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IMPORTANCE: Two initial sham-controlled trials demonstrated that ultrasound renal denervation decreases blood pressure (BP) in patients with mild to moderate hypertension and hypertension that is resistant to treatment. OBJECTIVE: To study the efficacy and safety of ultrasound renal denervation without the confounding influence of antihypertensive medications in patients with hypertension. DESIGN, SETTING, AND PARTICIPANTS: Sham-controlled, randomized clinical trial with patients and outcome assessors blinded to treatment assignment that was conducted between January 14, 2019, and March 25, 2022, at 37 centers in the US and 24 centers in Europe, with randomization stratified by center. Patients aged 18 years to 75 years with hypertension (seated office systolic BP [SBP] ≥140 mm Hg and diastolic BP [DBP] ≥90 mm Hg despite taking up to 2 antihypertensive medications) were eligible if they had an ambulatory SBP/DBP of 135/85 mm Hg or greater and an SBP/DBP less than 170/105 mm Hg after a 4-week washout of their medications. Patients with an estimated glomerular filtration rate of 40 mL/min/1.73 m2 or greater and with suitable renal artery anatomy were randomized 2:1 to undergo ultrasound renal denervation or a sham procedure. Patients were to abstain from antihypertensive medications until the 2-month follow-up unless prespecified BP criteria were exceeded and were associated with clinical symptoms. INTERVENTIONS: Ultrasound renal denervation vs a sham procedure. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was the mean change in daytime ambulatory SBP at 2 months. The primary safety composite outcome of major adverse events included death, kidney failure, and major embolic, vascular, cardiovascular, cerebrovascular, and hypertensive events at 30 days and renal artery stenosis greater than 70% detected at 6 months. The secondary outcomes included mean change in 24-hour ambulatory SBP, home SBP, office SBP, and all DBP parameters at 2 months. RESULTS: Among 1038 eligible patients, 150 were randomized to ultrasound renal denervation and 74 to a sham procedure (mean age, 55 years [SD, 9.3 years]; 28.6% female; and 16.1% self-identified as Black or African American). The reduction in daytime ambulatory SBP was greater with ultrasound renal denervation (mean, -7.9 mm Hg [SD, 11.6 mm Hg]) vs the sham procedure (mean, -1.8 mm Hg [SD, 9.5 mm Hg]) (baseline-adjusted between-group difference, -6.3 mm Hg [95% CI, -9.3 to -3.2 mm Hg], P

Supplemental material, sj-pdf-1-vmj-10.1177_1358863X231157441 for Association between Hispanic or Latino ethnicity and pulmonary embolism severity, management, and in-hospital outcomes by Daniel J Snyder, Robert S Zilinyi, Mahesh V Madhavan, Marissa Alsaloum, Danial Saleem, John J Buyske, Emma W Healy, Maxine J McGredy, Bernardo T Da Silva, Erika B Rosenzweig, Koji Takeda, Daniel Brodie, Cara Agerstrand, Andrew Eisenberger, Ajay J Kirtane, Sahil A Parikh and Sanjum S Sethi in Vascular Medicine

Supplemental material, sj-pdf-1-vmj-10.1177_1358863X231157441 for Association between Hispanic or Latino ethnicity and pulmonary embolism severity, management, and in-hospital outcomes by Daniel J Snyder, Robert S Zilinyi, Mahesh V Madhavan, Marissa Alsaloum, Danial Saleem, John J Buyske, Emma W Healy, Maxine J McGredy, Bernardo T Da Silva, Erika B Rosenzweig, Koji Takeda, Daniel Brodie, Cara Agerstrand, Andrew Eisenberger, Ajay J Kirtane, Sahil A Parikh and Sanjum S Sethi in Vascular Medicine

Auteurs : RADIANCE-HTN Investigators; International audience; Importance Although early trials of endovascular renal denervation (RDN) for patients with resistant hypertension (RHTN) reported inconsistent results, ultrasound RDN (uRDN) was found to decrease blood pressure (BP) vs sham at 2 months in patients with RHTN taking stable background medications in the Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN TRIO) trial. Objectives To report the prespecified analysis of the persistence of the BP effects and safety of uRDN vs sham at 6 months in conjunction with escalating antihypertensive medications. Design, Setting, and Participants This randomized, sham-controlled, clinical trial with outcome assessors and patients blinded to treatment assignment, enrolled patients from March 11, 2016, to March 13, 2020. This was an international, multicenter study conducted in the US and Europe. Participants with daytime ambulatory BP of 135/85 mm Hg or higher after 4 weeks of single-pill triple-combination treatment (angiotensin-receptor blocker, calcium channel blocker, and thiazide diuretic) with estimated glomerular filtration rate (eGFR) of 40 mL/min/1.73 m 2 or greater were randomly assigned to uRDN or sham with medications unchanged through 2 months. From 2 to 5 months, if monthly home BP was 135/85 mm Hg or higher, standardized stepped-care antihypertensive treatment starting with aldosterone antagonists was initiated under blinding to treatment assignment. Interventions uRDN vs sham procedure in conjunction with added medications to target BP control. Main Outcomes and Measures Six-month change in medications, change in daytime ambulatory systolic BP, change in home systolic BP adjusted for baseline BP and medications, and safety. Results A total of 65 of 69 participants in the uRDN group and 64 of 67 participants in the sham group (mean [SD] age, 52.4 [8.3] years; 104 male [80.6%]) with a mean (SD) eGFR of 81.5 (22.8) mL/min/1.73 m 2 had 6-month daytime ambulatory BP measurements. Fewer medications were added in the uRDN group (mean [SD], 0.7 [1.0] medications) vs sham (mean [SD], 1.1 [1.1] medications; P = .045) and fewer patients in the uRDN group received aldosterone antagonists at 6 months (26 of 65 [40.0%] vs 39 of 64 [60.9%]; P = .02). Despite less intensive standardized stepped-care antihypertensive treatment, mean (SD) daytime ambulatory BP at 6 months was 138.3 (15.1) mm Hg with uRDN vs 139.0 (14.3) mm Hg with sham (additional decreases of −2.4 [16.6] vs −7.0 [16.7] mm Hg from month 2, respectively), whereas home SBP was lowered to a greater extent with uRDN by 4.3 mm Hg (95% CI, 0.5-8.1 mm Hg; P = .03) in a mixed model adjusting for baseline and number of medications. Adverse events were infrequent and similar between groups. Conclusions and Relevance In this study, in patients with RHTN initially randomly assigned to uRDN or a sham procedure and who had persistent elevation of BP at 2 months after the procedure, standardized stepped-care antihypertensive treatment escalation resulted in similar BP reduction in both groups at 6 months, with fewer additional medications required in the uRDN group. Trial Registration ClinicalTrials.gov Identifier: NCT02649426

ImportanceUltrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency of the uRDN effect across the HTN spectrum is clinically important.ObjectiveTo characterize the effectiveness and safety of uRDN vs a sham procedure from individual patient-level pooled data across uRDN trials including either patients with mild to moderate HTN on a background of no medications or with HTN resistant to standardized triple-combination therapy.Data SourcesA Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN SOLO and TRIO) and A Study of the ReCor Medical Paradise System in Stage II Hypertension (RADIANCE II) trials.Study SelectionTrials with similar designs, standardized operational implementation (medication standardization and blinding of both patients and physicians to treatment assignment), and follow-up.Data Extraction and SynthesisPooled analysis using individual patient-level data using linear regression models to compare uRDN with sham across the trials.Main Outcomes and MeasuresThe primary outcome was baseline-adjusted change in 2-month daytime ambulatory systolic BP (dASBP) between groups.ResultsA total of 506 patients were randomized in the 3 studies (uRDN, 293; sham, 213; mean [SD] age, 54.1 [9.3]; 354 male [70.0%]). After a 1-month medication stabilization period, dASBP was similar between the groups (mean [SD], uRDN, 150.3 [9.2] mm Hg; sham, 150.8 [10.5] mm Hg). At 2 months, dASBP decreased by 8.5 mm Hg to mean (SD) 141.8 (13.8) mm Hg among patients treated with uRDN and by 2.9 mm Hg to 147.9 (14.6) mm Hg among patients treated with a sham procedure (mean difference, −5.9; 95% CI, −8.1 to −3.8 mm Hg; P Conclusions and RelevanceResults of this patient-level pooled analysis suggest that BP reductions with uRDN were consistent across HTN severity in sham-controlled trials designed with a 2-month primary end point to standardize medications across randomized groups.Trial RegistrationClinicalTrials.gov Identifier: NCT02649426 and NCT03614260

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The pulmonary artery (PA) catheter can be a useful tool in the management of patients with cardiogenic shock; however, there are challenges with the use of this catheter, and clinicians must balance the risks and benefits. In addition, clinicians must properly interpret data generated from a PA catheter in the context of other data to optimize a patient's hemodynamics., Kirtane, Ajay J. (2022) "Role of Invasive Hemodynamics in Shock Management: Is a Pulmonary Artery Catheter Always Necessary?," Journal of Shock and Hemodynamics: Vol. 1(2) :E2022121

The treatment of left main (LM) coronary artery disease (CAD) requires complex decision-making. Recent clinical practice guidelines provide clinicians with guidance; however, decisions regarding treatment for individual patients can still be difficult. The American College of Cardiology's Cardiac Surgery Team and Interventional Council joined together to develop a practical approach to the treatment of LM CAD, taking into account randomized clinical trial, meta-analyses, and clinical practice guidelines. The various presentations of LM CAD based on anatomy and physiology are presented. Recognizing the complexity of LM CAD, which rarely presents isolated and is often in combination with multivessel disease, a treatment algorithm with medical therapy alone or in conjunction with percutaneous coronary intervention or coronary artery bypass grafting is proposed. A heart team approach is recommended that accounts for clinical, procedural, operator, and institutional factors, and features shared decision-making that meets the needs and preferences of each patient and their specific clinical situation.

BACKGROUND Resolute Onyx polymer-based zotarolimus-eluting stents (ZES) were noninferior in safety and effectiveness to BioFreedom polymer-free biolimus A9-coated stents (DCS) in high-bleeding-risk (HBR) patients treated with 1-month dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) at 1 year. OBJECTIVES This study reports the final 2-year results of the randomized Onyx ONE trial. METHODS The Onyx ONE (A Randomized Controlled Trial With Resolute Onyx in One Month Dual Antiplatelet Therapy (DAPT) for High-Bleeding Risk Patients) trial randomly assigned HBR patients to treatment with ZES or DCS. Following 1-month DAPT, event-free patients received SAPT (either aspirin or a P2Y12 inhibitor at physician discretion). The primary safety endpoint, a composite of cardiac death, myocardial infarction, or stent thrombosis at 1 year, was determined at 1 year. Rates of primary and secondary endpoints were calculated after final follow-up at 2 years. RESULTS A total of 1,003 patients were randomly allocated to ZES and 993 patients to DCS. Follow-up was complete in 980 (97.7%) ZES patients and 962 (96.9%) DCS patients at 2 years. The primary safety endpoint occurred in 208 (21.2%) patients in the ZES group and 199 (20.7%) patients in the DCS group (risk difference: 0.5%; 95% CI: -3.1% to 4.2%; P = 0.78) at 2 years without significant differences in individual components of the composite endpoint. The secondary effectiveness endpoint occurred in 217 (22.1%) patients in the ZES group and 202 (21.0%) patients in the DCS group (risk difference: 1.1%; 95% CI: -2.5% to 4.8%; P = 0.54). CONCLUSIONS Among patients at HBR treated with 1-month DAPT followed by SAPT, the Resolute Onyx polymer-based ZES had similar 2-year outcomes for the primary safety and secondary effectiveness endpoint compared with the BioFreedom polymer-free DCS. (A Randomized Controlled Trial With Resolute Onyx in One Month Dual Antiplatelet Therapy [DAPT] for High-Bleeding Risk Patients [Onyx ONE]; NCT03344653).

Connecting the antegrade wire (AW) and the retrograde wire (RW) is a goal of chronic total occlusion (CTO) treatment, but angiographic guidewire location is sometimes misleading.The aim of this study was to evaluate the association between intravascular ultrasound (IVUS)-defined AW and RW position and procedural outcomes when treating CTO lesions using the retrograde approach.Overall, 191 CTO lesions treated using an IVUS-guided retrograde approach at three centres in Japan, China, and the USA were included.When the AW and RW angiographically overlapped, four wire positions were seen on IVUS: (i) AW within the plaque (AW-intraplaque) and RW-intraplaque in 34%; (ii) AW-intraplaque and RW in the subintimal space (RW-subintima) in 28%; (iii) AW-subintima and RW-subintima in 22%; or (iv) AW-subintima and RW-intraplaque in 16%. The procedure succeeded without repositioning the wire in 89% of AW-intraplaque/RW-intraplaque, 61% of AW-intraplaque/RW-subintima and 57% of AW-subintima/RW-subintima, but only one (3%) AW-subintima/RW-intraplaque. Lesion and procedure complexity and failure/complications were greatest in AW-subintima/RW-intraplaque.IVUS-identified vascular compartment concordance versus IVUS-identified vascular compartment mismatch leads to higher success rates irrespective of intraplaque or subintimal passage. AW-subintima/RW-intraplaque was associated with the most complex CTO morphology and procedure, and repositioning the wire was almost always necessary. Visual summary. When the antegrade wire is in the subintimal space and the retrograde wire is in the intraplaque, re-wiring is almost always necessary.

