Effect of Systemic Hypertension With Versus Without Left Ventricular Hypertrophy on the Progression of Atrial Fibrillation (from the Euro Heart Survey).

Hypertension is a risk factor for both progression of atrial fibrillation (AF) and development of AF-related complications, that is major adverse cardiac and cerebrovascular events (MACCE). It is unknown whether left ventricular hypertrophy (LVH) as a consequence of hypertension is also a risk factor for both these end points. We aimed to assess this in low-risk AF patients, also assessing gender-related differences. We included 799 patients from the Euro Heart Survey with nonvalvular AF and a baseline echocardiogram. Patients with and without hypertension were included. End points after 1 year were occurrence of AF progression, that is paroxysmal AF becoming persistent and/or permanent AF, and MACCE. Echocardiographic LVH was present in 33% of 379 hypertensive patients. AF progression after 1 year occurred in 10.2% of 373 patients with rhythm follow-up. In hypertensive patients with LVH, AF progression occurred more frequently as compared with hypertensive patients without LVH (23.3% vs 8.8%, p = 0.011). In hypertensive AF patients, LVH was the most important multivariably adjusted determinant of AF progression on multivariable logistic regression (odds ratio 4.84, 95% confidence interval 1.70 to 13.78, p = 0.003). This effect was only seen in male patients (27.5% vs 5.8%, p = 0.002), while in female hypertensive patients, no differences were found in AF progression rates regarding the presence or absence of LVH (15.2% vs 15.0%, p = 0.999). No differences were seen in MACCE for hypertensive patients with and without LVH. In conclusion, in men with hypertension, LVH is associated with AF progression. This association seems to be absent in hypertensive women

Progression From Paroxysmal to Persistent Atrial Fibrillation. Clinical Correlates and Prognosis

Objectives: We investigated clinical correlates of atrial fibrillation (AF) progression and evaluated the prognosis of patients demonstrating AF progression in a large population. Background: Progression of paroxysmal AF to more sustained forms is frequently seen. However, not all patients will progress to persistent AF. Methods: We included 1,219 patients with paroxysmal AF who participated in the Euro Heart Survey on AF and had a known rhythm status at follow-up. Patients who experienced AF progression after 1 year of follow-up were identified. Results: Progression of AF occurred in 178 (15%) patients. Multivariate analysis showed that heart failure, age, previous transient ischemic attack or stroke, chronic obstructive pulmonary disease, and hypertension were the only independent predictors of AF progression. Using the regression coefficient as a benchmark, we calculated the HATCH score. Nearly 50% of the patients with a HATCH score >5 progressed to persistent AF compared with only 6% of the patients with a HATCH score of 0. During follow-up, patients with AF progression were more often admitted to the hospital and had more major adverse cardiovascular events. Conclusions: A substantial number of patients progress to sustained AF within 1 year. The clinical outcome of these patients regarding hospital admissions and major adverse cardiovascular events was worse compared with patients demonstrating no AF progression. Factors known to cause atrial structural remodeling (age and underlying heart disease) were independent predictors of AF progression. The HATCH score may help to identify patients who are likely to progress to sustained forms of AF in the near future. \ua9 2010 American College of Cardiology Foundation

Prediction of overall survival for patients with metastatic castration-resistant prostate cancer : development of a prognostic model through a crowdsourced challenge with open clinical trial data

Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest-namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial-ENTHUSE M1-in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. Findings 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0.791; Bayes factor >5) and surpassed the reference model (iAUC 0.743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3.32, 95% CI 2.39-4.62, p Interpretation Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer.Peer reviewe

Gender-related differences in presentation, treatment, and outcome of patients with atrial fibrillation in Europe - A report from the Euro Heart Survey on atrial fibrillation

Objectives This study sought to investigate gender-related differences in patients with atrial fibrillation (AF) in Europe. Background Gender-related differences may play a significant role in AF. Methods We analyzed the data of 5,333 patients (42% female) enrolled in the Euro Heart Survey on Atrial Fibrillation. Results Compared with men, the women were older, had a lower quality of life (QoL), had more comorbidities, more often had heart failure (HF) with preserved left ventricular systolic function (18% vs. 7%, p < 0.001), and less often had HF with systolic dysfunction (17% vs. 26%, p < 0.001). Among patients with typical AF symptoms (56% of women, 49% of men), there was no gender-related difference in the choice of rate or rhythm control. Among patients with atypical or no symptoms (44% of women, 51% of men), women less frequently underwent rhythm control (39% vs. 51%, p < 0.001) than did men. Women underwent less electrical cardioversion (22% vs. 28%, p < 0.001). Prescription of oral anticoagulants was identical (65%) in both genders. One-year outcome was similar except that women had a higher chance for stroke (odds ratio 1.83 in multivariable regression analysis, p = 0.019). Conclusions Women with AF had more comorbidities, more HF with preserved systolic function, and a lower QoL than men. In the large group with atypical or no symptoms, women were treated appropriately more conservatively with less rhythm control than men. Women had a higher chance for stroke. Long-term QoL changes and other morbidities and mortality were similar

