Advanced image-supported lead placement in cardiac resynchronisation therapy: protocol for the multicentre, randomised controlled ADVISE trial and early economic evaluation

Abstract

Introduction: Achieving optimal placement of the left ventricular (LV) lead in cardiac resynchronisation therapy (CRT) is a prerequisite in order to achieve maximum clinical benefit, and is likely to help avoid non-response. Pacing outside scar tissue and targeting late activated segments may improve outcome. The present study will be the first randomised controlled trial to compare the efficacy of real-time image-guided LV lead delivery to conventional CRT implantation. In addition, to estimate the cost-effectiveness of targeted lead implantation, an early decision analytic model was developed, and described here.

Methods and analysis: A multicentre, interventional, randomised, controlled trial will be conducted in a total of 130 patients with a class I or IIa indication for CRT implantation. Patients will be stratified to ischaemic heart failure aetiology and 1:1 randomised to either empirical lead placement or live image-guided lead placement. Ultimate lead location and echocardiographic assessment will be performed by core laboratories, blinded to treatment allocation and patient information. Late gadolinium enhancement cardiac magnetic resonance imaging (CMR) and CINE-CMR with feature-tracking postprocessing software will be used to semi-automatically determine myocardial scar and late mechanical activation. The subsequent treatment file with optimal LV-lead positions will be fused with the fluoroscopy, resulting in live target-visualisation during the procedure. The primary endpoint is the difference in percentage of successfully targeted LV-lead location. Secondary endpoints are relative percentage reduction in indexed LV end-systolic volume, a hierarchical clinical endpoint, and quality of life. The early analytic model was developed using a Markov-model, consisting of seven mutually exclusive health states.

Ethics and dissemination: The protocol was approved by the Medical Research Ethics Committee Utrecht (NL73416.041.20). All participants are required to provide written informed consent. Results will be submitted to peer-reviewed journals.

Trial registration number: NCT05053568; Trial NL8666.

Keywords: MRI; cardiovascular imaging; heart failure; pacing & electrophysiology.

Figure 1

Flow-chart presenting the course of the study. Legend: AV, atrioventricular; LVAD, left ventricle assist device; MRI, magnetic resonance imaging; NYHA, New York Heart Association; VV, interventricular.

Figure 2

SPIRIT time schedule of enrolment, interventions and assessments for the ADVISE trial. ^aImplantation time, radiation exposure and electrode configurations. ^bFor example, indices of mechanical resynchronisation, such as apical rocking. Legend: ADVISE, advanced image supported lead placement in CRT; HF, heart failure; LVESVi, left ventricular end-systolic volume indexed to body surface area; SPIRIT, Standard Protocol Items: Recommendations for Interventional Trials.

Figure 3

Workflow for advanced image-guided LV-lead placement. Adapted from Wouters et al. Legend: CMR, cardiac MRI; LV, left ventricular.

Figure 4

Seven ‘health states’ (squares) were defined. Patients either remain in their state during follow-up (inward arrows), or relocate towards the next sequential health state (uninterrupted arrows). Each transition is assigned its own probability of occurrence. When death occurs, other health states may be skipped (dashed arrows). Note that the assumption was made that post-CRT patients with ≤2 decompensations will not receive LVAD or transplantation. Legend: CRT, cardiac resynchronisation therapy; LVAD, left ventricle assist device.

Figure 5

(A) Cost-effectiveness plane for image-guided lead placement. The graph shows the iterations (blue dots) in comparison to the cost-effectiveness thresholds for €30 000/QALY and €80 000/QALY (red and blue lines). (B) Potential cost savings with image-guided lead placement, based on the proportional difference in responders. Legend: ICER, incremental cost-effectiveness ratio (Δ€/ΔQALY); QALY, quality adjusted life year.