Ida Jovanovic

Pericardial Disease in Pregnancy

Abstract.Background: There is no evidence that pregnancy affects susceptibility to pericardial disease. However, when such a condition occurs, its proper diagnosis and management may be crucial for the outcome of the pregnancy. Incidence and Diagnosis: Hydropericardium is the most frequent form of pericardial involvement in pregnancy. It is typically a small, clinically silent pericardial effusion present in the third trimester in approximately 40% of healthy pregnant women. Small amounts of fetal pericardial fluid (< 2 mm in echocardiography, in diastole) can be detected after 20 weeks of gestation. Larger effusions should raise clinical concern for hydrops fetalis, Rh disease, hypoalbuminemia, and infectious or autoimmune disorder. Wide varieties of etiologic forms of pericardial diseases occur sporadically in pregnant women. Significant symptoms, electrocardiographic changes, or physiologic impairment warrant hospitalization. Treatment: Most pericardial disorders are managed during pregnancy as in nonpregnant patients (i.e., nonsteroidal antiinflammatory drugs for acute, antibiotics and drainage for purulent pericarditis, and corticosteroids for systemic autoimmune disorders). However, colchicine is contraindicated in pregnancy, and pericardiocentesis should be performed only for very large effusions causing clinical signs of cardiac tamponade or if presence of suppurative, tuberculous or neoplastic pericardial effusion is suspected. Echocardiographic guidance of pericardiocentesis is preferred to fluoroscopic guidance in order to avoid fetal X-ray exposure. Pericardiectomy should be reserved for significant pericardial constriction and resistant bacterial infections. Delivery of normal infants in term after pericardiocentesis or pericardiectomy is expected, whenever natural history of causative disease allows. Pericardiectomy itself is not a contraindication for subsequent successful pregnancies.Zusammenfassung.Hintergrund: Hinweise dafür, dass eine Schwangerschaft zur Entstehung von Perikarderkrankungen prädisponiert oder deren Ausbildung beeinflusst, gibt es nicht. Wenn aber während der Schwangerschaft eine Perikarderkrankung auftritt, sind eine schnelle Diagnose und die richtige Behandlung von großer Bedeutung. Inzidenz und Diagnose: Die häufigste Form eines Perikardergusses während der Schwangerschaft ist das “Hydroperikard”. Es handelt sich typischerweise um das Auftreten eines kleinen, klinisch nicht relevanten Perikardergusses im dritten Trimenon der Schwangerschaft. Bei ca. 40% aller gesunden Schwangeren ist ein solcher minimaler Erguss nachweisbar. In der 20. Schwangerschaftswoche kann auch bei den Feten ein kleiner Perikarderguss nachgewiesen werden, der in der fetalen Echokardiographie eine Separation von < 2 mm zeigen sollte. Größere Ergüsse sind meist das erste klinische Zeichen für einen Hydrops fetalis, eine Rhesus-Blutgruppenunverträglichkeit, eine Hypoalbuminämie bzw. infektiöse oder autoimmune Erkrankungen des Fetus und/oder der Mutter.Die Ätiologie der Perikarderkrankungen der Mutter während der Schwangerschaft ist vielfältig, wobei die akute virale Perikarditis und Perikardergüsse im Rahmen systemischer autoimmuner Erkrankungen die häufigsten Ursachen darstellen. Selten findet man auch Perikardergüsse bei Schwangeren im Rahmen von Tumorerkrankungen oder einer Tuberkulose. Wenn starke präkordiale Schmerzen, Veränderungen im EKG und eine deutliche Beeinträchtigung der Belastungsfähigkeit auftreten, ist eine Klinikeinweisung unumgänglich. Therapie: Die meisten Perikarderkrankungen bei Schwangeren werden behandelt wie die von Nichtschwangeren, d.h. mit nichtsteroidalen antiinflammatorischen Medikamenten bei akuter Perikarditis, mit Antibiotika und ggf. einer Drainage bei eitrigen Perikardergüssen bzw. der Gabe von Kortikosteroiden bei autoimmunen Systemerkrankungen. Die Gabe von Colchicin ist während der Schwangerschaft kontraindiziert. Eine Perikardpunktion wird nur bei großen Perikardergüssen mit den klinischen Zeichen einer akuten Tamponade bzw. bei Verdacht auf Tuberkulose, infektiösen Erguss oder Tumorerkrankung durchzuführen sein. In diesen wenigen Fällen ist eine echokardiographisch gesteuerte Punktion angebracht, um eine Strahlenbelastung des Ungeborenen zu vermeiden. Eine Perikardektomie sollte nur bei perikardialer Konstriktion und schwerer bakterieller Infektion durchgeführt werden.Die Prozeduren Perikardpunktion und Perikardektomie allein haben, vom Interventions- bzw. Operationsrisiko abgesehen, keinen negativen, sondern eher einen günstigen prognostischen Einfluss auf die Schwangerschaft.Es gibt bislang keine ausreichenden Daten dafür, dass eine Perikardergussbildung in einer vorausgegangenen Schwangerschaft bei erneuter Gravidität zu einem Rezidiv führt. Liegen gleichzeitig allerdings eine linksventrikuläre Dilatation und Dysfunktion vor, ist, wie im Beitrag “Schwangerschaft und Kardiomyopathie” ausgeführt, nach den Empfehlungen der European Society of Cardiology (ESC) von einer erneuten Schwangerschaft abzuraten.

