Wnt Signaling Inhibition Prevents Postnatal Inflammation and Disease Progression in Mouse Congenital Myxomatous Valve Disease.

BACKGROUND: Myxomatous valve disease (MVD) is the most common cause of mitral regurgitation, leading to impaired cardiac function and heart failure. MVD in a mouse model of Marfan syndrome includes valve leaflet thickening and progressive valve degeneration. However, the underlying mechanisms by which the disease progresses remain undefined. METHODS: Mice with Fibrillin 1 gene variant Fbn1C1039G/+ recapitulate histopathologic features of Marfan syndrome, and Wnt (Wingless-related integration site) signaling activity was detected in TCF/Lef-lacZ (T-cell factor/lymphoid enhancer factor-ß-galactosidase) reporter mice. Single-cell RNA sequencing was performed from mitral valves of wild-type and Fbn1C1039G/+ mice at 1 month of age. Inhibition of Wnt signaling was achieved by conditional induction of the secreted Wnt inhibitor Dkk1 (Dickkopf-1) expression in periostin-expressing valve interstitial cells of Periostin-Cre; tetO-Dkk1; R26rtTA; TCF/Lef-lacZ; Fbn1C1039G/+ mice. Dietary doxycycline was administered for 1 month beginning with MVD initiation (1-month-old) or MVD progression (2-month-old). Histological evaluation and immunofluorescence for ECM (extracellular matrix) and immune cells were performed. RESULTS: Wnt signaling is activated early in mitral valve disease progression, before immune cell infiltration in Fbn1C1039G/+ mice. Single-cell transcriptomics revealed similar mitral valve cell heterogeneity between wild-type and Fbn1C1039G/+ mice at 1 month of age. Wnt pathway genes were predominantly expressed in valve interstitial cells and valve endothelial cells of Fbn1C1039G/+ mice. Inhibition of Wnt signaling in Fbn1C1039G/+ mice at 1 month of age prevented the initiation of MVD as indicated by improved ECM remodeling and reduced valve leaflet thickness with decreased infiltrating macrophages. However, later, Wnt inhibition starting at 2 months did not prevent the progression of MVD. CONCLUSIONS: Wnt signaling is involved in the initiation of mitral valve abnormalities and inflammation but is not responsible for later-stage valve disease progression once it has been initiated. Thus, Wnt signaling contributes to MVD progression in a time-dependent manner and provides a promising therapeutic target for the early treatment of congenital MVD in Marfan syndrome.

Fluid-structure interaction and structural simulation of high acceleration effects on surgical repaired human mitral valve biomechanics.

Mitral valve dynamics depend on force stability in the mitral leaflets, the mitral annulus, the chordae tendineae, and the papillary muscles. In chordal rupture conditions, the proper function of the valve disrupts, causing mitral regurgitation, the most prevalent valvular disease. In this study, Structural and FSI frameworks were employed to study valve dynamics in healthy, pathologic, and repaired states. Anisotropic, non-linear, hyper-elastic material properties applied to tissues of the valve while the first-order Ogden model reflected the best compatibility with the empirical data. Hemodynamic blood pressure of the cardiovascular system is applied on the leaflets as uniform loads varying by time, and exposure to high acceleration loads imposed on models. Immersed boundary method used for simulation of fluid in a cardiac cycle. In comparison between healthy and pathologic models, stress values and chordal tensions are increased, by nearly threefold and twofold, respectively. Stress concentration on leaflets is reduced by 75% after performing a successful surgical repair on the pathological model. Crash acceleration loads led to more significant stress and chordae tension on models, by 27% and 23%, respectively. It is concluded that a more sophisticated model could lead to a better understanding of human heart valve biomechanics in various conditions. If a preoperative plan is developed based on these modeling methods, the requirement for multiple successive repairs would be eliminated, operative times are shortened, and patient outcomes are improved.

