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Mitral Valve Development and Disease

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A special issue of Journal of Cardiovascular Development and Disease (ISSN 2308-3425).

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 56161

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Special Issue Editors

Dr. Nina Ajmone Marsan

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Guest Editor

Department of Cardiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherland
Interests: mitral valve prolapse; mitral regurgitation; aortic stenosis; cardiovascular imaging
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Russell Norris

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Guest Editor

Department of Regenerative Medicine and Cell Biology, Cardiovascular Developmental Biology Center, Children's Research Institute, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA
Interests: cardiac development; valve development; cardiovascular genetics; valve diseases; mitral valve prolapse; calcific aortic stenosis; ischemic MR; HOCM; myxomatous valves; fibroblast- myocyte interactions; fibrosis; primary cilia; cytoskeleton; membrane receptors; transcription factors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Mitral valve disease, the focus of this Special Issue, is one of the most common forms of cardiac valve disease and affects ~2%–3% of the human population. As such, mitral valve defects carry a significant burden of morbidity and mortality and can lead to secondary complications such as arrhythmias, heart failure, and sudden cardiac death. Mitral valve surgery is currently the only therapeutic option for these patients, and is the fastest-growing cardiovascular intervention in the Western world. There are no effective nonsurgical treatments for this group of diseases, and therapeutic efforts have been hindered by an incomplete understanding of their fundamental causes. In recent years, our understanding of the genetic and molecular basis of heart valve diseases has significantly improved. New genetic discoveries have informed true causes of mitral valve disease in the human population. For the most part, cell lineages that contribute to the development of the mitral valve leaflets have been uncovered. However, the way in which these different cell lineages integrate to establish stratified valve tissues is less well understood. More importantly, research on how cellular, molecular, genetic, and epigenetic interactions interface with biomechanical cues to drive normal valve development remains in its infancy. Uncovering how defects in these various intrinsic and extrinsic factors can lead to valvular heart diseases is critical in understanding the pathophysiology of disease. Part and parcel with understanding the etiology of mitral valve disease is an appreciation of whether this understanding can impact clinical management and eventually lead to the development of new medical treatments. New research has suggested that a prolapsing mitral valve can have profound effects on extra-valvular cardiac tissues such as the annulus and left ventricular wall. Establishing mechanisms underlying secondary defects related to mitral valve disease may help inform new clinical management for this disease, with the opportunity of modifying current surgical and imaging guidelines. Similarly, how valve adaptations occur either in the context of new surgical approaches or in other cardiac conditions such as hypertrophic obstructive cardiomyopathies, endocarditis, and rheumatic and ischemic mitral regurgitation will fit logically within the framework of this Special Issue. A goal of this Issue is to stimulate new investigations into primary and secondary mitral valve defects and their relationship to pathological and clinical implications. We invite you to consider contributing a research paper or review article on any aspect related to the topic of this Special Issue. This may be also an opportunity for surgeons, cardiologists, cardiac imagers, clinical fellows, and doctoral and post-doctoral trainees to contribute to a review article and showcase their area of expertise.

Dr. Nina Ajmone Marsan
Dr. Russell Norris
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Cardiovascular Development and Disease is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

Mitral valve disease
Mitral valve development
Myxomatous valves
Primary mitral regurgitation
Secondary mitral regurgitation
Mitral valve stenosis

Published Papers (14 papers)

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Research

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11 pages, 4704 KiB

Open AccessArticle

Head to Head Comparison between Different 3-Dimensional Echocardiographic Rendering Tools in the Imaging of Percutaneous Edge-to-Edge Mitral Valve Repair

by Gloria Tamborini, Valentina Mantegazza, Anna Garlaschè, Manuela Muratori, Laura Fusini, Sarah Ghulam Ali, Claudia Cefalù, Gianpiero Italiano, Paola Gripari, Anna Maltagliati, Marco Penso and Mauro Pepi

J. Cardiovasc. Dev. Dis. 2021, 8(7), 73; https://doi.org/10.3390/jcdd8070073 - 24 Jun 2021

Cited by 7 | Viewed by 2332

Abstract

MitraClip (MC) is the most common percutaneous treatment for severe mitral regurgitation (MR). An accurate two-dimensional and three-dimensional echocardiographic (3DTEE) imaging is mandatory for the optimal procedural result. Recently transillumination 3DTEE rendering (3DTr) has been introduced integrating a virtual light source into the dataset and with the addition of glass effect (3DGl) allows to adjust tissue transparency improving depth perception and anatomical structure delineation in comparison with the standard 3DTEE (3DSt). The aim of this retrospective study in 30 patients undergoing MC, was to compare 3DSt, 3DTr, and 3DGl in mitral valve (MV) evaluation and procedural result assessment. 3DTEE acquisitions obtained before and after MC were processed with 3DSt, 3DTr, and 3DGl rendering. Each reconstruction was scored for quality and for ability to recognize MV anatomy, MR origin, clip position, dimension and grasping. Imaging quality was judged good or optimal in 52%, 76%, and 96% in 3DSt, 3DTr, and 3DGl reconstructions respectively. In 26/30 patients a diagnostic incremental value was found with 3DTr vs. 3DSt and in 15/26 with 3DGl vs. 3DTr and 3DSt. Only 3DGl with perpendicular cropping of the clip allowed to visualize and measure the grasped portion of each mitral leaflets. 3DTEE imaging during MC may be improved by 3DTr and 3DGl providing a better evaluation of MV, of leaflet grasping and of residual MR jets after MC. Full article

(This article belongs to the Special Issue Mitral Valve Development and Disease)

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14 pages, 13472 KiB

Open AccessArticle

PDGFRα: Expression and Function during Mitral Valve Morphogenesis

by Kelsey Moore, Diana Fulmer, Lilong Guo, Natalie Koren, Janiece Glover, Reece Moore, Cortney Gensemer, Tyler Beck, Jordan Morningstar, Rebecca Stairley and Russell A. Norris

J. Cardiovasc. Dev. Dis. 2021, 8(3), 28; https://doi.org/10.3390/jcdd8030028 - 13 Mar 2021

Cited by 6 | Viewed by 3201

Abstract

Mitral valve prolapse (MVP) is a common form of valve disease and can lead to serious secondary complications. The recent identification of MVP causal mutations in primary cilia-related genes has prompted the investigation of cilia-mediated mechanisms of disease inception. Here, we investigate the role of platelet-derived growth factor receptor-alpha (PDGFRα), a receptor known to be present on the primary cilium, during valve development using genetically modified mice, biochemical assays, and high-resolution microscopy. While PDGFRα is expressed throughout the ciliated valve interstitium early in development, its expression becomes restricted on the valve endocardium by birth and through adulthood. Conditional ablation of Pdgfra with Nfatc1-enhancer Cre led to significantly enlarged and hypercellular anterior leaflets with disrupted endothelial adhesions, activated ERK1/2, and a dysregulated extracellular matrix. In vitro culture experiments confirmed a role in suppressing ERK1/2 activation while promoting AKT phosphorylation. These data suggest that PDGFRα functions to suppress mesenchymal transformation and disease phenotypes by stabilizing the valve endocardium through an AKT/ERK pathway. Full article

(This article belongs to the Special Issue Mitral Valve Development and Disease)

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15 pages, 5668 KiB

Open AccessEditor’s ChoiceArticle

Myocardial TGFβ2 Is Required for Atrioventricular Cushion Remodeling and Myocardial Development

by Aniket Bhattacharya, Nadia Al-Sammarraie, Mengistu G. Gebere, John Johnson, John F. Eberth and Mohamad Azhar

