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Remarkable progress has been made in the pharmacological management of patients with cardiovascular disease, including the frequent use of antithrombotic agents. Nonetheless, bleeding complications remain frequent and potentially life-threatening. Therapeutic interventions relying on prompt antithrombotic drug reversal or removal have been developed to assist clinicians in treating patients with active bleeding or an imminent threat of major bleeding due to urgent surgery or invasive procedures. Early phase studies on these novel strategies have shown promising results using surrogate pharmacodynamic endpoints. However, the benefit of reversing/removing antiplatelet or anticoagulant drugs should always be weighed against the possible prothrombotic effects associated with withdrawal of antithrombotic protection, bleeding, and surgical trauma. Understanding the ischemic-bleeding risk tradeoff of antithrombotic drug reversal and removal strategies in the context of urgent high-risk settings requires dedicated clinical investigations, but challenges in trial design remain, with relevant practical, financial, and ethical implications.

Background Percutaneous left atrial appendage closure (LAAC) has emerged as a valid option for prevention of thromboembolic events in patients with non-valvular atrial fibrillation and contraindications for oral anticoagulation. The most recent devices have been created to improve the intervention efficiency and to allow the procedure in a wider range of anatomies. The new-generation Watchman FLX (WMFLX) features a new design but its in vivo performances have not been compared to the previous WATCHMAN 2.5 (WM2.5) prosthesis. Hence, the data regarding conformability, compression and device-related LAA remodeling are scarce. Purpose To compare the anatomical results of WM2.5 and WMFLX implantation and impact on LAA dimensions. Methods This study included LAAC patients from the WATCH-DUAL registry who benefited from a pre- and post-intervention CT scan. The WATCH-DUAL study was a dual center observational study including all the LAAC procedures prospectively collected in local registries from two high-volume centres between November 2017 and December 2020. The LAA and device dimensions were measured in a centralized core lab by 3D CT scan reconstruction methods, focusing on the device landing zone (LZ/defined as the cross section of the appendage that was perpendicular to its axis and connected the circumflex artery to a point 1 to 2 cm inside the LAA). Results This analysis included n=107 patients (n=58 WMFLX, n=49 WM2.5). The patients clinical profiles didn't differ, except for a higher proportion of coronary artery disease in WM2.5 group. The LAA dimensions were comparable between groups. There was a significantly higher proportion of chickenwing shapes in the WMFLX patients. The mean device baseline diameter was in the WMFLX compared to the WM2.5 patients (28.8±0.5 vs. 25.7±0.4 mm, p The median delay for CT control was 48 (43–62) days. The LZ area (451 (363–521) vs. 366 (260–459) mm2, p A multivariable regression analysis demonstrated that baseline LAA length, baseline LZ eccentricity and WM FLX use were independent predictors of LAA remodeling/dimensions increase. Conclusion LAA dimensions increased over time at the site of WM prosthesis implantation suggesting a local positive appendage remodeling after procedure. This phenomenon appears to be more pronounced with the WMFLX device. Funding Acknowledgement Type of funding sources: None.

Background Bicuspid aortic valves (BAV) represent the main cause of severe dystrophic aortic insufficiency in young patients and are mostly replaced with high rates of valve-related events and altered quality of life in case of mechanical prosthesis. Valve repair is now recommended for root aneurysm and tricuspid aortic valves (TAV) when feasible. However, concerns remain regarding the long-term durability of BAV repair, compared to TAV. Purpose Our objective is to compare the long-term results of repair between TAV and BAV, in consecutive patients operated on with a standardized approach according to each phenotype of the dystrophic ascending aorta. Methods Data were prospectively collected into the multicenter international AVIATOR registry (AorticValve repair InternATiOnal Registry). Between 2003 and 2019, according to ascending aorta phenotypes, 226 patients with BAV and 309 patients with TAV underwent either isolated valve repair with external ring annuloplasty (26,2%), or root remodeling with external ring (59,4%), or a supra-coronary graft with external ring (14,4%). Results Cusp repair was performed in 95,1% patients in the BAV group and in 63,8% in the TAV group. The 30-day operative mortality was 0,93% (n=5). Mean follow-up was 5,5±4,4 years. The actuarial survival rate at 12 years was 93,2% in the BAV group and 87,8% in the TAV group (p=0,14). Freedom from reoperation at 12 years was similar between groups being 94,9% for bicuspid and 93,2% for tricuspid (p=0,75). Freedom from major adverse valve-related events at 12 years was 82,8% and 82,9% in BAV and TAV groups respectively (p=0,17). At 12 years, freedom from AI ≥Grade 2 or ≥Grade 3 was 68,7% and 94,3% for BAV and 76,5% and 94,7% for TAV group, with no significant difference (respectively p=0,16 and p=0,92). Conclusion Aortic valve repair with a standardized approach adapted to the aorta phenotype provides excellent long-term results with a low rate of valve-related events. Similar results were achieved between BAV and TAV patients. freedom from reoperation for BAV and TAV Funding Acknowledgement Type of funding source: None

Background The recent expert consensus of the EAPCI suggested OCT criteria for the optimization of PCT after stent implantation. Using the data from the randomized, controlled DOCTORS study, we aimed to analyze the proportion of OCT criteria that were met immediately after stent implantation, and to evaluate the changes made to the revascularization strategy in order to optimize the procedure. Methods The DOCTORS study population consisted of patients admitted for non ST elevation myocardial infarction (NSTEMI) and presenting an indication for PCI with stent implantation of the target lesion. In the 120 patients randomized to the OCT-guided group, OCT was performed after initial coronary angiography and repeated immediately after stent implantation. The operator was required to evaluate quantitative measures of the reference diameter and reference area of the vessel and the length of the lesion based on the OCT images acquired before PCI. All OCT images were analyzed in a centralized core laboratory by 2 independent operators blinded to the angiographic findings. Post-PCI optimization targets to be achieved following stent implantation included optimal stent expansion (minimal stent area (MSA)/average reference lumen >80%), avoidance of landing zone in plaque burden >50% or lipid rich tissue; avoidance of large malapposition regions (axial distance Results Among the 120 patients who had an OCT run performed immediately after stent implantation, 50 patients (42%) had stent under-expansion, 59 (49%) had landing zone in plaque burden >50% or lipid rich tissue, 27 (22.5%) had stent malapposition, 25 (20.8%) had extensive irregular tissue protrusion and 45 (37.5%) had extensive edge dissection. Only 2 patients (1.7%) fullfiled all criteria of post-PCI optimization immediately after stent implantation, while no criterion was reached in 15 patients (12.5%). Post-stent overdilation was performed in all patients with stent underexpansion, and in 22/27 patients (81.5%) with stent malapposition. Additional stent implantation was performed in 32 patients (24 for landing zone in plaque burden >50% and 8 for extensive adventitial edge dissection). Overall, the use of OCT led the operator to optimize the procedural strategy in 60 patients (50%). Conclusion The proportion of suboptimal results as evaluated by OCT and based on the EAPCI criteria immediately after stent implantation was very high in the DOCTORS study, even though the choice of stent in these patients was based on pre-PCI OCT data. The post-PCI OCT findings led to a change of strategy to optimize the procedure in 50% of patients. It remains to be determined through a larger prospective study whether this optimization of PCI strategy is associated with a clinical benefit in the long term.

Background Quantitative flow reserve (QFR) is a computation of fractional flow reserve (FFR) based on angiography without use of a pressure wire. The ability to predict post-PCI FFR using residual QFR after virtual stenting (pre-PCI), and using QFR (post-PCI) remains unknown. We sought to evaluate the correlation and diagnosis accuracy of residual QFR and post-PCI QFR to predict post-PCI FFR. Methods From the DOCTORS (Does Optical Coherence Tomography Optimize Results of Stenting) study population, we blindly analyzed the following from angiography, and compared them to post-PCI FFR: pre-PCI residual contrast QFR (cQFR) and fixed QFR (fQFR), and post-PCI cQFR and fQFR. Results 93 post-PCI QFR measurements and 84 residual QFR measurements were compared to post-PCI FFR measurements in 93 patients. Compared to the post-PCI FFR mean value of 0.92±0.05, mean values of residual cQFR, residual fQFR, post-PCI cQFR and post-PCI fQFR were, respectively: 0.94±0.05, 0.93±0.05, 0.93±0.06 and 0.93±0.05 (p values >0.05 for all pairs except for residual cQFR versus FFR (p=0.01)). Pearson correlation coefficients of residual cQFR, residual fQFR, post-PCI cQFR and post-PCI fQFR compared with post-PCI FFR were, respectively: 0.62, (95% CI: 0.46–0.73); 0.61, (95% CI: 0.45–0.73); 0.75, (95% CI: 0.64–0.83) and 0.73, (95% CI: 0.62–0.81). Area under the curves for these indices with a post-PCI FFR cutoff value of 0.90 were, respectively: 0.79, 0.78, 0.85 and 0.84. Conclusions cQFR and fQFR correlated well and had similar diagnostic performance. Pre-PCI QFR analysis with virtual PCI, and post-PCI QFR analysis, correlated well with post-PCI FFR, and had similar diagnostic accuracy. Further studies are needed to prospectively validate a QFR-guided PCI strategy.

