Pericardial fluid troponin in cardiac surgery.

BACKGROUND AND OBJECTIVE: Pericardial Fluid (PF) is a rich reservoir of biologically active factors. Due to its proximity to the heart, the biochemical structure of PF may reflect the pathological changes in the cardiac interstitial environment. This manuscript aimed to determine whether the PF level of cardiac troponins changes in patients undergoing cardiac surgery. METHODS: This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline, EMBASE, Cochrane, ClinicalTrials.gov, and Google Scholar databases were electronically searched for primary studies using the keywords "pericardial fluid," "troponin," and "cardiac surgery." The primary outcome of interest was changes in troponin levels within the PF preoperatively and postoperatively. Secondary outcomes of interest included comparisons between troponin level changes in the PF compared to plasma. RESULTS: A total of 2901 manuscripts were screened through a title and abstract stage by two independent blinded reviewers. Of those, 2894 studies were excluded, and the remaining seven studies underwent a full-text review. Studies were excluded if they did not provide data or failed to meet inclusion criteria. Ultimately, six articles were included that discussed cardiac troponin levels within the PF in patients who had undergone cardiac surgery. Pericardial troponin concentration increased over time after surgery, and levels were significantly higher in PF compared to serum. All studies found that the type of operation did not affect these overall observations. CONCLUSION: Our review of the literature suggest that the PF level of cardiac troponins increases in patients undergoing cardiac surgery, irrespective of the procedure type. However, these changes' exact pattern and clinical significance remain undefined.

Temporal trends in mortality of aortic dissection and rupture in the UK, Japan, the USA and Canada.

OBJECTIVE: Aortic dissection and aortic aneurysm rupture are aortic emergencies and their clinical outcomes have improved over the past two decades; however, whether this has translated into lower mortality across countries remains an open question. The purpose of this study was to compare mortality trends from aortic dissection and rupture between the UK, Japan, the USA and Canada. METHODS: We analysed the WHO mortality database to determine trends in mortality from aortic dissection and rupture in four countries from 2000 to 2019. Age-standardised mortality rates per 100 000 persons were calculated, and annual percentage change was estimated using joinpoint regression. RESULTS: Age-standardised mortality rates per 100 000 persons from aortic dissection and rupture in 2019 were 1.04 and 1.80 in the UK, 2.66 and 1.16 in Japan, 0.76 and 0.52 in the USA, and 0.67 and 0.81 in Canada, respectively. There was significantly decreasing trends in age-standardised mortality from aortic rupture in all four countries and decreasing trends in age-standardised mortality from aortic dissection in the UK over the study period. There was significantly increasing trends in mortality from aortic dissection in Japan over the study period. Joinpoint regression identified significant changes in the aortic dissection trends from decreasing to increasing in the USA from 2010 and Canada from 2012. In sensitivity analyses stratified by sex, similar trends were observed. CONCLUSIONS: Trends in mortality from aortic rupture are decreasing; however, mortality from aortic dissection is increasing in Japan, the USA and Canada. Further study to explain these trends is warranted.

Phase I/Ib, open-label, multicenter, dose-escalation study of the anti-TGF-ß monoclonal antibody, NIS793, in combination with spartalizumab in adult patients with advanced tumors.

