Abnormal Mechanics Relate to Myocardial Fibrosis and Ventricular Arrhythmias in Patients With Mitral Valve Prolapse

Abstract

Background: The relation between ventricular arrhythmia and fibrosis in mitral valve prolapse (MVP) is reported, but underlying valve-induced mechanisms remain unknown. We evaluated the association between abnormal MVP-related mechanics and myocardial fibrosis, and their association with arrhythmia. Methods: We studied 113 patients with MVP with both echocardiogram and gadolinium cardiac magnetic resonance imaging for myocardial fibrosis. Two-dimensional and speckle-tracking echocardiography evaluated mitral regurgitation, superior leaflet and papillary muscle displacement with associated exaggerated basal myocardial systolic curling, and myocardial longitudinal strain. Follow-up assessed arrhythmic events (nonsustained or sustained ventricular tachycardia or ventricular fibrillation). Results: Myocardial fibrosis was observed in 43 patients with MVP, predominantly in the basal-midventricular inferior-lateral wall and papillary muscles. Patients with MVP with fibrosis had greater mitral regurgitation, prolapse, and superior papillary muscle displacement with basal curling and more impaired inferior-posterior basal strain than those without fibrosis ( P <0.001). An abnormal strain pattern with distinct peaks pre–end-systole and post–end-systole in inferior-lateral wall was frequent in patients with fibrosis (81 versus 26%, P <0.001) but absent in patients without MVP with basal inferior-lateral wall fibrosis (n=20). During median follow-up of 1008 days, 36 of 87 patients with MVP with >6-month follow-up developed ventricular arrhythmias associated (univariable) with fibrosis, greater prolapse, mitral annular disjunction, and double-peak strain. In multivariable analysis, double-peak strain showed incremental risk of arrhythmia over fibrosis. Conclusions: Basal inferior-posterior myocardial fibrosis in MVP is associated with abnormal MVP-related myocardial mechanics, which are potentially associated with ventricular arrhythmia. These associations suggest pathophysiological links between MVP-related mechanical abnormalities and myocardial fibrosis, which also may relate to ventricular arrhythmia and offer potential imaging markers of increased arrhythmic risk.

Challenges and Opportunities in Valvular Heart Disease: From Molecular Mechanisms to the Community

“…23 Molecular histopathology further differentiates diffuse myxomatous disease from more localized disruption in fibroelastic deficiency, while imaging valve strain can innovatively link basic and mechanical changes. 24 In future, interactions of valves with annular and ventricular structures provide opportunities to study the intersection of biomechanics and molecular changes through understanding how flattening the mitral annular saddle can augment leaflet stresses and worsen mitral valve prolapse 25 ; how prolapse-induced forces can generate localized, proarrhythmic ventricular fibrosis 26 ; and how local and global remodeling of the ischemic or myopathic ventricle can trigger intrinsic valve changes.…”

Utilization of Engineering Advances for Detailed Biomechanical Characterization of the Mitral–Ventricular Relationship to Optimize Repair Strategies: A Comprehensive Review

“…Direct evidence of increased forces on the papillary muscle due to single or bileaflet MVP was demonstrated recently using the elaborate ex vivo simulator at the Woo laboratory at Stanford and a novel system to adjust the primary chordae tendineae length without manipulating any other elements of the MV and subvalvular structures (see Figure 13) [44]. Furthermore, utilizing advanced mechanical analysis based on an echocardiography-derived LV strain, it was found that altered longitudinal strain is seen in the basal inferolateral myocardium, situated between the mitral annulus and papillary muscles in patients with MVP compared with healthy controls [155]. In addition, studies have observed a decrease in papillary muscle systolic shortening associated with MVP, which may reflect increases in the tissue stiffness due to either PM fibrosis or opposing stretching forces as a results of the increase in tension from the prolapsing valve [156].…”

“…Computationally, Zhang and colleagues [2019] also demonstrated that this device induces abnormal strains in the ventricular wall. Taking into account the current evidence for abnormal mechanics in MVP due to increased traction forces that are independently associated with the presence of localized fibrosis and the occurrence of life-threatening ventricular arrhythmias [155], this may have larger implications for long-term outcomes; however, it remains a topic of much needed ongoing research efforts.…”

An iPSC-derived bio-inspired scaffold modelling the structure and the effects of extracellular matrix in cardiac fibrosis

“…Since adult cardiac tissue lacks endogenous stem cells with in vivo regenerative potential, the loss of terminally differentiated contractile cells cannot be replenished [ 10, 11,12 ] . Moreover, during the late stage of fibrosis, myofibroblasts undergo apoptosis, the ECM stiffens, and the abundant matrix infiltrates between the remaining functional cardiomyocytes (CMs), thus leading to arrhythmic events which compromise the heart function [ 7,13 ] . Different strategies have been devised to modulate cardiac fibroblasts activation and reduce the symptoms of cardiac fibrosis with contrasting results.…”