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Impaired mitochondria cause an impressive decrease in ATP production becoming a common condition of cardiovascular diseases. Myxomatous mitral valve disease (MMVD) is characterized by mitochondrial dysfunction. By a non-invasive procedure of metabolism analysis on peripheral blood mononuclear cells, we exploit ex-vivo studies that directly constitute a translational approach to evaluate the cell bioenergetics. Cell ATP production decreased in the presence of MMVD, whereas glycolysis was unaffected. In MMVD, the mitochondrial activity underwent a significant reduction of basal respiration, maximal respiration, and ATP production. Our results depicted a pathological condition of MMVD characterized by cell metabolism deprived of mitochondrial energy support., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Salvatore Nesci reports financial support was provided by University of Bologna. Chiara Bernardini reports financial support was provided by University of Bologna. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The purpose of this review is to present a comprehensive overview of the literature published up to February 2024 on the PubMed database regarding the development of mitral valve disease, with detailed reference to mitral valve prolapse, from embryology to a genetic profile. Out of the 3291 publications that deal with mitral valve embryology, 215 refer to mitral valve genetics and 83 were selected for further analysis. After reviewing these data, we advocate for the importance of a gene-based therapy that should be available soon, to prevent or treat non-invasively the valvular degeneration., Competing Interests: Declaration of Competing Interest We declare that we are responsible for recognizing any conflict of interest that could bias our work in the acknowledgments, disclosing all financial support and any other personal connections. This paper contains data that have not previously published or not under consideration for publication in other journals., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Ischemic mitral regurgitation (IMR) occurs from incomplete coaptation of the mitral valve (MV) after myocardial infarction (MI), typically worsened by continued remodeling of the left ventricular (LV). The importance of LV remodeling is clear as IMR is induced by the post-MI dual mechanisms of mitral annular dilation and leaflet tethering from papillary muscle (PM) distension via the MV chordae tendineae (MVCT). However, the detailed etiology of IMR remains poorly understood, in large part due to the complex interactions of the MV and the post-MI LV remodeling processes. Given the patient-specific anatomical complexities of the IMR disease processes, simulation-based approaches represent an ideal approach to improve our understanding of this deadly disease. However, development of patient-specific models of left ventricle-mitral valve (LV-MV) interactions in IMR are complicated by the substantial variability and complexity of the MR etiology itself, making it difficult to extract underlying mechanisms from clinical data alone. To address these shortcomings, we developed a detailed ovine LV-MV finite element (FE) model based on extant comprehensive ovine experimental data. First, an extant ovine LV FE model (Sci. Rep. 2021 Jun 29;11(1):13466) was extended to incorporate the MV using a high fidelity ovine in vivo derived MV leaflet geometry. As it is not currently possible to image the MVCT in vivo, a functionally equivalent MVCT network was developed to create the final LV-MV model. Interestingly, in pilot studies, the MV leaflet strains did not agree well with known in vivo MV leaflet strain fields. We then incorporated previously reported MV leaflet prestrains (J. Biomech. Eng. 2023 Nov 1;145(11):111002) in the simulations. The resulting LV-MV model produced excellent agreement with the known in vivo ovine MV leaflet strains and deformed shapes in the normal state. We then simulated the effects of regional acute infarctions of varying sizes and anatomical locations by shutting down the local myocardial contractility. The remaining healthy (noninfarcted) myocardium mechanical behaviors were maintained, but allowed to adjust their active contractile patterns to maintain the prescribed pressure-volume loop behaviors in the acute post-MI state. For all cases studied, the LV-MV simulation demonstrated excellent agreement with known LV and MV in vivo strains and MV regurgitation orifice areas. Infarct location was shown to play a critical role in resultant MV leaflet strain fields. Specifically, extensional deformations of the posterior leaflets occurred in the posterobasal and laterobasal infarcts, while compressive deformations of the anterior leaflet were observed in the anterobasal infarct. Moreover, the simulated posterobasal infarct induced the largest MV regurgitation orifice area, consistent with experimental observations. The present study is the first detailed LV-MV simulation that reveals the important role of MV leaflet prestrain and functionally equivalent MVCT for accurate predictions of LV-MV interactions. Importantly, the current study further underscored simulation-based methods in understanding MV function as an integral part of the LV., (Copyright © 2024 by ASME.)

A precise quantification of mitral regurgitation (MR) severity is essential for treatment and outcome of patients with MR. 3D echocardiography facilitates estimation of MR but selection of patients with necessity of invasive treatment remains challenging. We investigate effective regurgitation orifice area (EROA) quantification by 3D compared to 2D echocardiography in patients with MR and highlight the improved discrimination of MR severity. We consecutively enrolled fifty patients with primary or secondary and at least moderate MR undergoing 2D and 3D colour Doppler echocardiography prior to transcatheter edge-to-edge repair (TEER). Improved accuracy of MR grading using 3D vena contracta area (VCA) as an estimate of EROA was compared to 2D proximal isovelocity surface area (PISA) quantification method and a multiparameter reference standard. Quantification of EROA remarkably varies between 2D and 3D echocardiography and the discrimination between moderate and severe MR was significantly (p = 0.001) different using 2D PISA or 3D VCA, respectively. 3D VCA correlated significantly (r = 0.501, p < 0.001) better with the pre-defined MR severity. We detected crucial differences in the correct identification of severe MR between 2D and 3D techniques, thus 2D PISA significantly (p < 0.0001) underestimates EROA due to clinical and morphological parameters. The assessment of 3D VCA resulted in improved diagnostic accuracy., (© 2024. The Author(s).)

Monoamine oxidases (MAOs), mitochondrial enzymes that constantly produce hydrogen peroxide (H 2 O 2 ) as a byproduct of their activity, have been recently acknowledged as contributors to oxidative stress in cardiometabolic pathologies. The present study aimed to assess whether MAOs are mediators of valvular oxidative stress and interact in vitro with angiotensin 2 (ANG2) to mimic the activation of the renin-angiotensin system. To this aim, valvular tissue samples were harvested from 30 patients diagnosed with severe primary mitral regurgitation and indication for surgical repair. Their reactive oxygen species (ROS) levels were assessed by means of a ferrous oxidation xylenol orange (FOX) assay, while MAO expression was assessed by immune fluorescence (protein) and qRT-PCR (mRNA). The experiments were performed using native valvular tissue acutely incubated or not with angiotensin 2 (ANG2), MAO inhibitors (MAOI) and the angiotensin receptor blocker, irbesartan (Irb). Correlations between oxidative stress and echocardiographic parameters were also analyzed. Ex vivo incubation with ANG2 increased MAO-A and -B expression and ROS generation. The level of valvular oxidative stress was negatively correlated with the left ventricular ejection fraction. MAOI and Irb reduced valvular H 2 O 2. production. In conclusion, both MAO isoforms are expressed in pathological human mitral valves and contribute to local oxidative stress and ventricular functional impairment and can be modulated by the local renin-angiotensin system .

