Pulmonary vascular resistance and compliance stay inversely related during treatment of pulmonary hypertension.

AIMS: Pulmonary arterial compliance (C) is increasingly being recognized as an important contributor to right ventricular afterload, but for monitoring of treatment of pulmonary hypertension (PH) most often still only pulmonary vascular resistance (R) is used. We aimed at testing the hypothesis that R and C are coupled during treatment of PH and that substantial changes in both R and C would result in more haemodynamic improvement than changes in R alone. METHODS AND RESULTS: Data were analysed of two right-heart catheterizations of 52 patients with pulmonary arterial hypertension and 10 with chronic-thromboembolic PH. The product of R and C (= stroke volume over pulse pressure) did not change during therapy (P = 0.320), implying an inverse relationship. Changes in cardiac index correlated significantly (P < 0.001) with changes in R (R(2) = 0.37), better with changes in C (R(2) = 0.66), and best with changes in both (R(2) = 0.74). CONCLUSION: During therapy for PH, R and C remain inversely related. Therefore, changes in both R and C better explain changes in cardiac index than either of them alone. Not only resistance but also compliance plays a prominent role in PH especially in an early stage of the disease.

Noninvasively assessed pulmonary artery stiffness predicts mortality in pulmonary arterial hypertension.

AIMS: Decreased total compliance of the pulmonary vascular bed is associated with increased mortality in patients with pulmonary arterial hypertension (PAH). We investigated whether proximal pulmonary artery stiffness, in terms of area distensibility and noninvasively assessed relative area change (RAC), calculated as relative cross-sectional area change, predicts mortality in patients with PAH. METHODS AND RESULTS: Eighty-six subjects underwent right-heart catheterization and MRI to assess area distensibility and RAC. Patients were followed up to 48 months. Kaplan-Meier plot and Cox proportional hazards regression analyses assessed the predictive value of area distensibility and RAC. In 70 patients, the diagnosis PAH was confirmed, and 16 subjects served as control subjects. In comparison with control subjects, proximal pulmonary arteries of patients were distended (685 +/- 214 mm2 vs 411 +/- 153 mm2, p < 0.001), less distensible (area distensibility = 0.46 +/- 0.38.10(-2) mm Hg(-1) vs 3.69 +/- 1.96.10(-2) mm Hg(-1), p < 0.0001), and RAC was smaller (20 +/- 10% vs 58 +/- 21%, p < 0.0001) [mean +/- SD]. RAC showed an inverse curvilinear relation with mean pulmonary artery pressure (R2 = 0.47). Eighteen patients (26%) died because of cardiopulmonary causes. Patients with a pulmonary artery RAC 16% (log-rank p < 0.001). RAC predicted mortality better than area distensibility. CONCLUSION: Noninvasively measured pulmonary artery RAC predicts mortality in patients with PAH.

Estimation of three- and four-element windkessel parameters using subspace model identification.

A windkessel model is widely used to operationalize vascular characteristics. In this paper, we employ a noniterative subspace model identification (SMI) algorithm to estimate parameters in a three- and four-element windkessel model by application of physical foreknowledge. Simulation data of the systemic circulation were used to investigate systematic and random errors in the parameter estimations. Results were compared with different methods as proposed in the literature: one closed-loop and two iterative methods for the three-element model, and one iterative method for the four-element model. For the three-element model, no significant systematic errors were observed using SMI. Concerning random errors, SMI appeared more robust in parameter estimations compared with the other methods (P < 0.05 for a signal-to-noise ratio of 18 dB). For the four-element model, a significant systematic error in the estimate of the arterial inertance L was observed (P = 0.011). However, for all methods, an increasing number of outliers in parameter estimates were observed at increased noise levels. These outliers were almost exclusive due to errors in estimates of L. In conclusion, with SMI physical parameters can mathematically be derived by application of physiological foreknowledge. For a three-element windkessel model, SMI appeared a very robust method to estimate parameters. However, application to a four-element windkessel model was less accurate because of low identifiability of L. Therefore, based on the simulation results, the use of the four-element windkessel model is questionable.

The arterial Windkessel.

Frank's Windkessel model described the hemodynamics of the arterial system in terms of resistance and compliance. It explained aortic pressure decay in diastole, but fell short in systole. Therefore characteristic impedance was introduced as a third element of the Windkessel model. Characteristic impedance links the lumped Windkessel to transmission phenomena (e.g., wave travel). Windkessels are used as hydraulic load for isolated hearts and in studies of the entire circulation. Furthermore, they are used to estimate total arterial compliance from pressure and flow; several of these methods are reviewed. Windkessels describe the general features of the input impedance, with physiologically interpretable parameters. Since it is a lumped model it is not suitable for the assessment of spatially distributed phenomena and aspects of wave travel, but it is a simple and fairly accurate approximation of ventricular afterload.

Cardiac phase-dependent time normalization reduces load dependence of time-varying elastance.

The time-varying elastance concept provides a comprehensive description of the intrinsic mechanical properties of the left ventricle that are assumed to be load independent. Based on pressure-volume measurements obtained with combined pressure conductance catheterization in six open-chest anesthetized sheep, we show that the time to reach end systole (defined as maximal elastance) is progressively prolonged for increasing ventricle pressures, which challenges the original (load-independent) time-varying elastance concept. Therefore, we developed a method that takes into account load dependency by normalization of time course of the four cardiac phases (isovolumic contraction, ejection, isovolumic relaxation, filling) individually. With this normalization, isophase lines are obtained that connect points in pressure-volume loops of different beats at the same relative time in each of the four cardiac phases, instead of isochrones that share points at the same time in a cardiac cycle. The results demonstrate that pressure curves can be predicted with higher accuracy, if elastance curves are estimated using isophase lines instead of using isochrones [root-mean-square error (RMSE): 3.8 +/- 1.0 vs. 14.0 +/- 7.4 mmHg (P < 0.001), and variance accounted for (VAF): 94.8 +/- 1.3 vs. 78.6 +/- 14.8% (P < 0.001)]. Similar results were found when the intercept volume was assumed to be time varying [RMSE: 1.7 +/- 0.3 vs. 13.4 +/- 7.4 mmHg (P < 0.001), and VAF: 97.4 +/- 0.5 vs. 81.8 +/- 15.5% (P < 0.001)]. In conclusion, phase-dependent time normalization reduces cardiac load dependency of timing and increases accuracy in estimating time-varying elastance.

Modeling the instantaneous pressure-volume relation of the left ventricle: a comparison of six models.

Simulations are useful to study the heart's ability to generate flow and the interaction between contractility and loading conditions. The left ventricular pressure-volume (PV) relation has been shown to be nonlinear, but it is unknown whether a linear model is accurate enough for simulations. Six models were fitted to the PV-data measured in five sheep and the estimated parameters were used to simulate PV-loops. Simulated and measured PV-loops were compared with the Akaike information criterion (AIC) and the Hamming distance, a measure for geometric shape similarity. The compared models were: a time-varying elastance model with fixed volume intercept (LinFix); a time-varying elastance model with varying volume intercept (LinFree); a Langewouter's pressure-dependent elasticity model (Langew); a sigmoidal model (Sigm); a time-varying elastance model with a systolic flow-dependent resistance (Shroff) and a model with a linear systolic and an exponential diastolic relation (Burkh). Overall, the best model is LinFree (lowest AIC), closely followed by Langew. The remaining models rank: Sigm, Shroff, LinFix and Burkh. If only the shape of the PV-loops is important, all models perform nearly identically (Hamming distance between 20 and 23%). For realistic simulation of the instantaneous PV-relation a linear model suffices.

Quantification of right ventricular afterload in patients with and without pulmonary hypertension.

