Pulmonary vascular input impedance is a combined measure of pulmonary vascular resistance and stiffness and predicts clinical outcomes better than pulmonary vascular resistance alone in pediatric patients with pulmonary hypertension

Department of Pediatric Cardiology, University of Colorado Health Sciences Center, Denver, CO, USA.
American heart journal (Impact Factor: 4.56). 02/2008; 155(1):166-74. DOI: 10.1016/j.ahj.2007.08.014
Source: PubMed

ABSTRACT Pulmonary vascular resistance (PVR) is the current standard for evaluating reactivity in children with pulmonary arterial hypertension (PAH). However, PVR measures only the mean component of right ventricular afterload and neglects pulsatile effects. We recently developed and validated a method to measure pulmonary vascular input impedance, which revealed excellent correlation between the zero harmonic impedance value and PVR and suggested a correlation between higher-harmonic impedance values and pulmonary vascular stiffness. Here we show that input impedance can be measured routinely and easily in the catheterization laboratory, that impedance provides PVR and pulmonary vascular stiffness from a single measurement, and that impedance is a better predictor of disease outcomes compared with PVR.
Pressure and velocity waveforms within the main pulmonary artery were measured during right heart catheterization of patients with normal pulmonary artery hemodynamics (n = 14) and those with PAH undergoing reactivity evaluation (49 subjects, 95 conditions). A correction factor needed to transform velocity into flow was obtained by calibrating against cardiac output. Input impedance was obtained off-line by dividing Fourier-transformed pressure and flow waveforms.
Exceptional correlation was found between the indexed zero harmonic of impedance and indexed PVR (y = 1.095x + 1.381, R2 = 0.9620). In addition, the modulus sum of the first 2 harmonics of impedance was found to best correlate with indexed pulse pressure over stroke volume (y = 13.39x - 0.8058, R2 = 0.7962). Among a subset of patients with PAH (n = 25), cumulative logistic regression between outcomes to total indexed impedance was better (R(L)2 = 0.4012) than between outcomes and indexed PVR (R(L)2 = 0.3131).
Input impedance can be consistently and easily obtained from pulse-wave Doppler and a single catheter pressure measurement, provides comprehensive characterization of the main components of RV afterload, and better predicts patient outcomes compared with PVR alone.

