Showing papers by "Isabelle C. Van Gelder published in 2011"

Corrigendum to: ‘Guidelines for the management of atrial fibrillation’ [European Heart Journal (2010) 31, 2369–2429 and EP-Europace (2010) 12, 1360–1420]

Abstract: The European Society of Cardiology and the publishers regret that a table containing errors was published in these guidelines. Table 15 (page 2399 in …

Mechanisms of atrial structural changes caused by stretch occurring before and during early atrial fibrillation.

Abstract: Structural remodelling occurring before, due to the underlying heart disease, and during atrial fibrillation (AF) sets the stage for permanent AF. Current therapy in AF aims to maintain sinus rhythm in symptomatic patients, but outcome is unfortunately poor. Stretch of the atria is a main contributor to atrial remodelling. In this review, we describe different aspects of structural remodelling as seen in animal models and in patients with AF, including atrial enlargement, cellular hypertrophy, dedifferentiation, fibrosis, apoptosis, and loss of contractile elements. In the second part, we describe downstream signals of mechanical stretch and their contribution to AF and structural remodelling. Ultimately, knowledge of mechanisms underlying structural remodelling may help to identify new pharmacological targets for AF prevention.

Clinical and prognostic effects of atrial fibrillation in heart failure patients with reduced and preserved left ventricular ejection fraction

Abstract: AIMS: Atrial fibrillation (AF) is common in heart failure (HF), but few data regarding the prognostic relevance of AF are available in HF patients with preserved left ventricular ejection fraction (HF-PEF). We aimed to study the clinical impact of AF vs. sinus rhythm (SR) in stabilized HF patients with reduced left ventricular ejection fraction (HF-REF) and in those with preserved left ventricular ejection fraction (HF-PEF). METHODS AND RESULTS: We studied 927 patients with stable HF, of whom 336 (36%) had AF. N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations were measured at baseline and patients were followed for 18 months. We compared time to first HF (re-)hospitalization or death between patients with AF and SR. Atrial fibrillation was present at baseline in 215 (35%) patients with HF-REF (mean LVEF 0.25 + 0.08) and in 121 (40%) patients with HF-PEF (mean LVEF 0.50 + 0.09). Plasma NT-proBNP levels were similar in AF and SR patients (median 2398 vs. 2532 pg/mL, P = 0.74). Atrial fibrillation was independently associated with elevated NT-proBNP levels in HF-PEF, but not in HF-REF patients (multivariable B = 0.33, P= 0.047 and B = 0.03; P = 0.89, respectively). After 18 months of follow-up, the presence of AF was an independent predictor of death or HF hospitalization in HF-PEF (multivariable hazard ratio 1.49 (95% CI 1.04-2.14), P = 0.03), but not in HF-REF patients (1.05 (CI 95% 0.80-1.38), P = 0.72). CONCLUSION: Atrial fibrillation is equally common in patients with HF-PEF and HF-REF. In HF-PEF, but not in HF-REF patients, AF was associated with higher NT-proBNP levels and was independently related to death or HF hospitalization.

HSPB1, HSPB6, HSPB7 and HSPB8 protect against RhoA GTPase-induced remodeling in tachypaced atrial myocytes.

Abstract: Background We previously demonstrated the small heat shock protein, HSPB1, to prevent tachycardia remodeling in in vitro and in vivo models for Atrial Fibrillation (AF). To gain insight into its mechanism of action, we examined the protective effect of all 10 members of the HSPB family on tachycardia remodeling. Furthermore, modulating effects of HSPB on RhoA GTPase activity and F-actin stress fiber formation were examined, as this pathway was found of prime importance in tachycardia remodeling events and the initiation of AF. Methods and Results Tachypacing (4 Hz) of HL-1 atrial myocytes significantly and progressively reduced the amplitude of Ca2+ transients (CaT). In addition to HSPB1, also overexpression of HSPB6, HSPB7 and HSPB8 protected against tachypacing-induced CaT reduction. The protective effect was independent of HSPB1. Moreover, tachypacing induced RhoA GTPase activity and caused F-actin stress fiber formation. The ROCK inhibitor Y27632 significantly prevented tachypacing-induced F-actin formation and CaT reductions, showing that RhoA activation is required for remodeling. Although all protective HSPB members prevented the formation of F-actin stress fibers, their mode of action differs. Whilst HSPB1, HSPB6 and HSPB7 acted via direct prevention of F-actin formation, HSPB8-protection was mediated via inhibition of RhoA GTPase activity. Conclusion Overexpression of HSPB1, as well as HSPB6, HSPB7 and HSPB8 independently protect against tachycardia remodeling by attenuation of the RhoA GTPase pathway at different levels. The cardioprotective role for multiple HSPB members indicate a possible therapeutic benefit of compounds able to boost the expression of single or multiple members of the HSPB family.

Comprehensive risk reduction in patients with atrial fibrillation: Emerging diagnostic and therapeutic options Executive summary* of the report from the 3rd AFNET/EHRA consensus conference

Abstract: There are exciting new developments in several areas of atrial fibrillation (AF) management that carry the hope of improving outcomes in AF patients. This paper is an executive summary that summarises the proceedings from the 3rd AFNET/EHRA consensus conference on atrial fibrillation, held in Sophia Antipolis from November 7th to 9th 2010, shortly after the release of the new ESC guidelines on AF. The conference was jointly organised by the German Atrial Fibrillation competence NETwork (AFNET) and the European Heart Rhythm Association (EHRA). This executive summary report covers four sections: 1. Risk factors and risk markers for AF, 2. Pathophysiological classification of AF, 3. Relevance of monitored AF duration for AF-related outcomes, and 4. Perspectives and needs for implementing better antithrombotic therapy.

Determinants and outcome of amiodarone‐associated thyroid dysfunction

Abstract: Summary Objective Amiodarone is frequently associated with thyroid dysfunction. Identifying predictors for amiodarone-associated thyroid dysfunction and assessing treatment outcome may aid clinicians in daily practice. Methods We included 303 consecutive patients with amiodarone therapy for cardiac arrhythmias (260 with atrial fibrillation and 43 with ventricular arrhythmias). Thyroid function tests were performed every 6 months. Results Mean age was 63 ± 12 years and 66% was male. After median follow-up of 3·3 (0·1–24) years, 23 (8%) patients developed amiodarone-associated thyrotoxicosis (incidence rate 1·9 per 100 person years) and 18 (6%) hypothyroidism (incidence rate 1·1 per 100 person years). The only predictor for amiodarone-associated thyrotoxicosis was age 1·4 mU/l at baseline [HR = 5·1 (95% CI 1·1–22·4), P = 0·03], left ventricular ejection fraction <45% [HR = 3·8 (95% CI 1·1–13·3), P = 0·04] and diabetes mellitus at baseline [HR = 3·3 (95% CI 1·1–10·3), P = 0·04]. Gender was not a predictor for amiodarone-associated thyroid dysfunction. Five out of 12 (42%) patients with thyrotoxicosis exhibited spontaneous normalization of thyroid function on continuation of amiodarone therapy. Mean time to normalization in the total group was 6·2 ± 3·3 months, with no difference between continuing or discontinuing amiodarone (6·6 ± 3·8 vs 5·8 ± 2·8 months, P = 0·5). Conclusions During median follow-up of 3·3 years, the incidence of amiodarone-associated thyrotoxicosis was higher compared to hypothyroidism. Only general predictors for amiodarone-associated thyroid dysfunction were observed. Discontinuation of amiodarone did not influence treatment outcome.

