Håvard Dalen

Segmental and global longitudinal strain and strain rate based on echocardiography of 1266 healthy individuals: the HUNT study in Norway

AIMS To study the distribution of longitudinal systolic strain and strain rate (SR) as indicators of myocardial deformation according to age and sex in a healthy population. METHODS AND RESULTS Longitudinal strain and SR were determined in 1266 healthy individuals from three standard apical views, using a combination of speckle tracking (ST) and tissue Doppler imaging (TDI) to track regions of interest (ROIs). To test applicability of the reference values, we used a subset of the population to compare four methods of assessing myocardial deformation: (1) a combination of TDI and ST; (2) TDI with fixed ROIs; (3) TDI with tracking of ROIs; and (4) ST. Mean (SD) overall global longitudinal strain and SR were -17.4% (2.3) and -1.05 s(-1) (0.13) in women, and -15.9% (2.3) and -1.01 s(-1) (0.13) in men. Deformation indices decreased with increasing age. The combined and ST methods showed identical SR, but values were significantly lower than those obtained by TDI. Strain was overestimated by the ST method (18.4%) compared with the combined method (17.4%). CONCLUSION The reference values for global and segmental longitudinal strain and SR obtained from this population study are applicable for use in a wide clinical setting.

Systematic evaluation of coding variation identifies a candidate causal variant in TM6SF2 influencing total cholesterol and myocardial infarction risk.

Blood lipid levels are heritable, treatable risk factors for cardiovascular disease. We systematically assessed genome-wide coding variation to identify new genes influencing lipid traits, fine map known lipid loci and evaluate whether low-frequency variants with large effects exist for these traits. Using an exome array, we genotyped 80,137 coding variants in 5,643 Norwegians. We followed up 18 variants in 4,666 Norwegians and identified ten loci with coding variants associated with a lipid trait (P < 5 × 10−8). One variant in TM6SF2 (encoding p.Glu167Lys), residing in a known genome-wide association study locus for lipid traits, influences total cholesterol levels and is associated with myocardial infarction. Transient TM6SF2 overexpression or knockdown of Tm6sf2 in mice alters serum lipid profiles, consistent with the association observed in humans, identifying TM6SF2 as a functional gene within a locus previously known as NCAN-CILP2-PBX4 or 19p13. This study demonstrates that systematic assessment of coding variation can quickly point to a candidate causal gene.

Reference Values and Distribution of Conventional Echocardiographic Doppler Measures and Longitudinal Tissue Doppler Velocities in a Population Free From Cardiovascular Disease

Background—This study aimed to investigate the distribution of conventional Doppler measurements, pulsed wave tissue Doppler imaging (pwTDI)- and color tissue Doppler imaging-derived velocities, by age and sex in a healthy population. Methods and Results—Longitudinal tissue Doppler velocities were determined in 1266 healthy individuals from standard apical 4- and 2-chamber views. By the pwTDI method, mean±SD systolic mitral annular velocities were 8.2±1.3 cm/s in women and 8.6±1.4 cm/s in men, and by color tissue Doppler, they were 6.6±1.1 cm/s in women and 6.9±1.3 cm/s in men. With pwTDI, diastolic early mitral annular velocities were 11.8±3.2 cm/s in women and 10.8±3.0 cm/s in men, with corresponding ratios between mitral early flow velocity and early diastolic tissue velocity of 6.7±0.8 in women and 6.4±0.8 in men. By pwTDI, tricuspid annular systolic and early diastolic velocities were 12.5±1.9 and 13.3±3.0, respectively, in women and 12.8±2.2 and 12.5±3.3, respectively, in men. There was a significant decrease in left and right ventricular function with increasing age. Conclusions—The longitudinal mitral and tricuspid annular velocities from this population study are widely applicable as reference values. Reference values for annular velocities should be specified by sex and age. The average of inferoseptal and anterolateral wall velocities may be the preferred index of left ventricular performance.

