Left atrial cross-sectional area is a novel measure of atrial shape associated with cardioembolic strokes.

OBJECTIVE: Cardioembolic (CE) stroke carries significant morbidity and mortality. Left atrial (LA) size has been associated with CE risk. We hypothesised that differential LA remodelling impacts on pathophysiological mechanism of major CE strokes. METHODS: A cohort of consecutive patients hospitalised with ischaemic stroke, classified into CE versus non-CE strokes using the Causative Classification System for Ischaemic Stroke were enrolled. LA shape and remodelling was characterised by assessing differences in maximal LA cross-sectional area (LA-CSA) in a cohort of 40 prospectively recruited patients with ischaemic stroke using three-dimensional (3D) echocardiography. Flow velocity profiles were measured in spherical versus ellipsoidal in vitro models to determine if LA shape influences flow dynamics. Two-dimensional (2D) LA-CSA was subsequently derived from standard echocardiographic views and compared with 3D LA-CSA. RESULTS: A total of 1023 patients with ischaemic stroke were included, 230 (22.5%) of them were classified as major CE. The mean age was 68±16 years, and 464 (45%) were women. The 2D calculated LA-CSA correlated strongly with the LA-CSA measured by 3D in both end-systole and end-diastole. In vitro flow models showed shape-related differences in mid-level flow velocity profiles. Increased LA-CSA was associated with major CE stroke (adjusted relative risk 1.10, 95% CI 1.04 to 1.16; p<0.001), independent of age, gender, atrial fibrillation, left ventricular ejection fraction and CHA2DS2-VASc score. Specifically, the inclusion of LA-CSA in a model with traditional risk factors for CE stroke resulted in significant improvement in model performance with the net reclassification improvement of 0.346 (95% CI 0.189 to 0.501; p=0.00001) and the integrated discrimination improvement of 0.013 (95% CI 0.003 to 0.024; p=0.0119). CONCLUSIONS: LA-CSA is a marker of adverse LA shape associated with CE stroke, reflecting importance of differential LA remodelling, not simply LA size, in the mechanism of CE risk.

Comparison of 30-Day Readmission Rates After Hospitalization for Acute Myocardial Infarction in Men Versus Women.

Readmission after hospitalization for acute myocardial infarction (AMI) significantly contributes to preventable morbidity and health-care costs. Outcomes after AMI vary by sex but the relationship of sex to readmissions warrants further exploration. Using the 2013 Nationwide Readmissions Database, we identified patients with a principal discharge diagnosis of AMI and stratified all-cause 30-day readmissions by sex and age. Of 214,824 patients, 44% were 18 to 64 years of age, 56% were ≥65 years, and 28% and 45%, respectively, were female. For patients 18 to 64 years, the readmission rate was 14% for women and 10% for men (p <0.001). For patients ≥65 years, the readmission rate was 18% for women and 16% for men (p <0.001). After adjusting for co-morbidities, women had a significantly higher risk of 30-day readmission compared with men, an effect that was strongest in younger women (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.06 to 1.39, for ages 18 to 44; OR 1.13, 95% CI 1.07 to 1.18, for ages 45 to 64; OR 1.13, 95% CI 1.07 to 1.19, for ages 65 to 74, interaction p <0.001). The procedure rates during the index hospitalization were significantly lower for women. The most common readmission diagnoses were recurrent AMI, ischemic heart disease, and heart failure. Costs associated with readmissions after AMI totaled $447,506,740, of which $176,743,622 were attributed to readmissions of women. In conclusion, women are at higher risk of short-term readmission after an AMI hospitalization than men, particularly younger women. Sex-specific strategies to reduce these readmissions may be warranted.

Angina Severity, Depression, and Response to Percutaneous Revascularization in Patients With Chronic Total Occlusion of Coronary Arteries.

OBJECTIVES: This study sought to quantify depression rates in patients referred for percutaneous coronary intervention (PCI) for chronic total occlusion (CTO), assess its relationship to baseline angina symptoms, and compare angina improvement after CTO-PCI between depressed and non-depressed patients. BACKGROUND: Depression is common among patients with chronic angina, and portends poor prognosis. CTOs are a common cause of angina. The relationships between angina, depression, and CTO intervention are unknown. METHODS: We collected baseline and 30-day post-PCI data on angina (Seattle Angina Questionnaire [SAQ7]), dyspnea (Rose Dyspnea Scale [RDS]), and depression status (Patient Health Questionnaire [PHQ-2]) on 45 consecutive patients referred for CTO-PCI between October 2013 and October 2014. RESULTS: Depression (PHQ-2 score ≥3) was present in 18/45 patients (40%) at baseline. Baseline SAQ7 Summary and SAQ7 Angina Frequency scores for depressed patients were 35.4 (range, 28.4-42.4) and 54.4 (range, 43.0-65.8), compared with 67.3 (range, 57.5-77.1) and 77.8 (range, 68.5-87.1) for non-depressed patients (P<.001 and P=.01, respectively). Following CTO-PCI, the mean improvement in SAQ7 Summary and SAQ7 Angina Frequency scores was 48.5 (range, 35.4-61.5) and 32.8 (range, 21.0-44.5) for patients with depression, compared with 16.5 (range, 5.87-27.2) and 12.6 (range, 3.0-22.2) for patients without depression (P<.001 and P=.01, respectively). Following PCI, the presence of depression was reduced (72% relative reduction vs. baseline; P=.01). CONCLUSIONS: Depression identifies patients more limited by angina and more likely to respond to CTO-PCI compared with non-depressed patients. Depression screening may be indicated for patients with CTO, as 67% of CTO patients were not receiving treatment for depression.

Feasibility of a Tablet Computer System to Collect Patient-reported Symptom Severity in Patients Undergoing Diagnostic Coronary Angiography.

BACKGROUND: Percutaneous coronary intervention is the most commonly performed revascularization modality for chronic stable angina, but does not improve survival or reduce major adverse cardiovascular event. Percutaneous coronary intervention in this population is performed primarily for symptomatic benefit; therefore, symptom reduction is an important marker of quality. Patient-reported outcome measures (PROMs) have been developed for chest pain and dyspnea which are valid and responsive to treatment; however, they are not widely used in routine care. We present a model for use of PROMs in routine care. METHODS: Partners Health System funded a tablet computer software platform to collect PROMs and include them in the medical record. We implemented this platform in the catheterization laboratory at Massachusetts General Hospital, targeting patients presenting for coronary angiography. Patients are assessed using the SAQ-7, the Rose dyspnea scale, the PHQ-2, and the PROMIS-10. We used a phased implementation, with the final program including preprocedure measurement, presentation of data to clinical providers, and follow up using an email platform. RESULTS: We successfully captured measures from 474 patients, 53.5% of outpatient visits. Key success factors included high-level leadership support and resources, a user-friendly interface for patients and staff, easily interpretable measures, and clinical relevance. CONCLUSIONS: We have demonstrated that routine capture of patient-reported symptom severity is technically feasible in a real-world care environment. We share our experiences to provide others with a model for similar programs, and to accelerate implementation nationwide by helping others avoid pitfalls. We believe expansion of similar programs nationally may lead to more robust quality infrastructure.

Predicting the Presence of an Acute Coronary Lesion Among Patients Resuscitated From Cardiac Arrest.

BACKGROUND: A mechanism to stratify patients resuscitated from a cardiac arrest according to the likelihood of an acute coronary lesion would have significant utility. We thus sought to develop and validate a risk prediction model for the presence of an acute coronary lesion among patients resuscitated from an arrest. METHODS AND RESULTS: All subjects undergoing coronary angiography after resuscitation from a cardiac arrest were identified in an ongoing institutional registry from 2009 to 2014. Backwards stepwise selection of candidate covariates was used to create a logistic regression model for the presence of an angiographic culprit lesion and internally validated with bootstrapping. A clinical point score was generated and its prognostic abilities compared with contemporary measures. Among 247 subjects undergoing coronary angiography after resuscitation from a cardiac arrest, 130 (52%) had an acute lesion in a coronary artery. A multivariable model-including angina, congestive heart failure symptoms, shockable arrest rhythm (ventricular fibrillation/ventricular tachycardia), and ST-elevations-had excellent discrimination (optimism corrected C-Statistic, 0.88) and calibration (Hosmer-Lemeshow P=0.540) for an acute coronary lesion. Compared with electrocardiographic findings alone, a point score based on this model more accurately predicted the presence of an acute lesion among patients resuscitated from a cardiac arrest (integrated discrimination improvement, 0.10; 95% confidence interval, 0.04-0.19; P<0.001). CONCLUSIONS: Patients with a cardiac arrest can be risk stratified for the presence of an acute coronary lesion using 4 easily measured variables. This simple risk score may be used to improve patient selection for emergent coronary angiography among resuscitated patients.

