Clinical trial NCT01990911: Renal Sympathetic Denervation Prevents Atrial Fibrillation in Patients With Hypertensive Heart Disease: a Pilot Study
Official title: Renal Sympathetic Denervation Restores Autonomic Imbalance and Prevents Atrial Fibrillation in Patients With Hypertensive Heart Disease: a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Hypertensive Heart Disease
Atrial Fibrillation
Autonomic Imbalance
Keywords: hypertension
hypertensive heart disease
atrial fibrillation
autonomic imbalance
Lead sponsor: Pace Clinic
Sponsor class: OTHER
Collaborators: name: University Hospital, Saarland
First posted: 2013-11-25
Enrollment: 80
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The autonomic nervous system plays an important role in the precipitation of AF in structurally-abnormal hearts. Restoration of autonomic imbalance may therefore prevent new-onset AF.

Renal artery denervation (RDN) is a novel percutaneous procedure that uses radio-frequency energy to destroy the sympathetic renal nerves. Symplicity 1 and -2 studies have shown that RDN effectively reduces blood pressure in up to 80% of treated patients. LVH regression and improvement of diastolic dysfunction follow as a consequence of afterload reduction and renin-angiotensin-aldosterone system modulation. RDN may thus also reduce intra-atrial pressure resulting in less stretch of the pulmonary venous ostia where most ectopic AF-foci originate.

Hypothesis: RDN restores autonomic imbalance in HTHD and lowers intra-atrial pressure by reducing afterload. These synergistic mechanisms may prevent new-onset AF.

Detailed description: One hundred consenting patients meeting all inclusion criteria will undergo an exercise stress test, 2D and M-Mode echocardiograms and 24-hour ambulatory blood pressure holter monitoring prior to being randomised to receive either renal denervation (RDN) with a Symplicity renal denervation catheter plus medical therapy or medical therapy alone. Coronary angiography with/without coronary revascularisation will be performed as per the treating cardiologist's clinical judgement and a Reveal® holter will be implanted in all patients at the end of the procedure.

Time zero will be defined as starting at three months after the procedure. Follow up visits will be scheduled to scan the holter for the primary end point, i.e. high atrial rates (AF-surrogate defined as: "episodes of atrial rate \>190 beats per minute for more than 6 minutes") or new-onset AF. Patients will be followed six monthly for three years.

Eligibility criteria: Inclusion Criteria:

* Must have an indication for coronary angiography e.g.
* Acute coronary syndrome
* Positive stress ECG: - Defined as ≥1mm ST segment shift (depression or elevation) in ≥2 contiguous leads with/without chest discomfort)
* Age ≥55 years
* Office blood pressure ≥160/90mmHg in non-diabetics or ≥150/90mmHg in diabetics
* Subjects must be on at least 3 anti-hypertensive drugs, including a diuretic agent
* Sinus rhythm
* Left ventricular hypertrophy defined on echo as:
* Estimated LV mass \> 255 g or LVMI \>131 g/m2 for men
* Estimated LV mass \>193 g or LVMI \>113 g/m2for women
* Left atrial diameter ≥45mm on any echocardiographic window

Exclusion Criteria:

* Estimated glomerular filtration rate (eGFR) \< 45ml/min/1.73m2
* Renal artery anatomy unsuitable for RDN
* Substantial stenotic valvular heart disease
* Pregnancy or planned pregnancy
* Thyrotoxicosis
* Patients needing to undergo coronary artery bypass surgery

Primary outcomes:
measure: Atrial fibrillation
timeFrame: 3 years
Secondary outcomes:
measure: Restoration of autonomic imbalance
timeFrame: 3 years
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: Pace Clinic
state: Western Cape
Study officials:
affiliation: Tygerberg Hospital and Stellenbosch University
name: Paul A Brink, PhD
role: STUDY_DIRECTOR
affiliation: University Hospital, Saarland
name: Michael Bohm, PhD
role: STUDY_DIRECTOR
References:
citation: Heradien M, Mahfoud F, Greyling C, Lauder L, van der Bijl P, Hettrick DA, Stilwaney W, Sibeko S, Jansen van Rensburg R, Peterson D, Khwinani B, Goosen A, Saaiman JA, Ukena C, Bohm M, Brink PA. Renal denervation prevents subclinical atrial fibrillation in patients with hypertensive heart disease: Randomized, sham-controlled trial. Heart Rhythm. 2022 Nov;19(11):1765-1773. doi: 10.1016/j.hrthm.2022.06.031. Epub 2022 Jun 30.