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 ◽  
...  

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.

2014 ◽  
Vol 174 (3) ◽  
pp. 683-687 ◽  
Author(s):  
Rod S. Taylor ◽  
Massimo F. Piepoli ◽  
Neil Smart ◽  
Andrew J.S. Coats ◽  
Stephen Ellis ◽  
...  

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuntao Chen ◽  
Adriaan A. Voors ◽  
Tiny Jaarsma ◽  
Chim C. Lang ◽  
Iziah E. Sama ◽  
...  

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.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Howard M Julien ◽  
Preetika Muthukrishnan ◽  
Eldrin F Lewis

Anemia is common in heart failure (HF) patients and has been well-established as a risk factor for increased risk of HF hospitalization and mortality. Treatment with erythropoietin stimulating agents (ESA) has increased hemoglobin, but outcomes trials are limited and use of ESA has been controversial given disparate results in other populations. This meta-analysis aimed to evaluate the impact of ESA and iron on outcomes in HF patients. A systematic review of four databases was conducted in April 2008 (n = 95 unique trials). Analysis inclusion criteria included randomized controlled trial to ESA/iron with clinically defined HF, yielding 10 eligible trials published between 6/01–3/08. Data was independently extracted and cross-checked for accuracy and reliability (2 investigators). A total of 768 subjects (421 treated and 338 controls) are included (Characteristics in Table 1 ). Randomization to ESA produced a significant improvement in exercise capacity 0.39 standard units [95% CI 0.1– 0.6, p = 0.001], a 5.72% [95% CI 1.2–10.3, p = 0.014] increase in left ventricle ejection fraction and a 0.23 mg/dL [95% CI 0.4 – 0.1 p = 0.001] reduction in serum creatinine. There was no difference in all-cause mortality - RR 0.79 [95% CI 0.49, 1.26, p = 0.320]. Trends were noted in reduced hospitalization rates, decreased brain natriuretic peptide, and improved quality of life. Meta-analysis of randomized studies of treatment of anemia in HF patients suggests significant benefit in exercise capacity, left ventricular ejection fraction, and serum creatinine. There does not appear to be excess mortality with ESA/iron treatment. Despite favorable findings, definitive randomized clinical trials are needed to assess the role of this treatment modality in HF management. Table 1. Baseline Patient and Study Characteristics


Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Peter F Kokkinos ◽  
Puneet Narayan ◽  
Charles Faselis ◽  
Jonathan Myers ◽  
Carl Lavie ◽  
...  

Introduction: Obesity, defined as body mass index (BMI) ≥30 kg/m 2 , is associated with increased incidence of heart failure (HF). Increased cardiorespiratory fitness (CRF), as indicated by increased exercise capacity, is associated with lower risk of cardiovascular disease and HF. However, the CRF-BMI-HF interaction has not been fully explored. Hypothesis: We assessed the hypothesis that the risk of HF associated with increased BMI is moderated by increased CRF. Methods: We identified 19,881 Veterans (mean age: 58.0±11.3 years) who completed an exercise tolerance test (ETT) to assess either CRF status or suspected ischemia at two VA Medical Centers (Washington DC and Palo Alto, CA). None had documented HF at baseline or evidence of ischemia during the ETT. We established four BMI categories: <25 kg/m 2 ; 25-29.9 kg/m 2 ; 30-34.9 kg/m 2 ; and ≥35 kg/m 2 . In addition, we established four CRF categories based on age-stratified quartiles of peak metabolic equivalents (METs) achieved (mean ± SD): Least-Fit (4.5±1.2 METs; n=4,743); Low-Fit (6.6±1.3; n=5,103); Moderate-Fit (8.0±1.3 METs; n=5,084); and High-Fit (11.1±2.4 METs; n=4,951). Multivariable Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals [CI] for incidence of HF across BMI categories for the entire cohort, using BMI 25-29.9 kg/m 2 (lowest HF rate) as the reference group. We then stratified the cohort by the four BMI categories and assessed HF risk across CRF categories within each stratum, using the Least-fit category as the reference group. The models were adjusted for age, race, gender, cardiac risk factors, sleep apnea, alcohol dependence, medications. Results: During follow-up (median=11.8 years), 2,193 developed HF (10.5 per 1,000 person-years of follow-up). The HF risk for normal weight individuals (18.5-24.9 kg/m2) was 10% higher (p=0.93). For obese individuals, the HF risk was 22% higher in those with BMI 30-34.9 kg/m 2 (HR=1.22; 95% CI: 1.09-1.35) and 50% higher (HR=1.50, 95% CI: 1.32-1.72) for those with BMI ≥35 kg/m 2 . When CRF (peak METs achieved) was introduced in the model, the risk for those with BMI 30-34.9 was reduced from 22% to 16% (HR=1.16; 95% CI: 1.04-1.29) and from 50% to 29% (HR=1.29; 95% CI: 1.13-1.48) among those with ≥35 kg/m 2 . For every 1-MET increase in exercise capacity, HF risk was 15% lower (HR=0.85; 95% CI: 0.83-0.87). We then assessed the impact of CRF on the risk of HF within each of the four BMI categories. The HF risk declined progressively (range: 25% to 69%; p<0.01) with increasing fitness within all BMI categories. Conclusions: The obesity-associated increased risk of HF was attenuated by increased CRF. The HF risk was progressively decreased with increased CRF within all BMI categories.


