INTRODUCTION — Hypertrophic cardiomyopathy (HCM) is a genetically determined heart muscle disease most often (60 to 70 percent) caused by mutations in one of several sarcomere genes which encode components of the contractile apparatus. (See "Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing".)
HCM is characterized by left ventricular hypertrophy of various morphologies, with a wide array of clinical manifestations and hemodynamic abnormalities (figure 1). Depending in part upon the site and extent of cardiac hypertrophy, HCM patients can develop one or more of the following abnormalities:
●LV outflow obstruction (see "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction")
●Diastolic dysfunction
●Myocardial ischemia
●Mitral regurgitation
These structural and functional abnormalities can produce a variety of symptoms, including:
●Fatigue
●Dyspnea
●Chest pain
●Palpitations
●Presyncope or syncope
In broad terms, the symptoms related to HCM can be categorized as those related to heart failure (HF), chest pain, or arrhythmias. Patients with HCM have an increased incidence of both supraventricular and ventricular arrhythmias and are at an increased risk for sudden cardiac death (SCD). (See "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation" and "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk".)
A resting or exercise provoked left ventricular outflow tract (LVOT) gradient is present in most patients with HCM (70 percent) [1]. Significant LVOT obstruction at rest, present in 20 to 30 percent, is an independent predictor of poor prognosis, particularly development of limiting HF symptoms [2]. Four major approaches are available for treatment of LVOT obstruction in patients with HCM (algorithm 1):
●Pharmacologic therapy
●Septal myectomy
●Alcohol (ethanol) septal ablation
●Dual chamber pacing (which has only a limited role)
The nonpharmacologic treatment of patients with HCM will be reviewed here. Other issues such as the clinical manifestations, natural history, management of arrhythmias, and medical therapy of this disorder are discussed separately. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation" and "Hypertrophic cardiomyopathy: Natural history and prognosis" and "Hypertrophic cardiomyopathy in adults: Supraventricular tachycardias including atrial fibrillation" and "Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk" and "Hypertrophic cardiomyopathy: Medical therapy for heart failure".)
MECHANISM OF LV OUTFLOW TRACT OBSTRUCTION — Left ventricular outflow tract (LVOT) obstruction in HCM is due to systolic anterior motion (SAM) of the mitral valve (usually the anterior leaflet) contacting the ventricular septum (SAM-septal contact), resulting in mechanical impedance to blood flow and the generation of a pressure gradient between the LV and the aorta during mid-systole. Systolic anterior motion of the mitral valve is caused by high LVOT blood velocities that pull the anterior mitral valve leaflet toward the ventricular septum (Venturi or drag effect). In addition, as the anterior mitral valve leaflet is displaced toward the septum, a gap may form between both mitral valve leaflets, which results in posteriorly directed mitral regurgitation. The goal of therapy of LVOT obstruction in HCM is to reverse or reduce the pathophysiologic factors responsible for obstruction. (See "Hypertrophic cardiomyopathy: Morphologic variants and the pathophysiology of left ventricular outflow tract obstruction", section on 'Pathophysiology and evolution of LVOT obstruction'.)
TREATMENT OPTIONS FOR LVOT OBSTRUCTION — Left ventricular outflow tract (LVOT) obstruction is a strong, independent predictor of HF symptoms and the most important determinant of limiting symptoms in patients with HCM. Management strategies attempt to increase LV chamber size or decrease cardiac inotropy, thereby diminishing systolic anterior motion (SAM)-septal contact, resulting in a reduced or abolished LVOT gradient. Both pharmacologic and nonpharmacologic therapy options exist to treat symptomatic LVOT obstruction in patients with HCM.
Pharmacologic therapy is the first-line approach in patients with HCM and symptomatic LVOT obstruction (algorithm 1) [3]. If significant HF symptoms (New York Heart Association [NYHA] class III/IV) (table 1) persist despite maximal medical therapy, or patients have recurrent syncope judged to be related to hemodynamic compromise from LVOT obstruction, and an LVOT gradient ≥50 mmHg is present at rest or with provocation, patients may be candidates for either surgical myectomy or alcohol septal ablation. An invasive septal reduction therapy is required in approximately 5 percent of all patients with HCM and up to 30 percent in tertiary referral populations [4].
Dual chamber pacing can be tried in some patients, but this is now primarily performed in patients who have a dual chamber ICD implantation for other indications or in patients who are not candidates for or do not want to pursue invasive septal reduction therapies. (See 'Pacemaker therapy' below.)
Pharmacologic therapy for LVOT obstruction — Pharmacologic therapy is the first-line approach in patients with HCM and symptomatic LVOT obstruction [5,6]. The approach to pharmacologic therapy in such patients is discussed separately. (See "Hypertrophic cardiomyopathy: Medical therapy for heart failure".)
Surgical septal myectomy — Surgical septal myectomy relieves LVOT obstruction by direct removal of septal muscle. In addition, abnormalities of the mitral valve and papillary muscles can be addressed at the time of septal myectomy.
Myectomy procedure — For surgical septal myectomy, a sternotomy is performed, and the patient is placed on cardiopulmonary bypass. Following this, an aortotomy is performed and the proximal septum is approached through the aortic valve. Approximately 3 to 15 g of ventricular septal muscle are excised and removed in order to widen out the LV outflow tract area [7-14].
