Impact of Tricuspid Regurgitation on Outcomes After Transcatheter Mitral Valve Replacement.

Development of functional tricuspid regurgitation (TR) because of chronic mitral disease and subsequent heart failure is common. However, the effect of TR on clinical outcomes after transcatheter mitral valve replacement (TMVR) remains unclear. We aimed to evaluate the impact of baseline TR on outcomes after TMVR. This was a single-center, retrospective analysis of patients who received valve-in-valve or valve-in-ring TMVR between 2012 and 2022. Patients were categorized into none/mild TR and moderate/severe TR based on baseline echocardiography. The primary outcome was 3 years all-cause death and the secondary outcomes were in-hospital events. Of the 135 patients who underwent TMVR, 64 (47%) exhibited none/mild TR at baseline, whereas 71 (53%) demonstrated moderate/severe TR. There were no significant differences in in-hospital events between the groups. At 3 years, the moderate/severe TR group exhibited a significantly increased risk of all-cause death (adjusted hazard ratio 3.37, 95% confidence interval 1.35 to 8.41, p = 0.009). When patients with baseline moderate/severe TR were stratified by echocardiography at 30 days into improved (36%) and nonimproved (64%) TR groups, although limited by small sample size, there was no significant difference in 3-year all-cause mortality (p = 0.48). In conclusion, this study investigating the impact of baseline TR on clinical outcomes revealed that moderate/severe TR is prevalent in those who underwent TMVR and is an independent predictor of 3-year all-cause mortality. Earlier mitral valve intervention before the development of significant TR may play a pivotal role in improving outcomes after TMVR.

A systematic review of present and future pharmaco-structural therapies for hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are ubiquitous, they are limited by a lack of solid evidence, are often inadequate, poorly tolerated, and do not alter the natural disease course. As such, there has long been a need for effective, evidence-based, and targeted disease-modifying therapies for HCM. In this review, we redefine HCM as a treatable condition, evaluate current strategies for therapeutic intervention, and discuss novel myosin inhibitors. The majority of patients with HCM have elevated left ventricular outflow tract gradients, which predicts worse symptoms and adverse outcomes. Conventional pharmacological therapies for symptomatic HCM can help improve symptoms but are often inadequate and poorly tolerated. Septal reduction therapies (surgical myectomy and alcohol septal ablation) can safely and effectively reduce refractory symptoms and improve outcomes in patients with obstructive HCM. However, they require expertise that is not universally available and are not without risks. Currently, available therapies do not alter the disease course or the progressive cardiac remodeling that ensues, nor subsequent heart failure and arrhythmias. This has been regarded as an unmet need in the care of HCM patients. Novel targeted pharmacotherapies, namely cardiac myosin inhibitors, have emerged to reverse key pathophysiological changes and alter disease course. Their favorable outcomes led to the early Food and Drug Administration approval of mavacamten, a first-in-class myosin modulator, changing the paradigm for the pharmacological treatment of HCM.

Osteocytes serve as a progenitor cell of osteosarcoma.

Osteosarcoma (OSA) is the most common primary bone tumor in humans. However, the cell of origin of OSA is not clearly defined although there is evidence that osteoblasts may serve as OSA progenitors. The role of osteocytes, terminally differentiated osteoblasts, as OSA progenitors has yet to be described. Analysis of patient cDNA from publicly available microarray data revealed that patients with OSA have increased expression of dentin matrix phosphoprotein 1 (DMP1), a marker of osteocytes. Analysis of multiple murine, human, and canine OSA cell lines revealed DMP1 expression. To test the tumorigenic potential of osteocytes, MLO-Y4, a SV-40 immortalized murine osteocyte cell line, was injected into subcutaneous and orthotopic (intratibial) sites of mice. Tumor growth occurred in both locations. Orthotopic MLO-Y4 tumors produced mixed osteoblastic/osteolytic radiographic lesions; a hallmark of OSA. Together, these data demonstrate for the first time that osteocytes can serve as OSA progenitors.