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Obesity, severe overweight, is a growing problem worldwide and increases the risk of heart failure, especially a type called heart failure with preserved ejection fraction (HFpEF).
In HFpEF, the heart becomes stiffer. This makes it harder for the heart to fill with blood, which can lead to shortness of breath during physical activity.
In the Netherlands, 15% of the population has obesity. In South Limburg, this is even higher at 19%. Among people with HFpEF, obesity is much more common: about 50% of these patients have obesity.
Life expectancy in people with HFpEF is poor, and current treatment mainly focuses on reducing symptoms. Early recognition and treatment of risk factors, such as obesity, are therefore very important.
This study includes about 250 people with obesity. Using a heart ultrasound and tests of blood and fat tissue, we will look for early signs of HFpEF and study the effects of weight loss. The measurements will be repeated after 1 and 2 years.
The goal of this study is to better understand how obesity contributes to HFpEF and how weight loss affects the heart. This research may help improve future treatments for patients with HFpEF.
The study is an observational, longitudinal cohort study, with extensive phenotyping at baseline and at 1- and 2 years follow-up after Metabolic bariatric surgery. The baseline assessment corresponds to the intake phase at the obesity clinic. All patients will undergo Metabolic Bariatric Surgery and multi-disciplinary treatment focused on life style change. All patients will then be followed longitudinally with repeated assessments after 1- and 2 years follow-up.
The primary objective of this study is:
I) To determine the prevalence of HFpEF and (pre)-HFpEF in patients with obesity requesting MBS.
Secondary objective(s):
I) Evaluate the differences between the three study groups (HFpEF vs preHFpEF vs patients without HF) concerning pathophysiologic mediators, functional status, QoL and medical history/demographics at baseline.
II) Evaluate the prevalence of (pre-)HFpEF at 1- and 2 years after MBS, i.e. evaluating the reclassification (transition) in disease groups from baseline.
III) Evaluate changes in cardiac function and pathophysiologic mediators from baseline to 1- and 2 years after MBS.
IV) Evaluate changes in quality of life (QoL) and functional capacity measured as change in 6-minute walking test distance from baseline to 1- and 2 years after MBS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with obesity grade 2 or higher presenting at the Dutch obesity clinic requesting MBS. | Our study population consists of patients presenting at the DOC South requesting Metabolic bariatric surgery (MBS). 10-15 new patients present themselves weekly at the DOC South, from which study participants can be recruited. Our population is 35 years or older and has no previous history of a reduced ejection fraction, severe cardiac valve defects of severe congenital cardiac defects. Our population does not have a previous history of metabolic bariatric surgery. |
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| Measure | Description | Time Frame |
|---|---|---|
| Prevalence of HFpEF and (pre)-HFpEF in patients with obesity at baseline. | The primary endpoint of this study is the total percentage of individuals with obesity who have (pre-)HFpEF within our study population. This will be measured by performing echocardiography, physical examination, and measuring natriuretic peptides. For the definition of HFpEF, we use the diagnostic criteria from the European HF guidelines. (12)
| Baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Delta in total percentage of (pre-)HFpEF cases after metabolic bariatric surgery at 1-and 2 years follow-up. | 2 years | |
| Mean difference between HFpEF, pre-HFpEF and patients without HF concerning low grade inflammation (High sensitivity C-reactive protein). |
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Inclusion Criteria:
