Mechanical reperfusion via primary percutaneous coronary intervention (PCI) in combination with optimised antithrombotic therapy and antiplatelet therapy is the current gold-standard treatment for ST-segment elevated myocardial infarction (STEMI) patients. However, preventing and treating slow/no reflow continues to be a challenge. In this commentary, Giovanni Luigi De Maria and Adrian P Banning outline the age-thrombus score-index of microcirculatory resistance (ATI) tool for assessing the risk of slow/no reflow.
In a variable proportion of patients—ranging up to 40% according to one case series—restoration of patency of the epicardial segment of the infarct related artery does not translate into optimal myocardial reperfusion. This condition—summarised as an “open artery with a closed myocardium”—is known as slow/no reflow and it has its pathophysiological background in functional impairment of the coronary microvasculature. Preventing and treating no reflow is a challenge that interventional cardiologists have undertaken in the management of STEMI patients as it is associated with worse clinical outcomes.
Many strategies have been considered, ranging from pharmacological approaches to mechanical ones. However, despite encouraging initial preliminary data from feasibility and pilot studies, neutral or disappointing results became evident when these strategies were tested in large “all-comers” randomised clinical trials.
Discussing the limitations of these trials is beyond the scope of this commentary, but identification of high-risk patients, likely to receive a suboptimal outcome from conventional treatment (primary PCI with stenting and optimised antithrombotic and antiplatelet therapy), is necessary. These high-risk patients could benefit from additional or alternative therapeutic strategies and these therapies might improve outcome.
For this reason, in Oxford (UK), we have tried to explore how we can identify patients with suboptimal response to the conventional strategy and more importantly, to see if we can identify them before treatment (eg. stenting) is delivered. We have used the assessment of the index of microcirculatory resistance (IMR) in STEMI patients after blood flow restoration in the culprit vessel, but before proceeding to stenting. This parameter can depict the status of coronary microcirculation and it has been validated against cardiac magnetic resonance and clinical outcomes. Investigators, led by Dr Fearon, have described how patients with an IMR >40 at the end of primary PCI are at high risk of poor clinical outcomes in the long term.
They applied IMR at the end of the procedure, but not before proceeding to stent. In a study published in 2015 in the European Heart Journal, we showed that IMR can be measured before stenting and more importantly that age, high index of microcirculatory resistance already before stenting (pre-stenting IMR >40) and large thrombotic burden were all predictors of post-stenting impaired coronary microvasculature, expressed by a final IMR >40. This observation was preliminary to the development of the age-thrombus score-index of microcirculatory resistance (ATI) score.
The ATI score can range from 0 to 6 and it is calculated by summing the points given to each of these three variables:
- Age: >50=1 point
- Angiographic thrombus score: <4=0 point; 4=1 point; and 5=3 points
- Pre-stenting IMR: > 40 and < 100=1 point; and >100=2 points
The ATI score was initially derived to predict a post-procedural IMR >40 in a cohort of 85 STEMI patients enrolled at the Heart Centre of the John Radcliffe Hospital. The score has then been further validated in two cohorts of patients enrolled (one retrospectively and one prospectively) at the John Radcliffe Hospital in Oxford. An external validation of the ATI score was also conducted on a cohort of STEMI patients enrolled at the Erasmus Thoraxcentre in Rotterdam (The Netherlands) and at the Azienda Ospedaliero-Universitaria S. Anna in Ferrara (Italy).
In a subsequent study, published in EuroIntervention in 2016, the ATI score showed a good accuracy in predicting a post-procedural IMR> 40, with patients with ATI score ≥4 presenting a high risk of suboptimal myocardial reperfusion post-stenting.
Our latest paper, recently published in Eurointervention, shows that the ATI score has been validated against cardiac magnetic resonance. In a newly recruited cohort of patients we have recently reported that STEMI patients with ATI score ≥4 presented larger infarct size and occurrence of microvascular obstruction and intramyocardial haemorrhage at 48 hours. Additionally patients with ATI score ≥4 present larger infarct size at six months follow up with a significant trend for occurrence of negative (adverse) left ventricular remodelling and lower infarct size shrinkage.
Although further validation is required against clinical outcome, the ATI score appears to be a promising tool in both clinical and cardiac research fields. Clinically, it could be indeed used to identify (before proceeding to stenting) those patients likely to have a suboptimal response and that might benefit from alternative or additional approaches to the standard one. Theoretically, patients with ATI score ≥ 4 could indeed been considered for “deferring-stenting strategy”, more aggressive thrombus aspiration, more potent antithrombotic or antiplatelet treatment or considered for novel therapeutic strategies like pressure-controlled coronary sinus occlusion (PICSO).
We believe that by using this strategy to identify the highest risk individuals early in their clinical treatment for STEMI, new therapies can be identified and outcomes improved.
Giovanni Luigi De Maria and Adrian P Banning are both at Heart Centre, John Radcliffe Hospital, Oxford University Hospitals, NHS Trust Foundation, Oxford, UK