The use of multiphase computed tomography (CT) assessment, particularly during the early systolic phase, of the neo-left ventricular outflow tract (LVOT) is a better predictor of clinically relevant obstruction in transcatheter mitral valve replacement (TMVR) than end systole measurements. The authors of the analysis of a cohort of patients in the Intrepid Global Pilot Study, published in JACC: Cardiovascular Interventions, say that the approach has the potential to significantly increase patient eligibility for treatment, with more than half of those who had previously failed screening being judged suitable for the therapy.
Christopher U Meduri (Piedmont Heart Institute, Atlanta, USA) et al write: “These advances have the potential to reduce the screen failure rate in TMVR clinical trials and improve the accessibility of this therapy to additional patient populations previously screen-failed from TMVR trials. Further, these findings are likely not device-specific, and may therefore be generalised to additional TMVR devices.”
Patients often-fail screening for transcatheter mitral valve replacement (TMVR) trials because of the perceived risk of left ventricular outflow tract obstruction (LVOTO). In the ongoing Intrepid Global Pilot Study, assumed risk of LVOTO was based on CT estimates of the neo-LVOT area computed at end-systole.
However, the investigators hypothesised that this may overestimate actual risk. “This end-systolic assessment may represent a worst-case approximation of the neo-LVOT area and risk for LVOTO. Early experience in this trial has demonstrated an approximately 40% screen failure rate among patients within the treatable range for annulus size using this method. Furthermore, there has not been a clinically significant LVOTO in those patients treated. To address this, we propose a physiologic assessment of LVOTO, which accounts for the changes in flow throughout systole, as well as the dynamic nature of the neo-LVOT. Specifically, we hypothesise that an assessment of both multi- and early-systolic phase would better predict clinically relevant LVOTO, and that early systolic phase may be the most accurate predictor, as blood flow out of the ventricle in patients with MR [mitral regurgitation] varies with time with substantial flow in early systole. If proven, these advances may potentially reduce the screen failure rate for high LVOTO risk.”
Of 166 patients screened (screen-failed and screen-accepted) in the Intrepid Pilot Study, 50 treated patients from the Early Feasibility Study were considered for the present analysis. Meduri and colleagues performed both a retrospective analysis and a prospective evaluation. The retrospective cohort consisted of patients who failed screening due to concerns about potential LVOTO (n=33), and treated patients (n=29) who were analysed with available contrast-enhanced dynamic CT. A subset of these treated patients (n=20) were used for paired analyses of CT and echocardiographic assessment at baseline and 30-days post-procedure. The retrospective analyses included estimates of predicted neo-LVOT areas at end-systole and assessment at multi- and early-systolic phases.
The prospective validation cohort consisted of nine patients enrolled in the Intrepid Global Pilot Study between June 2017 and June 2018 using multiphase (six) or early systolic (three) criteria. Based on end-systolic CT screening, these patients would have been screen-failed, due to predicted LVOTO risk. Baseline and 30-day echocardiography data were reported.
The researchers found that, of the 166 patients screened for possible inclusion, 32 were screen-failed for non-anatomical reasons. Screen failure for assumed LVOTO risk occurred in 37/134 (27.6%) patients. Retrospective analysis indicated a potential enrolment increase of 11/33 (33.3%) using multiphase assessment and 18/33 (54.5%) patients with early systolic analysis. In the prospective cohort there were no clinical observations of LVOTO 30 days’ post procedure, despite assumed risk based on end-systolic estimates.
Meduri et al conclude: “Our findings demonstrate that one-third of previously screen-failed patients would now be eligible for enrolment based on multiphase alone. Using the early systolic method, an additional 21% of previously screen-failed patients would be eligible for enrolment. The proportion of eligible TMVR patients may increase by more than half, as evidenced by our series.”
They note the small sample size in the study, and that predicting LVOTO risk is a new technique, with “much to be learned from ongoing trials and case experience”. However, they add: “As the field advances, we predict further refinement around the ideal cutoff value that should be used.”
In an accompanying comment, also published in JACC: Cardiovascular interventions, Jonathon Leipsic and Philipp Blanke (St. Paul’s Hospital, University of British Columbia, Vancouver, Canada) agree that, although the sample size “seems like modest clinical evidence”, the findings should be considered within the context of the “nascent nature of the field of TMVR, where only a few hundred procedures have been performed to date”.
They advise: “These findings have potential significant implications given the slow enrolment of active randomised trials, at least in part due to a significant burden of screen failure. It is highly unlikely that these patient specific models will be ready for clinical integration any time soon. Until then, the field will need to continue to integrate new learnings, such as those provided by Meduri and colleagues, to help with safe but not overly conservative patient screening and selection for TMVR.”
Senior author Vinayat Bapat (New York Presbyterian Hospital Columbia University Medical Center, New York, USA) emphasised to Cardiovascular News: “The refined algorithm suggested by the study will definitely increase the number of patients recruited in TMVR studies. I also feel that ‘device specific’ LVOT cutoff value needs to be defined as each device interacts with LVOT differently.”