Predicting Patient Status in Chronic Thromboembolic Pulmonary Hypertension Using a Biophysical Model.

Chronic thromboembolic pulmonary hypertension (CTEPH) involves abnormally high blood pressure in the pulmonary vessels and is associated with small vessel vasculopathy and pre-capillary proximal occlusions. Management of CTEPH disease is challenging, therefore accurate diagnosis is crucial in ensuring effective treatment and improved patient outcomes. The treatment of choice for CTEPH is pulmonary endarterectomy, which is an invasive surgical intervention to remove thrombi. Following PEA, a number of patients experience poor outcomes or worse-than-expected improvements, which may indicate that they have significant small vessel disease. A method that can predict the extent of distal remodelling may provide useful clinical information to plan appropriate CTEPH patient treatment. Here, a novel biophysical modelling approach has been developed to estimate and quantify the extent of distal remodelling. This method includes a combination of mathematical modelling and computed tomography pulmonary angiography to first model the geometry of the pulmonary arteries and to identify the under-perfused regions in CTEPH. The geometric model is then used alongside haemodynamic measurements from right heart catheterisation to predict distal remodelling. In this study, the method is tested and validated using synthetically generated remodelling data. Then, a preliminary application of this technique to patient data is shown to demonstrate the potential of the approach for use in the clinical setting.Clinical relevance- Patient-specific modelling can help provide useful information regarding the extent of distal vasculopathy on a per-patient basis, which remains challenging. Physicians can be unsure of outcomes following pulmonary endarterectomy. Therefore, the predictive aspect of the patient's response to surgery can help with clinical decision-making.

An in silico approach to understanding the interaction between cardiovascular and pulmonary lymphatic dysfunction.

The lung is extremely sensitive to interstitial fluid balance, yet the role of pulmonary lymphatics in lung fluid homeostasis and its interaction with cardiovascular pressures is poorly understood. In health, there is a fine balance between fluid extravasated from the pulmonary capillaries into the interstitium and the return of fluid to the circulation via the lymphatic vessels. This balance is maintained by an extremely interdependent system governed by pressures in the fluids (air and blood) and tissue (interstitium), lung motion during breathing, and the permeability of the tissues. Chronic elevation in left atrial pressure (LAP) due to left heart disease increases the capillary blood pressure. The consequent fluid accumulation in the delicate lung tissue increases its weight, decreases its compliance, and impairs gas exchange. This interdependent system is difficult, if not impossible, to study experimentally. Computational modeling provides a unique perspective to analyze fluid movement in the cardiopulmonary vasculature in health and disease. We have developed an initial in silico model of pulmonary lymphatic function using an anatomically structured model to represent ventilation and perfusion and underlying biophysical laws governing fluid transfer at the interstitium. This novel model was tested against increased LAP and noncardiogenic effects (increased permeability). The model returned physiologically reasonable values for all applications, predicting pulmonary edema when LAP reached 25 mmHg and with increased permeability.NEW & NOTEWORTHY This model presents a novel approach to understanding the interaction between cardiac dysfunction and pulmonary lymphatic function, using anatomically structured models and biophysical equations to estimate regional variation in fluid transport from blood to interstitial and lymphatic flux. This fluid transport model brings together advanced models of ventilation, perfusion, and lung mechanics to produce a detailed model of fluid transport in health and various altered pathological conditions.