Prediction of Coronary Risk by SYNTAX and Derived Scores Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery

The introduction of the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score has prompted a renewed interest for angiographic risk stratification in patients undergoing percutaneous coronary intervention. Syntax score is based on qualitative and quantitative characterization of coronary artery disease by including 11 angiographic variables that take into consideration lesion location and characteristics. Thus far, this score has been shown to be an effective tool to risk-stratify patients with complex coronary artery disease undergoing percutaneous coronary intervention in the landmark SYNTAX trial, as well as in other clinical settings. This review provides an overview of its current applications, including its integration with other nonangiographic clinical scores, and explores future applications of the SYNTAX and derived scores. (C) 2013 by the American College of Cardiology FoundationAbbott VascularDoris Duke Charitable FoundationColumbia Univ, Med Ctr, New York, NY 10022 USACardiovasc Res Fdn, New York, NY USAUniv Bologna, Ist Cardiol, Bologna, ItalyUniversidade Federal de São Paulo, Hosp Israelita Albert Einstein, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilUniv Montreal, Hop Sacre Coeur Montreal, Montreal, PQ, CanadaUniversidade Federal de São Paulo, Hosp Israelita Albert Einstein, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilWeb of Scienc

Utility of the ACC/AHA Lesion Classification to Predict Outcomes After Contemporary DES Treatment:Individual Patient Data Pooled Analysis From 7 Randomized Trials

BACKGROUND: Use of the modified American College of Cardiology (ACC)/American Heart Association (AHA) lesion classification as a prognostic tool to predict short‐ and long‐term clinical outcomes after percutaneous coronary intervention in the modern drug‐eluting stent era is uncertain. METHODS AND RESULTS: Patient‐level data from 7 prospective, randomized trials were pooled. Clinical outcomes of patients undergoing single lesion percutaneous coronary intervention with second‐generation drug‐eluting stent were analyzed according to modified ACC/AHA lesion class. The primary end point was target lesion failure (TLF: composite of cardiac death, target vessel myocardial infarction, or ischemia‐driven target lesion revascularization). Clinical outcomes to 5 years were compared between patients treated for noncomplex (class A/B1) versus complex (class B2/C) lesions. Eight thousand five hundred sixteen patients (age 63.1±10.8 years, 70.5% male) were analyzed. Lesions were classified as A, B1, B2, and C in 7.9%, 28.5%, 33.7%, and 30.0% of cases, respectively. Target lesion failure was higher in patients undergoing percutaneous coronary intervention of complex versus noncomplex lesions at 30 days (2.0% versus 1.1%, P=0.004), at 1 year (4.6% versus 3.0%, P=0.0005), and at 5 years (12.4% versus 9.2%, P=0.0001). By multivariable analysis, treatment of ACC/AHA class B2/C lesions was significantly associated with higher rate of 5‐year target lesion failure (adjusted hazard ratio, 1.39 [95% CI, 1.17–1.64], P=0.0001) driven by significantly higher rates of target vessel myocardial infarction and ischemia‐driven target lesion revascularization. CONCLUSIONS: In this pooled large‐scale analysis, treating complex compared with noncomplex lesions according to the modified ACC/AHA classification with second‐generation drug‐eluting stent was associated with worse 5‐year clinical outcomes. This historical classification system may be useful in the contemporary era for predicting early and late outcomes following percutaneous coronary intervention

Clinical Research on Transcatheter Aortic Valve Replacement for Bicuspid Aortic Valve Disease: Principles, Challenges, and an Agenda for the Future

Bicuspid aortic valve disease (BAVD) is present in up to half of all patients referred for surgical aortic valve replacement (SAVR) yet was an exclusion criterion for all randomized controlled trials (RCTs) comparing transcatheter aortic valve replacement (TAVR) to SAVR. Nonetheless, approximately 10% of patients currently treated with TAVR have BAVD and available observational data for performing TAVR in these patients are limited by selection bias. Many in the cardiovascular community have advocated for RCTs in this population, but none have been performed. The Heart Valve Collaboratory (HVC) is a multidisciplinary community of stakeholders with the aim of creating significant advances in valvular heart disease by stimulating clinical research, engaging in educational activities, and advancing regulatory science. In December 2020, the HVC hosted a Global Multidisciplinary workshop involving over 100 international experts in the field. Following this 2-day symposium, working groups with varied expertise were convened to discuss BAVD, including the need for and design of RCTs. This review, conducted under the auspices of the HVC, summarizes available data and knowledge gaps regarding procedural therapy for BAVD, outlining specific challenges for trials in this population. We also propose several potential studies that could be performed and discuss respective strengths and weaknesses of each approach. Finally, we present a roadmap for future directions in clinical research in TAVR for BAVD with an emphasis both on RCTs and also prospective registries focused on disease phenotyping to develop parameters and risk scores that could ultimately be applied to patients to inform clinical decision-making

COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up

Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, we review the current understanding of the pathogenesis, epidemiology, management and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, and of those with preexisting thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155446/1/Bikdeli-2020-COVID-19 and Thrombotic or Thromb.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155446/3/DeepBluepermissions_agreement-CCBYandCCBY-NC_ORCID_Barnes.docxhttps://deepblue.lib.umich.edu/bitstream/2027.42/155446/4/license_rdf.rdfDescription of Bikdeli-2020-COVID-19 and Thrombotic or Thromb.pdf : ArticleDescription of DeepBluepermissions_agreement-CCBYandCCBY-NC_ORCID_Barnes.docx : Deep Blue sharing agreemen

Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality among Patients with COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 � 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 �103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7) were included in the primary analysis (median interquartile range age, 62 50-71 years; 237 42.2% women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% 95% CI,-6.6% to 9.8%; odds ratio, 1.06 95% CI, 0.76-1.48; P =.70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% 1-sided 97.5% CI,-� to 3.4%; odds ratio, 1.83 1-sided 97.5% CI, 0.00-5.93), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% 95% CI, 0.4%-3.8%; P =.01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508. © 2021 American Medical Association. All rights reserved

DNA Polymerase POLN Participates in Cross-Link Repair and Homologous Recombination ▿ †

All cells rely on DNA polymerases to duplicate their genetic material and to repair or bypass DNA lesions. In humans, 16 polymerases have been identified, and each bears specific functions in genome maintenance. We identified here the recently discovered polymerase POLN to be involved in repair of DNA cross-links. Such DNA lesions are highly toxic and are believed to be repaired by the sequential activity of nucleotide excision repair, translesion synthesis, and homologous recombination mechanisms. By functionally assaying its role in these processes, we unraveled an unexpected involvement of POLN in homologous recombination. Moreover, we obtained evidence for physical and functional interaction of POLN with factors belonging to the Fanconi anemia pathway, a master regulator of cross-link repair. Finally, we show that POLN interacts and cooperates in DNA repair with the helicase HEL308, which shares a common origin with POLN in the Drosophila mus308 gene. Our data indicate that this novel polymerase-helicase complex participates in homologous recombination repair and is essential for cellular protection against DNA cross-links