Implantation of a novel insertable cardiac monitor: preliminary multicenter experience in Europe.

BACKGROUND: The LUX-Dx™ is a novel insertable cardiac monitor (ICM) introduced into the European market since October 2022. PURPOSE: The aim of this investigation was to provide a comprehensive description of the ICM implantation experience in Europe during its initial year of commercial use. METHODS: The system comprises an incision tool and a single-piece insertion tool pre-loaded with the small ICM. The implantation procedure involves incision, creation of a device pocket, insertion of the ICM, verification of sensing, and incision closure. Patients receive a mobile device with a preloaded App, connecting to their ICM and transmitting data to the management system. Data collected at European centers were analyzed at the time of implantation and before patient discharge. RESULTS: A total of 368 implantation procedures were conducted across 23 centers. Syncope (235, 64%) and cryptogenic stroke (34, 9%) were the most frequent indications for ICM. Most procedures (338, 92%) were performed in electrophysiology laboratories. All ICMs were successfully implanted in the left parasternal region, oriented at 45° in 323 (88%) patients. Repositioning was necessary after sensing verification in 9 (2%) patients. No procedural complications were reported, with a median time from skin incision to suture of 4 min (25th-75th percentiles 2-7). At implantation, the mean R-wave amplitude was 0.39 ± 0.30 mV and the P-wave visibility was 91 ± 20%. Sensing parameters remained stable until pre-discharge and were not influenced by patient characteristics or indications. Procedural times were fast, exhibited consistency across patient groups, and improved after an initial experience with the system. Operator Operator feedback on the system was positive. Patients reported very good ease of use of the App and low levels of discomfort after implantation. CONCLUSIONS: LUX-Dx™ implantation appears efficient and straightforward, with favorable post-implantation sensing values and associated with positive feedback from operators and patients.

Sports Eligibility After Risk Assessment and Treatment in Children with Asymptomatic Ventricular Pre-excitation.

BACKGROUND AND OBJECTIVE: Many studies concern the management of young patients with symptomatic Wolff-Parkinson-White (WPW) syndrome, but little information exists on the significance and prognosis of ventricular pre-excitation (VPE) in asymptomatic children. The aim of the study was to evaluate the risk of sudden death in young athletes with asymptomatic VPE by transesophageal electrophysiological study (TEEPS) and their sports eligibility after the risk assessment and/or ablative treatment. METHODS: Ninety-one asymptomatic children and adolescents underwent TEEPS both at rest and during adrenergic stress (exercise testing or isoproterenol infusion). After electrophysiological testing, patients were assessed in the 36 months of follow-up. RESULTS: Thirty-three patients (36.3 %) had a benign form of VPE and were allowed to participate in competitions. Ten patients (11 %) were at borderline risk; thus, sport eligibility was evaluated individually. Forty-eight patients (52.7 %) showed inducible sustained atrioventricular reentrant tachycardia and/or atrial fibrillation (AF), 11 of whom (12.1 % of total population) had a potential risk of sudden cardiac death due to AF inducibility during physical stress. Forty-five young athletes underwent transcatheter ablation (TCA). TCA was interrupted in 12 patients (26.7 %) because of the high procedural risk linked to septal accessory pathway (AP) location. There were no TCA-related complications, and all patients remained asymptomatic during follow-up. CONCLUSION: Most of the young athletes with asymptomatic VPE may be allowed to participate in competitive sports after an adequate risk assessment and/or ablative treatment. However, in our opinion, special care should be taken to avoid procedural complications, which are unacceptable in asymptomatic patients.

Pacemaker and implantable cardioverter defibrillator implantation in pediatric patients.

