Context.—

Esophageal fistula formation is one of the most feared complications of radiofrequency catheter ablation. This procedure and its many variations, such as the “maze,” are becoming the mainstream treatment for atrial fibrillation owing to limitations of antiarrhythmic drugs. The incidence of this complication rate has been reported to be from 0.01% to 1%.

Objective.—

To delineate the importance of using the en bloc Letulle method of dissection for identifying esophageal fistulas for cases with a history of radiofrequency catheter ablation.

Design.—

Six autopsy cases with a history of radiofrequency catheter ablation for atrial fibrillation were selected from 1736 autopsies performed between 2009 and 2020.

Results.—

The initial presenting symptoms included neurologic symptoms, chest pains, epigastric discomfort, and sepsis. Transesophageal echocardiogram in 4 cases showed no evidence of thrombus or vegetation, however, 2 cases had evidence of atrial esophageal fistula. The autopsy findings included 5 atrial esophageal fistulas and 1 esophagopericardial fistula. Atrial esophageal fistulas were small and could be detected without difficulty when the en bloc Letulle technique was used and would have been easily missed by the Virchow method. The immediate causes of the deaths were myocardial ischemia, septic emboli to brain and heart, hypovolemic shock secondary to exsanguination, stroke, and coagulopathy.

Conclusions.—

To date, this is the largest collection of autopsy cases showing esophageal fistula associated with prior radiofrequency catheter ablation. The Letulle dissection method is preferable in this setting.

Esophageal fistula (EF) is one of the most serious complications of the Cox Maze and left atrial pulmonary venous ablation procedure. As atrial fibrillation arises from ectopic foci, destruction of these foci can limit episodes of atrial arrhythmias. Using this principle, the cut-and-sew Maze procedure was developed by Dr J. Cox in 1987 in which multiple incisions are made in the left and right atria in a mazelike fashion.1,2  Once these incisions heal and form scar tissue, they block the ectopic foci or reentrant circuits. The development of alternative energy sources has enabled surgeons to create lines of ablation to replace the incisions of the original Cox Maze procedure. Evolution of epicardial ablation tools created the ability to access portions of the left atrium either through mini-thoracotomies or by using thoracoscopic tools, thus leading to development of the total thoracoscopic Maze procedure. In 1998, Haissaguerre et al3  recognized pulmonary vein foci as initiators of atrial fibrillation, which currently forms the cornerstone of most interventional treatments of atrial fibrillation. This led to the development of the left atrial pulmonary venous ablation procedure, where ablation of cardiac/vascular tissue is performed most commonly with radiofrequency energy to induce a transmural heat injury, which later scars to isolate the electrical propagation of impulses. Catheters are typically introduced into the right atrium from the femoral vein up the iliac vein and vena cava. Catheters are guided by fluoroscopy, intracardiac echocardiography, and with the assistance of various mapping systems that help locate the ectopic foci, identify the depolarization pattern, position the ablation catheter, and evaluate ablation results. The ablation of cardiac tissue is performed most commonly with radiofrequency (microwave) energy to induce a transmural heat injury (60°C–70°C at the catheter tip) that scars to isolate the electrical propagation of impulses.1  Nowadays, it has become the mainstream treatment for atrial fibrillation owing to limitations of antiarrhythmic drugs.2  However, these procedures are associated with complications, especially the development of EF. The incidence of this complication rate has been reported to be 0.01% to 1% with a high mortality rate (∼55%). At least 120 cases have been reported in the literature at the time of this report.4  Autopsy is the diagnostic tool that allows detection and confirmation of EF. There are several methods that can be used for organ evisceration. The Virchow method (organ removal one by one), Rokitansky technique (in situ dissection combined with en bloc removal), Ghon technique (en bloc removal), and en bloc Letulle technique are among the most commonly used methods.5,6  The advantage of the Virchow method is that organs can be studied in detail, but anatomic relations of organs are not preserved. The Rokitansky technique is preferred to limit the spread of infectious diseases like HIV infection and hepatitis B, among others. The disadvantage of the Ghon technique is that interrelationships between different organ systems are not preserved. In the en bloc Letulle method, cervical, thoracic, abdominal, and pelvic organs are removed “en masse” and subsequently dissected as an organ block. This technique is best for preservation of relationships between organs and organ systems.6 

This study was exempt from the regulatory requirements of the National Institutes of Health regarding studies on deceased human subjects, as determined by the Institutional Review Board of The Ohio State University Wexner Medical Center (OSUWMC), Columbus, Ohio. Consecutive autopsy cases between January 2009 and December 2020 with a history of radiofrequency catheter ablation for atrial fibrillation were identified from the autopsy pathology database at the OSUWMC. Clinical presentation of one of these cases has been previously reported,7  and some clinical data are used here for comparison.

There were 1736 complete adult autopsies performed at the OSUWMC between 2009 and 2020. Among those, we identified 6 cases (0.35%) in decedents with a history of atrial ablation and a fistula between the esophagus and atrium (5 cases) and esophagus and pericardial space (1 case).

Clinical Presentation

Demographic data for the 6 cases are shown in the Table. Three females and 3 males underwent either a thoracoscopic Maze procedure (4 cases) or left atrial pulmonary venous ablation (2 cases). Maze procedure included surgery with chest incisions, and a femoral vein catheter access was used for the left atrial pulmonary venous ablation procedure. All patients developed clinical symptoms that included altered mental status (2 patients), fever (3 patients), nausea, and chest pain or epigastric discomfort (4 patients). Three patients had positive blood cultures for microorganisms (streptococcal species). Patients died on average 34.2 ± 18.6 days (range, 20–69 days) after the surgical procedure. The findings of the imaging studies were suggestive of EF in 3 of 6 patients.

