Myocardial Bridging of Mid-left Anterior Descending Artery (LAD) Presenting As Transient Left Bundle Branch Block During Nuclear Stress Test.

Transient left bundle branch block occurring during a nuclear stress test in the setting of myocardial bridging is a relatively rare finding. We report a case of a 75-year-old male who presented with typical stable angina. Serial troponins were negative, and the electrocardiogram revealed normal sinus rhythm with left ventricular hypertrophy and T-wave inversions in the lateral leads. The nuclear stress test was non-ischemic but showed a transient left bundle branch block associated with chest pain and shortness of breath that occurred right after the administration of regadenoson. Coronary angiography revealed non-obstructive coronary artery disease and a mid-LAD myocardial bridge.

Second-generation everolimus-eluting intracoronary stents: a comprehensive review of the clinical evidence.

Percutaneous coronary intervention with implantation of second-generation drug-eluting stents (DES) has emerged as a mainstay for the treatment of obstructive coronary artery disease given its beneficial impact on clinical outcomes in these patients. Everolimus-eluting stents (EES) are one of the most frequently implanted second-generation DES; their use for the treatment of a wide range of patients including those with complex coronary lesions is supported by compelling evidence. Although newer stent platforms such as biodegradable polymer DES may lower local vessel inflammation, their efficacy and safety have not yet surpassed that of Xience stents. This article summarizes the properties of the Xience family of EES and the evidence supporting their use across diverse patient demographics and coronary lesion morphologies.

Patients with coronary artery disease (CAD) often require treatment for symptoms caused by blockages in coronary arteries. In addition to medical therapy, available procedure options include either coronary artery bypass grafting, a major heart surgery or percutaneous coronary intervention (PCI) with stenting. PCI is a minimally invasive procedure where a metallic stent (a mesh made up of fine metallic network in a tube shape used to keep vessels open) is advanced over a wire through an artery to open the coronary artery blockage. Over the past few decades, improvements in procedure technique and stent material have made PCI a highly safe and efficacious procedure. A newer generation of stents, known as drug-eluting stents (DES), have been developed in which metallic struts are covered with a highly biocompatible polymer (a thin material coating over the metallic mesh)  that releases drugs at the blockage site to prevent local cell growth in the vessel wall. Among the second-generation DES, Xience everolimus-eluting stents (EES) have shown better outcomes compared with earlier generations of stents. Another version of DES with biodegradable polymer coating is emerging but their advantage over EES remains uncertain. Currently, Xience EES are one of the most commonly used stents to treat CAD. This manuscript covers an in-depth review of clinical evidence on the performance of Xience stents in a diverse range patient populations.

Biolimus-eluting vs. other limus-eluting stents in NSTE-ACS: A pooled analysis of GLASSY and TWILIGHT.

BACKGROUND: Biodegradable polymer biolimus-eluting stents (BP-BES) may be associated with better outcomes in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) compared to other current-generation limus-eluting stents (LES). AIMS: To compare BP-BES with other current-generation LES in ACS patients undergoing PCI. METHODS: We pooled individual data of Non-ST-segment elevation (NSTE)-ACS patients from two large randomized controlled trials (GLASSY and TWILIGHT). The BP-BES groups consisted mostly of GLASSY patients, while the control group (other current-generation LES) included exclusively TWILIGHT patients. The primary outcome was major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, or stent thrombosis; the key secondary outcome was target-vessel failure (TVF). To account for trial design differences, outcomes were assessed at 3 months (short-term) and between 3 and 12 months (long-term) after PCI and subsequently pooled to estimate the 12-month hazards. RESULTS: Of 7107 and 6053 NSTE-ACS patients included in the short- and long-term analysis, 32.7% and 36.5% received a BP-BES, respectively. Risk of MACE associated with BP-BES versus other LES was similar at short-term (1.1% vs 1.3%, adjusted HR 0.86, 95%CI 0.53-1.38), lower at long-term (1.7% vs 3.1%, adjusted HR 0.49, 95%CI 0.34-0.72), and lower in the entire 12-month period (pooled adjusted HR 0.61, 95%CI 0.45-0.82). The cumulative 12-month risk of TVF was reduced with BP-BES (adjusted HR 0.52, 95%CI 0.38-0.70). CONCLUSION: BP-BES was associated with lower 12-month risks of MACE and TVF compared to other current generation LES among NSTE-ACS patients treated with abbreviated or standard ticagrelor-based DAPT. These non-randomized findings are hypothesis-generating. CONDENSED ABSTRACT: Differences in clinical outcomes may exist between biodegradable polymer biolimus-eluting stents (BP-BES) and other current-generation limus-eluting stent (LES) in patients with acute coronary syndrome (ACS). We pooled individual data of about 7000 Non-ST-segment elevation ACS patients undergoing PCI and treated with ticagrelor with or without aspirin from two large randomized controlled trials (GLASSY and TWILIGHT). BP-BES patients derived very largely from GLASSY and other LES patients from TWILIGHT. In this population, BP-BES compared to other current generation LES, were associated with a lower 12-month risk of major adverse cardiovascular events and target-vessel failure.

