Survey of echocardiography practice across five continents.

BACKGROUND AND AIM: The term echocardiography refers to a diverse range of cardiovascular ultrasound imaging methods, both inside and outside specialist cardiology practice. While guidelines exist, we hypothesized that there are significant worldwide differences in the way echocardiography is practiced. We surveyed echocardiography practitioners around the world to characterize the workforce and their practice. METHOD: Social media and word of mouth were used in an explosive sampling approach to recruit echo users, who then completed an online survey that included personal demographics and questions about their practice, their resources, and daily use of echocardiography. RESULTS: In total, 594 participants completed the survey: 54.9% sonographers; 30% cardiologists, with the remainder other physicians or trainees. Significant variation in the number of echoes performed and the time allocated to scanning was observed. There were also differences in the gathering of adjunct measures such as blood pressure and body size. CONCLUSION: There is wide variation in echocardiography practices across the world. Differences are likely to be both clinician- and healthcare system-driven. Guidelines for practice developed in well-resourced western countries and intended for use in cardiology-based echocardiography laboratories may not be applicable to other countries or indeed to new echo users.

Adjunct Methods for the Detection of Patent Foramen Ovale: The Contribution of Transcranial Doppler and the Valsalva Manoeuvre.

A patent foramen ovale (PFO) is present in 25% of the population. In some patients, especially those without traditional stroke risk factors and with no immediately apparent cause, a cryptogenic stroke may be caused by an embolus passing through the PFO to the systemic circulation. The identification, or indeed exclusion, of a PFO is sought in these patients, most commonly using contrast-enhanced transthoracic or transoesophageal echocardiography. Another method for detecting a PFO is transcranial Doppler, which allows the detection of PFO possibly without the need for an echo laboratory, and with arguably improved sensitivity. This review will focus on transcranial Doppler detection of PFO, with a brief summary of echocardiographic techniques and the use of ultrasound contrast agents, and the role of provocations to increase diagnostic accuracy, specifically the Valsalva manoeuvre. We discuss the phases alongside the direct and indirect signs of an adequate Valsalva manoeuvre.

Estimating heart mass from heart volume as measured from post-mortem computed tomography.

Heart mass can be predicted from heart volume as measured from post-mortem computed tomography (PMCT), but with limited accuracy. Although related to heart mass, age, sex, and body dimensions have not been included in previous studies using heart volume to estimate heart mass. This study aimed to determine whether heart mass estimation can be improved when age, sex, and body dimensions are used as well as heart volume. Eighty-seven (24 female) adult post-mortem cases were investigated. Univariable predictors of heart mass were determined by Spearman correlation and simple linear regression. Stepwise linear regression was used to generate heart mass prediction equations. Heart mass estimate performance was tested using median mass comparison, linear regression, and Bland-Altman plots. Median heart mass (P = 0.0008) and heart volume (P = 0.008) were significantly greater in male relative to female cases. Alongside female sex and body surface area (BSA), heart mass was univariably associated with heart volume in all cases (R2 = 0.72) and in male (R2 = 0.70) and female cases (R2 = 0.64) when segregated. In multivariable regression, heart mass was independently associated with age and BSA (R2 adjusted = 0.46-0.54). Addition of heart volume improved multivariable heart mass prediction in the total cohort (R2 adjusted = 0.78), and in male (R2 adjusted = 0.74) and female (R2 adjusted = 0.74) cases. Heart mass estimated from multivariable models incorporating heart volume, age, sex, and BSA was more predictive of actual heart mass (R2 = 0.75-0.79) than models incorporating either age, sex, and BSA only (R2 = 0.48-0.57) or heart volume only (R2 = 0.64-0.73). Heart mass can be more accurately predicted from heart volume measured from PMCT when combined with the classical predictors, age, sex, and BSA.

Sex Disparity in Cardiovascular Disease Outcomes: Do Our Current Echocardiographic Reference Ranges Measure Up?

