Ridderbos Floris-Jan S, Hoendermis Elke S, van Hassel Gaston, Ebels Tjark, van Melle Joost P, Berger Rolf M F
Department of Pediatric Cardiology, Center for Congenital Heart Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Cardiology, Center for Congenital Heart Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Am J Physiol Heart Circ Physiol. 2025 Aug 1;329(2):H366-H373. doi: 10.1152/ajpheart.00105.2025. Epub 2025 Jun 12.
The hemodynamics of Fontan pathophysiology and the effects of pulmonary vasodilator therapy are insufficiently understood. The aim was to evaluate hemodynamic responses to dobutamine-induced stress and the effect of concomitant acute pulmonary vasodilation (APV) testing in patients with a Fontan circulation to identify hemodynamic phenotypes. Sixteen adult patients undergoing cardiac catheterization for clinical indication were included. Hemodynamic phenotyping was performed during baseline, dobutamine-induced stress, and concomitant APV [inhaled nitric oxide with fraction of inspired oxygen ([Formula: see text]) 1.0]. Pulmonary vascular disease (PVD) was defined by pulmonary vascular resistance (PVR) > 2 Wood units or pulmonary artery pressure/pulmonary blood flow slope (mPAP/Qp) > 3 mmHg/L/min. Patients were assigned to without PVD ( = 8) or with PVD ( = 8 mPAP/Qp > 3 with = 3 PVR > 2). For the total group, median cardiac output (Qs) was 5.2 L/min and increased to 7.3 L/min with dobutamine ( = 0.005) without further change with APV ( = 0.255). However, subgroup analysis revealed that during dobutamine, the increase in Qs occurred only in (+3.5 L/min, = 0.012), and Qs decreased in APV (-1.3 L/min, = 0.0036). In contrast, in , Qs did not change with dobutamine ( = 0.236) nor with APV ( = 0.327). However, in contrast to ( = 0.889), in , Qp increased with APV (+1.3 L/min, = 0.017), whereas the mPAP/Qp slope improved significantly (6.2 to 1 mmHg/L/min, = 0.017). Suggesting that APV improved Qp and oxygenation in patients with PVD but had negative effects in those without PVD. This study shows that hemodynamic response to dobutamine-induced stress and APV differs in patients with a Fontan circulation depending on the presence of pulmonary vascular disease. Hemodynamic phenotyping with sophisticated identification of pulmonary vascular disease potentially allows for patient-tailored treatment. Hemodynamic response to dobutamine-induced stress and acute pulmonary vasodilation testing differs in patients with a Fontan circulation depending on the presence of pulmonary vascular disease. This study supports that there is no hemodynamic rationale for pulmonary vasodilator therapy for the general Fontan population. The use of mPAP/Qp slopes and acute pulmonary vasodilator testing should be considered to identify pulmonary vascular disease. Hemodynamic phenotyping with the identification of pulmonary vascular disease potentially allows for patient-tailored treatment.
对Fontan病理生理学的血流动力学以及肺血管扩张剂治疗的效果了解不足。目的是评估接受Fontan循环的患者对多巴酚丁胺诱导应激的血流动力学反应以及伴随急性肺血管扩张（APV）测试的效果，以确定血流动力学表型。纳入了16名因临床指征接受心导管检查的成年患者。在基线、多巴酚丁胺诱导应激以及伴随APV [吸入一氧化氮，吸入氧分数（[公式：见正文]）为1.0]期间进行血流动力学表型分析。肺血管疾病（PVD）定义为肺血管阻力（PVR）>2伍德单位或肺动脉压力/肺血流量斜率（mPAP/Qp）>3 mmHg/L/min。患者被分为无PVD组（=8）或有PVD组（=8，mPAP/Qp>3，其中=3，PVR>2）。对于总体组，中位心输出量（Qs）为5.2 L/min，多巴酚丁胺作用下增加至7.3 L/min（=0.005），APV后无进一步变化（=0.255）。然而，亚组分析显示，在多巴酚丁胺作用期间，Qs仅在组中增加（+3.5 L/min，=0.012），而在APV期间Qs下降（-1.3 L/min，=0.0036）。相比之下，在组中，多巴酚丁胺和APV作用下Qs均无变化（分别为=0.236和=0.327）。然而，与组（=0.889）不同，在组中，APV作用下Qp增加（+1.3 L/min，=0.017），而mPAP/Qp斜率显著改善（从6.2降至1 mmHg/L/min，=0.017）。这表明APV改善了PVD患者的Qp和氧合，但对无PVD患者有负面影响。本研究表明，接受Fontan循环的患者对多巴酚丁胺诱导应激和APV的血流动力学反应因是否存在肺血管疾病而异。通过精确识别肺血管疾病进行血流动力学表型分析可能有助于实现个体化治疗。接受Fontan循环的患者对多巴酚丁胺诱导应激和急性肺血管扩张测试的血流动力学反应因是否存在肺血管疾病而异。本研究支持，对于一般Fontan人群，肺血管扩张剂治疗没有血流动力学依据。应考虑使用mPAP/Qp斜率和急性肺血管扩张测试来识别肺血管疾病。通过识别肺血管疾病进行血流动力学表型分析可能有助于实现个体化治疗。
