Late Follow-up for a Randomized Trial of Surgical Treatment of Tricuspid Valve Regurgitation in Patients Undergoing Left Ventricular Assist Device Implantation.

OBJECTIVES: We previously reported that concurrent tricuspid valve surgery (TVS) was not associated with a lower incidence of early RHF among patients undergoing durable LVAD implantation. This is a follow-up analysis to further define the clinical impact of concurrent TVS within 12-months of follow-up. METHODS: Patients with moderate or severe TR on pre-operative echocardiography (n=71) were randomized to either LVAD implantation alone (No TVS, n=34) or with concurrent TVS (TVS, n=37). Randomization was stratified by pre-operative right ventricular dysfunction. Patients were followed for at least 12-months after surgery. The incidence of RHF was determined using INTERMACS criteria by an adjudication committee. Functional studies and repeat echocardiography were performed at 12-months. RESULTS: Demographics were similar between the two arms. At 12-months, the rate of moderate or severe RHF was 50.0% (No TVS) versus 51.4% (TVS). No patients developed RHF between 6- and 12-months following the procedure. Death from RHF was 5.4% (TVS) versus 8.8% (No TVS). At 12-months, there was no significant difference in TR severity between the two arms due to improvement in TR severity in the No TVS arm. On cardiopulmonary exercise testing at 12+ months, there was no significant difference in peak oxygen consumption. CONCLUSIONS: In patients with significant pre-implant TR, the severity of TR improved over time in the LVAD implantation alone arm. By 12-months, there is no significant difference in TR severity between the two arms. This may account for the lack of difference in late clinical or functional parameters.

Evaluating threshold for donor fraction cell-free DNA using clinically available assay for rejection in pediatric and adult heart transplantation.

BACKGROUND: The aims of the study were to assess the performance of a clinically available cell-free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection. METHODS: Observational, non-interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy-associated plasma samples were used for cfDNA measurements. Pre-determined cut points were tested for analytic performance. RESULTS: A total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df-cfDNA values between rejection [0.21% (IQR 0.12-0.69)] and healthy samples [0.05% (IQR 0.01-0.14), p < .0001]. The pediatric rejection group had a median df-cfDNA value of 0.93% (IQR 0.28-2.84) compared to 0.09% (IQR 0.04-0.23) for healthy samples, p = .005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection. CONCLUSION: The study suggests that pediatric patients with rejection show higher levels of circulating df-cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance.

Long-term predictors of morbidity and mortality in patients following LVAD replacement.

BACKGROUND: As heart transplant guidelines evolve, the clinical indication for 73% of durable left ventricular assist device (LVAD) implants is now destination therapy. Although completely magnetically levitated LVAD devices have demonstrated improved durability relative to previous models, LVAD replacement procedures are still required for a variety of indications. Thus, the population of patients with a replaced LVAD is growing. There is a paucity of data regarding the outcomes and risk factors for those patients receiving first-time LVAD replacements. METHODS: The study cohort consisted of all consecutive patients between 2006 and 2020 that received a first-time LVAD replacement at a single institution. Preoperative clinical and laboratory variables were collected retrospectively. The primary endpoint was death or need for an additional LVAD replacement. Data were subjected to Kaplan-Meier, univariate, and multivariate Cox hazard ratio analyses. RESULTS: In total, 152 patients were included in the study, of which 101 experienced the primary endpoint. On multivariate analysis, patients receiving HeartMate 3 (HM3) LVADs as the replacement device showed superior outcomes (HR 0.15, 95% CI 0.065-0.35, p < 0.0001). Independent risk factors for death or need for additional replacement included preoperative extracorporeal membrane oxygenation (ECMO) (HR 4.44, 95% CI 1.87-14.45, and p = 0.00042), increased number of sternotomies (HR 5.20, 95% CI 1.87-14.45, and p = 0.0016), and preoperative mechanical ventilation (HR 1.98, 95% CI 1.01-3.86, and p = 0.045). CONCLUSIONS: Replacement with HM3 showed superior outcomes compared to all other pump types when controlling for both initial pump type and other independent predictors of death or LVAD replacement. Preoperative ECMO, mechanical ventilation, and multiple sternotomies also increased the odds for death or the need for subsequent replacement.

