Angelica Bibiana Delogu

Clinical and Molecular Characterization of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia

Background—Mutations in the cardiac ryanodine receptor gene (RyR2) underlie catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmogenic disease occurring in the structurally intact heart. The proportion of patients with CPVT carrying RyR2 mutations is unknown, and the clinical features of RyR2-CPVT as compared with nongenotyped CPVT are undefined. Methods and Results—Patients with documented polymorphic ventricular arrhythmias occurring during physical or emotional stress with a normal heart entered the study. The clinical phenotype of the 30 probands and of 118 family members was evaluated, and mutation screening on the RyR2 gene was performed. Arrhythmias documented in probands were: 14 of 30 bidirectional ventricular tachycardia, 12 of 30 polymorphic ventricular tachycardia, and 4 of 30 catecholaminergic idiopathic ventricular fibrillation;RyR2 mutations were identified in 14 of 30 probands (36% bidirectional ventricular tachycardia, 58% polymorphic ventricular tachycardia, 50% catecholaminergic idiopathic ventricular fibrillation) and in 9 family members (4 silent gene carriers). Genotype-phenotype analysis showed that patients with RyR2 CPVT have events at a younger age than do patients with nongenotyped CPVT and that male sex is a risk factor for syncope in RyR2-CPVT (relative risk=4.2). Conclusions—CPVT is a clinically and genetically heterogeneous disease manifesting beyond pediatric age with a spectrum of polymorphic arrhythmias. &bgr;-Blockers reduce arrhythmias, but in 30% of patients an implantable defibrillator may be required. Genetic analysis identifies two groups of patients: Patients with nongenotyped CPVT are predominantly women and become symptomatic later in life; patients with RyR2 CPVT become symptomatic earlier, and men are at higher risk of cardiac events. These data provide a rationale for prompt evaluation and treatment of young men with RyR2 mutations.

Prophylactic ibuprofen therapy of patent ductus arteriosus in preterm infants.

Abstract This study was aimed at evaluating the efficacy of ibuprofen in the prophylaxis of patent ductus arteriosus (PDA) in very preterm neonates and at detecting eventual side-effects. A total of 46 preterm neonates with gestational age under 31 weeks were randomly assigned at 2 h of life: 23 to the prophylaxis group and 23 to the control group. The prophylaxis group received intravenous treatment with ibuprofen lysine (10 mg/kg), followed by 5 mg/kg after 24 h and 48 h. No placebo was given to the control group. No PDA was demonstrated at 72 h of life in 20 of the 23 babies in the ibuprofen group (87%) nor in 7 of the 23 control neonates (30.4%). All neonates with PDA received treatment with indomethacin. One neonate in the prophylaxis group and three in the control group underwent surgical ligation. Prophylaxis with ibuprofen was not associated with any significant side-effect except for food intolerance. Conclusion Ibuprofen prophylaxis seems to be efficient in closing patent ductus arteriosus and in reducing indomethacin treatment. No significant early side-effects were found due to ibuprofen.

Transcatheter closure of persistent ductus arteriosus with the Amplatzer duct occluder in very young symptomatic children

Objectives: To analyse safety, efficacy, and follow up results of percutaneous closure of persistent ductus arteriosus (PDA) in very young symptomatic children. Patients and design: Between March 2000 and March 2003, of 197 patients treated at the authors’ institution 18 were symptomatic children aged ⩽ 3 years old. Seven of these children were ⩽ 1 year old. Indications for closure were failure to thrive (12 patients) and frequent respiratory infections (six patients). The procedure was carried out under heavy sedation with fluoroscopic control. The Amplatzer duct occluder device was used. Basal physical examinations and echocardiograms were performed before the procedure and at follow up (three, six, and 12 months and yearly thereafter). Results: Mean (SD) age was 18.3 (10) months and mean (SD) weight at closure was 9.1 (2.2) kg. Neither death nor any major complications occurred. Complications occurred in three patients aged ⩽ 1 year. Two patients had a mild inguinal haematoma. One patient had femoral artery thrombosis that was successfully treated by intravenous urokinase. The mean (SD) follow up was 12.8 (8.5) months. No problems occurred. Patients with recurrent respiratory infections had no significant recurrences and children who had failed to thrive had significantly increased growth. Conclusions: In experienced hands, percutaneous closure of moderate to large PDA in very young symptomatic children is safe, effectively closes the PDA, and solves clinical problems.

