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.