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The impact of sex in clinical and procedural outcomes in leadless pacemaker (LPM) patients has not yet been investigated. The purpose of this study was to investigate sex-related differences in patients undergoing LPM implantation. Consecutive patients enrolled in the i-LEAPER registry were analyzed. Comparisons between sexes were performed within the overall cohort using an adjusted analysis with 1:1 propensity matching for age and comorbidities. The primary outcome was the comparison of major complication rates. Sex-related differences regarding electrical performance and all-cause mortality during follow-up were deemed secondary outcomes. In the overall population (n = 1179 patients; median age 80 years), 64.3% were men. After propensity matching, 738 patients with no significant baseline differences among groups were identified. During median follow-up of 25 [interquartile range 24–39] months, female sex was not associated with LPM-related major complications (hazard ratio [HR] 2.03; 95% confidence interval [CI] 0.70–5.84; P =.190) or all-cause mortality (HR 0.98; 95% CI 0.40–2.42; P =.960). LPM electrical performance results were comparable between groups, except for a higher pacing impedance in women at implant and during follow-up (24 months: 670 [550–800] Ω vs 616 [530–770] Ω; P =.014) that remained within normal limits. In a real-world setting, we found differences in sex-related referral patterns for LPM implantation with an underrepresentation of women, although major complication rate and LPM performance were comparable between sexes. Female patients showed higher impedance values, which had no impact on overall device performance. Electrical parameters remained within normal limits in both groups during the entire follow-up. [ABSTRACT FROM AUTHOR]

• Emphasizing patient preferences and improving communication between HCPs and patients is needed. • Adoption of holistic, evidence-based approaches to MS management, including psychological support and exercise, is warranted. • There is a need for more diverse research methods in assessing patient preferences in MS Multiple sclerosis (MS) is a chronic inflammatory disorder affecting the brain and spinal cord, characterized by immune-mediated myelin damage. Early intervention and detection programs have emerged as promising strategies to improve patient outcomes by identifying and treating MS in its earliest stages. This systematic literature review aims to provide an overview of the preferences, attitudes, and opinions of both patients and healthcare professionals regarding early intervention or early detection programs for MS. A comprehensive search strategy was employed in March 2023 across multiple databases (MEDLINE, Scopus, PsyInfo, PubMed), from 1990 to 2023. A total of 38 articles were selected for analysis based on predefined inclusion and exclusion criteria. The majority of articles were published in recent years and represented different methods from case reports to randomized controlled trials, with fewer systematic literature reviews. Data collection approaches included patients, healthcare workers, or mixed samples with varying age ranges and gender ratios, frequently preferring women. These samples represented different preference study methods. The included studies were primarily conducted in the USA and the UK. Thematic analysis revealed several key themes : 1) differences emerged between healthcare professionals' and patients' perspectives 2) interventions for MS outside Disease-Modifying Therapies (DMTs) 3) severe side effects 4) communication, information, and knowledge 5) psychological and emotional aspects. Understanding these diverse factors and subgroups within the MS population can inform more effective, personalized approaches to MS prevention and treatment. [ABSTRACT FROM AUTHOR]

Elevated resting heart rate is a risk factor for cardiovascular events. The purpose of this study was to investigate the clinical significance of nocturnal heart rate (nHR) and 24-hour mean heart rate (24h-HR) obtained by continuous remote monitoring (RM) of implantable devices. We analyzed daily-sampled trends of nHR, 24h-HR, and physical activity in patients on β-blocker therapy for chronic heart failure and with implantable cardioverter-defibrillators or cardiac resynchronization therapy defibrillators (CRT-Ds). Patients were grouped by average nHR and 24h-HR quartile during follow-up to estimate the respective incidence of nonarrhythmic death and device-treated ventricular tachycardia/fibrillation (VT/VF). The study cohort included 1330 patients (median age 69 years [interquartile range 61–77 years]; 41% [n = 550] with CRT-D; median follow-up 25 months [interquartile range 13–42 months]). Compared with patients in the lowest nHR quartile (≤57 beats/min) group, patients in the highest quartile group (>65 beats/min) had an increased risk of nonarrhythmic death (adjusted hazard ratio [AHR] 2.25; 95% confidence interval [CI] 1.13–4.50; P =.021) and VT/VF (AHR 1.98; 95% CI 1.40–2.79; P <.001) and were characterized by the lowest level of physical activity (P ≤.0004 vs every other nHR quartiles). The highest 24h-HR quartile group (>75 beats/min) showed an increased risk of VT/VF (AHR 2.13; 95% CI 1.52–2.99; P <.001) and a weaker though significant association with nonarrhythmic mortality (AHR 1.80; 95% CI 1.00–3.22; P =.05) as compared with the lowest 24h-HR quartile group (≤65 beats/min). In remotely monitored patients with implantable cardioverter-defibrillator/CRT-D on β-blocker therapy for heart failure, elevated heart rates (nHR >65 beats/min and 24h-HR >75 beats/min) were associated with increased mortality and VT/VF risk. nHR showed a stronger association than 24h-HR with worst prognosis and lowest physical activity. [ABSTRACT FROM AUTHOR]

