Clinical and Genetic Features of Korean Inherited Arrhythmia Probands

Background and Objectives@#Inherited arrhythmia (IA) is a more common cause of sudden cardiac death in Asian population, but little is known about the genetic background of Asian IA probands. We aimed to investigate the clinical characteristics and analyze the genetic underpinnings of IA in a Korean cohort. @*Methods@#This study was conducted in a multicenter cohort of the Korean IA Registry from 2014 to 2017. Genetic testing was performed using a next-generation sequencing panel including 174 causative genes of cardiovascular disease. @*Results@#Among the 265 IA probands, idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) was the most prevalent diseases (96 and 95 cases respectively), followed by long QT syndrome (LQTS, n=54). Two-hundred-sixteen probands underwent genetic testing, and 69 probands (31.9%) were detected with genetic variant, with yield of pathogenic or likely pathogenic variant as 6.4%. Left ventricular ejection fraction was significantly lower in genotype positive probands (54.7±11.3 vs. 59.3±9.2%, p=0.005). IVF probands showed highest yield of positive genotype (54.0%), followed by LQTS (23.8%), and BrS (19.5%). @*Conclusions@#There were significant differences in clinical characteristics and genetic yields among BrS, LQTS, and IVF. Genetic testing did not provide better yield for BrS and LQTS. On the other hand, in IVF, genetic testing using multiple gene panel might enable the molecular diagnosis of concealed genotype, which may alter future clinical diagnosis and management strategies.

Electrical Remodeling of Left Atrium Is a Better Predictor for Recurrence Than Structural Remodeling in Atrial Fibrillation Patients Undergoing Radiofrequency Catheter Ablation

Background and Objectives@#Recurrence rates after radiofrequency catheter ablation (RFCA) in atrial fibrillation (AF) patients are not low especially in non-paroxysmal AF. The diameter of left atrium (LA) has been widely used to predict the recurrence after RFCA for decades. However, LA diameter represents structural remodeling of LA and does not reflect electrical remodeling. We aimed to determine the predictive value of electrical remodeling of LA which is represented by the amount of low voltage zone (LVZ). @*Methods@#We performed a retrospective cohort analysis of AF patients who underwent de novo RFCA in a single-center. @*Results@#A total of 3,120 AF patients with de novo RFCA were analyzed. Among these patients, 537 patients underwent an electroanatomic mapping with bipolar voltage measurement of LA.The diameter of LA and flow velocity of LA appendage (LAA) differed significantly according to quartile group of LVZ area and percentage: patients with high LVZ had large LA diameter and low LAA flow velocity (p<0.001). Freedom from late recurrence (LR) was significantly lower in patients with high LVZ area and percentage (p<0.001). The diameter and surface area of LA had area under curve (AUC) of 0.592 and 0.593, respectively (p=0.002 for both). The predictive value of LVZ area (AUC, 0.676) and percentage (AUC, 0.671) were both superior compared with LA diameter (p=0.011 and 0.027 for each comparison). @*Conclusions@#In conclusion, LVZ can predict freedom from LR after RFCA in AF patients. Predictive value was higher in parameters reflecting electrical rather than structural remodeling of LA.

Inherited arrhythmia syndrome predisposing to sudden cardiac death

Inherited arrhythmia (IA) is one of the main causes of sudden cardiac death (SCD) in young people, and is reported to be a more prevalent cause of SCD in Asia than in Western countries. IAs are a group of genetic disorders caused by mutations in genes encoding cardiac ion channels, leading to electrophysiological characteristics that often occur in the absence of structural abnormalities. Channelopathies, such as long QT syndrome and Brugada syndrome, carry a potential risk of life-threatening ventricular tachyarrhythmias that predispose to SCD, although early prediction and prevention of the risk remain challenging. Recent advances in genetic testing have facilitated risk stratification as well as a precise diagnosis for IA, despite ongoing debates about the implications. Herein, we provide epidemiological data, a pathophysiological overview, and the current clinical approach to IAs related to SCD. In addition, we review the general issues arising from genetic testing for IAs.

The 10-Year Trend of Out-of-hospital Cardiac Arrests: a Korean Nationwide Population-Based Study

Background and Objectives@#It is crucial to understand the exact public health burden of out-of-hospital cardiac arrest (OHCA) cases; this is presently unknown since sufficient episodes are not reported in registry studies. We aimed to evaluate the epidemiologic features and outcomes of non-traumatic OHCA. @*Methods@#During January 2008 to December 2017, we enrolled 387,665 patients who had been assigned a code for sudden cardiac arrest or had undergone cardiopulmonary resuscitation in the emergency room using the Korean National Health Insurance Service database. Those whose arrest was of non-cardiac origin were excluded. @*Results@#The incidence of OHCA per 100,000 patients increased steadily from 48.2 in 2008 to, 53.8 in 2011, 60.1 in 2014, and 66.7 in 2017, with a 1-year survival rate of 8.2%. Age and sex-adjusted mortality rates showed a decreasing trend. The hazard ratio was 1.0015 in 2009, 0.9865 in 2012, 0.9769 in 2015, and 0.9629 in 2017 (p for trend <0.0001), with coronary artery disease-related OHCA accounting for 59.8% of the total. Subgroups with coronary artery disease-related OHCA were more likely to be older and have a higher prevalence of all related comorbidities, excluding malignancy, than those with non-coronary artery disease-related OHCA. @*Conclusions@#This nationwide population-based study showed that the incidence of OHCA in Korea had increased during the last decade. The post OHCA 1-year mortality rate showed a poor outcome but improved gradually.