Background Percutaneous left atrial appendage occlusion (LAAO) has emerged as a valid alternative to oral anticoagulation therapy for the prevention of systemic embolism in patients with non-valvular atrial fibrillation (AF). Microvesicles (MVs) are shed-membrane particles generated during various cellular types activation/ apoptosis that carry out diverse biological effects, including procoagulant effects. Left atrial appendage has been suspected to be a potential source of MVs during AF, but the effects of LAAO on MVs production and circulating levels are unknown.The aim of this work study was to assess the variations of circulating MVs levels following LAAO. Methods The study includedn=25 LAAO patients and n=25 control patients who underwent coronary angiography. LAAO and control patients were treated by clopidogrel+ aspirin loading doses before procedures. Blood samples were drawn before antiplatelets therapy & 2 days after for all. A third sample was collected 6 weeks after procedure in LAAO patients. In N=10 extra patients, blood samples were collected from right atrium, left appendage and pulmonary vein during LAAO procedure. Circulating procoagulant (AnnV+), endothelial (CD62e+), platelets (CD41+), red blood cells/RBC (CD235+), leukocytes (CD11+) derived-MVs were measured using flow cytometry methods. Results Control and LAAO groups baseline characteristics were comparable, except for the higher age & incidence of previous stroke and lower incidence of coronary artery disease in LAAO patients. Baseline levels of the different microvesicles were comparable in both groups. In the LAAO group, we observed a significant increase of AnnV+ MVs (4355 [1712–8478] vs. 1798 [1006–2759] ev/μL, p=0.001), platelets (1615 [833–4772] vs. 802 [358–1376] ev/, p=0.005), RBC (207 [85–708] vs. 35 [5–84] ev/μL, p Conclusions LAAO impact circulating MVs and could create mild pro-coagulant status, inflammation and potential erythrocytes activation due to device presence during the first 6 weeks following intervention. These results suggest that careful attention should be paid in the anti-platelet/anti-coagulant therapy in the post procedural course. Acknowledgement/Funding This work was funded by a research grant from the French Society of Cardiology and a research grant from St Jude/Abbott

This editorial refers to ‘Circulating CD31+/Annexin V+ microparticles correlate with cardiovascular outcomes’[†][1], by J.-M. Sinning et al. , on page 2034 Despite significant advances in medical and interventional management during the past decades, coronary artery disease (CAD) and its consequences, which include myocardial infarction, sudden cardiac death, and chronic cardiac failure, remain a major contributor to mortality in western countries. Lifestyle modifications and secondary prevention medications, such as statins or angiotensin-converting enzyme (ACE) inhibitors, have improved outcome, but some patients still experience adverse cardiovascular events as a consequence of a particular atherosclerotic disease evolution. Identification of these high-risk, vulnerable patients remains a challenging issue.1 Atherosclerosis is a systemic disease characterized by endothelial dysfunction and by local and general inflammation. It is aggravated by platelet activation, and its ultimate evolution is plaque rupture and thrombosis.2 Identification of vulnerable plaques cannot be achieved by conventional angiography and requires sophisticated and invasive investigations such as intravascular ultrasound, optical coherence tomography, or magnetic resonance imaging.1 Moreover, there is no real consensus regarding a simple definition of vulnerable plaque. Risk stratification of patients based on measurement of circulating biomarkers [high sensitivity C-reactive protein, soluble lipoprotein phospholipase A2, B-type natriuretic peptide (BNP), etc.] or non-invasive evaluation of vascular structure or function (carotid intima-media thickness, flow-mediated dilation, etc.) appear to be more efficient tools in many respects.1 However, none of the above-cited parameters appears to be perfectly appropriate in view of the required criteria (sensitivity, specificity, … [1]: #fn-2