Cardiac reverse remodeling in primary mitral regurgitation: mitral valve replacement vs. mitral valve repair.

BACKGROUND: When feasible, guidelines recommend mitral valve repair (MVr) over mitral valve replacement (MVR) to treat primary mitral regurgitation (MR), based upon historic outcome studies and transthoracic echocardiography (TTE) reverse remodeling studies. Cardiovascular magnetic resonance (CMR) offers reference standard biventricular assessment with superior MR quantification compared to TTE. Using serial CMR in primary MR patients, we aimed to investigate cardiac reverse remodeling and residual MR post-MVr vs MVR with chordal preservation. METHODS: 83 patients with ≥ moderate-severe MR on TTE were prospectively recruited. 6-min walk tests (6MWT) and CMR imaging including cine imaging, aortic/pulmonary through-plane phase contrast imaging, T1 maps and late-gadolinium-enhanced (LGE) imaging were performed at baseline and 6 months after mitral surgery or watchful waiting (control group). RESULTS: 72 patients completed follow-up (Controls = 20, MVr = 30 and MVR = 22). Surgical groups demonstrated comparable baseline cardiac indices and co-morbidities. At 6-months, MVr and MVR groups demonstrated comparable improvements in 6MWT distances (+ 57 ± 54 m vs + 64 ± 76 m respectively, p = 1), reduced indexed left ventricular end-diastolic volumes (LVEDVi; - 29 ± 21 ml/m2 vs - 37 ± 22 ml/m2 respectively, p = 0.584) and left atrial volumes (- 23 ± 30 ml/m2 and - 39 ± 26 ml/m2 respectively, p = 0.545). At 6-months, compared with controls, right ventricular ejection fraction was poorer post-MVr (47 ± 6.1% vs 53 ± 8.0% respectively, p = 0.01) compared to post-MVR (50 ± 5.7% vs 53 ± 8.0% respectively, p = 0.698). MVR resulted in lower residual MR-regurgitant fraction (RF) than MVr (12 ± 8.0% vs 21 ± 11% respectively, p = 0.022). Baseline and follow-up indices of diffuse and focal myocardial fibrosis (Native T1 relaxation times, extra-cellular volume and quantified LGE respectively) were comparable between groups. Stepwise multiple linear regression of indexed variables in the surgical groups demonstrated baseline indexed mitral regurgitant volume as the sole multivariate predictor of left ventricular (LV) end-diastolic reverse remodelling, baseline LVEDVi as the most significant independent multivariate predictor of follow-up LVEDVi, baseline indexed LV end-systolic volume as the sole multivariate predictor of follow-up LV ejection fraction and undergoing MVR (vs MVr) as the most significant (p < 0.001) baseline multivariate predictor of lower residual MR. CONCLUSION: In primary MR, MVR with chordal preservation may offer comparable cardiac reverse remodeling and functional benefits at 6-months when compared to MVr. Larger, multicenter CMR studies are required, which if the findings are confirmed could impact future surgical practice.

Image-based ring size prediction for mitral valve repair.

OBJECTIVES: Annuloplasty rings are routinely used in mitral valve repair (MVr). However, accurate annuloplasty ring size selection is essential to obtain a favourable outcome. Moreover, ring sizing can be challenging in some patients and is highly influenced by surgeons' experience. This study investigated the utility of three-dimensional mitral valve (3D-MV) reconstruction models to predict annuloplasty ring size for MVr. METHODS: A total of 150 patients undergoing minimally invasive MVr with annuloplasty ring due to Carpentier type II pathology and who were discharged with none/trace residual mitral regurgitation were included. 3D-MV reconstruction models were created with a semi-automated software package (4D MV Analysis) to quantitate mitral valve geometry. To predict the ring size, univariable and multivariable linear regression analyses were performed. RESULTS: Between 3D-MV reconstruction values and implanted ring sizes, the highest correlation coefficients were provided by commissural width (CW) (0.839; P < 0.001), intertrigonal distance (ITD) (0.796; P < 0.001), annulus area (0.782; P < 0.001), anterior mitral leaflet area (0.767; P < 0.001), anterior-posterior diameter (0.679; P < 0.001) and anterior mitral leaflet length (0.515; P < 0.001). In multivariable regression analysis, only CW and ITD were found to be independent predictors of annuloplasty ring size (R2 = 0.743; P < 0.001). The highest level of agreement was achieved with CW and ITD, and 76.6% of patients received a ring with no >1 ring size difference from the predicted ring sizes. CONCLUSIONS: 3D-MV reconstruction models can support surgeons in the decision-making process for annuloplasty ring sizing. The present study may be a first step towards accurate annuloplasty ring size prediction using multimodal machine learning decision support.

