Heart failure (HF) is the final common end point of multiple metabolic and cardiovascular diseases and imposes a significant health care burden worldwide. Despite significant improvements in clinical management and outcomes, morbidity and mortality remain high and there remains an indisputable need for improved treatment options. The pathophysiology of HF is complex and covers a spectrum of clinical presentations from HF with reduced ejection fraction (HFrEF) (≤40% EF) through to HF with preserved EF (HFpEF), with HFpEF patients demonstrating a reduced ability of the heart to relax despite an EF maintained above 50%. Prior to the last decade, the majority of clinical trials and animal models addressed HFrEF. Despite growing efforts recently to understand underlying mechanisms of HFpEF and find effective therapies for its treatment, clinical trials in patients with HFpEF have failed to demonstrate improvements in mortality. A significant obstacle to therapeutic innovation in HFpEF is the absence of preclinical models including large animal models which, unlike rodents, permit detailed instrumentation and extensive imaging and sampling protocols. Although several large animal models of HFpEF have been reported, none fulfil all the features present in human disease and few demonstrate progression to frank decompensated HF. This review summarizes well-established models of HFrEF in pigs, dogs and sheep and discusses attempts to date to model HFpEF in these species.

中文翻译：

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心力衰竭的大型动物模型：射血分数减少与保留

心力衰竭（HF）是多种代谢和心血管疾病的最终共同终点，给全世界带来了巨大的医疗保健负担。尽管临床管理和结果有了显着改善，但发病率和死亡率仍然很高，毫无疑问仍然需要改进的治疗方案。心力衰竭的病理生理学很复杂，涵盖从射血分数降低的心力衰竭 (HFrEF) (≤40% EF) 到射血分数保留的心力衰竭 (HFpEF) 的一系列临床表现，HFpEF 患者表现出心脏舒张能力降低尽管 EF 保持在 50% 以上。在过去十年之前，大多数临床试验和动物模型都针对 HFrEF。尽管最近越来越多的努力来了解 HFpEF 的潜在机制并找到有效的治疗方法，但 HFpEF 患者的临床试验未能证明死亡率有所改善。HFpEF 治疗创新的一个重大障碍是缺乏临床前模型，包括大型动物模型，与啮齿动物不同，大型动物模型允许使用详细的仪器和广泛的成像和采样方案。尽管已经报道了几种大型 HFpEF 动物模型，但没有一种模型能够满足人类疾病中存在的所有特征，并且很少有模型显示进展为明显的失代偿性 HF。本综述总结了猪、狗和羊中成熟的 HFrEF 模型，并讨论了在这些物种中建立 HFpEF 模型的尝试。