CLINICAL RESEARCH
Europace (2015) 17, 898–901 doi:10.1093/europace/euu321
Ablation for atrial fibrillation
Headache during cryoballoon ablation for atrial fibrillation Laurent Pison 1*, Pim Peeters 2, Yuri Blaauw 1, Kevin Vernooy 1, Narendra Kumar 1, Suzanne Philippens 1, Harry J. Crijns 1, Johan Vlaeyen 2, Jean Schoenen 3, and Carl Timmermans 1 1 Department of Cardiology, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands; 2Department of Psychology, KU Leuven, Leuven, Belgium; and 3Headache Research Unit, University Department of Neurology, CHR de la Citadelle, Lie`ge, Belgium
Received 23 July 2014; accepted after revision 1 November 2014
Aims
Headache has been reported to occur during cryoballoon ablation for atrial fibrillation (AF). No study has systematically analysed this phenomenon. ..................................................................................................................................................................................... Methods Twenty consecutive patients with symptomatic AF underwent cryoballoon ablation without sedation. Headache was and results evaluated before, during, and after the first cryoapplication in every pulmonary vein (PV) using a visual representation of a head for location of the headache, a numerical rating scale (NRS) for measuring pain intensity and the short-form McGill pain questionnaire (MPQ) for qualitative analysis of pain. The order in which the PVs were ablated was randomized. Sixteen (80%) patients perceived mainly frontal headache during cryoablation. The overall NRS scores were significantly higher during (5.1 + 1.7), compared with before (2.7 + 1.4), and after (3.5 + 2.2) a cryoapplication (P , 0.05). The NRS score was significantly higher during ablation of the first PV. The intensity of the perceived headache was not related to the temperature reached 150 s after initiation of a cryoapplication (P ¼ 0.81). Of the MPQ, three sensory adjectives and one affective adjective averaged between scores 1 and 2, representing mild-to-moderate severity of pain. ..................................................................................................................................................................................... Conclusion The majority of patients treated by balloon cryoablation experienced headache during a cryoapplication. There was no correlation between the temperature reached during a cryoballoon freeze and the intensity of the headache. Cryoballoon ablation of the first PV was significantly more painful than the remaining PVs.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Ablation † Atrial fibrillation † Headache † Cryoballoon
Introduction Pulmonary vein (PV) isolation, with the endpoint of complete electrical isolation, is the cornerstone in atrial fibrillation (AF) ablation.1 Radiofrequency (RF) is currently the most widespread energy source used to perform PV isolation. Pulmonary vein stenosis, atrio-oesophageal fistula, and left atrial flutter are some of the potential procedural complications that may occur using RF energy.2 – 4 Cryothermal energy is used to overcome several disadvantages of RF energy such as tissue disruption by excess heating and generation of inhomogeneous lesions.5 In a case–control study, cryoballoon ablation as an initial ablation technique for patients with paroxysmal AF resulted in less recurrences and a lower AF episode burden compared with RF energy.6 Point-by-point cryoablation is known to result in nearly no application-related pain.7 Several studies, however, reported headache during cryoballoon
ablation.8,9 The aetiology of this phenomenon is unknown. The purpose of this prospective study was to describe and quantify headache during cryoballoon ablation for AF.
Methods Study population Twenty consecutive patients with symptomatic AF (18 paroxysmal and 2 persistent) underwent cryoballoon ablation (Table 1).
Electrophysiological study Each patient gave informed consent. The study and data collection were performed according to a protocol approved by the Medical Ethical Committee of the Maastricht University Medical Centre. Via a femoral venous approach, a His bundle (St Jude Medical) and coronary sinus
* Corresponding author. Tel: +31 43 3877095; fax: +31 43 3875104, E-mail address: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
899
Headache during cryoballoon ablation
What’s new? † This is the first study to systematically analyse the occurrence of headache during cryoballoon ablation for atrial fibrillation. † The majority of patients treated by balloon cryoablation experience headache during a cryoapplication. † The precise aetiology of the headache occurring during cryoballoon ablation remains unclear.
