Outcomes of heart transplant recipients bridged with percutaneous versus durable left ventricular assist devices.

BACKGROUND: The new United Network for Organ Sharing (UNOS) heart allocation policy prioritizes temporary percutaneous over durable left ventricular assist devices (LVAD) as bridge to transplant. We sought to examine 1-year outcomes of heart transplant recipients bridged with Impella versus durable LVADs. METHODS: All primary adult orthotopic heart transplant recipients registered in UNOS between January 2016 and June 2021 were analyzed. Recipients were identified as being bridged with isolated durable or percutaneous LVAD at the time of transplant. Baseline characteristics were compared and 1-year survival was examined using the Kaplan Meier method and multivariable Cox proportional hazards regression. RESULTS: During our study period, heart transplant recipients bridged with LVADs were divided between 5422(94%) durable and 324(6%) percutaneous options. Impella-bridged recipients were more likely to be status 1A under the old allocation system (98% vs. 70%, p < .01) and status 2 or higher under the new allocation system (99% vs. 24%, p < .01). Impella-bridged recipients were less likely to be obese (27% vs. 42%, p < .01), have ischemic cardiomyopathy (27% vs. 34%, p < .01), and were more likely to be on inotropic agents at the time of transplant (68% vs. 6%, p < .01). One-year post-transplant survival was not significantly different between the two groups on univariable (HR .87, 95% CI .56-1.37) or multivariable analysis (aHR .63, 95% CI .37-1.07). CONCLUSIONS: Following the UNOS allocation policy change, Impella utilization has increased with no significant difference in 1-year survival compared to bridge with durable LVADs. Impella may be a reasonable alternative to durable LVADs in select patients.

Transcatheter Aortic Valve Replacement for Severe Aortic Valve Stenosis: Do Patients Experience Better Quality of Life Regardless of Gradient?

BACKGROUND: Aortic valve replacement improves survival for patients with low-gradient aortic valve stenosis, but there is a paucity of data on postoperative quality of life for this population. METHODS: In a single-center retrospective analysis of 304 patients with severe aortic valve stenosis who underwent transcatheter aortic valve replacement, patients were divided into 4 groups based on mean pressure gradient, left ventricular ejection fraction, and stroke volume index. Using the Kansas City Cardiomyopathy Questionnaire-12, quality of life was assessed immediately before and 1 month after transcatheter aortic valve replacement. RESULTS: Most patients in the low-flow, low-gradient group were men; this group had higher relative rates of cardiovascular disease and type 2 diabetes than the paradoxical low-flow, low-gradient group; the normal-flow, low-gradient group; and the high-gradient group. All-cause mortality did not differ significantly among the groups at 1 month after surgery, and all groups experienced a significant improvement in quality-of-life scores after surgery. The mean improvement was 27 points in the low-flow, low-gradient group, 25 points in the paradoxical low-flow, low-gradient group, 30 points in the normal-flow, low-gradient group, and 30 points in the high-gradient group (all P < .001). CONCLUSION: Quality of life improves significantly across all subgroups of aortic valve stenosis after trans-catheter aortic valve replacement, regardless of flow characteristics or aortic valve gradients.

Single versus double Perclose techniques for vascular closure during transfemoral transcatheter aortic valve replacement.

INTRODUCTION: The preferred approach for transcatheter aortic valve replacement (TAVR) is transfemoral. There has been widespread adoption of the Perclose ProglideTM device for vascular closure. Typically, two devices are deployed before upsizing the access sheath in the "preclose technique." Prior investigations have compared the use of a single device versus double device technique, but none have shown significant clinical benefit to either approach. METHODS: Five hundred and six patients underwent transfemoral TAVR (TF-TAVR) with single or double Perclose devices for vascular closure from July 2015 to February 2020. A retrospective review was conducted, and propensity-matched analyses were used to account for differences in baseline characteristics. RESULTS: In the matched analysis, there were 251 patients in the single Perclose group and 238 in the double. There was a statistically significant improvement in overall procedural success using the single closure device (94.6% vs. 88.5%, p = 0.009) This was defined as intraprocedural hemostatic control, lack of contrast extravasation, arterial dissection, occlusion, or stenosis >50% in the final crossover angiogram, as well as unimpaired limb perfusion without claudication throughout the index hospitalization. There was also a significant improvement in arterial dissection rates (0.6% vs. 4.6%, p = 0.004), stenosis >50% (1.3% vs. 4.4%, p = 0.028), and Valve Academic Research Consortium major vascular complications (1.8% vs. 4.9%, p = 0.038). CONCLUSION: A single Perclose device is a safe means of vascular closure during TF-TAVR and may have important clinical benefits compared to the commonly used two-device technique.

Nontechnical skills training in cardiothoracic surgery: A pilot study.

OBJECTIVE: The importance of nontechnical skills in surgery is widely recognized. We demonstrate the feasibility of administering and assessing the results of a formal Non-Technical Skills in Surgery (NOTSS) curriculum to cardiothoracic surgery residents. METHODS: Eight cardiothoracic surgery residents participated in the NOTSS curriculum. They were assessed on their cognitive (situation awareness, decision-making) and social (communication and teamwork, leadership) skills based on simulated vignettes. The residents underwent pretraining NOTSS assessments followed by self-administered confidence ratings regarding the 4 skills. Subsequently, a formal NOTSS lecture was delivered and additional readings from the NOTSS textbook was assigned. A month later, the residents returned for post-training NOTSS assessments and self-administered confidence ratings. Changes across days (or within-day before vs after curriculum) were assessed using Wilcoxon signed rank test. RESULTS: There was a significant improvement in the overall NOTSS assessment score (P = .01) as well as in the individual categories (situation awareness, P = .02; decision-making, P = .02; communication and teamwork, P = .01; leadership, P = .02). There was also an increase in resident self-perception of improvement on the post-training day (P = .01). CONCLUSIONS: We have developed a simulation-based NOTSS curriculum in cardiothoracic surgery that can be formally integrated into the current residency education. This pilot study indicates the feasibility of reproducible assessments by course educators and self-assessments by participating residents in nontechnical skills competencies.

Validity of echocardiography for detection of left ventricular thrombus with surgical validation in patients awaiting durable left ventricular assist device.

OBJECTIVE: Unrecognized left ventricular thrombi (LVT) can have devastating clinical implications and precludes patients with end-stage heart failure from undergoing left ventricular assist device (LVAD) implantation without cardiopulmonary bypass assistance. We assessed the reliability of an echocardiogram to diagnose LVT in patients with end-stage heart disease who underwent LVAD implantation. METHODS: A single-center retrospective study evaluated 232 consecutive adult patients requiring implantation of durable LVADs between 2005 and 2019. The validity of preoperative transthoracic echocardiogram (TTE) and intraoperative transesophageal echocardiogram (TEE) for diagnosing LVT was compared to direct inspection at the time of LVAD implantation. RESULTS: There were 232 patients that underwent LVAD implantation, with 226 patients (97%) receiving a preoperative TTE. Of those 226 patients, 32 patients (14%) received ultrasound enhancing agents (UEA). Intraoperative TEE images were available in 195 patients (84%). The sensitivity of TTE without UEA was 22% and specificity was 90% for detecting LVT, compared to 50% and 86%, respectively, for TTE with UEA. For intraoperative TEE, the sensitivity and specificity were 46% and 96%, respectively. The false omission rate ranged from 4% to 8% for all modalities of echocardiography. CONCLUSION: Among patients undergoing LVAD implantation, preoperative TTE and intraoperative TEE had poor sensitivity for LVT detection. Up to 8% of echocardiograms were incorrectly concluded to be negative for LVT on surgical validation. The low sensitivity and positive predictive value for diagnosing LVT suggest that echocardiography has limited reliability in this cohort of patients who are at high risk of LVT formation and its subsequent complications.

