Ron Pisters

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). CONCLUSIONS 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.

Original ResearchThromboembolismRefining 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). CONCLUSIONS 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.

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.

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.

Quarterly Focus Issue: Heart Rhythm DisorderClinical Research: Atrial FibrillationProgression 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.

Nurse-led care vs. usual care for patients with atrial fibrillation: results of a randomized trial of integrated chronic care vs. routine clinical care in ambulatory patients with atrial fibrillation

AIMS The management of patients with atrial fibrillation (AF) is often inadequate due to deficient adherence to the guidelines. A nurse-led AF clinic providing integrated chronic care to improve guideline adherence and activate patients in their role, may effectively reduce morbidity and mortality but such care has not been tested in a large randomized trial. Therefore, we performed a randomized clinical trial to compare the AF clinic with routine clinical care in patients with AF. METHODS AND RESULTS We randomly assigned 712 patients with AF to nurse-led care and usual care. Nurse-led care consisted of guidelines based, software supported integrated chronic care supervised by a cardiologist. The primary endpoint was a composite of cardiovascular hospitalization and cardiovascular death. Duration of follow-up was at least 12 months. Adherence to guideline recommendations was significantly better in the nurse-led care group. After a mean of 22 months, the primary endpoint occurred in 14.3% of 356 patients of the nurse-led care group compared with 20.8% of 356 patients receiving usual care [hazard ratio: 0.65; 95% confidence interval (CI) 0.45-0.93; P= 0.017]. Cardiovascular death occurred in 1.1% in the nurse-led care vs. 3.9% in the usual care group (hazard ratio: 0.28; 95% CI: 0.09-0.85; P= 0.025). Cardiovascular hospitalization amounted (13.5 vs. 19.1%, respectively, hazard ratio: 0.66; 95% CI: 0.46-0.96, P= 0.029). CONCLUSION Nurse-led care of patients with AF is superior to usual care provided by a cardiologist in terms of cardiovascular hospitalizations and cardiovascular mortality. Trial registration information: Clinicaltrials.gov identifier number: NCT00391872.

Atrial Tissue Doppler Imaging For Prediction Of New-Onset Atrial Fibrillation

Background: The total atrial conduction time (TACT) is an independent predictor of atrial fibrillation (AF). A new transthoracic echocardiographic tool to determine TACT by tissue Doppler imaging (PA-TDI (the time from the initiation of the P wave on the ECG (lead II) to the A′ wave on the lateral left atrial tissue Doppler tracing)) has been developed recently. Objective: To test the hypothesis that measurement of PA-TDI enables prediction of new-onset AF. Methods: 249 Patients without a history of AF were studied. All patients underwent an echocardiogram and the PA-TDI interval was measured. Patient characteristics and rhythm at follow-up were recorded. Results: During a mean (SD) follow-up of 680 (290) days, 15 patients (6%) developed new-onset AF. These patients had a longer PA-TDI interval than patients who remained in sinus rhythm (172 (25) ms vs 150 (20) ms, p = 0.001). Furthermore, the patients developing AF were older, more often had a history of heart failure or chronic obstructive pulmonary disease, more often used α blockers, had enlarged left atria and more frequently mitral incompetence on the echocardiogram. After adjusting for potential confounders, Cox regression showed that PA-TDI was independently associated with new-onset AF (OR = 1.375; 95% CI 1.037 to 1.823; p = 0.027). The 2-year incidence of AF was 33% in patients with a PA-TDI interval >190 ms versus 0% in patients with a PA-TDI interval <130 ms (p = 0.002). Conclusions: A prolonged PA-TDI interval may predict the development of new-onset AF. This measure may be used to identify patients at risk in future strategies to prevent the development or complications of AF.

Personalized management of atrial fibrillation: Proceedings from the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association consensus conference.