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.

Ex Vivo Gene Delivery to Porcine Cardiac Allografts Using a Myocardial-Enhanced Adeno-Associated Viral Vector.

Transplantation, the gold standard intervention for organ failure, is a clinical field that is ripe for applications of gene therapy. One of the major challenges in applying gene therapy to this field is the need for a method that achieves consistent and robust gene delivery to allografts. Normothermic ex vivo perfusion is a growing organ preservation method and a device for cardiac preservation was recently approved by the Food and Drug Administration (FDA) (Organ Care System, OCS™; TransMedics, Inc., Andover, MA); this device maintains donor hearts in a near physiologic state while they are transported from the donor to the recipient. This study describes the administration of recombinant adeno-associated viral vectors (rAAVs) during ex vivo normothermic perfusion for the delivery of transgenes to porcine cardiac allografts. We utilized a myocardial-enhanced AAV3b variant, SASTG, assessing its transduction efficiency in the OCS perfusate relative to other AAV serotypes. We describe the use of normothermic ex vivo perfusion to deliver SASTG carrying the Firefly Luciferase transgene to porcine donor hearts in four heterotopic transplant procedures. Durable and dose-dependent transgene expression was achieved in the allografts in 30 days, with no evidence of off-target transgene expression. This study demonstrates the feasibility and efficiency of delivering genes to a large animal allograft utilizing AAV vectors during ex vivo perfusion. These findings support the idea of gene therapy interventions to enhance transplantation outcomes.

Selective Sinus Replacement for Aortic Root Aneurysm: Durable Approach in Selected Patients.

BACKGROUND: Selective sinus replacement (SSR) allows a tailored repair approach in patients with sinus of Valsalva or asymmetric aortic root aneurysm. SSR avoids the need for coronary reimplantation for nondiseased sinuses and shortens operative time, although potential for late growth of retained sinuses exists. This study describes selection of patients and assesses operative outcomes and late root dimensions after SSR. METHODS: From 2006 to 2020, 60 patients underwent SSR at a single referral institution. Mixed effect models were used to assess trajectory of postoperative growth of remaining sinuses, adjusting for age of the patient, valve morphology, and baseline root diameter. RESULTS: Median age of the patients was 57 (interquartile range [IQR], 48-65) years. Twenty-four (40%) had a bicuspid aortic valve. Most patients (n = 55 [92%]) underwent single sinus replacement (n = 46 noncoronary, n = 9 right), whereas 5 (8%) underwent repair of both the right and noncoronary sinuses. Concomitant aortic valve replacement was performed in 15 patients (25%); aortic valve repair with internal ring annuloplasty or cusp plication was performed in 37 (62%). There was no operative death, stroke, renal failure, or respiratory failure. Median preoperative root diameter was 53 mm (IQR, 51-56 mm) vs 42 mm (IQR, 39-45 mm) at median imaging follow-up of 34 (IQR, 13-49) months. Rate of midterm root growth was 0.2 mm/y, and there were no late root reinterventions. CONCLUSIONS: For patients with sinus of Valsalva or asymmetric root aneurysm, SSR is associated with excellent operative outcomes, and midterm follow-up suggests that the technique is durable. Longer term follow-up is needed to confirm continued stability of the aortic root.

Validation of donor fraction cell-free DNA with biopsy-proven cardiac allograft rejection in children and adults.