BACKGROUND: A large, prospective, multicentre trial recently showed that fractional flow reserve (FFR) derived from coronary angiography (FFR(angio)) has an accuracy of 92% compared with conventional guidewire-based FFR (FFR(wire)); however, little is known about whether specific patient/lesion characteristics affect the diagnostic performance. AIMS: The primary goal of the present study was to investigate whether specific patient or lesion characteristics such as high body mass index (BMI), presentation with an acute coronary syndrome, or lesion location affect the diagnostic performance of FFR(angio) in patients enrolled in the FAST-FFR study. METHODS: FFR(angio) was measured in a blinded fashion in 301 patients (319 vessels) who were undergoing FFR(wire) assessment. Using an FFR(wire) ≤0.80 as a reference, the diagnostic performance of FFR(angio) was compared in pre-specified subgroups. RESULTS: The mean FFR(wire) and FFR(angio) were 0.81±0.13 and 0.80±0.12. Overall, FFR(angio) had a sensitivity of 93.5% and specificity of 91.2% for predicting FFR(wire). Patient characteristics including age, sex, clinical presentation, body mass index, and diabetes did not affect sensitivity or specificity (p>0.05 for all). Similarly, lesion characteristics including calcification and tortuosity did not affect sensitivity or specificity (p>0.05 for all), nor did lesion location (proximal, middle, versus distal). Sensitivity was equally high across all target vessels, while specificity was highest in the LAD and lower (~85%) in the RCA and LCx (p

Severe acute respiratory syndrome coronavirus 2 is associated with a prothrombotic state in infected patients. After presenting a case of right ventricular thrombus in a COVID-19 patient, we discuss the unique challenges in the workup and treatment of COVID-19 patients highlighting our COVID-19 modified pulmonary embolism response team (PERT) algorithm., Graphical abstract

Objectives: The aim of this study was to investigate whether therapeutic intravascular ultrasound pulmonary artery denervation (PDN) is safe and reduces pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension (PAH) on a minimum of dual oral therapy. Background: Early studies have suggested that PDN can reduce PVR in patients with PAH. Methods: TROPHY1 (Treatment of Pulmonary Hypertension 1) was a multicenter, international, open-label trial undertaken at 8 specialist centers. Patients 18 to 75 years of age with PAH were eligible if taking dual oral or triple nonparenteral therapy and not responsive to acute vasodilator testing. Eligible patients underwent PDN (TIVUS System). The primary safety endpoint was procedure-related adverse events at 30 days. Secondary endpoints included procedure-related adverse events, disease worsening and death to 12 months, and efficacy endpoints that included change in pulmonary hemodynamic status, 6-min walk distance, and quality of life from baseline to 4 or 6 months. Patients were to remain on disease-specific medication for the duration of the study. Results: Twenty-three patients underwent PDN, with no procedure-related serious adverse events reported. The reduction in PVR at 4- or 6-month follow-up was 94 ± 151 dyn·s·cm−5 (p = 0.001) or 17.8%, which was associated with a 42 ± 63 m (p = 0.02) increase in 6-min walk distance and a 671 ± 1,555 step (p = 0.04) increase in daily activity. Conclusions: In this multicenter early feasibility study, PDN with an intravascular ultrasound catheter was performed without procedure-related adverse events and was associated with a reduction in PVR and increases in 6-min walk distance and daily activity in patients with PAH on background dual or triple therapy., SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus-coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drug-coated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P = 0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P = 0.007 for noninferiority). CONCLUSIONS Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.).

Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.

BACKGROUND AND RATIONALE Polymer-free drug-eluting stent (DES) implantation in combination with 1-month dual antiplatelet therapy (DAPT) has shown superior safety and efficacy outcomes compared with bare-metal stents among patients with high-bleeding risk (HBR) treated with 1-month DAPT. The safety and efficacy of the newer-generation durable-polymer DES Resolute Onyx compared with polymer-free DES among HBR patients treated with 1-month DAPT is unknown. TRIAL DESIGN The Onyx ONE global randomized trial is an international, prospective, randomized, blinded, controlled study enrolling HBR patients undergoing percutaneous coronary intervention. The trial will randomize up to 2,000 patients in a 1:1 fashion to receive either the durable-polymer Resolute Onyx DES or the polymer-free Biosensors BioFreedom DES. After index procedure, patients in both arms will be treated with 1 month of DAPT (aspirin and oral P2Y12 inhibitor), followed by single antiplatelet therapy thereafter. The primary end point is the composite end point of cardiac death, myocardial infarction, or stent thrombosis at 1-year follow-up. The powered secondary end point is target lesion failure (defined as the composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization) at 1 year. Patient follow-up is planned for 1, 2, and 6 months and 1 and 2 years after the procedure. CONCLUSIONS The Onyx ONE global randomized trial is the first study to directly compare the safety and efficacy of a durable polymer DES (Resolute Onyx) with a polymer-free DES (BioFreedom) in HBR patients treated with 1 month of DAPT.

Introduction: The presence of severe coronary artery calcification is associated with higher rates of angiographic complications during percutaneous coronary intervention (PCI), as well as higher major adverse cardiac events compared with non-calcified lesions. Incorporating orbital atherectomy (OAS) for effective preparation of severely calcified lesions can help maximize the benefits of PCI by attaining maximal luminal gain (or stent expansion) and improve long-term outcomes (by reducing need for revascularization). Areas covered: In this manuscript, the prevalence, risk factors, and impact of coronary artery calcification on PCI are reviewed. Based on current data and experience, the authors review orbital atherectomy technique and best practices to optimize lesion preparation. Expert Commentary: The coronary OAS is the only device approved for use in the U.S. as a treatment for de novo, severely calcified coronary lesions to facilitate stent delivery. Advantages of the device include its ease of use and a mechanism of action that treats bi-directionally, allowing for continuous blood flow during treatment, minimizing heat damage, slow flow, and subsequent need for revascularization. The OAS technique tips reviewed in this article will help inform interventional cardiologists treating patients with severely calcified lesions.

The Medical Device Epidemiological Network Initiative (MDEpiNet) is a public-private partnership between the US Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) and participating partners. The Predictable and SuStainable Implementation of National Cardiovascular Registries (PASSION) program is an MDEpiNet-sponsored program which aims to demonstrate the goals of MDEpiNet by using cardiovascular medical device registries to bridge evidence gaps across the medical device total product life cycle (TPLC). To this end, a PASSION Think Tank meeting took place in October 2014 in Silver Spring, MD, to facilitate discussion between stakeholders about the successes, challenges, and future novel applications of medical device registries, with particular emphasis on identifying pilot projects. Participants spanned a broad range of groups including patients, device manufacturers, regulators, physicians/academicians, professional societies, providers, and payers. The meeting focus included four areas of cardiovascular medicine intended to cultivate interest in four MDEpiNet Disease Specific/Device Specific Working Groups: coronary intervention, electrophysiology, valvular disease, and peripheral vascular disease. In addition, more general issues applying to registry-based infrastructure and analytical methodologies for assessing device benefit/risk were considered to provide context for the Working Groups as PASSION programs going forward. This article summarizes the discussions at the meeting and the future directions of the PASSION program.

The goal of this study was to determine whether a less-invasive approach to aortic valve replacement (AVR) improves clinical outcomes in diabetic patients with aortic stenosis (AS).Diabetes is associated with increased morbidity and mortality after surgical AVR for AS.Among treated patients with severe symptomatic AS at high risk for surgery in the PARTNER (Placement of Aortic Transcatheter Valve) trial, we examined outcomes stratified according to diabetes status of patients randomly assigned to receive transcatheter or surgical AVR. The primary outcome was all-cause mortality at 1 year.Among 657 patients enrolled in PARTNER who underwent treatment, there were 275 patients with diabetes (145 transcatheter, 130 surgical). There was a significant interaction between diabetes and treatment group for 1-year all-cause mortality (p = 0.048). Among diabetic patients, all-cause mortality at 1 year was 18.0% in the transcatheter group and 27.4% in the surgical group (hazard ratio: 0.60 [95% confidence interval: 0.36 to 0.99]; p = 0.04). Results were consistent among patients treated via transfemoral or transapical routes. In contrast, among nondiabetic patients, there was no significant difference in all-cause mortality at 1 year (p = 0.48). Among diabetic patients, the 1-year rates of stroke were similar between treatment groups (3.5% transcatheter vs. 3.5% surgery; p = 0.88), but the rate of renal failure requiring dialysis30 days was lower in the transcatheter group (0% vs. 6.1%; p = 0.003).Among patients with diabetes and severe symptomatic AS at high risk for surgery, this post-hoc stratified analysis of the PARTNER trial suggests there is a survival benefit, no increase in stroke, and less renal failure from treatment with transcatheter AVR compared with surgical AVR. (The PARTNER Trial: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).