J. Cardiovasc. Dev. Dis. 2021, 8(3), 26; https://doi.org/10.3390/jcdd8030026 - 02 Mar 2021

Cited by 3 | Viewed by 2745

Abstract

Among the three transforming growth factor beta (TGFβ) ligands, TGFβ2 is essential for heart development and is produced by multiple cell types, including myocardium. Heterozygous mutations in TGFB2 in patients of connective tissue disorders result in congenital heart defects and adult valve malformations, including mitral valve prolapse (MVP) with or without regurgitation. Tgfb2 germline knockout fetuses exhibit multiple cardiac defects but the role of myocardial-TGFβ2 in heart development is yet to be elucidated. Here, myocardial Tgfb2 conditional knockout (CKO) embryos were generated by crossing Tgfb2^flox mice with Tgfb2^+/−; cTntCre mice. Tgfb2^flox/− embryos were normal, viable. Cell fate mapping was done using dual-fluorescent mT/mG^+/− mice. Cre-mediated Tgfb2 deletion was assessed by genomic PCR. RNAscope in situ hybridization was used to detect the loss of myocardial Tgfb2 expression. Histological, morphometric, immunohistochemical, and in situ hybridization analyses of CKOs and littermate controls at different stages of heart development (E12.5–E18.5) were used to determine the role of myocardium-derived TGFβ2 in atrioventricular (AV) cushion remodeling and myocardial development. CKOs exhibit a thin ventricular myocardium, AV cushion remodeling defects and developed incomplete AV septation defects. The loss of myocardial Tgfb2 resulted in impaired cushion maturation and dysregulated cell death. Phosphorylated SMAD2, a surrogate for TGFβ signaling, was “paradoxically” increased in both AV cushion mesenchyme and ventricular myocardium in the CKOs. Our results indicate that TGFβ2 produced by cardiomyocytes acting as cells autonomously on myocardium and via paracrine signaling on AV cushions are required for heart development. Full article

(This article belongs to the Special Issue Mitral Valve Development and Disease)

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8 pages, 700 KiB

Open AccessArticle

Assessment of D-Shaped Annulus of Mitral Valve in Patients with Severe MR Using Semi-Automated 4-Dimensional Analysis: Implications for Transcatheter Interventions

by N. Mai Vo, Suzanne E. van Wijngaarden, Nina Ajmone Marsan, Jeroen J. Bax and Victoria Delgado

J. Cardiovasc. Dev. Dis. 2020, 7(4), 48; https://doi.org/10.3390/jcdd7040048 - 01 Nov 2020

Cited by 3 | Viewed by 2678

Abstract

The development of transcatheter mitral valve replacement therapies requires accurate post-processing analysis tools to provide D-shaped mitral annulus dimensions from 3-dimensional (3D) data. The agreement between two semi-automated, software packages to process 3D transesophageal echocardiography (TEE) data for the measurement of the mitral valve annulus dimensions was evaluated. 3DTEE data of patients with moderate–severe mitral regurgitation (MR) were postprocessed with semi-automated, vendor-independent (VI) software and vendor-specific (VS) software. Both post-processing software provided key measurements for the selection of transcatheter valve prosthesis size: annulus area, annulus circumference and the septal-to-lateral distance of the annulus. The intertrigonal distance was provided only by the VS software. The inter- and intra-observer agreements were assessed with Bland–Altman analysis. Of 105 patients (63.8 ± 11 years, 66% male) with MR, 28 had secondary MR, 45 fibroelastic deficiency, and 32 Barlow’s disease. Using VS software, the dimensions for the overall population were 16.1 ± 4.6 cm² for annulus area, for circumference 14.4 ± 1.9 cm, intertrigonal distance 3.4 ± 0.5 cm and septal-to-lateral distance 3.8 ± 0.6 cm. Similar dimensions were obtained using VI software: 15.7 ± 4.6 cm² for annulus area, 14.5 ± 2.0 cm for circumference, and 4.1 ± 0.6 cm for septal-to-lateral distance. The inter- and intra-observer agreement for both software programs was excellent. In conclusion, current post-processing software programs for 3DTEE data of the mitral valve annulus provide good reproducibility of key measurements to select the transcatheter prosthesis size. Full article

(This article belongs to the Special Issue Mitral Valve Development and Disease)

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10 pages, 912 KiB

Open AccessEditor’s ChoiceArticle

Predictive Value of Pre-Operative 2D and 3D Transthoracic Echocardiography in Patients Undergoing Mitral Valve Repair: Long Term Follow Up of Mitral Valve Regurgitation Recurrence and Heart Chamber Remodeling

by Gloria Tamborini, Valentina Mantegazza, Marco Penso, Manuela Muratori, Laura Fusini, Sarah Ghulam Ali, Claudia Cefalù, Gianpiero Italiano, Valentina Volpato, Paola Gripari, Enrico G. Caiani, Marco Zanobini and Mauro Pepi

