Prospective Assessment of Late Conduction Recurrence Across Radiofrequency Lesions Producing Electrical Disconnection at the Pulmonary Vein Ostium in Patients With Atrial Fibrillation

Background— In patients with atrial fibrillation (AF) undergoing radiofrequency (RF) electrical disconnection of multiple pulmonary veins (PVs), the incidence of late conduction recurrences has not been systematically determined. Methods and Results— Using a prospectively designed, multistep approach, we aimed at assessing the correlation between acute achievement and chronic maintenance of electrical conduction block across RF lesions disconnecting the distal tract of the PV in 43 patients (52.3±8.2 years) with AF. Forty-one left superior (LS), 42 right superior (RS), 25 left inferior (LI), and 9 right inferior (RI) PVs were targeted during 108 EP procedures (2.6±0.5 per patient). Seventeen patients underwent 2 procedures, 23 patients underwent 3 procedures, and 3 patients underwent 4 procedures. During the first attempt, electrical disconnection was achieved in 112 PVs (95.7%). During a next procedure (time interval, 4.6±1.9 months), conduction recurrence was observed in 32 of 39 LSPVs (82.1%), 29 of 40 RSPVs (72.5%), 20 of 24 LIPVs (83.3%), and 7 of 9 RIPV (77.8%). After reablation at gap sites, a later procedure (time interval, 5.1±2.4 months) revealed a second recurrence in 13 of 22 LSPVs (59.1%) and 14 of 19 RSPVs (73.7%). Conclusions— Conduction recurrence across disconnecting RF lesions can be observed in ≈80% of cases 4 months after ablation. After reablation, similar recurrence rates are observed 5 months later. This high rate of late conduction recurrence may contribute significantly to AF recurrence in patients undergoing catheter ablation aiming at disconnection of multiple PVs

Clinical efficacy of ivabradine in patients with inappropriate sinus tachycardia: a prospective, randomized, placebo-controlled, double-blind, crossover evaluation

Objectives The purpose of this study was to investigate the role of ivabradine in the treatment of symptomatic inappropriate sinus tachycardia using a double-blind, placebo-controlled, crossover design. Background Due to its If blocking properties, ivabradine can selectively attenuate the high discharge rate from sinus node cells, causing inappropriate sinus tachycardia. Methods Twenty-one patients were randomized to receive placebo (n = 10) or ivabradine 5 mg twice daily (n = 11) for 6 weeks. After a washout period, patients crossed over for an additional 6 weeks. Each patient underwent symptom evaluation and heart rate assessment at the start and finish of each phase. Results After taking ivabradine, patients reported elimination of >70% of symptoms (relative risk: 0.25; 95% CI: 0.18 to 0.34; p < 0.001), with 47% of them experiencing complete elimination. These effects were associated with a significant reduction of heart rate at rest (from 88 ± 11 beats/min to 76 ± 11 beats/min, p = 0.011), on standing (from 108 ± 12 beats/min to 92 ± 11 beats/min, p < 0.0001), during 24 h (from 88 ± 5 beats/min to 77 ± 9 beats/min, p = 0.001), and during effort (from 176 ± 17 beats/min to 158 ± 16 beats/min, p = 0.001). Ivabradine administration was also associated with a significant increase in exercise performance. No cardiovascular side effects were observed in any patients while taking ivabradine. Conclusions In this cohort, ivabradine significantly improved symptoms associated with inappropriate sinus tachycardia and completely eliminated them in approximately half of the patients. These findings suggest that ivabradine may be an important agent for improving symptoms in patients with inappropriate sinus tachycardia

Effect of Size and Heterogeneity of Samples on Biomarker Discovery: Synthetic and Real Data Assessment

MOTIVATION: The identification of robust lists of molecular biomarkers related to a disease is a fundamental step for early diagnosis and treatment. However, methodologies for the discovery of biomarkers using microarray data often provide results with limited overlap. These differences are imputable to 1) dataset size (few subjects with respect to the number of features); 2) heterogeneity of the disease; 3) heterogeneity of experimental protocols and computational pipelines employed in the analysis. In this paper, we focus on the first two issues and assess, both on simulated (through an in silico regulation network model) and real clinical datasets, the consistency of candidate biomarkers provided by a number of different methods. METHODS: We extensively simulated the effect of heterogeneity characteristic of complex diseases on different sets of microarray data. Heterogeneity was reproduced by simulating both intrinsic variability of the population and the alteration of regulatory mechanisms. Population variability was simulated by modeling evolution of a pool of subjects; then, a subset of them underwent alterations in regulatory mechanisms so as to mimic the disease state. RESULTS: The simulated data allowed us to outline advantages and drawbacks of different methods across multiple studies and varying number of samples and to evaluate precision of feature selection on a benchmark with known biomarkers. Although comparable classification accuracy was reached by different methods, the use of external cross-validation loops is helpful in finding features with a higher degree of precision and stability. Application to real data confirmed these results

Prime esperienze di analisi computerizzata dei dati in corso di studio elettrofisiologico endocavitario clinico

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