Diagnostic Management and Surgical Treatment of Isolated Tricuspid Regurgitation

Severe tricuspid regurgitation is especially caused by pulmonary hypertension. Primary tricuspid regurgitation in the absence of pulmonary hypertension and of unknown etiology is a very rare condition with scarce data about its diagnosis, treatment, and follow-up. The particularities of surgery indication and outcomes are still not clearly known. A 72-year-old woman with a medical history of coronary artery bypass grafting three years ago presented with shortness of breath and low limb edema. Physical examination revealed a prominent bilateral jugular turgescence, hepatomegaly, peripheral edema, and a left midsternal border holosystolic murmur, suggestive of tricuspid regurgitation. The echocardiogram confirmed the diagnosis and showed preserved right and left ventricular dimensions and function. Coronary angiography showed no new obstructive lesions and patent surgical grafts. Right cardiac catheterization revealed mild pulmonary hypertension and increased right atrium pressure. Cardiac magnetic resonance showed mild right ventricular dilation with normal systolic function and normal left chambers. No late gadolinium enhancement was detected. Because of persistent symptoms, even after optimization of medical therapy, the patient was submitted to tricuspid valve replacement surgery. Immediately after the surgery, the patient developed significant right ventricular dysfunction, with the need of continuous hemodynamic support. She had progressive clinical recovery that was confirmed by serial echocardiograms that showed improvement in right ventricular volume and function. The patient was discharged with no signs or symptoms of right heart failure. The histopathological examination showed significant and diffuse myxomatous degeneration of the leaflets. No signs of infection or vegetation nor disruption of strands were observed. This report illustrates a very rare case of symptomatic primary isolated severe tricuspid regurgitation caused by myxomatous degeneration of the leaflets. The thoroughly diagnostic workup is presented, and only the histopathological analysis of the leaflets revealed the etiologic process. Surgical treatment indicated before the onset of right ventricular failure was essential to patient’s full recovery.

Ethyl acetate fraction of Cola hispida leaf protects against doxorubicin-induced myocardial injury in male albino rats

Background Cardiovascular diseases have continued to be the leading cause of death globally. In addition, some of the drugs used in the treatment of the diseases present some adverse effects which limit the usefulness of such drugs. Thus, there is a need for novel drugs whose side effect is either minimal or non-existent. The presence of bioactive compounds in Cola hispida leaf is of great significance in the treatment and management of cardiovascular conditions. This study investigated the cardio-protective potential against doxorubicin (Dox)-induced cardiac infarction in rats. Results Dox induction resulted to muscle fiber degeneration in Dox-treated rats hence revealed significant (p < 0.05) elevation in the serum level of cardio biomarker enzymes and lipid peroxidation profile while significant (p < 0.05) fall in cardiac enzymatic antioxidant levels were observed relative to the normal control. Pre-treatment with ethyl acetate fraction of Cola hispida leaf expressed cardio-protective potentials against Dox-induced cardiotoxicity by significantly (p < 0.05) lowering the levels of cardiac biomarker enzymes towards normal, building up the activities of subdued antioxidant enzymes and depleting its malondialdehyde level. Histopathology photomicrograph of the heart tissues expressed myxomatous degeneration but was ameliorated through the administration of the fraction. Conclusion In accordance with the findings from this study, the administration of ethyl acetate fraction of Cola hispida leaf is effective against Dox-induced redox imbalance due to its enriched antioxidant phytoconstituents.

Activation of the Interleukin-33/ST2 Pathway Exerts Deleterious Effects in Myxomatous Mitral Valve Disease

Mitral valve disease (MVD) is a frequent cause of heart failure and death worldwide, but its etiopathogenesis is not fully understood. Interleukin (IL)-33 regulates inflammation and thrombosis in the vascular endothelium and may play a role in the atherosclerotic process, but its role in mitral valve has not been investigated. We aim to explore IL-33 as a possible inductor of myxomatous degeneration in human mitral valves. We enrolled 103 patients suffering from severe mitral regurgitation due to myxomatous degeneration undergoing mitral valve replacement. Immunohistochemistry of the resected leaflets showed IL-33 and ST2 expression in both valve interstitial cells (VICs) and valve endothelial cells (VECs). Positive correlations were found between the levels of IL-33 and molecules implicated in the development of myxomatous MVD, such as proteoglycans, extracellular matrix remodeling enzymes (matrix metalloproteinases and their tissue inhibitors), inflammatory and fibrotic markers. Stimulation of single cell cultures of VICs and VECs with recombinant human IL-33 induced the expression of activated VIC markers, endothelial–mesenchymal transition of VECs, proteoglycan synthesis, inflammatory molecules and extracellular matrix turnover. Our findings suggest that the IL-33/ST2 system may be involved in the development of myxomatous MVD by enhancing extracellular matrix remodeling.

CLINICAL FEATURES AND RISK FACTORS OF EMERGENCE AND DEVELOPMENT OF ATRIOVENTRICULAR VALVE DEGENERATION IN DOGS

The study of cardiovascular diseases in small domestic animals is an urgent problem of modern veterinary medi-cine. The research goal is to develop a science-based ap-proach to the clinical picture and risk factors of the emer-genceand development of atrioventricular valve degenera-tion in dogs. The study was conducted in the Department of Biology and Pathology of Small Domestic, Laboratory and Exotic Animals of the Moscow State Academy of Vet-erinary Medicine and Biotechnology named after K.I. Skryabin. The research targets were 162 dogs with myx-omatous degeneration of atriovetricular valves. Myxoma-tous degeneration of the valvular heart apparatus was more often found in dogs of the age of 7 to 10 years -61.7%. The cases were most often diagnosed in dogs of the breeds Chihuahua -29.63%, and Yorkshire Terrier-21%. Of the total number of animals, the disease was more common in males -69.14%. Clinical signs of myxomatous degeneration of the valvular heart apparatus in dogs were diverse. The objective diagnostic clinical signs of myxoma-tous degeneration of the mitral valve of the heart in dogs were the following: cough (53%), sudden lethargy (48%), dyspnea (26%); less frequently -weight loss (12%), loss of consciousness (2.21%) and ascites (0.74%). The main clinical signs of tricuspid valve damage were the following ones: cough (57.14%) and ascites (42.86%). Dyspnea and loss of consciousness were less common (14.29%). With a combined damage of the mitral and tricuspid valves, the clinical picture was more pronounced. The most common symptoms were cough (84.21%), dyspnea (73.68%), and sudden lethargy (63.16%). The clinical substantiation for the development of myxomatous degeneration of the valvu-lar heart apparatus in dogs is the following factors: age, breed and sex of the animal. The clinical signs and differ-ential diagnostic criteria were characterized by polymor-phism and differed in cases of mitral and tricuspid valve lesions and their joint degeneration.

Risk factors of persistent ventricular arrhythmias after mitral valve repair in Barlow disease patients: six-year follow-up

Funding Acknowledgements Type of funding sources: None. Introduction Improvement in malignant ventricular arrhythmias (VA) has been reported after mitral valve surgery in some mitral valve prolapse patients (MVP) with severe degenerative mitral regurgitation. Mitral annular disjunction, posterior systolic curling, and mitral annular abnormal contractility are associated with arrhythmic MVP and underwent correction during the mitral valve repair. However, mitral valve disease progression and ventricular arrhythmic substrates (left ventricular fibrosis of papillary muscles and basal posterior wall) could be potential substrates for persistent malignant arrhythmias even after surgical correction. Our aim was to evaluate the risk factors of persistent VA after mitral valve repair in Barlow’s disease patients in six-year follow-up. Methods 30 consecutive patients (mean age 53.1 ± 9.4, 47% male) who underwent mitral valve repair for severe mitral regurgitation (MR) due to mitral valve prolapse were enrolled in our observational, prospective, single-center study. Resected abnormal segments of the mitral leaflets were examined by experienced pathologists for signs of myxomatous degeneration. Transthoracic echocardiography and 24-hour Holter monitoring were performed pre- and postoperatively annually. PVCs and nonsustained ventricular tachycardia (VT) runs were reviewed. Results All patients survived the operation. There was only one sudden cardiac death on sixth year of follow-up. During 173 person-years of follow-up 3 patients (10%) had developed recurrent moderate to severe (≥2) MR. The total number of PVCs and non-sustained ventricular tachycardia runs dropped significantly in 1st (p=.04, Wilcoxon matched pairs test) and 2nd (p=.03), years of postoperative follow-up. Postoperative incidence of PVCs and VT correlated strongly with postoperative end-diastolic LV diameter (EDD rs=.69; p=.005), moderate negatively with LV ejection fraction (EF rs=-.55; p=.001). Advanced myxomatous degeneration assessed by pathologists and MV posterior leaflet’s thickness ≥5 mm after repair assessed by echocardiographer associated with postoperative PVCs and VT (rτ=.58; p=.045 and rs=.62; p=.002, respectively). Recurrent MR also strongly associated with postoperative PVCs and VT (rs=.76; p=.0018). In univariate analysis, advanced myxomatous degeneration (p=.008), postoperative end-diastolic LV diameter (p=.001), and low EF (p=.003) were identified as risk factors of persistent PVCs/VT after surgery. Conclusions Advanced myxomatous degeneration assessed by pathologists or echocardiographer and postoperative left ventricular remodeling are associated with persistent malignant ventricular arrhythmias. Further investigation in larger cohorts to evaluate the association between degenerative mitral valve disease and ventricular arrhythmias is needed.

