Early blood-derived predictors of final infarct size in patients with anterior STEMI and primary PCI

Abstract Background The association between infarct size (IS), all-cause mortality, and hospitalisation for heart failure has been documented extensively. However, the gold standard for assessing IS, cardiac magnetic resonance (CMR) imaging, is inaccessible for most patients due to cost and capacity issues. Purpose Attempting to resolve this, we assessed a wide range of blood-derived biomarkers to see their correlations with final IS, which we determined by CMR at 90 days post-infarct. Methods We followed 50 patients with anterior STEMI within 5 hours of pain onset as part of the FRACTAL trial. FRACTAL was a two-armed, double-blinded and placebo-controlled study of KAND567, a CX3CR1 receptor-blocking drug candidate. We quantified a multitude of peripheral blood derived parameters at 8 time points (baseline, 5 min, 90 min, 3h, 24h, 48h, 72h, and 6 days). At each time point we analysed full blood counts, lactate dehydrogenase (LDH), liver function parameters (AST and ALT), creatine kinase (CK), NT-pro BNP, high sensitive CRP, interleukin-6, PCSK9, fractalkine (CX3CL1) and cardiac troponin T (TnT). We also used conventional multicolour flow cytometry of full blood, and spectral flow cytometry (38 antibodies) from cryopreserved mononuclear cells for deep immunophenotyping. At 90 days post-infarct we used CMR with gadolinium contrast to visualise and quantify IS by the GAD ±5SD method (range 3.4-84.4 g). Results The biomarker we found with the strongest correlation (Spearman’s rank test) with IS was LDH at 24h (r= 0.87, p0.001, see figure), closely followed by LDH at 72h (r= 0.73, p0.001). Liver function parameters at 24h also showed strong correlation; AST (r= 0.72, p0.001) and ALT (r= 0.71, p0.001), followed by TnT at 24h (r= 0.70, p0.01), CK at 24h (r=0.67, p0.001) and interleukin-6 at 24h (r=0.53, p0.001). The strongest immune cell parameter correlations with IS were intermediate monocytes (C14+CD16+) at 24h (r=0.49, p0.001) and neutrophils at 72h (r=0.56, p0.001). Interestingly, correlation between IS and left ventricular ejection fraction (LVEF) at 90 days was only r=-0.61 (p0.001). Conclusion Cardiac specific troponin is the most sensitive biomarker used to exclude myocardial damage in patients with acute chest pain, and is also often used to estimate IS in patients post STEMI. However, our study results suggest that there are better parameters to estimate final IS, most importantly LDH at 24h. Whilst LDH has an inferior specificity to TnT, its 5-times longer half-life may explain its superiority when predicting IS. Hence, there is great potential for LDH to be used as a surrogate end point in clinical trials and in clinical routine as a predictor of future adverse cardiac outcomes.Correlation between LDH at 24h and IS