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Girotra S.,University of Iowa | Nallamothu B.K.,University of Michigan | Spertus J.A.,Saint Lukes Mid America Heart Institute | Spertus J.A.,University of Missouri - Kansas City | And 6 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND: Despite advances in resuscitation care in recent years, it is not clear whether survival and neurologic function after in-hospital cardiac arrest have improved over time. METHODS: We identified all adults who had an in-hospital cardiac arrest at 374 hospitals in the Get with the Guidelines-Resuscitation registry between 2000 and 2009. Using multi-variable regression, we examined temporal trends in risk-adjusted rates of survival to discharge. Additional analyses explored whether trends were due to improved survival during acute resuscitation or postresuscitation care and whether they occurred at the expense of greater neurologic disability in survivors. RESULTS: Among 84,625 hospitalized patients with cardiac arrest, 79.3% had an initial rhythm of asystole or pulseless electrical activity, and 20.7% had ventricular fibrillation or pulseless ventricular tachycardia. The proportion of cardiac arrests due to asystole or pulseless electrical activity increased over time (P<0.001 for trend). Risk-adjusted rates of survival to discharge increased from 13.7% in 2000 to 22.3% in 2009 (adjusted rate ratio per year, 1.04; 95% confidence interval [CI], 1.03 to 1.06; P<0.001 for trend). Survival improvement was similar in the two rhythm groups and was due to improvement in both acute resuscitation survival and postresuscitation survival. Rates of clinically significant neurologic disability among survivors decreased over time, with a risk-adjusted rate of 32.9% in 2000 and 28.1% in 2009 (adjusted rate ratio per year, 0.98; 95% CI, 0.97 to 1.00; P = 0.02 for trend). CONCLUSIONS: Both survival and neurologic outcomes after in-hospital cardiac arrest have improved during the past decade at hospitals participating in a large national quality-improvement registry. (Funded by the American Heart Association.) Copyright © 2012 Massachusetts Medical Society.

Jane-Wit D.,Section of Cardiovascular Medicine | Moeckel G.,Yale University | Pober J.S.,Yale University
Circulation | Year: 2013

BACKGROUND-: Cardiac allograft vasculopathy is the major cause of late allograft loss after heart transplantation. Cardiac allograft vasculopathy lesions contain alloreactive T cells that secrete interferon-γ, a vasculopathic cytokine, and occur more frequently in patients with donor-specific antibody. Pathological interactions between these immune effectors, representing cellular and humoral immunity, respectively, remain largely unexplored. METHODS AND RESULTS-: We used human panel reactive antibody to form membrane attack complexes on allogeneic endothelial cells in vitro and in vivo. Rather than inducing cytolysis, membrane attack complexes upregulated inflammatory genes, enhancing the capacity of endothelial cells to recruit and activate allogeneic interferon-γ-producing CD4 T cells in a manner dependent on the activation of noncanonical nuclear factor-κB signaling. Noncanonical nuclear factor-κB signaling was detected in situ within endothelial cells both in renal biopsies from transplantation patients with chronic antibody-mediated rejection and in panel-reactive antibody-treated human coronary artery xenografts in immunodeficient mice. On retransplantation into immunodeficient hosts engrafted with human T cells, panel-reactive antibody-treated grafts recruited more interferon-γ-producing T cells and enhanced cardiac allograft vasculopathy lesion formation. CONCLUSIONS-: Alloantibody and complement deposition on graft endothelial cells activates noncanonical nuclear factor-κB signaling, initiating a proinflammatory gene program that enhances alloreactive T cell activation and development of cardiac allograft vasculopathy. Noncanonical nuclear factor-κB signaling in endothelial cells, observed in human allograft specimens and implicated in lesion pathogenesis, may represent a target for new pharmacotherapies to halt the progression of cardiac allograft vasculopathy. © 2013 American Heart Association, Inc.

