Arrhythmias, CardiacTREEBEARDNCT06324682
ConTempoRary Cardiac Stimulation in Clinical practicE: lEft, BivEntriculAr, Right, and conDuction System Pacing
An observational study of Arrhythmias, Cardiac and Atrioventricular Block, run by University Hospital of Ferrara at 31 sites in Italy.
Trial summary
The goal of this observational study is to evaluate the clinical characteristics of patients undergoing permanent cardiac pacing and to compare procedural efficacy and safety of different implantation approaches in the clinical practice of the participating centres. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Arrhythmias, Cardiac, Atrioventricular Block, Reduced Systolic Function
- What is being tested?
- Cardiac pacing - Conventional RV pacing, Cardiac pacing - Conduction System Pacing and Cardiac pacing - Cardiac resynchronization therapy (pacing - CRTP - or defibrillation - CRTD)
- Type of treatment
- Injection or infusion, Medical device
- How many people
- 8,400 participants
- Where
- 31 sitesItaly
- Study dates
- 1 Jan 2023to 31 Dec 2034
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with an indication for permanent cardiac stimulation who have subsequently undergone an implantation procedure for an implantable electronic device at the Electrophysiology Laboratories of participating centers within a period of 120 months from the time of approval, with a corresponding follow-up period of another 120 months.
Who may be able to join
- Indication for cardiac stimulation
- Having performed the implantation of a device for cardiac stimulation
Who cannot join
- Age < 18 years;
- Pregnancy status;
Trial locations and contacts
31 sites in 1 country. Contact the study team or a site near you to ask about taking part.
31 sites in 1 country
Italy31 sites, 31 recruiting
- Recruiting
Ospedale San Donato
Arezzo
Pasquale Notarstefano, MD
- Recruiting
Azienda Ospedaliero-Universitaria S.Orsola-Malpighi Bologna
Bologna, 40138
Mauro Biffi, MD
- Recruiting
spedale Maggiore di Bologna
Bologna
Valeria Carinci, MD
- Recruiting
Ospedale Bernardino Ramazzini
Carpi
Elia De Maria, MD
- Recruiting
Ospedale SS Annunziata
Cento
Biagio Sassone, MD
- Recruiting
Ospedale Bufalini
Cesena
Paolo Sabbatani, MD
- Recruiting
Ospedale San Giuseppe
Empoli
Attilio Del Rosso, MD
- Recruiting
Azienda Ospedaliero-Universitaria di Ferrara
Ferrara, FE, 44124
Matteo Bertini, MD, PhD, +390532236269, brtmtt2@unife.it
- Recruiting
Ospedale di Vaio
Fidenza
Paolo Pastori
- Recruiting
Azienda Ospedaliero-Universitaria Careggi
Florence
Giuseppe Ricciardi, MD
- Recruiting
Ospedale San Giovanni di Dio
Florence
Iacopo Bertolozzi, MD
- Recruiting
Ospedale Santa Maria Annunziata Bagno a Ripoli
Florence
Maria Giaccardi, MD
- Recruiting
Azienda Ospedaliero-Universitaria "Ospedali Riuniti"
Foggia
Pier Luigi Pellegrino, MD
- Recruiting
Ospedale Morgagni-Pierantoni
Forlì
Alberto Bandini, MD
- Recruiting
Ospedale Santa Maria della Misericordia Grosseto
Grosseto
Gennaro Miracapillo, MD
- Recruiting
Ospedale della Versilia
Lido di Camaiore
Gianluca Solarino, MD
- Recruiting
Ospedali Riuniti di Livorno
Livorno
Federica Lapira, MD
- Recruiting
Ospedale San Luca
Lucca
Davide Giorgi, MD
- Recruiting
Nuovo ospedale Apuano Massa
Massa
Giuseppe Arena, MD
- Recruiting
Azienda Ospedaliero-Universitaria Policlinico di Modena
Modena
Giuseppe Boriani, PhD
- Recruiting
Ospedale Sant'Agostino Estense Modena Baggiovara
Modena
Mauro Zennaro, MD
- Recruiting
Ospedale Civico, azienda Ospedaliera di Palermo
Palermo
Giuseppe Sgarito, MD
- Recruiting
Policlinico Paolo Giaccone
Palermo
Giuseppe Coppola, MD
- Recruiting
Azienda Ospedaliero-Universitaria Maggiore
Parma
Francesca Maria Notarangelo, MD
- Recruiting
Ospedale Guglielmo da Saliceto Piacenza
Piacenza, 29100
Luca Rossi, MD
- Recruiting
Azienda Ospedaliero-Universitaria pisana Cisanello
Pisa
Giulio Zucchelli
- Recruiting
Fondazione Toscana Gabriele Monasterio
Pisa
Andrea Rossi, MD
- Recruiting
Ospedale Santa Maria delle Croci
Ravenna
Alessandro Dal Monte
- Recruiting
ASMN Reggio Emilia
Reggio Emilia
Fabio Quartieri, MD
- Recruiting
Ospedale degli Infermi Rimini
Rimini
Davide Saporito, MD
- Recruiting
Azienda Ospedaliero-Universitaria Senese
Siena
Amato Santoro, MD
About this study
Official title: Evaluation of conTempoRary Cardiac Stimulation in Clinical practicE: lEft, BivEntriculAr, Right, and conDuction System Pacing
The goal of this observational study is to evaluate the clinical characteristics of patients undergoing permanent cardiac pacing and to compare procedural efficacy and safety of different implantation approaches in the clinical practice of the participating centres. The contribution of non-fluoroscopic anatomical and electrophysiological reconstruction systems to device implantation procedures will also be evaluated.
