Prognostic significance of anaemia in patients with heart failure with preserved and reduced ejection fraction: results from the MAGGIC individual patient data meta-analysis.

BACKGROUND: Anaemia is common among patients with heart failure (HF) and is an important prognostic marker. AIM: We sought to determine the prognostic importance of anaemia in a large multinational pooled dataset of prospectively enrolled HF patients, with the specific aim to determine the prognostic role of anaemia in HF with preserved and reduced ejection fraction (HF-PEF and HF-REF, respectively). DESIGN: Individual person data meta-analysis. METHODS: Patients with haemoglobin (Hb) data from the MAGGIC dataset were used. Anaemia was defined as Hb < 120 g/l in women and <130 g/l in men. HF-PEF was defined as EF ≥ 50%; HF-REF was EF < 50%. Cox proportional hazard modelling, with adjustment for clinically relevant variables, was undertaken to investigate factors associated with 3-year all-cause mortality. RESULTS: Thirteen thousand two hundred and ninety-five patients with HF from 19 studies (9887 with HF-REF and 3408 with HF-PEF). The prevalence of anaemia was similar among those with HF-REF and HF-PEF (42.8 and 41.6% respectively). Compared with patients with normal Hb values, those with anaemia were older, were more likely to have diabetes, ischaemic aetiology, New York Heart Association class IV symptoms, lower estimated glomerular filtration rate and were more likely to be taking diuretic and less likely to be taking a beta-blocker. Patients with anaemia had higher all-cause mortality (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.25-1.51), independent of EF group: aHR 1.67 (1.39-1.99) in HF-PEF and aHR 2.49 (2.13-2.90) in HF-REF. CONCLUSIONS: Anaemia is an adverse prognostic factor in HF irrespective of EF. The prognostic importance of anaemia was greatest in patients with HF-REF.

Genetic markers of repolarization and arrhythmic events after acute coronary syndromes.

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.

Long-term outcomes in patients with restrictive filling following ST-segment elevation myocardial infarction.

This study evaluated the effect of restrictive filling pattern (RFP) on 5-year outcomes in patients following ST-segment elevation myocardial infarction (STEMI). A hundred STEMI patients treated either by rescue or primary percutaneous coronary intervention with an echocardiogram performed within 6 weeks of STEMI comprised the study group. Creatinine kinase (CK) and left ventricular ejection fraction were independent determinants of RFP, and RFP was an independent predictor of cardiac and all-cause mortality at median follow up of 5 years.

Genetic variation in the renin-angiotensin-aldosterone system is associated with cardiovascular risk factors and early mortality in established coronary heart disease.

This study examined renin-angiotensin-aldosterone (RAAS) system gene variants for associations with cardiovascular risk factors and outcomes in coronary heart disease. Coronary disease patients (n=1186) were genotyped for 21 single-nucleotide polymorphisms (SNPs) within angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin-II type-1 receptor (AGTR1) and aldosterone synthase (CYP11B2). Associations with all-cause mortality and cardiovascular readmissions were assessed over a median of 3.0 years. The AGT M235T 'T' allele was associated with a younger age of clinical coronary disease onset (P=0.006), and the AGT rs2478545 minor allele was associated with lower circulating natriuretic peptides (P=0.0001-P=0.001) and E/E(1) (P=0.018). Minor alleles of AGT SNPs rs1926723 and rs11122576 were associated with more frequent history of renal disease (P0.04) and type-2 diabetes (P0.02), higher body mass index (P0.02) and greater mortality (P0.007). AGT rs11568054 minor allele carriers had more frequent history of renal disease (P=0.04) and higher plasma creatinine (P=0.033). AGT rs6687360 minor allele carriers exhibited worse survival (P=0.02). ACE rs4267385 was associated with older clinical coronary disease onset (P=0.008) and hypertension (P=0.013) onset, increased plasma creatinine (P=0.01), yet greater mortality (P=0.044). Less history of hypertension was observed with the AGTR1 rs12685977 minor allele (P=0.039). Genetic variation within the RAAS was associated with cardiovascular risk factors and accordingly poorer survival.

The larger exercise stroke volume in endurance-trained men does not result from increased left ventricular early or late inflow or tissue velocities.