Unfolding of Imminent Bio-Signatures in the Prognosis of Thyroid Cancer; The Emergence of Estrogen Related Receptor Gamma (ERRγ) as a Hurricane.

Thyroid cancer's incidence has increased by leaps and bounds over the last years and accounts for 2.8% of new cases of cancers. This increasing bar is partially assisted by enormous screening to understand the sub-clinical status. Advanced tumor growth is the leading cause of thyroid cancer-associated death. However, the complete understanding of the underlying cause is still to be disclosed. The updated clinical assessment evidenced a few major oncogenes viz. RAS, BRAF, and RET as key drivers in the development and progression of thyroid cancer. The BRAF mutation, a major cause of aggressive tumor type in papillary thyroid carcinoma, is frequently reported. The characteristic oncogenic changes imply thyroid cancer to be clinically an ideal model for targeted therapy against RET, RAS, and BRAF mutation. Though the sensitive biochemical marker assay has been improvised, the diagnosis of thyroid follicular neoplasms is still a big challenge as the biopsy aspiration cannot define the nature of the tumor in 30% of the cases. The main hurdle is assisted distinction between follicular thyroid lesions. The discrimination between follicular thyroid adenomas and carcinomas is histologically accomplished. This strictly necessitates the identification of sensitive diagnostic/prognostic markers to mitigate the risk of thyroid cancer and to avoid the unnecessary hurdles of biopsy and surgery. An array of prognostic biomarkers is being used for the diagnosis of thyroid cancer. However, Estrogen Related Receptor Gamma (ERRγ) is setting a new benchmark among the clinical biomarkers. The dramatic expression of ERRγ in thyroid cancer enables itself not only to serve as a characteristic diagnostic marker but also as a therapeutic target. Recently, we have reported that ERRγ is upregulated in 96 papillary thyroid cancer (PTC) and 26 poorly differentiated/ anaplastic thyroid cancer (ATC) samples. Various synthetic ERRγ inverse agonists viz. GSK5182, DN200434, and 24e are fully proved to modulate ERRγ expression in ATC to attain partial cure. If this finding can be assayed on a larger scale the evaluation of this marker may be warranted and informative. This review article highlights the ascending sheds of clinical biomarkers of thyroid cancer. This also reveals the clinical importance of ERRγ as an evolving diagnostic and therapeutic target in thyroid cancer.

Unsung versatility of elastin-like polypeptide inspired spheroid fabrication: A review.

Lately, 3D cell culture technique has gained a lot of appreciation as a research model. Augmented with technological advancements, the area of 3D cell culture is growing rapidly with a diverse array of scaffolds being tested. This is especially the case for spheroid cultures. The culture of cells as spheroids provides opportunities for unanticipated vision into biological phenomena with its application to drug discovery, metabolic profiling, stem cell research as well as tumor, and disease biology. Spheroid fabrication techniques are broadly categorised into matrix-dependent and matrix-independent techniques. While there is a profusion of spheroid fabrication substrates with substantial biological relevance, an economical, modular, and bio-compatible substrate for high throughput production of spheroids is lacking. In this review, we posit the prospects of elastin-like polypeptides (ELPs) as a broad-spectrum spheroid fabrication platform. Elastin-like polypeptides are nature inspired, size-tunable genetically engineered polymers with wide applicability in various arena of biological considerations, has been employed for spheroid culture with profound utility. The technology offers a cheap, high-throughput, reproducible alternative for spheroid culture with exquisite adaptability. Here, we will brief the applicability of 3D cultures as compared to 2D cultures with spheroids being the focal point of the review. Common approaches to spheroid fabrication are discussed with existential limitations. Finally, the versatility of elastin-like polypeptide inspired substrates for spheroid culture has been discussed.

