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

无机亚硝酸盐对射血分数保留的心力衰竭（HFpEF）患者运动时心功能的影响

• 批准号: MR/R017751/1
• 负责人: Kevin O'Gallagher
• 金额: $ 31.11万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR017751%2F1
• 关键词: Effect; Inorganic; Nitrite; Cardiac; Function

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.

心力衰竭通常被理解为心脏泵血不够有力，导致呼吸困难的一种情况。但在大约一半的心力衰竭患者中，问题根本不在于心脏的泵送强度。相反，这是由于心脏在每次挤压后无法放松。这种类型的心力衰竭被称为“保留射血分数的心力衰竭”（HFpEF）。HFpEF是一种严重的疾病。它会导致严重的呼吸困难和四肢肿胀。HFpEF引起的呼吸困难可能非常严重，一些患者需要住院治疗。HFpEF患者的预期寿命缩短。人们做了很多研究，试图了解导致高强度脉冲脉冲的原因。起初，人们认为HFpEF患者的心脏太僵硬了。然而，我们现在了解到，这种心脏僵硬与体内主要血管的僵硬有关。目前，没有有效的治疗方法，也没有治愈这种疾病的方法。治疗HFpEF的一种潜在方法是亚硝酸盐，这是一种在人体内自然存在的物质。它能很好地放松血管，我们怀疑它能帮助心脏放松。事实上，当患有HFpEF的患者被给予单剂量的甜菜根汁（身体将其转化为亚硝酸盐）时，他们可以进行更多的运动。我们的研究小组做了一项初步研究，表明如果我们直接给心脏注入亚硝酸盐，它会帮助心脏放松。在这项研究中，我们旨在回答以下问题：亚硝酸盐是否能改善HFpEF患者运动时心脏和血管的放松？此外，服用甜菜根汁两周是否意味着HFpEF患者可以进行更多的运动？我们建议进行两项研究来帮助我们回答我们的研究问题。在第一项研究中，我们将给35名患者注射HFpEF甜菜根汁，每天喝两次，持续两周。在治疗前后，患者将完成一项运动测试，同时对心脏泵血功能和颈部主要血管进行超声测量。患者将接受两个疗程的甜菜根汁治疗。在为期两周的时间里，他们将服用普通的甜菜根汁（“活性”）。在另一组中，他们将服用一种特制的甜菜根汁，这种甜菜根汁不会在体内转化为亚硝酸盐（“安慰剂”）。研究小组和患者都不知道他们在任何时候喝的是哪种类型的甜菜根汁。这项研究将帮助我们回答这样一个问题：两周的甜菜根汁治疗是否能让HFpEF患者进行更多的运动。通过比较休息和运动时的超声波测量结果，我们将能够评估甜菜根汁是如何影响心脏和血管放松的能力的。有时HFpEF患者需要接受检查，以检查心脏动脉并测量心脏内部的压力。在第二项研究中，我们将招募22名这样的患者参加一项研究，我们将在患者锻炼时（在特殊的自行车踏板上或用手臂举重）直接向心脏注入亚硝酸盐或盐水。我们将把一根特别设计的导线放入心脏，测量心脏内压力和血容量的变化。我们怀疑，亚硝酸盐将有助于减少在HFpEF患者运动时出现的心脏压力异常升高。这项研究将帮助我们找出这是否属实。我们认为这项研究很重要，因为它将帮助我们确定一种帮助HFpEF患者心脏放松的新方法。事实上，如果甜菜根汁被证明是有效的，这将是一种简单、廉价、无药的治疗HFpEF患者的方法。

项目成果

Effect of Percutaneous Left Ventricular Unloading on Coronary Flow and Cardiac Coronary Coupling in Patients Undergoing High-Risk Percutaneous Coronary Intervention.

经皮左心室减负荷对接受高风险经皮冠状动脉介入治疗的患者冠状动脉血流和心脏冠状动脉耦合的影响。

• DOI: 10.1161/circinterventions.120.010454
• 发表时间: 2021
• 期刊: Circulation. Cardiovascular interventions
• 作者: Briceno N

Diagnostic signature for heart failure with preserved ejection fraction (HFpEF): a machine learning approach using multi-modality electronic health record data.

具有保留的射血分数（HFPEF）的心力衰竭的诊断签名：使用多模式电子健康记录数据的机器学习方法。

• DOI: 10.1186/s12872-022-03005-w
• 发表时间: 2022-12-26
• 期刊: BMC cardiovascular disorders
• 影响因子: 2.1

SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care.

• DOI: 10.1038/s41467-021-23494-1
• 发表时间: 2021-06-07
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Gutmann C;Takov K;Burnap SA;Singh B;Ali H;Theofilatos K;Reed E;Hasman M;Nabeebaccus A;Fish M;McPhail MJ;O'Gallagher K;Schmidt LE;Cassel C;Rienks M;Yin X;Auzinger G;Napoli S;Mujib SF;Trovato F;Sanderson B;Merrick B;Niazi U;Saqi M;Dimitrakopoulou K;Fernández-Leiro R;Braun S;Kronstein-Wiedemann R;Doores KJ;Edgeworth JD;Shah AM;Bornstein SR;Tonn T;Hayday AC;Giacca M;Shankar-Hari M;Mayr M
• 通讯作者: Mayr M

Interaction Between Race, Ethnicity, Severe Mental Illness, and Cardiovascular Disease.

• DOI: 10.1161/jaha.121.025621
• 发表时间: 2022-06-21
• 期刊: JOURNAL OF THE AMERICAN HEART ASSOCIATION
• 影响因子: 5.4
• 作者: O'Gallagher, Kevin;Teo, James Th;Shah, Ajay M.;Gaughran, Fiona
• 通讯作者: Gaughran, Fiona

Association of cardiometabolic microRNAs with COVID-19 severity and mortality.

• DOI: 10.1093/cvr/cvab338
• 发表时间: 2022-01-29
• 期刊: Cardiovascular research
• 影响因子: 10.8
• 作者: Gutmann C;Khamina K;Theofilatos K;Diendorfer AB;Burnap SA;Nabeebaccus A;Fish M;McPhail MJW;O'Gallagher K;Schmidt LE;Cassel C;Auzinger G;Napoli S;Mujib SF;Trovato F;Sanderson B;Merrick B;Roy R;Edgeworth JD;Shah AM;Hayday AC;Traby L;Hackl M;Eichinger S;Shankar-Hari M;Mayr M
• 通讯作者: Mayr M