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), VO(2)peak, stroke volume (CO(2) 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 < 0.001), while measures of atrial systole were increased (P < 0.001) during exercise in older men. Stroke volume during exercise was larger in the trained men (P < 0.001); however, early and late mitral inflow and tissue velocities were not different between trained and untrained men. CONCLUSION: The larger exercise stroke volume in trained older male athletes does not seem to be related to faster filling or lengthening velocities during early or late filling. Thus, a larger, more compliant left ventricle in combination with an increased blood volume may explain the larger LV filling volumes in trained seniors.

Geographic variation in left ventricular mass and mass index: a systematic review.

Left ventricular (LV) hypertrophy, defined as an abnormal increase in LV mass (LVM), is an important prognostic indicator and therapeutic target. LVM is often divided by body surface area to derive indexed mass; however, this does not correctly identify pathological LV hypertrophy in all people, especially when body composition is altered, or in different ethnic groups. We evaluated published ranges of echocardiographic LVM in healthy adult populations from different countries, excluding control groups, and compared them with the American Society of Echocardiography reference ranges. A total of 33 studies met the inclusion criteria. In men and women, there was wide variation in the ranges of LVM with a tendency for the upper limit to increase geographically westward; this variation remained for indexed mass. Several ranges fell outside the upper reference limits: in men, 13 of the mass ranges and 16 of indexed mass; and in women, 8 mass and 16 indexed mass. This review has shown that current guidelines may need revision as some published series suggest that greater LV mass should be considered normal. This may be explained by ethnic differences and supports the need for widely applicable and ethnically diverse reference ranges to be established.

Role of echocardiographic left ventricular mass and carotid intima-media thickness in the cardiovascular risk assessment of asymptomatic patients with type 2 diabetes mellitus.

BACKGROUND: Standard cardiovascular (CV) risk assessment may underestimate risk in people with type 2 diabetes mellitus (T2DM). Cardiac and vascular imaging to detect subclinical disease may augment risk prediction. This study investigated the association between CV risk, left ventricular hypertrophy (LVH) and carotid intima-media thickness (CIMT) in patients with T2DM free of CV symptoms. METHODS: People with T2DM without known CV disease were recruited from general practice. The 5-year risk of CV events was calculated using an adjusted Framingham equation and the prevalence of LVH and abnormal CIMT across bands of CV risk assessed. In those at intermediate risk, the number needed to scan (NNS) to reclassify one person to high risk was calculated across the group and compared in those above and below 55 years. The association between LV mass and CIMT was also assessed. RESULTS: Mean age 57 years (SD11), 51% female. Median 5-year CV risk 14.3% (interquartile range 10.3, 19.5), 51% had LVH (American Society of Echocardiography criteria) and 31% an abnormal CIMT (age and sex criteria). In the 52% at intermediate risk, 37% had LVH and 36% an abnormal CIMT. The NNS was 1.7 using both imaging techniques, 2.7 using cardiac imaging alone or 2.8 using vascular imaging alone. Almost twice as many people >55 years had an abnormal CIMT than those <55 years. CONCLUSIONS: Cardiac and vascular imaging to detect subclinical disease can be used to augment prediction of CV risk in people with T2DM at intermediate risk. The value of reclassifying risk is as yet unproven and requires outcome data from intervention studies.

Atrial fibrillation and the risk of death in patients with heart failure: a literature-based meta-analysis.

