EDITORIAL published: 25 May 2021 doi: 10.3389/fcvm.2021.690438 Editorial: The Role of Sex in Heart Failure and Transplantation Manuel Martínez-Sellés 1*, Ana Ayesta 2 , Beatriz Díaz-Molina 2 , Antoni Bayes-Genis 3 and Adrian Baranchuk 4 1 Servicio de Cardiología, Hospital General Universitario Gregorio Marañón, CIBERCV. Universidad Europea, Universidad Complutense, Madrid, Spain, 2 Servicio de Cardiología, Hospital Universitario Central de Asturias, Oviedo, Spain, 3 Servicio de Cardiología, Hospital Universitari Germans Trias i Pujol, CIBERCV, Universidad Autónoma de Barcelona, Badalona, Spain, 4 Kingston Health Science Center, Division of Cardiology, Queen’s University, Kingston, ON, Canada Keywords: heart failure, heart transplantation, sex, prognosis, gender Editorial on the Research Topic The Role of Sex in Heart Failure and Transplantation The epidemic of heart failure (HF) is increasing, mainly due to population aging. As women tend to develop HF at an older age compared to men (1), the prevalence of HF will probably grow at a higher speed in females than in males. Sex-related differences in HF have been described and include epidemiology, etiology, diagnosis, treatment, and prognosis. Unfortunately, women are underrepresented in HF trials and the source of most of these differences is unclear. Women have a better age-adjusted prognosis but survival gains were less in women over the last two decades (2). In addition, women experience worse quality of life during and after HF hospitalization (3). This Research Topic aims to focus on sex-related factors in HF and transplantation. In this special volume, Postigo and Martínez-Sellés showed that women with HF are more likely to be older, hypertensive, present valvular heart disease, and non-ischemic cardiomyopathy Edited and reviewed by: than men. They depicted relevant sex-related differences, including biological mechanisms for Hester Den Ruijter, University Medical Center HF, age, etiology, precipitating factors, comorbidities, left ventricular ejection fraction, treatment Utrecht, Netherlands effects, and prognosis. Women have greater clinical severity of HF, with more symptoms and worse functional class, and receive less guideline-proven therapies than men. In spite of both facts, females *Correspondence: Manuel Martínez-Sellés with HF have better prognosis than males. The authors showed how the reasons for this survival mmselles@secardiologia.es advantage are probably multifactorial but prior pregnancies seem to play a role. López-Vilella et al. describe how female sex confers different prognosis in patients with HF. In 1,291 patients Specialty section: discharged after HF exacerbation, the authors found a trend to better survival in females with This article was submitted to reduced ejection fraction than in males. Yet, women presented more readmissions than men, in Heart Failure and Transplantation, accordance with the previously described greater clinical severity in females. a section of the journal Cediel et al. described sex-related differences in HF biomarkers. Kinetics of biological circulating Frontiers in Cardiovascular Medicine biomarkers are different in women and men but most clinicians do not take sex into account when Received: 02 April 2021 they assess them. Women tend to exhibit higher levels of natriuretic peptides and galectin-3 and Accepted: 04 May 2021 lower levels of cardiac troponins and soluble ST2 than man. Many biological factors explain these Published: 25 May 2021 differences, including body composition, fat distribution, or menopausal status. Citation: Farrero et al. focused on the impact of HF therapies in women. Current HF guidelines Martínez-Sellés M, Ayesta A, recommend drug up-titration to the same target doses in both men and women, but some factors Díaz-Molina B, Bayes-Genis A and may impair achieving this goal in women, among them, more common adverse drug reactions and Baranchuk A (2021) Editorial: The Role of Sex in Heart Failure and lack of evidence regarding the optimal drug dose. Women are less likely than men to receive a Transplantation. cardiac device in clinical practice, although they show better response to cardiac resynchronization Front. Cardiovasc. Med. 8:690438. therapy. Females also receive advanced HF therapies less frequently. Technological advances in doi: 10.3389/fcvm.2021.690438 mechanical circulatory support, with smaller devices, will likely increase their implantation in Frontiers in Cardiovascular Medicine | www.frontiersin.org 1 May 2021 | Volume 8 | Article 690438 Martínez-Sellés et al. Editorial: The Role of Sex in Heart Failure and Transplantation women. Tokodi et al., used a machine learning approach in a author concluded that, when allocating a graft, sex-mismatch registry of 2,191 patients treated with cardiac resynchronization should be considered. therapy. The authors were able to create models that predicted Finally, Sobanski et al. described sex-related differences in all-cause mortality. Interestingly, sex-specific patterns of palliative care for HF patients. Women live longer, and after predictors were identified, and hemoglobin was less important a husband or partner’s death, they suffer from a stronger in females compared to males. Chibber and Baranchuk revised sense of loneliness, are more dependent on institutionalized sex-related differences in catheter ablation for HF patients with care and have more unaddressed needs than men. As the atrial fibrillation. These differences include the referral of fewer prevalence of comorbidities [like diabetes (4) or chronic pain women for catheter ablation, older age of women at ablation, and syndromes] grows with age, women suffer from a higher higher risk of post-ablation recurrence of atrial fibrillation. number of symptoms (such as pain and breathlessness) than García-Cosío et al. focused on sex influence in advanced men. Sex-specific differences have been described in symptom HF therapies and outcome following heart transplantation. pathophysiology, distribution and the required management The authors described how women account for a minority needed for their successful alleviation. of patients on the waiting list for heart transplantation or This Research Topic highlights the importance of studying other advanced HF therapies. However, long-term results sex differences in HF and provide insight on factors that of heart transplants are equal for both men and women. may contribute to future studies regarding the role of sex in Ayesta described the influence of sex-mismatch on prognosis cardiovascular physiology and HF pathophysiology. Further data after heart transplantation. In most studies, donor/recipient may help to improve the diagnosis and management of HF in sex-mismatch has been associated with poor prognosis, women and men. especially in male recipients of female hearts. This is probably related to physiological sex-related differences, differences AUTHOR CONTRIBUTIONS in complications rates after heart transplantation (rejection, cardiovascular allograft vasculopathy, and primary graft failure), All authors listed have made a substantial, direct and intellectual size mismatch, and recipient pulmonary hypertension. The contribution to the work, and approved it for publication. REFERENCES 4. Martínez-Sellés M, Doughty RN, Poppe K, Whalley GA, Earle N, Tribouilloy C, et al. Gender and survival in patients with heart failure: interactions with 1. Martínez-Sellés M, García Robles JA, Prieto L, Domínguez Muñoa diabetes and aetiology. Results from the MAGGIC individual patient meta- M, Frades E, Díaz-Castro O, et al. Systolic dysfunction is a predictor analysis. Eur J Heart Fail. (2012) 14:473–9 doi: 10.1093/eurjhf/hfs026 of long term mortality in men but not in women with heart failure. Eur Heart J. (2003) 24:2046–53 doi: 10.1016/j.ehj.2003.0 Conflict of Interest: The authors declare that the research was conducted in the 7.007 absence of any commercial or financial relationships that could be construed as a 2. Taylor CJ, Ordóñez-Mena JM, Jones NR, Roalfe AK, Lay-Flurrie S, Marshall potential conflict of interest. T, et al. National trends in heart failure mortality in men and women, United Kingdom, 2000–2017. Eur J Heart Fail. (2021) 23:3–12 doi: 10.1002/ejhf. Copyright © 2021 Martínez-Sellés, Ayesta, Díaz-Molina, Bayes-Genis and 1996 Baranchuk. This is an open-access article distributed under the terms of the Creative 3. Blumer V, Greene SJ, Wu A, Butler J, Ezekowitz JA, Lindenfeld Commons Attribution License (CC BY). The use, distribution or reproduction in J, et al. Sex differences in clinical course and patient-reported other forums is permitted, provided the original author(s) and the copyright owner(s) outcomes among patients hospitalized for heart failure. JACC Heart are credited and that the original publication in this journal is cited, in accordance Fail. (2021) 10:S2213-1779(21)00011-1 doi: 10.1016/j.jchf.2020.1 with accepted academic practice. No use, distribution or reproduction is permitted 2.011 which does not comply with these terms. Frontiers in Cardiovascular Medicine | www.frontiersin.org 2 May 2021 | Volume 8 | Article 690438