ConTempoRary Cardiac Stimulation in Clinical practicE: lEft, BivEntriculAr, Right, and conDuction System Pacing (TREEBEARD)

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.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation; Arrhythmias, Cardiac; Left Bundle-Branch Block; Bundle-Branch Block; Ventricular Fibrillation; Ventricular Tachycardia; Ventricular Dysfunction; Atrioventricular Block; Heart Failure, Systolic; Ventricular Arrythmia; Heart Failure，Congestive; Bradyarrhythmia; Heart Arrhythmia; Reduced Systolic Function; Atrioventricular Nodal Disease; Atrioventricular Conduction Defects; Atrioventricular Block Complete; Atrioventricular Block Incomplete; Atrioventricular Junctional Rhythm; Block;Atrioventricular; Block; Arrhythmic; Block; Mobitz; Block, Heart; Block, Fascicular; Block Branch Bundle Left
• Intervention / Treatment: Device: Cardiac pacing - Conventional RV pacing; Device: Cardiac pacing - Conduction System Pacing; Device: Cardiac pacing - Cardiac resynchronization therapy (pacing - CRTP - or defibrillation - CRTD); Device: Cardiac pacing - Epicardial pacing; Device: Cardiac pacing - Leadless pacing

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:

1. Right chambers endocardial pacing;
2. Cardiac resynchronisation therapy;

3. Conduction system pacing:

   1. His bundle pacing
   2. 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 Type: Observational
• Enrollment (Estimated): 8400

Contacts and Locations

• Study Contact: Name: Matteo Bertini, MD, PhD; Phone Number: +390532236269; Email: brtmtt2@unife.it

Study Locations

• Italy
  • Arezzo, Italy
    • Recruiting
    • Ospedale San Donato
    • Contact: Pasquale Notarstefano, MD
  • Bologna, Italy, 40138
    • Recruiting
    • Azienda Ospedaliero-Universitaria S.Orsola-Malpighi Bologna
    • Contact: Mauro Biffi, MD
  • Bologna, Italy
    • Recruiting
    • spedale Maggiore di Bologna
    • Contact: Valeria Carinci, MD
  • Carpi, Italy
    • Recruiting
    • Ospedale Bernardino Ramazzini
    • Contact: Elia De Maria, MD
  • Cento, Italy
    • Recruiting
    • Ospedale SS Annunziata
    • Contact: Biagio Sassone, MD
  • Cesena, Italy
    • Recruiting
    • Ospedale Bufalini
    • Contact: Paolo Sabbatani, MD
  • Empoli, Italy
    • Recruiting
    • Ospedale San Giuseppe
    • Contact: Attilio Del Rosso, MD
  • Fidenza, Italy
    • Recruiting
    • Ospedale di Vaio
    • Contact: Paolo Pastori
  • Firenze, Italy
    • Recruiting
    • Azienda Ospedaliero-Universitaria Careggi
    • Contact: Giuseppe Ricciardi, MD
  • Firenze, Italy
    • Recruiting
    • Ospedale San Giovanni di Dio
    • Contact: Iacopo Bertolozzi, MD
  • Firenze, Italy
    • Recruiting
    • Ospedale Santa Maria Annunziata Bagno a Ripoli
    • Contact: Maria Giaccardi, MD
  • Foggia, Italy
    • Recruiting
    • Azienda Ospedaliero-Universitaria "Ospedali Riuniti"
    • Contact: Pier Luigi Pellegrino, MD
  • Forlì, Italy
    • Recruiting
    • Ospedale Morgagni-Pierantoni
    • Contact: Alberto Bandini, MD
  • Grosseto, Italy
    • Recruiting
    • Ospedale Santa Maria della Misericordia Grosseto
    • Contact: Gennaro Miracapillo, MD
  • Lido Di Camaiore, Italy
    • Recruiting
    • Ospedale della Versilia
    • Contact: Gianluca Solarino, MD
  • Livorno, Italy
    • Recruiting
    • Ospedali Riuniti di Livorno
    • Contact: Federica Lapira, MD
  • Lucca, Italy
    • Recruiting
    • Ospedale San Luca
    • Contact: Davide Giorgi, MD
  • Massa, Italy
    • Recruiting
    • Nuovo ospedale Apuano Massa
    • Contact: Giuseppe Arena, MD
  • Modena, Italy
    • Recruiting
    • Azienda Ospedaliero-Universitaria Policlinico di Modena
    • Contact: Giuseppe Boriani, PhD
  • Modena, Italy
    • Recruiting
    • Ospedale Sant'Agostino Estense Modena Baggiovara
    • Contact: Mauro Zennaro, MD
  • Palermo, Italy
    • Recruiting
    • Policlinico Paolo Giaccone
    • Contact: Giuseppe Coppola, MD
  • Palermo, Italy
    • Recruiting
    • Ospedale Civico, azienda Ospedaliera di Palermo
    • Contact: Giuseppe Sgarito, MD
  • Parma, Italy
    • Recruiting
    • Azienda Ospedaliero-Universitaria Maggiore
    • Contact: Francesca Maria Notarangelo, MD
  • Piacenza, Italy, 29100
    • Recruiting
    • Ospedale Guglielmo da Saliceto Piacenza
    • Contact: Luca Rossi, MD
  • Pisa, Italy
    • Recruiting
    • Fondazione Toscana Gabriele Monasterio
    • Contact: Andrea Rossi, MD
  • Pisa, Italy
    • Recruiting
    • Azienda Ospedaliero-Universitaria pisana Cisanello
    • Contact: Giulio Zucchelli
  • Ravenna, Italy
    • Recruiting
    • Ospedale Santa Maria delle Croci
    • Contact: Alessandro Dal Monte
  • Reggio Emilia, Italy
    • Recruiting
    • ASMN Reggio Emilia
    • Contact: Fabio Quartieri, MD
  • Rimini, Italy
    • Recruiting
    • Ospedale degli Infermi Rimini
    • Contact: Davide Saporito, MD
  • Siena, Italy
    • Recruiting
    • Azienda Ospedaliero-Universitaria Senese
    • Contact: Amato Santoro, MD
  • FE
    • Ferrara, FE, Italy, 44124
      • Recruiting
      • Azienda Ospedaliero-Universitaria di Ferrara
      • Contact: Matteo Bertini, MD, PhD; Phone Number: +390532236269; Email: brtmtt2@unife.it

