Key Points
- •
Esophageal ulceration after atrial fibrillation (AF) ablation is associated with transmural atrial and esophageal necrosis with all energy sources, such as radiofrequency (RF), high-intensity focused ultrasound (HIFU), and cryoablation.
- •
The size of esophageal ulceration is significantly related to the maximum luminal esophageal temperature (LET) for RF energy and HIFU and the minimum LET for cryoablation, indicating thermal injury as a mechanism of esophageal injury (ulceration) during AF ablation.
- •
In the canine studies, there is a steep gradient of LET, such that the highest LET (RF and HIFU) or lowest LET (cryoablation) is recorded in only a very small area, suggesting that the small area of highest (or lowest) LET would usually be missed by a single thermocouple within the esophagus as used in clinical settings.
- •
In the canine model, progression of esophageal ulcer size and the development of left atrial–esophageal fistulae are associated with reflux esophagitis and relaxation of the gastroesophageal sphincter, which might be the result of damage to the periesophageal vagal plexus during ablation.
Esophageal injury, manifested as esophageal perforation or left atrial-esophageal fistula, has been reported after catheter or surgical ablation of atrial fibrillation (AF) using unipolar radiofrequency (RF) current and after catheter ablation using high-intensity focused ultrasound (HIFU). Left atrial-esophageal fistula is associated with a high morbidity and mortality, including air embolism and sepsis. Although esophageal perforation and left atrial-esophageal fistula are rare, injury to the esophagus is common after AF ablation. In several clinical studies, endoscopy performed 1 to 3 days after AF ablation identified an asymptomatic esophageal ulcer (directly behind the left atrium) in 4% to 57% patients.
Esophageal injury during AF ablation is thought to result from thermal injury. Cryoablation has been postulated to have a lower risk for esophageal injury for AF ablation. We developed a canine model to study the factors and time course of esophageal injury after ablation in the left atrium close to the esophagus, simulating AF ablation. This model allows a comparison of propensity for esophageal injury between different forms of ablation energy.
Esophageal Injury after Ablation with Ultrasound Energy
This canine model was initially used to explore the factors leading to esophageal injury and left atrial-esophageal fistula after ablation using ultrasound energy (HIFU forward-firing balloon or side-firing unfocused ultrasound balloon; ProRhythm, Ronkonkoma, NY). In 20 closed-chest anesthetized dogs, the ultrasound balloon ablation catheter was positioned at the posterior left atrium (or within the pulmonary vein) directly opposite an air-filled balloon (diameter, 2.5 cm) in the esophagus. This esophageal balloon was designed to both push the esophagus toward the posterior left atrium (mimicking the clinical situation with the esophagus positioned against the left atrium) and accurately record the maximum luminal esophageal temperature during ablation, using seven closely spaced thermocouples (2-mm separation) on the surface of the balloon facing the left atrium ( Figures 4–1 and 4–2 ). The ablation catheter was positioned in the left atrium or pulmonary vein to deliver energy as close as possible to the thermocouples on the esophageal balloon (see Figure 4–1 ). The luminal esophageal temperature was recorded from the balloon thermocouples while ultrasound energy was delivered. To identify the presence or absence of esophageal injury, we performed esophageal endoscopy before ablation, immediately after ablation, and 1 to 4 weeks after ablation. Endoscopic findings were correlated with histologic examination.
An esophageal ulcer was identified by endoscopy within minutes after ablation in 18 of the 20 dogs. All ulcers were associated with the maximum luminal esophageal temperature ≥50°C ( Figures 4–3 and 4–4 ). Endoscopy showed no ulcer after nine sonications. The maximum esophageal temperature was ≤42°C for these nine sonications, suggesting that esophageal ulceration is likely to occur whenever the esophageal temperature reaches 50°C.