Participants [patients over 18 years old with an indication to receive a definitive pacemaker/intracardiac defibrillator implant] will receive a permanent cardiac pacing implant as requested according to European Society of Cardiology (ESC) guidelines; the investigators will evaluate procedural efficacy and safety of different implantation approaches.
Read the detailed description
Cardiac pacing with implantable electronic cardiac devices and transvenous leads has been introduced since 1960 and is considered a safe, effective and low-risk therapy. The most common indications for permanent cardiac pacing are sinus node dysfunction and atrioventricular blocks. In Europe, pacemaker implants exceed 1000 per million inhabitants. The aim of this therapy is not only to improve patients survival but also their quality of life, which is an essential aspect in assessing patients clinical status and prognosis.
Nowadays, five types of cardiac pacing are recognised in clinical practice:
- Endocardial right chambers pacing: the device is implanted in the subcutaneous subclavian area and it is connected to transvenous leads implanted in the right cardiac chambers, which detect intrinsic electrical activity and stimulate when needed;
- Epicardial pacing: this procedure is often performed in conjunction with cardiac surgery;
- Cardiac resynchronisation therapy (CRT): it delivers biventricular or left ventricular pacing in order to correct interventricular electromechanical dyssynchrony and to improve cardiac output;
- Conduction system pacing: it stimulates the His bundle or the left bundle branch area downstream of the conduction block, in order to restore a physiological electromechanical activation.
- Leadless pacing: via a percutaneous approach through a large-calibre vein, leadless device is placed inside the right ventricle.
These pacing modalities have different possibilities to restore a normal cardiac electromechanical activation, resulting in different degrees of mechanical efficiency in terms of systolic output and diastolic pressures, with consequent effects on improvement/onset of heart failure and cardiopulmonary performance of our patients.
Right ventricular pacing induces a dyssynchronous cardiac activation pattern that can lead to left systolic dysfunction and a consequent increased risk of death related to the development of heart failure.
These observations led to the study of alternative cardiac pacing modalities since the 1990s, in order to improve the clinical outcome of patients with symptomatic bradyarrhythmias. The study of pathological ventricular activation due to left bundle-branch block represents the pathophysiological premise of cardiac resynchronisation in patients with systolic dysfunctional heart failure, and constitutes the developmental model for physiological pacing.
CRT improves mortality and quality of life in patients with heart failure and reduced left ventricular ejection fraction. Typically left ventricular pacing is achieved by placing a catheter in the posterolateral area through a venous branch of the coronary sinus. Unfortunately, despite several years of experience in this field, clinical non-response to this therapy is observed in between 20% and 40% of patients, mostly due to the inability to reach the appropriate pacing site because of anatomical difficulties/absence of veins in the target area.
Recently, conduction system pacing (CSP) has rapidly emerged as an alternative pacing modality to both right ventricular pacing (RVP) and CRT, in order to achieve a more physiological pacing. His bundle pacing (HBP) is considered the physiological pacing "par excellence", but the results in literature show rather frequent technical difficulties due to high pacing thresholds, inadequate ventricular signal amplitude for the detection of intrinsic cardiac activity, low success rate and risk of progression of conduction system pathology in patients with infranodal conduction defects.
Left bundle area pacing has more recently emerged as a viable alternative to achieve physiological pacing with haemodynamic parameters similar to those of HBP, but with lower and stable pacing thresholds, ventricular signal amplitude adequate for the detection of intrinsic cardiac activity and high success rate.
Several experiences with different pacing systems have been published, mainly single-centre studies with small sample sizes and different definitions of conduction system pacing success.
In non-randomised comparative studies, and thus with methodological limitations, clinical superiority over conventional right ventricular pacing, and a substantial efficacy equivalent to CRT in patients with left bundle-branch block, has been shown, creating the preconditions for widespread use of the CSP.
Considering, therefore, the widespread use of the latter technique and the high rate of implants that can potentially benefit from physiological pacing, evaluating safety, feasibility, timing and benefits becomes more crucial than ever.