2019 ◽  
Vol 15 (5) ◽  
pp. 377-386 ◽  
Author(s):  
Aaqib H Malik ◽  
Senada S Malik ◽  
Wilbert S Aronow ◽  

Aim: We investigated whether the home-based intervention (HBI) for heart failure (HF), restricted to education and support, improves readmissions or mortality compared with usual care. Patients & methods: We searched PubMed and Embase for randomized controlled trials that examined the impact of HBI in HF. A random-effects meta-analysis was performed using R. Result: Total 17/409 articles (3214 patients) met our inclusion criteria. The pooled estimate showed HBI was associated with a reduction in readmission rates and mortality (22 and 16% respectively; p < 0.05). Subgroup analysis confirmed that the benefit of HBI increases significantly with a longer follow-up. Conclusion: HBI in the form of education and support significantly reduces readmission rates and improves survival of HF patients. HBI should be considered in the discharge planning of HF patients.


BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e029716
Author(s):  
Lea Wildisen ◽  
Elisavet Moutzouri ◽  
Shanthi Beglinger ◽  
Lamprini Syrogiannouli ◽  
Anne R Cappola ◽  
...  

IntroductionProspective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms have yielded conflicting findings, possibly because of differences in age, sex, thyroid-stimulating hormone cut-off levels or degree of baseline depressive symptoms. Analysis of individual participant data (IPD) may help clarify this association.Methods and analysisWe will conduct a systematic review and IPD meta-analysis of prospective studies on the association between subclinical thyroid dysfunction and depressive symptoms. We will identify studies through a systematic search of the literature in the Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to April 2019 and from the Thyroid Studies Collaboration. We will ask corresponding authors of studies that meet our inclusion criteria to collaborate by providing IPD. Our primary outcome will be depressive symptoms at the first available individual follow-up, measured on a validated scale. We will convert all the scores to the Beck Depression Inventory scale. For each cohort, we will estimate the mean difference of depressive symptoms between participants with subclinical hypothyroidism or hyperthyroidism and control adjusted for depressive symptoms at baseline. Furthermore, we will adjust our multivariable linear regression analyses for age, sex, education and income. We will pool the effect estimates of all studies in a random-effects meta-analysis. Heterogeneity will be assessed by I2. Our secondary outcomes will be depressive symptoms at a specific follow-up time, at the last available individual follow-up and incidence of depression at the first, last and at a specific follow-up time. For the binary outcome of incident depression, we will use a logistic regression model.Ethics and disseminationFormal ethical approval is not required as primary data will not be collected. Our findings will have considerable implications for patient care. We will seek to publish this systematic review and IPD meta-analysis in a high-impact clinical journal.PROSPERO registration numberCRD42018091627.


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 ◽  
...  

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.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Indraratna ◽  
D Tardo ◽  
J Yu ◽  
K Delbaere ◽  
M Brodie ◽  
...  

Abstract Introduction Cardiovascular disease (CVD) remains the leading cause of death in the world. Mobile phones have become ubiquitous in most developed societies. Smartphone applications, telemonitoring and clinician-driven short message service (SMS) allow for novel methods in managing chronic cardiovascular conditions such as ischaemic heart disease, heart failure and hypertension. Purpose To evaluate the impact of mobile phone-based interventions (MPIs) on mortality, hospitalisations and blood pressure and body mass index (BMI) in patients diagnosed with either acute coronary syndrome, heart failure or hypertension. Methods A systematic review was conducted using seven electronic databases, identifying all randomised control trials (RCTs) featuring an MPI in the management of these conditions. Meta-analysis was performed by using standard analytical techniques. The odds ratio (OR) was used as a summary statistic. Results Twenty-six RCTs including 6,713 patients were identified. Of these 26 studies, 13 examined text messaging intereventions, 10 studied telemonitoring interventions and three described smartphone applications with other functions. Twelve studies were included for meta-analysis. In patients with heart failure (n=1683), MPIs were associated with a significantly lower rate of all-cause hospital admissions at six months (31% vs. 36%, OR 0.77, 95% CI 0.62–0.97, p=0.03, I2 = 0). A significant difference was also demonstrated for heart-failure admissions (14.0% vs. 18.5%, OR 0.69, 95% CI 0.48 to 0.98, p=0.04, I2 = 26%). There was no difference in mortality (10.4% vs. 11.6% p=0.45). In patients with hypertension, the difference in systolic BP was 4.3mmHg less in the intervention group (95% CI: −7.8 to −0.78 mmHg, p=0.02). Four studies examined medication compliance as an endpoint in patients with ischaemic heart disease, and all four demonstrated a significant difference favouring the MPI group (see table 1). However, due to variable quantification of compliance, meta-analysis was not possible. There was no significant difference in the change in BMI from four studies after six or more months (mean difference −0.46, 95% CI: −1.44 to 0.52, P=0.36). Conclusions The available data suggests MPIs may have a role as valuable adjuncts in the management of chronic CVD. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Health and Medical Research Council (NHMRC)


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