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Background: Exosomes are membrane vesicles that are actively secreted in response to microenvironmental stimuli. In this study, we quantified the amount of exosomes in patients with significant coronary artery disease (CAD) and evaluated its relationship with myocardial perfusion imaging (MPI) results. Methods: Patients who underwent both MPI and coronary angiography were recruited. Plasma was collected during angiography, and exosomes were extracted via the precipitation method. The summed stress scores (SSS), summed difference scores, and ventricular functional parameters were calculated from the MPI and compared with the amounts of exosomes and extracted miRNAs. Results: In total, 115 patients were enrolled (males: 78 %; mean age: 66.6 ± 10.6 years). Those with abnormal SSS according to the MPI had significantly fewer exosomes (p = 0.032). After multivariate analysis, the SSS remained significantly related to the amount of exosomes (p = 0.035). In forty randomly selected samples, miRNA-432–5p and miRNA-382–3p were upregulated in patients with abnormal SSS. Conclusion: Patients with compromised poststress myocardial perfusion on MPI tended to have fewer exosomes in association with CAD-related miRNAs. This is the first study to clarify the fundamental and pathophysiological causes of CAD using radiographic examinations.

Background As the burden and distribution of calcification within chronic total occlusion (CTO) lesions can be diverse, its effect on CTO recanalization using multiple devices and techniques is debatable. This study investigated the role of calcification in wiring-based intraplaque tracking techniques for CTO recanalization.Methods A modified J-CTO score without counting calcification was used to analyze the procedures of 458 consecutive patients who underwent CTO interventions. Failed guidewire crossing and intraplaque tracking were considered procedural failures. Recanalization time details were analyzed for successful procedures.Results In patients with calcified CTO, the rate of procedural success only significantly declined to be lower than that of noncalcified CTO when the modified J-CTO score was ≥3 (77% vs. 94%, p = 0.008). In 422 patients with successful procedures, the presence of calcification was irrelevant to guidewire crossing time, but was accompanied with longer time from guidewire cross to final angiogram when the modified J-CTO score was 1–2 (53 ± 35 vs. 35 ± 17 [noncalcified] min, p 60 min (OR = 4.8, 95% CI = 2.2–10.2) in successfully recanalized lesions with modified J-CTO score 1–2.Conclusions Using intraplaque guidewire tracking, calcification was unfavorable for very difficult CTO lesions, and caused prolongation of angioplasty time for lesions with moderate complexity. This suggested that the role of calcification in the J-CTO score could be altered when different recanalization techniques were applied for CTO interventions.

Objective: In patients with atrial fibrillation (AF) and end-stage renal disease (ESRD), oral anticoagulants are contraindicated, and left atrial appendage occlusion (LAAO) is an alternative treatment. However, the efficacy of thromboembolic prevention using LAAO in these patients has rarely been reported in Asian populations. To our knowledge, this is the first long-term LAAO study in patients with AF undergoing dialysis in Asia. Methods: In this study, 310 patients (179 men) with a mean age of 71.3 ± 9.6 years and mean CHA2DS2-VASc 4.2 ± 1.8 were consecutively enrolled at multiple centers in Taiwan. The outcomes of 29 patients with AF and ESRD undergoing dialysis who underwent LAAO were compared to those without ESRD. The primary composite outcomes were stroke, systemic embolization, or death. Results: No difference in mean CHADS-VASc score was noted between patients with versus without ESRD (4.1 ± 1.8 vs. 4.6 ± 1.9, p = 0.453). After a mean follow-up of 38 ± 16 months, the composite endpoint was significantly higher in patients with ESRD (hazard ratio, 5.12 [1.4–18.6]; p = 0.013) than in those without ESRD after LAAO therapy. Mortality was also higher in patients with ESRD (hazard ratio, 6.6 [1.1–39.7]; p = 0.038). The stroke rate was numerically higher in patients with versus without ESRD, but the difference was not statistically significant (hazard ratio, 3.2 [0.6–17.7]; p = 0.183). Additionally, ESRD was associated with device-related thrombosis (odds ratio, 6.15; p = 0.047). Conclusion: Long-term outcomes of LAAO therapy may be less favorable in patients with AF undergoing dialysis, possibly because of the poor condition of patients with ESRD.

Background/Purpose: School-based cardiac screening is useful for identifying children and adolescents with a high risk of sudden cardiac death. However, because of challenges associated with cost, distance, and human resources, cardiac screening is not widely implemented, especially in rural areas with limited medical resources. This study aims to establish a cloud-based system suitable for mass cardiac screening of schoolchildren in rural areas with limited medical resources. Methods: Students from three schools were included. They or their guardians completed a simple questionnaire, administered in paper or electronic form. Heart sounds were recorded using an electronic stethoscope. Twelve-lead electrocardiograms (ECGs) were recorded and digitalized. The signals were transmitted through Bluetooth to a tablet computer and then uploaded to a cloud server over Wi-Fi. Crowdsourced pediatric cardiologists reviewed those data from a web-based platform and provided remote consultation. In cases in which abnormal heart sounds or ECGs were noted, the students were referred to the hospital for further evaluation. Results: A total of 1004 students were enrolled in this study. Of the 138 students referred, 62 were diagnosed as having an abnormal heart condition and most had previously been undiagnosed. The interrater agreeability was high. Conclusion: An innovative strategy combining a cloud-based cardiac screening system with remote consultation by crowdsourced experts was established. This system allows pediatric cardiologists to provide consultation and make reliable diagnoses. Combined with crowdsourcing, the system constitutes a viable approach for mass cardiac screening in children and adolescents living in rural areas with insufficient medical resources.

