scholarly journals A heart failure phenotype stratified model for predicting 1-year mortality in patients admitted with acute heart failure: results from an individual participant data meta-analysis of four prospective European cohorts

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuntao Chen ◽  
Adriaan A. Voors ◽  
Tiny Jaarsma ◽  
Chim C. Lang ◽  
Iziah E. Sama ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Decision Making ◽  
Cox Model ◽  
Meta Analysis ◽  
Prognostic Index ◽  
Individual Participant Data ◽  
Mortality Risks ◽  
Baseline Mortality ◽  
Individual Participant ◽  
Stratified Model

Abstract Background Prognostic models developed in general cohorts with a mixture of heart failure (HF) phenotypes, though more widely applicable, are also likely to yield larger prediction errors in settings where the HF phenotypes have substantially different baseline mortality rates or different predictor-outcome associations. This study sought to use individual participant data meta-analysis to develop an HF phenotype stratified model for predicting 1-year mortality in patients admitted with acute HF. Methods Four prospective European cohorts were used to develop an HF phenotype stratified model. Cox model with two rounds of backward elimination was used to derive the prognostic index. Weibull model was used to obtain the baseline hazard functions. The internal-external cross-validation (IECV) approach was used to evaluate the generalizability of the developed model in terms of discrimination and calibration. Results 3577 acute HF patients were included, of which 2368 were classified as having HF with reduced ejection fraction (EF) (HFrEF; EF < 40%), 588 as having HF with midrange EF (HFmrEF; EF 40–49%), and 621 as having HF with preserved EF (HFpEF; EF ≥ 50%). A total of 11 readily available variables built up the prognostic index. For four of these predictor variables, namely systolic blood pressure, serum creatinine, myocardial infarction, and diabetes, the effect differed across the three HF phenotypes. With a weighted IECV-adjusted AUC of 0.79 (0.74–0.83) for HFrEF, 0.74 (0.70–0.79) for HFmrEF, and 0.74 (0.71–0.77) for HFpEF, the model showed excellent discrimination. Moreover, there was a good agreement between the average observed and predicted 1-year mortality risks, especially after recalibration of the baseline mortality risks. Conclusions Our HF phenotype stratified model showed excellent generalizability across four European cohorts and may provide a useful tool in HF phenotype-specific clinical decision-making.

Opportunistic screening for heart failure with natriuretic peptides in patients with atrial fibrillation: a meta-analysis of individual participant data of four screening studies

Heart ◽  
2018 ◽  
Vol 104 (15) ◽  
pp. 1236.1-1237 ◽  
Author(s):  
Sander van Doorn ◽  
Geert-Jan Geersing ◽  
Rogier F Kievit ◽  
Yvonne van Mourik ◽  
Loes C Bertens ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Meta Analysis ◽  
Diagnostic Value ◽  
Community Dwelling ◽  
Individual Participant Data ◽  
Cut Point ◽  
Individual Participant

ObjectiveHeart failure (HF) often coexists in atrial fibrillation (AF) but is frequently unrecognised due to overlapping symptomatology. Furthermore, AF can cause elevated natriuretic peptide levels, impairing its diagnostic value for HF detection. We aimed to assess the prevalence of previously unknown HF in community-dwelling patients with AF, and to determine the diagnostic value of the amino-terminal pro B-type natriuretic peptide (NTproBNP) for HF screening in patients with AF.MethodsIndividual participant data from four HF-screening studies in older community-dwelling persons were combined. Presence or absence of HF was in each study established by an expert panel following the criteria of the European Society of Cardiology. We performed a two-stage patient-level meta-analysis to calculate traditional diagnostic indices.ResultsOf the 1941 individuals included in the four studies, 196 (10.1%) had AF at baseline. HF was uncovered in 83 (43%) of these 196 patients with AF, versus 381 (19.7%) in those without AF at baseline. Median NTproBNP levels of patients with AF with and without HF were 744 pg/mL and 211 pg/mL, respectively. At the cut-point of 125 pg/mL, sensitivity was 93%, specificity 35%, and positive and negative predictive values 51% and 86%, respectively. Only 23% of all patients with AF had an NTproBNP level below the 125 pg/mL cut-point, with still a 13% prevalence of HF in this group.ConclusionsWith a prevalence of nearly 50%, unrecognised HF is common among community-dwelling patients with AF. Given the high prior change, natriuretic peptides are diagnostically not helpful, and straightforward echocardiography seems to be the preferred strategy for HF screening in patients with AF.

scholarly journals Exercise-based cardiac rehabilitation for chronic heart failure: the EXTRAMATCH II individual participant data meta-analysis

2019 ◽  
Vol 23 (25) ◽  
pp. 1-98 ◽  
Author(s):  
Rod S Taylor ◽  
Sarah Walker ◽  
Oriana Ciani ◽  
Fiona Warren ◽  
Neil A Smart ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Exercise Capacity ◽  
Meta Analysis ◽  
Patient Characteristics ◽  
Individual Participant Data ◽  
Significant Difference ◽  
Individual Participant ◽  
The Impact

Background Current national and international guidelines on the management of heart failure (HF) recommend exercise-based cardiac rehabilitation (ExCR), but do not differentiate this recommendation according to patient subgroups. Objectives (1) To obtain definitive estimates of the impact of ExCR interventions compared with no exercise intervention (control) on mortality, hospitalisation, exercise capacity and health-related quality of life (HRQoL) in HF patients; (2) to determine the differential (subgroup) effects of ExCR in HF patients according to their age, sex, left ventricular ejection fraction, HF aetiology, New York Heart Association class and baseline exercise capacity; and (3) to assess whether or not the change in exercise capacity mediates for the impact of the ExCR on final outcomes (mortality, hospitalisation and HRQoL), and determine if this is an acceptable surrogate end point. Design This was an individual participant data (IPD) meta-analysis. Setting An international literature review. Participants HF patients in randomised controlled trials (RCTs) of ExCR. Interventions ExCR for at least 3 weeks compared with a no-exercise control, with 6 months’ follow-up. Main outcome measures All-cause and HF-specific mortality, all-cause and HF-specific hospitalisation, exercise capacity and HRQoL. Data sources IPD from eligible RCTs. Review methods RCTs from the Exercise Training Meta-Analysis of Trials for Chronic Heart Failure (ExTraMATCH/ExTraMATCH II) IPD meta-analysis and a 2014 Cochrane systematic review of ExCR (Taylor RS, Sagar VA, Davies EJ, Briscoe S, Coats AJ, Dalal H, et al. Exercise-based rehabilitation for heart failure. Cochrane Database Syst Rev 2014;4:CD003331). Results Out of the 23 eligible RCTs (4398 patients), 19 RCTs (3990 patients) contributed data to this IPD meta-analysis. There was a wide variation in exercise programme prescriptions across included studies. Compared with control, there was no statistically significant difference in pooled time-to-event estimates in favour of ExCR, although confidence intervals (CIs) were wide: all-cause mortality had a hazard ratio (HR) of 0.83 (95% CI 0.67 to 1.04); HF-related mortality had a HR of 0.84 (95% CI 0.49 to 1.46); all-cause hospitalisation had a HR of 0.90 (95% CI 0.76 to 1.06); and HF-related hospitalisation had a HR of 0.98 (95% CI 0.72 to 1.35). There was a statistically significant difference in favour of ExCR for exercise capacity and HRQoL. Compared with the control, improvements were seen in the 6-minute walk test (6MWT) (mean 21.0 m, 95% CI 1.57 to 40.4 m) and Minnesota Living with Heart Failure Questionnaire score (mean –5.94, 95% CI –1.0 to –10.9; lower scores indicate improved HRQoL) at 12 months’ follow-up. No strong evidence for differential intervention effects across patient characteristics was found for any outcomes. Moderate to good levels of correlation (R 2 trial > 50% and p > 0.50) between peak oxygen uptake (VO2peak) or the 6MWT with mortality and HRQoL were seen. The estimated surrogate threshold effect was an increase of 1.6 to 4.6 ml/kg/minute for VO2peak. Limitations There was a lack of consistency in how included RCTs defined and collected the outcomes: it was not possible to obtain IPD from all includable trials for all outcomes and patient-level data on exercise adherence was not sought. Conclusions In comparison with the no-exercise control, participation in ExCR improved the exercise and HRQoL in HF patients, but appeared to have no effect on their mortality or hospitalisation. No strong evidence was found of differential intervention effects of ExCR across patient characteristics. VO2peak and 6MWT may be suitable surrogate end points for the treatment effect of ExCR on mortality and HRQoL in HF. Future studies should aim to achieve a consensus on the definition of outcomes and promote reporting of a core set of HF data. The research team also seeks to extend current policies to encourage study authors to allow access to RCT data for the purpose of meta-analysis. Study registration This study is registered as PROSPERO CRD42014007170. Funding The National Institute for Health Research Health Technology Assessment programme.

Cardiac rehabilitation for heart failure can improve quality of life and fitness

BMJ ◽  
2019 ◽  
pp. l5456
Author(s):  
Rob Cook ◽  
Peter Davidson ◽  
Rosie Martin
Keyword(s):  
Quality Of Life ◽  
Heart Failure ◽  
Cardiac Rehabilitation ◽  
Meta Analysis ◽  
Health Technology ◽  
Individual Participant Data ◽  
Improve Quality ◽  
Health Technology Assessment Programme ◽  
Individual Participant

The studyTaylor RS, Walker S, Ciani O, et al. Exercise-based cardiac rehabilitation for chronic heart failure: the EXTRAMATCH II individual participant data meta-analysis. Health Technol Assess 2019;23:1-98.This project was funded by the NIHR Health Technology Assessment Programme (project number 15/80/30).To read the full NIHR Signal, go to https://discover.dc.nihr.ac.uk/content/signal-000803/cardiac-rehabilitation-for-heart-failure-can-improve-quality-of-life-and-fitness

scholarly journals External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Kym I. E. Snell ◽  
◽  
John Allotey ◽  
Melanie Smuk ◽  
Richard Hooper ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Prediction Models ◽  
Meta Analysis ◽  
External Validation ◽  
Predictive Performance ◽  
Prognostic Models ◽  
Individual Participant Data ◽  
Net Benefit ◽  
Mortality And Morbidity ◽  
Individual Participant

Abstract Background Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. Methods IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis. Results Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model’s calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%. Conclusions The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice. Trial registration PROSPERO ID: CRD42015029349.

