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SUMMARY Scleroderma affects the left heart directly and indirectly via the effects of systemic hypertension. Using transthoracic echocardiography, we evaluated 35 patients with scleroderma and compared them with matched control subjects. Compared with controls, there were no differences between left ventricular dimensions, wall thickness, calculated mass or fractional shortening. However, the left atrium was enlarged (P = 0.006) and the mitral deceleration time was prolonged (P = 0.0005) in patients with scleroderma; suggesting abnormal diastolic function. After adjusting for potential confounders, duration of Raynaud's was found to be an independent predictor of deceleration time (P = 0.04), E/A peak velocity ratio (P = 0.04), A peak velocity (P = 0.004) and A velocity time integral (P = 0.0001), all measures of diastolic function. This group of individuals with scleroderma have evidence of abnormal diastolic function of the left ventricle despite normal left ventricular size and systolic function, and in the absence of hypertrophy. This finding is independent of the use of vasoactive medications and history of systemic hypertension, and thus may be due to primary myocardial involvement by scleroderma. The tendency to abnormal diastolic function of the left ventricle correlated with the duration of Raynaud's phenomenon.

Ischaemic heart disease is a major problem in the elderly. Compared with younger patients, coexisting medical conditions are more common and the patients are more likely to be receiving multiple drugs. In addition, drug pharmacodynamics are altered in the elderly and this needs to be carefully considered when commencing treatment for angina. In practice, the general principles of management of elderly patients with angina are similar to that of younger patients. However, particular care needs to be taken with the therapeutic regimens used. This article reviews the approach to the treatment of stable exertional angina in the elderly.

To the Editor: Nonspecific markers of inflammation such as C-reactive protein (CRP) are now recognized as major risk factors for cardiovascular events. General population studies have reported an inverse association between serum CRP levels and self-reported physical activity or physical fitness ([

Self-reported health and disease status is a common method used in epidemiologic studies and surveys involving younger populations, but its reliability in octogenarians is unknown. The objective of the present study was to examine the level of agreement between self-reports and medical records on specific cardiovascular diagnoses.The Life and Living to Advanced Age: a Cohort Study in New Zealand recruited 937 octogenarians in New Zealand. Standardized questionnaires were administered to determine sociodemographic status and medical history. Diagnoses of myocardial infarction (MI), stroke, congestive heart failure (CHF), and hypertension were compared between self-reports and two combined sources of medical records.There were moderate levels of agreement between self-reports and medical records for MI, stroke, and hypertension (κ = 0.43-0.45) and low levels for CHF (κ = 0.19). The proportion of discordance for MI, stroke, CHF, and hypertension was 16%, 12%, 22%, and 27%, respectively. Adjusting for socioeconomic-demographic status and cognitive function, the number of comorbidities is highly associated with agreement between self-reports and medical records (P 0.01). Gender, socioeconomic status, and cognitive function were also related to agreement between self-reports and medical records, but the strength of association was ethnic specific.Self-reported information on specific cardiovascular conditions has only modest reliability in octogenarians and is associated with number of comorbidities.

The progression of hypertensive heart disease (HHD) to heart failure (HF) is associated with myocardial remodeling. Corresponding changes in three-dimensional organization of cardiac extracellular matrix have not been quantified or related fully to the development of HF. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto controls were studied at 3, 12, 18, and 24 mo. Hemodynamic and morphological data, brain natriuretic peptide levels, and echocardiography demonstrate four distinct disease stages: systemic hypertension, diastolic dysfunction, early systolic failure, and decompensated HF. Passive left ventricular (LV) pressure-volume relationships were determined in vitro. Transmural specimens from the anterior LV free wall were imaged using extended-volume confocal microscopy, and three-dimensional myocardial architecture was quantified. In SHRs, LV compliance was reduced at 12 mo and increased progressively thereafter. However, it was less than in controls for filling pressures

Despite recent improvements in the management of congestive heart failure, the prognosis of many patients with this condition remains poor. The level of neurohormonal activation appears to be predictive of survival, and clinical studies indicate that inhibition of overactivated neurohormonal systems may be beneficial. Activation of the renin-angiotensin-aldosterone system is well documented in heart failure, and angiotensin-converting ensyme inhibition now has an established role in treatment based on evidence of hemodynamic, symptomatic and mortality benefit. Sympathetic nervous system activation also occurs as a compensatory mechanism in heart failure but with long-term deleterious effects, Increasing evidence suggests that beta-adrenergic blockade can produce hemodynamic and symptomatic improvement in heart failure of idiopathic or ischemic etiology. Trials of beta-adrenergic blocking agents in patients after myocardial infarction suggest a beneficial effect on mortality, even among those with heart failure. However, there remains uncertainty as to how generalizable are the results from the postinfarction trials, particularly in the current therapeutic environment with routine angiotensin-converting enzyme inhibitor therapy. Appropriately powered randomized, controlled trials are required to determine precisely the balance of benefit and risk resulting from long-term beta-blocker therapy in patients with heart failure of ischemic and other etiology.

