Abstract: Hypertrophic cardiomyopathy is the most common genetically transmitted heart disease. Around two-thirds of patients develop symptoms caused by the dynamic left ventricular outflow tract obstruction, either at rest or during effort. For patients with hypertrophic obstructive cardiomyopathy (HOCM) that remain symptomatic despite optimal medical treatment, septal reduction is a valuable therapeutic strategy. While surgical myomectomy was considered the gold standard until the end of the 1990s, alcohol septal ablation (ASA) has gained rapid popularity and acceptance, especially in Europe. In this review, we describe indications and contraindications to ASA, along with technical considerations related to the procedure. Particular emphasis is put on adjunctive imaging modalities required for proper patient selection (echocardiography, magnetic resonance imaging) and procedure safety (echocardiography). Next, we describe postprocedural care and potential procedural complications. Finally, a review of the recent literature describing the long-term results of ASA is presented. In short, when performed by an experienced team, ASA has a high success rate and low complication rate. The procedure provides symptom relief and grants patients similar longevity to that of the general population.
J INVASIVE CARDIOL 2017;29(12):404-410.
Key words: alcohol septal ablation, hypertrophic obstructive cardiomyopathy, radial access
Hypertrophic Cardiomyopathy: An Overview
Hypertrophic cardiomyopathy (HCM) affects 1 out of 500 individuals in the general population and may be more prevalent in men than women, although the gender difference in prevalence has not been confirmed.1 It is the most common genetic cardiac condition and is inherited as an autosomal-dominant trait with variable penetrance. Several mutations have been described, but in most cases the gene involved encodes a cardiac sarcomere protein. Variable phenotypic penetrance and unclear symptoms may sometimes result in the diagnosis being established once the affected individuals have reached adulthood, with potentially severe myocardial dysfunction at the time of presentation. Patients may present with symptoms ranging from mild fatigue to severe congestive or non-congestive heart failure, syncope, or angina.
The diagnosis of hypertrophic obstructive cardiomyopathy (HOCM) is based on the presence of a dynamic intracavitary gradient. The obstruction is described as dynamic because it varies depending on various physiological factors (exertion, relative hypervolemia/hypovolemia, ventricular extrasystole, Valsalva maneuver). Cardiac magnetic resonance imaging enables the accurate delineation of the mitral valve apparatus, localization and assessment of the degree of left ventricular hypertrophy, as well as the extent and distribution of myocardial fibrosis, which appears to have an impact on outcomes. Late gadolinium enhancement on cardiac magnetic resonance may be associated with sudden death, ventricular tachycardia, and the risk of burnt-out disease over time, but these links are still being determined. Approximately one-third of patients with HCM have a physiological pattern of obstruction at rest worsened with exertion, one-third solely during exertion, and one-third have non-obstructive HCM. The latter group of patients is usually managed medically only. Rarely, they may require interventions such as transplantation in the case of severe ventricular dysfunction or intractable ventricular arrhythmia. Patients with physiological obstruction are treated with combined invasive and pharmacological therapeutic modalities.
Therapeutic options. Treatment objectives in HOCM are to relieve symptoms and reduce the risks of syncope or sudden death. Overall, there are four therapeutic modalities. The first is recommended for all patients and involves lifestyle changes: avoidance of high-level competitive sports, dehydration, alcohol, caffeine, and cocaine. Other therapeutic options include pharmacologic management, dual-chamber pacemaker implantation, and septal reduction strategies (surgical myomectomy and alcohol septal ablation [ASA]).
The aim of HOCM pharmacological treatment is to decrease the obstruction to the left ventricular outflow tract (LVOT) in order to improve diastolic function and to improve systolic function by increasing stroke volume. This is achieved in approximately 50% of patients. Thanks to their negative chronotropic and inotropic effects, beta-blockers and calcium-channel blockers (especially verapamil) are efficient in reducing LVOT obstruction and mitral regurgitation during exertion. They are not as effective in patients with LVOT obstruction at rest.
