Mitral regurgitation (MR) is associated with substantial morbidity and mortality. Within the past 15 years, mitral valve edge-to-edge repair (M-TEER) has developed from an experimental approach to a ...guideline-recommended, safe, and effective treatment option for patients with severe primary or secondary mitral regurgitation.
This review covered relevant publications of M-TEER and summarizes the development of M-TEER devices within the last 15 years. It outlines anatomical challenges which drove the evolution of M-TEER devices, provides an overview about the current state of clinical application and research, and offers an outlook into the future of transcatheter mitral valve treatment.
The development and refinement of new M-TEER device generations offer the possibility to treat a wide range of mitral valve anatomies. Choosing the best device for the individual anatomic properties of the patients and considering comorbidities is the key to maximized MR reduction, minimalized complication rates, and thus optimized postinterventional prognosis. Independent from prognostic implications, quality of life has become an important patient-centered outcome that can be improved by M-TEER in virtually all patients treated.
Atherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the ...pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with CHD and with carotid intima-media thickness (CIMT), as a surrogate measure of atherosclerosis.
The discovery phase included 1000 participants from the KORA F4 study, whose plasma protein levels were quantified using the aptamer-based SOMAscan proteomics platform. We evaluated the associations of plasma protein levels with CHD using logistic regression, and with CIMT using linear regression. For both outcomes we applied two models: an age-sex adjusted model, and a model additionally adjusted for body mass index, smoking status, physical activity, diabetes status, hypertension status, low density lipoprotein, high density lipoprotein, and triglyceride levels (fully-adjusted model). The replication phase included a matched case-control sample from the independent KORA F3 study, using ELISA-based measurements of galectin-4. Pathway analysis was performed with nominally associated proteins (p-value < 0.05) from the fully-adjusted model.
In the KORA F4 sample, after Bonferroni correction, we found CHD to be associated with five proteins using the age-sex adjusted model: galectin-4 (LGALS4), renin (REN), cathepsin H (CTSH), and coagulation factors X and Xa (F10). The fully-adjusted model yielded only the positive association of galectin-4 (OR = 1.58, 95% CI = 1.30-1.93), which was successfully replicated in the KORA F3 sample (OR = 1.40, 95% CI = 1.09-1.88). For CIMT, we found four proteins to be associated using the age-sex adjusted model namely: cytoplasmic protein NCK1 (NCK1), insulin-like growth factor-binding protein 2 (IGFBP2), growth hormone receptor (GHR), and GDNF family receptor alpha-1 (GFRA1). After assessing the fully-adjusted model, only NCK1 remained significant (β = 0.017, p-value = 1.39e-06). Upstream regulators of galectin-4 and NCK1 identified from pathway analysis were predicted to be involved in inflammation pathways.
Our proteome-wide association study identified galectin-4 to be associated with CHD and NCK1 to be associated with CIMT. Inflammatory pathways underlying the identified associations highlight the importance of inflammation in the development and progression of CHD.
Abstract
Background
Appropriate and timely anticoagulant therapy with vitamin K antagonists (VKAs) or non-vitamin K oral antagonists (NOACs) is essential for stroke prevention in non-valvular atrial ...fibrillation (NVAF). Comparative data regarding effectiveness and safety for edoxaban vs phenprocoumon, the predominant VKA in Germany, are scarce.
Objectives
The study evaluates effectiveness and safety of edoxaban vs phenprocoumon in NVAF patients in a German real-world setting.
Methods
German statutory health insurance claims data of the Institute for Applied Health Research Berlin (InGef) Research Database from 2014 until 2019 were analyzed. In NVAF patients, new users of edoxaban and phenprocoumon were compared to assess effectiveness (stroke/systemic embolism (SE)) and safety (bleeding) during therapy. Hazard ratios (HR) were estimated through multiple outcome-specific cox proportional hazard models adjusting for baseline characteristics. Outcomes of geriatric patients were analyzed in subgroup analyses.
Results
Between 2015 and 2018, 7,975 and 13,319 NVAF patients newly initiated treatment with edoxaban or phenprocoumon. After adjusting for baseline confounders, the risk of stroke/SE (HR: 0.85, 95% CI: 0.70–1.02) was numerically but not significantly lower, while the risk of major bleeding (HR: 0.69, 95% CI: 0.58–0.81) was significantly lower for edoxaban. In the geriatric subgroups, homogenous results compared to the main analysis were obtained.
Conclusion
The results of this real-world analysis indicated better effectiveness and safety outcomes in patients with NVAF initiating edoxaban treatment compared to phenprocoumon. The findings confirm that the beneficial effects observed in the pivotal ENGAGE AF-TMI 48 trial can also be achieved in real-world use of edoxaban.
Mitral valve transcatheter edge-to-edge repair (M-TEER) and replacement (TMVR) have evolved as guideline-recommended treatment approaches for mitral regurgitation (MR). Even though they are supported ...by a growing body of evidence from either randomized trials or large registries, there are still several unsolved challenges in the field of interventional MR treatment. In the present review, we discuss the ten most important open questions regarding M-TEER and TMVR.
