Exercise training and high-sensitivity cardiac troponin-I in patients with heart failure with reduced ejection fraction.

AIMS: The aims of this sub-study of the SMARTEX trial were (1) to evaluate the effects of a 12-week exercise training programme on serum levels of high sensitivity cardiac troponin I (hs-cTnI) in patients with moderate chronic heart failure (CHF), in New York Heart Association class II-III with reduced ejection fraction (HFrEF) and (2) to explore the associations with left ventricular remodelling, functional capacity and filling pressures measured with N-terminal pro brain natriuretic peptide (NT-proBNP). METHODS AND RESULTS: In this sub-study, 196 patients were randomly assigned to high intensity interval training (HIIT, n = 70), moderate continuous training (MCT, n = 59) or recommendation of regular exercise (RRE), (n = 67) for 12 weeks. To reveal potential difference between structured intervention and control, HIIT and MCT groups were merged and named supervised exercise training (SET) group. The RRE group constituted the control group (CG). To avoid contributing factors to myocardial injury, we also evaluated changes in patients without additional co-morbidities (atrial fibrillation, hypertension, diabetes mellitus, and chronic obstructive pulmonary disease). The relationship between hs-cTnI and left ventricular end-diastolic diameter (LVEDD), VO2peak, and NT-proBNP was analysed by linear mixed models. At 12 weeks, Hs-cTnI levels were modestly but significantly reduced in the SET group from median 11.9 ng/L (interquartile ratio, IQR 7.1-21.8) to 11.5 ng/L (IQR 7.0-20.7), P = 0.030. There was no between-group difference (SET vs. CG, P = 0.116). There was a numerical but not significant reduction in hs-cTnI for the whole population (P = 0.067) after 12 weeks. For the sub-group of patients without additional co-morbidities, there was a significant between-group difference: SET group (delta -1.2 ng/L, IQR -2.7 to 0.1) versus CG (delta -0.1 ng/L, IQR -0.4 to 0.7), P = 0.007. In the SET group, hs-cTnI changed from 10.9 ng/L (IQR 6.0-22.7) to 9.2 ng/L (IQR 5.2-20.5) (P = 0.002), whereas there was no change in the CG (6.4 to 5.8 ng/L, P = 0.64). Changes in hs-cTnI (all patients) were significantly associated with changes in; LVEDD, VO2peak, and NT-proBNP, respectively. CONCLUSIONS: In patients with stable HFrEF, 12 weeks of structured exercise intervention was associated with a modest, but significant reduction of hs-cTnI. There was no significant difference between intervention group and control group. In the sub-group of patients without additional co-morbidities, this difference was highly significant. The alterations in hs-cTnI were associated with reduction of LVEDD and natriuretic peptide concentrations as well as improved functional capacity.

Segmental myocardial viability by echocardiography at rest.

BACKGROUND: Myocardial viability assessment adds value to the therapeutic decision-making of patients with ischemic heart disease. In this feasibility study, we investigated whether established echocardiographic measurements of post-systolic shortening (PSS), strain, strain rate and wall motion score (WMS) can discover viable myocardial segments. Our hypothesis is that non-viable myocardial segments are both akinetic and without PSS. METHODS: The study population consisted of 26 examinations strictly selected by visible dysfunction. We assessed WMS, strain by speckle tracking and strain rate by tissue Doppler. The segments (16*26 = 416) were categorized into either normokinetic/hypokinetic or akinetic/dyskinetic and whether there was PSS. The reference method was the presence of scar with segmental percentage volume scar fraction >50%, detected by late gadolinium-enhanced cardiovascular magnetic resonance. Agreement with echocardiography was evaluated by Kappa coefficient. RESULTS: WMS had Kappa coefficient 0.43 (sensitivity 99%, specificity 35%). Kappa coefficient of strain was 0.28 (sensitivity 98%, specificity 23%). By combining PSS in akinetic segments with WMS and strain, the Kappa coefficient was 0.06 and 0.08 respectively. CONCLUSION: Segmental viability was best shown by the presence of systolic function. Post-systolic shortening adds no value to the assessment of segmental myocardial viability.

Regional motion of the AV-plane is related to the cardiac anatomy and deformation of the AV-plane. Data from the HUNT study.

