RV Septal Versus Minimized RV Pacing in Sick Sinus Syndrome — VOTE  

Sick Sinus Syndrome Clinical Trial

Official title: Comparison of Right Ventricular Septal Pacing to Minimized Right Ventricular Septal Stimulation in Patients With Sick Sinus Syndrome

Status Recruiting

Clinical Trial Summary

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)

Clinical Trial 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) ;

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Sick Sinus Syndrome
• Syndrome

• NCT number: NCT01477138
• Study type: Observational
• Source: Klinikum Nürnberg
• Contact: Dirk Bastian, Dr.med
• Phone: +499113982989
• Email: dirk.bastian@klinikum-nuernberg.de
• Status: Recruiting
• Phase: N/A
• Start date: July 2011
• Completion date: December 2013