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Nearly 60 years after the first description by Barlow, mitral valve prolapse (MVP) still remains a diagnosis of great interest and intense controversy.
This continuing concern is driven by the high prevalence of this valvular disorder, detected in 1.2%–2.4% of the general population,1 and its not infrequent association with symptoms including atypical chest pain, exertional dyspnoea, palpitations and anxiety (MVP syndrome) and clinical findings including mid-systolic click, low blood pressure, leaner build and ECG anomalies. It is also common in cardiovascular conditions including significant mitral regurgitation (MR), infective endocarditis, cerebrovascular ischaemic events, ventricular arrhythmias (VAs) and even sudden cardiac death (SCD).2
On the other hand, strong controversy arises from the general lack of knowledge of the pathophysiological basis underlying most of these associations, especially with VAs and SCD, which might be coincidental in such a common disorder like MVP.
MVPs are not all the same
Over the last few years, however, we have learnt that MVPs are not all the same, and that the ‘arrhythmic MVP’ is a peculiar clinical entity, characterised by specific mitral valve apparatus abnormalities, such as myxomatous, redundant and prolapsing leaflets, mitral annular disjunction (MAD), replacement fibrotic changes in papillary muscles and basal myocardium. Furthermore, high electrical instability puts patients, especially young women, at risk of life-threatening VAs and SCD.
The pathophysiological link between these features is far from being elucidated, although our group recently proposed a causal relationship between the morphofunctional abnormalities of the mitral annulus (MAD and systolic curling motion), the myxomatous degeneration of the valve, the development of myocardial substrates (left ventricular (LV) hypertrophy and replacement-type fibrosis) and the genesis of malignant VAs.3 More in detail, the altered geometry and mechanics of the mitral annulus may account for a repetitive mechanical stretch to the valve and LV myocardium (including papillary muscles), progressively leading to myxomatous degeneration and arrhythmogenic myocardial scars, which characterise the arrhythmic (or malignant) MVP phenotype.
Mitral regurgitation in arrhythmic MVP
Our hypothesis arose from studies involving patients with MVP with absent or trivial MR, in order to exclude any confounding effects of LV volume overload and heart failure complications, resulting from a high degree of MR.4
On the contrary, the study reported by van Wijngaarden et al 5 in this issue of Heart, retrospectively enrolled a large population of consecutive patients with MVP and preserved LV ejection fraction, having a significant MR with indication for mitral valve surgery. Data regarding clinical assessment, basal ECG, arrhythmic profile and strain echocardiography were collected prior to surgery, in order to determine VA prevalence and complexity in these patients, and to identify the clinical, ECG and echocardiographic parameters involved in the genesis of VAs. Interestingly, similarly to that observed in patients with MVP without significant MR, among those with significant MR, symptomatic VAs were more common in female patients with larger mitral valve annulus, and were more frequently associated with ECG inferior T-wave inversion, MAD and systolic curling of the LV inferior wall. Thus, these clinical and instrumental features seem to be the key markers of risk of VA in MVP, irrespective of MR degree (figure 1).
Unfortunately, data about cardiac magnetic resonance (CMR) findings were not available, and therefore, the relationship between myocardial fibrosis and VAs in MVP could not be explored in this study.
Nevertheless, we already know from a recent study by Kitkungvan et al 6 that among patients with primary MR, those with MVP show the highest prevalence of LV fibrosis and VAs, at all degrees of MR severity. Thus, taking into consideration all these factors, these findings indicate the presence in MVP of a potential electrical instability, which is irrespective of LV remodelling due to volume overload caused by MR.
The role of myocardial strain parameters in arrhythmic MVP risk stratification
Speckle tracking echocardiography enables assessment of myocardial strain, and provides accurate information on global and regional LV deformation.
In patients with valvular heart disease, reduced LV global longitudinal strain indicates subtle impairment of LV systolic function, despite preserved LV ejection fraction.7 Likewise, in arrhythmic cardiomyopathies, increased LV mechanical dispersion reflects ventricular contraction heterogeneity, which predisposes patients to a higher risk of VAs onset.8 In the study by van Wijngaarden, both of these strain-related parameters were more frequently abnormal in patients with MVP with VAs, providing in these patients an incremental value in the risk prediction of VAs.5
These findings, though clinically relevant, do not clarify an important piece of the complex pathogenesis of arrhythmic MVP. Indeed, whether LV deformation anomalies follow or precede the myocardial tissue changes is unknown and cannot be inferred by these data. In other words, the functional abnormalities might be the expression of either the underlying micro/macroscopic fibrosis or of the severe mechanical stress on LV myocardium by a myxomatous mitral valve, which could trigger fibrotic remodelling (and arrhythmogenesis) over time. While in the first scenario, subclinical functional abnormalities might suggest the presence of irreversible anatomical changes, in the second they might serve as an early warning of reversible ones. Their detection, nevertheless, combined with that of symptomatic VAs (but irrespective of MR severity), might guide the timing of surgical intervention in patients with arrhythmic MVP, in order to preserve myocardial function, control VAs and prevent SCD.
Effect of surgical mitral valve repair on arrhythmic burden
Complete knowledge about the role of surgical mitral valve repair or replacement in reducing the burden of VAs in patients with MVP is not still available, also due to the fact that up to now the majority of data come from small case series and case reports. Thus, future prospective studies on the effect of surgical repair on MVP electrical instability, also including CMR findings, are needed and will be of great help for a better understanding of the pathophysiological mechanism of ‘arrhythmic MVP’.
The authors thank Tommaso Fabris, MD (Department of Cardiac,Thoracic, Vascular Sciences and Public Health, University of Padua, Italy) for his help in preparing the figure, and Barbara Hildenbrand for her diligent proof-reading of the manuscript.
Contributors Drafting of the manuscript: AC. Critical revision of the manuscript for important intellectual content: BB. All authors certify that this material or similar material has not been and will not be submitted to or published in any other publications.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Provenance and peer review Commissioned; internally peer reviewed.
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