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Papers by Francesco Manguso

Journal of the American College of Cardiology, Jan 17, 2018

Guidelines recommend the use of implanted cardioverter-defibrillators in patients with Brugada sy... more Guidelines recommend the use of implanted cardioverter-defibrillators in patients with Brugada syndrome and induced ventricular tachyarrhythmias, but there is no evidence supporting it. This prospective registry study was designed to explore clinical and electrophysiological predictors of malignant ventricular tachyarrhythmia inducibility in Brugada syndrome. 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). 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 induc...

Circulation. Arrhythmia and electrophysiology, 2017

There is emerging evidence that localization and elimination of abnormal electric activity in the... more There is emerging evidence that localization and elimination of abnormal electric activity in the epicardial right ventricular outflow tract may be beneficial in patients with Brugada syndrome. A total of 135 symptomatic Brugada syndrome patients having implantable cardiac defibrillator were enrolled: 63 (group 1) having documented ventricular tachycardia (VT)/ventricular fibrillation (VF) and Brugada syndrome-related symptoms, and 72 (group 2) having inducible VT/VF without ECG documentation at the time of symptoms. About 27 patients of group 1 experienced multiple implantable cardiac defibrillator shocks for recurrent VT/VF episodes. Three-dimensional maps before and after ajmaline determined the arrhythmogenic electrophysiological substrate (AES) as characterized by prolonged fragmented ventricular potentials. Primary end point was identification and elimination of AES leading to ECG pattern normalization and VT/VF noninducibility. Extensive areas of AES were found in the right v...

Circulation: Arrhythmia and Electrophysiology, 2015

Background— Whether Brugada syndrome (BrS) depends on functional epicardial substrates, which may... more Background— Whether Brugada syndrome (BrS) depends on functional epicardial substrates, which may be definitively eliminated by radiofrequency ablation, remains unknown. Methods and Results— Patients with BrS underwent epicardial mapping to identify areas of abnormal electrograms as target for radiofrequency ablation. Substrate identification consisted in mapping right ventricle epicardial surface before and after flecainide (2 mg/kg per 10 minutes). After radiofrequency ablation, flecainide and remap confirmed elimination of abnormal substrate, BrS ECG pattern, and ventricular tachycardia/ventricular fibrillation inducibility. Flecainide testing was performed at each follow-up visits ≤6 months. Fourteen patients with BrS, median age 39 years (30.3–42.3) with implantable cardioverter–defibrillator were enrolled. Low-voltage areas (<1.5 mV) were commonly identified on the anterior right free wall and right ventricular outflow tract, which increased after flecainide from 17.6 cm 2 ...

Circulation. Arrhythmia and electrophysiology, 2011

Information on comparative outcome between radiofrequency catheter ablation (RFA) and antiarrhyth... more Information on comparative outcome between radiofrequency catheter ablation (RFA) and antiarrhythmic drugs (AADs) >1 year after randomization is important for clinical decision-making. A total of 198 patients (age, 56 ± 10 years) with paroxysmal atrial fibrillation were randomly assigned to RFA (99 patients) or to AADs (99 patients). We evaluated efficacy of RFA or AADs in a comparable 48-month follow-up period according to intention-to-treat analysis. Cardiac rhythm was assessed with daily transtelephonic transmissions. Quality of life was also analyzed. At 4 years, among the 99 patients first assigned to RFA, the procedure was repeated because of recurrent atrial fibrillation/atrial tachycardia in 27 patients (27.3%). Among the 99 patients randomly assigned to AADs, 87 (87.9%) crossed over to undergo RFA and 4 years after random assignment only 12 (12.1%) were in sinus rhythm with AAD alone without ablation. Despite the high level of crossovers, at 4 years the intention-to-trea...

Therapeutic Advances in Chronic Disease, 2014

The most common extra-intestinal manifestation in patients with inflammatory bowel disease (IBD) ... more The most common extra-intestinal manifestation in patients with inflammatory bowel disease (IBD) is articular involvement, with a prevalence ranging between 17% and 39%. It is frequently characterized by an involvement of the axial joints but may also be associated with peripheral arthritis. The target of therapy in the management of arthritis associated with IBD is to reduce the inflammation and prevent any disability and/or deformity. This requires active cooperation between gastroenterologist and rheumatologist. The treatment of axial involvement has focused on the combination of exercise with nonsteroidal anti-inflammatory drugs. Immunomodulators have been efficacious in patients with peripheral arthritis and other extra-intestinal manifestations, but they are not effective for the treatment of axial symptoms of spondylitis. Tumor necrosis factor (TNF) α inhibitors have been proven to be highly effective in the treatment of IBD patients which are steroid-dependent or refractory ...

