Cardiac Resynchronization Therapy Delivery Guided Non-Invasive Electrical and Venous Anatomy Assessment (CRT-DRIVE)

CRT-DRIVE: Cardiac Resynchronization Therapy Delivery Guided Non-Invasive Electrical and Venous Anatomy Assessment

The objective of this prospective, multicenter controlled study is to assess the feasibility of a patient-tailored implantation by creating a cloud-based pre-procedural multimodality CRT-roadmap by integration of 3D images from 3D activation sequence from ECG, and coronary venous anatomy from cardiac computed tomography. This CRT-roadmap will be used to guide LV lead placement to a coronary vein in an electrically late-activated region.

Study Hypothesis: At least 75% of patients undergoing a CRT implantation guided by non-invasive electrical and venous anatomy assessment (XSPLINE technology) will show a reduction of left ventricular end-systolic volume of 15% or more at 6-month evaluation.

Study Overview

• Status: Recruiting
• Conditions: Left Bundle-Branch Block; Chronic Heart Failure; Cardiac Resynchronization Therapy
• Intervention / Treatment: Device: CRT implantation guided by XSpline, a non-invasive electrical and venous anatomy assessment

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Claudia M Amatruda, PhD; Phone Number: +390471200372; Email: amatruda@xspline.com

Study Locations

• Austria
  • Linz, Austria
    • Recruiting
    • Ordensklinikum Linz Elisabethinen Hospital
    • Contact: Helmut Puererfellner; Email: helmut.puererfellner@ordensklinikum.at
    • Contact: Georgios Kollias, MSc
• Hungary
  • Budapest, Hungary
    • Not yet recruiting
    • Semmelweis University
    • Contact: Bela Merkely; Email: merkely.bela@gmail.com
    • Contact: Bela Merkely, PhD DSc FESC
• Italy
  • Bolzano, Italy
    • Not yet recruiting
    • General Hospital of Bolzano
    • Contact: Rainer Oberhollenzer; Email: rainer.oberhollenzer@sabes.it
    • Contact: Rainer Oberhollenzer, MD
  • Pavia, Italy
    • Not yet recruiting
    • Fondazione IRCCS Policlinico San Matteo
    • Contact: Roberto Rordorf, MD; Email: R.Rordorf@smatteo.pv.it
  • Roma, Italy
    • Not yet recruiting
    • University Tor Vergata
    • Contact: Claudia Tamburro, MD; Email: claudia.tamburro96@gmail.com
  • Rovereto, Italy
    • Not yet recruiting
    • Ospedale S. Maria del Carmine di Rovereto
    • Contact: Maurizio del Greco, MD; Email: maurizio.delgreco@apss.tn.it
• Netherlands
  • Maastricht, Netherlands
    • Not yet recruiting
    • Maastricht University Medical Center
    • Contact: Kevin Vernooy; Email: kevin.vernooy@mumc.nl
    • Contact: Kevin Vernooy, MD
• Spain
  • Barcelona, Spain
    • Recruiting
    • Univeristat de Barcelona
    • Contact: Lluis Mont; Email: lmont@clinic.cat
    • Contact: Mont, MD
• Switzerland
  • Lugano, Switzerland
    • Recruiting
    • Istituto Cardiocentro Ticino
    • Contact: Angelo Auricchio; Email: angelo.auricchio@eoc.ch
    • Contact: Tardu Özkartal, MD
• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Not yet recruiting
      • The University of Chicago Medicine
      • Contact: Gaurav Upadhyay; Email: gupadhyay@medicine.bsd.uchicago.edu
      • Contact: Gaurav Upadhyay, MD
    • Chicago, Illinois, United States, 60637
      • Not yet recruiting
      • Rush University Medical Center
      • Contact: Parikshit S Sharma; Email: parikshit_S_Sharma@rush.edu
      • Contact: Parikshit S Sharma, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Jag Singh; Email: JSINGH@mgh.harvard.edu
      • Contact: William J Hucker, MD, PhD
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Hospital
      • Contact: Daniel Friedman, MD
      • Contact: Daniel Friedman; Email: daniel.friedman@duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Eligible subjects shall meet all following criteria:

• Appropriately signed and dated informed consent.
• Age ≥18 years at time of consent.
• CRT indication according to the 2021 ESC guidelines on cardiac pacing and CRT (class I and IIA indication in patients with LBBB QRS morphology) or to 2017 AHA/ACC/HFSA guidelines (COR I).
• Sinus rhythm
• QRS duration ≥130 ms
• Left bundle branch block
• Left ventricular ejection fraction ≤35%
• Symptomatic heart failure NYHA class ≥ II
• Documented stable medical treatment for at least 6 months
• No cardiovascular intervention during the last 6 month

Exclusion Criteria are:

• History of persistent or permanent atrial fibrillation
• Previous pacemaker or ICD implantation
• Indication to pacing due to bradycardia
• Patients considered for His bundle pacing or cardiac conduction pacing
• Patients with unstable angina
• Subject experienced a recent myocardial infarction, within 40 days prior to enrollment
• Subject underwent coronary artery bypass graft or valve surgery, within 90 days prior to enrollment
• Subject is post heart transplantation, or is actively listed on the transplantation list, or has reasonable probability (per investigator's discretion) of undergoing transplantation in the next year
• Subject is implanted with a left ventricular assist device
• Subject is on continuous or uninterrupted infusion (inotropic) therapy for heart failure
• Subject has severe aortic stenosis (with a valve area of <1.0 cm2 or significant valve disease expected to be operated within study period)
• Subject has congenital heart disease
• Subject has a mechanical right-sided heart valve
• Subject has a life expectancy of less than one year in the opinion of the investigator
• Pregnant or breastfeeding women, or women of child bearing potential and who are not on a reliable form of birth control
• Subject is enrolled in one or more concurrent studies that would confound the results of this study
• Patients who have contraindications to CT scanning.
• Patients with chronic kidney diseases and estimated glomerular filtration rate (eGMR) calculated based on CKD-EPI 2009 < 40 ml/min/1.73m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CRT implantation guided by XSpline; The sample size estimation was based on two recent studies including CRT patients with similar clinical and demographic characteristics as in this study: the SMART-MSP and the SMART CRT. The SMART-MSP is a prospective, observational study that enrolled 584 CRT recipients at 52 US sites. In a typical modern CRT population, 75% of patients had a reduction of the end-systolic volume ≥ 15% at 6-month follow-up. The SMART-CRT study enrolled 699 CRT patients randomized to a treatment arm and a control group. At 6-months follow-up, a reduction of LVESV ≥15% was achieved for 67.7% of the patients in the control group and for 74.8% of those in the treatment arm. Therefore, it is assumed that in a modern CRT population at least 70% of the patients will have a reduction of the LVESV ≥15% of the baseline value at 6-months after CRT implantation. To demonstrate that this proportion of patients can be equally achieved with the approach tested in this study at least 150 patients need to be included.

Device: CRT implantation guided by XSpline, a non-invasive electrical and venous anatomy assessment; The following information and data will be obtained from the routine clinical work up of the patients: Patient demographics, cardiovascular medical history, and clinical examination; 12-lead ECG; Standard echocardiography; Computed tomography angiography for visualization of atria, ventricle, and coronary sinus. Imaging data will be transferred to the cloud-based web-platform using a dedicated software provided by study sponsor. Data processing includes evaluating the quality of the data and calculation of various anatomical and electrical parameters, and identification of the target zone as a point in the target vein closest to the latest activation zone. LV-lead location is based on the information provided by the dedicated software followed by visual X-ray based verification of anatomically suitable/most desirable position. The patient will undergo CRT device implantation according to local protocols.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of left ventricular end-systolic volume of at least 15% in 75% of CRT treated patients	Increase in efficacy of CRT using XSpline technology assessed by reduction of left ventricular end-systolic volume of at least 15% at 6-month follow-up in 75% of CRT treated patients, based on routine echo-cardiographic measurements	6 months follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of systematic use of XSpline platform for CRT implantation	Feasibility of systematic use of automatic cloud-based, AI-based XSpline technology through statistics on software performance (e.g. percentage of core tasks completed higher than defined thresholds)	6 months follow-up
CRT procedural time difference	Evaluate the change in CRT procedural time by comparing with standard approach as found in literature, time in minutes	6 months follow-up
Total X-ray exposure time difference	Evaluate the change in total X-ray exposure time by comparing with standard approach as found in literature, time in minutes	6 months follow-up

