Marcelle D. Smit

Role of inflammation in early atrial fibrillation recurrence

AIMS Outcome of rhythm control in atrial fibrillation (AF) is still poor due to various mechanisms involved in the initiation and perpetuation of AF. Differences in timing of AF recurrence may depend on different types of mechanisms. The aim of this study was to assess the mechanisms involved in early AF recurrence in patients with short-lasting AF. METHODS AND RESULTS Patients with short-lasting persistent AF undergoing rhythm control (n= 100) were included. Markers of mechanisms involved in the initiation and perpetuation of AF were assessed, including clinical factors, echocardiographic parameters, and biomarkers. Primary endpoint was early AF recurrence (recurrence <1 month). Secondary endpoint was progression to permanent AF. Median total AF history was short: 4.2 months. Early AF recurrences occurred in 30 patients (30%) after a median of 6 (inter-quartile range 2-14) days. Baseline log(2) interleukin (IL)-6 [adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI) 1.0-1.7, P= 0.02] and present or previous smoking (adjusted HR 3.6, 95% CI 1.2-10.9, P= 0.03) were independently associated with early AF recurrence, suggesting that inflammation played an important role in early recurrences. Atrial fibrillation became permanent in 29 patients (29%). Baseline transforming growth factor-β1, left ventricular ejection fraction, and early AF recurrence were independently associated with progression to permanent AF. CONCLUSION In patients with short-lasting AF, early AF recurrence seemed to be associated with inflammation as represented by IL-6. Treatment aimed against inflammation may therefore prevent early AF recurrences, which can improve rhythm control outcome.

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

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.

The importance of whether atrial fibrillation or heart failure develops first

Atrial fibrillation (AF) and heart failure often co‐exist. It is unknown whether the sequence in which AF and heart failure develop is of significance regarding prognosis. We assessed the prognosis of AF patients hospitalized for heart failure based on the timing of AF and heart failure development.

Effect of lenient versus strict rate control on cardiac remodeling in patients with atrial fibrillation data of the RACE II (RAte Control Efficacy in permanent atrial fibrillation II) study

OBJECTIVES The aim of this study was to evaluate echocardiographic remodeling in permanent atrial fibrillation (AF) patients treated with either lenient or strict rate control. BACKGROUND It is unknown whether in permanent AF, lenient rate control is associated with more adverse cardiac remodeling than strict rate control. METHODS Echocardiography was conducted at baseline and at follow-up in 517 patients included in the RACE II (RAte Control Efficacy in permanent atrial fibrillation II) trial. Echocardiographic parameters were compared between patients randomized to lenient rate control (n = 261) or strict rate control (n = 256). RESULTS Baseline echocardiographic parameters were comparable between patients randomized to lenient and strict rate control. Between baseline and follow-up, significant adverse atrial or ventricular remodeling was not observed in either group. There were also no significant differences in atrial and ventricular remodeling between patients who continuously had heart rates between 80 and 110 beats/min and patients who continuously had heart rates <80 beats/min during follow-up. Lenient rate control was not independently associated with changes in echocardiographic parameters: mean adjusted effect on left atrial size was 1.6 mm (p = 0.09) and 1.1 mm on left ventricular end-diastolic diameter (p = 0.23). Instead, female sex was independently associated with adverse remodeling: mean adjusted effect on left atrial size was 2.4 mm (p = 0.02) and 6.5 mm on left ventricular end-diastolic diameter (p < 0.0001). CONCLUSIONS Female sex, not lenient rate control, seemed to be associated with significant adverse cardiac remodeling in patients with permanent AF such as those enrolled in the RACE II study. (RAte Control Efficacy in Permanent Atrial Fibrillation [RACE II]; NCT00392613).

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.

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

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.

Upstream therapy of atrial fibrillation

Failure of current pharmacological therapy for atrial fibrillation in maintaining sinus rhythm may be due to structural atrial remodeling caused by inflammation and fibrosis. Upstream therapy that interferes in the structural remodeling process may be effective in maintaining sinus rhythm. This article reviews upstream therapy in atrial fibrillation. Various prospective and retrospective studies demonstrate that upstream therapy, consisting of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, fish oils, glucocorticoids, or moderate physical activity, is associated with a reduced incidence of new-onset atrial fibrillation (i.e., primary prevention) and with a reduced recurrence of atrial fibrillation (i.e., secondary prevention). Larger clinical trials are required to further elucidate the position of upstream therapy in the primary and secondary prevention of atrial fibrillation.

