Associations of childhood and adult obesity with left ventricular structure and function.

BACKGROUND: Overweight and obesity are associated with left ventricular (LV) dysfunction. We sought whether echocardiographic evidence of abnormal adult cardiac structure and function was related to childhood or adult adiposity. METHODS: This study included 159 healthy individuals aged 7-15 years and followed until age 36-45 years. Anthropometric measurements were performed both at baseline and follow-up. Cardiac structure (indexed left atrial volume (LAVi), left ventricular mass (LVMi)) and LV function (global longitudinal strain (GLS), mitral e') were assessed using standard echocardiography at follow-up. Conventional cutoffs were used to define abnormal LAVi, LVMi, GLS and mitral annular e'. RESULTS: Childhood body mass index (BMI) was correlated with LVMi (r=0.25, P=0.002), and child waist circumference was correlated with LVMi (r=0.18, P=0.03) and LAVi (r=0.20, P=0.01), but neither were correlated with GLS. One s.d. (by age and sex) increase in childhood BMI was associated with LV hypertrophy (relative risk: 2.04 (95% confidence interval (CI): 1.09, 3.78)) and LA enlargement (relative risk: 1.81 (95% CI: 1.02, 3.21)) independent of adult BMI, but the association was not observed with impaired GLS or mitral e'. Cardiac functional measures were more impaired in those who had normal BMI as child, but had high BMI in adulthood (P<0.03), and not different in those who were overweight or obese as a child and remained so in adulthood (P>0.33). CONCLUSIONS: Childhood adiposity is independently associated with structural cardiac disturbances (LVMi and LAVi). However, functional alterations (GLS and mitral e') were more frequently associated with adult overweight or obesity, independent of childhood adiposity.

Growth and geographical variation in the use of cardiac imaging in Australia.

BACKGROUND AND AIM: Growth rates and regional differences in the use of cardiac imaging are potential metrics of quality of care. This study sought to define growth and regional variation in outpatient cardiac imaging in Australia. METHODS: Analyses are based on the rate of outpatient transthoracic echocardiography (TTE), transoesophageal echocardiography (TOE) and stress echocardiography (SE) and single-photon emission computed tomography (SPECT) per 100 000 people in each geographic insurance region in Australia (Medicare local, ML). Numbers of tests from 2002 to 2013 were obtained from Medicare Australia Statistics, and the number of doctors was obtained from the Health Workforce data. Demographic data (total population, rural areas and quintiles of disadvantage) were obtained from census data. RESULTS: Over the past 11 years, TTE reimbursements/100 000 people increased from 1780 to 3497 (8.8% annualised growth), TOE from 33 to 61, SE from 181 to 947 and SPECT from 287 to 337. SE had the biggest increment, an average growth rate of 38.5%/year. The relationships between the use of each cardiac imaging techniques and demographic, medical and illness factors were analysed in outpatient tests reimbursed in 2012. For each additional medical practitioner per 1000 people, there was an increase in the rate of TTE (ß = 1.25 (95% confidence interval CI: 1.17-1.33), P < 0.001), and TOE use (ß = 1.13 (1.04-1.24), P = 0.005), independent of regional burden of cardiovascular disease and social determinants. For SPECT the largest independent correlate for testing was the percentage of women within the ML; each additional percentage increase resulted in doubling of the rate of testing (ß = 2.25 (1.72-2.94), P < 0.001). CONCLUSION: Variation in the use of TTE in Australia does not appear illness related and may be evidence of under- and overutilisation. An appropriate use process may contain this variation.

What is the evidence status of Appropriate Use Criteria (AUC)? Insight from a matching exercise with the guidelines for echocardiography.

There is interest in adapting the American Appropriate Use Criteria (AUC) for transthoracic echocardiography to Australian practice. We matched 90 of 98 AUC with the guidelines (53 appropriate, 12 sometimes appropriate, 25 rarely appropriate), but eight lacked any match. Among the matched criteria, 76 (82%) indications were concordant with the guidelines. A stronger evidence base would be desirable to settle these discrepancies before Australian adoption of AUC.

Chemotherapy-related cardiomyopathy: a neglected aspect of cancer survivorship.

Improvements in survival from cancer have led to a large population who are at risk of late complications of chemotherapy. One of the most serious cardiovascular complications is chemotherapy-related cardiomyopathy (CRC), which may become clinically overt years or even decades after treatment and has over threefold higher mortality rate compared with idiopathic dilated cardiomyopathy. The early stages of this condition appear to respond well to cardioprotective medications (i.e. angiotensin-converting enzyme inhibitors, ß-blockers). Periodic cardiac monitoring is necessary in this population to identify patients who would benefit from treatment. Cardio-oncology clinics have been established in recognition of this hazard in survivorship. This review summarises the epidemiology and pathophysiology of CRC, the evidence base for different non-invasive imaging modalities for screening and diagnosis and the rationale for treatment.

Diagnostic accuracy of heart-rate recovery after exercise in the assessment of diabetic cardiac autonomic neuropathy.

AIMS: Poor prognosis associated with blunted post-exercise heart-rate recovery may reflect autonomic dysfunction. This study sought the accuracy of post-exercise heart-rate recovery in the diagnosis of cardiac autonomic neuropathy, which represents a serious, but often unrecognized complication of Type 2 diabetes. METHODS: Clinical assessment of cardiac autonomic neuropathy and maximal treadmill exercise testing for heart-rate recovery were performed in 135 patients with Type 2 diabetes and negative exercise echocardiograms. Cardiac autonomic neuropathy was defined by abnormalities in ≥ 2 of 7 autonomic function markers, including four cardiac reflex tests and three indices of short-term (5-min) heart-rate variability. Heart-rate recovery was defined at 1-, 2- and 3-min post-exercise. RESULTS: Patients with cardiac autonomic neuropathy (n = 27; 20%) had lower heart-rate recovery at 1-, 2- and 3-min post-exercise (P < 0.01). Heart-rate recovery demonstrated univariate associations with autonomic function markers (r-values 0.20-0.46, P < 0.05). Area under the receiver-operating characteristic curve revealed good diagnostic performance of all heart-rate recovery parameters (range 0.80-0.83, P < 0.001). Optimal cut-offs for heart-rate recovery at 1-, 2- and 3-min post-exercise were ≤ 28 beats/min (sensitivity 93%, specificity 69%), ≤ 50 beats/min (sensitivity 96%, specificity 63%) and ≤ 52 beats/min (sensitivity 70%, specificity 84%), respectively. These criteria predicted cardiac autonomic neuropathy independently of relevant clinical and exercise test information (adjusted odds ratios 7-28, P < 0.05). CONCLUSIONS: Post-exercise heart-rate recovery provides an accurate diagnostic test for cardiac autonomic neuropathy in Type 2 diabetes. The high sensitivity and modest specificity suggests heart-rate recovery may be useful to screen for patients requiring clinical autonomic evaluation.

Reliability of heart rate variability in patients with type 2 diabetes mellitus.

AIMS: Heart rate variability may be used to assess diabetic cardiac autonomic neuropathy. The aim of the present study was to determine the reliability of standard short-term clinical measurements of heart rate variability in patients with Type 2 diabetes. METHODS: In 24 patients with Type 2 diabetes (11 male, age 61 ± 9 years), parameters of heart rate variability in the time domain (standard deviation of RR intervals, coefficient of variation of RR intervals and root mean square of successive RR interval differences) and frequency domain (very low frequency, low frequency, high frequency and total spectral power) were derived from a 5-min electrocardiograph recorded during two laboratory visits separated by 16 ± 8 days. Absolute and relative reliability were assessed by 95% limits of random variation and the intraclass correlation coefficient, respectively. Categorical agreement of classifications of heart rate variability and sample size estimates for clinical trials were calculated. RESULTS: Despite no significant difference in mean heart rate variability between tests, 95% limits of random variation indicated that repeated measurements were between 58% higher/37% lower (most reliable parameter; coefficient of variation of RR intervals) and 443% higher/82% lower (least reliable parameter; very low frequency power) than the first measure. The intraclass correlation coefficient ranged from 0.58 to 0.90 and sample size requirements from 20 to 93 patients per group. Agreement of categories of heart rate variability ranged from 79 to 96%. CONCLUSIONS: Short-term clinical measurements of heart rate variability in patients with Type 2 diabetes are characterized by poor absolute reliability, but substantial to good relative reliability, suggesting greater clinical utility in diagnosis than in sequential follow-up.

Arterial stiffness, central blood pressure and body size in health and disease.

BACKGROUND: Body size is associated with increased brachial systolic blood pressure (SBP) and aortic stiffness. The aims of this study were to determine the relationships between central SBP and body size (determined by body mass index (BMI), waist circumference and waist/hip ratio) in health and disease. We also sought to determine if aortic stiffness was correlated with body size, independent of BP. METHODS: BMI, brachial BP and estimated central SBP (by SphygmoCor and radial P2) were recorded in controls (n=228), patients with diabetes (n=211), coronary artery disease (n=184) and end-stage kidney disease (n=68). Additional measures of waist circumference and arterial stiffness (aortic and brachial pulse wave velocity (PWV)) were recorded in a subgroup of 75 controls (aged 51 ± 12 years) who were carefully screened for factors affecting vascular function. RESULTS: BMI was associated with brachial (r=0.30; P<0.001) and central SBP (r=0.29; P<0.001) in the 228 controls, but not the patient populations (r<0.13; P>0.15 for all comparisons). In the control subgroup, waist circumference was also significantly correlated with brachial SBP (r=0.29; P=0.01), but not central SBP (r=0.22; P=0.07). Independent predictors of aortic PWV in the control subgroup were brachial SBP (ß=0.43; P<0.001), age (ß=0.37; P<0.001), waist circumference (ß=0.39; P=0.02) and female sex (ß=-0.24; P=0.03), but not BMI. CONCLUSION: In health, there are parallel increases in central and brachial SBP as BMI increases, but these relationships are not observed in the presence of chronic disease. Moreover, BP is a stronger correlate of arterial stiffness than body size.

The endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) predicts LV mass independent of afterload.

BACKGROUND: Nitric oxide (NO) is a modulator of left ventricular hypertrophy (LVH) and myocardial relaxation. The impact of NO availability on development of LVH has never been demonstrated in humans. We tested the hypotheses that elevation of asymmetric dimethylarginine (ADMA) concentrations (biochemical marker of decreased NO generation), and impairment of vascular responsiveness to NO donor GTN, would each predict the presence of LVH and associated LV diastolic dysfunction in a normal aging population. METHODS AND RESULTS: In 74 subjects aged 68±6 years, LV volumes and mass indexed to height(2.7) (LVMI) were calculated from cardiac MRI. Despite the absence of clinically-defined LVH, there was a relationship (r=0.29; p=0.01) between systolic BP and LVMI. Both elevation of ADMA levels to the highest quartile or impairment of GTN responsiveness (determined by applanation tonometry) to the lowest quartile were determinants of LVMI independent of systolic BP (p=0.01 and p=0.03, respectively). Filling pressure (E/E' ratio from echocardiography) was increased in patients with impaired vascular NO responsiveness (p<0.05) irrespective of LVMI. ADMA remained a significant determinant of LVMI on multivariate analysis. CONCLUSIONS: These data imply that NO bioavailability within the myocardium modulates earliest stages of LVH development and facilitates development of diastolic dysfunction at a given LV mass.

A comparison of methods for assessing total arterial compliance.

There are several methods of assessing total arterial compliance (TAC) based on the two element Windkessel model, which is a ratio of pressure and volume, but the optimal technique is unclear. In this study, three methods of estimating TAC were compared to determine which was the most robust in a large group of patients with and without cardiovascular risk. In all, 320 patients (170 men; age 55+/-10) were studied; TAC was determined by the pulse-pressure method (PPM), the area method (AM) and the stroke volume/pulse-pressure method (SVPP). We obtained arterial waveforms using radial applanation tonometry, dimensions using two-dimensional echocardiography and flow data by Doppler. Clinical data, risk factors, echo parameters and TAC by all three methods were then compared. TAC (ml mm Hg(-1)) by the PPM was 1.24+/-0.51, by the AM 1.84+/-0.90 and by the SVPP 1.96+/-0.76 (P<0.0001 between groups). Correlation was good between all methods: PPM/AM r=0.83, PPM/SVPP r=0.94 and AM/SVPP r=0.80 (all P<0.0001). Subgroup analysis showed significant differences between patients with and those without cardiovascular risk for all three methods; TAC-AM and TAC-SVPP values were similar and significantly higher than TAC-PPM. The only significant relationships observed with TAC and echo parameters were in left ventricular (LV) septal thickness (R(2)=0.07; P<0.0001) and LV mass (R(2)=0.04; P=0.004). Normal and abnormal values of TAC vary according to method, which should be expressed. Each of the techniques shows good correlation with each other, however, values for TAC-PPM are significantly lower. TAC-PPM and TAC-SVPP are comparable in determining differences between groups with and without cardiovascular risk.

Improvement of left ventricular function by lifestyle intervention in obesity: contributions of weight loss and reduced insulin resistance.

AIMS/HYPOTHESIS: Weight excess and insulin resistance mediate the link between obesity and left ventricular dysfunction. We investigated the effect and mechanisms of lifestyle modification on left ventricular function changes in obese patients. METHODS: Reduction of body weight and insulin resistance was sought using a behavioural intervention programme including dietary restrictions and exercise training in 261 patients (age 45 +/- 13 years) with BMI >or=30 kg/m(2), no history of cardiac disease and a normal stress echocardiogram. Each patient underwent echocardiographic measurement of myocardial deformation and velocity at baseline and at 6 month follow-up. RESULTS: Improvements in left ventricular systolic and diastolic function were demonstrated only in patients with significant reduction of weight and/or insulin resistance. Left ventricular improvement was less frequent in patients with diabetes than in those without (52% vs 82% for strain, 50% vs 81% for strain rate and 59% vs 80% for peak early diastolic myocardial velocity). The independent predictors of improved left ventricular systolic function (increase in strain) were: weight reduction (beta = 0.14, p < 0.05), decrease in the HOMA insulin resistance index (beta = 0.20, p < 0.005) and absence of diabetes (beta = 0.18, p < 0.02). A decrease in HbA(1c) also predicted improvement of left ventricular diastolic function (beta = 0.26, p < 0.001). There was a parallel increment in exercise capacity with intervention and increase in strain was independently correlated with increase in VO(2) (beta = 0.13, p < 0.04). CONCLUSIONS/INTERPRETATION: Effective lifestyle modifications in obese patients improve left ventricular systolic and diastolic function, but appear less effective with co-existing diabetes. The reversal of left ventricular function abnormalities is associated with reduction of both weight and insulin resistance, and is accompanied by an increase in cardiorespiratory fitness.

The diabetic, hypertensive heart: epidemiology and mechanisms of a very high-risk situation.

The prevalence of diabetes is escalating, and is leading to increased rates of heart failure, myocardial infarction and cardiovascular death. Due to several inter-related biological processes, hypertension is often associated with diabetes, and accelerates these morbid conditions. These points are outlined below.

Effects of exercise intervention on myocardial function in type 2 diabetes.

OBJECTIVE: To identify the effects of a 1-year exercise intervention on myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM). DESIGN: Randomised controlled trial, the Diabetes Lifestyle Intervention Study. SETTING: University hospital. PATIENTS: 223 T2DM patients without occult coronary artery disease, aged 18-75 were randomised to an exercise training group (n = 111) or a usual care group (n = 112). Complete follow-up data were available in 176 (88 exercise, 88 usual care). INTERVENTIONS: Exercise training consisted of gym, followed by telephone-monitored home-based exercise training. MAIN OUTCOME MEASURES: Tissue Doppler-derived myocardial velocities, strain-rate and strain, body composition, glycated haemoglobin (HbA(1c)), maximum oxygen consumption (VO(2max)) and physical activity. RESULTS: Overall changes in myocardial function were not different between groups despite improvements in waist circumference, fat mass, blood glucose, HbA(1c), insulin sensitivity, VO(2max) and 6-minute walk distance in the intervention group (p<0.05). The latter also spent significantly more time in vigorous activity (p<0.05). A post-hoc analysis revealed that intervention patients who spent more time in both moderate and vigorous activity showed a significant improvement in myocardial tissue velocity (p<0.01), HbA(1c) (p = 0.03) and VO(2max) (p = 0.03) compared to controls. Myocardial strain rate (p = 0.03) and HbA(1c) improved in intervention patients with the greatest increase in moderate activity (p = 0.03). CONCLUSIONS: In patients with T2DM, current exercise recommendations led to an improvement in metabolic function, but failed to improve myocardial function in the overall group. Patients with greater increases in both moderate and vigorous activity showed improvements in myocardial function, glycaemic control and cardiorespiratory fitness. TRIAL REGISTRATION NUMBER: ACTRN12607000060448.

Strain rate evaluation of phasic atrial function in hypertension.

BACKGROUND: Strain (SI) and strain rate (SR) measure regional myocardial deformation and may be a new technique to assess phasic atrial function. OBJECTIVE: To examine the feasibility of using SI and SR to evaluate phasic atrial function in patients with mild hypertension (HT). PATIENTS AND METHODS: The study group comprised 54 patients with mild essential HT (29 women) and 80 age-matched normal controls (47 women). Standard two-dimensional and Doppler echocardiography was performed as well as Doppler tissue imaging. The following left atrial (LA) volumes were measured: (a) maximal LA volume or Vol(max); (b) minimal LA volume or Vol(min); (c) just before the "p" wave on ECG (Vol(p)). Phasic LA volumes were also calculated. Systolic (S-Sr), early diastolic (E-Sr), late diastolic (A-Sr) strain rate and SI were measured. RESULTS: Despite no differences in indexed maximal LA volume with only mild increases in left ventricular mass in the HT cohort compared with normal subjects (mean (SD) 86 (18) g/m(2) vs 67 (14) g/m(2); p = 0.001), E-Sr was significantly lower in the HT cohort. There was a corresponding reduction in indexed conduit volume in the HT cohort compared with normal subjects (10.5 (7.5) ml/m(2) vs 13.8 (6.1) ml/m(2); p = 0.006). Global E-Sr showed modest negative correlations with LA Vol(max) and LA ejection fraction. No significant difference was present in S-Sr, A-Sr or global atrial strain between the normal and HT cohorts. CONCLUSION: Mild HT results in a reduction in LA conduit volume, although maximal LA volume is unchanged. This is reflected by a reduction in E-Sr with preserved S-Sr and A-Sr.

Evolution and outcome of diastolic dysfunction.

BACKGROUND: Diastolic dysfunction (DD) is highly prevalent and associated with increased morbidity and mortality, but its natural history remains poorly defined. OBJECTIVE: This cohort study sought to characterise the influence of clinical features, medical therapy and echocardiographic parameters on the progression of DD. METHODS: We identified 926 consecutive patients (aged 62 (14) years, 221 women) with DD and preserved systolic function. A repeat echocardiogram was performed in 199 patients > or =1 year after the baseline study (average 3.6 (1.4) years). Follow-up for 4.8 (2.5) years was 97% complete for the major endpoint of all-cause mortality. Cox regression analyses were performed to identify the associations of mortality. RESULTS: Over follow-up, 142 patients died and 22 were admitted with heart failure. The independent predictors of death were age, hyperlipidaemia, co-morbid disease and restrictive filling. The degree of diastolic dysfunction remained stable in 52%, deteriorated in 27% and improved in 21%. There was a greater use of medical therapy in those with stable or worsening diastolic function; when the protective effects of these agents were taken into account in a multivariate model, improvement in diastolic dysfunction was associated with a survival benefit. CONCLUSION: DD is associated with all-cause mortality, independent of the presence of a major co-morbidity. The degree of DD remains stable in about 50% of patients, the population whose diastolic function improves over time has a more favourable outcome.

Diabetic heart disease.

Diabetes mellitus is responsible for a spectrum of cardiovascular disease. The best known complications arise from endothelial dysfunction, oxidation, inflammation, and vascular remodelling and contribute to atherogenesis. However, the effects on the heart also relate to concurrent hypertensive heart disease, as well as direct effects of diabetes on the myocardium. Diabetic heart disease, defined as myocardial disease in patients with diabetes that cannot be ascribed to hypertension, coronary artery disease, or other known cardiac disease, is reviewed.

Feasibility and clinical decision-making with 3D echocardiography in routine practice.

OBJECTIVE: To assess the feasibility and potential impact of routine three-dimensional (3D) echocardiographic assessment of left ventricular (LV) ejection fraction and volumes on clinical decision-making. METHODS: Patients referred to three hospital-based echocardiography laboratories underwent 2D echocardiography (2DE) and 3D echocardiography (3DE). Feasibility was assessed in a group of 168 unselected patients and decision-making assessed within an expanded group of 220 patients. The time for acquisition and measurement was obtained. Feasibility was defined by ability to measure LV parameters. The potential of 3DE to alter clinical decisions based on 2DE was evaluated by the ability to identify four clinically relevant measurement thresholds: (1) LV end-systolic volume (LVESV) >50 ml/m(2) (indication for surgery in regurgitant valve disease); (2) LVESV >30 ml/m(2) (prognosis after infarction); (3) LV ejection fraction (LVEF) <35% (indication for implantable defibrillator); and (4) LVEF <40% (indication for heart failure treatment). RESULTS: 3DE was technically feasible in 83% of unselected patients. The additional time for 3D acquisition and measurement was available in 184 patients and was 5.4 (SD 2.0) minutes. The use of 3DE changed categorisation in between 6-11% of patients. Within threshold categories, 3D reallocated 17.5% (11/63) of patients with LVEF <35%, 16.1% (13/81) for LVEF <40%, 12.4% (13/105) for LVESV >30 ml/m(2) and 8.5% (5/59) for LVESV >50 ml/m(2). Most of the impact of 3D was within 10 ml/m(2) of selected volume thresholds (>or=75%) and 10% of EF thresholds (>80%). CONCLUSION: Measurement of LV volumes and EF by 3DE is clinically feasible and has the potential to significantly alter clinical decision-making.