LBBP + CSP Versus LBBP Alone for Cardiac Resynchronization Therapy (LOTTO-CRT)
Left Bundle Branch Pacing + Coronary Sinus Pacing Versus Left Bundle Branch Pacing Alone for Cardiac Resynchronization Therapy in Patients Eligible for CRT-P A Randomized Crossover Pilot Clinical Trial
The purpose of this pilot clinical trial is to evaluate whether a novel cardiac resynchronization strategy, called LOT-CRT, is more effective than standard physiological pacing alone (LBBAP) in patients with heart failure.
This is a randomized, single-center, crossover pilot study involving 10 patients. All participants will receive a specialized pacemaker (CRT-P) with leads implanted in two specific areas: the Left Bundle Branch Area (LBBAP) and the Coronary Sinus (CS).
Because of the crossover design, each patient will serve as their own control, receiving two different pacing configurations in a random order: Active Phase (LOT-CRT): Simultaneous pacing of the left bundle branch and the coronary sinus. Control Phase (LBBAP alone): Pacing only the left bundle branch area. Each treatment phase will last 6 months, for a total follow-up of 12 months per patient.
By testing both strategies in the same patient, this study will help clinicians identify the most effective way to restore heart synchrony and improve clinical outcomes in patients with advanced heart failure and conduction delays.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
This is a single-center, randomized, crossover pilot clinical trial. Each patient will serve as their own control. Following the successful implantation of a device capable of stimulating the LBBAP and the coronary sinus, participants will be randomly assigned to one of two treatment sequences:
Sequence A: LOT-CRT (LBBAP + CS) for 6 months, followed by LBBAP alone Sequence B: LBBAP alone for 6 months, followed by LOT-CRT Each treatment phase will last 6 months, followed by an end-point evaluation and a crossover. Since the hemodynamic effect of electrical stimulation is immediate, no washout period is required between phases.
This study was designed as an exploratory pilot study; therefore, no formal sample size calculation was performed. The number of patients enrolled is considered adequate to assess the feasibility of the procedure, the safety of the crossover design, and to identify preliminary signals of clinical and electrical efficacy.
Studietype
Registrering (Antatt)
Fase
- Ikke aktuelt
Kontakter og plasseringer
Studiesteder
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Antioquia
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Medellín, Antioquia, Colombia, 050036
- Clinica CardioVID
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Beskrivelse
Inclusion Criteria:
- Age ≥18 years
- Standard CRT-P indications according to ESC 2021 (EF ≤50%, QRS ≥130 ms, sinus rhythm or controlled AF)
- NYHA class II-IV
- Coronary venous anatomy suitable for placement of a coronary sinus electrode.
- Signed informed consent.
- Successful implantation of electrodes in the coronary sinus and in the left bundle branch area (LBBAP)
Exclusion Criteria:
- Concomitant indication for implantation of an implantable cardioverter-defibrillator (ICD) or CRT-D
- Significant uncorrected valvular disease or scheduled or anticipated cardiac surgery during the study period.
- Anatomical or technical contraindication for lead implantation in the coronary sinus or for lead implantation in the coronary sinus (such as sinus stenosis, coronary sinus branches unsuitable for cannulation, inability to advance and/or stabilize the lead, among others)
- Persistent atrial fibrillation with uncontrolled rate
- Comorbidities that may limit life expectancy to <1 year
- Participation in another clinical trial that could confound the evaluation of results within the last 6 months.
- Pregnancy or inadequate contraception
- In the researcher's opinion, the participant would not comply with the activities and visits outlined in the study protocol
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Crossover-oppdrag
- Masking: Dobbelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Aktiv komparator: Sequence A
LOT-CRT (LBBAP + CS) for 6 months, followed by LBBAP alone
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The CS lead will be implanted in a posterolateral or lateral vein using venography and standard IV delivery sheaths. Proper lead placement is confirmed by stable fixation, pacing capture, and absence of diaphragmatic pacing. The configuration for each phase of the study (LOT-CRT or LBBAP alone) will be assigned during randomization.
Andre navn:
The LBBAP lead will be implanted via a transvenous approach using the C315His sheath, targeting the left bundle branch area in the right ventricular septum, ideally between the basal septum and the mid-septal region. Criteria for confirming successful LBBAP capture will include:
Andre navn:
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Aktiv komparator: Sequence B
LBBAP for 6 months only, followed by LOT-CRT
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The CS lead will be implanted in a posterolateral or lateral vein using venography and standard IV delivery sheaths. Proper lead placement is confirmed by stable fixation, pacing capture, and absence of diaphragmatic pacing. The configuration for each phase of the study (LOT-CRT or LBBAP alone) will be assigned during randomization.
Andre navn:
The LBBAP lead will be implanted via a transvenous approach using the C315His sheath, targeting the left bundle branch area in the right ventricular septum, ideally between the basal septum and the mid-septal region. Criteria for confirming successful LBBAP capture will include:
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Compare the effects of the LOT-CRT strategy versus left bundle branch block pacing (LBBAP) alone in each patient, comparing baseline to the end of the study FEVI, quality of life and functional class by NYHA.
