Septal reduction therapies in hypertrophic cardiomyopathy: comparison of surgical septal myectomy and alcohol septal ablation

Corresponding Author:

Kyle W Klarich
Cardiovascular Diseases, Mayo Clinic College of Medicine,
Gonda 06, 200 First Street SW, Rochester, MN 55905, USA
Tel: +1 507 284 1226
Fax: +1 507 284 3968
E-mail: klarich.kyle@mayo.edu

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy, defined by cardiac hypertrophy in the absence of an identifiable hemodynamic etiology.

Keywords

alcohol septal ablation, hypertrophic cardiomyopathy, septal myectomy, septal reduction therapy

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy, defined by cardiac hypertrophy in the absence of an identifiable hemodynamic etiology [1,2]. Within HCM, there is a large spectrum of disease, highlighted by heterogeneous genetic underpinnings as well as varied manifestations of myocardial hypertrophy. Clinical presentation is diverse, ranging from asymptomatic to refractory heart failure symptoms or sudden cardiac death (SCD). Left ventricular outflow tract (LVOT) obstruction, either at rest or with physiologic provocation, occurs in approximately 70% of patients with HCM [3]. Left ventricular outflow obstruction is a major cause of exertional symptoms of dyspnea, angina and syncope, and is associated with a poorer prognosis. The majority of patients with obstruction can be managed with medical therapy consisting of β-blockade, verapamil, or disopyramide alone or in combination, as well as avoidance of gradient provocation (decreases in preload or afterload) [4].

There is a subset of patients with obstructive HCM who continue to have severe limiting symptoms despite optimal medical therapy or who are intolerant to medical therapy; at the Mayo Clinic these comprise approximately one third of patients, reflecting our referral practice, with smaller proportions reported elsewhere [5]. In this subset of patients with medically refractory symptoms and significant LVOT obstruction (defined as a gradient of 50 mmHg at rest or with physiologic provocation, associated with septal hypertrophy and systolic anterior motion [SAM] of the mitral valve), septal reduction therapies should be considered. The 2011 ACCF/AHA Guidelines for Diagnosis and Treatment of Hypertrophic Cardiomyopathy recommend septal myectomy at experienced centers (those with an individual operator >20 procedures or a program with >50 procedures, with mortality rates less than 1%, complication rates less than 3% and documented success at symptom relief) as the first consideration for septal reduction therapy (class IIa, level of evidence B) [4]. Alcohol septal infarction, commonly referred to as alcohol septal ablation (ASA), is an alternative to myectomy in selected patients either with contraindication to myectomy, such as excessive surgical risk, or who have a preference for ablation after informed discussion (class IIb, level of evidence B) [4]. Percutaneous intervention has been rapidly adopted, with rates of alcohol septal ablation presently exceeding myectomy at many institutions. The optimal approach to treatment of obstruction remains controversial [5–8].

Pathophysiology of obstruction

Recognition and understanding of the underlying anatomy, mechanism and hemodynamics of LVOT obstruction in HCM is key to any discussion of septal reduction therapies. In HCM, the mitral leaflets are anteriorly positioned with extension of leaflet tips past the point of coaptation into the outflow tract [9]. The papillary muscles are anteriorly malpositioned and can insert directly onto the mitral leaflet. These geometric papillary muscle changes, in combination with mitral leaflet elongation, lead to less posterior leaflet tethering and thus provide sufficient leaflet mobility to result in SAM [10–13].

Studies have demonstrated that given the mitral anatomy in HCM, the predominant mechanism of SAM is related to drag on the mitral valve leaflet, generated by blood flow acceleration across the septum during ventricular systole, ‘pushing’ the leaflets into the LVOT (Figure 1) [14–18]. As opposed to a fixed stenosis in aortic stenosis, subvalvular obstruction is dynamic and fluctuates significantly based upon changes in numerous of clinical factors, including fluctuations in volume status, autonomic nervous activity, diurnal variation, pharmacotherapy, exercise and physical position during assessment [18–22]. Despite the fact that the degree of obstruction is highly dynamic (indeed, fluctuating on a minute-to-minute basis) [20,23–24], it is important to document whether severe obstruction does occur and relate its presence to the patient’s symptoms [25–33].

