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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.

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

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, alirocumab and evolocumab, are currently approved for clinical use by Taiwan National Health Insurance (NHI) in patients who had a recent atherosclerotic cardiovascular disease with persistent LDL-C levels >135 mg/dL despite high-intensity statin (HIS) or maximally tolerated statin in combination with ezetimibe treatment. Since January 2020 to July 2020, total of 10 patients who had received coronary revascularization received NHI-approved alirocumab or evolocumab in our institution. The mean reduction of LDL-C following PCSK9 inhibitors treatment at 6-month and 12-month were respectively 62.5% and 60.2%. The patients in our study were younger, had more frequently received HIS/ezetimibe, and had higher baseline LDL-C levels with a greater LDL-C reduction following PCSK9 inhibitors treatment compared with those patients in previously studies. Our findings highlight that the NHI's regulation of PCSK9 inhibitors application should be re-evaluation to increase the use of NHI-approved PCSK9 inhibitors in high-risk patients.

Background/Purpose: Pharmacogenetics is a potential driver of the “East Asian paradox,” in which East Asian acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy (DAPT) with clopidogrel following percutaneous coronary intervention (PCI) demonstrate higher levels of platelet reactivity on treatment than Western patients, yet have lower ischemic risk and higher bleeding risk at comparable doses. However, the impact of pharmacogenetics, particularly regarding CYP2C19 genotype, on the pharmacodynamics of P2Y12 inhibitors has not been extensively studied in Taiwanese ACS patients as yet. Methods: CYP2C19 genotyping and pharmacogenetic analysis was conducted on 102 subjects from the Switch Study, a multicenter, single-arm, open-label intervention study that examined the effects on platelet activity and clinical outcomes of switching from clopidogrel (75 mg daily) to low-dose prasugrel (3.75 mg daily) for maintenance DAPT after PCI in 203 Taiwanese ACS patients. Results: Genotyping results revealed that 43.1% were CYP2C19 extensive metabolizers (EM), while 56.9% were reduced metabolizers (RM). After switching to prasugrel, mean P2Y12 reaction units (PRU) values were significantly reduced in both EM and RM populations, while the proportion of high on-treatment platelet reactivity (HPR) patients significantly declined in RM patients. No increase in bleeding risk after switching was observed during follow-up. Multivariate analysis indicated that for RM patients, low estimated glomerular filtration rate (eGFR) and low hemoglobin were associated with greater HPR risk on clopidogrel, but not after switching to prasugrel. Conclusion: Switching to low-dose prasugrel from clopidogrel reduced mean PRU levels and proportion of HPR patients, with more significant reduction in RM patients.

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

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 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

Abstract The therapeutic effects of ultrasonic microbubble transfection (UMT)-based vascular endothelial growth factor 165 (VEGF165) gene delivery on young and senescent endothelial progenitor cells (EPCs) were investigated. By UMT, plasmid DNA (pDNA) can be delivered into both young EPCs and senescent EPCs. In the UMT groups, higher pDNA-derived protein expression was found in senescent EPCs than in young EPCs. Consistent with this finding, a higher intracellular level of pDNA copy number was detected in senescent EPCs, with a peak at the 2-h time point post UMT. Ultrasonic microbubble delivery with or without VEGF improved the angiogenic properties, including the proliferation and/or migration activities, of senescent EPCs. Supernatants from young and senescent EPCs subjected to UMT-mediated VEGF transfection enhanced the proliferation and migration of human aortic endothelial cells (HAECs), and the supernatant of senescent EPCs enhanced proliferation more strongly than the supernatant from young EPCs. In the UMT groups, the stronger enhancing effect of the supernatant from senescent cells on HAEC proliferation was consistent with the higher intracellular VEGF pDNA copy number and level of protein production per cell in the supernatant from senescent cells in comparison to the supernatant from young EPCs. Given that limitations for cell therapies are the inadequate number of transplanted cells and/or insufficient cell angiogenesis, these findings provide a foundation for enhancing the therapeutic angiogenic effect of cell therapy with senescent EPCs in ischaemic cardiovascular diseases.

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.

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 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

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:

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:

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.

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.

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.

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

Background: Left ventricular noncompaction cardiomyopathy (LVNC) is a primary genetic cardiomyopathy with morphologically unique characteristics, including loose “spongy” meshwork. Subjects carrying these disorders were typically presented with triad of heart failure, cardiac arrhythmias, and consequences of mural thrombi formation. The clinical and echocardiographic features regarding LVNC, however, are not widely known. Methods: A retrospective survey involving 11 patients who fulfilled echocardiographic criteria for LVNC defined by Jenni et al. was conducted at MacKay Memorial Hospital from January 2009 to March 2017. Parameters assessed by echocardiography and clinical data were further analyzed. Results: Significantly depressed left ventricular systolic function assessed by echocardiography was noticed in a majority of our adult study cases. Conclusion: Considering the fatal complications LVNC may lead to, it is essential for clinical cardiologists to early identify suspicious individuals, and the establishment of definitive criteria and early treatment is essential.

Aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism is a common genetic variant in Asians that is responsible for defective toxic aldehyde and lipid peroxidation metabolism after alcohol consumption. The extent to which low alcohol consumption may cause atrial substrates to trigger atrial fibrillation (AF) development in users with ALDH2 variants remains to be determined. We prospectively enrolled 249 ethnic Asians, including 56 non-drinkers and 193 habitual drinkers (135 (70%) as ALDH2 wild-type: GG, rs671; 58 (30%) as ALDH2 variants: G/A or A/A, rs671). Novel left atrial (LA) mechanical substrates with dynamic characteristics were assessed using a speckle-tracking algorithm and correlated to daily alcohol consumption and ALDH2 genotypes. Despite modest and comparable alcohol consumption by the habitual alcohol users (14.3 [8.3~28.6] and 12.3 [6.3~30.7] g/day for those without and with ALDH2 polymorphism, p = 0.31), there was a substantial and graded increase in the 4-HNE adduct and prolonged PR, and a reduction in novel LA mechanical parameters (including peak atrial longitudinal strain (PALS) and phasic strain rates (reservoir, conduit, and booster pump functions), p < 0.05), rather than an LA emptying fraction (LAEF) or LA volume index across non-drinkers, and in habitual drinkers without and with ALDH2 polymorphism (all p < 0.05). The presence of ALDH2 polymorphism worsened the association between increasing daily alcohol dose and LAEF, PALS, and phasic reservoir and booster functions (all Pinteraction: p = 0.001). Impaired LA booster function further independently helped to predict AF after consideration of the CHARGE-AF score (adjusted 1.68 (95% CI: 1.06–2.67), p = 0.028, per 1 z-score increment). Habitual modest alcohol consumption led to mechanical LA substrate formation in an ethnic Asian population, which was more pronounced in subjects harboring ALDH2 variants. Impaired LA booster functions may serve as a useful predictor of AF in such populations.

In Taiwan, the prevalence of hyperlipidemia increased due to lifestyle and dietary habit changes. Low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) are all significant predicting factors of coronary artery disease in Taiwan. We recognized that lipid control is especially important in patients with existed atherosclerotic cardiovascular diseases (ASCVD), including coronary artery disease (CAD), ischemic stroke and peripheral arterial disease (PAD). Because the risk of ASCVD is high in patients with diabetes mellitus (DM), chronic kidney disease (CKD) and familial hypercholesterolemia (FH), lipid control is also necessary in these patients. Lifestyle modification is the first step to control lipid. Weight reduction, regular physical exercise and limitation of alcohol intake all reduce triglyceride (TG) levels. Lipid-lowering drugs include HMG-CoA reductase inhibitors (statins), cholesterol absorption inhibitors (ezetimibe), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, nicotinic acids (niacin), fibric acids derivatives (fibrates), and long-chain omega-3 fatty acids. Statin is usually the first line therapy. Combination therapy with statin and other lipid-lowering agents may be considered in some clinical settings. For patients with acute coronary syndrome (ACS) and stable CAD, LDL-C < 70 mg/dL is the major target. A lower target of LDL-C 40 in men and >50 mg/dL in women in DM. LDL-C increased CV risk in patients with CKD. In adults with glomerular filtration rate (GFR) < 60 mL/min/1.73m2 without chronic dialysis (CKD stage 3–5), statin therapy should be initiated if LDL-C ≥ 100 mg/dL. Ezetimibe can be added to statin to consolidate the CV protection in CKD patients. Mutations in LDL receptor, apolipoprotein B and PCSK9 genes are the common causes of FH. Diagnosis of FH usually depends on family history, clinical history of premature CAD, physical findings of xanthoma or corneal arcus and high levels of LDL-C. In addition to conventional lipid lowering therapies, adjunctive treatment with mipomersen, lomitapide, or PCSK9 inhibitors become necessary to further reduce LDL-C in patients with FH. Overall, these recommendations are to help the health care professionals in Taiwan to treat hyperlipidemia with current scientific evidences. We hope the prescription rate of lipid lowering drugs and control rate of hyperlipidemia in high risk patients could be increased by implementation of the clinical guidelines. The major purpose is to improve clinical outcomes of these high risk patients through the control of hyperlipidemia.

