The Force Frequency Relationship in Heart Failure: an Expression of a Metabolic Problem Driving Adverse Remodelling?
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Relationship between FFR and cardiac metabolomics
研究概览
简要总结
The present investigation is a non-randomised, observational study involving an unselected but highly phenotyped cohort of patients undergoing pacemaker or defibrillator implantation from whom a small sample of fat and muscle will be taken from the operation site, and, in a subgroup, from the thigh muscle. A sample of blood wil also be taken from the vein of the heart, a peripheral vein and the artery at the wrist during the procedure at different heart rates and pacing modes, to describe how heart rate and heart contraction power relate to cardiac and peripheral metabolism.
The coded blood and tissue samples and anonymised clinical data will be stored in a Human Tissue Authority-approved freezer until analysis.
Following the procedure, during routine visits, patients' left ventricular force frequency relationship will be assessed using cardiac ultrasound and a non-invasive cardiac monitor to further phenotype the severity and progression of their heart function over 6 months. For most patients, their involvement will end at that point although they will be monitored through electronic health records on an annual basis from that point forward for up to 5 years after the end of the study (for up to ten years after that point) to gain information on the prognostic value of the metabolic and haemodynamic testing.
The present investigation will allow the investigators to advance the understanding of heart-muscle crosstalk with the goal of developing targeted interventions that could open new treatment avenues.
详细描述
RESEARCH QUESTION Hypothesis: The abnormal cardiac force-frequency relationship (FFR) and peripheral autonomic activation are the result of cardiac and peripheral metabolic abnormalities.
Fundamental aims: to determine whether impaired metabolism is a mechanism underlying the failing FFR in patients with heart failure and to determine whether diabetes mellitus is a contributing factor to the development of heart failure through its adverse effect on metabolism reflected in an abnormal FFR.
Secondary aims - this project will provide answers to a series of important questions through a single protocol which are potentially of direct and longer term importance to patients:
- What metabolic pathways are abnormal in people with heart failure, diabetes mellitus and both?
- What is the relationship between skeletal muscle metabolic abnormalities and those of the myocardium?
- Can we identify using metabolomics, a substrate or compound that underlies the metabolic abnormalities?
- What is the effect of diabetes mellitus on cardiac (glucose) and peripheral metabolism at rest and with increased heart rate?
- Is cardiac metabolism abnormal at higher heart rates despite adequate perfusion?
- Is abnormal cardiac metabolism related to that of the peripheral muscles?
- Does this 'cross-talk' have a negative influence on the FFR and how does this relationship change with increased heart rate?
- Can the improved FFR with CRT be explained by improved cardiac metabolism across the entire heart rate range?
- Is peripheral autonomic activation at higher heart rates reflected in higher activation of cardiac sympathetic tone in HFrEF?
- Do the laboratory data about muscle, fat and metabolomics relate to clinical variables, response to therapy and prognosis?
- Do the haemodynamic responses to heart rate increase predict outcomes following pacemaker insertion?
STUDY DESIGN AND SETTING This will be a UK-based, unblinded, observational, mechanistic study carried out in patients receiving a pacemaker device as standard of care.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Guideline-compliant, clinical indication for pacemaker implantation
- •Age >18 years
- •Ability to provide written informed consent
- •Persons who are legally competent and mentally able to follow the instructions of the study staff
排除标准
- •Anemia Hb <8 mg/dl
- •Patients with acute infectious diseases (e.g. pneumonia)
- •Patients with heart failure due to sepsis
- •People with acute myocardial ischemia, which is manifested, for example, by angina pectoris or ECG changes under stress
- •Patients with acute liver or kidney failure
- •Pregnant and breastfeeding women
- •People who are institutionalized on official or court orders
- •People who are dependent or employed by the sponsor or investigator
- •Taking study medication (of an investigational drug) 30 days before the start of the study
- •Known contrast allergy or eGFR <20ml/min/1.73m2
- •Pregnancy not excluded by bedside pregnancy test in premenopausal women
研究组 & 干预措施
HFrEF without DM
People with heart failure due to reduced ejection fraction
HFrEF with DM
People with heart failure due to reduced ejection fraction who also have diabetes mellitus
No HF, no DM
People without heart failure who also do not have diabetes mellitus
No HF but with DM
People without heart failure but who do have diabetes mellitus
结局指标
主要结局
Relationship between FFR and cardiac metabolomics
时间窗: At baseline
Is cardiac metabolism in patients with diabetes and diabetes with heart failure as assessed by mass spectrometry-based metabolomics and lipidomics abnormal at higher heart rates and is the degree of the impairment correlated with the heart rate at which peak contractility occurs?
次要结局
未报告次要终点
研究者
Klaus K Witte, MD
Senior Lecturer in Cardiology
University of Leeds