Pediatric pacing presents peculiar challenges and characteristics due to the peculiarity of children and adolescents, above all the somatic growth, but also the active lifestyle, the susceptibility to infections, and the generally anticipated long survival. In contrast, pacemaker (PM) generator and leads are designed for adult patients. Studies concerning children with PM are usually small, disomogeneous and without control groups. Large studies are rare. Moreover, concerns have been raised about long-term outcome of leads, ventricular and valvular dysfunction, venous patency, cosmetic results and psychological factors. So, it is still debated which systems have to be preferred, between the endocardial and the epicardial with steroid-eluting leads. Pediatric PM and (ICDs) show good results, but complications are still frequent, generally lead related, and often require reinterventions. As a general rule, less leads are implanted in children, less complications will occur in the future, and the simplest pacing system (generally, single-chamber PM) has better outcome. The creation of an atrial loop might allow the ''elongation'' of the lead with the growth. Endocardial and epicardial pacing with steroid-eluting leads have comparable electrical performances, expecially in absence of other congenital heart defects and previous heart surgery, although endocardial pacing shows the best outcomes: it should be the first choice in children over 10-15 kg.

Causes of cross-over in unilateral neglect: between-group comparisons, within-patient dissociations and eye movements.

Patients with left unilateral neglect bisect long horizontal lines to the right of the true centre. However, when given short lines, many of the same patients mark the midpoint to the left of the true centre, towards the otherwise neglected space. This paradoxical phenomenon has been termed 'cross-over' and is difficult to explain based on current accounts of the neglect syndrome. To explore the causes of cross-over, in a first study we evaluated bisection of 20, 100 and 200 mm horizontal lines in groups of unilateral brain-damaged patients with neglect and hemianopia, with neglect and no hemianopia, with hemianopia and no neglect and without neglect or hemianopia. Cross-over of 20 mm lines was found only in neglect patients with hemianopia. To ascertain further the influence of visual field defects on cross-over, in a second study we compared the performance of two right-brain-damaged patients with contralesional neglect and inferior quadrantanopia with that of a patient with inferior quadrantanopia and no neglect. Patients bisected lines oriented so as to cross or uncross the blind quadrant of the visual field. When short 20 mm lines crossed the blind quadrant, neglect patients showed cross-over; when the same lines crossed the seeing quadrants cross-over was absent. These findings were confirmed by the examination of a neglect patient with sparing of the central 5 degrees of the contralesional left visual hemifield in the right eye and no sparing in the left eye. In monocular viewing, cross-over was present when 20 mm lines were bisected with the left eye and absent when bisected with the right eye. Recording of eye movements showed that at the moment of bisection left eye fixations shifted towards the contralesional line endpoint whereas right eye fixations remained anchored to the centre of the line. With long lines, both eyes deviated ipsilesionally. These results show that in neglect patients ipsilesional deviation in the bisection of long lines turns into apparently paradoxical contralesional bisection of short ones only when these cross a retinotopically blind sector of the neglected space. Cross-over seems to depend on the small spatial effects produced by reflexive contralesional gaze shifts allowing eccentric fixations with the seeing hemifield. During the bisection of long lines, these effects are cancelled out by the strong attentional deviation induced by the marked extension of the ipsilesional line segment. This explanation establishes coherence between cross-over and current accounts of the neglect syndrome.

Paroxysmal atrioventricular block in young patients.

We describe 17 patients (8 girls, and 9 boys), aged 9.6 +/- 5.7 years, with paroxysmal atrioventricular block (PAVB), a condition rarely described in children. Holter monitoring documented the PAVB in 15 patients, and tilt test was performed in 4 patients (positive in 1). The electrocardiograph (ECG) was normal in 7 patients. Two patients had acquired and 11 patients had congenital heart disease (CHD). Syncope or presyncope were present in 7 patients. A normal ECG was significantly more frequent in symptomatic patients. Pauses were significantly longer in girls and in children <5 years. PAVB was recorded only during nocturnal hours in 6 patients and throughout the day in the others. The sinus rate decreased during PAVB in 6 patients and increased in 4 (generally younger girls with symptoms). Permanent pacemakers were implanted in 13 patients, including 7 asymptomatic patients with CHD and severe bradycardia. During follow-up (3.7 +/- 2.5 years), 1 patient developed complete AVB. Although PAVB was still present in 91% of paced patients, symptoms did not recur because pacing prevented the pauses. In conclusion, PAVB is a rare arrhythmia. Autonomic nervous system dysfunction seems to play an etiological role and permanent pacing was an effective treatment.

