RV Septal Versus Minimized RV Pacing in Sick Sinus Syndrome (VOTE)

Klinikum Nürnberg

Status: Unknown

Conditions: Sick Sinus Syndrome

Treatments: Procedure: pacemaker implantation, AAI(R)-DDD(R) versus DDD(R)

Study type: Observational

Funder types: Other

Identifiers

NCT01477138

VOTEPM

Details and patient eligibility

About

Background:

• Potential negative effects of pacing in the RV-apex are well documented
• However, study results comparing septal / RVOT-pacing versus RV-apical pacing controversial.
• The optimal pacing mode in SSS (DDDR versus AAIR) is unclear, as the DDD (R) mode with an AV delay ≤ 220 ms should be the preferred pacing mode, according to the DANPACE trial [DANPACE, ESC 2010, Stockholm].

Aim:

• to evaluate chronic effects of proven right ventricular septal compared to minimized right ventricular septal pacing in patients with SSS

Inclusion criterion:

-Pacemaker indication according to current guidelines: sick sinus syndrome (SSS)

Exclusion criteria:

• Life expectancy < 2 years
• Age <18 years
• Noncompliance with regard to participation in the study
• Pregnancy
• AV block ° 2 and higher
• Permanent atrial fibrillation
• Heart failure NYHA III and IV, reduced LV-EF <40%
• ICD indication
• Acute coronary syndrome. PCI or CABG <3 months
• Heart transplant
• Placement of septal RV electrode is not possible

Study design:

• Prospective, monocentric, randomized, double-blinded
• Run-in phase: for weeks AAI [R]-DDD [R]
• Randomization: two groups A) septal right ventricular chamber pacing: mode DDD [R] versus B) Reduction of unnecessary ventricular pacing: AAI [R]-DDD [R].
• FU: 6 and 12-months

Primary endpoints:

-LV ejection fraction and end-systolic LV volume after 12 months.

Secondary endpoints:

-LV end-diastolic volume, TAPSE, parameters of dyssynchrony (SPWMD, LV-PEP, IVMD), AF-burden, % ventricular pacing, CPX: peak oxygen consumption (peak VO2), VO2 AT, VO2/HR, VE/VCO2 slope; QoL scores (SF-36) after 12 months.

Statistics/sample size estimation:

In order to detect a difference in LVEF of 5% and for LV-ESV of 5 mL between the 2 groups after 12 months:

• 90% power/alpha 5%: 84 patients per group

• 80% power/alpha 5%: 63 patients per group

  • 10% for compensation of drop-outs / patients lost of follow-up. Two-sided 5% type 1 error Analysis intention-to-treat and based on the finally programmed pacing mode.

Material

• PG: market released dual chamber pacemakers with the ability to pace AAI(R) -DDD(R)
• pacing leads: market-released standard active electrodes
• RV electrode: septal verified under multi-level screening (RAO/LAO) and ECG (LBBB narrow <150 ms / inferior axis)

Full description

Background:

• Potential negative effects of pacing in the RV-apex are well documented
• Asynchronous ventricular activation
• reduction of systolic and diastolic LV function
• Experimental data: histological changes
• Asymmetric LV hypertrophy and thinning
• However, study results comparing septal / RVOT-pacing versus RV-apical pacing controversial:
• Acute versus chronic
• Small number of cases, uncontrolled, unblinded,
• Brief periods of observation in the cross-over design (3 months)
• "RVOT" often summarizes different stimulation sites: high RVOT, lateral, septal. Actually only limited data with proven septal stimulation
• No objective performance assessment (CPX)
• Assessment of alternative stimulation site previously RVOT versus RV-apex,
• ventricular pacing compared to ventricular pacing, then tested a potential harm to another
• The question of the optimal pacing mode of patients with SSS (DDDR versus AAIR) appears to be open again. While in Germany, two-chamber systems with AAI [R] mode with ventricular back-up are used, should the DDD (R) mode with an AV delay ≤ 220 ms be the preferred pacing mode, according to the results of the DANPACE trial for patients with SSS [DANPACE, ESC 2010, Stockholm].

Aim:

• to evaluate chronic effects of proven right ventricular septal compared to minimized right ventricular septal pacing in patients with SSS

Inclusion criterion:

-Pacemaker indication according to current guidelines: sick sinus syndrome (SSS)

Exclusion criteria:

• Life expectancy < 2 years
• Age <18 years
• Noncompliance with regard to participation in the study
• Pregnancy
• AV block ° 2 and higher
• Permanent atrial fibrillation
• Heart failure NYHA III and IV, reduced LV-EF <40%
• ICD indication
• Acute coronary syndrome. PCI or CABG <3 months
• Heart transplant
• Placement of septal RV electrode is not possible

Study design:

• Prospective, monocentric, randomized, double-blinded
• Run-in phase: 4 weeks AAI [R]-DDD [R]
• ECG, PM-interrogation, echocardiography, performance diagnostics, CPX, QoL questionnaire
• Randomization: two groups 4 weeks (between 3 to 6 weeks) after implant A) septal right ventricular chamber pacing: mode DDD [R] versus B) Reduction of unnecessary ventricular pacing: AAI [R]-DDD [R].
• FU: 6 and 12-months
• ECG, Holter-ECG, PM-interrogation, echocardiography, performance diagnostics, CPX, QoL questionnaire
• Extension of follow-up if possible

Primary endpoints:

-LV ejection fraction and end-systolic LV volume after 12 months.

Secondary endpoints:

-LV end-diastolic volume, TAPSE, parameters of dyssynchrony (SPWMD, LV-PEP, IVMD), AF-burden, % ventricular pacing, CPX: peak oxygen consumption (peak VO2), VO2 AT, VO2/HR, VE/VCO2 slope; QoL scores (SF-36) after 12 months.

Blinding:

• Patient compared to the pacing mode
• Physician: offline analysis of echo and CPX blinded to the pacing mode

Statistics/sample size estimation:

In order to detect a difference in LVEF of 5% and for LV-ESV of 5 mL between the 2 groups after 12 months:

• 90% power/alpha 5%: 84 patients per group

• 80% power/alpha 5%: 63 patients per group

  • 10% for compensation of drop-outs / patients lost of follow-up. Two-sided 5% type 1 error Analysis intention-to-treat and based on the finally programmed pacing mode.

Material

• PG: market released dual chamber pacemakers with the ability to pace AAI(R) -DDD(R)
• pacing leads: market-released standard active electrodes (eg. BSCI FineLine 4470 and 4471) Implantation
• Transvenously
• RA-electrode: if possible, short atrial conduction time
• RV electrode: septal verified under multi-level screening (RAO/LAO) and ECG (LBBB narrow <150 ms / inferior axis)

Enrollment: 126 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Pacemaker indication according to current guidelines: sick sinus syndrome (SSS)

Exclusion criteria

• Life expectancy <2 years
• Age < 18 years
• Noncompliance with regard to participation in the study
• Pregnancy
• AV block ° 2 and higher
• Permanent atrial fibrillation
• Heart failure NYHA III and IV, reduced LV-EF < 40%
• ICD indication
• Acute coronary syndrome. PCI or CABG < 3 months
• Heart transplant
• Placement of septal RV electrode is not possible

Trial design

126 participants in 2 patient groups

DDD(R)

Description:

SSS. PM programmed to DDD(R) mode with ventricular pacing on the right ventricular septum.

Treatment:

Procedure: pacemaker implantation, AAI(R)-DDD(R) versus DDD(R)

AAI(R)<=>DDD(R)

Description:

SSS, PM-mode programmed for minimizing right ventricular pacing on the right interventricular septum

Treatment:

Procedure: pacemaker implantation, AAI(R)-DDD(R) versus DDD(R)