Adult congenital heart disease training in Europe: current status, disparities and potential solutions.

OBJECTIVES: This study aimed to determine the status of training of adult congenital heart disease (ACHD) cardiologists in Europe. METHODS: A questionnaire was sent to ACHD cardiologists from 34 European countries. RESULTS: Representatives from 31 of 34 countries (91%) responded. ACHD cardiology was recognised by the respective ministry of Health in two countries (7%) as a subspecialty. Two countries (7%) have formally recognised ACHD training programmes, 15 (48%) have informal (neither accredited nor certified) training and 14 (45%) have very limited or no programme. Twenty-five countries (81%) described training ACHD doctors 'on the job'. The median number of ACHD centres per country was 4 (range 0-28), median number of ACHD surgical centres was 3 (0-26) and the median number of ACHD training centres was 2 (range 0-28). An established exit examination in ACHD was conducted in only one country (3%) and formal certification provided by two countries (7%). ACHD cardiologist number versus gross domestic product Pearson correlation coefficient=0.789 (p<0.001). CONCLUSION: Formal or accredited training in ACHD is rare among European countries. Many countries have very limited or no training and resort to 'train people on the job'. Few countries provide either an exit examination or certification. Efforts to harmonise training and establish standards in exit examination and certification may improve training and consequently promote the alignment of high-quality patient care.

Paediatric and adult congenital cardiology education and training in Europe.

BACKGROUND: Limited data exist on training of European paediatric and adult congenital cardiologists. METHODS: A structured and approved questionnaire was circulated to national delegates of Association for European Paediatric and Congenital Cardiology in 33 European countries. RESULTS: Delegates from 30 countries (91%) responded. Paediatric cardiology was not recognised as a distinct speciality by the respective ministry of Health in seven countries (23%). Twenty countries (67%) have formally accredited paediatric cardiology training programmes, seven (23%) have substantial informal (not accredited or certified) training, and three (10%) have very limited or no programme. Twenty-two countries have a curriculum. Twelve countries have a national training director. There was one paediatric cardiology centre per 2.66 million population (range 0.87-9.64 million), one cardiac surgical centre per 4.73 million population (range 1.63-10.72 million), and one training centre per 4.29 million population (range 1.63-10.72 million population). The median number of paediatric cardiology fellows per training programme was 4 (range 1-17), and duration of training was 3 years (range 2-5 years). An exit examination in paediatric cardiology was conducted in 16 countries (53%) and certification provided by 20 countries (67%). Paediatric cardiologist number is affected by gross domestic product (R2 = 0.41). CONCLUSION: Training varies markedly across European countries. Although formal fellowship programmes exist in many countries, several countries have informal training or no training. Only a minority of countries provide both exit examination and certification. Harmonisation of training and standardisation of exit examination and certification could reduce variation in training thereby promoting high-quality care by European congenital cardiologists.

Sequence variants with large effects on cardiac electrophysiology and disease.

Features of the QRS complex of the electrocardiogram, reflecting ventricular depolarisation, associate with various physiologic functions and several pathologic conditions. We test 32.5 million variants for association with ten measures of the QRS complex in 12 leads, using 405,732 electrocardiograms from 81,192 Icelanders. We identify 190 associations at 130 loci, the majority of which have not been reported before, including associations with 21 rare or low-frequency coding variants. Assessment of genes expressed in the heart yields an additional 13 rare QRS coding variants at 12 loci. We find 51 unreported associations between the QRS variants and echocardiographic traits and cardiovascular diseases, including atrial fibrillation, complete AV block, heart failure and supraventricular tachycardia. We demonstrate the advantage of in-depth analysis of the QRS complex in conjunction with other cardiovascular phenotypes to enhance our understanding of the genetic basis of myocardial mass, cardiac conduction and disease.

Variants in NKX2-5 and FLNC Cause Dilated Cardiomyopathy and Sudden Cardiac Death.

BACKGROUND: Dilated cardiomyopathy (DCM) is an important cause of heart failure. Variants in >50 genes have been reported to cause DCM, but causative variants have been found in less than half of familial cases. Variants causing DCM in Iceland have not been reported before. METHODS: We performed a genome-wide association study on DCM based on whole genome sequencing. We tested the association of 32.5 million sequence variants in 424 cases and 337 689 population controls in Iceland. RESULTS: We identified 2 DCM variants in established cardiomyopathy genes, a missense variant p.Phe145Leu in NKX2-5 carried by 1 in 7100 Icelanders ( P=7.0×10-12) and a frameshift variant p.Phe1626Serfs*40 in FLNC carried by 1 in 3600 Icelanders ( P=2.1×10-10). Both variants associate with heart failure and sudden cardiac death. Additionally, p.Phe145Leu in NKX2-5 associates with high degree atrioventricular block and atrial septal defect ( P<1.4×10-4). The penetrance of serious heart disease among carriers of the NKX2-5 variant is high and higher than that of the FLNC variant. CONCLUSIONS: Two rare variants in NKX2-5 and FLNC, carried by 1 in 2400 Icelanders, cause familial DCM in Iceland. These genes have recently been associated with DCM. Given the serious consequences of these variants, we suggest screening for them in individuals with DCM and their family members, with subsequent monitoring of carriers, offering early intervention.

