Mitral Transcatheter Edge-to-Edge Repair in Non-Surgical Candidates with Hypertrophic Obstructive Cardiomyopathy: Clip It, or Ablate It?

Abstract

Hypertrophic cardiomyopathy (HCM), with or without obstructive phenomena, remains underdiagnosed and undertreated. This condition often involves pathological changes in the mitral valve leaflets and apparatus, which can lead to relevant mitral regurgitation (MR). The mechanism of MR is mostly related to the systolic anterior motion (SAM) of the anterior mitral leaflet. The treatment of patients with hypertrophic obstructive cardiomyopathy (HOCM) with persistent symptoms despite optimal pharmacological therapy includes septal myectomy or transcoronary ablation of septal hypertrophy (TASH). Percutaneous edge-to-edge repair of the mitral valve represents an innovative alternative therapy with promising results regarding clinical symptoms and echocardiographic findings. In this article, we provide a concise, critical overview of the current evidence on this technique in HOCM and delineate future perspectives and unresolved issues.

1. Introduction

Hypertrophic cardiomyopathy (HCM) is an inherited cardiomyopathy with a prevalence of approximately 1:500 and is characterized by left ventricular hypertrophy, typically diagnosed using two-dimensional echocardiography or cardiac magnetic resonance imaging [1]. A subgroup of HCM patients presented with a dynamic left ventricular outflow tract (LVOT) obstruction, at rest in 30% and after provocation in an additional 30% [2,3]. The most common symptoms of HCM patients are dyspnea, syncope, and palpitations, although malignant arrhythmia leading to sudden cardiac death can be the first manifestation of the disease [4]. The subtype of HCM with obstructive phenomena has a higher rate of heart failure progression compared with the non-obstructive subtype [4].

In symptomatic patients with obstructive HCM, the European Society of Cardiology guidelines recommend, as first-line treatment (I Class, B Level), a non-vasodilating beta-blocker or verapamil (in patients who are intolerant to or have contraindications to beta-blockers), or, in addition, disopyramide [5]. In patients with persistent symptoms despite the maximum tolerated doses, the addition of mavacamten (a cardiac myosin ATPase inhibitor) is recommended (IIa Class, A Level) [5]. Based on current guidelines, surgical myectomy or transcoronary ablation for septal hypertrophy (TASH) (I Class, B Level) is considered the preferred invasive septal reduction therapy for patients with hypertrophic obstructive cardiomyopathy (HOCM) who remain symptomatic [5,6].

Mitral regurgitation (MR) is commonly observed in patients with HOCM (Figure 1). In most cases, MR results from the secondary to systolic anterior motion (SAM) of the anterior mitral leaflet, which is associated with dynamic outflow tract obstruction and is typically characterized by a posteriorly directed jet [7]. However, MR in HOCM is not solely associated with SAM, and other mechanisms may also be involved. The presence of more centrally or anteriorly directed regurgitation jets should be a red flag, indicating additional mitral valve pathology beyond SAM [7]. The mitral valve apparatus and its substructures, such as anterior displacement of the papillary muscles, abnormal secondary chordae attachment to the anterior mitral leaflet, and elongated redundant leaflets, can contribute to failed TASH and promote further LVOT obstruction [8,9]. Moreover, significant primary MR caused by mitral valve chordal rupture or prolapse, as a concurrent mitral valve disease in HOCM patients, is a rare finding, occurring in 1% of the HCM population. This should not be overlooked and may require a completely different interventional approach [10]. Mitral annular shape, size, angulation, and function can also be assessed by 3D echocardiography and cardiac magnetic resonance imaging in patients with HOCM [11,12,13]. These patients exhibit mitral annular dilatation and reduced fractional shortening compared to control subjects. Moreover, posterior mitral annulus or leaflet calcification is a common finding in patients with HOCM due to mechanical stress on the mitral annulus [11,12,13].

