Type I/II interferon in HIV-1-infected patients: expression in gut mucosa and in peripheral blood mononuclear cells and its modification upon probiotic supplementation

Expression of type I and II interferon (IFN) was evaluated in gut-associated lymphoid tissue (GALT) and peripheral blood mononuclear cells (PBMCs) of HIV-1-positive patients on long-term, suppressive, antiretroviral therapy before and after probiotic supplementation. IFNα subtypes and IFNβ were expressed at higher levels in GALT compared to PBMC, whereas an opposite trend of expression was recorded for IFNγ. An increase of IFNα6, IFNα10, IFNα14, IFNα17, and IFNα21 and a decrease of IFNγ were observed in both anatomical sites after probiotic supplementation

Silent Myocardial Ischemia and Late Ventricular Repolarization in the Genesis of Ventricular Fibrillation in Humans

Background We report a well-documented case of a patient, a 62-year-old man, with severe and asymptomatic left main coronary artery disease who had several episodes of silent myocardial ischemia and a syncopal attack during Holter recording. Methods and Results Ambulatory monitoring showed isolated giant U waves separated from the T wave 60 minutes before syncope that was due to reversible ventricular fibrillation lasting about 4 minutes and spontaneously reverting to asystole (7 seconds) and then to atrial fibrillation Conclusion Our experience suggests that myocardial ischemia may differently affect the repolarization times within the myocardium leading to widely disparate repolarization gradients that may represent the arrhythmogenic substrate for the occurrence of life-threatening ventricular tachyarrhythmias. A.N.E. 1999; 4(2):250–25

Left atrial tachycardia after circumferential pulmonary vein ablation for atrial fibrillation Electroanatomic characterization and treatment

ObjectivesThe purpose of this study was to evaluate the electroanatomic characteristics of left atrial tachycardia (AT) in a series of patients who underwent circumferential pulmonary vein ablation (CPVA) and to describe the ablation strategy and clinical outcome.BackgroundCircumferential pulmonary vein ablation is an effective treatment for atrial fibrillation. A potential midterm complication is the development of left AT. There are only isolated reports describing mapping and ablation of such arrhythmias.MethodsThirteen patients (age 57.4 ± 8.9 years, five female) underwent mapping and ablation of 14 left ATs via an electroanatomic mapping system a mean of 2.6 ± 1.6 months after CPVA.ResultsThree patients were characterized as having focal AT (cycle length: 266 ± 35.9 ms). Of 11 macro–re-entrant tachycardias studied in the remaining 10 patients (cycle length: 275 ± 75 ms), 5 showed single-loop and 6 dual-loop circuits. Re-entrant circuits used the mitral isthmus, the posterior wall, or gaps on previous encircling lines. Such gaps and all three foci occurred anterior to the left superior pulmonary vein or at the septal aspect of the right pulmonary veins. Thirteen of 14 tachycardias (93%) were successfully ablated.ConclusionsLeft AT after CPVA can be due to a macro–re-entrant or focal mechanism. Re-entry occurs most commonly across the mitral isthmus, the posterior wall, or gaps on previous ablation lines. Such gaps and foci occur most commonly at the anterior aspect of the left superior pulmonary vein and at the septal aspect of the right pulmonary veins. These arrhythmias can be successfully mapped and ablated with an electroanatomic mapping system

The Natural History of Asymptomatic Ventricular Pre-Excitation A Long-Term Prospective Follow-Up Study of 184 Asymptomatic Children

ObjectivesThe aim of this study was to describe the natural history of asymptomatic ventricular pre-excitation in children and to determine predictors of potentially life-threatening arrhythmic events.BackgroundSudden death can be the first clinical manifestation in asymptomatic children with ventricular pre-excitation, but reduction of its incidence by prophylactic ablation requires the identification of subjects at high risk.MethodsBetween 1995 and 2005 we prospectively collected clinical and electrophysiologic data from 184 children (66% male; median age 10 years; range 8 to 12 years) with asymptomatic ventricular pre-excitation on the electrocardiogram. After electrophysiologic testing, subjects were followed as outpatients taking no medications. The primary end point of the study was the occurrence of arrhythmic events. Predictors of potentially life-threatening arrhythmias were analyzed.ResultsOver a median follow-up of 57 months (min/max 32/90 months) after electrophysiologic testing, 133 children (mean age 10 years; range 8 to 12 years) did not experience arrhythmic events, remaining totally asymptomatic, while 51 children had within 20 months (min/max 8/60 months) a first arrhythmic event, which was potentially life-threatening in 19 of them (mean age 10 years; range 10 to 14 years). Life-threatening tachyarrhythmias resulted in cardiac arrest (3 patients), syncope (3 patients), atypical symptoms (8 patients), or minimal symptoms (5 patients). Univariate analysis identified tachyarrhythmia inducibility (p < 0.001), anterograde refractory period of accessory pathways (APERP) ≤240 ms (p < 0.001), and multiple accessory pathways (p < 0.001) as risk factors for potentially life-threatening arrhythmic events. Independent predictors by multivariate analysis were APERP (p = 0.001) and multiple accessory pathway (p = 0.001).ConclusionsThese findings are potentially relevant in terms of early identification of high-risk asymptomatic children with ventricular pre-excitation. Subjects with short APERPs and multiple pathways are at higher risk of developing life-threatening arrhythmic events and are the best candidates for prophylactic ablation

Assessing the Malignant Ventricular Arrhythmic Substrate in Patients With Brugada Syndrome.

Background: Guidelines recommend the use of implanted cardioverter-defibrillators in patients with Brugada syndrome and induced ventricular tachyarrhythmias, but there is no evidence supporting it. Objectives: This prospective registry study was designed to explore clinical and electrophysiological predictors of malignant ventricular tachyarrhythmia inducibility in Brugada syndrome. Methods: A total of 191 consecutive selected patients with (group 1; n = 88) and without (group 2; n = 103) Brugada syndrome–related symptoms were prospectively enrolled in the registry. Patients underwent electrophysiological study and substrate mapping or ablation before and after ajmaline testing (1 mg/kg/5 min). Results: Overall, before ajmaline testing, 53.4% of patients had ventricular tachyarrhythmia inducibility, which was more frequent in group 1 (65.9%) than in group 2 (42.7%; p < 0.001). Regardless of clinical presentation, larger substrates with more fragmented long-duration ventricular potentials were found in patients with inducible arrhythmias than in patients without inducible arrhythmias (p < 0.001). One extrastimulus was used in more extensive substrates (median 13 cm2; p < 0.001), and ventricular fibrillation was the more frequently induced rhythm (p < 0.001). After ajmaline, patients without arrhythmia inducibility had arrhythmia inducibility without a difference in substrate characteristics between the 2 groups. The substrate size was the only independent predictor of inducibility (odds ratio: 4.51; 95% confidence interval: 2.51 to 8.09; p < 0.001). A substrate size of 4 cm2 best identified patients with inducible arrhythmias (area under the curve: 0.98; p < 0.001). Substrate ablation prevented ventricular tachyarrhythmia reinducibility. Conclusions: In Brugada syndrome dynamic substrate variability represents the pathophysiological basis of lethal ventricular tachyarrhythmias. Substrate size is independently associated with arrhythmia inducibility, and its determination after ajmaline identifies high-risk patients missed by clinical criteria. Substrate ablation is associated with electrocardiogram normalization and not arrhythmia reinducibility. (Epicardial Ablation in Brugada Syndrome [BRUGADA_I]; NCT02641431; Epicardial Ablation in Brugada Syndrome: An Extension Study of 200 BrS Patients; NCT03106701