Bart A. Mulder

Lenient vs. strict rate control in patients with atrial fibrillation and heart failure: a post-hoc analysis of the RACE II study

It is unknown whether lenient rate control is an acceptable strategy in patients with AF and heart failure. We evaluated differences in outcome in patients with AF and heart failure treated with lenient or strict rate control.

Effect of nebivolol on outcome in elderly patients with heart failure and atrial fibrillation: insights from SENIORS

Beneficial effects of beta‐blockade remain unclear in heart failure patients who have atrial fibrillation (AF), especially in the elderly. We evaluated the effect of nebivolol on cardiovascular outcomes in elderly patients with heart failure and AF.

Digoxin in patients with permanent atrial fibrillation: Data from the RACE II study

BACKGROUND The Atrial Fibrillation Follow-up Investigation of Rhythm Management trial showed that digoxin was associated with increased mortality in patients with atrial fibrillation. OBJECTIVES To assess the association of digoxin with cardiovascular (CV) morbidity and mortality in patients with permanent atrial fibrillation enrolled in the Dutch Rate Control Efficacy in Permanent AF: A Comparison Between Lenient Versus Strict Rate Control II trial as well as to assess the role of digoxin to achieve heart rate targets. METHODS The primary outcome was a composite of CV morbidity and mortality. Secondary outcomes included CV hospitalization and all-cause mortality or heart failure (HF) hospitalization. Of the 614 patients, 608 (99%) completed the dose-adjustment phase. Outcome events were analyzed from the end of the dose-adjustment phase until the end of follow-up. The median follow-up period was 2.9 years (interquartile range 2.7-3.0 years). RESULTS In total, 284 patients (46.7%) used digoxin after the dose-adjustment phase (median dosage 0.250 mg; interquartile range 0.0625-0.750 mg). These patients were more often women, previously admitted for HF, had an increased left ventricular end-systolic diameter, and more often randomized to strict rate control. By using Cox proportional hazards regression analysis, the use of digoxin was not associated with an increased risk for the primary and secondary outcomes. For the primary outcome, the 3-year estimated cumulative incidence was 12.9% vs 13.4% in the digoxin group vs the no-digoxin group (unadjusted hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.62-1.52). Incidence was 19.4% vs. 19.5% for CV hospitalization (unadjusted HR 1.00; 95% CI 0.69-1.45) and 6.6% vs. 9.9% for all-cause mortality or HF hospitalization (unadjusted HR 0.62; 95% CI 0.34-1.13) in the digoxin group vs the no-digoxin group. CONCLUSION The use of digoxin was not associated with increased morbidity and mortality.

Long-term results of surgical minimally invasive pulmonary vein isolation for paroxysmal lone atrial fibrillation

AIMS Transcatheter pulmonary vein ablation is the current treatment of choice for symptomatic drug-refractory atrial fibrillation (AF). Video-assisted surgical pulmonary vein isolation (sPVI) is an alternative therapy to percutaneous ablation for the treatment of AF. Long-term results of sPVI are currently unknown. The aim of this study was to report on the long-term efficacy and safety of sPVI in patients with paroxysmal AF. METHODS AND RESULTS The study design was observational and retrospective. From July 2005 to January 2011, 42 patients with drug-refractory paroxysmal AF underwent video-assisted sPVI in two different centres. Patients were eligible for sPVI when suffering from symptomatic, drug-refractory paroxysmal AF and they agreed to the alternative of sPVI. The median preoperative AF duration was 24 months (range 3-200). Success was defined as the absence of AF on 24 h or 96 h Holter monitoring during follow-up, off antiarrhythmic drugs (AAD). Adverse events and follow-up monitoring were based on the Heart Rhythm Society Consensus Statement 2012 for the catheter and surgical ablation of AF. Mean age was 55 ± 10 years, and 76% were males. After a mean follow-up of 5 years (SD 1.7), 69% of all patients were free from atrial arrhythmias without the use of AAD, and 83% with the use of AAD. Major peri-procedural adverse events occurred in four (9.5%) patients, no strokes or mortalities were registered during long-term follow-up. CONCLUSION This retrospective study shows that sPVI for the treatment of paroxysmal AF is effective and that the outcomes are maintained at long-term follow-up.