Epicardial adipose tissue (EAT) as a source of pro-inflammatory cytokines tightly linked to metabolic abnormalities. Data regarding the associations of EAT with adipocyte fatty acid-binding protein (A-FABP), a cytokine implicated in the cardiometabolic syndrome, might play an important part in mediating the association between EAT and cardiac structure/function in preserved ejection fraction heart failure (HFpEF). We conducted a prospective cohort study comprising 252 prospectively enrolled study participants classified as healthy (n = 40), high-risk (n = 161), or HFpEF (n = 51). EAT was assessed using echocardiography and compared between the three groups and related to A-FABP, cardiac structural/functional assessment utilizing myocardial deformations (strain/strain rates) and HF outcomes. EAT thickness was highest in participants with HFpEF (9.7 ± 1.7 mm) and those at high-risk (8.2 ± 1.5 mm) and lowest in healthy controls (6.4 ± 1.9 mm, p < 0.001). Higher EAT correlated with the presence of cardiometabolic syndrome, diabetes and renal insufficiency independent of BMI and waist circumference (pinteraction for all > 0.1), and was associated with reduced LV global longitudinal strain (GLS) and LV mass-independent systolic/diastolic strain rates (SRs/SRe) (all p < 0.05). Higher A-FABP levels were associated with greater EAT thickness (pinteraction > 0.1). Importantly, in the combined control cohort, A-FABP levels mediated the association between EAT and new onset HF. Excessive EAT is independently associated with the metabolic syndrome, renal insufficiency, and higher A-FABP levels. The association between EAT and new onset HF is mediated by A-FABP, suggesting a metabolic link between EAT and HF.

Obesity has been conceptualized as a highly heterogeneous condition. We aim to investigate chamber-specific effects of obesity on the heart and relevant outcomes. A total of 2944 symptom-free individuals (age: 47.5 ± 10.0 years), free of known cardiovascular diseases were classified into four categories based on body mass index (BMI) (as normal-weight (NW) vs. overweight/obese (O)) and metabolic status (metabolically-healthy (MH) vs. unhealthy (MU)). Epicardial adipose thickness (EAT) using echocardiography method. Speckle-tracking based atrio-ventricular (LA/LV) deformations including global longitudinal strain (GLS) and peak atrial longitudinal strain (PALS) were also analyzed. MUNW had higher cardiometabolic risks and more impaired diastolic and GLS/PALS than MHNW phenotype. Both MHO and MUO phenotypes exhibited worst atrial functions. Greater EAT was independently associated with worse GLS and PALS after correcting for various anthropometrics, LV mass and LA volume, respectively, with unfavorable LA effects from EAT being more pronounced in the NW phenotypes (both p interactions < 0.05). During a median follow-up period of 5.3 years, BMI/EAT improved the reclassification for atrial fibrillation (AF) incidence (p for net reclassification improvement < 0.05) mainly in the NW phenotypes (p interaction < 0.001). Categorization of clinical obesity phenotypes based on excessive visceral adiposity likely provides increment prognostic impacts on atrial dysfunction, particularly in non-obese phenotypes.

The debate regarding the actual cardiovascular burden in metabolically healthy obese or metabolically unhealthy non-obesity individuals is ongoing. Accumulating data have suggested a unique pathophysiological role of pro-inflammatory cytokines in mediating metabolic and cardiovascular disorders by dysregulated visceral adiposity. To compare the burden of visceral adiposity, the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and the prevalent atherosclerotic burden in metabolically healthy obese (MHO) or metabolically unhealthy (MU) populations, were compared to those of metabolically healthy non-obesity subjects (MHNO). Coronary artery calcification score (CACS) and visceral fat, including pericardial fat (PCF)/thoracic peri-aortic fat (TAT), were quantified in 2846 asymptomatic subjects using a CT dataset. A cross-sectional analysis comparing CACS, inflammatory marker hs-CRP, and visceral fat burden among four obesity phenotypes (MHNO, metabolically unhealthy non-obesity (MUNO), MHO, and metabolically unhealthy obese (MUO)) was performed. Both MUNO and MUO demonstrated significantly higher hs-CRP and greater CACS than MHNO/MHO (adjusted coefficient: 25.46, 95% confidence interval (CI): 5.29–45.63; 43.55, 95% CI: 23.38–63.73 for MUNO and MUO (MHNO as reference); both p < 0.05). Visceral fat (PCF/TAT) was an independent determinant of MU and was similarly higher in the MUNO/MHO groups than in the MHNO group, with the MUO group having the largest amount. PCF/TAT, obesity, and MU remained significantly associated with higher CACS even after adjustment, with larger PCF/TAT modified effects for MU and diabetes in CACS (both pinteraction < 0.05). MU tightly linked to excessive visceral adiposity was a strong and independent risk factor for coronary atherosclerosis even in lean individuals, which could be partially explained by its coalignment with pathological pro-inflammatory signaling.

Purpose: Pericardial adipose tissue had been shown to exert local effects on adjacent cardiac structures. Data regarding the mechanistic link between such measures and left atrial (LA) structural/functional remodeling, a clinical hallmark of early stage heart failure (HF) and atrial fibrillation (AF) incidence, in asymptomatic population remain largely unexplored. Methods: This retrospective analysis includes 356 subjects free from significant valvular disorders, atrial fibrillation, or clinical HF. Regional adipose tissue including pericardial and periaortic fat volumes, interatrial septal (IAS), and left atrioventricular groove (AVG) fat thickness were all measured by multidetector computed tomography (MDCT) (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). We measured LA volumes, booster performance, reservoir capacity as well as conduit function, and analyzed their association with adiposity measures. Results: All four adiposity measures were positively associated with greater LA volumes (all P < 0.05), while IAS and AVG fat were also related to larger LA kinetic energy and worse reservoir capacity (both P < 0.01). In multivariate models, IAS fat thickness remained independently associated with larger LA volumes, increased LA kinetic energy and ejection force (β-coef: 0.17 & 0.15, both P < 0.05), and impaired LA reservoir and conduit function (β-coef: −0.20 & −0.12, both P < 0.05) after adjusting for clinical variables. Conclusion: Accumulated visceral adiposity, especially interatrial fat depots, was associated with certain LA structural/functional remodeling characterized by impaired LA reservoir and conduit function though augmented kinetic energy and ejection performance. Our data suggested that interatrial fat burden may be associated with certain detrimental LA functions with compensatory LA adaptation in an asymptomatic population.

