Andrew S. Mugglin

Surgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients

Background Although transcatheter aortic‐valve replacement (TAVR) is an accepted alternative to surgery in patients with severe aortic stenosis who are at high surgical risk, less is known about comparative outcomes among patients with aortic stenosis who are at intermediate surgical risk. Methods We evaluated the clinical outcomes in intermediate‐risk patients with severe, symptomatic aortic stenosis in a randomized trial comparing TAVR (performed with the use of a self‐expanding prosthesis) with surgical aortic‐valve replacement. The primary end point was a composite of death from any cause or disabling stroke at 24 months in patients undergoing attempted aortic‐valve replacement. We used Bayesian analytical methods (with a margin of 0.07) to evaluate the noninferiority of TAVR as compared with surgical valve replacement. Results A total of 1746 patients underwent randomization at 87 centers. Of these patients, 1660 underwent an attempted TAVR or surgical procedure. The mean (±SD) age of the patients was 79.8±6.2 years, and all were at intermediate risk for surgery (Society of Thoracic Surgeons Predicted Risk of Mortality, 4.5±1.6%). At 24 months, the estimated incidence of the primary end point was 12.6% in the TAVR group and 14.0% in the surgery group (95% credible interval [Bayesian analysis] for difference, ‐5.2 to 2.3%; posterior probability of noninferiority, >0.999). Surgery was associated with higher rates of acute kidney injury, atrial fibrillation, and transfusion requirements, whereas TAVR had higher rates of residual aortic regurgitation and need for pacemaker implantation. TAVR resulted in lower mean gradients and larger aortic‐valve areas than surgery. Structural valve deterioration at 24 months did not occur in either group. Conclusions TAVR was a noninferior alternative to surgery in patients with severe aortic stenosis at intermediate surgical risk, with a different pattern of adverse events associated with each procedure. (Funded by Medtronic; SURTAVI ClinicalTrials.gov number, NCT01586910.)

Combined Efficacy of Atrial Septal Lead Placement and Atrial Pacing Algorithms for Prevention of Paroxysmal Atrial Tachyarrhythmia

Introduction: The combined role of atrial septal lead location and atrial pacing algorithms in the prevention of atrial tachyarrhythmias (AT/AF), including both atrial fibrillation and flutter, is unknown. We tested the hypothesis that atrial prevention pacing algorithms could decrease AT/AF frequency in patients with atrial septal leads, bradycardia, and paroxysmal AT/AF.

Longevity of Sprint Fidelis Implantable Cardioverter-Defibrillator Leads and Risk Factors for Failure Implications for Patient Management

Background— Sprint Fidelis (Fidelis) implantable cardioverter-defibrillator leads are prone to fractures that have caused adverse events, primarily inappropriate shocks, and a few reported deaths. More than 100 000 patients have Fidelis leads. No independent multicenter long-term performance information exists for this lead, and single-center studies suggest that certain patients are at increased risk for Fidelis failure. Our aim was to assess the longevity of Fidelis leads and to evaluate clinical variables and adverse events associated with Fidelis failure. The results were compared with like data for Quattro Secure (Quattro) implantable cardioverter-defibrillator leads implanted at our centers. Methods and Results— This 3-center study included adults ≥18 years of age who received Fidelis or Quattro leads for the prevention of sudden cardiac death. From November 2001 to January 2009,1023 Fidelis and 1668 Quattro leads were implanted and followed up. The failure rate for Fidelis leads was 2.81%/y compared with 0.43%/y for Quattro leads (P<0.0001). No deaths or injuries occurred as a result of lead failure, but 42% of fractures caused inappropriate shocks. The survival of Fidelis leads at 4 years was 87.0% (95% confidence interval, 83.6 to 90.1) compared with 98.7% (95% confidence interval, 97.9 to 99.4) for Quattro leads (P<0.0001). Multivariate predictors of Fidelis failure were younger age (hazard ratio, 0.98; 95% confidence interval, 0.96 to 0.99), female gender (hazard ratio, 0.61; 95% confidence interval, 0.40 to 1.00), and cardiac disease (P=0.041). Conclusions— Compared with Quattro leads, the survival of Fidelis leads continues to decline, and Fidelis failure is notably higher in younger patients, women, individuals with hypertrophic cardiomyopathy, and patients with arrhythmogenic right ventricular dysplasia or channelopathies. These findings have significant implications for the management of patients who have Fidelis leads, and they demonstrate the importance of weighing clinical variables in assessments of implantable cardioverter-defibrillator lead performance.

