Handbook of Clinical Neurology, Vol. 119 (3rd series) Neurologic Aspects of Systemic Disease Part I Jose Biller and Jose M. Ferro, Editors © 2014 Elsevier B.V. All rights reserved

Chapter 11

Neurologic complications of catheter ablation/ defibrillators/pacemakers SMIT C. VASAIWALA* AND DAVID J. WILBER Cardiovascular Institute, Loyola University Medical Center, Maywood, IL, USA

INTRODUCTION

CLINICAL HISTORY

Approaches to the management of patients with cardiac arrhythmias have significantly evolved over the last decade, with advancement in catheter ablation and device implantation techniques. As the techniques and tools evolve, so does our understanding of the possible complications from these procedures. The focus of this chapter is to discuss the neurologic complications involved with catheter ablation, pacemaker and defibrillation implantation, with the focus on timely diagnosis, and management strategies.

Neurologic insult during cardiac procedures may be related to hypotension, hypoxia, use of contrast agents, use of antithrombotic medications, or embolization of air, debris, or pieces of atherosclerotic plaque during cardiac procedures (Duffis et al., 2007). This may result in global brain ischemia resulting in coma or encephalopathy, localized brain ischemia resulting in visual loss or cognitive defects, intracranial hemorrhage, or acute ischemic stroke (Adams, 2010). Patients may also experience long-term neuropsychological sequelae including memory loss or impaired executive functioning. Brain imaging performed following procedures may also detect silent or subtle ischemic strokes (Duffis et al., 2007). What follows is a discussion of specific neurologic complications associated with ablation procedures. Thromboembolic complications associated with ablation of atrial fibrillation are well described and discussed separately.

HISTORY Over the last few decades, catheter ablation has become a widely utilized clinical tool in the management of patients with cardiac arrhythmia. Also, the use of implantable pacemakers and cardiac defibrillators has increased for treatment of certain arrhythmias and prevention of sudden cardiac death. As the prevalence of these procedures has increased, there has been an increased understanding of associated complications. Although these complications are uncommon (Fuchs et al., 2002), they may be related to significant neurologic morbidity and even death (Adams, 2010). The purpose of this chapter is to discuss the neurologic complications associated with procedures involving cardiac ablation and device implantation, and to discuss strategies geared toward prevention, detection, and treatment of the complications. The majority of the chapter is geared toward discussion of neurologic complications with ablation including thromboembolic events, cerebral air embolism, and phrenic nerve injury. Neurologic complications associated with pacemaker and defibrillator placement are discussed separately.

Thromboembolism associated with ablation of atrial fibrillation The demographic of patients referred for ablation of atrial fibrillation (AF) is becoming increasingly complex, as the percentage of patients undergoing ablation for persistent AF with associated risk factors such as diabetes, hypertension, structural heart disease, and older age has increased (Cha et al., 2009). Thus there is an increased urgency for minimizing the risk of thromboembolic complications associated with AF ablation. Most studies have reported a 0.5% to 2.0% risk of stroke and transient ischemic episodes following radiofrequency ablation of AF (Chen et al., 1999; Zhou et al., 1999; Haissaguerre et al., 2000; Kok et al., 2002; Marrouche

*Correspondence to: Smit C. Vasaiwala, M.D., Loyola University Medical Center, 2160 South 1st Avenue, Building 110, Room 6232, Maywood, IL 60153, USA. Tel: þ1-708-216-9449, Fax: þ1-708-327-2377, E-mail: [email protected]

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et al., 2002; Oral et al., 2002, 2004; Pappone et al., 2003; Cauchemez et al., 2004; Ren et al., 2004; Cappato et al., 2005). This risk is generally reported to be higher in the earlier studies prior to maintenance of higher activated clotting time (ACT) in the more recent experience. The risk of fatal cerebrovascular accident is low, and occurs in about 1/10 000 cases (Cappato et al., 2009). The risk of thromboembolic complications associated with AF ablation is variable and influenced by the presence of various comorbid conditions. Oral et al. (2006) evaluated the risk of thromboembolism following percutaneous radiofrequency ablation of AF in 755 patients who underwent 929 AF ablation procedures. Thromboembolism occurred in 7/755 (0.9%) within 30 days of the ablation procedure. The authors concluded that the risk of postablation thromboembolism was 1.2%, with the highest risk being in the initial 1–2 weeks when the INR is still subtherapeutic. The risk of late thromboembolism was low (0.3%), with events occurring despite maintenance of therapeutic INR. The results indicated that ablation of AF was associated with early postprocedure thromboembolic events regardless of the presence or absence of sinus rhythm or risk factors for thromboembolism. The likely cause was char and/or thrombus formation at the sites of left endocardial ablation. One patient suffered a thromboembolic event in the setting of therapeutic anticoagulation, suggesting an inherent thromboembolic risk from the ablation procedure independent of anticoagulation status. The authors added that all patients underwent ablation with a nonirrigated-tip catheter that may be more prone to thrombus formation; this risk may be minimized with ablation performed with an irrigated-tip catheter. In a similar study, Bertaglia and colleagues (2007) collected clinical and procedural data from 1011 consecutive patients undergoing ablation for AF. In this study, 905 cases (89.5%) were performed with an open irrigated-tip catheter. They reported cerebral embolism in five (0.4%) patients (four major strokes, one transient

ischemic attack; four procedures performed with irrigated-tip catheter). Four events occurred on the day following the procedure while transitioning from intravenous unfractionated heparin to oral warfarin and one event occurred during the procedure. A single patient also experienced phrenic nerve paralysis during isolation of the right pulmonary veins. Due to a low number of events there were no clinical variables that significantly identified the patients that suffered the embolic events. The authors concluded that the lower embolic rates they observed in their study might have been a result of more aggressive procedural and periprocedural anticoagulation regimen and the use of irrigated-tip catheter. Other studies have tried to identify predictors of thromboembolic complications. In a study by Kok et al. (2002), 56 patients underwent catheter ablation for AF. Cerebrovascular accident occurred in three patients. All patients were more than 60 years old; however, age was not a statistically significant predictor in this study. Two out of three patients had history of previous transient ischemic attacks that proved to be a statistically significant clinical predictor for predicting thromboembolic risk in the setting of catheter ablation for AF. Silent infarction in the setting of atrial fibrillation is not uncommon. In the European Atrial Fibrillation Trial (EAFT Study Group, 1996), 14% of 985 patients had evidence of cerebral infarction on commuted tomography. Schrickel and colleagues (2010) investigated the incidence and predictors of silent cerebral embolism in 53 consecutive patients with low risk for thromboembolism undergoing catheter ablation for AF. All patients underwent a postprocedural cerebral diffusion-weighted MRI (DW-MRI) 1 day following the ablation procedure. In six patients (11%), DW-MRI depicted new clinically silent microembolism (Fig. 11.1). The study showed a high incidence of clinically asymptomatic cerebral microembolism following ablation. Patients with

Fig. 11.1. Two white matter lesions (arrows) seen on diffusion weighted image (DWI) (A) and apparent diffusion coefficient (ADC) map (B) consistent with acute embolic cerebral infarctions. Patient had no clinical sequelae. Fluid attenuated inversion recovery (FLAIR) (C) with extensive white matter lesion due to microangiopathy. (Reproduced from Schrickel et al., 2010, with permission.)

NEUROLOGIC COMPLICATIONS OF CATHETER ABLATION/DEFIBRILLATORS/PACEMAKERS 153 cerebral microembolism were more likely to have evidence of coronary artery disease, larger left ventricular volume and septal thickness, and were more likely to have failed treatment with multiple antiarrhythmic agents prior to ablation. The amount of radiofrequency energy applied was equal in both groups, substantiating the fact that further protective measures (i.e. standardization of the use of irrigated-tip catheters, activated clotting time screening, high flush sheaths, minimizing procedure times and manipulation in the left atrium) are important in preventing the possible devastating complication of cerebral embolism (Cauchemez et al., 2004; Schrickel et al., 2010). Scherr and colleagues (2009) reported their findings on 721 cases involving catheter ablation for AF. Despite implementation of commonly used procedures to minimize risk of thromboembolism, such as preprocedural transesophageal echocardiography, preprocedural anticoagulation, intraprocedural use of heparin, continuous flushing of transseptal sheaths, and use of irrigated-tip catheters, 10/721 patients (1.4%) suffered from periprocedural thromboembolic complications. In two separate multivariable analyses, having at least two risk factors for thromboembolism in the setting of AF (hypertension, age > 75, diabetes, or congestive heart failure) and history of cerebrovascular accident were found to be independent predictors of periprocedural cerebrovascular thromboembolism. The risk of thromboembolism was low (0.3%) in patients with no risk factors for thromboembolism. In the most recent study, Di Biase et al. (2010) investigated the role of periprocedural therapeutic international normalized ratio (INR) on the role of periprocedural stroke. This was a multicenter prospective study that categorized patients into three groups: those undergoing ablation with an 8 mm tip catheter without periprocedural warfarin (group 1), those undergoing ablation with an open-irrigated-tip catheter without periprocedural warfarin (group 2), and those with open-irrigated-tip catheters on warfarin (group 3). Periprocedural stroke/transient ischemic attacks occurred in 27 patients (1.1%) in group 1, and 12 patients (0.9%) in group 2. Despite greater risk factors for stroke and greater prevalence of nonparoxysmal AF, patients in group 3 incurred no strokes/transient ischemic attacks. Performing ablation with a therapeutic INR with an irrigated-tip catheter may be a potential strategy for stroke prevention in the setting of catheter ablation for AF. The risk of thromboembolism may be significantly reduced with the use of irrigated-tip catheters. In the recently reported Thermacool Study (Wilber et al., 2010), none of the 106 patients that underwent catheter ablation with irrigated-tip catheter incurred thromboembolic events.

