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Abstract Although several studies have demonstrated the cardiovascular (CV) implication of hypoalbuminemia and arterial calcification among hemodialysis patients, little is known regarding their cardiac correlates and relevant CV outcomes in asymptomatic individuals. We assessed the potential CV interrelation between serum albumin (SA) and aortic calcification. Among 2,723 asymptomatic individuals underwent cardiovascular health check-up, we assessed serum albumin (SA) level, thoracic aortic calcification (TAC) and coronary artery calcification (CAC) by multi-detector computed tomography, and ultrasound-determined carotid plaque burden. We related these measures to cardiac structure/function and CV outcomes. Lower SA level was associated with higher TAC score and volume rather than carotid plaque or coronary calcification burden in fully adjusted models. By categorizing the study population into 4 groups by SA (>, ≤ 4.6 mg/dL) and presence of TAC, subjects classified into low SA/TAC(+) category were oldest with highest prevalent CV disease. Both lower SA and TAC(+) were independently associated with impaired myocardial systolic/diastolic mechanics and higher CV events during a median of 6.6 years (IQR: 5.1, 6.8 years) follow-up. Participants classified into low SA/TAC(+) category showed highest risk for CV events (adjusted HR: 3.78 [95% CI: 2.11, 6.77], high SA/TAC[-] as reference) in fully adjusted Cox model. Among symptom-free individuals, TAC was closely associated with low SA concentration in relation to unfavorable cardiac mechanics and may serve as a useful prognosticator for adverse CV events.

Background: Chronic fatigue syndrome (CFS) has been linked to several conditions, including infections, immune system changes, or emotional stress. Our study aimed to assess the risk of CFS after a pneumonia diagnosis using data from National Health Insurance Research Database of Taiwan. Methods: In this nested case-control study, we identified 2,000,000 adult patients from a nationwide population-based health insurance claims database spanning from January 1, 2000, to December 31, 2017. Each case diagnosed with a pathogenic infection was matched with a corresponding control using propensity scores. We excluded individuals under 20 years of age, those with a history of pathogenic infections before the index date, or those with more than one potential pathogen. To estimate hazard ratios (HR) and the adjusted hazard ratio (aHR) with their respective 95 % confidence intervals (CI), we applied univariable and multivariable Cox proportional hazard models. The multivariable analysis incorporated adjustments for age, sex, and comorbidity-related confounders. Results: The relationship between infection and the subsequent risk of CFS was assessed using Cox proportional hazards regression analysis. The incidence density rates were 6.13 and 8.70 per 1000 person‐years among the non‐pulmonary infection and pulmonary infection populations, respectively (adjusted hazard ratio [HR] = 1.4, 95 % confidence interval [CI] 1.32–1.5). Patients infected with Pseudomonas, Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, and influenza virus exhibited a significantly higher risk of CFS than those without these pathogens (p

Abstract Peripheral artery disease (PAD) shares common clinical risk factors, for example, endothelial dysfunction, with preserved ejection fraction (LVEF) heart failure (HFpEF). Whether PAD is associated with preclinical systolic dysfunction and higher HF risk among individuals presenting preserved LVEF remains uncertain. We retrospectively included outpatients with at least one known or established cardiovascular (CV) risk factor with LVEF ≥ 50%. Patients were categorized into high risk and low risk of developing PAD (PAD vs Non-PAD) by ankle-brachial index (ABI) (≤ 0.90 or > 1.4) and further stratified based on their history of HFpEF (HFpEF vs. Non-HFpEF), resulting in the formation of four distinct strata. Preclinical systolic dysfunction was defined using dedicated speckle-tracking algorithm. A total of 2130 consecutive patients were enrolled in the study, with a median follow-up of 4.4 years. The analysis revealed a higher prevalence of high risk of developing PAD in patients with HFpEF compared to those without HFpEF (25.1% vs. 9.4%). Both high risk of developing PAD and HFpEF were independently associated with preclinical systolic dysfunction (global longitudinal strain, GLS ≥ − 18%) (odds ratio, OR: 1.38; 95% confidence interval, CI: 1.03–1.86). In comparison to patients at low risk of developing PAD without HFpEF (Non-PAD/Non-HFpEF group), those categorized as having a high risk of developing PAD with HFpEF (PAD/HFpEF group) exhibited the most impaired GLS and a heightened susceptibility to heart failure hospitalization (hazard ratio, HR: 6.51; 95% CI: 4.43–9.55), a twofold increased risk of all-cause mortality (HR: 2.01; 95% CI: 1.17–3.38), cardiovascular mortality (HR: 2.44; 95% CI: 1.08–5.51), and non-cardiovascular mortality (HR: 1.78; 95% CI: 0.82–3.84). A high risk of developing PAD was strongly linked to impaired preclinical systolic function and an increased likelihood for subsequent hospitalization for HF, all-cause mortality, CV mortality and non-CV mortality. There is a clear need for preventive strategies aimed at reducing hospitalizations for HF and mortality in this high-risk population.

Sleep disordered breathing (SDB) is highly prevalent and may be linked to cardiovascular disease in a bidirectional manner. The Taiwan Society of Cardiology, Taiwan Society of Sleep Medicine and Taiwan Society of Pulmonary and Critical Care Medicine established a task force of experts to evaluate the evidence regarding the assessment and management of SDB in patients with atrial fibrillation (AF), hypertension and heart failure with reduced ejection fraction (HFrEF). The GRADE process was used to assess the evidence associated with 15 formulated questions. The task force developed recommendations and determined strength (Strong, Weak) and direction (For, Against) based on the quality of evidence, balance of benefits and harms, patient values and preferences, and resource use. The resulting 11 recommendations are intended to guide clinicians in determining which the specific patient-care strategy should be utilized by clinicians based on the needs of individual patients.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

Background Dapagliflozin, a sodium–glucose cotransporter 2 inhibitor, is an epochal oral antidiabetic drug that improves cardiorenal outcomes. However, the effect of early dapagliflozin intervention on left ventricular (LV) remodeling in patients with type 2 diabetes free from cardiovascular disease remains unclear. Methods and Results The ELUCIDATE trial was a prospective, open‐label, randomized, active‐controlled study that enrolled 76 patients with asymptomatic type 2 diabetes with LV ejection fraction ≥50%, randomized to the dapagliflozin 10 mg/day add‐on or standard‐of‐care group. Speckle‐tracking echocardiography–based measurements of the cardiac global longitudinal strain were performed at baseline and 24 weeks after treatment initiation. Patients who received dapagliflozin had a greater reduction in LV dimension (1.68 mm [95% CI, 0.53–2.84]; P=0.005), LV end‐systolic volume (5.51 mL [95% CI, 0.86–10.17]; P=0.021), and LV mass index (4.25 g/m2.7 [95% CI, 2.42–6.09]; P

Background This study investigated whether initial SGLT2 (sodium‐glucose cotransporter 2) inhibitor‐based treatment is superior to metformin‐based regimens as a primary prevention strategy among low‐risk patients with diabetes. Methods and Results In this nationwide cohort study, a total of 38 496 patients with diabetes with low cardiovascular risk were identified (age 62.0±11.6 years, men 50%) from January 1 to December 31, 2016. Patients receiving SGLT2 inhibitors‐based and metformin‐based regimens were 1:2 matched by propensity score. Study outcomes included all‐cause mortality, cardiovascular death, hospitalization for heart failure, stroke, and progression to end‐stage renal disease. Compared with 1928 patients receiving metformin‐based regimens, 964 patients receiving SGLT2 inhibitor‐based regimens had similar all‐cause mortality (hazard ratio [HR], 0.75 [95% CI, 0.51–1.12]), cardiovascular death (HR, 0.69 [95% CI, 0.25–1.89]), hospitalization for heart failure (HR, 1.06 [95% CI, 0.59–1.92]), stroke (HR, 0.78 [95% CI, 0.48–1.27]), and progression to end‐stage renal disease (HR, 0.88 [95% CI, 0.32–2.39]). However, SGLT2 inhibitors were associated with a lower risk of all‐cause mortality (HR, 0.47 [95% CI, 0.23–0.99]; P for interaction=0.008) and progression to end‐stage renal disease (HR, 0.22 [95% CI, 0.06–0.82]; P for interaction=0.04) in patients under the age of 65. Conclusions In comparison to metformin‐based regimens, SGLT2 inhibitor‐based regimens showed a similar risk of all‐cause mortality and adverse cardiorenal events. SGLT2 inhibitors might be considered as first‐line therapy in select low‐risk patients, for example, younger patients with diabetes.

