Renal Denervation to Treat Heart Failure With Preserved Ejection Fraction - A Pilot Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 68
- 试验地点
- 10
- 主要终点
- exercise pulmonary capillary wedge pressure (PCWP) at 20 W workload
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
- •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%)
- •NYHA-Class II or III
- •Confirmation of an elevated cardiac filling pressures (either LVEDP >= 16 mmHg or PCWP >= 15 mmHg at rest or >=25 mmHg during exercise) by catheterization
- •Age 18-80 years
- •Written informed consent
排除标准
- •≥1 main renal artery diameter <3.0 mm
- •main renal artery length < 20 mm
- •a single functioning kidney
- •presence of abnormal kidney tumors
- •renal artery aneurysm
- •pre-existing renal stent or history of renal artery angioplasty
- •fibromuscular disease of the renal arteries
- •presence of renal artery stenosis of any origin ≥50%
- •iliac/femoral artery stenosis precluding femoral access for RDN
- •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).
- •participation in other interventional trials
- •patients under legal supervision or guardianship
- •suspected lack of compliance
- •pregnant women
- •Presence of intracardiac pacemakers or implantable cardioverter/defibrillators
结局指标
主要结局
exercise pulmonary capillary wedge pressure (PCWP) at 20 W workload
时间窗: 6 months after randomization
To assess the hemodynamic effects of RDN in patients with HFpEF in comparison to sham-treatment
次要结局
- Difference in ventriculo-arterial coupling(6 months after randomization)
- Difference in resting and exercise PCWP (at 20, 40, 60, 80 W, and maximum workload)(6 months after randomization)
- difference in Frequency of patients with controlled hypertension(6, 12 and 24 months after RDN)
- Change in Minnesota living with heart failure questionnaire(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(6 months after randomization)
- Change in mean PA pressure, ePAD and PA pressure variability from pulmonary pressure sensor measurements(6, 12 and 24 months after RDN)
- Change in Systolic/Diastolic 24h blood pressure by ABPM and blood pressure variability(6, 12 and 24 months after RDN)
- difference in cardiac mortality(6 months after randomization)
- difference in major adverse cardiovascular events(6 months after randomization)
- difference in number of Adverse Events(6 months after randomization)
- Change in Cardiac magnetic resonance (CMR) based hemodynamics(6 months after randomization)
- Difference in peak PCWP(6 months after randomization)
- Difference in 6-minute walk distance(6, 12 and 24 months after RDN)
- 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)
- Change in ventriculo-arterial coupling(6 months after randomization)
- Difference in NT-proBNP(6, 12 and 24 months after RDN)
- difference in All-cause Mortality(6 months after randomization)
- Change in exercise BP and maximum maximum exercise capacity(6 months after randomization)
- Change in Minnesota living with heart failure questionnaire (difference between RDN and sham)(6 months after randomization)
- number of patients with Hospitalizations for heart failure(6 months after randomization)
研究者
Karl Fengler
PhD
University of Leipzig