Heart Failure (HF) is a multi-faceted and life-threatening syndrome characterized by significant morbidity and mortality, poor functional capacity and quality of life, and high costs. HF affects more ...than 64 million people worldwide. Therefore, attempts to decrease its social and economic burden have become a major global public health priority. While the incidence of HF has stabilized and seems to be declining in industrialized countries, the prevalence is increasing due to the ageing of the population, improved treatment of and survival with ischaemic heart disease, and the availability of effective evidence-based therapies prolonging life in patients with HF. There are geographical variations in HF epidemiology. There is substantial lack of data from developing countries, where HF exhibits different features compared with that observed in the Western world. In this review, we provide a contemporary overview on the global burden of HF, providing updated estimates on prevalence, incidence, outcomes, and costs worldwide.
Previous systematic reviews and meta-analyses consistently show the positive effect of exercise-based rehabilitation for heart failure (HF) on exercise capacity; however, the direction and magnitude ...of effects on health-related quality of life, mortality and hospital admissions in HF remain less certain. This is an update of a Cochrane systematic review previously published in 2010.
To determine the effectiveness of exercise-based rehabilitation on the mortality, hospitalisation admissions, morbidity and health-related quality of life for people with HF. Review inclusion criteria were extended to consider not only HF due to reduced ejection fraction (HFREF or 'systolic HF') but also HF due to preserved ejection fraction (HFPEF or 'diastolic HF').
We updated searches from the previous Cochrane review. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue1, 2013) from January 2008 to January 2013. We also searched MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO) and PsycINFO (Ovid) (January 2008 to January 2013). We handsearched Web of Science, bibliographies of systematic reviews and trial registers (Controlled-trials.com and Clinicaltrials.gov).
Randomised controlled trials of exercise-based interventions with six months' follow-up or longer compared with a no exercise control that could include usual medical care. The study population comprised adults over 18 years and were broadened to include individuals with HFPEF in addition to HFREF.
Two review authors independently screened all identified references and rejected those that were clearly ineligible. We obtained full-text papers of potentially relevant trials. One review author independently extracted data from the included trials and assessed their risk of bias; a second review author checked data.
We included 33 trials with 4740 people with HF predominantly with HFREF and New York Heart Association classes II and III. This latest update identified a further 14 trials. The overall risk of bias of included trials was moderate. There was no difference in pooled mortality between exercise-based rehabilitation versus no exercise control in trials with up to one-year follow-up (25 trials, 1871 participants: risk ratio (RR) 0.93; 95% confidence interval (CI) 0.69 to 1.27, fixed-effect analysis). However, there was trend towards a reduction in mortality with exercise in trials with more than one year of follow-up (6 trials, 2845 participants: RR 0.88; 95% CI 0.75 to 1.02, fixed-effect analysis). Compared with control, exercise training reduced the rate of overall (15 trials, 1328 participants: RR 0.75; 95% CI 0.62 to 0.92, fixed-effect analysis) and HF specific hospitalisation (12 trials, 1036 participants: RR 0.61; 95% CI 0.46 to 0.80, fixed-effect analysis). Exercise also resulted in a clinically important improvement superior in the Minnesota Living with Heart Failure questionnaire (13 trials, 1270 participants: mean difference: -5.8 points; 95% CI -9.2 to -2.4, random-effects analysis) - a disease specific health-related quality of life measure. However, levels of statistical heterogeneity across studies in this outcome were substantial. Univariate meta-regression analysis showed that these benefits were independent of the participant's age, gender, degree of left ventricular dysfunction, type of cardiac rehabilitation (exercise only vs. comprehensive rehabilitation), mean dose of exercise intervention, length of follow-up, overall risk of bias and trial publication date. Within these included studies, a small body of evidence supported exercise-based rehabilitation for HFPEF (three trials, undefined participant number) and when exclusively delivered in a home-based setting (5 trials, 521 participants). One study reported an additional mean healthcare cost in the training group compared with control of USD3227/person. Two studies indicated exercise-based rehabilitation to be a potentially cost-effective use of resources in terms of gain in quality-adjusted life years (QALYs) and life-years saved.
