Multicenter evaluation of left ventricular assist device implantation with or without ECMO bridge in cardiogenic shock.

BACKGROUND: The efficacy of extracorporeal membrane oxygenation (ECMO) as a bridge to left ventricular assist device (LVAD) remains unclear, and recipients of the more contemporary HeartMate 3 (HM3) LVAD are not well represented in previous studies. We therefore undertook a multicenter, retrospective study of this population. METHODS AND RESULTS: INTERMACS 1 LVAD recipients from five U.S. centers were included. In-hospital and one-year outcomes were recorded. The primary outcome was the overall mortality hazard comparing ECMO versus non-ECMO patients by propensity-weighted survival analysis. Secondary outcomes included survival by LVAD type, as well as postoperative and one-year outcomes. One hundred and twenty-seven patients were included; 24 received ECMO as a bridge to LVAD. Mortality was higher in patients bridged with ECMO in the primary analysis (HR 3.22 [95%CI 1.06-9.77], p = 0.039). Right ventricular assist device was more common in the ECMO group (ECMO: 54.2% vs non-ECMO: 11.7%, p < 0.001). Ischemic stroke was higher at one year in the ECMO group (ECMO: 25.0% vs non-ECMO: 4.9%, p = 0.006). Among the study cohort, one-year mortality was lower in HM3 than in HeartMate II (HMII) or HeartWare HVAD (10.5% vs 46.9% vs 31.6%, respectively; p < 0.001) recipients. Pump thrombosis at one year was lower in HM3 than in HMII or HVAD (1.8% vs 16.1% vs 16.2%, respectively; p = 0.026) recipients. CONCLUSIONS: Higher mortality was observed with ECMO as a bridge to LVAD, likely due to higher acuity illness, yet acceptable one-year survival was seen compared with historical rates. The receipt of the HM3 was associated with improved survival compared with older generation devices.

Deciphering cell states and genealogies of human haematopoiesis.

The human blood system is maintained through the differentiation and massive amplification of a limited number of long-lived haematopoietic stem cells (HSCs)1. Perturbations to this process underlie diverse diseases, but the clonal contributions to human haematopoiesis and how this changes with age remain incompletely understood. Although recent insights have emerged from barcoding studies in model systems2-5, simultaneous detection of cell states and phylogenies from natural barcodes in humans remains challenging. Here we introduce an improved, single-cell lineage-tracing system based on deep detection of naturally occurring mitochondrial DNA mutations with simultaneous readout of transcriptional states and chromatin accessibility. We use this system to define the clonal architecture of HSCs and map the physiological state and output of clones. We uncover functional heterogeneity in HSC clones, which is stable over months and manifests as both differences in total HSC output and biases towards the production of different mature cell types. We also find that the diversity of HSC clones decreases markedly with age, leading to an oligoclonal structure with multiple distinct clonal expansions. Our study thus provides a clonally resolved and cell-state-aware atlas of human haematopoiesis at single-cell resolution, showing an unappreciated functional diversity of human HSC clones and, more broadly, paving the way for refined studies of clonal dynamics across a range of tissues in human health and disease.

Limited Effect of Prevention Strategies on Incidence of Clinically Detectable Venous Thromboembolism After Lung Transplantation.

BACKGROUND: Thromboembolic complications are common post-lung transplant, leading to significant morbidity. We instituted multiple interventions because of an observed 36.8% incidence of venous thromboembolism (VTE) (Incidence rate (IR) 5.74/1000 pt days) in our recipients. METHODS: Our initiative commenced January 2015 with enoxaparin initiation within 6-8 hours of intensive care unit arrival and continuation for 4-6 weeks. We evaluated the IR of VTE in lung transplant recipients within 90 days of transplant. In 2017, the protocol was modified to extend the time to initiation of prophylaxis to within 72 hours of ICU arrival. In 2019, we further amended our intraoperative vascular access strategy. RESULTS: Eighteen of 26 lung transplant recipients (LTR) met inclusion criteria in the 2015 cohort. Six of 18 (33.3%) developed VTE, 50% of which were upper extremity (UE), line associated. Fifty two of 75 LTR were eligible for enoxaparin prophylaxis in the 2017 cohort. Fifteen of 52 subjects (28.8%) developed VTE, 77.8% of which were UE and line associated. Despite improved adherence in 2017, there was little change in VTE IR (3.90/1000 pt days compared with 3.85/1000 pt days). Twenty six of 43 LTR met protocol inclusion criteria in the 2019 cohort. Ten subjects (38.5%) developed VTE, 67% of which were UE and line associated (IR 5.18/1000 pt days). CONCLUSION: Our prospective study found that LTR remain at high risk for VTE despite aggressive prophylaxis with 4-6 weeks of enoxaparin and adjustment of vascular access approach. Alternative interventions should be investigated to minimize VTE development in this vulnerable population.

