Pulmonary Capillary Wedge Pressure Augments Right Ventricular Pulsatile Loading

Abstract

Background Right ventricular (RV) 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 (RPA) and compliance (CPA) are consistently and inversely related regardless of age, pulmonary hypertension (PH), or interstitial fibrosis, and that this relation may be changed by elevated pulmonary capillary wedge pressure (PCWP), augmenting RV pulsatile load. Methods and Results Several large clinical databases with right heart/pulmonary catheterization data were analyzed to determine the RPA-CPA relationship with PH, pulmonary fibrosis, patient age, and varying PCWP. Patients with suspected or documented PH (n=1009) and normal PCWP displayed a consistent RPA-CPA hyperbolic (inverse) dependence; CPA=0.564/(0.047+RPA), with a near constant resistance-compliance product (RC) (0.48±0.17 seconds). In the same patients, the systemic RC was highly variable. Severe pulmonary fibrosis (n=89) did not change the RPA-CPA relation. Increasing patient age led to a very small though statistically significant change in the relation. However, elevation of the PCWP (n=8142) had a larger impact, significantly lowering CPA for any RPA, and negatively correlating RC (p<0.0001). Conclusions PH and pulmonary fibrosis do not significantly change the hyperbolic dependence between RPA and CPA, while patient age has only minimal affects. This fixed relationship helps explain the difficulty of reducing total RV afterload by therapies that have modest impact on mean RPA. Higher PCWP appears to enhance net RV afterload by elevating pulsatile, relative to resistive load, and may contribute to RV dysfunction.

Acute hemodynamic effects of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction

“…This observation provides further physiological support for the role of exogenous administration of sodium nitrite for nonGroup 1 PH patients. Tedford et al demonstrated that elevated pulmonary capillary wedge pressure was associated with lower Cpa for any given PVR (shifting the resistance-compliance curve down and to the left), although there is still some debate about this in the literature (25,32). We found no difference in the baseline resistance-compliance relationship between patient groups.…”

“…Treatment effects are presented as mean values and their 95% confidence intervals. Resistance-compliance curves were constructed and the data were fit to an inverse hyperbolic curve and compared using the extra sum-of-squares F test (Prism 6, GraphPad Software) (25). Statistical significance was defined as a 2-sided P value less than 0.05.…”

Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction

“…24 Tedford et al have shown that increases in PCWP are associated with lower PA compliance at any given resistance, increasing the oscillatory load on the RV, and this effect occurs even acutely during exercise in patients with HFpEF. 78 Because they are connected in series, inadequate RV output could contribute to exercise limitation by promoting "underfilling" of the left heart during stress. Although this phenomenon has been demonstrated in HFrEF, 79 it has not been documented in patients with HFpEF.…”

Pulmonary Hypertension in Heart Failure Preserved Ejection Fraction

“…These main hemodynamic alterations expose the lung vasculature to pressure-induced challenges whose most immediate acute threat is pulmonary edema. 4 In the long term, the sustained backward hemodynamic transmission, along with the potential contribution of mitral insufficiency, increases the pulsatile loading on the right ventricle (RV) 5 and triggers pulmonary hypertension (PH) development and symptom exacerbation. 6 Thus, as a consequence of hemodynamic and functional perturbations, PH-HFpEF develops as a more advanced corollary of diastolic HF, leading to abnormal phenotypes of the lung microcirculation, 7,8 the arterial system, and right heart function 9-11 ( Figure 1).…”