Non-pulmonary vein triggers in nonparoxysmal atrial fibrillation: Implications of pathophysiology for catheter ablation.

Rhythm control of persistent atrial fibrillation (AF) patients represents a challenge for the modern interventional cardiac electrophysiologist; as a matter of fact, there is still divergence regarding the best ablative approach to adopt in this population. Different investigational endpoints, variability of techniques and tools, significant technological evolution, and the lack of universally accepted pathophysiological models engendered a considerable heterogeneity in terms of techniques and outcomes, so much that the treatment of persistent subtypes of AF commonly still relies mainly on pulmonary vein (PV) isolation. The purpose of the present review is to report the current experimental and clinical evidence supporting the importance of mapping and ablating non-PV triggers and describe our institutional approach for the ablation of nonparoxysmal AF.

Case report and systematic review of pulmonary embolism mimicking ST-elevation myocardial infarction.

BACKGROUND: To study trends in the clinical presentation, electrocardiograms, and diagnostic imaging in patients with pulmonary embolism presenting as ST segment elevation. METHODS: We performed a systematic literature search for all reported cases of pulmonary embolism mimicking ST-elevation myocardial infarction. Pre-specified data such as clinical presentation, electrocardiogram changes, transthoracic echocardiographic findings, cardiac biomarkers, diagnostic imaging, therapy, and outcomes were collected. RESULTS: We identified a total of 34 case reports. There were 23 males. Mean age of the population was 56.5 ± 15.5 years. Patients presented with dyspnea (76.4%), chest pain (63.6%), and tachycardia (71.4%). All patients presented with ST-elevations, with the most common location being in the anterior-septal distribution, lead V3 (74%), V2 (71%), V1 (62%) and V4 (47%). ST-segment elevations in the inferior distribution were present in lead II (12%), III (18%), and aVF (21%). Presentation was least likely in the lateral distribution. Troponin was elevated in 78.9% of cases. Right ventricular strain was the most common echocardiographic finding. Over 80% of patients had findings consistent with elevated right ventricular pressure, with 50% reported RV dilatation and 20% RV hypokinesis. The most commonly used imaging modality was contrast-enhanced pulmonary angiography. There was a greater incidence of bilateral compared to unilateral pulmonary emboli (72.4% vs. 10%). About 65% patients received anticoagulation and 36.3% were treated with thrombolytics. Forty-six percent of patients required intensive care and 18.7% intubation. Overall mortality was 25.8%. CONCLUSIONS: A review of the literature reveals that in patients presenting with pulmonary embolism, electrocardiogram findings of ST-segment elevations will occur predominantly in the anterior-septal distribution.

Catheter ablation of ventricular tachycardia in nonischemic cardiomyopathy: A propensity score-matched analysis of in-hospital outcomes in the United States.

INTRODUCTION: Monomorphic ventricular tachycardia (VT) is an important cause of morbidity and mortality. Use and outcome data of catheter ablation for VT in nonischemic cardiomyopathy (NICM) are limited. METHODS AND RESULTS: We obtained data from the 2003-2014 National Inpatient Sample databases. We used propensity score matching to compare patients undergoing catheter ablation versus medical therapy of VT related to NICM, and described the temporal trends in utilization and in-hospital outcomes of catheter ablation of VT in patients with NICM in the United States. From 2003 to 2014, of 133,529 patients hospitalized with the principal diagnosis of VT in NICM, 14,651 (11.0%) underwent catheter ablation. In this period, there was an increasing trend in utilization of catheter ablation (9.3% in 2003-2004 to 12.1% in 2003-2014, adjusted OR [per year], 1.12; 95% CI, 1.08-1.16; Ptrend  < 0.001). After propensity score matching, in-hospital mortality occurred in 172 of 14,318 (1.2%) patients in the catheter ablation group, compared with 297 of 14,156 (2.1%) of patients undergoing medical therapy (47% lower; 43% relative difference [adjusted OR, 0.53; 95% CI, 0.43-0.66]). CONCLUSIONS: In patients with NICM, catheter ablation of VT is associated with lower in-hospital mortality compared with those managed medically. The utilization rates of CA for VT related to NICM have increased in the past decade. Adequately powered randomized trials will be necessary to confirm these findings.