Genome-wide analysis yields new loci associating with aortic valve stenosis.

Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10-22) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10-13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10-10) and aortic root diameter (P = 1.30 × 10-8), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10-3) and coronary artery disease (OR = 1.05, P = 9.3 × 10-5). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.

Nordic pulse oximetry screening--implementation status and proposal for uniform guidelines.

AIM: Pulse oximetry screening of newborn infants increases early detection of critical congenital heart disease and minimises the risk of circulatory collapse before surgery. This study provides an update on the implementation of pulse oximetry screening in the Nordic countries and proposes standardised guidelines. METHODS: A questionnaire exploring pulse oximetry screening, clinical examination routines and availability of echocardiography was distributed to all 157 delivery units in the Nordic countries in June 2013. RESULTS: We received responses from 156 of the 157 delivery units, and 116 (74%) were using pulse oximetry screening by September 2013. Preductal and postductal screening were both used in 59 of 116 units (51%), with just postductal screening in 51 of 116 (44%) and just preductal screening alone in 6 of 116 (5%). Screening was performed before 24 h in 105 of 116 units (91%). The implementation of screening was highest in Finland (29/30, 97%), Sweden (42/46, 91%) and Norway (43/48, 90%) and lowest in Denmark (2/24, 8%) and Iceland (0/8 units). CONCLUSION: In Sweden, Norway and Finland, the implementation of pulse oximetry screening is currently the highest in the world and coverage will be close to 100% in 2014. We propose uniform Nordic guidelines using preductal and postductal screening before 24 h of age.

[Cardiac arrest in a teenager - a case report]. / Hjartastopp hja unglingsstulku - sjukratilfelli.

Cardiac arrest is rarely seen in children and teenagers. We present a 12-year old girl with cardiac arrest following myocardial infarction, that required prolonged cardiac massage and extracorporeal-membranous-oxygenation (ECMO). At coronary angiography the left main coronary artery (LMCA) was stented for a suspected coronary dissection. The contraction of the heart improved and the ECMO-treatment was discontinued a week later. The patient was discharged home, but six months later a coronary artery bypass surgery was performed for in-stent restenosis. Further work-up with computed tomography (CT) showed that the LMCA originated from the right aortic sinus instead of the the left one. This case demonstrates how life threatening myocardial infarction can be caused by coronary artery anomalies.

[Kawasaki disease in Iceland 1996-2005, epidemiology and complications]. / Kawasaki-sjúkdómur á Íslandi 1996-2005, faraldsfrædi og fylgikvillar.

OBJECTIVE: To analyze the epidemiology of Kawasaki disease in Icelandic children and its complications. METHODS: A retrospective analysis of all cases of Kawasaki disease and atypical Kawasaki disease in children in Iceland from 1996-2005. Chart records were reviewed and children diagnosed at Landspítali - University Hospital invited for a Follow up study with emphasis on heart complications. RESULTS: Thirty children were diagnosed with Kawasaki disease, annual incidence was 10.7/100.000 children <5 years of age. The boy:girl ratio was 2.3:1. All 30 children were treated with IVIG, without any major adverse events related to the treatment. The median time from the initial symptoms to treatment was six days (range 3-31 days). There was no mortality. Two children developed coronary aneurysms and three coronary ectasia. Follow up echocardiography was preformed in 23 of the children four to twelve years after Kawasaki disease. Two of the children still had coronary ectasia, and six (26%) had mitral regurgitation. CONCLUSIONS: The incidence of Kawasaki disease in Iceland was comparable to an earlier Icelandic study and reported incidence in the Nordic countries. Coronary involvement during the acute phase was mild, and all coronary aneurysm regressed. Serious cardiac complications were not seen. Children with Kawasaki disease in Iceland have favorable prognosis. Interestingly, mild mitral regurgitation and coronary ectasia were common at mid-term follow up.

[Fetal echocardiography in Iceland 2003-2007; indications and outcomes]. / Fósturhjartaómskodanir á Islandi 2003-2007; ábendingar og útkoma.

