Medium-Term Prognostic Implications of Cardiac Magnetic Resonance Imaging in Patients With Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): A Systematic Review and Meta-Analysis.

BACKGROUND: This study aimed to evaluate the medium-term prognostic implications of cardiac magnetic resonance (CMR) imaging in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA). METHODS: A systematic literature search of Embase, PubMed, and The Cochrane Library was performed. Eligible studies reported outcomes of CMR-assessed MINOCA with a mean follow-up period of >6 months. The primary endpoint was all-cause death. Secondary endpoints included cardiac death, reinfarction, and cardiovascular rehospitalisation. The pooled effect sizes with 95% confidence interval (CIs) were estimated using a random effect model. RESULTS: A total of 3,050 patients from twenty-one studies were included in the meta-analysis. The prevalence of myocarditis, "true" myocardial infarction, Takotsubo cardiomyopathy, and normal CMR imaging was 36%, 25%, 14%, and 19%, respectively. Pooled data showed that the annualised event rates for all-cause mortality, cardiac mortality, reinfarction, and cardiovascular rehospitalisation were 1.01% (95% CI 0.59%-1.51%), 0.06% (95% CI 0.00%-0.39%), 0.68% (95% CI 0.18%-1.38%), and 5.67% (95% CI 3.11%-8.85%), respectively. Compared with patients with a diagnosis of myocarditis on CMR, patients with Takotsubo cardiomyopathy (RR 7.11; 95% CI 3.04-16.66) and "true" myocardial infarction (RR 3.82; 95% CI 1.65-8.86) were associated with a significantly higher risk of all-cause mortality, whereas a similar risk of all-cause mortality was observed in patients with normal imaging (RR 1.01; 95% CI 0.28-3.59). No association was found between CMR diagnoses and the risk of secondary endpoints in MINOCA. CONCLUSIONS: In patients with MINOCA assessed by CMR, the overall absolute incidence rates of mortality and reinfarction were low. However, certain imaging diagnoses were associated with a higher risk of all-cause mortality, with most deaths attributed to non-cardiac causes. Additionally, these patients experienced a high burden of cardiovascular rehospitalisation. REGISTRATION: PROSPERO (CRD42022323615).

Association between short-term systemic use of glucocorticoids and prognosis of cardiogenic shock: a retrospective analysis.

OBJECTIVE: To investigate the prescription rate of short-term systemic use of glucocorticoids during hospitalization in patients with cardiogenic shock (CS), and outcomes related with glucocorticoid use. METHODS: We extracted patients' information from the Medical Information Mart for Intensive Care IV version 2.0 (MIMIC-IV v2.0) database. The primary endpoint was 90-day all-cause mortality. Secondary safety endpoints were infection identified by bacterial culture and at least one episode of hyperglycemia after ICU admission. Propensity score matching (PSM) was used to balance baseline characteristics. The difference in cumulative mortality rate between these treated with and without glucocorticoids was assessed by Kaplan-Meier curve with log-rank test. Independent risk factors for endpoints were identified by Cox or Logistic regression analysis. RESULTS: A total of 1528 patients were enrolled, and one-sixth of these patients received short-term systemic therapy of glucocorticoids during hospitalization. These conditions, including rapid heart rate, the presence of rheumatic disease, chronic pulmonary disease and septic shock, high lactate level, the requirements of mechanical ventilation and continuous renal replacement therapy, were associated with an increase in glucocorticoid administration (all P ≤ 0.024). During a follow-up of 90 days, the cumulative mortality rate in patients treated with glucocorticoids was significantly higher than that in these untreated with glucocorticoids (log-rank test, P < 0.001). Multivariable Cox regression analysis showed that glucocorticoid use (hazard ratio 1.48, 95% confidence interval [CI] 1.22-1.81; P < 0.001) was independently associated with an increased risk for 90-day all-cause mortality. This result was consistent irrespective of age, gender, the presence of myocardial infarction, acute decompensated heart failure and septic shock, and inotrope therapy, but was more evident in low-risk patients as assessed by ICU scoring systems. Additionally, multivariable Logistic regression analysis showed that glucocorticoid exposure was an independent predictor of hyperglycemia (odds ratio 2.14, 95% CI 1.48-3.10; P < 0.001), but not infection (odds ratio 1.23, 95% CI 0.88-1.73; P = 0.221). After PSM, glucocorticoid therapy was also significantly related with increased risks of 90-day mortality and hyperglycemia. CONCLUSIONS: Real-world data showed that short-term systemic use of glucocorticoids was common in CS patients. Importantly, these prescriptions were associated with increased risks of adverse events.