The mitral transcatheter edge-to-edge repair (M-TEER) in HOCM patients represents an area of growing interest, particularly for patients who are not candidates for established septal reduction therapies and who have failed TASH or surgical myectomy. Our manuscript is descriptive rather than analytical. It reflects the limited number of randomized studies and aims to evaluate the emerging role of this treatment while identifying gaps in the current evidence, especially in comparison with established septal reduction therapies. Nevertheless, we have detailed this topic and proposed an algorithm that we believe will be valuable for cardiologists and interventionalists who are exploring this approach.

2. Mitral Transcatheter Edge-to-Edge Repair in HOCM Patients

M-TEER is a well-established treatment for mitral valve disease [14]. According to guidelines from the European Society of Cardiology, M-TEER should be considered in selected symptomatic patients with chronic severe atrial secondary MR who are not eligible for surgery, despite optimal medical treatment and meeting the echocardiographic eligibility criteria, with II B level, class B [15].

A new off-label application of M-TEER may be for patients with HOCM. In 2014 Schäfer and colleges described for the first time a meaningful reduction of LVOTO related to SAM after M-TEER [15,16]. Unfortunately, the number of cases and long-term outcome data on the use of M-TEER as an interventional approach in HOCM are limited. The narrowing of the LVOT mainly depends on the degree of septal hypertrophy, but it is also influenced by the mitral valve apparatus, particularly the redundant anterior mitral leaflet and its abnormal movement. In HOCM, M-TEER may functionally mimic surgical anterior leaflet plication by restricting leaflet mobility and shifting the coaptation zone posteriorly, thereby reducing SAM and LVOT obstruction. In our view, M-TEER might be a safer or more effective option for patients who are poor surgical candidates, either as a stand-alone alternative or as an adjunctive therapy to TASH. The patient’s anatomical suitability for percutaneous edge-to-edge repair is a key factor when considering M-TEER as an alternative treatment option in patients with HOCM.

The disadvantages of TASH, compared to M-TEER, include the risk of cardiac conduction abnormalities that may require a pacemaker or lead to life- threatening arrhythmias or even sudden cardiac death, especially on the substrate of infarcted myocardium [17,18]. The risk of complete atrioventricular block (AV block) after TASH is 10–20%, and one in three patients will develop right bundle branch block (RBBB) [19,20]. A newly detected RBBB in a patient with pre-existing left bundle branch block (LBBB) can significantly increase the risk of complete cardiac block. Clip-associated conduction abnormalities are rare in non-HCM patients with severe MR. Eggebrecht et al. reported a 0.2% incidence of permanent pacemaker implantation following MitraClip, without detailed information on the underlying indications [21]. In a meta-analysis, Wang et al. found no significant need for pacemaker implantation, whereas Schnitzler et al. did not consider it a noteworthy complication [22,23]. Obviously, there are no relevant details in HOCM patients after M-TEER procedures. If data support that M-TEER can be performed in these patients without the need for a permanent pacemaker, it would be reasonable to consider the method as a first-line approach instead of TASH for patients at risk of pacemaker implantation. Additionally, in non-HCM patients, sudden cardiac death or life-threatening ventricular arrhythmias appear to be uncommon after MitraClip implantation, based on a systematic review by Cameron et al. published in Heart, Lung and Circulation [24]. A meta-analysis of five studies involving patients undergoing MitraClip who reported ventricular arrhythmia rates before and after the procedure showed a significant reduction in ventricular arrhythmias, non-sustained VT, and VT/VF [24]. These findings support the hypothesis that correcting MR, which reduces mechanical cardiac stress, may help lower the risk of sudden cardiac death [24]. Nevertheless, there remains a residual risk of life- threatening arrhythmias, largely influenced by patient-specific factors such as advanced age, reduced ejection fraction, elevated EuroScore, end-stage renal disease, pulmonary hypertension, and atrial fibrillation [25]. Importantly, current evidence on ventricular arrhythmias following MitraClip is limited, underscoring the need for larger, well-designed studies. Clearly, there is no available data on the risk of SCD in HOCM patients after MR repair with M-TEER. LVOT thickness for TASH is generally considered to be greater than 17 mm to ensure a safe procedure and minimize the risk of iatrogenic ventricular septal rupture. In contrast, basal septal thickness greater than 25 mm is a predisposing factor for TASH failure [26,27]. Septum hypertrophy measuring about 15–17 mm is a more borderline anatomy, indicating the need for alternative septal reduction therapy [26,27]. The inability to identify a target septal branch occurs in up to 10% of TASH patients and should also be considered an important factor in procedural planning [28]. From our perspective, unsuitable LVOT geometry, coronary septal branch anatomy, or pre-existing bundle branch block make M-TEER a more favourable therapeutic strategy, especially in patients with SAM. It should be highlighted that M-TEER is more appropriate for patients with significant MR who present with a more dynamic LVOTO, than for patients with LVOT narrowing due to significant left ventricular hypertrophy.

Another important aspect is the management of HOCM patients after failed TASH. Redo TASH is required in approximately 6.6% of patients, and surgical myectomy is performed in 1.9% to address persistent symptoms [29,30]. Importantly, perioperative mortality of surgical myectomy after failed TASH is substantially higher (6%) than in matched patients undergoing septal myectomy as the first and only treatment [31]. In this challenging clinical setting, M-TEER applied within the SESAME (septal reduction by edge-to-edge repair and systolic anterior motion elimination) concept may represent a potential alternative for carefully selected patients who are not candidates for redo TASH, while avoiding the need for high-risk surgical myectomy [32,33]. However, SESAME is a novel, technically demanding approach, currently supported only by limited case-based experience, and should therefore be restricted to rare, highly selected HOCM patients treated at specialized expert centers. In addition, in the presence of concomitant primary mitral valve disease, an M-TEER-based strategy may allow simultaneous treatment of both pathomechanisms, namely SAM-related LVOT obstruction and primary MR, within a single procedure. Therefore, M-TEER may be a game changer for patients with failed TASH who are ineligible for redo TASH, while also avoiding the need for high-risk procedures like surgical myectomy or SESAME after failed TASH. Furthermore, the presence of relevant concomitant primary mitral valve disease can be considered when choosing M-TEER over TASH as a first-line treatment, thereby targeting both pathomechanisms in a single procedure: first, SAM with LVOT obstruction; and second, the component of primary MR.

In conclusion, the following clinical factors may even support considering M-TEER instead of TASH as a primary therapeutic option (Figure 2): 1. lower risk of conduction abnormalities or pacemaker implantation, especially in high-risk patients with previous LBBB; 2. suitability for patients with septal hypertrophy of less than 15–17 mm; 3. patients who lack a suitable septal branch or have unfavorable LVOT geometry for TASH; 4. presence of relevant concomitant primary mitral valve disease; or 5. previous unsuccessful TASH.

3. Clinical Evidence for M-TEER in HOCM

Schäfer and colleagues reported, for the first time, the successful use of M-TEER in HOCM patients in 2014 and 2015. They treated three HOCM patients with MitraClip, resulting in improvements in rest peak gradients (before M-TEER: 65 ± 25.5 mmHg; after M-TEER: 7.7 ± 5.0 mmHg) and provoked pressure gradients (before M-TEER: 145.3 ± 8.1 mmHg; after M-TEER: 23.2 ± 7.6 mmHg) [16]. One of these patients had previously undergone a Morrow operation and mitral valve reconstruction, and another had previous TASH. The clinical and hemodynamic improvements were observed at a six-week follow-up [16]. These initial findings supported M-TEER as a viable option after failure of standard septal reduction therapies. Additionally, Kimmelstiel et al. observed a reduction in cardiac workload, assessed by pressure–volume loops, after successful M-TEER intervention in two patients with symptomatic HOCM who were not candidates for standard septal reduction therapies [34].

Sorajja et al. reported early success in HOCM patients who underwent MitraClip for symptom relief, MR, and LVOT reduction, with consistent results observed during the follow-up period (10–19 months) [35]. Eight years ago, Thomas et al. analyzed the beneficial role of M-TEER improving symptoms and hemodynamics in 15 HOCM patients with SAM across four studies [36]. Generally, M-TEER was adopted as the first-line strategy, with only one patient having failed a previous surgical myectomy and another failing an ASA attempt [36]. He also demonstrated elimination of SAM, a reduction in MR grade, and a significant decrease in the LVOT gradient from a mean of 75.8 ± 39.7 to 11.0 ± 5.6 mm Hg. After reviewing these two publications, M-TEER represents a valuable ‘arrow’ in our ‘quiver’ as a first-line approach [36].

Recently, Mascarenhas et al. published a patient-level meta-analysis after reviewing nineteen publications involving 37 HCM patients who underwent edge-to-edge repair of the mitral valve [37]. M-TEER not only reduced LVOT obstruction phenomena (the mean peak resting and provoked LVOT gradient: 69.2 ± 40.3 mmHg vs. 11.7 ± 8.6 mmHg and 98.2 ± 53.4 mmHg vs. 14.1 ± 13.9 mmHg, respectively) but also decreased the median MR grade (4.0 [3.0–4.0] vs. 1.0 [1.0–1.0]) [37]. The echocardiographic improvements were accompanied by a clinical improvement in NYHA functional class, from 3 to 1 (post-TEER: 100% vs. 7%; all p < 0.001) [37].

The decision to perform M-TEER versus TASH or myectomy, based on the evidence of isolated cases in

Table 1. Baseline characteristics.

Case	Age	Gender	EuroScore	NYHA	LVOT Obstruction: Resting Gradient, Provoked Gradient	IVSD	SAM	MR (Grade)	Medical Treatment	Previous Treatment
U. Schaefer [16], Case 1	69	Male	15.80%	III	36 mmHg, 136 mmHg	19 mm	Yes	Severe	Beta-blocker	Morrow and MVR two years before
U. Schaefer [16], Case 2	78	Female	30.30%	IV	75 mmHg, 155 mmHg	21 mm	Yes, but also mid-ventricular	Severe	Verapamil	TASH 6 months before
U. Schaefer [16], Case 3	76	Male	7.60%	III	84 mmHg, 145 mmHg	24 mm	Yes	Severe	Verapamil	PCI of LCMA with stent crossing the first septal branch
C. Kimmelstein [34], Case 1	68	Male	n.a.	III	39 mmHg, 88 mmHg	n.a.	Yes	Moderate to severe	Yes, n.a.	Failed TASH attempt (septal jailed with previous stent)
C. Kimmelstein [34], Case 2	66	Male	n.a.	III	80 mmHg, n.a.	n.a.	Yes	Severe	Yes, n.a.	Not suitable coronary anatomy
P. Sorajja [35], Case 1	87	Female	n.a.	III	61 mmHg, n.a.	18 mm	Yes	Severe	Negative inotropic agents	No
P. Sorajja [35], Case 2	90	Female	n.a.	III	44 mmHg, 81 mmHg	16 mm	Yes	Severe	Negative inotropic agents	No
P. Sorajja [35], Case 3	75	Male	n.a.	III	20 mmHg, 100 mmHg	17 mm	Yes	Severe	Negative inotropic agents	No
P. Sorajja [35], Case 4	72	female	n.a.	III	144 mmHg, not performed	23 mm	Yes	Severe	Negative inotropic agents	No
P. Sorajja [35], Case 5	89	Female	n.a.	III	36 mmHg, 92 mmHg	18 mm	Yes	Massive	Negative inotropic agents	No
A. Long [38], Case 1	72	Female	n.a.	III-IV	n.a., 94 mmHg	n.a.	Yes	Moderate to severe	Verapamil	No
A. Al Turk [39], Case 1	82	Male	n.a	n.a.	Not relevant, 120 mmHg	n.a.	Yes	Severe	n.a.	No
U. Schaefer [40], Case 1	69	Male	(logEUROscore 15.8%)	II-III	59–83 mmHg, >150 mmHg	n.a	Yes	Severe	n.a.	Surgical myectomy and mitral ring annuloplasty
S. Gupta [41], Case 1	76	Male	n.a.	III	74 mmHg (unknown if rest or provoked)	20 mm	Yes	Severe	n.a.	No
S. Gupta [41], Case 2	45	Male	n.a.	IV	85 mmHg (unknown if rest or provoked)	23 mm	Yes	Severe	n.a.	No
S. Gupta [41], Case 3	81	Female	n.a	III	130 mmHg (unknown if rest or provoked)	14 mm	Yes	Severe	n.a.	No
M. Coylewright [42], Case 1	84	Female	n.a.	II-III	20 mmHg, > 40 mmHg	n.a.	Yes	Severe, prolapse p2	n.a.	No
D. Harrison [43], Case 1	26	Male	n.a.	IV	95 mmHg, n.a.	n.a.	Yes	Severe	n.a.	Surgical myectomy
N. Wong [44], Case 1	76	Female	7.64%	III	76 mmHg, n.a.	23 mm	Yes	Severe (Flail P2)	Verapamil and beta-blocker	No
X. Huang [45], Case 1	68	Female	n.a.	II-III	107 mmHg (unknown if rest or provoked)	15.2 mm	Yes	Severe (degenerative A2/A3)	n.a.	No
J. Rezkalla [46], Case 1	71	Male	n.a.	II-III	n.a., 150 mmHg (dobutamine)	n.a.	Yes	Dynamic severe	Beta-blocker	TASH (2015), surgical myectomy (2021)
O. Rabi [47], Case 1	53	Female	n.a.	IV	154 mmHg (unknown if rest or provoked)	24 mm	Yes	Severe	Beta-blocker	No
C. Bourque [48], Case 1	68	Male	n.a.	III	40 mmHg (unknown if rest or provoked)	n.a.	Yes, acute	Severe dynamic annular dilatation	n.a.	No
A. Pantazis [49], Case 1	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Moderate to severe	n.a.	n.a.
A. Pantazis [49], Case 2	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Severe	n.a.	n.a.
A. Pantazis [49], Case 3	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Severe	n.a.	n.a.
A. Pantazis [49], Case 4	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Moderate to severe	n.a.	n.a.
A. Pantazis [49], Case 5	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Severe	n.a.	n.a.
A. Pantazis [49], Case 6	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Moderate to severe	n.a.	n.a.

