Transcatheter or Surgical Treatment of Aortic-Valve Stenosis.

BACKGROUND: Among low-risk patients with severe, symptomatic aortic stenosis who are eligible for both transcatheter aortic-valve implantation (TAVI) and surgical aortic-valve replacement (SAVR), data are lacking on the appropriate treatment strategy in routine clinical practice. METHODS: In this randomized noninferiority trial conducted at 38 sites in Germany, we assigned patients with severe aortic stenosis who were at low or intermediate surgical risk to undergo either TAVI or SAVR. Percutaneous- and surgical-valve prostheses were selected according to operator discretion. The primary outcome was a composite of death from any cause or fatal or nonfatal stroke at 1 year. RESULTS: A total of 1414 patients underwent randomization (701 to the TAVI group and 713 to the SAVR group). The mean (±SD) age of the patients was 74±4 years; 57% were men, and the median Society of Thoracic Surgeons risk score was 1.8% (low surgical risk). The Kaplan-Meier estimate of the primary outcome at 1 year was 5.4% in the TAVI group and 10.0% in the SAVR group (hazard ratio for death or stroke, 0.53; 95% confidence interval [CI], 0.35 to 0.79; P<0.001 for noninferiority). The incidence of death from any cause was 2.6% in the TAVI group and 6.2% in the SAVR group (hazard ratio, 0.43; 95% CI, 0.24 to 0.73); the incidence of stroke was 2.9% and 4.7%, respectively (hazard ratio, 0.61; 95% CI, 0.35 to 1.06). Procedural complications occurred in 1.5% and 1.0% of patients in the TAVI and SAVR groups, respectively. CONCLUSIONS: Among patients with severe aortic stenosis at low or intermediate surgical risk, TAVI was noninferior to SAVR with respect to death from any cause or stroke at 1 year. (Funded by the German Center for Cardiovascular Research and the German Heart Foundation; DEDICATE-DZHK6 ClinicalTrials.gov number, NCT03112980.).

Timing of Complete Revascularization with Multivessel PCI for Myocardial Infarction.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) with multivessel coronary artery disease, the time at which complete revascularization of nonculprit lesions should be performed remains unknown. METHODS: We performed an international, open-label, randomized, noninferiority trial at 37 sites in Europe. Patients in a hemodynamically stable condition who had STEMI and multivessel coronary artery disease were randomly assigned to undergo immediate multivessel percutaneous coronary intervention (PCI; immediate group) or PCI of the culprit lesion followed by staged multivessel PCI of nonculprit lesions within 19 to 45 days after the index procedure (staged group). The primary end point was a composite of death from any cause, nonfatal myocardial infarction, stroke, unplanned ischemia-driven revascularization, or hospitalization for heart failure at 1 year after randomization. The percentages of patients with a primary or secondary end-point event are provided as Kaplan-Meier estimates at 6 months and at 1 year. RESULTS: We assigned 418 patients to undergo immediate multivessel PCI and 422 to undergo staged multivessel PCI. A primary end-point event occurred in 35 patients (8.5%) in the immediate group as compared with 68 patients (16.3%) in the staged group (risk ratio, 0.52; 95% confidence interval, 0.38 to 0.72; P<0.001 for noninferiority and P<0.001 for superiority). Nonfatal myocardial infarction and unplanned ischemia-driven revascularization occurred in 8 patients (2.0%) and 17 patients (4.1%), respectively, in the immediate group and in 22 patients (5.3%) and 39 patients (9.3%), respectively, in the staged group. The risk of death from any cause, the risk of stroke, and the risk of hospitalization for heart failure appeared to be similar in the two groups. A total of 104 patients in the immediate group and 145 patients in the staged group had a serious adverse event. CONCLUSIONS: Among patients in hemodynamically stable condition with STEMI and multivessel coronary artery disease, immediate multivessel PCI was noninferior to staged multivessel PCI with respect to the risk of death from any cause, nonfatal myocardial infarction, stroke, unplanned ischemia-driven revascularization, or hospitalization for heart failure at 1 year. (Supported by Boston Scientific; MULTISTARS AMI ClinicalTrials.gov number, NCT03135275.).

3D mapping of phrenic nerve course for radiofrequency pulmonary vein isolation.