Transplantation Outcomes with Donor Hearts after Circulatory Death.

BACKGROUND: Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited. METHODS: We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation. RESULTS: A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation. CONCLUSIONS: In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.).

Adverse Outcomes Associated With Atrial Arrhythmias After Veno-Venous Extracorporeal Membrane Oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) is used as a treatment modality in those who fail to respond to conventional care. Hypoxia and medications used in the intensive care unit may increase risk for atrial arrhythmias (AA). This study aims to evaluate the impact of AA on post-VV ECMO outcome. A retrospective review of patients who were placed on VV ECMO between October 2016 and October 2021. One hundred forty-five patients were divided into two groups, AA and no AA. Baseline characteristic and potential risk factors were assessed. Uni- and multivariate analysis using logistic regression models were constructed to evaluate the predictors of mortality between groups. Survival between groups was estimated by the Kaplan-Meier method using the log-rank test. Advanced age with history of coronary artery disease and hypertension were associated with increased risk to develop AA post-VV ECMO placement ( p value < 0.05). Length on ECMO, time intubated, hospital length of stay, and sepsis were significantly increased in patients in the AA group ( p value < 0.05). There was no difference in the overall mortality between the two groups. AAs were associated with worse hospital course and complications but no difference in overall mortality rate. Age and cardiovascular disease seem to be predisposing risk factors for this. Further studies are needed to investigate potential strategies to prevent AAs development in this population.

IL-33 mediates Pseudomonas induced airway fibrogenesis and is associated with CLAD.

BACKGROUND: Long term outcomes of lung transplantation are impacted by the occurrence of chronic lung allograft dysfunction (CLAD). Recent evidence suggests a role for the lung microbiome in the occurrence of CLAD, but the exact mechanisms are not well defined. We hypothesize that the lung microbiome inhibits epithelial autophagic clearance of pro-fibrotic proteins in an IL-33 dependent manner, thereby augmenting fibrogenesis and risk for CLAD. METHODS: Autopsy derived CLAD and non-CLAD lungs were collected. IL-33, P62 and LC3 immunofluorescence was performed and assessed using confocal microscopy. Pseudomonas aeruginosa (PsA), Streptococcus Pneumoniae (SP), Prevotella Melaninogenica (PM), recombinant IL-33 or PsA-lipopolysaccharide was co-cultured with primary human bronchial epithelial cells (PBEC) and lung fibroblasts in the presence or absence of IL-33 blockade. Western blot analysis and quantitative reverse transcription (qRT) PCR was performed to evaluate IL-33 expression, autophagy, cytokines and fibroblast differentiation markers. These experiments were repeated after siRNA silencing and upregulation (plasmid vector) of Beclin-1. RESULTS: Human CLAD lungs demonstrated markedly increased expression of IL-33 and reduced basal autophagy compared to non-CLAD lungs. Exposure of co-cultured PBECs to PsA, SP induced IL-33, and inhibited PBEC autophagy, while PM elicited no significant response. Further, PsA exposure increased myofibroblast differentiation and collagen formation. IL-33 blockade in these co-cultures recovered Beclin-1, cellular autophagy and attenuated myofibroblast activation in a Beclin-1 dependent manner. CONCLUSION: CLAD is associated with increased airway IL-33 expression and reduced basal autophagy. PsA induces a fibrogenic response by inhibiting airway epithelial autophagy in an IL-33 dependent manner.

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.

The Cost-effectiveness of Transplanting Hearts From Hepatitis C-infected Donors Into Uninfected Recipients.