Journal of Pediatric Gastroenterology and Nutrition, 2006

Objective: To assess the effectiveness of the combined use of fecal calprotectin (FC), anti-Sacch... more Objective: To assess the effectiveness of the combined use of fecal calprotectin (FC), anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear staining antineutrophil antibody (pANCA), small intestinal permeability test (IP), and bowel wall ultrasonography measurement (BWUS) in the diagnostic work-up of children with suspected inflammatory bowel disease (IBD). Methods: All children referred for initial assessment of possible IBD were eligible. Patients with symptoms or signs (right-lower quadrant mass, perianal disease, or hematochezia) mandating a complete work-up for IBD were excluded. All enrolled patients underwent a clinical, laboratory, radiographic, and endoscopic evaluation including biopsy examinations. The immunoglobulin (Ig)G and IgA ASCA, IgG pANCA, FC, IP, and BWUS were tested in all patients at the initial assessment. Results: A final diagnosis of IBD was made in 27 patients: 17 Crohn disease and 10 ulcerative colitis. Eighteen children had other gastrointestinal diagnoses (8 functional bowel disorders, 5 food allergy-mediated diseases, 4 infectious enterocolitis, 1 familial Mediterranean fever). In patients with simultaneous abnormal values of FC, BWUS, and ASCA/pANCA, the estimated probability of having IBD was 99.47%. Patients with negative results on all tests had a 0.69% of probability of IBD. Conclusions: The incorporation of noninvasive diagnostic tests into the initial diagnostic approach may avoid unnecessary invasive procedures and facilitate clinical decision-making when the diagnosis of IBD in children is initially uncertain. JPGN 42:9-15, 2006.

The Journal of Clinical Endocrinology & Metabolism, 2007

Context: To date, the metabolic effects of the long-term metformin administration in anovulatory ... more Context: To date, the metabolic effects of the long-term metformin administration in anovulatory patients with polycystic ovary syndrome (PCOS) are known, whereas few data are available on the effects of its suspension. Objective: The objective of the study was to evaluate the effects of metformin suspension on insulin sensitivity in PCOS patients. Design: This was a prospective, randomized, placebo-controlled study. Setting: The study was conducted at the University “Magna Graecia” of Catanzaro, Italy. Patients: Patients included 30 normal-weight anovulatory PCOS women and 10 age- and body mass index-matched healthy controls. Intervention: PCOS patients were randomized to receive 1700 mg daily metformin (metformin group) or placebo tables (placebo group) for 12 months, whereas no treatment was administered in healthy women (control group). Main Outcome Measures: Clinical, endocrine, and metabolic profile and clamp insulin sensitivity index were evaluated at study entry and after 6,...

The Journal of Clinical Endocrinology & Metabolism, 2007

Context: Polycystic ovary syndrome (PCOS) is an endocrine disease closely related to several risk... more Context: Polycystic ovary syndrome (PCOS) is an endocrine disease closely related to several risk factors for cardiovascular disease. An impaired cardiopulmonary functional capacity was previously demonstrated in PCOS women. No data regarding the effects of a structured exercise training (ET) program on cardiopulmonary functional capacity in PCOS women are available. Objective: Our objective was to evaluate the effects of a 3-month ET program on cardiopulmonary functional capacity in young PCOS women.

The Journal of Clinical Endocrinology & Metabolism, 2006

Context: Polycystic ovary syndrome (PCOS) is associated with early impairment of vascular structu... more Context: Polycystic ovary syndrome (PCOS) is associated with early impairment of vascular structure and a low-grade chronic inflammation. Aldosterone is a well-recognized cardiovascular risk (CVR) factor and is related to inflammatory processes. Objective: Our objective was to investigate serum aldosterone levels in PCOS and correlate them to some CVR factors and early atherosclerotic markers. Design and Setting: A prospective baseline-controlled clinical study was conducted at the University “Federico II” of Naples School of Medicine (Naples, Italy). Patients: Fifty PCOS women age- and body mass index-matched with 50 healthy women were enrolled. Mean Outcome Measures: Anthropometric, hormonal, and metabolic patterns, including plasma aldosterone, renin, and C-reactive protein, were measured in each subject. Intima-media thickness was also evaluated in each patient and control. Results: Aldosterone levels were significantly increased (P < 0.001) in PCOS compared with healthy wome...

The Journal of Clinical Endocrinology & Metabolism, 2005

Context: Although metformin has been shown to be effective in the treatment of anovulation in wom... more Context: Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients. Objective: The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS. Design: We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial. Setting: The study was conducted at the University “Magna Graecia” of Catanzaro, Catanzaro, Italy. Patients: One hundred nonobese primary infertile anovulatory women with PCOS participated. Interventions: We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each. Mean outcome measures: The main outcome measures were ovulation, pregnan...

The Journal of Clinical Endocrinology & Metabolism, 2005

Context: Recent data indicate that women affected by the polycystic ovary syndrome (PCOS) are at ... more Context: Recent data indicate that women affected by the polycystic ovary syndrome (PCOS) are at greater risk for cardiovascular disease and that metformin may improve the metabolic alterations in these patients.

The Journal of Clinical Endocrinology & Metabolism, 2006

Context: Insulin resistance is a feature of polycystic ovary syndrome (PCOS), and it is related t... more Context: Insulin resistance is a feature of polycystic ovary syndrome (PCOS), and it is related to mitochondrial function, particularly with maximal oxygen consumption (VO 2max). At the moment, no evaluation of cardiopulmonary functional capacity in young patients with PCOS has been performed.