Background: Mitral valve (MV) disease including myxomatous degeneration is the most common form of valvular heart disease with an age-dependent frequency. Genetic evidence indicates that mutations of the human transcription factor FOXC1 are associated with MV defects, including MV regurgitation. In this study, we sought to determine whether murine Foxc1 and its closely related factor, Foxc2 , are required in valvular endothelial cells (VECs) for the maintenance of MV leaflets, including VEC junctions and the stratified trilaminar ECM (extracellular matrix)., Methods: Adult mice carrying tamoxifen-inducible, vascular endothelial cell (EC), and lymphatic EC-specific, compound Foxc1;Foxc2 mutations (ie, EC- Foxc -DKO and lymphatic EC- Foxc -DKO mice, respectively) were used to study the function of Foxc1 and Foxc2 in the maintenance of MVs. The EC and lymphatic EC mutations of Foxc1/c2 were induced at 7 to 8 weeks of age by tamoxifen treatment, and abnormalities in the MVs of these mutant mice were assessed via whole-mount immunostaining, immunohistochemistry/RNAscope, Movat pentachrome/Masson Trichrome staining, and Evans blue injection., Results: EC deletions of Foxc1 and Foxc2 in mice resulted in abnormally extended and thicker MVs by causing defects in the regulation of ECM organization with increased proteoglycan and decreased collagen. Notably, reticular adherens junctions were found in VECs of control MV leaflets, and these reticular structures were severely disrupted in EC- Foxc -DKO mice. PROX1 (prospero homeobox protein 1), a key regulator in a subset of VECs on the fibrosa side of MVs, was downregulated in EC- Foxc1/c2 mutant VECs. Furthermore, we determined the precise location of lymphatic vessels in murine MVs, and these lymphatic vessels were aberrantly expanded and dysfunctional in EC- Foxc1/c2 mutant MVs. Lymphatic EC deletion of Foxc1/c2 also resulted in similar structural/ECM abnormalities as seen in EC- Foxc1/c2 mutant MVs., Conclusions: Our results indicate that Foxc1 and Foxc2 are required for maintaining the integrity of the MV, including VEC junctions, ECM organization, and lymphatic vessel formation/function to prevent myxomatous MV degeneration., Competing Interests: None.

Genetic factors play a significant role in the pathogenesis of mitral valve diseases, including mitral valve prolapse (MVP) and mitral valve regurgitation. Genes like Fibrillin-1 (FBN1), Filamin A (FLNA), matrix metalloproteinase 2 (MMP2), and SRY-box transcription factor 9 (SOX9) are known to influence mitral valve pathology but knowledge of the exact mechanism is far from clear. Data regarding serum parameters, transesophageal echocardiography, and genetic and histopathologic parameters were investigated in 54 patients who underwent cardiovascular surgery for mitral valve regurgitation. The possible association between Fibrillin-1, Filamin A, MMP2, and SOX9 gene expressions was checked in relationship with the parameters of systemic inflammatory response. The mRNA expression levels (RQ-relative quantification) were categorized into three distinct groups: low (RQ < 1), medium/normal (RQ = 1-2), and high (RQ > 2). Severe fibrosis of the mitral valve was reflected by high expression of FBN1 and low expression of MMP2 ( p < 0.05). The myxoid degeneration level was associated with the mRNA expression level for FBN1 and a low lymphocyte-monocyte ratio was associated with an increased mRNA expression of FBN1 ( p < 0.05). A high number of monocytes was associated with high values of FBN1 whereas the increase in the number of lymphocytes was associated with high levels of MMP2. In addition, we observed that the risk of severe hyalinization was enhanced by a low mRNA expression of FLNA and/or SOX9. In conclusion, a lower FLNA mRNA expression can reflect the aging process that is highlighted in mitral valve pathology as a higher risk for hyalinization, especially in males, that might be prevented by upregulation of the SOX9 gene. FBN1 and MMP2 influence the inflammation-related fibrotic degeneration of the mitral valve. Understanding the genetic base of mitral valve pathology can provide insights into disease mechanisms, risk stratification, and potential therapeutic targets.

Atrioventricular (AV) valve disease is a major burden in our Indian subcontinent, where rheumatic heart disease is still prevalent, when compared to the Western world, where degenerative heart disease is more prevalent. Worldwide, nearly 300,000 valve replacements are done every year but not without complications. These challenges can be multidimensional and multiscalar with the macroscopic and microscopic properties of the native patient tissue interacting with the mechanical and bioprosthetic heart valves and rings. Understanding the complex and variable anatomy of the AV valves is essential to know the exact pathophysiology of the disease and to decide the treatment of choice., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Degenerative mitral valve disease is a common valvular disease with two arguably distinct phenotypes: fibroelastic deficiency and Barlow's disease. These phenotypes significantly alter the microstructures of the leaflets, particularly the collagen fibers, which are the main mechanical load carriers. The predominant method of investigation is histological sections. However, the sections are cut transmurally and provide a lateral view of the microstructure of the leaflet, while the mechanics and function are determined by the planar arrangement of the collagen fibers. This study, for the first time, quantitatively examined planar collagen distribution quantitatively in health and disease using second harmonic generation microscopy throughout the thickness of the mitral valve leaflets. Twenty diseased samples from eighteen patients and six control samples were included in this study. Healthy tissue had highly aligned collagen fibers. In fibroelastic deficiency they are less aligned and in Barlow's disease they are completely dispersed. In both diseases, collagen fibers have two preferred orientations, which, in contrast to the almost constant one orientation in healthy tissues, also vary across the thickness. The results indicate altered in vivo mechanical stresses and strains on the mitral valve leaflets as a result of disease-related collagen remodeling, which in turn triggers further remodeling., (© 2024. The Author(s).)

