The role of circulating biomarkers in predicting the 30-day mortality of immune checkpoint inhibitors-related myocarditis: a retrospective cohort study.

Immune checkpoint inhibitors-related myocarditis (ICIs-M) is a rare and highly lethal immune-related adverse events (irAEs) in common irAEs. This study aims to find circulating biomarkers that can reflect disease state and prognosis accurately. 48 patients with ICIs-M were enrolled according to the diagnostic criteria for ICIs-related myocarditis. For all enrolled patients, valuable information was extracted retrospectively from the medical system, mainly including demographic information, tumor information and laboratory examination. The follow-up period was defined as 30 days after the first diagnosis of ICIs-M. In this study, the 30-day mortality rate of ICIs-M was 24.4%. After adjusting for potential confounding factors using multivariate analysis tools, we demonstrated the excellent performance of biomarkers in predicting 30-day mortality in patients with ICIs-M, including PLT (hazard ratio (HR), 1.07; 95% confidence interval (95%CI), 1.01-1.14; p = 0.028), ALT (HR, 1.23; 95%CI, 1.06-1.41; p = 0.005), AST(HR, 1.06; 95%CI, 1.01-1.10; p = 0.015), LDH (HR, 1.15; 95%CI, 1.04-1.26; p = 0.004), troponin I(HR, 1.44; 95%CI, 1.09-1.89; p = 0.009), PLR (blood plate/lymphocyte) (HR, 1.04; 95% CI, 1.01-1.07; p = 0.024), LAR (lactate dehydrogenase/albumin) (HR, 1.05; 95%CI, 1.01-1.09; p = 0.012), and AAR (aspartate transaminase/albumin) (HR, 1.18; 95%CI, 1.00-1.39; p = 0.048). The analysis of the receiver operating characteristic showed that biomarkers with area under curve (AUC) greater than or equal to 0.80 were LDH (cutoff value, 724.5; AUC, 0.86; 95%CI, 0.75-0.97), LAR (cutoff value, 18.11; AUC, 0.87; 95%CI, 0.76-0.97), troponin I (cutoff value, 0.87; AUC, 0.80; 95%CI, 0.62-0.99), and AAR(cutoff value, 1.52; AUC, 0.80; 95%CI, 0.61-0.98). LDH, LAR, troponin I, and AAR are a group of promising biomarkers that demonstrate excellent predictive ability in predicting the 30-day mortality rate of immune-related myocarditis.

Screening and Bioinformatics Analysis of Crucial Gene of Heart Failure and Atrial Fibrillation Based on GEO Database.

Background and objectives: In clinical practice, we observed that the prognoses of patients with heart failure and atrial fibrillation were worse than those of patients with only heart failure or atrial fibrillation. The study aims to get a better understanding of the common pathogenesis of the two diseases and find new therapeutic targets. Materials and Methods: We downloaded heart failure datasets and atrial fibrillation datasets from the gene expression omnibus database. The common DEGs (differentially expressed genes) in heart failure and atrial fibrillation were identified by a series of bioinformatics methods. To better understand the functions and possible pathways of DEGs, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: We identified 22 up-regulated genes and 14 down-regulated genes in two datasets of heart failure and 475 up-regulated and 110 down-regulated genes in atrial fibrillation datasets. In addition, two co-upregulated (FRZB, SFRP4) and three co-downregulated genes (ENTPPL, AQP4, C1orf105) were identified. GO enrichment results showed that these common differentially expressed genes were mainly concentrated in the signal regulation of the Wnt pathway. Conclusions: We found five crucial genes in heart failure and atrial fibrillation, which may be potential therapeutic targets for patients with heart failure and atrial fibrillation.

Matrix Metalloproteinases Increase Because of Hypoperfusion in Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: Myocardial fibrosis (MF) is considered a result of microvascular dysfunction in patients with hypertrophic cardiomyopathy. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), capable of degrading collagen, directly participate in the development of MF. First we investigated the relationships among MF, microvascular rarefaction, and MMPs. Then we assessed the prognostic value of MF-related circulating biomarkers. METHODS: Fifty-five obstructive hypertrophic cardiomyopathy (HOCM) patients were enrolled after surgical myectomy. Myocardial samples were performed with Masson's trichrome staining and immunohistochemical procedures for collagen volume fraction and microvascular density, respectively. Enzyme-linked immunosorbent assays were used to assess myocardial and plasma of MMP-2, MMP-9, and TIMP-1 and plasma C-terminal propeptide of procollagen type Ⅰ (PICP) and C-terminal telopeptide of type Ⅰ collagen (ICTP) levels. The composite cardiovascular endpoint consisted of new-onset atrial fibrillation, heart failure requiring hospitalization, and all-cause death. RESULTS: In HOCM patients microvascular density was associated with the myocardial MMP-2/TIMP-1 ratio (r = -0.348, P = .009), whereas no correlation was found between collagen volume fraction and myocardial MMPs. During the 44-month follow-up 6 patients experienced a cardiovascular endpoint. The plasma PICP/ICTP ratio and MMP-2/TIMP-1 ratio were the 2 strongest prognostic makers. In multivariable analyses high PICP/ICTP and MMP-2/TIMP-1 ratios remained independent predictors of cardiovascular outcomes after adjusting for clinical confounders (hazard ratios, 12.683 [P = .021] and 17.037 [P = .027], respectively). CONCLUSIONS: In HOCM patients the myocardial MMP-2/TIMP-1 ratio was elevated because of microvascular rarefaction but may not be responsible for MF. High plasma PICP/ICTP and MMP-2/TIMP-1 ratios are independent predictors of adverse outcomes in HOCM patients.

Quantitative fragmented QRS has a good diagnostic value on myocardial fibrosis in hypertrophic obstructive cardiomyopathy based on clinical-pathological study.

BACKGROUND: To investigate the relationship between fragmented QRS (fQRS) quantified by a new method and myocardial fibrosis (MF) and the diagnostic value of quantitative fQRS (Q-fQRS) to detect MF in hypertrophic obstructive cardiomyopathy (HOCM) patients based on histological validation. METHODS: We performed a retrospective study that included 69 patients with HOCM who underwent ventricular septal surgery. Nine individuals who died from accidents were studied as a control reference for the histological parameters. Septal myocardium samples were subjected to Masson's trichrome staining to quantify the collagen volume fraction (CVF). An fQRS pattern was defined as the presence of additional R waves or RSR', evidenced by notched R or S wave on electrocardiography (ECG). The Q-fQRS was quantified as the total amount of deflections in the QRS complex in all 12 routine ECG leads together. Cardiac magnetic resonance imaging was conducted, and late gadolinium enhancement (LGE) was measured at 2, 4, 6 and 8 standard deviations (SDs). RESULTS: Of the 69 patients, fQRS was documented in 38 (55.1%) patients, the mean number of leads with fQRS was 3.7 ± 1.6, and the mean Q-fQRS was 17 ± 7.2. Compared with HOCM patients without fQRS, HOCM patients with fQRS had a higher CVF and more LGE at 6 SD (P < 0.001; P = 0.040). Q-fQRS was correlated with CVF (r = 0.640, P < 0.001), and Q-fQRS showed the best correlation with LGE measured at 8 SD (r = 0.379, P = 0.002). Multivariate regression analyses revealed that Q-fQRS was independently associated with the extent of CVF in HOCM patients after adjusting for age, sex, body surface area and the extent of LGE at 6 SD (P < 0.001). When the patients were divided into subgroups with normal CVF or high CVF according to the CVF in controls, Q-fQRS and LGE at 6SD showed similar diagnostic value in detecting patients with high CVF, with sensitivities of 66.7% vs 68.6%, specificities of 76.7% vs 72.4%, and accuracies of 71% vs 70.3%. CONCLUSIONS: HOCM patients with fQRS showed more extensive MF. Q-fQRS was an independent predictor for MF and had a good diagnostic value, with a sensitivity of 66.7% and specificity of 76.7%, in identifying patients with higher fibrotic burden.