ClinicalDevicesInvestigation of a novel algorithm for synchronized left-ventricular pacing and ambulatory optimization of cardiac resynchronization therapy: Results of the adaptive CRT trial
Introduction
Cardiac resynchronization therapy (CRT) is an established therapy for patients with heart failure (HF) symptoms, left ventricular systolic dysfunction, and a wide QRS.1, 2 However, the magnitude of clinical and hemodynamic benefit of CRT varies significantly among its recipients with no clinical improvement in approximately one third.1 Patient-specific characteristics, such as severity and type of electrical conduction abnormalities, dyssynchrony, and scar burden, have been associated with the degree of CRT benefit.3, 4
While CRT is most commonly achieved by using biventricular (BiV) pacing, multiple acute5 and randomized chronic6 studies have demonstrated that left-ventricular (LV) pacing can be at least as efficacious as BiV pacing. In patients with sinus rhythm and normal atrioventricular (AV) conduction, pacing only the left ventricle with appropriate AV intervals can result in even superior LV5, 7 and right-ventricular (RV)8, 9 function compared with standard BiV pacing.
Optimization of the AV and interventricular (VV) intervals during BiV pacing is another option to maximize the positive effects of CRT.10, 11 Optimization is usually accomplished by using echocardiography or other modalities. However, these methods can be resource-intensive, and only a minority of clinicians routinely optimize AV and VV delays.
Based on published research,7, 8, 12, 13 a novel adaptive CRT (aCRT) algorithm14 has been developed to provide RV-synchronized LV pacing when AV conduction is normal, or BiV pacing otherwise. AV conduction is considered normal when the Asense to RVsense interval is ≤200 ms. The algorithm also adjusts AV and VV delays on the basis of periodic automatic evaluation of intrinsic conduction intervals. The algorithm is intended to provide ambulatory CRT optimization and allow more physiologic ventricular activation and greater device longevity in patients with normal AV conduction by reducing unnecessary RV pacing. The aim of the aCRT trial was to determine whether the incorporation of this algorithm into the management of CRT patients is safe and efficacious when compared with BiV pacing with echocardiographic AV and VV optimization.
Section snippets
Study design
Details of the algorithm and the aCRT study design have been published previously.14 Briefly, this was a prospective, multicenter, randomized, double-blind, noninferiority clinical trial comparing CRT with settings dynamically adjusted by an investigational aCRT algorithm (aCRT or treatment arm) with standard BiV pacing with AV and VV settings optimized by using a standardized echocardiographic protocol (Echo or control arm). The study enrolled patients who did not have permanent atrial
Study population
A total of 522 patients were enrolled in 94 sites in the United States, Europe, Central Asia, Australia, Canada, Japan, and Hong Kong between November 2009 and December 2010; 478 patients were randomized (318 to the aCRT arm and 160 to the Echo arm). The flow of study patients up to the 6-month postrandomization is shown in Figure 2. The mean follow-up duration was 9.7 ± 3.0 months (range 0.2–19.4 months). Both groups demonstrated similar and acceptable visit compliance throughout the study,
Discussion
The aCRT trial evaluated a novel pacing algorithm for CRT. The design of the algorithm was based on the hypothesis that CRT benefit can further be increased through (1) avoidance of RV pacing and greater recruitment of intrinsic conduction in patients with normal conduction into the right ventricle and (2) dynamic adjustment of AV and VV delays based on the electrical conduction intervals. The aCRT algorithm resulted in a 44% absolute reduction in the percentage of RV pacing. The trial
Conclusions
The aCRT algorithm was safe and at least as effective as BiV pacing with comprehensive echocardiographic optimization across a variety of primary and secondary end points.
Supplement
A complete list of primary investigators in the Adaptive CRT Clinical Trial is available online.
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The trial was sponsored by Medtronic, Mounds View, Minnesota. Dr Martin serves on a Medtronic advisory board. Dr Lemke has received honoraria and speaker's fees from Medtronic and Saint Jude Medical and speaker's fees from Boston Scientific. Dr Birnie has received honoraria and research grants from Medtronic. Dr Krum has received honoraria from Medtronic. Dr Lee has received research grants from Medtronic. Dr Aonuma has received honoraria, speaker's fees, and research grants from Medtronic. Dr Gasparini has received honoraria and served on advisory boards for Medtronic and Boston Scientific. Dr Starling has received honoraria from Novartis. Dr Milasinovic has received honoraria from Medtronic. Dr Gorcsan has consulted for or has received research grants from Biotronik, Medtronic, St Jude Medical, GE, and Toshiba Medical. T. Rogers is a statistician employed by Medtronic. A. Sambelashvili is a scientist employed by Medtronic.