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Background: Obesity, 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 Findings: We 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, <45 g/L [malnourished]; high, ≥45 g/L [well-nourished]), and secondarily by the prognostic nutritional index (PNI) and Global Leadership Initiative on Malnutrition (GLIM) criteria. Cox proportional hazard models were used to examine a 1-year composite outcome of hospitalization for HF or all-cause mortality while adjusting for age, sex, and other clinical confounders. Our community-based cohort consisted of 2,096 (39.0%) lean-well-nourished (low BMI, high SA), 1,369 (25.8%) obese-well-nourished (high BMI, high SA), 1,154 (21.8%) lean-malnourished (low BMI, low SA), and 681 (12.8%) obese-malnourished (high BMI, low SA) individuals. Obese-malnourished participants were on average older (54.5 ± 11.4 years) and more often women (41%), with a higher mean waist circumference (91.7 ± 8.8 cm), the highest percentage of body fat (32%), and the highest prevalence of hypertension (32%), diabetes (12%), and history of cardiovascular disease (11%), compared to all other subgroups (all p < 0.001). N-terminal pro B-type natriuretic peptide (NT-proBNP) levels were substantially increased in the malnourished (versus well-nourished) groups, to a similar extent in lean (70.7 ± 177.3 versus 36.8 ± 40.4 pg/mL) and obese (73.1 ± 216.8 versus 33.2 ± 40.8 pg/mL) (p < 0.001 in both) participants. The obese-malnourished (high BMI, low SA) group also had greater left ventricular remodeling (left ventricular mass index, 44.2 ± 1.52 versus 33.8 ± 8.28 gm/m2; relative wall thickness 0.39 ± 0.05 versus 0.38 ± 0.06) and worse diastolic function (TDI-e' 7.97 ± 2.16 versus 9.87 ± 2.47 cm/s; E/e' 9.19 ± 3.01 versus 7.36 ± 2.31; left atrial volume index 19.5 ± 7.66 versus 14.9 ± 5.49 mL/m2) compared to the lean-well-nourished (low BMI, high SA) group, as well as all other subgroups (p < 0.001 for all). Over a median 3.6 years (interquartile range 2.5 to 4.8 years) of follow-up, the obese-malnourished group had the highest multivariable-adjusted risk of the composite outcome (hazard ratio [HR] 2.49, 95% CI 1.43 to 4.34, p = 0.001), followed by the lean-malnourished (HR 1.78, 95% CI 1.04 to 3.04, p = 0.034) and obese-well-nourished (HR 1.41, 95% CI 0.77 to 2.58, p = 0.27) groups (with lean-well-nourished group as reference). Results were similar when indexed by other anthropometric indices (waist circumference and body fat) and other measures of nutritional status (PNI and GLIM criteria). Potential selection bias and residual confounding were the main limitations of the study., Conclusions: In 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., Competing Interests: CSPL: I have read the journal’s policy and the authors of this manuscript have the followingcompeting interests:Grants from National Medical Research Council Singapore, non-financial support from Boston Scientific, non-financial support and other from Bayer, non-financial support from Thermofisher, non-financial support from Vifor Pharma, other from Takeda, other from Merck, other from Astra Zeneca, other from Janssen Research & Development, other from LLC, other from Menarini, other from Boehringer Ingelheim, other from Abbott Diagnostics, other from DC Devices, other from PCT/SG2016/050217 Patent pending, outside the submitted work. All other authors have declared that no competing interests exist.

Cardiac remodeling is common in the athletes. Little data is available regarding the cardiac remodeling on the recently proposed 4 sport disciplines among the elite university athletes.A total of 7639 athletes participated in the 2017 Taipei Summer Universiade. Cardiac evaluation via history, ECG, and echocardiography were performed in 826 athletes who signed up for Check Up Your Heart. Athletes were grouped into one of 4 sport disciplines Skill, Power, Mixed, and Endurance.After excluding 66 participants with missing demographic data, 13 missing echocardiographic data, and 24 inadequate echocardiographic images, a total number of 723 university athletes (mean age 23 ± 3 years, 419 males) from 99 countries engaging in 25 different sporting events were analyzed. Electrocardiograms showed that Endurance group had a slower heart rate and higher percentage of left ventricular (LV) hypertrophy (39%). Echocardiograms showed there were significant differences in LV mass index (P < .001), LV geometry (P < .001), left atrial (LA) dilatation (P = .026), right ventricular (RV) dilatation (P < .001), right atrial (RA) dilatation (P < .0001), and tricuspid annular plane systolic excurse (P = .006). LV ejection fraction, LV strain, RV strain, and LV diastolic function showed no difference in 4 sport disciplines.Eccentric LV hypertrophy was the most common type of cardiac remodeling in the university athletes participated in 2017 Taipei Summer Universiade. Adaptive changes in chamber size were more commonly seen in Endurance sport. RA dilatation was the most sensitive to hemodynamic demand, followed by RV dilatation, LA dilatation, and LV dilatation.

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) (<4, 4-6, 6-8, 8-10, > = 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<0.05). Both HU and Gout groups were associated with lower LV e' (coefficient: -0.086, -0.05), higher E/e' (coefficient: 0.075, 0.35, all p <0.05), larger LA volume, and higher DD risk (adjusted ORs: 1.21 and 1.91 using Non-HU as reference, respectively, both p <0.05). SUA set at 7.0 mg/dL provided the optimal cut-off for identifying DD, with markedly lower e' (HU: 8.94 vs 8.07, Gout: 7.94 vs 7.26 cm/sec) and higher LV E/e' in HU/Gout women than in men (HU: 7.84 vs 9.79 cm/sec for men and women, respectively, all p <0.05). Hyperuricemia, even at a relatively low clinical cut-off, was associated with unfavorable remodeling and was tightly linked to diastolic dysfunction. The presence of gout likely aggravated these conditions. Women with hyperuricemia or gout had worse diastolic indices than men despite similar degrees of LV remodeling., Competing Interests: The authors have declared that no competing interests exist.

