Impaired flow-mediated dilation (FMD) is associated with cardiovascular risk factors and provides prognostic information. Despite the noninvasive nature of this technique, a major limitation to its widespread use is low reproducibility. The aim of this study was to evaluate impact of methodological standardization among different investigation sites on brachial artery FMD reproducibility. Seven Italian centers recruited 135 healthy volunteers, aged 20-60 years. FMD was assessed by high-resolution ultrasound equipped with a stereotactic probe-holding device. Certified sonographers recorded brachial artery scans at baseline (day 1a), 1 h after (day 1b), and 1 month later (day 30). Endothelium-independent vasodilation (EIVD) to sublingual glyceril-trinitrate was recorded at day 1 and day 30. FMD and EIVD were blindly evaluated at the coordinating center by an automated edge detection system. The intra-session (day 1a versus 1b) and inter-session (day 1a versus 30) coefficients of variation were calculated. FMD was not significantly (P = 0.91) different at day 1a, day 1b and day 30 (6.52 ± 2.9, 6.42 ± 3.1, 6.57 ± 2.8%, respectively). The FMD intra-session coefficient of variation was 9.9 ± 8.4% (from 7.6 to 11.9% across centers). The FMD inter-session coefficient of variation was 12.9 ± 11.6% (from 11.6 to 16.1% across centers). Inter-session coefficient of variation for EIDV was 19.7 ± 16.8%. This study shows a homogeneous coefficient of variation for FMD among different centers. The inter-session coefficient of variation was similar to the intra-session coefficient of variation, representing the intrinsic FMD variability. We demonstrate for the first time that rigorous and standardized procedure may provide reproducible FMD assessment to study endothelial function in multicenter clinical trials.

Transvenous lead extraction (TLE) is a complex invasive procedure and the experience of the operator and the team is a major determinant of procedural outcomes. Because of very limited data available on minimum procedural volumes to enable training and ongoing competency for TLEs, we performed a meta-analysis aimed at assessing the outcomes of TLE in the centres with low, medium, and high volume of procedures. Of the 280 papers initially retrieved until February 2013, 66 observational studies met inclusion criteria and were included in at least one stratified meta-analysis: 17 were prospective studies; 47 had a retrospective design; and 2 were defined ‘experience studies’. We included only articles published after the introduction of laser technique (year 1999). We divided the studies in low, medium, and high volume centres utilizing either the European Heart Rhythm Association (EHRA) or Lexicon classification criteria. When meta-analyses were carried out separately for the studies with larger and smaller sample sizes, either using EHRA or Lexicon classification criteria, no clear differences emerged in the combined rate of major complications or intraoperative deaths. In contrast, both minor complications and mortality at 30 days decreased as centre volume increased. In our meta-analysis of observational studies, patients who have been treated in higher volume centres have a lower probability of minor complications and death at 30 days regardless of the infection rate, length of lead duration, type of device, and type of extraction.