Optimal pacing sites in cardiac resynchronization by left ventricular activation front analysis

Highlights

• The high non-response rate remains the Achilles' heel of CRT.

• Maximum Activation Front is a potential marker for patient selection.

• Multisite pacing may be worse than single site and is only favourable if optimized.

• Triple site LV pacing is an overkill.

• Computational models are getting closer to clinical use.

Abstract

Cardiac resynchronization therapy (CRT) can substantially improve dyssynchronous heart failure and reduce mortality. However, about one-third of patients who are implanted, derive no measurable benefit from CRT. Non-response may partly be due to suboptimal activation of the left ventricle (LV) caused by electrophysiological heterogeneities. The goal of this study is to investigate the performance of a newly developed method used to analyze electrical wavefront propagation in a heart model including myocardial scar and compare this to clinical benchmark studies. We used computational models to measure the maximum activation front (MAF) in the LV during different pacing scenarios. Different heart geometries and scars were created based on cardiac MR images of three patients. The right ventricle (RV) was paced from the apex and the LV was paced from 12 different sites, single site, dual-site and triple site. Our results showed that for single LV site pacing, the pacing site with the largest MAF corresponded with the latest activated regions of the LV demonstrated during RV pacing, which also agrees with previous markers used for predicting optimal single-site pacing location. We then demonstrated the utility of MAF in predicting optimal electrode placements in more complex scenarios including scar and multi-site LV pacing. This study demonstrates the potential value of computational simulations in understanding and planning CRT.

Introduction

Heart failure (HF) is a major health and socio-economic problem affecting more than 26 million people globally. Prevalence is increasing as the population is getting older[1]. About one-third of HF patients have disorders of the cardiac conduction system causing dyssynchronous ventricular contraction and relaxation patterns, characterized by prolonged QRS duration seen on 12-lead ECG[2]. Cardiac Resynchronization Therapy (CRT) may improve pumping mechanism and HF symptoms for such patients[3,4], however about 30% of patients selected according to international guidelines do not respond to CRT[4,5]. In a subset of patients, non-response can be explained by suboptimal activation of the left ventricle (LV)[6]. Strategies for selection of pacing sites using preoperative or acute clinical parameters have been disappointing [7]and multicentre trials have not provided specific or sensitive response-related acute factors predicting results from CRT[8], nor provided evidence of an optimal pacing configuration [8,9]. This leaves us with the paradox that to benefit the majority of patients with an indication for CRT, a minority will experience adverse outcomes[10].

Advances in computational modeling of heart-function have made it possible to evaluate different aspects of CRT in a controlled, analytical setting[11], such as evaluating optimal single-site pacing (SSP) from the LV related to scar location[12,13] and scar size[14]. Other studies focused on creating patient-specific models to aid CRT implementation[15]. The lack of a standard method for the prediction of CRT outcomes has led to a variety of computational studies that have used various intra-procedural, electrophysiological measurements to alleviate this problem. Pressure gradients dP/dt_max[15], electromechanical activation sequences[16], ATP consumption heterogeneity[17], and LV endocardium activation times[18] have been used without consistent success.

In this study, we investigated the electrical activation propagation throughout the ventricles and introduce the term maximum activation front (MAF) as a potential outcome measurement in a detailed electrophysiological model of infarcted left ventricles. The main objective of the study was to evaluate this novel parameter and to compare it with standard observations used for CRT therapy. Current clinical evidence implies that the optimal LV pacing site is in the latest, spontaneously activated area[2,9]. We hypothesized that pacing in these areas would produce the highest MAF values. Our secondary objective was to test how building a model for theoretical optimal resynchronization by pacing from multiple nodes could become a benchmark for testing in clinical multisite CRT-pacing.

In section 2, the computational model framework and the study design are described, followed by results in section 3. Finally, the results are discussed, and conclusions are drawn in section 4.