Frederic S. Resnic

A prospective feasibility trial investigating the use of the Impella 2.5 system in patients undergoing high-risk percutaneous coronary intervention (The PROTECT I Trial): initial U.S. experience

OBJECTIVES We sought to evaluate the safety and feasibility of the Impella 2.5 system (Abiomed Inc., Danvers, Massachusetts) in patients undergoing high-risk percutaneous coronary intervention (PCI). BACKGROUND The Impella 2.5 is a miniaturized percutaneous cardiac assist device, which provides up to 2.5 l/min forward flow from the left ventricle into the systemic circulation. METHODS In a prospective, multicenter study, 20 patients underwent high-risk PCI with minimally invasive circulatory support employing the Impella 2.5 system. All patients had poor left ventricular function (ejection fraction <or=35%) and underwent PCI on an unprotected left main coronary artery or last patent coronary conduit. Patients with recent ST-segment elevation myocardial infarction or cardiogenic shock were excluded. The primary safety end point was the incidence of major adverse cardiac events at 30 days. The primary efficacy end point was freedom from hemodynamic compromise during PCI (defined as a decrease in mean arterial pressure below 60 mm Hg for >10 min). RESULTS The Impella 2.5 device was implanted successfully in all patients. The mean duration of circulatory support was 1.7 +/- 0.6 h (range: 0.4 to 2.5 h). Mean pump flow during PCI was 2.2 +/- 0.3 l/min. At 30 days, the incidence of major adverse cardiac events was 20% (2 patients had a periprocedural myocardial infarction; 2 patients died at days 12 and 14). There was no evidence of aortic valve injury, cardiac perforation, or limb ischemia. Two patients (10%) developed mild, transient hemolysis without clinical sequelae. None of the patients developed hemodynamic compromise during PCI. CONCLUSIONS The Impella 2.5 system is safe, easy to implant, and provides excellent hemodynamic support during high-risk PCI. (The PROTECT I Trial; NCT00534859).

Association of Public Reporting for Percutaneous Coronary Intervention with Utilization and Outcomes among Medicare beneficiaries with Acute Myocardial Infarction

CONTEXT Public reporting of patient outcomes is an important tool to improve quality of care, but some observers worry that such efforts will lead clinicians to avoid high-risk patients. OBJECTIVE To determine whether public reporting for percutaneous coronary intervention (PCI) is associated with lower rates of PCI for patients with acute myocardial infarction (MI) or with higher mortality rates in this population. DESIGN, SETTING, AND PATIENTS Retrospective observational study conducted using data from fee-for-service Medicare patients (49,660 from reporting states and 48,142 from nonreporting states) admitted with acute MI to US acute care hospitals between 2002 and 2010. Logistic regression was used to compare PCI and mortality rates between reporting states (New York, Massachusetts, and Pennsylvania) and regional nonreporting states (Maine, Vermont, New Hampshire, Connecticut, Rhode Island, Maryland, and Delaware). Changes in PCI rates over time in Massachusetts compared with nonreporting states were also examined. MAIN OUTCOME MEASURES Risk-adjusted PCI and mortality rates. RESULTS In 2010, patients with acute MI were less likely to receive PCI in public reporting states than in nonreporting states (unadjusted rates, 37.7% vs 42.7%, respectively; risk-adjusted odds ratio [OR], 0.82 [95% CI, 0.71-0.93]; P = .003). Differences were greatest among the 6708 patients with ST-segment elevation MI (61.8% vs 68.0%; OR, 0.73 [95% CI, 0.59-0.89]; P = .002) and the 2194 patients with cardiogenic shock or cardiac arrest (41.5% vs 46.7%; OR, 0.79 [95% CI, 0.64-0.98]; P = .03). There were no differences in overall mortality among patients with acute MI in reporting vs nonreporting states. In Massachusetts, odds of PCI for acute MI were comparable with odds in nonreporting states prior to public reporting (40.6% vs 41.8%; OR, 1.00 [95% CI, 0.71-1.41]). However, after implementation of public reporting, odds of undergoing PCI in Massachusetts decreased compared with nonreporting states (41.1% vs 45.6%; OR, 0.81 [95% CI, 0.47-1.38]; P = .03 for difference in differences). Differences were most pronounced for the 6081 patients with cardiogenic shock or cardiac arrest (prereporting: 44.2% vs 36.6%; OR, 1.40 [95% CI, 0.85-2.32]; postreporting: 43.9% vs 44.8%; OR, 0.92 [95% CI, 0.38-2.22]; P = .03 for difference in differences). CONCLUSIONS Among Medicare beneficiaries with acute MI, the use of PCI was lower for patients treated in 3 states with public reporting of PCI outcomes compared with patients treated in 7 regional control states without public reporting. However, there was no difference in overall acute MI mortality between states with and without public reporting.

