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Research Article: Study Protocol Systematic Review

Different exercise therapies for treating heart failure

A protocol for overview of systematic reviews and network meta-analysis

Zhang, Li MNa,b; Zhao, Xiao-Peng MDa; Qiao, Li-juan MNc; Wei, Wan-xia MNa; Wei, Min MNa; Ding, Jin MNa,∗; Li, Ying-dong MD, PhDd,∗

Author Information
doi: 10.1097/MD.0000000000022710
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1 Introduction

Heart failure (HF) is a complex clinical syndrome caused by impaired ventricular structure or function resulting in fullness and ejection dysfunction, It‘s clinical manifestations include dyspnea, fatigue, and fluid retention, the first of which leads to limited mobility, and the second leads to congestion of the lungs and/or internal organs and/or peripheral edema,[1] which severely affects the patient's quality of life. It is estimated that the current prevalence of HF in the world is 38 million, the prevalence of HF in adults in Europe is 1% to 2%, and in China it has increased to 2% to 3%. The mortality and rehospitalization rates are also high.[2–5]

The treatment goal of Chronic Heart Failure (CHF) is to improve cardiac function and eliminate symptoms, improve quality of life and survival. Although clinical drug therapies under the guidance of the latest guidelines can alleviate the clinical symptoms and improve the survival rate of patients with HF, it still needs to be combined with non-drug management for better intervention effect.[6] Exercise rehabilitation plays an increasingly important role in the non-drug management of HF. It has been proved to be safe and effective and can improve patients’ cardiac function, increase their exercise endurance and improve their quality of life, which has been recommended by various guidelines.[6–8]

Systematic review (SR) is a high-level evidence type, which is one of the important basis for clinical decision-making, and has important reference value in the development of clinical practice guideline.[9,10] It can also provide information on the level of healthcare management and policy making by providing research-based answers to important questions about health systems.[11] Overview of SR is a comprehensive research method to comprehensively collect the relevant SR of the treatment and diagnosis of the same disease or the same health problem for overview, which can provide more concentrated and high-quality evidence for the users of evidence.[12] It has also important reference value for the formulation of clinical guidelines, but poor quality SR can also mislead decision makers.[13] In recent years, many clinical trials, SR and meta-analysis have proved the advantages of exercise therapies in HF. However, due to the limitations of methodological quality and reporting quality of individual studies, the level of evidence will be affected to some extent. And because of the variety of exercises involved, whether exercise therapies can be used as a complementary alternative to HF for clinicians, and which exercise should be selected first in clinical practice, lack of high-quality evidence support, and there is no uniform standard. Finally, the effectiveness and safety of clinical interventions will be affected.

Therefore, this study intends to overview of SRs and network meta-analysis of exercise therapies intervention in HF. The Assessment of Multiple Systematic Reviews-2 (AMSTAR2) scale[14–18] will use to evaluate the methodological quality of the included literature. The (PRISMA) statement[19,20] will use to evaluate the report quality of the literature. The GRADE system[21,22] will use to evaluate the quality of evidence for the results of the included studies. In addition, Network Meta-analysis will use to rank the effects of exercise therapies on HF, so as to provide some references for clinical decision-making.

2 Methods

2.1 Study registration

This protocol has been registered at INPLASY202080118. This study will follow the guidelines of the Preferred Reporting Items for SR and Meta-Analysis Protocol statement.[23,24]

2.2 Data sources and search strategy

This study will search the following databases: PubMed, Web of Science, Cochrane Library, EMBASE, Chinese biomedical literature database (CBM), China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), and Wan Fang database. Related words will be searched by medical subject headings (Mesh) or text word search. The retrieval strategy will be designed for each database. The language is limited to English and Chinese, and there are no other restrictions. The search strategy of PubMed and EMBASE are shown in Tables 1 and 2. When the screening is completed, check the references list of included SR and meta-analysis to determine whether other SR and meta-analysis can be included.

Table 1
Table 1:
A draft search strategy using PubMed.
Table 2
Table 2:
A draft search strategy using Embase.