INTRODUCTION: Phrenic nerve (PN) injury is a rare but severe complication of radiofrequency (RF) pulmonary vein isolation (PVI). The objective of this study was to characterize the typical intracardiac course of the PN with a three-dimensional electroanatomic mapping system, to quantify the need for modification of the ablation trajectory to avoid delivering an ablation lesion on sites with PN capture, and to identify very circumscribed areas of common PNC on the routine ablation trajectory of a RF-PVI, allowing fast and effective PN screening for everyday usage. METHODS: We enrolled 137 consecutive patients (63 ± 9 years, 64% men) undergoing PVI. A detailed high output (20 mA) pace-mapping protocol was performed in the right (RA) and left atrium (LA) and adjacent vasculature. RESULTS: The right PN was most commonly captured in the superior vena cava at a lateral (50%) or posterolateral (23%) position before descending along the RA either straight (29%) or with a posterolateral bend (20%). In the LA, beginning deep within the right superior pulmonary vein (RSPV), the right PN is most frequently detectable anterolateral (31%), then descends to the lateral proximal RSPV (23%), and further towards the lateral antral region (15%) onto the medial LA wall (12%). To avoid delivering an ablation lesion on sites with PN capture, modification of ablation trajectory was necessary in 23% of cases, most commonly in the lateral RSPV antrum (81%). No PN injury occurred. CONCLUSION: PN mapping frequently reveals the close proximity of the PN to the ablation trajectory during PVI, particularly in the lateral RSPV antrum. Routine PN pacing should be considered during RF PVI procedures.

Characterization of circumferential antral pulmonary vein isolation areas resulting from pulsed-field catheter ablation.

AIMS: The cornerstone of pulmonary vein (PV) isolation (PVI) is a wide-area circumferential ablation (WACA) resulting in an antral PVI area. Pulsed-field ablation (PFA) is a new nonthermal 'single-shot' PVI technique resulting in well-characterized posterior isolation areas. However, information on circumferential PVI area is lacking. Thus, we sought to characterize the circumferential antral PVI areas after PFA-PVI. METHODS AND RESULTS: Atrial fibrillation (AF) patients underwent fluoroscopy-guided PVI with a pentaspline PFA catheter. Ultra-high-density voltage maps using a 20-polar circular mapping catheter were created before and immediately after PVI to identify and quantify (i) insufficient isolation areas per antral PV segment (10-segment model) and (ii) enlarged left atrial (LA) isolation areas (beyond the antral PV segments) per LA region (8-region model). The PFA-PVI with pre- (5469 ± 1822 points) and post-mapping (6809 ± 2769 points) was performed in 40 consecutive patients [age 62 ± 6 years, 25/40 (62.5%) paroxysmal AF]. Insufficient isolation areas were located most frequently in the anterior antral PV segments of the left PVs (62.5-77.5% of patients) with the largest extent (median ≥0.4 cm2) located in the same segments (segments 2/5/8). Enlarged LA isolation areas were located most frequently and most extensively on the posterior wall and roof region (89.5-100% of patients; median 1.1-2.7 cm2 per region). CONCLUSION: Fluoroscopy-guided PFA-PVI frequently results in insufficient isolation areas in the left anterior antral PV segments and enlarged LA isolation areas on the posterior wall/roof, which both may be extensive. To optimize the procedure, full integration of PFA catheter visualization into three-dimensional-mapping systems is needed.

Feasibility and safety of a three-dimensional anatomic map-guided transseptal puncture for left-sided catheter ablation procedures.

AIMS: Transseptal puncture (TP) for left-sided catheter ablation procedures is routinely performed under fluoroscopic or echocardiographic guidance [transoesophageal echocardiography (TEE) or intracardiac echocardiography (ICE)], although three-dimensional (3D) mapping systems are readily available in most electrophysiology laboratories. Here, we sought to assess the feasibility and safety of a right atrial (RA) 3D map-guided TP. METHODS AND RESULTS: In 104 patients, 3D RA mapping was performed to identify the fossa ovalis (FO) using the protrusion technique. The radiofrequency transseptal needle was visualized and navigated to the desired potential FO-TP site. Thereafter, the interventionalist was unblinded to TEE and the potential FO-TP site was reassessed regarding its convenience and safety. After TP, the exact TP site was documented using a 17-segment-FO model. Reliable identification of the FO was feasible in 102 patients (98%). In these, 114 3D map-guided TP attempts were performed, of which 96 (84%) patients demonstrated a good position and 18 (16%) an adequate position after TEE unblinding. An out-of-FO or dangerous position did not occur. A successful 3D map-guided TP was performed in 110 attempts (97%). Four attempts (3%) with adequate positions were aborted in order to seek a more convenient TP site. The median time from RA mapping until the end of the TP process was 13 (12-17) min. No TP-related complications occurred. Ninety-eight TP sites (85.1%) were in the central portion or in the inner loop of the FO. CONCLUSION: A 3D map-guided TP is feasible and safe. It may assist to decrease radiation exposure and the need for TEE/ICE during left-sided catheter ablation procedures.