Thromboembolism associated with catheter ablation of other supraventricular and ventricular arrhythmias The risk of thromboembolic complications during ablation of various supraventricular and ventricular arrhythmias has been reported to be between 0% and 1.3% (Hindricks, 1993; Greene et al., 1994; Kugler et al., 1994; Thakur et al., 1994; Chen et al., 1996; Epstein et al., 1996). In the study by Hindricks (1993), thromboembolic events occurred in 33/4398 (0.8% overall incidence) patients, including cerebral embolism in 0.4%. Procedure related thromboembolic complications in relation to the type of ablation varied from 0.2% for atrioventricular nodal ablation to 2.8% for ventricular tachycardia ablation (Scheinman and Huang, 2000; Delacretaz and Stevenson, 2001). Possible explanation for a higher incidence of thromboembolic complications with ablation of ventricular tachycardia include longer procedure duration, more ablation, and possibility of pre-existing thrombus not previously identified on echocardiography. In the study by Thakur et al. (1994), 3/153 patients undergoing catheter ablation on the left side of the heart experienced stroke; 2/3 patients that experienced stroke presented 3 months following the ablation. Only one patient had a history of AF. Also, the total amount of ablation performed in the patients with stroke was less than the patients that did not experience stroke. The authors concluded that the embolic events occurred despite anticoagulant therapy, and were not predicted by the amount of endocardial damage due to ablation, and that embolic complications may occur at a remote time following the ablation procedure.

Cerebral air embolism complicating catheter ablation procedures Cerebral air embolism is a rare complication of catheter ablation procedures and is usually a result of introduction of air into the arterial system at the time of sheath placement or catheter exchange. It is critical to establish the diagnosis of cerebral air embolism early, as management strategies can significantly alter the clinical course. Information regarding the course and prognosis of cerebral air embolism is mostly derived from a few case series (Aikawa et al., 1995; Wijman et al., 1998; Heckmann et al., 2000; Akhtar et al., 2001; Hinkle et al., 2001; Inamasu et al., 2001; Yang and Yang, 2005). The initial presentation may be more severe than that seen secondary to a cerebrovascular event from a thrombus. Patients may present with confusion, agitation, aphasia, and hemiparesis. There may be initial resolution of neurologic symptoms which may be transient (Hinkle et al., 2001). This is thought to be due to initial infarction

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from arterial occlusion, followed later by a thromboinflammatory response in the injured endothelium. Neuroimaging with either computed tomography or magnetic resonance imaging is generally unremarkable and diagnosis is established by clinical suspicion. Another manner by which air may enter the arterial system is via an atrioesophageal fistula. This devastating complication of catheter ablation of AF is fortunately rare, although incidence as high as 1% has been reported in some series, with mortality rates approaching 50% (Gillinov et al., 2001; Doll et al., 2003; Sonmez et al., 2003; Scanavacca et al., 2004). The relative anatomy of the posterior left atrium lying adjacent to the esophagus and the typical sites of ablation lesion makes the esophagus susceptible to thermal injury. Patients typically present with symptoms 3–28 days following the ablation (Stollberger et al., 2009). Mortality arises from widespread esophagoatrial air and septic embolization to the coronary and cerebral circulation along with morbidity associated with embolization to other organ systems. Neurologic symptoms include confusion, meningitis, grand mal seizures, focal cortical signs, and postprandial transient ischemic attacks associated with fever. Neuroimaging is consistent with various different findings including intravascular air, ischemic lesions, and evidence of cerebral emboli. Application of barium swallow is contraindicated due to the risk of barium entering systemic circulation. Also, transesophageal echocardiography or insertion of nasogastric tubes must be avoided due to the risk of food or air embolism from inflation of air during the procedure. Diagnosis is established by thoracic contrast computed tomography, which may show air within the cardiac cavities or contrast entering the left atrium from the esophagus (Schley et al., 2006). The strategies for management of cerebral air embolus as a result of either venous sheath placement or exchange, or as a result of atrioesophageal fistula are discussed later in the chapter.

