Applicazione clinica di una nuova tecnologia multielettrodica circolare per l'ablazione della fibrillazione atriale

Background: Continui sviluppi tecnologici interessano il campo dell’ablazione transcatetere della fibrillazione atriale (FA). Una nuova tecnologia circolare multielettrodica si presenta oggi come potenziale dispositivo per l’isolamento delle vene polmonari (VP) in pazienti con FA parossistica (FAP). Obiettivi: Abbiamo valutato la fattibilità, l’efficacia e la sicurezza della nuova tecnologia multielettrodica circolare nMARQ™ (Biosense Webster, Diamond Bar, USA) per il trattamento della FAP. Contestualmente sono stati confrontati i tempi di procedura e la quantità di liquidi somministrati al paziente per l’irrigazione del catetere in ablazione. Metodologia: Abbiamo incluso 30 pazienti consecutivi con indicazione all’ablazione transcatetere della FA che presentavano una diagnosi di FAP ed un’anatomia normale o minimamente alterata delle VP (4 VP o 4 osti separati), valutata tramite scansioni TC o RMN prima della procedura, in assenza di dilatazione dell’AS. Di questa popolazione un gruppo di 14 pazienti è stato indirizzato all’ablazione con sistema nMARQ™, i restanti 16 pazienti sono stati trattati con sistemi d’ablazione monoelettrodici di comune impiego presso il nostro centro (ThermoCool®/SmartTouch™). Risultati: Nel gruppo nMARQ™ tutte le VP (57) sono state correttamente isolate con un tempo di ablazione di 16 ± 6 min ed un numero di applicazioni di 31 ± 9. Abbiamo ottenuto una significativa riduzione del tempo totale di ablazione (p <0,0001) e del numero di applicazioni necessarie (p = 0,002), rispetto al gruppo di controllo. Non sono state riportate complicanze peri-procedurali. Il volume di liquidi infuso per l’irrigazione del catetere nMARQ™ in ablazione è risultato minore rispetto al controllo (p=0,0188). Conclusioni: L’impiego della nuova tecnologia multielettrodica circolare è risultato fattibile, con una massima efficacia nell’isolamento delle VP, una riduzione dei tempi di ablazione ed un profilo di sicurezza ottimale. Inoltre, è stata riportata una riduzione del volume di liquidi infusi al paziente per l’irrigazione del catetere in ablazione. Tali risultati necessitano di ulteriori studi e di valutazioni a lungo termine per poter essere confermati

Proarrhythmic effect of bipolar epicardial left ventricular stimulation in CRT resolved maintaining biventricular pacing with unipolar‐cathodical configuration: A peculiar case report

Abstract Background The effect of cardiac resynchronization therapy (CRT) on the risk of ventricular arrhythmias is controversial. Several studies reported a decreased risk, but some studies reported a potential proarrhythmic effect of epicardial left ventricular pacing resolved upon discontinuation of biventricular pacing (BiVp). Case Summary A 67‐year‐old woman with a history of heart failure due to nonischemic cardiomyopathy and left bundle branch block was hospitalized for CRT device implantation. Unpredictably, as soon as the leads have been connected to the generator, an electrical storm (ES) occurred with relapsing self‐resolving polymorphic ventricular tachycardia (PVT) triggered by ventricular extra beats with short‐long‐short sequences. The ES was resolved without interrupting BiVp switching to unipolar left ventricular (LV) pacing. This allowed to keep CRT active with extreme clinical benefit for the patient and to demonstrate that the cause of the PVT was the anodic capture of bipolar LV stimulation. Reverse electrical remodeling was also demonstrated after 3 months of effective BiVp. Discussion Proarrhythmic effect of CRT is a rare but significant complication of CRT, and it may compel to discontinuation of the BiVp. The reversal of the physiological transmural activation sequence of epicardial LV pacing and subsequent prolonging of corrected QT interval have been speculated as the most probable explanation, but our case highlights the possibility that the anodic capture may play a relevant role in PVT genesis