Role of Heart Rate Variability in the Early Diagnosis of Diabetic Autonomic Neuropathy in Children

Background: Diabetic autonomic neuropathy (DAN) is a major complication of diabetes. DAN has been shown to be closely related to glycemic control. To contribute significantly to the morbidity and mortality of the disease, and to be indicative of an increased risk of cardiovascular events. Tests asssing the function of the autonomic nervous system, such as the response of heart rate and blood pressure to maneuvers stimulating the autonomic nervous system, including deep breathing. Valsalva maneuver and standing, allowed to detect signs of DAN in adolescents; however, the sensitivity of such tests in revealing an early impairment of the autonomic nervous system proved low. Several studies found heart rate variability (HRV) to be useful in assessing the dysfunction of the autonomic nervous system in diabetic children and adolescents, but only few HRV parameters were evaluated in most of them. Objective: To study cardiac autonomic nervous system in diabetic children, and to investigate whether the duration of diabetes and the degree of metabolic control are determinants for the development of DAN in children. Patients and Methods: We analyzed HRV in 50 asymptomatic patients with insulin-dependent diabetes mellitus (IDDM) and 30 healthy children matched for age and sex. Results: Patiens with a history of diabetes > 8 years showed significant alterations of the autonomic nervous systemm (significant reduction of r-MSSD, pNN50, HF and increase in LF/HF). Conversely, only a reduction in pNN50 was found in patients with a disease duration < 8 years. Furthermore, we also observed significant HRV abnormalities in patients with an impaired metabolic control of diabetes. Compared to controls, patients with glycosylated hemoglobin blood levels (HbA1C) > 8% showed a significant reduction of r-MSSD, pHH50 and total power spectrum, whereas no HRV abnormalities were detected in patients with an HbA1C < 8%. Conclusions: HRV analysis can detect early subclinical alterations of the autonomic nervous system in asymptomatic patients with IDDM, which seem to consist mainly in a parasympathetic impairment. Autonomic dysfunction is associated both with the duration and an inadequate metabolic control of the disease.Hintergrund: Die diabetische Polyneuropathie (DAN) ist eine Hauptkomplikation des Diabetes mellitus. Die DAN zeigt eine enge Beziehung zur Kontrolle der Blutzuckerwerte und trägt signifikant zur Morbidität und Letalität der Erkrankung bei und weist auf eine erhöhte kardiovaskuläre Ereignisrate hin. Die DAN kann bei Erwachsenen mittels spezieller Teste geprüft werden, die die Herzfrequenzänderung und das Blutdruckverhalten untersuchen, wenn Provokationsverfahren zum Beispiel mit Valsalva-Manöver, tiefer Atmung und Stehversuch durchgeführt werden. Die Teste weisen aber eine geringe Sensitivität auf. Die Herzfrequenzvaviabilität (HRV) selbst ist aber ein gutes Verfahren, um eine autonome Dysregulation aufzudecken. Ziel: Prüfung des autonomen Nervensystems bei Kindern mit Diabetes mellitus in Abhängigkeit von der Dauer und Schwere der gestörten Glucosestoffwechselsituation. Patienten und Methoden: Bei 50 Patienten mit insulinpfichtigem Diabetes mellitus und 30 gesunden Kindern wurde die HRV geprüft. Ergebnisse: Patienten mit einer Diabetesdauer über 8 Jahre zeigten eine signifikante Störung des autonomen Nervensystems mit Reduktion der HRV. War die Dauer des Diabetes weniger als 8 Jahre, war nur der Parameter pNN 50 erniedrigt. Eine gestörte HRV wurde nur bei Patienten mit geströter metabolischer Situation gefunden. Bei Patienten mit einem HbA1C Wert > 8% fanden sich erniedrigte Werte für r-MSSD, pNN50 und das Gesamtpowerspektrum im Vergleich zu Kontrollpersonen. Patienten mit HbA1C-Werten unter 8% blieben demgegenüber unauffällig. Schlussfolgerung: Die HRV-Analyse bei insulinplfichtigen Kindern mit Diabetes mellitus kann genutzt werden, um im subklinischen Bereich eine Störung der autonomen Funktion des Nervensystems zu überprüfen. Im Wesentlichen liegt eine Parasymathikusstörung vor. Die autonome Dysregulation ist korreliert zur Dauer und zum metabolischen Status der Kinder.

Electrical and autonomic cardiac function in patients with Dravet syndrome

Dravet syndrome (DS) is an epileptic encephalopathy related mainly to mutations in the SCN1A gene, encoding for neuronal sodium channels. Patients with DS have a high risk of sudden unexpected death in epilepsy (SUDEP). In this study we investigated whether patients with DS present abnormalities in electrical and autonomic cardiac function. To this aim we assessed ventricular repolarization and heart rate variability (HRV) on standard electrocardiography (ECG) and on 24‐h ECG Holter monitoring, respectively, in 20 patients affected by DS (6.8 ± 4 years, 11 female). As age‐ and sex‐matched control groups, we also studied 20 patients with other epileptic syndromes receiving antiepileptic drugs (ES/AED, 6.0 ± 5 years, 12 female), 20 patients with other epileptic syndromes without treatment (ES/no‐AED, 6.7 ± 4 years, 10 female), and 20 healthy children (HC, 7.2 ± 5 years, 11 females). Data analysis showed that patients with DS had depressed HRV variables compared to both ES patients (ES/AED and ES/no‐AED) and HC control group, whereas no significant differences in HRV variables were found between ES patients (with and without treatment) and HC. There was no significant difference between patients with DS and all the other control groups in RR intervals, QT, and QTc interval analysis. In conclusion, DS patients display an imbalance of cardiac autonomic function toward a relative predominance of adrenergic tone compared to both healthy children and patients with other forms of epilepsy, independent of antiepileptic therapy. Follow‐up studies should clarify the clinical significance of this autonomic impairment and whether HRV analysis can be helpful in predicting the risk of sudden death in patients with DS.