Myocardial perfusion imaging does not adequately assess the risk of coronary artery disease in patients with atrial fibrillation

AIMS The role of coronary artery disease (CAD) in atrial fibrillation (AF) is poorly investigated. This study investigated the value of myocardial perfusion single-photon emission computed tomography (SPECT) in the assessment of risk of CAD in patients with a history of AF. METHODS AND RESULTS Out of consecutive patients without previous coronary angiogram or history of CAD referred for SPECT, patients with a history of AF (n = 129) were compared with age- and gender-matched controls (n = 124). Primary endpoint was positive SPECT, i.e. unambiguous signs of ischaemia. There was no significant difference with regard to positive SPECT outcome between AF patients and controls (14 patients, 11% vs. 21 patients, 17%; P = 0.16). Coronary angiography (CAG) performed after SPECT demonstrated a higher yield of positive SPECT regarding significant CAD in control patients (10 out of 15 patients, 67%) than in AF patients (2 out of 13 patients, 15%; P = 0.006). CONCLUSION Positive SPECT outcome was similar in patients with AF and in controls. Nevertheless, in AF patients a positive SPECT outcome was less often related to significant CAD in those patients who subsequently underwent CAG. These results emphasize the need for new non-invasive techniques to adequately assess the risk of significant CAD in AF patients.

Targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent atrial fibrillation: Results of the RACE 3 trial

Aims Atrial fibrillation (AF) is a progressive disease. Targeted therapy of underlying conditions refers to interventions aiming to modify risk factors in order to prevent AF. We hypothesised that targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent AF. Methods and results We randomized patients with early persistent AF and mild-to-moderate heart failure (HF) to targeted therapy of underlying conditions or conventional therapy. Both groups received causal treatment of AF and HF, and rhythm control therapy. In the intervention group, on top of that, four therapies were started: (i) mineralocorticoid receptor antagonists (MRAs), (ii) statins, (iii) angiotensin converting enzyme inhibitors and/or receptor blockers, and (iv) cardiac rehabilitation including physical activity, dietary restrictions, and counselling. The primary endpoint was sinus rhythm at 1 year during 7 days of Holter monitoring. Of 245 patients, 119 were randomized to targeted and 126 to conventional therapy. The intervention led to a contrast in MRA (101 [85%] vs. 5 [4%] patients, P < 0.001) and statin use (111 [93%] vs. 61 [48%], P < 0.001). Angiotensin converting enzyme inhibitors/angiotensin receptor blockers were not different. Cardiac rehabilitation was completed in 109 (92%) patients. Underlying conditions were more successfully treated in the intervention group. At 1 year, sinus rhythm was present in 89 (75%) patients in the intervention vs. 79 (63%) in the conventional group (odds ratio 1.765, lower limit of 95% confidence interval 1.021, P = 0.042). Conclusions RACE 3 confirms that targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent AF. Trial Registration number Clinicaltrials.gov NCT00877643.

The value and limitations of a wound inspection clinic after cardiac device implantation

Background: Due to the growing number of cardiac device implantations it is important to develop methods to reduce device-implantation related complications. Aims: To determine whether a wound inspection clinic can play a role in the detection of device-implantation related complications. Methods: Single-center observational study evaluating patients who received a pacemaker or implantable cardioverter-defibrillator (ICD). Results: Of 159 patients who received an appointment for the wound inspection clinic, 52 (33%) received a pacemaker and 107 (67%) received an ICD. The majority had no signs of infection. Pain (n = 13, 8%) and swelling (n = 11, 7%) were the most frequent signs observed, but they never necessitated intervention and recovered spontaneously in all patients. During follow-up (mean 20 ± 9 weeks), complications occurred in 10 patients (6%). Most complications occurred early, within 4 days after implantation. The two late complications (at 19 and 41 days) could not be recognized at the wound inspection clinic. Conclusion: We found no useful role for a wound inspection clinic two weeks post-implant to detect device-related complications. Open rapid access to the pacemaker/ICD center for patients with signs and symptoms of (threatening) complications seems to be more appropriate to manage post-implant patients.