IVSD: intraventricular septal interventricular septum thickness at end-diastole, LCMA: left coronary main artery, LVOT: left ventricular outflow tract, MR: mitral regurgitation, MVR: mitral valve reconstruction, n.a.: not available, PCI: percutaneous coronary intervention, NYHA: New York Heart Association, SAM: systolic anterior motion, TASH: transcoronary ablation of septal hypertrophy.

, was supported by the clinical conditions of the patients (such as previous aortocoronary bypass surgery and stage IV cirrhosis), anatomical features (including prior TASH, Morrow operation, or jailed septal branch with stent), and the decision of the heart team, considering high perioperative risk, comorbidities, increased age, and frailty. After analysing the baseline characteristics (Table 1), most patients had severe symptomatic MR (NYHA III) with concurrent SAM, despite being on negative inotropic pharmacologic treatment. The median age was 71 years. Six of the 29 patients (20%) had previously undergone a Morrow or TASH attempt. A subgroup analysis comparing outcomes, pooled insights, and complications is unattainable due to the small number of cases and varying baseline characteristics, as the data are predominantly from case reports. In our view, the manuscript highlights that M-TEER was safe, feasible, and effective without major complications. A deeper subgroup analysis would still not provide properly powered data or reliable results. According to published data, most patients with HOCM underwent MitraClip implantation rather than the PASCAL device. Possible reasons for preferring the MitraClip system include its broader worldwide availability and longer data history, as well as more extensive anterior-to-posterior mitral leaflet plication, causing more leaflet tension. Most patients treated with MitraClip showed clinical improvement, along with echocardiographic reduction in MR and a decrease in the resting LVOT gradient during follow-up (

Table 2. Post MitraClip.

