Original article
Atrioventricular conduction after alcohol septal ablation for obstructive hypertrophic cardiomyopathy Anna Axelssona, Kristina Weibringa, Ole Havndrupb, Henning Kelbæka, Erik Jørgensena, Steffen Helqvista, Kasper Iversena, Lars Købera, Henning Bundgaarda and Morten Kvistholm Jensena Aims Lesion of the atrioventricular conduction system is a well known adverse effect of alcohol septal ablation (ASA) in patients with obstructive hypertrophic cardiomyopathy (HCM). We assessed the atrioventricular conduction at longterm follow-up after ASA. Methods In patients with a pacemaker implanted for highgrade atrioventricular block after ASA, the atrioventricular conduction was assessed prospectively by ECGs and 48-h Holter recordings. In the remaining patients, the atrioventricular conduction was analysed retrospectively for comparison. Results A total of 24 (28%) of 87 patients with obstructive HCM without a pacemaker at baseline had a pacemaker implanted due to high-grade atrioventricular block after ASA. Ten of these patients were not available for follow-up. Holter recordings in the remaining 14 patients revealed normalized atrioventricular conduction in 6 patients 6.2 years (range 2.1–9.4) after ASA. Patients with high-grade atrioventricular block at follow-up had longer PR intervals at baseline [205 ms (200–230)] than the rest of the cohort [180 ms (140–200), P U 0.004] and a higher incidence of acute complete heart block (63 vs. 15%; P U 0.007) during ASA. A PR interval of at least 200 ms at baseline was associated with higher prevalence of high-grade
Introduction Alcohol septal ablation (ASA) was introduced in 1994 as a treatment option for patients with hypertrophic cardiomyopathy (HCM) with severe left-ventricular outflow (LVOT) obstruction and severe symptoms refractory to medical treatment.1 The short and longterm haemodynamic and symptomatic effects of ASA are well described.2–5 Lesion of the atrioventricular conduction system is a well-known adverse effect of ASA and the reported proportion of patients needing a permanent pacemaker implanted in relation to ASA is 3–38%.2–22 Transient or persistent complete heart block (CHB) develops acutely during the ablation in 14–64% of patients.2,5,9,14–16,18,19,23 Delayed CHB occurring hours to days after the procedure and late CHB occurring after months have also been described.2,5,14,16,23 –25 Identification of patients, in need of a permanent pacemaker, is challenging and relies on post-procedural continuous monitoring. On the basis of the knowledge from larger studies, the pacemaker implantation rate may be reduced 1558-2027 ß 2014 Italian Federation of Cardiology
atrioventricular block at follow-up (30 vs. 2%; P U 0.0013). The incidence of late-onset complete heart block was 1.5% per year after ASA. Conclusion We found normalized atrioventricular conduction at long-term follow-up, suggesting recovery in 6 of 14 patients with a pacemaker implanted in relation to ASA. Permanent atrioventricular conduction abnormalities were associated with baseline PR intervals of at least 200 ms and acute persistent complete heart block during ASA. J Cardiovasc Med 2014, 15:214–221 Keywords: alcohol septal ablation, atrioventricular block, hypertrophic cardiomyopathy, left-ventricular outflow obstruction, long-term follow-up, pacemaker a Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet & The University of Copenhagen and bDepartment of Cardiology, Roskilde Sygehus, Roskilde, Denmark
Correspondence to Anna Axelsson, MD, Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark Tel: +45 3545 2142; fax: +45 3545 7705; e-mail: [email protected] Received 14 December 2012 Revised 21 April 2013 Accepted 18 May 2013
to 8% at discharge, depending on patient selection and post-procedural routines.13 Whereas short-term recovery of atrioventricular conduction within hours or days after ASA is well documented,2,15,16 data determining potential long-term recovery of atrioventricular conduction are sparse.12–14,17,20,22 We assessed the atrioventricular conduction in a ASA-treated cohort at long-term follow-up.
Methods The present study is a combined prospective and retrospective study of atrioventricular conduction abnormalities in HCM patients treated with first-time ASA from January 1999 to March 2011 at the Department of Cardiology, Copenhagen University Hospital, Rigshospitalet. The study was performed in accordance with local ethical regulations and all patients gave informed consent. Septal ablation procedure
Indications for ASA were HCM and a LVOT gradient at least 50 mmHg at rest or at least 100 mmHg during stress DOI:10.2459/JCM.0b013e3283638073
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
Atrioventricular conduction after alcohol septal ablation Axelsson et al. 215
testing (exercise echocardiography or Valsalva manoeuvre) in combination with either severe, drug refractory dyspnoea [New York Heart Association (NYHA) class III–IV] or recurrent syncope. Prior to the procedure, a temporary pacing catheter was placed in the right ventricular apex in patients without a permanent pacemaker. Patients were monitored with continuous ECG and invasive blood pressure measurements during the procedure. The septal branch presumed to supply the obstructing part of the septum was first identified with coronary angiography. An over-the-wire balloon was placed in the septal branch and inflated. Radiographic contrast media were injected through the lumen of the balloon to ensure that there was no retrograde leak and the target septal branch had no collaterals. Secondly, echocardiographic contrast media (Levovist, Schering, Berlin, Germany; or Sonovue, Bracco Imaging, Milan, Italy) was injected through the balloon catheter into the target area during echocardiography to ensure that the septal branch supplied exclusively the obstructing part of the septum. When the target septal branch was safely identified, 96% ethanol was injected slowly at a rate of 1 ml/min through the inflated balloon catheter preventing retrograde flow of ethanol. On the basis of the growing evidence, the alcohol dose was reduced during the first years of experience to approximately 0.1 ml of alcohol per mm septum. An average amount of 2.4 0.8 ml 96% ethanol was injected into 1.1 0.2 septals. The balloon was kept inflated for 10 min after the injection of alcohol. CHB was seen in 38 (48%) patients during the procedure. Sustained ventricular tachycardia or ventricular fibrillation was seen in a total of 5 (6%) patients peri-procedure or post-procedure. Procedural characteristics are listed in Table 1. There were no procedure-related in-hospital deaths. Ten patients required a re-do procedure and one patient underwent two re-do procedures after 1 month and 7 years. Of these 11 patients, none needed a pacemaker after the first procedure, but two patients required a pacemaker after the re-do procedures.
