Percutaneous Transluminal Septal Myocardial Ablation (PTSMA)

Number: 0558

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses percutaneous transluminal septal myocardial ablation (PTSMA).

1. Medical Necessity

   Aetna considers percutaneous transluminal septal myocardial ablation (PTSMA) by alcohol-induced septal branch occlusion medically necessary for hypertrophic obstructive cardiomyopathy (HOCM) in adults (21 years of age and older) when all of the following criteria are met:

   1. Member has severe symptoms (e.g., dyspnea, angina pectoris, [pre]syncope, palpitations or heart failure) for at least 6 months despite optimal drug therapy (e.g., beta-blockers, calcium-antagonists), dual chamber pacing therapy and/or ineffective previous surgical myotomy/myectomy; and
   2. Member is classified as New York Heart Association class III or IV (see below); and
   3. Member has a classical, asymmetric subaortic HOCM identified by echocardiography, and not a mid-ventricular, a concealed membranous subaortic stenosis, nor supravalvular form; and
   4. Echocardiography shows left ventricular wall thickness of greater than 13 mm in adults in the absence of another cause for left ventricular hypertrophy; 15 mm in an athlete; and
   5. Member has systolic anterior motion of the mitral valve on echocardiography; and
   6. Member has a resting left ventricular outflow tract (LVOT) gradient of greater than 30 mm Hg or a stressed gradient of greater than 60 mm Hg, or member has less severe symptoms and LVOT of greater than 50 mm Hg at rest or greater than 100 mm Hg under stress; and
   7. Member does not have coronary artery disease that would preclude performance of the procedure.

   Aetna considers PTSMA medically necessary for young (age of 5 to 20 years) individuals with HOCM who have failed medical therapies (e.g., amiodarone, beta-blockers, and verapamil) or have contraindications to surgery; and meet the afore-mentioned selection criteria for adults.

2. Experimental, Investigational, or Unproven

   Aetna considers percutaneous transluminal septal myocardial ablation experimental, investigational, or unproven for all other indications (including HOCM complicated by myocardial bridge) because of insufficient evidence of its safety and effectiveness.

   Aetna considers ultrasound-guided percutaneous transluminal septal myocardial ablation experimental, investigational, or unproven for the treatment of hypertrophic obstructive cardiomyopathy because of insufficient evidence of its safety and effectiveness.
   
   Aetna considers the SESAME (Septal Scoring Along Midline Endocardium) procedure experimental, investigational, or unproven for the treatment of hypertrophic cardiomyopathy because of insufficient evidence of its safety and effectiveness.

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
CPT codes covered if selection criteria are met:
Percutaneous transluminal septal myocardial ablation – no specific code
93583	Percutaneous transcatheter septal reduction therapy (eg, alcohol septal ablation) including temporary pacemaker insertion when performed
CPT codes not covered for indications listed in the CPB:
Ultrasound-guided percutaneous transluminal septal myocardial ablation, SESAME (Septal Scoring Along Midline Endocardium) -no specific code
Other HCPCS codes related to the CPB:
C1886	Catheter, extravascular tissue ablation, any modality (insertable)
ICD-10 codes covered if selection criteria are met:
I42.1	Obstructive hypertrophic cardiomyopathy
ICD-10 codes not covered if selection criteria are met:
I42.2	Other hypertrophic cardiomyopathy

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Background

Hypertrophic obstructive cardiomyopathy (HOCM), also known as idiopathic hypertrophic subaortic stenosis, is a primary, sometimes familial and genetically determined myocardial hypertrophy with an incidence of about 0.2%. About 25% of the patients have dynamic left ventricular outflow tract (LVOT) obstruction, which usually develops during puberty and increases in severity until the age of 18 to 20 years. Not infrequently, HOCM is diagnosed for the first time in the elderly.

Echocardiography is the primary method for diagnosing HOCM. This condition is characterized by a super-normally contracting left ventricle, asymmetric septal hypertrophy, which affects mainly the interventricular septum, increased ventricular wall thickness (left ventricular wall thickness of greater than 13 mm in adults in the absence of another cause for left ventricular hypertrophy; 15 mm in an athlete), and systolic anterior motion of the mitral valve. Although patients with hypertrophic cardiomyopathy usually have super-normal ejection fractions, they have thickened and poorly compliant left ventricles in which left ventricular filling pressure is markedly elevated and probably is responsible for most of the symptoms.

Cardiac hypertrophy is associated with LVOT obstruction in only a minority of HOCM patients. The LVOT gradient is generated by systolic anterior motion of a mitral valve leaflet and its coaptation with the interventricular septum. Left ventricular outflow tract obstruction does not generally increase during exercise because of adequate venous return, but it often worsens or becomes apparent in the immediate post-exercise period. Maneuvers that decrease preload or afterload or increase myocardial contractility, such as stress, dehydration, and sudden adoption of an erect posture often induce symptoms. The significance of the LVOT gradient has been debated, but it is now generally accepted that it is an important determinant of the clinical course.

Asymptomatic adult patients probably do not require therapy or risk stratification studies, unless there is a malignant family history of sudden death or occupational need (airline pilot). Management decisions are dominated by the need to address sometimes disabling symptoms of dyspnea, angina pectoris, stress-induced syncope, palpitations or heart failure, and risk of sudden death. Treatment of symptomatic patients with HOCM aims at reduction of the LVOT gradient and improvement of diastolic filling either by pharmacological therapy with negative inotropic drugs (beta-blockers, calcium-antagonists), permanent DDD pacemaker therapy (i.e., dual- chamber, dual-pacing, dual-sensing), or surgical myotomy/myectomy.

