Adipose Tissue Inflammation in HFpEF

• Conditions: Obesity; Heart Failure With Preserved Ejection Fraction

• Registration Number: NCT04886713
• Lead Sponsor: Heart Center Leipzig - University Hospital

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.

Study Timeline

• Study Start: 2019-11-01
• Study First Submitted: 2021-03-25
• Status Verified: 2021-05
• Study First Submitted QC: 2021-05-10
• Last Update Submitted: 2021-05-10
• Study First Posted: 2021-05-14
• Last Update Posted: 2021-05-14
• Primary Completion: 2021-12-31
• Study Completion: 2022-03-15

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Adipose tissue inflammation	Tissue collection during surgery.	Adipose tissue inflammation and distribution as well as association with adipokines

Secondary Outcome Measures

Name	Time	Method
Cardiac MRI - Myocardial function	At baseline, before surgery.	Myocardial function and extent of myocardial fibrosis.
Echocardiography	At baseline, before surgery and at follow-up approximately three months after surgery.	Measurement of standard echocardiographic parameters of left- and right- ventricular systolic and diastolic function.
Stress echocardiography	At follow-up approximately three months after surgery.	Assessment of echocardiographic parameters of left- and right- ventricular systolic and diastolic function during semi-supine bicycle exercise. These measures include the change of E/E' during exercise for the left ventricle and the change of tricuspid annular plane systolic excursion (TAPSE) during exercise for the right ventricle.
Evaluation of serum adipokine levels	At baseline, before surgery.	Circulating adipokine levels will be measured at a central lab.
Functional capacity on spiroergometry	At follow-up approximately three months after surgery.	Follow-up investigation by spiroergometry to assess post-surgical functional capacity. Measures included Peak Oxygen consumption (VO2 max) and oxygen consumption at anaerobic threshold (AT VO2)
Cardiac MRI - Epicardial fat	At baseline, before surgery.	Extent of epicardial fat.

Trial Locations

Locations (1)

Heart Centre at University Leipzig; 🇩🇪 Leipzig, Saxony, Germany