Nonobstructive hypertrophic cardiomyopathy

Although not the primary focus of this review, it is important to recognize that outflow obstruction is not the only cause of symptoms in patients with HCM. On a cellular basis, HCM is characterized by cardiomyocyte hypertrophy, myofibrillar disarray and interstitial fibrosis [34], with mounting evidence that myocardial ischemia plays a significant role [35]. These cellular changes result in regional and global diastolic dysfunction in essentially all patients with HCM, which in turn is a major contributor to symptoms in both obstructive and nonobstructive HCM [36,37].

Patients with nonobstructive HCM represent approximately one third of all patients with HCM, and prognosis is generally considered favourable [3]. In symptomatic patients with nonobstructive HCM, pharmacotherapy remains the mainstay of treatment. Our practice is use of β-blockade or verapamil in these patients, with selected use of diuretics [38]. Medically refractory patients with nonobstructive HCM remain a therapeutic dilemma and investigations into alternative pharmacotherapies are ongoing [39]. In nonobstructive patients with apical HCM and severe hypertrophy to the point of limiting diastolic left ventricular filling, apical myectomy is a recently emerging option. Apical myectomy improves functional status by decreasing left ventricular end-diastolic pressure, improving operative compliance and increasing stroke volume [40]. The only other option in this highly symptomatic subset of HCM patients is cardiac transplantation. Understanding of when to choose apical myectomy over transplant and which patients receive the most benefit is evolving and few centers offer this intervention at present. The primary indication for myocardial reduction therapy in medically refractory patients remains relief of obstruction.

Septal myectomy

Ever since it was initially described in the 1960s, septal myectomy (muscle excision) has been considered the primary invasive treatment for drug-refractory symptoms in HCM patients with obstructive pathophysiology. Initially performed by Cleland et al. [41], myectomy was subsequently refined to a narrow rectangular trough by Morrow and Brockenbrough (Figure 2A) [42].

The success of myectomy is dependent upon surgical experience; therefore, guidelines recommend it be performed at high-volume referral centers of excellence [4]. Myectomy must be approached in a detail-oriented, systematic fashion. Operative management should be guided by preoperative comprehensive transthoracic echocardiography, performed by an experienced laboratory. This evaluation is crucial to assess structural and hemodynamic features of the disease; septal morphology, level and severity of flow obstruction(s) (including, when necessary, provocative measures such as Valsalva maneuver, amyl nitrite or exercise), presence of true LVOT obstruction with SAM and an open distal cavity as opposed to cavity obliteration, delineation of mitral valve anatomy, as well as the degree and mechanism of mitral regurgitation [2,44–50].

If obstruction is not identified intraoperatively, administration of isoproterenol should be performed, as anesthetic administration alters loading conditions and may mask dynamic obstruction. Our institution has adopted an extended surgical myectomy, as the most common reason for residual obstruction following myectomy is incomplete resection rather than regrowth of myocardium. Extended myectomy is performed with continuation of the initial incision leftward towards the mitral apparatus and apically towards the papillary muscles (Figure 2A, lower right) [51,52]. Dependent upon the septal morphology and level of obstruction, transapical myectomy or a combination of transaortic and transapical myectomy can be employed to ensure adequate myocardial resection [53,54].

Papillary muscle anomalies in HCM can play a critical role in obstruction [55]. In cases of obstruction due to hypertrophied papillary muscles, additional resection around the base of the muscles is performed. Anomalous chordal structures and fibrous attachments to the ventricular septum are divided or excised, but any attachments to the mitral leaflet free edge are left intact, so as to avoid a flail leaflet [56]. Plication of the anterior mitral leaflet in combination with myectomy has been utilized to restrict mitral leaflet motion [57,58]. In our practice, we do not routinely perform mitral plication, given excellent results with isolated extended septal myectomy in the absence of organic mitral pathology.