Exclusion Criteria:
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Our study population consists of patients presenting at the DOC South requesting metabolic bariatric surgery. Our predetermined sample size was set at 250 participants.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Lukas Peeters, Master of Science in Medicine | Contact | +32479092470 | luka.peeters@zuyderland.nl |
| Name | Affiliation | Role |
|---|---|---|
| Sandra van Wijk, Dr. | Zuyderland Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Zuyderland Medisch Centrum Heerlen | Recruiting | Heerlen | Limburg | 6419PC | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34453165 | Background | Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, Capodanno D, Conradi L, De Bonis M, De Paulis R, Delgado V, Freemantle N, Gilard M, Haugaa KH, Jeppsson A, Juni P, Pierard L, Prendergast BD, Sadaba JR, Tribouilloy C, Wojakowski W; ESC/EACTS Scientific Document Group. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2022 Feb 12;43(7):561-632. doi: 10.1093/eurheartj/ehab395. No abstract available. | |
| 37900360 |
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| ID | Term |
|---|---|
| D054144 | Heart Failure, Diastolic |
| D009765 | Obesity |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
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Visceral and subcutaneous adipose tissue biopsies
Difference in High sensitivity C-reactive protein (mg/L) at baseline
| Baseline |
| Mean difference between HFpEF, pre-HFpEF and patients without HF concerning low grade inflammation (IL6). | Difference in interleukin-6 (pg/ml) at baseline | Baseline |
| Mean difference between HFpEF, pre-HFpEF and patients without HF concerning NT-proBNP | Difference in NT-proBNP (ng/L) at baseline. | Baseline |
| Mean difference between HFpEF, pre-HFpEF and patients without HF concerning antropomorphic measurements (BMI). | Difference in BMI (Kg2/m) at baseline. | Baseline |
| Mean difference between HFpEF, pre-HFpEF and patients without HF concerning antropomorphic measurements (Waist-to-Height ratio). | Difference in Waist-to-Height ratio (Waist circumference (cm) divided by height (cm)) at baseline. | Baseline |
| Mean difference between HFpEF, pre-HFpEF and patients without HF concerning adipocyte cell size. | Difference in adipocyte cell size in diameter (micrometers) and cross sectional area (square micrometers) at baseline. | Baseline |
| Mean difference between HFpEF, pre-HFpEF and patients without HF concerning adipose tissue hyperplasia | Difference in adipose tissue hyperplasia in total cell number and adipcyte cell density (cells/mm2) at baseline. | Baseline |
| Delta in low grade inflammation (High sensitivity C-reactive protein) from baseline to 1- and 2 year follow-up. | Changes in High sensitivity C-reactive protein (mg/L), from baseline to 1- and 2 years after metabolic bariatric surgery. | 2 years |
| Delta in low grade inflammation (IL-6) from baseline to 1- and 2 year follow-up | Changes in IL-6 from baseline (pg/ml), from baseline to 1- and 2 years after metabolic bariatric surgery. | 2 years |
| Delta in NTproBNP from baseline to 1- and 2 year follow-up. | Changes in N-terminal brain natriuretic peptide (ng/L), from baseline to 1- and 2 years after metabolic bariatric surgery. | 2 years |
| Delta in functional capacity from baseline to 1- and 2 years folllow-up | Change in the six-minute walking test distance from baseline to 1- and 2 years follow-u after metabolic bariatric surgery. | 2 Years |
| Change in antropomorphic measures (BMI) from baseline to 1- and 2 year follow-up | Changes in BMI (Kg2/m), from baselin to 1- and 2 years after metabolic bariatric surgery. | 2 years |
| Change in antropomorphic measures (Waist-to-height ratio) from baseline to 1- and 2 year follow-up | Changes in Waist-to-height ratio (Waist circumference (cm) divided by height (cm)), from baseline to 1-and 2 years after metabolic surgery. | 2 years |