Histopathological evaluation of chronic rheumatic mitral valve stenosis: the association with clinical presentation, pathogenesis, and management at a National Cardiac Institute, Tanzania.

AIMS: The histopathology of mitral valve (MV) tissues have been reported in necropsy and retrospective studies. We prospectively studied the histopathological changes in rheumatic mitral stenosis using advanced techniques and corroborated these with clinical presentation, pathogenesis, and management. METHODS: From January 2020 to February 2021, surgically excised rheumatic stenotic MV from 54 Tanzanian patients were studied. These were examined using hematoxylin-eosin, von Kossa staining, and immunohistochemistry. RESULTS: The median (range) age of patients was 39 (14-57) years with 34 (63%) females. Secondary prophylaxis was given to 7 (13%) patients and 2 (3.7%) had evidence of rheumatic fever (RF). With hematoxylin-eosin, 37 (68.5%) specimens showed fibrinoid degeneration (FD), 44 (81.5%) leucocytic infiltrates, 6 (11.1%) Aschoff nodules, 30 (55.6%) calcification, and 39 (72.2%) fibrosis. Thirty-five (64.8%) specimens were positive to von Kossa. The proportion of specimens positive for CD3, CD20, CD68, and CD8 were 46 (85.2%), 35 (64.8%), 39 (72.2%), and 8 (14.8%) respectively. Valvular calcium was high among older patients, males and with a higher trans-MV gradient. The degree of inflammatory cellular infiltration was associated with valvular calcification, FD with ARF, leucocytic infiltrates with disease duration of <10 years, and fibrosis with the absence of atrial fibrillation. C-reactive protein and anti-streptolysin titres were high in CD20 and CD8 staining cells. CONCLUSION: This study confirms that high MV calcium are found in patients who are old, male, and with severe mitral stenosis. The association between clinical parameters with histopathological-immunohistochemical studies observed in our study provides new insight to disease presentation. We found a low rate of secondary prophylaxis and two patients with ARF. Our findings are comparable with those from other countries suggesting similar pathogenesis and thus intervention modalities. This is the first study on mitral valve histopathology to be reported from Africa.

Accessory left atrial cords: A case report and literature review.

INTRODUCTION: Accessory left atrial cords are fibroelastic structures found in the left atrium. Left atrial cords may be associated with mitral valve disease, atrial fibrillation, stroke, and other congenital left-side anomalies. METHODS: We presented the case of a man with severe Mitral Regurgitation and two accessories left atrial cords attached to P2 scallop by a single tendon and performed a literature review using PUBMED/MEDLINE, Web of Science, and EMBASE databases on December 4, 2021. RESULTS: According to our review, accessory left atrial cords were found more frequently in women (36 patients, 62%), more frequently attached to the mitral valve (66% of reports) and mitral regurgitation was the most frequently reported pattern of mitral valve disease (64.2%). No other cases of double left atrial cords attached to P2 segment were found. CONCLUSION: Accessory left atrial chords may be related to mitral valve disease and other left-side congenital abnormalities. These structures were found more frequently in females and A2 insertion was the most frequently observed pattern in the review.

