Arie Steinvil

Overview of the 2016 U.S. Food and Drug Administration Circulatory System Devices Advisory Panel Meeting on the Absorb Bioresorbable Vascular Scaffold System

OBJECTIVES This study aims to describe the discussions and recommendations made during the U.S. Food and Drug Administration (FDA) Circulatory System Device Panel pre-market approval application for the Absorb Bioresorbable Vascular Scaffold (BVS) System. BACKGROUND The Absorb BVS System is a first-of-its-kind fully bioresorbable percutaneous coronary intervention technology. The absorb BVS was studied in the ABSORB III (A Clinical Evaluation of Absorb BVS, the Everolimus Eluting Bioresorbable Vascular Scaffold in the Treatment of Subjects with de Novo Native Coronary Artery Lesions) trial, the pivotal U.S. investigational device exemption trial. METHODS Observational report of the FDA Circulatory System Device Panel pre-market approval application meeting held on March 15, 2016. RESULTS The U.S. FDA Circulatory System Device Panel members reviewed the ABSROB III trial outcomes and additional post hoc analyses presented by the sponsor and the FDA. The ABSORB III trial met the primary endpoint of noninferiority of Absorb BVS compared with the control, XIENCE drug-eluting stent, for target lesion failure at 1 year. Although a higher numerical trend for adverse outcomes was reported for the Absorb BVS, there were no statistical differences between Absorb BVS and XIENCE for any safety or effectiveness components for target lesion failure or for the secondary pre-specified outcomes. Panel members raised concerns with regard to the ABSORB III results and post hoc analyses focusing mainly on the noninferiority design of the trial, the apparent safety issues of the Absorb BVS in small vessels, the mismatch of visually versus intravascular imaging assessed vessel size found in ABSORB III and its implications on the adequate device labeling, the safety of Absorb BVS in specific patient and lesion subsets, and the post-approval commitments of the sponsor. CONCLUSIONS Following panel discussions and the evidence presented, the panel voted for approval of the device.

Embolic Protection Devices in Transcatheter Aortic Valve Replacement

The initially reported periprocedural neurological events rates associated with transcatheter aortic valve replacement raised concerns that ultimately led to the development and to the clinical research of novel embolic protection devices. Although the reduction of clinical stroke is a desired goal, the current research design of embolic protection devices focuses on surrogate markers of the clinical disease, primarily on silent central nervous system lesions observed in postprocedural diffuse-weighted magnetic resonance imaging and cognitive function testing. As the mere presence of particulate debris in brain matter may not correlate with the extent of brain injury, cognitive function, or quality of life, the clinical significance of embolic protection devices has yet to be determined, and interpretation of study results with regard to real-life clinical use should be viewed accordingly. The purpose of this article is to provide an overview of the updated ongoing clinical research on embolic protection devices and present its major caveats.

Contemporary transcatheter aortic valve replacement with third-generation balloon-expandable versus self-expanding devices

OBJECTIVES To evaluate balloon-expandable and self-expanding third-generation transcatheter aortic valve replacement (TAVR) devices according to patient selection criteria and outcomes. BACKGROUND Two competing third-generation TAVR technologies are currently commercially available in the US. There are no published head-to-head comparisons of the relative performance of these two devices. METHODS 257 consecutive patients undergoing TAVR with a third-generation balloon-expandable (Edwards Sapien 3) or self-expanding device (Medtronic CoreValve Evolut R) at a single US medical center were included. Choice of TAVR device was at the discretion of the multidisciplinary Heart Team. Baseline clinical characteristics, echocardiographic and CT imaging, procedural and 30-day outcomes were prospectively collected. RESULTS 74 patients received a self-expanding valve (SEV) and 183 received a balloon-expandable valve (BEV). Patients selected for SEV were more frequently women, with lower body surface area and smaller calcified iliofemoral arteries. Three SEV patients required implantation of a second valve to successfully treat paravalvular leak. Only one BEV patient had moderate paravalvular regurgitation. There was no difference in the rate of stroke, major vascular complication or bleeding. Permanent pacemaker implantation rate was significantly higher with SEV (12.7% vs 4.7%, P = 0.49) and hospital length of stay was longer (8.3% vs 6.5%, P = 0.043), but 30-day mortality was comparable (1.4% vs 1.6%, P = 1.00). CONCLUSIONS Short-term outcomes were equivalent between the two technologies. Clinically significant paravalvular regurgitation was rare. SEV were more frequently selected in women and patients with challenging transfemoral access, but were associated with higher permanent pacemaker implantation rate and longer hospital length of stay.

