Angina After PCI: a Systems Medicine Study

Residual angina post-PCI, defined as adjudicated, angina (Seattle Angina Questionnaire Angina Frequency (SAQ-7-AF) score <90) occurring within one year of percutaneous coronary intervention.

Angina severity will be assessed using the Seattle Angina Questionnaire Summary Score.

Myocardial perfusion reserve (MPR) within the distribution of the target coronary artery/ies revealed by cardiovascular magnetic resonance (CMR) imaging.

Fractional flow reserve after percutaneous coronary intervention, reflecting the success of the procedure.

Coronary flow reserve (CFR) post-PCI. Coronary flow reserve takes account of adenosine-mediated vasodilatation of the coronary artery and microcirculation. A CFR <2.0 is abnormal, a CFR 2.0-<2.5 is impaired and a CFR>2.5 is normal.

Index of microvascular resistance (IMR) post-PCI. IMR reflects adenosine-mediated minimal microvascular resistance. An IMR >=25 is abnormal.

Microvascular dysfunction is defined as a CFR<2.5 and/or an IMR>=25 post-PCI.

Health-related quality of life will be assessed using the EuroQol-5D 5 Level (5L) questionnaire. EQ-5D-5L is a health status questionnaire that measures five dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression

The Duke Activity Status Index (DASI) is a self-administered questionnaire with a 12-item scale that estimates physical functional capacity, cardiorespiratory function and metabolic equivalents (METs).

Brief Illness Perception Questionnaire (BIPQ) is a nine-item scale that measures the cognitive and emotional representations of illness.

Patient Health Questionnaire-4 (PHQ-4) is a self-reported questionnaire to assess for anxiety and depression over the last 2 weeks. Scores are rated as normal (0-2), mild (3-5), moderate (6-8), and severe (9-12). Total score ≥3 for first 2 questions suggests anxiety.

The Institute for Medical Technology Assessment (iMTA) Productivity Cost Questionnaire (iPCQ) is a generic tool to measure productivity losses.

The Rockwood Clinical Frailty Scale (CFS) is a tool to summarize the overall level of fitness or frailty of an older individual.

Serious adverse events (SAE) post-enrolment will be assessed using electronic health records without the need for participant contact. The SAE of interest are pre-specified in the protocol. Where e-health records are not an option, then an annual contact with the participant should be undertaken to assess for SAE. The final visit is defined as when the last participant has completed 12 months follow-up. The minimum duration of follow-up will be 12 months and the maximum duration of follow-up is anticipated to be up to 48 months. Longer term follow-up to 20 years will be undertaken using electronic health record linkage.

Abnormal lipid metabolism, and hyperlipidemia, mediate atherogenesis. The circulating concentrations of low density lipoprotein, a proatherogenic lipid, will be assessed.

Systemic inflammation may underlie the pathogenesis of resistant angina. Systemic inflammation will be assessed by measurement of the circulating concentration of C-reactive protein.

Glycemic status may underlie the pathogenesis of resistant angina. Cardiometabolic status will be assessed by measurement of the circulating concentration of glycated hemoglobin (HbA1c), a metabolic biomarker.

The circulating concentration of troponin, measured using a high sensitivity assay, reflects ischemic myocardial injury or infarction.

Abnormal lipid metabolism, and hyperlipidemia, mediate atherogenesis. The circulating concentrations of lipoprotein(a), a proatherogenic lipid, will be assessed.

Microvascular dysfunction is defined as a composite outcome including the occurence of CFR<2.5 and/or an IMR>=25 and/or microvascular spasm (acetylcholine).

Since acetylcholine-mediated microvascular spasm may reflect microvascular dysfunction, in the subpopulation also undergoing acetylcholine coronary reactivity testing, the microvascular dysfunction outcome measure will include the response to acetylcholine (yes/no), and CFR<2.5 and/or IMR>=25.

The ratio of stress subendocardial myocardial blood flow / stress subepicardial myocardial blood flow.

Myocardial blood flow is estimated as ml/min/g myocardial tissue on the American Heart Association model of myocardial segments.

Extent of impaired hyperemic myocardial blood flow (MBF, ml/min/g), defined as the ordinal number of segments with impaired peak hyperemic myocardial blood flow according to consensus-based, reference thresholds (PMID: 30772231). A regional perfusion defect is defined as myocardial blood flow <2.0 ml/min/g in one or more segments. If the perfusion defect is global (rather than regional) and suspected as being due to microvascular disease, then the MBF threshold is <2.25 ml/min/g.

Coronary vasomotor dysfunction in response to intracoronary infusion of acetylcholine. Vasomotor dysfunction is defined as coronary artery spasm and/or microvascular spasm according to contemporary diagnostic criteria (PMID: 39210710).

Hyperemic myocardial blood flow (MBF, ml/min/g) in all segments.