SNAP-25/syntaxin 1A complex functionally modulates neurotransmitter gamma-aminobutyric acid reuptake.

Neurotransmitter gamma-aminobutyric acid (GABA) release to the synaptic clefts is mediated by the formation of a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, which includes two target SNAREs syntaxin 1A and SNAP-25 and one vesicle SNARE VAMP-2. The target SNAREs syntaxin 1A and SNAP-25 form a heterodimer, the putative intermediate of the SNARE complex. Neurotransmitter GABA clearance from synaptic clefts is carried out by the reuptake function of its transporters to terminate the postsynaptic signaling. Syntaxin 1A directly binds to the neuronal GABA transporter GAT-1 and inhibits its reuptake function. However, whether other SNARE proteins or SNARE complex regulates GABA reuptake remains unknown. Here we demonstrate that SNAP-25 efficiently inhibits GAT-1 reuptake function in the presence of syntaxin 1A. This inhibition depends on SNAP-25/syntaxin 1A complex formation. The H3 domain of syntaxin 1A is identified as the binding sites for both SNAP-25 and GAT-1. SNAP-25 binding to syntaxin 1A greatly potentiates the physical interaction of syntaxin 1A with GAT-1 and significantly enhances the syntaxin 1A-mediated inhibition of GAT-1 reuptake function. Furthermore, nitric oxide, which promotes SNAP-25 binding to syntaxin 1A to form the SNARE complex, also potentiates the interaction of syntaxin 1A with GAT-1 and suppresses GABA reuptake by GAT-1. Thus our findings delineate a further molecular mechanism for the regulation of GABA reuptake by a target SNARE complex and suggest a direct coordination between GABA release and reuptake.

Morphine withdrawal increases glutamate uptake and surface expression of glutamate transporter GLT1 at hippocampal synapses.

Opiate abuse causes adaptive changes in several processes of synaptic transmission in which the glutamatergic system appears a critical element involved in opiate tolerance and dependence, but the underlying mechanisms remain unclear. In the present study, we found that glutamate uptake in hippocampal synaptosomes was significantly increased (by 70% in chronic morphine-treated rats) during the morphine withdrawal period, likely attributable to an increase in the number of functional glutamate transporters. Immunoblot analysis showed that expression of GLT1 (glutamate transporter subtype 1) was identified to be upregulated in synaptosomes but not in total tissues, suggesting a redistribution of glutamate transporter expression. Moreover, the increase in glutamate uptake was reproduced in cultured neurons during morphine withdrawal, and the increase of uptake in neurons could be blocked by dihydrokainate, a specific inhibitor of GLT1. Cell surface biotinylation and immunoblot analysis showed that morphine withdrawal produced an increase in GLT1 expression rather than EAAC1 (excitatory amino acids carrier 1), a neuronal subtype, at the cultured neuronal cell surface, whereas no significant change was observed in that of cultured astrocytes. Electron microscopy also revealed that GLT1 expression was markedly increased in the nerve terminals of hippocampus and associated with the plasma membrane in vivo. These results suggest that GLT1 in hippocampal neurons can be induced to translocate to the nerve terminals and express on the cell surface during morphine withdrawal. The translocation of GLT1 at synapses during morphine withdrawal provides a neuronal mechanism for modulation of excitatory neurotransmission during opiate abuse.