Giuseppe Pacileo

AORN Ospedali dei Colli, Napoli, Campania, Italy

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Publications (208)530.24 Total impact

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    ABSTRACT: Background: In hypertrophic cardiomyopathy (HCM), most of the factors associated with the risk of sudden cardiac death (SCD) are also involved in the pathophysiology of exercise limitation. The present multicentre study investigated possible ability of cardiopulmonary exercise test in improving contemporary strategies for SCD risk stratification. Methods: A total of 623 consecutive outpatients with HCM, from five tertiary Italian HCM centres, were recruited and prospectively followed, between September 2007 and April 2015. The study composite end point was SCD, aborted SCD and appropriate implantable cardioverter defibrillator (ICD) interventions. Results: During a median follow-up of 3.7 years (25th-75th centile: 2.2-5.1 years), 25 patients reached the end point at 5 years (3 SCD, 4 aborted SCD, 18 appropriate ICD interventions). At multivariate analysis, ventilation versus carbon dioxide relation during exercise (VE/VCO2 slope) remains independently associated to the study end point either when challenged with the 2011 American College of Cardiology Foundation/American Heart Association guidelines-derived score (C index 0.748) or with the 2014 European Society of Cardiology guidelines-derived score (C index 0.750). A VE/VCO2 slope cut-off value of 31 showed the best accuracy in predicting the SCD end point within the entire HCM study cohort (sensitivity 64%, specificity 72%, area under the curve 0.72). Conclusions: Our data suggest that the VE/VCO2 slope might improve SCD risk stratification, particularly in those HCM categories classified at low-intermediate SCD risk according to contemporary guidelines. There is a need for further larger studies, possibly on independent cohorts, to confirm our preliminary findings.
    No preview · Article · Feb 2016 · Heart (British Cardiac Society)
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    ABSTRACT: Aims: Prevalence and clinical significance of right atrial enlargement (RAE) has been poorly characterized in hypertrophic cardiomyopathy. Methods: One hundred and sixty consecutive patients with hypertrophic cardiomyopathy (35.5 ± 20 years; 64% men) were studied. They underwent clinical examination, standard ECG, M-mode, 2D and Doppler echocardiography, stress test and ECG Holter monitoring. Major adverse cardiac events were considered: cardiac death (sudden death, heart failure death); cardiac transplant; resuscitated cardiac arrest or appropriate implantable cardioverter defibrillator discharge. Genetic analysis of eight sarcomeric genes was performed using Sanger sequencing. Results: RAE was observed in 22 patients (14%), associated with left atrial enlargement in all cases. Patients with RAE were likely to have restrictive mitral pattern (P < 0.001) and had higher New York Heart Association (P < 0.001), N-terminal prohormone of brain natriuretic peptide (P < 0.001), left atrial volume index (P < 0.001), lateral (P = 0.04) and septal (P = 0.002) E/e', systolic pulmonary artery pressure (P < 0.001) and lower ejection fraction (all P < 0.001). On cardiopulmonary exercise testing, peak VO2 was lower and VE/VCO2 higher in patients with RAE (P < 0.001). During a mean follow-up of 4 ± 2.1 years, 30 major adverse cardiac events in 24 patients (15%) were observed. Cox proportional hazards regression analysis identified RAE as an independent predictor of major adverse cardiac events (odds ratio = 2.6; confidence interval 1.5-4.6; P = 0.001). In patients with RAE who were genetically tested, there was a higher prevalence of sarcomeric gene mutations (68%), double mutations (16%) and troponin T mutations (21%). Conclusion: RAE is present in a small subset of patients with hypertrophic cardiomyopathy, and largely reflects increased pulmonary pressures because of severe diastolic and/or systolic left ventricular dysfunction. Patients with RAE had a higher prevalence of sarcomeric gene mutations, troponin T mutations and complex genotypes. In conclusion, RAE may serve as a very useful marker of disease progression and adverse outcome in patients with sarcomeric hypertrophic cardiomyopathy.
