Hypertrophic cardiomyopathy (HCM) is a genetic disorder with a prevalence of 1 in 200 to 500, a heterogeneous phenotypic expression, and a widely variable clinical course [1, 2]. It is characterized by left ventricular (LV) wall thickening and hypertrophy, which is often in an asymmetric pattern and may be associated with abnormalities of the mitral valve (MV) and subvalvular apparatus [3]. Approximately 70% of HCM patients have left ventricular outflow tract (LVOT) obstruction secondary to LV hypertrophy, anatomic narrowing of the LVOT, and systolic anterior motion (SAM) of the MV [4, 5, 6]. As a result, patients present with dyspnea, angina, or syncope, and significant mitral regurgitation is a common co-morbidity [3, 7].

Individuals with symptomatic obstructive HCM on maximally-tolerated guideline-directed medical therapy may undergo septal myectomy to relieve LVOT obstruction, reduce heart failure symptomatology, and improve quality of life [8, 9]. Concomitant MV surgery is considered in cases of valvular pathology, severe SAM with residual LVOT obstruction, or significant mitral regurgitation (MR). One approach is the performance of an edge-to-edge MV repair (‘Alfieri stitch’) which approximates the anterior and posterior leaflets at their A2 and P2 scallops, respectively [10]. This anchors the MV coaptation point more central in the LV cavity and limits anterior leaflet excursion into the LVOT, thereby reducing SAM. While use of the edge-to-edge MV repair in primary and secondary MR has been well described, the literature regarding outcomes in obstructive HCM are less robust [11, 12, 13, 14].

In the present systematic review, we sought to assess the published studies on combined septal myectomy and edge-to-edge MV repair for patients with refractory obstructive HCM, with a focus on echocardiographic and clinical outcome measures.

In the present systematic review of septal myectomy plus edge-to-edge MV repair for obstructive HCM, the following findings were observed at an early to mid-term follow-up of 2.8 years: (1) the classic or modified Morrow technique was performed for septal myectomy, and nearly all edge-to-edge MV repairs were completed without an annuloplasty ring; (2) there were significant reductions in the peak LVOT gradient, interventricular septal wall thickness, and moderate or greater MR, with elimination of SAM in all patients; (3) while there was a decrease in the LV ejection fraction, there was favorable chamber geometry as evidenced by a stable LV internal diastolic diameter; and, (4) clinical outcomes were quite satisfactory, with a survival rate of 97%, re-operative MV surgery in 2%, persistent New York Heart Association functional class III/IV heart failure symptoms in 3%, and permanent pacemaker implantations in 6%.

Septal myectomy using the classic Morrow technique was introduced in 1968 and involves resection of the basal interventricular septum, which allows for an increase in the LVOT diameter; however, there is risk of residual SAM due to persistent abnormal flow vortices or MV apparatus geometry, particularly in patients with more extensive hypertrophy [26, 27, 28]. In the modified Morrow technique, the resection is extended to the mid-ventricular level distal to the point of anterior MV leaflet-septal contact [24, 25]. This results in a larger streamlined LVOT and avoidance of residual septal bulging, with improvement in symptoms and a long-term survival commensurate to the age and sex-matched general population [29]. Nevertheless, registry data has reported a variable risk of persistent SAM or MR after myectomy alone, particularly in the presence of intrinsic MV apparatus abnormalities [30, 31]. In a study by the Cleveland Clinic group of 115 patients with HCM and MV disease, MV pathology included restrictive leaflets (70%), elongated leaflets (56%), degenerative changes (31%), myxomatous disease (20%), papillary muscle abnormalities (20%), and restrictive chordae (19%) [32]. Over a third of the patients in the present study had elongated anterior MV leaflets, and a small group had papillary muscle pathology. Thus, the European Society of Cardiology recommendations for MV surgery in HCM include: (1) symptomatic patients with an LVOT gradient $\ge$50 mmHg and moderate-to-severe MR not caused by SAM (class IIa, LOE C); and, (2) patients with an LVOT gradient $\ge$50 mmHg and septal thickness $\le$16 mm, or persistent moderate-to-severe MR after myectomy (class IIb, LOE C) [9]. The American Heart Association/American College of Cardiology recommend a reserved approach to MV surgery in HCM for patients with intrinsic MV disease, papillary muscle abnormalities, or abnormal leaflet morphology, in centers for HCM excellence [8]. Importantly, a class III (LOE B) recommendation is given to the use of MV replacement as the primary treatment of LVOT obstruction.

