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Historical Milestones and Progress in the Research on Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy
Canadian Journal of Cardiology 30 (2014) 46e51
Review
Historical Milestones and Progress in the Research on Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy Josef Veselka, MD, PhD Department of Cardiology, 2nd Medical School, Charles University and University Hospital Motol, Prague, Czech Republic
ABSTRACT
RESUM E
The first alcohol septal ablation was performed almost 20 years ago in 1994; since then it has become a widely used technique for the treatment of highly symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). It has been shown that postprocedural basal septal shrinking as a result of myocardial scarring is followed by a decrease in left ventricular (LV) obstruction, regression of LV hypertrophy within the first postprocedural year, improvement of diastolic function, and reduction of the degree of mitral regurgitation. All these changes are accompanied by significant symptom relief. Although there is only limited evidence of postprocedural long-term survival, all the studies presented here are consistent in the low incidence of sudden death and similar prognoses with an age- and sex-matched general population. Conversely, we still have to be aware that a certain knowledge gap exists with regard to postprocedural longterm outcome. Therefore, careful selection of patients for alcohol septal ablation is needed, and all patients should be treated in centres offering all therapeutic options.
te re alise e il y a presque 20 La première ablation septale à l’alcool a e e dans le ans, en 1994. Depuis, elle est une technique très utilise traitement des patients fortement symptomatiques ayant une car te de montre diomyopathie hypertrophique obstructive (CMHO). Il a e tre cissement postinterventionnel du septum basal à la suite que le re de la cicatrisation du myocarde est suivi d’une diminution de l’obgression de l’hypertrophie struction du ventricule gauche, de la re e après l’intervenventriculaire gauche au cours de la première anne lioration du fonctionnement diastolique et de la tion, de l’ame duction du degre de la re gurgitation mitrale. Tous ces changements re s d’un soulagement significatif des symptômes. Bien sont accompagne es scientifiques sur la survie à long qu’il n’existe que peu de donne tudes publie es confirment la terme après l’intervention, toutes les e quence de mort subite et de pronostics similaires sur une faible fre ne rale apparie e selon l’âge et le sexe. En contrepartie, population ge nous devons demeurer conscients du fait qu’il existe un certain manvolution à long terme après que de connaissance en ce qui concerne l’e lection rigoureuse des patients qui subiront l’intervention. Ainsi, une se cessaire, et tous les patients del’ablation septale à l’alcool est ne s dans des centres offrant toutes les options vraient être traite rapeutiques. the
Historical Introduction Hypertrophic cardiomyopathy (HCM) is characterized by unexplained hypertrophy of the left (or also right) ventricle in the absence of another disease that would be capable of producing the magnitude of hypertrophy in a given patient and is mostly caused by an autosomal dominant mutation in genes encoding sarcomere or sarcomere-associated proteins.1 Approximately two thirds of patients have significant left ventricular (LV) obstruction at rest ( 30 mm Hg) or at physiologic provocation ( 50 mm Hg).1 Outflow obstruc
tion is responsible for increased LV systolic pressure, which consequently leads to myocardial ischemia, mitral regurgitation, and impairment of diastolic and systolic function. All this eventually leads to pulmonary hypertension and congestive heart failure. Therefore, highly symptomatic patients who have a large LV gradient and do not respond to medical therapy have been considered the best candidates for surgical myectomy. In the early 1960s, several surgical centres began performing septal myectomy with the removal of a small amount of muscle (5 to 10 g) from the basal septum2,3 Also, mitral valve replacement was used as an alternative therapy in selected patients to eliminate subaortic obstruction, but it is not an acceptable therapeutic approach now. According to the only American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guideline for the diagnosis and treatment of HCM, surgical myectomy is still the “firstoption” and “gold standard” therapy of hypertrophic obstructive cardiomyopathy (HOCM).1
Received for publication September 15, 2013. Accepted October 1, 2013. Corresponding author: Dr Josef Veselka, Department of Cardiology, V úvalu 84, Prague 5, 15000, Czech Republic. Tel.: þ420224434900; fax: þ420224434920. E-mail: [email protected] See page 50 for disclosure information.
0828-282X/$ - see front matter Ó 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cjca.2013.10.001
Josef Veselka Alcohol Septal Ablation
The development of interventional cardiology in the 1980s and 1990s of the past century led to attempts to eliminate LV obstruction by catheter-based techniques, consequently decreasing the morbidity and mortality of HOCM. The idea of inducing septal infarction by catheter techniques was primarily suggested by the observation that myocardial function of selected areas of the left ventricle can be suppressed by balloon occlusion of the supplying artery during angioplasty. The outflow gradient in HOCM decreased significantly when the first septal artery was temporarily occluded by an angioplasty balloon catheter.4-6 The suggestion to use alcohol for permanent ablation of a hypertrophic septum was likely derived from Brugada et al.’s work dealing with the treatment of ventricular arrhythmias by intracoronary alcohol injection.7 At least 2 groups of researchers, almost at the same time, progressed rapidly to alcohol ablation for HOCM. Gietzen et al. presented their preliminary results at the Annual Congress of the German Cardiac Society in April 1994,8 and Sigwart et al. performed the first alcohol septal ablation (ASA), which was called at that time “nonsurgical myocardial reduction for hypertrophic obstructive cardiomyopathy,” at the Royal Brompton Hospital in London in June 1994, with the subsequent description of the first 3 cases in the Lancet in 1995.4 It is of note that the publication of the first 3 ASA cases was immediately followed by a letter to the editor describing ASA as “an uncontrolled manoeuvre on the totality of left ventricular function leading to further left ventricular failure.”9 Interestingly, Sigwart’s brilliant reply contained a statement that “diminishing the outflow tract gradient in patients with symptoms may greatly improve quality of life and reduce symptoms. There is not the slightest evidence that this procedure will lead to acceleration of left ventricular failure.”10 Two decades after this reply, we can state that this controversy heralded the very complicated acceptance of ASA by part of the cardiosurgical society. However, based on the increasing body of evidence demonstrating not only symptomatic improvement after ASA but also survival that was comparable to the general population,11-13 one can also admire Sigwart’s foresight.10 Historical names of ASA underlined the nonsurgical and percutaneous nature of this catheter-based procedure.4,5,11-19 Therefore, several rather descriptive names occurred in the literature, including “nonsurgical septal reduction therapy,”4,18 “percutaneous transluminal septal myocardial ablation,”13,19 and “transcoronary ablation of septal hypertrophy.”5,15,16 The mostly used current designation “alcohol septal ablation” reflects the intraprocedural use of both alcohol and ablation. However, it might be rather confusing that the abbreviation “ASA” is also used for acetylsalicylic acid and Adams-Stokes attack. Technical Aspects In the short history of this procedure, its technique has been repeatedly modified. In the very first years after the introduction of ASA, there was an ongoing discussion about the optimal approach to the selection of the appropriate septal branch for ablation. Primarily, selection was based on an immediate decrease of the LV pressure gradient after the septal branch occlusion by inflation of a short balloon catheter in the proximal part of the selected septal artery. This “physiological”
