A prolonged state of left ventricular pressure overload, commonly caused by hypertension and aortic valve disease, promotes remodelling of the myocardium that can progress to heart failure with preserved ejection fraction (HFpEF). In animal models, a major factor driving progression from pressure-overload hypertrophy (POH) to HFpEF is the activation and proliferation of an abnormal fibroblast phenotype that is resistant to apoptosis, degrades normal stromal matrix and is replaced with a fibrotic matrix structure. A similar fibroblast phenotype has been identified in the stroma of solid cancers. This cancer-associated fibroblast drives tumour growth and invasion. The proliferation and expansion of these abnormal fibroblast populations in both HFpEF and cancer contribute to progression of disease. In early-phase clinical trials, chemotherapeutic agents targeting cancer-associated fibroblasts had antitumour properties. In this Perspectives article, we postulate that, because the abnormal fibroblast populations in POH and cancer have identical characteristics, chemotherapeutic agents targeting the POH-related fibroblast might attenuate the development of myocardial fibrosis, a pathophysiological hallmark of HFpEF. These agents must be designed to target the abnormal fibroblasts with high specificity because many classes of chemotherapeutic drugs can themselves cause myocardial dysfunction and heart failure.

左心室压力超负荷的延长状态通常由高血压和主动脉瓣疾病引起，可促进心肌重构，并在射血分数（HFpEF）保持不变的情况下发展为心力衰竭。在动物模型中，驱动从压力超负荷肥大（POH）演变为HFpEF的主要因素是异常的成纤维细胞表型的激活和增殖，该表型对细胞凋亡具有抵抗力，可降解正常基质基质并被纤维化基质结构取代。在实体癌的基质中已鉴定出相似的成纤维细胞表型。这种与癌症相关的成纤维细胞驱动肿瘤的生长和侵袭。这些异常的成纤维细胞群体在HFpEF和癌症中的增殖和扩展均导致疾病进展。在早期临床试验中，靶向与癌症相关的成纤维细胞的化学治疗剂具有抗肿瘤特性。在此《观点》文章中，我们假设，由于POH和癌症中异常的成纤维细胞数量具有相同的特征，针对POH相关成纤维细胞的化学治疗剂可能会减弱心肌纤维化的发展，这是HFpEF的病理生理学特征。必须设计这些药剂以高特异性地靶向异常的成纤维细胞，因为许多类型的化学治疗药物本身都可能引起心肌功能障碍和心力衰竭。靶向POH相关成纤维细胞的化学治疗剂可能会减弱心肌纤维化的发展，这是HFpEF的病理生理学标志。必须设计这些药剂以高特异性地靶向异常的成纤维细胞，因为许多类型的化学治疗药物本身都可能引起心肌功能障碍和心力衰竭。靶向POH相关成纤维细胞的化学治疗剂可能会减弱心肌纤维化的发展，这是HFpEF的病理生理学特征。必须设计这些药剂以高特异性地靶向异常的成纤维细胞，因为许多种类的化学治疗药物本身都可能引起心肌功能障碍和心力衰竭。