Molecular imaging of lymphatic organs provides prognostic value after acute myocardial infarction

Abstract Introduction Acute myocardial infarction (AMI) triggers local inflammation in the injured myocardium, followed by a systemic inflammatory response of lymphatic organs. This prospective trial (NCT05519735) focused on molecular imaging of lymphatic organs (spleen, bone marrow, and heart-draining lymph nodes) and aimed to determine whether uptake in such remote organs identifies individuals predisposed to functional recovery during follow-up after AMI. Methods 41 timely re-perfused ST-elevation AMI patients received baseline C-X-C motif chemokine receptor 4 directed 68 Ga-PentixaFor PET, a radiotracer targeting a broad spectrum of leukocytes. 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, available in 36/41). As endpoint, an LVEF increase of ≥ 5% relative to baseline was defined as short- (at FU 1) and long-term functional (at FU 2) recovery. We also determined association of 68 Ga-PentixaFor uptake in lymphatic organs with outcome relative to established clinical and imaging biomarkers. Results LVEF at baseline was 50.4 ± 8.7% (range 34–65%). At FU 1, LVEF improved significantly (54.2 ± 7.1%, P = 0.0004 vs. baseline) and the endpoint 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 lymph nodes (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, LVEF also improved to 54.3 ± 7.3% relative to baseline ( P = 0.006) and the endpoint was met in 21/36 patients. Baseline 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 baseline LVEF and splenic 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 both follow-up time-points. Conclusions Inflammatory imaging in lymphatic organs may provide a complementary in-vivo biomarker for functional recovery and seems to be more strongly associated with outcome relative to standard markers of cardiac damage or inflammation.