Non-Invasive Determination of Cardiac Output in Pre-Capillary Pulmonary Hypertension

Abstract

Background: Cardiac output (CO) is a major diagnostic and prognostic factor in pre-capillary pulmonary hypertension (PH). Reference methods for CO determination, like thermodilution (TD), require invasive procedures and allow only steady-state measurements. The Modelflow (MF) method is an appealing technique for this purpose as it allows non-invasive and beat-by-beat determination of CO.

Methods: We aimed to compare CO values obtained simultaneously from non-invasive pulse wave analysis by MF (COMF) and by TD (COTD) to determine its precision and accuracy in pre-capillary PH. The study was performed on 50 patients with pulmonary arterial hypertension (PAH) or chronic thrombo-embolic PH (CTEPH). CO was determined at rest in all patients (n = 50) and during nitric oxide vasoreactivity test, fluid challenge or exercise (n = 48).

Results: Baseline COMF and COTD were 6.18 ± 1.95 and 5.46 ± 1.95 L·min-1, respectively. Accuracy and precision were 0.72 and 1.04 L·min-1, respectively. Limits of agreement (LoA) ranged from -1.32 to 2.76 L·min-1. Percentage error (PE) was ±35.7%. Overall sensitivity and specificity of COMF for directional change were 95.2% and 82.4%, (n = 48) and 93.3% and 100% for directional changes during exercise (n = 16), respectively. After application of a correction factor (1.17 ± 0.25), neither proportional nor fixed bias was found for subsequent CO determination (n = 48). Accuracy was -0.03 L·min-1 and precision 0.61 L·min-1. LoA ranged from -1.23 to 1.17 L·min-1 and PE was ±19.8%.

Conclusions: After correction against a reference method, MF is precise and accurate enough to determine absolute values and beat-by-beat relative changes of CO in pre-capillary PH.

Fig 1. Study profile.

PH: Pulmonary hypertension; LHD–PH: PH due to left heart disease; ILD–PH: PH due to interstitial lung disease; PAH: Pulmonary arterial hypertension; CTEPH: Chronic thromboembolic PH.

Fig 2. Comparison of baseline values of CO_MF and CO_TD.

Simultaneous determination of cardiac output by thermodilution (CO_TD) and Modelflow (CO_MF) in 50 patients with pre-capillary pulmonary hypertension. (A) The figure describes median (line), 25th to 75th percentile (box), 5th to 95th percentile (whiskers) and the dots represent outliers. The mean values for CO_TD and CO_MF were 5.46 ± 1.95 L·min^-1 and 6.18 ± 1.95 L·min^-1, respectively (p<0.05). (B) Difference between resting CO_MF and CO_TD values plotted against their mean. Broken line represents the mean (+ 0.72 L·min^-1) and the solid lines the 95% limits of agreement (-1.32 to + 2.76 L·min^-1).

Fig 3. Relationship between CO_MF and CO_TD.

COMF determined in 50 patients (98 values) under various conditions (rest, fluid challenge, NO testing and exercise). CO_MF values were plotted against the corresponding CO_TD values for CTEPH patients (A) PAH patients (B) and all 50 patients (C). (D) Difference between CO_MF and CO_TD values plotted against their mean. In (A), (B) and (C), the broken lines correspond to the lines of equality, solid lines are the mean regression lines and dotted lines delimit the confidence interval of the regression lines. In (D), broken line represents the mean (+ 1.05 L·min^-1) and the solid lines the 95% limits of agreement (-1.30 to + 3.40 l.min^-1).

Fig 4. Relationship between CO_MFcorr. and CO_TD.

COMFcorr. determined in 26 patients (48 values). (A) For each subject, CO_MFcorr. values were plotted against the corresponding CO_TD values. The broken line corresponds to the line of equality, solid line is the mean regression lines and dotted lines delimit the confidence interval of the regression lines. (B) Difference between CO_MFcorr. and CO_TD values plotted against their mean. Broken line represents the mean (-0.03 L·min^-1) and the solid lines the 95% limits of agreement (-1.23 L·min^-1 to +1.17 L·min^-1).

Fig 5. Relationship between CO_MFcorr. and CO_TD during exercise.

CO_MFcorr determined in 6 patients during exercise procedure. (A) For each subject, CO_MFcorr values were plotted against the corresponding CO_TD values. The broken line corresponds to the line of equality, solid line is the mean regression lines and dotted lines delimit the confidence interval of the regression lines. (B) Difference between CO_MFcorr and CO_TD values plotted against their mean. Broken line represents the mean (-0.15 L·min^-1) and the solid lines the 95% limits of agreement (-1.42 l.min^-1 to +1.12 L·min^-1). (C) For each subject and workload, the increase (Δ) in CO_MFcorr from rest was plotted against the same corresponding CO_TD increase (ΔCO_TD). The six different targets correspond to the six different patients. The broken line corresponds to the line of equality.