General description of procedure, equipment, technique

  • Symptomatic hypertrophic cardiomyopathy (HCM) is due to significant obstruction to flow in the left ventricular outflow tract (LVOT).
  • This obstruction results from a thickened interventricular septum (IVS) and systolic anterior motion (SAM) of the mitral valve (most commonly the anterior mitral apparatus).
  • Mitral regurgitation resulting from SAM also contributes to the pathophysiology of HCM.
  • Percutaneous intervention for HCM involves creating a localized infarction of the portion of interventricular septum that is in contact with the mitral valve.
  • By substantially reducing the thickness of the septum (due to scarring) and decreasing contraction of the pathologic portion of the IVS, the degree of SAM is also diminished and the LVOT gradient is reduced.
  • Possible methods for creating an infarct include: coiling of the septal artery, which perfuses the region of interest; infusion of cyanoacrylate glue, gelatin, or alcohol into the septal artery; and radiofrequency ablation or cryoablation of the septal tissue
  • Of the above, alcohol septal ablation (ASA) has shown the most promising results.
  • ASA involves the infusion of small amounts (1 to 3 cc) of absolute alcohol in the septal artery perfusing the IVS at the region of interest.
  • The procedure requires femoral arterial access for placement of a coronary guide catheter and a pigtail catheter (for simultaneous left ventricular [LV] and aortic pressure measurement), as well as femoral or jugular venous access for placement of a transvenous pacemaker in case of conduction abnormalities due to the procedure.

Indications and patient selection

  • The first line of therapy for patients with HCM is medical treatment with beta-blockers, calcium-channel blockers, disopyramide, or some combination of the three.
  • In patients who remain symptomatic despite optimal medical treatment, septal reduction therapy is recommended.
  • ASA is recommended for patients who meet the following criteria:LVOT gradient >30 mmHg (resting or provoked) due to septal thickening and SAM causing LVOT obstruction.Septal thickness >16 mm (but <30 mm).

    Presence of a septal perforator that provides perfusion to the obstruction-causing area of the IVS

    Absence of significant mitral valve pathology or abnormal papillary muscle anatomy

    Patients with surgical risk that is high or prohibitive

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    Patients who have a strong preference against open-heart surgery

    Absence of surgical expertise for performing myectomy and necessary adjunctive operations safely and effectively

  • ASA is provided a Class IIb indication for patients with drug-refractory HCM symptoms in the 2011 American College of Cardiology/American Heart Association guidelines.
  • The procedure should be performed at referral centers with a large experience in ASA.


The following are contraindications to alcohol septal ablation for symptomatic HCM:

  • Large septal perforator that provides blood flow to a much larger area than the focused area of interest of the septum.
  • Patients with coronary circulation that is dependent on collateral filling provided by the septal perforator in the region of interest for septal ablation.
  • Patients without a septal perforator providing blood flow to the septal region of interest.
  • Factors responsible for the gradient other than, or in addition to, septal hypertrophy (e.g., cavity obstruction due to generalized hypertrophy, mitral valve pathology, such as an enlarged leaflet with anterior displacement of coaptation line or papillary muscle malpositioning.
  • Septal thickness >30 mm (unclear effectiveness) or <15 mm (increased risk of ventricular septal defect).

