Introduction Myocardial infarct pathologies, including intramyocardial haemorrhage (IMH) and microvascular obstruction (MVO) are complex dynamic traits affecting around half of all survivors of acute ST-elevation myocardial infarction (STEMI). We aimed to characterise the evolution and inter-relationships between IMH and MVO in STEMI survivors to inform and implement novel therapeutic interventions.
Methods We undertook a single centre cohort study in 288 reperfused STEMI patients treated by emergency PCI (BHF MR-MI study; NCT02072850). IMR, a prognostically validated invasive microcirculatory biomarker, was measured acutely at the end of PCI using guide-wire based-thermodilution. IMH (T2* value <20 ms) and MVO were delineated as a hypointense on T2* mapping and CE-CMR, respectively, 2 days and 6 months post-MI. Time-course CMR: 30 patients underwent serial CMR at 4 time-points: 4 to 12 h, 3 days, 10 days and 6–7 months post reperfusion. Adverse remodelling was defined as an increase in left ventricular end-diastolic volume (LVEDV) ≥20% at 6 months. All-cause death or heart failure (ACD/HF) was independently assessed during follow-up. A randomised proof-of-concept clinical trial of deferred PCI vs. immediate stenting was implemented for treatment stratification.
Results The median IMR [IQR] post-PCI was 24 [15–44] (n = 288). 245 STEMI patients (86%) had evaluable T2*-CMR and 101 patients (41%) had IMH. All of the patients with IMH had MVO, but 32 patients had MVO (13%) without IMH. IMR was higher in patients with IMH (37 [21–63]) than in patients without IMH (17 [12–33]).
Using ROC analysis, the optimal cut-off for IMR in predicting IMH was 27 [AUC 0.73 (0.66, 0.79)]. The IMR cut-off of for MVO was 23.5 [AUC 0.68 (0.61, 0.75)]. IMR was more strongly associated with IMH (odds ratio 4.24 (2.38, 7.58); p < 0.001), than for MVO (2.84 (1.70, 4.73); p < 0.001).
IMR was independently associated with adverse remodelling (1.01 (1.00, 1.03); p = 0.006) and NT-proBNP at 6 months (4.64 (2.17, 7.12); p < 0.001). IMR was an associate of ACD/HF (n = 30 events during admission and post-discharge (1.016 (1.009, 1.023); p < 0.001).
Serial CMR (n = 30): IMH occurred in 7 (23%), 13 (43%), 11 (33%), and 4 (13%) patients at 4–12 h, 3 days, 10 days and 7 months, respectively. The amount of MVO was greatest 4–12 h post-reperfusion, then fell progressively over time. In contrast, the amount of IMH increased dynamically from 4–12 h with a peak at 3 days then a decrease at 10 days. MVO resolved by day 10 in 8 patients (44%), 2 (25%) of whom had evidence of IMH. Whereas MVO persisted in 10 patients (56%), all (100%) of whom had evidence of IMH.
IMR values in the highest tertile were associated with all cause death or heart failure hospitalisation (HR 3.30 (1.59, 6.86); p = 0.001) (censor time 839 (598 to 1099) days). IMH was associated with ACD/HF post-discharge (hazard ratio (95% CI): 12.9 (1.6, 100.8); p = 0.015).
In a proof-of-concept pilot trial, of 411 consecutive STEMI patients, 101 were randomised (March–Nov 2012). Compared with standard care with immediate stenting (n = 49), brief (median 9 (6–12) hours) deferral of stenting following reperfusion (n = 52) tended to reduce IMH and MVO and increased myocardial salvage.
Conclusion IMH and MVO follow divergent time-courses. IMR is strongly associated with IMH which is indicative of severe MI. IMR has potential to stratify patients acutely and deferred PCI is a simple intervention that could be implemented worldwide, if a planned Phase 3 trial confirms the hypothesis.
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