Apixaban vs. standard of care after transcatheter aortic valve implantation: the ATLANTIS trial.

AIMS: The respective roles of oral anticoagulation or antiplatelet therapy following transcatheter aortic valve implantation (TAVI) remain debated. ATLANTIS is an international, randomized, open-label, superiority trial comparing apixaban to the standard of care. METHODS AND RESULTS: After successful TAVI, 1500 patients were randomized (1:1) to receive apixaban 5 mg (2.5 mg if impaired renal function or concomitant antiplatelet therapy) (n = 749) twice daily, or standard of care (n = 751). Randomization was stratified by the need for chronic anticoagulation therapy. Standard-of-care patients received a vitamin K antagonist (VKA) (Stratum 1) or antiplatelet therapy (Stratum 2) if there was an indication for anticoagulation or not, respectively. The primary endpoint was the composite of death, myocardial infarction, stroke or transient ischaemic attack, systemic embolism, intracardiac or bioprosthesis thrombosis, deep vein thrombosis or pulmonary embolism, and life-threatening, disabling, or major bleeding over 1-year follow-up. The primary safety endpoint was major, disabling, or life-threatening bleeding. The primary outcome occurred in 138 (18.4%) and 151 (20.1%) patients receiving apixaban or standard of care, respectively [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.73-1.16] and there was no evidence of interaction between treatment and stratum (Pinteraction = 0.57). The primary safety endpoint was similar in both groups (HR 1.02; 95% CI 0.72-1.44). In Stratum 1 (n = 451), an exploratory analysis showed no difference for all endpoints between apixaban and VKA. In Stratum 2 (n = 1049), the primary outcome and primary safety endpoint did not differ, but obstructive valve thrombosis was reduced with apixaban vs. antiplatelet therapy (HR 0.19; 95% CI 0.08-0.46), while a signal of higher non-cardiovascular mortality was observed with apixaban. CONCLUSION: After TAVI, apixaban was not superior to the standard of care, irrespective of an indication for oral anticoagulation.

Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes.

BACKGROUND: The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain. METHODS: In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding. RESULTS: A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46). CONCLUSIONS: Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).

5-Year outcomes after transcatheter aortic valve implantation: Focus on paravalvular leakage assessed by echocardiography and hemodynamic parameters.

OBJECTIVES: We sought to assess the impact of echocardiographic and hemodynamic grading of paravalvular leakage (PVL) after transcatheter aortic valve implantation (TAVI) on the prediction of 5-year mortality. PVL after TAVI is known to influence outcome after TAVI. Yet, present available data of long-term outcomes and especially the comparison of different modalities for measurement of PVL is little. METHODS: We performed a retrospective single-center cohort study and compared the prognostic value of echocardiographic PVL grading as well as the aortic regurgitation index (ARI) pre- and post-TAVI. Univariable and multivariable Cox proportional regression analysis generated hazard ratios for mortality. RESULTS: A total of 464 patients underwent TAVI at our center between August 2012 and Decemebr 2014, with self-expandable CoreValve (11%) or balloon-expandable Sapien XT (47.4%) and Sapien 3 (41.6) valves. Overall 5-year mortality was 52.4% (243/464). Echocardiographic classes of PVL at discharge showed a significant (p = 0.002) association with 5-year mortality, mild PVL remained as an independent predictor for 5-year mortality in multivariable analysis (hazard ratio: 1.642 [95% confidence interval: 1.235-2.182]; p = 0.001). Grades of PVL as assessed during the procedure by ARI (below the previously defined cut-off of 25) did not show a significant association with 5-year mortality (p = 0.417 and p = 0.995, respectively). CONCLUSIONS: Even mild PVL assessed by echocardiography was an independent predictor for 5-year survival, whereas hemodynamic measurements did not help to identify PVLs that are relevant to 5-year survival.

