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Abstract Chronic kidney disease (CKD) is associated with cardiac conduction defects and is a strong risk factor for heart failure. Complete left bundle branch block (cLBBB), a cardiac conduction abnormality, may have an unfavorable effect on ventricular mechanical synchrony and lead to the progression of heart failure. Once heart failure develops, it seems to act together with underlying CKD in a vicious circle. Therefore, this study aimed to explore the influence of CKD in patients with cLBBB by assessing the estimated glomerular filtration rate (eGFR). We examined a hospital-based sample of 416 adult patients with cLBBB from 2010 to 2013. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cox proportional hazard models were used to estimate the hazard ratio for all-cause mortality and cardiovascular mortality. A total of 416 adult patients with a mean age of 71 ± 13 years were enrolled. The median follow-up period was 3.6 years. After adjusting for clinical, electrocardiographic parameters, and medication use, cox regression analysis showed that total mortality was significantly associated with older age (Hazard Ratio (HR) = 1.03, 95% CI = 1.01–1.05, p = 0.002), presence of congestive heart failure (HR = 2.39, 95% CI = 1.63–3.49, p

Abstract Aims Left bundle branch block (LBBB) is associated with an increased risk of adverse outcomes for patients with heart failure. The prognosis of LBBB in patients with a preserved ejection fraction (EF) remains controversial. This study investigated the predictive value of T‐wave discordance for the prognosis of patients with LBBB and preserved or mildly reduced EF. Methods and results We enrolled 707 patients with complete LBBB and left ventricular (LV) EF ≥ 40% observed using electrocardiograms (ECGs) and echocardiograms between January 2010 and December 2018. Their serial ECGs were reviewed during the follow‐up period. The T‐wave pattern was classified as discordant LBBB (dLBBB) or concordant LBBB (cLBBB) according to the 12‐lead ECG T‐wave morphology. The primary outcome was the composite of cardiovascular death or hospitalization for heart failure during a median follow‐up period of 3.1 years. A multivariable Cox regression analysis was used to evaluate the independent predictors of the primary outcome. Patients with dLBBB had more comorbidities, a higher heart rate, a longer QRS and QTc duration, a larger LV end‐systolic volume and left atrial dimension, a lower LVEF, and a higher mitral E/A ratio and E/e′, compared with those with cLBBB. Older age [hazard ratio (HR) = 1.023, 95% confidence interval (CI) = 1.001–1.046, P = 0.023], history of heart failure (HR = 2.440, 95% CI = 1.524–3.905, P = 0.001), chronic kidney disease (HR = 1.917, 95% CI = 1.182–3.110, P = 0.008), larger LV end‐systolic volume (HR = 1.046, 95% CI = 1.017–1.075, P = 0.002), lower LVEF (HR = 0.916, 95% CI = 0.885–0.948, P = 0.001), and presence of dLBBB (HR = 1.63, 95% CI = 1.011–2.628, P = 0.032) were independent predictors of the primary outcome in patients with LBBB and LVEF ≥ 40%. The discordant or concordant T‐wave morphology of LBBB could transform from one subtype to the other in up to 23% of the study population during the follow‐up period, and individuals with persistent or transformed dLBBB faced an increased risk of cardiovascular death or non‐fatal heart failure hospitalization. Conclusions In patients with LBBB and EF ≥ 40%, dLBBB serves as an independent predictor of a higher risk of cardiovascular death or non‐fatal heart failure hospitalization.

