None listed
Conditions
Brief summary
Exercise intolerance is a major cause of morbidity and a predictor of mortality in patients with heart failure (HF). Although many patients with HF have a dilated left ventricle and reduced ejection fraction, approximately 50% of patients have clinical manifestations of HF with a normal sized heart and normal systolic function. As such, HF is now categorised as reduced (HFrEF) vs preserved (HFpEF) ejection fraction. An important distinction of HFpEF patients is that traditional pharmacological therapies used to treat HFrEF have not improved quality of life or survival. There is currently limited understanding of HFpEF pathophysiology, thus there is a need for investigations that will lead to novel therapeutic approaches in the treatment of this condition. It is now appreciated that leg muscles become dysfunctional in HF, and generate an abnormal neural signal (a 'metaboreflex') that disrupts cardiovascular and respiratory control, enhancing ventilation and breathlessness, causing exercise intolerance (EI). A similar metaboreflex occurs within respiratory muscles, which reduces blood flow to the active limbs in these patients, exacerbating the metaboreflex arising from the legs in a detrimental positive-feedback manner, hastening the onset of breathlessness and EI. However, no studies have directly compared this reflex physiology in HFrEF and HFpEF. This proposal aims to identify metaboreflex contribution to EI by determining if the leg and respiratory muscle metaboreflexes contribute equally to EI in both HFrEF and HFpEF, their influence on cardiac function, and if exercise training attenuates metaboreflex signalling. The outcomes of this proposal will have clinical relevance and lead to the development of novel therapeutic interventions, through a combination of exercise prescription and pharmacological targeting of the metaboreflex in the early stages of HF and may lead to an elusive therapy that will improve quality of life and survival in patients with HFpEF.
Interventions
The interventions being assessed are different types of exercise training or control for eight weeks for participants with heart failure:
Arm 1: Peripheral muscle training (such as cycle ergometry for leg training)
Arm 2: Respiratory muscle training (using a threshold loading device for inspiratory muscle training, such as a POWERbreathe device)
Arm 3: Peripheral and respiratory muscle training
Arm 4: No training
Arm 5: healthy controls (no training, assessed pre and post)
Patients in the respir
The interventions being assessed are different types of exercise training or control for eight weeks for participants with heart failure: Arm 1: Peripheral muscle training (such as cycle ergometry for leg training) Arm 2: Respiratory muscle training (using a threshold loading device for inspiratory muscle training, such as a POWERbreathe device) Arm 3: Peripheral and respiratory muscle training Arm 4: No training Arm 5: healthy controls (no training, assessed pre and post) Patients in the respiratory muscle training and respiratory muscle+peripheral training groups will perform respiratory muscle training for 30 min, 5 times per week, for 8 weeks using a threshold-loading device (POWERbreathe, HaB International Ltd., Southam, UK) set at a workload equal to 60% of their maximal inspiratory pressure (MIP). Participants will breathe through the PowerBreathe device with a normal breathing frequency (not paced breathing) during these sessions. MIP will be assessed at the beginning of each training week, in order to optimise the training workload commensurate with any gains in respiratory muscle strength. Each week, 4 training sessions will be performed at home and 1 training session will be performed in the laboratory under supervision of a physiotherapist or exercise physiologist to ensure compliance with the training protocol. Participant compliance to home-based training will be monitored with home exercise diaries. The peripheral and respiratory muscle training+ peripheral muscle groups will attend the laboratory 3 times per week for the leg muscle training. At each visit, subjects will perform 30 min of constant load exercise, intermittently (5 min exercise, 1 min active recovery) on a cycle ergometer with the workload set to 65–75% of the maximal work determined via the exercise test conducted at baseline.
Sponsors
Curtin University
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
New York Heart Association (NYHA) functional class II-III outpatients will be screened to meet the following inclusion criteria: For heart failure with reduced ejection fraction (HFrEF) - i) history of ischemic or dilated cardiomyopathy, duration of HF symptoms >1 year, ii) stable symptoms > 3 months, iii) left ventricular ejection fraction less than, or equal to 35%, iv) at least one prior hospitalisation due to chronic heart failure (CHF). Patients with chronic heart failure with preserved ejection fraction (HFpEF), as defined by the Framingham criteria with ejection fraction (EF) greater than, or equal to 50% will be included if they have diastolic dysfunction determined by echocardiography (grade equal to, or greater than 1) and sinus rhythm. Healthy participants, with no prior cardiovascular disease, metabolic disease or severe condition limiting exercise capacity (such as moderate to severe respiratory conditions, neurological or musculoskeletal impairments) will be included as matched control participants (for age and sex).
Exclusion criteria
Significant valvular or pericardial disease, infiltrative or hypertrophic cardiomyopathy, cor pulmonale, significant pulmonary disease, and peripheral vascular disease.
Outcome results
None listed