The prospective study aims:

1. To determine the role and mechanism of biomarkers for prediction of response to CRT
2. To determine the role of biomarkers and their effect on left ventricular remodeling in patients undergoing CRT.

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.

Inclusion Criteria:

• Study participant with an approved indication for a CRT or CRT-D system.

  1. New York Heart Association (NYHA) Class II, III, or IV Heart Failure unresponsive to drug therapy.
  2. EF < 35%.
  3. QRS width > 120 ms.

• Study participant receiving optimal medical therapy including ACE inhibitor or Angiotensin Receptor Blocker (ARB), Beta-Blocker, and Diuretic.

• Study participants with a history of significant congestive decompensation events within the last 12 months.

Exclusion Criteria:

• NYHA Class I Heart Failure.
• Co morbidities (e.g., cancer), which may limit lifespan < 6 months.
• Severe aortic stenosis (valve area < 1.0 cm2).
• Study participants that received cardiac surgery or intervention (i.e. coronary artery bypass grafting (CABG), valve surgery, angioplasty, arthrectomy) within the preceding 90 days.
• Study participants with moderate to severe chronic obstructive pulmonary disease (COPD), defined as needing chronic oxygen therapy or recent hospitalization (within 30 days) for COPD flare up.
• Concurrent pregnancy.
• Study participants with primary pulmonary hypertension.
• Study participants on continuous or intermittent infusion therapy for heart failure.

Outpatient or inpatient heart failure patients scheduled for CRT implantation