To document levels of cardiovascular disease (CVD), diagnosed and undiagnosed risk factors and clinical management of CVD risk in rural Māori.Participants (aged 20-64 years), of Māori descent and self-report, were randomly sampled to be representative of age and gender profiles of the community. Screening clinics included health questionnaires, fasting blood samples, blood pressure and anthropometric measures. Data were obtained from participants' primary care physicians regarding prior diagnoses and current clinical management. New Zealand Cardiovascular Guidelines were used to identify new diagnoses at screening and Bestpractice electronic-decision support software used to estimate 5-year CVD risk.Mean age of participants (n=252) was 45.7 ± 0.7, 8% reported a history of cardiac disease, 43% were current smokers, 22% had a healthy BMI, 30% were overweight and 48% obese. Hypertension was previously diagnosed in 25%; an additional 22% were hypertensive at screening. Dyslipidaemia was previously diagnosed in 14% and an additional 43% were dyslipidaemic at screening. Type-2 diabetes was previously diagnosed in 11%. Glycaemic control was achieved in only 21% of those with type-2 diabetes. Blood pressure and cholesterol were above recommended targets in more than half of those with diagnosed CVD risk factors.High levels of diagnosed and undiagnosed CVD risk factors, especially hypertension, dyslipidaemia and diabetes were identified in this rural Māori community.There is a need for opportunistic screening and intensified management of CVD risk factors in this indigenous population group.

Chronic illness is the leading cause of morbidity, mortality, and inequitable health outcomes in New Zealand. The ABCCNZ Stocktake aimed to identify extent of long-term conditions management evidence-based practices in stroke, cardiovascular disease, chronic obstructive pulmonary disease and congestive heart failure in New Zealand's District Health Boards (DHBs).Eleven 'dimensions' of care for long-term conditions, identified by literature review and confirmed at workshops with long-term conditions professionals, formed the basis of the Stocktake of all 21 DHBs. It comprised two questionnaires: a generic component capturing perceptions of practice; and a disease-specific component assessing service provision.Fifteen DHBs completed all or parts of the questionnaires. Data accrual was completed in July 2008. Although most DHBs had developed long-term conditions management strategies to a moderate degree, there was considerable variability of practice between DHBs. DHBs thought their PHOs had developed strategies in some areas to a low to moderate level, though cardiovascular disease provision rated more highly. Regarding disease-specific services, larger DHBs had greater long-term conditions management provision not only of tertiary services, but of standard care, leadership, self-management, case-management, and audit.There is considerable variability in perceptions of long-term conditions management service provision across DHBs. In many instances variability in actual disease-specific service provision appears to relate to DHB size.

KCNE5 Gene Variant, QTc and Survival in ACS. Introduction: The KCNE family is a group of small transmembrane channel proteins involved in potassium ion (K + )c onductance. The X-linkedKCNE5 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 investigatedassociationsofthecommonrs697829polymorphismfromKCNE5withbaselinecharacteristics, baselineelectrocardiographic (ECG)measurements,andpatientsurvivalinacohortofpost-acutecoronary 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 (Poverall = 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), ! -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. (J Cardiovasc

Aim To determine whether the larger exercise stroke volume in senior endurance-trained athletes results from an attenuation of age-related alterations in left ventricular (LV) early diastolic filling or a more vigorous late filling. Methods Body composition (DEXA), VO2peak, stroke volume (CO2 rebreathing) and Doppler measures of early and late mitral inflow and mitral annular velocities were collected at seated upright rest and heart rate–matched exercise (100 and 120 bpm) in trained and untrained younger (18–30 years) men and trained and untrained older (60–80 years) healthy men. Results Ageing had a greater effect than training status on seated rest mitral inflow and tissue Doppler imaging parameters, as shown by a lower peak early-to-late mitral inflow velocity ratio (E/A ratio) and slower peak early mitral annular velocity (Em) in older compared with younger men. Exercise stroke volume was unaffected by healthy ageing; however, Em, an index of early LV lengthening rate and relaxation, was slower (P

To report the processes and protocols that were developed in the design and implementation of the Hauora Manawa Project, a cohort study of heart disease in New Zealand and to report the participation at baseline.This study utilised application of a Kaupapa Māori Methodology in gaining tribal and health community engagement, design of the project and random selection of participants from territorial electoral rolls, to obtain three cohorts: rural Māori, urban Māori and urban non-Māori. Logistic regression was used to model response rates.Time invested in gaining tribal and health community engagement assisted in the development and design of clear protocols and processes for the study. Response rates were 57.6%, 48.3% and 57.2%. Co-operation rates (participation among those with whom contact was established) were 74.7%, 66.6% and 71.4%.Use of electoral rolls enables straightforward sampling but results in low response rates because electors have moved. Co-operation rates highlight the acceptability of this research project to the participants; they indicate the strength of Kaupapa Māori Methodologies in engaging Māori participants and community.This study provides a model for conducting clinical/biomedical research projects that are compatible with cultural protocols and methodologies, in which the primary aim of the research was Māori health gain.

