After nearly half a century, there has been broad acceptance that the systemic arterial circulation combines a resistive and capacitive load, and that these can vary at least partially independent of one another. The pulmonary vasculature is very different, coupling resistance and compliance in a very constrained manner so long as pulmonary venous pressure is low. Increasing PCWP appears to alter this behavior to augment right heart pulsatile load. The current study establishes key properties for right heart-pulmonary vascular coupling and illustrates a previously unappreciated deleterious impact of left heart pressures on pulsatile RV load. This is important, as right ventricular dysfunction is a major independent predictor of death from cardiac and/or pulmonary vascular disease.10–13
It has previously been shown that the RPA
relation does not change with treatment of PH.5
The consistency and shape of the RPA
relation, which our study confirms in large patient groups with normal-range PCWP, have important clinical implications. The relationship’s overall predictability means that a simple set of RHC data defines a given patient’s position on a shared continuum curve, allowing one to possibly predict a therapeutic target. Based on this relation, clinicians may be able to estimate how much RPA
must be lowered to have any meaningful change in CPA
, and thus, pulsatile (and net) afterload. It also indicates that unlike the proximal aorta in the systemic circulation, the main pulmonary artery adds relatively little to overall pulmonary vascular compliance, since if the PA stiffened independent of resistance with PH, the RC time would decline. This is further supported by work of Saouti et al6
, who determined that proximal pulmonary arteries contribute only 19% to overall compliance and that, unlike systemic arteries, pulmonary vascular compliance is distributed evenly throughout the peripheral lung in conjunction with resistance. Small age-dependent changes in CPA
also support this notion and are consistent with little rise in pulse wave velocity from the main PA to peripheral lung with aging.14
While some change in main PA distensibility can occur with disease or age, this is small and has less impact on RV load than what is determined by the peripheral vessels. The flatness of the curve at elevated RPA
means that resistance must decline substantially to meaningfully impact net RV loading, since pulmonary compliance would still be quite low. This was first suggested by Lankhaar et al4
, and may underscore why hemodynamic measurements including RPA
have been generally unreliable endpoints for clinical PH management.15
One can appreciate this problem by plotting the average pre- and post- treatment RPA
from three large therapeutic PH trials involving sildenafil, treprostinil, or prostacyclin ().16–18
A high baseline RPA
(0.62,0.77, or 0.96 mmHg*S*mL−1
respectively) and modest decline with treatment (0.50, 0.71, 0.63 mmHg*S*mL−1
, respectively) would mean little to no change in estimated compliance, thus maintaining a high RV pulsatile load. While these therapies are clinically used, one would anticipate more effective treatment would need to reduce RPA
further or differentially enhance CPA
to also impact pulsatile load.
Figure 5 Effect of PH treatment on RPA-CPA data. The curve fit from Cohort A (PH/SPH) is shown, and superimposed on it are mean pre- and post-treatment RPA and CPA derived from three PH therapeutic trials involving sildenafil, treprostinil, or prostacyclin16– (more ...)
The RPA-CPA relation’s sensitivity to pulmonary venous pressure introduces a new way of considering the hemodynamic consequences of elevated left-sided filling pressures. We initially considered that a high PCWP might impact parenchymal stiffness, with the lung acting as more of a wet than dry sponge. Distensibility of small vessels in the lung tissue is enhanced when surrounded by compressible air, but this would be diminished if the parenchyma stiffened. One counter to this theory is the data showing severe pulmonary fibrosis does not generate the same effect. An alternative is that PCWP is the downstream pressure that amplifies a peripheral pulse reflection, thereby augmenting systolic pulmonary arterial pressure (PAP) and leading to a decline in total compliance.
The impact of PCWP on pulmonary arterial and thus right heart loading is likely relevant to clinical symptoms in heart failure patients. Such individuals become dyspneic during exercise when PCWP frequently rises. Lewis et al19
recently showed that symptoms and clinical outcomes of patients with LV dysfunction correlate better with augmentation in PAP than the change in PCWP. At first glance, this may seem in contrast to the findings in this study. However, we would suggest this observation could be explained by the effect of PCWP on the RPA
relationship. Elevations in PCWP lowers CPA
for a given RPA
, resulting in enhanced pulmonary arterial wave reflections and augmentation of the systolic PAP, and thus, mean PAP. Therefore, the higher proportional rise in mean PAP compared to PCWP could be explained by the indirect effect of rising PCWP lowering CPA
. Our findings also indicate that with the rise in PCWP, there will be enhanced pulsatile RV load, which would further limit RV ejection, and in turn LV filling. Indeed, in the patients in whom mean PAP augmentation plateaued during exercise (indicating RV dysfunction), prognosis was worse.
Our study has several limitations. We relied on the recorded clinical indication for RHC for identifying patients with suspected PH or known PH, and while the actual diagnosis was more mixed and indeed some did not have PH, the consistency of the RPA
relation despite this further supports the idea of its constancy so long as PCWP is in the normal range. Similarly for all cohorts, we relied on the original operator’s recordings and interpretation of hemodynamic data. It is possible that interpretations of tracings may have been different among individual operators. However, the primary data were all interpreted by heart failure cardiologists or pulmonologists, and our blinded review found minimal inter-observer error on a random subset of studies. Lastly, we relied on an indirect estimate of total pulmonary vascular compliance. Alternative approaches using pulsatile pressure-flow analysis are difficult and impractical for large population studies, but the estimation method has favorably compared to such alternative approaches in smaller controlled studies.1–3,4
In conclusion, the pulmonary circulation and the afterload it imposes on the RV are very different from the systemic circulation. PH, interstitial fibrosis, and patient age do not appear to have much effect on the inverse, hyperbolic RPA-CPA relationship. Because of the consistency of this relationship, one can estimate pulmonary vascular compliance from resistance using a simple equation, identify where a given patient lies relative to normal, and possibly anticipate what therapy would need to achieve for a robust clinical benefit. The findings that a higher PCWP may impact pulmonary arterial and thus RV pulsatile loading offers new insight into the symptomatology of HFpEF and other left heart failure disorders.