Abstract
Upstream impedance could characterise the RV afterload and the relative contribution of large and small vessel disease in PH, regardless of the PAOP, including the inverse relationship with HR as an indirect RV functional response http://ow.ly/fqvN30nbNFo
To the Editor:
We read with great interest the recent article by Gerges et al. [1] on partitioning pulmonary vascular resistance (PVR) at baseline and after inhaled nitric oxide (iNO) in patients with pulmonary hypertension associated with left heart disease (PH-LHD). The study highlighted that the increase of right ventricular (RV) afterload in isolated post-capillary PH (Ipc-PH) primarily depended on a passive backward transmission of left ventricular filling pressure and left atrial (LA) function, explaining the very high upstream resistance (Rup). Further afterload increase secondary to an elevated vessel resistance in combined post- and pre-capillary pulmonary hypertension (Cpc-PH), was associated with a lower Rup similar to that seen in idiopathic pulmonary arterial hypertension (iPAH) patients.
Pulmonary vascular disease (PVD) in PH-LHD in patients with heart failure is associated with a prevalence of pulmonary veins, capillaries and distal muscular pulmonary arteries (PAs) remodelling [2, 3]. Current dogma suggests that decreased pulmonary arterial capacitance (PAC) in pulmonary hypertension (PH) is a consequence of distal proliferative PVD. We have shown that Ipc-PH patients with PVR and diastolic pulmonary gradient (DPG) within normal limits have a significant increase in area wall thickness and stiffening of proximal PA, and impairment of RV-to-pulmonary arterial coupling, suggesting the presence of early PVD and questioning the definition of “passive” PH-LHD [4]. We speculate that the presence of proximal PA wall disease in addition to the passive upstream transmission of elevated LA pressure may explain the significant lower PAC in Ipc-PH patients. The elevation of PVR and DPG would occur later with further reductions in PAC associated with distal PVD, as seen in Cpc-PH patients [4].
The definition of PH-LHD haemodynamic phenotypes is a matter of debate. The Ipc-PH and Cpc-PH phenotypes defined in the most recent 2015 ESC/ERS guidelines [5] have been challenged due to their controversial prognostic role and the ambiguous classification of a significant proportion of patients [6]. Both the stationary (PVR) and the pulsatile (PAC) components of afterload exhibit an inverse hyperbolic relationship. The product of resistance and compliance (RC-time) is mostly constant in both healthy and diseased states, with the exception of a few clinical scenarios like elevated left-sided filling pressures, proximal chronic thromboembolic PH (CTEPH) and heart rate (HR) increase. In all these cases, PAC decreases proportionally more than the increase in PVR, RC-time decreases and the R-C curve shifts downwards left [7, 8].
We have previously proposed an original dimensionless haemodynamic index, upstream impedance (Zup) ((TPG-DPG)/TPG) (where TPG is transpulmonary gradient), that enables the characterisation of the broad spectrum of dynamic afterload and predicts early outcome after pulmonary endarterectomy for CTEPH [9]. Replacing mean pulmonary arterial pressure (mPAP) with (sPAP+2dPAP)/3 (where sPAP and dPAP are systolic and diastolic PAP, respectively) in the numerator and with PVR×SV×HR+PAOP (where SV is systolic volume and PAOP is pulmonary arterial occlusion pressure, end-expiratory automated digital mean measurements across the cardiac cycle) in the denominator, Zup is inversely related to PAC, PVR, and HR:In PH states, the greater increase of pulsatile to the stationary component of RV afterload determines elevated PA pressures with a large pulse pressure or “ventricularisation” and higher Zup values [10]. We hypothesised that Zup could characterise the relative contribution of large and small vessels disease through its differential impact on the afterload components in PH states, regardless of the PAOP. We compare Zup values in patients with PH-LHD (post-capillary PH), and operable CTEPH and iPAH (pre-capillary PH).
We can see that Zup values are higher in post-capillary PH than pre-capillary PH, which is probably due to the greater pulsatile afterload associated with higher PAOP and lower HR. In pre-capillary PH, the more proximal occlusive site causes a higher PA stiffness and an earlier and greater wave reflection, increasing total PVR but with a lower dPAP and PAC and a higher Zup in operable CTEPH than in iPAH. Similarly, among post-capillary PH, the presence of proximal PVD determines the PAC decrease and the highest Zup in Ipc-PH patients. The elevation of PVR and DPG with more reductions in PAC associated with distal PVD, would explain the lower Zup of Cpc-PH than Ipc-PH. Despite the fact that the PA wall stiffness and the haemodynamic profile of Cpc-PH patients are very similar compared to historical patients with PAH, Zup is significantly higher, which is likely to be due to lower HR and the post-capillary condition (figure 1) [4, 11].
We observed substantial haemodynamic improvements in Cpc-PH patients after iNO administration [4] according to Gerges et al. [1]. The improved RV afterload with a concomitant 8% of Rup increase, indicates a decrease of distal PVR [1, 4].
Gerges et al. [1] proposed DPG as a surrogate of Rup, which is debatable, since while Rup corresponds to small PAs and arterioles resistances, DPG (>7 mmHg) defines the presence of PVD associated with the increase of pulsatile and/or stationary components of RV afterload.
In conclusion, Gerges et al. [1] have made an “in-depth” effort to link haemodynamics to PVD by partitioning the stationary component of the RV afterload in PH-LHD patients. We can speculate that Zup could provide a simple haemodynamic tool to characterise the different spectrum of RV afterload and the relative contribution of large and small vessel disease in PH states regardless of the PAOP, including the inverse relationship with HR as an indirect RV functional response.
Footnotes
Conflict of interest: J.C. Grignola has nothing to disclose.
Conflict of interest: P. Trujillo has nothing to disclose.
Conflict of interest: E. Domingo has nothing to disclose.
- Received October 4, 2018.
- Accepted December 4, 2018.
- Copyright ©ERS 2019