J. Cardiovasc. Dev. Dis. 2020, 7(4), 46; https://doi.org/10.3390/jcdd7040046 - 20 Oct 2020

Cited by 6 | Viewed by 2194

Abstract

The “ideal” management of asymptomatic severe mitral regurgitation (MR) in valve prolapse (MVP) is still debated. The aims of this study were to identify pre-operatory parameters predictive of residual MR and of early and long-term favorable remodeling after MVP repair. We included 295 patients who underwent MV repair for MVP with pre-operatory two- and three-dimensional transthoracic echocardiography (2DTTE and 3DTTE) and 6-months (6M) and 3-years (3Y) follow-up 2DTTE. MVP was classified by 3DTTE as simple or complex and surgical procedures as simple or complex. Pre-operative echo parameters were compared to post-operative values at 6M and 3Y. Patients were divided into Group 1 (6M-MR < 2) and Group 2 (6M-MR ≥ 2), and predictors of MR ≥ 2 were investigated. MVP was simple in 178/295 pts, and 94% underwent simple procedures, while in only 42/117 (36%) of complex MVP a simple procedure was performed. A significant relation among prolapse anatomy, surgical procedures and residual MR was found. Post-operative MR ≥ 2 was present in 9.8%: complex MVP undergoing complex procedures had twice the percentage of MR ≥ 2 vs. simple MVP and simple procedures. MVP complexity resulted independent predictor of 6M-MR ≥ 2. Favorable cardiac remodeling, initially found in all cases, was maintained only in MR < 2 at 3Y. Pre-operative 3DTTE MVP morphology identifies pts undergoing simple or complex procedures predicting MR recurrence and favorable cardiac remodeling. Full article

(This article belongs to the Special Issue Mitral Valve Development and Disease)

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16 pages, 3851 KiB

Open AccessArticle

Smooth Muscle α-Actin Expression in Mitral Valve Interstitial Cells is Important for Mediating Extracellular Matrix Remodeling

by Bailey K. Dye, Catalina Butler and Joy Lincoln

J. Cardiovasc. Dev. Dis. 2020, 7(3), 32; https://doi.org/10.3390/jcdd7030032 - 19 Aug 2020

Cited by 8 | Viewed by 3276

Abstract

Background: Mitral valve prolapse (MVP) affects 3–6% of the total population including those with connective tissue disorders. Treatment is limited, and patients commonly require surgery which can be impermanent and insuperable. Abnormal prolapse of mitral valve leaflets into the left atria is caused by disturbances to the composition and organization of the extracellular matrix (ECM), that weaken biomechanics. This process, known as myxomatous degeneration is characterized by an abnormal accumulation of proteoglycans, in addition to collagen fiber disruption and elastic fiber fragmentation. The underlying mechanisms that promote myxomatous degeneration to the point of biomechanical failure are unknown, but previous histological studies of end-stage diseased tissue have reported abnormal α-smooth muscle actin (SMA) in a subset of heart valve interstitial cells (VICs); however, the contribution of these abnormal cells to MVP pathogenesis has not been extensively examined. Methods: In vivo and in vitro approaches were used. Mice harboring a Fbn1^C1039G mutation mimic human Marfan Syndrome and develop MVP. Using these mice, temporal and spatial changes in SMA expression relative to myxomatous degeneration were examined using histological techniques. In parallel in vitro experiments, SMA expression was downregulated in primary porcine mitral VICs directly using siRNA, and indirectly using the actin depolymerizing agent Latrunculin A. In addition, the regulation of SMA in VICs by mechanical stiffness was explored relative to ECM remodeling. Results: We show, in mitral valves from Fbn1^C1039G/+ mice, that abnormal increases in SMA expression in VICs are evident during early postnatal stages of disease, prior to significant myxomatous degeneration as indicated at later stages by increased proteoglycans and collagen type I (Col1a1). Furthermore, abnormal SMA expression continues to increase during the course of pathogenesis and is localized to the mid belly region of the mitral valve leaflets from 10 weeks. Using an in vitro approach, we demonstrate that reduced SMA function by direct siRNA or indirect Latrunculin A treatment attenuates proteoglycan and Col1a1 expression in porcine mitral VICs. While upstream, we provide insights to show that SMA is regulated by mechanical tension in VICs to promote changes in ECM homeostasis. Conclusions: Together, our data show that in VICs, SMA, an actin binding protein, is important for mediating ECM remodeling associated with phenotypes observed in myxomatous degeneration, and its expression is regulated by mechanical tension. These novel insights could inform the development of future non-surgical therapeutics to halt the progression of mitral valve degeneration thereby avoiding end-stage prolapse. Full article

