The SEPTAL CRT study (NCT: )

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1 Comparison of right ventricular septal pacing and right ventricular apical pacing in patients receiving cardiac resynchronization therapy defibrillators The SEPTAL CRT study (NCT: ) Christophe Leclercq, Nicolas Sadoul, Luis Mont, Pascal Defaye, Joaquím Osca, Marc Delay, Gilbert Habib, Elisabeth Mouton, Jose Zamorano, Ignacio Lozano, on behalf of the Septal CRT Study investigators 2014 ESC congress, Barcelona, September 1 st, 2014 The SEPTAL CRT study was supported by grants from Boston Scientific

2 Disclosure Information Christophe Leclercq, MD, PhD Research Grants: Boston Scientific, Medtronic, Sorin Group, St. Jude Medical, Consulting / Advisory board: Boston Scientific, Biotronik, Medtronic, St. Jude Medical, Sorin Group Lectures: Boston Scientific, Biotronik, Medtronic, St. Jude Medical, Sorin Group, GE, Boehringer, Bayer, BMS 2

3 Background CRT is a recommended therapeutic strategy in symptomatic HF patients with depressed LVEF and wide QRS Clinical or echocardiographic success is achieved in a maximum of 2/3 of the patients. Apical position is conventional for the RV lead but may affect cardiac function RV mid-septal position has been proposed as an alternative position to improve CRT efficiency However, the benefits of the RV mid-septal lead location are uncertain and have not so far been assessed in a prospective multicenter randomized clinical trial 3

4 Aims of the SEPTAL CRT Study Non inferiority hypothesis To compare the effects of the RV lead position, apical (RVA) or mid-septal (RVMS) on the LV reverse remodeling at 6 months in patients receiving a CRT-D To evaluate the 1 year clinical outcome To evaluate the safety 4

5 Primary and Main Secondary Endpoints Primary endpoint: Changes in the LVESV between baseline and 6 months Secondary endpoints: the percentage of echo-responders defined by a reduction in the LVESV > 15% at 6 months the implant success rate of the RV lead the proportion of patients experiencing 1 MAE, including deaths from all causes, serious cardiac AE procedure-related or device-related MAE 5

6 Study Design Prospective, multicenter, European, single-blind, randomized controlled trial: 1:1 randomization Apical vs. mid-septal RV location In office visits after implant at 1, 6 and 12 months Designed to detect the non-inferiority in the primary endpoint with: A 90% power At the 2.5% unilateral significance level Per protocol (PP) population analysis by use of the lower limit of the confidence interval of the difference in the reduction of LVESV between treatments with a cut-off value of - 20 ml Sample size requirement of 240 patients 25 Centers: 19 in France (173 patients), 9 in Spain (90 patients) 6

7 Patients 18 years Inclusion Criteria Indications for de novo CRT-D implantation according to 2008 ESC Guidelines LVEF 35% Stable NYHA class III or ambulatory class IV Stable sinus rhythm and QRS 120 ms No HF hospitalization within 1 month prior enrolment Inclusion criteria amended in 2009 Extension to NYHA class II with QRS 150 ms 7

8 RV Lead Implant RV lead implanted, Endotak Reliance, in the RVA or RVS according to randomization RVA: lead advanced as far as possible towards the apex RVMS: optimal lead position Oriented frontally and towards the left in LAO projection Electrical criteria to be fulfilled: Pacing threshold < 1.5 V/0.5 ms R wave > 5.0 mv Lead impedance between 450 and 1800 Ω 1 successful DFT with a 10 J safety margin Criteria not met 2 nd attempt in an adjacent position was performed. In case of failure, the lead was repositioned at the alternative site and tested. All X-rays were analyzed by two physicians 8

9 RV Lead Implant Apical Mid-septal AP view LAO view 9

10 Echocardiographic parameters Parameters recorded at baseline, 6 and 12 months: Volumes : LVESV, LVEDV Diameters : LVESD and LVEDD Function : LVEF (Simpson s method) Dyssynchrony echocardiographic parameters LV filling time, Right and left pre ejections delays and interventricular mechanical delay Independent echocardiographic core lab (Dr G. Derumeaux, MD, University Hospital, Créteil, France) 10

11 Study flowchart 263 randomized patients ITT population (RVA: 132 pts / RVMS: 131 pts) 231 patients end of FU Death = 9 Lost to FU = 23 RVA: 11 / RVMS : 12 Echo non analyzable = 49 RVA: 26 / RVMS: patients with all echo data PP population (RVA: 92 pts / RVMS: 90 pts) 11

12 Baseline Characteristics ITT Population RVA (132) RVMS (131) Total (263) Men (%) Age, (y) 63.8 ± ± ± 9.5 NYHA class II (%) NYHA class III (%) NYHA class IV ambulatory (%) Ischemic cardiomyopathy (%) LVEF (%) 30± 7 30± 8 30± 8 Baseline medication : Diuretics (%) ACE inhibitor or ARB (%) Aldosterone antagonist (%) Beta-blocker (%) Primary prevention (%) QRS duration, ms ± ± ± 22.1 No significant difference between RA and RVMS populations for all parameters

