The Substrate and Intervention Mechanisms for Persistent Atrial Fibrillation Trial

NCT02918396 | Terminated Results

• 1 other identifier: IRB00084915
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia with increasing morbidity and mortality. A catheter-based AF ablation technique that isolates pulmonary veins (PV) from the left atrium has been established to disrupt AF. Despite significant development, AF ablation with pulmonary vein isolation (PVI) is reported to have a success rate of 40-80% in various AF populations. Persistent AF appears to be more reliant upon fibroblast proliferation and myocyte-fibroblast coupling than paroxysmal AF with obvious implications on its management. Despite the knowledge that fibrotic substrate is responsible for the perpetuation of persistent AF, several ablation techniques targeting these extra-pulmonary veins sites have failed to prove an additional benefit to PVI alone. Nevertheless, two recently developed technologies, aimed at detecting AF substrate with high precision, seem to constitute a potential breakthrough in the management of persistent AF. On one hand, late gadolinium-enhanced MRI (LGE-MRI) is a well-established method to identify fibrosis in the myocardium. Recent reports from a single center have shown that MRI-based left atrial fibrosis detection is able to predict the outcome of the procedure. Hence, targeting lesions seen on LGE-MRI in the setting of persistent AF is an option yet to be explored and compared to the widely adopted, yet suboptimal, PVI. On another hand, a novel ablation method with promising results is focal impulse and rotor modulation (FIRM). Undergoing wide sampling of the atria with spatiotemporal and computational mapping while in AF has identified areas with stable organized rotational electrical activity (rotors). Several studies are under way to prove the reproducibility of rotor mapping, with more groups reporting improved rates of acute and long-term suppression of AF with ablation of FIRM-identified rotors. The SIMPle AF study will be a randomized clinical trial designed to test the hypothesis that ablation tailored to the underlying substrate using either LGE-detected dense scar or rotor anchor sites predicted by computational modeling is superior to anatomic non-tailored PVI ablation in patients with persistent AF. For the present study, the investigators plan to enroll a total of 30 patients.

Conditions

Persistent Atrial Fibrillation

Keywords

Atrial Fibrillation; Atrial Fibrosis; Late Gadolinium Enhancement Magnetic Resonance Imaging; Computational Modeling; Rotor Anchor Sites

Outcome Measures

Primary Outcomes (1)

• Recurrence of Atrial Fibrillation (AF) > 30 Seconds

  Primary outcome is defined as symptomatic or asymptomatic AF of at least 30 seconds duration that is documented by an ECG or mobile rhythm monitoring device (AliveCor), occurring after the 3-month blanking period following catheter ablation and up to 12 months.

  Following the 90 day blanking period up to 12 months post-index pulmonary vein isolation

Study Arms (3)

Conventional PVI

ACTIVE COMPARATOR

Conventional PVI by Radio-frequency Ablation: Wide area circumferential pulmonary vein isolation (PVI) only (current standard of care) using radio-frequency ablation catheters.

Device: Conventional PVI by Radio-frequency Ablation

PVI + Scar-based ablation

EXPERIMENTAL

Scar-Based Radio-frequency Ablation: Pulmonary vein isolation followed by targeting, using radio-frequency ablation, of dense LGE sites on MRI, which are confirmed on bipolar mapping to have voltage \<0.3 mV.

Device: Scar-Based Radio-frequency Ablation

PVI + Modeling-predicted rotors ablation

EXPERIMENTAL

Rotor Anchors Radio-frequency Ablation: Pulmonary vein isolation followed by radio-frequency ablation of rotor anchors predicted by modeling.

Device: Rotor Anchors Radio-frequency Ablation

Interventions

Scar-Based Radio-frequency Ablation DEVICE

Left atrial (LA) myocardium will be manually segmented prior to the procedure and 3D-volumes of the atrial anatomy with superimposed dense LGE maps will be generated. Prior to the PVI, a dense voltage map of the left atrium will be performed (\>1000 points) iin sinus rhythm. After PVI, low voltage areas (defined as \<0.3 mV) which are superimposed on dense LGE on the MRI will be targeted by radio frequency ablation with a contact force sensing, irrigated radiofrequency catheter approved by FDA for the treatment of atrial fibrillation.

PVI + Scar-based ablation

Rotor Anchors Radio-frequency Ablation DEVICE

Left atrial (LA) myocardium will be manually segmented prior to the procedure and the LA shell, along with the LGE-MRI will be sent to the biomedical engineering team who will generate a 3D-model of the LA along with rotor anchor sites predicted by modeling. After the PVI, the 3D models will be displayed and the rotor anchor sites will be targeted by radiofrequency ablation with a contact force sensing, irrigated radiofrequency catheter approved by FDA for the treatment of atrial fibrillation.

PVI + Modeling-predicted rotors ablation

Conventional PVI by Radio-frequency Ablation DEVICE

Conventional wide area circumferential ablation (WACA) pulmonary vein isolation will be performed using a contact-force sensing, irrigated radiofrequency catheter approved by FDA for the treatment of atrial fibrillation.

Conventional PVI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of persistent atrial fibrillation
• Indicated for an AF-ablation procedure
• Agree to participate in the trial

You may not qualify if:

• Are unable or unwilling to provide informed consent for the SIMPle AF study
• Patients with cardiac devices like pacemakers, internal cardiac defibrillators and Cardiac Resynchronization Therapy Device (CRT). Patients with acute or chronic renal insufficiency (glomerular filtration rate \<30 ml/min/1.73 m2), or patients in the perioperative liver transplantation period
• Pregnant women
• Patients who are unable to adhere to the follow up protocol
• Patients with contraindication to MRI, including ferromagnetic aneurysm clips, metal in the eye, and implanted ferromagnetic or other MRI-incompatible devices
• Patients in whom the LGE Cardiac MRI does not meet quality standards for fibrosis analysis
• Subjects without daily access to a smart phone or tablet compatible with the mobile-based application and ability to upload ECG tracings for the follow up period
• Patients with a history of allergic reactions to gadolinium-based contrast agents or ingredients and will not be premedicated\*\*
• Subjects with a history of reaction to contrast may be premedicated according to institutional protocol prior to receiving intravenous contrast agents

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Related Publications (20)

• Akoum N, Marrouche N. Assessment and impact of cardiac fibrosis on atrial fibrillation. Curr Cardiol Rep. 2014 Aug;16(8):518. doi: 10.1007/s11886-014-0518-z.

  PMID: 24950676 BACKGROUND

• Akoum N, Morris A, Perry D, Cates J, Burgon N, Kholmovski E, MacLeod R, Marrouche N. Substrate Modification Is a Better Predictor of Catheter Ablation Success in Atrial Fibrillation Than Pulmonary Vein Isolation: An LGE-MRI Study. Clin Med Insights Cardiol. 2015 Apr 27;9:25-31. doi: 10.4137/CMC.S22100. eCollection 2015.

  PMID: 25983561 BACKGROUND

• Benjamin EJ, Wolf PA, D'Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998 Sep 8;98(10):946-52. doi: 10.1161/01.cir.98.10.946.

  PMID: 9737513 BACKGROUND

• Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, Crijns HJ, Damiano RJ Jr, Davies DW, DiMarco J, Edgerton J, Ellenbogen K, Ezekowitz MD, Haines DE, Haissaguerre M, Hindricks G, Iesaka Y, Jackman W, Jalife J, Jais P, Kalman J, Keane D, Kim YH, Kirchhof P, Klein G, Kottkamp H, Kumagai K, Lindsay BD, Mansour M, Marchlinski FE, McCarthy PM, Mont JL, Morady F, Nademanee K, Nakagawa H, Natale A, Nattel S, Packer DL, Pappone C, Prystowsky E, Raviele A, Reddy V, Ruskin JN, Shemin RJ, Tsao HM, Wilber D. 2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design. Europace. 2012 Apr;14(4):528-606. doi: 10.1093/europace/eus027. Epub 2012 Mar 1. No abstract available.

  PMID: 22389422 BACKGROUND

• Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ, Gillum RF, Kim YH, McAnulty JH Jr, Zheng ZJ, Forouzanfar MH, Naghavi M, Mensah GA, Ezzati M, Murray CJ. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation. 2014 Feb 25;129(8):837-47. doi: 10.1161/CIRCULATIONAHA.113.005119. Epub 2013 Dec 17.

  PMID: 24345399 BACKGROUND

• Dorian P, Cvitkovic SS, Kerr CR, Crystal E, Gillis AM, Guerra PG, Mitchell LB, Roy D, Skanes AC, Wyse DG. A novel, simple scale for assessing the symptom severity of atrial fibrillation at the bedside: the CCS-SAF scale. Can J Cardiol. 2006 Apr;22(5):383-6. doi: 10.1016/s0828-282x(06)70922-9.

  PMID: 16639472 BACKGROUND

• Estes NA 3rd, Sacco RL, Al-Khatib SM, Ellinor PT, Bezanson J, Alonso A, Antzelevitch C, Brockman RG, Chen PS, Chugh SS, Curtis AB, DiMarco JP, Ellenbogen KA, Epstein AE, Ezekowitz MD, Fayad P, Gage BF, Go AS, Hlatky MA, Hylek EM, Jerosch-Herold M, Konstam MA, Lee R, Packer DL, Po SS, Prystowsky EN, Redline S, Rosenberg Y, Van Wagoner DR, Wood KA, Yue L, Benjamin EJ. American Heart Association atrial fibrillation research summit: a conference report from the American Heart Association. Circulation. 2011 Jul 19;124(3):363-72. doi: 10.1161/CIR.0b013e318224b037. Epub 2011 Jun 27. No abstract available.

  PMID: 21709057 BACKGROUND

• Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Le Mouroux A, Le Metayer P, Clementy J. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med. 1998 Sep 3;339(10):659-66. doi: 10.1056/NEJM199809033391003.

  PMID: 9725923 BACKGROUND

• Inoue K, Kurotobi T, Kimura R, Toyoshima Y, Itoh N, Masuda M, Higuchi Y, Date M, Koyama Y, Okamura A, Iwakura K, Fujii K. Trigger-based mechanism of the persistence of atrial fibrillation and its impact on the efficacy of catheter ablation. Circ Arrhythm Electrophysiol. 2012 Apr;5(2):295-301. doi: 10.1161/CIRCEP.111.964080. Epub 2011 Oct 31.

  PMID: 22042883 BACKGROUND

• Marrouche NF, Wilber D, Hindricks G, Jais P, Akoum N, Marchlinski F, Kholmovski E, Burgon N, Hu N, Mont L, Deneke T, Duytschaever M, Neumann T, Mansour M, Mahnkopf C, Herweg B, Daoud E, Wissner E, Bansmann P, Brachmann J. Association of atrial tissue fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: the DECAAF study. JAMA. 2014 Feb 5;311(5):498-506. doi: 10.1001/jama.2014.3.

  PMID: 24496537 BACKGROUND

• McGann C, Akoum N, Patel A, Kholmovski E, Revelo P, Damal K, Wilson B, Cates J, Harrison A, Ranjan R, Burgon NS, Greene T, Kim D, Dibella EV, Parker D, Macleod RS, Marrouche NF. Atrial fibrillation ablation outcome is predicted by left atrial remodeling on MRI. Circ Arrhythm Electrophysiol. 2014 Feb;7(1):23-30. doi: 10.1161/CIRCEP.113.000689. Epub 2013 Dec 20.

  PMID: 24363354 BACKGROUND

• Narayan SM, Baykaner T, Clopton P, Schricker A, Lalani GG, Krummen DE, Shivkumar K, Miller JM. Ablation of rotor and focal sources reduces late recurrence of atrial fibrillation compared with trigger ablation alone: extended follow-up of the CONFIRM trial (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation). J Am Coll Cardiol. 2014 May 6;63(17):1761-8. doi: 10.1016/j.jacc.2014.02.543. Epub 2014 Mar 13.

  PMID: 24632280 BACKGROUND

• Narayan SM, Krummen DE, Shivkumar K, Clopton P, Rappel WJ, Miller JM. Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation) trial. J Am Coll Cardiol. 2012 Aug 14;60(7):628-36. doi: 10.1016/j.jacc.2012.05.022. Epub 2012 Jul 18.

  PMID: 22818076 BACKGROUND

• Runge VM. Safety of magnetic resonance contrast media. Top Magn Reson Imaging. 2001 Aug;12(4):309-14. doi: 10.1097/00002142-200108000-00007.

  PMID: 11687717 BACKGROUND

• Schenck JF. Safety of strong, static magnetic fields. J Magn Reson Imaging. 2000 Jul;12(1):2-19. doi: 10.1002/1522-2586(200007)12:13.0.co;2-v.

  PMID: 10931560 BACKGROUND

• Schnabel RB, Yin X, Gona P, Larson MG, Beiser AS, McManus DD, Newton-Cheh C, Lubitz SA, Magnani JW, Ellinor PT, Seshadri S, Wolf PA, Vasan RS, Benjamin EJ, Levy D. 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study. Lancet. 2015 Jul 11;386(9989):154-62. doi: 10.1016/S0140-6736(14)61774-8. Epub 2015 May 7.

  PMID: 25960110 BACKGROUND

• Shivkumar K, Ellenbogen KA, Hummel JD, Miller JM, Steinberg JS. Acute termination of human atrial fibrillation by identification and catheter ablation of localized rotors and sources: first multicenter experience of focal impulse and rotor modulation (FIRM) ablation. J Cardiovasc Electrophysiol. 2012 Dec;23(12):1277-85. doi: 10.1111/jce.12000. Epub 2012 Nov 6.

  PMID: 23130890 BACKGROUND

• Spertus J, Dorian P, Bubien R, Lewis S, Godejohn D, Reynolds MR, Lakkireddy DR, Wimmer AP, Bhandari A, Burk C. Development and validation of the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) Questionnaire in patients with atrial fibrillation. Circ Arrhythm Electrophysiol. 2011 Feb;4(1):15-25. doi: 10.1161/CIRCEP.110.958033. Epub 2010 Dec 15.

  PMID: 21160035 BACKGROUND

• Wilber DJ. Fibroblasts, focal triggers, and persistent atrial fibrillation: is there a connection? Circ Arrhythm Electrophysiol. 2012 Apr;5(2):249-51. doi: 10.1161/CIRCEP.111.968750. No abstract available.

  PMID: 22511658 BACKGROUND

• Zareian M, Ciuffo L, Habibi M, Opdahl A, Chamera EH, Wu CO, Bluemke DA, Lima JA, Venkatesh BA. Left atrial structure and functional quantitation using cardiovascular magnetic resonance and multimodality tissue tracking: validation and reproducibility assessment. J Cardiovasc Magn Reson. 2015 Jul 1;17(1):52. doi: 10.1186/s12968-015-0152-y.

  PMID: 26126732 BACKGROUND

MeSH Terms

Conditions

Atrial Fibrillation

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Tarek Zghaib
• Organization: Johns Hopkins University

tzghaib1@jhmi.edu

410-955-5000

Study Officials

• Saman Nazarian, MD, PhD

  Hospital of the University of Pennsylvania; Johns Hopkins Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2016
• First Posted: September 29, 2016
• Study Start: April 1, 2016
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: January 4, 2018
• Results First Posted: January 4, 2018

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)