Background: The meta-analysis of randomized controlled trials has illustrated that the efficacy of low-dose non-vitamin K antagonist oral anticoagulants is inferior compared with standard-dose non-vitamin K antagonist oral anticoagulants, though they are still frequently prescribed for Asian patients with non-valvular atrial fibrillation. We aimed to further investigate the efficacy and safety of low-dose non-vitamin K antagonist oral anticoagulants by carrying out a meta-analysis of all relevant randomized controlled trials and cohort studies.

Methods: Cochrane Central Register of Controlled Trials, Embase, and MEDLINE were systematically searched from the inception to September 9, 2021, for randomized controlled trials or cohorts that compared the efficacy and/or safety of low-dose non-vitamin K antagonist oral anticoagulants in Asian patients with non-valvular atrial fibrillation. The primary outcomes were stroke and major bleeding, and the secondary outcomes were mortality, intracranial hemorrhage, and gastrointestinal hemorrhage. Hazard ratios and 95% CIs were estimated using the random-effect model.

Results: Nineteen publications involving 371 574 Asian patients with non-valvular atrial fibrillation were included. Compared with standard-dose non-vitamin K antagonist oral anticoagulants, low-dose non-vitamin K antagonist oral anticoagulants showed comparable risks of stroke (hazard ratio, 1.18; 95% CI 0.98 to 1.42), major bleeding (hazard ratio, 1.00; 95% CI 0.83 to 1.21), intracranial hemorrhage (hazard ratio, 1.13; 95% CI 0.92 to 1.38), and gastrointestinal hemorrhage (hazard ratio, 1.07; 95% CI 0.87 to 1.31), though had a higher risk of mortality (hazard ratio, 1.34; 95% CI 1.05 to 1.71). Compared with warfarin, low-dose non-vitamin K antagonist oral anticoagulants were associated with lower risks of stroke (hazard ratio, 0.73; 95% CI 0.67 to 0.79), mortality (hazard ratio, 0.69; 95% CI 0.60 to 0.81), major bleeding (hazard ratio, 0.62; 95% CI 0.51 to 0.75), intracranial hemorrhage (hazard ratio, 0.48; 95% CI 0.33 to 0.69), and gastrointestinal hemorrhage (hazard ratio, 0.78; 95% CI 0.65 to 0.93).

Conclusion: Low-dose non-vitamin K antagonist oral anticoagulants were superior to warfarin, and comparable to standard-dose non-vitamin K antagonist oral anticoagulants considering risks of stroke, major bleeding, intracranial hemorrhage, and gastrointestinal hemorrhage. Further, high qualified studies are warranted.

Background: Although current guidelines recommend ticagrelor to clopidogrel for patients with acute coronary syndrome, its benefit and risk are unclear for East Asians. This meta-analysis was performed to assess the efficacy and safety of ticagrelor in East Asian patients with acute coronary syndrome.

Methods: Medline, EMBASE, and Cochrane Databases were searched from inception to July, 2021, for randomized controlled trials comparing ticagrelor with clopidogrel in East Asian patients with acute coronary syndrome. Major adverse cardiovascular events and bleeding events were assessed by using Mantel-Haenszel-pooled risk ratio and 95% confidence interval.

Results: Five randomized controlled trials identified 2752 patients with acute coronary syndrome. Compared with clopidogrel, ticagrelor had no statistical difference of major adverse cardiovascular events (RR 0.87; 95% CI 0.52-1.45; P =.58), all cause death (RR 0.90, 95% CI 0.62-1.32; P =.60), cardiovascular death (RR 0.90, 95% CI 0.47-1.72; P =.74), myocardial infarction (RR 0.91, 95% CI 0.52-1.58; P =.73), and stroke (RR 0.87, 95% CI 0.48-1.57; P =.64). Despite ticagrelor did not increase the incidence of fatal bleeding (RR 2.49, 95% CI 0.79-7.87; P = 0.12), the risks of all bleeding (RR 1.71, 95% CI 1.36-2.16; P <.00001), major bleeding (RR 1.51, 95% CI 1.12-2.04; P =.007), non-coronary artery bypass grafting major bleeding (RR 1.83, 95% CI 1.23-2.71; P =.003), and minor bleeding (RR 1.92, 95% CI 1.40-2.64; P <.0001) were significantly higher.