Abstract Sodium-glucose cotransporter type 2 (SGLT2) inhibitors have demonstrated to reduce cardiovascular risk in patients with type 2 diabetes mellitus (T2DM) in large trials independent of glycemic control. The mechanisms of this cardioprotective property remain uncertain. Evidence suggests positive hemodynamic changes and favorable cardiac remodeling contributing to the clinical outcomes but results were conflicting. We aim to investigate the potential impact on hemodynamic parameters, cardiac structure and functions. This prospective observational study included T2DM patients receiving canagliflozin 100 mg per day in addition to their antidiabetic treatment. We analyzed hemodynamic parameters assessed by echocardiographic measurements and impedance cardiography (ICG) to evaluate systolic and diastolic functions from baseline to 24 weeks after treatment. A total of 47 patients (25 males and 22 females) averaging 64.6 ± 10.9 years had a significant reduction in HbA1c, body weight, and systolic blood pressure. Hematocrit increased significantly, while NT-proBNP remained unchanged. E/e′, left atrium (LA) volume, and LA stiffness were reduced, while left ventricle (LV) global longitudinal strain (GLS) and LA strain rates increased at 24 weeks by conventional and speckle tracking echocardiography. LV mass and ejection fraction showed no differences. ICG suggested significant improvement in hemodynamic parameters with increased stroke volume index and cardiac output index and decreased systemic vascular resistance index at 12 and 24 weeks. Canagliflozin improved hemodynamic parameters and had a favorable impact on LA and LV reverse remodeling. These changes may explain the beneficial effect on cardiovascular outcomes in large clinical trials.

Abstract Background Previous serological studies have indicated an association between viruses and atypical pathogens and Chronic Fatigue Syndrome (CFS). This study aims to investigate the correlation between infections from common pathogens, including typical bacteria, and the subsequent risk of developing CFS. The analysis is based on data from Taiwan’s National Health Insurance Research Database. Methods From 2000 to 2017, we included a total of 395,811 cases aged 20 years or older newly diagnosed with infection. The cases were matched 1:1 with controls using a propensity score and were followed up until diagnoses of CFS were made. Results The Cox proportional hazards regression analysis was used to estimate the relationship between infection and the subsequent risk of CFS. The incidence density rates among non-infection and infection population were 3.67 and 5.40 per 1000 person‐years, respectively (adjusted hazard ratio [HR] = 1.5, with a 95% confidence interval [CI] 1.47–1.54). Patients infected with Varicella-zoster virus, Mycobacterium tuberculosis, Escherichia coli, Candida, Salmonella, Staphylococcus aureus and influenza virus had a significantly higher risk of CFS than those without these pathogens (p

Abstract Chronic heavy alcohol use is associated with lethal arrhythmias. Whether common East Asian-specific aldehyde dehydrogenase deficiency (ALDH2*2) contributes to arrhythmogenesis caused by low level alcohol use remains unclear. Here we show 59 habitual alcohol users carrying ALDH2 rs671 have longer QT interval (corrected) and higher ventricular tachyarrhythmia events compared with 137 ALDH2 wild-type (Wt) habitual alcohol users and 57 alcohol non-users. Notably, we observe QT prolongation and a higher risk of premature ventricular contractions among human ALDH2 variants showing habitual light-to-moderate alcohol consumption. We recapitulate a human electrophysiological QT prolongation phenotype using a mouse ALDH2*2 knock-in (KI) model treated with 4% ethanol, which shows markedly reduced total amount of connexin43 albeit increased lateralization accompanied by markedly downregulated sarcolemmal Nav1.5, Kv1.4 and Kv4.2 expressions compared to EtOH-treated Wt mice. Whole-cell patch-clamps reveal a more pronounced action potential prolongation in EtOH-treated ALDH2*2 KI mice. By programmed electrical stimulation, rotors are only provokable in EtOH-treated ALDH2*2 KI mice along with higher number and duration of ventricular arrhythmia episodes. The present research helps formulate safe alcohol drinking guideline for ALDH2 deficient population and develop novel protective agents for these subjects.

Abstract Objective An increased prevalence of psychiatric comorbidities (including depression and anxiety disorder) has been observed among patients with chronic fatigue syndrome (CFS). However, few studies have examined the presence of depression and anxiety disorder before the diagnosis of CFS. This study aimed to clarify the preexisting comorbidities and treatments associated with patients with subsequent CFS diagnosis in a population-based cohort in Taiwan. Methods An analysis utilizing the National Health Insurance Research Database of Taiwan was conducted. Participants included were 6303 patients with CFS newly diagnosed between 2000 and 2010 and 6303 age-/sex-matched controls. Results Compared with the control group, the CFS group had a higher prevalence of depression and anxiety disorder before the diagnosis of CFS. Sampled patients who took specific types of antidepressants, namely, selective serotonin reuptake inhibitors (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] 1.04–1.39), serotonin antagonists and reuptake inhibitors (SARI; aOR = 1.87, 95% CI 1.59–2.19), and tricyclic antidepressants (aOR = 1.46, 95% CI 1.09–1.95), had an increased risk of CFS. CFS risk was also higher among participants taking benzodiazepine, muscle relaxants, and analgesic drugs. A sub-group analysis revealed that SARI use was related to an increased risk of CFS in the depression, anxiety disorder, male, and female groups. In the depression and anxiety disorder groups, analgesic drug use was associated with an increased CFS risk. Nonpharmacological treatment administration differed between men and women. Conclusion This population-based retrospective cohort study revealed an increased risk of CFS among populations with preexisting depression and anxiety disorder, especially those taking SARI and analgesic drugs.

Background The angiotensin receptor–neprilysin inhibitor (LCZ696) has emerged as a promising pharmacological intervention against renin–angiotensin system inhibitor in reduced ejection fraction heart failure (HFrEF). Whether the therapeutic benefits may vary among heterogeneous HFrEF subgroups remains unknown. Methods and Results This study comprised a pooled 2‐center analysis including 1103 patients with symptomatic HFrEF with LCZ696 use and another 1103 independent HFrEF control cohort (with renin–angiotensin system inhibitor use) matched for age, sex, left ventricular ejection fraction, and comorbidity conditions. Three main distinct phenogroup clusterings were identified from unsupervised machine learning using 29 clinical variables: phenogroup 1 (youngest, relatively lower diabetes prevalence, highest glomerular filtration rate with largest left ventricular size and left ventricular wall stress); phenogroup 2 (oldest, lean, highest diabetes and vascular diseases prevalence, lowest highest glomerular filtration rate with smallest left ventricular size and mass), and phenogroup 3 (lowest clinical comorbidity with largest left ventricular mass and highest hypertrophy prevalence). During the median 1.74‐year follow‐up, phenogroup assignment provided improved prognostic discrimination beyond Meta‐Analysis Global Group in Chronic Heart Failure risk score risk score (all net reclassification index P