    No preview · Article · Jan 2016 · Journal of Cardiovascular Medicine

  • No preview · Article · Oct 2015 · International journal of cardiology
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    ABSTRACT: Late arterial hypertension has been identified as a major predictor for morbidity and mortality in aortic coarctation (AoC) patients. Few data are available about efficacy and tolerability of angiotensin converting enzyme inhibitors vs beta-blockers in young AoC patients. This study aimed to evaluate the tolerability and efficacy on 24-h blood pressure (BP) and left ventricular mass/height(2.7) (LVMI), of atenolol vs enalapril. We enrolled consecutive AoC hypertensive patients with (a) no history of BP treatment or after >48 h of withdrawn, (b) aged 6-20 years, (c) body mass index (BMI) <90th percentile for age and sex, (d) >12 months from a successful AoC repair and (e) no major associated cardiovascular abnormalities. All patient were evaluated with 24-h ambulatory BP monitoring, standard echocardiography, strain-strain rate imaging, at enrolment, 3, 6 and 12 months of treatment. We studied 51 AoC patients (13±3.9 years, BMI: 21.4±4.3 kg m(-2)). Patients were randomly assigned at atenolol treatment (n=26), or enalapril treatment (n=25). The mean follow-up duration was 11±2 months. Both drugs were able to significantly reduce 24-systolic BP (SBP; atenolol: 133±11 mm Hg vs 124±16 mm Hg, P=0.016; enalapril: 135±6 mm Hg vs 127±7 mm Hg, P=0.001). Only enalapril was able to significantly reduce LVMI (47±12 vs 39.6±10 g m(-)(2.7), P=0.016). Only in atenolol group in two cases (7.7%) drug withdrawal was needed because of adverse events. Enalapril and atenolol are similarly effective in reducing SBP. However, only enalapril demonstrated a significant reduction of LVMI. In no case, enalapril was stopped because of adverse events.Journal of Human Hypertension advance online publication, 20 August 2015; doi:10.1038/jhh.2015.87.
    No preview · Article · Aug 2015 · Journal of human hypertension
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    ABSTRACT: Atrial fibrillation (AF) is common in heart failure (HF). It is unclear whether AF has an independent prognostic role in HF. The aim of the present study was to assess the prognostic role of AF in HF patients with reduced ejection fraction (EF). HF patients were followed in 17 centers for 3.15years (1.51-5.24). Study endpoints were the composite of cardiovascular (CV) death and heart transplant (HTX) and all-cause death. Data analysis was performed considering the entire population and a 1 to 1 match between sinus rhythm (SR) and AF patients. Match process was done for age±5, gender, left ventricle EF±5, peakVO2±3 (ml/min/kg) and recruiting center. A total of 3447 patients (SR=2882, AF=565) were included in the study. Considering the entire population, CV death and HTX occurred in 114 (20%) AF vs. 471 (16%) SR (p=0.026) and all-cause death in 130 (23%) AF vs. 554 (19.2%) SR patients (p=0.039). At univariable Cox analysis, AF was significantly related to prognosis. Applying a multivariable model based on all variables significant at univariable analysis (EF, peakVO2, ventilation/carbon dioxide relationship slope, sodium, kidney function, hemoglobin, beta-blockers and digoxin) AF was no longer associated with adverse outcomes. Matching procedure resulted in 338 couples. CV death and HTX occurred in 63 (18.6%) AF vs. 74 (21.9%) SR (p=0.293) and all-cause death in 71 (21%) AF vs. 80 (23.6%) SR (p=0.406), with no survival differences between groups. In systolic HF AF is a marker of disease severity but not an independent prognostic indicator. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
    Full-text · Article · May 2015 · European Journal of Internal Medicine
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    ABSTRACT: Chronic kidney disease is associated with sympathetic activation and muscle abnormalities, which may contribute to decreased exercise capacity. We investigated the correlation of renal function with peak exercise oxygen consumption (V̇O2) in heart failure (HF) patients.Methods and Results:We recruited 2,938 systolic HF patients who underwent clinical, laboratory, echocardiographic and cardiopulmonary exercise testing. The patients were stratified according to estimated glomerular filtration rate (eGFR). Mean follow-up was 3.7 years. The primary outcome was a composite of cardiovascular death and urgent heart transplantation at 3 years. On multivariable regression, eGFR was predictor of peakV̇O2(P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, B-type natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakV̇O2<12 ml·kg(-1)·min(-1)was 1.75 (95% confidence interval (CI): 1.06-2.91; P=0.0292) in patients with eGFR ≥60, 1.77 (0.87-3.61; P=0.1141) in those with eGFR of 45-59, and 2.72 (1.01-7.37; P=0.0489) in those with eGFR <45 ml·min(-1)·1.73 m(-2). The area under the receiver-operating characteristic curve for peakV̇O2<12 ml·kg(-1)·min(-1)was 0.63 (95% CI: 0.54-0.71), 0.67 (0.56-0.78), and 0.57 (0.47-0.69), respectively. Testing for interaction was not significant. Renal dysfunction is correlated with peakV̇O2. A peakV̇O2cutoff of 12 ml·kg(-1)·min(-1)offers limited prognostic information in HF patients with more severely impaired renal function. (Circ J 2015; 79: 583-591).