Influence of Race/Ethnicity and Sex on Coronary Stent Outcomes in Diabetic Patients.

Background: How diabetes mellitus (DM), race/ethnicity, and sex impact ischemic events following coronary artery stent procedures is unknown. Methods: Using the PLATINUM Diversity and PROMUS Element Plus Post-Approval Pooled Study (N = 4184), we examined the impact of race/ethnicity, sex, and DM on coronary stent outcomes. Primary outcome was 1-year major adverse cardiac events (MACE) (MACE composite: death, myocardial infarction [MI], and target vessel revascularization). Results: The study sample included 1437 diabetic patients (501 White men, 470 White women, 246 minority men, 220 minority women) and 2641 patients without medically treated DM (561 minority, 1090 women). Mean age (years) ranged from 61 in minority men to 65 in White women. Diabetic patients had a higher prevalence of atherosclerotic risk factors and comorbidities. Diabetic minority women (DMW; 70% Black, 27% Hispanic) had similar atherosclerotic risk factors to other diabetics, but experienced higher 1-year MACE (14.4% vs 7.5%, P <.01) and MI (4.3% vs 1.6%, P <.01) rates compared with patients without medically treated DM. No other diabetic cohort (White men, White women, minority men) showed an increased risk of MACE vs patients without medically treated DM. The incremental risk of MACE in DMW was associated with insulin use and persisted after risk adjustment (adjusted odds ratio 1.6 vs patients without medically treated DM; 95% CI, 1.0-2.5). Independent predictors of 1-year MACE included insulin use, hyperlipidemia, renal disease, and prior MI. Conclusions: DMW face the highest risk of ischemic events following coronary stenting, driven, in part, by insulin use. Aggressive secondary prevention and strict glycemic control are imperative in this cohort, and further research is warranted to elucidate the biologic mechanisms underpinning these observations. Clinical Trial Registration: NCT02240810 (http://clinicaltrials.gov/).

Antithrombotic strategy variability in atrial fibrillation and obstructive coronary disease revascularised with percutaneous coronary intervention: primary results from the AVIATOR 2 international registry.

BACKGROUND: Managing percutaneous coronary intervention (PCI) patients with atrial fibrillation (AF) presents challenges given that there are several potential antithrombotic therapy (ATT) strategies. AIMS: We examined ATT patterns, agreement between subjective physician ratings and validated risk scores, physician-patient perceptions influencing ATT and 1-year outcomes. METHODS: The AVIATOR 2 prospective registry enrolled 514 non-valvular AF-PCI patients from 11 sites. Treating physicians selected ATT and completed smartphone surveys rating stroke and bleeding risks, compared against CHA2DS2-VASc and HAS-BLED scores. Patients completed surveys regarding treatment understanding. Primary outcomes were 1-year major adverse cardiac or cerebrovascular events (MACCE: composite of death, myocardial infarction, definite/probable stent thrombosis, stroke, target lesion revascularisation) and actionable bleeding (Bleeding Academic Research Consortium 2, 3 or 5). RESULTS: The mean patient age was 73.2±9.0 years, including 25.8% females. Triple therapy (TT: 1 anticoagulant and 2 antiplatelet agents) was prescribed in 66.5%, dual antiplatelet therapy (DAPT) in 20.7% and dual therapy (1 anticoagulant+1 antiplatelet agent) in 12.8% of patients. Physician ratings and validated risk scores showed poor agreement (stroke: kappa=0.03; bleeding: kappa=0.07). Physicians rated bleeding-related safety (93.8%) as the main factor affecting ATT choice. Patients worried about stroke over bleeding (50.6% vs 14.8%). No group differences by ATT strategy were observed in 1-year MACCE (TT 14.1% vs dual therapy 12.7% vs DAPT 18.5%; p=0.25), or actionable bleeding (14.7% vs 7.9% vs 15.1%, respectively; p=0.89). CONCLUSIONS: The AVIATOR 2 study is the first digital health study examining physician-patient perspectives on ATT choices after AF-PCI. TT was the most common strategy without differences in 1-year outcomes in ATT strategy. Physicians rated safety first when prescribing ATT; patients feared stroke over bleeding. CLINICALTRIALS: gov: NCT02362659.

Ticagrelor With or Without Aspirin in Chinese Patients Undergoing Percutaneous Coronary Intervention: A TWILIGHT China Substudy.

BACKGROUND: The risk/benefit tradeoff of dual antiplatelet therapy after percutaneous coronary intervention may vary in East Asian patients as compared with their non-East Asian counterparts. METHODS: The double-blind, placebo-controlled, randomized TWILIGHT trial (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) enrolled patients undergoing high-risk percutaneous coronary intervention. After 3 months of treatment with ticagrelor plus aspirin, event-free and adherent patients remained on ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding; the key secondary end point was the first occurrence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: Of 9006 enrolled and 7119 randomized patients in TWILIGHT, 1169 patients (13.0%) were enrolled at 27 Chinese sites in this prespecified substudy, of whom 1028 (14.4%) patients were randomized after 3 months. The incidence of the primary end point was 6.2% in the ticagrelor+aspirin group versus 3.5% in the ticagrelor+placebo group between randomization and 1 year (hazard ratio, 0.56 [95% CI, 0.31-0.99]; P=0.048). The key secondary end point occurred in 3.4% of patients in the ticagrelor+aspirin group versus 2.4% in the ticagrelor+placebo group (hazard ratio, 0.70 [95% CI, 0.33-1.46]; P=0.34). There was no interaction between the region of randomization (China versus the rest of the world) and randomized treatment assignment in terms of the primary or key secondary end points. CONCLUSIONS: Ticagrelor monotherapy significantly reduced clinically relevant bleeding without increasing ischemic events as compared with ticagrelor plus aspirin in Chinese patients undergoing high-risk percutaneous coronary intervention. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02270242.

Application of elastin-like polypeptide (ELP) containing extra-cellular matrix (ECM) binding ligands in regenerative medicine.

Extracellular matrix (ECM) molecules play an important role in regulating molecular signaling associated with proliferation, migration, differentiation, and tissue repair. The identification of new kinds of ECM mimic biomaterials to recapitulate critical functions of biological systems are important for various applications in tissue engineering and regenerative medicine. The use of human elastin derived materials with controlled biological properties and other functionalities to improve their cell-response was proposed. Herein, we reported genetic encoded synthesis of ELP (elastin-like polypeptide) containing ECM domains like RGD (integrin binding ligand) and YIGSR (laminin-selective receptor binding ligand) to regulate cell behaviour in more complex ways, and also better model natural matrices. Thermal responsiveness of the ELPs and structural conformation were determined to confirm its phase transition behaviour. The fusion ELPs derivatives were analysed for mechanical involvement of growth mechanism, regenerative, and healing processes. The designed fusion ELPs promoted fast and strong attachment of fibroblast cells. The fusion ELP derivatives enhanced the migration of keratinocyte cells which of crucial for wound healing. Together it provides a profound matrix for endothelial cells and significantly enhanced tube formation of HUVEC cells. Thus, strategy of using cell adhesive ELP biopolymer emphasizing the role of bioactive ELPs as next generation skin substitutes for regenerative medicine.

Impact of Race/Ethnicity on Long Term Outcomes After Percutaneous Coronary Intervention with Drug-Eluting Stents.

