Fasting and Glucose Metabolism Differentially Impact Peripheral Inflammation in Human Type 2 Diabetes.

Cytokines produced by peripheral T-helper 1/17 cells disproportionately contribute to the inflammation (i.e., metaflammation) that fuels type 2 diabetes (T2D) pathogenesis. Shifts in the nutrient milieu could influence inflammation through changes in T-cell metabolism. We aimed to determine whether changes in glucose utilization alter cytokine profiles in T2D. Peripheral blood mononuclear cells (PBMCs), CD4+ T-cells, and CD4+CD25- T-effector (Teff) cells were isolated from age-matched humans classified by glycemic control and BMI. Cytokines secreted by CD3/CD28-stimulated PBMCs and Teff were measured in supernatants with multiplex cytokine assays and a FLEXMAP-3D. Metabolic activity of stimulated CD4+ T-cells was measured by a Seahorse XFe96 analyzer. In this study, we demonstrated that T-cell stimulated PBMCs from non-fasted people with T2D produced higher amounts of cytokines compared to fasting. Although dysglycemia characterizes T2D, cytokine production by PBMCs or CD4+ T-cells in T2D was unaltered by hyperglycemic media. Moreover, pharmacological suppression of mitochondrial glucose oxidation did not change T-cell metabolism in T2D, yet enhanced cytokine competency. In conclusion, fasting and glucose metabolism differentially impact peripheral inflammation in human T2D, suggesting that glucose, along with fatty acid metabolites per our previous work, partner to regulate metaflammation. These data expose a major disconnect in the use of glycemic control drugs to target T2D-associated metaflammation.

Everolimus alleviates CD4+ T cell inflammation by regulating autophagy and cellular redox homeostasis.

Aging is associated with the onset and progression of multiple diseases, which limit health span. Chronic low-grade inflammation in the absence of overt infection is considered the simmering source that triggers age-associated diseases. Failure of many cellular processes during aging is mechanistically linked to inflammation; however, the overall decline in the cellular homeostasis mechanism of autophagy has emerged as one of the top and significant inducers of inflammation during aging, frequently known as inflammaging. Thus, physiological or pharmacological interventions aimed at improving autophagy are considered geroprotective. Rapamycin analogs (rapalogs) are known for their ability to inhibit mTOR and thus regulate autophagy. This study assessed the efficacy of everolimus, a rapalog, in regulating inflammatory cytokine production in T cells from older adults. CD4+ T cells from older adults were treated with a physiological dose of everolimus (0.01 µM), and indices of autophagy and inflammation were assessed to gain a mechanistic understanding of the effect of everolimus on inflammation. Everolimus (Ever) upregulated autophagy and broadly alleviated inflammatory cytokines produced by multiple T cell subsets. Everolimus's ability to alleviate the cytokines produced by Th17 subsets of T cells, such as IL-17A and IL-17F, was dependent on autophagy and antioxidant signaling pathways. Repurposing the antineoplastic drug everolimus for curbing inflammaging is promising, given the drug's ability to restore multiple cellular homeostasis mechanisms.

Personalized voltage maps guided by cardiac magnetic resonance in the era of high-density mapping.

