Predictors of in-hospital mortality in coronary artery dissection: Findings from the National Inpatient Sample 2009–2010

Background: The pathophysiology of coronary artery dissection (CD) remains poorly under­stood and little is known about the factors predicting mortality in these patients. We aimed to study the epidemiology of CD and predictors of mortality in these patients. Methods: All patients diagnosed with CD in the Nationwide Inpatient Sample 2009–2010 database using International Classification of Diseases ninth revision 414.12 were included in the study. Chronic conditions included in the analysis were diabetes mellitus, hypertension, hyperlipidemia, coronary artery disease (CAD), obesity, alcohol use, smoking, heart failure and ventricular arrhythmias. Non-cardiovascular conditions were connective tissue disorders, fibromuscular dysplasia, Ehlers-Danlos syndrome, Marfan’s syndrome, sarcoidosis, Crohn’s disease, polycystic kidney disease, rheumatoid arthritis, vasculitis including giant cell arteritis, polyarteritis nodosa and Takayasu’s disease, cocaine use, early or premature labor. Results: The prevalence of CD in the United States was 0.02% (n = 11,255), based on the hospital admissions reviewed in the database. The mean age was 63.25 years with women (64.62 years) being older than men (62.25 years) (p < 0.001). In-hospital mortality rate was 4.2%, with women (5.5%) having higher mortality than men (3.2%) (p = 0.009). Ventricular arrhythmias (OR 5.86, p < 0.001) predicted higher mortality, while hyperlipidemia (OR 0.26, p < 0.001) and CAD (OR 0.31, p = 0.001) predicted lower mortality in multivariate analysis. Conclusions: Our study demonstrated that CD was more prevalent in men but women had higher mortality than men. Age, heart failure and ventricular arrhythmias were independent predictors of increased mortality but hyperlipidemia CAD predicted lower mortality in patients with CD

Association of exclusive smokeless tobacco consumption with hypertension in an adult male rural population of India

<p>Abstract</p> <p>Introduction</p> <p>Tobacco consumption is a major source of mortality and morbidity in India . Prevalence of smokeless tobacco (ST) consumption in India is around 20%. Studies have shown increased prevalence of cardiovascular disease risk factors and an increased incidence of adverse cardiovascular events among the ST consumers. This is a cross-sectional study done to look into the association of exclusive smokeless tobacco consumption with hypertension, in an adult male rural population of north India.</p> <p>Methods</p> <p>All male residents of a village in north India above 15 years of age, who did not have any acute or chronic morbidity were included after taking an informed consent. Subjects were interviewed regarding their demographic profile, socioeconomic status and tobacco consuming habits. Current smokeless tobacco user was defined as one who has ever consumed tobacco orally in past 1 month. Blood pressure of the subjects was also recorded. Cut offs used for systolic and diastolic hypertension were 140 mm hg and 90 mm Hg respectively.</p> <p>Results</p> <p>443 subjects were included in the study. Prevalence of exclusive ST users was 21% while 19.4% consumed both forms and 26.6% did not take any form of tobacco. Mean systolic and diastolic BP were significantly higher in exclusive ST users(systolic BP=139.2+17.4,diastolic BP = 86.8+11.5)as compared to the non users(systolic BP= 135.7+18.8 , diastolic BP= 82.6 +11.5; p value < 0.05). The prevalence of diastolic hypertension was significantly higher in exclusive ST users as compared to non users ( 40.9%, 22.9% ;p value = 0.01) . The OR for diastolic hypertension in male ST users was 2.3( 95% C.I. = 1.3-4.3). Prevalence of systolic hypertension was higher in exclusive ST users too though this was not statistically significant (43%,36.4%;p value = 0.39.).</p> <p>Conclusion</p> <p>ST consumption is associated with increased prevalence of high BP in the adult male rural population.This is an indicator of increased predisposition to major adverse cardiac events later in their life time. Prevention of ST consumption could be an important intervention in preventing the ongoing upswing in prevalence of chronic heart disease.</p