BACKGROUND: NIS793 is a human IgG2 monoclonal antibody that binds to transforming growth factor beta (TGF-ß). This first-in-human study investigated NIS793 plus spartalizumab treatment in patients with advanced solid tumors. METHODS: Patients received NIS793 (0.3-1 mg/kg every 3 weeks (Q3W)) monotherapy; following evaluation of two dose levels, dose escalation continued with NIS793 plus spartalizumab (NIS793 0.3-30 mg/kg Q3W and spartalizumab 300 mg Q3W or NIS793 20-30 mg/kg every 2 weeks [Q2W] and spartalizumab 400 mg every 4 weeks (Q4W)). In dose expansion, patients with non-small cell lung cancer (NSCLC) resistant to prior anti-programmed death ligand 1 or patients with microsatellite stable colorectal cancer (MSS-CRC) were treated at the recommended dose for expansion (RDE). RESULTS: Sixty patients were treated in dose escalation, 11 with NIS793 monotherapy and 49 with NIS793 plus spartalizumab, and 60 patients were treated in dose expansion (MSS-CRC: n=40; NSCLC: n=20). No dose-limiting toxicities were observed. The RDE was established as NIS793 30 mg/kg (2100 mg) and spartalizumab 300 mg Q3W. Overall 54 (49.5%) patients experienced ≥1 treatment-related adverse event, most commonly rash (n=16; 13.3%), pruritus (n=10; 8.3%), and fatigue (n=9; 7.5%). Three partial responses were reported: one in renal cell carcinoma (NIS793 30 mg/kg Q2W plus spartalizumab 400 mg Q4W), and two in the MSS-CRC expansion cohort. Biomarker data showed evidence of target engagement through increased TGF-ß/NIS793 complexes and depleted active TGF-ß in peripheral blood. Gene expression analyses in tumor biopsies demonstrated decreased TGF-ß target genes and signatures and increased immune signatures. CONCLUSIONS: In patients with advanced solid tumors, proof of mechanism of NIS793 is supported by evidence of target engagement and TGF-ß pathway inhibition. TRIAL REGISTRATION NUMBER: NCT02947165.

Transforming Growth Factor-ß Blockade in Pancreatic Cancer Enhances Sensitivity to Combination Chemotherapy.

BACKGROUND & AIMS: Transforming growth factor-b (TGFb) plays pleiotropic roles in pancreatic cancer, including promoting metastasis, attenuating CD8 T-cell activation, and enhancing myofibroblast differentiation and deposition of extracellular matrix. However, single-agent TGFb inhibition has shown limited efficacy against pancreatic cancer in mice or humans. METHODS: We evaluated the TGFß-blocking antibody NIS793 in combination with gemcitabine/nanoparticle (albumin-bound)-paclitaxel or FOLFIRINOX (folinic acid [FOL], 5-fluorouracil [F], irinotecan [IRI] and oxaliplatin [OX]) in orthotopic pancreatic cancer models. Single-cell RNA sequencing and immunofluorescence were used to evaluate changes in tumor cell state and the tumor microenvironment. RESULTS: Blockade of TGFß with chemotherapy reduced tumor burden in poorly immunogenic pancreatic cancer, without affecting the metastatic rate of cancer cells. Efficacy of combination therapy was not dependent on CD8 T cells, because response to TGFß blockade was preserved in CD8-depleted or recombination activating gene 2 (RAG2-/-) mice. TGFß blockade decreased total α-smooth muscle actin-positive fibroblasts but had minimal effect on fibroblast heterogeneity. Bulk RNA sequencing on tumor cells sorted ex vivo revealed that tumor cells treated with TGFß blockade adopted a classical lineage consistent with enhanced chemosensitivity, and immunofluorescence for cleaved caspase 3 confirmed that TGFß blockade increased chemotherapy-induced cell death in vivo. CONCLUSIONS: TGFß regulates pancreatic cancer cell plasticity between classical and basal cell states. TGFß blockade in orthotropic models of pancreatic cancer enhances sensitivity to chemotherapy by promoting a classical malignant cell state. This study provides scientific rationale for evaluation of NIS793 with FOLFIRINOX or gemcitabine/nanoparticle (albumin-bound) paclitaxel chemotherapy backbone in the clinical setting and supports the concept of manipulating cancer cell plasticity to increase the efficacy of combination therapy regimens.

Mortality trends of aortic stenosis in high-income countries from 2000 to 2020.