    Full-text · Article · Feb 2015 · Circulation Journal
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    ABSTRACT: ABSTRACT Mitral regurgitation (MR) is the second most common heart valve disease worldwide. Currently, the management of MR is based on medical therapy (including biventricular pacing), surgery (mitral valve replacement or repair) and percutaneous therapy. However, in spite of guideline recommendations, 50% of individuals assessed in the Euro Heart Survey were not referred to surgical intervention due to comorbidities or real or perceived high risks for cardiac surgery; thus, in recent years, the focus of research has shifted to the development of percutaneous approaches to treat severe MR in order to restore valve function in a minimally invasive fashion. Among these techniques, the percutaneous mitral valve repair procedure using the MitraClip(®) system (Abbott Vascular, IL, USA) is one of the most promising. Usually, patient selection for MitraClip implantation is based on careful echocardiographic assessment of valve disease; however, although definitive data are lacking, evidence is mounting for a multiparametric approach including the evaluation of the functional status of patients.
    No preview · Article · Nov 2014 · Future Cardiology
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    ABSTRACT: Background: Oxygen uptake at the anaerobic threshold (VO2AT), a submaximal exercise-derived variable, independent of patients' motivation, is a marker of outcome in heart failure (HF). However, previous evidence of VO2AT values paradoxically higher in HF patients with permanent atrial fibrillation (AF) than in those with sinus rhythm (SR) raised uncertainties. Design: We tested the prognostic role of VO2AT in a large cohort of systolic HF patients, focusing on possible differences between SR and AF. Methods: Altogether 2976 HF patients (2578 with SR and 398 with AF) were prospectively followed. Besides a clinical examination, each patient underwent a maximal cardiopulmonary exercise test (CPET). Results: The follow-up was analysed for up to 1500 days. Cardiovascular death or urgent cardiac transplantation occurred in 303 patients (250 (9.6%) patients with SR and 53 (13.3%) patients with AF, p=0.023). In the entire population, multivariate analysis including peak oxygen uptake (VO2) showed a prognostic capacity (C-index) similar to that obtained including VO2AT (0.76 vs 0.72). Also, left ventricular ejection fraction, ventilation vs carbon dioxide production slope, β-blocker and digoxin therapy proved to be significant prognostic indexes. The receiver-operating characteristic (ROC) curves analysis showed that the best predictive VO2AT cut-off for the SR group was 11.7 ml/kg/min, while it was 12.8 ml/kg/min for the AF group. Conclusions: VO2AT, a submaximal CPET-derived parameter, is reliable for long-term cardiovascular mortality prognostication in stable systolic HF. However, different VO2AT cut-off values between SR and AF HF patients should be adopted.
    No preview · Article · Sep 2014 · European Journal of Preventive Cardiology
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    ABSTRACT: The physiological importance of the right ventricle (RV) has been underestimated over the past years. Finally in the early 1950s through the 1970s, cardiac surgeons recognized the importance of RV function. Since then, the importance of RV function has been recognized in many acquired cardiac heart disease. RV can be mainly or together with left ventricle (LV) affected by inherited or acquired cardiomyopathy. In fact, RV morphological and functional remodeling occurs more common during cardiomyopathies than in ischemic cardiomyopathies and more closely parallels LV dysfunction.Moreover, there are some cardiomyopathy subtypes showing a predominant or exclusive involvement of the RV, and they are probably less known by cardiologists. The clinical approach to right ventricular cardiomyopathies is often challenging. Imaging is the first step to raise the suspicion and to guide the diagnostic process. In the differential diagnosis, cardiologists should consider athlete's heart, congenital heart diseases, multisystemic disorders, and inherited arrhythmias. However, a multiparametric and multidisciplinary approach, involving cardiologists, experts in imaging, geneticists, and pathologists with a specific expertise in these heart muscle disorders is required.