Human Reproduction, 2005

BACKGROUND: There are few data in the literature regarding the utility of metfomin before and dur... more BACKGROUND: There are few data in the literature regarding the utility of metfomin before and during gonadotrophin administration in women with polycystic ovary syndrome (PCOS). The aim of the present study was to assess the effect of the pre-treatment and co-administration of metformin in infertile PCOS women treated with controlled ovarian stimulation (COS) followed by timed intercourse (TI) or intrauterine insemination (IUI). METHODS: Seventy insulin-resistant primary infertile women with PCOS were randomized to receive metformin cloridrate (850 mg twice daily; group A) or placebo tablets (two tablets daily; group B) for 3 months. Three trials of COS using highly purified urinary FSH (hpFSH) plus TI/IUI were performed. Number of ampoules of gonadotrophin used, duration of the ovarian stimulation, cycle cancellation, ovulation, pregnancy, abortion, live birth, mono-ovulatory cycles, multiple pregnancies and ovarian hyperstimulation syndrome (OHSS) rates were assessed. RESULTS: No difference between groups was detected in ovulation, cycle cancellation, pregnancy, abortion, live birth, multiple pregnancies and OHSS rates. The mono-ovulatory cycle rates were significantly (P = 0.002) more frequent in group A than in group B, whereas the days of stimulation for non-cancelled cycles and the number of vials of gonadotrophins used were significantly (P < 0.001) higher in group A than in group B. CONCLUSION: In insulin-resistant women with PCOS, metformin pre-treatment and co-administration with hpFSH increases the mono-ovulatory cycles.

Human Reproduction, 2005

BACKGROUND: In Italy, a recent law has imposed a ban on the fertilization of more than three oocy... more BACKGROUND: In Italy, a recent law has imposed a ban on the fertilization of more than three oocytes at one time, and all resulting embryos produced must be transferred simultaneously. The aim of the present controlled study was to assess the clinical feasibility and efficacy of the perifollicular vascularity assessment for oocyte selection in IVF cycles. METHODS: Fifty-four young primary infertile non-obese women (27 cases and 27 age-and BMI-matched controls) underwent IVF cycles. The choice of the oocytes to fertilize was performed according to perifollicular vascularization in the experimental group, whereas in the control group, the standard morphologic criteria alone were used. The dose of gonadotrophins used, the dominant follicles obtained, the duration of the ovarian stimulation, the number of oocytes retrieved, the number/quality of oocytes fertilized and of cleaved embryos, cycle cancellation, implantation, clinical pregnancy, ongoing pregnancy, multiple pregnancies and ovarian hyperstimulation syndrome rates were assessed in each group. RESULTS: The assessment of perifollicular vascularity was feasible in 88.9% of cases. No difference between groups was detected in any parameter evaluated. CONCLUSION: Power Doppler assessment of perifollicular vascularity seems to have no clinical utility for oocyte selection in IVF cycles for young infertile women.

Human Reproduction, 2005

BACKGROUND: Metformin has been shown to improve fertility in anovulatory patients with polycystic... more BACKGROUND: Metformin has been shown to improve fertility in anovulatory patients with polycystic ovary syndrome (PCOS), inducing not only a high ovulation and pregnancy rate but also reducing the incidence of miscarriages. The aim of the present study was to evaluate the uterine effects of metformin in patients with PCOS who ovulated under metformin. METHODS: Thirty-seven non-obese primary infertile anovulatory patients with PCOS and another 30 age-and body mass index-matched healthy women (control group) were studied. PCOS patients were treated with metformin (850 mg twice daily) for 6 months, whereas the control group did not receive any treatment. In these PCOS patients who ovulated whilst under metformin treatment (PCOS group) and in controls, uterine, sub-endometrial and endometrial blood flow, and endometrial thickness and pattern were evaluated using serial ultrasonographic assessments. RESULTS: Before treatment, uterine, sub-endometrial and endometrial blood flows were significantly lower in patients with PCOS than in the control group. All indexes of uterine vascularization were significantly improved in the PCOS group with metformin treatment and were not different from the controls. Nor was any difference in endometrial thickness and pattern detected between PCOS and control groups. After grouping the data of PCOS patients who ovulated under metformin for cycles with favourable/unfavourable reproductive outcome, no difference in any parameter was observed. CONCLUSIONS: Metformin improves all surrogate markers of endometrial receptivity in PCOS patients, without difference between patients who had favourable or unfavourable reproductive outcome.

European Heart Journal, 2009

To evaluate the prevalence, clinical significance, and prognosis of latent Brugada syndrome (BrS)... more To evaluate the prevalence, clinical significance, and prognosis of latent Brugada syndrome (BrS) in patients with newonset atrial fibrillation (AF) unmasked by class 1C antiarrhythmic drugs. Methods and results Between January 2000 and June 2008, all consecutive patients with new-onset AF, who after flecainide exhibited typical Brugada ECG pattern, underwent electrophysiologic, pharmacologic, and genetic testing. Among 346 patients [median age 53 years; interquartile range (IQR), 15], 11 (3.2%; median age 51 years; IQR, 19) diagnosed as lone AF exhibited typical Brugada ECG pattern. Genetic testing was negative. Ventricular tachycardia/ventricular fibrillation (VT/VF) was induced by electrophysiologic testing (five patients) or during flecainide infusion (one patient). Six patients with type 1 ECG pattern and inducible VT/VF underwent ICD implantation. During a median follow-up of 31.5 months (range: 10-85) after ICD implantation, three patients developed BrS and one of them experienced VF. Patients without ICD (five patients) remained asymptomatic during a median follow-up of 74 months. Persistent type 1 pattern occurred only in the three patients who developed BrS. Conclusion This study, for the first time, reveals the prevalence of latent BrS in patients with new-onset lone AF, which may precede VT/VF. Persistence of type 1 and ventricular tachyarrhythmias inducibility represents a marker of electrical instability leading to sudden death.

