Preclinical Assessment of a Novel Conformable Foam-Based Left Atrial Appendage Closure Device.

BACKGROUND: Left atrial appendage (LAA) occlusion has been established as an alternative to systemic anticoagulation for stroke prevention in patients with atrial fibrillation; however, limitations of current devices have slowed adoption. We present preclinical evaluations of a novel device, the Conformal Left Atrial Appendage Seal (CLAAS). METHODS: An in vitro assessment of conformability was conducted to evaluate the two CLAAS devices (regular 27 mm and large 35 mm) and a Watchman 2.5 (27 mm). Devices were placed within silicone tubes and compressed in a vise submerged in a water bath at 37°C. Changes in device diameter and visual seal were noted. Acute (n = 1) and chronic 60-day (n = 6) canine studies with gross and histologic assessment were performed. RESULTS: Conformability bench tests demonstrated that the regular CLAAS implant was able to seal oval orifices from 20 × 30 mm to 15 × 33 mm and the large from 30 × 35 mm to 20 × 40 mm. As the CLAAS implant was compressed in the minor diameter, it increased in the major diameter, thereby filling the oval space, whereas the Watchman 2.5 showed gaps and maintained its round configuration when compressed in one direction. Seven devices were successfully implanted in the canine model with complete seal without thrombus. Histologic examination showed complete neointima covering with minimal inflammation at 60 days. CONCLUSIONS: Preclinical testing demonstrated the conformability of the CLAAS implant and its ability to seal the LAA. Clinical studies are ongoing to characterize the utility of the CLAAS implant in the treatment of patients with atrial fibrillation.

Funding of Studies Supporting IA Guideline Recommendations in Cardiovascular Medicine-A Systematic Review.

Each guideline recommendation from the American Heart Association and the American College of Cardiology includes an indication of the level of supporting evidence and the associated strength of recommendation with "IA" recommendations representing those with the highest quality supporting evidence and the least amount of uncertainty for benefit. In this analysis, study type and funding sources were systematically tabulated across these IA guideline recommendations over the past 5 years. Nearly half of studies supporting IA guideline recommendations were randomized controlled trials (45%). Overall, about one third of studies supporting IA recommendations were publicly funded (34.9%) with slightly more funded through industry sources (43.5%). Funding sources varied based on the type of intervention being studied with randomized controlled trials of device, diagnostic, and pharmacological interventions reflecting predominantly industry-funded studies. Over time, studies supporting IA cardiology guideline are funded by industry about twice as often as public sources. Thus, data of adequate quality to support cardiovascular guideline recommendations come from a variety of sources.

Atrial Fibrillation and Stent Selection (Bare Metal vs Drug Eluting) (from Medicare Claims).

In treating coronary artery disease, many factors influence the choice of bare metal stent (BMS) or drug-eluting stent (DES), including bleed risk and suitability for prolonged dual antiplatelet therapy. Atrial fibrillation (AF) further complicates this choice, due to common use of anticoagulation. We examined stent selection in the United States by AF status and across academic medical centers (AMCs) to explore how cardiologists are managing this complex choice. Using a 100% Medicare denominator file and associated claims (2008 to 2012), we identified patients over age 65 receiving inpatient coronary artery stents. We measured BMS and DES use in patients with AF and in patients without AF and assessed variation in stent choice across AMCs, adjusting for differences in age, gender, and race. We identified 898,788 stent episodes among elderly Medicare beneficiaries. BMS, as a percentage of total inpatient stent episodes, decreased from 2008 to 2012, in patients with AF (42% to 34%) and in patients without AF (32% to 23%). Across AMCs, adjusted stent choice varied substantially, but more so for patients with AF (2008 to 2012 median BMS 44% to 39%, annual interquartile ratios range 1.8 to 2.3) than patients without AF (2008 to 2012 median BMS 33% to 25%, annual interquartile ratios range 2.0 to 1.8). In conclusion, among stent recipients, patients with AF are more likely to receive BMS than patients without AF but treatment varies across systems, suggesting a lack of consensus. Studies of stent choice and outcomes among patients with AF are needed to guide care decisions and optimize outcomes.

Optical coherence tomography versus intravascular ultrasound in the evaluation of observer variability and reliability in the assessment of stent deployment: the OCTIVUS study.