Mortality Following Treatment With and Without Paclitaxel-Coated Devices in Dialysis Patients.

OBJECTIVES: To evaluate the mortality after treatment with a paclitaxel (PTX)-coated device and with uncoated devices of iliac, femoropopliteal, and below-the-knee lesions in dialysis patients. METHODS: Retrospective mortality analysis of dialysis patients with peripheral artery disease who underwent treatment of iliac, femoropopliteal, and/or infrapopliteal lesions with PTX-coated or uncoated devices. RESULTS: Between 2010 and 2018, 1125 dialysis patients were treated with iliac and/or femoropopliteal and/or infrapopliteal lesions. In all, 359 patients were selected for this retrospective analysis. Of those, 122 patients were treated with uncoated devices without crossover to a PTX-coated device during follow-up and 237 patients were treated with a PTX-coated device. Mean follow-up time was 27.38±24.76 months (range=0-103). For the entire cohort, the overall mortality was 95.1% after uncoated treatment and 75.9% after PTX treatment (p<0.001). After propensity score matching (n=119), overall mortality was 95.0% after uncoated treatment and 78.2% after PTX treatment (p<0.001). For the entire cohort, multivariate logistic regression analysis revealed age (p=0.002) and critical limb ischemia (p<0.001) as independent predictors for mortality. PTX treatment was a protective factor for mortality (p<0.001). CONCLUSION: Mortality in dialysis patients is in general high and higher after use of uncoated devices compared with PTX-coated devices. Mortality predictors were risk factors and disease severity but not PTX treatment. CLINICAL IMPACT: After the publication of Katsanos's metaanalyses, the uncertainty regarding PTX device safety in peripheral interventions in patients mainly without end-stage renal insufficiency was initially considerable. The present study for the first time investigates the potential long-term mortality risk of dialysis patients following PTX device treatment of PAD. In contrast to a recent meta-analysis, this real-world study could show a better survival after PTX treatment in comparison to uncoated devices.

Comparison of various late gadolinium enhancement magnetic resonance imaging methods with high-definition voltage and activation mapping for detection of atrial cardiomyopathy.

AIMS: Atrial cardiomyopathy (ACM) is associated with increased arrhythmia recurrence rates after pulmonary vein isolation (PVI). We compare the most common left atrial (LA) late gadolinium enhancement magnetic resonance imaging (LGE-MRI)-methods [Utah-method and image intensity ratio (IIR)-methods] and endocardial voltage mapping for ACM-detection and outcome prediction after PVI for atrial fibrillation (AF). METHODS AND RESULTS: In this prospective observational study, 37 ablation-naive patients (66 ± 9 years, 84% male) with persistent AF underwent LA-LGE-MRI and high-definition voltage and activation mapping (2129 ± 484 sites) in sinus rhythm prior to PVI. The MRI-post-processing-analyses were performed by two independent expert laboratories. Arrhythmia recurrence was recorded within 12 months following PVI. The global ACM-extent was highly variable: median LA low-voltage substrate (LA-LVS) was 12.9% at <1.0 mV and 2.7% at <0.5 mV; median LA-LGE-extent using the Utah-method was 18.3% and 0.03-93.1% using the IIR-methods. The LA activation time was significantly correlated with LA-LVS (r = 0.76 at <0.5 mV and r = 0.82 at <1.0 mV, both P < 0.0001), but not with LA-LGE-extent. The highest regional matching between LA-LVS <0.5 mV and LA-LGE was found for the anterior wall in 57% of patients using the Utah-method and in 59% using IIR 1.20. The corresponding values for the posterior wall were 19% and 38%, respectively. Arrhythmia recurrence occurred in 15(41%) patients. Freedom from arrhythmia was significantly lower in those with LA-LVS ≥2 cm2 at 0.5 mV but not in those with LGE ≥20% (Utah-stages III and IV): 43% vs. 81%, P = 0.009 and 50% vs. 67%, P = 0.338, respectively. CONCLUSION: Comparison of the most common LA-LGE-MRI methods and endocardial voltage mapping revealed large discrepancies in global and regional ACM-extent.

Association of lipoprotein(a) with intrinsic and on-clopidogrel platelet reactivity.

