Aims
Growth differentiation factor‐15 (GDF‐15) is a stress‐responsive cytokine and is emerging as a biomarker of cardiac remodelling. Left ventricular assist devices (LVADs) provide unloading of the left ventricle, resulting in partial reverse remodelling. Our aim was to study GDF‐15 in patients with a non‐ischaemic dilated cardiomyopathy (DCM) during LVAD support.
Methods and results
We analysed circulating GDF‐15 in 30 patients before and 1, 3, and 6 months after LVAD implantation and before heart transplantation or explantation. In addition, mRNA and protein expression of GDF‐15 were evaluated in myocardial tissue obtained prior to and after LVAD support. Circulating GDF‐15 was significantly higher before LVAD implantation as compared with healthy controls (P < 0.001). After 1 month of mechanical support, GDF‐15 levels were significantly decreased compared with pre‐implantation levels (P < 0.001) and remained stable thereafter. Circulating GDF‐15 was significantly correlated with kidney function and the severity of myocardial fibrosis. Interestingly, GDF‐15 mRNA and protein expression in the myocardium were hardly detectable.
Conclusions
High circulating levels of GDF‐15 in patients with end‐stage non‐ischaemic DCM correlate with myocardial fibrosis and kidney function and decline strongly after 1 month of mechanical unloading, remaining stable thereafter. However, cardiac mRNA and protein expression of GDF‐15 are very low, suggesting that the heart is not an important source of GDF‐15 production in these patients.
In patients with suspected stable CAD, a tiered cardiac CT protocol with dynamic perfusion imaging offers a fast and efficient alternative to functional testing. (Comprehensive Cardiac CT Versus Exercise Testing in Suspected Coronary Artery Disease 2 [CRESCENT2]; NCT02291484).
cf-LVAD support is associated with lengthening of cardiomyocytes, without alterations in diameter size. Remarkably, myocardial fibrosis increased as well as circulating pro-fibrotic markers. Whether the morphological changes are a direct effect of reduced pulsatility during cf-LVAD support or due to HF progression requires further investigation.
Objective To determine the potential impact of on-site CT-derived fractional flow reserve (CT-FFR) on the diagnostic efficiency and effectiveness of coronary CT angiography (CCTA) in patients with obstructive coronary artery disease (CAD) on CCTA. Methods This observational cohort study included patients with suspected CAD who had been randomized to cardiac CT in the CRESCENT I and II trials. On-site CT-FFR was blindly performed in all patients with at least one ≥ 50% stenosis on CCTA and no exclusion criteria for CT-FFR. We retrospectively assessed the effect of adding CT-FFR to the CT protocol in patients with a stenosis ≥ 50% on CCTA in terms of diagnostic effectiveness, i.e., the number of additional tests required to determine the final diagnosis, reclassification of the initial management strategy, and invasive coronary angiography (ICA) efficiency, i.e., ICA rate without ≥ 50% CAD. Results Fifty-three patients out of the 372 patients (14%) had at least one ≥ 50% stenosis on CCTA of whom 42/53 patients (79%) had no exclusion criteria for CT-FFR. CT-FFR showed a hemodynamically significant stenosis (≤ 0.80) in 27/53 patients (51%). The availability of CT-FFR would have reduced the number of patients requiring additional testing by 57%-points compared with CCTA alone (37/53 vs. 7/53, p < 0.001). The initial management strategy would have changed for 30 patients (57%, p < 0.001). Reserving ICA for patients with a CT-FFR ≤ 0.80 would have reduced the number of ICA following CCTA by 13%-points (p = 0.016). Conclusion Implementation of on-site CT-FFR may change management and improve diagnostic efficiency and effectiveness in patients with obstructive CAD on CCTA. Key Points • The availability of on-site CT-FFR in the diagnostic evaluation of patients with obstructive CAD on CCTA would have significantly reduced the number of patients requiring additional testing compared with CCTA alone. • The implementation of on-site CT-FFR would have changed the initial management strategy significantly in the patients with obstructive CAD on CCTA. • Restricting ICA to patients with a positive CT-FFR would have significantly reduced the ICA rate in patients with obstructive CAD on CCTA.
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