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.

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.

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.

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.

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.

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

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.

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

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.

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

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.

Ultra-high frame rate tissue Doppler imaging.

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.

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

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.

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.

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

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.

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

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.