OBJECTIVES: To assess international trends and patterns of prenatal diagnosis of critical congenital heart defects (CCHDs) and their relation to total and live birth CCHD prevalence and mortality. SETTING: Fifteen birth defect surveillance programmes that participate in the International Clearinghouse for Birth Defects Surveillance and Research from 12 countries in Europe, North and South America and Asia. PARTICIPANTS: Live births, stillbirths and elective terminations of pregnancy for fetal anomaly diagnosed with 1 of 12 selected CCHD, ascertained by the 15 programmes for delivery years 2000 to 2014. RESULTS: 18 243 CCHD cases were reported among 8 847 081 births. The median total prevalence was 19.1 per 10 000 births but varied threefold between programmes from 10.1 to 31.0 per 10 000. CCHD were prenatally detected for at least 50% of the cases in one-third of the programmes. However, prenatal detection varied from 13% in Slovak Republic to 87% in some areas in France. Prenatal detection was consistently high for hypoplastic left heart syndrome (64% overall) and was lowest for total anomalous pulmonary venous return (28% overall). Surveillance programmes in countries that do not legally permit terminations of pregnancy tended to have higher live birth prevalence of CCHD. Most programmes showed an increasing trend in prenatally diagnosed CCHD cases. DISCUSSION AND CONCLUSIONS: Prenatal detection already accounts for 50% or more of CCHD detected in many programmes and is increasing. Local policies and access likely account for the wide variability of reported occurrence and prenatal diagnosis. Detection rates are high especially for CCHD that are more easily diagnosed on a standard obstetric four-chamber ultrasound or for fetuses that have extracardiac anomalies. These ongoing trends in prenatal diagnosis, potentially in combination with newborn pulse oximetry, are likely to modify the epidemiology and clinical outcomes of CCHD in the near future.

• Klíčová slova
• critical congenital heart defects, epidemiology, prenatal diagnosis,
• MeSH
• lidé MeSH
• novorozenec MeSH
• prenatální diagnóza * statistika a číselné údaje   trendy   MeSH
• prevalence MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• vrozené srdeční vady diagnóza   epidemiologie   mortalita   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Asie epidemiologie   MeSH
• Evropa epidemiologie   MeSH
• Jižní Amerika epidemiologie   MeSH
• Severní Amerika epidemiologie   MeSH

Objective: The main aim of this study was to compare the prevalence of congenital heart defects (CHDs) between pregnant women with and those without the risk factors. The secondary aim was to determine the influence of the specific risk factors, divided into subgroups, on the development of the CHD. Methods: The presented results were obtained over the course of a 15-year study between years 2002 and 2016. Fetal echocardiography was performed as a planned screening examination during the second trimester of gravidity. A total of 35,831 singleton pregnancies were examined at our center. Risk factors for the development of CHDs were analyzed and divide into the following groups: (i) maternal age ≥35 years; (ii) mother-related risk factors; (iii) pregnancy- and fetus-related risk factors; (iv) pregnancy after in vitro fertilization (IVF); (v) history of CHDs in the first-degree family member; (vi) history of CHDs in the second-degree family member; and (vii) positive genetic family history. Results: The risk factors were identified in 25% (8990/35,831) of pregnancies. In total, CHDs were detected in 1.1% (394/35,831) of fetuses. The prevalence rate of CHDs was higher in the pregnancies with than in those without the risk factors (2.5% [221/8990] versus 0.6% [173/26,841]; p < .0001). The presence of pregnancy- and fetus-related risk factors (odds ratio [OR], 6.5; 95% confidence interval [CI], 4.3-9.7) and pregnancy after IVF (OR, 2.8; 95% CI, 1.5-5.2) were found to be independent risk factors of CHDs. Conclusions: The presence of specific risk factors is related to the increasing prevalence of CHDs. Pregnancy- and fetus-related risk factors and in vitro fertilization were found to be the independent risk factors of CHD.

