Assessment of compliance in pulmonary arterial hypertension

The main mechanical feature of the pulmonary circulation is the ability to sustain low pressure levels even in the presence of high flow,1 thus being defined as a low resistance/high compliance system. Pulmonary hypertension is a multifactorial clinical condition mainly characterized by vascular remodelling that increases right ventricular afterload, eventually leading to ventricular dysfunction.2 Most of the clinical presentation and haemodynamic behaviour is directly related to the development and progression of right heart failure. Usually, this increase in afterload is described as the increase in pulmonary vascular resistance (PVR); indeed, PVR is one of the components of the right ventricular afterload. However, the total afterload is determined by three different vascular characteristics: resistance, compliance, and impedance.3 Whilst the concept of impedance is a little more difficult to transpose to the clinical setting, once it accounts the inertial properties of blood flow, resistance and compliance can be easily assimilated, even though, in the setting of pulmonary hypertension, most of the attention has been paid to the former only.4 PVR simply reflects a ratio of a mean pressure level and a mean flow through the pulmonary circulation, where the flow is frequently accepted as the total cardiac output. This calculation assumes a steady flow, thus completely ignoring the pulsatile load imposed by the cardiac cycle.5 The buffering of the pulsatile load takes us directly to the concept of vascular compliance, reinforcing the important physiological information that may derive from its study, particularly in the setting of a condition characterized by vascular remodelling such as pulmonary arterial hypertension (PAH). Among many different available techniques to assess vascular compliance, the ratio of stroke volume and pulse pressure seems to be the simplest one, in terms of clinical applicability, taking into consideration that it may overestimate arterial compliance.6 The reason for this overestimation relies on the fact that this method assumes that the entire stroke volume is buffered within the arterial component of the pulmonary circulation therefore ignoring the arterial outflow volume that is buffered within the capillaries and thereafter. Nevertheless, this method for the estimation of pulmonary arterial compliance has already been shown to reflect survival in PAH.7 Lankhaar and associates have nicely demonstrated that the product of PVR and compliance remains constant over time.8 The same group had already demonstrated that plotting compliance against resistance, derived from patients both with and without pulmonary hypertension, and thus under different haemodynamic conditions, results in a hyperbola that reflects the coupling of these two components of right ventricular afterload.9 More interestingly, in the present work, they showed that this coupling of resistance and compliance is not affected by specific therapy in PAH patients.8 This finding is significantly relevant since it suggests that PAH may comply with this coupling throughout its course, from early disease to end-stage disease. This not only suggests that a decrease in vascular compliance may be as important as an increase in vascular resistance but also infers that during the early phase of pulmonary hypertension, the decrease in compliance may be the most important haemodynamic feature. Some indirect findings strengthen the importance of vascular compliance. Recently, the same group has measured pulmonary arterial stiffness through magnetic resonance imaging (MRI) in patients with PAH, showing that the greater the variation of the pulmonary artery cross-sectional area during the cardiac cycle, the better was the survival.10 The same concept had been previously used in another MRI study, showing that PAH patients that acutely responded to nitric oxide inhalation had higher pulmonary artery distensibility.11 One could easily extrapolate the findings from the study of Lankhaar et al.8 to explain the presence of exercise-induced pulmonary hypertension in symptomatic patients with normal baseline haemodynamics. Possibly, the increased cardiac output during exercise associated with the decreased pulmonary vascular compliance would expose the vascular remodelling not revealed by a normal or slightly increased baseline PVR. However, this hypothesis should be interpreted with caution if it implies that this population of exercise-induced pulmonary hypertension patients would develop pulmonary hypertension at rest with progression of the vascular remodelling process, which has not been demonstrated so far. Nevertheless, this speculation clearly illustrates the perspective of monitoring pulmonary vascular compliance in the clinical setting. Indeed, previous studies have addressed the importance of the time constants from the different vascular compartments of the pulmonary circulation12 as well as the role of haemodynamic evaluation during exercise in evidencing the true coupling between pressure and flow in PAH patients.13 Taking these previous findings into consideration, the study of Lankhaar et al.8 raises the question of how the coupling between resistance and compliance will behave during exercise or facing other stimuli that may greatly increase cardiac output. Reinforcing the concept of pulmonary vascular compliance and demonstrating its sustained coupling with PVR throughout the disease course, Lankhaar et al. have highlighted the need to follow compliance as a surrogate marker in PAH. Conflict of interest: none declared.