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Minimising silent cerebral ischaemic lesions

Cerebral embolism during transcatheter atrial fibrillation ablation remains one of the most feared complications
Matteo Anselmino MD PhD
Mario Matta MD
Fiorenzo Gaita MD 
Division of Cardiology,
Department of Medical Sciences,
University of Turin, Italy
Transcatheter ablation of atrial fibrillation (AF) is a therapeutic option for patients remaining symptomatic despite optimal pharmacological treatment. Its aim is to relieve AF-related symptoms, restore sinus rhythm and prevent AF-related complications.(1) The procedural endpoint is elimination of the triggers responsible of AF instauration and the modification of the substrate underlying AF maintenance, usually achieved through pulmonary vein isolation and, when needed, additional left atrial lines.
As an invasive procedure, catheter ablation carries a risk of complications, the most feared being stroke and cardiac tamponade. In particular, cerebrovascular accidents remain the most frequent major complications, ranging from 0.4 to 1.0%(1) Many attempts have been made during the past years to reduce this incidence, but it has not, at present, been possible. 
Besides symptomatic embolic events, a relatively high incidence of silent cerebral ischaemic lesions has also been described. New silent cerebral ischaemias (SCI) can be detected following cerebral magnetic resonance imaging (MRI) before and after AF transcatheter ablation.(2) The link between SCI and clinical significance is under investigation and a preliminary study has reported that SCI related to higher levels of neurocognitive impairment and dementia compared with control patients in sinus rhythm.(3) Silent cerebral embolism during AF ablation should therefore not be ignored, because it might carry a similar potential risk.
Mechanisms of silent cerebral embolism
Three mechanisms are involved in SCI pathogenesis: clot formation; char formation; and air/gas embolism.(2) Clot formation may be a consequence of sheath and catheter introduction, because any foreign body introduced into the blood stimulates coagulation activation. Heparin administration is recommended during AF ablation to maintain an activated clotting time (ACT) between 300 and 400 seconds,(4) to limit both thrombotic and haemorrhagic complications. Char formation during AF ablation is related to the energy source used during the procedure. Radiofrequency (RF) energy is used most frequently, and produces thermal damage of atrial tissue responsible of electrical conduction block, leading to isolation of triggers and interruption of circuits underlying AF instauration and maintenance. 
However, this mechanism is also responsible of endothelial layer damage and coagulation cascade activation, which might lead to thrombus formation, despite a good level of anticoagulation.(5) This mechanism has been limited with the introduction of irrigated catheters, characterised by a continuous saline irrigation that allows effective heat dispersion, and avoiding tissue overheating. Alternative energy sources, such as cryoenergy, have been reported to induce lower platelet and fibrin activation during in vitro studies; however, results are contradictory.(2)
Gas embolism is the third mechanism. Gas microbubble formation has been demonstrated in experimental models: elevated temperatures at the tissue–electrode interface produce two patterns of microbubbles. Type 1, or scattered microbubbles, with a concentration <1μl per minute of ablation, reflect early tissue overheating; type 2, or continuous microbubbles, with a concentration >1μl per minute of ablation, reflect impedance rise during RF delivery.(6) Air embolism may also be related to the introduction of bulky devices, such as multielectrode, non-irrigated ablation catheters and balloons.
Current evidence 
Since this phenomenon was first detected, a number of studies have analysed the incidence of new SCI following AF transcatheter ablation (Table 1). The first studies reported an incidence of SCI following AF ablation between 10% and 38%.(2) It is noteworthy that a higher incidence was found among patients with an ACT <250 seconds and among those who underwent electrical cardioversion at the end of the procedure. 
Different protocols aimed at reducing the incidence of SCI have given encouraging results.(2) A lower incidence of SCI was produced by delaying cardioversion after one month of oral anticoagulation (OAC) with International Normalised Ratio 2–3 in patients with persistent AF at the end of the ablation procedure; similar results were seen after ablation under uninterrupted OAC plus heparin, maintaining ACT above 300 seconds, even if data are contradictory.(2) In fact, age, spontaneous echo contrast in the left atrium, complex fractionated atrial electrograms ablation and intraprocedural electrical cardioversion were described as SCI predictors, highlighting that clot formation is not the only mechanism responsible of post-ablation SCI.
Different energy sources and ablation tools may also affect the incidence of SCI.2 The pulmonary vein ablation catheter (PVAC) is a duty-cycle phased RF ablation catheter with the ability both to map and ablate, ensuring rapid and simple procedures.(7) The first results with this tool surprisingly reported a high incidence of SCI (approximately 38%). It is noteworthy that the strongest predictors of SCI were the contact of electrodes 1 and 10 and the simultaneous activation of four electrode pairs during energy delivery.(2) For this reason, a subsequent study has been performed with specific amendments, such as ensuring separation of electrodes 1 and 10, deactivating electrode pairs not maintaining good contact with the pulmonary veins during ablation, and reducing air entrance by a submerged introduction/exchange technique. The procedure was also performed on OAC and with a procedural ACT target of 350 seconds, with a very low incidence of SCI (approximately 1.7%).(8)
Cryoablation has also been investigated, with contradictory results in relation to SCI incidence, which has been reported between 6 and 41%(2) (although the highest incidences have been reported by 3-Tesla cerebral MRI scans). Eventually, other different ablation tools, such as a balloon-like catheter delivering RF and a laser-balloon have been investigated, reporting incidence of SCI respectively 27% and 13.6%.(2) Even among these patients age was a predictor of SCI.
In summary, the incidence of SCI following AF catheter ablation is a relatively frequent complication, even if predictors of SCI are not yet completely categorised. The heterogeneous results among different studies most probably reflect the variety of procedural AF ablation techniques, protocols, operators experience, patient selection and also cerebral MRI protocols.
Clinical significance 
At present, few studies are available concerning the impact of SCI on neurocognitive function; these report different results, from no neurological impairment to a reduction concerning verbal memory(2) or a subtle cognitive dysfunction.(9) Clinical findings might, in fact, be influenced by the evolution of SCI over time. Repeated cerebral MRI three months after the procedure has reported the disappearance of the majority (82–100%) of the previously detected post-ablation SCI, especially those with lower dimensions (<10mm2). 
This preliminary evidence suggests that SCI may disappear or at least reduce under the spatial resolution of cerebral MRI during the follow up. However, it is not clear if SCI disappearance relates to complete neuronal recovery, or if it might originate in long-term neurological and cognitive impairment. In fact, an animal model has shown that SCI found at cerebral MRI always result in anatomical findings in histological analysis.(10)  Considering the significant number of patients undergoing transcatheter ablation and requiring repeated procedures to achieve rhythm control, the potential impact of silent lesions cannot be ignored. 
Preventive measures
Although the available literature does not permit conclusive statements, some specific recommendations to minimise the risk of SCI can be made (Figure 1). Patient selection is relevant, age being one of the recurrent risk factors; clinical history of paroxysmal AF and brief arrhythmia duration are also related to a lower incidence of SCI compared with long duration of arrhythmia. A small left atrial volume is likely to be related to reduced incidence of SCI, while left ventricular ejection fraction, left ventricular hypertrophy and concomitant coronary artery disease need to be investigated further.
Considering procedural characteristics, in patients with persistent AF at the end of the procedure, electrical cardioversion should be delayed for at least one month following therapeutic OAC. In addition, optimising time to reduce total energy delivery and procedure duration may be useful to reduce the incidence of SCI. The limited number of catheters used, the minor number of exchanges, the most careful device insertion under the saline submerged technique and sheath management, together with long sheath withdrawal into the right atrium after trans-septal puncture, are likely related to reduce the incidence of SCI related to air embolism. Cerebral MRI needs also to be standardised to permit homogenous comparisons within patients, ablation tools and techniques.
In conclusion, post-ablation SCI are widely described as a frequent complication of AF catheter ablation. Their evolution over long-term follow-up and clinical impact are, however, less characterised and substantially unknown; additional data are therefore needed to comprehensively describe the precise genesis and clearly identify correctable predictors of SCI to improve AF transcatheter ablation safety. 
  1. Camm AJ et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation. Eur Heart J 2012;33(21):2719–47. 
  2. Anselmino M et al. Silent cerebral embolism during atrial fibrillation ablation: Pathophysiology, prevention and management. J Atrial Fib 2013;6(2):16–22.
  3. Gaita F et al. Prevalence of silent cerebral ischemia in paroxysmal and persistent atrial fibrillation and correlation with cognitive function. J Am Coll Cardiol 2013 Jun 29. doi: 10.1016/j.jacc.2013.05.074. 
  4. Calkins H et al. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation Heart Rhythm 2012;9(4):632–96.e21. 
  5. Wazni OM et al. Embolic events  and char formation during pulmonary vein isolation in patients with atrial fibrillation: impact of different anticoagulation regimens and importance of intracardiac echo imaging. J Cardiovasc Electrophysiol 2005;16(6):576–81.
  6. Wood MA et al. Microbubbles during radiofrequency catheter ablation: composition and formation. Heart Rhythm 2005;2(4):397–403. 
  7. Beukema RP et al. Efficacy of multi-electrode dutycycled radiofrequency ablation for pulmonary vein disconnection in patients with paroxysmal and persistent atrial fibrillation. Europace 2010;12:502–7.
  8. Verma A et al. Evaluation and reduction of asymptomatic cerebral embolism in ablation of atrial fibrillation, but high prevalence of chronic silent infarction: Results of the ERACE Trial. Circ Arrhythm Electrophysiol 2013 Aug 27. doi 10.1161/CIRCEP.113.000612.
  9. Medi C et al. Subtle post-procedural cognitive dysfunction after atrial fibrillation ablation. J Am Coll Cardiol 2013;62(6):531–9.
  10. Haines DE et al. Microembolism and catheter ablation II: effects of cerebral microemboli injection in a canine model. Circ Arrhythm Electrophysiol 2013;6:23–30.