Publications by authors named "Brage H Amundsen"

35 Publications

Rationale for the ASSAIL-MI-trial: a randomised controlled trial designed to assess the effect of tocilizumab on myocardial salvage in patients with acute ST-elevation myocardial infarction (STEMI).

Open Heart 2019;6(2):e001108. Epub 2019 Oct 15.

Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Introduction: Interleukin-6 (IL-6) may be involved in ischaemia-reperfusion injury and myocardial remodelling after myocardial infarction (MI). We have recently shown that IL-6 inhibition by tocilizumab attenuates systemic inflammation and troponin T-release in patients with acute non-ST elevation MI (NSTEMI). Experimental studies suggest that IL-6 inhibition can limit infarct size through anti-inflammatory mechanisms, but this has not been tested in clinical studies. With the essing the effect of nti--6 treatment in (ASSAIL-MI) trial, we aim to examine whether a single administration of the IL-6 receptor antagonist tocilizumab can increase myocardial salvage in patients with acute ST-elevation MI (STEMI).

Methods And Analysis: The ASSAIL-MI trial is a randomised, double blind, placebo-controlled trial, conducted at three high-volume percutaneous coronary intervention (PCI) centres in Norway. 200 patients with first-time STEMI presenting within 6 hours of the onset of chest pain will be randomised to receive tocilizumab or matching placebo prior to PCI. The patients are followed-up for 6 months. The primary endpoint is the myocardial salvage index measured by cardiac MRI (CMR) 3-7 days after the intervention. Secondary endpoints include final infarct size measured by CMR and plasma markers of myocardial necrosis. Efficacy and safety assessments during follow-up include blood sampling, echocardiography and CMR.

Ethics And Dissemination: Based on previous experience the study is considered feasible and safe. If tocilizumab increases myocardial salvage, further endpoint-driven multicentre trials may be initiated. The ASSAIL-MI trial has the potential to change clinical practice in patients with STEMI.

Registration: Clinicaltrials.gov, identifier NCT03004703.
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http://dx.doi.org/10.1136/openhrt-2019-001108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803013PMC
February 2021

Myocardial fibrosis.

Tidsskr Nor Laegeforen 2018 10 12;138(16). Epub 2018 Oct 12.

Bakgrunn: Myokardfibrose oppstår sekundært til kardial belastning eller skade. I denne oversiktsartikkelen presenteres sentrale aspekter ved myokardfibrose.

Kunnskapsgrunnlag: Vi foretok 2 søk i PubMed som til sammen ga 417 treff. Artiklenes relevans ble vurdert på grunnlag av tittel, sammendrag og eventuell fulltekst. 44 sentrale artikler ble inkludert.

Resultater: Myokardfibrose klassifiseres som interstitiell fibrose og erstatningsfibrose. Fibrose kan forårsake ugunstige endringer i hjertets elektriske og mekaniske funksjon, og forverrer prognosen ved mange hjertesykdommer. Bildediagnostikk og forskning på biomarkører har forbedret mulighetene for å påvise fibrose. Det ultimate målet er å utvikle medikamenter som kan bremse eller reversere myokardfibrose.

Fortolkning: Moderne diagnostikk har forbedret mulighetene for å påvise myokardfibrose og økt forståelsen av fibrosens betydning ved hjertesykdommer. Utvikling av medikamenter som hemmer fibroseutviklingen, vil kunne få stor betydning for moderne hjertemedisin.
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http://dx.doi.org/10.4045/tidsskr.17.1027DOI Listing
October 2018

Interleukin-6 receptor inhibition with tocilizumab induces a selective and substantial increase in plasma IP-10 and MIP-1β in non-ST-elevation myocardial infarction.

Int J Cardiol 2018 Nov 29;271:1-7. Epub 2018 Jun 29.

Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology NTNU, Trondheim, Norway.

Aim: To evaluate the effect of interleukin-6 inhibition with tocilizumab on the cytokine network in patients with acute non-ST-elevation myocardial infarction (NSTEMI).

Methods: 117 patients with acute NSTEMI were randomised to an intravenous infusion of 280 mg tocilizumab or placebo prior to coronary angiography. Blood samples were obtained at baseline, at 6 consecutive points in time during hospitalisation, and at follow-up after 3 and 6 months. Cytokines (n = 27) were analysed with a multiplex cytokine assay.

Results: Using a mixed between-within subjects analysis of variance, we observed a significant (p < 0.001) between-group difference in changes for interferon gamma-inducible protein (IP-10) and macrophage inflammatory protein-1β (MIP-1β), due to significant increases in the tocilizumab group during hospitalisation (i.e., IP-10 median change from baseline during hospitalisation (m), placebo: 3 (-60, 68) pg/ml vs tocilizumab: 209 (69, 335) pg/ml; MIP-1β m, placebo: 5 (-2, 12) pg/ml vs tocilizumab: 39 (24, 63) pg/ml). MIP-1β was inversely correlated to troponin T (r = -0.28, p < 0.05) and neutrophils (r = -0.32, p < 0.05) in the tocilizumab group. In contrast, tocilizumab had only modest or no effects on the other examined cytokines.

Conclusions: Tocilizumab led to a selective and substantial increase in IP-10 and MIP-1β during the acute phase of NSTEMI, with no or only minor effects on the other measured cytokines. ClinicalTrials.gov, NCT01491074.
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http://dx.doi.org/10.1016/j.ijcard.2018.04.136DOI Listing
November 2018

Myocardial Strain Rate by Anatomic Doppler Spectrum: First Clinical Experience Using Retrospective Spectral Tissue Doppler from Ultra-High Frame Rate Imaging.

Ultrasound Med Biol 2017 09 23;43(9):1919-1929. Epub 2017 Jun 23.

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; Department of Cardiology, St. Olav Hospital, Trondheim, Norway.

