Accuracy of Longitudinal Assessment of Visceral Adipose Tissue by Dual-Energy X-Ray Absorptiometry in Children with Obesity.

Background: Increased visceral adipose tissue (VAT) is strongly associated with cardiometabolic risk factors. Accurate quantification of VAT is available through magnetic resonance imaging (MRI), which incurs a significant financial and time burden. We aimed to assess the accuracy of dual-energy X-ray absorptiometry- (DXA-) derived VAT (DXA-VAT) against a gold standard MRI protocol (MRI-VAT) in children with normal weight and obesity cross-sectionally, and over the course of a lifestyle intervention. Methodology: MRI-VAT and DXA-VAT were quantified in 61 children (30 normal weight and 31 with obesity) at baseline. Children with obesity entered a three-month exercise and/or nutrition intervention after which VAT was reassessed. MRI- and DXA-VAT cross-sectional area, volume, and mass were quantified, and associations were calculated at baseline (n = 61) and pre-post intervention (n = 28, 3 participants dropped out). Method agreement was assessed through Bland-Altman analysis, linear regression, and Passing-Bablok regression. Results: At baseline, all DXA- and MRI-VAT outcomes were strongly associated (r = 0.90, P < 0.001). However, there were no significant associations between absolute or relative change in DXA- and MRI-VAT outcomes (r = 0.25-0.36, P > 0.05). DXA significantly overestimated VAT CSA (cross-sectional area), volume, and mass when compared with MRI (P < 0.001) at baseline. Significant proportional bias was observed for all DXA-VAT outcomes at baseline and for relative longitudinal changes in DXA-VAT. Conclusions: Although DXA-VAT outcomes were strongly associated with MRI-VAT outcomes at baseline, estimates were subject to proportional bias in children with obesity and normal weight. DXA lacks validity for detecting changes in VAT among children with obesity. This trial is registered with NCT01991106.

Effect of High Intensity Interval Training on Cardiac Function in Children with Obesity: A Randomised Controlled Trial.

BACKGROUND: High intensity interval training (HIIT) confers superior cardiovascular health benefits to moderate intensity continuous training (MICT) in adults and may be efficacious for improving diminished cardiac function in obese children. The aim of this study was to compare the effects of HIIT, MICT and nutrition advice interventions on resting left ventricular (LV) peak systolic tissue velocity (S') in obese children. METHODS: Ninety-nine obese children were randomised into one of three 12-week interventions, 1) HIIT [n = 33, 4 × 4 min bouts at 85-95% maximum heart rate (HRmax), 3 times/week] and nutrition advice, 2) MICT [n = 32, 44 min at 60-70% HRmax, 3 times/week] and nutrition advice, and 3) nutrition advice only (nutrition) [n = 34]. RESULTS: Twelve weeks of HIIT and MICT were equally efficacious, but superior to nutrition, for normalising resting LV S' in children with obesity (estimated mean difference 1.0 cm/s, 95% confidence interval 0.5 to 1.6 cm/s, P < 0.001; estimated mean difference 0.7 cm/s, 95% confidence interval 0.2 to 1.3 cm/s, P = 0.010, respectively). CONCLUSIONS: Twelve weeks of HIIT and MICT were superior to nutrition advice only for improving resting LV systolic function in obese children.

Effect of High-Intensity Interval Training on Fitness, Fat Mass and Cardiometabolic Biomarkers in Children with Obesity: A Randomised Controlled Trial.

