Learning from our differences: insights from a global heart failure registry
Authors: Sandhir B Prasad, John J Atherton
Journal: The Lancet Global Health (2024)

The global prevalence of heart failure has doubled over the last 20 years, with the fastest growth occurring in low-income and middle-income countries, which comprise the majority of cases.1Wei S Miranda JJ Mamas MA et al.Sex differences in the etiology and burden of heart failure across country income level: analysis of 204 countries and territories 1990–2019.Eur Heart J Qual Care Clin Outcomes. 2023; 9: 662-672Crossref Scopus (3) Google Scholar However, these countries have been under-represented in most heart failure registries, with few studies comparing the quality of care in men and women across different geographical regions. In The Lancet Global Health, Marjan Walli-Attaei and colleagues2Walli-Attaei M Joseph P Johansson I et al.Characteristics, management, and outcomes in women and men with congestive heart failure in 40 countries at different economic levels: an analysis from the Global Congestive Heart Failure (G-CHF) registry.Lancet Glob Health. 2024; (published online Jan 10.)https://doi.org/10.1016/S2214-109X(23)00557-0Google Scholar compare baseline characteristics and process and outcome health-care measures in 23 341 patients with heart failure from five of the six inhabited continents enrolled in the Global Congestive Heart Failure registry and followed up for an average of 2·6 years. The authors are to be congratulated on undertaking such a large, prospective study with a structured approach to data collection which has included lower-middle-income and low-income countries, where systematic data are often difficult to acquire given the lack of large administrative databases. Consistent with previous registries, patients with heart failure from lower-middle-income and low-income countries were younger than those from high-income or upper middle-income countries.3Atherton JJ Hayward CS Wan Ahmad WA et al.Patient characteristics from a regional multicenter database of acute decompensated heart failure in Asia Pacific (ADHERE International-Asia Pacific).J Card Fail. 2012; 18: 82-88Summary Full Text Full Text PDF PubMed Scopus (136) Google Scholar Furthermore, whereas women enrolled in high-income or upper middle-income countries were older than men, women enrolled in lower-middle-income and low-income countries were younger.2Walli-Attaei M Joseph P Johansson I et al.Characteristics, management, and outcomes in women and men with congestive heart failure in 40 countries at different economic levels: an analysis from the Global Congestive Heart Failure (G-CHF) registry.Lancet Glob Health. 2024; (published online Jan 10.)https://doi.org/10.1016/S2214-109X(23)00557-0Google Scholar Women had lower levels of education regardless of country economic status, although the differences were more pronounced in lower-middle-income and low-income countries. Similar to previous studies,4Lam CSP Arnott C Beale AL et al.Sex differences in heart failure.Eur Heart J. 2019; 40 (368c): 3859Crossref PubMed Scopus (319) Google Scholar, 5Stolfo D Uijl A Vedin O et al.Sex-based differences in heart failure across the ejection fraction spectrum: phenotyping, and prognostic and therapeutic implications.JACC Heart Fail. 2019; 7: 505-515Crossref PubMed Scopus (101) Google Scholar, 6Tromp J Ezekowitz JA Ouwerkerk W et al.Global variations according to sex in patients hospitalized for heart failure in the REPORT-HF registry.JACC Heart Fail. 2023; 11: 1262-1271Crossref Scopus (2) Google Scholar, 7Motiejūnaitė J Akiyama E Cohen-Solal A et al.The association of long-term outcome and biological sex in patients with acute heart failure from different geographic regions.Eur Heart J. 2020; 41: 1357-1364Crossref PubMed Scopus (41) Google Scholar, 8Keshvani N Shah S Ayodele I et al.Sex differences in long-term outcomes following acute heart failure hospitalization: findings from the Get With The Guidelines-Heart Failure registry.Eur J Heart Fail. 2023; 25: 1544-1554Crossref Scopus (3) Google Scholar a higher proportion of men compared with women had heart failure with reduced ejection fraction, probably related to higher rates of underlying ischaemic heart disease, diabetes, and tobacco and alcohol consumption. Meanwhile, higher proportions of women had heart failure with preserved ejection fraction, hypertensive heart failure, and valvular rheumatic heart disease.2Walli-Attaei M Joseph P Johansson I et al.Characteristics, management, and outcomes in women and men with congestive heart failure in 40 countries at different economic levels: an analysis from the Global Congestive Heart Failure (G-CHF) registry.Lancet Glob Health. 