Analysis of Circulating Biomarkers in Predicting Response to Cardiac Resynchronization Therapy (CRT) With Biventricular Pacing in Patients With Congestive Heart Failure (BIOCRT)

Cardiac resynchronization therapy (CRT) with biventricular pacing has emerged as a novel treatment for congestive heart failure (CHF) not responsive to optimal drug therapy. CRT is associated with significant improvements in hemodynamics and functional status of patients with CHF. The physiologic effect of CRT is achieved via placing electrical leads in the right and left ventricular walls, and synchronizing ventricular contraction. Over time, this leads to ventricular wall reverse remodeling, and sustained improvements in left ventricular ejection fraction (EF).

Currently, the indications for CRT include end-stage heart failure class II-IV with an EF < 35%, and a QRS duration > 120ms. The QRS duration is used as an indicator of the degree of ventricular electromechanical dyssynchrony, however, a growing number of studies have postulated its inability to predict response to therapy. As a result, other measures of mechanical dyssynchrony are being sought to guide therapy. The vast majority of these studies have examined clinical, cardiac, electrocardiographic, and device-specific indices, however, a widely accepted predictor of response to CRT is lacking.

CRT results in electromechanical synchrony, leading to an improved ejection fraction, exercise tolerance, and reduction of symptoms. Although electrical re-synchronization and intra-procedural hemodynamic improvement are achieved after the device is implanted, the sustained clinical improvement is likely due to ventricular reverse remodeling. A major issue with CRT is that approximately a third of patients receiving devices do not achieve improved clinical or functional status, and fail to undergo changes in ventricular geometry, and ventricular remodeling. It remains unknown whether this is due to abnormalities in the factors involved in lead placement or procedural strategies, geometric remodeling, alterations in cardiac energy metabolism, supply of energy (i.e. coronary blood flow), or inappropriate/inadequate microvascular proliferation.

This study will evaluate a series of biochemical markers implicated in pathophysiology of heart failure, in predicting response to CRT with biventricular pacing.