2.3 Eligibility criteria for study selection

2.3.1 Types of study

This study will include SR or meta-analysis in which exercise therapies was used for the treatment of patients with HF. The SR must be in English or Chinese, and up to standard of the following subjects, interventions, and outcome indicators.

2.3.2 Types of participants

According to World Health Organization[25] and “Guidelines for the Diagnosis and Treatment of Heart Failure in China,”[26] this study will include participants who were diagnosed as HF, irrespective sex, age, and duration.

2.3.3 Types of interventions

All exercise therapies interventions for HF are included, such as Aerobic exercise, inspiratory muscle training (IMT), Qigong, Tai Chi, Dance, Yoga, and so on.

2.3.4 Types of outcome measures

The primary outcomes were peak oxygen uptake, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), ventilation over carbon dioxide slope, oxygen uptake efficiency slope, exercise oscillatory ventilation, rest and peak pulmonary end-tidal CO2. The secondary outcomes were blood pressure, heart rate, 6-minute walk test (6MWT), brain natriuretic peptide (BNP), and quality of life (QoL).

2.3.5 Exclusion criteria

  • 1. Literatures published repeatedly by the same author or with duplicate data;
  • 2. The quality evaluation of SR or methodological research literatures;
  • 3. Non-Chinese and English literatures;
  • 4. The full text of the literature is not available.

2.4 Data collection and analysis

2.4.1 Selection of studies

Two independent reviewers (LZ and LJQ) will check titles/abstracts of all potential literatures, and will remove irrelevant studies. We will read full-text of potential trials to determine if they fulfill all inclusion criteria. Excluded studies will be listed with specific reasons in a table. Any divergences will be solved by consulting a third reviewer (WXW). The procedure of study selection is demonstrated in a flow chart (Fig. 1).

Figure 1
Figure 1:
The flowchart of the screening process.

2.4.2 Data extraction and management

Two researchers (MW and WXW) applied EndNote X 8.0 (Thomson Reuters (Scientific) LLC Philadelphia, PA) Software manages literature. The pre-designed Microsoft Excel 2019 software table will be used to extract the following information: author, year of publication, number of references, number of cases, interventions, control measures, method quality assessment tool, safety assessment, and risk of bias.

2.4.3 Quality appraisal

The AMSTAR-2 measurement tool was used for methodological evaluation, it uses items 2, 4, 7, 9, 11, 13, and 15 as key items affecting the SR production and the validity of its results, and the remaining items as non-key items.[27] If ≤1 non-critical item is not satisfied, it will be evaluated as “high” quality level. If >1 non-key items is not sufficient, the price is rated as “medium” quality level; if a key item is not satisfied, with or without a non-key item, the quality level is “low” level. If >1 key item is not satisfied, with or without non-key item, it will be evaluated as “very low” quality level.[28]

The (PRISMA) statement was used for reporting quality evaluation,[27] it consists of 27 items. The scoring principle is 1 point for complete report, 0.5 point for partial report and 0 point for non-report. The full score is 27 points, if ≤15 means relatively serious information defect, 15 to 21 means certain defect, 21 to 27 means relatively complete report.

The GRADE tool was used to grade the evidence quality of the major outcome indicators. In the GRADE evaluation,[22] there was no evidence of downgrade as high quality, 1 item is downgraded to medium quality, 2 items are downgraded to low quality, and 3 items or more are downgraded to very low quality.

2.5 Data synthesis

First, pairwise direct comparisons will be performed, and then network meta-analysis will use to analyze the two-arm studies in which the three-arm studies will divide into pairwise comparisons. For dichotomous variables, odds ratios (ODD Radio, OR) and 95% confidence intervals (CI) will be used to evaluate the effectiveness of different exercise therapies in improving HF. For continuous variables, they will be expressed as standard mean difference (SMD) and 95%CI. The heterogeneity of pairwise comparison will be determined by I2 and P-values. If I2 ≤50% and P ≥ .05, there was no significant heterogeneity in the included study. Significant heterogeneity will be indicated when I2 > 50% or P < .05.[29]

We will use the random effect model of Stata.15.0 to conduct paired meta-analysis of direct evidence. By comparing direct and indirect estimates and calculating inconsistencies within each evidence closed-loop, differences between direct and indirect evidence for the same comparison are explored.[30] The node-splitting method is used to evaluate whether there is inconsistency in all existing comparative analysis, that is, whether there is inconsistency in direct and indirect evidence.[31] For the comparison of the effectiveness of intervention measures, the therapeutic effect of intervention measures was ranked by using the surface area under the cumulative curve and the average level as evaluation indexes. The larger the surface area under the cumulative curve and the smaller the average level were, the better the therapeutic effect of intervention measures would be.[32] Comparative corrected funnel plots are used to detect potential small sample effects or publication bias.[33]

2.6 Subgroup analysis

If possible, we will do some extra subgroup analyses according to the results of heterogeneity and inconsistency (such as age, intensity of exercise). We will also investigate the sources of heterogeneity to determine the robustness and reliability of the consolidated results.

3 Results

3.1 Results of selected studies

Three thousand one hundred and thirty-seven references were initially detected, and 658 duplicates were excluded. After reading the titles and abstracts, 2411 articles were excluded that the type of research and intervention measures were not consistent with the theme. By further reading the full text, 53 references were excluded including exercise mode unclear, other cardiovascular diseases and other cardiac rehabilitation methods. Finally, 33 literatures were included for analysis. The screening details are shown in Figure 1.

3.2 Interventions of included studies

Among the literatures that met the requirements, the studies on the intervention of exercise therapies for HF were as follows: 14 Traditional Chinese Exercise, 12 aerobic exercise, 4 IMT, 1 yoga and 2 dance therapies.

4 Discussion

The current data suggest that the effectiveness of exercise therapies in cardiac rehabilitation of patients with HF has been established, but further research is needed to determine the optimal exercise pattern, exercise duration, exercise combination, and the HF population that will benefit the most. The results of our review will provide a comprehensive description on reporting and methodological quality of existing SRs/MAs and effects of exercises therapies for HF.

Author contributions

Li Zhang, Xiao-Peng Zhao, and Ying-Dong Li conceived the study, developed the criteria. Li Zhang, Wan-Xia Wei, Li-Juan Qiao, Min Wei Searched the literature, In charge of extracting data, and verification. Li Zhang and Wan-Xia Wei analyzed the data. Li Zhang and Jin Ding wrote the protocol and revised the manuscript. Xiao-Peng Zhao provided expertise on treatments, outcomes and related knowledge. Ying-Dong Li checked all work of the review. All authors have read and approved the final manuscript.

Conceptualization: Li Zhang, Xiao peng Zhao, Jin Ding.

Data curation: Li Zhang, Li juan Qiao, Wan xia Wei, Min Wei.

Formal analysis: Li Zhang, Li juan Qiao, Wan xia Wei.

Investigation: Xiao peng Zhao, Li juan Qiao, Min Wei.

Methodology: Xiao peng Zhao, Jin Ding.

Project administration: Ying dong Li.

Supervision: Ying dong Li.

Writing – original draft: Li Zhang.

Writing – review & editing: Jin Ding.


