RV Septal Versus Minimized RV Pacing in Sick Sinus Syndrome

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)

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)

Eligibility Criteria:
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