Tidsramme: 12 months
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Investigators will evaluate the following parameters in each patient: Left ventricular ejection fraction (LVEF) by echocardiography and electrocardiogram; functional capacity (NYHA class) using the 6-minute walk test and symptoms reported by the patient; quality of life (MLHFQ) using the MLHFQ quality of life scale
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12 months
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Change in end-systolic diameter
Tidsramme: 12 months
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Absolute (mm) and relative (%) change in LVESV between baseline and 6 months.
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12 months
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QRS Duration
Tidsramme: 12 months
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Absolute (ms) and relative (%) changes in the 12-lead ECG.
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12 months
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Change in end-diastolic diameter
Tidsramme: 12 months
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Absolute (mm) and relative (%) change in LVEDV between baseline and 6 months.
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12 months
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NT-proBNP
Tidsramme: 12 months
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Absolute (ng/mL) and relative (%) change in NT-proBNP from baseline to 6 months
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12 months
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Echocardiographic responder
Tidsramme: 12 months
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LVEF ≥10% elevation or LVESV ≥15% decreased
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12 months
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Echocardiographic super-responder
Tidsramme: 12 months
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LVEF ≥50% or LVESV ≥30% decrease
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12 months
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Composite Clinical Outcome
Tidsramme: 12 months
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Cardiovascular Death or Hospitalization for Heart Failure
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12 months
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Procedural parameters
Tidsramme: 12 months
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Thresholds, P- and R-waves, impedance of each electrode.
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12 months
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Procedure Time/Fluoroscopy
Tidsramme: 12 months
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Total procedure time in minutes/ total fluoroscopy time in minutes.
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12 months
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Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Juan F Agudelo, Electrophysiologist, Clinica CardioVID
- Studieleder: Susana Rios, Medical Epidemiologist, Clinica CardioVID
Publikasjoner og nyttige lenker
Generelle publikasjoner
- Su L, Wang S, Wu S, Xu L, Huang Z, Chen X, Zheng R, Jiang L, Ellenbogen KA, Whinnett ZI, Huang W. Long-Term Safety and Feasibility of Left Bundle Branch Pacing in a Large Single-Center Study. Circ Arrhythm Electrophysiol. 2021 Feb;14(2):e009261. doi: 10.1161/CIRCEP.120.009261. Epub 2021 Jan 9.
- Herweg B, Welter-Frost A, Vijayaraman P. The evolution of cardiac resynchronization therapy and an introduction to conduction system pacing: a conceptual review. Europace. 2021 Apr 6;23(4):496-510. doi: 10.1093/europace/euaa264.
- Chung MK, Patton KK, Lau CP, Dal Forno ARJ, Al-Khatib SM, Arora V, Birgersdotter-Green UM, Cha YM, Chung EH, Cronin EM, Curtis AB, Cygankiewicz I, Dandamudi G, Dubin AM, Ensch DP, Glotzer TV, Gold MR, Goldberger ZD, Gopinathannair R, Gorodeski EZ, Gutierrez A, Guzman JC, Huang W, Imrey PB, Indik JH, Karim S, Karpawich PP, Khaykin Y, Kiehl EL, Kron J, Kutyifa V, Link MS, Marine JE, Mullens W, Park SJ, Parkash R, Patete MF, Pathak RK, Perona CA, Rickard J, Schoenfeld MH, Seow SC, Shen WK, Shoda M, Singh JP, Slotwiner DJ, Sridhar ARM, Srivatsa UN, Stecker EC, Tanawuttiwat T, Tang WHW, Tapias CA, Tracy CM, Upadhyay GA, Varma N, Vernooy K, Vijayaraman P, Worsnick SA, Zareba W, Zeitler EP. 2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure. Heart Rhythm. 2023 Sep;20(9):e17-e91. doi: 10.1016/j.hrthm.2023.03.1538. Epub 2023 May 20.
- 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.
- Sieniewicz BJ, Gould J, Porter B, Sidhu BS, Teall T, Webb J, Carr-White G, Rinaldi CA. Understanding non-response to cardiac resynchronisation therapy: common problems and potential solutions. Heart Fail Rev. 2019 Jan;24(1):41-54. doi: 10.1007/s10741-018-9734-8.
- Burri H, Jastrzebski M, Cano O, Curila K, de Pooter J, Huang W, Israel C, Joza J, Romero J, Vernooy K, Vijayaraman P, Whinnett Z, Zanon F. EHRA clinical consensus statement on conduction system pacing implantation: endorsed by the Asia Pacific Heart Rhythm Society (APHRS), Canadian Heart Rhythm Society (CHRS), and Latin American Heart Rhythm Society (LAHRS). Europace. 2023 Apr 15;25(4):1208-1236. doi: 10.1093/europace/euad043.