Background/purpose: Predictive modeling aids in identifying patients at high risk of adverse events. Using routinely collected data, we report a competing risk prediction model for kidney failure. Methods: A total of 5138 patients with CKD stages 3b–5 were included and randomized into the development and validation cohorts at a ratio of 7:3. The outcome was end-stage kidney disease, defined as the initiation of dialysis or kidney transplantation. All patients were followed-up until December 31, 2020. A Fine and Gray model was applied to estimate the sub-hazard ratio of kidney failure, with death as a competing event. Results: In the development cohort, the mean age was 67.6 ± 13.9 years and 60 % were male. The mean index eGFR and median urinary protein-creatinine ratio (UPCR) were 26.5 ± 12.8 mL/min/1.73 m2 and 1051 mg/g, respectively. The median follow-up duration was 1051 days. The proportion of patients with kidney failure and death was 25.4 % and 14.1 %, respectively. Four models were applied, including eGFR, age, sex, UPCR, systolic and diastolic blood pressure, serum albumin, phosphate, uric acid, haemoglobin, and potassium levels had the best goodness of fit. All models had good discrimination with time-to-event c statistics of 0.89–0.95 in the development cohort and 0.86–0.95 in the validation cohort. The prediction models showed excellent and fairly good calibration at 2 and 5-year risk, respectively. Conclusion: Using real-world data, our competing risk model can accurately predict progression to kidney failure over 2 years in patients with advanced CKD.

Abstract Background Intraoperative hypotension is a common side effect of general anesthesia. Here we examined whether the Hypotension Prediction Index (HPI), a novel warning system, reduces the severity and duration of intraoperative hypotension during general anesthesia. Methods This randomized controlled trial was conducted in a tertiary referral hospital. We enrolled patients undergoing general anesthesia with invasive arterial monitoring. Patients were randomized 1:1 either to receive hemodynamic management with HPI guidance (intervention) or standard of care (control) treatment. Intraoperative hypotension treatment was initiated at HPI > 85 (intervention) or mean arterial pressure (MAP)

Background: Tuberculosis (TB) remains prevalent worldwide, and anti-TB drugs are associated with drug-induced liver injury (DILI). Statins have pleiotropic effects which may decrease inflammation and achieve immunomodulation. However, few studies have investigated the pleiotropic effects of statins on the risk of DILI. The purpose of this study was to investigate whether statins prevent anti-tuberculosis DILI among active TB patients on standard anti-TB drug therapy. Methods: We conducted a hospital-based retrospective cohort study using claims data from the Integrated Medical Database of National Taiwan University Hospital (NTUH-iMD). Patients with a positive TB culture were included. The use of statins was defined as a daily equivalent dose >0.5 mg of pitavastatin. Deterioration in liver function was evaluated according to elevated liver enzyme levels. The primary and secondary endpoints were the DILI and the severe DILI. The prognostic value of statins was evaluated by Kaplan–Meier analysis, and Cox proportional hazards models. Results: A total of 1312 patients with a diagnosis of TB and receiving anti-TB treatment were included. During the study period, 193 patients had the DILI and 140 patients had the severe DILI. Kaplan–Meier analysis showed a significant difference between the usual statin users and controls in the DILI. In multivariable Cox proportional hazards analysis, statins showed a protective effect against the primary and secondary endpoints. In addition, the protective effect of statins showed a dose–response relationship against the DILI. Conclusion: Statin treatment had a protective effect against the risk of anti-TB DILI with a positive dose–response relationship.

Abstract Evidence for the role of electrocardiography or echocardiography in determining left ventricular hypertrophy for the risk of diabetes is still controversial. We aimed to explore whether left ventricular mass, as measured by these methods, is associated with the risk of diabetes in a community population. We recruited 2696 participants aged 35 years or older without diabetes who had undergone screening with electrocardiography and echocardiography. Left ventricular mass index (LVMI) was calculated using a formula, and participants were divided into tertiles based on their LVMI tertiles. During a median follow-up period of median, 8.9 years, a total of 405 participants developed diabetes. The incidence and risk of diabetes significantly increased with higher LVMI tertiles. Multivariate Cox regression analysis demonstrated that individuals in the highest LVMI tertile had a greater likelihood of developing incident diabetes, with a hazard ratio of 1.40 (95% CI 1.06–1.91), even after adjusting related covariates. The highest risk of diabetes was observed in the presence of both the uppermost LVMI tertile and electrocardiographically determined left ventricular hypertrophy for the Chinese population. Left ventricular hypertrophy identified by either electrocardiography or echo may serve as a surrogate marker for identifying the risk of diabetes in clinical practice.

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

Background Several studies have examined the intended effects of pay-for-performance (P4P) programs, yet little is known about the unintended spillover effects of such programs on intermediate clinical outcomes. This study examines the long-term spillover effects of a P4P program for diabetes care.Methods This study uses a nationwide population-based natural experimental design with a 3-year follow-up period under Taiwan’s universal coverage healthcare system. The intervention group consisted of 7688 patients who enrolled in the P4P program for diabetes care in 2017 and continuously participated in the program for three years. The comparison group was selected by propensity score matching (PSM) from patients seen by the same group of physicians. Each patient had four records: one pertaining to one year before the index date of the P4P program and the other three pertaining to follow-ups spanning over the next three years. Generalized estimating equations (GEEs) with difference-in-differences (DID) estimations were used to consider the correlation between repeated observations for the same patients and patients within the same matched pairs.Results Patients enrolled in the P4P program showed improvements in incentivized intermediate clinical outcomes that persisted over three years, including proper control of glycated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDL-C). We found a slight positive spillover effect of the P4P program on the control of non-incentivized triglyceride [TG]). However, we found no such effects on the non-incentivized high-density lipoprotein cholesterol (HDL-C) control.Conclusion The P4P program has achieved its primary goal of improving the incentivized intermediate clinical outcomes. The commonality in production among a set of activities is crucial for generating the spillover effects of an incentive program.

Abstract Background This study aimed to determine whether primary parathyroid cancer patients were associated with increased metabolic and cardiovascular comorbidities in comparison to the general population. Methods We used the National Taiwan Cancer Registry Database to construct a cohort of patients with parathyroid cancer from January 1, 2004, to December 31, 2019. We compared the incidence of hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, coronary heart disease, and heart failure with the general population matched based on a propensity score in a one-to-five fashion. Results A total of 72 parathyroid cancer patients and 360 matched general population (mean age: 55 years; 59% women) were included, with different exclusive numbers for each metabolic and cardiovascular comorbidity cohort. The number of cases based on a total of 2347.7 person-years of observation included 53 deaths, 29 hypertension, 9 diabetes, 13 hyperlipidemia, 10 atrial fibrillation, 18 coronary artery disease, and 13 heart failure. According to multivariate analysis, parathyroid cancer remained significantly associated with diabetes [hazard ratio (HR): 9.28; 95% confidence interval (CI): 1.72–50.07], hyperlipidemia (HR: 5.86; 95% CI: 1.61–21.31), and heart failure (HR: 4.46; 95% CI: 1.18–16.84). Sub-distribution of competing mortality events and subgroup analysis showed robust evidence of metabolic and cardiovascular comorbidities. This national cohort study demonstrated that adult parathyroid cancer patients had a significantly higher incidence of diabetes mellitus, hyperlipidemia, and heart failure than the general population. Conclusions An increased risk of metabolic and cardiac comorbidities among parathyroid cancer patients required great caution.

Objectives: The aim of this study was to investigate the prognostic value of reclassified new type III monomicrobial gram-negative necrotizing fasciitis (NF) and the microbial factors associated with an increased risk of mortality. Methods: This study included 235 NF cases treated at National Taiwan University Hospital. We compared the mortality risk of NF caused by different causal microorganisms and examined the bacterial virulence genes profile and antimicrobial susceptibility pattern associated with an increase in mortality risk. Results: Type III NF (n = 68) had a mortality risk two-fold higher than type I (polymicrobial, n = 64) or type II (monomicrobial gram-positive, n = 79) NF (42.6% vs 23.4% or 19.0%, P = 0.019 and 0.002, respectively). Mortality differed by causal microorganism (Escherichia coli [61.5%], Klebsiella pneumoniae [40.0%], Aeromonas hydrophila [37.5%], Vibrio vulnificus [25.0%], polymicrobial [23.4%], group A streptococci [16.7%], and Staphylococcus aureus [16.2%], in decreasing rank, P

Background The relationship between resting heart rate (RHR) and the risk of end‐stage renal disease (ESRD) among those without cardiovascular disease remains unclear. We aim to establish temporal consistency and elucidate the independent relationship between RHR and the risk of ESRD. Methods and Results This cohort enrolled participants from 476 347 individuals who had taken part in a screening program from 1996 to 2017. We identified 2504 participants who had ESRD, and the median follow‐up was 13 years. RHR was extracted from electrocardiography results, and the study assessed the relationship between RHR and the risk of ESRD using the Cox proportional hazards model. Of the participants, 32.6% had an RHR of 60 to 69 beats per minute (bpm), and 22.2% had an RHR of ≥80 bpm. Participants with an RHR of ≥80 bpm had a higher stage of chronic kidney disease, lower estimated glomerular filtration rate, and more proteinuria than those with an RHR of 60 to 69 bpm. Participants with an RHR of 80 to 89 and ≥90 bpm had a 24% (hazard ratio [HR], 1.24 [95% CI, 1.09–1.42]) and 64% (HR, 1.64 [95% CI, 1.42–1.90]) higher risk of ESRD, respectively. The risk of ESRD remained significantly elevated (HR, 1.32 [95% CI, 1.10–1.58] per 10‐beat increase from 60 bpm) after excluding participants who smoked; had hypertension, diabetes, or hyperlipidemia; or were overweight. Conclusions An RHR of ≥80 bpm is significantly associated with an increased risk of ESRD. These results suggest that RHR may serve as a risk factor for kidney disease in individuals without established cardiovascular disease risk factors.

Abstract Background Single-nucleotide polymorphisms (SNPs) in various genetic loci are associated with childhood obesity; however, their influence on adolescent growth patterns has rarely been explored. This study investigated whether genetic variants could predict tri-ponderal mass index (TMI)-derived growth trajectories and the interaction between genetic and dietary factors. Methods We conducted Taiwan Puberty Longitudinal Study, a prospective cohort that recruited 1,135 children since 2018. Anthropometric measurements were recorded every three months, while dietary nutrition assessment and biological sampling for genotyping were collected during the first visit. TMI growth trajectory groups were identified using growth mixture modeling. A multinomial logistic regression model for different growth trajectories was used to examine the effect of candidate SNPs, and the most related SNPs were used to establish the genetic risk score. We then explored the effect of the genetic risk score in subgroup analysis according to dietary calories and different dietary consumption patterns. Results Three TMI-based growth trajectory groups were identified among adolescents. The “increased weight” trajectory group accounted for approximately 9.7% of the participants. FTO/rs7206790 was associated with the increased weight growth trajectory after adjusting for the baseline TMI and other correlated covariates (OR: 2.13, 95% CI: 1.08–4.21). We generated the genetic risk score using 4 SNPs (FTO/rs7206790, ADCY9/rs2531995, TFAP2B/rs4715210, and TMEM18/rs6548238) and selected the threshold of 10 points to define risk categories. There were 11.66% and 3.24% of participants belonged to the increased weight trajectory in high- and low-risk groups, respectively; and the predictive ability of the genetic risk score was notable among low calories intake participants (OR: 1.90, 95% CI: 1.18–3.05 vs. OR: 1.17, 95% CI: 0.78–1.75 in high calories intake group). Conclusion Our results offer a new perspective on the genetic and dietary basis of changes in adolescent obesity status. Individualized interventions for obesity prevention may be considered among high-risk children.

Abstract Background The associations with cancer and cardiovascular diseases (CVD) had inconsistent results. The study aimed to investigate the risk of cardiovascular diseases (CVD) between populations with and without cancer. Methods Patients with common cancers in Taiwan were enrolled in the study between 2007 and 2018 using the Taiwan Cancer Registry. We focused on colorectal cancer, women’s breast cancer, lung cancer, liver cancer, oral cancer, prostate cancer, and thyroid cancers. The study endpoint was fatal and non-fatal CVD, which was defined as ischemic heart disease and ischemic stroke according to the National Health Insurance Research Database. We compared the risk of CVD between patients with cancer and age- and sex-matched (1:1 ratio) participants who did not have cancer or CVD. Multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained from Cox regression analysis. To evaluate the chronological trend, we estimated the HRs and 95% CI yearly since the diagnosis. Results Among the 552,485 cancer patients (mean age, 60.6 years; women, 47.7%) during the median follow-up period of 4.1 years, 32,634 cases of fatal and non-fatal CVD were identified. Compared with that noted in the non-cancer population, the overall fully adjusted HR with 95% CI was 1.28 (1.25, 1.30) in the cancer population. The CVD risk was the highest in the first year, the adjusted HR with 95% CI was 2.31 (2.23, 2.40), and this risk decreased yearly. Conclusions Patients with cancer had a significantly higher risk of fatal or non-fatal CVD. The risk was the highest in the first year since diagnosis and decreased yearly.

Abstract Treatment with levothyroxine and radioiodine contribute alternative cardiovascular function in adults with thyroid cancer. The risks of long-term cardiovascular conditions among thyroid cancer patients is unknown. This study aimed to compare the incidence of coronary heart disease (CHD), ischemic stroke (IS), and atrial fibrillation (AF) among adults with thyroid cancer with that of the general population, especially when stratified by age (

BackgroundKnowledge of the risk of death in patients with dementia is essential for planning preventive strategies. This study aimed to evaluate the effect of atrial fibrillation (AF) on death risks and other factors associated with death in patients with dementia and AF.MethodsWe conducted a nationwide cohort study using Taiwan's National Health Insurance Research Database. We identified subjects with dementia diagnosed for the first time and AF diagnosed concomitantly between 2013 and 2014. Subjects under the age of 18 years were excluded. Age, sex, and CHA2DS2-VASc scores were 1: 4 matched for AF patients (N = 1,679) and non-AF controls (N = 6,176) using the propensity score technique. The conditional Cox regression model and competing risk analysis were applied. The risk of mortality was tracked till 2019.ResultsAF history was associated with higher risks of all-cause death (hazard ratio [HR]: 1.208; 95% confidence interval [CI]: 1.142–1.277) and cardiovascular death (subdistribution HR: 1.210; 95% CI: 1.077–1.359) in dementia patients than patients without a diagnosis of AF. For patients with both dementia and AF, they had a higher risk of death due to higher age, diabetes mellitus, congestive heart failure, chronic kidney disease, and prior stroke. Anti-arrhythmic drugs and novel oral anticoagulants significantly reduced the risk of death in patients with AF and dementia.ConclusionThis study found that AF is a risk factor for mortality in patients with dementia and explored several risk factors for AF-related mortality. This study highlights the importance of controlling AF especially in patients with dementia.

ObjectiveTo determine the association between thyroid cancer and coronary artery disease, atrial fibrillation, cerebrovascular disease, and cardiovascular disease mortality.MethodsThe PubMed, Embase, and Cochrane Library databases were searched for eligible studies from inception to September 22, 2022. Keywords included “thyroid cancer”, “atrial fibrillation”, “coronary artery disease”, “cerebrovascular disease”, and “mortality”. Primary outcomes included the incidence of coronary artery disease, cerebrovascular disease, atrial fibrillation, and cardiovascular disease mortality among patients with thyroid cancer. Secondary outcomes included cardiovascular disease events among those with thyroid cancer that received or did not receive radioactive iodine or lenvatinib. Estimates were pooled using fixed- and random-effects meta-analysis.ResultsA total of 771,220 patients who underwent thyroidectomy in 15 studies were included. Risk for cerebrovascular disease (risk ratio [RR] 1.15 [95% confidence interval (CI) 1.10–1.21]) and atrial fibrillation [RR 1.59 (95% CI: 1.45–1.73)] were significantly increased. Risk for coronary artery disease was significantly increased [RR 1.12 (95% CI: 1.08–1.17)] in the common effect model. Cardiovascular disease mortality associated with thyroid cancer was not significant [RR 0.93 (95% CI: 0.59–1.45)]. Radioactive iodine had a neutral effect on cardiovascular disease [RR 1.00 (95% CI: 0.87–1.16)], and there was no beneficial nor harmful effect among different RAI doses.ConclusionsThyroid cancer was significantly associated with a higher risk for cerebrovascular disease and atrial fibrillation; however, the hazard risk was not different between patients with and without radioactive iodine treatment. Thyroid cancer treatment should be individualized considering the potential harms and benefits to cardiovascular health.

The present study aimed to investigate the relationship between dietary patterns and the risk of type 2 diabetes mellitus (T2DM) among Taiwanese individuals. Data were collected using a nationwide cohort study (2001–15) from the Triple-High Database. Dietary intake was assessed using the twenty-group food frequency questionnaire and used to calculate alternate Mediterranean diet (aMED) and Dietary Approaches to Stop Hypertension (DASH) scores. Principal component analysis (PCA) and partial least-squares (PLS) regression were used to derive dietary patterns, with incident T2DM as the outcome. Multivariable-adjusted hazard ratios and 95 % confidence intervals were calculated using time-dependent Cox proportional hazards (Cox PH) regression analysis, and subgroup analyses were performed. A total of 4705 participants were enrolled in the study, and 995 had newly developed T2DM during the median 5⋅28-year follow-up period (30⋅7 per 1000 person-years). Six dietary patterns were extracted (PCA: Western, prudent, dairy and plant-based; PLS: health-conscious, fish-vegetable and fruit-seafood). The highest aMED score quartile had a 25 % (hazard ratio 0⋅75; 95 % CI 0⋅61, 0⋅92; P = 0⋅039) lower risk of T2DM than the lowest quartile. This association remained significant after adjustment (adjusted hazard ratio 0⋅74; 95 % CI 0⋅60, 0⋅91; P = 0⋅010), and no effect modifier was found for aMED. The DASH scores, PCA and PLS dietary patterns were not significant after adjustment. In conclusion, high adherence to a MED-type dietary pattern by Taiwanese foods was associated with a lower risk of T2DM in the Taiwanese population, regardless of unhealthy lifestyle habits.

AimsTo explore the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RAs) on glycemic control and weight reduction in adults.MethodsDatabases were searched from August 2021 to March 2022. Data were analyzed using mean difference (MD) values with 95% confidence intervals (CIs). Both random-and fixed-effect models were employed. Heterogeneity was explored using pre-specified subgroup analyses and meta-regression. Structural equation modeling fitting was used for the multivariate meta-analysis.ResultsA total of 31 double-blind randomized controlled trials with 22,948 participants were included in the meta-analysis. The MD and 95% CI of the pooled GLP1-RA-induced change in the glycated hemoglobin level was -0.78% (-0.97%, -0.60%) in the random-effects model and -0.45% (-0.47%, -0.44%) in the fixed-effect model, with a high heterogeneity (I2 = 97%). The pooled body weight reduction was -4.05 kg (-5.02 kg, -3.09 kg) in the random-effects model and -2.04 kg (-2.16 kg, -1.92 kg) in the fixed-effect model (I2 = 98%). The standardized pooled correlation coefficient between HbA1c levels and body weight was -0.42. A negative correlation between glycemic control and weight reduction was obtained.ConclusionLong-acting GLP-1 RAs significantly reduced the glycated hemoglobin level and body weight in adults.

Background: Left ventricular mass is a highly heritable disease. Previous studies have suggested common genetic variants to be associated with left ventricular mass; however, the roles of rare variants are still unknown. We performed targeted next-generation sequencing using the TruSight Cardio panel, which provides comprehensive coverage of 175 genes with known associations to 17 inherited cardiac conditions.Methods: We conducted next-generation sequencing using the Illumina TruSight Cardiomyopathy Target Genes platform using the 5% and 95% extreme values of left ventricular mass from community-based participants. After removing poor-quality next-generation sequencing subjects, including call rate

BackgroundMenarche timing may not be directly associated with the risk of coronary artery disease (CAD). Therefore, we investigated the roles of metabolic factors in explaining the effect of age at menarche on CAD risk.MethodsWe identified women with age at menarche and CAD by using three analytical methods: Mendelian randomization (MR), logistic regression analysis, and Cox proportional hazard regression. The first two analyses were performed in the Taiwan Biobank (N = 71,923) study, and the last analysis was performed in the Chin-Shan Community Cardiovascular Cohort study (N = 1,598). We further investigated the role of metabolic factors in mediating the effect of age at menarche on CAD risk by using three complementary methods with mediation analyses.ResultsOne standard deviation of earlier age at menarche was associated with a 2% higher CAD risk [odds ratio = 1.02, 95% confidence interval (CI) = 1.001–1.03] in the MR analysis, an 11% higher risk (odds ratio = 1.11, 95% CI = 1.02–1.21) in the logistic regression analysis, and a 57% higher risk (hazard ratio = 1.57, 95% CI = 1.12–2.19) in the Cox proportional hazard regression. All the analyses consistently supported the role of systolic blood pressure in mediating this effect. The MR results indicated that 29% (95% CI = 26%–32%) of the effect of genetically predicted earlier age at menarche on CAD risk was mediated by genetically predicted systolic blood pressure.ConclusionThe results obtained using different analytical methods suggest that interventions aimed at lowering systolic blood pressure can reduce the cases of CAD attributable to earlier age at menarche.

Abstract Background Chronic inflammation might play a major role in the pathogenesis linking diabetes mellitus (DM) to cognition. In addition, DM might be the main driver of dementia risk. The purpose of the present study was to evaluate whether inflammation, glycation, or both are associated with the risk of developing all-cause dementia (ACD). Methods A nationwide population-based cohort study was conducted with 4113 participants. The data were obtained from the Taiwanese Survey on Prevalence of Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH) in 2007, which was linked with the Taiwan National Health Insurance Research Database (NHIRD). The markers of inflammation, expressed as hs-CRP, and glycation, presented as HbA1c, were measured. High levels of hs-CRP and HbA1c were defined as values greater than or equal to the 66th percentile. Developed ACD was identified based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Results During 32,926.90 person-years, 106 individuals developed ACD in up to 8 years of follow-up. The study participants were separated into four categories by the top tertiles of hs-CRP and HbA1c based on the 66th percentile: high levels of both hs-CRP and HbA1c, only high levels of hs-CRP, only high levels of HbA1c, and non-high levels of hs-CRP nor HbA1c. Those who with a high level of only hs-CRP had the higher hazard for developing ACD (adjusted HR = 2.58; 95% CI = 1.29 ~ 5.17; P = 0.007), followed by the group with a high level of only HbA1c (adjusted HR = 2.52; 95% CI = 1.34 ~ 4.74; P = 0.004) and the group with high levels of both hs-CRP and HbA1c (adjusted HR = 2.36; 95% CI = 1.20 ~ 4.62; P = 0.012). Among those aged less than 65 years, hs-CRP was the only significant predictor of ACD risk (P = 0.046), whereas it did not yield any significant result in the elderly. Conclusions A higher risk of developing ACD was found not only in patients with high levels of inflammation but also high levels of glycated hemoglobin. Future studies should focus on the clinical implementation of hs-CRP or HbA1c to monitor cognitive deficits.