The study examines global and regional systolic shortening of the left (LV) and right ventricle (RV) in 1266 individuals without evidence of heart disease in the third wave of the HUNT study. Regional mitral annular systolic displacement (mitral annular plane systolic excursion [MAPSE]) was 1.5 cm in the septum and anterior walls, 1.6 cm in the lateral wall and 1.7 cm in the inferior wall, global mean 1.6 cm. Peak systolic velocity S' was 8.0, 8.3, 8.8 and 8.6 cm/s in the same walls (global mean 8.7 cm/s). All measures of LV longitudinal shortening correlated, mean MAPSE and S' also correlated with stroke volume (SV) and ejection fraction (EF). Global longitudinal strain by either method correlated with MAPSE, S' and EF, but not with SV, reflecting a systematic difference. S' and MAPSE correlated with early annular diastolic velocity (e'), reflecting that e' is the recoil from systole. Mean displacement was 2.8 (0.5) cm in the tricuspid annulus (tricuspid annular plane systolic excursion [TAPSE]). Normal values by age and sex are provided. Both TAPSE and S' were lower in women, where body size explained the sex difference. Normalisation of MAPSE and S' for wall length reduced intra-individual variation of displacement and velocity by 80%-90%, showing regional MAPSE to be related to LV wall length, and that longitudinal wall strain was relatively uniform. Displacement and S' were lowest in the septum and highest in the left and right free walls, shows systolic bending of the AV-plane into a U-shape, relating to the total cardiac volume changes during the heart cycle.

Retrospective Ultrasound Doppler Quantification Using a Single Acquisition in Healthy Adults.

OBJECTIVE: Using an experimental tool for retrospective ultrasound Doppler quantification-with high temporal resolution and large spatial coverage-simultaneous flow and tissue measurements were obtained. We compared and validated these experimental values against conventional measurements to determine if the experimental acquisition produced trustworthy tissue and flow velocities. METHODS: We included 21 healthy volunteers. The only exclusion criterion was the presence of an irregular heartbeat. Two ultrasound examinations were performed for each participant, one using conventional and one using experimental acquisition. The experimental acquisition used multiple plane wave emissions combined with electrocardiography stitching to obtain continuous data with over 3500 frames per second. With two recordings covering a biplane apical view of the left ventricle, we retrospectively extracted selected flow and tissue velocities. RESULTS: Flow and tissue velocities were compared between the two acquisitions. Statistical testing showed a small but significant difference. We also exemplified the possibility of extracting spectral tissue Doppler from different sample volumes in the myocardium within the imaging sector, showing a decrease in the velocities from the base to the apex. CONCLUSION: This study demonstrates the feasibility of simultaneous, retrospective spectral and color Doppler of both tissue and flow from an experimental acquisition covering a full sector width. The measurements were significantly different between the two acquisitions but were still comparable, as the biases were small compared to clinical practice, and the two acquisitions were not done simultaneously. The experimental acquisition also enabled the study of deformation by simultaneous spectral velocity traces from all regions of the image sector.

Automated tissue Doppler imaging for identification of occluded coronary artery in patients with suspected non-ST-elevation myocardial infarction.

PURPOSE: Identification of regional dysfunction is important for early risk stratification in patients with suspected non-ST-elevation myocardial infarction (NSTEMI). Strain echocardiography enables quantification of segmental myocardial deformation. However, the clinical use is hampered by time-consuming manual measurements. We aimed to evaluate whether an in-house developed software for automated analysis of segmental myocardial deformation based on tissue Doppler imaging (TDI) could predict coronary occlusion in patients with suspected NSTEMI. METHODS: Eighty-four patients with suspected NSTEMI were included in the analysis. Echocardiography was performed at admission. Strain, strain rate and post-systolic shortening index (PSI) were analyzed by the automated TDI-based tool and the ability to predict coronary occlusion was assessed. For comparison, strain measurements were performed both by manual TDI-based analyses and by semi-automatic speckle tracking echocardiography (STE). All patients underwent coronary angiography. RESULTS: Seventeen patients had an acute coronary occlusion. Global strain and PSI by STE were able to differentiate occluded from non-occluded culprit lesions (respectively - 15.0% vs. -17.1%, and 8.1% vs. 5.1%, both p-values < 0.05) and identify patients with an acute coronary occlusion (AUC 0.66 for both strain and PSI). Measurements of strain, strain rate and PSI based on TDI were not significantly different between occluded and non-occluded territories. CONCLUSION: Automated measurements of myocardial deformation based on TDI were not able to identify acute coronary occlusion in patients with suspected NSTEMI. However, this study confirms the potential of strain by STE for early risk stratification in patients with chest pain.

