Unveiling the distinctive features of arrhythmic mitral valve prolapse by three-dimensional left ventricular shape modelling and late-gadolinium-enhancement microstructure analysis

Background Arrhythmic mitral valve prolapse (aMVP) is associated with malignant ventricular arrhythmias (VA) despite the absence of significant mitral regurgitation (MR) or left ventricular (LV) dysfunction. Advances in cardiovascular magnetic resonance (CMR) provided opportunities to implement a-MVP characterization. However, validated imaging biomarkers for risk stratification are still missing. Purpose Given the low prevalence of aMVP in the population, cohort studies are unsuited for in-depth phenotyping. We therefore conducted a nested case-control study using CMR, including three-dimensional (3D) LV shape modelling and multi-parametric myocardial fibrosis (MF) analysis, to investigate the relative contribution of potentially relevant aMVP features. Methods In this nested case–control study, 23 aMVP patients (cases; 51±17 years, 52% male, presenting with sustained ventricular tachycardia or aborted sudden cardiac death) were age- and sex-matched to 69 MVP patients without malignant VA (naMVP, controls; 50±15 years, 49% male). Cases and controls had no or mild MR and all underwent CMR with late-gadolinium-enhancement (LGE) to quantify MF microstructure by an in-house software using 5-standard-deviation algorithm. LV geometry was assessed by 3D shape modelling using short-axis cine images. Results LV volumes and mass were comparable between groups while LVEF was slightly lower in cases than controls (57±7% vs 60±7%, P=0.049). Mitral annulus disjunction (MAD) prevalence was similar in the two groups, yet aMVP exhibited greater posterior mitral leaflet systolic displacement (8.58 mm vs 7.1 mm, P=0.01) and MAD length (8.5± 3.6mm vs 5.6±3.4 mm, P=0.039). MF was more often detected in aMVP than naMVP (57% vs 32%, p=0.035) with larger fibrosis burden (4.1±2.7% vs 2.4±2.4% of LV mass, P=0.015) and dense MF core volume (median 54.9 ml vs. 18.8 ml, P=0.014). MF microstructure analysis, including mean entropy and volume of critical VT isthmus sites, did not significantly differ between groups. However, 3D LV shape analysis revealed consistent abnormalities in LV geometry in aMVP, including increased LV sphericity and regional remodelling not captured by conventional imaging biomarkers, as larger end-diastolic (ED) apical LV diameters, wider epicardial end-systolic (ES) diameters both at basal and mid levels, and greater ED and ES wall thickness at basal segments. Conclusion aMVP is characterized by a distinct phenotype with more advanced mitral apparatus abnormalities, LV geometric remodelling, and greater MF burden. However, microstructure MF analysis did not reveal substantial differences between aMVP and naMVP, potentially suggesting that MF likely reflects geometrical and functional alternations related to MVP mechanics rather than representing a primary arrhythmogenic substrate. Our study. using advanced CMR phenotyping and case–control design, extends prior observations and supports improved arrhythmic risk stratification in MVP.Figure 1Figure 2