The pediatric DAV-expert algorithm: A GAVeCeLT/GAVePed consensus for the choice of the most appropriate venous access device in children.

In pediatric patients, the choice of the venous access device currently relies upon the operator's experience and preference and on the local availability of specific resources and technologies. Though, considering the limited options for venous access in children if compared to adults, such clinical choice has a great critical relevance and should preferably be based on the best available evidence. Though some algorithms have been published over the last 5 years, none of them seems fully satisfactory and useful in clinical practice. Thus, the GAVePed-which is the pediatric interest group of the most important Italian group on venous access, GAVeCeLT-has developed a national consensus about the choice of the venous access device in children. After a systematic review of the available evidence, the panel of the consensus (which included Italian experts with documented competence in this area) has provided structured recommendations answering 10 key questions regarding the choice of venous access both in emergency and in elective situations, both in the hospitalized and in the non-hospitalized child. Only statements reaching a complete agreement were included in the final recommendations. All recommendations were also structured as a simple visual algorithm, so as to be easily translated into clinical practice.

Caliber of the deep veins of the arm in infants and neonates: The VEEIN study (Vascular Echography Evaluation in Infants and Neonates).

PURPOSE: Ultrasound-guided peripherally inserted central catheters (PICCs) are increasingly used in children, though their insertion may be limited by the small caliber of the deep veins of the arm. Previous studies have suggested to use age or weight as a guide to the feasibility of PICC insertion. We have planned an observational study with the purpose of identifying the actual feasibility of PICC insertion based on the ultrasound evaluation of the deep veins of the arm in groups of children of different weight range. METHODS: We have studied 252 children weighing between 2.5 and 20 kg, divided in five different groups (group 1: 2.5-4 kg; group 2: 4.1-7 kg; group 3: 7.1-10 kg; group 4: 10.1-15 kg; group 5: 15.1-20 kg): the caliber of brachial vein, basilic vein, and cephalic vein at mid-upper arm + the caliber of the axillary vein at the axilla were measured by ultrasound scan. RESULTS: Veins of caliber >3 mm (appropriate for insertion of a 3 Fr non-tunneled PICC) were found at mid-upper arm in no child of group 1 or 2, in 13% of group 3, in 28% of group 4, and in 54% of group 5. An axillary vein >3 mm (appropriate for insertion of a 3 Fr tunneled PICC) were found in 5.8% of group 1, 30.6% of group 2, 67% of group 3, 82% of group 4, and 94% of group 5. CONCLUSIONS: The age and the weight of the child have a small role in predicting the caliber of the veins of the arm. Veins should be measured case by case through a proper and systematic ultrasound evaluation; however, the clinician can expect that insertion of a 3 Fr PICC may be feasible in one third of children weighing between 4 and 7 kg, and in most children weighing more than 7 kg, especially if adopting the tunneling technique.

Filamin-C variant-associated cardiomyopathy: A pooled analysis of individual patient data to evaluate the clinical profile and risk of sudden cardiac death.

BACKGROUND: Mutations in filamin-C (FLNC) are involved in the pathogenesis of arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy (DCM), and have been associated with a left ventricular (LV) phenotype, characterized by nonischemic LV fibrosis, ventricular arrhythmias, and sudden cardiac death (SCD). OBJECTIVE: The purpose of this study was to investigate the prevalence of FLNC variants in a gene-negative ACM population and to evaluate the clinical phenotype and SCD risk factors in FLNC-associated cardiomyopathies. METHODS: ACM probands who tested negative for mutations in ACM-related genes underwent FLNC genetic screening. Clinical and genetic data were collected and pooled together with those of previously published FLNC-ACM and FLNC-DCM patients. RESULTS: In a cohort of 270 gene-elusive ACM probands, 12 (4.4%) had FLNC variants, and 13 additional family members carried the same mutation. Eighteen FLNC variant carriers (72%) had a diagnosis of ACM (72% male; mean age 45 years). On pooled analysis, 145 patients with FLNC-associated cardiomyopathies were included. Electrocardiographic (ECG) low QRS voltages were detected in 37%, and T-wave inversion (TWI) in inferolateral/lateral leads in 24%. Among 67 patients who had cardiac magnetic resonance (CMR), LV nonischemic late gadolinium enhancement (LGE) was found in 75%. SCD occurred in 28 patients (19%), 15 of whom showed LV nonischemic LGE/fibrosis. Compared with patients with no SCD, those who experienced SCD more frequently had inferolateral/lateral TWI (P = .013) and LV LGE/fibrosis (P = .033). CONCLUSION: Clinical phenotype of FLNC cardiomyopathies is characterized by late-onset presentation and typical ECG and CMR features. SCD is associated with the presence of LV LGE/fibrosis but not with severe LV systolic dysfunction.