Details of how the procedure is performed

  • The patient should be consented for the major complications of the ASA procedure including: vascular access complications, complications of contrast dye use, myocardial infarction (due to the risk of alcohol infusion beyond the septal perforator of interest), guide catheter complications (including coronary dissection or stroke), conduction abnormalities requiring permanent pacemaker implantation, and the risks of temporary transvenous pacemaker implantation.
  • ASA is conducted under conscious sedation, but care must be taken to provide adequate pain relief from the myocardial infarction that is caused by the procedure.
  • ASA is performed in the cardiac catheterization laboratory using angiography and transthoracic echocardiography (TTE) guidance, though some operators have used transesophageal echocardiography (TEE) or intracardiac echocardiography (ICE).
  • The procedure is routinely conducted via dual arterial access: one for using a 6-Fr guide catheter to engage the left main coronary artery (LMCA), and the other for introducing a pigtail catheter (5- or 6-Fr) into the LV for simultaneous LV:aorta gradient measurement.
  • Femoral or jugular venous access should also be obtained for placement of a temporary transvenous pacemaker (usually kept in place for 2 days after the procedure).
  • Intravenous unfractionated heparin should then be administered to achieve an activated clotting time (ACT) of 250 to 300 seconds.
  • The LMCA is engaged with the guide and a coronary wire is advanced to the septal branch (usually the first septal perforator) of interest (Figure 1) (A).
  • An over-the-wire (OTW) coronary balloon (slightly larger in diameter than the septal branch) is then advanced over the wire and inflated in the proximal portion of the septal until the vessel is successfully occluded (Figure 1) (B).
  • After removal of the coronary wire, dye is injected into the septal branch via the OTW balloon to provide assurance that there is no reflux of dye (and therefore alcohol) to the left anterior descending (LAD) (Figure 1) (C).
  • Additionally, the operator should be certain that the septal branch does not provide major collateral filling to another territory.
  • Echocardiographic contrast dye is then injected via the OTW balloon to highlight the area of myocardium subtended by the septal branch, which is evaluated on the TTE (Figure 2).
  • If the region supplied by the septal branch does not correspond to the area of interest in the IVS on the echocardiogram, care should be taken to evaluate another septal branch.
  • Once the above precautions have been taken, the operator infuses 1 cc of absolute alcohol via the OTW balloon.
  • The LVOT gradient by TTE and the LV:aorta pressure-gradient are then measured; if necessary, another 1 cc of alcohol can be infused.
  • The OTW balloon should remain inflated for the duration of the alcohol infusion and for 5 to 10 minutes after the last infusion to minimize the risk of any reflux into the LAD.
  • Once the procedure has been completed, angiography of the left coronary system should be performed to assure the operator that there has been no unintended consequences (usually due to alcohol reflux down the LAD (Figure 1) (D).
  • Closure of the arterial sites may be performed using closure devices at the conclusion of the procedure, or using manual compression hemostasis once coagulation time has returned to normal.
  • The patient should be transferred to the intensive care unit for monitoring with the transvenous pacemaker left in place in case of conduction block that may occur up to 2 to 3 days after the procedure.
  • Monitoring of the patient after the procedure includes evaluation of the arterial and venous access sites, continuous telemetry, and TTE to document the reduction in LVOT gradient (and mitral regurgitation if applicable).
  • Discharge on postprocedural day 3 or 4 is reasonable if clinically appropriate.
Figure 1.
Alcohol septal ablation (ASA). (A) Initial angiography reveals a large septal perforator (arrows) that corresponds to the septal area of interest. (B) A balloon (arrow) is passed over the wire (arrowhead) into the septal and inflated, obstructing flow of contrast into the septal. (C) Contrast injection via the inflated balloon reveals filling of the septal (arrow) without reflux into the LAD. (D) After ASA, the septal is occluded (arrow).

Figure 2.
Transthoracic echocardiography during alcohol septal ablation (ASA). (A) the area of septal-mitral valve contact is identified (arrow). (B) Injection of echocardiographic contrast via an over-the-wire balloon in the septal highlights the area of interest (arrow).

Interpretation of results

  • When the balloon is inflated in the appropriate septal perforator, a significant drop in resting gradient (often >50%) is a good prognosticator for effective ASA; but a lack of decrease in the gradient does not imply that the septal is inadequate for ASA.
  • If the initial alcohol injection results in complete heart block or significant conduction abnormality (bifascicular block with prolonged P–R interval), consideration should be given to not injecting any more alcohol with the hope of conduction returning and preventing the need for a permanent pacemaker.
  • Once the balloon is removed, the resting and provoked gradient should be remeasured. If there is a <50% reduction in the gradient, consideration should be given to injection of another septal perforator.
  • We use amyl nitrate inhalation to provoke the gradient by breaking the vial and holding it in front of the patient’s nose until a significant drop in blood pressure (BP) is achieved. Dobutamine has been used but is less useful in our opinion.

