Heart Failure in Women: Epidemiological and Prognostic Insights

Data are collected in a centralized, encrypted electronic case report form. Baseline variables include demographics, cardiovascular risk factors and comorbidity, previous cardiological history and prior medication; sex-specific risk factors recorded in the clinical history of the index admission (number of pregnancies and deliveries; preeclampsia, eclampsia or HELLP syndrome; gestational hypertension and gestational diabetes; preterm delivery; intrauterine growth restriction or small-for-gestational-age newborn; peripartum cardiomyopathy; recurrent pregnancy loss; menopausal status and age at menopause; hormone replacement therapy; polycystic ovary syndrome; and endometriosis); previous cardiotoxic cancer therapy (chemotherapy or radiotherapy), recorded with the oncological history as a female-predominant risk factor; individual social determinants (net monthly household income, number of people in the household and educational attainment); clinical features of the index episode; laboratory, electrocardiographic and echocardiographic data; cardiac magnetic resonance, coronary angiography and other investigations when performed; treatment at discharge by drug class and dose band, with adverse effects and whether these led to dose reduction or withdrawal; devices and cardiac interventions; and the Barthel index, the Pfeiffer questionnaire, the five-item Geriatric Depression Scale and the 12-item Kansas City Cardiomyopathy Questionnaire.

At each follow-up visit (3, 6 and 12 months) the following are recorded: functional class, physical examination for residual congestion, weight and blood pressure, laboratory tests and electrocardiogram, current treatment with doses, tolerability and adverse effects, emergency department attendances and day-hospital treatments for heart failure, hospitalizations for heart failure, for other cardiovascular causes and for non-cardiovascular causes, referral to cardiac rehabilitation and referral for advanced therapies. Echocardiography is performed at the index admission, once during follow-up at the 3- or 6-month visit, and again by the 12-month visit. Vital status and cause of death are recorded throughout; clinical events are ascertained by the site investigator from the clinical and regional electronic health records, without central adjudication. Functional and health-status scales are repeated at 12 months.

To document and control selection bias, each site declares a fixed screening frame in advance and maintains a screening log recording the number of women screened, the number confirmed eligible, the number enrolled, and the number of eligible women not enrolled with the reason. Participation rates will be reported by site.

The sample size was calculated for descriptive precision: with the most conservative proportion (p = 0.50), 95% confidence and an absolute precision of 5%, 385 evaluable women are required; allowing for 10% loss to follow-up over 12 months, 430 women will be recruited. Results will be presented overall and by ejection fraction phenotype according to the 2026 European Society of Cardiology definitions (reduced, below 50%; preserved, 50% or higher; also reporting 40% or lower and 41-49% separately) and by age (under 75 or 75 years and older). Time to the composite endpoint will be analyzed with Kaplan-Meier curves and Cox models with standard errors clustered by center; all secondary analyses are exploratory. The comparison with the men of the TIDY-HF registry will include all women for clinical profile and investigations, and women with an ejection fraction of 40% or lower, the population enrolled in TIDY-HF, for the class and dose of foundational medical therapy, with adjustment for age.