catheter (Medtronic) were positioned in the heart. Via a double transseptal puncture under transoesophageal echocardiography guidance, a steerable 12F sheath (Flex Cath, Cryocath Technologies, Inc.) and a long 8F sheath (SL0, St Jude Medical) were advanced into the left atrium (LA). Thereafter, intravenous heparin was given as a 100 IU/kg bolus dose followed by a heparin infusion to keep an activated clotting time .300 s. During rapid ventricular pacing from the His bundle catheter, contrast was injected through the long sheath in the mid-portion of the LA to visualize all the ostia and major branches of the PVs. The PVs were mapped for the presence of potentials using a circular mapping catheter (Lasso, Biosense Webster) inserted in the LA through the long sheath. A cryoballoon (Arctic Front, Cryocath Technologies, Inc.) was introduced in the LA via the steerable sheath. In each PV, a single cryoballoon application of 5 min was given. The order in which the veins were ablated was randomized. During cryoablation of the right superior PV, diaphragmatic excursion was observed during continuous phrenic nerve stimulation using the His bundle catheter placed in the superior vena cava. Headache was evaluated before, 150 s after the start and after the first cryoapplication in each PV using a visual representation of a head for exact location of the headache, a numerical rating scale (NRS) for measuring pain intensity and the short-form McGill pain questionnaire (MPQ) for qualitative analysis of pain. Both measures are widely recognized as a valid and reliable instrument to quantify and characterize pain, with a Dutch language version available.10,11 The drawing of a head, the NRS, and the MPQ were shown to the patients using a commercially available, head-mounted display (I glassesTM , model PC3D Pro). The drawing of a head was subdivided in seven zones (Figure 1). In case of pain, the patient was requested to select the zone(s) where headache occurred. The NRS was numbered from 0 to 10; 0 represented no pain and 10 represented the maximum score for pain. All patients were instructed how to answer the questions of the MPQ before the start of the procedure. The questionnaire contains pain-descriptive words arranged in progressively increasing intensity and words describing the sensory, affective, and evaluative dimensions of pain. The list of words is scored accordingly to the method described by Melzack.10 After one application in every PV, we reassessed the presence of potentials and, where necessary, performed further cryoballoon applications until complete entrance block. If PV isolation could not be obtained after two cryoballoon applications, a conventional cryocatheter (Freezor Max, Cryocath Technologies, Inc.) was used. No sedation was administrated during the procedure.
veins were ablated, pain zone, and temperature of the cryoballoon were entered as independent, second-level, fixed variables. Separate analyses were conducted for the dependent variables: pain scores (NSR) and MPQ scores. A variance components matrix was chosen. A stepwise procedure was used where the model started out as an intercept-only model with one level, adding first a second level, then the fixed factors, and finally a random slope, provided that each next step made a significant contribution to the model. A step was considered a significant improvement based on a x2 significance test on the difference in 22 log likelihood (22LL) between the previous and new model.
Results Patient characteristics Apart from arterial hypertension, the patients had no structural heart disease. One patient underwent a previous cryoablation for typical atrial flutter. The clinical and echocardiographic characteristics of the patients are summarized in Table 1.
Procedural characteristics Each patient had four separate PVs and in all of those veins potentials were present prior to the first cryoballoon application. One patient was in AF at the start of the procedure. All PVs were successfully
Table 1 Clinical and echocardiographic characteristics Age (years)
59 + 11
Gender AF duration (months)
15 men 72 + 79
LA size (mm)
41 + 5
LVEF (%) AHT (n)
61 + 6 6
AAD/patient (n)
0.8 + 0.4
Persistent AF (n)
2
AAD, antiarrhythmic drugs; AF, atrial fibrillation; AHT, arterial hypertension; LA, left atrium; LVEF, left ventricular ejection fraction.
Statistical analysis Statistical analysis was performed using SPSS 16.0. Continuous variables are summarized with means and standard deviations. All the results were considered to be significant at P , 0.05. Multilevel regression analyses were conducted with participant as the first level of the analyses. The timing of the measurement (pre-/during/ post-ablation), the specific vein being ablated, the order in which the
Figure 1 Visual representation of a head, subdivided in seven zones.
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isolated with a mean of 6 + 2 (range 4– 11) complete cryoballoon applications per patient. In five patients (25%), a 23 mm cryoballoon was used. A conventional cryocatheter was used to ablate residual myocardial tissue in four right inferior PVs (range 1–7 applications). The mean temperature at 150 s after the start of a cryoballoon application was significantly lower in the right superior PV compared with the other PVs (P , 0.05). The mean duration of the procedure was 181 + 26 min and the mean fluoroscopy time was 58 + 19 min (Table 2). No complications occurred during the course of the study.