Background: The triglyceride-glucose (TyG) index has been reported to be a simple and reliable surrogate marker of insulin resistance. The aim of this study was to investigate associations between the TyG index and echocardiographic parameters including left ventricular mass (LVM), left atrial diameter (LAD) and left ventricular ejection fraction (LVEF), and markers of peripheral artery disease, ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV). Methods: A total of 823 (483 males and 340 females) patients were enrolled from 2007 to 2011 at a regional hospital in southern Taiwan. Multivariable stepwise linear regression analysis was performed to identify the factors related to echocardiographic parameters and peripheral artery disease. Results: The patients were stratified into four groups according to TyG index quartile. Multivariable stepwise linear regression analysis showed that a higher TyG index was associated with elevated observed/predicted LVM ( p = 0.081), increased LAD ( p = 0.004), decreased LVEF ( p = 0.003) and lower ABI ( p = 0.030), but not observed/predicted LVM and baPWV. Conclusions: A high TyG index was significantly associated with high LAD, low LVEF and low ABI. However, the TyG index was not significantly associated with inappropriate LVM or baPWV. The results suggest that the TyG index, as a simple indicator of insulin resistance, may reflect cardiac remodeling and dysfunction and atherosclerosis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Angiotensin receptor neprilysin inhibitor (ARNI) was recommended by major guidelines as the frontline therapy for heart failure with reduced ejection fraction (HFrEF) since its clinical benefit was proved in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial. However, little is known about its safety and effectiveness in real-world practice, often with sicker and more fragile patients. In addition, East Asia population is underrepresented in PARADIGM-HF trial.Methods: We performed a retrospective analysis of patients who received ARNI in 3 medical institutes located in Northern Taiwan. Patients who received a prescription of at least 30 days of ARNI were enrolled. The date of first prescription was defined as the index date, and a period of 12 months preceding the index date was defined as the baseline period.Results: A total of 452 patients were identified (age: 61.9 ± 15.0, male: 79.4%). Compared to PARADIGM-HF populations, our patients had higher values of baseline serum creatinine (mean: 1.5 vs 1.1 mg/dL) and B-type natriuretic peptide (BNP; median: 554.5 vs 255 pg/mL). After 12 months, 41.6% of the patients received less than half of the standard dose. Overall, all-cause death, cardiovascular death, and heart failure readmission rate were 3.0%, 1.1%, and 6.9% in 12 months, respectively. In those who had both baseline and 12-month data, renal function did not change (1.7-1.8 mg/dL, P = .091), left ventricular ejection fraction improved (30.8%-36.8%, P < .001), BNP decreased (777.0-655.8 pg/mL, P = .032), and uric acid decreased (7.5-7.1 mg/dL, P = .009).Conclusion: In our study, patients with HFrEF had higher BNP and serum creatinine level at baseline and had received lower dose of ARNI than the PARADIGM-HF populations. Angiotensin receptor neprilysin inhibitor appeared to be safe as regard renal function and effective in real-world practice. Left ventricular reverse remodeling was observed 1 year after heart failure medication treatment, including ARNI. [ABSTRACT FROM AUTHOR]

Background: Cyclophilin A (CyPA) concentration increases in acute coronary syndrome. In an animal model of acute myocardial infarction, administration of angiotensin-converting-enzyme inhibitor was associated with lower left ventricular (LV) CyPA concentration and improved LV performance. This study investigated the relationships between changes in plasma CyPA concentrations and LV remodeling in patients with ST-elevation myocardial infarction (STEMI)., Methods and Results: We enrolled 55 patients who underwent percutaneous coronary intervention for acute STEMI. Plasma CyPA, matrix metalloproteinase (MMP), interleukin-6 and high-sensitivity C-reactive protein concentrations were measured at baseline and at one-month follow-up. Echocardiography was performed at baseline and at one-, three-, and six-month follow-up. Patients with a decrease in baseline CyPA concentration at one-month follow-up (n = 28) had a significant increase in LV ejection fraction (LVEF) (from 60.2 ± 11.5% to 64.6 ± 9.9%, p < 0. 001) and preserved LV synchrony at six months. Patients without a decrease in CyPA concentration at one month (n = 27) did not show improvement in LVEF and had a significantly increased systolic dyssynchrony index (SDI) (from 1.170 ± 0.510% to 1.637 ± 1.299%, p = 0.042) at six months. Multiple linear regression analysis showed a significant association between one-month CyPA concentration and six-month LVEF. The one-month MMP-2 concentration was positively correlated with one-month CyPA concentration and LV SDI. Conclusions : Decreased CyPA concentration at one-month follow-up after STEMI was associated with better LVEF and SDI at six months. Changes in CyPA, therefore, may be a prognosticator of patient outcome.

Background: Cross-sectional studies investigated the impact of renin-angiotensin system (RAS) gene polymorphism on left ventricular mass index (LVMI) with conflicting results. We conducted a longitudinal study to investigate the influence of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) and angiotensinogen (AGT) M235T and angiotensin II type 1 receptor (AT1R) A1166C gene polymorphisms on the LVMI and geometry., Methods: Of 1500 people screened, 110 nondiabetic normotensive elderly Chinese persons were recruited and received echocardiography at baseline and at the 2nd and 4th year follow-up. No participants had a history of organic heart disease or chronic medication. The gene polymorphisms were analyzed by using polymerase chain reaction., Results: Participant age was 71.9 +/- 3.9 years (range 60-81 years). The prevalence of concentric remodeling, eccentric hypertrophy, and concentric hypertrophy was significantly increased as well as LVMI after 4 years (all p <.05). These changes and the magnitude of LVMI increase were significantly higher in participants carrying the ACE D allele than non-D-allele carriers (all p <.05). This association was still significant in multivariate analyses (p