Effect of 5 years of exercise training on the cardiovascular risk profile of older adults: the Generation 100 randomized trial.

AIMS: The aim of this study was to compare the effects of 5 years of supervised exercise training (ExComb), and the differential effects of subgroups of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), with control on the cardiovascular risk profile in older adults. METHODS AND RESULTS: Older adults aged 70-77 years from Trondheim, Norway (n = 1567, 50% women), able to safely perform exercise training were randomized to 5 years of two weekly sessions of HIIT [∼90% of peak heart rate (HR), n = 400] or MICT (∼70% of peak HR, n = 387), together forming ExComb (n = 787), or control (instructed to follow physical activity recommendations, n = 780). The main outcome was a continuous cardiovascular risk score (CCR), individual cardiovascular risk factors, and peak oxygen uptake (VO2peak). CCR was not significantly lower [-0.19, 99% confidence interval (CI) -0.46 to 0.07] and VO2peak was not significantly higher (0.39 mL/kg/min, 99% CI -0.22 to 1.00) for ExComb vs. control. HIIT showed higher VO2peak (0.76 mL/kg/min, 99% CI 0.02-1.51), but not lower CCR (-0.32, 99% CI -0.64 to 0.01) vs. control. MICT did not show significant differences compared to control or HIIT. Individual risk factors mostly did not show significant between-group differences, with some exceptions for HIIT being better than control. There was no significant effect modification by sex. The number of cardiovascular events was similar across groups. The healthy and fit study sample, and contamination and cross-over between intervention groups, challenged the possibility of detecting between-group differences. CONCLUSIONS: Five years of supervised exercise training in older adults had little effect on cardiovascular risk profile and did not reduce cardiovascular events. REGISTRATION: ClinicalTrials.gov: NCT01666340.

Moderate continuous or high intensity interval exercise in heart failure with reduced ejection fraction: Differences between ischemic and non-ischemic etiology.

Background: Exercise for heart failure (HF) with reduced ejection fraction (HFrEF) is recommended by guidelines, but exercise mode and intensities are not differentiated between HF etiologies. We, therefore, investigated the effect of moderate or high intensity exercise on left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF) and maximal exercise capacity (peak VO2) in patients with ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM). Methods: The Study of Myocardial Recovery after Exercise Training in Heart Failure (SMARTEX-HF) consecutively enrolled 231 patients with HFrEF (LVEF ≤ 35 %, NYHA II-III) in a 12-weeks supervised exercise program. Patients were stratified for HFrEF etiology (ICM versus NICM) and randomly assigned (1:1:1) to supervised exercise thrice weekly: a) moderate continuous training (MCT) at 60-70 % of peak heart rate (HR), b) high intensity interval training (HIIIT) at 90-95 % peak HR, or c) recommendation of regular exercise (RRE) according to guidelines. LVEDD, LVEF and peak VO2 were assessed at baseline, after 12 and 52 weeks. Results: 215 patients completed the intervention. ICM (59 %; n = 126) compared to NICM patients (41 %; n = 89) had significantly lower peak VO2 values at baseline and after 12 weeks (difference in peak VO2 2.2 mL/(kg*min); p < 0.0005) without differences between time points (p = 0.11) or training groups (p = 0.15). Etiology did not influence changes of LVEDD or LVEF (p = 0.30; p = 0.12), even when adjusting for sex, age and smoking status (p = 0.54; p = 0.12). Similar findings were observed after 52 weeks. Conclusions: Etiology of HFrEF did not influence the effects of moderate or high intensity exercise on cardiac dimensions, systolic function or exercise capacity. Clinical Trial Registration­URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046.

Intraventricular Vector Flow Imaging with Blood Speckle Tracking in Adults: Feasibility, Normal Physiology and Mechanisms in Healthy Volunteers.

