Mitral Prolapse Research Articles

Prognostic Efficacy of Complete Blood Count Indices for Assessing the Presence and the Progression of Myxomatous Mitral Valve Disease in Dogs.

This study investigated the complete blood count (CBC) indices, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) in dogs with myxomatous mitral valve disease (MMVD) and analyzed their correlation with conventional biomarkers, as well as the effect of CBC indices on survival time in dogs with MMVD. Medical records of 75 healthy controls and 249 dogs with MMVD from March 2015 to October 2022 were analyzed. The NLR, MLR, and PLR were calculated by dividing the absolute counts of the CBC parameters. Dogs with MMVD had significantly higher NLR, MLR, and PLR than healthy dogs (all p < 0.0001), especially those in the symptomatic MMVD group with pulmonary edema (p < 0.0001, p = 0.0002, and p = 0.0387, respectively). The NLR and MLR were significantly correlated with N-terminal pro-B type natriuretic peptide levels (both p < 0.0001). The CBC indices showed potential as biomarkers for detecting the presence of MMVD (all p < 0.0001) and severity of MMVD (p < 0.0001, p < 0.0001, and p = 0.006, respectively) using receiver operating characteristic curve analysis. The negative effects of increased NLR, MLR, and PLR on survival were confirmed using Kaplan-Meier curve analysis. In conclusion, NLR, MLR, and PLR could be cost-effective and readily available potential diagnostic and prognostic biomarkers for MMVD in dogs.

Are children with mitral valve prolapse more anxious?

Mitral valve prolapse (MVP) is a common valvular disease in children. Symptoms in children with MVP are not explained by the severity of mitral regurgitation alone. Hence, we sought to correlate symptom status with the incidence of anxiety disorder in this population. Groups were as follows: (a) MVP; n = 115; mean age: 13.5 ± 3.06 years and (b) control; n = 53; mean age: 15.1 ± 13.2. The Screen for Child Anxiety-Related Emotional Disorders (SCAREDs) scale was filled by all participants. The SCARED scores of 25 and above determined a warning for anxiety disorders. The mean SCARED scale values of MVP and control groups were 29.2 ± 13.08 and 24.9 ± 14.17, respectively (P = 0.065). Although the SCARED scale score was higher among the MVP patients, no significant difference was found between the groups in terms of the mean SCARED score, or the number of participants with a score of 25 or more. While girls with MVP had higher anxiety scores compared to boys with the disorder, there was no difference with respect to SCARED scores in children with MVP and the general population when analyzed separately by gender. Moreover, the SCARED scale score was significantly higher in symptomatic MVP patients than in asymptomatic cases. Children with MVP did not have higher anxiety scores compared to those without the syndrome. However, MVP patients with higher anxiety scores may benefit from a psychiatric assessment since higher scores correlate with symptoms.

Genetic mechanisms underlying arrhythmogenic mitral valve prolapse: Current and future perspectives.

Mitral valve prolapse (MVP) is a heart valve disease that is often familial, affecting 2%-3% of the general population. MVP with or without mitral regurgitation can be associated with an increased risk of ventricular arrhythmias and sudden cardiac death (SCD). Research on familial MVP has specifically focused on genetic factors, which may explain the heritable component of the disease estimated to be present in 20%-35%. Furthermore, the structural and electrophysiological substrates underlying SCD/ventricular arrhythmia risk in MVP have been studied postmortem and in the electrophysiology laboratory, respectively. Understanding how familial MVP and rhythm disorders are related may help patients with MVP by individualizing risk and working to develop effective management strategies. This contemporary, state-of-the-art, expert review focuses on genetic factors and familial components that underlie MVP and arrhythmia and encapsulates clinical, genetic, and electrophysiological issues that should be the objectives of future research.

Prevalence and consequences of mitral annular disjunction and Pickelhaude sign in children with mitral valve prolapse

Prevalence and consequences of mitral annular disjunction and Pickelhaude sign in children with mitral valve prolapse

Machine learning-based risk prediction model for canine myxomatous mitral valve disease using electronic health record data.

