Toby Rogers

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.

Feasibility of transcatheter aortic valve replacement in low-risk patients with symptomatic severe aortic stenosis: Rationale and design of the Low Risk TAVR (LRT) study

BACKGROUND Safety and effectiveness of transcatheter aortic valve replacement (TAVR) in low-risk patients with symptomatic severe aortic stenosis have not yet been established. HYPOTHESIS Transcatheter aortic valve replacement is feasible in patients with symptomatic severe aortic stenosis and low risk for surgical aortic valve replacement. DESIGN The LRT study is the first US Food and Drug Administration-approved Investigational Device Exemption prospective multicenter feasibility trial of TAVR in low-risk patients. Patients determined to be low risk by the Heart Team will be enrolled to undergo TAVR with a commercially available balloon-expandable or self-expandable device. A propensity score-matched, site-specific cohort of historical surgical aortic valve replacement patients will serve as a control group treated during the sites enrollment period or within the prior 3 years. Low-risk patients with symptomatic bicuspid aortic stenosis undergoing TAVR will be enrolled into a separate registry arm. All TAVR patients will undergo 4-dimensional contrast-enhanced cardiac computed tomography 4-6 weeks after implantation to assess for subclinical leaflet thrombosis and will be followed up clinically for 5 years with yearly echocardiography to monitor prosthesis function. SUMMARY The LRT study will test feasibility of TAVR in low-risk patients with symptomatic severe aortic stenosis in the United States with either tricuspid or bicuspid native aortic valves. Enrollment commenced in 2016 and results are expected in 2018.

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.

Temporal trends in patient referral for Transcatheter aortic valve replacement and reasons for exclusion at a high-volume Center in the United States

Background Clinical indications for transcatheter aortic valve replacement (TAVR) and elements of the implantation procedure, including delivery system miniaturization and novel access options, have evolved over time. The reasons patients are excluded from TAVR also have changed. The impact of these changes on patient referral for and exclusion from TAVR is unknown. Methods We retrospectively analyzed patients referred to our center for TAVR from January 2010 to August 2016 to evaluate reasons for patient exclusion. Patients were divided into three groups based on initial screening date for trends in demographics and exclusion: Group 1, 2010–2012; Group 2, 2012–2014; Group 3, 2014 to August 1, 2016. Annual trends for patient exclusion from TAVR were assessed. Results One thousand nine hundred fifty‐three patients were referred and underwent screening for TAVR. The rates at which patients were referred for TAVR were 23.8, 25.9, and 24.5 per month in groups 1, 2, and 3, respectively. Rate of patient exclusion from TAVR decreased from 68% in Group 1 to 38% in Group 3 (P < .001). The largest percentage of patients (29.4%) were initially excluded from TAVR for cardiac reasons, but this trend has decreased over time. Twenty‐five percent are excluded for lack of procedural indication. Exclusion from TAVR for vascular access reasons decreased from 7.9% in 2010 to 1.0% in 2016 (P = .017). Conclusions Referral numbers have been robust since TAVR became available. The percentage of patients excluded from TAVR has decreased over time. Patients are most commonly excluded from TAVR for concomitant coronary artery disease (CAD), asymptomatic severe AS, moderate AS, or non‐cardiac critical illness. Patients with CAD and those with asymptomatic severe AS or moderate AS should be a focus for continued research in TAVR.

Correlates and Significance of Elevation of Cardiac Biomarkers Elevation Following Transcatheter Aortic Valve Implantation

The Valve Academic Research Consortium-2 recommends cutoff levels of cardiac troponin of >15 and of creatine kinase MB (CKMB) of >5 of the upper limit of normal (ULN) as markers of periprocedural myocardial infarction. We aimed to evaluate the correlation of these cutoffs with the survival rate in patients who underwent transcatheter aortic valve implantation (TAVI) through the femoral access. Patients who underwent TAVI were classified according to the postprocedural peak marker level of >15 and >5 ULN for troponin and CKMB, respectively. Baseline characteristics were compared, and the impact of these markers on a 1-year survival rate was assessed. Of 474 patients who underwent TAVI, 77% had a peak troponin level of >15 ULN, whereas only 8% had a CKMB level of >5 ULN. Factors associated with troponin and CKMB elevations differed except for the preserved ejection fraction, which was associated with the elevation of both markers. Patients with troponin elevations had higher rates of postprocedure conduction defects (p = 0.001), whereas patients with CKMB had higher rates of bleeding (p <0.001) and stroke (p = 0.03). A troponin elevation of >15 ULN had no impact on the 1-year survival rate (p = 0.52); however, patients with a CKMB level of >5 ULN had increased mortality (p = 0.008), which remained significant in the multivariate analysis (hazard ratio = 2.02, p = 0.035). Troponin level and CKMB had a good correlation (r = 0.7), and a troponin level of 75 ULN was linked with a CKMB level of >5 ULN. In conclusion, cardiac markers differ in their peak levels above the ULN after TAVI. Careful attention should be taken for patients who underwent TAVI with a CKMB level of >5 ULN, as this is the only biomarker independently associated with survival rate.

ACUTE KIDNEY INJURY FOLLOWING PRIMARY PERCUTANEOUS CORONARY INTERVENTIONS FOR ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: TRENDS IN THE PAST FIFTEEN YEARS

Acute kidney injury (AKI) is a frequent complication after primary percutaneous coronary intervention (PPCI) following ST-segment elevation myocardial infarction (STEMI). In the period between 2000-2015, we evaluated the rates, correlates, and trends of AKI from a large single-center registry of