Bridging strategies and cardiac replacement outcomes in patients with acute decompensated heart failure-related cardiogenic shock.

AIMS: To describe outcomes associated with bridging strategies in patients with acute decompensated heart failure-related cardiogenic shock (ADHF-CS) bridged to durable left ventricular assist device (LVAD) or heart transplantation (HTx). METHODS AND RESULTS: Durable LVAD or HTx recipients from 2014 to 2019 with pre-operative ADHF-CS were identified in the Society of Thoracic Surgeons Adult Cardiac Surgery Database and stratified by bridging strategy. The primary outcome was operative or 30-day post-operative mortality. Secondary outcomes included post-operative major bleeding. Exploratory comparisons between bridging strategies and outcomes were performed using overlap weighting with and without covariate adjustment. Among 9783 patients with pre-operative CS, 8777 (89.7%) had ADHF-CS. Medical therapy (n = 5013) was the most common bridging strategy, followed by intra-aortic balloon pump (IABP; n = 2816), catheter-based temporary mechanical circulatory support (TMCS; n = 417), and veno-arterial extracorporeal membrane oxygenation (VA-ECMO; n = 465). Mortality was highest in patients bridged with VA-ECMO (22%), followed by catheter-based TMCS (10%), IABP (9%), and medical therapy (7%). Adverse post-operative outcomes were more frequent in LVAD recipients compared with HTx recipients. CONCLUSION: Among patients with ADHF-CS bridged to HTx or durable LVAD, the highest rates of death and adverse events during index hospitalization were observed in those bridged with VA-ECMO, followed by catheter-based TMCS, IABP, and medical therapy. Patients who received durable LVAD had higher rates of post-operative complications compared with HTx recipients. Prospective trials are needed to define optimal bridging strategies in patients with ADHF-CS.

Single-Cell Multiomics Reveals Clonal T-Cell Expansions and Exhaustion in Blastic Plasmacytoid Dendritic Cell Neoplasm.

The immune system represents a major barrier to cancer progression, driving the evolution of immunoregulatory interactions between malignant cells and T-cells in the tumor environment. Blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare acute leukemia with plasmacytoid dendritic cell (pDC) differentiation, provides a unique opportunity to study these interactions. pDCs are key producers of interferon alpha (IFNA) that play an important role in T-cell activation at the interface between the innate and adaptive immune system. To assess how uncontrolled proliferation of malignant BPDCN cells affects the tumor environment, we catalog immune cell heterogeneity in the bone marrow (BM) of five healthy controls and five BPDCN patients by analyzing 52,803 single-cell transcriptomes, including 18,779 T-cells. We test computational techniques for robust cell type classification and find that T-cells in BPDCN patients consistently upregulate interferon alpha (IFNA) response and downregulate tumor necrosis factor alpha (TNFA) pathways. Integrating transcriptional data with T-cell receptor sequencing via shared barcodes reveals significant T-cell exhaustion in BPDCN that is positively correlated with T-cell clonotype expansion. By highlighting new mechanisms of T-cell exhaustion and immune evasion in BPDCN, our results demonstrate the value of single-cell multiomics to understand immune cell interactions in the tumor environment.

The impact of hospital size on national trends and outcomes in isolated open proximal aortic surgery.

OBJECTIVE: To determine the impact of hospital size on national trend estimates of isolated open proximal aortic surgery for benchmarking hospital performance. METHODS: Patients age >18 years who underwent isolated open proximal aortic surgery for aneurysm and dissection from 2002 to 2014 were identified using the National Inpatient Sample. Concomitant valvular, vessel revascularization, re-do procedures, endovascular, and surgery for descending and thoracoabdominal aorta were excluded. Discharges were stratified by hospital size and analyzed using trend, multivariable regression, propensity-score matching analysis. RESULTS: Over a 13-year period, 53,657 isolated open proximal aortic operations were performed nationally. Although the total number of operations/year increased (∼2.9%/year increase) and overall in-hospital mortality decreased (∼4%/year; both P < .001 for trend), these did not differ by hospital size (P > .05). Large hospitals treated more sicker and older patients but had shorter length of stay and lower hospital costs (both P < .001). Even after propensity-score matching, large hospital continued to demonstrate superior in-hospital outcomes, although only statistically for major in-hospital cardiac complications compared with non-large hospitals. In our subgroup analysis of dissection versus non-dissection cohort, in-hospital mortality trends decreased only in the non-dissection cohort (P < .01) versus dissection cohort (P = .39), driven primarily by the impact of large hospitals (P < .01). CONCLUSIONS: This study demonstrates increasing volume and improving outcomes of isolated open proximal aortic surgeries nationally over the last decade regardless of hospital bed size. Moreover, the resource allocation of sicker patients to larger hospital resulted shorter length of stay and hospital costs, while maintaining similar operative mortality to small- and medium-sized hospitals.

