Atherosclerosis rarely develops in the region of arteries exposed to undisturbed flow (u-flow, unidirectional flow). Instead, atherogenesis occurs in the area exposed to disturbed flow (d-flow, multidirectional flow). Based on these general pathohistological observations, u-flow is considered to be atheroprotective, while d-flow is atherogenic. The fact that u-flow and d-flow induce such clearly different biological responses in the wall of large arteries indicates that these two types of flow activate each distinct intracellular signaling cascade in vascular endothelial cells (ECs), which are directly exposed to blood flow. The ability of ECs to differentially respond to the two types of flow provides an opportunity to identify molecular events that lead to endothelial dysfunction and atherosclerosis. In this review, we will focus on various molecular events, which are differentially regulated by these two flow types. We will discuss how various kinases, ER stress, inflammasome, SUMOylation, and DNA methylation play roles in the differential flow response, endothelial dysfunction, and atherosclerosis. We will also discuss the interplay among the molecular events and how they coordinately regulate flow-dependent signaling and cellular responses. It is hoped that clear understanding of the way how the two flow types beget each unique phenotype in ECs will lead us to possible points of intervention against endothelial dysfunction and cardiovascular diseases.

SUMOylation, a reversible post-transcriptional modification process, of proteins are involved in cellular differentiation, growth, and even motility by regulating various protein functions. SUMOylation is not limited to cytosolic proteins as recent evidence shows that nuclear proteins, those associated with membranes, and mitochondrial proteins are also SUMOylated. Moreover, it is now known that SUMOylation plays an important role in the process of major human ailments such as malignant, cardiovascular and neurological diseases. In this chapter, we will highlight and discuss how the localization of SUMO protease and SUMO E3 ligase in different compartments within a cell regulates biological processes that depend on SUMOylation. First, we will discuss the key role of SUMOylation in the nucleus, which leads to the development of endothelial dysfunction and atherosclerosis. We will then discuss how SUMOylation of plasma membrane potassium channel proteins are involved in epilepsy and arrhythmia. Mitochondrial proteins are known to be also SUMOylated, and the importance of dynamic-related protein 1 (DRP1) SUMOylation on mitochondrial function will be discussed. As we will emphasize throughout this review, SUMOylation plays crucial roles in different cellular compartments, which is coordinately regulated by the translocation of various SUMO proteases and SUMO E3 ligase. Comprehensive approach will be necessary to understand the molecular mechanism for efficiently moving around various enzymes that regulate SUMOylation within cells.

Objective. To assess 1-year mortality after transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic stenosis (AS). Background. Clinical trials have proven the beneficial effect of TAVR on mortality in patients with tricuspid AS. Individuals with bicuspid AS were excluded from these trials. Methods. A meta-analysis using literature search from the Cochrane, PubMed, ClinicalTrials, SCOPUS, and EMBASE databases was conducted to determine the effect of TAVR on 1-year mortality in patients with bicuspid AS. Short-term outcomes that could potentially impact one-year mortality were analyzed. Results. After evaluating 380 potential articles, 5 observational studies were selected. A total of 3890 patients treated with TAVR were included: 721 had bicuspid and 3,169 had tricuspid AS. No statistically significant difference between the baseline characteristics of the two groups of patients was seen outside of mean aortic gradient. Our primary endpoint of one-year all-cause mortality revealed 85 deaths in 719 patients (11.82%) with bicuspid AS compared to 467 deaths in 3100 patients (15.06%) with tricuspid AS, with no difference between both groups [relative risk (RR) 1.03; 95% CI 0.70-1.51]. Patients with bicuspid AS were associated with a decrease in device success (RR 0.62; 95% CI 0.45-0.84) and an increase in moderate-to-severe prosthetic valve regurgitation (RR 1.55; 95% CI 1.07-2.22) after TAVR compared to patients with tricuspid AS. The effect of meta-regression coefficients on one-year all-cause mortality was not statistically significant for any patient baseline characteristics. Conclusion. When comparing TAVR procedure in tricuspid AS versus bicuspid AS, there was no difference noted in one-year all-cause mortality.

No abstract

Multiple clinical trials have demonstrated the efficacy of implantable cardioverter-defibrillators (ICDs) for the prevention of sudden cardiac death (SCD) among specific high-risk populations. However, it remains unclear how to optimally treat those patients who are at elevated risk of cardiac arrest but are not among the presently identified groups proven to benefit from an ICD, are unable to tolerate surgical device implantation, or refuse invasive therapies. The wearable cardioverter-defibrillator (WCD) is an alternative antiarrhythmic device that provides continuous cardiac monitoring and defibrillation capabilities through a noninvasive, electrode-based system. The WCD has been shown to be highly effective at restoration of sinus rhythm in patients with a ventricular tachyarrhythmia, and one randomized trial using the WCD in patients with recent myocardial infarction at elevated risk for arrhythmic death reported a decrease in overall mortality despite no SCD mortality benefit. The current clinical indications for WCD use are varied and continue to evolve as experience with this technology increases.

No abstract

No abstract

Background Ventricular arrhythmias (VAs) and their treatment have been associated with psychological distress and diminished quality of life (QOL). We administered a battery of patient‐reported outcome measures (PROMs) to patients seeing an electrophysiologist and psychologist in a multidisciplinary VA clinic for patients referred for consideration of catheter ablation for sustained VAs or implantable cardioverter‐defibrillator therapies. Methods and Results In this retrospective study of the initial VA clinic visit, we analyzed PROMs of: anxiety and depression symptoms, visual analog scales for physical health status and quality of life, cardiac anxiety, implantable cardioverter‐defibrillator acceptance, and implantable cardioverter‐defibrillator shock anxiety. We quantitated baseline PROM score means and performed correlation analysis with clinical makers of cardiac and VA disease severity. We also performed an item‐level analysis of each PROM question to quantify most frequent patient concerns. A total of 66 patients (56±15 years; 77% men) were included; 70% had prior implantable cardioverter‐defibrillator shock, and 44% with prior VA ablation. Elevated symptoms of anxiety (53%) and depression (20%) were common. Younger patients had greater symptom burden of general health anxiety, cardiac anxiety, and shock anxiety, and lower device acceptance, but indices of VA burden such as number of ICD shocks and time since last ICD shock did not predict anxiety or depression. Item‐level review of cardiac‐specific PROMs revealed that >40% of patients expressed concern regarding resumption of physical activity, sex and employment. Conclusions Clinicians can expect elevated symptoms of depression, and cardiac and device‐related anxiety among patients with VAs. Routine use of PROMs may elicit these symptoms, which were otherwise not predicted by arrhythmia burden.  Review of individual PROM items can facilitate targeting specific patient concerns, which commonly involved physical activity.