Gender-Related Differences in Presentation, Treatment, and Outcome of Patients With Atrial Fibrillation in Europe. A Report From the Euro Heart Survey on Atrial Fibrillation

Objectives: This study sought to investigate gender-related differences in patients with atrial fibrillation (AF) in Europe. Background: Gender-related differences may play a significant role in AF. Methods: We analyzed the data of 5,333 patients (42% female) enrolled in the Euro Heart Survey on Atrial Fibrillation. Results: Compared with men, the women were older, had a lower quality of life (QoL), had more comorbidities, more often had heart failure (HF) with preserved left ventricular systolic function (18% vs. 7%, p < 0.001), and less often had HF with systolic dysfunction (17% vs. 26%, p < 0.001). Among patients with typical AF symptoms (56% of women, 49% of men), there was no gender-related difference in the choice of rate or rhythm control. Among patients with atypical or no symptoms (44% of women, 51% of men), women less frequently underwent rhythm control (39% vs. 51%, p < 0.001) than did men. Women underwent less electrical cardioversion (22% vs. 28%, p < 0.001). Prescription of oral anticoagulants was identical (65%) in both genders. One-year outcome was similar except that women had a higher chance for stroke (odds ratio 1.83 in multivariable regression analysis, p = 0.019). Conclusions: Women with AF had more comorbidities, more HF with preserved systolic function, and a lower QoL than men. In the large group with atypical or no symptoms, women were treated appropriately more conservatively with less rhythm control than men. Women had a higher chance for stroke. Long-term QoL changes and other morbidities and mortality were similar. © 2007 American College of Cardiology Foundation

Atrial fibrillation management: a prospective survey in ESC Member Countries - The Euro Heart Survey on Atrial Fibrillation

Aims To describe atrial fibrillation (AF) management in member countries of the European Society of Cardiology (ESC) and to verify cardiology practices against guidelines. Methods and results Among 182 hospitals in 35 countries, 5333 ambulant and hospitalized AF patients were enrolled, in 2003 and 2004. AF was primary or secondary diagnosis, and was confirmed on ECG in the preceding 12 months. Clinical type of AF was reported to be first detected in 978, paroxysmal in 1517, persistent in 1167, and permanent in 1547 patients. Concomitant diseases were present in 90% of all patients, causing risk factors for stroke to be also highly prevalent (86%). As many as 69% of patients were symptomatic at the time of the survey; among asymptomatic patients, 54% were previously experienced symptoms. Oral anticoagulation was prescribed in 67 and 49% of eligible and ineligible patients, respectively. A rhythm control strategy was applied in 67% of currently symptomatic patients and in 44% of patients who never experienced symptoms. Conclusion This survey provides a unique snapshot of current AF management in ESC member countries. Discordance between guidelines and practice was found regarding several issues on stroke prevention and antiarrhythmic therapy

Diabetes known or newly detected, but not impaired glucose regulation, has a negative influence on 1-year outcome in patients with coronary artery disease: A report from the Euro Heart Survey on diabetes and the heart