The management of atrial fibrillation (AF) has seen marked changes in past years, with the introduction of new oral anticoagulants, new antiarrhythmic drugs, and the emergence of catheter ablation as a common intervention for rhythm control. Furthermore, new technologies enhance our ability to detect AF. Most clinical management decisions in AF patients can be based on validated parameters that encompass type of presentation, clinical factors, electrocardiogram analysis, and cardiac imaging. Despite these advances, patients with AF are still at increased risk for death, stroke, heart failure, and hospitalizations. During the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association (AFNET/EHRA) consensus conference, we identified the following opportunities to personalize management of AF in a better manner with a view to improve outcomes by integrating atrial morphology and damage, brain imaging, information on genetic predisposition, systemic or local inflammation, and markers for cardiac strain. Each of these promising avenues requires validation in the context of existing risk factors in patients. More importantly, a new taxonomy of AF may be needed based on the pathophysiological type of AF to allow personalized management of AF to come to full fruition. Continued translational research efforts are needed to personalize management of this prevalent disease in a better manner. All the efforts are expected to improve the management of patients with AF based on personalized therapy.

Clinical correlates of immediate success and outcome at 1-year follow-up of real-world cardioversion of atrial fibrillation: the Euro Heart Survey

AIMS In atrial fibrillation (AF) cardioversion is the cornerstone of the rhythm management strategy despite the lack of contemporary data on acute and long-term success. We aim to describe present-day cardioversion of AF and identify characteristics associated with immediate and long-term outcome. METHODS AND RESULTS Based on the 5333 AF patients enrolled in the multi-centre prospective Euro Heart Survey on AF we selected the 1801 patients undergoing cardioversion at enrolment. Sinus rhythm (SR) was restored in 630 of 712 (88%), 458 of 643 (71%), and 333 of 446 (75%) (P< 0.001) of the electrical (ECV), intravenous (ivCCV), and oral (oCCV) chemical cardioversions, respectively, at the cost of few (4.2%) major complications. In multivariate analysis, absence of chronic obstructive pulmonary disease (COPD) (P< 0.001), presence of paroxysmal AF (PAF) (P= 0.013), and use of biphasic waveform (P= 0.018) were predictors of successful ECV. For ivCCV PAF (P< 0.001), absence of valvular heart disease (P= 0.004), and heart failure (P= 0.009), the presence of hypertension (P= 0.018) and coronary artery disease (P= 0.007) were predictive. Success of oCCV was driven by PAF (P< 0.001) and a smaller left atrial dimension (P= 0.001). At 1-year follow-up 893 of 1271 (70%) patients were in SR. Multivariate analysis revealed PAF (P< 0.001), shorter total AF history (P< 0.001), continuous use of Class Ic drugs or amiodarone during follow-up (P< 0.001), absence of COPD (P= 0.003), younger age (P= 0.004), and smaller left atrial dimension (P= 0.005) as independent predictors of SR at 1-year follow-up. CONCLUSIONS Contemporary cardioversion of AF is routinely successfully and safely performed with a high proportion of patients in SR at 1-year follow-up.

Autonomic trigger patterns and anti-arrhythmic treatment of paroxysmal atrial fibrillation: data from the Euro Heart Survey

AIMS To investigate the clinical characteristics, management, and outcome of patients with paroxysmal atrial fibrillation (AF) associated with autonomic triggers. METHODS AND RESULTS One thousand five hundred and seventeen patients with paroxysmal AF participated in the Euro Heart Survey on AF. We categorized patients according to trigger pattern as reported by the physician: adrenergic (AF associated with exercise, emotion or during daytime only and absence of vagal triggers), vagal (postprandial or night time only, without presence of adrenergic triggers) and mixed (combination of vagal and adrenergic triggers). Vagal AF was found in 91 patients (6%), adrenergic in 229 patients (15%) and mixed in 175 (12%) patients. Underlying heart disease was equally prevalent in the three groups. Among patients with vagal AF, 73% were treated with non-recommended drugs according to the guidelines. In vagal AF, non-recommended treatment was associated with a shift to persistent or permanent AF in 19% of the patients, compared with none in the group receiving recommended treatment (P = 0.06). CONCLUSION This study is the first to address the issue of autonomic trigger patterns and AF in a large population. Autonomic trigger patterns were seen frequently in paroxysmal AF patients. Autonomic influences should be taken into consideration since non-recommended treatment may result in aggravation of vagal AF.