BACKGROUND: Heart failure (HF) and atrial fibrillation (AF) are common, associated with significant morbidity and mortality, and frequently coexist. It is uncertain from published data if the presence of AF in patients with HF is associated with an incremental adverse outcome. The aim of this study was to combine the results of all studies investigating prognosis for patients with HF and AF compared with those in sinus rhythm (SR) to asses the mortality risk associated with this arrhythmia. METHODS: Electronic databases were searched (Biological Abstracts, Current Contents, EMBASE, Medline, Medline In-progress, PubMed and Scopus), to 31 December 2006, using the key words congestive heart failure, heart failure, ventricular dysfunction, atrial fibrillation, atrial flutter, sinus rhythm, prognosis, outcome, death and hospitalization. Bibliographies of retrieved publications were hand searched. Studies were eligible if they included a HF population and if outcomes were reported by cardiac rhythm (AF or SR). Studies were reviewed by predetermined protocol (including quality assessment). Data were pooled using a random effects model. RESULTS: Twenty studies were included (from 3380 initially identified) representing 32946 patients (10819 deaths). Nine randomized controlled trials (RCT) were included. The prevalence of AF was 15%, crude mortality rates were 46% (AF) and 33% (SR). The odds ratio for death was 1.33 (95% confidence interval (CI) 1.12-1.59) for AF compared with SR. Eleven observational studies were included. The prevalence of AF was 23%, crude mortality rates were 38% (AF) and 25% (SR). The odds ratio for death was 1.57 (95% CI 1.20-2.05) for AF compared with SR. CONCLUSION: This meta-analysis demonstrates that AF is associated with worse outcomes for patients with HF compared with those with SR. Further research is required to determine whether the adverse outcome associated with AF is related to the arrhythmia itself, or to variables, such as HF severity, patient age and comorbidity.

Independence of restrictive filling pattern and LV ejection fraction with mortality in heart failure: an individual patient meta-analysis.

BACKGROUND: The Doppler echocardiographic restrictive mitral filling pattern (RFP) is an important prognostic indicator in patients with heart failure (HF), but the interaction between RFP, left ventricular ejection fraction (LVEF) and filling pattern remains uncertain. AIMS: To determine whether the RFP is predictive of mortality independently of LVEF in patients with HF. METHODS: Online databases were searched to identify studies assessing the relationship between prognosis and LV filling pattern in patients with HF. Individual patient data from 18 studies (3540 patients) were extracted and collated at the MeRGE Coordinating Centre (The University of Auckland). RESULTS: Overall, RFP was associated with higher all-cause mortality than the non-restrictive filling pattern: hazard ratio 2.42 (95% CI 2.06, 2.83). In multivariable analysis the RFP, LVEF, NYHA class and age were independent predictors of mortality. The prevalence of the RFP was inversely related to LVEF but remained a predictor of mortality even in those patients with preserved LVEF. CONCLUSIONS: The restrictive mitral filling pattern is a powerful predictor of mortality, independent of LVEF and age, in patients with HF. Doppler-derived LV filling patterns are an accessible marker from echocardiography that can readily be incorporated in risk stratification of all patients with HF.

Independent prognostic importance of a restrictive left ventricular filling pattern after myocardial infarction: an individual patient meta-analysis: Meta-Analysis Research Group in Echocardiography acute myocardial infarction.

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<0.001) and remained an independent predictor in multivariate analysis with age, gender, and LVEF. The overall prevalence of RFP was 20% but was highest (36%) in the quartile of patients with lowest LVEF (<39%) and lowest (9%) in patients with the highest LVEF (>53%; P<0.0001). RFP remained significant within each quartile of LVEF, and no interaction was found for RFP and LVEF (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.

Restrictive diastolic filling predicts death after acute myocardial infarction: systematic review and meta-analysis of prospective studies.

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.

Serum IGF-I levels are similar in Samoan, Maori and European populations despite differences in body composition.

OBJECTIVE: To determine if serum IGF-I concentrations are similar in healthy adult subjects from the Samoan, Maori and European populations in New Zealand. DESIGN: Serum IGF-I concentration was measured in 75 healthy adults, aged 18-50 years, of Samoan (n=23), Maori (n=22) and European (n=30) descent. Body composition was assessed using standard anthropomorphic measures. In addition all subjects had body composition assessed by Dual energy X-ray absorptiometry (DXA). RESULTS: Weight, body mass index (BMI), and fat mass were significantly greater in Maori and Samoan subjects than European subjects (ANOVA p=0.006, p=0.0003, p=0.03, respectively). However, serum IGF-I concentration was similar between the groups (European 186.8 SEM 14.9 microg/l, Maori 204.8 SEM 17.1 microg/l, Samoan 180.0 SEM 17.5 microg/l, p=0.58). IGF-I levels were similar between ethnic groups after adjustment (ANCOVA) for age, sex or BMI (p=0.5) or age, sex and fat mass (p=0.44). In multivariate analysis the only independent predictor of IGF-I was age (p<0.001) and explained 22% of the variance in IGF-I level. CONCLUSIONS: Serum IGF-I concentrations were similar in Maori, Samoan and European population groups in New Zealand, despite significant differences in anthropomorphic variables and body composition.

