Current Smoking and Prognosis After Acute ST-Segment Elevation Myocardial Infarction: New Pathophysiological Insights

Abstract

Objectives: The aim of this study was to mechanistically investigate associations among cigarette smoking, microvascular pathology, and longer term health outcomes in patients with acute ST-segment elevation myocardial infarction (MI).

Background: The pathophysiology of myocardial reperfusion injury and prognosis in smokers with acute ST-segment elevation MI is incompletely understood.

Methods: Patients were prospectively enrolled during emergency percutaneous coronary intervention. Microvascular function in the culprit artery was measured invasively. Contrast-enhanced magnetic resonance imaging (1.5-T) was performed 2 days and 6 months post-MI. Infarct size and microvascular obstruction were assessed using late gadolinium enhancement imaging. Myocardial hemorrhage was assessed with T2* mapping. Pre-specified endpoints included: 1) all-cause death or first heart failure hospitalization; and 2) cardiac death, nonfatal MI, or urgent coronary revascularization (major adverse cardiovascular events). Binary logistic regression (odds ratio [OR] with 95% confidence interval [CI]) with smoking status was used.

Results: In total, 324 patients with ST-segment elevation MI were enrolled (mean age 59 years, 73% men, 60% current smokers). Current smokers were younger (age 55 ± 11 years vs. 65 ± 10 years, p < 0.001), with fewer patients with hypertension (52 ± 27% vs. 53 ± 41%, p = 0.007). Smokers had better TIMI (Thrombolysis In Myocardial Infarction) flow grade (≥2 vs. ≤1, p = 0.024) and ST-segment resolution (none vs. partial vs. complete, p = 0.010) post-percutaneous coronary intervention. On day 1, smokers had higher circulating C-reactive protein, neutrophil, and monocyte levels. Two days post-MI, smoking independently predicted infarct zone hemorrhage (OR: 2.76; 95% CI: 1.42 to 5.37; p = 0.003). After a median follow-up period of 4 years, smoking independently predicted all-cause death or heart failure events (OR: 2.20; 95% CI: 1.07 to 4.54) and major adverse cardiovascular events (OR: 2.79; 95% CI: 2.30 to 5.99).

Conclusions: Smoking is associated with enhanced inflammation acutely, infarct-zone hemorrhage subsequently, and longer term adverse cardiac outcomes. Inflammation and irreversible myocardial hemorrhage post-MI represent mechanistic drivers for adverse long-term prognosis in smokers. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction. [BHF MR-MI]; NCT02072850).

Keywords: cigarette smoking; magnetic resonance imaging; microcirculation; myocardial hemorrhage; myocardial infarction; prognosis.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Graphical abstract

Figure 1

Smoking and Myocardial Hemorrhage After Acute ST-Segment Elevation Myocardial Infarction Current smoker (A to D) and nonsmoker (E to H) who underwent primary percutaneous coronary intervention (PCI) for lateral ST-segment elevation myocardial infarction. Both had TIMI (Thrombolysis in Myocardial Infarction) flow grade 3 post-PCI. Antithrombotic therapies, including aspirin, clopidogrel, and unfractionated heparin, were similar for both patients. Magnetic resonance imaging (MRI) was performed 2 days and 6 months later. (A to D) Imaging from a 58-year-old male current smoker. Symptom-to-balloon time was 8.5 h. Angiography revealed a proximally occluded circumflex coronary artery (yellow arrow, A). Two days later, myocardial hemorrhage was revealed by T2* mapping (white arrow, C). Late gadolinium enhancement revealed transmural infarction of the lateral left ventricular (LV) wall (white arrows, D) associated with microvascular obstruction (MVO) (yellow arrow, D). Baseline infarct size was 32.3%, LV ejection fraction 55%, and LV end-diastolic volume indexed to body surface area (LVEDVi) 83.8 ml/m2. Six months later, infarct size was 31.2% and LVEDVi 84.8ml/m2, consistent with adverse remodeling. (E to H) Imaging from a 48-year-old male nonsmoker. Symptom-to-balloon time was 9.3 h. Angiography revealed a proximally occluded circumflex coronary artery (yellow arrow, E). Two days later, there was no evidence of myocardial hemorrhage (G) or MVO within the infarct zone (H) on MRI. Baseline infarct size was 25.3%, LV ejection fraction 51%, and LVEDVi 78.4 ml/m2. Six months later, infarct size was 15.2% and LVEDVi 72.7 ml/m2.

Figure 2

Flow Diagram Consolidated Standards of Reporting Trials flow diagram of the study. CMR = cardiac magnetic resonance; MRI = magnetic resonance imaging; STEMI = ST-segment elevation myocardial infarction.

Figure 3

Smoking and Microvascular Pathology After ST-Segment Elevation Myocardial Infarction Schematic of the pathophysiology of cigarette smoking, infarct pathology, and prognosis post–acute ST-segment elevation myocardial infarction (STEMI). The results indicate that smoking is associated with accelerated vascular risk. Despite a typically successful outcome after primary percutaneous coronary intervention (PCI), microvascular pathology within the infarct zone (MVO [microvascular obstruction] and myocardial hemorrhage) is more likely, which increases the long-term risk. CAD = coronary artery disease; IMH = intramyocardial hemorrhage; MACE = major adverse cardiac events.