Cardiovascular disease constitutes the leading cause of mortality worldwide, irrespective of race/ethnicity. Previous studies have shown that minority patients with acute coronary syndrome have distinct clinical, anatomic, and socioeconomic characteristics which may affect clinical outcomes. We included patients who underwent percutaneous coronary intervention with drug-eluting stents for ST-segment elevation myocardial infarction (STEMI), non-STEMI, or unstable angina in a single center. Patients were stratified into Caucasian, African-American, Hispanic, and Asian. Caucasians were the reference group. The primary end point was major adverse cardiac and cerebrovascular events, composite of death, spontaneous myocardial infarction, or stroke at 1 year. Of 6,800 patients included, 49.7% were Caucasian, 20.7% Hispanic, 17.0% Asian and 12.6% African-American. Caucasians were the oldest, Hispanics and Asians had the highest prevalence of diabetes mellitus whereas African-Americans had more chronic kidney disease. Hispanics and African-Americans had the highest STEMI rates, whereas Asians were more likely to present with unstable angina. Compared with Caucasians, Asians had a lower rate of major adverse cardiac and cerebrovascular events at 1 year (3.9% vs 7.1%; p <0.01) whereas Hispanics (6.2% vs 7.1%; p = 0.17) and African-Americans (8.0% vs 7.1%; p = 0.38) had comparable outcomes. Differences were driven by mortality. Findings remained unchanged after adjustment. In conclusion, in acute coronary syndrome patients who underwent percutaneous coronary intervention, Asian race/ethnicity was associated with favorable cardiovascular outcomes compared with Caucasians. No significant differences were observed for Hispanics and African-Americans.

Perioperative risk and antiplatelet management in patients undergoing non-cardiac surgery within 1 year of PCI.

Perioperative cardiovascular complications are important causes of morbidity and mortality associated with non-cardiac surgery, especially in patients with recent percutaneous coronary intervention (PCI). We aimed to illustrate the types and timing of different surgeries occurring after PCI, and to evaluate the risk of thrombotic and bleeding events according to the perioperative antiplatelet management. Patients undergoing urgent or elective non-cardiac surgery within 1 year of PCI at a tertiary-care center between 2011 and 2018 were included. The primary outcome was major adverse cardiac events (MACE; composite of death, myocardial infarction, or stent thrombosis) at 30 days. Perioperative bleeding was defined as ≥ 2 units of blood transfusion. A total of 1092 surgeries corresponding to 747 patients were classified by surgical risk (low: 50.9%, intermediate: 38.4%, high: 10.7%) and priority (elective: 88.5%, urgent/emergent: 11.5%). High-risk and urgent/emergent surgeries tended to occur earlier post-PCI compared to low-risk and elective ones, and were associated with an increased risk of both MACE and bleeding. Preoperative interruption of antiplatelet therapy (of any kind) occurred in 44.6% of all NCS and was more likely for procedures occurring later post-PCI and at intermediate risk. There was no significant association between interruption of antiplatelet therapy and adverse cardiac events. Among patients undergoing NCS within 1 year of PCI, perioperative ischemic and bleeding events primarily depend on the estimated surgical risk and urgency of the procedure, which are increased early after PCI. Preoperative antiplatelet interruption was not associated with an increased risk of cardiac events.

Safety and efficacy of ticagrelor monotherapy according to drug-eluting stent type: the TWILIGHT-STENT study.

BACKGROUND: In the TWILIGHT trial, ticagrelor monotherapy after a short course of dual antiplatelet therapy (DAPT) was shown to be a safe bleeding avoidance strategy in high-risk patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). AIMS: The aim of this study was to evaluate the effects of ticagrelor monotherapy after three-month DAPT in patients undergoing PCI, according to DES type. METHODS: In the current sub-analysis from TWILIGHT, patients were stratified into three groups based on DES type: durable polymer everolimus-eluting stents (DP-EES), durable polymer zotarolimus-eluting stents (DP-ZES), and biodegradable polymer DES (BP-DES). Bleeding and ischaemic outcomes were assessed at one year after randomisation. RESULTS: Out of 5,769 patients, 3,014 (52.2%) had DP-EES, 1,350 (23.4%) had DP-ZES and 1,405 (24.4%) had BP-DES. Compared with ticagrelor plus aspirin, ticagrelor monotherapy had significantly lower BARC type 2, 3 or 5 bleeding compared with DAPT; DP-EES (3.8% vs 6.7%; HR 0.56, 95% CI: 0.41-0.78), DP-ZES (4.6% vs 6.9%; HR 0.66, 95% CI: 0.42-1.04) and BP-DES (4.2% vs 7.9%; HR 0.52, 95% CI: 0.33-0.81; pinteraction=0.76). Ticagrelor monotherapy resulted in similar rates of death, MI, or stroke: DP-EES (4.2% vs 4.3%; HR 0.97; 95% CI: 0.68-1.37); DP-ZES (4.1% vs 3.1%; HR 1.32; 95% CI: 0.75-2.33); BP-DES (3.9% vs 4.2%; HR 0.92; 95% CI: 0.54-1.55; pinteraction=0.60). In both unadjusted and covariate-adjusted analyses, DES type was not associated with any differences in ischaemic or bleeding complications. CONCLUSIONS: As compared with ticagrelor plus aspirin, ticagrelor monotherapy after a short DAPT duration lowered bleeding complications without increasing the ischaemic risk, irrespective of DES type. We observed no significant differences among DES types.

