Minimally Invasive Approaches to Mitral Valve Surgery: Where Are We Now? A Narrative Review.

Minimally invasive mitral valve surgery (MiMVS) has been increasing in prevalence. This review will focus on the approaches, the clinical outcomes, and patient selection for MiMVS. There are four minimally invasive approaches to the mitral valve: Right mini-thoracotomy, both video-assisted and fully endoscopic, robotic mitral surgery, and transapical, beating heart off-pump neochordal repair. Advantages over conventional surgery include less blood loss and transfusion, improved postoperative mobility, shorter length of stay, less postoperative atrial fibrillation, fewer surgical site infections, and improved cosmesis. This range of minimally invasive techniques will continue to evolve, providing options that are tailored for different patient populations.

Surgical vs transcatheter aortic valve replacement in bicuspid aortic valve stenosis: A systematic review and meta-analysis.

This systematic review and meta-analysis aim to provide a comprehensive analysis of the literature directly comparing the outcomes of surgical aortic valve replacement (SAVR) and TAVR in patients with BAV stenosis. Medline, PubMed, and Scopus were systematically searched for articles published between 2000 and 2023, 1862 studies were screened, and 6 retrospective studies met the inclusion criteria. We included 6550 patients in the final analyses: 3,292 and 3,258 in the SAVR and TAVR groups, respectively. Both groups have similar rates of in-hospital mortality (odds ratio (OR) 1.11; 95% CI 0.59-2.10; p = 0.75) and stroke (OR 1.25; 95% CI 0.85-1.86; p = 0.26. Patients who underwent SAVR experienced lower rates of permanent pacemaker implantation (OR 0.54; 95% CI 0.35-0.83; p = 0.005) and paravalvular leak (OR 0.47; 95% CI 0.26-0.86; p = 0.02). On the other hand, patients who underwent TAVR displayed lower rates of acute kidney injury (OR 1.81; 95% CI 1.15-2.84; p = 0.010), major bleeding (OR 3.76; 95% CI 2.18-6.49; p < 0.00001), and pulmonary complications (OR 7.68; 95% CI 1.21-48.84; p = 0.03). Despite the early mortality data suggesting that TAVR may be a reasonable strategy for patients with bicuspid AS with low to intermediate surgical risk, the increased risk of PPI and PVL is concerning. A prospective, randomized, controlled trial reporting long-term outcomes with pre-defined subgroup analyses based on BAV morphology is paramount. In the interim, caution should be exercised in the widespread adoption of TAVR in lower surgical-risk patients.

Effect of glucagon-like peptide-1 receptor agonists administration during coronary artery bypass grafting: a systematic review and meta-analysis of randomized control trials.

Aim: To determine if glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can benefit patients receiving coronary artery bypass graft (CABG), GLP-1 RAs administration alongside standard insulin was compared with perioperative insulin alone. Materials & methods: All articles from Pubmed and Scopus databases that compared GLP-1 RA administration to insulin alone during CABG were included for meta-analysis. Short-term postoperative outcomes were analyzed between groups. Results: Average postoperative blood glucose levels significantly favored GLP-1 RA with a mean difference of -0.72 (p < 0.001). No other variables were significantly different between GLP-1 RA and insulin alone. Conclusion: GLP-1 RA is a safe option for perioperative care of CABG patients that can potentially improve postoperative outcomes of CABG patients by improving glycemic control and reducing hyperglycemic episodes.

What is this article about? Coronary artery bypass graft (CABG) is a common surgery for patients who have blocked blood vessels in their heart preventing their heart from functioning properly. Compared with other treatment options, CABG has better long-term outcomes and chances of survival, especially for patients with diabetes. Some medications that lower blood sugar levels in patients with diabetes, are also well known to improve heart health in this population. Because of these benefits, the specific medication called GLP-1 RA, has been proposed as an option to improve outcomes of people receiving CABG surgery. What were the results? By taking a systematic approach, 1375 articles were screened to find seven trials that tested the comparison of GLP-1 RA versus a control of just insulin in CABG patients. Analyzing this data, CABG patients receiving GLP-1 RA had significantly lower blood sugar levels compared with patients getting the control. The GLP-1 RA group also, on average, had similar or lower levels of heart rate arrhythmias, events of critically low blood sugar and the need of serious interventions compared with the control group. What do the results of the study mean? These results demonstrate that GLP-1 RA have similar or improved outcomes compared with standard therapy alone, suggesting it as a safe option for CABG patients. By lowering blood sugar levels, GLP-1 RA could also decrease complication rates and improve patient management compared with standard therapy alone, since high blood sugar levels are correlated with increased complications and worse postoperation outcomes.

Mortality and morbidity of surgical and transcatheter mitral valve repair in octogenarians: A systematic review.

