Exercise Therapy to Improve Clinical Outcomes and Physiological Function in Group 2 Pulmonary Hypertension
Lead Research Organisation:
University of Leeds
Department Name: Sch of Biomedical Sciences
Abstract
Chronic heart failure (CHF) occurs when the heart muscle doesn't pump blood as well as it should. Although CHF is a heart disease, consequences of the heart problem mean that CHF actually affects the whole-body. A common and very dangerous consequence of CHF is disease of the blood vessels that supply the lungs resulting in a large increase in lung blood pressure; this is known as pulmonary hypertension. Pulmonary hypertension is actually a group of conditions. It may be caused by disease of the lung arteries themselves ("Group 1"), occur due to heart disease ("Group 2") or lung disease ("Group 3"), or as a consequence of previous blockage of the lung blood vessels ("Group 4"). However, CHF is one of the leading causes of pulmonary hypertension worldwide. For example, it is estimated that 15 million Europeans have CHF, 50-90% suffer from pulmonary hypertension.
Compared to CHF patients without pulmonary hypertension, those with pulmonary hypertension have worse symptoms, are more limited in their ability to exercise and perform routine daily tasks, have to be hospitalised more regularly, suffer greater heart damage, are more likely to need a heart transplant, and are at a much greater risk of premature death. Worryingly, drugs typically used to treat pulmonary hypertension do not typically work in CHF patients. In fact, there is currently no role for the treatment of pulmonary hypertension due to CHF using pulmonary hypertension specific medications because they are costly, do not improve symptoms, and in some cases are known to increase the risk of death in these patients. As such, there is a real and urgent medical need to identify alternative safe and effect treatments for pulmonary hypertension due to CHF.
We know that improved physical activity through exercise training benefits patients with heart disease. There is clear evidence that moderate intensity exercise (e.g., brisk walking) can improve heart, blood vessel and muscle function as well as overall health and well-being in CHF patients. Despite this, patients with any form pulmonary hypertension have traditionally be advised to avoid exercise because of concerns that may place too much stress on the heart, further worsening disease. Contrary to this historical concern, multiple studies now show that exercise training in Group 1 pulmonary hypertension is safe and improves exercise capacity and quality of life. Importantly, preliminary work from our laboratory suggests that such exercise training is also safe in CHF patients with pulmonary hypertension. However, whether exercise therapy improves short-term clinical outcomes and overall physiological function in CHF patients with pulmonary hypertension has yet to be addressed. Indeed, despite the fact that pulmonary hypertension due to heart disease is one of the most common forms of pulmonary hypertension worldwide, no research study has assessed the effect exercise therapy in Group 2 pulmonary hypertension.
The main aim of this project is to examine the safety and impact of supervised exercise training on short-term clinical outcomes (including disease severity and health-related quality-of-life), exercise capacity, heart, lung blood vessel, peripheral blood vessel (i.e. blood vessels that supply the arms and legs), and muscle function CHF patients with pulmonary hypertension. Completion of this project will provide a critical first-step towards understanding the potential clinical and therapeutic benefit of exercise training in CHF patients with pulmonary hypertension. Overall, our findings will have the potential to positively influence the therapeutic options available for the treatment of CHF patients with pulmonary hypertension, and may help drive the acceptance of exercise training delivered by local, generic heart and lung rehabilitation services as a standard of care for patients with any form of pulmonary hypertension.
Compared to CHF patients without pulmonary hypertension, those with pulmonary hypertension have worse symptoms, are more limited in their ability to exercise and perform routine daily tasks, have to be hospitalised more regularly, suffer greater heart damage, are more likely to need a heart transplant, and are at a much greater risk of premature death. Worryingly, drugs typically used to treat pulmonary hypertension do not typically work in CHF patients. In fact, there is currently no role for the treatment of pulmonary hypertension due to CHF using pulmonary hypertension specific medications because they are costly, do not improve symptoms, and in some cases are known to increase the risk of death in these patients. As such, there is a real and urgent medical need to identify alternative safe and effect treatments for pulmonary hypertension due to CHF.
We know that improved physical activity through exercise training benefits patients with heart disease. There is clear evidence that moderate intensity exercise (e.g., brisk walking) can improve heart, blood vessel and muscle function as well as overall health and well-being in CHF patients. Despite this, patients with any form pulmonary hypertension have traditionally be advised to avoid exercise because of concerns that may place too much stress on the heart, further worsening disease. Contrary to this historical concern, multiple studies now show that exercise training in Group 1 pulmonary hypertension is safe and improves exercise capacity and quality of life. Importantly, preliminary work from our laboratory suggests that such exercise training is also safe in CHF patients with pulmonary hypertension. However, whether exercise therapy improves short-term clinical outcomes and overall physiological function in CHF patients with pulmonary hypertension has yet to be addressed. Indeed, despite the fact that pulmonary hypertension due to heart disease is one of the most common forms of pulmonary hypertension worldwide, no research study has assessed the effect exercise therapy in Group 2 pulmonary hypertension.
