Atrioventricular Node Ablation and Conduction System Pacing in Patients with Well Controlled Permanent Atrial Fibrillation (AF), Heart Failure and Preserved Ejection Fraction: Heart Rate Regularization Versus Medical Rate Control

The goal of this clinical trial is to assess the clinical efficacy of physiological pacing combined with atrioventricular node ablation, in patients with Heart Failure with preserved Ejection Fraction (HFpEF) and well controlled permanent atrial fibrillation.The main question it aims to answer is that heart rate regularization added to physiological pacing - preventing the deleterious effect of right ventricular apical pacing - would reduce mortality and heart failure hospitalizations.

Researchers will compare physiological pacing combined with atrioventricular node ablation (intervention arm) versus optimal pharmacological therapy (control arm) to see if physiological pacing combined with atrioventricular node ablation reduce time to the composite of all-cause mortality or hospitalization due to heart failure or intravenous diuretics (time frame 24 months).

Participants will :

* Be randomized in intervention arm or control arm.
* Visit the clinic 3 months, 12 months and 24 months after the randomization for checkups and tests.

Heart failure with preserved ejection fraction is a major public health issue affecting 4.9% of general population aged ≥ 60 years. It accounts for more than half of all heart failure hospital admissions. Atrial fibrillation is very common in this diseased population as pathophysiologies are highly interrelated. Atrial fibrillation occurs in two thirds of Heart failure with preserved ejection patients at some point in the natural history and confers a poor prognosis. Therapeutic alternatives are currently limited as patients with permanent Atrial fibrillation and Heart failure with preserved ejection are often treated with drug therapies for lenient rate control.

Recently, the APAF-CRT mortality trial demonstrated a reduction in mortality and hospitalization in Heart Failure and Atrial fibrillation patients treated with Atrioventricular node ablation plus Cardiac Resynchronization Therapy versus pharmacological rate control, irrespective of their baseline Ejection Fraction. The optimal rate regularization achieved with atrioventricular node ablation emerges as the main determinant of reduction in mortality and hospitalization. This conclusion is supported by old robust physiology studies showing that beat-to-beat heart rate irregularity has significant hemodynamic effects and notably decreases cardiac output. However, no specific trials have been conducted in patients with Heart failure with preserved ejection, a population for whom treatment strategies that effectively improve outcomes are sparse. We aim at analyzing the benefit of heart rate regularization and physiological pacing in patients with Heart failure with preserved ejection (Left Ventricular Ejection Fraction ≥ 50%) and permanent Atrial Fibrilation.

We hypothesize that heart rate regularization added to physiological pacing - preventing the deleterious effect of right ventricular apical pacing - would reduce mortality and Heart Failure hospitalizations.

Eligibility Criteria:
Inclusion Criteria:

* Permanent atrial fibrilation \> 6 months
* Preserved Left Ventricular Ejection Fraction ≥ 50%
* ≥ 1 heart failure hospitalization in the previous year
* NYHA (New York Heart Association) score ≥ 2
* Presence of at least one of the following criteria related to diastolic dysfunction:

  * E/e' ratio \> 9
  * Left Ventricular mass \> 95 g/m2 (female) or \> 115 g/m2 (male) with h/R ratio \> 0.42
  * NT pro BNP (B-type Natriuretic Peptide) \> 365 pg/mL or BNP (B-type Natriuretic Peptide) \> 105 pg/mL
* Narrow QRS ≤ 120 ms
* Average heart rate ≤ 110/min on 24 hours Holter monitoring
* Age over 18-year-old
* Capacity to understand the nature of the study, legal ability and willingness to give informed consent
* Patient covered by a social insurance
* Effective contraception and a negative pregnancy test in women of a childbearing age

Exclusion Criteria:

* Patient eligible for atrial fibrilation catheter ablation
* Life expectancy \< 12 months
* Severe chronic kidney disease (estimated Glomerular Filtration Rate ≤ 20 ml/1,73 m2)
* Severe respiratory disease (severe chronic obstructive pulmonary disease with Gold ≥ 3 and/or chronic oxygen therapy)
* Class III obesity (Body Mass Index ≥ 40)
* Confirmed or suspected infiltrative cardiomyopathy (amyloidosis, sarcoidosis, Fabry disease, others)
* Obstructive hypertrophic cardiomyopathy
* Previous implanted devices (Pacemaker / Implantable Cardioverter-Defibrillator / Cardiac Resynchronization Therapy)
* Other indication for pacemaker implantation
* Indication for implantable cardioverter-defibrillator
* Ambulatory ≤ 50% of time
* Pregnant women
* Breast-feeding women