Neurological Consequences of Atrioesophageal Fistula After Radiofrequency Ablation in Atrial Fibrillation

ORIGINAL CONTRIBUTION Neurological Consequences of Atrioesophageal Fistula After Radiofrequency Ablation in Atrial Fibrillation

Claudia Stöllberger, MD; Thomas Pulgram, MD; Josef Finsterer, MD, PhD

Background: Radiofrequency ablation for atrial fibril- 21 of 28 patients. Blood tests showed leukocytosis, el- lation (RAF) is an increasingly performed procedure. It evated serum C-reactive protein levels, and thrombocy- is performed during cardiac surgery or percutaneously topenia. Blood cultures were frequently positive for bac- by catheter. A dangerous complication of RAF is atrio- teria. Lumbar puncture revealed pleocytosis, elevated esophageal fistula (AEF), which predominantly mani- protein levels, increased lactate levels, and bacteria. Di- fests neurologically owing to food embolism. Because neu- agnosis was established by thoracic contrast computed rologists may not be familiar with AEF and the prognosis tomography. Endoscopy, insertion of nasogastric tubes, is dependent on a prompt diagnosis, awareness of AEF and transesophageal echocardiography were detrimen- by the neurologist may play a crucial role. tal, leading to an increase in fistula size and food or air embolism. Therapy comprised surgery (n=11) or tem- Objective: To summarize for the neurologist the knowl- porary esophageal stenting (n=1). The remaining pa- edge about fistula between the left atrium and esopha- tients died before attempted surgery or confirmation of gus occurring after RAF. the diagnosis. A neurological deficit persisted in 3 of the 9 surviving patients. Design, Setting, and Patients: Using a MEDLINE search, we collected reports about AEF after RAF in 28 patients. Conclusions: In patients with meningitis, stroke, seizures, or impaired consciousness and fever, it should be Main Outcome Measures: From the collected re- determined whether they have had a previous RAF. In ports, the description of symptoms, diagnostic investi- cases with a history of recent RAF, AEF should be strongly gations, therapy, and outcome of the 28 patients were considered, especially if there are also symptoms such summarized. as dysphagia or chest pain. After RAF, the patient, his or her family, and his or her treating physicians should be Results: In 28 cases, AEF developed 3 to 38 days after informed about the signs of AEF, which may occur even RAF. Confusion, grand mal seizures, meningitis, focal cor- weeks after RAF. tical signs, and postprandial transient ischemic attacks associated with fever were the leading manifestations in Arch Neurol. 2009;66(7):884-887

ADIOFREQUENCY ABLATION and the esophagus. The fistula may initially for atrial fibrillation (RAF) andpredominantlymanifestwithneurologi- is an increasingly per- cal abnormalities, and neurological abnor- formed procedure, applied malities are the main cause for hospitaliza- especially in patients with tion of patients with this complication paroxysmalR atrial fibrillation who are clas- (Table). Neurologists may not be familiar sified as refractory to antiarrhythmic drug withtheclinicalpresentationofthisrarecom- therapy. Radiofrequency ablation for atrial plication.However,theprognosisofpatients fibrillation is performed either during car- with a fistula is highly dependent on prompt diac surgery as an additional procedure or andappropriatediagnosisandtherapy.Thus, as a percutaneous catheter intervention. It awareness of atrioesophageal fistula (AEF) is associated with various complications by the neurologist may play a crucial role in Author Affiliations: Second such as pericardial effusion, pericardial tam- the survival of patients with this life- Medical Department ponade, pulmonary vein stenosis or throm- threatening disease. (Dr Stöllberger) and Fourth 1 Medical Department bosis, and left atrial wall hematoma. The aim of this review is to summa- (Dr Pulgram), Krankenanstalt Probably the most dangerous, life- rize for the neurologist the knowledge Rudolfstiftung (Dr Finsterer), threatening complication of RAF is the de- about fistulas occurring between the left Wien, Austria. velopmentofafistulabetweentheleftatrium atrium and esophagus after RAF.