N-myc-interactor mediates microbiome induced epithelial to mesenchymal transition and is associated with chronic lung allograft dysfunction.

BACKGROUND: Recent evidence suggests a role for lung microbiome in occurrence of chronic lung allograft dysfunction (CLAD). However, the mechanisms linking the microbiome to CLAD are poorly delineated. We investigated a possible mechanism involved in microbial modulation of mucosal response leading to CLAD with the hypothesis that a Proteobacteria dominant lung microbiome would inhibit N-myc-interactor (NMI) expression and induce epithelial to mesenchymal transition (EMT). METHODS: Explant CLAD, non-CLAD, and healthy nontransplant lung tissue were collected, as well as bronchoalveolar lavage from 14 CLAD and matched non-CLAD subjects, which were followed by 16S rRNA amplicon sequencing and quantitative polymerase chain reaction (PCR) analysis. Pseudomonas aeruginosa (PsA) or PsA-lipopolysaccharide was cocultured with primary human bronchial epithelial cells (PBEC). Western blot analysis and quantitative reverse transcription (qRT) PCR was performed to evaluate NMI expression and EMT in explants and in PsA-exposed PBECs. These experiments were repeated after siRNA silencing and upregulation (plasmid vector) of EMT regulator NMI. RESULTS: 16S rRNA amplicon analyses revealed that CLAD patients have a higher abundance of phyla Proteobacteria and reduced abundance of the phyla Bacteroidetes. At the genera level, CLAD subjects had an increased abundance of genera Pseudomonas and reduced Prevotella. Human CLAD airway cells showed a downregulation of the N-myc-interactor gene and presence of EMT. Furthermore, exposure of human primary bronchial epithelial cells to PsA resulted in downregulation of NMI and induction of an EMT phenotype while NMI upregulation resulted in attenuation of this PsA-induced EMT response. CONCLUSIONS: CLAD is associated with increased bacterial biomass and a Proteobacteria enriched airway microbiome and EMT. Proteobacteria such as PsA induces EMT in human bronchial epithelial cells via NMI, demonstrating a newly uncovered mechanism by which the microbiome induces cellular metaplasia.

Long-term Outcomes of Aortic Valve Replacement With Aortic Homograft: 27 Years Experience.

BACKGROUND: Aortic homografts have been used in young patients requiring aortic valve replacement. Currently, these grafts are generally reserved for aortic valve endocarditis with or without root abscess; however, longitudinal data are lacking. Our aim was to assess the long-term safety and durability of homograft implantation. METHODS: All adult patients undergoing aortic homograft implantation at a single institution from 1992 to 2019 were included. Outcomes of interest included all-cause mortality and aortic valve reoperation, studied over a median follow-up duration of 19 years. RESULTS: In all, 252 patients with a mean age of 49 years were included. Infective endocarditis was the primary indication for surgery in 95 patients (38%). The endocarditis group, compared with the no-endocarditis group, had a higher prevalence of New York Heart Association class III-IV (56% vs 26%), chronic kidney disease (22% vs 1%), prior cardiac surgery (40% vs 10%), and emergency status (7% vs 0%; all P < .001). Operative mortality was higher among endocarditis patients (16% vs 0.6%, P < .001), which persisted after risk adjustment. Among patients who survived to discharge, however, there was no difference in long-term survival between the endocarditis group and no-endocarditis group. Overall survival and freedom from reoperation were 88.3% and 80% at 15 years and 87.2% and 78% at 25 years, respectively. Indications for reoperation included structural valve deterioration (83%), endocarditis (12%), and mitral valve disease (5%). Reoperative mortality occurred in 2 patients (4.9%). CONCLUSIONS: Aortic homografts are associated with good long-term survival and admissible freedom from reoperation. Operative mortality is high among patients with endocarditis; however, for those who survive to discharge, long-term survival and durability are the same as for patients without endocarditis.