Reducing inequity in access to health care and disparity in health outcomes remain key objectives in cardiovascular medicine. Echocardiography is often the primary diagnostic tool used to detect cardiovascular disease (CVD), and relies on comparison with published reference ranges to appropriately detect pathology. Our understanding of the contribution of age, sex and ethnicity to quantification of cardiac size is improving, but cardiovascular disease management guidelines have yet to evolve. While recently, sex, age and ethnicity-specific reference values have been produced, treatment thresholds in many clinical guidelines do not differentiate between sexes. As a result, in order to reach management thresholds, women are often required to have more severe pathology. In order to reduce potential disadvantage to women, future research efforts should be directed to develop more personalised treatment approaches by identification of sex-appropriate management thresholds.

The 21st Century Echocardiography Laboratory in Australia and New Zealand: Rapid Evolution of Training and Workforce, Practice and Technology.

Echocardiography is a common and increasingly used noninvasive imaging tool in medicine. In this paper, we imagine the echocardiography laboratory of the future and consider the challenges we face currently, and may face in the future, and how these might be overcome; challenges such as training enough sonographers to meet the increasing demands of the ageing population living with chronic cardiovascular disease and the need for surveillance in other clinical scenarios. We consider the changing qualification framework and the requirements for accreditation and registration in Australia and New Zealand and the potential for migrant sonographers to meet some of the increasing demand. Advanced scopes of practice are likely to be a feature of the future workforce and we consider some of the ways these may evolve. Lastly, we consider how the evolving clinical landscape and technology may change the way echocardiography is delivered.

Plasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF system SNPs as prognostic biomarkers in patients with acute coronary syndromes.

BACKGROUND: Development of collateral circulation in coronary artery disease is cardio-protective. A key process in forming new blood vessels is attraction to occluded arteries of monocytes with their subsequent activation as macrophages. In patients from a prospectively recruited post-acute coronary syndromes cohort we investigated the prognostic performance of three products of activated macrophages, soluble vascular endothelial growth factor (VEGF) receptors (sFlt-1 and sKDR) and pterins, alongside genetic variants in VEGF receptor genes, VEGFR-1 and VEGFR-2. METHODS: Baseline levels of sFlt-1 (VEGFR1), sKDR (VEGFR2) and pterins were measured in plasma samples from subgroups (n = 513; 211; 144, respectively) of the Coronary Disease Cohort Study (CDCS, n = 2067). DNA samples from the cohort were genotyped for polymorphisms from the VEGFR-1 gene SNPs (rs748252 n = 2027, rs9513070 n = 2048) and VEGFR-2 gene SNPs (rs2071559 n = 2050, rs2305948 n = 2066, rs1870377 n = 2042). RESULTS: At baseline, levels of sFlt-1 were significantly correlated with age, alcohol consumption, NTproBNP, BNP and other covariates relevant to cardiovascular pathophysiology. Total neopterin levels were associated with alcohol consumption at baseline. 7,8 dihydroneopterin was associated with BMI. The A allele of VEGFR-2 variant rs1870377 was associated with higher plasma sFlt-1 and lower levels of sKDR at baseline. Baseline plasma sFlt-1 was univariately associated with all cause mortality with (p < 0.001) and in a Cox's proportional hazards regression model sFlt-1 and pterins were both associated with mortality independent of established predictors (p < 0.027). CONCLUSIONS: sFlt-1 and pterins may have potential as prognostic biomarkers in acute coronary syndromes patients. Genetic markers from VEGF system genes warrant further investigation as markers of levels of VEGF system components in these patients. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry. ACTRN12605000431628 . 16 September 2005, Retrospectively registered.

C-Type Natriuretic Peptides in Coronary Disease.