Background Left ventricular hypertrophy (LVH) is a strong predictor of cardiovascular disease and is common among patients with type 2 diabetes. However, no systematic screening for LVH is currently recommended for patients with type 2 diabetes. The purpose of this study was to determine whether NT-proBNP was superior to 12-lead electrocardiography (ECG) for detection of LVH in patients with type 2 diabetes. Methods Prospective cross-sectional study comparing diagnostic accuracy of ECG and NT-proBNP for the detection of LVH among patients with type 2 diabetes. Inclusion criteria included having been diagnosed for > 5 years and/or on treatment for type 2 diabetes; patients with Stage 3/4 chronic kidney disease and known cardiovascular disease were excluded. ECG LVH was defined as either the Sokolow-Lyon or Cornell voltage criteria. NT-proBNP level was measured using the Roche Diagnostics Elecsys assay. Left ventricular mass was assessed from echocardiography. Receiver operating characteristic curve analysis was carried out and area under the curve (AUC) was calculated. Results 294 patients with type 2 diabetes were recruited, mean age 58 (SD 11) years, BP 134/81 ± 18/11 mmHg, HbA1c 7.3 ± 1.5%. LVH was present in 164 patients (56%). In a logistic regression model age, gender, BMI and a history of hypertension were important determinants of LVH (p < 0.05). Only 5 patients with LVH were detected by either ECG voltage criteria. The AUC for NT-proBNP in detecting LVH was 0.68. Conclusions LVH was highly prevalent in asymptomatic patients with type 2 diabetes. ECG was an inadequate test to identify LVH and while NT-proBNP was superior to ECG it remained unsuitable for detecting LVH. Thus, there remains a need for a screening tool to detect LVH in primary care patients with type 2 diabetes to enhance risk stratification and management.

Summary points Congestive heart failure is a common condition that increases in prevalence with increasing age. In 2003, guidance from the National Institute for Health and Clinical Excellence acknowledged that the “rising epidemic of heart failure” is partly the result of people living longer and the more effective treatments for coronary heart disease now available. It also acknowledged, however, that average life expectancy is only about three years after diagnosis, which is much worse than for many other serious illnesses such as cancer of the breast or colon.1 The condition is associated with poor quality of life, frequent hospital admissions, and poor survival,2 although this may have changed with the advent of better treatments. Community estimates of prevalence vary from 1.6 to 4.6 cases per 1000 in men aged 45-74 years and from 0.9 to 2.2 cases per 1000 in women. About 1% of men develop heart failure after age 75 and almost 2% after 80 years.3 This review discusses the immediate management of patients who present with the clinical syndrome of heart failure (usually a combination of dyspnoea, fatigue, exercise intolerance, and fluid …

The study evaluated the use of age-related decision limits for N-terminal pro-B-type natriuretic peptide (NT-proBNP), for ruling out suspected systolic dysfunction in symptomatic patients in primary care, compared with the present standards.Data were obtained from 5508 patients from 10 studies in the UK, New Zealand, Europe, and USA. All have had NT-proBNP analysis and echocardiography. The median age was 62 years (range 18-100 years) with a prevalence of reduced left ventricular systolic function (left ventricular ejection fractionor =40%) of 18%. In a receiver operating characteristic curve analysis, overall area under the curve (AUC) was 0.89. When looking at different age groups, AUC was highest (0.95) for50 years, intermediate (0.90) for 50-75 years, and lowest (0.82) for75 years. Using optimized decision limits, sensitivity, specificity, and negative predictive values (NPVs) were:50 years (50 ng/L): 99.2, 57.2, and 99.7%; 50-75 years (75 ng/L): 95.9, 51.0, and 96.8%; and75 years (250 ng/L): 87.9, 53.7, and 92.4%, respectively. Using only a single decision value (125 ng/L for all ages) gave sensitivities of 89.1, 91.9, and 94.3%; specificities of 84.0, 69.1, and 29.3% and NPVs of 97.7, 97.6, and 93.4%. A decision value of 400 ng/L for all ages gave much lower sensitivities.In a large population of patients in primary care, the use of age-stratified NT-proBNP decision limits considerably improves performance over current standards, with an excellent NPV for exclusion of reduced left ventricular systolic function.

Background— Chromosome 9p21.3 (chr9p21.3) recently was identified by several genome-wide association studies as the genomic region most strongly associated with the risk of coronary artery disease. Within the chr9p21.3 locus, the single-nucleotide polymorphism rs1333049 has been demonstrated to be most strongly associated with susceptibility to developing coronary artery disease. However, the effect of rs1333049 on clinical outcomes in patients with established coronary disease has yet to be determined. Methods and Results— Coronary Disease Cohort Study (CDCS) (n=1054) and Post-Myocardial Infarction (PMI) (n=816) study participants were genotyped for rs1333049. Clinical history, circulating lipids, neurohormones, cardiac function, and discharge medications were documented. All-cause mortality and cardiovascular hospital readmissions were recorded over a median follow-up period of 4.0 years for the CDCS cohort and 9.1 years for the PMI cohort. The CDCS patients homozygous for the high-risk C allele had an age of onset 2 to 5 years earlier for coronary disease ( P =.005), angina ( P =.025), myocardial infarction ( P =.022), and percutaneous transluminal coronary angioplasty ( P =.009). Patients with the CC genotype also had higher levels of total cholesterol ( P =.033) and triglycerides ( P =.003). The PMI participants with the CC genotype were 3 years younger on admission ( P =.009). Cox proportional hazards analysis adjusting for established predictors of increased risk showed no significant association between rs1333049 genotype and mortality in either the CDCS ( P =.214) or the PMI ( P =.696) cohorts. Conclusions— The chr9p21.3 polymorphism rs1333049 was associated with an earlier age of disease onset in 2 coronary disease cohorts but not with poorer clinical outcome in either cohort.

