van Isabelle Gelder

Heart failure and atrial fibrillation: current concepts and controversies.

Heart failure and atrial fibrillation are very common, particularly in the elderly. Owing to common risk factors both disorders are often present in the same patient. In addition, there is increasing evidence of a complex, reciprocal relation between heart failure and atrial fibrillation. Thus heart failure may cause atrial fibrillation, with electromechanical feedback and neurohumoral activation playing an important mediating role. In addition, atrial fibrillation may promote heart failure; in particular, when there is an uncontrolled ventricular rate, tachycardiomyopathy may develop and thereby heart failure. Eventually, a vicious circle between heart failure and atrial fibrillation may form, in which neurohumoral activation and subtle derangement of rate control are involved. Treatment should aim at unloading of the heart, adequate control of ventricular rate, and correction of neurohumoral activation. Angiotensin converting enzyme inhibitors may help to achieve these goals. Treatment should also include an attempt to restore sinus rhythm through electrical cardioversion, though appropriate timing of cardioversion is difficult. His bundle ablation may be used to achieve adequate rate control in drug refractory cases.

Alterations in Gene Expression of Proteins Involved in the Calcium Handling in Patients with Atrial Fibrillation

Gene Expression in Human Atrial Fibrillation. Introduction: Atrial fibrillation (AF) leads to a loss of atrial contraction within hours to days. During persistence of AF, cellular dedifferentiation and hypertrophy occur, eventually resulting in degenerative changes and cell death. Abnormalities in the calcium handling in response to tachycardia‐induced intracellular calcium overload play a pivotal role in these processes.

The Effect of Rate Control on Quality of Life in Patients With Permanent Atrial Fibrillation Data From the RACE II (Rate Control Efficacy in Permanent Atrial Fibrillation II) Study

OBJECTIVES The aim of this study was to investigate the influence of rate control on quality of life (QOL). BACKGROUND The RACE II (Rate Control Efficacy in Permanent Atrial Fibrillation II) trial showed that lenient rate control is not inferior to strict rate control in terms of cardiovascular morbidity and mortality. The influence of stringency of rate control on QOL is unknown. METHODS In RACE II, a total of 614 patients with permanent atrial fibrillation (AF) were randomized to lenient (resting heart rate [HR] <110 beats/min) or strict (resting HR <80 beats/min, HR during moderate exercise <110 beats/min) rate control. QOL was assessed in 437 patients using the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) questionnaire, AF severity scale, and Multidimensional Fatigue Inventory-20 (MFI-20) at baseline, 1 year, and end of study. QOL changes were related to patient characteristics. RESULTS Median follow-up was 3 years. Mean age was 68 ± 8 years, and 66% were males. At the end of follow-up, all SF-36 subscales were comparable between both groups. The AF severity scale was similar at baseline and end of study. At baseline and at end of study there were no differences in the MFI-20 subscales between the 2 groups. Symptoms at baseline, younger age, and less severe underlying disease, rather than assigned therapy or heart rate, were associated with QOL improvements. Female sex and cardiovascular endpoints during the study were associated with worsening of QOL. CONCLUSIONS Stringency of heart rate control does not influence QOL. Instead, symptoms, sex, age, and severity of the underlying disease influence QOL. (Rate Control Efficacy in Permanent Atrial Fibrillation; NCT00392613).

Myocardial bridging in a survivor of sudden cardiac near-death: role of intracoronary doppler flow measurements and angiography during dobutamine stress in the clinical evaluation.