Clinical Gastroenterology and Hepatology, 2008

Background & Aims: Patients with constipation frequently complain of dyspeptic symptoms that may ... more Background & Aims: Patients with constipation frequently complain of dyspeptic symptoms that may be explained by reflex inhibition of upper-gastrointestinal motor activity by colonic stimuli. We sought to evaluate the following: (1) the prevalence of functional constipation (FC) and gastric emptying characteristics in children with functional dyspepsia (FD), and (2) the efficacy of osmotic laxatives on constipation, dyspeptic symptoms, and gastric motility. Methods: We recruited 42 children (males/females, 22/20; mean age, 80.5 mo) affected by FD (Rome II criteria). All subjects underwent ultrasonographic measurement of the total gastric emptying time (TGEt) at baseline (T0) and after 3 months (T3). Children's bowel habits and the dyspeptic symptomatic score were evaluated at entry and after 1 (T1), 2 (T2), and 3(T3) months. Constipated patients were treated with osmotic laxatives for 3 months. Dyspeptic children without constipation represented the comparison group. Results: FC was present in 28 of 42 (66.6%) patients. Constipated dyspeptic children had significantly more prolonged TGEt than subjects without constipation (median value [interquartile range], 180 (50) vs 150 (28) min, respectively; P ‫؍‬ .004). Patients on osmotic laxatives had a significant decrease in TGEt at 3 months (P < .001). The median dyspeptic symptomatic score as well as the number and consistency of evacuations per week significantly improved at T1 in comparison with T0 and even more at T2 and T3 (P < .001, for each). Conclusions: In our study group, the majority of children with FD were affected by FC associated with delayed gastric emptying. Normalization of bowel habit may improve gastric emptying as well as dyspeptic symptoms.

Circulation, 2004

Background— Radiofrequency ablation for atrial fibrillation is becoming widely practiced. Methods... more Background— Radiofrequency ablation for atrial fibrillation is becoming widely practiced. Methods and Results— Two patients undergoing circumferential pulmonary vein ablation for atrial fibrillation in different centers developed symptoms compatible with endocarditis 3 to 5 days after the procedure. Their clinical condition deteriorated rapidly, and both suffered multiple gaseous and/or septic embolic events causing cerebral and myocardial damage. One patient survived after emergency cardiac and esophageal surgery; the other died of extensive systemic embolization. An atrio-esophageal fistula was identified in both patients. Conclusions— Atrio-esophageal fistulas can occur after catheter ablation in the posterior wall of the left atrium. This diagnosis should be excluded in any patient with symptoms or signs of endocarditis after left atrial ablation, and expeditious cardiac surgery is critical if the diagnosis is confirmed. Lower power and temperature settings for applications of r...

The aim of this study was to describe the natural history of asymptomatic ventricular pre-excitat... more The 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. Background Sudden 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. Methods Between 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. Results Over 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 Ͻ 0.001), anterograde refractory period of accessory pathways (APERP) Յ240 ms (p Ͻ 0.001), and multiple accessory pathways (p Ͻ 0.001) as risk factors for potentially life-threatening arrhythmic events. Independent predictors by multivariate analysis were APERP (p ϭ 0.001) and multiple accessory pathway (p ϭ 0.001). Conclusions These 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.

European Heart Journal Supplements, 2015

The aim of this article is to understand the natural history of WPW syndrome to prevent sudden de... more The aim of this article is to understand the natural history of WPW syndrome to prevent sudden death is important to clinicians in establishing accurate prognosis and appropriate treatment. We report our experience on untreated WPW patients purely looking at the natural history of the disease. In a 15-year period (1995-2010), among 11 237 WPW patients referred to our Arrhythmology Department, a total of 1847 selected patients (820 symptomatic) underwent electrophysiological testing without ablation and were followed for a median (25th-75th) follow-up of 8 (5-8) years. During follow-up, malignant arrhythmias (MA) occurred in 16 patients (0.9%) of whom 14 (1.4%) were initially asymptomatic and two (0.2%) symptomatic (P ¼ 0.01). Potentially MA developed in 143 patients (7.7%) without difference between asymptomatic and symptomatic population (P ¼ 0.663). Benign recurrences developed in 295 patients (16%) while ventricular pre-excitation disappeared in 356 patients (19.3%) of whom 155 were initially asymptomatic. All patients were successfully ablated after arrhythmia occurrence. Patients with MA had similar accessory pathways antegrade refractory periods (AP-AERP) (P ¼ 0.064) and more frequently inducible atrioventricular reciprocating tachycardia triggering atrial fibrillation (AVRT-AF) than those with potentially MA (P , 0.001). Symptoms did not predict MA, which were predicted by AP-AERP (HR 0.912, 95% CI 0.887-0.939, P , 0.001) and AVRT-AF (HR 8.306, 95% CI 2.269-30.405, P ¼ 0.001). The natural history of WPW syndrome and the risk of sudden death essentially depend on intrinsic electrophysiological accessory pathway properties rather than on symptoms and electrophysiologic testing is the gold standard to identify patients at risk. The Authors encourage more intensive screening programs to identify asymptomatic patients at risk for prophylactic ablation.

