The burden of radiation exposure in congenital heart disease: the Italian cohort profile and bioresource collection in HARMONIC project.

BACKGROUND: The European-funded Health Effects of Cardiac Fluoroscopy and Modern Radiotherapy in Pediatrics (HARMONIC) project aims to improve knowledge on the effects of medical exposure to ionizing radiation (IR) received during childhood. One of its objectives is to build a consolidated European cohort of pediatric patients who have undergone cardiac catheterization (Cath) procedures, with the goal of enhancing the assessment of long-term radiation-associated cancer risk. The purpose of our study is to provide a detailed description of the Italian cohort contributing to the HARMONIC project, including an analysis of cumulative IR exposure, reduction trend over the years and an overview of the prospective collection of biological samples for research in this vulnerable population. METHODS: In a single-center retrospective cohort study, a total of 584 patients (323 males) with a median age of 6 (2-13) years, referred at the Pediatric Cardiology in Niguarda Hospital from January 2015 to October 2023, were included. Biological specimens from a subset of 60 patients were prospectively collected for biobanking at baseline, immediately post-procedure and after 12 months. RESULTS: Two hundred fifty-nine (44%) patients were under 1 year old at their first procedure. The median KAP/weight was 0.09 Gy·cm2/kg (IQR: 0.03-0.20), and the median fluoroscopy time was 8.10 min (IQR: 4.00-16.25). KAP/weight ratio showed a positive correlation with the fluoroscopy time (Spearman's rho = 0.679, p < 0.001). Significant dose reduction was observed either after implementation of an upgraded technology system and a radiation training among staff. The Italian cohort includes 1858 different types of specimens for Harmonic biobank, including blood, plasma, serum, clot, cell pellet/lymphocytes, saliva. CONCLUSIONS: In the Italian Harmonic cohort, radiation dose in cardiac catheterization varies by age and procedure type. An institution's radiological protection strategy has contributed to a reduction in radiation dose over time. Biological samples provide a valuable resource for future research, offering an opportunity to identify potential early biomarkers for health surveillance and personalized risk assessment.

Ventricular Septal Defect and Right-Sided Infective Endocarditis.

Right-sided infective endocarditis (IE), which represents a small but not negligible percentage of IE cases, can be observed in patients with congenital heart diseases. We discuss the case of a young woman with unrepaired perimembranous ventricular septal defect and repeated episodes of right ventricle and tricuspid valve IE with septic embolism.

Cor Triatriatum Dexter: Contrast Echocardiography Is Key to the Diagnosis of a Rare but Treatable Cause of Neonatal Persistent Cyanosis.

Cor triatriatum dexter (CTD) is an extremely uncommon and underreported congenital cardiac anomaly in which the persistence of the embryonic right venous valve separates the right atrium into two chambers with varying degrees of obstruction to antegrade flow and variable degree of right to left shunt at atrial level. Depending on the size of the valves, clinical manifestations vary from absence of symptoms to severe hypoxia, requiring urgent surgical correction. We herein describe the diagnostic difficulties in a case of neonatal CTD, who developed increasingly severe and unresponsive cyanosis, first interpreted as postnatal maladjustment with pulmonary hypertension. The failure to respond to oxygen and pulmonary vasodilators led us to reconsider a different diagnosis. The use of contrast echocardiography improved the diagnostic performance of transthoracic echocardiogram (TTE) and revealed a massive right-to-left shunt secondary to the presence of an atrial membrane that required urgent surgery.

Bathing epilepsy: a video case report.

Bathing epilepsy is a rare form of reflex epilepsy triggered by bathing in room temperature water. It predominates in boys with a mean age of 15 months and its evolution is benign. Diagnosis of bathing epilepsy requires the exclusion of other paroxysmal disorders triggered by water contact. Video-EEG confirmation of the seizures is necessary to reach a diagnosis of certainty and to allow adequate management. We present the case of a one-year-old boy who experienced recurrent episodes of unresponsiveness and cyanosis while bathing in lukewarm water. The diagnosis of bathing epilepsy was confirmed by the video-EEG recording of a seizure, showing left-sided frontotemporal delta activity with rapid contralateral spread. Therapy with levetiracetam was effective, subsequently allowing bathing without further seizures.