Background: Demographics of pulmonary hypertension (PH) has changed a lot over the past forty years. Several recent registries noted an increase in mean age of PH but only a few of them investigated the characteristics of elderly patients. Thus, we aimed to analyze the characteristics of PH in such a population in this study. Methods: This multicenter study enrolled patients diagnosed with PH in group 1, 3, 4, and 5 consecutively from January 1, 2019 to December 31, 2020. A total of 490 patients was included, and patients were divided into three groups by age (≤45 years, 45–65 years, and >65 years). Results: The mean age of PH patients diagnosed with PH was 55.3 ± 16.3 years of age. There was higher proportion of elderly patients classified as group 3 PH (≤45: 1.3, 45–65: 4.5, >65: 8.1 %; p = 0.0206) and group 4 PH (≤45: 8.4, 45–65: 14.5, >65: 31.6 %; p 65, mean difference, 77.8 m [95% confidence interval (CI), 2.1–153.6 m]), lower mean pulmonary arterial pressure (mPAP) (≤45 vs. >65, mean difference, 10.8 mmHg [95% CI, 6.37–15.2 mmHg]), and higher pulmonary arterial wedge pressure (PAWP) (≤45 vs. 45–65, mean difference, −2.1 mmHg [95% CI, −3.9 to −0.3 mmHg]) compared to young patients. Elderly patients had a poorer exercise capacity despite lower mPAP level compared to young population, but they received combination therapy less frequently compared to young patients (triple therapy in group 1 PH, ≤45: 16.7, 45–65: 11.3, >65: 3.8 %; p = 0.0005). Age older than 65 years was an independent predictor of high mortality for PH patients. Conclusions: Elderly PH patients possess unique hemodynamic profiles and epidemiologic patterns. They had higher PAWP, lower mPAP, and received combination therapy less frequently. Moreover, ageing is a predictor of high mortality for PH patients. Exercise capacity-hemodynamics mismatch and inadequate treatment are noteworthy in the approach of elderly population with PH.

Introduction: Social participation activities have a close association with health aging. However, the clinical significance of numbers of social participation activities and its cutoff value has not been defined. Methods: We recruited 516 people aged ≥55 years. Twelve social participation behaviors modified according to Taiwanese culture were investigated, and the adequacy of cutoff number was determined by the area under the receiver operating characteristic curve (AUC) according to the results of cluster analysis of individual activities and scores of the Brief Symptom Rating Scale-5 (BSRS-5) and the Chinese Happiness Inventory (CHI). Demographic, BSRS-5 and CHI data were then compared according to the candidate cutoff numbers. Results: The distribution of the numbers of social activities suggested that the highest partition of numbers of social activities was 3 in women and 4 in men. The AUC regarding the cluster of activity types was 0.917, with the highest Youden's J value located between 3 and 4. The AUC regarding the cluster of activity types and scores of the BSRS-5 and the CHI was 0.929, with similar cutoffs. If 3 and 4 were used as cutoffs, the between-group differences of both the CHI and the BSRS-5 were significant. More types of social activities had a different engaging frequency with the 3 and 4 cutoffs. Conclusion: Our findings found an adequate cutoff with better differential power in the psychopathology and happiness of older people that provided a basis for application in intervention and policy formation.

Background Implantation of the left atrial appendage occluder (LAAO) has been proven to prevent stroke effectively in patients with atrial fibrillation who cannot tolerate anticoagulants. Incomplete endothelization of LAAO may cause device‐related thrombus, and currently no good image modality exists to clearly see LAAO endothelialization. We aimed to use coronary optic coherence tomography (OCT) to visualize LAAO endothelialization. Methods and Results We enrolled 14 patients (72.8±9.4 years old) undergoing pulmonary vein isolation with a preexisting LAAO implanted more than 1 year ago (5 Watchman and 9 Amulet). After pulmonary vein isolation, we did OCT via steerable sheath and coronary guiding catheter to adjust OCT probe location and injected contrast medium to visualize the LAAO surface. In vitro testing was also performed to see the bare occluder. In vitro OCT showed the surface of the bare device as an interrupted granule pattern, which included the Watchman surface polytetrafluoroethylene membrane string, Amulet disc metal strut, and inner polytetrafluoroethylene membrane string. In the implanted Watchman, OCT showed endothelialization as a smooth surface layer with noninterrupted coarser granules. In the implanted Amulet, OCT showed endothelialization as thin (early) or thick (late) endothelialization layer covering struts with OCT shadows. Among patients with Watchman, 2 showed no, 2 early, and 1 complete endothelialization. Among patients with Amulet, 2 showed no, 3 early, and 4 late endothelialization. Conclusions We demonstrated the feasibility of OCT to visualize LAAO endothelization with high resolution. Further studies are needed to determine antithrombotic regimens if incomplete endothelization is detected. A new OCT catheter may be designed specifically for LAAO.

Background Myocardial steatosis and fibrosis may play a role in the pathophysiology of heart failure with preserved ejection fraction. We therefore investigated the prognostic significance of epicardial fat (epicardial adipose tissue [EAT]) and myocardial diffuse fibrosis. Methods and Results Myocardial fibrosis, estimated as extracellular volume (ECV), and EAT were measured using cardiac magnetic resonance imaging in 163 subjects with heart failure with preserved ejection fraction. We also evaluated cardiac structure and diastolic and systolic function by echocardiography and cardiac magnetic resonance imaging. After 24 months' follow‐up, 39 (24%) subjects had experienced cardiovascular events, including hospitalization for heart failure, acute coronary syndrome, and cardiovascular death. Median EAT and mean ECV were significantly higher in subjects with cardiovascular events than survivors (EAT, 35 [25–45] versus 31 [21–38], P=0.006 and ECV, 28.9±3.16% versus 27.2±3.56%, P=0.04). Subjects with high EAT (≥42 g) had increased risk of cardiovascular events (hazard ratio [HR], 2.528 [95% CI, 1.704–4.981]; P=0.032). High ECV (>29%) was also significantly associated with poorer outcomes (HR, 1.647 [95% CI, 1.263–2.548]; P=0.013). With respect to secondary end points, high EAT and high ECV were associated with increased risk of the incident acute coronary syndrome (HR, 1.982 [95% CI, 1.008–4.123]; P=0.049) and hospitalization for heart failure (HR, 1.789 [95% CI, 1.102–6.987]; P=0.033), respectively. Conclusions Our study suggested that increased epicardial fat and ECV detected by cardiac magnetic resonance imaging have an impact on cardiovascular prognosis, in particular acute coronary syndrome and hospitalization for heart failure, respectively.

Abstract Background Ventricular premature complex (VPC) is a common arrhythmia in clinical practice. VPC could trigger ventricular tachycardia/fibrillation or VPC-induced cardiomyopathy in susceptible patients. Existing screening methods require prolonged monitoring and are limited by cost and low yield when the frequency of VPC is low. Twelve-lead electrocardiogram (ECG) is low cost and widely used. We aimed to identify patients with VPC during normal sinus rhythm (NSR) using artificial intelligence (AI) and machine learning-based ECG reading. Methods We developed AI-enabled ECG algorithm using a convolutional neural network (CNN) to detect the ECG signature of VPC presented during NSR using standard 12-lead ECGs. A total of 2515 ECG records from 398 patients with VPC were collected. Among them, only ECG records of NSR without VPC (1617 ECG records) were parsed. Results A total of 753 normal ECG records from 387 patients under NSR were used for comparison. Both image and time-series datasets were parsed for the training process by the CNN models. The computer architectures were optimized to select the best model for the training process. Both the single-input image model (InceptionV3, accuracy: 0.895, 95% confidence interval [CI] 0.683–0.937) and multi-input time-series model (ResNet50V2, accuracy: 0.880, 95% CI 0.646–0.943) yielded satisfactory results for VPC prediction, both of which were better than the single-input time-series model (ResNet50V2, accuracy: 0.840, 95% CI 0.629–0.952). Conclusions AI-enabled ECG acquired during NSR permits rapid identification at point of care of individuals with VPC and has the potential to predict VPC episodes automatically rather than traditional long-time monitoring.

Background: The purpose of this study was to investigate the psychopathology and level of happiness and their association with the demographic data of the older population in long-term care situations in Taiwan. Methods: The study enrolled 500 participants who were the elderly in long-term care situations and used the Brief Symptom Rating Scale (BSRS-5) and Chinese Happiness Inventory (CHI) to determine the psychopathology and level of happiness. Multiple linear regression analysis (using a stepwise method) and a two-step cluster analysis were performed to examine the data. Results: The results revealed mean scores for total CHI and total BSRS-5 of 16.08 and 2.34, respectively. Regular exercise habits, higher living expense and having a job were positively associated with happiness. Being older and living in an apartment/condominium were factors negatively associated with happiness. Living in an apartment/condominium was positively associated with a higher BSRS-5 score. Four clusters were grouped according to the variables that contributed the most: housing, exercise habits, living expense and working status. The cluster with no work, no exercise habits and lower living expense had the highest BSRS-5 score and the lowest CHI score. Conclusion: We concluded that the association between demographic data and happiness is stronger than the association between demographic data and psychopathology in a community sample in Taiwan. Those who have steady work, higher living expense and regular exercise habits have better happiness and less psychopathology.

Background/Purpose: Sport-specific adaptations of athlete's hearts are still under investigation. This study sought to 1) identify athlete groups with similar characteristics by clustering echocardiographic data; 2) externally validate the data-driven clusters with sport classifications of various dynamic or static loads to support the conventional hypothesis-driven approach in delineating the athlete's heart. Methods: Anthropometric, echocardiographic and electrocardiographic assessments were collected during the 2017 Summer Universiade in Taiwan. Besides standard echocardiography and strain measurements, ventricular-arterial coupling (VAC) was assessed by the ratio of effective arterial elastance (Ea) to left ventricular end-systolic elastance (Ees) as calculated by a modified single-beat algorithm. Results: We grouped 598 elite athletes (348 male, age 23 ± 2.5 years, across 24 disciplines) using Mitchell's classification. The hypothesis-driven analysis showed dynamic training-related adaptations in heart rate and morphology, including ventricular size, mass, and stroke volume. In comparison, the unsupervised approach found two clusters for each sex. Male athletes participating in high dynamic-load exercises had larger chambers, supranormal diastolic functions, depressed Ees, lower Ea and preserved optimal VAC implicating the resting status of a reservoir-rich pump, which affirmed sport-specific adaptation. The female athletes could be clustered with more noticeable functional alterations, such as depressed biventricular strain. However, the imbalanced number between clusters impeded the validation of load-related remodeling. Conclusion: Hierarchical clustering could analyze complicated multiparametric interactions among numerous echocardiography-derived phenotypes to discern the adaptive propensity of the athlete's heart. The endorsement or generation of hypotheses by a data-driven approach can be applied to various domains.

Background: Bioresorbable vascular scaffold (BVS) had been implanted to several kinds of complex coronary lesions in real-world practice. We tested if long-term outcomes of BVS for complex lesions would be worse than that for relatively simple lesions. Methods: We analyzed 457 patients (59 ± 12 years, 87% male) with 714 BVS implanted for their 529 lesions and median follow-up of 32.7 (26.8–39.3) months. Complex group (N = 284) was defined as those with BVS for acute coronary syndrome, chronic total occlusion, bifurcation/ostial lesions, instent restenosis/hybrid with metallic stents, diffuse lesions (overlapped by 2 BVS with each ≧ 18 mm), venous graft/left main lesions, or lesions after rotablation. We compared their outcomes with the remaining 173 patients as non-complex group. Results: The complex group had more chronic kidney disease (7% vs. 2%), multivessel disease (78% vs. 65%), use of intravascular imaging (40% vs. 23%), and more BVS (1.8 ± 0.9 vs. 1.1 ± 0.3) with longer total lengths (47 ± 22 vs. 29 ± 8 mm) implanted than non-complex group (all p 0.05) between the two groups. Multivariate Cox regression analyses showed BVS for ACC/AHA type C lesions was independently associated with higher risks of TLR (hazard ratio: 2.7, 95% CI = 1.1–6.6) and TLF (hazard ratio: 2.6, 95% CI = 1.1–6.3). Conclusion: Comparable outcomes were found between BVS for complex and non-complex lesion category. However, higher risks of TLR and TLF for type C lesions still suggested the prognostic impact of lesion complexity on long-term outcomes of BVS.

Background/Purpose: In patients with non-valvular atrial fibrillation (NVAF), the left atrial appendage occluder (LAAO) is an alternative treatment for stroke prevention. However, the long-term outcomes in Asia was generally unknown. Methods and Results: This was a retrospective longitudinal study and a total of 124 patients with contraindications to oral anticoagulants or stroke despite under anticoagulants had been enrolled since 2013. Primary efficacy was defined as any type of stroke/systemic embolization and adverse event as any procedure or anti-thrombotic related complications. Twelve patients were excluded due to thrombus in the LAA or oversize LAA. Watchman was successfully implanted in 55 patients (98%) and ACP/Amulet also 55 patients (98%). During follow-up, the ischemic stroke rate was 1.9 in the Watchman and 1.4 per 100 patient-year in the ACP/Amulet group. There were 2 Watchman patients experiencing intracranial hemorrhage. Device-related thrombus (DRT) was noted in 3 patients (2.7%).There was no patient with peri-device lead ≧5 mm. In those patients receiving only local anesthesia, the follow-up echocardiography showed no significant peri-device leak, malposition of LAAO and DRT. Conclusion: This long-term follow-up study shows that percutaneous closure of LAA is a safe and technically feasible procedure with satisfactory outcomes in Asia. The procedure success rate, efficacy and adverse event were similar to those reported in the Caucasian populations.