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approach was modified several times, but the main principle remained the same.4,6,8,15,16 Recently, it was demonstrated that time to significant gradient reduction (> 50%) after septal balloon occlusion predicts the magnitude of final gradient response.17 Soon after the introduction of a physiological approach, several groups of researchers in both Europe and North America demonstrated that the injection of echocardiographic contrast medium into the septal branch is followed by opacification of the septal branch perfusion area.18,19 Proponents of this approach have emphasized that echocardiographybased ASA can easily exclude all patients with the risk of alcohol-induced necrosis remote from the basal septal region. Therefore, this technique was globally accepted and then further improved using Doppler echocardiography with a lower mechanical index designed for myocardial contrast echocardiography (Fig. 1).20 Because some authors warned against the potential longterm malignant consequences of the resultant myocardial scar,21,22 several research groups tried to determine the optimal dose of alcohol associated with sufficient hemodynamic and clinical effect as well as a low incidence of complications.23-26 Initially, higher doses of alcohol were used (3-6 mL). However, in the past decade, data from a long-term randomized study, as well as from registries, showed that a small dose of alcohol (1-2 mL) is sufficient to ensure postprocedural symptomatic relief in about 90% of patients.23-26 Although the use of ASA is possible in > 90% of intended patients, different alternative techniques for catheter-based septal reduction have been used. Initial hemodynamic success followed by ultimate failure resulting from collateral formation was demonstrated with the use of a covered stent implanted into the proximal part of the left anterior descending artery for occlusion of the septal branch.27 Septal ablation using polyvinyl alcohol foam particles resulted in a significant decrease of LV obstruction, but convincing advantages over ASA have never been demonstrated.28 “Glue septal ablation” using cyanoacrylate has also been described.29 However, it is likely that only 3 other techniques might be justified for use in a minority of patients. Reduction of septal thickness using occlusion of the septal branch by coils might be an option in patients with septal collaterals prohibiting the use of alcohol30; similarly, embolization of the septal branch using Embozene microspheres (CeloNova, San Antonio, TX) could decrease the incidence of post-procedural complete heart block as has been demonstrated recently.31 Also, endocardial radiofrequency ablation is justified in patients with (1) small inappropriate septal branches, (2) an a priori conduction abnormality, or (3) after unsuccessful previous myectomy or ASA.32,33 Although all these techniques have been introduced as feasible, safe, and effective, the small number of patients treated does not allow generalization of the first described experience; therefore, these methods should still be considered more or less experimental. Efficacy and Safety The first 3 patients treated by Sigwart et al. reported striking improvements of their symptoms even on the first day after treatment.4 Similarly, authors in both North America and Europe gradually published good short- and long-term
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Canadian Journal of Cardiology Volume 30 2014
Figure 1. During the procedure, contrast myocardial echocardiography is performed to delineate the area to be infarcted and to exclude alcohol injection in remote myocardial regions. The optimal septal branch is identified by opacification of the area in the basal septum, which is adjacent to the zone of maximal acceleration of the outflow jet. Conventional transthoracic imaging (A) and real-time myocardial contrast echocardiography (B, C) with very low mechanical index for intraprocedural visualization of target septal area are used during alcohol septal ablation (ASA).
outcomes in patients undergoing ASA.6,11-20,23-26,34,35 It has been shown that the rapid post-procedural pressure gradient decrease is caused mainly by stunning and myocardial necrosis. The main mechanism of later continuous pressure gradient relief after ASA is the remodelling (widening) of the LV outflow tract developing secondary to infarction and fibrosis of the basal septum.36 Consequently, the basal septal shrinking (Fig. 2) is followed by a gradual reduction in LV mass within the first post-procedural year,37 improvement of diastolic function, and reduction of the degree of mitral regurgitation.38 LV remodelling lasts 6-12 months and seems to be faster in older patients who have a milder degree of LV hypertrophy than in younger patients.39 ASA performed in high-volume centres results in marked clinical improvement in about 90% of patients, with a mean New York Heart Association functional class reduction by 1.5 classes.38 Similarly, a reduction in angina and the incidence of syncope have been also reported.38 This marked clinical improvement is
pathophysiologically based on the significant and durable LV pressure gradient reduction (Fig. 3). All these short-term and midterm results have been derived mainly from relatively large single-centre and multicentre studies or national registries, with the highest number of patients included in the North American Registry (n ¼ 874).40 A major concern associated with ASA was the potentially increased risk of ventricular arrhythmias and sudden cardiac death in the long term. Therefore, most attention was paid to the long-term outcomes and survival after ASA. It took more than 15 years after the first procedure to collect convincing data from registries about acceptable long-term results and the survival of patients after ASA. Several centres showed that the annual all-cause mortality after ASA ranges between 1% and 3%, which is mainly affected by the age and preprocedural patient selection regarding comorbidities.11-17,26,35,38,40,41 However, 2 studies with long-term follow-up demonstrated a similar prognosis in patients who had undergone ASA and
Josef Veselka Alcohol Septal Ablation
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reported in the first decade after the introduction of ASA to be up to 50%, with a mean value of about 30%.38,41 A recent trial by the European Multinational Registry found that in patients without previous conduction abnormalities treated by low-dose ASA, the incidence of mainly transient postprocedural complete heart block was 17%, but only 8% of all patients undergoing ASA needed implantation of a permanent pacemaker before hospital discharge.43 The fact that 97% of all clinical events associated with complete heart block occurred until the fifth post-procedural day is also very important, because this suggests how long the planned hospital stay should be after ASA.43
Figure 2. Post-procedural scarring and shrinkage of the basal septum.