BACKGROUND: The DONATE HCV trial demonstrated the safety and efficacy of transplanting hearts from hepatitis C viremic (HCV+) donors. In this report, we examine the cost-effectiveness and impact of universal HCV+ heart donor eligibility in the United States on transplant waitlist time and life expectancy. METHODS: We developed a microsimulation model to compare 2 waitlist strategies for heart transplant candidates in 2018: (1) status quo (SQ) and (2) SQ plus HCV+ donors (SQ + HCV). From the DONATE HCV trial and published national datasets, we modeled mean age (53 years), male sex (75%), probabilities of waitlist mortality (0.01-0.10/month) and transplant (0.03-0.21/month) stratified by medical urgency, and posttransplant mortality (0.003-0.052/month). We assumed a 23% increase in transplant volume with SQ + HCV compared with SQ. Costs (2018 United States dollar) included waitlist care ($2200-190 000/month), transplant ($213 400), 4-wk HCV treatment ($26 000), and posttransplant care ($2500-11 300/month). We projected waitlist time, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs [$/QALY, discounted 3%/year]; threshold ≤$100 000/QALY). RESULTS: Compared with SQ, SQ + HCV decreased waitlist time from 8.7 to 6.7 months, increased undiscounted life expectancy from 8.9 to 9.2 QALYs, and increased discounted lifetime costs from $671 400/person to $690 000/person. Four-week HCV treatment comprised 0.5% of lifetime costs. The ICER of SQ + HCV compared with SQ was $74 100/QALY and remained ≤$100 000/QALY with up to 30% increases in transplant and posttransplant costs. CONCLUSIONS: Transplanting hearts from HCV-infected donors could decrease waitlist times, increase life expectancy, and be cost-effective. These findings were robust within the context of current high HCV treatment costs.

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.

Enhanced Recovery After Cardiac Surgery: A Propensity-Matched Analysis.

Enhanced Recovery After Surgery (ERAS) pathways have improved clinical outcomes, cost-effectiveness, and patient satisfaction across multiple non-cardiac surgical specialties. Since the adaptation of ERAS in cardiac surgery is rapidly increasing yet still evolving, herein, we demonstrate early results of our implementation of ERAS cardiac guidelines. We retrospectively reviewed all patients who were managed with our institutional ERAS Cardiac Surgery guidelines between 5/2018 and 6/2019(N = 102). Postoperative primary outcomes (total ventilation times(hours), intensive-care unit(ICU) stay, and postoperative hospital length of stay (LOS)) were compared to 1:1 propensity matched controls from the pre ERAS era between January 2017 and March 2019. A total of 76 propensity-matched pairs were identified. Compared to the matched controls, ERAS patients had significantly shorter median ventilation times(3.5 vs. 5.3 hours, p = .01), ICU stays(median 28 vs 48 hours, p=.005) and postoperative hospital LOS (median 5 vs. 6 days, p = .03). There were no operative mortalities and no significant differences in 30-day readmission rates. There were also no significant differences in post-operative stroke, acute kidney injury, atrial fibrillation, and reoperation rates for bleeding. Two-year survival was also not statistically different between the two cohorts (p = .22). Our initial experience with implementation of ERAS protocols in cardiac surgery appear to demonstrate that these protocols are associated with shorter ventilation times, ICU stay, and hospital LOS without compromising patient outcomes. While these results are promising yet preliminary, further studies are warranted to demonstrate whether ERAS algorithms in cardiac surgery can consistently expedite postoperative recovery and improve outcomes.

All-cause Readmission after Transcatheter Aortic Valve Replacement in a Community Hospital - Long Term Follow-up.

BACKGROUND: Post-procedure readmissions are associated with lower quality of life and increased economic burden. The study aimed to identify predictors for long-term all-cause readmissions in patients who underwent transcatheter aortic valve replacement (TAVR) in a community hospital. METHODS: A Historical cohort study of all adults who underwent TAVR at Cape-Cod hospital between June 2015 and December 2017 was performed and data on readmissions was collected up-to May 2020 (median follow up of 3.3 years). Pre-procedure, procedure and in-hospital post-procedure parameters were collected. Readmission rate was evaluated, and univariate and multivariable analyses were applied to identify predictors for readmission. RESULTS: The study included 262 patients (mean age 83.7±7.9 years, 59.9% males). The median Society of Thoracic Surgeons (STS) probability of mortality (PROM) score was 4.9 (IQR, 3.1-7.9). Overall, 120 patients were readmitted. Ten percent were readmitted within 1-month, 20.8% within 3-months, 32.0% within 6-months and 44.5% within 1-year. New readmissions after 1-year were rare. STS PROM 5% or above (HR 1.50, p = 0.039), pre-procedure anemia (HR 1.63, p = 0.034), severely decreased pre-procedure renal function (HR 1.93, p = 0.040) and procedural complication (HR 1.65, p = 0.013) were independent predictors for all-cause readmission. CONCLUSIONS: Elevated procedural risk, anemia, renal dysfunction and procedural complication are important predictors for readmission. Pre-procedure and ongoing treatment of the patient's background diseases and completion of treatment for complications prior to discharge may contribute to a reduction in the rate of readmissions.