Rationale and current perspective for early rhythm control therapy in atrial fibrillation

Abstract: Atrial fibrillation (AF) is the most common sustained arrhythmia and an important source for mortality and morbidity on a population level. Despite the clear association between AF and death, stroke, and other cardiovascular events, there is no evidence that rhythm control treatment improves outcome in AF patients. The poor outcome of rhythm control relates to the severity of the atrial substrate for AF not only due to the underlying atrial remodelling process but also due to the poor efficacy and adverse events of the currently available ion-channel antiarrhythmic drugs and ablation techniques. Data suggest, however, an association between sinus rhythm maintenance and improved survival. Hypothetically, sinus rhythm may also lead to a lower risk of stroke and heart failure. The presence of AF, thus, seems one of the modifiable factors associated with death and cardiovascular morbidity in AF patients. Patients with a short history of AF and the underlying heart disease have not been studied before. It is fair to assume that abolishment of AF in these patients is more successful and possibly also safer, which could translate into a prognostic benefit of early rhythm control therapy. Several trials are now investigating whether aggressive early rhythm control therapy can reduce cardiovascular morbidity and mortality and increase maintenance of sinus rhythm. In the present paper we describe the background of these studies and provide some information on their design.

Prognostic importance of natriuretic peptides and atrial fibrillation in patients receiving cardiac resynchronization therapy

Abstract: Aims The aim of this study was to investigate the prognostic value of natriuretic peptides and atrial fibrillation (AF) on response to cardiac resynchronization therapy (CRT) and mortality. Methods and results This study included 338 consecutive CRT patients. Response to CRT was defined as a reduction in left ventricular end-systolic volume of ≥15% in the absence of death at 6-month follow-up. During follow-up (27 ± 19 months), 139 patients (41%) had AF, being new onset in 40 patients (21%). Forty-two patients (12%) had permanent AF. Response to CRT was observed in 168 of 302 patients (56%): 60 of 123 patients (43%) with AF vs. 108 of 179 patients (60%) without AF (P = 0.047). Low baseline atrial natriuretic peptide (ANP) [odds ratio for log2 ANP 0.49, 95% confidence interval (CI) 0.35–0.68, P < 0.001] and large left ventricular end-systolic volume (odds ratio for every 50 mL 1.40, 95% CI 1.09–1.79, P = 0.009) were independent predictors of response. Neither the presence of AF nor the increase in AF burden independently predicted response. Ninety patients (27%) died; 50 patients (36%) with AF vs. 40 patients (20%) without AF (log rank P = 0.029). Important predictors of all-cause mortality were new-onset AF (hazard ratio 8.11, 95% CI 3.31–19.85, P < 0.001), permanent AF (hazard ratio 3.19, 95% CI 1.61–6.30, P = 0.001), and baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) (hazard ratio for log2 NT-proBNP 0.77, 95% CI 0.66–0.90, P = 0.001). Conclusion In patients treated with CRT, lower ANP and larger left ventricular end-systolic volume were independent predictors of response. New-onset AF, permanent AF, and NT-proBNP were independently associated with increased all-cause mortality.

New treatment options for atrial fibrillation: towards patient tailored therapy

Abstract: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Currently more than six million people in Europe are affected by AF and this number is expected to increase twofold during the next 30–50 years, partly due to the ageing population.1 AF is not a benign disease as it is responsible for an increased risk of death, stroke, and heart failure, reduced exercise capacity and left ventricular dysfunction, and an impaired quality of life. It is therefore important to develop safe treatment strategies for AF in order to improve outcome and to promote healthy ageing. Treatment of AF, however, is not straightforward due to the progressive nature of the arrhythmia, the wide range of associated diseases, and differences in presentation between patients. The complexity of the ‘syndrome’ requires that AF treatment should be tailored to the individual patient. The purpose of this article is to review new treatment options for AF to optimise patient tailored therapy, in the context of the natural time course and complexity of AF, and with the main focus on rhythm control. AF has a multifactorial aetiology, the pathophysiology of AF being complex and incompletely understood. Over the past years the role of structural remodelling in the initiation and perpetuation of AF has increasingly become apparent. Structural remodelling can be caused by: well known risk factors of AF development such as age, hypertension, heart failure, valve disease, and diabetes; less well known risk factors such as endurance training, obesity, sleep apnoea syndrome, and chronic obstructive pulmonary disease; and other factors such as altered metabolism, autonomic changes, and genetic and environmental influences.1 2 These factors induce atrial structural changes through various pathways including the renin–angiotensin–aldosterone system (RAAS) and inflammation, leading to enlarged atria, …