OBJECTIVE: The aim of the study was to evaluate the indications and outcomes of fetal echo (FE) and determine which indication has the highest detection rate for congenital heart disease (CHD). METHODS: The referral indications and results of FE performed in Iceland during 2003-2007 were reviewed. Information regarding gestational age at diagnosis, nuchal translucency, pregnancy outcome, autopsy results and postnatal diagnosis were obtained from medical records. RESULTS: During the five year period 1187 FE were performed. Structural heart defect was diagnosed in 73 fetuses. The most common referral indication was family history of CHD (631;53.2%) which led to diagnosis of 18 heart defects prenatally (2.9%). The second most common referral indication was increased nuchal translucency (159) and abnormal cardiac findings were present in 16 cases (10.1%). A total of 30 women were referred for FE because of abnormal four chamber view (AFCV) which resulted in the diagnosis of 22 (73.3%) major heart defects, either incompatible with life or requiring immediate intervention after birth. Other indications led mostly to the diagnoses of minor defects. CONCLUSIONS: AFCV is the most important predictor for diagnosis of structural heart defects. 2,5% were referred for FE due to AFCV which led to diagnosis of 30% of all heart defects, all of which were major. Key words: fetal echocardiography, indications, congenital heart disease.

Acute decrease of coronary flow after indomethacin delivery in newborn lambs.

AIM: To document the effects of indomethacin (IND) on coronary flow. METHODS: We studied nine premature lambs during the first day of life. The gestational age varied between 132 and 134 days (term 145 days) and weight 3.1-4.7 kg. Coronary flow velocities were recorded with an intracoronary Doppler guide wire in the proximal left anterior descending coronary artery (LAD). Average peak flow velocity was measured before, during and after an intravenous IND injection of 0.2 mg per kilogram of body weight. RESULTS: IND increased systemic blood pressure (p < 0.05) and rate pressure product (RPP; p < 0.05) indicating that IND increased cardiac workload. IND decreased coronary average peak flow velocity in all lambs (p < 0.05). The maximal fall in coronary velocity appeared after 3 min (range 1-7 min) and was regained 10 min (range 4-53 min) after the drug delivery. The maximal reduction of coronary average peak flow velocity was 52% (median 26). The recovery time was directly related to the maximal reduction of the coronary average peak flow velocity (R = 0.91, R(2) 0.84, p < 0.002). CONCLUSION: Coronary flow velocity decreased markedly in premature born lambs given a bolus dose of IND.

Perinatal adaptive response of the adrenal and carotid blood flow in sheep fetuses subjected to total cord occlusion.

OBJECTIVE: To investigate the perinatal adaptive response of the adrenal blood flow/adrenal fractional moving blood volume (AFMBV) and carotid blood flow (CBF), in sheep fetuses subjected to severe acute intrauterine hypoxia/asphyxia induced by total cord occlusion. METHODS: Adrenal blood flow velocity, AFMBV and CBF were measured in 13 exteriorized fetal sheep; eight of them underwent total umbilical cord occlusion to induce severe acute hypoxia/asphyxia. Five lambs were used as sham controls. Middle adrenal artery pulsatility index (MAAPI) and mean velocity (MAAMV) were recorded with pulsed Doppler ultrasound. AFMBV was estimated using power Doppler ultrasound. CBF was recorded with a transonic flowmeter. In the neonatal period, after resuscitation all lambs were followed for a 4-hour period and AFMBV and CBF were recorded. Mean arterial blood pressure (MABP) and fetal heart rate were recorded continuously. Arterial cortisol levels were measured at the beginning and at the end of the fetal and neonatal periods. RESULTS: Following the total cord occlusion, there was a significant reduction in the CBF, MABP, and heart rate and adrenal flow/AFMBV after 2, 4 and 5 min, respectively. Cortisol levels in the asphyctic lambs at the end of the cord occlusion were significantly lower than those in controls. After resuscitation, the asphyctic lambs showed increased AFMBV and cortisol levels, and reduced MABP as compared to control lambs. No differences were found in CBF, MAAPI and MAAMV. Thereafter, no differences were observed between the two groups in any of the studied parameters. At the end of the cord occlusion period, there was a significant correlation between AFMBV and MABP (r=0.69), between AFMBV and CBF (r =0.65) and between CBF and MABP (r=0.89). CONCLUSION: During severe acute intrauterine hypoxia, the fetal lamb is able to maintain the blood flow to the brain and the adrenal gland for 3-5 min. Changes in the AFMBV and the CBF were highly correlated to the changes in MABP. Adrenal FMBV and cortisol levels were higher in lamb neonates exposed to severe intrauterine asphyxia.

Different responses of myocardial and cerebral blood flow to cord occlusion in exteriorized fetal sheep.

