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

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Figure 1

Quartiles of A) age, B) mean pulmonary artery pressure (MPAP), C) pulmonary vascular resistance (PVR), D) 0^th harmonic of impedance (Z₀), and E) higher-harmonic sum of impedance (Z₁+Z₂).

Figure 2

Graphical user interface for semi-automatic impedance computation. At center top is transient PW-Doppler data with an overlain computed envelope trace; at center bottom, the corresponding AUX1 (pressure) and ECG signals in yellow and blue, respectively.

Figure 3

Typical impedance curves from A) Group I and B) Group II patients. Diagnoses: Patient 1, ASD, secundum, device closure; Patient 2, PDA coil embolization, minimal residual shunting; Patients 3-4, PDA coil embolization, no residual shunting; Patient 10, secondary PAH, ASD, secundum + A-P Collateral arteries; Patient 14, secondary PAH, Down’s Syndrome, ASD device closure; Patient 31, primary PAH; Patient 41, secondary PAH, ASD, secundum.

Figure 3

Typical impedance curves from A) Group I and B) Group II patients. Diagnoses: Patient 1, ASD, secundum, device closure; Patient 2, PDA coil embolization, minimal residual shunting; Patients 3-4, PDA coil embolization, no residual shunting; Patient 10, secondary PAH, ASD, secundum + A-P Collateral arteries; Patient 14, secondary PAH, Down’s Syndrome, ASD device closure; Patient 31, primary PAH; Patient 41, secondary PAH, ASD, secundum.

Figure 4

Indexed Z₀ –vs– clinically measured indexed pulmonary vascular resistance (PVRI) for all subjects (63 patients; 109 reactivity conditions).

Figure 5

Z₁+Z₂ –vs– clinically measured value of A) PVSI (indexed pulse pressure over stroke volume) B) PVRI, and C) main pulmonary artery pressure, for all subjects (63 patients; 109 reactivity conditions).

Figure 5

Z₁+Z₂ –vs– clinically measured value of A) PVSI (indexed pulse pressure over stroke volume) B) PVRI, and C) main pulmonary artery pressure, for all subjects (63 patients; 109 reactivity conditions).

Figure 5

Z₁+Z₂ –vs– clinically measured value of A) PVSI (indexed pulse pressure over stroke volume) B) PVRI, and C) main pulmonary artery pressure, for all subjects (63 patients; 109 reactivity conditions).

Figure 6

Cumulative logistic regression of outcomes –vs– Z sum (black) and PVR (red) (n=25).