Heart FailurePOWERNCT04899635
POWER Myocardial Fatigue Study: a Biomechanical Assessment of Contractility of Human Myocardium
An observational study of Heart Failure and Fatigue; Muscle, Heart, run by University Hospitals Coventry and Warwickshire NHS Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Heart Failure, Fatigue; Muscle, Heart, Myocardial Dysfunction
- What is being tested?
- In-vitro contractile fatigue protocol
- How many people
- 100 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 3 Aug 2021to 30 Apr 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
University Hospitals Coventry and Warwickshire
Coventry, CV22DX
Ceri Jones
Patrick Tran
About this study
Official title: Profiling Biomechanical Responses and Workload of the Human Myocardium to Explore the Concept of Myocardial Fatigue and Reversibility
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.
Read the 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).
- Being tested
- In-vitro contractile fatigue protocol
- Keywords
- Myocardial Fatigue, Preload, Afterload, Cardiac Work-loop, Cardiomyocytes, Biomechanical model
- Medical subject headings
- Heart Failure, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
In-vitro contractile fatigue protocolOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: In-vitro contractile fatigue protocol | |
| Healthy cardiac tissue | Healthy donor hearts from deceased individuals that are not transplantable due to technical reasons Receives: Other: In-vitro contractile fatigue protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: Within a day for each experiment
Secondary outcomes (2)
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).
Measured: 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).
Measured: Within a day for each experiment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2021
- Study start3 Aug 2021
- Primary completion30 Apr 2025 (estimated)
- Study completion30 Apr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospitals Coventry and Warwickshire NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Coventry University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04899635
- Sponsor's protocol ID
- PB528721
- Acronym
- POWER
- Status last verified
- Jun 2024
- First submitted
- 11 May 2021
- Last updated
- 18 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 34113768Banerjee 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.
PubMed 29081980
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Profiling Biomechanical Responses and Workload of the Human Myocardium to Explore the Concept of Myocardial Fatigue and Reversibility
- ClinicalTrials.gov ID
- NCT04899635
- Acronym / sponsor ID
- POWER / PB528721
- Keywords
- Myocardial Fatigue, Preload, Afterload, Cardiac Work-loop, Cardiomyocytes, Biomechanical model
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Hospitals Coventry and Warwickshire NHS TrustUniversity, hospital or other
- Collaborators
- Coventry University
- Study start
- 3 Aug 2021 (actual)
- Primary completion
- 30 Apr 2025 (estimated)
- Study completion
- 30 Apr 2025 (estimated)
- First posted
- 24 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Diseased cardiac tissue | – | Other: In-vitro contractile fatigue protocolHeart muscle or cells (cardiomyocytes) will be obtained from patients undergoing cardiac surgery, namely coronary artery bypass grafting or for severe valvular heart disease. |
| Healthy cardiac tissue | – | Other: In-vitro contractile fatigue protocolHealthy donor hearts from deceased individuals that are not transplantable due to technical reasons |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (3 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| In-vitro contractile fatigue protocolUsing 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. | Other | Diseased cardiac tissue, Healthy cardiac tissue |
Primary outcome
Changes in the force generated by the muscle cell and/or muscle slice
Time frame: Within a day for each experiment
This will be based on the effects of changing load and/or exposure to drug-induced inotropic effects
Changes in the velocity of shortening by the muscle cell and/or muscle slice
Time frame: Within a day for each experiment
This will be based on the effects of changing load and/or exposure to drug-induced inotropic effects
Changes in the end-systolic force-length relationship of the muscle cell and/or muscle slice
Time frame: Within a day for each experiment
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.
2 secondary outcomes
Changes in the phosphorylation potential
Time frame: Within a day for each experiment
Changes in the phosphocreatine/ATP ratio
Time frame: Within a day for each experiment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2024.
- Background: PubMed 34113768Tran 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.
- Background: PubMed 29081980Banerjee 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Failure and Fatigue; Muscle, Heart, run by University Hospitals Coventry and Warwickshire NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Patrick Tran (02476964000, patricktranphd@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in the force generated by the muscle cell and/or muscle slice (time frame: Within a day for each experiment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04899635, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2024.