The ulcer was consistently located at the anterior wall of the esophagus, at the site of maximum left atrial pulsation, suggesting close proximity to the posterior left atrium. The size of the esophageal ulcer was directly related to the maximum luminal esophageal temperature ( Figure 4–5 ). Every esophageal ulcer was associated with transmural left atrial and esophageal necrosis on histologic examination. Nontransmural esophageal necrosis was not associated with ulceration on endoscopy or histology.
The distance between the ablation site and the esophagus was also important. For ultrasound ablation (HIFU and side-firing unfocused ultrasound), a high esophageal temperature (≥50°C) and esophageal ulcer occurred only when the ultrasound energy was applied within 2 mm of the esophagus when sonicating in the left atrium (outside the pulmonary vein). However, when sonicating inside the pulmonary vein, an esophageal ulcer occurred with energy delivered at distances of up to 6.8 mm from the esophagus. The reason that energy delivered within the left atrium more than 2 mm from the esophagus was not associated with esophageal ulceration is the high absorption of 9 MHz ultrasound energy by the atrial myocardium, reducing the amount of energy absorbed by the esophagus. When sonicating inside the pulmonary vein, a greater distance from the esophagus (≥7 mm) may be required to avoid esophageal injury. The lower absorption of ultrasound energy by the blood and thin pulmonary vein wall probably result in greater absorption (heat) by the esophagus.
The evolution of esophageal injury was followed for up to 4 weeks by serial endoscopy in 11 of the 20 dogs after HIFU or side-firing unfocused ultrasound ablation. All 11 dogs underwent sonication inside a pulmonary vein (HIFU in 5 dogs and side-firing unfocused ultrasound in 6 dogs), and all had an esophageal ulcer by endoscopy immediately after ablation. Endoscopy showed regression in the size of the esophageal ulcer at 1 to 2 weeks in 5 of the 11 dogs, with complete healing of the ulcer at 4 weeks. Gross and histologic examination at 4 weeks after ablation showed the healed ulcer with regeneration of the epithelium and segmental fibrosis of the mucosal and muscular layers. The esophageal lesion involved the periesophageal vagus nerves in only 1 of these 5 dogs.
The remaining six dogs (54%) had progression of the esophageal ulcer size on endoscopy at 1 to 2 weeks after ablation. In all six dogs, the increase in ulcer size was associated with esophagitis (pale appearance of the esophageal wall surrounding the ulcer; Figure 4–6 A ) and relaxation of the lower esophageal sphincter. Two of the six dogs had food in the esophagus, despite fasting for 20 hours before endoscopy (see Figure 4–6 A ). These findings suggest the presence of gastroesophageal reflux with reduced motility and lower esophageal sphincter tone. Endoscopy at 4 weeks showed decreasing ulcer size (healing) with reduction or resolution of esophagitis in four of the six dogs (see Figure 4–6 A ). Gross examination of the esophagus at 4 weeks in these four dogs showed incomplete healing of the ulcer ( Figure 4–6 B ). Histologic examination demonstrated segmental transmural fibrosis of the esophageal wall with incomplete regeneration of the epithelium (residual ulcer; see Figure 4–6 C ). The esophageal lesions involved the periesophageal vagus nerves (see Figure 4–6 D ) in all four dogs. The remaining two dogs experienced fever at 8 and 10 days, and died at 11 and 14 days, respectively, after the ablation. Postmortem examination demonstrated a marked increase in esophageal ulcer size (maximum diameter, 42 and 40 mm, respectively), and a fistula between the esophagus and the junction of left inferior pulmonary vein and left atrium ( Figure 4–7 ). Esophagitis extended between the ulcer and the stomach in both dogs (see Figure 4–7 A ). Importantly, the esophageal lesion involved large branches of the periesophageal vagus nerves in both dogs (see Figure 4–7 B ). These observations suggest that the progression of esophageal ulceration and the development of left atrial-esophageal fistula were related to esophagitis because of gastroesophageal reflux resulting from relaxation of the lower esophageal sphincter and reduced motility of the stomach. Relaxation of the lower esophageal sphincter and reduced gastric motility probably resulted from injury to the periesophageal vagal plexus at the time of ablation.