Therefore, the goal of this observational study is to evaluate the clinical characteristics of patients undergoing permanent cardiac pacing and to compare procedural efficacy and safety of different implantation approaches in the clinical practice of the participating centres.
The contribution of non-fluoroscopic anatomical and electrophysiological reconstruction systems to device implantation procedures will also be evaluated.
The investigators will collect clinical and procedural data from patients with an indication for permanent cardiac pacing who have consecutively undergone an implantable electronic device implant procedure at the Electrophysiology Laboratories of the participating centres over a period of 120 months from the time of approval with a follow-up of an equal 120 months.
Patients will be classified according to the type of stimulation:
- Right chambers endocardial pacing;
- Cardiac resynchronisation therapy;
- Conduction system pacing:
- His bundle pacing
- Left bundle branch area pacing. In addition, the efficacy and safety at 30 days, and the efficacy and safety at 6 and 12 months of the various pacing modalities, will be evaluated.
The investigators defined efficacy at 30 days the presence of stable electrical parameters - or, if unstable, not requiring early re-intervention, the absence of cardiovascular hospitalizations and the absence of cardiovascular death.
The investigators defined safety at 30 days the absence of procedural complications, such as haematoma requiring re-intervention or with haemoglobin loss >2gr/dl, pneumothorax, pericardial effusion requiring drainage, lead dislocation, cardiac implantable electronic device (CIED) infection or a re-intervention for any cause.
Equally, the investigators defined efficacy at 6-12 months the presence of stable electrical parameters - or, if unstable, not requiring re-intervention, the absence of cardiovascular hospitalizations, the absence of cardiovascular death, the occurrence of heart failure, the occurrence or worsening of atrial or ventricular tachyarrhythmias.
Therefore, the investigators defined safety at 6-12 months the proper functioning of the device, the absence of infection and the absence of re-intervention for any cause.
- Conditions
- Arrhythmias, Cardiac, Atrioventricular Block, Reduced Systolic Function, Atrial Fibrillation, Bradyarrhythmia, Ventricular Tachycardia
- Being tested
- Cardiac pacing - Conventional RV pacing, Cardiac pacing - Conduction System Pacing, Cardiac pacing - Cardiac resynchronization therapy (pacing - CRTP - or defibrillation - CRTD), Cardiac pacing - Epicardial pacing, Cardiac pacing - Leadless pacing
- Keywords
- Pace maker (PM), Implantable cardioverter defibrillator (ICD), Atrioventricular Block, Bradyarrhythmia, Ventricular Dysfunction, Cardiac Resynchronization therapy, Conduction System Pacing, His Pacing, Left bundle branch area pacing (LBBAP), CRT, CSP, Primary prevention, Secondary prevention, Atrioventricular Block Complete, Heart failure, Ventricular Arrythmia, Ventricular Fibrillation, Ventricular Tachycardia
- Medical subject headings
- Arrhythmias, Cardiac, Atrioventricular Block, Atrial Fibrillation, Bradycardia, Tachycardia, Ventricular, Ventricular Dysfunction, Ventricular Fibrillation, Bundle-Branch Block
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiac pacing - Conventional RV pacingDevice
Also called Cardiac defibrillation - Conventional RV pacing
Implantation of devices for cardiac pacing/defibrillation
Cardiac pacing - Conduction System PacingDevice
Also called Cardiac defibrillation - Conduction System Pacing
Implantation of devices for cardiac pacing/defibrillation
Cardiac pacing - Cardiac resynchronization therapy (pacing - CRTP - or defibrillation - CRTD)Device
Also called Cardiac defibrillation - Cardiac resynchronization therapy (pacing - CRTP - or defibrillation - CRTD)
Implantation of devices for cardiac pacing/defibrillation
Cardiac pacing - Epicardial pacingDevice
Also called Cardiac defibrillation - Epicardial pacing
Implantation of devices for cardiac pacing/defibrillation
Cardiac pacing - Leadless pacingDevice
Also called Cardiac defibrillation - Leadless pacing
Implantation of devices for cardiac pacing/defibrillation
| Study group | Role | What they receive |
|---|---|---|
| Conventional right ventricular (RV) pacing | The device (pace maker or implantable cardiac defibrillator) is implanted in the subcutaneous subclavian area (right or left) and it is connected to transvenous lead/leads (active or passive) implanted in the right cardiac chambers (atrium and ventricle or ventricle only), which detect intrinsic electrical activity and stimulate when needed. The ventricle pacing might be obtained with an apical or septal stimulation.
