Mitral Prolapse Research Articles

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.

Mitral valve prolapse and sudden cardiac death

Mitral valve prolapse and sudden cardiac death

Correlation between the Leaflet-Annulus Index and Echocardiographic Indices in Maltese Dogs with Myxomatous Mitral Valve Disease.

Myxomatous mitral valve disease (MMVD) is the most common chronic heart valve disease, leading to left-sided cardiomegaly in dogs. The leaflet-annulus index (LAI) was originally used in humans as a predictor of mitral regurgitation (MR) after mitral valve repair surgery. This index represents the quantity and severity of MR since it is affected by annular dilation. Recently, LAI was adapted to veterinary medicine, and its usefulness as an indicator of annular dilation on 2D transthoracic echocardiography in MMVD dogs was suggested. For this study, 135 Maltese dogs were selected and divided into groups of control, B1, and B2, according to the American College of Veterinary Internal Medicine consensus statement. The following data were collected: radiographic indices including the vertebral heart score and vertebral left atrial size, echocardiographic indices including the left-atrium-to-aortic-root ratio (LA:Ao), left ventricular internal diameter at diastole, normalized for body weight, and anteroposterior length and LAI measured on right parasternal long-axis view. The results showed a significant difference in LAI between each group, becoming smaller as the disease progressed. Also, there was a significant correlation between LAI and each index, showing the strongest correlation with LA:Ao. LAI could be helpful as a new indicator used for the determination of severity and prognosis in Maltese dogs with MMVD.

Barlow syndrome: a diagnostic difficulty

Barlow syndrome: a diagnostic difficulty

The incidence and interrelationship of hemivertebra and concomitant cardiac abnormalities in congenital scoliosis

BackgroundCongenital scoliosis(CS) is associated with multiple organs defect, and cardiac abnormalities have been reported commonly associated with CS. Hemivertebra is caused by the failure of vertebral formation, which is a major constitute of CS. Till now, few studies focus on the incidence and interrelationship of hemivertebra and concomitant cardiac abnormalities in congenital scoliosis. We aimed to analyze the cardiac defect in CS patients with or without hemivertebra, and further explore the incidence of cardiac defect between different types of hemivertebra.MethodsThe ultrasonic cardiography (UCG) results of surgically treated congenital scoliosis (CS) patients between 2015 and 2018 were retrospectively analyzed. Patients were divided into hemivertebra group and non-hemivertebra group according to preoperative CT. Patients with hemivertebra was further divided into sub-group by single/multiple or fully/partially/mixed segmented hemivertebra. Demographic information, radiographic data and cardiac abnormalities were statistically compared between groups.ResultsA total of 329 patients were analyzed, including 216 patients with hemivertebra and 113 patients without hemivertebra. UCG results were abnormal in 89 cases (27.1%), including 41 males(12.5%) and 48 females(14.6%). Hemivertebra group had comparable incidence of cardiac abnormalities with non-hemivertebra group (p = 0.517). No significant difference in the incidence of UCG abnormalities between single and multiple hemivertebra group (P = 0.246). Binary logistic regression analysis showed that female sex with multiple hemivertebra was a risk factor for abnormal UCG (P = 0.009, OR = 3.449). Cardiac abnormalities was comparable among fully, partially and mixed segmented hemivertebra group(P = 0.264). In abnormal UCG, 33 patients with hemivertebra had non-valvular abnormalities, and 48.5% (16/33) were septal defects. 28 patients had valvular abnormalities, most of them were mitral valve abnormalities, especially mitral valve redundancy, prolapse and insufficiency(82.1%, 23/28). No significant difference between the incidence of non-valvular and valvular abnormalities in patients with hemivertebra (P = 0.581).ConclusionsThe incidence of abnormal UCG results was approximately 28.2% in CS patients with hemivertebra. Female patients with multiple hemivertebra had a higher risk of UCG abnormalities. Mitral valve abnormalities were the most common abnormality of UCG found in CS patients with hemivertebra.Trial registrationretrospectively registered.

Secondary leaflet tethering in patients with severe degenerative mitral regurgitation and its association with the severity of mitral regurgitation.

The purpose of the study was to determine the association between vena contracta area (VCA) and secondary leaflet tethering among mitral valve prolapse (MVP) patients, and thus to further identify and characterize an MVP with pathological leaflet tethering (MVPt+) phenotype. We prospectively evaluated 94 consecutive MVP patients with significant mitral regurgitation (MR) and 21 healthy controls. MVPt+ group was defined as tenting volume index (TVi)>.7mL/m2 . The three-dimensional (3D) geometry of mitral valve apparatus and VCA was measured with dedicated quantification software. Of the 94 patients with MVP and significant MR, 31 patients showed a TVi>.7mL/m2 and entered the MVP with leaflet tethering (MVPt+) group. In stepwise multivariate analysis, only prolapse volume index and TVi were independently associated with 3D VCA. 3D VCA, annular area index, and plasma levels of NT-proBNP were independently correlated with the severity of leaflet tethering. ROC curve revealed that a 3D VCA ≥ .55 cm2 is the optimal cutoff point to predict MVPt+ phenotype. Secondary leaflet tethering is a significant mechanism behind severe degenerative MR, resulting in an MVPt+ phenotype featuring more advanced morphological and hemodynamical characteristics.

