Zou, Tian

ABSTRACT Introduction Cardiogenic shock (CS) carries high morbidity and mortality. However, evidence for mechanical circulatory support (MCS) in non‐ischemic CS remains limited, as prior trials have focused on infarct‐related shock. Methods We performed a retrospective cross‐sectional study using the Nationwide Inpatient Sample (2017–2019), identifying hospitalizations with a principal diagnosis of CS and excluding acute myocardial infarction. Patients were categorized into mutually exclusive groups: no MCS, intra‐aortic balloon pump (IABP) only, Impella only, or extracorporeal membrane oxygenation (ECMO) only. Primary outcomes were in‐hospital mortality, length of stay (LOS), and total hospital cost. Survey‐weighted multivariable models adjusted for demographics, hospital characteristics, and comorbidity burden using Elixhauser and Charlson indices. Results Among 104 045 hospitalizations, 6040 received MCS. IABP was most common, followed by Impella and ECMO. Among patients receiving a single MCS strategy, overall in‐hospital mortality was 29.5%., with lower mortality in the IABP group (19.9%) compared with Impella (37.4%) and ECMO (44.3%). After adjustment, IABP was associated with lower observed in‐hospital mortality versus no MCS (aOR 0.58, 95% CI 0.53–0.64; p < 0.01), whereas Impella and ECMO showed increased aOR. IABP and ECMO were associated with longer LOS, while Impella was not. All MCS strategies were associated with higher costs, with ECMO showing the greatest increase (cost ratio 3.30, 95% CI 3.12–3.50). Conclusion In non‐ischemic CS, MCS strategies demonstrate distinct profiles of mortality and resource utilization. IABP was associated with lower observed in‐hospital mortality, whereas all MCS were linked to higher costs, highlighting heterogeneity in outcomes and the need for further research.

ABSTRACT Background Optimal management of direct oral anticoagulants (DOAC) prior to implantation of cardiac implantable electronic devices (CIED) remains controversial. Objective To determine whether a strategy of minimal interruption of DOAC before cardiac CIED implantation is associated with improved clinical outcomes compared to uninterrupted DOAC use. Methods The electronic clinical records of 310 patients who were on DOAC and underwent CIED implantation were evaluated. The patients were separated into 2 groups: patients in Group 1 had minimal DOAC interruption (DOAC held < 24 h before procedure), while patients in Group 2 continued DOAC before procedure. Resumption of DOAC in both groups was on the same day of the procedure or the next morning at the operator's discretion. Clinically significant pocket hematoma and thromboembolic events were compared. Results Among the 310 patients, 71 (22.9%) of them had DOAC held < 24 h before procedure, while DOAC was continued without interruption in 239 (77.1%) in the periprocedural period. Clinically significant pocket hematomas were found in 1 patient (1.4%) in the DOAC interrupted group and 24 (10.0%) in the DOAC continuous group ( p = 0.046). Low thromboembolic events were observed in both groups: 0 in the minimally interrupted group and 1 (0.4%) in the un‐interrupted group ( p > 0.05). Conclusion The bleeding risk in our cohort of patients who underwent CIED implantation with the uninterrupted DOAC approach is higher than previously reported in the literature. A minimally interrupted approach appears to mitigate this risk without significantly increasing the risk of thromboembolism.

Background: Cardiac myosin-binding protein C (cMyBP-C, encoded by MYBPC3 ) and Sorbin and SH3 domain-containing protein 2 (Sorbs2, encoded by SORBS2 ) are critical sarcomeric components that maintain cardiac structure and function. MYBPC3 and SORBS2 are linked to hypertrophic and dilated cardiomyopathies. But the relationship between Sorbs2 and cMyBP-C regulation, and their roles in the pathogenesis of atrial fibrotic cardiomyopathy (AFCM), remains unclear. Hypothesis: Sorbs2 acts as a cytoskeletal and RNA-binding protein that regulates cMyBP-C expression in atrial myocardium. Methods: We created the cardiac-specific Sorbs2 knockout ( c-Sorbs2 KO mice. We used next-generation RNA sequencing, molecular biology techniques, and in silico analysis to study how Sorbs2 regulates cMyBP-C expression in the atria of c-Sorbs2 KO mice. Results: Compared to age-matched wild-type (WT) mice at 8-9 months of age, the c-Sorbs2 KO male exhibited significant left atrial (LA) enlargement (diameter: 2.41±0.11 mm vs 1.82 ± 0.05 mm in WT; n = 8; p < 0.001) and severe atrial fibrosis (fibrotic area: 12.29±1.73 vs 2.83 ± 0.41% in WT; p < 0.001), accompanied by marked reductions in both mRNA and protein levels of cMyBP-C in LA. In vitro knock-down of Sorbs2 by 60% via shRNA led to an 86.3% decrease in cMyBP-C protein levels, while a 3-fold Sorbs2 overexpression via adenoviral transduction resulted in a 1.4-fold increase in cMyBP-C protein levels in HL-1 cells . cMyBP-C mRNAs were identified in the ribonucleoprotein complexes immunoprecipitated with anti-Sorbs2 antibodies from cardiomyocyte lysates. Loss of Sorbs2 significantly reduced the half-life of cMyBP-C mRNA (from 2.1 hrs in WT to 1.2 hrs in KO). Co-immunoprecipitation with truncated Sorbs2 constructs showed that the C-terminal SH3 domains of Sorbs2, but not the N-terminal SoHo domain, interacted with cMyBP-C protein. Molecular docking and modeling showed hydrophobic interactions and hydrogen bonds between residues H906 and G907 in the SH3 domain of Sorbs2 and residue A954, P955 and T957 in the SH3-binding motif (949-MA P GA P VT-957) of cMyBP-C with a weighted score of -1036 using ClusPro online service. Conclusions: Sorbs2 regulates cMyBP-C expression through direct interaction with both cMyBP-C mRNA and protein. Loss of Sorbs2 results in reduced cMyBP-C expression, atrial fibrosis, and chamber enlargement, revealing a novel Sorbs2/cMyBP-C axis underlying AFCM pathogenesis.