4q34.1–q35.2 deletion in a boy with phenotype resembling 22q11.2 deletion syndrome

Small terminal or interstitial deletions involving bands 4q34 and 4q35 have been described in several patients with a relatively mild phenotype such as mild to moderate intellectual disability and minor dysmorphic features. We present a boy born from unrelated parents with a de novo 4q34.1–q35.2 deletion and clinical features resembling 22q11.2 deletion syndrome. To the best of our knowledge, this is the first reported patient with 4q34–q35 deletion and phenotype resembling 22q11.2 deletion syndrome without fifth finger anomalies as a specific feature of 4q- syndrome. G-banding karyotyping disclosed the deletion, which was further delineated by microarray comparative genomic hybridization. Fluorescence in situ hybridization and multiplex ligation-dependent probe amplification analyses did not reveal rearrangements of 22q11.2 region. MLPA confirmed the deletion within the 4q35.2 region. Conclusion: Given the considerable clinical overlaps between the 22q11.2 deletion syndrome and clinical manifestation of the patient described in this study, we propose that region 4q34.1–q35.2 should be considered as another region associated with phenotype resembling 22q11.2 deletion syndrome. We also propose that distal 4q deletions should be considered in the evaluation of patients with phenotypic manifestations resembling 22q11.2 deletion syndrome in whom no 22q11.2 microdeletion was detected, even in the absence of distinctive fifth finger anomalies. Additionally, we underline the importance of applying array CGH that enables simultaneous genome-wide detection and delineation of copy number changes (e.g., deletions and duplications).

Echocardiographic analysis of the subtypes of right ventricular restrictive physiology in surgically treated patients with tetralogy of Fallot.

