Definitions of major bleeding for predicting mortality in critically ill adult patients who survived 24 hours while supported with peripheral veno-arterial extracorporeal membrane oxygenation for cardiogenic shock: a comparative historical cohort study.

PURPOSE: The severity of bleeding events is heterogeneously defined during peripheral veno-arterial extracorporeal membrane oxygenation (pVA-ECMO). We studied three bleeding definitions in pVA-ECMO: the Extracorporeal Life Support Organization (ELSO)-serious bleeding, the Bleeding Academic Research Consortium (BARC), and the universal definition of postoperative bleeding (UPDB) classifications. METHODS: We included consecutive adult patients supported by pVA-ECMO for refractory cardiogenic shock admitted to Lille academic hospitals between January 2013 and December 2019. We assessed the association of bleeding definitions with the primary endpoint of 28-day all-cause mortality with the use of multivariate models accounting for time-dependent and competing variables. We compared models' performances using the Harrell's C-Index and the Akaike information criteria. RESULTS: Twenty-eight-day mortality occurred in 128/308 (42%) 308 patients. The ELSO-serious bleeding (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.09 to 2.56) and BARC ≥ type 2 (HR, 1.55; 95% CI, 1.01 to 2.37) were associated with 28-day mortality (Harrell's C-index, 0.69; 95% CI, 0.63 to 0.74 for both). Predictors of ELSO-serious bleeding were postcardiotomy, body mass index, baseline platelets count, fibrinogen, and hemoglobin levels. CONCLUSION: Extracorporeal Life Support Organization-serious bleeding and BARC ≥ type 2 are relevant definitions of major bleeding regarding their association with mortality in critically ill patients who survived the first 24 hr while supported with pVA-ECMO for cardiogenic shock. STUDY REGISTRATION: CERAR (IRB 00010254-2022-050, Paris, France); first submitted on 18 April 2022.

RéSUMé: OBJECTIF: La gravité des événements hémorragiques est définie de manière hétérogène pendant une oxygénation par membrane extracorporelle veino-artérielle périphérique (ECMO-VA périphérique). Nous avons étudié trois définitions du saignement sous ECMO-VA périphérique : les classifications des saignements graves selon l'Extracorporeal Life Support Organization (ELSO), celles du Bleeding Academic Research Consortium (BARC) et la définition universelle du saignement postopératoire (UPDB). MéTHODE: Nous avons inclus des patient·es adultes pris·es en charge de manière consécutive par ECMO-VA périphérique à la suite d'un choc cardiogénique réfractaire et admis·es dans les centres hospitaliers universitaires de Lille entre janvier 2013 et décembre 2019. Nous avons évalué l'association des définitions du saignement avec le critère d'évaluation principal de mortalité toutes causes confondues à 28 jours à l'aide de modèles multivariés tenant compte des variables dépendantes du temps et concurrentes. Nous avons comparé les performances des modèles à l'aide de l'indice C de Harrell et du critère d'information d'Akaike. RéSULTATS: La mortalité à 28 jours est survenue chez 128/308 (42 %) patient·es. Le saignement grave selon l'ELSO (rapport de risque [RR], 1,67; intervalle de confiance [IC] à 95 %, 1,09 à 2,56) et une classification BARC ≥ type 2 (RR, 1,55; IC 95 %, 1,01 à 2,37) étaient associés à une mortalité à 28 jours (indice C de Harrell, 0,69; IC 95 %, 0,63 à 0,74 pour les deux). Les prédicteurs d'hémorragie grave selon l'ELSO étaient la postcardiotomie, l'indice de masse corporelle, la numération plaquettaire initiale, le taux de fibrinogène et les taux d'hémoglobine. CONCLUSION: Les définitions du saignement grave de l'Extracorporeal Life Support Organization et une classification BARC ≥ type 2 sont des définitions pertinentes des saignements majeurs en ce qui touche à leur association avec la mortalité chez les personnes gravement malades qui ont survécu aux premières 24 heures alors qu'elles étaient prises en charge par ECMO-VA périphérique à la suite d'un choc cardiogénique. ENREGISTREMENT DE L'éTUDE: CERAR (IRB 00010254-2022-050, Paris, France); soumis pour la première fois le 18 avril 2022.