Objective To examine the relation of endothelial microparticles (EMPs) with cardiometabolic risk in the community. Background Circulating EMPs are small membrane vesicles released after endothelial cell injury. Endothelial microparticles are reportedly increased among individuals with a high burden of cardiovascular risk factors. However, prior investigations have been limited to small, highly selected samples. Methods We studied 844 individuals without a history of cardiovascular disease in the Framingham Offspring cohort (mean age 66 ± 9 years, 57% women). We used standardized flow cytometry methods to identify and quantify circulating CD144+ and CD31+/CD41− EMPs. We then used multivariable regression analyses to investigate the relations of EMP phenotypes with cardiovascular and metabolic risk factors. Results In multivariable analyses, the following cardiovascular risk factors were associated with one or more of the circulating EMP populations: hypertension ( P = 0.025 for CD144+,), elevated triglycerides ( P = 0.002 for CD144+, P < 0.0001 for CD31+/CD41−), and metabolic syndrome ( P < 0.0001 for CD144+,). Overall, each tertile increase in the Framingham risk score corresponded to a 9% increase in log-CD31+/CD41− EMPs ( P = 0.022). Furthermore, the presence of hypertriglyceridaemic waist status was associated with 38% higher levels of CD144+ EMPs ( P < 0.0001) and 46% higher levels of CD31+/CD41− EMPs ( P < 0.0001). Conclusion In a large community-based sample, circulating EMP levels were associated with the presence of cardiometabolic risk factors, particularly dyslipidaemia. These data underscore the potential influence of high-risk metabolic profiles on endothelial integrity.

A 75-year-old man was referred to our institution for lateral ST-elevation myocardial infarction. He previously underwent a 2.5 × 18 mm sirolimus-eluting stent implantation on the first diagonal branch 9 years earlier for symptomatic stable coronary artery disease. He has been under aspirin for the past 8 years with an uneventful evolution. Thrombolysis, clopidogrel-loading …

Purpose: Thrombus aspiration (TA) is recommended in patients with ST segment elevation myocardial infarction (STEMI) to improve myocardial perfusion during percutaneous coronary intervention (PCI). However, the angiographic assessment of residual thrombotic burden following TA has several inaccuracies. Optical coherence tomography (OCT) allows excellent discrimination between the thrombotic and atherosclerotic plaque components. We assessed the feasibility of quantification of residual thrombotic burden by OCT and its relation to angiographic results of TA. Methods: Patients with acute STEMI (symptoms onset ≤ 12 hours) who underwent TA were screened for inclusion. OCT was performed in patients with successful TA (TIMI flow=3+ chest pain cessation+ ST elevation resolution). Culprit lesion was analyzed by quantitative coronary angiography (QCA) and TIMI flow was measured before and after TA. Thrombus surface, thrombus length, thrombotic score, minimal luminal area (MLA) and cross sectional area (CSA) were quantified by serial area measurement within the athero-thrombotic culprit lesion in 1 mm intervals. The absolute residual thrombotic volumes (absThV) and thrombotic volume indexed to artery volume (indThV) were then calculated. Results: A total of 30 patients were included in the study (mean age: 58.4±3 y; 77% men; 47% anterior localization). OCT was feasible in all cases and did not induce any complication (including embolization, artery re-occlusion or dissection). Residual thrombotic material was present in all cases, irrespective of the angiographic result: the residual absThV, indThV and thrombotic score were respectively 19.8±4.3 mm3, 45.9±8.2% and 23.7±3.3. AbsThV and indThV highly correlated to the values of thrombotic score (respectively r=0.86 and 0.79, p70%) result. We didn't observe any significant difference in the thrombus characteristics between the two groups, confirming that QCA accuracy for prediction of thrombus burden in STEMI is limited. Conclusion: OCT can be safely performed in patients presenting with STEMI treated with primary PCI and allows quantification of residual thrombotic material. A significant discrepancy remains between angiographic result of TA and OCT data.