Lipoprotein(a) [Lp(a)] is an independent, genetically determined, and causal risk factor for cardiovascular disease. Laboratory data have suggested an interaction of Lp(a) with platelet function, potentially caused by its interaction with platelet receptors. So far, the potential association of Lp(a) with platelet activation and reactivity has not been proven in larger clinical cohorts. This study analyzed intrinsic platelet reactivity before loading with clopidogrel 600 mg and on-treatment platelet reactivity tested 24 h following loading in patients undergoing elective coronary angiography. Platelet reactivity was tested by optical aggregometry following stimulation with collagen or adenosine diphosphate as well as by flow cytometry. Lp(a) levels were directly measured in all patients from fresh samples. The present analysis included 1912 patients. Lp(a) levels ranged between 0 and 332 mg/dl. There was a significant association of rising levels of Lp(a) with a higher prevalence of a history of ischemic heart disease (p < 0.001) and more extensive coronary artery disease (p = 0.001). Results for intrinsic (p = 0.80) and on-clopidogrel platelet reactivity (p = 0.81) did not differ between quartiles of Lp(a) levels. Flow cytometry analyses of expression of different platelet surface proteins (CD41, CD62P or PAC-1) confirmed these findings. Correlation analyses of levels of Lp(a) with any of the tested platelet activation markers did not show any correlation. The present data do not support the hypothesis of an interaction of Lp(a) with platelet reactivity.

Invasive Coronary Angiography in Patients with Native or Prosthetic Aortic Valve Endocarditis.

BACKGROUND: Invasive coronary angiography (ICA) is essential to detect significant coronary artery disease (CAD) but is generally not recommended in patients with infective aortic valve endocarditis. This study aimed to evaluate the risks and benefits of preoperative ICA in patients before aortic valve replacement. METHODS: Between March 2008 and September 2020, 232 patients were surgically treated for infectious endocarditis of the aortic valve. Sixty-seven (29%) of them underwent preoperative diagnostic ICA and were compared with the patients without preoperative ICA. We collected their baseline characteristics, including the neurological status, previous cardiac surgical procedures, and reviewed the preoperative echocardiograms and the ICA data. The intraoperative data and clinical outcomes after ICA and after surgery were evaluated. RESULTS: ICA revealed a CAD in the majority of our patients (n = 36; 54%): One-vessel disease n = 19 (28%), two-vessel disease n = 6 (9%), and three-vessel disease n = 11 (16%). We observed no adverse events following preoperative diagnostic ICA, particularly no thromboembolic complications, including stroke, visceral, or lower body ischemia were detected. During surgical aortic valve replacement, concomitant coronary artery bypass grafting was performed in 20 patients (30%). In patients with preoperative ICA, postoperative in-hospital mortality was significantly lower (n = 8 [12%] vs. n = 30 [18%]; p < 0.001), while the incidence of postoperative bleeding was higher (n = 18 [27%] vs. n = 22 [13%]; p = 0.022). The new-onset stroke incidence was 5% in each group. CONCLUSION: Taking a multidisciplinary team approach, ICA is safe in selected patients with aortic valve infectious endocarditis with no adverse clinical outcomes, but significant clinical implications.

Diabetes, heart failure, and myocardial revascularization: Is there a new message from the ISCHEMIA trial?

There is no evidence that the indications for myocardial revascularization differ between patients with and without diabetes. Accepted indications include stable angina that cannot be adequately managed by medication, acute coronary syndromes, severely reduced left ventricular (LV) function due to coronary artery disease, left main stenosis, and advanced coronary artery disease causing substantial inducible ischemia. The recent ISCHEMIA trial challenged the criterion of ischemia. With respect to its primary endpoint, ISCHEMIA showed no benefit of an invasive strategy with systematic myocardial revascularization in patients with stable angina and moderate-to-severe ischemia compared with a conservative strategy. However, myocardial revascularization resulted in a statistically significant and clinically meaningful reduction in angina and an improvement in quality of life. There was a significant reduction in prognostically relevant spontaneous myocardial infarction (MI) in the long term, which came at the cost of an increased rate of peri-interventional MI that was of minor prognostic relevance. The risk profile and number of patients included in the ISCHEMIA trial, as well as the duration of follow-up, are not sufficient to show that the lower incidence of spontaneous infarcts improved survival. In ISCHEMIA, there was no heterogeneity in treatment effect depending on diabetes.