Multimodality Curative Treatment of IIIA/T4 Lung Adenocarcinoma.

We present a 41-year-old female smoker with concurrent invasive ductal carcinoma of the right breast and stage IIIA (T4N0M0) adenocarcinoma of the left lung requiring neoadjuvant chemoradiation followed by left pneumonectomy. We use this report as an educational work to show how multidisciplinary clinical decisions can be made to give way to successful treatment of a highly complex lung adenocarcinoma. Specifically, we show curative radical treatment of T4 disease and successful radical intervention of radiation-induced cardiac complications to achieve a comprehensive and curative treatment.

COVID-19 patient bridged to recovery with veno-venous extracorporeal membrane oxygenation.

BACKGROUND: In severe cases, the coronavirus disease 2019 (COVID-19) viral pathogen produces hypoxic respiratory failure unable to be adequately supported by mechanical ventilation. The role of extracorporeal membrane oxygenation (ECMO) remains unknown, with the few publications to date lacking detailed patient information or management algorithms all while reporting excessive mortality. METHODS: Case report from a prospectively maintained institutional ECMO database for COVID-19. RESULTS: We describe veno-venous (VV) ECMO in a COVID-19-positive woman with hypoxic respiratory dysfunction failing mechanical ventilation support while prone and receiving inhaled pulmonary vasodilator therapy. After 9 days of complex management secondary to her hyperdynamic circulation, ECMO support was successfully weaned to supine mechanical ventilation and the patient was ultimately discharged from the hospital. CONCLUSIONS: With proper patient selection and careful attention to hemodynamic management, ECMO remains a reasonable treatment option for patients with COVID-19.

Left ventricle unloading strategies in ECMO: A single-center experience.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is a life-saving technology capable of restoring perfusion but is not without significant complications that limit its realizable therapeutic benefit. ECMO-induced hemodynamics increase cardiac afterload risking left ventricular distention and impaired cardiac recovery. To mitigate potentially harmful effects, multiple strategies to unload the left ventricle (LV) are used in clinical practice but data supporting the optimal approach is presently lacking. MATERIALS & METHODS: We reviewed outcomes of our ECMO population from September 2015 through January 2019 to determine if our LV unloading strategies were associated with patient outcomes. We compared reactive (Group 1, n = 30) versus immediate (Group 2, n = 33) LV unloading and then compared patients unloaded with an Impella CP (n = 19) versus an intra-aortic balloon pump (IABP, n = 16), analyzing survival and ECMO-related complications. RESULTS: Survival was similar between Groups 1 and 2 (33 vs 42%, P = .426) with Group 2 experiencing more clinically-significant hemorrhage (40 vs. 67%, P = .034). Survival and ECMO-related complications were similar between patients unloaded with an Impella versus an IABP. However, the Impella group exhibited a higher rate of survival (37%) than predicted by their median SAVE score (18%). DISCUSSION: Based on this analysis, reactive unloading appears to be a viable strategy while venting with the Impella CP provides better than anticipated survival. Our findings correlate with recent large cohort studies and motivate further work to design clinical guidelines and future trial design.

The impact of hepatitis C viremic donor lung allograft characteristics on post-transplantation outcomes.

