Renal Denervation to Treat Heart Failure With Preserved Ejection Fraction

University of Leipzig68 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Heart Failure With Preserved Ejection Fraction Hypertension, Renal

Interventions

Renal DenervationPROCEDURE

Renal denervation in patients with HFpEF and uncontrolled hypertension

ShamPROCEDURE

Sham Treatment. After six months, cross-over is planned in all sham-treated patients and this patients will also receive a renal denervation.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (5)

Universitätsklinikum Halle (Saale), Klinik und Poliklinik für Innere Medizin III

Halle, Saxony-Anhalt, Germany

RECRUITING

BG Klinikum Unfallkrankenhaus Berlin gGmbH

Berlin, Germany

RECRUITING

Universitätsklinikum Leipzig, Klinik und Poliklinik für Kardiologie

Leipzig, Germany

Outcomes

Primary Outcomes

exercise pulmonary capillary wedge pressure (PCWP) at 20 W workload

To assess the hemodynamic effects of RDN in patients with HFpEF in comparison to sham-treatment

Time frame: 6 months after randomization

Secondary Outcomes

number of combination of death, increase in diuretic therapy, hospitalization for heart failure, worsening NYHA-class, change in pulmonary pressure parameters

number of combined endpoint in RDN and SHAM patients

Time frame: 6, 12 and 24 months after RDN

Change in mean Pulmonary artery (PA) pressure, estimated pulmonary artery diastolic pressure (ePAD) and PA pressure variability from pulmonary pressure sensor measurements

difference between RDN and sham

Time frame: 6 months after randomization

Change in mean PA pressure, ePAD and PA pressure variability from pulmonary pressure sensor measurements

Change in mean PA pressure, ePAD and PA pressure variability from pulmonary pressure sensor measurements, compared to baseline values

Time frame: 6, 12 and 24 months after RDN

Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability

difference between RDN and sham

Time frame: 6 months after randomization

Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability

Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability, compared to baseline values

Time frame: 6, 12 and 24 months after RDN

Difference in ventriculo-arterial coupling

Central Contacts

Karl Fengler, PhD

CONTACT

49 341 Karl.Fengler@medizin.uni-leipzig.de

Philipp Lurz, Prof. Dr.

CONTACT

49 6131 lurzphil@uni-mainz.de

Data from ClinicalTrials.gov

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