Atrial reverse remodelling is associated with outcome of cardiac resynchronization therapy

AIMS To study the prognostic effect of atrial reverse remodelling on outcome of cardiac resynchronization therapy (CRT). METHODS AND RESULTS Patients receiving a CRT device in the University Medical Centre Groningen were included. Atrial reverse remodelling was defined as a ≥10% reduction in left atrial volume index at 6-month follow-up. Success of CRT was defined as ventricular reverse remodelling with a reduction in left ventricular end-systolic volume of ≥15% at 6-month follow-up. Primary endpoint was all-cause mortality or heart failure hospitalizations. A total of 365 patients (mean age 65.1 ± 11.0 years, 73% men) were included; among them, 221 (61%) were in sinus rhythm and had no prior atrial fibrillation (AF), and 144 patients (39%) had a history of AF. During a mean follow up of 2.0 ± 1.0 years, 49 patients died. Cox regression analysis revealed that patients with no atrial and no ventricular reverse remodelling had the worst outcome (hazard ratio 3.1, 95% confidence interval 1.4-7.1, P = 0.006). Outcome in patients with only atrial reverse remodelling was comparable with outcome in patients with both atrial and ventricular reverse remodelling (hazard ratio 2.0, 95% confidence interval 0.7-5.6, P = 0.21). CONCLUSION Patients without atrial and ventricular reverse remodelling have the worst outcome. Patients with only atrial reverse remodelling have improved left ventricular diastolic filling during follow-up and demonstrate a comparable outcome with patients with both atrial and ventricular reverse remodelling. Assessment of atrial reverse remodelling may provide additional prognostic information in determining CRT outcome.

Pulmonary vein isolation of symptomatic refractory paroxysmal and persistent atrial fibrillation: A single centre and single operator experience in the Netherlands

Aim. To investigate long-term outcome and to determine predictors of successful pulmonary vein isolation (PVI) in patients with symptomatic paroxysmal or persistent atrial fibrillation (AF) who are refractory or intolerant to antiarrhythmic drugs.Background. The treatment of AF has traditionally been pharmacological aimed at rate or rhythm control. However, rhythm control remains difficult to establish. PVI is reported to be effective in selected patient groups.Methods. Ninety-nine consecutive patients with a mean age of 54±10 years who had paroxysmal or persistent AF were treated in the University Medical Center Groningen. All patients underwent PVI by the same electrophysiologist. Successful PVI was defined as absence of AF on Holter or electrocardiogram (ECG), and no symptoms of AF.Results. After six months of follow-up, 60 (61%) patients were free of AF episodes, both on 96-hour Holter monitoring and on ECGs, and had no symptoms related to AF. Thirty-nine of these 60 patients (65%) were no longer treated with any class I or III antiarrhythmic drugs. Independent determinants of successful PVI were paroxysmal AF (OR 18 [3.5–93], p=0.001), and left pulmonary vein ablation time >55 minutes (OR 15 [2.7–81], p=0.002). Left atrial (parasternal view 42±6 vs. 40±5 mm, p<0.05 and apical view 61±9 vs. 58±8 mm, p<0.05) and right atrial (59±7 vs. 56±5 mm, p<0.05) sizes decreased significantly in the successfully treated patients after six months of follow-up.Conclusion. Independent determinants of a successful outcome after PVI are paroxysmal AF and a longer left atrial ablation time. (Neth Heart J 2009;17:366–72.)

Stroke aetiology in heart failure: towards patient-tailored prevention of stroke.

