Pulmonary Capillary Wedge Pressure Augments Right Ventricular Pulsatile Loading

Division of Cardiology, Johns Hopkins Medical Institutions, Ross 858, 720 Rutland Ave, Baltimore, MD 21205, USA.
Circulation (Impact Factor: 14.43). 11/2011; 125(2):289-97. DOI: 10.1161/CIRCULATIONAHA.111.051540
Source: PubMed


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.
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).
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.

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    • "This difference remains true if RHCs with negative DPGs are included as well. The inverse relationship between PVR and Ca proposed by Tedford et al. (with an indicator function added for the PAH group) when applied to our data was similar to our own best fitted (inverse) model (residual errors 0.697 and 0.696, respectively) (Tedford et al. 2012). Therefore, we validate and use the model proposed by Tedford et al. "
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    ABSTRACT: Pulmonary vascular resistance (PVR) is traditionally used to describe pulmonary hemodynamic characteristics. However, it does not take into account pulmonary artery compliance (Ca) or pulsatile flow. The product of PVR and Ca is known as RC time. Previous studies assert that the PVR-Ca relationship is fixed and RC time is constant between health and disease states. We hypothesized that RC time was not constant in health and pulmonary vascular disease. Right heart catheterizations performed in Papworth Hospital over a 6 year period were analyzed. Subjects were divided into those with normal pulmonary hemodynamics (NPH group; n = 156) and pulmonary arterial hypertension (PAH group; n = 717). RC time and the right ventricle (RV) oscillatory power fraction were calculated. RC time for the NPH group (0.47 ± 0.13 sec) is significantly lower than the PAH group (0.56 ± 0.16 sec; P < 0.0001). The RV oscillatory power fraction is lower in the NPH group (P < 0.0001). RC time correlates inversely with the RV oscillatory power fraction in each group. We conclude, there is an inverse relationship between PVR and Ca, however, this relationship is not always fixed. Consequently, RC time is significantly lower in health compared to disease with elevated pulmonary artery pressures. PAH leads to a decrease in cardiac efficiency. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
    04/2015; 3(4). DOI:10.14814/phy2.12363
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    • "In a series of relatively small studies, different authors stated that RC is nearly constant [4]. Tedford et al. [5] have recently challenged the concept of a fixed RC in PH due to left heart failure. Most of the studies which have compared pulsatile afterload properties in pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH), with small number of patients and significant different mean arterial pressure (mP), have observed contradictory results [3] [6]. "
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    ABSTRACT: Pulsatile afterload describes the compliance (Cp) of the pulmonary artery (PA) and the coupling of the right ventricle (RV) contraction to the PA afterload. Recent studies have demonstrated the important role of pulsatile afterload in the progression of RV impairment and the prognostic value of Cp in pulmonary hypertension (PH). Previous studies have observed that pulmonary vascular resistance (PVR) and Cp are coupled via an inverse linear relationship (RC). There is an unsolved controversy about the role that the site of the obstruction in the pulmonary vascular bed plays on this RC relationship. In a series of relatively small studies, different authors stated that RC is nearly constant. Tedford et al. have recently challenged the concept of a fixed RC in PH due to left heart failure. Most of the studies which have compared pulsatile afterload properties in pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH),with small number of patients and significant different mean arterial pressure (mP), have observed contradictory results. Recent studies have shown that the RC time can be shorter in CTEPH caused by proximal obstruction compared to distal obstruction. Nevertheless there is currently no feasiblemethod in clinical practice to determine the real amount of obstruction in the distal pulmonary arteries and this discrimination of proximal and distal obstruction in the classification of CTEPH has been abandoned in the current PH guidelines. We hypothesized that the different distribution of the vascular remodeling in PAH and CTEPH impacts on RC time independently of mP. The aim of this study was to compare the hemodynamic pulsatile afterload in a large population of PAH and CTEPH patients.
    International Journal of Cardiology 02/2015; 181(1):232-234. DOI:10.1016/j.ijcard.2014.11.118 · 4.04 Impact Factor
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    • "Proximal stiffness has been shown to (1) regulate pressure and flow wave velocities in the pulmonary bed [20]; (2) affect afterload independent of resistance [21]; and (3) affect proximal wall shear stress (WSS) and thus potentially have impacts on cellular signaling through mechanotransduction [3]. Recent studies on the arterial compliance show that increased PVR correlates to decreased arterial compliance, which establishes a constant [22, 23] or shorten resistance-compliance time [24–26] during PH progression. The decrease in compliance, such as the proximal stiffening is also important and affects the entire vasculature, as well as increased right ventricular (RV) afterload [27, 28]. "
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    ABSTRACT: We develop a simple computational model based on measurements from a hypoxic neonatal calf model of pulmonary hypertension (PH) to investigate the interplay between vascular and ventricular measures in the setting of progressive PH. Model parameters were obtained directly from in vivo and ex vivo measurements of neonatal calves. Seventeen sets of model-predicted impedance and mean pulmonary arterial pressure (mPAP) show good agreement with the animal measurements, thereby validating the model. Next, we considered a predictive model in which three parameters, PVR, elastic modulus (EM), and arterial thickness, were varied singly from one simulation to the next to study their individual roles in PH progression. Finally, we used the model to predict the individual impacts of clinical (vasodilatory) and theoretical (compliance increasing) PH treatments on improving pulmonary hemodynamics. Our model (1) displayed excellent patient-specific agreement with measured global pulmonary parameters; (2) quantified relationships between PVR and mean pressure and PVS and pulse pressure, as well as studiying the right ventricular (RV) afterload, which could be measured as a hydraulic load calculated from spectral analysis of pulmonary artery pressure and flow waves; (3) qualitatively confirmed the derangement of vascular wall shear stress in progressive PH; and (4) established that decreasing proximal vascular stiffness through a theoretical treatment of reversing proximal vascular remodeling could decrease RV afterload.
    Computational and Mathematical Methods in Medicine 11/2013; 2013:618326. DOI:10.1155/2013/618326 · 0.77 Impact Factor
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