Periprocedural myocardial infarction: thresholds of (in)significance

This editorial refers to ‘Periprocedural myocardial infarction after percutaneous coronary intervention and long-term mortality: a meta-analysis’, by L. Paolucci et al., https://doi.org/10.1093/eurheartj/ehae266. Not all myocardial infarctions are created equal. The overwhelming majority of the data support the concept that spontaneous myocardial infarctions carry more prognostic weight than periprocedural myocardial infarctions.1,2 Beyond this, periprocedural myocardial infarction is controversial, at least in part due to a persisting lack of consensus on how it should be defined and applied. Open questions exist on whether definitions should be the same for patients undergoing percutaneous coronary intervention (PCI) as those undergoing coronary artery bypass grafting (CABG); which cardiac biomarker should be utilized; what thresholds of biomarker elevation should be required to diagnose a periprocedural myocardial infarction; and whether other ancillary criteria (such as ECG changes, myocardial imaging, or coronary angiography) should also be required in addition to biomarker elevations. For a definition of periprocedural myocardial infarction to have clinical utility, it must be associated with prognosis (principally mortality); otherwise, there is little purpose beyond inflating event rates to increase statistical power in clinical trials. In this issue of the European Heart Journal, Paolucci and colleagues make another contribution to the literature on periprocedural myocardial infarction.3 The authors integrate data from 19 studies with 109 568 patients. The three most commonly used definitions of periprocedural myocardial infarction were studied: the Fourth Universal Definition of Myocardial Infarction (UDMI),4 the Academic Research Consortium (ARC) 2 definition,5 and the Society of Cardiac Angiography and Interventions (SCAI) definition.6 Further categorization was based on whether biomarker elevation only was required, or whether additional data were required from ECG, angiography, or myocardial imaging. Multivariate regression analyses were performed to describe the association between each definition and all-cause mortality; cardiovascular mortality was a secondary endpoint. The authors found that using the UDMI definition led to the highest incidence of periprocedural myocardial infarction, followed by the ARC-2 definition, followed by the SCAI definition. All definitions were associated with an increased risk of all-cause death, but this association was weakest for the UDMI definition [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.32–1.97], followed by the ARC-2 definition (HR 2.07, 95% CI 1.40–3.08), and strongest for the SCAI definition (HR 3.24, 95% CI 2.36–4.44). A similar pattern was seen with cardiac death, with a weaker association with the UDMI definition (HR 1.85) and a stronger association with the SCAI definition (HR 6.14). The use of ancillary criteria (ECG changes, myocardial imaging, or coronary angiography) improved the prognostic power of the UDMI definition but not that of the SCAI definition. The study elegantly demonstrates two overarching principles when considering periprocedural myocardial infarctions: first, that each marker’s prognostic relevance is inherently dependent on the thresholds utilized in their definitions; and, second, that there is necessarily an inverse relationship between the sensitivity of a particular definition and its prognostic importance (Graphical Abstract). Highly sensitive metrics, such as the UDMI definition, will lead to an increasing incidence of periprocedural myocardial infarction with a weaker prognostic association with mortality. Conversely, periprocedural myocardial infarction occurs least often with the SCAI definition but this had the strongest association with mortality, a finding that corroborates prior evidence.7,8 Another important finding from this study is that ancillary criteria only improved the prognostic power of the UDMI definition and not of the SCAI definition. Phrased alternatively, ancillary criteria matter less if there is a large infarction by biomarker criteria. Again, this is consistent with prior work and has important implications.7,9 Coronary angiography is more commonly performed after PCI than after CABG, and therefore definitions that rely on angiographic changes may differentially increase periprocedural infarction rates solely as a function of the index revascularization modality. Furthermore, a definition that relies purely on biomarker elevations and does not incorporate imaging or other ancillary criteria would simplify clinical trial design and data collection, and potentially reduce attendant costs. There are inherent limitations associated with the use of study-level data from non-randomized studies, with the primary weakness being the pooling of data from heterogenous patient populations and varied clinical settings. Notwithstanding these, this is an important study of a contentious area. We believe that the findings support the position that stringent thresholds of biomarker elevation should be utilized for periprocedural myocardial infarction after PCI, and that prognostic relevance should be emphasized above sensitivity. This concept also exists for spontaneous myocardial infarction where the data support that the degree of biomarker elevation is related to prognostic impact.10,11 To that end, we would endorse the utilization of the SCAI definition in clinical trials of PCI as one that does not require additional qualifiers and is consistent across different revascularization strategies, and we agree with previous Editorialists that spontaneous myocardial infarction should be given precedence over periprocedural myocardial infarction.12 Again, not all myocardial infarctions are created equal, and we should make efforts to ensure we are capturing prognostically relevant infarctions and reporting them with appropriate weighting and priority. All authors declare no conflict of interest for this contribution.