Accelerated and interpretable oblique random survival forests

The oblique random survival forest (RSF) is an ensemble supervised learning method for right-censored outcomes. Trees in the oblique RSF are grown using linear combinations of predictors to create branches, whereas in the standard RSF, a single predictor is used. Oblique RSF ensembles often have higher prediction accuracy than standard RSF ensembles. However, assessing all possible linear combinations of predictors induces significant computational overhead that limits applications to large-scale data sets. In addition, few methods have been developed for interpretation of oblique RSF ensembles, and they remain more difficult to interpret compared to their axis-based counterparts. We introduce a method to increase computational efficiency of the oblique RSF and a method to estimate importance of individual predictor variables with the oblique RSF. Our strategy to reduce computational overhead makes use of Newton-Raphson scoring, a classical optimization technique that we apply to the Cox partial likelihood function within each non-leaf node of decision trees. We estimate the importance of individual predictors for the oblique RSF by negating each coefficient used for the given predictor in linear combinations, and then computing the reduction in out-of-bag accuracy. In general benchmarking experiments, we find that our implementation of the oblique RSF is approximately 450 times faster with equivalent discrimination and superior Brier score compared to existing software for oblique RSFs. We find in simulation studies that 'negation importance' discriminates between relevant and irrelevant predictors more reliably than permutation importance, Shapley additive explanations, and a previously introduced technique to measure variable importance with oblique RSFs based on analysis of variance. Methods introduced in the current study are available in the aorsf R package.Comment: 40 pages, 6 figure

Variation in Hospital-use and Outcomes Associated with Pulmonary Artery Catheterization in Heart Failure in the United States

Background There has been an increase in the use of pulmonary artery (PA) catheters in heart failure (HF) in the United States in recent years. However, patterns of hospital-use and trends in patient outcomes are not known. Methods and Results In the National Inpatient Sample 2001–2012, using ICD-9 codes we identified 11,888,525 adult (≥18 years) HF hospitalizations nationally, of which an estimated 75,209 (SE 0.6%) received a PA catheter. In 2001, the number of hospitals with ≥1 PA catheterization was 1753, decreasing to 1183 in 2011. The mean PA catheter use per hospital trended from 4.9/year in 2001 (limits 1–133) to 3.8/year in 2007 (limits 1–46), but increased to 5.5/year in 2011 (limits 1–70). During 2001–2006, PA catheterization declined across hospitals; however, in 2007–2012 there has been a disproportionate increase at hospitals with large bedsize, teaching programs, and advanced HF capabilities. The overall in-hospital mortality with PA catheter use was higher than without PA catheter use (13.1% vs. 3.4%, P<0.0001), however, in propensity-matched analysis, differences in mortality between these groups have attenuated over time – risk-adjusted odds ratio for mortality for PA-catheterization, 1.66 (95% CI 1.60–1.74) in 2001–2003 down to 1.04 (95% CI 0.97– 1.12) in 2010–2012. Conclusions There is substantial hospital-level variability in PA catheterization in HF along with increasing volume at fewer hospitals overrepresented by large, academic hospitals with advanced HF capabilities. This is accompanied by a decline in excess mortality associated with PA catheterization

Exercise Training in Patients with Heart Failure and Preserved Ejection Fraction: A Meta-analysis of Randomized Control Trials.