BACKGROUND: Paediatric obesity significantly increases the risk of developing cardiometabolic diseases across the lifespan. Increasing cardiorespiratory fitness (CRF) could mitigate this risk. High-intensity interval training (HIIT) improves CRF in clinical adult populations but the evidence in paediatric obesity is inconsistent. OBJECTIVES: The objectives of this study were to determine the efficacy of a 12-week, HIIT intervention for increasing CRF and reducing adiposity in children with obesity. METHODS: Children with obesity (n = 99, 7-16 years old) were randomised into a 12-week intervention as follows: (1) HIIT [n = 33, 4 × 4-min bouts at 85-95% maximum heart rate (HRmax), interspersed with 3 min of active recovery at 50-70% HRmax, 3 times/week] and nutrition advice; (2) moderate-intensity continuous training (MICT) [n = 32, 44 min at 60-70% HRmax, 3 times/week] and nutrition advice; and (3) nutrition advice only (nutrition) [n = 34]. CRF was quantified through a maximal exercise test ([Formula: see text]) while adiposity was assessed using magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry (DXA) and air-displacement plethysmography. RESULTS: HIIT stimulated significant increases in relative [Formula: see text] compared with MICT (+3.6 mL/kg/min, 95% CI 1.1-6.0, P = 0.004) and the nutrition intervention (+5.4 mL/kg/min, 95% CI 2.9-7.9, P = 0.001). However, the intervention had no significant effect on visceral and subcutaneous adipose tissue, whole body composition or cardiometabolic biomarkers (P > 0.05). CONCLUSION: A 12-week, HIIT intervention was highly effective in increasing cardiorespiratory fitness when compared with MICT and nutrition interventions. While there were no concomitant reductions in adiposity or blood biomarkers, the cardiometabolic health benefit conferred through increased CRF should be noted. CLINICAL TRIALS REGISTRATION NUMBER: Clinicaltrials.gov; NCT01991106.

Left ventricular morphology and function in adolescents: Relations to fitness and fatness.

BACKGROUND: Obesity in childhood predisposes individuals to cardiovascular disease and increased risk of premature all-cause mortality. The aim of this study was to determine differences in LV morphology and function in obese and normal-weight adolescents. Furthermore, relationships between LV outcomes, cardiorespiratory fitness (CRF) and adiposity were explored. METHODS: LV morphology was assessed using magnetic resonance imaging (MRI) in 20 adolescents (11 normal-weight [BMI equivalent to 18kg/m2-25kg/m2] and 9 obese [BMI equivalent to ≥30kg/m2]); 13.3±1.1years, 45% female, Tanner puberty stage 3 [2-4]) using magnetic resonance imaging (MRI). Global longitudinal strain (GLS), strain rate (SR) and traditional echocardiographic indices were used to assess LV function. CRF (peak oxygen consumption), percent body fat (dual-energy x-ray absorptiometry), abdominal adipose tissue (MRI), and blood biochemistry markers were also evaluated. RESULTS: Adolescents with obesity showed significantly poorer LV function compared to normal-weight adolescents (P<0.05) indicated by higher GLS (+6.29%) and SR in systole (+0.17s-1), and lower SR in early diastole (-0.61s-1), and tissue Doppler velocities (S' -2.7cm/s; e' -2.3cm/s; A' -1.1cm/s). There were no group differences in LV morphology when indexed to fat free mass (P>0.05). Moderate to strong associations between myocardial contractility and relaxation, adiposity, arterial blood pressure and cardiorespiratory fitness were noted (r=0.49-0.71, P<0.05). CONCLUSION: Obesity in adolescence is associated with altered LV systolic and diastolic function. The notable relationship between LV function, CRF and adiposity highlights the potential utility of multidisciplinary lifestyle interventions to treat diminished LV function in this population. CLINICAL TRIAL REGISTRATION: NCT01991106.

Cardiac Amyloidosis Shows Decreased Diastolic Function as Assessed by Echocardiographic Parameterized Diastolic Filling.