Outcomes (applies only to therapeutic procedures)

  • The first results of ASA for HCM were published in 1995 by Ulrich Sigwart, who performed the procedure in three patients, all of whom demonstrated near-complete obliteration of the LVOT gradient and good recovery in functional class.
  • Since that time, a number of observational series of ASA and nonrandomized comparisons with SM have been published.
Efficacy and safety of alcohol septal ablation
  • A meta-analysis of 42 trials, which included a total of 2,959 patients, was notable for the significant and durable improvement in LVOT gradient, albeit with a higher risk for permanent pacemaker implantation compared with the surgical series (approximately 5%):Reduction in resting LVOT gradient from 65.3 mmHg to 17.1 mmHg post-ASA and 15.1 mmHg at 24 months.Reduction in provoked gradient from 125.4 mmHg to 53.4 mmHg post-ASA and 28.4 mmHg at 24 months.

    Improvement in New York Hospital Association (NYHA) class from 2.9 to 1.4 at 3 months and 1.2 at 12 months.

    Decrease in size of the IVS from 20.9 mm to 16.5 mm at 3 months and 13.9 mm at 12 months.

    In-hospital mortality was 1.5%, 46.2% of patients developed a new right-bundle branch block (RBBB), and 10.5% required placement of a permanent pacemaker (PPM).

    Repeat ASA was needed in 6.6% of patients, and 2% of patients went on to have a surgical myectomy.

  • Most recently, findings were reported for the Multicenter North American Registry of ASA for HCM, which enrolled 874 patients who experienced a significant reduction in LVOT gradient and improvement in NYHA class, with mortality rates comparable to those of the surgical series and better than patients left untreated in other series:The patients had an average age of 55 years, with resting and provoked gradients of 70 mmHg and 99 mmHg, and 78% of patients had an NYHA class of III or IV.After ASA, the resting gradient had fallen to 35 mmHg and only 4.6% of patients had an NYHA class >/= III.

    Mortality at 5 years was 14%, with two thirds of deaths due to either noncardiac or unidentified causes; this is better than the 21%, 5-year mortality for HCM patients left untreated shown in other series.

    12.8% (112) of patients required repeat ASA on clinical grounds, and 2.9% (25) went on to surgical myectomy.

    PPM implantation was required in 8.9% of patients, and 10.8% (94) required ICD implantation due to accepted risk factors for sudden cardiac death (SCD) in patients with HCM.

    Multivariate predictors of increased mortality included: baseline NYHA class (HR 1.63), post-ASA septal thickness at 3 months (HR 1.21), number of ASA procedures (HR 1.66), and beta-blocker use post-ASA (HR 1.32).

    Predictors of decreased mortality included: baseline EF (HR 0.98) and number of arteries injected (HR 0.78).

Comparisons of alcohol septal ablation to surgical myectomy
  • No studies have directly compared ASA to surgical myectomy (SM) in a randomized fashion.
  • Therefore, while observational series and nonrandomized comparisons provide an important contribution to the literature, these studies are subject to the biases inherent to nonrandomized comparisons.
  • In an analysis of 55 patients with high surgical risk (due to advanced age or other significant comorbidities) who underwent ASA, Kwon and colleagues demonstrated significant improvements in LVOT gradient and functional class with mortality comparable to a propensity-matched group of patients undergoing SM:The ASA patients had a mean age of 63 years and 96% had an NYHA class >/= III.At 1-month, there was a reduction in the resting LVOT gradient from 72 to 31 mmHg and in the provoked gradient from 104 to 49 mmHg.

    The percentage of patients with NYHA class >/= III decreased from 96% to 17% with ASA.

    Of the 55 patients, 1 (2%) had died at 1 month, 2 (4%) at 1 year, 7 (13%) at 5 years, and 13 (24%) at 10 years, mostly of noncardiac or unknown causes; this was similar to the published mortality rates of patients undergoing SM (1.5% to 3.5% per year).