BACKGROUND: -Heart failure with preserved ejection fraction (HFPEF) is common and characterized by exercise intolerance and lack of proven effective therapies. Exercise training has been shown to be effective in improving cardiorespiratory fitness (CRF) in patients with systolic heart failure. In this meta-analysis, we aim to evaluate the effects of exercise training on CRF, quality of life and diastolic function in patients with HFPEF. METHODS AND RESULTS: -Randomized controlled clinical trials that evaluated the efficacy of exercise training in patients with HFPEF were included in this meta-analysis. Primary outcome of the study was change in CRF (measured as change in peak oxygen uptake). Impact of exercise training on quality of life (estimated using Minnesota living with heart failure score), left ventricular systolic and diastolic function was also assessed. The study included 276 patients that were enrolled in 6 randomized controlled trials. In the pooled data analysis, HFPEF patients undergoing exercise training had significantly improved CRF (L/min) (Mean difference: 2.72; 95% CI: 1.79 to 3.65) and quality of life (Mean difference: -3.97; 95% CI: -7.21 to -0.72) as compared with the control group. However, no significant change was observed in the systolic function [Ejection Fraction - Weighted Mean difference (WMD): 1.26; 95% CI: -0.13% to 2.66%] or diastolic function [E/A - WMD: 0.08; 95% CI:-0.01 to 0.16] with exercise training in HFPEF patients. CONCLUSIONS: -Exercise training in patients with HFPEF is associated with an improvement in CRF and quality of life without significant changes in left ventricular systolic or diastolic function

The interaction of cardiorespiratory fitness with obesity and the obesity paradox in cardiovascular disease

Overweight and obesity are well-established risk factors for most cardiovascular diseases (CVD), including coronary heart disease (CHD), heart failure (HF), and atrial fibrillation. Despite the strong link between excess adiposity and risk of CVD, growing evidence has demonstrated an obesity paradox in patients with CVD. This phenomenon is characterized by a better prognosis in overweight and mildly obese CVD patients than their leaner counterparts. Moreover, the worst outcomes are often incurred by underweight CVD patients, followed by those of normal weight or severely obese. The obesity paradox is now a well-established phenomenon across different types of CVD, and it occurs regardless of age and ethnicity of patients, and severity of CVD. Physical inactivity and low cardiorespiratory fitness (CRF) have long been recognized as major risk factors for CVD. In contrast, high levels of physical activity (PA) and CRF largely neutralize the adverse effects of excess adiposity and other traditional CVD risk factors, including hypertension, metabolic syndrome, and type-2 diabetes. Higher CRF also results in better CVD outcomes across different BMI groups and significantly alters the obesity paradox in patients with HF and CHD. Prognostic benefits of overweight/obesity tend to be limited to unfit patients with HF and CHD, and the obesity paradox usually disappears with improved levels of CRF. Nevertheless, increased PA and exercise training, to maintain or improve CRF, are effective, safe, and proven strategies for primary and secondary prevention of CVD in all weight groups. In this review, we discuss the current concepts of individual and combined contributions of fatness and fitness to CVD risk and prognosis. We then examine the influence of fitness on the obesity paradox in individuals with CVD

Insulin-Like Growth Factors Promote Vasculogenesis in Embryonic Stem Cells

The ability of embryonic stem cells to differentiate into endothelium and form functional blood vessels has been well established and can potentially be harnessed for therapeutic angiogenesis. However, after almost two decades of investigation in this field, limited knowledge exists for directing endothelial differentiation. A better understanding of the cellular mechanisms regulating vasculogenesis is required for the development of embryonic stem cell-based models and therapies. In this study, we elucidated the mechanistic role of insulin-like growth factors (IGF1 and 2) and IGF receptors (IGFR1 and 2) in endothelial differentiation using an embryonic stem cell embryoid body model. Both IGF1 or IGF2 predisposed embryonic stem to differentiate towards a mesodermal lineage, the endothelial precursor germ layer, as well as increased the generation of significantly more endothelial cells at later stages. Inhibition of IGFR1 signaling using neutralizing antibody or a pharmacological inhibitor, picropodophyllin, significantly reduced IGF-induced mesoderm and endothelial precursor cell formation. We confirmed that IGF-IGFR1 signaling stabilizes HIF1α and leads to up-regulation of VEGF during vasculogenesis in embryoid bodies. Understanding the mechanisms that are critical for vasculogenesis in various models will bring us one step closer to enabling cell based therapies for neovascularization