Lymphedema Surveillance and Patient-Reported Anxiety: Comparison Between Volumetric Assessment and Bioimpedance Analysis.

Background: Lymphedema is a complication of breast cancer therapy associated with substantial anxiety. We designed a prospective, randomized study to assess the psychosocial impact of different surveillance methods for lymphedema. Methods and Results: In this open-label study of 38 women undergoing breast cancer surgery, we screened for lymphedema using traditional volumetric measurements (circumferential readings from the wrist to the axilla) versus bioimpedance spectroscopy (BIS) using electric current. The primary outcome measure was total anxiety measured by the Beck Anxiety Inventory, a 21-item questionnaire administered at preoperative, 6-week, 3-month, and 6-month postoperative visits (range 0-63 points). Outcome metrics were compared after adjustment for baseline anxiety. There were no differences in clinical characteristics or cancer therapies between groups, except for more reoperation for positive surgical margins in the BIS patients (5% vs. 32%, p = 0.036). Baseline anxiety, depression, and associated medical therapies were similar as well. Only one woman in each group developed lymphedema during the study. Anxiety was higher in the BIS group at baseline (mean Beck score 12.2 vs. 7.2, p < 0.001), but anxiety levels gradually declined by the end of the 6-month study in both groups, with no differences in adjusted anxiety scores between the two groups at any time point during follow-up (all p = NS). Conclusions: In this pilot study of women scheduled for breast cancer surgery, most subjects reported mild anxiety at baseline, and anxiety levels fell during continued lymphedema surveillance visits. There was no difference in patient-reported anxiety when surveillance was performed using standard volumetric versus BIS measurements.

Combining clinical and angiographic variables for estimating risk of target lesion revascularization after drug eluting stent placement.

BACKGROUND: Drug-eluting stents (DES) reduce restenosis but require prolonged antiplatelet therapy, when compared with bare metal stents. Ideally, the patient should be involved in this risk:benefit assessment prior to selecting DES, to maximize the benefits and cost-effectiveness of care, and to improve medication adherence. However, accurate estimation of restenosis risk may require angiographic factors identified at cardiac catheterization. METHODS: In a large PCI registry, we used logistic regression to identify clinical and angiographic predictors of clinically-driven target lesion revascularization (TLR) over the first year after stent placement. Discrimination c-statistic and integrated discrimination improvement (IDI) were used to calculate the incremental utility of angiographic variables when added to clinical predictors. RESULTS: Of 8501 PCI patients, TLR occurred in 4.5%. After adjusting for DES use, clinical TLR predictors were younger age, female sex, diabetes, prior PCI, and prior bypass surgery (model c-statistic 0.630). Angiographic predictors were vein graft PCI, in-stent restenosis lesion, longer stent length, and smaller stent diameter (c-statistic 0.650). After adding angiographic factors to the clinical model, c-statistic improved to 0.680 and the average separation in TLR risk among patients with and without TLR improved by 1% (IDI=0.010, 95% CI 0.009-0.014), primarily driven by those experiencing TLR (from 5.9% to 6.9% absolute risk). CONCLUSIONS: Among unselected PCI patients, the incidence of clinically-indicated TLR is <5% at 1-year, and standard clinical variables only moderately discriminate who will and will not experience TLR. Angiographic variables significantly improve TLR risk assessment, suggesting that stent selection may be best performed after coronary anatomy has been delineated. SHORT SUMMARY (FOR ANNOTATED TABLE OF CONTENTS): Although several recent studies have challenged traditional expectations regarding the duration of dual antiplatelet therapy, current guidelines recommend at least 6 to 12months of treatment after implantation of a drug eluting stent, with a shorter course for bare metal stents. Stent selection ideally should involve input from the patient receiving these stents, but multiple studies have suggested that angiographic factors - obtained after the patient has received sedation during the diagnostic catheterization - are important predictors of repeat revascularization. In this analysis from a large registry of patients receiving coronary stents, angiographic characteristics were found to significantly improve risk assessment for target lesion revascularization, when added to clinical variables alone.

Health Status Outcomes in Patients With Acute Myocardial Infarction After Rehospitalization.