Minimally Invasive Repair of Ascending Aortic Pseudoaneurysms: An Alternative to Open Surgical Repair in High-Risk Patients.

Development of a pseudoaneurysm of the ascending aorta is an uncommon complication of aortic surgery. Several nonsurgical techniques are available for treatment of ascending aortic pseudoaneurysms (AAPs). This report outlines a single-center retrospective experience with 14 nonsurgical procedures for treatment of AAPs in 10 patients. Modified stent grafts, septal defect occlusion devices, coil embolics, and liquid embolics were deployed by transthoracic and endovascular approaches. Complete stasis of the AAP was achieved in 7 of 10 patients (70%). Mean postprocedural recoveries occurred within 3.5 days. Nonsurgical techniques for repair of AAPs offer a comparatively safe and effective alternative to open surgical repair.

Discovery of non-HLA antibodies associated with cardiac allograft rejection and development and validation of a non-HLA antigen multiplex panel: From bench to bedside.

We analyzed humoral immune responses to nonhuman leukocyte antigen (HLA) after cardiac transplantation to identify antibodies associated with allograft rejection. Protein microarray identified 366 non-HLA antibodies (>1.5 fold, P < .5) from a discovery cohort of HLA antibody-negative, endothelial cell crossmatch-positive sera obtained from 12 cardiac allograft recipients at the time of biopsy-proven rejection. From these, 19 plasma membrane proteins and 10 autoantigens identified from gene ontology analysis were combined with 48 proteins identified through literature search to generate a multiplex bead array. Longitudinal sera from a multicenter cohort of adult cardiac allograft recipients (samples: n = 477 no rejection; n = 69 rejection) identified 18 non-HLA antibodies associated with rejection (P < .1) including 4 newly identified non-HLA antigenic targets (DEXI, EMCN, LPHN1, and SSB). CART analysis showed 5/18 non-HLA antibodies distinguished rejection vs nonrejection. Antibodies to 4/18 non-HLA antigens synergize with HLA donor-specific antibodies and significantly increase the odds of rejection (P < .1). The non-HLA panel was validated using an independent adult cardiac transplant cohort (n = 21 no rejection; n = 42 rejection, >1R) with an area under the curve of 0.87 (P < .05) with 92.86% sensitivity and 66.67% specificity. We conclude that multiplex bead array assessment of non-HLA antibodies identifies cardiac transplant recipients at risk of rejection.

Height mismatch: An overlooked component of adult heart transplant outcomes.

Heart transplantation guidelines recommend against matching donors with significant weight but not height discrepancies. This study analyzed the impact of donor-recipient height mismatch on mortality among heart transplant recipients. We retrospectively analyzed all adult patients in the United Network for Organ Sharing (UNOS) registry undergoing heart transplantation from 1990 to September 2016. Moderate and severe height mismatch were classified as >10% and >15% difference in donor height from recipient height, respectively. The primary outcome was 1-year mortality. Adjusted Cox hazards regression was performed, and Kaplan-Meier estimates illustrated 10-year survival. Of 44 877 transplants, 4822 (10.7%) were moderately height mismatched. Height-mismatched recipients were more frequently female (41.6% vs 21.8%, P < .001), sex mismatched (53.8% vs 24.9%, P < .001), and weight mismatched (4.9% vs 1.9%, P < .001). After adjustment, recipients of moderately (HR = 1.15 [1.02-1.30]) and severely (HR = 1.38 [1.10-1.74]) taller donor hearts were at increased risk of mortality at 1 year relative to height-matched recipients. Furthermore, of 1042 (21.6%) severe mismatches, recipients with taller (HR = 1.39 [1.11-1.74]) but not shorter (HR = 0.79 [0.44-1.43]) donors faced increased 10-year mortality. The effect was pronounced among re-transplant candidates (HR = 1.96 [1.07-3.59]). In conclusion, matching with moderately or severely taller donors is an independent predictor of mortality among primary and re-transplant candidates.

Temporal expression of cytokines and B-cell phenotypes during mechanical circulatory support.

