OBESE-HFpEF: Towards Preventing Obesity Related HFpEF

Official title

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

Overview

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.

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.

Primary outcome measures

• Prevalence of HFpEF and (pre)-HFpEF in patients with obesity at baseline. [Time frame: Baseline]

Secondary outcome measures (12)

• Delta in total percentage of (pre-)HFpEF cases after metabolic bariatric surgery at 1-and 2 years follow-up. [Time frame: 2 years]
• Mean difference between HFpEF, pre-HFpEF and patients without HF concerning low grade inflammation (High sensitivity C-reactive protein). [Time frame: Baseline]
• Mean difference between HFpEF, pre-HFpEF and patients without HF concerning low grade inflammation (IL6). [Time frame: Baseline]
• Mean difference between HFpEF, pre-HFpEF and patients without HF concerning NT-proBNP [Time frame: Baseline]
• Mean difference between HFpEF, pre-HFpEF and patients without HF concerning antropomorphic measurements (BMI). [Time frame: Baseline]
• Mean difference between HFpEF, pre-HFpEF and patients without HF concerning antropomorphic measurements (Waist-to-Height ratio). [Time frame: Baseline]
• Mean difference between HFpEF, pre-HFpEF and patients without HF concerning adipocyte cell size. [Time frame: Baseline]
• Mean difference between HFpEF, pre-HFpEF and patients without HF concerning adipose tissue hyperplasia [Time frame: Baseline]
• Delta in low grade inflammation (High sensitivity C-reactive protein) from baseline to 1- and 2 year follow-up. [Time frame: 2 years]
• Delta in low grade inflammation (IL-6) from baseline to 1- and 2 year follow-up [Time frame: 2 years]
• Delta in NTproBNP from baseline to 1- and 2 year follow-up. [Time frame: 2 years]
• Delta in functional capacity from baseline to 1- and 2 years folllow-up [Time frame: 2 Years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

Netherlands · 1 center

• Zuyderland Medisch Centrum Heerlen — Heerlen

Publications

• 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 PMID 34453165
• 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 Sep 28;15(9):e46153. doi: 10.7759/cureus.46153. eCollection 2023 Sep. PMID 37900360
• 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 Nov 22;13:947147. doi: 10.3389/fimmu.2022.947147. eCollection 2022. PMID 36483560
• Kawai T, Autieri MV, Scalia R. Adipose tissue inflammation and metabolic dysfunction in obesity. Am J Physiol Cell Physiol. 2021 Mar 1;320(3):C375-C391. doi: 10.1152/ajpcell.00379.2020. Epub 2020 Dec 23. PMID 33356944
• 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 Feb 3;118(18):3434-3450. doi: 10.1093/cvr/cvac120. PMID 35880317
• 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. PMID 35441470
• 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 Mar 1;67(8):895-903. doi: 10.1016/j.jacc.2015.12.016. PMID 26916477
• Berger S, Meyre P, Blum S, Aeschbacher S, Ruegg M, Briel M, Conen D. Bariatric surgery among patients with heart failure: a systematic review and meta-analysis. Open Heart. 2018 Dec 9;5(2):e000910. doi: 10.1136/openhrt-2018-000910. eCollection 2018. PMID 30613414

Identifiers

NCT: NCT07539766 · NL-009536

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