Collaborators and Investigators

• Sponsor: XSpline S.p.A.
• Investigators: Principal Investigator: Angelo Auricchio, MD PhD FESC, Istituto Cardiocentro Ticino

Publications and helpful links

General Publications

• Andrassy KM. Comments on 'KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease'. Kidney Int. 2013 Sep;84(3):622-3. doi: 10.1038/ki.2013.243. No abstract available.
• Ramanathan C, Ghanem RN, Jia P, Ryu K, Rudy Y. Noninvasive electrocardiographic imaging for cardiac electrophysiology and arrhythmia. Nat Med. 2004 Apr;10(4):422-8. doi: 10.1038/nm1011. Epub 2004 Mar 14.
• Cluitmans MJ, Peeters RL, Westra RL, Volders PG. Noninvasive reconstruction of cardiac electrical activity: update on current methods, applications and challenges. Neth Heart J. 2015 Jun;23(6):301-11. doi: 10.1007/s12471-015-0690-9.
• Pezzuto S, Prinzen FW, Potse M, Maffessanti F, Regoli F, Caputo ML, Conte G, Krause R, Auricchio A. Reconstruction of three-dimensional biventricular activation based on the 12-lead electrocardiogram via patient-specific modelling. Europace. 2021 Apr 6;23(4):640-647. doi: 10.1093/europace/euaa330.
• Zubarev S, Chmelevsky M, Budanova M, Trukshina M, Lyubimtseva T, Lebedeva V, et al. Non-invasive electrophysiological mapping in assessment of association of cardiac resynchronization effect from position of left ventricular electrode. Europace 2017;19(suppl_3):iii326-iii326. doi: 10.1093/ehjci/eux158.182
• Zubarev S, Chmelevsky M, Budanova M, Ryzhkov AV, Trukshina M, Lebedeva V, et al. Comparison of the late activation zone and the changes in the structure of the left ventricular myocardium in candidates for cardiac resynchronization therapy. Europace 2018;20(suppl_1):i54-i54. doi: 10.1093/europace/euy015.145
• Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt OA, Cleland J, Deharo JC, Delgado V, Elliott PM, Gorenek B, Israel CW, Leclercq C, Linde C, Mont L, Padeletti L, Sutton R, Vardas PE; ESC Committee for Practice Guidelines (CPG); Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S; Document Reviewers; Kirchhof P, Blomstrom-Lundqvist C, Badano LP, Aliyev F, Bansch D, Baumgartner H, Bsata W, Buser P, Charron P, Daubert JC, Dobreanu D, Faerestrand S, Hasdai D, Hoes AW, Le Heuzey JY, Mavrakis H, McDonagh T, Merino JL, Nawar MM, Nielsen JC, Pieske B, Poposka L, Ruschitzka F, Tendera M, Van Gelder IC, Wilson CM. 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: the Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J. 2013 Aug;34(29):2281-329. doi: 10.1093/eurheartj/eht150. Epub 2013 Jun 24. No abstract available.
• Glikson M, Nielsen JC, Kronborg MB, Michowitz Y, Auricchio A, Barbash IM, Barrabes JA, Boriani G, Braunschweig F, Brignole M, Burri H, Coats AJS, Deharo JC, Delgado V, Diller GP, Israel CW, Keren A, Knops RE, Kotecha D, Leclercq C, Merkely B, Starck C, Thylen I, Tolosana JM; ESC Scientific Document Group. 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. Eur Heart J. 2021 Sep 14;42(35):3427-3520. doi: 10.1093/eurheartj/ehab364. No abstract available. Erratum In: Eur Heart J. 2022 May 1;43(17):1651. doi: 10.1093/eurheartj/ehac075.

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: March 22, 2022
• First Submitted That Met QC Criteria: April 13, 2022
• First Posted (Actual): April 14, 2022

Study Record Updates

• Last Update Posted (Actual): October 24, 2024
• Last Update Submitted That Met QC Criteria: October 22, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Coronary Sinus; Non-invasive activation mapping
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Heart Block; Bundle-Branch Block
• Other Study ID Numbers: CRT-DRIVE_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No