Introduction

Hypertrophic cardiomyopathy (HCM) is considered the most prevalent inherited myocardial disease and demonstrates phenotypic and genetic heterogeneity. Beyond hypertrophy, mitral valve (MV) derangement is a common finding, often culminating in systolic anterior motion (SAM) of the MV leaflets and dynamic left ventricular outflow tract (LVOT) obstruction, an important pathophysiological hallmark in HCM.¹ This promotes the development of mitral regurgitation (MR) in many patients with HCM, aggravating even more progressive symptomatology, arrhythmias, and heart failure. For those patients who are refractory to pharmacological management, septal reduction therapies including percutaneous alcohol septal ablation and surgical myectomy have proven to be highly effective in relieving obstructive symptoms and reducing the severity of MR.^2,3 In contrast to data supporting isolated septal reduction therapy, some studies highlight significant clinical improvement in patients undergoing MV repair surgery in conjunction with the myectomy itself.^4-6 From a clinical perspective, it is imperative to understand and recognize abnormalities in the MV and supporting apparatus as clinical markers that guide management strategies along with associated implications for septal reduction therapy planning. How often MV intervention procedures "should" be performed as part of septal reduction remains controversial¹ and, in practice, depends on the extent and pattern of left ventricular hypertrophy (LVH), morphology of the MV and associated apparatus, and the presence of any intrinsic MV leaflet disease.

Pathophysiology of MR in Obstructive HCM

In HCM, primary functional and structural abnormalities of the MV apparatus are recognized as a primary phenotypic expression independent of LVH. Pathologic elongation and thickening of MV is commonly observed, although the precise pathogenetic mechanism remains to be elucidated.⁷ Along with anterior displacement and abnormal insertion points of the papillary muscles and abnormal attachment of chordae tendineae, the elongated leaflets precipitate septal contact and SAM of the MV leaflets, thereby leading to LVOT obstruction and MV leaflet malcoaptation.¹ These mechanistically unique abnormalities typically result in eccentric, posteriorly directed MR. Several examples of MV abnormalities that may be seen at the time of HCM septal reduction therapy are shown in Figure 1.

Figure 1: Examples of MV Abnormalities in Patients With HCM

Septal Reduction Therapy: Surgical Myectomy Versus Alcohol Septal Ablation

To relieve outflow tract gradient in patients with obstructive HCM with increased septal thickness, septal myectomy was first introduced by Morrow in the 1960s and has been widely adopted in select, experienced referral centers throughout the world. Guidelines on HCM have identified surgical myectomy as a gold standard therapy for non-pharmacological management for obstructive HCM.⁸ In addition, percutaneous alcohol septal ablation, a less invasive procedure, may be used as an alternate option for select patients with HCM, especially those with high surgical risk.⁹ Recently, alcohol septal ablation has gained more popularity in some referral centers with extensive experience with this intervention. Data have been mixed about the incidence of adverse outcomes related to scar formation post-ablation, although two fairly recent cohorts suggest reasonable outcomes.^10,11 The decision for alcohol septal ablation, though, must take into account the important role of MV abnormalities causing or exacerbating LVOT obstruction in patients with HCM. Thus, the suitability of coronary artery anatomy as well as morphological abnormalities of the MV and supporting apparatus should be taken into consideration when septal reduction therapy is indicated. Significant MV abnormalities of the leaflets or papillary muscles may be treated by surgical intervention at the time of myectomy but are not easily addressed by alcohol septal ablation.

When Do We Need Concomitant MV Interventions?

Whether MV abnormalities are surgically intervened upon at the time of myectomy remains controversial (in the absence of primary MV disease).¹ Prior studies showed that extensive myectomy is an effective and safe treatment for most patients with obstructive HCM to eliminate LVOT obstruction as well as significant SAM-dependent MR and its associated symptoms (with surgical mortality rates of less than 1% at experienced centers).¹² Based on prior surgical series, the vast majority of cases do not require MV surgery (MV repair or replacement) if septal myectomy is adequate with no MV injury or abnormality. These are summarized in Table 1 (adapted from Weissler-Snir et al).¹³ However, in certain cases, isolated septal myectomy alone is unable to ameliorate SAM-related LVOT obstruction.¹⁴ Although a significant decrease of SAM-related MR has been observed, residual MR may occur after isolated myectomy due to inadequate resection, primary MV abnormality, or iatrogenic MV injury.¹³ Hence, concomitant MV interventions might be required to treat both obstruction and valvular abnormalities. Such MV interventions include MV replacement, MV repair, anterior MV leaflet plication, extension or retention plasty, and MV apparatus reconstruction.^6,13,15 Some referral centers in North America and Europe preferably perform MV intervention in addition to surgical myectomy in a subgroup of patients with marked LVOT obstruction and relatively mild septal hypertrophy.^16,17 This approach appears reasonable as long as a particular focus is given to individualize the MV intervention, with MV repair being the preferred technique. Figure 2 illustrates a patient with mild LVH and relief of LVOT obstruction with combined myectomy and papillary muscle reorientation surgery. Recently, there have been small studies showing the potential use of the MitraClip (Abbott; Abbott Park, IL) device to perform MV plication in patients with obstructive HCM with poor surgical candidacy.^18,19 Although the preliminary results have suggested that MitraClip might be effective to relieve LVOT obstruction, alleviate MR, and improve associated symptoms, a large, multicenter study is clearly warranted to further evaluate its generalizability and long-term outcomes.