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.

David Procedure: A 21-year Experience With 300 Patients.

BACKGROUND: Valve-sparing aortic root replacement with the David procedure is an alternative to the Bentall procedure in patients with aortic root aneurysm. The aim of this study was to describe our long-term experience with this technique and the predictive factors of late failure. METHODS: Between January 1998 and August 2019, 300 consecutive patients underwent a David procedure. Clinical and echocardiographic early- and long-term outcomes were analyzed. Median follow-up was 7.0 years (range, 4.1-11.5), with 98.3% complete. RESULTS: Early mortality was 1%. No early valve-related reoperations occurred. There were 9 cardiac-related deaths and 22 reinterventions (19 valve-related). All patients survived reoperation. In 3 patients reintervention consisted of transcatheter aortic valve implantation. Overall survival rates were 95.3% (95% confidence interval [CI], 92.0-97.2), 91.1% (95% CI, 86.5-94.2), and 82.9% (95% CI, 75.3-88.4) at 5, 10, and 15 years, respectively. Freedom from postoperative aortic insufficiency (AI) grade ≥ 2 was 84.8% (95% CI, 79.9-88.6) and 74.3% (95% CI, 67.4-79.9) at 5 and 10 years, respectively. Freedom from reintervention for aortic valve disease was 97.1% (95% CI, 94.2-98.5), 92.9% (95% CI, 88.2-95.7), and 92.5% (95% CI, 87.1-95.7) at 5, 10, and 15 years, respectively. Preoperative AI ≥ 2 (hazard ratio, 1.782; 95% CI, 1.352-2.350) and a ventriculoaortic junction ≥ 29 mm (hazard ratio, 3.379; 95% CI, 1.726-6.616) were predictive factors for postoperative AI ≥ 2 in a multivariate analysis (P < .001). CONCLUSIONS: Preoperative AI ≥ 2 and a ventriculoaortic junction ≥ 29 mm were identified as risk factors for late postoperative AI ≥ 2.

Early hyperoxia and 28-day mortality in patients on venoarterial ECMO support for refractory cardiogenic shock: a bicenter retrospective propensity score-weighted analysis.

BACKGROUND: The mortality rate for a patient with a refractory cardiogenic shock on venoarterial (VA) extracorporeal membrane oxygenation (ECMO) remains high, and hyperoxia might worsen this prognosis. The objective of the present study was to evaluate the association between hyperoxia and 28-day mortality in this setting. METHODS: We conducted a retrospective bicenter study in two French academic centers. The study population comprised adult patients admitted for refractory cardiogenic shock. The following arterial partial pressure of oxygen (PaO2) variables were recorded for 48 h following admission: the absolute peak PaO2 (the single highest value measured during the 48 h), the mean daily peak PaO2 (the mean of each day's peak values), the overall mean PaO2 (the mean of all values over 48 h), and the severity of hyperoxia (mild: PaO2 < 200 mmHg, moderate: PaO2 = 200-299 mmHg, severe: PaO2 ≥ 300 mmHg). The main outcome was the 28-day all-cause mortality. Inverse probability weighting (IPW) derived from propensity scores was used to reduce imbalances in baseline characteristics. RESULTS: From January 2013 to January 2020, 430 patients were included and assessed. The 28-day mortality rate was 43%. The mean daily peak, absolute peak, and overall mean PaO2 values were significantly higher in non-survivors than in survivors. In a multivariate logistic regression analysis, the mean daily peak PaO2, absolute peak PaO2, and overall mean PaO2 were independent predictors of 28-day mortality (adjusted odds ratio [95% confidence interval per 10 mmHg increment: 2.65 [1.79-6.07], 2.36 [1.67-4.82], and 2.85 [1.12-7.37], respectively). After IPW, high level of oxygen remained significantly associated with 28-day mortality (OR = 1.41 [1.01-2.08]; P = 0.041). CONCLUSIONS: High oxygen levels were associated with 28-day mortality in patients on VA-ECMO support for refractory cardiogenic shock. Our results confirm the need for large randomized controlled trials on this topic.