This study examines the feasibility of blood speckle tracking for vector flow imaging in healthy adults and describes the physiologic flow pattern and vortex formation in relation to the wall motion in the left ventricle. The study included 21 healthy volunteers and quantified and visualized flow patterns with high temporal resolution down to a depth of 10-12 cm without the use of contrast agents. Intraventricular flow seems to originate during the isovolumetric relaxation with a propagation of blood from base to apex. With the E-wave, rapid inflow and vortex formation occurred on both sides of the valve basally. During diastasis the flow gathers in a large vortex before the pattern from the E-wave repeats during the A-wave. In isovolumetric contraction, the flow again gathers in a large vortex that seems to facilitate the flow out in the aorta during systole. No signs of a persistent systolic vortex were visualized. The geometry of the left ventricle and the movement of the AV-plane is important in creating vortices that are favorable for the blood flow and facilitate outflow. The quantitative measurements are in concordance with these findings, but the clinical interpretation must be evaluated in future clinical studies.

Physiological significance of pre- and post-ejection left ventricular tissue velocities and relations to mitral and aortic valve closures.

BACKGROUND: Tissue Doppler shows short duration velocity spikes during pre- and post-ejection (protodiastole). They have been assumed to be isovolumic contraction and relaxation movements, but this is not in accordance with newer studies. METHODS: We examined 22 healthy volunteers. Valve closures and openings were determined from spectral Doppler from LVOT and mitral inflow and transferred to colour tissue Doppler recordings for comparison with tissue velocities, colour M-mode and strain rate (SR). RESULTS: Pre-ejection positive velocity spikes were simultaneous in both walls, starting ca. 24.8 ± 10.1 ms after start QRS, duration 51.5 ± 10.8 ms, ending 10.2 ± 11.5 ms after mitral valve closure (MVC) (p < 0.001). There were corresponding colour tracings and negative strain rate. Protodiastolic lengthening was predominant in the septum. Negative velocity spikes had a duration of 35.5 ± 10.7 ms, ending 9.5 ± 14.7 ms after aortic valve closure (AVC, p < 0.001) in septum. During isovolumic relaxation, strain rate showed apical lengthening (Peak SR-0.72 ± 0.50 s-1 ) and basal shortening (Peak SR 0.44 ± 0.63 s-1 ). CONCLUSION: Electromechanical activation of the LV is simultaneous in septum and lateral wall, occurs before MVC, is terminated by MVC itself and is thus not isovolumic. Protodiastole is a short event of lengthening, predominantly in the septum. It may be the mechanism for valve closure and ends by AVC itself. Isovolumic relaxation occurs after this velocity spike, and is characterized by elongation of the apex, shortening of the base, thus showing a volume shift from base towards apex.

3D Myocardial Mechanical Wave Measurements: Toward In Vivo 3D Myocardial Elasticity Mapping.

OBJECTIVES: This study aimed to investigate the potential of a novel 3-dimensional (3D) mechanical wave velocity mapping technique, based on the natural mechanical waves produced by the heart itself, to approach a noninvasive 3D stiffness mapping of the left ventricle. BACKGROUND: Myocardial fibrosis is recognized as a pathophysiological substrate of major cardiovascular disorders such as cardiomyopathies and valvular heart disease. As fibrosis leads to increased myocardial stiffness, ultrasound elastography measurements could provide important clinical information. METHODS: A 3D high frame rate imaging sequence was implemented on a high-end clinical ultrasound scanner to achieve 820 volumes/s when gating over 4 consecutive cardiac cycles. Five healthy volunteers and 10 patients with various degrees of aortic stenosis were included to evaluate feasibility and reproducibility. Mechanical waves were detected using the novel Clutter Filter Wave Imaging approach, shown to be highly sensitive to the weak tissue displacements caused by natural mechanical waves. RESULTS: 3D spatiotemporal maps of mechanical wave velocities were produced for all subjects. Only the specific mechanical wave at atrial contraction provided a full 3D coverage of the left ventricle (LV). The average atrial kick propagation velocity was 1.6 ± 0.2 m/s in healthy volunteers and 2.8 ± 0.8 m/s in patients (p = 0.0016). A high correlation was found between mechanical wave velocity and age (R2 = 0.88, healthy group), septal wall thickness (R2 = 0.73, entire group), and peak jet velocity across the aortic valve (R2 = 0.70). For 3 of the patients, the higher mechanical wave velocity coexisted with the presence of late gadolinium enhancement on cardiac magnetic resonance. CONCLUSIONS: In this study, 3D LV mechanical wave velocities were visualized and measured in healthy volunteers and patients with aortic stenosis. The proposed imaging sequence and measurement technique allowed, for the first time, the measurement of full spatiotemporal 3D elasticity maps of the LV using ultrasound. (Ultrasonic markers for myocardial fibrosis and prognosis in aortic stenosis; NCT03422770).

Effect of exercise training for five years on all cause mortality in older adults-the Generation 100 study: randomised controlled trial.

OBJECTIVE: To evaluate the effect of five years of supervised exercise training compared with recommendations for physical activity on mortality in older adults (70-77 years). DESIGN: Randomised controlled trial. SETTING: General population of older adults in Trondheim, Norway. PARTICIPANTS: 1567 of 6966 individuals born between 1936 and 1942. INTERVENTION: Participants were randomised to two sessions weekly of high intensity interval training at about 90% of peak heart rate (HIIT, n=400), moderate intensity continuous training at about 70% of peak heart rate (MICT, n=387), or to follow the national guidelines for physical activity (n=780; control group); all for five years. MAIN OUTCOME MEASURE: All cause mortality. An exploratory hypothesis was that HIIT lowers mortality more than MICT. RESULTS: Mean age of the 1567 participants (790 women) was 72.8 (SD 2.1) years. Overall, 87.5% of participants reported to have overall good health, with 80% reporting medium or high physical activity levels at baseline. All cause mortality did not differ between the control group and combined MICT and HIIT group. When MICT and HIIT were analysed separately, with the control group as reference (observed mortality of 4.7%), an absolute risk reduction of 1.7 percentage points was observed after HIIT (hazard ratio 0.63, 95% confidence interval 0.33 to 1.20) and an absolute increased risk of 1.2 percentage points after MICT (1.24, 0.73 to 2.10). When HIIT was compared with MICT as reference group an absolute risk reduction of 2.9 percentage points was observed (0.51, 0.25 to 1.02) for all cause mortality. Control participants chose to perform more of their physical activity as HIIT than the physical activity undertaken by participants in the MICT group. This meant that the controls achieved an exercise dose at an intensity between the MICT and HIIT groups. CONCLUSION: This study suggests that combined MICT and HIIT has no effect on all cause mortality compared with recommended physical activity levels. However, we observed a lower all cause mortality trend after HIIT compared with controls and MICT. TRIAL REGISTRATION: ClinicalTrials.gov NCT01666340.

Left ventricular longitudinal shortening: relation to stroke volume and ejection fraction in ageing, blood pressure, body size and gender in the HUNT3 study.

BACKGROUND: Aims of this cross-sectional study were to assess: the relative contribution of left ventricular (LV) systolic long-axis shortening (mean mitral annular plane systolic excursion, MAPSE) to stroke volume (SV), the mechanisms for preserved ejection fraction (EF) despite reduced MAPSE, the age dependency of myocardial volume and myocardial systolic compression. METHODS: Linear dimensions and longitudinal and cross-sectional M-modes were acquired in 1266 individuals without history of heart disease, diabetes or known hypertension from the third wave of the Nord-Trøndelag Health Study. Measurements were entered into a half-ellipsoid LV model for volume calculations, and volumes were related to age, body size (body surface area, BSA), sex and blood pressure (BP). RESULTS: Mean BP and proportion with hypertensive values increased with increasing age. MAPSE contributed to 75% of SV, with no relation to age or BSA as both MAPSE and SV decreased with increasing age. LV end-diastolic volume (LVEDV) and SV increased with BSA and decreased with higher age; EF was not related to age or BSA. Myocardial volume increased with higher age and BSA, with an additional gender dependency. The association of age with myocardial volume was not significant when corrected for BP, while both systolic and diastolic BP were significant associated with myocardial volume. Myocardial compression was less than 3%. CONCLUSIONS: MAPSE contributes approximately 75% and short axis shortening 25% to SV. Both decline with age, but their percentage contributions to SV are unchanged. EF is preserved by the simultaneous decrease in LVEDV and SV. Myocardial volume is positively associated with age, but this is only related to higher BP, which may have implications for BP treatment in ageing. The myocardium is near incompressible.