Myxomatous mitral valve disease (MMVD) is the most common cause of heart failure in dogs, and assessing the risk of heart failure in dogs with MMVD is often challenging. Machine learning applied to electronic health records (EHRs) is an effective tool for predicting prognosis in the medical field. This study aimed to develop machine learning-based heart failure risk prediction models for dogs with MMVD using a dataset of EHRs. A total of 143 dogs with MMVD between May 2018 and May 2022. Complete medical records were reviewed for all patients. Demographic data, radiographic measurements, echocardiographic values, and laboratory results were obtained from the clinical database. Four machine-learning algorithms (random forest, K-nearest neighbors, naïve Bayes, support vector machine) were used to develop risk prediction models. Model performance was represented by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). The best-performing model was chosen for the feature-ranking process. The random forest model showed superior performance to the other models (AUC = 0.88), while the performance of the K-nearest neighbors model showed the lowest performance (AUC = 0.69). The top three models showed excellent performance (AUC ≥ 0.8). According to the random forest algorithm's feature ranking, echocardiographic and radiographic variables had the highest predictive values for heart failure, followed by packed cell volume (PCV) and respiratory rates. Among the electrolyte variables, chloride had the highest predictive value for heart failure. These machine-learning models will enable clinicians to support decision-making in estimating the prognosis of patients with MMVD.

224 Surgical Repair of Mitral Valve Prolapse: Hypertension and Other Determinants of Failure

Abstract Aim It has been postulated that hypertension is associated with an increased likelihood of repair failure in patients with mitral valve prolapse. This study aims to assess whether there is a significant association between hypertension and disease recurrence and need for reoperation. Method A retrospective observational cohort study was conducted at a single centre in the United Kingdom. Patients who underwent surgical repair for mitral valve prolapse were identified between January 2011 and December 2020, with follow-up data collected to December 2021. Patients were classified as hypertensive if they had a pre- operative clinic blood pressure of 140/90 mm Hg or above. Treatment failure was confirmed by the presence of moderate or worse regurgitation on post-operative echocardiography and/or need for reoperation. Multivariate logistic regression and Cox regression were used for statistical analysis. Results A total of 278 patients were identified who had pre-operative blood pressure data available, of those 144 were hypertensive. By the conclusion of the study period, treatment failure occurred in 11.5% of the study sample. No significant association was identified between the presence of hypertension and treatment failure, or time to treatment failure. Concomitant atrial ablation was, however, found to be protective against treatment failure (odds ratio, 6.1; 95% confidence interval, 1.2 to 32.8) and associated with longer time to treatment failure (hazard ratio, 6.3; 95% confidence interval, 1.6 to 25.1). Conclusions There is insufficient evidence to demonstrate that hypertension is associated with treatment failure or time to treatment failure for patients undergoing surgical repair for mitral valve prolapse.

Mitral valve aneurysms: echocardiographic characteristics, formation mechanisms, and patient outcomes.

The accurate etiology of mitral valve aneurysm (MVA) formation is not completely understood, and the most effective management approach for this condition remains controversial. We retrospectively analyzed 20 MVA patients who underwent either surgical interventions or conservative follow-ups at the Zhongnan Hospital of Wuhan University between 2017 and 2021. We examined their clinical, echocardiographic, and surgical records and tracked their long-term outcomes. Of the 20 patients, 12 were diagnosed with MVA using transthoracic echocardiography, seven required additional transesophageal echocardiography for a more definitive diagnosis, and one child was diagnosed during surgery. In all these patients, the MVAs were detected in the anterior mitral leaflet. We found that 15 patients (75%) were associated with infective endocarditis (IE), whereas the remaining patients were associated with bicuspid aortic valve and moderate aortic regurgitation (AR) and mild aortic stenosis (5%), congenital heart disease (5%), elderly calcified valvular disease (5%), mitral valve prolapse (5%), and unknown reasons (5%). Of the 17 patients who underwent hospital surgical interventions, two died due to severe cardiac events. The remaining 15 patients had successful surgeries and were followed up for an average of 13.0 ± 1.8 months. We observed an improvement in their New York Heart Association functional class and mitral regurgitation and AR degrees (P-value < 0.001). During follow-up, only one infant had an increased left ventricular end-diastolic diameter and left ventricular end-systolic diameter, whereas the remaining 14 patients had decreased values (P < 0.001). In addition, none of the three conservatively managed patients experienced disease progression during the 7-24 months of follow-up. We recommend using echocardiography as a highly sensitive method for MVA diagnosis. Although most cases are associated with IE or AR, certain cases still require further study to determine their causes. A prompt diagnosis of MVA in patients using echocardiography can aid in its timely management.