the sex- and age-matched general population.11,12 Additionally, in the Mayo Clinic study, the prognosis of patients after ASA and myectomy was similar.11 Thus, although there is only limited evidence about the long-term survival of patients after ASA, all the studies presented are consistent in the low incidence of sudden death after ASA and a prognosis similar to that in the age- and sex-matched general population. In a meta-analysis of studies performed in the first decade after the introduction of ASA, the procedure-related mortality was about 1.5%, ranging from 0%-5%.38,41 Recently, the North American registry and the European multicentre and multinational registries have shown that early ASA-related mortality in experienced centres is about 0.7%,40,42 and the incidence of ASA-related major adverse clinical events (death, resuscitation, and electrical cardioversion for tachyarrhythmias) is 2.8%.42 However, further complications are not negligible and include complete heart block, which was
Alcohol Septal Ablation vs Myectomy Since the introduction of ASA, the need for a comparison of the efficacy and safety of ASA vs myectomy has been repeatedly discussed.9,10 Although the residual gradient after ASA is still mildly higher, it seems to be generally accepted that the clinical efficacy of both methods is similar. However, a randomized controlled trial focusing on the long-term clinical outcome and comparing both therapies head-to-head is out of the question. The main reason is the low incidence of major clinical end points influencing an event-free survival or all-cause mortality, which would require a high number of patients to ensure a proper statistical power of such a study. Therefore, several authors used meta-analyses to find differences in procedure-related efficacy, safety, and outcome in patients after both options of septal reduction therapy.44,45 The results suggested that the improvement in functional class and exercise capacity was similar. However, after adjustment for available baseline characteristics, the incidence of both all-cause death and sudden death were lower in the ASA cohorts.44,46 Conversely, there is a significantly higher rate of complications after ASA (z20%), which is mainly attributed to the occurrence of complete heart block after ASA.44,45 From the clinical point of view, it seems to be important that the introduction of myectomy and ASA programs varies
Figure 3. Pressure gradient between the left ventricle and aorta before (A) and after procedure (B). AO, aorta; LV, left ventricle.
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greatly from country to country, and ASA has become the first-choice therapy in highly symptomatic patients with HOCM in several European countries. In contrast, there are large North American centres with a long tradition in myectomy that have repeatedly presented outstanding surgical results. Therefore, myectomy continues to be the first choice therapy in countries like the United States, Italy, and perhaps the United Kingdom,46 and ACCF/AHA guidelines for the diagnosis and treatment of hypertrophic cardiomyopathy classified surgical myectomy performed in experienced centres as class IIa and ASA as class IIa in poor surgical candidates or class IIb in all others.1 Conversely, the only North American/ European consensus document on HCM classified ASA as an alternative to myectomy.14 Future Directions Notwithstanding recently published studies with acceptable midterm and long-term results in patients undergoing ASA, researchers working in this field should strengthen the evidence regarding (1) clinical long-term outcome with a focus on survival and risk of sudden cardiac death, (2) risk of late worsening of early conduction abnormalities after ASA that require an additional pacemaker implantation, (3) long-term prognosis of young patients treated with ASA (which is in conflict with current ACCF/AHA guidelines), (4) standardization of procedural technique, and (5) selection of optimal patients for ASA, taking into account the LV morphologic characteristics, including papillary muscles and mitral leaflets abnormalities. Based on common sense, one can assume that the optimal approach to “septum reduction therapy” should be individualized for each patient with HOCM. Therefore, further data from centres providing both catheter-based and surgical therapy are badly needed. Conclusions Since the first ASA procedure performed by Sigwart et al. almost 20 years ago,4 ASA has become a widely used technique for the treatment of highly symptomatic patients with HOCM. Interestingly, it took almost 2 decades before the procedure was given due recognition and enough evidence was collected in support of its use. However, we still have to be aware that a knowledge gap exists with regard to long-term outcomes after ASA. Therefore, careful selection of patients for ASA should be performed, and all these patients should be treated in HCM centres offering all therapeutic options. Funding Sources J.V. is supported by the project for conceptual development of research organization 00064203 and Grant NT 11401-5 from the Internal Grant Agency, Ministry of Health, Czech Republic. Disclosures The author has no conflicts of interest to disclose. References 1. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy. Circulation 2011;124:e783-831.
Canadian Journal of Cardiology Volume 30 2014 2. Kirklin JW, Ellis FH Jr. Surgical relief of diffuse subvalvular aortic stenosis. Circulation 1961;24:739-42. 3. Morrow AG, Brockenbrough EC. Surgical treatment of idiopathic hypertrophic subaortic stenosis: technique and hemodynamic results of subaortic ventriculomyotomy. Ann Surg 1961;154:181-9. 4. Sigwart U. Non-surgical myocardial reduction of hypertrophic obstructive cardiomyopathy. Lancet 1995;346:211-4. 5. Kuhn HJ. The history of alcohol septal ablation. Cardiovasc Revasc Med 2010;11:260-1. 6. Kuhn H, Gietzen F, Leuner C, Gerenkamp T. Induction of subaortic septal ischemia to reduce obstruction in hypertrophic obstructive cardiomyopathy. Studies to develop a new catheter-based concept of treatment. Eur Heart J 1997;18:846-51. 7. Brugada P, de Swart H, Smeets JL, Wellens H. Transcoronary chemical ablation of ventricular tachycardia. Circulation 1989;79:475-82. 8. Gietzen F, Leuner C, Gerenkamp T, Kuhn H. Abnahme der Obstruktion bei hypertrophischer Kardiomyopathie wahrend passage Okklusion des ersten Septalastes der linken Koronararterie. Z Kardiol 1994;83(suppl 1):146. 9. Goodwin JF, Oakley CM. Non-surgical myocardial reduction for hypertrophic obstructive cardiomyopathy. Lancet 1995;346:1624. 10. Sigwart U. Author’s reply. Lancet 1995;346:1624. 11. Sorajja P, Ommen SR, Holmes DR Jr, et al. Survival after alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Circulation 2012;16:2374-80. 12. Jensen MK, Prinz C, Horstkotte D, et al. Alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy: low incidence of sudden cardiac death and reduced risk profile. Heart 2013;99:1012-7. 13. Jensen MK, Almaas VM, Jacobsson L, et al. Long-term outcome of percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy. Circ Cardiovasc Interv 2011;4:256-65. 14. Maron BJ, McKenna WJ, Danielson GK, et al. American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic cardiomyopathy. Eur Heart J 2003;24: 1965-91. 15. Gietzen FH, Leuner CJ, Raute-Kreisen U, et al. Acute and long-term results after transcoronary ablation of septal hypertrophy (TASH). Eur Heart J 1999;20:1342-54. 16. 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: 2356-63. 17. Almasood A, Garceau P, Woo A, et al. Time to significant gradient reduction following septal balloon occlusion predicts the magnitude of final gradient response during alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy. JACC Cardiovasc Interv 2011;4:1030-4. 18. Nagueh SF, Lakkis NM, He ZX, et al. Role of myocardial contrast echocardiography during nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 1998;32: 225-9. 19. Faber L, Seggewiss H, Gleichmann U. Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: results with respect to intraprocedural myocardial contrast echocardiography. Circulation 1998;98:2415-21.