Disopyramide is an antiarrhythmic drug with negative inotropic properties, which can diminish LVOT obstruction both at rest and during exertion. In this setting, disopyramide can be used in combination with either beta-blockers or with calcium-channel blockers when these fail to improve symptoms. However, in certain cases, an invasive strategy can be implemented in preference to the addition of disopyramide. Electrosystolic stimulation using a dual-chamber pacemaker can also be considered when pharmacological treatment has failed.2 The physiological mechanism by which LVOT obstruction is reduced includes improvement of diastolic filling pressures and a modified contraction sequence. In addition, pacemaker implantation enables the administration of higher doses of beta-blockers and calcium-channel blockers in patients with bradycardia or conduction abnormalities. However, the results of randomized studies assessing dual-chamber electrosystolic stimulation were disappointing. 3
Septal Reduction Strategies
Until the 1990s, surgical myomectomy was the gold-standard treatment of HOCM. This technique consists of scalpel resection of a segment of the interventricular septum. The left ventricle is accessed by means of an incision at the aortic root level with subsequent aortic valve retraction once extracorporeal circulation has been initiated. This surgical strategy reduces the obstruction to the outflow tract and relieves the resulting symptoms in 70%-90% of patients.4,5
Complication rates are low in high-volume expert centers, with 1%-2% mortality rates at 30 days, and long-term survival comparable to that of the general population without HOCM. The most feared complications are the occurrence of complete atrioventricular (AV) block (5%), ventricular septal defect (1%-2%), and postoperative aortic insufficiency. Although compelling, these surgical outcomes are generally achieved in a population of highly selected patients (young patients with few comorbidities).
ASA, which was first described by Ulrich Sigwart in 1994, is a purely chemical myomectomy whereby a therapeutic infarction is created at the level of the obstruction area in the basal septum.6 Over time, this technique has gradually become an attractive alternative to surgical myomectomy in patients with HOCM whose symptoms are refractory to optimal medical treatment. Since the latest European Society of Cardiology recommendations were issued in 2014, the surgical and interventional approaches have no longer been pitted against each other, but have appeared as two distinct septal ablation strategies that can be proposed in expert centers by the Heart Team, after considering patient status, risks inherent to each method, and the extent of abnormalities of the mitral valve apparatus.
Of note, the use of myomectomy and ASA is characterized by geographical variability, with certain centers being more experienced than others with one technique or the other. While surgical myomectomy is the preferred therapeutic strategy in the United States, ASA is more common in Europe and Asia.
ASA Indications and Contraindications
ASA indications and relative contraindications are listed in Table 1. In addition to these criteria, several other factors may influence the selection between these two invasive therapeutic modalities (Table 2). Factors in favor of ASA are advanced age, presence of comorbidities increasing the risks of cardiac surgery (ie, pulmonary disease), history of cardiac surgery, failed previous surgical myomectomy, or stroke. Patients who have received a pacemaker or a defibrillator are generally referred for ASA. This should also be the case for patients with a right bundle-branch block (RBBB), given the high risk of left bundle-branch block (LBBB) induced by surgical myomectomy and the subsequent need for pacemaker implantation. ASA is an appropriate option in patients with anatomical factors such as presence of a discrete septal bulge and a septal artery of suitable size and location. Conversely, surgical myomectomy is a preferable strategy in young patients (infants and adolescents) in the presence of the following factors: septum thickness >30 mm, mid-ventricular obstruction, valvular disease requiring repair or replacement, subvalvular or supravalvular aortic membrane, or coronary artery disease requiring coronary artery bypass graft surgery. Meticulous assessment of the mitral valve apparatus is recommended, given that 5%-15% of patients have severe abnormalities that may require surgical repair.
Myomectomy can also be considered in patients presenting with LBBB in view of the greater risk of pacemaker implantation after ASA, which often results in RBBB. In patients amenable to either treatment option, the patient’s own preference should be taken into account before selecting a therapeutic strategy.
ASA interventions are carried out in cardiac catheterization laboratories by interventional cardiologists experienced in such procedures. A minimum of 5-10 procedures per year are required per operator.7
Although the thoracic pain generated by the induced therapeutic infarction is of moderate intensity, it is recommended that the intervention be carried out under conscious sedation to preserve accurate hemodynamics, which are vital for the determination of procedural efficacy in real time. In addition, ASA should be performed with ultrasound guidance in order to increase the likelihood of success by selecting the septal branch(es) most suitable for treatment and to decrease the risk of complications by avoiding blind injections. Furthermore, use of echocardiography ensures continuous monitoring of gradients, ventricular kinetics, and the pericardium, and obviates the need for double arterial access or transseptal route for gradient measurement during the procedure. Preprocedural and postprocedural pressure gradients can be significantly lowered because of anesthesia, and the Valsalva maneuver can prove useful in unmasking gradients.8 In patients who do not have a permanent pacemaker or defibrillator, it is recommended that temporary transvenous pacing be delivered via the basilic, femoral, or jugular vein. This should be mandatory in patients with LBBB at baseline or in patients undergoing a redo procedure given the high risk of complete AV block. As temporary venous lead placement is not without risk, for selected patients with strictly normal conduction, the operators at our center use transcutaneous pacing patches for back-up pacing (provided careful ascertainment of their correct functioning has occurred). In addition, we can install a venous sheath at the beginning of the procedure, so placement of a temporary pacing lead can be performed quickly if needed.
