[Cardiologists and mucopolysaccharidoses. Recommendations of GICEM (Cardiology Experts on Metabolic Disease Italian Group) for diagnosis, follow-up and cardiological management]. / Il cardiologo e le mucopolisaccaridosi. Raccomandazioni del GICEM (Gruppo Italiano Cardiologi Esperti Malattie Metaboliche) su diagnosi, follow-up e management cardiologico.

Mucopolysaccharidoses (MPS) represent a group of rare lysosomal storage disorders, with a heterogeneous clinical presentation in terms of inheritance (autosomal and X-linked recessive), age of onset (infants, children, and adults), systemic and cardiac manifestations (mild to severe disease forms). Evidence-based recommendations on the diagnosis and management of cardiovascular disease in MPS are scarce. GICEM (Gruppo Italiano Cardiologi Esperti Malattie Metaboliche) is a group of cardiologists, cardiac surgeons and pediatricians with a specific expertise in metabolic diseases including MPS. In this paper, we report our experience and recommendations on the diagnosis and management of cardiovascular aspects in MPS, with a tailored approach based on current evidence, and taking into account MPS phenotype (particularly, I, II, IVa, VI), age at presentation, and severity of systemic and cardiac manifestations.

Prehypertension in adolescents with cardiovascular risk: a comparison between type 1 diabetic patients and overweight subjects.

BACKGROUND: Adolescents with type 1 diabetes and obesity present higher cardiovascular risk and ambulatory blood pressure measurements (ABPM) has been shown to predict vascular events, especially by identifying the nondipper status. The aim of our observational cross-sectional study conducted in adolescents with type 1 diabetes, overweight subjects and healthy controls was to assess mean blood pressure parameters to identify subclinical cardiovascular risk. METHODS: The study included adolescents patients with type 1 diabetes followed in our Pediatric Department in University of Catania between January 2011 and 2013. A total of 60 patients were enrolled, and 48 (32 male and 16 female) completed the study. For each subject we performed systolic and diastolic Ambulatory Blood Pressure Measurements (ABPM) during wakefulness and sleep recording blood pressure every 30 min for 24 h with the Tonoport V/2 GE CardioSoft V6.51 device. We compared the data of patients with those of overweight subjects and healthy controls. RESULTS: ABPM revealed no significant difference between type 1 diabetic patients and overweight subjects in 24 h Systolic, 24 h Diastolic, Day-time Systolic, Night-time systolic and Day-time Diastolic blood pressure values but significantly different values in Night-time Diastolic blood pressure values (p < 0.001). We found significant differences between type 1 diabetic patients and healthy controls in all 24 h Systolic (p < 0.001), 24 h Diastolic (p < 0.01), Day-time Systolic (p < 0.01), Night-time Systolic (p < 0.001), Day-time Diastolic (p < 0.05) and Night-time Diastolic (p < 0.001) blood pressure values. We detected hypertension in 12/48 (25%) type 1 diabetic patients and in 10/48 overweight subjects (p = 0.62; OR 1.2; CI 0.48-3.29), whereas no-one of healthy controls presented hypertension (p < 0.001). We observed nondipper pattern in 40/48 (83.3%) type 1 diabetic patients, in 33/48 (68.8%) overweight subjects (p = 0.094; OR 2.27; CI 0.85-6.01), and in 16/48 (33.3%) of healthy controls (p < 0.001; OR 10; CI 3.79-26.3). CONCLUSIONS: ABPM studies might help to define a subset of patients at increased risk for the development of hypertension. In evaluating blood pressure in type 1 diabetes and overweight subjects, ABPM should be used since a reduced dipping can indicate incipient hypertension.

Molecular physiopathogenetic mechanisms and development of new potential therapeutic strategies in persistent pulmonary hypertension of the newborn.