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©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 Table. Patients With Atrioesophageal Fistula After Surgical or Interventional Therapy of Atrial Fibrillation

Age, y/ Time After Symptoms Source Sex Procedure Procedure, d and Findings Cerebral Imaging Therapy Outcome Preis et al,2 56/M PRFA 38 Fever, bilateral arm Multiple foci of Surgery Survived, expressive 2007 (n=1) weakness restricted aphasia diffusion Cummings et NR/M=4, PRFA 10-16 Sepsis, embolic strokes Intravascular air NR Died al,3 2006 F=5 (n=8), angina pectoris (n=2) (n=9) (n=2), gastrointestinal bleeding (n=3) Sonmez et al,4 58/F SRFA 22 Fever, numbness of right Ischemic lesions Surgery Died on 20th 2003 (n=1) arm postoperative day Schley et al,5 37/M PRFA 25 Fever, grand mal seizure, NR Surgery attempted Died during 2006 (n=1) status epilepticus preparation for surgery Scanavacca et 72/M PRFA 22 Dysphagia, fever, loss of NR Gastroesophageal Died al,6 2004 consciousness after endoscopy (n=1) eating, tonic-clonic seizures, hematemesis Pappone et al,7 36/M PRFA 3 Fever, pleuritic chest pain, Bilateral ischemia Surgery Survived, left 2004 (n=1) convulsions hemiparesis Pappone et al,7 59/M PRFA 21 Fever, grand mal seizure Cerebral emboli Antibiotics Died 2004 (n=1) Ouchikhe et al,8 58/M PRFA 21 Fever, confusion, meningitis Bilateral hyperdense Antibiotics Died 2008 (n=1) lesions (frontal, occipital, parietal, and temporal) Doll et al,9 2003 42/M SRFA 10 Fever, postprandial NR Surgery Survived (n=1) transient ischemic attack Doll et al,9 2003 62/F SRFA 6 Hematemesis NR Endoscopy Died (n=1) Doll et al,9 2003 59/M SRFA 12 Fever, neurological NR Surgery Survived (n=1) symptoms Doll et al,9 2003 36/M SRFA 11 Chest pain NR Surgery Survived (n=1) Dagres et al,10 Mean, 51 SRFA (n=4), 8-28 Fever (n=3), chest pain NR Surgery (n=3), Survived (n=3), 2006 (n=5) (range, PRFA (n=2), hemiparesis attempted surgery died (n=2) 35-76)/ (n=1) (n=3), grand mal seizure (n=2) M=4, (n=1), aphasia (n=1) F=1 Bunch et al,11 48/M PRFA 14 Fever, chest pain, dysphagia NR Temporary stenting Survived 2006 (n=1) Malamis et al,12 59/M PRFA 35 Fever, altered mental state, Negative for Surgery Died during surgery 2007 (n=1) multiple petechiae ischemic changes Borchert et al,13 59/M HIFU 10 Fever, chest pain, Multiple ischemic Surgery Died on fifth 2008 (n=1) ventricular fibrillation, lesions postoperative day generalized seizures

Abbreviations: HIFU, percutaneous high-intensity focused ultrasound ablation; NR, not reported; PRFA, percutaneous radiofrequency ablation; SRFA, surgical radiofrequency ablation.

METHODS Esophagoatrial fistula may be due to esophageal in- juries such as perforation with feeding tubes, esopha- Using a MEDLINE search, we collected reports about fistulas geal biopsies, esophageal surgery, erosion of an esoph- between the left atrium and esophagus. We noted this in gen- ageal diverticulum into the left atrium, and carcinoma.14-21 eral and especially as a complication after RAF. In the search, Rheumatic mitral valve disease with an enlarged left atrium we found 28 cases of AEF that developed after RAF. and esophageal compression in association with the in- take of potassium chloride tablets has been reported as RESULTS a further cause of EAF.22 Atrioesophageal fistula has been described as in- ETIOLOGY OF FISTULA BETWEEN ESOPHAGUS duced by trauma such as after a gunshot wound of the AND LEFT ATRIUM chest.23 Atrioesophageal fistula after RAF may develop owing to the proximity between the left atrium and Depending on the site of the primary lesion, esophago- esophagus.24 Myocardial injury during RAF may also affect atrial fistula (EAF) and AEF must be differentiated. the esophageal wall.25 Whether reflux esophagitis, which