Incidence, predictors and clinical impact of permanent pacemaker insertion in women following transcatheter aortic valve implantation: Insights from a prospective multinational registry.

OBJECTIVES: To describe the incidence, predictors, and clinical impact of permanent pacemaker insertion (PPI) following transcatheter aortic valve replacement (TAVR) in women. BACKGROUND: Data on pacemaker insertion complicating TAVR in women are scarce. METHODS: The Women's International Transcatheter Aortic Valve implantation (WIN-TAVI) is a prospective registry evaluating the safety and efficacy of TAVR in women. We included patients without preprocedural pacemakers and divided them into two groups: (1) PPI and (2) no-PPI. We identified PPI predictors using logistic regression and studied its clinical impact on the Valve Academic Research Consortium (VARC)-2 efficacy and safety endpoints. RESULTS: Out of 1019 patients, 922 were included in the analysis. Post-TAVR PPI occurred in 132 (14.3%) patients. Clinical and procedural characteristics were similar in both groups. Pre-existing right bundle branch block (RBBB) was associated with a high risk of post-TAVR PPI (OR 3.62, 95% CI 1.85-7.06, p < 0.001), while implantation of balloon-expandable prosthesis was associated with a lower risk (OR 0.47, 95% CI 0.30-0.74, p < 0.001). Post-TAVR PPI prolonged in-hospital stay by a median of 2 days (11 [9-16] days in PPI vs. 9 [7-14] days in no-PPI, p = 0.005), yet risks of VARC-2 efficacy and safety endpoints at 1 year were similar in both groups (adj HR 0.95, 95% CI 0.60-1.52, p = 0.84 and adj HR 1.22, 95% CI 0.83-1.79, p = 0.31, respectively). CONCLUSION: Pacemaker implantation following TAVR is frequent among women and is associated with pre-existing RBBB and valve type. PPI prolongs hospital stay, albeit without any significant impact on 1-year outcomes.

Electrical Storm With Incessant Ventricular Tachycardia in a COVID-19 Patient: Review of Current Evidence.

Coronavirus disease 2019 (COVID-19) is associated with various cardiovascular manifestations, including myocarditis, myocardial infarction, and arrhythmias. A prothrombotic state is the primary underlying pathogenic mechanism. While cardiac arrhythmias manifest more commonly amongst critically ill COVID-19 populations, ventricular arrhythmias have been reported only in few cases. This report describes a case of a 95-year-old African American man with COVID-19, who developed sustained monomorphic ventricular tachycardia, which progressed to an electrical storm. The case highlights the importance of high clinical suspicion, early recognition of electrical abnormalities in patients with active COVID-19 infection, and its ability to precipitate fatal ventricular arrhythmia. Also, we provide a literature review on the electrical storm in COVID-19 patients, highlighting the pathophysiologic mechanisms and the management of this deadly arrhythmia.

Impact of sex on long-term cardiovascular outcomes of patients undergoing percutaneous coronary intervention for acute coronary syndromes.

BACKGROUND: Women with acute coronary syndrome (ACS) generally present with more comorbidities and experience worse clinical outcomes compared with males. However, it is unclear whether this represents genuine sex-related difference or stems from clinical, procedural and socioeconomic factors. METHODS: We analyzed consecutive patients undergoing percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), non-STEMI or unstable angina at a single tertiary-care center. Exclusion criteria were unknown sex, age < 18 years and PCI with bare metal stent or without stent placement. The study population was stratified according to sex. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) defined as the composite of death, spontaneous myocardial infarction, or stroke at 1 year. Secondary endpoints were individual components of MACCE, target vessel revascularization (TVR) and clinically significant bleeding. RESULTS: Of the 7362 patients included, 5031 (68.3%) were men and 2331 (31.7%) women. Women were older and presented with a higher burden of comorbidities while men had more complex coronary anatomy. The incidence of 1 year MACCE was significantly higher among women (8.0% versus 5.6%; p < 0.01) compared to men. Women also experienced a higher rate of bleeding (2.3% vs. 1.4%; p = 0.02) while there were no differences between groups in terms of TVR (8.1% vs. 7.8%; p-value = 0.83). Differences in outcomes were attenuated after multivariable adjustment. Findings were consistent across ACS subgroups. CONCLUSIONS: In a contemporary ACS population treated with drug-eluting stents, women experienced a higher crude rate of 1-year MACCE. This was no longer apparent after accounting for baseline imbalances.

