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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Maastricht University Medical Center
Sponsor:
Collaborator:
Medtronic Bakken Research Center
Information provided by (Responsible Party):
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT01609738
First received: April 5, 2012
Last updated: January 7, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Left Ventricular Dysfunction
Cardiac Conduction Defect
Heart Failure
Sick Sinus Syndrome
Device: Left ventricular septum pacing lead
Phase 1
Phase 2

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Left Ventricular Septum Pacing in Patients by Transvenous Approach Through the Inter-ventricular Septum - Feasibility, Long-term Lead Stability and Safety

Resource links provided by NLM:


Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • Number of successful LV septum lead implantations [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    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.

  • Change in sensing values, pacing threshold and lead impedance [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    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.

  • Number of participants with procedure or lead related adverse events [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Acute change in LVdP/dtmax [ Time Frame: Acute measurements are performed for the duration of the lead implantation procedure, an expected average of two hours ] [ Designated as safety issue: No ]

    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 change in LV stroke volume [ Time Frame: Acute measurements are performed for the duration of the lead implantation procedure, an expected average of two hours ] [ Designated as safety issue: No ]

    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 change in QRS duration [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]

    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.

  • Acute change in 3-dimensional QRS vector direction [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]

    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.

  • Acute change in SPECKLE-tracking strain [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]

    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.

  • Difference between relative changes in LV stroke volume assessed by Nexfin and relative changes in invasively measured LVdp/dtmax. [ Time Frame: Acute measurements are performed for the duration of the lead implantation procedure, an expected average of two hours ] [ Designated as safety issue: No ]

    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.


Estimated Enrollment: 12
Study Start Date: November 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Sinus node dysfunction
Patients with sinus node dysfunction and structurally normal hearts
Device: Left ventricular septum pacing lead
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.
Other Name: Adapted Medtronic Select Secure 3830 pacing lead
CRT indication
Patients with an indication for CRT (heart failure with an LVEF <35% and LBBB)
Device: Left ventricular septum pacing lead
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.
Other Name: Adapted Medtronic Select Secure 3830 pacing lead

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Study subjects are recruited from patients referred to the out-patient pacemaker/ICD clinic of our hospital.

Criteria

Inclusion Criteria:

  1. 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
  2. Greater than 18 years of age
  3. Stable sinus rhythm at the time of inclusion
  4. Willing and capable of giving informed consent

Exclusion Criteria:

  1. Ventricular pacing dependent
  2. High degree AV block
  3. Previous septal myocardial infarction
  4. Previously implanted pacing device
  5. Abnormal venous anatomy
  6. Left ventricular septum wall thickness >10mm determined by echocardiography
  7. Presence of severe valvular disease
  8. Presence of an ongoing progressive terminal disease associated with a reduced likelihood of survival for the duration of the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01609738

Contacts
Contact: Masih Mafi Rad, MD +31-43-3871613 masih.mafirad@mumc.nl
Contact: Kevin Vernooy, MD, PhD +31-43-3877095 kevin.vernooy@mumc.nl

Locations
Netherlands
Maastricht University Medical Centre Recruiting
Maastricht, Limburg, Netherlands, 6202 AZ
Contact: Masih Mafi Rad, MD    +31-43-3871613    masih.mafirad@mumc.nl   
Contact: Kevin Vernooy, MD, PhD    +31-43-3877095    kevin.vernooy@mumc.nl   
Sub-Investigator: Masih Mafi Rad, MD         
Sponsors and Collaborators
Maastricht University Medical Center
Medtronic Bakken Research Center
Investigators
Principal Investigator: Frits Prinzen, PhD Maastricht University
Study Director: Kevin Vernooy, MD, PhD Maastricht University Medical Centre
  More Information

Publications:

Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT01609738     History of Changes
Other Study ID Numbers: NL37648.068.11, METC 11-1-047
Study First Received: April 5, 2012
Last Updated: January 7, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht University Medical Center:
Cardiac pacing
Left ventricular septal pacing
Feasibility and safety
Lead stability
Hemodynamics
Left ventricular dyssynchrony
Pacing for heart failure
Cardiac resynchronization therapy

Additional relevant MeSH terms:
Heart Failure
Sick Sinus Syndrome
Ventricular Dysfunction, Left
Ventricular Dysfunction
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Arrhythmia, Sinus
Heart Block
Pathologic Processes

ClinicalTrials.gov processed this record on August 26, 2014