Electrophysiologically Guided PAcing Site Selection Study (EPASS)

Investigational New Drug Application/ Investigational Device Exemption Information

This study is a long-term, prospective, and controlled evaluation of the incidence of persistent atrial fibrillation (AF) in patients with severe intra-right atrial conduction delay paced with preventive algorithms at the interatrial septum (IAS) versus right atrial appendage (RAA).

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation; Sinus Arrhythmia
• Intervention / Treatment: Procedure: IAS pacing - study group; Procedure: IAS pacing control group; Procedure: Pacing RAA study group; Procedure: Pacing RAA control group

Detailed Description

The EPASS is a multicenter, prospective, randomized, and controlled study.

Prior to entering the study, the patient should be informed and provide a written consent. In addition, the patient should meet all selection criteria. The Investigator has to check that all selection criteria are satisfied. Then the patient undergoes pacemaker implantation, receiving a pacemaker model T70 or Selection 9000 (or later version).

Patients eligible for the study are enrolled and submitted to the evaluation of intra-light atrial conduction delay before device implantation. Besides, they are assigned to the group with severe RA conduction delay or with normal conduction delay. The randomization of the pacing site for both groups depends on the value of right atrial conduction delay, together with the associated diseases of the patients, sex and age. After implantation, a stabilization phase of 3-5 weeks is required to stabilize the leads: during this period the physician can optimize the device parameters. Neither the data regarding AF episodes nor cardioversion are collected.

At the end of the stabilization phase the patient undergoes the 1st study follow-up and starts the monitoring period lasting 2 years. Regular follow-ups and data collection are scheduled every 6 months.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Borgomanero, Italy, 28100
    • Divisione di Cardiologia - Presidi Ospedalieri Riuniti
  • BS
    • Desenzano, BS, Italy
      • Azienda Ospedaliera di Desenzano del Garda
  • CO
    • Como, CO, Italy, 22100
      • Divisione di Cardiologia
  • PI
    • Pisa, PI, Italy, 56127
      • Divisione di Cardiologia - CRN
    • Pisa, PI, Italy, 56127
      • Divisione di Cardiologia - Ospedale Cisanello
  • Prato
    • Fucecchio, Prato, Italy
      • Divisione di Cardiologia - Ospedale San Pietro Igneo
  • TO
    • Torino, TO, Italy, 10126
      • Divisione di Cardiologia - Ospedale Molinette
  • VE
    • Mirano, VE, Italy, 30035
      • Divisione di Cardiologia - Ospedale Civile ULSS 13

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Symptomatic sinus node dysfunction
• More than 18 years old
• Signed informed consent

Exclusion Criteria:

• Less than 18 years old
• Pregnancy
• Anamnestic transient ischemic attack (TIA) or stroke
• Neoplastic or any other severe disease reducing life expectancy
• Heart surgery in the last 3 months
• Left atrial diameter > 55mm, determined in the parasternal long-axis view (during either sinus rhythm or atrial fibrillation)
• Participation in other studies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1. IAS pacing - study group; Patients were first submitted to electrophysiological study to assess Delta CTos > or < 50 ms. Then they were randomized to interatrial septum pacing od right atrial appendage. This arm (1) includes patients with Delta CTos >50 ms and randomized IAS pacing. IAS Pacing -Study Group: Patients with Delta CTos >50 ms (study group) at the electrophysiologic study and randomized Interatrial Septum Pacing	Procedure: IAS pacing - study group; site of implant and permanent pacing
Experimental: 2. IAS pacing-control group; (Delta CTos<50ms) Patients were first submitted to electrophysiological study to assess Delta CTos > or < 50 ms. Then they were randomized to interatrial septum pacing od right atrial appendage. This arm (2) includes patients with Delta CTos <50 ms and randomized IAS pacing. IAS Pacing -Control Group: Patients with Delta CTos <50 ms (control group) at the electrophysiologic study and randomized Interatrial Septum Pacing	Procedure: IAS pacing control group; site of implant and permanent pacing
Active Comparator: 3. RAA Pacing - study group; Patients were first submitted to electrophysiological study to assess Delta CTos > or < 50 ms. Then they were randomized to interatrial septum pacing od right atrial appendage. This arm (3) includes patients with Delta CTos >50 ms and randomized Right Atrial Appendage pacing. RAA Pacing -Study Group: Patients with Delta CTos >50 ms (study group) at the electrophysiologic study and randomized Right Atrial Appendage pacing	Procedure: Pacing RAA study group; site of implant and permanent pacing
Active Comparator: 4. RAA Pacing - control group; Patients were first submitted to electrophysiological study to assess Delta CTos > or < 50 ms. Then they were randomized to interatrial septum pacing od right atrial appendage. This arm (4) includes patients with Delta CTos <50 ms and randomized Right Atrial Appendage pacing. RAA Pacing -Control Group: Patients with Delta CTos <50 ms (control group) at the electrophysiologic study and randomized Right Atrial Appendage pacing	Procedure: Pacing RAA control group; site of implant and permanent pacing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Persistent Atrial Fibrillation (AF) After a Mean Follow-up of 15±7 Months: Comparison Between IAS and RAA Pacing in the Study Group	Persistent Atrial Fibrillation (AF) incidence	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Persistent Atrial Fibrillation (AF) Episodes: Comparison Between All Groups	January 2009
Number of Patients With Permanent Atrial Fibrillation (AF)	January 2009
Symptom Scale Questionnaire: Comparison Between All Groups	January 2009
Number of Cardioversion: Comparison Between All Groups	January 2009
Heart Failure: Comparison Between All Groups	January 2009
Time to First Persistent Episode of Atrial Fibrillation (AF)	January 2009
Number of Episodes/Day	January 2009
AF Burden	January 2009
Ventricular Pacing Percentage	January 2009

Collaborators and Investigators

• Sponsor: Medtronic BRC
• Collaborators: Medtronic
• Investigators: Study Director: Giorgio Corbucci, PhD, Medtronic; Principal Investigator: Roberto Verlato, MD, Camposampiero Hospital