Enhancing the Prediction of 30-Day Readmission After Percutaneous Coronary Intervention Using Data Extracted by Querying of the Electronic Health Record.

BACKGROUND: Early readmission after percutaneous coronary intervention is an important quality metric, but prediction models from registry data have only moderate discrimination. We aimed to improve ability to predict 30-day readmission after percutaneous coronary intervention from a previously validated registry-based model. METHODS AND RESULTS: We matched readmitted to non-readmitted patients in a 1:2 ratio by risk of readmission, and extracted unstructured and unconventional structured data from the electronic medical record, including need for medical interpretation, albumin level, medical nonadherence, previous number of emergency department visits, atrial fibrillation/flutter, syncope/presyncope, end-stage liver disease, malignancy, and anxiety. We assessed differences in rates of these conditions between cases/controls, and estimated their independent association with 30-day readmission using logistic regression conditional on matched groups. Among 9288 percutaneous coronary interventions, we matched 888 readmitted with 1776 non-readmitted patients. In univariate analysis, cases and controls were significantly different with respect to interpreter (7.9% for cases and 5.3% for controls; P=0.009), emergency department visits (1.12 for cases and 0.77 for controls; P<0.001), homelessness (3.2% for cases and 1.6% for controls; P=0.007), anticoagulation (33.9% for cases and 22.1% for controls; P<0.001), atrial fibrillation/flutter (32.7% for cases and 28.9% for controls; P=0.045), presyncope/syncope (27.8% for cases and 21.3% for controls; P<0.001), and anxiety (69.4% for cases and 62.4% for controls; P<0.001). Anticoagulation, emergency department visits, and anxiety were independently associated with readmission. CONCLUSIONS: Patient characteristics derived from review of the electronic health record can be used to refine risk prediction for hospital readmission after percutaneous coronary intervention.

Association between public reporting of outcomes with procedural management and mortality for patients with acute myocardial infarction.

BACKGROUND: Public reporting of procedural outcomes may create disincentives to provide percutaneous coronary intervention (PCI) for critically ill patients. OBJECTIVES: This study evaluated the association between public reporting with procedural management and outcomes among patients with acute myocardial infarction (AMI). METHODS: Using the Nationwide Inpatient Sample, we identified all patients with a primary diagnosis of AMI in states with public reporting (Massachusetts and New York) and regionally comparable states without public reporting (Connecticut, Maine, Maryland, New Hampshire, Rhode Island, and Vermont) between 2005 and 2011. Procedural management and in-hospital outcomes were stratified by public reporting. RESULTS: Among 84,121 patients hospitalized with AMI, 57,629 (69%) underwent treatment in a public reporting state. After multivariate adjustment, percutaneous revascularization was performed less often in public reporting states than in nonreporting states (odds ratio [OR]: 0.81, 95% confidence interval [CI]: 0.67 to 0.96), especially among older patients (OR: 0.75, 95% CI: 0.62 to 0.91), those with Medicare insurance (OR: 0.75, 95% CI: 0.62 to 0.91), and those presenting with ST-segment elevation myocardial infarction (OR: 0.63, 95% CI: 0.56 to 0.71) or concomitant cardiac arrest or cardiogenic shock (OR: 0.58, 95% CI: 0.47 to 0.70). Overall, patients with AMI in public reporting states had higher adjusted in-hospital mortality rates (OR: 1.21, 95% CI: 1.06 to 1.37) than those in nonreporting states. This was observed predominantly in patients who did not receive percutaneous revascularization in public reporting states (adjusted OR: 1.30, 95% CI: 1.13 to 1.50), whereas those undergoing the procedure had lower mortality (OR: 0.71, 95% CI: 0.62 to 0.83). CONCLUSIONS: Public reporting is associated with reduced percutaneous revascularization and increased in-hospital mortality among patients with AMI, particularly among patients not selected for PCI.

