The association between serum chloride and mortality in ICU patients with heart failure: The impact of bicarbonate.

OBJECTIVE: To assess whether serum chloride predicts risk of death in intensive care unit (ICU) patients with heart failure (HF) and the effect of bicarbonate on the efficacy of serum chloride in predicting risk of death in ICU patients. METHODS: A total of 9364 HF patients hospitalized in the ICU were enrolled. Patients were divided into hypochloremia (< 96 mEq/L), normal chloride (96-108 mEq/L), and hyperchloremia (> 108 mEq/L) groups. Similarly, we divided the serum bicarbonate level into three groups: low bicarbonate (< 22 mEq/L), medium bicarbonate (22-26 mEq/L), and high bicarbonate (> 26 mEq/L). The outcome of this study was in-hospital mortality. Then, we analyzed the association between abnormal serum chloride and mortality according to the category of serum bicarbonate and assessed the interaction effect. Restricted cubic spline (RCS) was used to show possible nonlinear associations. RESULTS: In the overall study population, hypochloremia was associated with a higher risk of in-hospital mortality than normal chloride (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.26-1.86, P < 0.001), hyperchloremia was not significantly related to in-hospital mortality (OR 1.00, 95% CI 0.85-1.19, P = 0.962). However, a linear association between serum chloride and in-hospital mortality was found in the low and normal bicarbonate groups (all P for nonlinear >0.05). CONCLUSIONS: Hypochloremia is associated with in-hospital mortality and longer hospital stay in critically ill patients with HF. In addition, risk of death in the low and medium serum bicarbonate groups decreased with increasing serum chloride level.

Systemic Bioinformatic Analyses of Nuclear-Encoded Mitochondrial Genes in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease and mitochondria plays a key role in the progression in HCM. Here, we analyzed the expression pattern of nuclear-encoded mitochondrial genes (NMGenes) in HCM and found that the expression of NMGenes was significantly changed. A total of 316 differentially expressed NMGenes (DE-NMGenes) were identified. Pathway enrichment analyses showed that energy metabolism-related pathways such as "pyruvate metabolism" and "fatty acid degradation" were dysregulated, which highlighted the importance of energy metabolism in HCM. Next, we constructed a protein-protein interaction network based on 316 DE-NMGenes and identified thirteen hubs. Then, a total of 17 TFs (transcription factors) were predicted to potentially regulate the expression of 316 DE-NMGenes according to iRegulon, among which 8 TFs were already found involved in pathological hypertrophy. The remaining TFs (like GATA1, GATA5, and NFYA) were good candidates for further experimental verification. Finally, a mouse model of transverse aortic constriction (TAC) was established to validate the genes and results showed that DDIT4, TKT, CLIC1, DDOST, and SNCA were all upregulated in TAC mice. The present study represents the first effort to evaluate the global expression pattern of NMGenes in HCM and provides innovative insight into the molecular mechanism of HCM.

Brugada syndrome with SCN5A mutations exhibits more pronounced electrophysiological defects and more severe prognosis: A meta-analysis.

Whether the presence of SCN5A mutation is a predictor of BrS risk remains controversial, and patient selection bias may have weakened previous findings. Therefore, we performed this study to clarify the clinical characteristics and outcomes of BrS probands with SCN5A mutations. We systematically retrieved eligible studies published through October 2018. A total of 17 studies enrolling 1780 BrS patients were included. Overall, our results found that compared with BrS patients without SCN5A mutations, patients with SCN5A mutations exhibited a younger age at the onset of symptoms and higher rate of the spontaneous type-1 electrocardiogram pattern, more pronounced conduction or repolarization abnormalities, and increased atrial vulnerability. In addition, the presence of SCN5A mutations was associated with an elevated risk of major arrhythmic events in both Asian (odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.07-3.11; P = .03) and Caucasian (OR = 2.24, 95% CI 1.02-4.90; P = .04) populations. In conclusions, patients with SCN5A mutations exhibit more pronounced electrophysiological defects and more severe prognosis. Clinicians should be cautious when utilizing genetic testing for risk stratification or treatment guidance before determining whether the causal relationship regarding SCN5A mutation status is an independent predictor of risk.

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Asians With Nonvalvular Atrial Fibrillation: A Network Meta-Analysis.

There are few head-to-head trials directly comparing non-vitamin K antagonist oral anticoagulants (NOACs) against one other. A network meta-analysis (NMA) was performed to examine the indirect comparisons among NOACs in Asians with nonvalvular atrial fibrillation (NVAF). STATA 15.0 and ADDIS 1.16.8 softwares were used to perform the statistical analysis. Odds ratios with 95% credible intervals were applied to evaluate the end points. The probabilities of treatment rank were used to understand which interventions are more effective and safe, and the total rank probability was 1. In our NMA, the rank probabilities of apixaban in the case of stroke or systemic embolism, death from any cause, major bleeding, and intracranial hemorrhage (ICH) were 0.47, 0.49, 0.42, and 0.51, respectively. For cases of myocardial infarction, the rank probabilities of rivaroxaban were 0.40. This NMA indirectly compares the main efficacy and safety end points among NOACs in Asians with NVAF, and the rank probability analysis showed that apixaban likely performs best in cases of stroke or systemic embolism, death from any cause, and ICH; rivaroxaban may have the best performance for myocardial infarction.

The relationship between vitamin D and risk of atrial fibrillation: a dose-response analysis of observational studies.

BACKGROUND: The relationship between serum vitamin D and atrial fibrillation (AF) or postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass graft (CABG) is still debated. It is also unclear whether there is a dose-response relationship between circulating vitamin D and the risk of AF or POAF. METHODS: The Cochrane Library, PubMed, and Embase databases were searched for relevant studies. We used a "one-stage approach" with a restricted cubic spline model to summarize the dose-specific relationships between serum vitamin D and AF. Relative risk (RR) was used to measure the effects in this meta-analysis. RESULTS: In total, 13 studies were included with a total of 6519 cases of AF among 74,885 participants. Vitamin D deficiency (< 20 ng/ml) was associated with increased risks of AF (RR: 1.23, 95% CI: 1.05-1.43). In the dose-response analysis, the summary RR for a 10 ng/ml increased in vitamin D was 0.88 (95% CI: 0.78-0.98) and there was no evidence of a non-linear association, Pnon-linearity = 0.86. In the age subgroup, high vitamin D (per 10 ng/ml increase) reduced the risk of AF in the older group (> 65 years) (RR = 0.68, 95% CI = 0.52-0.89) but not among young individuals (< 65 years) (RR = 0.87, 95% CI = 0.72-1.06). In addition, a strong association was found between a 10 ng/ml increased in vitamin D and POAF incident in the patient after CABG (RR: 0.44, 95% CI: 0.24-0.82). CONCLUSION: Our dose-response meta-analysis suggested serum vitamin D deficiency was associated with an increased risk of AF in the general population and POAF in patients after CABG. Further studies are needed to explore the age difference in the association between serum vitamin D level and the risk of AF and whether vitamin D supplements will prevent AF. TRIAL REGISTRATION: This study has been registered with PROSPERO (International prospective register of systematic reviews)-registration number-CRD42019119258.