In-Stent Restenosis? The Raiders of the Magic Remedy

The introduction of bare metal stents (BMS) over 30 years ago was a significant milestone in the evolution of percutaneous coronary intervention. Soon after, it was apparent that these stents led to a troubling phenomenon of in-stent restenosis (ISR), which requires repeat revascularization, was associated with increased morbidity and mortality, and posed a therapeutic challenge. The quest for optimal therapy for ISR has begun, but in parallel, continued efforts were devoted to improve the stent technology. These iterations included design and alloy modification, reducing strut thickness, and adding a polymer to elute an antiproliferative drug. Drug-eluting stents (DES) significantly reduced the occurrence of exuberant neointimal proliferation.1 However, in spite of the wide use and experience gained with novel stent technologies and implantation techniques, the rates of ISR in both BMS and DES are still relatively high.2 In a contemporary report on a large cohort (n=10 004), routine angiographic surveillance 6 to 8 months after stent implantation has revealed ISR rates of 30.1%, 14.6%, and 12.2% for BMS, first-generation DES, and second-generation DES, respectively.3 See Article by Alfonso et al To optimize the treatment of ISR, it is imperative to identify and understand the major etiologies for ISR that have been traditionally classified and characterized as (1) operator or technique dependent, including stent undersizing, incomplete lesion coverage, stent under expansion, and malapposition; (2) mechanical and design properties of stents that may lead to recoil because of loss of radial force, stent fractures, and altering increase in shear stress; (3) patient- and biologically related conditions, such as metal allergy, local hypersensitivity reactions with immunologic and inflammatory response to the drug or the polymer, often characterized with inflammatory cells and smooth muscle cells that transformed to rigid scar tissue within the stent. This local inflammation can lead to the development of …

Does the new generation of drug-eluting stents render bare metal stents obsolete?

The development of bare metal coronary stents revolutionized the treatment of coronary artery disease by reducing rates of acute vessel closure and restenosis associated with balloon angioplasty. However, bare metal stents (BMS) resulted in high rates of restenosis and led to the development of drug-eluting stents (DES). Those first-generation DES were followed by successive generations of DES that included improvements, such as biodegradable and more biocompatible polymers. Despite the superiority of the current DES compared to BMS, a subset of patients still receives BMS. The following paper reviews the literature comparing the safety and efficacy of newer generation DES to BMS in such patients and ultimately challenges the use of BMS in contemporary current DES era.

Use of an ePTFE-covered nitinol self-expanding stent graft for the treatment off pre-closure device failure during transcatheter aortic valve replacement

OBJECTIVES Our aim was to describe our experience with the use of an ePTFE-covered nitinol self-expanding stent graft (GORE® VIABAHN® Endoprosthesis, Gore Medical, USA) placed in the common femoral artery for the treatment of suture-mediated pre-closure device failure following transcatheter aortic valve replacement (TAVR). BACKGROUND Access site-related vascular complications (VC) following sheath removal related to pre-closure device failure during TAVR are common and treatment options may vary. METHODS We performed an observational study on a series of consecutive patients who underwent TAVR between 2013 and 2015. RESULTS Included were 25 patients at a mean (±SD) age of 82±9. Failure of the closure device resulted in overt bleeding in 19 patients, dissection or no flow in 5 patients, and angiographic pseudoaneurysm in 1. Overall 29 stents were deployed with diameters ranging from 8 to 11mm and a length of 50mm (26, 90%). All stent-graft deployments achieved complete hemostasis of the arteriotomy site and resulted in normal flow to the distal vessels. None of the patients required open surgical repair. The mean hemoglobin drop was 2.6±1.3g/dl. Blood transfusions were used in 15 (60%) patients. Acute kidney injury occurred in 4 (16%) patients, none of whom was treated with dialysis. Length of hospital stay was 9±5days. All patients survived during a 30-day follow-up period, and none had VC related to the stented site. CONCLUSIONS The use of an ePTFE-covered Nitinol self-expanding stent graft is a feasible, safe, and effective treatment modality for access site-related VC following TAVR. SUMMARY The use of an ePTFE-covered nitinol self-expanding stent graft placed in the common femoral artery for the treatment of suture-mediated pre-closure device failure following transcatheter aortic valve replacement (TAVR) is described in 25 patients. Its use was found to be feasible, safe, and an effective treatment modality for access site-related vascular complications following TAVR.

Effect of Bleeding Risk on Type of Stent Used in Patients Presenting With Acute Coronary Syndrome

Patients at high bleeding risk (HBR) are at increased risk of bleeding following percutaneous coronary intervention (PCI) with drug-eluting stents (DES) due to the need for longer dual antiplatelet duration. We sought to evaluate the likelihood of receiving DES during PCI in HBR populations and to characterize DES utilization trends over time. Consecutive patients who underwent PCI from April 2003 to September 2015 were identified. HBR is defined as patients fulfilling 1 or more of the HBR criteria: age ≥75 years, anticoagulation use at discharge, history of stroke, cancer in previous 3 years, glucocorticoid use, hemoglobin (Hgb) <11 g/dl, platelet count <100,000/mm3, or creatinine clearance (CCr) <40 ml/min. Multivariate analysis was performed to identify which variables predicted DES selection. There were 10,594 patients (41.6%) who the met HBR definition. When adjusting for known risk factors, HBR patients were less likely to receive a DES compared with non-HBR patients (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.54 to 0.62, p <0.001). A preprocedural Hgb <11 g/dl had the greatest association with choosing DES during PCI (OR 0.51, 95% CI 0.45 to 0.57, p <0.001). Within the HBR patients, having 3 or more HBR criteria versus <3 HBR criteria had lower likelihood of receiving a DES (OR 0.50, 95% CI 0.44 to 0.57, p <0.001). In conclusion, presence of HBR has a significant impact upon the decision to use DES.