Background. In this study, our main goal was to determine whether an integrated, community-based model of care using culturally appropriate health-care assistants to manage hypertension in Māori and Pacific patients with diabetes and chronic kidney disease (CKD) is more effective than conventional care in achieving blood pressure (BP) targets and delaying progression of cardiac and renal end-organ damage. Methods. Sixty-five Māori and Pacific patients (aged 47-75 years) with type 2 diabetes, moderate CKD (>0.5 g proteinuria/day, serum creatinine 130-300 μmol/l) and hypertension were randomized to usual care (n = 32) or community/intervention care (n = 33) for 12 months. Community care patients were visited monthly by a nurse-led health-care assistant for BP measurement. Antihypertensives were adjusted using a stepwise protocol, aiming for a BP

Aims To describe changes in heart failure (HF) epidemiology in New Zealand between 1988 and 2008 using the number of days alive and out of hospital after a first hospitalization for HF, and to use these data to evaluate the overall impact of changing patterns of hospitalization and survival. Methods and results We performed a population analysis of all HF hospitalization and mortality data from 1 January 1988 to 31 December 2008 in New Zealand. The main outcome measures were: days alive and out of hospital, age standardized hospitalization rates, and mortality after an index hospitalization for HF. The number of days alive and out of hospital at 2 years increased by 2 months over the two decades of the study (from 448.8 to 511.3 days). Age standardized index HF hospitalization rates increased from 1988 to 1999, and declined thereafter, current rates are 106.9/100 000 for women and 174.3/100 000 for men. Patient age at index admission progressively increased, and hospital length of stay decreased. Mortality rates progressively decreased until 2000, but there has been no further decrease since then. Total hospital days have decreased up to 2008. Conclusion There have been major changes in the epidemiology of HF in New Zealand between 1988 and 2008, during which time there have been important changes in HF management. Despite increasing age, hospitalization rates are now declining and patients with HF are surviving longer out of hospital and with fewer hospital days. These results support the need for continued emphasis on delivery of effective community-based care for patients with this long-term condition.

Background— The urocortins are emerging as potentially important contributors to neurohumoral regulation of the circulation with recent reports attributing a powerful array of hemodynamic, renal, and neurohumoral effects to the urocortins in cardiac failure. These peptides also seem to have cardioprotective effects in the setting of ischemia-reperfusion. Little is known concerning the plasma concentrations of the urocortins in health and disease. We have investigated plasma urocortin 1 as a potential diagnostic marker of heart failure and documented its relationships to symptoms, measures of cardiac function, and concurrent levels of other circulating neurohormones. Methods and Results— In 299 patients with recent onset dyspnea or peripheral edema presenting to primary care, plasma urocortin 1 and other vasoactive hormones were assayed, and echocardiography was performed. Heart failure was present in 74 patients (25%) according to predefined diagnostic criteria. Urocortin 1 levels were increased in patients with heart failure and were related to functional class, clinical signs of heart failure, echocardiographic indicators of left ventricular dimensions and function, plasma creatinine, and concurrent circulating levels of plasma natriuretic peptides, adrenomedullin, and endothelin 1. Conclusions— Plasma urocortin 1 is elevated in heart failure (in proportion to the degree of cardiac dysfunction) in concert with the generalized neurohormonal activation seen in this condition. Urocortin levels predict heart failure independent of age, history of previous myocardial infarction, diabetes, hypertension, fractional shortening, and N-terminal prohormone brain natriuretic peptide levels.

Aims Heart failure (HF) with normal or preserved left ventricular (LV) ejection fraction (HFPEF) has been reported to be associated with similar outcome as HF with reduced EF (HFREF) in registry-based and epidemiological analyses, but many of these studies excluded patients who did not have EF measurements. Conversely, prior prospective studies have reported better outcome for patients with HFPEF. We performed a meta-analysis of prospective observational studies comparing all-cause mortality in patients with HFREF and HFPEF. Methods and results We searched several online databases for studies comparing outcome in HFREF and HFPEF, published before 2007. Inclusion criteria: prospective, clinical HF, near complete EF data, and mortality outcome. Review Manager version 4.2.3 software was used for the analysis. Overall, 24 501 patients [9299 deaths (38%)] from 17 studies are included. Average follow-up was 47 months; the HFPEF group was older (69 vs. 66 years) and more likely to be female (44% vs. 26%). Of the 7688 patients with HFPEF 2468 died (32.1%), compared with 6831 of the 16 813 patients with HFREF (40.6%): odds ratio 0.51 (95% CI: 0.48, 0.55). Conclusion This literature-based meta-analysis demonstrates that mortality among patients with HFPEF was half that observed in those with HFREF, in contrast to previous reports suggesting that mortality may be similar between both groups.