At least 10% of patients with severe HCOM are unresponsive to medical therapy or report severe side effects of optimum doses of drugs. Successful DDD pacing at the apex of the right ventricle induces a paradoxic motion of the inter-ventricular septum away from the mitral valve, reducing LVOT obstruction. Long-term studies have uniformly confirmed that DDD pacing can reduce LVOT gradient and improve severe drug-refractory symptoms in most patients with HOCM, obviating the need for cardiac surgery. A large European study has demonstrated that when follow-up was sufficiently long to allow adaptive changes and to eliminate carryover effects, DDD pacing conferred substantial symptomatic and hemodynamic benefits. As some of the beneficial effects of DDD pacing become apparent after prolonged pacing, it is important to allow sufficient time for chronic DDD pacemaker therapy.

Left ventricular myotomy and myectomy (Morrow's procedure) has been the standard therapy for patients with severe symptoms (New York Heart Association (NYHA) functional class III to IV) that persist despite adequate pharmacotherapy and DDD pacing. Using an aortic root approach, this involves surgically removing enough muscle from the septum to sufficiently widen the outflow tract. The procedure improves or eliminates symptoms and LVOT gradient in 90% of patients. The success of the procedure and the operative mortality are very much dependent on the skill and experience of the surgeon but may be as low as 1 to 2%. Complications include heart block, ventricular septal defect, 1 to 2% annual mortality during follow-up, late aortic valve incompetence, and LV dysfunction. Sometimes, a prosthetic mitral valve replacement must be done to eliminate systolic anterior motion and LVOT obstruction, but the patient requires life-long anti-coagulation and is subject to the risk of prosthetic malfunction.

In 1994, as an alternative to surgery, non-surgical percutaneous transluminal septal myocardial ablation (PTSMA) by alcohol-induced septal branch occlusion was introduced to decrease LVOT gradient and improve symptoms in patients with HOCM. This method was substantially improved by the introduction of echocardiographic guidance in 1996. With this guidance, the reduction in the LVOT gradient is optimized and ablation of inappropriate areas can be avoided. Consequently, the hemodynamic results and symptoms are improved, and the incidence of complications is reduced. The most common procedural complication is the development of high-grade trifascicular block necessitating implantation of a permanent pacemaker in 25% of patients. Other complications include death, ventricular arrhythmias, and coronary artery dissection.

Percutaneous transluminal septal myocardial ablation involves transcatheter selection of 1 or 2 small septal branches of the left anterior descending artery, threading a small, short, low-pressure angioplasty balloon into position to occlude the artery, and the instillation of absolute alcohol into the myocardium. The resultant localized myocardial infarction reduces the amount of septal myocardium, opening up the LVOT. Compared with surgical myectomy, the literature shows that PTSMA has the advantage of being minimally invasive, easily repeated, and with relatively low major morbidity/mortality risk for patients with co-morbid conditions.

In one study, 70% of patients during short-term follow-up showed impressive clinical improvement as well as diminution of intra-ventricular pressure gradient and a marked increase in maximal workload during exercise testing. During a 12-month follow-up period, there was a significant decrease of functional class, a reduced rate of syncope, and a reduced degree of mitral insufficiency. Exercise capacity, oxygen uptake and the cardiac index increased, intra-ventricular gradient, the end diastolic pressure of the left ventricle and the left atrial size decreased. Additionally, there was a decrease in the septal thickness with increase in the cross-sectional area of the outflow tract. PET examination showed an ablation-induced local myocardial defect. There was also evidence for improved diastolic function. Electrophysiological and Holter monitor studies indicated no increased arrhythmogenicity. The in-hospital mortality rate amounts to about 1.8% and in 15% of patients a second PTSMA is necessary.

There appears to be little doubt in the literature that favorable morphologic and functional results can be achieved by PTSMA, and that short-term follow-up studies show clinical and objective improvement, as well as further gradient reduction due to left ventricular remodeling. Currently, randomized, prospective studies of larger patient series are being conducted to compare the short- and long-term effects of PTSMA with the major treatment options (e.g., pharmacologic therapy, myotomy/myectomy, mitral valve replacement, pacemaker implantation). The outcomes of these studies will be needed to determine PTSMA’s ultimate role in the treatment of HOCM, as well as provide guidance concerning the optimal treatment of patients with HOCM.

The American Heart Association and the American College of Cardiology have no position statements on this procedure.

An assessment by the National Institute of Clinical Excellence (NICE, 2003) concluded that current evidence on the safety and efficacy of non-surgical reduction of the myocardial septum appears adequate to support the use of the procedure, provided that normal arrangements are in place for consent, audit and clinical governance.

Percutaneous transluminal septal myocardial ablation is best performed in centers with experience with this procedure. Patients treated with PTSMA should be entered into a registry of these procedures.