    No preview · Article · Sep 2014 · Echocardiography
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    Rita Gravino · Giuseppe Pacileo

    Preview · Article · Jul 2014
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    ABSTRACT: Diagnosis within RASopathies still represents a challenge. Nevertheless, many efforts have been made by clinicians to identify specific clinical features which might help in differentiating one disorder from another. Here, we describe a child initially diagnosed with Neurofibromatosis-Noonan syndrome. The follow-up of the proband, the clinical evaluation of his father together with a gene-by-gene testing approach led us to the proper diagnosis. We report a 8-year-old male with multiple cafe-au-lait macules, several lentigines and dysmorphic features that suggest Noonan syndrome initially diagnosed with Neurofibromatosis-Noonan syndrome. However, after a few years of clinical and ophthalmological follow-up, the absence of typical features of Neurofibromatosis type 1 and the lack of NF1 mutation led us to reconsider the original diagnosis. A new examination of the patient and his similarly affected father, who was initially referred as healthy, led us to suspect LEOPARD syndrome, The diagnosis was then confirmed by the occurrence in both patients of a heterozygous mutation c.1403 C > T, p.(Thr468Met), of PTPN11. Subsequently, the proband was also found to have type-1 Arnold-Chiari malformation in association with syringomyelia. Our experience suggests that differential clinical diagnosis among RASopathies remains ambiguous and raises doubts on the current diagnostic clinical criteria. In some cases, genetic tests represent the only conclusive proof for a correct diagnosis and, consequently, for establishing individual prognosis and providing adequate follow-up. Thus, molecular testing represents an essential tool in differential diagnosis of RASophaties. This view is further strengthened by the increasing accessibility of new sequencing techniques.Finally, to our knowledge, the described case represents the third report of the occurrence of Arnold Chiari malformation and the second description of syringomyelia with LEOPARD syndrome.
    Full-text · Article · Apr 2014 · BMC Medical Genetics
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    ABSTRACT: Infection with HIV may lead to the development of cardiomyopathy as improved antiretroviral regimens continue to prolong patient life. However, advanced therapeutic options, such as heart transplant, have until recently been precluded to HIV-positive persons. A favorable long-term outcome has been obtained after kidney or liver transplant in HIV-positive recipients fulfilling strict virological and clinical criteria. We recently reported the first heart transplant in a HIV-infected patient carried out in our center. In this article, we detail the major challenges we faced with the management of antiretroviral and immunosuppressive treatments over the first 3 years post-transplant. The patient had developed dilated cardiomyopathy while on antiretroviral treatment with zidovudine, lamivudine and efavirenz. He was in WHO Stage 1 of HIV infection and had normal CD4+ count and persistently undetectable HIV-RNA. In spite of cardiac resynchronization therapy and maximal drug therapy, the patient progressed to end stage heart failure, requiring heart transplant. He was placed on a standard immune suppressive protocol including cyclosporine A and everolimus. Despite its potential pharmacokinetic interaction with efavirenz, everolimus was chosen to reduce the long-term risk of opportunistic neoplasia. Plasma levels of both drugs were monitored and remained within the target range, although high doses of everolimus were needed. There were no infectious, neoplastic or metabolic complications during a 3-year follow-up. In summary, our experience supports previous data showing that cardiac transplantation should not be denied to carefully selected HIV patients. Careful management of drug interactions and adverse events is mandatory.