Comparison of local versus general anesthesia in patients undergoing transcatheter aortic valve replacement: A meta-analysis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is typically performed under general anesthesia (GA). However, there is increasing data supporting the safety of performing TAVR under local anesthesia/conscious sedation (LA). We performed a meta-analysis to gain better understanding of the safety and efficacy of LA versus GA in patients with severe aortic stenosis undergoing TAVR. METHODS AND RESULTS: We comprehensively searched EMBASE, PubMed, and Web of Science. Effect sizes were summarized using risk ratios (RRs) difference of the mean (DM), and 95% CIs (confidence intervals) for dichotomous and continuous variables respectively. Twenty-six studies and 10,572 patients were included in the meta-analysis. The use of LA for TAVR was associated with lower overall 30-day mortality (RR, 0.73; 95% CI, 0.57-0.93; P = 0.01), use of inotropic/vasopressor drugs (RR, 0.45; 95% CI, 0.28-0.72; P < 0.001), hospital length of stay (LOS) (DM, -2.09; 95% CI, -3.02 to -1.16; P < 0.001), intensive care unit LOS (DM, -0.18; 95% CI, -0.31 to -0.04; P = 0.01), procedure time (DM, -25.02; 95% CI, -32.70 to -17.35; P < 0.001); and fluoroscopy time (DM, -1.63; 95% CI, -3.02 to -0.24; P = 0.02). No differences were observed between LA and GA for stroke, cardiovascular mortality, myocardial infarction, permanent pacemaker implantation, acute kidney injury, paravalvular leak, vascular complications, major bleeding, procedural success, conduction abnormalities, and annular rupture. CONCLUSION: Our meta-analysis suggests that use of LA for TAVR is associated with a lower 30-day mortality, shorter procedure time, fluoroscopy time, ICU LOS, hospital length of stay, and reduced need for inotropic support.

Long-term outcomes of different ablation strategies for ventricular tachycardia in patients with structural heart disease: systematic review and meta-analysis.

Aims: To compare the long-term outcomes of standard ablation of stable ventricular tachycardia (VT) vs. substrate modification, and of complete vs. incomplete substrate modification in patients with structural heart disease (SHD) presenting with VT. Methods and results: An electronic search was performed using major databases. The main outcomes were a composite of long-term ventricular arrhythmia (VA) recurrence and all-cause mortality of standard ablation of stable VT vs. substrate modification, and long-term VA recurrence in complete vs. incomplete substrate modification. Six studies were included for the comparison of standard ablation of stable VT vs. substrate modification, with a total of 396 patients (mean age 63 ± 10 years, 87% males), and seven studies were included to assess the impact of extensive substrate modification, with a total of 391 patients (mean age 64 ± years, 90% males). More than 70% of all the patients included had ischaemic cardiomyopathy. Substrate modification was associated with decreased composite VA recurrence/all-cause mortality compared to standard ablation of stable VTs [risk ratio (RR) 0.57, 95% confidence interval (CI) 0.40-0.81]. Complete substrate modification was associated with decreased VA recurrence as compared to incomplete substrate modification (RR 0.39, 95% CI 0.27-0.58). Conclusion: In patients with SHD who had VT related mainly to ischaemic substrates, there was a significantly lower risk of the composite primary outcome of long-term VA recurrence and all-cause mortality among those undergoing substrate modification compared to standard ablation. Long-term success is improved when performing complete substrate modification.

Benefit of left atrial appendage electrical isolation for persistent and long-standing persistent atrial fibrillation: a systematic review and meta-analysis.