BACKGROUND: Voltage mapping could identify the conducting channels potentially responsible for ventricular tachycardia (VT). Standard thresholds (0.5-1.5 mV) were established using bipolar catheters. No thresholds have been analyzed with high-density mapping catheters. In addition, channels identified by cardiac magnetic resonance (CMR) has been proven to be related with VT. OBJECTIVE: The purpose of this study was to analyze the diagnostic yield of a personalized voltage map using CMR to guide the adjustment of voltage thresholds. METHODS: All consecutive patients with scar-related VT undergoing ablation after CMR (from October 2018 to December 2020) were included. First, personalized CMR-guided voltage thresholds were defined systematically according to the distribution of the scar and channels. Second, to validate these new thresholds, a comparison with standard thresholds (0.5-1.5 mV) was performed. Tissue characteristics of areas identified as deceleration zones (DZs) were recorded for each pair of thresholds. In addition, the relation of VT circuits with voltage channels was analyzed for both maps. RESULTS: Thirty-two patients were included [mean age 66.6 ± 11.2 years; 25 (78.1%) ischemic cardiomyopathy]. Overall, 52 DZs were observed: 44.2% were identified as border zone tissue with standard cutoffs vs 75.0% using personalized voltage thresholds (P = .003). Of the 31 VT isthmuses detected, only 35.5% correlated with a voltage channel with standard thresholds vs 74.2% using adjusted thresholds (P = .005). Adjusted cutoff bipolar voltages that better matched CMR images were 0.51 ± 0.32 and 1.79 ± 0.71 mV with high interindividual variability (from 0.14-1.68 to 0.7-3.21 mV). CONCLUSION: Personalized voltage CMR-guided personalized voltage maps enable a better identification of the substrate with a higher correlation with both DZs and VT isthmuses than do conventional voltage maps using fixed thresholds.

Same-day discharge after atrial fibrillation ablation under a nurse-coordinated standardized protocol.

AIMS: Same-day discharge (SDD) after atrial fibrillation (AF) ablation is an effective means to spare healthcare resources. However, safety remains a concern, and besides structural adaptations, SDD requires more efficient logistics and coordination. Therefore, in this study, we implement a streamlined, nurse-coordinated SDD programme following a standardized protocol. METHODS AND RESULTS: As a dedicated SDD coordinator, a nurse specialized in ambulatory cardiac interventions was in charge of the full SDD protocol, including eligibility, patient flow, in-hospital logistics, patient education, and discharge as well as early post-discharge follow-up by smartphone-based virtual visits. Patients planned for AF ablation were considered eligible if they had a left ventricular ejection fraction (LVEF) ≥35%, with basic support at home and accessibility of the hospital within 60 min also forming a part of the eligibility criteria. A total of 420 consecutive patients were screened by the SDD coordinator, of whom 331 were eligible for SDD. The reasons for exclusion were living remotely (29, 6.9%), lack of support at home (19, 4.5%), or LVEF <35% (17, 4.0%). Of the eligible patients, 300 (91%) were successfully discharged the same day. There were no major post-SDD complications. Rates of unplanned medical attention (19, 6.3%) and 30-day readmission (5, 1.6%) were extremely low and driven by femoral access-site complications. These were significantly reduced upon the introduction of compulsory ultrasound-guided punctures after the initial 150 SDD patients (P = 0.0145). Standardized SDD coordination resulted in efficient workflows and reduced the total workload of the medical staff. CONCLUSION: Same-day discharge after AF ablation following a nurse-coordinated standardized protocol is safe and efficient. The concept of ambulatory cardiac intervention nurses functioning as dedicated coordinators may be key in the future transition of hospitals to SDD. Ultrasound-guided femoral puncture virtually eliminated relevant femoral access-site complications in our cohort and should therefore be a prerequisite for SDD.

Catheter Ablation of Ventricular Tachycardia in Ischemic Heart Disease: What Is Known and New Perspectives.

PURPOSE OF THE REVIEW: This review aims to evaluate current evidence regarding ventricular tachycardia ablation in patients with ischemic heart disease and explore novel approaches currently developing to improve procedural and long-term outcomes. RECENT FINDINGS: Recently published trials (PARTITA, PAUSE-SCD, and SURVIVE-VT) have demonstrated the prognostic benefit of prophylactic ventricular tachycardia ablation compared to current clinical practice. Advanced cardiac imaging provides a valuable pre-procedural evaluation of the arrhythmogenic substrate, identifying ablation targets non-invasively. Advanced cardiac mapping techniques allow to better characterize arrhythmogenic substrate during ablation procedure. Emerging technologies like pulsed field ablation and ultra-low temperature cryoablation show promise in ventricular tachycardia ablation. Advancements in mapping techniques, ablation technologies, and pre-procedural cardiac imaging offer promise for improving ventricular tachycardia ablation outcomes in ischemic heart disease.