AIMS: C-type natriuretic peptide (CNP) is a paracrine growth factor expressed in the vascular endothelium. Although upregulated in atheromatous arteries, the predictive value of plasma CNP products for outcome in coronary disease is unknown. This study aimed to compare the prognostic value of plasma CNP products with those of other natriuretic peptides in individuals with coronary artery disease, and investigate their associations with cardiac and renal function. METHODS AND RESULTS: Plasma concentrations of CNP and amino-terminal proCNP (NT-proCNP) were measured at baseline in 2129 individuals after an index acute coronary syndrome admission and related to cardiac and renal function, other natriuretic peptides [atrial NP (ANP) and B-type NP (BNP)] and prognosis (primary end point, mortality; secondary end point, cardiac readmission). Median follow-up was 4 years. At baseline, and in contrast to CNP, ANP, and BNP, plasma NT-proCNP was higher in males and weakly related to cardiac function but strongly correlated to plasma creatinine. All NPs were univariately associated with mortality. Resampling at 4 and 12 months in survivors showed stable concentrations of NT-proCNP whereas all other peptides declined. When studied by diagnosis (myocardial infarction, unstable angina) at index admission using a multivariate model, NT-proBNP predicted mortality and readmission in myocardial infarction. In unstable angina, only NT-proCNP predicted both mortality and cardiac readmission. CONCLUSIONS: In contrast to the close association of NT-proBNP with cardiac function, and predictive value for outcome after myocardial infarction, plasma NT-proCNP is highly correlated with renal function and is an independent predictor of mortality and cardiac readmission in individuals with unstable angina.

The Validity of Left Ventricular Mass as a Surrogate End Point for All-Cause and Cardiovascular Mortality Outcomes in People With CKD: A Systematic Review and Meta-analysis.

BACKGROUND: Left ventricular mass (LVM) is a widely used surrogate end point in randomized trials involving people with chronic kidney disease (CKD) because treatment-induced LVM reductions are assumed to lower cardiovascular risk. The aim of this study was to assess the validity of LVM as a surrogate end point for all-cause and cardiovascular mortality in CKD. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Participants with any stages of CKD. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials with 3 or more months' follow-up that reported LVM data. INTERVENTION: Any pharmacologic or nonpharmacologic intervention. OUTCOMES: The surrogate outcome of interest was LVM change from baseline to last measurement, and clinical outcomes of interest were all-cause and cardiovascular mortality. Standardized mean differences (SMDs) of LVM change and relative risk for mortality were estimated using pairwise random-effects meta-analysis. Correlations between surrogate and clinical outcomes were summarized across all interventions combined using bivariate random-effects Bayesian models, and 95% credible intervals were computed. RESULTS: 73 trials (6,732 participants) covering 25 intervention classes were included in the meta-analysis. Overall, risk of bias was uncertain or high. Only 3 interventions reduced LVM: erythropoiesis-stimulating agents (9 trials; SMD, -0.13; 95% CI, -0.23 to -0.03), renin-angiotensin-aldosterone system inhibitors (13 trials; SMD, -0.28; 95% CI, -0.45 to -0.12), and isosorbide mononitrate (2 trials; SMD, -0.43; 95% CI, -0.72 to -0.14). All interventions had uncertain effects on all-cause and cardiovascular mortality. There were weak and imprecise associations between the effects of interventions on LVM change and all-cause (32 trials; 5,044 participants; correlation coefficient, 0.28; 95% credible interval, -0.13 to 0.59) and cardiovascular mortality (13 trials; 2,327 participants; correlation coefficient, 0.30; 95% credible interval, -0.54 to 0.76). LIMITATIONS: Limited long-term data, suboptimal quality of included studies. CONCLUSIONS: There was no clear and consistent association between intervention-induced LVM change and mortality. Evidence for LVM as a valid surrogate end point in CKD is currently lacking.

Effects of a healthier snack on snacking habits and glycated Hb (HbA1c): a 6-week intervention study.

