V stenting technique with covered stents for the management of ostial circumflex perforation: Good or bad idea?

We report the case of a redo Ross surgery complicated by an ostial left circumflex occlusion requiring emergent percutaneous coronary intervention. The latter was complicated by coronary perforation treated by two covered stents with V-stenting technique. After immediate success, the clinical course was marked by acute stent thrombosis requiring emergent coronary bypass. Learning objectives: Ostial left circumflex perforation is a rare and potentially fatal complication that is challenging to manage. V stenting technique with two covered stents could be used as a life-saving procedure, but is associated with a high thrombotic risk.

Negative Impact of TET2 Mutations on Long-Term Survival After Transcatheter Aortic Valve Replacement.

Clonal hematopoiesis of indeterminate potential (CHIP) is considered as being a novel age-related risk factor for cardiovascular diseases. By capture-sequencing of a 67-gene panel, we established a large spectrum of CHIP in 258 patients with aortic valve stenosis undergoing transcatheter aortic valve replacement (TAVR) and assessed their association with long-term survival after TAVR. One or several CHIP variants in 35 genes were identified in 68% of the cohort, DNMT3A and TET2 being the 2 most frequently mutated genes. Patients carrying a TET2-CHIP-driver variant with low variant allele frequency (2%-10%) had a significant decrease in overall survival 5 years after TAVR.

Shear Forces Induced Platelet Clearance Is a New Mechanism of Thrombocytopenia.

BACKGROUND: Thrombocytopenia has been consistently described in patients with extracorporeal membrane oxygenation (ECMO) and associated with poor outcome. However, the prevalence and underlying mechanisms remain largely unknown, and a device-related role of ECMO in thrombocytopenia has been hypothesized. This study aims to investigate the mechanisms underlying thrombocytopenia in ECMO patients. METHODS: In a prospective cohort of 107 ECMO patients, we investigated platelet count, functions, and glycoprotein shedding. In an ex vivo mock circulatory ECMO loop, we assessed platelet responses and VWF (von Willebrand factor)-GP Ibα (glycoprotein Ibα) interactions at low- and high-flow rates, in the presence or absence of red blood cells. The clearance of human platelets subjected or not to ex vivo perfusion was studied using an in vivo transfusion model in NOD/SCID (nonobese diabetic/severe combined Immunodeficient) mice. RESULTS: In ECMO patients, we observed a time-dependent decrease in platelet count starting 1 hour after device onset, with a mean drop of 7%, 35%, and 41% at 1, 24, and 48 hours post-ECMO initiation (P=0.00013, P<0.0001, and P<0.0001, respectively), regardless of the type of ECMO. This drop in platelet count was associated with a decrease in platelet GP Ibα expression (before: 47.8±9.1 versus 24 hours post-ECMO: 42.3±8.9 mean fluorescence intensity; P=0.002) and an increase in soluble GP Ibα plasma levels (before: 5.6±3.3 versus 24 hours post-ECMO: 10.8±4.1 µg/mL; P<0.0001). GP Ibα shedding was also observed ex vivo and was unaffected by (1) red blood cells, (2) the coagulation potential, (3) an antibody blocking VWF-GP Ibα interaction, (4) an antibody limiting VWF degradation, and (5) supraphysiological VWF plasma concentrations. In contrast, GP Ibα shedding was dependent on rheological conditions, with a 2.8-fold increase at high- versus low-flow rates. Platelets perfused at high-flow rates before being transfused to immunodeficient mice were eliminated faster in vivo with an accelerated clearance of GP Ibα-negative versus GP Ibα-positive platelets. CONCLUSIONS: ECMO-associated shear forces induce GP Ibα shedding and thrombocytopenia due to faster clearance of GP Ibα-negative platelets. Inhibiting GP Ibα shedding could represent an approach to reduce thrombocytopenia during ECMO.

Transcatheter interventions for left-sided valvular heart disease complicated by cardiogenic shock: a consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) in collaboration with the Association for Acute Cardiovascular Care (ACVC) and the ESC Working Group on Cardiovascular Surgery.

