Mechanisms of Action of Active Esophageal Cooling During Left Atrial Radiofrequency Ablation: A Multidisciplinary Review

Purpose: To determine possible mechanisms of action underpinning the protective effects of active esophageal cooling. Active esophageal cooling is increasingly used as a protective strategy during left atrial radiofrequency (RF) ablation for the treatment of atrial fibrillation (AF). Endoscopic data show an 83% reduction in esophageal lesions with active esophageal cooling, but to date, with over 18,000 ablation cases completed with a dedicated esophageal cooling device, there has been no reported atrioesophageal fistula (and only one pericardio-esophageal fistula has been reported). Thus, additional protective mechanisms beyond acute thermal injury reduction from cooling are likely to be involved.

Material and Methods: We reviewed the literature on burn injury progression, fibrosis, fistula formation, and therapeutic hypothermia, focusing on studies that identified molecular factors involved in these processes. Common mediators were cataloged, and the effects of temperature on the activity of these mediators were then determined from additional literature searches.

Results: We identified more than 135 relevant articles and found that a wide range of molecular mediators are implicated in the pathophysiology of burn injury progression, fibrosis, and fistula development. Both fibrosis and epithelial-to-mesenchymal transition (EMT) are potential drivers of fistula development after an initial thermal injury. The soluble mediators of these processes are also implicated in burn wound conversion, which further facilitates progression of a thermal injury. Importantly, the activity of many pro-inflammatory markers have been shown to be inhibited by cooling, while some anti-inflammatory mediators are activated.

Conclusions: Thermal injury triggers an inflammatory cascade that may result in further progression of the injury, leading to fibrosis and fistula formation. Cooling affects the activity of a majority of the molecular mediators of this inflammatory cascade. This may explain the safety benefits seen clinically with active esophageal cooling and suggests an important direction for further investigation.