Pathophysiology and Treatment Modalities for Atrial Fibrillation: Present and Future

Atrial fibrillation (AF) is most common sustained clinical cardiac arrhythmias. Although it is not usually life-threatening, it is a serious condition and may contribute to morbidity and mortality. Untreated AF elevates the risk of stroke, heart failure, systemic embolism, and ventricular dysfunction. This thematic issue covers the recent developments in epidemiology, pathophysiology, diagnosis, and treatment modalities of AF and future directions. There are nine articles related to this thematic issue.

Nayak et al summarizes the epidemiology, major risk factors, and their role in the pathogenesis of AF.

Prasad in his article, entitled “AGE-RAGE Stress in the Pathogenesis of Atrial Fibrillation and a New Paradigm for its Treatment,” discusses the role of AGE (advanced glycation end products)-RAGE (receptor for AGE) stress in the pathogenesis of AF and its treatment. AGE -RAGE stress is defined as a shift in the balance between stressors (AGE and RAGE) and antistressor (soluble receptor for AGE [sRAGE]) in favor of stressors. The ratio of AGE/sRAGE has been proposed as a measure of AGE-RAGE stress in clinical practice. Serum levels in AGE, sRAGE and expression of RAGE have reported to be elevated in patients with AF. However, these parameters were not measured simultaneously in the same patients. Although both AGE and sRAGE are elevated in AF, the elevation may be greater in AGE as compared with sRAGE, hence AGE-RAGE stress will be high. The treatment has been suggested to be targeted at reduction of AGE and RAGE, blocking of RAGE binding to AGE, decreasing expression of RAGE, elevation of sRAGE, and reduction in oxidative stress. Involvement of AGE-RAGE stress in the pathogenesis of AF is a novel idea and its treatment is a new paradigm.

The article by Dharma on “Double Antithrombotic versus Triple Antithrombotic Therapy in Patients with Atrial Fibrillation (AF) and Acute Coronary Syndrome (ACS)” dealt with the antithrombotic treatment in AF. He described that dual antiplatelet therapy (DAPT) with aspirin and A₂Y₁₂ inhibitor in patients with ACS treated with percutaneous coronary intervention (PCI) reduces major cardiac events and stent thrombosis. Administration of a combination of oral anticoagulants and DAPT in PCI treated ACS patients with AF improves the outcome but increases the risk of bleeding. A meta-analysis of clinical trials have shown that there is a reduction in bleeding with DAPT as compared with combined use of oral anticoagulants and DAPT. Currently there is no established consensus or guidelines for appropriate combinations of antithrombotic agents for treatment of AF in ACS patients treated with PCI.

Santoso has provided an excellent review on “Direct Oral Anticoagulants plus Single Antiplatelet versus Standard Triple Therapy in Nonvalvular Atrial Fibrillation and Acute Coronary Syndrome—Coronary Artery Disease: Stroke Prevention in Asian Population.” He addresses the clinical dilemma in the use of DAPT and direct oral anticoagulant (DOAC) therapy. He compares different scoring systems that predicts the bleeding risk among patients with AF. For the majority of patients, triple therapy comprising of DOAC, aspirin, and clopidogrel should be considered for 1 to 6 months, following percutaneous coronary intervention in patients with ACS. The optimal duration of triple therapy should depend on patient's ischemic and bleeding risks.

Mattia et al provides an exceptional review on catheter-based and surgical treatment of AF and the treatment of surgical based complications (incomplete ablation lines, atrial flutter, heart block, and bleeding) and catheter ablation–based complications (pulmonary vein stenosis, cardiac tamponade, persistent atrial septal defect, and atrial–esophageal fistula).

Hesselson's review on catheter ablation (CA), discusses the studies of CA and contemporary issues related to ablation targets in detail, and gives some futuristic view on the use of CA in AF. Ablation of pulmonary veins and pulmonary vein isolation (PVI) ablation are being used for the treatment of AF. The success rate is high for PVI ablation, especially in persistent AF. Posterior isolation is most prevalent for ablation. Numerous modes of energy applications are available to perform ablation with radiofrequency and cryoablation being the most common. Technological advances will result in improved outcome for the treatment of AF.

Riedlbauchova et al have provided a very good and extensive review on “Nonpharmacological Treatment of Atrial Fibrillation (AF).” This review describes the role of pacemaker, implantable cardioverter-defibrillator, and cardiac resynchronization therapy in the prevention and treatment of AF. Implantable devices also serve as permanent echocardiogram (ECG) monitors that provide information of presence and the characteristic of AF and can help in modifying the therapeutic approach for stroke prevention.

The article of Gunn et al, entitled “Contemporary Surgical Management of Atrial Fibrillation (AF),” discusses the indications, treatments, outcomes, surgical techniques, and surgical treatment of AF. He concludes that catheter and surgical ablation are commonly used in the treatment of AF. The benefits of surgical ablation as a concomitant stand alone or hybrid procedure for AF are now becoming better understood. There will be a continued optimization of identified ablation lesion sets with a better understanding of the mechanisms of AF. Increased cooperation between electrophysiologists and surgeons will help in the advancement of surgical treatment for AF.

Natrajan et al have described in detail the role of CA in the treatment of AF in structurally normal hearts, patients with heart failure, and special populations (extreme-age patients who are older than 80 years, hypertrophic cardiomyopathy, presence of accessory pathway, athletes, and congenital heart disease). CA is relatively safe and has proven benefits in alleviating symptoms and improving the quality of life in patients with symptomatic paroxysmal and persistent AF. CA helps a heterogeneous group of patients with AF. The success of CA procedures depends upon AF chronicity, comorbid conditions, and experienced centers with high volumes. A detailed description of the use of antiarrhythmic drugs for treatment of AF has been also provided. Long-term success rate with CA is better than antiarrhythmic drugs.

We sincerely thank the contributors for submitting excellent papers and the reviewers for their time in reviewing these papers. Our special thanks to Denise M. Rossignol, the managing editor for the International Journal of Angiology for her assistance in preparation of this thematic issue.