Background: Abnormal ventricular signals (AVS) are the cornerstone of substrate-based ventricular tachycardia (VT) ablation in sinus rhythm. Signal characterization of AVS in ischemic and nonischemic cardiomyopathies has never been performed.Objective: The purpose of this study was to describe ventricular signal abnormalities in 3 different pathologies and examine their association with the diastolic component of VT circuits.Methods: A total of 45 patients (15 ischemic cardiomyopathy [ICM], 15 arrhythmogenic cardiomyopathy [ACM], 15 dilated cardiomyopathy [DCM]) who had undergone VT ablation with >50% of the diastolic pathway of the VT circuit recorded were studied. AVS were classified into late potentials (LPs) and continuous fractionated ventricular signals (CFVS), and their characteristics and correlation with the diastolic pathway of VT circuits were analyzed.Results: Seventy-five VT circuits were analyzed. Bipolar scars were greatest in ICM endocardially (53 cm2 ICM vs 36 cm2 ACM vs 25 cm2 DCM; P = .010) and in ACM epicardially (98 cm2 ACM vs 25 cm2 ICM vs 24 cm2 DCM; P = .005). Location of the VT diastolic interval coincided with AVS location in 54% of VTs in ICM, 89% in ACM, and 72% in DCM (P = .036). There was a trend toward a greater association of diastolic intervals coinciding with LPs than with CFVS (78% vs 57%; P = .052) (69% diastolic intervals in ICM coincided with LPs, 33% with CFVS; P = .063). All patients (100%) with CFVS in ACM had VT diastolic components arising from CFVS (33% ICM, 64% DCM; P = .049). Positive predictive value for LPs vs CFVS was 77.8% vs 56.7%, and sensitivity was 67.3% vs 32.7%, respectively.Conclusion: The nature of abnormal signals in different cardiomyopathies reflects underlying pathology. LPs rather than CFVS seem to be more linked to diastolic components of VT circuits, especially in ICM. LPs have greater sensitivity and specificity for VT; however, CFVS may be of more relevance in ACM. [ABSTRACT FROM AUTHOR]

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan has no recognized role in diagnosis, prognosis, and disease monitoring in patients with arrhythmic myocarditis. The purpose of this study was to investigate the value of FDG-PET scan in arrhythmic myocarditis. The authors enrolled 75 consecutive patients (age 47 ± 14 years, 65% men) undergoing FDG-PET scan for arrhythmic myocarditis. Myocarditis was diagnosed by endomyocardial biopsy (EMB) and, whenever applicable, cardiac magnetic resonance (CMR). Indications for FDG-PET scan included either contraindication to CMR (n = 50) or mismatch between CMR and EMB (n = 25). Overall, 50 patients (67%) had positive FDG-PET. Sensitivity was 75% referring to EMB, and 73% to CMR. Specificity was 67% referring to EMB, and 59% to CMR. FDG-PET accuracy was lower in the presence of borderline myocarditis, and either late (>30 days) or on-immunosuppression FDG-PET scanning. Anteroseptal distribution pattern, found in 12 of 50 (24%) patients including 7 of 7 cardiac sarcoidosis cases, was associated with greater occurrence of ventricular arrhythmias and atrioventricular blocks in 4.2 ± 1.7 years of follow-up (10 of 12 vs 7 of 38, and 7 of 12 vs 0 of 38, respectively; both P < 0.001). In 39 patients (52%), FDG-PET was repeated by 13 ± 2 months, allowing immunosuppression withdrawal after FDG uptake normalization either by first (76%) or second reassessment (24%). FDG-PET scan may be a clinically useful diagnostic technique in arrhythmic myocarditis, in particular when CMR is unsuitable because of irregular heartbeat or implantable cardioverter-defibrillator–related artifacts. Anteroseptal FDG distribution is associated with a worse arrhythmic outcome and should raise the suspicion of cardiac sarcoidosis. During follow-up, repeated FDG-PET allows myocarditis monitoring to guide immunosuppression withdrawal. [Display omitted] [ABSTRACT FROM AUTHOR]