Valvular heart disease (VHD) is one of the most frequent causes of heart failure (HF) and is associated with poor prognosis, particularly among patients with conservative management. The development and improvement of catheter-based VHD interventions have broadened the indications for transcatheter valve interventions from inoperable/high-risk patients to younger/lower-risk patients. Cardiogenic shock (CS) associated with severe VHD is a clinical condition with a very high risk of mortality for which surgical treatment is often deemed a prohibitive risk. Transcatheter valve interventions might be a promising alternative in this setting given that they are less invasive. However, supportive scientific evidence is scarce and often limited to small case series. Current guidelines on VHD do not contain specific recommendations on how to manage patients with both VHD and CS. The purpose of this clinical consensus statement, developed by a group of international experts invited by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) Scientific Documents and Initiatives Committee, is to perform a review of the available scientific evidence on the management of CS associated with left-sided VHD and to provide a rationale and practical approach for the application of transcatheter valve interventions in this specific clinical setting.

Minimum Core Data Elements for Transcatheter Mitral Therapies: Scientific Statement by PASSION CV, HVC, and TVTR.

Mitral regurgitation is the most common valvular disease and is estimated to affect over 5 million Americans. Real-world data collection contributes to safety and effectiveness evidence for the U.S. Food and Drug Administration, quality evaluation for the Centers for Medicare and Medicaid Services and hospitals, and clinical best practice research. We aimed to establish a minimum core data set in mitral interventions to promote efficient, reusable real-world data collection for all of these purposes. Two expert task forces separately evaluated and reconciled a list of candidate elements derived from: 1) 2 ongoing transcatheter mitral trials; and 2) a systemic literature review of high-impact mitral trials and U.S multicenter, multidevice registries. From 703 unique data elements considered, unanimous consensus agreement was achieved on 127 "core" data elements, with the most common reasons for exclusion from the minimum core data set being burden or difficulty in accurate assessment (41.2%), duplicative information (25.0%), and low likelihood of affecting outcomes (19.6%). After a systematic review and extensive discussions, a multilateral group of academicians, industry representatives, and regulators established and implemented into the national Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapies Registry 127 interoperable, reusable core data elements to support more efficient, consistent, and informative transcatheter mitral device evidence for regulatory submissions, safety surveillance, best practice development, and hospital quality assessments.

Cerebrovascular Events After Transcatheter Edge-to-Edge Repair and Guideline-Directed Medical Therapy in the COAPT Trial.

BACKGROUND: Little is known regarding the risk of cerebrovascular events (CVE) in patients with heart failure and severe secondary mitral regurgitation treated with transcatheter edge-to-edge repair (TEER). OBJECTIVES: The study sought to examine the incidence, predictors, timing, and prognostic impact of CVE (stroke or transient ischemic attack) in the COAPT (Cardiovascular Outcomes Assessment of the Mitraclip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial. METHODS: A total of 614 patients with heart failure and severe secondary mitral regurgitation were randomized to TEER plus guideline-directed medical therapy (GDMT) vs GDMT alone. RESULTS: At 4-year follow-up, 50 CVEs occurred in 48 (7.8%) of the 614 total patients enrolled in the COAPT trial; Kaplan-Meier event rates were 12.3% in the TEER group and 10.2 in the GDMT alone group (P = 0.91). Within 30 days of randomization, CVE occurred in 2 (0.7%) patients randomized to TEER and 0% randomized to GDMT (P = 0.15). Baseline renal dysfunction and diabetes were independently associated with increased risk of CVE, while baseline anticoagulation was associated with a reduction of CVE. A significant interaction was present between treatment group and anticoagulation such that TEER compared with GDMT alone was associated with a reduced risk of CVE among patients with anticoagulation (adjusted HR: 0.24; 95% CI: 0.08-0.73) compared with an increased risk of CVE in patients without anticoagulation (adjusted HR: 2.27; 95% CI: 1.08-4.81; Pinteraction = 0.001). CVE was an independent predictor of death within 30 days after the event (HR: 14.37; 95% CI: 7.61, 27.14; P < 0.0001). CONCLUSIONS: In the COAPT trial, the 4-year rate of CVE was similar after TEER or GDMT alone. CVE was strongly associated with mortality. Whether anticoagulation is effective at reducing CVE risk after TEER warrants further study. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT); NCT01626079).

Management of coronary artery disease in patients undergoing transcatheter aortic valve implantation. A clinical consensus statement from the European Association of Percutaneous Cardiovascular Interventions in collaboration with the ESC Working Group on Cardiovascular Surgery.