Surgical ineligibility and mortality among patients with unprotected left main or multivessel coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: Decisions to proceed with surgical versus percutaneous revascularization for multivessel coronary artery disease are often based on subtle clinical information that may not be captured in contemporary registries. The present study sought to evaluate the association between surgical ineligibility documented in the medical record and long-term mortality among patients with unprotected left main or multivessel coronary artery disease undergoing percutaneous coronary intervention. METHODS AND RESULTS: All subjects undergoing nonemergent percutaneous coronary intervention for unprotected left main or multivessel coronary artery disease were identified at 2 academic medical centers from 2009 to 2012. Documentation of surgical ineligibility was assessed through review of electronic medical records. Cox proportional hazard models adjusted for known mortality risk factors were created to assess long-term mortality in patients with and without documentation of surgical ineligibility. Among 1013 subjects with multivessel coronary artery disease, 218 (22%) were deemed ineligible for coronary artery bypass graft surgery. The most common explicitly cited reasons for surgical ineligibility in the medical record were poor surgical targets (24%), advanced age (16%), and renal insufficiency (16%). After adjustment for known risk factors, documentation of surgical ineligibility remained independently associated with an increased risk of in-hospital (odds ratio, 6.26; 95% confidence interval, 2.16-18.15; P<0.001) and long-term mortality (hazard ratio, 2.98; 95% confidence interval, 1.88-4.72, P<0.001) after percutaneous coronary intervention. CONCLUSIONS: Documented surgical ineligibility is common and associated with significantly increased long-term mortality among patients undergoing percutaneous coronary intervention with unprotected left main or multivessel coronary disease, even after adjustment for known risk factors for adverse events during percutaneous revascularization.

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 Women's 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.

Causes of short-term readmission after percutaneous coronary intervention.

BACKGROUND: Rehospitalization within 30 days after an admission for percutaneous coronary intervention (PCI) is common, costly, and a future target for Medicare penalties. Causes of readmission after PCI are largely unknown. METHODS AND RESULTS: To illuminate the causes of PCI readmissions, patients with PCI readmitted within 30 days of discharge between 2007 and 2011 at 2 hospitals were identified, and their medical records were reviewed. Of 9288 PCIs, 9081 (97.8%) were alive at the end of the index hospitalization. Of these, 893 patients (9.8%) were readmitted within 30 days of discharge and included in the analysis. Among readmitted patients, 341 patients (38.1%) were readmitted for evaluation of recurrent chest pain or other symptoms concerning for angina, whereas 59 patients (6.6%) were readmitted for staged PCI without new symptoms. Complications of PCI accounted for 60 readmissions (6.7%). For cases in which chest pain or other symptoms concerning for angina prompted the readmission, 21 patients (6.2%) met criteria for myocardial infarction, and repeat PCI was performed in 54 patients (15.8%). The majority of chest pain patients (288; 84.4%) underwent ≥1 diagnostic imaging test, most commonly coronary angiography, and only 9 (2.6%) underwent target lesion revascularization. CONCLUSIONS: After PCI, readmissions within 30 days were seldom related to PCI complications but often for recurrent chest pain. Readmissions with recurrent chest pain infrequently met criteria for myocardial infarction but were associated with high rates of diagnostic testing.

Activation of human invariant natural killer T cells with a thioglycoside analogue of α-galactosylceramide.

Activation of CD1d-restricted invariant NKT (iNKT) cells with the glycolipid α-galactosylceramide (α-GalCer) confers protection against disease in murine models, however, clinical trials in humans have had limited impact. We synthesized a novel thioglycoside analogue of α-GalCer, denoted α-S-GalCer, and tested its efficacy for stimulating human iNKT cells in vitro. α-S-GalCer stimulated cytokine release by iNKT cells in a CD1d-dependent manner and primed CD1d(+) target cells for lysis. α-S-GalCer-stimulated iNKT cells induced maturation of monocyte-derived dendritic cells into antigen-presenting cells that released IL-12 and small amounts of IL-10. The nature and potency of α-S-GalCer and α-GalCer in human iNKT cell activation were similar. However, in contrast to α-GalCer, α-S-GalCer did not activate murine iNKT cells in vivo. Because of its enhanced stability in biological systems, α-S-GalCer may be superior to α-GalCer as a parent compound for developing adjuvant therapies for humans.