Mahajan, Anushka Vishwas

Abstract Aims Randomized trials comparing percutaneous left atrial appendage occlusion (LAAO) with oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation have yielded conflicting results across device generations and anticoagulant eras. This Bayesian meta-analysis of randomized trials aimed to compare LAAO vs. OAC for stroke or systemic embolism (SSE) and non-procedural clinically relevant bleeding (CRB). Methods and results We conducted a systematic search across five databases (PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL) to identify randomized trials of LAAO vs. OAC. Primary outcomes of stroke or systemic embolism, non-procedural CRB and clinical benefit composite were estimated using a Bayesian hierarchical random effects model and findings confirmed across robust sensitivity and subgroup analyses. Posterior probabilities for superiority, non-inferiority and equivalence were estimated using clinically meaningful margins. Six randomized trials including 7004 participants in the intention-to-treat groups, were analysed. LAAO was not associated with lower SSE vs. OAC (pooled RR, 1.11; 95% CrI, 0.80–1.49), with a 74.6% posterior probability of favouring OAC. The posterior probability of crossing non-inferiority was P(HR < 1.4) of 89%. In contrast, LAAO reduced non-procedural CRB (pooled RR, 0.59; 95% CrI, 0.45–0.78). The net clinical benefit composite, pooling contemporary trials, demonstrated a pooled RR of 0.90 (95% CrI 0.51–1.50), with P(RR < 1) of 76%, with substantial heterogeneity for this outcome. Conclusion This Bayesian meta-analysis found no clear evidence supporting clinically meaningful non-inferiority of LAAO over OAC for stroke prevention. Despite reduced non-procedural bleeding, LAAO did not demonstrate a similar reduction in major bleeding.

Background: In patients with paradoxical low-gradient severe aortic stenosis (AS) based on aortic valve area (AVA) at rest (<1cm2) and normal left ventricular ejection fraction (LVEF >50%), the role of dobutamine stress echocardiography (DSE) is unclear. While current guidelines recommend assessing aortic valve calcium score in this context, DSE may still offer clinical value. Methods: We conducted a retrospective study on patients with paradoxical low gradient AS (LVEF >50% AVA <1cm 2 , MG < 40 mmHg) at rest who underwent DSE after Institutional Review Board approval. Data was extracted using an internal database. Patients > 18 yrs old with LVEF >50%, mean gradient (MG) < 40 mmHg, and valve area < 1 cm 2 at rest were included. Kruskal-Wallis test was used to identify which resting variables were associated with severe AS (MG >40 mm Hg and Valve area <1 cm 2 ) with DSE. Results: A total of 42 patients were included in the study and variables were reported as means (±SD). The mean age of patients was 78 years (±10) and 60% were female. The mean resting LVEF was 60% (±5%), MG at rest was 28 mmHg (±7) while it was 40 mmHg (±14) with DSE, and mean aortic valve area at rest was 0.9 cm 2 (±0.09) while it was 1.1 cm 2 (±0.23) with DSE. Of the 42 patients, 11 (26%) were found to have severe AS during DSE, defined by a MG >40 mmHg and AVA <1.0 cm 2 . Baseline AVA and MG at rest were significantly associated with severe AS on DSE (p=0.008 and p=0.024, respectively), while age, stroke volume index, and baseline LVEF were not. Univariate regression analysis showed that the area under the curve (AUC) for predicting severe AS was 0.73 for resting MG and 0.77 for resting AVA. A resting AVA cutoff of 0.78 cm 2 provided optimal sensitivity (0.63) and specificity (0.90). For resting MG, a cutoff of 29 mmHg gave a sensitivity of 0.91 and specificity of 0.68 for identifying patients with severe AS. Conclusion: Our study indicated that DSE remains useful in identifying severe AS in substantial number of patients (26%) who exhibit paradoxical low gradient severe AS. Additionally, AVA at rest and baseline mean gradient were statistically the reliable parameters to determine those who may benefit significantly from undergoing DSE. This is one of the first studies to our knowledge in the literature suggesting that DSE may still be useful in identifying severe AS patients despite “paradoxical low gradient severe AS” at rest. Further research is warranted to validate our findings.