• Klíčová slova
• Congenital heart defect, fetal echocardiography, prenatal screening, risk factor,
• MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé MeSH
• novorozenec MeSH
• prevalence MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• těhotenství MeSH
• vrozené srdeční vady epidemiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

AIM: To study congenital heart defects (CHDs), evaluate their relation to extra-cardiac pathologies, and assess the significance of prenatal diagnostics for heart diseases. METHODS: Data from 1999-2017 were analyzed for the incidence of significant CHDs in fetuses (prenatal ultrasound/echocardiography) and children, including, where applicable, autopsy data and genetic evaluation. RESULTS: Among 220,400 fetuses, 819 (3.7 cases per 1000) significant CHDs were observed. Of the total, 53% (435/819) of CHDs were diagnosed prenatally. The heart defect was an isolated impairment in 78% (640/819), associated with a genetic impairment in 16% (128/819), and with extra-cardiac malformations without genetic pathology in 6% (51/819). Chromosomal aberrations were diagnosed prenatally in 70% (90/128) of those affected and extra-cardiac conditions in 86% (44/51). The CHD and genetic pathology association was more frequent prenatally [21% (90/435) vs. postnatally: 10% (38/384; P<0.0001)], as was the association between CHD with other extra-cardiac pathology and a normal karyotype [prenatally: 10% (44/435) vs. postnatally: 2% (7/384; P<0.0001)]. CONCLUSION: Heart defects are most frequently isolated, with genetic and other extra-cardiac anomalies in about one third of cases, significantly linked to prenatal diagnostics.

• Klíčová slova
• aneuploidy, congenital heart defect, extracardiac malformation, fetal echocardiography, genetic abnormality, screening,
• MeSH
• chromozomální aberace embryologie   MeSH
• echokardiografie MeSH
• gestační stáří MeSH
• incidence MeSH
• lidé MeSH
• novorozenec MeSH
• pitva MeSH
• prenatální diagnóza * statistika a číselné údaje   MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• ultrasonografie prenatální MeSH
• vrozené srdeční vady diagnostické zobrazování   embryologie   mortalita   MeSH
• výsledek těhotenství MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: The aim of this retrospective study was to determine the detection rate of the pathogenic copy number variants (CNVs) in a cohort of 33 foetuses - 32 with CHD (congenital heart defects) and 1 with kidney defect, after exclusion of common aneuploidies (trisomy 13, 18, 21, and monosomy X) by karyotyping, Multiplex ligation - dependent probe amplification (MLPA) and chromosomal microarray analysis (CMA). We also assess the effectivity of MLPA as a method of the first tier for quick and inexpensive detection of mutations, causing congenital malformations in foetuses. METHODS: MLPA with probe mixes P070, P036 - Telomere 3 and 5, P245 - microdeletions, P250 - DiGeorge syndrome, and P311 - CHD (Congenital heart defects) was performed in 33 samples of amniotic fluid and chorionic villi. CMA was performed in 10 relevant cases. RESULTS: Pathogenic CNVs were found in 5 samples: microdeletions in region 22q11.2 (≈2 Mb) in two foetuses, one distal microdeletion of the 22q11.2 region containing genes LZTR1, CRKL, AIFM3 and SNAP29 (≈416 kb) in the foetus with bilateral renal agenesis, 8p23.1 (3.8 Mb) microdeletion syndrome and microdeletion in area 9q34.3 (1.7 Mb, Kleefstra syndrome). MLPA as an initial screening method revealed unambiguously pathogenic CNVs in 15.2 % of samples. CONCLUSION: Our study suggests that MLPA and CMA are a reliable and high-resolution technology and should be used as the first-tier test for prenatal diagnosis of congenital heart disease. Determination of the cause of the abnormality is crucial for genetic counselling and further management of the pregnancy.

• Klíčová slova
• bilateral renal agenesis, clinical variability, congenital heart defect, copy number variants,
• MeSH
• lidé MeSH
• pilotní projekty MeSH
• plod MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• transkripční faktory genetika   MeSH
• variabilita počtu kopií segmentů DNA * genetika   MeSH
• vrozené srdeční vady * diagnóza   genetika   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• LZTR1 protein, human MeSH Prohlížeč
• transkripční faktory MeSH

