Short summary

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It often appears with other predisposing cardiovascular diseases. In the management of AF, the use of Maze IV surgery has been increasing since 2002. There are a few studies investigating the effect of a concomitant Maze IV procedure in patients with AF scheduled for heart surgery, which show promising results, but the overriding evidence, especially long-term results, is limited. No prolonged follow-up has been done in these patients and, therefore, the significance of factors predicting late AF recurrence is limited. The limitation of these predictors is further increased by a discrepancy in the pre-existing results between pre- and postoperative predictors of late AF recurrence. Therefore, Further investigations with long-term follow-up are needed.

Rationale

The incidence and prevalence of AF are exponentially increasing worldwide, more frequently affecting men and elderly. This fact constitutes a future major burden for the health care system in the next decades along with the similarly extending life expectancy and the fact that a huge hidden group of asymptomatic and transient subtypes of the arrhythmia (i.e. paroxysmal AF) may underestimate the AF prevalence. A group of these patients may be resistant to standard medical therapy. In those cases surgical AF treatment might be a reasonable option. The technique is often performed as concomitant procedure in patients with AF, who undergo cardiac surgery for another cardiovascular disease. One of these procedures is the Cox-Maze IV technique from 2002. It is a biatrial "cut-and-sew" procedure, which aims to surgically create a "maze" of functional atrial myocardium via atrial incisions that obstruct all potential points of re-entry. To ensure transmurality all around the atria, the atrial tissue around the orifices (i.e. coronary sinus, tricuspid valve and mitral valve) is also treated with cryoablation.

The use of Maze IV surgery in patients with AF has been increasing, but only a few studies have investigated the effect of concomitant Maze IV surgery. They all show promising results with 84-89% of patients maintaining sinus rhythm after 12 months, but the long-term efficacy of the surgical intervention is still insufficiently described.

Thereby, the aim of this study is to investigate the long-term efficacy of concomitant Maze IV surgery in patients with AF during a 6-year follow-up. The effect of the surgical procedure will be defined as maintaining sinus rhythm while off antiarrhythmic drugs (AADs). In addition, possible predictors for late AF recurrence will be analysed. The analysis includes comparison of preoperative AF subtype, comorbidity and echocardiographically estimated left atrial size and the following effect of the concomitant Maze IV surgery. Furthermore, the effect of postoperative risk factors, such as electrocardiographically documented ATAs, on the long-term result of the surgical treatment will be analysed. The associated changes in AF symptoms before the surgical intervention, afterwards and at the follow-up examination will be elucidated by specific questionnaires.

The results of this study will provide further insight into the practicability of Maze IV surgery in patients with different preoperative AF subtypes and possible comorbidities, as well as useful knowledge with regard to pre- and postoperative predictors of late AF recurrence. Finally, our results will contribute to the common agreement of the clinical treatment algorithm for AF including Maze IV surgery as a potential option.

Description of the cohort

In this retrospective cohort study with long-term follow-up we investigate 164 consecutive patients with diagnosed AF, who underwent Maze-IV operation from 2006-2010 at Odense University Hospital (OUH). In all cases the procedure was combined with other cardiac surgery, 19% having more than 2 procedures. All patients will be invited to participate in the follow-up investigation, which includes history, physical examination, medication, ECG and 48-hours Holter-monitoring.

Inclusion criteria

• Patients diagnosed with AF documented by a preoperative Holter-monitor or ECG.
• Patients, who have received a Maze IV procedure as a part of the treatment strategy of AF and as adjunctive therapy to cardiac surgery due to another cardiovascular disease.

Data and biological material

The follow-up session will be performed after oral and written informed consent. Data regarding age, gender, medical history and dispositions including conventional risk factors will be collected. At the hospital session the history will focus on the patient's general well-being, symptomatology and present as well as previous AF-related diseases. Symptoms will be evaluated by specific questionnaires (AFEQT, EQ-5D, AF-6). The physical examination includes evaluation of the patient's current general condition and measuring of the vital parameters such as blood pressure and heart rate. Furthermore an ECG and 48-hours Holter-monitoring will be performed.

The primary endpoint is freedom from AF, atrial tachycardia or atrial flutter (i.e. atrial tachyarrhythmias, ATAs) with duration of > 30 s after the procedure while off AADs. Secondary endpoints are freedom from

ATAs on antiarrhythmic drugs, stroke, catheter ablation procedures and pacemaker/ICD implantations and all-cause as well as cardiovascular mortality during follow-up.

Further information regarding the primary and secondary endpoints in patients, who died during follow-up, will be collected from the following registries:

• The Danish National Hospital Register (LPR)
• The Danish Register on mortality causes (The Danish Health Data Agency)
• Vestdansk Hjertedatabase
• Odense Pharmacoepidemiological Database (OPED).

Collaborating researchers and departments

Department of Cardiology, Odense University Hospital

• Associate Professor Axel Brandes, MD, DMSc
• Kenneth Pedersen, MD

Department of Thoracic Surgery, Odense University Hospital

• Peter Appel Pallesen, MD
• Lars Riber, MD, PhD