Background: The aortic root diameter (AoD) has been shown to be a marker of cardiovascular risk and heart failure (HF). Data regarding the normal reference ranges in Asians and their correlates with diastolic dysfunction using contemporary guidelines remain largely unexplored. Methods: Among 5343 consecutive population-based asymptomatic Asians with echocardiography evaluations for aortic root diameter (without/with indexing, presented as AoD/AoDi) were related to cardiac structure/function and N-terminal pro-brain B-type natriuretic peptide (Nt-ProBNP), with 245 participants compared with multidetector computed tomography (MDCT)-based aortic root geometry. Results: Advanced age, hypertension, higher diastolic blood pressure, and lower body fat all contributed to greater AoD/AoDi. The highest correlation between echo-based aortic diameter and the MDCT-derived measures was found at the level of the aortic sinuses of Valsalva (r = 0.80, p < 0.001). Age- and sex-stratified normative ranges of AoD/AoDi were provided in 3646 healthy participants. Multivariate linear regressions showed that AoDi was associated with a higher NT-proBNP, more unfavorable left ventricular (LV) remodeling, worsened LV systolic annular velocity (TDI-s′), a higher probability of presenting with LV hypertrophy, and abnormal LV diastolic indices except tricuspid regurgitation velocity by contemporary diastolic dysfunction (DD) criteria (all p < 0.05). AoDi superimposed on key clinical variables significantly expanded C-statistic from 0.71 to 0.84 (p for ∆AUROC: < 0.001). These associations were broadly weaker for AoD. Conclusion: In our large asymptomatic Asian population, echocardiography-defined aortic root dilation was associated with aging and hypertension and were correlated modestly with computed tomography measures. A larger indexed aortic diameter appeared to be a useful indicator in identifying baseline abnormal diastolic dysfunction.

Among 2085 asymptomatic subjects (age: 51.0 ± 10.7 years, 41.3% female) with data available on common carotid artery diameter (CCAD) and circulating total white blood cell (WBC) counts, higher circulating leukocytes positively correlated with higher high sensitivity C-reactive protein (hs-CRP). Higher WBC/segmented cells and monocyte counts were independently associated with greater relative wall thicknesses and larger CCADs, which in general were more pronounced in men and obese subjects (body mass index ≥ 25 kg/m2) (all P interaction: < 0.05). Using multivariate adjusting models, only the monocyte count independently predicted the left ventricular mass index (LVMi) (ß-Coef: 0.06, p = 0.01). Higher circulating WBC, segmented, and monocyte counts and a greater CCAD were all independently associated with a higher risk of heart failure (HF)/all-cause death during a median of 12.1 years of follow-up in fully adjusted models, with individuals manifesting both higher CCADs and monocyte counts incurring the highest risk of HF/death (adjusted hazard ratio: 2.81, 95% CI: 1.57. −5.03, p < 0.001; P interaction, 0.035; lower CCAD/lower monocyte as reference). We conclude that a higher monocyte count is associated with cardiac remodeling and carotid artery dilation. Both an elevated monocyte count and a larger CCAD may indicate a specific phenotype that confers the highest risk of HF, which likely signifies the role of circulating monocytes in the pathophysiology of heart failure with preserved ejection fraction (HFpEF).

Primary tumors of the heart and major vessels are rare. Angiosarcoma is the most frequent malignant tumor of the heart and usually involves the right atrium. Angiosarcoma originating from the pericardium is extremely rare and only several cases have been reported to date. The current study presents a case of primary angiosarcoma of pericardium with cardiac tamponade. After surgical treatment to relieve symptoms, the patient refused further therapies and died 3 months after diagnosis.

Central arterial stiffness has been shown to play a key role in cardiovascular disease. However, evidence regarding such arterial stiffness from various arterial segments in relation to B-type natriuretic peptide (BNP) remains elusive.A total of 1255 participants (47.8% men; mean age: 62.6 ± 12.3 [SD] years) with preserved left ventricular function (ejection fraction ≥50%) and ≥1 risk factors were consecutively studied. Arterial pulse wave velocity (PWV) by automatic device (VP-2000; Omron Healthcare) for heart-femoral (hf-PWV), brachial-ankle (ba-PWV), and heart-carotid (hc-PWV) segments were obtained and related to BNP concentrations (Abbott Diagnostics, Abbott Park, IL, USA).Subjects in the highest hf-PWV quartile were older and had worse renal function and higher blood pressure (all P < 0.05). Elevated PWV (m/s) was correlated with elevated BNP (pg/ml) (beta coefficient = 19.3, 12.4, 5.9 for hf-PWV, ba-PWV, hc-PWV respectively, all p < 0.05). After accounting for clinical co-variates and left ventricle mass index (LVMI), both hf-PWV and ba-PWV were correlated with higher BNP (beta coefficient = 8.3, 6.4 respectively, P < 0.01 for each). Adding both hf-PWV and ba-PWV to LVMI significantly expanded ROC in predicting abnormal BNP>100 pg/ml (both P < 0.01), but only hf-PWV presented significant integrated discrimination improvement to predict risk for BNP concentrations (0.7%, P = 0.029).A significant segmental PWV associated with biomarker BNP concentrations suggests that arterial stiffness is associated with myocardial damage.

Background: Metabolic syndrome (MS) associated with systemic inflammation identifies high-risk cardiovascular diseases (CVDs). Deteriorated renal function leads to poor cardiovascular outcomes. However, the relationship between such metabolic anomaly, systemic inflammation and renal function in patients diagnosed with peripheral arterial disease (PAD) remains largely unknown. Materials and methods: A total of 249 consecutive individuals meeting the study criteria from our outpatient clinics were enrolled in the study. Baseline demographic data and information regarding metabolic abnormalities [presented as Adult Treatment Panel (ATP) III scores], high-sensitivity C-reactive protein (Hs-CRP) level, and estimated renal function [calculated by the Modification of Diet in Renal Disease (MDRD) method] were obtained. High-risk PAD was defined by utilizing the ankle–brachial index (ABI) method. Results: Of all 249 subjects, 60 had diagnostic high-risk PAD. The prevalence of PAD increased in a significant trend with worsening ATP III scores. By utilizing a multivariate adjustment model, body mass index and worse renal function were independently associated with PAD (both p

Gold has been used in medicine for thousands of years. Nowadays, gold compounds contribute to the treatment of rheumatoid arthritis; gold alloys are used in implants in various fields of medicine; and colloid gold is used in immunogold electron microscopy. Advances in nanotechnology have resulted in novel gold nanoparticles, which possess distinct physical properties such as fluorescence. We have developed fluorescent gold nanoclusters (FANCs) that contain gold nanoparticles with a core dimension < 2 nm. Initial studies have shown that FANCs are a highly biocompatible marker with a fluorescence half-life of 9 days, and are suitable for in vitro and in vivo tracking of endothelial and endothelial progenitor cells. FANCs may also have novel chemical properties involved in regulation of endothelial cell function. This minireview discusses the future directions of biomedical research for FANCs.

We compared the cardiovascular diseases (CVD) and risk factors in patients with stage 3–5 chronic kidney disease (CKD) and those with diabetes mellitus by analyzing the MAGNET study data of residents in northern Taiwan. The reimbursement of lipid-lowering therapy was also examined. Of the 1607 participants, 63 (31 men) were found to have eGFR

Gene therapy, which is still at an experimental stage, is a technique that attempts to correct or prevent a disease by delivering genes into an individual's cells and tissues. In gene delivery, a vector is a vehicle for transferring genetic material into cells and tissues. Synthetic vectors are considered to be prerequisites for gene delivery, because viral vectors have fundamental problems in relation to safety issues as well as large-scale production. Among the physical approaches, ultrasound with its associated bioeffects such as acoustic cavitation, especially inertial cavitation, can increase the permeability of cell membranes to macromolecules such as plasmid DNA. Microbubbles or ultrasound contrast agents lower the threshold for cavitation by ultrasound energy. Furthermore, ultrasound-enhanced gene delivery using polymers or other nonviral vectors may hold much promise for the future but is currently at the preclinical stage. We all know aging is cruel and inevitable. Currently, among the promising areas for gene therapy in acquired diseases, the incidences of cancer and ischemic cardiovascular diseases are strongly correlated with the aging process. As a result, gene therapy technology may play important roles in these diseases in the future. This brief review focuses on understanding the barriers to gene transfer as well as describing the useful nonviral vectors or tools that are applied to gene delivery and introducing feasible models in terms of ultrasound-based gene delivery.