Significant coronary artery disease (CAD) is a frequent finding in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI), and the management of these two conditions becomes of particular importance with the extension of the procedure to younger and lower-risk patients. Yet, the preprocedural diagnostic evaluation and the indications for treatment of significant CAD in TAVI candidates remain a matter of debate. In this clinical consensus statement, a group of experts from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) in collaboration with the European Society of Cardiology (ESC) Working Group on Cardiovascular Surgery aims to review the available evidence on the topic and proposes a rationale for the diagnostic evaluation and indications for percutaneous revascularisation of CAD in patients with severe aortic stenosis undergoing transcatheter treatment. Moreover, it also focuses on commissural alignment of transcatheter heart valves and coronary re-access after TAVI and redo-TAVI.

Transcatheter aortic valve implantation using the SAPIEN 3 valve to treat aortic regurgitation: The French multicentre S3AR study.

BACKGROUND: Transcatheter aortic valve implantation now has a major role in the treatment of patients with severe aortic stenosis. However, evidence is scarce on its feasibility and safety to treat patients with pure aortic regurgitation. AIMS: We sought to evaluate the results of transcatheter aortic valve implantation using the balloon-expandable SAPIEN 3 transcatheter heart valve (Edwards Lifesciences, Irvine, CA, USA) in patients with pure aortic regurgitation on native non-calcified valves. METHODS: We conducted a retrospective and prospective French multicentre observational study. We included all patients with symptomatic severe pure aortic regurgitation on native non-calcified valves, contraindicated to or at high risk for surgical valve replacement, who underwent transcatheter aortic valve implantation using the SAPIEN 3 transcatheter heart valve. RESULTS: A total of 37 patients (male sex, 73%) with a median age of 81years (interquartile range 69-85years) were screened using transthoracic echocardiography and computed tomography and were included at eight French centres. At baseline, 83.8% of patients (n=31) had dyspnoea New York Heart Association class≥III. The device success rate was 94.6% (n=35). At 30days, the all-cause mortality rate was 8.1% (n=3) and valve migration occurred in 10.8% of cases (n=4). Dyspnoea New York Heart Association class≤II was seen in 86.5% of patients (n=32), and all survivors had aortic regurgitation grade≤1. At 1-year follow-up, all-cause mortality was 16.2% (n=6), 89.7% (n=26/29) of survivors were in New York Heart Association class≤II and all had aortic regurgitation grade≤2. CONCLUSION: Transcatheter aortic valve implantation using the SAPIEN 3 transcatheter heart valve seems promising to treat selected high-risk patients with pure aortic regurgitation on non-calcified native valves, contraindicated to surgical aortic valve replacement.

BAlloon expandable vs. SElf expanding transcatheter vaLve for degenerated bioprosthesIs: design and rationale of the BASELINE trial.

BACKGROUND: Surgical aortic valve bioprostheses may degenerate over time and require redo intervention. Transcatheter aortic valve replacement (TAVR) is a less invasive alternative to redo surgery. The BAlloon Expandable vs. SElf Expanding Transcatheter VaLve for Degenerated BioprosthesIs (BASELINE) trial was designed to compare the performance of the balloon-expandable SAPIEN-3 Ultra and the self-expanding EVOLUT PRO+ valve systems in symptomatic patients with a failing surgical bioprosthesis. METHODS: The BASELINE trial is an investigator-initiated, non-funded, prospective, randomized, open-label, superiority trial enrolling a total of 440 patients in up to 50 sites in 12 countries in Europe and North-America. The primary endpoint is device success at 30-days defined by the Valve Academic Research Consortium-3 Criteria as the composite of technical success, freedom from mortality, freedom for surgery or intervention related to the device or to a major vascular or access-related or cardiac structural complication with an intended performance of the valve (mean gradient <20 mmHg and less than moderate aortic regurgitation). The co-primary endpoint at 1 year is defined as the composite of all-cause death, disabling stroke, rehospitalization for heart failure or valve related problems. Independent Core Laboratories will conduct uniform analyses of echocardiography (pre-, post-, 1-year post-procedure), multi-sliced computed tomography (pre-, and if available post-procedure) and cine-fluoroscopy studies. CONCLUSIONS: The BASELINE trial is a head-to-head comparative trial investigating the 2 most used contemporary transcatheter heart valves for the treatment of a failing surgical aortic bioprosthesis. (ClinicalTrials.gov number NCT04843072).