temporary pacing catheter was removed 6 days (range 1–12) after the procedure if persisting high-grade atrioventricular block (second-degree atrioventricular block or CHB) was absent. Decisions on pacemaker implantations were taken after a median of 5 days (range 1–7) according to consensus between cardiologists from the subspecialties of HCM, interventional cardiology and electrophysiology. We defined acute CHB as CHB occurring in the catheterization laboratory. Acute, transient CHB was defined as acute CHB disappearing before leaving the catheterization laboratory and acute persistent CHB as acute CHB persisting when leaving the catheterization laboratory. Long-term evaluation of atrioventricular conduction
Patients with a permanent pacemaker implanted before discharge were included in the prospective long-term follow-up evaluation. A 12-lead ECG was obtained and rhythm, atrioventricular conduction and intra-ventricular conduction were analysed. In patients with no signs of high-grade atrioventricular block at the ECG the pacemaker/implantable cardioverter defibrillator (ICD) was adjusted to VVI mode and the lowest possible back-up, that is a frequency of 40/min, and the patient was monitored for 30 min. Pacemaker dependency was defined as any observation of high-grade atrioventricular block. If no high-grade atrioventricular block was seen after adjustment of the device, it was left in VVI-mode frequency 40/min and the patient was monitored for 48 h with an ambulatory Holter recording. If high-grade atrioventricular block was observed, the patient was considered pacemaker-dependent, and the device was adjusted to the previous settings and no further assessment was performed. The Holter recordings were analysed by an experienced technician and reviewed by a cardiologist. If high-grade atrioventricular block was observed in the Holter recording, the patient was considered pacemaker-dependent. The presence of tachyarrythmias was registered. In patients not available for follow-up and patients without a pacemaker, a retrospective analysis of the most recent ECG, Holter recording or pacemaker interrogation was performed.
Post-procedural monitoring and pacemaker implantation
Statistical analysis
Patients were monitored with telemetry and daily ECGs for at least 7 days after ASA in a coronary care unit. The
Statistical analysis was performed using SAS version 9.2 (Cary, North Carolina, USA). Data with a Gaussian
Table 1
Procedural characteristics of patients treated with first-time ASA stratified according to the requirement for PM implantation after
ASA Characteristics Septals ablated, n Volume of injected ethanol, ml Total acute AV block, n (%) Acute transient AV block, n (%) Acute persistent AV block, n (%) CK-MB maximum, mg/l
All patients (N ¼ 87)
No PM (n ¼ 63)
PM (n ¼ 24)
1.1 0.2 2.4 0.8 38 (48) 20 (25) 18 (23) 159 (110–231)
1.1 0.2 2.3 0.8 22 (37) 16 (27) 6 (10) 153 (106–231)
1.1 0.3 2.5 0.7 16 (76) 4 (19) 12 (57) 185 (147–230)
P 0.475 0.435 0.002 0.463 220
PR interval (ms) Prevalence of PM dependency at long-term follow-up after ASA (n ¼ 70) stratified according to the PR interval in baseline ECG. PM dependency was defined as documented second-degree AV block or third-degree AV block. In patients with atrial fibrillation or atrial flutter, bradycardia less than 40 beats/min or pauses of more than 1.5 s were considered equal to high-grade AV. ASA, alcohol septal ablation; AV, atrioventricular; PM, pacemaker.
high-grade atrioventricular block at follow-up compared to 9 of 61 patients with documented normal atrioventricular conduction (P ¼ 0.007) (Table 3). There were no significant differences in the amount of alcohol injected, the number of septal branches treated or maximum creatine kinase isoenzyme MB concentration after ASA.
Discussion To our knowledge the present study is the first long-term study of the atrioventricular conduction and factors associated with high-grade atrioventricular block at long-term follow-up in a cohort of patients with obstructive HCM treated with ASA. We found normal atrioventricular conduction, suggesting recovery of the atrioventricular conduction, in 6 of the 14 patients previously treated with a permanent pacemaker in relation to ASA. Our data showed the length of the PR interval in the baseline ECG to be associated with pacemaker dependency at follow-up. Few studies have assessed the pacemaker dependency after discharge and only two studies have reported assessment with continuous Holter recording. Faber et al.13 found complete recovery of atrioventricular conduction in 4 out of 11 patients at 3 months follow-up. In the series (n ¼ 26) of Guo et al.20 only one patient required a pacemaker. Three years later a 24-h Holter recording revealed recovery of atrioventricular conduction in this patient.20 Six other studies reported pacemaker dependency of 15– 93% of patients with a pacemaker implanted after ASA after a mean follow-up of up to 6 months.7,12,14,15,17,22 The methods used to assess the recovery of
The anatomical location of the ASA-induced infarction in the basal septum is close to the heart’s conduction system. Electrophysiological investigations performed by Lawrenz et al.14 suggested the location of the CHB during ASA to be located inside or distal to the His-bundle. In this study, the PR interval in the baseline ECG was associated with implantation of a pacemaker as well as with high-grade atrioventricular block at follow-up. This finding suggests a predisposing effect of an even mildly prolonged PR interval. The proximal bundle branches receive their blood supply from the atrioventricular node artery and the first septal branch, or either of them. The latter is often used for alcohol injection for ASA.26 Cui et al.27 found the distance from the first septal artery to the His-bundle to be less than 5 mm in 12.4% of the patients (n ¼ 105). Hence, this proximity to the atrioventricular conduction system may make it difficult to avoid atrioventricular conduction lesions in a considerable number of patients. Different strategies including reduction of alcohol quantity; combination of echo and pressure guidance; use of intra-procedural electrophysiologic testing and use of radiofrequency energy instead of alcohol in selected cases have been attempted to minimize lesions in the conduction system.10,14,23,28 –31 The treatment strategy may influence both outcome and complications. Mechanisms of acute or delayed conduction disturbances may be oedema together with ischaemic and toxic necrosis in the myocardium.13,32 Given that oedema may contribute to the conduction disturbances, it seems reasonable to believe that recovery of the atrioventricular conduction can be seen with time. Development of late CHB may be explained by myocardial scarring and fibrosis after ASA.13,19,22,23,32 Transient or persistent acute CHB occurring during ASA is well documented and seen in 14–64% of patients.2,5,9,14–16,18,19,23 We found CHB persisting when leaving the catheterization laboratory to be associated with both pacemaker implantation and high-grade atrioventricular block at long-term follow-up. Studies that differentiate between transient and persistent acute CHB report persistent CHB in 0–22% of patients.2,14–16 In the present study, we found acute persistent CHB in 23% of patients. The occurrence of sub-acute CHB hours to days after ASA is described in 1–25% of patients.5,14,16,23 –25 Late-onset CHB detected months after the procedure has also been reported.2,23 Kuhn