The authors investigated the preprocedural predictors of postprocedural intra-aortic balloon pump (IABP) need in patients undergoing transcatheter ventricular tachycardia (VT) ablation on venoarterial (VA) extracorporeal membrane oxygenation (ECMO). Observational study. Hybrid operating room and intensive care unit of a teaching hospital. Participants were 121 consecutive patients with unstable VT undergoing transcatheter ablation with VA-ECMO. In patients with postprocedural echocardiographic, radiographic, or hemodynamic signs of increased left ventricle afterload, an IABP was positioned. Patients in the IABP group were more frequently on angiotensin-converting enzyme inhibitors (58% v 37%; p = 0.03) and had lower median baseline ejection fraction (25% v 28% p = 0.05), larger end-diastolic diameter (69.7 mm ± 13.0 v 65.7 mm ± 11.3; p = 0.03), and more frequent ischemic etiology as the reason for dilated cardiomyopathy (76% v 47%; p = 0.04,) when compared with patients not requiring IABP. Postoperatively, the IABP group required longer mechanical ventilation (24 hours [20-56.5] v 23 hours [15-28]; p = 0.003), intensive care unit stay (78 hours [46-174] v 48 hours [24-72]; p < 0.001), and continuous renal replacement therapy (13.3% v 1.3%; p = 0.006). By multivariate analysis, end-diastolic diameter (odds ratio [OR]:1.08; confidence interval [CI]: 1.00-1.16; p = 0.049), ischemic dilated cardiomyopathy (OR: 8.40; CI: 2.15-32.88; p = 0.002), and more-than-moderate mitral regurgitation (OR: 4.83; CI: 1.22-19.22; p = 0.025) were independent predictors of need for IABP. The need for an IABP to unload the left ventricle can be predicted by ventricular size, medium-severe mitral valvular defect, and ischemic etiology of the dilated cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: Interest has grown in recent years in bipolar radiofrequency ablation (B-RFA). However, indications and outcome in patients with ventricular tachycardia (VT) are still to be defined.Objective: The purpose of this study was to describe patient selection, safety and effectiveness of B-RFA, in a pilot cohort study of patients with nonischemic dilated cardiomyopathy (NIDCM) and drug-refractory VT.Methods: We enrolled 21 patients with NIDCM (mean age 66±10 years; 18/21 (86%) men; left ventricular ejection fraction 35%±14%; 100% redo procedures) scheduled for a B-RFA procedure because of drug-refractory VT of suspected septal (interventricular septum [IVS]) origin. After electroanatomic mapping by using the CARTO®3 system, B-RFA was performed in all patients. Short- and long-term outcomes, including procedural success, major complications, and occurrence of major ventricular arrhythmias (MVAs), were evaluated at 25±8 months of follow-up (FU).Results: Endocardial mapping showed IVS scar in all patients and extra-IVS in 7 patients (33%). B-RFA was performed at an average power of 33 W, for 60-90 seconds, over a 4.1 cm2 area, with 13±3 mm distance between catheters tips. The impedance drop was 27±4 Ω. The primary end point of noninducibility of the target clinical VT was obtained in 20 patients (95%). During FU, MVAs were documented in 7 patients (33%). FU MVAs occurred in all (100%) patients with extra-IVS localizations (7 of 7) or inflammatory nonischemic cardiomyopathy etiology (2 of 2). IVS thinning (tip-to-tip catheter distance < 5 mm) represented the only anatomical limitation to B-RFA.Conclusion: B-RFA is feasible in patients with NIDCM and drug-refractory VT of septal origin. Extra-IVS substrate and inflammatory NIDCM etiology were associated with an adverse outcome. [ABSTRACT FROM AUTHOR]

Background: The isthmus of ventricular tachycardia (VT) circuits has been extensively characterized. Few data exist regarding the contribution of the outer loop (OL) to the VT circuit.Objective: The purpose of this study was to characterize the electrophysiological properties of the OL.Methods: Complete substrate activation mapping during sinus rhythm (SR) and full activation mapping of the VT circuit with high-density mapping were performed. Maps were analyzed mathematically to reconstruct conduction velocities (CVs) within the circuit. CV >100 cm/s was defined as normal and <50 cm/s as slow. Electrograms along the entire circuit were analyzed for fractionation, duration, and amplitude.Results: Six postmyocardial infarction patients were enrolled. The VT circuit was a figure-of-eight reentrant circuit in 4 patients and a single-loop circuit in 2 patients. The OL exhibited a mean of 1.9 ± 0.9 and 1.6 ± 0.5 corridors of slow conduction (SC) during VT and SR, respectively. SC in the OL were longer and faster than SC in the isthmus during SR. At the OL, SC sites showed local abnormal ventricular activity in 92%, and a bipolar voltage <0.5 mV was identified in 80.7%. Of the double-loop circuits, only 1 patient had fixed lines of block as isthmus boundaries, whereas in 3 patients the circuits were at least partially functional.Conclusion: In ischemic reentrant VT circuits, the OL contributes significantly to reentry with multiple corridors of SC. These corridors can result from structural or functional phenomena. Isthmus boundaries may correspond to functional or fixed lines of block. [ABSTRACT FROM AUTHOR]