Zhang and colleagues (2011) retrospectively summarized the effect of non-medical therapies for pediatric patients with HOCM. From November 2008 to June 2010, 4 children with drug-refractory HOCM were admitted to the authors' hospital. Their ages were 14, 7, 9 and 6 years old, respectively. Their body weights were 38, 17, 21.5 and 17 kg, respectively. Before operation, the LVOT gradients were 60, 147, 58 and 114 mm Hg (1 mm Hg = 0.133 kPa), respectively; mitral regurgitation (MR) areas were 2.2, 7.3 cm(2) and 2.9 cm(2), respectively, except that it was trivial in 1 case. Percutaneous transluminal septal myocardial ablation was performed in case 1 and 2. Septal myectomy (SM) was performed in case 3 and 4. Follow-up was first performed right after operation or before discharge, then 1 month, 3 months, 6 months, and 12 months after operation, and then once-yearly. The follow-up period was 1 to 18 (9.3 +/- 8.1) months. All patients experienced relieved symptoms; 3 of them had their NYHA functional class improved except case 2. Echocardiography revealed that LVOT gradients right after operations were 38, 79, 20 and 0 mm Hg, respectively, suggesting significant improvement of LVOT obstruction in all patients. During follow-up, case 2 suffered from recurrence of LVOT obstruction, while the other 3 cases showed sustained relief. In the last follow-up, the LVOT gradients of the 4 patients were 19, 168, 16 and 0 mm Hg, respectively. Echocardiography also revealed that MRs of all patients were significantly reduced, even in case 2 whose LVOT gradient rebounded, with no recurrence during follow-up. Severe complications were absent, such as ventricular septum perforation, cardiac tamponade, ventricular tachycardia or ventricular fibrillation. No one suffered from complete heart block. Transient complete right bundle branch block (CRBBB) was observed in case 1 after PTSMA and converted to intra-ventricular block after 1 month. Complete left bundle branch block (CLBBB) was present in both case 3 and 4, who received SM. In case 4, it converted to intra-ventricular block after 1 month while in case 3 CLBBB persisted. The authors concluded that the initial experience showed that PTSMA and SM were safe and effective for drug-refractory symptomatic HOCM children, with satisfactory short-term results. They stated that further studies are needed to evaluate the long-term results and complications.

Akita and colleagues (2018) stated that plasma brain natriuretic peptide (BNP) levels are associated with clinical outcomes in patients with HOCM. However, the prognostic value of plasma BNP level changes before and after PTSMA remains unclear. These researchers examined if repeated BNP measurements following PTSMA provide prognostic information regarding the response to PTSMA in patients with drug-refractory HOCM. They measured the plasma BNP levels serially before and after PTSMA, and evaluated the relationship between the changes in plasma BNP levels and clinical improvement in 47 patients. The patients were assigned to 2 groups based on the reduction in the NYHA class greater than or equal to 1 (good responder) or less than 1 (poor responder) before and after PTSMA. The Kansas City Cardiomyopathy Questionnaire (KCCQ) was used to measure health status. The plasma BNP levels gradually decreased after PTSMA, although the levels plateaued 3 months until 12 months after PTSMA. Although the plasma BNP levels and resting LVOT peak pressure gradient before PTSMA were comparable between the groups, the ratio of the BNP levels before and after PTSMA in the good responder group was significantly lower than that in the poor responder group (0.43; range of 0.24 to 0.68) versus 0.78 (range of 0.62 to 0.93), p = 0.002). The KCCQ score changes in the good responder group were significantly higher than those in the poor responder group. The authors concluded that the plasma BNP level ratio was associated with long-term clinical improvement of heart failure (HF) following PTSMA for drug-refractory HOCM.

Percutaneous Transluminal Septal Myocardial Ablation for the Treatment of Severe but Asymptomatic Hypertrophic Obstructive Cardiomyopathy

Arslan and colleagues (2021) noted that symptoms justify invasive treatment in HOCM patients with LVOT obstruction. Adverse structural and functional changes (re-modeling) in the heart occur preceding heart failure and sudden cardiac death. Early invasive treatment in asymptomatic patients may reverse adverse re-modeling to the same extent as in symptomatic patients. These researchers examined the impact of PTSMA on re-modeling in asymptomatic patients with HOCM and severe LVOT obstruction. Reverse re-modeling after PTSMA in severe but asymptomatic LVOT obstruction (RASTA) study is a prospective, randomized, single-blind trial (ClinicalTrials.gov number: NCT04230551). A total of 10 asymptomatic HOCM patients with an exertional LVOT gradient greater than or equal to 50 mmHg (or greater than 30 mmHg in rest) are randomized 1:1 to PTSMA versus conservative therapy, in the absence of mitral valve disease or other indications for cardiac surgery; 5 symptomatic (reference group) will undergo PTSMA according to the current guidelines. Re-modeling is evaluated using extensive cardiac imaging with trans-thoracic echocardiography (TTE) and late gadolinium enhancement cardiac magnetic resonance (CMR) at baseline and during follow-up at 1, 12, and 24 months. Extracellular volume fraction, global, and regional strain analysis, geometry, pressure gradients and changes in four-dimensional (4D) velocity mapping are primary parameters to study (reversal of) adverse re-modeling. The authors concluded that the RASTA study gives insight in cardiac re-modeling that may occur in asymptomatic patients after PTSMA. It will provide arguments whether to pursue (or not) a larger trial with clinical endpoints in asymptomatic HOCM patients with severe LVOT obstruction.

Young Patients with Medically Refractory Hypertrophic Obstructive Cardiomyopathy

Veselka et al (2014) stated that the long-term safety and effectiveness of alcohol septal ablation (ASA) has recently been demonstrated; however, there is still debate regarding the outcome of younger patients who should be treated using myectomy, according to American College of Cardiology Foundation/American Heart Association (ACAF/AHA) guidelines. In a retrospective study, these investigators examined the long-term outcome of patients 50 years of age or younger (42 ± 7 years) after ASA for the treatment of HOCM. They evaluated consecutive, highly symptomatic patients aged 50 years of age or less with HOCM who underwent ASA. Institutional databases of 3 cardiovascular centers identified 290 patients with HOCM who underwent ASA; 75 (26%) of them were aged 50 years or younger at the time of their 1st ASA. Median duration of follow-up was 5.1 years (range of 0.1 to 15.4 years). Four patients (5%) died during the study period (438 patient-years; the annual mortality rate was 0.91%; 95% CI:, 0.25% to 2.34%; the annual mortality rate combined with the 1st appropriate implantable cardioverter-defibrillator discharge was 1.43%; 95% CI: 0.52% to 3.10%). Survival free of all-cause mortality at 1, 5, and 10 years was 97% (95% CI: 89% to 99%), 94% (95% CI: 84% to 98%), and 94% (95% CI: 84% to 98%), respectively. The authors concluded that results of this study focused on HOCM patients aged 50 years or younger who underwent ASA suggested a low risk of all-cause death or appropriate implantable cardioverter-defibrillator discharge in the long-term follow-up.