Does chronic pacing affect exercise capacity after Mustard operation for transposition of the great arteries?

Late survival after Mustard repair of transposition of the great arteries is generally good but is often characterized by progressive deterioration of ventricular function and by late postsurgical arrhythmias, thus imposing the need for permanent pacing. To evaluate how chronic pacing affects long-term exercise capacity, we compared two groups of these patients: group 1, comprising 12 patients, aged 9.0 +/- 2.6 years, without pacemaker; and group 2, comprising 18 patients, aged 9.3 +/- 2.0 years, with pacemaker. Patient evaluation included history, physical examination electrocardiograph, Holter monitoring, and echocardiography. Pacing modes were as follows: AAI (6 patients), AAIR (9 patients), VVI (2 patients), and VVIR (1 patient). At exercise test we evaluated exercise tolerance, maximum heart rate, blood pressure, oxygen consumption, and cardiac output at rest and at peak exercise. The two groups were comparable for all variables examinated. All pacemakers showed normal function. During the exercise, 11 of 12 patients in group 1 showed sinus rhythm, and in group 2, 11 patients showed sinus rhythm, 5 junctional rhythm, and 2 continuous pacing. There were no significant differences between groups. Chronically paced Mustard patients but with restoration of spontaneous rhythm during the exercise test do not show reduced exercise tolerance in comparison with nonpaced Mustard patients.

Heart rate variability in healthy children and adolescents is partially related to age and gender.

We evaluated 24-h time-domain heart rate variability (HRV) in 103 (46 females) healthy children and adolescents. Subjects were divided into four male and four female groups (ages 1-5, 6-10, 11-15, 16-20 years) and 24-h ambulatory Holter monitoring was performed. HRV was assessed by SDNN, SDNN index (SDNN-i), SDANN, rMSSD, pNN50. Males showed SDNN and SDANN values significantly higher than females while for SDNN-i, rMSSD, pNN50 there were no significant differences between sexes. With increasing age, there is a progressive and significant decrease of HR and increase of SDANN. On the other hand, SDNN, SDNNi, pNN50 and rMSSD increased significantly only between the first two age-groups. rMSSD and pNN50 were significantly related to body mass index. Thus, SDNN and SDANN, overall HRV measures, increased with age and were gender-related. HRV indices of parasympathetic function (rMSSD, pNN50) and SDNN-i increased up to 10 years of age and were gender-unrelated. These data demonstrate that in healthy children and adolescents there is a progressive modification of HRV that may reflect a progressive evolution of the autonomic nervous system, with different pattern measure-dependent. This paper enables us to compare, in future works, HRV in pediatric subjects in different groups according to the different HRV measures under examination.

Permanent junctional reciprocating tachycardia in infants and children: effectiveness of medical and non-medical treatment.

BACKGROUND: The aim of this study was to identify, in children affected by permanent junctional reciprocating tachycardia (PJRT), the effective treatment. METHODS: Seventeen children (9 males, 8 females, mean age 59 +/- 62 months, median 24) affected by PJRT were referred to our Institute between the years 1987 and 2000. RESULTS: Pharmacological therapy was successfully used in 14 patients: flecainide and propranolol in 5 of them, amiodarone alone in 5 and associated with propranolol in 2, propafenone alone in 1 and in association with sotalol in 1. These drugs were given for a mean period of 54.5 +/- 49.8 months with resolution of the cardiomyopathy in 7/7 patients. Treatment had been continued for 3-6 months and there were no side effects. Nine patients were treated with radiofrequency transcatheter ablation, after 78 +/- 53.5 months of medical treatment, at a mean age of 150 +/- 16 months. The shortest endocardial ventriculo-atrial (VA) interval during tachycardia was recorded in all cases at the coronary sinus ostium (mean value of local VA-surface RP' interval -38 ms, range -24/-55 ms). Successful ablation of the anomalous pathway was obtained at this site in all patients (mean watts delivered 26 +/- 3 W, mean T degrees 64 +/- 5 degrees C). During the follow-up period (mean 21 +/- 17 months) 2 patients with recurrences of PJRT underwent a second successful procedure. CONCLUSIONS: PJRT in pediatric patients can be successfully treated with antiarrhythmic drugs, this may allow delay of the highly effective radiofrequency ablation treatment until the children have reached an adequate growth.

Amiodarone-induced torsade de pointes in a child with dilated cardiomyopathy.

Amiodarone has a high incidence of side effects, but few pro-arrhythmic effects. We report a case of amiodarone-induced torsade de pointes in a child aged 10 years. The patient had severe dilated cardiomyopathy, and even though he was treated with low oral doses of amiodarone, without dosage increments and electrolyte imbalance, he developed torsade de pointes at nights, after T-wave modification and increases of the corrected QT interval (QTc, 20%), QT dispersion (QTd, 175%) and QTcd (116%). The arrhythmic events were preceded by sinus bradycardia at Holter monitoring. Amiodarone therapy was discontinued. Intravenous magnesium administration was not effective in the suppression of torsade de pointes. High-rate atrial pacing prevented recurrences of the arrhythmias and reduced the QTc interval by 20%, QTd by 50%, and QTcd by 70%; QTd and QTcd returned below normal limits. This case underscores the need of careful electrocardiographic monitoring during amiodarone therapy.

[The heart of anorexic adolescents]. / Il cuore nelle adolescenti anoressiche.

BACKGROUND: Anorexia nervosa (AN) is often associated with cardiac changes, such as thinning of the left ventricle (LV), reduction of LV mass, abnormalities of mitral valve function and systolic dysfunction. Some authors have reported QT interval prolongation and sudden death in these patients. METHODS: We studied 23 adolescent females, aged 14.7 +/- 2 years (mean +/- SD), with AN. Serum electrolytes, proteins and albumin were measured in all patients. Electrocardiogram, Doppler-echocardiogram and chest X-rays were also performed on the same day. Eighteen patients were also examined via indirect calorimetry (difference from basal metabolic rate) and 21 underwent dosage of thyroid hormones. RESULTS: The patients, who were of normal height (159 +/- 7.4 cm), were underweight (36 +/- 4.8 kg) and had a body mass index (BMI) of less than 19 (14.2 +/- 1.3). Serum electrolytes, proteins, albumin and chest X-rays were substantially normal in all patients; 74% of them showed reduction of FT3. The calorimetry was reduced (-27.1 +/- 10.6%) with the exception of one patient. Resting heart rate was 58 +/- 12 bpm. We found normal values for PR, QRS, QT (0.41 +/- 0.03 s1/2) and QTc intervals (0.40 +/- 0.03 s1/2) and QT dispersion (40.9 +/- 14.1 ms). Echocardiography showed a reduction in the dimensions of the interventricular septum (52% of patients), LV free wall (61%), left atrium (31%) and LV mass (61%). Fractional shortening was normal in all but one patient. In 61% of cases, there was mild or moderate pericardial effusion that was clinically silent and inversely related to BMI (r = -0.38, p 0.08, ns), to calorimetry (r = -0.56, p < 0.0055), to FT3 (r = -0.53, p < 0.05) and to sodium concentration (r = -0.43, p 0.04). CONCLUSIONS: Teen-agers with AN often show a reduction in LV thickness and mass, as well as clinically silent pericardial effusion that is inversely related to BMI, calorimetry, FT3 and sodium serum concentrations. We did not find any prolongation of QTc interval or of QT dispersion.

Genetic history of cystic fibrosis mutations in Italy. I. Regional distribution.