Evaluation of progression of chronic kidney disease in dogs with myxomatous mitral valve disease.

Cardiovascular and renal diseases are known to affect each other in the cardiovascular renal axis disorder (CvRD). Although CvRD, which includes myxomatous mitral valve disease (MMVD) and chronic kidney disease (CKD), has been described in dogs, there are only a few reports on the progression of CKD in accordance with the severity of MMVD. The aim of this study was to evaluate whether the presence of MMVD is associated with the rate of progression of CKD in dogs. The time from the initial diagnosis to the worsening of the International Renal Interest Society (IRIS) stage and the time for the occurrence of hyperphosphatemia and isosthenuria were evaluated. In this retrospective study, CKD progression was determined as an increase in the IRIS stage by at least one level and the development of hyperphosphatemia or isosthenuria. The CKD progression was compared in dogs with and without comorbid MMVD. Dogs with CKD were divided into two groups: dogs with and without MMVD (n = 63, concurrent group; n = 52, CKD group, respectively). The concurrent group was further divided into two subgroups based on the American College of Veterinary Internal Medicine guidelines (B1 group, n = 24; B2 group, n = 39). The time for progression of CKD from IRIS stage 1 to IRIS stage 2 was significantly shorter in the concurrent group than in the CKD group (log-rank test, p < 0.001). MMVD was associated with an increased risk of progression from stage 1 to stage 2 (hazard ratio, 6.442; 95% confidence interval (CI), 2.354 to 18.850; p < 0.001). The timing of the onset of hyperphosphatemia or isosthenuria in the concurrent group and the CKD group was not significantly different. The results of this study suggest that MMVD could be a risk factor for the progression of CKD. Our findings may help predict the prognosis of dogs with both CKD and MMVD compared to CKD only.

The Thoracic Inlet Length as a Reference Point to Radiographically Assess Cardiac Enlargement in Dogs with Myxomatous Mitral Valve Disease.

The diagnostic value of the vertebral heart size (VHS) in dogs with mitral valve degeneration (MVD) is compromised when middle thoracic vertebral anomalies are present. The objective of this study was to assess the use of the thoracic inlet heart score (TIHS) to identify left heart enlargement (LHE) secondary to MVD. The cardiac silhouette of 50 clinically healthy dogs and 106 MVD dogs in different stages was assessed on a right lateral chest radiograph. The TIHS and VHS value were calculated for each patient and compared. The TIHS was significantly different between the control dogs and the dogs with MMVD, increasing with disease stage, control 2.91 ± 0.23, Stage B1 2.98 ± 0.36, B2 3.25 ± 0.34, and C 3.53 ± 0.36, p < 0.05. A THIS ≥3.3 showed 69% sensitivity and 81% specificity to identify LHE. The TIHS showed moderate correlation with the VHS, LA/Ao, and LVIDDN 0.59, 0.42, and 0.62, respectively. The intraobserver and interobserver agreement were almost perfect, 0.96, and substantial, 0.73. The TIHS method can be used to identify LHE secondary to MMVD on dogs' thoracic radiographs.