OBJECTIVE: The purpose of this study is to describe recent mortality trends from aortic stenosis (AS) among eight high-income countries. METHODS: We analysed the WHO mortality database to determine trends in mortality from AS in the UK, Germany, France, Italy, Japan, Australia, the USA and Canada from 2000 to 2020. Crude and age-standardised mortality rates per 100 000 persons were calculated. We calculated age-specific mortality rates in three groups (<64, 65-79 and ≥80 years). Annual percentage change was analysed using joinpoint regression. RESULTS: During the observation period, the crude mortality rates per 100 000 persons increased in all the eight countries (from 3.47 to 5.87 in the UK, from 2.98 to 8.93 in Germany, from 3.84 to 5.52 in France, from 1.97 to 4.33 in Italy, from 1.12 to 5.49 in Japan, from 2.14 to 3.38 in Australia, from 3.58 to 4.22 in the USA and from 2.12 to 5.00 in Canada). In joinpoint regression of age-standardised mortality rates, trend changes towards a decrease were observed in Germany after 2012 (-1.2%, p=0.015), Australia after 2011 (-1.9%, p=0.005) and the USA after 2014 (-3.1%, p<0.001). Age-specific mortality rates in age group ≥80 years had shifts towards decreasing trends in all the eight countries in contrast to other younger age groups. CONCLUSIONS: While crude mortality rates increased in the eight countries, shifts towards decreasing trends were identified in age-standardised mortality rates in three countries and in the elderly aged ≥80 years in the eight countries. Further multidimensional observation is warranted to clarify the mortality trends.

Targeting the IL1ß Pathway for Cancer Immunotherapy Remodels the Tumor Microenvironment and Enhances Antitumor Immune Responses.

High levels of IL1ß can result in chronic inflammation, which in turn can promote tumor growth and metastasis. Inhibition of IL1ß could therefore be a promising therapeutic option in the treatment of cancer. Here, the effects of IL1ß blockade induced by the mAbs canakinumab and gevokizumab were evaluated alone or in combination with docetaxel, anti-programmed cell death protein 1 (anti-PD-1), anti-VEGFα, and anti-TGFß treatment in syngeneic and humanized mouse models of cancers of different origin. Canakinumab and gevokizumab did not show notable efficacy as single-agent therapies; however, IL1ß blockade enhanced the effectiveness of docetaxel and anti-PD-1. Accompanying these effects, blockade of IL1ß alone or in combination induced significant remodeling of the tumor microenvironment (TME), with decreased numbers of immune suppressive cells and increased tumor infiltration by dendritic cells (DC) and effector T cells. Further investigation revealed that cancer-associated fibroblasts (CAF) were the cell type most affected by treatment with canakinumab or gevokizumab in terms of change in gene expression. IL1ß inhibition drove phenotypic changes in CAF populations, particularly those with the ability to influence immune cell recruitment. These results suggest that the observed remodeling of the TME following IL1ß blockade may stem from changes in CAF populations. Overall, the results presented here support the potential use of IL1ß inhibition in cancer treatment. Further exploration in ongoing clinical studies will help identify the best combination partners for different cancer types, cancer stages, and lines of treatment.

cIAP1/2 Antagonism Induces Antigen-Specific T Cell-Dependent Immunity.

