Renal Denervation to Treat Heart Failure With Preserved Ejection Fraction

Not Applicable

Recruiting

• Conditions: Hypertension, Renal; Heart Failure With Preserved Ejection Fraction
• Interventions: Procedure: Sham; Procedure: Renal Denervation

• Registration Number: NCT05030987
• Lead Sponsor: University of Leipzig

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2021-08-30
• Study First Submitted QC: 2021-08-30
• Study First Posted: 2021-09-01
• Study Start: 2021-11-30
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-15
• Last Update Posted: 2024-07-17
• Primary Completion: 2024-12-31
• Study Completion: 2026-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 68

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham	Sham	Sham Procedure
RDN	Renal Denervation	Renal Denervation

Primary Outcome Measures

Name	Time	Method
exercise pulmonary capillary wedge pressure (PCWP) at 20 W workload	6 months after randomization	To assess the hemodynamic effects of RDN in patients with HFpEF in comparison to sham-treatment

Secondary Outcome Measures

Name	Time	Method
Difference in ventriculo-arterial coupling	6 months after randomization	Difference in ventriculo-arterial coupling (by end-systolic elastance and arterial elastance) as acquired by invasive measurement
Difference in resting and exercise PCWP (at 20, 40, 60, 80 W, and maximum workload)	6 months after randomization	Difference in resting and exercise PCWP (at 20, 40, 60, 80 W, and maximum workload) (difference between RDN and sham) as compared to baseline values
difference in Frequency of patients with controlled hypertension	6, 12 and 24 months after RDN	Frequency of patients with controlled hypertension (blood pressure within treatment goals in ABPM as recommended by the European Society of Cardiology) as compared to baseline
Change in Minnesota living with heart failure questionnaire	6, 12 and 24 months after RDN	Change in Minnesota living with heart failure questionnaire, compared to baseline
Change in mean Pulmonary artery (PA) pressure, estimated pulmonary artery diastolic pressure (ePAD) and PA pressure variability from pulmonary pressure sensor measurements	6 months after randomization	difference between RDN and sham
Change in mean PA pressure, ePAD and PA pressure variability from pulmonary pressure sensor measurements	6, 12 and 24 months after RDN	Change in mean PA pressure, ePAD and PA pressure variability from pulmonary pressure sensor measurements, compared to baseline values
Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability	6, 12 and 24 months after RDN	Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability, compared to baseline values
difference in cardiac mortality	6 months after randomization	cardiac mortality (difference between RDN and sham)
difference in major adverse cardiovascular events	6 months after randomization	major adverse cardiovascular events (composite of cardiac death, myocardial infarction, stroke and hospitalization for heart failure) (difference between RDN and sham)
difference in number of Adverse Events	6 months after randomization	Adverse events (difference between RDN and sham)
Change in Cardiac magnetic resonance (CMR) based hemodynamics	6 months after randomization	Change in CMR-based hemodynamics (difference between RDN and sham) as compared to baseline values
Difference in peak PCWP	6 months after randomization	Difference in peak PCWP (difference between RDN and sham) as compared to baseline values
Difference in 6-minute walk distance	6, 12 and 24 months after RDN	Difference in 6-minute walk distance as compared to baseline
number of combination of death, increase in diuretic therapy, hospitalization for heart failure, worsening NYHA-class, change in pulmonary pressure parameters	6, 12 and 24 months after RDN	number of combined endpoint in RDN and SHAM patients
Change in ventriculo-arterial coupling	6 months after randomization	Change in ventriculo-arterial coupling (cMRI and echocardiogram) (difference between RDN and sham) as compared to baseline values
Difference in NT-proBNP	6, 12 and 24 months after RDN	Difference in NT-proBNP as compared to baseline
difference in All-cause Mortality	6 months after randomization	All-cause Mortality (difference between RDN and sham)
Change in exercise BP and maximum maximum exercise capacity	6 months after randomization	Change in exercise BP between baseline and 6 months and maximum exercise capacity between baseline and 6 months (difference between RDN and sham)
Change in Minnesota living with heart failure questionnaire (difference between RDN and sham)	6 months after randomization	Change in Minnesota living with heart failure questionnaire (difference between RDN and sham)
number of patients with Hospitalizations for heart failure	6 months after randomization	number of patients with Hospitalizations for heart failure (difference between RDN and sham)

Trial Locations

Locations (5)

Universitätsklinikum Leipzig, Klinik und Poliklinik für Kardiologie; 🇩🇪 Leipzig, Germany

BG Klinikum Unfallkrankenhaus Berlin gGmbH; 🇩🇪 Berlin, Germany

Universitätsmedizin der Johannes Gutenberg Universität Mainz, Zentrum für Kardiologie / Kardiologie 1; 🇩🇪 Mainz, Germany

Universitätsklinikum Halle (Saale), Klinik und Poliklinik für Innere Medizin III; 🇩🇪 Halle, Sachsen Anhalt, Germany

Herzzentrum Leipzig, Universitätsklinik für Kardiologie; 🇩🇪 Leipzig, Germany