Validation of ActiGraph and Fitbit in the assessment of energy expenditure in Huntington's disease.

BACKGROUND: Consumer and research activity monitors have become popular because of their ability to quantify energy expenditure (EE) in free-living conditions. However, the accuracy of activity trackers in determining EE in people with Huntington's Disease (HD) is unknown. RESEARCH QUESTION: Can the ActiGraph wGT3X-B or the Fitbit Charge 4 accurately measure energy expenditure during physical activity, in people with HD compared to Indirect Calorimetry (IC) (Medisoft Ergo Card)? METHODS: We conducted a cross-sectional, observational study with fourteen participants with mild-moderate HD (mean age 55.7 ± 11.4 years). All participants wore an ActiGraph and Fitbit during an incremental test, running on a treadmill at 3.2 km/h and 5.2 km/h for three minutes at each speed. We analysed and compared the accuracy of EE estimates obtained by Fitbit and ActiGraph against the EE estimates obtained by a metabolic cart, using with Intra-class correlation (ICC), Bland-Altman analysis and correlation tests. RESULTS: A significant correlation and a moderate reliability was found between ActiGraph and IC for the incremental test (r = 0.667)(ICC=0.633). There was a significant correlation between Fitbit and IC during the incremental test (r = 0.701), but the reliability was poor at all tested speeds in the treadmill walk. Fitbit significantly overestimated EE, and ActiGraph underestimated EE compared to IC, but ActiGraph estimates were more accurate than Fitbit in all tests. SIGNIFICANCE: Compared to IC, Fitbit Charge 4 and ActiGraph wGT3X-BT have reduced accuracy in estimating EE at slower walking speeds. These findings highlight the need for population-specific algorithms and validation of activity trackers.

Non-invasive detection of slow conduction with cardiac magnetic resonance imaging for ventricular tachycardia ablation.

AIMS: Non-invasive myocardial scar characterization with cardiac magnetic resonance (CMR) has been shown to accurately identify conduction channels and can be an important aid for ventricular tachycardia (VT) ablation. A new mapping method based on targeting deceleration zones (DZs) has become one of the most commonly used strategies for VT ablation procedures. The aim of the study was to analyse the capability of CMR to identify DZs and to find predictors of arrhythmogenicity in CMR channels. METHODS AND RESULTS: Forty-four consecutive patients with structural heart disease and VT undergoing ablation after CMR at a single centre (October 2018 to July 2021) were included (mean age, 64.8 ± 11.6 years; 95.5% male; 70.5% with ischaemic heart disease; a mean ejection fraction of 32.3 ± 7.8%). The characteristics of CMR channels were analysed, and correlations with DZs detected during isochronal late activation mapping in both baseline maps and remaps were determined. Overall, 109 automatically detected CMR channels were analysed (2.48 ± 1.15 per patient; length, 57.91 ± 63.07 mm; conducting channel mass, 2.06 ± 2.67 g; protectedness, 21.44 ± 25.39 mm). Overall, 76.1% of CMR channels were associated with a DZ. A univariate analysis showed that channels associated with DZs were longer [67.81 ± 68.45 vs. 26.31 ± 21.25 mm, odds ratio (OR) 1.03, P = 0.010], with a higher border zone (BZ) mass (2.41 ± 2.91 vs. 0.87 ± 0.86 g, OR 2.46, P = 0.011) and greater protectedness (24.97 ± 27.72 vs. 10.19 ± 9.52 mm, OR 1.08, P = 0.021). CONCLUSION: Non-invasive detection of targets for VT ablation is possible with CMR. Deceleration zones found during electroanatomical mapping accurately correlate with CMR channels, especially those with increased length, BZ mass, and protectedness.

