Aerobic exercise effect on prognostic markers for systolic heart failure patients: a systematic review and meta-analysis

Abstract

From previous systematic reviews and meta-analyses, there is consensus about the positive effect of exercise training on exercise capacity for systolic heart failure (HF); however, the effect on actual prognostic markers such as NTproBNP and minute ventilation/carbon dioxide production (VE/VCO₂) slope has not been evaluated. The primary aim of the proposed study is to determine the effect of aerobic exercise training (AEX) on the VE/VCO₂ slope and NTproBNP. The following databases (up to February 30, 2013) were searched with no language limitations: CENTRAL (The Cochrane Library 2013, issue 2), MEDLINE (from January 1966), EMBASE (from January 1980), and Physiotherapy Evidence Database (PEDro) (from January 1929). We screened reference lists of articles and also conducted an extensive hand search of the literature. Randomized controlled trials of exercise-based interventions with 2-month follow-up or longer compared to usual medical care or placebo were included. The study population comprised adults aged between 18 and 65 years, with evidence of chronic systolic heart failure (LVEF < 45 % and baseline NTproBNP > 300 pg/ml). Two review authors independently extracted data on study design, participants, interventions, and outcomes. We assessed the risk of bias using PEDro scale. We calculated mean differences (MD) or standardized mean differences between intervention and control groups for outcomes with sufficient data; for other outcomes, we described findings from individual studies. Eight studies involving a total of 408 participants met the inclusion criteria across the NTproBNP (5 studies with 191 patients) and VE/VCO₂ slope (4 studies with 217 patients). Aerobic exercise significantly improved NTproBNP by a MD of −817.75 [95 % confidence interval (CI) −929.31 to −706.19]. Mean differences across VE/VCO₂ slope were −6.55 (95 % CI −7.24 to −5.87). Those patients’ characteristics and exercise were similar (frequency = 3–5 times/week; duration = 20–50 min/day; intensity = 60–80 % of VO₂ peak) on the included studies. Moreover, the risk of bias across all studies was homogeneous (PEDro scale = 7–8 points). However, based on the statistical analysis, the heterogeneity among the studies was still high, which is related to the variable characteristics of the studies. Aerobic exercise may be effective at improving NTproBNP and the VE/VCO₂ slope in systolic HF patients, but these effects are limited to a specific HF population meeting specific inclusion criterion in a limited number of studies. Future randomized controlled studies including diastolic and HF overleap with pulmonary diseases are needed to better understand the exact influence of AEX.

Appendix 1: Comprehensive search strategy

Search terms strategy for outcome 1: VE/VCO₂ slope (Mesh and Entry Terms)

(Exercise [Mesh] OR Exercises OR “Exercise, Physical” OR “Exercises, Physical” OR “Physical Exercise” OR “Physical Exercises” OR “Exercise, Aerobic” OR “Aerobic Exercises” OR “Exercises, Aerobic” OR “Aerobic Exercise” OR “Exercise Therapy” [Mesh] OR “Therapy, Exercise” OR “Exercise Therapies” OR “Therapies, Exercise” OR “Physical Education and Training” [Mesh] OR “Physical Education, Training” OR “Physical Education” OR “Education, Physical” OR “Physical and Rehabilitation Medicine” [Mesh] OR “Medicine, Physical” OR “Physical Medicine” OR “Physiatry” OR “Physical Medicine and Rehabilitation” OR “Physiatrics”) AND (“Exercise Test” [Mesh] OR “Exercise Tests” OR “Test, Exercise” OR “Tests, Exercise” OR “Bicycle Ergometry Test” OR “Bicycle Ergometry Tests” OR “Ergometer Test, Bicycle” OR “Ergometry Tests, Bicycle” OR “Test, Bicycle Ergometry” OR “Tests, Bicycle Ergometry” OR “Treadmill Test” OR “Test, Treadmill” OR “Tests, Treadmill” OR “Treadmill Tests” OR “Step Test” OR “Step Tests” OR “Test, Step” OR “Tests, Step” OR “Stress Test” OR “Arm Ergometry Test” OR “Arm Ergometry Tests” OR “Ergometry Test, Arm” OR “Ergometry Tests, Arm” OR “Test, Arm Ergometry” OR “Tests, Arm Ergometry” OR “Cardiopulmonary Exercise Test” OR “Cardiopulmonary Exercise Tests” OR “Exercise Test, Cardiopulmonary” OR “Exercise Tests, Cardiopulmonary” OR “Test, Cardiopulmonary Exercise” OR “Tests, Cardiopulmonary Exercise” OR “Oxygen Consumption” [Mesh] OR “Consumption, Oxygen” OR “Consumptions, Oxygen” OR “Oxygen Consumptions” OR “Exercise Tolerance” [Mesh] OR “Tolerance, Exercise” OR “Physical Fitness” [Mesh] OR “Fitness, Physical” OR “Physical Conditioning, Human” OR “Conditioning, Human Physical” OR “Conditionings, Human Physical” OR “Human Physical Conditioning” OR “Human Physical Conditionings” OR “Physical Conditionings, Human” OR “Physical Exertion” [Mesh] OR “Exertion, Physical” OR “Exertions, Physical” OR “Physical Exertions” OR “Physical Effort” OR “Effort, Physical” OR “Efforts, Physical” OR “Physical Efforts” OR “Physical Endurance” [Mesh] OR “Endurance, Physical” OR “Endurances, Physical” OR “Physical Endurances” OR “Blood Gas Monitoring, Transcutaneous” [Mesh] OR “Transcutaneous Blood Gas Monitoring” OR “Cutaneous Oximetry” OR “Cutaneous Oximetries” OR “Oximetries, Cutaneous” OR “Oximetry, Cutaneous” OR “Oximetry, Transcutaneous” OR “Oximetries, Transcutaneous” OR “Transcutaneous Oximetries” OR “Transcutaneous Oximetry” OR “Oxygen Partial Pressure Determination, Transcutaneous” OR “Transcutaneous Capnometry” OR “Capnometries, Transcutaneous” OR “Capnometry, Transcutaneous” OR “Transcutaneous Capnometries” OR “Carbon Dioxide Partial Pressure Determination, Transcutaneous” OR PtcO2 OR TcPCO2 OR “Carbon Dioxide” [Mesh] OR “Dioxide, Carbon” OR “Carbonic Anhydride” OR “Anhydride, Carbonic” OR Capnography [Mesh] OR Capnographies OR “Respiratory Insufficiency” [Mesh] OR “Respiratory Failure” OR “Respiratory Depression” OR “Ventilatory Depression” OR “Depressions, Ventilatory”).

