Electrically guided versus imaging-guided implant of the left ventricular lead in cardiac resynchronization therapy: a study protocol for a double-blinded randomized controlled clinical trial (ElectroCRT)

Charlotte Stephansen, Anders Sommer, Mads Brix Kronborg, Jesper Møller Jensen, Kirsten Bouchelouche, Jens Cosedis Nielsen, Charlotte Stephansen, Anders Sommer, Mads Brix Kronborg, Jesper Møller Jensen, Kirsten Bouchelouche, Jens Cosedis Nielsen

Abstract

Background: Cardiac resynchronization therapy (CRT) is an established treatment in patients with heart failure and prolonged QRS duration where a biventricular pacemaker is implanted to achieve faster activation and more synchronous contraction of the left ventricle (LV). Despite the convincing effect of CRT, 30-40% of patients do not respond. Among the most important correctable causes of non-response to CRT is non-optimal LV lead position.

Methods: We will enroll 122 patients in this patient-blinded and assessor-blinded, randomized, clinical trial aiming to investigate if implanting the LV lead guided by electrical mapping towards the latest LV activation as compared with imaging-guided implantation, causes an excess increase in left ventricular (LV) ejection fraction (LVEF). The patients are randomly assigned to either the intervention group: preceded by cardiac computed tomography of the cardiac venous anatomy, the LV lead is placed according to the latest LV activation in the coronary sinus (CS) branches identified by systematic electrical mapping of the CS at implantation and post-implant optimization of the interventricular pacing delay; or patients are assigned to the control group: placement of the LV lead guided by cardiac imaging. The LV lead is targeted towards the latest mechanical LV activation as identified by echocardiography and outside myocardial scar as identified by myocardial perfusion (MP) imaging. The primary endpoint is change in LVEF at 6-month follow up (6MFU) as compared with baseline measured by two-dimensional echocardiography. Secondary endpoints include relative percentage reduction in LV end-systolic volume, all-cause mortality, hospitalization for heart failure, and a clinical combined endpoint of response to CRT at 6MFU defined as the patient being alive, not hospitalized for heart failure, and experiencing improvement in NYHA functional class or/and > 10% increase in 6-minute walk test.

Discussion: We assume an absolute increase in LVEF of 12% in the intervention group versus 8% in the control group. If an excess increase in LVEF can be achieved by LV lead implantation guided by electrical mapping, this study supports the conduct of larger trials investigating the impact of this strategy for LV-lead implantation on clinical outcomes in patients treated with CRT.

Trial registration: ClinicalTrials.gov, NCT02346097 . Registered on 12 January 2015. Patients were enrolled between 16 February 2015 and 13 December 2017.

Keywords: CRT; Cardiac imaging; Cardiac resynchronization therapy; Electrical mapping; Heart failure; LVEF; Left ventricular ejection fraction; Left ventricular lead placement; QLV.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol has been approved by The Central Denmark Region Committees on Health Research Ethics (case number 1–10–72-230-14) (Additional file 1) and by the Danish Data Protection Agency (case number 1–16–02-622-14). All patients give informed written consent prior to enrolment in the study.

Consent for publication

Not applicable as images were anonymized.

Competing interests

CS has attended a conference supported by St Jude Medical. JCO is supported by a grant from the Novo Nordisk Foundation (NNF16OC0018658). MBK has received a speaker’s fee from Biotronik. The other authors have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Consort diagram of the study course. 6MWT, 6-minute walk test; AV, atrioventricular; CRT, cardiac resynchronization therapy; CT, computed tomography; LV, left ventricular; LVEF, left ventricular ejection fraction; MLHFQ, Minnesota Living with Heart Failure Questionnaire; MP, myocardial perfusion; NYHA, New York Heart Association; QoL, quality of life; VVd, interventricular pacing delay
Fig. 2
Fig. 2
Control group: pre-implant imaging obtained to guide implantation of the left ventricular (LV) lead. a Echocardiographic LV short-axis view of the basal (left) and mid-LV imaging plane (right) each divided into six anatomical segments. Numbers indicate time to peak radial strain in milliseconds (ms). b Baseline cardiac computed tomography (CT) images in three-dimensional 3D reconstruction illustrating cardiac venous anatomy. Posterior (left) and lateral (right) view of LV. c Baseline cardiac CT image in the mid-LV multiplanar reformatted short-axis view illustrating cardiac venous anatomy. d Rubidium positron emission tomography (Rb-PET) myocardial perfusion (MP) imaging, LV 17-segment bulls-eye plot. Numbers indicate percentage of tracer-uptake; < 50% is considered as transmural scar tissue. AIV, anterior interventricular vein; Ant, anterior; Ant-Sept, antero-septal; CS, coronary sinus; Inf, inferior; LAD, left anterior descending artery; Lat, lateral; LMA, left marginal artery (circumflex artery branch); LMV, left marginal vein; MCV, middle cardiac vein; PDA, posterior descending artery (right coronary artery branch); PLA, posterolateral artery; Post, posterior; PV, posterior vein; RCA, right coronary artery; RV, right ventricle; Sept, septal
Fig. 3
Fig. 3
Intervention group: electrical mapping. The local electrical activation delay is measured as time in milliseconds (ms) from QRS onset in the surface 12-lead electrocardiogram (ECG) to the maximum voltage change over time recorded in the local LV electrogram (EGM), reflecting the near-field activation of the myocardium according to the LV lead (QLV interval). The figure shows three examples of QLV measurements with the LV lead in a basal, mid, and apical position, exhibiting the longest QLV interval in the apical position. For simplicity, only the surface leads V2 and V6 and the local LV EGM (Pace 1–2) are shown
Fig. 4
Fig. 4
SPIRIT figure of the ElectroCRT study protocol. ECG, electrocardiogram; NYHA, New York Heart Association; MLHFQ, Minnesota Living with Heart Failure Questionnaire; 6MWT, 6-minute walk test; Rb-PET MP, rubidium positron emission tomography myocardial perfusion imaging; CT, computed tomography; VV, interventricular; AV, atrioventricular; LV, left ventricular; LVEF, left ventricular ejection fraction; LVESV, left ventricular end-systolic volume, CRT, cardiac resynchronization therapy; 6MFU, 6-month follow up; QoL, quality of life; Nt Pro-BNP, N-terminal prohormone of brain natriuretic peptide, LVEDV, left ventricular end-diastolic volume

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