Checkpoint blockade immunotherapy has failed in pancreatic cancer and other poorly responsive tumor types in part due to inadequate T cell priming. Naive T cells can receive costimulation not only via CD28 but also through TNF superfamily receptors that signal via NF-κB. Antagonists of the ubiquitin ligases cellular inhibitor of apoptosis protein (cIAP)1/2, also called second mitochondria-derived activator of caspases (SMAC) mimetics, induce degradation of cIAP1/2 proteins, allowing for the accumulation of NIK and constitutive, ligand-independent activation of alternate NF-κB signaling that mimics costimulation in T cells. In tumor cells, cIAP1/2 antagonists can increase TNF production and TNF-mediated apoptosis; however, pancreatic cancer cells are resistant to cytokine-mediated apoptosis, even in the presence of cIAP1/2 antagonism. Dendritic cell activation is enhanced by cIAP1/2 antagonism in vitro, and intratumoral dendritic cells show higher expression of MHC class II in tumors from cIAP1/2 antagonism-treated mice. In this study, we use in vivo mouse models of syngeneic pancreatic cancer that generate endogenous T cell responses ranging from moderate to poor. Across multiple models, cIAP1/2 antagonism has pleiotropic beneficial effects on antitumor immunity, including direct effects on tumor-specific T cells leading to overall increased activation, increased control of tumor growth in vivo, synergy with multiple immunotherapy modalities, and immunologic memory. In contrast to checkpoint blockade, cIAP1/2 antagonism does not increase intratumoral T cell frequencies. Furthermore, we confirm our previous findings that even poorly immunogenic tumors with a paucity of T cells can experience T cell-dependent antitumor immunity, and we provide transcriptional clues into how these rare T cells coordinate downstream immune responses.

Clinical impact of right ventricular pacing burden in patients with post-transcatheter aortic valve replacement permanent pacemaker implantation.

AIMS: Patients who undergo permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR) have a worse outcome. The aim of this study was to identify risk factors of worse outcomes in patients with post-TAVR PPM implantation. METHODS AND RESULTS: This is a single-centre, retrospective study of consecutive patients who underwent post-TAVR PPM implantation from 11 March 2011 to 9 November 2019. Clinical outcomes were evaluated by landmark analysis with cut-off at 1 year after the PPM implantation. Of the 1389 patients underwent TAVR during the study duration and a total of 110 patients were included in the final analysis. Right ventricular pacing burden (RVPB) ≥ 30% at 1 year was associated with a higher likelihood of heart failure (HF) readmission [adjusted hazard ratio (aHR): 6.333; 95% confidence interval [CI]: 1.417-28.311; P = 0.016] and composite endpoint of overall death and/or HF (aHR: 2.453; 95% CI: 1.040-5.786; P = 0.040). The RVPB ≥30% at 1 year was associated with higher atrial fibrillation burden (24.1 ± 40.6% vs. 1.2 ± 5.3%; P = 0.013) and a decrease in left ventricular ejection fraction (-5.0 ± 9.8% vs. + 1.1 ± 7.9%; P = 0.005). The predicting factors of the RVPB ≥30% at 1 year were the presence of RVPB ≥40% at 1 month and the valve implantation depth measured from non-coronary cusp ≥4.0 mm (aHR: 57.808; 95% CI: 12.489-267.584; P < 0.001 and aHR: 6.817; 95% CI: 1.829-25.402; P = 0.004). CONCLUSIONS: The RVPB ≥30% at 1 year was associated with worse outcomes. Clinical benefit of minimal RV pacing algorithms and biventricular pacing needs to be investigated.

Cor-Knot Use in SAVR Facilitates Coplanar Angle Adjustment During TAVR.

The Cor-Knot surgical tying device (LSI Solutions) is an automated suture fastener with a titanium-crimpable sleeve that facilitates a fast and secure knot. The device is an alternative to hand tying, minimizing operation time, and its increasing use is anticipated for minimally invasive cardiac surgeries or in patients with small surgical anatomy. As its use expands, the likelihood of encountering this knotting device during structural interventions may increase. In this case, during the TAVR procedure, the coplanar angle estimated from preoperative computed tomography scan was easily adjusted referencing the line of Cor-Knot in her aortic annulus without administrating contrast despite poor radiodensity from the Trifecta valve. In the coplanar view, the TAVR valve depth was well appreciated in reference to the Cor-Knot line and the TAVR valve was deployed under controlled pacing without contrast use. We achieved mean aortic pressure gradient of 9 mm Hg without paravalvular leakage or conduction abnormalities. She was discharged to home the next day without renal injury.

Water channel aquaporin 4 is required for T cell receptor mediated lymphocyte activation.

