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.
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)