Introduction: Traditional Chinese Medicine (TCM) has a broad application in healthcare, with Danshen being a notable herb used in Eastern medicine for cancer treatment. This study aims to explore the relationship between Danshen use and cardiovascular risks among bladder cancer patients. Methods: Patients were selected based on a confirmed diagnosis of bladder cancer with specific inclusion and exclusion criteria to control for certain comorbidities and treatments. Utilizing Taiwan’s National Health Insurance data from 2003 to 2013, this retrospective, population-based study identified three groups: 525 patients treated with Danshen, 6,419 patients not treated with TCM, and 4,356 patients treated with TCM but not with Danshen. The Cox proportional hazard model was employed to estimate the risks of Major Adverse Cardiovascular Events (MACE) and mortality while accounting for various confounders. Results: The overall incidence of MACEs was significantly lower in the Danshen group (5%) compared to the TCM (8.1%) and non-TCM (9.9%) groups (p < 0.001). The Cox model revealed that bladder cancer patients treated with Danshen had the lowest risk of MACE (adjusted hazard ratio, 0.56; 95% confidence interval, 0.38–0.84) and all-cause mortality (adjusted hazard ratio, 0.60; 95% confidence interval, 0.44–0.82). Discussion: The findings suggest that Danshen reduces the risk of MACE and allcause mortality in bladder cancer patients, highlighting its potential benefits. This underpins the necessity for further research to substantiate the cardiovascular benefits of Danshen in bladder cancer patients and potentially broaden its application in oncology healthcare. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates the potential impact of cholinesterase inhibitors (ChEIs) on patients with heart failure (HF) and dementia. ChEIs are known to boost acetylcholine levels and benefit cognition in patients with dementia; however, their effect on patients with HF is uncertain. This study aimed to assess whether cardiovascular events and mortality among patients with HF and dementia are altered by ChEI therapy. Methods: Data from the National Health Insurance Research Database in Taiwan were retrospectively analyzed. Dementia patients diagnosed with HF were followed for 5 years until all-cause mortality, cardiovascular mortality, hospitalization for worsening HF, or the end of the study. Multivariable Cox models and inverse probability of treatment weighting (IPTW) were employed. Results: Out of 20,848 patients with dementia, 5138 had HF. Among them, 726 were ChEI users and 4412 were non-users. Based on IPTW, the ChEI users had significantly lower estimated risks of all-cause mortality [hazard ratio (HR) 0.43; 95% confidence interval (CI) 0.38–0.49, p < 0.001] and cardiovascular mortality (HR 0.41; 95% CI 0.33–0.53, p < 0.001) compared with the non-users, but there was no significant difference in hospitalization for worsening HF (HR 0.73; 95% CI 0.51–1.05, p = 0.091) after 5 years. The survival benefits of ChEIs were consistent across subgroups. Conclusions: The results of this retrospective cohort study suggest that ChEIs may be beneficial in reducing all-cause and cardiovascular mortality in patients with dementia with HF. Further research is needed to validate these findings and explore the potential benefits of ChEIs in all patients with HF, including those without dementia. [ABSTRACT FROM AUTHOR]

Left Ventricular Remodeling in Pacing Dogs. Introduction: Right ventricle (RV) apical pacing is associated with increased incidence of heart failure due to left ventricle (LV) desynchronization. We aim to investigate extracellular matrix (ECM) remodeling of the LV in dogs with atria-sensed RV apical pacing. Methods and Results: Dogs with pacemakers underwent AV nodal ablation. After 12 weeks of atria-sensed obligatory RV pacing, LVs were separated into septum and lateral wall for analysis. Zymographic activity, including matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinase-1 (TIMP-1), TIMP-3, collagen transcript expression, and histology were examined in opposite portions of the LV to identify possible ECM remodeling changes by RV apical pacing. Compared with sham-operated dogs, increased interstitial fibrosis and fragmentation of myofibrils was found in the LV lateral wall in the pacing group. Collagen type II mRNA showed a significant 2-fold increase in the LV lateral wall in the pacing group. Although collagen type I mRNA was increased, the difference was not significant. Zymography demonstrated MMP-9 activity was enhanced in both the LV lateral wall and septum in the pacing group, but MMP-2 activity was enhanced in the LV lateral wall. Immunfluorescence stain confirmed the activation of MMP-2 and MMP-9 in the LV lateral wall in the pacing group. Protein expression of TIMP-1 and TIMP-3 showed regional differences in the pacing group and both proteins were increased in the LV lateral wall. Conclusion: LV dyssynchrony by RV apical pacing elicits heterogeneous ECM remodeling in the LV. These findings assist in the elucidation of the pathophysiology of LV desynchronization. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1142-1149) [ABSTRACT FROM AUTHOR]

Background: Temporary ventricular‑assisted device (VAD) provides timely organ perfusion in patients with cardiogenic shock and serves as a bridge to heart transplant. Intravenous levosimendan could provide pharmacologic inotropic support. Aim: We aimed to investigate the adjuvant efficacy of levosimendan in patients with temporary VAD, especially for VAD weaning. Methods: We retrospectively reviewed the medical records of patients receiving temporary VAD for cardiogenic shock between January 2017 and May 2019 in a medical center in Taiwan. Patients were divided into the levosimendan (n = 9, administered levosimendan immediately after VAD), and control groups (n = 20, no levosimendan administered). The biochemistry of systemic perfusion was compared at 1 and 3 days after VAD. After 2 months, the cardiac function of the patients with successful VAD weaning was evaluated by echocardiography. At 6 months follow‑up, survival outcome and Kaplan–Meier survival curves were presented. Results: In total, 29 patients receiving temporary VAD for cardiogenic shock were enrolled, including 9 patients treated with levosimendan infusion. In the levosimendan group, both mean arterial pressure and lactate level decreased significantly (P = 0.037 and 0.023, respectively), and the ratio of arterial oxygen partial pressure to fractional inspired oxygen improved significantly (P = 0.048). No difference in inotropes tapering, consciousness, systemic perfusion biochemistry, and cardiac enzymes. Echocardiography showed significantly improved systolic function and pulmonary artery pressure 2 months later (P = 0.043 and 0.046, respectively) in patients with successful weaning. The levosimendan group had a better weaning rate (P = 0.013) and lower mortality rate (P = 0.571) at 6‑month follow‑up. Conclusion: The levosimendan group showed a better weaning rate and lower mortality rate. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic has impacted human lifestyles around the world, causing huge distress in terms of public health systems, emergency response capacity and economic development. The causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with respiratory involvement, cardiovascular-related diseases, and ultimately causes multiple organ failure and death in severely affected individuals. Thus, effective prevention or early treatment of COVID-19 is critical. An effective vaccine offers a way out of the pandemic for governments, the scientific community and people worldwide, but we still lack effective drug therapies, including treatments for the prevention and treatment of COVID-19. This had led to a high global demand for many complementary and alternative medicines (CAMs). Moreover, many healthcare providers are now requesting information about CAMs that prevent, relieve, or treat the symptoms of COVID-19 and even alleviate vaccine-related side effects. Experts and scholars must therefore become familiar with the use of CAMs in COVID-19, current research directions and effectiveness of CAMs for COVID-19. This narrative review updates the current status and research worldwide on the use of CAMs for COVID-19. The review provides reliable evidence on theoretical viewpoints and therapeutic efficacies of CAM combinations, and evidence in support of the therapeutic strategy of Taiwan Chingguan Erhau (NRICM102) against moderate-to-severe novel coronavirus infectious disease in Taiwan. [ABSTRACT FROM AUTHOR]

Background: The glycemic continuum often indicates a gradual decline in insulin sensitivity leading to an increase in glucose levels. Although prediabetes is an established risk factor for both macrovascular and microvascular diseases, whether prediabetes is independently associated with the risk of developing atrial fibrillation (AF), particularly the occurrence time, has not been well studied using a high-quality research design in combination with statistical machine-learning algorithms. Methods: Using data available from electronic medical records collected from the National Taiwan University Hospital, a tertiary medical center in Taiwan, we conducted a retrospective cohort study consisting 174,835 adult patients between 2014 and 2019 to investigate the relationship between prediabetes and AF. To render patients with prediabetes as comparable to those with normal glucose test, a propensity-score matching design was used to select the matched pairs of two groups with a 1:1 ratio. The Kaplan–Meier method was used to compare the cumulative risk of AF between prediabetes and normal glucose test using log-rank test. The multivariable Cox regression model was employed to estimate adjusted hazard ratio (HR) for prediabetes versus normal glucose test by stratifying three levels of glycosylated hemoglobin (HbA1c). The machine-learning algorithm using the random survival forest (RSF) method was further used to identify the importance of clinical factors associated with AF in patients with prediabetes. Results: A sample of 14,309 pairs of patients with prediabetes and normal glucose test result were selected. The incidence of AF was 11.6 cases per 1000 person-years during a median follow-up period of 47.1 months. The Kaplan–Meier analysis revealed that the risk of AF was significantly higher in patients with prediabetes (log-rank p < 0.001). The multivariable Cox regression model indicated that prediabetes was independently associated with a significant increased risk of AF (HR 1.24, 95% confidence interval 1.11–1.39, p < 0.001), particularly for patients with HbA1c above 5.5%. The RSF method identified elevated N-terminal natriuretic peptide and altered left heart structure as the two most important risk factors for AF among patients with prediabetes. Conclusions: Our study found that prediabetes is independently associated with a higher risk of AF. Furthermore, alterations in left heart structure make a significant contribution to this elevated risk, and these structural changes may begin during the prediabetes stage. [ABSTRACT FROM AUTHOR]

Background and purposes: The long-term risk of stroke in women with preeclampsia/eclampsia is a concerning issue. In this study we further investigated different stroke subtypes and differentiated follow-up time intervals. Methods: Between 2000 and 2017, 1,384,427 pregnant women were registered in the National Health Insurance Research Database in Taiwan. After excluding women with previous stroke history and exact matching with all confounders, 6,053 women with preeclampsia/eclampsia and 24,212 controls were included in the analysis sample. Results: Over the 17-year follow-up, the adjusted hazard ratio (aHR) for stroke in women with preeclampsia/eclampsia was 2.05 (95% confidence interval, CI = 1.67–2.52, p<0.001). The 17 years overall aHR of both ischemic and hemorrhagic stroke were 1.98 and 3.45, respectively (p<0.001). The stroke subtypes, hemorrhagic and ischemic, had different time trend risks, and hemorrhagic stroke risks kept higher than that of ischemic stroke. The aHR of ischemic stroke reached a peak during 1–3 years after childbirth (aHR = 3.09). The aHR of hemorrhagic stroke reached a peak during 3–5 years (aHR = 7.49). Conclusions: Stroke risk persisted even after decades, for both ischemic and hemorrhagic subtypes. Women with preeclampsia/eclampsia history should be aware of the long-term risk of stroke. [ABSTRACT FROM AUTHOR]

The incidence rate of AL (light-chain) amyloidosis is not known in Asia. We conducted a retrospective cohort study using the Taiwan National Healthcare Insurance Research database and Death Registry to estimate incidence and all-cause case fatality rates, and characteristics of patients with AL amyloidosis in Taiwan. All patients with confirmed, newly diagnosed AL amyloidosis from 01-Jan-2016 until 31-Dec-2019 were enrolled and followed up until dis-enrolment, death or study end (31-Dec-2019). There were 841 patients with newly diagnosed AL amyloidosis with median age of 61.4 years and 58.7% were men. At diagnosis, cardiac, renal and liver-related diseases were present in 28.54%, 23.19% and 2.14% of patients, respectively. AL amyloidosis age-adjusted annual incidence was 5.73 per million population in 2016 and 5.26 per million population in 2019. All-cause case fatality ranged from 1.7 to 2.9% over the study period and was highest (~10%) in patients ≥ 80 years. Survival was significantly lower in patients with co-morbid cardiac, renal, or liver-related diseases which could indicate organ involvement. The incidence of AL amyloidosis in Taiwan appears to be similar to Western countries. The poor prognosis in patients with co-morbid diseases highlights the need for earlier diagnosis. [ABSTRACT FROM AUTHOR]