Aims: The long-term outcomes of left atrial appendage electrical isolation (LAAEI) in patients with non-paroxysmal atrial fibrillation (AF) have corroborated the significant role of the LAA in this arrhythmia. We sought to investigate the incremental benefit of LAAEI in patients undergoing catheter ablation for persistent AF or long-standing persistent AF (LSPAF). Methods and results: A systematic review of Medline, Cochrane, and Embase for all the clinical studies in which assessment LAAEI in non-paroxysmal AF patients was performed. The benefit of LAAEI in patients with AF was analysed from seven studies that enrolled a total of 930 patients [mean age 63 ± 5 years; male: 69%]. All studies included patients with either persistent AF or LSPAF or the combination of them. The overall freedom from all-arrhythmia recurrence at 12 months of follow-up off antiarrhythmic medications in patients who underwent LAAEI was 75.5% vs. 43.9% in those in whom only standard ablation was performed [56% relative reduction and 31.6% absolute reduction; risk ratio (RR) 0.44, 95% confidence interval (95% CI) 0.31-0.64; P < 0.0001]. The rate of ischaemic stroke in the LAAEI group was 0.4% and in the control group 2.1% at 12 months follow-up (RR 0.40, 95% CI 0.12-1.30; P = 0.13). Acute complications rates were identical between groups [LAAEI 5.5%, control 5.5% (RR 0.99, 95% CI 0.46-2.16; P = 0.99)]. Conclusion: Left atrial appendage electrical isolation in addition to standard ablation appears to have a substantial incremental benefit to achieve freedom from ALL atrial arrhythmias in patients with persistent AF and LSPAF without increasing acute procedural complications and without raising the risk of ischaemic stroke.

Bivalirudin versus heparin in patients undergoing percutaneous transcatheter aortic valve interventions: A systematic review and meta-analysis.

BACKGROUND: Bivalirudin may be an effective anticoagulation alternative to heparin as anticoagulant agent in percutaneous transcatheter aortic valve interventions (PAVI). We aimed to compare safety and efficacy of bivalirudin versus heparin as the procedural anticoagulant agent in patients undergoing PAVI. METHODS: We conducted an electronic database search of all published data. The primary efficacy endpoints were all-cause mortality, cardiovascular mortality, myocardial infarction, and stroke. Safety endpoints include major and life-threatening bleed according to VARC and BARC bleeding, blood transfusion, vascular complications, and acute kidney injury. Odds ratios (OR) and 95% confidence intervals (CI) computed using the Mantel-Haenszel method. RESULTS: Three studies (n = 1690 patients) were included, one randomized trial and two observational studies. There was a significant difference favoring bivalirudin over heparin for myocardial infarction (OR 0.41, 95%CI 0.20-0.87). There was no significant difference in all-cause mortality at 30 days (OR 0.97, 95%CI 0.62-1.52), cardiovascular mortality (OR 1.03, 95%CI 0.52-2.05), stroke (OR 1.23, 95%CI 0.62-2.46), vascular complications (OR 0.96, 95%CI 0.70-1.32), acute kidney injury (OR 1.03, 95%CI 0.53-2.00), blood transfusion (OR 0.67, 95% CI 0.45-1.01), major and life-threatening bleed (OR 0.74, 95%CI 0.37-1.49), and BARC bleeding (OR 0.52, 95%CI 0.23-1.18). CONCLUSIONS: In patient undergoing aortic valve interventions, no difference was seen between the use of bivalirudin and heparin as the procedural anticoagulant agent, except for a significant lower myocardial infarction events when bivalirudin was used. Further large randomized trials are needed to confirm current results.

Transcatheter Valve-in-Valve Implantation: Failing Tricuspid Bioprosthesis in a Patient with Ebstein’s Anomaly.

Transcatheter valve-in-valve (VIV) implantation has been recently proposed as an alternative to surgical reoperative aortic valve replacement in patients with a failing aortic bioprosthesis. Experience with transcatheter VIV implantation at other valve positions is very limited. Herein is reported the case of an 18-year-old man with Ebstein's anomaly and severe tricuspid valve (TV) regurgitation status after bioprosthetic valve replacement, who developed new dyspnea on exertion three years after the initial valve replacement. Transesophageal echocardiography showed a severely dilated right atrium and new TV stenosis with an immobile leaflet. The patient underwent successful VIV implantation of a 29-mm SAPIEN XT bioprosthetic valve, with resolution of symptoms and no residual TV regurgitation or stenosis at the two-year follow up. Video 1: Degenerative bioprosthetic tricuspid valve. TEE showing the degenerative bioprosthetic tricuspid valve, and color Doppler during systole showing severe tricuspid regurgitation. Video 2: Degenerative bioprosthetic tricuspid valve. Three-dimensional TEE showing stenosis with an immobile leaflet creating a coaptation defect, viewed from the right atrium. Video 3: Transcatheter VIV replacement with a 29-mm Edwards SAPIEN XT deployed within the tricuspid valve prosthesis. Final result after valve implantation, demonstrating a patent valve orifice, and appropriate apposition of transcatheter valve within a pre-existing surgical Carpentier-Edwards bioprosthetic valve, viewed from the right ventricle. Video 4: Transcatheter VIV replacement with a 29-mm Edwards SAPIEN XT deployed within the tricuspid valve prosthesis. Final result after valve implantation, demonstrating a patent valve orifice, and appropriate apposition of transcatheter valve within a pre-existing surgical Carpentier-Edwards bioprosthetic valve, viewed from the right atrium.

