Non-invasive three-dimensional electrical activation mapping to predict cardiac resynchronization therapy response: site of latest left ventricular activation relative to pacing site

Abstract

Aims: Pacing remote from the latest electrically activated site (LEAS) in the left ventricle (LV) may diminish response to cardiac resynchronization therapy (CRT). We tested whether proximity of LV pacing site (LVPS) to LEAS, determined by non-invasive three-dimensional electrical activation mapping [electrocardiographic Imaging (ECGI)], increased likelihood of CRT response.

Methods and results: Consecutive CRT patients underwent ECGI and chest/heart computed tomography 6-24 months of post-implant. Latest electrically activated site and the distance to LVPS (dp) were assessed. Left ventricular end-systolic volume (LVESV) reduction of ≥15% at clinical follow-up defined response. Logistic regression probabilistically modelled non-response; variables included demographics, heart failure classification, left bundle branch block (LBBB), ischaemic heart disease (IHD), atrial fibrillation, QRS duration, baseline ejection fraction (EF) and LVESV, comorbidities, use of CRT optimization algorithm, angiotensin-converting enzyme inhibitor(ACE)/angiotensin-receptor blocker (ARB), beta-blocker, diuretics, and dp. Of 111 studied patients [64 ± 11 years, EF 28 ± 6%, implant duration 12 ± 5 months (mean ± SD), 98% had LBBB, 38% IHD], 67% responded at 10 ± 3 months post CRT-implant. Latest electrically activated sites were outside the mid-to-basal lateral segments in 35% of the patients. dp was 42 ± 23 mm [31 ± 14 mm for responders vs. 63 ± 24 mm non-responders (P < 0.001)]. Longer dp and the lack of use of CRT optimization algorithm were the only independent predictors of non-response [area under the curve (AUC) 0.906]. dp of 47 mm delineated responders and non-responders (AUC 0.931).

Conclusion: The distance between LV pacing site and latest electrical activation is a strong independent predictor for CRT response. Non-invasive electrical evaluation to characterize intrinsic activation and guide LV lead deployment may improve CRT efficacy.

Keywords: Cardiac resynchronization therapy; Dilated cardiomyopathy; ECGI; Electrocardiographic imaging; Heart failure; Ischaemic cardiomyopathy; Non-invasive 3D electrical activation mapping.

Graphical Abstract

Figure 1

(A) Body surface potential acquisition; 224 electrodes were applied to the patient’s torso (1), and unipolar body surface potentials were acquired during native rhythm (2). On CT, a torso scan (3) and a contrast-enhanced heart scan during breath hold (4) were performed while the electrodes were still attached to the torso. (B) Processing the body surface recordings; A mesh model of the torso was generated, and electrode positions were identified (5). The ventricles were segmented on the cardiac scan and a mesh model was generated (6). The LVPS was identified on the cardiac scan and its location marked on the ventricular mesh model (7). The inverse calculation yielded a time series of isopotential maps (8) on which the LEAS was identified and the geodesic distance d_p to the LVPS measured (9). CT, computed tomography; LV, left ventricle; LVPS, left ventricular pacing site; LEAS, latest electrically activated LV site.

Figure 2

Eighteen-segment polar plot model showing the positions and distribution of the LVPS (A) and LEAS (B). Responders are shown in blue and non-responders in red. (C) Examples of LVPS (lighter colour) and the corresponding LEAS (darker colour) positions for three responders: For patient n° 77, an anterior LEAS was matched well with an anterior LVPS, similar for the other patients with both LEAS and LVPS in the lateral and posterolateral segment, respectively. (D) Examples of LVPS (lighter colour) and the corresponding LEAS (darker colour) positions for four non-responders: For patient n° 21, the LVPS was placed in a lateral position, whereas the LEAS lay anteriorly. For patient n° 98, it was the other way round with LEAS in the lateral segment whereas the LVPS was placed in an anterolateral position. Similarly, for patients n° 12 and 73, where LVPS and LEAS positions did not match. LV, left ventricle; LVPS, left ventricular pacing site; LEAS, latest electrically activated LV site.

Figure 3

Logistic regression model building. Forest plot with odds ratio (OR) and 95% confidence interval (CI) for the result of the univariate analysis (A), the subsequent multivariate analysis (B), and the ROC curve of the final logistic regression model including only the two variables distance d_p and the use of CRT optimization algorithm with an AUC of 0.906 (C).

Figure 4

A plot for all patients (n = 111) where the distance d_p is shown on the x-axis and LVESV reduction on the y-axis (left panel). The dashed horizontal line divides responders (LVESV reduction ≥ 15%) and non-responders (LVESV reduction < 15%). The dashed vertical line corresponds to d_p = 47 mm, the cut-off value that provides the best balance between sensitivity and specificity for responders and non-responders (blue dots - true responders, black dots - true non-responders, red dots - false responders and green dots - false non-responders). The corresponding ROC curve for the optimal cut-off point analysis with d_p = 47 mm (right panel). AUC, area under the curve; LVESV, left ventricular end-systolic volume; ROC, receiver operating characteristics.