BACKGROUND: Valvular heart disease (VHD) is a prominent problem in healthcare today with mitral regurgitation (MR) being the leading cause of VHD in the elderly population. While mitral valve repair (MVr) surgery is one of the only options for the end-stage disease, octogenarians are often denied MVr due to concerns with operative mortality and postoperative morbidity. To provide information on this underrepresented group of surgical patients, a systematic approach was taken to review the mortality and morbidity rates of octogenarians who received MVr. METHODS: Pubmed and Medline were searched for articles containing outcomes of octogenarians receiving surgical mitral valve repair (SMVr) or transcatheter mitral valve repair (TMVr) published after 2000. Ten articles met the inclusion criteria for a total of 7968 patients included in the analysis using Microsoft Excel, Version 2105. RESULTS: Short-term mortality rates for SMVr and TMVr were 2.6% and 1.4% for in-hospital, and 7.8% and 3.3% for 30 days, respectively. The average incidence of stroke, acute kidney injury, infection, and major bleeding for SMVr were 3.2%, 11.2%, 7.7%, and 24%, respectively, and 0.3%, 6.7%, 2.7%, and 7.9% for TMVr, respectively. CONCLUSION: Octogenarians receiving SMVr or TMVr experienced similar rates of short-term mortality and morbidity as younger populations, and when considering life expectancy, midterm mortality was also similar. With these results, denying octogenarians MVr operations based on age alone should be reconsidered. Depending on risk factors and comorbidities, either SMVr or TMVr is a viable and relatively safe option for octogenarians with severe MR.

Cannabidiol inhibits the skeletal muscle Nav1.4 by blocking its pore and by altering membrane elasticity.

Cannabidiol (CBD) is the primary nonpsychotropic phytocannabinoid found in Cannabis sativa, which has been proposed to be therapeutic against many conditions, including muscle spasms. Among its putative targets are voltage-gated sodium channels (Navs), which have been implicated in many conditions. We investigated the effects of CBD on Nav1.4, the skeletal muscle Nav subtype. We explored direct effects, involving physical block of the Nav pore, as well as indirect effects, involving modulation of membrane elasticity that contributes to Nav inhibition. MD simulations revealed CBD's localization inside the membrane and effects on bilayer properties. Nuclear magnetic resonance (NMR) confirmed these results, showing CBD localizing below membrane headgroups. To determine the functional implications of these findings, we used a gramicidin-based fluorescence assay to show that CBD alters membrane elasticity or thickness, which could alter Nav function through bilayer-mediated regulation. Site-directed mutagenesis in the vicinity of the Nav1.4 pore revealed that removing the local anesthetic binding site with F1586A reduces the block of INa by CBD. Altering the fenestrations in the bilayer-spanning domain with Nav1.4-WWWW blocked CBD access from the membrane into the Nav1.4 pore (as judged by MD). The stabilization of inactivation, however, persisted in WWWW, which we ascribe to CBD-induced changes in membrane elasticity. To investigate the potential therapeutic value of CBD against Nav1.4 channelopathies, we used a pathogenic Nav1.4 variant, P1158S, which causes myotonia and periodic paralysis. CBD reduces excitability in both wild-type and the P1158S variant. Our in vitro and in silico results suggest that CBD may have therapeutic value against Nav1.4 hyperexcitability.

E1784K, the most common Brugada syndrome and long-QT syndrome type 3 mutant, disrupts sodium channel inactivation through two separate mechanisms.

Inheritable and de novo variants in the cardiac voltage-gated sodium channel, Nav1.5, are responsible for both long-QT syndrome type 3 (LQT3) and Brugada syndrome type 1 (BrS1). Interestingly, a subset of Nav1.5 variants can cause both LQT3 and BrS1. Many of these variants are found in channel structures that form the channel fast inactivation machinery, altering the rate, voltage dependence, and completeness of the fast inactivation process. We used a series of mutants at position 1784 to show that the most common inheritable Nav1.5 variant, E1784K, alters fast inactivation through two separable mechanisms: (1) a charge-dependent interaction that increases the noninactivating current characteristic of E1784K; and (2) a hyperpolarized voltage dependence and accelerated rate of fast inactivation that decreases the peak sodium current. Using a homology model built on the NavPaS structure, we find that the charge-dependent interaction is between E1784 and K1493 in the DIII-DIV linker of the channel, five residues downstream of the putative inactivation gate. This interaction can be disrupted by a positive charge at position 1784 and rescued with the K1493E/E1784K double mutant that abolishes the noninactivating current. However, the double mutant does not restore either the voltage dependence or rates of fast inactivation. Conversely, a mutant at the bottom of DIVS4, K1641D, causes a hyperpolarizing shift in the voltage dependence of fast inactivation and accelerates the rate of fast inactivation without causing an increase in noninactivating current. These findings provide novel mechanistic insights into how the most common inheritable arrhythmogenic mixed syndrome variant, E1784K, simultaneously decreases transient sodium currents and increases noninactivating currents, leading to both BrS1 and LQT3.

Cannabinoid interactions with ion channels and receptors.

Cannabidiol (CBD), the non-psychoactive component of Cannabis sativa, acts on a diverse selection of membrane proteins with promising therapeutic potential in epilepsy and chronic pain. One such protein is the voltage-gated sodium channel (Nav). CBD shows a lack of specificity for sodium channels; however, the method of interaction is still unknown. In this review, we will outline the studies that report reproducible results of CBD and other cannabinoids changing membrane channel function, with particular interest on Nav. Nav are implicated in fatal forms of epilepsy and are also associated with chronic pain. This makes Nav potential targets for CBD interaction since it has been reported to reduce pain and seizures. One potential method of interaction that is of interest in this review is whether CBD affects channel function by altering lipid bilayer properties, independent of any possible direct interaction with membrane channels. CBD's ability to interact with its targets is a novel and important discovery. This discovery will not only prompt further research towards CBD's characterization, but also promotes the application of cannabinoids as potentially therapeutic compounds for diseases like epilepsy and pain.