Chronic Exposure to High Doses of Bisphenol A Exhibits Significant Atrial Proarrhythmic Effects in Healthy Adult Rats

Objectives: We aimed to evaluate the effects of chronic exposure to bisphenol A (BPA) on atrial fibrillation (AF) occurrence in rats. Methods: Twenty-two healthy female Wistar rats were randomized into three groups: Control (no BPA; n=7), BPA (exposed to usual BPA doses; 50 μg/kg/day, 9 weeks; n=7), and hBPA (exposed to high BPA doses; 25 mg/kg/day, 9 weeks; n=8). 24-h ECG monitoring was performed using radiotelemetry ECG devices prior to and after transesophageal atrial pacing. Spontaneous and pacing-induced atrial arrhythmias, autonomic tone, and in vivo an in vitro atrial arrhythmogenicity-related parameters were evaluated. Results: All studied parameters were similar between Control and BPA (all p>0.05). However, compared to Control, hBPA presented more atrial premature beats both at baseline (p=0.04) and after pacing (p=0.03), more AF episodes (p<0.001) and of longer duration (p=0.02) following transesophageal stimulation, and significantly higher vagal tone (all p<0.05). Conclusions: Chronic exposure to high, but not usual BPA doses induced significant atrial proarrhythmic effects in healthy rats, and this may be at least partially due to BPA-induced vagal hyperactivation. Exposure to high BPA doses, such as that occurring in plastics industry workers, could favor AF occurrence even in the absence of underlying cardiovascular disease.

Role of Preexisting Proarrhythmic Atrial Remodeling in Post-Coronary Artery Bypass Grafting Atrial Fibrillation

Introduction: Due to its deleterious effects, early identifi cation of patients at risk of postoperative AF (POAF) is of critical importance. Preexisting proarrhythmic atrial remodeling could contribute to this increased risk. Therefore, we aimed to evaluate the presence of preexisting proarrhythmic atrial remodeling and its impact on POAF occurrence in patients undergoing coronary artery bypass grafting (CABG). Methods: Data regarding atrial structural (atrial size and histology), electrical (P-wave and atrial action potential parameters, mRNA expression of several AF-related genes), and autonomic (heart rate variability parameters) proarrhythmic remodeling were compared between patients with (AF; n=11) and without (no-AF; n=19) POAF. Impact of POAF on postoperative outcomes was also evaluated. Results: No signifi cant difference was observed in atrial electrical parameters between the two groups (all p>0.05). However, compared with no-AF, AF patients had more important subepicardial adipose infi ltration (p=0.02) and higher markers of parasympathetic and sympathetic modulation (both p=0.03). Patients with POAF had longer hospital stay and more often presented postoperative renal dysfunction (both p=0.04). Conclusion: These fi ndings suggest that preexisting atrial structural (i.e., increased atrial subepicardial adiposity) and autonomic (i.e., sympatho-vagal coactivation) alterations could favor the occurrence of POAF. At its turn, POAF was associated with altered postoperative outcomes in CABG patients.

The Workload of the Interventional Cardiology Centers from Romania: a 2020 Overview and 2014-2020 Trends

This article provides data of the workload of the interventional cardiology centers from Romania during 2020. Members from all interventional cardiology centers from Romania wererequested to fill a standard form about the total number of various procedures performed during 2020. The report highlights the total number of coronary interventions, peripheral interventions, and interventions for structural heart diseases, that were performed in 2020 in Romania. A comparison of the workload of the interventional cardiology centers from Romania between 2014 to 2020 was done.

Correlation between Heart Rate Variability and Claustrum Stimulation – Hypothesis, Experimental Studies and Future Perspectives

Heart rate variability (HRV) has long been associated with cardiovascular risk, especially after a myocardial infarction, but also in general. HRV refl ects and is used as a surrogate for the balance between sympathetic and parasympathetic systems in modulating the cardiovascular activity. A low HRV, traditionally associated to sympathovagal imbalance, is associated with a worse cardiovascular prognosis. Deep brain stimulation (DBS) is a surgical technique used for severe cases of Parkinson’s disease and other neurologic pathologies. DBS is performed in various areas of the brain and through different protocols. The claustrum, an area located between the external capsule and the insular cortex, was recently shown to be connected to Parkinson’s motor symptoms. As DBS in other regions of the brain has proven non-motor effects, like infl uencing the HRV, we sought to document the effect of claustrum stimulation on the sympatho-vagal balance (SVB). Our preliminary data indicates that claustrum stimulation inclines the SVB toward the latter, but more studies are required to observe the long-term effects of this type of stimulation.

Studying the Innate Immune Response to Myocardial Infarction in a Highly Efficient Experimental Animal Model

The reduction in mortality following acute myocardial infarction (AMI) is an important achievement of modern medicine. Despite this progress, AMI remains the most common cause of heart failure (HF) and HF-related morbidity and mortality. The involvement of the innate immune response in different stages after AMI has at tracted important attention in recent years. With the increasing range of potential therapeutic compounds and delivery vectors, the need of highly efficient experimental AMI models is increasing, to support further advancement in this field. Here, we present a high-throughput model for the assessment of the innate immune response to AMI. The model is based on permanent surgical ligation of the left descending coronary artery (LAD) in mice, followed by complex flow-cytometry and histological analyses of immune cellular populations in blood and myocardium. We are presenting time-dependent qualitative and quantitative analysis results, demonstrating intense accumulation of Ly6Ghi neutrophils and Ly6Chi monocytes in the infarcted myocardium on days 1 and 3 post-AMI, followed by successive accumulation of reparatory Ly6CloMerTKhi macrophages, neovascularization and fibrosis development by day 7.

