The Effect of Inorganic Nitrite on Cardiac Function During Exercise in Patients with Heart Failure with Preserved Ejection Fraction (HFpEF)

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Heart failure is commonly understood to be a condition in which the heart does not pump strongly enough, leading to breathlessness. But in about half of patients with heart failure the problem is not with the heart's pumping strength at all. Rather it is due to the heart's inability to relax after each pumping squeeze. This type of heart failure is called "Heart Failure with Preserved Ejection Fraction" (HFpEF).HFpEF is a serious condition. It can cause severe breathlessness and swelling of the limbs. The breathlessness caused by HFpEF can be so severe that some patients need to be admitted to hospital for treatment. Patients with HFpEF have reduced life expectancy. A lot of research has been done to try and understand what causes HFpEF. At first it was thought that patients with HFpEF had hearts that were simply too stiff. However, we now understand that this heart stiffness is related to the stiffness of the main blood vessels in the body. At present, there are no effective treatments and there is no cure for this condition.One potential treatment for HFpEF is called nitrite, a substance which is found naturally in the body. It is good at relaxing blood vessels and we suspect it could help the heart relax. Indeed, when patients with HFpEF are given a single dose of beetroot juice (which the body converts to nitrite), they can exercise more. Our research group has done a preliminary study which suggests that if we give nitrite directly to the heart, it helps the heart relax.In this research we aim to answer the following questions: Does nitrite improve how the heart and blood vessels relax during exercise in patients with HFpEF? Furthermore, does taking beetroot juice for two weeks mean that patients with HFpEF can exercise more?We propose to carry out two studies to help us answer our research questions.In the first study, we will give 35 patients with HFpEF beetroot juice shots to drink twice a day for two weeks. Before and after the treatment period, the patients will complete an exercise test, while taking ultrasound measurements of the heart pumping function and of the main blood vessel in the neck. Patients will undergo two courses of beetroot juice treatment. In one of the two-week periods they will take normal beetroot juice ('active'). In the other they will take a specially produced version of beetroot juice which doesn't get converted to nitrite in the body (the 'placebo'). Neither the research team or the patients will know which type of beetroot juice they are taking at any given time. This study will help us answer the question of whether two week's treatment with beetroot juice allows patients with HFpEF to exercise more. By comparing the ultrasound measurements at rest and on exercise, we will be able to assess how beetroot juice affects the ability of the heart and blood vessels to relax.Sometimes patients with HFpEF need to undergo investigations to check the heart arteries and to measure the pressures inside the heart. In this second study, we would enrol 22 such patients to take part in a study where we would give either nitrite or salt water directly to the heart while the patient exercises (either on special bicycle pedals or by lifting a weight with their arm). We will place a specially-designed wire into the heart to measure changes in pressure and blood volume within the heart. We suspect that nitrite will help reduce the abnormal increases in the heart's pressure seen when patients with HFpEF exercise. This study will help us find out if this is true.We consider this research to be important because it will help us confirm a new way to help the heart relax in patients with HFpEF. Indeed, if beetroot juice were shown to be effective, this would represent an easy, cheap, and drug-free way to treat patients with HFpEF.