OBESE-HFpEF: Towards Preventing Obesity Related HFpEF (OBESE-HFpEF)

OBESE-HFpEF: Prevalence and Mediators of Heart Failure (Preserved Ejection Fraction) in the Dutch Obesity Clinic South - Towards Preventing Obesity Related HFpEF''

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Obesity (Disorder); Heart Failure and Preserved Ejection Fraction

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Lukas Peeters, Master of Science in Medicine; Phone Number: +32479092470; Email: luka.peeters@zuyderland.nl

Study Locations

• Netherlands
  • Limburg
    • Heerlen, Limburg, Netherlands, 6419PC
      • Recruiting
      • Zuyderland Medisch Centrum Heerlen
      • Contact: Lukas Peeters, Master of Science in Medicine; Phone Number: +32479092470; Email: luka.peeters@zuyderland.nl
      • Sub-Investigator: Lukas Peeters, Master of Science in Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Our study population consists of patients presenting at the DOC South requesting metabolic bariatric surgery. Our predetermined sample size was set at 250 participants.

Description

Inclusion Criteria:

• Age ≥ 35 years
• Eligible for surgical treatment for obesity, according to the Dutch guideline, i.e. a BMI ≥ 40 kg/m2 or a BMI ≥ 35 kg/m2 with one or more comorbidities associated with obesity. (23)

Exclusion Criteria:

• Inability to provide informed consent.
• A BMI >60 kg/m2
• Inability of undergoing metabolic bariatric surgery safely.
• Inability to undergo the study measurement/tests.
• Not proficient in the Dutch language
• A medical history of a reduced LVEF at any time, history of severe cardiac valve defects or severe congenital cardiac defects.
• A medical history of previous metabolic bariatric surgery.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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); HFpEF is defined as follows :symptoms and signs of HF (table II, at least 1 typical/more specific or 2 less typical/less specific)evidence of structural and/or functional cardiac abnormalities demonstrated by echocardiography (table III) and/or raised natriuretic peptides (NPs)LVEF ≥50%; Pre-HFpEF:No symptoms or signs of HF (table II).Evidence of structural and/or functional cardiac abnormalities demonstrated by echocardiography (table III) and/or raised natriuretic peptides (NPs)LVEF ≥50%,; Individuals with obesity who do not meet the criteria above are consequently the patients that are not as having (pre-)HFpEF.	Baseline

Secondary Outcome Measures

Outcome Measure	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).	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

Collaborators and Investigators

• Sponsor: Zuyderland Medisch Centrum
• Investigators: Principal Investigator: Sandra van Wijk, Dr., Zuyderland Medical Center

Publications and helpful links

General Publications

• Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J 2022 -02-12;43(7):561-632.
• Zain S, Shamshad T, Kabir A, Khan AA. Epicardial Adipose Tissue and Development of Atrial Fibrillation (AFIB) and Heart Failure With Preserved Ejection Fraction (HFpEF). Cureus 2023 -09;15(9):e46153.
• Li C, Qin D, Hu J, Yang Y, Hu D, Yu B. Inflamed adipose tissue: A culprit underlying obesity and heart failure with preserved ejection fraction. Front Immunol 2022 -11-22;13.
• Kawai T, Autieri MV, Scalia R. Adipose tissue inflammation and metabolic dysfunction in obesity. American Journal of Physiology-Cell Physiology 2021 -03-01;320(3):C375.
• Borlaug BA, Jensen MD, Kitzman DW, Lam CSP, Obokata M, Rider OJ. Obesity and heart failure with preserved ejection fraction: new insights and pathophysiological targets. Cardiovasc Res 2023 -02-03;118(18):3434-3450.
• Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab 2022 -08;24(8):1553-1564.
• Shimada YJ, Tsugawa Y, Brown DFM, Hasegawa K. Bariatric Surgery and Emergency Department Visits and Hospitalizations for Heart Failure Exacerbation: Population-Based, Self-Controlled Series. J Am Coll Cardiol 2016 -03-01;67(8):895-903.
• Berger S, Meyre P, Blum S, Aeschbacher S, Ruegg M, Briel M, et al. Bariatric surgery among patients with heart failure: a systematic review and meta-analysis. Open Heart 2018;5(2):e000910.
• Courcoulas AP, Belle SH, Neiberg RH, Pierson SK, Eagleton JK, Kalarchian MA, et al. Three-Year Outcomes of Bariatric Surgery vs Lifestyle Intervention for Type 2 Diabetes Mellitus Treatment: A Randomized Clinical Trial. JAMA Surg 2015 -10;150(10):931-940.
• Carroll RW, Stubbs RS, Krebs JD. Weight and Metabolic Outcomes 12 Years after Gastric Bypass. N Engl J Med 2018 -01-04;378(1):93.
• Sepehrvand N, Alemayehu W, Dyck GJB, Dyck JRB, Anderson T, Howlett J, et al. External Validation of the H2F-PEF Model in Diagnosing Patients With Heart Failure and Preserved Ejection Fraction. Circulation 2019 -05-14;139(20):2377-2379.
• McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2023 -10-01;44(37):3627-3639.
• Chockalingam A. "Obesity-Years" Burden May Predict Reversibility in Heart Failure With Preserved Ejection Fraction. Front Cardiovasc Med 2022;9:821829.
• 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 -07-04;136(1):6-19.
• Ho JE, Lyass A, Lee DS, Vasan RS, Kannel WB, Larson MG, et al. Predictors of new-onset heart failure: differences in preserved versus reduced ejection fraction. Circ Heart Fail 2013 -03;6(2):279-286.
• Tromp J, Claggett BL, Liu J, Jackson AM, Jhund PS, Køber L, et al. Global Differences in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial. Circ Heart Fail 2021 -04;14(4):e007901.
• 5.Kenchaiah S, Evans JC, Levy D, Wilson PWF, Benjamin EJ, Larson MG, et al. Obesity and the Risk of Heart Failure. New England Journal of Medicine 2002 August 1;347(5):305-313.
• 4.Kosiborod MN, Abildstrøm SZ, Borlaug BA, Butler J, Rasmussen S, Davies M, et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. New England Journal of Medicine 2023 September 20;389(12):1069-1084.
• 3.van Dalen BM, Chin JF, Motiram PA, Hendrix A, Emans ME, Brugts JJ, et al. Challenges in the diagnosis of heart failure with preserved ejection fraction in individuals with obesity. Cardiovasc Diabetol 2025 -02-07;24(1):71.
• 2.Snelder SM, de Groot-de Laat LE, Biter LU, Castro Cabezas M, Pouw N, Birnie E, et al. Subclinical cardiac dysfunction in obesity patients is linked to autonomic dysfunction: findings from the CARDIOBESE study. ESC Heart Fail 2020 -12;7(6):3726-3737.
• 1.Kosyakovsky LB, Liu EE, Wang JK, Myers L, Parekh JK, Knauss H, et al. Uncovering Unrecognized Heart Failure With Preserved Ejection Fraction Among Individuals With Obesity and Dyspnea. Circ Heart Fail 2024 -05;17(5):e011366.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: January 30, 2026
• First Submitted That Met QC Criteria: April 13, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; Prospective; Heart Failure with preserved ejection fraction; Metabolic Bariatric Surgery
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Nutrition Disorders; Heart Diseases; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Heart Failure; Obesity; Heart Failure, Diastolic
• Other Study ID Numbers: NL-009536

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