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220 Journal of Cardiovascular Medicine 2014, Vol 15 No 3
et al.23 found development of late-onset CHB in 2 of 172 patients after 11 and 24 months, respectively [mean follow-up of patients controlled for at least 1 year was 2.4 0.8 years (n ¼ 119)]. Seggewiss et al.2 found 2 of 100 patients to have developed late-onset second-degree atrioventricular block requiring pacemaker implantation after 4 and 8 months (mean follow-up 58 14 months). We found a comparable incidence of late-onset CHB in 3 (5%) of 63 patients after 2.3 years (range 0.3–11.9). It should be noted, however, that in HCM spontaneous development of fibrosis is seen in the hypertrophic septum.33 We found impaired atrioventricular conduction in 8 (10%) of 87 patients included in this study at baseline (firstdegree atrioventricular block in 7 patients and seconddegree atrioventricular block in 1 patient). In addition 2 of the 14 patients excluded from the study due to a device prior to ASA had the pacemaker implanted because of high-grade atrioventricular block (Fig. 1). Thus, atrioventricular conduction disturbances seem to be a part of the natural history of HCM. High-grade atrioventricular block occurring years after ASA may not be caused exclusively by the ASA-induced infarct, but rather in conjunction with HCM-related myocardial fibrosis and age-related impairment of the conduction system. Factors associated with pacemaker dependency
Previous studies have proposed age, female sex, firstdegree atrioventricular block or LBBB in baseline ECG, QRS-duration at baseline, acute conduction disturbances occurring during procedure, amount of alcohol injected, injection of a bolus of alcohol instead of continuous injection and injecting into more than one septal artery to be associated with CHB after ASA.7,11,13,14 Patients with LBBB in the baseline ECG have, in particular, been shown to be at high risk of developing CHB after ASA since the alcohol ablation mostly affects conduction in the right bundle branch. Faber et al.13 found that LBBB in baseline ECG resulted in 100% pacemaker dependency after ASA and proposed implantation of a pacemaker prior to the procedure when LBBB is seen in baseline ECG. The results in the present study are not consistent with the finding of Faber et al. Four patients in our population had LBBB in the baseline ECGs, but only two of these patients required a pacemaker after ASA. Consistent with earlier findings, however, we found age, PR interval and acute CHB persisting when leaving the catheterization laboratory to be associated with the implantation of a pacemaker.
atrioventricular recovery, but further studies are needed to determine the timing and likelihood of spontaneous recovery. The patients, who showed recovery at followup in this study, might have been identified shortly after ASA, if more sensitive observational routines were available. In conclusion, at long-term follow-up we found normalized atrioventricular conduction, suggesting recovery in 6 of 14 patients with a permanent pacemaker implanted in relation to ASA. This result illustrates the potential for late recovery of atrioventricular conduction in a considerable number of patients with high-grade atrioventricular block after ASA. Permanent conduction abnormalities were significantly associated with baseline PR intervals of at least 200 ms and acute persistent CHB during the procedure. This is important information that needs to be discussed with patients prior to the ASA procedure. The incidence of late-onset CHB after discharge was low. The results of the present study point out the need for further research in the timing of pacemaker implantation after ASA.
Acknowledgements Funding: Anna Axelsson received a travel grant from The Danish Heart Association (Hjerteforeningen) to present data at the European Society of Cardiology Congress 2012.
References 1 2
3 4
5
6
7
8
9
Limitations
The interpretation of our results is limited by the small number of patients. The fact that only 14 out of 24 patients with a pacemaker were able to participate in the follow-up may represent a bias. Furthermore, the atrioventricular conduction abnormalities could be paroxysmal and not detected in the 48-h Holter recordings. Thus, we document the existence of long-term
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11
Sigwart U. Nonsurgical myocardial reduction for hypertrophic obstructive cardiomyopathy. Lancet 1995; 346:211–214. Seggewiss H, Rigopoulos A, Welge D, et al. Long-term follow-up after percutaneous septal ablation in hypertrophic obstructive cardiomyopathy. Clin Res Cardiol 2007; 96:956–963. Sorajja P, Valeti U, Nishimura R, et al. Outcome of alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Circulation 2008; 118:131–139. Fernandes V, Nielsen C, Nagueh S, et al. Follow-up of alcohol septal ablation for symptomatic hypertrophic obstructive cardiomyopathy the Baylor and Medical University of South Carolina experience 1996 to 2007. JACC Cardiovasc Interv 2008; 1:561–570. Jensen M, Almaas V, Jacobsson L, et al. Long-term outcome of percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: a Scandinavian multicenter study. Circ Cardiovasc Interv 2011; 4:456–465. Veselka J, Zema´nek D, Tomasov P, et al. Complications of low-dose, echo-guided alcohol septal ablation. Catheter Cardiovasc Interv 2010; 75:546–550. Talreja D, Nishimura R, Edwards W, et al. Alcohol septal ablation versus surgical septal myectomy: comparison of effects on atrioventricular conduction tissue. J Am Coll Cardiol 2004; 44:2329–2332. Reinhard W, Ten Cate F, Scholten M, et al. Permanent pacing for complete atrioventricular block after nonsurgical (alcohol) septal reduction in patients with obstructive hypertrophic cardiomyopathy. Am J Cardiol 2004; 93:1964–1966. Li Z, Cheng T, Zhang W, et al. Percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy; The Chinese experience in 119 patients from a single center. Int J Cardiol 2004; 93:197–202. van der Lee C, Scholzel B, ten Berg J, et al. Usefulness of clinical, echocardiographic, and procedural characteristics to predict outcome after percutaneous transluminal septal myocardial ablation. Am J Cardiol 2008; 101:1315–1320. Chang S, Nagueh S, Spencer W 3rd, Lakkis N. Complete heart block: determinants and clinical impact in patients with hypertrophic obstructive cardiomyopathy undergoing nonsurgical septal reduction therapy. J Am Coll Cardiol 2003; 42:296–300.