OBJECTIVES: To compare the variability in the assessment of coronary stents among interventional cardiologists (readers) using optical coherence tomography (OCT) and intravascular ultrasound (IVUS). BACKGROUND: IVUS is established and validated in the evaluation of coronary stent. For cardiologists without core lab expertise, the utility of IVUS is limited by image quality. OCT yields higher image resolution; however, the consistency with which these readers interpret OCT images has not been fully evaluated or compared with IVUS. METHODS: OCT and IVUS image sets (five pairs) obtained after stent placement were reviewed by readers with clinical experience in both modalities. Parameters assessed included stent expansion and symmetry, reference vessel and in-stent cross-sectional area (CSA) and diameter, and stent strut apposition as well as Multicenter Ultrasound Stenting in Coronaries criteria. These interpretations were compared with core lab readings and examined for interobserver variability. RESULTS: The interobserver variability for measurement of in-stent CSA was 1.34 mm(2) using IVUS compared with 0.85 mm(2) using OCT (P = 0.024). Variation in the deviation from core lab measurement of in-stent CSA for IVUS was 1.48 mm(2) compared with 0.87 mm(2) for OCT (P = 0.042). The interobserver agreement for obtaining the Multicenter Ultrasound Stenting in Coronaries criteria using IVUS was 80.4% compared with 81.1% using OCT (P = 0.78). Compared with the corelab measurement, the readers obtained an agreement of 72.7% using IVUS vs. 67.3% using OCT (P = 0.43). CONCLUSION: In the assessment of deployed coronary stents by practicing cardiologists, OCT images are interpreted more consistently compared with IVUS and can be used to assess stent deployment using IVUS-validated metrics.

Assessment with optical coherence tomography of a new strategy for bifurcational lesion treatment: the Tryton Side-Branch Stent.

The Tryton-Side Branch Stent (Tryton Medical, Inc., Newton, MA, USA) is a dedicated stent designed to provide complete carinal coverage of bifurcational lesions. After implantation of a 18 mm cobalt chromium Tryton stent from the left circumflex into the obtuse marginal branch, recrossing with an everolimus eluting Promus stent and final kissing balloon dilatation, optical coherence tomography (OCT) (LightLab Imaging Inc., Westford, MA, USA) was performed with a non-occlusive technique with motorized pullback (3 mm/s) during continuous pump injection of iso-osmolar contrast, in both LCx and OM1. OCT imaging showed good strut apposition at the level of the carina, with full coverage and no stent protrusion at the ostium of the side branch. Few malapposed struts were present in the proximal main vessel in the segment of stent superimposition, with a maximal separation from to the vessel wall of 160 microm. The implantation of the Tryton-Side Branch Stent allowed full coverage of the side branch ostium with uniform apposition of the stent struts at the level of the carina assessed by OCT.

Transient and persistent renal dysfunction are predictors of survival after percutaneous coronary intervention: insights from the Dartmouth Dynamic Registry.

OBJECTIVES: We sought to determine if transient and persistent elevations in creatinine following percutaneous coronary intervention (PCI) resulted in poor survival. BACKGROUND: Limited survival data exist that defines the natural survival history of transient and persistent renal dysfunction following interventional PCI cases. METHODS: Data were collected prospectively on 7,856 consecutive patients undergoing PCI from January 1, 2000 to July 31, 2006. Ninety-three patients were excluded due to pre-PCI dialysis. Patients were stratified into three categories of renal dysfunction: no renal dysfunction from baseline (<0.5 mg/dL increase in creatinine within 48 hr of the procedure), transient renal dysfunction (> or =0.5 mg/dL increase in creatinine within 48 hr with return to normal within 2 weeks), and persistent renal dysfunction (> or =0.5 mg/dL increase in creatinine without returning to normal within 2 weeks of the procedure). Mortality was determined by comparing with the Social Security Death Master File. RESULTS: Median survival was 3.2 years (mean 3.4). Renal dysfunction occurred in 250 patients (0.5 mg/dL increase in creatinine). Survival was significantly different between patients at 1, 3.2, and 7.5 years (P-value < 0.001): no renal dysfunction (95%, 88%, 75%), with transient (61%, 42%, 0%), and with persistent (58%, 44%, 36%) renal dysfunction. Patients with transient or persistent renal dysfunction had a twofold-threefold increased risk of 7.5-year mortality compared with patients with no renal dysfunction. CONCLUSIONS: Both transient and persistent postprocedural renal dysfunction are prognostically significant for mortality during extended follow-up. Renal dysfunction should be closely monitored before and after PCI.

Outcomes following coronary stenting in the era of bare-metal vs the era of drug-eluting stents.

CONTEXT: Although drug-eluting stents reduce restenosis rates relative to bare-metal stents, concerns have been raised that drug-eluting stents may also be associated with an increased risk of stent thrombosis. Our study focused on the effect of stent type on population-based interventional outcomes. OBJECTIVE: To compare outcomes of Medicare beneficiaries who underwent nonemergent coronary stenting before and after the availability of drug-eluting stents. DESIGN, SETTING, AND PATIENTS: Observational study of 38,917 Medicare patients who underwent nonemergent coronary stenting from October 2002 through March 2003 when only bare-metal stents were available (bare-metal stent era cohort) and 28,086 similar patients who underwent coronary stenting from September through December 2003, when 61.5% of patients received a drug-eluting stent and 38.5% received a bare-metal stent (drug-eluting stent era cohort). Follow-up data were available through December 31, 2005. MAIN OUTCOME MEASURES: Coronary revascularization (percutaneous coronary intervention, coronary artery bypass surgery), ST-elevation myocardial infarction, survival through 2 years of follow-up. RESULTS: Relative to the bare-metal stent era, patients treated in the drug-eluting stent era had lower 2-year risks for repeat percutaneous coronary interventions (17.1% vs 20.0%, P < .001) and coronary artery bypass surgery (2.7% vs 4.2%, P < .01). The difference in need for repeat revascularization procedures between these 2 eras remained significant after risk adjustment (hazard ratio, 0.82; 95% confidence interval, 0.79-0.85). There was no difference in unadjusted mortality risks at 2 years (8.4% vs 8.4%, P =.98 ), but a small decrease in ST-elevation myocardial infarction existed (2.4% vs 2.0%, P < .001). The adjusted hazard of death or ST-elevation myocardial infarction at 2 years was similar (hazard ratio, 0.96; 95% confidence interval, 0.92-1.01). CONCLUSION: The widespread adoption of drug-eluting stents into routine practice was associated with a decline in the need for repeat revascularization procedures and had similar 2-year risks for death or ST-elevation myocardial infarction to bare-metal stents.

Medical device development: managing conflicts of interest encountered by physicians.

New technologies introduced over the past three decades have transformed medical diagnosis and treatment, and significantly improved patient outcomes. These changes have been mediated by the introduction of new medical devices, particularly for the treatment of cardiovascular, orthopedic, and ophthalmic disorders. These devices, in turn, have created large markets and spawned a burgeoning medical device industry, including six Fortune 500 companies whose combined market capitalization now exceeds 400 billion dollars. This success story, which has unquestionably benefited patients and society alike, has been dependent upon an intense collaboration among industry, clinicians, and regulatory authorities. However, when physicians actively involved in patient care participate in such collaborations, they are increasingly vulnerable to creating potential conflicts between these two (clinical and device development) roles. Such conflicts, which may ultimately erode public trust, have important consequences not only for the individual physicians, but also for their parent institutions, their patients, sponsoring companies, and the entire clinical research enterprise that makes the development and introduction of new devices possible. The third Dartmouth Device Development Symposium held in October 2005 brought together thought leaders within the medical device community, including academicians, clinical investigators, regulators from the Food and Drug Administration and Centers for Medicare and Medicaid Services (CMS), large and small device manufacturers and the financial (venture capital and investment banks) community. The Symposium examined the conflicts of interest encountered during the early development and commercialization of a medical device. The goal of these discussions was to (1) identify and characterize the conflicts that arise and (2) provide strategies to address these conflicts. This manuscript was prepared by a writing committee to provide a summary report of those discussions.

Postmarketing surveillance of medical devices using Medicare claims.

The current system of postmarketing surveillance of high-risk medical devices could be improved by taking advantage of the administrative billing data collected by the Centers for Medicare and Medicaid Services (CMS) to systematically monitor for adverse events that may signal device-related problems. In this paper we use the current concern about the excess risk associated with drug-eluting coronary stents to highlight the strengths and weaknesses of claims data for postmarketing surveillance and propose a pilot collaboration between government, industry, and academe to systematically explore the use of Medicare claims data for this purpose.