Long-Term Clinical Outcomes After Drug-Eluting and Bare-Metal Stenting in Massachusetts

Background— Drug-eluting stents (DES) reduce the need for repeat revascularization, but their long-term safety relative to that of bare-metal stents (BMS) in general use remains uncertain. We sought to compare the clinical outcome of patients treated with DES with that of BMS. Methods and Results— All adults undergoing percutaneous coronary intervention with stenting between April 1, 2003, and September 30, 2004, at non–US government hospitals in Massachusetts were identified from a mandatory state database. Patients were classified from the index admission according to stent types used. Clinical and procedural risk factors were collected prospectively. Risk-adjusted mortality, myocardial infarction, and revascularization rate differences (DES−BMS) were estimated through propensity score matching without replacement. A total of 11 556 patients were treated with DES, and 6237 were treated with BMS, with unadjusted 2-year mortality rates of 7.0% and 12.6%, respectively (P<0.0001). In 5549 DES patients matched to 5549 BMS patients, 2-year risk-adjusted mortality rates were 9.8% and 12.0%, respectively (P=0.0002), whereas the respective rates for myocardial infarction and target-vessel revascularization were 8.3% versus 10.3% (P=0.0005) and 11.0% versus 16.8% (P<0.0001). Conclusions— DES treatment was associated with lower rates of mortality, myocardial infarction, and target-vessel revascularization than BMS treatment in similar patients in a matched population-based study. Comprehensive follow-up in this inclusive population is warranted to identify whether similar safety and efficacy remain beyond 2 years.

Bleeding avoidance strategies. Consensus and controversy.

Bleeding complications after coronary intervention are associated with prolonged hospitalization, increased hospital costs, patient dissatisfaction, morbidity, and 1-year mortality. Bleeding avoidance strategies is a term incorporating multiple modalities that aim to reduce bleeding and vascular complications after cardiovascular catheterization. Recent improvements in the rates of bleeding complications after invasive cardiovascular procedures suggest that the clinical community has successfully embraced specific strategies and improved patient care in this area. There remains controversy regarding the efficacy, safety, and/or practicality of 3 key bleeding avoidance strategies for cardiac catheterization and coronary intervention: procedural (radial artery approach, safezone arteriotomy), pharmacological (multiple agents), and technological (vascular closure devices) approaches to improved access. In this paper, we address areas of consensus with respect to selected modalities in order to define the role of each strategy in current practice. Furthermore, we focus on areas of controversy for selected modalities in order to define key areas warranting cautious clinical approaches and the need for future randomized clinical trials in this area.

The Public Health Hazards of Risk Avoidance Associated With Public Reporting of Risk-Adjusted Outcomes in Coronary Intervention

Public reporting of risk-adjusted outcomes for percutaneous coronary intervention (PCI) procedures has been mandated in New York State for more than a decade. During that time there has been a significant decline in the unadjusted mortality after such procedures. Massachusetts joined New York in 2003 as only the second state to require case level reporting of every coronary interventional procedure performed. In this review, we explore the differences in the populations reported by the 2 states and consider possible risks of public reporting of clinical outcomes after PCI procedures, including the risk of increasing conservatism in the treatment of the sickest patients. We offer a conceptual framework to understand the potential risk-averse behavior of interventional cardiologists subject to public reporting, and offer several proposals to counteract this potential deleterious effect of reporting programs.

Vascular closure devices and the risk of vascular complications after percutaneous coronary intervention in patients receiving glycoprotein IIb-IIIa inhibitors

Vascular closure devices offer advantages over traditional means of obtaining hemostasis after percutaneous coronary intervention (PCI) in terms of patient comfort and time to ambulation. We investigate whether such devices also reduce the risk of vascular complications in selected patient populations. We conducted a retrospective analysis of all patients who underwent PCI at our institution between January 1998 and December 1999. Of 3,151 consecutive patients, 3,027 were eligible to receive vascular closure devices. Of these, 1,485 received a closure device and 1,409 received glycoprotein IIb-IIIa antagonists. The overall vascular complication rate, as defined by the need for surgical repair or transfusion, or the development of arteriovenous fistula, pseudoaneurysm, or large hematoma, was 4.20%. By univariate analysis, the use of closure devices was associated with a lower vascular complication rate (3.03% vs 5.52%; p = 0.002) and a shorter length of hospital stay (2.77 vs 3.97 days, p <0.001). Multivariate analysis showed a significant reduction in vascular complications with closure devices (odds ratio 0.59, p = 0.007). For the subgroup of patients receiving glycoprotein IIb-IIIa antagonists, the use of closure devices was associated with an even more pronounced reduction in the risk of vascular complications (odds ratio 0.45, p <0.008). Thus, the use of closure devices in selected patients undergoing PCI is associated with a low rate of vascular complications and decreased length of stay. This benefit was most marked for patients receiving glycoprotein IIb-IIIa antagonists.