Subsequent cardiac surgery after transcatheter aortic valve implantation: Indications and outcomes.

BACKGROUND: Aim of this study was to report on indications and clinical outcomes of patients who underwent subsequent open-cardiac surgery after transcatheter aortic valve implantation TAVI. METHODS: Between 01/2011 and 12/2020 our centre performed 4043 TAVI procedures. Twenty-seven patients (including patients in whom TAVI was performed in other centres) underwent subsequent open-heart surgery via cardiopulmonary bypass. Demographic, intraprocedural data, indications for, and outcomes after surgery were evaluated. RESULTS: Indications for cardiac surgery (aged 79 [IQR 76-84]; 59.3% male) were endocarditis (n = 11; 40.7%), annular rupture, severe paravalvular leak and severe stenosis in three (11.1%) patients, respectively as well as in one patient each (3.7%) severe tricuspid valve regurgitation, valve thrombosis, valve malposition, valve migration, ostial right coronary artery obstruction, left ventricular rupture and type A aortic dissection. The interval between the index TAVI procedure to open surgery was 3 months (IQR 0-26 months). Eight patients underwent emergent surgical conversions. Immediate procedural and procedural mortality was 25.9% and 40.7%, respectively and all-cause mortality was 51.9% (11/12 died for cardiovascular reasons). No disabling stroke was observed postoperatively. New permanent pacemaker implantation was required in three patients (11.1%). CONCLUSIONS: Subsequent open-cardiac surgery after TAVI is rare, but may urgently become necessary due to TAVI related complications or progressing other cardiac pathologies. Despite a substantial early attrition rate clinical outcome is acceptable and a relevant number of these high-risk patients can be discharged even after emergency conversions. The option of subsequent surgical conversion remains.

Long-Term Safety and Efficacy of Durable Polymer Cobalt-Chromium Everolimus-Eluting Stents in Patients at High Bleeding Risk: A Patient-Level Stratified Analysis From Four Postapproval Studies.

BACKGROUND: Long-term outcomes in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention with a drug-eluting stent are unclear. Therefore, we aimed to evaluate long-term adverse events in HBR patients undergoing percutaneous coronary intervention with cobalt-chromium everolimus-eluting stent implantation. METHODS: We analyzed stratified data from 4 all-comers postapproval registries. Patients with at least 1 of the following criteria were categorized as HBR: age ≥75 years, history of major bleeding (MB), history of stroke, chronic oral anticoagulant use, chronic kidney disease, anemia, or thrombocytopenia. Additionally, in a separate analysis, patients were categorized according to the recently published Academic Research Consortium HBR criteria. The Kaplan-Meier method was used for time-to-event analyses. Coronary thrombotic events (CTE) included myocardial infarction or definite/probable stent thrombosis. MB was defined according to the TIMI (Thrombolysis in Myocardial Infarction) or GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) scales. Impact of CTE and MB on subsequent risk of mortality was assessed using multivariable Cox regression with MB and CTE included as time-updated covariates. RESULTS: Of the total 10 502 patients included, 3507 (33%) were identified as HBR. Compared with non-HBR patients, those at HBR had more comorbidities, higher lesion complexity, and a higher risk of 4-year mortality (Hazard Ratio [HR] 4.38 [95% CI, 3.76-5.11]). Results were qualitatively similar when using Academic Research Consortium criteria to define HBR. Risk of mortality was increased after CTE (HR 5.02 [95% CI, 3.93-6.41]), as well as after MB (HR 4.92 [95% CI, 3.82-6.35]). Of note, this effect was consistent across the spectrum of bleeding risk (P-interaction test 0.97 and 0.06, respectively). CONCLUSIONS: Compared with the non-HBR population, HBR patients experienced worse 4-year outcomes after percutaneous coronary intervention with cobalt-chromium everolimus-eluting stent. Both CTE and MB had a significant impact on subsequent risk of mortality irrespective of bleeding risk.