Post-Ablation cardiac Magnetic resonance to assess Ventricular Tachycardia recurrence (PAM-VT study).

AIMS: Conducting channels (CCs) detected by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) are related to ventricular tachycardia (VT). The aim of this work was to study the ability of post-ablation LGE-CMR to evaluate ablation lesions. METHODS AND RESULTS: This is a prospective study of consecutive patients referred for a scar-related VT ablation. LGE-CMR was performed 6-12 months prior to ablation and 3-6 months after ablation. Scar characteristics of pre- and post-ablation LGE-CMR were compared. During the study period (March 2019-April 2021), 61 consecutive patients underwent scar-related VT ablation after LGE-CMR. Overall, 12 patients were excluded (4 had poor-quality LGE-CMR, 2 died before post-ablation LGE-CMR, and 6 underwent post-ablation LGE-CMR 12 months after ablation). Finally, 49 patients (age: 65.5 ± 9.8 years, 97.9% male, left ventricular ejection fraction: 34.8 ± 10.4%, 87.7% ischaemic cardiomyopathy) were included. Post-ablation LGE-CMR showed a decrease in the number (3.34 ± 1.03 vs. 1.6 ± 0.2; P < 0.0001) and mass (8.45 ± 1.3 vs. 3.5 ± 0.6 g; P < 0.001) of CCs. Arrhythmogenic CCs disappeared in 74.4% of patients. Dark core was detected in 75.5% of patients, and its presence was not related to CC reduction (52.2 ± 7.4% vs. 40.8 ± 10.6%, P = 0.57). VT recurrence after one year follow-up was 16.3%. The presence of two or more channels in the post-ablation LGE-CMR was a predictor of VT recurrence (31.82% vs. 0%, P = 0.0038) with a sensibility of 100% and specificity of 61% (area under the curve 0.82). In the same line, a reduction of CCs < 55% had sensibility of 100% and specificity of 61% (area under the curve 0.83) to predict VT recurrence. CONCLUSION: Post-ablation LGE-CMR is feasible, and a reduction in the number of CCs is related with lower risk of VT recurrence. The dark core was not present in all patients. A decrease in VT substrate was also observed in patients without a dark core area in the post-ablation LGE-CMR.

STAT3 modulates CD4+ T mitochondrial dynamics and function in aging.

Aging promotes numerous intracellular changes in T cells that impact their effector function. Our data show that aging promotes an increase in the localization of STAT3 to the mitochondria (mitoSTAT3), which promotes changes in mitochondrial dynamics and function and T-cell cytokine production. Mechanistically, mitoSTAT3 increased the activity of aging T-cell mitochondria by increasing complex II. Limiting mitoSTAT3 using a mitochondria-targeted STAT3 inhibitor, Mtcur-1 lowered complex II activity, prevented age-induced changes in mitochondrial dynamics and function, and reduced Th17 inflammation. Exogenous expression of a constitutively phosphorylated form of STAT3 in T cells from young adults mimicked changes in mitochondrial dynamics and function in T cells from older adults and partially recapitulated aging-related cytokine profiles. Our data show the mechanistic link among mitoSTAT3, mitochondrial dynamics, function, and T-cell cytokine production.

Factors associated with the need of parenteral nutrition in critically ill patients after the initiation of enteral nutrition therapy.