Table 1: Surgical Myectomy Series and Rates of MV Surgery (MV Repair or Replacement)¹³

First AuthorRef (Location)	Year	N	MV Surgery (%)	MV Repair (%)	MV Replacement (%)
Mohr23 (Rochester, MN)	1989	115	5.2	0	5.2
Heric24 (Cleveland, OH; Tacoma, WA; Buffalo, NY)	1995	178	11.9	2.3	9.6
Schönbeck25 (Zurich, Switzerland)	1998	110	10.9	9.1	1.8
Kaple4 (Cleveland, OH)	2008	851	13.5	7.9	5.6
Iacovoni22 (Bergamo, Italy)	2012	124	7.2	5.6	1.6
Balaram20 (New York, NY)	2012	132	76.0	65.0	11.0
Wang26 (Beijing, China)	2013	93	20.4	9.7	10.7
Desai27 (Cleveland, OH)	2015	990	24.2	20.4	3.8
Hong2 (Rochester, MN)	2016	1,993	8.8	6.7	2.1
Ralph-Edwards[unpublished data] (Toronto, Canada)	2016	577	5.7	4.2	1.5

Figure 2: Case of a Patient With Mild Septal LVH but Severe LVOT Obstruction

Preoperative Diagnostic Approach

Multimodality cardiac imaging, such as transthoracic echocardiography (TTE), transesophageal echocardiography (TEE) and cardiac magnetic resonance (CMR), is widely utilized to enhance the characterization of the HCM phenotype.^1,7,15 These imaging techniques play an important role in characterizing valvular morphology and function, defining the severity of MR, and planning for optimal septal reduction therapy. Adequate myectomy contributes to enlarged LVOT and enhanced forward blood flow, alleviating or even eliminating significant MR. However, previous studies demonstrated that concomitant non-myectomy surgery is frequently required in some patients because isolated myectomy or alcohol septal ablation would not effectively relieve symptomatic LVOT obstruction.^6,20 Such patients have been found to have MR-causing intrinsic MV abnormalities such as degenerative MV diseases (MV prolapse and ruptured chords), restrictive abnormalities, papillary abnormalities (accessory muscle and abnormal insertion), or iatrogenic MV damage.^13,14 Some patients with significant LVOT obstruction who require additional MV intervention have significantly elongated anterior MV leaflet, bifid papillary muscle mobility, and abnormal chordal attachment despite no severe basal septal hypertrophy.¹⁷ Given the variety of mechanisms causing LVOT obstruction and MR, multimodality imaging plays an important role in characterizing the mechanism of LVOT obstruction and MV morphology because each modality brings different capabilities to the table. All patients should undergo an initial comprehensive TTE study to document LVH and other relevant cardiac morphology, including MV anatomy and function. A TEE is highly recommended for a complete preoperative evaluation for surgical myectomy, particularly when a TTE is not sufficient to delineate the mechanism of MR and define the MV abnormalities. Furthermore, a TEE may be able to detect any concurrent organic cause of obstruction (e.g., a subaortic membrane).^15,21 CMR may be used to characterize MV and papillary muscle morphology and attachment due to superior spatial resolution and is not limited by echocardiography imaging windows.⁷ Three-dimensional imaging obtained within each modality may enable more complete geometric assessment of septal hypertrophy and MV structure.¹⁵ Typically, primary MV abnormalities are found preoperatively; however, in some patients, these abnormalities were detected only intraoperatively.¹³ Thus, it is worth noting that an intraoperative TEE plays an important role in reassessing the need for possible MV intervention at the time of surgery. In addition, TEE can provide confirmation of adequate septal resection and resolution of LVOT obstruction and MR during the procedure.²²

Conclusion

In patients with obstructive HCM who are refractory to pharmacological treatment, subsequent management includes septal reduction therapy and/or MV intervention. Diagnostic evaluation requires an understanding of the contribution of potential MV abnormalities to pathophysiology at the patient level. In many cases, isolated surgical myectomy (or alcohol septal ablation) may be sufficient; in specific instances, concomitant MV surgical repair may be required. Novel percutaneous interventions may provide additional therapeutic options. Finally, multimodality cardiac imaging techniques facilitate a comprehensive perioperative assessment of the MV and its supporting apparatus, permitting a tailored approach that completely addresses the underlying mechanism(s) of heart failure.

References

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Keywords: Arrhythmias, Cardiac, Biomarkers, Cardiac Imaging Techniques, Diagnostic Imaging, Cardiac Surgical Procedures, Cardiomyopathy, Hypertrophic, Chordae Tendineae, Cicatrix, Coronary Vessels, Echocardiography, Echocardiography, Transesophageal, Genetic Heterogeneity, Heart Failure, Hypertrophy, Hypertrophy, Left Ventricular, Iatrogenic Disease, Imaging, Three-Dimensional, Magnetic Resonance Spectroscopy, Mitral Valve, Mitral Valve Insufficiency, Operating Tables, Papillary Muscles, Phenotype, Prolapse, Systole

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