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

Phase 3
Completed
Conditions
Congestive Heart Failure
Atrial Fibrillation
Interventions
Other: normal RV pacing
Other: Optimized echo-guided CRT pacing
Registration Number
NCT00111527
Lead Sponsor
Arcispedale Santa Maria Nuova-IRCCS
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
458
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1normal RV pacingNormal RV pacing
2Optimized echo-guided CRT pacingEcho-guided optimization of pacing
Primary Outcome Measures
NameTimeMethod
Short-term clinical study (6 months): Quality of life (measured as Minnesota Living with Heart Failure Questionnaire, Specific Symptom Scale and New York Heart Association classification) and exercise capacity at 6 months in the 2 study groups6 months
Long-term clinical study (24 months): Composite end-point of: death due to cardiovascular cause, hospitalisation for worsening heart failure, worsening heart failure or failure to achieve a persistent subjective symptom improvement (clinical failure)24 months
Secondary Outcome Measures
NameTimeMethod
The evaluation of the predictive value of echo desynchronisation indexes (inter and intra-LV delays) for identification of clinical failure (see above)24 months
Cost-benefit comparison of the 2 pacing strategies24 months

Trial Locations

Locations (2)

Michele Brignole

🇮🇹

Lavagna, Genova, Italy

Arcispedale S Maria Nuova

🇮🇹

Reggio Emilia, Italy

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