The presence of bright resonance of more than 1 mm or more cusps of the aortic valve, mitral valve or mitral annulus is termed as cardiac valve calcification. If an intense echo producing structure located at the junction of the atrioventricular groove and posterior mitral valve leaflet on Echocardiography that is Mitral annular calcification (MAC). This study was conducted to observe the association of MAC with clinical and echocardiographic findings of ischemic heart disease (IHD) and the role of trans-thoracic echocardiography to detect MAC which is a marker IHD. In this prospective, observational, case-control study, total of 100 IHD patients, 50 patients with MAC were assigned as case group and 50 patients without MAC were control group after fulfilling inclusion criteria. All the detailed history, clinical examination and relevant investigation reports of each patient were recorded in pre designed data collection sheet. MAC was detected with transthorasic echocardiography. Analysis was done to observe the association and correlation of MAC with clinical findings of IHD. Mean age of the case control was 55.16±10.73 years and control was 49.80±8.84 years. MAC was noted highest about 56.0% in between age 45 to 60 years. Eighty two percent (82.0%) of cases and 84.0% of controls were male, 18.0% of cases and 16.0% of controls were female. BMI among the MAC group 2.0% were underweight, 72.0% normal, 24.0% over weight and 2.0% were obese and among non MAC controls group 10.0% were underweight, 68.0% normal, 20.0% over weight and 2.0% were obese. Clinically among cases 14(28.0%) had Stable angina, 8(16.0%) had UA, 3(6.0%) had Non STEMI, 2(4.0%) had AMI, 2(4.0%) had Recent myocardial infarction and 21(42.0%) had OMI. Diabetes mellitus was significantly higher in the case groups (p=0.006). Significant p-value was noted in hyper-triyglyceridemia and low HDL in case group than control. Echocardiographic studies showed 52.0% of cases and 32.0% of controls had regional wall motion abnormality (RWMA). Transthorasic echocardiographically detected MAC is an independent predictor of Ischemic heart disease. The low cost, portable and radiation free nature of the ultrasound approach make MAC an attractive parameter in the ongoing search for IHD.

Purpose of Review: This review offers an evidence-based analysis of established and emerging cardiovascular magnetic resonance (CMR) techniques used to assess the severity of primary mitral regurgitation (MR), identify adverse cardiac remodeling and its prognostic effect. The aim is to provide different insights regarding clinical decision-making and enhance the clinical outcomes of patients with MR., Recent Findings: Cardiac remodeling and myocardial replacement fibrosis are observed frequently in the presence of substantial LV volume overload, particularly in cases with severe primary MR. CMR serves as a useful diagnostic imaging modality in assessing mitral regurgitation severity, early detection of cardiac remodeling, myocardial dysfunction, and myocardial fibrosis, enabling timely intervention before irreversible damage ensues. Incorporating myocardial remodeling in terms of left ventricular (LV) dilatation and myocardial fibrosis with quantitative MR severity assessment by CMR may assist in defining optimal timing of intervention., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: The aim of this study is to provide an update on mitral valve prolapse (MVP) and mitral annular disjunction (MAD) and who may be at risk for ventricular arrhythmias and sudden cardiac death., Recent Findings: MVP is generally considered a benign condition. However, a small subset of patients may be at risk for life-threatening ventricular arrhythmias. Among the risk factors identified in adults include patients with bileaflet mitral valves, myxomatous changes, myocardial fibrosis, and the presence of MAD. Advances in multimodal imaging have allowed for improved identification of fibrosis, anatomical valve derangements, and the amount of MAD. Recent guidelines have suggested that patients with MVP with or without MAD may be at risk for life-threatening arrhythmias if they have had prior ventricular arrhythmias, ventricular dysfunction, or unexplained syncope. Yet, extrapolation of adult data to a pediatric cohort with similar MVP and MAD at this juncture is challenging. There is, however, early evidence that some pediatric patients with significant myocardial fibrosis or abnormal tissue Doppler may be at risk for ventricular tachycardia., Summary: Mitral valve prolapse and mitral annular disjunction at times coexist and at other times can be seen as isolated entities. While the incidence of arrhythmic MVP is quite rare, there is increasing evidence that certain select adults with MVP may be at risk for ventricular tachycardia and sudden cardiac death. Future multicenter studies are needed to better understand the natural history of arrhythmic mitral valve disease and how early disease manifestation in children may impact findings now being reported in young adults., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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 Fbn1 C1039G/+ 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-β-galactosidase) reporter mice. Single-cell RNA sequencing was performed from mitral valves of wild-type and Fbn1 C1039G/+ 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; Fbn1 C1039G/+ 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 Fbn1 C1039G/+ mice. Single-cell transcriptomics revealed similar mitral valve cell heterogeneity between wild-type and Fbn1 C1039G/+ mice at 1 month of age. Wnt pathway genes were predominantly expressed in valve interstitial cells and valve endothelial cells of Fbn1 C1039G/+ mice. Inhibition of Wnt signaling in Fbn1 C1039G/+ 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., Competing Interests: Disclosures None.

Objective: To characterize myxomatous mitral valve disease (MMVD) in Labrador Retrievers (LRs) and Golden Retrievers (GRs)., Methods: 52 LRs and 20 GRs diagnosed with MMVD composed a retrospective study sample (February 1, 2010, to July 31, 2021). Stored echocardiograms were remeasured. Dogs were staged by 2019 MMVD consensus guidelines., Results: Mean age was 9.9 years in LRs and 9.5 years in GRs, with 31 of 52 LRs (59.6%) and 13 of 20 (65.0%) GRs being male. Forty-six LRs were stage B1 (88.5%), 3 were B2 (5.8%), and 3 were C (5.8%). Fourteen GRs were stage B1 (70.0%), 2 were B2 (10.0%), and 4 were C (20.0%). Of LRs and GRs in stage B2/C, 50% had systolic dysfunction. Atrial fibrillation (AF) and ventricular arrhythmias were identified in 2 of 52 (3.8%) and 10 of 52 (19.2%) LRs at initial diagnosis versus 3 of 20 (15.0%) and 3 of 20 (15.0%) GRs, respectively. All 5 AF dogs were stage C, with intermediate to high probability of pulmonary hypertension. Two additional GRs developed AF during follow-up; thus 5 of 6 (83.3%) stage B2/C GRs ultimately experienced AF. Subjective mitral valve thickening was frequent in both breeds (41/52 LRs [78.8%]; 18/20 GRs [90.0%]), while mitral valve prolapse was more common in LRs (22/52 [42.3%]) than GRs (5/20 [25.0%])., Conclusions: In LRs and GRs, MMVD was relatively late onset, with males overrepresented. Both breeds exhibited mitral valve thickening in association with MMVD, while LRs more commonly exhibited mitral valve prolapse., Clinical Relevance: While most LRs and GRs with MMVD were stage B1, those in stage B2/C had increased prevalence of systolic dysfunction and AF.