Uptake of self-management strategies in a heart failure management programme.

BACKGROUND: Multidisciplinary heart failure programs including patient education and self-management strategies such as daily recording of body weight and use of a patient diary decrease hospital readmissions and improve quality of life. However, the degree of uptake of individual components of these programs and their contribution to patient benefit are uncertain. METHODS: Patients with heart failure admitted to Auckland Hospital were randomised into the management or usual care groups of the Auckland heart failure management study (AHFMS). Patients in the management group were given a heart failure diary for the recording of daily weights, attended a heart failure clinic and were encouraged to attend three education sessions. Patients in the usual care group received routine clinical care, mainly from general practitioners. Patients were followed to 12 months. This study investigated the uptake of self-management by assessing diary use and self-weighing behaviour in the group receiving the heart failure intervention, and compared the level of knowledge of heart failure self-management of the management group to the control group after 12 months. RESULTS: Of the 197 patients in the AHFMS, 100 patients were included in the management group and received a diary and education about heart failure self-management including monitoring weight daily. Of these patients, 76 patients used the diary. These patients were on more medication; were more likely to attend the education sessions, heart failure clinic, and primary care, and had a lower mortality rate over the course of the study. Variables independently associated with use of the diary included less severe symptoms (OR 15, 95% confidence intervals 1.7, 144), frequent attendance at the heart failure clinic (OR 15, 95% CI 3, 78) and attendance at an education session (OR 8, 95% CI 1.5, 42). Of the 76 patients who used the diary, 51 weighed themselves regularly. More of these patients owned scales at home; they were also more likely to attend the education sessions, and experienced fewer hospital admissions than those patients who did not weigh themselves regularly. Variables independently associated with regular self-weighing included the presence of scales at home (OR 6.3, 95% CI 1.7, 14.1), left ventricular ejection fraction >30% (OR 4.3, 95% CI 1.1, 17.5), and attendance at the education session(s) (OR 6.3, 95% CI 1.7, 14.1). Patients in the management group exhibited higher levels of knowledge at 12 months of follow-up and were more likely to monitor their condition using daily weighing, compared to the control group. CONCLUSIONS: At 12 months of follow-up, implementation of self-management strategies including daily weight monitoring and level of education on self-management was significantly higher in the management group than the control group. For the patients in the management group, not using the diary or inability to perform daily weighing were associated with less frequent attendance at the heart failure clinic and education sessions and poorer health outcomes. In this study, attendance at the education sessions was associated with the adoption of self-management, underlining the importance of education in multidisciplinary heart failure programmes. Self-weighing could be increased by provision of scales to all patients. The subset of patients who did not adopt self-management strategies in this study were at high risk of death or readmission.

Randomized, controlled trial of integrated heart failure management: The Auckland Heart Failure Management Study.

AIMS: To determine the effect of an integrated heart failure management programme, involving patient and family, primary and secondary care, on quality of life and death or hospital readmissions in patients with chronic heart failure. METHODS AND RESULTS: This trial was a cluster randomized, controlled trial of integrated primary/secondary care compared with usual care for patients with heart failure. The intervention involved clinical review at a hospital-based heart failure clinic early after discharge, individual and group education sessions, a personal diary to record medication and body weight, information booklets and regular clinical follow-up alternating between the general practitioner and heart failure clinic. Follow-up was for 12 months. One hundred and ninety-seven patients admitted to Auckland Hospital with an episode of heart failure were enrolled in the study. There was no significant difference between the intervention and control groups for the combined end-point of death or hospital readmission. The physical dimension of quality of life showed a greater improvement in the intervention group from baseline to 12 months compared with the control group (-11.1 vs -5.8 respectively, 2 P=0.015). The main effect of the intervention was attributable to the prevention of multiple admissions (56 intervention group vs 95 control group, 2 P=0.015) and associated reduction in bed days. CONCLUSIONS: This integrated management programme for patients with chronic heart failure improved quality of life and reduced total hospital admissions and total bed days.