Update on Brugada Syndrome 2019

Brugada syndrome (BrS) was first described in 1992 as an aberrant pattern of ST segment elevation in right precordial leads with a high incidence of sudden cardiac death (SCD) in patients with structurally normal heart. It represents 4% ∼ 12% of all SCD and 20% of SCD in patients with structurally normal heart. The extremely wide genetic heterogeneity of BrS and other inherited cardiac disorders makes this new area of genetic arrhytmology a fascinating one. This review shows the state of art in diagnosis, management, and treatment of BrS focusing all the aspects regarding genetics and Preimplant Genetic Diagnosis (PGD) of embryos, overlapping syndromes, risk stratification, familial screening, and future perspectives. Moreover the review analyzes key points like electrocardiogram (ECG) criteria, the role of electrophysiological study (the role of ventricular programmed stimulation and the need of universal accepted protocol) and the importance of a correct risk stratification to clarify when implantable cardioverter defibrillator or a close follow–up is needed. In recent years, cardiovascular studies have been focused on personalized risk assessment and to determine the most optimal therapy for an individual. The BrS syndrome has also benefited of these advances although there remain several key points to be elucidated. We will review the present knowledge, progress made, and future research directions on BrS

Low-Dose bisphenol-A impairs adipogenesis and generates dysfunctional 3T3-L1 adipocytes

Environmental endocrine disruptors (EDCs), including bisphenol-A (BPA), have been recently involved in obesity and diabetes by dysregulating adipose tissue function. Our aim was to examine whether prolonged exposure to low doses of BPA could affect adipogenesis and adipocyte metabolic functions. Therefore, 3T3-L1 pre-adipocytes were cultured for three weeks with BPA 1 nM to mimic human environmental exposure. We evaluated BPA effect on cell proliferation, differentiation, gene expression and adipocyte metabolic function. BPA significantly increased pre-adipocyte proliferation (p<0.01). In 3T3-L1 adipocytes differentiated in the presence of BPA, the expression of Peroxisome proliferator-activated receptor gamma (PPARγ), Fatty Acid Binding Protein 4/Adipocyte Protein 2 (FABP4/AP2) and CCAAT/enhancer binding protein (C/EBPα) was increased by 3.5, 1.5 and 3 folds, respectively. Mature adipocytes also showed a significant increase in lipid accumulation (p<0.05) and alterations of insulin action, with significant reduction in insulin-stimulated glucose utilization (p<0.001). Moreover, in mature adipocytes, mRNA levels of Leptin, interleukin-6 (IL6) and interferon-γ (IFNγ) were significantly increased (p<0.05). In conclusion, BPA prolonged exposure at low doses, consistent with those found in the environment, may affect adipocyte differentiation program, enhancing pre-adipocyte proliferation and anticipating the expression of the master genes involved in lipid/glucose metabolism. The resulting adipocytes are hypertrophic, with impaired insulin signaling, reduced glucose utilization and increased pro-inflammatory cytokine expression. Thus, these data supported the hypothesis that BPA exposure, during critical stages of adipose tissue development, may cause adipocyte metabolic dysfunction and inflammation, thereby increasing the risk of developing obesity-related diseases

Low Dose Bisphenol-A Regulates Inflammatory Cytokines through GPR30 in Mammary Adipose Cells

