Multimodal imaging identifies inflammation and fibrosis in response to pressure overload-induced heart failure and detects alleviation of cardiac remodeling following ventricular unloading

Ziel/Aim Inflammation plays a crucial role in heart failure (HF) and contributes to (myo)fibroblast activation and interstitial fibrosis. We hypothesized that non-invasive multimodality imaging would reveal parallel development of inflammation and fibrosis in pressure overload HF, which could be alleviated by mechanical unloading.

Methodik/Methods C57Bl/6 mice underwent transverse aortic constriction (TAC, n = 41) or sham surgery (n = 20). The aortic band was removed 3 wk after TAC to unload the ventricle (rTAC, n = 10). Serial PET imaging of chemokine receptor CXCR4 using Ga-68-pentixafor at 1 and 3wk after TAC and 1wk and 3wk after rTAC assessed inflammation. Cardiac magnetic resonance (CMR) measured left ventricle (LV) geometry, ejection fraction (EF) and fibrosis via T1 mapping. Autoradiography, immunohistochemistry and histology validated imaging data.

Ergebnisse/Results TAC increased LV mass (131 ± 20 vs 87 ± 7 mg, p < 0.001) and lowered ejection fraction (EF, 44 ± 12 vs 66 ± 6 %, p < 0.001) compared to sham. Failing hearts exhibited diffuse CXCR4 PET signal at 1 wk after TAC (% injected dose (ID)/g, 0.96 ± 0.20 vs 0.74 ± 0.25, p < 0.001). Early CXCR4 PET signal predicted late EF (r = − 0.42, p = 0.01). Autoradiography confirmed tracer uptake, proportional to CD68 + macrophage content. CMR T1 mapping revealed prolonged relaxation time after TAC (1151 ± 139 vs 1006 ± 34 ms, p = 0.003), which correlated with EF (r = 0.76, p < 0.001) and fibrotic area defined by histology (r = 0.69, p = 0.006). Mechanical unloading led to rapid EF recovery (57 ± 13 vs 44 ± 15 %, p = 0.022). Both CXCR4 PET signal and T1 relaxation were partially restored by rTAC compared to pre-unloading (0.75 ± 0.19, p = 0.026; 1002 ± 61, p = 0.004).

Schlussfolgerungen/Conclusions Inflammation and fibrosis occur in parallel early in pressure overload HF, which can be alleviated by ventricular unloading. CXCR4 PET and CMR T1 mapping provide sensitive monitoring of inflammation and fibrosis progression and response to mechanical therapy. Accordingly, multimodality imaging may facilitate monitoring of therapeutic intervention in HF.