Publications and helpful links

General Publications

• Rosenqvist M, Brandt J, Schuller H. Long-term pacing in sinus node disease: effects of stimulation mode on cardiovascular morbidity and mortality. Am Heart J. 1988 Jul;116(1 Pt 1):16-22. doi: 10.1016/0002-8703(88)90244-x.
• Stangl K, Seitz K, Wirtzfeld A, Alt E, Blomer H. Differences between atrial single chamber pacing (AAI) and ventricular single chamber pacing (VVI) with respect to prognosis and antiarrhythmic effect in patients with sick sinus syndrome. Pacing Clin Electrophysiol. 1990 Dec;13(12 Pt 2):2080-5. doi: 10.1111/j.1540-8159.1990.tb06946.x.
• Santini M, Alexidou G, Ansalone G, Cacciatore G, Cini R, Turitto G. Relation of prognosis in sick sinus syndrome to age, conduction defects and modes of permanent cardiac pacing. Am J Cardiol. 1990 Mar 15;65(11):729-35. doi: 10.1016/0002-9149(90)91379-k.
• Sgarbossa EB, Pinski SL, Maloney JD, Simmons TW, Wilkoff BL, Castle LW, Trohman RG. Chronic atrial fibrillation and stroke in paced patients with sick sinus syndrome. Relevance of clinical characteristics and pacing modalities. Circulation. 1993 Sep;88(3):1045-53. doi: 10.1161/01.cir.88.3.1045.
• Andersen HR, Nielsen JC, Thomsen PE, Thuesen L, Mortensen PT, Vesterlund T, Pedersen AK. Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome. Lancet. 1997 Oct 25;350(9086):1210-6. doi: 10.1016/S0140-6736(97)03425-9.
• Connolly SJ, Kerr CR, Gent M, Roberts RS, Yusuf S, Gillis AM, Sami MH, Talajic M, Tang AS, Klein GJ, Lau C, Newman DM. Effects of physiologic pacing versus ventricular pacing on the risk of stroke and death due to cardiovascular causes. Canadian Trial of Physiologic Pacing Investigators. N Engl J Med. 2000 May 11;342(19):1385-91. doi: 10.1056/NEJM200005113421902.
• Attuel P, Pellerin D, Mugica J, Coumel P. DDD pacing: an effective treatment modality for recurrent atrial arrhythmias. Pacing Clin Electrophysiol. 1988 Nov;11(11 Pt 2):1647-54. doi: 10.1111/j.1540-8159.1988.tb06289.x.
• 8. Daubert C, Mabo B, Berder V. Arrhythmia prevention by permanent atrial resynchronization in advanced interatrial block. Eur Heart J 1990;11: 237-42.
• Saksena S, Prakash A, Hill M, Krol RB, Munsif AN, Mathew PP, Mehra R. Prevention of recurrent atrial fibrillation with chronic dual-site right atrial pacing. J Am Coll Cardiol. 1996 Sep;28(3):687-94. doi: 10.1016/0735-1097(96)00232-x.
• Delfaut P, Saksena S, Prakash A, Krol RB. Long-term outcome of patients with drug-refractory atrial flutter and fibrillation after single- and dual-site right atrial pacing for arrhythmia prevention. J Am Coll Cardiol. 1998 Dec;32(7):1900-8. doi: 10.1016/s0735-1097(98)00489-6.
• 11. Prakash A, Giorgberidze I. Endocardial mapping of sites of conduction delay for atrial premature beats in patients with atrial fibrillation. PACE 1997;20 (part II):1161.
• Papageorgiou P, Monahan K, Boyle NG, Seifert MJ, Beswick P, Zebede J, Epstein LM, Josephson ME. Site-dependent intra-atrial conduction delay. Relationship to initiation of atrial fibrillation. Circulation. 1996 Aug 1;94(3):384-9. doi: 10.1161/01.cir.94.3.384.
• Cosio FG, Palacios J, Vidal JM, Cocina EG, Gomez-Sanchez MA, Tamargo L. Electrophysiologic studies in atrial fibrillation. Slow conduction of premature impulses: a possible manifestation of the background for reentry. Am J Cardiol. 1983 Jan 1;51(1):122-30. doi: 10.1016/s0002-9149(83)80022-8.
• Padeletti L, Porciani MC, Michelucci A, Colella A, Ticci P, Vena S, Costoli A, Ciapetti C, Pieragnoli P, Gensini GF. Interatrial septum pacing: a new approach to prevent recurrent atrial fibrillation. J Interv Card Electrophysiol. 1999 Mar;3(1):35-43. doi: 10.1023/a:1009867305678.
• Padeletti L, Purerfellner H, Adler SW, Waller TJ, Harvey M, Horvitz L, Holbrook R, Kempen K, Mugglin A, Hettrick DA; Worldwide ASPECT Investigators. Combined efficacy of atrial septal lead placement and atrial pacing algorithms for prevention of paroxysmal atrial tachyarrhythmia. J Cardiovasc Electrophysiol. 2003 Nov;14(11):1189-95. doi: 10.1046/j.1540-8167.2003.03191.x.
• Stabile G, Senatore G, De Simone A, Turco P, Coltorti F, Nocerino P, Vitale DF, Chiariello M. Determinants of efficacy of atrial pacing in preventing atrial fibrillation recurrences. J Cardiovasc Electrophysiol. 1999 Jan;10(1):2-9. doi: 10.1111/j.1540-8167.1999.tb00635.x.
• De Sisti A, Attuel P, Manot S, Fiorello P, Halimi F, Leclercq JF. Electrophysiological characteristics of the atrium in sinus node dysfunction with and without postpacing atrial fibrillation. Pacing Clin Electrophysiol. 2000 Mar;23(3):303-8. doi: 10.1111/j.1540-8159.2000.tb06753.x.
• Leclercq JF, De Sisti A, Fiorello P, Halimi F, Manot S, Attuel P. Is dual site better than single site atrial pacing in the prevention of atrial fibrillation? Pacing Clin Electrophysiol. 2000 Dec;23(12):2101-7. doi: 10.1111/j.1540-8159.2000.tb00783.x.
• 19. Attuel P, Pellerin D, Gaston J et al: Latent atrial vulnerability: new means of electrophysiologic investigation in atrial arrhythmias. In Attuel P, Coumel P, Janse M,eds:The Atrium in Health and Disease.Futura Publishing Co.,Inc.,Mt.Kisco,NY,1989,pp159-200.
• Becker R, Klinkott R, Bauer A, Senges JC, Schreiner KD, Voss F, Kuebler W, Schoels W. Multisite pacing for prevention of atrial tachyarrhythmias: potential mechanisms. J Am Coll Cardiol. 2000 Jun;35(7):1939-46. doi: 10.1016/s0735-1097(00)00631-8.
• Duytschaever M, Danse P, Eysbouts S, Allessie M. Is there an optimal pacing site to prevent atrial fibrillation?: an experimental study in the chronically instrumented goat. J Cardiovasc Electrophysiol. 2002 Dec;13(12):1264-71. doi: 10.1046/j.1540-8167.2002.01264.x.
• Bailin SJ, Adler S, Giudici M. Prevention of chronic atrial fibrillation by pacing in the region of Bachmann's bundle: results of a multicenter randomized trial. J Cardiovasc Electrophysiol. 2001 Aug;12(8):912-7. doi: 10.1046/j.1540-8167.2001.00912.x.
• Hermida JS, Carpentier C, Kubala M, Otmani A, Delonca J, Jarry G, Rey JL. Atrial septal versus atrial appendage pacing: feasibility and effects on atrial conduction, interatrial synchronization, and atrioventricular sequence. Pacing Clin Electrophysiol. 2003 Jan;26(1 Pt 1):26-35. doi: 10.1046/j.1460-9592.2003.00146.x.
• Padeletti L, Michelucci A, Pieragnoli P, Colella A, Musilli N. Atrial septal pacing: a new approach to prevent atrial fibrillation. Pacing Clin Electrophysiol. 2004 Jun;27(6 Pt 2):850-4. doi: 10.1111/j.1540-8159.2004.00546.x.
• Duytschaever M, Firsovaite V, Colpaert R, Allessie M, Tavernier R. Limited benefit of septal pre-excitation in pace prevention of atrial fibrillation. J Cardiovasc Electrophysiol. 2005 Mar;16(3):269-77. doi: 10.1046/j.1540-8167.2005.40435.x.
• Verlato R, Botto GL, Massa R, Amellone C, Perucca A, Bongiorni MG, Bertaglia E, Ziacchi V, Piacenti M, Del Rosso A, Russo G, Baccillieri MS, Turrini P, Corbucci G. Efficacy of low interatrial septum and right atrial appendage pacing for prevention of permanent atrial fibrillation in patients with sinus node disease: results from the electrophysiology-guided pacing site selection (EPASS) study. Circ Arrhythm Electrophysiol. 2011 Dec;4(6):844-50. doi: 10.1161/CIRCEP.110.957126. Epub 2011 Sep 23.

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: October 13, 2005
• First Submitted That Met QC Criteria: October 13, 2005
• First Posted (Estimate): October 14, 2005

Study Record Updates

• Last Update Posted (Estimate): November 25, 2013
• Last Update Submitted That Met QC Criteria: September 20, 2013
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: atrial fibrillation; interatrial septum; atrial pacing; symptomatic sinus node dysfunction,; pacemaker indication class I
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Arrhythmia, Sinus
• Other Study ID Numbers: EPASS