Journal of the American College of Cardiology, Jan 17, 2018

Guidelines recommend the use of implanted cardioverter-defibrillators in patients with Brugada sy... more Guidelines recommend the use of implanted cardioverter-defibrillators in patients with Brugada syndrome and induced ventricular tachyarrhythmias, but there is no evidence supporting it. This prospective registry study was designed to explore clinical and electrophysiological predictors of malignant ventricular tachyarrhythmia inducibility in Brugada syndrome. 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). 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 induc...

Circulation. Arrhythmia and electrophysiology, 2017

There is emerging evidence that localization and elimination of abnormal electric activity in the... more There is emerging evidence that localization and elimination of abnormal electric activity in the epicardial right ventricular outflow tract may be beneficial in patients with Brugada syndrome. A total of 135 symptomatic Brugada syndrome patients having implantable cardiac defibrillator were enrolled: 63 (group 1) having documented ventricular tachycardia (VT)/ventricular fibrillation (VF) and Brugada syndrome-related symptoms, and 72 (group 2) having inducible VT/VF without ECG documentation at the time of symptoms. About 27 patients of group 1 experienced multiple implantable cardiac defibrillator shocks for recurrent VT/VF episodes. Three-dimensional maps before and after ajmaline determined the arrhythmogenic electrophysiological substrate (AES) as characterized by prolonged fragmented ventricular potentials. Primary end point was identification and elimination of AES leading to ECG pattern normalization and VT/VF noninducibility. Extensive areas of AES were found in the right v...

Circulation: Arrhythmia and Electrophysiology, 2015

Background— Whether Brugada syndrome (BrS) depends on functional epicardial substrates, which may... more Background— Whether Brugada syndrome (BrS) depends on functional epicardial substrates, which may be definitively eliminated by radiofrequency ablation, remains unknown. Methods and Results— Patients with BrS underwent epicardial mapping to identify areas of abnormal electrograms as target for radiofrequency ablation. Substrate identification consisted in mapping right ventricle epicardial surface before and after flecainide (2 mg/kg per 10 minutes). After radiofrequency ablation, flecainide and remap confirmed elimination of abnormal substrate, BrS ECG pattern, and ventricular tachycardia/ventricular fibrillation inducibility. Flecainide testing was performed at each follow-up visits ≤6 months. Fourteen patients with BrS, median age 39 years (30.3–42.3) with implantable cardioverter–defibrillator were enrolled. Low-voltage areas (<1.5 mV) were commonly identified on the anterior right free wall and right ventricular outflow tract, which increased after flecainide from 17.6 cm 2 ...

Circulation. Arrhythmia and electrophysiology, 2011

Information on comparative outcome between radiofrequency catheter ablation (RFA) and antiarrhyth... more Information on comparative outcome between radiofrequency catheter ablation (RFA) and antiarrhythmic drugs (AADs) >1 year after randomization is important for clinical decision-making. A total of 198 patients (age, 56 ± 10 years) with paroxysmal atrial fibrillation were randomly assigned to RFA (99 patients) or to AADs (99 patients). We evaluated efficacy of RFA or AADs in a comparable 48-month follow-up period according to intention-to-treat analysis. Cardiac rhythm was assessed with daily transtelephonic transmissions. Quality of life was also analyzed. At 4 years, among the 99 patients first assigned to RFA, the procedure was repeated because of recurrent atrial fibrillation/atrial tachycardia in 27 patients (27.3%). Among the 99 patients randomly assigned to AADs, 87 (87.9%) crossed over to undergo RFA and 4 years after random assignment only 12 (12.1%) were in sinus rhythm with AAD alone without ablation. Despite the high level of crossovers, at 4 years the intention-to-trea...

Therapeutic Advances in Chronic Disease, 2014

The most common extra-intestinal manifestation in patients with inflammatory bowel disease (IBD) ... more The most common extra-intestinal manifestation in patients with inflammatory bowel disease (IBD) is articular involvement, with a prevalence ranging between 17% and 39%. It is frequently characterized by an involvement of the axial joints but may also be associated with peripheral arthritis. The target of therapy in the management of arthritis associated with IBD is to reduce the inflammation and prevent any disability and/or deformity. This requires active cooperation between gastroenterologist and rheumatologist. The treatment of axial involvement has focused on the combination of exercise with nonsteroidal anti-inflammatory drugs. Immunomodulators have been efficacious in patients with peripheral arthritis and other extra-intestinal manifestations, but they are not effective for the treatment of axial symptoms of spondylitis. Tumor necrosis factor (TNF) α inhibitors have been proven to be highly effective in the treatment of IBD patients which are steroid-dependent or refractory ...

Journal of Pediatric Gastroenterology and Nutrition, 2006

Objective: To assess the effectiveness of the combined use of fecal calprotectin (FC), anti-Sacch... more Objective: To assess the effectiveness of the combined use of fecal calprotectin (FC), anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear staining antineutrophil antibody (pANCA), small intestinal permeability test (IP), and bowel wall ultrasonography measurement (BWUS) in the diagnostic work-up of children with suspected inflammatory bowel disease (IBD). Methods: All children referred for initial assessment of possible IBD were eligible. Patients with symptoms or signs (right-lower quadrant mass, perianal disease, or hematochezia) mandating a complete work-up for IBD were excluded. All enrolled patients underwent a clinical, laboratory, radiographic, and endoscopic evaluation including biopsy examinations. The immunoglobulin (Ig)G and IgA ASCA, IgG pANCA, FC, IP, and BWUS were tested in all patients at the initial assessment. Results: A final diagnosis of IBD was made in 27 patients: 17 Crohn disease and 10 ulcerative colitis. Eighteen children had other gastrointestinal diagnoses (8 functional bowel disorders, 5 food allergy-mediated diseases, 4 infectious enterocolitis, 1 familial Mediterranean fever). In patients with simultaneous abnormal values of FC, BWUS, and ASCA/pANCA, the estimated probability of having IBD was 99.47%. Patients with negative results on all tests had a 0.69% of probability of IBD. Conclusions: The incorporation of noninvasive diagnostic tests into the initial diagnostic approach may avoid unnecessary invasive procedures and facilitate clinical decision-making when the diagnosis of IBD in children is initially uncertain. JPGN 42:9-15, 2006.

The Journal of Clinical Endocrinology & Metabolism, 2007

Context: To date, the metabolic effects of the long-term metformin administration in anovulatory ... more Context: To date, the metabolic effects of the long-term metformin administration in anovulatory patients with polycystic ovary syndrome (PCOS) are known, whereas few data are available on the effects of its suspension. Objective: The objective of the study was to evaluate the effects of metformin suspension on insulin sensitivity in PCOS patients. Design: This was a prospective, randomized, placebo-controlled study. Setting: The study was conducted at the University “Magna Graecia” of Catanzaro, Italy. Patients: Patients included 30 normal-weight anovulatory PCOS women and 10 age- and body mass index-matched healthy controls. Intervention: PCOS patients were randomized to receive 1700 mg daily metformin (metformin group) or placebo tables (placebo group) for 12 months, whereas no treatment was administered in healthy women (control group). Main Outcome Measures: Clinical, endocrine, and metabolic profile and clamp insulin sensitivity index were evaluated at study entry and after 6,...

The Journal of Clinical Endocrinology & Metabolism, 2007

Context: Polycystic ovary syndrome (PCOS) is an endocrine disease closely related to several risk... more Context: Polycystic ovary syndrome (PCOS) is an endocrine disease closely related to several risk factors for cardiovascular disease. An impaired cardiopulmonary functional capacity was previously demonstrated in PCOS women. No data regarding the effects of a structured exercise training (ET) program on cardiopulmonary functional capacity in PCOS women are available. Objective: Our objective was to evaluate the effects of a 3-month ET program on cardiopulmonary functional capacity in young PCOS women.

The Journal of Clinical Endocrinology & Metabolism, 2006

Context: Polycystic ovary syndrome (PCOS) is associated with early impairment of vascular structu... more Context: Polycystic ovary syndrome (PCOS) is associated with early impairment of vascular structure and a low-grade chronic inflammation. Aldosterone is a well-recognized cardiovascular risk (CVR) factor and is related to inflammatory processes. Objective: Our objective was to investigate serum aldosterone levels in PCOS and correlate them to some CVR factors and early atherosclerotic markers. Design and Setting: A prospective baseline-controlled clinical study was conducted at the University “Federico II” of Naples School of Medicine (Naples, Italy). Patients: Fifty PCOS women age- and body mass index-matched with 50 healthy women were enrolled. Mean Outcome Measures: Anthropometric, hormonal, and metabolic patterns, including plasma aldosterone, renin, and C-reactive protein, were measured in each subject. Intima-media thickness was also evaluated in each patient and control. Results: Aldosterone levels were significantly increased (P < 0.001) in PCOS compared with healthy wome...

The Journal of Clinical Endocrinology & Metabolism, 2005

Context: Although metformin has been shown to be effective in the treatment of anovulation in wom... more Context: Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients. Objective: The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS. Design: We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial. Setting: The study was conducted at the University “Magna Graecia” of Catanzaro, Catanzaro, Italy. Patients: One hundred nonobese primary infertile anovulatory women with PCOS participated. Interventions: We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each. Mean outcome measures: The main outcome measures were ovulation, pregnan...

The Journal of Clinical Endocrinology & Metabolism, 2005

Context: Recent data indicate that women affected by the polycystic ovary syndrome (PCOS) are at ... more Context: Recent data indicate that women affected by the polycystic ovary syndrome (PCOS) are at greater risk for cardiovascular disease and that metformin may improve the metabolic alterations in these patients.

The Journal of Clinical Endocrinology & Metabolism, 2006

Context: Insulin resistance is a feature of polycystic ovary syndrome (PCOS), and it is related t... more Context: Insulin resistance is a feature of polycystic ovary syndrome (PCOS), and it is related to mitochondrial function, particularly with maximal oxygen consumption (VO 2max). At the moment, no evaluation of cardiopulmonary functional capacity in young patients with PCOS has been performed.