Persistent pulmonary hypertension of the newborn (PPHN) is a cyanogenic plurifactorial disorder characterized by failed postnatal drop of pulmonary vascular resistance and maintenance of right-to-left shunt across ductus arteriosus and foramen ovale typical of intrauterine life. The pathogenesis of PPHN is very complex and can result from functional (vasoconstriction) or structural (arteriolar remodeling, reduced pulmonary vessels density) anomalies of pulmonary circulation. Etiopathogenetic factors heterogeneity can strongly condition therapeutical results and prognosis of PPHN that is particularly severe in organic forms that are usually refractory to selective pulmonary vasodilator therapy with inhaled nitric oxide. This paper reports the more recent acquisitions on molecular physiopathogenetic mechanisms underlying functional and structural forms of PPHN and illustrates the bases for adoption of new potential treatment strategies for organic PPHN. These strategies aim to reverse pulmonary vascular remodeling in PPHN with arteriolar smooth muscle hypertrophy and stimulate pulmonary vascular and alveolar growth in PPHN associated with lung hypoplasia.In order to restore lung growth in this severe form of PPHN, attention is focused on the results of studies of mesenchymal stem cells and their therapeutical paracrine effects on bronchopulmonry dysplasia, a chronic neonatal lung disease characterized by arrested vascular and alveolar growth and development of pulmonary hypertension.

Heart involvement in children and adults with cystic fibrosis: correlation with pulmonary indexes and inflammation markers.

BACKGROUND: Cardiovascular involvement in Cystic Fibrosis (CF) is a not rare condition, although the prevalence of subclinical pulmonary hypertension (PH) and cardiac dysfunction is not known in the early stages of CF progression. The aim of our study was to assess cardiac involvement in children and adults affected by cystic fibrosis compared with healthy subjects of same age using echocardiography. METHODS: Fifty-five patients, 25 adults and 30 children completed the study. We assessed FEV1 (Forced Expiratory Volume in one second), and carried out colour Doppler-echocardiography evaluating ejection fraction (EF) measurement of left ventricle, tricuspid annular plane systolic excursion (TAPSE) of right ventricle and pulmonary artery pressure (PAP). We compared the auxological, respiratory and cardiologic data with those of 16 adults and 34 children of the same age. RESULTS: We discovered significantly different values of PAP between patients and controls in both children (p = 0.0001, r=- 0.62) and adults (p=0.0001, r=- 0.63), whereas the EF and TAPSE showed significantly different values in only adults (p=0.0023 and p=0.0194 respectively). We found in both children and adults with CF an inverse correlation between PAP and FEV1 (p=0.000, p=0.001), Erythrocyte Sedimentation Rate (ESR) and FEV 1 (p=0.015, r=- 0.43; p=0.009, r=- 0.51), and highly sensitive C-reactive protein (hs-CRP) and FEV 1 (p=0.007, r=- 0.48; p=0.001, r=- 0.60). In adults we also detected direct correlation between PAP and hs-CRP (p=0.008, r=0.51) and PAP and ESR (p=0.009, r=0.51). CONCLUSIONS: In paediatric-aged CF patients there are already early signs of potential heart impairment, represented by an increase of pulmonary blood pressure, and in adult age the systolic function of right ventricle may be impaired. We hypothesise that such cardiac impairments may gradually arise due to preceding chronic inflammation related to prior degeneration of lung function and thus it is very important to keep patients clinically stable and address chronic inflammation as early as possible in the progression of CF.

Effects of Sustained Lung Inflation, a lung recruitment maneuver in primary acute respiratory distress syndrome, in respiratory and cerebral outcomes in preterm infants.

BACKGROUND: Sustained Lung Inflation (SLI) is a maneuver of lung recruitment in preterm newborns at birth that can facilitate the achieving of larger inflation volumes, leading to the clearance of lung fluid and formation of functional residual capacity (FRC). AIM: To investigate if Sustained Lung Inflation (SLI) reduces the need of invasive procedures and iatrogenic risks. STUDY DESIGN: 78 newborns (gestational age≤34 weeks, weighing≤2000 g) who didn't breathe adequately at birth and needed to receive SLI in addition to other resuscitation maneuvers (2010 guidelines). SUBJECTS: 78 preterm infants born one after the other in our department of Neonatology of Catania University from 2010 to 2012. OUTCOME MEASURES: The need of intubation and surfactant, the ventilation required, radiological signs, the incidence of intraventricular hemorrhage (IVH), periventricular leukomalacia, retinopathy in prematurity from III to IV plus grades, bronchopulmonary dysplasia, patent ductus arteriosus, pneumothorax and necrotizing enterocolitis. RESULTS: In the SLI group infants needed less intubation in the delivery room (6% vs 21%; p<0.01), less invasive mechanical ventilation (14% vs 55%; p≤0.001) and shorter duration of ventilation (9.1 days vs 13.8 days; p≤0.001). There wasn't any difference for nasal continuous positive airway pressure (82% vs 77%; p=0.43); but there was less surfactant administration (54% vs 85%; p≤0.001) and more infants received INSURE (40% vs 29%; p=0.17). We didn't found any differences in the outcomes, except for more mild intraventricular hemorrhage in the SLI group (23% vs 14%; p=0.15; OR=1.83). CONCLUSION: SLI is easier to perform even with a single operator, it reduces the necessity of more complicated maneuvers and surfactant without statistically evident adverse effects.