Impact of carotid atherosclerosis in CHA2DS2-VASc-based risk score on predicting ischemic stroke in patients with atrial fibrillation

Background/Aims@#Vascular disease is an established risk factor for stroke in patients with atrial fibrillation (AF), which is included in CHA2DS2-VASc score. However, the role of carotid atherosclerosis remains to be determined. @*Methods@#Three hundred-ten patients with AF who underwent carotid sonography were enrolled. @*Results@#During a median follow-up of 31 months, 18 events (5.8%) of stroke were identified. Patients with stroke had higher carotid intima-media thickness (CIMT) (1.16 ± 0.33 mm vs. 0.98 ± 0.25 mm, p = 0.017). CIMT was significantly increased according to the CHA2DS2-VASc score (p < 0.001) and it was correlated with left ventricular mass index and early diastolic mitral annular velocity (e’), a ratio of early transmitral flow velocity to e’ (E/e’) and pulmonary artery systolic pressure (all p < 0.05). Cox regression using multivariate models showed that carotid plaque was associated with the risk of stroke (hazard ratio, 3.748; 95% confidence interval [CI], 1.107 to 12.688; p = 0.034). C-statistics increased from 0.648 (95% CI, 0.538 to 0.757) to 0.716 (95% CI, 0.628 to 0.804) in the CHA2DS2-VASc score model after the addition of CIMT and carotid plaque as a vascular component (p = 0.013). @*Conclusions@#Increased CIMT and presence of carotid plaque are associated with a high risk of ischemic stroke, and CIMT is related to myocardial remodeling and diastolic dysfunction, suggesting that carotid atherosclerosis can improve risk prediction of stroke in patients with AF, when included under vascular disease in the CHA2DS2-VASc scoring system.

Inherited arrhythmia syndrome predisposing to sudden cardiac death

Inherited arrhythmia (IA) is one of the main causes of sudden cardiac death (SCD) in young people, and is reported to be a more prevalent cause of SCD in Asia than in Western countries. IAs are a group of genetic disorders caused by mutations in genes encoding cardiac ion channels, leading to electrophysiological characteristics that often occur in the absence of structural abnormalities. Channelopathies, such as long QT syndrome and Brugada syndrome, carry a potential risk of life-threatening ventricular tachyarrhythmias that predispose to SCD, although early prediction and prevention of the risk remain challenging. Recent advances in genetic testing have facilitated risk stratification as well as a precise diagnosis for IA, despite ongoing debates about the implications. Herein, we provide epidemiological data, a pathophysiological overview, and the current clinical approach to IAs related to SCD. In addition, we review the general issues arising from genetic testing for IAs.

The 10-Year Trend of Out-of-hospital Cardiac Arrests: a Korean Nationwide Population-Based Study

Background and Objectives@#It is crucial to understand the exact public health burden of out-of-hospital cardiac arrest (OHCA) cases; this is presently unknown since sufficient episodes are not reported in registry studies. We aimed to evaluate the epidemiologic features and outcomes of non-traumatic OHCA. @*Methods@#During January 2008 to December 2017, we enrolled 387,665 patients who had been assigned a code for sudden cardiac arrest or had undergone cardiopulmonary resuscitation in the emergency room using the Korean National Health Insurance Service database. Those whose arrest was of non-cardiac origin were excluded. @*Results@#The incidence of OHCA per 100,000 patients increased steadily from 48.2 in 2008 to, 53.8 in 2011, 60.1 in 2014, and 66.7 in 2017, with a 1-year survival rate of 8.2%. Age and sex-adjusted mortality rates showed a decreasing trend. The hazard ratio was 1.0015 in 2009, 0.9865 in 2012, 0.9769 in 2015, and 0.9629 in 2017 (p for trend <0.0001), with coronary artery disease-related OHCA accounting for 59.8% of the total. Subgroups with coronary artery disease-related OHCA were more likely to be older and have a higher prevalence of all related comorbidities, excluding malignancy, than those with non-coronary artery disease-related OHCA. @*Conclusions@#This nationwide population-based study showed that the incidence of OHCA in Korea had increased during the last decade. The post OHCA 1-year mortality rate showed a poor outcome but improved gradually.

Microbiota Influences Vaccine and Mucosal Adjuvant Efficacy

A symbiotic relationship between humans and the microbiota is critical for the maintenance of our health, including development of the immune system, enhancement of the epithelial barrier, and acquisition of nutrients. Recent research has shown that the microbiota impacts immune cell development and differentiation. These findings suggest that the microbiota may also influence adjuvant and vaccine efficacy. Indeed, several factors such as malnutrition and poor sanitation, which affect gut microbiota composition, impair the efficacy of vaccines. Although there is little evidence that microbiota alters vaccine efficacy, further understanding of human immune system-microbiota interactions may lead to the effective development of adjuvants and vaccines for the treatment of diseases.

Staged versus One-Time Percutaneous Coronary Intervention Strategy for Multivessel Non-ST Segment Elevation Acute Coronary Syndrome

No abstract available.

Does a Negative Ergonovine Provocation Test Truly Predict Freedom from Variant Angina?

Ergonovine provocation test is known to be very sensitive for diagnosing variant angina. The patient described in this study initially presented with atypical chest pain and underwent coronary angiography and ergonovine provocation tests, which were negative. The patient was subsequently prescribed a proton pump inhibitor and prokinetics for pain relief, but then presented with acute myocardial infarction and cardiogenic shock due to coronary artery vasospasm 5 years later. This case suggests that ergonovine provocation test generates false negative results, which can lead to unwanted outcomes. Even with a negative ergonovine provocation test, prescription of calcium channel blockers or nitrates should be considered in patients with a clinical history suggestive of variant angina.

Acute Pulmonary Embolism due to Thrombus-in-Transit in the Right Atrium During Bipolar Endoprosthesis of the Hip / 대한내과학회지

Venous thromboembolism is a relatively common condition in inhospital patients, but it may also manifest as a lethal disease. However, the diagnosis is not suspected clinically in the vast majority of cases. Most hospitalized patients are at risk of venous thromboembolism, but the risk can be reduced significantly by appropriate prophylaxis. We herein report a case of a huge right atrial thrombus that presented as sudden cardiogenic shock during bipolar endoprosthesis of the hip due to a femoral neck fracture. Although the patient was elderly and immobile for 3 days before hip surgery, she did not receive prophylaxis for venous thromboembolism. More attention should be paid to venous thromboembolism prophylaxis in high-risk patients.

Primary Malignant Pericardial Mesothelioma Presenting as Acute Pericarditis

We report on a 21-year-old man with fever, dyspnea, and pleuritic chest pain. An electrocardiography showed ST elevation in multiple lead and thoracic echocardiography revealed moderate pericardial effusion. He was initially diagnosed with acute pericarditis, and treated with nonsteroidal anti-inflammatory drugs and colchicines with clinical and laboratory improvement. After 1 month of medication, his symptoms recurred. An echocardiography showed constrictive physiology and the patient was treated with steroid on the top of current medication. The patient had been well for 7 months until dyspnea and edema developed, when an echocardiography showed marked increased pericardial thickness and constriction. Pericardial biopsy was performed and primary malignant pericardial mesothelioma was diagnosed. Malignancy should be considered in the differential diagnosis of recurrent pericarditis.

Primary Malignant Pericardial Mesothelioma Presenting as Acute Pericarditis

We report on a 21-year-old man with fever, dyspnea, and pleuritic chest pain. An electrocardiography showed ST elevation in multiple lead and thoracic echocardiography revealed moderate pericardial effusion. He was initially diagnosed with acute pericarditis, and treated with nonsteroidal anti-inflammatory drugs and colchicines with clinical and laboratory improvement. After 1 month of medication, his symptoms recurred. An echocardiography showed constrictive physiology and the patient was treated with steroid on the top of current medication. The patient had been well for 7 months until dyspnea and edema developed, when an echocardiography showed marked increased pericardial thickness and constriction. Pericardial biopsy was performed and primary malignant pericardial mesothelioma was diagnosed. Malignancy should be considered in the differential diagnosis of recurrent pericarditis.

Differential Expressions of Synaptogenic Markers between Primary Cultured Cortical and Hippocampal Neurons

Primary dissociated neuronal cultures are widely used research tools to investigate of pathological mechanisms and to treat various central and peripheral nervous system problems including trauma and degenerative neuronal diseases. We introduced a protocol that utilizes hippocampal and cortical neurons from embryonic day 17 or 18 mice. We applied appropriate markers (GAP-43 and synaptophysin) to investigate whether neurite outgrowth and synaptogenesis can be distinguished at a particular period of time. GAP-43 was found along the neural processes in a typical granular pattern, and its expression increased proportionally as neurites lengthened during the early in vitro period. Unlike GAP-43, granular immunoreactive patterns of synaptophysin along the neurites were clearly found from day 2 in vitro with relatively high immunoreactive levels. Expression of synaptic markers from cortical neurons reached peak level earlier than that of hippocampal neurons, although neurite outgrowths of hippocampal neurons were faster than those of cortical neurons. The amount of peak synaptic markers expressed was also higher in cortical neurons than that in hippocampal neurons. These results strongly suggest the usefulness of primary cultured neurons from mice embryos for synaptic function and plasticity studies, because of their clear and typical patterns of morphology that establish synapses. Results from this study also suggest the proper amount of time in vitro according to neuronal types (cortical or hippocampal) when utilized in experiments related with synaptogenesis or synaptic activities.