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©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 has been reported to be associated with paroxysmal atrial tients who develop neurological signs, delays in the diag- fibrillation, favors the development of AEF has not yet nosis probably contribute to the high mortality.10 been investigated to our knowledge.26 To reduce radiofrequency-induced tissue damage, alternative ablation LABORATORY FINDINGS techniques have been developed. However, AEF has also been reported as a complication of ablation using high- Blood tests show leukocytosis, elevation of serum intensity focused ultrasound (Table).13 C-reactive protein levels, thrombocytopenia, and an elevated erythrocyte sedimentation rate. Blood cultures PATHOLOGIC CONSEQUENCES are frequently positive for bacteria. Lumbar puncture may OF THE FISTULA reveal pleocytosis, elevated protein levels, increased lactate levels, and bacteria.8 A fistula between the left atrium and esophagus may lead to severe bleeding and food emboli. One might expect DIAGNOSIS hemorrhage to be more common than food emboli because at rest, left atrial pressure exceeds esophageal pres- Chest radiography or computed tomography of the chest sure. The lower viscosity of blood as compared with the may be diagnostic if air is visualized within the cardiac cavi- viscosity of food would further increase the likelihood ties or in the mediastinum, or if intravenous contrast me- of gastrointestinal bleeding.21 However, gastrointestinal dium enters the esophagus from the left atrium.5 Further- bleeding is only rarely reported (Table) and severe bleed- more, a contrast esophagogram may show extravasation ing has not been reported in AEF. of water-soluble contrast material in communication with There is a high incidence of food emboli in AEF lead- a pulsating chamber.2,8 Unfortunately, not all of these signs ing to life-threatening and mostly fatal “meat and veg- may be present in each patient and different diagnostic in- etable” systemic emboli and septicemia.14 Esophago- vestigations have to be carried out in suspected cases. Ap- atrial fistula as a cause of embolic meningoencephalitis plication of a barium swallow study should be avoided be- was first described in 1970.27 Those patients who pre- cause barium entering the circulation has detrimental sent with more insidious symptoms likely possess the ana- consequences. Furthermore, endoscopy, insertion of na- tomical equivalent of a single-way valve, allowing esoph- sogastric tubes, and transesophageal echocardiography ageal contents to enter the heart while preventing blood should not be carried out as they may lead to an increase entry into the esophagus. Further cerebral manifesta- in fistula size as well as possible food or air embolism from tions of AEF and EAF comprise abscesses as well as ce- inflation of air during the procedure.4,6,7,10 rebral air and food embolism.15,17,20 DIFFERENTIAL DIAGNOSIS EPIDEMIOLOGY Endocarditis is frequently suspected in cases with signs The incidence of AEF after surgical RAF is reported to of infection and positive blood cultures after an invasive be 1%.9,10 The incidence of AEF after percutaneous RAF cardiac intervention.2 Indeed, infective endocarditis at the is unknown and has been estimated to be between 0.05% left atrial appendage entrance, most likely induced by en- and 0.2%.7,10 It is probably markedly underreported. docardial damage during RFA, has been described re- Among the 28 reported cases listed in the Table, the mor- cently as a further complication of RFA and thus ren- tality of patients with EAF was 68%. The mortality was ders the situation even more complicated.28 It seems 40% after surgical RAF and 80% after percutaneous RAF, reasonable to consider endocarditis as a differential di- and persisting neurological deficits are reported in 3 of agnosis and to perform transesophageal echocardiogra- the 9 surviving patients.2,7,10 phy only after AEF has been definitively excluded. Meningitis is a further differential diagnosis. In fact, NONNEUROLOGICAL MANIFESTATIONS meningitis and pathologic findings of cerebrospinal fluid have been reported as a manifestation of AEF.8 These find- The clinical presentation of AEF includes lethargy, gen- ings suggest that in patients with meningitis, the neu- eral weakness, fever, chest pain, dysphagia, melena, he- rologist must always ask for a history of RFA. If there is matemesis, and sepsis (Table). The interval between the a history of RFA, AEF should be strongly considered. ablation procedure and the clinical manifestation of AEF Embolic stroke due to recurrent atrial fibrillation may varies from 3 to 38 days. frequently be a differential diagnosis because atrial fibrillation after RAF may recur, and a fistula between the NEUROLOGICAL MANIFESTATIONS esophagus and left atrium may induce atrial fibrillation.1,19 Patients with AEF frequently present with tran- Neurological abnormalities occur frequently in AEF sient ischemic attacks or stroke. Atrioesophageal fistula (Table). They comprise confusion, grand mal seizures, should be strongly considered if the events are associ- meningitis, focal cortical signs, and postprandial transient ated with fever or occur after meals. ischemic attacks. These abnormalities are most frequently Epileptic seizures and confusion are frequent mani- associated with fever. They are unspecific and may not lead festations of AEF (Table) but may also occur simply be- the neurologist to consider a cardiac cause for the patient’s cause of fever due to other causes. Thus, in patients with symptoms, especially if there are no findings such as scars seizures and confusion associated with fever, it should from surgery indicating a recent invasive procedure. In pa- always be determined whether they have a history of RFA.