BACKGROUND: Severe or critical congenital heart defects (CHDs) constitute one third of the heart defect cases detected only after birth. These prenatally unrecognised defects usually manifest as cyanotic or acyanotic lesions and are diagnosed postnatally at various times. The aim of the study was to identify their clinical symptoms and determine individual risk periods for CHD manifestation. METHODS: Data were assessed retrospectively based on a cohort of patients born between 2009 and 2018 in a population of 175,153 live births. Occurrence of the first symptoms of CHD was classified into: early neonatal (0-7 days), late neonatal (8-28 days), early infancy (1-6 months), or late infancy (6-12 months). The first symptom for which the child was referred to a paediatric cardiologist was defined as a symptom of CHD. RESULTS: There were 598 major CHDs diagnosed in the studied region, 91% of which were isolated anomalies. A concomitant genetic disorder was diagnosed in 6% of the cases, while 3% presented extracardiac pathology with a normal karyotype. In total, 47% (282/598) of all CHDs were not identified prenatally. Of these, 74% (210/282) were diagnosed as early neonates, 16% (44/282) as late neonates, and 10% (28/282) as infants. The most common symptoms leading to the diagnosis of CHD were heart murmur (51%, 145/282) and cyanosis (26%, 73/282). Diagnosis after discharge from the hospital occurred in 12% (72/598) of all major CHDs. Ventricular septal defect and coarctation of the aorta constituted the majority of delayed diagnoses. CONCLUSIONS: In conclusion, murmur and cyanosis are the most common manifestations of prenatally undetected CHDs. Although most children with major CHDs are diagnosed as neonates, some patients are still discharged from the maternity hospital with an unidentified defect.

• Klíčová slova
• Congenital heart defect, Cyanosis, Murmur, Symptom,
• MeSH
• cyanóza etiologie   MeSH
• defekty komorového septa * MeSH
• dítě MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• vrozené srdeční vady * diagnóza   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The incidence of congenital heart defects was studied prospectively in all 664 218 children born in 1977 to 1984. Those suspected of having a heart disease were examined at the centre specialized in pediatric cardiology. All children who died were autopsied and those where a heart defect was proved were included in our series. In total, 4409 infants (6,64/1000 live births) were born with a heart defect in Bohemia. Differences from one year to another were not statistically significant. The incidence of infants with a heart defect was highest in October, lowest in December, June and July (p less than 0.05). Seasonal incidence of individual forms of heart defects differed also. The seasonal variation was not influenced by the total number of live births. The high incidence of congenital heart defects in infants born in October and November coincides with the epidemics of influenza in early pregnancy.

• MeSH
• incidence MeSH
• lidé MeSH
• novorozenec MeSH
• roční období * MeSH
• vrozené srdeční vady epidemiologie   etiologie   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Československo epidemiologie   MeSH

AIM: To assess the outcome and mortality trend in newborns undergoing corrective surgery for congenital heart defect. METHOD: We reviewed the hospital records of 1,033 neonates under 30 days of life, who had congenital heart defects operated on at the Kardiocentrum, Motol University Hospital in Prague, Czech Republic, during 1977-2001. Early and late mortality and reoperation rates were analyzed. RESULTS: A total of 1,156 operations were performed in 1,033 neonates. Obstructive lesions were surgically treated in 56%, left-to-right shunts in 21%, and complex conotruncal lesions in 23% of the cases. Total correction has been achieved in 62% of the neonates. Most operations (75%) were performed in the first two weeks of neonate s life. Early 30-day hospital mortality was 13%. Late mortality, after the discharge from the hospital, was 10%. In the last three years, the hospital mortality rate decreased to about 2%. Out of 590 reinterventions in 379 neonates, with the mortality of 6%, 229 were secondary staged corrections and 190 further palliative procedures aimed mostly toward Fontan or Rastelli type of circulation. Residual or recurrent defects were solved in 62 neonates. There were 30 valve replacements, with 18 mechanical valves and 12 pulmonary valve autotransplantations (the Ross procedure). The homograft valved conduit was used in 38 children. CONCLUSION: Most newborns with critical congenital heart defects can undergo corrective operation under acceptable risk. Due to complex improvements in perioperative, anaesthetic, surgical, and postoperative care, contemporary hospital mortality can be reduced to 1-3%. Palliative procedures still play an important role in the staged treatment of severe complex heart defects in neonates.