Morphologic Findings in Native Mitral Valves Replaced for Isolated Acute Infective Endocarditis.

Described here are some clinical and morphological observations in 37 adults having mitral valve replacement for active infective endocarditis limited to the mitral valve. The operatively-excised mitral valves are illustrated in 11 of the 37 patients, and photographs in them show that mitral valve repair in them would have been fruitless. Of the 37 patients, 32 (86%) survived the early operative period (30 days) and 31 (84%) were alive one year after the mitral operation. Of the 37 patients, 34 (92%) appeared to have had anatomically normal mitral valves before the infective endocarditis appeared.

Effect of early versus late onset mitral regurgitation on left ventricular remodeling in ischemic cardiomyopathy in an animal model.

BACKGROUND: Patients who survive a myocardial infarction have progressive cardiac dysfunction and ventricular remodeling. Mitral regurgitation is often diagnosed in these patients, and is a risk factor that portends poor prognosis. Whether such postinfarction mitral regurgitation magnifies adverse left ventricular remodeling is unclear, which was studied in an animal model. METHODS: Forty-one adult rats were induced with myocardial infarction using left coronary artery ligation and assigned to 3 groups: group 1, myocardial infarction only; group 2, myocardial infarction with severe mitral regurgitation introduced after 4 weeks; and group 3, myocardial infarction with severe mitral regurgitation introduced after 10 weeks. Valve regurgitation was introduced by advancing a transapical ultrasound-guided needle into the mitral valve anterior leaflet. Animals were survived to 20 weeks from the index procedure, with biweekly cardiac ultrasound, and invasive hemodynamics and histology at termination. RESULTS: At 20 weeks, end diastolic volume was largest in the groups with mitral regurgitation, compared with the group without the valve lesion (group 1, 760.9 ± 124.6 µL; group 2, 958.0 ± 115.1 µL; group 3, 968.3 ± 214.9 µL). Similarly, end systolic volume was larger in groups with regurgitation (group 1, 431.2 ± 152.6 µL; group 2, 533.2 ± 130.8 µL; group 3, 533.1 ± 177.5 µL). In the infarction-only group, left ventricular remodeling was maximal until 6 weeks and plateaued thereafter. In groups with mitral regurgitation, left ventricular remodeling was significantly elevated at the onset of regurgitation and persisted. CONCLUSIONS: Mitral regurgitation is a potent driver of adverse cardiac remodeling after a myocardial infarction, irrespective of the timing of its onset.

Multiple retrospective analysis of survival and evaluation of cardiac death predictors in a population of dogs affected by degenerative mitral valve disease in ACVIM class C treated with different therapeutic protocols.

Clinical records of dogs with spontaneous degenerative mitral valve disease (DMVD) with clinical signs related to congestive heart failure (CHF) recruited during routine clinical practice between 2001 and 2018 at the Cardiology Unit of the Veterinary Teaching Hospital (University of Milan) were included in this retrospective cohort study. Baseline echocardiographic data were evaluated. Median survival time (MST) was calculated. Data on therapeutic treatment, ISACHC (International Small Animal Cardiac Health Council) or ACVIM (American College of Veterinary Internal Medicine) classes were reviewed based on the inclusion period and type of endpoint (i.e. cardiac death or death for other causes). A univocal classification was needed, and the patients classified in ISACHC classes II, IIIa and IIIb, visited before 2009, were reallocated to ACVIM class C. The main goal of this data review was to retrospectively evaluate 259 clinical records of subjects belonging to ACVIM C class examined between 2001 to 2018 and 202 dogs examined between 2010 to 2018. In this way, in the second group, the bias of the reclassification was avoided. The MST (median survival time) of these subjects was 531 d (2001-2018) and 335.5 d (2010-2018), respectively. Univariate survival regression analysis for subjects included from 2010 to 2018 showed as significantly related to cardiac death (CD): left atrium to aorta ratio (LA/Ao) (HR 2.754, p=0.000), E wave (HR 2.961, p=0.000), E/A ratio (HR 1.372, p=0.000), end-diastolic (HR 1.007, p=0.000) (EDVI) and end-systolic (HR 1.012, p=0.026) (ESVI) volume indexes, allometric diastolic (HR 4.018, p=0.000) (LVIDdN) and systolic (HR 2.674, p=0.049) (LVIDsN) left ventricular internal diameters, age (HR 1.006, p=0.009) and pulmonary hypertension severity (HR=1.309, p=0.012) (PH). Multivariate analysis, adjusted for age, showed that the only variable that determined a statistically significant difference in MST was PH severity (HR 1.334, p=0.033). The type of therapeutic treatment within this class was not significant for the MST of the subjects.