Summary of the Autopsy Findings

All 6 cases showed a fistula between the esophagus and other organs. The fistula connected a mid-portion of the esophagus with the posterior wall of the left atrium in 5 cases and with the left posteriolateral pericardial space in 1 case. All fistula tracts were small and were detected after using the en bloc Letulle technique during autopsy (Figure, A and B). Microscopically, fistula tracks were inflamed and were partially necrotic (Figure, C). The fistula tracts would be easily missed or damaged by other methods of evisceration, such as the Virchow method. The immediate causes of the deaths were multifocal myocardial ischemia (1 case), hypovolemic shock due to exsanguination (1 case), acute infarcts in the brain (3 cases), and an antemortem coagulopathy (1 case).

Postmortem neuropathologic examination also revealed significant findings in the brain. Thus, in 4 of 6 cases significant ischemic changes of embolic origin were found, consistent with the neurologic deficits presented during admissions. None of the 4 cases with neuropathology findings had documented history of neurologic deficit before the complication. Additionally, ischemic changes in the myocardium were present in 3 of 6 cases. The pathologic mechanism of these ischemic changes in the brain and heart may include direct embolization of air through the fistula, embolization of esophageal contents, and thromboembolization secondary to coagulopathy. Indeed, evidence of intravascular thrombi in small vessels was found in 3 of 5 cases. The embolic-driven mechanism is consistent with the findings from prior case reports.7,8 

Fistula formation after atrial ablation is a rare but fatal complication. We identified EF in 6 of 1736 autopsy cases that were performed at our institution, or 0.35%. Despite advances in medical imaging, autopsy remains an important tool in investigating causes of death, such as investigating potential EF formation. Several autopsy techniques are in use by pathologists, including the Virchow, Letulle, and Ghon methods. We believe that the Letulle method, which uses en bloc organ removal and visualization of organ relationship, is preferable to use in patients with a known history of atrial ablation in order to properly visualize the anatomic defect that is otherwise easily missed owing to their small sizes.9  The Virchow method is not recommended because of lower emphasis on organ relationship. The Ghon method is more applicable to restricted autopsy and in facilities with a limited staff. In addition to the right technique, special attention is needed to the several anatomic areas, including esophageal mucosa, the lining of the major vessels in the vicinity of the surgical site, and the atrial endothelium.

We recommend detailed examination of the esophageal mucosa after longitudinal opening in situ of the esophagus. Fistula, if present, is easily visualized by esophageal wall defect and inflammatory reaction surrounding it; this will help to differentiate it from an incidental wall cut during the autopsy. The common location of the fistulae is consistent with previous case reports, likely due to the close proximity of the esophagus to the posterior wall of the left atrium, corresponding to the atrial ablation sites.7,8 

The clinical symptoms demonstrated in all 6 cases are broad and include altered mental status, neurologic changes, hypotension, nausea, fever, dysphagia, chest pain, shortness of breath, and urinary incontinence. The earliest symptoms appear to be chest discomfort and dysphagia before progression into altered mental status, neurologic changes, fever, and hypotension. Similar presentations were found in reported cases that led to hospital admission.811  Many patients in the reported cases also developed positive blood culture for mixed bacterial species.811  In all cases, death occurred within 2 months after the procedure (mean, 34.2 ± 18.6 days). The rapidly developing nature of this complication requires a high level of clinical suspicion after patients undergo a Maze procedure given the array of medical and surgical interventions that can be offered.8  Computed tomography of the chest and abdomen appears to be sensitive and specific for detecting the complication after admission, based on our findings, and is consistent with previously reported cases. Of note, clinical suspicion for EF was only relevant in 3 of 6 cases; thus, if the autopsy was performed by using a technique other than the Letulle technique (such as Virchow), even though a mucosal defect would be visible in the esophagus, the fistula association with other organs could be difficult to re-create.

The main pathogenesis of EF appears to be due to a thermal injury from the radiofrequency ablation procedure, as reported in previous investigations.12  In a study by Yamasaki et al,13  a mechanism is proposed in which excessive transmural injury of the esophagus is associated with patients with normal body mass index, perhaps owing to closer anatomic relationship between the left atrium and the esophagus. This hypothesis is not strongly supported by our findings, since in our series the body mass index in 5 of 6 cases was above 25 kg/m2. Unfortunately, there are not enough reported cases to allow any association of the complication to be pinpointed.

In summary, to the best of our knowledge, this is the largest collection of autopsy cases to date to illustrate the clinical and pathologic features of EF formation resulting from radiofrequency ablation for atrial fibrillation. We recommend using the Letulle method in any autopsy performed on patients with history of atrial ablation, with careful examination of the heart, esophagus, and brain. It is important to emphasize that clinical history and imaging are vital before a pathologist performs this technique, with discussion with clinicians before performing the autopsy.

The authors wish to express gratitude to Courtney Zola, MD, Matthew Ball, MD, Rebecca Ziegler, MD, Barrie Miller, MD, and Alena Taylor, BMS, who helped with collecting information for these cases.

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Author notes

The authors have no relevant financial interest in the products or companies described in this article.