The arterial access can be femoral or radial depending on operator preference and patient anatomy.9 At our center, the transradial approach has gradually replaced the femoral route (Figure 1),10 which has resulted in a lower incidence of vascular complications without affecting procedural success rates (Figures 2 and 3). Subsequently, a guiding catheter is introduced into the left main coronary artery. We typically select an Extra-Backup (EBU)-type catheter from the radial approach in order to achieve appropriate support. If femoral access is chosen, a Judkins left or EBU catheter may be used. Baseline angiography identifies the septal branch likely to supply the target septal area. In most cases, it is the first septal, which arises from the left anterior descending (LAD) coronary artery or, in some cases, from a diagonal, ramus intermediate, left main bifurcation, or (rarely) from the proximal right coronary artery (Figure 4). This is a very important phase of the procedure, as the selection of the septal artery or one of its branches is essential for procedural success. A 0.014˝ coronary wire is inserted into the selected septal. This maneuver can sometimes prove difficult because of the angle between the LAD and the septal branch, and the diameter of the LAD at this level. In this setting, an angulated microcatheter (SuperCross; Vascular Solutions) or a deflectable microcatheter (Venture; Vascular Solutions) can be used to direct the wire toward the septal branch. A short, coaxial balloon of a diameter slightly larger than the septal branch (generally between 1.5 and 2.5 mm) is then inserted over the wire in the selected septal branch. Very short balloons are recommended in order to avoid hyperselectivity in the presence of a septal branch with an early bifurcation. The balloon is subsequently inflated at low pressure (5 or 10 atm). A contrast injection is then performed to ensure that the balloon is fully occlusive, and the wire can be pulled out. Subsequently, 0.5-1 mL of pure contrast medium is injected into the central lumen of the balloon with a 2 mL syringe in order to: (1) ensure that the balloon is correctly positioned in the selected septal branch; (2) rule out the presence of collateral flow from the septal branch toward another branch of the left or right coronary system via numerous septal connections; and (3) confirm by concomitant echocardiography that the selected septal branch supplies the septal area obstructing the LVOT (echo-bright enhancement of the target septal area opposite the aliasing and systolic anterior movement apposition zone) (Figure 5).
After echocardiographic confirmation, 0.5-2 mL of absolute (pure) alcohol (>94°) are injected via the central lumen of the balloon (the stability of balloon position should be confirmed before starting the injection). The volume of alcohol is generally equal to the diameter of the septal branch (ie, 1.7 mL for a 1.7 mm septal branch). The alcohol should be injected very slowly at approximately 1 mL/min using a 1 mL syringe in order to differentiate the contrast and alcohol syringes and also for better injection velocity control. Slow injection velocity reduces the risks of periprocedural conduction abnormalities by preventing alcohol injection into septal connections. Stable positioning of both the balloon and the catheter should be checked throughout the procedure.
An assessment with the inflated balloon in place is required to evaluate the results of the ASA procedure 3-5 min after the end of the injection. Success is defined by a 50% reduction in the LVOT gradient by echocardiography (or invasive hemodynamics). In addition, the infarcted septal zone appears echo-bright. The electrocardiogram reveals a new RBBB in approximately 60% of cases with ST-segment elevation in leads V1-V3 and mirroring in the lateral leads. Transmural infarction and therefore RBBB are less likely if ASA is performed via a diagonal or ramus sub-branch of a septal.
Following slow rinsing of the balloon lumen with 0.2-0.5 mL of saline, the balloon is deflated and the last criterion of ASA success can be verified: the presence of “no-reflow” in the treated septal branch. If the gradient is reduced by <50% and the echo-bright zone is inadequate, the contrast enhancement zone of a second septal branch can be assessed in order to treat this branch during the same procedure (Figure 6). Table 3 summarizes the key elements of a successful procedure.
