TY - JOUR
T1 - Pathophysiology of exercise intolerance in chronic diseases
T2 - the role of diminished cardiac performance in mitochondrial and heart failure patients
AU - McCoy, Jodi
AU - Bates, Matthew
AU - Eggett, Christopher
AU - Siervo, Mario
AU - Cassidy, Sophie
AU - Newman, Jane
AU - Moore, Sarah A.
AU - Gorman, Grainne
AU - Trenell, Michael I.
AU - Velicki, Lazar
AU - Seferovic, Petar M.
AU - Cleland, John G.F.
AU - MacGowan, Guy A.
AU - Turnbull, Doug M.
AU - Jakovljevic, Djordje G.
N1 - Funding information: This study was funded by the Newcastle National Institute for Health Research (NIHR) Biomedical Research Centre in Ageing and Age Related Diseases. Dr Siervo is supported by the UK Medical Research Council investigator award, Gorman and Newman by the Welcome Trust Centre for Mitochondrial Diseases, Moore by the NIHR Clinical Academic Lectureship, Trenell by NIHR Senior Research Fellowship, and Jakovljevic by Research Councils UK Centre for Ageing and Vitality.
PY - 2017/7
Y1 - 2017/7
N2 - Objective Exercise intolerance is a clinical hallmark of chronic conditions. The present study determined pathophysiological mechanisms of exercise intolerance in cardiovascular, neuromuscular, and metabolic disorders.Methods In a prospective cross-sectional observational study 152 patients (heart failure reduced ejection fraction, n=32; stroke, n=34; mitochondrial disease, n=28; type two diabetes, n=28; and healthy controls, n=30) performed cardiopulmonary exercise testing with metabolic and haemodynamic measurements. Peak exercise O2 consumption and cardiac power output were measures of exercise tolerance and cardiac performance.Results Exercise tolerance was significantly diminished in patients compared with controls (ie, by 45% stroke, 39% mitochondria disease, and 33% diabetes and heart failure, p<0.05). Cardiac performance was only significantly reduced in heart failure (due to reduced heart rate, stroke volume, and blood pressure) and mitochondrial patients (due reduced stroke volume) compared with controls (ie, by 53% and 26%, p<0.05). Ability of skeletal muscles to extract oxygen (ie, arterial-venous O2 difference) was diminished in mitochondrial, stroke, and diabetes patients (by 24%, 22%, and 18%, p<0.05), but increased by 21% in heart failure (p<0.05) compared with controls. Cardiac output explained 65% and 51% of the variance in peak O2 consumption (p<0.01) in heart failure and mitochondrial patients, whereas arterial-venous O2 difference explained 69% (p<0.01) of variance in peak O2 consumption in diabetes, and 65% and 48% in stroke and mitochondrial patients (p<0.01).Conclusions Different mechanisms explain exercise intolerance in patients with heart failure, mitochondrial dysfunction, stroke and diabetes. Their better understanding may improve management of patients, their stress tolerance and quality of life.
AB - Objective Exercise intolerance is a clinical hallmark of chronic conditions. The present study determined pathophysiological mechanisms of exercise intolerance in cardiovascular, neuromuscular, and metabolic disorders.Methods In a prospective cross-sectional observational study 152 patients (heart failure reduced ejection fraction, n=32; stroke, n=34; mitochondrial disease, n=28; type two diabetes, n=28; and healthy controls, n=30) performed cardiopulmonary exercise testing with metabolic and haemodynamic measurements. Peak exercise O2 consumption and cardiac power output were measures of exercise tolerance and cardiac performance.Results Exercise tolerance was significantly diminished in patients compared with controls (ie, by 45% stroke, 39% mitochondria disease, and 33% diabetes and heart failure, p<0.05). Cardiac performance was only significantly reduced in heart failure (due to reduced heart rate, stroke volume, and blood pressure) and mitochondrial patients (due reduced stroke volume) compared with controls (ie, by 53% and 26%, p<0.05). Ability of skeletal muscles to extract oxygen (ie, arterial-venous O2 difference) was diminished in mitochondrial, stroke, and diabetes patients (by 24%, 22%, and 18%, p<0.05), but increased by 21% in heart failure (p<0.05) compared with controls. Cardiac output explained 65% and 51% of the variance in peak O2 consumption (p<0.01) in heart failure and mitochondrial patients, whereas arterial-venous O2 difference explained 69% (p<0.01) of variance in peak O2 consumption in diabetes, and 65% and 48% in stroke and mitochondrial patients (p<0.01).Conclusions Different mechanisms explain exercise intolerance in patients with heart failure, mitochondrial dysfunction, stroke and diabetes. Their better understanding may improve management of patients, their stress tolerance and quality of life.
KW - cardiac function
KW - exercise limitations
KW - heart failure
KW - oxygen consumption
UR - http://www.scopus.com/inward/record.url?scp=85026434605&partnerID=8YFLogxK
U2 - 10.1136/openhrt-2017-000632
DO - 10.1136/openhrt-2017-000632
M3 - Article
AN - SCOPUS:85026434605
SN - 2053-3624
VL - 4
SP - 1
EP - 8
JO - Open Heart
JF - Open Heart
IS - 2
M1 - e000632
ER -