Assessment of coronary artery intimal thickening in patients with a previous diagnosis of Kawasaki disease by using high resolution transthoracic echocardiography: our experience.

BACKGROUND: Kawasaki disease (KD) is a generalized systemic vasculitis of unknown etiology involving medium and small size blood vessels, particularly the coronary arteries. In these vessels a progressive stenosis may result from active remodeling with an intimal proliferation and neoangiogenesis. The aim of our study was to assess, by using high-resolution transthoracic 2D Echocardiography, if subjects with a previous diagnosis of Kawasaki disease after several years show a coronary intimal thickening, suggestive of a persistent cardiovascular risk. METHODS: We assessed measurement of thickening, inner diameter and outer diameter of coronary arteries using 2D Echocardiography (Philips E 33 with multy-frequency S8-3 and S12-4 probes) and examining the proximal portion of left main coronary artery just above the aortic valve with parasternal short axis view. RESULTS: We found a significant intimal thickening in patients with previous Kawasaki disease compared to healthy controls. In particular, we noticed that also subjects not suffering from coronary impairment in acute phase have higher values of thickening than healthy controls, and this wall thickening may confer a higher cardiovascular risk. CONCLUSIONS: Therefore we concluded that the assessment of coronary artery thickening by high-resolution transthoracic 2D Echocardiography may become an essential instrument to evaluate late cardiovascular risk in subjects with a diagnosis of Kawasaki disease in childhood.

Rhabdomyomas and tuberous sclerosis complex: our experience in 33 cases.

BACKGROUND: Rhabdomyomas are the most common type of cardiac tumors in children. Anatomically, they can be considered as hamartomas. They are usually randomly diagnosed antenatally or postnatally sometimes presenting in the neonatal period with haemodynamic compromise or severe arrhythmias although most neonatal cases remain asymptomatic. Typically rhabdomyomas are multiple lesions and usually regress spontaneously but are often associated with tuberous sclerosis complex (TSC), an autosomal dominant multisystem disorder caused by mutations in either of the two genes, TSC1 or TSC2. Diagnosis of tuberous sclerosis is usually made on clinical grounds and eventually confirmed by a genetic test by searching for TSC genes mutations. METHODS: We report our experience on 33 cases affected with rhabdomyomas and diagnosed from January 1989 to December 2012, focusing on the cardiac outcome and on association with the signs of tuberous sclerosis complex. We performed echocardiography using initially a Philips Sonos 2500 with a 7,5/5 probe and in the last 4 years a Philips IE33 with a S12-4 probe. We investigated the family history, brain, skin, kidney and retinal lesions, development of seizures, and neuropsychiatric disorders. RESULTS: At diagnosis we detected 205 masses, mostly localized in interventricular septum, right ventricle and left ventricle. Only in 4 babies (12%) the presence of a mass caused a significant obstruction. A baby, with an enormous septal rhabdomyoma associated to multiple rhabdomyomas in both right and left ventricular walls died just after birth due to severe heart failure. During follow-up we observed a reduction of rhabdomyomas in terms of both number and size in all 32 surviving patients except in one child. Eight patients (24,2%) had an arrhythmia and in 2 of these cases rhabdomyomas led to Wolf-Parkinson-White Syndrome. For all patients the arrhythmia spontaneously totally disappeared or was reduced gradually. With regarding to association with tuberous sclerosis, we diagnosed tuberous sclerosis clinically in 31 babies (93,9%). CONCLUSION: Rhabdobyomas are tumors with favorable prognosis because they frequently do not cause symptoms and they often regress in numbers and size. Nevertheless, due to frequent association with tuberous sclerosis complex and the resulting neurological impairment, the prognosis can result unfavorable.

Severe Kawasaki disease in a 3-month-old patient: a case report.

BACKGROUND: Kawasaki disease is a multi-system vasculitis which usually occurs in children under 5 years of age. In infants under three months of age, it is very rare and usually associated with a high incidence of incomplete or atypical forms, often unresponsive to treatment. This condition increases the risk of cardiovascular complications such as coronary artery aneurysms. CASE PRESENTATION: We describe a 3-month-old infant who developed early and severe aneurysms in three coronary arteries despite a timely administration of intravenous immunoglobulins, followed by three days of intravenous methylprednisolone. CONCLUSION: This case report underlines that the development of coronary artery aneurysm correlates with a delayed diagnosis and treatment, incomplete or atypical forms of the disease, and additionally the severity of clinical presentation, especially in cases of very young infants below 3 months of age. Our case is notable because of the very young age of the patient, the severity of clinical presentation with an early development of coronary artery aneurysms and the unresponsiveness to the therapy.

Molecular pathogenesis of myocardial remodeling and new potential therapeutic targets in chronic heart failure.

It is well known that the natural history of chronic heart failure (CHF),regardless of age and aetiology,is characterized by progressive cardiac dysfunction refractory to conventional cardiokinetic, diuretic and peripheral vasodilator therapy. Several previous studies, both in animals and humans, showed that the key pathogenetic element of CHF negative clinical evolution is constituted by myocardial remodeling. This is a complex pathologic process of ultrastructural rearrangement of the heart induced by various neuro-humoral factors released by cardiac fibrocells in response to biomechanical stress connected to chronic haemodynamic overload. Typical features of myocardial remodeling are represented by cardiomyocytes hypertrophy and apoptosis, extracellular matrix alterations, mesenchymal fibrotic and phlogistic processes and by cardiac gene expression modifications with fetal genetic program reactivation. In the last years, increasing knowledge of subtle molecular and cellular mechanisms involved in myocardial remodeling has led to the discovery of some new potential therapeutic targets capable of inducing its regression. In this paper our attention is focused on the possible use of antiapoptotic and antifibrotic agents, and on the fascinating perspectives offered by the development of myocardial gene therapy and, in particular, by myocardial regenerative therapy.

Pentraxin-3 in late-preterm newborns with hypoxic respiratory failure.

The aim of this study was: echocardiographical assessment of cardiac alterations in late-preterm newborns with hypoxic respiratory failure (HRF), and, study serum pentraxin-3 (PTX-3) in relation to the severity of respiratory impairment and to some echocardiographic parameters (i.e. ejection fraction (EF), stroke volume (SV) and cardiac output (CO). We enrolled in this study 40 newborn infants whose 22 (group I) with moderate HRF and 18 (group II) with severe HRF. In group I the mean values of EF, SV and CO were significantly higher than in the group II. Our results showed a significant increase of PTX-3 in group II patients at 24h of life when compared to group I. Taking patients all together (n=40), we found a significant (R=-73) reverse correlation between EF and serum values of PTX-3. PTX-3 in our patients with HRF is affected by the severity of the hypoxic insult and correlate with the cardio-vascular impairment.

[Perforated jejunal diverticulum: a rare cause of acute abdomen]. / Il diverticolo digiunale perforato: una rara causa di addome acuto.

Jejunal diverticulum is an uncommon, acquired condition, and the majority of patients are usually asymptomatic. Jejunal diverticula become clinically relevant when complications, such as diverticulitis, intestinal bleeding, obstruction, or perforation occur. A rare case of acute abdomen due to a perforated jejunal diverticulum is presented. The diagnosis was initially suggested by CT and confirmed intraoperatively when a 74-year-old male patient underwent a segmental jejunal resection with primary anastomosis. A review of the literature indicates the rarity of this condition, and therefore the aetiology, pathogenesis, diagnosis, and management are briefly discussed. An early diagnosis, based on ultrasonography and CT, and consequently prompt resection of the jejunum affected are the keys to a successful outcome. Because a longer duration of symptoms before operation correlates with a worse prognosis, the possibility of a clinical diagnosis of perforated jejunal diverticulum should be entertained as part of any evaluation of acute abdomen, especially in the elderly.