Determination of adequate resection is based upon direct visual inspection and digital palpation, with postoperative confirmation of obstruction resolution by direct hemodynamic assessment of left ventricular and aortic pressures with isoproterenol and via transesophageal echocardiography.

Alcohol septal ablation

Alcohol septal ablation was first performed by Sigwart in 1994 [59] and has been rapidly adopted as a percutaneous alternative to myectomy without randomized clinical data. Conceptually, ASA is a chemically induced myocardial infarction targeted at the myocardium that is causing flow obstruction (Figure 2B). Patient appeal from ASA largely stems from avoidance of sternotomy, a fact that may significantly affect informed decision-making [6].

As with myectomy, operator experience is pivotal to ASA success; a case volume >50 patients has been shown to be an independent predictor of survival free of severe symptoms [60]. Greater success rates and lower complication rates are seen at experienced centers for a myriad of reasons: selective identification of proper septal perforators, use of small volumes of injected alcohol, understanding intraprocedural predictors of success, as well as progressive adaptation of procedural technique based upon results and complications.

Our approach to ASA includes assessment of septal perforator myocardial distribution via both angiographic contrast (1–2 ml) and echocardiographic contrast injection (Figure 3) [61]. In our laboratory, perflutren protein type A microspheres (OptisonTM, General Electric Company, CT, USA) are utilized for echocardiographic contrast injection, with image acquisition utilizing contrast-optimized presets. Preablation contrast injection allows for determination that the cannulated septal perforator artery supplies the site of SAM septal contact and that infarction will not involve a site distal to septal contact, a papillary muscle, or the right ventricular free wall. Implementation of contrast echocardiography guidance has virtually eliminated apical and lateral wall infarctions in experienced centers [61,62]. Contrast administration assesses the extent of collateral flow, as determined by rapid contrast washout, which may necessitate slower ethanol injection.

Slower alcohol administration and smaller alcohol volume may reduce the incidence of heart block [63], although we routinely place a temporary transvenous pacemaker implantation in all patients undergoing ASA. We typically inject small amounts of alcohol (1–1.5 ml) over a prolonged period of time. Following injection, the catheter is flushed to ensure alcohol is not delivered into the left anterior descending coronary artery.

Comparison of septal reduction therapies

There is a substantial body of literature attempting to compare ASA and myectomy. Olivotto et al. have elegantly outlined the practical issues in designing a randomized controlled trial to compare these interventions (Figure 4) [7]. In order to obtain a trial comparing 600 patients undergoing myectomy to 600 undergoing ASA, 34,000 HCM patients would need be screened, a number nearly ten times our high-volume institution’s cumulative referral practice. Thus, at present the highest level of evidence stems from single-center cohort studies, meta-analyses and registry experiences [64–66].

Mortality

As evidenced by early surgical experiences describing complications of valvular injury, heart block, iatrogenic ventricular septal defect, lack of complete obstruction relief and higher operative mortality, myectomy has a steep learning curve [52]. Some institutions have reported higher complication rates [67,68], with multinational data in less experienced centers showing mortality rates of 14% [69]. It is recommended that each center assess their own statistics and compare with published data from centers of excellence. However, in experienced institutions, such as ours, the risk of death from lone myectomy has been reduced to less than 1% (Figure 5A) [32]. Furthermore, a multiinstitutional analysis of consecutive isolated myectomies in experienced institutions revealed zero deaths in >1500 consecutive patients [5]. More complex surgeries, such as those in patients undergoing myectomy after failed ASA, have been shown to have higher operative risk [70]. Given a surgical experience spanning more than 50 years, long-term efficacy of myectomy is well established [32,71,72].