Microfluidics for nanomedicines manufacturing: An affordable and low-cost 3D printing approach.

During the last decade, an innovative lab on a chip technology known as microfluidics became popular in the pharmaceutical field to produce nanomedicines in a scalable way. Nevertheless, the predominant barriers for new microfluidics users are access to expensive equipment and device fabrication expertise. 3D printing technology promises to be an enabling new field that helps to overcome these drawbacks expanding the realm of microfluidics. Among 3D printing techniques, fused deposition modeling allows the production of devices with relatively inexpensive materials and printers. In this work, we developed two different microfluidic chips designed to obtain a passive micromixing by a "zigzag" bas-relief and by the presence of "split and recombine" channels. Computational fluid dynamics studies improved the evaluation of the mixing potential. A fused deposition modeling 3D printer was used to print the developed devices with polypropylene as manufacturing material. Then, two different model nanocarriers (i.e., polymeric nanoparticles and liposomes), loading cannabidiol as model drug, were formulated evaluating the influence of manufacturing parameters on the final nanocarrier characteristics with a design of experiments approach (2-level full factorial design). Both the chips showed an effective production of nanocarriers with tunable characteristics and with an efficient drug loading. These polypropylene-based microfluidic chips could represent an affordable and low-cost alternative to common microfluidic devices for the effective manufacturing of nanomedicines (both polymer- and lipid-based) after appropriate tuning of manufacturing parameters.

Efficacy of Diving Reflex in Near-Term Fetal Tachycardia.

BACKGROUND: Sustained fetal supraventricular tachycardia is a potentially life-threatening disorder and is usually treated by administering antiarrhythmia drugs to the mother, which can require at least 48-72 hours to achieve normal sinus rhythm. In neonates with supraventricular tachycardia, first-line treatment is stimulation of the vagus nerve to elicit the diving reflex, commonly by application of a cold pack to the face, with a high, albeit sometimes temporary, success rate. CASE: We describe a case of fetal supraventricular tachycardia at term treated successfully by eliciting the diving reflex with an ice pack to the maternal abdomen over the lower uterine segment. The neonate was given propranolol augmented with flecainide because of recurrent supraventricular tachycardia. He remained in a stable sinus rhythm without side effects 5 months later. CONCLUSIONS: Cardioversion of fetal supraventricular tachycardia at term by eliciting the diving reflex could be offered to allow normal labor and vaginal delivery.

Feasibility and safety of transcatheter closure of atrial septal defects with deficient posterior rim.

OBJECTIVES: To evaluate the feasibility and safety of percutaneous closure of complex secundum-type atrial septal defects (ASD) in patients with posterior-inferior rim deficiency. BACKGROUND: Transcatheter approach is the method of choice for ASD closure; however, up to now 20% of the defects are not considered suitable for percutaneous intervention because of the lack of surrounding rims, especially the posterior-inferior. METHODS: A total of 268 patients were evaluated between March 2005 and April 2011 for ASD closure. Twenty-four patients (9%) were not considered suitable for a percutaneous intervention and referred to surgery due to inadequate rims or a large defect diameter. Out of the remaining 244 patients, 25 (10,2%) had posterior-inferior rim deficiency and represent our study group. RESULTS: After failure of the conventional approach, alternative techniques were attempted. In 16 patients, an adjusted deployment and alignment maneuver approach was successful. In 5 other patients, a slide out technique was successfully performed by exploiting the right upper pulmonary vein. Finally in the remaining 4 patients, ASD closure was obtained by completely re-orienting the system with a jugular approach. No peri-procedural complications occurred, and at 12-month transesophageal echocardiography evaluation no residual shunt could be detected. CONCLUSIONS: Our data show the feasibility of percutaneous approach for ASD closure in presence of a deficient posterior-inferior rim. The procedural success is strictly related to correct sizing and demonstration of a balloon notch on fluoroscopy. Long-term follow-up supports efficacy of the procedure in these selected cases.

Evaluation of the efficacy of an hyaluronic acid-based biogel on periodontal clinical parameters. A randomized-controlled clinical pilot study.