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20. Veselka J, Zemánek D, Fiedler J, Sváb P. Real-time myocardial contrast echocardiography for echo-guided alcohol septal ablation. Arch Med Sci 2009;5:271-2.
33. Lawrenz T, Borchert B, Leuner C, et al. Endocardial radiofrequency ablation for hypertrophic obstructive cardiomyopathy: acute results and 6-month follow-up in 19 patients. J Am Coll Cardiol 2001;57:572-6.
21. Efthimiadis GK. Septal alcohol ablation in hypertrophic obstructive cardiomyopathy: improving cardiac function by generating a myocardial scar. Eur Heart J 2007;28:1270-1.
34. Lakkis N, Plana JC, Nagueh S, et al. Efficacy of nonsurgical septal reduction therapy in symptomatic patients with obstructive hypertrophic cardiomyopathy and provocable gradients. Am J Cardiol 2001;88:583-6.
22. Maron BJ. Role of alcohol septal ablation in treatment of obstructive hypertrophic cardiomyopathy. Lancet 2000;355:425-6.
35. 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;5:347-55.
23. Kuhn H, Lawrenz T, Lieder F, et al. Survival after transcoronary ablation of septal hypertrophy in hypertrophic obstructive cardiomyopathy (TASH): a 10 year experience. Clin Res Cardiol 2008;97:234-43. 24. Veselka J, Zemanek D, Tomasov P, Duchonova R, Linhartova K. Alcohol septal ablation for obstructive hypertrophic cardiomyopathy: ultra-low dose of alcohol (1 ml) is still effective. Heart Vessels 2009;24: 27-31. 25. Veselka J, Duchonova R, Prochazkova S, et al. Effects of varying ethanol dosing in percutaneous septal ablation for obstructive hypertrophic cardiomyopathy on early hemodynamic changes. Am J Cardiol 2005;95: 675-8. 26. Veselka J, Tomasov P, Zemánek D. Long-term effects of varying alcohol dosing in percutaneous alcohol septal ablation for hypertrophic obstructive cardiomyopathy: a randomized study with a follow-up up to 11 years. Can J Cardiol 2011;27:763-7. 27. Fifer MA, Yoerger DM, Picard MH, Vlahakes GJ, Palacios IF. Covered stent septal ablation for hypertrophic obstructive cardiomyopathy: initial success but ultimate failure resulting from collateral formation. Circulation 2003;107:3248-9. 28. Gross CM, Schulz-Menger J, Kramer J, et al. Percutaneous transluminal septal artery ablation using polyvinyl alcohol foam particles for septal hypertrophy in patients with hypertrophic obstructive cardiomyopathy: acute and 3-year outcomes. J Endovasc Ther 2004;11:705-11. 29. Oto A, Aytemir K, Deniz A. New approach to septal ablation: glue (cyanoacrylate) septal ablation. Catheter Cardiovasc Interv 2007;69: 1021-5. 30. Durand E, Mousseaux E, Coste P, et al. Non-surgical septal myocardial reduction by coil embolization for hypertrophic obstructive cardiomyopathy: early and 6-month follow-up. Eur Heart J 2008;29:348-55. 31. Latsios G, Gerckens U, Mueller R, Grube E. Substitution of ethanol with specially designed microspheres in a TASH procedure. EuroIntervention 2011;6:889-92. 32. Riedlbauchova L, Janousek J, Veselka J. Ablation of hypertrophic septum using radiofrequency energydan alternative for gradient reduction in patient with hypertrophic obstructive cardiomyopathy? J Invasive Cardiol 2013;25:E128-32.
36. Veselka J, Duchonová R, Procházková S, et al. The biphasic course of changes of left ventricular outflow gradient after alcohol septal ablation for hypertrophic obstructive cardiomyopathy. Kardiol Pol 2004;60: 133-6. 37. Mazur W, Nagueh SF, Lakkis NM, et al. Regression of left ventricular hypertrophy after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy. Circulation 2001;103:1492-6. 38. Fifer MA, Sigwart U. Hypertrophic obstructive cardiomyopathy: alcohol septal ablation. Eur Heart J 2011;32:1059-64. 39. Veselka J, Duchonova R, Palenickova J, et al. Age-related hemodynamic and morphologic differences in patients undergoing alcohol septal ablation for hypertrophic obstructive cardiomyopathy. Circ J 2006;70:880-4. 40. Nagueh SF, Groves BM, Schwartz L, et al. Alcohol septal ablation for the treatment of hypertrophic obstructive cardiomyopathy: a Multicenter North American registry. J Am Coll Cardiol 2011;58:2322-8. 41. Alam M, Dokainish H, Lakkis NM. Alcohol septal ablation for hypertrophic obstructive cardiomyopathy. A systematic review of literature. J Intervent Cardiol 2006;19:319-27. 42. Veselka J, Lawrenz T, Stellbrink C, et al. Early outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy: a European multicenter and multinational study. Catheter Cardiovasc Interv 2013. [Epub ahead of print] 43. Veselka J, Lawrenz T, Stellbrink C, et al. Low incidence of procedurerelated major adverse cardiac events following alcohol septal ablation for symptomatic hypertrophic obstructive cardiomyopathy. Can J Cardiol 2013;29:1415-21. 44. Leonardi RA, Kransdorf EP, Simel DL, Wang A. Meta-analyses of septal reduction therapies for obstructive hypertrophic cardiomyopathy: comparative rates of overall mortality and sudden cardiac death after treatment. Circulation Cardiovasc Interv 2010;3:97-104. 45. Agarwal S, Tuzcu EM, Desai MY, et al. Updated meta-analysis of septal alcohol ablation versus myectomy for hypertrophic cardiomyopathy. J Am Coll Cardiol 2010;55:823-34. 46. Gimeno JR, Tome MT, McKenna WJ. Alcohol septal ablation in hypertrophic cardiomyopathy: an opportunity to be taken. Rev Esp Cardiol 2012;65:314-8.
Review
Historical Milestones and Progress in the Research on Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy Josef Veselka, MD, PhD Department of Cardiology, 2nd Medical School, Charles University and University Hospital Motol, Prague, Czech Republic
ABSTRACT
RESUM E
The first alcohol septal ablation was performed almost 20 years ago in 1994; since then it has become a widely used technique for the treatment of highly symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). It has been shown that postprocedural basal septal shrinking as a result of myocardial scarring is followed by a decrease in left ventricular (LV) obstruction, regression of LV hypertrophy within the first postprocedural year, improvement of diastolic function, and reduction of the degree of mitral regurgitation. All these changes are accompanied by significant symptom relief. Although there is only limited evidence of postprocedural long-term survival, all the studies presented here are consistent in the low incidence of sudden death and similar prognoses with an age- and sex-matched general population. Conversely, we still have to be aware that a certain knowledge gap exists with regard to postprocedural longterm outcome. Therefore, careful selection of patients for alcohol septal ablation is needed, and all patients should be treated in centres offering all therapeutic options.
te re alise e il y a presque 20 La première ablation septale à l’alcool a e e dans le ans, en 1994. Depuis, elle est une technique très utilise traitement des patients fortement symptomatiques ayant une car te de montre diomyopathie hypertrophique obstructive (CMHO). Il a e tre cissement postinterventionnel du septum basal à la suite que le re de la cicatrisation du myocarde est suivi d’une diminution de l’obgression de l’hypertrophie struction du ventricule gauche, de la re e après l’intervenventriculaire gauche au cours de la première anne lioration du fonctionnement diastolique et de la tion, de l’ame duction du degre de la re gurgitation mitrale. Tous ces changements re s d’un soulagement significatif des symptômes. Bien sont accompagne es scientifiques sur la survie à long qu’il n’existe que peu de donne tudes publie es confirment la terme après l’intervention, toutes les e quence de mort subite et de pronostics similaires sur une faible fre ne rale apparie e selon l’âge et le sexe. En contrepartie, population ge nous devons demeurer conscients du fait qu’il existe un certain manvolution à long terme après que de connaissance en ce qui concerne l’e lection rigoureuse des patients qui subiront l’intervention. Ainsi, une se cessaire, et tous les patients del’ablation septale à l’alcool est ne s dans des centres offrant toutes les options vraient être traite rapeutiques. the
Historical Introduction Hypertrophic cardiomyopathy (HCM) is characterized by unexplained hypertrophy of the left (or also right) ventricle in the absence of another disease that would be capable of producing the magnitude of hypertrophy in a given patient and is mostly caused by an autosomal dominant mutation in genes encoding sarcomere or sarcomere-associated proteins.1 Approximately two thirds of patients have significant left ventricular (LV) obstruction at rest ( 30 mm Hg) or at physiologic provocation ( 50 mm Hg).1 Outflow obstruc
tion is responsible for increased LV systolic pressure, which consequently leads to myocardial ischemia, mitral regurgitation, and impairment of diastolic and systolic function. All this eventually leads to pulmonary hypertension and congestive heart failure. Therefore, highly symptomatic patients who have a large LV gradient and do not respond to medical therapy have been considered the best candidates for surgical myectomy. In the early 1960s, several surgical centres began performing septal myectomy with the removal of a small amount of muscle (5 to 10 g) from the basal septum2,3 Also, mitral valve replacement was used as an alternative therapy in selected patients to eliminate subaortic obstruction, but it is not an acceptable therapeutic approach now. According to the only American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guideline for the diagnosis and treatment of HCM, surgical myectomy is still the “firstoption” and “gold standard” therapy of hypertrophic obstructive cardiomyopathy (HOCM).1
Received for publication September 15, 2013. Accepted October 1, 2013. Corresponding author: Dr Josef Veselka, Department of Cardiology, V úvalu 84, Prague 5, 15000, Czech Republic. Tel.: þ420224434900; fax: þ420224434920. E-mail: [email protected] See page 50 for disclosure information.
0828-282X/$ - see front matter Ó 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cjca.2013.10.001
Josef Veselka Alcohol Septal Ablation
The development of interventional cardiology in the 1980s and 1990s of the past century led to attempts to eliminate LV obstruction by catheter-based techniques, consequently decreasing the morbidity and mortality of HOCM. The idea of inducing septal infarction by catheter techniques was primarily suggested by the observation that myocardial function of selected areas of the left ventricle can be suppressed by balloon occlusion of the supplying artery during angioplasty. The outflow gradient in HOCM decreased significantly when the first septal artery was temporarily occluded by an angioplasty balloon catheter.4-6 The suggestion to use alcohol for permanent ablation of a hypertrophic septum was likely derived from Brugada et al.’s work dealing with the treatment of ventricular arrhythmias by intracoronary alcohol injection.7 At least 2 groups of researchers, almost at the same time, progressed rapidly to alcohol ablation for HOCM. Gietzen et al. presented their preliminary results at the Annual Congress of the German Cardiac Society in April 1994,8 and Sigwart et al. performed the first alcohol septal ablation (ASA), which was called at that time “nonsurgical myocardial reduction for hypertrophic obstructive cardiomyopathy,” at the Royal Brompton Hospital in London in June 1994, with the subsequent description of the first 3 cases in the Lancet in 1995.4 It is of note that the publication of the first 3 ASA cases was immediately followed by a letter to the editor describing ASA as “an uncontrolled manoeuvre on the totality of left ventricular function leading to further left ventricular failure.”9 Interestingly, Sigwart’s brilliant reply contained a statement that “diminishing the outflow tract gradient in patients with symptoms may greatly improve quality of life and reduce symptoms. There is not the slightest evidence that this procedure will lead to acceleration of left ventricular failure.”10 Two decades after this reply, we can state that this controversy heralded the very complicated acceptance of ASA by part of the cardiosurgical society. However, based on the increasing body of evidence demonstrating not only symptomatic improvement after ASA but also survival that was comparable to the general population,11-13 one can also admire Sigwart’s foresight.10 Historical names of ASA underlined the nonsurgical and percutaneous nature of this catheter-based procedure.4,5,11-19 Therefore, several rather descriptive names occurred in the literature, including “nonsurgical septal reduction therapy,”4,18 “percutaneous transluminal septal myocardial ablation,”13,19 and “transcoronary ablation of septal hypertrophy.”5,15,16 The mostly used current designation “alcohol septal ablation” reflects the intraprocedural use of both alcohol and ablation. However, it might be rather confusing that the abbreviation “ASA” is also used for acetylsalicylic acid and Adams-Stokes attack. Technical Aspects In the short history of this procedure, its technique has been repeatedly modified. In the very first years after the introduction of ASA, there was an ongoing discussion about the optimal approach to the selection of the appropriate septal branch for ablation. Primarily, selection was based on an immediate decrease of the LV pressure gradient after the septal branch occlusion by inflation of a short balloon catheter in the proximal part of the selected septal artery. This “physiological”
