undergoing left ventricular assist device (LVAD) implantation. This study aimed to evaluate the associations between PAT and LVAD-associated outcomes. METHODS AND RESULTS: We retrospectively measured computed tomography-derived PAT volumes in 77 consecutive adults who had available chest CT imaging prior to HeartMate 3 LVAD surgery between October 2015 and March 2019 at Duke University Hospital. Study groups were divided into above-median (≥219 cm3) and below-median (<219 cm3) PAT volume. Those with above-median PAT had a higher proportion of atrial fibrillation, chronic kidney disease and ischemic cardiomyopathy. Groups with above-median vs below-median PAT had similar Kaplan-Meier incidence rates over 2 years for (1) composite all-cause mortality, redo-LVAD surgery and cardiac transplantation (35.9 vs 32.2%; log-rank P = 0.65) and (2) composite incident hospitalizations for HF, gastrointestinal bleeding, LVAD-related infection, and stroke (61.5 vs 60.5%; log-rank P = 0.67). CONCLUSIONS: In patients with end-stage HF undergoing LVAD therapy, PAT is not associated with worse 2-year LVAD-related outcomes. The significance of regional adiposity vs obesity in LVAD patients warrants further investigation.

Electrical storm in patients with left ventricular assist devices: Risk factors, incidence, and impact on survival.

BACKGROUND: Ventricular arrhythmias (VAs) and electrical storm (ES) are recognized complications following left ventricular assist device (LVAD) implantation; however, their association with long term-outcomes remains poorly understood. OBJECTIVE: The purpose of this study was to describe the clinical impact of ES in a population of patients undergoing LVAD implantation at a quaternary care center in the United States. METHODS: This was an observational retrospective study of patients undergoing LVAD implantation from 2009 to 2020 at Duke University Hospital. The incidence of ES (≥3 sustained VA episodes over a 24-hour period without an identifiable reversible cause) was determined from patient records. Risk factors for ES were identified using multivariable Cox proportional hazards modeling. RESULTS: Among 730 patients undergoing LVAD implant, 78 (10.7%) developed ES at a median of 269 (interquartile range [IQR] 7-766) days following surgery. Twenty-seven patients (34.6%) developed ES within 30 days, while 51 (65.4%) presented with ES at a median 639 (IQR 281-1017) days after implant. Following ES, 41% of patients died within 1 year. Patients who developed ES were more likely to have a history of VAs, ventricular tachycardia ablation, antiarrhythmic drug use, and perioperative mechanical circulatory support around the time of LVAD implant than patients without ES. CONCLUSION: ES occurs in 1 in 10 patients after LVAD and is associated with higher mortality. Risk factors for ES include a history of VAs, VT ablation, antiarrhythmic drug use, and perioperative mechanical circulatory support. Optimal management of ES surrounding LVAD implant, including escalation of medical therapy, catheter ablation, or adjunctive sympatholytic therapies, remains uncertain.

Splanchnic Nerve Block Mediated Changes in Stressed Blood Volume in Heart Failure.