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
Atrioventricular conduction after alcohol septal ablation Axelsson et al. 221
12
13
14
15
16
17
18
19
20
21
22
Kwon D, Kapadia S, Tuzcu E, et al. Long-term outcomes in high-risk symptomatic patients with hypertrophic cardiomyopathy undergoing alcohol septal ablation. JACC Cardiovasc Interv 2008; 1:432–438. Faber L, Welge D, Fassbender D, et al. Percutaneous septal ablation for symptomatic hypertrophic obstructive cardiomyopathy: managing the risk of procedure-related AV conduction disturbances. Int J Cardiol 2007; 119:163–167. Lawrenz T, Lieder F, Bartelsmeier M, et al. Predictors of complete heart block after transcoronary ablation of septal hypertrophy: results of a prospective electrophysiological investigation in 172 patients with hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 2007; 49:2356–2363. El-Jack S, Nasif M, Blake J, et al. Predictors of complete heart block after alcohol septal ablation for hypertrophic cardiomyopathy and the timing of pacemaker implantation. J Interv Cardiol 2007; 20:73–76. Chen A, Palacios I, Mela T, et al. Acute predictors of subacute complete heart block after alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Am J Cardiol 2006; 97:264–269. Lakkis N, Nagueh S, Dunn J, et al. Nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy: one-year follow-up. J Am Coll Cardiol 2000; 38:852–855. Faber L, Seggewiss H, Welge D, et al. Echo-guided percutaneous septal ablation for symptomatic hypertrophic obstructive cardiomyopathy: 7 years of experience. Eur J Echocardiogr 2004; 5:347–355. Gietzen F, Leuner C, Raute-Kreinsen U, et al. Acute and long-term results after transcoronary ablation of septal hypertrophy (TASH). Catheter interventional treatment for hypertrophic obstructive cardiomyopathy. Eur Heart J 1999; 20:1342–1354. Guo H, Wang P, Xing Y, et al. Delayed electrocardiographic changes after percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy. J Electrocardiol 2007; 40:356.e1–356.e6. Jensen M, Havndrup O, Hassager C, et al. Survival and sudden cardiac death after septal ablation for hypertrophic obstructive cardiomyopathy. Scand Cardiovasc J 2011; 45:153–160. Qin J, Shiota T, Lever H, et al. Conduction system abnormalities in patients with obstructive hypertrophic cardiomyopathy following septal reduction interventions. Am J Cardiol 2004; 93:171–175.
23
24
25 26 27
28
29
30
31
32
33
Kuhn H, Gietzen F, Leuner C, et al. Transcoronary ablation of septal hypertrophy (TASH): a new treatment option for hypertrophic obstructive cardiomyopathy. Z Kardiol 2000; 89 (Suppl 4IV):41–54. Kern M, Holmes D, Simpson C, et al. Delayed occurrence of complete heart block without warning after alcohol septal ablation for hypertrophic obstructive cardiomyopathy. Catheter Cardiovasc Interv 2002; 56:503– 507. Kuhn H, Seggewiss H, Gietzen F, et al. Catheter-based therapy for hypertrophic obstructive cardiomyopathy. Z Kardiol 2004; 93:23–31. Frink R, James T. Normal blood supply to the human His bundle and proximal bundle branches. Circulation 1973; 47:8–18. Cui W, Liu F, Zu X, et al. The relation between His bundle and the first septal perforating artery: implications for percutaneous transluminal septal myocardial ablation. Int J Cardiol 2004; 97:579–580. Lawrenz T, Borchert B, Leuner C, et al. Endocardial radiofrequency ablation for hypertrophic obstructive cardiomyopathy: acute results and 6 months’ follow-up in 19 patients. J Am Coll Cardiol 2011; 57:572–576. [Epub 2011/01/29] Veselka J, Tomasov P, Zemanek D. Long-term effects of varying alcohol dosing in percutaneous septal ablation for obstructive hypertrophic cardiomyopathy: a randomized study with a follow-up up to 11 years. Can J Cardiol 2011; 27:763–767. [Epub 2011/10/18] Gimeno JR, Tome MT, McKenna WJ. Alcohol septal ablation in hypertrophic cardiomyopathy: an opportunity to be taken. Rev Esp Cardiol (Engl Ed) 2012; 65:314–318. [Epub 2012/03/03] Sorajja P, Binder J, Nishimura RA, et al. Predictors of an optimal clinical outcome with alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Catheter Cardiovasc Interv 2013; 81:E58–E67. [Epub 2012/04/19] Raute-Kreinsen U. Morphology of necrosis and repair after transcoronary ethanol ablation of septal hypertrophy. Pathol Res Pract 2003; 199:121– 127. Almaas V, Haugaa K, Strøm E, et al. Increased amount of interstitial fibrosis predicts ventricular arrhythmias, and is associated with reduced myocardial septal function in patients with obstructive hypertrophic cardiomyopathy. Europace 2013. [Epub ahead of print]
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
Atrioventricular conduction after alcohol septal ablation for obstructive hypertrophic cardiomyopathy Anna Axelssona, Kristina Weibringa, Ole Havndrupb, Henning Kelbæka, Erik Jørgensena, Steffen Helqvista, Kasper Iversena, Lars Købera, Henning Bundgaarda and Morten Kvistholm Jensena Aims Lesion of the atrioventricular conduction system is a well known adverse effect of alcohol septal ablation (ASA) in patients with obstructive hypertrophic cardiomyopathy (HCM). We assessed the atrioventricular conduction at longterm follow-up after ASA. Methods In patients with a pacemaker implanted for highgrade atrioventricular block after ASA, the atrioventricular conduction was assessed prospectively by ECGs and 48-h Holter recordings. In the remaining patients, the atrioventricular conduction was analysed retrospectively for comparison. Results A total of 24 (28%) of 87 patients with obstructive HCM without a pacemaker at baseline had a pacemaker implanted due to high-grade atrioventricular block after ASA. Ten of these patients were not available for follow-up. Holter recordings in the remaining 14 patients revealed normalized atrioventricular conduction in 6 patients 6.2 years (range 2.1–9.4) after ASA. Patients with high-grade atrioventricular block at follow-up had longer PR intervals at baseline [205 ms (200–230)] than the rest of the cohort [180 ms (140–200), P U 0.004] and a higher incidence of acute complete heart block (63 vs. 15%; P U 0.007) during ASA. A PR interval of at least 200 ms at baseline was associated with higher prevalence of high-grade
Introduction Alcohol septal ablation (ASA) was introduced in 1994 as a treatment option for patients with hypertrophic cardiomyopathy (HCM) with severe left-ventricular outflow (LVOT) obstruction and severe symptoms refractory to medical treatment.1 The short and longterm haemodynamic and symptomatic effects of ASA are well described.2–5 Lesion of the atrioventricular conduction system is a well-known adverse effect of ASA and the reported proportion of patients needing a permanent pacemaker implanted in relation to ASA is 3–38%.2–22 Transient or persistent complete heart block (CHB) develops acutely during the ablation in 14–64% of patients.2,5,9,14–16,18,19,23 Delayed CHB occurring hours to days after the procedure and late CHB occurring after months have also been described.2,5,14,16,23 –25 Identification of patients, in need of a permanent pacemaker, is challenging and relies on post-procedural continuous monitoring. On the basis of the knowledge from larger studies, the pacemaker implantation rate may be reduced 1558-2027 ß 2014 Italian Federation of Cardiology
atrioventricular block at follow-up (30 vs. 2%; P U 0.0013). The incidence of late-onset complete heart block was 1.5% per year after ASA. Conclusion We found normalized atrioventricular conduction at long-term follow-up, suggesting recovery in 6 of 14 patients with a pacemaker implanted in relation to ASA. Permanent atrioventricular conduction abnormalities were associated with baseline PR intervals of at least 200 ms and acute persistent complete heart block during ASA. J Cardiovasc Med 2014, 15:214–221 Keywords: alcohol septal ablation, atrioventricular block, hypertrophic cardiomyopathy, left-ventricular outflow obstruction, long-term follow-up, pacemaker a Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet & The University of Copenhagen and bDepartment of Cardiology, Roskilde Sygehus, Roskilde, Denmark
Correspondence to Anna Axelsson, MD, Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark Tel: +45 3545 2142; fax: +45 3545 7705; e-mail: [email protected] Received 14 December 2012 Revised 21 April 2013 Accepted 18 May 2013
to 8% at discharge, depending on patient selection and post-procedural routines.13 Whereas short-term recovery of atrioventricular conduction within hours or days after ASA is well documented,2,15,16 data determining potential long-term recovery of atrioventricular conduction are sparse.12–14,17,20,22 We assessed the atrioventricular conduction in a ASA-treated cohort at long-term follow-up.
Methods The present study is a combined prospective and retrospective study of atrioventricular conduction abnormalities in HCM patients treated with first-time ASA from January 1999 to March 2011 at the Department of Cardiology, Copenhagen University Hospital, Rigshospitalet. The study was performed in accordance with local ethical regulations and all patients gave informed consent. Septal ablation procedure
Indications for ASA were HCM and a LVOT gradient at least 50 mmHg at rest or at least 100 mmHg during stress DOI:10.2459/JCM.0b013e3283638073
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
Atrioventricular conduction after alcohol septal ablation Axelsson et al. 215
testing (exercise echocardiography or Valsalva manoeuvre) in combination with either severe, drug refractory dyspnoea [New York Heart Association (NYHA) class III–IV] or recurrent syncope. Prior to the procedure, a temporary pacing catheter was placed in the right ventricular apex in patients without a permanent pacemaker. Patients were monitored with continuous ECG and invasive blood pressure measurements during the procedure. The septal branch presumed to supply the obstructing part of the septum was first identified with coronary angiography. An over-the-wire balloon was placed in the septal branch and inflated. Radiographic contrast media were injected through the lumen of the balloon to ensure that there was no retrograde leak and the target septal branch had no collaterals. Secondly, echocardiographic contrast media (Levovist, Schering, Berlin, Germany; or Sonovue, Bracco Imaging, Milan, Italy) was injected through the balloon catheter into the target area during echocardiography to ensure that the septal branch supplied exclusively the obstructing part of the septum. When the target septal branch was safely identified, 96% ethanol was injected slowly at a rate of 1 ml/min through the inflated balloon catheter preventing retrograde flow of ethanol. On the basis of the growing evidence, the alcohol dose was reduced during the first years of experience to approximately 0.1 ml of alcohol per mm septum. An average amount of 2.4 0.8 ml 96% ethanol was injected into 1.1 0.2 septals. The balloon was kept inflated for 10 min after the injection of alcohol. CHB was seen in 38 (48%) patients during the procedure. Sustained ventricular tachycardia or ventricular fibrillation was seen in a total of 5 (6%) patients peri-procedure or post-procedure. Procedural characteristics are listed in Table 1. There were no procedure-related in-hospital deaths. Ten patients required a re-do procedure and one patient underwent two re-do procedures after 1 month and 7 years. Of these 11 patients, none needed a pacemaker after the first procedure, but two patients required a pacemaker after the re-do procedures.
temporary pacing catheter was removed 6 days (range 1–12) after the procedure if persisting high-grade atrioventricular block (second-degree atrioventricular block or CHB) was absent. Decisions on pacemaker implantations were taken after a median of 5 days (range 1–7) according to consensus between cardiologists from the subspecialties of HCM, interventional cardiology and electrophysiology. We defined acute CHB as CHB occurring in the catheterization laboratory. Acute, transient CHB was defined as acute CHB disappearing before leaving the catheterization laboratory and acute persistent CHB as acute CHB persisting when leaving the catheterization laboratory. Long-term evaluation of atrioventricular conduction
Patients with a permanent pacemaker implanted before discharge were included in the prospective long-term follow-up evaluation. A 12-lead ECG was obtained and rhythm, atrioventricular conduction and intra-ventricular conduction were analysed. In patients with no signs of high-grade atrioventricular block at the ECG the pacemaker/implantable cardioverter defibrillator (ICD) was adjusted to VVI mode and the lowest possible back-up, that is a frequency of 40/min, and the patient was monitored for 30 min. Pacemaker dependency was defined as any observation of high-grade atrioventricular block. If no high-grade atrioventricular block was seen after adjustment of the device, it was left in VVI-mode frequency 40/min and the patient was monitored for 48 h with an ambulatory Holter recording. If high-grade atrioventricular block was observed, the patient was considered pacemaker-dependent, and the device was adjusted to the previous settings and no further assessment was performed. The Holter recordings were analysed by an experienced technician and reviewed by a cardiologist. If high-grade atrioventricular block was observed in the Holter recording, the patient was considered pacemaker-dependent. The presence of tachyarrythmias was registered. In patients not available for follow-up and patients without a pacemaker, a retrospective analysis of the most recent ECG, Holter recording or pacemaker interrogation was performed.
Post-procedural monitoring and pacemaker implantation
Statistical analysis
Patients were monitored with telemetry and daily ECGs for at least 7 days after ASA in a coronary care unit. The
Statistical analysis was performed using SAS version 9.2 (Cary, North Carolina, USA). Data with a Gaussian
Table 1
Procedural characteristics of patients treated with first-time ASA stratified according to the requirement for PM implantation after
ASA Characteristics Septals ablated, n Volume of injected ethanol, ml Total acute AV block, n (%) Acute transient AV block, n (%) Acute persistent AV block, n (%) CK-MB maximum, mg/l
All patients (N ¼ 87)
No PM (n ¼ 63)
PM (n ¼ 24)
1.1 0.2 2.4 0.8 38 (48) 20 (25) 18 (23) 159 (110–231)
1.1 0.2 2.3 0.8 22 (37) 16 (27) 6 (10) 153 (106–231)
1.1 0.3 2.5 0.7 16 (76) 4 (19) 12 (57) 185 (147–230)
P 0.475 0.435 0.002 0.463 220
PR interval (ms) Prevalence of PM dependency at long-term follow-up after ASA (n ¼ 70) stratified according to the PR interval in baseline ECG. PM dependency was defined as documented second-degree AV block or third-degree AV block. In patients with atrial fibrillation or atrial flutter, bradycardia less than 40 beats/min or pauses of more than 1.5 s were considered equal to high-grade AV. ASA, alcohol septal ablation; AV, atrioventricular; PM, pacemaker.
high-grade atrioventricular block at follow-up compared to 9 of 61 patients with documented normal atrioventricular conduction (P ¼ 0.007) (Table 3). There were no significant differences in the amount of alcohol injected, the number of septal branches treated or maximum creatine kinase isoenzyme MB concentration after ASA.
Discussion To our knowledge the present study is the first long-term study of the atrioventricular conduction and factors associated with high-grade atrioventricular block at long-term follow-up in a cohort of patients with obstructive HCM treated with ASA. We found normal atrioventricular conduction, suggesting recovery of the atrioventricular conduction, in 6 of the 14 patients previously treated with a permanent pacemaker in relation to ASA. Our data showed the length of the PR interval in the baseline ECG to be associated with pacemaker dependency at follow-up. Few studies have assessed the pacemaker dependency after discharge and only two studies have reported assessment with continuous Holter recording. Faber et al.13 found complete recovery of atrioventricular conduction in 4 out of 11 patients at 3 months follow-up. In the series (n ¼ 26) of Guo et al.20 only one patient required a pacemaker. Three years later a 24-h Holter recording revealed recovery of atrioventricular conduction in this patient.20 Six other studies reported pacemaker dependency of 15– 93% of patients with a pacemaker implanted after ASA after a mean follow-up of up to 6 months.7,12,14,15,17,22 The methods used to assess the recovery of
The anatomical location of the ASA-induced infarction in the basal septum is close to the heart’s conduction system. Electrophysiological investigations performed by Lawrenz et al.14 suggested the location of the CHB during ASA to be located inside or distal to the His-bundle. In this study, the PR interval in the baseline ECG was associated with implantation of a pacemaker as well as with high-grade atrioventricular block at follow-up. This finding suggests a predisposing effect of an even mildly prolonged PR interval. The proximal bundle branches receive their blood supply from the atrioventricular node artery and the first septal branch, or either of them. The latter is often used for alcohol injection for ASA.26 Cui et al.27 found the distance from the first septal artery to the His-bundle to be less than 5 mm in 12.4% of the patients (n ¼ 105). Hence, this proximity to the atrioventricular conduction system may make it difficult to avoid atrioventricular conduction lesions in a considerable number of patients. Different strategies including reduction of alcohol quantity; combination of echo and pressure guidance; use of intra-procedural electrophysiologic testing and use of radiofrequency energy instead of alcohol in selected cases have been attempted to minimize lesions in the conduction system.10,14,23,28 –31 The treatment strategy may influence both outcome and complications. Mechanisms of acute or delayed conduction disturbances may be oedema together with ischaemic and toxic necrosis in the myocardium.13,32 Given that oedema may contribute to the conduction disturbances, it seems reasonable to believe that recovery of the atrioventricular conduction can be seen with time. Development of late CHB may be explained by myocardial scarring and fibrosis after ASA.13,19,22,23,32 Transient or persistent acute CHB occurring during ASA is well documented and seen in 14–64% of patients.2,5,9,14–16,18,19,23 We found CHB persisting when leaving the catheterization laboratory to be associated with both pacemaker implantation and high-grade atrioventricular block at long-term follow-up. Studies that differentiate between transient and persistent acute CHB report persistent CHB in 0–22% of patients.2,14–16 In the present study, we found acute persistent CHB in 23% of patients. The occurrence of sub-acute CHB hours to days after ASA is described in 1–25% of patients.5,14,16,23 –25 Late-onset CHB detected months after the procedure has also been reported.2,23 Kuhn