| Background |
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| 35441470 | Background | Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, Lingvay I, McGowan BM, Oral TK, Rosenstock J, Wadden TA, Wharton S, Yokote K, Kushner RF; STEP 1 Study Group. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022 Aug;24(8):1553-1564. doi: 10.1111/dom.14725. Epub 2022 May 19. |
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| 29298158 | Background | Carroll RW, Stubbs RS, Krebs JD. Weight and Metabolic Outcomes 12 Years after Gastric Bypass. N Engl J Med. 2018 Jan 4;378(1):93. doi: 10.1056/NEJMc1714001. No abstract available. |
| 31082301 | Background | Sepehrvand N, Alemayehu W, Dyck GJB, Dyck JRB, Anderson T, Howlett J, Paterson I, McAlister FA, Ezekowitz JA. External Validation of the H2F-PEF Model in Diagnosing Patients With Heart Failure and Preserved Ejection Fraction. Circulation. 2019 May 14;139(20):2377-2379. doi: 10.1161/CIRCULATIONAHA.118.038594. No abstract available. |
| 37622666 | Background | McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Skibelund AK; ESC Scientific Document Group. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023 Oct 1;44(37):3627-3639. doi: 10.1093/eurheartj/ehad195. No abstract available. |
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| 28381470 | Background | Obokata M, Reddy YNV, Pislaru SV, Melenovsky V, Borlaug BA. Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure With Preserved Ejection Fraction. Circulation. 2017 Jul 4;136(1):6-19. doi: 10.1161/CIRCULATIONAHA.116.026807. Epub 2017 Apr 5. |
| 23271790 | Background | Ho JE, Lyass A, Lee DS, Vasan RS, Kannel WB, Larson MG, Levy D. Predictors of new-onset heart failure: differences in preserved versus reduced ejection fraction. Circ Heart Fail. 2013 Mar;6(2):279-86. doi: 10.1161/CIRCHEARTFAILURE.112.972828. Epub 2012 Dec 27. |
| 33866828 | Background | Tromp J, Claggett BL, Liu J, Jackson AM, Jhund PS, Kober L, Widimsky J, Boytsov SA, Chopra VK, Anand IS, Ge J, Chen CH, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, Van Veldhuisen DJ, Zannad F, Zile MR, Rizkala AR, Inubushi-Molessa A, Lefkowitz MP, Shi VC, McMurray JJV, Solomon SD, Lam CSP; PARAGON-HF Investigators. Global Differences in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial. Circ Heart Fail. 2021 Apr;14(4):e007901. doi: 10.1161/CIRCHEARTFAILURE.120.007901. Epub 2021 Apr 19. |
| 12151467 | Background | Kenchaiah S, Evans JC, Levy D, Wilson PW, Benjamin EJ, Larson MG, Kannel WB, Vasan RS. Obesity and the risk of heart failure. N Engl J Med. 2002 Aug 1;347(5):305-13. doi: 10.1056/NEJMoa020245. |
| 37622681 | Background | Kosiborod MN, Abildstrom SZ, Borlaug BA, Butler J, Rasmussen S, Davies M, Hovingh GK, Kitzman DW, Lindegaard ML, Moller DV, Shah SJ, Treppendahl MB, Verma S, Abhayaratna W, Ahmed FZ, Chopra V, Ezekowitz J, Fu M, Ito H, Lelonek M, Melenovsky V, Merkely B, Nunez J, Perna E, Schou M, Senni M, Sharma K, Van der Meer P, von Lewinski D, Wolf D, Petrie MC; STEP-HFpEF Trial Committees and Investigators. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2023 Sep 21;389(12):1069-1084. doi: 10.1056/NEJMoa2306963. Epub 2023 Aug 25. |
| 39920805 | Background | van Dalen BM, Chin JF, Motiram PA, Hendrix A, Emans ME, Brugts JJ, Westenbrink BD, de Boer RA. Challenges in the diagnosis of heart failure with preserved ejection fraction in individuals with obesity. Cardiovasc Diabetol. 2025 Feb 7;24(1):71. doi: 10.1186/s12933-025-02612-z. |
| 32902195 | Background | Snelder SM, de Groot-de Laat LE, Biter LU, Castro Cabezas M, Pouw N, Birnie E, Boxma-de Klerk BM, Klaassen RA, Zijlstra F, van Dalen BM. Subclinical cardiac dysfunction in obesity patients is linked to autonomic dysfunction: findings from the CARDIOBESE study. ESC Heart Fail. 2020 Dec;7(6):3726-3737. doi: 10.1002/ehf2.12942. Epub 2020 Sep 9. |
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| D009748 |
| Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |