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.

The obesity paradox in heart failure patients with preserved versus reduced ejection fraction: a meta-analysis of individual patient data.

BACKGROUND: In heart failure (HF), obesity, defined as body mass index (BMI) ≥30 kg m(-2), is paradoxically associated with higher survival rates compared with normal-weight patients (the 'obesity paradox'). We sought to determine if the obesity paradox differed by HF subtype (reduced ejection fraction (HF-REF) versus preserved ejection fraction (HF-PEF)). PATIENTS AND METHODS: A sub-analysis of the MAGGIC meta-analysis of patient-level data from 14 HF studies was performed. Subjects were divided into five BMI groups: <22.5, 22.5-24.9 (referent), 25-29.9, 30-34.9 and ≥35 kg m(-2). Cox proportional hazards models adjusted for age, sex, aetiology (ischaemic or non-ischaemic), hypertension, diabetes and baseline blood pressure, stratified by study, were used to examine the independent association between BMI and 3-year total mortality. Analyses were conducted for the overall group and within HF-REF and HF-PEF groups. RESULTS: BMI data were available for 23 967 subjects (mean age, 66.8 years; 32% women; 46% NYHA Class II; 50% Class III) and 5609 (23%) died by 3 years. Obese patients were younger, more likely to receive cardiovascular (CV) drug treatment, and had higher comorbidity burdens. Compared with BMI levels between 22.5 and 24.9 kg m(-2), the adjusted relative hazards for 3-year mortality in subjects with HF-REF were: hazard ratios (HR)=1.31 (95% confidence interval=1.15-1.50) for BMI <22.5, 0.85 (0.76-0.96) for BMI 25.0-29.9, 0.64 (0.55-0.74) for BMI 30.0-34.9 and 0.95 (0.78-1.15) for BMI ≥35. Corresponding adjusted HRs for those with HF-PEF were: 1.12 (95% confidence interval=0.80-1.57) for BMI <22.5, 0.74 (0.56-0.97) for BMI 25.0-29.9, 0.64 (0.46-0.88) for BMI 30.0-34.9 and 0.71 (0.49-1.05) for BMI ≥35. CONCLUSIONS: In patients with chronic HF, the obesity paradox was present in both those with reduced and preserved ventricular systolic function. Mortality in both HF subtypes was U-shaped, with a nadir at 30.0-34.9 kg m(-2).

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.

The association between customised small for gestational age infants and pre-eclampsia or gestational hypertension varies with gestation at delivery.

OBJECTIVES: (1) To describe the association between small for gestational age (SGA) infants and pre-eclampsia (PE) and gestational hypertension (GH) and (2) to determine how this association changes with gestational age at delivery using customised centiles to classify infants as SGA. DESIGN: A retrospective observational study. SETTING: National Women's Hospital, a Tertiary Referral Centre in Auckland, New Zealand. POPULATION: A total of 17 855 nulliparous women delivering between 1992 and 1999. METHODS: A comparison of the number of women with a customised SGA infant, PE and GH according to gestational age at delivery. MAIN OUTCOME MEASURES: The incidence of SGA infants (defined as birthweight <10th customised centile), PE and GH at <34, 34-36(+6) and > or =37 weeks. RESULTS: A total of 1847 (10.3%) infants were SGA, 520 (2.9%) women had PE and 1361 (7.6%) had GH. SGA, PE and GH all occurred more commonly with increasing gestation at delivery with 85%, 62% and 90% of cases delivered at term. In women delivering SGA infants, coexisting PE was more likely to occur among those delivered preterm than at term (38.6% at <34 weeks [relative risk, RR 10.2 95%CI 7.3-14.4], 22.4% at 34-36(+6) weeks [RR 6.0 95%CI 4.1-8.6] and 3.8% at > or =37 weeks [OR 1.0]). Women with preterm PE were more likely to have a SGA infant than women with term PE (57.1% at <34 weeks [RR 3.1 95%CI 2.3-4.2], 31.7% at 34-36(+6) weeks [RR 1.7 95%CI 1.2-2.5]) and 18.3% at > or =37 weeks [OR 1.0]). There was a similar association between GH and SGA infants as gestation advanced (57.6% at <34 weeks [RR 4.8 95%CI 3.4-6.6], 30.5% at 34-36(+6) weeks [RR 2.5 95%CI 1.8-3.5] and 12.1% > or =37 weeks [OR 1.0]). CONCLUSIONS: SGA infants and PE are more likely to coexist in preterm births compared with term births. This is likely to reflect the degree of placental involvement in each disease process.