Postprocedural care and complications. Following completion of the procedure, patients are admitted to the coronary care unit for 3 days (1-2 days for patients who already have a permanent pacemaker) and a further 24-48 hr of monitoring on a general cardiology ward. Cardiac enzymes (CPK) should be regularly measured during this period. CPK elevation >1200 IU is common after the procedure. However, in patients with small septal bulges and small amounts of alcohol injections, CPK rise may be <1000 IU (closer to 800 IU). Redo ASA should not be performed because of insufficient CPK elevation. Clinical and echocardiographic results should dictate the need for a second procedure.
Beta-blockers should be continued or initiated even in the presence of transient AV block. The occurrence of AV block is by far the most frequent periprocedural or postprocedural complication. Most instances of AV block occurring during the procedure are reversible and the decision to implant a permanent pacemaker is often difficult. In patients with LBBB at baseline, the rate of pacemaker implantation is 25%-30%, as opposed to <5% in patients with a normal baseline electrocardiogram.
Patients in whom AV block does not resolve within 3 days generally receive a pacemaker. Patients are also monitored for the occurrence of high-grade or late complete AV block, as this requires a permanent pacemaker.
Patients are also monitored for the occurrence of ventricular arrhythmias despite the low frequency of this type of complication beyond 12 hours. Assessment of the risk of arrhythmia should normally be done before hospitalization for ASA as part of regular follow-up, but implantable defibrillator during the hospital stay may be considered for patients with sustained ventricular tachycardia >48 hours after the procedure. Patients are generally discharged after 5 days of continuous monitoring. The occurrence of complete AV block after day 5 is very rare.
Vascular complications are infrequent, especially in patients treated via the radial approach (in our center: 0.6% as opposed to 7.4% with the transfemoral route).10 Of note, these numbers represent all vascular complications, including inconsequential hematomas. In addition, femoral complication rates may be lower with modern closure devices in high-volume femoral centers. Other extremely rare complications11,12 are summarized in Table 4.
Long-term clinical outcomes. ASA has been associated with very promising long-term outcomes over the past few years (Figures 7 and 8). At our center, survival at 5 and 10 years was 94.1% and 86.9%, respectively, in a series of 240 patients with a mean age of 57 years. This represents a 1.3% mortality rate per year, which is comparable to that of the general French population matched for age and gender (Figure 9).10 The only predictor of mortality after ASA in our cohort was septum thickness (odds ratio, 1.17 per mm; P=.01). In comparison, in a recent study involving 470 patients with a mean age of 56 years, Jensen et al13 reported an 88% survival rate at 10 years (1.2% mortality per year, also comparable to that of the general population).
In their meta-analysis of 12 trials, Agarwal et al did not observe any differences in short-term or long-term mortality rates between ASA and surgical myomectomy. In addition, no differences were reported in terms of New York Heart Association (NYHA) functional class, ventricular arrhythmia, repeat intervention, or mitral insufficiency. The only difference between the two therapeutic modalities was the higher rate of permanent pacemaker implantation associated with ASA. In experienced centers, the success rate of ASA is above 90% and the risk of periprocedural mortality is lower than 1%. These results are comparable to those achieved with myomectomy in high-volume centers.14,15 A recent study evaluated the clinical success rate after ASA (survival in NYHA class I or II) in 166 patients with a mean age of 63 years.16 Predictive factors of clinical success were: (1) age >65 years; (2) LV-aorta gradient <100 mm Hg; (3) septum thickness <18 mm; and (4) LAD diameter <4 mm. Patients presenting with three or four of these factors had a 90.4% clinical success rate, as opposed to 57% in those with only one or two factors. The clinical success rate was also higher for patients treated by operators with previous experience of >50 cases.
Critics of ASA have hypothesized that the myocardial infarct scar could be a risk factor for arrhythmia and, therefore, sudden death. In this setting, several systematic reviews have compared the occurrence of sudden death in patients treated by ASA and those who underwent myomectomy.
A study by Leonardi et al showed a similarly low rate of sudden death with both therapeutic options.17 After adjustment for baseline characteristics, the risk of sudden cardiac death was found to be even lower in patients treated by ASA. In another recent study of 470 patients, the 0.5% annual rate of sudden death after ASA was similar to that of a reference population.13 These results have recently been confirmed in a large European registry.18,19 The authors pointed out the fact that ASA reduces the prevalence of certain risk factors for sudden cardiac death, ie, LVOT gradient, occurrence of non-sustained ventricular tachycardia (23% to 17%; P<.05), and septum thickness >30 mm (from 7% to 2%; P<.01). Finally, the findings of a recent study carried out by the Mayo Clinic suggest that ASA improves the natural course of HOCM by increasing the survival rate and decreasing the risk of sudden cardiac death.20
Since its inception more than 20 years ago, ASA has become a full-fledged therapeutic option for the treatment of HOCM. It can be selected as a primary invasive approach in many patients. When performed by an experienced team, ASA is associated with a high success rate and a low complication rate. Improvements in quality of life are durable and life expectancy is comparable to a similarly aged general population.