Effects of improved glycaemic control on endothelial function in patients with type 2 diabetes.

BACKGROUND: Patients with type 2 diabetes have abnormal endothelial function but it is not certain whether improvements in glycaemic control will improve endothelial function. AIMS: To examine the effects of short-term improved glycaemic control on endothelial function in patients with inadequately regulated type 2 diabetes mellitus. METHODS: Forty-three patients with type 2 diabetes and glycosylated haemoglobin (HbA1c) > 8.9% were randomized to either improved glycaemic control (IC) n = 21 or usual glycaemic control (UC) n = 22 for 20 weeks. Using high-resolution B-mode ultrasound, brachial artery flow-mediated dilatation (FMD) and glyceryl trinitrate-mediated dilatation (GTN-D) were measured at baseline and 20 weeks later. RESULTS: After 20 weeks, HbA1c was significantly lower in IC versus UC (IC 8.02 +/- 0.25% versus UC 10.23 +/- 0.23%, P < 0.0001) but changes in FMD and GTN-D were not different between the groups (FMD at baseline and week 20 IC 5.1 +/- 0.56% versus 4.9 +/- 0.56% and UC 4.2 +/- 0.51% versus 3.1 +/- 0.51%; P = 0.23: GTN-D IC 12.8 +/- 1.34% versus 10.4 +/- 1.32% and UC 13.7 +/- 1.2% versus 12.7 +/- 1.23%; P = 0.39). In the IC group weight increased by 3.2 +/- 0.8 kg after 20 weeks compared to 0.02 +/- 0.70 kg in UC (P = 0.003). Blood pressure and serum lipid concentrations did not change in either group. CONCLUSIONS: Short-term reduction of HbA1c levels did not appear to affect endothelial function in patients with type 2 diabetes and previously poorly regulated glycaemic control.

Comparison of ultrasound assessment of flow-mediated dilatation in the radial and brachial artery with upper and forearm cuff positions.

In the published literature relating to flow-mediated dilatation (FMD), there are substantial differences between centres in terms of normal FMD amongst healthy subjects. This present study attempts to identify the effect of differing methodologies on FMD. High frequency ultrasound was used to measure blood flow and percentage brachial and radial artery dilatation after reactive hyperaemia induced by forearm or upper arm cuff occlusion in 24 healthy subjects, less than 40 years, without known cardiovascular risk factors. FMD of the brachial artery was significantly higher after upper arm occlusion, compared with forearm occlusion, 6.4 (3.3) and 3.9 (2.6)% (P<0.05), respectively. FMD of the radial artery was significantly higher after forearm occlusion, compared with upper arm occlusion, 10.0 (4.6) and 7.9 (3.5)% (P<0.05), respectively. The percentage blood flow increase in the brachial and radial arteries after forearm and upper arm occlusion were similar. After forearm and upper arm occlusion, the radial artery percentage dilatation was greater than the brachial artery. In conclusion dilatation of the brachial artery, after reactive hyperaemia induced by upper arm occlusion, was significantly more pronounced compared with dilatation of the brachial artery after forearm occlusion, despite a similar percentage blood flow increase. The local ischaemia of the brachial artery with a proximal occlusion may explain why the brachial artery dilated more after upper arm occlusion compared with after forearm occlusion. The study has also shown that FMD of the radial artery could be assessed by B-mode ultrasound technique. FMD was greater using the radial artery compared with the brachial artery, suggesting that the radial artery may be a useful way to assess FMD in future clinical studies.

The effect of acute hyperglycaemia on brachial artery flow mediated dilatation in normal volunteers.

BACKGROUND: Endothelial function is known to be abnormal in patients with diabetes and acute hyperglycaemia may play an aetiological role. AIMS: The aim of this randomised controlled study was to determine if acute systemic hyperglycaemia impairs endothelial function in normal subjects. METHODS: Endothelial function was assessed by the change in brachial artery diameter in response to forearm ischaemia using B-mode ultrasound in ten healthy subjects (eight male) aged 19-35 years. Brachial artery blood flow velocity and diameter were measured before and after five minutes of forearm ischaemia. Measurements were performed in the supine position after an overnight fast, before and after 60 minute infusions of 0.9% saline or 10% dextrose. Measurements were made on two separate occasions at least 24 hours apart, and subjects were randomised to saline first or dextrose first. The largest diameter measured after ischaemia was divided by the resting arterial diameter to calculate percent dilatation of the artery from baseline, and is reported as flow-mediated dilatation (FMD). RESULTS: Dextrose infusion resulted in a significant rise in mean (SD) serum glucose 5.2 (0.1) to 9.2 (0.3) mmol/L and insulin concentration 6.3 (1.4) to 20.6 (3.7) mU/L p<0.002. Brachial artery blood flow velocity and diameter increased significantly from baseline after ischaemia (p<0.002). Mean FMD (SEM) before and after infusion were not, however, significantly different (p=0.4) (pre-saline 7.3 [1.0]%, post saline 5.2 [1.5]% and predextrose 8.1 [2.0]%, post dextrose 5.9 [1.7]%). CONCLUSIONS: These data suggest that acute hyperglycaemia does not impair FMD in normal subjects.

Effects of carvedilol on left ventricular regional wall motion in patients with heart failure caused by ischemic heart disease. Australia-New Zealand Heart Failure Research Collaborative Group.

BACKGROUND: Beta-blocker therapy has been shown to improve left ventricular (LV) ejection fraction and reduce LV volumes in patients with heart failure caused by ischemic heart disease. However, the possible mechanisms of this improvement and the effects of such treatment on regional wall motion have not been established. In a substudy of the Australia-New Zealand trial of carvedilol in patients with heart failure caused by ischemic heart disease, the effects of treatment on LV regional wall motion were assessed using 2-dimensional echocardiography. METHODS AND RESULTS: One hundred nineteen patients from 10 centers were included on this substudy. Patients were randomly assigned to treatment with carvedilol or placebo. Echocardiography was performed before randomization and after 6 and 12 months of treatment. LV regional wall motion was assessed using a semiquantitative scoring system. LV wall motion score index (WMSI) was reduced from 2.40 to 2.29 after 6 and 12 months in the carvedilol group and remained unchanged in the placebo group (2-tailed P = .005, carvedilol vs placebo). The percentage of myocardium with normal function also significantly improved with carvedilol treatment. CONCLUSIONS: Carvedilol improved LV regional WMSI in patients with heart failure caused by ischemic heart disease. These results indicate a mechanism by which beta-blocker therapy may benefit patients with heart failure and are consistent with an intrinsic improvement in LV function after treatment with carvedilol.

Does a glass of red wine improve endothelial function?

AIMS: To examine the acute effect of red wine and de-alcoholized red wine on endothelial function. METHODS AND RESULTS: High frequency ultrasound was used to measure blood flow and percentage brachial artery dilatation after reactive hyperaemia induced by forearm cuff occlusion in 12 healthy subjects, less than 40 years of age, without known cardiovascular risk factors. The subjects drank 250 ml of red wine with or without alcohol over 10 min according to a randomized procedure. Brachial artery dilatation was measured again 30 and 60 min after the subjects had finished drinking. The subjects were studied a second time within a week of the first study in a cross-over design. After the red wine with alcohol the resting brachial artery diameter, resting blood flow, heart rate and plasma-ethanol increased significantly. After the de-alcoholized red wine these parameters were unchanged. Flow-mediated dilatation of the brachial artery was significantly higher (P<0.05) after drinking de-alcoholized red wine (5.6+/-3.2%) than after drinking red wine with alcohol (3.6+/-2.2%) and before drinking (3.9+/-2.5%). CONCLUSION: After ingestion of red wine with alcohol the brachial artery dilated and the blood flow increased. These changes were not observed following the de-alcoholized red wine and were thus attributable to ethanol. These haemodynamic changes may have concealed an effect on flow-mediated brachial artery dilatation which did not increase after drinking red wine with alcohol. Flow-mediated dilatation of the brachial artery increased significantly after de-alcoholized red wine and this finding may support the hypothesis that antioxidant qualities of red wine, rather than ethanol in itself, may protect against cardiovascular disease.