Po-05-161 acquired long qt syndrome in sepsis-induced myocardial injury: investigation on clinical characteristics and mechanism via ion channel reprogramming

Sepsis-induced cardiomyopathy (SIC) is one major cause of death in sepsis. Evidence of various cardiac arrhythmias in septic patients has been reported previously. Acquired QT prolongation (aQTP) is associated with an increased risk of polymorphic VT and Torsade de Pointes. However, data on the clinical analysis of aQTP, or acquired long QT syndrome (aLQTS) in sepsis and their potential mechanism is limited. We aimed to investigate the prevalence and characteristics of aQTP/aLQTS in sepsis and explore the underlying mechanism. Patients diagnosed with sepsis from 2018 to 2022 were enrolled. Occurrence of aQTP as well as cardiac arrhythmias were described. Correlation analysis was performed to investigate associated factors, followed analysis on prognosis. Mouse model for SIC was thereafter established, in which bulk-RNA sequencing of the heart was performed. The gene expression of myocardial tissue was then determined by RT-quantitative polymerase chain reaction. Biostatistical analysis based on Gene Expression Omnibus database were performed. Among 110 patients diagnosed with sepsis, aQTP was found in 13 (11.8%) subjects with a mean QTc of 502 msec, in which 2 typical aLQTS cases with progressive QTP was observed to develop electrical storm during sepsis following pacemaker implantation and esophagectomy, respectively. In correlation analysis, the prevalence of aQTP was found statistically associated with heart failure (p=0.009) and all-cause shock (p=0.02). As for primary endpoints, aLQTS was shown relevant with the length of ICU stay (p=0.037) and as an independent risk factor for all-cause death (p=0.026) in sepsis. Sequencing of myocardium on SIC mice revealed multiple genes associated with electrical ion channels were significantly altered in SIC, e.g., KCNQ1 (p<0.001, R2=0.84), KCNJ5(p<0.001, R2=0.97), SCN5A (p<0.001, R2=0.86), CALMl4 (p-0038, R2=0.36) etc., which affect cardiac repolarization by regulating potassium, sodium and calcium channels, and was in accordance with the results of qPCR for the hub genes. Externally validation based on GEO database demonstrated similar results. aQTP is not infrequently observed in sepsis-induced myocardial injury, which is associated with poor prognosis in septic patients. It requires more clinical awareness of regular monitoring for related aLQTS and other complications. Sepsis-induced myocardial inflammation may have an impact on the expression of multiple genes related to myocardial repolarization.