Detection of Tissue Fibrosis using Natural Mechanical Wave Velocity Estimation: Feasibility Study.

In the feasibility study described here, we developed and tested a novel method for mechanical wave velocity estimation for tissue fibrosis detection in the myocardium. High-frame-rate ultrasound imaging and a novel signal processing method called clutter filter wave imaging was used. A mechanical wave propagating through the left ventricle shortly after the atrial contraction was measured in the three different apical acquisition planes, for 20 infarct patients and 10 healthy controls. The results obtained were correlated with fibrosis locations from magnetic resonance imaging, and a sensitivity ≥60% was achieved for all infarcts larger than 10% of the left ventricle. The stability of the wave through several heart cycles was assessed and found to be of high quality. This method therefore has potential for non-invasive fibrosis detection in the myocardium, but further validation in a larger group of subjects is needed.

Left ventricular diastolic function: Effects of high-intensity exercise after acute myocardial infarction.

OBJECTIVES: Reduced left ventricular (LV) diastolic function indicates poor prognosis after acute myocardial infarction (AMI). Our aim was to study whether a twelve-week high-intensity interval training program could improve diastolic function in patients with a relatively recent AMI. DESIGN: Twenty-eight patients (mean age 56 (SD 8) years) with a recent AMI performed high-intensity interval training twice a week for 12 weeks. Each training session consisted of four 4-minute bouts at 85%-95% of peak heart rate, separated by 4-minute active breaks. A cardiopulmonary exercise test was performed to determine peak oxygen uptake (VO2peak ). Echocardiography was performed at rest and during an upright bicycle exercise test. RESULTS: There was a significant increase in mitral annulus early diastolic velocity (e') at peak exercise (75 W) from baseline to follow-up (7.9 (1.5) vs. 8.4 (1.7) cm/s, P = .012), but no change in e' at rest (7.1 (1.9) vs. 7.3 (1.7) cm/s, P = .42). There was a significant increase in VO2peak (mean (SD), 35.2 (7.3) vs. 38.9 (7.4) ml/kg/min, P < .001). e' at peak exercise correlated with VO2peak both at baseline and follow-up (r = 0.50, P = .007, and r = 0.41, P = .032). CONCLUSION: The present study shows that LV diastolic function during exercise is related to VO2peak . We also found an improvement of diastolic function after exercise training, even in a population with a relatively well preserved systolic and diastolic function. The results demonstrate the importance of obtaining measurements during exercise when evaluating the effects of exercise interventions.

Over all variability of mitral annular plane peak systolic velocity and peak global longitudinal strain rate in relation to age, body size, and sex: The HUNT Study.

BACKGROUND: Left ventricular (LV) systolic global function can be assessed by peak annular systolic velocity S'. Global longitudinal strain rate (GLSR) is relative LV shortening rate, equivalent to normalizing S' for LV length (S'n ). It has previously been shown that mitral annular plane systolic excursion (MAPSE) and global longitudinal strain (GLS) have similar biological variability, but GLS normalizes for one dimension only, inducing a systematic error, increasing body size dependence. The objective of this study was to compare S' with GLSR in the same way, comparing biological variability and body size dependence. METHODS AND RESULTS: A total of 1266 subjects from the third wave of Nord-Trøndelag Health Study (HUNT), without evidence of heart disease, were examined. Strain rate, S' and wall lengths were measured in the four walls of the two- and four-chamber views. Mean S' was 8.4 (1.4) cm/s, (S'n ) was 0.7 (0.14)s-1 and GLSR 1.02 (0.14)s-1 . All measures declined with age. Normalization of mitral annular velocities for LV length, or the use of GLSR, did not reduce overall biological variability compared with S'. S' did show a weak, positive correlation to BSA, while S'n and GLSR a slightly stronger, negative correlation to BSA. CONCLUSIONS: S', S'n , and GLSR have similar biological variability, which is mainly due to age, not body size variation. Normalizing S' for LV length (as in Sn or GLSR) reverses correlation with BSA inducing a systematic error, due to the one-dimensional normalization for one dimension only.