Summary: Despite a variety of available medical therapies and electrophysiological interventions, many heart failure patients still have a poor quality of life and a poor prognosis. Cardiac transplantation is currently the main treatment for end-stage heart failure in Taiwan but it is sometimes accompanied by rejection, immune compromise, and the adverse side effects of antirejection drugs. In addition, there is a shortage of donor grafts worldwide. For these reasons, other surgical interventions that alleviate ischemia and valvular dysfunction, and also reverse ventricular remodeling, should be considered before transplantation is advised. In this review, we discuss current nontransplant surgical management strategies for end-stage heart failure in terms of coronary revascularization, mitral reconstruction, ventricular reconstruction, and stem-cell regeneration of the myocardium. [Copyright &y& Elsevier]

Backgrounds: Chronic kidney disease (CKD) is underdiagnosed in children with congenital heart disease (CHD). Our aim was to study the incidence of CKD in CHD children and identify risk factors for CKD. Methods: CHD patients were enrolled from the Kaohsiung Veterans General Hospital database between 2010 and 2019. Patient age at enrollment was age at first visit to the hospital. The end of follow-up was marked by the last measurement of serum creatinine, urine protein-to-creatinine ratio (UPCR), or urine microalbumin-to-creatinine ratio (UACR) after enrollment, and only patients who underwent the aforementioned tests in 2 different years were included. Patients with an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 were diagnosed as having CKD and were further classified into clinically recognized CKD (CR-CKD, defined as eGFR <60 mL/min/1.73m2, UPCR >0.5, or UACR >30 mg/g) and non-clinically recognized CKD (NCR-CKD). Their demographic data, CHD category, heart surgery types, medications, and contrast-related examinations during follow-up were collected. Results: The study included 359 CHD patients, of whom 167 (46.5%) developed CKD (18 patients with CR-CKD and 341 with NCR-CKD). Patients with CR-CKD were significantly older at enrollment than patients with NCR-CKD. Corrective heart surgery may be a protective factor for CKD. Furthermore, cyanotic heart disease, two or more image-related contrast exposures, and diuretic use may be associated with CKD. Conclusion: CHD patients have a high incidence of CKD. The early detection of CKD and prompt corrective heart surgery for CHD may be beneficial for kidney function. [ABSTRACT FROM AUTHOR]

Background: To assess the associations of various HbA1c measures, including a single baseline HbA1c value, overall mean, yearly updated means, standard deviation (HbA1c-SD), coefficient of variation (HbA1c-CV), and HbA1c variability score (HVS), with microvascular disease (MVD) risk in patients with type 2 diabetes. Methods: Linked data between National Cheng Kung University Hospital and Taiwan's National Health Insurance Research Database were utilized to identify the study cohort. The primary outcome was the composite MVD events (retinopathy, nephropathy, or neuropathy) occurring during the study follow-up. Cox model analyses were performed to assess the associations between HbA1c measures and MVD risk, with adjustment for patients' baseline HbA1c, demographics, comorbidities/complications, and treatments. Results: In the models without adjustment for baseline HbA1c, all HbA1c variability and mean measures were significantly associated with MVD risk, except HVS. With adjustment for baseline HbA1c, HbA1c-CV had the strongest association with MVD risk. For every unit of increase in HbA1c-CV, the MVD risk significantly increased by 3.42- and 2.81-fold based on the models without and with adjustment for baseline HbA1c, respectively. The associations of HbA1c variability and mean measures with MVD risk in patients with baseline HbA1c < 7.5% (58 mmol/mol) were stronger compared with those in patients with baseline HbA1c ≥ 7.5% (58 mmol/mol). Conclusions: HbA1c variability, especially HbA1c-CV, can supplement conventional baseline HbA1c measure for explaining MVD risk. HbA1c variability may play a greater role in MVD outcomes among patients with relatively optimal baseline glycemic control compared to those with relatively poor baseline glycemic control. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the association between T‐wave morphology and impaired left ventricular ejection fraction (LVEF) in patients with complete left bundle branch block (cLBBB), and the predictive value of T‐wave morphology for response to cardiac resynchronization therapy (CRT). Methods and Results: We enrolled 189 patients with cLBBB on electrocardiogram performed between January 2007 and December 2011 who underwent standard echocardiography. Repolarization parameters, including the QRS‐to‐T angle (TCRT), T‐wave morphology dispersion (TMD), T‐wave loop area (PL), and T‐wave residuum (TWR), were reconstructed from digital standard 12‐lead electrocardiograms by T‐wave morphology analysis. CRT response was defined as ≥15% reduction in left ventricular end‐systolic volume at 12 months after CRT implantation. The clinical outcome endpoint was a composite of heart failure hospitalization, heart transplantation, or death during follow up (mean, 5.8 years). On logistic regression, a higher heart rate, longer QRS duration, increased TMD, and larger TWR were all independently associated with LVEF < 40%. Among 40 patients who underwent CRT, those with a larger TMD (P =.007), larger PL (P =.025), and more negative TCRT (P =.015) had better response to CRT. A large TMD (P =.018) and large PL (P =.003) were also independent predictors of the clinical outcome endpoint. Conclusions: Increases in repolarization heterogeneity in patients with cLBBB are associated with impaired LVEF. A large TMD and large PL may be useful as additional predictors of response to CRT, improving patient selection for CRT. [ABSTRACT FROM AUTHOR]

Background: Patients with reduced ejection fraction have high rates of mortality and readmission after hospitalization for heart failure. In Taiwan, heart failure disease management programs (HFDMPs) have proven effective for reducing readmissions for decompensated heart failure or other cardiovascular causes by up to 30%. However, the benefits of HFDMP in different populations of heart failure patients is unknown.Method: This observational cohort study compared mortality and readmission in heart failure patients who participated in an HFDMP (HFDMP group) and heart failure patients who received standard care (non-HFDMP group) over a 1-year follow-up period after discharge (December 2014 retrospectively registered). The components of the intervention program included a patient education program delivered by the lead nurse of the HFDMP; a cardiac rehabilitation program provided by a physical therapist; consultation with a dietician, and consultation and assessment by a psychologist. The patients were followed up for at least 1 year after discharge or until death. Patient characteristics and clinical demographic data were compared between the two groups. Cox proportional hazards regression analysis was performed to calculate hazard ratios (HRs) for death or recurrent events of hospitalization in the HFDMP group in comparison with the non-HFDMP group while controlling for covariates.Results: The two groups did not significantly differ in demographic characteristics. The risk of readmission was lower in the HFDMP group, but the difference was not statistically significant (HR = 0.36, p = 0.09). In patients with ischemic cardiomyopathy, the risk of readmission was significantly lower in the HFDMP group compared to the non-HFDMP group (HR = 0.13, p = 0.026). The total mortality rate did not have significant difference between this two groups.Conclusion: The HFDMP may be beneficial for reducing recurrent events of heart failure hospitalization, especially in patients with ischemic cardiomyopathy.Trial Registration: Longitudinal case-control study ISRCTN98483065 , 24/09/2019, retrospectively registered. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether long-term exposure to airborne hydrocarbons, including volatile organic compounds, increases the risk of developing retinal vein occlusion (RVO) among the population of Taiwan. A retrospective cohort study involving 855,297 people was conducted. Cox proportional hazards regression analysis fitted the multiple pollutant models for two targeted pollutants, including total hydrocarbons (THC), nonmethane hydrocarbons (NMHC) were used, and the risk of RVO was estimated. The chi-squared test and one-way analysis of variance were used to test differences in demographics and comorbidity distribution among tertiles of the targeted pollutants. Before controlling for multiple pollutants, hazard ratios for the overall population were 19.88 (95% CI: 17.56–22.50) at 0.51-ppm increases in THC and 4.33 (95% CI: 3.97–4.73) at 0.27-ppm increases in NMHC. The highest adjusted hazard ratios for different multiple pollutant models of each targeted pollutant were statistically significant (all p values were ≤0.05) for all patients at 29.67 (95% CI: 25.57–34.42) for THC and 16.24 (95% CI: 14.14–18.65) for NMHC. Our findings suggest that long-term exposure to THC and NMHC contribute to RVO development. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) has a high incidence and prevalence worldwide, and chronic glomerulonephritis (CGN) is one of the main causes of CKD. Therefore, it is important to diagnose and treat CGN early. The purpose of this study is to analyze the prescription patterns and frequencies of Chinese herbal products (CHPs) for CGN by using a hospital-based database from the Chang Gung Memorial Hospital (CGMH), a large, tertiary hospital system in Taiwan, and to evaluate the safety and possible efficacy of CHPs by blood test. The International Classification of Disease Ninth Revision (ICD-9) code 582 was used to identify patients with CGN. From 2004 to 2015, a total of 54726 CHP prescriptions for CGN were provided. Association rule mining was used to analyze the prevalent of CHP combination patterns in treating CGN. Jia-Wei-Xiao-Yao-San (JWXYS) and Gorgon (Euryale feroxSalisb.) were the most frequently prescribed herbal formula (HF) and single herb (SH), respectively. The most frequently prescribed combination of CHPs was that of JWXYS with Bu-Yang-Huan-Wu-Tang (BYHWT) in CGMH. In statistical, the level of eGFR in Stage 3a and 3b group was increasing after treatment in 6 and 12 months and might not cause the renal function to worsen within 12-month treatments. To the best of our knowledge, this is the first pharmacoepidemiological study to review CHP treatments for CGN. However, additional studies and clinical trials are needed to provide data on the safety and efficacy of these CHPs. [ABSTRACT FROM AUTHOR]

Objective: The transition from childhood to teenaged years is associated with increased testosterone and a decreased iron status. It is not clear whether higher testosterone levels cause the decreased iron status, and to what extent, obesity-related inflammation influences the iron-testosterone relationship. The aim of the present study was to examine relationships of testosterone, iron status, and anti-/proinflammatory cytokines in relation to nutritional status in boys and young adolescent Taiwanese males. Methods: In total, 137 boys aged 7~13 yr were included. Parameters for obesity, the iron status, testosterone, and inflammatory markers were evaluated. Results: Overweight and obese (ow/obese) boys had higher mean serum testosterone, interleukin (IL)-1β, and nitric oxide (NO) levels compared to their normal-weight counterparts (all p<0.05). Mean serum ferritin was slightly higher in ow/obese boys compared to normal-weight boys, but this did not reach statistical significance. A multiple linear regression showed that serum ferritin (β = -0.7470, p = 0.003) was inversely correlated with testosterone, while serum IL-10 (β = 0.3475, p = 0.009) was positively associated with testosterone after adjusting for covariates. When normal-weight boys were separately assessed from ow/obesity boys, the association between testosterone and serum ferritin became stronger (β = -0.9628, p<0.0001), but the association between testosterone and IL-10 became non-significant (β = 0.1140, p = 0.4065) after adjusting for covariates. In ow/obese boys, only IL-10 was weakly associated with serum testosterone (β = 0.6444, p = 0.051) after adjusting for age. Conclusions: Testosterone and serum ferritin are intrinsically interrelated but this relationship is weaker in ow/obese boys after adjusting for age. [ABSTRACT FROM AUTHOR]

Few data exist on the clinical outcomes of selective aspiration thrombectomy during primary percutaneous coronary intervention (PPCI).This was a nationwide retrospective cohort study. Patients who were diagnosed with ST-elevation myocardial infarction (STEMI) and received primary percutaneous coronary intervention (PCI) from July 2009 to December 2011 were identified from the National Health Insurance Research Database of Taiwan. Propensity score weighting was used to balance the covariates between the 2 study groups. The primary endpoints were all-cause mortality and stroke during hospitalization and at 30 days and 1 year of follow-up. Subgroup analyses were performed based on the hospital and physician volume of primary PCI.A total of 9100 ST-elevation myocardial infarction patients (29.4% of patients receiving aspiration thrombectomy and conventional PPCI vs 70.6% receiving PPCI alone) were identified. The incidence rates of all-cause mortality were comparable between the 2 groups during hospitalization (21.0 vs 27.37/100 person-months; P = .29) and 1-year follow-up (0.81 vs 1.26/100 person-months; P = .85). There were no significant differences in the stroke rates between the 2 groups during hospitalization (1.1 vs 2.34/100 person-months; P = .3) and 1-year follow-up (0.09 vs 0.15/100 person-months; P = .85). For the patients who survived to discharge, the post-discharge 1-year mortality was lower in the aspiration thrombectomy group of patients in whom the procedures were performed by physicians with a high volume of PPCI (hazard ratio: 0.47; 95% confidence interval: 0.24-0.94; P = .03).In this nationwide cohort study, selective aspiration thrombectomy at the operation's discretion had a comparable mortality rate compared with PCI alone and did not increase the risk of stroke. In the patients treated by physicians with a high volume of PPCI, aspiration thrombectomy appeared to have a beneficial effect on post-discharge survival at 1 year.

Introduction Myocardial iron overload leading to congestive heart failure (HF) or arrhythmias is a recognized complication in thalassemia patients undergoing chronic blood transfusion. The relationship between myocardial iron load, subclinical systolic dysfunction, and clinical events remains less well known. Materials and Methods We studied a total of 77 subjects, comprising 37 thalassemia patients (mean age: 24.2 ± 5.5 years) with a history of repeated blood transfusions, in addition to 40 age- and gender-matched controls (mean age: 24 ± 4.5 years). Serum ferritin levels were checked in all subjects, as well as semiautomated quantification of left ventricular ( LV) longitudinal, circumferential, and radial deformations assessed by two-dimensional (2D) speckle tracking analysis. Results Compared with the control group, thalassemia patients showed significantly larger LV mass index and lower myocardial deformations (P < 0.05), but left ventricular ejection fraction ( LVEF) did not differ significantly (P = 0.233). There was a significant linear correlation between serum ferritin level and longitudinal (r = 0.44, P = 0.0078) and radial strain (r = −0.46, P = 0.0051), with optimal cutoff provided to be −15.48%, −21.31%, and 26.67% for longitudinal, circumferential, and radial strain in predicting clinical events, respectively. During a median of 802.5 days follow-up, 11 clinical composites (HF incidence, ventricular tachyarrhythmia, and death) occurred (N = 9 subjects); subjects with composites had significantly reduced longitudinal and radial strain compared to those without (both P < 0.05). After adjusting for age, sex, serum ferritin level, and LV mass index, a worsening of longitudinal strain remained as an independent predictor of clinical events and death ( HR: 6.05, P = 0.033). Conclusion Subclinical systolic dysfunction appears more likely in thalassemia subjects with a history of repeated blood transfusions, which further correlated with serum ferritin levels. In addition, worsening LV myocardial deformation parameters may play an independent role in predicting clinical outcomes beyond traditional measures in this population. [ABSTRACT FROM AUTHOR]

Aims Connective tissue growth factor ( CTGF) is an emerging marker for tissue fibrosis. We investigated the association between CTGF and cardiac diastolic function using cellular and animal models and clinical human data. Methods and results A total of 125 patients with a diagnosis of diastolic heart failure ( DHF) were recruited from 1283 patients of the Taiwan Diastolic Heart Failure Registry. The severity of DHF was determined by tissue Doppler imaging (E/e′). Cardiac magnetic resonance imaging ( CMRI) was used to evaluate myocardial fibrosis in some of the patients ( n = 25). Stretch of cardiomyocytes on a flexible membrane base serves as a cellular phenotype of cardiac diastolic dysfunction ( DD). A canine model of DD was induced by aortic banding. A significant correlation was found between plasma CTGF and E/e′ in DHF patients. The severity of cardiac fibrosis evaluated by CMRI also correlated with CTGF. In the cell model, stretch increased secretion of CTGF from cardiomyocytes. In the canine model, myocardial tissue CTGF expression and fibrosis significantly increased after 2 weeks of aortic banding. Notably, the expression of CTGF paralleled the severity of LV DD ( r = 0.40, P < 0.001 for E/e') and haemodynamic changes ( r = 0.80, P < 0.001). After adjusting for confounding factors, CTGF levels still correlated with diastolic parameters in both human and canine models (human plasma CTGF, P < 0.001; canine tissue CTGF, P = 0.04). Conclusion Plasma CTGF level correlated with the severity of DD and tissue fibrosis in DHF patients. The mechanism may be through myocardial stretch. Our study indicated that CTGF may serve as an early marker for DHF. [ABSTRACT FROM AUTHOR]

Background: E-selectin is implicated in various inflammatory processes and related disorders. We aimed to investigate the role of SELE-gene genotypes/haplotypes on plasma levels of MMP9 and sE-selectin in Taiwanese individuals. Methods: Five hundred twenty individuals were enrolled. Seven tagging SELE single nucleotide polymorphisms were analyzed. Results: SELE genotypes were found associated with MMP9 and sE-selectin levels. Multivariate analysis identified that the most significant genetic polymorphism (rs5368 genotype) was independently associated with MMP9 levels (P < 0.001). One haplotype (GGAGAGT) was marginally associated with MMP9 levels (P = 0.0490). One SELE SNP, (rs3917406, P = 0.031) was associated with sE-selectin levels after adjusting for MMP9 and sICAM1 levels. Subgroup and interaction analysis revealed association of SELE SNP rs10800469 with sE-selectin levels only in the highest quartile of MMP9 level (P = 0.002, interaction P = 0.023). Haplotype analysis showed one haplotype (AAAAAGC) borderline associated with sE-selectin level (P = 0.0511). Conclusion: SELE genotypes/haplotypes are independently associated with MMP9 and E-selectin levels in Taiwanese individuals. The associations of SELE genotypes/haplotypes with sE-selectin levels are affected by MMP9 levels. [ABSTRACT FROM AUTHOR]

Background: Angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms have been associated with acute coronary syndrome (ACS); however, several controversial results have also been found in different studied populations. This hospital-based, emergency room, case-control study in Taiwan retrospectively investigated 111 ACS patients, and 195 non-coronary subjects as a control group, to study the effects of ACE I/D polymorphism in the most urgent ACS patients. ACE I/D polymorphisms were determined by polymerase chain reaction-based assays and their associations with ACS risk, severity, and sudden cardiac death were determined. Results: The ACE DD genotype was associated with ACS incidence. The DD genotype was associated with a significant 4-fold higher risk of ACS in multivariate analysis (odds ratio (OR) = 4.295; 95% confidence interval (CI): 1.436-12.851, p = 0.009), and a 3.35-fold higher risk of acute myocardial infarction. DD genotype carriers also had more than 3-fold higher risks of stenosis in all the three coronary arteries, left anterior descending artery infarction, and anterior wall infarction. In addition, the DD genotype was also associated with a higher risk of sudden cardiac death (OR = 6.484, 95% CI: 1.036-40.598, p = 0.046). Conclusions: This study demonstrated that the ACE DD genotype is an independent risk factor for ACS, and in particular, for acute myocardial infarction. In addition, the ACE DD genotype is also associated with greater ACS severity and a higher risk of sudden cardiac death. ACE genotyping is recommended for patients with a history of ACS, and more intensive preventive care is suggested for patients with the DD genotype. [ABSTRACT FROM AUTHOR]

Background: Determinants of functional mitral regurgitation (FMR) severity after acute anterior myocardial infarction (MI) remained unclear. Our aim was to: (1) test whether LV dyssynchrony upon real time three-dimensional echocardiography (RT-3DE) is independently associated with FMR severity; and (2) to investigate the role of regional systolic dyssynchrony index (SDI) in identifying FMR severity. Methods: RT-3DE was successfully performed on 64 consecutive patients following acute anterior MI with a narrow QRS complex (<130 ms) and another 30 healthy volunteers. MR severity was assessed using vena contracta method. SDI was derived from the dispersion of the time to minimum regional volume for all 16 LV segments. Multiple linear regression analysis was used to identify the independent relationship between FMR and SDI with and without multivariate adjustment. Results: The mean LV ejection fraction was 49.6% ± 11.9% in the MI group. All regional (except apical) and global SDIs were associated with regional LV remodeling and were significantly correlated with FMR even after multivariate adjustment, with midwall SDI being most strongly associated with MR severity (R2 = 0.55, P < 0.001). Regional midwall SDI superimposed on LV global geometry and mitral leaflet deformation substantially expanded the area under curve in identifying FMR (AUC increased from 0.69 to 0.93, cstatistics: P = 0.041). Conclusions: While both global and regional dyssynchrony following anterior MI were independently related to FMR severity, regional midwall dyssynchrony further added incremental value in predicting FMR severity beyond traditional parameters. This finding provides a new insight into the understanding of FMR after anterior MI and may further potentiate specific therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Admission for an acute heart failure (HF) confers an extremely poor prognosis. We aimed at finding out whether simultaneous assessment of multiple plasma-based biomarkers and Doppler echocardiography could provide complementary information and thus enable clinicians to stratify risk more effectively among patients hospitalized with acute HF; hence, untoward events after discharge avoided. Methods: A comprehensive echocardiographic study and measurements of cardiac troponin I (cTnI), N-terminal pro-B-type natriuretic protein (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) were conducted in 87 patients with symptomatic de novo acute HF or decompensation of chronic HF. Major adverse cardiac events (MACE) regarding cardiac death or hospitalization with worsening HF during a median follow-up period of 191 days were determined. Results: According to the univariate analysis, echocardiographic variables left atrial volume, left atrial volume index, pulmonary artery systolic pressure, E/E′ ratio, and the concentrations of NT-proBNP were significantly related to clinical outcomes (all P-values < 0.05). Cox proportional hazard analysis identified two independent prognostic predictors of MACE: E/E′ ratio and NT-proBNP. Moreover, the combining of plasma level of NT-proBNP with E/E′ ratio provided independent and additional prognostic value in identifying high-risk acute HF patients. Conclusions: These findings reinforce the necessity of combining the heart hemodynamic variable E/E′ ratio and plasma-based neurohormonal biomarker NT-proBNP when clinicians attempt to define the individual risk of patients hospitalized with acute HF. (Echocardiography 2011;28:303-310) [ABSTRACT FROM AUTHOR]

Objectives: Heart-rate corrected QT (QTc) interval predicts cardiovascular mortality or all-cause mortality in the general population. Little is known about the best cut-off value of QTc interval for predicting clinical events in patients with ST-elevation myocardial infarction (STEMI)., Methods: We enrolled 264 patients with STEMI who received measurement of QTc intervals at ER (QTc-ER), on day 2 (QTc-D2), and on day 3 (QTc-D3) of hospitalization. Clinical events, including all-cause death and readmission for heart failure, were followed for 2 years., Results: Prolonged QTc-ER, but not QTc-D2 or QTc-D3, well predicted clinical events with the best cut-off value of 445 ms. Patient with QTc-ER > 445 ms had lower left ventricular ejection fraction at baseline and at 6 months. Kaplan-Meier survival curves showed that the combination of QTc-ER > 445 ms and N-terminal pro-brain natriuretic peptide (NT-pro BNP) > 936 pg/mL was a strong predictor of clinical events (p<0.001). In multivariable Cox regression analysis, the independent predictors of death and heart failure were QTc-ER (p<0.001), log NT-proBNP (p<0.001), diabetes mellitus (p<0.001), history of stroke (p=0.001), and left ventricular end diastolic volume index (p<0.001)., Conclusion: QTc-ER > 445 ms independently predicts clinical events in STEMI, providing incremental prognostic value to established clinical predictors and NT-proBNP.