BACKGROUND: Rehospitalizations after acute myocardial infarction for unplanned coronary revascularization and unstable angina (UA) are common. However, despite the inclusion of these events in composite end points of many clinical trials, their association with health status has not been studied. METHODS AND RESULTS: We included 3283 patients with acute myocardial infarction enrolled in a prospective, 24-center US study who had rehospitalizations independently classified by experienced cardiologists. Health status was assessed using Seattle Angina Questionnaire and EuroQol-5D Visual Analog Scale. In the propensity-matched cohorts, 1-year health status was compared between those who did and did not experience rehospitalization for UA or revascularization using a hierarchical linear model. Overall, mean age was 59 years, 33% were women, and 70% were white. Rehospitalization rates for UA and unplanned revascularization at 1 year were 4.3% and 4.7%. One-year Seattle Angina Questionnaire summary scores were worse in patients with rehospitalizations for UA (mean difference, -10.1; 95% confidence interval, -12.4 to -7.9) and unplanned revascularization (mean difference, -5.7; 95% confidence interval, -8.8 to -2.5) when compared with patients without such rehospitalizations. Similarly, EuroQol-5D Visual Analog Scale scores were worse among patients with such readmissions. Individual Seattle Angina Questionnaire domains indicated worse 1-year angina and quality of life outcomes among patients rehospitalized for UA or unplanned revascularization. CONCLUSIONS: Within the first year after acute myocardial infarction, rehospitalizations for UA and unplanned revascularization are associated with worse health status. These findings highlight the impact of such events from a patient's perspective, beyond their economic impact and support the use of UA and unplanned revascularization as elements of composite end points.

Discordant Aortic Valve Morphology in Monozygotic Twins: A Clinical Case Series.

IMPORTANCE: Bicuspid aortic valve (BAV) is considered an autosomal dominant condition, which is commonly associated with thoracic aortic aneurysm. Both conditions pose the risk of valvular and aortic complications not only for affected patients but also for genetically related persons as well. The genetic underpinnings of these disease processes, which are in various stages of elucidation, have implications for screening and risk prognostication. OBJECTIVE: To analyze genetic differences between 2 pairs of monozygotic twins that had discordant aortic valve morphology, with 1 twin in each pair having a BAV and the other having a trileaflet aortic valve. DESIGN, SETTING, AND PARTICIPANTS: Two pairs of twins that were objectively determined to be monozygotic were examined at a tertiary care medical center associated with an academic medical center. Aortic valves that were surgically excised for clinical indications were examined for morphology. Whole-exome sequencing was performed for the twin pair that had discordance of aortic valve and aortic aneurysm. In the second pair, targeted gene sequencing of 25 genes known to be associated with BAV and/or thoracic aortic aneurysm was performed. In each pair, the twin with a BAV underwent surgical aortic valve replacement for clinical indications. MAIN OUTCOMES AND MEASURES: Genetic coding variations between monozygotic twins using whole-exome sequencing and targeted gene sequencing. RESULTS: This case series included 2 pairs of male monozygotic twins; one pair was aged 51 years and the other aged 59 years. Genetic sequencing methods identified no pathogenic sequence changes between the twins in each pair. CONCLUSIONS AND RELEVANCE: Our findings challenge the traditional view of BAV as a condition with an entirely autosomal dominant inheritance pattern and emphasize the variability of penetrance of both BAV and thoracic aortic aneurysm as well as the variability of the association of the 2 conditions. Continued work to elucidate the genetic basis may lead to the refinement of risk stratification for affected patients and relatives.

Training the next generation of invasive cardiologists: Feasibility of implementing a trans-radial access program at an academic hospital.

BACKGROUND: Slow adoption of trans-radial access (TRA) for left heart catheterization (LHC) in the U.S. may be related to concerns about procedural complexity and a steep learning curve. However, TRA acceptance among novice operators remains poorly characterized. METHODS: We initiated a 1-year TRA learning period among lower-risk outpatients, followed by a "radial-first" policy for all LHC patients beginning year 2. By year 3, all fellows prospectively collected diagnostic LHC data as part of a quality improvement study. TRA procedural characteristics were compared with patients undergoing trans-femoral access for the 3months prior to the TRA program, and trends over time were evaluated. RESULTS: Between 7/2009 and 6/2012, we identified 960 patients undergoing LHC via TRA by 23 rotating cardiology fellows supervised by 5 interventional cardiologists. When evaluated against the 160 trans-femoral comparator patients, TRA patients had lower procedural success through the initial access site (88% vs. 99%, p<0.001) and longer fluoroscopy times (9.5 [5.8-15.9] vs. 6.5 [3.1-12.7] min, p<0.001), with similar contrast volumes and fewer catheters used. Despite tackling more complex patients during years 2-3, there were improvements in fluoroscopy times, catheter utilization, contrast volumes, and procedural success rates over time (all p<0.001). CONCLUSIONS: The dedicated adoption of TRA by an academic catheterization laboratory demonstrated improvements in efficiency and resource utilization over a relatively short period of time. Additional exposure to TRA during training may help facilitate acceptance of this approach among the next generation of invasive cardiologists. SHORT SUMMARY (FOR ANNOTATED TABLE OF CONTENTS): When initiating a trans-radial access program for cardiac catheterization at an academic training hospital, procedural success rates were lower and fluoroscopy times were higher than traditional trans-femoral access. Nonetheless, other procedural variables were similar between the 2 approaches, and improvements over time were consistent with the learning curves reported among experienced cardiologists in prior studies. Exposure to trans-radial access during training may help facilitate acceptance of this approach among the next generation of invasive cardiologists.