The contemporary procedure usually involves a distal extension of the myectomy trough to the base of the papillary muscles along with inspection and, if needed, revision of mitral valve leaflets and chordal structures. Extending the myectomy trough allows for release (or realignment) of anterolateral papillary muscle, which is often apically displaced (and frequently fused to the LV wall) and as a result tethers the plane of the mitral valve toward the basal septum. The combination of myectomy trough and anterolateral papillary muscle release usually results in widening of the LVOT area, elimination of Venturi forces, complete reduction of the LVOT gradient, and substantial decrease in the degree of mitral regurgitation.
Multiple groups have shown this contemporary myectomy procedure to be effective in patients with significant LVOT obstruction with relatively lesser amounts of basal septal hypertrophy, in whom a significant number of patients required mitral valve and papillary muscle intervention as part of the procedure [15-18]. In the largest cohort of 1486 patients who underwent myectomy at Mayo Clinic between 2005 and 2014, which included 369 patients with maximal septal thickness <18 mm, 612 patients with maximal septal thickness 18 to 21 mm, and 505 with maximal septal thickness >21 mm, there was no significant difference in postoperative LVOT gradient reduction or need for additional mitral valve procedures based upon preoperative maximal septal thickness [18].
An apical approach may be performed in a very small number of patients in whom there is substantial hypertrophy in the distal portion of the LV cavity; this procedure is intended to enlarge the LV cavity for better LV filling and a resultant improvement in stroke volume [19,20].
Transesophageal echocardiography (TEE) is vital in intraoperative assessment of septal morphology and thickness, as well as for defining mitral valve and subvalvular anatomy prior to beginning surgery and to judge efficacy of the operation when complete. Due to changes in hemodynamics following the induction of anesthesia, resting intraoperative TEE-derived LVOT gradients are often significantly lower than preoperative LVOT gradients derived from transthoracic echocardiography, although provocation with either isoproterenol or dobutamine can reliably reproduce increased LVOT gradients [21]. In addition, intraoperative TEE can evaluate for significant mitral regurgitation due to intrinsic mitral valve disease (not SAM-related) that may require surgical repair, as well as decision to perform adjunctive mitral valve plication (ie, shortening) in patients with particularly elongated anterior mitral valve leaflets to ensure optimal relief of SAM. Intraoperative TEE can also identify abnormalities of the subvalvular area that may be contributing to LVOT obstruction, including anomalous anterolateral papillary muscle insertion directly into anterior leaflet of mitral valve in absence of chordae tendinea, which if present may alter surgical strategy. Following the myectomy procedure, intraoperative TEE assessment of LVOT gradients is important to ensure that LVOT obstruction is as optimally treated as possible, as well as to assess for residual mitral regurgitation and to ensure that complications such as ventricular septal defect are not present [22,23]. Among a cohort of 293 patients who underwent myectomy, 63 patients (22 percent) had no resting LVOT obstruction but did have provocable LVOT obstruction with isoproterenol or dobutamine on TEE immediately postoperatively, resulting in additional myocardial muscle removal in 41 of 63 patients [21]. This suggests a role for routine provocative testing in all patients without LVOT gradient under basal conditions, prior to leaving the operating room to guide the surgeon in obtaining the optimal surgical result.
Mitral valve intervention — Mitral valve repair is occasionally performed at the time of septal myectomy, predominantly in patients with elongated leaflets or mitral regurgitation caused by primary mitral valve disease [24-27]. However, mitral valve replacement as the primary method of relieving obstruction is now infrequently performed, given the improvements in symptoms and LVOT gradient following septal myectomy in nearly all patients [28-33]. In a series of 1134 patient who underwent septal myectomy at the Mayo Clinic between 1961 and 2007, only nine patients (1 percent) underwent mitral valve replacement without myectomy [31].
For patients with HCM and refractory HF symptoms related to LVOT obstruction and who are not candidates for a septal reduction therapy, percutaneous mitral valve plication may be effective in reducing the LVOT gradient and relieving HF symptoms. In a cohort of six patients who underwent mitral valve plication using the MitraClip device (which was successfully implanted in five patients, with the procedure aborted in one patient due to the development of cardiac tamponade), there was significant immediate improvement in the LVOT gradient (from 91 to 12 mmHg), mitral regurgitation grade (from 3 to 0.8), and cardiac output (from 3 liters/minute to 4.3 liters/minute) following the procedure [34]. Moderate mitral stenosis was documented in two patients immediately following mitral valve plication. Over an average follow-up of 15 months, there was significant improvement in symptoms, with all patients achieving NYHA class I or II functional status. However, three patients were noted on long-term follow-up to have increased LVOT velocities without documented systolic anterior motion of the mitral valve, a finding of unclear significance that needs additional investigation. Additional data and longer-term follow-up are required to better assess the efficacy, safety, and proper patient selection for mitral valve plication in patients with obstructive HCM and refractory symptomatic LVOT obstruction.
Neither primary mitral valve replacement nor mitral valve plication should be performed for relief of LVOT obstruction if septal reduction therapy is an option [5].
Complications of septal myectomy — Complications of myectomy include:
●Excessive removal of muscle can cause a ventricular septal defect (2 percent risk), a serious complication that may be more common in patients with only a mildly hypertrophied (relatively thin) septum [11,35,36]. Intraoperative echocardiography can assist in avoiding this complication and should be used for monitoring in all cases [22].
●Complete heart block (CHB) requiring a permanent pacemaker occurs postoperatively in 5 percent or less of patients [11,37-39], while a substantial number of patients develop a left bundle branch block (LBBB) after surgery [39,40]. Among 2482 consecutive patients who underwent septal myectomy at a single center between 1961 and 2016, including 2159 patients (87 percent) with normal baseline pre-operative conduction, 39 percent developed LBBB, 1 percent developed RBBB, and 0.6 percent developed CHB post-myectomy [41]. However, among 112 patients with baseline RBBB, 39 patients (35 percent) developed CHB post-myectomy. Thus, patients with right bundle branch block at baseline are at markedly increased risk for CHB [39,41].