• MeSH
• analýza přežití MeSH
• kardiochirurgické výkony mortalita   statistika a číselné údaje   MeSH
• lidé MeSH
• mortalita v nemocnicích MeSH
• nemocnice univerzitní MeSH
• novorozenec MeSH
• vrozené srdeční vady klasifikace   chirurgie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Together, heart failure and arrhythmia represent the most important cardiovascular sources of morbidity and mortality among adults with congenital heart disease (ACHDs). Although traditionally conceptualized as operating within 2 distinct clinical silos, these scenarios frequently coexist within the same individual; consequently the mechanistic, therapeutic, and prognostic overlap between them demands increased recognition. In fact, given the near ubiquity of heart failure and arrhythmia among ACHDs, there is perhaps no other arena within cardiology where this critical intersection is more frequently observed. Optimal care for ACHDs therefore requires a heightened awareness of the relevant interactions as well as the pharmacologic and interventional resources that are increasingly available to the treating cardiologist. This review explores and highlights the overlap between these 2 fields to recommend a parallel, yet interactive, multidisciplinary approach to clinical management. Congenital heart disease categories are broken down into their archetypal subtypes to highlight subtleties of the pathophysiology, evaluation, and therapeutic approach.

• Klíčová slova
• adults with congenital heart disease, arrhythmia, heart failure,
• MeSH
• dospělí MeSH
• kardiologie * MeSH
• kardiologové * MeSH
• lidé MeSH
• srdeční arytmie etiologie   terapie   MeSH
• srdeční selhání * komplikace   terapie   MeSH
• vrozené srdeční vady * komplikace   terapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Congenital heart disease is the most common type of birth defect, accounting for one-third of all congenital anomalies. Using whole-exome sequencing of 2718 patients with congenital heart disease and a search in GeneMatcher, we identified 30 patients from 21 unrelated families of different ancestries with biallelic phospholipase D1 (PLD1) variants who presented predominantly with congenital cardiac valve defects. We also associated recessive PLD1 variants with isolated neonatal cardiomyopathy. Furthermore, we established that p.I668F is a founder variant among Ashkenazi Jews (allele frequency of ~2%) and describe the phenotypic spectrum of PLD1-associated congenital heart defects. PLD1 missense variants were overrepresented in regions of the protein critical for catalytic activity, and, correspondingly, we observed a strong reduction in enzymatic activity for most of the mutant proteins in an enzymatic assay. Finally, we demonstrate that PLD1 inhibition decreased endothelial-mesenchymal transition, an established pivotal early step in valvulogenesis. In conclusion, our study provides a more detailed understanding of disease mechanisms and phenotypic expression associated with PLD1 loss of function.

• Klíčová slova
• Cardiology, Cardiovascular disease, Genetic diseases, Genetics, Heart failure,
• MeSH
• alely * MeSH
• fosfolipasa D * genetika   metabolismus   MeSH
• lidé MeSH
• mutace ztráty funkce * MeSH
• nemoci srdečních chlopní * enzymologie   genetika   MeSH
• vrozené srdeční vady * enzymologie   genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• fosfolipasa D * MeSH
• phospholipase D1 MeSH Prohlížeč

Lung function tests (i.e., spirometry, flow volume, and body plethysmography) were performed in 213 patients (age 6-21 years, mean 11.3 years) with hemodynamically significant congenital heart defects: atrial septal defect, ventricular septal defect (VSD), tetralogy of Fallot, aortic stenosis and coarctation of the aorta. We measured lung vital capacity, total lung capacity (TLC), residual volume (RV), the percentage ratio of the latter two measurements (%RV/TLC), maximal expiratory flow rates at 25% and 50% of vital capacity, and specific airway conductance. Pulmonary restriction dominated in patients with tetralogy of Fallot; pulmonary hyperinflation was more frequent in patients with VSD and coarctation of the aorta; and obstruction of the airways was observed most frequently in patients with tetralogy of Fallot. In conclusion, we found a range of pathologic lung function parameters in patients with hemodynamically significant congenital heart defects.

• MeSH
• dítě MeSH
• dospělí MeSH
• hemodynamika MeSH
• lidé MeSH
• mladiství MeSH
• plíce patofyziologie   MeSH
• respirační funkční testy MeSH
• vrozené srdeční vady patofyziologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH