Association between Dual-chamber (DDD) Pacemakers and Plasma Level of Soluble Suppression of Tumorigenicity-2 (sST2). A Case-Control Study in a Sample of Iraqi Patients

Abstract

Abstract

Dual-chamber pacemakers are well recognized for having a close physiological resemblance to the cardiac sequence of chamber activation. Yet, they can import a negative impact on the cardiac function as a result of the inevitable dyssynchrony caused by right ventricular pacing which eventually may affect the left ventricular function through remodelling.

Soluble suppression of tumorigenicity-2  (sST2) is one of the two isoforms for the ST2 that circulates as a protein in contrast to a second isoform called transmembrane ST2 (ST2L) which is cell bound transmembrane receptor expressed by a variety of cells including cardiomoycytes. After a cardiac insult, IL-33 acts as a ligand for ST2L that upon binding, will counteract the adverse effects of cardiac remodeling and fibrosis resultant from that insult and thus limiting insult`s extent. sST2 expresses itself as an alternative (decoy) receptor for IL-33 competing with ST2L preventing it from binding to IL-33, therefore, the cardioprotective measures of ST2L/IL33 will be compromised.

Objective: sST2 expresses an elevated levels in association with different cardiovascular diseases such as heart failure, pulmonary hypertension and myocardial infarction. This study aimed to investigate the effect of dual-chamber pacemaker on sST2 levels in patients with preserved ejection fraction.

Methods: a case-control study included 52 patients with dual-chamber pacemakers, 38 (68%) of them were males, together with gender and age matched controls were selected. Participants were divided into patients and control groups. Exclusion criteria were heart failure, recent acute coronary syndrome (ACS), uncontrolled hypertension, left ventricular hypertrophy (LVH), uncontrolled diabetes, pulmonary hypertension, right bundle branch block (RBBB), and atrial fibrillation. Plasma level of sST2 was measured for each participant alongside ECG and TTE to calculate the EF%, CO, SV, LVPEP, and RVPEP.

Results: sST2 was significantly higher in patient group (p = 0.0001), 95% CI [18.06, 25.22]. Patients also recorded a significantly lower values of EF%, CO, and HR (p = 0.0001). As a measure of inter-ventricular dyssynchrony, ΔVPEP was significantly higher in patients group (p = 0.0001), 95% CI [18.06, 25.22]. The results didn’t show statistically significant difference in SV (p = 0.3399) and RVPEP (p = 0.6197) between patients and controls.

Conclusion: dual-chamber pacemakers are associated with elevated sST2 levels through inducing an electromechanical cardiac dyssynchrony that culminate into left ventricular remodeling and minor fibrosis.

Key words: sST2, Dual-chamber pacemaker, Dyssynchrony, Echocardiography, Remodelling.