APAF: Assessment of Cardiac Resynchronization Therapy in Patients With Permanent Atrial Fibrillation

NCT ID: NCT00111527

Last Updated: 2025-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 458 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2010-03-31

Brief Summary

A suboptimal level of resynchronization (cardiac resynchronization therapy [CRT]) achieved in many patients with actual standards and techniques based on tissue-Doppler echocardiography could be more effective to obtain better CRT results. Eligible patients who successfully received atrioventricular (AV) junction ablation and biventricular (BiV) pacing are randomised to a comparison between a strategy of right ventricular (RV) apical pacing with delayed CRT based on clinical indications with a strategy of early optimal CRT based on an echocardiographic stratification.

End-points:

• Acute echo comparison (acute echo study)
• Quality of life and exercise tolerance (Short-term clinical study)
• Composite end-point of CRT clinical failure (Long-term clinical study)

Detailed Description

Background: Cardiac resynchronization therapy (CRT) in patients in atrial fibrillation (AF) seems to provide modest favorable effect compared with RV pacing. In the Optimal Pacing SITE (OPSITE) trial the results were heterogeneous. The situation was almost certainly one in which some patients are showing marked clinical benefit with LV-based pacing, balanced by other patients in whom RV was the best choice. Therefore with the actual standards, CRT pacing cannot be recommended as a first line treatment for all patients with AF and refractory heart failure and new criteria to identify the patients who might benefit are needed. Furthermore, a pre-requisite for CRT in patients with AF is the presence of stable 3rd degree AV block which usually implies the need for performing catheter ablation of the AV junction.

Study hypothesis: We hypothesized that a suboptimal level of resynchronization is achieved in many patients with actual standards and that some techniques based on tissue-Doppler echocardiography could be more effective to obtain better (hopefully optimal) CRT results.

Objective: The aim of the APAF+ heart failure (HF) trial is to compare, in patients affected by permanent AF and refractory heart failure, a strategy of delayed CRT based on clinical indications with a strategy of early optimal CRT based on an echocardiographic stratification.

Study protocol: Eligible patients who successfully received AV junction ablation and biventricular pacing are randomised to a comparison between a strategy of RV apical pacing with delayed CRT based on clinical indications with a strategy of early optimal CRT based on an echocardiographic stratification. The optimal CRT is defined as the shortest intra-LV delay obtained with tissue-doppler echocardiography among RV, LV and BiV optimised VV interval.

An acute echocardiographic evaluation is performed shortly after randomisation. A short-term clinical evaluation is performed after 6 months. A long-term clinical evaluation is performed up to 24 months.

End-points:

• Acute echo comparison (acute echo study)
• Quality of life and exercise tolerance (Short-term clinical study)
• Composite end-point of CRT clinical failure (Long-term clinical study)

Study size: The study will randomise 458 patients and will be conducted in 46 centres with an average of 10 patients per centre. Patient enrolment time is anticipated to last 2 years. As the study will continue for a period of 12 months after the enrolment of the last patient, total study duration will be approximately 3 years.

Conditions

Congestive Heart Failure; Atrial Fibrillation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

Normal RV pacing

Group Type: ACTIVE_COMPARATOR

normal RV pacing

Intervention Type: OTHER

PM or ICD implant according to patient indication

2

Echo-guided optimization of pacing

Group Type: EXPERIMENTAL

Optimized echo-guided CRT pacing

Intervention Type: OTHER

Echo-TDI guided VV-delay optimization

Interventions

Optimized echo-guided CRT pacing

Echo-TDI guided VV-delay optimization

Intervention Type: OTHER

normal RV pacing

PM or ICD implant according to patient indication

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients with permanent AF in whom a clinical decision had been made to undertake complete AV junction ablation and ventricular pacing because of drug-refractory, severely symptomatic, uncontrolled high ventricular rate
• Patients with permanent AF, drug-refractory heart failure, depressed LV function in whom a clinical decision had been made to undertake left ventricular synchronization pacing

Exclusion Criteria

• New York Heart Association class IV heart failure, or systolic blood pressure ≥80 mmHg
• Severe concomitant non cardiac disease
• Need for surgical intervention
• Myocardial infarction within 3 months
• Primary hypertrophic cardiomyopathy
• Arrhythmogenic right ventricular dysplasia
• Primary valvular heart disease
• Sustained ventricular tachycardia or ventricular fibrillation
• Previously implanted pacemaker
• Inability to obtain reliable RV and LV pacing and persistent AV block

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medtronic

INDUSTRY

Sponsor Role: collaborator

Azienda USL Reggio Emilia - IRCCS

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michele Brignole, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedali del Tigullio, Lavagna, Italy

Carlo Menozzi, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedale S Maria Nuova, Reggio Emilia, Italy

Locations

Michele Brignole

Lavagna, Genova, Italy

Arcispedale S Maria Nuova

Reggio Emilia, Reggio Emilia, Italy

Countries

Italy

References

Brignole M, Gammage M, Puggioni E, Alboni P, Raviele A, Sutton R, Vardas P, Bongiorni MG, Bergfeldt L, Menozzi C, Musso G; Optimal Pacing SITE (OPSITE) Study Investigators. Comparative assessment of right, left, and biventricular pacing in patients with permanent atrial fibrillation. Eur Heart J. 2005 Apr;26(7):712-22. doi: 10.1093/eurheartj/ehi069. Epub 2004 Dec 20.

Reference Type: BACKGROUND

PMID: 15618036 (View on PubMed)

Wood MA, Brown-Mahoney C, Kay GN, Ellenbogen KA. Clinical outcomes after ablation and pacing therapy for atrial fibrillation : a meta-analysis. Circulation. 2000 Mar 14;101(10):1138-44. doi: 10.1161/01.cir.101.10.1138.

Reference Type: BACKGROUND

PMID: 10715260 (View on PubMed)

Auricchio A, Abraham WT. Cardiac resynchronization therapy: current state of the art: cost versus benefit. Circulation. 2004 Jan 27;109(3):300-7. doi: 10.1161/01.CIR.0000115583.20268.E1. No abstract available.

Reference Type: BACKGROUND

PMID: 14744954 (View on PubMed)

Brignole M, Botto G, Mont L, Iacopino S, De Marchi G, Oddone D, Luzi M, Tolosana JM, Navazio A, Menozzi C. Cardiac resynchronization therapy in patients undergoing atrioventricular junction ablation for permanent atrial fibrillation: a randomized trial. Eur Heart J. 2011 Oct;32(19):2420-9. doi: 10.1093/eurheartj/ehr162. Epub 2011 May 23.

Reference Type: DERIVED

PMID: 21606084 (View on PubMed)

Other Identifiers

1893A

Identifier Type: -

Identifier Source: org_study_id