Conduction System Pacing vs. Biventricular Pacing for Cardiac Resynchronization Therapy (Nordic-CSP)

Nordic-CSP - a Randomized Nordic Study - Is Conduction System Pacing Superior Compared to Conventional BIV-CRT in Reducing the Death or Heart Failure-related Hospitalization in Patients With Heart Failure and Bundle Branch Block?

The NORDIC-CSP trial is an investigator-initiated, blinded, nordic RCT aimed at evaluating whether using direct pacing of the HIS bundle (HIS)-pacing or left bundle branch (LBB) pacing is superior to conventional biventricular pacing in reducing the incidence of the composite endpoint of death and non-planned HF hospitalization. The study will be conducted in the 4 CRT-centres in Denmark and 6-8 centres from countries Sweden, Norway and Finland.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure; Conduction System Pacing; Cardiac Resynchronisation Therapy (CRT)
• Intervention / Treatment: Procedure: HIS or LBBB -CRT; Procedure: Conventional BiV-CRT

Detailed Description

In this investigator-initiated, blinded, nordic RCT, we will investigate conduction system pacing (CSP) in heart failure (HF) patients. We hypothesized that Cardiac Resynchronization Therapy (CRT) by HIS-pacing or LBB-pacing is superior compared to conventional biventricular (BIV)-CRT in reducing the incidence of the composite endpoint (Death and HF-hospitalization) in patients with symptomatic HF, with LVEF ≤ 35% and indication for CRT.

The Study is a collaboration between CRT centers in the Nordic countries with experience in CSP.

Randomization:

Randomization is conducted electronically using the CRF on the day of device implantation. A computer algorithm will randomly assign patients 1:1 to either the conventional method BIV-CRT or to "the new method" HIS/LBB-CRT.

Randomization will be stratified by the presence of a) true LBBB, b) other bundle branch block (BBB) and c) RV pacing. This will be performed by randomizing in blocks of 10 for LBBB and RV pacing/other bundle branch blocks. Block-randomization is used to ensure that each center includes a similar number of patients for each treatment arm.

The implanting physician is aware of group allocation to provide the correct treatment. Only the implanting physician can access this information in the CRF. The patients and study per-sonnel involved in end-point adjudication as well as all personnel performing imaging analy-sis are blinded to randomization. Follow-up is identical in the two treatment groups. All fol-low-up personnel are blinded to treatment assignment.

Implantation:

The RV electrode is preferentially placed in an RV septal position unless factors related to lead stability, electrical values, and defibrillation vector favor an apical position (at the discretion of the implanting physician). The atrial electrode is positioned at the preference of the implanting physician. With successful implantation of a lead for HIS- or LBB-pacing the physician may prefer to not implant a RV-lead to the septum. In that case, there is no need for a CRT pacemaker and a dual-chamber pacemaker can be implanted instead.

In the HIS-LBB group, CSP is performed according to current recommendations13. The leads allowed to implant in the HIS-LBB position are the ones that have received CE-approval for this indication.

Both HIS-pacing or LBB-pacing can be attempted as first approach at the physician's discretion using available leads both stylet-driven or non-stylet driven and if necessary, guiding from an electrophysiology catheter is used.

HIS-pacing: An approximate ratio of 1:4 between A and V with a clear His deflection is iden-tified and His-capture confirmed. If the threshold for capture of His and the left bundle branches is too high (> 2 V at 1 ms duration) assessed by the operator, the lead should be replaced. If it is not possible to achieve selective or non-selective HIS pacing with bundle branch block correction at a threshold below or equal to 2 V at 1 ms in duration, an attempt to implant the electrode to achieve direct left bundle branch pacing (LBBP) is performed instead.

LBB-pacing: LBB-pacing is performed by moving the sheath a few centimeter further towards the apex of the right ventricle, ensuring contact to the septum. The electrode is screwed into the septum at an angle of -10⁰ to 40⁰ while monitoring current-of-injury (COI), impedance and pacing configuration (gradual emergence of a terminal R-wave in lead V1) until the left bundle branch area is activated and a right-sided bundle branch block pattern is obtained. The operator must attempt to confirm left conduction system capture by identify-ing one or more of the following criteria:

• Fixation beats (PVC´s identical to the paced QRS-complex,)
• Identification of LBB-potentials (> 15 ms before sensed QRS) and capture with RBBB-pattern during unipolar pacing on the LBB-lead. (Not in LBBB patients)
• Transition of QRS patterns during threshold testing:

ns-LBBP to s-LBBP : splitting of EGM and/or V1 RWPT (Rigth wave peak time)¬ by > 10 ms ns-LBBP to LVSP : V6 RWPT¬ by ≥ 15 ms V6 RWPT < 80 ms (LBBB, IVCD RBBB+fascicular block, wide escape rhythm, asystole) V6 -V1 interpeak interval > 44 ms QRS transition to s-LBBP during programmed stimulation

Or one of the following criteria considered likely to represent left conduction system capture:

V6 RWPT < 100 ms (LBBB, IVCD, RBBB + fascicular block, wide escape rhythm, asystole V6 -V1 interpeak interval > 33 ms QRS transition to LVSP during programmed stimulation V6 RWPT prolongation by 10-14 ms during threshold test

If the operator is not succesful, after several attempts, obtaining conduction system capture LVseptal capture (LVSP) can be accepted, with identification of a clearly defined R´ in V1. If only deep septal pacing can be obtained the lead can be left in place or removed at the op-erators discretion and an LV-lead has to be implanted to obtain either BIV-CRT or LOT-CRT.

.

Cross-over between intervention arms If neither HIS-pacing nor LBB-pacing is obtainable (none of the abovementioned criteria are met or Left Ventricular septal pacing cannot be obtained), the sheath is switched to a CS sheath instead and an LV electrode is placed as in a conventional CRT procedure. Finally, an atrial electrode is placed if there is not already a usable atrial electrode in place. In all pa-tients, signs of left conduction system capture identified are registered in the CRF.

In the BIV-CRT group, the LV lead is placed in the branch judged to be most suitable, prefer-entially in a posterolateral (2-5 o'clock in the mitral annulus), and mid-ventricular or basal, non-apical position (figure 2), after taking into consideration lead stability, pacing threshold and threshold for phrenic nerve stimulation. In general, multipolar (quadripolar) LV leads are used as first choice but the implanting physician may use a bipolar LV lead if a multipolar lead cannot be implanted. Balloon occlusion venography to visualize the CS and side branches is performed in all patients with a BIV-CRT. Supplementary selective venography may be used to visualize CS branches.

If it is not possible to place a LV -lead due to the anatomical conditions (lack of access to CS, lack of available side bundle branches or only possible to pace in the vena cordis media or vena cordis anterior) or due to unacceptable electrical measurements (best pacing threshold > 4 V at 1,0 msec, or phrenic nerve capture < 2 x lowest pacing threshold), the sheath is in-stead switched to a HIS sheath and electrode placement to the HIS bundle or LBB area is attempted using available sheaths and guide from electrophysiology catheter as outlined above. Again, it is up to the physician whether HIS- or LBB-pacing is attempted first. If it is not possible to achieve selective or non-selective HIS pacing with bundle branch block cor-rection at a threshold below or equal to 2.5 V at 1 ms in duration, an attempt is done to im-plant the electrode further into the ventricle and achieve direct left bundle branch pacing (LBB-CRT) instead. Finally, an atrial electrode is placed if there is not already a usable atrial lead in place. If it is not possible to place either an LV electrode, a HIS electrode or an elec-trode for LBB pacing, the attending physician must decide whether there is any indication for implantation of a transthoracic LV-lead.

Follow-up:

Clinical- and device check-ups are scheduled after 3-, 6- and 12 months, and annually thereafter according .This means that patients are in fact following the current standard regime after CRT-implantation with similar examinations including standard blood tests. However, in addition the patients will be asked to fill out questionnaires, that is the MLHFQ and PRO Questionnaires at baseline and 12 months. Remote monitoring is established for all pa-tients. Echocardiographic follow-ups are scheduled after 6- and 24 months. A 6MWT is per-formed 6 months. At each follow-up visit, medication is recorded and a ECG-12 is obtained upon patient arrival.

All patients are followed for a minimum of 2 years.

• Study Type: Interventional
• Enrollment (Estimated): 1100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Niels Risum, MD, PhD; Phone Number: 0045 35456995; Email: niels.risum.01@regionh.dk
• Study Contact Backup: Name: Michael Vinther, MD, PhD; Phone Number: 0045 35456994; Email: michael.vinther@regionh.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Dept. of Cardiology, Aarhus University Hospital, Aarhus
    • Contact: Jens Kristensen, MD, PhD; Phone Number: 0045 29410644; Email: jens.kristensen@auh.rm.dk
• Finland
  • Helsinki, Finland, 00290
    • Dept of Cardiology, Meilahti Hospital, Helsinki
    • Contact: Jarkko Karvonen Karvonen; Email: jarkko.karvonen@hus.fi
• Norway
  • Bergen, Norway, 5009
    • Haukeland Universitetssykehus
    • Contact: Torbjørn Lunde; Phone Number: 0047 xxxxxxxx; Email: torbjorn.lunde@gmail.com
• Sweden
  • Gothenburg, Sweden
    • Sahlgrenska University Hospital
    • Contact: Amar Taha; Phone Number: 0046 313427551; Email: Amar.taha@vregionh.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥18 years of age,
• LVEF ≤ 35%,
• NYHA Class II-IV (IV only outpatients),
• optimized in medical treatment (OMT)

AND one of the following:

. LBBB according to AHA/ACC/HRS Scientific Statement from 2009 and ≥130ms or

• LBBB-like intraventricular conduction delay (IVCD) > 150ms or RV paced QRS and indication for upgrade to CRT (> 40% RV pacing) OR
• ≥18 years of age,
• LVEF ≤ 40 %
• pacing indicated by AV-block and, thus, expected large percentage of ventricular pacing.