OBJECTIVE—To examine the effect of handgrip exercise induced ischaemia on non-invasive assessment of endothelial function in the brachial artery. DESIGN AND SETTING—High frequency ultrasound was used to measure brachial artery diameter at rest and after reactive hyperaemia induced by forearm cuff occlusion with and without handgrip exercise induced ischaemia. SUBJECTS—10 healthy subjects

The ONTARGET and TRANSCEND clinical trials were designed to investigate the cardioprotective effects of telmisartan 80 mg and ramipril 10 mg, alone and in combination, in patients at high risk of cardiovascular disease. Cardiac MRI enables investigation of mechanistic effects of these agents on cardiac structural and functional variables. Here, we report the design, analysis protocol, reproducibility and relevant quality control procedures, and baseline patient characteristics of the ONTARGET/TRANSCEND cardiac MRI substudy. MRI was undertaken in 330 subjects enrolled in ONTARGET, and 38 subjects in TRANSCEND, across eight centers in six countries. Analyses were performed by two independent analysts using guide-point modeling. Cases with discrepancies in LV mass (LVM) of5% were independently reanalyzed. Cases with discrepancies in end-diastolic volume (EDV) of5%, or end-systolic volume (ESV) of12%, were then reconciled by consensus.Baseline characteristics were broadly similar to the main ONTARGET/TRANSCEND trials, except for a higher frequency of coronary artery disease and Asian ethnicity in the substudy. Reproducibility of MRI analyses (mean +/- SD) were 2.8 +/- 3.7 ml in EDV, -0.3 +/- 3.6 ml in ESV, 3.1 +/- 3.3 ml in SV, 1.1 +/- 1.8% in EF, and 0.4 +/- 4.5 g in LVM. Subgroup analyses revealed increased ESV and LVM, and reduced EF, in subjects with a history of either coronary artery disease or myocardial infarction.The ONTARGET/TRANSCEND cardiac MRI substudy protocol provides for a reliable assessment of the effects of telmisartan and ramipril, alone and in combination, on cardiac structural and functional parameters over a 2-year follow-up period.

Background— Restrictive mitral filling pattern (RFP), the most severe form of diastolic dysfunction, is a predictor of outcome after acute myocardial infarction (AMI). Low power has precluded a definite conclusion on the independent importance of RFP, especially when overall systolic function is preserved. We undertook an individual patient meta-analysis to determine whether RFP is predictive of mortality independently of LV ejection fraction (LVEF), end-systolic volume index, and Killip class in patients after AMI. Methods and Results— Twelve prospective studies (3396 patients) assessing the relationship between prognosis and Doppler echocardiographic LV filling pattern in patients after AMI were included. Individual patient data from each study were extracted and collated into a single database for analysis. RFP was associated with higher all-cause mortality (hazard ratio, 2.67; 95% CI, 2.23 to 3.20; P 53%; P P =0.42). RFP also predicted mortality in patients with above- and below-median end-systolic volume index (1575 patients) and in different Killip classes (1746 patients). Importantly, when diabetes, current medication, and prior AMI were included in the model, RFP remained an independent predictor of outcome. Conclusions— Restrictive filling is an important independent predictor of mortality after AMI regardless of LVEF, end-systolic volume index, and Killip class.

Objective The study objective was to more precisely evaluate the link between the pseudonormal mitral filling pattern and death by way of systematic review and meta-analysis. Methods Patients with heart failure (HF) and coronary artery disease (CAD) were included. Online databases were searched for prospective studies of patients with HF and CAD who had comprehensive echocardiography. Mortality in patients with pseudonormal filling was compared with restrictive filling and other nonrestrictive filling patterns, including normal and abnormal relaxation. Review Manager Version 4.2.7 software was used for the analysis. Results Seven studies (5 HF and 2 CAD) were identified, and 887 patients (244 deaths) were included. The pseudonormal filling pattern conferred a 4-fold increase in odds of death compared with abnormal relaxation/normal (odds ratio 4.46; 95% confidence interval, 2.87-6.92). Outcome was similar when restrictive filling was compared with pseudonormal filling (odds ratio 1.16; 95% confidence interval, 0.78-1.74). Death was the main outcome measure. Conclusion This literature-based meta-analysis, pooling results from 7 prospective studies, demonstrates the 4-fold increase in odds of death associated with pseudonormal filling compared with abnormal relaxation/normal. The pseudonormal filling pattern and restrictive filling pattern are associated with similar risk of death. These data further support the need for a comprehensive assessment of diastolic filling, including assessment for pseudonormal filling, as part of routine echocardiographic risk stratification in patients with HF and CAD.

Polymorphisms of the angiotensin-converting enzyme 2 (ACE2) gene, which is located on the X chromosome, have been associated with hypertension and left ventricular hypertrophy in previous studies. We tested the hypothesis that the rare allele of an ACE2 gene polymorphism was associated with risk factors for and adverse outcome after acute coronary syndrome (ACS) events.Patients (n = 1,042) were recruited after admission for an ACS event and were genotyped for the A1075G polymorphism of the angiotensin-converting enzyme 2 gene. This genetic marker was tested for association with baseline measurements, echocardiographic measurements, and clinical outcome, over a median 2.19 years follow-up. As the ACE2 gene is X-linked, analyses were performed separately for males and females. Patients were predominantly of European ethnicity (90.1%).The A1075 allele was significantly associated with covariate-adjusted mortality in male patients (hazard ratio 1.95, 95% CI 1.10-3.46, P = .047) but not unadjusted (hazard ratio 1.14, 95% CI 0.736-1.76, P = .56). The G1075 (P.035) allele was more frequent in patients of Maori compared to European ancestry. E/E', an echocardiographic index of left ventricular diastolic function and filling pressure, was higher in males in the A1075 group (G allele group 10.5 [95% CI 10.0-11.0], A allele group 11.4 [95% CI 10.8-12.1], P = .024). A1075 genotype was significantly associated with male survival in the absence of (mortality: A 12.8%, n = 39; G 29.2%, n = 48; P = .037) but not in the presence of beta-blocker treatment (mortality: A 13.5% n = 273; G 8.2% n = 304, P = nonsignificant).The A1075 allele was associated with covariate-adjusted mortality in male patients.

