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

Peer reviewe

Sequence variants with large effects on cardiac electrophysiology and disease.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadFeatures 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

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

Doppler evaluation of coronary blood flow and coronary flow reserve - Clinical and experimental studies

Heart diseases in children cause different combinations of myocardial hypertrophy, increased intra-ventricular pressures, volume overload and decreased oxygen saturation. This may affect basal coronary flow and the ability of the heart to maximally increase coronary flow. Transthoracic and intracoronary Doppler techniques were used to register coronary flow and coronary flow reserve (CFR) in normal subjects and in children with heart disease. The same methods were employed in experimental studies (lamb model) where CFR in the newborn was defined, and the effects of fetal asphyxia on coronary flow as compared with cerebral flow were described. Flow velocity parameters and flow volume in the left anterior descending (LAD) coronary artery in healthy neonates and infants increase with age and left ventricular mass, and are affected by both systolic and diastolic left ventricular function. In neonates with severe aortic stenosis, systolic flow reversal and increased diastolic flow velocity were observed preoperatively, but the flow normalised immediately after operation. In infants with idiopathic idiopathic dilated cardiomyopathy, all LAD flow velocity parameters and flow volume were increased compared to age matched controls, while LAD flow corrected for left ventricular mass was reduced. Children treated with arterial switch operation for transposition of the great arteries who had normal postoperative hemodynamics had normal CFR in both the LAD and the right coronary artery (RCA). However, if residual lesions causing myocardial hypertrophy were present, the basal RCA flow velocity was increased and CFR reduced. CFR in the LAD in the newborn lamb, as measured by administration of adenosine, was found to be slightly lower (3.0) than what has been reported for older subject, while the reactive CFR, the flow response to rapid severe hypoxemia, was found to be significantly higher or 4.2. The circulatory response to fetal asphyxia was characterised by a rapid short-lived 4-fold increase in RCA flow, while cerebral blood flow decreased immediately. Doppler techniques can be used to describe the effects of heart disease and abnormal hemodynamic conditions on coronary flow and CFR in children. Abnormal coronary flow dynamics and reduced CFR may be associated with increased risk of myocardial ischemia, and these concepts may aid in decision-making regarding surgical and medical treatment of children with heart disease

Coronary flow and flow reserve in children

Aortic blood pressure affects coronary blood flow, but within the normal physiological blood pressure range coronary blood flow is constant. The coronary flow is pulsatile, being maximal in the early diastole. There is a smaller systolic flow component. The low systolic pressure in the right ventricle favours systolic flow. The proportion of systolic flow is greater in the right than in the left coronary artery. Heart diseases in children cause several haemodynamic and functional changes that are likely to affect myocardial perfusion. Newborns with severe valvular aortic stenosis may have a retrograde systolic flow in the left coronary artery. Children with dilated cardiomyopathy have a reduced coronary flow related to myocardial mass. Coronary flow reserve (CFR) is defined as the ratio of maximal coronary blood flow, as induced by reactive hyperaemia or administration of vasodilators, divided by resting flow. Coronary flow can normally increase 2.5-4-fold. CFR is reduced if basal flow is increased due to myocardial hypertrophy, strain or hypoxaemia. Very low CFR values measured with positron emission tomography are reported in neonates with surgically treated congenital heart disease. Measurement of coronary flow velocity with the intracoronary Doppler guide wire may be regarded as a reference or "gold standard" in the evaluation of coronary flow velocity and CFR. Conclusions: Coronary flow and CFR in children is a largely unexploited field, and has vast potential for future research

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

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 micro g/kg) and nitroglycerin (5 micro g/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

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

Reduced postnatal cerebral glucose metabolism measured by PET after asphyxia in near term fetal lambs

The effects of fetal asphyxia on cerebral function and development, involve the transition from fetal to neonatal life. Changes in cerebral glucose metabolism may be an early postnatal indicator of fetal asphyxia. The objective is to develop an experimental lamb model involving the transition from fetal to neonatal life and to examine the effect of fetal asphyxia with cerebral hypoxic ischemia on early postnatal cerebral glucose metabolism. Fetal asphyxia was induced by total umbilical cord occlusion in eight near-term fetal lambs (134-138 days) with the ewe under isoflurane-opiate anesthesia. The mean occlusion time until cardiac arrest was 14.5 (4.2) min (SD). Lambs were immediately delivered and standardized resuscitation was instituted after 2 min asystole. At 4 hr postnatal age, [18-F]Fluoro-2-deoxy-glucose (18-FDG) was injected intravenously in eight asphyxiated lambs and in eight controls. Cerebral glucose metabolism was examined by positron emission tomography (PET). As a result the mean arterial blood pressure, acid-base values, blood glucose and serum lactate at 4 hr postnatal age did not differ significantly between lambs subjected to umbilical cord occlusion and controls. EEG was abnormal in all lambs subjected to cord occlusion and normal in the controls at 4 hr postnatal age. Global cerebral metabolic rate (CMRgl) as determined by PET was significantly lower in lambs subjected to cord occlusion mean/median (SD) 22.2/19.6 (8.4) micromol/min/100 g) than in controls mean/median (SD) 37.8/35.9 (6.1); P < 0.01). Global CMRgl is significantly reduced in newborn lambs 4 hr after fetal asphyxia induced by umbilical cord occlusion. A reduction in CMRgl is an early indicator of global hypoxic cerebral ischemia