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.

Subclavian versus femoral arterial cannulations during extracorporeal membrane oxygenation: A propensity-matched comparison.

BACKGROUND: During peripheral extracorporeal veno-arterial membrane oxygenation (VA-ECMO) support, subclavian arterial cannulation provides, in comparison to femoral arterial cannulation, an anterograde flow which may prevent from left ventricular (LV) distention and improve outcomes. We aimed to compare the effectiveness of subclavian cannulation to femoral cannulation in reducing LV overdistension consequences, hemostatic complications and mortality. METHODS: This retrospective study conducted in two intensive care units of the Lille academic hospitals from January 2013 to December 2019 included 372 non-moribund adult patients supported by VA-ECMO. The primary endpoint was a new onset of pulmonary edema (PO) or LV unloading. Secondary endpoints were myocardial recovery, serious bleeding (according to Extracorporeal Life Support Organization definition), thrombotic complications (a composite of stroke, cannulated limb or mesenteric ischemia, intracardiac or aortic-root thrombosis) and 28 day mortality. Differences in outcomes were analyzed using propensity score matching (PSM) and inverse probability of treatment weighting adjustment (IPTW). RESULTS: As compared to femoral cannulation (n = 320 patients), subclavian cannulation (n = 52 patients) did not reduce the occurrence of new onset of PO or LV unloading after PSM [HR 0.99 (95% CI 0.51-1.91)]. There was no other difference in outcomes in PSM cohort. In IPTW adjustment cohort, subclavian cannulation was associated with reduced recovery and increased serious bleeding with four accidental decannulations observed. CONCLUSION: Subclavian artery cannulation was not associated with reduced LV distension related complications, thrombotic complications and 28 day mortality. Rather, it may increase serious bleeding and accidental decannulations, and reduce recovery. Therefore, subclavian cannulation should be limited to vascular accessibility issues.

Venoarterial Extracorporeal Membrane Oxygenation in Severe Drug Intoxication: A Retrospective Comparison of Survivors and Nonsurvivors.

Selecting patients most likely to benefit from venoarterial extracorporeal membrane oxygenation (V-A ECMO) to treat refractory drug-induced cardiovascular shock remains a difficult challenge for physicians. This study reported short-term survival outcomes and factors associated with mortality in V-A ECMO-treated patients for poisoning. Twenty-two patients placed on V-A ECMO after drug intoxication from January 2014 to December 2020 were retrospectively analyzed. The primary endpoint of this study was survival at hospital discharge. Univariate descriptive analysis was performed to compare survivors and nonsurvivors during hospitalization. The overall survival at hospital discharge was 45.4% (n = 10/22). Survival rate tended to be higher in patients treated for refractory shock (n = 7/10) compared with those treated for refractory cardiac arrest (n = 3/12, p = 0.08). Low-flow duration and time from admission to ECMO cannulation were shorter in survivors ( p = 0.02 and p = 0.03, respectively). Baseline characteristics before ECMO, including the class of drugs involved in the poisoning, between survivors and nonsurvivors were not statistically different except pH, bicarbonate, serum lactate, Sequential Organ Failure Assessment, and Survival After Veno-arterial-ECMO (SAVE) score. All patients with SAVE-score risk classes II/III survived whereas 85.7% (n = 12/14) of those with SAVE-score risk classes IV/V died. A lactic acid >9 mmol/L predicts mortality with a sensitivity/specificity ratio of 83.3%/100%. V-A ECMO for severe drug intoxication should be reserved for highly selected poisoned patients who do not respond to conventional therapies. Shortening the timing of V-A ECMO initiation should be a key priority in improving outcomes. Low-flow time >60min, lactic acid >9mmol/L, and SAVE-score may be good indicators of a worse prognosis.