Conclusions: Although there was no significant difference in the incidence of fatal bleed-ing, ticagrelor displayed similar efficacy and dramatically increased the risk of other bleeding events.

Background: In patients with essential hypertension, fragmented QRS has been associated with many remodeling components that might lead to adverse cardiovascular effects. This study aimed to evaluate the relationship between fragmented QRS and adverse events and its potential long-term prognostic value.

Methods: The patients with essential hypertension were divided into two groups accord-
ing to the presence of fragmented QRS: fragmented QRS (+) and fragmented QRS (−). During long-term follow-up, the relationship of fragmented QRS to coronary artery dis-ease, congestive heart failure, stroke, cardiovascular death, all-cause death, and major adverse cardiovascular and cerebrovascular events was evaluated.

Results: The study group included 542 patients with essential hypertension. Fragmented QRS on ECG was observed in 224 (41.3%) patients. Considering the incidence rates at the
end of 5.6 ± 1.3 years’ follow-up, the total incidence rate of major adverse cardiovascular and cerebrovascular events (P <.001), coronary artery disease (P <.001), and congestive heart failure (P <.001) were higher in patients with fragmented QRS. No significant difference was observed between the two groups in terms of stroke (P =.734), cardiovascular death (P = 1), and all-cause death (P =.574). As a result of multiple cox regression analysis, fragmented QRS (P =.005) was identified as an independent predictor for major adverse cardiovascular and cerebrovascular events development.

Conclusion: In patients with hypertension, the presence of fragmented QRS was found as an independent predictor for major adverse cardiovascular and cerebrovascular events development.

Background: Previous cohort studies focused on relative risk stratification among patients diagnosed with vasospastic angina, and it is unknown how much vasospasm accounts for the cause of out-of-hospital cardiac arrest, and whether prognosis differs.

Methods: From a registry data collected from 65 hospitals in Korea, 863 subjects who survived hospital cardiac arrest were evaluated. The patients with insignificant coro-nary lesion, vasospasm, and obstructive lesion were each grouped as group I, group II, and group III, respectively. The primary and secondary outcomes were survival to hospital discharge and good neurological function at discharge defined as cerebral performance index 1.

Results: At hospital discharge, 529 subjects (61.3%) survived. There was no significant difference in survival according to coronary angiographic findings (P =.133 and P =.357, group II and group III compared to group I), but the neurological outcome was significantly better in groups II and III (P =.046 and P =.022, groups II and III compared to group I). Two multivariate models were evaluated to adjust traditional risk factors and cardiac biomarkers. The presence of coronary artery vasospasm did not affect survival to hospital discharge (P = 0.060 and P =.162 for both models), but neurological function was significantly better (OR: 1.965, 95% CI: 1.048-3.684, P =.035, and OR: 1.706, 95% CI: 1.012-2.878, P =.045 for vasospasm, models I and II, respectively).

Conclusions: Coronary vasospasm does not show better survival to hospital discharge, but shows better neurological outcomes. Aggressive coronary angiography and intensive medical treatment for adequate control of vasospasm should be emphasized to prevent and manage fatal events.

Background: Hereditary cardiac arrhythmias result from mutations in various genes encoding ion channels. One major channelopathy is long QT syndrome, which has excel-lent genetic and clinical heterogeneity. Arrhythmogenic right ventricular cardiomyopathy, another hereditary arrhythmia type, also shows high genetic heterogeneity and variable expressivity. Next-generation sequencing is an effective tool to reveal the dis-ease’s underlying genetic etiology.

Methods: In this study, we performed clinical exome sequencing or gene panel including cardiac arrhythmia and cardiomyopathy-associated genes by next-generation sequencing in 13 unrelated patients.

Results: Five pathogenic or likely pathogenic mutations, including three novel mutations, were found in the total cases.

Conclusion: This research shows a strong genetic heterogeneity in the disease. In addition, the study revealed that patients with QT interval prolongation on electrocardiogram might also have mutations in genes that are not associated with long QT syndrome, such as MYLK2 and DSG2. Therefore, our data helped expand the molecular scope of long QT syndrome. It is necessary to study with a broad perspective to elucidate the underly-ing molecular etiology in patients with hereditary cardiac arrhythmias.

Background: Bicuspid aortic valve is a congenital cardiac malformation that affects not only the valve and ascending aorta but also the abdominal aorta and large central arteries like carotid arteries by damaging the elasticity of the vessel resulting in increased stiffness and reduced distensibility. Deterioration of aortic compliance disturbs functions of the left ventricle and triggers atherosclerosis determined with carotid intima-media thickness. The aim of this study was to assess the effect of the bicuspid aortic valve on the elastic properties of these parts of the arterial system in children.

Methods: Thirty-four children with bicuspid aortic valves with normal valvular functions or mild valvular dysfunction and a control group of 34 individuals with tricuspid aortic valves were included in the study. Echocardiographic measurements of the left ventri-cle, ascending aorta, and ultrasonographic measurements of the abdominal aorta and carotid arteries were performed, and elasticity indexes were calculated.

Results: The bicuspid aortic valve group had higher stiffness and lower distensibility in ascending aorta, abdominal aorta, and carotid arteries with higher carotid intima-media thickness values than the tricuspid aortic valve group. Aortic valvular z scores and ascending aorta and abdominal aorta stiffness were higher in patients with bicus-pid aortic valves irrespective of valvular functions than in controls. Valvular dysfunction affected stiffness in carotid arteries. Dilatation of ascending aorta increased stiffness in the abdominal aorta. Distensibility was lower in ascending aorta and left carotid artery, with increased carotid intima-media thickness independent from ascending aorta dilatation. Stiffness of abdominal aorta revealed a positive correlation with the stiffness of
the ascending aorta and the carotid arteries (P <.05, for all).

Conclusions: Elasticity indexes of children with bicuspid aortic valves were impaired in ascending aorta, abdominal aorta, and carotid arteries with an increase in carotid intima-media thickness.

Background: To assess whether hypoxia, as can be found in obstructive sleep apnea syndrome, is causally associated with the development of heart failure through a direct effect on calcium leakage from the sarcoplasmic reticulum.

Methods: The impact of hypoxia on sarcoplasmic reticulum calcium leakage and expression of RyR2 (ryanodine receptor2) and SERC2a (sarcoplasmic reticulum Ca2+ATPase 2a) was investigated together with the outcomes of JTV-519 and S107 treatment. HL-1 cardiomyocytes were cultured for 7 days on gas-permeable cultureware under control (12% O2) or hypoxic (1% O2) conditions with or without JTV-519 or S107. SRCL was assessed using a Fluo-5N probe. Gene and protein expression was analyzed using qPCR and western blotting.

Results: Hypoxic exposure increased sarcoplasmic reticulum calcium leakage by 39% and reduced RyR2 gene expression by 52%. No effect on RyR2 protein expression was observed. Treatment with 1µM JTV-519 reduced sarcoplasmic reticulum calcium leakage by 52% and 35% under control and hypoxic conditions, respectively. Administration of 1 µM JTV-519 increased RyR2 gene expression by 89% in control conditions. No effect on SRCL, RyR2, or SERC2a gene, or protein expression was observed with S107 treatment.

Conclusion: Hypoxia increased sarcoplasmic reticulum calcium leakage which was ameliorated by JTV-519 treatment independently of gene or protein expression. JTV-519 rep-resents a possible treatment for obstructive sleep apnea-associated HF.

Background: High-power short-duration radiofrequency ablation has improved lesion durability in pulmonary vein isolation. In this study, we investigate long-term clinical out-comes of high-power short-duration pulmonary vein isolation and posterior wall debulking as an initial treatment modality in all corner atrial fibrillation patients.

Methods: This is a single-center, retrospective, observational study including all patients who have undergone high-power short-duration pulmonary vein and posterior wall debulking, regardless of atrial fibrillation type and/or duration. High-power short-duration power delivery protocol was defined as 45 W at all ablation sites. Clinical and electrocardiographic follow-up were performed in all patients.

Results: One hundred forty-two patients were enrolled in this study. Paroxysmal atrial fibrillation was present in 88 (62%) of patients. The mean follow-up of this study was
36.9 months ± 12.2 months. During the follow-up period, 10 patients (11.4%) with a diagnosis of paroxysmal atrial fibrillation had recurrence, while recurrence in patients with persistent and long-standing persistent atrial fibrillation was slightly higher (15 patients (28.1%) and 5 patients (50%), respectively). No major life-threatening complications occurred.

Conclusion: This study has demonstrated excellent arrhythmia-free outcomes in unselected, real world atrial fibrillation patients undergoing high-power short-duration pulmonary vein and debulking posterior wall isolations, however larger randomized trials are warranted.