Background Atrial fibrillation (AF) is associated with increasing risk of thromboembolic or ischemic stroke. The CHA2DS2‐VASc score is a well‐established predictor of AF stroke. Patients with AF have an increased risk of stroke if they have diabetes. Use of sodium‐glucose cotransporter‐2 inhibitor (SGLT2i) has been shown to be associated with favorable cardiovascular outcomes in patients with diabetes. It was unknown whether use of SGLT2i decreased stroke risk in patients with AF who have diabetes. Methods and Results A total of 9116 patients with AF and diabetes from the National Taiwan University historical cohort were longitudinally followed up for 5 years (January 2016–December 2020). The risk of stroke related to SGLT2i use was evaluated by Cox model, adjusting CHA2DS2‐VASc score in the propensity score–matched population with 474 SGLT2i users and 3235 nonusers. Adverse thromboembolic end points during follow‐up were defined as ischemic stroke. The mean age was 73.2±10.5 years, and 61% of patients were men. There were no significant differences of baseline characteristics between users and nonusers of SGLT2i, including CHA2DS2‐VASc score in the propensity score–matched population. The stroke rate was 3.4% (95% CI, 2.8–4.2) patient‐years in SGLT2i users and 4.3% (95% CI, 4.0–4.6) in nonusers (P=0.021). SGLT2i users had a 20% reduction of stroke (hazard ratio, 0.80 [95% CI, 0.64–0.99]; P=0.043) after adjustment for the CHA2DS2‐VASc score. Conclusions Use of SGLT2i was associated with a lower stroke risk in patients with diabetes and AF, and it may be considered to escalate SGLT2i to the first‐line treatment in patients with diabetes and AF.

Abstract Melatonin exerts a wide range of effects among various tissues and organs. However, there is currently no study to investigate the genetic determinants of melatonin secretion. Here, we conducted a genome-wide association study (GWAS) for melatonin secretion using morning urine 6-hydroxymelatonin sulfate-to-creatinine ratio (UMCR). We initially enrolled 5000 participants from Taiwan Biobank in this study. After excluding individuals that did not have their urine collected in the morning, those who had history of neurological or psychiatric disorder, and those who failed to pass quality control, association of single nucleotide polymorphisms with log-transformed UMCR adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for estimated glomerular filtration rate (eGFR). A total of 2373 participants underwent the genome-wide analysis. Five candidate loci associated with log UMCR (P value ranging from 6.83 × 10−7 to 3.44 × 10−6) encompassing ZFHX3, GALNT15, GALNT13, LDLRAD3 and intergenic between SEPP1 and FLJ32255 were identified. Similar results were yielded with further adjustment for eGFR. Interestingly, the identified genes are associated with circadian behavior, neuronal differentiation, motor disorders, anxiety, and neurodegenerative diseases. We conducted the first GWAS for melatonin secretion and identified five candidate genetic loci associated with melatonin level. Replication and functional studies are needed in the future.

Background: End stage renal disease (ESRD) is an increasing worldwide epidemic disease. CHA2DS2-VASc score is a well-established predictor of cardiovascular outcome among atrial fibrillation (AF) patients. Objective: The aim of this study was to test whether CHA2DS2-VASc score is a good predictor for incident ESRD events. Methods: This is a retrospective cohort study (from January 2010 to December 2020) with median follow-up of 61.7 months. Clinical parameters and baseline characteristics were recorded. The endpoint was defined as ESRD with dialysis dependent. Results: The study cohort comprised 29,341 participants. Their median age was 71.0 years, 43.2% were male, 21.5% had diabetes mellitus, 46.1% had hypertension, and mean CHA2DS2-VASc score was 2.89. CHA2DS2-VASc score was incrementally associated with the risk of ESRD status during follow-up. Using the univariate Cox model, we found a 26% increase in ESRD risk with an increase of one point in the CHA2DS2-VASc score (HR 1.26 [1.23–1.29], P

Background: Diastolic dysfunction (DD) has shown to be a hallmark pathological intermediate in the development of heart failure with preserved ejection fraction (HFpEF). We aim to establish age- and sex-stratified normal reference values of diastolic indices and to explore racial-differences. Methods: We explored age- and sex-related structural/functional alterations from 6023 healthy ethnic Asians (47.1 ± 10.9 years, 61.3% men) according to 2016 American Society of Echocardiography (ASE) diastolic dysfunction (DD) criteria. Racial comparisons were made using data from London Life Sciences Prospective Population (LOLIPOP) study. Results: Age- and sex-based normative ranges (including mean, median, 10% and 90% lower and upper reference values) were extracted from our large healthy population. In fully adjusted models, advanced age was independently associated with cardiac structural remodeling and worsened diastolic parameters including larger indexed LA volume (LAVi), lower e’, higher E/e’, and higher TR velocity; all p

Since December 2019, the outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly around the world. The severity of COVID-19 ranges from asymptomatic carriers to severe acute respiratory distress syndrome (ARDS). Accumulating evidence has shown that COVID-19 may be associated with multiple organ complications including cardiac injury, viral myositis and neurological deficits. Numerous laboratory biomarkers including lymphocytes, platelets, lactate dehydrogenase and creatine kinase (CK) have been associated with the prognostic outcomes of patients with COVID-19. However, dynamic correlations between levels of biomarkers and clinical course have not been studied.Herein, we report a 74-year-old female patient with severe COVID-19 which progressed to ARDS requiring intubation and mechanical ventilation. The laboratory findings showed lymphopenia, hypogammaglobulinemia, and elevated inflammatory biomarkers and CK. She received intensive therapy with hydroxychloroquine, lopinavir/ritonavir, and azithromycin with limited effects. Immunomodulatory treatments with high dose intravenous immunoglobulin and baricitinib were prescribed with satisfactory biochemical, radiographic and clinical recovery. We found an interesting correlation between serum CK elevation and inflammatory biomarkers, which reflected clinical improvement. This case demonstrates that inflammatory biomarkers, cytokines, and CK level correlated with disease severity and treatment response, and combined use of intravenous immunoglobulin and baricitinib is a potential treatment in patients with severe COVID-19.

Type 2 diabetes is a major threat to human health in the 21st century. More than half a billion people may suffer from this pandemic disease in 2030, leading to a huge burden of cardiovascular complications. Recently, 2 novel antidiabetic agents, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, reduced cardiovascular complications in a number of randomized control trials. To integrate new information and to achieve a streamlined process for better patient care, a working group was appointed by the Taiwan Society of Cardiology to formulate a stepwise consensus pathway for these therapies to reduce cardiovascular events in patients with type 2 diabetes. This consensus pathway is complementary to clinical guidelines, acting as a reference to improve patient care.