The majority of existing ASA literature has focused on short-term survival, as the procedure is newer than myectomy [28,74,75–78]. There has been concern raised within the literature that ASA is associated with a higher risk of cardiac death or aborted cardiac death [8]. However, pooled data across eight studies assessing short-term post-procedural mortality has shown no significant difference between ASA and myectomy (Figure 6A) [66]. Furthermore, in recent studies of intermediate- term outcome, post-ablation survival has been demonstrated to be similar to that of an age- and sexmatched US population (Figure 5B) and comparable to myectomy (Figure 5C) at our center [60,73]. These data have been mirrored in other studies [79,80], including a recent study with longer follow-up (mean: 8.4 years) [81]. With regards to cardiac mortality, there has been concern raised regarding increased risk of ventricular arrhythmias following ASA [8] and long-term consequences of adverse remodeling, although data on the latter is lacking. Long-term data with follow-up beyond 10 years is required to assess both the overall mortality and arrhythmia risk.

Regardless of approach, it is important to recognize that this improvement in natural history does not obviate the need for assessment of SCD risk with appropriate defibrillator implantation when dictated by risk factors. It is beyond the scope of this paper to discuss the assessment and we refer interested readers to the ACCF/ ACC Guidelines for Diagnosis and Management of Hypertrophic Cardiomyopathy [4].

Symptom reduction

Given that the indication for septal reduction therapies is medically refractory symptoms, appraisal of symptom improvement following intervention is paramount. There is substantial literature demonstrating improvement in NYHA functional class following myectomy in patients with resting obstruction [52,72] and more recent data reveal similar improvements are seen in patients with latent obstruction [82]. Similarly, there have been a large number of studies supporting symptom relief in ASA [74,83–85].

While myectomy has previously been reported to result in more symptomatic improvement when compared with ASA [76], meta-analysis data have not shown a statistically significant difference between the techniques (Figure 6B), although there was a trend towards less symptoms with myectomy [66]. Our data clearly shows that myectomy in younger patients (<65 years old) results in significantly more freedom from NYHA class III or IV symptoms when compared with ASA [74]. This may be the result of our referral practice, or the meta-analysis data may reflect heterogeneity of operator experience and patient demographics. Regardless, objective measures of exercise capacity improve more with myectomy than with ASA [76,78].

Relief of obstruction

Despite the dynamic nature of LVOT obstruction in HCM, abolishment of gradient post-procedurally is utilized to determine technical success of septal reduction therapies. Post-myectomy, gradient should be determined intraoperatively by direct pressure measurement and by transesophageal echocardiography, as is routinely performed at our institution. Reduction of gradient post-myectomy is immediate given resection of the offending substrate. In ASA, procedural success is determined via a combination of invasive catheter measures and transthoracic echocardiography. Initial gradient reduction post-ablation likely reflects myocardial stunning (lack of contraction) as opposed to true relief of obstruction from reduction in myocardial mass, as evidenced by immediate gradient reduction, a rise in gradient 1–3 days post-procedurally, and subsequent fall in gradient at 3-month follow-up [86,87]. Because of this stunning phenomenon, prediction of lasting hemodynamic results is difficult. Although not published, it has been our experience that if the gradient is >20 mmHg immediately post ablation, then there will be a poor long-term hemodynamic result. Conversely, if the residual gradient immediately following ASA is <20 mmHg, one cannot predict the degree of gradient reduction, as this decrease may relate entirely to stunning.

Both myectomy and ASA have been shown to alleviate LVOT obstruction. Studies consistently report more complete reduction of the gradient with myectomy [75–77,88–89]. Furthermore, this relationship has remained significant in multiple meta-analyses [65,66].

Improvement in diastolic function

Although not the indication for septal reduction therapy, there is evidence that myectomy results in improvement in diastolic function [90,91], improvement in pulmonary hemodynamics [92], reduction in left ventricular mass disproportionate to the amount of myocardium resected [93] and differential strain improvement [94], all implying positive ventricular remodeling. The reported effects of ASA on diastolic dysfunction are heterogeneous. Some studies have demonstrated improvement in parameters of diastolic function following ASA [95–98], while another study showed no significant difference between diastolic assessment following ASA and myectomy when assessed 5 months post-procedurally [99]. At our institution, we have seen variable change in diastolic function, likely reflecting a balance of obstruction relief and intrinsic effect of the infarct itself [100].

Need for pacemaker implantation

Alcohol septal ablation and myectomy result in differing effects on the conduction system because of the anatomic distribution of the bundle branches within the ventricular septum. The first septal perforator supplies the myocardium containing the right bundle, and thus development of a right bundle branch block is the most common electrical change seen post-ASA. In contrast, myectomy involves resection of tissue containing the left bundle, more typically resulting in a new left bundle branch block (Figure 7A) [101]. The anatomic differences in affected tissues are clearly visualized on post-intervention cardiac MRI (Figure 7B). The presence of an existing left bundle branch block significantly increases the risk of complete heart block in ASA, whereas preexisting right bundle branch block predisposes to complete heart block following myectomy.

The frequency of complete heart block necessitating pacemaker implantation following ASA varies widely, from a multicenter trial reporting 8% [103] to rates as high as 33% [101]. Higher rates may in part stem from larger volumes of alcohol injected or early operator experience [63]. At our institution, new permanent pacemaker placement occurs in 17% of patients [60]. Post-ablation patients who undergo permanent pacemaker implantation for iatrogenic complete heart block have a comparable intermediate-term prognosis to other post-ASA patients [104]. In the absence of right bundle branch block, risk of complete heart block necessitating permanent pacemaker in patients undergoing myectomy is <1% [45]. Meta-analysis data demonstrate that ASA carries an increased risk of need for permanent pacemaker implantation relative to myectomy [66]. Patients who require alcohol administration in multiple vessels are more likely to require permanent pacing [63]. Furthermore, given the fact that ASA and myectomy affect different aspects of the conduction system, patients undergoing myectomy following unsuccessful ASA have a significantly higher rate of pacemaker implantation [70].

Arrhythmogenic risk

The clinical importance of post-ablation scar formation has been an area of controversy within HCM literature. While some have proposed that myectomy does not result in scar formation [5], postmortem data show that following ASA, segmental infarction occurs, albeit with histopathologic differences from atherosclerotic coronary occlusion [105]. Importantly, Valeti et al. found essentially no myocardial enhancement on cardiac MRI following myectomy compared with following ASA, which resulted in delayed enhancement quantitated at 8.0 ± 3.0% of left ventricular mass.

Whether localized infarction related to septal reduction predisposes to arrhythmogenic risk and incidence of SCD remains a topic of debate. While some literature reports rates of sudden death following ASA are comparable to patients not undergoing ablation [81,106] or similarly low as post-myectomy [107], other literature raises a significant concern of increased risk of potentially lethal arrhythmias. Ten Cate et al. reported a fivefold increase in cardiac death and aborted sudden cardiac death following ASA compared with myectomy, primarily driven by ventricular arrhythmia [8], and Noseworthy et al. reported post-ASA annual rates of ventricular arrhythmia, cardiac arrest or appropriate ICD therapy at similar rates [108]. At our institution, we have cared for patients who have experienced sustained ventricular tachycardia following ASA. Conversely, we have demonstrated that myectomy is associated with lower than expected risk of SCD [109].