BACKGROUND Our study focuses on echocardiographic assessment of the right ventricular diastolic function and adaptive right ventricular response to volume overload resulting from pulmonary and tricuspid regurgitation in surgically treated patients with tetralogy of Fallot. METHOD AND RESULTS We included 60 patients subsequent to surgical correction of tetralogy of Fallot, dividing them into two groups - a group of 18 patients with restrictive physiology, having antegrade flow to the pulmonary arteries greater than 30 centimetres per second in late diastole in five consecutive beats, and a group of 42 patients with non-restrictive physiology. Based on the cardiothoracic ratio, being more or equal to, or less than 0.55, we further divided those with restrictive physiology into a group of 14 patients deemed to have primary restriction, and the other 4 patients considered to have secondary or acquired restriction. Those with non-restrictive physiology were divided into groups of 16 patients with a small heart, and 26 patients with a large heart. A fraction of the venous retrograde diastolic flow in the hepatic vein greater or equal to 30 centimetres is important for distinguishing between the subgroup with primary restriction and the other subgroups. In the four patients with secondary restriction, anterograde diastolic flow in the pulmonary artery greater than 30 centimetres per second was recorded after the average period of follow-up of 2.4 years. The mean value of the pulmonary regurgitant jet pressure half-time was higher in the subgroup with the secondary restriction in comparison to the nonrestrictive subgroup with large hearts at 152 milliseconds with standard deviation of 36 milliseconds versus 85 milliseconds with standard deviation of 11 milliseconds, p less than 0.05. This was significantly lower in comparison to those with primary restriction, where the value was 238 milliseconds, with standard deviation of 42 milliseconds, p less than 0.02. CONCLUSION Echocardiographic analysis offers great possibilities for assessment of right ventricular diastolic function, identifying in particular those with restrictive physiology, its interrelation with pulmonary and tricuspid regurgitation, as well as timing and selection of patients for re-intervention.

Evaluation of myocardial perfusion and function by gated single-photon emission computed tomography technetium-99m methoxyisobutylisonitrile in children and adolescents with severe congenital heart disease.

ObjectivesThe value of gated single-photon emission computed tomography technetium-99m methoxyisobutylisonitrile (gated SPECT 99mTc-MIBI) in children is not yet established probably because gated SPECT 99mTc-MIBI has rarely been used in pediatric clinical and research studies. The purpose of this study was to evaluate perfusion abnormalities and left ventricular (LV) function by gated SPECT 99mTc-MIBI in children and adolescents with severe congenital heart disease (CHD). MethodsSeventeen children and adolescents with severe CHD (11 boys and six girls, mean age 11±4 years) underwent 2-day rest–stress (11 boys) or 1-day rest (six girls) gated SPECT 99mTc-MIBI. Myocardial perfusion was evaluated by a 17-segment model with a 5-point score to derive the summed stress score, the summed rest score (SRS), and the summed difference score based on the 4D-MSPECT software results. The extent of myocardial perfusion abnormalities was also expressed as a percentage of the LV size. The 4D-MSPECT software was used to calculate LV end-diastolic volume, end-systolic volume (ESV), and ejection fraction (EF). ResultsReversible myocardial perfusion defect was found in 7 of 11 children (64%) who underwent rest–stress gated SPECT 99mTc-MIBI. The LV segments involved were anterior, anteroseptal, anterolateral, apical and inferior. These seven children showed significantly larger perfusion abnormalities on stress compared with rest study (18±5 vs. 7±4%, P<0.01) and higher summed stress score compared to SRS (11±4 vs. 4±2, P<0.01). Children and adolescents with myocardial ischemia had significantly lower poststress EF than rest EF (53±12 vs. 59±11%, P<0.05) and significantly higher poststress ESV than rest ESV (81±24 vs. 61±25 ml, P<0.05). In six children evaluated only at rest, perfusion defects involved anterior, anteroseptal and apical, or inferolateral segments, accounting for 31±12% of LV and with SRS of 12±5. Their global LV parameters were: end-diastolic volume 118±23 ml, ESV 56±16 ml, EF 51±10%. ConclusionPoststress and rest-gated SPECT 99mTc-MIBI results indicate that children and adolescents with severe CHD show a range of abnormalities in myocardial perfusion and LV function, which is useful for determining functional importance of morphological malformations. Thus, gated SPECT 99mTc-MIBI provides complementary information that may guide clinical decision making in children and adolescents with severe CHD.

