Effect of Acute Cardiovascular Disease on Microbiome (MIAMI)

The Influence of a Symptomatic Coronary Artery and Peripheral Arterial Disease on the Oral-enteral Microbiome and Downstream Microbiome-dependent Metabolites

Atherosclerotic diseases such as coronary artery disease (CAD) and peripheral arterial disease (PAD) are the leading cause of morbidity and mortality in the industrialized world.

An interaction between the development of atherosclerotic diseases and the oral and enteral microbiome composition has already been demonstrated in the past. The microbiome is a double-edged sword which can convey protective and detrimental cardiovascular effects. While it can promote the development of atherosclerosis through the production of atherogenic metabolites such as trimethylamine N-oxide (TMAO) it can also generate a protective effect through the production of metabolites such as short chain fatty acids (SCFA). Preliminary data suggest that atherosclerotic disease itself can induce a dysbiosis of the microbiome.

Aim of this study is to determine the differences in coronary artery disease and peripheral arterial disease on the oral-enteral microbiome axis and downstream microbiome-dependent metabolites.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Coronary Artery Disease; Peripheral Arterial Disease; Acute Coronary Syndrome; Microbial Colonization; Critical Limb Ischemia
• Intervention / Treatment: Other: Standard of care treatment

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• Germany
  • NRW
    • Essen, NRW, Germany, 45147
      • University of Essen, Clinic of Cardiology and Angiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients older than 18 years presenting to the clinic with acute coronary syndrome (ACS), chronic coronary syndrome (CCS) or critical limb threatening ischemia (CLI) who can be included into the study within a 24 hours time frame after presentation.

Description

Inclusion Criteria:

• >18 years
• patient consent
• CCS, ACS or CLI
• angiographical confirmed peripheral or coronary artery disease

Exclusion Criteria:

• pregnancy/lactation period
• current antibiotic treatment or in the past 3 months
• chronic inflammatory bowel disease
• short bowel syndrome
• artificial bowel outlet
• persistent diarrhea or vomiting in the past 3 months
• simultaneous participation in another interfering nutrition study
• active chemo or radiation therapy

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Acute Coronary Syndrome (ACS); Patients presenting to the clinic with acute coronary syndrome. This includes: ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris (UAP) with confirmed diagnosis of coronary artery disease.	Other: Standard of care treatment; Standard of care treatment including percutaneous interventions was performed in all participants.
Chronic Coronary Syndrome (CCS); Patients presenting to the clinic with chronic coronary syndrome and confirmed diagnosis of coronary artery disease.	Other: Standard of care treatment; Standard of care treatment including percutaneous interventions was performed in all participants.
Critical limb ischemia (CLI); Patients presenting to the clinic with critical limb ischemia. This includes: Resting limb pain (Fontaine III), ulcerations (Fontaine IV) and Ankle brachial index (ABI) < 0,6 and confirmed diagnosis of peripheral artery disease.	Other: Standard of care treatment; Standard of care treatment including percutaneous interventions was performed in all participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of enteral microbiome composition after presentation with ACS/CCS/CLI	Stool samples are collected at the below mentioned time points. DNA isolation will be performed with consecutive 16S-RNA analysis and cluster analysis.	Sampling will be performed within 24 hours of presentation to the clinic, at day 3, day 7, day 14 and at day 28 (+/- 2 days) after initial presentation.
Change of oral microbiome composition after presentation with ACS/CCS/CLI	Oral samples are collected at the below mentioned time points. DNA isolation will be performed with consecutive 16S-RNA analysis and cluster analysis.	Sampling will be performed within 24 hours of presentation to the clinic, at day 3, day 7, day 14 and at day 28 (+/- 2 days) after initial presentation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of TMAO serum levels after presentation with ACS/CCS/CLI	Blood samples are collected at the below mentioned time points. TMAO serum levels will be measured by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).	Sampling will be performed within 24 hours of presentation to the clinic and at day 28 (+/- 2 days) after initial presentation.
Change of SCFA serum levels after presentation with ACS/CCS/CLI	Blood samples are collected at the below mentioned time points. SCFA serum levels will be measured by high-performance liquid chromatography (HPLC).	Sampling will be performed within 24 hours of presentation to the clinic and at day 28 (+/- 2 days) after initial presentation.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of left ventricular global longitudinal strain (GLS) after presentation with ACS/CCS/CLI	Echocardiographical strain analysis will be performed at the below mentioned time points.	Echocardiography will be performed within 24 hours of presentation to the clinic and at day 28 (+/- 2 days) after initial presentation.
Change of inflammatory profile (CRP, PCT, Interleukin panel) after presentation with ACS/CCS/CLI	Blood samples are collected at the below mentioned time points.	Sampling will be performed within 24 hours of presentation to the clinic and at day 28 (+/- 2 days) after initial presentation.
Change of blood pressure after presentation with ACS/CCS/CLI	Blood pressure will be measured at the below mentioned time points.	Blood pressure measurements will be performed within 24 hours of presentation to the clinic and at day 28 (+/- 2 days) after initial presentation.
Change of pulse wave velocity (PWV) after presentation with ACS/CCS/CLI	PWV will be measured at the below mentioned time points.	PWV measurements will be performed within 24 hours of presentation to the clinic and at day 28 (+/- 2 days) after initial presentation.
Change in nitrite metabolism after presentation of ACS/CCS/CLI	Nitrite metabolism will be assed by chemiluminescence detection (CLD).	Nitrite metabolism will be performed within 24 hours of presentation to the clinic and at day 28 (+/- 2 days) after initial presentation.

Collaborators and Investigators

• Sponsor: University Hospital, Essen
• Investigators: Principal Investigator: Christos Rammos, Prof. Dr., University Clinic Essen

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2022
• Primary Completion (Actual): February 1, 2024
• Study Completion (Actual): April 1, 2024

Study Registration Dates

• First Submitted: June 30, 2022
• First Submitted That Met QC Criteria: July 9, 2022
• First Posted (Actual): July 13, 2022

Study Record Updates

• Last Update Posted (Actual): September 24, 2024
• Last Update Submitted That Met QC Criteria: September 22, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Disease Attributes; Atherosclerosis; Coronary Disease; Chronic Disease; Myocardial Infarction; Infarction; Coronary Artery Disease; Peripheral Arterial Disease; Peripheral Vascular Diseases; Infections; Communicable Diseases; Acute Coronary Syndrome; Chronic Limb-Threatening Ischemia
• Other Study ID Numbers: MIAMI Trial

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No