The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI) clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection.A recent study confirmed that VARC definitions have already been incorporated into clinical and research practice and represent a new standard for consistency in reporting clinical outcomes of patients with symptomatic severe aortic stenosis (AS) undergoing TAVI. However, as the clinical experience with this technology has matured and expanded, certain definitions have become unsuitable or ambiguous.Two in-person meetings (held in September 2011 in Washington, DC, USA, and in February 2012 in Rotterdam, Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and non-interventional cardiologists, imaging specialists, neurologists, geriatric specialists, and clinical trialists), the US Food and Drug Administration (FDA), and industry representatives, provided much of the substantive discussion from which this VARC-2 consensus manuscript was derived. This document provides an overview of risk assessment and patient stratification that need to be considered for accurate patient inclusion in studies. Working groups were assigned to define the following clinical endpoints: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and a miscellaneous category including relevant complications not previously categorized. Furthermore, comprehensive echocardiographic recommendations are provided for the evaluation of prosthetic valve (dys)function. Definitions for the quality of life assessments are also reported. These endpoints formed the basis for several recommended composite endpoints.This VARC-2 document has provided further standardization of endpoint definitions for studies evaluating the use of TAVI, which will lead to improved comparability and interpretability of the study results, supplying an increasingly growing body of evidence with respect to TAVI and/or surgical aortic valve replacement. This initiative and document can furthermore be used as a model during current endeavours of applying definitions to other transcatheter valve therapies (for example, mitral valve repair).

ObjectivesThis study sought to perform a weighted meta-analysis to determine the rates of major outcomes after transcatheter aortic valve replacement (TAVR) using Valve Academic Research Consortium (VARC) definitions and to evaluate their current use in the literature.BackgroundRecently, the published VARC definitions have helped to add uniformity to reporting outcomes after TAVR.MethodsA comprehensive search of multiple electronic databases from January 1, 2011, through October 12, 2011, was conducted using predefined criteria. We included studies reporting at least 1 outcome using VARC definitions.ResultsA total of 16 studies including 3,519 patients met inclusion criteria and were included in the analysis. The pooled estimate rates of outcomes were determined according to VARC's definitions: device success, 92.1% (95% confidence interval [CI]: 88.7% to 95.5%); all-cause 30-day mortality, 7.8% (95% CI: 5.5% to 11.1%); myocardial infarction, 1.1% (95% CI: 0.2% to 2.0%); acute kidney injury stage II/III, 7.5% (95% CI: 5.1% to 11.4%); life-threatening bleeding, 15.6% (95% CI: 11.7% to 20.7%); major vascular complications, 11.9% (95% CI: 8.6% to 16.4%); major stroke, 3.2% (95% CI: 2.1% to 4.8%); and new permanent pacemaker implantation, 13.9% (95% CI: 10.6% to 18.9%). Medtronic CoreValve prosthesis use was associated with a significant higher rate of new permanent pacemaker implantation compared with the Edwards prosthesis (28.9% [95% CI: 23.0% to 36.0%] vs. 4.9% [95% CI: 3.9% to 6.2%], p < 0.0001). The 30-day safety composite endpoint rate was 32.7% (95% CI: 27.5% to 38.8%) and the 1-year total mortality rate was 22.1% (95% CI: 17.9% to 26.9%).ConclusionsVARC definitions have already been used by the TAVR clinical research community, establishing a new standard for reporting clinical outcomes. Future revisions of the VARC definitions are needed based on evolving TAVR clinical experiences.

BACKGROUND: Treatment with the direct thrombin inhibitor bivalirudin, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, results in similar suppression of ischemia while reducing hemorrhagic complications in patients with stable angina and non-ST-segment elevation acute coronary syndromes who are undergoing percutaneous coronary intervention (PCI). The safety and efficacy of bivalirudin in high-risk patients are unknown. METHODS: We randomly assigned 3602 patients with ST-segment elevation myocardial infarction who presented within 12 hours after the onset of symptoms and who were undergoing primary PCI to treatment with heparin plus a glycoprotein IIb/IIIa inhibitor or to treatment with bivalirudin alone. The two primary end points of the study were major bleeding and combined adverse clinical events, defined as the combination of major bleeding or major adverse cardiovascular events, including death, reinfarction, target-vessel revascularization for ischemia, and stroke (hereinafter referred to as net adverse clinical events) within 30 days. RESULTS: Anticoagulation with bivalirudin alone, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, resulted in a reduced 30-day rate of net adverse clinical events (9.2% vs. 12.1%; relative risk, 0.76; 95% confidence interval [CI] 0.63 to 0.92; P=0.005), owing to a lower rate of major bleeding (4.9% vs. 8.3%; relative risk, 0.60; 95% CI, 0.46 to 0.77; P

ObjectivesThe aim of this study was to examine outcomes related to the use of the Endeavor zotarolimus-eluting stent (ZES) (Medtronic CardioVascular, Santa Rosa, California) compared with the TAXUS paclitaxel-eluting stent (PES) (Boston Scientific Corp., Natick, Massachusetts) in the 477 patients with diabetes mellitus (DM) enrolled in the randomized ENDEAVOR IV (Randomized Comparison of Zotarolimus- and Paclitaxel-Eluting Stents in Patients with Coronary Artery Disease) trial.BackgroundPercutaneous coronary intervention (PCI) in diabetic patients is associated with increased rates of restenosis-related end points compared with PCI in nondiabetic patients. Although ZES has been associated with similar clinical efficacy compared with PES in the overall trial population of the ENDEAVOR IV trial, whether these results are maintained in the higher-risk restenosis subgroup of patients with DM has not been determined.MethodsClinical and angiographic outcomes were compared according to randomized treatment assignment to either ZES or PES.ResultsBaseline characteristics were similar among ZES (n = 241) and PES (n = 236) diabetic patients, with slightly longer lesion lengths in PES-treated patients (12.9 mm vs. 14.0 mm, p = 0.041). Among the 86 DM patients assigned to routine angiographic follow-up (18% of the overall DM cohort), in-stent percent diameter stenosis at 8 months was greater among ZES-treated patients (32.9 vs. 21.1, p = 0.023), with a trend toward higher in-stent late loss. One-year clinical outcomes were similar among DM patients treated with either ZES or PES (target vessel failure: 8.6% vs. 10.8%, p = 0.53; target lesion revascularization: 6.9% vs. 5.8%, p = 0.70; target vessel revascularization: 8.6% vs. 9.4%, p = 0.87). There were no significant interactions between DM status and stent type with respect to the outcomes measured, and the relative efficacy/safety of ZES and PES were similar among insulin- and noninsulin-requiring subgroups.ConclusionsOne-year clinical outcomes were similar among DM patients treated with ZES and PES in the ENDEAVOR IV trial. These findings parallel the overall trial results, which demonstrated similar efficacy and safety of ZES and PES for single de novo coronary lesions.

