Nitrite in Hypertrophic Cardiomyopathy (HCM) Study

Mechanistic Study of the Effect of Inorganic Sodium Nitrate on Cardiac and Skeletal Muscle Metabolic Efficiency in Patients With Hypertrophic Cardiomyopathy

Inorganic nitrate, which is found at high levels in green leafy vegetables, is reduced to nitrite by bacteria in the mouth, swallowed, and absorbed in the stomach into the blood. Studies have shown that increasing the blood levels of nitrite improves the way that muscles use oxygen and energy during exercise, and potentially blood flow.

Some people (~1 in 500) suffer from a type of genetic heart condition known as hypertrophic cardiomyopathy (HCM). This condition means that the muscle in the heart does not use energy well and becomes larger than average, meaning that they have to tap into the heart's 'energy reserves'. It is not known if nitrite has the same beneficial effects on heart muscle as on other muscles in the body. Our study will explore the mechanism by which nitrite may improve the function and energy status of the heart in HCM.

Inclusion Criteria:

• Male or female, aged between 18 and 80 years.
• Able to provide informed consent.
• Able to understand basic instructions in English.
• A diagnosis of hypertrophic cardiomyopathy based on conventional transthoracic echocardiogram guidelines: left ventricular wall thickness >1.5cm in the absence of sufficient alternative cause.
• Exercise limited by symptoms on exertion (NYHA Class II symptoms or greater).
• PeakVO2 <80% on baseline CPEX.
• The absence of resting LV outflow tract obstruction (peak gradient <30 mm Hg) on TTE.

Exclusion Criteria:

• Significant medical, surgical or psychiatric disease that in the opinion of the patient's attending physician would affect subject safety or influence the study outcome.
• Contraindications for undergoing MRI.
• Hypotension with a systolic blood pressure <90mmHg.
• Severe anaemia with a plasma haemoglobin level <8.0g/dL.
• Known glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD deficiency measured at screening in males of African, Asian or Mediterranean decent.
• Female subjects of childbearing potential.
• Haemodynamically significant valve disease.
• Predisposed to acute on chronic limb ischemia evident from a history of claudication or known peripheral arterial disease.