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

Chronic Heart Failure Clinical Trial

— CRT-DRIVE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05327062
• Other study ID #: CRT-DRIVE_01
• Status: Recruiting
• Phase: N/A
• Start date: March 6, 2023
• Est. completion date: September 2024

Study information

• Verified date: February 2024
• Source: XSpline S.p.A.
• Contact: Claudia M Amatruda, PhD
• Phone: +390471200372
• Email: amatruda[@]xspline.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: September 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bundle-Branch Block
• Cardiac Resynchronization Therapy
• Chronic Heart Failure
• Left Bundle-Branch Block

Intervention

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.

Locations

Country	Name	City	State
Austria	Ordensklinikum Linz Elisabethinen Hospital	Linz
Hungary	Semmelweis University	Budapest
Italy	General Hospital of Bolzano	Bolzano
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	University Tor Vergata	Roma
Italy	Ospedale S. Maria del Carmine di Rovereto	Rovereto
Netherlands	Maastricht University Medical Center	Maastricht
Spain	Univeristat de Barcelona	Barcelona
Switzerland	Istituto Cardiocentro Ticino	Lugano
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Rush University Medical center	Chicago	Illinois
United States	The University of Chicago Medicine	Chicago	Illinois
United States	Duke University Hospital	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
XSpline S.p.A.

Countries where clinical trial is conducted

United States,  Austria,  Hungary,  Italy,  Netherlands,  Spain,  Switzerland, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl (2011) [Internet] 2013;3(1):163. Available from: https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf

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. — View Citation

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. — View Citation

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

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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