CMR-Backed Troponin-Based CCS-AMI Staging of Myocardial Injury in Reperfused STEMI Patients: Clinical Focus on Hemorrhagic MI

Background: Canadian Cardiovascular Society Staging of Acute Myocardial Infarction (CCS-AMI) can be used to stage myocardial tissue injury in reperfused infarctions with CMR and inform patient prognosis: Stage I - aborted MI (edema only), Stage II (edema with necrosis), Stage III (edema, necrosis and microvascular obstruction), Stage IV (tissue injuries of Stage III + intramyocardial hemorrhage). Universal CMR for all patients with acute myocardial infarction remains infeasible. A fast, inexpensive blood-based triage that reliably identifies CCS stage of injury and selective deployment of CMR in reperfused MI patients.

Methods: We studied 267 consecutive reperfused acute MI patients and staged them according to CCS-AMI criteria for determination of edema by T2-based techniques, necrosis by late gadolinium enhancement (LGE), MVO as persistent hypoenhancement within LGE, and IMH by T2* hypointensity. High-sensitivity cardiac troponin-I (hs-cTn-I) was sampled serially at −1 h (pre-PCI), 0 h (immediately post-reperfusion), and hourly up to 11 hours. Peak hs-cTn-I was defined as the maximum [hs-cTn-I] observed within the first 12 hours and was used to assess the relationship with CCS-AMI stages. Diagnostic performance was assessed using Receiver Operating Characteristic (ROC) curve analysis to determine the Area Under the Curve (AUC). Optimal thresholds for differentiating clinically CCS-AMI stages were determined using Youden's J statistic along with sensitivity and specificity measures.

Results: Peak [hs-cTn-I] levels demonstrated a clear stepwise increase with severity of tissue injury as determined with CMR. The median (IQR) peak hs-cTn-I values (in ng/ml were 9.0 (2.2–18.2) for Stage I, 39.1 (14.4–82.8) for Stage II, 73.3 (31.1–127.9) for Stage III, and 210.9 (115.9–415.1) for Stage IV (Fig 1). At [hs-cTn-I] > 62.3 ng/ml effectively separated patients with at Stage III or greater from those with Stage II injury: sensitivity of 81.7% and specificity of 71.7% (AUC 0.839). Importantly, a peak [hs-cTn-I] level >156.6 ng/ml identified those with Stage IV injury (compared to those with Stage III injury): sensitivity of 65.8%, specificity of 90.0% and AUC of 0.841 (Fig. 2).

Conclusion: Post-reperfusion high-sensitivity cardiac troponin has the potential to enable CCS staging of myocardial injury in reperfused STEMI patients. While this remains to be validated in broader patient populations, our early findings demonstrate that STEMI patients can be triaged for value-based CMR and for clinical trials aimed at developing therapeutic interventions targeting the stage of tissue injury.

Figure 1. CMR-backed Staging of CCS-AMI with [hs-cTn-I] Kinetics. Left panel shows representative CMR images from CCS-AMI Stages I–IV. T2-weighted, LGE, and T2* images are displayed for each stage, with endocardial (red) and epicardial (green) contours delineating left-ventricular myocardium. CCS I represents early ischemic injury with edema, CCS II shows tissue necrosis without microvascular obstruction, CCS III demonstrates necrosis with microvascular obstruction, and CCS IV is characterized by intramyocardial hemorrhage in addition to stage III tissue injury.
Figure 2. Blood Marker Based Diagnosis of CCS-AMI Stage of Tissue injury ROC curves demonstrate the discriminatory ability of high-sensitivity cardiac troponin I concentration ([hs-cTn-I]) in differentiating CCS-AMI stages. Left panel shows diagnostic performance at peak [hs-cTn-I], with areas under the curve (AUC) of 0.821 for Stage I vs. Stages II–IV, 0.848 for Stage II vs. Stages III–IV, and 0.887 for Stage III vs. Stage IV. Right Panel shows [hs-cTn-I] measurements at 3 hours post-PCI, yielding AUC values of 0.806, 0.836, and 0.876 for the same stage comparisons, respectively. The high AUC values demonstrate robust diagnostic performance, with earlier post-PCI measurements closely approximating the discriminatory accuracy of peak [hs-cTn-I] values.