Background and aims: Despite enteral nutrition (EN) is the preferred route of nutrition in patients with critical illness, EN is not always able to provide optimal nutrient provision and parenteral nutrition (PN) is needed. This is strongly associated with gastrointestinal (GI) complications, a feature of gastrointestinal dysfunction and disease severity. The aim of the present study was to investigate factors associated with the need of PN after start of EN, together with the use and complications associated with EN. Methods: Adult patients admitted to 38 Spanish intensive care units (ICUs) between April and July 2018, who needed EN therapy were included in a prospective observational study. The characteristics of EN-treated patients and those who required PN after start EN were analyzed (i.e., clinical, laboratory and scores). Results: Of a total of 443 patients, 43 (9.7%) received PN. One-third (29.3%) of patients presented GI complications, which were more frequent among those needing PN (26% vs. 60%, p = 0.001). No differences regarding mean energy and protein delivery were found between patients treated only with EN (n = 400) and those needing supplementary or total PN (n = 43). Abnormalities in lipid profile, blood proteins, and inflammatory markers, such as C-Reactive Protein, were shown in those patients needing PN. Sequential Organ Failure Assessment (SOFA) on ICU admission (Hazard ratio [HR]:1.161, 95% confidence interval [CI]:1.053-1.281, p = 0.003) and modified Nutrition Risk in Critically Ill (mNUTRIC) score (HR:1.311, 95% CI:1.098-1.565, p = 0.003) were higher among those who needed PN. In the multivariate analysis, higher SOFA score (HR:1.221, 95% CI:1.057-1.410, p = 0.007) and higher triglyceride levels on ICU admission (HR:1.004, 95% CI:1.001-1.007, p = 0.003) were associated with an increased risk for the need of PN, whereas higher albumin levels on ICU admission (HR:0.424, 95% CI:0.210-0.687, p = 0.016) was associated with lower need of PN. Conclusion: A higher SOFA and nutrition-related laboratory parameters on ICU admission may be associated with the need of PN after starting EN therapy. This may be related with a higher occurrence of GI complications, a feature of GI dysfunction. Clinical trial registration: ClinicalTrials.gov: NCT03634943.

Identification of clinical and pharmacogenetic factors influencing metformin response in Type 2 diabetes mellitus.

Metformin, a hypoglycemic drug for Type 2 diabetes mellitus, shows variability in pharmacokinetics and response due to membrane transporters. This study followed 34 Type 2 diabetes mellitus patients on metformin treatment. Genetic variants in 11 metformin transport-related genes were analyzed, revealing associations. Specifically, SLC47A1 rs2289669 A/A and SLC22A4 rs1050152 T/T genotypes correlated with glycated hemoglobin values at 6 months. SLC47A1 rs2289669 G/A genotype influenced glucose levels at 6 months, while SLC29A4 rs3889348 A/A, SLC47A1 rs2289669 A/A, SLC22A4 rs1050152 C/T and SLC47A2 rs12943590 A/A genotypes were linked to glucose levels at 12 months. Additionally, ABCB1 rs2032582 C/A and ABCG2 rs2231137 C/T genotypes impacted cholesterol levels at 12 months. These findings shed light on metformin response determinants, offering insights for further research.

How can I assess my patients with Parkinson's disease during a busy clinic day?

BACKGROUND: The evaluation of motor impairment in Parkinson's disease (PD) is mainly assessed with the motor subdomain of the Unified Parkinson's Disease Rating scale (UPDRS part III) and, lately, with the MDS-UPDRS part III. To optimize efforts and special needs during specific circumstances in clinical practice, we sought to identify the most sensitive items to assess motor impairment in PD. METHODS: We included the COPPADIS-PD cohort and collected the UPDRS part III at baseline (V0), 12 months (V1), and 24 months (V2). Factor analysis and effect size using Cohen's d formula were performed in the Off and On states at V0, V1, and V2. RESULTS: We included 667 patients with PD, mean age of 62.59 ± 8.91 years, 410 (60.2%) males, with a median HY stage of 2.00 (1.00; 4.00) at baseline. Over time, the most discriminating items were postural stability and body bradykinesia ("arise from chair" and "gait") in the Off state, right and left upper extremity bradykinesia ("finger tap", "hand movements" and "prono/supination") in the On state. Body bradykinesia and right-left finger tapping were the items with the largest effect size (0.93, 0.84, 0.83, respectively) to assess motor improvement after receiving antiparkinsonian medications over time. CONCLUSION: Under specific circumstances, selecting a few items of the UPDRS part III, including postural stability, body bradykinesia, and upper extremity bradykinesia, could be used to create a quick clinical judgment of motor status and improvement in PD.

The Role of the PAA1 Gene on Melatonin Biosynthesis in Saccharomyces cerevisiae: A Search of New Arylalkylamine N-Acetyltransferases.

Recently, the presence of melatonin in fermented beverages has been correlated with yeast metabolism during alcoholic fermentation. Melatonin, originally considered a unique product of the pineal gland of vertebrates, has been also identified in a wide range of invertebrates, plants, bacteria, and fungi in the last two decades. These findings bring the challenge of studying the function of melatonin in yeasts and the mechanisms underlying its synthesis. However, the necessary information to improve the selection and production of this interesting molecule in fermented beverages is to disclose the genes involved in the metabolic pathway. So far, only one gene has been proposed as involved in melatonin production in Saccharomyces cerevisiae, PAA1, a polyamine acetyltransferase, a homolog of the vertebrate's aralkylamine N-acetyltransferase (AANAT). In this study, we assessed the in vivo function of PAA1 by evaluating the bioconversion of the different possible substrates, such as 5-methoxytryptamine, tryptamine, and serotonin, using different protein expression platforms. Moreover, we expanded the search for new N-acetyltransferase candidates by combining a global transcriptome analysis and the use of powerful bioinformatic tools to predict similar domains to AANAT in S. cerevisiae. The AANAT activity of the candidate genes was validated by their overexpression in E. coli because, curiously, this system evidenced higher differences than the overexpression in their own host S. cerevisiae. Our results confirm that PAA1 possesses the ability to acetylate different aralkylamines, but AANAT activity does not seem to be the main acetylation activity. Moreover, we also prove that Paa1p is not the only enzyme with this AANAT activity. Our search of new genes detected HPA2 as a new arylalkylamine N-acetyltransferase in S. cerevisiae. This is the first report that clearly proves the involvement of this enzyme in AANAT activity.

Stepwise application of ECG and electrogram-based criteria to ensure electrical resynchronization with left bundle branch pacing.

AIMS: To define a stepwise application of left bundle branch pacing (LBBP) criteria that will simplify implantation and guarantee electrical resynchronization. Left bundle branch pacing has emerged as an alternative to biventricular pacing. However, a systematic stepwise criterion to ensure electrical resynchronization is lacking. METHODS AND RESULTS: A cohort of 24 patients from the LEVEL-AT trial (NCT04054895) who received LBBP and had electrocardiographic imaging (ECGI) at 45 days post-implant were included. The usefulness of ECG- and electrogram-based criteria to predict accurate electrical resynchronization with LBBP were analyzed. A two-step approach was developed. The gold standard used to confirm resynchronization was the change in ventricular activation pattern and shortening in left ventricular activation time, assessed by ECGI. Twenty-two (91.6%) patients showed electrical resynchronization on ECGI. All patients fulfilled pre-screwing requisites: lead in septal position in left-oblique projection and W paced morphology in V1. In the first step, presence of either right bundle branch conduction delay pattern (qR or rSR in V1) or left bundle branch capture Plus (QRS ≤120 ms) resulted in 95% sensitivity and 100% specificity to predict LBBP resynchronization, with an accuracy of 95.8%. In the second step, the presence of selective capture (100% specificity, only 41% sensitivity) or a spike-R <80 ms in non-selective capture (100% specificity, sensitivity 46%) ensured 100% accuracy to predict resynchronization with LBBP. CONCLUSION: Stepwise application of ECG and electrogram criteria may provide an accurate assessment of electrical resynchronization with LBBP (Graphical abstract).

Evolution of Deceleration Zones During Ventricular Tachycardia Ablation and Relation With Cardiac Magnetic Resonance.

BACKGROUND: A new functional mapping strategy based on targeting deceleration zones (DZs) has become one of the most commonly used strategies within the armamentarium of substrate-based ablation methods for ventricular tachycardia (VT) in patients with structural heart disease. The classic conduction channels detected by voltage mapping can be accurately determined by cardiac magnetic resonance (CMR). OBJECTIVES: The purpose of this study was to analyze the evolution of DZs during ablation and their correlation with CMR. METHODS: Forty-two consecutive patients with scar-related VT undergoing ablation after CMR in Hospital Clinic (October 2018-December 2020) were included (median age 65.3 ± 11.8 years; 94.7% male; 73.7% ischemic heart disease). Baseline DZs and their evolution in isochronal late activation remaps were analyzed. A comparison between DZs and CMR conducting channels (CMR-CCs) was realized. Patients were prospectively followed for VT recurrence for 1 year. RESULTS: Overall, 95 DZs were analyzed, 93.68% of which were correlated with CMR-CCs: 44.8% located in the middle segment and 55.2% located in the entrance/exit of the channel. Remapping was performed in 91.7% of patients (1 remap: 33.3%, 2 remaps: 55.6%, and 3 remaps: 2.8%). Regarding the evolution of DZs, 72.2% disappeared after the first ablation set, with 14.13% not ablated at the end of the procedure. A total of 32.5% of DZs in remaps correlated with a CMR-CCs already detected, and 17.5% were associated with an unmasked CMR-CCs. One-year VT recurrence was 22.9%. CONCLUSIONS: DZs are highly correlated with CMR-CCs. In addition, remapping can lead to the identification of hidden substrate initially not identified by electroanatomic mapping but detected by CMR.

Management of Ventricular Arrhythmias in Heart Failure.

PURPOSE OF REVIEW: Despite substantial progress in medical and device-based heart failure (HF) therapy, ventricular arrhythmias (VA) and sudden cardiac death (SCD) remain a major challenge. Here we review contemporary management of VA in the context of HF with one particular focus on recent advances in imaging and catheter ablation. RECENT FINDINGS: Besides limited efficacy of antiarrhythmic drugs (AADs), their potentially life-threatening side effects are increasingly acknowledged. On the other hand, with tremendous advances in catheter technology, electroanatomical mapping, imaging, and understanding of arrhythmia mechanisms, catheter ablation has evolved into a safe, efficacious therapy. In fact, recent randomized trials support early catheter ablation, demonstrating superiority over AAD. Importantly, CMR imaging with gadolinium contrast has emerged as a central tool for the management of VA complicating HF: CMR is not only essential for an accurate diagnosis of the underlying entity and subsequent treatment decisions, but also improves risk stratification for SCD prevention and patient selection for ICD therapy. Finally, 3-dimensional characterization of arrhythmogenic substrate by CMR and imaging-guided ablation approaches substantially enhance procedural safety and efficacy. VA management in HF patients is highly complex and should be addressed in a multidisciplinary approach, preferably at specialized centers. While recent evidence supports early catheter ablation of VA, an impact on mortality remains to be demonstrated. Moreover, risk stratification for ICD therapy may have to be reconsidered, taking into account imaging, genetic testing, and other parameters beyond left ventricular function.

[Usefulness of artery femoral ultrasound complementary to carotid exploration for the detection of subclinical atheromatosis in patients with human immunodeficiency virus infection]. / Utilidad de la ecografía de la arteria femoral complementaria a la exploración carotídea para la detección de ateromatosis subclínica en pacientes con infección por el virus de la inmunodeficiencia humana.

INTRODUCTION: Detection of subclinical atheromatosis disease (SAD) in patients with human immunodeficiency virus (HIV) infection is usually based on carotid ultrasound. However, studies in other pathologies have shown a probable underestimation of SAD when its detection is exclusively based on carotid exploration. This study evaluates the impact on detection of SAD in patients with HIV through combined carotid and femoral exploration. METHODS: Cross-sectional and prospective study of patients with HIV, diagnosed between 2008-2017. Carotid and femoral ultrasound examination was performed in all patients. EAS was defined according to Mannheim criteria. RESULTS: One hundred two patients were included (mean age: 40 years, 73.5% being male). The prevalence of carotid SAD in the total sample was 15.7% (n=16), and the prevalence of femoral SAD was 18.6% (n=19). The proportion of patients with global SAD criteria (carotid or femoral) was 23.5% (n=24), which implies an absolute increase in SAD detection of 7.84% (95% CI; 2.63-13.06%) at the total sample. CONCLUSIONS: Detection of SAD is significantly increased by the combined use of carotid and femoral arterial ultrasound in the population affected by HIV infection.

Association Between Insulin-Like Growth Factor-1 and Social Cognition in Huntington's Disease.

Background: Insulin-like growth factor 1 (IGF-1) seems to be involved in the neural circuits associated with social cognition and brain structure. Objectives: To investigate the association of IGF-1 levels with social cognition and brain structure in Huntington's disease (HD). Methods: We evaluated social cognition using the Ekman test in 22 HD patients and 19 matched controls. Brain structure was assessed using standard volume-based voxel-based morphometry and surface-based cortical thickness pipeline. We analyzed the association of IGF-1 levels with social cognition and brain structure using adjusted regression analysis. Results: Social cognition was worse in HD patients (P < 0.001), on antidopaminergic drugs (P = 0.02), and with lower IGF-1 levels (P = 0.04). In neuroimaging analyses, lower IGF-1 levels were associated with social cognition impairment and atrophy mainly in frontotemporal regions (P < 0.05 corrected). Conclusions: In HD, abnormal IGF-1 function seems to be associated with brain atrophy leading to clinical deficits in social cognition.

Scar conducting channel characterization to predict arrhythmogenicity during ventricular tachycardia ablation.

AIMS: Heterogeneous tissue channels (HTCs) detected by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) are related to ventricular arrhythmias, but there are few published data about their arrhythmogenic characteristics. METHODS AND RESULTS: We enrolled 34 consecutive patients with ischaemic and non-ischaemic cardiomyopathy who were referred for ventricular tachycardia (VT) ablation. LGE-CMR was performed prior to ablation, and the HTCs were analyzed. Arrhythmogenic HTCs linked to induced VT were identified during the VT ablation procedure. The characteristics of arrhythmogenic HTCs were compared with those of non-arrhythmogenic HTCs. Three patients were excluded due to low-quality LGE-CMR images. A total of 87 HTCs were identified on LGE-CMR in 31 patients (age:63.8 ± 12.3 years; 96.8% male; left ventricular ejection fraction: 36.1 ± 10.7%). Of the 87 HTCs, only 31 were considered arrhythmogenic because of their relation to a VT isthmus. The HTCs related to a VT isthmus were longer [64.6 ± 49.4 vs. 32.9 ± 26.6 mm; OR: 1.02; 95% CI: (1.01-1.04); P < 0.001] and had greater mass [2.5 ± 2.2 vs. 1.2 ± 1.2 grams; OR: 1.62; 95% CI: (1.18-2.21); P < 0.001], a higher degree of protectedness [26.19 ± 19.2 vs. 10.74 ± 8.4; OR 1.09; 95% CI: (1.04-1.14); P < 0.001], higher transmurality [number of wall layers with CCs: 3.8 ± 2.4 vs. 2.4 ± 2.0; OR: 1.31; 95% CI: (1.07-1.60); P = 0.008] and more ramifications [3.8 ± 2.0 vs. 2.7 ± 1.1; OR: 1.59; 95% CI: (1.15-2.19); P = 0.002] than non-arrhythmogenic HTCs. Multivariate logistic regression analysis revealed that protectedness was the strongest predictor of arrhythmogenicity. CONCLUSION: The protectedness of an HTC identified by LGE-CMR is strongly related to its arrhythmogenicity during VT ablation.