Background: Triadin is a protein expressed in cardiac and skeletal muscle that has an essential role in the structure and functional regulation of calcium release units and excitation-contraction coupling. Mutations in the triadin gene (TRDN) have been described in different forms of human arrhythmia syndromes with early onset and severe arrhythmogenic phenotype, including triadin knockout syndrome.Objective: The purpose of this study was to characterize the pathogenetic mechanism underlying a case of severe pediatric malignant arrhythmia associated with a defect in the TRDN gene.Methods: We used a trio whole exome sequencing approach to identify the genetic defect in a 2-year-old boy who had been resuscitated from sudden cardiac arrest and had frequent episodes of ventricular fibrillation and a family history positive for sudden death. We then performed in vitro functional analysis to investigate possible pathogenic mechanisms underlying this severe phenotype.Results: We identified a novel homozygous missense variant (p.L56P) in the TRDN gene in the proband that was inherited from the heterozygous unaffected parents. Expression of a green fluorescent protein (GFP)-tagged mutant human cardiac triadin isoform (TRISK32-L56P-GFP) in heterologous systems revealed that the mutation alters protein dynamics. Furthermore, when co-expressed with the type 2 ryanodine receptor, caffeine-induced calcium release from TRISK32-L56P-GFP was relatively lower compared to that observed with the wild-type construct.Conclusion: The results of this study allowed us to hypothesize a pathogenic mechanism underlying this rare arrhythmogenic recessive form, suggesting that the mutant protein potentially can trigger arrhythmias by altering calcium homeostasis. [ABSTRACT FROM AUTHOR]

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the 2009 EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. An expert writing group, after reviewing and discussing the literature, including a systematic review and meta-analysis published in conjunction with this document, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Each recommendation is presented in knowledge byte format and is accompanied by supportive text and references. Further sections provide a practical synopsis of the various techniques and of the specific ventricular arrhythmia sites and substrates encountered in the electrophysiology lab. The purpose of this document is to help electrophysiologists around the world to appropriately select patients for catheter ablation, to perform procedures in a safe and efficacious manner, and to provide follow-up and adjunctive care in order to obtain the best possible outcomes for patients with ventricular arrhythmias. [ABSTRACT FROM AUTHOR]

The study sought to assess the long-term outcomes of the stand-alone Cox-Maze IV procedure in symptomatic patients with refractory, persistent, or long-standing persistent atrial fibrillation (AF). Fifty-nine consecutive patients (mean age 52 ± 10.5 years, previous catheter ablation 80%, left ventricular ejection fraction 55% ± 3.4%, median left atrial volume index 41 [interquartile range, 34-47] mL/m2) with symptomatic, refractory, persistent (56%), or longstanding persistent (44%) AF, underwent stand-alone Cox-Maze IV procedure. Biatrial ablations were performed with bipolar radiofrequency and cryoenergy. Left atrial appendage was excluded in 56 of 59 (95%) patients. No hospital deaths occurred and 1 (1.7%) patient required postoperative pacemaker implantation. Follow-up was 97% complete (median 5.8 [interquartile range, 3.92-7.11] years). The overall survival at 7 years was 97% ± 2.3%. The 7-year cumulative incidence function of AF recurrence and of AF recurrence off class I or III antiarrhythmic drugs (AADs), with death as competing risk, was 14.2% ± 5.6% (95% confidence interval [CI], 5.5%-26.8%) and 26.5% ± 6.9% (95% CI, 14.2%-40.4%), respectively. Multivariate analysis identified the duration of AF as the only predictor of AF recurrence (hazard ratio, 1.01; 95% CI, 1.01-1.02; P <.001). At 7 years, the proportion of patients in sinus rhythm was 84%, of whom 74% were off class I or III AADs. At the last follow-up, 75% of patients were in European Heart Rhythm Association functional class I, no stroke and thromboembolic events were documented, and 70% of patients were off anticoagulation therapy. Left ventricular ejection fraction improved from 53% ± 3.4% at baseline to 59% ± 3.4% at follow-up (P =.003). This study confirmed the safety and efficacy in the long term (7 years) of the stand-alone Cox-Maze IV surgical procedure for persistent or long-standing persistent AF. Indeed, more than 70% of the patients were in sinus rhythm off class I or III AADs and off oral anticoagulation. [ABSTRACT FROM AUTHOR]