BACKGROUND: There is a low utilization rate of donated donor lungs. Historically, transplantation of lungs from hepatitis C-viremic donors to hepatitis C (HCV) negative recipients was avoided due to concern for worse graft survival. In the past few years with the advent of direct acting antiviral (DAA) therapy, there are emerging data suggesting the safety and efficacy of transplanting thoracic organs from HCV-viremic donors. This study assessed the differences in donor characteristics and allograft-specific clinical features at the time of organ offer and investigated whether these variables differed in HCV-viremic versus HCV-negative donors and impacted recipient outcomes. METHODS: We conducted a single-center, retrospective cohort study of adult patients who underwent a lung transplant at Brigham and Women's Hospital between March 2017 and October 2018. Patients were stratified based on their donor HCV status (HCV-viremic versus HCV-negative). Donor and allograft-specific characteristics and clinical features including chest imaging and bronchoscopy reports, respiratory cultures, and the donor's oxygenation as measured by the arterial partial pressure of oxygen (PaO2) were collected as well as recipient baseline characteristics and transplant outcomes. RESULTS: During the study period, 42 and 57 lung transplants were performed from HCV-viremic and HCV-negative donors, respectively. Donor age was similar in both cohorts. More HCV-viremic donors died from drug intoxication (71% versus 19%, P=0.0001) and had a history of cigarette use (83% versus 5%, P=0.0001) and drug use (76% versus 49%, P=0.007). There were differences in the baseline recipient characteristics including a lower median lung allocation score in the HCV-viremic cohort. The organ-specific clinical characteristics including the terminal PaO2, chest imaging and bronchoscopy findings, and evidence of pulmonary infection were similar between the two cohorts. The recipient outcomes overall were excellent and did not differ significantly in both cohorts in terms of graft and patient survival at 6 and 12 months. CONCLUSIONS: Despite a greater proportion of HCV-viremic donors being increased risk with a history of drug and cigarette use and having died as a result of drug intoxication, the quality of the HCV-viremic donor organs did not differ from the HCV-negative donor organs or impact graft and recipient survival. Due to an increasing number of transplants from increased risk donors and in order to develop safe and effective protocols to perform lung transplants from HCV-infected donors, further characterization of the donor and allograft-specific clinical features and longer-term recipient outcomes is greatly needed.

Sternotomy versus thoracotomy lung transplantation: key tips and contemporary results.

The purpose of this report is to provide an updated description of the technique of bilateral sequential lung transplant via median sternotomy. A sternotomy provides the advantage of less morbidity than the clamshell incision, as well as exposure to perform mechanical circulatory support and concurrent cardiac procedures. Our experience shows that lung transplantation via a midline sternotomy can be done with equivalent to better short-term outcomes than a clamshell incision, including earlier extubation and fewer transfusions. Familiarity with this technique is important for all surgeons managing end-stage lung disease.

Recipient Airway Bronchoplasty for Donor "Pig Bronchus".

Dissemination of surgical techniques to manage rare donor airway anomalies may improve outcomes after lung transplantation. This report describes a case of an unsuspected donor tracheal bronchus that was successfully managed with a native right mainstem bronchoplasty.

Comparison of heart transplant outcomes between recipients with pulsatile- vs continuous-flow LVAD.

OBJECTIVE: Continuous-flow (CF) left ventricular assist devices (LVADs) have replaced pulsatile flow (PF) LVADs irrespective of concerns from the physiologic changes/morbidity secondary to lack of pulsatility. Data comparing posttransplant outcomes in patients with CF vs PF LVADs are limited and conflicting. We used the Organ Procurement and Transplant Network database to compare posttransplant outcomes between CF and PF LVAD patients. METHODS: From 1 January 2005 to 31 December 2011, 3449 adult patients underwent primary heart alone transplantation. The cohort was restricted to 2741 recipients with LVAD at the time of transplant and divided into two groups: PF (Heartmate XVE) (n = 705) and CF (Heartmate II, HeartWare HVAD, and Jarvik 2000) (n = 2036). Endpoints were 30-day freedom from graft failure, 1-, and 5-year patient survival. Propensity score matching identified 705 pairs for adjusted comparisons. RESULTS: Among propensity-matched patients, 30-day freedom from graft failure after heart transplantation (PF = 94.8% vs CF = 95.2%, P > .7), and 1-, and 5-year patient survival (PF; 87.5% vs CF; 88.9%, P = .4, and PF;75.7% vs CF;77.5%, P = .3) were not different. CONCLUSION: Survival and freedom from graft failure after heart transplantation is similar between CF and PF LVADs. These findings are relevant as the use of CF devices increases despite physiologic changes related to the absence of pulsatility.

