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Mitral valve prolapse (MVP) associated with severe mitral regurgitation is a debilitating disease with no pharmacological therapies available. MicroRNAs (miRNA) represent an emerging class of circulating biomarkers that have never been evaluated in MVP human plasma. Our aim was to identify a possible miRNA signature that is able to discriminate MVP patients from healthy subjects (CTRL) and to shed light on the putative altered molecular pathways in MVP. We evaluated a plasma miRNA profile using Human MicroRNA Card A followed by real-time PCR validations. In addition, to assess the discriminative power of selected miRNAs, we implemented a machine learning analysis. MiRNA profiling and validations revealed that miR-140-3p, 150-5p, 210-3p, 451a, and 487a-3p were significantly upregulated in MVP, while miR-223-3p, 323a-3p, 340-5p, and 361-5p were significantly downregulated in MVP compared to CTRL ( p ≤ 0.01). Functional analysis identified several biological processes possible linked to MVP. In addition, machine learning analysis correctly classified MVP patients from CTRL with high accuracy (0.93) and an area under the receiving operator characteristic curve (AUC) of 0.97. To the best of our knowledge, this is the first study performed on human plasma, showing a strong association between miRNAs and MVP. Thus, a circulating molecular signature could be used as a first-line, fast, and cheap screening tool for MVP identification.

Objectives: T1 mapping (T1-map) and cardiac magnetic resonance feature tracking (CMR-FT) techniques have been introduced for the early detection of interstitial myocardial fibrosis and deformation abnormalities. We sought to demonstrate that T1-map and CMR-FT may identify the presence of subclinical myocardial structural changes in patients with mitral valve prolapse (MVP)., Methods: Consecutive MVP patients with moderate-to-severe mitral regurgitation and comparative matched healthy subjects were prospectively enrolled and underwent CMR-FT analysis to calculate 2D global and segmental circumferential (CS) and radial strain (RS) and T1-map to determine global and segmental native T1 (nT1) values., Results: Seventy-three MVP patients (mean age, 57 ± 13 years old; male, 76%; regurgitant volume, 57 ± 21 mL) and 42 matched control subjects (mean age, 56 ± 18 years; male, 74%) were included. MVP patients showed a lower global CS (- 16.3 ± 3.4% vs. - 17.8 ± 1.9%, p = 0.020) and longer global nT1 (1124.9 ± 97.7 ms vs. 1007.4 ± 26.1 ms, p < 0.001) as compared to controls. Moreover, MVP patients showed lower RS and CS in basal (21.6 ± 12.3% vs. 27.6 ± 8.9%, p = 0.008, and - 13.0 ± 6.7% vs. - 14.9 ± 4.1%, p = 0.013) and mid-inferolateral (20.6 ± 10.7% vs. 28.4 ± 8.7%, p < 0.001, and - 12.8 ± 6.3% vs. - 16.5 ± 4.0%, p < 0.001) walls as compared to other myocardial segments. Similarly, MVP patients showed longer nT1 values in basal (1080 ± 68 ms vs. 1043 ± 43 ms, p < 0.001) and mid-inferolateral (1080 ± 77 ms vs. 1034 ± 37 ms, p < 0.001) walls as compared to other myocardial segments. Of note, nT1 values were significantly correlated with CS (r, 0.36; p < 0.001) and RS (r, 0.37; p < 0.001) but not with regurgitant volume., Conclusions: T1-map and CMR-FT identify subclinical left ventricle tissue changes in patients with MVP. Further studies are required to correlate these subclinical tissue changes with the outcome., Key Points: • T1 mapping (T1-map) and cardiac magnetic resonance feature tracking (CMR-FT) techniques have been introduced for the early detection of interstitial myocardial fibrosis and deformation abnormalities. • In MVP patients, we demonstrated a longer global nT1 with associated reduced global circumferential (CS) and radial strain (RS) as compared to control subjects. • Among MVP patients, the mid-basal left ventricle inferolateral wall showed longer nT1 with reduced CS and RS as compared to other myocardial segments. Further studies are required to correlate these subclinical tissue changes with the outcome.

