The COMBINE-AF Trial

Atrial fibrillation (AF), often called AFib, is the most common type of irregular heartbeat. Normally, the heart beats in a steady rhythm. In AF, the upper chambers of the heart (the atria) beat very fast and irregularly, which prevents blood from being pumped out completely. People with AF may feel heart palpitations (a racing or fluttering feeling), dizziness, shortness of breath, fatigue, and chest discomfort. Over time, AF increases the risk of blood clots, stroke, heart failure, and other serious health problems.

What is long-standing persistent AF?

AF is classified by how long it lasts. This study focuses on long-standing persistent AF, which is defined as continuous AF that lasts for more than 12 months. In this form of AF, the heart's upper chambers have undergone significant changes-often called "atrial remodeling." These changes make the heart tissue more prone to sustaining irregular rhythms and make the condition harder to treat compared to shorter-lasting forms of AF. Many patients with long-standing persistent AF continue to have symptoms even after trying antiarrhythmic medications (drugs designed to control heart rhythm), and finding an effective treatment remains a challenge.

Why is this study needed?

Catheter ablation is a procedure that uses energy to create small scars in specific areas of the heart to block abnormal electrical signals. Pulmonary vein isolation (PVI) is the standard ablation procedure for AF, where the doctor isolates the areas where most abnormal signals start. However, in patients with long-standing persistent AF, PVI alone is often not enough. Studies show that only about half of patients remain in normal heart rhythm 12 months after PVI alone. Researchers believe that additional ablation lines-created along specific pathways outside the pulmonary veins-may help block more abnormal electrical circuits and improve outcomes. The main challenge is that doctors do not yet know which combination of ablation lines works best.

Newer energy technologies may also help. Pulsed field ablation (PFA) is a new, non-thermal ablation technology that uses short, high-voltage electrical pulses to kill heart cells that cause abnormal signals. Unlike traditional heat-based methods (such as radiofrequency ablation), PFA is more selective. It targets heart tissue while causing less damage to nearby structures like the esophagus (the tube connecting the throat to the stomach) and the phrenic nerves (which control breathing). This makes PFA potentially safer for treating areas near these sensitive structures. Radiofrequency (RF) ablation uses heat and remains a reliable method for creating precise, targeted lesions. This study combines both technologies: PFA for isolating the pulmonary veins and the back wall of the left atrium, and RF for creating additional linear lesions.