Giovanna Bosco

Aorta and coronary angiographic follow-up of children with severe hypercholesterolemia treated with low-density lipoprotein apheresis

BACKGROUND: In this single‐center, nonrandomized, prospective study, 11 children with severe genetic hypercholesterolemia, without previous cardiovascular disease events, were treated with low‐density lipoprotein apheresis (LDLa).

A three month-old infant with severe hyperchylomicronemia: Molecular diagnosis and extracorporeal treatment

OBJECTIVE Chylomicronemia syndrome presenting in childhood is a rare recessive disorder due to mutations of lipoprotein lipase (LPL) and more rarely of APOC2, APOA5, GPIHBP1 or LMF1 genes. It often requires urgent and suitable treatment to avoid acute pancreatitis. The aim of this study was the molecular characterization and treatment of a 3 month-old infant with plasma triglycerides (TG) > 300 mmol/L. METHODS All candidate genes were sequenced. The patient was submitted to one plasma-exchange (PEX) procedure and subsequently to a rigid lipid-lowering diet (milk: Monogen(®)). RESULTS The proband was homozygous for a novel LPL mutation (c.242G > A, p.G81D) which in silico results pathogenic. After PEX, which was well tolerated, TG dropped to 64 mmol/L. During 5-month follow-up there was a clear trend towards lower and stable TG values. CONCLUSION PEX is applicable in subjects with very low body weight when the extreme severity of the clinical picture has no therapeutic alternatives.

Low-density lipoprotein apheresis in a patient aged 3.5 years.

A 3.5 y‐old girl carrying a severe mutation of the LDL‐receptor gene known as “FH Pavia”, affected by homozygous familial hypercholesterolemia (FH), and at high risk of developing coronary artery atherosclerosis was treated with selective dextran sulphate cellulose (DSC) column low‐density lipoprotein apheresis (LDL‐a). This is the youngest patient ever treated with LDL‐a. Plasma total cholesterol (982 mg/dl) and LDL‐cholesterol (939mg/dl) (T‐Chol, LDL‐Chol) levels at baseline showed a transient decrease: –13.4%, and –16.8%, respectively, after 9 mo of combined treatment with a diet, cholestyramine (max. 12g/d) and atorvastatin (max. 30mg/d). However, the drugs were discontinued because of intolerance and an increase in aminotransferases and creatine phosphokinase in the plasma. Moreover, after 9 mo of this therapy, the mean plasma T‐Chol and LDL‐Chol levels were still high (930 mg/dl and 869.5 mg/dl, respectively). Therefore, 9 consecutive treatments with LDL‐a were carried out every 15 d (plasma volumes treated: 1000–1700 ml). Mean plasma T‐Chol, LDL‐Chol, triglycerides (TG), and Lp(a) decreased significantly: –75.5%, –77.2%, –67.5% and −50.8%, respectively. HDL‐cholesterol (HDL‐Chol) concentration was considerably decreased immediately after apheresis because of haemodilution (X: −45.1%).

Molecular analysis of PRKAG2, LAMP2, and NKX2‐5 genes in a cohort of 125 patients with accessory atrioventricular connection

Molecular Analysis of PRKAG2, LAMP2, and NKX2-5 Genes in a Cohort of 125 Patients With Accessory Atrioventricular Connection Giorgia Esposito, Giorgia Grutter, Fabrizio Drago, Mauro W. Costa, Antonella De Santis, Giovanna Bosco, Bruno Marino, Emanuele Bellacchio, Francesca Lepri, Richard P. Harvey, Anna Sarkozy,* and Bruno Dallapiccola IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, Rome, Italy Casa Sollievo della Sofferenza-Mendel Institute, Rome, Italy Department of Experimental Medicine and Pathology, University ‘‘La Sapienza’’, Rome, Italy Department of Pediatric Cardiology, Bambino Gesu? Hospital, IRCCS, Rome, Italy Victor Chang Cardiac Research Institute, Darlinghurst, Sydney, Australia Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil Section of Pediatric Cardiology, Department of Pediatrics, University ‘‘La Sapienza’’, Rome, Italy

Blocked Atrial Bi/Trigeminy In Utero Evolving in Supraventricular Tachycardia after Birth

Transient episodes of fetal bradycardia (heart rate less than 110 bpm) are usually benign and typically result from increased vagal stimulation in the fetus. Causes of sustained fetal bradycardia include sinus bradycardia, blocked atrial bigeminy/trigeminy, high-degree atrioventricular block, and long QT syndrome. We present the case of a 34-year-old Caucasian patient referred to our department for “blocked atrial bigeminy with pseudobradycardia” detected elsewhere at 33 weeks of gestation. A fetal echocardiography showed during all the examination a blocked atrial trigeminy with a mean fetal heart rate of 100 bpm. After birth three subsequent ECGs until day 3 showed no evidence of atrial extrasystoles, confirming the well-known frequent regression of this kind of fetal benign arrhythmia, but on day 11 recurrence of supraventricular trigeminy and development of episodes of paroxystic supraventricular tachycardia were observed. On the basis of this observation, we recommend that fetuses with complex atrial ectopic beats should be closely monitored before and after birth for evidence of new arrhythmias.

Effects of Exercise on Arrhythmia (and Viceversa): Lesson from the Greek Mythology

Exercise represents an important lifestyle factor in all human ages when felt in harmony with other psycho-physical and environmental variables that affect individual life (e. g. quality of interest, affections, environment, diet and food). Consequently, in addition to the training level, the amount, intensity and modality of exercise (ana-/aerobic, isometric/isotonic), need to be personalized, considering the underlying diseases, which may benefit from it or worsening.Greek mythology gives us good examples of the exercise concepts evolution.From Discus-thrower to Spear-carrier the idea of physical activity is more effectively expressed. The Myron Discobolus displays the enduring pattern of athletic energy translated into the dynamic force given by the exercise. In Doryphoros instead, the physical activity is oriented to the achievement of the required psyco-physical harmony, whos the concept is aimed of being expressed by the sculpture.As outlined below, even in the field of arrhythmia, scientific evidence as well as clinical experience, supports the same concept: physical activity may be important while safely managed and personalized.

Torsade de pointes : an unknown complication of hypertensive encephalopathy

Sir: Torsade de pointes (TdP) is a distinctive form of ventricular tachycardia commonly associated with congenital or acquired long QT syndrome. The acquired form is usually secondary to the use of antiarrhythmic drugs or other noncardiac agents, although it can also be precipitated by electrolyte imbalance, heart disease, endocrine disorders, and any of several intracranial conditions [1]. We report here the unusual association of long QT syndrome and TdP with hypertensive encephalopathy in a 9-yearold child with poststreptococcal glomerulonephritis. The patient was referred to our pediatric intensive care unit because of hypertension (blood pressure: 198/130mmHg), bradycardia, seizures and mental confusion. Magnetic resonance imaging (MRI) of the brain showed typical signs of posterior reversible encephalopathy. Laboratory tests suggested poststreptococcal glomerulonephritis (high ASO titers, low C3, normal C4, mild anemia, elevated blood urea nitrogen, decreased serum protein levels, hematuria, proteinuria). Treatment with nitroprusside and mannitol was therefore thus started to lower blood pressure by 20% a day and to relieve brain edema. On admission the child underwent complete heart screening. ECG showed a sinus rhythm with a ventricular rate of 58 bpm and a corrected QT interval (QTc) of 400 ms. Two-dimensional echocardiography showed mild left ventricular enlargement and moderate aortic and mitral valve regurgitation. Because these echocardiographic changes were the patient’s only manifestations compatible with acute rheumatic fever they were considered secondary to the severe systemic hypertension [2]. Thirty-six hours after admission, despite treatment with nitroprusside, the patient experienced an episode of marked agitation associated with a sudden increase in blood pressure (to 160/100mmHg) and loss of consciousness. Central pulses were not palpable and the child was therefore resuscitated and mechanically ventilated. Electrocardiography (ECG) during the episode showed a typical tracing of TdP (Fig. 1a). TdP rapidly

4.P.411 Diet only and diet plus simvastatin in the treatment of heterozygous familial hypercholesterolemia in childhood

This study was a 1-year clinical study on 16 (7 males and 9 females) pediatric patients with heterozygous familial hypercholesterolemia treated with hypocholesterolemic diet only, or with diet plus drug (simvastatin 10 mg/day). According to the study protocol, the children were submitted to a 3-month washout (free diet). Then they were given a diet (American Heart Association, step 2) for 6 months. After 6 months they were divided into two groups matched for sex, age and body mass index (BMI). Diet only was given to group A (n = 8); simvastatin (10 mg/daily) was given to group B, for 1 year. All patients were examined at baseline, and monitored for safety during the study by pediatricians. All patients were submitted to noninvasive cardiovascular examinations (exercise electrocardiogram, echocardiography). After 12 months of treatment with simvastatin, total cholesterol (TC) and low density lipoprotein cholesterol (LDLC) showed a statistically significant reduction (group B). The decrease of TC and LDLC in patients on diet only was 4% and 3% (all) and 17% and 4% (group A) after 6 and 12 months, respectively.

Permanent Mechanical Catheter Ablation of an Accessory Pathway in a Child

Permanent mechanical ablation of an accessory atrioventricular pathway was observed in an infant during intracavitary electrophysiological mapping. The persistent lack of preexcitation was confirmed during a 15‐month follow‐up period.