upregulating the nitric oxide pathway to restore autonomic phenotype (untrap).

Conditions: Heart Failure; Arrhythmia

Summary: autonomic nervous system dysfunction is known to be associated with an increased risk of heart rhythm abnormalities and sudden cardiac death (scd) in patients with chronic heart failure - a condition affecting millions of people worldwide. the nitric oxide pathway has been identified as being involved in mediating the effects of the autonomic nervous system on the heart. recent studies have shown that dietary nitrates can increase the availability of nitric oxide in the body. this study hopes to find out if dietary nitrate supplementation can help to improve cardiac and autonomic function in patients with heart failure and autonomic dysfunction and reduce the risk of arrhythmias.

20 participants enrolled at the university hospitals of leicester nhs trust will be invited to take a beetroot juice supplement, which naturally contains a high concentration of nitrates, and a nitrate-free (placebo) beetroot supplement. in a double blind way, participants will be randomised to the order in which they receive the 2 treatments with crossover of the treatments. there will be a washout period between the two treatments. in order to assess cardiac and autonomic function, and risk of heart rhythm abnormalities, tests will be carried out before and after each treatment period hypotheses: * nitrate supplementation reverses the autonomic dysfunction seen in chronic heart failure (chf) * markers of prognostic significance for predicting scd, including qt variability index and cardiac restitution properties (r2i2, pers), are normalised by nitrate supplementation in patients with chf. * nitrate supplementation results in functional improvement in chf patients.

Eligibility criteria:
inclusion criteria: * participant is willing and able to give informed consent for participation in the study. * male or female. * diagnosed with chronic heart failure - nyha ii-iii * reduced heart rate variability * left ventricle ejection fraction (lvef) of ≤40% * sinus rhythm on 12 lead ecg * must have an adequate understanding of written and spoken english * female participants of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter * able (in the investigators opinion) and willing to comply with all study requirements non-invasive programmed stimulation (nips) sub-study inclusion criteria: * participant is willing and able to give informed consent for participation in the study * patients has a pre-existing icd device with right ventricular apical lead exclusion criteria: * myocardial infarction or coronary revascularization within the last 6 months before study enrolment * nyha class iv heart failure symptoms * persistent atrial fibrillation (af)/atrial flutter, or paroxysmal af with frequent recent episodes of prolonged af * patients taking any other nitrate containing medication or supplement (e.g. isosorbide mononitrate, gtn) * patients taking proton pump inhibitors * severe pulmonary disease * significant renal impairment (egfr\<15) * active cancer with life expectancy \< 1year * patients with significant diabetic or other autonomic neuropathy * current or recent (within the last year) cigarette smokers * female participants who are pregnant, lactating or planning pregnancy during the course of the study. * due to undergo any scheduled elective surgery or other procedures requiring general anaesthesia during the study. * participant who is inappropriate for placebo therapy * subjects who do not have an adequate understanding of written and spoken english * any other significant disease or disorder, which in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study. * participants who have participated in another research study involving an investigational product in the past 12 weeks

Keywords: nitrate