TYPE Editorial PUBLISHED 28 February 2023 DOI 10.3389/fcvm.2023.1141032 Editorial: The role of sex in heart OPEN ACCESS failure and transplantation, volume II EDITED AND REVIEWED BY Matteo Cameli, University of Siena, Italy *CORRESPONDENCE Manuel Martínez-Sellés Ana Ayesta1 , Beatriz Díaz-Molina1 , Antoni Bayes-Genis2 , mmselles@secardiologia.es SPECIALTY SECTION Adrián Baranchuk3 and Manuel Martínez-Sellés4* This article was submitted to 1 Área del Corazón, Servicio de Cardiología, Hospital Universitario Central de Asturias, Oviedo, Spain, Heart Failure and Transplantation, 2 Servicio de Cardiología, Hospital Universitari Germans Trias i Pujol, CIBERCV, Universidad Autónoma de a section of the journal Barcelona, Badalona, Spain, 3 Kingston Health Science Center, Division of Cardiology, Queen’s University, Frontiers in Cardiovascular Medicine Kingston, ON, Canada, 4 Servicio de Cardiología, Hospital General Universitario Gregorio Marañón, RECEIVED 09 January 2023 Centro de Investigación Biomédica en Red. Enfermedad Cardiovascular (CIBERCV), Universidad ACCEPTED 13 February 2023 Europea, Universidad Complutense, Madrid, Spain PUBLISHED 28 February 2023 CITATION KEYWORDS Ayesta A, Díaz-Molina B, Bayes-Genis A, Baranchuk A and Martínez-Sellés M (2023) heart failure, heart transplantation, frailty, sex, women Editorial: The role of sex in heart failure and transplantation, volume II. Front. Cardiovasc. Med. 10:1141032. doi: 10.3389/fcvm.2023.1141032 COPYRIGHT Editorial on the Research Topic © 2023 Ayesta, Díaz-Molina, Bayes-Genis, Baranchuk and Martínez-Sellés. This is an The role of sex in heart failure and transplantation, volume II open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the Heart failure (HF) is one of the main causes of hospitalization and death in developed original author(s) and the copyright owner(s) countries. This is partly due to population aging but also due to increased survival in patients are credited and that the original publication in this journal is cited, in accordance with with heart disease (1). Differences between men and women with HF seem to be extremely accepted academic practice. No use, relevant a several of them are still under investigation. This Research Topic is a continuation distribution or reproduction is permitted which of the first volume previously published regarding this topic. does not comply with these terms. Den Ruijter summarizes the importance of cardiovascular disease in women and the role of sex in this relation. Most cardiovascular diseases at younger ages are more common in men, but under diagnosis in women might increase this difference. X chromosome seems to be related to inflammation and the Y chromosome to atherosclerosis. This fact might be one of the explanations to why men suffer more frequently from coronary artery disease and HF with left ventricular reduced ejection fraction, while women typically have stable atherosclerosis with non-obstructive coronary disease and HF with preserved left ventricular ejection fraction. Women underrepresentation in clinical trials is still an issue that should be solved as sex-dependent mechanisms of cardiovascular diseases might modulate the effect of HF treatments. In fact, Sanromán Guerrero et al. conducted a systematic review of 29 randomized clinical trials in patients with HF with reduced ejection fraction. They observed that the proportion of women was low, there was not a pre-specified analysis of efficacy by sex, and the quality of evidence on the efficacy of medical treatment and devices in women was poor. Dahlen et al. described a sex-specific association between parathyroid hormone and platelet indices in HF patients. The phenotypes of symptomatic HF varied depending on the interaction between parathyroid hormone and platelets in men and women. In women with symptomatic HF with reduced ejection fraction there was a positive association between parathyroid hormone and mean platelet volume, while platelet count was inversely associated with parathyroid hormone in males with HF with reduced ejection fraction and in both sexes with HF with preserved ejection fraction. Frontiers in Cardiovascular Medicine 01 frontiersin.org Ayesta et al. 10.3389/fcvm.2023.1141032 Some treatments may precipitate HF in women. Cheng et al. women. They found that, compared to males, females had worse evaluated the risk of HF hospitalizations in patients suffering from cardiac diastolic function, worse New York Heart Association gout under febuxostat and allopurinol. Febuxostat users had a functional class and worse quality of life. However, outcomes higher risk of HF hospitalization than allopurinol users, irrespective in women were better than in men, with lower cardiovascular of previous cardiovascular risk. Interestingly, the risk was higher in and all-cause mortality and less hospitalization due to HF. They women than in men. found no association between sex and spironolactone effects. Díez- Bi et al. analyzed the effect of sex on left atrial remodeling Villanueva et al. present a post-hoc analysis of 499 outpatients (28% and its relationship with myocardial fibrosis in 85 patients with women) with HF older than 75 years included in the FRAGIC hypertrophic obstructive cardiomyopathy treated with surgical registry (impacto de la FRAGilidad y otros síndromes Geriátricos septal myectomy. Left atrial function was evaluated using the early en el manejo clínico y pronóstico del paciente anciano ambulatorio atrial peak of emptying rate and was normalized by left ventricular con Insuficiencia Cardíaca) (3). Compared to men, women were filling volume. These measurements were lower in patients with more frail and had more frequently other geriatric syndromes, as this entity compared with healthy controls, particularly in the case malnutrition, depression and poorer physical status. Interestingly, of female patients. This was attributed to a higher susceptibility this was the case even despite the lower rates of comorbidities in to myocardial fibrosis in women, quantified by collagen volume women than in men. Frailty was less common in men but was only fraction on magnetic cardiac resonance imaging. These would an independent predictor of mortality in males. explain some previously evidence that suggests more severe We would like to finish this Research Topic with a call for action diastolic dysfunction in women than in men. Gual-Capllonch to perform more studies on different aspects of HF in women and et al. review sex differences in the prevalence of atrial mitral and men. It is particularly important to address this issue in elderly tricuspid regurgitations. These valvular heart diseases occur mainly patients with HF, as both women and advanced aged patients have in patients with atrial fibrillation and HF with preserved ejection been traditionally underrepresented in HF studies. fraction. Women have a higher prevalence than men, especially in the case of atrial tricuspid regurgitation. Several potential mechanisms might explain these differences. Sex hormones may Author contributions induce a proinflammatory state with different electrophysiological responses leading to a more advanced left atrial dysfunction and AA prepared the first draft of the manuscript. BD-M, fibrosis in women. In addition, histopathological differences in the AB-G, AB, and MM-S improved the manuscript with relevant annuli and leaflets between women and men have been described. content, contributed to the article, and approved the submitted Finally, a later diagnosis of atrial fibrillation and of HF with version. All authors contributed to the article and approved the preserved ejection fraction in women may lead to a less aggressive submitted version. treatment increasing the prevalence of atrial mitral and tricuspid regurgitation in females. Lozano-Jiménez et al. describe a cohort of 163 patients Conflict of interest presenting with cardiogenic shock, 39 women (24%). Postcardiotomy and fulminant myocarditis were more frequent The authors declare that the research was conducted in the in women, while acute myocardial infarction was more common absence of any commercial or financial relationships that could be in male. The use of temporary mechanical circulatory support construed as a potential conflict of interest. and its escalation was similar in women and men. The authors found no relevant sex-differences in hospital mortality, Society for Cardiovascular Angiography and Interventions risk stratification, Publisher’s note and in the use of advanced HF therapies. Two manuscripts focused on sex-differences in older patients All claims expressed in this article are solely those of the with HF. Sun et al. presented a secondary analysis of The Treatment authors and do not necessarily represent those of their affiliated of Preserved Cardiac Function Heart Failure with an Aldosterone organizations, or those of the publisher, the editors and the Antagonist Trial (TOPCAT) study (2) evaluating the impact of reviewers. Any product that may be evaluated in this article, or sex on baseline characteristics and outcomes of 1,619 patients claim that may be made by its manufacturer, is not guaranteed or with preserved ejection fraction older than 70 years, with 55.1% endorsed by the publisher. References 1. Emmons-Bell S, Johnson C, Roth G. Prevalence, incidence and fraction. N Engl J Med. (2014) 370:1383–92. doi: 10.1056/NEJMoa131 survival of heart failure: a systematic review. Heart. (2022) 108:1351– 3731 60. doi: 10.1136/heartjnl-2021-320131 3. Jiménez-Méndez C, Díez-Villanueva P, Bonanad C, Ortiz-Cortés C, Barge- 2. Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett Caballero E, Goirigolzarri J, et al. Frailty and prognosis of older patients with chronic B, et al. Spironolactone for heart failure with preserved ejection heart failure. Rev Esp Cardiol. (2022) 75:1011–19. doi: 10.1016/j.rec.2022.04.016 Frontiers in Cardiovascular Medicine 02 frontiersin.org