Mechanical Versus Bioprosthetic Aortic Valve Replacement in Patients Aged 50 Years and Younger.

BACKGROUND: This study evaluated outcomes in younger patients, specifically aged 50 years and younger, after mechanical aortic valve replacement (mAVR) and bioprosthetic AVR (bAVR). METHODS: From 1994 to 2016, 643 patients underwent AVR (411 mAVR and 232 bAVR) at age 50 or younger. Concomitant coronary artery bypass grafting and mitral valve procedures were also included. Propensity score-matching methods resulted in 170 evenly matched patient pairs. Primary end points were operative mortality and long-term survival. Secondary end points were stroke, major bleeding, and redo AVR. Median observation time was 8.1 years (range, 0 to 23.6 years). RESULTS: Overall, mean age was 41.9 years, and 29.3% were women, with an increasing trend toward use of bAVR. Mean age in the matched patients was 43.3 years for both cohorts (p = 0.68). Operative mortality, stroke, atrial fibrillation, reoperation for bleeding, and readmission rates within 30 days were all similar between the two groups. bAVR patients were at higher risk for redo AVR (13% vs 1.6%, p < 0.001), and mAVR patients were at higher risk for major bleeding events (8.5% vs 2.2%, p = 0.006). However, when adjusted, there were no differences in midterm and long-term survival between unmatched and matched cohorts. CONCLUSIONS: The increased risk of reoperation for bAVR and major bleeding incidents for mAVR was not reflected in midterm and long-term survival differences between the two groups. Our results suggest that bAVR may be an acceptable prosthesis choice for some patients aged 50 years and younger, although the results should be taken with caution.

Recurrence of Pericardial Mesothelioma Affecting the Myocardium After Pericardial Resection.

Primary pericardial mesothelioma represents less than 1% of all malignant mesotheliomas. These tumors are very rare, difficult to diagnose, and have a poor response to established treatments. Common clinical presentations include constrictive symptoms, cardiac tamponade, and cardiac failure. Surgical resection can be curative in early stages and for localized tumors, and pericardiectomy and chemotherapy are often used as palliative approaches. We present the case of a 54-year-old woman who has so far survived 4 years after a primary resection of a pericardial mesothelioma and was referred with myocardial and aortopulmonary window recurrences for further treatment.

Posttransplant Lymphoproliferative Disorders in Epstein-Barr Virus Donor Positive/Recipient Negative Lung Transplant Recipients.

BACKGROUND: Epstein-Barr virus (EBV) donor positive/recipient negative (D+/R-) status is a significant risk factor for posttransplant lymphoproliferative disorder (PTLD) in lung transplant. There are, however, no studies that identify the risk factors for PTLD in the EBV D+/R- lung transplant population to guide the decision to proceed with an EBV-positive donor. METHODS: This was a retrospective cohort study of adults listed in the Scientific Registry of Transplant Recipients between May 5, 2005, and August 31, 2016. Cox proportional hazards models were used to assess the impact of EBV D+/R- status on the development of PTLD, the impact of PTLD on survival, and survival differences between EBV D+/R- and EBV D-/R- recipients. RESULTS: The incidence of PTLD was 6.2% (79 of 1,281) versus 1.4% (145 of 10,352) in EBV D+/R- versus all other recipients (adjusted odds ratio 4.0; 95% confidence interval: 2.8 to 5.9, p < 0.001). Among EBV D+/R- recipients, age less than 40 years and white race were associated with PTLD. The EBV D+/R- patients who had PTLD had increased adjusted risk of death (hazard ratio 1.91; 95% confidence interval: 1.35 to 2.71; p < 0.001). Compared with EBV D+/R- recipients, EBV D-/R- recipients did not have improved adjusted survival (hazard ratio 0.82; 95% confidence interval: 0.57 to 1.18; p = 0.30). CONCLUSIONS: Despite increased rates of PTLD and associated mortality in the EBV D+/R- population, EBV seronegative patients did not have worse mortality when transplanted with lungs from EBV seropositive donors compared with lungs from EBV seronegative donors. Consideration should be given for close monitoring for PTLD among EBV D+/R- recipients, particularly those who are white and less than 40 years of age.