Objective To determine the effect of calcium supplementation on myocardial infarction, stroke, and sudden death in healthy postmenopausal women. Design Randomised, placebo controlled trial. Setting Academic medical centre in an urban setting in New Zealand. Participants 1471 postmenopausal women (mean age 74): 732 were randomised to calcium supplementation and 739 to placebo. Main outcome measures Adverse cardiovascular events over five years: death, sudden death, myocardial infarction, angina, other chest pain, stroke, transient ischaemic attack, and a composite end point of myocardial infarction, stroke, or sudden death. Results Myocardial infarction was more commonly reported in the calcium group than in the placebo group (45 events in 31 women v 19 events in 14 women, P=0.01). The composite end point of myocardial infarction, stroke, or sudden death was also more common in the calcium group (101 events in 69 women v 54 events in 42 women, P=0.008). After adjudication myocardial infarction remained more common in the calcium group (24 events in 21 women v 10 events in 10 women, relative risk 2.12, 95% confidence interval 1.01 to 4.47). For the composite end point 61 events were verified in 51 women in the calcium group and 36 events in 35 women in the placebo group (relative risk 1.47, 0.97 to 2.23). When unreported events were added from the national database of hospital admissions in New Zealand the relative risk of myocardial infarction was 1.49 (0.86 to 2.57) and that of the composite end point was 1.21 (0.84 to 1.74). The respective rate ratios were 1.67 (95% confidence intervals 0.98 to 2.87) and 1.43 (1.01 to 2.04); event rates: placebo 16.3/1000 person years, calcium 23.3/1000 person years. For stroke (including unreported events) the relative risk was 1.37 (0.83 to 2.28) and the rate ratio was 1.45 (0.88 to 2.49). Conclusion Calcium supplementation in healthy postmenopausal women is associated with upward trends in cardiovascular event rates. This potentially detrimental effect should be balanced against the likely benefits of calcium on bone. Trial registration Australian Clinical Trials Registry ACTRN 012605000242628.

Background— We describe the first human experience with a permanently implantable, direct left atrial pressure (LAP) monitoring system in ambulatory patients with chronic heart failure. Methods and Results— Eight patients with established heart failure and at least 1 heart failure hospitalization or unplanned visit for parenteral therapy in the last year underwent device implantation under fluoroscopic guidance. All subjects received aspirin 150 mg and clopidogrel 75 mg daily. Subjects measured LAP twice daily and attended a clinic regularly for data upload and device calibration. Right heart catheterization was performed at the time of device implantation and at 12 weeks. The device was implanted in all subjects with no procedural complications. At the 12-week follow-up, 87% of device LAP measurements were within ±5 mm Hg of simultaneous pulmonary capillary wedge pressure readings over a wide range of pressures (1.6 to 71 mm Hg). Net drift corrected by calibration was −0.2±1.9 mm Hg/mo. During short-term follow-up, there were no device-related complications or systemic emboli. There were no deaths, no unplanned heart failure clinic visits, and no admissions for heart failure. Conclusions— Ambulatory monitoring of direct LAP with a new implantable device was well tolerated, feasible, and accurate at a short-term follow-up. Further follow-up and investigation are warranted to evaluate the clinical utility of LAP monitoring in patients with heart failure.

Introduction Echocardiographic left ventricular (LV) size and structure are commonly indexed to body surface area (BSA) to adjust for body size. However, BSA may not be the optimal variable to adjust measurements to. While previous studies have demonstrated that the best determinant of LV mass is fat free mass (FFM), the relationship of LV volumes with body composition is uncertain. Objectives To determine the relationships between LV size and body composition. Methods Normal subjects (Caucasian, Maori, Samoan, Chinese and Indian ethnicity) free of cardiac disease underwent medical history, ECG, blood test (cholesterol/glucose), echocardiography for LV volumes (2D biplane methods of discs) and DEXA scans (body composition). Results 166 subjects were assessed: 96 (56%) were women, median age 26yrs, mean BMI 25.4 (SD 6.0), BSA 1.85m 2 (SD 0.28), LVEDV 88ml (SD 27), LVESV 33ml (SD 14). Significant correlations were observed between LV size and measures of body size in all ethnic groups. However, FFM was the best independent predictor of LV volumes (LVEDV partial R 2 0.48 – 0.60). Body size was smallest among Asian subjects and highest among Maori & Samoan subjects. A significant difference in unindexed LVEDV was observed across the groups which persisted when indexed to BSA or height (all P ). Conclusions Among normal subjects LV size is strongly related to FFM. Indexing LV volumes to FFM largely eliminated the differences in LVEDV between subjects with varying body composition. Reference and partition values for normal LV size should be based on LV volumes indexed to fat free mass.