Effectiveness of the risk stratification proposed by the 2022 European Heart Rhythm Association Expert Consensus statement on arrhythmic mitral valve prolapse

Recently, an expert consensus statement proposed indications where implantation of a primary prevention implantable cardioverter-defibrillator (ICD) may be reasonable in patients with mitral valve prolapse (MVP). The objective was to evaluate the proposed risk stratification by the expert consensus statement. Consecutive patients with MVP without alternative arrhythmic substrates with cardiac magnetic resonance imaging (CMR) were included in a single-center retrospective registry. Arrhythmic MVP (AMVP) was defined as a total premature ventricular complex burden ≥5%, non-sustained ventricular tachycardia (VT), VT, or ventricular fibrillation. The end point was a composite of SCD, VT, inducible VT, and appropriate ICD shocks. In total, 169 patients (52.1% male, median age 51.4 years) were included and 99 (58.6%) were classified as AMVP. Multivariate logistic regression identified the presence of late gadolinium enhancement (OR 2.82, 95%CI 1.45-5.50) and mitral annular disjunction (OR 1.98, 95%CI 1.02-3.86) as only predictors of AMVP. According to the EHRA risk stratification, 5 patients with AMVP (5.1%) had a secondary prevention ICD indication, while in 69 patients (69.7%) the implantation of an ICD may be reasonable. During a median follow-up of 8.0 years (IQR 5.0-15.6), the incidence rate for the composite arrhythmic end point was 0.3%/year (95%CI 0.1-0.8). More than half of MVP patients referred for CMR met the AMVP diagnostic criteria. Despite low long-term event rates, in 70% of patients with AMVP the implantation of an ICD may be reasonable. Risk stratification of SCD in MVP remains an important knowledge gap and requires urgent investigation.

Galectin-3 is able to differentiate dogs with myxomatous mitral valve disease from healthy control dogs.

Galectin-3 is a cardiac biomarker for heart failure in humans. However, it has not been investigated in dogs with naturally occurring heart disease. This study aimed to compare plasma galectin-3 concentration in healthy dogs and those with myxomatous mitral valve disease (MMVD) and explore the potential association of galectin-3 with other cardiac biomarkers, inflammatory cytokines, echocardiographic estimates, and dog characteristics. 10 healthy dogs and 30 dogs with MMVD were prospectively recruited. In this case-control study, plasma galectin-3, inflammatory cytokines, echocardiographic estimates, and other cardiac biomarkers were measured, and dog characteristics were recorded. Plasma galectin-3 concentration was significantly higher in dogs with MMVD (2.94 [interquartile range, 1.61 to 5.20] ng/mL) than in healthy controls (1.56 [0.69 to 1.84] ng/mL, P = .009). Logistic regression analysis revealed that galectin-3 concentration and age predicted the presence of MMVD (predictive accuracy = 90.0%, P < .05). A cut-off value ≥ 1.9 ng/mL for galectin-3 differentiated healthy dogs from dogs with MMVD (70% sensitivity; 90% specificity AUC, 0.77; P = .01). Plasma galectin-3 concentration was higher in dogs with MMVD than in healthy dogs, indicating that it is a novel cardiac biomarker in dogs with MMVD although there was no significant difference between MMVD stages.

PROX1 Inhibits PDGF-B Expression to Prevent Myxomatous Degeneration of Heart Valves.

Cardiac valve disease is observed in 2.5% of the general population and 10% of the elderly people. Effective pharmacological treatments are currently not available, and patients with severe cardiac valve disease require surgery. PROX1 (prospero-related homeobox transcription factor 1) and FOXC2 (Forkhead box C2 transcription factor) are transcription factors that are required for the development of lymphatic and venous valves. We found that PROX1 and FOXC2 are expressed in a subset of valvular endothelial cells (VECs) that are located on the downstream (fibrosa) side of cardiac valves. Whether PROX1 and FOXC2 regulate cardiac valve development and disease is not known. We used histology, electron microscopy, and echocardiography to investigate the structure and functioning of heart valves from Prox1ΔVEC mice in which Prox1 was conditionally deleted from VECs. Isolated valve endothelial cells and valve interstitial cells were used to identify the molecular mechanisms in vitro, which were tested in vivo by RNAScope, additional mouse models, and pharmacological approaches. The significance of our findings was tested by evaluation of human samples of mitral valve prolapse and aortic valve insufficiency. Histological analysis revealed that the aortic and mitral valves of Prox1ΔVEC mice become progressively thick and myxomatous. Echocardiography revealed that the aortic valves of Prox1ΔVEC mice are stenotic. FOXC2 was downregulated and PDGF-B (platelet-derived growth factor-B) was upregulated in the VECs of Prox1ΔVEC mice. Conditional knockdown of FOXC2 and conditional overexpression of PDGF-B in VECs recapitulated the phenotype of Prox1ΔVEC mice. PDGF-B was also increased in mice lacking FOXC2 and in human mitral valve prolapse and insufficient aortic valve samples. Pharmacological inhibition of PDGF-B signaling with imatinib partially ameliorated the valve defects of Prox1ΔVEC mice. PROX1 antagonizes PDGF-B signaling partially via FOXC2 to maintain the extracellular matrix composition and prevent myxomatous degeneration of cardiac valves.