Forensic pathologists often encounter cases of acute subdural hematoma (SDH) due to trauma, whereas those attributable to endogenous causes are rare. Here, we report a case of the latter type in a 42-year-old man who was found dead at home after several months of fever and malaise. Postmortem computed tomography (PMCT) and autopsy were undertaken to clarify the cause of death. PMCT images revealed a fatal SDH and a localized hyper-density area in the right parietal lobe; macroscopic and microscopic examinations revealed SDH due to rupture of a mycotic aneurysm (MA) associated with meningitis. The PMCT images also indicated thickening and calcification of the mitral valve, while autopsy demonstrated infective endocarditis (IE). In addition, PMCT demonstrated a low-density area in the spleen, which was shown to be a splenic abscess at autopsy. PMCT also demonstrated tooth cavities. Based on the findings of autopsy, the cause of death was considered to be SDH due to rupture of the MA resulting from meningitis with IE and splenic abscess. Although PMCT was unable to clarify the significance of any individual feature, a retrospective review of the PMCT images might have suggested IE, bacteremia, or ruptured MA leading to SDH. This case suggests that, instead of interpreting individual features demonstrated on PMCT images, integrated interpretation of overall PMCT findings might provide clues for identifying causes of death, despite the fact that PMCT lacks diagnostic accuracy for infectious diseases such as IE and meningitis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Intracardiac cysts are quite rare cardiac pathology in the adults. In this paper we describe a clinical observation for a mitral valve cyst in a male patient, 31 year. This patient had complaints on complicated swallowing, dizziness, nausea, episodes of consciousness loss and was indicated to have transthoracic echocardiography. During the echocardiographic research on a anterior leaf of the mitral valve we found a cavitary lesion with the size 27 x 38 mm which did not interfere with the blood supply in an output path of the left ventricle. The patient was successfully operated. Histologic research showed a true cyst of the mitral valve.

Myxomatous mitral valve disease (MMVD) is the most common cardiovascular disorder in dogs with a high prevalence, accounting for approximately 75% of all canine heart disease cases. MMVD is a complex disease and shows variable progression from mild valve leakage to severe regurgitation, potentially leading to heart failure. However, the molecular mechanisms and age-related changes that govern disease progression, especially at the early stage (B1) before the development of discernable clinical signs, remain poorly understood. In this prospective study, we aimed to compare gene expression differences between blood samples of aged beagle dogs with stage B1 MMVD and those of healthy controls using RNA sequencing. Clinical evaluation was also conducted, which revealed minimal differences in radiographic and echocardiographic measurements despite distinct biomarker variations between the two groups. Comparative transcriptomics revealed differentially expressed genes associated with extracellular matrix remodeling, prostaglandin metabolism, immune modulation, and interferon-related pathways, which bear functional relevance for MMVD. In particular, the top 10 over- and under-expressed genes represent promising candidates for influencing pathogenic changes in MMVD stage B1. Our research findings, which include identified variations in clinical markers and gene expression, enhance our understanding of MMVD. Furthermore, they underscore the need for further research into early diagnosis and treatment strategies, as, to the best of our knowledge, no prior studies have explored the precise molecular mechanisms of stage B1 in MMVD through total RNA sequencing., Competing Interests: The authors have declared no conflicts of interest in relation to the research, authorship or publication of this article, (Copyright: © 2024 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mitral annular calcification (MAC) is a chronic and degenerative condition involving calcification of the mitral annulus. MAC is a risk factor for coronary artery disease, cardiovascular events, stroke, and cardiovascular death. However, patients with MAC are often asymptomatic. Herein, we present the first case of cardiac tamponade due to infection of MAC in forensic pathology. An 80-year-old woman was found in cardiopulmonary arrest shortly after experiencing fatigue. She was transferred to a hospital, and despite chest compression and ventilation, she was pronounced dead due to no response. Postmortem computed tomography, autopsy, and histological examination showed MAC, abscess formation involving Gram-positive cocci on the MAC, and fistulation of the abscess into the intracardial pericardial cavities, resulting in a massive lethal hemopericardium., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: Mitral valve prolapse (MVP) is an accepted cause of sudden cardiac death (SCD) in most autopsy series. Diagnosis at autopsy relies upon subjective assessment with no established objective pathological criteria. This study set out to establish objective measurements to help pathologists dealing with SCD., Methods: We diagnosed 120 (1.5%) cases of MVP in 8108 cases of SCD. We measured the mitral annulus, anterior and posterior leaflets, rough zone and mitral annular disjunction (MAD) in 27 MVP cases and compared them to 54 age- and sex-matched normal mitral valves., Results: Age of death was 39 ± 16 years, with 59 females and 61 males. History of mild MV disease was present in 19 (16%). Eleven (9%) died associated with exertion. Left ventricular hypertrophy was present in nine (15%) females and 10 (16%) males. Both MV leaflets showed thickening and ballooning in all individuals. MVP showed highly significantly increased annular circumference, elongation and thickening of both leaflets as well as increased MAD (all P < 0.001). Left ventricular fibrosis was present in 108 (90%), with interstitial fibrosis in the posterolateral wall and papillary muscle in 88 (81%) and coexisting replacement fibrosis in 40 (37%)., Conclusion: This is the largest MVP associated with SCD series highlighting a young cohort with equal representation of males and females. There is involvement of both leaflets with significant annular dilatation, elongation and thickening of both leaflets with MAD. Left ventricular fibrosis explains arrhythmia. Our quantitative measurements should serve as a reference for pathologists assessing post-mortem hearts for MVP., (© 2024 The Authors. Histopathology published by John Wiley & Sons Ltd.)