●Very rarely, traction on the aortic valve to improve visualization of and access to the interventricular septum may cause aortic regurgitation that may necessitate subsequent aortic valve replacement. In most cases, the degree of aortic regurgitation after myectomy is minimal [42].
Perioperative mortality — Studies of septal myectomy performed through the mid-1990s described in-hospital mortality rates of 4 to 6 percent, with higher rates in patients over 65 years of age [13,14,43]. However, operative mortality from subsequent series performed at experienced centers using contemporary surgical methods is now 1 to 2 percent or less [35,37,44-47]. As examples:
●In a series of 338 patients from Toronto General Hospital between 1978 and 2002, the operative mortality rate after surgical myectomy dropped from 2.1 percent (four deaths) in the first 193 patients (between 1978 and 2002) to 0.7 percent (one death) in the last 145 patients (between 1993 and 2002) [37].
●In a series of 298 consecutive patients undergoing isolated septal myectomy at Mayo Clinic between 2011 and 2014, 30-day mortality was zero, with 98.7 percent survival at six years [47].
Patients undergoing more complicated surgery (eg, concurrent valve replacement or coronary artery bypass graft surgery) have a higher mortality rate [35,37]. In the series from Toronto General Hospital, the 30-day mortality rate was 3.4 percent (three deaths) in the 89 patients who had any concomitant surgical procedure compared with 0.8 percent in 249 patients who underwent myectomy alone [37].
Long-term outcomes — Myectomy results in resolution of the LVOT gradient and improvement in HF symptoms in almost all patients, reductions in implantable cardioverter-defibrillator (ICD) discharges, improvement in left atrial volumes and pulmonary hypertension, and is associated with excellent long term survival [37,40,44,45,48-52].
●In a series of 338 patients from Toronto General Hospital, 72 percent of patients had NYHA class III or IV symptoms (table 1) at baseline; after myectomy, 83 percent of patients improved to NYHA class I or II, and 98 percent had no resting LVOT gradient (mean preoperative value 66 mmHg) [37]. Similarly, in studies from the Cleveland Clinic and the Mayo Clinic, the mean LVOT gradient decreased from 67 mmHg pre-myectomy to 7 mmHg post-myectomy, and the NYHA class improved from 3.3 before surgery to 1.5 after surgery [40,45]. In a systematic review of 16 septal myectomy cohorts (2791 patients), the average reduction in LVOT gradient was 77 percent following septal myectomy [53].
●A retrospective analysis from a single center found that HCM patients who had undergone septal myectomy had a lower rate of appropriate ICD discharges as compared with a non-myectomy HCM group [48].
●A retrospective analysis of 306 consecutive patients from a single center who underwent septal myectomy found significant improvements in all patients with pre-operative pulmonary hypertension (right ventricular systolic pressure ≥35 mmHg), with the greatest improvements seen in patients with moderate or severe pulmonary hypertension (right ventricular systolic pressure ≥50 mmHg) [54]. A separate analysis showed significant reduction in left atrial volume index following surgical myectomy [55], but this finding was not noted in the older Toronto series [37].
●Among a cohort of 503 patients who underwent septal myectomy at a single center between 2004 and 2017, 480 patients (96 percent) had long-term sustained improvement to NYHA class I or II [46]. A small minority (4 percent) experienced persistent advanced NYHA class III/IV symptoms despite relief of the LVOT gradient. Nonresponders to myectomy often had significant medical comorbidities contributing to persistent symptoms. Although a substantial number of HCM patients with massive LV hypertrophy ≥30 mm achieved clinical improvement with myectomy, massive septal hypertrophy was the only predictor of failure to respond to surgical relief of obstruction. These data support the management principle that surgical myectomy is associated with substantial improvement in HF symptoms in the vast majority of HCM patients, but significant benefit is not inevitable.
Long-term survival is excellent after septal myectomy performed at experienced centers.
●In a series of 1337 patients with HCM treated at the Mayo Clinic between 1983 and 2001, survival after septal myectomy was 98, 96, and 83 percent at 1, 5, and 10 years [45]. These values did not differ from those in patients with nonobstructive HCM or matched controls in the general population but were significantly higher than in a group of 228 patients with obstructive HCM who were managed medically in whom the survival rate was 90, 79, and 61 percent. In another series from the Mayo Clinic group which included 2482 patients who underwent septal myectomy between 1961 and 2016, patients who developed CHB post-operatively requiring permanent pacing had significantly higher mortality risk (HR 1.57; 95% CI 1.2-2.1) [41].
●Virtually identical values (98, 95, and 83 percent at 1, 5, and 10 years) were noted in the series of 338 patients from the Toronto General Hospital [37]. There were five independent predictors of overall mortality: concomitant CABG, preoperative history of atrial fibrillation, preoperative left atrial diameter ≥46 mm, age ≥50 years, and female gender.
Alcohol (ethanol) septal ablation — Alcohol septal ablation relieves LVOT obstruction by creating a localized myocardial infarction in the area of the basal septal muscle where SAM-septal contact is occurring. Following remodeling of this area, the LVOT is widened, thereby relieving LVOT obstruction. However, in contrast to treatment with surgical septal myectomy, abnormalities of the mitral valve and its papillary muscles cannot be addressed at the time of alcohol septal ablation.