Heart failure is one of the largest disease problems of our time, being named one of the epidemics in cardiovascular disease of the 21st century. At present the incidence in the USA approaches 10 per 1000 aged 65 years and older, of whom 75% have antecedent hypertension. Although survival has improved over the years, the prognosis still is not benign at all: 50% of patients with heart failure will die within 5 years. Stroke contributes to this increased mortality rate and also to an impaired functional capacity and an impaired quality of life. The mechanisms involved in the occurrence of stroke are heterogeneous, also in patients with heart failure. Stasis of the blood in the dilated hypokinetic or akinetic chambers of the heart and atrial fibrillation are widely recognized as underlying mechanisms. In addition, concomitant vascular abnormalities, endothelial dysfunction, and an increased prothrombotic activity in association with activation of the sympathetic nervous system and of the renin–angiotensin–aldosterone system inducing increased platelet aggregation and reduced fibrinolysis may contribute to this deleterious complication. 8 This means that in heart failure, the syndrome of heart failure contributes not only to the increased risk of stroke but also and probably differentially to the associated underlying diseases such as hypertension, coronary artery disease, and diabetes mellitus. The incidence of stroke in patients with heart failure ranges between 1.3 and 3.9 per 100 patients years and seems to decline during the last years. Unless atrial fibrillation is present, key evidence for the benefit of oral anticoagulation in heart failure is lacking. Current European and Northern American guidelines therefore recommend oral anticoagulation in patients with heart failure only in the presence of concomitant atrial fibrillation or other cardiovascular disorders associated with an increased risk of thrombosis, such as amyloidosis. Vemmos et al. have presented data about the aetiology of stroke in patients with heart failure. They included 2904 patients with acute stroke, of whom 283 (9.7%) had heart failure. Although stroke severity was comparable between patients with and without heart failure, there were major differences in the aetiology of stroke. Cardioembolism and hypoperfusion were more often observed in heart failure patients. In contrast, lacunar strokes and intracerebral haemorrhages occurred more frequently in patients without heart failure. In the group of heart failure patients with stroke, 144 (51%) had concomitant atrial fibrillation. In these patients with atrial fibrillation, cardioembolism was the major cause of stroke, whereas in those without documented atrial fibrillation the mechanism of stroke was more dependent on the underlying disease. In patients with hypertension or coronary artery disease, strokes were predominantly atherosclerotic or lacunar as compared with cardioembolism in heart failure patients with dilated cardiomyopathy or valvular diseases. They also assessed mortality during a mean follow-up of almost 4 years. As could be expected, mortality was higher in patients with heart failure and was associated with the severity of heart failure and the severity of stroke. The data from this study are of interest and highlight an important problem in patients with heart failure. Prognosis is still poor and stroke contributes to this impaired outcome. So far, vitamin K antagonists, aspirin, and/or clopidogrel have not been proven effective for prevention of stroke or for increasing survival. One of the reasons for the latter may be the various underlying stroke aetiologies present in the cardiovascular population, even more in patients with heart failure. Although the number of patients with heart failure was relatively small in the present study, the data provided are convincing and not unexpected. Stroke aetiology seems to depend mainly on the underlying cardiovascular disease and the concomitant presence of atrial fibrillation in association with pathophysiological processes induced by heart failure itself. The complex mechanisms underlying stroke are still not fully understood. Depending on the type of patient, different pathophysiological processes may play a role, which probably

Heart rate and outcome in heart failure with reduced ejection fraction: Differences between atrial fibrillation and sinus rhythm—A CIBIS II analysis

Heart rate has been associated with prognosis in patients with heart failure with reduced ejection fraction (HFREF) and sinus rhythm; whether this also holds true in patients with atrial fibrillation (AF) is unknown.

Predicting the future in patients with atrial fibrillation: who develops heart failure?