    The authors performed propensity matching using a group of patients who had undergone SM over the same time period (n = 28 in each group), and found no difference in mortality between ASA and SM.

    PPM implantation was necessary in 14 (25.5%) patients, 13 of whom were dependent on the pacemaker at 3-month follow-up.

    Nine patients (16%) required repeat procedures over 10 years of follow-up due to persistent symptoms: five underwent repeat ASA, three underwent SM, and one had mitral valve surgery.

  • In a similar study, Sorajja and colleagues identified 138 patients who had undergone ASA, and were able to age- and gender-match 123 of them to 123 patients who had undergone SM.
  • Overall, patients undergoing ASA experienced similar overall survival, but patients <65 years of age had lower rates of the combined endpoint of survival and freedom from severe symptoms, as well as higher rates of PPM implantation:The average ASA patient was 64 years old and 99% of ASA patients had an NYHA class >/= III.The LVOT gradient decreased from 80 mmHg to 10 mmHg, with resulting decrease in median NYHA class from 3.0 to 1.5; 92% of patients had an NYHA class </= II after ASA.

    Periprocedural death was noted in 1.4% of cases, and mortality at 2 years after ASA was 6.5% (including ICD discharge for VT/VF), and at 4 years was 12%.

    Five patients underwent redo ASA, and nine patients went on to have SM (including two emergently due to perforation during ASA).

    By comparison, the SM group had an average age of 60 years, with a resting gradient of 55 mmHg and significantly lower rates of hypertension (52.8 vs. 24.8%) and CAD (13.8 vs. 2.4%) compared with the ASA group.

    In the overall population, there was no significant difference in the 4-year survival rate between ASA and SM (86.4 vs. 94.3%, P = .18), or the combined endpoint of survival and freedom from severe symptoms at 4 years (76.4 vs. 82.5%, P = .27).

    However, in the subgroup of patients <65 years old, survival and freedom from severe symptoms was better for patients who had undergone SM (71 vs. 88.5%, P = .01).

    With respect to the need for PPM implantation, the rate was higher in patients undergoing ASA (20.2 vs. 2.4%), though the authors note that their threshold for PPM implantation was lower than in other published series; using the criteria from other investigators, their PPM implantation rate would have been 12%.

  • A meta-analysis of studies comparing ASA to SM was performed by Agarwal and colleagues, who noted similar survival and functional class improvement with ASA, but also a higher rate of PPM implantation and a higher postprocedural LVOT gradient:Among the 12 studies included in their analysis, 410 patients underwent ASA and 398 patients underwent SM.There was a significantly higher LVOT gradient after ASA, though a comparison of net reduction in LVOT gradient yielded no significant difference between the two groups.

    There was a significantly greater odds of PPM implantation in the ASA group (OR 2.6; CI 1.7 to 3.9).

    There was no significant difference in short- or long-term mortality between the two groups.

    There was no significant difference in functional status between the two groups.

    There was no significant difference in the rate of ventricular arrhythmia or MR grade between the 2 groups.

Alternative and/or additional procedures to consider

Surgical myectomy
  • SM was first developed in the 1960s.
  • Surgical myectomy (SM) is still considered the first-line therapy for these patients (ACC/AHA Class IIa recommendation), and is therefore recommended for symptomatic patients who are younger and without comorbid illnesses, or patients with significant mitral valvular pathology or coronary disease that requires concomitant treatment along with SM.
  • A large series of patients undergoing SM at a tertiary care referral center with expertise in SM showed the following:Of 1,337 patients with HCM, 289 symptomatic patients underwent SM.The mean LVOT gradient decreased from 67 to 3 mmHg, and the number of patients with NYHA class >/= III decreased from 89% to 6%.

    Operative mortality was 0.8% and the survival rate at 1-, 5-, and 10-years was 98%, 96%, and 83%.

  • Surgery for patients with symptomatic HCM has been granted a Class IIa recommendation in the 2011 ACC/AHA HCM guidelines.
Choice of alcohol septal ablation or surgical myectomy
  • The outcomes of ASA and nonrandomized comparisons of ASA to SM have been discussed above.
  • Whether to choose ASA or SM is dependent on a number of factors.
  • Overall, young patients with isolated HCM might be best served by SM, and older patients with comorbid illness or other high-risk patients may be best served by ASA.
  • Institutional experience with either ASA or SM and the risks and outcomes of each is an important consideration; some centers (or countries) are much more comfortable with one procedure or the other.
  • In either case, the procedure should be performed by operators at a tertiary referral center with high volume.
  • Anatomy is another important consideration: patients who have significant intrinsic mitral valve disease, obstruction due to a displaced or accessory papillary muscle, or do not have appropriate septal perforator anatomy for ASA would all benefit from choosing SM over ASA.
  • Patients with combined disease (i.e., HCM and valvular heart disease or coronary artery disease) may benefit from an all-surgical or all-percutaneous approach, depending on clinical characteristics, risk:benefit ratios of each approach, and patient preference.
  • Patient preference for ASA or SM is also an important consideration given the overall good outcome of both procedures, but a thorough discussion must be conducted to address the risks and benefits of both prior to any decision-making.
Options after unsuccessful alcohol septal ablation
  • Between 5% and 15% of patients do not have adequate clinical benefit from the ASA procedure.
  • In these cases, a thorough evaluation should be conducted to determine the nature of the treatment failure before deciding upon the management strategy.
  • If failure is due to inadequate reduction in LVOT gradient, but a reduction has occurred and there is appropriate septal anatomy for repeat alcohol infusion, then a redo of ASA may be considered.
  • However, if failure is the result of inadequate septal perforator supply to the myocardium of interest, or if due to significant MV disease, then repeat ASA is also likely to be unsuccessful and SM should be considered.
  • Nagueh and colleagues performed an analysis of 20 patients who required SM after ASA (out of 375 total patients undergoing ASA, 9 of whom had undergone 2 ASA procedures), and determined that SM could be safely performed but with a higher rate of needing PPM implantation than patients undergoing primary SM (10% vs. 1% to 2%).

Complications and their management

  • The mortality rates of ASA in various registries and meta-analyses are presented above.
  • The major complications of ASA and their incidence in the North American Multicenter Registry of ASA for HCM are summarized below.
  • The most common complication after ASA is the occurrence of complete heart block (CHB; incidence discussed above) requiring implantation of a PPM.
  • Since ASA often creates a right-bundle branch block (RBBB), patients with preexistent left-bundle branch block (LBBB) are at higher risk for CHB.
  • The ASA procedure therefore always begins with the insertion of a temporary RV pacing lead (in patients without a PPM).
  • Because CHB may occur up to 48 to 72 hours after the procedure, patients should be monitored with telemetry and with the temporary lead in place for that period of time.
  • Ventricular tachycardia/fibrillation is a known complication of HCM; ASA has not been found to increase the risk of these ventricular arrhythmias.
Coronary complications
  • Coronary dissection/perforation due to either the guide catheter, coronary wire, or balloon catheter is rare, occurring <1% of the time.
  • In cases of dissection, prolonged balloon inflation and stent placement usually is adequate. In some cases placement of a covered stent may be required. If open heart surgery is necessary to seal the perforation due to inadequate percutaneous therapy, consideration should be given to leaving the balloon inflated in place until the patient is on cardiopulmonary bypass.
  • Leakage of alcohol into the LAD is a significant concern, and is minimized by ensuring adequate balloon dilation in the ostial/proximal septal branch followed by injection of contrast via the balloon to confirm no leak back into the LAD (Figure 1) (C).
Ventricular septal defect
  • The risk of ventricular septal defect (VSD) with ASA is quite low, and is due to excess infarction in the IVS subtended by the septal perforator.
  • Prompt diagnosis should be made by transthoracic echocardiography and/or intracardiac oxygen shunt run.
  • If clinically significant, repair is usually performed surgically.
  • Due to the concern for creation of a ventricular septal defect (VSD), the ASA procedure should not be performed if the IVS is <15 mm in thickness.
Cardiac tamponade
  • Tamponade is most commonly due to perforation of the right ventricle (RV) by the temporary pacemaker.
  • This risk can be minimized by instituting anticoagulation only after pacemaker implantation has been completed.
  • Coronary artery perforation should also be suspected and evaluated.
  • Vigilant monitoring of the pericardial space should be performed using echocardiography throughout the ASA procedure.
  • In addition to treatment of the underlying cause, pericardiocentesis may be necessary if clinical signs of tamponade are present.
Vascular complications
  • The rate of vascular complications at the femoral access site is similar to that with percutaneous coronary intervention.
  • In the North American Registry, 0.8% of patients experienced a complication such as arteriovenous (AV) fistula, femoral artery pseudoaneurysm, groin hematoma, and retroperitoneal hematoma.
  • Management of vascular complications may include any or all of the following: balloon angioplasty or stenting for dissection or perforation, thrombin injection of pseudoaneurysm or surgical aneurysmectomy, surgical repair of vascular perforation, and blood transfusion.
Cerebrovascular accident
  • Stroke/TIA is a known complication of coronary interventions, usually due to dislodgement of the ascending aorta or arch atheroma during advancement of wires and guide catheters.
  • As with all coronary interventions, a thorough neurologic exam should be performed before and after the procedure.
  • If stroke/TIA is suspected, emergent neurologic imaging and consultation should be obtained.