OBJECTIVES: The authors estimated changes of stressed blood volume (SBV) induced by splanchnic nerve block (SNB) in patients with either decompensated or ambulatory heart failure with reduced ejection fraction (HFrEF). BACKGROUND: The splanchnic vascular capacity is a major determinant of the SBV, which in turn determines cardiac filling pressures and may be modifiable through SNB. METHODS: We analyzed data from 2 prospective, single-arm clinical studies in decompensated HFrEF (splanchnic HF-1; resting hemodynamics) and ambulatory heart failure (splanchnic HF-2; exercise hemodynamics). Patients underwent invasive hemodynamics and short-term SNB with local anesthetics. SBV was simulated using heart rate, cardiac output, central venous pressure, pulmonary capillary wedge pressure, systolic and diastolic systemic arterial and pulmonary artery pressures, and left ventricular ejection fraction. SBV is presented as ml/70 kg body weight. RESULTS: Mean left ventricular ejection fraction was 21 ± 11%. In patients with decompensated HFrEF (n = 11), the mean estimated SBV was 3,073 ± 251 ml/70 kg. At 30 min post-SNB, the estimated SBV decreased by 10% to 2,754 ± 386 ml/70 kg (p = 0.003). In ambulatory HFrEF (n = 14) patients, the mean estimated SBV was 2,664 ± 488 ml/70 kg and increased to 3,243 ± 444 ml/70 kg (p < 0.001) at peak exercise. The resting estimated SBV was lower in ambulatory patients with HFrEF than in decompensated HFrEF (p = 0.019). In ambulatory patients with HFrEF, post-SNB, the resting estimated SBV decreased by 532 ± 264 ml/70 kg (p < 0.001). Post-SNB, with exercise, there was no decrease of estimated SBV out of proportion to baseline effects (p = 0.661). CONCLUSIONS: The estimated SBV is higher in decompensated than in ambulatory heart failure. SNB reduced the estimated SBV in decompensated and ambulatory heart failure. The reduction in estimated SBV was maintained throughout exercise. (Splanchnic Nerve Anesthesia in Heart Failure, NCT02669407; Abdominal Nerve Blockade in Chronic Heart Failure, NCT03453151).

Mitigating the Impact of Using Female Donor Hearts in Male Recipients Using BMI Difference.

BACKGROUND: Heart transplantation is limited by the supply of donor organs. Previous studies have associated female donor to male recipient with decreased posttransplant survival. We wanted to evaluate whether this risk can be mitigated using higher donor than recipient body mass index (BMI). METHODS: We performed a retrospective analysis of the Organ Procurement and Transplantation Network/United Network of Organ Sharing registry encompassing years 2005 to 2018 for all male adult recipients (>18 years of age) who underwent isolated heart transplantation with grafts from female donors. The association between donor and recipient BMI difference and recipient survival was evaluated using adjusted Cox proportional hazards modeling. RESULTS: A total of 3788 male recipients who received female donor hearts met inclusion criteria for analysis. Maximally selected rank statistics identified donor minus recipient BMI of 1.5 kg/m2 as a meaningful cutoff point in the analysis of recipient survival. Multivariable Cox proportional hazards analysis demonstrated that increasing donor BMI relative to recipient BMI up to this cutoff point was associated with improved survival (hazard ratio per 5-unit difference, 0.87; 95% confidence interval, 0.77-0.99). Above this cutoff point, increasing donor BMI relative to the recipient did not improve survival more than what was achieved by adding 1.5 of BMI difference (hazard ratio per 5-unit difference, 0.97; 95% confidence interval, 0.90-1.04). CONCLUSIONS: Increasing donor BMI relative to recipient BMI up to 1.5 kg/m2 greater than recipient BMI was associated with improved survival. BMI difference may be useful as a simple surrogate for predicted heart mass difference to help mitigate the impact of sex mismatch in heart transplantation.

Cardiovascular Implantable Electronic Device Surgery Following Left Ventricular Assist Device Implantation.

OBJECTIVES: This study sought to determine the indications, characteristics, and outcomes of cardiovascular implantable electronic device (CIED) surgery in patients with LVAD. BACKGROUND: Many patients with a left ventricular assist device (LVAD) will require implantable cardioverter-defibrillator generator change or device revision or are candidates for de novo implantable cardioverter-defibrillator implantation following LVAD implantation. METHODS: We performed an observational retrospective study of all LVAD recipients who subsequently underwent CIED surgery at Duke University Hospital from 2009 to 2019. RESULTS: A total of 159 patients underwent CIED surgery following LVAD implantation, including generator change (n = 93), device revision (n = 38), and de novo implant (n = 28). The median (interquartile range) time from LVAD implantation to CIED surgery was 18.1 months (5.5 to 35.1 months). Pre-operative risk for infection was elevated in the overall cohort with a median (interquartile range) Prevention of Arrhythmia Device Infection Trial (PADIT) score of 7.0 (5.0 to 9.0). Pocket hematoma occurred in 21 patients (13.2%) following CIED surgery. Antimicrobial envelops were used in 43 patients (27%). Device infection due to CIED surgery occurred in 5 (3.1%) patients and occurred only in patients who developed post-operative pocket hematoma (p < 0.001). Mortality at 1 year following CIED surgery was 20% (n = 32). CONCLUSIONS: CIED surgery following LVAD implantation is associated with an increased risk for pocket hematoma and CIED infection. Further studies are needed to determine the risk-benefit ratio of CIED surgery in patients with LVADs.