Ablation procedure — Percutaneous transluminal septal myocardial ablation (also referred to variously as alcohol [ethanol] septal ablation, transcoronary ablation of septal hypertrophy, and nonsurgical septal reduction therapy) is performed as part of a cardiac catheterization. The procedure consists of accessing the first or second septal perforator coronary artery branch and injecting ethanol for medical use to create a controlled, localized myocardial infarction in the area of the basal septum, which over time will result in remodeling of this area and widening of the LVOT with reduction in the obstruction caused by SAM-septal contact (figure 2 and waveform 1 and image 1) [56-60]. The myocardial scar produced with alcohol septal ablation is often large, occupying on average 10 percent of the total LV mass [61].
Myocardial contrast echocardiography (MCE) can accurately delineate the size of the septal vascular territory and can predict the infarct size that will result from ethanol infusion [62]. In one series of patients treated with alcohol ablation, the use of MCE was associated with a higher rate of acute (92 versus 70 percent) and mid-term (94 versus 64 percent) procedural success than patients in whom MCE was not used [58]. MCE also may lower the rate of complete heart block requiring pacemaker implantation [44]. (See "Contrast echocardiography: Clinical applications" and 'Complete heart block' below.)
Benefit — Alcohol septal ablation reduces LVOT obstruction, improves symptoms, increases exercise capacity, and may improve long-term survival. The benefit of alcohol septal ablation is comparable in younger and older (age ≥60 years) patients [63]. The following findings from a 2006 meta-analysis of 42 observational studies (2959 patients, mean age 54) with mean follow-up of 13 months illustrate a range of results for alcohol septal ablation [64]:
●The resting LVOT gradient had decreased from 65 mmHg to 15 mmHg, while the provoked LVOT gradient had decreased from 125 mmHg to 31 mmHg.
●The NYHA class improved from a mean of 2.9 to 1.2 (table 1), peak oxygen consumption increased from 18 to 24 mL/kg/min, and mean exercise capacity increased from 325 to 438 seconds.
●Repeat alcohol septal ablation, due to incomplete reduction of outflow gradients from initial procedure, was required in 6.6 percent of patients.
In a 2015 systematic review and meta-analysis of 11 cohorts (2013 patients) who underwent alcohol septal ablation and were followed for an average of 6.2 years, the average reduction in LVOT gradient post-ablation was 71 percent, and only 7.7 percent of patients ultimately required repeat intervention [53]. In the largest published cohort of 1275 patients with HCM (mean age 58 years, median follow-up 5.7 years) who underwent alcohol septal ablation at one of seven European sites between 1996 and 2015, 30-day mortality was only 1 percent, with significant reductions in LVOT gradient (67 to 16 mmHg) and functional status (mean NYHA class 2.9 to 1.6) following the ablation [65].
Individual observational studies suggested benefit in certain subsets of patients [66-68]:
●There are conflicting data regarding the efficacy of alcohol septal ablation in patients with a markedly thickened septum [65,68-70].
•In the largest reported cohort of 531 patients who underwent alcohol septal ablation in one of five European centers between 1996 and 2010, patients had marked improvements in symptoms regardless of the baseline septal thickness [68]. However, survival was significantly worse for patients with baseline septal thickness of ≥25 mm (hazard ratio [HR] 5.0 compared with baseline septal thickness <20 mm; 95% CI 2.1-12). Similarly, among 1519 patients from the Euro-ASA registry who underwent alcohol septal ablation between 1997 and 2018 and were followed for 5.4 years, including 67 patients with baseline septal thickness ≥30 mm, most patients had marked improvements in symptoms and LVOT gradient, although all-cause mortality was slightly higher among patients with baseline septal thickness ≥30 mm (2.9 versus 2.6 per 100 person-years) [71].
•In a single-center study of 102 consecutive patients undergoing alcohol septal ablation for symptomatic LVOT obstruction, in which 73 patients (72 percent) had significant improvement following alcohol septal ablation (defined in this study as at least a 50 percent reduction in LVOT gradient at six months post-ablation), patients who responded had lesser amounts of septal hypertrophy (mean septal thickness 22.6 mm compared with 28.2 mm in nonresponders) [69].
●Among a multi-center cohort of 1505 patients who underwent alcohol septal ablation, from which propensity scoring was used to match 172 pairs with septal thickness ≤16 mm or >16 mm, there was no difference in 30-day mortality based on maximal septal thickness [70]. Long-term survival was better in patients with septal thickness ≤16 mm, although this group experienced more frequent early complications (primarily the need for pacemaker implantation).
●Alcohol septal ablation appears beneficial in patients with no rest gradient but a provocable gradient of ≥30 mmHg. In a report of 45 such patients, the provocable gradient fell from 111 to 24 mmHg and NYHA class improved from 3.1 to 1.7; these changes were similar to those in HCM patients with resting obstruction [66].
●Some patients who do not show initial benefit can have later improvement. This was illustrated in a series of 47 patients with a mean baseline LVOT gradient of 98 mmHg who underwent alcohol septal ablation [67]. All patients were followed with serial echocardiograms at three days, three months, and one year after the procedure. Among 22 patients who had no significant reduction in the LVOT gradient three days after the procedure, 16 had a significant improvement at three months. These late responders had a similar LVOT gradient at one year compared with those who improved immediately after the procedure (27 versus 13 mmHg, respectively).
Long-term survival following alcohol septal ablation appears reasonable and approaches that of the general population [64,72,73]. In the meta-analysis of 42 observational studies noted above, one-year mortality following alcohol septal ablation was 2 percent [64]. In a cohort of 952 patients (mean age 55.7 years; 73 percent with NYHA class III or IV symptoms) who underwent alcohol septal ablation between 2000 and 2017 and were followed up for an average of six years, survival at 5, 10, and 15 years was 96, 88, and 80 percent, respectively [73].
Complications of alcohol septal ablation — Complications of alcohol septal ablation in patients with HCM include:
●Coronary artery dissection
●Pericardial effusion
●Large myocardial infarction resulting from escape of ethanol from the target vessel to another coronary vessel (usually the left anterior descending artery)
●Complete heart block
●Ventricular tachyarrhythmias
●Arrhythmic death
The frequency of short to intermediate term complications was evaluated in the meta-analysis of 42 studies of 2959 patients undergoing alcohol septal ablation at a mean follow-up of 13 months [64]. The mean 30 day mortality rate was 1.5 percent, and mean mortality beyond 30 days was 0.5 percent. Other complications included:
●Ventricular fibrillation (2.2 percent)
●Left anterior descending artery dissection (1.8 percent)
●Pericardial effusion (0.6 percent)
●Complete heart block (10.5 percent)
A subsequent study on long-term effects of alcohol septal ablation has demonstrated that out to a mean follow-up of five years, patients had a similar survival compared with the general population and with HCM patients undergoing surgical myectomy [74].
Also, because of the potential risk for creating a ventricular septal defect, alcohol septal ablation should not be performed in patients with basal septal wall thickness of ≤15 mm [5].
Complete heart block — Complete heart block (CHB) requiring a pacemaker occurs in approximately 8 to 10 percent of patients after alcohol ablation [53,64,73]. In a report of 261 consecutive patients, significant predictors for this complication on multivariate analysis included LBBB or first degree AV block on baseline ECG prior to the procedure, injection of ethanol by bolus rather than infusion, lack of use of myocardial contrast echocardiography, injection of more than one septal artery, and female sex [75].
In contrast to septal myectomy, injury to the right bundle branch is much more common with alcohol ablation (54 versus 6 percent in one report) [61,76], probably because the right bundle branch and the left anterior fascicle are usually supplied by septal branches of the left anterior descending artery [39,40,76]. The predilection for involvement of the right bundle branch explains why LBBB at baseline is the strongest predictor for developing CHB after the procedure necessitating pacemaker placement [75]. (See 'Complications of septal myectomy' above.)
Transient conduction abnormalities are likely due to the acute effects of alcohol on the myocardium and conduction system (eg, ischemia, edema, and inflammation), while permanent conduction abnormalities reflect necrosis, scarring, and possibly remodeling. The use of myocardial contrast echocardiography and slow ethanol injection was associated with a lower rate of complete heart block (8 versus 22 percent) [44].
Based upon the above observations, some have suggested continuing temporary pacing for ≥48 hours after alcohol ablation or for ≥48 hours after the resolution of transient CHB [76]. Continuation of temporary pacing up to six days after alcohol ablation has been suggested for patients with retrograde atrioventricular block and at least one additional risk factor as defined above [77].
Patients who develop CHB following alcohol septal ablation appear to have a similar benefit from the procedure as those who do not develop CHB. With the exception of the requirement for pacemaker insertion, the clinical and echocardiographic outcomes for patients who developed CHB in the above series of 261 patients were not different from those without CHB, with comparable improvements in NYHA class and exercise time and comparable reductions in septal thickness and the LVOT gradient [75]. (See 'Benefit' above.)
Sudden cardiac death — While reentrant ventricular tachyarrhythmias may be caused by the myocardial scar resulting from alcohol septal ablation, the totality of longitudinal follow-up data demonstrate that risk for SCD is not significantly increased.
●In a nonrandomized study of 1047 consecutive patients with HCM from three tertiary referral centers (690 with LVOT obstruction and gradient ≥30 mmHg, of whom 316 underwent alcohol septal ablation and 250 underwent septal myectomy) who were followed for an average of 7.6 years, sudden cardiac death was lower in patients treated with septal myectomy (0.8 percent per year) compared with both alcohol septal ablation (1.0 percent per year; adjusted HR 2.1; 95% CI 1.0-4.4) and medical therapy (adjusted HR 2.3; 95% CI 1.0-5.2) [78].
●Results from the multicenter ICD study in patients with HCM demonstrated a three- to fourfold increased risk of appropriate ICD shocks for ventricular tachycardia in patients who had undergone alcohol septal ablation compared with other patients with HCM in the registry [79].
Conversely, a number of meta-analyses and single-center experiences with moderate duration follow-up (up to a mean of five years after procedure) have noted no increased risk of sudden death among alcohol septal ablation patients [53,73,74,80-82]. In a 2015 meta-analysis which pooled data from 27 cohorts (2013 patients underwent alcohol septal ablation, 2791 underwent surgical septal myectomy), there was no significant difference in long-term mortality, functional status, or ventricular arrhythmias [53].
There is no definitive evidence that alcohol septal ablation increases the risk of sudden cardiac death. However, clarifying this issue more precisely will require the completion of studies with longer follow-up time with larger cohorts of patients who have undergone alcohol ablation.
Comparison of septal myectomy and alcohol septal ablation — Septal myectomy and alcohol septal ablation are both performed in clinical practice. Randomized trials comparing the two approaches have not been performed and are unlikely to ever occur. However, several observational studies, as well as a systemic review and meta-analysis, have compared the relative safety and efficacy of these procedures [53].
Anatomic results — The acute morphological changes from septal myectomy and alcohol septal ablation were compared in a prospective study of 48 patients using serial cardiac magnetic resonance (CMR) imaging [61]. Patients with left ventricular outflow tract (LVOT) gradients ≥50 mmHg and NYHA class III to IV symptoms were offered surgical septal myectomy as primary treatment, with alcohol septal ablation offered as an alternative. Twenty-four patients underwent each procedure. The following findings were noted:
●Patients treated with septal ablation were older than those treated with myectomy (62 versus 50 years), but otherwise there were no significant differences in baseline characteristics between the two groups.
●Surgical septal myectomy consistently resulted in resection of the obstructing portion of the anterior basal septum. There was no evidence of myocardial necrosis.
●The results were more variable in patients treated with alcohol septal ablation. In 75 percent of patients, there was transmural necrosis of the inferior basal septum. In 25 percent of patients, there was sparing of the proximal basal septum with nontransmural necrosis in the distal basal septum and residual gradients at follow-up.
Observations from a number of studies suggest that the effectiveness of reducing LVOT gradients with alcohol septal ablation in HCM patients with massive LV hypertrophy (>30 mm) is uncertain and is therefore discouraged (ie, surgical myectomy should be considered in these patients) [83]. In addition, septal myectomy results in significantly lower residual LVOT gradients, although the impact of this difference in LVOT gradients on symptoms appears to be minimal [84].
Clinical outcomes — Both septal myectomy and alcohol septal ablation reduce LVOT obstruction and improve NYHA class in HCM although complications and some outcomes differ [53,74,78,84-87]. In general, there is no significant difference in long-term survival following either procedure, although all the data on outcomes are from nonrandomized trials.
●In a 2015 systematic review and meta-analysis of 4804 patients from 27 nonrandomized cohorts with long-term follow-up (2791 patients from 16 septal myectomy cohorts [median age 47 years; mean follow-up 7.4 years] and 2013 patients from 11 alcohol septal ablation cohorts [median age 56 years; mean follow-up 6.2 years]), the following findings were noted [53]:
•No significant difference in long-term mortality (1.5 percent per year for septal myectomy versus 1.4 percent per year for alcohol septal ablation).
•No significant difference in rates of aborted sudden cardiac death (0.4 percent per year for septal myectomy versus 0.5 percent per year for alcohol septal ablation).
•The need for permanent pacemaker implantation and reintervention were significantly lower following septal myectomy compared with alcohol septal ablation (4.4 versus 10 percent for pacemaker and 1.6 versus 7.7 percent for reintervention, respectively).
●Subsequent to the meta-analysis, investigators from a tertiary United States referral center published their contemporary experience with 477 consecutive patients with HCM and medically-refractory LVOT obstruction undergoing septal reduction therapy (septal myectomy in 378, alcohol septal ablation in 99), with each procedure performed by a single experienced operator [87]. There was no significant difference in procedure-related mortality between the two groups (three deaths following septal myectomy, none following alcohol septal ablation). Over an average follow-up of four years, there was no significant difference in long-term mortality (2.9 versus 2 percent in the septal myectomy and alcohol septal ablation groups respectively), and 95 percent of patients reported improvement in HF symptoms to NYHA class I/II (96 versus 90 percent in the septal myectomy and alcohol septal ablation groups respectively).
●In a nonrandomized study of 1047 consecutive patients with HCM from three European tertiary referral centers (690 with LVOT obstruction and gradient ≥30 mmHg, of whom 316 underwent alcohol septal ablation and 250 underwent septal myectomy) who were followed for an average of 7.6 years, there was no significant difference in 10-year survival between patients with or without LVOT obstruction regardless of treatment (medical, alcohol septal ablation, or septal myectomy in patients with LVOT obstruction) [78]. However, sudden cardiac death was lower in patients treated with septal myectomy compared with both alcohol septal ablation and medical therapy. (See 'Sudden cardiac death' above.)
Advantages of each procedure — Although the medium-term outcomes with both septal myectomy and alcohol septal ablation are similar, there are certain advantages that are inherent to each procedure. In the absence of any prospective trial directly comparing the long-term efficacy of each procedure, the importance of proper patient selection is critical to ensuring that the procedure most likely to provide an individual patient with success is chosen [5,40,88-92].
Advantages of septal myectomy — Advantages of surgical septal myectomy, compared to alcohol septal ablation, include:
●Higher success rate for anatomic relief of LVOT obstruction (approximately 90 to 95 percent compared with 80 to 90 percent for alcohol septal ablation).
●Immediate sustained relief of LVOT obstruction and concomitant mitral regurgitation as compared with up to three-month delay in improvement following alcohol septal ablation.
●The ability to obtain tissue for histologic review, thereby allowing for diagnosis of alternative pathology. Among 2472 consecutive patients diagnosed with HCM and LVOT obstruction who underwent septal myectomy at an HCM referral center between 2002 and 2018, 331 patients (13 percent) had postoperative histologic confirmation of an alternative diagnosis (primarily hypertensive heart disease but also storage disorders [mainly Fabry disease] and cardiac amyloidosis) [93].
●Lower incidence of CHB requiring pacemaker insertion (approximately 3 percent with septal myectomy versus 10 percent for septal ablation guided by myocardial contrast echocardiography).
●Better symptom resolution has been observed with myectomy than with septal ablation in patients ≤65 years old [26].
●Proven long-term (>20 years) efficacy; similar data with septal ablation are not yet available. (See 'Long-term outcomes' above.)
●Greater likelihood of successful relief of LVOT obstruction and symptoms in patients with massive septal hypertrophy.
●No risk of coronary dissection and minimal risk of myocardial damage remote from the septum.