Potential role of a subcutaneously anchored securement device in preventing dislodgment of tunneled-cuffed central venous devices in pediatric patients.

INTRODUCTION: The potential drawbacks of tunneled-cuffed catheters are complications such as local or systemic infection, dislodgment, rupture, malfunction, and deep venous thrombosis. Aim of this study is to describe the incidence of complications, focusing on dislodgment and on the role of new securement devices in reducing this annoying issue. METHODS: We enrolled all pediatric patients with tunneled-cuffed central venous catheters (CVCs) inserted at the Giannina Gaslini Institute during a 16-month period. Demographic data, technical details, intraoperative and postoperative complications were recorded and stored in a digital database according to Data Protection Act. RESULTS: During the study period, we collected 173 tunneled-cuffed CVCs. All but three insertions were successful. There were 50 complications involving 47 CVCs. Complications included 13 infections, 27 dislodgments, 4 thromboses, 3 obstructions, and 3 malfunctions/breaking. In 51 of 173 CVCs, we used subcutaneously anchored securement device (SAS). CONCLUSIONS: The use of SAS proved to significantly reduce the incidence of complications in pediatric patients, particularly during the first 30 postoperative days. Basing on our results we suggest to routinely adopt this new securement device for high-risk CVC.

Atypical use of PICC in infants and small children: a unicentric experience.

INTRODUCTION: The peripherally inserted central catheters (PICCs) are vascular access devices (VAD) that are increasingly being used in the pediatric population. If a small vein caliber prevents positioning the catheter in the arm, the following step is to position the same catheter in the supraclavicular area, which can be defined as an off-label use or "atypical" approach, first described by Pittiruti. MATERIALS AND METHODS: We retrospectively reviewed PICC positioning with puncture-site in the supra-clavicular area ("atypical" PICC insertion) and then tunneled on the chest. RESULTS: Nineteen atypical PICCs were positioned in 18 patients. The median age of patients at the day of implant was 14 months (IQR 3-27 months), and weight 7.5 kg (IQR 4-12 kg). Within this population, 74% of cases scheduled for a typical PICC insertion presented vein caliber too small for this procedure. For this reason, the typical PICC insertion was changed in favor of an atypical PICC procedure. Atypical PICCs were successfully used in 100% of cases without immediate complications. CONCLUSIONS: Atypical PICC positioning is a safe and useful alternative to the conventional technique when there is need for a central vascular access device (CVAD) for mid- or long-term therapy.

Brachiocephalic vein for percutaneous ultrasound-guided central line positioning in children: A 20-month preliminary experience with 109 procedures.