The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database cites a 34% incidence of concomitant MV surgery during myectomy for obstructive HCM in the United States, of which 60% are repairs and 40% replacements [33]. It is notable that concomitant myectomy and MV surgery is associated with a higher morbidity and mortality when compared with myectomy alone (odds ratio [OR] 1.81, 95% Confidence Interval [CI] 1.39–2.36), with MV replacement conferring a higher adjusted composite risk than repair (OR 2.21, 95% CI 1.55–3.16 vs 1.61, 95% CI 1.18–2.18). When performing MV repair in the setting of septal myectomy for obstructive HCM, utilization of the edge-to-edge technique offers several advantages. It is a straightforward repair technique that is reproducible, and adds a relatively small amount of time to the duration of cross-clamping and cardiopulmonary bypass [10]. The A2 and P2 scallops of the MV are well seen through the aortic valve orifice which avoids the necessity for an atriotomy, and limits surgical dissection and trauma to the mitral valve [34]. The latter point is salient, as a transmitral myectomy requires incision and dissection of the anterior mitral leaflet to expose the interventricular septum and subvalvular apparatus, which then requires surgical repair. Nevertheless, a transmitral approach to myectomy followed by edge-to-edge repair can be applied if it is preferred or indicated. The primary concerns regarding the use of the edge-to-edge MV repair are lack of an annuloplasty ring in the majority of cases, and the risk of functional mitral stenosis. In patients with preserved annular anatomy and lack of dilatation (end-systolic diameter 34 mm), the 5-year freedom from recurrent moderate or greater MR and reoperation exceeds 90% [35, 36, 37]. The absence of a prosthetic ring may also attenuate the risk for infective endocarditis. In regards to functional mitral stenosis, stress echocardiography has shown similar transmitral pressure gradients, peak exercise oxygen uptake, and pulmonary pressures between carefully selected patients undergoing MV edge-to-edge repair and conventional MV annuloplasty operations [38, 39]. Indeed, in the present study there was no reported functional mitral stenosis at follow-up.

Reported demographics from the STS of HCM patients who undergo septal myectomy and MV repair includes a median age of 58 years, 48% female, 67% New York Heart Association functional class III/IV symptoms, and a mean LV ejection fraction of 67% [33]. The current cohort of pooled patients appears representative of this population. In the STS database of 500 concomitant septal myectomy and MV repair operations, operative mortality was 2%, 5% required a permanent pacemaker, and 0.6% developed a ventricular septal [33]. In 67 patients with HCM and intrinsic MV disease at the Cleveland Clinic, operative mortality was 3%, freedom from moderate-to-severe recurrent MR at 1-year was 90%, and 1-year and 5-year survival were 91% and 81%, respectively [32]. Of note only 16% of patients received an annuloplasty ring as part of the MV repair, and 13% were treated with an edge-to-edge stitch in that report. Placed within the context of these data, the current study supports the edge-to-edge MV repair as a viable treatment option for carefully selected HCM patients undergoing septal myectomy and confers outcomes similar to historical and conventional series.

There are several limitations to consider when interpreting the current data. Firstly, 5 of the 6 included studies were retrospective in nature which confers an inherent selection bias. Additionally, the data are essentially observational due to the lack of a comparative control group. Secondly, the sample size was small which decreases statistical power, and not all of the measured variables were available uniformly across the studies. This latter point is important as it represents a form of attrition bias. Thirdly, a substantial number of patients had abnormalities of the MV apparatus in the form of anterior MV leaflet elongation or papillary muscle pathology, or underwent other surgical procedures in addition to septal myectomy and edge-to-edge MV repair. Furthermore, the operations were performed using transaortic access or through an atriotomy, with no specific details regarding outcomes based on the approach. The heterogeneity of the population in terms of pathology, as well as in the additional cardiac procedures performed in a small subgroup of patients, impacts the operative risk and is a form of performance bias. Finally, the follow-up was limited to approximately 3 years. Given the relatively young age of the population and typical clinical course of HCM, these results cannot be interpreted as representative of long-term outcomes.

In conclusion, combined septal myectomy and edge-to-edge MV repair is a safe and viable treatment strategy in the surgical management of HCM. The current data are best interpreted as supporting the effectiveness of this approach in carefully selected patients, with larger and longer-term studies warranted to assess clinical benefit and durability.

CGM, EE, and FN—study design; CGM, RF—data analysis; CGM, EE, RF—methodological assessment and results; CGM, EE, RF, FN—manuscript writing. All authors read, edited, and approved the final version of the manuscript.

Not applicable.

Not applicable.

This research received no external funding.

The authors declare no conflict of interest. Christos G. Mihos and Francesco Nappi are serving as the Guest editors of this journal. We declare that Christos G. Mihos and Francesco Nappi had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Peter A. McCullough.