[1]. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013;128:1810–52.
[2]. Ziaeian B, Fonarow GC. Epidemiology and aetiology of heart failure. Nat Rev Cardiol 2016;13:368–78.
[3]. Huang J. Epidemiological characteristics and prevention strategies of heart failure in China. Chin J Heart Heart Rhythm (Electronic Edition) 2015;3:2–3.
[4]. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Kardiol Pol 2016;74:1037–147.
[5]. Braunwald E. The war against heart failure: the Lancet lecture. Lancet 2015;385:812–24.
[6]. Yang J, Zhang J, Han Y. Chinese guidelines for the diagnosis and treatment of heart failure 2018. Chin J Heart Fail Cardiomyopathy 2018;2018:196–225.
[7]. Atherton JJ, Sindone A, De Pasquale CG, et al. National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: guidelines for the prevention, detection, and management of heart failure in Australia. Heart Lung Circ 2018;27:1123–208.
[8]. Ezekowitz JA, O’Meara E, McDonald MA, et al. 2017 comprehensive update of the Canadian Cardiovascular Society guidelines for the management of heart failure. Can J Cardiol 2017;33:1342–433.
[9]. Norris SL, Meerpohl JJ, Akl EA, et al. The skills and experience of GRADE methodologists can be assessed with a simple tool. J Clin Epidemiol 2016;79:150–8.
[10]. Wang X, Chen Y, Yao L, et al. Reporting of declarations and conflicts of interest in WHO guidelines can be further improved. J Clin Epidemiol 2018;98:1–8.
[11]. Li X-X, Zheng Y, Chen Y-l, et al. The reporting characteristics and methodological quality of Cochrane reviews about health policy research. Health Pol 2015;119:503–10.
[12]. Yang K, Liu Y, Yuan J, et al. An Overview of Systematic reviews in development and improvement. Chin J Evid Based Pediatr 2011;6:54–7.
[13]. Xiong J, Chen R, Li W. Review/Meta analysis of acupuncture in the treatment of cervical spondylosis based on radar plot. Chin J Tradit Chin Med Pharm 2012;27:1064–8.
[14]. Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ 2017;358:j4008.
[15]. Ge L, Pan B, Pan J, et al. An Introduction of AMSTAR-2: a quality assessment Instrument of systematic reviews including randomized or non-randomized controlled trial or both. Chin J Drug Eval 2017;34:334–8.
[16]. Tao H, Yang L, Ping A, et al. Interpretation of AMSTAR 2: a critical appraisal tool for systematic reviews that include randomized or non-randomized studies of healthcare interventions. Chin J Evid Based Med 2018;18:101–8.
[17]. Zhang F, Shen A, Zeng X, et al. An Introduction to AMSTAR 2: a critical appraisal tool for systematic reviews. Chin J Evid Based Cardio Med 2018;10:14–8.
[18]. Ni P, Shi J. Update and prospect of system review and meta-analysis revaluation. Chin J Evid Based Cardio Med 2018;10:1170–4.
[19]. Tian J, Ge L, Zhao Y, et al. An introduction to PRISMA extension statement for network meta-analysis. Chin J Drug Eval 2015;32:266–72.
[20]. Moher D, Liberati A, Tetzlaff J, et al. Reprint—preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Phys Ther 2009;89:873–80.
[21]. Atkins D, Best D, Briss PA, et al. Grading quality of evidence and strength of recommendations. BMJ 2004;328:1490.
[22]. Zeng X, Leng W, Li S, et al. How to understand and use GRADE system correctly a briefly outline. Chin J Evid Based Med 2011;11:985–90.
[23]. Shamseer L, Moher D, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2015;350:g7647.
[24]. Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015;4:1.
[25]. Nomenclature, Criteria for Diagnosis of Ischemic Heart Disease. Report of the Joint International Society and Federation of Cardiology/World Health Organization task force on standardization of clinical nomenclature. Circulation 1979;59:607–9.
[26]. 2018 Chinese Guidelines for Prevention and Treatment of Hypertension—A report of the Revision Committee of Chinese Guidelines for Prevention and Treatment of Hypertension. J Geriatr Cardiol. 2019;16:182–241.
[27]. Zhang X, Hu Y, Zhang X, et al. An overview of systematic reviews on Tuina from 2013 to 2017. Chin J Evid Based Med 2019;19:361–7.
[28]. Luo L, Li J, Yang H, et al. Acupuncture for Facioplegia: an overview of systematic reviews. Liao Ning J Tradit Chin Med 2019;46:467–72.
[29]. Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–60.
[30]. Bucher HC, Guyatt GH, Griffith LE, et al. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997;50:683–91.
[31]. Higgins JP, Jackson D, Barrett JK, et al. Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies. Res Synth Method 2012;3:98–110.
[32]. Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol 2011;64:163–71.
[33]. van Valkenhoef G, Dias S, Ades AE, et al. Automated generation of node-splitting models for assessment of inconsistency in network meta-analysis. Res Synth Methods 2016;7:80–93.

exercise therapy; heart failure; meta-analysis; systematic review

Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.