Angina (Stable), Ischemic Heart Disease (IHD)
Conditions
Keywords
Angina, Microvascular angina, Percutaneous coronary intervention, Systems medicine, Health economics, cohort study, coronary artery disease, Cardiovascular magnetic resonance imaging, Coronary physiology, Health-related quality of life, Clinical outcomes
Brief summary
Angina may persist or recur in patients treated by coronary angioplasty. The angioplasty involves a balloon treatment to open a blocked heart blood vessel and usually a stent (thin metal tube) is placed. Stents do not always improve symptoms and may make symptoms worse. Sometimes a drug-eluting-balloon is used instead of a stent. This balloon coats the inside of the blood vessel to prevent re-narrowing. Research is needed to clarify the causes of ongoing angina and its impact on patients and the NHS, and to identify which patients will or will not benefit from a stent (hence avoiding over-treatment in the future). We plan a 5-year UK-wide multicenter study involving up to 600 patients with angina undergoing coronary angioplasty (with or without a stent). They will initially have a heart MRI scan. We will assess what might influence the recurrence of angina in the year after the angioplasty procedure. We will measure small blood vessel function in the heart and the amount of plaque persisting after PCI. Patients who report angina after coronary angioplasty usually have a second invasive angiogram. Instead, we will invite patients to have a heart MRI scan allowing us to also assess whether this scan might be more useful than a repeat angiogram in guiding clinical care. We will collaborate with life scientists, mathematicians, statisticians, and health economists to better understand causes and health economic implications of angina arising after coronary angioplasty procedures.
Detailed description
Background: Prior studies indicate that potentially one in three patients may experience angina within 12 months of undergoing percutaneous coronary intervention (PCI). Hypothesis: 1) Diffuse coronary atherosclerosis and/or microvascular dysfunction impair myocardial blood flow (MBF) leading to angina post-PCI. Design: A 5-year interdisciplinary program with 3 scientific work-packages (WPs): 1) Clinical, 2) Systems medicine, and 3) Health Economics. WP1) Cohort study In 4 or more centers in the United Kingdom, 600 patients with angina will undergo stress/rest perfusion cardiovascular magnetic resonance (CMR) imaging with inline pixel-mapping of MBF (ml/min/g) and then coronary physiology measured during PCI. Patient reported outcome measures will be collected routinely during follow-up to 12 months. Primary outcome: Adjudicated, residual angina (Seattle Angina Questionnaire Angina Frequency (SAQ-7-AF) score \<90). Nested case-control study: stress perfusion CMR (MBF culprit artery territory, primary outcome) in approximately 200 patients reporting residual angina and 50 consecutive asymptomatic controls (all post-PCI). Clinically indicated coronary angiography including physiology tests (change from baseline measurement) and acetylcholine testing will be undertaken in approximately 120 patients. WP2) Systems medicine (n=600) using biostatistics to identify multivariable baseline associates (clinical, coronary physiology, haemodynamics, circulating biomarkers (DNA, RNA, protein) of the SAQ-7-AF score (range 0 (Severe) - 100 (no angina)) post-PCI. WP3) Health economics of NHS resource utilization and value of information (VoI) modelling to design stratified medicine trials. Value: Identification of mechanisms to inform downstream diagnostic and therapeutic strategies for angina post-PCI.
Interventions
DIAGNOSTIC_TESTCardiovascular magnetic resonance imaging
Observational diagnostic tests will include adenosine-stress perfusion cardiovascular magnetic resonance imaging before undergoing percutaneous coronary intervention.
DIAGNOSTIC_TESTCoronary physiology
Invasive coronary function tests using a diagnostic guidewire (PressureWire-X, Abbott), thermodilution, intravenous or intracoronary infusion of adenosine and intracoronary infusions of acetylcholine.
Sponsors
Robertson Centre for Biostatistics - University of Glasgow
British Heart Foundation
Abbott Medical Devices
CoreAalst BV
National Heart, Lung, and Blood Institute (NHLBI)
NHS National Waiting Times Centre Board
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
BEFORE INVASIVE MANGEMENT 1. Angina by SAQ-7 Angina Frequency Score \<90\* 2. Stress CMR imaging\* DURING INVASIVE MANAGEMENT 3. PCI (successful) 4. Coronary physiology assessment post-PCI.
Exclusion criteria
1. Age \<=18 years 2. Acute MI within 30 days 3. Invasive management \>90 days after stress CMR 4. Inability to comply with the protocol 5. Lack of written informed consent. 6. Pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Residual angina after percutaneous coronary intervention. | From enrolment to 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Coronary flow reserve after percutaneous coronary intervention | 24 hours | 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. |
| Microvascular dysfunction after percutaneous coronary intervention | 24 hours | Microvascular dysfunction is defined as a CFR\<2.5 and/or an IMR\>=25 post-PCI. |
| Health-related quality of life | From enrolment to 12 months | 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 |
| Physical function | From enrolment to 12 months | 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). |
| Illness perception | From enrolment to 12 months | Brief Illness Perception Questionnaire (BIPQ) is a nine-item scale that measures the cognitive and emotional representations of illness. |
| Anxiety and depression | From enrolment to 12 months | 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. |
| Productivity loss | From enrolment to 12 months | The Institute for Medical Technology Assessment (iMTA) Productivity Cost Questionnaire (iPCQ) is a generic tool to measure productivity losses. |
| Fraility | From enrolment to 12 months | 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 | From enrolment to 12 months | 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. |
| Low density lipoprotein | From enrolment to 12 months | Abnormal lipid metabolism, and hyperlipidemia, mediate atherogenesis. The circulating concentrations of low density lipoprotein, a proatherogenic lipid, will be assessed. |
| Angina | From enrolment to 12 months | Angina severity will be assessed using the Seattle Angina Questionnaire Summary Score. |
| Myocardial perfusion reserve | From enrolment to 12 months | Myocardial perfusion reserve (MPR) within the distribution of the target coronary artery/ies revealed by cardiovascular magnetic resonance (CMR) imaging. |
| Fractional flow reserve post-percutaneous coronary intervention | 24 hours | Fractional flow reserve after percutaneous coronary intervention, reflecting the success of the procedure. |
| Index of microvascular resistance after percutaneous coronary intervention | 24 hours | Index of microvascular resistance (IMR) post-PCI. IMR reflects adenosine-mediated minimal microvascular resistance. An IMR \>=25 is abnormal. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Myocardial injury | From enrolment to 12 months | The circulating concentration of troponin, measured using a high sensitivity assay, reflects ischemic myocardial injury or infarction. |
| Lipoprotein(a) | From enrolment to 12 months | Abnormal lipid metabolism, and hyperlipidemia, mediate atherogenesis. The circulating concentrations of lipoprotein(a), a proatherogenic lipid, will be assessed. |
| Microvascular dysfunction (acetylcholine test population) | 24 hours | 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. |
| Microvascular blood flow | From enrolment to 12 months | 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. |
| Impaired myocardial blood flow | From enrolment to 12 months | 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 | From enrolment to 12 months | 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). |
| Myocardial blood flow (hyperaemic, global) | From enrolment to 12 months | Hyperemic myocardial blood flow (MBF, ml/min/g) in all segments. |
| Glycemic status | From enrolment to 12 months | 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. |
| Inflammation | From enrolment to 12 months | Systemic inflammation may underlie the pathogenesis of resistant angina. Systemic inflammation will be assessed by measurement of the circulating concentration of C-reactive protein. |
Countries
United Kingdom
Outcome results
None listed