13 Baseline Characteristics PP Population RVA (92) RVMS (90) Total (182) Men (%) Age, (y) 64.1 ± ± ± 9.8 NYHA class II (%) NYHA class III (%) NYHA class IV ambulatory (%) Ischemic cardiomyopathy (%) LVEF (%) 30 ± 8 30 ± 8 30 ± 8 Baseline medication : Diuretics (%) ACE inhibitor or ARB (%) Aldosterone antagonist (%) Beta-blocker (%) Primary prevention (%) QRS duration, ms ± ± ± 21.2 No significant difference between ITT and PP populations for all parameters

14 Results : Primary Endpoint RVA (n=92) RVMS (n=90). LVESV baseline (ml) ± ± 83 LVESV 6 months (ml) ± ± 86 Difference (ml) ± 44 p : < ± 39 p : <

15 Results : Primary Endpoint RVA (n=92) RVMS (n=90) LVESV baseline (ml) ± ± 83 LVESV 6 months (ml) ± ± 86 Difference (ml) ± ± 39 PP analysis : Mean difference in LVESV reduction: ml with lower limit of the unilateral 97.5% confidence interval at ml (p= 0.006) Per-protocol analysis p = Non-inferiority margin

16 Results : Primary Endpoint RVA (n=92) RVMS (n=90) LVESV baseline (ml) ± ± 83 LVESV 6 months (ml) ± ± 86 Difference (ml) ± ± 39 ITT analysis : mean difference in LVESV reduction: -5.2 ml with lower limit of the unilateral 97.5% confidence interval at ml (p= 0.006) Per-protocol analysis p = Intent to treat analysis p = Non-inferiority margin

17 Results : Primary Endpoint RVA (n=92) RVMS (n=90) p LVESV baseline (ml) LVESV 6 months (ml) Difference (ml) ± ± ± ± ± ± As non inferiority reached Superiority analysis No significant difference between the two populations 17

18 Main Secondary Endpoints No in the percentage of echo-responders, i.e. reduction in LVESV > 15% at 6 months, 50% in both groups, p = 0.99 No in RV lead pre-specified electrical criteria 90.0% in the Septum randomized group 86.8% in the Apex randomized group Mostly due to the lack of defibrillation testing (n = 27) 2 patients crossed over due to failure of fulfilling the RV implantation criteria in each group 18

19 Echo Measures from Baseline to 6 months RVA (N=92) RVMS (N=90) RVM Svs. RVA VARIABLE Baseline 6 Months Change Baseline 6 Months Change P LVESD (mm) 62.0 ± ± ± ± ± ± LVEDD (mm) 72.2 ± ± ± ± ± ± LVESV (ml) ± ± ± ± ± ± LVEDV (ml) ± ± ± ± ± ± LVEF (%) 30.0 ± ± ± ± ± ± LV filling time (ms) ± ± ± ± ± ± No significant difference between RA and RVMS populations for all parameters 19

20 1-year Mortality Deaths, n(%) RVA (132) RVMS (131) Total (263) - Cardiac Heart failure 4 2 (1.5%) 2 1 (0.8%) 6 3 EMD 1 (0.8%) 0 1 Myocardial infarction - Non-cardiac Stroke 1 (0.8%) (0.8%) 3 1 (0.8%) Pancreatitis 0 1 (0.8%) 1 Intestinal occlusion 0 1 (0.8%) 1 TOTAL 4 (3.0%) 5 (3,8%) 9 (3.4%) No death related to the RV lead No significant difference between RVA and RVMS vs. populations for mortality 20

21 1-year Mortality

22 Time to First HF Hospitalization or Death

23 Procedure or Device-Related MAE RVA N=132 RMVS N=131 RVMS vs. RVA RV lead 4 (3.0%) 3 (2.3%) P= Atrial lead 2 (1.5%) 4 (3.1%) P= LV lead 15 (11.4%) 15 (11.5%) P= CRT-D ( Recall) 0 (0.0%) 1 (0.8%) P= CRT-D (Reinsertion) 1 (0.8%) 4 (3.1%) P= Pocket Hematoma 4 (3.0%) 4 (3.1%) P= Infection 1 (0.8%) 3 (2.3%) P= Others 10 (7.5%) 7 (5.3%) P= Total 31 (23.5%) 37 (28.2%) P= 0.41 No significant difference between the RVMS and RVA populations 23

24 Conclusions First multicenter randomized prospective trial comparing RV apical and RV septal pacing in CRT-D recipients Septal CRT demonstrates the non-inferiority of RV midseptal pacing when compared to conventional RV apical pacing in CRT patients ü No in LVESV reduction between baseline and 6 months ü Similar percentage of echo-responders (50%) ü No difference in implant success rate No statistical for the safety and efficacy endpoints: ü Total mortality: 3.0% vs.3.8% (p=0.749) ü MAE : 34.8% vs. 39.7% (p=0.446) 24

25 Lille Rouen St Denis Rennes Paris Nancy Angers Nantes Lyon Bordeaux Grenoble Montpellier Toulouse (2) Marseille (2) Valladolid Madrid Toledo Sevilla Malaga Valencia Alicante Barcelona (2) Steering committee: C. Leclercq, I.Lozano G.Habib, R.Isnard, L.Mont, J. Osca, N.Sadoul 25