Hypertrophic obstructive cardiomyopathy (HOCM) is a heritable heart condition that leads to the thickening of the heart muscle and causes obstruction of blood flow, impeding it's ejection from the heart (LVOT obstruction). Often individuals with HOCM suffer from chest pain and shortness of breath due to lack of oxygen supply (ischaemia) to the heart muscle in the absence of blockages in the coronary arteries.

Despite proven advances in treatment of LVOT obstruction with the novel medication Camzyos (Mavacamten), there is a limited understanding of its effect on myocardial ischaemia.

This study, called the PEACH Trial, is designed to assess whether Camzyos also improves blood supply (perfusion) to the heart muscle in patients with HOCM. A specialised imaging technique called Positron Emission Tomography/Computed Tomography (PET-CT), using Rubidium-82 will be used to evaluate blood flow to the heart muscle before and after treatment. Camzyos is part of participants' regular clinical treatment and is not being supplied, administered, or influenced by the study in any way.

Participants with HOCM who are starting treatment with Camzyos as part of their clinical care will undergo a baseline PET-CT scan (if not already done), and a second scan after 12 months. The follow-up scan is done solely for research purposes. The scans will allow researchers to evaluate whether the medication improves myocardial perfusion in addition to relieving outflow obstruction.

The study is sponsored by the University of Manchester and funded by Bristol Myers Squibb. It will involve up to 75 participants recruited at Manchester University NHS Foundation Trust. The findings could help improve understanding of how Camzyos works and support personalised treatment approaches in HOCM.

Inclusion Criteria:

1. Written informed consent.
2. Aged 18 and over.
3. Confirmed diagnosis of Hypertrophic Obstructive Cardiomyopathy (HOCM) based on diagnostic criteria, such as unexplained left ventricular hypertrophy with a maximal wall thickness ≥15 mm in the absence of uncontrolled hypertension, valvular heart disease, or HCM phenocopies such as amyloidosis and storage disorders, and presence of either a resting or provoked peak left ventricular outflow tract (LVOT) gradient ≥30 mmHg.
4. Symptoms suggestive of myocardial ischaemia (chest pain, shortness of breath on exertion) with a clinical indication for Rb-PET.
5. Eligible for Mavacamten treatment according to standard clinical guidelines. [see: https://www.nice.org.uk/guidance/ta913/chapter/1-Recommendations\]. Mavacamten is part of participants' regular clinical treatment and is not being supplied, administered, or influenced by the study in any way.
6. PET-CT performed for clinical reasons at any time in the preceding 18 months if reported as abnormal.

Exclusion Criteria:

1. Patients with obstructive coronary artery disease (epicardial coronary stenosis >50%, assessed by either invasive coronary angiography or computed tomography angiography (CTCA). Patients will undergo the initial PET study as part of their routine clinical care. If evidence of ischaemia is identified, the standard next step would involve either CT coronary angiography or, in some cases, invasive angiography to guide further clinical management. If the angiography reveals a clear lesion responsible for the ischaemia identified on PET, the patient will not be eligible for inclusion in the study and will not be approached. Conversely, if the angiography does not identify a definitive cause for the ischaemia, it will be presumed to be of microvascular origin. In such cases, the patient becomes eligible for the study and will be approached to discuss participation and provide consent at this stage. It is important to emphasize that any angiographic procedure occurs prior to consent and as part of routine clinical care. No angiographic investigations are planned or conducted as part of the study protocol. Data from the clinical angiogram will not be included in the study, except to note a 'positive angiogram' as a reason for patient exclusion.

2. Contraindications to Mavacamten, including left ventricular ejection fraction (LVEF) less than 55%, hypersensitivity or allergic reaction to the drug.

3. Contraindication to Rubidium PET-CT, including:

   • Pregnancy or breastfeeding.
   • Severe claustrophobia.
   • Morbid obesity when the patient dimensions are beyond the scanning chamber capacity.

4. Any medical condition, which in the opinion of the Investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.

Data access is limited to the research team as per ethical and institutional approvals.