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approach was modified several times, but the main principle remained the same.4,6,8,15,16 Recently, it was demonstrated that time to significant gradient reduction (> 50%) after septal balloon occlusion predicts the magnitude of final gradient response.17 Soon after the introduction of a physiological approach, several groups of researchers in both Europe and North America demonstrated that the injection of echocardiographic contrast medium into the septal branch is followed by opacification of the septal branch perfusion area.18,19 Proponents of this approach have emphasized that echocardiographybased ASA can easily exclude all patients with the risk of alcohol-induced necrosis remote from the basal septal region. Therefore, this technique was globally accepted and then further improved using Doppler echocardiography with a lower mechanical index designed for myocardial contrast echocardiography (Fig. 1).20 Because some authors warned against the potential longterm malignant consequences of the resultant myocardial scar,21,22 several research groups tried to determine the optimal dose of alcohol associated with sufficient hemodynamic and clinical effect as well as a low incidence of complications.23-26 Initially, higher doses of alcohol were used (3-6 mL). However, in the past decade, data from a long-term randomized study, as well as from registries, showed that a small dose of alcohol (1-2 mL) is sufficient to ensure postprocedural symptomatic relief in about 90% of patients.23-26 Although the use of ASA is possible in > 90% of intended patients, different alternative techniques for catheter-based septal reduction have been used. Initial hemodynamic success followed by ultimate failure resulting from collateral formation was demonstrated with the use of a covered stent implanted into the proximal part of the left anterior descending artery for occlusion of the septal branch.27 Septal ablation using polyvinyl alcohol foam particles resulted in a significant decrease of LV obstruction, but convincing advantages over ASA have never been demonstrated.28 “Glue septal ablation” using cyanoacrylate has also been described.29 However, it is likely that only 3 other techniques might be justified for use in a minority of patients. Reduction of septal thickness using occlusion of the septal branch by coils might be an option in patients with septal collaterals prohibiting the use of alcohol30; similarly, embolization of the septal branch using Embozene microspheres (CeloNova, San Antonio, TX) could decrease the incidence of post-procedural complete heart block as has been demonstrated recently.31 Also, endocardial radiofrequency ablation is justified in patients with (1) small inappropriate septal branches, (2) an a priori conduction abnormality, or (3) after unsuccessful previous myectomy or ASA.32,33 Although all these techniques have been introduced as feasible, safe, and effective, the small number of patients treated does not allow generalization of the first described experience; therefore, these methods should still be considered more or less experimental. Efficacy and Safety The first 3 patients treated by Sigwart et al. reported striking improvements of their symptoms even on the first day after treatment.4 Similarly, authors in both North America and Europe gradually published good short- and long-term
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Canadian Journal of Cardiology Volume 30 2014
Figure 1. During the procedure, contrast myocardial echocardiography is performed to delineate the area to be infarcted and to exclude alcohol injection in remote myocardial regions. The optimal septal branch is identified by opacification of the area in the basal septum, which is adjacent to the zone of maximal acceleration of the outflow jet. Conventional transthoracic imaging (A) and real-time myocardial contrast echocardiography (B, C) with very low mechanical index for intraprocedural visualization of target septal area are used during alcohol septal ablation (ASA).
outcomes in patients undergoing ASA.6,11-20,23-26,34,35 It has been shown that the rapid post-procedural pressure gradient decrease is caused mainly by stunning and myocardial necrosis. The main mechanism of later continuous pressure gradient relief after ASA is the remodelling (widening) of the LV outflow tract developing secondary to infarction and fibrosis of the basal septum.36 Consequently, the basal septal shrinking (Fig. 2) is followed by a gradual reduction in LV mass within the first post-procedural year,37 improvement of diastolic function, and reduction of the degree of mitral regurgitation.38 LV remodelling lasts 6-12 months and seems to be faster in older patients who have a milder degree of LV hypertrophy than in younger patients.39 ASA performed in high-volume centres results in marked clinical improvement in about 90% of patients, with a mean New York Heart Association functional class reduction by 1.5 classes.38 Similarly, a reduction in angina and the incidence of syncope have been also reported.38 This marked clinical improvement is
pathophysiologically based on the significant and durable LV pressure gradient reduction (Fig. 3). All these short-term and midterm results have been derived mainly from relatively large single-centre and multicentre studies or national registries, with the highest number of patients included in the North American Registry (n ¼ 874).40 A major concern associated with ASA was the potentially increased risk of ventricular arrhythmias and sudden cardiac death in the long term. Therefore, most attention was paid to the long-term outcomes and survival after ASA. It took more than 15 years after the first procedure to collect convincing data from registries about acceptable long-term results and the survival of patients after ASA. Several centres showed that the annual all-cause mortality after ASA ranges between 1% and 3%, which is mainly affected by the age and preprocedural patient selection regarding comorbidities.11-17,26,35,38,40,41 However, 2 studies with long-term follow-up demonstrated a similar prognosis in patients who had undergone ASA and
Josef Veselka Alcohol Septal Ablation
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reported in the first decade after the introduction of ASA to be up to 50%, with a mean value of about 30%.38,41 A recent trial by the European Multinational Registry found that in patients without previous conduction abnormalities treated by low-dose ASA, the incidence of mainly transient postprocedural complete heart block was 17%, but only 8% of all patients undergoing ASA needed implantation of a permanent pacemaker before hospital discharge.43 The fact that 97% of all clinical events associated with complete heart block occurred until the fifth post-procedural day is also very important, because this suggests how long the planned hospital stay should be after ASA.43
Figure 2. Post-procedural scarring and shrinkage of the basal septum.
the sex- and age-matched general population.11,12 Additionally, in the Mayo Clinic study, the prognosis of patients after ASA and myectomy was similar.11 Thus, although there is only limited evidence about the long-term survival of patients after ASA, all the studies presented are consistent in the low incidence of sudden death after ASA and a prognosis similar to that in the age- and sex-matched general population. In a meta-analysis of studies performed in the first decade after the introduction of ASA, the procedure-related mortality was about 1.5%, ranging from 0%-5%.38,41 Recently, the North American registry and the European multicentre and multinational registries have shown that early ASA-related mortality in experienced centres is about 0.7%,40,42 and the incidence of ASA-related major adverse clinical events (death, resuscitation, and electrical cardioversion for tachyarrhythmias) is 2.8%.42 However, further complications are not negligible and include complete heart block, which was
Alcohol Septal Ablation vs Myectomy Since the introduction of ASA, the need for a comparison of the efficacy and safety of ASA vs myectomy has been repeatedly discussed.9,10 Although the residual gradient after ASA is still mildly higher, it seems to be generally accepted that the clinical efficacy of both methods is similar. However, a randomized controlled trial focusing on the long-term clinical outcome and comparing both therapies head-to-head is out of the question. The main reason is the low incidence of major clinical end points influencing an event-free survival or all-cause mortality, which would require a high number of patients to ensure a proper statistical power of such a study. Therefore, several authors used meta-analyses to find differences in procedure-related efficacy, safety, and outcome in patients after both options of septal reduction therapy.44,45 The results suggested that the improvement in functional class and exercise capacity was similar. However, after adjustment for available baseline characteristics, the incidence of both all-cause death and sudden death were lower in the ASA cohorts.44,46 Conversely, there is a significantly higher rate of complications after ASA (z20%), which is mainly attributed to the occurrence of complete heart block after ASA.44,45 From the clinical point of view, it seems to be important that the introduction of myectomy and ASA programs varies
Figure 3. Pressure gradient between the left ventricle and aorta before (A) and after procedure (B). AO, aorta; LV, left ventricle.
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greatly from country to country, and ASA has become the first-choice therapy in highly symptomatic patients with HOCM in several European countries. In contrast, there are large North American centres with a long tradition in myectomy that have repeatedly presented outstanding surgical results. Therefore, myectomy continues to be the first choice therapy in countries like the United States, Italy, and perhaps the United Kingdom,46 and ACCF/AHA guidelines for the diagnosis and treatment of hypertrophic cardiomyopathy classified surgical myectomy performed in experienced centres as class IIa and ASA as class IIa in poor surgical candidates or class IIb in all others.1 Conversely, the only North American/ European consensus document on HCM classified ASA as an alternative to myectomy.14 Future Directions Notwithstanding recently published studies with acceptable midterm and long-term results in patients undergoing ASA, researchers working in this field should strengthen the evidence regarding (1) clinical long-term outcome with a focus on survival and risk of sudden cardiac death, (2) risk of late worsening of early conduction abnormalities after ASA that require an additional pacemaker implantation, (3) long-term prognosis of young patients treated with ASA (which is in conflict with current ACCF/AHA guidelines), (4) standardization of procedural technique, and (5) selection of optimal patients for ASA, taking into account the LV morphologic characteristics, including papillary muscles and mitral leaflets abnormalities. Based on common sense, one can assume that the optimal approach to “septum reduction therapy” should be individualized for each patient with HOCM. Therefore, further data from centres providing both catheter-based and surgical therapy are badly needed. Conclusions Since the first ASA procedure performed by Sigwart et al. almost 20 years ago,4 ASA has become a widely used technique for the treatment of highly symptomatic patients with HOCM. Interestingly, it took almost 2 decades before the procedure was given due recognition and enough evidence was collected in support of its use. However, we still have to be aware that a knowledge gap exists with regard to long-term outcomes after ASA. Therefore, careful selection of patients for ASA should be performed, and all these patients should be treated in HCM centres offering all therapeutic options. Funding Sources J.V. is supported by the project for conceptual development of research organization 00064203 and Grant NT 11401-5 from the Internal Grant Agency, Ministry of Health, Czech Republic. Disclosures The author has no conflicts of interest to disclose. References 1. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy. Circulation 2011;124:e783-831.
Canadian Journal of Cardiology Volume 30 2014 2. Kirklin JW, Ellis FH Jr. Surgical relief of diffuse subvalvular aortic stenosis. Circulation 1961;24:739-42. 3. Morrow AG, Brockenbrough EC. Surgical treatment of idiopathic hypertrophic subaortic stenosis: technique and hemodynamic results of subaortic ventriculomyotomy. Ann Surg 1961;154:181-9. 4. Sigwart U. Non-surgical myocardial reduction of hypertrophic obstructive cardiomyopathy. Lancet 1995;346:211-4. 5. Kuhn HJ. The history of alcohol septal ablation. Cardiovasc Revasc Med 2010;11:260-1. 6. Kuhn H, Gietzen F, Leuner C, Gerenkamp T. Induction of subaortic septal ischemia to reduce obstruction in hypertrophic obstructive cardiomyopathy. Studies to develop a new catheter-based concept of treatment. Eur Heart J 1997;18:846-51. 7. Brugada P, de Swart H, Smeets JL, Wellens H. Transcoronary chemical ablation of ventricular tachycardia. Circulation 1989;79:475-82. 8. Gietzen F, Leuner C, Gerenkamp T, Kuhn H. Abnahme der Obstruktion bei hypertrophischer Kardiomyopathie wahrend passage Okklusion des ersten Septalastes der linken Koronararterie. Z Kardiol 1994;83(suppl 1):146. 9. Goodwin JF, Oakley CM. Non-surgical myocardial reduction for hypertrophic obstructive cardiomyopathy. Lancet 1995;346:1624. 10. Sigwart U. Author’s reply. Lancet 1995;346:1624. 11. Sorajja P, Ommen SR, Holmes DR Jr, et al. Survival after alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Circulation 2012;16:2374-80. 12. Jensen MK, Prinz C, Horstkotte D, et al. Alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy: low incidence of sudden cardiac death and reduced risk profile. Heart 2013;99:1012-7. 13. Jensen MK, Almaas VM, Jacobsson L, et al. Long-term outcome of percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy. Circ Cardiovasc Interv 2011;4:256-65. 14. Maron BJ, McKenna WJ, Danielson GK, et al. American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic cardiomyopathy. Eur Heart J 2003;24: 1965-91. 15. Gietzen FH, Leuner CJ, Raute-Kreisen U, et al. Acute and long-term results after transcoronary ablation of septal hypertrophy (TASH). Eur Heart J 1999;20:1342-54. 16. 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: 2356-63. 17. Almasood A, Garceau P, Woo A, et al. Time to significant gradient reduction following septal balloon occlusion predicts the magnitude of final gradient response during alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy. JACC Cardiovasc Interv 2011;4:1030-4. 18. Nagueh SF, Lakkis NM, He ZX, et al. Role of myocardial contrast echocardiography during nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol 1998;32: 225-9. 19. Faber L, Seggewiss H, Gleichmann U. Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: results with respect to intraprocedural myocardial contrast echocardiography. Circulation 1998;98:2415-21.
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20. Veselka J, Zemánek D, Fiedler J, Sváb P. Real-time myocardial contrast echocardiography for echo-guided alcohol septal ablation. Arch Med Sci 2009;5:271-2.
33. Lawrenz T, Borchert B, Leuner C, et al. Endocardial radiofrequency ablation for hypertrophic obstructive cardiomyopathy: acute results and 6-month follow-up in 19 patients. J Am Coll Cardiol 2001;57:572-6.
21. Efthimiadis GK. Septal alcohol ablation in hypertrophic obstructive cardiomyopathy: improving cardiac function by generating a myocardial scar. Eur Heart J 2007;28:1270-1.
34. Lakkis N, Plana JC, Nagueh S, et al. Efficacy of nonsurgical septal reduction therapy in symptomatic patients with obstructive hypertrophic cardiomyopathy and provocable gradients. Am J Cardiol 2001;88:583-6.
22. Maron BJ. Role of alcohol septal ablation in treatment of obstructive hypertrophic cardiomyopathy. Lancet 2000;355:425-6.
35. 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;5:347-55.
23. Kuhn H, Lawrenz T, Lieder F, et al. Survival after transcoronary ablation of septal hypertrophy in hypertrophic obstructive cardiomyopathy (TASH): a 10 year experience. Clin Res Cardiol 2008;97:234-43. 24. Veselka J, Zemanek D, Tomasov P, Duchonova R, Linhartova K. Alcohol septal ablation for obstructive hypertrophic cardiomyopathy: ultra-low dose of alcohol (1 ml) is still effective. Heart Vessels 2009;24: 27-31. 25. Veselka J, Duchonova R, Prochazkova S, et al. Effects of varying ethanol dosing in percutaneous septal ablation for obstructive hypertrophic cardiomyopathy on early hemodynamic changes. Am J Cardiol 2005;95: 675-8. 26. Veselka J, Tomasov P, Zemánek D. Long-term effects of varying alcohol dosing in percutaneous alcohol septal ablation for hypertrophic obstructive cardiomyopathy: a randomized study with a follow-up up to 11 years. Can J Cardiol 2011;27:763-7. 27. Fifer MA, Yoerger DM, Picard MH, Vlahakes GJ, Palacios IF. Covered stent septal ablation for hypertrophic obstructive cardiomyopathy: initial success but ultimate failure resulting from collateral formation. Circulation 2003;107:3248-9. 28. Gross CM, Schulz-Menger J, Kramer J, et al. Percutaneous transluminal septal artery ablation using polyvinyl alcohol foam particles for septal hypertrophy in patients with hypertrophic obstructive cardiomyopathy: acute and 3-year outcomes. J Endovasc Ther 2004;11:705-11. 29. Oto A, Aytemir K, Deniz A. New approach to septal ablation: glue (cyanoacrylate) septal ablation. Catheter Cardiovasc Interv 2007;69: 1021-5. 30. Durand E, Mousseaux E, Coste P, et al. Non-surgical septal myocardial reduction by coil embolization for hypertrophic obstructive cardiomyopathy: early and 6-month follow-up. Eur Heart J 2008;29:348-55. 31. Latsios G, Gerckens U, Mueller R, Grube E. Substitution of ethanol with specially designed microspheres in a TASH procedure. EuroIntervention 2011;6:889-92. 32. Riedlbauchova L, Janousek J, Veselka J. Ablation of hypertrophic septum using radiofrequency energydan alternative for gradient reduction in patient with hypertrophic obstructive cardiomyopathy? J Invasive Cardiol 2013;25:E128-32.
36. Veselka J, Duchonová R, Procházková S, et al. The biphasic course of changes of left ventricular outflow gradient after alcohol septal ablation for hypertrophic obstructive cardiomyopathy. Kardiol Pol 2004;60: 133-6. 37. Mazur W, Nagueh SF, Lakkis NM, et al. Regression of left ventricular hypertrophy after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy. Circulation 2001;103:1492-6. 38. Fifer MA, Sigwart U. Hypertrophic obstructive cardiomyopathy: alcohol septal ablation. Eur Heart J 2011;32:1059-64. 39. Veselka J, Duchonova R, Palenickova J, et al. Age-related hemodynamic and morphologic differences in patients undergoing alcohol septal ablation for hypertrophic obstructive cardiomyopathy. Circ J 2006;70:880-4. 40. Nagueh SF, Groves BM, Schwartz L, et al. Alcohol septal ablation for the treatment of hypertrophic obstructive cardiomyopathy: a Multicenter North American registry. J Am Coll Cardiol 2011;58:2322-8. 41. Alam M, Dokainish H, Lakkis NM. Alcohol septal ablation for hypertrophic obstructive cardiomyopathy. A systematic review of literature. J Intervent Cardiol 2006;19:319-27. 42. Veselka J, Lawrenz T, Stellbrink C, et al. Early outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy: a European multicenter and multinational study. Catheter Cardiovasc Interv 2013. [Epub ahead of print] 43. Veselka J, Lawrenz T, Stellbrink C, et al. Low incidence of procedurerelated major adverse cardiac events following alcohol septal ablation for symptomatic hypertrophic obstructive cardiomyopathy. Can J Cardiol 2013;29:1415-21. 44. Leonardi RA, Kransdorf EP, Simel DL, Wang A. Meta-analyses of septal reduction therapies for obstructive hypertrophic cardiomyopathy: comparative rates of overall mortality and sudden cardiac death after treatment. Circulation Cardiovasc Interv 2010;3:97-104. 45. Agarwal S, Tuzcu EM, Desai MY, et al. Updated meta-analysis of septal alcohol ablation versus myectomy for hypertrophic cardiomyopathy. J Am Coll Cardiol 2010;55:823-34. 46. Gimeno JR, Tome MT, McKenna WJ. Alcohol septal ablation in hypertrophic cardiomyopathy: an opportunity to be taken. Rev Esp Cardiol 2012;65:314-8.