Exclusion Criteria:

• recent acute myocardial infarction (AMI)
• coronary artery bypass graft (CABG) (<3 months)
• life expectancy <2 years, patients in hemodialysis
• treatment with a cardiac implantable electronic device (CIED) is contraindicated.
• Patients are excluded with regards to the MRI sub study if eGFR > 35 ml/min, in case or contrast allergy or certain metal implants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LBB/HIS-CRT group	Procedure: HIS or LBBB -CRT; HIs pacing og LBB pacing at the implanteres discretion
Experimental: BiV-CRT group	Procedure: Conventional BiV-CRT; An LV-lead in a side-branch of the coronary sinus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients with a primary end-point	The primary endpoint is a composite of time to death or first non-planned HF hospitalization. Non-planned HF is defined as an unplanned emergency room visit or admission to hospital due to worsening HF	From enrollment and a minimum of 2 years or the primary outcome has occurred

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients experiencing device-related complications	• Device-related complications. Periprocedural complication including electrode reoperation, pneumothorax, hemothorax, pericardial bleeding/tamponade and later complications (after 30 days post implantation) including LV/His electrode reoperation, change of device due to battery depletion and infection requiring extraction.	From baseline until study completion, with a minimum of 2 years.
Death	All-cause death	From baseline until study completion, with a minimum of 2 years
Non planned HF-hospitalization	Non-planned HF is defined as an unplanned emergency room visit or admission to hospital due to worsening HF	From baseline until study completion with a minimum of 2 years
Echocardiographic remodelling	Echocardiographic end-points (re-modelling of the LV measured in mL: LVESV, LVEDV, LVEF). Echocardiographic response after 6 months and 24 months defined as decrease in left ventricular systolic volume ≥ 15% from baseline.	From baseline to 6 months and 24 months
Change in Dyssynchrony	Change in dyssynchrony parameters myocardial work, longitudinal strain time-to-peak (ms), dyssynchrony patterns (categorized 1-4), apical rocking, septal flash (yes/No)	evaluated at baseline, 6 months, 24 months
Improvement in Clinical response	Clinical response improvement in NYHA class by ≥ 1 or improvement in 6MWT (≥10% from baseline)" after 12 months.	from baseline to 12 months
Improvement in Six-min walking test.	Functional response after 6 months defined as an increase in 6-min walking distance (meters) of ≥ 20% of the baseline value	From baseline to 6 months
Neurohormones	Neurohormones, decline in NT-proBNP after CRT. pg/mL (picograms per milliliter) or ng/L (nanograms per liter)	from baseline to 6 months
Symptomatic response	defined as a fall in NYHA class of ≥ 1	From baseline to 6 months
Life quality	Minnesota Living with Heart Failure Qestionnaire. Comparison from baseline to 12 months follow-up in point score (0-105). Number of patients with improvements > 5 points and above 10 points are determined.	from baseline to follow-up at 12 months
ICD therapy	ICD-therapy (time to first) of appropriate and inappropriate therapies, ATP or Shock	from baseline to study completion, with a mnimum of 2 years
Ventricular arrythmia	Time to first VT (>135/min by ecg or device reading) or VF	from baseline to completion of the study, with a mnimum of 2 years
atrial fibrillation	time to Persistent atrial fibrillation (> 7 days) and new-onset atrial fibrilllation (> 6 hours)	from baseline to completion of the study with a minimum of 2 years
time for implantation	measured in minutes from skin incision to skin closure	at implantation, from 30 minutes to 300 minutes
x-ray	• Use of X-ray dosage	at implantation, from 1 minute to 150 minutes
Electrodes	number of electrodes used	form implantation to completion of the study, a minimum of 2 years
battery longevity	• Battery longevity: The total battery longevity of each CRT-D was calculated as the sum of the patient's follow-up duration plus the estimated battery longevity remaining at the time of the last follow-up.	from implantation to completion of the study, with a minimum of 2 years

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Niels Risum Risum, MD, PhD, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Principal Investigator: michael vinther, MD, PhD, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Study Chair: Berit Philbert, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): March 1, 2031
• Study Completion (Estimated): July 1, 2031

Study Registration Dates

• First Submitted: February 10, 2026
• First Submitted That Met QC Criteria: March 20, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cardiac Resynchronization Therapy; conduction system pacing; Biventricular pacing; LBB-pacing; His-pacing; Nordic-CSP
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: 119231

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: not yet a plan for this

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No