Renal Denervation to Treat Heart Failure With Preserved Ejection Fraction (UNLOAD-HFpEF)

University of Leipzig

Status: Enrolling

Conditions: Hypertension, Renal; Heart Failure With Preserved Ejection Fraction

Treatments: Procedure: Sham; Procedure: Renal Denervation

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05030987

CIV-20-10-034846 (Other Identifier)

UNLOAD-HFpEF

Details and patient eligibility

About

Heart failure with preserved ejection fraction has a high mortality, which is contrasted by a total absence of therapy options besides symptomatic diuretic treatment. This study aims to explore the potential of renal denervation as a treatment option for heart failure with preserved ejection fraction.

Full description

Heart failure is one of the most important diseases worldwide, with a 5-year mortality of up to 75% in symptomatic patients. While substantial progress has been made in the treatment of patients with reduced left ventricular ejection fraction (HFrEF), mortality for patients with heart failure and preserved ejection fraction (HFpEF) remains unchanged, despite a comparable prevalence and mortality of the disease as for heart failure with reduced ejection fraction.

HFpEF is a heterogeneous condition and has been a diagnostic and therapeutic challenge for clinicians and researchers over the past decades. While some rare cases of HFpEF can be attributed to specific diseases like amyloidosis, in most other patients common characteristics are increased ventricular filling pressures and ventricular and arterial stiffening as frequently caused by ageing, diabetes and arterial hypertension. Furthermore, increased sympathetic activity has been described as one pathogenic contributor to chronic heart failure and is associated with poor clinical prognosis. It also leads to a more pulsatile BP profile which can cause a mismatch in arterio-ventricular coupling.

The modulating effects on the sympathetic nervous system induced by renal denervation (RDN) should be beneficial in HFpEF, as they improve resting and exercise hemodynamics due to an improved ventriculoarterial coupling by reduced aortic stiffness and lower systemic blood pressure. In addition, RDN leads to optimized stroke volume and stroke work and might affect cardiac preload by improving blood distribution into the splanchnic compartment.

This study aims to explore the potential of RDN as a therapy for HFpEF in a single center pilot trial using a randomized, sham-controlled double-blind design.

Enrollment: 68 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. confirmed arterial hypertension (1-5 antihypertensive drugs without any dosage change in the preceding 4 weeks) and average systolic BP between >125 and ≤170 mmHg and diastolic BP ≤110 mmHg in 24h ambulatory blood pressure measurement (ABPM)
2. HFpEF (defined by clinical signs and/or symptoms of heart failure, objective structural cardiac abnormalities according to the ESC (European Society of Cardiology) criteria [1], elevated NT-proBNP ≥125 pg/mL and left-ventricular ejection fraction ≥55%)
3. NYHA-Class II or III
4. Confirmation of an elevated cardiac filling pressures (either LVEDP >= 16 mmHg or PCWP >= 15 mmHg at rest or >=25 mmHg during exercise) by catheterization
5. Age 18-80 years
6. Written informed consent

Exclusion criteria

1. ≥1 main renal artery diameter <3.0 mm
2. main renal artery length < 20 mm
3. a single functioning kidney
4. presence of abnormal kidney tumors
5. renal artery aneurysm
6. pre-existing renal stent or history of renal artery angioplasty
7. fibromuscular disease of the renal arteries
8. presence of renal artery stenosis of any origin ≥50%
9. iliac/femoral artery stenosis precluding femoral access for RDN
10. fertile women (within two years of their last menstruation) without appropriate contraceptive measures (implanon, injections, oral contraceptives, intrauterine devices, partner with vasectomy) while participating in the trial (participants using a hormone-based method have to be informed of possible effects of the trial device on contraception).
11. participation in other interventional trials
12. patients under legal supervision or guardianship
13. suspected lack of compliance
14. pregnant women
15. Presence of intracardiac pacemakers or implantable cardioverter/defibrillators

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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68 participants in 2 patient groups

RDN

Experimental group

Description:

Renal Denervation

Treatment:

Procedure: Renal Denervation

Sham

Sham Comparator group

Description:

Sham Procedure

Treatment:

Procedure: Sham