Hypertrophic cardiomyopathy alcohol septal ablation

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [mailto:mgibson@perfuse.org]; Cafer Zorkun, M.D. [mailto:zorkun@perfuse.org]; Caitlin J. Harrigan [mailto:charrigan@perfuse.org]; Martin S. Maron, M.D.; Barry J. Maron, M.D.;

Overview
Alcohol septal ablation is a percutaneous technique that involves injection of alcohol into the first septal perferator of the left anterior descending artery. This is a technique with results similar to the surgical septal myectomy procedure but is less invasive, since it does not involve general anaesthesia and opening of the chest wall and pericardium (which are done in a septal myomectomy). In a select population with symptoms secondary to a high outflow tract gradient, alcohol septal ablation can reduce the symptoms of HCM. When performed properly, an alcohol septal ablation induces a controlled heart attack, in which the portion of the interventricular septum that involves the left ventricular outflow tract is infarcted and will contract into a scar.

History
Alcohol septal ablation was first performed in Britain at the Royal Brompton Hospital by Ulrich Sigwart in 1994. Since that time, it has quickly gained favor among physicians and patients alike due to its minimally-invasive nature, avoiding general anesthesia, lengthy recuperation and other complications associated with open heart surgery (septal myectomy).

Technique
Alcohol septal ablation is performed in the cardiac catheterization laboratory, and should only be performed by interventional cardiologists with specific training in the procedure. As such, it is only available in a few institutions. The technique is similar to coronary angioplasty, and utilizes similar equipment. Using wires and balloons to localize the septal artery feeding the diseased muscle, a small amount of absolute alcohol is infused into the artery to produce a small heart attack. Patients typically experience mild chest discomfort during the procedure, which takes approximately 30 minutes to complete. Analesics and mild sedatives are administered as needed. Patients typically are maintained in the hospital for three to four days to monitor for any complications, including need for permanent pacemaker in 5-10%.

Efficacy and Procedural Success
Relief of obstruction is noted immediately in the majority of appropriately selected patients. Clinical success is defined as a 50% or more reduction in peak gradient across the outflow tract, predicting continued improvement in gradient and cardiac remodeling over the ensuing 1 to 2 years. Over 90% of patients experience a successful procedure, with improvement in outflow tract gradient and mitral regurgitation. Patients typically report progressive reduction in symptoms, including improved shortness of breath, lightheadedness and chest pain.

Follow-Up
Serial echocardiograms are routinely obtained to follow the cardiac remodeling over time, and document reduction in outflow tract gradient.

1. Atrioventricular block

 * Secondary to induction of a therapeutic infarction and thinning of the proximal interventricular septum due to the procedure

2. Complete heart block

 * Observed in 50% of patients during the procedure.


 * Persistent complete heart block requiring pacemaker implantation is observed in 10% - 20% of patients.

3. Ventricular tachyarrhythmias

 * The risk of arrhythmias in patients with HOCM significantly increases secondary to the ventricular arrhythmogenic potential of the scar that is formed post-ablation.


 * Approximate 3% - 10% risk of developing sustained ventricular arrhythmias        and sudden cardiac death following ablation was observed in patients with or without the risk for sudden cardiac death.


 * The in-hospital mortality rate is up to 2% in patients who develop sustained ventricular tachycardia.    In contrast, the rate of sustained ventricular arrhythmias following myectomy is as low as 0.2% to 0.9% per year.

Supportive trial data

 * In a single-center study that enrolled ninety-one consecutive patients (aged 54+/-15 years) with obstructive hypertrophic cardiomyopathy underwent either alcohol septal ablation or septal myectomy to evaluate the long-term outcomes of the procedure. During a follow-up period of 5.4+/-2.5 years, the study demonstrated 21% of patients experienced sudden or other cardiac death and aborted sudden cardiac death including appropriate cardioverter-defibrillator discharges for fast ventricular tachycardia or ventricular fibrillation. The 1-, 5-, and 8-year survival-free from the primary end point was: 96%, 86%, and 67%, respectively in patients treated with septal ablation versus 100%, 96%, and 96%, respectively in patients treated with septal myectomy during 6.6+/-2.7 years (log-rank, P=0.01). The annualized event rate after ablation was reported to be 4.4% per year with an approximate 5-fold increase in the estimated annual primary end point rate (4.4% versus 0.9%) when compared with myectomy patients.