A case of finding of asymptomatic 3rd stage myxomatous degeneration of the mitral valve in general practice

The case of asymptomatic 3rd stage myxomatous degeneration of the mitral valve in a 42-year old male patient is presented. The patient was referred to Tuberculosis dispensary No. 5 for investigation of pathological findings revealed by fluorography during the coronavirus pandemic period. The patient was examined by TB specialists and the general practitioner in accordance with new interdisciplinary diagnostic algorithms primary involving the GP. As а result of the detailed investigation the patient was found to have previously undiagnosed consequences of pneumonia caused by COVID-19 and 3rd stage myxomatous degeneration of the mitral valve.

New insights into the pathophysiology of mitral valve disease: molecular characterisation and comparison of the different aetiologic subtypes

Introduction Mitral valve disease (MVD) is a frequent cause of heart failure and death. Data regarding its molecular basis are scarce, although current evidences show that primary MVD is an active process with the involvement of several molecular pathways. However, there are no studies that compare such mechanisms among the different subtypes of primary MVD. ST-2/interleukin (IL)-33 pathway is a potential pathophysiological mediator of cardiovascular diseases, although its role in heart valve diseases has not been explored. Purpose We aimed to analyse the molecular and cellular mechanisms involved in the main subtypes of primary chronic MVD: myxomatous degeneration, calcific or senile degeneration and rheumatic MVD. Methods 200 patients undergoing mitral valve replacement due to chronic primary MVD were enrolled. We classified them in the three main aetiologic subtypes according to echocardiographic features and surgeon's description: myxomatous degeneration (89 patients), senile or calcific degeneration (54 patients) and rheumatic disease (57 patients). In all patients the resected valve tissue and blood samples were collected. RT-PCR, Western Blot and ELISA were performed to analyse markers of inflammation (C-reactive protein, Rantes, IL-6, IL-1β/IL-1F2, tumor necrosis factor (TNF)-α), calcification (osteopontin, bone morphogenic protein (BMP)-2 and -4 and periostin), valvular endothelial cells (CD-31, E-cadherin), extracellular matrix remodeling (matrix metalloproteinase (MMP)-1, -2 and -9, tissue inhibitor of MMP-1 and -2), proteoglycans (aggrecan, hyaluronan, lumican, biglycan, syndecan-1, decorin) fibrosis (collagen-1, fibronectin, galectin-3, Transforming growth factor (TGF)-β) and ST-2/IL-33 system. Results Each aetiologic subtype showed a distinct marker profile. As compared with the other subtypes, myxomatous valves presented significantly higher levels of inflammatory markers (Rantes, IL-6), fibronectin, proteoglycans (hyaluronan, lumican and biglycan), ST-2 and IL-33. Senile degenerative valves presented significantly higher levels of calcification markers (osteopontin, BMP-2 and -4). Rheumatic valves were characterized by high levels of TNF-α and TGF-β compared to other subtypes and a significant increase in the expression and activity of matrix degradation enzymes (MMP-1 and -2). Conclusions Our study provides for the first time the molecular characterisation of the main aetiologic subtypes of chronic MVD. Proteoglycans accumulation, fibrosis and inflammation are the main features of myxomatous changes, whereas calcification define senile degeneration. Rheumatic valves exhibit elevated TNF-α and TGF-β and a dramatic increase in matrix turnover. Moreover, myxomatous valves overexpress the ST-2/IL-33 system, suggesting that this pathway could play a role in the development of myxomatous changes. Unravelling the underlying molecular mechanisms of each aetiology is essential to identify new therapeutic targets. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Fondo de Investigaciones Sanitarias

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

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 Fbn1C1039G 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 Fbn1C1039G/+ 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.