Methods
The echo core Lab of the Institute of Clinical Physiology-CNR in Pisa
(LG) coordinated the quality control procedure of all investigators at
different centres participating in the RIGHT-NET study. Each center
designated one operator that performed or reported at least 100 stress
echocardiography studies per year. All readers were certified by
national and/ or international societies. The quality control process
was designed to be simple, repeatable, and sustainable. The Echo Core
Lab issued a User Manual with a detailed description on how to measure
each parameter, according to the most recent American and European
Recommendations and Guidelines.8-11 The User Manual
was sent to all Participating Centers including the reference for
transthoracic echocardiography assessment. All participating centers
followed the recommended standard operational procedures in terms of
data data storage (data format, transfer procedure), and data processing
(software used and measurement procedures). All operators performing and
reading echocardiographic exams adhered to the quality control protocol.
The Echo Core Lab sent ten complete echocardiographic examinations in
DICOM format through a safe file sharing platform (Fig. 1) . All
participating investigators were invited by email to join the platform,
which was protected by user-specific passwords. The platform includes
also detailed instructions on how to start the training and allows
downloading and uploading of external files. All images and videos were
completely anonymized to protect patients’ privacy, according to the new
EU directive of protection of personal data (GDPR).6
Reading sessions
We randomly selected 10 cases including healthy subjects and at least
one group of patients with overt and/or at risk of pulmonary
hypertension (PH), according to clinical classification of PH(Table 1) .12 Data were collected on patients
undergoing EDE on a semi-recumbent cycle ergometer with an incremental
workload of 25 Watts every 2 minutes up to the symptom-limited maximal
tolerated workload including resting, 50 Watts, peak stress and recovery
acquisition, as previously described.6 All operators
directly measured the requested parameters by uploading the same ten
cases from the web platform to their echocardiography machine. The DICOM
format enabled to perform assessment of variables in the respective
centres. All operators were then asked to enter their measurements in a
dedicated excel file, which was then sent to the Coordinating Center for
analysis. Table 2 provides the list of the left and the right
heart parameters measured by all operators. The gold standard value for
each measurement was established by the values measured by the Echo Core
Lab.
Statistical analysis
Statistical analysis was performed using standard software (MedCalc
version 14.8.1, MedCalc Software Ltd, Belgium; SPSS version 20.0, SPSS,
Inc., Chicago, IL). Continuous variables were described by mean values ±
standard deviation (SD). Accuracy (in %) for each observer was
estimated by comparison with the reference standard (core lab reading).
Intra-class correlation coefficient (ICC) was calculated along with the
95% confidence interval, in order to quantify the reliability of
measurement process. An ICC of >0.8 indicated excellent
agreement with the core lab. Inter-observer variability among 19
observers were examined for resting and peak exercise TRV, RVOT Act,
TAPSE, S’, right ventricular fractional area change (RV FAC), LVOT
velocity time integral (VTI), mitral early inflow pulsed wave Doppler
velocity (E), early diastolic mitral annular lateral and septal velocity
by TDI (e’), left ventricular ejection fraction (LVEF). Data are
presented as mean of the absolute and relative differences (in %)
between measurements.
Intra-observer agreement was tested in 2 observers who volunteered to
repeat the measurement session on 2 separate days and ICC was
calculated.