TransCatheter aortic valve implantation and fractional flow reserve-guided percutaneous coronary intervention versus conventional surgical aortic valve replacement and coronary bypass grafting for treatment of patients with aortic valve stenosis and multivessel or advanced coronary disease: The transcatheter valve and vessels trial (TCW trial): Design and rationale.

BACKGROUND: Patients with severe aortic stenosis (AS) frequently present with concomitant obstructive coronary artery disease (CAD). In those, current guidelines recommend combined coronary artery bypass grafting (CABG) and surgical aortic valve replacement (SAVR) as the preferred treatment option, although this surgical approach is associated with a high rate of clinical events. Combined transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) with or without FFR have evolved as a valid alternative for cardiac surgery in patients with AS and multivessel or advanced CAD. To date, no dedicated trial has prospectively evaluated the outcomes of a percutaneous versus surgical treatment for patients with both severe AS and CAD. AIMS: To investigate whether fractional-flow reserve (FFR)-guided PCI and TAVI is noninferior to combined CABG and SAVR for the treatment of severe AS and multivessel or advanced CAD. METHODS: The Transcatheter Valve and Vessels (TCW) trial (clinicaltrial.gov: NCT03424941) is a prospective, randomized, controlled, open label, international trial. Patients ≥ 70 years with severe AS and multivessel (≥ 2 vessels) or advanced CAD, deemed feasible by the heart team for both; a full percutaneous or surgical treatment, will be randomised in a 1:1 fashion to either FFR-guided PCI followed by TAVI (intervention arm) vs. CABG and SAVR (control arm). The primary endpoint is a patient-oriented composite of all-cause mortality, myocardial infarction, disabling stroke, unscheduled clinically-driven target vessel revascularization, valve reintervention, and life threatening or disabling bleeding at 1 year. The TCW trial is powered for noninferiority, and if met, superiority will be tested. Assuming a primary endpoint rate of 30% in the CABG-SAVR arm, with a significance level α of 5%, a noninferiority limit delta of 15% and a loss to follow-up of 2%, a total of 328 patients are needed to obtain a power of 90%. The primary endpoint analysis is performed on an intention-to-treat basis. SUMMARY: The TCW Trial is the first prospective randomized trial that will study if a less invasive percutaneous treatment for severe AS and concomitant advanced CAD (i.e., FFR-guided PCI-TAVI) is noninferior to the guidelines recommended approach (CABG-SAVR).

Resumption of Antiplatelet Therapy after Major Bleeding.

Major bleeding is a common threat in patients requiring antiplatelet therapy. Timing and intensity with regard to resumption of antiplatelet therapy represent a major challenge in clinical practice. Knowledge of the patient's bleeding risk, defining transient/treatable and permanent/untreatable risk factors for bleeding, and weighing these against thrombotic risk are key to successful prevention of major adverse events. Shared decision-making involving various disciplines is essential to determine the optimal strategy. The present article addresses clinically relevant questions focusing on the most life-threatening or frequently occurring bleeding events, such as intracranial hemorrhage and gastrointestinal bleeding, and discusses the evidence for antiplatelet therapy resumption using individual risk assessment in high-risk cardiovascular disease patients.

Outcomes of Patients With Hypertrophic Obstructive Cardiomyopathy and Pacemaker Implanted After Alcohol Septal Ablation.

BACKGROUND: Atrioventricular block is a frequent major complication after alcohol septal ablation (ASA). OBJECTIVES: The aim of this study was to evaluate the outcomes of patients with implanted permanent pacemaker (PPM) related to a high-grade atrioventricular block after ASA for hypertrophic obstructive cardiomyopathy. METHODS: We used a multinational registry (the Euro-ASA registry) to evaluate the outcome of patients with PPM after ASA. RESULTS: A total of 1,814 patients were enrolled and followed up for 5.0 ± 4.3 years (median = 4.0 years). A total of 170 (9.4%) patients underwent PPM implantation during the first 30 days after ASA. Using propensity score matching, 139 pairs (n = 278) constituted the matched PPM and non-PPM groups. Between the matched groups, there were no long-term differences in New York Heart Association functional class (1.5 ± 0.7 vs 1.5 ± 0.9, P = 0.99) and survival (log-rank P = 0.47). Patients in the matched PPM group had lower long-term left ventricular (LV) outflow gradient (12 ± 12 mm Hg vs 17 ± 19 mm Hg, P < 0.01), more pronounced LV outflow gradient decrease (81% ± 17% vs 72% ± 35%, P < 0.01), and lower LV ejection fraction (64% ± 8% vs 66% ± 8%, P = 0.02) and were less likely to undergo reintervention (re-ASA or myectomy) (log-rank P = 0.02). CONCLUSIONS: Patients with hypertrophic obstructive cardiomyopathy treated with ASA have a 9% probability of PPM implantation within 30 days after ASA. In long-term follow-up, patients with PPM had similar long-term survival and New York Heart Association functional class but lower LV outflow gradient, a more pronounced LV outflow gradient decrease, a lower LV ejection fraction, and a lower likelihood of reintervention compared with patients without PPM.

Impact of SARS-CoV-2 positivity on clinical outcome among STEMI patients undergoing mechanical reperfusion: Insights from the ISACS STEMI COVID 19 registry.

BACKGROUND AND AIMS: SARS-Cov-2 predisposes patients to thrombotic complications, due to excessive inflammation, endothelial dysfunction, platelet activation, and coagulation/fibrinolysis disturbances. The aim of the present study was to evaluate clinical characteristics and prognostic impact of SARS-CoV-2 positivity among STEMI patients undergoing primary percutaneous coronary intervention (PPCI). METHODS: We selected SARS-CoV-2 positive patients included in the ISACS-STEMI COVID-19, a retrospective multicenter European registry including 6609 STEMI patients treated with PPCI from March 1st until April 30th, in 2019 and 2020. As a reference group, we randomly sampled 5 SARS-Cov-2 negative patients per each SARS-CoV-2 positive patient, individually matched for age, sex, and hospital/geographic area. Study endpoints were in-hospital mortality, definite stent thrombosis, heart failure. RESULTS: Our population is represented by 62 positive SARS-CoV-2 positive patients who were compared with a matched population of 310 STEMI patients. No significant difference was observed in baseline characteristics or the modality of access to the PCI center. In the SARS-CoV-2 positive patients, the culprit lesion was more often located in the RCA (p < 0.001). Despite similar pre and postprocedural TIMI flow, we observed a trend in higher use of GP IIb-IIIa inhibitors and a significantly higher use of thrombectomy in the SARS-CoV-2 positive patients. SARS-CoV-2 positivity was associated with a remarkably higher in hospital mortality (29% vs 5.5%, p < 0.001), definite in-stent thrombosis (8.1% vs 1.6%, p = 0.004) and heart failure (22.6% vs 10.6%, p = 0.001) that was confirmed after adjustment for confounding factors. CONCLUSIONS: Our study showed that among STEMI patients, SARS-CoV-2 positivity is associated with larger thrombus burden, a remarkably higher mortality but also higher rates of in-stent thrombosis and heart failure.

Impact of COVID-19 Pandemic on Mechanical Reperfusion for Patients With STEMI.

BACKGROUND: The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality. OBJECTIVES: The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of "at-risk" patient cohorts for failure to present or delays to treatment. METHODS: This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020. Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality. RESULTS: A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p < 0.0001). The heterogeneity among centers was not related to the incidence of death due to COVID-19. A significant interaction was observed for patients with arterial hypertension, who were less frequently admitted in 2020 than in 2019. Furthermore, the pandemic was associated with a significant increase in door-to-balloon and total ischemia times, which may have contributed to the higher mortality during the pandemic. CONCLUSIONS: The COVID-19 pandemic had significant impact on the treatment of patients with STEMI, with a 19% reduction in PPCI procedures, especially among patients suffering from hypertension, and a longer delay to treatment, which may have contributed to the increased mortality during the pandemic. (Primary Angioplasty for STEMI During COVID-19 Pandemic [ISACS-STEMI COVID-19] Registry; NCT04412655).