Patient selection

Decision-making and informed consent with regards to choice of septal reduction therapy must include a myriad of factors. In our practice, the “gold standard” of therapy remains myectomy, consistent with guideline recommendations. However, clinical variables, anatomic factors and patient preferences must be considered for each patient as ASA remains a viable and successful therapy in many HCM patients. We have previously published determinants of success for ASA (Table 1) [60]. When pursuing a discussion with patients, we consider each of the following:

Institutional experience

It cannot be overemphasized that regardless of choice of therapy, site experience remains paramount [4,60]. It is clear that operator experience directly affects both morbidity and mortality. In reports from less experienced centers, reported mortality rates can be dramatically higher [110,111], which can skew comparison of septal reduction techniques. In addition, procedural complication rates for both ASA and myectomy from less experienced centers are likely underestimated given lack of published outcomes from these institutions. However, unsuccessful procedure results and complications are apparent in our referral practice [70].

Coexistent valvular or other structural heart disease

The presence of concomitant structural heart disease must be considered when selecting a procedure:

• Patients with primary mitral valve disease (seen in up to 10% of HCM patients), including flail mitral valve necessitating repair, should undergo myectomy;

• Outflow obstruction may have both fixed and dynamic components [112] or be present at multiple levels [113], and these patients should be referred for surgical management;

• Anomalous attachments of papillary muscles may contribute to obstruction and mandate myectomy [55].

Recognition of these anatomic considerations at the time of septal reduction referral is crucial.

Septal perforator anatomy

There is significant variability in septal perforator anatomy [114]. ASA procedural success is constrained by identification of an appropriate therapeutic target (Figure 8). Use of angiographic and echocardiographic contrast, as outlined above, allows for evaluation of candidate vessels when considering ASA. Even in patients deemed appropriate for ASA, septal perforators have been shown to supply extra-septal anatomy in >25% [115], which may necessitate superselective approaches to branch vessels [116]. A larger left anterior descending dimension (>4.0 cm) is associated with poorer outcome in ASA [60].

Coronary artery disease

Significant coronary artery disease may preclude ASA. In the presence of hemodynamically significant obstructive coronary disease, concomitant coronary revascularization and septal reduction therapy may be warranted. Simultaneous myectomy and coronary artery bypass grafting have been demonstrated to have excellent results [117] and the presence of significant coronary atherosclerotic disease should prompt surgical consideration.

Patient age

Myectomy provides much greater symptom reduction in younger patients (<65 years old) when compared with ASA [74] and benefits of myectomy have been proven even in pediatric populations [91,118–119]. There is a greater body of evidence supporting longterm improvement in hemodynamics and symptoms in myectomy. Additionally, hemodynamic success with septal ablation is more likely achieved in older patients [60]. Therefore, in younger populations (those <65 years of age) we recommend myectomy, whereas in more elderly patients, ASA is considered.

Underlying conduction disease

Preexistent left bundle branch block increases the risk of permanent pacemaker need in ASA and should prompt consideration of myectomy. Conversely, preexistent right bundle branch block is associated with post-myectomy complete heart block and may alter therapy decision-making. In patients with normal conduction, ASA does pose higher risk of complete heart block, necessitating pacemaker implantation.

Resting gradient

Lower LVOT gradient is a predictor of success in ASA [60], whereas symptomatic success in myectomy appears to be independent of preoperative gradient [45]. In patients with resting gradients >100 mmHg, myectomy should be considered.

Septal thickness & morphology

Myectomy is preferred in patients with more severe septal hypertrophy. Myectomy allows individual tailoring of the degree of myocardium resected. The presence of asymmetric hypertrophy has been associated with better outcome [45]. In comparing a series of patients undergoing ASA, patients with septal thickness <18 mm at the site of SAM–septal contact were more likely to achieve hemodynamic success [60]. In cases of midventricular obstruction or apical HCM, septal vascular anatomy may not allow for isolation of target myocardium.

Sudden death risk

While our data do not show increased risk of SCD following ASA [73], ICD registry data is concerning [108]. Our data does suggest that myectomy may favorably alter risk [109]. As such, we presently do not advise decision- making be altered by consideration of this factor.

