Department of Cardiology, Alfred Hospital, Melbourne, VIC, 3004, Australia.
Department of Cardiology, Herlev-Gentofte Hospital, Copenhagen, Denmark.
ESC Heart Fail. 2024 Oct;11(5):2557-2565. doi: 10.1002/ehf2.14794. Epub 2024 May 2.
Heart failure with preserved ejection fraction (HFpEF) is associated with an array of central and peripheral haemodynamic and metabolic changes. The exact pathogenesis of exercise limitation in HFpEF remains uncertain. Our aim was to compare lactate accumulation and central haemodynamic responses to exercise in patients with HFpEF, non-cardiac dyspnoea (NCD), and healthy volunteers.
Right heart catheterization with mixed venous blood gas and lactate measurements was performed at rest and during symptom-limited supine exercise. Multivariable analyses were conducted to determine the relationship between haemodynamic and biochemical parameters and their association with exercise capacity. Of 362 subjects, 198 (55%) had HFpEF, 103 (28%) had NCD, and 61 (17%) were healthy volunteers. This included 139 (70%) females with HFpEF, 77 (75%) in NCD (P = 0.41 HFpEF vs. NCD), and 31 (51%) in healthy volunteers (P < 0.001 HFpEF vs. volunteers). The median age was 71 (65, 75) years in HFpEF, 66 (57, 72) years in NCD, and 49 (38, 65) years in healthy volunteers (HFpEF vs. NCD or volunteer, both P < 0.001). Peak workload was lower in HFpEF compared with healthy volunteers [52 W (interquartile range 31-73), 150 W (125-175), P < 0.001], but not NCD [53 W (33, 75), P = 0.85]. Exercise lactate indexed to workload was higher in HFpEF at 0.08 mmol/L/W (0.05-0.11), 0.06 mmol/L/W (0.05-0.08; P = 0.016) in NCD, and 0.04 mmol/L/W (0.03-0.05; P < 0.001) in volunteers. Exercise cardiac index was 4.5 L/min/m (3.7-5.5) in HFpEF, 5.2 L/min/m (4.3-6.2; P < 0.001) in NCD, and 9.1 L/min/m (8.0-9.9; P < 0.001) in volunteers. Oxygen delivery in HFpEF was lower at 1553 mL/min (1175-1986) vs. 1758 mL/min (1361-2282; P = 0.024) in NCD and 3117 mL/min (2667-3502; P < 0.001) in the volunteer group during exercise. Predictors of higher exercise lactate levels in HFpEF following adjustment included female sex and chronic kidney disease (both P < 0.001).
HFpEF is associated with reduced exercise capacity secondary to both central and peripheral factors that alter oxygen utilization. This results in hyperlactataemia. In HFpEF, plasma lactate responses to exercise may be a marker of haemodynamic and cardiometabolic derangements and represent an important target for future potential therapies.
射血分数保留型心力衰竭（HFpEF）与一系列中枢和外周血液动力学和代谢变化有关。HFpEF 运动受限的确切发病机制仍不确定。我们的目的是比较 HFpEF 患者、非心源性呼吸困难（NCD）患者和健康志愿者在运动时乳酸的积累和中枢血液动力学反应。
在休息和症状限制仰卧运动时进行右心导管检查，同时进行混合静脉血气和乳酸测量。进行多变量分析以确定血液动力学和生化参数之间的关系及其与运动能力的关联。在 362 名受试者中，198 名（55%）患有 HFpEF，103 名（28%）患有 NCD，61 名（17%）为健康志愿者。这包括 139 名（70%）女性 HFpEF 患者，77 名（75%）NCD 患者（P=0.41 HFpEF 与 NCD 相比）和 31 名（51%）健康志愿者（P<0.001 HFpEF 与志愿者相比）。HFpEF 患者的中位年龄为 71（65，75）岁，NCD 患者为 66（57，72）岁，健康志愿者为 49（38，65）岁（HFpEF 与 NCD 或志愿者相比，均 P<0.001）。与健康志愿者相比，HFpEF 患者的峰值工作量较低[52 W（四分位距 31-73），150 W（125-175），P<0.001]，但与 NCD 患者相比[53 W（33-75），P=0.85]。HFpEF 患者运动时乳酸指数与工作量的比值为 0.08 mmol/L/W（0.05-0.11），NCD 患者为 0.06 mmol/L/W（0.05-0.08；P=0.016），志愿者为 0.04 mmol/L/W（0.03-0.05；P<0.001）。HFpEF 患者的运动心指数为 4.5 L/min/m（3.7-5.5），NCD 患者为 5.2 L/min/m（4.3-6.2；P<0.001），志愿者为 9.1 L/min/m（8.0-9.9；P<0.001）。HFpEF 患者在运动时的氧输送较低，为 1553 mL/min（1175-1986），而 NCD 患者为 1758 mL/min（1361-2282），志愿者组为 3117 mL/min（2667-3502；P<0.001）。HFpEF 患者运动时乳酸水平升高的预测因素包括女性和慢性肾脏病（均 P<0.001）。
HFpEF 与中心和外周因素共同导致运动能力下降，这些因素改变了氧气的利用。这导致高乳酸血症。在 HFpEF 中，运动时的血浆乳酸反应可能是血液动力学和心脏代谢紊乱的标志物，并代表未来潜在治疗的重要目标。
