Heart failure in transgender people: evidence synthesis and methodological limitations

Heart failure (HF) represents a major cardiovascular condition with a well-characterised epidemiology in the general population. However, despite cardiovascular risk factors having been examined in transgender individuals receiving gender-affirming hormone therapy (GAHT), HF-specific evidence in this population remains fragmented across heterogeneous epidemiological datasets. Therefore, we aimed to synthesise available evidence on HF in transgender populations and to evaluate methodological factors influencing heart failure risk assessment. We conducted a systematic review of studies reporting heart failure outcomes in transgender populations. Where studies provided extractable estimates and documented or inferred GAHT exposure with a cisgender comparator group, exploratory random-effects quantitative syntheses were conducted. Both administrative and clinical datasets were included. Transgender population identification, GAHT exposure ascertainment, HF outcome definition, comparator selection, and study-level risk of bias were assessed. Only a limited number of eligible studies were identified. Seven full-text studies met the inclusion criteria. Transgender identification methods, GAHT ascertainment, HF definitions, comparator groups, and baseline population characteristics varied substantially across studies. Effect estimates varied markedly across administrative and clinical datasets. None of the included studies systematically distinguished between HF phenotypes. In exploratory quantitative syntheses, including additional suitable conference abstracts, pooled estimates were non-significant yet highly heterogeneous for both transgender versus cisgender individuals (odds ratio [OR] 1.10, 95% CI 0.60–2.01; I²=98.9%) and transgender men versus cisgender women (OR 1.04, 95% CI 0.38–2.86; I²=99.5%). Current evidence is insufficient to determine whether transgender status or GAHT exposure is associated with the risk of heart failure. Substantial heterogeneity appears largely driven by differences in transgender identification methods, exposure assessment, and the absence of HF phenotype classification. These structural limitations constrain heart failure risk evaluation in transgender populations and highlight the need for improved epidemiological data infrastructure and phenotype-specific cardiovascular registries.