Reproducibility in echocardiographic assessment of the left ventricular global and regional function, the HUNT study

AIMS The study aimed to compare the inter-observer reproducibility of new and traditional measurements of the left ventricular (LV) global and regional function. METHODS AND RESULTS Two experienced echocardiographers performed 20 complete echo/Doppler examinations and 50 analyses on ten healthy subjects. All recordings were analysed for systolic and diastolic conventional and deformation measurements by both echocardiographers. Inter-observer mean error (absolute difference divided by the mean) was 4% and lowest (P = 0.001) for systolic M-mode annulus excursion. Mean error for the regional deformation indices was significantly higher than for all the global measurements (all P < 0.001). Mean error for analyses of the same recording was 34% (P = 0.002) lower for global systolic indices and 44% (P < 0.001) lower for global diastolic indices than inter-observer mean error for analyses made in separate recordings. CONCLUSION Systolic M-mode annulus excursion showed better inter-observer reproducibility than other traditional and newer measurements of LV systolic and diastolic function. Repeated analyses of the same recordings underestimate the more clinically relevant inter-observer reproducibility by approximately 40% for most measurements of LV function.

High-Intensity Interval Training in Patients with Heart Failure with Reduced Ejection Fraction

Background: Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE). Methods: Two hundred sixty-one patients with left ventricular ejection fraction ⩽35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE. Thereafter, patients were encouraged to continue exercising on their own. Clinical assessments were performed at baseline, after the intervention, and at follow-up after 52 weeks. Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks. Results: Groups did not differ in age (median, 60 years), sex (19% women), ischemic pathogenesis (59%), or medication. Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT (P=0.45); left ventricular end-diastolic diameter changes compared with RRE were −2.8 mm (−5.2 to −0.4 mm; P=0.02) in HIIT and −1.2 mm (−3.6 to 1.2 mm; P=0.34) in MCT. There was also no difference between HIIT and MCT in peak oxygen uptake (P=0.70), but both were superior to RRE. However, none of these changes was maintained at follow-up after 52 weeks. Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks (HIIT, 39%; MCT, 25%; RRE, 34%; P=0.16). Training records showed that 51% of patients exercised below prescribed target during supervised HIIT and 80% above target in MCT. Conclusions: HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity, and its feasibility remains unresolved in patients with heart failure. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046.

Focus cardiac ultrasound: the European Association of Cardiovascular Imaging viewpoint

The concept of point-of-care, problem-oriented focus cardiac ultrasound examination (FoCUS) is increasingly applied in the settings of medical emergencies, including cardiac diseases. The European Association of Cardiovascular Imaging (EACVI) recognizes that cardiologists are not the only medical professionals dealing with cardiovascular emergencies. In reality, emergency cardiac diagnostics and treatment are also carried out by a wide range of specialists. For the benefit of the patients, the EACVI encourages any medical professional, sufficiently trained to obtain valuable information from FoCUS, to use it in emergency settings. These medical professionals need to have the necessary knowledge to understand the obtained information entirely, and to use it correctly, thoughtfully and with care. In this document, the EACVI underlines major differences between echocardiography and FoCUS, and underscores the need for specific education and training in order to fully utilize advantages and minimize drawbacks of this type of cardiac ultrasound examination in the critically ill patients.

Routinely adding ultrasound examinations by pocket-sized ultrasound devices improves inpatient diagnostics in a medical department.

BACKGROUND We aimed to investigate the potential benefit of adding a routine cardiac and abdominal diagnostic examination by pocket-sized ultrasound device in patients admitted to a medical department. METHODS A random sample of 196 patients admitted to the medical department at a non-university hospital in Norway between March and September 2010 was studied. The patients underwent cardiac and abdominal screening with a pocket-sized ultrasound device with B-mode and color flow imaging after a principal diagnosis was set. Three internists/cardiologists experienced in ultrasonography performed the examinations. Diagnostic corrections were made and findings were confirmed by high-end echocardiography and examinations at the radiologic department. RESULTS 196 patients were included (male=56.6%, mean±SD; 68.1±15.0 years old). The time spent doing the ultrasound screening was mean±SD 4.3±1.6 min for the cardiac screening and 2.5±1.1 min for the abdominal screening. In 36 (18.4%) patients this examination resulted in a major change in the primary diagnosis. In 38 (19.4%) patients the diagnosis was verified and in 18 (9.2%) patients an important additional diagnosis was made. CONCLUSION By adding a pocket-sized ultrasound examination of <10 min to usual care, we corrected the diagnosis in almost 1 of 5 patients admitted to a medical department, resulting in a completely different treatment strategy without delay in many of the patients. Routinely adding a cardiac and abdominal ultrasound screening has the potential to rearrange inpatients workflow and diagnosis.

