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

Atrial Fibrillation Clinical Trial

— TREEBEARD  

Official title:

Evaluation of conTempoRary Cardiac Stimulation in Clinical practicE: lEft, BivEntriculAr, Right, and conDuction System Pacing

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06324682
• Other study ID #: 825/2022/Oss/AOUFe
• Status: Recruiting
• Start date: January 1, 2023
• Est. completion date: December 31, 2034

Study information

• Verified date: March 2024
• Source: University Hospital of Ferrara
• Contact: Matteo Bertini, MD, PhD
• Phone: +390532236269
• Email: brtmtt2[@]unife.it
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 8400
• Est. completion date: December 31, 2034
• Est. primary completion date: December 31, 2033
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Indication for cardiac stimulation

• Having performed the implantation of a device for cardiac stimulation

Exclusion Criteria:

• Age < 18 years;

• Pregnancy status;

Related Conditions & MeSH terms

• Arrhythmias, Cardiac
• Atrial Fibrillation
• Atrioventricular Block
• Bradyarrhythmia
• Bradycardia
• Bundle-Branch Block
• Heart Arrhythmia
• Heart Block
• Heart Failure
• Heart Failure, Systolic
• Heart Failure,Congestive
• Left Bundle-Branch Block
• Systolic Murmurs
• Tachycardia
• Tachycardia, Ventricular
• Ventricular Arrythmia
• Ventricular Dysfunction
• Ventricular Fibrillation
• Ventricular Tachycardia

Intervention

Device:
• Cardiac pacing - Conventional RV pacing
Implantation of devices for cardiac pacing/defibrillation
• Cardiac pacing - Conduction System Pacing
Implantation of devices for cardiac pacing/defibrillation
• Cardiac pacing - Cardiac resynchronization therapy (pacing - CRTP - or defibrillation - CRTD)
Implantation of devices for cardiac pacing/defibrillation
• Cardiac pacing - Epicardial pacing
Implantation of devices for cardiac pacing/defibrillation
• Cardiac pacing - Leadless pacing
Implantation of devices for cardiac pacing/defibrillation

Locations

Country	Name	City	State
Italy	Ospedale San Donato	Arezzo
Italy	Azienda Ospedaliero-Universitaria S.Orsola-Malpighi Bologna	Bologna
Italy	spedale Maggiore di Bologna	Bologna
Italy	Ospedale Bernardino Ramazzini	Carpi
Italy	Ospedale SS Annunziata	Cento
Italy	Ospedale Bufalini	Cesena
Italy	Ospedale San Giuseppe	Empoli
Italy	Azienda Ospedaliero-Universitaria di Ferrara	Ferrara	FE
Italy	Ospedale di Vaio	Fidenza
Italy	Azienda Ospedaliero-Universitaria Careggi	Firenze
Italy	Ospedale San Giovanni di Dio	Firenze
Italy	Ospedale Santa Maria Annunziata Bagno a Ripoli	Firenze
Italy	Azienda Ospedaliero-Universitaria "Ospedali Riuniti"	Foggia
Italy	Ospedale Morgagni-Pierantoni	Forlì
Italy	Ospedale Santa Maria della Misericordia Grosseto	Grosseto
Italy	Ospedale della Versilia	Lido Di Camaiore
Italy	Ospedali Riuniti di Livorno	Livorno
Italy	Ospedale San Luca	Lucca
Italy	Nuovo ospedale Apuano Massa	Massa
Italy	Azienda Ospedaliero-Universitaria Policlinico di Modena	Modena
Italy	Ospedale Sant'Agostino Estense Modena Baggiovara	Modena
Italy	Ospedale Civico, azienda Ospedaliera di Palermo	Palermo
Italy	Policlinico Paolo Giaccone	Palermo
Italy	Azienda Ospedaliero-Universitaria Maggiore	Parma
Italy	Ospedale Guglielmo da Saliceto Piacenza	Piacenza
Italy	Azienda Ospedaliero-Universitaria pisana Cisanello	Pisa
Italy	Fondazione Toscana Gabriele Monasterio	Pisa
Italy	Ospedale Santa Maria delle Croci	Ravenna
Italy	ASMN Reggio Emilia	Reggio Emilia
Italy	Ospedale degli Infermi Rimini	Rimini
Italy	Azienda Ospedaliero-Universitaria Senese	Siena

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital of Ferrara

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	30 days efficacy	Number of successful implantations, defined as the achievement of the planned pacing modality	30 days
Primary	Rate of hospitalizations for heart failure at 12 months	The investigators considered the worsening of heart failure requiring hospital management	12 months
Primary	All cause death at 12 months	The investigators will monitor patient's all causes death	12 months
Secondary	All cause and cardiovascular death at 1, 3, 5, 10 years	The investigators will monitor patient's all causes and cardiovascular death	120 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Procedural time	The investigators will evaluate procedural time of different cardiac pacing modalities	implantation procedure
Secondary	Fluoroscopy time	The investigators will evaluate fluoroscopy time of different cardiac pacing modalities	implantation procedure
Secondary	Radiation exposure	The investigators will evaluate radiation exposure of different cardiac pacing modalities monitoring the dose area product	implantation procedure
Secondary	Success rate of CRT in heart failure	The investigators consider successful CRT if obtain a left ventricular end-systolic volume reduction >15%	120 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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