Vascular access might be from the cephalic, axillary or subclavian veins. Once positioned, lead's pacing threshold, sensing and impedance are measured. If the investigators find good and stable electrical parameters, the catheter(s) is(are) fixed and left in place. Receives: Device: Cardiac pacing - Conventional RV pacing | |
| Conduction System Pacing | The approach for the insertion of the device and of the transvenous leads is similar to the previous ones.
The ventricle activation might be obtained with the his bundle stimulation or with the left bundle branch area pacing downstream of the conduction block. Vascular access might be from the cephalic, axillary or subclavian veins.
Both selective and non-selective stimulation of the His bundle and the stimulation of the left bundle branch and left septum are considered successful. In both cases, attempts are made to locate the atrio-ventricular junction by fluoroscopic methods or with three-dimensional electroanatomical mapping system. The Hisian potential is sought and the catheter is positioned. In the LBBAP the investigators place the lead 1.5 cm below the His region and, with the pacemaking method, the investigators identify an area that electrocardiographically shows a W signal in V1 lead with D2 more positive than D3 - after checking the electrical parameters. Receives: Device: Cardiac pacing - Conduction System Pacing | |
| Cardiac resynchronization therapy (CRT) either -pacing (CRTP) or -defibrillation (CRTD) | The approach for the insertion of the device and of the transvenous leads is similar to the previous ones.
The right ventricle pacing (with a pacing lead or a defibrillation coil) might be obtained with an apical or septal stimulation, while the left ventricular pacing is achieved by placing a catheter (active or passive) in the posterolateral area through a venous branch of the coronary sinus.
Cardiac resynchronisation therapy (CRT) delivers biventricular or left ventricular only pacing.
Vascular access might be from the cephalic, axillary or subclavian veins. Once positioned, lead's pacing threshold, sensing and impedance are measured. If the investigators find good and stable electrical parameters, the catheter(s) is(are) fixed and left in place - paying attention to the phrenic nerve capture threshold. Receives: Device: Cardiac pacing - Cardiac resynchronization therapy (pacing - CRTP - or defibrillation - CRTD) | |
| Epicardial pacing | The device is usually placed in the subcutaneous abdominal area and the lead(s) is(are) secured in the epicardial surface. It is often used in congenital heart defects or post-cardiac surgery scenarios.
Surgeons may access the epicardium during open-heart surgery or with minimally invasive techniques. Receives: Device: Cardiac pacing - Epicardial pacing | |
| Leadless pacing | The leadless device is placed via a percutaneous approach through a large-calibre (femoral) vein inside the right ventricle. It is suitable for patients needing a single chamber pacing such as patients with permanent atrial fibrillation with slow ventricular response, in some cases of paroxysmal atrioventricular block, or patients with a history of CIED infections.
The only one currently available has a cardiac muscle fixation system consisting of 4 self-expanding barbs.
Once positioned, pacing threshold, sensing and impedance are measured. If the investigators find good and stable electrical parameters, the catheter is left in place. Receives: Device: Cardiac pacing - Leadless pacing |
What is being measured
The primary outcome is the main question the study is designed to answer.
30 days efficacy
Number of successful implantations, defined as the achievement of the planned pacing modality
Measured: 30 days
Rate of hospitalizations for heart failure at 12 months
The investigators considered the worsening of heart failure requiring hospital management
Measured: 12 months
All cause death at 12 months
The investigators will monitor patient's all causes death
Measured: 12 months
Secondary outcomes (17)
All cause and cardiovascular death at 1, 3, 5, 10 years
The investigators will monitor patient's all causes and cardiovascular death
Measured: 120 months
Onset/worsening of heart failure
The investigators will assess patient's hemodynamic stability over the years, monitoring the onset or the worsening of heart failure
Measured: 120 months
Onset/worsening of atrial tachyarrhythmias
The investigators will monitor patient's rhythm over the years, assessing the onset or the worsening of atrial tachyarrhythmias.
Measured: 120 months
Onset/worsening of ventricular tachyarrhythmias
The investigators will monitor patient's rhythm over the years, assessing the onset or the worsening of ventricular tachyarrhythmias.
