Clinical trial NCT04886713: Adipose Tissue Inflammation in HFpEF
Official title: Adipose Tissue Inflammation in the Development, Maintenance and Functional Impairments in Heart Failure With Preserved Ejection Fraction
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Heart Failure With Preserved Ejection Fraction
Obesity
Lead sponsor: Heart Center Leipzig - University Hospital
Sponsor class: OTHER
First posted: 2021-05-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Stable patients with indication for coronary bypass crafting will be prospectively identified at the Heart Center Leipzig (either during the admission process for patients referred to surgery or at the time of coronary angiography when the indication for operative revascularization is established). Patients will be grouped according to the presence of HFpEF and obesity in order to generate 3 distinct patient groups, defined as:

1. Obesity HFpEF
2. Obesity Non-HF
3. Non-Obesity Non-HF

Brief summary: To evaluate the role of adipose tissue inflammation in patients with heart failure with preserved ejection fraction (HFpEF). Patients undergoing coronary artery bypass grafting with HFpEF and without heart failure will be included in this prospective study. Epicardial, paracardial, paraaortic/paravascular, subcutaneous adipose tissue samples as well as myocardial tissue will be harvested during cardiac surgery. Inflammatory patterns of these tissues and their relation to circulating markers will be investigated.

Detailed description: Heart Failure with preserved Ejection Fraction (HFpEF) is a growing public health concern with an increasing incidence, high morbidity and mortality and no proven therapy to date. Better characterization of individual pathophysiological implications is mandatory to develop effective therapeutic strategies or preventive programs. Obesity is an important risk factor for the development of HFpEF and also modulates its course possibly by its association with systemic inflammation. However, the role of adipose tissue (AT) inflammation in the development, maintenance and functional impairments in HFpEF has been under-investigated. Dysfunctional AT leads to a shift from a protective adipokine profile to an imbalanced production of pro-inflammatory, pro-oxidant and pro-fibrotic adipokines. Besides depot specific paracrine effects, the overall secretory activity or endocrine effect of AT can be evaluated in peripheral plasma.

The investigators hypothesize that adipose inflammation distinguishes obese HFpEF patients from obese patients without heart failure and that adipose tissue inflammation is a key driver the maintenance and development of HFpEF and determines functional capacity.

In addition the investigators hypothesize that the degree of myocardial inflammatory alterations is more closely related to epicardial tissue alterations than subcutaneous or visceral AT tissue inflammation or peripheral adipokine profiles.

Eligibility criteria: Inclusion Criteria:

* HFpEF: Left ventricular ejection fraction ≥ 50%, NT-pro-BNP ≥ 125ng/l, evidence of structural heart diseases (diastolic dysfunction, left ventricular-hypertrophy or left atrial-dilatation), BMI ≥ 30kg/m²
* Non-HF patients: No history of heart failure, Left ventricular ejection fraction \> 50% and NT-pro-BNP \<125ng/l

Exclusion Criteria:

* Previous cardiac surgery / coronary intervention / myocardial infraction
* Acute coronary syndrome (Serum levels of troponin T \>50 pg/ml)
* Left ventricular ejection fraction \< 50%
* Indication for concomitant valvular surgery
* Planned beating heart coronary bypass surgery
* Hemodynamic instability
* Contraindication for magnetic resonance imaging
* Pregnancy
* Age \< 18 years
* No informed consent possible

Primary outcomes:
measure: Adipose tissue inflammation
timeFrame: Tissue collection during surgery.
Secondary outcomes:
measure: Evaluation of serum adipokine levels
timeFrame: At baseline, before surgery.
measure: Cardiac MRI - Myocardial function
timeFrame: At baseline, before surgery.
measure: Cardiac MRI - Epicardial fat
timeFrame: At baseline, before surgery.
measure: Echocardiography
timeFrame: At baseline, before surgery and at follow-up approximately three months after surgery.
measure: Functional capacity on spiroergometry
timeFrame: At follow-up approximately three months after surgery.
measure: Stress echocardiography
timeFrame: At follow-up approximately three months after surgery.
Other outcomes:
Locations:
city: Leipzig
country: Germany
facility: Heart Centre at University Leipzig
state: Saxony
Study officials:
References: