Gender Differences and Outcomes of Hypoattenuated Leaflet Thickening (HALT) Following Transcatheter Aortic Valve Replacement: A Meta-analysis of Randomized and Cohort Studies.

Subclinical leaflet thrombosis is characterized by hypoattenuated leaflet thickening (HALT) after transcatheter aortic valve replacement (TAVR) on computed tomography. However, given the low incidence of HALT after TAVR, the clinical significance of HALT is still being investigated. We sought to generate a more reliable estimate of the risk factors and adverse outcomes associated with HALT after TAVR by pooling data from randomized trials and cohort studies. PubMed/Medline database was systematically searched from inception until November 24, 2021, using the following terms: ("hypoattenuated leaflet thickening" and "transcatheter aortic valve replacement") and ("Subclinical leaflet thrombosis" and "transcatheter aortic valve replacement"). A random effects model meta-analysis was conducted using Mantel-Haenszel odds ratios (ORs) and the associated 95% confidence intervals (CIs), mean difference and the associated 95%. Ten studies with a total of 1462 patients were included, with follow-up ranging between 4 months and 3 years. HALT occurred in 14.4% of the patients undergoing TAVR. HALT was not associated with increased risk of stroke/TIA (OR 1.38; 95% CI [0.61-3.11]; I2=0%) or increased risk of all-cause mortality (OR 0.67; 95% CI [0.25-1.80]; I2=0). HALT was associated with a greater post-procedural mean aortic valve gradient (mean difference 2.31 mmHg; 95% CI [0.27, 4.35]; I2=71%). Interestingly, there was a trend of higher risk of HALT in men (OR 1.37; 95% CI [0.82-2.30]; I2=44%) while there was a trend towards lower risk of HALT in the presence of CKD (OR 0.76; 95% CI [0.49-1.19]; I2=0%); these trends did not reach statistical significance. This meta-analysis shows that the occurrence of HALT following TAVR is associated with a greater post-procedural mean aortic valve gradient but no excess risk of death or cerebrovascular events. The clinical significance of this higher post-procedural mean aortic valve gradient is uncertain and requires further investigations.