ObjectivesWe sought to examine the safety and efficacy of paclitaxel-eluting stents (PES) in patients with diabetes mellitus (DM).BackgroundCompared with patients without DM, patients with DM undergoing percutaneous coronary intervention are at increased risk for mortality and restenosis. The safety of drug-eluting stents in diabetic patients has recently been called into question by a published meta-analysis of randomized trials.MethodsPatient-level data were pooled from 5 prospective, double-blind, randomized trials of PES versus bare-metal stents (BMS) (n = 3,513). Safety and efficacy outcomes through 4 years of follow-up were assessed among the 827 randomized patients (23.6%) with DM.ResultsPatients treated with PES and BMS has similar baseline characteristics among both the diabetic and nondiabetic cohorts within these trials. At 4-year follow-up, there were no significant differences between PES and BMS among diabetic patients in the rates of death (8.4% vs. 10.3%, respectively, p = 0.61), myocardial infarction (6.9% vs. 8.9%, p = 0.17), or stent thrombosis (1.4% vs. 1.2%, p = 0.92). Treatment of diabetic patients with PES compared with treatment with BMS was associated with a significant and durable reduction in target lesion revascularization over the 4-year follow-up period (12.4% vs. 24.7%, p < 0.0001). The relative safety and efficacy of PES compared with the relative safety and efficacy of BMS in diabetic patients extended to both those requiring and not requiring insulin.ConclusionsIn these 5 randomized trials in which patients with single, primarily noncomplex lesions were enrolled, treatment with PES compared with treatment with BMS was safe and effective, resulting in markedly lower rates of target lesion revascularization at 4 years, with similar rates of death, myocardial infarction, and stent thrombosis.

ObjectivesWe aimed to identify correlates of Thrombolysis In Mycocardial Infarction (TIMI) major/minor bleeding among eptifibatide-treated patients undergoing percutaneous coronary intervention (PCI).BackgroundEvaluation of bleeding predictors among patients treated with glycoprotein IIb/IIIa receptor inhibition might aid in the identification of targets to reduce bleeding risk.MethodsData were analyzed from 567 moderate- to high-risk PCI patients with non–ST-segment elevation acute coronary syndrome (NSTEACS) treated with eptifibatide/reduced-dose unfractionated heparin or eptifibatide/reduced-dose enoxaparin enrolled in the Randomized Trial to Evaluate the Relative Protection Against Post-PCI Microvascular Dysfunction and Post-PCI Ischemia Among Anti-Platelet and Anti-Thrombotic Agents–Thrombolysis In Myocardial Infarction-30 (PROTECT–TIMI-30).ResultsThe incidence of significant bleeding was 3.2% with a median time to event of 7.0 h after the first eptifibatide bolus. Increased age was the only independent correlate of bleeding events. Among patients with reduced creatinine clearance (CrCl), lack of adjustment of the maintenance infusion for CrCl ≤50 ml/min occurred frequently (15 of 33 patients, or 45%) and was associated with a high rate of bleeding (20%). The association of CrCl with bleeding appeared to be largely mediated by the incorporation of age in the estimation of CrCl. Patient gender, Cr, weight, and the peak activated clotting time were not associated with bleeding.ConclusionsAmong NSTEACS PCI patients treated with eptifibatide, increased age was a significant correlate of bleeding events and appeared to explain the association between low CrCl and bleeding. The more widespread use of CrCl or other estimates of renal function over Cr may lead to more appropriate dose adjustments of eptifibatide.

ObjectivesThe purpose of this study was to assess the prognostic impact of intraprocedural thrombotic events (IPTE) during percutaneous coronary intervention (PCI).BackgroundIschemic complications of PCI are infrequent but prognostically important. How often these events are a consequence of intraprocedural complications is unknown, with only limited data assessing the occurrence and importance of IPTE.MethodsA total of 3,428 patients who underwent PCI for non–ST-segment elevation acute coronary syndrome in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial underwent detailed frame-by-frame core laboratory angiographic analysis. An IPTE, defined as the development of new or increasing thrombus, abrupt vessel closure, no reflow, slow reflow, or distal embolization at any time during the procedure, occurred in 121 patients (3.5%).ResultsPatients with IPTE had higher in-hospital, 30-day, and 1-year major adverse cardiac event rates than patients without IPTE (25.6% vs. 6.3% in-hospital, 30.6% vs. 9.3% at 30 days, and 37.0% vs. 20.5% at 1 year; p < 0.0001 for each). An IPTE was strongly associated with Q-wave myocardial infarction and out-of-laboratory definite/probable stent thrombosis (in-hospital 3.3% vs. 0.5%, p = 0.006; 30 days 5.8% vs. 1.3%, p < 0.0001; and 1 year 6.7% vs. 2.0%, p = 0.0002). Unplanned revascularization, target vessel revascularization, and major bleeding not associated with coronary artery bypass graft surgery were also increased among patients with IPTE, as was overall 30-day mortality (3.3% vs. 0.7%, p = 0.002). Moreover, IPTE was an independent predictor of 30-day and 1-year composite death/myocardial infarction, stent thrombosis, and major adverse cardiac events.ConclusionsAlthough infrequent among patients undergoing early PCI for moderate and high-risk non–ST-segment elevation acute coronary syndrome, IPTE was strongly associated with subsequent adverse outcomes including death, myocardial infarction, and stent thrombosis.

ObjectivesThis study sought to evaluate the long-term safety and efficacy of everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) in patients with obstructive coronary artery disease.BackgroundThe use of EES compared to PES has been shown to result in improved clinical outcomes in patients undergoing PCI. However, there have been concerns regarding the durability of these benefits over longer-term follow-up.MethodsSPIRIT III was a prospective, multicenter trial in which 1,002 patients were randomized 2:1 to EES versus PES. Endpoints included ischemia-driven target vessel failure (TVF) (death, myocardial infarction (MI), or ischemia-driven target vessel revascularization [TVR]), the pre-specified primary endpoint), target lesion failure (TLF) (cardiac death, target-vessel MI, or ischemia-driven target lesion revascularization [TLR]), major adverse cardiac events (MACE) (cardiac death, MI, or ischemia-driven TLR), their individual components and stent thrombosis.ResultsFive-year follow-up was available in 91.9% of patients. Treatment with EES versus PES resulted in lower 5-year Kaplan-Meier rates of TVF (19.3% vs. 24.5%, p = 0.05), TLF (12.7% vs. 19.0%, p = 0.008), and MACE (13.2% vs. 20.7%, p = 0.007). EES also resulted in reduced rates of all-cause death (5.9% vs. 10.1%, p = 0.02), with nonsignificantly different rates of MI, stent thrombosis, and TLR, and no evidence of late catch-up of TLR over time.ConclusionsAt 5 years after treatment, EES compared to PES resulted in durable benefits in composite safety and efficacy measures as well as all-cause mortality. Additionally, the absolute difference in TLR between devices remained stable over time without deterioration of effect during late follow-up.