Background: Among international cardiologists it is unclear whether equipoise exists regarding the benefit of diagnosing and managing obstructive sleep apnea (OSA) to improve atrial fibrillation (AF) outcomes and whether clinical practice and equipoise are linked. Methods: Between January 2019 and June 2020 we distributed a web-based 12-question survey regarding OSA and AF management to practicing cardiologists in 16 countries. Results: The United States, Japan, Sweden, and Turkey accounted for two-thirds of responses. 863 cardiologists responded; half were general cardiologists, a quarter electrophysiologists. Responses regarding treating OSA with CPAP to improve AF endpoints were mixed. 33% of respondents referred AF patients for OSA screening. OSA was diagnosed in 48% of referred patients and continuous positive airway pressure (CPAP) was prescribed for 59% of them. Nearly 70% of respondents believed randomized controlled trials (RCTs) of OSA treatment in AF patients were necessary and indicated willingness to contribute to such trials. Conclusions: There was no clinical equipoise among surveyed cardiologists; a majority expressed certainty that combined OSA and AF treatment is superior to AF treatment alone for improving AF outcomes. However, a minority of surveyed cardiologists referred AF patients for OSA testing, and while half of screened AF patients had OSA, CPAP was prescribed in little more than half of them, reflecting the view that better clinical trial evidence is needed to support this practice. Our results underscore the need for larger, multi-national prospective studies of OSA treatment and AF outcomes to inform more uniform society guideline recommendations.

Background: Data on the efficacy and safety of balloon pulmonary angioplasty (BPA) in Taiwanese patients with chronic thromboembolic pulmonary hypertension (CTEPH) are lacking. In this study, we evaluated the effects of BPA on clinical parameters including hemodynamics, echocardiography and functional status in patients with inoperable CTEPH in Taiwan. Methods: We retrospectively collected the clinical data of inoperable CTEPH patients who underwent ≥3 BPA sessions. Pulmonary hemodynamic parameters of right heart catheterization, echocardiography, 6-min walk distance and World Health Organization (WHO) functional class were collected and analyzed before and after BPA treatment. Results: A total of 59 BPA sessions were performed in 13 inoperable CTEPH patients. No periprocedural deaths or major complications requiring tracheal intubation with mechanical ventilation occurred. WHO functional class significantly improved in all 13 patients (P

Abstract Diabetes mellitus (DM) is a common comorbidity and risk factor for postoperative complications in head and neck (H&N) microsurgical reconstructions. Our study focused on the association between DM and individual complications regarding both surgical and medical aspects. A meta-analysis of English-language articles comparing a series of complications between DM and non-DM H&N free-flap recipients was performed by comprehensive meta-analysis (CMA). Twenty-seven articles presented 14,233 H&N free-flap reconstructions, and a subset of 2329 analyses including diabetic cases was included for final analysis. Total postoperative (RR = 1.194, p

Cryptogenic stroke comprises about one-quarter of ischemic strokes with high recurrence rate; however, studies specifically investigating the features and treatment of this stroke subtype are rare. The concept of ‘embolic stroke of undetermined source’ (ESUS) may facilitate the development of a standardized approach to diagnose cryptogenic stroke and improve clinical trials. Since recent large randomized control trials failed to demonstrate a reduction in stroke recurrence with anticoagulants, anti-platelet agents remain the first-line treatment for ESUS patients. Nevertheless, patients with high risk of stroke recurrence (e.g., those with repeated embolic infarcts despite aspirin treatment) require a more extensive survey of stroke etiology, including cardiac imaging and prolonged cardiac rhythm monitoring. Anticoagulant treatments may still benefit some subgroups of high-risk ESUS patients, such as those with multiple infarcts at different arterial territories without aortic atheroma, the elderly, or patients with high CHA2D2-VASc or HOVAC scores, atrial cardiopathy or patent foramen ovale. Several important ESUS clinical trials are ongoing, and the results are anticipated. With rapid progress in our understanding of ESUS pathophysiology, new subcategorizations of ESUS and assignment of optimal treatments for each ESUS subgroup are expected in the near future.

Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection with SARS-CoV may cause coronary plaque instability and lead to acute coronary syndrome (ACS). Management of ACS in patients with COVID-19 needs more consideration of the balance between clinical benefit and transmission risk of virus. This review provides recommendations of management strategies for ACS in patients with suspected or confirmed COVID-19 in Taiwan.

Background: Post-cardiac arrest care is critically important in bringing cardiac arrest patients to functional recovery after the detrimental event. More high quality studies are published and evidence is accumulated for the post-cardiac arrest care in the recent years. It is still a challenge for the clinicians to integrate these scientific data into the real clinical practice for such a complicated intensive care involving many different disciplines. Methods: With the cooperation of the experienced experts from all disciplines relevant to post-cardiac arrest care, the consensus of the scientific statement was generated and supported by three major scientific groups for emergency and critical care in post-cardiac arrest care. Results: High quality post-cardiac arrest care, including targeted temperature management, early evaluation of possible acute coronary event and intensive care for hemodynamic and respiratory care are inevitably needed to get full recovery for cardiac arrest. Management of these critical issues were reviewed and proposed in the consensus Conclusion: The goal of the statement is to provide help for the clinical physician to achieve better quality and evidence-based care in post-cardiac arrest period.

BackgroundLesion characteristics were shown to predict procedural success and outcomes in chronic total occlusion (CTO) recanalization. However, diverse techniques involved in these studies might cause potential heterogeneity.ObjectiveThe study aimed to test the impacts of lesion characteristics on CTO intervention with a pure antegrade wiring-based technique.Methods and ResultsWe studied consecutive 325 patients (64.5 ± 11.1 years, 285 men) with native CTO lesions intervened by a single operator with an antegrade-based technique between August 2014 and July 2020. Forty-seven patients with antegrade procedural failure (20 with pure antegrade wiring failure and 27 with back-up retrograde techniques) were compared to 278 patients with antegrade-only procedural success. With a median follow-up of 30.8 (16.1–48.6) months, 278 patients with procedural success were further assessed for target vessel failure (TVF: cardiac death, target vessel myocardial infarction [MI], and target lesion revascularization [TLR]). Patients with antegrade procedural success had a lower percentage of history with bypass graft (4 vs. 15%, p = 0.004) and lower Multicenter Chronic Total Occlusion Registry of Japan (J-CTO) score (2.1±1.3 vs. 3.4 ± 1.0, p < 0.001), when compared to those with antegrade failure. The J-CTO score was independently associated with procedural failure (odds ratio = 2.5, 95% CI = 1.8–3.4) in multivariate analysis. However, only clinical features, such as female gender (hazard ratio [HR] = 4.3, 95% CI = 1.4–13.1), estimated glomerular filtration rate