Phrenic nerve injury during catheter ablation The right phrenic nerve courses anterior to the right superior pulmonary vein and posterior to the superior vena cava and courses down adjacent to the free wall of the right atrium (Bunch et al., 2005). This places it at risk of injury during radiofrequency ablation for AF (during isolation of right superior pulmonary vein) and atrial tachycardias originating from free wall of the right atrium (Durante-Mangoni et al., 2003). The left phrenic nerve can also be compromised with ablation for Wolf– Parkinson–White syndrome in the left atrium (Rumbak et al., 1996). The potential damage to the nerve is thought to be due to direct thermal energy with secondary

inflammation and edema (Haines and Watson, 1989). Clinical manifestations can range broadly from asymptomatic to severe respiratory dysfunction requiring prolonged mechanical ventilation, and mortality; however, most patients tend to be either asymptomatic or present with dyspnea. Complete or partial recovery occurs in most patients (Sacher et al., 2006). Phrenic nerve injury can be prevented by pacing at a high output to assess phrenic nerve capture in areas at risk for phrenic nerve damage prior to ablation. Ablation should be avoided in areas where there is phrenic nerve capture. Another approach involves placement of an epicardial balloon catheter to move the phrenic nerve away from the epicardial surface prior to ablation in an area where potential for damaging the phrenic nerve is high (Lee et al., 2009).

NATURAL HISTORY Thromboembolism during catheter ablation The natural history after thromboembolic event following catheter ablation is variable. In the Kok et al. study (2002), 3/56 patients had a cerebrovascular event. The first patient presented with right hemiparesthesia, followed with left hemiparesis and dysarthria. This patient had completely recovered at 18 month follow-up. The second patient developed dysarthria, hemiparesis, and diplopia, along with hemorrhagic infarct in the left cerebellum requiring emergent evacuation of clot for posterior fossa syndrome. This patient ultimately developed normal pressure hydrocephalus and required treatment with a ventriculoperitoneal shunt. At 1 year follow-up, the patient continued to require assistance with activities of daily living and a walking frame to ambulate. The third patient presented with left sided hemiparesis. At 14 month followup, she had regained full neurologic function. In the study by Oral et al. (2006), three out of nine patients had residual symptoms at 2 year follow-up. Scherr et al. (2009) reported periprocedural cerebrovascular accident in 10/ 721 (1.4%) cases undergoing catheter ablation of AF. The symptoms ranged from right or left hemiparesis (three patients and one patient, respectively), aphasia (two patients), visual field change (three patients), and left leg weakness. In three patients, neurologic symptoms resolved completely within 24 hours. In two patients, the symptoms resolved in the following weeks. In the remaining five patients, mild-moderate neurologic deficits persisted beyond 30 days.

Cerebral air embolism Cerebral air embolism is a rare complication of catheter ablation procedure. The majority of information regarding the natural history of cerebral air embolism in the setting of catheter ablation procedures comes from case

NEUROLOGIC COMPLICATIONS OF CATHETER ABLATION/DEFIBRILLATORS/PACEMAKERS 155 reports. Hinkle et al. (2001) describe two patients who suffered severe neurologic illness as a result of cerebral air embolism while undergoing catheter ablation for AF. The first patient suffered from a left homonymous hemianopsia with left facial droop, hemiparesis, and hemineglect. One month later, the patient exhibited only mild residual left arm weakness. The second patient suffered from global aphasia and right side hemiparesis. All neurologic deficits improved over 4 days and the patient was discharged with only mild residual language impairment, which also improved to baseline over the next several weeks. In another patient undergoing catheter ablation for AF, at the time of sheath exchange fluoroscopic contrast changes consistent with intracardiac air were observed (Mofrad et al., 2006). The patient subsequently went on to develop inferior ST-segment elevation on ECG associated with bradycardia and hypotension. He also developed a left hemiparesis. The patient was placed in a hyperbaric chamber, following which he regained control of both left sided extremities and ultimately gained fine motor control. At 4 days following ablation, the patient had attained full neurologic recovery. If cerebral air embolism is recognized and promptly treated, the outcomes can be favorable. Although the formation of atrioesophageal fistula complicating atrial fibrillation ablation is rare, the consequences are usually devastating (Sonmez et al., 2003; Pappone et al., 2004; Schley et al., 2006; Malamis et al., 2007). In the five patients presented in the above case series, only one patient survived. To have any chance at survival the diagnosis needs to be made promptly, with immediate surgical repair following the diagnosis. Even with early diagnosis and treatment, the mortality following atrioesophageal fistula remains high.

LABORATORY INVESTIGATIONS Catheter ablation of atrial fibrillation There are no specific laboratory tests that are routinely recommended to aid in prevention, evaluation, or treatment of neurologic complications associated with catheter ablation of AF. There may be increased thrombogenicity with insertion and presence of catheters in the heart as measured by levels of thrombin-antithrombin III, D-dimer and prothrombin fragment 1 þ 2 with and without application of radiofrequency ablation lesions (Manolis et al., 1996; Michelucci et al., 1999; Lee et al., 2001) A greater degree of D-dimer level elevation may be seen in patients that had ablation, indicating a greater degree of thrombus production as compared to those patients undergoing only electrophysiology studies. Although this finding has not been consistently validated by all studies (Dorbala et al., 1998), it does provide a stimulus for

exploring the utilization of intravascular catheters coated with heparin.

Cerebral air embolism Laboratory evaluation in the setting of cerebral air embolism as a result of atrioesophageal fistula is likely to reveal leukocytosis, elevation of markers of inflammation such as C-reactive protein and erythrocyte sedimentation rate, and thrombocytopenia. Blood cultures are frequently positive for bacteria (Stollberger et al., 2009).

NEUROIMAGING INVESTIGATIONS Thromboembolism during catheter ablation When assessing an acute stroke both the location of neurologic insult and potential for recovery need to be assessed. Often a noncontrast head coronary tomography (CT) is usually utilized as the initial imaging modality since it allows for rapid acquisition and provides information regarding the location and extent of ischemia. CT or magnetic resonance perfusion imaging allow for assessment of not only the location, but also the extent of cerebral blood flow and volume (Shetty and Lev, 2005; Lickfett et al., 2006). This in turn allows for accurate assessment of the extent of ischemic territory, vascular reserve, and reversibility. Transcranial Doppler (TCD) monitoring has been utilized for monitoring microemboli during ablation (Sauren et al., 2009). Increasing numbers of microembolic signals (MES) have been detected with increasing power, duration, and temperature of ablation, and with the use of radiofrequency ablation as compared to cryoablation. Since there is a correlation between cerebral microemboli and brain damage (Kilicaslan et al., 2006; Lickfett et al., 2006), lower incidence of cerebral complications may be expected with reducing duration of each ablation, using irrigated-tip catheters, and using cryoablation rather than radiofrequency (Khairy et al., 2003; Sauren et al., 2009).

GENETICS Genetic polymorphisms that increase propensity to systemic hypercoagulability and thrombosis, such as prothrombin gene mutation, factor V Leiden, and protein C and S mutations, are well characterized (Monsuez et al., 2003). Although there are no specific genes implicated in increasing the propensity to thrombus formation with catheter ablation, it is likely that there are genetic differences between individuals, such as the ones described for systemic hypercoagulable states, that determine how much thrombus is generated and how readily it is dissolved by the endogenous fibrinolytic system (Zhou et al., 1999).

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PATHOLOGY

Cerebral air embolus

Endothelial cells are highly sensitive to injury, to the degree that even selective ablation with radiofrequency energy results in damage or loss of endothelium. The lining of the atrial and ventricular endocardium mediates natural anticoagulant properties by release of nitric oxide, prostacyclin, tissue plasminogen activator, and thrombomodulin. These mediators aid in clearance of newly formed fibrin and prevent thrombus formation. With the disruption of the endocardium with radiofrequency ablation, these properties are affected (Bombeli et al., 1997; Zhou et al., 1999), leading to a propensity toward thrombus formation. The gross examination reveals charring and endocardial disruption. The histology reveals endocardial disruption with loss of subendocardial architecture (Kongsgaard et al., 1994; Tanno et al., 1994). A better understanding of the pathophysiology of scar formation from catheter ablation should lead to improved methods of energy delivery to the endocardial and epicardial surface.

Recognition of cerebral air embolus is crucial as appropriate treatment can have favorable results. Following recognition of this complication, the most important initial step is to maximize cerebral perfusion. This is done with administration of intravenous fluids, supplemental oxygen, and placement of patient in a supine position with the head of the bed flat. Trendelenberg positioning is contraindicated as it may exacerbate cerebral edema. It is important to rule out intracerebral hemorrhage following these initial steps. Once that is ruled out, the patient is placed in a hyperbaric oxygen chamber, which is pressurized according to the US Navy Treatment Table 6 protocol (Mofrad et al., 2006). To our knowledge, there are five cases of cerebral air embolism reported in the literature that were treated with hyperbaric oxygen therapy (Hinkle et al., 2001; Mofrad et al., 2006). Although this is considered the treatment of choice for suspected air embolus by most, some have questioned its role in this setting (Heckmann et al., 2000). It is thought to promote absorption of nitrogen from the air bubble into the blood and to reduce endothelial injury from air embolism, potentially improving neurologic outcome (Muth and Shank, 2000). An absolute contraindication to hyperbaric oxygen therapy is untreated pneumothorax. Relative contraindications include upper respiratory infections, high fevers, seizure disorders, emphysema with carbon dioxide retention, uncontrolled hypertension, asthma, hypoglycemia, and pregnancy. Recent treatment with doxorubicin, disulfiram, cisplatinum, and mafenide acetate are also relative contraindications to hyperbaric oxygen. A directory of hyperbaric centers in the US is available on the website of the Undersea and Hyperbaric Medical Society (Weaver, 2010). It is imperative that clinicians involved in management of patients undergoing such catheter ablation procedures know about hyperbaric centers in the area of their practice. Lidocaine therapy may also play a role in managing cerebral air embolism. It has been shown to have protective effects from ischemia and to reduce intracranial pressure in animal studies (Mofrad et al., 2006). Administration of lidocaine in a bolus dose of 1.5 mg/kg with maintenance infusion thereafter has been shown to be helpful in treating patients with significant cerebral artery air embolus burden (Muth and Shank, 2000). Despite early recognition and therapy, the mortality associated with atrioesophageal fistula is significantly high. Besides supportive treatment including intravenous fluids and supplemental oxygen, definitive treatment comprises surgical resection of parts of the esophagus and closure of the left atrium (Borchert et al., 2008). Bunch and colleagues report a case where a patient underwent esophageal stenting following an ablation-induced atrioesophageal fistula, with complete defect resolution 3 weeks following stenting (Bunch et al., 2006).

MANAGEMENT Thromboembolism during catheter ablation Early heparinization prior to transseptal puncture (Bruce et al., 2008), higher intensity of anticoagulation with heparin and intracardiac echocardiographic imaging during the procedure (Ren et al., 2005; Wazni et al., 2005), the use of high-flow perfusion sheaths (Cauchemez et al., 2004), and ablation of patients with therapeutic INR may minimize the risk of thromboembolic complications. Although the risk may be low, the cost to the patient is enormous, making very early recognition and management of this complication imperative. There are minimal published data on the management of embolic complications in the setting of catheter ablation. Most cerebrovascular events likely have to do with placement of intravascular catheters in the left atrium or coagulum formation as a result of tissue heating. The management of this complication requires a multidisciplinary approach with close collaboration with the electrophysiologist and the neurologist or neurointerventionalist. The choice of perfusion therapy depends on the length of symptoms prior to presentation with stroke, NIH Stroke Scale, and coronary tomography perfusion data showing salvageable ischemic tissue (Ghanbari et al., 2009). Intravenous thrombolysis with recombinant tissue plasminogen activator (tPA) is currently FDA-approved for treatment of acute stroke with symptoms of less than 3 hours duration. Other techniques such as intra-arterial tPA or mechanical embolectomy may also be considered (Furlan et al., 1999; Smith et al., 2008).

