Metabolic Characterization of Patients With Dilated Cardiomyopathy (MECHAD)

Metabolic Characterization of Patients With Dilated Cardiomyopathy a Prospective Case-control Study

The overall aim of the study is to explore the energy metabolism of the failing heart.

Primary objective is to understand the differences in the energy metabolism in patients with DCM and heart failure compared to matched controls without heart failure. Secondary objectives, is to understand if optimal medical therapy, including sodium-gucose transporter 2 inhibitors (SGLT2i), alter the cardiac metabolism in DCM-patients. The investigators will also examine if changes in cardiac metabolism happens during exercise in patients with DCM.

This will be done with invasive measurements of a range of energy substrate metabolites in the coronary sinus of the heart in patients with heart failure due to DCM and controls without heart failure respectively. A range of other clinical characteristics will also be examined to characterize patients and controls.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; DCM - Dilated Cardiomyopathy
• Intervention / Treatment: Diagnostic test: Right hearted catheterization

Detailed Description

Study Design:

The MECHAD study is an explorative prospective cohort study with matched controls including patients with heart failure with reduced ejection fraction (HFrEF, EF≤40%) due to DCM in NYHA-class II-IV, ≥18 years, referred to Department of Cardiology/Sahlgrenska for heart failure work-up. A control group will be collected with age, gender and body mass index (BMI) matched controls without heart failure from the electrophysiology laboratory.

Study Site:

Sahlgrenska University Hospital is a tertiary center for patients in the need of heart failure evaluation, staging and therapy. Further, Sahlgrenska University Hospital is included in the assignment as one of the national centers for heart transplantation in Sweden. Patients with advanced HF are referred from the western and northern parts of Sweden and as part of clinical evaluation they most often undergo transthoracic echocardiogram (TTE), cardiopulmonary exercise test (CPET) as well as right-sided heart catheterization (RHC) with biopsy from the right ventricle septum or the lateral wall in the left ventricle. The site receives approximately 150 patients for evaluation every year and about 70% have clinically DCM.

Patient information and consent:

The Principal Investigator (or delegated sub investigator) will provide each patient with verbal and written information regarding the objectives and procedures of the study and possible risks involved. The patients will be informed about their right to withdraw from the study at any time. Prior to any study related procedures, the informed consent will be reviewed, signed and dated by the patient and investigator. The research unit at the Department of Cardiology/Sahlgrenska University hospital have dedicated research nurses who will facilitate coordination of the study.

Study timetable:

The inclusion in the study is planned to start in Q1 2022 and will continue until 30 patients with HF and 60 patients without HF (controls) are included. The investigators estimate to be able to include one patient per week in average.

Power Calculation and statistical analyses The investigators aim to include 30 patients with HF and 60 matched patients without HF as controls. To calculate the power, data was used from one study in humans showing an increase in 3-hydroxybutanoyl from 0.29 pmol/mg in a non-failing heart to 0.59 pmol/mg in failing heart. This large difference would result in only 2 patients in each group. However, the estimated increase in 3-hydroxybutanoyl does not directly transmitted to our cohort of DCM, therefore a larger sample was chosen.

• Study Type: Observational
• Enrollment (Anticipated): 90

Contacts and Locations

• Study Contact: Name: Maria Wideqvist; Phone Number: +46313434416; Email: maria.wideqvist@vgregion.se

Study Locations

• Sweden
  • Western Sweden
    • Gothenburg, Western Sweden, Sweden, 41345
      • Recruiting
      • Sahlgrenska University Hospital
      • Contact: Maria Wideqvist, MD; Phone Number: +46313434416; Email: maria.wideqvist@vgregion.se

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Sahlgrenska University Hospital is a tertiary center for patients in the need of heart failure evaluation. Further, Sahlgrenska University Hospital is included in the assignment as one of the national centers for heart transplantation in Sweden. Patients with advanced HF are referred from the western and northern part of Sweden and as part of clinical evaluation they most often undergo transthoracic echocardiogram (TTE), cardiopulmonary exercise test (CPET) and right-sided heart catheterization (RHC) with myocardial biopsy. The site receives approximately 150 patients for evaluation every year and about 70% have clinically DCM. The study population will be will be recruited from this population.

The control population of the study will be recruited from the electrophysiology laboratory.

Description

For cases (Heart Failure on the basis of DCM)

Inclusion Criteria:

• Signed and dated the Informed Consent Form
• Male and female subjects ≥18 years of age
• Chronic Heart failure (HF) with LVEF ≤40%
• HF due to dilated cardiomyopathy (DCM)
• New York Heart Association (NYHA) class ≥2
• Treatment with basic optimal medical therapy.
• Clinical indication for invasive evaluation of heart failure

Exclusion Criteria:

• Life expectancy < 3 years due to other reasons than cardiovascular, cardiac transplantation or left ventricular assist device
• Diabetes mellitus type 1 and 2
• Known hereditary hypercholesterolemia
• Ongoing lipid lowering therapy
• Patients on ketogenic diets
• BMI>35 or <19
• Pregnancy
• Any current life-threatening cardiac dysrhythmia, cardiac surgery, acute coronary syndrome, or non-elective percutaneous coronary intervention (PCI) <3 months
• Current significant major or unstable respiratory disease
• Considerable hematological disease, hepatic disease, renal disease and/or gastrointestinal disease
• Stroke, transient ischemic attack, carotid surgery or angioplasty <3months
• estimated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI formula) <30 mL/min/1.73m2 or patients on renal dialysis
• Expected inability (by the investigator) to comply with the protocol
• Subjects incapable to giving consent personally

For control subjects (no heart failure)

Inclusion criteria:

• Signed and dated Informed Consent Form
• Male and female subjects ≥18 years of age
• Clinical indication for electrophysiology examination

Exclusion criteria:

• Heart Failure (HFpEF, heart failure with mid-range ejection fraction (HFmrEF) or HFrEF)
• Life expectancy < 3 years due to other reasons than cardiovascular, cardiac transplantation or left ventricular assist device
• Diabetes mellitus type 1 and 2
• Known hereditary hypercholesterolemia
• Ongoing lipid lowering therapy
• Patients on ketogenic diets
• BMI>35 or <19
• Pregnancy
• Any current life-threatening cardiac dysrhythmia, cardiac surgery, acute coronary syndrome, or non-elective PCI <3 months
• Current significant major or unstable respiratory disease
• Considerable hematological disease, hepatic disease, renal disease and/or gastrointestinal disease
• Stroke, transient ischemic attack, carotid surgery or angioplasty <3months,
• eGFR by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI formula) <30 mL/min/1.73m2 or patients on renal dialysis
• Expected inability (by the investigator) to comply with the protocol
• Subjects incapable to giving consent personally

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Dilated cardiomyopathy; Patients with heart failure on the basis of dilated cardiomyopathy.	Diagnostic test: Right hearted catheterization; Right hearted catheterization and collection of blood sampels in the coronary sinus, arterial blood and central venous blood for analysis of energy substrate metabolites.
Control group without heart failure; Control group from the ablation laboratory without heart failure	Diagnostic test: Right hearted catheterization; Right hearted catheterization and collection of blood sampels in the coronary sinus, arterial blood and central venous blood for analysis of energy substrate metabolites.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic markers	Energy substrate metabolic markers in arterial blood and coronary sinus for the calculation of energy metabolism in the myocardium.	through study completion, on average 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic markers after medical optimization	Energy substrate metabolic markers in arterial blood and coronary sinus for the calculation of energy metabolism in the myocardium.	through study completion, on average 4 years

Collaborators and Investigators

• Sponsor: Göteborg University
• Collaborators: Sahlgrenska University Hospital, Sweden
• Investigators: Principal Investigator: Charlotta Ljungman, Sahlgrenska University Hospital, Sweden

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): January 1, 2026

Study Registration Dates

• First Submitted: November 19, 2021
• First Submitted That Met QC Criteria: March 8, 2022
• First Posted (Actual): March 17, 2022

Study Record Updates

• Last Update Posted (Actual): March 17, 2022
• Last Update Submitted That Met QC Criteria: March 8, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Energy metabolism
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Cardiomegaly; Laminopathies; Cardiomyopathies; Cardiomyopathy, Dilated
• Other Study ID Numbers: MECHAD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No