Many kinds of arrhythmias may occur in patients with myocarditis at any stage of the disease. However, compared to the other clinical presentations, arrhythmic myocarditis has been poorly described in the literature. Arrhythmias occurring in either ongoing or previous myocardial inflammation are complex and heterogeneous, and the disease itself is often underdiagnosed, thus limiting data collection and interpretation. However, different from the other clinical presentations, arrhythmic myocarditis requires specific diagnostic, prognostic, and therapeutic considerations. The aim of this review is to critically summarize the state of the art on myocarditis presenting with arrhythmias in terms of epidemiology, etiology, diagnosis, prognosis, and treatment. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Infections represent one of the most frequent causes of arthroplasty revision. Thus, design of new antimicrobial scaffolds to reduce implant rejections, bone infections and associated medical costs is highly desired. In recent years, essential oil components (EOCs) have merged as compounds with significant antimicrobial activity that can be attached to specific surfaces to enhance and prolong their antimicrobial effect. Herein calcium phosphate CaP regenerative materials have been coated with a vanillin derivative to combine its original bone regeneration properties with antimicrobial action of EOCs. Materials in form of microparticles and blocks were prepared and fully characterized. Clonogenic viability tests demonstrated that low concentrations of material (10 mg·mL−1) resulted effective to kill 100% of E. coli DH5α bacteria. Additionally, vanillin containing scaffolds did not display any toxic effect over cells, yet they preserve the ability to express alkaline phosphatase (ALPL) , collagen type 1, chain α1 (COL1A1) and bone gamma-carboxyglutamic acid-containing protein or osteocalcin (BGLAP), which are genes typically expressed by osteoblasts. These results demonstrate that commercially available scaffolds can be functionalized with EOCs, achieving antimicrobial activity and open up a new approach for the treatment and prevention of infection. Statement of significance During the last years, the interest in bone regenerative materials with antibiotic properties has increased, since prosthesis infection is one of the most usual complications in implant surgery. In this work, we report a hybrid system composed by a calcium phosphate material (powders and scaffolds) functionalized with the derivative of an essential oil component (EOC). Our purpose was to provide the calcium phosphate material with antimicrobial activity without harming its bone regenerative capability. The obtained results were encouraging, which opens up the possibility of developing new modified materials for the prevention and treatment of bone infection. [ABSTRACT FROM AUTHOR]

Catheter ablation of ventricular tachycardia (VT) has evolved in recent years, especially in patients with ischemic heart disease. Data from prospective studies show that VT catheter ablation reduces the risk of recurrent VT; however, there is a paucity of data on the effect of VT catheter ablation on mortality and patient-centered outcomes such as quality of life. Performing randomized clinical trials of VT catheter ablation can be fraught with challenges, and, as a result, several prior trials of VT catheter ablation had to be stopped prematurely. The main challenges are inability to blind the patient to therapy to obtain a traditional control group, high crossover rates between the 2 arms of the study, patient refusal to participate in trials in which they have an equal chance of receiving a "pill" vs an invasive procedure, heterogeneity of mapping and ablation techniques as well as catheters and equipment, rapid evolution of technology that may make findings of any long trial less relevant to clinical practice, lack of consensus on what constitutes acute procedural and long-term success, and presentation of patients to electrophysiologists late in the course of their disease. In this article, a panel of experts on VT catheter ablation and/or clinical trials of VT catheter ablation review challenges faced in conducting prior trials of VT catheter ablation and offer potential solutions for those challenges. It is hoped that the proposed solutions will enhance the feasibility of randomized clinical trials of VT catheter ablation. [ABSTRACT FROM AUTHOR]

Objectives This study sought to compare myocardial scars depicted by computed tomography (CT) with electrical features from electro-anatomic mapping (EAM), assessing the potential role of CT integration in ventricular tachycardia (VT) and radiofrequency catheter ablation (RFCA) procedures. Background Imaging-based characterization of VT myocardial substrate is required to plan EAM and, potentially, to guide RFCA. Methods Forty-two consecutive patients, 35 of whom had implantable cardioverter-defibrillator, all referred for VT RFCA, underwent pre-procedural CT including an angiographic and a 10-min delayed-enhancement scan. Segmental comparison between scars segmented from CT and low voltages (bipolar voltages <1.5 mV; unipolar voltages <8 mV), late potentials, and RF ablation points on EAM, was carried out. In a subset of 16 consecutive patients, a further point-by-point analysis was performed: a CT-derived 3-dimensional structure including heart anatomy and myocardial scars was integrated with EAM for quantitative comparison. Results CT scans identified scars in 39 patients and defined left ventricular wall involvement and mural distribution. Overall segmental concordance between CT and EAM was good (κ = 0.536) despite the presence of implantable cardioverter-defibrillator, scar etiologies, and mural distribution. CT identified segments characterized by low voltages with good sensitivity (76%), good specificity (86%), and very high negative predictive value (95%). Late potentials and RF ablation points fell on scarred segments identified from CT in 79% and 81% of cases, respectively. Point-by-point quantitative comparison revealed good correlation between the average area of scar detected at CT and at bipolar mapping (CT = 4,901 mm 2 , bipolar voltages-EAM = 4,070 mm 2 ; R = 0.78; p < 0.0001). In this study, 70% and 84% of low-amplitude bipolar points were mapped at a maximum distance of 5 mm and 10 mm from CT-segmented scar, respectively. Conclusions CT with delayed-enhancement provides a 3-dimensional characterization of VT scar substrate together with a detailed anatomic model of the heart. This information may offer assistance to plan EAM and RFCA procedures and is potentially suitable for EAM-imaging integration. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Circulating endothelial progenitor cells (EPCs) may play a crucial role during pregnancy by sustaining adequate placentation and fetal growth. Unambiguous demonstration of EPC increase during pregnancy has been hampered so far by lack of standardized methods for EPC quantification. In this study we used the currently most accepted phenotype for EPC detection for investigating whether maternal circulating EPCs might increase during normal pregnancy and whether they may fail to increase in pregnancy complicated by idiopathic intrauterine growth restriction (IUGR), a leading cause of perinatal mortality and morbidity characterized by insufficient placental perfusion. Methods: Twenty-one non-pregnant women, 44 women during healthy pregnancy progression (9, 13 and 22 women in the first, second and third trimester, respectively) and 11 with pregnancy complicated by idiopathic IUGR were recruited in a cross-sectional study. EPCs in maternal blood were identified as CD45dim/CD34+/KDR+ cells by flow cytometry. Plasmatic cytokines were measured by ELISA. Results: We observed a significant and progressive increase of EPCs in normal pregnancy, yet detectable in early pregnancy but even more pronounced in the third trimester. The increase of EPCs was impaired in IUGR-complicated pregnancies at comparable gestational age. The circulating levels of placental growth-factor and stromal-derived-factor-1 were significantly lower in IUGR than normal pregnancies, possibly contributing to EPC impairment. Conclusions: EPC count in maternal circulation may have a great potential as a novel biomarker for pregnancy monitoring and may represent the target of novel therapeutic strategies designed to prevent adverse pregnancy outcomes often occurring in IUGR. [Copyright &y& Elsevier]

Abstract: Introduction: The state of activation of dendritic cells (DCs) at the feto-maternal interface critically contributes to optimal decidual immune responses needed to support fetal-placental development. We recently demonstrated that during healthy pregnancy also peripheral blood DCs (PBDCs), which are easily accessible, are activated as well. In this study, to investigate a possible involvement of DCs in intrauterine growth restriction (IUGR), we evaluated whether PBDCs in pregnancy complicated by IUGR may be altered compared with PBDCs in healthy pregnancy. Methods: PBDCs from 12 pregnant women with primary IUGR, 21 healthy pregnant and 19 nonpregnant women were analyzed by flow cytometric analysis of whole-blood samples collected at a single time point. Results: The number of plasmacytoid PBDCs was significantly reduced in women with IUGR pregnancy. Myeloid and plasmacytoid PBDCs in IUGR lacked the state of activation (assessed as CD80, CD86, CD40 expression) and the shift to a proinflammatory pattern of cytokine production occurring during healthy pregnancy. Discussion: To our knowledge, this is the first study investigating the state of PBDC activation in IUGR pregnancy. Our results are in accordance with a previous study reporting a lower expression of activation and maturation markers by decidual DCs in IUGR placentas. Conclusions: The reduced activation of PBDCs in IUGR pregnancy may possibly reflect a reduced activation of decidual DCs. If confirmed at the feto-maternal interface, the alterations of DCs described in IUGR pregnancy have the potential to negatively impact on vascular development during gestation. These observations may therefore broaden our understanding of IUGR pathogenesis. [Copyright &y& Elsevier]

