Enhanced Adhesion Molecules are Early Inflammatory Driver in Symptomatic Patients with Preserved Ejection Fraction Prior to Diastolic Dysfunction

Author(s): Carlos Plappert, Henrike Arfsten, Jan- Niklas Dahmen, Anna Feuerstein, Veronika Zach, Heinz-Peter Schultheiss, Frank Edelmann, Felicitas Escher

Background: Patients with diastolic dysfunction exhibit signs of chronic myocardial inflammation. However, which inflammatory markers are crucial in the early inflammatory process in symptomatic patients with preserved ejection fraction leading to the development of diastolic dysfunction remain elusive.

Methods: We retrospectively analyzed n=72 (49 male/23 female) consecutive patients with heart failure symptoms according to the New York Heart Association (NYHA) classification stages II-IV. Only patients with preserved left ventricular ejection fraction (LVEF) > 50% and without echocardiographic findings of diastolic dysfunction including E/e’ < 14 or left atrial volume index (LAVI) < 34 ml/m2 were enrolled. All patients underwent endomyocardial biopsies (EMBs).

Results: The mean LVEF was 58±2%. According to EMBs, immunohistological signs of inflammatory processes were shown in n=29 (40%) patients. In univariable regression analysis, age (OR: 1.410, 95% CI: 1.040-1.751, p <0.001) and adhesion molecules ICAM-1 (OR: 1.395, 95% CI: 1.029-1.780, p <0.05) were significantly associated with E/e’ in patients with microvascular inflammatory processes, respectively. The association of age and ICAM-1 with E/e’ remained virtually unchanged after adjustment for both variables. In contrast, in patients without inflammatory processes, we observed in univariable regression analysis, age (OR: 1.619, 95% CI: 1.430-1.951, p <0.001), female sex (OR: 1.449, 95% CI: 1.164-1.733, p <0.05) and low-grade CD11+cells (OR: 1.548, 95% CI: 1.273-1.823, p <0.05) were significantly associated with E/e’. After multivariable regression analysis, age (OR: 1.597, 95% CI: 1.337- 1.856, p <0.001) remained significant.

Conclusion: ICAM-1 is a key marker in the early inflammatory processes of symptomatic patients with preserved ejection fraction that are prior to diastolic dysfunction.