    No preview · Article · Mar 2014 · International journal of immunopathology and pharmacology
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    ABSTRACT: Hypertrophic cardiomyopathy is a relatively frequent disease with a prevalence of 0.2% worldwide and a remarkable genetic heterogeneity, with more than 30 causative genes reported to date. Current PCR-based strategies are inadequate for genomic investigations involving many candidate genes. Here, we report a next-generation sequencing procedure associated with DNA sequence capture that is able to sequence 202 cardiomyopathy-related genes simultaneously. We developed a complementary data analysis pipeline to select and prioritize genetic variants. The overall procedure can screen a large number of target genes simultaneously, thereby potentially revealing new disease-causing and modifier genes. By using this procedure, we analyzed hypertrophic cardiomyopathy patients in a shorter time and at a lower cost than with current procedures. The specificity of the next-generation sequencing-based procedure is at least as good as other techniques routinely used for mutation searching, and the sensitivity is much better. Analysis of the results showed some novel variants potentially involved in the pathogenesis of hypertrophic cardiomyopathy: a missense mutation in MYH7 and a nonsense variant in INS-IGF2 (patient 1), a splicing variant in MYBPC3 and an indel/frameshift variant in KCNQ1 (patient 2), and two concomitant variations in CACNA1C (patient 3). Sequencing of DNA from the three patients within a pool allowed detection of most variants identified in each individual patient, indicating that this approach is a feasible and cost-effective procedure.
    Full-text · Article · Oct 2013 · The Journal of molecular diagnostics: JMD
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    Full-text · Article · Jul 2013 · International journal of cardiology
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    ABSTRACT: Natriuretic peptides (NPs) counter the effects of volume overload or adrenergic activation of the cardiovascular system. They are able to induce arterial vasodilatations, natriuresis and diuresis, and they reduce the activities of the renin-angiotensin-aldosterone system and the sympathetic nervous system. However, in addition to wall stress, other factors have been associated with elevated natriuretic peptide levels. Since 2000, because of their characteristics, NPs have become quantitative plasma biomarkers of heart failure. Nowadays, NPs play an important role not only in the diagnosis of heart failure, but also for a prognostic purpose and a guide to medical therapy. Finally, a new drug that modulates the NP system or recombinant analogs of NPs are now available in patients with heart failure.
    Full-text · Article · Jul 2013 · Future Cardiology
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    ABSTRACT: Cardiomyopathies are a heterogeneous group of diseases of the myocardium that represent a major cause of morbidity and mortality due to progressive heart failure or sudden death. Cardiac resynchronization therapy has become an essential therapeutic tool in the treatment of heart failure patients today. It is an optimal choice in patients with dilated cardiomyopathy; however, its role in the management of patients with other forms of cardiomyopathies is still under investigation. This article discusses the most recent evidence for the use of cardiac resynchronization therapy in cardiomyopathies.
    Full-text · Article · Jun 2013 · Journal of Cardiovascular Medicine
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    ABSTRACT: We report an Italian family in which the proband showed a severe phenotype characterized by the association of congenital fiber type disproportion (CFTD) with a left ventricular non-compaction cardiomyopathy (LVNC). This study was focused on the identification of the responsible gene/s.Methods and results: Using the whole-exome sequencing approach, we identified the proband homozygous missense mutations in two genes, the myosin heavy chain 7B (MYH7B) and the integrin alpha 7 (ITGA7). Both genes are expressed in heart and muscle tissues, and both mutations were predicted to be deleterious and were not found in the healthy population.The R890C mutation in the MYH7B gene segregated with the LVNC phenotype in the examined family. It was also found in one unrelated patient affected by LVNC, confirming a causative role in cardiomyopathy.The E882K mutation in the ITGA7 gene, a key component of the basal lamina of muscle fibers, was found only in the proband, suggesting a role in CFTD. This study identifies two novel disease genes. Mutation in MYH7B causes a classical LVNC phenotype, whereas mutation in ITGA7 causes CFTD. Both phenotypes represent alterations of skeletal and cardiac muscle maturation and are usually not severe. The severe phenotype of the proband is most likely due to a synergic effect of these two mutations.This study provides new insights into the genetics underlying Mendelian traits and demonstrates a role for digenic inheritance in complex phenotypes.
    Full-text · Article · Jun 2013 · Orphanet Journal of Rare Diseases
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    ABSTRACT: Percutaneous closure currently is widely considered to be the first-choice therapeutic option in the treatment of ostium secundum atrial septal defect (ASD). The Amplatzer Septal Occluder (ASO) device is the most used prosthesis, although its influence on cardiac function still is under active investigation. This study aimed to evaluate the impact of the ASO device size on left ventricular (LV) function in pediatric patients using the speckle-tracking strain imaging technology. The study enrolled 43 nonobese pediatric patients submitted to percutaneous ASD closure with the Amplatzer Septal Occluder device and grouped them according to the size of the occluding prosthesis into three groups: a small-device group (≤10 mm, group 1), a medium-size-device group (11-16 mm, group 2), and a large-device group (≥17 mm, group 3). Echocardiographic data were compared among the groups and with the data of an age-, weight-, and gender-matched control group (50 patients). The large-device group showed a significant impairment in the strain rate value of the basal LV segments. In particular, the mean basal circumferential and radial strain rate values were lower than either normal or the values of the small- and medium-device groups. However, only the absolute device diameter reached statistical significance in the multivariate analysis. The large Amplatzer Septal Occluding device significantly impaired LV systolic function, particularly that of juxtaprosthetic segments, as shown in the strain rate analysis.
    No preview · Article · Apr 2013 · Pediatric Cardiology
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    ABSTRACT: Takotsubo cardiomyopathy (TTC) is an enigmatic disease with a multifactorial and still unresolved pathogenesis. Recent experimental and clinical observation has suggested a role for genetics in the pathogenesis of TTC. Ethnic as well as seasonal variation in the prevalence of TTC is well described, but it is only recently that familial cases of TTC have been reported. In recent years technological advances in exome capture and DNA sequencing have offered clinicians a new opportunity to discover genetics-related disease. This article explores the role of genetic mechanisms that might explain or modulate the pathogenesis of TTC.
    Full-text · Article · Apr 2013 · Heart Failure Clinics
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    ABSTRACT: OBJECTIVES: To determine ICD efficacy in children/adolescents with HCM. BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden death (SD) in the young. Availability of the implantable cardioverter-defibrillator (ICD) over the last decade for HCM has demonstrated the potential for SD prevention, predominantly in adult patients. METHODS: A multicenter international registry of ICDs implanted (1987 to 2011) in 224 unrelated children and adolescents with HCM judged at high risk for SD was assembled. Patients received ICDs for primary (n = 188) or secondary (n = 36) prevention after undergoing evaluation at 22 referral and non-referral institutions in U.S., Europe and Australia. RESULTS: Defibrillators activated appropriately to terminate ventricular tachycardia/fibrillation (VT/VF) in 43 of 224 patients (19%) over a 4.3 ± 3.3 years period. ICD intervention rates were 4.5%/year overall, 14.0%/year for secondary prevention after cardiac arrest, and 3.1%/year for primary prevention based on risk factors (5-year cumulative probability; 17%). Implant to first appropriate discharge was 2.9 ± 2.7 years (range to 8.6 years). Primary prevention discharge rate terminating VT/VF was the same in patients implanted for 1, 2, or ≥ 3 risk factors (12/88, 14%; 10/71, 14%; 4/29, 14%; respectively; p = 1.00). Extreme LV hypertrophy was the most common risk factor present (alone or in combination with other markers) in patients experiencing primary prevention interventions (17/26; 65%). ICD-related complications, particularly inappropriate shocks and lead malfunction, occurred in 91 patients (41%), at 17 ± 5 years. CONCLUSIONS: In a high-risk pediatric HCM cohort, ICD interventions terminating life-threatening ventricular tachyarrhythmias were frequent. Extreme LV hypertrophy was most frequently associated with appropriate interventions. The rate of device complications adds a measure of complexity to ICD decisions in this age group.
    Full-text · Article · Mar 2013 · Journal of the American College of Cardiology

Publication Stats

2k Citations
530.24 Total Impact Points

Institutions

  • 2011-2015
    • AORN Ospedali dei Colli
      Napoli, Campania, Italy
  • 1998-2015
    • Second University of Naples
      • Faculty of Medicine and Surgery
      Caserta, Campania, Italy
  • 1994-2015
    • Monaldi Hospital
      Napoli, Campania, Italy
  • 2014
    • Università degli studi di Foggia
      Foggia, Apulia, Italy
  • 2009-2011
    • Naples Eastern University
      Napoli, Campania, Italy
  • 1999-2011
    • University of Naples Federico II
      • Department of Molecular Medicine and Medical Biotechnology
      Napoli, Campania, Italy