 * Another cohort single-center study, examined the rates of sudden cardiac death among 89 patients treated with alcohol septal ablation. The secondary end point of the study was the incidence of ventricular tachycardia or ventricular fibrillation, the need for appropriate implantable cardioverter defibrillator (ICD) therapy, or cardiac arrest following septal ablation among those with [Hypertrophic cardiomyopathy automatic implantable cardiac defibrillator placement|implanted ICDs]] or permanent pacemakers (n = 42). No mortality was attributable to sudden cardiac death at a mean follow-up of 5.0 +/- 2.3 years. Among the 42 patients with an ICD or permanent pacemaker, 9 reported documented VT/VF, cardiac arrest, or appropriate ICD therapy, resulting in an annual event rate of 4.9%/year. A 10-mm Hg increase in the immediate post-septal ablation gradient was shown to be associated with a hazard ratio of 2.66 for arrhythmic events (95% confidence interval 1.55 to 4.56, p <0.001).


 * Meta-analyses of septal reduction therapies that included 19 septal ablation studies (2207 patients) and 8 surgical myectomy studies (1887 patients) was performed to compare the rates of overall mortality and sudden cardiac death after treatment. The median follow-up was shorter for ablation than for myectomy studies (51 versus 1266 patient-years; P<0.001). No significant difference was observed in the incidence of sudden cardiac death and all-cause mortality between the two groups.


 * Another recent meta-analysis of 12 studies that compared the two septal reduction therapies reported similar results with no significant difference observed in the short-term and the long-term mortality between two groups. However, septal ablation was found to increase the risk of right bundle branch block (pooled odds ratio: 56.3; 95% CI: 11.6 to 273.9) along with the need for permanent pacemaker implantation post-procedure (pooled OR: 2.6; 95% CI: 1.7 to 3.9).

4. Itragenic ventricular septal defect

 * Alcohol septal ablation is contra-indicated in patients with a septal thickness of greater than 15mm because of the potential for creating a ventricular septal defect.

Comparison to Myectomy

 * Non-randomized data from the Netherlands suggests caution in the utilization of alcohol septal ablation, which may be inferior to surgical myectomy . The outcomes (the risk of cardiac death and aborted sudden cardiac death including appropriate cardioverter-defibrillator discharges for fast ventricular tachycardia/ventricular fibrillation) in 91 consecutive alcohol septal ablation patients were compared with 40 patients who underwent septal myectomy. The 1-, 5-, and 8-year event free survival was 96%, 86%, and 67%, respectively in the alcohol septal ablation patients which was poorer than the 100%, 96%, and 96%, event free rates in the myectomy patients over 6.6±2.7 years (P=0.01). Stated differently, the alcohol septal ablation patients faced a 5-fold increase in the risk of the primary endpoint on an annual basis (4.4% versus 0.9%) even when adjustments were made in a propensity adjusted multivariable model (p=0.02).  Based upon non-randomized data, myectomy may be prefferable to alcohol septal ablation.


 * The hypertrophied muscle is directly visible and resected; however, with success rate of septal ablation is dependent on the anatomy of the septal artery which is variable in approximately 20% to 25% of patients.

'It is important to note that patients who fail to respond to alcohol septal ablation may still be candidates for surgical myectomy. Likewise, patients who fail surgical myectomy may still respond to alcohol septal ablation.'

==2011 ACCF/AHA Guideline Recommendations: Alcohol Septal Ablation ==

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Class IIa
1. Consultation with centers experienced in performing both surgical septal myectomy and alcohol septal ablation is reasonable when discussing treatment options for eligible patients with HCM with severe drug-refractory symptoms and LVOT obstruction. (Level of Evidence: C)

2. When surgery is contraindicated or the risk is considered unacceptable because of serious comorbidities or advanced age, alcohol septal ablation, when performed in experienced centers, can be beneﬁcial in eligible adult patients with HCM with LVOT obstruction and severe drug-refractory symptoms (usually NYHA functional classes III or IV).(62,153,277–281) (Level of Evidence: B)

Class IIb
1. Alcohol septal ablation, when performed in experienced centers, may be considered as an alternative to surgical myectomy for eligible adult patients with HCM with severe drug-refractory symptoms and LVOT obstruction when, after a balanced and thorough discussion, the patient expresses a preference for septal ablation.(153,273,278,280,281) (Level of Evidence: B)

2. The effectiveness of alcohol septal ablation is uncertain in patients with HCM with marked (i.e., >30 mm) septal hypertrophy, and therefore the procedure is generally discouraged in such patients. (Level of Evidence: C)

Class III (Harm)
1. Alcohol septal ablation should not be done in patients with HCM with concomitant disease that independently warrants surgical correction (e.g., coronary artery bypass grafting for CAD, mitral valve repair for ruptured chordae) in whom surgical myectomy can be performed as part of the operation. (Level of Evidence: C)

2. Alcohol septal ablation should not be done in patients with HCM who are less than 21 years of age and is discouraged in adults less than 40 years of age if myectomy is a viable option. (Level of Evidence: C)}}

Guideline Resources

 * ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities


 * The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in Collaboration with the European Heart Rhythm Association


 * 2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy