Heart failure with preserved ejection fraction (HFpEF) is a major public health concern. Its outcome is poor and, as of today, barely any treatments have been able to decrease its morbidity or mortality. Cardiosphere-derived cells (CDCs) are heart cell products with anti-fibrotic, anti-inflammatory and angiogenic properties. Here, we tested the efficacy of CDCs in improving left ventricular (LV) structure and function in pigs with HFpEF. Fourteen chronically instrumented pigs received continuous angiotensin II infusion for 5 weeks. LV function was investigated through hemodynamic measurements and echocardiography at baseline, after 3 weeks of angiotensin II infusion before three-vessel intra-coronary CDC (n = 6) or placebo (n = 8) administration and 2 weeks after treatment (i.e., at completion of the protocol). As expected, arterial pressure was significantly and similarly increased in both groups. This was accompanied by LV hypertrophy that was not affected by CDCs. LV systolic function remained similarly preserved during the whole protocol in both groups. In contrast, LV diastolic function was impaired (increases in Tau, LV end-diastolic pressure as well as E/A, E/E’septal and E/E’lateral ratios) but CDC treatment significantly improved all of these parameters. The beneficial effect of CDCs on LV diastolic function was not explained by reduced LV hypertrophy or increased arteriolar density; however, interstitial fibrosis was markedly reduced. Three-vessel intra-coronary administration of CDCs improves LV diastolic function and reduces LV fibrosis in this hypertensive model of HFpEF.

射血分数保留的心力衰竭（HFpEF）是一个主要的公共卫生问题。其结果很差，截至目前，几乎没有任何治疗方法能够降低其发病率或死亡率。心脏球衍生细胞（CDC）是具有抗纤维化、抗炎和血管生成特性的心脏细胞产物。在这里，我们测试了 CDC 在改善 HFpEF 猪的左心室 (LV) 结构和功能方面的功效。14 头长期使用仪器的猪接受连续血管紧张素 II 输注 5 周。通过血流动力学测量和超声心动图检查基线、血管紧张素 II 输注 3 周后、三血管冠状动脉内 CDC ( n  = 6) 或安慰剂 ( n  = 8) 给药前以及治疗后 2 周（即完成时），通过血流动力学测量和超声心动图检查左心室功能协议）。正如预期的那样，两组的动脉压均显着且相似地增加。这伴随着左心室肥厚，但不受 CDC 的影响。在整个方案期间，两组的左心室收缩功能保持相似的状态。相反，左心室舒张功能受损（Tau、左心室舒张末压以及 E/A、E/E' 间隔和 E/E' 侧向比增加），但 CDC 治疗显着改善了所有这些参数。CDC 对左室舒张功能的有益作用不能通过减少左室肥厚或增加小动脉密度来解释；然而，间质纤维化明显减少。在 HFpEF 高血压模型中，三血管冠状动脉内注射 CDC 可改善左心室舒张功能并减少左心室纤维化。