Altered Responsiveness to TGFß and BMP and Increased CD45+ Cell Presence in Mitral Valves Are Unique Features of Ischemic Mitral Regurgitation.

[Figure: see text].

Pre-surgical Prediction of Ischemic Mitral Regurgitation Recurrence Using In Vivo Mitral Valve Leaflet Strains.

Ischemic mitral regurgitation (IMR) is a prevalent cardiac disease associated with substantial morbidity and mortality. Contemporary surgical treatments continue to have limited long-term success, in part due to the complex and multi-factorial nature of IMR. There is thus a need to better understand IMR etiology to guide optimal patient specific treatments. Herein, we applied our finite element-based shape-matching technique to non-invasively estimate peak systolic leaflet strains in human mitral valves (MVs) from in-vivo 3D echocardiographic images taken immediately prior to and post-annuloplasty repair. From a total of 21 MVs, we found statistically significant differences in pre-surgical MV size, shape, and deformation patterns between the with and without IMR recurrence patient groups at 6 months post-surgery. Recurrent MVs had significantly less compressive circumferential strains in the anterior commissure region compared to the recurrent MVs (p = 0.0223) and were significantly larger. A logistic regression analysis revealed that average pre-surgical circumferential leaflet strain in the Carpentier A1 region independently predicted 6-month recurrence of IMR (optimal cutoff value - 18%, p = 0.0362). Collectively, these results suggest greater disease progression in the recurrent group and underscore the highly patient-specific nature of IMR. Importantly, the ability to identify such factors pre-surgically could be used to guide optimal treatment methods to reduce post-surgical IMR recurrence.

THAP11 down-regulation may contribute to cardio-protective effects of sevoflurane anesthesia: Evidence from clinical and molecular evidence.

This study aimed to explore the potential target of the cardio-protective effect induced by sevoflurane anesthesia based on evidence from clinical samples and in vitro model. Forty patients undergoing mitral valve replacement were randomly allocated to receive sevoflurane or propofol-based anesthesia. Atrial muscle specimens were collected from all patients, of which 5 were used to perform transcriptomics analysis. The cTn-I concentration was tested before, at the end of, and 24 h after surgery. In in vitro study, the expression level of the identified target gene, i.e., THAP11, was studied in H9C2 cells treated with sevoflurane or propofol. Then, we studied cell viability using CCK-8 staining, apoptosis by using flow cytometry, and cell death by lactic acid dehydrogenase (LDH) detection in H9C2 cells exposed to oxygen glucose deprivation/reoxygenation (OGD/R) injury. THAP11 was the most significantly down-regulated gene in the transcriptomics analysis (P < 0.001), as confirmed in validation samples (P = 0.006). THAP11 mRNA levels in atrial muscle specimens were positively associated with cTn-I levels at 24-h postoperatively (determination coefficient = 0.564; P < 0.001). Sevoflurane treatment down-regulated THAP11 in H9C2 cell models, which promoted cell viability, inhibited cell apoptosis, and death in the OGD/R injury cell model. Up-regulation of THAP11 reduced the protective effect of sevoflurane treatment against OGD/R injury. Sevoflurane anesthesia down-regulates the expression of THAP11, which contributes to a cardio-protective effect. THAP11 down-regulation promotes cell viability, and inhibits cell apoptosis and death, thereby protecting again myocardial injury; it may therefore be a novel target for perioperative cardio-protection.