Left Atrial Volume, Cardiorespiratory Fitness, and Diastolic Function in Healthy Individuals: The HUNT Study, Norway.

Background Left atrial (LA) size and cardiorespiratory fitness (CRF) are predictors of future cardiovascular events in high-risk populations. LA dilatation is a diagnostic criterion for left ventricular diastolic dysfunction. However, LA is dilated in endurance athletes with high CRF, but little is known about the association between CRF and LA size in healthy, free-living individuals. We hypothesized that in a healthy population, LA size was associated with CRF and leisure-time physical activity, but not with echocardiographic indexes of left ventricular diastolic dysfunction. Methods and Results In this cross-sectional study from HUNT (Nord-Trøndelag Health Study), 107 men and 138 women, aged 20 to 82 years, without hypertension, cardiovascular, pulmonary, or malignant disease participated. LA volume was assessed by echocardiography and indexed to body surface area LAVI (left atrial volume index). CRF was measured as peak oxygen uptake (VO2peak) using ergospirometry, and percent of age- and-sex-predicted VO2peak was calculated. Indexes of left ventricular diastolic dysfunction were assessed in accordance with latest recommendations. LAVI was >34 mL/m2 in 39% of participants, and LAVI was positively associated with VO2peak and percentage of age- and-sex-predicted VO2peak (ß [95% CI], 0.11 [0.06-0.16] and 0.18 [0.09-0.28], respectively) and weighted minutes of physical activity per week (ß [95% CI], 0.01 [0.003-0.015]). LAVI was not associated with other indexes of left ventricular diastolic dysfunction. There was an effect modification between age and VO2peak/percentage of age- and-sex-predicted VO2peak showing higher LAVI with advanced age and higher VO2peak/percentage of age- and-sex-predicted VO2peak as presented in prediction diagrams. Conclusions Interpretation of LAVI as a marker of diastolic dysfunction should be done in relation to age-relative CRF. Studies on the prognostic value of LAVI in fit subpopulations are needed.

Baseline and Exercise Predictors of V˙O2peak in Systolic Heart Failure Patients: Results from SMARTEX-HF.

PURPOSE: This study aimed to investigate baseline, exercise testing, and exercise training-mediated predictors of change in peak oxygen uptake (V˙O2peak) from baseline to 12-wk follow-up (ΔV˙O2peak) in a post hoc analysis from the SMARTEX Heart Failure trial. METHODS: We studied 215 patients with heart failure with left ventricular ejection fraction (LVEF) ≤35%, and New York Heart Association (NYHA) classes II-III who were randomized to either supervised high-intensity interval training with exercise target intensity of 90%-95% of peak heart rate (HRpeak) or supervised moderate continuous training (MCT) with target intensity of 60%-70% of HRpeak, or who received a recommendation of regular exercise on their own. Predictors of ΔV˙O2peak were assessed in two models: a logistic regression model comparing highest and lowest tertiles (baseline parameters) and a multivariate linear regression model (test/training/clinical parameters). RESULTS: The change in V˙O2peak in response to the interventions (ΔV˙O2peak) varied substantially, from -8.50 to +11.30 mL·kg·min. Baseline NYHA (class II gave higher odds vs III; odds ratio (OR), 7.1 (2.0-24.9); P = 0.002), LVEF (OR per percent, 1.1 (1.0-1.2); P = 0.005), and age (OR per 10 yr, 0.5 (0.3-0.8); P = 0.003) were associated with ΔV˙O2peak.In the multivariate linear regression, 34% of the variability in ΔV˙O2peak was explained by the increase in exercise training workload, ΔHRpeak between baseline and 12-wk posttesting, age, and ever having smoked. CONCLUSION: Exercise training response (ΔV˙O2peak) correlated negatively with age, LVEF, and NYHA class. The ability to increase workload during the training period and increased ΔHRpeak between baseline and the 12-wk test were associated with a positive outcome.

Left ventricular global strains by linear measurements in three dimensions: interrelations and relations to age, gender and body size in the HUNT Study.

