Department of Bioengineering, Imperial College London, London, UK.
BHF Centre of Research Excellence, Imperial College London, London, UK.
J Physiol. 2024 Feb;602(4):663-681. doi: 10.1113/JP285475. Epub 2024 Feb 7.
Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) causes biomechanical and functional aberrations, leading to a high risk of progression to hypoplastic left heart syndrome (HLHS) at birth. Fetal aortic valvuloplasty (FAV) can resolve outflow obstruction and may reduce progression risk. However, it is currently difficult to accurately predict which patients will respond to the intervention and become functionally biventricular (BV) at birth, as opposed to becoming functionally univentricular (UV). This prediction is important for patient selection, parental counselling, and surgical planning. Therefore, we investigated whether biomechanics parameters from pre-FAV image-based computations could robustly distinguish between CAS-eHLHS cases with BV or UV outcomes in a retrospective cohort. To do so we performed image-based finite element biomechanics modelling of nine CAS-eHLHS cases undergoing intervention and six healthy fetal control hearts, and found that a biomechanical parameter, peak systolic myofibre stress, showed a uniquely large difference between BV and UV cases, which had a larger magnitude effect than echocardiography parameters. A simplified equation was derived for quick and easy estimation of myofibre stress from echo measurements via principal component analysis. When tested on a retrospective cohort of 37 CAS-eHLHS cases, the parameter outperformed other parameters in predicting UV versus BV outcomes, and thus has a high potential of improving outcome predictions, if incorporated into patient selection procedures. Physiologically, high myocardial stresses likely indicate a healthier myocardium that can withstand high stresses and resist pathological remodelling, which can explain why it is a good predictor of BV outcomes. KEY POINTS: Predicting the morphological birth outcomes (univentricular versus biventricular) of fetal aortic valvuloplasty for fetal aortic stenosis with evolving HLHS is important for accurate patient selection, parental counselling and management decisions. Computational simulations show that a biomechanics parameter, pre-intervention peak systolic myofibre stress, is uniquely robust in distinguishing between such outcomes, outperforming all echo parameters. An empirical equation was developed to quickly compute peak systolic myofibre stress from routine echo measurements and was the best predictor of outcomes among a wide range of parameters tested.
胎儿严重主动脉瓣狭窄伴进行性左心发育不良综合征（CAS-eHLHS）引起生物力学和功能异常，导致出生时进展为左心发育不良综合征（HLHS）的风险较高。胎儿主动脉瓣成形术（FAV）可以解决流出道梗阻，并可能降低进展风险。然而，目前很难准确预测哪些患者对干预有反应，并在出生时成为功能性双心室（BV），而不是成为功能性单心室（UV）。这种预测对于患者选择、家长咨询和手术计划都很重要。因此，我们研究了在一个回顾性队列中，基于胎儿前 FAV 图像的计算得出的生物力学参数是否可以可靠地区分具有 BV 或 UV 结局的 CAS-eHLHS 病例。为此，我们对 9 例接受干预的 CAS-eHLHS 病例和 6 例健康胎儿对照心脏进行了基于图像的有限元生物力学建模，并发现生物力学参数——收缩期肌纤维应力峰值——在 BV 和 UV 病例之间表现出独特的巨大差异，其效应比超声心动图参数更大。通过主成分分析，我们从超声测量值中推导出了一个简单的方程，用于快速简便地估计肌纤维应力。当在 37 例 CAS-eHLHS 病例的回顾性队列中进行测试时，该参数在预测 UV 与 BV 结局方面优于其他参数，因此如果将其纳入患者选择程序，具有改善结局预测的高潜力。从生理学上讲，高心肌应力可能表明心肌更健康，能够承受高应力并抵抗病理性重塑，这可以解释为什么它是 BV 结局的良好预测指标。要点：预测胎儿主动脉瓣狭窄伴进行性 HLHS 胎儿主动脉瓣成形术的形态学出生结局（单心室与双心室）对于准确的患者选择、家长咨询和管理决策非常重要。计算模拟表明，生物力学参数——介入前收缩期肌纤维最大应力——在区分这些结局方面具有独特的稳健性，优于所有超声心动图参数。开发了一个经验公式，可从常规超声测量值中快速计算收缩期肌纤维最大应力，并在测试的众多参数中是结局的最佳预测指标。