Earlier analysis of the Italian population showed patterns of genetic differentiation that were interpreted as being the result of population settlements going back to pre-Roman times. DNA disease mutations may be a powerful tool in further testing this hypothesis since the analysis of diseased individuals can detect variants too rare to be resolved in normal individuals. We present data on the relative frequencies of 60 cystic fibrosis (CF) mutations in Italy and the geographical distribution of the 12 most frequent CF mutations screened in 3492 CF chromosomes originating in 13 Italian regions. The 12 most frequent mutations characterize about 73% of the Italian CF chromosomes. The most common mutation, delta F508, has an average frequency of 51%, followed by N1303K and G542X, both with average frequencies around 5%. Multivariate analyses show that the relative frequencies of CF mutations are heterogeneous among Italian regions, and that this heterogeneity is weakly correlated with the geographical pattern of non-DNA 'classical' genetic markers. The northern regions are well differentiated from the central-southern regions and within the former group the western and eastern regions are remarkably distinct. Moreover, Sardinia shows the presence of mutation T338I, which seems absent in any other European CF chromosome. The north-western regions of Italy, characterized by the mutation 1717-1G-->A, were under Celtic influence, while the north-east regions, characterized by the mutations R1162X, 2183AA-->G and 711 + 5G-->A, were under the influence of the Venetic culture.

Permanent overdrive atrial pacing in the chronic management of recurrent postoperative atrial reentrant tachycardia in patients with complex congenital heart disease.

This study investigated the value of permanent atrial pacing as an adjunct to the current therapy in the chronic management of recurrent postoperative atrial reentrant tachycardia in patients with complex congenital heart disease. We studied the postpacing clinical course in 18 patients with recurrent atrial reentrant tachycardias unresponsive to conventional therapy who had an implanted atrial pacemaker. The pacemaker was programmed at a lower pacing rate 20% faster than the spontaneous mean daily rate previously determined with 24-hour Holter monitoring. Serial Holter recordings and pacemaker programming sessions were subsequently performed trying to maintain a paced atrial rhythm overdriving the spontaneous rhythm as long as possible. Twenty-four hour Holter monitoring documented a prevalent (> 80%) paced rhythm during the daily hours in all patients during the follow-up; all patients, however, required at least once a variation in programmed mode and pacing rate. Antiarrhythmic medications were discontinued after 6 months if the patient remained arrhythmia free while on pacing. Recurrences of atrial reentrant tachycardia occurred in five patients (29%) during the initial 6 months interval after the pacemaker implantation, while late recurrences occurred in only two patients (11%). One patient died suddenly 10 months after the pacemaker implant. At the end of the follow-up, 15 patients (83%) were arrhythmia-free and only 2 of them were still on antiarrhythmic drugs. We conclude that permanent atrial overdrive pacing can be an important tool in the management of patients with atrial reentrant tachycardia following repair of congenital heart disease.

A specific cystic fibrosis mutation (T3381) associated with the phenotype of isolated hypotonic dehydration.

We carried out molecular screening for mutations in the cystic fibrosis transmembrane regulator (CFTR) gene in eight children of Sardinian descent seen because of hypotonic dehydration associated with hyponatremia, hypochloremia, hypokalemia, and metabolic alkalosis; none had pulmonary or pancreatic involvement. All the patients had the T3381 mutation either in homozygosity or compound heterozygosity with another CF mutation. The T3381 mutation was not detected in patients with CF who had classic symptoms or in healthy persons of the same descent. These data suggest that the T3381 mutation is associated with a specific mild CF phenotype.

The distribution of DR4 haplotypes in Sardinia suggests a primary association of type I diabetes with DRB1 and DQB1 loci.

The contribution of genetic variation at HLA class II loci to the susceptibility to and protection from IDDM was investigated by analyzing the distribution of HLA-DRB1*04 haplotypes in 630 Sardinian newborns and 155 Sardinian IDDM patients. The different RRs and ARs of the various DR4-DQB1*0302 haplotypes, significantly ranging from the strongly associated DRB1*0405, DQB1*0302 to the protective DRB1*0403, DQB1*0302 haplotypes, provides clearcut evidence that the DRB1 locus is crucial in conferring IDDM predisposition or protection. Also, the DQB1 locus influences IDDM predisposition or protection by restricting the disease-positive association to DRB1*0405 haplotypes carrying the susceptibility DQB1*0302 or DQB1*0201 alleles but not the protective DQB1*0301 allele. Haplotype analysis not only suggests that the DRB1 and DQB1 loci influence IDDM risk in the same way, but also that the HLA-linked protection is "dominant" compared with "susceptibility." These results, obtained from a population with one of the highest IDDM incidences in the world, define more clearly the contribution of the various HLA loci to IDDM protection or susceptibility and allow a more precise calculation of AR.