●The ability to treat concomitant problems, such as mid-ventricular obstruction, coronary artery muscle bridges, coronary disease requiring CABG, right ventricular outflow obstruction, and intrinsic mitral valve disease (requiring repair or replacement) [27,94]. In patients with HCM and atrial fibrillation, myectomy affords the opportunity to perform an adjunctive MAZE procedure to decrease the likelihood of future episodes of atrial fibrillation or to decrease the burden of atrial fibrillation episodes.
●Evidence suggests that myectomy may reduce the risk of SCD and appropriate ICD discharges [45,48].
Advantages of alcohol septal ablation — Advantages of alcohol septal ablation, compared to surgical myectomy, include:
●Avoidance of sternotomy, cardiopulmonary bypass and their associated risks. This is of particular importance in elderly patients, in those patients with comorbidities which significantly increase operative risk, or in patients with a substantial fear of cardiac surgery.
●Shorter hospital stay and recovery time [84].
●Lower risk of ventricular septal defect.
●The ability to treat CAD which requires percutaneous intervention.
●Less expense.
Repeat septal reduction therapy for recurrent or residual symptomatic LVOT obstruction — The vast majority of patients who undergo an invasive septal reduction therapy experience significant reduction in LVOT obstruction with improvement or resolution of their symptoms. However, occasional patients have persistent limiting symptoms, typically associated with a significant residual LVOT gradient (<2 percent of patients following surgical septal myectomy, up to 10 percent of patients following alcohol septal ablation), and may be candidates for a second invasive septal reduction therapy in an effort to further relieve obstruction and improve symptoms.
Patients with residual LVOT obstruction and limiting symptoms after an initial invasive septal reduction therapy, and who are considered candidates for a second procedure, should be considered for a second invasive procedure, although this is entirely based on expert opinion. The choice of surgical septal myectomy or alcohol septal ablation for the second procedure depends on the individual circumstances of why the first procedure failed and the wishes and desires of the patient. In one retrospective single-center cohort of 375 patients who underwent alcohol septal ablation, 20 patients (5 percent) subsequently underwent surgical septal myectomy for refraction symptomatic LVOT obstruction [95]. Following the second procedure, patients experienced a significant improvement in functional status, exercise time, and LVOT obstruction, although there was a 12 percent chance of needing a permanent pacemaker (2 of 17 patients, as 3 already had a pacemaker following alcohol septal ablation). Intuitively the risk of ventricular septal defect may be increased as well for patients who undergo both procedures, although there are no data on this.
Pacemaker therapy
Dual chamber (RA and RV) pacing — In the early 1990s, dual chamber pacing was presented as an alternative to myectomy to improve symptoms by lowering left ventricular outflow tract (LVOT) gradients. By programming forced RV pacing, the ventricular septum moves toward the right ventricle during systole, resulting in widening of the LVOT and reduction in mitral valve contact with the septum in patients with systolic anterior motion (SAM) of the mitral valve. Observational studies and small randomized trials suggested symptomatic and functional benefit from pacing [96-98]. However, subsequent data from single- and multicenter randomized trials, particularly M-PATHY, demonstrated average LVOT gradient reductions of only 50 percent without improvement in exercise capacity [35,99,100]. The perceived symptomatic improvement was largely explained as a placebo effect [100,101]. Only a small subset of predominantly older patients with localized mild septal hypertrophy may benefit from dual chamber pacemaker treatment. A 2012 systemic review by the Cochrane Collaboration found that the majority of the published studies provided inadequate data or had a high risk of bias, and additional higher quality data were needed prior to conclusively stating if pacing was beneficial or not [102].
As a result of the data derived from the numerous randomized trials, pacing is not considered a primary treatment of HCM and should only be considered in HCM patients who are not candidates for invasive septal reduction therapies (myectomy or alcohol septal ablation). We agree with the 2011 ACCF/AHA Task Force on Practice Guidelines that "patients with HCM who have had a dual-chamber device implanted for non-HCM indications" may undergo a "trial of dual-chamber atrial-ventricular pacing (from the right ventricular apex) for the relief of symptoms attributable to LVOT obstruction" [5].
While patients with HCM who are candidates for other therapies should not undergo implantation of a permanent pacemaker strictly for the treatment of symptoms of LVOT obstruction, permanent pacing may be considered in medically refractory symptomatic patients with HCM and significant resting or provoked left ventricular outflow tract obstruction who are not candidates or who do not want current invasive septal reduction therapies.
Biventricular pacing — Small studies have suggested the possibility of cardiac resynchronization therapy with biventricular pacing in patients with HCM and LVOT obstruction [103] or left bundle branch block [104]. Additional data are required prior to making any recommendations regarding the utility of biventricular pacing in patients with HCM.
CHOOSING THE APPROPRIATE NONPHARMACOLOGIC THERAPY FOR SYMPTOMATIC LVOT OBSTRUCTION — Many patients with HCM who have symptomatic left ventricular outflow tract (LVOT) obstruction in spite of medical therapy are potential candidates for either surgical septal myectomy or alcohol septal ablation. Choosing one procedure over the other requires knowledge of the anatomy of the LVOT obstruction, concomitant cardiac problems (eg, coronary artery disease, mitral valve disease), and medical comorbidities along with the patient's preferences. In addition, the presence or absence of local expertise in one or both procedures may be a guiding factor in choosing which course of treatment or in referring the patient to another center for a particular treatment.
For patients with HCM who have advanced and limiting heart failure symptoms that are refractory to medical therapy, along with an LVOT gradient ≥50 mmHg at rest or following provocation (exercise echocardiography preferably), we recommend septal reduction therapy. For patients who are candidates for either surgical septal myectomy or alcohol septal ablation, we suggest surgical septal myectomy, based on greater than 50 years of experience with the procedure, clear clinical efficacy, and the ability to treat concomitant cardiac problems simultaneously. For patients in whom surgery is felt to be too high-risk due to significant comorbidities, or for patients who prefer to avoid surgery, alcohol septal ablation can be performed. This is in agreement with the 2011 ACCF/AHA 2011 Guidelines as well as the 2014 European Society of Cardiology Guidelines [5,105]. Regardless of which invasive septal reduction therapy is chosen, the procedure should be performed in a high-volume center, as the rates of in-hospital death, need for permanent pacemaker, and complications are all significantly better at high-volume centers compared with low-volume centers [87,106-108].
Additional factors to consider in choosing between surgical septal myectomy and alcohol septal ablation include the following:
●Given the potential concern that the induction of a transmural myocardial scar by the alcohol septal ablation procedure could increase future risk of ventricular arrhythmias, age is an important variable in deciding between procedures. Specifically, alcohol septal ablation should not be performed in patients <21 years old and should be discouraged in those less than 40 years of age unless there are significant contraindications to surgery.
●In addition, the anatomy of the LVOT can be slightly different in each individual patient, as a number of relevant morphologic factors can contribute substantially (or can be the predominant reason) to the generation of outflow obstruction in an individual patient (including elongated mitral valve leaflet(s), anomalous insertion of the anterolateral papillary muscle directly into the mitral valve, massive LV hypertrophy, and apically displaced papillary muscles). Since these features cannot be addressed with a percutaneous approach with alcohol septal ablation, identifying one or more of these features can sway decision-making toward surgical myectomy.
●The presence of concomitant cardiac problems (eg, coronary artery disease, mitral valve disease, and atrial fibrillation) may warrant a surgical approach since an adjunctive procedure will be required in addition to the surgical septal myectomy (ie, coronary artery bypass grafting, mitral valve replacement, or MAZE procedure).
●The presence or absence of local expertise in one or both procedures may be a guiding factor in choosing which course of treatment or in referring the patient to another center for a particular treatment.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiomyopathy".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Hypertrophic cardiomyopathy in adults (The Basics)")
●Beyond the Basics topic (see "Patient education: Hypertrophic cardiomyopathy (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Left ventricular outflow tract (LVOT) obstruction in hypertrophic cardiomyopathy (HCM) is due to systolic anterior motion (SAM) of the mitral valve (usually the anterior leaflet) caused by high LVOT blood velocities that pull the mitral valve leaflet toward the ventricular septum. This results in the anterior mitral valve leaflet contacting the septum (ie, SAM-septal contact) and mechanical impedance to blood flow during systole, which produces a pressure gradient between the LV and the aorta. (See 'Mechanism of LV outflow tract obstruction' above.)
●LVOT obstruction (≥50 mmHg) is a strong and independent determinant of progressive heart failure (HF) symptoms, HF, and stroke death in patients with HCM. (See 'Treatment options for LVOT obstruction' above.)
●The initial treatment for LVOT obstruction in most patients is a combination of one or more pharmacologic agents. (See 'Pharmacologic therapy for LVOT obstruction' above and "Hypertrophic cardiomyopathy: Medical therapy for heart failure".)
●The primary indication for invasive septal reduction therapy in patients with HCM and symptomatic LVOT obstruction is the presence of advanced HF symptoms that are refractory to maximal medical therapy with a resting or provocable gradient of ≥50 mmHg.
•Surgical septal myectomy relieves LVOT obstruction by direct removal of septal muscle. In addition, abnormalities of the mitral valve and its papillary muscles which can also contribute to the mechanism of outflow obstruction, can also be addressed at the time of septal myectomy providing optimal relief of LVOT gradient. (See 'Surgical septal myectomy' above.)
•Alcohol septal ablation relieves LVOT obstruction by creating a localized myocardial infarction of septal muscle. Following remodeling of this area, the LVOT is widened, thereby relieving LVOT obstruction. (See 'Alcohol (ethanol) septal ablation' above.)
•Both surgical septal myectomy and alcohol septal ablation can be performed in patients with lesser degrees of septal thickness (<16 mm), but in general surgery can address abnormalities of the mitral valve and its papillary muscles which can also contribute to the mechanism of outflow obstruction, providing optimal relief of LVOT gradient.
●Septal myectomy and alcohol septal ablation should be performed in centers with extensive HCM treatment experience and demonstrable low procedural mortality rates since patient selection, procedural expertise, periprocedural echocardiography, and management are important components of a successful outcome. (See 'Comparison of septal myectomy and alcohol septal ablation' above.)
●Both surgical myectomy and alcohol septal ablation can substantially lower LVOT gradients and improve limiting HF symptoms. Patients with HCM, LVOT gradient of ≥50 mmHg at rest or with provocation, and advanced and limiting HF symptoms that are refractory to medical therapy should undergo septal reduction therapy. (See 'Choosing the appropriate nonpharmacologic therapy for symptomatic LVOT obstruction' above.)
•For patients who are candidates for both surgical septal myectomy and alcohol septal ablation, we suggest surgical septal myectomy, based on extensive clinical experience with the procedure, clear clinical efficacy, and the ability to treat concomitant cardiac problems simultaneously (Grade 2C).
•For patients in whom surgery is felt to be too high-risk due to significant comorbidities, or for patients who prefer to avoid surgery, alcohol septal ablation can be performed.