Background: CHA2DS2-VASc is a validated score for predicting stroke in patients with atrial fibrillation (AF).Objective: The purpose of this study was to assess whether the CHA2DS2-VASc score can predict new-onset AF in a cohort of patients with a cardiac implantable electronic device (CIED) followed with remote monitoring.Methods: Using the database of the Home Monitoring Expert Alliance project, we selected 2410 patients with no documented AF who had received a CIED with diagnostics on atrial high rate episodes (AHREs). The primary endpoint was time to first day with cumulative AHRE burden ≥15 minutes, 5 hours, 24 hours, and ≥7 consecutive days.Results: During a median duration of 24.1(11.5-42.9) months, the incidence of AHRE increased with increasing CHA2DS2-VASc. At 6 years, occurrence of ≥15-minute AHRE was 80.2% (CHA2DS2-VASc ≤1) vs 93.7% (CHA2DS2-VASc ≥5), whereas ≥5-hour AHRE incidence was 68.4% (CHA2DS2-VASc ≤1) vs 92.5% (CHA2DS2-VASc ≥5). Occurrence of ≥24-hour and ≥7-day AHREs also increased with increasing CHA2DS2-VASc: 9.1% and 3.9% (CHA2DS2-VASc ≤1) vs 40.4% and 28.7% (CHA2DS2-VASc ≥5), respectively. Adjusted hazard ratio for unitary CHA2DS2-VASc increase ranged from 1.09 (confidence interval 1.04-1.14; P <.001) with AHRE burden ≥15 minutes to 1.26 (confidence interval 1.11-1.42; P <.001) with AHRE burden ≥7 days. At receiver operating curve analysis, CHA2DS2-VASc ≥2 was estimated to predict persistent forms of AHREs with 95.8% sensitivity but 11.7% specificity at 3 years. CHA2DS2-VASc ≥5 had 77.0% specificity but 34.6% sensitivity.Conclusion: In a CIED population with no previous diagnosis of clinical AF, AHRE incidence increased with increasing CHA2DS2-VASc score. The association was stronger with longer AHREs, but the accuracy of CHA2DS2-VASc as AHRE predictor was moderate. [ABSTRACT FROM AUTHOR]

Background & Aims Alterations in signaling pathways that regulate resolution of inflammation (resolving pathways) contribute to pathogenesis of ulcerative colitis (UC). The resolution process is regulated by lipid mediators, such as those derived from the ω-3 docosahexaenoic acid (DHA), whose esterified form is transported by the major facilitator superfamily domain containing 2A (MFSD2A) through the endothelium of brain, retina, and placenta. We investigated if and how MFSD2A regulates lipid metabolism of gut endothelial cells to promote resolution of intestinal inflammation. Methods We performed lipidomic and functional analyses of MFSD2A in mucosal biopsies and primary human intestinal microvascular endothelial cells (HIMECs) isolated from surgical specimens from patients with active, resolving UC and healthy individuals without UC (controls). MFSD2A was knocked down in HIMECs with small hairpin RNAs or overexpressed from a lentiviral vector. Human circulating endothelial progenitor cells that overexpress MFSD2A were transferred to CD1 nude mice with dextran sodium sulfate–induced colitis, with or without oral administration of DHA. Results Colonic biopsies from patients with UC had reduced levels of inflammation-resolving DHA-derived epoxy metabolites compared to healthy colon tissues or tissues with resolution of inflammation. Production of these metabolites by HIMECs required MFSD2A, which is required for DHA retention and metabolism in the gut vasculature. In mice with colitis, transplanted endothelial progenitor cells that overexpressed MFSD2A not only localized to the inflamed mucosa but also restored the ability of the endothelium to resolve intestinal inflammation, compared with mice with colitis that did not receive MFSD2A-overexpressing endothelial progenitors. Conclusions Levels of DHA-derived epoxides are lower in colon tissues from patients with UC than healthy and resolving mucosa. Production of these metabolites by gut endothelium requires MFSD2A; endothelial progenitor cells that overexpress MFSD2A reduce colitis in mice. This pathway might be induced to resolve intestinal inflammation in patients with colitis. [ABSTRACT FROM AUTHOR]

Introduction: Monomorphic sustained ventricular tachycardia (MSVT) in structural heart disease (SHD) carries poor prognosis and usually needs ICD implantation. Whether successful RF ablation of VT in this setting could avoid the need of ICD implantation is largely unknown. Methods: 105 successive with SHD (88 men, age 64±16) were followed after RF ablation of MSVT. An ICD was not implanted either because of end stage extra cardiac pathology, advanced age or well-tolerated MSVT and preserved EF. 33% were on amiodarone and 51% on beta-blockers. Results: 128 procedures were performed (1,2/pt) in 4 centers. Coronary artery disease was present in 54%, right ventricular dysplasia in 10%, dilated cardiomyopathy in 10% and various SHD in 26%. Mean EF was 48±12% (14% with EF<0,35). VT was well tolerated in 77% (169±32bpm) with syncope or near-syncope in 23%. 11% presented with electrical storm. Ablation was performed using various techniques and end points. Complete acute success was considered achieved in 80% and undetermined in 5 pts. Not any VT was induced in 92% at the end of the procedure. Complications were arterial dissection/occlusion (2 pts), tamponnade (1 pt), AV block (1 pt) and hematomas (4 pts). Patients were discharged on beta-blockers (63%) and amiodarone (29%). Mean follow-up was 21±16 months. VT recurred in 14% (7±5 months) without compromise of the vital status. Mortality rate was 11% (no SD) (16±15 months). Additional RF ablations were performed again in 14 pts with recurring VT and VT further recurred in 4 while SD occurred in 2. Final VT recurrence rate including redo precedures was 14%. An ICD was finally implanted in 5 pts. There was no difference in VT recurrence rate according to the cardiopathy, clinical variables, EF, VT rate and tolerance or to residual VT inducibility. Conclusions: RF ablation for VT occurring in pts with SHD without ICD appears safe and efficient and might be now proposed as an alternative for ICD implantation because of associated morbidity, advanced age or when VT is well tolerated and does not occur in the context of advanced heart disease. [Copyright &y& Elsevier]

