Optimal pacing sites in cardiac resynchronization by left ventricular activation front analysis
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/dtmax[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.
Section snippets
Geometric data
The geometric models used in this study were generated using contrast-enhanced cardiac MRI to reconstruct patient-specific 3D meshes of the ventricles. A detailed description of the model creation can be found in Refs. [19] and is summarized here. Ventricular MRI slices were semi-automatically segmented into four areas, separating LV and RV endo- and epicardium, using Segment™ (Medviso, Sweden). Infarcted regions – appearing white in the contrast-enhanced MRI images – were segmented in each
Single-site pacing (SSP)
To evaluate the propagation delay between the RV site and the different LV sites, we recorded the activation time at the 12 LV sites when pacing from only the RV-site i.e. the time it takes the stimulus from the RV-site to reach the different LV sites. Table 1 shows the different timings for all 3 patients with no scar. Note that the posterior sites have the longest activation delay, while the apical sites have the shortest, due to 1) the RV site is closer to the apical sites; 2) the posterior
Discussion
Determining the optimal LV pacing site remains an important challenge in CRT. Suboptimal LV pacing sites may contribute to high non-response rates. Responders are clinically identified based on improved symptoms and echocardiographic evidence of improved cardiac function. Reverse remodeling occurring following implantation is commonly assessed 3–6 months after CRT. Peri-operative measurements, such as maximum LV pressure gradient (dP/dtmax) or TAT measures, have not shown a consistent
Declaration of competing interest
None Declared.
Acknowledgment
This work was funded by the European Union's H2020: MSCA: ITN program for the “Wireless In-body Environment Communication – WiBEC” project under the grant agreement no. 675353.
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