Aquaporins are a family of ubiquitously expressed transmembrane water channels implicated in a broad range of physiological functions. We have previously reported that aquaporin 4 (AQP4) is expressed on T cells and that treatment with a small molecule AQP4 inhibitor significantly delays T cell mediated heart allograft rejection. Using either genetic deletion or small molecule inhibitor, we show that AQP4 supports T cell receptor mediated activation of both mouse and human T cells. Intact AQP4 is required for optimal T cell receptor (TCR)-related signaling events, including nuclear translocation of transcription factors and phosphorylation of proximal TCR signaling molecules. AQP4 deficiency or inhibition impairs actin cytoskeleton rearrangements following TCR crosslinking, causing inferior TCR polarization and a loss of TCR signaling. Our findings reveal a novel function of AQP4 in T lymphocytes and identify AQP4 as a potential therapeutic target for preventing TCR-mediated T cell activation.

Combination of the STING Agonist MIW815 (ADU-S100) and PD-1 Inhibitor Spartalizumab in Advanced/Metastatic Solid Tumors or Lymphomas: An Open-Label, Multicenter, Phase Ib Study.

PURPOSE: The stimulator of IFN genes (STING) is a transmembrane protein that plays a role in the immune response to tumors. Single-agent STING agonist MIW815 (ADU-S100) has demonstrated immune activation but limited antitumor activity. This phase Ib, multicenter, dose-escalation study assessed the safety and tolerability of MIW815 plus spartalizumab (PDR001), a humanized IgG4 antibody against PD-1, in 106 patients with advanced solid tumors or lymphomas. PATIENTS AND METHODS: Patients were treated with weekly intratumoral injections of MIW815 (50-3,200 µg) on a 3-weeks-on/1-week-off schedule or once every 4 weeks, plus a fixed dose of spartalizumab (400 mg) intravenously every 4 weeks. RESULTS: Common adverse events were pyrexia (n = 23; 22%), injection site pain (n = 21; 20%), and diarrhea (n = 12; 11%). Overall response rate was 10.4%. The MTD was not reached. Pharmacodynamic biomarker analysis demonstrated on-target activity. CONCLUSIONS: The combination of MIW815 and spartalizumab was well tolerated in patients with advanced/metastatic cancers, including in patients with anti-PD-1 refractory disease. Minimal antitumor responses were seen.

Endoscopic vs Open Vein Harvest in Drug-Eluting Stents or Bypass Surgery for Left Main Disease Trial.

BACKGROUND: We investigated outcomes of coronary artery bypass grafting (CABG) with endoscopic vein harvest (EVH) vs open vein harvest (OVH) within the Evaluation of XIENCE Versus CABG (EXCEL) trial. METHODS: All patients in EXCEL randomized to CABG were included in this study. For this analysis, the primary end points were ischemia-driven revascularization (IDR) and graft stenosis or occlusion at 5 years. Additional end points were as follows: a composite of death from any cause, stroke, or myocardial infarction; bleeding; blood product transfusion; major arrhythmia; and infection requiring antibiotics. Event rates were based on Kaplan-Meier estimates in time-to-first-event analyses. RESULTS: Of the 957 patients randomized to CABG, 686 (71.7%) received at least 1 venous graft with 257 (37.5%) patients in the EVH group and 429 (62.5%) patients in the OVH group. At 5 years, IDR was higher (11.5% vs 6.7%; P = .047) in the EVH group. At 5 years, rates of graft stenosis or occlusion (9.7% vs 5.4%; P = .054) and the primary end point (17.4% vs 20.9%; P = .27) were similar. In-hospital bleeding (11.3% vs 13.8%; P = .35), in-hospital blood product transfusion (12.8% vs 13.1%; P = .94), and infection requiring antibiotics within 1 month (13.6% vs 16.8%; P = .27) were similar between EVH and OVH patients. Major arrhythmia in the hospital (19.8% vs 13.5%; P = .03) and within 1 month (21.8% vs 15.4%; P = .03) was higher in EVH patients. CONCLUSIONS: IDR at 5 years was higher in the EVH group. EVH and OVH patients had similar rates of graft stenosis or occlusion and the composite of death, stroke, or myocardial infarction at 5 years.

Postdischarge Pain and Opioid Use After Cardiac Surgery: A Prospective Cohort Study.

BACKGROUND: The rate of chronic opioid use after cardiac surgery is high compared with other surgical specialties; however evidence regarding optimal prescribing is limited. The purpose of this study was to evaluate patterns of opioid consumption after cardiac surgery to guide prescribing practices. METHODS: Consecutive patients undergoing sternotomy-based cardiac operations were considered for enrollment. Patients with opioid use within 3 months of surgery and those discharged to a nonhome facility were excluded. A patient diary and researcher-directed pill count was used to track pain and opioid use for 10 days after discharge. RESULTS: One hundred four patients were included in the final analysis. Of the 63 patients discharged with an opioid, 22 (34.9%) used none and 12 (19.0%) used fewer than half of the pills prescribed. Overall, pain and opioid consumption decreased significantly throughout the discharge period (P < .001). In those who used opioids after discharge, median total consumption was 64 morphine milligram equivalents (interquartile range, 38-128), or the equivalent of 9 oxycodone 5-mg tablets. Patients who used opioids were younger (60.9 vs 70.0, P < .001), but there were no differences based on sex, history of substance use, smoking, or procedure. After risk adjustment the mean pain score ≥ 3 on the day of discharge was predictive of opioid use (odds ratio, 2.9; 95% confidence interval, 1.8-4.8; P < .001). Most patients (88.5%) were satisfied or very satisfied with pain management. CONCLUSIONS: Fewer than half of all patients used opioids after discharge in this study. These data support the need for the development of prescription recommendations after cardiac surgery.

Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor.

Objectives: Sabatolimab is a humanized monoclonal antibody (hIgG4, S228P) directed against human T-cell immunoglobulin domain and mucin domain-3 (TIM-3). Herein, we describe the development and characterization of sabatolimab. Methods: Sabatolimab was tested for binding to its target TIM-3 and blocking properties. The functional effects of sabatolimab were tested in T-cell killing and myeloid cell cytokine assays. Antibody-mediated cell phagocytosis (ADCP) by sabatolimab was also assessed. Results: Sabatolimab was shown to (i) enhance T-cell killing and inflammatory cytokine production by dendritic cells (DCs); (ii) facilitate the phagocytic uptake of TIM-3-expressing target cells; and (iii) block the interaction between TIM-3 and its ligands PtdSer/galectin-9. Conclusion: Taken together, our results support both direct anti-leukemic effects and immune-mediated modulation by sabatolimab, reinforcing the notion that sabatolimab represents a novel immunotherapy with immuno-myeloid activity, holding promise for the treatment of myeloid cell neoplasms.

Preclinical Characterization and Phase I Study of an Anti-HER2-TLR7 Immune-Stimulator Antibody Conjugate in Patients with HER2+ Malignancies.

Immune-stimulator antibody conjugates (ISAC) combining tumor-targeting monoclonal antibodies with immunostimulatory agents allow targeted delivery of immune activators into tumors. NJH395 is a novel, first-in-class ISAC comprising a Toll-like receptor 7 (TLR7) agonist conjugated to an anti-HER2 antibody via a noncleavable linker payload. Preclinical characterization showed ISAC-mediated activation of myeloid cells in the presence of antigen-expressing cancer cells, with antigen targeting and TLR7 agonism contributing to antitumor activity. Safety, efficacy, immunogenicity, pharmacokinetics, and pharmacodynamics were investigated in a phase I, multicenter, open-label study in patients with HER2+ non-breast advanced malignancies (NCT03696771). Data from 18 patients enrolled in single ascending dose escalation demonstrated delivery of the TLR7-agonist payload in HER2+ tumor cells and induction of type I IFN responses, which correlated with immune modulation in the tumor microenvironment. Cytokine release syndrome was a common, but manageable, drug-related adverse event. Antidrug antibodies and neuroinflammation at high doses represented significant clinical challenges. Data provide proof-of-mechanism and critical insights for novel immunotherapies.

