RV Septal Versus Minimized RV Pacing in Sick Sinus Syndrome

Study Overview
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Brief Summary
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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)

Detailed Description
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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)

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

Conditions
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Sick Sinus Syndrome

Intervention / Treatment
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* Procedure: pacemaker implantation, AAI(R)-DDD(R) versus DDD(R)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| DDD(R)<br>SSS. PM programmed to DDD(R) mode with ventricular pacing on the right ventricular septum. | Procedure: pacemaker implantation, AAI(R)-DDD(R) versus DDD(R)<br>* Indication for pacemaker implantation: sick sinus syndrome in conformity with the current guidelines. Only market-released CE certified 2-chamber cardiac pacemakers and electrodes are used. The implantation is done according to the applicable standards. Active RV-lead is positioned on the right ventricular septum.<br>* Other names: DDD(R);|
| AAI(R)<=>DDD(R)<br>SSS, PM-mode programmed for minimizing right ventricular pacing on the right interventricular septum | Procedure: pacemaker implantation, AAI(R)-DDD(R) versus DDD(R)<br>* Indication for pacemaker implantation: sick sinus syndrome in conformity with the current guidelines. Only market-released CE certified 2-chamber cardiac pacemakers and electrodes are used. The implantation is done according to the applicable standards. Active RV-lead is positioned on the right ventricular septum.<br>* Other names: DDD(R);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| end-systolic LV volume |  | at randomisation and after 12 months | 
| left ventricular ejection fraction (LV-EF) | TTE, Simpson, biplane | at randomisation and after 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TAPSE |  | at randomisation and after 12 months | 
| echocardiographic parameter of dyssynchrony | TTE, SPWMD, LV-PEP, IVMD | at randomisation and after 12 months | 
| peak VO2, VO2 AT, VO2/HR, VE/VCO2 slope | CPX: cardiopulmonary exercice testing | at randomisation and after 12 months | 
| quality of life-scores | SF-36 | at randomisation and after 12 months | 
| AF burden |  | at randomisation and after 12 months | 
| % ventricular pacing |  | at randomisation and after 12 months | 
| LV end diastolic volume | TTE | at randomisation and after 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sick Sinus Syndrome, Cardiac Pacing, Artificial, Cardiac Resynchronization Therapy, Pacemaker, Artificial, SSS