Gandhi P.U.,Section of Cardiovascular Medicine | Gandhi P.U.,Yale University | Testani J.M.,Yale University | Ahmad T.,Yale University
Current Heart Failure Reports | Year: 2015

Heart failure is a growing epidemic, and our understanding of the intricacies of its pathophysiology continues to evolve. Over the last decade, biomarkers of heart failure have been extensively investigated, particularly for diagnosis and risk stratification. While the natriuretic peptides remain the gold standard heart failure biomarker, they are plagued by their non-specific nature; furthermore, the strategy of natriuretic peptide-guided care remains elusive. Multiple candidate markers indicative of other physiologic aspects of heart failure have been identified and studied, including soluble ST2, galectin-3, and high-sensitivity cardiac troponins. Each of these biomarkers has the potential to provide unique therapeutically relevant information. Ultimately, a multi-marker approach may be applied to improve care of patients with heart failure. Definitive clinical trials and the use of advanced statistical analytic techniques are needed to truly determine the optimal strategy of biomarker-assisted diagnosis, prognostication, and management of patients who suffer from this devastating condition. © 2015, Springer Science+Business Media New York.

Krumholz H.M.,Section of Cardiovascular Medicine | Krumholz H.M.,Yale University | Krumholz H.M.,Center for Outcomes Research and Evaluation | Lin Z.,Center for Outcomes Research and Evaluation | And 8 more authors.
Circulation: Cardiovascular Quality and Outcomes | Year: 2011

Background-National attention has increasingly focused on readmission as a target for quality improvement. We present the development and validation of a model approved by the National Quality Forum and used by the Centers for Medicare & Medicaid Services for hospital-level public reporting of risk-standardized readmission rates for patients discharged from the hospital after an acute myocardial infarction. Methods and Results-We developed a hierarchical logistic regression model to calculate hospital risk-standardized 30-day all-cause readmission rates for patients hospitalized with acute myocardial infarction. The model was derived using Medicare claims data for a 2006 cohort and validated using claims and medical record data. The unadjusted readmission rate was 18.9%. The final model included 31 variables and had discrimination ranging from 8% observed 30-day readmission rate in the lowest predictive decile to 32% in the highest decile and a C statistic of 0.63. The 25th and 75th percentiles of the risk-standardized readmission rates across 3890 hospitals were 18.6% and 19.1%, with fifth and 95th percentiles of 18.0% and 19.9%, respectively. The odds of all-cause readmission for a hospital 1 SD above average were 1.35 times that of a hospital 1 SD below average. Hospital-level adjusted readmission rates developed using the claims model were similar to rates produced for the same cohort using a medical record model (correlation, 0.98; median difference, 0.02 percentage points). Conclusions-This claims-based model of hospital risk-standardized readmission rates for patients with acute myocardial infarction produces estimates that are excellent surrogates for those produced from a medical record model. (Circ Cardiovasc Qual Outcomes. 2011;4:243-252.) © 2011 American Heart Association, Inc.

Krumholz H.M.,Section of Cardiovascular Medicine | Krumholz H.M.,Yale University | Krumholz H.M.,Center for Outcomes Research and Evaluation | Krumholz H.M.,The New School | And 16 more authors.
Circulation | Year: 2011

Background-: Registry studies have suggested improvements in door-to-balloon times, but a national assessment of the trends in door-to-balloon times is lacking. Moreover, we do not know whether improvements in door-to-balloon times were shared equally among patient and hospital groups. Methods and results-: This analysis includes all patients reported by hospitals to the Centers for Medicare & Medicaid Services for inclusion in the time to percutaneous coronary intervention (acute myocardial infarction-8) inpatient measure from January 1, 2005, through September 30, 2010. For each calendar year, we summarized the characteristics of patients reported for the measure, including the number and percentage in each group, the median time to primary percutaneous coronary intervention, and the percentage with time to primary percutaneous coronary intervention within 75 minutes and within 90 minutes. Door-to-balloon time declined from a median of 96 minutes in the year ending December 31, 2005, to a median of 64 minutes in the 3 quarters ending September 30, 2010. There were corresponding increases in the percentage of patients who had times <90 minutes (44.2% to 91.4%) and <75 minutes (27.3% to 70.4%). The declines in median times were greatest among groups that had the highest median times during the first period: patients >75 years of age (median decline, 38 minutes), women (35 minutes), and blacks (42 minutes). CONCLUSION-: National progress has been achieved in the timeliness of treatment of patients with ST-segment-elevation myocardial infarction who undergo primary percutaneous coronary intervention. © 2011 American Heart Association, Inc.

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