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

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.

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.

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.

Mechanical Wave Velocities in Left Ventricular Walls in Healthy Subjects and Patients With Aortic Stenosis.

BACKGROUND: Mechanical wave velocity (MWV) measurement is a promising method for evaluating myocardial stiffness, because these velocities are higher in patients with myocardial disease. OBJECTIVES: Using high frame rate echocardiography and a novel method for detection of myocardial mechanical waves, this study aimed to estimate the MWVs for different left ventricular walls and events in healthy subjects and patients with aortic stenosis (AS). Feasibility and reproducibility were evaluated. METHODS: This study included 63 healthy subjects and 13 patients with severe AS. All participants underwent echocardiographic examination including 2-dimensional high frame rate recordings using a clinical scanner. Cardiac magnetic resonance was performed in 42 subjects. The authors estimated the MWVs at atrial kick and aortic valve closure in different left ventricular walls using the clutter filter wave imaging method. RESULTS: Mechanical wave imaging in healthy subjects demonstrated the highest feasibility for the atrial kick wave reaching >93% for all 4 examined left ventricular walls. The MWVs were higher for the inferolateral and anterolateral walls (2.2 and 2.6 m/s) compared with inferoseptal and anteroseptal walls (1.3 and 1.6 m/s) (P < 0.05) among healthy subjects. The septal MWVs at aortic valve closure were significantly higher for patients with severe AS than for healthy subjects. CONCLUSIONS: MWV estimation during atrial kick is feasible and demonstrates higher velocities in the lateral walls, compared with septal walls. The authors propose indicators for quality assessment of the mechanical wave slope as an aid for achieving consistent measurements. The discrimination between healthy subjects and patients with AS was best for the aortic valve closure mechanical waves. (Ultrasonic Markers for Myocardial Fibrosis and Prognosis in Aortic Stenosis; NCT03422770).

Cytokine pattern in patients with ST-elevation myocardial infarction treated with the interleukin-6 receptor antagonist tocilizumab.

BACKGROUND: Tocilizumab improves myocardial salvage index (MSI) in patients with ST-elevation myocardial infarction (STEMI), but its mechanisms of action are unclear. Here, we explored how cytokines were affected by tocilizumab and their correlations with neutrophils, C-reactive protein (CRP), troponin T, MSI and infarct size. METHODS: STEMI patients were randomised to receive a single dose of 280 mg tocilizumab (n=101) or placebo (n=98) before percutaneous coronary intervention. Blood samples were collected before infusion of tocilizumab or placebo at baseline, during follow-up at 24-36, 72-168 hours, 3 and 6 months. 27 cytokines were analysed using a multiplex cytokine assay. Cardiac MRI was performed during hospitalisation and 6 months. RESULTS: Repeated measures analysis of variance showed significant (p<0.001) between-group difference in changes for IL-6, IL-8 and IL-1ra due to an increase in the tocilizumab group during hospitalisation. IL-6 and IL-8 correlated to neutrophils in the placebo group (r=0.73, 0.68, respectively), which was attenuated in the tocilizumab group (r=0.28, 0.27, respectively). A similar pattern was seen for MSI and IL-6 and IL-8 in the placebo group (r=-0.29, -0.25, respectively) in patients presenting ≤3 hours from symptom onset, which was attenuated in the tocilizumab group (r=-0.09,-0.14, respectively). CONCLUSIONS: Tocilizumab increases IL-6, IL-8 and IL-1ra in STEMI. IL-6 and IL-8 show correlations to neutrophils/CRP and markers of cardiac injury in the placebo group that was attenuated in the tocilizumab group. This may suggest a beneficial effect of tocilizumab on the ischaemia-reperfusion injury in STEMI patients. TRIAL REGISTRATION NUMBER: NCT03004703.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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.

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.

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

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.

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).

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 ASSessing the effect of Anti-IL-6 treatment in MI (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.

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

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-1ß (MIP-1ß), due to significant increases in the tocilizumab group during hospitalisation (i.e., IP-10 median change from baseline during hospitalisation (mΔ), placebo: 3 (-60, 68) pg/ml vs tocilizumab: 209 (69, 335) pg/ml; MIP-1ß mΔ, placebo: 5 (-2, 12) pg/ml vs tocilizumab: 39 (24, 63) pg/ml). MIP-1ß 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-1ß during the acute phase of NSTEMI, with no or only minor effects on the other measured cytokines. ClinicalTrials.gov, NCT01491074.

[A 50-year old woman with cor triatriatum]. / 50 år gammel kvinne med rask hjerteaksjon.

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.

[Exercise training in cardiovascular diseases]. / Fysisk trening ved hjerte- og karsykdommer.

BACKGROUND: Physical activity and exercise training are effective in prevention, treatment and rehabilitation of cardiovascular disease, but the dose-response relationship is insufficiently documented. METHOD: The manuscript is based on existing guidelines and searches in Pubmed for the period 1990-2006. RESULTS AND INTERPRETATION: Exercise training improves maximum oxygen consumption and prognosis in patients with cardiovascular disease. A single weekly bout of exercise reduces mortality from stroke and ischemic heart disease, but larger doses may provide additional protection. In patients with coronary heart disease, high intensity exercise seems to be more effective in improving maximal oxygen consumption than moderate exercise, but it is not known if such exercise is also more effective in improving survival. Further studies are also required to establish the safety of such exercise. Exercise has few contraindications, but patients should be screened in advance with an exercise-ECG. Future studies should to a larger extent include female, elderly and high-risk patients, and be precise in prescribing and reporting exercise intensity, duration and frequency. Maximum oxygen consumption is an accurate measure of cardiovascular fitness and a strong and independent prognostic marker for survival, both in patients and healthy subjects.

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

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).

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

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.