Neochordae implantation versus leaflet resection in mitral valve posterior leaflet prolapse and dilated left ventricle: a propensity score matching comparison with long-term follow-up.

Uncorrected severe mitral regurgitation (MR) due to posterior prolapse leads to left ventricular dilatation. At this stage, mitral valve repair becomes mandatory to avoid permanent myocardial injury. However, which technique among neochoardae implantation and leaflet resection provides the best results in this scenario remains unknown. We selected 332 patients with left ventricular dilatation and severe degenerative MR due to posterior leaflet (PL) prolapse who underwent neochoardae implantation (85 patients) or PL resection (247 patients) at our institution between 2008 and 2020. A propensity score matching analysis was carried on to decrease the differences at baseline. Matching yielded 85 neochordae implantations and 85 PL resections. At 10 years, freedom from cardiac death and freedom from mitral valve reoperation were 92.6 ± 6.1% vs 97.8 ± 2.1% and 97.7 ± 2.2% vs 95 ± 3% in the neochordae group and in the PL resection group, respectively. The MR ≥2+ recurrence rate was 23.9 ± 10% in the neochordae group and 20.8 ± 5.8% in the PL resection group (P = 0.834) at 10 years. At the last follow-up, the neochordae group showed a higher reduction of left ventricular end-diastolic diameter (44 vs 48 mm; P = 0.001) and a better ejection fraction (60% vs 55%; P < 0.001) compared to PL resection group. In this subgroup of patients, both neochordae implantation and leaflet resection provide excellent durability of the repair in the long term. Neochordae implantation might have a better effect on dilated left ventricle.

Abstract P2100: Highly Localized Myocardial Expression Of Brain Natriuretic Peptide In Patients With Mitral Valve Prolapse

Mitral valve prolapse (MVP) is a common cause of mitral regurgitation (MR), adverse left ventricular (LV) remodeling and arrhythmias. MVP induces mechanical stretch to the inferobasal (INF) myocardium and papillary muscles. The underlying regional and molecular pathology of MVP-induced LV remodeling remains incompletely understood. The aim was to characterize the molecular effects of mechanical stretch by comparing the regional gene expression of the INF region of LV in patients with MVP. Biopsies were obtained from the INF LV and the interventricular septum during mitral valve repair surgery for MVP-induced primary MR. Spatial transcriptome sequencing results correlated with histological staining of fibrosis in the INF and septal regions (R=0.97, P&lt;0.0001). The extent of fibrosis was similar between the INF region and the septal control in the respective patients with MVP. The localized fibrotic areas of the INF region showed decreased expression of cardiac myocyte genes and increased expression of fibrous and EndMT markers. In the INF region, we identified a transition zone between healthy myocardium and fibrous tissue. This transition zone showed increased expression of the NPPB gene encoding brain natriuretic peptide (BNP), whereas NPPB was not increased in the septal region of the same patients, and was confirmed by qPCR (NPPB +6.4-fold, N=11, P=0.004). The INF border zone is characterized by increase expression of NPPB, IGFBP2 and MFGE8, which have been described to be associated with adverse LV remodeling in heart failure. The serum NT-proBNP levels (mean 276.8 ± 121.6 pg/ml) of the patients correlated with NPPB levels from the INF region (R=0.76, P=0.01, N=9), whereas no correlation was found with NPPB levels from the septal control regions (R=0.17, P=0.65) of the same patients. In conclusion, spatial transcriptome analysis in MVP patients identifies a transition zone of the INF region of LV which is exposed to high mechanical stretch. This localized transition zone has a specific gene expression profile, e.g. with increased NBBP expression that correlates with increased NT-ProBNP serum concentrations. Our results indicate that mechanical stretch induces highly localized myocardial pathologies with systemic consequences.