Analysis of headache variables Sixteen (80%) patients perceived headache during cryoablation. Headache scores ranged from 0 to 8. The headache was usually located on the forehead (zones 2, 3, 4, or 5) (Table 3). The analyses yielded a significant interaction effect between the timing of the measurement (before, during, or after cryoablation) and the order of the cryoablation (which PV was ablated first, second, third, or fourth) (P , 0.05). The overall NRS scores were significantly higher during (5.1 + 1.7), compared with before (2.7 + 1.4), and after (3.5 + 2.2) a cryoapplication (P , 0.05). This was also the case for the individual PVs. The NRS scores during ablation were significantly higher in the PV that was ablated first (5.7 + 1.6) compared with the other PVs, irrespective of which PV was ablated first (P , 0.05). The intensity of the perceived headache was not related to the temperature reached 150 s after the start of a cryoballoon freeze (P ¼ 0.81). One patient also reported chest pain during cryoablation. Of the MPQ, three sensory adjectives and one affective adjective averaged between scores 1 and 2, representing a mild-to-moderate severity of pain. The most common adjectives used by the patients to describe the head pain during the PV isolation were: aching (1.5 + 0.8), tender (1.4 + 0.8), tiring exhausting (1.2 + 0.9), and heavy (1.1 + 0.8). The other MPQ adjectives scored lower than one, representing no to mild severity of pain. The total MPQ sensory score was higher during (0.7 + 0.4) than pre-ablation (0.6 + 0.3), but the difference did not reach statistical significance (P ¼ 0.057).
Discussion Main findings The main finding of this study is that in the majority (80%) of patients with AF treated by balloon cryoablation, frontal headache occurred during a cryoapplication. There was no correlation between the temperature reached during a cryoballoon freeze and the intensity of the perceived headache. Cryoablation of the first PV, irrespective of its localization, was significantly more painful compared with cryoablation of the other three PVs. It has been shown that the use of cryothermal energy, as compared with RF energy, for ablation of the cavotricuspid isthmus, results in nearly no application-related pain.7 The use of a different catheter design adjusted to the ablation target, a conventional cryoablation catheter for ablation of the cavotricuspid isthmus vs. a cryoballoon for PV isolation, may contribute to the occurrence of pain during ablation. The occurrence of pain during PV isolation with the use of RF energy has been analysed in two studies.12,13 Radiofrequency energy application in the LA, however, results in chest pain and not headache. Chest pain occurred in up to 87.5% of the patients, although in both studies patients were maintained under moderate
Table 3 Headache variables before, during, and after a cryoapplication Pain localization (n)
9
Zone 1
9
Zone 2 Zone 3
42 47
Zone 4
32
Zone 5 Zone 6
13 7
Zone 7
10
Overall VAS score Before cryoapplication
2.7 + 1.4
During cryoapplication
5.1 + 1.7
After cryoapplication 3.5 + 2.2 VAS score before/during/after cryoapplication
Table 2 Cryoballoon ablation characteristics Number of cryoballoon applications/patient (n)
6+2
23/28 mm balloon
5/15
Mean temperature at 150 s after the start of an application (degrees celsius) LSPV LIPV RSPV RIPV Procedure duration (min) Fluoroscopy time (min)
244 + 7 245 + 7 250 + 7 240 + 10 181 + 26
First PV
1.0 + 1.4/5.7 + 1.6/3.2 + 1.4
Second PV Third PV
3.1 + 1.4/5.0 + 1.8/1.6 + 1.4 1.3 + 1.5/4.8 + 4.3/2.9 + 1.5
Fourth PV
1.0 + 1.5/4.3 + 1.6/2.9 + 1.5
VAS score before/during/after cryoapplication LSPV 3.0 + 1.0/5.7 + 1.6/2.6 + 1.6 LIPV
2.2 + 1.2/4.6 + 1.6/4.2 + 2.7
RSPV RIPV
3.2 + 0.8/4.3 + 1.0/2.2 + 1.3 3.1 + 1.8/5.6 + 2.0/4.3 + 1.9
Mean MPQ score (SD) before/during ablation MPQ sensory MPQ affective
0.56 (0.34)/0.73 (0.37) (P ¼ 0.057) 0.74 (0.76)/0.74 (0.70) (P ¼ 0.441)
58 + 19
LIPV, left inferior pulmonary vein; LSPV, left superior pulmonary vein; RIPV, right inferior pulmonary vein; RSPV, right superior pulmonary vein.
LIPV, left inferior pulmonary vein; LSPV, left superior pulmonary vein; MPQ, McGill pain questionnaire; PV, pulmonary vein; RIPV, right inferior pulmonary vein; RSPV, right superior pulmonary vein; VAS, visual analogue scale.