BACKGROUND: Ultrasound-guided (USG) cannulation of the brachiocephalic vein (BCV) is gaining worldwide consensus for central venous access in children. This study reports a 20-month experience with this approach in children. METHODS: All patients who underwent percutaneous USG central venous catheter (CVC) positioning in the BCV between August 2013 and March 2015 have been included. Devices inserted during this period were open-ended, either single or double-lumen tunneled CVC. Our series was divided into three consecutive study periods in order to determine the relative incidence of repositioning and complications. RESULTS: During the study period, a total of 95 patients underwent 109 CVC insertions in the BCV. The median length of CVC duration was 230 days for a total of 23,212 catheter days. No major intraoperative complications occurred. Overall rate of CVC-related postoperative complications requiring repositioning or precocious removal was 0.90 per 1,000 catheter days and involved 21 CVC (19%, 95% confidence interval 13-28). These included 18 dislodgments, two infections, and one malfunction. Double-lumen CVCs represented the only significant risk factor for complications (52% complications-three per 1,000 catheter days). CONCLUSION: USG supraclavicular cannulation of the BCV represents a safe approach for central line placement in children. It proved to be versatile, as it can be used in premature infants as well as in adolescents. Provided it is adopted by operators experienced in USG cannulation, we strongly suggest to resort to this approach as a first-line choice in children undergoing tunnelled central line placement for long-lasting therapy.

Prognostic value of endocardial voltage mapping in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia.

BACKGROUND: Endocardial voltage mapping (EVM) identifies low-voltage right ventricular (RV) areas, which may represent the electroanatomic scar substrate of life-threatening tachyarrhythmias. We prospectively assessed the prognostic value of EVM in a consecutive series of patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). METHODS AND RESULTS: We studied 69 consecutive ARVC/D patients (47 males; median age 35 years [28-45]) who underwent electrophysiological study and both bipolar and unipolar EVM. The extent of confluent bipolar (<1.5 mV) and unipolar (<6.0 mV) low-voltage electrograms was estimated using the CARTO-incorporated area calculation software. Fifty-three patients (77%) showed ≥1 RV electroanatomic scars with an estimated burden of bipolar versus unipolar low-voltage areas of 24.8% (7.2-31.5) and 64.8% (39.8-95.3), respectively (P=0.009). In the remaining patients with normal bipolar EVM (n=16; 23%), the use of unipolar EVM unmasked ≥1 region of low-voltage electrogram affecting 26.2% (11.6-38.2) of RV wall. During a median follow-up of 41 (28-56) months, 19 (27.5%) patients experienced arrhythmic events, such as sudden death (n=1), appropriate implantable cardioverter defibrillator interventions (n=7), or sustained ventricular tachycardia (n=11). Univariate predictors of arrhythmic outcome included previous cardiac arrest or syncope (hazard ratio=3.4; 95% confidence interval, 1.4-8.8; P=0.03) and extent of bipolar low-voltage areas (hazard ratio=1.7 per 5%; 95% confidence interval, 1.5-2; P<0.001), whereas the only independent predictor was the bipolar low-voltage electrogram burden (hazard ratio=1.6 per 5%; 95% confidence interval, 1.2-1.9; P<0.001). Patients with normal bipolar EVM had an uneventful clinical course. CONCLUSIONS: The extent of bipolar RV endocardial low-voltage area was a powerful predictor of arrhythmic outcome in ARVC/D, independently of history and RV dilatation/dysfunction. A normal bipolar EVM characterized a low-risk subgroup of ARVC/D patients.

Prophylactic implantable defibrillator in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior ventricular fibrillation or sustained ventricular tachycardia.