Aims: Although diabetes is known to be a major contributor to cardiovascular diseases, as well as an independent predictor for adverse outcomes in patients with coronary artery disease (CAD), information on the prognosis of patients with CAD and newly diagnosed diabetes or impaired glucose regulation (IGR) is scarce. The objective of this study was to explore 1-year outcome in relation to different glucometabolic states of patients participating in the Euro Heart Survey on diabetes and the heart. Methods and results: In 4676 out of 4961 patients, information on the relation between 1-year outcome and glucometabolic state, which was based on oral glucose tolerance test (OGTT) or fasting glucose plasma, was available. A normal glucose metabolism was identified in 947 patients, IGR (impaired fasting glucose or impaired glucose tolerance) in 1116 patients, and diabetes in 1877 patients of whom 1425 were previously diagnosed and 452 newly diagnosed. In total, 736 patients could not be classified, as no OGTT or fasting plasma glucose was performed. Previously recognized and newly detected diabetes was associated with an increased risk of 1-year mortality when compared with patients with normal glucose regulation [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.5-3.8 and HR 2.0, 95% CI 1.1-3.6, respectively)]. IGR, however, could not be identified as an independent predictor for 1-year mortality (HR 1.1, 95% CI 0.6-1.9). Conclusion: This study confirmed that patients with CAD and known diabetes are at high risk for mortality and cardiovascular events and demonstrated that patients with newly diagnosed diabetes are at intermediate risk for adverse outcomes. IGR, however, could not be identified as an independent predictor for adverse outcomes during the 1-year follow-up period. © The European Society of Cardiology 2006. All rights reserved

Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: The Euro Heart Survey on atrial fibrillation

Background: Contemporary clinical risk stratification schemata for predicting stroke and thromboembolism (TE) in patients with atrial fibrillation (AF) are largely derived from risk factors identified from trial cohorts. Thus, many potential risk factors have not been included. Methods: We refined the 2006 Birmingham/National Institute for Health and Clinical Excellence (NICE) stroke risk stratification schema into a risk factor-based approach by reclassifying and/or incorporating additional new risk factors where relevant. This schema was then compared with existing stroke risk stratification schema in a real-world cohort of patients with AF (n = 1,084) from the Euro Heart Survey for AF. Results: Risk categorization differed widely between the different schemes compared. Patients classified as high risk ranged from 10.2% with the Framingham schema to 75.7% with the Birmingham 2009 schema. The classic CHADS 2 (Congestive heart failure, Hypertension, Age > 75, Diabetes, prior Stroke/transient ischemic attack) schema categorized the largest proportion (61.9%) into the intermediate-risk strata, whereas the Birmingham 2009 schema classified 15.1% into this category. The Birmingham 2009 schema classified only 9.2% as low risk, whereas the Framingham scheme categorized 48.3% as low risk. Calculated C-statistics suggested modest predictive value of all schema for TE. The Birmingham 2009 schema fared marginally better (C-statistic, 0.606) than CHADS 2 . However, those classified as low risk by the Birmingham 2009 and NICE schema were truly low risk with no TE events recorded, whereas TE events occurred in 1.4% of low-risk CHADS 2 subjects. When expressed as a scoring system, the Birmingham 2009 schema (CHA 2 DS 2 -VASc acronym) showed an increase in TE rate with increasing scores ( P value for trend = .003). Conclusion: Our novel, simple stroke risk stratification schema, based on a risk factor approach, provides some improvement in predictive value for TE over the CHADS 2 schema, with low event rates in low-risk subjects and the classification of only a small proportion of subjects into the intermediate-risk category. This schema could improve our approach to stroke risk stratification in patients with AF. © 2010 American College of Chest Physicians

A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: The euro heart survey

Objective: Despite extensive use of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) and the increased bleeding risk associated with such OAC use, no handy quantification tool for assessing this risk exists. We aimed to develop a practical risk score to estimate the 1-year risk for major bleeding (intracranial, hospitalization, hemoglobin decrease >2 g/L, and/or transfusion) in a cohort of real-world patients with AF. Methods: Based on 3,978 patients in the Euro Heart Survey on AF with complete follow-up, all univariate bleeding risk factors in this cohort were used in a multivariate analysis along with historical bleeding risk factors. A new bleeding risk score termed HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (> 65 years), Drugs/alcohol concomitantly) was calculated, incorporating risk factors from the derivation cohort. Results: Fifty-three (1.5%) major bleeds occurred during 1-year follow-up. The annual bleeding rate increased with increasing risk factors. The predictive accuracy in the overall population using significant risk factors in the derivation cohort (C statistic 0.72) was consistent when applied in several subgroups. Application of the new bleeding risk score (HAS-BLED) gave similar C statistics except where patients were receiving antiplatelet agents alone or no antithrombotic therapy, with C statistics of 0.91 and 0.85, respectively. Conclusion: This simple, novel bleeding risk score (HAS-BLED) provides a practical tool to assess the individual bleeding risk of real-world patients with AF, potentially supporting clinical decision making regarding antithrombotic therapy in patients with AF. © 2010 American College of Chest Physicians