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A Evolution and Inter-Relationships of Infarct Characteristics in Reperfused STEMI Survivors and Stratification for Novel Therapeutic Interventions
  1. David Carrick
  1. BHF Centre of Research Excellence, University of Glasgow, Golden Jubilee National Hospital, Glasgow

Abstract

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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