Differential Requirement of DICER1 Activity during Development of Mitral and Tricuspid Valves

Mitral and tricuspid valves are essential for unidirectional blood flow in the heart. They are derived from similar cell sources, and yet congenital dysplasia affecting both valves is clinically rare, suggesting the presence of differential regulatory mechanisms underlying their development. We specifically inactivated Dicer1 in the endocardium during cardiogenesis, and unexpectedly found that Dicer1-deletion caused congenital mitral valve stenosis and regurgitation, while it had no impact on other valves. We showed that hyperplastic mitral valves were caused by abnormal condensation and extracellular matrix (ECM) remodeling. Our single-cell RNA Sequencing analysis revealed impaired maturation of mesenchymal cells and abnormal expression of ECM genes in mutant mitral valves. Furthermore, expression of a set of miRNAs that target ECM genes was significantly lower in tricuspid valves compared to mitral valves, consistent with the idea that the miRNAs are differentially required for mitral and tricuspid valve development. Our study thus reveals miRNA-mediated gene regulation as a novel molecular mechanism that differentially regulates mitral and tricuspid valve development, thereby enhancing our understanding of the non-association of inborn mitral and tricuspid dysplasia observed clinically.

Hybrid Surgery for Severe Mitral Valve Calcification: Limitations and Caveats for an Open Transcatheter Approach

Background and Objectives: Mitral stenosis with extensive mitral annular calcification (MAC) remains surgically challenging in respect to clinical outcome. Prolonged surgery time with imminent ventricular rupture and systolic anterior motion can be considered as a complex of causal factors. The aim of our alternative hybrid approach was to reduce the risk of annual rupture and paravalvular leaks and to avoid obstruction of the outflow tract. A review of the current literature was also carried out. Materials and Methods: Six female patients (mean age 76 ± 9 years) with severe mitral valve stenosis and severely calcified annulus underwent an open implantation of an Edwards Sapien 3 prosthesis on cardiopulmonary bypass. Our hybrid approach involved resection of the anterior mitral leaflet, placement of anchor sutures and the deployment of a balloon expanded prosthesis under visual control. Concomitant procedures were carried out in three patients. Results: The mean duration of cross-clamping was 95 ± 31 min and cardiopulmonary bypass was 137 ± 60 min. The perioperative TEE showed in three patients an inconspicuous, heart valve-typical gradient on all implanted prostheses and a clinically irrelevant paravalvular leakage occurred in the anterior annulus. In the left ventricular outflow tract, mild to moderately elevated gradients were recorded. No adverse cerebrovascular events and pacemaker implantations were observed. All but one patient survived to discharge. Survival at one year was 83.3%. Conclusions: This “off label” implantation of the Edwards Sapien 3 prosthesis may be considered as a suitable bail-out approach for patients at high-risk for mitral valve surgery or deemed inoperable due to extensive MAC.

Cor triatriatum sinister in a 36-Year-old male with Metabolic Syndrome: A case report in sub-Saharan Africa.

We report the first case of isolated Cor triatriatum sinister in a 36-year-old male with metabolic syndrome in sub-Saharan Africa. It is a rare congenital heart disease that consists of a fibromuscular ring that divides the atrium into two chambers. It can mimic mitral valve stenosis.

Randomised controlled trial into the role of ramipril in fibrosis reduction in rheumatic heart disease: the RamiRHeD trial protocol

IntroductionRheumatic heart disease (RHD) is a major burden in developing countries and accounts for 80% of all people living with the disease, where it causes most cardiovascular morbidity and mortality in children and young adults. Chronic inflammation and fibrosis of heart valve tissue due to chronic inflammation in RHD will cause calcification and thickening of the impacted heart valves, especially the mitral valve. This fibrogenesis is enhanced by the production of angiotensin II by increased transforming growth factor β expression and later by the binding of interleukin-33, which is known to have antihypertrophic and antifibrotic effects, to soluble sST2. sST2 binding to this non-natural ligand worsens fibrosis. Therefore, we hypothesise that ACE inhibitors (ACEIs) would improve rheumatic mitral valve stenosis.Methods and analysisThis is a single-centre, double-blind, placebo-controlled, randomised clinical trial with a pre–post test design. Patients with rheumatic mitral stenosis and valve dysfunction will be planned for cardiac valve replacement operation and will be given ramipril 5 mg or placebo for a minimum of 12 weeks before the surgery. The expression of ST2 in the mitral valve is considered to be representative of cardiac fibrosis. Mitral valve tissue will be stained by immunohistochemistry to ST2. Plasma ST2 will be measured by ELISA. This study is conducted in the Department of Cardiology and Vascular Medicine, Universitas Indonesia, National Cardiac Center Harapan Kita Hospital, Jakarta, Indonesia, starting on 27 June 2019.Ethics and disseminationThe performance and dissemination of this study were approved by the ethics committee of National Cardiovascular Center Harapan Kita with ethical code LB.02.01/VII/286/KEP.009/2018.Trial registration numberNCT03991910.

A Case of Massive Left Atrial Thrombus

Rheumatic heart disease is the most common cause of mitral valve stenosis. Left atrial appendage thrombus is associated with mitral stenosis, but in rare cases the thrombus can extend to the left atrial cavity. We present a case of a severe rheumatic mitral stenosis and associated large left atrial thrombus, with embolic sequelae.

Combined Aortic and Mitral Valve Stenosis in Mucopolysaccharidosis Syndrome Type I-S: A Report of a Rare Case

Mucopolysaccharidosis (MPS) syndrome is an inherited metabolic disorder. In more than half of the patients with MPS syndrome, heart valve involvement is reported; however, combined aortic and mitral valve stenosis in MPS syndrome type I-S is very rare. We describe a 39-year-old man with severe mitral and aortic valve stenosis due to MPS syndrome type I-S. Transthoracic and transesophageal echocardiography revealed severe thickening and calcification in the aortic and mitral valves with severe left ventricular hypertrophy. The coronary arteries were normal in angiography.

Outcomes Following Surgery to Address Shone Syndrome in Children

Background: Shone syndrome is characterized by coincident mitral valve stenosis and left ventricular outflow tract obstruction. Although first described in 1963, little research has expounded surgical outcomes. We sought to evaluate our experience with this cohort, emphasizing outcomes including mortality, morbidity, and cardiac function. Methods: A retrospective chart review of 46 patients who underwent operation for Shone syndrome between 1990 and May 2018 was conducted. Index operations included 32 repairs of the left ventricular outflow tract, four mitral valve repair/replacements, nine combined repairs, and one non-Shone’s repair. Median age at index procedure was 22 days (2 days-10 years). Mean follow-up was 9.1 years (2 months-21 years), and 70 additional operations (51 reoperations) were required. Three patients were lost to follow-up. Results: Overall survival was 95.7% with two late deaths. Freedom from death or transplant was 93.5%. Thirteen (28.3%) patients remained free from reoperation. Thirty-three patients required 51 reoperations of the left ventricle outflow tract (n = 12), mitral valve (n = 16), combined repairs (n = 21), and transplant (n = 1). At most recent follow-up, patients exhibited mitral stenosis (n = 21), aortic stenosis (n = 7), and diminished LV function (n = 2). Conclusion: Surgical correction of Shone’s offers excellent survival benefit, but reoperation burden is high, with >70% of patients requiring reintervention in the follow-up period. A total of 65% of patients developed recurrent obstruction of left ventricular inflow or outflow, however, ventricular function is preserved in the majority of patients. All but one patient had no functional deficits, classified as New York Heart Association I with > 60% requiring no medication.