Response to “Right Ventricular Dysfunction is Associated With Increased Mortality in Patients Requiring VV ECMO: Issues With the Method” (2022)

To the Editor We thank Lashin and Shah for their letter1 in response to our article.2 Cardiac magnetic resonance (CMR) imaging is widely accepted as the standard imaging method to evaluate right ventricular (RV) size and function.3 However, this was not a feasible test in this population for multiple reasons: the presence of the extracorporeal membrane oxygenation (ECMO) circuit containing metallic material; critical illness limiting the ability to transfer patients to the CMR scanner and perform breath holds; and SARS-CoV-2 exposure risk to staff. In the absence of CMR examinations, we chose the echocardiographic RV fractional area change (RVFAC) to evaluate RV size and function. It has been demonstrated to have a good correlation with CMR measures of RV size and function in multiple different populations.4–6 The RVFAC also has a stronger correlation with CMR-derived RV function than tricuspid annular plane systolic excursion (TAPSE), especially in critically ill patients with COVID-19 pulmonary disease.5–8 Moreover, our institutional practice is to focus on RVFAC rather than the RV tricuspid lateral annular systolic velocity wave (S′) or TAPSE. This is because RV S’ and TAPSE only reflect the longitudinal function of the basal portion of the RV neglecting contributions of the free wall, apical, and outflow tract components of RV ejection which may be disproportionally affected in conditions with elevated RV afterload, such as our population.9 In addition, they are dependent on the ultrasound angle and further influenced by passive translational and tethering forces.5 Lashin and Shah suggest that multivariate regression would be better to evaluate the association between RVFAC and mortality in our study. Multivariable (in this case, logistic) regression is ill-suited for this study due to the relatively small number of patients. The use of even a small number of variables in any multivariable regression model with this population risks overfitting the model. Knowing this, we used descriptive statistics and acknowledged that our study was limited by its sample size. We were also clear that our study was hypothesis-generating and that the observation of severely reduced RV function (as determined by the surrogate RVFAC) in patients with poor clinical outcomes despite veno-venous extracorporeal membrane oxygenation (VV-ECMO) warrants further studies. In response to Lashin and Shah’s concern regarding the comparability of RVFAC derived from transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE), we re-ran the analyses with the exclusion of the single patient for whom TEE-derived RVFAC was used. We found that the median RVFAC in patients that survived was 30.0% versus 11.3% in those that failed to decannulate from VV-ECMO (p = 0.0039). This demonstrates that our results are essentially unchanged when limiting the analysis to those with TTE-based RVFAC assessment. We also calculated the intra- and inter-observer variability in RVFAC in our study. The mean intra-observer difference for RVFAC was 1.6% (95% CI: −5.4% to 6.6%) and the mean inter-observer difference was 2.4% (95% CI: −10.1% to 14.9%). In summary, despite the limitations we describe, our data in VV-ECMO patients are directly in line with the existing published data suggesting that severe RV dysfunction portends a poor prognosis in other populations with SARS-CoV-2/COVID-19 infection.