Clinical Relevance Of Systematic CRT Device Optimization

Abstract

Cardiac Resynchronization Therapy (CRT) is known as a highly effective therapy in advanced heart failure patients with cardiac dyssynchrony. However, still one third of patients do not respond (or sub-optimally respond) to CRT. Among the many contributors for the high rate of non-responders, the lack of procedures dedicated to CRT device settings optimization (parameters to regulate AV synchrony and VV synchrony) is known as one of the most frequent. The most recent HF/CRT Guidelines do not recommend to carry-out optimization procedures in every CRT patient; they simply state those procedures "could be useful in selected patients", even though their role in improving response has not been proven. Echocardiography techniques still remain the gold-standard reference method to the purpose of CRT settings optimization. However, due to its severe limitations in the routine of CRT patients management (time and resource consuming, scarce reproducibility, inter and intra-operator dependency), echocardiography optimization is widely under-utilized in the real-world of CRT follow-up visits. As a consequence, device-based techniques have been developed to by-pass the need for repeated echo examinations to optimize CRT settings. In this report the available device-based optimization techniques onboard on CRT devices are shortly reviewed, with a specific focus on clinical outcomes observed in trials comparing these methods vs. clinical practice or echo-guided optimization methods. Particular emphasis is dedicated to hemodynamic methods and automaticity of optimization algorithms (making real the concept of "ambulatory CRT optimization"). In fact a hemodynamic-based approach combined with a concept of frequent re-optimization has been associated - although retrospectively - with a better clinical outcome on the long-term follow-up of CRT patients. Large randomized trials are ongoing to prospectively clarify the impact of automatic optimization procedures.

Figure 1.. Top panel: QuickOpt IEGM method to determine the optimal sensed AVD value Bottom panel: SmartDelay IEGM method to determine the optimal paced and sensed AVD values; LRL = Lower Rate Limit (basic pacing rate)

Figure 2.. Response Rate at 6-month follow-up (Packer’s clinical combined endpoint) observed in the Adaptive-CRT trial. Dark-grey hystograms: prospective randomized comparison (non-inferiority). Light-grey hystogram: average response rate from historical CRT cohorts.

Figure 3.. Left panel: effects of AV-synchrony on the SonR signal, given by the overlapping effects of contractility (LVdP/dt max) and mitral leaflets movements on myocardial vibrations; this model allows to determine the optimal AVD by simply modulating the AV timings and interpolating the corresponding SonR curve. The optimal AVD corresponds to the inflection point of the SonR-sigmoid (green-curve). Right panel: effects of VV-synchrony on the SonR signal. For each VV delay, the SonR algorithm carries-out an AVD scanning, to determine which ventricular resynchronization configuration (VVD) provides with the maximum area under the curve (corresponding to the “best average contractility” over a spectrum of real-life variable filling conditions).

Figure 4.. Endpoints at 12-month follow-up visit observed in the CLEAR pilot study and related authors’ conclusions. The rate of clinical responders (Packer’s combined criterion) significantly differs among the two groups. Other hystograms represent secondary endpoints (single components of Packer’s endpoint).

Figure 5.. Design of the prospective randomized double-blinded RESPOND-CRT trial. Patients are 2:1 randomized (respectively) to: left arm) activation of the SonR automatic CRT settings optimization function; right arm) single echo-optimization of CRT settings soon after implant (before hospital discharge) without activating the SonR automatic function. Clinical judgment during 2-year follow-up is provided by an independent group of blinded investigators.

Figure 6.. Rate of clinical response at 12-month follow-up (Packer’s combined criterion) among group of CRT patients in the CLEAR and FREEDOM trials. The comparison is purely qualitative (different populations, different study design, etc.); however, the overall impression is that a systematic optimization (ambulatory repeated procedures over time) provide patients with a better clinical outcome (to be prospectively confirmed by ongoing trials). References: CLEAR ITT (Intention-To-Treat), ref.[20]; FREEDOM, ref.[11]; CLEAR post-hoc, ref.[22].