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Available from: Kendall S Hunter, Jul 30, 2015
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    • "Previous findings in adult PAH patients indicated that PAC and PSV may be valuable predictors for prognosis in adult PAH [18] [19] [20] [21]. In paediatric PAH, PAC has previously been shown to be associated with pulmonary vascular disease severity, however its prognostic value for mortality is not clear [22] [23] [24]. The purpose of this study was to determine the prognostic value of PSV and PAC in children with idiopathic/hereditary PAH (IPAH/HPAH) and PAH associated with congenital heart disease (PAH-CHD). "
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    ABSTRACT: BACKGROUND: There is a need for reliable prognostic parameters in pulmonary arterial hypertension (PAH), especially in children. Pulsatile components of the right ventricular afterload, represented by pulmonary arterial compliance (PACi) and pulmonary stroke volume (PSVi), may provide important additional prognostic information to conventional static haemodynamic parameters. The aim of this study was to determine the prognostic value of PACi and PSVi in paediatric PAH. METHODS: Right heart catheterization data of 52 consecutive paediatric idiopathic/hereditary PAH and PAH associated with congenital heart disease patients with full haemodynamic evaluation seen at the Dutch national referral centre for paediatric pulmonary hypertension between 1993 and 2010 were reviewed. A control group was composed of patients with normal pulmonary vascular resistance. PSVi and PACi were calculated and tested for predictive value for transplant-free survival. RESULTS: PAH patients had significantly lower PSVi and PACi compared to control patients. PSVi and PACi were lower in patients with higher WHO-functional class compared to those with lower functional classes. Higher PSVi, PACi and mSAP and lower mPAP/mSAP and heart rate were associated with improved survival, independent from WHO-functional class and PAH-targeted therapy. In multivariate analyses PSVi, heart rate and mSAP emerged as the strongest haemodynamic predictors of survival. The effect of vasodilator challenge on the haemodynamic variables did not provide additional prognostic information. CONCLUSIONS: The parameters of both the pulsatile and static pulmonary circulations are strong independent predictors for transplant-free survival, and therefore can be of complementary value in assessing disease severity, predicting survival and guiding treatment in paediatric PAH.
    International journal of cardiology 01/2013; 168(2):1370-7. DOI:10.1016/j.ijcard.2012.12.080 · 6.18 Impact Factor
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    • "For a recent review, see (Wang and Chesler 2011). Also, the fact that increased extralobar PA stiffness is currently the best predictor of mortality in all types of PAH (Mahapatra, Nishimura et al. 2006; Gan, Lankhaar et al. 2007; Hemnes and Champion 2008; Hunter, Lee et al. 2008) strongly suggests that PA stiffening strongly contributes to right ventricular failure. We have previously shown that excessive PA collagen accumulation is associated with high-strain PA stiffening (Ooi, Wang et al. 2010). "
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    ABSTRACT: Pulmonary arterial hypertension (PAH) is caused by narrowing and stiffening of the pulmonary arteries that increase pulmonary vascular impedance (PVZ). In particular, small arteries narrow and large arteries stiffen. Large pulmonary artery (PA) stiffness is the best current predictor of mortality from PAH. We have previously shown that collagen accumulation leads to extralobar PA stiffening at high strain (Ooi et al. 2010). We hypothesized that collagen accumulation would increase PVZ, including total pulmonary vascular resistance (Z(0)), characteristic impedance (Z(C)), pulse wave velocity (PWV) and index of global wave reflections (P(b)/P(f)), which contribute to increased right ventricular afterload. We tested this hypothesis by exposing mice unable to degrade type I collagen (Col1a1(R/R)) to 21 days of hypoxia (hypoxia), some of which were allowed to recover for 42 days (recovery). Littermate wild-type mice (Col1a1(+/+)) were used as controls. In response to hypoxia, mean PA pressure (mPAP) increased in both mouse genotypes with no changes in cardiac output (CO) or PA inner diameter (ID); as a consequence, Z(0) (mPAP/CO) increased by ~100% in both genotypes (p<0.05). Contrary to our expectations, Z(C), PWV and P(b)/P(f) did not change. However, with recovery, Z(C) and PWV decreased in the Col1a1(+/+) mice and remained unchanged in the Col1a1(R/R) mice. Z(0) decreased with recovery in both genotypes. Microcomputed tomography measurements of large PAs did not show evidence of stiffness changes as a function of hypoxia exposure or genotype. We conclude that hypoxia-induced PA collagen accumulation does not affect the pulsatile components of pulmonary hemodynamics but that excessive collagen accumulation does prevent normal hemodynamic recovery, which may have important consequences for right ventricular function.
    Journal of Biomechanics 12/2011; 45(5):799-804. DOI:10.1016/j.jbiomech.2011.11.020 · 2.50 Impact Factor
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    • "Note that the above calculation assumes that the instantaneous cross-section area is constant over time and the spatial profile of the velocity is nearly constant across the vessel (Womersley 1955), which together have been shown previously to be acceptable approximations (Weinberg et al 2004). The recorded pressure and calculated flow time histories were then separated and collected into individual cardiac cycle-based electrocardiographic (ECG) gating; more detail may be found elsewhere (Hunter et al 2008). "
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    ABSTRACT: Pulmonary vascular input impedance better characterizes right ventricular (RV) afterload and disease outcomes in pulmonary hypertension compared to the standard clinical diagnostic, pulmonary vascular resistance (PVR). Early efforts to measure impedance were not routine, involving open-chest measurement. Recently, the use of pulsed-wave (PW) Doppler-measured velocity to non-invasively estimate instantaneous flow has made impedance measurement more practical. One critical concern remains with clinical use: the measurement uncertainty, especially since previous studies only incorporated random error. This study utilized data from a large pediatric patient population to comprehensively examine the systematic and random error contributions to the total impedance uncertainty and determined the least error prone methodology to compute impedance from among four different methods. We found that the systematic error contributes greatly to the total uncertainty and that one of the four methods had significantly smaller propagated uncertainty; however, even when this best method is used, the uncertainty can be large for input impedance at high harmonics and for the characteristic impedance modulus. Finally, we found that uncertainty in impedance between normotensive and hypertensive patient groups displays no significant difference. It is concluded that clinical impedance measurement would be most improved by advancements in instrumentation, and the best computation method is proposed for future clinical use of the input impedance.
    Physiological Measurement 06/2010; 31(6):729-48. DOI:10.1088/0967-3334/31/6/001 · 1.62 Impact Factor
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