Abstract P1012: Wnt Signaling Is Required For Myxomatous Valve Disease In A Mouse Model Of Marfan Syndrome

Introduction: Myxomatous valve disease (MVD) is the most common cause of mitral regurgitation, characterized by valve leaflet thickening and progressive valve degeneration, leading to impaired cardiac function and heart failure. MVD in a mouse model of Marfan syndrome (MFS) includes valve leaflet thickening and increased immune cell infiltration. However, the underlying mechanisms by which immune cells are recruited in MFS valves remain undefined. Hypothesis: Inhibition of Wnt signaling prevents immune cell recruitment and MVD progression in MFS valves. Methods: Mice with the mutation of Fibrillin 1 ( Fbn1 C1039G/+ ) recapitulate histopathological features of MFS and Wnt signaling activity was detected in TCF/Lef-lacZ reporter mice. The expression level of C-C motif chemokine ligand 2 (CCL2) was detected in Fbn1 C1039G/+ mice by qPCR and RNAscope. Inhibition of Wnt signaling was achieved by conditional induction of the soluble Wnt inhibitor Dkk1 in periostin-expressing valve interstitial cells of Periostin-Cre; tetO-Dkk1; R26rtTA; TCF/Lef-lacZ; Fbn1 C1039G/+ mice. Dietary doxycycline was administered for one month beginning with MVD initiation (1-month-old) or MVD progression (2-month-old). Histological evaluation and immunofluorescence for immune cells were performed. Results: Wnt signaling as detected by TCF/Lef-lacZ reporters and CCL2 expression were upregulated early in mitral valve disease progression, prior to immune cell infiltration in Fbn1 C1039G/+ mice. Inhibition of Wnt signaling by Dkk1 induction at 1-month of age prevented the induction of myxomatous mitral valve disease, indicated by reduced valve leaflet thickness with decreased CD45+ leukocytes and CCR2+ immune cells in Fbn1 C1039G/+ mice. However, later Wnt inhibition starting at 2 months when inflammation and myxomatous changes are occurring did not prevent the progression of myxomatous mitral valve disease. Conclusions: Wnt signaling is involved in the initiation of mitral valve abnormalities and inflammation, but is not responsible for valve disease progression once it has been initiated.

Abstract P2114: Chromatin Accessibility Governs Mechanosensitive Gene Expression In Cardiac Fibroblasts

Objective: We recently demonstrated regionalized myocardial fibrosis in patients undergoing surgical repair for Mitral Valve Prolapse. The location of fibrosis suggests a mechanically driven process wherein mechanical stress alters the phenotype of ventricular fibroblasts to promote an increase in tissue stiffness, eventually causing establishment of a fibrotic scar. We sought to better understand how mechanical stiffness affected cellular programs. Methods: We cultured primary human cardiac fibroblasts derived from the same patient on a mechanically stiff (TC Plastic, ~2GPa), as well as a mechanically soft (2kPa) substrate and then performed immunofluorescence, western blotting, RNA Seq, and ATAC Seq. Following differential analysis of omics data, we performed an integration analysis by filterinig differentially accessible chromatin to only include sites that fell within 10 kB of opened/closed chromatin. Finally, we performed a motif enrichment analysis using the online bioinformatics package Homer. Results: Immunofluorescence and western blotting revealed that cells cultured on a stiff substrate expressed canonical markers of fibroblast activation compared with soft substrates (alpha SMA, COL1A1, P&lt;0.0001). RNA Sequencing revealed differential changes in 1615 genes in fibroblasts (FDR adjusted P&lt;1.6*10 -6 ), several of which were subsequently validated using western blot. ATAC Seq identified 5855 regions across the genome which opened/closed in response to different mechanical environments in fibroblasts (adjusted P&lt;0.05). Integrating these datasets revealed 803 Chromatin changes that fell within 10kb of differentially expressed genes, with AP1 and TEAD family transcription factors predicted to be master regulators of closing and opening chromatin, respectively. Proof-of-concept motif validation conducted on differentially expressed chromatin within intron 12 of the MYH10 gene demonstrated presence of a transcriptional repressor with evidence of JunD as a binding partner for this site. Conclusions: The mechanical environment plays a major role in cellular phenotype and regulates chromatin organization and expression of pro-fibrotic genes through changes in chromatin accessibility.