What’s the evidence?

Agarwal, S, Tuzcu, EM, Desai, MY. “Updated meta-analysis of septal alcohol ablation versus myectomy for hypertrophic cardiomyopathy”. J Am Coll Cardiol. vol. 55. 2010. pp. 823-34. (Recent meta-analysis comparing ASA and SM.)

Sorajja, P, Valeti, U, Nishimura, RA. “Outcome of alcohol septal ablation for obstructive hypertrophic cardiomyopathy”. Circulation. vol. 118. 2008. pp. 131-9. (Single-center comparison of ASA and SM.)

Sigwart, U. “Non-surgical myocardial reduction for hypertrophic obstructive cardiomyopathy”. Lancet. vol. 346. 1995. pp. 211-4. (Seminal first-paper describing ASA for HCM.)

Nagueh, SF, Groves, BM, Schwatz, L. “Alcohol septal ablation for the treatment of hypertrophic obstructive cardiomyopathy: A multicenter North American registry”. J Am Coll Cardiol. vol. 58. 2011. pp. 2322-8. (Largest multicenter registry describing outcomes of ASA for HCM.)

Kwon, DH, Kapadia, SR, Tuzcu, EM. “Long-term outcomes in high-risk symptomatic patients with hypertrophic cardiomyopathy undergoing alcohol septal ablation”. J Am Coll Cardiol Intv. vol. 1. 2008. pp. 432-8. (Single-center study of ASA in HCM patients who are high-risk for SM.)

Alam, M, Dokainish, H, Lakkis, N. “Alcohol septal ablation for hypertrophic obstructive cardiomyopathy: a systematic review of published studies”. J Interven Cardiol. vol. 19. 2006. pp. 319-27. (Meta-analysis of most published data on ASA for HCM.)

Nagueh, SF, Buergler, JM, Quinones, MA, Spencer, WH, Lawrie, GM. “Outcome of surgical myectomy after unsuccessful alcohol septal ablation for the treatment of patients with hypertrophic obstructive cardiomyopathy”. J Am Coll Cardiol. vol. 50. 2007. pp. 795-8. (Provides data regarding outcomes of SM after unsuccessful ASA.)

Gersh, BJ, Maron, BJ, Bonow, RO. “2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy”. Circulation. vol. 124. 2011. pp. e783-e831. (Newest guidelines on diagnosis and management of patients with HCM.)

Theodos, G, Kapadia, SR. “Hypertrophic cardiomyopathy”. Topol and Teirstein’s Textbook of Interventional Cardiology. 2011. (Comprehensive review of diagnosis and management in HCM.)