Rationale: Perirenal adipose tissue (PRAT) thickness has been associated to worsening renal function and hypertension. The role of PRAT in heart failure with a preserved ejection fraction (HFpEF) has never been established. The hypothesis of this study is that in patients with HFpEF the diameter of PRAT is increased compared with age, sex and BMI matched controls.

Objective: The main objective is to determine whether PRAT thickness is increased in patients with HFpEF. Secondary objectives are to determine whether PRAT thickness is correlated to whole kidney perfusion, renal venous flow patterns, markers of glomerular and tubular damage and dysfunction, NT pro-BNP, renin and aldosterone. Lastly, this study aims to determine whether these correlations are similar for men and women with HFpEF.

Study design: the proposed study is a single center, cross-sectional observational case-control study, including 30 HFpEF patients and 30 healthy controls.

Study population: Adult patients with HFpEF with a body mass index (BMI) of <25.0 or >30.0 and healthy age, sex and BMI-matched controls.

Intervention (if applicable): Not applicable. Main study parameters/endpoints: The primary endpoint will be the difference in diameter and volume of perirenal adipose tissue measured on dynamic contrast computed CT (DCE-CT) in patients with HFpEF vs. healthy age, sex and BMI matched controls.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participating subjects will be asked to visit the University Medical Center Groningen (UMCG) twice (once for screening, once for testing visit). During the testing visit they will undergo intravenous contrast abdominal CT, renal sonography, blood drawing and urine collection. Risks associated with these procedure are very limited, rare and include bleeding and infection for venapunction, and contact dermatitis for ultrasound gel. Adverse events for CT include hypersensitivity reactions to contrast agent, which include skin rash, hypotension and bronchospasm.

Inclusion criteria (patient category):

1. Able and willing to give written informed consent

2. Male and female subjects with age >18 years

3. A diagnosis of HFpEF based on typical symptoms (and/or signs), a LVEF >50% (assessed within 12 months prior to baseline testing) and at least two of the following criteria10:

   1. For BMI <35.0 kg/m2: NT pro-BNP ≥220 pg/mL For BMI ≥35.0 kg/m2: NT pro-BNP ≥125 pg/mL
   2. Left atrial volume index >34 ml/m2 or Left ventricular mass index >115g/m2 (men) or >95g/m2 (women)
   3. E/e' ≥13 or e' average <9 cm/s

4. BMI <25 or >30

Exclusion criteria for patient category:

1. Amyloid cardiomyopathy or cardiomyopathy due to sarcoïdosis or M. Fabry, as reflected by medical history.
2. Atrial fibrillation on ECG performed at screening
3. Genetic hypertrophic (obstructive) cardiomyopathy.
4. Severe (grade III/III) aortic stenosis.
5. Female patient with childbearing potential, aiming to get pregnant or pregnant at the time of inclusion.
6. Patients on (intermittent or continuous) hemodialysis
7. Proven hypersensitivity to iodine contrast or any other contra-indication for computed tomography.

Inclusion criteria for healthy controls:

1. Able and willing to give written informed consent
2. Male and female subjects with age >18 years
3. BMI <25 or >30

Exclusion criteria for healthy controls:

1. Diagnosis of any cardiovascular disease, either in the medical history or diagnosed during screening.
2. Diagnosis of diabetes mellitus, defined as use of glucose lowering drugs
3. Diagnosis of hypertension, defined as mean of 3 blood pressures measurements of >140/90 mmHg at screening or use of blood pressure lowering drugs.
4. Female patients with childbearing potential, either already pregnant or aiming to get pregnant at the time of inclusion.
5. Proven hypersensitivity to iodine contrast or any other contra-indication for computed tomography.

Patients with chronic, stable HFpEF with and without obesity will be compared to healthy controls with and without obesity.