Prenatal growth retardation, microcephaly, and eye coloboma in infant with multiple congenital anomalies: Further delineation of presumed new dysmorphic syndrome

BACKGROUND Ten years ago an unusual association of prenatal growth retardation, microcephaly, coloboma of the iris/eye anomalies, congenital heart defects, and urogenital anomalies was reported for the first time in three siblings. Autosomal recessive inheritance was presumed. This finding has been included in London Winter-Baraitser Dysmorphology Database as a separate entity, but still has not been classified as a distinct syndrome. CASE We report an infant with an association of prenatal growth retardation, microcephaly, facial dysmorphism, eye anomalies, congenital heart defects, and testis retention. Mild craniofacial dysmorphism consists of sloped forehead, bulbous nose tip, and micrognathia. Eye anomalies include coloboma of the iris, choroidea, and optic nerve as well as lens dislocation. The patient also presents with ventricular and atrial septal defects, hypoplastic mitral valve, persistent left superior vena cava, accessory spleen, and club foot. CONCLUSIONS To the best of our knowledge, this is the second family and the fourth case with this pattern of birth defects reported worldwide so far. We presume that this combination of multiple congenital anomalies and growth retardation constitutes a newly recognized syndrome of likely autosomal recessive inheritance. So far no data suggest etiological impact of consanguinity, parental age, or environmental factors.

Differences in speech and language abilities between children with 22q11.2 deletion syndrome and children with phenotypic features of 22q11.2 deletion syndrome but without microdeletion.

BACKGROUND 22q11.2DS is the most common microdeletion syndrome in humans, usually associated with speech and language delay (SLD). Approximately 75% of children with 22q11.2 microdeletion have congenital heart malformations (CHM) which after infant open-heart surgery might lead to SLD. AIMS The purpose of this study was to determine whether factors associated with microdeletion contribute to SLD in children with 22q11.2DS. METHODS AND PROCEDURES We compared speech and language abilities of two groups of school-aged children: those with 22q11.2 microdeletion (E1) and those with the phenotype resembling 22q11.2DS but without the microdeletion (E2). An age-matched group of typically developing children was also tested. OUTCOMES AND RESULTS The obtained results revealed that children from group E1 have lower level of speech and language abilities compared to children from group E2 and control group. Additionally, mild to moderate SLD was detected in children from group E2 compared to children from the control group. CONCLUSIONS AND IMPLICATIONS The obtained results imply that both CHM after infant open-heart surgery and other factors associated with 22q11.2 microdeletion, contribute to SLD in patients with 22q11.2 microdeletion. Based on this, we could postulate that there is/are some potential candidate gene(s), located in the 22q11.2 region, whose function could be important for speech and language development.

Mowat-Wilson syndrome: A case report

INTRODUCTION Mowat-Wilson syndrome (MWS) is characterised by severe mental retardation and multiple congenital anomalies. Key features for diagnosis are specific facial dysmorphism with uplifted ear lobes and Hirschsprungs disease. Ganglionic disorders of the colon, both the number of ganglion cells and the length of the aganglionic segment vary significantly in these patients. The disease is caused by ZFHX1B gene mutation. The management of MWS is symptomatic. CASE OUTLINE We report a four-year-old boy with mental retardation, specific facial dysmorphy and multiple anomalies. During prenatal follow-up intrauterine growth retardation was revealed. Karyotype was normal. Clinical findings showed that growth and mental retardation, gastrointestinal disturbance and heart defect were predominant. A gastrostoma was inserted. Hypoganglionosis of the colon caused severe obstipation. He had a severe stenosis of the pulmonary artery and was a candidate for cardiac surgery. There were several attempts to establish diagnosis, but so far, without results CONCLUSION Hirschsprungs disease/hypoganglionosis of the colon associated with other congenital anomalies or mental retardation require evaluation for dysmorphic syndromes. One of them is MWS, presented in this report.