A nanobody against the VWF A3 domain detects ADAMTS13-induced proteolysis in congenital and acquired VWD.

von Willebrand factor (VWF) is a multimeric protein, the size of which is regulated via ADAMTS13-mediated proteolysis within the A2 domain. We aimed to isolate nanobodies distinguishing between proteolyzed and non-proteolyzed VWF, leading to the identification of a nanobody (designated KB-VWF-D3.1) targeting the A3 domain, the epitope of which overlaps the collagen-binding site. Although KB-VWF-D3.1 binds with similar efficiency to dimeric and multimeric derivatives of VWF, binding to VWF was lost upon proteolysis by ADAMTS13, suggesting that proteolysis in the A2 domain modulates exposure of its epitope in the A3 domain. We therefore used KB-VWF-D3.1 to monitor VWF degradation in plasma samples. Spiking experiments showed that a loss of 10% intact VWF could be detected using this nanobody. By comparing plasma from volunteers to that from congenital von Willebrand disease (VWD) patients, intact-VWF levels were significantly reduced for all VWD types, and most severely in VWD type 2A-group 2, in which mutations promote ADAMTS13-mediated proteolysis. Unexpectedly, we also observed increased proteolysis in some patients with VWD type 1 and VWD type 2M. A significant correlation (r = 0.51, P < .0001) between the relative amount of high-molecular weight multimers and levels of intact VWF was observed. Reduced levels of intact VWF were further found in plasmas from patients with severe aortic stenosis and patients receiving mechanical circulatory support. KB-VWF-D3.1 is thus a nanobody that detects changes in the exposure of its epitope within the collagen-binding site of the A3 domain. In view of its unique characteristics, it has the potential to be used as a diagnostic tool to investigate whether a loss of larger multimers is due to ADAMTS13-mediated proteolysis.

Modulation of inflammatory M1-macrophages phenotype by valvular interstitial cells.

BACKGROUND: Aortic valve stenosis involves inflammation, excess deposition of a collagen-rich extracellular matrix, and calcification. Recent studies have shown that M1 or inflammatory macrophages derived from infiltrating monocytes promote calcification of valvular interstitial cells, the most prevalent cell type of the aortic valve. We hypothesized that valvular interstitial cells could modulate inflammatory macrophages phenotype. METHODS: We first assessed macrophage phenotype in human aortic valve stenosis and control aortic valves from donors. Then, we examined profibrotic and inflammatory-related gene expression in valves and valvular interstitial cells. Finally, we investigated whether valvular interstitial cells can modify the phenotype of inflammatory macrophages. RESULTS: Circulating monocytes and plasma transforming growth factor beta-1 levels of patients with aortic valve stenosis were significantly higher compared with patients without aortic valve stenosis. Histologic analysis of thickened spongiosa of the aortic valve from patients with aortic valve stenosis showed a high macrophage infiltration but a low matrix metalloproteinase-9 expression compared with control aortic valves. On the other hand, valvular interstitial cell culture of aortic valve stenosis exhibited a profibrotic phenotype with a high expression of transforming growth factor beta-1 and transforming growth factor beta-1/transforming growth factor beta-3 ratio but a decreased expression of the peroxisome proliferator-activated receptor gamma nuclear receptor. Valvular interstitial cell-conditioned media of aortic valve stenosis led to a decrease in enzymatic activity of matrix metalloproteinase-9 and an increase in production of collagen in inflammatory macrophages compared with valvular interstitial cell-conditioned media from control aortic valve donors. CONCLUSIONS: These findings indicate that profibrotic valvular interstitial cells promote the imbalance of extracellular matrix remodeling by reducing matrix metalloproteinase-9 production on inflammatory macrophages that lead to excessive collagen deposition observed in aortic valve stenosis. Further investigation is needed to clarify the role of transforming growth factor beta-1/proliferator-activated receptor gamma nuclear receptor/matrix metalloproteinase-9 in aortic valve stenosis.

Impact of Smoking Status on Mortality in STEMI Patients Undergoing Mechanical Reperfusion for STEMI: Insights from the ISACS-STEMI COVID-19 Registry.

The so-called "smoking paradox", conditioning lower mortality in smokers among STEMI patients, has seldom been addressed in the settings of modern primary PCI protocols. The ISACS−STEMI COVID-19 is a large-scale retrospective multicenter registry addressing in-hospital mortality, reperfusion, and 30-day mortality among primary PCI patients in the era of the COVID-19 pandemic. Among the 16,083 STEMI patients, 6819 (42.3%) patients were active smokers, 2099 (13.1%) previous smokers, and 7165 (44.6%) non-smokers. Despite the impaired preprocedural recanalization (p < 0.001), active smokers had a significantly better postprocedural TIMI flow compared with non-smokers (p < 0.001); this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. Active smokers had a significantly lower in-hospital (p < 0.001) and 30-day (p < 0.001) mortality compared with non-smokers and previous smokers; this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. In conclusion, in our population, active smoking was significantly associated with improved epicardial recanalization and lower in-hospital and 30-day mortality compared with previous and non-smoking history.