This updated Cochrane review supports the conclusions of the previous version of this review that, compared with no exercise control, exercise-based rehabilitation does not increase or decrease the risk of all-cause mortality in the short term (up to 12-months' follow-up) but reduces the risk of hospital admissions and confers important improvements in health-related quality of life. This update provides further evidence that exercise training may reduce mortality in the longer term and that the benefits of exercise training on appear to be consistent across participant characteristics including age, gender and HF severity. Further randomised controlled trials are needed to confirm the small body of evidence seen in this review for the benefit of exercise in HFPEF and when exercise rehabilitation is exclusively delivered in a home-based setting.
This article details an updated version of the principles of ethical authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle (JCSM) and its two daughter journals JCSM Rapid ...Communication and JCSM Clinical Reports. We request of all author sending to the journal a paper for consideration that at the time of submission to JCSM, the corresponding author, on behalf of all co‐authors, needs to certify adherence to these principles. The principles are as follows:
all authors listed on a manuscript considered for publication have approved its submission and (if accepted) approve publication in JCSM as provided;
each named author has made a material and independent contribution to the work submitted for publication;
no person who has a right to be recognized as author has been omitted from the list of authors on the submitted manuscript;
the submitted work is original and is neither under consideration elsewhere nor that it has been published previously in whole or in part other than in form;
all authors certify that the submitted work is original and does not contain excessive overlap with prior or contemporaneous publication elsewhere, and where the publication reports on cohorts, trials, or data that have been reported on before the facts need to be acknowledged and these other publications must be referenced;
all original research work has been approved by the relevant bodies such as institutional review boards or ethics committees;
all relevant conflicts of interest, financial or otherwise, that may affect the authors' ability to present data objectively, and relevant sources of funding of the research in question have been duly declared in the manuscript;
the manuscript in its published form will be maintained on the servers of JCSM as a valid publication only as long as all statements in the guidelines on ethical publishing remain true.
If any of the aforementioned statements ceases to be true, the authors have a duty to notify as soon as possible the Editors of JCSM, JCSM Rapid Communication, and JCSM Clinical Reports, respectively, so that the available information regarding the published article can be updated and/or the manuscript can be withdrawn.
Ethical authorship and publishing Coats, Andrew J.S
International journal of cardiology,
01/2009, Volume:
131, Issue:
2
Journal Article
Peer reviewed
Abstract Principles of Ethical Publishing in the International Journal of Cardiology: 1. That the corresponding author has the approval of all other listed authors for the submission and publication ...of all versions of the manuscript. 2. That all people who have a right to be recognised as authors have been included on the list of authors and everyone listed as an author has made an independent material contribution to the manuscript 3. That the work submitted in the manuscript is original and has not been published elsewhere and is not presently under consideration of publication by any other journal. The oral or poster presentation of parts of the work and its publishing as a single page abstract does not count as prior publication for this purpose. 4. That the material in the manuscript has been acquired according to modern ethical standards and does not contain material copied from anyone else without their written permission 5. That all material which derives from prior work, including from the same authors, is properly attributed to the prior publication by proper citation 6. That the manuscript will be maintained on the servers of the Journal and held to be a valid publication by the Journal only as long as all statements in these principles remain true 7. That if any of the statements above ceases to be true the authors have a duty to notify the journal as soon as possible so that the manuscript can be withdrawn.
The relationship between mortality and heart rate remains unclear for patients with heart failure with reduced ejection fraction in either sinus rhythm or atrial fibrillation (AF).
This analysis ...explored the prognostic importance of heart rate in patients with heart failure with reduced ejection fraction in randomized controlled trials comparing beta-blockers and placebo.
The Beta-Blockers in Heart Failure Collaborative Group performed a meta-analysis of harmonized individual patient data from 11 double-blind randomized controlled trials. The primary outcome was all-cause mortality, analyzed with Cox proportional hazard ratios (HR) modeling heart rate measured at baseline and approximately 6 months post-randomization.
A higher heart rate at baseline was associated with greater all-cause mortality for patients in sinus rhythm (n = 14,166; adjusted HR: 1.11 per 10 beats/min; 95% confidence interval CI: 1.07 to 1.15; p < 0.0001) but not in AF (n = 3,034; HR: 1.03 per 10 beats/min; 95% CI: 0.97 to 1.08; p = 0.38). Beta-blockers reduced ventricular rate by 12 beats/min in both sinus rhythm and AF. Mortality was lower for patients in sinus rhythm randomized to beta-blockers (HR: 0.73 vs. placebo; 95% CI: 0.67 to 0.79; p < 0.001), regardless of baseline heart rate (interaction p = 0.35). Beta-blockers had no effect on mortality in patients with AF (HR: 0.96, 95% CI: 0.81 to 1.12; p = 0.58) at any heart rate (interaction p = 0.48). A lower achieved resting heart rate, irrespective of treatment, was associated with better prognosis only for patients in sinus rhythm (HR: 1.16 per 10 beats/min increase, 95% CI: 1.11 to 1.22; p < 0.0001).