Background: This study aims to explore the clinical correlates of myocardial deformations using speckle-tracking algorithm and to determine the prognostic utility of such measures in asymptomatic ethnic Chinese population. Methods: Global longitudinal (GLS), circumferential strain (GCS), and torsion were analyzed using featured tissue-tracking algorithm among 4049 symptom-free ethnic Chinese population. Hypertrophy (LVH) was classified into 4 tiers: indeterminate, dilated, thick and thick/dilated, by gender-stratified partition of end-diastolic volume index (EDVi) and LV mass/EDV0.67. Results: LVH (7.3%) showed substantially lower GLS (−20.3 ± 1.82% vs. −18.9 ± 2.08%) yet higher torsion (2.20 ± 0.90 vs. 2.39 ± 1.01, p

Abstract Visceral adipose tissue (VAT) is associated with central obesity, insulin resistance and metabolic syndrome. However, the association of body-site specific adiposity and non-alcoholic fatty liver disease (NAFLD) has not been well characterized. We studies 704 consecutive subjects who underwent annual health survey in Taiwan. All subjects have been divided into three groups including normal (341), mild (227) and moderate and severe (136) NAFLD according to ultrasound finding. Pericardial (PCF) and thoracic peri-aortic adipose tissue (TAT) burden was assessed using a non-contrast 16-slice multi-detector computed tomography (MDCT) dataset with off-line measurement (Aquarius 3DWorkstation, TeraRecon, SanMateo, CA, USA). We explored the relationship between PCF/TAT, NAFLD and cardiometabolic risk profiles. Patients with moderate and mild NAFLD have greater volume of PCF (100.7 ± 26.3vs. 77.1 ± 21.3 vs. 61.7 ± 21.6 ml, P

BackgroundFew studies have addressed early-stage kidney disease and preclinical cardiac structural and functional abnormalities from a large-scale Asian population. Further, the extent to which measures of myocardial function and whether these associations may vary by testing various formulas of renal insufficiency remains largely unexplored.ObjectiveTo explore the associations among renal function, proteinuria, and left ventricular (LV) structural and diastolic functional alterations.DesignA cross-sectional, retrospective cohort study.SettingRegistered data from a cardiovascular health screening program at MacKay Memorial Hospital from June 2009 to December 2012.ParticipantsAsymptomatic individuals.MeasurementsRenal function was evaluated in terms of estimated glomerular filtration rate (eGFR) by both MDRD and CKD-EPI formulas and severity of proteinuria, which were further related to cardiac structure, diastolic function (including LV e’ by tissue Doppler), and circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) level.ResultsAmong 4942 participants (65.8% men, mean age 49.4 ± 11.2 years), the mean CKD-EPI/MDRD eGFR was 90.6 ± 15.7 and 88.5 ± 16.9 ml/min/1.73m2, respectively. Lower eGFR, estimated either by the MDRD or CKD-EPI method, and higher proteinuria were significantly associated with lower LV e’ and higher NT-proBNP (all p

Summary: Background: Echocardiography (echo) based machine learning (ML) models may be useful in identifying patients at high-risk of all-cause mortality. Methods: We developed ML models (ResNet deep learning using echo videos and CatBoost gradient boosting using echo measurements) to predict 1-year, 3-year, and 5-year mortality. Models were trained on the Mackay dataset, Taiwan (6083 echos, 3626 patients) and validated in the Alberta HEART dataset, Canada (997 echos, 595 patients). We examined the performance of the models overall, and in subgroups (healthy controls, at risk of heart failure (HF), HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF)). We compared the models' performance to the MAGGIC risk score, and examined the correlation between the models’ predicted probability of death and baseline quality of life as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). Findings: Mortality rates at 1-, 3- and 5-years were 14.9%, 28.6%, and 42.5% in the Mackay cohort, and 3.0%, 10.3%, and 18.7%, in the Alberta HEART cohort. The ResNet and CatBoost models achieved area under the receiver-operating curve (AUROC) between 85% and 92% in internal validation. In external validation, the AUROCs for the ResNet (82%, 82%, and 78%) were significantly better than CatBoost (78%, 73%, and 75%), for 1-, 3- and 5-year mortality prediction respectively, with better or comparable performance to the MAGGIC score. ResNet models predicted higher probability of death in the HFpEF and HFrEF (30%–50%) subgroups than in controls and at risk patients (5%–20%). The predicted probabilities of death correlated with KCCQ scores (all p

Abstract Detailed descriptions of acute pulmonary emboli (PE) morphology, total embolic volume (TEV), and their effects upon patients’ clinical presentation and prognosis remain largely unexplored. We studied 201 subjects with acute PE to the emergency department of a single medical center from April 2009 to December 2014. Patient hemodynamics, Troponin I and D-dimer levels, echocardiography, and the 30-day, 90-day and long-term mortality were obtained. Contrast-enhanced computed tomography (CT) of pulmonary structures and 3-dimensional measures of embolic burden were performed. The results showed a linear association between the greater TEV and each of the following 4 variables (increasing incidence of right ventricular (RV) dysfunction, higher systolic pulmonary artery pressure (sPAP), greater RV diameter, and RV/left ventricular (LV) ratio (all p

Abstract Background The circadian system is responsible for regulating various physiological activities and behaviors and has been gaining recognition. The circadian rhythm is adjusted in a 24-h cycle and has transcriptional–translational feedback loops. When the circadian rhythm is interrupted, affecting the expression of circadian genes, the phenotypes of diseases could amplify. For example, the importance of maintaining the internal temporal homeostasis conferred by the circadian system is revealed as mutations in genes coding for core components of the clock result in diseases. This study will investigate the association between circadian genes and metabolic syndromes in a Taiwanese population. Methods We performed analysis using whole-genome sequencing, read vcf files and set target circadian genes to determine if there were variants on target genes. In this study, we have investigated genetic contribution of circadian-related diseases using population-based next generation whole genome sequencing. We also used significant SNPs to create a metabolic syndrome prediction model. Logistic regression, random forest, adaboost, and neural network were used to predict metabolic syndrome. In addition, we used random forest model variables importance matrix to select 40 more significant SNPs, which were subsequently incorporated to create new prediction models and to compare with previous models. The data was then utilized for training set and testing set using five-fold cross validation. Each model was evaluated with the following criteria: area under the receiver operating characteristics curve (AUC), precision, F1 score, and average precision (the area under the precision recall curve). Results After searching significant variants, we used Chi-Square tests to find some variants. We found 186 significant SNPs, and four predicting models which used 186 SNPs (logistic regression, random forest, adaboost and neural network), AUC were 0.68, 0.8, 0.82, 0.81 respectively. The F1 scores were 0.412, 0.078, 0.295, 0.552, respectively. The other three models which used the 40 SNPs (logistic regression, adaboost and neural network), AUC were 0.82, 0.81, 0.81 respectively. The F1 scores were 0.584, 0.395, 0.574, respectively. Conclusions Circadian gene defect may also contribute to metabolic syndrome. Our study found several related genes and building a simple model to predict metabolic syndrome.

Background Fragmented QRS (fQRS) morphology as a surrogate marker of the possible presence of myocardial scarring has been shown to confer a higher risk in patients with reduced ejection fraction heart failure. We aimed to investigate the pathophysiological correlates and prognostic implications of fQRS in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results We consecutively studied 960 patients with HFpEF (76.4±12.7 years, men: 37.2%). fQRS was assessed using a body surface ECG during hospitalization. QRS morphology was available and classified into 3 categories among 960 subjects with HFpEF as non‐fQRS, inferior fQRS, and anterior/lateral fQRS groups. Despite comparable clinical features in most baseline demographics among the 3 fQRS categories, anterior/lateral fQRS showed significantly higher B‐type natriuretic peptide/troponin levels (both 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

Abstract Background This study investigated temporal trends in the treatment and mortality of patients with cardiogenic shock (CS) in Taiwan in relation to acute myocardial infarction (AMI) accreditation implemented in 2009 and the unavailability of percutaneous ventricular assist devices. Methods Data of patients diagnosed as having CS between January 2003 and December 2017 were collected from Taiwan’s National Health Insurance Research Database. Each case was followed from the date of emergency department arrival or hospital admission for the first incident associated with a CS diagnosis up to a 1-year interval. Measurements included demographics, comorbidities, treatment, mortality, and medical costs. Using an interrupted time-series (ITS) design with multi-level mixed-effects logistic regression model, we assessed the impact of AMI accreditation implementation on the mortality of patients with AMI and CS overall and stratified by the hospital levels. Results In total, 64 049 patients with CS (mean age:70 years; 62% men) were identified. The incidence rate per 105 person-years increased from 17 in 2003 to 25 in 2010 and plateaued thereafter. Average inpatient costs increased from 159 125 points in 2003 to 240 993 points in 2017, indicating a 1.5-fold increase. The intra-aortic balloon pump application rate was approximately 22–25% after 2010 (p = 0.093). Overall, in-hospital, 30-day, and 1-year mortality declined from 60.3%, 63.0%, and 69.3% in 2003 to 47.9%, 50.8% and 59.8% in 2017, respectively. The decline in mortality was more apparent in patients with AMI-CS than in patients with non-AMI-CS. The ITS estimation revealed a 2% lower in-hospital mortality in patients with AMI-CS treated in district hospitals after the AMI accreditation had been implemented for 2 years. Conclusions In Taiwan, the burden of CS has consistently increased due to high patient complexity, advanced therapies, and stable incidence. Mortality declined over time, particularly in patients with AMI-CS, which may be attributable to advancements in AMI therapies and this quality-improving policy.

Abstract Background This study assessed the performance of visceral adiposity index and body shape index in predicting diabetes mellitus (DM) risk and compared their predictive ability to that of body mass index and waist circumference. Methods Among 8249 consecutive subjects who attended the Nationwide Health Check Up System for Senior Citizens (≥ 65 years) between 2008 and 2018, we examined the associations of several adiposity indices with DM risk and explored gender differences. Results Among all adiposity indicators, Chinese visceral adiposity index (CVAI) demonstrated the highest discriminatory ability for diabetes mellitus with area under receiver operating characteristic curves (AUC) of 0.65, 0.68, and 0.66 for men, women, and all participants, respectively, and optimal cut-offs set as 126.09 in men and 117.77 in women. Compared with body shape index (ABSI), both CVAI and VAI were strongly associated with baseline DM (adjusted OR: 4.85, 95% CI: 4.05–5.82 and 4.22, 95% CI: 3.53–5.05 for 4th vs 1st quartile groups by CVAI and VAI, P

Abstract There is an established link between cardiometabolic abnormality, central arterial stiffness, and preserved ejection fraction heart failure (HFpEF). Adipocyte free fatty acid binding protein (a-FABP) has been shown to signal endothelial dysfunction through fatty acid toxicity, though its role in mediating ventricular-arterial dysfunction remains unclear. We prospectively examined the associations of a-FABP with central arterial pressure using non-invasive applanation tonometry (SphygmoCor) and cardiac structure/function (i.e., tissue Doppler imaging [TDI] and global longitudinal myocardial strain [GLS]) in patients with cardiometabolic (CM) risk (n = 150) and HFpEF (n = 50), with healthy volunteers (n = 49) serving as a control. We observed a graded increase of a-FABP across the healthy controls, CM individuals, and HFpEF groups (all paired p

BackgroundEpicardial adipose tissue (EAT) as a marker of metabolic disorders has been shown to be closely associated with a variety of unfavorable cardiovascular events and cardiac arrhythmias. Data on regional-specific visceral adiposity outside the heart and its modulation on autonomic dysfunction, particularly heart rate recovery after exercise, remain obscure.MethodsWe studied 156 consecutive subjects (mean age: 49.3 ± 8.0 years) who underwent annual health surveys and completed treadmill tests. Multi-detector computed tomography-based visceral adiposity, including EAT and peri-aortic fat (PAF) tissue, was quantified using dedicated software (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). We further correlated EAT and PAF with blood pressure and heart rate (HR) recovery information from an exercise treadmill test. Metabolic abnormalities were scored by anthropometrics in combination with biochemical data.ResultsIncreased EAT and PAF were both associated with a smaller reduction in systolic blood pressure during the hyperventilation stage before exercise compared to supine status (β-coefficient (coef.): −0.19 and −0.23, respectively, both p < 0.05). Both visceral adipose tissue mediated an inverted relationship with heart rate recovery at 3 (EAT: β-coef.: −0.3; PAF: β-coef.: −0.36) and 6 min (EAT: β-coef.: −0.32; PAF: β-coef.: −0.34) after peak exercise, even after adjusting for baseline clinical variables and body fat composition (all p < 0.05).ConclusionExcessive visceral adiposity, whether proximal or distal to the heart, may modulate the autonomic response by lowering the rate of HR recovery from exercise after accounting for clinical metabolic index. Cardiac autonomic dysfunction may partly explain the increase in cardiovascular morbidity and mortality related to both visceral fats.

Background Heart failure with reduced ejection fraction (HFrEF) is a chronic disease with substantial mortality. Management of HFrEF has seen significant breakthrough after the launch of neprilysin inhibitor. The PARADIGM‐HF (Prospective Comparison of ARNI with ACEI to Determine Impacton Global Mortality and Morbidity in Heart Failure) trial showed that sacubitril/valsartan significantly reduces HFrEF mortality and the heart failure hospitalization rate. However, in patients with advanced kidney disease, who have the highest prevalence of heart failure, the efficacy and safety of sacubitril/valsartan remains uncertain. We aim to study the efficiency of sacubitril/valsartan in patients with end‐stage kidney disease. Methods and Results Heart function was screened by echocardiogram among all patients with end‐stage kidney disease in 2 hospitals. Patients with HFrEF received either sacubitril/valsartan or conventional treatment. Fifteen echocardiographic parameters were compared before and after treatment. After 1‐year sacubitril/valsartan treatment, parameters of systolic (left ventricular ejection fraction 31.3% to 45.1%, P

Abstract Background Cardiac abnormalities have been observed in patients with mucopolysaccharidosis type II (MPS II). The aim of this study was to investigate the cardiac features and natural progression of Taiwanese patients with MPS II, and evaluate the impact of enzyme replacement therapy (ERT) on cardiac structure and function. Methods The medical records and echocardiograms of 48 Taiwanese patients with MPS II (median age, 6.9 years; age range, 0.1–27.9 years) were reviewed. The relationships between age and each echocardiographic parameter were analyzed. Results The mean z-scores of left ventricular mass index (LVMI), interventricular septum diameter in diastole (IVSd), left ventricular posterior wall diameter in diastole (LVPWd), and aortic diameter were 1.10, 2.70, 0.95 and 1.91, respectively. Z scores > 2 were identified in 33%, 54%, 13%, and 46% for LVMI, IVSd, LVPWd, and aortic diameter, respectively. The most prevalent cardiac valve abnormality was mitral regurgitation (MR) (56%), followed by aortic regurgitation (AR) (33%). The severity of mitral stenosis (MS), MR, aortic stenosis (AS), AR, and the existence of valvular heart disease were all positively correlated with increasing age (p 0.05). Conclusions High prevalence rates of valvular heart disease and cardiac hypertrophy were observed in the MPS II patients in this study. The existence and severity of cardiac hypertrophy and valvular heart disease in these patients worsened with increasing age, reinforcing the concept of the progressive nature of this disease. ERT for MPS II appeared to be effective in stabilizing or reducing the progression of cardiac hypertrophy, but it only had a limited effect on valvulopathy.

