Left Ventricular Septum Pacing in Patients by Transvenous Approach Through the Inter-ventricular Septum

Study Overview
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Brief Summary
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Cardiac pacing is the only effective treatment for symptomatic bradycardia. The right ventricular apex (RVA) has become the most frequently used ventricular pacing site. However, RVA pacing has been shown to cause left ventricular (LV) dyssynchrony wich can lead to LV dysfunction and development of heart failure. Recent studies in animals have demonstrated that pacing at the LV septum induces significantly less ventricular dyssynchrony than RVA pacing and is able to improve LV function to a similar degree as biventricular (BiV) pacing. In addition it was shown that a LV septum lead can be placed permanently by driving a lead with extended helix from the RV side through the inter-ventricular septum into the LV endocardial layer. This was shown to be a feasible and safe procedure and lead stability was shown during four months of follow-up in otherwise healthy and active canines. LV septum pacing may therefore be a good treatment alternative in patients with symptomatic bradycardia, as well as patients with an indication for cardiac resynchronization therapy (CRT). The purpose of this study is to translate the findings from preclinical studies to the clinical situation by investigating the feasibility, long-term lead stability and safety of LV septum pacing by transvenous approach through the inter-ventricular septum in patients.

Detailed Description
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Cardiac pacing is the only effective treatment for symptomatic bradycardia. After the introduction of the implantable pacemaker (PM), the right ventricular apex (RVA) has become the most frequently used ventricular pacing site. However, clinical studies have shown that RVA pacing leads to left ventricular (LV) dyssynchrony, and on the long run to adverse structural changes (remodeling), a higher risk of developing atrial fibrillation and heart failure, and higher mortality. Recognition of the adverse effects of RVA pacing has generated interest in alternative ventricular pacing sites. Recent studies in animals have shown that pacing at the LV septum induces significantly less ventricular dyssynchrony than RVA pacing. In addition it was shown that a LV septum lead can be placed permanently by introducing a custom lead with extended helix transvenously and, after positioning it against the RV septum, driving it through the inter-ventricular septum into the LV endocardial layer. This was shown to be a feasible and safe procedure and lead stability was shown during four months of follow-up in otherwise healthy and active canines. Animal studies have also shown that LV septum pacing is able to improve LV function to a similar degree as simultaneous biventricular (BiV) pacing used in cardiac resynchronization therapy (CRT). CRT was introduced to restore the abnormal ventricular activation and contraction in patients with heart failure and intra-ventricular conduction delay. Large clinical trials have shown that CRT improves LV systolic pump function, reverses structural remodelling, improves quality of life and exercise tolerance, and decreases mortality. Unfortunately, problems encountered during positioning and fixation of the LV pacing lead in the coronary vein result in suboptimal or loss of CRT in at least a quarter of CRT candidates and require re-operation in 7% during follow up. The adverse effects of RVA pacing, the limitations of BiV pacing and the promising effects of LV septum pacing in preclinical studies have led to the idea that LV septum pacing may be a good treatment alternative in patients with symptomatic bradycardia, as well as patients with an indication for CRT. In the latter category, CRT could then be performed using a single ventricular pacing lead, thus limiting the number of lead implantations, and thereby reducing complication rate and implantation costs as well as avoiding the difficult access route through the coronary vein. It is the aim of this study to translate the findings from preclinical studies to the clinical situation by investigating the feasibility, long-term lead stability and safety of LV septum pacing by transvenous approach through the inter-ventricular septum in patients with a PM or CRT indication. The results may have a large impact on future pacing therapy. The LV septum may become the universal pacing site, being preferred for anti-bradycardia therapy, and being an equal alternative for BiV pacing, but easier to apply, less invasive and more cost-effective.

Official Title
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Left Ventricular Septum Pacing in Patients by Transvenous Approach Through the Inter-ventricular Septum - Feasibility, Long-term Lead Stability and Safety

Conditions
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Left Ventricular Dysfunction, Cardiac Conduction Defect, Heart Failure, Sick Sinus Syndrome

Intervention / Treatment
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* Device: Left ventricular septum pacing lead


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cardiac pacing indication for sinus node dysfunction (dual chamber pacemaker) or indication for CRT (BiV pacemaker). Patient with sinus node dysfunction: Normal left ventricular ejection fraction (LVEF > 50%) Left ventricular end-diastolic diameter (LVEDD) < 55mm QRS duration < 100ms Patient with CRT indication: Non-ischemic cardiomyopathy LVEF is < 35% Typical left bundle-branch block on surface ECG QRS duration >150ms NYHA functional class I-III Greater than 18 years of age Stable sinus rhythm at the time of inclusion Willing and capable of giving informed consent Exclusion Criteria: Ventricular pacing dependent High degree AV block Previous septal myocardial infarction Previously implanted pacing device Abnormal venous anatomy Left ventricular septum wall thickness >10mm determined by echocardiography Presence of severe valvular disease Presence of an ongoing progressive terminal disease associated with a reduced likelihood of survival for the duration of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sinus node dysfunction<br>Patients with sinus node dysfunction and structurally normal hearts | Device: Left ventricular septum pacing lead<br>* A left ventricular septum pacing lead is permanently placed by introducing a custom lead with extended helix transvenously and, after positioning it against the RV septum, driving it through the inter-ventricular septum into the LV endocardial layer.<br>* Other names: Adapted Medtronic Select Secure 3830 pacing lead;|
| CRT indication<br>Patients with an indication for CRT (heart failure with an LVEF <35% and LBBB) | Device: Left ventricular septum pacing lead<br>* A left ventricular septum pacing lead is permanently placed by introducing a custom lead with extended helix transvenously and, after positioning it against the RV septum, driving it through the inter-ventricular septum into the LV endocardial layer.<br>* Other names: Adapted Medtronic Select Secure 3830 pacing lead;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of successful LV septum lead implantations | LV septum lead implantation is considered successful if the lead can be placed in the endocardial LV septum and adequate and stable sensing and pacing tresholds are achieved. | Baseline and 6 months | 
| Change in sensing values, pacing threshold and lead impedance | Maintenance of stable lead function is determined by assessment of change in the electrical parameters: sensing value, pacing threshold and lead impedance at baseline versus 6 months follow-up. | Baseline and 6 months | 
| Number of participants with procedure or lead related adverse events | The number of participant with and the kind of procedure- or lead related complications are assessed at the time of the procedure and up to 6 months after lead implantation. Special attention is given to the presence of perforation or rupture of the inter-ventricular septum or free wall, pericardial effusion, thrombosis, heart rhythm disturbances, conduction disturbances, and lead-/screw dislocation/-fracture. | Baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute change in LVdP/dtmax | Acute change in LV systolic function using the hemodynamic parameter LVdP/dtmax during LV septum pacing compared to: RVA pacing and baseline (atrial pacing / AAI mode) in patients with SND. RVA pacing, single LV epicardial lateral wall pacing, Bi-LV pacing (LV septum and LV lateral wall pacing), BiV pacing (RV septum and LV lateral wall pacing) and baseline (atrial pacing / AAI mode) in heart failure patients who are candidates for CRT. | Acute measurements are performed for the duration of the lead implantation procedure, an expected average of two hours | 
| Acute change in LV stroke volume | Acute change in LV systolic function using the hemodynamic parameter LV stroke volume measured by Nexfin, during LV septum pacing compared to: RVA pacing and baseline (atrial pacing / AAI mode) in patients with SND. RVA pacing, single LV epicardial lateral wall pacing, Bi-LV pacing (LV septum and LV lateral wall pacing), BiV pacing (RV septum and LV lateral wall pacing) and baseline (atrial pacing / AAI mode) in heart failure patients who are candidates for CRT. | Acute measurements are performed for the duration of the lead implantation procedure, an expected average of two hours | 
| Acute change in QRS duration | Acute change in sequence of LV electrical activation using the electrocardiographic parameter QRS duration, during LV septum pacing compared to: RVA pacing and baseline (atrial pacing / AAI mode) in patients with SND. RVA pacing, single LV epicardial lateral wall pacing, Bi-LV pacing (LV septum and LV lateral wall pacing), BiV pacing (RV septum and LV lateral wall pacing) and baseline (atrial pacing / AAI mode) in heart failure patients who are candidates for CRT. | Baseline and 4 weeks | 
| Acute change in 3-dimensional QRS vector direction | Acute change in sequence of LV electrical activation using the electrocardiographic parameter 3-dimensional QRS vector direction, during LV septum pacing compared to: RVA pacing and baseline (atrial pacing / AAI mode) in patients with SND. RVA pacing, single LV epicardial lateral wall pacing, Bi-LV pacing (LV septum and LV lateral wall pacing), BiV pacing (RV septum and LV lateral wall pacing) and baseline (atrial pacing / AAI mode) in heart failure patients who are candidates for CRT. | Baseline and 4 weeks | 
| Acute change in SPECKLE-tracking strain | Acute change in regional myocardial deformation patterns using the echocardiographic parameter SPECKLE-tracking strain, during LV septum pacing compared to: RVA pacing and baseline (atrial pacing / AAI mode) in patients with SND. RVA pacing, single LV epicardial lateral wall pacing, Bi-LV pacing (LV septum and LV lateral wall pacing), BiV pacing (RV septum and LV lateral wall pacing) and baseline (atrial pacing / AAI mode) in heart failure patients who are candidates for CRT. | Baseline and 4 weeks | 
| Difference between relative changes in LV stroke volume assessed by Nexfin and relative changes in invasively measured LVdp/dtmax. | Correlation between the relative change in non-invasively measured LV stroke volume using Nexfin and the relatieve change in invasively determined LV dP/dtmax, during LV septum pacing compared to: RVA pacing and baseline (atrial pacing / AAI mode) in patients with SND. RVA pacing, single LV epicardial lateral wall pacing, Bi-LV pacing (LV septum and LV lateral wall pacing), BiV pacing (RV septum and LV lateral wall pacing) and baseline (atrial pacing / AAI mode) in heart failure patients who are candidates for CRT. | Acute measurements are performed for the duration of the lead implantation procedure, an expected average of two hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac pacing, Left ventricular septal pacing, Feasibility and safety, Lead stability, Hemodynamics, Left ventricular dyssynchrony, Pacing for heart failure, Cardiac resynchronization therapy