Residual and recurrent mitral regurgitation after transcatheter edge-to-edge repair are therapeutically challenging. In the present case report, we describe a simplified, transapical electrosurgical ...laceration and stabilization of clip procedure that represents an alternative and direct approach for electrosurgical laceration of mitral valve leaflets enabling transcatheter mitral valve replacement for recurrent mitral regurgitation after mitral valve transcatheter edge-to-edge repair.
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Transcatheter tricuspid valve replacement (TTVR) is an increasingly used treatment technique for patients with severe tricuspid regurgitation (TR). Currently, available data from international ...registries and randomized controlled trials provide outcome data until a maximum follow-up of 2 years after the procedure. This case report presents 4-year follow-up data for an 84-year-old woman who underwent TTVR for torrential TR in 2019. The patient experienced durable TR reduction, symptomatic improvement, right ventricular reverse remodeling, and substantial improvement in liver and kidney function.
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Recordings of outward currents in human ventricular myocytes revealed the presence of a large calcium-insensitive transient outward current. This current has been suggested to contribute ...significantly to regional electrophysiological heterogeneity in myocardial cells and tissue of several animal species and to cause electrical gradients across the ventricular wall.
The patch-clamp technique was used to record action potentials and outward currents in myocytes enzymatically isolated from thin subepicardial and subendocardial layers of human nonfailing and failing left ventricle. In all subepicardial cells studied, a calcium-insensitive transient outward current (Ito1) could be recorded with large density (10.6 +/- 1.08 pA/pF at 40 mV), whereas current density of Ito1 in subendocardial cells was fourfold smaller (2.63 +/- 0.31 pA/pF, P<.0001, nonfailing myocardium). In failing hearts, the density of Ito1 was significantly smaller in subepicardial cells (7.81 +/- 0.53 pA/pF, P=.012) but not different in subendocardial myocytes (2.01 +/- 0.23 pA/pF, P=.25). Rate-dependent reduction of peak Ito1 at a 2-Hz depolarization rate was minimal in subepicardial cells (to 92.3 +/- 1.9%), whereas peak Ito1 in subendothelial myocytes was almost suppressed at 2 Hz (reduction to 13.2 +/- 2.1%, P<.0001). The different rate-dependent reduction of the transient outward current was due to a much slower time course of recovery from inactivation in subendocardial cells. Kinetic data, including action potentials recorded at 35 degree C, allow assessment of the role of the transient outward current for electrical activity and transmural voltage gradients in human left ventricle.
Marked regional differences in density and rate-dependent properties of the transient outward current exist in subendocardial and subepicardial layers in human left ventricular myocardium, causing transmural electrical gradients that are important for normal and pathological electrical behavior of the human heart. The difference in recovery rates of the transient outward current is a distinguishing feature between subepicardial and subendocardial myocytes.
Altered myocardial repolarization is one of the important substrates of ventricular tachycardia and fibrillation. The influence of rare gene variants on repolarization is evident in familial long QT ...syndrome. To investigate the influence of common gene variants on the QT interval we performed a linkage disequilibrium based SNP association study of four candidate genes. Using a two-step design we analyzed 174 SNPs from the KCNQ1, KCNH2, KCNE1, and KCNE2 genes in 689 individuals from the population-based KORA study and 14 SNPs with results suggestive of association in a confirmatory sample of 3277 individuals from the same survey. We detected association to a gene variant in intron 1 of the KCNQ1 gene (rs757092, +1.7 ms/allele, P=0.0002) and observed weaker association to a variant upstream of the KCNE1 gene (rs727957, +1.2 ms/allele, P=0.0051). In addition we detected association to two SNPs in the KCNH2 gene, the previously described K897T variant (rs1805123, -1.9 ms/allele, P=0.0006) and a gene variant that tags a different haplotype in the same block (rs3815459, +1.7 ms/allele, P=0.0004). The analysis of additive effects by an allelic score explained a 10.5 ms difference in corrected QT interval length between extreme score groups and 0.951 of trait variance (P<0.00005). These results confirm previous heritability studies indicating that repolarization is a complex trait with a significant heritable component and demonstrate that high-resolution SNP-mapping in large population samples can detect and fine map quantitative trait loci even if locus specific heritabilities are small.
Since transcatheter edge-to-edge repair (TEER) has become a valuable therapy in the treatment of both, mitral (MR) and tricuspid regurgitation (TR), the question of optimized patient selection has ...gained growing importance. After years of attributing rather little attention to the right ventricle (RV) and its function in the setting of valvular heart failure, this neglect has recently changed. The present review sought to summarize anatomy and function of the RV in a clinical context and aimed at presenting the current knowledge on how the RV influences outcomes after TEER for atrioventricular regurgitation. The anatomy of the RV is determined by its unique shape, which necessitates to use three-dimensional imaging methods for detailed and comprehensive characterization. Complex parameters such as RV to pulmonary artery coupling (RVPAc) have been developed to combine information of RV function and afterload which is primary determined by the pulmonary vasculature and LV filling pressure. Beyond that, TR, which is closely related to RV function also plays an important role in the setting of TEER. While mitral valve transcatheter edge-to-edge repair (M-TEER) leads to reduction of concomitant TR in some patients, the prognostic value of TR in the setting of M-TEER remains unclear. Overall, this review summarizes the current state of knowledge of the outstanding role of RV function and associated TR in the setting of TEER and outlines the unsolved questions associated with right-sided heart failure.
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