Department of Medicine, Cardiovascular Division, University of Wisconsin-Madison, Wisconsin, USA.
Biomedical Engineering, University of Wisconsin-Madison, Wisconsin, USA.
Function (Oxf). 2022 Apr 30;3(4):zqac022. doi: 10.1093/function/zqac022. eCollection 2022.
Deep phenotyping of pulmonary hypertension (PH) with multimodal diagnostic exercise interventions can lead to early focused therapeutic interventions. Herein, we report methods to simultaneously assess pulmonary impedance, differential biventricular myocardial strain, and right ventricular:pulmonary arterial (RV:PA) uncoupling during exercise, which we pilot in subjects with suspected PH. As proof-of-concept, we show that four subjects with different diagnoses [pulmonary arterial hypertension (PAH); chronic thromboembolic disease (CTEPH); PH due to heart failure with preserved ejection fraction (PH-HFpEF); and noncardiac dyspnea (NCD)] have distinct patterns of response to exercise. RV:PA coupling assessment with exercise was highest-to-lowest in this order: PAH > CTEPH > PH-HFpEF > NCD. Input impedance (Z) with exercise was highest in precapillary PH (PAH, CTEPH), followed by PH-HFpEF and NCD. Characteristic impedance (Z) tended to decline with exercise, except for the PH-HFpEF subject (initial Zc increase at moderate workload with subsequent decrease at higher workload with augmentation in cardiac output). Differential myocardial strain was normal in PAH, CTEPH, and NCD subjects and lower in the PH-HFpEF subject in the interventricular septum. The combination of these metrics allowed novel insights into mechanisms of RV:PA uncoupling. For example, while the PH-HFpEF subject had hemodynamics comparable to the NCD subject at rest, with exercise coupling dropped precipitously, which can be attributed (by decreased myocardial strain of interventricular septum) to poor support from the left ventricle (LV). We conclude that this deep phenotyping approach may distinguish afterload sensitive vs. LV-dependent mechanisms of RV:PA uncoupling in PH, which may lead to novel therapeutically relevant insights.
对肺动脉高压（PH）进行多模态诊断性运动干预的深度表型分析可导致早期针对性的治疗干预。在此，我们报告了一种方法，可在怀疑患有 PH 的患者中同时评估运动期间的肺阻抗、左右心室心肌应变的差异以及右心室：肺动脉（RV：PA）解耦。作为概念验证，我们显示了 4 名不同诊断的患者[肺动脉高压（PAH）；慢性血栓栓塞性疾病（CTEPH）；射血分数保留的心力衰竭所致 PH（PH-HFpEF）；非心源性呼吸困难（NCD）]对运动的反应有不同的模式。RV：PA 耦合评估的运动顺序为 PAH > CTEPH > PH-HFpEF > NCD。运动时的输入阻抗（Z）以该顺序递增：PAH、CTEPH、PH-HFpEF 和 NCD。除 PH-HFpEF 患者（中度工作负荷时初始 Zc 增加，随后高工作负荷时降低，心输出量增加）外，特征阻抗（Zc）趋于随运动降低。PAH、CTEPH 和 NCD 患者的左右心室心肌应变正常，而 PH-HFpEF 患者的应变较低。这些指标的结合使我们对 RV：PA 解耦的机制有了新的认识。例如，PH-HFpEF 患者在休息时的血流动力学与 NCD 患者相当，但在运动时耦合急剧下降，这可能归因于（由于室间隔的心肌应变降低）左心室（LV）支持不足。我们得出结论，这种深度表型分析方法可以区分 PH 中 RV：PA 解耦的后负荷敏感与 LV 依赖性机制，这可能为新的治疗相关见解提供依据。
