Reply: Culprit coronary occlusion as a stronger short-term prognostic marker over electrocardiographic pattern in acute myocardial infarction

Abstract

Singh and Lima's commentary published in World Journal of Cardiology underscores the clinical importance of integrating angiographic occlusion status into acute myocardial infarction (AMI) risk stratification. In our response, we affirm that total culprit-artery occlusion provides independent prognostic information not captured by electrocardiographic classification alone and remains a strong independent predictor of 30-day mortality even after adjustment for peak troponin levels. We address the limitations of troponin as a surrogate for infarct size and discuss potential mechanisms—including microvascular obstruction, no-reflow, and arrhythmic risk—that may explain the persistent prognostic significance of occlusion beyond infarct size. We also contextualize the association between chronic statin therapy and lower likelihood of presenting with total occlusion. Our response reinforces the emerging OMI/NOMI paradigm as a more appropriate approach for AMI risk assessment than ST-elevation per se.

Key Words: Infarct-related artery occlusion; Electrocardiographic presentation; Acute myocardial infarction; Troponin; Statin therapy; Microvascular obstruction; OMI/NOMI

Core Tip: This response emphasizes that angiographic occlusion status is a strong independent prognostic marker in acute myocardial infarction (AMI), providing information beyond electrocardiographic classification and peak troponin levels. The persistent independent association with mortality suggests mechanisms beyond infarct size alone—including microvascular dysfunction and no-reflow—warranting investigation as hypotheses in future prospective studies. The association between chronic statin therapy and lower likelihood of total occlusion may reflect plaque-stabilizing effects, though requiring prospective validation. These findings support the emerging OMI/NOMI paradigm as superior to traditional electrocardiography-based AMI classification for risk stratification.

TO THE EDITOR

The electrocardiogram has traditionally guided acute myocardial infarction (AMI) triage through ST-elevation myocardial infarction (STEMI)/non-STEMI (NSTEMI) classification[1]. Our prospective cohort study of 2483 AMI patients demonstrated that angiographic occlusion status provides independent prognostic information beyond electrocardiography (ECG) presentation[1]. Singh and Lima's commentary[2] published in World Journal of Cardiology raises important points regarding the relative weight of angiographic vs electrocardiographic stratification, biomarker interpretation, and the emerging OMI/NOMI paradigm. This response addresses these substantive issues within the evolving literature on AMI phenotyping.

Background

In our cohort, 67.9% of 2483 AMI patients had occluded infarct-related artery (OCA), including 35.5% of NSTEMI patients[1]. After multivariable adjustment, ECG presentation (STEMI vs NSTEMI) was not an independent mortality predictor (HR = 1.04; 95%CI: 0.57-1.91; P = 0.899; table 4)[1], whereas total culprit-vessel occlusion tripled 30-day mortality risk (HR = 3.04; 95%CI: 1.45-6.34; P = 0.003; table 4)[1]. Peak troponin I was higher in OCA patients (20315 ng/L vs 5500 ng/L; P < 0.001; table 2)[1]. Chronic pre-admission statin therapy was independently associated with lower OCA likelihood (OR = 0.577; 95%CI: 0.367-0.906; P = 0.017; table 3)[1].

Prognostic significance of culprit-artery occlusion

The lack of independent prognostic value of STEMI vs NSTEMI after occlusion adjustment is clinically significant[1]. OCA patients were younger with fewer comorbidities, yet presented with greater hemodynamic instability: Lower systolic blood pressure (130 mmHg vs 140 mmHg), higher cardiogenic shock rates (6.5% vs 2.5%), out-of-hospital cardiac arrest (3.7% vs 1.5%), and lower post-percutaneous coronary intervention (PCI) Thrombolysis In Myocardial Infarction 3 flow (77.6% vs 86.1%)[1]. This phenotype—younger patients with acute thrombus on minimally calcified plaques—differs fundamentally from patent vessels in older patients with diffuse calcified disease[3,4]. The OMI/NOMI paradigm may better capture underlying biology and prognosis than traditional ECG classification[2].

Troponin as surrogate and mechanisms beyond infarct size

Singh and Lima[2] correctly note that troponin kinetics are influenced by timing, reperfusion efficacy, and baseline left ventricular mass[5]. Importantly, occlusion remained an independent mortality predictor after adjustment for peak troponin (table 4)[1], suggesting prognostic information beyond infarct size. Potential mechanisms—microvascular obstruction, no-reflow, heightened arrhythmic risk—remain inferential and warrant investigation as hypotheses in prospective studies[6,7]. Imaging-based infarct-size assessment [cardiac magnetic resonance imaging (MRI)] would be superior to troponin alone[8].

Prior statin therapy and plaque stabilization

The association between chronic statin use and lower OCA likelihood is notable[1]. Ndrepepa et al[9] similarly reported that prior statin use shifts presentation toward NSTEMI; our findings extend this to the OCA vs patent vessel distinction, suggesting statins may prevent acute total occlusion. However, important limitations apply: Statin intensity, duration, lipid levels, and adherence were not quantified[1]. Prior statin therapy was not an independent mortality predictor (HR = 1.35; 95%CI: 0.74-2.48; P = 0.330; table 4)[1]—likely because universal high-intensity statin therapy after PCI and confounding by higher SYNTAX scores in statin-treated patients attenuated mortality differences[10]. These are post hoc interpretations requiring prospective validation[1].

Clinical implications

Integration of angiographic occlusion status into risk stratification could refine triage[2]. NSTEMI patients with features suggestive of occluded infarct-related artery—younger age, hemodynamic instability, refractory chest pain, subtle ECG changes in posterior leads or aVR elevation—warrant expedited angiographic evaluation[1,2]. Such an approach, if validated prospectively, could reduce time to revascularization[2]. However, translation of observational findings into practice requires prospective evidence that OMI-guided triage improves outcomes compared to standard ECG-based approaches.

Limitations

This single-center observational study has inherent limitations. Left ventricular ejection fraction data were unavailable for many transferred patients. Patient medication adherence was not verified. The study period (2011-2018) encompassed significant changes in PCI practice, antithrombotic therapy, and troponin assays, which may have influenced occlusion prevalence and mortality. Angiography timing was not standardized; the 35.5% OCA prevalence in NSTEMI reflects those undergoing angiography, and selection bias cannot be excluded. Statin associations are observational and do not establish causality.

Future directions

Randomized trials comparing OMI-guided vs ECG-guided triage are warranted[2,11]. Such trials should include standardized ECG adjudication, angiography timing documentation, imaging-based infarct size assessment (cardiac MRI)[8], and endpoints including mortality, heart failure, cardiogenic shock, and infarct size by CMR. Mechanistic studies should investigate whether statins reduce total occlusion incidence[9] and whether biomarker combinations can predict angiographic occlusion pre-angiography[5].

CONCLUSIONS

Our findings reinforce that angiographic assessment of infarct-related artery patency should be integrated into AMI risk stratification[1,2]. Occlusion status provides independent prognostic information not captured by ECG classification[1]. The distinct clinical phenotypes of OCA and patent vessel patients suggest fundamentally different pathophysiological substrates[3,4]. Prospective validation of OMI-guided triage strategies and mechanistic investigation of plaque phenotyping and statin effects are essential next steps[2].