Daily Cardiology Research Analysis

Acute myocardial infarction remains a leading cause of morbidity and mortality worldwide. Pharmacogenetic and chronotherapeutic approaches are increasingly applied to optimize therapy in chronic cardiovascular diseases. While gene variants are known to influence long-term drug efficacy, their role in modulating drug-induced cardioprotection in acute conditions such as myocardial infarction is unclear. Similarly, the impact of circadian timing on cardioprotective responses remains insufficiently defined. To address these questions, we evaluated metoprolol as a model cardioprotective agent. Here we examine, in a non-pre-specified exploratory analysis of the METOCARD-CNIC trial (NCT01311700), the influence of ADRB1 Arg389Gly polymorphism and the time of AMI onset on metoprolol efficacy. We found that metoprolol reduced infarct size only in patients homozygous for the ADRB1 Arg389 allele, consistent with its genotype-dependent inhibition of neutrophil migration. In-silico docking and binding studies revealed unstable interactions of metoprolol with the Gly389 variant of ADRB1. Moreover, metoprolol was associated with reduced infarct size when AMI onset occurred between 6:00 and 12:00 h. Restricted cardioprotection to the light phase was confirmed in male mice and in neutrophil-specific Adrb1-knockout models. Collectively, these findings highlight the critical roles of genetic background and circadian timing in shaping the efficacy of acute cardioprotective therapies, supporting the rationale for personalized interventions in acute myocardial infarction.

BACKGROUND: Subintimal tracking and re-entry (STAR) with staged stenting may increase the success and safety of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) when used as a bailout strategy. The optimal timing for staged stenting is unknown. OBJECTIVES: In this study, the authors sought to evaluate the timing of staged PCI after STAR by randomizing to an earlier (5-7 weeks) or later (12-14 weeks) timeframe. METHODS: Patients undergoing CTO PCI with the use of STAR (n = 150) were randomized at 6 centers to early or late staged PCI. The primary endpoint was partial technical success of the staged procedure, defined as TIMI flow grade 2-3 with <30% residual stenosis into at least 1 ≥2.5 mm distal branch. Study outcomes were compared between groups with the use of chi-square and Fisher exact tests. RESULTS: Seventy-three patients were randomized to the early group and 77 to the late group. The mean Japanese-CTO score was 2.9 ± 1.1. Differences in the primary endpoint between the early group and the late group did not reach statistical significance (83.6% vs 71.4%; P = 0.08). TIMI flow grade 2-3 in the target vessel at the start of staged procedure was higher in the early group (64.4% vs 44.2%; P = 0.012; P = 0.048 after adjustment). CONCLUSIONS: Among patients undergoing STAR with deferred stenting after an unsuccessful index CTO PCI attempt, the partial technical success rate of staged procedures was high. Although vessel patency was higher at the start of early staged procedures, there were no statistically significant differences for partial technical success of the staged procedure with early or late treatment. (STAR and Deferred Stenting Study [STAR]; NCT05089864).

The activation of blood monocytes and the infiltration of monocyte-derived macrophages into the vessel walls are the central part of atherosclerosis. However, the mechanisms underlying the processes remain unclear. Here, we report that G-protein signaling modulator 1 (GPSM1) plays a critical role in atherogenesis. We found that GPSM1 expression in lesional macrophages was increased during atherosclerosis development both in mice and humans. Myeloid-specific GPSM1 ablation protects mice against atherosclerosis and reduces aortic inflammation in both