OBJECTIVES: Donor-specific cell-free DNA shows promise as a noninvasive marker for allograft rejection, but as yet has not been validated in both adult and pediatric recipients. The study objective was to validate donor fraction cell-free DNA as a noninvasive test to assess for risk of acute cellular rejection and antibody-mediated rejection after heart transplantation in pediatric and adult recipients. METHODS: Pediatric and adult heart transplant recipients were enrolled from 7 participating sites and followed for 12 months or more with plasma samples collected immediately before all endomyocardial biopsies. Donor fraction cell-free DNA was extracted, and quantitative genotyping was performed. Blinded donor fraction cell-free DNA and clinical data were analyzed and compared with a previously determined threshold of 0.14%. Sensitivity, specificity, negative predictive value, positive predictive value, and receiver operating characteristic curves were calculated. RESULTS: A total of 987 samples from 144 subjects were collected. After applying predefined clinical and technical exclusions, 745 samples from 130 subjects produced 54 rejection samples associated with the composite outcome of acute cellular rejection grade 2R or greater and pathologic antibody-mediated rejection 2 or greater and 323 healthy samples. For all participants, donor fraction cell-free DNA at a threshold of 0.14% had a sensitivity of 67%, a specificity of 79%, a positive predictive value of 34%, and a negative predictive value of 94% with an area under the curve of 0.78 for detecting rejection. When analyzed independently, these results held true for both pediatric and adult cohorts at the same threshold of 0.14% (negative predictive value 92% and 95%, respectively). CONCLUSIONS: Donor fraction cell-free DNA at a threshold of 0.14% can be used to assess for risk of rejection after heart transplantation in both pediatric and adult patients with excellent negative predictive value.

Cardiovascular mechanism of donor brain death and heart recipient survival.

BACKGROUND: Heart donation after donor brain death from cardiac arrest despite successful resuscitation may be associated with worse recipient outcomes due to potential graft ischemia or underlying rhythmic/structural defects. However, selected grafts from such donors often have normal cardiac function and anatomy. We investigated whether a cardiovascular mechanism of donor brain death (CV-DBD) was associated with worse recipient outcomes. METHODS: We queried the United Network for Organ Sharing (UNOS) database for first-time, single-organ, adult (age 18+) heart transplant recipients and their associated donors between January 2005 and March 2021. Recipients were stratified by donor status (CV-DBD vs. non-CV-DBD). We performed multivariable Cox proportional hazards modeling to ascertain whether receiving a CV-DBD graft was independently associated with mortality. RESULTS: Of 35,833 included recipients, 2,702 (7.5%) received CV-DBD grafts. The associated donors were significantly more likely to be female, older, and have a history of diabetes, hypertension, and substance use (all p < .001). On unadjusted Kaplan-Meier analysis, CV-DBD recipients had a significantly reduced median survival than non-CV-DBD recipients (12.0 vs. 13.1 years, log-rank p = .04). However, after adjusting for donor/recipient age, recipient comorbidities, annualized center volume, and transplantation era, CV-DBD organ status was not associated with recipient mortality (hazard ratio: 1.05, 95% confidence interval: 0.96-1.13, p = .28). CONCLUSION: In this analysis of over 35,000 heart transplants, CV-DBD status was not associated with adjusted recipient survival. Donor brain death due to cardiac arrest should not be an absolute contraindication to heart donation, although graft function should be carefully assessed before transplantation.

Relationship between donor fraction cell-free DNA and clinical rejection in heart transplantation.

BACKGROUND: Clinical rejection (CR) defined as decision to treat clinically suspected rejection with change in immunotherapy based on clinical presentation with or without diagnostic biopsy findings is an important part of care in heart transplantation. We sought to assess the utility of donor fraction cell-free DNA (DF cfDNA) in CR and the utility of serial DF cfDNA in CR patients in predicting outcomes of clinical interest. METHODS: Patients with heart transplantation were enrolled in two sequential, multi-center, prospective observational studies. Blood samples were collected for surveillance or clinical events. Clinicians were blinded to the results of DF cfDNA. RESULTS: A total of 835 samples from 269 subjects (57% pediatric) were included for this analysis, including 28 samples associated with CR were analyzed. Median DF cfDNA was 0.43 (IQR 0.15, 1.36)% for CR and 0.10 (IQR 0.07, 0.16)% for healthy controls (p < .0001). At cutoff value of 0.13%, the area under curve (AUC) was 0.82, sensitivity of 0.86, specificity of 0.67, and negative predictive value of 0.99. There was serial decline in DF cfDNA post-therapy, however, those with cardiovascular events (cardiac arrest, need for mechanical support or death) showed significantly higher levels of DF cfDNA on Day 0 (2.11 vs 0.31%) and Day 14 (0.51 vs 0.22%) compared to those who did not have such an event (p < .0001). CONCLUSION: DF cfDNA has excellent agreement with clinical rejection and, importantly, serial measurement of DF cfDNA predict clinically significant outcomes post treatment for rejection in these patients.

