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Key Event: 2236

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Cardiac Heart Failure

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Organ

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
C6R-Derived Protein K7 following Monkeypox infection leads to heart failure	AdverseOutcome	Arthur Author (send email)	Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Term	Scientific Term	Evidence	Link
mammals	mammals	Moderate	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
Adult, reproductively mature	Moderate
Old Age	High

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Mixed	High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Cardiac heart failure is a condition which occurs when the heart is unable to pump blood to meet the body's requirements. As the heart's function weakens due to coronary artery disease and hypertension to heart valve problems, cardiomyopathy, congenital defects, and myocarditis, this will affect its efficiency to achieve its purpose. (Malik et al., 2023). The primary treatment focuses on managing symptoms, improving heart function, and addressing underlying conditions through medications, lifestyle changes, and sometimes surgical procedures. (Sapna et al., 2023).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

In order to measure for cardiac heart failure, there are several techniques which assist in evaluating the heart's function and structure. Clinical assessment and physical examinations are conducted in order to determine if there are abnormal heart sounds or fluid retention. (Ashley et al., 2004). Depending on these results, doctors are able to determine the condition's severity and impact on the body.

Monitoring heart failure can be done through imaging techniques. These techniques include an echocardiography which is used to determine the heart's size, shape, and function. (Omerovic et al., 2023). Another heart imaging technique is the cardiac MRI which is able to take images of the heart's tissues and blood flow to determine areas of damage or scarring. (Lorraine et al., 2017). Another way to indicate heart failure is through the use of biomarkers. Some of the most common biomarkers like B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) can be utilized to beasure the hearts sterss levels through blood tests. (Cao et al., 2019). By using these methods, doctors are able to gain a better understnading of the risk and severity of the heart failure and provide the appropriate treatment.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

Taxonomic:

Taxonomic applicability in mammals for heart failure primarily focuses on their physiological similarities to humans. This will allow them to become models for studying cardiovascular diseases. (Arnolda et al., 1999). Studies including rodents determine specific molecular pathways involved in heart failure. (Ponzoni et al., 2023). Domesticated mammals such as dogs and cats can also naturally develop heart failure akin to humans which provides information on disease progression in a controlled environment. (National Research Council (US) and Institute of Medicine (US) Committee on the Use of Laboratory Animals in Biomedical and Behavioral Research, 1988).

Life stage:

Because applications of cardiac heart failure typically occur later stages of life, changes in physiological structures can occur. In older adults, hypertension and coronary artery disease are the main concerns because of changes due to age. (Madhavan et al., 2018). Middle-aged adults may also experience heart failure due to issues which include diabetes or obesity. (Oktay et al., 2023).

Sex:

The KE is plausibly applicable to both sexes. While it is applicable to both sexes, males develop heart failure at a younger age are more likely to have coronary artery disease. In contrast, females may experience heart failure later in life due to hypertension. (Mosca et al., 2011). Hormonal differences such as estrogen can provide protective effects on the cardiovascular system. (Knowlton et al., 2012).

Regulatory Significance of the Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

Maintaining healthy cardiac health such as long term and sustainable lifestyle is an accepted regulatory goal to reduce the risk of heart failure. This will lead to the development of drug approvals, healthcare policies, and clinical guidelines. Its regulatory significance tries to prioritize the improvmement of the quality of life for individuals affected by heart failure.

References

List of the literature that was cited for this KE description. More help

Arnolda, L. F., Llewellyn-Smith, I. J., & Minson, J. B. (1999). Animal models of heart failure. Australian and New Zealand Journal of Medicine, 29(3), 403–409. https://doi.org/10.1111/J.1445-5994.1999.TB00735.X

Ashley, E. A., & Niebauer, J. (2004). Cardiovascular examination. https://www.ncbi.nlm.nih.gov/books/NBK2213/

Cao, Z., Jia, Y., & Zhu, B. (2019). BNP and NT-proBNP as Diagnostic Biomarkers for Cardiac Dysfunction in Both Clinical and Forensic Medicine. International Journal of Molecular Sciences, 20(8). https://doi.org/10.3390/IJMS20081820

Knowlton, A. A., & Lee, A. R. (2012). Estrogen and the Cardiovascular System. Pharmacology & Therapeutics, 135(1), 54. https://doi.org/10.1016/J.PHARMTHERA.2012.03.007

Lorraine, B., & Lott, C. (2017). MRI Heart (Cardiac MRI) - InsideRadiology. https://www.insideradiology.com.au/cardiac-mri/

Madhavan, M. v., Gersh, B. J., Alexander, K. P., Granger, C. B., & Stone, G. W. (2018). Coronary Artery Disease in Patients ≥80 Years of Age. Journal of the American College of Cardiology, 71(18), 2015–2040. https://doi.org/10.1016/J.JACC.2017.12.068

Malik, A., Brito, D., Vaqar, S., & Chhabra, L. (2023). Congestive Heart Failure. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK430873/

Mosca, L., Barrett-Connor, E., & Kass Wenger, N. (2011). Sex/Gender Differences in Cardiovascular Disease Prevention What a Difference a Decade Makes. Circulation, 124(19), 2145. https://doi.org/10.1161/CIRCULATIONAHA.110.968792

Oktay, A. A., Paul, T. K., Koch, C. A., & Lavie, C. J. (2023). Diabetes, Cardiomyopathy, and Heart Failure. Endotext. https://www.ncbi.nlm.nih.gov/books/NBK560257/

Omerovic, S., & Jain, A. (2023). Echocardiogram. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK558940/

Ponzoni, M., Coles, J. G., & Maynes, J. T. (2023). Rodent Models of Dilated Cardiomyopathy and Heart Failure for Translational Investigations and Therapeutic Discovery. International Journal of Molecular Sciences, 24(4). https://doi.org/10.3390/IJMS24043162

Research, N. R. C. (US) and I. of M. (US) C. on the U. of L. A. in B. and B. (1988). Benefits Derived from the Use of Animals. https://www.ncbi.nlm.nih.gov/books/NBK218274/

Sapna, F., Raveena, F., Chandio, M., Bai, K., Sayyar, M., Varrassi, G., Khatri, M., Kumar, S., & Mohamad, T. (2023). Advancements in Heart Failure Management: A Comprehensive Narrative Review of Emerging Therapies. Cureus, 15(10). https://doi.org/10.7759/CUREUS.46486