A new index for the diagnosis of outflow obstruction in hypertrophic cardiomyopathy: is it accurate? and if so, is it useful?

This editorial refers to ‘Spatial relationship between mitral valve and ventricular septum assessed by resting echocardiography to diagnose left ventricular outflow tract obstruction in hypertrophic cardiomyopathy’, by N. Verheyen et al., https://doi.org/10.1093/ehjci/jead036. In patients with hypertrophic cardiomyopathy (HCM), left ventricular (LV) outflow obstruction is the most common cause of heart failure symptoms and unfavourable outcome.1,2 Multiple mechanisms are responsible for outflow obstruction, including septal hypertrophy, impact of early systolic flow on the posterior surface of elongated and anteriorly displaced mitral valve (MV) leaflets, anomalous papillary muscles insertion directly into the anterior mitral leaflet, and the traction exerted on the anterior leaflet by fibrotic secondary chordae.3–5 Because of the extreme heterogeneity of HCM, these mechanisms play variable roles in producing LV outflow obstruction in individual patients at rest or during exercise. Therefore, provocative physiologic manoeuvres such as Valsalva or stress exercise are routinely performed in patients with HCM during echocardiographic examination to assess more precisely presence and severity of the subaortic gradient.1,2 In this issue of the European Heart Journal—Cardiovascular Imaging, Verheyen et al.6 report the results of their echocardiographic investigation of the spatial relation between MV leaflets and ventricular septum in a consecutive HCM cohort including 74 patients with non-obstructive HCM and 68 with LV outflow obstruction (defined as maximal peak gradient ≥30 mmHg) either at rest or with provocative manoeuvres; 59 (42%) of the study patients had previously undergone septal myectomy or alcohol septal ablation. The authors have focused their attention on the distance between mitral leaflet tip and interventricular septum (‘TIS’ in the paper) measured from the apical three-chamber view at end-systole. The results of the investigation are of interest. A TIS ≤ 9 mm identified resting or provocable LV outflow gradient with 92% positive predictive value, while a TIS >14 mm excluded an outflow gradient with 95% negative predictive value. These TIS cut-off values also identified a provocable outflow gradient in the absence of resting obstruction with 86% positive predictive value and excluded a provocable gradient with 96% negative predictive value. The selection of the TIS index by the authors is supported by extensive literature on the role played in LV outflow obstruction by the MV leaflet tip. In most patients with obstructive HCM, one mitral leaflet (usually the anterior) is abnormally elongated and by extending past the point of MV coaptation protrudes into the LV outflow tract.4,7 This distal portion of the leaflet, generally described as residual leaflet, is moved anteriorly and superiorly by the early systolic flow and triggers the development of outflow obstruction.4,7 Leaflet elongation is likely due to progressive adaptation of the MV apparatus to LV hypertrophy and altered ventricular geometry, which are the hallmarks of HCM. In a recent study, however, an anomalous muscular band interposed between anterior mitral leaflet and aorta was documented at the time of septal myectomy in the great majority of a consecutive cohort of young HCM patients with outflow obstruction, while it was extremely uncommon in older patients.8 Persistence after birth of this muscular band, which in normal subject is converted into mitral–aortic fibrous continuity during foetal development, produces a pseudo-elongated leaflet that extends past the point of MV coaptation and, by protruding into the LV outflow tract, may favour development of outflow obstruction at a young age.8 On the basis of the above considerations and the results of the study by Verheyen et al., this new TIS echocardiographic index relies on sound pathophysiological foundations and appears to have a high predictive value for the diagnosis of LV outflow obstruction either at rest or with provocation. So, where do we go from here? What does the TIS index add to the clinical armamentarium we already possess for the identification of a subaortic gradient in patients with HCM? It should be underlined that the diagnosis of LV outflow obstruction does not have the same clinical weight and implications in all HCM patients. In asymptomatic patients, identification of a subaortic gradient at rest or with provocation has prognostic implications and justifies suggesting treatment with a beta-blocking agent in the absence of contraindications.1,2 In such patients, the TIS index may prove useful to support or confirm the results of the standard echocardiographic evaluation with regard to LV outflow obstruction, particularly in non-referral HCM centres with limited experience with assessment of the maximal LV outflow gradient. In patients with important heart failure symptoms and reduced quality of life who may be eligible for septal myectomy or alcohol septal ablation, it is of crucial importance to determine with the highest possible accuracy whether symptoms are secondary to LV outflow obstruction.1,2 Therefore, in such patients, stress (exercise) echocardiography should be performed independently of the results of Valsalva or other similar physiologic manoeuvres, including the TIS index.1,2 Certain technical limitations of the TIS index should be mentioned. When the distance between the tip of the residual MV leaflet and ventricular septum fell within the values selected by the authors (within 9 mm or above 14 mm), TIS had a high predictive value for the diagnosis of LV outflow obstruction. However, when the TIS index fell in between these two numerical limits, a large grey area of uncertainty remained for the identification or exclusion of LV outflow obstruction (about 30% of the study cohort). This limitation reduces substantially the index accuracy, which is derived from sensitivity and specificity. Also, in patients with an echocardiographic window of scarce technical quality, the residual leaflet is difficult to visualize, or its true length may be difficult to determine. Therefore, the TIS index provides information only in selected patients. One more point needs to be commented upon. In this initial investigation, about 40% of the study patients had previously undergone invasive treatment for LV outflow obstruction. Such patients should be excluded from future investigations of the TIS index, because both septal myectomy and alcohol septal ablation alter the original septal contractility and spatial relation between MV leaflets and ventricular septum.1,2 Alternatively, should patients with previous septal reduction therapy be included in future investigations, data in these patients would have to be analysed separately. In conclusion, this study reports the potential of a novel echocardiographic index for the identification of LV outflow obstruction in a cohort of patients with HCM. In the field of research, new ideas are always welcome, and these preliminary results are encouraging. However, these findings should be validated in larger studies, and the possible future role of this index in the day-to-day clinical context would have to be determined. None declared. No new data were generated or analysed for the purpose of writing this manuscript.