1-year outcomes for lung transplantation recipients with non-alcoholic fatty liver disease.

Advanced hepatic fibrosis and cirrhosis are absolute contraindications to lung transplantation. [ 1] However, whether fatty liver disease with mild-moderate fibrosis contributes to increased adverse outcomes post-lung transplantation remains unknown. We present a retrospective analysis of patients transplanted at Brigham and Women's Hospital between 2015 and 2017 to identify whether patients with mild-moderate non-alcoholic fatty liver disease (NAFLD) experience increased short-term complications compared to patients with normal liver architecture. Patients with advanced (F3-F4) fibrosis and/or cirrhosis were considered non-suitable transplant candidates, a priori. This study was powered for a difference in index hospital-free days within the first 30 days of 25% (α=0.05, ß=0.8). Secondary outcomes included index intensive care unit (ICU)-free days within the first 10 days post-transplant, perioperative blood product transfusion, incidence of index hospitalisation arrhythmias and delirium, need for insulin on discharge post-transplant, tacrolimus dose required to maintain a trough of 8-12 ng·mL-1 at index hospital discharge, and 1-year post-transplant incidence of insulin-dependent diabetes, acute kidney injury, acute cellular rejection, unplanned hospital readmissions and infection. 150 patients underwent lung transplantation between 2015 and 2017 and were included in the analysis; of these patients 40 (27%) had evidence of NAFLD. Median index hospital-free days for patients with NAFLD were non-inferior to those without (16 days, IQR 10.5-19.5 versus 12 days, IQR 0-18.0, p=0.03). Regarding secondary outcomes, both index hospitalisation and 1-year outcomes were non-inferior between patients with NAFLD and those with normal liver architecture. This study demonstrates that mild-moderate severity NAFLD may not be a contraindication to lung transplantation.

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.

Advanced Surgical and Percutaneous Approaches to Pulmonary Vascular Disease.

Despite progress in modern medical therapy, pulmonary hypertension remains an unremitting disease. Once severe or refractory to medical therapy, advanced percutaneous and surgical interventions can palliate right ventricular overload, bridge to transplantation, and overall extend a patient's course. These approaches include atrial septostomy, Potts shunt, and extracorporeal life support. Bilateral lung transplantation is the ultimate treatment for eligible patients, although the need for suitable lungs continues to outpace availability. Measures such as ex vivo lung perfusion are ongoing to expand donor lung availability, increase rates of transplant, and decrease waitlist mortality.

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.

Joint preoperative transthoracic and intraoperative transoesophageal echocardiographic assessment of functional mitral regurgitation severity provides better association with long-term mortality.

OBJECTIVES: Functional mitral regurgitation (MR) is observed with ischaemic heart disease or aortic valve disease. Assessing the value of mitral valve repair or replacement (MVR/P) is complicated by frequent discordance between preoperative transthoracic echocardiographic (pTTE) and intraoperative transoesophageal echocardiographic (iTOE) assessment of MR severity. We examined the association of pTTE and iTOE with postoperative mortality in patients with or without MR, at the time of coronary artery bypass grafting (CABG) and/or aortic valve replacement without MVR/P. METHODS: Medical records of 6629 patients undergoing CABG and/or aortic valve replacement surgery with or without functional MR and who did not undergo MVR/P were reviewed. MR severity assessed by pTTE and iTOE were examined for association with postoperative mortality using proportional hazards regression while accounting for patient and operative characteristics. RESULTS: In 72% of 709 patients with clinically significant (moderate or greater) functional MR detected by pTTE, iTOE performed after induction of anaesthesia demonstrated a reduction in MR severity, while 2% of patients had increased severity of MR by iTOE. iTOE assessment of MR was better associated with long-term postoperative mortality than pTTE in patients with moderate MR [hazard ratio (HR) 1.31 (1.11-1.55) vs 1.02 (0.89-1.17), P-value for comparison of HR 0.025] but was not different for more than moderate MR [1.43 (0.96-2.14) vs 1.27 (0.80-2.02)]. CONCLUSIONS: In patients undergoing CABG and/or aortic valve replacement without MVR/P, these findings support intraoperative reassessment of MR severity by iTOE as an adjunct to pTTE in the prediction of mortality. Alone, these findings do not yet provide evidence for an operative strategy.