[TAVR : Imaging for an optimal femoral approach]. / TAVI : imagerie pour une gestion parfaite de la voie d'abord fémorale.

Both computed tomography (CT) angiography and vascular ultrasound have a major role before and during a transfemoral approach to TAVR. CT angiography will determine whether the patient is eligible for a femoral approach. Peri-procedural arterial ultrasound will be helpful to improve safety and optimize results during the femoral approach. Being able to interpret both of these imaging modalities is of paramount importance for any interventional cardiologist who practices structural interventions.

Apixaban and Valve Thrombosis After Transcatheter Aortic Valve Replacement: The ATLANTIS-4D-CT Randomized Clinical Trial Substudy.

BACKGROUND: Subclinical obstructive valve thrombosis after transcatheter aortic valve replacement (TAVR) is of uncertain frequency and clinical impact. OBJECTIVES: The aim of this study was to determine the effects of apixaban vs standard of care on post-TAVR valve thrombosis detected by 4-dimensional (4D) computed tomography. METHODS: The randomized ATLANTIS (Anti-Thrombotic Strategy to Lower All Cardiovascular and Neurologic Ischemic and Hemorrhagic Events After Trans-Aortic Valve Implantation for Aortic Stenosis) trial demonstrated that apixaban 5 mg twice daily was not superior to standard of care (vitamin K antagonists or antiplatelet therapy) after successful TAVR and was associated with similar safety but with more noncardiovascular deaths. Three months after randomization, 4D computed tomography was proposed to all patients to determine the percentage of patients with ≥1 prosthetic valve leaflet with grade 3 or 4 reduced leaflet motion or grade 3 or 4 hypoattenuated leaflet thickening (the primary endpoint) in the intention-to-treat population. RESULTS: Seven hundred sixty-two participants had complete multiphase datasets and were included in the 4D computed tomographic analysis. The primary endpoint occurred in 33 (8.9%) and 51 (13.0%) patients in the apixaban and standard-of-care groups, respectively. It was reduced with apixaban vs antiplatelet therapy (OR: 0.51; 95% CI: 0.30-0.86) but not vs vitamin K antagonists (OR: 1.80; 95% CI: 0.62-5.25) (Pinteraction = 0.037). The composite of death, myocardial infarction, any stroke, or systemic embolism at 1 year occurred in 10.7% (n = 9 of 84) and 7.1% (n = 48 of 178) of patients with and without subclinical valve thrombosis at 90 days, respectively (HR: 1.68; 95% CI: 0.82-3.44). CONCLUSIONS: Apixaban reduced subclinical obstructive valve thrombosis in the majority of patients who underwent TAVR without having an established indication for anticoagulation. This study was not powered for clinical outcomes. (Anti-Thrombotic Strategy After Trans-Aortic Valve Implantation for Aortic Stenosis [ATLANTIS]; NCT02664649).

Bioprosthetic Aortic Valve Hemodynamics: Definitions, Outcomes, and Evidence Gaps: JACC State-of-the-Art Review.

A virtual workshop was organized by the Heart Valve Collaboratory to identify areas of expert consensus, areas of disagreement, and evidence gaps related to bioprosthetic aortic valve hemodynamics. Impaired functional performance of bioprosthetic aortic valve replacement is associated with adverse patient outcomes; however, this assessment is complicated by the lack of standardization for labelling, definitions, and measurement techniques, both after surgical and transcatheter valve replacement. Echocardiography remains the standard assessment methodology because of its ease of performance, widespread availability, ability to do serial measurements over time, and correlation with outcomes. Management of a high gradient after replacement requires integration of the patient's clinical status, physical examination, and multimodality imaging in addition to shared patient decisions regarding treatment options. Future priorities that are underway include efforts to standardize prosthesis sizing and labelling for both surgical and transcatheter valves as well as trials to characterize the consequences of adverse hemodynamics.

Cerebral Microbleeds During Transcatheter Aortic Valve Replacement: A Prospective Magnetic Resonance Imaging Cohort.