Association of Effective Regurgitation Orifice Area to Left Ventricular End-Diastolic Volume Ratio With Transcatheter Mitral Valve Repair Outcomes: A Secondary Analysis of the COAPT Trial.

Importance: Transcatheter mitral valve repair (TMVr) plus maximally tolerated guideline-directed medical therapy (GDMT) reduced heart failure (HF) hospitalizations (HFHs) and all-cause mortality (ACM) in symptomatic patients with HF and secondary mitral regurgitation (SMR) compared with GDMT alone in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) trial but not in a similar trial, Multicenter Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation (MITRA-FR), possibly because the degree of SMR relative to the left ventricular end-diastolic volume index (LVEDVi) was substantially lower. Objective: To explore contributions of the degree of SMR using the effective regurgitation orifice area (EROA), regurgitant volume (RV), and LVEDVi to the benefit of TMVr in the COAPT trial. Design, Setting, and Participants: This post hoc secondary analysis of the COAPT randomized clinical trial performed December 27, 2012, to June 23, 2017, evaluated a subgroup of COAPT patients (group 1) with characteristics consistent with patients enrolled in MITRA-FR (n = 56) (HF with grade 3+ to 4+ SMR, left ventricular ejection fraction of 20%-50%, and New York Heart Association function class II-IV) compared with remaining (group 2) COAPT patients (n = 492) using the end point of ACM or HFH at 24 months, components of the primary end point, and quality of life (QOL) (per the Kansas City Cardiomyopathy Questionnaire overall summary score) and 6-minute walk distance (6MWD). The same end points were evaluated in 6 subgroups of COAPT by combinations of EROA and LVEDVi and of RV relative to LVEDVi. Interventions: Interventions were TMVr plus GDMT vs GDMT alone. Results: A total of 548 participants (mean [SD] age, 71.9 [11.2] years; 351 [64%] male) were included. In group 1, no significant difference was found in the composite rate of ACM or HFH between TMVr plus GDMT vs GDMT alone at 24 months (27.8% vs 33.1%, P = .83) compared with a significant difference at 24 months (31.5% vs 50.2%, P < .001) in group 2. However, patients randomized to receive TMVr vs those treated with GDMT alone had significantly greater improvement in QOL at 12 months (mean [SD] Kansas City Cardiomyopathy Questionnaire summary scores: group 1: 18.36 [5.38] vs 0.43 [4.00] points; P = .01; group 2: 16.54 [1.57] vs 5.78 [1.82] points; P < .001). Group 1 TMVr-randomized patients vs those treated with GDMT alone also had significantly greater improvement in 6MWD at 12 months (mean [SD] paired improvement: 39.0 [28.6] vs -48.0 [18.6] m; P = .02). Group 2 TMVr-randomized patients vs those treated with GDMT alone tended to have greater improvement in 6MWD at 12 months, but the difference did not reach statistical significance (mean [SD] paired improvement: 35.0 [7.7] vs 16.0 [9.1] m; P = .11). Conclusions and Relevance: A small subgroup of COAPT-resembling patients enrolled in MITRA-FR did not achieve improvement in ACM or HFH at 24 months but had a significant benefit on patient-centered outcomes (eg, QOL and 6MWD). Further subgroup analyses with 24-month follow-up suggest that the benefit of TMVr is not fully supported by the proportionate-disproportionate hypothesis. Trial Registration: ClinicalTrials.gov Identifier: NCT01626079.

Morpho-functional changes of cardiac telocytes in isolated atrial amyloidosis in patients with atrial fibrillation.