1. Authors/Task Force members, Elliott PM, Anastasakis A, et al. 2014 ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014;35:2733-2779.
2. Fananapazir L, Epstein ND, Curiel RV, Panza JA, Tripodi D, McAreavey D. Long-term results of dual-chamber (DDD) pacing in obstructive hypertrophic cardiomyopathy. Evidence for progressive symptomatic and hemodynamic improvement and reduction of left ventricular hypertrophy. Circulation. 1994;90:2731-2742.
3. Nishimura RA, Trusty JM, Hayes DL, et al. Dual-chamber pacing for hypertrophic cardiomyopathy: a randomized, double-blind, crossover trial. J Am Coll Cardiol. 1997;29:435-441.
4. Maron BJ, Maron MS, Wigle ED, Braunwald E. The 50-year history, controversy, and clinical implications of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy from idiopathic hypertrophic subaortic stenosis to hypertrophic cardiomyopathy: from idiopathic hypertrophic subaortic stenosis to hypertrophic cardiomyopathy. J Am Coll Cardiol. 2009;54:191-200.
5. McCully RB, Nishimura RA, Tajik AJ, Schaff HV, Danielson GK. Extent of clinical improvement after surgical treatment of hypertrophic obstructive cardiomyopathy. Circulation. 1996;94:467-471.
6. Sigwart U. Non-surgical myocardial reduction for hypertrophic obstructive cardiomyopathy. Lancet. 1995;346:211-214.
7. Harold JG, Bass TA, Bashore TM, et al. ACCF/AHA/SCAI 2013 update of the clinical competence statement on coronary artery interventional procedures: a report of the American College of Cardiology Foundation/American Heart Association/American College of Physicians Task Force on Clinical Competence and Training (Writing Committee to Revise the 2007 Clinical Competence Statement on Cardiac Interventional Procedures). J Am Coll Cardiol. 2013;62:357-396.
8. Holmes DR Jr, Valeti US, Nishimura RA. Alcohol septal ablation for hypertrophic cardiomyopathy: indications and technique. Catheter Cardiovasc Interv. 2005;66:375-389.
9. Cuisset T, Lefèvre T. Contemporary techniques for catheter-based intervention for hypertrophic obstructive cardiomyopathy. EuroIntervention. 2016;12(Suppl X):X44-X47.
10. Sawaya FJ, Louvard Y, Spaziano M, et al. Short and long-term outcomes of alcohol septal ablation with the trans-radial versus the trans-femoral approach: a single center-experience. Int J Cardiol. 2016;220:7-13.
11. Ommen SR, Maron BJ, Olivotto I, et al. Long-term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. 2005;46:470-476.
12. Woo A, Williams WG, Choi R, et al. Clinical and echocardiographic determinants of long-term survival after surgical myectomy in obstructive hypertrophic cardiomyopathy. Circulation. 2005;111:2033-2041.
13. 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;99:1012-1017.
14. 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;55:823-834.
15. Alam M, Dokainish H, Lakkis NM. Hypertrophic obstructive cardiomyopathy-alcohol septal ablation vs. myectomy: a meta-analysis. Eur Heart J. 2009;30:1080-1087.
16. 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.
17. Leonardi RA, Kransdorf E, 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. Circ Cardiovasc Interv. 2010;3:97-104.
18. Veselka J, Jensen MK, Liebregts M, et al. Long-term clinical outcome after alcohol septal ablation for obstructive hypertrophic cardiomyopathy: results from the Euro-ASA registry. Eur Heart J. 2016;37:1517-1523.
19. 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. 2014;84:101-107.
20. Sorajja P, Ommen SR, Holmes DR Jr, et al. Survival after alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Circulation. 2012;126:2374-2380.
From the Ramsay Générale de Santé, Interventional Cardiology Department, Institut Cardiovasculaire Paris-Sud, Hôpital Privé Jacques Cartier, Massy, France.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript submitted January 19, 2017, provisional acceptance given February 15, 2017, final version accepted April 11, 2017.
Address for correspondence: Dr Thierry Lefèvre, Hôpital Privé Jacques Cartier, 6 Avenue du Noyer Lambert 91300, Massy, France. Email: firstname.lastname@example.org