Progression of aortic valve insufficiency during centrifugal versus axial flow left ventricular assist device support.

OBJECTIVES: Long-term left ventricular assist device (LVAD) support can cause accelerated progression of aortic insufficiency (AI). The MOMENTUM trial has led to increased use of the HeartMate 3 (HM3) LVAD, due to greater hemocompatibility. However, the differential effect on the rate of progression of AI during HM3 support versus HeartMate 2 (HM2) has not been extensively studied. This analysis compares the rates of progression to moderate or severe AI (MSAI) comparing a cohort of patients supported with the HM2 versus HM3. METHODS: A retrospective review was performed on all consecutive patients implanted with HM2 or HM3 between May 2005 and June 2020. Follow-up time was limited to the first 6 years after LVAD implantation. Demographics and 4005 echocardiograms were assessed for 536 HM2 and 300 HM3 patients. The primary end point was progression to MSAI. Univariable and multivariable Cox proportional hazard regression and landmark analyses were performed. RESULTS: Progression to MSAI was greater in the HM2 (17%) versus HM3 (9.9%) cohort. On the univariable analysis, the hazard ratio for HM3 was 0.581 (95% confidence interval 0.370-0.909, P = 0.02) whereas on multivariable analysis hazard ratio was 0.624 (95% confidence interval 0.386-1.008, P = 0.0537). Preoperative AI, female sex and body surface area <2 were significantly associated with progression to MSAI. Landmark analysis suggests that LVAD type has the most significant effect on progression to MSAI between 1 and 2 years post-implantation. CONCLUSIONS: Current practice strategies achieved low rates of progression to MSAI. Preoperative AI, female sex and body surface area <2 were the most important predictors of progression to MSAI. Pump type appears to be of secondary importance.

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.

Incidence and Diagnostic Challenges of Bowel Ischemia after Continuous-flow Left Ventricular Assist Device Therapy.

Long-term continuous-flow left ventricular assist device (CFLVAD) therapy is limited by complications. Compared with stroke and renal dysfunction, post-CFLVAD bowel ischemia is poorly characterized. Adult patients who underwent first-time durable CFLVAD implantation at our institution between 2008 and 2018 were identified and screened for bowel ischemia using Current Procedural Terminology codes for abdominal surgical exploration and International Classification of Disease codes for intestinal vascular insufficiency. Patients who developed biopsy-proven bowel ischemia (cases) were matched to controls (1:1, nearest neighbor, caliper = 0.29) based on preoperative characteristics. Incidences of postoperative right heart failure and renal replacement therapy were compared using McNemar's test. One year survival was estimated using the Kaplan-Meier method. Overall, 711 patients underwent CFLVAD implantation. Nineteen (2.7%) developed bowel ischemia (cases) median 17 days postimplantation (IQR 8-71). The majority of cases were male (78.9%), Black (63.2%), received HeartMate II (57.9%), treated as destination therapy (78.9%), and had a history of hypertension (89.5%), chronic kidney disease (84.2%), hyperlipidemia (84.2%), smoking (78.9%), and atrial fibrillation (57.9%). Post-LVAD, case patients were more likely to develop moderate-severe right heart failure (89.5% vs. 68.4%, p = 0.005), require renal replacement therapy (21.1% vs. 0%, p < 0.001), and less likely to survive to discharge (52.6% vs. 89.5%, p = 0.02) compared with controls. Case subjects demonstrated worse 1 year survival. While less common than stroke and renal dysfunction, post-CFLVAD bowel ischemia is associated with high 1 year mortality. Multi-institutional registries should consider reporting abdominal complications such as bowel ischemia as an adverse event to further investigate these trends and identify predictors of this complication to reduce patient mortality.

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.

Does deeper hypothermia reduce the risk of acute kidney injury after circulatory arrest for aortic arch surgery?

