Showing papers by "Nico A. Blom published in 2016"

2015 ESC Guidelines for the Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death.

Abstract: 2015 ESC Guidelines for the Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death

Arrhythmogenic anatomical isthmuses identified by electroanatomical mapping are the substrate for ventricular tachycardia in repaired tetralogy of Fallot.

Abstract: Aims The majority of ventricular tachycardias (VTs) in repaired tetralogy of Fallot (rTOF) are related to anatomically defined isthmuses. We aimed to identify specific electroanatomical characteristics of anatomical isthmuses (AI) related to VT which may allow for individualized risk stratification and tailored ablation. Methods and results Seventy-four consecutive rTOF patients (40 ± 16 years, 63% male) underwent VT induction and right ventricular electroanatomical voltage and activation mapping during sinus rhythm (SR) to identify the presence and characteristics of AI (isthmus width, length and conduction velocity index [CVi]). Twenty-eight patients were inducible for 41 VTs. All 74 patients had at least one AI. However, AI in patients with VT were longer (22 ± 7 vs. 16 ± 7 mm, P = 0.001), narrower (20 ± 8 vs. 28 ± 11 mm, P < 0.001) and had lower CVi (0.36 ± 0.34 vs. 0.78 ± 0.24 m/s, P < 0.001). Thirty-seven VTs in 24 patients were mapped (pace-, entrainment mapping, and/or VT termination by ablation) to 28 AI. All 28 AI related to VT had a CVi < 0.5 m/s (slow conducting AI (SCAI)). In contrast, 87 of 89 AI of the 46 patients without VT had CVi ≥ 0.5 m/s. Sixty-two patients were discharged without the presence of an SCAI (44 had no SCAI at baseline, 18 underwent ablation of the SCAI) and 10 still had an SCAI (no/failed ablation). During follow-up (50 ± 22 months), no patient without SCAI had any VT, which occurred in 5/10 patients with SCAI ( P < 0.001). Conclusion In rTOF, slow conducting anatomical isthmuses identified by electroanatomical mapping during SR are the dominant substrate for VT allowing individualized risk stratification and preventive ablation.

GNB5 Mutations Cause an Autosomal-Recessive Multisystem Syndrome with Sinus Bradycardia and Cognitive Disability.

Abstract: GNB5 encodes the G protein β subunit 5 and is involved in inhibitory G protein signaling. Here, we report mutations in GNB5 that are associated with heart-rate disturbance, eye disease, intellectual disability, gastric problems, hypotonia, and seizures in nine individuals from six families. We observed an association between the nature of the variants and clinical severity; individuals with loss-of-function alleles had more severe symptoms, including substantial developmental delay, speech defects, severe hypotonia, pathological gastro-esophageal reflux, retinal disease, and sinus-node dysfunction, whereas related heterozygotes harboring missense variants presented with a clinically milder phenotype. Zebrafish gnb5 knockouts recapitulated the phenotypic spectrum of affected individuals, including cardiac, neurological, and ophthalmological abnormalities, supporting a direct role of GNB5 in the control of heart rate, hypotonia, and vision.

Prenatal diagnosis of congenital heart defects: accuracy and discrepancies in a multicenter cohort

Abstract: Objective To examine the accuracy of fetal echocardiography in diagnosing congenital heart disease (CHD) at the fetal medicine units of three tertiary care centers. Methods This was a multicenter cohort study of tertiary echocardiography referrals between 2002 and 2012. Prenatal and postnatal diagnoses were compared and the degree of agreement was classified as ‘correct’ (anatomy correct and the postnatal diagnosis led to a similar outcome as expected), ‘discrepant’ (anatomical discrepancies present but the severity and prognosis of the defect were diagnosed correctly) or ‘no similarity’ (the pre- and postnatal diagnoses differed completely). Results We included 708 cases with CHD for which both prenatal and postnatal data were available. The prenatal diagnosis was correct in 82.1% of cases and discrepancies present were present in 9.9%; however, these did not result in a different outcome. In 8.1% there was no similarity between prenatal and postnatal diagnoses. Disagreement between pre- and postnatal diagnoses occurred significantly more frequently in cases that presented with a normal four-chamber view than in those with an abnormal four-chamber view (5.5% vs 1.9%). Incorrect identification of the outflow tracts and incorrect differentiation between unbalanced atrioventricular septal defect and hypoplastic left heart syndrome were relatively commonly encountered. In many cases with disagreement, trisomy 21, extracardiac anomaly or a high maternal body mass index was present. Conclusions The prenatal diagnosis and estimated prognosis of fetal echocardiography in our tertiary referral centers were appropriate in 92% of cases. Some types of CHD remain difficult to diagnose or rule-out prenatally, therefore awareness and education are of considerable importance. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Guía ESC 2015 sobre el tratamiento de pacientes con arritmiasventriculares y prevención de la muerte súbita cardiaca

Abstract: Los miembros del Comite de la ESC para la Elaboracion de GPC y los revisores del documento representantes de las sociedades nacionales de cardiologia aparecen listados en el apendice. Se puede consultar las declaraciones de conflicto de intereses de los expertos participantes en el desarrollo de esta guia en la pagina web de la ESC: www.escardio.org/guidelines

How Normal Is a ‘Normal' Heart in Fetuses and Infants with Down Syndrome?

Abstract: Background: Congenital heart disease is present in 44-56% of fetuses with Down syndrome (DS). There are, however, signs that hearts in DS without apparent structural heart defects also differ from those in the normal population. We aimed to compare the atrioventricular (AV) septum and valves in 3 groups: DS without AV septal defect (DS no-AVSD), DS with AVSD (DS AVSD) and control hearts. Methods: The ventricular septum, membranous septum and AV valves were examined and measured in histological sections of 15 DS no-AVSD, 8 DS AVSD and 34 control hearts. In addition, the ventricular septum length was measured on ultrasound images of fetal (6 DS AVSD, 9 controls) and infant (10 DS no-AVSD, 10 DS AVSD, 10 controls) hearts. Results: The membranous septum was 3 times larger in DS no-AVSD fetuses compared to control fetuses, and valve dysplasia was frequently (64%) observed. The ventricular septum was shorter in patients with DS both with and without AVSD, as compared to the control group. Conclusion: DS no-AVSD hearts are not normal as they have a larger membranous septum, shorter ventricular septum and dysplasia of the AV valves as compared to control hearts.

Chromosomal abnormalities and copy number variations in fetal left‐sided congenital heart defects

Abstract: Objectives To demonstrate the spectrum of copy number variants (CNVs) in fetuses with isolated left-sided congenital heart defects (CHDs), and analyse genetic content. Methods Between 2003 and 2012, 200 fetuses were identified with left-sided CHD. Exclusion criteria were chromosomal rearrangements, 22q11.2 microdeletion and/or extra-cardiac malformations (n = 64). We included cases with additional minor anomalies (n = 39), such as single umbilical artery. In 54 of 136 eligible cases, stored material was available for array analysis. CNVs were categorized as either (likely) benign, (likely) pathogenic or of unknown significance. Results In 18 of the 54 isolated left-sided CHDs we found 28 rare CNVs (prevalence 33%, average 1.6 CNV per person, size 10.6 kb–2.2 Mb). Our interpretation yielded clinically significant CNVs in two of 54 cases (4%) and variants of unknown significance in three other cases (6%). Conclusions In left-sided CHDs that appear isolated, with normal chromosome analysis and 22q11.2 FISH analysis, array analysis detects clinically significant CNVs. When counselling parents of a fetus with a left-sided CHD it must be taken into consideration that aside from the cardiac characteristics, the presence of extra-cardiac malformations and chromosomal abnormalities influence the treatment plan and prognosis. © 2015 John Wiley & Sons, Ltd.

Pregnancy complications in singleton pregnancies with isolated fetal heart defects

Abstract: Introduction As the prenatal detection rates of congenital heart defects (CHDs) increase, obstetricians are more frequently faced with pregnancies complicated by a fetal CHD. Congenital anomalies in general are associated with preterm birth and fetal demise. The aim of this study was to gain insight into the prevalence of preterm birth and fetal demise in singleton pregnancies with fetuses with isolated CHDs. Material and methods A geographical cohort study was performed in a large region in the Netherlands. Fetuses and infants from singleton pregnancies diagnosed with severe isolated CHD, born between 1 January 2002 and 1 January 2012, were included. All cases in the CHD cohort were assessed for preterm birth or fetal demise. The proportions of preterm birth and fetal demise were compared with those in a control group and odds ratios were calculated. Results The proportion of preterm births in the CHD cohort (n = 1013) was 9.1% (95% CI 7.3–10.9) compared with 5.6% (95% CI 5.4–5.8) in the control group, with an odds ratio of 1.7 (95% CI 1.4–2.1). The preterm birth started spontaneously in 49.5% and 38.4% were induced. In 15 cases fetal demise occurred (1.5%; 95% CI 0.8–2.2), compared with 0.7% (95% CI 0.6–0.8) in the control group, odds ratio 2.0 (95% CI 1.2–3.4). Conclusions Higher rates of preterm birth and fetal demise occur in fetuses with isolated CHD compared with the general population. Prenatal specialists should be vigilant for signs of heart failure, premature closure of the foramen ovale or fetal distress in fetuses with isolated CHDs.

KinCor, a national registry for paediatric patients with congenital and other types of heart disease in the Netherlands: aims, design and interim results

Abstract: Studies in children with heart disease have been hampered by a lack of easily identifiable patient groups. Currently, there are few prospective population-based registries covering the entire spectrum of heart disease in children. KinCor is a Dutch national registry for children with heart diseases. This paper presents the aims, design and interim results of the KinCor project. All children presenting at a Dutch university medical centre with a diagnosis of heart disease from 2012 onwards were eligible for registration in the KinCor database. Data entry is through a web-based portal. Entry codes have been synchronised with the European Paediatric Cardiac Coding system, allowing coupling with similar databases for adults, such as CONCOR. Between June 2012 and July 2015, 8421 patients were registered (76 % of those eligible). Median age of the patients was 9.8 years, 44.7 % were female; 6782 patients had morphological congenital heart disease. The most prevalent morphological congenital heart defects were ventricular septal defects (18 %), Tetralogy of Fallot (10 %) and transposition of great arteries (9 %). For 42 % of the patients additional diagnoses were registered. Sixty percent of patients had undergone at least one intervention (catheter intervention or surgery). The KinCor database has developed into a large registry of data of children with all types of heart disease and continues to grow. This database will provide the opportunity for epidemiological research projects on congenital and other types of heart disease in children. Entry codes are shared with the CONCOR database, which may provide a unique dataset.