Case	MR Grade	MV Gradient	LVOT Gradient	Follow Up	Asystole, Av Block	Pacemaker/AICD
U. Schaefer [16], Case 1	Trace	5 mmHg	3 mmHg	Six weeks later: trace MR, reduced LVOT gradient, NYHA I-II	No	No
U. Schaefer [16], Case 2	Trace	3 mmHg	7 mmHg	Six weeks later: trace MR, reduced LVOT gradient, NYHA I-II	No	No
U. Schaefer [16], Case 3	Trace	3 mmHg	13 mmHg	Six weeks later: trace MR, reduced LVOT gradient, NYHA I-II	No	No
C. Kimmelstein [34], Case 1	Trace	3 mmHg	No obstruction	1 and 2 months later: NYHA I	No	No
C. Kimmelstein [34], Case 2	Trace	4 mmHg	No obstruction	1 and 2 months later: NYHA I	No	No
P. Sorajja [35], Case 1	Mild	6 mmHg	17 mmHg	19 months later: mild MR, PGmean 8 mmHg, Vmax 5.2 m/s, NYHA II	No	No
P. Sorajja [35], Case 2	Mild	2 mmHg	3 mmHg	16 months later: trace MR, PGmean 3 mmHg, Vmax 0.8 m/s, NYHA I	No	No
P. Sorajja [35], Case 3	Trace	3 mmHg	13 mmHg	12 months later: trace MR, PGmean 3 mmHg, Vmax 5.1 m/s, NYHA I	No	No
P. Sorajja [35], Case 4	Mild	4 mmHg	10 mmHg	16 months later: mild MR, PGmean 5 mmHg, Vmax. 6.2 m/s, NYHA II	No	No
P.Sorajja [35], Case 5	Mild	3 mmHg	16 mmHg	10 months later: mild MR, PGmean 3 mmHg, Vmax. 1.9 m/s, NYHA I	No	No
A. Long [38], Case 1	Mild	5 mmHg	27 mmHg	1 month later: mild MR, PGmean 5 mmHg, LVOT gradient at rest/provoked 27 mmHg, no evidence of SAM	No	No
A. Al Turk [39], Case 1	Trace	n.a.	<5 mmHg	n.a. symptom resolution	No	No
U. Schaefer [40], Case 1	Mild	3 mmHg	No obstruction	12 months later: mild MR, no relevant gradient, NYHA I	No	No
S. Gupta [41], Case 1	Mild	5 mmHg	13 mmHg	n.a.	No	No
S. Gupta [41], Case 2	Mild	4 mmHg	12 mmHg	n.a.	No	No
S. Gupta [41], Case 3	Mild	4 mmHg	10 mmHg	n.a.	No	No
M. Coylewright [42], Case 1	Moderate	6 mmHg	No obstruction	n.a.	No	No
D. Harrison [43], Case 1	Moderate	n.a.	10 mmHg	n.a.	No	No
N. Wong [44], Case 1	Mild to moderate	n.a.	33 mmHg	1 and 6 months later: moderate MR, LVOT gradient 38 mmHg, symptoms improved	No	No
X. Huang [45], Case 1	Trace	n.a.	13 mmHg	n.a.	No	No
J. Rezkalla [46], Case 1	Mild	5 mmHg	Complete resolution	1 month later: no MR, without LVOT Gradient, NYHA I	No	No
O. Rabi [47], Case 1	Reduced	n.a.	90 mmHg	1 month later: moderate to severe MR, PGmean 7 mmHg, LVOT gradient 29 mmHg, NYHA I-II	No	No
C. Bourque [48], Case 1	Moderate	n.a.	n.a.	6 months later: MR mild, symptoms improved	No	Yes
A. Pantazis [49], Case 1	Mild	n.a.	n.a.	12 months later: no MR recurrence	No	No
A. Pantazis [49], Case 2	Moderate	n.a.	n.a.	12 months later: no MR recurrence	No	No
A. Pantazis [49], Case 3	Moderate to severe	n.a.	n.a.	1 month later: MR recurrence	No	No
A. Pantazis [49], Case 4	Mild	n.a.	n.a.	8 months later: MR recurrence	No	No
A. Pantazis [49], Case 5	Mild	n.a.	n.a.	12 months later: no MR recurrence	No	No
A. Pantazis [49], Case 6	Mild	n.a.	n.a.	12 months later: no MR recurrence	No	No

AICD: automatic implantable cardioverter-defibrillator, Av-block: atrioventricular block, LVOT: left ventricular outflow tract, MR: mitral regurgitation, MV: mitral valve, n.a.: not available, NYHA: New York Heart Association.

