Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy. The TARGET Study: A Randomized, Controlled Trial
Is targeted coronary sinus (CS) lead placement superior to usual care in patients with heart failure (HF) receiving cardiac resynchronization therapy (CRT)?
The TARGET Study was a two-center, randomized (1:1 ratio), controlled trial of CS lead placement guided by speckle tracking echocardiography in patients undergoing CRT implant according to present criteria. Speckled tracking 2D radial strain analysis was performed in the intervention group using the mid left ventricular (LV) segment for analysis. CS lead placement was targeted to the myocardial region with the latest timing to peak contraction devoid of scar characteristics (deformation amplitude >10%). CRT response was defined as a ≥15% reduction in LV end-systolic volume at 6 months following device implant. The primary endpoint was response to CRT.
Patient age (median 72 years), sex (77-80% male), coronary artery disease burden (56% had ischemic cardiomyopathy), and New York Heart Association (NYHA) class (93-95% class III, remainder class IV) were similar between the groups. Baseline LV ejection fraction (EF) was 23%. Data in patients with failed CS lead placements (n = 7) or those who were lost to follow-up (n = 11) or died prior to randomization (n = 2) were excluded. Thus, 103 patients in the intervention group and 104 patients in the control group were analyzed for outcomes. Procedure complications and procedural lengths were similar between the groups, but screening times were longer in the intervention group (25 ± 14 vs. 19 ± 13 minutes, p = 0.033). Following 6 months of therapy, 70% of patients in the intervention group compared with 55% of controls were responders (p = 0.031). EF improved by 8 ± 7% versus 5 ± 8% in the intervention vs. target group, respectively (p = 0.001). Similarly, NYHA functional class (-1.1 ± 0.7 vs. -0.08 ± 0.7, p = 0.002) and 6-minute walk test (6MWT) distances (+61 ± 76 vs. +38 ± 76 m, p = 0.011) improved with targeted CRT. Over 2 years, there were 22 deaths (10%) and 18 (8%) HF admissions. Kaplan-Meier survival was similar between the two groups (log rank p = 0.30), but the combined endpoint of death/HF hospitalization was less in patients with targeted LV pacing. Further, patients without scar at the LV pacing site had better Kaplan-Meier survival (p = 0.0034) than those with scar.
The authors concluded that targeted CS lead placement leads to improved outcomes in patients undergoing CRT.
This paper is accompanied by a nice editorial by Dr. Jalal Ghali in JACC. Overall, it appears that targeting CS lead placement to myocardial regions that are devoid of scar with the most delayed electrical activation leads to better CRT response. In this small study, it is hard to draw conclusions about survival. The difference in 6MWT distances (improved by ~23 m in the intervention group) were statistically significant, but of arguable clinical significance. However, the marked drop in rehospitalization is intriguing and, in a condition with an ~30% readmission rate, rehospitalization gains are clinically important. Unfortunately, while speckle tracking may provide a ‘road map’ for CS lead placement, obstacles such as CS anatomy may preclude lead placement in the ‘target’ area. In the intervention group, LV lead placement was relegated to areas of scar in 8%, and approximately one-third of intervention patients could not achieve ‘concordant’ pacing configurations. However, when traveling, I suspect electrophysiologists would rather leave with a map in hand than nothing at all…
Keywords: Myocardial Ischemia, Coronary Artery Disease, Coronary Sinus, Lost to Follow-Up, New York, Cardiac Resynchronization Therapy, Cicatrix, Cardiomyopathies, Heart Failure, Hospitalization, Heart Ventricles, Echocardiography
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