Impact of concomitant mitral valve repair for severe mitral regurgitation at the time of continuous-flow left ventricular assist device insertion.

OBJECTIVES: Mitral regurgitation (MR) is common in patients with end-stage heart failure. We assessed the effect of performing concomitant mitral valve repair during continuous-flow left ventricular assist device (CF-LVAD) implantation in patients with severe preoperative MR. METHODS: We performed a single-centre, retrospective review of all patients who underwent CF-LVAD implantation between December 1999 and December 2013 (n = 469). Patients with severe preoperative MR (n = 78) were identified and then stratified according to whether they underwent concomitant valve repair. Univariate and survival analyses were performed, and multivariable regression was used to determine predictors of survival. RESULTS: Of the 78 patients with severe MR, 21 underwent valve repair at the time of CF-LVAD implantation (repair group) and 57 did not (non-repair group). A comparison of the 2 groups showed significant differences between groups: INTERMACS I 16.985 vs 9.52%, (P = 0.039), cardiopulmonary bypass time 82.09 vs 109.4 min (P = 0.0042) and the use of HeartMate II 63.16 vs 100% (P = 0.001). Survival analysis suggested trends towards improved survival and a lower incidence of heart failure-related readmissions in the repair group. Multivariable regression analysis showed no significant independent predictors of survival (mitral valve repair: odds ratio 0.4, 95% confidence interval 0.8-1.5; P = 0.2). CONCLUSIONS: Despite the lack of statistical significance, trends towards improved survival and a lower incidence of heart failure events suggest that mitral valve repair may be beneficial in patients undergoing CF-LVAD implantation. Given the known relationship between severe MR and mortality, further study is encouraged to confirm the value of mitral valve repair in these patients.

Pacemaker Use Following Heart Transplantation.

BACKGROUND: The incidence of permanent pacemaker implantation after orthotopic heart transplantation has been reported to be 2%-24%. Transplanted hearts usually exhibit sinus rhythm in the operating room following reperfusion, and most patients do not exhibit significant arrhythmias during the postoperative period. However, among the patients who do exhibit abnormalities, pacemakers may be implanted for early sinus node dysfunction but are rarely used after 6 months. Permanent pacing is often required for atrioventricular block. A different cohort of transplant patients presents later with bradycardia requiring pacemaker implantation, reported to occur in approximately 1.5% of patients. The objectives of this study were to investigate the indications for pacemaker implantation, compare the need for pacemakers following bicaval vs biatrial anastomosis, and examine the long-term outcomes of heart transplant patients who received pacemakers. METHODS: For this retrospective, case-cohort, single-institution study, patients were identified from clinical research and administrative transplant databases. Information was supplemented with review of the medical records. Standard statistical techniques were used, with chi-square testing for categorical variables and the 2-tailed t test for continuous variables. Survival was compared with the use of log-rank methods. RESULTS: Between January 1968 and February 2008, 1,450 heart transplants were performed at Stanford University. Eighty-four patients (5.8%) were identified as having had a pacemaker implanted. Of these patients, 65.5% (55) had the device implanted within 30 days of transplantation, and 34.5% (29) had late implantation. The mean survival of patients who had an early pacemaker implant was 6.4 years compared to 7.7 years for those with a late pacemaker implant (P<0.05). Sinus node dysfunction and heart block were the most common indications for pacemaker implantation. Starting in 1997, a bicaval technique was used for implantation. The incidence of pacemaker implantation by technique was 2.0% for bicaval and 9.1% for biatrial (P=0.001). Significantly more rejection episodes occurred in the pacemaker group (2.67 ± 2.18) compared with the no-pacemaker group (2.01 ± 2.05) (P<0.05). CONCLUSION: Our results show a decreased pacemaker need after bicaval anastomosis and that more patients who needed a pacemaker after transplantation had a pretransplant diagnosis of ischemic cardiomyopathy. In our cohort, the need for a permanent pacemaker was also associated with older donor grafts and an increase in the number of treated rejection episodes.