There is a broad spectrum of mitral valve diseases ranging from young patients with rheumatic mitral valve stenosis up to older patients with secondary mitral valve regurgitation and numerous comorbidities. A profound understanding of the etiology, anatomical characteristics of mitral valve diseases and current treatment options is necessary to be able to prepare a patient-centered treatment approach. The interdisciplinary collaboration of referring physicians, interventional cardiologists, cardiac surgeons, heart failure and imaging specialists as well as anesthesiologists is a cornerstone of optimal patient treatment., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Shone's complex is a congenital cardiac disease consisting of the following four lesions: parachute mitral valve, supravalvar mitral ring, subaortic stenosis, and aortic coarctation. Though not all components are required for a diagnosis, the end result is both left ventricular inflow and outflow obstruction, which typically present in patients as congestive heart failure. The complex pathology requires careful management and surgical decision-making to ensure an optimal outcome. This review will focus on the anatomy, physiology, and perioperative anesthetic management of patients with Shone's complex., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The mitral valve disease (MVD) in Lutembacher's syndrome has been infrequently analyzed from a pathological standpoint. In this study, we have attempted to elucidate the pathology of MVD in this interesting syndrome in 44 autopsied cases of combined non-primum atrial septal defect (ASD) and MVD collected over 16 years. The patients were divided into 3 groups: Group 1: non-primum ASD with clinically diagnosed mitral stenosis (MS) ± regurgitation, Group 2: non-primum ASD with clinically diagnosed mitral regurgitation (MR) and, Group 3: non-primum ASD with no clinically evident MVD, but with mitral valve pathology diagnosed at autopsy. All 44 patients were symptomatic. There were 26 males (59%). The ages ranged from 13 to 73 years. A history of rheumatic fever was available in 2 patients while 16 patients had undergone surgery or intervention for the disease. Of the 18 patients in Group 1, six patients did not show histological features of rheumatic heart disease, although they shared similar gross morphological features. Furthermore, the mitral regurgitation in 12 of 19 patients in Group 2 was non-rheumatic. Also, only one patient had histological evidence of rheumatic activity among seven cases in Group 3. In spite of a high rheumatic load at our center, more than half (54.5%) of patients had “non-rheumatic” mitral valve pathology. Thus, the mitral valvular lesions commonly labeled ‘rheumatic’ in Lutembacher's syndrome are not always so. The distinction into rheumatic and non-rheumatic MVD in non-primum ASD has to be made on the basis of microscopic criteria.

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Cardiac papillary fibroelastoma is a rare benign tumor, which is often mistaken for a vegetation. Predominantly asymptomatic, it can cause life-threatening complications. Although rare, mobile papillary fibroelastoma movement between affected valves may hamper valve closure and damage the valve, leading to valvular regurgitation. Endothelial damage increases the risk of developing infective endocarditis. We report a rare case of a highly mobile papillary fibroelastoma originating from the atrial septum touching the mitral valve, leading to mitral regurgitation and, eventually, infective endocarditis., Case Presentation: A 26-year-old woman with suspected infective endocarditis was referred to us from a previous hospital after having experienced intermittent fever for a month. Before the fever, she had been experiencing exertional dyspnea. In addition, she had undergone a cesarean section two weeks before this admission. A transthoracic echocardiogram showed a mobile mass originating from the atrial septum touching the mitral valve with severe mitral regurgitation. Computed tomography revealed an occluded right profunda femoris artery with an embolus. Infective endocarditis associated with a mobile vegetation with high embolic risk was diagnosed, and urgent surgery was performed. Following the surgery, examinations revealed papillary fibroelastoma originating from the atrial septum and infective endocarditis of the mitral valve. The histopathological examination confirmed that a mass initially thought to be a mobile vegetation was a papillary fibroelastoma. The postoperative course was uneventful except for pericarditis. There has been no recurrence of infective endocarditis or papillary fibroelastoma., Conclusions: The highly mobile papillary fibroelastoma was thought to have caused both chronic mitral regurgitation and infective endocarditis. Mobile papillary fibroelastomas can cause endothelial damage to nearby valves and predispose patients to infective endocarditis., (© 2024. The Author(s).)

Objective: Mouse models of Marfan syndrome (MFS) with Fibrillin 1 (Fbn1) variant C1041G exhibit cardiovascular abnormalities, including myxomatous valve disease (MVD) and aortic aneurism, with structural extracellular matrix (ECM) dysregulation. In this study, we examine the structure-function-mechanics relations of the mitral valve related to specific transitions in ECM composition and organization in progressive MVD in MFS mice from Postnatal day (P)7 to 1 year-of-age., Approach and Results: Mechanistic links between mechanical forces and biological changes in MVD progression were examined in Fbn1 C1041G/+  MFS mice. By echocardiography, mitral valve dysfunction is prevalent at 2 months with a decrease in cardiac function at 6 months, followed by a preserved cardiac function at 12 months. Mitral valve (MV) regurgitation occurs in a subset of mice at 2-6 months, while progressive dilatation of the aorta occurs from 2 to 12 months. Mitral valve tissue mechanical assessments using a uniaxial Permeabilizable Fiber System demonstrate decreased stiffness of MFS MVs at all stages. Histological and microscopic analysis of ECM content, structure, and fiber orientation demonstrate that alterations in ECM mechanics, composition, and organization precede functional abnormalities in Fbn1 C1041G/+ MFS MVs. At 2 months, ECM abnormalities are detected with an increase in proteoglycans and decreased stiffness of the mitral valve. By 6-12 months, collagen fiber remodeling is increased with abnormal fiber organization in MFS mitral valve leaflets. At the same time, matrifibrocyte gene expression characteristic of collagen-rich connective tissue is increased, as detected by RNA in situ hybridization and qPCR. Together, these studies demonstrate early prevalence of proteoglycans at 2 months followed by upregulation of collagen structure and organization with age in MVs of MFS mice., Conclusions: Altogether, our data indicate dynamic regulation of mitral valve structure, tissue mechanics, and function that reflect changes in ECM composition, organization, and gene expression in progressive MVD. Notably, increased collagen fiber organization and orientation, potentially dependent on increased matrifibrocyte cell activity, is apparent with altered mitral valve mechanics and function in aging MFS mice., (Copyright © 2024. Published by Elsevier B.V.)

Nonbacterial thrombotic endocarditis (NBTE) is a manifestation of prothrombotic status observed in patients with malignancy. Most cases are discovered only in the advanced stages. However, cancer in early stages may also induce NBTE development. We herein report an 87-year-old man with NBTE with multiple thromboembolization coexisting with lung cancer in early clinical stage. Autopsy findings revealed platelet- and fibrin-rich vegetations in both the tricuspid and mitral valves without evidence of bacterial infection. NBTE should be considered in cases with occult thromboembolization. Not only the presence of typical vegetation but irregular leaflet thickening should be monitored with careful echocardiographic examinations.

Prosthetic valve obstruction is a rare but potentially lethal complication. The most frequent causes are thrombus and pannus formation, in the absence of infectious data. Diagnosis is not always easy using cardiac CT scanning and in 46%-85% of cases thrombus and pannus coexist, complicating the diagnosis. A rapid diagnosis is essential to avoid a fatal outcome of this pathology whose mortality, despite correct treatment, is high., (Copyright © 2023 SERAM. Published by Elsevier España, S.L.U. All rights reserved.)

Aims: Anterior mitral valve leaflet (AMVL) elongation is detectable in overt and subclinical hypertrophic cardiomyopathy (HCM). We sought to investigate the dynamic motion of the aorto-mitral apparatus to understand the behaviour of the AMVL and the mechanisms of left ventricular outflow tract obstruction (LVOTO) predisposition in HCM., Methods and Results: Cardiovascular magnetic resonance imaging using a 1.5 Tesla scanner was performed on 36 HCM sarcomere gene mutation carriers without left ventricular hypertrophy (G+LVH-), 31 HCM patients with preserved ejection fraction carrying a pathogenic sarcomere gene mutation (G+LVH+), and 53 age-, sex-, and body surface area-matched healthy volunteers. Dynamic excursion of the aorto-mitral apparatus was assessed semi-automatically on breath-held three-chamber cine steady-state free precession images. Four pre-defined regions of interest (ROIs) were tracked: ROIPMVL: hinge point of the posterior mitral valve leaflet; ROITRIG: intertrigonal mitral annulus; ROIAMVL: AMVL tip; and ROIAAO: anterior aortic annulus. Compared with controls, normalized two-dimensional displacement-vs.-time plots in G+LVH- revealed subtle but significant systolic anterior motion (SAM) of the AMVL (P < 0.0001) and reduced longitudinal excursion of ROIAAO (P = 0.014) and ROIPMVL (P = 0.048). In overt and subclinical HCM, excursion of the ROITRIG/AMVL/PMVL was positively associated with the burden of left ventricular fibrosis (P < 0.028). As expected, SAM was observed in G+LVH+ together with reduced longitudinal excursion of ROITRIG (P = 0.049) and ROIAAO (P = 0.008)., Conclusion: Dyskinesia of the aorto-mitral apparatus, including SAM of the elongated AMVL, is detectable in subclinical HCM before the development of LVH or left atrial enlargement. These data have the potential to improve our understanding of early phenotype development and LVOTO predisposition in HCM., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Peripheral blood carries a reservoir of mRNAs that regulate cardiac structure and function potential. Although it is well recognized that the typical symptoms of Myxomatous Mitral Valve Disease (MMVD) stage B2 are long-standing hemodynamic disorder and cardiac structure remodeling caused by mitral regurgitation, the transcriptomic alterations in blood from such dogs are not understood., Results: In the present study, comparative high-throughput transcriptomic profiling of blood was performed from normal control (NC) and naturally-occurring MMVD stage B2 (MMVD) dogs. Using Weighted Gene Co-expression Network Analyses (WGCNA), Gene Ontology (GO), and Kyoto Encyclopedia of Gene and Genomes (KEGG), we identified that the turquoise module was the most highly correlated with echocardiographic features and found 64 differentially expressed genes (DEGs) that were significantly enriched in platelet activation related pathways. Therefore, from the turquoise module, we selected five DEGs (MDM2, ROCK1, RIPK1, SNAP23, and ARHGAP35) that, according to real-time qPCR, exhibited significant enrichment in platelet activation related pathways for validation. The results showed that the blood transcriptional abundance of MDM2, ROCK1, RIPK1, and SNAP23 differed significantly (P < 0.01) between NC and MMVD dogs. On the other hand, Correlation Analysis revealed that MDM2, ROCK1, RIPK1, and SNAP23 genes negatively regulated the heart structure parameters, and followed the same trend as observed in WGCNA., Conclusion: We screened four platelet activation related genes, MDM2, ROCK1, RIPK1, and SNAP23, which may be considered as the candidate biomarkers for the diagnosis of MMVD stage B2. These findings provided new insights into MMVD pathogenesis., (© 2023. The Author(s).)

This study evaluates operative approach and contemporary surgical outcomes in the management of left ventricular outflow tract obstruction by a single surgeon at a high-volume, specialized hypertrophic cardiomyopathy center. This is a retrospective review of 1559 consecutive operations for left ventricular outflow tract obstruction from 2005 to 2015. Demographic profiles, echocardiogram-derived ventricular morphology and hemodynamics, operative data, and in-hospital outcomes were analyzed. Of the 1559 operations, 586 were isolated septal myectomies, 522 were myectomies with mitral valve or subvalvular apparatus intervention, 422 were myectomies with another concomitant procedure, and 29 were isolated mitral valve interventions without myectomy. Common mitral valve interventions included anterior leaflet shortening (16%), chordae tendineae resection (9.8%), papillary muscle resection (7.2%), and papillary muscle reorientation (7.5%). Ninety-two patients underwent mitral valve replacement, 42 for left ventricular outflow tract obstruction and 50 for intrinsic mitral valve pathology. Patients undergoing mitral interventions had thinner septums (18 ± 0.4 mm vs 22 ± 0.5 mm, P <.001) and less myocardium removed (6.2 ± 3.5 g vs 8.8 ± 3.8 g, P <.001) than patients without a mitral intervention. Prevalence of in-hospital permanent pacemaker insertion was 4.2% (n = 1334) for complete heart block and 1.1% (n = 464) for isolated septal myectomy with normal preoperative conduction. Overall, there were 2 postoperative ventricular septal defects (0.13%) and none for isolated myectomies. Operative mortality was 0.38%. Septal myectomy can be performed safely with excellent outcomes when the procedure is performed by a highly experienced surgeon in a high-volume, specialized center. A mitral valve intervention is a useful adjunct in patients with moderate hypertrophy. [ABSTRACT FROM AUTHOR]

The 2021 International Paediatric and Congenital Cardiac Code and the Eleventh Revision of the International Classification of Diseases provide the following definition for hypoplastic left heart syndrome (HLHS): "Hypoplastic left heart syndrome (HLHS) is defined as a spectrum of congenital cardiovascular malformations with normally aligned great arteries without a common atrioventricular junction, characterized by underdevelopment of the left heart with significant hypoplasia of the left ventricle including atresia, stenosis, or hypoplasia of the aortic or mitral valve, or both valves, and hypoplasia of the ascending aorta and aortic arch." Although HLHS with intact ventricular septum (HLHS + IVS) and HLHS with ventricular septal defect (HLHS + VSD) are different cardiac phenotypes, both of these lesions are part of the spectrum of HLHS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Acute severe mitral regurgitation (MR) is rare, but often leads to cardiogenic shock, pulmonary edema, or both. Most common causes of acute severe MR are chordae tendineae (CT) rupture, papillary muscle (PM) rupture, and infective endocarditis (IE). Mild to moderate MR is often seen in patients with acute myocardial infarction (AMI). CT rupture in patients with floppy mitral valve/mitral valve prolapse is the most common etiology of acute severe MR today. In IE, native or prosthetic valve damage can occur (leaflet perforation, ring detachment, other), as well as CT or PM rupture. Since the introduction of percutaneous revascularization in AMI, the incidence of PM rupture has substantially declined. In acute severe MR, the hemodynamic effects of the large regurgitant volume into the left atrium (LA) during left ventricular (LV) systole, and in turn back into the LV during diastole, are profound as the LV and LA have not had time to adapt to this additional volume. A rapid, but comprehensive evaluation of the patient with acute severe MR is essential in order to define the underline cause and apply appropriate management. Echocardiography with Doppler provides vital information related to the underlying pathology. Coronary arteriography should be performed in patients with an AMI to define coronary anatomy and need for revascularization. In acute severe MR, medical therapy should be used to stabilize the patient before intervention (surgery, transcatheter); mechanical support is often required. Diagnostic and therapeutic steps should be individualized, and a multi-disciplinary team approach should be utilized., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We report a case of a 73-year-old male with rheumatoid arthritis presenting with acute abdominal and back pain and rapidly developing multiorgan failure. A positive blood culture (Staphylococcus aureus, Candida species) followed by transoesophageal sonography established a diagnosis of mitral valve infective endocarditis. At the autopsy, the heart examination revealed fibrinous pericarditis and multiple small vegetations on the mitral valve. The mitral valve itself showed no significant damage. Surprisingly, the histological examination of the mitral valve showed granulomatous inflammation with central fibrinoid necrosis and peripheral palisade of histiocytes, with occasional giant cells and lymphocytic inflammatory infiltrate - findings consistent with a rheumatoid nodule. Infective vegetations were overlying the nodule. Due to its relative frequency, a possibility of cardiac involvement by rheumatoid arthritis and its potential infective complications should be considered in patients with appropriate history and clinical symptoms.

Hypertrophic cardiomyopathy (HCM) is an inherited myocardial disease at risk of sudden cardiac death and heart failure, even requiring heart transplantation. A "muscular mitral-aortic discontinuity" has been reported during surgery in the obstructive form. We aimed to validate these findings through pathological analysis of HCM heart specimens from the cardiovascular pathology tissue registry. Hearts with septal asymmetric HCM from sudden cardiac death, other causes of death, or heart transplantation were included. Sex-matched and age-matched patients without HCM served as controls. Gross and histologic analysis of the mitral valve (MV) apparatus and the mitral-aortic continuity were performed. Thirty HCM hearts (median age, 29.5 years; 15 men) and 30 controls (median age, 30.5 years; 15 men) were studied. In HCM hearts, a septal bulging was present in 80%, an endocardial fibrous plaque in 63%, a thickening of the anterior MV leaflet in 56.7%, and an anomalous insertion of papillary muscle in 10%. All cases but 1 (97%) revealed a myocardial layer overlapping the mitral-aortic fibrous continuity on the posterior side, corresponding to the left atrial myocardium. A negative correlation between the length of this myocardial layer and the age and the anterior MV leaflet length was found. The length did not differ between HCM and controls. Pathologic study of obstructive HCM hearts does not confirm the existence of a "muscular mitral-aortic discontinuity". An extension of left atrial myocardium, overlapping posteriorly the intervalvular fibrosa, is rather visible, and its length decreases with age, possibly as a consequence of left atrial remodeling. Our study highlights the fundamental role of thorough gross examination and the value of organ retention for further analysis in order to validate new surgical and imaging findings., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Whilst abnormally increased left ventricular wall thickness is the hallmark feature of hypertrophic cardiomyopathy (HCM), anomalies of the mitral valve and supporting apparatus are well documented. This review addresses the clinical importance of mitral valve abnormalities in HCM, their mechanistic associations with symptoms, and therapeutic strategies targeting mitral valve and apparatus abnormalities., Recent Findings: The normal mitral valve possesses anatomical features facilitating unrestricted blood flow during LV filling, preventing regurgitation during LV systole, and avoiding obstruction of LV ejection. In HCM, a variety of structural and functional abnormalities can conspire to cause deranged mitral valve function, with implications for management strategy. Identification and characterization of these abnormalities is facilitated by multimodality imaging. Alcohol septal ablation (ASA) cannot address primary mitral valve abnormalities, and so is not preferred to surgical intervention if mitral valve abnormalities are present and are judged to make dominant contributions to LV outflow tract obstruction (LVOTO). Two broadly opposing surgical intervention strategies exist, one advocating isolated septal myectomy and the other including adjuvant mitral apparatus modification. Newer, less invasive surgical and transcatheter techniques will expand interventional options., Summary: Mitral valve abnormalities are a central pathological feature of HCM. Multimodality imaging is crucial for their identification and characterization prior to therapeutic intervention., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The authors report a case of a patient with a history of immunoglobulin A nephropathy who, during the admission for pneumonia, had an incidental finding of a huge mitral valve (MV) mass on transthoracic echocardiography. The differential diagnosis was challenging because the clinical scenario raised the suspicion of possible infective endocarditis, and the imaging features were suggestive of a myxoma or vegetation. The patient underwent urgent excision of the mass with MV replacement due to the high risk of embolism. Intraoperative findings were consistent with clots or vegetation. The pathology result of the thrombus was beyond our imagination, and to the best of our knowledge, only one case has been reported. Awareness about native MV thrombosis and its etiologic factors, work-up, and management is key for better medical and surgical management planning because this condition is extremely rare and challenging in the clinical and imaging arenas.