UNLABELLED: Hyaluronic acid (HA) is an ubiquitous form of non-sulphated glycosaminoglycan of the extracellular matrix of all mammalian connective tissues. It is mainly present during tissue's formation or during most of initial tissue's repair processess. Cell migration, adhesion and differentiation are only part of several unique biological characteristics of HA which have been under investigation in the past decades. AIM OF THE STUDY: Evaluate the possible positive effect of an esterified form of HA on gingival tissues in mild chronic periodontitis patients, seeking for the reduction of all the periodontal disease clinical parameters PLI (Plaque Index), BOP (Bleeding on Probing), PPD (Probing Pocket Depth), GI (Gingival Index), PAL (Probing Attachment Level). MATERIALS AND METHODS: The study is an open, intra-patient, controlled, single center pilot clinical trial including 19 adult patients with mild chronic periodontitis and shallow pockets (< 4 mm) in at least two different quadrants. One quadrant was treated with HA gel after regular toothbrushing (test), the other without (control). RESULTS: Although oral hygiene itself had a similar positive influence on the improvement of all the clinical indexes for test and control, the treatment with HA gel showed a greater effect almost always statistically significant. BOP in the HA gel treated areas had a decrease of 92.7% and GI of 96.5%, whereas controls 75.8% and 79.0% respectively. The difference of PPD in both areas was statistically significant (p<0.01) in favour of the HA gel treated zone. Also PAL and Pl were reduced more with gel than with oral hygiene alone, although this did not reach a statistical significant difference. CONCLUSION: It appears that an esterified gel form of HA has shown an effect in reducing the gingival inflammation when used as an adjunct to mechanical home plaque control and that it could be successfully used to improve the periodontal clinical indexes. This pilot study will gain substantial scientific significance when both a higher number of patients can be utilized and also by adding any possible further biological information, as with immunocytochemistry and histology.

Usefulness of transcatheter patent foramen ovale closure in migraineurs with moderate to large right-to-left shunt and instrumental evidence of cerebrovascular damage.

Transcatheter patent foramen ovale (PFO) closure might be effective in improving migraines. To assess the efficacy of PFO closure in migraineurs with a moderate to large right-to-left shunt and instrumental evidence of embolic cerebral damage, 76 highly symptomatic migraineurs were prospectively investigated. The presenting clinical syndrome was stroke in 16 patients, repeated transient ischemic attack in 32 patients, and lone migraine associated with cerebral ischemic lesions on magnetic resonance imaging in 28 patients. Migraine severity was assessed before PFO closure and monthly for 6 months after discontinuation of antiplatelet therapy. At the end of 12 months of follow-up, the averaged postprocedural total score was compared with the baseline score. Transcatheter PFO closure was successful in all patients, and the 12-month PFO closure rate was 97%. The baseline total migraine score was similar in patients with stroke, transient ischemic attack, and lone migraine (6.8 +/- 1.6, 6.7 +/- 1.4, and 6.9 +/- 1.7 respectively, p = NS). After a mean follow-up of 13.7 +/- 2.4 months, no recurrent cerebrovascular episodes had occurred. At the end of the follow-up period, a significant reduction in the total migraine score was observed in all groups, regardless of the initial clinical presentation. Migraine was completely abolished in 35 patients (46%), improved in 27 (36%), and unchanged in 14 (18%). The proportion of patients with migraine suppression and improvement was similar in the 3 groups. In conclusion, in highly symptomatic migraineurs with previous ischemic cerebral events and instrumental evidence of cerebral embolism, transcatheter PFO closure can result in improvement of migraine severity in a high percentage of patients.

[Percutaneous closure of patent foramen ovale: a wise approach]. / Indicazioni alla chiusura percutanea del forame ovale pervio: una questione di buon senso.