Splanchnic Nerve Block for Chronic Heart Failure.

OBJECTIVES: We hypothesized that splanchnic nerve blockade (SNB) would attenuate increased exercise-induced cardiac filling pressures in patients with chronic HF. BACKGROUND: Chronic heart failure (HF) is characterized by limited exercise capacity driven in part by an excessive elevation of cardiac filling pressures. METHODS: This is a prospective, open-label, single-arm interventional study in chronic HF patients. Eligible patients had a wedge pressure ≥15 mm Hg at rest or ≥25 mm Hg with exercise on baseline right heart catheterization. Patients underwent cardiopulmonary exercise testing with invasive hemodynamic assessment, followed by percutaneous SNB with ropivacaine. RESULTS: Nineteen patients were enrolled, 15 of whom underwent SNB. The average age was 58 ± 13 years, 7 (47%) patients were women and 6 (40%) were black. Left ventricular ejection fraction was ≤35% in 14 (93%) patients. No procedural complications were encountered. SNB reduced mean pulmonary arterial pressure at peak exercise from 54.1 ± 14.4 (pre-SNB) to 45.8 ± 17.7 mm Hg (p < 0.001) (post-SNB). Similarly, SNB reduced exercise-induced wedge pressure from 34.8 ± 10.0 (pre-SNB) to 25.1 ± 10.7 mm Hg (p < 0.001) (post-SNB). The cardiac index changed with peak exercise from 3.4 ± 1.2 (pre-SNB) to 3.8 ± 1.1 l/min/m2 (p = 0.011) (post-SNB). After SNB, patients exercised for approximately the same duration at a greater workload (33 ± 24 W vs. 50 ± 30 W; p = 0.019) and peak oxygen consumption VO2 (9.1 ± 2.5 vs. 9.8 ± 2.7 ml/kg/min; p = 0.053). CONCLUSIONS: SNB reduced resting and exercise-induced pulmonary arterial and wedge pressure with favorable effects on cardiac output and exercise capacity. Continued efforts to investigate short- and long-term effects of SNB in chronic HF are warranted. Clinical Trials Registration (Abdominal Nerve Blockade in Chronic Heart Failure; NCT03453151).

Sex Differences in Quality of Life and Clinical Outcomes in Patients With Advanced Heart Failure: Insights From the PAL-HF Trial.

BACKGROUND: Palliative care improves quality of life in patients with heart failure. Whether men and women with heart failure derive similar benefit from palliative care interventions remains unknown. METHODS: In a secondary analysis of the PAL-HF trial (Palliative Care in Heart Failure), we analyzed differences in quality of life among men and women with heart failure and assessed for differential effects of the palliative care intervention by sex. Differences in clinical characteristics and quality-of-life metrics were compared between men and women at serial time points. The primary outcome was change in Kansas City Cardiomyopathy Questionnaire score between baseline and 24 weeks. RESULTS: Among the 71 women and 79 men, there was a significant difference in baseline Kansas City Cardiomyopathy Questionnaire (24.5 versus 36.2, respectively; P=0.04) but not Functional Assessment of Chronic Illness Therapy-Palliative Care scale (115.7 versus 120.3; P=0.27) scores. Among those who received the palliative care intervention (33 women and 42 men), women's quality-of-life score remained lower than that of men after enrollment. Treated men's scores were significantly higher than those untreated (6-month Kansas City Cardiomyopathy Questionnaire, 68.0 [interquartile range, 52.6-85.7] versus 41.1[interquartile range, 32.0-78.3]; P=0.047), whereas the difference between treated and untreated women was not significantly different (P=0.39). Rates of death and rehospitalization, as well as the composite end point, were similar between treated and untreated women and men. CONCLUSIONS: In the PAL-HF trial, women with heart failure experienced a greater symptom burden and poorer quality of life as compared with men. The change in treated men's Kansas City Cardiomyopathy Questionnaire score between baseline and 24 weeks was significantly higher than those untreated; this trend was not observed in women. Thus, there may be a sex disparity in response to palliative care intervention, suggesting that sex-specific approaches to palliative care may be needed to improve outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT0158960.

Left ventricular assist systems and infection-related outcomes: A comprehensive analysis of the MOMENTUM 3 trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Renal Outcomes in Patients Bridged to Heart Transplant With a Left Ventricular Assist Device.

BACKGROUND: Patients with end-stage heart failure are increasingly being bridged to heart transplant (BTT) with mechanical circulatory support; however the association between a left ventricular assist device (LVAD) BTT strategy and posttransplant renal outcomes is unclear. The aim of this study was to analyze the association of LVAD BTT with the development of posttransplant renal failure using a large national registry. METHODS: We queried the 2009 to 2018 United Network for Organ Sharing registry for all adults undergoing first-time heart or heart-kidney transplantation and stratified patients by use of pretransplant durable LVAD. The primary outcome of interest was posttransplant renal failure, which was evaluated with multivariable logistic regression. RESULTS: Of 18,307 patients meeting inclusion criteria, 7887 were (43%) and 10,420 were not (57%) BTT with an LVAD. BTT patients had slightly better baseline renal function (estimated glomerular filtration rate, 68.7 vs 65.8 mL/min, P < .001) and were less likely to receive a heart-kidney transplant (2.7% vs 4.8%, P < .001). On multivariable logistic regression, LVAD BTT strategy was not independently associated with posttransplant renal failure (odds ratio, 1.13; 95% confidence interval, 0.86-1.49). Similarly LVAD BTT among patients with preoperative renal dysfunction was not associated with posttransplant renal failure (adjusted odds ratio, 1.40; 95% confidence interval, 0.91-2.18). CONCLUSIONS: BTT with an LVAD does not appear to be associated with worse renal outcomes regardless of baseline renal function. Furthermore, an LVAD BTT strategy in patients with chronic kidney disease may enable clinicians to identify candidates suitable for isolated heart transplantation without increasing their risk for posttransplant renal failure.

Early outcomes with durable left ventricular assist device replacement using the HeartMate 3.

BACKGROUND: The HeartMate 3 (HM3) left ventricular assist device (LVAD) (Abbott, Inc, Chicago, Ill) is a fully magnetically levitated centrifugal implantable pump used to treat patients with chronic heart failure. The MOMENTUM (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) trial demonstrated that patients treated with the HM3 experienced reduced need for reoperation for LVAD replacement compared with a control group receiving an axial flow design, Heartmate II (Abbott, Inc). However, there are few reports of using HM3 as the replacement pump in patients who already are supported by a durable LVAD and experience a device-related complication necessitating replacement. METHODS: An institutional LVAD database was used to identify 19 consecutive patients who underwent pump replacement to HM3 (group 1) versus 85 consecutive control patients who underwent pump replacement to either Heartmate II or HeartWare Ventricular Assist Device (Medtronic Inc, Minneapolis, Minn) (group 2), at a single institution from January 2010 to August 2018. Patient baseline characteristic and outcomes were obtained from a prospectively maintained database. The primary endpoint was a composite of freedom from death or need for another replacement surgery. RESULTS: There was no difference between the groups in heart failure etiology, indication for replacement, as well as the average days on the previous pump or the type of previous pump. The HM3 group did have a significantly greater body mass index (37 vs 31.6 P = .01), a greater number of previous LVAD implants (36.8% vs 5.9%, had 2 previous LVADs, P < .001), and a greater number of previous sternotomies (31.6% vs 7.1%, had 3 previous sternotomies, P = .001). No difference was found between the groups in terms of postoperative adverse event rates. With regards to the primary endpoint, the patients with HM3 replacements (group 1) versus group 2 experienced significantly greater freedom from either death or need for another replacement during the follow-up period (P = .039). During follow-up, there were no thrombosis events for the patients who received replacement with HM3. CONCLUSIONS: LVAD replacement with HM3 can be performed safely and may be considered as the pump of choice in patients requiring LVAD replacement.