Measured: 120 months
Procedural time
The investigators will evaluate procedural time of different cardiac pacing modalities
Measured: implantation procedure
Fluoroscopy time
The investigators will evaluate fluoroscopy time of different cardiac pacing modalities
Measured: implantation procedure
Radiation exposure
The investigators will evaluate radiation exposure of different cardiac pacing modalities monitoring the dose area product
Measured: implantation procedure
Success rate of CRT in heart failure
The investigators consider successful CRT if obtain a left ventricular end-systolic volume reduction >15%
Measured: 120 months
Cardiac perforation rate
The investigators will evaluate how often cardiac perforation occurs in relation to the total number of implants and in the various pacing modalities
Measured: 30 days
Hemothorax rate
The investigators will evaluate how often hemothorax occurs in relation to the total number of implants and in the various pacing modalities
Measured: 30 days
Pneumothorax rate
The investigators will evaluate how often pneumothorax occurs in relation to the total number of implants and in the various pacing modalities
Measured: 30 days
Pocket hematoma rate
The investigators will evaluate how often pocket hematoma occurs in relation to the total number of implants and in the various pacing modalities
Measured: 30 days
Pericardial effusion rate
The investigators will evaluate how often pericardial effusion occurs in relation to the total number of implants and in the various pacing modalities
Measured: 30 days
Lead dislocation rate
The investigators will evaluate how often catheter dislocation occurs in relation to the total number of implants and in the various pacing modalities
Measured: 120 months
Lead fracture rate
The investigators will evaluate how often catheter rupture occurs in relation to the total number of implants and in the various pacing modalities
Measured: 120 months
Cardiac Implantable Electronic Devices infections rate
The investigators will evaluate how often infections occur in relation to the total number of implants and in the various pacing modalities
Measured: 120 months
Reintervention rate
The investigators will evaluate how often reintervention is needed in relation to the total number of implants and in the various pacing modalities
Measured: 120 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2024
- Study start1 Jan 2023
- Primary completion31 Dec 2033 (estimated)
- Study completion31 Dec 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Arrhythmias, CardiacStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 8,400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital of Ferrara
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matteo Bertini, University Hospital of Ferrara
- Investigators
- Matteo Bertini, MD, PhD, Principal investigator, Azienda Ospedaliero Universitaria di Ferrara
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06324682
- Sponsor's protocol ID
- 825/2022/Oss/AOUFe
- Acronym
- TREEBEARD
- Status last verified
- Mar 2024
- First submitted
- 31 Jan 2024
- Last updated
- 22 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Bertini M, Canovi L, Vitali F, Marcantoni L, Pastore G, Volpicelli M, Munciguerra O, Biffi M, Ziacchi M, Rossi L, Carinci V, Sirugo P, Pastori P, Imberti JF, Pellegrino PL, Guerriero E, Sassone B, Bertagnin E, Coppola G, Malagu M, Balla C, Azzolini G, Zuccari G, Zanon F, Boriani G, Zuin M. Two-year outcomes of left bundle branch area pacing versus traditional right ventricular pacing in middle-aged adults: a registry-based trial. Europace. 2025 Aug 4;27(8):euaf181. doi: 10.1093/europace/euaf181.
PubMed 40880214Bertini M, Vitali F, Malagu M, Azzolini G, Clo S, Canovi L, Farina J, Bianchi N, De Raffele M, Bianchi C, De Pietri M, Guidi Colombi G, Micillo M, Melpignano A, Pavasini R, Balla C, Guardigli G, Vijayaraman P, Zuin M. Left Ventricular Mechanical Insights Into Left Bundle Branch Pacing and Left Ventricular Septal Pacing. JACC Clin Electrophysiol. 2025 Aug;11(8):1852-1861. doi: 10.1016/j.jacep.2025.03.037. Epub 2025 May 28.
PubMed 40439650
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of conTempoRary Cardiac Stimulation in Clinical practicE: lEft, BivEntriculAr, Right, and conDuction System Pacing
- ClinicalTrials.gov ID
- NCT06324682
- Acronym / sponsor ID
- TREEBEARD / 825/2022/Oss/AOUFe
- Conditions
- Arrhythmias, Cardiac, Atrioventricular Block, Reduced Systolic Function, Atrial Fibrillation, Bradyarrhythmia, Ventricular Tachycardia
- Keywords
- Pace maker (PM), Implantable cardioverter defibrillator (ICD), Atrioventricular Block, Bradyarrhythmia, Ventricular Dysfunction, Cardiac Resynchronization therapy, Conduction System Pacing, His Pacing
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 8,400 participants (estimated)
- Lead sponsor
- University Hospital of FerraraUniversity, hospital or other
- Study start
- 1 Jan 2023 (actual)
- Primary completion
- 31 Dec 2033 (estimated)
- Study completion
- 31 Dec 2034 (estimated)
- First posted
- 22 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this observational study is to evaluate the clinical characteristics of patients undergoing permanent cardiac pacing and to compare procedural efficacy and safety of different implantation approaches in the clinical practice of the participating centres. The contribution of non-fluoroscopic anatomical and electrophysiological reconstruction systems to device implantation procedures will also be evaluated.
Participants [patients over 18 years old with an indication to receive a definitive pacemaker/intracardiac defibrillator implant] will receive a permanent cardiac pacing implant as requested according to European Society of Cardiology (ESC) guidelines; the investigators will evaluate procedural efficacy and safety of different implantation approaches.
Detailed description
Cardiac pacing with implantable electronic cardiac devices and transvenous leads has been introduced since 1960 and is considered a safe, effective and low-risk therapy. The most common indications for permanent cardiac pacing are sinus node dysfunction and atrioventricular blocks. In Europe, pacemaker implants exceed 1000 per million inhabitants. The aim of this therapy is not only to improve patients survival but also their quality of life, which is an essential aspect in assessing patients clinical status and prognosis.
Nowadays, five types of cardiac pacing are recognised in clinical practice:
- Endocardial right chambers pacing: the device is implanted in the subcutaneous subclavian area and it is connected to transvenous leads implanted in the right cardiac chambers, which detect intrinsic electrical activity and stimulate when needed;
- Epicardial pacing: this procedure is often performed in conjunction with cardiac surgery;
- Cardiac resynchronisation therapy (CRT): it delivers biventricular or left ventricular pacing in order to correct interventricular electromechanical dyssynchrony and to improve cardiac output;
- Conduction system pacing: it stimulates the His bundle or the left bundle branch area downstream of the conduction block, in order to restore a physiological electromechanical activation.
- Leadless pacing: via a percutaneous approach through a large-calibre vein, leadless device is placed inside the right ventricle.
These pacing modalities have different possibilities to restore a normal cardiac electromechanical activation, resulting in different degrees of mechanical efficiency in terms of systolic output and diastolic pressures, with consequent effects on improvement/onset of heart failure and cardiopulmonary performance of our patients.
Right ventricular pacing induces a dyssynchronous cardiac activation pattern that can lead to left systolic dysfunction and a consequent increased risk of death related to the development of heart failure.
These observations led to the study of alternative cardiac pacing modalities since the 1990s, in order to improve the clinical outcome of patients with symptomatic bradyarrhythmias. The study of pathological ventricular activation due to left bundle-branch block represents the pathophysiological premise of cardiac resynchronisation in patients with systolic dysfunctional heart failure, and constitutes the developmental model for physiological pacing.
CRT improves mortality and quality of life in patients with heart failure and reduced left ventricular ejection fraction. Typically left ventricular pacing is achieved by placing a catheter in the posterolateral area through a venous branch of the coronary sinus. Unfortunately, despite several years of experience in this field, clinical non-response to this therapy is observed in between 20% and 40% of patients, mostly due to the inability to reach the appropriate pacing site because of anatomical difficulties/absence of veins in the target area.
Recently, conduction system pacing (CSP) has rapidly emerged as an alternative pacing modality to both right ventricular pacing (RVP) and CRT, in order to achieve a more physiological pacing. His bundle pacing (HBP) is considered the physiological pacing "par excellence", but the results in literature show rather frequent technical difficulties due to high pacing thresholds, inadequate ventricular signal amplitude for the detection of intrinsic cardiac activity, low success rate and risk of progression of conduction system pathology in patients with infranodal conduction defects.
Left bundle area pacing has more recently emerged as a viable alternative to achieve physiological pacing with haemodynamic parameters similar to those of HBP, but with lower and stable pacing thresholds, ventricular signal amplitude adequate for the detection of intrinsic cardiac activity and high success rate.
Several experiences with different pacing systems have been published, mainly single-centre studies with small sample sizes and different definitions of conduction system pacing success.
In non-randomised comparative studies, and thus with methodological limitations, clinical superiority over conventional right ventricular pacing, and a substantial efficacy equivalent to CRT in patients with left bundle-branch block, has been shown, creating the preconditions for widespread use of the CSP.
Considering, therefore, the widespread use of the latter technique and the high rate of implants that can potentially benefit from physiological pacing, evaluating safety, feasibility, timing and benefits becomes more crucial than ever.
Therefore, the goal of this observational study is to evaluate the clinical characteristics of patients undergoing permanent cardiac pacing and to compare procedural efficacy and safety of different implantation approaches in the clinical practice of the participating centres.
The contribution of non-fluoroscopic anatomical and electrophysiological reconstruction systems to device implantation procedures will also be evaluated.
The investigators will collect clinical and procedural data from patients with an indication for permanent cardiac pacing who have consecutively undergone an implantable electronic device implant procedure at the Electrophysiology Laboratories of the participating centres over a period of 120 months from the time of approval with a follow-up of an equal 120 months.
Patients will be classified according to the type of stimulation:
- Right chambers endocardial pacing;
- Cardiac resynchronisation therapy;
- Conduction system pacing:
- His bundle pacing
- Left bundle branch area pacing. In addition, the efficacy and safety at 30 days, and the efficacy and safety at 6 and 12 months of the various pacing modalities, will be evaluated.
The investigators defined efficacy at 30 days the presence of stable electrical parameters - or, if unstable, not requiring early re-intervention, the absence of cardiovascular hospitalizations and the absence of cardiovascular death.
The investigators defined safety at 30 days the absence of procedural complications, such as haematoma requiring re-intervention or with haemoglobin loss >2gr/dl, pneumothorax, pericardial effusion requiring drainage, lead dislocation, cardiac implantable electronic device (CIED) infection or a re-intervention for any cause.