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Headache during cryoballoon ablation
(‘conscious’) sedation throughout the procedure. The maximum temperature attained during a RF energy application showed a positive correlation with chest pain. Ablation at the left superior and inferior PV (especially the posterior and inferior aspects) resulted in significantly more pain than the other segments of the LA. The aetiology of chest pain during a RF energy application in the LA is not completely elucidated. One potential explanation includes the proximity of the ablation lesions to the oesophagus, resulting in tissue heating or deformation of the oesophageal wall, or the vascular and nerve plexus lining the oesophagus. The other explanations include the anatomic position of vagal and sympathetic afferents localized to the posterior wall and venoatrial junctions of the LA. Given that there is a large range in the headache report among the patients in this study, it is likely that the experience of pain during cryoballoon ablation is also influenced by individual differences.14 For example, we previously showed that differences in the personal meaning attached to the pain (such as pain catastrophizing) predicted the affective dimension of the pain reported during atrial cardioversion, despite the administration of a strong opioid (intranasal butorphanol tartrate).15 In future studies with cryoballoon ablation, we recommend to include such a measurement as well. Reducing catastrophizing thinking about pain through cognitive –behavioural techniques is likely to reduce pain levels, and may even increase the effectiveness of concomitant analgesics, when deemed necessary. The precise aetiology of the headache occurring during cryoballoon ablation is not well understood and we can only speculate on the possible underlying mechanisms. Vagal nerve stimulation in the mediastinum with referred pain is a possible explanation, but the pain is usually referred to the ipsilateral ear and teeth.16 Hypothermiainduced cerebral vasospasm has been reported during hypothermic circulatory arrest in cardiac surgery and is a plausible mechanism for headache during cryoballoon ablation.17 Cardiac cephalgia is less likely as it typically occurs during exertion in the setting of cardiac ischaemia and with unilateral headache.18 When explaining patients the course of a cryoballoon procedure not using general anaesthesia, physicians may inform their patients that headache may occur during cryoablation and reassure them that it concerns a transient phenomenon. If required, analgesics may be administrated.
Study limitations This study included a limited number of patients. But, as our intent was to describe and quantify headache during cryoballoon ablation, we consider our findings both interesting and valid in meeting our objectives. This is an observational study and it is therefore not possible to elaborate on causality. In this study, no individual psychological patient characteristics were measured. Another limitation of the study is that it was not sham-controlled, as no placebo applications were performed. Given the psychological implications of the pain perception, the anxiety of the patients due to their awareness that an application is being performed could modify the intensity and characteristics of the pain at that precise moment. Only simulating the application procedure without delivering cryoenergy could separate this effect from the real effects of the cooling.
Conclusion In the majority of patients with AF treated by balloon cryoablation, frontal headache occurred during and immediately after an application. Cryoablation of the first PV was significantly more painful compared with cryoablation of the other PVs. The underlying mechanism of headache during cryoballoon ablation remains unclear: potential mechanisms include vagal nerve stimulation, or hypothermia-induced cerebral vasospasm. Conflict of interest: none declared.
References 1. Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA 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. Europace 2012;14:528 – 606. 2. Saad EB, Rossillo A, Saad CP, Martin DO, Bhargava M, Erciyes D et al. Pulmonary vein stenosis after radiofrequency ablation of atrial fibrillation: functional characterization, evolution, and influence of the ablation strategy. Circulation 2003;108:3102 –7. 3. Pappone C, Oral H, Santinelli V, Vicedomini G, Lang CC, Manguso F et al. Atrio-esophageal fistula as a complication of percutaneous transcatheter ablation of atrial fibrillation. Circulation 2004;109:2724 –6. 4. Gerstenfeld EP, Callans DJ, Dixit S, Russo AM, Nayak H, Lin D et al. Mechanisms of organized left atrial tachycardias occurring after pulmonary vein isolation. Circulation 2004;110:1351 – 7. 5. Rodriguez LM, Leunissen J, Hoekstra A, Korteling BJ, Smeets JL, Timmermans C et al. Transvenous cold mapping and cryoablation of the AV node in dogs: observations of chronic lesions and comparison to those obtained using radiofrequency ablation. J Cardiovasc Electrophysiol 1998;9:1055 –61. 6. Linhart M, Bellmann B, Mittmann-Braun E, Schrickel JW, Bitzen A, Andrie´ R et al. Comparison of cryoballoon and radiofrequency ablation of pulmonary veins in 40 patients with paroxysmal atrial fibrillation: a case –control study. J Cardiovasc Electrophysiol 2009;20:1343 –8. 7. Timmermans C, Ayers GM, Crijns HJ, Rodriguez LM. Randomized study comparing radiofrequency ablation with cryoablation for the treatment of atrial flutter with the emphasis on pain perception. Circulation 2003;107:1250 –2. 8. Kojodjojo P, Davies DW. How to perform antral pulmonary vein isolation using the cryoballoon. Heart Rhythm 2011;8:1452 –6. 