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220 Journal of Cardiovascular Medicine 2014, Vol 15 No 3
et al.23 found development of late-onset CHB in 2 of 172 patients after 11 and 24 months, respectively [mean follow-up of patients controlled for at least 1 year was 2.4 0.8 years (n ¼ 119)]. Seggewiss et al.2 found 2 of 100 patients to have developed late-onset second-degree atrioventricular block requiring pacemaker implantation after 4 and 8 months (mean follow-up 58 14 months). We found a comparable incidence of late-onset CHB in 3 (5%) of 63 patients after 2.3 years (range 0.3–11.9). It should be noted, however, that in HCM spontaneous development of fibrosis is seen in the hypertrophic septum.33 We found impaired atrioventricular conduction in 8 (10%) of 87 patients included in this study at baseline (firstdegree atrioventricular block in 7 patients and seconddegree atrioventricular block in 1 patient). In addition 2 of the 14 patients excluded from the study due to a device prior to ASA had the pacemaker implanted because of high-grade atrioventricular block (Fig. 1). Thus, atrioventricular conduction disturbances seem to be a part of the natural history of HCM. High-grade atrioventricular block occurring years after ASA may not be caused exclusively by the ASA-induced infarct, but rather in conjunction with HCM-related myocardial fibrosis and age-related impairment of the conduction system. Factors associated with pacemaker dependency
Previous studies have proposed age, female sex, firstdegree atrioventricular block or LBBB in baseline ECG, QRS-duration at baseline, acute conduction disturbances occurring during procedure, amount of alcohol injected, injection of a bolus of alcohol instead of continuous injection and injecting into more than one septal artery to be associated with CHB after ASA.7,11,13,14 Patients with LBBB in the baseline ECG have, in particular, been shown to be at high risk of developing CHB after ASA since the alcohol ablation mostly affects conduction in the right bundle branch. Faber et al.13 found that LBBB in baseline ECG resulted in 100% pacemaker dependency after ASA and proposed implantation of a pacemaker prior to the procedure when LBBB is seen in baseline ECG. The results in the present study are not consistent with the finding of Faber et al. Four patients in our population had LBBB in the baseline ECGs, but only two of these patients required a pacemaker after ASA. Consistent with earlier findings, however, we found age, PR interval and acute CHB persisting when leaving the catheterization laboratory to be associated with the implantation of a pacemaker.
atrioventricular recovery, but further studies are needed to determine the timing and likelihood of spontaneous recovery. The patients, who showed recovery at followup in this study, might have been identified shortly after ASA, if more sensitive observational routines were available. In conclusion, at long-term follow-up we found normalized atrioventricular conduction, suggesting recovery in 6 of 14 patients with a permanent pacemaker implanted in relation to ASA. This result illustrates the potential for late recovery of atrioventricular conduction in a considerable number of patients with high-grade atrioventricular block after ASA. Permanent conduction abnormalities were significantly associated with baseline PR intervals of at least 200 ms and acute persistent CHB during the procedure. This is important information that needs to be discussed with patients prior to the ASA procedure. The incidence of late-onset CHB after discharge was low. The results of the present study point out the need for further research in the timing of pacemaker implantation after ASA.
Acknowledgements Funding: Anna Axelsson received a travel grant from The Danish Heart Association (Hjerteforeningen) to present data at the European Society of Cardiology Congress 2012.
References 1 2
3 4
5
6
7
8
9
Limitations
The interpretation of our results is limited by the small number of patients. The fact that only 14 out of 24 patients with a pacemaker were able to participate in the follow-up may represent a bias. Furthermore, the atrioventricular conduction abnormalities could be paroxysmal and not detected in the 48-h Holter recordings. Thus, we document the existence of long-term
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Sigwart U. Nonsurgical myocardial reduction for hypertrophic obstructive cardiomyopathy. Lancet 1995; 346:211–214. Seggewiss H, Rigopoulos A, Welge D, et al. Long-term follow-up after percutaneous septal ablation in hypertrophic obstructive cardiomyopathy. Clin Res Cardiol 2007; 96:956–963. Sorajja P, Valeti U, Nishimura R, et al. Outcome of alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Circulation 2008; 118:131–139. Fernandes V, Nielsen C, Nagueh S, et al. Follow-up of alcohol septal ablation for symptomatic hypertrophic obstructive cardiomyopathy the Baylor and Medical University of South Carolina experience 1996 to 2007. JACC Cardiovasc Interv 2008; 1:561–570. Jensen M, Almaas V, Jacobsson L, et al. Long-term outcome of percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: a Scandinavian multicenter study. Circ Cardiovasc Interv 2011; 4:456–465. Veselka J, Zema´nek D, Tomasov P, et al. Complications of low-dose, echo-guided alcohol septal ablation. Catheter Cardiovasc Interv 2010; 75:546–550. Talreja D, Nishimura R, Edwards W, et al. Alcohol septal ablation versus surgical septal myectomy: comparison of effects on atrioventricular conduction tissue. J Am Coll Cardiol 2004; 44:2329–2332. Reinhard W, Ten Cate F, Scholten M, et al. Permanent pacing for complete atrioventricular block after nonsurgical (alcohol) septal reduction in patients with obstructive hypertrophic cardiomyopathy. Am J Cardiol 2004; 93:1964–1966. Li Z, Cheng T, Zhang W, et al. Percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy; The Chinese experience in 119 patients from a single center. Int J Cardiol 2004; 93:197–202. van der Lee C, Scholzel B, ten Berg J, et al. Usefulness of clinical, echocardiographic, and procedural characteristics to predict outcome after percutaneous transluminal septal myocardial ablation. Am J Cardiol 2008; 101:1315–1320. Chang S, Nagueh S, Spencer W 3rd, Lakkis N. Complete heart block: determinants and clinical impact in patients with hypertrophic obstructive cardiomyopathy undergoing nonsurgical septal reduction therapy. J Am Coll Cardiol 2003; 42:296–300.
