Heart Failure with preserved Ejection Fraction (HFpEF) is an increasingly prevalent clinical condition associated with cardiovascular aging, characterized by different pathophysiological mechanisms and poor outcomes. In this manuscript, we analysed the main differences in terms of updated diagnostic criteria and patients' selection in the most recent HFpEF trials. Recent algorithm purposed for HFpEF diagnosis, does not reflect common criteria adopted in clinical trials. Patients included in the larger studies experienced different characteristics in terms of clinical presentation and echocardiographic features. Current concerns complicate results interpretation and could hypothesize different stages of disease progression, rather than different cardiac phenotypes. Both the lack of diagnostic standardization and the population heterogeneity, might explain why trials investigating the effects of different therapeutic interventions failed to show improved outcomes for patients with HFpEF. Accordingly, we propose to exceed current view mainly based on the morphological adaptations evaluating patients' characterisation, their cardiovascular risk, associated diseases, and structural features consistent with disease progression. Detailed clinical, imaging and biological characterisation of this population, along with the identification of mechanisms linked with disease progression and prognosis, would allow for tailored treatments and provide important mechanistic insights into the complex HFpEF pathophysiology.

射血分数保留的心力衰竭 (HFpEF) 是一种日益普遍的与心血管衰老相关的临床疾病，其特点是不同的病理生理机制和不良结果。在这份手稿中，我们分析了最近 HFpEF 试验中更新的诊断标准和患者选择方面的主要差异。最近用于 HFpEF 诊断的算法并未反映临床试验中采用的通用标准。纳入大型研究的患者在临床表现和超声心动图特征方面经历了不同的特征。目前的担忧使结果解释复杂化，并且可以假设疾病进展的不同阶段，而不是不同的心脏表型。缺乏诊断标准化和人群异质性，可能解释了为什么调查不同治疗干预效果的试验未能显示 HFpEF 患者的预后有所改善。因此，我们建议超越目前的观点，主要基于评估患者特征、心血管风险、相关疾病和与疾病进展一致的结构特征的形态学适应。该人群的详细临床、影像学和生物学特征，以及与疾病进展和预后相关的机制的鉴定，将允许定制治疗并为复杂的 HFpEF 病理生理学提供重要的机制见解。我们建议超越目前的观点，主要基于评估患者特征、心血管风险、相关疾病和与疾病进展一致的结构特征的形态学适应。该人群的详细临床、影像学和生物学特征，以及与疾病进展和预后相关的机制的鉴定，将允许定制治疗并为复杂的 HFpEF 病理生理学提供重要的机制见解。我们建议超越目前的观点，主要基于评估患者特征、心血管风险、相关疾病和与疾病进展一致的结构特征的形态学适应。该人群的详细临床、影像学和生物学特征，以及与疾病进展和预后相关的机制的鉴定，将允许定制治疗并为复杂的 HFpEF 病理生理学提供重要的机制见解。