CXCR4 PET/CT Predicts Left Ventricular Recovery 8 Months After Acute Myocardial Infarction

Acute myocardial infarction (AMI) triggers an inflammatory response, which is a determinant of subsequent healing. We speculated that C-X-C motif chemokine receptor 4 (CXCR4) upregulation early after AMI predicts left ventricular (LV) remodeling and cardiac structural functional outcome. Methods: In total, 49 patients underwent multimodal cardiac imaging including PET with the specific CXCR4 ligand ⁶⁸Ga-pentixafor, myocardial perfusion imaging, and cardiac MR (CMR) within the first week after AMI. Follow-up CMR was acquired after 8.3 ± 4.2 mo in 40 patients. Results: Initial PET-derived CXCR4 expression in the infarct territory was significantly higher than blood pool (SUV_peak, 2.5 ± 0.5 vs. 2.0 ± 0.3; P < 0.001) but had high variance (1.5–4.2) among patients. The calculated area of CXCR4 upregulation (CXCR4 area, median 27.0% of LV; interquartile range [IQR], 11.0%–42.0%) was significantly larger than perfusion defect size (median 18% of LV; IQR, 3.0%–33.5%; P = 0.043) but not larger than the late gadolinium enhancement (LGE) extent in initial CMR (median 23.6% of LV; IQR, 18.2–30.3; P = 0.382). Myocardial CXCR4 area correlated with initial LV ejection fraction (LV-EF) (r = −0.533, P < 0.001), follow-up LV-EF (r = −0.420, P = 0.005), and initial LGE extent reflecting the area of myocardial injury (r = 0.559, P < 0.001). No correlation was found with LGE extent at follow-up. We investigated the association of baseline ⁶⁸Ga-pentixafor uptake with functional outcome derived from follow-up CMR to established markers of myocardial damage. At 8-mo follow-up, a significant improvement in LV-EF (46.5 ± 10.3% vs. 49.1% ± 10.4%, P = 0.049) was noted, and the extent of LGE (% of LV) decreased (median 23.6% vs. 16.9% of LV; P < 0.001). The CXCR4 area emerged as an independent predictor of follow-up LV-EF (P = 0.049), outperforming baseline LGE extent (P = 0.318); however, its prognostic value diminished when accounting for initial perfusion defect, suggesting overlapping pathophysiologic information. Conclusion: CXCR4-targeted molecular imaging early after AMI bears potential to predict subsequent ventricular remodeling and may be a useful clinical tool for risk stratification and guidance of antiinflammatory therapies.