A rare association of interrupted aortic arch type C and microdeletion 22q11.2

Microdeletion 22q11.2 is associated with a variety of findings, and the most common are cardiac defects. It is very frequently associated with interrupted aortic arch (IAA) type B and very rarely with type A and type C. Here we report the first case of IAA type C associated with 22q11.2 deletion in Serbia and, to the best of our knowledge, the fourth case described worldwide so far. By this report we would like to point out that all patients with IAA type C who have additional features specific for 22q11.2 microdeletion syndrome should be screened for the presence of this deletion.

Improving the Diagnosis of Children with 22q11.2 Deletion Syndrome: A Single-center Experience from Serbia.

ObjectiveThe incidence of the 22q11.2 microdeletion among children who have at least two out of five major clinical criteria for 22q11.2 deletion syndrome.DesignProspective study.SettingUniversity Children’s Hospital in Belgrade, Serbia between 2005 and 2014.Participants57 patients with clinical characteristics of 22q11.2 deletion syndrome.MethodsStandard G-banding cytogenetic analysis was performed in all children, and the 22q11.2 genomic region was examined using fluorescence in situ hybridization (FISH). For patients with no deletion detected by FISH, multiplex ligationdependent probe amplification (MLPA) analysis was also done in order to detect cryptic deletions of this region and to analyze other genomic loci associated with phenotypes resembling the syndrome. A selected group of patients diagnosed to have 22q11.2 microdeletion by FISH underwent MLPA testing in order to characterize the size and position of deletion.Outcome MeasureThe frequency of 22q11.2 microdeletion among children with at least two of the five major characteristics of 22q11.2 deletion syndrome (heart malformations, facial dysmorphism, T-cell immunodeficiency, palatal clefts and hypocalcemia/hypoparathyroidism)ResultsTypical 22q11.2 microdeletion was detected in 42.1% of patients; heart malformation were identified in all of them, facial dysmorphism in 79.2%, immunological problems in 63.6%, hypocalcemia in 62.5% and cleft palate in 8.3%.ConclusionsA higher detection rate compared to one-feature criterion is obtained when at least two major features of 22q11.2 deletion syndrome are taking into consideration. The criteria applied in this study could be considered by centers in lowincome countries.

SAFETY OF ACE INHIBITORS IN CHILDREN WITH HEART FAILURE

Background ACE inhibitors (ACE-I) are a cornerstone in the treatment of children with heart failure. Little is known on the pharmacokinetics (PK) and pharmacodynamics (PD) of enalapril in children. LENA trials will investigate a novel child-appropriate solid drug formulation of enalapril and obtain PK, PD and safety data. For this study clear safety cut-offs need to determined. Aim To review the literature on safety of ACE-I in paediatric heart failure. Methods We searched electronic databases and reference lists of relevant studies. Inclusion criteria were 1. Randomized Controlled Trials (RCT), Controlled trials (CT), case reports or retrospective cohorts. 2. Patients under 18 years with congestive heart failure. 3. Any kind of ACE-I 4. Outcome measures: Mortality, hypotension, renal failure, hyperkalaemia, liver enzyme rise, cough, neutropenia. Results We assessed 12 of 593 articles as relevant: 2 RCTs, 5 CTs, 3 retrospective cohort studies and 2 case reports on a total of 734 children with heart failure. Systematic analyses was hampered by the heterogeneity of the study designs. In summary, we identified renal failure, hypotension and hyperkalemia as the most important side effects. Renal failure was found in 80 patients (11%), hypotension in 33 (4,5%) and hyperkalemia in 5 (0,7%). Five studies (n= 315 children) suggest that young age and low weight increases the risk of renal failure. Conclusions Renal failure, hypotension and hyperkalemia are the most reported adverse events in children on an ACE-I for heart failure. We defined strict adjusting- and stopping rules for enalapril based on an Acute Kidney Injury scale, b. on values of systolic blood pressure and on c. serum levels potassium. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007–2013) under grant agreement n°602295 (LENA).