rv septal versus minimized rv pacing in sick sinus syndrome

Conditions: Sick Sinus Syndrome

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)

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

Keywords: sick sinus syndrome cardiac pacing, artificial cardiac resynchronization therapy pacemaker, artificial sss