Right Ventricle Dysfunction in Patients Undergoing Lung Transplant

This study is a prospective observational cohort analysis of echocardiographic studies and medical records of consecutive patients who underwent LUTX at our Institution from January 2021 to March 2023. All patients enlisted for LUTX during the study period were considered for inclusion. Exclusion criteria were: 1) single LUTX; 2) re-transplantation; 3) patients bridged to LUTX with veno-venous ECLS; 4) missing medical records. At our Institution, at enlistment for LUTX, patients undergo a comprehensive cardiac evaluation, comprising: 1) invasive right heart catheterization; 2) multi-gated radionuclide ventriculography; 3) trans-thoracic echocardiography performed by a specialized cardiologist. For further details on the management of LUTX at our Institution, see Online Supplement, Additional Methods.

To conduct this study, following enlistment, the research team contacted the patients, and a specialized sonographer (SS) and a specialized cardiologist (PM) blinded to the results of the enlistment echocardiography, carried out a further echocardiographic examination for the measurement of RV strain. Specifically, a GE Vivid IQ machine (GE Healthcare, Milwaukee, WI) was used. Images were acquired during breath holds with stable electrocardiographic recordings and digitally stored for subsequent offline analysis using EchoPAC Clinical Workstation Software (GE Healthcare, Milwaukee, WI). RV global longitudinal strain (RVGLS) and RV free wall strain (RVFWS) were calculated ex-post using conventional the two-dimensional echocardiographic apical 4-chamber (17,18) or - when inaccessible - subcostal view.

Thus, according to the most recent data available, patients were classified as having and abnormal (>-16.9%), borderline (between -16.9% and -19.2%), and normal (< -19.2%) RVFWLS.

We obtained the following measurement following international guidelines: right atrium (RA) area, RV end-diastolic area (RV EDA), RV free wall thickness, fractional area change (FAC), M-mode measured tricuspid annular plane excursion (TAPSE), pulsed-wave tissue Doppler imaging (TDI) tricuspid peak annulus systolic velocity (S'), and pulmonary artery systolic pressure (PAPs).

The following data at the time of enlisting for LUTX were prospectively collected: demographics, weight, height, the indication to LUTX (further aggregated in pulmonary fibrosis vs. not pulmonary fibrosis), comorbidities, lung allocation score (LAS), oxygen requirement at rest, spirometry, arterial blood gas analyses, diffusing capacity of carbon monoxide (DLCO), six-minute walking test (6MWT), pulmonary arterial pressures and cardiac output (by invasive cardiac catheterization); pulmonary scintigraphy; right ventricle ejection fraction (RVEF) measured by multi-gated radionuclide ventriculography.

Statistical analysis Data were reported as the median [first-third quartile] and number of events (percentage of the subgroup) for continuous and categorical variables, respectively. Patients without an available echocardiographic window for RV evaluation were not considered for the echocardiographic analysis. The Z-test was utilized to compare the patients' population with standard normality values(12,21,22). The correlation between continuous variables was tested with the R2 linear regression. Sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPV) and associated confidence intervals (CI) of RVFWS (vs. TAPSE, FAC, S', multi-gated radionuclide ventriculography) were computed. Comparison between patients' cohorts (i.e., normal RVLS vs. compromised RVLS) was performed with Chi2 or Fisher Exact Test, and logistic regressions, as appropriate. The odds ratios (OR) and associated 95% likelihood ratio-based confidence intervals were calculated. Statistical significance was accepted at P < 0.05. The JMP® pro 16.0 (SAS, Cary, NC) was utilized.

Inclusion criteria

• Enlistment for bilateral LUTX
• Age > 18 years
• Signed informed consent

Exclusion criteria

• Age < 18 years old
• Urgency enlistment
• Already undergone LUTX
• Extracorporeal membrane oxygenation (ECMO) bridging to LUTX
• Poor acoustic windows which limit the adequate acquisition of the echocardiographic pictures
• Congenital heart disease
• Previous cardiac surgery