Cees B. de Vos

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.

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.

Progression of atrial fibrillation in the REgistry on Cardiac rhythm disORDers assessing the control of Atrial Fibrillation cohort: Clinical correlates and the effect of rhythm-control therapy

INTRODUCTION Paroxysmal atrial fibrillation (AF) may progress to persistent AF. We studied the clinical correlates and the effect of rhythm-control strategy on AF progression. METHODS RecordAF was a worldwide prospective survey of AF management. Consecutive eligible patients with recent-onset AF were included and allocated to rate or rhythm control according to patient/physician choice. A total of 2,137 patients were followed up for 12 months. Atrial fibrillation progression was defined as a change from paroxysmal to persistent/permanent AF. RESULTS Progression of AF occurred in 318 patients (15%) after 1 year. Patients with AF progression were older; had a higher diastolic blood pressure; and more often had a history of coronary artery disease, stroke or transient ischemic attack, hypertension, or heart failure. Patients treated with rhythm control were less likely to show progression than those treated only with rate control (164/1542 [11%] vs 154/595 [26%], P < .001). Multivariable analysis showed that history of heart failure (odds ratio [OR] 2.2, 95% CI 1.7-2.9, P < .0001), history of hypertension (OR 1.5, 95% CI 1.1-2.0, P = .01), and rate control rather than rhythm control (OR 3.2, 95% CI 2.5-4.1, P < .0001) were independent predictors of AF progression. The propensity score-adjusted OR of AF progression in patients with rate rather than rhythm control was 3.3 (95% CI 2.4-4.6, P < .0001). CONCLUSIONS Although heart failure and hypertension are associated with AF progression, rhythm control is associated with lower risk of AF progression.

The likelihood of decreasing strokes in atrial fibrillation patients by strict application of guidelines

AIMS Despite the known increased stroke risk associated with AF and the benefit of oral anticoagulation (OAC) in high-risk patients, still approximately 20% of all ischaemic strokes are atrial fibrillation (AF) related. We aimed to evaluate the frequency of inappropriate anticoagulation in all patients admitted with AF associated ischaemic stroke and calculate the theoretical number of preventable strokes in case of proper guideline adherence and assess secondary stroke prevention at discharge. METHODS AND RESULTS In this cross-sectional study, all patients with ischaemic strokes admitted to our hospital during May 2003-August 2006 in whom the diagnosis AF was either known or established during hospital stay were identified. We studied if their admission and discharge antithrombotic therapy was in accordance with the published guidelines. Subsequently, we calculated the number of preventable strokes in case AF patients would have received adequate antithrombotic treatment on admission. On admission, in 51% of the OAC eligible known AF patients the drug was withheld. Improved antithrombotic guideline adherence potentially would have prevented 20 out of the 89 (22%) ischaemic strokes. At discharge at least 10% of the patients were still insufficiently protected against recurrent stroke. CONCLUSION Many known AF patients admitted with ischaemic stroke lack adequate antithrombotic treatment on admission. Antithrombotic guideline adherence in these patients has the potential to prevent a substantial number strokes. Secondary stroke prevention at discharge is also suboptimal.

Clinical and echocardiographic correlates of intra-atrial conduction delay

AIMS The total atrial conduction time (TACT) is an important electrophysiological parameter. We developed a new transthoracic echocardiographic tool (PA-TDI). The PA-TDI interval is a reflection of the TACT. In the present study, we evaluated the clinical and echocardiographic correlates of intra-atrial conduction delay. METHODS AND RESULTS We studied 427 patients without class I anti-arrhythmic agents or amiodarone. All patients underwent an echocardiogram and the PA-TDI interval was measured. Patient characteristics were recorded. The mean PA-TDI was 157 ± 22 ms. Multivariate linear regression analysis revealed that atrial fibrillation (AF) in history (B = 9.7; 95%CI 5.7-13.8; P < 0.001), hypertension (B = 5.5; 95%CI 1.4-9.8; P = 0.01), clinically relevant valve disease (B = 5.7; 95%CI 0.5-10.8; P = 0.03), age (B = 5; 95%CI 3.3-6.6; P < 0.001), and body mass index (BMI; B = 2.6; 95%CI 0.3-4.9; P = 0.026) were independently associated with the PA-TDI interval. On the echocardiogram: the aortic diameter (B = 0.7; 95%CI 0.2-1.2; P = 0.009), left atrial dimension (B = 0.9; 95%CI 0.5-1.3; P < 0.001), mitral valve E-wave deceleration time (B = 0.1; 95%CI 0.1-0.1; P < 0.001), aortic incompetence (B = 13; 95%CI 3.3-22.6; P = 0.008), and mitral incompetence (B = 11; 95%CI 3.6-17.5; P < 0.003) were independently associated with the PA-TDI interval. CONCLUSION This study is the largest to investigate the relation between the atrial conduction time, underlying heart diseases, and echocardiographic parameters. We found that the PA-TDI was independently prolonged in patients with a history of AF, hypertension, valve disease, higher age, and a higher BMI. Signs of diastolic dysfunction, valve incompetence, and enlarged atrium or aortic root on the echocardiogram were associated with a prolonged PA-TDI. This suggests that early and aggressive treatment of hypertension, diastolic dysfunction, and obesity could prevent intra-atrial conduction delay.