2024; (published online Jan 10.)https://doi.org/10.1016/S2214-109X(23)00557-0Google Scholar Although the use of investigations and medications were broadly similar, there were some notable differences in patients with a reduced ejection fraction, including higher mineralocorticoid receptor antagonist, digoxin, and diuretic prescription rates in women compared with men, especially in lower-middle-income and low-income countries.2Walli-Attaei M Joseph P Johansson I et al.Characteristics, management, and outcomes in women and men with congestive heart failure in 40 countries at different economic levels: an analysis from the Global Congestive Heart Failure (G-CHF) registry.Lancet Glob Health. 2024; (published online Jan 10.)https://doi.org/10.1016/S2214-109X(23)00557-0Google Scholar While this finding could be related to women experiencing worse symptoms and signs, β-blocker and sacubitril–valsartan prescription rates were lower in women, the latter only observed in lower-middle-income and low-income countries, possibly reflecting economic drivers.2Walli-Attaei M Joseph P Johansson I et al.Characteristics, management, and outcomes in women and men with congestive heart failure in 40 countries at different economic levels: an analysis from the Global Congestive Heart Failure (G-CHF) registry.Lancet Glob Health. 2024; (published online Jan 10.)https://doi.org/10.1016/S2214-109X(23)00557-0Google Scholar These economic drivers could also explain why fewer women received implantable cardioverter defibrillators compared with men, which has been a consistent finding in other studies,4Lam CSP Arnott C Beale AL et al.Sex differences in heart failure.Eur Heart J. 2019; 40 (368c): 3859Crossref PubMed Scopus (319) Google Scholar, 5Stolfo D Uijl A Vedin O et al.Sex-based differences in heart failure across the ejection fraction spectrum: phenotyping, and prognostic and therapeutic implications.JACC Heart Fail. 2019; 7: 505-515Crossref PubMed Scopus (101) Google Scholar, 6Tromp J Ezekowitz JA Ouwerkerk W et al.Global variations according to sex in patients hospitalized for heart failure in the REPORT-HF registry.JACC Heart Fail. 2023; 11: 1262-1271Crossref Scopus (2) Google Scholar although lower rates of ischaemic heart disease coupled with concerns regarding device-related complications in women might influence shared decision making. An intriguing observation was that, despite women experiencing worse symptoms, signs, and quality of life compared with men, they had similar hospitalisation rates and a lower adjusted mortality, regardless of country economic status, geographical region, and ejection fraction.2Walli-Attaei M Joseph P Johansson I et al.Characteristics, management, and outcomes in women and men with congestive heart failure in 40 countries at different economic levels: an analysis from the Global Congestive Heart Failure (G-CHF) registry.Lancet Glob Health. 2024; (published online Jan 10.)https://doi.org/10.1016/S2214-109X(23)00557-0Google Scholar The authors considered whether delayed diagnosis could contribute to worse symptoms and signs; however, this explanation would not be consistent with the better adjusted survival seen in women. Indeed, women with heart failure have consistently reported worse quality of life,4Lam CSP Arnott C Beale AL et al.Sex differences in heart failure.Eur Heart J. 2019; 40 (368c): 3859Crossref PubMed Scopus (319) Google Scholar, 5Stolfo D Uijl A Vedin O et al.Sex-based differences in heart failure across the ejection fraction spectrum: phenotyping, and prognostic and therapeutic implications.JACC Heart Fail. 2019; 7: 505-515Crossref PubMed Scopus (101) Google Scholar, 6Tromp J Ezekowitz JA Ouwerkerk W et al.Global variations according to sex in patients hospitalized for heart failure in the REPORT-HF registry.JACC Heart Fail. 2023; 11: 1262-1271Crossref Scopus (2) Google Scholar, 9Lainščak M Milinković I Polovina M et al.Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry.Eur J Heart Fail. 2020; 22: 92-102Crossref PubMed Scopus (63) Google Scholar but have a lower mortality compared with men in most studies.4Lam CSP Arnott C Beale AL et al.Sex differences in heart failure.Eur Heart J. 2019; 40 (368c): 3859Crossref PubMed Scopus (319) Google Scholar, 5Stolfo D Uijl A Vedin O et al.Sex-based differences in heart failure across the ejection fraction spectrum: phenotyping, and prognostic and therapeutic implications.JACC Heart Fail. 2019; 7: 505-515Crossref PubMed Scopus (101) Google Scholar, 7Motiejūnaitė J Akiyama E Cohen-Solal A et al.The association of long-term outcome and biological sex in patients with acute heart failure from different geographic regions.Eur Heart J. 2020; 41: 1357-1364Crossref PubMed Scopus (41) Google Scholar, 9Lainščak M Milinković I Polovina M et al.Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry.Eur J Heart Fail. 2020; 22: 92-102Crossref PubMed Scopus (63) Google Scholar However, a recent analysis from the Registry to Assess Medical Practice With Longitudinal Observation for the Treatment of Heart Failure, involving patients hospitalised with heart failure across 44 countries, reported that the female survival advantage was only seen in countries with less inequality of income.6Tromp J Ezekowitz JA Ouwerkerk W et al.Global variations according to sex in patients hospitalized for heart failure in the REPORT-HF registry.JACC Heart Fail. 2023; 11: 1262-1271Crossref Scopus (2) Google Scholar An additional consideration that has not been well explored in heart failure is the relative contribution of biological sex and gender identity to quality of life and health outcomes.10Pelletier R Khan NA Cox J et al.Sex versus gender-related characteristics: which predicts outcome after acute coronary syndrome in the young?.J Am Coll Cardiol. 2016; 67: 127-135Crossref PubMed Scopus (197) Google Scholar Based on having broadly similar use of diagnostic investigations and prescription rates, coupled with lower adjusted mortality, the authors reasonably concluded that it would be inappropriate to consider that male patients were advantaged compared with female patients.2Walli-Attaei M Joseph P Johansson I et al.Characteristics, management, and outcomes in women and men with congestive heart failure in 40 countries at different economic levels: an analysis from the Global Congestive Heart Failure (G-CHF) registry.Lancet Glob Health. 2024; (published online Jan 10.)https://doi.org/10.1016/S2214-109X(23)00557-0Google Scholar However, although adjusting for age, biological covariates, and disease severity might be appropriate, adjusting for behavioural and treatment-based measures of inequity could disguise the impact of sex on clinical outcomes. To address this, the authors undertook sensitivity analyses and showed that the female survival advantage persisted when education, treatment history, and medication use were removed as covariates from the multivariable models. A recent analysis from the Get With The Guidelines Heart Failure registry also confirmed that women with heart failure had lower adjusted mortality than men, although when they compared men and women with heart failure with the age-and-sex-matched US population, women experienced greater years of life lost. It would be of interest to undertake similar analyses in lower-middle-income and low-income countries.8Keshvani N Shah S Ayodele I et al.Sex differences in long-term outcomes following acute heart failure hospitalization: findings from the Get With The Guidelines-Heart Failure registry.Eur J Heart Fail. 2023; 25: 1544-1554Crossref Scopus (3) Google Scholar What remains clear is that, regardless of country income status, geographical region, sex, or ejection fraction, patients with heart failure continue to experience poor outcomes. Future studies are required to explore why women experience worse quality of life and men have a higher mortality rate despite contemporary therapy, recognising that both measures are important treatment goals for our patients. We declare no competing interests. Characteristics, management, and outcomes in women and men with congestive heart failure in 40 countries at different economic levels: an analysis from the Global Congestive Heart Failure (G-CHF) registryThe underlying cause of heart failure and ejection fraction phenotype differ between women and men, as do the severity of symptoms. Heart failure treatments (except ICD use) were not consistently in favour of one sex. Paradoxically, while the rates of hospitalisations were similar among women and men, the risk of death was lower among women. These patterns were consistent regardless of the economic status of the countries. The higher mortality among men is unexplained and warrants further study. Full-Text PDF Open Access