(This article belongs to the Special Issue Mitral Valve Development and Disease)

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17 pages, 9803 KiB

Open AccessArticle

Dynamic Expression Profiles of β-Catenin during Murine Cardiac Valve Development

by Lilong Guo, Janiece Glover, Alyssa Risner, Christina Wang, Diana Fulmer, Kelsey Moore, Cortney Gensemer, Mary Kate Rumph, Reece Moore, Tyler Beck and Russell A. Norris

J. Cardiovasc. Dev. Dis. 2020, 7(3), 31; https://doi.org/10.3390/jcdd7030031 - 17 Aug 2020

Cited by 3 | Viewed by 3484

Abstract

β-catenin has been widely studied in many animal and organ systems across evolution, and gain or loss of function has been linked to a number of human diseases. Yet fundamental knowledge regarding its protein expression and localization remains poorly described. Thus, we sought to define whether there was a temporal and cell-specific regulation of β-catenin activities that correlate with distinct cardiac morphological events. Our findings indicate that activated nuclear β-catenin is primarily evident early in gestation. As development proceeds, nuclear β-catenin is down-regulated and becomes restricted to the membrane in a subset of cardiac progenitor cells. After birth, little β-catenin is detected in the heart. The co-expression of β-catenin with its main transcriptional co-factor, Lef1, revealed that Lef1 and β-catenin expression domains do not extensively overlap in the cardiac valves. These data indicate mutually exclusive roles for Lef1 and β-catenin in most cardiac cell types during development. Additionally, these data indicate diverse functions for β-catenin within the nucleus and membrane depending on cell type and gestational timing. Cardiovascular studies should take into careful consideration both nuclear and membrane β-catenin functions and their potential contributions to cardiac development and disease. Full article

(This article belongs to the Special Issue Mitral Valve Development and Disease)

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Review

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8 pages, 1069 KiB

Open AccessReview

Collagen Fibrillogenesis in the Mitral Valve: It’s a Matter of Compliance

by Richard L. Goodwin, Arash Kheradvar, Russell A. Norris, Robert L. Price and Jay D. Potts

J. Cardiovasc. Dev. Dis. 2021, 8(8), 98; https://doi.org/10.3390/jcdd8080098 - 20 Aug 2021

Cited by 4 | Viewed by 2551

Abstract

Collagen fibers are essential structural components of mitral valve leaflets, their tension apparatus (chordae tendineae), and the associated papillary muscles. Excess or lack of collagen fibers in the extracellular matrix (ECM) in any of these structures can adversely affect mitral valve function. The organization of collagen fibers provides a sophisticated framework that allows for unidirectional blood flow during the precise opening and closing of this vital heart valve. Although numerous ECM molecules are essential for the differentiation, growth, and homeostasis of the mitral valve (e.g., elastic fibers, glycoproteins, and glycans), collagen fibers are key to mitral valve integrity. Besides the inert structural components of the tissues, collagen fibers are dynamic structures that drive outside-to-inside cell signaling, which informs valvular interstitial cells (VICs) present within the tissue environment. Diversity of collagen family members and the closely related collagen-like triple helix-containing proteins found in the mitral valve, will be discussed in addition to how defects in these proteins may lead to valve disease. Full article

(This article belongs to the Special Issue Mitral Valve Development and Disease)

