POWER Myocardial Fatigue Study: a Biomechanical Assessment of Contractility of Human Myocardium

NCT04899635 | Recruiting

• 1 other identifier: PB528721
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

To gain a comprehensive understanding of the biomechanical behaviour of human heart to explore the concept of myocardial fatigue in response to a temporal range of preload, afterload and drug-induced inotropy using in-vitro contractile assays.

Conditions

Heart Failure; Fatigue; Muscle, Heart; Myocardial Dysfunction; Exhaustion; Heart

Keywords

Myocardial Fatigue; Preload; Afterload; Cardiac Work-loop; Cardiomyocytes; Biomechanical model

Outcome Measures

Primary Outcomes (3)

• Changes in the force generated by the muscle cell and/or muscle slice

  This will be based on the effects of changing load and/or exposure to drug-induced inotropic effects

  Within a day for each experiment

• Changes in the velocity of shortening by the muscle cell and/or muscle slice

  This will be based on the effects of changing load and/or exposure to drug-induced inotropic effects

  Within a day for each experiment

• Changes in the end-systolic force-length relationship of the muscle cell and/or muscle slice

  This will be based on the effects of changing load and/or exposure to drug-induced inotropic effects, and calculated by integrating the above force and length changes.

  Within a day for each experiment

Secondary Outcomes (2)

• Changes in the phosphorylation potential

  Within a day for each experiment

• Changes in the phosphocreatine/ATP ratio

  Within a day for each experiment

Study Arms (2)

Diseased cardiac tissue

Heart muscle or cells (cardiomyocytes) will be obtained from patients undergoing cardiac surgery, namely coronary artery bypass grafting or for severe valvular heart disease.

Other: In-vitro contractile fatigue protocol

Healthy cardiac tissue

Healthy donor hearts from deceased individuals that are not transplantable due to technical reasons

Other: In-vitro contractile fatigue protocol

Interventions

In-vitro contractile fatigue protocol OTHER

Using contractility assays for muscle slices or the work-loop assay for isolated heart cells, the tissue preparation will undergo a series of contraction and relaxation under varying levels of preload, afterload, stimulation frequency and under other experimental conditions such as drug-induced inotropism.

Diseased cardiac tissue; Healthy cardiac tissue

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Human cardiac tissues (atrial appendages and ventricular tissue biopsies) are obtained from patients undergoing elective or inpatient open-heart surgery, namely coronary artery bypass grafting and valvular replacement. If available, explanted failing hearts are also recruited for experimentation. A control population consists of healthy donor hearts that are deemed non-transplantable and collected by the Arden Tissue Bank at UHCW.

You may qualify if:

• All adult patients between 18 to 85-years old undergoing open-heart surgery who can undergo the consent process for the study
• Healthy donor hearts that are deemed non-transplantable and consent received from a legal representative

You may not qualify if:

• This criterion is kept to a minimum since the availability of human myocardial samples is finite and dependent on the limited number of patients undergoing cardiac surgery annually within the local hospital.
• Patients who do not have the mental capacity to undergo the consent process
• For the safety of researchers, patients with evidence of ongoing blood-borne infections such as HIV, or a recent positive test for COVID-19 (within 10 days of last PCR test).

Sponsors & Collaborators

• University Hospitals Coventry and Warwickshire NHS Trust: lead
• Coventry University: collaborator

Study Sites (1)

University Hospitals Coventry and Warwickshire

Coventry, CV22DX, United Kingdom

RECRUITING

Related Publications (2)

• Tran P, Joshi M, Banerjee P. Concept of myocardial fatigue in reversible severe left ventricular systolic dysfunction from afterload mismatch: a case series. Eur Heart J Case Rep. 2021 Mar 7;5(3):ytab089. doi: 10.1093/ehjcr/ytab089. eCollection 2021 Mar.

  PMID: 34113768 BACKGROUND

• Banerjee P. Heart failure: a story of damage, fatigue and injury? Open Heart. 2017 Oct 15;4(2):e000684. doi: 10.1136/openhrt-2017-000684. eCollection 2017.

  PMID: 29081980 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Fatigue

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Patrick Tran

CONTACT

02476964000; patricktranphd@gmail.com

Patrick Tran

CONTACT

+442476965689; patrick.tran2@uhcw.nhs.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2021
• First Posted: May 24, 2021
• Study Start: August 3, 2021
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: June 18, 2024

Record last verified: 2024-06

Locations

GB (1)