Telocytes are interstitial cells with long, thin processes by which they contact each other and form a network in the interstitium. Myocardial remodeling of adult patients with different forms of atrial fibrillation (AF) occurs with an increase in fibrosis, age-related isolated atrial amyloidosis (IAA), cardiomyocyte hypertrophy and myolysis. This study aimed to determine the ultrastructural and immunohistochemical features of cardiac telocytes in patients with AF and AF + IAA. IAA associated with accumulation of atrial natriuretic factor was detected in 4.3-25% biopsies of left (LAA) and 21.7-41.7% of right (RAA) atrial appendage myocardium. Telocytes were identified at ultrastructural level more often in AF + IAA, than in AF group and correlated with AF duration and mitral valve regurgitation. Telocytes had ultrastructural signs of synthetic, proliferative, and phagocytic activity. Telocytes corresponded to CD117+, vimentin+, CD34+, CD44+, CD68+, CD16+, S100-, CD105- immunophenotype. No significant differences in telocytes morphology and immunophenotype were found in patients with various forms of AF. CD68-positive cells were detected more often in AF + IAA than AF group. We assume that in aged AF + IAA patients remodeling of atrial myocardium provoked transformation of telocytes into "transitional forms" combining the morphological and immunohistochemical features with signs of fibroblast-, histiocyte- and endotheliocyte-like cells.

The mitral regurgitation effects of cardiac structure and function in left ventricular noncompaction.

This study evaluated the effects of mitral regurgitation (MR) on cardiac structure and function in left ventricular noncompaction (LVNC) patients. The clinical and cardiovascular magnetic resonance (CMR) data for 182 patients with noncompaction or hypertrabeculation from three institutes were retrospectively included. We analyzed the difference in left ventricular geometry, cardiac function between LVNC patients with and without MR. The results showed that patients with MR had a worse New York Heart Association (NYHA) class and a higher incidence of arrhythmia (P < 0.05). MR occurred in 48.2% of LVNC patients. Compared to LVNC patients without MR, the two-dimensional sphericity index, maximum/minimum end-diastolic ratio and longitudinal shortening in LVNC patients with MR were lower (P < 0.05), and the peak longitudinal strain (PLS) of the global and segmental myocardium were obviously reduced (P < 0.05). No significant difference was found in strain in LVNC patients with different degree of MR; end diastolic volume, end systolic volume, and global PLS were statistically associated with MR and NYHA class (P < 0.05), but the non-compacted to compacted myocardium ratio had no significant correlation with them. In conclusion, the presence of MR is common in LVNC patients. LVNC patients with MR feature more severe morphological and functional changes. Hypertrabeculation is not an important factor affecting structure and function at the heart failure stage.

Paroxysmal Severe Mitral Regurgitation.

OBJECTIVE: To investigate the clinical presentation, pathophysiology, and treatment for "paroxysmal severe mitral regurgitation" (MR), which is an underappreciated cause of heart failure with preserved left ventricular ejection fraction. METHODS: We retrospectively reviewed cases of transient severe MR that were evaluated at Mayo Clinic in Rochester, Minnesota, between January 1, 2006, and December 31, 2019. Paroxysmal severe MR was defined as the appearance of transient severe MR in patients with mild MR at rest, normal left ventricle (LV) size, left ventricular ejection fraction greater than 40%, and absence of obstructive coronary artery disease. RESULTS: We identified 6 patients (5 women) with a median age of 68 years. There were 3 distinct mechanisms of paroxysmal severe MR, which we labeled types 1, 2, and 3. Type 1 MR was caused by LV dyssynchrony from a rate-dependent left bundle branch block, which led to apical leaflet tenting and incomplete coaptation. Type 2 MR occurred from mitral annular dilatation during maneuvers that increased left-sided volume. Type 3 MR was caused by coronary artery vasospasm with apical leaflet tenting. Treatments varied depending on the underlying cause and included cardiac resynchronization therapy for type 1, surgical valve replacement for type 2, and medical therapy for type 3. CONCLUSION: Paroxysmal severe MR is a rare cause of heart failure in patients with preserved LV function. We have identified 3 distinct mechanisms that can lead to this dynamic process, with treatments varying based on the underlying cause.

Multimodality imaging assessment of mitral annular disjunction in mitral valve prolapse.

OBJECTIVE: Mitral annular disjunction (MAD) is an abnormality linked to mitral valve prolapse (MVP), possibly associated with malignant ventricular arrhythmias. We assessed the agreement among different imaging techniques for MAD identification and measurement. METHODS: 131 patients with MVP and significant mitral regurgitation undergoing transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) were retrospectively enrolled. Transoesophageal echocardiography (TOE) was available in 106 patients. MAD was evaluated in standard long-axis views (four-chamber, two-chamber, three-chamber) by each technique. RESULTS: Considering any-length MAD, MAD prevalence was 17.3%, 25.5%, 42.0% by TTE, TOE and CMR, respectively (p<0.05). The agreement on MAD identification was moderate between TTE and CMR (κ=0.54, 95% CI 0.49 to 0.59) and good between TOE and CMR (κ=0.79, 95% CI 0.74 to 0.84). Assuming CMR as reference and according to different cut-off values for MAD (≥2 mm, ≥4 mm, ≥6 mm), specificity (95% CI) of TTE and TOE was 99.6 (99.0 to 100.0)% and 98.7 (97.4 to 100.0)%; 99.3 (98.4 to 100.0)% and 97.6 (95.8 to 99.4)%; 97.8 (96.2 to 99.3)% and 93.2 (90.3 to 96.1)%, respectively; sensitivity (95% CI) was 43.1 (37.8 to 48.4)% and 74.5 (69.4 to 79.5)%; 54.0 (48.7 to 59.3)% and 88.9 (85.2 to 92.5)%; 88.0 (84.5 to 91.5)% and 100.0 (100.0 to 100.0)%, respectively. MAD length was 8.0 (7.0-10.0), 7.0 (5.0-8.0], 5.0 (4.0-7.0) mm, respectively by TTE, TOE and CMR. Agreement on MAD measurement was moderate between TTE and CMR (ρ=0.73) and strong between TOE and CMR (ρ=0.86). CONCLUSIONS: An integrated imaging approach could be necessary for a comprehensive assessment of patients with MVP and symptoms suggestive for arrhythmias. If echocardiography is fundamental for the anatomic and haemodynamic characterisation of the MV disease, CMR may better identify small length MAD as well as myocardial fibrosis.

Interactive editing of virtual chordae tendineae for the simulation of the mitral valve in a decision support system.

PURPOSE: Decision support systems for mitral valve disease are an important step toward personalized surgery planning. A simulation of the mitral valve apparatus is required for decision support. Building a model of the chordae tendineae is an essential component of a mitral valve simulation. Due to image quality and artifacts, the chordae tendineae cannot be reliably detected in medical imaging. METHODS: Using the position-based dynamics framework, we are able to realistically simulate the opening and closing of the mitral valve. Here, we present a heuristic method for building an initial chordae model needed for a successful simulation. In addition to the heuristic, we present an interactive editor to refine the chordae model and to further improve pathology reproduction as well as geometric approximation of the closed valve. RESULTS: For evaluation, five mitral valves were reconstructed based on image sequences of patients scheduled for mitral valve surgery. We evaluated the approximation of the closed valves using either just the heuristic chordae model or a manually refined model. Using the manually refined models, prolapse was correctly reproduced in four of the five cases compared to two of the five cases when using the heuristic. In addition, using the editor improved the approximation in four cases. CONCLUSIONS: Our approach is suitable to create realistically parameterized mitral valve apparatus reconstructions for the simulation of normally and abnormally closing valves in a decision support system.