Papers by Ingegerd Östman-Smith
Screening for congenital heart disease with newborn pulse oximetry
The Lancet, 2012
Screening for congenital heart disease with newborn pulse oximetry. By - Peter Macfarlane, Rupa T... more Screening for congenital heart disease with newborn pulse oximetry. By - Peter Macfarlane, Rupa Talekar.
American Journal of Perinatology, 2016
The detection of newborn babies with potentially life-threatening, critical congenital heart defe... more The detection of newborn babies with potentially life-threatening, critical congenital heart defects (CCHDs) before they collapse or expire remains an important clinical challenge. The absence of physical signs and the difficulty assessing mild cyanosis means that the newborn baby check misses up to a third of babies. Fetal anomaly ultrasound scanning identifies an increasing proportion, but this screen is operator-dependent and therefore highly variable; although some units report very high detection rates, overall most babies with CCHD are still missed. Pulse oximetry screening (POS) is an additional test that meets the criteria for universal screening. POS increases overall detection of CCHD to over 90% and also identifies babies with noncardiac, hypoxemic conditions (such as congenital pneumonia, early-onset sepsis, and pulmonary hypertension), which are usually included in the false positives. There is a wealth of published data on the POS, both in a research setting and more r...
Cochrane Database of Systematic Reviews, Apr 23, 2008
Study characteristics This review summarises and discusses the available information on the use o... more Study characteristics This review summarises and discusses the available information on the use of beta-blockers in children with congestive heart failure. Seven studies, with a total of 420 children were included in the review. Key results Beta-blocker therapy improved heart failure in four small studies with less than 30 participants each, and two larger studies with 80 participants each. However, the largest trial, with 161 participants, did not show a significant e ect of the investigated beta-blocker over placebo. None of the studies reported any severe beta-blocker-related adverse events, apart from one child who had a heart rhythm disturbance. Conclusions There were not enough data to recommend or discourage the use of beta-blockers in children with congestive heart failure. However, the current available data suggest that children with heart failure might benefit from beta-blocker treatment. Further investigations are required to establish guidelines for therapy. Beta-blockers for congestive heart failure in children (Review)
Genotype-phenotype correlations in hypertrophic cardiomyopathy can be confounded by double mutations in a single disease gene
Heart, May 1, 2000
Journal of Medical Genetics, Jun 1, 2001
T. A myosin missense mutation, not a null allele, causes familial hypertrophic cardiomyopathy.
P1245In a prospective randomized study in familial hypertrophic cardiomyopathy, metoprolol maintains exercise-performance, with lower myocardial oxygen-cost, and prevents deterioration in exercise-ability
European Heart Journal, Oct 1, 2019
Background Hypertrophic cardiomyopathy (HCM) is an inherited disorder with a prevalence of 0.2% i... more Background Hypertrophic cardiomyopathy (HCM) is an inherited disorder with a prevalence of 0.2% in young adults, with a significant risk of sudden death. Another feature of the disease is progressive fibrosis causing late heart failure. International guidelines suggest beta-blocker therapy for symptomatic patients, but that symptom-free patients need not be treated. Cohort studies on pediatric HCM-patients have suggested that beta-blocker therapy has a dose-related protective effect on the risk for sudden death, suggesting prophylactic beta-blocker therapy might benefit symptom-free patients. Purpose As prophylactic beta-blocker therapy is presumed to have a negative effect on exercise-ability, we assessed the effect of selective beta-blocker therapy on exercise hemodynamics and exercise performance in asymptomatic HCM patients. Methods Previously un-diagnosed cases of HCM were identified by family screening; those without symptoms and risk-factors were randomized to either life-style advice only (Obs-group; n=15), or to advice plus metoprolol therapy (Bbl-group; n=12). Patients performed bicycle ergometer testing before randomization, and yearly during follow-up. Performance in Watt was related to predicted normal for age, body size and sex; heart rate and blood pressure was recorded every minute during exercise terminated by patient tolerance. Results Median age was 18 [IQR 14–26]yrs, with a median follow-up of 6.0 [2.0–8.0]yrs. In the Obs-group the exercise-ability had deteriorated after two years (median 80% predicted vs. initial 88%, p=0.021), and remained lower at last follow-up, 78% (p=0.0017). Patients in the Bbl-group received a median final dose of 325mg metoprolol/day, corresponding to 3.8 [3.5–4.3]mg/kg, and had a reduction in maximal heart rate, 134 vs. 182 bpm (p=0.ehz748.02033], and systolic blood pressure 164 vs. 182 mmHg (p=0.0077), at maximal work load compared to Obs-group. In spite of reduction in maximal heart rate there was no reduction in maximal work