Giuseppe Pacileo

AORN Ospedali dei Colli, Cicciano, Campania, Italy

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Publications (186)456.52 Total impact

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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.
    Echocardiography 09/2014; · 1.26 Impact Factor
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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.
    BMC Medical Genetics 04/2014; 15(1):44. · 2.54 Impact Factor
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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.
    The Journal of molecular diagnostics: JMD 10/2013; · 3.48 Impact Factor
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    International journal of cardiology 07/2013; · 6.18 Impact Factor
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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.
    Future Cardiology 07/2013; 9(4):519-34.
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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.
    Journal of Cardiovascular Medicine 06/2013; · 2.66 Impact Factor
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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.
    Orphanet Journal of Rare Diseases 06/2013; 8(1):91. · 4.32 Impact Factor
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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.
    Pediatric Cardiology 04/2013; · 1.20 Impact Factor
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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.
    Heart Failure Clinics 04/2013; 9(2):207-16.
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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.
    Journal of the American College of Cardiology 03/2013; · 14.09 Impact Factor
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    ABSTRACT: BACKGROUND: The right heart is a major determinant of prognosis in cardiac transplant recipient patients. AIM: To investigate right ventricular morphology and function and their relationship with exercise capacity in cardiac transplant recipient patients using standard tranthoracic echocardiography and a new three-dimensional echocardiographic software adapted for right ventricular analysis. METHODS: One hundred fifteen relatively stable cardiac transplant recipient patients (71 men; 58.3 ± 5.8 years; 7.8 ± 4.5 years after transplantation) and 80 healthy age-comparable and sex-comparable controls underwent standard echocardiography, tissue Doppler imaging (TDI), and three-dimensional echocardiography, focused on the right ventricular analysis. Along with left heart parameters, right ventricular measurements included end-diastolic diameters at basal and mid-cavity level; base-to-apex length; tricuspid annulus plane systolic excursion (TAPSE); TDI right ventricular systolic peak velocity (Sm); and three-dimensional ejection fraction. Using the peak systolic tricuspid regurgitation velocity (TRV) and the end-diastolic pulmonary regurgitation velocity, the modified Bernoulli equation was used to calculate the pulmonary artery systolic (PASP) and diastolic pressures. Pulmonary artery vascular conductance (PAVC) was estimated by left ventricular stroke volume/4 × (TRV - pulmonary regurgitation velocity). RESULTS: Left ventricular diameters and ejection fraction did not significantly differ between the two groups, whereas mass index was increased in cardiac transplant recipient patients (P < 0.01). Right ventricular diameters were significantly increased (P < 0.001), whereas TAPSE and right ventricular Sm were significantly lower in cardiac transplant recipient patients. Conversely, in cardiac transplant recipient patients, three-dimensional right ventricular ejection fraction (RVEF) was not significantly reduced (P < 0.001), whereas both PASP and PAVC were impaired. By multivariable analysis, age at transplantation (P < 0.01) and pulmonary artery mean pressure (P < 0.001) were the only independent determinants of right ventricular diameters and RVEF in cardiac transplant. Furthermore, RVEF measured by real-time three-dimensional echocardiography was a powerful independent determinant of functional capacity in cardiac transplant recipient patients. CONCLUSION: Despite the reduction of right ventricular performance along the long axis suggested by TAPSE and right ventricular Sm, the increased right ventricular diameters along with absence of a decrease in three-dimensional RVEF support the hypothesis of geometrical rather than functional changes of the right ventricle in cardiac transplant recipient patients.
    Journal of Cardiovascular Medicine 02/2013; · 2.66 Impact Factor
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    Dataset: MECKI score
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    International journal of cardiology 12/2012; · 6.18 Impact Factor
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    ABSTRACT: Factors that compete to establish heart failure (HF) are not completely known. In the last years the several technological improvements allowed us to deeply study the molecular and genetic aspects of this complex syndrome. This new approach to HF based on molecular biology new discoveries shows us more clearly the pathophysiological bases of this disease, and a future scenery where the genetics may be useful in the clinical practice, as screening of high risk populations, as well as in the diagnosis and therapy of underlying myocardial diseases. The purpose of this review was to analyse the molecular, genetic and epigenetic factors of HF. We described the molecular anatomy of the sarcomere and the pathogenesis of the heart muscle diseases, abandoning the previous monogenic theory for the concept of a polygenic disease. Different actors play a role to cause the illness by themselves, modifying the expression of the disease and, eventually, the prognosis of the patient.
    Minerva cardioangiologica 12/2012; 60(6):593-609. · 0.43 Impact Factor
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    ABSTRACT: BACKGROUND: Our objective was to explore the right ventricular (RV) dimensions and function and the effect of long-term intensive training in a large population of top level athletes using real-time three-dimensional (3D) echocardiography. METHODS: A total of 430 top-level athletes (220 endurance-trained athletes [ETAs] and 210 strength-trained athletes; 265 men [61.6%]; mean age 27.4 ± 10.1 years, range 18-40) and 250 healthy controls underwent a transthoracic echocardiographic examination. Three-dimensional RV measurements included serial short-axis reconstructions of the RV volumetric data sets, and the RV endocardial contour was traced with cross-reference to the long-axis images for identification of the tricuspid annulus. The end-diastolic and end-systolic RV volumes and ejection fraction were calculated off-line using the method of the summation of discs. RESULTS: The strength-trained athletes had a greater heart rate, body surface area, and systolic blood pressure at rest than the ETAs and controls. All RV diameters and 3D volumes and all transmitral and transtricuspid Doppler indexes were greater in the ETAs. Also, the left ventricular stroke volume, cardiac index, and pulmonary artery systolic pressure were greater in the ETAs, and all two-dimensional and 3D RV systolic indexes were comparable. On univariate analysis, the 3D RV end-diastolic volume was significantly associated with advanced age, male gender, duration of training, endurance training, increased left ventricular stroke volume, and pulmonary artery systolic pressure. On multivariate analysis, in the overall study population, the type and duration of training (P < .01), pulmonary artery systolic pressure (P < .01), and left ventricular stroke volume (P < .001) were the only independent predictors of RV end-diastolic volume. CONCLUSIONS: The results of the present study have delineated the upper limits of the RV dimensions in highly trained athletes as measured by real-time 3D echocardiography. The RV end-diastolic volume was significantly greater in the ETA than in the strength-trained athletes and controls.
    Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 08/2012; · 2.98 Impact Factor
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    ABSTRACT: Systematic clinical assessment and careful monitoring of patients with hypertrophic cardiomyopathy (HCM) can be used to identify a cohort of patients that benefit from medical intervention and almost certainly improve long-term outcomes. One of the major limitations of the current approach is a lack of predictive power of individual risk factors, which means that many patients receive therapy. The aim of this review is to highlight other aspects of the disease, assessed using old and new medical technologies, that appear to provide new prognostic information. The hope for the future is that their incorporation in new risk algorithms will improve treatment for all HCM patients with the disease, irrespective of their vulnerability to adverse complications.
    Journal of Cardiovascular Medicine 08/2012; · 2.66 Impact Factor
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    ABSTRACT: Few data are available on cardiac morphology and function in children with heterozygous familial hypercholesterolemia (FH). Such patients represent a unique clinical model to assess the effect of pure hypercholesterolemia on cardiac morphology and function, excluding the effect of comorbidities. Speckle-tracking echocardiography, a relatively new echocardiographic modality, allows the assessment of myocardial deformation properties. The aim of this study was to define in children with FH the preclinical effects of isolated hypercholesterolemia on the cardiovascular system by examining left ventricular (LV) function using speckle-tracking echocardiography. Ninety children (45 with FH and 45 controls; mean age, 11 ± 3 years) were prospectively studied. Children with FH showed thicker LV walls and significantly higher LV mass indexed for height(2.7) (P = .0008) and for body surface area (P < .0001). LV ejection fractions were similar in both groups. Assessment of diastolic function demonstrated longer deceleration times (P < .0001), reduced early diastolic mitral annular velocities (P < .0001), and higher transmitral early/early diastolic mitral annular velocity ratios (P = .0003) in children with FH. Longitudinal and circumferential myocardial deformation of the left ventricle were significantly reduced (P < .0001) whereas radial deformation was increased in children with FH (P = .04) compared with controls. This study demonstrates that hypercholesterolemia is associated with significant LV morphologic and functional alterations during childhood. The findings also suggest that reductions in longitudinal and circumferential deformation are compensated for by increasing radial strain in children with FH with normal LV ejection fractions. This study raises the questions of the clinical importance of these findings and the opportunity for cholesterol-lowering therapy. The potential benefits and risks of such treatment at a young age need to be addressed in larger long-term studies.
    Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 08/2012; 25(10):1075-82. · 2.98 Impact Factor
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    ABSTRACT: OBJECTIVES: We built and validated a new heart failure (HF) prognostic model which integrates cardiopulmonary exercise test (CPET) parameters with easy-to-obtain clinical, laboratory, and echocardiographic variables. BACKGROUND: HF prognostication is a challenging medical judgment, constrained by a magnitude of uncertainty. METHODS: Our risk model was derived from a cohort of 2716 systolic HF patients followed in 13 Italian centers. Median follow up was 1041days (range 4-5185). Cox proportional hazard regression analysis with stepwise selection of variables was used, followed by cross-validation procedure. The study end-point was a composite of cardiovascular death and urgent heart transplant. RESULTS: Six variables (hemoglobin, Na(+), kidney function by means of MDRD, left ventricle ejection fraction [echocardiography], peak oxygen consumption [% pred] and VE/VCO(2) slope) out of the several evaluated resulted independently related to prognosis. A score was built from Metabolic Exercise Cardiac Kidney Indexes, the MECKI score, which identified the risk of study end-point with AUC values of 0.804 (0.754-0.852) at 1year, 0.789 (0.750-0.828) at 2years, 0.762 (0.726-0.799) at 3years and 0.760 (0.724-0.796) at 4years. CONCLUSIONS: This is the first large-scale multicenter study where a prognostic score, the MECKI score, has been built for systolic HF patients considering CPET data combined with clinical, laboratory and echocardiographic measurements. In the present population, the MECKI score has been successfully validated, performing very high AUC.
    International journal of cardiology 07/2012; · 6.18 Impact Factor
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    ABSTRACT: Aortic regurgitation (AR) has increased in the pediatric population because of the expanded use of new surgical and hemodynamic procedures. Unfortunately, the exact timing for operation in patients with AR is still debated. Conventional echocardiographic parameters, left ventricular (LV) dimensions and the LV ejection fraction, have limitations in predicting early LV dysfunction. Two-dimensional strain imaging, an emerging ultrasound technology, has the potential to better study those patients. The aim of this study was to assess the prognostic value of 2-dimensional longitudinal strain in young patients with congenital isolated moderate to severe AR. Twenty-six young patients with asymptomatic AR (aged 3 to 16 years) were studied. The mean follow-up duration was 2.9 ± 1.2 years (range 0.5 to 6). Baseline LV function by speckle-tracking and conventional echocardiography in patients with stable disease was compared with that in patients with progressive AR (defined as development of symptoms, increase in LV volume ≥15%, or decrease in the LV ejection fraction ≤10% during follow-up). LV ejection fractions were similar between groups. The jet area/LV outflow tract area ratio was significantly increased in patients with AR with progressive disease (31.2 ± 5.6% vs 39.2 ± 3.8%, p <0.001). The peak transmitral early velocity/early diastolic mitral annular velocity ratio was significantly increased in patients with progressive AR (p = 0.001). LV average longitudinal strain was significantly reduced in patients with progressive AR compared to those with stable AR (-17.8 ± 3.9% vs -22.7 ± 2.7%, p = 0.001). On multivariate analysis, the only significant risk factor for progressive AR was average LV longitudinal strain (p = 0.04, cut-off value >-19.5%, sensitivity 77.8%, specificity 94.1%, area under the curve 0.889). In conclusion, 2-dimensional strain imaging can discriminate young asymptomatic patients with progressive AR. This could allow young patients with AR to have a better definition of surgical timing before the occurrence of irreversible myocardial damage.
    The American journal of cardiology 06/2012; 110(7):1051-5. · 3.58 Impact Factor

Publication Stats

1k Citations
456.52 Total Impact Points

Institutions

  • 2011–2013
    • AORN Ospedali dei Colli
      Cicciano, Campania, Italy
    • University of Quindio
      Armenia, Quindío, Colombia
  • 1998–2013
    • Second University of Naples
      • Faculty of Medicine and Surgery
      Caserta, Campania, Italy
  • 1995–2012
    • Monaldi Hospital
      Napoli, Campania, Italy
  • 2004
    • Ospedale Pediatrico Bambino Gesù
      • Department of Pediatric Cardiology and Cardiac Surgery
      Roma, Latium, Italy
  • 2003
    • Università degli Studi di Torino
      • Dipartimento di Scienze Mediche
      Torino, Piedmont, Italy
  • 1997–2002
    • University of Naples Federico II
      • Department of Molecular Medicine and Medical Biotechnology
      Napoli, Campania, Italy