The dramatic rise in obesity and metabolic syndrome can be related, at least in part, to environmental chemical factors such as Bisphenol-A (BPA). In this study, we aimed to understand the effects of low-dose Bisphenol-A on the human mature adipocytes and stromal vascular fraction (SVF) cells, obtained from subcutaneous mammary adipose tissue of overweight female patients, undergoing surgical mammary reduction. 24 and/or 48 hours exposure to BPA 0.1 nM elicited significant increase of the inflammatory molecules interleukin-6 (IL-6), interleukin-8 (IL-8), Monocyte chemo-attractant protein 1α (MCP1α) and induced G protein-coupled estrogen receptor 30 (GPR30) levels more than 2-fold both in mature adipocytes and SVF cells. These effects were similar to that obtained in presence of GPR30-specific agonist G1 (100 nM) and were reverted by G15 (1 µM), a GPR30-selective antagonist. As a result of BPA-GPR30 signaling activation, Fatty Acid Synthase (FAS) and leptin mRNA levels were significantly higher upon BPA exposure (p<0.05) in mature adipocytes, with an opposite effect on adiponectin (ADIPOQ). In addition, an increase in SVF cell proliferation and ERK1/2 phosphorylation, was observed, compared to untreated cells. G15 reverted all of these effects. Interestingly, the action of BPA on SVF cell growth was mimicked by IL-8 treatment and was reverted by incubation with anti-IL8 antibodies. All these data suggest that BPA at 0.1nM, a 10 times lower concentration than environmental exposure, increases the expression of pro-inflammatory cytokines via GPR30 both in mature mammary adipocytes and in SVF cells with a possible involvement of IL-8

BPA effect on insulin transduction pathway.

<p>Insulin signaling was tested in 3T3-L1 pre-adipocytes, before differentiation started (day 0; <b>A-C</b>) and in mature adipocytes (day 8; <b>B-D</b>). ERK1/2 (<b>A-B</b>) and PKB/AKT (<b>C-D</b>) phosphorylation after insulin stimulation were shown in untreated and BPA treated cells. Bars represent the mean ± SD of four independent experiments and blot is representative of four different experiments. Asterisks indicate statistically significant difference (*p<0.05, **p<0.01 and ***p<0.001) in adipocytes cultured upon BPA compared to controls.</p

BPA effect on cellular neutral lipid droplet accumulation and glucose utilization in 3T3-L1 mature adipocytes.

<p>The microphotographs were obtained with an optical microscope in two original magnifications (10X and 20X), following ORO staining <b>(A)</b> in adipocytes upon BPA incubation compared to control cells. Lipid quantification test <b>(B)</b> was expressed as optical density (OD). Insulin stimulated glucose utilization test, expressed as fold over basal, was shown in differentiated 3T3-L1 cells incubated with 1 nM of BPA <b>(C)</b>. Bars represent the mean ± SD of four independent experiments. Asterisks indicate statistically significant differences (*p<0.05 and ***p<0.001) between adipocytes cultured upon BPA compared to controls.</p

Effect of BPA on 3T3-L1 protein abundance of master differentiation genes.

<p>Protein levels of PPARγ <b>(A)</b>, FABP4/AP2 <b>(B)</b> and GLUT-4 <b>(C)</b> were assayed during adipogenesis at days 4 and 8 by western blot analysis, expressed as Arbitrary Unit (AU). Bars represent the mean ± SD of four independent experiments and blot is representative of four different experiments. Asterisks indicate statistically significant differences (*p<0.05) between days 4 and 8 for PPARγ <b>(A)</b> and day 8 for FABP4/AP2 <b>(B)</b>, without and with BPA incubation, both compared to untreated day 4. Hash (#p<0.05) expresses statistically significant differences between days 4 and 8 for PPARγ <b>(A)</b> and day 8 for FABP4/AP2 <b>(B)</b>, upon BPA incubation compared to controls. No significant differences in GLUT-4 protein expression <b>(C)</b>.</p

Pro-inflammatory effect in 3T3-L1 mature adipocytes.

<p>In mature adipocytes, mRNA levels of Leptin <b>(A)</b>, IL6 <b>(B)</b>, IFNγ <b>(C)</b>, TNFα <b>(D)</b> and adiponectin <b>(E)</b> were assayed at day 8, the end of adipogenesis, by Real-time RT-PCR analysis, and expressed as Relative Expression Unit (REU). Bars represent the mean ± SD of four independent experiments. Asterisk indicates statistically significant difference (*p<0.05) between adipocytes cultured upon BPA treatment compared to controls.</p