). Extensively, the MR was quantified as trace, mild, or moderate in 28 of 29 patients, with only one patient having moderate to severe MR postprocedurally. Recurrence of MR occurred in only two cases. Regarding high-grade AV block or life-threatening arrhythmias, the rate was zero. No severe procedure-related complications were observed. LVOT gradients after the procedure were significantly reduced and remained consistently low on follow-up. Particularly, three cases had gradients above 20 mmHg and below 50 mmHg, and only two patients experienced extreme high gradients. In seven cases, no data were stated. The remaining patients, about 17, showed very low LVOT gradients.

The manuscript summarizes isolated cases or small case series in our Table 1 and Table 2. It is very challenging to compare individual cases and discuss biases due to the absence of randomized studies. Clearly, the current critical appraisal is difficult and limited to isolated cases. Designing randomized studies that compare the two strategies—M-TEER versus TASH—in HOCM patients who are not surgical candidates would be helpful. Such studies would raise the level of evidence and clarify the roles and scopes of each approach.

4. Selection of Percutaneous Strategies for HOCM Patients with MR

The percutaneous edge-to-edge repair of the mitral valve appears to be an alternative treatment option for patients who are not candidates for surgery or belong to a high surgical-risk group, especially those with a significantly increased LVOT gradient and SAM, and favorable anatomy for classical TASH treatment.

The hemodynamic success rate after TASH is reported to be 70%, with 20% of those patients experiencing severe symptoms due to residual obstruction, which may require another septal reduction therapy in the range of 15–18% [32,50]. The re-operation rate following septal myectomy, as documented below, is under 2% [50]. Valeti et al. also showed that up to 25% of patients undergoing TASH had a residual LVOT gradient on postprocedural cardiac magnetic resonance imaging, attributable to sparing of the basal septum [51]. At this point, the possibility of redoing the TASH or SESAME based on echocardiographic and anatomical criteria should be considered, as should the determination of which component—SAM-associated MR or the LVOT gradient—is primarily responsible for the patient’s symptoms.

HOCM patients can be classified by the severity of obstruction at rest or after provocation, with this classification correlating with long-term cardiovascular events [52]. Patients with resting or provoked LVOT gradients above 30 mmHG, or resting LVOT gradients below 30 mmHg but a gradient of ≥90 mmHG after provocation, are considered a high-risk cohort with clear clinical therapeutic implications [53]. Furthermore, MR severity in HOCM patients should be thoroughly quantified based on echocardiographic criteria before decision-making, with initial treatment of MR using M-TEER against TASH [52,53]. It is questionable whether the standard criteria [53], with an effective regurgitant orifice area ≥0.4 cm², an MR volume of 60 mL, and a regurgitant fraction above 50% define severe MR, as opposed to moderate MR, which is characterized by an effective regurgitant orifice between 0.2–0.39 cm², MR volume of 30–59 mL, and a regurgitant fraction between 30–49%, should be applied for the utilization of M-TEER against TASH [53]. In cases with a proportionate MR (moderate to severe) relative to the degree of LVOT gradient (at least 30 mmHG at resting or more than 90 mmHg after provocation) and the presence of a septal branch as an additional target, current literature would support a redo TASH over M-TEER. Conversely, a disproportional relationship between significant MR (severe) and the LVOT gradient (maximal 30 mmHg or provoked gradient <90 mmHg) favours adopting M-TEER rather than redoing TASH. Diagnostic assessment can be quite complex in most patients because LVOT obstruction is dynamic (often related to SAM). The cornerstone is to detect signs of dynamic LVOT obstruction, especially using high positive Brockenbrough–Braunwald–Morro signs.

We propose dividing HOCM patients into three most commonly documented scenarios (Figure 3), which are as follows:

A.

HOCM and mild mitral valve redundancy and significant LVOT hypertrophy with favourable anatomy for TASH

This type of obstruction almost always occurs with midcavity obstruction (also called midventricular obstruction) and is reported in 10–15% of patients with HCM. TASH remains the preferred approach in symptomatic patients despite optimal medical therapy, when coronary and septal anatomy are favourable, as recommended by guidelines.