Dietary behaviour modification may change eating habits and reduce the impact of poor nutrition. This study aimed to evaluate the effects of daily consumption of a healthier snack bar on snacking habits and glycated Hb (HbA1c) within a 6-week intervention. In all, twenty-eight participants were randomly allocated to two groups to either consume the bars as the main snack for 6 weeks (n 14) or receipt of the bars was delayed for 6 weeks (n 14) following a stepped-wedge design. All participants had HbA1c concentrations measured at weeks -1, 0, 4, 6, 10 and 12. A short dietary habits questionnaire was self-completed at weeks 0, 6 and 12. Participants consumed the bars they received instead of other snacks, and found that the healthier snack bar was acceptable as part of their daily dietary pattern. Over the 12 weeks, there was a significant reduction in intake of biscuits, cakes and pies (approximately 2 servings/week, P<0·05) in both groups. Fruit juice intake was reduced (approximately 1 serving/week, P=0·029) in the first group. In all, twenty participants (71·4 %) experienced a decrease (n 15) or no change (n 5) in HbA1c (range 0-4 mmol/mol), whereas eight participants experienced an increase in HbA1c (range 0·5-2·5 mmol/mol). There was high compliance with the healthier snack intervention and a trend towards a favourable effect on glucose homoeostasis. Habitual snacking behaviour has the potential to be improved through changes in the food supply, and in the longer term may reduce the impact of poor nutrition on public health.

Arterial baroreceptor reflex control of renal sympathetic nerve activity following chronic myocardial infarction in male, female, and ovariectomized female rats.

There is controversy regarding whether the arterial baroreflex control of renal sympathetic nerve activity (SNA) in heart failure is altered. We investigated the impact of sex and ovarian hormones on changes in the arterial baroreflex control of renal SNA following a chronic myocardial infarction (MI). Renal SNA and arterial pressure were recorded in chloralose-urethane anesthetized male, female, and ovariectomized female (OVX) Wistar rats 6-7 wk postsham or MI surgery. Animals were grouped according to MI size (sham, small and large MI). Ovary-intact females had a lower mortality rate post-MI (24%) compared with both males (38%) and OVX (50%) (P < 0.05). Males and OVX with large MI, but not small MI, displayed an impaired ability of the arterial baroreflex to inhibit renal SNA. As a result, the male large MI group (49 ± 6 vs. 84 ± 5% in male sham group) and OVX large MI group (37 ± 3 vs. 75 ± 5% in OVX sham group) displayed significantly reduced arterial baroreflex range of control of normalized renal SNA (P < 0.05). In ovary-intact females, arterial baroreflex control of normalized renal SNA was unchanged regardless of MI size. In males and OVX there was a significant, positive correlation between left ventricle (LV) ejection fraction and arterial baroreflex range of control of normalized renal SNA, but not absolute renal SNA, that was not evident in ovary-intact females. The current findings demonstrate that the arterial baroreflex control of renal SNA post-MI is preserved in ovary-intact females, and the state of left ventricular dysfunction significantly impacts on the changes in the arterial baroreflex post-MI.

Heart failure in younger patients: the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC).

AIM: Our understanding of heart failure in younger patients is limited. The Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) database, which consisted of 24 prospective observational studies and 7 randomized trials, was used to investigate the clinical characteristics, treatment, and outcomes of younger patients. METHODS AND RESULTS: Patients were stratified into six age categories: <40 (n = 876), 40-49 (n = 2638), 50-59 (n = 6894), 60-69 (n = 12 071), 70-79 (n = 13 368), and ≥80 years (n = 6079). Of 41 926 patients, 2.1, 8.4, and 24.8% were younger than 40, 50, and 60 years of age, respectively. Comparing young (<40 years) against elderly (≥80 years), younger patients were more likely to be male (71 vs. 48%) and have idiopathic cardiomyopathy (63 vs. 7%). Younger patients reported better New York Heart Association functional class despite more severe left ventricular dysfunction (median ejection fraction: 31 vs. 42%, all P < 0.0001). Comorbidities such as hypertension, myocardial infarction, and atrial fibrillation were much less common in the young. Younger patients received more disease-modifying pharmacological therapy than their older counterparts. Across the younger age groups (<40, 40-49, and 50-59 years), mortality rates were low: 1 year 6.7, 6.6, and 7.5%, respectively; 2 year 11.7, 11.5, 13.0%; and 3 years 16.5, 16.2, 18.2%. Furthermore, 1-, 2-, and 3-year mortality rates increased sharply beyond 60 years and were greatest in the elderly (≥80 years): 28.2, 44.5, and 57.2%, respectively. CONCLUSION: Younger patients with heart failure have different clinical characteristics including different aetiologies, more severe left ventricular dysfunction, and less severe symptoms. Three-year mortality rates are lower for all age groups under 60 years compared with older patients.