capacity in Bbl-group (p=0.33 two year, p=0.50 last follow-up), with within patient change 2% of predicted [−3 to +5]% vs. −6% [−14 to −3]% in Obs-group (p=0.0039). Last visit work capacity was 180 [170–190]Watt in Obs-group and 205 [185–210]Watt in Bbl-group (p=0.015). Rate-pressure product (RPP) was 29% lower, and Watt/RPP was improved by 42% in Bbl-group compared to Obs-group (0.0084 vs. 0.0059; p=0.ehz748.02032). Conclusions Untreated patients with asymptomatic HCM show a slow deterioration in exercise-ability over follow-up, whereas patients treated with metoprolol do not decrease exercise performance compared with pre-treatment values, and do not deteriorate on medium-term follow-up. As myocardial oxygen consumption is linearly related to RPP, Bbl-group achieves a good exercise performance with substantially lower myocardial oxygen consumption than the Obs-group, which may have relevance for subendocardial ischaemia on exercise and future development of myocardial fibrosis. Acknowledgement/Funding Swedish Heart-Lung Fundation grant nr 20080510, Gothenburg University ALF grant nr ALFgbg-544981
[Sympathomimetics in ADHD. Cardiovascular risks, FDA warns]
PubMed, Jun 6, 2007
Open access journal of sports medicine, Jul 1, 2011
Athletic activity is associated with an increased risk of sudden death for individuals with some ... more Athletic activity is associated with an increased risk of sudden death for individuals with some congenital or acquired heart disorders. This review considers in particular the causes of death affecting athletes below 35 years of age. In this age group the largest proportion of deaths are caused by diseases with autosomal dominant inheritance such as hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, long QT-syndrome, and Marfan's syndrome. A policy of early cascade-screening of all first-degree relatives of patients with these disorders will therefore detect a substantial number of individuals at risk. A strictly regulated system with preparticipation screening of all athletes following a protocol pioneered in Italy, including school-age children, can also detect cases caused by sporadic new mutations and has been shown to reduce excess mortality among athletes substantially. Recommendations for screening procedure are reviewed. It is concluded that ECG screening ought to be part of preparticipation screening, but using criteria that do not cause too many false positives among athletes. One such suggested protocol will show positive in approximately 5% of screened individuals, among whom many will be screened for these diseases. On this point further research is needed to define what kind of false-positive and false-negative rate these new criteria result in. A less formal system based on cascade-screening of relatives, education of coaches about suspicious symptoms, and preparticipation questionnaires used by athletic clubs, has been associated over time with a sizeable reduction in sudden cardiac deaths among Swedish athletes, and thus appears to be worth implementing even for junior athletes not recommended for formal preparticipation screening. It is strongly argued that in families with autosomal dominant disorders the first screening of children should be carried out no later than 6 to 7 years of age.
International Journal of Cardiology, Oct 1, 2013
Östman-Smith I. A study of the physiological consequences of sympathetic denervation of the heart... more Östman-Smith I. A study of the physiological consequences of sympathetic denervation of the heart caused by the arterial switch procedure.
Journal of Medical Genetics, 2001
Familial hypertrophic cardiomyopathy (HCM) has been widely studied as a genetic model of cardiac ... more Familial hypertrophic cardiomyopathy (HCM) has been widely studied as a genetic model of cardiac hypertrophy and sudden cardiac death. HCM has been defined as a disease of the cardiac sarcomere, but mutations in the known contractile protein disease genes are not found in up to one-third of cases. Further, no consistent changes in contractile properties are shared by these mutant proteins, implying that an abnormality of force generation may not be the underlying mechanism of disease. Instead, all of the sarcomeric mutations appear to result in inefficient use of ATP, suggesting that an inability to maintain normal ATP levels may be the central abnormality. To test this hypothesis we have examined candidate genes involved in energy homeostasis in the heart. We now describe mutations in PRKAG2, encoding the γ 2 subunit of AMP-activated protein kinase (AMPK), in two families with severe HCM and aberrant conduction from atria to ventricles in some affected individuals (pre-excitation or Wolff-Parkinson-White syndrome). The mutations, one missense and one in-frame single codon insertion, occur in highly conserved regions. Because AMPK provides a central sensing mechanism that protects cells from exhaustion of ATP supplies, we propose that these data substantiate energy compromise as a unifying pathogenic mechanism in all forms of HCM. This conclusion should radically redirect thinking about this disorder and also, by establishing energy depletion as a cause of myocardial dysfunction, should be relevant to the acquired forms of heart muscle disease that HCM models.
British Journal of Pharmacology, Nov 1, 1995
Studies on cardiac myocyte cell cultures have postulated a role for a1-adrenoceptors and mechanic... more Studies on cardiac myocyte cell cultures have postulated a role for a1-adrenoceptors and mechanical stretch in the induction of cellular changes thought to be important in compensatory cardiac hypertrophy. However, in vivo work suggests that fi-adrenoceptors are important and the present study was designed to analyse the effect of propranolol on the cardiac hypertrophy caused by a pressureoverload in a way that takes account of the effects of propranolol on the work load itself. 2 The compensatory cardiac hypertrophy that develops in response to experimental coarctation of the aorta was studied in the rat. Pressure gradients and total cardiac work load (expressed as rate x pressure product) were assessed, and the relationship between increasing cardiac work load and the resulting left ventricular hypertrophy was established in a control group and compared with left ventricular hypertrophy in a group treated with a high dose of oral propranolol (80 mg kg-' body weight). 3 In the rats with mean pressure gradients over the coarctation in the range of 15-31 mmHg, the animals on control diet showed a 38% increase in left ventricular weight/body weight ratio (LV ratio) and a 30% increase in heart weight/body weight ratio (heart ratio), whereas rats given high dose oral propranolol-treatment showed increases of only 13% and 9%, respectively. 4 In a second series of rats with a wider range of pressure gradients, the regression lines of LV ratio versus mean pressure gradient, and of LV ratio versus cardiac work, were different in the two groups with a slope that was only half as steep in the propranolol-treated rats as in the controls. Thus, for the same increment in cardiac work load, the degree of compensatory cardiac hypertrophy in propranololtreated rats was half that observed in controls. 5 The reduction in compensatory cardiac hypertrophy was not associated with an increase in incidence of congestive heart failure and the propranolol-treated rats were able to sustain equally high (or higher) degrees of pressure overload as controls did. 6 It is concluded that propranolol treatment approximately halves the compensatory cardiac hypertrophy occurring in response to a left ventricular pressure overload by a mechanism indepenent of its effect on cardiac work load. This finding provides further support for the view that noradrenaline released from sympathetic nerve terminals in the heart exerts a trophic effect on cardiac myocytes, and that the sympathetic nervous system may be the final common pathway in many forms of compensatory cardiac hypertrophy.
Adaptive changes in the sympathetic nervous system and some effector organs of the rat following long term exercise or cold acclimation and the role of cardiac sympathetic nerves in the genesis of compensatory cardiac hypertrophy
PubMed, 1979
Differentiation of Athlete's Heart from Pathological Forms of Cardiac Hypertrophy by Means of Geometric Indices Derived from Cardiovascular Magnetic Resonance
Journal of Cardiovascular Magnetic Resonance, May 1, 2005
Heart Lung and Circulation, 2014
Background: Two-pore domain K + (K 2 P) channels are key determinants of background K + conductan... more Background: Two-pore domain K + (K 2 P) channels are key determinants of background K + conductance in cardiomyocytes, providing dynamic regulation of cellular membrane potential. As these channels are highly expressed and functionally active in human atria they may play a role in the pathogenesis of atrial fibrillation and could be novel drug targets. We have recently shown that genetic alterations in a member of the K 2 P family, TASK-1, cause atrial remodeling and electrophysiological abnormalities. However, very little is known about another K 2 P channel, TWIK-1. Methods and Results: We initially evaluated the loss of TWIK-1 function in vivo utilising a zebrafish model. Individual morpholino-mediated knockdown of the two zebrafish TWIK-1 orthologues, kcnk1a and kcnk1b, resulted in atrial dilation and bradycardia by 72 hours post fertilisation, which were aggravated when both genes were targeted simultanously (all p < 0.05). Subsequent genetic screening of KCNK1 in 165 unrelated human probands with familial atrial fibrillation resulted in the identification of 3 gene variants of interest; one common variant (p.R171H) significantly overrepresented in affected vs unaffected individuals, one rare (p.G236S), and one novel variant (p.I198M). Electrophysiological evaluation of these variants is ongoing. Conclusion: Our in vivo findings demonstrate the importance of TWIK-1 in the function and development of the atrium and the conduction system. Our mutation screening suggests that genetic variants in TWIK-1 may contribute to atrial arrhythmogenesis.