Liebregts et al (2017) noted that the ACCF/AHA guidelines reserve ASA for older patients and patients with serious co-morbidities. Data on long-term age-specific outcomes following ASA were scarce. These investigators examined the safety and outcomes of ASA in younger patients with HOCM. A total of 1,197 patients (mean age of 58 ± 14 years) underwent ASA for HOCM. Patients were divided into young (mean age of 42 ± 8 years), middle-age (mean age of 58 ± 4 years), and older (mean age of 73 ± 5 years) groups. In particular, the young group comprised of “very young” (13 to 35 years of age), and “young” (36 to 50 years of age). The 30-day mortality and pace-maker implantation rates were lower in young compared with older patients (0.3% versus 2% [p = 0.03], and 8% versus 16% [p < 0.001], respectively); 95% of young patients were in NYHA functional class I or II at last follow-up. During a mean follow-up period of 5.4 ± 4.2 years, 165 patients (14%) died. Annual mortality rates of young, middle-age, and older patients were 1%, 2%, and 5%, respectively (p < 0.01). Annual adverse arrhythmic event rates were similar in the 3 age groups at about 1% (p = 0.90). Independent predictors of mortality in young patients were age, female sex, and residual LVOT gradient. Furthermore, young patients treated with 2.5 ml or greater alcohol had a higher all-cause mortality rate (0.6% versus 1.4% per year in patients treated with less than 2.5 ml, p = 0.03). The authors concluded that ASA in younger patients with HOCM was safe and effective for relief of symptoms at long-term follow-up. These investigators proposed that the indication for ASA could be broadened to younger patients.

Batzner et al (2022) stated that since its introduction, PTSMA was discussed as therapeutic option only in elderly symptomatic patients with HOCM. These investigators reported on long-term follow-up following PTSMA with respect to patient's age. Between May 2000 and June 2017, the authors treated 952 consecutive HOCM patients with PTSMA; 133 (14.0%) patients were less than 40 years of age (Group A; mean age of 30.3 ± 7.6; 26.3% female), 422 (44.3%) patients were between 40 years of age or younger and less than 60 years of age (Group B; mean age of 50.6 ± 5.8; 27.0% female), and 397 (41.7%) patients were 60 years of age or older (Group C; 69.7 ± 6.1; 60.2% female). In particular, Group A comprised 20 patients of less than 20 years of age, 31 patients of 21 to less than 30 years of age, and 82 patients of 30 to less than 40 years of age. After PTSMA, the need of pace-maker implantation was lowest in Group A (3.8%, p < 0.01 each) compared with Group B (9.2%) and Group C (14.1%) during hospital stay. One patient in Groups A and C died during hospital stay, each. Follow-up was longer in Group A (7.4 ± 5.5 years) compared with Group C (5.6 ± 4.8 years; p < 0.001) and comparable with Group B (6.5 ± 5.1 years). Mortality was highest in Group C (13.1%; p < 0.0001 each) compared with Group A (1.5%) and Group B (4.3%). In Group A, no patient died from cardiac reason, whereas 5 patients died from cardiac reasons in Group B, and 7 patients in Group C. Sudden cardiac death (SCD) was not observed in Group A, whereas 3 patients in Group B, and 1 patient in Group C suffered SCD. The authors concluded that mortality following PTSMA was predominantly due to non-cardiac reasons and mainly observed in elderly patients. Survival in young patients was not affected by cardiac mortality. These investigators stated that in experienced centers with careful patient selection, PTSMA was safe in young patients.

Lawin et al (2022) noted that data regarding ASA in young patients with HOCM were scarce. These investigators examined the safety and effectiveness of ASA in patients 25 years of age or younger. All ASAs between 2002 and 2020 at the authors’ institution were assigned to a group of patients 14 to 25 years of age (group 1) and a reference group of greater than 25 years (group 2). A total of 1,264 procedures were analyzed in group 2 (58.6 ± 13.5 years) and 41 procedures in group 1 (20.9 ± 3.3 years). The baseline inter-ventricular septal diameter (IVSD) was higher in group 1 (26.0 ± 6.5 mm versus 21.3 ± 4.4 mm; p < 0.0001). There was no difference in baseline left ventricular outflow tract gradient (LVOTG) (group 1: 54.4 ± 24.4 mmHg; group 2: 52.4 ± 36.6 mmHg; p = n.s.). A previous cardiac device was more often observed in group 1 (31.7% versus 9.0%; p < 0.0001). Symptoms were improved after 6 months (group 1: mean NYHA class 2.5 at baseline and 1.3 at follow-up; p < 0.0001; group 2: mean NYHA class 2.7 at baseline and 1.4 at follow-up; p <0 .0001). IVSD (group 1: 20.3 ± 8.2 mm; group 2: 16.8 ± 5.7 mm; p < 0.0001 for each group compared to baseline), and LVOTG improved during follow-up (group 1: 25.5 ± 20.0 mmHg; group 2: 22.1 ± 21.7 mmHg; p < 0.0001 for each group). Intra-hospital mortality was 0.0% in patients 14 to 25 years, and 0.9% in the reference group. Persistent AV-block was observed in 12.2% of the group 1 and 15.9% of the group 2 patients (p = n.s.). The authors concluded that ASA was safe and effective in HOCM patients 14 to 25 years of age in experienced centers.

Achim et al (2023) stated that percutaneous and surgical therapies for septal reduction for hypertrophic cardiomyopathy have been going head-to-head for the past 2 decades with similar outcomes and mortality rates, although contemporary myectomy appeared to materialize its superiority. However, on closer analysis, the external validity of studies advocating myectomy does not translate to all centers. These investigators examined the most recent data on septal reduction therapy and phenotyped the appropriate patient for each of the 2 approaches. The key to similar low mortality rates between ventricular septal myectomy and ASA appeared to be proper patient selection performed in high volume clinical environments. The authors concluded that a RCT comparing both septal reduction methods remains elusive due to practical concerns; however, there is a strong signal that the outcome of ASA is heavily dependent on appropriate patient selection, longitudinal and multi-disciplinary care, as well as operator expertise. The procedure should only be performed in specialized centers and to older adults, due to lack of long‐term data. The remaining majority of patients should be referred to a center with surgical expertise, which adds mitral valve repair to myectomy at the time of index operation, and online imaging to ensure a tailored myectomy. However, age should not be the only factor favoring one procedure over the other as ASA remains a safe, effective and feasible option for younger patients. The excellence of the center and the patient's choice ultimately dictates the therapeutic course.

Sivakumar and Jain (2024) noted that surgical myectomy is recommended for symptomatic HOCM following optimal pharmacotherapy; PTSMA is reserved for high-risk adults. Symptomatic patients below 25 years underwent either surgery or PTSMA after heart-team discussion and informed consent. Echocardiography assessed gradients in surgical group. PTSMA group underwent invasive trans-septal hemodynamic assessment, selective coronary angiography and super-selective cannulation of septal perforators using microcatheters. Contrast echocardiography via the micro-catheter identified the myocardial target for PTSMA. Hemodynamic and electrocardiographic monitoring guided alcohol injection. Both groups were continued on beta-blockers. Symptoms, echocardiographic gradients and brain natriuretic peptide (NTproBNP) measurements were assessed on follow-up. In this study, a total of 12 patients aged 5 to 23 years (body weight of 11 to 98 kg) formed the study group. Indications for PTSMA in 8 patients included abnormal mitral valve anatomy warranting replacement (n = 3), Jehovah's witness (n = 2), severe neurodevelopmental and growth retardation (n = 1) and refusal of surgery (n = 2). PTSMA targeted 1st perforator (n = 5), 2nd perforator (n = 2) and anomalous septal artery from left main trunk (n = 1). Outflow gradient reduced from 92.5 ± 19.7 to 33.1 ± 13.5 mmHg. At a median follow-up of 38 months (range of 3 to 120 weeks), the peak instantaneous echocardiographic gradient was 32 ± 16.5 mmHg. Gradient reduced in 4 surgical patients from 86.5 ± 16.3 mmHg to 42 ± 14.7 mm Hg. All patients were in NYHA class I/II on follow-up. The mean NTproBNP in PTSMA group reduced from 6,084 ± 3,628 pg/ml to 3,081 ± 2,019 pg/ml; it was 1,396 and 1,795 pg/ml in surgery. The authors concluded that PTSMA may be considered in medically refractory high-risk young patients. It relieved symptoms and reduced gradient. These investigators stated that although surgery is preferred in young patients, PTSMA may have a role in selected patients.

Hypertrophic Obstructive Cardiomyopathy Complicated by Myocardial Bridge

Wu et al (2023) noted that PTSMA is an effective means for symptomatic patients with hypertrophic cardiomyopathy (HCM). These investigators presented a rare case in which myocardial bridge (MB) was exacerbated in a patient with HCM treated with PTSMA. They described a case of HCM with palpitations and exertional dyspnea for 2 years. There was no obvious epicardial coronary artery compression before PTSMA. Typical angina occurred 2 months after PTSMA. Coronary angiography (CAG) showed no obvious stenosis of the coronary arteries, but an exacerbated MB in the middle part of the left anterior descending artery. The authors stated that this patient with HCM presented with typical angina, which might be caused by the rare exacerbation of the MB after PTSMA; therefore, patients with MB should carefully choose PTSMA. These investigators stated that further research is needed among a larger population to examine the impact of PTSMA on MB. An evaluation method of the risk and benefit of PTSMA is needed for HCM patients complicated with MB. Some characteristics from pre-operative echocardiogram (Echo), coronary computed tomography angiography (CTA), CAG, and cardiac magnetic resonance imaging (CMR) may be helpful in determining treatment strategies.

Modified Morrow Septal Myectomy Procedure for Bi-Ventricular Hypertrophic Cardiomyopathy

Tan et al (2024) stated that right ventricular involvement in hypertrophic cardiomyopathy is uncommon. In a retrospective study, these researchers examined clinical outcomes of the modified septal myectomy in patients diagnosed with bi-ventricular hypertrophic cardiomyopathy (BHCM), a subject seldom explored in the literature. This trial was carried out from January 2019 to January 2023, enrolling 12 patients with BHCM. Each patient underwent a modified septal myectomy and was followed post-operatively. Clinical data and echocardiographic parameters, including the ventricular outflow tract peak pressure gradient and maximum inter-ventricular septum thickness, were collected and analyzed. The study cohort had a median age of 43.0 (inter-quartile range [IQR] 14.5 to 63.0) years at surgery, with 4 patients (33.3%) being children; 2 patients (16.7%) previously underwent PTSMA. Surgical relief of bi-ventricular outflow tract obstruction (BVOTO) was achieved in 5 patients (41.7%), aside from those managed solely for left ventricular outflow tract obstruction. In 5 instances, three-dimensional (3D) printing technology assisted in surgical planning. The post-operative inter-ventricular septum thickness was significantly reduced (21.0 mm pre-operative versus 14.5 mm post-operative, p < 0.001), effectively eliminating residual ventricular outflow tract obstruction. There were no severe complications, such as septal perforation or 3rd-degree atrio-ventricular block. During a mean follow up of 21.2 ± 15.3 months, no sudden deaths, residual outflow tract obstruction, permanent pace-maker implantation, recurrent systolic anterior motion, or re-operations were reported. The authors concluded that the findings of this trial confirmed that the modified septal myectomy remains the gold standard treatment for BHCM, improving patient symptoms and quality of life (QOL). BVOTO relief could be safely and effectively attained through septal myectomy via trans-aortic and pulmonary valve approaches in selected patients. For intricate cases, the use of 3D printing technology as a pre-operative planning tool is advised to optimize surgical precision and safety.

Ultrasound-Guided Percutaneous Septal Precision Chemical Ablation for Hypertrophic Obstructive Cardiomyopathy

In a single-center study, Cao et al (2025) examined the safety and effectiveness of ultrasound (US)-guided percutaneous septal precision chemical ablation in the treatment of HOCM. From December 2020 to July 2024, a total of 27 patients with HOCM without large target septal branches (diffuse multiple branches, all less than 1 mm in diameter) were enrolled and underwent US-guided percutaneous septal chemical ablation. Intra-operative LVOTG, post-operative cardiac troponin I (cTnI), complications, as well as changes in the 36-Item Short Form Survey (SF-36) score, NYHA functional classification and echocardiography parameters in 1 year post-PTSMA were monitored and analyzed. Immediate post-operative LVOTG values monitored by catheter and echocardiography were both significantly decreased (both p < 0.05) in the 27 patients, whereas the cTnI level was increased after PTSMA treatment (p < 0.05). One patient developed transient complete right bundle branch block during the procedure. At the 1-year follow-up, these patients demonstrated significantly increased scores in all the 8 domains of the SF-36 scale, and markedly improvement in echocardiography-based LVOTG value (p < 0.05) and NYHA functional classification (p < 0.05). However, no significant change were observed in the mean inter-ventricular septal thickness (IVSTh) and left ventricular ejection fraction (LVEF) before and after operation (p > 0.05). The authors concluded that US-guided precision PTSMA with gelatin sponge was a safe and effective therapeutic approach for HOCM patients, which can reduce the left ventricular outflow tract obstruction and greatly improved the QOL of these patients. Moreover, these researchers stated that since this was a single‐center study with a small sample size (n = 27) and a follow‐up period of only 1 year, further investigations are needed to examine the long‐term safety and effectiveness of this approach.

SESAME (Septal Scoring Along Midline Endocardium) Procedure

Greenbaum et al (2022) noted that transcatheter mitral valve replacement (TMVR) risks left ventricular outflow tract (LVOT) obstruction from permanent displacement of the anterior leaflet and/or the implant itself in cases of hypertrophied ventricles.  While LAMPOON mitigates the risk associated with displacement of the anterior mitral leaflet, obstruction from the TMVR is often addressed with ventricular septal reduction.  Ablation with either alcohol or radiofrequency (RF) risks geographic miss, inadequate debulking, as well as complete heart block.  It also requires time-dependent myocardial necrosis, which delays therapeutic TMVR.  The researchers developed a novel transcatheter electrosurgical myotomy mimicking classic surgical myectomy to overcome these limitations.  They reported the 1st SESAME (Septal Scoring Along Midline Endocardium) procedure to treat hypertrophic cardiomyopathy and allow TMVR.  This case entailed an 80-year-old woman who had concomitant symptomatic obstructive hypertrophic cardiomyopathy (resting/provoked LVOT gradients 54/83 mmHg), bioprosthetic aortic regurgitation s/p SAPIEN3 TAVR, mitral annular calcification (MAC)-related mitral stenosis, as well as RV permanent pacemaker-dependence.  Surgery was considered prohibitively high-risk.  She remained symptomatic despite successful transcatheter aortic valve replacement (TAVR).  Her mean trans-mitral gradient was 1 5mmHg.  Her mitral annulus appeared suitable for off-label Sapien3 implantation; however, the predicted skirt-neo-LVOT and neo-LVOT created by TMVR were prohibitive (97 and 0 mm2, respectively).  Trans-coronary alcohol septal ablation was unsuccessful because of failed septal perforator coronary artery access; thus, these investigators offered compassionate SESAME.  The authors stated that this was the 1st human report of transcatheter septal myotomy.  In this case, SESAME enlarged the LVOT, relieved the LVOT gradient created by the hypertrophied septum, and created enough space for transcatheter mitral valve replacement.  Similar to surgical myotomy/myectomy, there was no further septal thinning over time.  While none occurred in this case, potential complications include iatrogenic ventricular septal defect, myocardial perforation, mitral chordal injury, conduction block requiring permanent pacemaker implantation, as well as aortic leaflet injury.  These researchers stated that SESAME, and the closely-related MIRTH (Myocardial Intramural Remodeling by endovenous teTHer) procedure, represent a family of new intra-myocardial procedures to debulk or re-shape the beating heart without cardiac surgery.  They noted that SESAME may offer a septal debulking solution for patients who are (i) at risk for LVOTO obstruction from TMVR; (ii) suffering LVOT obstruction from hypertrophic cardiomyopathy; and/or (iii) poor candidates for alcohol septal ablation.  The authors concluded that with further refinement and experience, SESAME may have advantages over alternatives.

Greenbaum et al (2024) stated that LVOT obstruction is a source of morbidity in hypertrophic cardiomyopathy (HCM) and a life-threatening complication of TMVR and transcatheter aortic valve replacement (TAVR).  Available surgical and transcatheter approaches are limited by high surgical risk, unsuitable septal perforators, and heart block requiring permanent pacemakers.  In a retrospective, single-center study, these investigators reported the initial experience of a novel transcatheter electrosurgical procedure developed to mimic surgical myotomy.  They employed septal scoring along midline endocardium (SESAME) to treat patients, on a compassionate basis, with symptomatic LVOT obstruction or to create space to facilitate TMVR or TAVR.  This trial was carried out between 2021 and 2023; and a total of 76 patients underwent SESAME -- 11 (14 %) had classic HCM, and the remainder underwent SESAME to facilitate TMVR or TAVR.  All had technically successful SESAME myocardial laceration.  Measures to predict post-TMVR LVOT significantly improved (neo-LVOT 42 mm2 [Q1-Q3: 7-117 mm2] to 170 mm2 [Q1-Q3: 95 to 265 mm2]; p < 0.001; skirt-neo-LVOT 169 mm2 [Q1-Q3: 153 to 193 mm2] to 214 mm2 [Q1-Q3: 180 to 262 mm2]; p < 0.001).  Among patients with HCM, SESAME significantly reduced invasive LVOT gradients (resting: 54 mm Hg [Q1-Q3: 40 to 70 mm Hg] to 29 mm Hg [Q1-Q3: 12 to 36 mm Hg]; p = 0.023; provoked 146 mm Hg [Q1-Q3: 100 to 180 mm Hg] to 85 mm Hg [Q1-Q3: 40 to 120 mm Hg]; p = 0.076).  A total of 74 (97.4 %) survived the procedure; 5 experienced 3 of 76 (3.9 %) iatrogenic ventricular septal defects that did not require repair and 3 of 76 (3.9 %) ventricular free wall perforations.  Neither occurred in patients treated for HCM.  Permanent pace-makers were required in 4 of 76 (5.3 %), including 2 after concomitant TAVR.  Lacerations were stable and did not propagate after SESAME (remaining septum: 5.9 ± 3.3 mm to 6.1 ± 3.2 mm; p = 0.8).  The authors concluded that with further experience, SESAME may benefit patients requiring septal reduction therapy for obstructive HCM as well as those with LVOT obstruction after heart valve replacement, and/or could aid in facilitating transcatheter valve implantation.  These researchers stated that data from this initial series suggested that transcatheter myotomy resulted in progressive LVOT remodeling with symptomatic improvement.  They noted that these were pilot observations; further investigations and refinements are needed.

The authors stated that this study had several drawbacks.  First, this was the earliest clinical experience with a new and evolving technique using available commercial guide-wires and catheters outside FDA-approved indications (“off-label”).  Second, SESAME was offered on a compassionate basis to a heterogeneous group of patients with high or prohibitive risk of morbidity and mortality from cardiac surgery, or who declined conventional treatments.  These investigators included all-comers, including many with no therapeutic options or facing impending death.  Such patients are prone to life-threatening complications including stroke and death.  The “phenotypes” are arbitrary and, especially in the case of HCM and “Gradient” groups, probably overlap.  Third, data were collected in the course of medical care; thus, follow-up evaluations were non-systematic and lacked comprehensive follow-up imaging.  Fourth, there was no control or comparator cohort.

Nickenig and Sugiura (2024) noted that the main hurdles to the application of the SESAME procedure include: (i) technical complexity; (ii) expertise of the operator; (iii) lack of dedicated devices; and (iv) optimal patient selection.  Validating the reproducibility of the procedure across different operators is crucial and should be investigated.  Furthermore, the refinement of procedural safety and effectiveness may depend on the development of specialized devices, enabling personalized therapeutic options for each patient.  In addition, the identification of risk factors associated with myocardial complications is important.  Using cardiac magnetic resonance tomography and computed tomography (CT) may be essential for evaluating tissue characteristics and precisely assessing the anatomy and thickness of the septum.  The applicability and feasibility of extending the SESAME procedure to patients with HCM or those with valvular heart disease remains an area yet to be explored.  The authors stated that this new transcatheter electrosurgical technique may fill an unmet clinical need in patients who require LVOT modification; thus, offering a feasible option for patients with HCM and enlarging the field of TMVR and TAVR.