Cardiac amyloidosis is a rare but serious condition with poor survival. One of the early findings by echocardiography is impaired diastolic function, even before the development of cardiac symptoms. Early diagnosis is important, permitting initiation of treatment aimed at improving survival. The parameterized diastolic filling (PDF) formalism entails describing the left ventricular filling pattern during early diastole using the mathematical equation for the motion of a damped harmonic oscillator. We hypothesized that echocardiographic PDF analysis could detect differences in diastolic function between patients with amyloidosis and controls. Pulsed-wave Doppler echocardiography of transmitral flow was measured in 13 patients with amyloid heart disease and 13 age- and gender matched controls. E- waves (2 to 3 per subject) were analyzed using in-house developed software. Nine PDF-derived parameters were obtained in addition to conventional echocardiographic parameters of diastolic function. Compared to controls, cardiac amyloidosis patients had a larger left atrial area (23.7 ± 7.5 cm2 vs. 18.5 ± 4.8 cm2, p = 0.04), greater interventricular septum wall thickness (14.4 ± 2.6 mm vs. 9.3 ± 1.3 mm, p < 0.001), lower e' (0.06 ± 0.02 m/s vs. 0.09 ± 0.02 m/s, p < 0.001) and higher E/e' (18.0 ± 12.9 vs. 7.7 ± 1.3, p = 0.001). The PDF parameter peak resistive force was greater in cardiac amyloidosis patients compared to controls (17.9 ± 5.7 mN vs. 13.1 ± 3.1 mN, p = 0.03), and other PDF parameters did not differ. PDF analysis revealed that patients with cardiac amyloidosis had a greater peak resistive force compared to controls, consistent with a greater degree of diastolic dysfunction. PDF analysis may be useful in characterizing diastolic function in amyloid heart disease.

Assessment of the 5-Minute Oxygen Uptake Efficiency Slope in Children With Obesity.

PURPOSE: Poor cardiorespiratory fitness is associated with increased all cause morbidity and mortality. In children with obesity, maximum oxygen uptake (V̇O2max) may not be achieved due to reduced motivation and peripheral fatigue. We aimed to identify a valid submaximal surrogate for V̇O2max in children with obesity. METHOD: Ninety-two children with obesity (7-16 years) completed a maximal exercise treadmill test and entered a three-month exercise and/or nutrition intervention after which the exercise test was repeated (n = 63). Participants were required to reach V̇O2max to be included in this analysis (n = 32 at baseline and n = 13 at both time-points). The oxygen uptake efficiency slope (OUES) was determined as the slope of the line when V̇O2 (L/min) was plotted against log V̇E. Associations between the maximal OUES, submaximal OUES (at 3, 4, 5 and 6 min of the exercise test) and V̇O2max were calculated. RESULTS: In the cross-sectional analysis, V̇O2max (L/min) was strongly correlated with 5-min OUES independent of Tanner puberty stage and sex (R2 = .80, p < .001). Longitudinal changes in V̇O2max were closely reflected by changes in 5-min OUES independent of change in percent body fat (R2 = .63, p < .05). CONCLUSION: The 5-min OUES is a viable alternative to V̇O2max when assessing children with obesity.

Effects of exercise intensity and nutrition advice on myocardial function in obese children and adolescents: a multicentre randomised controlled trial study protocol.

INTRODUCTION: The prevalence of paediatric obesity is increasing, and with it, lifestyle-related diseases in children and adolescents. High-intensity interval training (HIIT) has recently been explored as an alternate to traditional moderate-intensity continuous training (MICT) in adults with chronic disease and has been shown to induce a rapid reversal of subclinical disease markers in obese children and adolescents. The primary aim of this study is to compare the effects of HIIT with MICT on myocardial function in obese children and adolescents. METHODS AND ANALYSIS: Multicentre randomised controlled trial of 100 obese children and adolescents in the cities of Trondheim (Norway) and Brisbane (Australia). The trial will examine the efficacy of HIIT to improve cardiometabolic outcomes in obese children and adolescents. Participants will be randomised to (1) HIIT and nutrition advice, (2) MICT and nutrition advice or (3) nutrition advice. Participants will partake in supervised exercise training and/or nutrition sessions for 3 months. Measurements for study end points will occur at baseline, 3 months (postintervention) and 12 months (follow-up). The primary end point is myocardial function (peak systolic tissue velocity). Secondary end points include vascular function (flow-mediated dilation assessment), quantity of visceral and subcutaneous adipose tissue, myocardial structure and function, body composition, cardiorespiratory fitness, autonomic function, blood biochemistry, physical activity and nutrition. Lean, healthy children and adolescents will complete measurements for all study end points at one time point for comparative cross-sectional analyses. ETHICS AND DISSEMINATION: This randomised controlled trial will generate substantial information regarding the effects of exercise intensity on paediatric obesity, specifically the cardiometabolic health of this at-risk population. It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT on subclinical markers of disease. TRIAL REGISTRATION NUMBER: NCT01991106.

Left atrial size--another differentiator for cardiac amyloidosis.

BACKGROUND: The "sparkled" echocardiographic appearance of amyloid has become less visually obvious in the era of harmonic imaging. Significantly dilated atria in the setting of a normal sized ventricle may be another easy visual marker for cardiac amyloidosis. METHODS: A retrospective analysis of echocardiograms of patients with biopsy-proven cardiac amyloid compared with patients with hypertension was conducted. There were 36 patients in each group, and they were matched for left ventricular wall thickness, as well as age and sex. RESULTS: Patients with cardiac amyloid had significantly larger atria than the group with hypertension (left atrial areas 29 cm(2) versus 19 cm(2), p<0.001, AUC 0.84, volumes 100 cm(3) versus 55 cm(3), p<0.001, AUC 0.915). A volume of 69 cm(3) produced a specificity and sensitivity of 85% for amyloidosis. CONCLUSIONS: Atrial dilatation can be used as a visual marker for cardiac amyloidosis. This may be a simple visual method to differentiate this infiltrative cardiomyopathy from left ventricular hypertrophy.

Chronic non-transmural infarction has a delayed recovery of function following revascularization.

BACKGROUND: The time course of regional functional recovery following revascularization with regards to the presence or absence of infarction is poorly known. We studied the effect of the presence of chronic non-transmural infarction on the time course of recovery of myocardial perfusion and function after elective revascularization. METHODS: Eighteen patients (mean age 69, range 52-84, 17 men) prospectively underwent cine magnetic resonance imaging (MRI), delayed contrast enhanced MRI and rest/stress 99m-Tc-tetrofosmin single photon emission computed tomography (SPECT) before, one and six months after elective coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). RESULTS: Dysfunctional myocardial segments (n = 337/864, 39%) were classified according to the presence (n = 164) or absence (n = 173) of infarction. Infarct transmurality in dysfunctional segments was largely non-transmural (transmurality = 31 +/- 22%). Quantitative stress perfusion and wall thickening increased at one month in dysfunctional segments without infarction (p < 0.001), with no further improvement at six months. Despite improvements in stress perfusion at one month (p < 0.001), non-transmural infarction displayed a slower and lesser improvement in wall thickening at one (p < 0.05) and six months (p < 0.001). CONCLUSIONS: Dysfunctional segments without infarction represent repetitively stunned or hibernating myocardium, and these segments improved both perfusion and function within one month after revascularization with no improvement thereafter. Although dysfunctional segments with non-transmural infarction improved in perfusion at one month, functional recovery was mostly seen between one and six months, possibly reflecting a more severe ischemic burden. These findings may be of value in the clinical assessment of regional functional recovery in the time period after revascularization.

Age and gender specific normal values of left ventricular mass, volume and function for gradient echo magnetic resonance imaging: a cross sectional study.

BACKGROUND: Knowledge about age-specific normal values for left ventricular mass (LVM), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) by cardiac magnetic resonance imaging (CMR) is of importance to differentiate between health and disease and to assess the severity of disease. The aims of the study were to determine age and gender specific normal reference values and to explore the normal physiological variation of these parameters from adolescence to late adulthood, in a cross sectional study. METHODS: Gradient echo CMR was performed at 1.5 T in 96 healthy volunteers (11-81 years, 50 male). Gender-specific analysis of parameters was undertaken in both absolute values and adjusted for body surface area (BSA). RESULTS: Age and gender specific normal ranges for LV volumes, mass and function are presented from the second through the eighth decade of life. LVM, ESV and EDV rose during adolescence and declined in adulthood. SV and EF decreased with age. Compared to adult females, adult males had higher BSA-adjusted values of EDV (p = 0.006) and ESV (p < 0.001), similar SV (p = 0.51) and lower EF (p = 0.014). No gender differences were seen in the youngest, 11-15 year, age range. CONCLUSION: LV volumes, mass and function vary over a broad age range in healthy individuals. LV volumes and mass both rise in adolescence and decline with age. EF showed a rapid decline in adolescence compared to changes throughout adulthood. These findings demonstrate the need for age and gender specific normal ranges for clinical use.