Predicting survival in heart failure: a risk score based on 39 372 patients from 30 studies.

AIMS: Using a large international database from multiple cohort studies, the aim is to create a generalizable easily used risk score for mortality in patients with heart failure (HF). METHODS AND RESULTS: The MAGGIC meta-analysis includes individual data on 39 372 patients with HF, both reduced and preserved left-ventricular ejection fraction (EF), from 30 cohort studies, six of which were clinical trials. 40.2% of patients died during a median follow-up of 2.5 years. Using multivariable piecewise Poisson regression methods with stepwise variable selection, a final model included 13 highly significant independent predictors of mortality in the following order of predictive strength: age, lower EF, NYHA class, serum creatinine, diabetes, not prescribed beta-blocker, lower systolic BP, lower body mass, time since diagnosis, current smoker, chronic obstructive pulmonary disease, male gender, and not prescribed ACE-inhibitor or angiotensin-receptor blockers. In preserved EF, age was more predictive and systolic BP was less predictive of mortality than in reduced EF. Conversion into an easy-to-use integer risk score identified a very marked gradient in risk, with 3-year mortality rates of 10 and 70% in the bottom quintile and top decile of risk, respectively. CONCLUSION: In patients with HF of both reduced and preserved EF, the influences of readily available predictors of mortality can be quantified in an integer score accessible by an easy-to-use website www.heartfailurerisk.org. The score has the potential for widespread implementation in a clinical setting.

The impact of beta-blockade on right ventricular function in mitral regurgitation.

BACKGROUND: Although mitral regurgitation (MR) results in left ventricular (LV) volume overload, right ventricular (RV) function may also be impaired. We investigated the influence of short-term beta-blockade on RV function in patients with moderate-severe MR. METHODS: Twenty-six patients were randomised in a cross-over design to receive two weeks of beta-blockade or placebo. Echocardiography was performed at baseline and at the end of the treatment periods. Measurements included: RV ejection fraction (RVEF) tricuspid annular motion and Tei index. RESULTS: No differences in mean RVEF (64.0 ± 6.0 v 67.0 ± 8.0%, p=0.3), tricuspid annular motion (13.5 ± 3.0 v 14.7 ± 2.9 cm/s, p=0.5), or median Tei index (0.61 (0.54, 0.88) v 0.59 (0.54, 0.74), p=0.8) were observed between placebo and metoprolol, despite significantly longer cardiac time intervals. Tei index under both conditions was significantly reduced. CONCLUSIONS: Short-term treatment with a beta-blocker did not influence RV function in these patients. Interestingly, the RV Tei index was high suggesting significant RV dysfunction despite normal RVEF.

Effect of early initiation of dialysis on cardiac structure and function: results from the echo substudy of the IDEAL trial.

BACKGROUND: Abnormalities of cardiac structure and function are common in patients undergoing dialysis, and cardiovascular disease is the major cause of mortality in this group. Heart failure is a common clinical manifestation of cardiovascular disease and is preceded by left ventricular hypertrophy (LVH). There are variable reports about the impact of dialysis on LVH, both deleterious and beneficial. Our study investigated whether the timing of the initiation of dialysis therapy had an impact on cardiac structure and function. STUDY DESIGN: Randomized controlled trial. SETTING & PARTICIPANTS: This is a cardiac substudy involving 182 patients with stage 5 chronic kidney disease in the IDEAL (Initiating Dialysis Early and Late) trial. INTERVENTION: The IDEAL trial randomly assigned patients on the basis of estimated glomerular filtration rate (eGFR), calculated using the Cockcroft-Gault equation, to start dialysis therapy early (GFR, 10-14 mL/min/1.73 m(2)), with the others starting late (GFR, 5-7 mL/min/1.73 m(2)). OUTCOMES & MEASUREMENTS: Echocardiograms were obtained at baseline and 12 months after randomization. Primary outcomes were change in left ventricular mass indexed for height (LVMi) between baseline and 12 months, left ventricular ejection fraction, left ventricular systolic annular velocity, ratio of mitral inflow velocity (E) to mitral annular velocity (Ea) (E/Ea), and left atrial volume indexed for height (LAVi). RESULTS: LVMi at baseline was elevated, but similar in both groups, with no significant change within or between groups at 12 months. E/Ea and LAVi were increased at baseline, consistent with significant diastolic dysfunction; there were no differences between groups at 12 months and no changes were observed for left ventricular volumes, left ventricular ejection fraction, stroke volume, and other echocardiographic parameters. LIMITATIONS: Small multicenter study using echocardiography. CONCLUSIONS: Advanced cardiac disease in these patients with stage 5 chronic kidney disease did not progress during the 12-month study period and planned early initiation of dialysis therapy did not result in differences in any echocardiographic variables of cardiac structure and function.