B.

HOCM with SAM (irrespective of MR severity) and LVOTO without significant septal hypertrophy and without a favourable anatomy for TASH

If there is a significant SAM phenomenon (with or without a redundant anterior mitral leaflet) combined with a mitral valve area exceeding 3.5–4 cm², borderline LVOT hypertrophy, and not suitable coronary anatomy, primary M-TEER might be advantageous. This procedure can help lower the LVOT gradient and reduce MR.

C.

HOCM with SAM-related MR and predominantly significant primary, mixed, or secondary MR

In our view, M-TEER emerged as a reasonable approach for patients with HOCM or those with hypertensive heart disease and concurrent primary mitral valve disease before performing TASH. In this cohort, those who develop a flail leaflet or mitral valve prolapse while in a long-term, stable anatomical and hemodynamic HOCM state will benefit from M-TEER, with TASH playing a complementary role in persistent symptoms.

If the primary mechanism of MR is the SAM with a high LVOT gradient, proceeding with TASH in patients with suitable coronary anatomy is appropriate. A stepwise approach, such as M-TEER, can be considered and implemented after a successful TASH, particularly when the LVOT gradient and SAM are eliminated, but moderate-to-severe secondary MR persists (Figure 4 and Figure 5). From our point of view, M-TEER should be considered as first-line treatment in the subgroup of patients suffering from coexisting severe secondary MR and disproportional lower LVOTO (maximal 30 mmHg or provoked gradient under 90 mmHg). If the LVOT gradient persists after M-TEER, TASH should be adopted to treat the remaining obstructive phenomena.

The choice between TASH and M-TEER should be tailored to the individual patient’s left ventricular morphology, considering echocardiographic and anatomical factors characteristics. When the cause of symptoms is unclear, and a complex, mixed mitral valve disease is present, a combined staged approach using both TASH and M-TEER may be beneficial for the patient’s symptoms. This strategy not only alleviates symptoms but also improves the patient’s hemodynamic status. Most patients with HOCM who underwent edge-to-edge repair benefited in terms of symptoms, and this was associated not only with MR reduction but also with near-complete elimination of the LVOT gradient. This alternative appears to work relatively well. According to published data, none of the patients underwent TASH after M-TEER, supporting this approach as relatively efficient. Nevertheless, it should keep the door open to using TASH in post–M–TEER patients with a significant residual LVOT gradient. A direct comparison study between M-TEER and TASH has not yet been conducted. More data are needed to answer key questions: which HOCM patient profile might benefit most from M-TEER; whether combining TASH and M-TEER offers superior results compared to monotherapy; when monotherapy is sufficient; what should be the first- and second-line percutaneous treatments; and how the LVOT gradient and mitral regurgitation behave over the long term in HOCM patients treated initially with M-TEER alone.

5. Conclusions

Extensive experience with TASH suggests it is a first-line treatment for patients with HOCM and mild intrinsic mitral valve disease, especially SAM-related cases, rather than for those with a redundant anterior mitral leaflet or mild primary or secondary MR. M-TEER can be used as an alternative treatment for well-selected patients with HOCM, without primarily addressing the septal hypertrophy. A careful functional and anatomical assessment using transthoracic and transesophageal echocardiography, or even cardiac magnetic resonance imaging, is essential for identifying redundant anterior mitral valve leaflet. It should be emphasized that the presence of mitral valve redundancy can be the major pathomechanism of SAM-related mitral regurgitation and resultant obstruction, which can be targeted by primary M-TEER. M-TEER could eventually be incorporated into our treatment options for patients with borderline septal hypertrophy, severe primary or secondary MR, previous TASH failure, conduction abnormalities, absence of a suitable culprit septal branch, and echocardiographic features appropriate for M-TEER.

M-TEER is currently used off-label for patients with HOCM, with encouraging and promising results, although the available data come from case reports. Our enthusiasm for this no-touch septal technique should be supported subsequently by randomized controlled studies before it is adopted into our routine clinical practice.