Radiofrequency Ablation in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC).

PURPOSE OF REVIEW: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable form of cardiomyopathy, typically with autosomal dominant transmission, shown to be a defect in the cardiac desmosomes, with distinct regional and histopathological features. Clinically, this can ultimately result in bi-ventricular failure and/or malignant ventricular tachycardia (VT) via reentrant circuits created by patchy scar formation. We sought to review the current treatment for ventricular arrhythmias in the setting of ARVC, with particular attention to radiofrequency (RF) ablation and its varied techniques, along with potential therapies in the ablation spectrum. RECENT FINDINGS: There is underwhelming data on the effectiveness of medical therapy for ARVC-related VT, including beta-blockers and antiarrhythmic medication. Primary and secondary prophylactic implantable-cardioverter defibrillator (ICD) implantation in higher-risk patients is recommended. More recently, RF ablation has been used for ARVC-related VT. Endocardial VT ablation in this setting can produce acute success, though recurrence rate is quite high, which may be explained by the more epicardial and patchy nature of the disease. Combined endocardial-epicardial ablation has since been shown to be feasible, safe, and with significantly better acute and long-term success, particularly when combined with scar dechanneling or homogenization of the scar. However, recurrence rates are not insignificant, and ablation does not eliminate the need for ICD placement. Medical therapy for ARVC-related VT is suboptimal. RF ablation techniques including endocardial and epicardial approaches appear to have the highest success rates for ARVC-related VT. Catheter ablation of VT in ARVC patients should be considered a potentially effective strategy for eliminating frequent VT episodes and ICD shocks rather than a curative therapeutic approach, until long-term efficacy has been consistently documented. Research into the optimal mapping and ablation techniques are promising and ongoing.

Clinical Impact of Heparin Kinetics During Catheter Ablation of Atrial Fibrillation: Meta-Analysis and Meta-Regression.

INTRODUCTION: Appropriate activated clotting time (ACT) during catheter ablation of atrial fibrillation (CA-AF) is essential to minimize periprocedural complications. METHODS AND RESULTS: An electronic search was performed using major databases. Outcomes were thromboembolic (TE) and bleeding complications according to ACT levels (seconds). Heparin dose (U/kg) and time (minutes) to achieve the target ACT was compared among patients receiving vitamin K antagonist (VKA) versus non-VKA oral anticoagulants (NOAC). Nineteen studies involving 7,150 patients were identified. Patients with ACT > 300 had less TE (OR, 0.51; 95% CI 0.35-0.74) and bleeding (OR, 0.70; 95% CI 0.60-0.83) compared to ACT < 300, when using any type of oral anticoagulation. The use of VKA was associated with reduced heparin requirements (mean dose: 157 U/kg vs. 209 U/kg, P < 0.03; SDM -0.86 [95% CI -1.39 to -0.33]), and with lower time to achieve the target ACT (mean time: 24 minutes vs. 49 minutes, P < 0.03; SDM -11.02 [95% CI -13.29 to -8.75]) compared to NOACs. No significant publication bias was found. CONCLUSIONS: Performing CA-AF with a target ACT > 300 decreases the risk of TE without increasing the risk of bleeding. Patients receiving VKAs required less heparin and reached the target ACT faster compared to NOACs.

Speech-induced atrial tachycardia: an unusual presentation of supraventricular tachycardia.

A 63-year-old male radio announcer was admitted with a narrow complex, long RP tachycardia. While in the awake state, the patient spoke in his radio voice, initiating and maintaining the tachycardia. Three-dimensional electroanatomic mapping during electrophysiology study localized the tachycardia to the ostium of the right superior pulmonary vein. After single radiofrequency energy application, no further arrhythmias were inducible with speech. At more than 1 year of follow-up, the patient had no recurrences and continues to work as a radio announcer.