Effects of prophylactic ibuprofen on cerebral and renal hemodynamics in very preterm neonates

To evaluate the effects on cerebral and renal blood flow velocities of ibuprofen when used as prophylaxis for patent ductus arteriosus in preterm neonates (gestational age ≤30 weeks).

Systematic review and meta‐analysis of currently available clinical evidence on migraine and patent foramen ovale percutaneous closure: Much ado about nothing?

Objectives: To investigate the role of transcatheter closure of patent foramen ovale on the occurrence of migraine. Background: In recent years, a potential relationship between, migraine, stroke, and patent foramen ovale (PFO) has emerged. Methods: BioMedCentral, Google Scholar, and PubMed from January 2000 to December 2008 were systematically searched for pertinent clinical studies. Secondary sources were also used. Secondary prevention studies of transcatheter closure for patent foramen ovale were required to include at least more than 10 patients followed for more than 6 months. The primary end‐point was the rate of cured or significantly improved migraine after percutaneous PFO closure. Results: After excluding 637 citations, we finally included a total of 11 studies for a total of 1,306 patients. Forty percent of the subjects included suffered from migraine, while most had a previous history of transient ischemic attack/stroke and were investigated retrospectively. Quantitative synthesis showed that complete cure of migraine in 46% (95% C.I.25–67%), while resolution or significant improvement of migraine occurred in 83% (95% C.I. 78–88%) of cases. Conclusions: Notwithstanding the limitations inherent in the primary studies, this systematic review suggests that a significant group of subjects with migraine, in particular if treated after a neurological event, may benefit from percutaneous closure of their patent foramen ovale. However, many questions remain unsolved.

Incomplete Kawasaki syndrome followed by systemic onset-juvenile idiopathic arthritis mimicking Kawasaki syndrome.

A 3-month-old child was first treated for incomplete Kawasaki syndrome with three cycles of intravenous immunoglobulins and aspirin, then with methylprednisolone which led to fever remission. The same child was re-hospitalized after a 10-month-period of well-being for the suspicion of a new episode of Kawasaki syndrome, which appeared to be immunoglobulin-resistant: extensive testing failed to provide an alternative diagnosis of any infectious or infiltrative disease. Diagnosis of systemic onset-juvenile idiopathic arthritis was postulated upon the long persistence of fever and inflammatory signs, which subsided only after starting corticosteroid treatment.

Endothelial and Platelet Function in Children With Previous Kawasaki Disease

We investigated whether children with a previous Kawasaki disease (KD) have evidence of abnormal vascular and/or platelet function. We included 14 patients with previous KD and 14 matched controls. We assessed endothelial function by flow-mediated dilation (FMD), carotid intima–media thickness (cIMT), coronary microvascular function by coronary blood flow response (CBFR) to cold pressor test, and platelet reactivity by measuring monocyte–platelet aggregates (MPAs) and CD41-platelet expression by flow cytometry. No differences were found between the groups in FMD, cIMT, or CBFR to cold pressor test. The MPAs were similar in patients with KD and controls. CD41-platelet expression, however, was significantly increased in patients with KD compared with controls, both at rest (14.3 ± 1.9 vs 12.4 ± 1.9 mean fluorescence intensity [mfi], P = .01) and after adenosine diphosphate stimulation (19.3 ± 1.3 vs 17 ± 1.7 mfi, P < .001). In conclusion, children with a previous episode of KD showed increased platelet activation, compared with healthy participants despite no apparent vascular abnormality at follow-up.

Kawasaki syndrome and concurrent Coxsackie virus B3 infection

We describe two previously healthy children who were hospitalized in the same period in different departments of our University with clinical signs of Kawasaki syndrome, which were treated with intravenous immunoglobulins and acetylsalicylic acid: in both cases, Coxsackie virus infection was concurrently demonstrated by enzyme-linked immunosorbent assay, and complement fixation test identified antibodies to serotype B3. In the acute phase, both patients presented hyperechogenic coronary arteries, but no cardiologic sequels in the mid term. The etiological relationship between Kawasaki syndrome and Coxsackie viruses is only hypothetical; however, the eventual identification of ad hoc environmental triggers is advisable in front of children with Kawasaki syndrome, with the aim of optimizing epidemiological surveillance and understanding the intimate biological events of this condition.