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
Atrioventricular conduction after alcohol septal ablation Axelsson et al. 221
12
13
14
15
16
17
18
19
20
21
22
Kwon D, Kapadia S, Tuzcu E, et al. Long-term outcomes in high-risk symptomatic patients with hypertrophic cardiomyopathy undergoing alcohol septal ablation. JACC Cardiovasc Interv 2008; 1:432–438. Faber L, Welge D, Fassbender D, et al. Percutaneous septal ablation for symptomatic hypertrophic obstructive cardiomyopathy: managing the risk of procedure-related AV conduction disturbances. Int J Cardiol 2007; 119:163–167. Lawrenz T, Lieder F, Bartelsmeier M, et al. Predictors of complete heart block after transcoronary ablation of septal hypertrophy: results of a prospective electrophysiological investigation in 172 patients with hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 2007; 49:2356–2363. El-Jack S, Nasif M, Blake J, et al. Predictors of complete heart block after alcohol septal ablation for hypertrophic cardiomyopathy and the timing of pacemaker implantation. J Interv Cardiol 2007; 20:73–76. Chen A, Palacios I, Mela T, et al. Acute predictors of subacute complete heart block after alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Am J Cardiol 2006; 97:264–269. Lakkis N, Nagueh S, Dunn J, et al. Nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy: one-year follow-up. J Am Coll Cardiol 2000; 38:852–855. Faber L, Seggewiss H, Welge D, et al. Echo-guided percutaneous septal ablation for symptomatic hypertrophic obstructive cardiomyopathy: 7 years of experience. Eur J Echocardiogr 2004; 5:347–355. Gietzen F, Leuner C, Raute-Kreinsen U, et al. Acute and long-term results after transcoronary ablation of septal hypertrophy (TASH). Catheter interventional treatment for hypertrophic obstructive cardiomyopathy. Eur Heart J 1999; 20:1342–1354. Guo H, Wang P, Xing Y, et al. Delayed electrocardiographic changes after percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy. J Electrocardiol 2007; 40:356.e1–356.e6. Jensen M, Havndrup O, Hassager C, et al. Survival and sudden cardiac death after septal ablation for hypertrophic obstructive cardiomyopathy. Scand Cardiovasc J 2011; 45:153–160. Qin J, Shiota T, Lever H, et al. Conduction system abnormalities in patients with obstructive hypertrophic cardiomyopathy following septal reduction interventions. Am J Cardiol 2004; 93:171–175.
23
24
25 26 27
28
29
30
31
32
33
Kuhn H, Gietzen F, Leuner C, et al. Transcoronary ablation of septal hypertrophy (TASH): a new treatment option for hypertrophic obstructive cardiomyopathy. Z Kardiol 2000; 89 (Suppl 4IV):41–54. Kern M, Holmes D, Simpson C, et al. Delayed occurrence of complete heart block without warning after alcohol septal ablation for hypertrophic obstructive cardiomyopathy. Catheter Cardiovasc Interv 2002; 56:503– 507. Kuhn H, Seggewiss H, Gietzen F, et al. Catheter-based therapy for hypertrophic obstructive cardiomyopathy. Z Kardiol 2004; 93:23–31. Frink R, James T. Normal blood supply to the human His bundle and proximal bundle branches. Circulation 1973; 47:8–18. Cui W, Liu F, Zu X, et al. The relation between His bundle and the first septal perforating artery: implications for percutaneous transluminal septal myocardial ablation. Int J Cardiol 2004; 97:579–580. Lawrenz T, Borchert B, Leuner C, et al. Endocardial radiofrequency ablation for hypertrophic obstructive cardiomyopathy: acute results and 6 months’ follow-up in 19 patients. J Am Coll Cardiol 2011; 57:572–576. [Epub 2011/01/29] Veselka J, Tomasov P, Zemanek D. Long-term effects of varying alcohol dosing in percutaneous septal ablation for obstructive hypertrophic cardiomyopathy: a randomized study with a follow-up up to 11 years. Can J Cardiol 2011; 27:763–767. [Epub 2011/10/18] Gimeno JR, Tome MT, McKenna WJ. Alcohol septal ablation in hypertrophic cardiomyopathy: an opportunity to be taken. Rev Esp Cardiol (Engl Ed) 2012; 65:314–318. [Epub 2012/03/03] Sorajja P, Binder J, Nishimura RA, et al. Predictors of an optimal clinical outcome with alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Catheter Cardiovasc Interv 2013; 81:E58–E67. [Epub 2012/04/19] Raute-Kreinsen U. Morphology of necrosis and repair after transcoronary ethanol ablation of septal hypertrophy. Pathol Res Pract 2003; 199:121– 127. Almaas V, Haugaa K, Strøm E, et al. Increased amount of interstitial fibrosis predicts ventricular arrhythmias, and is associated with reduced myocardial septal function in patients with obstructive hypertrophic cardiomyopathy. Europace 2013. [Epub ahead of print]
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