OBJECTIVES: The impact of hypothermic circulatory arrest (HCA) temperature on postoperative acute kidney injury (AKI) has not been evaluated. This study examined the association between circulatory arrest temperatures and AKI in patients undergoing proximal aortic surgery with HCA. METHODS: A total of 759 consecutive patients who underwent proximal aortic surgery (ascending ± valve ± root) including arch replacement requiring HCA between July 2005 and December 2016 were identified from a prospectively maintained institutional aortic surgery database. The primary outcome was AKI as defined by Risk, Injury, Failure, Loss, End Stage Renal Disease (ESRD) criteria. The association between minimum nasopharyngeal (NP) and bladder temperatures during HCA and postoperative AKI was assessed, adjusting for patient-level factors using multivariable logistic regression. RESULTS: A total of 85% (n = 645) of patients underwent deep hypothermia (14.1-20.0°C), 11% (n = 83) low-moderate hypothermia (20.1-24.0°C) and 4% (n = 31) high-moderate hypothermia (24.1-28.0°C) as classified by NP temperature. When analysed by bladder temperature, 59% (n = 447) underwent deep hypothermia, 22% (n = 170) low-moderate, 16% (n = 118) high-moderate and 3% mild (n = 24) (28.1-34.0°C) hypothermia. The median systemic circulatory arrest time was 17 min. The incidence of AKI did not differ between hypothermia groups, whether analysed using minimum NP or bladder temperature. In the multivariable analysis, the association between degree of hypothermia and AKI remained non-significant whether analysed as a categorical variable (hypothermia group) or as a continuous variable (minimum NP or bladder temperature) (all P > 0.05). CONCLUSIONS: In patients undergoing proximal aortic surgery including arch replacement requiring HCA, degree of systemic hypothermia was not associated with the risk of AKI. These data suggest that moderate hypothermia does not confer increased risk of AKI for patients requiring circulatory arrest, although additional prospective data are needed.

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.

Activated Coagulation Time and Hepcon Protamine Titration Device to Manage Unfractionated Heparin During Cardiopulmonary Bypass in a Hemophilia A Patient on Emicizumab.

In the perioperative management of patients with hemophilia A, emicizumab prevents the accurate measurement of common clotting assays, including the activated clotting time (ACT), which is essential for high-dose heparin monitoring during cardiopulmonary bypass surgery. The authors describe the successful perioperative management of a hemophilia A patient on maintenance emicizumab who, following a non-ST myocardial infarction, underwent cardiopulmonary bypass grafting surgery with heparin monitoring using both the ACT and heparin levels from the Hepcon protamine titration device. Postoperatively, the patient was transitioned to recombinant factor VIII replacement therapy. In hemophilia A patients on emicizumab who require heparin titration on cardiopulmonary bypass surgery, the ACT, combined with Hepcon heparin levels, may be used to complete the surgery successfully without excessive bleeding or morbidity.

Heart Transplantation Survival Outcomes of HIV Positive and Negative Recipients.

BACKGROUND: In the era of antiretroviral therapy, HIV-positive patients have reduced mortality from HIV infection and increased morbidity from end-stage heart failure. The number of HIV-positive heart transplantation recipients remains scant. Long-term survival has not been rigorously studied. We compared survival outcomes of heart transplantation in HIV-positive recipients with those of HIV-negative recipients. METHODS: Clinical data from all adult heart transplantations were extracted from the United Network for Organ Sharing dataset. The impact of recipient HIV status was analyzed with Cox proportional hazards modeling, 1:3 propensity score matching, and Kaplan-Meier survival analysis. RESULTS: Seventy-five HIV-positive recipients and 29,848 HIV-negative recipients were identified. Race distributions differed between the recipient groups, with black patients comprising a larger proportion of the HIV-positive recipient group (46.7% vs 20.9%, P < .001). The mean year of transplant was significantly later in the HIV-positive recipient group. The rate of acute rejection in the HIV-positive group was higher than in the HIV-negative group (38.7% vs 17.7%, P < .001), as was rate of antirejection treatment administration such as intravenous immunoglobulin or plasmapheresis (26.7% vs 10.4%, P < .001). There was no difference in 30-day, 1-year, and 5-year survival of HIV-positive recipients vs HIV-negative recipients. Recipient HIV infection was not a significant covariate in predicting survival in a Cox proportional hazards model. CONCLUSIONS: Short-term and moderate-term survival after heart transplantation is similar for HIV-positive recipients and HIV-negative recipients, although data are very limited. This finding suggests that HIV-positive recipients should not be excluded from transplant candidacy solely based on HIV serostatus.