Use and Underuse of Oral Anticoagulation for Stroke Prevention in Atrial Fibrillation: Old and New Paradigms

Atrial fibrillation (AF) is the most common sustained arrhythmia of the Western world. The increased ischemic stroke risk of the AF patient is one of the most important clinical issues to manage. Despite the well-known benefit of oral anticoagulation in high-risk AF patients, these drugs are widely underused in daily practice all over the world. We describe old and new paradigms of the use of oral anticoagulation. In the future, increased comprehensibility of stroke risk scores, development of a validated clinical bleed risk score, and new patient and physician user-friendly antithrombotic medication may contribute to improved adequate use of oral anticoagulation in AF patients.

Characteristics, management and prognosis of elderly patients in the Euro Heart Survey on atrial fibrillation

Background and aims: Atrial fibrillation (AF) is the most frequent sustained arrhythmia of elderly patients, in whom it determines an increase in morbidity and mortality. Aim of this study was to assess age-related differences in the characteristics, management and prognosis of patients with AF in European cardiology practices. Methods: The Euro Heart Survey on AF was an observational study sponsored by the European Society of Cardiology. Patients were enrolled between 2003 and 2004 in 182 hospitals of 35 countries. For the purposes of this study, they were categorized into three age-groups: <65 (n=2124), 65–80 (n=2534) and >80 years (n=671). Follow-up was closed in 2005. Results: Compared with general population estimates, patients >80 years were underrepresented in the Euro Heart Survey. The oldest patients were less likely to be enrolled by university or specialized centers, to receive extensive diagnostic testing, and to receive oral anticoagulation despite a worse stroke risk profile. Furthermore, the oldest patients less often received rhythm control therapy, even when presenting with palpitations and non-permanent AF. During 1 year follow-up, elderly patients more often suffered a myocardial infarction, new onset heart failure and major bleedings. They had higher all-cause and cardiovascular mortality. Conclusions: Elderly patients with AF are less often referred to the cardiologist and, based on current guidelines, are inadequately studied and treated, compared to younger counterparts. Education on evidence-based management and the design of randomized controlled trials specifically targeting the elderly, should improve the management and prognosis of this frail segment of the AF population.

Systematic analysis of ECG predictors of sinus rhythm maintenance after electrical cardioversion for persistent atrial fibrillation

BACKGROUND Electrical cardioversion (ECV) is one of the rhythm control strategies in patients with persistent atrial fibrillation (AF). Unfortunately, recurrences of AF are common after ECV, which significantly limits the practical benefit of this treatment in patients with AF. OBJECTIVES The objectives of this study were to identify noninvasive complexity or frequency parameters obtained from the surface electrocardiogram (ECG) to predict sinus rhythm (SR) maintenance after ECV and to compare these ECG parameters with clinical predictors. METHODS We studied a wide variety of ECG-derived time- and frequency-domain AF complexity parameters in a prospective cohort of 502 patients with persistent AF referred for ECV. RESULTS During 1-year follow-up, 161 patients (32%) maintained SR. The best clinical predictor of SR maintenance was antiarrhythmic drug (AAD) treatment. A model including clinical parameters predicted SR maintenance with a mean cross-validated area under the receiver operating characteristic curve (AUC) of 0.62 ± 0.05. The best single ECG parameter was the dominant frequency (DF) on lead V6. Combining several ECG parameters predicted SR maintenance with a mean AUC of 0.64 ± 0.06. Combining clinical and ECG parameters improved prediction to a mean AUC of 0.67 ± 0.05. Although the DF was affected by AAD treatment, excluding patients taking AADs did not significantly lower the predictive performance captured by the ECG. CONCLUSION ECG-derived parameters predict SR maintenance during 1-year follow-up after ECV at least as good as known clinical predictors of rhythm outcome. The DF proved to be the most powerful ECG-derived predictor.