Human Reproduction, 2005

BACKGROUND: There are few data in the literature regarding the utility of metfomin before and dur... more BACKGROUND: There are few data in the literature regarding the utility of metfomin before and during gonadotrophin administration in women with polycystic ovary syndrome (PCOS). The aim of the present study was to assess the effect of the pre-treatment and co-administration of metformin in infertile PCOS women treated with controlled ovarian stimulation (COS) followed by timed intercourse (TI) or intrauterine insemination (IUI). METHODS: Seventy insulin-resistant primary infertile women with PCOS were randomized to receive metformin cloridrate (850 mg twice daily; group A) or placebo tablets (two tablets daily; group B) for 3 months. Three trials of COS using highly purified urinary FSH (hpFSH) plus TI/IUI were performed. Number of ampoules of gonadotrophin used, duration of the ovarian stimulation, cycle cancellation, ovulation, pregnancy, abortion, live birth, mono-ovulatory cycles, multiple pregnancies and ovarian hyperstimulation syndrome (OHSS) rates were assessed. RESULTS: No difference between groups was detected in ovulation, cycle cancellation, pregnancy, abortion, live birth, multiple pregnancies and OHSS rates. The mono-ovulatory cycle rates were significantly (P = 0.002) more frequent in group A than in group B, whereas the days of stimulation for non-cancelled cycles and the number of vials of gonadotrophins used were significantly (P < 0.001) higher in group A than in group B. CONCLUSION: In insulin-resistant women with PCOS, metformin pre-treatment and co-administration with hpFSH increases the mono-ovulatory cycles.

Human Reproduction, 2005

BACKGROUND: In Italy, a recent law has imposed a ban on the fertilization of more than three oocy... more BACKGROUND: In Italy, a recent law has imposed a ban on the fertilization of more than three oocytes at one time, and all resulting embryos produced must be transferred simultaneously. The aim of the present controlled study was to assess the clinical feasibility and efficacy of the perifollicular vascularity assessment for oocyte selection in IVF cycles. METHODS: Fifty-four young primary infertile non-obese women (27 cases and 27 age-and BMI-matched controls) underwent IVF cycles. The choice of the oocytes to fertilize was performed according to perifollicular vascularization in the experimental group, whereas in the control group, the standard morphologic criteria alone were used. The dose of gonadotrophins used, the dominant follicles obtained, the duration of the ovarian stimulation, the number of oocytes retrieved, the number/quality of oocytes fertilized and of cleaved embryos, cycle cancellation, implantation, clinical pregnancy, ongoing pregnancy, multiple pregnancies and ovarian hyperstimulation syndrome rates were assessed in each group. RESULTS: The assessment of perifollicular vascularity was feasible in 88.9% of cases. No difference between groups was detected in any parameter evaluated. CONCLUSION: Power Doppler assessment of perifollicular vascularity seems to have no clinical utility for oocyte selection in IVF cycles for young infertile women.

Human Reproduction, 2005

BACKGROUND: Metformin has been shown to improve fertility in anovulatory patients with polycystic... more BACKGROUND: Metformin has been shown to improve fertility in anovulatory patients with polycystic ovary syndrome (PCOS), inducing not only a high ovulation and pregnancy rate but also reducing the incidence of miscarriages. The aim of the present study was to evaluate the uterine effects of metformin in patients with PCOS who ovulated under metformin. METHODS: Thirty-seven non-obese primary infertile anovulatory patients with PCOS and another 30 age-and body mass index-matched healthy women (control group) were studied. PCOS patients were treated with metformin (850 mg twice daily) for 6 months, whereas the control group did not receive any treatment. In these PCOS patients who ovulated whilst under metformin treatment (PCOS group) and in controls, uterine, sub-endometrial and endometrial blood flow, and endometrial thickness and pattern were evaluated using serial ultrasonographic assessments. RESULTS: Before treatment, uterine, sub-endometrial and endometrial blood flows were significantly lower in patients with PCOS than in the control group. All indexes of uterine vascularization were significantly improved in the PCOS group with metformin treatment and were not different from the controls. Nor was any difference in endometrial thickness and pattern detected between PCOS and control groups. After grouping the data of PCOS patients who ovulated under metformin for cycles with favourable/unfavourable reproductive outcome, no difference in any parameter was observed. CONCLUSIONS: Metformin improves all surrogate markers of endometrial receptivity in PCOS patients, without difference between patients who had favourable or unfavourable reproductive outcome.

European Heart Journal, 2009

To evaluate the prevalence, clinical significance, and prognosis of latent Brugada syndrome (BrS)... more To evaluate the prevalence, clinical significance, and prognosis of latent Brugada syndrome (BrS) in patients with newonset atrial fibrillation (AF) unmasked by class 1C antiarrhythmic drugs. Methods and results Between January 2000 and June 2008, all consecutive patients with new-onset AF, who after flecainide exhibited typical Brugada ECG pattern, underwent electrophysiologic, pharmacologic, and genetic testing. Among 346 patients [median age 53 years; interquartile range (IQR), 15], 11 (3.2%; median age 51 years; IQR, 19) diagnosed as lone AF exhibited typical Brugada ECG pattern. Genetic testing was negative. Ventricular tachycardia/ventricular fibrillation (VT/VF) was induced by electrophysiologic testing (five patients) or during flecainide infusion (one patient). Six patients with type 1 ECG pattern and inducible VT/VF underwent ICD implantation. During a median follow-up of 31.5 months (range: 10-85) after ICD implantation, three patients developed BrS and one of them experienced VF. Patients without ICD (five patients) remained asymptomatic during a median follow-up of 74 months. Persistent type 1 pattern occurred only in the three patients who developed BrS. Conclusion This study, for the first time, reveals the prevalence of latent BrS in patients with new-onset lone AF, which may precede VT/VF. Persistence of type 1 and ventricular tachyarrhythmias inducibility represents a marker of electrical instability leading to sudden death.

