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

NCT ID: NCT04899635

Last Updated: 2024-06-18

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-08-03
• Study Completion Date: 2025-04-30

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.

Detailed Description

A continuum of pathological states from fatigue, injury to damage of the myocardium has been proposed which complements the continuous spectrum of HF and reconciles the seemingly disparate plethora of mechanisms behind the pathophysiology of HF. Unlike skeletal muscle where mechanical stress can be readily removed upon fatigue, an impaired left ventricle continues to receive preload from the right ventricle and cannot rest, maintaining cardiac output only at the expense of increasing filling pressures (as in HF with preserved ejection fraction). If concurrently faced with high afterload from vascular stiffness, ventricular-arterial decoupling occurs, driving mechanical inefficiency and diminishing cardiac output (as in HF with reduced ejection fraction). Chances of recovery is linked to the degree of fatigue, cardiomyocyte loss and replacement with non-contractile fibrosis. Assuming that the myocardium is in a state of chronic fatigue before reaching advanced stages of fibrosis, cases such as aortic stenosis or hypertensive heart disease may potentially be reversible if the pathological load is promptly removed.

This study will be re-synthesizing existing knowledge of the biomechanical behaviour of healthy and diseased cardiac myocytes and muscle in a new light of the theoretical constructs of myocardial fatigue, aligned with the existing energy-starvation theory. It will be a proof-of-concept study. Just as Frank-Starling's relationship between preload and cardiac output emerged from pre-clinical studies on muscle behaviour with subsequently major clinical implications, this study represents a necessary stepping stone to adding a new layer of insight into the pathophysiology of heart failure (HF).

Conditions

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

In-vitro contractile fatigue protocol

Intervention Type: 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.

Healthy cardiac tissue

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

In-vitro contractile fatigue protocol

Intervention Type: 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.

Interventions

In-vitro contractile fatigue protocol

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Coventry University

OTHER

Sponsor Role: collaborator

University Hospitals Coventry and Warwickshire NHS Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Hospitals Coventry and Warwickshire

Coventry, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Patrick Tran

Role: CONTACT

patricktranphd@gmail.com

02476964000

Patrick Tran

Role: CONTACT

patrick.tran2@uhcw.nhs.uk

+442476965689

Facility Contacts

Ceri Jones

Role: primary

References

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.

Reference Type: BACKGROUND

PMID: 34113768 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29081980 (View on PubMed)

Other Identifiers

PB528721

Identifier Type: -

Identifier Source: org_study_id