Strain rate imaging by tissue Doppler (TDI) is vulnerable to stationary reverberations and noise (clutter). Anatomic Doppler spectrum (ADS) presents retrospective spectral Doppler from ultra-high frame rate imaging (UFR-TDI) data for a region of interest, that is, ventricular wall or segment, at one time instance. This enables spectral assessment of strain rate (SR) without the influence of clutter. In this study, we assessed SR with ADS and conventional TDI in 20 patients with a recent myocardial infarction and 10 healthy volunteers. ADS-based SR correlated with fraction of scarred myocardium of the left ventricle (r = 0.68, p < 0.001), whereas SR by conventional TDI did not (r = 0.23, p = 0.30). ADS identified scarred myocardium and ADS Visual was the only method that differentiated transmural from non-transmural distribution of myocardial scar on a segmental level (p = 0.002). Finally, analysis of SR by ADS was feasible in a larger number of segments compared with SR by conventional TDI (p < 0.001).
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http://dx.doi.org/10.1016/j.ultrasmedbio.2017.05.016DOI Listing
September 2017

Effect of interleukin-6 inhibition on coronary microvascular and endothelial function in myocardial infarction.

Heart 2017 10 21;103(19):1521-1527. Epub 2017 Apr 21.

Clinic of Cardiology, St Olavs Hospital, Trondheim, Norway.

Objective: Interleukin-6 (IL-6) is a driver of inflammation and associated endothelial cell activation in acute coronary syndromes. We evaluated the effect of the IL-6 receptor antagonist tocilizumab on coronary microvascular function and endothelial dysfunction measured by coronary flow reserve (CFR) and markers of endothelial cell activation in patients with non-ST-elevation myocardial infarction (NSTEMI).

Methods: This substudy was part of a two-centre, double-blind, randomised, placebo-controlled trial evaluating the effect of a single dose of tocilizumab in NSTEMI. Markers of endothelial cell activation (vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule-1 and von Willebrand factor) were assessed in 117 patients. In 42 of these patients, 20 assigned to placebo and 22 to tocilizumab, we measured CFR. Blood samples were obtained at seven consecutive time points between day 1 and 3. CFR was measured by transthoracic echocardiography during hospitalisation and after 6 months.

Results: Tocilizumab did not affect CFR during hospitalisation (tocilizumab: 3.4±0.8 vs placebo: 3.3±1.2, p=0.80). CFR improved significantly in both groups at 6 months. Patients in the tocilizumab group had significantly higher area under the curve for VCAM-1 (median 622 vs 609 ng/mL/hour, tocilizumab and placebo respectively, p=0.003). There were inverse correlations between VCAM-1 and CFR in the placebo (hospitalisation: r=-0.74, p<0.01, 6 months: r=-0.59, p<0.01), but not in the tocilizumab group (hospitalisation: r=0.20, p=0.37, 6 months r=-0.28, p=0.20).

Conclusions: Tocilizumab did not affect CFR during hospitalisation or after 6 months. Tocilizumab increased VCAM-1 levels during hospitalisation, but this was not associated with reduced CFR in these patients.
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http://dx.doi.org/10.1136/heartjnl-2016-310875DOI Listing
October 2017

Effect of a single dose of the interleukin-6 receptor antagonist tocilizumab on inflammation and troponin T release in patients with non-ST-elevation myocardial infarction: a double-blind, randomized, placebo-controlled phase 2 trial.

Eur Heart J 2016 Aug 8;37(30):2406-13. Epub 2016 May 8.

Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Oslo, Norway K.G. Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway Centre for Heart Failure Research, University of Oslo, Oslo, Norway.

Aims: Interleukin-6 (IL-6) contributes to atherosclerotic plaque destabilization and is involved in myocardial injury during ischaemia-reperfusion. Interleukin-6 is therefore a potential therapeutic target in myocardial infarction (MI). We hypothesized that the IL-6 receptor antagonist tocilizumab would attenuate inflammation, and secondarily reduce troponin T (TnT) release in non-ST-elevation MI (NSTEMI).

Methods And Results: In a two-centre, double-blind, placebo-controlled trial, 117 patients with NSTEMI were randomized at a median of 2 days after symptom onset to receive placebo (n = 59) or tocilizumab (n = 58), administered as a single dose prior to coronary angiography. High sensitivity (hs) C-reactive protein and hsTnT were measured at seven consecutive timepoints between Days 1 and 3. The area under the curve (AUC) for high-sensitivity C-reactive protein was the primary endpoint. The median AUC for high-sensitivity C-reactive protein during hospitalization was 2.1 times higher in the placebo than in the tocilizumab group (4.2 vs. 2.0 mg/L/h, P < 0.001). Also, the median AUC for hsTnT during hospitalization was 1.5 times higher in the placebo group compared with the tocilizumab group (234 vs. 159 ng/L/h, P = 0.007). The differences between the two treatment groups were observed mainly in (i) patients included ≤2 days from symptom onset and (ii) patients treated with percutaneous coronary intervention (PCI). No safety issues in the tocilizumab group were detected during 6 months of follow-up.

Conclusion: Tocilizumab attenuated the inflammatory response and primarily PCI-related TnT release in NSTEMI patients.
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http://dx.doi.org/10.1093/eurheartj/ehw171DOI Listing
August 2016

[An unusual cause of dyspnea].

Tidsskr Nor Laegeforen 2016 04 5;136(6):543. Epub 2016 Apr 5.

Klinikk for hjertemedisin St. Olavs hospital.

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http://dx.doi.org/10.4045/tidsskr.15.0561DOI Listing
April 2016

Aerobic Interval Training Reduces the Burden of Atrial Fibrillation in the Short Term: A Randomized Trial.