"Silent" dissemination of Klebsiella pneumoniae isolates bearing K. pneumoniae carbapenemase in a long-term care facility for children and young adults in Northeast Ohio.

BACKGROUND: Klebsiella pneumoniae isolates harboring the K. pneumoniae carbapenemase gene (bla(KPC)) are creating a significant healthcare threat in both acute and long-term care facilities (LTCFs). As part of a study conducted in 2004 to determine the risk of stool colonization with extended-spectrum cephalosporin-resistant gram-negative bacteria, 12 isolates of K. pneumoniae that exhibited nonsusceptibility to extended-spectrum cephalosporins were detected. All were gastrointestinal carriage isolates that were not associated with infection. METHODS: Reassessment of the carbapenem minimum inhibitory concentrations using revised 2011 Clinical Laboratory Standards Institute breakpoints uncovered carbapenem resistance. To further investigate, a DNA microarray assay, PCR-sequencing of bla genes, immunoblotting, repetitive-sequence-based PCR (rep-PCR) and multilocus sequence typing (MLST) were performed. RESULTS: The DNA microarray detected bla(KPC) in all 12 isolates, and bla(KPC-3) was identified by PCR amplification and sequencing of the amplicon. In addition, a bla(SHV-11) gene was detected in all isolates. Immunoblotting revealed "low-level" production of the K. pneumoniae carbapenemase, and rep-PCR indicated that all bla(KPC-3)-positive K. pneumoniae strains were genetically related (≥98% similar). According to MLST, all isolates belonged to sequence type 36. This sequence type has not been previously linked with bla(KPC) carriage. Plasmids from 3 representative isolates readily transferred the bla(KPC-3) to Escherichia coli J-53 recipients. CONCLUSIONS: Our findings reveal the "silent" dissemination of bla(KPC-3) as part of Tn4401b on a mobile plasmid in Northeast Ohio nearly a decade ago and establish the first report, to our knowledge, of K. pneumoniae containing bla(KPC-3) in an LTCF caring for neurologically impaired children and young adults.

Intramyocardial mapping of ventricular premature depolarizations via septal venous perforators: Differentiating the superior intraseptal region from left ventricular summit origins.

BACKGROUND: The intramyocardial aspect of the left ventricular summit (LVS) can be mapped by advancing a unipolar guidewire into septal perforator branches of the anterior interventricular vein. OBJECTIVE: The purpose of this study was to differentiate between ventricular premature depolarizations (VPDs) with a basal superior intraseptal (SIS) site of origin and those originating from the epicardial LVS using septal intramyocardial mapping. METHODS: A retrospective cohort of patients with suspected LVS VPDs who underwent SIS unipolar mapping were reviewed for their clinical characteristics, mapping findings, and procedural outcomes. RESULTS: SIS mapping was successful in 44 of 47 cases (93.6%). VPD origin was SIS (defined as earliest activation from the intraseptal wire) in 20 patients (45.5%; median 23 ms pre-QRS). Procedure success was similar in patients with (group 1) and without (group 2) SIS origin (84% vs 87.5%, respectively; P = .842). Of the 10 patients in group 1 without presystolic endocardial activation, 5 (11.3% of all 44 cases) were successfully ablated from the left ventricular endocardium by using an anatomical approach targeting the endocardium closest to the earliest intraseptal activation site. CONCLUSION: A significant proportion (45.5%) of VPDs that appear to arise from the left ventricular summit can be demonstrated to have a SIS origin using septal perforator venous mapping. A significant minority (11.3%) of these can be ablated from the endocardium by targeting from an anatomic vantage point closest to the earliest intraseptal activation site. The described strategy may help differentiate true LVS VPDs from those with SIS sites of origin.

Novel VIM metallo-beta-lactamase variant, VIM-24, from a Klebsiella pneumoniae isolate from Colombia.

