Mechanisms of action behind the protective effects of proactive esophageal cooling during radiofrequency catheter ablation in the left atrium

Abstract

Proactive esophageal cooling for the purpose of reducing the likelihood of ablation-related esophageal injury resulting from radiofrequency (RF) cardiac ablation procedures is increasingly being used and has been Food and Drug Administration cleared as a protective strategy during left atrial RF ablation for the treatment of atrial fibrillation. In this review, we examine the evidence supporting the use of proactive esophageal cooling and the potential mechanisms of action that reduce the likelihood of atrioesophageal fistula (AEF) formation. Although the pathophysiology behind AEF formation after thermal injury from RF ablation is not well studied, a robust literature on fistula formation in other conditions (eg, Crohn disease, cancer, and trauma) exists and the relationship to AEF formation is investigated in this review. Likewise, we examine the abundant data in the surgical literature on burn and thermal injury progression as well as the acute and chronic mitigating effects of cooling. We discuss the relationship of these data and maladaptive healing mechanisms to the well-recognized postablation pathophysiological effects after RF ablation. Finally, we review additional important considerations such as patient selection, clinical workflow, and implementation strategies for proactive esophageal cooling.

Keywords: Atrial fibrillation; Atrioesophageal fistula; Esophageal cooling; Pulmonary vein isolation; Radiofrequency ablation.

Graphical abstract

Figure 1

Transmurality of lesions at varying ranges of power, duration, and cooling water temperature using a dedicated active esophageal cooling device in an animal model with ablation procedures directly on the esophagus. Findings in the animal model (orange bars) are compared with results predicted from mathematical modeling (blue bars) discussed further below. Reproduced from Montoya, et al.

Figure 2

A: Physical situation modeled with a proactive cooling device located in the esophageal lumen. B: Model geometry including RF catheter, tissues near the ablation site, and proactive cooling device located in the esophageal lumen. The evaluation line (black line) for postprocessing is shown across the ablated tissues, from the tip of the RF catheter to the edge of the active cooling device. Reproduced from Montoya, et al. 3D = 3-dimensional; RF = radiofrequency.

Figure 3

Lesion shapes for 50 W/10 s and 90 W/4 s ablation procedures, with (protection) and without (control) proactive esophageal cooling. Left-sided images show the case after the RF pulse and right-sided images show the case after 90 seconds, allowing for the effects of thermal latency. Thermal injury is not seen in the fat layer since the fraction of damage incurred by fat is lower than that of myocardial or esophageal tissue, which is a consequence of tissue parameters incorporated into the Arrhenius equation reflecting relative resistance of adipocytes to thermal insult. Reproduced from Montoya, et al. RF = radiofrequency.

Figure 4

Dose-response relationship between the duration of cooling and the probability of a full thickness depth of burn. A significant inverse relation is observed between the duration of cooling and the probability of full thickness depth. Relative to burns that failed to receive any first aid cooling, those cooled with running water for lengths of ≥5 minutes had a significantly reduced probability of classification as full thickness, with progressively greater probability reductions in the 5- to 10-minute (OR 0.3; 95% CI 0.1–1.0; P = .04), 11- to 19-minute (OR 0.3; 95% CI 0.1–0.9; P = .03), and ≥20-minute (OR 0.2; 95% CI 0.1–0.4; P < .001) groups. Reproduced from Griffin, et al., with permission. CI = confidence interval; OR = odds ratio.

Figure 5

Pathogenesis of Crohn disease–associated fistulae. After an epithelial barrier defect in the gastrointestinal tract (such as would occur in the esophagus after thermal injury) several PAMPs, for example, MDP, are able to enter the gut mucosa. Both the process of wound repair (A) and the inflammatory response caused by PAMPs (B) induce the event of EMT. First, an increased expression of TNF is initiated (C), resulting in an upregulation of TGF-β production. This triggers the expression and secretion of IL-13 as well as of molecules associated with cell invasiveness, such as β6-integrin (D). The enhanced activity of MMPs, as well as the upregulation of protein expression, favors the transformation of the IECs toward the invasive myofibroblast forms, which finally results in fistula formation (E). Reproduced from Scharl, et al. EMT = epithelial-to- mesenchymal transition; IEC = intestinal epithelial cell; IL-13 = interleukin 13; MDP = muramyl dipeptide; MMP = membrane metalloproteinase; PAMP = pathogen-associated molecular patterns; TGF-β = tumor growth factor β; TNF = tumor necrosis factor.

Figure 6

Example heat exchanger, connector tubing, and esophageal cooling device.

Figure 7

A: Visualization of the proactive esophageal cooling device (ensoETM, Attune Medical, Chicago, IL) on fluoroscopy, showing the radiopaque tip below the diaphragm. B: Visualization of the proactive esophageal cooling device (ensoETM, Attune Medical) on intracardiac echocardiography, showing anterior and posterior borders of the device in the esophagus.