An observational study in Heart Failure, Fatigue; Muscle, Heart and Myocardial Dysfunction, sponsored by University Hospitals Coventry and Warwickshire NHS Trust. Recruiting at 1 site in United Kingdom. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2024-06-18.
Sponsored by University Hospitals Coventry and Warwickshire NHS Trust · Observational
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.
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).
6,331 studies on the registry are indexed under Heart Failure; 1,396 are open to participants now.
This study's planned enrollment of 100 is below the median of 200 across 1,983 observational studies indexed under Heart Failure.
Browse Heart Failure studies →University Hospitals Coventry and Warwickshire NHS Trust is the lead sponsor of 57 studies on the registry; 8 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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 donor hearts from deceased individuals that are not transplantable due to technical reasons
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.
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
Time frame: 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
Time frame: 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.
Time frame: Within a day for each experiment
Changes in the phosphorylation potential
This will be calculated by determining the above concentration of adenosine triphosphate and its metabolic by-product including inorganic phosphate, at different times of the contraction fatigue protocol (e.g. before, during, and after).
Time frame: Within a day for each experiment
Changes in the phosphocreatine/ATP ratio
This will be calculated by determining the above concentration of phosphocreatine and ATP at different times of the contraction fatigue protocol (e.g. before, during and after).
Time frame: Within a day for each experiment
Plan to share: Undecided
Started Aug 2021 (actual). Primary completion is estimated for Apr 2025, 44 months after the start.
Of 793 non-industry observational studies under Heart Failure, half reached primary completion within 45 months of starting (the median), counting those still running; a quarter within 23 and three quarters within 99. This study's planned 44 months is close to that.
Counting every sponsor, half of 975 studies reached it within 41 months; a quarter within 23 and three quarters within 89.
How these figures are worked out, and which studies are left out of them.
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University Hospitals Coventry and Warwickshire NHS Trust