Denervation of the renAl sympathetIc nerveS in hearT Failure With nOrmal Lv Ejection Fraction
Denervation of the renAl sympathetIc nerveS in hearT Failure With nOrmal Lv Ejection Fraction
Increasing evidence suggests an important role of activation of the sympathetic nervous
 system (SNS) in the clinical phenomena of heart failure with normal left ventricular ejection
 fraction and hypertension. The current study aims to evaluate efficacy and safety of renal
 sympathetic denervation for the modulation of the SNS in patients with heart failure with
 normal LV ejection fraction.
Rationale: Increasing evidence suggests an important role of activation of the sympathetic
 nervous system (SNS) in the clinical phenomena of heart failure with normal left ventricular
 ejection fraction and hypertension. Moreover, sympathetic activation of the kidneys is
 directly proportional related to the severity of the heart failure state. Therapeutic renal
 denervation (PRDN), the deliberate disruption of the nerves connecting the kidneys with the
 central nervous system, has been shown to be an effective means of modulating elevated SNS
 activity. The current study aims to evaluate efficacy and safety of renal sympathetic
 denervation for the modulation of the SNS in patients with heart failure with normal LV
 ejection fraction.

 Objective: Primary objectives: To investigate the efficacy of PRDN by means of pulsed wave
 Doppler echocardiographic parameters in patients diagnosed with HFNEF and hypertension.
 Secondary objectives: to investigate the safety of PRDN in patients with heart failure with
 normal LV ejection fraction and hypertension and to compare changes in the following
 parameters in patients with HFNEF and hypertension after PRDN: LV mass, LV volume, LA volume,
 LVEF, MIBG-uptake and -washout, BNP levels, blood pressure, heart rate variability, exercise
 capacity and quality of life.

 Study design: Multicentre, prospective, randomised controlled trial. 60 patients will be
 randomly allocated in a one-to-one ratio to undergo renal denervation with previous treatment
 (n=30) or to maintain previous treatment alone (n=30) at 2 participating centres.
 Randomisation will be done with sealed envelopes.

 Study population: Patients diagnosed with heart failure with normal LV ejection fraction and
 treated for hypertension. Patients should have a stable drug regimen, with at least 2
 antihypertensive agents. This drug regimen should be expected to be maintained for at least 6
 months.

 ￼￼￼￼￼￼￼￼￼Endpoints: The efficacy of PRDN will be evaluated primarily using echocardiographic
 parameters. Also, safety of PRDN on major and minor adverse events, LV mass, LV and LA
 dimensions, MIBG uptake and clinical endpoints will be evaluated.
Inclusion Criteria:

 -  Individual is diagnosed with heart failure with a normal LV ejection fraction. The
 diagnosis of HFNEF requires the following conditions to be satisfied:

 -  signs or symptoms of heart failure;

 -  normal or mildly abnormal systolic LV function (LVEF ≥ 50%);

 -  evidence of diastolic LV dysfunction.

 -  Individual should fulfill the diagnostic WHO criteria for hypertension: SBP > 140 mmHg
 and/or DBP > 90 mmHg, and is treated with at least 2 antihypertensive drugs. This
 treatment is expected to be maintained for at least 6 months. Using this regimen the
 blood pressure should be adequately controlled (< 140/90mmHg by 24 hour ambulatory BP
 measurement).

 -  Individual is adhering to a stable drug regimen HFNEF, with no changes for a minimum
 of 2 weeks prior to enrollment, and which is expected to be maintained for at least 6
 months.

 -  Individual is ≥ 18 years of age.

 Exclusion Criteria:

 -  Known secondary cause of hypertension

 -  Anatomy not eligible for renal denervation

 -  Systolic heart failure (LVEF < 50%)

 -  Individual has an estimated glomerular filtration rate (eGFR) of < 30mL/min/1.73m2,
 using the MDRD calculation.

 -  Individual has any serious medical condition, which in the opinion of the
 investigator, may adversely affect the safety and/or effectiveness of the participant
 or the study (i.e., patients with clinically significant peripheral vascular disease,
 abdominal aortic aneurysm, bleeding disorders such as thrombocytopenia, haemophilia,
 significant anaemia, or arrhythmias such as atrial fibrillation).

 -  Individual is pregnant, nursing or planning to be pregnant.