Abstract Aims Lower extremity arterial disease (LEAD) and left ventricular diastolic dysfunction (LVDD) share many risk factors, but the characteristics of LVDD and its association with prognosis in patients with LEAD have not been fully examined. Methods and results We investigated the impact of LVDD on the clinical outcomes in LEAD patients. LVDD was classified according to the newest suggested classification by the American Society of Echocardiography. Survival analysis for mortality (primary endpoint) and major adverse cardiac events (MACE; secondary endpoint) was calculated with all clinical variables and adjusted by multivariate Cox regression. We consecutively enrolled 221 controls and 464 LEAD patients from outpatient clinics and hospitals. The prevalence of LVDD was proportional to the severity of LEAD defined by the Rutherford class. The difference of LVDD severity is significant when compared with the control and LEAD patients or LEAD patients who underwent endovascular therapy (EVT), and it is also proportional to the LEAD severity. The grade of LVDD was a significant factor in predicting MACE and mortality in LEAD patients after multivariate Cox regression analysis [hazard ratio (HR) = 2.11, 95% CI = 1.47–2.83, P = 0.026; HR = 1.47, 95% CI = 1.02–2.02, P = 0.041]. This impact remained significant in LEAD patients who underwent EVT. Conclusions The degree of LVDD may predict MACE and mortality in LEAD patients. Whether early identification of LVDD in LEAD patients is helpful warrants further large‐scale prospective randomized studies.

Atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease, cerebrovascular disease, and peripheral artery disease, carries a high morbidity and mortality. Risk factor control is especially important for patients with ASCVD to reduce recurrent cardiovascular events. Clinical guidelines have been developed by the Taiwan Society of Cardiology, Taiwan Society of Lipids and Atherosclerosis, and Diabetes Association of Republic of China (Taiwan) to assist health care professionals in Taiwan about the control of hypertension, hypercholesterolemia and diabetes mellitus. This article is to highlight the recommendations about blood pressure, cholesterol, and sugar control for ASCVD. Some medications that are beneficial for ASCVD were also reviewed. We hope the clinical outcomes of ASCVD can be improved in Taiwan through the implementation of these recommendations. Keywords: Atherosclerosis, Risk factors, Performance guide

Pulmonary arterial hypertension (PAH) is characterized as a progressive and sustained increase in pulmonary vascular resistance, which may induce right ventricular failure. In 2014, the Working Group on Pulmonary Hypertension of the Taiwan Society of Cardiology (TSOC) conducted a review of data and developed a guideline for the management of PAH.4 In recent years, several advancements in diagnosis and treatment of PAH has occurred. Therefore, the Working Group on Pulmonary Hypertension of TSOC decided to come up with a focused update that addresses clinically important advances in PAH diagnosis and treatment. This 2018 focused update deals with: (1) the role of echocardiography in PAH; (2) new diagnostic algorithm for the evaluation of PAH; (3) comprehensive prognostic evaluation and risk assessment; (4) treatment goals and follow-up strategy; (5) updated PAH targeted therapy; (6) combination therapy and goal-orientated therapy; (7) updated treatment for PAH associated with congenital heart disease; (8) updated treatment for PAH associated with connective tissue disease; and (9) updated treatment for chronic thromboembolic pulmonary hypertension. Keywords: Guideline, Pulmonary arterial hypertension, Pulmonary hypertension

Background: Left atrial (LA) size represents atrial fibrillation (AF) burden and has been shown to be a predictor for AF stroke. The CHA2DS2-VASc score is also a well-established predictor of AF stroke. It is unknown to cardiologists whether these two risk scores are correlated, whether both are independent prognostic predictors and complimentary to each other, or whether one of them is a major determinant of stroke risk for AF patients.Method: A total of 708 patients from the National Taiwan University Atrial Fibrillation Registry were longitudinally followed up for more than 15 years. Left atrial size was measured by M mode of echocardiography. Adverse thromboembolic endpoints during follow-up were defined as ischemic stroke or transient ischemic attack.Results: The mean age was 72.1 ± 12.9 years, with 53% men. Both LA size and CHA2DS2-VASc score were associated with the risk of stroke in univariate analyses. There was a weak but significant positive correlation between LA size and CHA2DS2-VASc score (r = 0.17, P < 0.0001). Patients with higher CHA2DS2-VASc scores had a higher mean LA size (P < 0.01 for trend). When combining LA size and CHA2DS2-VASc score in the multivariable Cox model, only CHA2DS2-VASc score remained statistically significant [HR 1.39 (1.20–1.63); P < 0.001].Conclusion: LA size is not an independent predictor of AF stroke, and calculation of CHA2DS2-VASc score may be an alternative to measurement of echocardiographic LA size when evaluating the risk of stroke for AF patients.

ObjectiveWe used nationwide population-based data to identify optimal hospital and surgeon volume thresholds and to discover the effects of these volume thresholds on operative mortality and length of stay (LOS) for coronary artery bypass surgery (CABG).DesignRetrospective cohort study.SettingGeneral acute care hospitals throughout Taiwan.ParticipantsA total of 12,892 CABG patients admitted between 2011 and 2015 were extracted from Taiwan National Health Insurance claims data.Main outcome measuresOperative mortality and LOS. Restricted cubic splines were applied to discover the optimal hospital and surgeon volume thresholds needed to reduce operative mortality. Generalized estimating equation regression modeling, Cox proportional-hazards modeling and instrumental variables analysis were employed to examine the effects of hospital and surgeon volume thresholds on the operative mortality and LOS.ResultsThe volume thresholds for hospitals and surgeons were 55 cases and 5 cases per year, respectively. Patients who underwent CABG from hospitals that did not reach the volume threshold had higher operative mortality than those who received CABG from hospitals that did reach the volume threshold. Patients who underwent CABG with surgeons who did not reach the volume threshold had higher operative mortality and LOS than those who underwent CABG with surgeons who did reach the volume threshold.ConclusionsThis is the first study to identify the optimal hospital and surgeon volume thresholds for reducing operative mortality and LOS. This supports policies regionalizing CABG at high-volume hospitals. Identifying volume thresholds could help patients, providers, and policymakers provide optimal care.

(1) Background: The role of using artificial intelligence (AI) with electrocardiograms (ECGs) for the diagnosis of significant coronary artery disease (CAD) is unknown. We first tested the hypothesis that using AI to read ECG could identify significant CAD and determine which vessel was obstructed. (2) Methods: We collected ECG data from a multi-center retrospective cohort with patients of significant CAD documented by invasive coronary angiography and control patients in Taiwan from 1 January 2018 to 31 December 2020. (3) Results: We trained convolutional neural networks (CNN) models to identify patients with significant CAD (>70% stenosis), using the 12,954 ECG from 2303 patients with CAD and 2090 ECG from 1053 patients without CAD. The Marco-average area under the ROC curve (AUC) for detecting CAD was 0.869 for image input CNN model. For detecting individual coronary artery obstruction, the AUC was 0.885 for left anterior descending artery, 0.776 for right coronary artery, and 0.816 for left circumflex artery obstruction, and 1.0 for no coronary artery obstruction. Marco-average AUC increased up to 0.973 if ECG had features of myocardial ischemia. (4) Conclusions: We for the first time show that using the AI-enhanced CNN model to read standard 12-lead ECG permits ECG to serve as a powerful screening tool to identify significant CAD and localize the coronary obstruction. It could be easily implemented in health check-ups with asymptomatic patients and identifying high-risk patients for future coronary events.

Background: Brugada syndrome (BrS) is a rare inherited disease causing sudden cardiac death (SCD). Copy number variants (CNVs) can contribute to disease susceptibility, but their role in Brugada syndrome (BrS) is unknown. We aimed to identify a CNV associated with BrS and elucidated its clinical implications. Methods: We enrolled 335 unrelated BrS patients from 2000 to 2018 in the Taiwanese population. Microarray and exome sequencing were used for discovery phase whereas Sanger sequencing was used for the validation phase. HEK cells and zebrafish were used to characterize the function of the CNV variant. Findings: A copy number deletion of GSTM3 (chr1:109737011-109737301, hg38) containing the eighth exon and the transcription stop codon was observed in 23.9% of BrS patients versus 0.8% of 15,829 controls in Taiwan Biobank (P < 0.001), and 0% in gnomAD. Co-segregation analysis showed that the co-segregation rate was 20%. Patch clamp experiments showed that in an oxidative stress environment, GSTM3 down-regulation leads to a significant decrease of cardiac sodium channel current amplitude. Ventricular arrhythmia incidence was significantly greater in gstm3 knockout zebrafish at baseline and after flecainide, but was reduced after quinidine, consistent with clinical observations. BrS patients carrying the GSTM3 deletion had higher rates of sudden cardiac arrest and syncope compared to those without (OR: 3.18 (1.77–5.74), P

In Taiwan, the incidence of non-ST segment elevation acute coronary syndrome (NSTE-ACS) continues to increase in recent years. The purpose of this guideline is to help health care professionals in Taiwan to use adequate tests and treatments for management of NSTE-ACS. For rapid diagnosis, in addition to history and physical examination, 0/3 h rapid diagnosis protocol with high sensitivity cardiac troponin assay is recommended in this guideline. Dual antiplatelet and anticoagulation therapies are important parts in the initial treatment. Risk stratification should be performed to identify high risk patients for early coronary angiography. Through evaluation of the coronary anatomy and other clinical factors, the decision for coronary revascularization, either by percutaneous coronary intervention or coronary artery bypass grafting, should be decided by the heart team. The duration of dual antiplatelet therapy should be given for at least 12 months after discharge. Other secondary preventive medications are also recommended for long term use. Keywords: Acute coronary syndrome, Guideline, Taiwan

Background: Among various bio-informative molecules transferred by exosomes between cells, micro RNAs (miRNAs), which remain remarkably stable even after freeze-and-thaw cycles, are excellent candidates for potential biomarkers for coronary artery disease (CAD). Methods: Blood samples were collected from the coronary arteries of 214 patients diagnosed with three-vessel CAD and 140 without CAD. After precipitation extraction, the amounts of exosomes were found to decrease with increased age and three-vessel CAD. Next-generation sequencing was performed to further explore the possible relationship between exosomal miRNAs and CAD. Results: Eight exosomal miRNAs showed altered expression associated with CAD. The up-regulated miRNAs in CAD were miRNA-382-3p, miRNA-432-5p, miRNA-200a-3p, and miRNA-3613-3p. The down-regulated miRNAs were miRNA-125a-5p, miRNA-185-5p, miRNA-151a-3p, and miRNA-328-3p. Conclusion: We successfully demonstrated particular exosomal miRNAs that may serve as future biomarkers for CAD.

Summary: Several studies have shown the beneficial effect of renal denervation (RDN) in the treatment of ventricular arrhythmia, especially in the setting of heart failure (HF). However, the underlying mechanism of antiarrhythmic effect of RDN is unknown. Arrhythmogenic cardiac alternans, particularly spatially discordant repolarization alternans, characterized by simultaneous prolongation and shortening of action potential duration (APD) in different myocardial regions, is central to the genesis of ventricular fibrillation in HF. Whether RDN decreases the susceptibility to arrhythmogenic cardiac alternans in HF has never been addressed before. The authors used a rat model of post-myocardial infarction HF and dual voltage-calcium optical mapping to investigate whether RDN could attenuate arrhythmogenic cardiac alternans that predisposes to ventricular arrhythmias, as well as the hemodynamic effect of RDN in HF. The HF rats had increased body weights, dilated hearts, and lower blood pressure. The HF rats also had longer ventricular APDs and a delay in the decay of the calcium transient, typical electrophysiological features of human HF. Susceptibility to calcium transient alternans, APD alternans, and spatially discordant APD alternans was increased in the HF hearts. RDN significantly attenuated a delay in the decay of the calcium transient, calcium transient and APD alternans, and importantly, the discordant APD alternans, and thereby decreased the incidence of induced ventricular arrhythmia in HF. RDN did not further decrease blood pressure in HF rats. In conclusion, RDN improves calcium cycling and prevents spatially discordant APD alternans and ventricular arrhythmia in HF. RDN does not aggravate hemodynamics in HF. Key Words: alternans, arrhythmia mechanism, heart failure, renal denervation

Background The aim of this study was to determine the influence of various antidiabetic therapies on the relationship between body mass index and all‐cause mortality in patients with diabetes mellitus and acute coronary syndrome. Methods and Results This was a prospective, observational study comprising 1193 patients diagnosed with type 2 diabetes mellitus and acute coronary syndrome. The patients were stratified into 4 body mass index categories, and their mortality rates were compared using time‐dependent Cox regression analysis using normal weight (body mass index, 18.5–23.9) as the reference. Subsequently, the influence of antidiabetic therapies on the association between BMI and mortality were analyzed. Seventy‐four patients (6.2%) died over 2 years of follow‐up. The mortality rate was lowest in the class I obese group (3.35%) and highest in the normal‐weight group (9.67%). After adjusting for covariates, class I obesity paradoxically remained significantly protective against mortality compared with normal weight (hazard ratio, 0.141; P=0.049); interaction term analysis showed that insulin therapy influenced this “obesity paradox” (P=0.045). When the patients were stratified by insulin use, the protective effect of obesity disappeared in the insulin‐treated patients but persisted in the non–insulin‐treated patients. Conclusions In patients with type 2 diabetes mellitus and acute coronary syndrome, the relationship between body mass index and mortality rate is U‐shaped, with class I obesity representing the nadir and normal weight the peak. The protective effect of obesity disappeared in patients treated with insulin.

Ischemic neuron loss contributes to brain dysfunction in patients with cardiac arrest (CA). Histidine-tryptophan-ketoglutarate (HTK) solution is a preservative used during organ transplantation. We tested the potential of HTK to protect neurons from severe hypoxia (SH) following CA. We isolated rat primary cortical neurons and induced SH with or without HTK. Changes in caspase-3, hypoxia-inducible factor 1-alpha (HIF-1α), and nicotinamide adenine dinucleotide phosphate oxidase-4 (NOX4) expression were evaluated at different time points up to 72 h. Using a rat asphyxia model, we induced CA-mediated brain damage and then completed resuscitation. HTK or sterile saline was administered into the left carotid artery. Neurological deficit scoring and mortality were evaluated for 3 days. Then the rats were sacrificed for evaluation of NOX4 and H2O2 levels in blood and brain. In the in vitro study, HTK attenuated SH- and H2O2-mediated cytotoxicity in a volume- and time-dependent manner, associated with persistent HIF-1α expression and reductions in procaspase-3 activation and NOX4 expression. The inhibition of HIF-1α abrogated HTK's effect on NOX4. In the in vivo study, neurological scores were significantly improved by HTK. H2O2 level, NOX4 activity, and NOX4 gene expression were all decreased in the brain specimens of HTK-treated rats. Our results suggest that HTK acts as an effective neuroprotective solution by maintaining elevated HIF-1α level, which was associated with inhibited procaspase-3 activation and decreased NOX4 expression.

Brugada syndrome (BrS) is a heritable disease that results in sudden cardiac death. In the exome/genomic era, certain reported pathogenic variants in some genetic diseases have been reclassified as benign owing to their high frequency in some ancestries. In the present study, we comprehensively reassessed all previously reported pathogenic variants of BrS. We collected all pathogenic variants of BrS reported in the Human Gene Mutation Database and ClinVar throughout April 2017. We compared the minor allele frequency (MAF) of each variant among different ancestries by searching public whole-genome and exome databases. After considering the maximum credible allele frequency, variants with a MAF ≥ 0.001 were considered to be of questionable pathogenicity. We also investigated the percentage of SCN5A variants with a MAF ≥ 0.001 in 124 BrS patients from the Han Chinese population. We collected a total of 440 BrS variants, of which 18 had a MAF ≥ 0.001. There was a greater percentage of non-SCN5A variants with a MAF ≥ 0.001 than of SCN5A variants (21.8 versus 1.6%, p < 0.0001). There were fewer frameshift and nonsense mutations than missense mutations (0.9 versus 5.6%, p = 0.032). Of the 18 variants, 14 (77.8%) were present only in the reference Asian population. In our cohort, we identified two SCN5A variants (p.A226V and p.V1340I) with MAFs ≥ 0.001 (0.45%). In conclusion, ancestral differences are important when considering the pathogenicity of BrS variants, especially in the case of missense variants and non-SCN5A variants, which may be pathogenic in some ancestries but only disease-predisposing in others.

Diabetes mellitus has reached epidemic proportion worldwide. One of the diabetic complications is cardiomyopathy, characterized by early left ventricular (LV) diastolic dysfunction, followed by development of systolic dysfunction and ventricular dilation at a late stage. The pathogenesis is multifactorial, and there is no effective treatment yet. In recent years, 4-hydroxy-2-nonenal (4-HNE), a toxic aldehyde generated from lipid peroxidation, is implicated in the pathogenesis of cardiovascular diseases. Its high bioreactivity toward proteins results in cellular damage. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is the major enzyme that detoxifies 4-HNE. The development of small-molecule ALDH2 activator provides an opportunity for treating diabetic cardiomyopathy. This study found that AD-9308, a water-soluble andhighly selective ALDH2 activator, can improve LV diastolic and systolic functions, and wall remodeling in streptozotocin-induced diabetic mice. AD-9308 treatment dose-dependently lowered serum 4-HNE levels and 4-HNE protein adducts in cardiac tissue from diabetic mice, accompanied with ameliorated myocardial fibrosis, inflammation, and apoptosis. Improvements of mitochondrial functions, sarco/endoplasmic reticulumcalcium handling and autophagy regulation were also observed in diabetic mice with AD-9308 treatment. In conclusion, ADLH2 activation effectively ameliorated diabetic cardiomyopathy, which may be mediated through detoxification of 4-HNE. Our findings highlighted the therapeutic potential of ALDH2 activation for treating diabetic cardiomyopathy.

Renal supportive care (RSC) denotes a care program dedicated for patients with acute, chronic renal failure, and end-stage renal disease (ESRD), aiming to offer maximal symptom relief and optimize patients' quality of life. The uncertainty of prognosis for patients with chronic kidney disease and ESRD, the sociocultural issues inherent to the Taiwanese society, and the void of structured and practical RSC pathway, contributes to the underrecognition and poor utilization of RSC. Taiwanese patients rarely receive information regarding RSC as part of a standardized care and are not commonly offered this option. In National Taiwan University Hospital Jinshan branch, we started a RSC subprogram, supported by the community-based palliative/hospice care main program. We focused on understanding the need and providing the choice of RSC to suitable candidates. A three-step and four-phase protocol was designed and implemented to identify appropriate patients and to enhance the applicability of the RSC. We harnessed family visit and home-based family meeting as a vehicle to understand the patients' preferences, to discover what ESRD patients and their family value most, and to introduce the option of RSC. In the current review, we described our pilot experience of establishing a RSC program in Taiwan, and discuss its potential advantage.

Tsai et al. here utilize a multi-stage genome-wide association study in Taiwanese population to show a copy number variation in the intron of potassium interacting channel 1 gene (KCNIP1) to be strongly associated with atrial fibrillation. The study also examines the functionality of KCNIP1 in heart electrophysiological function using cultured myocytes and zebrafish.