Echocardiographic reduction of RV function, measured using TAPSE, is a well described phenomenon after cardiac surgery. The aim of the present study was to investigate the relation between the modality of pericardial opening (lateral versus anterior) and the postoperative right ventricular systolic function by comparing echocardiographic parameters in patients undergoing minimally invasive or traditional mitral valve repair. 34 patients with severe mitral regurgitation due to mitral valve prolapse underwent traditional (sternotomy) operation (Group A) or minimally invasive surgery with right anterolateral thoracotomy (Group B). A postoperative TAPSE fall was found in both groups. Group A experienced a significant postoperative TAPSE fall versus Group B with p < 0.0001.

A recent histological study of resected scallop-P2 in mitral valve (MV) prolapse, showed that chordae tendinae may be missing or hidden in superimposed fibrous tissue of the leaflets, contributing to their thickening. This may have relevant clinical implication because detailed analysis of MV leaflets has a central role in the evaluation of patients undergoing repair. The aim of this study was to analyze MV leaflets focusing on thickness of prolapsing segments and the presence of chordal rupture (CR). We enrolled 246 patients (age 63 ± 13 years, 72 men) with isolated P2 prolapse and also 50 age-matched patients with normal MV anatomy as control group. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were retrospectively analyzed to quantify the length and the proximal and distal thickness of both anterior (A2) and posterior (P2) MV scallops. Measurements were performed at end diastole in the standard TTE and TEE views. TTE and TEE measurements were feasible in all cases. Echocardiographically 176 patients had CR (group A), 45 had no rupture (group B), and 25 had an uncertain diagnosis (group C). All pathological groups showed thickening and elongation of involved leaflets versus normal, whereas no differences in leaflets characteristics were found among MV groups. Most patients undergoing MV repair had CR with thickening of the prolapsed segment. These findings are in agreement with recent histological studies showing superimposed fibrous tissue on MV leaflets partially including ruptured chordae. This may also explain that in cases without ruptured chordae, thickness of the leaflets is markedly increased (hidden chordae?). In conclusion, detailed analysis of MV apparatus may further improve knowledge of these patients and may influence surgical timing., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Factors correlating to mitral annulus calcification (MAC) include risk factors predisposing to atherosclerosis. In patients with mitral valve (MV) prolapse (MVP), other anatomic or mechanical factors have been supposed to facilitate MAC. The aims of this study were, in patients with MVP undergoing MV repair, (1) to describe the prevalence and characteristics of MAC, (2) to correlate MAC with clinical risk factors, coronary involvement, and aortic valve disease, and (3) to describe prevalence, site, and extension of MAC in fibroelastic deficiency (FED) versus Barlow's disease (BD) and correlate MAC to surgical outcomes (repair vs replacement). In 410 consecutive patients with MVP suitable for surgical MV repair, detailed clinical and echocardiographic data were collected to characterize MAC in BD and FED. MAC was found in 99 patients (24%). Age, female gender, coronary artery disease, and cardiovascular risk factors were correlated with MAC. MAC was equally distributed in FED and BD groups despite patients with FED being older with more cardiovascular risk factors. The most common localization of MAC was annular involvement adjacent to P2 (75%), P1 (31%), and P3 (35%). The presence of MAC affected surgical outcomes in both groups (8% patients with MAC underwent replacement after a first attempt of repair vs 3% without MAC). MAC is a common finding in patients undergoing MV repair, and several clinical characteristics correlate with MAC either in FED or BD. In conclusion, despite very high percentage of repairability, MAC influences surgical outcomes and very detailed echo evaluation is advocated., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aims: Mitral valve (MV) repair is the preferred treatment for mitral regurgitation associated with organic MV prolapse (MVP). Our goals were to describe by transthoracic real-time 3D echocardiography (RT3D TTE) the pre-operative changes in mitral annulus (MA) dynamic morphology related to MVP, compared with a normal population, and to evaluate the differential long-term effects induced by annuloplasty, using either an incomplete flexible band or a complete semi-rigid ring., Methods and Results: Forty-four patients (62 ± 11 years) with organic MVP and ejection fraction >55% were studied by RT3D TTE the day before MV repair, and 3 and 6 months after (23 patients received a complete rigid ring-CAR, 21 an incomplete flexible band-COS). An age-matched group of 20 normal subjects (57 ± 9 years) was studied as control. After initialization, the MA was tracked frame-by-frame in 3D, and several parameters computed. Differences in MVP vs. controls, vs. pre-surgery, and between rings were tested (P < 0.05). MVP showed enlarged MA resulting in greater area and height during the cardiac cycle, with reduced planarity compared with controls. Annuloplasty resulted in reduced MA area in both CAR and COS, with minimal area change, and planar shape (more evident in CAR than COS)., Conclusion: The main factor affecting MA function after annuloplasty appears to be the undersizing of the MA dimensions, and not the choice of the ring. This methodology could represent the basis for further evaluation of implanted rings, to provide the surgeon with additional information to be used in the pre-surgical planning and ring selection.

