Abstract 18422: Plasma Notch Ligand Dll1 is Associated With Symptom Severity and Diastolic Dysfunction in Dilated Cardiomyopathy

Introduction: In idiopathic dilated cardiomyopathy (IDC), left ventricular dilation is caused by myocardial remodeling, to which inflammation, fibrosis and changes in the extracellular matrix composition contribute. The subprocesses may involve Notch signaling. Circulating Notch ligand Delta-like-1 (DLL1) is elevated in chronic heart failure (HF). Hypothesis: We hypothesized that in IDC, circulating DLL1 would correlate to clinical and hemodynamic variables. Methods: We measured plasma DLL1 in a prospectively recruited cohort of 102 patients with IDC, left ventricular end diastolic internal diameter ≥6.5 cm and ejection fraction ≤40% and in 32 age- and sex-matched healthy controls. Results: The study population had a median DLL1 of 11.3 ng/mL (interquartile range 9.7, 13.2). DLL1 was higher in patients in NYHA class III/IV compared to controls and NYHA class I/II (Figure 1A). Survival was poorer in patients with high DLL1 plasma levels (Figure 1B). DLL1 correlated with N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), White blood cell count (WBC) and Troponin T (TnT), and modestly with echocardiographic indicators of diastolic dysfunction (DD) (Table 1). Particularly high DLL1 levels were observed in patients with severe HF (i.e. NYHAIII/IV) and high E/e’ or E/A ratios (Figure 1C). Conclusions: Plasma DLL1 is elevated in IDC and correlates with neurohormonal activation, inflammation and adverse outcome. Levels are particularly high in patients with severe HF and DD. Notch signaling may have a role in severe HF caused by IDC.