Adipose Tissue Inflammation in HFpEF

Obesity Clinical Trial

— SLIM-HFpEF  

Official title:

Adipose Tissue Inflammation in the Development, Maintenance and Functional Impairments in Heart Failure With Preserved Ejection Fraction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04886713
• Other study ID #: SLIM-HFpEF V1.0
• Status: Recruiting
• Start date: November 1, 2019
• Est. completion date: March 15, 2022

Study information

• Verified date: May 2021
• Source: Heart Center Leipzig - University Hospital
• Contact: Karl-Patrik Kresoja, MD
• Phone: +49 341 865 252596
• Email: karl-patrik.kresoja[@]medizin.uni-leipzig.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 15, 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction
• Inflammation
• Obesity

Intervention

Diagnostic Test:
• Adipose and myocardial tissue sampling
After median sternotomy tissue samples will be collected from the epicardial space, the abdominal wall and the myocardium.
• Cardiac magnetic resonance imaging
Magnetic resonance imaging will be performed at 1.5 Tesla ('Intera', Philips Medical Systems, Best, The Netherlands). All subjects will be examined in the supine position with initial anatomy scans to cover the thorax to the first sacral vertebrae. The magnetic resonance imaging protocol is summarized in Figure 4. The following imaging parameters will be acquired: Biventricular end-diastolic and end-systolic volume, ejection fraction, stroke volume Biventricular mass, wall thickness T1 mapping; native and > 10 minutes post contrast injection as an estimate of left ventricular diffuse fibrosis and extracellular volume Late enhancement for detection of regional fibrosis and scar Myocardial feature tracking for analysis of deformation/motion Epicardial fat volume
• Cardiopulmonary exercise testing
After completion of a regular cardiac rehabilitation program patients are scheduled to undergo their discharge examination at 3 to 4 weeks after the operation in order to be functionally characterized. Cardiopulmonary exercise testing will be performed, if possible by patients condition, on a mechanically braked bicycle ergometer and respiratory gas exchange analysis via a mouthpiece or facemask.

Locations

Country	Name	City	State
Germany	Heart Centre at University Leipzig	Leipzig	Saxony

Sponsors (1)

Lead Sponsor	Collaborator
Heart Center Leipzig - University Hospital

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adipose tissue inflammation	Adipose tissue inflammation and distribution as well as association with adipokines	Tissue collection during surgery.
Secondary	Evaluation of serum adipokine levels	Circulating adipokine levels will be measured at a central lab.	At baseline, before surgery.
Secondary	Cardiac MRI - Myocardial function	Myocardial function and extent of myocardial fibrosis.	At baseline, before surgery.
Secondary	Cardiac MRI - Epicardial fat	Extent of epicardial fat.	At baseline, before surgery.
Secondary	Echocardiography	Measurement of standard echocardiographic parameters of left- and right- ventricular systolic and diastolic function.	At baseline, before surgery and at follow-up approximately three months after surgery.
Secondary	Functional capacity on spiroergometry	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)	At follow-up approximately three months after surgery.
Secondary	Stress echocardiography	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.	At follow-up approximately three months after surgery.