Longevity of Sprint Fidelis Implantable Cardioverter-Defibrillator Leads and Risk Factors for Failure

Background— Sprint Fidelis (Fidelis) implantable cardioverter-defibrillator leads are prone to fractures that have caused adverse events, primarily inappropriate shocks, and a few reported deaths. More than 100 000 patients have Fidelis leads. No independent multicenter long-term performance information exists for this lead, and single-center studies suggest that certain patients are at increased risk for Fidelis failure. Our aim was to assess the longevity of Fidelis leads and to evaluate clinical variables and adverse events associated with Fidelis failure. The results were compared with like data for Quattro Secure (Quattro) implantable cardioverter-defibrillator leads implanted at our centers. Methods and Results— This 3-center study included adults ≥18 years of age who received Fidelis or Quattro leads for the prevention of sudden cardiac death. From November 2001 to January 2009,1023 Fidelis and 1668 Quattro leads were implanted and followed up. The failure rate for Fidelis leads was 2.81%/y compared with 0.43%/y for Quattro leads (P<0.0001). No deaths or injuries occurred as a result of lead failure, but 42% of fractures caused inappropriate shocks. The survival of Fidelis leads at 4 years was 87.0% (95% confidence interval, 83.6 to 90.1) compared with 98.7% (95% confidence interval, 97.9 to 99.4) for Quattro leads (P<0.0001). Multivariate predictors of Fidelis failure were younger age (hazard ratio, 0.98; 95% confidence interval, 0.96 to 0.99), female gender (hazard ratio, 0.61; 95% confidence interval, 0.40 to 1.00), and cardiac disease (P=0.041). Conclusions— Compared with Quattro leads, the survival of Fidelis leads continues to decline, and Fidelis failure is notably higher in younger patients, women, individuals with hypertrophic cardiomyopathy, and patients with arrhythmogenic right ventricular dysplasia or channelopathies. These findings have significant implications for the management of patients who have Fidelis leads, and they demonstrate the importance of weighing clinical variables in assessments of implantable cardioverter-defibrillator lead performance.

Fully model-based approaches for spatially misaligned data

Abstract We consider inference using multivariate data that are spatially misaligned; that is, involving variables (typically counts or rates) that are aggregated over differing sets of regional boundaries. Geographic information systems enable the simultaneous display of such datasets, but their current capabilities are essentially only descriptive, not inferential. We describe a hierarchical modeling approach that provides a natural solution to this problem through its ability to sensibly combine information from several sources of data and available prior information. Illustrating in the context of counts, allocation under nonnested regional grids is handled using conditionally independent Poisson-mullinomial models. Explanatory covariales and multilevel responses are also easily accommodated, with spatial correlation modeled using a conditionally autoregressive prior structure. Methods for dealing with missing values in spatial “edge zones” are also discussed. Like many recent hierarchical Bayesian applications, computing is implemented via a carefully tailored Metropolis-Hastings algorithm. We illustrate our method with a complex dataset involving inhalation exposure to radon emanating from a depleted uranium fuel processing plant in southwestern Ohio. Structure counts (obtained from U.S. Geological Survey topographical maps) are used to realign sex- and age group-specific U.S. census block group population counts onto a 160-cell circular “windrose” centered at the plant.

Safety and efficacy of a novel bioabsorbable, steroid-eluting sinus stent†

Inflammation/polyp recurrence, adhesions, and middle turbinate lateralization are causes of suboptimal outcomes following sinus surgery and lead to increased rates of revision. A bioabsorbable, drug‐eluting stent was evaluated for its ability to preserve sinus patency by providing controlled steroid delivery to the sinus mucosa. The study objective was to assess safety and efficacy of a steroid‐eluting sinus stent when used following functional endoscopic sinus surgery (FESS) in patients with chronic rhinosinusitis (CRS).

Advance II: a prospective, randomized study assessing safety and efficacy of bioabsorbable steroid-releasing sinus implants.

