Effects of Atrioventricular Optimization on Left Ventricular Reverse Remodeling With Cardiac Resynchronization Therapy: Results of the SMART-CRT Trial.

BACKGROUND: The role of atrioventricular optimization (AVO) to improve cardiac resynchronization therapy outcomes remains controversial. Previous post hoc analyses of a multicenter trial showed that measures of electrical dyssynchrony (right ventricular-left ventricular [LV] or LV electrical delay durations) are associated with patients who benefit from AVO. METHODS: This was a global, multicenter, prospective, randomized trial of de novo cardiac resynchronization therapy implant patients with an right ventricular-LV duration ≥70 ms to determine whether AVO results in greater reverse remodeling. Patients were randomized 1:1 for either an AVO algorithm (SmartDelay) that determines atrioventricular delay and pacing chamber, biventricular or LV only, or a fixed atrioventricular delay of 120 ms with biventricular pacing. Paired echocardiograms performed at baseline and 6 months were evaluated. The primary end point was echocardiographic cardiac resynchronization therapy response, defined dichotomously as a >15% reduction in LV end-systolic volume. RESULTS: A total of 310 patients (n=120 women) were randomized and had completed 6 months of follow-up. The echocardiographic cardiac resynchronization therapy response rate did not statistically differ between the groups (SmartDelay, 74.8%; fixed, 67.7%; P=0.17). Analyses of prespecified secondary end points demonstrated significant improvements in the absolute (median: SmartDelay, -41.0 mL; fixed, -33.0 mL; P=0.01) and relative change in LV end-systolic volume (SmartDelay, -38.3%; fixed, -27.8%; P=0.03) for patients with SmartDelay optimization. Similar results were observed for the relative improvement in LV ejection fraction (SmartDelay, 46.7%; fixed, 32.1%; P=0.050); absolute improvement in LV ejection fraction trended to be higher with SmartDelay (P=0.06). CONCLUSIONS: Analysis of reverse remodeling parameters demonstrated that AVO via SmartDelay, relative to the nonoptimized fixed atrioventricular delay comparator group, improved absolute and relative changes in LV function in patients with longer right ventricular-LV duration. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03089281.

The rationale and design of the SMART CRT trial.

AIMS: The SMART CRT study will assess the efficacy of an atrioventricular optimization algorithm to improve reverse remodeling among patients undergoing cardiac resynchronization therapy (CRT) in the presence of interventricular electrical delay. METHODS AND RESULTS: The SMART CRT study is a global, multicenter, prospective, randomized study of patients undergoing CRT implantation. The primary endpoint of this trial is response rate to CRT, defined as decrease in left ventricular end-systolic volume (LVESV) ≥15% at 6 months compared to preimplant baseline. Additional prespecified analyses are: (1) clinical composite endpoint combining all-cause mortality, heart failure events, New York Heart Association class, and Quality of Life (using a patient global assessment instrument); (2) the individual components of the clinical composite endpoint; (3) 6-minute walk distance; (4) Kansas City Cardiomyopathy Questionnaire; (5) LVESV as a continuous variable; and (6) absolute left-ventricular ejection fraction. Subjects with intraventricular delay ≥ 70 ms measured between the right ventricular and left ventricular pacing leads will be randomized in a 1:1 ratio to have either an AV Delay and pacing chamber determined by SmartDelay™ or a Fixed AV Delay of 120 ms with biventricular pacing. Enrollment of an estimated 726 of subjects from up to 100 centers worldwide is planned to achieve 436 randomized subjects and 370 complete data sets required to power the primary endpoint. CONCLUSIONS: This trial will provide important data regarding the importance of AV Delay programming in patients with prolonged interventricular delay at the pacing sites.

Guidewire Method for Measuring Local Left Ventricular Electrical Activation Time During Cardiac Resynchronization Implantation.

The timing of local activation at left ventricular (LV) pacing leads is measured from the onset of the QRS complex to the peak of the LV electrogram (QLV). Pacing from the sites of late activation is associated with higher response rates to cardiac resynchronization therapy (CRT). Prior studies have measured QLV from permanent pacing leads, or have used electroanatomic mapping systems. The current study compares QLV measurements made with a guidewire to those collected from permanent LV pacing leads positioned at the same venous site without the use of electroanatomic mapping systems. In this study, 20 patients undergoing CRT implantation (14 males, mean QRS: 164.0 ms) had QLV measurements taken using a guidewire. QLV and LV electrogram duration measurements were made at LV pacing sites, and were repeated after positioning the permanent LV pacing lead at the same site. There was no difference in QLV measurements obtained using a guidewire and those obtained using the permanent pacing lead placed at the same site (p = 0.569). QLV measurements obtained with a guidewire and the permanent LV pacing lead at the same site, respectively, were strongly correlated (r = 0.965; p < 0.001). The median absolute difference in electrogram duration was 7.0 ms (p = 0.55). The average time required to make QLV measurements using the guidewire was 11.7 minutes [standard deviation (SD): 6.8]. The average total fluoroscopy time for the entire CRT implant procedure was 10.9 minutes (SD: 5.1). In light of these results, it can be suggested that a guidewire can be used to prospectively measure LV prior to selection or placement of a permanent pacing lead without the use of an electroanatomic mapping system.