We continue to recommend defibrillator implantation based upon established guidelines [4], irrespective of septal reduction therapy.

Frailty & operative risk

Determination of operative risk is critical when ascertaining appropriateness for myectomy. In patients with prohibitive surgical risk, contraindications to circulatory bypass or those who are deemed too frail for surgery, ASA is a reasonable alternative to myectomy.

Patient preference

Although many risks and outcomes are equal in metaanalysis, patients often perceive alcohol septal ablation as favorable or lower risk given a percutaneous approach as opposed to sternotomy. Patient preference should be considered after an informed discussion weighing the risks and benefits of each procedure. At the Mayo Clinic, we still have a 5:1 ratio of myectomy to ablation after discussing all risks and benefits.

Conclusion

Septal reduction therapy in the form of ASA or myectomy remains the treatment of choice in HCM patients with obstructive physiology and medically refractory symptoms. Both myectomy and ASA should be performed at referral centers of excellence. Myectomy is an established technique with decades of experience that remains the ‘gold standard’ for septal reduction therapy, with greater LVOT gradient reduction and reduced need for permanent pacemaker implantation. In experienced centers, ASA has similar short-term mortality when compared with myectomy. Clinical characteristics, anatomic features and patient preference should be considered when determining the optimal technique for septal reduction.

Future perspective

Septal myectomy and ASA will remain effective therapies to reduce LVOT gradient and improve symptoms. Given that a randomized trial comparing these techniques is unlikely, future data will continue to be reliant upon cohort studies and meta-analyses. There is a need for further investigation and recognition of ‘real-world’ complication rates from septal reduction therapies performed at lower volume institutions. These data will further underscore the need for myectomy and ASA to be performed at centers of excellence. Additional data are needed with regards to long-term follow-up and arrhythmogenic risk of ASA.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Excecutive summary

Controversy of myectomy versus alcohol septal ablation

• Guidelines recommend myectomy as the ‘gold standard’ for symptomatic, medically refractory hypertrophic cardiomyopathy (HCM) patients with left ventricular outflow tract (LVOT) obstruction, but there remains significant controversy with regards to choice of myectomy or ablation.

• Both septal myectomy and alcohol septal ablation (ASA) have been shown to reduce the LVOT gradient and improve symptoms.

Septal myectomy

• With more than a half-century of experience, the long-term results of myectomy are well-established.

• Success of myectomy is dependent upon surgical experience; in experienced centers, myectomy carries low operative mortality and results in excellent reduction of LVOT gradient, symptomatic improvement and longterm postoperative survival similar to the general population.

Alcohol septal ablation

• ASA is a newer technique than myectomy, with favorable intermediate-term prognosis but unknown longterm results.

• As with myectomy, the success of ASA is experience dependent and referral centers of excellence are crucial.

Comparison of septal reduction therapies

• Limitations to study enrollment preclude a randomized controlled trial comparing myectomy and ASA.

• In experienced centers, intermediate-term mortality following ASA and myectomy is comparable, but longterm results are uncertain.

• Both ASA and myectomy result in symptom reduction, although myectomy is more efficacious in patients <65 years of age.

• Myectomy consistently results in more gradient reduction compared with ASA.

• There is debate regarding arrhythmogenic risk related to post-ASA scar, with long-term results unknown.

Patient selection

• Institutional experience is critical for both myectomy and ASA.

• Coexistent primary valvular (including mitral valve disease other than SAM) or other structural heart disease mandates surgical myectomy.

• Septal perforator anatomy and coronary artery disease may preclude ASA.

• Younger patients (age <65 years) achieve greater symptom reduction and more hemodynamic improvement with myectomy.

• In patients with higher resting gradients (>100 mmHg) or greater septal thickness (>18 mm), myectomy is more efficacious.

• Operative risk and informed patient preference should be considered when choosing between ASA and myectomy.

References

Papers of special note have been highlighted as:

• of interest; •• of considerable interest

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