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Background: Reports show that the left ventricular myocardial work index (LVMWI) is a novel parameter for evaluating cardiac function. Decompensated heart failure leads to a high rate of early mortality in advanced patients with light-chain cardiac amyloidosis (AL-CA) and prevents them from a relatively delayed response to chemotherapy. This study aimed to assess the association of the LVMWI with short-term outcomes and to construct a simple model for risk stratification. Methods: A total of 79 patients with an initial diagnosis of AL-CA were included in this retrospective cohort study. LVMWI was calculated by integrating brachial artery cuff blood pressure and left ventricular longitudinal strain (LVLS). The short-term outcome was defined as 6-month all-cause mortality. Receiver operating characteristic (ROC), logistic regression, and Kaplan-Meier analysis were used in this study. Results: The median follow-up time was 21 months (3-36 months), and 23 (29%) patients died in the first 6 months. The time-dependent ROC and the area under the curve (AUC) showed that the LVMWI had the best predictive potential at the 6-month time point [AUC =0.805; 95% confidence interval (CI): 0.690-0.920]. A bivariate prognostic model based on the LVMWI was constructed, and D-dimer showed a synergistic effect with optimum predicted potential (AUC =0.877; 95% CI: 0.791-0.964). Kaplan-Meier analysis demonstrated that patients with two, one, and none of the variates beyond the cut-off value bore a different risk of 6-month all-cause mortality (accumulated mortality was 86%, 30%, 3%, respectively; log-rank, P<0.001). Multivariate nested logistic regression showed that the level of D-dimer provided an incremental prognostic value (Δχ2=10.3; P=0.001) to the value determined from New York Heart Association (NYHA) classification and the LVMWI. Conclusions: The LVMWI is associated with the short-term outcome of patients with AL-CA. The D-dimer test provides additional prognostic information for the LVMWI.
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BACKGROUND: Light-chain (AL) cardiorenal amyloidosis has been characterized as type 5 cardiorenal syndrome with fluid overload and poor prognosis. Cancer antigen 125 (CA125) has the potential for use in evaluating fluid load and prognosis for heart failure. However, less details for CA125 in AL cardiorenal amyloidosis have been reported. METHODS: Sixty patients diagnosed with AL cardiorenal amyloidosis were enrolled in this retrospective study. Patients were divided into two groups according to the cutoff point of CA125 level (35 U/mL). Logistic regression was used to screen variables associated with CA125. Cox regression analyses was utilized to verify the prognostic potential of CA125. RESULTS: The mean age was 61±8 years, and 68% of the participants were male. Compared to patients with normal CA125 levels (≤35 U/mL), patients with high levels of CA125 (>35 U/mL) had a higher proportion of New York Heart Association class >II, pericardial effusion, and edema, as well as a lower level of albumin and left ventricular longitudinal strain (LVLS). Logistic regression showed age, albumin, and LVLS to be independently associated with CA125. Seventeen (28%) patients died during the follow-up. Multivariate model including CA125, estimated glomerular filtration rate, E/e' and left ventricular ejection fraction showed acceptable prognostic potential (C-index= 0.829, 95%CI 0.749 to 0.909). CA125 remained an independent prognostic factor (HR=1.018, 95%CI 1.005 to 1.031, P=0.008) after adjusting for the remaining three variates and provided a significant incremental effect to the risk determined from them (C-index 0.829 vs 0.784, P=0.037). CONCLUSIONS: Serum CA125 level was associated with long-term prognosis of AL cardiorenal amyloidosis.
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BACKGROUND: Atrial fibrillation (AF) is one of the most prevalent sustained cardiac arrhythmias. The latest studies have revealed a tight correlation between nonalcoholic fatty liver disease (NAFLD) and AF. However, the exact molecular mechanisms underlying the association between NAFLD and AF remain unclear. The current research aimed to expound the genes and signaling pathways that are related to the mechanisms underlying the association between these two diseases. MATERIALS AND METHODS: NAFLD- and AF- related differentially expressed genes (DEGs) were identified via bioinformatic analysis of the Gene Expression Omnibus (GEO) datasets GSE63067 and GSE79768, respectively. Further enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), the construction of a protein-protein interaction (PPI) network, the identification of significant hub genes, and receiver operator characteristic curve analysis were conducted. The gene-disease interactions were analyzed using the Comparative Toxicogenomics Database. In addition, the hub genes were validated by quantitative Real-Time PCR (qRT-PCR) in NAFLD cell model. RESULTS: A total of 45 co-expressed differentially expressed genes (co-DEGs) were identified between the NAFLD/AF and healthy control individuals. GO and KEGG pathway analyses revealed that the co-DEGs were mostly enriched in neutrophil activation involved in the immune response and cytokine-cytokine receptor interactions. Moreover, eight hub genes were selected owing to their high degree of connectivity and upregulation in both the NAFLD and AF datasets. These genes included CCR2, PTPRC, CXCR2, MNDA, S100A9, NCF2, S100A12, and S100A8. CONCLUSIONS: In summary, we conducted the gene differential expression analysis, functional enrichment analysis, and PPI analysis of DEGs in AF and NAFLD, which provides novel insights into the identification of potential biomarkers and valuable therapeutic leads for AF and NAFLD.
Assuntos
Fibrilação Atrial , Hepatopatia Gordurosa não Alcoólica , Fibrilação Atrial/genética , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/genética , Mapas de Interação de Proteínas/genéticaRESUMO
BACKGROUND: The CHADS2 and CHA2DS2-VASc scores are well-established clinical scales to estimate the risk of stroke in patients with atrial fibrillation (AF). However, the predictive power of the two scales concerning left atrial thrombus (LAT) or spontaneous echo contrast (SEC) has not been well investigated. Therefore, we investigated the predict power of CHADS2 and CHA2DS2-VASc scores concerning LAT/SEC; identified clinical, echocardiographic and laboratory predictors of LAT/SEC in addition to the CHADS2 and CHA2DS2-VASc scores; and derived a new scale to predict LAT/SEC accurately, it might improve thromboembolic risk stratification in patients with nonvalvular atrial fibrillation. METHODS: We identified 1102 consecutive AF patients who underwent transesophageal echocardiography (TEE) for the purpose of the exclusion of LAT before catheter ablation, cardioversion or left atrial appendage occlusion. The clinical, echocardiographic and laboratory characteristics of patients were collected from the electronic medical record system. RESULTS: In the study, the prevalence of LAT/SEC was only 4.36%. In the multivariate logistic analysis, hypertension, left atrial enlargement, prior stroke/TIA, left ventricular dysfunction, and renal dysfunction were predictors of LAT/SEC. Receiver operating characteristic curve analysis showed that c-statistics of the CHADS2 and CHA2DS2-VASc scores concerning LAT/SEC were 0.673 and 0.643, respectively. We derived a new scale composed of variables from the multivariate logistic analysis that showed a higher c-statistic value (0.761) than the CHADS2 and CHA2DS2-VASc scores for the prediction of LAT/SEC. CONCLUSION: In our cohort, we found two variables not included in the CHA2DS2-VASc score (renal dysfunction, left atrial enlargement) were independent predictors of LAT/SEC. A new scale combining clinical, echocardiographic and laboratory predictors might improve thromboembolic risk stratification. And there is a great need to carry out a new prospective and multicenter study, with a population more homogenous and including all the determinants for LAT/SEC to establish the independent degree of each variable and the applicability in clinical practice, facilitating the emergence of a new score of thromboembolic risk in patients with nonvalvular atrial fibrillation.