BACKGROUND: The role of implantable cardioverter-defibrillator (ICD) in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior ventricular fibrillation (VF) or sustained ventricular tachycardia is an unsolved issue. METHODS AND RESULTS: We studied 106 consecutive patients (62 men and 44 women; age, 35.6±18 years) with arrhythmogenic right ventricular cardiomyopathy/dysplasia who received an ICD based on 1 or more arrhythmic risk factors such as syncope, nonsustained ventricular tachycardia, familial sudden death, and inducibility at programmed ventricular stimulation. During follow-up of 58±35 months, 25 patients (24%) had appropriate ICD interventions and 17 (16%) had shocks for life-threatening VF or ventricular flutter. At 48 months, the actual survival rate was 100% compared with the VF/ventricular flutter-free survival rate of 77% (log-rank P=0.01). Syncope significantly predicted any appropriate ICD interventions (hazard ratio, 2.94; 95% confidence interval, 1.83 to 4.67; P=0.013) and shocks for VF/ventricular flutter (hazard ratio, 3.16; 95% confidence interval, 1.39 to 5.63; P=0.005). The positive predictive value of programmed ventricular stimulation was 35% for any appropriate ICD intervention and 20% for shocks for VF/ventricular flutter, with a negative predictive value of 70% and 74%. None of the 27 asymptomatic patients with isolated familial sudden death had appropriate ICD therapy. Twenty patients (19%) had inappropriate ICD interventions, and 18 (17%) had device-related complications. CONCLUSIONS: One fourth of patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior sustained ventricular tachycardia or VF had appropriate ICD interventions. Syncope was an important predictor of life-saving ICD intervention and is an indication for ICD. Prophylactic ICD may not be indicated in asymptomatic patients because of their low arrhythmic risk regardless of familial sudden death and programmed ventricular stimulation findings. Programmed ventricular stimulation had a low predictive accuracy for ICD therapy.

Clinical predictors of termination and clinical outcome of catheter ablation for persistent atrial fibrillation.

OBJECTIVES: This study evaluated the role of pre-procedural clinical variables to predict procedural and clinical outcomes of catheter ablation in patients with long-lasting persistent atrial fibrillation (AF). BACKGROUND: Catheter ablation of persistent AF remains a challenging task. METHODS: Catheter ablation was performed in 90 patients (76 men, age 57 +/- 11 years) with long-lasting persistent AF. The history of AF, echocardiographic parameters, presence of structural heart disease, and surface electrocardiogram (ECG) AF cycle length (CL) were assessed before ablation and analyzed with respect to procedural termination and clinical outcome. Mean follow-up was 28 +/- 4 months. RESULTS: Persistent AF was terminated in 76 of 90 patients (84%) by ablation. The duration of continuous AF was shorter (p < 0.0001), the surface ECG AFCL was longer (p < 0.0001), and the left atrium was smaller (p < 0.01) in patients in whom AF was terminated by catheter ablation. The surface ECG AFCL was the only independent predictor of AF termination (p < 0.01). Maintenance of sinus rhythm was associated with a shorter duration of continuous AF (p < 0.0001), a longer surface ECG AFCL (p < 0.001), and a smaller left atrium (p < 0.05) compared with those with recurrent arrhythmia. In multivariate analysis, the surface ECG AFCL and the AF duration predicted clinical success of persistent AF ablation (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: The surface ECG AFCL is a clinically useful pre-ablation tool for predicting patients in whom sinus rhythm can be restored by catheter ablation. The duration of continuous AF and the surface ECG AFCL are predictive of maintenance of sinus rhythm.

Sudden cardiac death in athletes: can it be prevented by screening?

In 1982, a nationwide program of preparticipation screening of all individuals embarking in competitive sports activity was launched in Italy. The screening protocol includes athlete's personal and family history, physical examination, and twelve-lead electrocardiogram (ECG) as first-line examination; additional tests such as echocardiography or exercise testing are requested only for subjects who have positive findings at the initial evaluation. This screening algorithm, which has been used for preparticipation evaluation of millions of Italian athletes over a period of > 25 years has provided adequate sensitivity and specificity for detection of athletes affected by potentially dangerous cardiomyopathy or arrhythmia at risk of athletic-field death and has led to substantial reduction of mortality of young competitive athletes (by approximately 90%), mostly by preventing sudden death from cardiomyopathy.

Left atrial linear lesions are required for successful treatment of persistent atrial fibrillation.

AIMS: This study evaluates the clinical outcome and incidence of left atrial (LA) macro re-entrant atrial tachycardia (AT) in patients in whom persistent atrial fibrillation (AF) terminated during catheter ablation without the need of roof and mitral lines. METHODS AND RESULTS: Persistent AF was terminated by ablation in 154 of 180 consecutive patients. AF history was 60 months including 11 months of continuous AF. Patients were divided into two groups: those who had not required both LA linear lesions to terminate AF (group A, 85 patients), and those who had (group B, 69 patients). There was no difference in clinical and echocardiographic characteristics between both groups except for a shorter duration of continuous AF in group A (9 vs.12 months, respectively) (P = 0.03). After 28 months of follow-up, the incidence of LA macro re-entrant AT necessitating linear ablation was higher in group A (76%) compared with group B (33%) (P = 0.002). When complete linear block could not be achieved during the index procedure, the incidence of subsequent roof (P = 0.008) or mitral isthmus (P = 0.010) dependent macro re-entrant AT was higher. CONCLUSION: Although persistent AF can be terminated by catheter ablation without linear lesions, the majority will require linear lesions for macro re-entrant AT.

Early recurrences after atrial fibrillation ablation: prognostic value and effect of early reablation.

INTRODUCTION: Early arrhythmia recurrences are common within the first month after atrial fibrillation (AF) ablation. The long-term consequences of these early recurrences (ER) are controversial. We investigated whether ER were predictive of late recurrences and the impact of early reablation on clinical outcome. METHODS: Three hundred two consecutive patients with paroxysmal or persistent AF were studied. Arrhythmia recurrence was defined as documented episode of AF or atrial tachycardia. Of 151 patients with ER, a subset of 61 patients had reablation within the first month following the index ablation (early reablation). In the remaining 90 patients, a repeat procedure was only performed for later arrhythmia recurrences occurring beyond 1 month. Patients were followed with clinical interview and ambulatory 24 hours monitoring. RESULTS: Patients with and without early reablation had similar baseline characteristics including echocardiographic parameters and type of AF. During a mean follow-up of 11 +/- 11 months, 82 patients (91%) without early reablation experienced late clinical recurrences. In contrast, patients with early reablation had lower rate of clinical recurrences (51% vs 91%, P < 0.0001) and fewer additional procedures (36% vs 91%, P < 0.0001). However, the total number of procedures over the entire follow-up was greater in those patients with early reablation (2.5 +/- 0.7 vs 2.2 +/- 0.6, P = 0.02). CONCLUSION: An overwhelming majority of patients with recurrences within the first month after ablation have late recurrences. An early reablation reduces the incidence of further recurrences. However, the overall number of procedures is higher in the medium-term follow-up. The optimal timing for the second procedure remains to be defined.

Insulin generates free radicals by an NAD(P)H, phosphatidylinositol 3'-kinase-dependent mechanism in human skin fibroblasts ex vivo.

Oxidative stress may be involved in the development of vascular complications associated with diabetes; however, the molecular mechanism responsible for increased production of free radicals in diabetes remains uncertain. Therefore, we examined whether acute hyperinsulinemia increases the production of free radicals and whether this condition affects proliferative extracellular signal-regulated kinase (ERK-1 and -2) signaling in human fibroblasts in vitro. Insulin treatment significantly increased intracellular superoxide anion (O(2)(-)) production, an effect completely abolished by Tiron, a cell-permeable superoxide dismutase (SOD) mimetic and by polyethylene glycol (PEG)-SOD, but not by PEG catalase. Furthermore, insulin-induced O(2)(-) production was attenuated by the NAD(P)H inhibitor apocynin, but not by rotenone or oxypurinol. Inhibition of the phosphatidylinositol 3'-kinase (PI 3'-kinase) pathway with LY294002 blocked insulin-stimulated O(2)(-) production, suggesting a direct involvement of PI 3'-kinase in the activation of NAD(P)H oxidase. The insulin-induced free radical production led to membranous translocation of p47phox and markedly enhanced ERK-1 and -2 activation in human fibroblasts. In conclusion, these findings provided direct evidence that elevated insulin levels generate O(2)(-) by an NAD(P)H-dependent mechanism that involves the activation of PI 3'-kinase and stimulates ERK-1- and ERK-2-dependent pathways. This effect of insulin may contribute to the pathogenesis and progression of cardiovascular disease in the insulin resistance syndrome.