Molecular Imaging of Systemic Inflammatory Response in Lymphatic Organs Provides Prognostic Value after Re-Perfused Acute Myocardial Infarction
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
Acute myocardial infarction (AMI) triggers local inflammation in the injured myocardium, followed by a systemic inflammatory response of lymphatic organs. This prospective trial investigated whether molecular imaging of lymphatic organs (spleen, bone marrow, and heart-draining lymph nodes (LN)) identifies individuals predisposed to functional recovery during follow-up after AMI.
Methods
41 timely re-perfused ST-elevation AMI patients received positron emission tomography (PET) using 68 Ga-PentixaFor, a radiotracer targeting C-X-C motif chemokine receptor 4 (CXCR4) post-AMI. Patients were allocated to an early (2-4 days) or late PET imaging group (5-8 d) based on tracer availability. To determine left ventricular ejection fraction (LVEF) and infarct size, cardiac magnetic resonance imaging was conducted at baseline and repeated after six (follow-up (FU) 1, available in 38/41) and twelve months (FU 2, 36/41). As endpoint, an LVEF increase of ≥5% relative to baseline was then defined as short- (at FU 1) and long-term functional (at FU 2) recovery. We also determined association of 68 Ga-PentixaFor uptake in the infarct territory and lymphatic organs with outcome relative to established clinical and imaging biomarkers.
Results
At FU 1, functional recovery was recorded in 21/38 patients. Univariate analysis identified baseline LVEF (Odds Ratio (OR), 0.80, P=0.002) and uptake derived from heart-draining LN (OR, 0.21, P=0.03) as predictor of functional recovery, while only LVEF reached significance at multivariate analysis (OR, 0.72, P=0.007). At FU 2, functional recovery was observed in 21/36 patients and LVEF (OR, 0.84, P=0.005) and splenic PET signal (OR, 2.46, P=0.04) provided prognostic value at univariate analysis. Both parameters remained significant at multivariate outcome analysis (LVEF: OR, 0.73, P=0.01; spleen: OR, 4.17, P=0.04), indicating that low baseline LVEF and high splenic tracer uptake are prognostic for improved long-term functional outcome. Established risk factors of cardiac damage (infarct size) or inflammation (C-reactive protein, white blood cell counts) failed to reach significance for functional recovery at FU 1 and FU 2.
Conclusions
Along with baseline EF, imaging of chemokine receptor expression in the spleen provides a complementary in-vivo biomarker for long-term functional recovery. Whole-body PET-based assessment of systemic inflammatory response in lymphatic organs may therefore open avenues for immune modulation strategies in patients after AMI.