Aims: The aim of this study, undertaken in patients who underwent mitral valve (MV) repair surgery, was to evaluate the accuracy of pre-operative three-dimensional (3D) transthoracic echocardiography (TTE) in the evaluation of MV pathology in cases with simple or complex lesions., Methods and Results: Two hundred consecutive patients with severe mitral regurgitation due to degenerative MV prolapse underwent a complete 3DTTE the day before surgery. Three-dimensional TTE data were compared with MV surgical inspection. Three-dimensional echocardiography was feasible in a relatively short time (5 ± 3 min) with good (67%) and optimal (21%) imaging quality in the majority of cases. Three-dimensional TTE allowed an accurate identification (95% accuracy) of all MV lesions. Seventy-three (36.5%) patients had simple lesions at 3DTTE and 71 of them (97.2%) underwent a simple surgical procedure; 127 (63.5%) had complex lesions at 3DTTE and, in these cases, surgeons performed either simple procedures (48%) or complex procedures (47.2%) or valve replacement in 4.7% (after a first attempt for repair)., Conclusion: Three-dimensional TTE is feasible, not time-consuming, and accurate in identifying cases with simple vs. complex MV lesions.

Objectives: The aim of this study, undertaken in patients who underwent mitral valve (MV) repair surgery, was to evaluate the feasibility and accuracy of 3-dimensional (3D) transthoracic (TTE) and transesophageal (TEE) echocardiography in the evaluation of MV pathology., Background: A pre-operative assessment of MV anatomy is essential to surgical design in patients undergoing MV repair. Although 2-dimensional (2D) echocardiography provides precise information regarding MV anatomy, 3D TTE and 3D TEE could increase the understanding of MV apparatus and individual scallop identification., Methods: One-hundred-twelve consecutive patients with severe mitral regurgitation due to MV prolapse underwent a complete 2D and 3D TTE the day before surgery and a complete 2D and 3D TEE in the operating room. Echocardiographic data obtained by the different techniques were compared with surgical inspection., Results: Three-dimensional techniques were feasible in a relatively short time (3D TTE: 7 +/- 4 min; 3D TEE: 8 +/- 3 min), with good (3D TTE 55%; 3D TEE 35%) and optimal (3D TTE 21%; 3D TEE 45%) imaging quality in the majority of cases. Three-dimensional TEE allowed more accurate identification (95.6% accuracy) of all MV lesions in comparison with other techniques. Three-dimensional TTE and 2D TEE had similar accuracies (90% and 87%, respectively), whereas the accuracy of 2D TTE (77%) was significantly lower., Conclusions: Three-dimensional TTE and TEE are feasible and useful methods in identifying the location of MV prolapse. They were superior in the description of pathology in comparison with the corresponding 2D techniques and should be regarded as an important adjunct to standard 2D examinations in decisions regarding MV repair.