Patent foramen ovale (PFO) is a remnant of the normal fetal circulation consisting in a communication between septum primum and septum secundum. Postnatally, the two septa fuse completing separation of the atria. In 25% of normal individuals incomplete fusion leads to the persistence of the flap valve leaving a PFO. In the recent years a variety of clinical conditions has been associated with or attributed to PFO. In particular, PFO has been implicated in the pathogenesis of cryptogenic stroke/transient ischemic attack due to paradoxical embolism and to the pathogenesis of migraine headache. PFO has also been associated with decompression illness in divers and to minor diseases such as platypnea-orthodeoxia syndrome and high-altitude pulmonary edema. Meta-analyses and observational studies indicate that the prevalence of PFO is approximately 3-fold higher in patients with cryptogenic stroke and migraineurs compared controls. Conversely, observational evidences indicate a 2-3-fold increased prevalence of migraine and cerebrovascular events in PFO carriers. Observational studies and meta-analyses suggest that, compared to optimal medical treatment, transcatheter closure of PFO might significantly reduce the recurrence of ischemic cerebrovascular events in patients with previous stroke/transient ischemic attack; however, albeit mechanical closure of PFO is an attractive alternative to medical therapy, randomized trials supporting the efficacy of this approach have not been completed. Furthermore, about 80% of patients undergoing PFO closure for nonmigraine indications reported improvement in their migraine symptoms. However, these studies were predominantly retrospective, nonrandomized and conducted in highly selected populations. The recently published MIST trial, the only randomized study available, failed to demonstrate a significant favorable effect of PFO closure for migraine resolution and/or migraine improvement. At present, as insufficient evidence exists to support transcatheter PFO closure for prevention of cryptogenic stroke recurrence as well as for migraine therapy, and considering that the procedure is not riskless (major complications occurring in 1.5-2% of patients whose PFO was closed), a very prudent and wise approach is imperative in individual patients when this therapeutic strategy is carried out.

Jugular approach for percutaneous closure of atrial septal defect.

One hundred and forty-two consecutive procedures of percutaneous closure or atrial septal defect were approached by cannulation of the right femoral vein. In 3 of them, the internal jugular vein approach was also necessary because of azygos continuation or unsuccessful device implantation due to inadequate septal alignment. In all of them, device implantation was successfully performed through this alternative percutaneous vascular approach.

Prevalence and prognosis of atrial septal aneurysm in high risk fetuses without structural heart defects.

BACKGROUND: The aim of this study was to evaluate the prevalence and prognostic implications of the association between atrial septal aneurysm (ASA) and fetal arrhythmias in a population of high risk fetuses. METHODS: One thousand three hundred and two fetal echocardiograms performed during high risk pregnancies from the 17th to the 41st week of gestation were retrospectively evaluated for the presence of ASA and/or arrhythmias. An ASA was defined as redundant tissue extending at least halfway across the left atrium. Patients with an ASA were distinguished in two subgroups according to whether there was (subgroup 1) or was not (subgroup 2) cyclical contact of the atrial septum with the left atrial wall or with the mitral valve. Arrhythmias were documented during mono/two-dimensional echocardiography and Doppler evaluation. RESULTS: Out of 1223 patients considered for the study, 93 (7.6%) fetuses had an ASA; among these 93 fetuses, 33 (36%) had premature atrial beats (p < 0.001). Ten of these patients were included in subgroup 1, and 7 of them (70%) exhibited premature atrial beats (p = 0.016 vs subgroup 2). No arrhythmias other than premature atrial beats were observed in these patients. None of them received any therapy during observation. All of them developed a regular sinus rhythm within 3 months of life. CONCLUSIONS: On the basis of these data, we can speculate that, if accurately searched for, ASA is often present (7.6%) and is likely to represent a mechanical stimulus for the generation of premature atrial beats. Indeed, our data show an important correlation between the degree of bulging and the presence of arrhythmias, supporting the hypothesis of a mechanical stimulus. However, the observed arrhythmias did not appear to be prone to degeneration. In conclusion, ASA observed during fetal life is often associated with premature atrial beats, which are apparently in direct relation with the degree of bulging of the atrial septum. On the other hand, an ASA almost invariably disappears at birth and is not associated with major arrhythmias.

Acute left ventricular failure after transcatheter closure of a secundum atrial septal defect in a patient with coronary artery disease: a critical reappraisal.

We report a case of acute left ventricular failure after transcatheter closure of a single secundum atrial septal defect in a 68-year-old man with coronary artery disease. Just before the procedure, two coronary lesions had been treated with direct stenting. Transcatheter closure of atrial septal defects should always be deferred in ischemic heart disease patients who need percutaneous myocardial revascularization.