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia; the lifetime risk is 1 in 4 for persons over the age of 55 years in The Netherlands. AF is associated with a five-fold increase in the risk of stroke, a three-fold increase in the risk of heart failure, and a doubling in the risk of dementia and death. Risk prediction models are important to define the individual risk for development of AF. However, in patients who have developed AF, prediction of AF-related complications is also of great clinical importance. Risk prediction schemes are useful for risk communication, patient motivation, and clinical decision-making. The best examples are the stroke risk schemes developed and validated to predict embolic stroke, of which the CHA2DS2-VASc score currently is the most widely used. Based on the CHA2DS2-VASc score, the guidelines recommend the use of oral anticoagulation in patients with (a history of) AF, to prevent future stroke. Despite the success of stroke risk schemes, these schemes only predict one deleterious complication of AF. The EuroHeart Survey investigators proposed a more general risk scheme, which attempts to predict the progressive nature of AF, from paroxysmal to permanent AF, and progression of AF led to more adverse cardiovascular events and hospital admissions. The HATCH scoring system calculates 1 point for hypertension, age ≥ 75 years, and COPD, and 2 points for transient ischaemic attack or stroke, and heart failure, and allows instant classification of the risk of progression to persistent or permanent AF in patients with paroxysmal AF. However, this risk score has not been validated in independent cohorts, and has not found its way into daily clinical practice yet. Until very recently, no risk schemes were available to predict the development of heart failure in patients with AF. In September 2012, Suzuki et al. proposed the H2ARDD risk score (heart diseases 1⁄4 2 points, anaemia 1⁄4 1 point, renal dysfunction 1⁄4 1 point, diabetes 1⁄4 1 point, and diuretic use 1⁄4 1 point; range 0–6 points) to predict heart failure in patients with AF. This score had an excellent discriminative c-statistic of 0.84 in their single hospital-based cohort consisting of 1942 Japanese AF patients. In the present issue of the journal, the results of an analysis in the Belgrade Atrial Fibrillation Study were presented. The authors included a cohort of 842 patients with new-onset AF with structurally normal hearts and investigated risk factors for the development of heart failure. During 5 years of follow-up, 83 AF patients developed heart failure, with a linearized rate of incident heart failure of 0.97% (95% confidence interval 0.78–1.19%) per 100 patient-years. Several covariates were associated with an increased risk of heart failure: a history of hypertension, diabetes mellitus, dilated left atrium (defined as left atrial diameter .40 mm), and low-normal LVEF (defined as LVEF 50– 54%). In addition, the authors found that AF patients who developed heart failure were also at increased risk for cardiovascular hospitalizations and mortality. This last finding is in accordance with another recent paper published in the journal by Smit et al. which showed that when patients developed first AF and then heart failure they had an impaired prognosis, with increased cardiovascular hospitalizations and mortality rates, although prognosis was even worse when patients developed first heart failure and then AF. As with all observational studies, there are some limitations that need to be considered. First, the authors only included patients with structurally normal hearts, and a LVEF .50% on echocardiography. In addition to questions about the generalizability of results to other AF cohorts, this risk score can only be used after an echocardiography has been performed and may preclude the use of the Belgrade AF risk score outside a hospital setting. In contrast, another heart failure risk score, developed by the Framingham Heart Study investigators, that has also very recently been published in the journal, includes only widely available clinical covariates (age, body mass index, diabetes, significant murmur, electrocardiographic LV hypertrophy, and prevalent myocardial infarction). Secondly, residual and unmeasured confounding needs to be considered. Covariates, and biomarkers (e.g. BNP) that were

Obesity is associated with impaired long-term success of pulmonary vein isolation: a plea for risk factor management before ablation

Aims Obesity is an increasing health problem and is an important risk factor for the development of atrial fibrillation (AF). We investigated the association of body mass index (BMI) on the safety and long-term efficacy of pulmonary vein isolation (PVI) for drug-refractory AF. Methods 414 consecutive patients who underwent transcatheter PVI for AF between 2003 and 2013 were included. Successful PVI was defined as absence of atrial arrhythmia on Holter monitoring or ECG, without and with antiarrhythmic drugs during follow-up. Obesity was defined as BMI≥30 kg/m². Results Mean age was 56±10 years, 316 (76%) were male, 311 (75%) had paroxysmal AF and 111 (27%) were obese. After a mean follow-up of 46±32 months (1590 patient-years), freedom from atrial arrhythmia and antiarrhythmic drugs was significantly lower in patients with obesity compared with non-obese patients (30% vs 46%, respectively, P=0.005, log-rank 0.016). With antiarrhythmic drugs, freedom from atrial arrhythmia was 56% vs 68% (P=0.036). No differences in minor and major adverse events were observed between patients with obesity and non-obese patients (major 6% vs 3%, P=0.105, and minor 5% vs 5%, P=0.512). Sensitivity analyses demonstrated that BMI (as continuous variable) was associated with PVI outcome (HR 1.08, 95% CI 1.02 to 1.14, P=0.012). Conclusion Obesity is associated with reduced efficacy of PVI for drug-refractory AF. No relation between obesity and adverse events was found.