Transcatheter Mitral Valve Replacement Using Transcatheter Aortic Valve or Dedicated Devices: Current Evidence and Future Prospects.

Transcatheter mitral valve replacement (TMVR) is a novel and evolving field dedicated to addressing the therapeutic challenges posed by patients at high surgical risk with mitral valve disease. TMVR can be categorized into two distinct fields based on the type of device and its specific indications: TMVR with transcatheter aortic valves (TAV) and TMVR with dedicated devices. Similar to aortic stenosis, TMVR with TAV requires a rigid support structure to secure the valve in place. As a result, it is indicated for patients with failing bioprothesis or surgical rings or mitral valve disease associated with severe mitral annular calcification (MAC), which furnishes the necessary foundation for valve anchoring. While TMVR with TAV has shown promising outcomes in valve-in-valve procedures, its effectiveness remains more contentious in valve-in-ring or valve-in-MAC procedures. Conversely, TMVR with dedicated devices seeks to address native mitral regurgitation, whether accompanied by MAC or not, providing an alternative to Transcatheter Edge-to-Edge Repair (TEER) when TEER is not feasible or expected to yield unsatisfactory results. This emerging field is gradually surmounting technical challenges, including anchoring a valve in a non-calcified annulus and transitioning from the transapical route to the transeptal approach. Numerous devices are presently undergoing clinical trials. This review aims to furnish an overview of the supporting evidence for TMVR using TAV in each specific indication (valve-in-valve, valve-in-ring, valve-in-MAC). Subsequently, we will discuss the anticipated benefits of TMVR with dedicated devices over TEER, summarize the characteristics and clinical results of TMVR systems currently under investigation, and outline future prospects in this field.

A review of potential mechanisms and uses of SGLT2 inhibitors in ischemia-reperfusion phenomena.

Recently added to the therapeutic arsenal against chronic heart failure as a first intention drug, the antidiabetic drug-class sodium-glucose cotransporter-2 inhibitors (SGLT2i) showed efficacy in decreasing overall mortality, hospitalization, and sudden death in patients of this very population, in whom chronic or acute ischemia count among the first cause. Remarkably, this benefit was observed independently from diabetic status, and benefited both preserved and altered ventricular ejection fraction. This feature, observed in several large randomized controlled trials, suggests additional effects from SGLT2i beyond isolated glycemia control. Indeed, both in-vitro and animal models suggest that inhibiting the Na+/H+ exchanger (NHE) may be key to preventing ischemia/ reperfusion injuries, and by extension may hold a similar role in ischemic damage control and ischemic preconditioning. Yet, several other mechanisms may be explored which may help better target those who may benefit most from SGLT2i molecules. Because of a large therapeutic margin with few adverse events, ease of prescription and potential pharmacological efficacity, SGLT2i could be candidate for wider indications. In this review, we aim to summarize all evidence which link SGLT2i and ischemia/reperfusion injuries modulation, by first listing known mechanisms, including metabolic switch, prevention of lethal arrythmias and others, which portend the latter, and second, hypothesize how the former may interact with these mechanisms.