We report the emergence of a novel VIM variant (VIM-24) in a Klebsiella pneumoniae isolate in Colombia. The isolate displays MICs for carbapenems below the resistance breakpoints, posing a real challenge for its detection. The blaVIM-24 gene was located within a class 1 integron carried on a large plasmid. Further studies are needed to clarify its epidemiological and clinical impact.

First characterization of CTX-M-15-producing Escherichia coli ST131 and ST405 clones causing community-onset infections in South America.

CTX-M-15-producing Escherichia coli has emerged worldwide as an important pathogen associated with community-onset infections, but in South America reports are scarce. We document the presence of CTX-M-15-producing E. coli of the international ST131 and ST405 clones in Colombia and present the first molecular characterization of these isolates in South America.

First-line ablation of ventricular tachycardia in ischemic cardiomyopathy: stratification of outcomes by left ventricular function.

PURPOSE: First-line catheter ablation of ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with ischemic cardiomyopathy (ICM) has been associated with improved outcomes; however, most benefit seems to be in patients with moderately depressed left ventricular ejection fraction (LVEF). Herein, outcomes were stratified based on LVEF. METHODS: A meta-analysis of randomized controlled trials (RCTs) evaluating first-line ablation versus medical therapy in patients with VT and ICM was performed. Risk estimates and 95% confidence intervals (CI) were measured. RESULTS: Four RCTs with a total of 505 patients (mean age 66 ± 9 years, 89% male, 80% with previous revascularization) were included. Mean LVEF was 35 ± 8%. At a mean follow-up of 24 ± 9 months, a significant benefit in survival-free from appropriate implantable cardioverter-defibrillator (ICD) therapies was observed in all patients undergoing first-line catheter ablation compared with medical management (RR 0.70, 95% CI 0.56-0.86). In patients with moderately depressed LVEF (> 30-50%), first-line VT ablation was associated with a statistically significant reduction in the composite endpoint of survival free from VT/VF and appropriate ICD therapies (HR 0.52, 95% CI 0.36-0.76), whereas there was no difference in patients with severely depressed LVEF (≤30%) (HR 0.56, 95% CI 0.24-1.32). Funnel plots did not show asymmetry suggesting lack of bias. CONCLUSIONS: Patients with ICM and VT undergoing first-line ablation have a significantly lower rate of appropriate ICD therapies without a mortality difference compared with patients receiving an initial approach based on medical therapy. The beneficial effect of a first-line ablation approach was only observed in patients with moderately depressed LVEF (> 30-50%).

Half-Dose Direct Oral Anticoagulation Versus Standard Antithrombotic Therapy After Left Atrial Appendage Occlusion.

OBJECTIVES: This study evaluated the long-term efficacy of a standard antithrombotic strategy versus half-dose direct oral anticoagulation (DOAC) after Watchman implantation. BACKGROUND: No consensus currently exists on the selection of the most effective antithrombotic strategy to prevent device-related thrombosis (DRT) in patients undergoing endocardial left atrial appendage closure. METHODS: After successful left atrial appendage closure, consecutive patients were prescribed a standard antithrombotic strategy (SAT) or long-term half-dose DOAC (hdDOAC). The primary composite endpoint was DRT and thromboembolic (TE) and bleeding events. RESULTS: Overall, 555 patients (mean age 75 ± 8 years, 63% male; median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category] score 4 [interquartile range (IQR): 3-6]; median HAS-BLED [hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol] score 3 [IQR: 2-4]) were included. Patients were categorized into 2 groups (SAT: n = 357 vs hdDOAC: n = 198). Baseline clinical characteristics were similar between groups. The median follow-up duration was 13 months (IQR: 12-15 months). DRT occurred in 12 (2.1%) patients, all in the SAT group (3.4% vs 0.0%; log-rank P = 0.009). The risk of nonprocedural major bleeding was significantly more favorable in the hdDOAC group (0.5% vs. 3.9%; log-rank P = 0.018). The rate of the primary composite endpoint of DRT and TE and major bleeding events was 9.5% in SAT patients and 1.0% in hdDOAC patients (HR: 9.8; 95% CI: 2.3-40.7; P = 0.002). CONCLUSIONS: After successful Watchman implantation, long-term half-dose DOAC significantly reduced the risk of the composite endpoint of DRT and TE and major bleeding events compared with a standard, antiplatelet-based, antithrombotic therapy.