Effect of Renal Denervation on Atrial Fibrillation

Study Overview
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Brief Summary
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The purpose of the ERDAF study (Effect of Renal Denervation on Atrial Fibrillation) is to evaluate the renal sympathetic denervation in patients with resistant arterial hypertension and symptomatic paroxysmal or persistent atrial fibrillation(AF) in order to show if there is a reduction in the AF-related symptoms, the AF recurrence rate, and the total burden (symptomatic and/or asymptomatic) of the arrhythmia. To the best of our knowledge, ERDAF is the first randomized study, which is going to evaluate the effect of RDN [without pulmonary vein isolation (PVI)] on AF recurrence profile and AF ''burden'' using continuous long-term rhythm monitoring via ILRs for a period of 18 months. Hypothesis Renal sympathetic denervation in patients with resistant hypertension and symptomatic paroxysmal or persistent atrial fibrillation reduces AF recurrences, total AF burden (asymptomatic / symptomatic) and limits the AF-related symptoms.

Detailed Description
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In arterial hypertension (AH), a significant proportion of patients, despite the optimal medical therapy, do not achieve adequate blood pressure (BP) control (resistant hypertension). Renal sympathetic denervation (RDN) is a novel alternative minimally invasive therapeutic option for patients with resistant AH. Recent data has shown that RDN with or without pulmonary vein isolation (PVI) may also have a positive impact on the management of patients with paroxysmal or persistent atrial fibrillation (AF). However, there is no randomized study, to date, suggesting that RDN itself (without PVI) reduces the AF recurrences, symptoms, and the total burden of the arrhythmia. The purpose of this study [Effect of Renal Denervation on Atrial Fibrillation (ERDAF)] is to evaluate the RDN (without PVI) in patients with resistant AH and symptomatic paroxysmal or persistent AF in order to show if there is benefit in the incidence of AF recurrences, the total AF burden (symptomatic and asymptomatic) as well as the BP control. This is a single-center, randomized study in which thirty (30) patients with resistant AH and symptomatic paroxysmal or persistent AF will be randomized (1:1) after sinus rhythm restoration and implantation of an implantable loop recorder (ILR), in either RDN (n=15) or conventional treatment of resistant AH with optimal drug therapy (n=15). Patients will be followed-up every three months and for a period of 18 months after the implantation of the ILR. The first three months after RDN will be excluded from our final analysis (blanking period). The primary endpoint will be the change in the total AF burden (Total time in AF during the follow-up period). Secondary endpoints will include the change in the symptomatic and asymptomatic burden of AF, the time to detect the first AF recurrence (symptomatic and/or asymptomatic)-early recurrence of AF after RDN, and the change in BP during the follow-up period.

Official Title
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Effect of Renal Denervation on Atrial Fibrillation

Conditions
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Arterial Hypertension, Atrial Fibrillation

Intervention / Treatment
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* Procedure: Sympathetic Renal Denervation
* Device: Implantable Loop Recorder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients >18 years with resistant hypertension [Systolic Blood Pressure (SBP) ≥ 140 mmHg and/or Diastolic Blood Pressure (DBP) ≥ 90 mmHg despite treatment with ≥ 3 antihypertensive drugs of various classes, including a diuretic) and symptomatic paroxysmal or persistent AF will be included in the study after sinus rhythm restoration Exclusion Criteria: Patients with permanent AF or patients with long-standing persistent AF as defined by the current ESC guidelines for the management of AF1. Patients with a glomerular filtration rate (eGFR)] <45 ml / min / 1.73 m2 calculated using the CKD-EPI43. Patients with secondary arterial hypertension. Patients with an established diagnosis of resistant hypertension <6 months. Patients with severe renal artery stenosis or previous renal artery angioplasty. Patients who have undergone or are about to undergo pulmonary vein isolation. Patients with left end-diastolic ventricle diameter >60 mm in men or >55mm in women. Patients with a left ventricular ejection fraction <35% in the transthoracic echocardiogram (TTE). Patients with AF possible reversible causes (pulmonary embolism, acute coronary syndromes, thyrotoxicosis, alcohol abuse, etc.) Patients with heart failure in NYHA III-IV stage. Patients with life expectancy <1 year. Pregnant women. Patients who are unable to give consent to participate in the study. Patients who do not wish to give written consent to participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sympathetic Renal Denervation<br>Sympathetic Renal Denervation | Procedure: Sympathetic Renal Denervation<br>* Catheter-based sympathetic renal denervation (RDN) using radiofrequency, ultrasound, or perivascular injection of neurotoxic agents such as alcohol has been introduced as a minimally invasive alternative treatment option for patients with resistant hypertension. RDN consists of endovascular catalysis of the kidney sympathetic nerves running in the wall of the renal arteries.<br>Device: Implantable Loop Recorder<br>* Implantable Loop Recorders (ILRs) are small, subcutaneously implanted devices that are able to detect and store atrial fibrillation episodes lasting longer than 2 minutes with high sensitivity (96.1-100%) and good specificity (67-85.4%) for a period of up to three years.<br>* Other names: Insertable Cardiac Monitor;|
| Active Comparator: Conventional treatment with drug therapy<br>Conventional drug therapy of resistant hypertension | Device: Implantable Loop Recorder<br>* Implantable Loop Recorders (ILRs) are small, subcutaneously implanted devices that are able to detect and store atrial fibrillation episodes lasting longer than 2 minutes with high sensitivity (96.1-100%) and good specificity (67-85.4%) for a period of up to three years.<br>* Other names: Insertable Cardiac Monitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in the total AF burden (symptomatic and asymptomatic AF burden) during the follow-up period. | AF burden: The amount of time (minutes or hours) the patient is in AF out of the total follow-up period. | From 3 months to 18 months.The first three months after RDN will be excluded from our final analysis (blanking period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the symptomatic AF burden during the follow-up period. | Symptomatic AF ''burden'': The amount of time (minutes or hours) in which the patient is in AF, perceived by the patient AF, out of the total follow-up period. | From 3 months to 18 month.The first three months after RDN will be excluded from our final analysis (blanking period) | 
| Change in asymptomatic AF burden during the follow-up period. | Asymptomatic AF burden: The amount of time (minutes or hours) in which the patient is in AF that the patient does not perceive out of the total follow-up period. | From 3 months to 18 months. The first three months after RDN will be excluded from our final analysis (blanking period) | 
| The time interval for the detection of the first AF recurrence after the ILR implantation during the follow-up period. |  | From 3 months to 18 months. The first three months after RDN will be excluded from our final analysis (blanking period) | 
| The time interval for detection of the first symptomatic recurrence of the arrhythmia after the ILR implantation during the follow-up period. |  | From 3 months to 18 months. The first three months after RDN will be excluded from our final analysis (blanking period) | 
| Change in blood pressure (systolic, diastolic, and mean blood pressure) as measured by 24-hour ambulatory blood pressure monitoring (ABPM) during the follow-up period. |  | From 3 months to 18 months. The first three months after RDN will be excluded from our final analysis (blanking period) | 
| Change in office blood pressure (systolic, diastolic). |  | From 3 months to 18 months. The first three months after RDN will be excluded from our final analysis (blanking period) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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arterial hypertension, atrial fibrillation, renal denervation, autonomous nervous system, implantable loop recorder, continuous monitoring, burden, insertable cardiac monitor, resistant hypertension