High Intensity Interval Training in Heart Failure Patients with Reduced Ejection Fraction

Background: Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE). Methods: Two hundred sixty-one patients with left ventricular ejection fraction ⩽35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE. Thereafter, patients were encouraged to continue exercising on their own. Clinical assessments were performed at baseline, after the intervention, and at follow-up after 52 weeks. Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks. Results: Groups did not differ in age (median, 60 years), sex (19% women), ischemic pathogenesis (59%), or medication. Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT (P=0.45); left ventricular end-diastolic diameter changes compared with RRE were −2.8 mm (−5.2 to −0.4 mm; P=0.02) in HIIT and −1.2 mm (−3.6 to 1.2 mm; P=0.34) in MCT. There was also no difference between HIIT and MCT in peak oxygen uptake (P=0.70), but both were superior to RRE. However, none of these changes was maintained at follow-up after 52 weeks. Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks (HIIT, 39%; MCT, 25%; RRE, 34%; P=0.16). Training records showed that 51% of patients exercised below prescribed target during supervised HIIT and 80% above target in MCT. Conclusions: HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity, and its feasibility remains unresolved in patients with heart failure. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046.

Cardiovascular Risk Factors and Systolic and Diastolic Cardiac Function: A Tissue Doppler and Speckle Tracking Echocardiographic Study

BACKGROUND The aim of this study was to determine whether blood pressure, body mass index (BMI), serum lipids, glucose, and renal function are associated with left ventricular (LV) and right ventricular function in a low-risk population. METHODS The associations of common risk factors with cardiac function were assessed, using multiple linear regression, in a random sample of 1,266 individuals free from hypertension, diabetes, and cardiovascular disease. A combination of conventional echocardiographic, speckle-tracking, and tissue Doppler methods was used to assess cardiac function. RESULTS Older age and higher BMI, systolic and diastolic blood pressure, and non-high-density lipoprotein (HDL) cholesterol were associated with lower LV function. Thus, LV strain was reduced by approximately 5% per 5 kg/m(2) increase in BMI and by 4% per 10 mm Hg increase in diastolic blood pressure. Corresponding reductions in peak early diastolic mitral annular velocity were 7% for both BMI and diastolic blood pressure. Higher HDL cholesterol was associated with better LV function. In women, smoking was also associated with reduced LV function. LV function was lower also at low levels of diastolic pressure and BMI. Reduced right ventricular function was related to older age, smoking, higher diastolic blood pressure and non-HDL cholesterol, and lower HDL cholesterol. CONCLUSIONS These findings suggest that conventional risk factors may predict cardiac function many years before clinical disease. The J-shaped associations related to diastolic blood pressure and BMI may suggest that in some individuals, low levels of these factors may indicate underlying but unknown disease.

Association of growth differentiation factor 11/8, putative anti-ageing factor, with cardiovascular outcomes and overall mortality in humans: analysis of the Heart and Soul and HUNT3 cohorts

AIMS Growth differentiation factor 11 and/or its homologue growth differentiation factor 8 (GDF11/8) reverses age-related cardiac hypertrophy and vascular ageing in mice. We investigated whether GDF11/8 associates with cardiovascular outcomes, left ventricular hypertrophy (LVH), or age in humans. METHODS AND RESULTS We measured plasma GDF11/8 levels in 928 participants with stable ischaemic heart disease in the Heart and Soul study. We adjudicated heart failure hospitalization, stroke, myocardial infarction, death, and their composite endpoint. Left ventricular hypertrophy was evaluated by echocardiography. We used multivariable Cox proportional hazards models to compare rates of cardiovascular events and death across GDF11/8 quartiles and logistic regression models to evaluate the association between GDF11/8 and LVH. Four hundred and fifty participants (48.5%) experienced a cardiovascular event or death during 8.9 years of follow-up. The adjusted risk of the composite endpoint was lower in the highest compared with the lowest GDF11/8 quartile [hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.33-0.60; P < 0.001]. We replicated this relationship of GDF11/8 to adverse events in 971 participants in the HUNT3 cohort (adjusted HR, 0.34; 95% CI, 0.23-0.51; P < 0.001). Left ventricular hypertrophy was present in 368 participants (39.7%) at baseline. Participants in the highest quartile of GDF11/8 were less likely to have LVH than those in the lowest quartile (adjusted OR, 0.55; 95% CI, 0.35-0.86; P = 0.009). GDF11/8 levels were lower in older individuals (P < 0.001). CONCLUSION In patients with stable ischaemic heart disease, higher GDF11/8 levels are associated with lower risk of cardiovascular events and death. Our findings suggest that GDF11/8 has similar cardioprotective properties in humans to those demonstrated in mice.