Influence of donor brain death duration on outcomes following heart transplantation: A United Network for Organ Sharing Registry analysis.

OBJECTIVES: We hypothesized that an increased duration of donor brain death may worsen survival following orthotopic heart transplantation. METHODS: The United Network for Organ Sharing Registry was queried for first-time, adult recipients of heart transplant from 2006 to 2018. Cox proportional hazards with penalized smooth splines was used to stratify patients based on donor brain death interval: shorter (<22 hours), reference (22-42 hours), and longer (>42 hours). Overall survival was estimated using Kaplan-Meier and Cox proportional hazards models. RESULTS: A total of 22,960 patients met study criteria (9.2% shorter, 55.0% reference, and 35.8% longer). Longer brain death duration recipients were more likely to have a later year of transplant and have a mechanical bridge to transplant, whereas longer duration donors were more likely to be black and die of anoxia compared with shorter duration and reference donors. Compared with reference, neither shorter (hazard ratio, 1.02; 95% confidence interval, 0.94-1.12) nor longer donor brain death interval (hazard ratio, 1.01; 95% CI, 0.94-1.08) was associated with posttransplant survival in either unadjusted or multivariable analyses (both P values >0.6). CONCLUSIONS: Longer duration of brain death was not associated with worse survival following heart transplantation. Donors with prolonged interval of brain death should not necessarily be excluded based on brain death period alone.

Stroke risk following implantation of current generation centrifugal flow left ventricular assist devices.

BACKGROUND AND AIM: Stroke remains a significant complication of left ventricular assist device (LVAD) therapy. We performed a single-center retrospective study evaluating patients undergoing first-time HeartWare HVAD (Medtronic Inc) or HeartMate 3 (Abbott Inc) implantation from September 2009-February 2018. METHODS: Exclusion criteria were age <18 and preoperative ECMO. The primary endpoint was stroke-free survival. Stroke was defined as new neurological deficits persisting >24 hours with corresponding radiographic evidence. Risk factors evaluated included demographics, medical comorbidities, heart failure etiology, LVAD indication, INTERMACS profile, and device type. Univariate predictors (P < .15) and variables clinically suspected to raise stroke risk were entered in a multivariate hazard regression model, specified using backward selection of covariates and accounting for competing risks of transplant/LVAD exchange. RESULTS: A total of 163 HVAD and 84 HM3 patients were analyzed. Median follow up (until death, censoring for transplant/LVAD removal, or end of follow up) was 1.2 years in HVAD patients and 1.4 years in HM3 patients. Stroke occurred in 24 HVAD patients (15 ischemic, 9 hemorrhagic) and 6 HM3 patients (4 ischemic, 2 hemorrhagic). One-year stroke-free survival was 76.8% for HVAD and 84.3% for HM3. Thirty-day mortality following stroke was 41.7% for HVAD and 66.7% for HM3; 54.2% of HVAD strokes were disabling compared to 83.3% of HM3 strokes. Age, LVAD indication, and device type were associated (P < .15) with stroke on univariate analysis. On multivariate analysis, the HVAD was associated with significantly higher stroke risk (hazard ratio, 2.57; 95% confidence interval, 1.02-6.44; P = .045). CONCLUSIONS: Different LVAD models appear to be associated with significantly different stroke risks.