Evaluation of Anti-Activated Factor X Activity and Activated Partial Thromboplastin Time Relations and Their Association with Bleeding and Thrombosis during Veno-Arterial ECMO Support: A Retrospective Study.

BACKGROUND: We aimed to investigate the relationship between anti-activated Factor X (anti-FXa) and activated Partial Thromboplastin Time (aPTT), and its modulation by other haemostasis co-variables during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. We further investigated their association with serious bleeding and thrombotic complications. METHODS: This retrospective single-center study included 265 adults supported by VA-ECMO for refractory cardiogenic shock from January 2015 to June 2019. The concordance of anti-FXa and aPTT and their correlations were assessed in 1699 paired samples. Their independent associations with serious bleeding or thrombotic complications were also analysed in multivariate analysis. RESULTS: The concordance rate of aPTT with anti-FXa values was 50.7%, with 39.3% subtherapeutic aPTT values. However, anti-FXa and aPTT remained associated (ß = 0.43 (95% CI 0.4-0.45) 10-2 IU/mL, p < 0.001), with a significant modulation by several biological co-variables. There was no association between anti-FXa nor aPTT values with serious bleeding or with thrombotic complications. CONCLUSION: During VA-ECMO, although anti-FXa and aPTT were significantly associated, their values were highly discordant with marked sub-therapeutic aPTT values. These results should favour the use of anti-FXa. The effect of biological co-variables and the failure of anti-FXa and aPTT to predict bleeding and thrombotic complications underline the complexity of VA-ECMO-related coagulopathy.

IMPELLA® or Extracorporeal Membrane Oxygenation for Left Ventricular Dominant Refractory Cardiogenic Shock.

Mechanical circulatory support (MCS) devices are effective tools in managing refractory cardiogenic shock (CS). Data comparing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and IMPELLA® are however scarce. We aimed to assess outcomes of patients implanted with these two devices and eligible to both systems. From 2004 to 2020, we retrospectively analyzed 128 patients who underwent VA-ECMO or IMPELLA® in our institution for refractory left ventricle (LV) dominant CS. All patients were eligible to both systems: 97 patients were first implanted with VA-ECMO and 31 with IMPELLA®. The primary endpoint was 30-day all-cause death. VA-ECMO patients were younger (52 vs. 59.4, p = 0.006) and had a higher lactate level at baseline than those in the IMPELLA® group (6.84 vs. 3.03 mmol/L, p < 0.001). Duration of MCS was similar between groups (9.4 days vs. 6 days in the VA-ECMO and IMPELLA® groups respectively, p = 0.077). In unadjusted analysis, no significant difference was observed between groups in 30-day mortality: 43.3% vs. 58.1% in the VA-ECMO and IMPELLA® groups, respectively (p = 0.152). After adjustment, VA-ECMO was associated with a significant reduction in 30-day mortality (HR = 0.25, p = 0.004). A higher rate of MCS escalation was observed in the IMPELLA® group: 32.3% vs. 10.3% (p = 0.003). In patients eligible to either VA-ECMO or IMPELLA® for LV dominant refractory CS, VA-ECMO was associated with improved survival rate and a lower need for escalation.

Vascular Endothelial Damage in the Pathogenesis of Organ Injury in Severe COVID-19.

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Prognostic value of aerobic capacity and exercise oxygen pulse in postaortic dissection patients.

BACKGROUND: Although recommendations encourage daily moderate activities in post aortic dissection, very little data exists regarding cardiopulmonary exercise testing (CPET) to personalize those patient's physical rehabilitation and assess their cardiovascular prognosis. DESIGN: We aimed at testing the prognostic insight of CPET regarding aortic and cardiovascular events by exploring a prospective cohort of patients followed-up after acute aortic dissection. METHODS: Patients referred to our department after an acute (type A or B) aortic dissection were prospectively included in a cohort between September 2012 and October 2017. CPET was performed once optimal blood pressure control was obtained. Clinical follow-up was done after CPET for new aortic event and major cardio-vascular events (MCE) not directly related to the aorta. RESULTS: Among the 165 patients who underwent CPET, no adverse event was observed during exercise testing. Peak oxygen pulse was 1.46(1.22-1.84) mlO2/beat, that is, 97 (83-113) % of its predicted value, suggesting cardiac exercise limitation in a population under beta blockers (92% of the population). During a follow-up of 39(20-51) months from CPET, 42 aortic event recurrences and 22 MCE not related to aorta occurred. Low peak oxygen pulse (<85% of predicted value) was independently predictive of aortic event recurrence, while low peak oxygen uptake (<70% of predicted value) was an independent predictor of MCE occurrence. CONCLUSION: CPET is safe in postaortic dissection patients should be used to not only to personalize exercise rehabilitation, but also to identify those patients with the highest risk for new aortic events and MCE not directly related to aorta.

Utility of Three-Dimensional Transesophageal Echocardiography for Mitral Annular Sizing in Transcatheter Mitral Valve Replacement Procedures: A Cardiac Computed Tomographic Comparative Study.

BACKGROUND: Three-dimensional (3D) transesophageal echocardiographic (TEE) imaging is frequently used as an initial screening tool in the evaluation of patients who are candidates for transcatheter mitral valve replacement (TMVR). However, little is known about the imaging correlation with the gold standard, computed tomographic (CT) imaging. The aims of this study were to test the quantitative differences between these two modalities and to determine the best 3D TEE parameters for TMVR screening. METHODS: Fifty-seven patients referred to the heart valve clinic for TMVR with prostheses specifically designed for the mitral valve were included. Mitral annular (MA) analyses were performed using commercially available software on 3D TEE and CT imaging. RESULTS: Three-dimensional TEE imaging was feasible in 52 patients (91%). Although 3D TEE measurements were slightly lower than those obtained on CT imaging, measurements of both projected MA area and perimeter showed excellent correlations, with small differences between the two modalities (r = 0.88 and r = 0.92, respectively, P < .0001). Correlations were significant but lower for MA diameters (r = 0.68-0.72, P < .0001) and mitroaortic angle (r = 0.53, P = .0001). Receiver operating characteristic curve analyses showed that 3D TEE imaging had a good ability to predict TMVR screening success, defined by constructors on the basis of CT measurements, with ranges of 12.9 to 15 cm2 for MA area (area under the curve [AUC] = 0.88-0.91, P < .0001), 128 to 139 mm for MA perimeter (AUC = 0.85-0.91, P < .0001), 35 to 39 mm for anteroposterior diameter (AUC = 0.79-0.84, P < .0001), and 37 to 42 mm for posteromedial-anterolateral diameter (AUC = 0.81-0.89, P < .0001). CONCLUSIONS: Three-dimensional TEE measurements of MA dimensions display strong correlations with CT measurements in patients undergoing TMVR screening. Three-dimensional TEE imaging should be proposed as a reasonable alternative to CT imaging in this vulnerable population.

Aortic morphology post type A acute aortic syndrome: Prognosis significance and association with 24-hour blood pressure-monitoring parameters.