Ticagrelor or Prasugrel in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND: Data on the comparative efficacy and safety of ticagrelor versus prasugrel in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention are limited. We assessed the efficacy and safety of ticagrelor versus prasugrel in a head-to-head comparison in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. METHODS: In this prespecified subgroup analysis, we included 1653 patients with ST-segment-elevation myocardial infarction randomized to receive ticagrelor or prasugrel in the setting of the ISAR REACT-5 trial (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5). The primary end point was the incidence of death, myocardial infarction, or stroke at 1 year after randomization. The secondary end point was the incidence of bleeding defined as BARC (Bleeding Academic Research Consortium) type 3 to 5 bleeding at 1 year after randomization. RESULTS: The primary end point occurred in 83 patients (10.1%) in the ticagrelor group and in 64 patients (7.9%) in the prasugrel group (hazard ratio, 1.31 [95% CI, 0.95-1.82]; P=0.10). One-year incidence of all-cause death (4.9% versus 4.7%; P=0.83), stroke (1.3% versus 1.0%; P=0.46), and definite stent thrombosis (1.8% versus 1.0%; P=0.15) did not differ significantly in patients assigned to ticagrelor or prasugrel. One-year incidence of myocardial infarction (5.3% versus 2.8%; hazard ratio, 1.95 [95% CI, 1.18-3.23]; P=0.010) was higher with ticagrelor than with prasugrel. BARC type 3 to 5 bleeding occurred in 46 patients (6.1%) in the ticagrelor group and in 39 patients (5.1%) in the prasugrel group (hazard ratio, 1.22 [95% CI, 0.80-1.87]; P=0.36). CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, there was no significant difference in the primary end point between prasugrel and ticagrelor. Ticagrelor was associated with a significant increase in the risk for recurrent myocardial infarction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01944800.

Rationale and design of a randomized clinical trial comparing safety and efficacy of myval transcatheter heart valve versus contemporary transcatheter heart valves in patients with severe symptomatic aortic valve stenosis: The LANDMARK trial.

BACKGROUND: The recent approval of transcatheter aortic valve replacement (TAVR) in patients with low operative risk has paved the way for the introduction of novel and potentially improved technologies. The safety and efficacy of these novel technologies should be investigated in randomized control trials against the contemporary TAVR devices. The objective of the LANDMARK trial is to compare the balloon-expandable Myval transcatheter heart valve (THV) series with contemporary THV (SAPIEN THV and Evolut THV series) series in patients with severe symptomatic native aortic stenosis. METHODS/DESIGN: The LANDMARK trial (ClinicalTrials.govNCT04275726, EudraCT number 2020-000,137-40) is a prospective, randomized, multinational, multicenter, open-label, and noninferiority trial of approximately 768 patients treated with TAVR via the transfemoral approach. Patients will be allocated in a 1:1 randomization to Myval THV series (n = 384) or to contemporary THV (n = 384) (either of SAPIEN THV or Evolut THV series). The primary combined safety and efficacy endpoint is a composite of all-cause mortality, all stroke (disabling and nondisabling), bleeding (life-threatening or disabling), acute kidney injury (stage 2 or 3), major vascular complications, prosthetic valve regurgitation (moderate or severe), and conduction system disturbances (requiring new permanent pacemaker implantation), according to the Valve Academic Research Consortium-2 criteria at 30-day follow-up. All patients will have follow-up to 10 years following TAVR. SUMMARY: The LANDMARK trial is the first randomized head-to-head trial comparing Myval THV series to commercially available THVs in patients indicated for TAVR. We review prior data on head-to-head comparisons of TAVR devices and describe the rationale and design of the LANDMARK trial.

Design and rationale of the XIENCE short DAPT clinical program: An assessment of the safety of 3-month and 1-month DAPT in patients at high bleeding risk undergoing PCI with an everolimus-eluting stent.

Dual antiplatelet therapy (DAPT) is key for the prevention of recurrent ischemic events after percutaneous coronary intervention (PCI); however, it increases the risk of bleeding complications. While new generation drug-eluting stents have been shown superior to bare-metal stents after a short DAPT course, the optimal DAPT duration in patients at high bleeding risk (HBR) remains to be determined. TRIAL DESIGN: The XIENCE Short DAPT program consists of three prospective, single-arm studies (XIENCE 90, XIENCE 28 Global and XIENCE 28 USA) investigating 3- or 1-month DAPT durations in HBR patients undergoing PCI with the XIENCE stent. The XIENCE 90 study is being conducted in the US and enrolled 2047 subjects who discontinued DAPT at 3 months if they were free from myocardial infarction (MI), repeat coronary revascularization, stroke, or stent thrombosis. The XIENCE 28 program includes the USA study, enrolling 642 patients in US and Canada, and the Global study, enrolling 963 patients in Europe and Asia. In XIENCE 28, patients were to discontinue DAPT at 1 month post-PCI if event-free. The primary hypothesis for both XIENCE 90 and XIENCE 28 is that a short DAPT regimen will be non-inferior to a conventional DAPT duration with respect to the composite of all-cause death or MI. Patients enrolled in the prospective multicenter post-market XIENCE V USA study will be used as historical control group in a stratified propensity-adjusted analysis. CONCLUSIONS: The XIENCE Short DAPT Program will provide insights into the safety and efficacy of 2 abbreviated DAPT regimens of 3- and 1-month duration in a large cohort of HBR patients undergoing PCI with the XIENCE stent.