Equally, the investigators defined efficacy at 6-12 months the presence of stable electrical parameters - or, if unstable, not requiring re-intervention, the absence of cardiovascular hospitalizations, the absence of cardiovascular death, the occurrence of heart failure, the occurrence or worsening of atrial or ventricular tachyarrhythmias.
Therefore, the investigators defined safety at 6-12 months the proper functioning of the device, the absence of infection and the absence of re-intervention for any cause.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Conventional right ventricular (RV) pacing | – | Device: Cardiac pacing - Conventional RV pacingThe device (pace maker or implantable cardiac defibrillator) is implanted in the subcutaneous subclavian area (right or left) and it is connected to transvenous lead/leads (active or passive) implanted in the right cardiac chambers (atrium and ventricle or ventricle only), which detect intrinsic electrical activity and stimulate when needed. The ventricle pacing might be obtained with an apical or septal stimulation. Vascular access might be from the cephalic, axillary or subclavian veins. Once positioned, lead's pacing threshold, sensing and impedance are measured. If the investigators find good and stable electrical parameters, the catheter(s) is(are) fixed and left in place. |
| Conduction System Pacing | – | Device: Cardiac pacing - Conduction System PacingThe approach for the insertion of the device and of the transvenous leads is similar to the previous ones. The ventricle activation might be obtained with the his bundle stimulation or with the left bundle branch area pacing downstream of the conduction block. Vascular access might be from the cephalic, axillary or subclavian veins. Both selective and non-selective stimulation of the His bundle and the stimulation of the left bundle branch and left septum are considered successful. In both cases, attempts are made to locate the atrio-ventricular junction by fluoroscopic methods or with three-dimensional electroanatomical mapping system. The Hisian potential is sought and the catheter is positioned. In the LBBAP the investigators place the lead 1.5 cm below the His region and, with the pacemaking method, the investigators identify an area that electrocardiographically shows a W signal in V1 lead with D2 more positive than D3 - after checking the electrical parameters. |
| Cardiac resynchronization therapy (CRT) either -pacing (CRTP) or -defibrillation (CRTD) | – | Device: Cardiac pacing - Cardiac resynchronization therapy (pacing - CRTP - or defibrillation - CRTD)The approach for the insertion of the device and of the transvenous leads is similar to the previous ones. The right ventricle pacing (with a pacing lead or a defibrillation coil) might be obtained with an apical or septal stimulation, while the left ventricular pacing is achieved by placing a catheter (active or passive) in the posterolateral area through a venous branch of the coronary sinus. Cardiac resynchronisation therapy (CRT) delivers biventricular or left ventricular only pacing. Vascular access might be from the cephalic, axillary or subclavian veins. Once positioned, lead's pacing threshold, sensing and impedance are measured. If the investigators find good and stable electrical parameters, the catheter(s) is(are) fixed and left in place - paying attention to the phrenic nerve capture threshold. |
| Epicardial pacing | – | Device: Cardiac pacing - Epicardial pacingThe device is usually placed in the subcutaneous abdominal area and the lead(s) is(are) secured in the epicardial surface. It is often used in congenital heart defects or post-cardiac surgery scenarios. Surgeons may access the epicardium during open-heart surgery or with minimally invasive techniques. |
| Leadless pacing | – | Device: Cardiac pacing - Leadless pacingThe leadless device is placed via a percutaneous approach through a large-calibre (femoral) vein inside the right ventricle. It is suitable for patients needing a single chamber pacing such as patients with permanent atrial fibrillation with slow ventricular response, in some cases of paroxysmal atrioventricular block, or patients with a history of CIED infections. The only one currently available has a cardiac muscle fixation system consisting of 4 self-expanding barbs. Once positioned, pacing threshold, sensing and impedance are measured. If the investigators find good and stable electrical parameters, the catheter is left in place. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with an indication for permanent cardiac stimulation who have subsequently undergone an implantation procedure for an implantable electronic device at the Electrophysiology Laboratories of participating centers within a period of 120 months from the time of approval, with a corresponding follow-up period of another 120 months.