OP91 Individual Participant Data Meta-Analysis Of Exercise Rehabilitation In Heart Failure

2018 ◽  
Vol 34 (S1) ◽  
pp. 33-34
Author(s):  
Oriana Ciani ◽  
Sarah Walker ◽  
Fiona Warren ◽  
Neil Smart ◽  
Massimo Piepoli ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systematic Review ◽  
Meta Analysis ◽  
Aggregate Data ◽  
Controlled Trials ◽  
Individual Participant Data ◽  
Exercise Rehabilitation ◽  
Randomized Controlled ◽  
All Cause Mortality ◽  
Individual Participant

Introduction:Traditional meta-analyses synthesize aggregate data obtained from study publications or study authors, such as a treatment effect estimate and its associated uncertainty. An increasingly important approach is the meta-analysis of individual participant data (IPD) where the raw individual-level data are obtained for each study and used for synthesis. This study compares and discusses results from an IPD meta-analysis vs standard meta-analysis of randomized controlled trials of exercise cardiac rehabilitation in chronic heart failure (CHF).Methods:Based on a previous systematic review, the Exercise Training Meta-Analysis of Trials for Chronic Heart Failure (ExTraMATCH II) identified and collected IPD from randomized controlled trials (RCTs) that compared exercise rehabilitation with a non-exercise control with a minimum follow-up of six months. For this abstract, the outcome of interest was all-cause mortality. Original IPD were checked for consistency and compiled in a master dataset. Standard meta-analytic models were used for aggregate data whilst two-stage and one-stage approaches, accounting for the clustering of participants within studies, were planned for statistical analyses of IPD.Results:Overall thirty-three RCTs were included in the original systematic review, whereas within the ExTraMatch II project, IPD on all-cause mortality were obtained from seventeen RCTs of approximately 3,700 patients. From aggregate data there was no significant difference in pooled mortality (relative risk 0.92, 95% confidence interval 0.67 to 1.26). IPD analysis revealed 701 events across exercise and control groups. Our ongoing IPD analyses will allow us to examine how patients’ characteristics (e.g. age, New York Heart Association functional class, ejection fraction) modify treatment benefit.Conclusions:Given the limitations of current trial level meta-analysis evidence in CHF, access to individual data from several RCTs offers a timely and important opportunity to revisit the question of which CHF patient subgroups benefit most from exercise-based rehabilitation.

scholarly journals APOL1 Kidney Risk Variants and Cardiovascular Disease: An Individual Participant Data Meta-Analysis

2019 ◽  
Vol 30 (10) ◽  
pp. 2027-2036 ◽  
Author(s):  
Morgan E. Grams ◽  
Aditya Surapaneni ◽  
Shoshana H. Ballew ◽  
Lawrence J. Appel ◽  
Eric Boerwinkle ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Meta Analysis ◽  
Individual Participant Data ◽  
Risk Variants ◽  
Individual Participant ◽  
Incident Cardiovascular Disease

BackgroundTwo coding variants in the apo L1 gene (APOL1) are strongly associated with kidney disease in blacks. Kidney disease itself increases the risk of cardiovascular disease, but whether these variants have an independent direct effect on the risk of cardiovascular disease is unclear. Previous studies have had inconsistent results.MethodsWe conducted a two-stage individual participant data meta-analysis to assess the association of APOL1 kidney-risk variants with adjudicated cardiovascular disease events and death, independent of kidney measures. The analysis included 21,305 blacks from eight large cohorts.ResultsOver 8.9±5.0 years of follow-up, 2076 incident cardiovascular disease events occurred in the 16,216 participants who did not have cardiovascular disease at study enrollment. In fully-adjusted analyses, individuals possessing two APOL1 kidney-risk variants had similar risk of incident cardiovascular disease (coronary heart disease, myocardial infarction, stroke and heart failure; hazard ratio 1.11, 95% confidence interval, 0.96 to 1.28) compared to individuals with zero or one kidney-risk variant. The risk of coronary heart disease, myocardial infarction, stroke and heart failure considered individually was also comparable by APOL1 genotype. APOL1 genotype was also not associated with death. There was no difference in adjusted associations by level of kidney function, age, diabetes status, or body-mass index.ConclusionsIn this large, two-stage individual participant data meta-analysis, APOL1 kidney-risk variants were not associated with incident cardiovascular disease or death independent of kidney measures.

Exercise training for chronic heart failure (ExTraMATCH II): Protocol for an individual participant data meta-analysis

2014 ◽  
Vol 174 (3) ◽  
pp. 683-687 ◽  
Author(s):  
Rod S. Taylor ◽  
Massimo F. Piepoli ◽  
Neil Smart ◽  
Andrew J.S. Coats ◽  
Stephen Ellis ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Exercise Training ◽  
Meta Analysis ◽  
Individual Participant Data ◽  
Individual Participant
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