Baseline White Blood Cell Count Predicts Infarct Size in Anterior STEMI

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Among patients with anterior ST-segment elevation myocardial infarction (STEMI), elevated white blood cell (WBC) count at baseline is a powerful independent predictor of infarct size as measured by cardiac magnetic resonance imaging (MRI), according to a substudy of the INFUSE-AMI trial published online September 23, 2013, ahead of print in the American Journal of Cardiology.

For the INFUSE-AMI trial, published in the Journal of the American Medical Association, researchers randomized 452 STEMI patients with large, anterior infarcts to primary PCI plus bivalirudin anticoagulation with or without a bolus (0.25 mg/kg) of abciximab. Patients were also randomized to treatment with or without manual aspiration thrombectomy. While abciximab reduced infarct size, manual aspiration thrombectomy did not.

The substudy, led by Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), evaluated the 407 subjects from the main cohort with available WBC counts at admission. These patients were stratified into tertiles based on WBC count:

• Tertile 1: < 9,700/mm³ (n = 135)
• Tertile 2: 9,700-13,199/mm³ (n = 133)
• Tertile 3: ≥ 13,200/mm³ (n = 139)

Infarct Size Rises with WBC Count

Cardiac MRI was available in 82.3% (n = 335) of patients at 30 days. There was a stepwise increase in median infarct size as a percentage of total LV mass (primary endpoint) across the patient tertiles, with similar patterns seen in absolute infarct mass, LV end-systolic and -diastolic volumes, and total abnormal motion score. In addition, LVEF decreased across the tertiles (table 1).

Table 1. Cardiac MRI Results at 30 Days by WBC Tertile

 
After adjustment, WBC count independently predicted infarct size (P = 0.0001), as did age, intracoronary abciximab randomization, total ischemic time, proximal LAD location, and baseline TIMI 0/1 flow. There was no interaction between WBC count and abciximab with regard to infarct size (P = 0.30).

At 30 days, mortality was more than threefold higher, and TIMI major bleeding was more than twofold greater in the upper tertile of WBC count than in the other tertiles, although in neither case did the difference reach statistical significance. All deaths were cardiac. On the other hand, rates of reinfarction, TVR, and stent thrombosis did not vary according to tertile (table 2).

Table 2. Kaplan-Meier Outcomes at 30 Days

 
Causality Remains to Be Proven

“By enrolling only patients with anterior STEMI and proximal or mid-LAD occlusion and determining infarct size with [cardiac] MRI 30 days after primary PCI, our study overcomes several limitations of previous studies and reliably assesses the relation between [WBC count] and infarct size in this particular setting,” Dr. Stone and colleagues write. “Moreover, the large number of clinical, angiographic, and procedural variables collected in the INFUSE AMI trial made it possible to correct for several confounders known to affect infarct size.”

The substudy does not prove causality, the authors acknowledge, suggesting several mechanisms to explain how WBCs may impact infarct size. These cells:

• Potentially contribute to oxidative and proteolytic myocardial injuries
• May have prothrombotic properties by producing tissue factor, providing a catalyst for thrombin generation
• Can cause rheological compromise of the microvasculature by several means

“More specific studies are required to address the possible causal relation between an elevated [WBC count] and infarct size,” they observe. “In contrast, it is also possible that greater [WBC count] on presentation represents an early inflammatory response to ongoing larger myocardial injury.”

Although not powered to detect significant differences in mortality, the substudy importantly suggests substantially higher death rates among patients in tertile 3, the authors note, consistent with prior research. “By showing that [WBC count] is an independent predictor of infarct size, we suggest a possible mechanistic link between WBC and cardiac mortality,” they write.

Study Details

Patients in tertile 3 were younger and more likely to be smokers, and they had longer ischemic time and lower LVEF at hospital admission compared with patients in the other 2 tertiles. They were also more likely to present with TIMI 0 flow, thrombus-containing lesions, greater thrombus area, and greater extent of ST-segment elevation.

Note: Dr. Stone and several coauthors are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

 

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Source:
Palmerini T, Brener SJ, Généreux P, et al. Relation between white blood cell count and final infarct size in patients with ST-segment elevation acute myocardial infarction undergoing primary percutaneous coronary intervention (from the INFUSE AMI trial). Am J Cardiol. 2013;Epub ahead of print.

 

 

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