The main aim of this project is to examine the safety and impact of supervised exercise training on short-term clinical outcomes (including disease severity and health-related quality-of-life), exercise capacity, heart, lung blood vessel, peripheral blood vessel (i.e. blood vessels that supply the arms and legs), and muscle function CHF patients with pulmonary hypertension. Completion of this project will provide a critical first-step towards understanding the potential clinical and therapeutic benefit of exercise training in CHF patients with pulmonary hypertension. Overall, our findings will have the potential to positively influence the therapeutic options available for the treatment of CHF patients with pulmonary hypertension, and may help drive the acceptance of exercise training delivered by local, generic heart and lung rehabilitation services as a standard of care for patients with any form of pulmonary hypertension.
Technical Summary
Pulmonary hypertension (PH) is a hallmark of chronic heart failure (CHF) (Group 2 PH). PH causes right-ventricular failure, further worsens exercise intolerance, and increases the risk of death 2-3-fold in CHF. However, there is currently no established pharmacological treatment for PH due to CHF, and treatment of the underlying CHF alone remains the only therapeutic option in most cases. Exercise training (ExT) portends clinically-meaningful improvements in exercise tolerance, cardiac, vascular and muscular function in CHF. Contrary to historical concerns, it is now suggested that exercise therapy is safe and efficacious in patients with pulmonary arterial hypertension (Group 1 PH). Despite this recent reclassification of international guidelines, the clinical and physiological efficacy of ExT in PH-CHF (Group 2 PH) has yet to be addressed.
The overarching aim of this project is to examine the safety and impact of supervised ExT on short-term clinical outcomes, exercise capacity, cardiac, pulmonary haemodynamic and vascular function, and skeletal muscle strength in medically stable PH-CHF patients (Group 2 PH). We hypothesise that moderate intensity ExT will be safe (i.e. will not worsen disease severity) and: 1) improve health-related quality-of-life; 2) increase exercise capacity; 3) enhance left-ventricular diastolic function and lower pulmonary vascular pressures with no deleterious changes in right-ventricular function; and 4) improve vascular endothelial function and quadriceps muscle strength. Completion of the proposed research will provide a critical first-step in understanding the potential clinical and physiological efficacy of ExT in PH-CHF. Our findings will have the potential to positively influence the therapeutic options available for the treatment of PH-CHF, and may help drive the acceptance of ExT delivered by local, generic cardiac and pulmonary rehabilitation services as a standard of care for patients with pulmonary hypertension
The overarching aim of this project is to examine the safety and impact of supervised ExT on short-term clinical outcomes, exercise capacity, cardiac, pulmonary haemodynamic and vascular function, and skeletal muscle strength in medically stable PH-CHF patients (Group 2 PH). We hypothesise that moderate intensity ExT will be safe (i.e. will not worsen disease severity) and: 1) improve health-related quality-of-life; 2) increase exercise capacity; 3) enhance left-ventricular diastolic function and lower pulmonary vascular pressures with no deleterious changes in right-ventricular function; and 4) improve vascular endothelial function and quadriceps muscle strength. Completion of the proposed research will provide a critical first-step in understanding the potential clinical and physiological efficacy of ExT in PH-CHF. Our findings will have the potential to positively influence the therapeutic options available for the treatment of PH-CHF, and may help drive the acceptance of ExT delivered by local, generic cardiac and pulmonary rehabilitation services as a standard of care for patients with pulmonary hypertension
Planned Impact
This research will for the first time determine the safety and effectiveness of exercise therapy (i.e. exercise training) for improving short-term clinical outcomes, physiological function and overall health in heart disease patients who also have pulmonary hypertension. By studying the effect of exercise therapy on the function of the heart, blood vessels and the muscles this research will increase the mechanistic understanding of how exercise training may provide therapeutic benefit in heart disease patients with pulmonary hypertension.
The primary beneficiaries of this research will be patients with heart failure who also suffer from pulmonary hypertension. Pulmonary hypertension due to heart failure is the most common form of pulmonary hypertension worldwide; despite this, there is currently no established, efficacious, and agreed upon drug treatment for this type of pulmonary hypertension. Indeed, drug-therapies that specifically target pulmonary hypertension are costly, lack effectiveness, and in many cases worsen symptoms and increase the risk of death in patients with heart failure. The development of exercise training as a viable, cheap, and effective therapeutic intervention in these patients will directly impact patient health, quality-of-life, and physiological function in the short term. Long-term, the identification and implementation of exercise training as a treatment option will help improve patient's ability to undertake routine daily activities, reduce hospitalisations, decrease disease severity, ultimately enhancing overall patient longevity and well-being, with direct socio-economic benefits. Accordingly, our research outputs will positively influence the available therapeutic options for clinicians, nurses, patients and patients' associations, healthcare providers, and regulatory agencies. Resulting impact would come from: 1) updated policy-statements and treatment guidelines for pulmonary hypertension published by Government and other specialist societies (e.g., European Society of Cardiology, European Respiratory Society); and 2) the acceptance of exercise training delivered by local, generic cardiac and pulmonary rehabilitation services as a standard of care for pulmonary hypertension patients.
This research may also benefit the general population; as many as ~35% of the healthy people aged >45 years have elevated lung blood pressure, which is an independent-predictor of premature death. Exercise based interventions that help maintain normal pulmonary vascular health or reduce elevated pulmonary vascular pressures could significantly reduce the risk of developing pulmonary related cardiovascular diseases. The development of such a low-cost strategy to 'slow-down' or 'resist-against' ageing of the lung blood vessels will have important implications for quality-of-life in older people and the burden on the UK and world economies.
The researchers on the project will benefit through developing high-level scientific skills including state-of-the-art methodologies and analytical skills, and through fostering collaborative and working links with the world-leading experts (e.g., members of the Pulmonary Hypertension Association-UK). The nature of the project will equip the researchers with an array of interdisciplinary and transferable skills (e.g., working with patient groups, presenting to audiences of different backgrounds) that will positively impact their career development in academic and/or clinical research.
Our research will benefit the wider chronic disease/health-related, vascular biology and exercise science/physiology related research fields and the general public. Communication of the outcomes of this project to a wider audience - through public symposia, schools outreach programmes and press releases - will raising awareness of the causes and consequences of heart failure and pulmonary hypertension, and potential lifestyle choices that may prevent their onset.
The primary beneficiaries of this research will be patients with heart failure who also suffer from pulmonary hypertension. Pulmonary hypertension due to heart failure is the most common form of pulmonary hypertension worldwide; despite this, there is currently no established, efficacious, and agreed upon drug treatment for this type of pulmonary hypertension. Indeed, drug-therapies that specifically target pulmonary hypertension are costly, lack effectiveness, and in many cases worsen symptoms and increase the risk of death in patients with heart failure. The development of exercise training as a viable, cheap, and effective therapeutic intervention in these patients will directly impact patient health, quality-of-life, and physiological function in the short term. Long-term, the identification and implementation of exercise training as a treatment option will help improve patient's ability to undertake routine daily activities, reduce hospitalisations, decrease disease severity, ultimately enhancing overall patient longevity and well-being, with direct socio-economic benefits. Accordingly, our research outputs will positively influence the available therapeutic options for clinicians, nurses, patients and patients' associations, healthcare providers, and regulatory agencies. Resulting impact would come from: 1) updated policy-statements and treatment guidelines for pulmonary hypertension published by Government and other specialist societies (e.g., European Society of Cardiology, European Respiratory Society); and 2) the acceptance of exercise training delivered by local, generic cardiac and pulmonary rehabilitation services as a standard of care for pulmonary hypertension patients.
This research may also benefit the general population; as many as ~35% of the healthy people aged >45 years have elevated lung blood pressure, which is an independent-predictor of premature death. Exercise based interventions that help maintain normal pulmonary vascular health or reduce elevated pulmonary vascular pressures could significantly reduce the risk of developing pulmonary related cardiovascular diseases. The development of such a low-cost strategy to 'slow-down' or 'resist-against' ageing of the lung blood vessels will have important implications for quality-of-life in older people and the burden on the UK and world economies.
The researchers on the project will benefit through developing high-level scientific skills including state-of-the-art methodologies and analytical skills, and through fostering collaborative and working links with the world-leading experts (e.g., members of the Pulmonary Hypertension Association-UK). The nature of the project will equip the researchers with an array of interdisciplinary and transferable skills (e.g., working with patient groups, presenting to audiences of different backgrounds) that will positively impact their career development in academic and/or clinical research.
Our research will benefit the wider chronic disease/health-related, vascular biology and exercise science/physiology related research fields and the general public. Communication of the outcomes of this project to a wider audience - through public symposia, schools outreach programmes and press releases - will raising awareness of the causes and consequences of heart failure and pulmonary hypertension, and potential lifestyle choices that may prevent their onset.