Right ventricular (RV) afterload is commonly defined as pulmonary vascular resistance, but this does not reflect the afterload to pulsatile flow. The purpose of this study was to quantify RV afterload more completely in patients with and without pulmonary hypertension (PH) using a three-element windkessel model. The model consists of peripheral resistance (R), pulmonary arterial compliance (C), and characteristic impedance (Z). Using pulmonary artery pressure from right-heart catheterization and pulmonary artery flow from MRI velocity quantification, we estimated the windkessel parameters in patients with chronic thromboembolic PH (CTEPH; n = 10) and idiopathic pulmonary arterial hypertension (IPAH; n = 9). Patients suspected of PH but in whom PH was not found served as controls (NONPH; n = 10). R and Z were significantly lower and C significantly higher in the NONPH group than in both the CTEPH and IPAH groups (P < 0.001). R and Z were significantly lower in the CTEPH group than in the IPAH group (P < 0.05). The parameters R and C of all patients obeyed the relationship C = 0.75/R (R(2) = 0.77), equivalent to a similar RC time in all patients. Mean pulmonary artery pressure P and C fitted well to C = 69.7/P (i.e., similar pressure dependence in all patients). Our results show that differences in RV afterload among groups with different forms of PH can be quantified with a windkessel model. Furthermore, the data suggest that the RC time and the elastic properties of the large pulmonary arteries remain unchanged in PH.

Impaired left ventricular filling due to right-to-left ventricular interaction in patients with pulmonary arterial hypertension.

The aim of this study was to investigate the contribution of direct right-to-left ventricular interaction to left ventricular filling and stroke volume in 46 patients with pulmonary arterial hypertension (PAH) and 18 control subjects. Stroke volume, right and left ventricular volumes, left ventricular filling rate, and interventricular septum curvature were measured by magnetic resonance imaging and left atrial filling by transesophageal echocardiography. Stroke volume, left ventricular end-diastolic volume, and left ventricular peak filling rate were decreased in PAH patients compared with control subjects: 28 +/- 13 vs. 41 +/- 10 ml/m(2) (P < 0.001), 46 +/- 14 vs. 61 +/- 14 ml/m(2) (P < 0.001), and 216 +/- 90 vs. 541 +/- 248 ml/s (P < 0.001), respectively. Among PAH patients, stroke volume did not correlate to right ventricular end-diastolic volume or mean pulmonary arterial pressure but did correlate to left ventricular end-diastolic volume (r = 0.62, P < 0.001). Leftward interventricular septum curvature was correlated to left ventricular filling rate (r = 0.64, P < 0.001) and left ventricular end-diastolic volume (r = 0.65, P < 0.001). In contrast, left atrial filling was normal and not correlated to left ventricular end-diastolic volume. In PAH patients, ventricular interaction mediated by the interventricular septum impairs left ventricular filling, contributing to decreased stroke volume.

Correction of phase offset errors in main pulmonary artery flow quantification.

PURPOSE: To investigate whether an existing method for correction of phase offset errors in phase-contrast velocity quantification is applicable for assessment of main pulmonary artery flow with an MR scanner equipped with a high-power gradient system. MATERIALS AND METHODS: The correction method consists of fitting a surface through the time average of stationary pixels of velocity-encoded phase images, and subtracting this surface from the velocity images. Pixels are regarded as stationary if their time standard deviation falls into the lowest percentile. Flow was measured in the main pulmonary artery of 15 subjects. Each measurement was repeated on a stationary phantom. The phase offset error in the phantom was used as a reference. Correction was applied with varying polynomial surface orders (0-5) and stationarity percentiles (5-50%). The optimal surface order and stationarity percentile were determined by comparing the fitted surface with the phantom. RESULTS: Using a first-order surface and a (noncritical) 25% percentile, the correction method significantly reduced the phase offset error from 1.1 to 0.35 cm/second (RMS), which is equivalent to a reduction from 11% to 3.3% of mean volume flow. Phase error correction strongly affected stroke volume (range -11 to 26%). CONCLUSION: The method significantly reduces phase offset errors in pulmonary artery flow.