NEUROLOGIC COMPLICATIONS OF CATHETER ABLATION/DEFIBRILLATORS/PACEMAKERS 157 echocardiography or monitoring with continuous tranNEUROLOGIC COMPLICATIONS scranial Doppler may have a role in ablation procedures ASSOCIATED WITH PACEMAKERS AND (Zhou et al., 1999). Biochemical measures of thrombin DEFIBRILLATORS activity such as thrombin-antithrombin complex, platelet Neurologic complications associated with placement of activity such as P-selectin, and fibrin formationpacemakers and defibrillators are rare. Most of the degradation such as D-dimer may also serve as surrogate knowledge regarding these complications comes from measures of thromboembolism in patients undergoing case reports. One of the well-recognized complications catheter ablation. with device implantation is capture of the phrenic nerve At this time there is no specific evidence for prevenand diaphragmatic stimulation. Although this complition of thromboembolism with anticoagulant therapies. cation can be avoided with high output pacing to The role for newer anticoagulants targeting indirect or assess phrenic capture at the time of implantation, it direct thrombin inhibition and newer antiplatelet agents is difficult to exclude phrenic nerve capture that may to prevent thromboembolism in the setting of catheter result from changes in body position once the patient ablation needs further study. In the meantime, unfractiobecomes ambulatory. Management of this complicanated heparin, low molecular weight heparin, and warfation requires repositioning of the lead (Hamid et al., rin remain the standard anticoagulant agents for patients 2008). undergoing catheter ablation. Since the implantation of these devices requires Alternate sources of energy to radiofrequency, such placement of venous sheaths, there is a potential for as cryothermal energy, microwave, and laser, are availair embolism; however, cerebral air embolism would able. Of these, cryothermal energy is widely accepted in theory require a right to left shunt across the cardiac and utilized for ablation of several different arrhythchambers. To the best of our knowledge, there have mias, including atrial fibrillation (Chierchia et al., been no case reports of cerebral air embolism during 2009). Cryothermy has the advantage of leaving the placement of pacemakers or defibrillators. endothelium intact, and has been shown to have a Pacemaker lead thrombus and vegetation have been reduced risk of stroke in patients undergoing ablation reported to cause thromboembolic events in patients for Wolf–Parkinson–White syndrome (Gallagher with patent foramen ovale (PFO). Transesophageal echoet al., 1977). Definitive data on whether this advantage cardiography may be able to visualize the presence of is present with ablation of AF is lacking and there are thrombus or vegetation. Lead thrombus may be an some reports that suggest significant risk for phrenic unrecognized source of thrombus in patients with crypnerve damage with this technology (Saliba et al., togenic stroke. In patients presenting with neurologic 2002). This risk was also seen in the Sustained Treatsequelae who are found to have a PFO and lead thromment of Paroxysmal-AF trial that was recently prebus, closure of PFO may be considered (Michaels and sented at the American College of Cardiology 2010 Burlew, 2009). meeting, where 29/245 patients undergoing catheter ablation had phrenic nerve injury (O’Riordan, 2010). Laser and microwave energy do lead to endothelial disCONCLUSION ruption, like radiofrequency ablation. It remains Cerebral embolism is an infrequent complication associunclear whether shorter procedure times associated ated with catheter ablation procedures and rare with with these technologies will lead to fewer thromboemdevice implantation. Early recognition of this problem bolic complications. could have a significant impact in the overall prognosis. Percutaneous strategies to exclude left atrial appendClose collaboration with the neurologist or neurointerage from the circulation via either an endocardial or epiventionalist is important in guiding management of cardial approach seem promising; however, definitive these patients. The timing of the events could be acute data toward stroke prevention are lacking (Onalan and in the setting of the procedure or could be delayed Crystal, 2007; Singh et al., 2010). (Oral et al., 2006). Postprocedure thromboembolic comDespite appropriate measures, cerebral embolism plications can occur despite maintenance of sinus remains a potential complication of cardiac procedures rhythm or the presence of risk factors for involving catheter ablation and device implantation. thromboembolism, thereby stressing the need for Early recognition and treatment of these problems is aggressive anticoagulation in the early postprocedure imperative as it may have a significant impact on progperiod. nosis for the patient. With advent of newer imaging Neuroimaging techniques and laboratory evaluation modalities, ablation techniques and medical therafor recognition of cerebral thromboembolism in the pies, one may expect to see fewer neurologic comsetting of catheter ablation are evolving. Real time plications and improved survival following these imaging of thrombus formation with transesophageal complications.

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