Sex Differences Among Patients With High Risk Receiving Ticagrelor With or Without Aspirin After Percutaneous Coronary Intervention: A Subgroup Analysis of the TWILIGHT Randomized Clinical Trial.

Importance: Shortened dual antiplatelet therapy followed by potent P2Y12 receptor inhibitor monotherapy reduces bleeding without increasing ischemic events after percutaneous coronary intervention (PCI). Objective: To explore sex differences and evaluate the association of sex with outcomes among patients treated with ticagrelor monotherapy vs ticagrelor plus aspirin. Design, Setting, and Participants: This was a prespecified secondary analysis of TWILIGHT, an investigator-initiated, placebo-controlled randomized clinical trial conducted at 187 sites across 11 countries. Study participants included patients who underwent successful PCI with drug-eluting stents, were planned for discharge with ticagrelor plus aspirin, and who had at least 1 clinical and at least 1 angiographic feature associated with high risk of ischemic or bleeding events. Data were analyzed from May to July 2020. Interventions: At 3 months after PCI, patients adherent to ticagrelor and aspirin without major adverse event were randomized to either aspirin or placebo for an additional 12 months along with ticagrelor. Main Outcomes and Measures: The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding at 12 months after randomization. The primary ischemic end point was a composite of death, myocardial infarction, or stroke. Results: Of 9006 enrolled patients, 7119 underwent randomization (mean [SD] age, 63.9 [10.2] years; 5421 [76.1%] men). Women were older (mean [SD] age, 65.5 [9.6] years in women vs 63.4 [10.3] years in men) with higher prevalence of chronic kidney disease (347 women [21.2%] vs 764 men [14.7%]). The primary bleeding end point occurred more often in women than men (hazard ratio [HR], 1.32; 95% CI, 1.06-1.64; P = .01). After multivariate adjustment, incremental bleeding risk associated with female sex was no longer significant (adjusted HR, 1.20; 95% CI, 0.95-1.52; P = .12). Ischemic end points were similar between sexes. Ticagrelor plus placebo vs ticagrelor plus aspirin was associated with lower risk of BARC type 2, 3, or 5 bleeding in women (adjusted HR, 0.62; 95% CI, 0.42-0.92; P = .02) and men (adjusted HR, 0.57; 95% CI, 0.44-0.73; P < .001; P for interaction = .69). Ischemic end points were similar between treatment groups in both sexes. Conclusions and Relevance: These findings suggest that the higher bleeding risk in women compared with men was mostly attributable to baseline differences, whereas ischemic events were similar between sexes. In this high-risk PCI population, the benefits of early aspirin withdrawal with continuation of ticagrelor were generally comparable in women and men. Trial Registration: ClinicalTrials.gov Identifier: NCT02270242.

Radial versus femoral access for coronary interventions: An updated systematic review and meta-analysis of randomized trials.

OBJECTIVE: It is still debated if benefits associated with radial versus femoral access for coronary angiography and percutaneous coronary interventions (PCI) are due to the access site selection itself, operator expertise or other underlying mechanisms. METHODS: We searched PubMed, Embase, and meeting abstracts for randomized trials comparing radial versus femoral access site for coronary angiography and PCI. Primary safety endpoint was major bleeding. Coprimary efficacy endpoints were stroke and myocardial infarction (MI). This study is registered with PROSPERO. RESULTS: We identified 31 trials (30,096 patients, PCI performed in 21,225 patients). Radial compared to femoral access was associated with a significant risk reduction in major bleeding (OR 0.53, 95%CI 0.42-0.66, I2  = 3.3%). Findings were consistent regardless of clinical characteristics or whether coronary angiography was performed with or without PCI. The benefit of radial access was significantly increased in studies published before 2010 and in patients with chronic coronary syndrome. Risk for stroke (OR 1.11, 95%CI 0.76-1.64, I2  = 0%) and MI (OR 0.90, 95%CI 0.79-1.04, I2  = 0%) were comparable between the groups. Risk for mortality and vascular complications were significantly lower with radial than femoral access. CONCLUSION: In patients undergoing coronary angiography and PCI, radial access is associated with a significant risk reduction in bleeding, vascular complications, and mortality compared to femoral access. The risk of stroke or MI were comparable in patients with radial or femoral access.

Impact of diabetes mellitus on female subjects undergoing transcatheter aortic valve implantation: Insights from the WIN-TAVI international registry.

BACKGROUND: Female subjects constitute half of all transcatheter aortic valve implantation (TAVI) candidates, but the association between important comorbidities such as diabetes mellitus (DM) and clinical outcomes after TAVI remains unclear in this group. METHOD: WIN-TAVI is a real-world international registry of exclusively female subjects undergoing TAVI. The study population was stratified into those with (DM) and those without DM (NDM). Valve Academic Research Consortium (VARC)-2 efficacy (composite of all-cause death, stroke, myocardial infarction, hospitalization for valve-related symptoms or worsening congestive heart failure, or valve-related dysfunction) was the primary endpoint for this analysis. RESULTS: Of the 1012 subjects included in this study, 264 (26.1%) had DM at baseline. DM patients were younger but had a higher burden of comorbidities. There were no differences in VARC-2 efficacy events between DM and NDM patients at 30 days or 1 year. Conversely, patients with DM had a lower risk of VARC-2 life threatening bleeding at 30 days and 1 year after TAVI compared to NDM patients, which remained significant even after multivariable adjustment (HR, 0.34, 95% CI, 0.12-0.99; p = .047). In the subgroup analysis, insulin-dependent DM was not associated with an increased risk of adverse outcomes. CONCLUSIONS: Among female patients undergoing TAVI, more than one-fourth of the subjects presented with DM. At 1-year follow-up, DM was associated with lower bleeding complications and no increase in the risk of other adverse events, including mortality, after TAVI.

Preprocedural anemia in females undergoing transcatheter aortic valve implantation: Insights from the WIN-TAVI registry.

OBJECTIVES: To assess the impact of anemia on clinical outcomes in female patients enrolled in the Women's InterNational transcatheter aortic valve implantation (WIN-TAVI) registry. BACKGROUND: Anemia is highly prevalent among females who constitute half of TAVI candidates, yet, its clinical significance remains poorly investigated. METHODS: Patients were divided into three groups according to preprocedural hemoglobin (Hb) level: (1) no anemia (Hb ≥12 g/dl), (2) mild-to-moderate anemia (10 ≤ Hb <12 g/dl), and (3) severe anemia (Hb <10 g/dl). The primary outcome was the occurrence of Valve Academic Research Consortium (VARC)-2 efficacy endpoint, a composite of mortality, stroke, myocardial infarction (MI), hospitalization for valve-related symptoms or heart failure or valve-related dysfunction at 1-year follow-up. RESULTS: Hemoglobin level was available in 877 (86.1%) patients: 412 (47.0%) had no anemia, 363 (41.4%) had mild-to-moderate anemia, and 102 (11.6%) had severe anemia. The latter group had a higher prevalence of cardiovascular risk factors. Compared with patients without anemia, severe anemia was associated with a greater risk of VARC-2 efficacy endpoint (adj HR 1.71, 95% CI: 1.02-2.87, p = .04), all-cause death (adj HR 2.36, 95% CI: 1.31-4.26, p = .004) and a composite of death, MI or stroke (adj HR 1.88, 95% CI: 1.10-3.22, p = .02) at 1 year. Moreover, an increased risk of late mortality (adj HR 1.15, 95% CI: 1.02-1.30, p = .03) was observed with every 1 g/dl decrease in hemoglobin level. CONCLUSION: Severe anemia in females undergoing TAVI was independently associated with increased rates of VARC-2 efficacy endpoint and mortality at 1 year.