Ueyama et al (2024) stated that SESAME is a transcatheter septal myotomy procedure developed to treat patients with symptomatic LVOT obstruction and to facilitate TMVR or aortic valve replacement.  In the authors’ initial experience with SESAME, they observed that a subset of patients, including those initially undergoing SESAME to enable future TMVR, reported significant symptom improvement following SESAME alone, subsequently opting to defer TMVR.  This study identified specific patient phenotypes that might achieve substantial symptom improvement from SESAME.  Between 2021 and 2023, a total of 76 patients underwent SESAME.  Patients were stratified into 3 groups: HCM with LVOT obstruction, valvular disease with LVOT obstruction, and valvular disease without LVOT obstruction.  A subgroup of patients who underwent SESAME pre-TMVR was also identified and stratified by the presence of LVOT obstruction and the type of mitral valve disease (either predominantly mitral regurgitation [predominantly MR] or mitral stenosis alone [MS]).  Symptom improvement (defined as improvement in NYHA class of 1 or greater at 30 days, prior to TMVR), change in septal thickness (by CT), and change in LVOT peak gradient (by echocardiography) were compared between groups using Fisher’s exact test and Mann-Whitney U test, as appropriate.  In the overall cohort, post-SESAME CT, echocardiography, and 30-day follow-up was available for 44 elective cases.  Among them, those with LVOT obstruction (comprising both HCM and valvular disease with LVOT obstruction: n = 24) had a wider septal thickness at baseline (18.9 [16.2 to 22.3] mm versus 14.9 [13.3 to 16.3] mm, p = 0.001), with larger absolute septal reduction after SESAME (reduced by 13.3 [10.2 to 15.3] mm versus 8.2 [6.9 to 10.7] mm, p = 0.001), and higher LVOT peak gradient at baseline (56.4 [39.7 to 75.6] mmHg versus 19.5 [11.8 to 30.0] mmHg, p < 0.001), with numerically a larger percent reduction after SESAME (reduced by 38.9 [8.8 to 58.9] % versus 17.4 [−10.4 to 56.2] %, p = 0.3) compared to those without LVOT obstruction (valvular disease without LVOT obstruction: n = 20).  These patients had a significant reduction in the incidence of systolic anterior motion (from 37.5 % before to 8.3 % after, p = 0.02) and were more likely to have symptom improvement (NYHA of 1 or greater) after SESAME (79 % versus 45 %, p = 0.029).  A total of 54 patients underwent SESAME to facilitate subsequent TMVR, with the majority having mitral annular calcification (MAC)-related mitral valve disease (81 %).  A total of 16 (30 %) experienced symptom improvement (NYHA of 1 or greater), resulting in the deferral of TMVR.  Patients with baseline LVOT obstruction were more likely to defer TMVR compared to those without LVOT obstruction (10/20 [50 %] versus 6/34 [18 %], p = 0.016).  When patients with baseline LVOT obstruction were further stratified by the type of mitral valve disease, there were similarly high rates of TMVR deferral in both predominantly MR and MS group (5/11 [46 %] versus 5/9 [56 %]; p = 1.0).  Conversely, among those without baseline LVOT obstruction, only the MS alone group showed symptom improvement leading to TMVR deferral (0/24 [0 %] versus 6/10 [60 %]; p < 0.001).  In patients with MS, there was no significant change in trans-valvular mean gradient before and after SESAME (baseline: 12.0 [9.3 to 16.3] mmHg versus post-SESAME: 11.0 [8.5 to 14.5] mmHg; p = 0.25), irrespective of baseline LVOT obstruction.  These researchers stated that the findings of this trial should be interpreted considering its limitations, including its small, retrospective design without adjustment for confounders, and the subjective nature of the NYHA classification.  The authors stated that further prospective studies with complete hemodynamic assessment, including changes in contractile function, diastolic function, as well as volumetry, are needed to elucidate the mechanisms underlying symptom improvement following SESAME.

Chu et al (2025) noted that HCM is a prevalent condition characterized by ventricular hypertrophy, which results in LVOT obstruction in 2/3 of patients.  Traditional pharmacotherapies, including beta-blockers, calcium channel blockers (CCBs) and disopyramide, have been the cornerstone of symptom management but lack disease-modifying effects.  The introduction of cardiac myosin inhibitors as first-line therapy to directly target sarcomeric hypercontractility has dramatically changed clinical practice.  However, several logistical factors presently limit the widespread adoption of cardiac myosin inhibitors, and their long-term side-effects and outcomes require ongoing investigation.  Emerging pharmacological approaches, including EDG-7500 and gene therapies, aim to refine treatment strategies.  For patients with refractory symptoms, invasive septal reduction therapies, including surgical myectomy and alcohol septal ablation, remain critical.  Innovations such as RFA and SESAME offer promising, minimally invasive alternatives.  The authors concluded that as therapeutic options expand, optimizing patient selection, monitoring protocols and long-term outcomes remain crucial in advancing care for patients with obstructive hypertrophic cardiomyopathy.

These researchers stated that the few available studies on SESAME have reported successful reduction of septal thickness, enlargement of the LVOT area and symptom improvement in the majority of patients.  The decline in residual LVOT gradients occurred progressively as septal myotomy continued to widen for at least 1 month post-operatively.  Although initial results were promising, further research is needed to examine the degree of progressive septal splay over a longer follow-up period, as well as the impact of ablation depth on long-term outcomes.  These investigators noted that complication rates of SESAME are high relative to other septal reduction therapies, which is expected considering the early and evolving experience with this technique.  In the largest study on SESAME to date, 30 % of 76 patients experienced a major complication, such as significant bleeding, iatrogenic myocardial perforation or the need for a permanent pacemaker (Greenbaum et al, 2024).  The intra-operative mortality rate was 2.6 %, which is higher than mortality rates of alcohol septal ablation and myectomy at high-volume centers, but comparable to those at lower-volume centers.  The authors stated that SESAME’s high complication rates likely reflect its early stages of development in addition to the technical challenges of the technique.  Adequate training of proceduralists will likely be a barrier to its widespread adoption.

Furthermore, UpToDate reviews on “Hypertrophic cardiomyopathy in children: Management and prognosis” (Ryan and Maron, 2025), “Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction” (Maron, 2025a), and “Hypertrophic cardiomyopathy: Management of ventricular arrhythmias and sudden cardiac death risk” (Maron, 2025b) do not mention SESAME (SEptal Scoring Along the Midline Endocardium) as a management / therapeutic option / tool.

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Glossary of Terms 

Table: Glossary of Terms

Term	Definition
Hypertrophic Cardiomyopathy	A disease in which the heart muscle becomes thickened (hypertrophied), making it hard for the heart to pump blood
New York Heart Association (NYHA) Classification	Provides a way to classify the extent of heart failure; a tool used for risk stratification which classifies patients in one of four categories based on their limitations during physical activity, limitations/symptoms in regards to normal breathing, varying degrees in shortness of breath and or angina pain
Percutaneous	Passing through the skin
Transluminal	Passing across or performed by way of a lumen of a blood vessel

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Appendix 

Table: New York Heart Association (NYHA) Classification

Class	Classification
Class I	Patients with cardiac disease but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain.
Class II	Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.
Class III	Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain.
Class IV	Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.

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References