Regardless of pre-treatment heart rate, beta-blockers reduce mortality in patients with heart failure with reduced ejection fraction in sinus rhythm. Achieving a lower heart rate is associated with better prognosis, but only for those in sinus rhythm.
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In this pre-specified subanalysis of the SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure) trial, which examined the effects of ...nebivolol in elderly heart failure (HF) patients, we explored the effects of left ventricular ejection fraction (EF) on outcomes, including the subgroups impaired EF (< or =35%) and preserved EF (>35%).
Beta-blockers are established drugs in patients with HF and impaired EF, but their value in preserved EF is unclear.
We studied 2,111 patients; 1,359 (64%) had impaired (< or =35%) EF (mean 28.7%) and 752 (36%) had preserved (>35%) EF (mean 49.2%). The effect of nebivolol was investigated in these 2 groups, and it was compared to explore the interaction of EF with outcome. Follow-up was 21 months; the primary end point was all-cause mortality or cardiovascular hospitalizations.
Patients with preserved EF were more often women (49.9% vs. 29.8%) and had less advanced HF, more hypertension, and fewer prior myocardial infarctions (all p < 0.001). During follow-up, the primary end point occurred in 465 patients (34.2%) with impaired EF and in 235 patients (31.2%) with preserved EF. The effect of nebivolol on the primary end point (hazard ratio HR of nebivolol vs. placebo) was 0.86 (95% confidence interval: 0.72 to 1.04) in patients with impaired EF and 0.81 (95% confidence interval: 0.63 to 1.04) in preserved EF (p = 0.720 for subgroup interaction). Effects on all secondary end points were similar between groups (HR for all-cause mortality 0.84 and 0.91, respectively), and no p value for interaction was <0.48.
The effect of beta-blockade with nebivolol in elderly patients with HF in this study was similar in those with preserved and impaired EF.
The Journal of Cachexia, Sarcopenia and Muscle (JCSM) aims to publish articles with relevance to wasting disorders and illnesses of the muscle in the broadest sense. In order to avoid publication of ...inappropriate articles and to avoid protracted disputes, the Editors have established ethical guidelines that detail a number of regulations to be fulfilled prior to submission to the journal. This article updates the principles of ethical authorship and publishing in JCSM and its two daughter journals JCSM Rapid Communication and JCSM Clinical Reports. We require the corresponding author, on behalf of all co‐authors, to certify adherence to the following principles:
All authors listed on a manuscript considered for publication have approved its submission and (if accepted) approve publication in the journal;
Each named author has made a material and independent contribution to the work submitted for publication;
No person who has a right to be recognized as author has been omitted from the list of authors on the submitted manuscript;
The submitted work is original and is neither under consideration elsewhere nor that it has been published previously in whole or in part other than in form;
All authors certify that the submitted work is original and does not contain excessive overlap with prior or contemporaneous publication elsewhere, and where the publication reports on cohorts, trials, or data that have been reported on before the facts need to be acknowledged and these other publications must be referenced;
All original research work has been approved by the relevant bodies such as institutional review boards or ethics committees;
All relevant conflicts of interest, financial or otherwise, that may affect the authors' ability to present data objectively, and relevant sources of funding of the research in question have been duly declared in the manuscript;
All authors certify that they will submit the original source data to the editorial office upon request;
The manuscript in its published form will be maintained on the servers of the journal as a valid publication only as long as all statements in these guidelines remain true;
If any of the aforementioned statements ceases to be true, the authors have a duty to notify as soon as possible the Editor‐in‐Chief of the journal, so that the available information regarding the published article can be updated and/or the manuscript can be withdrawn.
Abstract
Aims
Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40–49% should be managed similar to LVEF ≥ 50%. We investigated the effect of ...beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials.
