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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
| |
| Obese controls | No history of heart failure, Left ventricular-EF > 50% and NT-pro-BNP <125ng/l, BMI ≥ 30kg/m² |
| |
| Lean control | No history of heart failure, Left ventricular-EF > 50% and NT-pro-BNP <125ng/l, BMI < 30kg/m² |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Adipose and myocardial tissue sampling | Diagnostic Test | After median sternotomy tissue samples will be collected from the epicardial space, the abdominal wall and the myocardium. |
| Measure | Description | Time Frame |
|---|---|---|
| Adipose tissue inflammation | Adipose tissue inflammation and distribution as well as association with adipokines | Tissue collection during surgery. |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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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:
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Karl-Patrik Kresoja, MD | Contact | +49 341 865 252596 | karl-patrik.kresoja@medizin.uni-leipzig.de |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Heart Centre at University Leipzig | Recruiting | Leipzig | Saxony | 04289 | Germany |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D005080 | Exercise Test |
| ID | Term |
|---|---|
| D006334 | Heart Function Tests |
| D003935 | Diagnostic Techniques, Cardiovascular |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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| Cardiac magnetic resonance imaging | 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:
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| Cardiopulmonary exercise testing | 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. |
|
| 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. |
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012129 | Respiratory Function Tests |
| D003948 | Diagnostic Techniques, Respiratory System |
| D016552 | Ergometry |
| D008919 | Investigative Techniques |