Eosinophil-platelet interactions promote atherosclerosis and stabilize thrombosis with eosinophil extracellular traps.

Clinical observations implicate a role of eosinophils in cardiovascular diseases because markers of eosinophil activation are elevated in atherosclerosis and thrombosis. However, their contribution to atherosclerotic plaque formation and arterial thrombosis remains unclear. In these settings, we investigated how eosinophils are recruited and activated through an interplay with platelets. Here, we provide evidence for a central importance of eosinophil-platelet interactions in atherosclerosis and thrombosis. We show that eosinophils support atherosclerotic plaque formation involving enhanced von Willebrand factor exposure on endothelial cells and augmented platelet adhesion. During arterial thrombosis, eosinophils are quickly recruited in an integrin-dependent manner and engage in interactions with platelets leading to eosinophil activation as we show by intravital calcium imaging. These direct interactions induce the formation of eosinophil extracellular traps (EETs), which are present in human thrombi and constitute a substantial part of extracellular traps in murine thrombi. EETs are decorated with the granule protein major basic protein, which causes platelet activation by eosinophils. Consequently, targeting of EETs diminished thrombus formation in vivo, which identifies this approach as a novel antithrombotic concept. Finally, in our clinical analysis of coronary artery thrombi, we identified female patients with stent thrombosis as the population that might derive the greatest benefit from an eosinophil-inhibiting strategy. In summary, eosinophils contribute to atherosclerotic plaque formation and thrombosis through an interplay with platelets, resulting in mutual activation. Therefore, eosinophils are a promising new target in the prevention and therapy of atherosclerosis and thrombosis.

Prognostic value of haemoglobin drop in patients with acute coronary syndromes.

BACKGROUND: The prognostic value of in-hospital haemoglobin drop in patients with acute coronary syndrome (ACS) undergoing invasive therapy remains insufficiently investigated. MATERIALS AND METHODS: This observational study included 3838 patients with ACS with admission and in-hospital nadir haemoglobin values available. Haemoglobin drop was defined as a positive difference between admission and nadir haemoglobin values. The primary endpoint was one-year all-cause mortality. RESULTS: In-hospital haemoglobin drop occurred in 3142 patients (82%). Patients were categorized into 4 groups: no haemoglobin drop (n = 696 patients), <3 g/dl haemoglobin drop (n = 2703 patients), 3 to <5 g/dl haemoglobin drop (n = 344 patients) and ≥5 g/dl haemoglobin drop (n = 95 patients). The primary endpoint occurred in 156 patients: 17 patients (2.5%) in the group with no haemoglobin drop, 81 patients (3.0%) in the group with <3g/dl haemoglobin drop, 37 patients (10.9%) in the group with 3 to <5 g/dl haemoglobin drop and 21 patients (22.2%) in the group with ≥5 g/dl haemoglobin (adjusted hazard ratio [HR] = 1.30, 95% confidence interval 1.17 to 1.45; p < .001 for one g/dl haemoglobin drop). The association of haemoglobin drop with one-year mortality remained significant after exclusion of patients with in-hospital overt bleeding (adjusted HR = 1.27 [1.11-1.46]; p < .001 for one g/dl haemoglobin drop). The lowest haemoglobin drop associated with mortality was 1.23 g/dl in all patients (HR = 1.03 [1.02-1.04]) and 1.13 g/dl in patients without overt bleeding (HR = 1.03 [1.01-1.04]). CONCLUSIONS: In patients with ACS, in-hospital haemoglobin drop was associated with higher risk of one-year mortality even in the absence of overt bleeding.