International Journal of Cardiology, 2021
Background: Treatment of left ventricular outflow-obstruction (LVOTO) in hypertrophic obstructive... more Background: Treatment of left ventricular outflow-obstruction (LVOTO) in hypertrophic obstructive cardiomyopathy (HOCM) by short atrio-ventricular delay pacing has long-term hemodynamic results that are not inferior to myectomy, but publications comparing long-term morbidity following those treatments are lacking. Methods: A search for HOCM-patients attending all ten hospitals in the West Götaland Region, Sweden, from 2002 through 2013, identified 251 patients (42 treated with myectomy, 88 with pacing and 121 conservatively). As the age at procedure was significantly lower in the myectomy-group compared to the pacing-group, morbidity was compared by case-control methodology, matching patients for age, maximal wall thickness and LVOTgradient. We found 31 pairs who constituted the comparison-groups. Post-intervention median follow-up was 15.4 and 10.4 years in pacing-and myectomy-group, respectively. Post-procedural and long-term complications and re-interventions, length of stay, and cost of hospitalization were documented. Results: Both treatments improved New York Heart Association class and LVOT-gradients significantly. There were fewer peri-procedural complications in the pacing-group compared to myectomy-group (3.2% and 35.5% p < 0.001). During follow-up pacemaker was implanted in 35.5% of myectomy-group for atrio-ventricular block, 9.7% peri-operatively, and 25.8% during late-follow-up. Furthermore, the pacing group had a superior freedom from all re-interventions, 90.3% versus 61.3% in myectomy-group (p = 0.003). Pacing patients had a shorter in-hospital stay (median 4 [IQR = 2] days) compared to myectomy 11 [7] days; P < 0.001). The mean cost of hospitalization was 74,000 ± 16,000 SEK for pacing and 310,000 ± 180,000 SEK for myectomy, p < 0.001. Conclusion: Pacing is a simple and reliable treatment for drug-refractory HOCM-patients with low rate of complications and costs.
Difficulties in diagnosing acute rheumatic fever-arthritis may be short lived and carditis silent
BMJ, Feb 5, 2000
European Journal of Obstetrics & Gynecology and Reproductive Biology, Nov 1, 1991
A 32-year-old woman with systemic lupus erythematosus was found to have a fetus with heart block ... more A 32-year-old woman with systemic lupus erythematosus was found to have a fetus with heart block and fetal ascites at 23 weeks gestation. Treatment with high-dose corticosteroids ameliorated the early signs of heart failure, although the fetal heart rate gradually fell from 48 beats/min to 42 beats/min by 34 weeks. Sudden deterioration of the fetal state occurred at 35 weeks, and this only partially responded to digitalisation. Neonatal death occurred on Day 18 from the consequences of severe birth asphyxia. The relationship and pathogenesis of anti-R0 antibodies, congenital heart block and hydrops fetals are discussed, together with the in utero management of this condition.
Open heart, Jun 1, 2019
Factors influencing long-term heart failure mortality in patients with obstructive hypertrophic c... more Factors influencing long-term heart failure mortality in patients with obstructive hypertrophic cardiomyopathy in Western Sweden: probable dose-related protection from beta-blocker therapy.
Cardiology in The Young, Nov 1, 2000
The aims of these recommendations are to improve the outcome for patients after, and to provide a... more The aims of these recommendations are to improve the outcome for patients after, and to provide acceptable standards of practice of, therapeutic cardiac catheterisation performed to treat congenital cardiac disease. The scope of the recommendations includes all interventional procedures, recognising that for some congenital malformations, surgical treatment is equally as effective as, or occasionally preferable to, interventional treatment. The limitations of the recommendations are that, at present, no data are available which compare the results of interventional treatment with surgery, and certainly none which evaluate the numbers and types of procedures that need to be performed for the maintenance of skills. Thus, there is a recognised need to collect comprehensive data with which these recommendations could be reviewed in the future, and rewritten as evidence-based guidelines. Such a review will have to take into account the methods of collection of data, their effectiveness, and the latest developments in technology. The present recommendations should, therefore, be considered as consensus statements, and as describing accepted practice, which could be used as a basis for ensuring and improving the quality of future care. D URING THE LAST FIFTEEN YEARS, MAJOR developments have occurred in the use of interventional techniques in paediatric cardiology. 1 " 6 During the same period, advances have also occurred in the imaging of congenital cardiac malformations which have rationalised the indications for diagnostic cardiac catheterisation, leading to more selective use of diagnostic procedures in the catheterisation theatres. Most of the anatomical information required for making decisions on treatment can now be obtained by crosssectional and colour Doppler echocardiography.
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Papers by Ingegerd Östman-Smith