Risk stratification of new persistent left bundle branch block after transcatheter aortic valve implantation

ABSTRACT Previous studies reported that new-onset persistent left bundle branch block (NOP-LBBB) was related to worse outcomes after transcatheter aortic valve implantation (TAVI). However, these results can be confounded by the presence of permanent pacemaker (PPM) implantation before and after TAVI. Long-term outcomes and the risk stratification of NOP-LBBB not having PPM implantation before and after TAVI have not been fully investigated. This is an international, multicenter, retrospective study of patients who underwent TAVI from July 31, 2007, to May 8, 2020. A total of 2,240 patients were included, and 17.5% of patients developed NOP-LBBB. NOP-LBBB was associated with cardiac mortality (adjusted hazard ratio [aHR] 1.419, 95% confidence interval [CI] 1.014 to 1.985, p = 0.041) and the composite outcomes of cardiac mortality and/or heart failure readmission (aHR 1.313, 95% CI 1.027 to 1.678, p = 0.030). Patients who developed NOP-LBBB with pre-TAVI left ventricular ejection fraction (LVEF) <40% were significantly associated with cardiac mortality (aHR 2.049, 95% CI 1.039 to 4.041, p = 0.038), heart failure (aHR 3.990, 95% CI 2.362 to 6.741, p <0.001), and the composite outcome (aHR 2.729, 95% CI 1.703 to 4.374, p <0.001). Although NOP-LBBB with pre-TAVI LVEF >40% had a significant decrease in LVEF 6 to 12 months after TAVI (-1.8 ± 9.7% vs +0.6 ± 8.1%, p = 0.003), NOP-LBBB with pre-TAVI LVEF <40% had a significant increase in LVEF 6 to 12 months after TAVI (+9.7 ± 13.6% vs +13.0 ± 11.7%, p = 0.157). In conclusion, patients with NOP-LBBB without pre-TAVI and post-TAVI PPM developed significantly worse long-term outcomes, especially in patients with pre-TAVI LVEF <40%. Further prospective investigation should be undertaken.

Percutaneous mechanical thrombectomy and extracorporeal membranous oxygenation: A case series.

BACKGROUND: Massive or high-risk pulmonary embolism (PE) is a potentially life-threatening diagnosis with significant morbidity and mortality if treatment is delayed. Extracorporeal membrane oxygenation (ECMO) and large bore thrombectomy (LBT) in isolation have been used to stabilize and treat patients with massive PE, however, literature describing the combination of both modalities is lacking. We present a case series involving 9 patients who underwent combined ECMO and LBT and their outcomes. METHODS: This was a retrospective chart review of patients with confirmed PE, who underwent LBT and ECMO. We retrospectively captured clinical, therapeutic, and outcome data at the time of pulmonary embolism response team (PERT) activation and during the follow-up period for up to 90 days. RESULTS: Nine patients who had PERT activation with confirmed PE diagnosis have undergone combined LBT and ECMO initiation since the advent of our PERT program. The median age was 57 (range 28-68) years. Six patients out of 9 (55%) had cardiac arrest before therapy. All patients exhibited right heart strain on computed tomography and echocardiogram. The median ECMO duration was 5 days (range 2.3-11.6 days), with mean hospitalization of 16.1 days (range 1.5-30.9). Mortality was 22% at 90-day follow-up period. CONCLUSION: Patients with massive pulmonary embolism who suffer cardiac arrest have significant morbidity and mortality. ECMO in combination with LBT is a viable treatment option for patients with significant hemodynamic compromise.