Pulmonary capillary wedge pressure augments right ventricular pulsatile loading

Abstract

Background: Right ventricular failure from increased pulmonary vascular loading is a major cause of morbidity and mortality, yet its modulation by disease remains poorly understood. We tested the hypotheses that, unlike the systemic circulation, pulmonary vascular resistance (R(PA)) and compliance (C(PA)) are consistently and inversely related regardless of age, pulmonary hypertension, or interstitial fibrosis and that this relation may be changed by elevated pulmonary capillary wedge pressure, augmenting right ventricular pulsatile load.

Methods and results: Several large clinical databases with right heart/pulmonary catheterization data were analyzed to determine the R(PA)-C(PA) relationship with pulmonary hypertension, pulmonary fibrosis, patient age, and varying pulmonary capillary wedge pressure. Patients with suspected or documented pulmonary hypertension (n=1009) and normal pulmonary capillary wedge pressure displayed a consistent R(PA)-C(PA) hyperbolic (inverse) dependence, C(PA)=0.564/(0.047+R(PA)), with a near-constant resistance-compliance product (0.48±0.17 seconds). In the same patients, the systemic resistance-compliance product was highly variable. Severe pulmonary fibrosis (n=89) did not change the R(PA)-C(PA) relation. Increasing patient age led to a very small but statistically significant change in the relation. However, elevation of the pulmonary capillary wedge pressure (n=8142) had a larger impact, significantly lowering C(PA) for any R(PA) and negatively correlating with the resistance-compliance product (P<0.0001).

Conclusions: Pulmonary hypertension and pulmonary fibrosis do not significantly change the hyperbolic dependence between R(PA) and C(PA), and patient age has only minimal effects. This fixed relationship helps explain the difficulty of reducing total right ventricular afterload by therapies that have a modest impact on mean R(PA). Higher pulmonary capillary wedge pressure appears to enhance net right ventricular afterload by elevating pulsatile, relative to resistive, load and may contribute to right ventricular dysfunction.

Figure 1

Pulmonary Vascular Resistance-Compliance Relationship. A) Pulmonary vascular resistance (R_PA) versus pulmonary arterial compliance (C_PA) in patients with known or suspected pulmonary hypertension (PH). The best fit curve is given by y=0.564/(0.047+x). B) Systemic arterial resistance (R_SA)-compliance (C_SA) relationship for the same patient cohort, with curve fit for pulmonary data also shown. C) RC time for pulmonary or systemic vasculature plot versus mean artery pressure. D) R_PA-C_PA relationship in patients with severe pulmonary fibrosis. The best fit hyperbolic decay for these patients (dotted) is compared to Cohort A result (gray solid line), and were identical.

Figure 2

Age Effect on Pulmonary Vascular Resistance-Compliance Relationship. A) Left Panel: R_PA-C_PA relationship, Right Panel: R_SA-C_SA relationship. Data are sub-grouped (color coding) into three age tertiles. Dashed lines identify tertiles for compliance and resistance based on these data. B) Percentage of patients within each age tertile separated among tertiles for compliance or resistance in pulmonary or systemic arteries, respectively. P-values are for cross-tabulation analysis, χ² test. See text for details.

Figure 3

Effect of Elevated PCWP on Pulmonary Vascular Resistance-Compliance Relationship. A) R_PA-C_PA relationship from two subgroups of Cohort C, those with normal range or elevated PCWP. Gray line is best fit curve from Figure 1A (Cohort A). B) Log(R_PA)−Log(C_PA) plot (n=4735), color coded into five subgroups based on PCWP; p<0.001) C) Mean RC time for each PCWP sub-group versus PCWP.

Figure 4

Effect of R_PA-C_PA relationship by change in PCWP within an individual patient. A) R_PA-C_PA for each patient is plot at two different study times, one when the patient had a low (PCWP≤10 mmHg) and the other a high PCWP (PCWP ≥ 20mmHg). B) Effect of increasing PCWP during supine exercise on R_PA-C_PA in 24 patients with early heart failure with preserved ejection fraction.

Figure 5

Effect of PH treatment on R_PA-C_PA data. The curve fit from Cohort A (PH/SPH) is shown, and superimposed on it are mean pre- and post-treatment R_PA and C_PA derived from three PH therapeutic trials involving sildenafil, treprostinil, or prostacyclin^– . There was high resting R_PA and low C_PA and only modest decline in R_PA with treatment; thus C_PA remained low and so pulsatile load remained high after therapy.