NRC-Net: Automated noise robust cardio net for detecting valvular cardiac diseases using optimum transformation method with heart sound signals

Objective:Cardiovascular Diseases (CVDs) can be effectively treated when detected early, reducing mortality rates significantly. Traditionally, Phonocardiogram (PCG) signals have been utilized for detecting cardiovascular disease due to their cost-effectiveness and simplicity. Nevertheless, various environmental and physiological noises frequently affect the PCG signals, compromising their essential distinctive characteristics. The prevalence of this issue in overcrowded and resource-constrained hospitals can compromise the accuracy of medical diagnoses. Therefore, this study aims to discover the optimal transformation method for detecting CVDs using noisy heart sound signals and propose a noise-robust network to improve the CVDs classification performance. Methods:For the identification of the optimal transformation method for noisy heart sound data, Mel Frequency Cepstral Coefficients (MFCCs), Short-Time Fourier Transform (STFT), Constant-Q Nonstationary Gabor Transform (CQT), and Continuous Wavelet Transform (CWT) has been used with Visual Geometry Group with 16-layer deep model architecture (VGG16). Furthermore, we propose a novel Convolutional Recurrent Neural Network (CRNN) architecture called Noise Robust Cardio Net (NRC-Net), which is a lightweight model to classify Mitral Regurgitation, Aortic Stenosis, Mitral Stenosis, Mitral Valve Prolapse, and normal heart sounds using PCG signals contaminated with respiratory and random noises. An attention block is included to extract important temporal and spatial features from the noisy corrupted heart sound. Results:The results of this study indicate that CWT is the optimal transformation method for noisy heart sound signals. When evaluated on the GitHub heart sound dataset, CWT demonstrates an accuracy of 95.69% for VGG16, which is 1.95% better than the second-best CQT transformation technique. Moreover, our proposed NRC-Net with CWT obtained an accuracy of 97.4%, which is 1.71% higher than the VGG16. Conclusion:Based on the outcomes illustrated in the paper, the proposed model is robust to noisy data and can be used in polyclinics and hospitals to detect valvular cardiac diseases accurately.

Stroke in mitral valve prolapse: risk factors and left atrial function in cryptogenic versus non-cryptogenic ischemic subtypes.

Mitral valve prolapse (MVP) has been associated with an increased risk of ischemic stroke. Older age, thicker mitral leaflets, and significant mitral regurgitation (MR) leading to atrial fibrillation have been traditionally considered risk factors for ischemic stroke in MVP. However, specific risk factors for MVP-stroke subtypes are not well defined. The aim of this study is to evaluate clinical and echocardiographic parameters, including left atrial (LA) function, in MVP with cryptogenic (C) vs. non-cryptogenic (NC) stroke. In this case-control matched study, MVPs were identified in consecutive echocardiograms obtained after a stroke from January 2013 to December2016 at the University of California, San Francisco. MVP was defined as leaflet displacement ≥2 mm in the parasternal long-axis view at end-systole. Age/gender matched MVPs without stroke and healthy controls without MVP were also identified. We analyzed LA end-systolic/diastolic volume index, emptying fraction (LAEF), function index (LAFI), and global longitudinal strain in all MVPs and controls. We also measured left ventricular (LV) volume indexes, mass index, ejection fraction (EF), degree of MR and leaflet thickness. We identified a total of 30 MVPs (age 70 ± 12, 50% females) with stroke (11 with C- and 19 with NC-stroke), 20 age/gender matched MVPs without a stroke and 16 controls. MVPs without stroke had lower BMI, less hypertension but more MR (≥moderate in 45% vs. 17%), more abnormal LA function (lower LAEF, LAFI) and larger LV volumes/mass (all p < 0.05) when compared to MVPs with stroke. Leaflet thickness was overall mild (<3 mm) and similar in the 2 groups. Within the MVP stroke group, NC-stroke had higher BMI, more hypertension and more atrial fibrillation compared to C-stroke. In the variables tested, patients with C-stroke did not differ from controls. MVP-related MR may be protective against stroke despite abnormal LA function. Risk of NC-stroke in MVP is related to common stroke risk factors rather than mitral valve leaflet thickness. The etiology of C-stroke in MVP warrants further studies.