Transcardiac gradients of pro-cholecystokinin, cholecystokinin, and gastrin in patients with and without heart failure with reduced ejection fraction

Abstract

Background: Cholecystokinin (CCK) is secreted from the intestines in response to food intake. We previously reported that the CCK gene is also expressed in the mammalian heart, and it has been hypothesized that proCCK could be a novel cardiac biomarker. However, it is not known whether cardiac gene expression leads to secretion in humans. Purpose: To investigate myocardial secretion of proCCK in patients with heart failure with reduced ejection fraction (HFrEF) or arrythmias. Methods: A total of 115 patients undergoing invasive cardiac procedures were included: 55 with HFrEF (67 years [interquartile range (IQR) 60–76], 72.7 % male, LVEF 30 % [IQR 20–35]), and 60 without HFrEF (26 with Wolff-Parkinson-White syndrome (WPW) (30 years [IQR 26–39], 61.5 % male), and 34 with atrial fibrillation (AFIB) (66 years [IQR 60–71], 61.8 % male)). Blood was collected from the coronary sinus (CS) as well as the left atrium or femoral artery (A) to determine the transcardiac concentration gradient (TCproCCK) (CS proCCK concentration - A proCCK concentration). Radioimmunoassays were used for measurements of plasma hormones. Results: TCproCCK across failing hearts was 0.05 pmol/l (IQR: −1.49–2.67) (p = 0.365). In non-failing hearts, TCproCCK was 0.35 pmol/l (IQR: −1.57–1.29) (p = 0.778) for WPW and 0.68 pmol/l (IQR: −1.58–3.28) (p = 0.133) for AFIB. Transcardiac gradients for N-terminal pro B-type natriuretic peptide (NT-proBNP) were observed in all groups. Conclusions: No evidence of net myocardial secretion of proCCK was found in either failing or structurally normal hearts, questioning its proposed role as a cardiac biomarker.