Effect of impaired cardiac conduction after alcohol septal ablation on clinical outcomes: insights from the Euro-ASA registry.

AIMS: We analysed the impact of bundle branch block (BBB) and pacemaker (PM) implantation on symptoms and survival after alcohol septal ablation (ASA) in patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Among 1416 HCM patients from the Euro-ASA registry, 58 (4%) patients had a PM and 64 (5%) patients had an implantable cardioverter-defibrillator (ICD) before ASA. At latest follow-up (5.0 ± 4.0 years) after ASA, 118 (8%) patients had an ICD and 229 (16%) patients had a PM. In patients without an implantable device prior to ASA 13% had a PM and 5% had an ICD implanted following ASA. New onset BBB was present in 44% (right BBB in 31%) of patients without previous BBB. At latest follow-up, we found no associations between BBB and New York Heart Association (NYHA) Class 3-4 [odds ratio (OR) 0.98, 95% confidence interval (CI) 0.63-1.51; P = 0.91] or Canadian Cardiovascular Society (CCS) Class 3-4 (OR 1.5, CI 0.32-6.7; P = 0.62), respectively, and no associations between PM and NYHA Class 3-4 (OR 1.2, CI 0.70-2.0; P = 0.52) or CCS 3-4 (OR 1.3, CI 0.24-6.6; P = 0.79), respectively. The survival after ASA was not reduced in patients with BBB [hazard ratio (HR) 0.73, CI 0.53-1.01; P = 0.06] or PM (HR 0.78, CI 0.52-1.17; P = 0.24). CONCLUSIONS: Development of BBB or need for a PM after ASA in patients with obstructive HCM was not associated with inferior symptomatic outcome or reduced survival, thus concerns for the negative impact of impaired cardiac conduction on the clinical outcome after ASA were not confirmed.

Design and rationale of the WOEST trial: What is the Optimal antiplatElet and anticoagulant therapy in patients with oral anticoagulation and coronary StenTing (WOEST).

BACKGROUND: Long-term oral anticoagulant treatment is obligatory in patients (class I) with mechanical heart valves and most patients with atrial fibrillation. When these patients undergo percutaneous coronary intervention with stenting, there is also an indication for treatment with aspirin and clopidogrel. However, triple therapy is known to increase the risk of bleeding complications. Unfortunately, there are no prospective data available to resolve this issue. Nevertheless, it all comes down to finding the ideal therapy in patients with indications of both chronic anticoagulation therapy and percutaneous intervention to prevent thrombotic complications (eg, stent thrombosis) without increasing the risk of bleeding. OBJECTIVES: This prospective randomized multicenter study will assess the hypothesis that after percutaneous coronary intervention with stent implantation in patients on oral anticoagulant therapy, the combination of oral anticoagulation therapy and clopidogrel 75 mg/d reduces the risk of bleeding and is not inferior to triple therapy treatment with respect to the prevention of thrombotic complications. DESIGN: Multicenter, international, open-label randomized trial evaluating triple therapy (clopidogrel + oral anticoagulants + aspirin) in patients with an indication for oral anticoagulants who undergo coronary stenting versus the combination of oral anticoagulants and clopidogrel. The primary outcome is the combination of TIMI and GUSTO minor and major bleeding up to 30 days and 1 year. The secondary outcomes are major adverse cardiac events. The sample size is 496. CONCLUSIONS: No prospective randomized study has yet addressed the issue of optimal antiplatelet therapy in patients with chronic oral anticoagulant therapy undergoing coronary stenting. Therefore, the WOEST trial will help to define new guidelines for patients with indication for chronic anticoagulation who need coronary stenting.