Objectives: This study sought to compare clinical, echocardiographic, and cardiopulmonary exercise testing response to cardiac resynchronization therapy (CRT) in patients with unfavorable anatomy of coronary sinus (CS) veins, randomized to transvenous versus surgical left ventricular (LV) lead implantation. Background: CRT efficacy depends on proper positioning of the LV lead over the posterolateral wall. A detailed pre-operative knowledge of CS anatomy might be of pivotal importance to accomplish a proper LV lead placement over this area. Methods: Study population included 40 patients (age 66 ± 4 years) with heart failure and indication to CRT, with unsuitable CS branches anatomy documented by pre-operative multislice computed cardiac tomography; 20 patients (Group 1) underwent surgical minithoracotomic LV lead implantation whereas 20 (Group 2) were implanted transvenously. New York Heart Association functional class, echocardiographic, and cardiopulmonary exercise testing data were assessed before and 1 year after CRT-system implant. Results: In all Group 1 patients, the LV leads were placed over the middle-basal segments of the posterolateral wall of the LV. This was not possible in Group 2 patients. One year after CRT, in Group 1, a significant improvement of New York Heart Association functional class, LV ejection fraction (from 28.8 ± 9.2% to 33.9 ± 7.2%, p < 0.01), LV end-systolic volume (from 165 ± 53 ml to 134 ± 48 ml, p < 0.001), and peak Vo(2)/kg (from 10.4 ± 4.5 ml/kg/min to 13.1 ± 3.1 ml/kg/min, p < 0.02) was observed. However, no improvement was observed in Group 2: LV ejection fraction varied from 27.4 ± 4.8% to 27.4 ± 5.7% (p = 0.9), LV end-systolic volume from 175 ± 46 ml to 166 ± 44 ml (p = 0.15), and peak Vo(2)/kg from 11.2 ± 3.2 ml/kg/min to 11.3 ± 3.4 ml/kg/min (p = 0.9). Changes after CRT between groups were highly significant. Conclusions: In the setting of unfavorable CS branches of anatomy, CRT by a surgical minithoracotomic approach is preferable to transvenous lead implantation. [ABSTRACT FROM AUTHOR]

Modulation of atrioventricular (AV) node conduction and radiofrequency ablation of AV junction are alternative approaches to control ventricular rate in drug refractory atrial fibrillation (AF). In 2 centers, 120 patients were treated either with AV junction ablation (center 1, group 1, 60 patients [30 men, aged 64 +/- 11 years], paroxysmal AF in 24 patients) or with modulation (group 2, 60 patients [32 men, aged 58 +/- 12 years], paroxysmal AF in 43 patients). In group 1, complete AV block was achieved in all patients. In group 2, the procedure was performed in sinus rhythm (30 patients), prolonging the Wenckebach cycle length from 328 +/- 85 to 466 +/- 80 ms (p <0.01) or during AF (30 patients), decreasing ventricular rate from 178 +/- 35 to 96 +/- 35 beats/min (p <0.01), and to <100 beats/min in 17 patients (61%). Complete AV block was induced in 9 of 60 patients (15%). In groups 1 and 2, at a follow-up of 27 +/- 7 and 26 +/- 6 months, there were 2 deaths (1 cardiac, 1 sudden death) and 1 death for end-stage heart failure, respectively. Hospital readmissions decreased from 3.2 to 0.2 and from 4.2 to 0.2/year; late AF recurrences at of >120 beats/min were documented in 6% and 12%, respectively. Symptom score analysis including effort and rest dyspnea, exercise intolerance, weakness, and palpitation showed a significant improvement in both treatment groups, when acutely effective, in patients with paroxysmal and/or chronic AF. In conclusion, ablation of the AV junction shows a higher acute success rate compared with modulation of the AV node conduction in patients with drug refractory AF. Depending on the acute success, both approaches therefore were similarly effective in achieving long-term ventricular rate control and symptom score improvement. [ABSTRACT FROM AUTHOR]