Physiological determinants of the variation in left ventricular mass from early adolescence to late adulthood in healthy subjects.

BACKGROUND: The physiological determinants of left ventricular mass (LVM) measured by cardiac magnetic resonance (CMR) imaging are not well defined as prior investigators have studied either adults or adolescents in isolation or have not strictly excluded hypertension or accounted for the effects of exercise habits, haemodynamic, demographic, or body shape characteristics. METHODS: Ninety-seven healthy volunteers (11-81 years, 51 males) underwent CMR. All parameters [unstandardized and adjusted for body surface area (BSA)] were analysed according to gender and by adolescence versus adulthood (adolescents<20 years, adults>or=20 years). The influence of haemodynamic factors, exercise and demographic factors on LVM were determined with multivariate linear regression. RESULTS: Left ventricular mass rose during adolescence and declined in adulthood. LVM and LVMBSA were higher in males both in adults (LVM: 188+/-22 versus 140+/-21 g, P<0.001; LVMBSA: 94+/-11 versus 80+/-11 g m(-2), P<0.001) and in adolescents when adjusted for BSA (LVM: 128+/-29 versus 107+/-20 g, P=0.063; LVMBSA: 82+/-8 versus 71+/-10 g m(-2), P=0.025). In adults, systolic blood pressure (SBP) and self-reported physical activity increased while meridional and circumferential wall stress were constant with age. Multivariate regression analysis revealed age, gender and BSA as the major determinants of LVM (global R2=0.68). CONCLUSIONS: Normal LVM shows variation over a broad age range in both genders with a rise in adolescence and subsequent decline with increasing age in adulthood despite an increase in SBP and physical activity. BSA, age and gender were found to be major contributors to the variation in LVM in healthy adults, while haemodynamic factors, exercise and wall stress were not.

Physiological determinants of the variation in left ventricular mass from early adolescence to late adulthood in healthy subjects.

BACKGROUND: The physiological determinants of left ventricular mass (LVM) measured by cardiac magnetic resonance (CMR) imaging are not well defined as prior investigators have studied either adults or adolescents in isolation or have not strictly excluded hypertension or accounted for the effects of exercise habits, haemodynamic, demographic, or body shape characteristics. METHODS: A total of 102 healthy volunteers (12-81 years, 53 males) underwent CMR. All parameters [unstandardized and adjusted for body surface area (BSA)] were analysed according to gender and by adolescence versus adulthood (adolescents <20 years, adults > or = 20 years). The influence of haemodynamic factors, exercise, and demographic factors on LVM were determined with multivariate linear regression. RESULTS: LVM rose during adolescence and declined in adulthood. LVM and LVMBSA were higher in males both in adults (LVM: 188 +/- 22 g versus 139 +/- 21 g, P < 0.001; LVMBSA: 94 +/- 11 g m(-2) versus 80 +/- 11 g m(-2), P < 0.001) and in adolescents when adjusted for BSA (LVM: 128 +/- 29 g versus 107 +/- 20 g, P = 0.063; LVMBSA: 82 +/- 8 g m(-2) versus 71 +/- 10 g m(-2), P = 0.025). In adults, systolic blood pressure (SBP) and self-reported physical activity increased while meridional and circumferential wall stress were constant with age. Multivariate regression analysis revealed age, gender, and BSA as the major determinants of LVM (global R2 = 0.69). CONCLUSIONS: Normal LVM shows variation over a broad age range in both genders with a rise in adolescence and subsequent decline with increasing age in adulthood despite an increase in SBP and physical activity. BSA, age, and gender were found to be major contributors to the variation in LVM in healthy adults, while haemodynamic factors, exercise, and wall stress were not.

Infarct transmurality and adjacent segmental function as determinants of wall thickening in revascularized chronic ischemic heart disease.