Objective. Endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) may be compromised by postoperative inflammation, polyposis, and adhesions, often requiring subsequent intervention. To address this issue, the authors investigated the safety and effectiveness of controlled delivery of mometasone furoate to the sinus mucosa via bioabsorbable implants deployed at the time of ESS. Study Design. Prospective, multicenter, randomized, controlled, double-blind trial using an intrapatient control design. Setting. Otolaryngology–head and neck surgery centers; both academic and private practices. Subjects and Methods. The study enrolled 105 patients with CRS undergoing bilateral ethmoidectomy to compare the effect of drug-releasing to non-drug-releasing implants using an intrapatient control design. Postoperative interventions, polyposis, and adhesions were assessed postoperatively. Efficacy was determined through independent analysis of randomized video-endoscopies by 3 blinded sinus surgeons. Safety assessments included ocular examinations. Results. Implants were successfully deployed in all 210 ethmoid sinuses. Compared with control sinuses with non-drug-releasing implants, the drug-releasing implant provided a 29.0% relative reduction in postoperative interventions (P = .028) and a 52% (P = .005) decrease in lysis of adhesions. The relative reduction in frank polyposis was 44.9% (P = .002). Similar reductions were observed in real-time grading performed by the clinical investigators. No clinically significant changes from baseline in intraocular pressure or cataracts were observed. Conclusion. This study provides a high level of evidence that use of steroid-releasing implants that apply a sustained release of corticosteroid improves surgical outcomes by reducing synechiae formation, polyposis, and the need for postoperative interventions, with no observable ocular safety risk.

Independent multicenter study of Riata and Riata ST implantable cardioverter-defibrillator leads.

BACKGROUND Riata and Riata ST leads (St Jude Medical, Sylmar, CA) are prone to failure. There are no independent multicenter reports regarding Riata or Riata ST lead performance. OBJECTIVE To conduct a retrospective multicenter study of Riata and Riata ST leads that were implanted and followed at 7 centers. METHODS The study included adults who received St Jude Medical Riata or Riata ST leads. Data for Quattro Secure leads were obtained from an earlier study. RESULTS From 2002 to 2010, 1081 patients received a Riata (n = 774) or Riata ST (n = 307) lead. Follow-up was longer for Riata than Riata ST leads (4.2 ± 2.4 years vs 3.3 ± 1.7 years; P<.0001). During the study, 67 leads failed (6.2%), including 62 of 774 Riata (8.0%) and 5 of 307 Riata ST (1.6%) leads. Forty-seven of 67 lead failures (70.1%) were caused by electrical malfunction, and 20 lead failures (29.9%) were due to externalized conductors (ECs) that were electrically intact. Of 110 leads examined fluoroscopically, ECs were found in 26 of 81 Riata (32%) and 1 of 29 Riata ST (3.4%) leads. Of 26 Riata leads with ECs, 7 (27%) were malfunctioning. Riata leads had lower overall and malfunction free survival compared to Quattro leads (P<.0001), while Riata ST lead survival was not different (P = .422). CONCLUSIONS The survival of Riata (but not Riata ST) leads was lower than Quattro leads; however, Riata ST leads had significantly shorter follow-up than Riata leads. ECs were common in Riata leads, and more than a quarter of Riata leads that had ECs were malfunctioning. Our observations suggest that systematic fluoroscopic examination of patients with Riata leads is appropriate.

Bayesian Areal Interpolation, Estimation, and Smoothing: An Inferential Approach for Geographic Information Systems

Geographic information systems (GISs) offer a powerful tool to geographers, foresters, statisticians, public health officials, and other users of spatially referenced regional data sets. However, as useful as they are for data display and trend detection, they typically feature little ability for statistical inference, leaving the user in doubt as to the significance of the various patterns and ‘hot spots’ identified. Unfortunately, classical statistical methods are often ill suited for this complex inferential task, dealing as it does with data which are multivariate, multilevel, misaligned, and often nonrandomly missing. In this paper we describe a Bayesian approach to this inference problem which simultaneously allows interpolation of missing values, estimation of the effect of relevant covariates, and spatial smoothing of underlying causal patterns. Implemented via Markov-chain Monte Carlo (MCMC) computational methods, the approach automatically produces both point and interval estimates which account for all sources of uncertainty in the data. After describing the approach in the context of a simple, idealized example, we illustrate it with a data set on leukemia rates and potential geographic risk factors in Tompkins County, New York, summarizing our results with numerous maps created by using the popular GIS Arc/INFO.

Effect of steroid-releasing sinus implants on postoperative medical and surgical interventions: an efficacy meta-analysis†

Endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) can be compromised by postoperative inflammation, polyposis, and adhesions, often requiring subsequent interventions. A bioabsorbable, steroid‐releasing sinus implant has been studied in 2 prospective, randomized clinical trials for its ability to preserve sinus patency and reduce medical and surgical interventions after ESS in patients with CRS. The objective of this study was to perform a meta‐analysis of the efficacy results from the 2 trials.