Native cardiac valves in the setting of chronic injury may become thickened and disrupted by dystrophic calcification, which impede valve structure/function, and there may be evidence of chondromatous (i.e., cartilaginous, CM) metaplasia admixed with dystrophic calcification. In order to characterize the presence of CM in native cardiac valves - with particular focus upon aortic valves - a retrospective review of the histologic features of 46 native aortic valves (identified from 1094 sequentially reviewed native valves of all types) containing CM were focused upon, as well as correlation with other histopathologic features, and clinical and echocardiographic findings. The prevalence rate of CM was low, and greatest among aortic valves, less in mitral valves, and never identified in tricuspid or pulmonic valves. CM in aortic valves was less commonly identified in patients with a history of autoimmune disease. The rate of CM increased with degree of valve thickening and/or calcification. The proportion of aortic valves with CM increased with an increasing degree of stenosis and decreasing degree of regurgitation, and aortic valves with CM were more commonly associated with a smaller aortic valve area, and greater peak and mean gradients. The rate of osseous metaplasia, arterial vessels, capillary bed formation, and chronic inflammation were greater in aortic valves with CM compared to valves without. CM within aortic valves is an infrequent albeit identifiable histopathologic alteration associated with chronic valve disease alongside changes in valve thickening and calcification., (© 2023 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Rheumatic heart disease (RHD) is an autoimmune sequel of pharyngitis and rheumatic fever that leads to permanent heart valve damage, especially the mitral valves. The mitral valves, which are responsible for the binding of auto-antibodies during immune response generation, lead to valve scarring and eventually valves dysfunction. Recently, exosomes (EXOs), the nano-sized vesicles, which range in size from 30 to 150 nm, are reported in various cardiovascular physiological and pathological processes. These vesicles are found in several body fluids such as plasma, serum, and also in cell culture media. Exosomal cargo contains proteins, which are taken up by the recipient cells and modulate the cellular characteristics. The role of exosomal proteins in RHD is still obscure. Hence, the present study has been designed to unveil the exosomal proteins in disease severity during RHD. In this study, the exosomes were isolated from biological fluids (serum and pericardial fluid) of RHD patients as well as from their respective controls. Protein profiling of these isolated exosomes revealed that alpha-1 antitrypsin is up-regulated in the biological fluids of RHD patients. The enhanced levels of exosomal alpha-1 antitrypsin, were further, validated in biological samples and mitral valve tissues of RHD patients, to correlate with the disease severity. These findings suggest an association of increased levels of exosomal alpha-1 antitrypsin with the RHD pathogenesis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

PI3K/AKT/mTOR signalling contributes to several cardiovascular disorders. The aim of this study was to examine the PI3K/AKT/mTOR pathway in myxomatous mitral valve disease (MMVD). Double-immunofluorescence examined expression of PI3K and TGF-β1 in canine valves. Valve interstitial cells (VICs) from healthy or MMVD dogs were isolated and characterized. Healthy quiescent VICs (qVICs) were treated with TGF-β1 and SC-79 to induce activated myofibroblast phenotypes (aVICs). Diseased valve-derived aVICs were treated with PI3K antagonists and expression of RPS6KB1 (encoding p70 S6K) was modulated using siRNA and gene overexpression. SA-β-gal and TUNEL staining were used to identify cell senescence and apoptosis, and qPCR and ELISA to examine for senescence-associated secretory phenotype. Protein immunoblotting was used to examine expression of phosphorylated and total proteins. TGF-β1 and PI3K are highly expressed in mitral valve tissues. Activation of PI3K/AKT/mTOR and increased expression of TGF-β are found in aVICs. TGF-β transitions qVICs to aVICs by upregulation of PI3K/AKT/mTOR. Antagonism of PI3K/AKT/mTOR reverses aVIC myofibroblast transition by inhibiting senescence and promoting autophagy. Upregulation of mTOR/S6K induces transformation of senescent aVICs, with reduced capacity for apoptosis and autophagy. Selective knockdown of p70 S6K reverses cell transition by attenuating cell senescence, inhibiting apoptosis and improving autophagy. TGF-β-induced PI3K/AKT/mTOR signalling contributes to MMVD pathogenesis and plays crucial roles in the regulation of myofibroblast differentiation, apoptosis, autophagy and senescence in MMVD., (© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Aims: The role of lipoprotein(a) [Lp(a)] as a possibly causal risk factor for atherosclerotic artery disease and aortic valve stenosis has been well established. However, the information available on the association between Lp(a) levels and mitral valve disease is limited and controversial. The main objective of the present study was to assess the association between Lp(a) levels and mitral valve disease., Data Synthesis: This systematic review was performed according to PRISMA guidelines (PROSPERO CRD42022379044). A literature search was performed to detect studies that evaluated the association between Lp(a) levels or single-nucleotide polymorphisms (SNPs) related to high levels of Lp(a) and mitral valve disease, including mitral valve calcification and valve dysfunction. Eight studies including 1,011,520 individuals were considered eligible for this research. The studies that evaluated the association between Lp(a) levels and prevalent mitral valve calcification found predominantly positive results. Similar findings were reported in two studies that evaluated the SNPs related to high levels of Lp(a). Only two studies evaluated the association of Lp(a) and mitral valve dysfunction, showing contradictory results., Conclusions: This research showed disparate results regarding the association between Lp(a) levels and mitral valve disease. The association between Lp(a) levels and mitral valve calcification seems more robust and is in line with the findings already demonstrated in aortic valve disease. New studies should be developed to clarify this topic., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: None declared.