ObjectivesThis study sought to determine the frequency and impact of coronary calcification among patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS).BackgroundSmall studies in patients with stable coronary artery disease have suggested a worse prognosis after PCI of calcified compared with noncalcified lesions. Little is known about the impact of coronary calcification on outcomes after PCI for patients presenting with non–ST-segment elevation and ST-segment elevation ACS.MethodsData from 6,855 patients presenting with ACS in whom PCI was performed were pooled from 2 large-scale randomized, controlled trials, ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction). One-year outcomes were analyzed according to the severity of PCI target lesion calcification (none/mild, moderate, or severe) as assessed by an independent angiographic core laboratory.ResultsTarget lesion calcification was severe in 402 patients (5.9%), moderate in 1,788 (26.1%), and none/mild in 4,665 (68.1%). Moderate/severe target lesion calcification was more frequent in older patients, men, hypertensive patients, and those presenting with ST-segment elevation myocardial infarction (STEMI). The unadjusted 1-year rates of death, cardiac death, definite stent thrombosis, and ischemic target lesion revascularization (TLR) and target vessel revascularization were significantly increased in patients with moderate/severe target lesion calcification. By multivariable analysis, the presence of moderate/severe target lesion calcification was an independent predictor of 1-year definite stent thrombosis (hazard ratio [HR]: 1.62; 95% confidence interval [CI]: 1.14 to 2.30; p = 0.007) and ischemic TLR (HR: 1.44; 95% CI: 1.17 to 1.78; p = 0.0007).ConclusionsModerate/severe lesion calcification was relatively frequent in patients with non–ST-segment elevation ACS and STEMI and was strongly predictive of stent thrombosis and ischemic TLR at 1 year. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158; Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966)

Stroke is a potential complication of treating patients with aortic stenosis via surgical aortic valve replacement (AVR), transcatheter aortic valve replacement (TAVR), and balloon aortic valvuloplasty. Because there are limited and heterogeneous data on the incidence, risk factors, and outcomes of stroke among patients being treated for aortic stenosis, we performed a comprehensive review of the literature. The risk of stroke after AVR in the general population is approximately 1.5%, and the risk is increased (to approximately 2% to 4%) in older and higher-risk patients. Strokes were reported in 1.5% to 6% of patients treated with TAVR, and in the only randomized trial of AVR versus TAVR, there was an increased risk of 30-day strokes (minor and major strokes and transient ischemic attacks) with TAVR (5.5% vs. 2.4%, p = 0.04).

ObjectivesFive-year clinical follow-up has been scheduled per protocol by the 4 Cypher (Cordis/Johnson & Johnson, Warren, New Jersey) sirolimus-eluting stent (SES) versus bare-metal stent (BMS) randomized trials.BackgroundA delayed arterial healing response after drug-eluting stent implantation has raised concerns about the long-term safety of drug-eluting stents.MethodsIn a pooled analysis of 4 randomized trials, 1,748 patients were assigned to receive either an SES (n = 878) or BMS (n = 870).ResultsAt 5 years, there was no significant difference in the rate of death, myocardial infarction (MI), or the composite of death/MI between the 2 groups (15.1% in the SES group vs. 13.6% in the BMS group; p = 0.36). The 5-year incidence of stent thrombosis by the Academic Research Consortium definition did not differ between SES and BMS (definite/probable stent thrombosis, 2.1% vs. 2.0%; p = 0.99). The incidence of very late stent thrombosis was also similar between the SES and BMS groups (1.4% vs. 0.7%; p = 0.22). The annualized rates of definite/probable stent thrombosis after 1 year were 0.4% for SES and 0.2% for BMS. The 5-year incidence of target vessel revascularization was significantly lower in the SES group (15.2% vs. 30.1%; p < 0.0001).ConclusionsIn this patient-level pooled analysis, overall use of SES compared with BMS demonstrated persistent superior efficacy at 5 years in terms of a reduction in target vessel revascularization, without an increase in rates of death, MI, or stent thrombosis. (The Initial Double-Blind Drug-Eluting Stent vs Bare-Metal Stent Study, NCT00233805; The Study of the BX Velocity Stent in the Treatment of De Novo Artery Lesions, NCT00381420; Study of Sirolimus-Coated BX VELOCITY Balloon-Expandable Stent in Treatment of de Novo Native Coronary Artery Lesions [SIRIUS], NCT00232765; The Study of the BX VELOCITY Stent In Patients With De Novo Coronary Artery Lesions, NCT00235144)

ObjectivesThe aim of this study was to identify clinical, procedural, and angiographic correlates of late/very late drug-eluting stent (DES) thrombosis as well as to determine the clinical outcomes of these events.BackgroundLate/very late DES thromboses are a poorly studied phenomenon, partly due to the relative infrequency of these events, even in large cohort studies.MethodsIn the DESERT (International Drug-Eluting Stent Event Registry of Thrombosis), a retrospective, case-control registry, 492 cases of late/very late definite DES thrombosis from 21 international sites were matched in a 1:1 fashion with controls without stent thrombosis (ST). Controls were matched according to 2 criteria: same enrolling institution and date of initial DES implantation. Baseline and procedural variables were collected, and clinical follow-up was obtained for patients with ST as long as 1 year after the event. Offline quantitative coronary angiography was performed for a subset of 378 case-control pairs.ResultsThe majority of ST events occurred after 1 year (75%) and continued to occur for as long as 7.3 years. The clinical presentation of late/very late ST events was mainly myocardial infarction (66.7% ST-segment elevation myocardial infarction and 22.0% non–ST-segment elevation myocardial infarction); in-hospital mortality was 3.8%. A minority of patients (30%) with ST were receiving dual-antiplatelet therapy at the time of the event. Independent clinical correlates of late/very late ST were younger age, African-American race, current smoking, multivessel disease, longer stented length, overlapping stents, and percutaneous coronary intervention of vein graft lesions. Independent angiographic correlates for late/very late ST were lesions within the left anterior descending artery or a bypass graft, thrombus, and a larger residual diameter stenosis after the initial DES implantation. Despite the large sample of ST cases, all identified correlates of late/very late ST had weak associations with subsequent ST (all odds ratios

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.

ObjectivesThis study sought to identify the incidence, predictors, and prognostic impact of bleeding complications (BC) after surgical aortic valve replacement (SAVR) compared with transcatheter aortic valve replacement (TAVR).BackgroundBleeding complications after SAVR and TAVR are frequent and may be associated with an unfavorable prognosis.MethodsIn the randomized controlled PARTNER (Placement of Aortic Transcatheter Valve) I trial, 657 patients from cohort A (operable high risk) were randomly assigned to SAVR or TAVR (transfemoral [TF] if iliofemoral access was suitable or transapical [TA] if not) and received the designated treatment. First-generation Edwards SAPIEN valves and delivery systems (Edwards Lifesciences, Irvine, California) were used for TAVR, through a 22- or 24-F sheath. The 30-day rates of major BC (modified Valve Academic Research Consortium definitions), predictors of BC, and their association with 1-year mortality were assessed.ResultsA total of 71 (22.7%), 27 (11.3%), and 9 (8.8%) patients had major BC within 30 days of the procedure after SAVR, TF-TAVR, and TA-TAVR, respectively (p < 0.0001). SAVR was associated with a significantly higher 30-day rate of transfusion (17.9%) than either TF-TAVR (7.1%) or TA-TAVR (4.8%; p < 0.0001). Independent predictors of major BC were the occurrence of major vascular complications and use of intraprocedural hemodynamic support among TF-TAVR patients, severe procedural complications requiring conversion to open surgery among TA-TAVR patients, and the presence of low hemoglobin at baseline among SAVR patients. Major BC was identified as the strongest independent predictor of 1-year mortality among the full cohort. However, risk-adjusted analyses demonstrated a significant interaction between BC and treatment strategy with respect to mortality, suggesting that BC after SAVR have a greater impact on prognosis than after TAVR.ConclusionsAmong high-risk aortic stenosis patients enrolled in the PARTNER I randomized trial, BC were more common after SAVR than after TAVR and were also associated with a worse long-term prognosis. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894)

ObjectivesThis study sought to examine sex-specific differences in outcomes after surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) in high-risk patients with severe aortic stenosis.BackgroundThe PARTNER (Placement of Aortic Transcatheter Valve) trial demonstrated similar 2-year survival with SAVR or TAVR for high-risk patients, but sex-specific outcomes are unknown.MethodsIn all, 699 patients (300 female) were randomly assigned 1:1 to either SAVR or TAVR with a balloon expandable pericardial tissue valve. Baseline characteristics and 2-year outcomes of TAVR versus SAVR were compared among males and females.ResultsBaseline characteristics differed between the sexes. Despite higher Society of Thoracic Surgeons mortality risk scores (11.9 vs. 11.6; p = 0.05), female patients had lower prevalence of coronary artery disease (64.4% vs. 83.7%), prior coronary artery bypass graft surgery (19.8% vs. 61.2%), peripheral vascular disease (36.4% vs. 46.9%), diabetes mellitus (35.6% vs. 45.6%), and elevated creatinine (11.7% vs. 23.9%). Among female patients, procedural mortality trended lower with TAVR versus SAVR (6.8% vs. 13.1%; p = 0.07) and was maintained throughout follow-up (hazard ratio [HR]: 0.67; 95% confidence interval [CI]: 0.44 to 1.00; p = 0.049), driven by the transfemoral arm (HR: 0.55; 95% CI: 0.32 to 0.93; p = 0.02). Among male patients, although procedural mortality was lower with TAVR (6% vs. 12.1%; p = 0.03), there was no overall survival benefit (HR: 1.15; 95% CI: 0.82 to 1.61; p = 0.42).ConclusionsIn this retrospective subanalysis of high-risk, symptomatic aortic stenosis patients in the PARTNER trial, female subjects had lower late mortality with TAVR versus SAVR. This was especially true among patients suitable for transfemoral access and suggests that TAVR may be preferred over surgery for high-risk female patients. A randomized, controlled trial conducted specifically in female patients is necessary to properly study differences in mortality between treatment modalities. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894)

ObjectivesIn this substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial, we investigated the relationship between chronic kidney disease (CKD) and clinical outcomes, and compared the safety and efficacy of bivalirudin monotherapy versus heparin plus a glycoprotein IIb/IIIa inhibitor (GPI).BackgroundCKD is an important predictor of prognosis in the general population. The outcomes of patients with CKD and acute coronary syndromes (ACS) have not been well studied.MethodsIn the ACUITY study, 13,819 patients with moderate- and high-risk ACS undergoing an early, invasive strategy were randomly assigned to 1 of 3 antithrombin regimens: a heparin plus a GPI, bivalirudin plus a GPI, or bivalirudin monotherapy. CKD (creatinine clearance

ObjectivesWe sought to identify correlates of 30-day adverse events among patients undergoing percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG).BackgroundAlthough the use of distal embolic protection devices during SVG intervention reduces major adverse cardiac events (MACE), many patients still experience MACE despite distal embolic protection, and the major predictors of MACE among these patients are not well-characterized.MethodsCorrelates of 30-day MACE and peri-procedural creatine kinase-myocardial band (CK-MB) elevation were assessed among 631 patients undergoing SVG intervention with distal embolic protection enrolled in the PRIDE (PRotection during saphenous vein graft Intervention to prevent Distal Embolization) study, a randomized comparison of the TriActiv System (Kensey-Nash Corp., Exton, Pennsylvania) with an active control group (Guardwire [Medtronic, Santa Clara, California] or Filterwire [Boston Scientific, Minneapolis, Minnesota]).ResultsBaseline covariates associated with MACE were longer lesion length, greater angiographically assessed estimated plaque volume, and higher SVG degeneration score. Graft age and angina class were not associated with adverse events. Angiographic lesion length was significantly correlated with more complex angiographic metrics such as estimated plaque volume and the SVG degeneration score. In multivariable analyses, angiographic lesion length was the strongest independent correlate of MACE (odds ratio [OR] 2.81 [95% confidence interval (CI) 1.82 to 4.34]/log-increase in lesion length, p < 0.001) with a graded increase in MACE observed with increasing lesion lengths. Similarly, the strongest independent correlate of CK-MB elevation was lesion length (OR 2.54 [95% CI 1.59 to 4.04]/log-increase in lesion length, p < 0.001). The associations between lesion length and both MACE and CK-MB elevation were consistent among the studied embolic protection devices (TriActiv, Guardwire, or Filterwire).ConclusionsAngiographic lesion length was the strongest correlate of short-term adverse events among patients undergoing SVG intervention with distal embolic protection, with incremental effects noted at even relatively short lesion lengths.

ObjectivesThe purpose of this study was to establish a scoring system to evaluate the risk of side branch (SB) occlusion in patients undergoing coronary bifurcation intervention.BackgroundThe risk of SB occlusion is the most important consideration affecting the selection of an optimal intervention strategy.MethodsA total of 1,545 consecutive patients undergoing percutaneous coronary intervention for bifurcation lesions (1,601 lesions treated with a single stent technique or main vessel [MV] stenting first strategy) were studied. A total of 1,200 lesions were used to construct the risk model and score system, and 401 lesions were used to validate the model. A multivariable risk score (RESOLVE [Risk prEdiction of Side branch OccLusion in coronary bifurcation interVEntion]) was constructed with incremental weights attributed to each component variable according to its estimated coefficients. SB occlusion after MV stenting was defined as any decrease in Thrombolysis in Myocardial Infarction flow grade or absence of flow in SB after MV stenting.ResultsSB occlusion occurred in 118 (7.37%) of 1,601 bifurcation lesions. In multivariable analyses, 6 variables were independently associated with the risk of SB occlusion (model C-statistic = 0.80 [95% confidence interval: 0.75 to 0.85] with good calibration). For the 401 lesions included in the validation cohort, the RESOLVE score had a C-statistic of 0.77 (95% confidence interval: 0.69 to 0.86), with good calibration. SB occlusion rates in the validation cohort increased significantly across different risk groups, from 0.0% in the low-risk group, to 3.8% in the intermediate-risk group, and to 19.8% in the high-risk group (p < 0.001).ConclusionsThe RESOLVE score, a novel angiographic risk stratification tool, can help identify patients at risk for SB occlusion during bifurcation intervention.

ObjectivesThe aim of this study was to assess, after 2 years of follow-up, the safety, efficacy, and cost-effectiveness of a zotarolimus-eluting stent (ZES) compared with a paclitaxel-eluting stent (PES) in patients with native coronary lesions.BackgroundEarly drug-eluting stents were associated with a small but significant incidence of very late stent thrombosis (VLST), occurring >1 year after the index procedure. The ZES has shown encouraging results in clinical trials.MethodsThe ENDEAVOR IV trial (Randomized, Controlled Trial of the Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System Versus the Taxus Paclitaxel-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions), a randomized (1:1), single-blind, controlled trial (n = 1,548) compared ZES versus PES in patients with single de novo coronary lesions. Two-year follow-up was obtained in 96.0% of ZES and 95.4% of PES patients. The primary end point was target vessel failure (TVF), and safety end points included Academic Research Consortium-defined stent thrombosis. Economic end points analyzed included quality-adjusted survival, medical costs, and relative cost-effectiveness of ZES and PES.ResultsThe TVF at 2 years was similar in ZES and PES patients (11.1% vs. 13.1%, p = 0.232). There were fewer myocardial infarctions (MIs) in ZES patients (p = 0.022), due to fewer periprocedural non–Q-wave MIs and fewer late MIs between 1 and 2 years. Late MIs were associated with increased VLST (PES: 6 vs. ZES: 1; p = 0.069). Target lesion revascularization was similar comparing ZES with PES (5.9% vs. 4.6%; p = 0.295), especially in patients without planned angiographic follow-up (5.2% vs. 4.9%; p = 0.896). The cost-effectiveness of ZES and PES was similar.ConclusionsAfter 2 years of follow-up, ZES demonstrated efficacy and cost-effectiveness comparable to PES, with fewer MIs and a trend toward less VLST. (The ENDEAVOR IV Clinical Trial: A Trial of a Coronary Stent System in Coronary Artery Lesions; NCT00217269)

ObjectivesWe assessed the incidence, predictors, and outcomes of gastrointestinal bleeding (GIB) in patients with acute coronary syndromes (ACS).BackgroundGIB is a potential hemorrhagic complication in patients with ACS treated with antithrombotic and/or antiplatelet medications. The clinical outcomes associated with GIB in this setting have not been systematically studied.MethodsIn the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, 13,819 patients with moderate- and high-risk ACS, enrolled at 450 centers in 17 countries between August 2003 and December 2005, were randomized to the open-label use of 1 of 3 antithrombin regimens (heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin monotherapy).ResultsGIB within 30 days occurred in 178 patients (1.3%). Older age, baseline anemia, longer duration of study drug administration before angiogram, smoking, ST-segment deviation ≥1 mm, and diabetes were identified as independent predictors of GIB. On multivariable analysis, GIB was strongly associated with 30-day all-cause mortality (hazard ratio [HR]: 4.87 [interquartile range (IQR) 2.61 to 9.08], p < 0.0001), cardiac mortality (HR: 5.35 [IQR 2.71 to 10.59], p < 0.0001), and composite ischemia (HR: 1.94 [IQR 1.14 to 3.30], p = 0.014), as well as with 1-year all-cause mortality (HR: 3.97 [IQR 2.64 to 5.99], p < 0.0001), cardiac mortality (HR: 3.77 [IQR 2.14 to 6.63], p < 0.0001), myocardial infarction (HR: 1.74 [IQR 1.01 to 3.02], p = 0.047), and composite ischemia (HR: 1.90 [IQR 1.37 to 2.64], p = 0.0001). Patients who experienced GIB had significantly higher rates of stent thrombosis compared with patients without GIB (5.8% vs. 2.4%, p = 0.009).ConclusionsGIB is a serious condition in the scenario of ACS and is independently associated with mortality and ischemic complications.

ObjectivesThe aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI) clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection.BackgroundA recent study confirmed that VARC definitions have already been incorporated into clinical and research practice and represent a new standard for consistency in reporting clinical outcomes of patients with symptomatic severe aortic stenosis (AS) undergoing TAVI. However, as the clinical experience with this technology has matured and expanded, certain definitions have become unsuitable or ambiguous.Methods and ResultsTwo in-person meetings (held in September 2011 in Washington, DC, USA, and in February 2012 in Rotterdam, the Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and non-interventional cardiologists, imaging specialists, neurologists, geriatric specialists, and clinical trialists), the US Food and Drug Administration (FDA), and industry representatives, provided much of the substantive discussion from which this VARC-2 consensus manuscript was derived. This document provides an overview of risk assessment and patient stratification that need to be considered for accurate patient inclusion in studies. Working groups were assigned to define the following clinical endpoints: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and a miscellaneous category including relevant complications not previously categorized. Furthermore, comprehensive echocardiography recommendations are provided for the evaluation of prosthetic valve (dys)function. Definitions for the quality of life assessments are also reported. These endpoints formed the basis for several recommended composite endpoints.ConclusionsThis VARC-2 document has provided further standardization of endpoint definitions for studies evaluating the use of TAVI, which will lead to improved comparability and interpretability of the study results, supplying an increasingly growing body of evidence with respect to TAVI and/or surgical aortic valve replacement. This initiative and document can furthermore be used as a model during current endeavors of applying definitions to other transcatheter valve therapies (for example, mitral valve repair).

ObjectivesThe goal of this study was to determine whether a less-invasive approach to aortic valve replacement (AVR) improves clinical outcomes in diabetic patients with aortic stenosis (AS).BackgroundDiabetes is associated with increased morbidity and mortality after surgical AVR for AS.MethodsAmong treated patients with severe symptomatic AS at high risk for surgery in the PARTNER (Placement of Aortic Transcatheter Valve) trial, we examined outcomes stratified according to diabetes status of patients randomly assigned to receive transcatheter or surgical AVR. The primary outcome was all-cause mortality at 1 year.ResultsAmong 657 patients enrolled in PARTNER who underwent treatment, there were 275 patients with diabetes (145 transcatheter, 130 surgical). There was a significant interaction between diabetes and treatment group for 1-year all-cause mortality (p = 0.048). Among diabetic patients, all-cause mortality at 1 year was 18.0% in the transcatheter group and 27.4% in the surgical group (hazard ratio: 0.60 [95% confidence interval: 0.36 to 0.99]; p = 0.04). Results were consistent among patients treated via transfemoral or transapical routes. In contrast, among nondiabetic patients, there was no significant difference in all-cause mortality at 1 year (p = 0.48). Among diabetic patients, the 1-year rates of stroke were similar between treatment groups (3.5% transcatheter vs. 3.5% surgery; p = 0.88), but the rate of renal failure requiring dialysis >30 days was lower in the transcatheter group (0% vs. 6.1%; p = 0.003).ConclusionsAmong patients with diabetes and severe symptomatic AS at high risk for surgery, this post-hoc stratified analysis of the PARTNER trial suggests there is a survival benefit, no increase in stroke, and less renal failure from treatment with transcatheter AVR compared with surgical AVR. (The PARTNER Trial: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894)