iDASH: integrating data for analysis, anonymization, and sharing

iDASH (integrating data for analysis, anonymization, and sharing) is the newest National Center for Biomedical Computing funded by the NIH. It focuses on algorithms and tools for sharing data in a privacy-preserving manner. Foundational privacy technology research performed within iDASH is coupled with innovative engineering for collaborative tool development and data-sharing capabilities in a private Health Insurance Portability and Accountability Act (HIPAA)-certified cloud. Driving Biological Projects, which span different biological levels (from molecules to individuals to populations) and focus on various health conditions, help guide research and development within this Center. Furthermore, training and dissemination efforts connect the Center with its stakeholders and educate data owners and data consumers on how to share and use clinical and biological data. Through these various mechanisms, iDASH implements its goal of providing biomedical and behavioral researchers with access to data, software, and a high-performance computing environment, thus enabling them to generate and test new hypotheses.

Postmarketing Surveillance of Medical Devices — Filling in the Gaps

Failures of implantable medical devices can carry substantial risk of serious injury, and effective systems for monitoring safety after marketing begins are essential. Several FDA initiatives have been launched to fill the gaps in the passive event-reporting system.

Risk Predictors of Retroperitoneal Hemorrhage Following Percutaneous Coronary Intervention

Retroperitoneal hemorrhage (RPH) is a potentially catastrophic complication after percutaneous coronary intervention (PCI). Previous studies identified female gender, body surface area, and high arterial puncture location as independent risk factors for RPH. There have been conflicting reports regarding the association with vascular closure devices (VCDs). Chronic renal insufficiency (CRI) and diabetes mellitus have been associated with both peripheral vascular disease and vascular access-site complications. The putative association of VCDs, CRI, and diabetes mellitus with RPH in the contemporary PCI era was investigated. A total of 3,062 consecutive patients undergoing 3,482 PCIs at Brigham and Womens Hospital from January 2005 to April 2007 were evaluated for the study. All 3,311 patients with femoral angiography underwent hand-caliper-based quantitative vascular analysis and were included in this analysis. Multivariate analysis was performed using a backwards selection algorithm, and a propensity adjustment was developed to control for possible confounding variables regarding VCD use. The incidence of RPH was 0.49% (17 of 3,482 patients). After multivariate and propensity analyses, covariates that significantly influenced the risk of RPH were CRI, glycoprotein IIb/IIIa inhibitors, and high arterial puncture (p < or =0.007). VCD use was not independently associated with the development of RPH (p = 0.74). In conclusion, this large prospective cohort study identified CRI, but not VCD use, as an independent predictor for RPH and peripheral vascular disease.

Discrimination and calibration of mortality risk prediction models in interventional cardiology

OBJECTIVES Using a local percutaneous coronary intervention (PCI) data repository, we sought to compare the performance of a number of local and well-known mortality models with respect to discrimination and calibration. BACKGROUND Accurate risk prediction is important for a number of reasons including physician decision support, quality of care assessment, and patient education. Current evidence on the value of applying PCI risk models to individual cases drawn from a different population is controversial. METHODS Data were collected from January 01, 2002 to September 30, 2004 on 5216 consecutive percutaneous coronary interventions at Brigham and Womens Hospital (Boston, MA). Logistic regression was used to create a local risk model for in-hospital mortality in these procedures, and a number of statistical methods were used to compare the discrimination and calibration of this new and old local risk models, as well as the Northern New England Cooperative Group, New York State (1992 and 1997), University of Michigan consortium, American College of Cardiology-National Cardiovascular Data Registry, and The Cleveland Clinic Foundation risk prediction models. Areas under the ROC (AUC) curves were used to evaluate discrimination, and the Hosmer-Lemeshow (HL) goodness-of-fit test and calibration curves assessed applicability of the models to individual cases. RESULTS Multivariate risk factors included in the newly constructed local model were: age, prior intervention, diabetes, unstable angina, salvage versus elective procedure, cardiogenic shock, acute myocardial infarction (AMI), and left anterior descending artery intervention. The area under the ROC curve (AUC) was 0.929 (SE=0.017), and the p value for the Hosmer-Lemeshow (HL) goodness-of-fit was 0.473. This indicates good discrimination and calibration. Bootstrap re-sampling indicated AUC stability. Evaluation of the external models showed an AUC range from 0.82 to 0.90 indicating good discrimination across all models, but poor calibration (HL p value < or = 0.0001). CONCLUSIONS Validation of AUC values across all models suggests that certain risk factors have remained important over the last decade. However, the lack of calibration suggests that small changes in patient populations and data collection methods quickly reduce the accuracy of patient level estimations over time. Possible solutions to this problem involve either recalibration of models using local data or development of new local models.