Key inclusion criteria (2 listed)
- Indication for cardiac stimulation
- Having performed the implantation of a device for cardiac stimulation
Key exclusion criteria (2 listed)
- Age < 18 years;
- Pregnancy status;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cardiac pacing - Conventional RV pacingAlso: Cardiac defibrillation - Conventional RV pacingImplantation of devices for cardiac pacing/defibrillation | Device | Conventional right ventricular (RV) pacing |
| Cardiac pacing - Conduction System PacingAlso: Cardiac defibrillation - Conduction System PacingImplantation of devices for cardiac pacing/defibrillation | Device | Conduction System Pacing |
| Cardiac pacing - Cardiac resynchronization therapy (pacing - CRTP - or defibrillation - CRTD)Also: Cardiac defibrillation - Cardiac resynchronization therapy (pacing - CRTP - or defibrillation - CRTD)Implantation of devices for cardiac pacing/defibrillation | Device | Cardiac resynchronization therapy (CRT) either -pacing (CRTP) or -defibrillation (CRTD) |
| Cardiac pacing - Epicardial pacingAlso: Cardiac defibrillation - Epicardial pacingImplantation of devices for cardiac pacing/defibrillation | Device | Epicardial pacing |
| Cardiac pacing - Leadless pacingAlso: Cardiac defibrillation - Leadless pacingImplantation of devices for cardiac pacing/defibrillation | Device | Leadless pacing |
Primary outcome
30 days efficacy
Time frame: 30 days
Number of successful implantations, defined as the achievement of the planned pacing modality
Rate of hospitalizations for heart failure at 12 months
Time frame: 12 months
The investigators considered the worsening of heart failure requiring hospital management
All cause death at 12 months
Time frame: 12 months
The investigators will monitor patient's all causes death
17 secondary outcomes
All cause and cardiovascular death at 1, 3, 5, 10 years
Time frame: 120 months
Onset/worsening of heart failure
Time frame: 120 months
Onset/worsening of atrial tachyarrhythmias
Time frame: 120 months
Onset/worsening of ventricular tachyarrhythmias
Time frame: 120 months
Procedural time
Time frame: implantation procedure
Fluoroscopy time
Time frame: implantation procedure
Radiation exposure
Time frame: implantation procedure
Success rate of CRT in heart failure
Time frame: 120 months
Cardiac perforation rate
Time frame: 30 days
Hemothorax rate
Time frame: 30 days
Pneumothorax rate
Time frame: 30 days
Pocket hematoma rate
Time frame: 30 days
Pericardial effusion rate
Time frame: 30 days
Lead dislocation rate
Time frame: 120 months
Lead fracture rate
Time frame: 120 months
Cardiac Implantable Electronic Devices infections rate
Time frame: 120 months
Reintervention rate
Time frame: 120 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2024.
- Derived from this study: PubMed 40880214Bertini M, Canovi L, Vitali F, Marcantoni L, Pastore G, Volpicelli M, Munciguerra O, Biffi M, Ziacchi M, Rossi L, Carinci V, Sirugo P, Pastori P, Imberti JF, Pellegrino PL, Guerriero E, Sassone B, Bertagnin E, Coppola G, Malagu M, Balla C, Azzolini G, Zuccari G, Zanon F, Boriani G, Zuin M. Two-year outcomes of left bundle branch area pacing versus traditional right ventricular pacing in middle-aged adults: a registry-based trial. Europace. 2025 Aug 4;27(8):euaf181. doi: 10.1093/europace/euaf181.
- Derived from this study: PubMed 40439650Bertini M, Vitali F, Malagu M, Azzolini G, Clo S, Canovi L, Farina J, Bianchi N, De Raffele M, Bianchi C, De Pietri M, Guidi Colombi G, Micillo M, Melpignano A, Pavasini R, Balla C, Guardigli G, Vijayaraman P, Zuin M. Left Ventricular Mechanical Insights Into Left Bundle Branch Pacing and Left Ventricular Septal Pacing. JACC Clin Electrophysiol. 2025 Aug;11(8):1852-1861. doi: 10.1016/j.jacep.2025.03.037. Epub 2025 May 28.
Related trials for Arrhythmias, Cardiac
RecruitingObservational study
AI-powered ECG Analysis Using Willem™ Software in High-risk Cardiac Patients (WILLEM)
Cardiomyopathies, Cardiac Arrest
Not yet recruiting
nCPAP-NAVA-Backup Versus Standard nCPAP for Severe Apnea in Preterm Infants ≤28 Weeks
Apnea of Prematurity
Active, not recruiting
Horizon 360 Protocol for the Treatment of Paroxysmal Atrial Fibrillation With the Sphere-360™ Catheter and Affera™ Mapping and Ablation System (Horizon 360)
Paroxysmal AF
Not yet recruiting
Smartphone Camera Measurement of Breathing-Related Heart Rate Variability Compared With ECG in Healthy Adults
Respiratory Sinus Arrhythmia, Heart Rate Variability
Active, not recruitingObservational study
Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Matteo Bertini, MD, PhD principal investigator
Azienda Ospedaliero Universitaria di Ferrara
31 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Arrhythmias, Cardiac and Atrioventricular Block, run by University Hospital of Ferrara at 31 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Matteo Bertini, MD, PhD (+390532236269, brtmtt2@unife.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
30 days efficacy (time frame: 30 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06324682, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2024.