Type and duration of fetal asphyxial insult affect the distribution of blood flow to the heart and brain. The purpose of this study was to describe dynamic and quantitative changes in regional myocardial and cerebral blood flow (CBF) during fetal asphyxia induced by total occlusion of the umbilical cord. Eleven exteriorized fetal sheep were subjected to total umbilical cord occlusion and five fetal sheep served as sham controls. Regional blood flow (BF) to the brain and heart was quantified using radioactive microspheres before and after 5 min of occlusion and finally when fetal mean arterial blood pressure had decreased below 25 mm Hg, 9.8 (0.8) [mean (SD)] min after occlusion. Right coronary arterial (RCA) blood flow velocity and carotid BF were registered continuously. Mean values of arterial pH and oxygen content (mL O(2)/100 mL) were 7.08 (0.11) and 4.4 (2.9) before cord occlusion and decreased to 6.83 (0.05) and 1.4 (0.9) at 5 min after occlusion (p < 0.01, respectively). Carotid BF was significantly below preocclusion values by 2.5 min (p < 0.05), whereas RCA velocity time integral per minute remained above preocclusion values for 9 min. CBF decreased from 316 (24) before cord occlusion to 156 (30) mL/min/100 g at 5 min (p < 0.01), whereas right myocardial BF was maintained at 792 (125) and 751 (183) mL/min/100 g, respectively. CBF decreased rapidly after total cord occlusion whereas myocardial BF increased and was maintained until shortly before cardiac arrest, suggesting the myocardium to be better preserved during this type of insult in already partially asphyxiated fetuses.

Coronary flow reserve in the newborn lamb: an intracoronary Doppler guide wire study.

Recent studies indicate a severely reduced coronary flow reserve (CFR) in neonates with congenital heart disease. The significance of these studies remains debatable, as the ability of the anatomically normal neonatal heart to increase coronary flow is currently unknown. This study was designed to establish normal values for CFR in newborns after administration of adenosine [pharmacologic CFR (pCFR)] and as induced by acute hypoxemia (reactive CFR). Thirteen mechanically ventilated newborn lambs were studied. Coronary flow velocities were measured in the proximal left anterior descending coronary artery before and after adenosine injection (140 and 280 microg/kg i.v.) using an intracoronary 0.014-in Doppler flow-wire. Measurements were made at normal oxygen saturation (SaO(2)) and during progressive hypoxemia induced by lowering the fraction of inspired oxygen. CFR was defined as the ratio of hyperemic to basal average peak flow velocity. In a hemodynamically stable situation with normal SaO(2), pCFR was 3.0 +/- 0.5. pCFR decreased with increasing hypoxemia. Regression analysis showed a linear relation between SaO(2) and pCFR (R = 0.86, p < 0.0001). Reactive CFR obtained at severe hypoxemia (Sao(2) <30%) was 4.2 +/- 0.8, and no significant further increase in coronary flow velocity occurred by administration of adenosine. Newborn lambs have a similar capacity to increase coronary flow in response to both pharmacologic and reactive stimuli as older subjects. Administration of adenosine does not reveal the full capacity of the newborn coronary circulation to increase flow, however, as the flow increase caused by severe hypoxemia is significantly more pronounced.

Normal coronary flow reserve after arterial switch operation for transposition of the great arteries: an intracoronary Doppler guidewire study.

BACKGROUND: Recent studies performed with positron emission tomography have suggested that coronary flow reserve (CFR) is moderately to severely reduced after the arterial switch operation (ASO). These findings are of great concern but have not been confirmed by other methods. METHODS AND RESULTS: Eleven symptom-free children were studied between 4 and 11 (median 6.0) years after the ASO. Flow velocity in the left anterior descending (LAD) and right coronary arteries (RCA) was measured with a 0.014-inch Doppler FloWire (Cardiometrics) before and after intracoronary injection of adenosine (0.5 microg/kg) and nitroglycerin (5 microg/kg). CFR was defined as the ratio of hyperemic to basal average peak velocity (APV). The median (range) CFR in the LAD was 3.7 (3.0 to 4.8) and 3.4 (2.9 to 4.8) in the RCA. The increase in APV after intracoronary injection of nitroglycerin was 300% (240% to 420%) in the LAD and 260% (190% to 460%) in the RCA. APV at rest was 15.0 (14.0 to 21.0) cm/s in the LAD and 16.0 (9.6 to 30.0) cm/s in the RCA. A linear relation was found between right ventricular systolic pressure and resting APV in the RCA (r=0.77, P=0.0056), and between resting APV and CFR (r=-0.61, P<0.05) in the RCA. CONCLUSIONS: The CFR and coronary vasoreactivity to nitroglycerin in children treated for transposition of the great arteries with the ASO was within normal limits. Increased right ventricular pressure and myocardial hypertrophy can cause increased resting coronary flow velocity in the RCA and affect CFR negatively.