Determining patient-individualised placebo-controlled angina thresholds for invasive haemodynamic assessment

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-- Background --Angina is a symptom of chest pain that is thought to be caused by a reduction in blood flow, and therefore oxygen, to the heart. Angina is typically worse during exercise and is relieved with rest. The most common cause of angina is narrowing in the arteries supplying the heart. Currently, we measure the severity of a narrowing within an artery by assessing the pressure drop across the narrowing, as this tells us if the narrowing is causing a reduction in blood flow. Current guidelines recommend that if there is a pressure drop of more than 20% across a narrowing, it is called significant, and treatment with a metal stent in a procedure called percutaneous coronary intervention (PCI) is warranted. The metal stent keeps the artery open, thereby allowing blood flow to normalise and offering symptom relief.What remains unclear however, is why the current guidelines use this specific cut-off of a 20% pressure drop for symptom relief as the relationship between a pressure drop and symptoms has never been tested in a clinical study. It also remains to be determined whether one cut-off for the whole population is appropriate or rather a patient-individualised approach should be used. If this relationship between the pressure drop and symptoms is not as well-defined, then it is likely that many patients with significant angina who do not meet this strict 20% pressure drop threshold are being refused PCI that would dramatically relieve their symptoms. Equally, we may be offering PCI to lots of patients who meet this 20% threshold but have minimal symptoms and do not need the procedure. -- Objectives --1. To find the true pressure drop that causes angina for every patient.2. To determine how this pressure drop varies between patients.3. To determine how this pressure drop varies between exercise and rest for the same patient. -- Methods --We will enrol 58 patients who have symptoms of angina and are eligible for PCI, demonstrate anatomical evidence of significant narrowing in one of their arteries and have evidence of blood flow abnormalities. Symptom burden will be assessed during the pre-assessment visit using questionnaires and a symptom-based smartphone application. During the procedure, all patients will first have their narrowing treated with PCI using a metal stent to restore normal flow. The angina thresholds will then be established by progressively narrowing the coronary artery lumen with a balloon directly inside the stent, until angina just develops. This will be performed separately while the patient is exercising and resting, and the degree of narrowing that causes angina will be recorded for both. Following recovery, the identical degree of narrowing that caused angina will be re-introduced (without the patient exercising) and the exact pressure drop causing exercise angina and rest angina will be obtained separately. To eliminate reporting bias from patients and observing staff, false balloon inflations in between real inflations will be applied without their knowledge (placebo-control). -- Potential Benefits --My fellowship will be the first study to identify the haemodynamic threshold for angina under double-blinded placebo-controlled experimental conditions. If successful, this project will:1. Provide a more accurate representation of the relationship between the pressure drop across a narrowing and symptoms of angina. 2. Determine whether there is variability between patients. If considerable variability is observed, it is likely we will need to change our current clinical practice that uses a single predefined clinical threshold of 20% for the whole population to a more personalised and patient-tailored approach. 3. Determine if the thresholds during exercise (when the patient typically gets angina) is different from rest (what we measure in the cath lab).