Abbreviated Echocardiographic Screening for Rheumatic Heart Disease by Nonexperts with and without Offsite Expert Review: A Diagnostic Accuracy Study.

BACKGROUND: Early detection of rheumatic heart disease (RHD) through echocardiographic screening can facilitate early access to effective treatment, which reduces the risk for progression. Accurate, feasible approaches to echocardiographic screening that can be incorporated into routine health services are needed. The authors hypothesized that offsite expert review could improve the diagnostic accuracy of nonexpert-obtained echocardiographic images. METHODS: This prospective cross-sectional study was performed to evaluate the diagnostic accuracy of health worker-conducted single parasternal long-axis view with a sweep of the heart using hand-carried ultrasound for the detection of RHD in high-risk populations in Timor-Leste and Australia. In the primary analysis, the presence of any mitral or aortic regurgitation met the criteria for a positive screening result. Sensitivity and specificity were calculated for a screen-and-refer approach based on nonexpert practitioner assessment (approach 1) and for an approach using offsite expert review of nonexpert practitioner-obtained images to decide onward referral (approach 2). Each participant had a reference test performed by an expert echocardiographer on the same day as the index test. Diagnosis of RHD was determined by a panel of three experts, using 2012 World Heart Federation criteria. RESULTS: The prevalence of borderline or definite RHD among 3,329 participants was 4.0% (95% CI, 3.4%-4.7%). The sensitivity of approach 1 for borderline or definite RHD was 86.5% (95% CI, 79.5%-91.8%), and the specificity was 61.4% (95% CI, 59.7%-63.1%). Approach 2 achieved similar sensitivity (88.4%; 95% CI, 81.5%-93.3%) and improved specificity (77.1%; 95% CI, 75.6%-78.6%). CONCLUSION: Nonexpert practitioner-obtained single parasternal long-axis view with a sweep of the heart images, reviewed by an offsite expert, can detect borderline and definite RHD on screening with reasonable sensitivity and specificity. Brief training of nonexpert practitioners with ongoing support could be used as an effective strategy for scaling up echocardiographic screening for RHD in high-risk settings.

KCNE5 polymorphism rs697829 is associated with QT interval and survival in acute coronary syndromes patients.

INTRODUCTION: The KCNE family is a group of small transmembrane channel proteins involved in potassium ion (K(+)) conductance. The X-linked KCNE5 gene encodes a regulator of the K(+) current mediated by the potassium channel KCNQ1. Polymorphisms in KCNE5 have been associated with altered cardiac electrophysiological properties in human studies. We investigated associations of the common rs697829 polymorphism from KCNE5 with baseline characteristics, baseline electrocardiographic (ECG) measurements, and patient survival in a cohort of post-acute coronary syndromes (ACS) patients (the Coronary Disease Cohort Study cohort). METHODS AND RESULTS: DNA samples (n = 1,740) were genotyped for rs697829 using a TaqMan assay. Baseline ECG data revealed corrected QT (QTc) interval was associated with rs697829 in male, but not female, patients, being extended in the G genotype group (A 416 ± 1.71; G 431 ± 4.25 ms, P = 0.002). Covariate-adjusted survival was poorest in G genotype patients in Cox proportional hazard modeling of mortality data of males (P(overall) = 0.020). Male patients with G genotype had a hazard ratio of 1.44 (1.11-2.33) for death when compared to the A genotype male patients (P = 0.048) after adjustment for age, baseline log-transformed N-terminal pro-B-type natriuretic peptide (NTproBNP), ß-blocker and insulin treatment, QTc interval, history of myocardial infarction, and physical activity score. CONCLUSION: This study suggests an association between rs697829, a common single nucleotide polymorphism (SNP) from KCNE5, and ECG measurements and survival in postacute ACS patients. Prolonged subclinical QT interval may be a marker of adverse outcome in this group of patients.

New Echocardiography Reference Ranges for Aotearoa (NewERA) Study: the application of international echocardiographic reference values to linear measurements of the hearts of healthy, young Maori and Pacific adults may not detect cardiac enlargement.

AIMS: To develop ethnic-specific echocardiography reference ranges for Aotearoa, and to investigate the impact of indexation to body surface area (BSA). Current reference international ranges are derived from people of mostly NZ European ethnicity and may not be appropriate for Maori and New Zealanders of Pacific ethnicity, who both experience high rates of cardiovascular disease. METHODS: Echocardiography was performed in a cross-sectional study of 263 healthy adults (18-50 years): Maori (N=71, 43 female), Pacific (N=53, 28 female), European (N=139, 74 female). Linear measurements of the left heart are reported and indexed to BSA. The upper/lower limit of normal (ULN/LLN) by ethnicity and sex were derived (quantile regression). Ethnic- and sex-specific differences were examined using ANOVA. RESULTS: The ULN was higher for all un-indexed dimensions in men compared to women, and for most indices the ULN was smallest in NZ Europeans and largest in Maori and Pacific peoples. Indexation reversed these relationships: NZ Europeans had higher ULN for many measurements. CONCLUSIONS: Indexing to BSA introduced bias that preferences the NZ European ethnicity by creating an upper limit reference threshold that far exceeds this sample's upper range. As a result, this may lead to under-recognition of cardiac enlargement in Maori and Pacific patients, and in particular for women. Unique reference ranges for all ethnic groups and sexes are required to optimally detect and manage cardiovascular diseases (CVD) in Aotearoa.

Association of genetic variation in the natriuretic peptide system with cardiovascular outcomes.

Polymorphisms within individual natriuretic peptide genes have been associated with risk factors for cardiovascular disease, but their association with clinical outcomes was previously unknown. This study aimed to investigate the association between genetic variants in key genes of the natriuretic peptide system with cardiovascular outcomes in patients with coronary artery disease. Coronary disease patients (n=1810) were genotyped for polymorphisms within NPPA, NPPB, NPPC, NPR1 and NPR2. Clinical history, natriuretic peptide concentrations, echocardiography, all-cause mortality and cardiovascular hospital readmissions were recorded over a median 2.8 years. Minor alleles of NPPA rs5068, rs5065 and rs198358 were associated with less history of hypertension; minor alleles of NPPA rs5068 and rs198358 was also associated with higher circulating natriuretic peptide levels (p=0.003 to p=0.04). Minor alleles of NPPB rs198388, rs198389, and rs632793 were associated with higher circulating BNP and NT-proBNP (p=0.001 to p=0.03), and reduced E/E(1) (p=0.011), or LVESVI (p=0.001) and LVEDVI (p=0.004). Within NPPC, both rs11079028 and rs479651 were associated with higher NT-proBNP and CNP (p=0.01 to p=0.03), and rs479651 was associated with lower LVESVI (p=0.008) and LVEDVI (p=0.018). NPR2 rs10758325 was associated with smaller LVMI (p<0.02). A reduced rate of cardiovascular readmission was observed for minor alleles of NPPA rs5065 (p<0.0001), NPPB rs632793 (p<0.0001), rs198388 (p<0.0001), rs198389 (p<0.0001), and NPR2 rs10758325 (p<0.0001). There were no associations with all-cause mortality. In established cardiovascular disease, natriuretic peptide system polymorphisms were associated with natriuretic peptide levels, hypertension, echocardiographic indices and the incidence of hospital readmission for cardiovascular events.