Mitral Annular Disjunction: A Scoping Review.

Mitral annular disjunction (MAD) is the atrial displacement of the mitral valve (MV) hinge point, especially along the posterior mitral leaflet, which leads to inhomogeneous blood flow into the left ventricle, causing chronic fibrotic changes, malignant arrhythmias, and even sudden cardiac arrest. Some studies suggest that MAD is a part of normal heart morphology; however, the origin is still controversial. MAD commonly occurs with MV prolapse and myxomatous degenerative MV disease. In almost 20% of cases, MAD can occur independently as well. The prevalence of MAD in normal hearts varies from 8.6% to 96%, depending on the imaging modality and the cutoff used to define MAD. Transthoracic echocardiography is often the initial screening test, but the low sensitivity of transthoracic echocardiography to identify MAD makes it easy to miss the diagnosis altogether. More advanced imaging, especially cardiac MRI, is the gold standard for diagnosing MAD and risk stratification. MAD is an independent predictor of malignant arrhythmia. Among patients with MAD, risk stratification is based on the age at diagnosis, previous syncopal attacks, premature ventricular contractions, papillary muscle fibrosis, and longitudinal disjunction distance. Most asymptomatic patients are managed conservatively; however, radiofrequency ablation should be considered in patients with high-risk or symptomatic MAD due to the risk of ventricular arrhythmias and sudden cardiac death.

Pyoderma gangrenosum with Marfan syndrome and Crohn’s disease: A rare association

A 22-year-old man presented with multiple, painful ulcers on the thighs, legs, and face of 10-day duration and diarrhea and bleeding per rectum of 2-year duration. The ulcers were tender and had a peripheral violaceous border. General examination revealed tall stature, long extremities, kyphosis, arachnodactyly, and hyperextensible wrist and thumbs. The arm span was more than the height and the thumb sign and wrist sign were positive, diagnostic of Marfan syndrome. Skin biopsy from the edge of the ulcer showed infiltrates of neutrophils and lymphocytes in the dermis and subcutaneous tissue. A detailed evaluation ruled out other causes for skin ulceration and we made a diagnosis of pyoderma gangrenosum. Echocardiogram demonstrated mitral valve prolapse. Computed tomography of abdomen showed segmental mucosal thickening as skip lesions in the colon and rectum. Endoscopy showed chronic colitis with multiple punched out ulcers. Colonic biopsy showed noncaseating granulomas suggestive of Crohn’s disease. Although inflammatory bowel disease is a well-known association of pyoderma gangrenosum, we did not come across any previous reports of coexistence of pyoderma gangrenosum, Crohn’s disease, and Marfan syndrome.

Sudden Death Due to Myxomatous Degeneration of Cardiac Valves: A Case Report

Sudden death occurs from unnatural as well as from natural causes. Forensic pathologists usually encountercases of sudden death which occurred in apparently healthy individuals under suspicious circumstances. Most ofthe cases have known history of a natural diseases but unfortunately in few cases, the pathology is revealed onlyduring autopsy. We report a case of sudden death due to mitral valve prolapse in a young boy during a scuffleafter sustaining a trivial trauma

Emergency caesarean section of a patient diagnosed with mitral valve prolapse with twin gestation, acute pulmonary oedema and late-onset preeclampsia - A case report.

Emergency caesarean section of a patient diagnosed with mitral valve prolapse with twin gestation, acute pulmonary oedema and late-onset preeclampsia - A case report.