The Gut Microbiota and Metabolites in HFpEF

NCT06645535 | Enrolling By Invitation

• 1 other identifier: HFpEF 001
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Heart failure (HF) with preserved ejection fraction (HFpEF) has emerged as a critical public health concern. The annual mortality rate for HFpEF is approximately 15%, accompanied by a re-hospitalization rate of nearly 80%. Survival rates over a 5-year period typically range from 25% to 50%. Existing medications effective against HF with reduced ejection fraction (HFrEF) have shown no significant effect on HFpEF. Only the sodium-glucose cotransporter 2 inhibitor (SGLT2i) has demonstrated significant improvements in patient survival and re-hospitalization rates, thus earning a Class IA recommendation in clinical guidelines. HFpEF is characterized as a complex, heterogeneous, multi-organ systemic syndrome primarily associated with risk factors such as advanced age, obesity, metabolic syndrome, type 2 diabetes mellitus (T2DM), hypertension, sedentary lifestyle, coronary atrial disease (CAD), and kidney disease. Therefore, it is crucial to investigate other multi-system disorders closely associated with cardiac diastolic dysfunction to gain a comprehensive understanding of the underlying mechanisms of HFpEF. The human digestive tract harbors a complex and dynamic microbial community known as the gut microbiota, which comprises up to 100 trillion microorganisms and approximately 150 times more genomes than the human genome, often referred to as the "second genome" of the human body. Recent years have seen growing recognition and extensive research into the role of gut microbiota in the pathogenesis and development of cardiovascular diseases. In HFrEF patients, there is a significant decrease in the diversity of gut microbiota, along with changes in its composition and structure. Notably, pathogenic bacteria such as Campylobacter and Candida species exhibit a substantial increase correlating with disease severity, while anti-inflammatory bacteria like Brauteria demonstrate a marked decrease. Furthermore, gut microbiota can influence the host's cardiometabolic traits through the modulation of both its own and host-produced metabolites. HFpEF is increasingly considered a metabolic disease. Comorbidities associated with HFpEF, including obesity, T2DM, metabolic syndrome, hypertension, and coronary artery disease (CAD), have been reported to be closely related to gut microbiota. However, the relationship between gut microbiota and HFpEF is still not fully understood. A recent study indicates that indole-3-propionic acid (IPA) could attenuate diastolic and metabolic dysfunction and mitigate gut microbiota dysbiosis in an HFpEF mouse model. Several clinical studies have noted alterations in microbial metabolites such as short-chain fatty acids (SCFAs), and trimethylamine N-oxide (TMAO) in HFpEF patients. It is now well recognized that targeting the gut microbiome and its metabolites represents a promising novel therapeutic strategy for managing cardiovascular diseases. Therefore, this study is to investigate the changes and function of gut microbiota and metabolites in HFpEF.

Conditions

HFpEF - Heart Failure With Preserved Ejection Fraction

Keywords

gut microbiota; metabolites; HFpEF

Outcome Measures

Primary Outcomes (1)

• Death and rehospitalization

  All-cause death and rehospitalization due to cardiac causes within 3 years

  3 years

Secondary Outcomes (1)

• Health-related quality of life

  3 years.

Study Arms (3)

HFpEF group

Patients with heart failure with preserved ejection fraction.

HFrEF group

Patients with heart failure with reduced ejection fraction.

Control group

Control participants without heart failure.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The patients who met the inclusion criteria of this cohort study were consecutively screened in the Department of Cardiovascular Medicine, the First Affiliated Hospital of Nanjing Medical University.

You may qualify if:

• Male or female, ≥18 years old;
• With symptoms and signs of chronic heart failure, NYHA class II-IV;
• LVEF≥50% according to the most recent echocardiography before screening, and no previous record of LVEF\<50%;
• BNP \>35 pg/mL, or NT-proBNP \>125 pg/mL;
• Comply with at least one of the following:
• (1) LVMI ≥ 115g/m2 (men) 95g/m2 (women); (2) RWT \> 0.42; R (3) E/e '\>15; (4) septal e '\<7cm/s or lateral e' \<10cm/s or mean e '\<8cm/s; (5) TVR\>2.8m/s or PASP\>35mmHg.

You may not qualify if:

• Patients with confirmed chronic or acute renal insufficiency (stage II-IV)

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

the First Affiliated Hospital of Nanjing Medical University

Naning, Jiangsu, 210000, China

Location

Related Publications (20)

• Kinugasa Y, Nakamura K, Kamitani H, Hirai M, Yanagihara K, Kato M, Yamamoto K. Trimethylamine N-oxide and outcomes in patients hospitalized with acute heart failure and preserved ejection fraction. ESC Heart Fail. 2021 Jun;8(3):2103-2110. doi: 10.1002/ehf2.13290. Epub 2021 Mar 18.

  PMID: 33734604 BACKGROUND

• Beale AL, O'Donnell JA, Nakai ME, Nanayakkara S, Vizi D, Carter K, Dean E, Ribeiro RV, Yiallourou S, Carrington MJ, Marques FZ, Kaye DM. The Gut Microbiome of Heart Failure With Preserved Ejection Fraction. J Am Heart Assoc. 2021 Jul 6;10(13):e020654. doi: 10.1161/JAHA.120.020654. Epub 2021 Jul 2.

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• Wang YC, Koay YC, Pan C, Zhou Z, Tang W, Wilcox J, Li XS, Zagouras A, Marques F, Allayee H, Rey FE, Kaye DM, O'Sullivan JF, Hazen SL, Cao Y, Lusis AJ. Indole-3-Propionic Acid Protects Against Heart Failure With Preserved Ejection Fraction. Circ Res. 2024 Feb 16;134(4):371-389. doi: 10.1161/CIRCRESAHA.123.322381. Epub 2024 Jan 24.

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• Pfeffer MA, Shah AM, Borlaug BA. Heart Failure With Preserved Ejection Fraction In Perspective. Circ Res. 2019 May 24;124(11):1598-1617. doi: 10.1161/CIRCRESAHA.119.313572.

  PMID: 31120821 BACKGROUND

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Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, plasma, serum samples, and stool samples were obtained from participants.

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Geriatric Cardiology

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: October 17, 2024
• Study Start: June 30, 2022
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)