Background: Diabetes mellitus is an important risk factor for atrial fibrillation (AF) development. Sodium–glucose co-transporter-2 (SGLT-2) inhibitors are used for the treatment of type 2 diabetes mellitus (T2DM). Their cardioprotective effects have been reported but whether they prevent AF in T2DM patients are less well-explored. We tested the hypothesis that the SGLT-2 inhibitor, empagliflozin, can prevent atrial remodeling in a diabetic rat model. Methods: High-fat diet and low-dose streptozotocin (STZ) treatment were used to induce T2DM. A total of 96 rats were randomized into the following four groups: (i) control (ii) T2DM, (iii) low-dose empagliflozin (10 mg/kg/day)/T2DM; and (iv) high-dose empagliflozin (30 mg/kg/day)/T2DM by the intragastric route for 8 weeks. Results: Compared with the control group, left atrial diameter, interstitial fibrosis and the incidence of AF inducibility were significantly increased in the DM group. Moreover, atrial mitochondrial respiratory function, mitochondrial membrane potential, and mitochondrial biogenesis were impaired. Empagliflozin treatment significantly prevented the development of these abnormalities in DM rats, likely via the peroxisome proliferator-activated receptor-c coactivator 1α (PGC-1α)/nuclear respiratory factor-1 (NRF-1)/mitochondrial transcription factor A (Tfam) signaling pathway. Conclusions: Empagliflozin can ameliorate atrial structural and electrical remodeling as well as improve mitochondrial function and mitochondrial biogenesis in T2DM, hence may be potentially used in the prevention of T2DM-related atrial fibrillation.

Heart failure (HF) is a major epidemic with rising morbidity and mortality rates that encumber global healthcare systems. While some studies have demonstrated the value of CRP in predicting (i) the development of HFpEF and (ii) long-term clinical outcomes in HFpEF patients, others have shown no such correlation. As a result, we conducted the following systematic review and meta-analysis to assess both the diagnostic and prognostic role of CRP in HFpEF. PubMed and Embase were searched for studies that assess the relationship between CRP and HFpEF using the following search terms: (((C-reactive protein) AND ((preserved ejection fraction) OR (diastolic heart failure))). The search period was from the start of database to August 6, 2019, with no language restrictions. A total of 312 and 233 studies were obtained from PubMed and Embase respectively, from which 19 studies were included. Our meta-analysis demonstrated the value of a high CRP in predicting the development of not only new onset HFpEF (HR: 1.08; 95% CI: 1.00–1.16; P = 0.04; I² = 22%), but also an increased risk of cardiovascular mortality when used as a categorical (HR: 2.52; 95% CI: 1.61–3.96; P < 0.0001; I² = 19%) or a continuous variable (HR: 1.24; 95% CI: 1.04–1.47; P = 0.01; I² = 28%), as well as all-cause mortality when used as a categorical (HR: 1.78; 95% CI: 1.53–2.06; P < 0.00001; I² = 0%) or a continuous variable: (HR: 1.06; 95% CI: 1.02–1.06; P = 0.003; I² = 61%) in HFpEF patients. CRP can be used as a biomarker to predict the development of HFpEF and long-term clinical outcomes in HFpEF patients, in turn justifying its use as a simple, accessible parameter to guide clinical management in this patient population. However, more prospective studies are still required to not only explore the utility and dynamicity of CRP in HFpEF but also to determine whether risk stratification algorithms incorporating CRP actually provide a material benefit in improving patient prognosis.

