Adipose Tissue Inflammation in HFpEF (SLIM-HFpEF)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Diagnostic test: Adipose and myocardial tissue sampling; Diagnostic test: Cardiac magnetic resonance imaging; Diagnostic test: Cardiopulmonary exercise testing

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 Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

• Study Contact: Name: Karl-Patrik Kresoja, MD; Phone Number: +49 341 865 252596; Email: karl-patrik.kresoja@medizin.uni-leipzig.de

Study Locations

• Germany
  • Saxony
    • Leipzig, Saxony, Germany, 04289
      • Recruiting
      • Heart Centre at University Leipzig
      • Contact: Philipp Lurz, MD, PhD; Email: philipp.lurz@medizin.uni-leipzig.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

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 Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Obese HFpEF; Left ventricular-EF ≥ 50%, N-terminal-pro-brain natriuretic peptide (NT-proBNP) ≥ 125ng/l, evidence of structural heart diseases (diastolic dysfunction, Left ventricular-hypertrophy or Left atrial-dilatation) BMI ≥30 kg/m²	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.; Diagnostic test: 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; Diagnostic test: 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.
Obese controls; No history of heart failure, Left ventricular-EF > 50% and NT-pro-BNP <125ng/l, BMI ≥ 30kg/m²	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.; Diagnostic test: 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; Diagnostic test: 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.
Lean control; No history of heart failure, Left ventricular-EF > 50% and NT-pro-BNP <125ng/l, BMI < 30kg/m²	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.; Diagnostic test: 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; Diagnostic test: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adipose tissue inflammation	Adipose tissue inflammation and distribution as well as association with adipokines	Tissue collection during surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of serum adipokine levels	Circulating adipokine levels will be measured at a central lab.	At baseline, before surgery.
Cardiac MRI - Myocardial function	Myocardial function and extent of myocardial fibrosis.	At baseline, before surgery.
Cardiac MRI - Epicardial fat	Extent of epicardial fat.	At baseline, before surgery.
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.
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.
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.

Collaborators and Investigators

• Sponsor: Heart Center Leipzig - University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2019
• Primary Completion (ANTICIPATED): December 31, 2021
• Study Completion (ANTICIPATED): March 15, 2022

Study Registration Dates

• First Submitted: March 25, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (ACTUAL): May 14, 2021

Study Record Updates

• Last Update Posted (ACTUAL): May 14, 2021
• Last Update Submitted That Met QC Criteria: May 10, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Heart Failure; Inflammation
• Other Study ID Numbers: SLIM-HFpEF V1.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No