Although brain natriuretic peptide (BNP) and E/Ea are closely related in heart failure (HF) patients and may be helpful to guide HF therapy, the response of E/Ea to changes in BNP over several weeks of intensive HF treatment optimisation is unknown. This study was designed to investigate this relationship.In 17 patients with decompensated HF, treatment was titrated to reduce the NT-proBNP level to200pg/mL over 10 weeks. Paired NT-proBNP measurements and echocardiograms were performed at two weekly intervals during the study. Treatment titration was associated with a reduction in E/Ea (17.6+/-6.8S.D. to 13.7+/-5.0S.D., p=0.018) in keeping with the reduction in NT-proBNP (median 603 [S.E. 561] to 311 [S.E. 235], p=0.045). This relationship remained in those who responded to titration (reduction in NT-proBNP ofor=50%), and those who did not. The overall change in E/Ea was similar to the changes observed in NT-proBNP in each group however there appeared to be temporal differences in the changes in E/Ea and NT-proBNP.This pilot study demonstrates that the E/Ea decreases after NT-proBNP guided HF therapy. E/Ea may be a complementary target for HF therapy optimisation; this hypothesis should be further evaluated in larger scale randomised trials.

e15605 Background: Dovitinib is an anti-VEGFR tyrosine kinase inhibitor (TKI) which also inhibits FGFR-1,-2,-3 and PDGFRβ. VEGFR inhibitors are known to cause cardiotoxicity. We sought to assess th...

Background There is a genetic contribution to the risk of ventricular arrhythmias in survivors of acute coronary syndromes (ACS). We wished to explore the role of 33 candidate single nucleotide polymorphisms (SNPs) in prolonged repolarization and sudden death in patients surviving ACS. Methods A total of 2,139 patients (1680 white ethnicity) surviving an admission for ACS were enrolled in the prospective Coronary Disease Cohort Study. Extensive clinical, echocardiographic, and neurohormonal data were collected for 12 months, and clinical events were recorded for a median of 5 years. Each SNP was assessed for association with sudden cardiac death (SCD)/cardiac arrest (CA) and prolonged repolarization at 3 time-points: index admission, 1 month, and 12 months postdischarge. Results One hundred six SCD/CA events occurred during follow-up (6.3%). Three SNPs from 3 genes (rs17779747 [ KCNJ2 ], rs876188 [ C14orf64 ], rs3864180 [ GPC5 ]) were significantly associated with SCD/CA in multivariable models (after correction for multiple testing); the minor allele of rs17779747 with a decreased risk (hazard ratio [HR] 0.68 per copy of the minor allele, 95% CI 0.50-0.92, P = .012), and rs876188 and rs386418 with an increased risk (HR 1.52 [95% CI 1.10-2.09, P = .011] and HR 1.34 [95% CI 1.04-1.82, P = .023], respectively). At 12 months postdischarge, rs10494366 and rs12143842 ( NOS1AP ) were significant predictors of prolonged repolarization (HR 1.32 [95% CI 1.04-1.67, P = .022] and HR 1.30 [95% CI 1.01-1.66, P = .038], respectively), but not at earlier time-points. Conclusion Three SNPs were associated with SCD/CA. Repolarization time was associated with variation in the NOS1AP gene. This study demonstrates a possible role for SNPs in risk stratification for arrhythmic events after ACS.

Background: Brain Natriuretic Peptide (BNP) has established roles in managing patients with heart failure (HF). Currently, BNP testing is laboratory-based and turnaround time can delay patient management. Point-of-care testing (POCT) potentially allows efficient integration of BNP results with clinical decision-making. The aim of this study was to assess the utility of two POC devices in a HF clinic. Methods: Two POCT devices (A/B) were evaluated to test BNP as part of usual clinical care. DeviceA: venous blood samples were sent for laboratory analysis (Lab-BNP) and capillary samples for POCT (POCT-BNP). DeviceB: capillary and venous samples were obtained. Data analysis: a) consistency between BNP results based on reference levels used in HF management; b) correlation between results. Results: For DeviceA, there was consistency between labBNP and POCT-BNP for 14/20 patients. For the remaining six: one elderly patient with CKD had POCT-BNP inconsistent with lab-BNP, 4 had instrument errors and one had no Lab-BNP performed. For DeviceB, 10 patients were evaluated, there was excellent correlation between capillary and venous BNP (r = 0.97), all of the paired results were similar for utility in HF management. Conclusion: DeviceA, BNP results were similar to laboratory results regarding clinical utility. However DeviceA was unable to integrate data into the hospital systems. DeviceB integrates with hospital systems and has other clinical indications and we have shown excellent correlation between capillary and venous samples. Ease of use with POCT-BNP allows for rapid patient assessment in a HF clinic.

Objective: To determine, through a systematic review and meta-analysis, the magnitude of the survival deficit associated with a restrictive filling pattern after acute myocardial infarction (AMI). Methods: Online databases were searched for prospective echocardiography outcome studies of patients after AMI. All authors were contacted to seek confirmation of their data. Restrictive filling was compared with all non-restrictive filling patterns. Review Manager Version 4.2.7 software was used for analysis. Results: 3855 patients in 16 studies were identified. Follow up varied from two weeks to five years (> 1 year, 10 studies; and > 4 years, four studies). 776 (20%) of patients had a restrictive filling pattern at baseline. 580 patients died (247 in the restrictive group), and the overall odds ratio for death (restrictive filling worse) was 4.10 (95% confidence interval 3.38 to 4.99). Conclusions: Mortality is about four times higher in patients with a restrictive filling pattern than in those with non-restrictive filling patterns after AMI. Echocardiographic assessment of diastolic filling pattern is an important part of the echocardiographic assessment of patients after myocardial infarction and provides important prognostic information about such patients.

The number of patients with newly diagnosed heart failure continues to grow worldwide, to some extent reflecting the increase in survival after acute coronary syndromes and the aging of the population. The search for new and effective therapies for this condition remains a priority in the 21st century. The use of beta-blockers is now well established in the clinical context of mild and moderate systolic heart failure. The effects of beta-blockade on mortality are additive to those with angiotensin-converting enzyme inhibitor therapy. Recently completed, large, randomized trials provided strong evidence for the use of beta-blockers in severe (NYHA functional class IV) heart failure and in asymptomatic patients with left ventricular systolic dysfunction and recent myocardial infarction. Obviously, patient selection still remains the key to the safe use of beta-blockers in patients with heart failure. Further data from clinical trials have emerged to support similar benefits in terms of mortality and morbidity, a good safety record, and tolerability in patients at extremes of age (children and adults70 years of age) and in specific clinical circumstances (including diabetes, chronic obstructive airways disease, renal failure, and atrial fibrillation). Recent use of beta-blockers with vasodilatory properties in patients with heart failure and preserved systolic function (so-called diastolic heart failure) appears promising but will require large-scale, long-term trials prior to widespread clinical use.

Objective Heart failure is associated with poor prognosis and the differentiation of patients on the basis of diastolic filling patterns helps to identify several groups of patients with incrementally higher risk. However, this is reliant on accurate definition of filling patterns. The aim of this study was to compare preload reduction with contrast-enhanced pulmonary venous Doppler recordings for the correct assessment of diastolic filling pattern. Methods In all, 20 patients with heart failure and 25 healthy volunteers were studied on 2 separate days. Preload reduction was achieved with the Valsalva maneuver (nonstandardized and standardized) and sublingual nitroglycerin. Responses were compared among the 3 methods and the filling patterns obtained on each day with the various methods compared. Results Although pulmonary venous Doppler improved the diastolic classification over mitral Doppler, preload reduction resulted in better classification and improved sensitivity, specificity, and positive and negative predictive values. No advantage was observed for either the standardized Valsalva or pharmacologic preload reduction. Conclusion Preload reduction is an essential part of the assessment of diastolic filling grade in patients with heart failure as it can identify pseudonormal filling (mildly increased filling pressures), reversible restrictive filling (high filling pressures), and nonreversible restrictive filling pattern (very high filling pressures).

Brain natriuretic peptide is a cardiac neurohormone that is secreted by the left ventricle in response to an increase in wall stress. Brain natriuretic peptide has emerged as a neurohormone with multiple roles in heart failure management. This review will discuss the role of brain natriuretic peptide in heart failure diagnosis, prognostic assessment, screening for asymptomatic left-ventricular dysfunction, and in the treatment of heart failure.

In 1,049 patients with stable ischemic heart disease (IHD), brain natriuretic peptide (BNP) and amino terminal pro-brain natriuretic peptide (NTproBNP) correlated closely (r = 0.09, p0.001) and were similarly related to left ventricular ejection fraction (LVEF) (r = -0.50 and -0.46, respectively), age (0.44 and 0.47), and creatinine clearance (-0.51 and -0.51). Receiver-operating characteristic curves for detection of LVEF30% were similar (area under the curves = 0.83 and 0.80, both p0.001), and both peptides had strong negative predictive value (95% and 94%). Both independently predicted all-cause mortality and/or heart failure with closely overlapping event-free survival curves; BNP and NTproBNP display strong, near-identical test performance in ruling about severely reduced LVEF and in prediction of all-cause mortality or heart failure in stable IHD.The aim of this work was to test B-type natriuretic peptides for assessment of function and prognosis in stable ischemic heart disease (IHD) and to compare brain natriuretic peptide (BNP) with amino terminal pro-brain natriuretic peptide (NTproBNP), including the relative effects of age and renal function on test performance.Brain natriuretic peptide and NTproBNP are emerging diagnostic and prognostic markers in heart failure and acute coronary syndromes. Their performance in assessing function and prognosis in stable IHD is unknown. Whether one marker is superior and the relative effects of age and renal function on test performance are uncertain.In 1,049 patients with stable IHD, left ventricular ejection fraction (LVEF) was measured by radionuclide scanning and creatinine clearance estimated by the Cockroft-Gault equation. Age, gender, and body mass index were recorded. Twelve-month all-cause mortality or admission with heart failure was prospectively recorded; BNP and NTproBNP were measured by radioimmunoassay.Brain natriuretic peptide and NTproBNP correlated closely (r = 0.90, p0.001) and had similar relationships to LVEF (r = -0.50 and -0.46, respectively, both p0.001), age (0.44 and 0.47, both p0.001), and creatinine clearance (-0.51 and -0.51, both p0.001). Areas under receiver-operating characteristic curves for detection of LVEF30% were similar (0.83 and 0.80, both p0.001) with strong negative predictive values for both (95% and 94%). Both markers independently predicted the clinical end point with closely overlapping event-free survival curves.In stable IHD, BNP and NTproBNP display strong and near-identical test performance in ruling out severely reduced LVEF and in prediction of all-cause mortality or heart failure despite significant effects of age, gender, and renal function on levels of both markers.