Clinical Gastroenterology and Hepatology, 2008

Background & Aims: Patients with constipation frequently complain of dyspeptic symptoms that may ... more Background & Aims: Patients with constipation frequently complain of dyspeptic symptoms that may be explained by reflex inhibition of upper-gastrointestinal motor activity by colonic stimuli. We sought to evaluate the following: (1) the prevalence of functional constipation (FC) and gastric emptying characteristics in children with functional dyspepsia (FD), and (2) the efficacy of osmotic laxatives on constipation, dyspeptic symptoms, and gastric motility. Methods: We recruited 42 children (males/females, 22/20; mean age, 80.5 mo) affected by FD (Rome II criteria). All subjects underwent ultrasonographic measurement of the total gastric emptying time (TGEt) at baseline (T0) and after 3 months (T3). Children's bowel habits and the dyspeptic symptomatic score were evaluated at entry and after 1 (T1), 2 (T2), and 3(T3) months. Constipated patients were treated with osmotic laxatives for 3 months. Dyspeptic children without constipation represented the comparison group. Results: FC was present in 28 of 42 (66.6%) patients. Constipated dyspeptic children had significantly more prolonged TGEt than subjects without constipation (median value [interquartile range], 180 (50) vs 150 (28) min, respectively; P ‫؍‬ .004). Patients on osmotic laxatives had a significant decrease in TGEt at 3 months (P < .001). The median dyspeptic symptomatic score as well as the number and consistency of evacuations per week significantly improved at T1 in comparison with T0 and even more at T2 and T3 (P < .001, for each). Conclusions: In our study group, the majority of children with FD were affected by FC associated with delayed gastric emptying. Normalization of bowel habit may improve gastric emptying as well as dyspeptic symptoms.

Circulation, 2004

Background— Radiofrequency ablation for atrial fibrillation is becoming widely practiced. Methods... more Background— Radiofrequency ablation for atrial fibrillation is becoming widely practiced. Methods and Results— Two patients undergoing circumferential pulmonary vein ablation for atrial fibrillation in different centers developed symptoms compatible with endocarditis 3 to 5 days after the procedure. Their clinical condition deteriorated rapidly, and both suffered multiple gaseous and/or septic embolic events causing cerebral and myocardial damage. One patient survived after emergency cardiac and esophageal surgery; the other died of extensive systemic embolization. An atrio-esophageal fistula was identified in both patients. Conclusions— Atrio-esophageal fistulas can occur after catheter ablation in the posterior wall of the left atrium. This diagnosis should be excluded in any patient with symptoms or signs of endocarditis after left atrial ablation, and expeditious cardiac surgery is critical if the diagnosis is confirmed. Lower power and temperature settings for applications of r...

The aim of this study was to describe the natural history of asymptomatic ventricular pre-excitat... more The 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. Background Sudden 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. Methods Between 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. Results Over 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 Ͻ 0.001), anterograde refractory period of accessory pathways (APERP) Յ240 ms (p Ͻ 0.001), and multiple accessory pathways (p Ͻ 0.001) as risk factors for potentially life-threatening arrhythmic events. Independent predictors by multivariate analysis were APERP (p ϭ 0.001) and multiple accessory pathway (p ϭ 0.001). Conclusions These 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.

European Heart Journal Supplements, 2015

The aim of this article is to understand the natural history of WPW syndrome to prevent sudden de... more The aim of this article is to understand the natural history of WPW syndrome to prevent sudden death is important to clinicians in establishing accurate prognosis and appropriate treatment. We report our experience on untreated WPW patients purely looking at the natural history of the disease. In a 15-year period (1995-2010), among 11 237 WPW patients referred to our Arrhythmology Department, a total of 1847 selected patients (820 symptomatic) underwent electrophysiological testing without ablation and were followed for a median (25th-75th) follow-up of 8 (5-8) years. During follow-up, malignant arrhythmias (MA) occurred in 16 patients (0.9%) of whom 14 (1.4%) were initially asymptomatic and two (0.2%) symptomatic (P ¼ 0.01). Potentially MA developed in 143 patients (7.7%) without difference between asymptomatic and symptomatic population (P ¼ 0.663). Benign recurrences developed in 295 patients (16%) while ventricular pre-excitation disappeared in 356 patients (19.3%) of whom 155 were initially asymptomatic. All patients were successfully ablated after arrhythmia occurrence. Patients with MA had similar accessory pathways antegrade refractory periods (AP-AERP) (P ¼ 0.064) and more frequently inducible atrioventricular reciprocating tachycardia triggering atrial fibrillation (AVRT-AF) than those with potentially MA (P , 0.001). Symptoms did not predict MA, which were predicted by AP-AERP (HR 0.912, 95% CI 0.887-0.939, P , 0.001) and AVRT-AF (HR 8.306, 95% CI 2.269-30.405, P ¼ 0.001). The natural history of WPW syndrome and the risk of sudden death essentially depend on intrinsic electrophysiological accessory pathway properties rather than on symptoms and electrophysiologic testing is the gold standard to identify patients at risk. The Authors encourage more intensive screening programs to identify asymptomatic patients at risk for prophylactic ablation.