Combinations of specific DRB1, DQA1, DQB1 haplotypes are associated with insulin-dependent diabetes mellitus in Sardinia.

The Sardinian population has an extremely high incidence of IDDM (30.2 of 100.000 in the age group of 0-14 years). This study reports the molecular characterization of HLA class II genes in 120 IDDM sporadic patients and 89 healthy subjects of Sardinian origin. Compared with other Caucasians, both Sardinian patients and controls had an unusual distribution of haplotypes and genotypes. In particular, there was a high gene frequency of the DRB1*0301, DQA1*0501, DQB1*0201 susceptibility haplotype both in patients (0.58) and controls (0.23) while a reduction of the DRB1*1501, DQA1*0102, DQB1*0602 protective haplotype (0.03) was observed in the healthy population. This distribution may partially explain the high incidence of IDDM reported in Sardinia. The analysis of the DQ beta 57 and DQ alpha 52 residues showed that the absence of Asp 57 and the presence of Arg 52 were associated with IDDM in a dose-response manner. On the other hand, we found that (a) a very similar distribution of these residues was found when comparing Sardinians with another healthy Caucasian population from the same latitude but with a lower rate of IDDM incidence; (b) several genotypes encoding the identical DQ alpha 52/DQ beta 57 phenotype carried very different relative risks; and (c) the DRB1*0403, DQA1*0301, DQB1*0304 haplotype (DQ beta 57 Asp-neg and DQ alpha 52 Arg-pos) was found in 40% of the DR4-positive controls but not in patients (p = 0.00034), while the DRB1*0405, DQA1*0301, and DQB1*0302 haplotype carrying the same residues at the same positions was found in 70% of the DR4-positive patients and in only one control (p = 0.00003). These findings suggest that IDDM susceptibility cannot be completely explained by the model in which only DQ alpha 52 and DQ beta 57 residues are taken into account.

Molecular bases for cystic fibrosis in the Sardinian population.

Cystic fibrosis (CF) is a relatively uncommon genetic disorder in the Sardinian population. In this study, we have defined the frequency of the most common CF mutation (delta F508) and carried out a genotype-phenotype correlation analysis in a group of 21 patients with CF and of Sardinian descent. We detected the delta F508 mutation in 24 (57%) out of the 42 CF chromosome investigated. This mutation was found in the homozygous state in 9 patients and in the heterozygous state in 6 patients. The remaining 6 patients had other mutations. The delta F508 mutation was associated only with the KM19/XV2c 2 1 haplotype. Genotype-phenotype correlation analysis did not give clear-cut results, probably because of the small number of patients investigated. However, out of the four patients with meconium ileus, three were homozygous and one was heterozygous for the delta F508 mutation, confirming that the presence of delta F508 or other severe mutations in the homozygous state is the prerequisite for the development of meconium ileus.

Present-day G-6-PD deficit in Sardinia with respect to malarial morbidity and mortality in the past.

Current Gd- gene distribution in Sardinia is analyzed using data on a sample of 4300 Sardinian males examined at the time of their pre-military checkup from 1983 to 1986, as well as data in the literature. Also examined is the relationship of current G-6-PD deficit distribution to probable malarial morbidity and mortality during the first half of this century. From data on deficit distribution by altitude analyzed for 100 villages of the island, the authors suggest the possibility of using altitude above sea level to replace incidence of malaria, which was used in the past only as an indicative, rather than substitutive, parameter. The authors also corroborate the hypothesis that G-6-PD deficit distribution is basically a consequence of selection caused by malarial endemicity, although several other factors may have interacted to influence Gd- gene incidence and distribution.