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

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.

Description

Inclusion Criteria:

• Indication for cardiac stimulation
• Having performed the implantation of a device for cardiac stimulation

Exclusion Criteria:

• Age < 18 years;
• Pregnancy status;

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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.	Device: Cardiac pacing - Conventional RV pacing; Implantation of devices for cardiac pacing/defibrillation; Other Names: Cardiac defibrillation - 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.	Device: Cardiac pacing - Conduction System Pacing; Implantation of devices for cardiac pacing/defibrillation; Other Names: Cardiac defibrillation - 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.	Device: Cardiac pacing - Cardiac resynchronization therapy (pacing - CRTP - or defibrillation - CRTD); Implantation of devices for cardiac pacing/defibrillation; Other Names: Cardiac defibrillation - 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.	Device: Cardiac pacing - Epicardial pacing; Implantation of devices for cardiac pacing/defibrillation; Other Names: Cardiac defibrillation - 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.	Device: Cardiac pacing - Leadless pacing; Implantation of devices for cardiac pacing/defibrillation; Other Names: Cardiac defibrillation - Leadless pacing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30 days efficacy	Number of successful implantations, defined as the achievement of the planned pacing modality	30 days
Rate of hospitalizations for heart failure at 12 months	The investigators considered the worsening of heart failure requiring hospital management	12 months
All cause death at 12 months	The investigators will monitor patient's all causes death	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause and cardiovascular death at 1, 3, 5, 10 years	The investigators will monitor patient's all causes and cardiovascular death	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	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.	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.	120 months
Procedural time	The investigators will evaluate procedural time of different cardiac pacing modalities	implantation procedure
Fluoroscopy time	The investigators will evaluate fluoroscopy time of different cardiac pacing modalities	implantation procedure
Radiation exposure	The investigators will evaluate radiation exposure of different cardiac pacing modalities monitoring the dose area product	implantation procedure
Success rate of CRT in heart failure	The investigators consider successful CRT if obtain a left ventricular end-systolic volume reduction >15%	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	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	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	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	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	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	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	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	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	120 months

Collaborators and Investigators

• Sponsor: University Hospital of Ferrara
• Investigators: Principal Investigator: Matteo Bertini, MD, PhD, Azienda Ospedaliero Universitaria di Ferrara

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): December 31, 2033
• Study Completion (Estimated): December 31, 2034

Study Registration Dates

• First Submitted: January 31, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Heart failure; Secondary prevention; Primary prevention; Implantable cardioverter defibrillator (ICD); CRT; Ventricular Tachycardia; Ventricular Dysfunction; Ventricular Fibrillation; Cardiac Resynchronization therapy; Ventricular Arrythmia; Atrioventricular Block; Left bundle branch area pacing (LBBAP); CSP; Bradyarrhythmia; Pace maker (PM); Conduction System Pacing; His Pacing; Atrioventricular Block Complete
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Heart Murmurs; Heart Failure; Atrial Fibrillation; Bundle-Branch Block; Heart Block; Bradycardia; Arrhythmias, Cardiac; Ventricular Fibrillation; Tachycardia; Tachycardia, Ventricular; Systolic Murmurs; Cardiac Conduction System Disease; Heart Failure, Systolic; Ventricular Dysfunction; Atrioventricular Block
• Other Study ID Numbers: 825/2022/Oss/AOUFe

Drug and device information, study documents

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