Extensive myocardial bridging in the left anterior descending coronary artery was found in a 46 year old survivor of sudden cardiac near-death. Positron emission tomography and dobutamine stress echocardiography revealed ischaemia in the myocardium distal to the bridging. Spasm was excluded as cause of the ischaemia by intracoronary infusion of acetylcholine. Further evaluation of the haemodynamic importance of the bridging using intracoronary Doppler flow velocity measurements revealed an abnormal flow reserve. Dobutamine stress during coronary angiography caused increased mechanical compression during diastole. This was accompanied by multiple premature ventricular contractions. After a debridging operation the flow velocity reserve was normal. The abnormalities found during dobutamine stress had disappeared. Unexpectedly, a spasm was inducible. This may have been due to local oedema or scar formation after the operation. For the evaluation of the haemodynamic importance of myocardial bridging, intracoronary Doppler flow velocity measurements and angiography during dobutamine stress may be helpful in clinical decision making.

Endothelin System in Human Persistent and Paroxysmal Atrial Fibrillation

Endothelin System in Atrial Fibrillation. Introduction: Activation of the endothelin system is an important compensatory mechanism that is activated during left ventricular dysfunction. Whether this system plays a role at the atrial level during atrial fibrillation (AF) has not been examined in detail. The purpose of this study was to investigate mRNA and protein expression levels of the endothelin system in AF patients with and without concomitant underlying valve disease.

Lack of prevention of heart failure by serial electrical cardioversion in patients with persistent atrial fibrillation

OBJECTIVE To investigate the occurrence of heart failure complications, and to identify variables that predict heart failure in patients with (recurrent) persistent atrial fibrillation, treated aggressively with serial electrical cardioversion and antiarrhythmic drugs to maintain sinus rhythm. DESIGN Non-randomised controlled trial; cohort; case series; mean (SD) follow up duration 3.4 (1.6) years. SETTING Tertiary care centre. SUBJECTS Consecutive sampling of 342 patients with persistent atrial fibrillation (defined as > 24 hours duration) considered eligible for electrical cardioversion. INTERVENTIONS Serial electrical cardioversions and serial antiarrhythmic drug treatment, after identification and treatment of underlying cardiovascular disease. MAIN OUTCOME MEASURES heart failure complications: development or progression of heart failure requiring the institution or addition of drug treatment, hospital admission, or death from heart failure. RESULTS Development or progression of heart failure occurred in 38 patients (11%), and 22 patients (6%) died from heart failure. These complications were related to the presence of coronary artery disease (p < 0.001, risk ratio 3.2, 95% confidence interval (CI) 1.6 to 6.5), rheumatic heart disease (p < 0.001, risk ratio 5.0, 95% CI 2.4 to 10.2), cardiomyopathy (p < 0.001, risk ratio 5.0, 95% CI 2.0 to 12.4), atrial fibrillation for < 3 months (p = 0.04, risk ratio 2.0, 95% CI 1.0 to 3.7), and poor exercise tolerance (New York Heart Association class III at inclusion, p < 0.001, risk ratio 3.5, 95% CI 1.9 to 6.7). No heart failure complications were observed in patients with lone atrial fibrillation. CONCLUSIONS Aggressive serial electrical cardioversion does not prevent heart failure complications in patients with persistent atrial fibrillation. These complications are predominantly observed in patients with more severe underlying cardiovascular disease. Randomised comparison with rate control treatment is needed to define the optimal treatment for persistent atrial fibrillation in relation to heart failure.

Routine versus aggressive upstream rhythm control for prevention of early atrial fibrillation in heart failure: background, aims and design of the RACE 3 study.

BackgroundRhythm control for atrial fibrillation (AF) is cumbersome because of its progressive nature caused by structural remodelling. Upstream therapy refers to therapeutic interventions aiming to modify the atrial substrate, leading to prevention of AF.ObjectiveThe Routine versus Aggressive upstream rhythm Control for prevention of Early AF in heart failure (RACE 3) study hypothesises that aggressive upstream rhythm control increases persistence of sinus rhythm compared with conventional rhythm control in patients with early AF and mild-to-moderate early systolic or diastolic heart failure undergoing electrical cardioversion.DesignRACE 3 is a prospective, randomised, open, multinational, multicenter trial. Upstream rhythm control consists of angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, mineralocorticoid receptor antagonists, statins, cardiac rehabilitation therapy, and intensive counselling on dietary restrictions, exercise maintenance, and drug adherence. Conventional rhythm control consists of routine rhythm control therapy without cardiac rehabilitation therapy and intensive counselling. In both arms, every effort is made to keep patients in the rhythm control strategy, and ion channel antiarrhythmic drugs or pulmonary vein ablation may be instituted if AF relapses. Total inclusion will be 250 patients. If upstream therapy proves to be effective in improving maintenance of sinus rhythm, it could become a new approach to rhythm control supporting conventional pharmacological and non-pharmacological rhythm control.