Ischemic Stroke with Troponin Elevation: Patient Characteristics, Resource Utilization, and In-Hospital Outcomes.

BACKGROUND: Among patients hospitalized for acute ischemic stroke, abnormal serum troponins are associated with higher risk of short-term mortality. However, most findings have been reported from European hospitals. Whether troponin elevation after stroke is independently associated with death among a more heterogeneous US population remains unclear. Furthermore, only a few studies have evaluated the association between the magnitude of troponin elevation and subsequent mortality, patterns of dynamic troponin changes over time, or whether troponin elevation is related to specific causes of death. METHODS: Using data collected in the American Heart Association's 'Get With The Guidelines' stroke registry between 2008 and 2012 at a tertiary care US hospital, we used logistic regression to evaluate the independent relationship between troponin elevation and mortality after adjusting for demographic and clinical characteristics. We then assessed whether the magnitude of troponin elevation was related to in-hospital mortality by calculating mortality rates according to tertiles of peak troponin levels. Dynamic troponin changes over time were evaluated as well. To better understand whether troponin elevation identified patients most likely to die due to a specific cause of death, investigators blinded from troponin values reviewed all in-hospital deaths, and the association between troponin elevation and mortality was evaluated among patients with cardiac, neurologic, or other causes of death. RESULTS: Of 1,145 ischemic stroke patients, 199 (17%) had elevated troponin levels. Troponin-positive patients had more cardiovascular risk factors, more intensive medical therapy, and greater use of cardiac procedures. These individuals had higher in-hospital mortality rates than troponin-negative patients (27 vs. 8%, p < 0.001), and this association persisted after adjustment for 13 clinical and management variables (OR 4.28, 95% CI 2.40-7.63). Any troponin elevation was associated with higher mortality, even at very low peak troponin levels (mortality rates 24-29% across tertiles of troponin). Patients with persistently rising troponin levels had fewer anticoagulant and antiatherosclerotic therapies, with markedly worse outcomes. Furthermore, troponin-positive patients had higher rates of all categories of death: neurologic (17 vs. 7%), cardiac (5 vs. <1%), and other causes of death (5 vs. <1%; p < 0.001 for all comparisons). CONCLUSIONS: Ischemic stroke patients with abnormal troponin levels are at higher risk of in-hospital death, even after accounting for demographic and clinical characteristics, and any degree of troponin elevation identifies this higher level of risk. Troponins that continue to rise during the hospitalization identify stroke patients at markedly higher risk of mortality, and both neurologic and non-neurologically mediated mortality rates are higher when troponin is elevated.

Predicting Adverse Outcomes After Myocardial Infarction Among Patients With Diabetes Mellitus.

BACKGROUND: Although patients with diabetes mellitus experience high rates of adverse events after acute myocardial infarction (AMI), including death and recurrent ischemia, some diabetic patients are likely at low risk, whereas others are at high risk. We sought to develop prediction models to stratify risk after AMI in patients with diabetes mellitus. METHODS AND RESULTS: We developed prediction models for long-term mortality and angina among 1613 patients with diabetes mellitus discharged alive after AMI from 24 US hospitals and then validated the models in a separate, multicenter registry of 786 patients with diabetes mellitus. Event rates in the derivation cohort were 27% for 5-year mortality and 27% for 1-year angina. Parsimonious prediction models demonstrated good discrimination (c-indices=0.78 and 0.69, respectively) and excellent calibration. Within the context of the predictors we estimated, the strongest predictors for mortality were higher creatinine, not working at the time of the AMI, older age, lower hemoglobin, left ventricular dysfunction, and chronic heart failure. The strongest predictors for angina were angina burden in the 4 weeks before the AMI, younger age, history of prior coronary bypass graft surgery, and non-white race. The lowest and highest deciles of predicted risk ranged from 4% to 80% for mortality and 12% to 59% for angina. The models also performed well in external validation (c-indices=0.78 and 0.73, respectively). CONCLUSIONS: We found a wide range of risk for adverse outcomes after AMI in diabetic patients. Predictive models can identify patients with diabetes mellitus for whom closer follow-up and aggressive secondary prevention strategies should be considered.

