Heart Failure With Preserved Ejection Fraction, Hypertension, Renal
Conditions
Keywords
Renal Denervation, Hypertension, Heart Failure with Preserved Ejection Fraction
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.
Interventions
PROCEDURERenal Denervation
Renal denervation in patients with HFpEF and uncontrolled hypertension
PROCEDURESham
Sham Treatment. After six months, cross-over is planned in all sham-treated patients and this patients will also receive a renal denervation.
Sponsors
ReCor Medical, Inc.
University of Leipzig
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Difference in peak PCWP | 6 months after randomization | Difference in peak PCWP (difference between RDN and sham) as compared to baseline values |
| 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 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 months after randomization | difference between RDN and sham |
| 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 |
| 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 |
| 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 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 NT-proBNP | 6 months after randomization | Difference in NT-proBNP (difference between RDN and sham) as compared to baseline |
| difference in All-cause Mortality | 6 months after randomization | All-cause Mortality (difference between RDN and sham) |
| 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) |
| difference in Frequency of patients with controlled hypertension | 6 months after randomization | Frequency of patients with controlled hypertension (blood pressure within treatment goals in ABPM as recommended by the European Society of Cardiology) (difference between RDN and sham) |
| Difference in 6-minute walk distance | 6 months after randomization | Difference in 6-minute walk distance (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) |
| 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 |
| 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) |
Countries
Germany
Contacts
Primary ContactKarl Fengler, PhD
Backup ContactPhilipp Lurz, Prof. Dr.
Outcome results
None listed