BACKGROUND: After an emergent surgery for type A acute aortic syndrome, medical management is based on optimal blood pressure (BP) control. We assessed the prognostic significance of BP monitoring and its relationship with aortic morphology following type A acute aortic syndrome. METHODS: The data of 120 patients who underwent BP monitoring after a type A acute aortic syndrome from January 2005 to June 2016 were retrospectively collected. The first CT angiogram performed after surgery was used for the morphological analysis. RESULTS: The population included 79 males, with an overall mean age of 60 ± 12 years. Seven patients (5.8%) died during a median follow-up of 5.5 years. The median delay between BP monitoring and discharge was 3 (1-5) months. The mean 24-hour BP of the cohort was 127/73 mm Hg ± 10/17. During follow-up, different parameters of BP monitoring were not associated with the risk of aortic events. However, the diameter of the false lumen of the descending thoracic aorta was the best predictor associated with the risk of new aortic events during follow-up, particularly for the threshold of 28 mm or more (P < .001; Hazard ratio 4.7[2.7-8.2]). The diameter of the false lumen was associated with night-time systolic BP (P = .025; r = .2), 24-hour pulse pressure (P = .002; r = .28), and night-time pulse pressure (P = .008; r = .24). CONCLUSION: The risk of new aortic events following type A acute aortic syndrome is associated with the size of the residual false lumen, but not directly with BP parameters. Night-time BP parameters are associated with the size of the residual false lumen.

Active Aortic Endocarditis in Young Adults: Long-term Results of the Ross Procedure.

BACKGROUND: The best valvular substitute remains controversial in young adults with active aortic valve endocarditis. The Ross procedure has gained interest because of its theoretical resistance to infection. We aimed to report our long-term outcomes of the Ross procedure in this indication. METHODS: Between March 1992 and January 2019, 511 patients underwent a Ross procedure in our institution. Among them, we included 38 patients who suffered from an active aortic valve infective endocarditis. The mean age was 33.9 ± 8.1 years. Six patients had emergent procedures and 17 patients had perivalvular involvement. A pulmonary autograft was implanted using the full root technique in 78.9% of patients. Median follow-up was 12 (interquartile range, 1.75-16.25) years. RESULTS: The hospital mortality rate was 5.3%. Estimated overall survival was 84.2% ± 6.6% at 10 years. There were 2 cases of recurrent endocarditis, both requiring reoperation. Six other patients required reoperation on an autograft or homograft. Estimated freedom from recurrent endocarditis or reoperation was 89.4% ± 5.9% at 10 years. CONCLUSIONS: In experienced centers, the Ross procedure is a reliable alternative to prosthetic or homograft valve replacement in young adults experiencing active aortic valve endocarditis, with a low operative risk and good long-term results.

Transcatheter mitral valve replacement: factors associated with screening success and failure.

AIMS: Transcatheter mitral valve replacement (TMVR) is a promising therapeutic solution to treat high-risk patients with severe mitral regurgitation (MR) contraindicated to surgery. Optimal selection of patients who will benefit from the procedure is of paramount importance. We aimed to investigate factors associated with TMVR screening. METHODS AND RESULTS: From November 2016 to July 2018, we examined conditions associated with TMVR screening success in patients referred to the two French heart valve clinics with the greatest TMVR experience. Among a total of 40 consecutively screened patients, 16 (40%) were selected for TMVR (8 Twelve Intrepid, 7 Tendyne and 1 HighLife), while 24 patients (60%) were refused for TMVR mainly because of a too large mitral annulus (MA) (n=15, 62% of those refused), or too small anatomy and risk of neo-left ventricular outflow tract (LVOT) obstruction (n=6, 25% of those refused). Patients with suitable anatomy for TMVR were more often male and more frequently suffered from secondary MR (p=0.01) associated with previous myocardial infarction and presented a commissure-to-commissure diameter less than 39 mm (AUC=0.72, p=0.0085) and LVESD greater than 32 mm (AUC=0.83, p<0.0001) on transthoracic echocardiography, and an MA area less than 17.6 cm² (AUC=0.95, p<0.0001) and anteroposterior diameter greater than 41.6 mm (AUC=0.87, p<0.001) on CT scan. CONCLUSIONS: Despite several prostheses being available, most patients referred to heart valve clinics who are good candidates with regard to their clinical profile cannot have TMVR because of mismatch between their anatomy and prosthesis characteristics. Our findings suggest the need to develop new prostheses adapted to larger mitral annuli but with a lower impact on the LVOT.

Arterial Pulsatility and Circulating von Willebrand Factor in Patients on Mechanical Circulatory Support.

BACKGROUND: The main risk factor for bleeding in patients with continuous-flow mechanical circulatory support (CF-MCS) is the acquired von Willebrand factor (VWF) defect related to the high shear-stress forces developed by these devices. Although a higher bleeding rate has been reported in CF-MCS recipients who had reduced pulsatility, the relation between pulsatility and the VWF defect has never been studied. OBJECTIVES: The purpose of this study was to investigate the relation between pulsatility and VWF under CF-MCS. METHODS: We assessed the effect of 2 CF-MCS on VWF multimer degradation in a mock circulatory loop (model 1). Using these devices, we investigated in a dose-effect model (model 2) 3 levels of pulsatility in 3 groups of swine. In a cross-over model (model 3), we studied the effects of sequential changes of pulsatility on VWF. We reported the evolution of VWF multimerization in a patient undergoing serial CF-MCS and/or pulsatile-MCS. RESULTS: We demonstrated the proteolytic degradation of VWF multimers by high shear CF-MCS in a circulatory loop without pulsatility. We observed both in swine models and in a patient that the magnitude of the VWF degradation is modulated by the pulsatility level in the high shear-stress level condition, and that the restoration of pulsatility is a trigger for the endothelial release of VWF. CONCLUSIONS: We demonstrated that the VWF defect reflects the balance between degradation induced by the shear stress and the endothelial release of new VWF triggered by the pulsatility. This modulation of VWF levels could explain the relationship between pulsatility and bleeding observed in CF-MCS recipients. Preservation of pulsatility may be a new target to improve clinical outcomes of patients.

Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement.

BACKGROUND: Postprocedural aortic regurgitation occurs in 10 to 20% of patients undergoing transcatheter aortic-valve replacement (TAVR) for aortic stenosis. We hypothesized that assessment of defects in high-molecular-weight (HMW) multimers of von Willebrand factor or point-of-care assessment of hemostasis could be used to monitor aortic regurgitation during TAVR. METHODS: We enrolled 183 patients undergoing TAVR. Patients with aortic regurgitation after the initial implantation, as identified by means of transesophageal echocardiography, underwent additional balloon dilation to correct aortic regurgitation. HMW multimers and the closure time with adenosine diphosphate (CT-ADP), a point-of-care measure of hemostasis, were assessed at baseline and 5 minutes after each step of the procedure. Mortality was evaluated at 1 year. A second cohort (201 patients) was studied to validate the use of CT-ADP in order to identify patients with aortic regurgitation. RESULTS: After the initial implantation, HMW multimers normalized in patients without aortic regurgitation (137 patients). Among the 46 patients with aortic regurgitation, normalization occurred in 20 patients in whom additional balloon dilation was successful but did not occur in the 26 patients with persistent aortic regurgitation. A similar sequence of changes was observed with CT-ADP. A CT-ADP value of more than 180 seconds had sensitivity, specificity, and negative predictive value of 92.3%, 92.4%, and 98.6%, respectively, for aortic regurgitation, with similar results in the validation cohort. Multivariable analyses showed that the values for HMW multimers and CT-ADP at the end of TAVR were each associated with mortality at 1 year. CONCLUSIONS: The presence of HMW-multimer defects and a high value for a point-of-care hemostatic test, the CT-ADP, were each predictive of the presence of aortic regurgitation after TAVR and were associated with higher mortality 1 year after the procedure. (Funded by Lille 2 University and others; ClinicalTrials.gov number, NCT02628509.).