Background and rationale
Cardiovascular magnetic resonance (CMR) is a non-invasive imaging technique that assesses heart structure and function with high spatial and temporal resolution. The use of CMR has increased in recent years in all subgroups of acute coronary syndrome (ACS) patients, including those who activate the primary percutaneous coronary intervention (PPCI) pathway.1 It is not clear whether or not having CMR influences patient management or reduces the length of hospital stay or the risk of major adverse cardiovascular events (MACEs) in these patients. Systematic reviews from 2014 highlighted the lack of high-quality, adequately powered studies to establish the prognostic value of CMR findings in patients who activate the PPCI pathway.2,3 Similarly, few studies have assessed how CMR changes patient management, despite the fact that cardiologists believe that CMR brings about important changes in management.4
Primary percutaneous coronary intervention
Primary percutaneous coronary intervention is the primary therapeutic approach for restoring blood flow to the heart in ACS patients who have had a ST-elevation myocardial infarction (STEMI). Currently, across the UK ≈97% of patients with a STEMI who received any reperfusion treatment were treated with PPCI.5 Management of the in-hospital stay and follow-up after PPCI is determined by the final infarct size, the presence or absence of comorbidities and patient characteristics. About 10% of patients with ACS who activate the PPCI pathway (i.e. those that present with chest pain and ST-elevation or chest pain and new-onset left bundle branch block on electrocardiogram) are found to have unobstructed coronary arteries on angiography and, therefore, do not receive PPCI. There are no long-term outcome data from well-designed, multicentre trials on CMR use in different subgroups of patients who activate the PPCI pathway. There are also no studies reporting on the cost-effectiveness of CMR in these patients (or indeed patients from other clinical areas), which makes decision-making regarding the provision of CMR services within the NHS difficult.
Subgroups of patients who activate the primary percutaneous coronary intervention pathway and may benefit from cardiovascular magnetic resonance
Two subgroups of patients were identified in the protocol as having the potential to benefit from CMR: (1) patients with multivessel disease and (2) patients with unobstructed coronary arteries on angiography.
It is estimated that 40–65% of the patients presenting with a STEMI have multivessel disease (depending on the baseline characteristics, e.g. age, of the population studied).6–11 There is ongoing debate about the optimal treatment strategy for these patients. Three main treatment management strategies have been proposed/are currently used: (1) conservative, PPCI of the infarcted artery followed by medical therapy (unless ischaemia occurs), (2) staged, in which only the infarct-related artery is treated acutely and other lesions are treated at a later date and (3) aggressive, percutaneous coronary intervention (PCI) of all significant lesions at the time of PPCI.
The role of CMR in patients with multivessel disease is undefined. CMR allows the volume of ischaemic or poorly perfused myocardium to be quantified but it is not known whether or not access to CMR to plan further revascularisation influences management. Since the Primary percutaneous coronary Intervention Pathway Activation (PIPA) study was commissioned, there has also been a rapid increase in the use of fractional flow reserve (FFR) testing (a guide wire-based procedure done through a standard diagnostic catheter at the time of a coronary angiography) to assess ischaemia; this technology is available to interventional cardiologists in the catheter laboratory. CMR is comparable to FFR for detecting ischaemia; studies have shown excellent diagnostic accuracy of perfusion CMR to detect areas of ischaemia identified by FFR.12,13 However, while FFR may be appropriate in symptomatic, high-risk patients for whom the benefit of an invasive approach to ischaemia testing may outweigh the risks (i.e. the likelihood of revascularisation is high; therefore, lesions can be revascularised at the same time as the FFR), the benefit is less clear in asymptomatic multivessel disease patients. CMR may, therefore, have a role in selecting patients who will receive the greatest benefit from these invasive procedures. The non-inferiority of CMR in managing patients with multivessel disease is the subject of the magnetic resonance perfusion imaging to guide management of patients with stable coronary artery disease (MR-INFORM) trial.14
The reported variation in the incidence of normal coronary angiograms in patients activating the PPCI pathway is between 3% and 16%.15,16 It is in this group that cardiologists believe that CMR has the greatest potential to change patient management. In these patients, the lack of an accurate diagnosis may result in inappropriate treatment and/or follow-up,17,18 associated with a poorer prognosis.19 A definitive diagnosis of myocardial infarction (MI) or not is also important so that these patients can be managed and followed up appropriately. Studies have shown that CMR can facilitate differential diagnosis in the context of a normal coronary angiogram,20–22 providing a definitive diagnosis (e.g. MI, myocarditis, Takotsubo cardiomyopathy) in 65–90% of these patients.20,23,24 Although the prognostic implications of non-MI CMR abnormalities are not known, two studies showed that the pattern of CMR abnormalities in myocarditis was predictive of long-term outcome.25,26
The benefit of CMR to other subgroups of patients who activate the PPCI pathway is less clear. However, given that not all of these patients will have access to centres with dedicated CMR facilities, there is potential for health inequality across the UK, which needs to be identified. Therefore, the population of interest for this study (target population) includes all ACS patients who activate the PPCI pathway, regardless of whether or not they receive PPCI.
Rationale for the study
We wanted to set up a multicentre, prospective cohort study (registry) in ACS patients who activate the PPCI pathway by linking routinely collected data from hospital information systems (HISs) with follow-up data from Hospital Episode Statistics (HES) and the Office for National Statistics (ONS). The aims of the registry were to document CMR activity in patients who activate the PPCI pathway and to provide information on CMR use, uptake over time, patients’ characteristics associated with being referred for CMR, the impact of CMR on patient management (e.g. early discharge of a patient with a normal coronary angiogram or the placement of an additional stent for a patient with multivessel disease) and the prognostic value of CMR after PPCI.
We were uncertain whether or not it would be feasible to set up a registry in this patient population using routinely collected data. In particular, we were uncertain if we could (1) easily identify the eligible population, (2) implement a ‘light-touch’ consent system across multiple hospitals and (3) extract and link data sets from multiple HISs in different hospitals. We also wanted (4) to provide a reliable estimate of the CMR rate in patients who activate the PPCI pathway and (5) to define a ‘proxy’ primary composite outcome, acceptable to cardiologists and other stakeholders (e.g. clinical commissioners) as representing a clinically important change in management as a result of an eligible patient having undergone CMR (e.g. expected to prevent future MACEs). Item number 5 was included so that the registry would be able to assess effectiveness in the medium term. A long-term objective of the registry would be to compare the incidence of MACEs in patients who do or do not have CMR after the index event, but the low frequency of MACEs means that the study would have to accrue over 37,000 subjects to detect a clinically important reduction in the incidence of MACEs with adequate power.