Proximal pulmonary arterial remodeling impairs right ventricular-arterial coupling in postcapillary pulmonary hypertension patients

to the editor: The study by Oakland et al. (1) integrates the static and pulsatile components of afterload on right ventricular (RV) function in pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF). However, there are two main points that we would like to argue.

The authors have reported that RV-arterial (RV-PA) uncoupling (Ees/Ea, end-systolic ventricular elastance to arterial elastance ratio) in PH-HFpEF appears to be independent of afterload, suggesting a predominant role of RV cardiomyopathy. Although certain RV features in PH-HFpEF (early decrease in radial shortening and late homeometric adaptation) (2) could explain the inherent abnormality of the RV myocardium proposed by the authors, it is counterintuitive to explain a similar RV-PA uncoupling in both Ipc-PH and Cpc-PH with a preserved Zc and arterial elastance in the former. Beyond the load dependence of the TAPSE/sPAP (tricuspid annular plane systolic excursion normalized by pulmonary artery systolic pressure) ratio, it has been proposed as a surrogate of the gold standard invasive Ees/Ea ratio (3). Gorter et al. (4) have shown that abnormal TAPSE/sPAP identified patients with PH-HFpEF with a precapillary component and predicted poor outcomes. Accordingly, we have reported a more preserved TAPSE/sPAP in patients with Ipc-PH versus patients with Cpc-PH with persistent pulmonary hypertension after successful left-sided valve replacement (5).

The authors have suggested the lack of advanced proximal PA remodeling in Ipc-PH because they did not have a high characteristic impedance (Zc). Various stiffness assessments (S) have the general equation

$$\text{S}\hspace{0.17em}\sim \surd (\text{Eh}/{\text{r}}^{\text{x}})$$

where the product of elastic modulus (E) and wall thickness (h) is divided by lumen radius (r) raised to a power (x) that depends on the stiffness parameter. Zc has a fivefold dependence on vessel diameter; therefore, when the central artery remodels to a larger diameter, it is possible for Zc to remain unchanged or decline because the increase in lumen radius has a more significant relative effect on Zc than the increase in E (6). Adequate stiffness of the PA is vital for appropriate matching between the RV and its load. Stevens et al. (7) reported that PA stiffness is independently associated with the RV dysfunction in PH. We showed that even patients with Ipc-PH with normal pulmonary vascular resistance (PVR) values have a significant proximal PA wall disease (raise in area wall thickness and E), suggesting the presence of early PA wall remodeling and questioning the definition of “passive” PH associated with left heart disease (PH-LHD) (5). We speculate that the presence of proximal PA remodeling, in addition to the upstream transmission of elevated left atrial pressure, could explain the significant lower pulmonary capacitance and impairment of RV-PA coupling despite normal PVR value in patients with Ipc-PH (8, 9). The early proximal PA wall remodeling associated with the impairment of RV-PA coupling and the parallel effect of the left ventricle to RV (interventricular septum) could explain the absence of association of the distal pulmonary vascular remodeling with RV dysfunction in PH-LHD (10).

Undoubtedly, the type of LHD (HFpEF, HF-reduced EF, and valvular heart disease) and the hemodynamic phenotype (Ipc-PH and Cpc-PH) must be considered to better understand the response of the RV-PA unit in patients with PH-LHD.

DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the authors.

AUTHOR CONTRIBUTIONS

J.C.G. and P.T. drafted manuscript; J.C.G. edited and revised manuscript; J.C.G. and P.T. approved final version of manuscript.