Neil J. Wimmer

Liberal versus restrictive transfusion thresholds for patients with symptomatic coronary artery disease.

BACKGROUND Prior trials suggest it is safe to defer transfusion at hemoglobin levels above 7 to 8 g/dL in most patients. Patients with acute coronary syndrome may benefit from higher hemoglobin levels. METHODS We performed a pilot trial in 110 patients with acute coronary syndrome or stable angina undergoing cardiac catheterization and a hemoglobin <10 g/dL. Patients in the liberal transfusion strategy received one or more units of blood to raise the hemoglobin level ≥10 g/dL. Patients in the restrictive transfusion strategy were permitted to receive blood for symptoms from anemia or for a hemoglobin <8 g/dL. The predefined primary outcome was the composite of death, myocardial infarction, or unscheduled revascularization 30 days post randomization. RESULTS Baseline characteristics were similar between groups except age (liberal, 67.3; restrictive, 74.3). The mean number of units transfused was 1.6 in the liberal group and 0.6 in the restrictive group. The primary outcome occurred in 6 patients (10.9%) in the liberal group and 14 (25.5%) in the restrictive group (risk difference = 15.0%; 95% confidence interval of difference 0.7% to 29.3%; P = .054 and adjusted for age P = .076). Death at 30 days was less frequent in liberal group (n = 1, 1.8%) compared to restrictive group (n = 7, 13.0%; P = .032). CONCLUSIONS The liberal transfusion strategy was associated with a trend for fewer major cardiac events and deaths than a more restrictive strategy. These results support the feasibility of and the need for a definitive trial.

A Prediction Model to Identify Patients at High Risk for 30-Day Readmission After Percutaneous Coronary Intervention

Background—The Affordable Care Act creates financial incentives for hospitals to minimize readmissions shortly after discharge for several conditions, with percutaneous coronary intervention (PCI) to be a target in 2015. We aimed to develop and validate prediction models to assist clinicians and hospitals in identifying patients at highest risk for 30-day readmission after PCI. Methods and Results—We identified all readmissions within 30 days of discharge after PCI in nonfederal hospitals in Massachusetts between October 1, 2005, and September 30, 2008. Within a two-thirds random sample (Developmental cohort), we developed 2 parsimonious multivariable models to predict all-cause 30-day readmission, the first incorporating only variables known before cardiac catheterization (pre-PCI model), and the second incorporating variables known at discharge (Discharge model). Models were validated within the remaining one-third sample (Validation cohort), and model discrimination and calibration were assessed. Of 36 060 PCI patients surviving to discharge, 3760 (10.4%) patients were readmitted within 30 days. Significant pre-PCI predictors of readmission included age, female sex, Medicare or State insurance, congestive heart failure, and chronic kidney disease. Post-PCI predictors of readmission included lack of &bgr;-blocker prescription at discharge, post-PCI vascular or bleeding complications, and extended length of stay. Discrimination of the pre-PCI model (C-statistic=0.68) was modestly improved by the addition of post-PCI variables in the Discharge model (C-statistic=0.69; integrated discrimination improvement, 0.009; P<0.001). Conclusions—These prediction models can be used to identify patients at high risk for readmission after PCI and to target high-risk patients for interventions to prevent readmission.

Risk Prediction for Adverse Events After Carotid Artery Stenting in Higher Surgical Risk Patients

Background and Purpose— The goal of carotid artery stenting is to decrease the risk of stroke or other adverse events from carotid artery disease. Choosing a treatment strategy requires patient-specific information regarding periprocedural risk of adverse neurologic events. The aim of this study was to predict individual patient risk after carotid artery stenting in patients at higher risk for carotid endarterectomy. Methods— Subjects enrolled in the Stenting and Angioplasty with Protection in Patients at High-Risk for Endarterectomy (SAPPHIRE) worldwide study underwent carotid artery stenting with distal protection. Only patients with at least 1 anatomic or comorbid factor associated with elevated surgical risk were included. Preprocedural factors were used to develop a model and integer-based risk score predicting stroke or death within 30 days. The model was calibrated and internally validated using bootstrap resampling. Results— Ten thousand one hundred eighty-six patients were included in the analysis. The overall rate of stroke or death was 3.6% at 30 days after carotid artery stenting. Independent predictors of adverse outcomes were increased age (P=0.006), history of stroke (P<0.001), history of transient ischemic attack presentation (P=0.001), recent (<4 weeks) myocardial infarction (P=0.006), dialysis treatment (P=0.007), need for cardiac surgery in addition to carotid revascularization (P=0.005), a right-sided carotid stenosis (P=0.006), a longer carotid plaque (P=0.012), the presence of a Type II or III aortic arch (P=0.035), and a tortuous carotid arterial system (P=0.004). The optimism-adjusted C-statistic was 0.691. Conclusions— Commonly collected clinical and anatomic variables can identify patients at high and low risk for stroke or death after carotid artery stenting.

Association Between Operator Procedure Volume and Patient Outcomes in Percutaneous Coronary Intervention A Systematic Review and Meta-Analysis

Background—The growth of centers capable of performing percutaneous coronary intervention (PCI) has outpaced population growth despite declining incidence of myocardial infarction and prevalence of coronary artery disease, potentially increasing the proportion of operators falling below minimal yearly volume standards set by professional societies. Methods and Results—Electronic literature search of MEDLINE and the Cochrane Library for English-language articles published between 1977 and November 2012 was performed. Title and abstract review followed by full-text and references review were performed by 2 authors independently to identify studies examining the association between operator volume and outcomes in PCI. Using a standardized form, 2 authors abstracted information on study design, methods, outcomes, statistical methods, and conclusions. Studies were categorized according to methodological quality and outcomes. Meta-analyses were performed by outcome using a random-effects model. Of the 23 studies included in the analysis, 14 (61%) evaluated mortality, 7 (30%) evaluated major adverse cardiac events, and 2 (9%) evaluated angiographic success. In total, the studies evaluated 15 907 operators performing 205 214 PCIs on 1 109 103 patients at 2456 centers with a mean follow-up of 2.8 years. Eleven (48%) were considered higher quality. Studies with higher methodological quality and large sample sizes more often showed a relationship between operator volume and outcomes in PCI. Higher volume was associated with improved major adverse cardiac events at every threshold, regardless of the threshold evaluated. Conclusions—Mortality and major adverse cardiac events increase as operator volumes decrease in PCI. Among studies showing a relationship, high-volume operators were defined variably, with annual PCIs ranging from >11 to >270, with no clear evidence of a threshold effect within the ranges studied.

Risk‐Treatment Paradox in the Selection of Transradial Access for Percutaneous Coronary Intervention

Background Access site complications contribute to morbidity and mortality during percutaneous coronary intervention (PCI). Transradial arterial access significantly lowers the risk of access site complications compared to transfemoral arteriotomy. We sought to develop a prediction model for access site complications in patients undergoing PCI with femoral arteriotomy, and assess whether transradial access was selectively used in patients at high risk for complications. Methods and Results We analyzed 17 509 patients who underwent PCI without circulatory support from 2008 to 2011 at 5 institutions. Transradial arterial access was used in 17.8% of patients. In those who underwent transfemoral access, 177 (1.2%) patients had access site complications. Using preprocedural clinical and demographic data, a prediction model for femoral arteriotomy complications was generated. The variables retained in the model included: elevated age (P<0.001), female gender (P<0.001), elevated troponin (P<0.001), decreased renal function or dialysis (P=0.002), emergent PCI (P=0.01), prior PCI (P=0.005), diabetes (P=0.008), and peripheral artery disease (P=0.003). The model showed moderate discrimination (optimism‐adjusted c‐statistic=0.72) and was internally validated via bootstrap resampling. Patients with higher predicted risk of complications via transfemoral access were less likely to receive transradial access (P<0.001). Similar results were seen in patients presenting with and without ST‐segment myocardial infarction and when adjusting for individual physician operator. Conclusions We generated and validated a model for transfemoral access site complications during PCI. Paradoxically, patients most likely to develop access site complications from transfemoral access, and therefore benefit from transradial access, were the least likely to receive transradial access.

Clinical Preventability of 30-Day Readmission After Percutaneous Coronary Intervention

Background Early readmission after PCI is an important contributor to healthcare expenditures and a target for performance measurement. The extent to which 30‐day readmissions after PCI are preventable is unknown yet essential to minimizing their occurrence. Methods and Results PCI patients readmitted to hospital at which PCI was performed within 30 days of discharge at the Massachusetts General Hospital and Brigham and Womens Hospital were identified, and their medical records were independently reviewed by 2 physicians. Each reviewer used an ordinal scale (0, not; 1, possibly; 2, probably; and 3, definitely preventable) to rate clinical preventability, and a total sum score ≥2 was considered preventable. Characteristics of preventable and unpreventable readmissions were compared, and predictors of clinical preventability were assessed by using multivariate logistic regression. Of 9288 PCIs performed, 9081 (97.8%) patients survived to initial hospital discharge and 1007 (11.1%) were readmitted to the index hospital within 30 days. After excluding repeat readmissions, 893 readmissions were reviewed. Fair agreement between physician reviewers was observed (weighted κ statistic 0.44 [95% CI 0.39 to 0.49]). After aggregation of scores, 380 (42.6%) readmissions were deemed preventable and 513 (57.4%) were deemed not preventable. Common causes of preventable readmissions included staged PCI without new symptoms (14.7%), vascular/bleeding complications of PCI (10.0%), and congestive heart failure (9.7%). Conclusions Nearly half of 30‐day readmissions after PCI may have been prevented by changes in clinical decision‐making. Focusing on these readmissions may reduce readmission rates.

Comparison of Transradial Versus Transfemoral Percutaneous Coronary Intervention in Routine Practice : Evidence for the Importance of “Falsification Hypotheses” in Observational Studies of Comparative Effectiveness

To the Editor: There has been growing interest in the use of the transradial approach for percutaneous coronary intervention (PCI), supported by randomized clinical trials involving experienced transradial operators [(1,2)][1]. However, the assessment of transradial PCI in routine practice has

The Clinical Significance of Continuous ECG (Ambulatory ECG or Holter) Monitoring of the ST-Segment to Evaluate Ischemia: A Review

Silent ischemia is a common manifestation of coronary artery disease (CAD). Continuous ECG (cECG) monitoring is an effective tool for assessing the frequency and duration of silent ischemic episodes for patients with CAD and for risk stratifying asymptomatic patients or those after an acute coronary syndrome by identifying those at increased risk for future cardiovascular events or death. cECG also allows monitoring of the effectiveness of therapy in patients with CAD. Treatment strategies targeted toward the elimination of silent ischemia have shown that revascularization was better than medical therapy in eliminating silent ischemia, but large scale, prospective studies targeting silent ischemia as a treatment endpoint are still lacking. Future research is warranted to study the effects of newer medical agents or the selected use of revascularization in those patients with persistent silent ischemia despite current medical regiments.

Anti-Anginal and Anti-Ischemic Effects of Late Sodium Current Inhibition

The effective treatment of coronary artery disease targets two distinct goals, controlling symptomatic angina and decreasing the adverse events associated with ischemia. Traditional anti-anginal and anti-ischemic drugs function by altering the determinants of myocardial oxygen supply or demand, usually by altering loading conditions, changing the heart rate, or impacting contractility. Blockade of the late inward sodium current, late INa, offers another target for the treatment of ischemia. Blockade of late INa reduces the sodium and calcium overload that follows ischemia. This improves myocardial relaxation and reduces left ventricular diastolic stiffness, in turn enhancing myocardial contractility and perfusion. Ranolazine, a late INa inhibitor, has been shown to provide both anti-anginal and anti-ischemic benefits without significant alterations in the heart rate and blood pressure in patients with stable coronary artery disease. When evaluated in patients with acute coronary syndrome, ranolazine has been shown to decrease recurrent ischemia, but not significantly reduce the risk of death or myocardial infarction. This review will address the rationale that inhibition of the late sodium current is beneficial in reducing cardiac dysfunction during ischemia, and discuss the clinical studies supporting the use of ranolazine for its anti-anginal and anti-ischemic effects.

Effectiveness of Arterial Closure Devices for Preventing Complications With Percutaneous Coronary Intervention

Background—Bleeding is associated with poor outcomes after percutaneous coronary intervention (PCI). Although arterial closure devices (ACDs) are widely used in clinical practice, whether they are effective in reducing bleeding complications during transfemoral PCI is uncertain. The objective of this study was to evaluate the effectiveness of ACDs for the prevention of vascular access site complications in patients undergoing transfemoral PCI using an instrumental variable approach. Methods and Results—We performed a retrospective analysis of the CathPCI Registry from 2009 to 2013 at 1470 sites across the United States. Variation in the proportion of ACDs used by each individual physician operator was used as an instrumental variable to address potential confounding. A 2-stage instrumental variable analysis was used as the primary approach. The main outcome measure was vascular access site complications, and nonaccess site bleeding was used as a falsification end point (negative control) to evaluate for potential confounding. A total of 1 053 155 ACDs were used during 2 056 585 PCIs during the study period. The vascular access site complication rate was 1.5%. In the instrumental variable analysis, the use of ACDs was associated with a 0.40% absolute risk reduction in vascular access site complications (95% confidence interval, 0.31–0.42; number needed to treat=250). Absolute differences in nonaccess site bleeding were negligible (risk difference, 0.04%; 95% confidence interval, 0.01–0.07), suggesting acceptable control of confounding in the comparison. Conclusions—ACDs are associated with a modest reduction in major bleeding after PCI. The number needed to treat with ACDs to prevent 1 major bleeding event is high.