9. Defaye P, Kane A, Chaib A, Jacon P. Efficacy and safety of pulmonary vein isolation by cryoablation for the treatment of paroxysmal and persistent atrial fibrillation. Europace 2011;13:789 –95. 10. Melzack R. The short-form McGill pain questionnaire. Pain 1987;30:191–7. 11. Verkes RJ, Vanderiet K, Vertommen H, Van der Kloot WA, Van der Mey J. De MPQ-DLV, een standaard Nederlandstalige versie van de McGill Pain Questionnaire voor Belgie¨ en Nederland. In van der Kloot WA, Vertommen H (eds). De MPQ-DLV, een standaard Nederlandstalige versie van de McGill Pain Questionnaire: achtergronden en handleiding. Lisse: Swets & Zeitlinger, 1989. pp. 57 –69. 12. Alaeddini J, Wood MA, Parvez B, Pathak V, Wong KA, Ellenbogen KA. Sit localization and characterization of pain during radiofrequency ablation of the pulmonary veins. Pacing Clin Electrophysiol 2007;30:1210 – 4. 13. Aryana A, Heist EK, D’Avila A, Holmvang G, Chevalier J, Ruskin JN et al. Pain and anatomical locations of radiofrequency ablation as predictors of esophageal temperature rise during pulmonary vein isolation. J Cardiovasc Electrophysiol 2008;19:32–8. 14. Arntz A, Claassens L. The meaning of pain influences its experienced intensity. Pain 2004;109:20 –5. 15. Vlaeyen JW, Timmermans C, Rodriguez LM, Crombez G, van Horne W, Ayers GM et al. Catastrophic thinking about pain increases discomfort during internal atrial cardioversion. J Psychosom Res 2004;56:139 –44. 16. Schoenen J, Broux R, Moonen G. Unilateral facial pain as the first symptom of lung cancer: are there diagnostic clues? Cephalalgia 1992;12:178 – 9. 17. Schmoker JD, Terrien C 3rd, McPartland KJ, Boyum J, Wellman GC, Trombley L et al. Cerebrovascular response to continuous cold perfusion and hypothermic circulatory arrest. J Thorac Cardiovasc Surg 2009;137:459 –64. 18. Lipton RB, Lowenkopf T, Bajwa ZH, Leckie RS, Ribeiro S, Newman LC et al. Cardiac cephalgia: a treatable form of exertional headache. Neurology 1997;49:813 – 6.
Europace (2015) 17, 898–901 doi:10.1093/europace/euu321
Ablation for atrial fibrillation
Headache during cryoballoon ablation for atrial fibrillation Laurent Pison 1*, Pim Peeters 2, Yuri Blaauw 1, Kevin Vernooy 1, Narendra Kumar 1, Suzanne Philippens 1, Harry J. Crijns 1, Johan Vlaeyen 2, Jean Schoenen 3, and Carl Timmermans 1 1 Department of Cardiology, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands; 2Department of Psychology, KU Leuven, Leuven, Belgium; and 3Headache Research Unit, University Department of Neurology, CHR de la Citadelle, Lie`ge, Belgium
Received 23 July 2014; accepted after revision 1 November 2014
Aims
Headache has been reported to occur during cryoballoon ablation for atrial fibrillation (AF). No study has systematically analysed this phenomenon. ..................................................................................................................................................................................... Methods Twenty consecutive patients with symptomatic AF underwent cryoballoon ablation without sedation. Headache was and results evaluated before, during, and after the first cryoapplication in every pulmonary vein (PV) using a visual representation of a head for location of the headache, a numerical rating scale (NRS) for measuring pain intensity and the short-form McGill pain questionnaire (MPQ) for qualitative analysis of pain. The order in which the PVs were ablated was randomized. Sixteen (80%) patients perceived mainly frontal headache during cryoablation. The overall NRS scores were significantly higher during (5.1 + 1.7), compared with before (2.7 + 1.4), and after (3.5 + 2.2) a cryoapplication (P , 0.05). The NRS score was significantly higher during ablation of the first PV. The intensity of the perceived headache was not related to the temperature reached 150 s after initiation of a cryoapplication (P ¼ 0.81). Of the MPQ, three sensory adjectives and one affective adjective averaged between scores 1 and 2, representing mild-to-moderate severity of pain. ..................................................................................................................................................................................... Conclusion The majority of patients treated by balloon cryoablation experienced headache during a cryoapplication. There was no correlation between the temperature reached during a cryoballoon freeze and the intensity of the headache. Cryoballoon ablation of the first PV was significantly more painful than the remaining PVs.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Ablation † Atrial fibrillation † Headache † Cryoballoon
Introduction Pulmonary vein (PV) isolation, with the endpoint of complete electrical isolation, is the cornerstone in atrial fibrillation (AF) ablation.1 Radiofrequency (RF) is currently the most widespread energy source used to perform PV isolation. Pulmonary vein stenosis, atrio-oesophageal fistula, and left atrial flutter are some of the potential procedural complications that may occur using RF energy.2 – 4 Cryothermal energy is used to overcome several disadvantages of RF energy such as tissue disruption by excess heating and generation of inhomogeneous lesions.5 In a case–control study, cryoballoon ablation as an initial ablation technique for patients with paroxysmal AF resulted in less recurrences and a lower AF episode burden compared with RF energy.6 Point-by-point cryoablation is known to result in nearly no application-related pain.7 Several studies, however, reported headache during cryoballoon
ablation.8,9 The aetiology of this phenomenon is unknown. The purpose of this prospective study was to describe and quantify headache during cryoballoon ablation for AF.
