Adipose Tissue Inflammation in HFpEF

NCT ID: NCT04886713

Last Updated: 2021-05-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

30 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-11-01

Study Completion Date

2022-03-15

Brief Summary

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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

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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.

Conditions

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Heart Failure With Preserved Ejection Fraction Obesity

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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

Adipose and myocardial tissue sampling

Intervention Type DIAGNOSTIC_TEST

After median sternotomy tissue samples will be collected from the epicardial space, the abdominal wall and the myocardium.

Cardiac magnetic resonance imaging

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Adipose and myocardial tissue sampling

Intervention Type DIAGNOSTIC_TEST

After median sternotomy tissue samples will be collected from the epicardial space, the abdominal wall and the myocardium.

Cardiac magnetic resonance imaging

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Adipose and myocardial tissue sampling

Intervention Type DIAGNOSTIC_TEST

After median sternotomy tissue samples will be collected from the epicardial space, the abdominal wall and the myocardium.

Cardiac magnetic resonance imaging

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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.

Interventions

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Adipose and myocardial tissue sampling

After median sternotomy tissue samples will be collected from the epicardial space, the abdominal wall and the myocardium.

Intervention Type 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

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Heart Center Leipzig - University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Philipp Lurz

Clinical Investigator, Professor, Managing Senior Physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Heart Centre at University Leipzig

Leipzig, Saxony, Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Karl-Patrik Kresoja, MD

Role: CONTACT

+49 341 865 252596

Facility Contacts

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Karl-Patrik Kresoja, MD

Role: primary

0341 865 252596

Philipp Lurz, MD, PhD

Role: backup

Other Identifiers

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SLIM-HFpEF V1.0

Identifier Type: -

Identifier Source: org_study_id

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