BACKGROUND: Cerebral microbleeds (CMBs) have been observed in healthy elderly people undergoing systematic brain magnetic resonance imaging. The potential role of acute triggers on the appearance of CMBs remains unknown. We aimed to describe the incidence of new CMBs after transcatheter aortic valve replacement (TAVR) and to identify clinical and procedural factors associated with new CMBs including hemostatic measures and anticoagulation management. METHODS: We evaluated a prospective cohort of patients with symptomatic aortic stenosis referred for TAVR for CMBs (METHYSTROKE [Identification of Epigenetic Risk Factors for Ischemic Complication During the TAVR Procedure in the Elderly]). Standardized neurologic assessment, brain magnetic resonance imaging, and analysis of hemostatic measures including von Willebrand factor were performed before and after TAVR. Numbers and location of microbleeds on preprocedural magnetic resonance imaging and of new microbleeds on postprocedural magnetic resonance imaging were reported by 2 independent neuroradiologists blinded to clinical data. Measures associated with new microbleeds and postprocedural outcome including neurologic functional outcome at 6 months were also examined. RESULTS: A total of 84 patients (47% men, 80.9±5.7 years of age) were included. On preprocedural magnetic resonance imaging, 22 patients (26% [95% CI, 17%-37%]) had at least 1 microbleed. After TAVR, new microbleeds were observed in 19 (23% [95% CI, 14%-33%]) patients. The occurrence of new microbleeds was independent of the presence of microbleeds at baseline and of diffusion-weighted imaging hypersignals. In univariable analysis, a previous history of bleeding (P=0.01), a higher total dose of heparin (P=0.02), a prolonged procedure (P=0.03), absence of protamine reversion (P=0.04), higher final activated partial thromboplastin time (P=0.05), lower final von Willebrand factor high-molecular-weight:multimer ratio (P=0.007), and lower final closure time with adenosine-diphosphate (P=0.02) were associated with the occurrence of new postprocedural microbleeds. In multivariable analysis, a prolonged procedure (odds ratio, 1.22 [95% CI, 1.03-1.73] for every 5 minutes of fluoroscopy time; P=0.02) and postprocedural acquired von Willebrand factor defect (odds ratio, 1.42 [95% CI, 1.08-1.89] for every lower 0.1 unit of high-molecular-weight:multimer ratio; P=0.004) were independently associated with the occurrence of new postprocedural microbleeds. New CMBs were not associated with changes in neurologic functional outcome or quality of life at 6 months. CONCLUSIONS: One out of 4 patients undergoing TAVR has CMBs before the procedure and 1 out of 4 patients develops new CMBs. Procedural or antithrombotic management and persistence of acquired von Willebrand factor defect were associated with the occurrence of new CMBs. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02972008.

Thrombus formation during ECMO: Insights from a detailed histological analysis of thrombus composition.

OBJECTIVES: Intra-device thrombosis remains one of the most common complications during extracorporeal membrane oxygenation (ECMO). Despite anticoagulation, approximately 35% of patients develop thrombi in the membrane oxygenator, pump heads, or tubing. The aim of this study was to describe the molecular and cellular features of ECMO thrombi and to study the main drivers of thrombus formation at different sites in the ECMO circuits. APPROACH AND RESULTS: Thrombi (n = 85) were collected immediately after veno-arterial-(VA)-ECMO circuit removal from 25 patients: 23 thrombi from the pump, 25 from the oxygenator, and 37 from the tubing. Quantitative histological analysis was performed for the amount of red blood cells (RBCs), platelets, fibrin, von Willebrand factor (VWF), leukocytes, and citrullinated histone H3 (H3Cit). ECMO thrombi consist of a heterogenous composition with fibrin and VWF being the major thrombus components. A clustering analysis of the four major histological parameters identified two typical thrombus types: RBC-rich and RBC-poor/fibrin-rich thrombi with no significant differences in VWF and platelet content. Thrombus composition was not associated with the thrombus location, except for higher amounts of H3Cit that were found in pump and oxygenator thrombi compared to tubing samples. We observed higher blood leukocyte count and lactate dehydrogenase levels in patients with fibrin-rich thrombi. CONCLUSION: We found that thrombus composition is heterogenous, independent of their location, consisting of two types: RBC-rich and a fibrin-rich types. We also found that NETs play a minor role. These findings are important to improve current anticoagulation strategies in ECMO.