Circulation 2016 Feb 5;133(5):466-73. Epub 2016 Jan 5.

From the K.G. Jebsen Center of Exercise in Medicine (V.M., B.M.N., A.-E.T., U.W., J.P.L.), Department of Circulation and Medical Imaging (B.H.A., A.S., O.R.), Norwegian University of Science and Technology, Trondheim, Norway; and Department of Cardiology, St. Olavs Hospital, Trondheim, Norway (V.M., B.H.A., A.S., O.R., J.P.L.).

Background: Exercise training is an effective treatment for important atrial fibrillation (AF) comorbidities. However, a high level of endurance exercise is associated with an increased AF prevalence. We assessed the effects of aerobic interval training (AIT) on time in AF, AF symptoms, cardiovascular health, and quality of life in AF patients.

Methods And Results: Fifty-one patients with nonpermanent AF were randomized to AIT (n=26) consisting of four 4-minute intervals at 85% to 95% of peak heart rate 3 times a week for 12 weeks or to a control group (n=25) continuing their regular exercise habits. An implanted loop recorder measured time in AF continuously from 4 weeks before to 4 weeks after the intervention period. Cardiac function, peak oxygen uptake (o2peak), lipid status, quality of life, and AF symptoms were evaluated before and after the 12-week intervention period. Mean time in AF increased from 10.4% to 14.6% in the control group and was reduced from 8.1% to 4.8% in the exercise group (P=0.001 between groups). AF symptom frequency (P=0.006) and AF symptom severity (P=0.009) were reduced after AIT. AIT improved o2peak, left atrial and ventricular ejection fraction, quality-of-life measures of general health and vitality, and lipid values compared with the control group. There was a trend toward fewer cardioversions and hospital admissions after AIT.

Conclusions: AIT for 12 weeks reduces the time in AF in patients with nonpermanent AF. This is followed by a significant improvement in AF symptoms, o2peak, left atrial and ventricular function, lipid levels, and QoL.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01325675.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.115.018220DOI Listing
February 2016

Cardiac function assessed by exercise echocardiography on the first morning after coronary artery bypass grafting.

Clin Physiol Funct Imaging 2016 Jul 23;36(4):274-80. Epub 2014 Dec 23.

Department of Cardiology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.

Cardiac surgery patients are urged to resume light physical activity on the first postoperative day, even if cardiac function may not have recovered fully after the operation. To elucidate the postoperative recovery process, we examined cardiac surgery patients with exercise echocardiography before and on the first day after the operation. Patients undergoing on-pump coronary artery bypass grafting were examined with echocardiography during semirecumbent cycle exercise. Patients exercised for five minutes at 10 W intensity and five minutes at 30 W intensity in bed with the upper body supported to approximately 30°. Fourteen patients were studied. Mitral annulus excursion and pulsed wave Doppler from the left ventricular outflow tract indicated postoperatively reduced cardiac stroke volume. Early diastolic tissue velocities of the mitral annulus were reduced, and early trans-mitral flow velocity was increased. The ratio between early mitral flow velocity and early diastolic mitral tissue velocity was increased postoperatively, indicating impaired left ventricular relaxation and increased left atrial pressure. Postoperative systolic mitral annulus tissue velocities were similar to preoperative velocities, indicating maintained systolic function. Postoperative exercise was associated with improvements in myocardial function indices and cardiac stroke volume similar to preoperative improvements. There were no signs of further deterioration in myocardial function during 30 W exercise. In summary, reduced left ventricular diastolic function after surgery resulted in reduced cardiac stroke volume, increased left atrial pressure and a higher rate of perceived exertion on the first postoperative day.
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http://dx.doi.org/10.1111/cpf.12224DOI Listing
July 2016

[A man in his 60's with chest pain with chest pain and functional dyspnea].

Tidsskr Nor Laegeforen 2014 Nov 25;134(22):2167-71. Epub 2014 Nov 25.

Klinikk for hjertemedisin St. Olavs hospital og Institutt for sirkulasjon og bildediagnostikk Norges teknisk-naturvitenskapelige universitet.

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http://dx.doi.org/10.4045/tidsskr.14.0538DOI Listing
November 2014

Quantification of aortic regurgitation using high-pulse repetition frequency three-dimensional colour Doppler.

Eur Heart J Cardiovasc Imaging 2014 Jun 15;15(6):615-22. Epub 2013 Dec 15.

Department of Cardiology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway MI lab and Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Aims: The aim of this study was to validate and assess the feasibility of a previously described method using multibeam high-pulse repetition frequency (HPRF) colour Doppler to quantify the vena contracta area (VCA) in aortic regurgitation (AR).

Methods: Twenty-nine patients with mild to severe AR were studied. Regurgitant volume and fraction measured by magnetic resonance imaging (MRI) were used as the standard of reference. The VCA was measured automatically by combining the Doppler power from multiple beams with a priori knowledge of the individual beam profiles, to give an absolute measurement of the VCA. The regurgitant volume was calculated as the product of the VCA and the velocity time integral, measured separately by continuous wave Doppler.

Results: The Spearman's rank correlation between regurgitant volume by MRI and multibeam HPRF colour Doppler was rs = 0.73 (P < 0.01), with 95% limits of agreement of -14.4 ± 29.1 mL. The mean difference between the methods in those with MRI regurgitant volume of ≥30 mL (n = 14) was -7.6 (95% confidence interval -13.9 to -1.2) mL.

Conclusion: There was good agreement between MRI and multibeam HPRF colour Doppler in patients with moderate to severe AR, while agreement for those with mild AR was modest.
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http://dx.doi.org/10.1093/ehjci/jet255DOI Listing
June 2014

Ultra-high frame rate tissue Doppler imaging.

Ultrasound Med Biol 2014 Jan 7;40(1):222-31. Epub 2013 Nov 7.

MI Lab and Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address:

We describe a new tissue Doppler imaging (TDI) method, ultra-high frame rate tissue Doppler imaging (UFR-TDI). With two broad transmit beams covering only the ventricular walls, we achieve 1200 frames/s in a four-chamber apical view. We examined 10 healthy volunteers to study the feasibility of this method. Ultra-high-frame-rate TDI provided peak annular velocities and time to peak S' intervals in good agreement with those measured with conventional TDI. Moreover, UFR-TDI provided additional information in early and late systole: In all subjects, the method was able to separate the timing of electrical activation, start of mechanical contraction, mitral valve closure and start of ejection. The earliest mechanical activation was seen before mitral valve closure. The method was also able to measure the propagation speed of the mechanical wave created by aortic valve closure.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2013.09.012DOI Listing
January 2014

Heart transplant systolic and diastolic function is impaired by prolonged pretransplant graft ischaemic time and high donor age: an echocardiographic study.

Eur J Cardiothorac Surg 2013 Aug 8;44(2):e97-104. Epub 2013 May 8.

Department of Cardiology, Oslo University Hospital HF, Rikshospitalet, Oslo, Norway.

Objectives: Due to the need for suitable donors for heart transplantation (HTx), older grafts and grafts with prolonged graft ischaemic time (GIT) are accepted. The impact of GIT and donor age on post-transplant cardiac function has not been examined with either newer echocardiographic techniques (tissue Doppler imaging, TDI) or cardiopulmonary exercise testing (CPET). Thus, we studied the influence of GIT and donor age on post-transplant cardiac function and exercise capacity.

Methods: Fifty-two stable recipients underwent echocardiography with colour TDI and CPET at a median of 4 years after HTx. Left ventricular (LV) systolic (s') and early diastolic (e') mitral annular velocities, right ventricular (RV) s', RVe' as well as LV ejection fraction (EF) and VO(2peak) were analysed.

Results: HTx recipients with GIT ≥ median value (200 min) had significantly lower septal LVs' (15%, P = 0.005), LVEF (9%, P = 0.015), RVs' (21%, P = 0.007), septal LVe' (22%, P = 0.001) and RVe' velocities (23%, P = 0.011), and slightly lower VO(2peak) (P = 0.098). Recipients with grafts from donor ≥ median age (37 years) had significantly lower LVe' velocities (septal LVe' P = 0.047 and lateral LVe' P = 0.010), but not LV systolic or RV parameters.

Conclusions: Prolonged GIT impairs both systolic and diastolic function at the interventricular septum and RV free wall, while increasing donor age impairs LV diastolic function. The duration of graft ischaemia and donor age should be taken into account when evaluating for cardiac dysfunction in HTx recipients.
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http://dx.doi.org/10.1093/ejcts/ezt233DOI Listing
August 2013

One year of high-intensity interval training improves exercise capacity, but not left ventricular function in stable heart transplant recipients: a randomised controlled trial.

Eur J Prev Cardiol 2014 Feb 26;21(2):181-91. Epub 2012 Nov 26.

Department of Cardiology, Oslo University Hospital HF, Rikshospitalet, Norway.

Background: Heart transplant recipients have lower exercise capacity and impaired cardiac function compared with the normal population. High-intensity interval training (HIIT) improves exercise capacity and cardiac function in patients with heart failure and hypertension, but the effect on cardiac function in stable heart transplant recipients is not known. Thus, we investigated whether HIIT improved cardiac function and exercise capacity in stable heart transplant recipients by use of comprehensive rest- and exercise-echocardiography and cardiopulmonary exercise testing.

Design And Methods: Fifty-two clinically stable heart transplant recipients were randomised either to HIIT (4 × 4 minutes at 85-95% of peak heart rate three times per week for eight weeks) or to control. Three such eight-week periods were distributed throughout one year. Echocardiography (rest and submaximal exercise) and cardiopulmonary exercise testing were performed at baseline and follow-up.

Results: One year of HIIT increased VO 2peak from 27.7 ± 5.5 at baseline to 30.9 ± 5.0 ml/kg/min at follow-up, while the control group remained unchanged (28.5 ± 7.0 vs. 28.0 ± 6.7 ml/kg per min, p < 0.001 for difference between the groups). Systolic and diastolic left ventricular functions at rest and during exercise were generally unchanged by HIIT.

Conclusions: Whereas HIIT is feasible in heart transplant recipients and effectively improves exercise capacity, it does not alter cardiac systolic and diastolic function significantly. Thus, the observed augmentation in exercise capacity is best explained by extra-cardiac adaptive mechanisms.
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http://dx.doi.org/10.1177/2047487312469477DOI Listing
February 2014

Peak systolic velocity indices are more sensitive than end-systolic indices in detecting contraction changes assessed by echocardiography in young healthy humans.

Eur J Echocardiogr 2011 Dec 22;12(12):924-30. Epub 2011 Sep 22.

MI Lab and Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.

Aims: It remains to be proven whether left ventricular (LV) peak systolic velocity indices (peak systolic annulus tissue velocities, ejection velocity, and strain rate) are more closely related to contraction than LV end-systolic echocardiographic indices (ejection fraction, fractional shortening, systolic annulus displacement, global strain, and ejection velocity time integral). The study aimed to compare the ability of different echocardiographic methods in detecting contraction changes of the LV.

Methods And Results: Thirty-three healthy volunteers (20-32 years) were examined by echocardiography at rest, during 10 μg/kg/min dobutamine (n = 20), and after injection of 15 mg metoprolol (n = 20). The effects of dobutamine and metoprolol on peak systolic velocity indices and end-systolic indices were compared. The relative increase from rest to dobutamine stress and the relative decrease after injection of metoprolol were 62 and -15% for peak systolic annulus tissue velocity, 60 and -11% for LV outflow tract (LVOT) peak velocity, 56 and -11% for peak systolic strain rate, 25 and 1% for ejection fraction, 30 and -1% for systolic mitral annulus displacement, 30 and -5% for LVOT velocity time integral, and 21 and -3% for global strain, respectively. The changes of the peak systolic indices were significantly higher (all P < 0.05) than the changes of the end-systolic indices.

Conclusion: Peak systolic velocity indices (mitral annulus tissue velocities, ejection velocities, and strain rate) exhibited greater variation than end-systolic indices during inotropic alterations from which it is assumed that they better reflected LV contraction.
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http://dx.doi.org/10.1093/ejechocard/jer178DOI Listing
December 2011

Aerobic interval training increases peak oxygen uptake more than usual care exercise training in myocardial infarction patients: a randomized controlled study.

Clin Rehabil 2012 Jan 21;26(1):33-44. Epub 2011 Sep 21.

KG Jebsen Center of Exercise in Medicine, Norwegian University of Science and Technology, Department of Circulation and Medical Imaging, Trondheim, Norway.

Objective: Exercise capacity strongly predicts survival and aerobic interval training (AIT) increases peak oxygen uptake effectively in cardiac patients. Usual care in Norway provides exercise training at the hospitals following myocardial infarction (MI), but the effect and actual intensity of these rehabilitation programmes are unknown.

Design: Randomized controlled trial.

Setting: Hospital cardiac rehabilitation.

Subjects: One hundred and seven patients, recruited two to 12 weeks after MI, were randomized to usual care rehabilitation or treadmill AIT.

Interventions: Usual care aerobic group exercise training or treadmill AIT as 4 × 4 minutes intervals at 85-95% of peak heart rate. Twice weekly exercise training for 12 weeks.

Main Measures: The primary outcome measure was peak oxygen uptake. Secondary outcome measures were endothelial function, blood markers of cardiovascular disease, quality of life, resting heart rate, and heart rate recovery.

Results: Eighty-nine patients (74 men, 15 women, 57.4 ± 9.5 years) completed the programme. Peak oxygen uptake increased more (P = 0.002) after AIT (from 31.6 ± 5.8 to 36.2 ± 8.6 mL·kg(-1)·min(-1), P < 0.001) than after usual care rehabilitation (from 32.2 ± 6.7 to 34.7 ± 7.9 mL·kg(-1)·min(-1), P < 0.001). The AIT group exercised with significantly higher intensity in the intervals compared to the highest intensity in the usual care group (87.3 ± 3.9% versus 78.7 ± 7.2% of peak heart rate, respectively, P < 0.001). Both programmes increased endothelial function, serum adiponectin, and quality of life, and reduced serum ferritin and resting heart rate. High-density lipoprotein cholesterol increased only after AIT.

Conclusions: AIT increased peak oxygen uptake more than the usual care rehabilitation provided to MI patients by Norwegian hospitals.
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http://dx.doi.org/10.1177/0269215511405229DOI Listing
January 2012

One-arm maximal strength training improves work economy and endurance capacity but not skeletal muscle blood flow.

J Sports Sci 2011 Jan;29(2):161-70

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.

Maximal strength training with a focus on maximal mobilization of force in the concentric phase improves endurance performance that employs a large muscle mass. However, this has not been studied during work with a small muscle mass, which does not challenge convective oxygen supply. We therefore randomized 23 adult females with no arm-training history to either one-arm maximal strength training or a control group. The training group performed five sets of five repetitions of dynamic arm curls against a near-maximal load, 3 days a week for 8 weeks. This training increased maximal strength by 75% and improved rate of force development during both strength and endurance exercise, suggesting that each arm curl became more efficient. This coincided with a 17-18% reduction in oxygen cost at standardized submaximal workloads (work economy), and a 21% higher peak oxygen uptake and 30% higher peak load during maximal arm endurance exercise. Blood flow assessed by Doppler ultrasound in the axillary artery supplying the working biceps brachii and brachialis muscles could not explain the training-induced adaptations. These data suggest that maximal strength training improved work economy and endurance performance in the skeletal muscle, and that these effects are independent of convective oxygen supply.
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http://dx.doi.org/10.1080/02640414.2010.529454DOI Listing
January 2011

Recovery of function after acute myocardial infarction evaluated by tissue Doppler strain and strain rate.

J Am Soc Echocardiogr 2010 Apr 3;23(4):432-8. Epub 2010 Mar 3.

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.

Background: The aim of this study was to investigate the changes and time course of recovery of regional myocardial function within the first week following successful primary coronary intervention in patients with first-time ST-segment elevation myocardial infarctions using myocardial deformation analysis, which is more quantitative and thus more objective than the wall motion score.

Methods: Thirty-one consecutive patients admitted with ST-segment elevation myocardial infarctions were studied on days 1, 2, 3, and 7 using strain and strain rate tissue Doppler echocardiography.

Results: The mean peak troponin T level was 7.0 microg/L, and 15 patients had anterior and 16 had inferior infarct localization. Peak systolic strain rate and end-systolic strain increased significantly on day 2, both in segments with moderately reduced function (-0.6 to -1.0 s(-1) vs -8% to -15%, P < .001) and in severely reduced function (-0.2 to -1.0 s(-1) vs 1% to -12%, P < .001), but there were no further changes. Mean wall motion score in infarct related segments decreased significantly from day 1 to day 2 (2.7 to 2.4, P = .001) and from day 3 to day 7 (2.3 to 2.2, P = .001).

Conclusions: Recovery of regional function after ST-segment elevation myocardial infarction occurred within 2 days and could be detected by wall motion score, strain rate, and strain. However, strain and strain rate were better discriminative parameters for the changes in function as well as being better to assess near normalization on day 2. This could have a clinical impact on early management in patients who undergo percutaneous coronary intervention.
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http://dx.doi.org/10.1016/j.echo.2010.01.018DOI Listing
April 2010

High-intensity exercise training in mice with cardiomyocyte-specific disruption of Serca2.

