Clinical trial NCT06324682: ConTempoRary Cardiac Stimulation in Clinical practicE: lEft, BivEntriculAr, Right, and conDuction System Pacing
Official title: Evaluation of conTempoRary Cardiac Stimulation in Clinical practicE: lEft, BivEntriculAr, Right, and conDuction System Pacing
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Arrhythmias, Cardiac
Atrioventricular Block
Reduced Systolic Function
Atrial Fibrillation
Bradyarrhythmia
Ventricular Tachycardia
Ventricular Dysfunction
Ventricular Fibrillation
Ventricular Arrythmia
Atrioventricular Nodal Disease
Atrioventricular Conduction Defects
Atrioventricular Block Complete
Atrioventricular Block Incomplete
Atrioventricular Junctional Rhythm
Bundle-Branch Block
Left Bundle-Branch Block
Heart Failure, Systolic
Block;Atrioventricular
Block; Arrhythmic
Block; Mobitz
Block, Heart
Block, Fascicular
Block Branch Bundle Left
Heart Failure，Congestive
Heart Arrhythmia
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
Lead sponsor: University Hospital of Ferrara
Sponsor class: OTHER
First posted: 2024-03-22
Enrollment: 8400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* Age \< 18 years;
* Pregnancy status;

Primary outcomes:
measure: 30 days efficacy
timeFrame: 30 days
measure: Rate of hospitalizations for heart failure at 12 months
timeFrame: 12 months
measure: All cause death at 12 months
timeFrame: 12 months
Secondary outcomes:
measure: All cause and cardiovascular death at 1, 3, 5, 10 years
timeFrame: 120 months
measure: Onset/worsening of heart failure
timeFrame: 120 months
measure: Onset/worsening of atrial tachyarrhythmias
timeFrame: 120 months
measure: Onset/worsening of ventricular tachyarrhythmias
timeFrame: 120 months
measure: Procedural time
timeFrame: implantation procedure
measure: Fluoroscopy time
timeFrame: implantation procedure
measure: Radiation exposure
timeFrame: implantation procedure
measure: Success rate of CRT in heart failure
timeFrame: 120 months
measure: Cardiac perforation rate
timeFrame: 30 days
measure: Hemothorax rate
timeFrame: 30 days
measure: Pneumothorax rate
timeFrame: 30 days
measure: Pocket hematoma rate
timeFrame: 30 days
measure: Pericardial effusion rate
timeFrame: 30 days
measure: Lead dislocation rate
timeFrame: 120 months
measure: Lead fracture rate
timeFrame: 120 months
measure: Cardiac Implantable Electronic Devices infections rate
timeFrame: 120 months
measure: Reintervention rate
timeFrame: 120 months
Other outcomes:
Locations:
city: Ferrara
country: Italy
facility: Azienda Ospedaliero-Universitaria di Ferrara
state: FE
city: Arezzo
country: Italy
facility: Ospedale San Donato
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria S.Orsola-Malpighi Bologna
city: Bologna
country: Italy
facility: spedale Maggiore di Bologna
city: Carpi
country: Italy
facility: Ospedale Bernardino Ramazzini
city: Cento
country: Italy
facility: Ospedale SS Annunziata
city: Cesena
country: Italy
facility: Ospedale Bufalini
city: Empoli
country: Italy
facility: Ospedale San Giuseppe
city: Fidenza
country: Italy
facility: Ospedale di Vaio
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
city: Firenze
country: Italy
facility: Ospedale San Giovanni di Dio
city: Firenze
country: Italy
facility: Ospedale Santa Maria Annunziata Bagno a Ripoli
city: Foggia
country: Italy
facility: Azienda Ospedaliero-Universitaria "Ospedali Riuniti"
city: Forlì
country: Italy
facility: Ospedale Morgagni-Pierantoni
city: Grosseto
country: Italy
facility: Ospedale Santa Maria della Misericordia Grosseto
city: Lido Di Camaiore
country: Italy
facility: Ospedale della Versilia
city: Livorno
country: Italy
facility: Ospedali Riuniti di Livorno
city: Lucca
country: Italy
facility: Ospedale San Luca
city: Massa
country: Italy
facility: Nuovo ospedale Apuano Massa
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico di Modena
city: Modena
country: Italy
facility: Ospedale Sant'Agostino Estense Modena Baggiovara
city: Palermo
country: Italy
facility: Ospedale Civico, azienda Ospedaliera di Palermo
city: Palermo
country: Italy
facility: Policlinico Paolo Giaccone
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria Maggiore
city: Piacenza
country: Italy
facility: Ospedale Guglielmo da Saliceto Piacenza
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria pisana Cisanello
city: Pisa
country: Italy
facility: Fondazione Toscana Gabriele Monasterio
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
city: Reggio Emilia
country: Italy
facility: ASMN Reggio Emilia
city: Rimini
country: Italy
facility: Ospedale degli Infermi Rimini
city: Siena
country: Italy
facility: Azienda Ospedaliero-Universitaria Senese
Study officials:
affiliation: Azienda Ospedaliero Universitaria di Ferrara
name: Matteo Bertini, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: