METHODS
STUDY POPULATION. Echocardiographic examinations of consecutive patients with clinically judged HF referred for RHC to the Karolinska University Hospital between 2014 to 2018 were retrospectively reviewed. All subjects were hemodynamically stable during assessment and medical therapy was suitably titrated. Patients in atrial fibrillation or with significant arrhythmias and/or poor echocardiographic image quality precluding accurate measurement were excluded. Thereafter, subjects with isolated pre-capillary alterations on right heart catheterization were excluded from the analysis. The study was approved by the local ethics committees (Karolinska: DNR 2008/1695-31) and all patients provided written informed consent.
ECHOCARDIOGRAPHIC EVALUATION. All patients underwent comprehensive echocardiography employing a Vivid E9 ultrasound system (GE Ultrasound, Horten, Norway) by a single experienced echocardiographer (AV) in keeping with current recommendations.14 2D gray-scale images were acquired at 50-80 frames/sec and Doppler tracings were recorded using a sweep speed of 100mm/sec. Three consecutive heart cycles were acquired in sinus rhythm. TR was measured with Continuous wave Doppler, considering the most optimal signal obtained from multiple echocardiographic windows. PR was obtained with Continuous wave Doppler from the parasternal short-axis view at the level of the semi-lunar valves. Right ventricular outflow tract (RVOT) flow was obtained by placing a 5-mm Pulsed Doppler signal in the right ventricular outflow tract just proximal to the pulmonic valve. All images were subsequently exported and analyzed offline (EchoPAC PC, version 11.0.0.0 GE Ultrasound, Waukesha, Wisconsin) by an experienced, credentialed echocardiographer blinded to catheterization data.
A summary of approaches employed to evaluate PAPM are illustrated in Figure 1. Broadly, PAPM was evaluated using 4 algorithms taking into consideration 3 different approaches employing TR- ,5 8 PR- ,7 and RVOT acceleration time (RVOTAT).6 Applying the approach postulated by Aduen et al., 5PAPM was estimated by adding TR mean pressure gradient to recommended estimates of right atrial pressure (RAP) obtained from inferior vena cava (IVC) size and collapsibility.14The second approach adopted from Chemla et al. incorporated estimated systolic pulmonary artery pressure (PAPS) obtained by adding the gradient corresponding with peak TR velocity (TRVmax) to IVC-estimated RAP to calculate PAPM using the relationship PAPM = 0.61 × PAPS + 2 mm Hg.8 In the third approach (Abbas and colleagues), PAPM was estimated by adding gradients obtained from peak PR velocity to corresponding IVC-estimated RAP.7 Finally, in the fourth approach proposed by Dabestani et al, RVOTAT was defined during systole as time in milliseconds from beginning of flow to peak velocity. PAPmean was then calculated as PAPmean = 90 − (0.62 x RVOTAT) when AT < 120msec and 79 – (0.45 x RVOTAT) when AT ≥ 120msec.6
INVASIVE EVALUATION. Echocardiographic examinations were followed by RHC within a 1-hour period. Pharmacological status was unaltered between echocardiography and catheterization. RHC was performed by experienced operators blinded to echocardiography examinations using a 6F Swan Ganz catheter employing jugular or femoral vein access. After suitable calibration with the zero-level set at the mid-thoracic line, pressure measurements were taken from the right atrium (RA), right ventricle (RV) and pulmonary artery (PA) during end-expiration. Five to 10 cardiac cycles were acquired and all pressure tracings were stored and analyzed offline using a standard hemodynamic software package (WITT Series III, Witt Biomedical Corp., Melbourne, FL).
STATISTICAL ANALYSIS. Normality was tested using the Shapiro-Wilk test and visually reaffirmed using QQ plots. Continuous variables were expressed as mean ± SD for parametric variables or median (interquartile range) for non-parametric variables and categorical variables were expressed as numbers and percentage. Correlations between Doppler PAPM approaches and corresponding invasive measurements were performed using the Pearson’s 2-tailed test (correlation between 2 continuous variables). Accuracy was defined as the difference of the mean bias and precision as the spread of data points between echocardiographic and invasive measurements on Bland-Altman analysis. Receiver operating characteristics (ROC) curve was employed to illustrate diagnostic potential of both TRVmax and echocardiographic algorithms. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were measured. IBM SPSS statistics version 23.0 was employed for analysis.