Layout 1 Cardiac wasting is not cardiac cachexia: the problem of the subjective/objective genitive in matters of the heart Eur J Transl Myol 35 (3) 14147, 2025 doi: 10.4081/ejtm.2025.14147 Tessitore, Costelli et al. were among the first to report a previously unnoticed loss of heart mass in cachectic mice suffering from a severe tumor burden.1 At the time both the general consensus definition of cachexia2 and the cancer cachexia classification3 did not exist. In particular, cancer cachexia is a syndrome characterized by muscle wasting leading to body weight loss in the presence of cancer.3-5 More recently, Zhou et al. highlighted once more the existence of a tumor-induced loss of heart mass in a murine model of cancer cachexia.6 This study generated a new line of research aimed at exploring the mechanisms underlying cardiac wasting in the presence of cancer. Cardiac wasting in the presence of cancer-induced cachexia is distinct from and other than cardiac cachexia, i.e. the atrophy of skeletal muscle induced by cardiac pathologies.7 To add insult to injury, some authors use the expression “muscle cachexia” meaning muscle atrophy,8 which, as a consequence, may suggest to naive readers that cardiac cachexia is a form of cardiac muscle atrophy. We aim here to clarify the terminology describing these conditions, so as to avoid the misleading use of related expressions: cardiac atrophy and cardiac cachexia may sound alike but are very different. In particular, it is the expression “cardiac cachexia” that raises a problem of ambiguity and should be handled with care. The age-old problem of the subjective/objective genitive case Does the Latin expression timor barbarorum – literally, the fear of barbarians – mean the fear the ancient Romans had of barbarians or the one barbarians had of Romans? Only the context helps one to distinguish between the two options, since the genitive case in Latin can express either. Albeit English differentiates the two options through syntax - with the Saxon genitive or through the order of words - disambiguation remains difficult sometimes. To use a dramatically contemporary example in English, what does “foreigner hating” mean? The fact that we hate foreigners or that foreigners hate us? Due to the use of the expression “muscle cachexia” introduced by some authors to wrongly denote muscle atrophy - 66 papers in PubMed – the compound “cardiac cachexia” may also give rise to the problem of the subjective/objective genitive: does it mean cachexia induced by cardiac problems or atrophy of the cardiac muscle induced by cachexia? Unquestioningly not the latter. The use of “cardiac cachexia” to indicate cardiac atrophy is incorrect. What, then, is cardiac cachexia? More than 400 papers to date refer to cardiac cachexia as a syndrome of skeletal muscle wasting associated to a specific pathology, i.e. Chronic Heart Failure (CHF). Indeed, cardiac cachexia refers to the fact that skeletal muscle, and not cardiac muscle, is dismantled in CHF- induced cachexia. Following the discovery that cardiac wasting also exists in cachexia,6 it appears that the heart can be both the trigger and the target of cachexia. We are concerned that the use of the expression “cardiac cachexia” may be mistakenly used in both its subjective and objective senses. Different options to indicate cardiac wasting: PROs and CONs As stated above, cardiac muscle wasting is not cardiac cachexia. The following are alternative ways to refer to the phenomenon of cardiac wasting: i) atrophy of the heart: this Key Words: cardiac cachexia; cancer cachexia; atrophy of the heart; cardiac atrophy; muscle wasting. Eur J Transl Myol 35 (3) 14147, 2025 doi: 10.4081/ejtm.2025.14147 Cardiac wasting is not cardiac cachexia: the problem of the subjective/objective genitive in matters of the heart Anna Luisa Mazzotti,1 Medhi Hassani,2,3,4,5 Zhenlin Li,2 Denise Paulin,2 Onnik Agbulut,2 Dario Coletti2,3,4 1Assointerpreti, Italian Association of Conference Interpreters, Rome, Italy, and MPS Public Speaking Rome, Italy; 2Sorbonne Université, Institut de Biologie Paris-Seine (IBPS), UMR CNRS 8263, INSERM U1345, Development, Adaptation and Ageing, Paris, France; 3Unit of Histology and Medical Embryology, Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy; 4Interuniversity Institute of Myology, Rome, Italy; 5Université de Brest, Brest, France. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (CC BY-NC 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. - 339 - Cardiac wasting is not cardiac cachexia: the problem of the subjective/objective genitive in matters of the heart Eur J Transl Myol 35 (3) 14147, 2025 doi: 10.4081/ejtm.2025.14147 expression is unambiguous, even though relatively long; it is very general and requires the need to clarify the context in which the atrophy arises, e.g. cancer-induced atrophy of the heart to specify that the trigger is cancer; ii) heart atrophy, which is synonymous with atrophy of the heart and is equally generic; iii) cardiac atrophy, which means atrophy of the heart but sounds dangerously similar to cardiac cachexia; iv) cachectic heart, a more holistic expression not often used to date; v) cardiac wasting, which suggests a pathological condition and is a specific, easily discernible expression, being, therefore, our favorite. Highlighting cardiac wasting in the definition of cachexia The current consensus definition of cachexia2 does not explicitly refer to the loss of cardiac muscle. We think it is appropriate to bear well in mind that both skeletal and cardiac musculature are involved when reporting muscle wasting in cachexia. Cardiac wasting in cachexia leads to heart dysfunction, which ultimately increases the risk of death of cachectic patients due to cardiovascular complications. List of abbreviations CHF, Chronic Heart Failure Contributions All authors were involved in drafting the manuscript and in its critical revision. All authors read and approved the final manuscript. Funding DC is funded by Progetti di Ateneo Medi 2019 and 2024 Sapienza. Conflict of interest The authors declare no competing interests. Ethics approval Not applicable. Corresponding author Dario Coletti, Istologia, Via A. Scarpa 16 00161 Rome, Italy. Tel.: +39.0649766756. ORCID ID: 0000-0001-7373-1953 E-mail: dario.coletti@uniroma1.it Co-authors Anna Luisa Mazzotti N/A E-mail: mazzottiannalu@gmail.com Medhi Hassani ORCID ID: 0000-0001-6498-1344 E-mail: medhihsn@gmail.com Zhenlin Li ORCID ID: 0000-0002-3706-4505 E-mail: zhenlin.li@sorbonne-universite.fr Denise Paulin ORCID ID: 0000-0003-4612-7931 E-mail: denise.paulin@orange.fr Onnik Agbulut ORCID ID: 0000-0003-1923-8871 E-mail: onnik.agbulut@sorbonne-universite.fr References 1 Tessitore L, Costelli P, Bonetti G, Baccino FM. Cancer cachexia, malnutrition, and tissue protein turnover in experimental animals. Arch Biochem Biophys 1993; 306:52-8. 2 Evans WJ, Morley JE, Argilés J, et al. Cachexia: a new definition. Clin Nutr 2008;27:793-9. 3 Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011;12:489-95. 4 Benoni A, Renzini A, Cavioli G, Adamo S. Neurohypophyseal hormones and skeletal muscle: a tale of two faces. Eur J Transl Myol 2020;30:8899. 5 Scicchitano BM, Bouchè M, Nervi C, Coletti D. A tribute to Professor Sergio Adamo, Full Professor of Histology and Embryology at Sapienza University, Rome. Eur J Transl Myol 2022; 32:10434. 6 Zhou X, Wang JL, Lu J, et al. Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival. Cell 2010;142:531-43. 7 Loncar G, Springer J, Anker M, et al. Cardiac cachexia: hic et nunc. J Cachexia Sarcopenia Muscle 2016;7:246- 60. 8 Mitch WE, Price SR. Transcription factors and muscle cachexia: is there a therapeutic target? Lancet 2001; 357:734-5. Disclaimer All claims expressed in this article are solely those of the authors and do not necessarily represent those of their af- filiated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Submitted: 16 July 2025. Accepted: 18 July 2025. Early access: 2 September 2025. - 340 - mailto:mazzottiannalu@gmail.com mailto:medhihsn@gmail.com mailto:zhenlin.li@sorbonne-universite.fr mailto:denise.paulin@orange.fr mailto:onnik.agbulut@sorbonne-universite.fr