Purpose: Intra-aortic balloon pump (IABP) is increasingly used among patients with end-stage heart failure (HF) but its efficacy in successfully bridging candidates to heart transplantation (HTx) and effective transplant benefit of patients receiving IABP are unexplored. Herein we compare success rate in achieving HTx and post-transplant survival between transplant candidates who needed IABP support and those stabilized with medical therapy. Methods: All HTx candidates followed between 1998 and 2012 were eligible for this retrospective study. Outcome events were: transplant, death/deterioration while on waiting list, improved and excluded from transplant program. Kaplan Meyer method was used to analyze the occurrence of events. Results: Out of 585 patients included, 35 (6%) needed IABP while 550 (94%) could be managed by medical therapy alone. Mean age was similar in the two groups (50.8±13.5 vs. 50.3±14.4 ys). As expected, need for IABP identified patients at significantly higher risk for mortality (estimated 2-year death rate: 30±3% vs 55±20%, p < 0.01). Of note IABP in progressive deteriorating chronic HF showed 100% mortality rate 3 months after support placement, whereas those who needed IABP for acute HF as initial presentation had 10% death rate during the same span of time. Thanks to listing prioritization, succes rate in achieving HTX in IABP patients was similar to medically treated, with about 80% of patients transplanted in both groups. Importantly, ten-year estimated post-transplant survival was similar in the two groups (68±3 vs. 60±15%, p=0.8; Figure 1). ![Figure][1] Figure 1. Post-transplant survival: IABP vs. noIABP Conclusions: Need for IABP identifies very high mortality risk, in particular for chronic decompensated candidates, but it is a successful strategy as a bridge to HTx and does not limit long-term survival after transplant. [1]: pending:yes

Aims: Time-domain optical coherence tomography (TD-OCT) allows assessment of the anatomy and features of unstable coronary artery lesions, including discrimination between the thrombotic and atherosclerotic plaque components. We sought to investigate the feasibility of thrombus quantification and its monitoring in patients with high thrombotic burden acute coronary syndromes (ACS). Methods: Patients were suitable for inclusion if they presented with an ACS that was successfully revascularized by manual thrombo-aspiration with a residual large thrombus burden on coronary angiography and initial TD-OCT analysis. These patients underwent a second procedure with TD-OCT analysis after several days of optimal anti-thrombotic therapy and benefited eventually from an intra-coronary stent. Coronary lesion stenosis degree was determined by quantitative coronary angiography (QCA). TD-OCT analysis included measurement of thrombus score (as defined by ESC consensus document), thrombus volume, length and minimal luminal area (MLA), which were quantified by serial area measurement within the athero-thrombotic culprit lesion. Results: Seventeen patients fulfilled inclusion criteria. The OCT image quality was suitable for thrombus quantification in n=14 subjects (86% men/ age=57.9±4.5y/ 93% STEMI). Low molecular weight heparin anticoagulation and dual antiplatelet therapy were given to all patients between the two procedures (mean delay: 3.9.±0.3 days). No adverse events were observed during study time. The values of thrombus score and thrombus volume among individuals highly correlated together rho= 0.8, p

Beta blockers are often considered to be less effective for blood pressure control in elderly patients with essential hypertension than calcium antagonists. We therefore compared the efficacy and tolerability of the new beta blocker bisoprolol with those of nifedipine. Fifty-nine patients over 60 years of age with essential hypertension (supine diastolic blood pressure, DBP: 95-115 mmHg) took part in a randomized double-blind study. After 14 days on placebo the patients received either 10 mg bisoprolol o.d. or 20 mg nifedipine SR b.i.d. for 4 weeks. The doses were doubled in patients whose DBP remained greater than 90 mmHg, for a further 4 week period. Blood pressure was measured about 24 hours after bisoprolol and about 12 hours after nifedipine administration. Fifty-six patients were available for efficacy analysis. After 4 weeks there was a distinct decrease of SBP and DBP in both groups (bisoprolol: -22 +/- 16; -15 +/- 9 mmHg; nifedipine: -24 +/- 17; -17 +/- 7 mmHg) with no significant difference between the treatments. DBP was normalized in 22/28 (79%) patients on bisoprolol and in 24/28 (86%) patients on nifedipine (bisoprolol vs nifedipine: NS). There were 7/29 bisoprolol and 14/30 nifedipine patients who experienced at least one side-effect. Overall the tolerability of bisoprolol was considered to be better than that of nifedipine (P = 0.043). In conclusion, bisoprolol 10-20 mg o.d. proved to be as equally effective as nifedipine SR 20-40 mg b.i.d. for the treatment of essential hypertension in the elderly.