Brugada syndrome (BrS) is an inherited ion channel channelopathy predisposing to ventricular arrhythmias and sudden cardiac death. Originally believed to be predominantly associated with mutations in SCN5A encoding for the cardiac sodium channel, mutations of 18 genes other than SCN5A have been implicated in the pathogenesis of BrS to date. Diagnosis is based on the presence of a spontaneous or drug-induced coved-type ST segment elevation. The predominant electrophysiological mechanism underlying BrS remains disputed, commonly revolving around the three main hypotheses based on abnormal repolarization, depolarization or current-load match. Evidence from computational modelling, pre-clinical and clinical studies illustrates that molecular abnormalities found in BrS lead to alterations in excitation wavelength (λ), which ultimately elevates arrhythmic risk. A major challenge for clinicians in managing this condition is the difficulty in predicting the subset of patients who will suffer from life-threatening ventricular arrhythmic events. Several repolarization risk markers have been used thus far, but these neglect the contributions of conduction abnormalities in the form of slowing and dispersion. Indices incorporating both repolarization and conduction based on the concept of λ have recently been proposed. These may have better predictive values than the existing markers. Current treatment options include pharmacological therapy to reduce the occurrence of arrhythmic events or to abort these episodes, and interventions such as implantable cardioverter-defibrillator insertion or radiofrequency ablation of abnormal arrhythmic substrate.

Background: Coronavirus disease 2019 (COVID‐19) primarily causes lung infection, but recent studies have shown that cardiac involvement is associated with a worse prognosis.Objectives: We conducted a systematic review and meta‐analysis to examine the prevalence of cardiac arrhythmias detected by the electrocardiogram and their relationships with adverse outcomes in patients with COVID‐19.Methods: PubMed and Google were searched for studies that reported on cardiac arrhythmias and/or examined the relationship between arrhythmias and adverse outcomes.Results: Thirty studies with 12,713 participants were included in the systematic review, and 28 studies (n = 12,499) in the meta‐analysis. The mean age was 61.3 ± 16.8 years; 39.3% were female. In 25 studies with 7578 patients, the overall prevalence of cardiac arrhythmias was 10.3% (95% confidence interval [CI]: 8.4%–12.3%). The most common arrhythmias documented during hospitalization were supraventricular arrhythmias (6.2%, 95% CI: 4.4%–8.1%) followed by ventricular arrhythmias (2.5%, 95% CI: 1.8%–3.1%). The incidence of cardiac arrhythmias was higher among critically ill patients (relative risk [RR]: 12.1, 95% CI: 8.5–17.3) and among non‐survivors (RR: 3.8, 95%, CI: 1.7–8.7). Eight studies reported changes in the QT interval. The prevalence of QTc > 500 ms was 12.3% (95% CI: 6.9%–17.8%). ST‐segment deviation was reported in eight studies, with a pooled estimate of 8.7% (95% CI: 7.3% to 10.0%).Conclusion: Our meta‐analysis showed that QTc prolongation, ST‐segment deviation, and various other cardiac arrhythmias were observed in patients hospitalized with COVID‐19. The presence of cardiac arrhythmias was associated with a worse prognosis.

The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) vs dipeptidyl peptidase-4 inhibitors (DPP4I) on the risk of new-onset gout remains unknown. This study aims to compare the effects of SGLT2I against DPP4I on gout risks. This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus treated with SGLT2I or DPP4I between January 1^st, 2015 and December 31^st, 2020 in Hong Kong. The study outcomes are new-onset gout and all-cause mortality. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I was performed. Univariable and multivariable Cox regression analysis models were conducted. Competing risks models and multiple approaches based on the propensity score were applied. This study included 43201 patients (median age: 63.23 years old [Interquantile range, IQR]: 55.21–71.95, 53.74% males; SGLTI group: n = 16144; DPP4I group: n = 27057) with a median follow-up of 5.59 years (IQR: 5.27–5.81 years) since initial drug exposure. The incidence rate of developing gout (Incidence rate [IR]: 2.5; 95% CI: 2.2–2.9) among SGLT2I users was significantly lower than DPP4I users (IR: 5.2; 95% CI: 4.8–5.8). SGLT2 was associated with 51% lower risks of gout (HR: 0.49; 95% CI: 0.42–0.58; P-value < 0.0001) and 51% lower risks of all-cause mortality (HR: 0.49; 95% CI: 0.42–0.58; P-value < 0.0001) after adjusting for significant demographics, past comorbidities, medications, and laboratory results. The results remained consistent on competing risk and other propensity score approaches. SGLT2I use was associated with lower risks of new gout diagnosis compared with DPP4I use.