Methods and results
Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21–33%), including 575 patients with LVEF 40–49% and 244 ≥ 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF ≥ 50%. For LVEF 40–49%, death occurred in 21/292 7.2% randomized to beta-blockers compared to 35/283 12.4% with placebo; adjusted hazard ratio (HR) 0.59 95% confidence interval (CI) 0.34–1.03. Cardiovascular death occurred in 13/292 4.5% with beta-blockers and 26/283 9.2% with placebo; adjusted HR 0.48 (95% CI 0.24–0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF ≥50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis.
Conclusion
Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40–49%.
Background
Chronic heart failure (HF) is a growing global health challenge. People with HF experience substantial burden that includes low exercise tolerance, poor health‐related quality of life ...(HRQoL), increased risk of mortality and hospital admission, and high healthcare costs. The previous (2014) Cochrane systematic review reported that exercise‐based cardiac rehabilitation (CR) compared to no exercise control shows improvement in HRQoL and hospital admission among people with HF, as well as possible reduction in mortality over the longer term, and that these reductions appear to be consistent across patient and programme characteristics. Limitations noted by the authors of this previous Cochrane Review include the following: (1) most trials were undertaken in patients with HF with reduced (< 45%) ejection fraction (HFrEF), and women, older people, and those with preserved (≥ 45%) ejection fraction HF (HFpEF) were under‐represented; and (2) most trials were undertaken in the hospital/centre‐based setting.
Objectives
To determine the effects of exercise‐based cardiac rehabilitation on mortality, hospital admission, and health‐related quality of life of people with heart failure.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and three other databases on 29 January 2018. We also checked the bibliographies of systematic reviews and two trial registers.
Selection criteria
We included randomised controlled trials that compared exercise‐based CR interventions with six months' or longer follow‐up versus a no exercise control that could include usual medical care. The study population comprised adults (> 18 years) with evidence of HF ‐ either HFrEF or HFpEF.
Data collection and analysis
Two review authors independently screened all identified references and rejected those that were clearly ineligible for inclusion in the review. We obtained full papers of potentially relevant trials. Two review authors independently extracted data from the included trials, assessed their risk of bias, and performed GRADE analyses.
Main results
We included 44 trials (5783 participants with HF) with a median of six months' follow‐up. For this latest update, we identified 11 new trials (N = 1040), in addition to the previously identified 33 trials. Although the evidence base includes predominantly patients with HFrEF with New York Heart Association classes II and III receiving centre‐based exercise‐based CR programmes, a growing body of studies include patients with HFpEF and are undertaken in a home‐based setting. All included studies included a no formal exercise training intervention comparator. However, a wide range of comparators were seen across studies that included active intervention (i.e. education, psychological intervention) or usual medical care alone. The overall risk of bias of included trials was low or unclear, and we downgraded results using the GRADE tool for all but one outcome.
Cardiac rehabilitation may make little or no difference in all‐cause mortality over the short term (≤ one year of follow‐up) (27 trials, 28 comparisons (2596 participants): intervention 67/1302 (5.1%) vs control 75/1294 (5.8%); risk ratio (RR) 0.89, 95% confidence interval (CI) 0.66 to 1.21; low‐quality GRADE evidence) but may improve all‐cause mortality in the long term (> 12 months follow up) (6 trials/comparisons (2845 participants): intervention 244/1418 (17.2%) vs control 280/1427 (19.6%) events): RR 0.88, 95% CI 0.75 to 1.02; high‐quality evidence). Researchers provided no data on deaths due to HF. CR probably reduces overall hospital admissions in the short term (up to one year of follow‐up) (21 trials, 21 comparisons (2182 participants): (intervention 180/1093 (16.5%) vs control 258/1089 (23.7%); RR 0.70, 95% CI 0.60 to 0.83; moderate‐quality evidence, number needed to treat: 14) and may reduce HF‐specific hospitalisation (14 trials, 15 comparisons (1114 participants): (intervention 40/562 (7.1%) vs control 61/552 (11.1%) RR 0.59, 95% CI 0.42 to 0.84; low‐quality evidence, number needed to treat: 25). After CR, a clinically important improvement in short‐term disease‐specific health‐related quality of life may be evident (Minnesota Living With Heart Failure questionnaire ‐ 17 trials, 18 comparisons (1995 participants): mean difference (MD) ‐7.11 points, 95% CI ‐10.49 to ‐3.73; low‐quality evidence). Pooling across all studies, regardless of the HRQoL measure used, shows there may be clinically important improvement with exercise (26 trials, 29 comparisons (3833 participants); standardised mean difference (SMD) ‐0.60, 95% CI ‐0.82 to ‐0.39; I² = 87%; Chi² = 215.03; low‐quality evidence). ExCR effects appeared to be consistent different models of ExCR delivery: centre vs. home‐based, exercise dose, exercise only vs. comprehensive programmes, and aerobic training alone vs aerobic plus resistance programmes.
