NCT04899635

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

Profiling Biomechanical Responses and Workload of the Human Myocardium to Explore the Concept of Myocardial Fatigue and Reversibility

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 100 (estimated)
• Sponsor: University Hospitals Coventry and Warwickshire NHS Trust · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: —

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

Interventions

Type	Name	Description
OTHER	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.

Timeline

• Start date: 2021-08-03
• Primary completion: 2025-04-30
• Completion: 2025-04-30
• First posted: 2021-05-24
• Last updated: 2024-06-18

Locations

1 site across 1 country: United Kingdom