Recurrent Takotsubo Cardiomyopathy Related to Recurrent Thyrotoxicosis.

Takotsubo cardiomyopathy, or transient left ventricular apical ballooning syndrome, is characterized by acute left ventricular dysfunction caused by transient wall-motion abnormalities of the left ventricular apex and mid ventricle in the absence of obstructive coronary artery disease. Recurrent episodes are rare but have been reported, and several cases of takotsubo cardiomyopathy have been described in the presence of hyperthyroidism. We report the case of a 55-year-old woman who had recurrent takotsubo cardiomyopathy, documented by repeat coronary angiography and evaluations of left ventricular function, in the presence of recurrent hyperthyroidism related to Graves disease. After both episodes, the patient's left ventricular function returned to normal when her thyroid function normalized. These findings suggest a possible role of thyroid-hormone excess in the pathophysiology of some patients who have takotsubo cardiomyopathy.

Relationship between stent type and quality of life after percutaneous coronary intervention for acute myocardial infarction.

BACKGROUND: Drug-eluting stents (DES) reduce restenosis, as compared with bare-metal stents (BMS); however, the relationship between stent type and health status is unknown. We examined whether stent type was associated with health status outcomes in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: We evaluated 6- and 12-month health status in 2,694 patients with acute myocardial infarction (AMI) enrolled in the TRIUMPH and PREMIER registries who underwent PCI with DES (n = 1,361) or BMS (n = 1,333). Health status was assessed with the Seattle Angina Questionnaire, Medical Outcomes Study Short Form-12, and Patient Health Questionnaire depression scale. Propensity matching was performed to account for baseline differences in patient characteristics, resulting in a comparison cohort of 784 patients treated with DES and 784 patients treated with BMS. Both groups experienced significant improvements in health status at 6 and 12 months after PCI. Drug-eluting stent use was associated with a small improvement in Seattle Angina Questionnaire quality of life and functional limitation scores at 6 months (3.6 [95% CI 0.96-6.21], P = .007, and 3.8 [1.55-6.01], P < .001, respectively), but not at 12 months (2.3 [-0.46 to 5.03], P = .10, and 0.3 [-2.04 to 2.48], P = .85, respectively). CONCLUSIONS: In patients with AMI undergoing PCI, DES use was associated with transient but unsustained health status benefits over 12 months after AMI.

Use of a Vascular Sheath in the Axillary Artery as an Alternative Access Approach for Placing an Impella 5.0 Device.

Many patients who are in cardiogenic shock need mechanical support for clinical stabilization after acute insults such as myocardial infarction. However, the placement of advanced devices can be hindered by anatomic constraints or the physiologic sequelae of shock, as we describe in this report. A 67-year-old woman with prior coronary artery bypass grafting and extensive chest-wall scarring from previous defibrillator implantations presented with myocardial infarction and refractory cardiogenic shock. The patient's vascular anatomy and prior surgery precluded conventional percutaneous implantation of an Impella 5.0 ventricular support device. We delivered the Impella device through the patient's tortuous, vasoconstricted axillary artery with use of a vascular sheath and other percutaneous techniques. The success of this approach suggests that combining the expertise of cardiologists and cardiovascular surgeons can improve the outcomes of patients with complex anatomic issues.

Pooled comparison of regadenoson versus adenosine for measuring fractional flow reserve and coronary flow in the catheterization laboratory.

BACKGROUND: Adenosine is the gold standard for augmenting coronary flow during fractional flow reserve (FFR) testing of intermediate coronary stenoses. However, intravenous infusion is time-consuming and intracoronary injection is subject to variability. Regadenoson is a newer adenosine alternative administered as a single intravenous bolus during nuclear stress testing, but its efficacy and safety during FFR testing have been evaluated only in small, single-center studies. METHODS: We pooled data from 5 academic hospitals, in which patients undergoing clinically-indicated FFR prospectively underwent comparison of intravenous adenosine infusion (140-175mcg/kg/min) versus regadenoson bolus (400mcg). Hemodynamics and symptoms with adenosine were recorded until maximal hyperemia occurred, and after returning to baseline hemodynamics, regadenoson was administered and monitoring was repeated. In a subset of patients with coronary flow data, average peak velocity (APV) at the distal flow sensor was recorded. RESULTS: Of 149 patients enrolled, mean age was 59±9years, 76% were male, and 54% underwent testing of the left anterior descending artery. Mean adenosine-FFR and regadenoson-FFR were identical (0.82±0.10) with excellent correlation of individual values (r=0.96, p<0.001) and no difference in patient-reported symptoms. Four patients (2.6%) had discrepancies between the 2 drugs for the clinical decision-making cutoff of FFR≤0.80. Coronary flow responses to adenosine and regadenoson were similar (APV at maximal hyperemia 36cm/s for both, p=0.81). CONCLUSIONS: Regadenoson single-bolus administration has comparable FFR, symptoms, and coronary flow augmentation when compared with standard intravenous adenosine infusion. With its greater ease of administration, regadenoson may be a more "user-friendly" option for invasive ischemic testing.

Intensive care units with low versus high volume of myocardial infarction: clinical outcomes, resource utilization, and quality metrics.

BACKGROUND: The volume-outcome relationship associated with intensive care unit (ICU) experience with managing acute myocardial infarction (AMI) remains inadequately understood. METHODS AND RESULTS: Within a multicenter clinical ICU database, we identified patients with a primary ICU admission diagnosis of AMI between 2008 and 2010 to evaluate whether annual AMI volume of an individual ICU is associated with mortality, length-of-stay, or quality indicators. Patients were categorized into those treated in ICUs with low-annual-AMI volume (≤50th percentile, <2 AMI patients/month, n=569 patients) versus high-annual-AMI volume (≥90th percentile, ≥8 AMI patients/month, n=17 553 patients). Poisson regression and generalized estimating equation with negative binomial regression were used to calculate the relative risk (95% CI) for mortality and length-of-stay, respectively, associated with admission to a low-AMI-volume ICU. When compared with high-AMI-volume, patients admitted to low-AMI-volume ICUs had substantially more medical comorbidities, higher in-hospital mortality (11% versus 4%, P<0.001), longer hospitalizations (6.9±7.0 versus 5.0±5.0 days, P<0.001), and fewer evidence-based therapies for AMI (reperfusion therapy, antiplatelets, ß-blockers, and statins). However, after adjustment for baseline patient characteristics, low-AMI-volume ICU was no longer an independent predictor of in-hospital mortality (relative risk 1.17 [0.87 to 1.56]) or hospital length-of-stay (relative risk 1.01 [0.94 to 1.08]). Similar findings were noted in secondary analyses of ICU mortality and ICU length-of-stay. CONCLUSIONS: Admission to an ICU with lower annual AMI volume is associated with higher in-hospital mortality, longer hospitalization, and lower use of evidence-based therapies for AMI. However, the relationship between low-AMI-volume and outcomes is no longer present after accounting for the higher-risk medical comorbidities and clinical characteristics of patients admitted to these ICUs.

Recognition of incident diabetes mellitus during an acute myocardial infarction.

BACKGROUND: Diabetes mellitus (DM) is common in patients hospitalized with an acute myocardial infarction (AMI), representing in some cases the first opportunity to recognize and treat DM. We report the incidence of new DM and its recognition among patients with AMI. METHODS AND RESULTS: Patients in a 24-site US AMI registry (2005-08) had glycosylated hemoglobin assessed at a core laboratory, with results blinded to clinicians and local clinical measurements left to the discretion of the treating providers. Among 2854 AMI patients without known DM on admission, 287 patients (10%) met criteria for previously unknown DM, defined by a core laboratory glycosylated hemoglobin of ≥6.5%. Among these, 186 (65%) were unrecognized by treating clinicians, receiving neither DM education, glucose-lowering medications at discharge, nor documentation of DM in the chart (median glycosylated hemoglobin of unrecognized patients, 6.7%; range, 6.5-12.3%). Six months after discharge, only 5% of those not recognized as having DM during hospitalization had been initiated on glucose-lowering medications versus 66% of those recognized (P<0.001). CONCLUSIONS: Underlying DM that has not been previously diagnosed is common among AMI patients, affecting 1 in 10 patients, yet is recognized by the care team only one third of the time. Given its frequency and therapeutic implications, including but extending beyond the initiation of glucose-lowering treatment, consideration should be given to screening all AMI patients for DM during hospitalization. Inexpensive, ubiquitous, and endorsed as an acceptable screen for DM, glycosylated hemoglobin testing should be considered for this purpose.

Longitudinal persistence with secondary prevention therapies relative to patient risk after myocardial infarction.

BACKGROUND: Prior studies have demonstrated that patients with high-risk acute myocardial infarction (AMI) are less likely to receive guideline-directed medications during hospitalisation. It is unknown if this paradox persists following discharge. We aimed to assess if persistence with guideline-directed medications post discharge varies by patients' risk following AMI. METHODS: Data were analysed from two prospective, multicentre US AMI registries. The primary outcome was persistence with all prescribed guideline-directed medications (aspirin, ß-blockers, statins, angiotensin-antagonists) at 1, 6 and 12 months post discharge. The association between risk and medication persistence post discharge was assessed using multivariable mixed-effect models. RESULTS: Among 6434 patients with AMI discharged home, 2824 were considered low-risk, 2014 intermediate-risk and 1596 high-risk for death based upon their Global Registry of Acute Coronary Event (GRACE) 6-month risk score. High-risk was associated with a lower likelihood of receiving all appropriate therapies at discharge compared with low-risk patients (relative risk (RR) 0.90; 95% CI 0.87 to 0.94). At 12 months, the rate of persistence with all prescribed therapies was 61.5%, 57.9% and 45.9% among low-risk, intermediate-risk and high-risk patients, respectively. After multivariable adjustment, high-risk was associated with lower persistence with all prescribed medications (RR 0.87; 95% CI 0.82 to 0.92) over follow-up. Similar associations were seen for individual medications. Over the 5 years of the study, persistence with prescribed therapies post discharge improved modestly among high-risk patients (RR 1.05; 95% CI 1.03 to 1.08 per year). CONCLUSIONS: High-risk patients with AMI have a lower likelihood of persistently taking prescribed medications post discharge as compared with low-risk patients. Continued efforts are needed to improve the use of guideline-directed medications in high-risk patients.

Risk factors for rehospitalization for acute coronary syndromes and unplanned revascularization following acute myocardial infarction.

BACKGROUND: Rehospitalizations for acute coronary syndromes (ACS) and coronary revascularization after an acute myocardial infarction (AMI) are not only common and costly but can also impact patients' quality of life. In contrast to mortality and all-cause readmissions, little insight is available into risk factors associated with ACS and revascularization after AMI. METHODS AND RESULTS: In a multicenter AMI registry, we examined the rates and predictors of rehospitalizations for ACS and revascularization within the year after AMI among 3283 patients. Staged revascularization procedures were excluded. Kaplan-Meier estimated rates of rehospitalization due to ACS and revascularization were 6.8% and 4.1%, respectively. In hierarchical, multivariable models, the strongest predictors of rehospitalization for ACS were coronary artery bypass graft prior to AMI hospitalization (hazard ratio [HR] 2.12, 95% CI 1.45 to 3.10), female sex (HR 1.67, 95% CI 1.23 to 2.25), and in-hospital PCI (HR 1.85, 95% CI 1.28 to 2.69). The strongest predictors of subsequent revascularization were multivessel disease (HR 2.89, 95% CI 1.90 to 4.39) and in-hospital percutaneous coronary intervention with a bare metal stent (HR 2.08, 95% CI 1.19 to 3.63). The Global Registry of Acute Coronary Events mortality risk score was not associated with the risk of rehospitalization for ACS or revascularization. CONCLUSIONS: Unique characteristics are associated with admissions for ACS and revascularization, as compared with survival. These multivariable risk predictors may help identify patients at high risk for ACS and revascularization, in whom intensification of secondary prevention therapies or closer post-AMI follow-up may be warranted.

The reliability of in-hospital diagnoses of diabetes mellitus in the setting of an acute myocardial infarction.

OBJECTIVE: Incident diabetes mellitus (DM) is important to recognize in patients with acute myocardial infarction (AMI). To develop an efficient screening strategy, we explored the use of random plasma glucose (RPG) at admission and fasting plasma glucose (FPG) to select patients with AMI for glycosylated hemoglobin (HbA1c) testing. DESIGN SETTING ANDPARTICIPANTS: Prospective registry of 1574 patients with AMI not taking glucose-lowering medication from 24 US hospitals. All patients had HbA1c measured at a core laboratory and admission RPG and ≥2 FPGs recorded during hospitalization. We examined potential combinations of RPG and FPG and compared these with HbA1c≥6.5%-considered the gold standard for DM diagnosis in these analyses. RESULTS: An RPG>140 mg/dL or FPG≥126 mg/dL had high sensitivity for DM diagnosis. Combining these into a screening protocol (if admission RPG>140, check HbA1c; or if FPG≥126 on a subsequent day, check HbA1c) led to HbA1c testing in 50% of patients and identified 86% with incident DM (number needed to screen (NNS)=3.3 to identify 1 case of DM; vs NNS=5.6 with universal HbA1c screening). Alternatively, using an RPG>180 led to HbA1c testing in 40% of patients with AMI and identified 82% of DM (NNS=2.7). CONCLUSIONS: We have established two potential selective screening methods for DM in the setting of AMI that could identify the vast majority of incident DM by targeted screening of 40-50% of patients with AMI with HbA1c testing. Using these methods may efficiently identify patients with AMI with DM so that appropriate education and treatment can be promptly initiated.

Rethinking composite end points in clinical trials: insights from patients and trialists.

BACKGROUND: Many clinical trials use composite end points to reduce sample size, but the relative importance of each individual end point within the composite may differ between patients and researchers. METHODS AND RESULTS: We asked 785 cardiovascular patients and 164 clinical trial authors to assign 25 "spending weights" across 5 common adverse events comprising composite end points in cardiovascular trials: death, myocardial infarction, stroke, coronary revascularization, and hospitalization for angina. We then calculated end point ratios for each participant's ratings of each nonfatal end point relative to death. Whereas patients assigned an average weight of 5 to death, equal or greater weight was assigned to myocardial infarction (mean ratio, 1.12) and stroke (ratio, 1.08). In contrast, clinical trialists were much more concerned about death (average weight, 8) than myocardial infarction (ratio, 0.63) or stroke (ratio, 0.53). Both patients and trialists considered revascularization (ratio, 0.48 and 0.20, respectively) and hospitalization (ratio, 0.28 and 0.13, respectively) as substantially less severe than death. Differences between patient and trialist end point weights persisted after adjustment for demographic and clinical characteristics (P<0.001 for all comparisons). CONCLUSIONS: Patients and clinical trialists did not weigh individual components of a composite end point equally. Whereas trialists are most concerned about avoiding death, patients place equal or greater importance on reducing myocardial infarction or stroke. Both groups considered revascularization and hospitalization as substantially less severe. These findings suggest that equal weights in a composite clinical end point do not accurately reflect the preferences of either patients or trialists.

Incremental utility of iodine-123 meta-iodobenzylguanidine imaging beyond established heart failure risk models.

BACKGROUND: Nuclear myocardial imaging with iodine-123 meta-iodobenzylguanidine ((123)I-mIBG) is approved for risk stratification of patients with systolic heart failure (HF). Whether (123)I-mIBG imaging provides incremental prognostic utility beyond established risk models remains unclear. METHODS AND RESULTS: In a multicenter study, 961 patients with moderate systolic HF underwent (123)I-mIBG imaging and were followed for cardiac death, progressive HF, or life-threatening arrhythmias over 2 years. We constructed 4 multivariable models, using variables from each of 4 published HF risk models, and patient-level scores were calculated both before and after adding the heart-to-mediastinum ratio (H/M) from (123)I-mIBG imaging. Incremental utility was evaluated by calculating integrated discrimination improvement (IDI), which quantifies the increase in probability of experiencing the primary end point after adding H/M to each model. The composite end point occurred in 25% of patients. After adding H/M, absolute IDI ranged from 2.1% to 3.0%, representing 33%-59% relative improvements in risk stratification. Of note, hazard ratios for H/M were remarkably similar between risk models (0.40-0.44 for predicting the composite end point, 0.10-0.18 for mortality; all P < .001). CONCLUSIONS: Despite notable differences in predictor variables, patient populations, and analytic techniques from which each model was initially derived, adding (123)I-mIBG data to HF risk models consistently identified patients at lower risk of experiencing adverse events.