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14 pages, 1732 KiB

Open AccessEditor’s ChoiceReview

Characterization of Degenerative Mitral Valve Disease: Differences between Fibroelastic Deficiency and Barlow’s Disease

by Aniek L. van Wijngaarden, Boudewijn P. T. Kruithof, Tommaso Vinella, Daniela Q. C. M. Barge-Schaapveld and Nina Ajmone Marsan

J. Cardiovasc. Dev. Dis. 2021, 8(2), 23; https://doi.org/10.3390/jcdd8020023 - 22 Feb 2021

Cited by 27 | Viewed by 6987

Abstract

Degenerative mitral valve disease causing mitral valve prolapse is the most common cause of primary mitral regurgitation, with two distinct phenotypes generally recognized with some major differences, i.e., fibroelastic deficiency (FED) and Barlow’s disease. The aim of this review was to describe the main histological, clinical and echocardiographic features of patients with FED and Barlow’s disease, highlighting the differences in diagnosis, risk stratification and patient management, but also the still significant gaps in understanding the exact pathophysiology of these two phenotypes. Full article

(This article belongs to the Special Issue Mitral Valve Development and Disease)

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15 pages, 2732 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Myxomatous Mitral Valve Disease with Mitral Valve Prolapse and Mitral Annular Disjunction: Clinical and Functional Significance of the Coincidence

by Nina C. Wunderlich, Siew Yen Ho, Nir Flint and Robert J. Siegel

J. Cardiovasc. Dev. Dis. 2021, 8(2), 9; https://doi.org/10.3390/jcdd8020009 - 24 Jan 2021

Cited by 17 | Viewed by 6815

Abstract

The morphological changes that occur in myxomatous mitral valve disease (MMVD) involve various components, ultimately leading to the impairment of mitral valve (MV) function. In this context, intrinsic mitral annular abnormalities are increasingly recognized, such as a mitral annular disjunction (MAD), a specific anatomical abnormality whereby there is a distinct separation between the mitral annulus and the left atrial wall and the basal portion of the posterolateral left ventricular myocardium. In recent years, several studies have suggested that MAD contributes to myxomatous degeneration of the mitral leaflets, and there is growing evidence that MAD is associated with ventricular arrhythmias and sudden cardiac death. In this review, the morphological characteristics of MAD and imaging tools for diagnosis will be described, and the clinical and functional aspects of the coincidence of MAD and myxomatous MVP will be discussed. Full article

(This article belongs to the Special Issue Mitral Valve Development and Disease)

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22 pages, 1928 KiB

Open AccessEditor’s ChoiceReview

Biology and Biomechanics of the Heart Valve Extracellular Matrix

by Karthik M. Kodigepalli, Kaitlyn Thatcher, Toni West, Daniel P. Howsmon, Frederick J. Schoen, Michael S. Sacks, Christopher K. Breuer and Joy Lincoln

J. Cardiovasc. Dev. Dis. 2020, 7(4), 57; https://doi.org/10.3390/jcdd7040057 - 16 Dec 2020

Cited by 36 | Viewed by 7087

Abstract

Heart valves are dynamic structures that, in the average human, open and close over 100,000 times per day, and 3 × 10⁹ times per lifetime to maintain unidirectional blood flow. Efficient, coordinated movement of the valve structures during the cardiac cycle is mediated by the intricate and sophisticated network of extracellular matrix (ECM) components that provide the necessary biomechanical properties to meet these mechanical demands. Organized in layers that accommodate passive functional movements of the valve leaflets, heart valve ECM is synthesized during embryonic development, and remodeled and maintained by resident cells throughout life. The failure of ECM organization compromises biomechanical function, and may lead to obstruction or leaking, which if left untreated can lead to heart failure. At present, effective treatment for heart valve dysfunction is limited and frequently ends with surgical repair or replacement, which comes with insuperable complications for many high-risk patients including aged and pediatric populations. Therefore, there is a critical need to fully appreciate the pathobiology of biomechanical valve failure in order to develop better, alternative therapies. To date, the majority of studies have focused on delineating valve disease mechanisms at the cellular level, namely the interstitial and endothelial lineages. However, less focus has been on the ECM, shown previously in other systems, to be a promising mechanism-inspired therapeutic target. Here, we highlight and review the biology and biomechanical contributions of key components of the heart valve ECM. Furthermore, we discuss how human diseases, including connective tissue disorders lead to aberrations in the abundance, organization and quality of these matrix proteins, resulting in instability of the valve infrastructure and gross functional impairment. Full article

(This article belongs to the Special Issue Mitral Valve Development and Disease)

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16 pages, 6142 KiB

Open AccessReview

Anatomy of Mitral Valve Complex as Revealed by Non-Invasive Imaging: Pathological, Surgical and Interventional Implications

by Laura Anna Leo, Vera Lucia Paiocchi, Susanne Anna Schlossbauer, Elisa Gherbesi and Francesco F. Faletra

J. Cardiovasc. Dev. Dis. 2020, 7(4), 49; https://doi.org/10.3390/jcdd7040049 - 04 Nov 2020

Cited by 5 | Viewed by 4468

Abstract

Knowledge of mitral valve (MV) anatomy has been accrued from anatomic specimens derived by cadavers, or from direct inspection during open heart surgery. However, today two-dimensional and three-dimensional transthoracic (2D/3D TTE) and transesophageal echocardiography (2D/3D TEE), computed tomography (CT) and cardiac magnetic resonance (CMR) provide images of the beating heart of unprecedented quality in both two and three-dimensional format. Indeed, over the last few years these non-invasive imaging techniques have been used for describing dynamic cardiac anatomy. Differently from the “dead” anatomy of anatomic specimens and the “static” anatomy observed during surgery, they have the unique ability of showing “dynamic” images from beating hearts. The “dynamic” anatomy gives us a better awareness, as any single anatomic arrangement corresponds perfectly to a specific function. Understanding normal anatomical aspects of MV apparatus is of a paramount importance for a correct interpretation of the wide spectrum of patho-morphological MV diseases. This review illustrates the anatomy of MV as revealed by non-invasive imaging describing physiological, pathological, surgical and interventional implications related to specific anatomical features of the MV complex. Full article

(This article belongs to the Special Issue Mitral Valve Development and Disease)

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Other

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6 pages, 3042 KiB

Open AccessCase Report

Malignant Arrhythmic Mitral Valve Prolapse: A Continuum of Clinical Challenges from Diagnosis to Risk Stratification and Patient Management

by Idit Yedidya, Aniek L. van Wijngaarden and Nina Ajmone Marsan

J. Cardiovasc. Dev. Dis. 2021, 8(1), 2; https://doi.org/10.3390/jcdd8010002 - 29 Dec 2020

Cited by 1 | Viewed by 4925

Abstract

Mitral valve prolapse (MVP) is a common valvular disease, which may remain a benign condition for a long period of time. However, some patients experience malignant ventricular arrhythmias and sudden cardiac death (SCD). It is still largely unknown how to risk-stratify these patients, and no specific recommendations have been proposed to help the clinical decision-making. We present the case of a young man whose first clinical presentation was an out-of-hospital cardiac arrest and was subsequently diagnosed with MVP. We highlighted the possible risk factors for SCD and the challenges in the clinical management of these patients. Full article

(This article belongs to the Special Issue Mitral Valve Development and Disease)

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5 pages, 1435 KiB

Open AccessCase Report

Early Basal Cuspal Tear of a Porcine Bioprosthetic Mitral Valve Causing Massive Mitral Regurgitation

by Muhammed Tamim, Christos Alexiou, Yaser AlKadi, Mohsen S. Mahmoud and Fatema Qaddoura

J. Cardiovasc. Dev. Dis. 2020, 7(4), 52; https://doi.org/10.3390/jcdd7040052 - 06 Nov 2020

Viewed by 1957

Abstract

Although porcine mitral bioprostheses provide predictably good long-term outcomes, unexpected leaflet tears leading to abrupt haemodynamic changes may occur. Here, we report on a patient who was presented with acute dyspnea due to a cuspal tear of a porcine bioprosthetic mitral valve causing severe mitral regurgitation. Her condition was subsequently complicated by a systemic infection, probably pneumonia, and was successfully managed with an urgent redo-mitral valve replacement. Full article

(This article belongs to the Special Issue Mitral Valve Development and Disease)

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