Congestive heart failure (CHF) is the number one hospital discharge diagnosis for older adults and the leading cause of hospital readmissions, reflecting poor quality of life for patients and increased healthcare resource use, and is the cause of 300,000 deaths annually.¹ Cardiac resynchronization therapy (CRT) has become a new effective treatment modality in those with drug-resistant advanced CHF.² Recommendations for optimal patients eligible for CRT are based on trials that showed its benefit in patients with wide QRS (?120ms), advanced left ventricular (LV) systolic dysfunction with an ejection fraction of ?35%, LV enlargement (enddiastolic diameter ?5.5cm) and class III or IV CHF symptoms despite optimum medical regimen^.3,4 Evaluation of these studies shows that as many as 30–40% of patients do not respond to or even deteriorate after CRT despite tight selection criteria.³

Several potential mechanisms may be responsible for this lack of benefit in some patients post-CRT, discussed below.

Electrical versus Mechanical Dyssynchrony

Electrical dyssynchrony as determined by electrocardiogram (ECG) may not necessarily determine mechanical dyssynchrony—the real target for correction by CRT. In support of this argument, there are a number of studies that have compared electrical with mechanical dyssynchrony criteria and found that the response to CRT is better predicted by mechanical dyssynchrony rather than by electrical dyssynchrony.⁵ The problem with these mechanical dyssynchrony criteria is that these studies have evaluated different segments of the myocardium and vary in the extent of evaluation of the myocardium, as well as in the timing of evaluation within the cardiac cycle.^6–10 This results in disparity among various dyssynchrony criteria when one compares one method with another. Intra-subject variability in these measurements of mechanical dyssynchrony is another confounder.

Mechanical dyssynchrony in the radial direction—particularly by speckle tracking—is a newer method that can improve patient selection;¹¹ however, radial dyssynchrony does not necessarily correlate with mechanical dyssynchrony in the longitudinal direction and the significance of one over the other is unclear. Other evidence in support of the importance of mechanical rather than electrical dyssynchrony is the finding of significant response to CRT in patients with narrow QRS who obviously do not have electrical synchrony—at least based on surface QRS—but nevertheless have significant mechanical dyssynchrony.^12–14

Technical Factors

Besides the presence of mechanical dyssynchrony itself, there are several technical reasons that may be responsible for lack of response from CRT.15 These include selection of inappropriate targets for resynchronization. In general, it has been shown that the placement of the LV lead in the posterolateral branch shows better improvement in cardiac function than the placement of the LV lead in the anterior great cardiac vein or the medial vein;16,17 others have shown no difference in long-term benefit of LV placing site.¹⁷ The issue of whether LV lead placement in the most delayed segment leads to maximum improvement from CRT remains unsettled. While studies have shown that concordance of LV position with the most delayed LV segment results in maximum improvement in cardiac output,^14,18 no studies have placed LV leads intraprocedurally, guided by echocardiography. Other studies have shown lack of benefit of CRT if the anterior wall and anterior interventricular septum are the most delayed segments.¹⁹ Appropriate placement of LV lead in the coronary sinus branch may be hampered by lack of a branch vein in the appropriate territory, lack of suitable anatomy for lead placement including tortuosity of the branch, acute angulation at origin, narrow caliber, or diaphragmatic stimulation when the lead is placed in the appropriate vein. In addition, in at least 5% of patients there is dislodgement of the LV lead after initial successful placement. In an additional number, there is an increase in the lead thresholds or loss of capture that may lead to loss of biventricular pacing. In general, the larger the diameter of the target coronary sinus vein at implantation, the easier it is to be successfully cannulated, but the easier it is for the lead to dislodge; the more difficult it is to place the LV lead during implantation due to angulation, etc., the more stable the lead position after implantation. Assessment of coronary venous system by multi-slice computed tomography (CT) prior to CRT may improve selection of patients for percutaneous versus epicardial CRT.²⁰ Other methods being tested include magnetic wire navigation using stereotaxis and endoscopic and pericardial approaches.^21,22