A Case of Enterococcus Spp. Endocarditis in a Seemingly Cured Hemorrhoidal Disease. Case Report

Background: Infective endocarditis with Enterococcus spp. is common in patients with digestive tract diseases. Such patients should be monitored periodically through clinical examination and colonoscopy, to detect the recurrence of seemingly cured disease. There are currently no studies on the incidence of infective endocarditis in patients with hemorrhoidal disease. Case report: The case of a 48-year-old man is addressed, known with type 2 diabetes mellitus, with a seemingly cured hemorrhoidal disease, who developed infective endocarditis of the mitral and aortic valve, complicated by ischemic stroke as the fi rst symptom. After six weeks of antibiotic treatment, an almost complete echocardiographic resolution of the vegetation was achieved, such that surgical intervention was postponed. Conclusion: Performing a colonoscopy in all Enterococcus spp. infective endocarditis patients, regardless of the presumed source of infection, could be helpful in diagnosing colorectal disease and avoiding a new bacteraemia episode - and eventually infective endocarditis - by the same or a different microorganism. The presented case emphasizes the importance of periodic monitoring of the digestive tract for hemorrhoidal disease in patients with a high risk of recurrence - due to high risk of bacteraemia and systemic complications. Moreover, it is worth noting that in certain cases, efficient antibiotic treatment on its own can achieve an outstanding result for patients with large vegetations, presenting with an embolic episode, and thus postpone (indefinitely) a surgical intervention.

Developing the Tissue Engineered Heart Valve – a Descriptive Hemodynamic and Ultrasound in Vitro Characterization Study of Heart Valves in a Bioreactor

The inherent limitations of current heart valve substitutes create the premise for the Tissue Engineered Heart Valve (TEHV), considered the perfect substitute. We aimed to compare in vitro hemodynamic performances of our TEHV, the conventional prosthetic valve and similar porcine valves, by ultrasonography and geometry resulting in six valve models analysis. In a bioreactor, pulmonary and aortic physiology were replicated thus hemodynamic characteristics were tested. Using ultrasound, transvalvular pressure gradients and flow were measured and used to calculate their valvular functional area (VFA) and using a high-speed camera, the geometric peak opening area (GOA) was assessed. The obtained results were normalized to the diameter of the biological prosthesis in order to increase the measurement’s accuracy. The ultrasound revealed normal function of all valves and physiologic transvalvular pressure gradients. The TEHV scaffold revealed absence of laceration or dehiscence, and performances in accordance with the control prostheses. The GOA was facile to obtain and the normalized values proved to be greater than the calculated functional area in all analyzed cases and the peak opening areas resulted lesser for the aortic conditions for all six used valves prototypes. To our knowledge, this is the first study to use bioreactors, for in vitro evaluation of heart valves.

Cardiac Contractility Modulation Therapy for Heart Failure – First Romanian Experience

Aim: The purpose of this study is to present the first Romanian case-series of patients with heart failure with reduced ejection fraction (HFrEF), supported with the newest generation of cardiac contractility modulation (CCM) device. Methods and results: 16 patients (15 men), aged 66.6±7.49 years, were supported with OPTIMIZER® smart IPG CCMX10 device and followed-up for an average duration of 385.75±326.32 days. The etiology of HF was ischemic in 13 patients (81%), 8 patients (50%) had atrial fibrillation, mean creatinine clearance value was 55.8±13.87 ml/min, and 5 patients (31,2%) had diabetes mellitus. All patients were supported with an implanted cardio verter-defibrillator (ICD), while 5 patients (31.2%) had cardiac resynchronization therapy (CRT) on top. The pharma cological treatment has been optimized in all patients. Six months after implantation, the LVEF has increased from 25.93%±6.21 to 35.5%±4.31 (p=0.00002), NYHA class improved from 3.18±0.4 to 1.83±0.38 (p<0.0001), and exercise tolerance evaluated with 6 minute walking test (6MWT) increased (from 321.87±70.63m to 521.41±86.43m; p<0,00001). Three patients (18,7%) died during the follow-up period after 48, 108 and 545 days (one non-cardiac death). Conclusions: Cardiac contractile therapy is a feasible, safe, and useful therapy for patients with HFrEF whose symptomatology is not improved with optimal standard therapy.

In Silico Analysis of Novel Titin Non-Synonymous Missense Variants Detected by Targeted Next Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy

Background and aim: Most of detected variants in cardiogenetic panels are still classified as variants of unknown significance, requiring supplementary analyses for a defi nite classifi cation. Performing further in-depth studies on such vast number of candidates is unfeasible. We sought to prioritise the novel nonsynonymous missense variants identified in titin gene (TTN) in a cohort of Romanian index cases with hypertrophic cardiomyopathy (HCM). Methods: 45 unrelated probands with HCM were screened by targeted next generation sequencing (NGS) covering all TTN exons. A stepwise strategy was used to select and prioritize the candidate variants for subsequent investigation. Results: Using rigorous bioinformatic filtering, 7 novel TTN nonsynonymous missense variants were identified and were the subject of in silico sequential analysis. 4 of the 7 variants were predicted to be possibly pathogenic by the Mendelian Clinically Applicable Pathogenicity (M-CAP) algorithm. Of these, three sequence variants (c.30392G>T, c.2518G>T, and c.49G>T) were also predicted to be destabilizing according to the second computational tool (TITINdb) and were designated as likely function-impacting. Conclusions: Herein we presented our strategy to hand-pick the novel TTN missense variants to be considered for further experimental studies. By applying various in silico tools, we restricted the list of sequence variants to be investigated to those most likely to be disease-associated, and thus reducing the need to perform expensive and time-consuming additional studies.