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Therapy of AEF comprises surgical resection of the ne- 1. Natale A, Raviele A, Arentz T, et al. Venice Chart international consensus docu- crotic parts of the esophagus and closure of the left ment on atrial fibrillation ablation. J Cardiovasc Electrophysiol. 2007;18(5): atrium.13 Atrial laceration may be treated with a bovine 560-580. 2. Preis O, Digumarthy SR, Wright CD, Shepard JA. Atrioesophageal fistula after pericardial patch, and the esophageal laceration may be catheter pulmonary venous ablation for atrial fibrillation: imaging features. J Tho- treated with a purse-string suture.7 rac Imaging. 2007;22(3):283-285. Stenting of the esophagus is an established proce- 3. Cummings JE, Schweikert RA, Saliba WI, et al. Brief communication: atrial- 29 esophageal fistulas after radiofrequency ablation. Ann Intern Med. 2006;144 dure for interventional closure of esophageal leakages. (8):572-574. It was reported to have been successful in a single pa- 4. Sonmez B, Demirsoy E, Yagan N, et al. A fatal complication due to radiofre- tient with AEF.11 However, the safety of this procedure quency ablation for atrial fibrillation: atrio-esophageal fistula. Ann Thorac Surg. 2003;76(1):281-283. has to be further evaluated because endoscopy with its 5. Schley P, Gülker H, Horlitz M. Atrio-oesophageal fistula following circumferen- inherent risk of air embolism is necessary for appropri- tial pulmonary vein ablation: verification of diagnosis with multislice computed ate positioning of the stent. Furthermore, with an esoph- tomography. Europace. 2006;8(3):189-190. 6. Scanavacca MI, D’A´vila A, Parga J, Sosa E. Left atrial-esophageal fistula follow- ageal stent, only 1 side of the fistula is closed while the ing radiofrequency catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol. left atrial side remains open. 2004;15(8):960-962. 7. Pappone C, Oral H, Santinelli V, et al. Atrio-esophageal fistula as a complication of percutaneous transcatheter ablation of atrial fibrillation. Circulation. 2004; PROGNOSIS 109(22):2724-2726. 8. Ouchikhe A, Maindivide J, Le Bivic JL, Roux L, Vincent JF. Atrio-oesophageal Atrioesophageal fistula as a complication of RAF has a fistula after radiofrequency ablation: predominant neurological symptoms [in French]. Ann Fr Anesth Reanim. 2008;27:499-501. high mortality. According to the published cases (Table), 9. Doll N, Borger MA, Fabricius A, et al. Esophageal perforation during left atrial patients with AEF after surgical RAF have a higher chance radiofrequency ablation: is the risk too high? J Thorac Cardiovasc Surg. 2003; of survival than patients with AEF after percutaneous RAF. 125(4):836-842. 10. Dagres N, Kottkamp H, Piorkowski C, et al. Rapid detection and successful treat- This difference may be owing to the higher awareness of ment of esophageal perforation after radiofrequency ablation of atrial fibrillation: a complication if the procedure has been performed sur- lessons from five cases. J Cardiovasc Electrophysiol. 2006;17(11):1213-1215. 11. Bunch TJ, Nelson J, Foley T, et al. Temporary esophageal stenting allows healing gically as opposed to percutaneously. of esophageal perforations following atrial fibrillation ablation procedures. J Car- diovasc Electrophysiol. 2006;17(4):435-439. 12. Malamis AP, Kirshenbaum KJ, Nadimpalli S. CT radiographic findings: atrio- COMMENT esophageal fistula after transcatheter percutaneous ablation of atrial fibrillation. J Thorac Imaging. 2007;22(2):188-191. In patients with meningitis, stroke, seizures, or impaired 13. Borchert B, Lawrenz T, Hansky B, Stellbrink C. Lethal atrioesophageal fistula after pulmonary vein isolation using high-intensity focused ultrasound (HIFU). 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J Neurol Sci. 1997;149(2):185-190. about the signs of the life-threatening complication of AEF, 22. Sumithran E, Lim KH, Chiam HL. Atrio-oesophageal fistula complicating mitral which may occur even weeks after RAF. valve disease. Br Med J. 1979;2(6204):1552-1553. 23. Bliznak J, Ramsey JD. Atrio-esophageal fistula secondary to gunshot wound of the chest. Mil Med. 1971;136(6):584-585. Accepted for Publication: February 12, 2009. 24. Sa´nchez-Quintana D, Cabrera JA, Climent V, Farre´ J, Mendonc¸a MC, Ho SY. Correspondence: Claudia Stöllberger, MD, Krankenans- Anatomic relations between the esophagus and left atrium and relevance for ab- talt Rudolfstiftung, Steingasse 31/18, 1030 Wien, Aus- lation of atrial fibrillation. Circulation. 2005;112(10):1400-1405. 25. Schmidt M, Nölker G, Marschang H, et al. Incidence of oesophageal wall injury tria ([email protected]). post-pulmonary vein antrum isolation for treatment of patients with atrial fibrillation. Author Contributions: Study concept and design: Stöll- Europace. 2008;10(2):205-209. berger and Finsterer. Acquisition of data: Stöllberger and 26. Weigl M, Gschwantler M, Gatterer E, Finsterer J, Stöllberger C. Reflux esophagitis in the pathogenesis of paroxysmal atrial fibrillation: results of a pilot study. Finsterer. Analysis and interpretation of data: Stöllberger South Med J. 2003;96(11):1128-1132. and Pulgram. Drafting of the manuscript: Stöllberger and 27. Hojgaard K, Raaschou-Nielsen T. Oesophago-cardiac fistula: a fistula between heart Finsterer. Critical revision of the manuscript for impor- and oesophagus as causative agent in the development of embolic meningo-encephalitis. Acta Pathol Microbiol Scand Suppl. 1970;212(suppl):114. tant intellectual content: Stöllberger and Pulgram. Statis- 28. Weis S, Piorkowski C, Arya A, Bollmann A. Septic vegetation at the left atrial ap- tical analysis: Stöllberger. Administrative, technical, and pendage entrance after pulmonary vein ablation for atrial fibrillation. Europace. material support: Stöllberger and Pulgram. Study super- 2008;10(2):215-217. 29. Radecke K, Lang H, Frilling A, Gerken G, Treichel U. Successful sealing of be- vision: Stöllberger and Finsterer. nign esophageal leaks after temporary placement of a self-expanding plastic stent Financial Disclosure: None reported. without fluoroscopic guidance. Z Gastroenterol. 2006;44(10):1031-1038.

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