- Upadhyay GA, Jastrzebski M, Foley P, Chandrasekaran B, Whinnett Z, Schaller RD, Gardas R, Richardson T, Moskal P, Kudlik D, Stadler RW, Zimmerman P, Burrell J, Waxman R, Cornelussen RN, Lyne J, Herweg B, Vijayaraman P. Echocardiographic response from left bundle branch area pacing optimized cardiac resynchronization therapy (LOT-CRT) vs traditional CRT. Heart Rhythm. 2025 Oct;22(10):2616-2624. doi: 10.1016/j.hrthm.2025.04.026. Epub 2025 Apr 18.
- Chen X, Li X, Bai Y, Wang J, Qin S, Bai J, Wang W, Liang Y, Chen H, Su Y, Ge J. Electrical Resynchronization and Clinical Outcomes During Long-Term Follow-Up in Intraventricular Conduction Delay Patients Applied Left Bundle Branch Pacing-Optimized Cardiac Resynchronization Therapy. Circ Arrhythm Electrophysiol. 2023 Sep;16(9):e011761. doi: 10.1161/CIRCEP.122.011761. Epub 2023 Aug 14.
- Parale C, Bootla D, Jain A, Satheesh S, Anantharaj A, Ahmed AS, Sukumaran SK, Balaguru S, Selvaraj R. Comparison of electrocardiographic parameters between left bundle optimized cardiac resynchronization therapy (LOT-CRT) and left bundle branch pacing-cardiac resynchronization therapy (LBBP-CRT). Pacing Clin Electrophysiol. 2023 Aug;46(8):840-847. doi: 10.1111/pace.14793. Epub 2023 Jul 21.
- Jastrzebski M, Foley P, Chandrasekaran B, Whinnett Z, Vijayaraman P, Upadhyay GA, Schaller RD, Gardas R, Richardson T, Kudlik D, Stadler RW, Zimmerman P, Burrell J, Waxman R, Cornelussen RN, Lyne J, Herweg B. Multicenter Hemodynamic Assessment of the LOT-CRT Strategy: When Does Combining Left Bundle Branch Pacing and Coronary Venous Pacing Enhance Resynchronization?: Primary Results of the CSPOT Study. Circ Arrhythm Electrophysiol. 2024 Nov;17(11):e013059. doi: 10.1161/CIRCEP.124.013059. Epub 2024 Oct 23.
- Vijayaraman P. Left Bundle Branch Pacing Optimized Cardiac Resynchronization Therapy: A Novel Approach. JACC Clin Electrophysiol. 2021 Aug;7(8):1076-1078. doi: 10.1016/j.jacep.2021.04.005. Epub 2021 Jul 28. No abstract available.
- Glikson M, Burri H, Abdin A, Cano O, Curila K, De Pooter J, Diaz JC, Drossart I, Huang W, Israel CW, Jastrzebski M, Joza J, Karvonen J, Keene D, Leclercq C, Mullens W, Pujol-Lopez M, Rao A, Vernooy K, Vijayaraman P, Zanon F, Michowitz Y, Nielsen JC, Boersma L, Blomstrom-Lundqvist C, Kronborg MB, Chung MK, Tse HF, Khan HR, Leyva F, Rojel-Martinez U, Rucinski M, Varma N. European Society of Cardiology (ESC) clinical consensus statement on indications for conduction system pacing, with special contribution of the European Heart Rhythm Association of the ESC and endorsed by the Asia Pacific Heart Rhythm Society, the Canadian Heart Rhythm Society, the Heart Rhythm Society, and the Latin American Heart Rhythm Society. Europace. 2025 Mar 28;27(4):euaf050. doi: 10.1093/europace/euaf050.
- Jastrzebski M, Moskal P, Huybrechts W, Curila K, Sreekumar P, Rademakers LM, Ponnusamy SS, Herweg B, Sharma PS, Bednarek A, Rajzer M, Vijayaraman P. Left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT): Results from an international LBBAP collaborative study group. Heart Rhythm. 2022 Jan;19(1):13-21. doi: 10.1016/j.hrthm.2021.07.057. Epub 2021 Jul 30.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- Clinica CardioVID
- ERP -2025-14209 (Annet stipend/finansieringsnummer: Medtronic)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
Individual participant data, appropriately anonymized, that support the reported results will be made available to qualified researchers for the purposes of scientific research or meta-analysis. Requests must be addressed to the Principal Investigator and include a formal proposal. All requests will be subject to approval by the institutional ethics committee. As this is a study with a small sample size (10 patients), the protocol strictly enforces confidentiality; therefore, prior approval is always required to share these data.
The data will be available from 6 months to 5 years following the publication of the main results.
IPD-delingstidsramme
Tilgangskriterier for IPD-deling
IPD-deling Støtteinformasjonstype
- STUDY_PROTOCOL
- SEVJE
- CSR
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