Authors' conclusions
This updated Cochrane Review provides additional randomised evidence (11 trials) to support the conclusions of the previous version (2014) of this Cochane Review. Compared to no exercise control, CR appears to have no impact on mortality in the short term (< 12 months' follow‐up). Low‐ to moderate‐quality evidence shows that CR probably reduces the risk of all‐cause hospital admissions and may reduce HF‐specific hospital admissions in the short term (up to 12 months). CR may confer a clinically important improvement in health‐related quality of life, although we remain uncertain about this because the evidence is of low quality. Future ExCR trials need to continue to consider the recruitment of traditionally less represented HF patient groups including older, female, and HFpEF patients, and alternative CR delivery settings including home‐ and using technology‐based programmes.
Aims
Use and dosing of guideline‐directed medical therapy (GDMT) in patients with heart failure (HF) have been shown to be suboptimal. Among new users of GDMT in HF, we followed the real‐life ...patterns of dose titration and discontinuation of angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), beta‐blockers, mineralocorticoid receptor antagonists (MRA) and angiotensin receptor–neprilysin inhibitors (ARNI).
Methods and results
New users were identified in health care databases in Sweden, UK and US between 2016–2019. Inclusion criterion was a recent HF hospitalization (HHF) triggering the initiation of GDMT. Patients were grouped by GDMT, i.e. ACEi, ARB, beta‐blocker, MRA and ARNI, and stratified by initial dose. Follow‐up was 12 months, until death or study end. Outcomes were dose titration within each drug class, discontinuation and first HHF or death. Dose/discontinuation follow‐up was assessed daily based on the coverage length of a filled prescription and reported on day 365. New users of ACEi (n = 8426), ARB (n = 2303), beta‐blockers (n = 10 476), MRA (n = 17 421), and ARNI (n = 29 546) were identified. Over 12 months, target dose achievement was 15%, 10%, 12%, 30%, and discontinuation was 55%, 33%, 24% and 27% for ACEi, ARB, beta‐blockers and ARNI, respectively. MRA was rarely titrated and discontinuation rates were high (40%). Event rates for HHF or death ranged from 40.0–86.9 per 100 patient‐years across the treatment groups.
Conclusion
Despite high risk of clinical events following HHF, new initiation of GDMT was followed by consistent patterns of low up‐titration and early GDMT discontinuation in three countries with different health care and economies. Our data highlight the urgent need for moving away from long sequential approach when initiating HF treatment and for improving just‐in‐time decision support for patients and health care providers.
New users were identified in health care databases in Sweden, UK and US between 2016–2019. Inclusion criterion was a recent HHF triggering the initiation of GDMT. Patients were grouped by GDMT, i.e. ACEi, ARB, beta‐blocker, MRA and ARNI, and stratified by initial dose. Follow‐up was 12 months, until death or end of the registry. Outcomes were dose titration within each drug class, discontinuation and first HHF or all‐cause death. Dose/discontinuation follow‐up was assessed daily based on the coverage length of a filled prescription and reported on day 365. Due to the different structure of the registries used for the current analysis, the time‐windows adopted for identifying previous use of the drug differed across the three countries. In particular, in UK and Sweden the filled prescriptions for the treatments were checked since 2013 and 2014, respectively, i.e. wash‐out of 3 and 2 years, respectively, whereas in the US it was limited to 6 months. The 1‐year longer wash‐out in UK vs. Sweden was due to the fact that UK patients living in rural areas often receive prescriptions once/twice yearly covering the entire year rather than monthly, and therefore a longer wash‐out period was deemed necessary. Even shorter wash‐out in the US was due to the frequent changes in healthcare insurance providers, which would have led to a limited number of patients with data available 2 or 3 years prior to HHF. Furthermore, recent HHF was defined as 7 days prior to the initiation of GDMT in Sweden and US, but prior to 30 days in UK where patients are typically provided with 1‐month drug supply at discharge.