BackgroundSurvivors of preterm birth are at risk of long-term cardiovascular consequences. The objective of this prospective observational study was to assess left heart function at preschool age in preterm children with very low birth weight (VLBW).MethodsWe recruited children aged 5–6 years from preterm infants and full-term children. All subjects underwent conventional echocardiography and speckle-tracking echocardiography. The results were compared between the preterm and term groups.ResultsEighty-seven VLBW preterm children and 29 term controls were included in the study. After adjusting for body surface area, the preterm group compared to the full-term group had significantly smaller left ventricular (LV) end-diastolic and end-systolic internal dimensions (31.2 vs. 33.5 mm, p = 0.048; and 20.0 vs. 21.6 mm, respectively; p = 0.024), lower LV end-diastolic and end-systolic volumes (38.8 vs. 46.3 mL, p = 0.024; and 12.8 vs. 15.6 mL, respectively; p = 0.008). Left atrial (LA) maximal and minimal volume were also significantly smaller in the preterm group (15.4 vs. 18.9 mL, p = 0.017; and 6.2 vs 7.5 mL, respectively; p = 0.018). LV global longitudinal strain (−21.4 vs. −23.2%, p < 0.0001) and systolic strain rate (−1.30 vs. −1.37 /s, p = 0.001) were significantly lower in the preterm group than in the term control group. LA longitudinal strain was decreased (43.9 vs. 52.8%, p < 0.0001) and left atrial stiffness index (0.17 vs. 0.14, p < 0.0001) was increased in preterm infants. However, all the measurements in both groups were within normal range.ConclusionsSubclinical changes of left heart structure and function were found in VLBW infants at preschool age. Additional long-term follow-ups of the cardiovascular outcomes are needed in this vulnerable population.

BackgroundDespite known sex differences in cardiac structure and function, little is known about how menopause and estrogen associate with atrioventricular mechanics and outcomes.ObjectiveTo study how, sex differences, loss of estrogen in menopause and duration of menopause, relate to atrioventricular mechanics and outcomes.MethodsAmong 4051 asymptomatic adults (49.8 ± 10.8 years, 35%women), left ventricular (LV) and left atrial (LA) mechanics were assessed using speckle-tracking.ResultsPost-menopausal (vs. pre-menopausal) women had similar LV ejection fraction but reduced GLS, reduced PALS, increased LA stiffness, higher LV sphericity and LV torsion (all p < 0.001). Multivariable analysis showed menopause to be associated with greater LV sphericity (0.02, 95%CI 0.01, 0.03), higher indexed LV mass (LVMi), lower mitral e’, lower LV GLS (0.37, 95%CI 0.04–0.70), higher LV torsion, larger LA volume, worse PALS (∼2.4-fold) and greater LA stiffness (0.028, 95%CI 0.01–0.05). Increasing years of menopause was associated with further reduction in GLS, markedly worse LA mechanics despite greater LV sphericity and higher torsion. Lower estradiol levels correlated with more impaired LV diastolic function, impaired LV GLS, greater LA stiffness, and increased LV sphericity and LV torsion (all p < 0.05). Approximately 5.5% (37/669) of post-menopausal women incident HF over 2.9 years of follow-up. Greater LV sphericity [adjusted hazard ratio (aHR) 1.04, 95%CI 1.00–1.07], impaired GLS (aHR 0.87, 95%CI 0.78–0.97), reduced peak left atrial longitudinal strain (PALS, aHR 0.94, 95%CI 0.90–0.99) and higher LA stiffness (aHR 10.5, 95%CI 1.69–64.6) were independently associated with the primary outcome of HF hospitalizations in post-menopause. Both PALS < 23% (aHR:1.32, 95%CI 1.01–3.49) and GLS < 16% (aHR:5.80, 95%CI 1.79–18.8) remained prognostic for the incidence of HF in post-menopausal women in dichotomous analyses, even after adjusting for confounders. Results were consistent with composite outcomes of HF hospitalizations and 1-year all-cause mortality as well.ConclusionMenopause was associated with greater LV/LA remodeling and reduced LV longitudinal and LA function in women. The cardiac functional deficit with menopause and lower estradiol levels, along with their independent prognostic value post-menopause, may elucidate sex differences in heart failure further.

BackgroundHeart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) commonly coexist with overlapping pathophysiology like left atrial (LA) remodeling, which might differ given different underlying mechanisms.ObjectivesWe sought to investigate the different patterns of LA wall remodeling in AF vs. HFpEF.MethodsWe compared LA wall characteristics including wall volume (LAWV), wall thickness (LAWT), and wall thickness heterogeneity (LAWT[SD]) and LA structure, function among the controls (without AF or HFpEF, n = 115), HFpEF alone (n = 59), AF alone (n = 37), and HFpEF+AF (n = 38) groups using multi-detector computed tomography and echocardiography.ResultsLA wall remodeling was most predominant and peak atrial longitudinal strain (PALS) was worst in HFpEF+AF patients as compared to the rest. Despite lower E/e' (9.8 ± 3.8 vs. 13.4 ± 6.4) yet comparable LA volume, LAWT and PALS in AF alone vs. HFpEF alone, LAWV [12.6 (11.6–15.3) vs. 12.0 (10.2–13.7); p = 0.01] and LAWT(SD) [0.68 (0.61–0.71) vs. 0.60 (0.56–0.65); p < 0.001] were significantly greater in AF alone vs. HFpEF alone even after multi-variate adjustment and propensity matching. After excluding the HFpEF+AF group, both LAWV and LAWT [SD] provided incremental values when added to PALS or LAVi (all p for net reclassification improvement

Abstract Aims This study aimed to investigate the functional correlate, clinical relevance, and prognostic implications of novel left ventricular (LV) deformations in patients with atrial fibrillation (AF). Methods and results LV deformational indices, including peak global longitudinal strain (GLS), systolic strain rates (SRs), and early diastolic strain rates (SRe) were measured in a large‐scale AF population. We related such measures to key clinical heart failure (HF) markers, conventional echocardiographic ventricular parameters, and clinical outcomes. Among 1483 subjects with newly diagnosed AF (mean age, 71.6 ± 12.4 years; 55.5% male), worsened GLS (mean, − 12.6 ± 3.9%) and strain rates (SRs and SRe: mean, − 0.86 ± 0.27 and 1.25 ± 0.41 1/s, respectively) by our three‐beat measures were independently correlated with higher C‐reactive protein, N‐terminal pro‐B‐type natriuretic peptide, higher E/e′, more impaired LV ejection fraction (LVEF − 14.7%) was common in our cohort (67.8%) despite an averaged preserved LVEF (58.4 ± 14.2%), with worse GLS and SRe being associated with higher composite HF re‐admissions/death during the 2.9 year follow‐up (inter‐quartile range, 1.6–4.1 years) in multivariate models incorporating key LV indices (LVEF, LV mass index, and E/e′) (all P

Abstract Aims Excessive visceral adiposity (VAT) plays an essential role in metabolic derangements with those close to heart further mediates myocardial homeostasis. The disparate biological links between region‐specific VAT and cardiometabolic profiles as mediators influencing atrial kinetics remain unexplored. Methods and results Among 1326 asymptomatic individuals, region‐specific VAT including peri‐aortic root fat (PARF) and total pericardial fat (PCF) of cardiac region, together with thoracic peri‐aortic adipose tissue (TAT), was assessed using multiple‐detector computed tomography. VAT measures were related to functional left atrial (LA) metrics assessed by speckle‐tracking algorithm and clinical outcomes of atrial fibrillation (AF) and heart failure (HF). Multivariate linear regression models incorporating body fat, metabolic syndrome, and E/TDI‐e' consistently demonstrated independent associations of larger PARF/PCF with peak atrial longitudinal systolic strain (PALS) reduction, higher LA stiffness, and worsened strain rate components; instead, TAT was independently associated with cardiometabolic profiles. PARF rather than PCF or TAT conferred independent prognostic values for incident AF/HF by multivariate Cox regression (adjusted hazard ratio: 1.56, 95% confidence interval: 1.17–2.08, P = 0.002) during a median of 1790 days (interquartile range: 25th to 75th: 1440–1927 days) of follow‐up, with subjects categorized into worst PALS and largest VAT tertiles demonstrating highest events (all log‐rank P

Abstract Aims We aimed to characterize ethnic differences in prevalence, clinical correlates, and outcomes of atrial fibrillation (AF) in heart failure (HF) with preserved and reduced ejection fraction (HFpEF and HFrEF) across Asia. Methods and results Among 5504 patients with HF prospectively recruited across 11 Asian regions using identical protocols in the Asian Sudden Cardiac Death in Heart Failure study (mean age 61 ± 13 years, 27% women, 83% HFrEF), 1383 (25%) had AF defined as a history of AF and/or AF/flutter on baseline electrocardiogram. Clinical correlates of AF were similar across ethnicities and included older age, prior stroke, higher NT‐proBNP, and larger left atria. Diabetes was associated with lower odds of AF in HFrEF [adjusted odds ratio (AOR) 0.79, 95% CI 0.66–0.95] and HFpEF (AOR 0.58, 95% CI 0.39–0.84) regardless of ethnicity. Compared with Chinese ethnicity, Japanese/Koreans had higher odds of AF in HFrEF (AOR 1.76, 95% CI 1.40–2.21), while Indians had lower odds in HFrEF (AOR 0.18, 95% CI 0.13–0.24) and HFpEF (AOR 0.28, 95% CI 0.16–0.49) even after adjusting for clinical covariates. Interaction between ethnicity and region was observed among Indians, with Southeast Asian Indians having higher odds of AF (AOR 3.01, 95% CI 1.60–5.67) compared with South Asian Indians. AF was associated with poorer quality of life and increased risk of 1 year all‐cause mortality or HF hospitalisation (adjusted hazard ratio 1.39, 95% CI 1.18–1.63) regardless of ethnicity. Conclusions Among patients with HF across Asia, clinical correlates and adverse outcomes associated with AF are similar across ethnicities; however, there are striking ethnic variations in the prevalence of AF that are not accounted for by known risk factors.

Abstract Aims We aimed to investigate the functional alterations, diagnostic utilization, and prognostic implication of carotid arterial deformations in subjects with cardiovascular risk factors and heart failure (HF) with preserved ejection fraction (HFpEF). Methods and results Among 251 prospectively participants (mean age 66.0 ± 9.8 years, 65.7% female) in a single centre between December 2011 and September 2014, carotid artery deformations including circumferential strain (CCS)/strain rate and radial strain were analysed by two‐dimensional speckle tracking. We further related these carotid artery deformation indices to HF biomarkers and cardiac structure and function by echocardiography and explored their prognostic values. Significant reductions of CCS, circumferential strain rate, and circumferential radial strain were observed across control (n = 52), high risk (n = 147), and HFpEF (n = 52) (trend P ≤ 0.001). Aging, hypertension, HFpEF, and higher pulse rate showed independent associations with reduced CCS by stepwise multivariate regressions (all P

Purpose: This study evaluated the diagnostic values of the extent of lung injury manifested in non-contrast enhanced CT (NCCT) images, the inflammatory and immunological biomarkers C-reactive protein (CRP) and lymphocyte for detecting acute cardiac injury (ACI) in patients with COVID-19. The correlations between the NCCT-derived parameters and arterial blood oxygen level were also investigated. Methods: NCCT lung images and blood tests were obtained in 143 patients with COVID-19 in approximately two weeks after symptom onset, and arterial blood gas measurement was also acquired in 113 (79%) patients. The diagnostic values of normal, moderately and severely abnormal lung parenchyma volume relative to the whole lungs (RVNP, RVMAP, RVSAP, respectively) measured from NCCT images for detecting the heart injury confirmed with high-sensitivity troponin I assay was determined. Results: RVNP, RVMAP and RVSAP exhibited similar accuracy for detecting ACI in COVID-19 patients. RVNP was significantly lower while both RVMAP and RVSAP were significantly higher in the patients with ACI. All of the NCCT-derived parameters exhibited poor linear and non-linear correlations with PaO2 and SaO2. The patients with ACI had a significantly higher CRP level but a lower lymphocyte level compared to the patients without ACI. Combining one of these two biomarkers with any of the three NCCT-derived parameter further improved the accuracy for predicting ACI in patients with COVID-19. Conclusion: The NCCT-delineated normal and abnormal lung parenchmyma tissues were statistically significant predictors of ACI in patients with COVID-19, but both exhibited poor correlations with the arterial blood oxygen level. The incremental diagnostic values of lymphocyte and CRP suggested viral infection and inflammation were closely related to the heart injury during the acute stage of COVID-19.

Background Visceral adipose tissue is assumed to be an important indicator for insulin resistance and diabetes beyond overweight/obesity. We hypothesized that region‐specific visceral adipose tissue may regulate differential biological effects for new‐onset diabetes regardless of overall obesity. Methods and Results We quantified various visceral adipose tissue measures, including epicardial adipose tissue, paracardial adipose tissue, interatrial fat, periaortic fat, and thoracic aortic adipose tissue in 1039 consecutive asymptomatic participants who underwent multidetector computed tomography. We explored the associations of visceral adipose tissue with baseline dysglycemic indices and new‐onset diabetes. Epicardial adipose tissue, paracardial adipose tissue, interatrial fat, periaortic fat, and thoracic aortic adipose tissue were differentially and independently associated with dysglycemic indices (fasting glucose, postprandial glucose, HbA1c, and homeostasis model assessment of insulin resistance) beyond anthropometric measures. The superimposition of interatrial fat and thoracic aortic adipose tissue on age, sex, body mass index, and baseline homeostasis model assessment of insulin resistance expanded the likelihood of baseline diabetes (from 67.2 to 86.0 and 64.4 to 70.8, P for ∆ ꭕ2:

Background Data on rehospitalizations for heart failure (HF) in Asia are scarce. We sought to determine the burden and predictors of HF (first and recurrent) rehospitalizations and all‐cause mortality in patients with HF and preserved versus reduced ejection fraction (preserved EF, ≥50%; reduced EF,

[This corrects the article DOI: 10.1371/journal.pmed.1003661.].

Objective: Previous studies have discussed acute myocardial infarction (AMI) patients without chest pain, but have not focused on non-ST-elevation myocardial infarction (NSTEMI). Materials and methods: This 1-year study investigated whether chest pain presence relates to demographics, risk factors, and outcomes in NSTEMI patients. We retrospectively reviewed 194 patients, 73 without chest pain vs. 121 with chest pain, and compared the differences between clinical presentations, risk factors, medical management, and outcomes of these two groups. Results: Compared to patients with chest pain, patients without chest pain were significantly older, had lower SBP, higher HR, more cerebrovascular disease, less ischemic heart disease, higher delay to ED (emergency department) visit, lower ED medication prescriptions, lower percutaneous cardiac intervention, and higher in-hospital and one-year mortality rate. In a multivariate logistic regression, the adjusted odds ratios (OR) of patients without chest pain were 4.38 for the elderly, 0.99 for every 1 mmHg increase in SBP, 1.02 for every beat/min HR increase, 0.37 for those with ischemic heart disease, and 5.09 for those with cerebrovascular disease. The adjusted OR of in-hospital mortality were 3.09 for patients without chest pain, 0.32 for those with hypertension, 0.32 for smokers, 3.98 for those with shock, and 0.16 for those with percutaneous cardiac intervention. Finally, the only significantly adjusted OR of one-year mortality was 5.37 for patients without chest pain. Conclusion: NSTEMI patients without chest pain were significantly older, had lower SBP, more tachycardia, more cerebrovascular disease, but less ischemic heart disease. They also experienced higher in-hospital and one-year mortality rates. Keywords: Non-ST-Elevation myocardial infarction (NSTEMI), Without chest-pain, Chest pain, Mortality

Abstract Aims This study aimed to evaluate the prognostic significance of nutritional status in post‐discharge Asians with heart failure with preserved ejection fraction (HFpEF). Methods and results We examined the prognostic implications of body mass index (BMI) and nutritional markers among consecutive patients hospitalized for HFpEF. Nutritional metrics were estimated by serum albumin (SA), prognostic nutritional index (PNI), Controlling Nutritional Status (CONUT) score, and geriatric nutritional risk index. Among 1120 patients (mean age: 77.2 ± 12.6 years, 39.4% men), mean SA levels, PNI, CONUT scores, and geriatric nutritional risk index were 3.3 ± 0.6 g/dL, 40.2 ± 8.7, 5.5 ± 2.1, and 95.9 ± 14.5, respectively. Lean body size, higher white blood cell counts and C‐reactive protein levels, anaemia, and lack of angiotensin blocker use were independently associated with malnutrition (defined by SA < 3.5 g/dL). Higher SA levels [hazard ratio (HR): 0.67 (95% confidence interval, CI: 0.53–0.85)], higher PNI [HR: 0.97 (95% CI: 0.95–0.99)], and higher geriatric nutritional risk index [HR: 0.98 (95% CI: 0.97–0.99)] (all P < 0.05) were all associated with longer survival, with higher CONUT score [HR: 1.08 (95% CI: 1.02–1.13)] exhibited higher mortality in Cox regression models and with higher SA levels/PNI but not BMI further contributing to the reduced rate of re‐hospitalization (both P < 0.05). Categorizing BMI (25 kg/m2 as cut‐off) and nutritional status showed significantly higher mortality rates among patients with lower BMI/malnutrition than among those with BMI/better nutrition (SA level, PNI, and CONUT score, all P < 0.01). Restricted cubic spline regression revealed a marked survival benefit of better nutrition with increasing BMI (adjusted Pinteraction for both SA level and PNI:

Abstract Aims Left atrial (LA) remodelling is an important predictor of cardiovascular events of heart failure (HF) and atrial fibrillation. Data regarding diagnostic value of LA remodelling on diastolic dysfunction (DD) and preclinical HF remain largely unexplored. Methods and results We assessed LA dimension (LAD) in 8368 consecutive asymptomatic Asians (mean age: 49.7, 38.9% women) and related such measure to updated American Society of Echocardiography (ASE) DD criteria and newly revised N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) cut‐off (≥125 pg/mL) and HF with preserved ejection fraction criteria incorporating NT‐proBNP and echocardiography parameters by the European Society of Cardiology (ESC). LAD and indexed LAD (LADi) were both inversely correlated with myocardial relaxation e′ and positively associated with indexed LA volume, left ventricular E/e′, and tricuspid regurgitation velocity (all P 34 mL/m2; positive predictive value: 96%) and well‐discriminated ESC‐recommended NT‐proBNP (≥125 pg/mL, LAD: 37 mm) for HF. Conclusions Single utilization of atrial remodelling is highly useful for ruling out presence of DD and provides practical threshold for identifying preclinical HF based on most updated guidelines.

Introduction: Ectopic fat deposition may contribute to chronic inflammation in people with HIV (PWH). To inform future mechanistic studies of metabolic risk in this population, we sought to determine which fat measures relate more strongly to inflammation and whether the fat-inflammation relationship is modified by sex or HIV status. Methods: We conducted a cross-sectional study of 105 PWH and 20 age- and sex-matched HIV-negative controls. Interleukin-6 (IL-6) and high-sensitivity C reactive protein (hs-CRP) levels were measured from plasma. Pericardial fat (PCF) and thoracic periaortic adipose tissue (TAT) volumes and peri-right coronary artery (RCA), left atrium (LA) roof and liver densities were measured from cardiac CT scans. Unadjusted and multivariate adjusted linear regression models were used to determine the relationship between ectopic fat measures and inflammation biomarkers. Results: Forty subjects had BMI 30. Systolic blood pressure and insulin resistance increased with BMI. Subjects with higher BMI had higher CD4+ count. In models adjusted for demographics, HIV status and metabolic risk factors, BMI was positively associated with IL-6 and hs-CRP. Ectopic PCF and TAT volumes were positively associated with IL-6 and hs-CRP; however, these relationships were somewhat attenuated in adjusted models. LA roof (but not peri-RCA) fat radiodensity was inversely associated with hs-CRP in fully adjusted models and the association with IL-6 was borderline statistically significant. IL-6 was more strongly associated with BMI and LA roof density in women than in men (p for interaction=0.05). Conclusions: Among PWH on antiretroviral therapy, higher BMI and excessive visceral fat burden were associated with circulating markers of systemic inflammation, and this relationship appears to be stronger in women compared to men.

Abstract Background Mucopolysaccharidosis type III (MPS III), or Sanfilippo syndrome, is caused by a deficiency in one of the four enzymes involved in the lysosomal degradation of heparan sulfate. Cardiac abnormalities have been observed in patients with all types of MPS except MPS IX, however few studies have focused on cardiac alterations in patients with MPS III. Methods We reviewed medical records, echocardiograms, and electrocardiograms of 26 Taiwanese patients with MPS III (five with IIIA, 20 with IIIB, and one with IIIC; 14 males and 12 females; median age, 7.4 years; age range, 1.8–26.5 years). The relationships between age and each echocardiographic parameter were analyzed. Results Echocardiographic examinations (n = 26) revealed that 10 patients (38%) had valvular heart disease. Four (15%) and eight (31%) patients had valvular stenosis or regurgitation, respectively. The most prevalent cardiac valve abnormality was mitral regurgitation (31%), followed by aortic regurgitation (19%). However, most of the cases of valvular heart disease were mild. Three (12%), five (19%) and five (19%) patients had mitral valve prolapse, a thickened interventricular septum, and asymmetric septal hypertrophy, respectively. The severity of aortic regurgitation and the existence of valvular heart disease, aortic valve abnormalities and valvular stenosis were all positively correlated with increasing age (p 2 were identified in 0, 38, 8, and 27% of left ventricular mass index, interventricular septal end-diastolic dimension, left ventricular posterior wall end-diastolic dimension, and aortic diameter, respectively. Electrocardiograms in 11 patients revealed the presence of sinus arrhythmia (n = 3), sinus bradycardia (n = 2), and sinus tachycardia (n = 1). Six patients with MPS IIIB had follow-up echocardiographic data at 1.9–18.1 years to compare with the baseline data, which showed some patients had increased thickness of the interventricular septum, as well as more patients had valvular abnormalities at follow-up. Conclusions Cardiac involvement in MPS III is less common and milder compared with other types of MPS. The existence of valvular heart disease, aortic valve abnormalities and valvular stenosis in the patients worsened with increasing age, reinforcing the concept of the progressive nature of this disease.

Abstract Background The Slug-E-cadherin axis plays a critical role in non-small-cell lung cancers (NSCLCs) where aberrant upregulation of Slug promotes cancer metastasis. Now, the post-translational modifications of Slug and their regulation mechanisms still remain unclear in lung cancer. Hence, exploring the protein linkage map of Slug is of great interest for investigating the scenario of how Slug protein is regulated in lung cancer metastasis. Methods The Slug associated proteins, Ubc9 and SUMO-1, were identified using yeast two-hybrid screening; and in vitro SUMOylation assays combined with immunoprecipitation and immunoblotting were performed to explore the detail events and regulations of Slug SUMOylation. The functional effects of SUMOylation on Slug proteins were examined by EMSA, reporter assay, ChIP assay, RT-PCR, migration and invasion assays in vitro, tail vein metastatic analysis in vivo, and also evaluated the association with clinical outcome of NSCLC patients. Results Slug protein could interact with Ubc9 and SUMO-1 and be SUMOylated in cells. Amino acids 130–212 and 33–129 of Slug are responsible for its binding to Ubc9 and protein inhibitor of activated STAT (PIAS)y, respectively. SUMOylation could enhance the transcriptional repression activity of Slug via recruiting more HDAC1, resulting in reduced expression of downstream Slug target genes and enhanced lung cancer metastasis. In addition, hypoxia could increase Slug SUMOylation through attenuating the interactions of Slug with SENP1 and SENP2. Finally, high expression Slug and Ubc9 levels were associated with poor overall survival among NSCLC patients. Conclusions Ubc9/PIASy-mediated Slug SUMOylation and subsequent HDAC1 recruitment may play a crucial role in hypoxia-induced lung cancer progression, and these processes may serve as therapeutic targets for NSCLC.

Background: Plaque in carotid arteries (CAs) is a major factor of systemic atherosclerosis and cardiovascular disease (CVD). The left and right CAs have different anatomic and geometric features and may influence the predictability of CVD. However, the site- and segment-specific prevalence of carotid plaques (CP) and study on severity of carotid atherosclerosis with CVD risks was very limited. Methods: We enrolled 1539 healthy residents aged 40-to-74 years from two northern districts in Taiwan. All volunteers received high resolution B-mode carotid ultrasound scans and CVD risk factors evaluations. Results: The prevalence rate of extracranial CP was 21.9% in females and 33.8% in males. Carotid bifurcation is the most affected segment. As compared with the right CAs, the age-sex-adjusted matched odds ratio of having plaques in the left CAs was 1.32 (95% confidence interval = 1.02–1.73). The proportions of subjects had a total plaque number≥2, maximum stenosis≥30%, and plaque score≥3 were 8.9, 10.3, and 7.2%, respectively, in females and were 17.7, 17.2, and 15.1%, respectively, in males. Among subjects with moderate and severe carotid atherosclerosis, the mean ± SD of estimated 10-year CVD risk was 19.1 ± 14.6% and more than 65% of them need intensive blood pressure, lipids, or sugar controls. Conclusion: We found that bifurcation was the most prevalent segment, and left CAs was more likely to form plaque than right CAs. The major CVD risk factors were highly prevalent and the estimated CVD risks were high in subjects with more advanced carotid atherosclerosis. The study provides further direction for CVD prevention and treatment. Keywords: Carotid plaque, Segment-specific, Cardiovascular risk factors, Community-based study

BackgroundObesity, a known risk factor for cardiovascular disease and heart failure (HF), is associated with adverse cardiac remodeling in the general population. Little is known about how nutritional status modifies the relationship between obesity and outcomes. We aimed to investigate the association of obesity and nutritional status with clinical characteristics, echocardiographic changes, and clinical outcomes in the general community.Methods and findingsWe examined 5,300 consecutive asymptomatic Asian participants who were prospectively recruited in a cardiovascular health screening program (mean age 49.6 ± 11.4 years, 64.8% male) between June 2009 to December 2012. Clinical and echocardiographic characteristics were described in participants, stratified by combined subgroups of obesity and nutritional status. Obesity was indexed by body mass index (BMI) (low, ≤25 kg/m2 [lean]; high, >25 kg/m2 [obese]) (WHO-recommended Asian cutoffs). Nutritional status was defined primarily by serum albumin (SA) concentration (low, ConclusionsIn our cohort study among asymptomatic community-based adults in Taiwan, we found that obese individuals with poor nutritional status have the highest comorbidity burden, the most adverse cardiac remodeling, and the least favorable composite outcome.

Background Biomarkers of myocardial stress and fibrosis are elevated in people living with HIV and are associated with cardiac dysfunction. It is unknown whether sex influences these markers of heart failure risk in sub‐Saharan Africa, where HIV burden is high and where the vast majority of women with HIV live. Methods and Results Echocardiograms and 6 plasma biomarkers (suppression of tumorigenicity‐2, growth differentiation factor 15, galectin 3, soluble fms‐like tyrosine kinase‐1, NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide], and cystatin C) were obtained from 100 people living with HIV on antiretroviral therapy and 100 HIV‐negative controls in Uganda. All participants were ≥45 years old with ≥1 major cardiovascular risk factor. Multivariable linear and logistic regression models were used to assess associations between biomarkers, echocardiographic variables, HIV status, and sex, and to assess whether sex modified these associations. Overall, mean age was 56 years and 62% were women. Suppression of tumorigenicity‐2 was higher in men versus women (P

Non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease share several cardiometabolic risk factors. Excessive visceral fat can manifest as ectopic fat depots over vital organs, such as the heart and liver. This study assessed the associations of NAFLD and liver fibrosis with cardiac structural and functional disturbances. We assessed 2161 participants using ultrasound, and categorized them as per the NAFLD Fibrosis Score into three groups: (1) non-fatty liver; (2) fatty liver with low fibrosis score; and (3) fatty liver with high fibrosis score. Epicardial fat volume (EFV) was measured through multidetector computed tomography. All participants underwent echocardiographic study, including tissue Doppler-based E/e’ ratio and speckle tracking-based left ventricular global longitudinal strain, peak atrial longitudinal strain (PALS), and atrial longitudinal strain rates during systolic, early and late-diastolic phases (ALSRsyst, ALSRearly. ALSRlate). Larger EFV, decreased e’ velocity, PALS, ALSRsyst, and ALSRearly, along with elevated E/e’ ratio, were seen in all groups, especially in those with high fibrosis scores. After multivariate adjustment for traditional risk factors and EFV, fibrosis scores remained significantly associated with elevated E/e’ ratio, LA stiffness, and decreased PALS (β: 0.06, 1.4, −0.01, all p < 0.05). Thus, NAFLD is associated with LV diastolic dysfunction and subclinical changes in LA contractile mechanics.

Smoking is known as a powerful predictor of pathological coronary atherosclerosis. Thoracic aortic calcification (TAC), an alternative marker for pathological atherosclerosis, has also been shown to be associated unfavorable cardiovascular outcomes. We aimed to investigate the dose-response relationship between cigarette use and calcification burden in subjects free from clinical symptoms. Among 3109 patients enrolled in this analysis, we categorized study participants according to smoking exposure pattern as: non-smokers, ex-smokers and current smokers. Smoking dose (cigarette/day), duration (years) and pack-years were semi-quantified as smoking dose exposure variables. Thoracic aortic calcification burden (including TAC score, plaque volume and plaque density) were determined and related to smoking dose and pattern information. TAC burdens (including TAC score, plaque volume and density) were highest in current smoker compared to non-smoker group, with ex-smoker showing TAC burdens in-between (all ANOVA p 10 cigarettes/day) and the long-duration (> 3 years) smokers, even after adjusting for baseline demographic differences (all p

Hyperuricemia (HU) is a marker for heart failure. There are relatively few data in the Asian population regarding the effects of hyperuricemia and gouty disorders on cardiac remodeling and diastolic dysfunction (DD), an intermediate stage in the development of heart failure. We consecutively recruited asymptomatic Asian individuals to undergo cardiovascular surveys. We categorized them into Non-HU, HU, and Gout groups. We measured cardiac structure and indices for diastolic function, including tissue Doppler (TDI)-derived LV e' and E/e'. Among 5525 participants, 1568 had HU and 347 had gout. The presence of gout and higher uric acid levels (SUA) ( = 10 mg/dL) were associated with greater LV wall thickness, greater LV mass/volumes, larger LA volume, lower LV e' and higher E/e'. Higher SUA was associated with greater LV mass index (adjusted coefficient: 0.37), greater mass/volume ratio (adjusted coefficient: 0.01) and larger LA volume index (adjusted coefficient: 0.39, all p