Background: Strain is a relative deformation and has three dimensions, in the left ventricle (LV) usually longitudinal (εL), transmural (εT) and circumferential (εC) strain. All three components can be measured generically by the basic systolic and diastolic dimension measures of LV wall length, wall thickness and diameter. In this observational study we aimed to study the relations of normal generic strains to age, body size and gender, as well as the interrelations between the three strain components. Methods: Generic strains derived from dimension measures by longitudinal and cross-sectional M-mode in all three dimensions were measured in 1266 individuals without heart disease from the Nord-Trøndelag Health Study. Results: The mean εL was -16.3%, εC was -22.7% and εT was 56.5%. Normal values by age and gender are provided. There was a gradient of εC from the endocardial, via the midwall to the external level, lowest at the external. All strains decreased in absolute values by increasing body surface area (BSA) and age, relations were strongest for εL. Gender differences were mainly a function of BSA differences. The three strain components were strongly interrelated through myocardial incompressibility. Conclusions: Global systolic strain is the total deformation of the myocardium; the three strain components are the spatial coordinates of this deformation, irrespective of the technology used for measurement. Normal values are method-dependent and not normative across methods. Interrelation of strains indicates a high degree of myocardial incompressibility and that longitudinal strain carries most of the total information.

Normal ranges for automatic measurements of tissue Doppler indices of mitral annular motion by echocardiography. Data from the HUNT3 Study.

BACKGROUND: Automatic quantification of left ventricular (LV) function could enhance workflow for cardiologists and assist inexperienced clinicians who perform focused cardiac ultrasound. We have developed an algorithm for automatic measurements of the mitral annular plane systolic excursion (MAPSE) and peak velocities in systole (S') and early (e') and late (a') diastole. We aimed to establish normal reference values for the automatic measurements and to compare them with manual measurements. METHODS AND RESULTS: Healthy participants (n = 1157, 52.5% women) from the HUNT3 cross-sectional population study in Norway were included. The mean age ± standard deviation (SD) was 49 ± 14 (range: 19-89) years. The algorithm measured MAPSE, S', e', and a' from apical 4-chamber color tissue Doppler imaging (cTDI) recordings. The manual measurements were obtained by two echocardiographers, who measured MAPSE by M-mode and the velocities by cTDI. For men and women, age-specific reference values were created for groups (mean ± 1.96SD) and by linear regression (mean, 95% prediction interval). Age was negatively correlated with MAPSE, S', and e' and positively correlated with a'. There were small differences between genders. Normal reference ranges were created. The coefficients of variation between automatic and manual measurements ranged from 5.5% (S') to 11.7% (MAPSE). CONCLUSION: Normal reference values for automatic measurements of LV function indices are provided. The automatic measurements were in line with the manual measurements. Implementing automatic measurements and comparison with normal ranges in ultrasound scanners can allow for quick and precise interpretation of LV function.

4-D Intracardiac Ultrasound Vector Flow Imaging-Feasibility and Comparison to Phase-Contrast MRI.

In vivo characterization of intracardiac blood velocity vector fields may provide new clinical information but is currently not available for bedside evaluation. In this paper, 4-D vector flow imaging for intracardiac flow assessment is demonstrated using a clinical ultrasound (US) system and a matrix array transducer, without the use of contrast agent. Two acquisition schemes were developed, one for full volumetric coverage of the left ventricle (LA) at 50 vps and a 3-D thick-slice setup with continuous frame acquisition (4000 vps), both utilizing ECG-gating. The 3-D vector velocity estimates were obtained using a novel method combining phase and envelope information. In vitro validation in a rotating tissue-mimicking phantom revealed velocity estimates in compliance with the ground truth, with a linear regression slope of 0.80, 0.77, and 1.03 for the , , and velocity components, and with standard deviations of 2.53, 3.19, and 0.95 cm/s, respectively. In vivo measurements in a healthy LV showed good agreement with PC-MRI. Quantitative analysis of energy loss (EL) and kinetic energy (KE) further showed similar trends, with peak KE at 1.5 and 2.4 mJ during systole and 3.6 and 3.1 mJ for diastole for US and PC-MRI. Similar for EL, 0.15- 0.2 and 0.7 mW was found during systole and 0.6 and 0.7 mW during diastole, for US and PC-MRI, respectively. Overall, a potential for US as a future modality for 4D cardiac vector flow imaging was demonstrated, which will be further evaluated in clinical studies.