BACKGROUND: Allosensitization during mechanical circulatory support (MCS) is a well-described phenomenon, although its mechanism remains unknown. Although immune-mediated interactions from devices or blood transfusions have been proposed, the role of inflammation in this development is less clear. This study was undertaken to further investigate the temporal association of cytokines and B-cell phenotypes in the MCS population. METHODS: Adult patients who received the Heartmate II (Thoratec, Pleasanton, Calif) at our center between September 2012 and March 2015 were prospectively followed after device implantation. Blood draws for anti-human leukocyte antigen (HLA) antibody, cytokine expression, and B-cell immunophenotyping were performed before implantation and for 3 weeks postoperatively. Time courses for cytokines and B-cell subsets were expressed using visual representations of median levels as heat maps, and mixed modeling analysis was used to model changes with time and patient factors. RESULTS: Twenty patients who received the Heartmate II (Thoratec) were analyzed during the study period. Four patients showed measureable levels of anti-HLA antibody during the follow-up period, although 3 of these had evidence of antibodies preoperatively. Analysis of cytokine trends revealed early (interleukin [IL]-6, IL-8, and IL-10) and late peaking (IL-3, IL-4, fibroblast growth factor 2, and CD40L) patterns. Upregulation of switched memory, transitional, and plasma blast B cells occurred over time. Right ventricular assist device use and low Interagency Registry for Mechanically Assisted Circulatory Support score were associated with decreased mature naive and increased antibody-secreting cells. CONCLUSIONS: MCS device implantation was associated with increased inflammatory cytokines and maturation of B-cell phenotypes. No patients developed de novo HLA antibodies, whereas several showed increases in anti-HLA antibody levels detected before implantation. This suggests that inflammation and maturation of existing sensitized B cells might play an important role in the pathogenesis of allosensitization in MCS.

Understanding lung transplant listing practices: Survival in lung transplant candidates who improve clinically to delisting.

BACKGROUND: Occasionally, lung transplant candidates improve to the point where they are removed from the transplant list. We sought to determine the characteristics and outcomes of lung transplant candidates who improved to delisting both before and after implementation of the lung allocation score. METHODS: Using the United Network for Organ Sharing database, we reviewed all adult patients listed for lung transplant between 1987 and 2012. The last permanent status change was classified into transplanted, improved to delisting (improved), or deteriorated to delisting (deteriorated). Survival time was calculated using the linked date of death from the Social Security Administration. Survival analysis was performed via the Kaplan-Meier method, and adjusted multivariable logistic regressions identified characteristics predicting improvement to delisting. RESULTS: Of 13,688 candidates, 12,188 (89.0%) were transplanted, 454 (3.3%) improved, and 1,046 (7.6%) deteriorated. The 5-year mortality was greater in improved (hazard ratio = 1.21 [1.07-1.38], P = .002) and deteriorated (hazard ratio = 3.36 [3.11-3.64], P < .001) candidates relative to those transplanted; however, 1-year survival was greater in improved versus transplanted candidates (75.9% vs 67.2%, log rank P < .001). Older, female patients listed for primary pulmonary hypertension and retransplantation were more likely to improve to delisting. The proportion of improved patients varied by hospital quartile volume (P < .001) and the United Network for Organ Sharing geographic region (P < .001). The number of patients improving to delisting decreased after implementation of the lung allocation score. CONCLUSION: Lung transplant candidates improving to delisting faced less short-term but greater long-term mortality relative to transplanted candidates. Given that the improved population decreased dramatically after implementation of the lung allocation score, redefining patient listing criteria appears to have improved patient appropriateness for transplant.

Use of a Covered CP Stent to Exclude an Aortic-Brachiocephalic Conduit Pseudoaneurysm.

A 63-year-old woman was incidentally found to have a thoracic aortic aneurysm. We performed hybrid repair involving aortic arch debranching and endovascular stent-graft placement. Four months later, an asymptomatic pseudoaneurysm had formed at the aortic conduit-brachiocephalic artery anastomosis. To exclude the pseudoaneurysm, we deployed a Covered CP Stent across the anastomosis through a surgically created right axillary artery conduit. We discuss the patient's case and our choice of treatment.

Pretransplant malignancy among lung transplant recipients in the modern era.

BACKGROUND: Malignancy is a relative contraindication in transplant candidates, given the increased neoplastic risk accompanying posttransplant immunosuppression. However, the number of patients receiving a lung transplant despite pretransplant malignancy is rising, and their outcomes remain unclear. Our purpose was to examine the outcomes of lung transplant recipients with pretransplant malignancy in the modern era. METHODS: We evaluated the United Network for Organ Sharing registry for adult lung transplants that were completed between June 2005 and September 2016. Transplant recipients were stratified by pretransplant malignancy, with subgroup analysis by sex and active malignancy. The primary outcome was 5-year survival and the secondary outcome was cause of death. Kaplan-Meier estimates illustrated 5-year survival and multivariable Cox proportional hazards regressions controlled for demographics and comorbidities. RESULTS: Of 18,032 transplant patients, 1,321 transplant recipients (7.3%) possessed a pretransplant malignancy. Patients with pretransplant malignancy faced significantly greater mortality within 5 years (36.0% vs 32.8%, P = .017), an effect greatest in men with pretransplant malignancy (39.2% vs 33.7%, P = .002). Patients with pretransplant malignancy also faced greater risk of death from posttransplant malignancy (15.6% vs 9.4%, P < .001), particularly for those with active malignancy at transplant (34.8% vs 9.8%, P < .001). Pretransplant malignancy remained a significant predictor of 5-year mortality in adjusted Cox regressions (hazard ratio: 1.16 [1.05-1.27], P = .003). CONCLUSION: Patients with pretransplant malignancy, and particularly men with pretransplant malignancy and those with active malignancy at transplant, are at an increased risk of 5-year mortality and posttransplant death from malignancy. Balancing individual risk of posttransplant malignancy with immunosuppressive care is necessary to optimize outcomes for pretransplant malignancy patients.

Association of pro-inflammatory cytokines and monocyte subtypes in older and younger patients on clinical outcomes after mechanical circulatory support device implantation.

Noninvasive immunologic analysis of peripheral blood holds promise for explaining the mechanism of development of adverse clinical outcomes, and may also become a method for patient risk stratification before or after mechanical circulatory support device (MCSD) implantation. Dysregulation of the innate immune system is associated with increased patient age but has yet to be evaluated in the older patient with advanced heart failure undergoing MCSD surgery. Patients pre- and post-MCSD implantation had peripheral blood mononuclear cells (PBMC) and serum isolated. Multiparameter flow cytometry was used to analyze markers of innate cell function, including monocyte subtypes. Multiplex cytokine analysis was performed. MELD-XI and SOFA scores were utilized as surrogate markers of outcomes. Increased levels of pro-inflammatory cytokines including IL-15, TNF-α, and IL-10 were associated with increased MELD-XI and SOFA scores. IL-8, TNF- α, and IL-10 were associated with risk of death after MCSD implantation, even with correction for patient age. Increased frequency of 'classical' monocytes (CD14 + CD16-) were associated with increased MELD-XI and SOFA scores. This suggests that inflammation and innate immune system activation contribute to progression to multiorgan system failure and death after MCSD surgery. Development of noninvasive monitoring of peripheral blood holds promise for biomarker development for candidate selection and patient risk stratification.

Understanding the Correlation Between DSA, Complement Activation, and Antibody-Mediated Rejection in Heart Transplant Recipients.

BACKGROUND: Donor-specific HLA antibodies (DSA) are associated with increased rates of rejection and of graft failure in cardiac transplantation. The goal of this study was to determine the association of preformed and posttransplant development of newly detected DSA (ndDSA) with antibody-mediated rejection (AMR) and characterize the clinical relevance of complement-activating DSA in heart allograft recipients. METHODS: The study included 128 adult and 48 pediatric heart transplant patients transplanted between 2010 and 2013. Routine posttransplant HLA antibody testing was performed by IgG single-antigen bead test. The C3d single-antigen bead assay was used to identify complement-activating antibodies. Rejection was diagnosed using International Society for Heart and Lung Transplantation criteria. RESULTS: In this study, 22 patients were transplanted with preexisting DSA, and 43 patients developed ndDSA posttransplant. Pretransplant (P < 0.05) and posttransplant (P < 0.001) ndDSA were associated with higher incidence of AMR. Patients with C3d + DSA had significantly higher incidence of AMR compared with patients with no DSA (P < 0.001) or patients with C3d-DSA (P = 0.02). Nine (36%) of 25 patients with AMR developed transplant coronary artery disease compared with 17 (15.9%) of 107 patients without AMR (P < 0.05). Among the 47 patients who received ventricular assistant device (VAD), 7 of 9 VAD+ patients with preformed DSA experienced AMR compared with 7 of 38 VAD+ patients without preformed DSA, indicating presensitization to donor HLA significantly increased the risk of AMR (P < 0.01). CONCLUSIONS: Preformed and posttransplant ndDSA were associated with AMR. C3d + DSA correlates with complement deposition on the graft and higher risk of AMR which may permit the application of personalized immunotherapy targeting the complement pathway.

Distal Left Main Coronary Artery Aneurysm Resection during 5-Vessel Coronary Artery Bypass Grafting.

Coronary artery aneurysms are abnormal dilations of arterial segments, in some cases associated with underlying atherosclerosis. Although affected patients can be asymptomatic, some are at risk of plaque rupture, dissection, and other complications. Investigations into the optimal management of these vascular malformations are ongoing, because no consensus exists regarding when and how best to intervene. We present the case of a 58-year-old man whose large left main coronary artery aneurysm we ligated and removed during 5-vessel coronary artery bypass grafting. This distal aneurysm was at the trifurcation level of the patient's left anterior descending and left circumflex coronary arteries. In addition, we discuss considerations about left main coronary artery aneurysms and their treatment.

Clinical phenomapping and outcomes after heart transplantation.

BACKGROUND: Survival after heart transplantation (HTx) is limited by complications related to alloreactivity, immune suppression, and adverse effects of pharmacologic therapies. We hypothesize that time-dependent phenomapping of clinical and molecular data sets is a valuable approach to clinical assessments and guiding medical management to improve outcomes. METHODS: We analyzed clinical, therapeutic, biomarker, and outcome data from 94 adult HTx patients and 1,557 clinical encounters performed between January 2010 and April 2013. Multivariate analyses were used to evaluate the association between immunosuppression therapy, biomarkers, and the combined clinical end point of death, allograft loss, retransplantation, and rejection. Data were analyzed by K-means clustering (K = 2) to identify patterns of similar combined immunosuppression management, and percentile slopes were computed to examine the changes in dosages over time. Findings were correlated with clinical parameters, human leucocyte antigen antibody titers, and peripheral blood mononuclear cell gene expression of the AlloMap (CareDx, Inc., Brisbane, CA) test genes. An intragraft, heart tissue gene coexpression network analysis was performed. RESULTS: Unsupervised cluster analysis of immunosuppressive therapies identified 2 groups, 1 characterized by a steeper immunosuppression minimization, associated with a higher likelihood for the combined end point, and the other by a less pronounced change. A time-dependent phenomap suggested that patients in the group with higher event rates had increased human leukocyte antigen class I and II antibody titers, higher expression of the FLT3 AlloMap gene, and lower expression of the MARCH8 and WDR40A AlloMap genes. Intramyocardial biomarker-related coexpression network analysis of the FLT3 gene showed an immune system-related network underlying this biomarker. CONCLUSIONS: Time-dependent precision phenotyping is a mechanistically insightful, data-driven approach to characterize patterns of clinical care and identify ways to improve clinical management and outcomes.