J Appl Physiol (1985) 2010 May 18;108(5):1311-20. Epub 2010 Feb 18.

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, and Department of Medical Imaging, St. Olavs Hospital, Olav Kyrres gate 9, NO-7489 Trondheim, Norway.

Several lines of evidence indicate that the sarco(endo)plasmic reticulum ATPase type 2 (SERCA2) is essential for maintaining myocardial calcium handling and cardiac pump function. Hence, a reduction in SERCA2 abundance is expected to reduce work performance and maximal oxygen uptake (VO2max) and to limit the response to exercise training. To test this hypothesis, we compared VO2max and exercise capacity in mice with cardiac disruption of Serca2 (SERCA2 KO) with control mice (SERCA2 FF). We also determined whether the effects on VO2max and exercise capacity could be modified by high-intensity aerobic exercise training. Treadmill running at 85-90% of VO2max started 2 wk after Serca2 gene disruption and continued for 4 wk. VO2max and maximal running speed were measured weekly in a metabolic chamber. Cardiac function was assessed by echocardiography during light anesthesia. In sedentary SERCA2 KO mice, the aerobic capacity was reduced by 50% and running speed by 28%, whereas trained SERCA2 KO mice were able to maintain maximal running speed despite a 36% decrease in VO2max. In SERCA2 FF mice, both VO2max and maximal running speed increased by training, while no changes occurred in the sedentary group. Left ventricle dimensions remained unchanged by training in both genotypes. In contrast, training induced right ventricle hypertrophy in SERCA2 KO mice. In conclusion, the SERCA2 protein is essential for sustaining cardiac pump function and exercise capacity. Nevertheless, SERCA2 KO mice were able to maintain maximal running speed in response to exercise training despite a large decrease in VO2max.
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http://dx.doi.org/10.1152/japplphysiol.01133.2009DOI Listing
May 2010

Aerobic interval training versus continuous moderate exercise after coronary artery bypass surgery: a randomized study of cardiovascular effects and quality of life.

Am Heart J 2009 Dec;158(6):1031-7

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Background: Peak oxygen uptake (Vo(2peak)) strongly predicts mortality in cardiac patients. We compared the effects of aerobic interval training (AIT) versus moderate continuous training (MCT) on Vo(2peak) and quality of life after coronary artery bypass grafting (CABG).

Methods: Fifty-nine CABG patients were randomized to either AIT at 90% of maximum heart rate or MCT at 70% of maximum heart rate, 5 d/wk, for 4 weeks at a rehabilitation center. Primary outcome was Vo(2peak), at baseline, after rehabilitation (4 weeks), and after 6 months of home-based exercise (6 months).

Results: Vo(2peak) increased between baseline and 4 weeks in AIT (27.1 +/- 4.5 vs 30.4 +/- 5.5 mL.kg(-1).min(-1), P < .001) and MCT (26.2 +/- 5.2 vs 28.5 +/- 5.6 mL.kg(-1).min(-1), P < .001; group difference, not significant). Aerobic interval training increased Vo(2peak) between 4 weeks and 6 months (30.4 +/- 5.5 vs 32.2 +/- 7.0 mL.kg(-1).min(-1), P < .001), with no significant change in MCT (28.5 +/- 5.6 vs 29.5 +/- 5.7 mL.kg(-1).min(-1)). Quality of life improved in both groups from baseline to 4 weeks, remaining improved at 6 months. There were no changes in echocardiographic systolic and diastolic left ventricular function. Adiponectin increased between 4 weeks and 6 months in both groups (group differences, not significant).

Conclusions: Four weeks of intense training increased Vo(2peak) significantly after both AIT and MCT. Six months later, the AIT group had a significantly higher Vo(2peak) than MCT. The results indicate that AIT and MCT increase Vo(2peak) similarly in the short term, but with better long-term effect of AIT after CABG.
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http://dx.doi.org/10.1016/j.ahj.2009.10.003DOI Listing
December 2009

Onset of exercise training 14 days after uncomplicated myocardial infarction: a randomized controlled trial.

Eur J Cardiovasc Prev Rehabil 2010 Aug;17(4):387-92

Clinical Services, St. Olav University Hospital, 7006 Trondheim, Norway.

Background: Exercise training is an important part of cardiac rehabilitation to reduce morbidity and mortality. Low-intensity exercise training can start as soon as the myocardial infarction (MI) patient is stable. Our objective was to evaluate the effect of an early start of exercise training in MI patients.

Design: A randomized controlled trial.

Methods: Thirty-nine MI patients were randomized to either an early start of exercise training group (EG) or to a delayed start control group (CG). The EG participated in an outpatient low-intensity EG (phase 2a) two times a week for 4 weeks before entering ordinary exercise training of moderate-to-high intensity (phase 2b). CG entered phase 2b directly after 4 weeks of delay. Primary outcome measure was peak oxygen consumption (VO2peak), measured at baseline, after 4 weeks and after 16 weeks. Secondary outcome measure was health-related quality of life.

Results: VO2peak did not change from baseline to 4 weeks, either in EG [30.6+/-6.7 ml/kg/min vs. 30.7+/-6.2 ml/kg/min, not significant (NS)] or CG (29.8+/-6.1 ml/kg/min vs. 30.7+/-6.2 ml/kg/min, NS). After 16 weeks VO2peak increased in both groups to 33.1+/-7.1 ml/kg/min in EG (P<0.005) and 33.0 ml/kg/min+/-8.6 in CG (P<0.005), group differences NSH. Health-related quality of life increased in every domain but physical functioning for both groups (group differences NS).

Conclusion: An early start of exercise training did not increase VO2peak compared to 4 weeks of delay. For low-risk patients with high motivation for exercise training, home-based walking is an option as a moderate start of cardiac rehabilitation the first weeks after MI.
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http://dx.doi.org/10.1097/HJR.0b013e328333edf9DOI Listing
August 2010

Quantification of mitral regurgitation using high pulse repetition frequency three-dimensional color Doppler.

J Am Soc Echocardiogr 2010 Jan 13;23(1):1-8. Epub 2009 Nov 13.

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.

Background: The aim of this study was to validate a novel method of determining vena contracta area (VCA) and quantifying mitral regurgitation using multibeam high-pulse repetition frequency (HPRF) color Doppler.

Methods: The Doppler signal was isolated from the regurgitant jet, and VCA was found by summing the Doppler power from multiple beams within the vena contracta region, where calibration was done with a reference beam. In 27 patients, regurgitant volume was calculated as the product of VCA and the velocity-time integral of the regurgitant jet, measured by continuous-wave Doppler, and compared with regurgitant volume measured by magnetic resonance imaging (MRI).

Results: Spearman's rank correlation and the 95% limits of agreement between regurgitant volume measured by MRI and by multibeam HPRF color Doppler were r(s) = 0.82 and -3.0 +/- 26.2 mL, respectively.

Conclusion: For moderate to severe mitral regurgitation, there was good agreement between MRI and multibeam HPRF color Doppler. Agreement was lower in mild regurgitation.
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http://dx.doi.org/10.1016/j.echo.2009.10.005DOI Listing
January 2010

Left ventricular myocardial function during the acute phase of a subarachnoid haemorrhage.

Scand Cardiovasc J 2009 Apr;43(2):110-6

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.

Objectives: Previous reports suggest that left myocardial ventricular function changes during the course of a subarachnoid haemorrhage. The aim of this study was to evaluate left myocardial ventricular function with tissue Doppler echocardiography at two time points during the acute phase of a subarachnoid haemorrhage.

Design: Eighteen consecutive patients (median 52 years, range 33-74) with spontaneous subarachnoid haemorrhage and no history of heart disease were examined at 1-5 days and at 6-11 days following ictus. Eighteen control subjects were included for comparison (52 years, 32-72).

Results: Tissue Doppler indices of left ventricular contractility were higher in patients than in controls at both examinations (p<0.001). Indices of left ventricular stroke volume were elevated compared to controls at examination 1 (p<0.05), but not at examination 2. Early diastolic relaxation rate decreased from examination 1 to 2 (p=0.001). Three patients had increased troponin T (range 0.010-0.131 microg/l).

Conclusion: In patients with subarachnoid haemorrhage, systolic and diastolic function is increased compared to healthy controls, suggesting a hyperdynamic and hypervolemic circulation.
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http://dx.doi.org/10.1080/14017430802398116DOI Listing
April 2009

Upright bicycle exercise echocardiography in patients with myocardial infarction shows lack of diastolic, but not systolic, reserve: a tissue Doppler study.

Eur J Echocardiogr 2009 Jun 6;10(4):503-8. Epub 2008 Dec 6.

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim N-7489, Norway.

Aims: The aim of this feasibility study was to compare systolic and diastolic left ventricular (LV) function during upright bicycle exercise in patients with chronic myocardial infarction (MI).

Methods And Results: Eighteen patients with first-time MI and no signs of heart failure at rest underwent upright bicycle exercise at 25, 50, and 75 W, and were compared with 18 age-matched controls. Systolic (S') and early (E') mitral annular velocities and early mitral filling velocity (E) were measured at each stage. LV ejection fraction was lower in the MI group (46 vs. 54%, P < 0.01), while end-diastolic volumes were similar. S' was lower in the MI patients, but increased during exercise in both groups. E' was similar at rest, but increased in the control group only. Early mitral filling (E) increased in both groups, thus the E/E' ratio increased during exercise in the MI group only. Heart rate was similar in both groups.

Conclusions: Upright exercise echocardiography is feasible and can unmask early diastolic dysfunction and increased LV filling pressures in patients with small prior MIs.
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http://dx.doi.org/10.1093/ejechocard/jen312DOI Listing
June 2009

3-D speckle tracking for assessment of regional left ventricular function.

Ultrasound Med Biol 2009 Mar 4;35(3):458-71. Epub 2008 Dec 4.

Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.

Speckle tracking in 2-D ultrasound images has become an established tool for assessment of left ventricular function. The recent development of ultrasound systems with capability to acquire real-time full volume data of the left ventricle makes it possible to perform speckle tracking in three dimensions, and thereby track the real motion of the myocardium. This paper presents a method for assessing local strain and rotation from 3-D speckle tracking in apical full-volume datasets. The method has been tested on simulated ultrasound data based on a computer model of the left ventricle, and on patients with myocardial infarction. When applied on simulated ultrasound data, the method showed good agreement with strain and rotation traces calculated from the reference motion, and the method was able to capture segmental differences in the deformation pattern, although the magnitudes of strains were systematically lower than the reference strains. When applied on patients, the method demonstrated reduced strain in the infarcted areas. Bulls-eye plots of regional strains showed good correspondence with wall motion scoring based on 2-D apical images, although the dyskinetic and hypokinetic regions were not apparent in all strain components.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2008.09.011DOI Listing
March 2009

Regional myocardial long-axis strain and strain rate measured by different tissue Doppler and speckle tracking echocardiography methods: a comparison with tagged magnetic resonance imaging.

Eur J Echocardiogr 2009 Mar 23;10(2):229-37. Epub 2008 Jul 23.

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, MTFS, N-7489 Trondheim, Norway.

Aims: Compare four different echocardiographic methods, based on tissue Doppler imaging (TDI) and speckle tracking (ST) separately or combined, for long-axis strain and strain rate (SR) measurements, using magnetic resonance imaging (MRI) tagging as a reference.

Methods And Results: In 21 subjects (10 with myocardial infarction) peak systolic strain and systolic and early diastolic SR were measured by four different echo methods: (i) two-dimensional (2D) strain (B-mode); (ii) ST (custom software) of segment end-points (B-mode); (iii) similar to (ii), but combining ST with tissue Doppler tracking; (iv) strain from tissue Doppler velocity gradients (VG). Agreement with MRI tagging was better for strain than for SR. Ninety-five per cent limits of agreement were wider for the TDI-VG method, and 2D strain showed negative bias compared with MRI tagging and the other echo methods. Reproducibility was better for 2D strain than for MRI tagging and the other echo methods.

Conclusion: ST alone or combined with TDI seems to be suitable for automated measurements of regional myocardial deformation. The study gives important information on the strengths and weaknesses of the different methods, which is important for further development to increase accuracy and applicability.
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http://dx.doi.org/10.1093/ejechocard/jen201DOI Listing
March 2009

A new tissue Doppler method for examination of left ventricular rotation.

Ultrasound Med Biol 2008 Nov 10;34(11):1741-51. Epub 2008 Jun 10.

Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

This paper introduces a new semiautomatic method for assessing regional left ventricular (LV) rotation that uses the velocity field provided by tissue Doppler imaging (TDI). Left ventricular end-systolic angle of twist estimated by the new method has been compared with rotation by magnetic resonance imaging (MRI) tagging, by 2-D speckle tracking echocardiography (STE) and by a TDI method using the velocity difference between the tangential points on the LV circumference in 21 human subjects. The new TDI method gave lower absolute values for end-systolic twist angle than MRI and STE (agreement -4.1 +/- 2.1 degrees and -2.5 +/- 4.0 degrees, respectively). The reproducibility of the new method was as good as for MRI and STE, but worse than the use of TDI velocities in tangential points. The present study has shown that TDI methods constitute useful alternatives to speckle tracking and MRI, and should be considered in future studies of LV twist and rotation.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2008.03.022DOI Listing
November 2008

High-intensity aerobic exercise improves diastolic function in coronary artery disease.

Scand Cardiovasc J 2008 Apr;42(2):110-7

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.

Objective: To study the effect of aerobic treadmill exercise training with different intensity on left ventricular (LV) function in patients with stable coronary artery disease, using Strain Rate- and Tissue Doppler Imaging.

Design: Seventeen patients were randomly assigned to either moderate (50-60% of peak oxygen uptake (VO(2peak)) or high intensity exercise (80-90% of VO(2peak)) for 10 weeks.

Results: The increase of VO(2peak) was significantly higher (p=0.01) in the high intensity group (17 vs. 8%). Mean LV early diastolic strain rate increased in the high, but not in the moderate, intensity group. For systolic strain rate or mitral annular velocities there were no change after training in either group.

Conclusions: Aerobic treadmill exercise improves early diastolic relaxation in patients with stable coronary artery disease, measured by the mean LV early diastolic strain rate.
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http://dx.doi.org/10.1080/14017430701744477DOI Listing
April 2008

Manganese dipyridoxyl-diphosphate (MnDPDP) as a viability marker in patients with myocardial infarction.

J Magn Reson Imaging 2007 Sep;26(3):720-7

Department of Circulation and Medical Imaging (ISB), Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Purpose: To evaluate contrast accumulation in left ventricular (LV) myocardium after manganese dipyridoxyl-diphosphate (MnDPDP) administration in patients with recent first time myocardial infarction.

Materials And Methods: MnDPDP (5 micromol/kg) was administered to 10 patients with recent myocardial infarction (three to 12 weeks). One slice of interest (SOI) likely to traverse the infarction was chosen, and sectorial pre- and postcontrast longitudinal relaxivity rates (R(1)) and signal changes during infusion were estimated with a fast gradient echo sequence. LV volume and wall thickening were measured in short-axis cine recordings. Infarct localization from R(1) and wall thickening data were compared by vector analyses.

Results: Reduced wall thickening was associated with reduced precontrast R(1) and reduced contrast enhancement. Both remote and infarcted regions showed rapid initial contrast accumulation. In remote regions, this was followed by a continuing slow increase. Mean precontrast R(1) was 0.87 +/- 0.06 second(-1) in infarcted regions and 0.96 +/- 0.03 second(-1) in remote regions (P < 0.001). Mean R(1) change over one hour was 0.24 +/- 0.07 second(-1) in infarcted regions and 0.38 +/- 0.03 second(-1) in remote regions (P < 0.0001).

Conclusion: Remote regions showed larger increases in R(1) than infarcted regions. This is most likely due to selective and slow Mn accumulation in viable myocytes.
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http://dx.doi.org/10.1002/jmri.21065DOI Listing
September 2007

[A 50-year old woman with cor triatriatum].

Tidsskr Nor Laegeforen 2007 Apr;127(8):1056-7

Klinikk for hjertemedisin, St. Olavs Hospital, 7006 Trondheim.

Background: Cor triatriatum is a rare congenital malformation in the heart. A recently published report has indicated that real time transthoracic 3-dimensional echocardiography (3DE) may replace transoesophageal echocardiography (TEE) in the diagnosis of this entity.

Material And Methods: A patient with cor triatriatum was examined with 3DE. The results were compared to established echocardiographic methods, inclusive TEE, and to magnetic resonance imaging (MR).

Results And Interpretation: Due to excellent resolution, TEE is still unrivalled in the assessment of some congenital heart diseases such as cor triatriatum. Real time 3DE may have the potential to replace TEE in the future, but refinement of the method is necessary.
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April 2007
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