Methods Study population Twenty consecutive patients with symptomatic AF (18 paroxysmal and 2 persistent) underwent cryoballoon ablation (Table 1).
Electrophysiological study Each patient gave informed consent. The study and data collection were performed according to a protocol approved by the Medical Ethical Committee of the Maastricht University Medical Centre. Via a femoral venous approach, a His bundle (St Jude Medical) and coronary sinus
* Corresponding author. Tel: +31 43 3877095; fax: +31 43 3875104, E-mail address: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
899
Headache during cryoballoon ablation
What’s new? † This is the first study to systematically analyse the occurrence of headache during cryoballoon ablation for atrial fibrillation. † The majority of patients treated by balloon cryoablation experience headache during a cryoapplication. † The precise aetiology of the headache occurring during cryoballoon ablation remains unclear.
catheter (Medtronic) were positioned in the heart. Via a double transseptal puncture under transoesophageal echocardiography guidance, a steerable 12F sheath (Flex Cath, Cryocath Technologies, Inc.) and a long 8F sheath (SL0, St Jude Medical) were advanced into the left atrium (LA). Thereafter, intravenous heparin was given as a 100 IU/kg bolus dose followed by a heparin infusion to keep an activated clotting time .300 s. During rapid ventricular pacing from the His bundle catheter, contrast was injected through the long sheath in the mid-portion of the LA to visualize all the ostia and major branches of the PVs. The PVs were mapped for the presence of potentials using a circular mapping catheter (Lasso, Biosense Webster) inserted in the LA through the long sheath. A cryoballoon (Arctic Front, Cryocath Technologies, Inc.) was introduced in the LA via the steerable sheath. In each PV, a single cryoballoon application of 5 min was given. The order in which the veins were ablated was randomized. During cryoablation of the right superior PV, diaphragmatic excursion was observed during continuous phrenic nerve stimulation using the His bundle catheter placed in the superior vena cava. Headache was evaluated before, 150 s after the start and after the first cryoapplication in each PV using a visual representation of a head for exact location of the headache, a numerical rating scale (NRS) for measuring pain intensity and the short-form McGill pain questionnaire (MPQ) for qualitative analysis of pain. Both measures are widely recognized as a valid and reliable instrument to quantify and characterize pain, with a Dutch language version available.10,11 The drawing of a head, the NRS, and the MPQ were shown to the patients using a commercially available, head-mounted display (I glassesTM , model PC3D Pro). The drawing of a head was subdivided in seven zones (Figure 1). In case of pain, the patient was requested to select the zone(s) where headache occurred. The NRS was numbered from 0 to 10; 0 represented no pain and 10 represented the maximum score for pain. All patients were instructed how to answer the questions of the MPQ before the start of the procedure. The questionnaire contains pain-descriptive words arranged in progressively increasing intensity and words describing the sensory, affective, and evaluative dimensions of pain. The list of words is scored accordingly to the method described by Melzack.10 After one application in every PV, we reassessed the presence of potentials and, where necessary, performed further cryoballoon applications until complete entrance block. If PV isolation could not be obtained after two cryoballoon applications, a conventional cryocatheter (Freezor Max, Cryocath Technologies, Inc.) was used. No sedation was administrated during the procedure.
veins were ablated, pain zone, and temperature of the cryoballoon were entered as independent, second-level, fixed variables. Separate analyses were conducted for the dependent variables: pain scores (NSR) and MPQ scores. A variance components matrix was chosen. A stepwise procedure was used where the model started out as an intercept-only model with one level, adding first a second level, then the fixed factors, and finally a random slope, provided that each next step made a significant contribution to the model. A step was considered a significant improvement based on a x2 significance test on the difference in 22 log likelihood (22LL) between the previous and new model.
Results Patient characteristics Apart from arterial hypertension, the patients had no structural heart disease. One patient underwent a previous cryoablation for typical atrial flutter. The clinical and echocardiographic characteristics of the patients are summarized in Table 1.
Procedural characteristics Each patient had four separate PVs and in all of those veins potentials were present prior to the first cryoballoon application. One patient was in AF at the start of the procedure. All PVs were successfully
Table 1 Clinical and echocardiographic characteristics Age (years)
59 + 11
Gender AF duration (months)
15 men 72 + 79
LA size (mm)
41 + 5
LVEF (%) AHT (n)
61 + 6 6
AAD/patient (n)
0.8 + 0.4
Persistent AF (n)
2
AAD, antiarrhythmic drugs; AF, atrial fibrillation; AHT, arterial hypertension; LA, left atrium; LVEF, left ventricular ejection fraction.
Statistical analysis Statistical analysis was performed using SPSS 16.0. Continuous variables are summarized with means and standard deviations. All the results were considered to be significant at P , 0.05. Multilevel regression analyses were conducted with participant as the first level of the analyses. The timing of the measurement (pre-/during/ post-ablation), the specific vein being ablated, the order in which the
Figure 1 Visual representation of a head, subdivided in seven zones.
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isolated with a mean of 6 + 2 (range 4– 11) complete cryoballoon applications per patient. In five patients (25%), a 23 mm cryoballoon was used. A conventional cryocatheter was used to ablate residual myocardial tissue in four right inferior PVs (range 1–7 applications). The mean temperature at 150 s after the start of a cryoballoon application was significantly lower in the right superior PV compared with the other PVs (P , 0.05). The mean duration of the procedure was 181 + 26 min and the mean fluoroscopy time was 58 + 19 min (Table 2). No complications occurred during the course of the study.
Analysis of headache variables Sixteen (80%) patients perceived headache during cryoablation. Headache scores ranged from 0 to 8. The headache was usually located on the forehead (zones 2, 3, 4, or 5) (Table 3). The analyses yielded a significant interaction effect between the timing of the measurement (before, during, or after cryoablation) and the order of the cryoablation (which PV was ablated first, second, third, or fourth) (P , 0.05). The overall NRS scores were significantly higher during (5.1 + 1.7), compared with before (2.7 + 1.4), and after (3.5 + 2.2) a cryoapplication (P , 0.05). This was also the case for the individual PVs. The NRS scores during ablation were significantly higher in the PV that was ablated first (5.7 + 1.6) compared with the other PVs, irrespective of which PV was ablated first (P , 0.05). The intensity of the perceived headache was not related to the temperature reached 150 s after the start of a cryoballoon freeze (P ¼ 0.81). One patient also reported chest pain during cryoablation. Of the MPQ, three sensory adjectives and one affective adjective averaged between scores 1 and 2, representing a mild-to-moderate severity of pain. The most common adjectives used by the patients to describe the head pain during the PV isolation were: aching (1.5 + 0.8), tender (1.4 + 0.8), tiring exhausting (1.2 + 0.9), and heavy (1.1 + 0.8). The other MPQ adjectives scored lower than one, representing no to mild severity of pain. The total MPQ sensory score was higher during (0.7 + 0.4) than pre-ablation (0.6 + 0.3), but the difference did not reach statistical significance (P ¼ 0.057).
Discussion Main findings The main finding of this study is that in the majority (80%) of patients with AF treated by balloon cryoablation, frontal headache occurred during a cryoapplication. There was no correlation between the temperature reached during a cryoballoon freeze and the intensity of the perceived headache. Cryoablation of the first PV, irrespective of its localization, was significantly more painful compared with cryoablation of the other three PVs. It has been shown that the use of cryothermal energy, as compared with RF energy, for ablation of the cavotricuspid isthmus, results in nearly no application-related pain.7 The use of a different catheter design adjusted to the ablation target, a conventional cryoablation catheter for ablation of the cavotricuspid isthmus vs. a cryoballoon for PV isolation, may contribute to the occurrence of pain during ablation. The occurrence of pain during PV isolation with the use of RF energy has been analysed in two studies.12,13 Radiofrequency energy application in the LA, however, results in chest pain and not headache. Chest pain occurred in up to 87.5% of the patients, although in both studies patients were maintained under moderate
Table 3 Headache variables before, during, and after a cryoapplication Pain localization (n)
9
Zone 1
9
Zone 2 Zone 3
42 47
Zone 4
32
Zone 5 Zone 6
13 7
Zone 7
10
Overall VAS score Before cryoapplication
2.7 + 1.4
During cryoapplication
5.1 + 1.7
After cryoapplication 3.5 + 2.2 VAS score before/during/after cryoapplication
Table 2 Cryoballoon ablation characteristics Number of cryoballoon applications/patient (n)
6+2
23/28 mm balloon
5/15
Mean temperature at 150 s after the start of an application (degrees celsius) LSPV LIPV RSPV RIPV Procedure duration (min) Fluoroscopy time (min)
244 + 7 245 + 7 250 + 7 240 + 10 181 + 26
First PV
1.0 + 1.4/5.7 + 1.6/3.2 + 1.4
Second PV Third PV
3.1 + 1.4/5.0 + 1.8/1.6 + 1.4 1.3 + 1.5/4.8 + 4.3/2.9 + 1.5
Fourth PV
1.0 + 1.5/4.3 + 1.6/2.9 + 1.5
VAS score before/during/after cryoapplication LSPV 3.0 + 1.0/5.7 + 1.6/2.6 + 1.6 LIPV
2.2 + 1.2/4.6 + 1.6/4.2 + 2.7
RSPV RIPV
3.2 + 0.8/4.3 + 1.0/2.2 + 1.3 3.1 + 1.8/5.6 + 2.0/4.3 + 1.9
Mean MPQ score (SD) before/during ablation MPQ sensory MPQ affective
0.56 (0.34)/0.73 (0.37) (P ¼ 0.057) 0.74 (0.76)/0.74 (0.70) (P ¼ 0.441)
58 + 19
LIPV, left inferior pulmonary vein; LSPV, left superior pulmonary vein; RIPV, right inferior pulmonary vein; RSPV, right superior pulmonary vein.