BACKGROUND: There are many factors which influence regional left ventricular wall thickening (WT) in ischemic heart disease (IHD). We used magnetic resonance imaging (MRI) to explore, in patients with chronic ischemic heart disease (CIHD), how regional WT is affected by both infarct transmurality (IT) and the function of adjacent segments. We also compared these findings with a group of healthy volunteers (controls). METHODS: Twenty patients (20 men, mean age 63, range 45-80 years) were imaged with cine MRI for function and delayed enhancement MRI for infarction 6 months after revascularization. Twenty age and sex matched controls underwent cine MRI. Short-axis images were analysed using a 12-segment per slice model in four midventricular slices per subject. RESULTS: WT and IT were inversely related (r(2) = 0.11, P<0.001). WT of non-infarcted segments in patients was lower than corresponding segments in controls (5.1 versus 4.6 mm, P<0.001). WT in patients decreased with an increasing number of dysfunctional adjacent segments (P<0.001) and increasing IT (P<0.001). WT was more strongly influenced by the number of dysfunctional adjacent segments (t = -22.93, P<0.001) than by IT (t = -4.50, P<0.001). CONCLUSIONS: The number of dysfunctional adjacent segments is a greater determinant than infarct transmurality on regional wall thickening.

Quantitative polar representation of left ventricular myocardial perfusion, function and viability using SPECT and cardiac magnetic resonance: initial results.

BACKGROUND: The clinical management of patients with coronary artery disease (CAD) often involves a complex assessment of the extent and severity of changes in left ventricular (LV) myocardial perfusion, function and viability. We aimed to explore the feasibility of integrative quantitative representation of LV perfusion, function and viability in adjacent polar plots. In order to assess the clinical usefulness of the quantitative methods, we also explored the relationship and determined the agreement between visual scoring and quantitative measurement of regional perfusion and function. METHODS: Ten patients with CAD underwent rest and stress (99m)Tc-tetrofosmin single photon emission computed tomography (SPECT) and cardiac magnetic resonance (CMR) imaging. Software was developed in-house for generating polar plots from semi-automatic quantification of rest and stress perfusion from SPECT, function from cine CMR and viability from delayed contrast enhancement (DE) CMR. The agreement between visual assessment and quantification of both perfusion and function was tested by Kendall's coefficient of concordance (W). RESULTS: Polar plots were created using quantitative data from the semi-automatic analysis of perfusion, function and viability. Kendall's W for agreement between quantitative measurement and visual scoring was 1.0 (P<0.001) for perfusion and 0.85 (P<0.001) for function. CONCLUSIONS: Side-by-side quantitative polar representation of LV perfusion, function and viability is feasible and may aid in the complex assessment of these parameters. The agreement between quantitative measurement and visual scoring was very good for both perfusion and function.

Center of volume and total heart volume variation in healthy subjects and patients before and after coronary bypass surgery.

BACKGROUND: Total heart volume variation (THVV) and center of volume variation (COVV) likely affects the efficiency of cardiac pumping, but no study has determined COVV of the heart throughout the cardiac cycle or the effect of surgery on THVV in adults. Therefore, the purposes of this study were to determine COVV in healthy adults and patients with cardiac failure due to ischemic heart disease (IHD), identify any difference in THVV between these two groups, and determine how these parameters are affected by coronary bypass surgery. METHODS: Six healthy volunteers and eight patients before and after surgery were investigated with cardiovascular magnetic resonance imaging. The atrioventricular plane movement (AVPM), THVV and time resolved three-dimensional coordinates of the center of the cardiac volume (COVV) were measured. RESULTS: COVV followed a loop in 3D space that between the end-points was approximately 2 mm with no difference between healthy subjects and patients before surgery (P = 0.093), although AVPM was significantly lower in patients (P = 0.002). However, after surgery the COVV during the cardiac cycle doubled (P = 0.012) and the increase in THVV was significant (P = 0.050), although of very small magnitude, and the AVPM remained unchanged (P = 0.401). CONCLUSION: COVV and THVV were similar in patients and healthy subjects even though AVPM was lower in the patient population. After surgery, however, COVV doubled despite a very small change in THVV and no change in AVPM. Taken together, the results of this study may provide new insights into the energy expenditure and efficiency of cardiac pumping.