Overview of the 2016 US Food and Drug Administration Circulatory System Devices Panel Meeting on the AngelMed Guardian System

On March 16, 2016, the US Food and Drug Administration (FDA) convened a meeting of the Circulatory System Devices Panel to consider a premarket approval application for the AngelMed Guardian System based on the results of the pivotal ALERTS trial (AngelMed for Early Recognition and Treatment of STEMI) (URL: http://www.clinicaltrials.gov. Unique identifier: NCT00781118). The system comprises an implantable device similar to a single-chamber pacemaker, an external device that the patient carries, and a physician console. The device analyzes ST-segment shift through a single active-fixation lead in the right ventricular apex. If ST shift is identified, then the implantable device vibrates and the external device flashes and sounds an auditory alarm. More than 1 in 3 acute myocardial infarctions occur without chest pain, most commonly in women, diabetic patients, and the elderly. ST shift occurs rapidly in humans following coronary balloon occlusion.1 The AngelMed Guardian aims to reduce time to presentation by alerting the patient to ST shift even in the absence of symptoms. The ALERTS trial tested the safety and effectiveness of the Guardian System. A Bayesian adaptive design was used to adjust sample size based on interim treatment effect. The trial enrolled high-risk patients with a history of coronary artery disease (97% had previous revascularization). The trial was stopped early because of concerns that the predictive model did not accurately account for new Q waves. Nine hundred ten patients had the Guardian implanted (451 in the treatment arm versus 456 in the control arm with the device deactivated). Study …

Clinical Frailty as an Outcome Predictor After Transcatheter Aortic Valve Implantation

Society of Thoracic Surgeons (STS) score and frailty index are calculated routinely as part of transcatheter aortic valve implantation (TAVI) assessment to determine procedure risk. We aim to evaluate the incremental improvement of STS risk score using frailty status in predicting short- and long-term outcome after TAVI. Study population included 544 consecutive TAVI patients who completed full frailty assessment and STS score calculation before the procedure. Frailty is defined by the presence of any 3 of the following 5 criteria: algorithm-defined grip strength and 15-foot walking tests, body mass index < 20 kg/m2, Katz activity of daily living ≤ 4/6, serum albumin < 3.5 g/dl. Multivariable logistic analysis of 30-day and 1-year mortality was performed using a logistic regression model that comprised the STS risk score model as a single variable. Based on frailty definition, 242 patients were frail and 302 patients were not. STS score was higher in the frail group than in the nonfrail group. Compared with STS risk score alone, frailty status was a significant predictor of 1-year mortality after TAVI procedure (odds ratio 1.0, 95% confidence interval [CI] 1.0 to 1.1, p = 0.029 vs 2.75, 95% CI 1.55 to 4.87, p <0.001, respectively). Although the c-statistic of the 1-year STS risk prediction model only changed from 0.62 to 0.66 (p = 0.08), the net reclassification improvement increased significantly to 52.8% after adding frailty to the prediction model (95% CI 0.28 to 0.77, p <0.0001). Frailty status is associated with higher mortality in TAVI cohort and incrementally improves the well-validated STS risk prediction model. Frailty assessment should continue to be part of the preprocedural assessment to further improve patient outcomes after TAVI.

Utility of an additive frailty tests index score for mortality risk assessment following transcatheter aortic valve replacement

Background: The impact of frailty assessment on outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) remains unclear. Our aim was to evaluate the individual effect of each frailty test and the utility of an additive frailty index score on short‐ and long‐term survival following TAVR. Methods: Retrospective analysis of consecutive TAVR patients for whom a complete set of frailty tests was obtained: algorithm defined grip strength and 5‐m walking tests, body mass index <20 kg/m2, Katz activities of daily living ≤4/6, serum albumin <3.5 g/dL. Frailty status was defined as having 3 or more positive frailty tests. Included were 498 patients with a mean age of 82 ± 8 years. Results: Frailty status, observed in 266 (53%) patients, was associated with both 30‐day and 1‐year mortality (6% vs. 2%, P = .016; 20% vs. 9%, P < .001; within the respective frailty groups). As compared to 0–2 frailty criteria, a higher frailty index score was associated with increased risk of death at 1 year (OR 2.23; 95% CI 1.14–4.34; P = .019 and OR 3.30; 95% CI 1.36–8.00; P = .008 for 3 and 4–5 frailty criteria met, respectively). In Cox regression analysis, frailty status was correlated with 1‐year mortality (HR = 2.2; 95%CI 1.25–3.96; P = .007), and a higher frailty index was associated with increased mortality risk (HR = 2.0; 95% CI 1.08–3.7; P = .027; and HR = 3.07; 95% CI 1.4–6.7; P = .005; for any 3, and 4–5 frailty criteria, respectively). Conclusions: Frailty status and a higher frailty index score were associated with increased 1‐year mortality risk following TAVR.