LIPV, left inferior pulmonary vein; LSPV, left superior pulmonary vein; MPQ, McGill pain questionnaire; PV, pulmonary vein; RIPV, right inferior pulmonary vein; RSPV, right superior pulmonary vein; VAS, visual analogue scale.
901
Headache during cryoballoon ablation
(‘conscious’) sedation throughout the procedure. The maximum temperature attained during a RF energy application showed a positive correlation with chest pain. Ablation at the left superior and inferior PV (especially the posterior and inferior aspects) resulted in significantly more pain than the other segments of the LA. The aetiology of chest pain during a RF energy application in the LA is not completely elucidated. One potential explanation includes the proximity of the ablation lesions to the oesophagus, resulting in tissue heating or deformation of the oesophageal wall, or the vascular and nerve plexus lining the oesophagus. The other explanations include the anatomic position of vagal and sympathetic afferents localized to the posterior wall and venoatrial junctions of the LA. Given that there is a large range in the headache report among the patients in this study, it is likely that the experience of pain during cryoballoon ablation is also influenced by individual differences.14 For example, we previously showed that differences in the personal meaning attached to the pain (such as pain catastrophizing) predicted the affective dimension of the pain reported during atrial cardioversion, despite the administration of a strong opioid (intranasal butorphanol tartrate).15 In future studies with cryoballoon ablation, we recommend to include such a measurement as well. Reducing catastrophizing thinking about pain through cognitive –behavioural techniques is likely to reduce pain levels, and may even increase the effectiveness of concomitant analgesics, when deemed necessary. The precise aetiology of the headache occurring during cryoballoon ablation is not well understood and we can only speculate on the possible underlying mechanisms. Vagal nerve stimulation in the mediastinum with referred pain is a possible explanation, but the pain is usually referred to the ipsilateral ear and teeth.16 Hypothermiainduced cerebral vasospasm has been reported during hypothermic circulatory arrest in cardiac surgery and is a plausible mechanism for headache during cryoballoon ablation.17 Cardiac cephalgia is less likely as it typically occurs during exertion in the setting of cardiac ischaemia and with unilateral headache.18 When explaining patients the course of a cryoballoon procedure not using general anaesthesia, physicians may inform their patients that headache may occur during cryoablation and reassure them that it concerns a transient phenomenon. If required, analgesics may be administrated.
Study limitations This study included a limited number of patients. But, as our intent was to describe and quantify headache during cryoballoon ablation, we consider our findings both interesting and valid in meeting our objectives. This is an observational study and it is therefore not possible to elaborate on causality. In this study, no individual psychological patient characteristics were measured. Another limitation of the study is that it was not sham-controlled, as no placebo applications were performed. Given the psychological implications of the pain perception, the anxiety of the patients due to their awareness that an application is being performed could modify the intensity and characteristics of the pain at that precise moment. Only simulating the application procedure without delivering cryoenergy could separate this effect from the real effects of the cooling.
Conclusion In the majority of patients with AF treated by balloon cryoablation, frontal headache occurred during and immediately after an application. Cryoablation of the first PV was significantly more painful compared with cryoablation of the other PVs. The underlying mechanism of headache during cryoballoon ablation remains unclear: potential mechanisms include vagal nerve stimulation, or hypothermia-induced cerebral vasospasm. Conflict of interest: none declared.
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