Search terms strategy for outcome 2: NTproBNP (Mesh and Entry Terms)

(Exercise [Mesh] OR Exercises OR “Exercise, Physical” OR “Exercises, Physical” OR “Physical Exercise” OR “Physical Exercises” OR “Exercise, Aerobic” OR “Aerobic Exercises” OR “Exercises, Aerobic” OR “Aerobic Exercise” OR “Exercise Therapy” [Mesh] OR “Therapy, Exercise” OR “Exercise Therapies” OR “Therapies, Exercise” OR “Physical Education and Training” [Mesh] OR “Physical Education, Training” OR “Physical Education” OR “Education, Physical” OR “Physical and Rehabilitation Medicine” [Mesh] OR “Medicine, Physical” OR “Physical Medicine” OR “Physiatry” OR “Physical Medicine and Rehabilitation” OR “Physiatrics”) AND (“Natriuretic Peptide, Brain” [Mesh] OR “Peptide, Brain Natriuretic” OR “Brain Natriuretic Peptide” OR “BNP-32” OR “BNP 32” OR Nesiritide OR “B-Type Natriuretic Peptide” OR “Natriuretic Peptide, B-Type” OR “BNP Gene Product” OR “Type-B Natriuretic Peptide” OR “Natriuretic Peptide, Type-B” OR “Type B Natriuretic Peptide” OR “Natriuretic Peptide Type-B” OR “Natriuretic Peptide Type B” OR “Natriuretic Factor-32” OR “Natriuretic Factor 32” OR “Brain Natriuretic Peptide-32” OR “Brain Natriuretic Peptide 32” OR “Natriuretic Peptide-32, Brain” OR “Peptide-32, Brain Natriuretic” OR “Ventricular Natriuretic Peptide, B-type” OR “Ventricular Natriuretic Peptide, B type” OR Natrecor OR “Atrial Natriuretic Factor” [Mesh] OR Auriculin OR ANP OR “Natriuretic Peptides, Atrial” OR ANF OR Atriopeptins OR “Atrial Natriuretic Peptides” OR “Peptides, Atrial Natriuretic” OR “beta-Atrial Natriuretic Peptide” OR “beta Atrial Natriuretic Peptide” OR “beta-ANP” OR “beta ANP” OR “alpha-ANP Dimer” OR “alpha ANP Dimer” OR “alpha-Atrial Natriuretic Peptide” OR “alpha Atrial Natriuretic Peptide” OR “ANP-(99–126)” OR “Atriopeptin (99–126)” OR “Cardionatrin I” OR “Atrial Natriuretic Factor (99–126)” OR “ANF (1–28)” OR “Atriopeptin (1–28)” OR “Atrial Natriuretic Factor (1–28)” OR “gamma ANP (99–126)” OR “alpha ANP” OR “Cardiodilatin (99–126)” OR “ANP Prohormone (99–126)” OR “ANF (99–126)” OR “ANP (1–28)” OR “Atrial Natriuretic Factor Precursors” OR “Prepro-Cardiodilatin-Atrial Natriuretic Factor” OR “Prepro Cardiodilatin Atrial Natriuretic Factor” OR “Prepro-ANP” OR “Prepro ANP” OR “ANF Precursors” OR “Cardiodilatin Precursor” OR “Prepro-CDD-ANF” OR “Prepro CDD ANF” OR “gamma-Atrial Natriuretic Peptide” OR “gamma Atrial Natriuretic Peptide” OR “Atriopeptin Prohormone (1–126)” OR “Proatrial Natriuretic Factor” OR Pronatriodilatin OR “Atriopeptin 126” OR “Cardionatrin IV” OR “Atrial Natriuretic Factor Prohormone” OR “Atrial Natriuretic Factor (1–126)” OR “Atrial Natriuretic Peptide (1–126)” OR Atriopeptigen OR “ANF (1–126)” OR “ANP (1–126)” OR “Atrial Pronatriodilatin” OR “Pro-ANF” OR “Pro ANF” OR ProANF OR “Natriuretic Peptides” [Mesh] OR “Peptides, Natriuretic” OR “Natriuretic Peptide Hormones” OR “Peptide Hormones, Natriuretic” OR “pro-brain natriuretic peptide (1–76)” [Mesh] OR “N-terminal pro-BNP” OR “NTproBNP” OR “proBNP (1–76)” OR “proBNP(1–76)” OR “N-BNP peptide” OR “NT-BNP” OR “Amino-terminal pro-brain natriuretic peptide” OR “NT-proBNP”).