Treatment of atrial fibrillation

Correspondence to: Professor H J G M Crijns, Maastricht University Medical Center, Department of Cardiology, Postbus 5800, 6202 AZ Maastricht, The Netherlands; h.crijns@cardio.azm.nl Atrial fibrillation (AF) is the most common arrhythmia and is associated with substantial morbidity, including heart failure and stroke. AF is often encountered in patients with underlying heart disease such as hypertension, and coronary artery and valvular heart disease. 2 The prevalence of AF increases with age, from 0.5% at age 50–59 years to almost 9% at age 80–89 years. The economic burden of AF has also become increasingly important. A large UK based survey of the costs associated with AF showed an increase from 0.6–1.2% of the total National Health Service budget in 1995 to 0.9–2.4% by 2000. In recent years, the results of large clinical trials have had a major impact on the contemporary management of AF. 2 In addition, novel AF ablation techniques have significantly expanded our treatment arsenal. 4 Despite these developments, management of AF in the individual patient often remains troublesome. In this article we aim to provided an overview of the modern treatment strategies for AF.

Current Treatment Recommendations in Antiarrhythmic Therapy

SummaryOver the past decade, various studies have demonstrated that class I antiarrhythmic drugs should be avoided in patients with heart failure, cardiac ischaemia or a previous myocardial infarction. In contrast, class II drugs (β-blockers) reduce morbidity and may even lower mortality in patients suffering from moderate to severe heart failure. In these patients, careful titration of the drug dosage, frequently during hospital admission, may be necessary.If in the setting of heart failure ventricular arrhythmias are symptomatic and/or sustained, patients can be treated effectively, after appropriate treatment of the underlying disease, with the class III drug amiodarone. Unfortunately, this drug does not lower overall mortality, implying that prophylactic institution of amiodarone is not indicated. Pure class III antiarrhythmic drugs like d-sotalol, ibutilide and dofetilide show a high rate of torsade de pointes. Currently, only ibutilide has been approved for clinically monitored intravenous administration. Class IV drugs, the calcium channel blockers, are still very useful for rate control of atrial fibrillation and conversion or prevention of atrioventricular nodal re-entrant tachycardias and circus movement tachycardias using a (concealed) bypass tract.Finally, an implantable cardioverter defibrillator seems to improve overall survival in patients with life-threatening ventricular arrhythmias. This may imply that an increasing number of patients will be candidates for such a device. However, it will be necessary to await publication of data involving these devices from current ongoing studies.

Left Ventricular Ischemia due to Coronary Stenosis as an Unexpected Treatable Cause of Paroxysmal Atrial Fibrillation

Ischemia‐Related Paroxysmal Atrial Fibrillation. We present a patient with exercise‐induced paroxysmal atrial fibrillation who was eventually scheduled for a Cox‐maze operation due to persistence of his complaints of fatigue, impaired exercise tolerance, and predominantly exercise‐related irregular palpitations despite treatment with several antiarrhythmic drugs. A preoperative exercise stress test without antiarrhythmic or negative chronotropic drugs, however, showed clear evidence of myocardial ischemia. After coronary angioplasty of a significant stenosis in the left anterior descending artery, there was no recurrence of atrial fibrillation during a follow‐up of 7 months.