Discussion
Our case report deals with an obscure anatomic variation, probably a congenital abnormality, of the mitral annulus in which there is still little literature. For the first time, in a study of 900 hearts from adult autopsies, Hutchins et al. in 1986 reported a strong association between the mitral annular disjunction and the presence of MVP (92% of typical floppy mitral valves showed MAD); they also found out that it could be detected in approximately 6% of patients without MVP [1]. This feature was also clinically confirmed by Konda et al. in a study performed in order to investigate frequencies and characteristics of mitral annular disjunction in patients referred to an echocardiography laboratory. They even found a significantly larger percentage of cases (12%) with mitral annular disjunction but no floppy mitral valve [2]. They also reported meaningfully larger distance of the mitral annular disjunction in patients affected by MVP than in patients without it and was not founded any relationship between mitral annular disjunction and the degree of mitral regurgitation (MR).
An increased frequency of premature ventricular beats, chest pain and non-sustained ventricular tachycardia was firstly demonstrated by Carmo et al. in patients with MAD in the setting of MVP [4]; this was subsequently proved by the examination of 116 patients with MAD by Dejgaard et al. This is the first large clinical trial on patients with MAD where the authors examined patients with MAD clinically and by echocardiography and cardiac magnetic resonance (CMR), in order to describe the clinical presentation, MAD morphology, association with MVP and ventricular arrhythmias. The most important finding was, however, the high occurrence of ventricular arrhythmias in patients with MAD, independently of concomitant MVP, suggesting the existence of a novel clinical syndrome: MAD arrhythmic syndrome. They also identified young age, lower ejection fraction and papillary muscle fibrosis as markers for severe arrhythmic events. Interestingly, MAD patients with MVP were less likely to have experienced severe arrhythmic events, unlike other papers [3].
The association between MAD and arrhythmic MVP was provided by Basso and Perazzolo Marra. They postulated a cascade of events caused by MAD and leading to electrical instability and also hypothesized papillary muscle, inferobasal wall stretch and fibrosis as arrhythmogenic areas in MVP. The reason of this postulation was the observation of premature ventricular beats originating from these LV sites [5] [6]. Posterior systolic curling caused by MAD might create a mechanical stretch of the inferobasal wall and papillary muscle (PM), leading to myocardial hypertrophy and scarring [7]. The association between LV fibrosis and ventricular arrhythmias in MAD was than confirmed by Dejgaard et al. [3]. MAD itself, even independently from MVP, can therefore account for mechanical stretch of the myocardium and arrhythmogenesis [8].
The main instruments to detect MAD are echocardiography and cardiac magnetic resonance. Absence of myocardium during systole between the posterior mitral valve annulus and adjacent basal segments of the ventricular wall is representative of MAD. On echocardiography, this is most commonly seen in the parasternal long-axis view [9].
Studies focused on MAD, using CMR, confirmed that in patients with late gadolinium enhancement (LGE), presence of LV fibrosis at level of papillary muscle was more frequent in patient with MAD and, according to other studies, showed that patients with MAD have the tendency to be younger and with lower ejection fraction (LVEF), irrespectively of MR severity [10].
A review of several studies showed up that the occurrence of ventricular arrhythmias was higher with a greater extent of MAD distance and circumferential area, highlighting the link between electrical instability and extent of MAD [9]. A MAD with disjunction of >8.5 mm was revealed to be prognostic of an increased risk of ventricular arrhythmias [4].
Recently, since MAD has been suggested as a possible cause of ventricular arrhythmias and sudden cardiac death, Scheirlynck et al. carried out a study to explore the presence of soluble suppression of tumorigenicity-2 (sST2) and transforming growth factor-β1 (TGFβ1) as stretch-related and fibrosis-related biomarkers in MAD patients. They found that circulating sST2 levels were higher in patients with MAD and ventricular arrhythmias, compared with arrhythmia-free patients, while TGFβ1 levels did not differ. Interestingly, they hypothesized that the combination of sST2, LVEF and LGE assessment might detect high-risk individuals [11].