Abstract The protective effect of different healthy lifestyle scores for the risk of cardiovascular disease (CVD) was reported, although the comparisons of performance were lacking. We compared the performance measures of CVDs from different healthy lifestyle scores among Taiwanese adults. We conducted a nationwide prospective cohort study of 6042 participants (median age 43 years, 50.2% women) in Taiwan’s Hypertensive, Hyperglycemia and Hyperlipidemia Survey, of whom 2002 were free of CVD at baseline. The simple and weighted the Mediterranean diet related healthy lifestyle (MHL) scores were defined as a combination of normal body mass index, Mediterranean diet, adequate physical activity, non-smokers, regular healthy drinking, and each dichotomous lifestyle factor. The World Cancer Research Fund and American Institute for Cancer Research cancer prevention recommended lifestyle and Life's Simple 7 following the guideline definition. The incidence of CVD among the four healthy lifestyle scores, each divided into four subgroups, was estimated. During a median 14.3 years follow-up period, 520 cases developed CVD. In the multivariate-adjusted Cox proportional hazard models, adherence to the highest category compared with the lowest one was associated with a lower incidence of CVD events, based on the simple (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.2–0.94) and weighted MHL scores (HR 0.44, 95% CI 0.28–0.68). Additionally, age played a role as a significant effect modifier for the protective effect of the healthy lifestyle scores for CVD risk. Specifically, the performance measures by integrated discriminative improvement showed a significant increase after adding the simple MHL score (integrated discriminative improvement: 0.51, 95% CI 0.16–0.86, P = 0.002) and weighted MHL score (integrated discriminative improvement: 0.38, 95% CI 0.01–0.74, P = 0.021). We demonstrated that the healthy lifestyle scores with an inverse association with CVD and reduced CVD risk were more likely for young adults than for old adults. Further studies to study the mechanism of the role of lifestyle on CVD prevention are warranted.

Abstract Background Blood lipids are essential components for cellular growth. An inverse association between serum lipid levels and risk of cancer has led to a controversy among previous studies. The aim of this prospective cohort study was to investigate the association between blood lipids change and risk of cancer incidence. Methods A cohort of 4130 Taiwanese adults from the Taiwanese Survey on the Prevalence of Hypertension, Hyperglycemia, and Hyperlipidemia database underwent repeated examinations in 2002 and 2007. Six groups were established based on the combined baseline (lower/higher) and interval change (decreasing/stable/increasing) in plasma lipid levels. Multivariable Cox proportional hazard model was used to investigate the relationship between lipids change and all-cause cancer incidence. Results Two hundred and forty cancer events developed over a median follow-up of 13.4 years. Comparing these with individuals with decreasing lower-baseline lipid levels, cancer risk reduction was demonstrated in those with increasing lower-baseline total cholesterol (adjusted hazard ratio [aHR], 0.48; 95% confidence interval [CI], 0.27 to 0.85), low-density lipoprotein cholesterol (LDL-C; aHR, 0.56; 95% CI, 0.35 to 0.92), and non–high-density lipoprotein cholesterol (non-HDL-C) (aHR, 0.54; 95% CI, 0.31 to 0.92) levels. A decreased risk for cancer incidence also presented in participants with stable lower-baseline, decreasing and increasing higher-baseline LDL-C levels, and with decreasing and stable higher-baseline non-HDL-C levels. Conclusions The interval decline in lower-baseline total cholesterol, LDL-C, and non-HDL-C levels was linked to a higher risk for all-cause cancer incidence. More attention to a potential cancer risk may be warranted for an unexplained fall in serum lipids.

Objectives To assess the cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients without diabetes.Methods We searched PubMed, MEDLINE, Embase and Cochrane Library for publications up to 17 August 2022. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Random-effects meta-analyses were performed to pool effect measures across studies. Risk ratios (RRs) with 95% CIs are expressed for composite cardiovascular outcome of cardiovascular death or hospitalisation for heart failure, cardiovascular death, hospitalisation for heart failure, all-cause mortality and composite renal outcome of ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage kidney disease or renal death. Annual rate of change in eGFR is expressed as the mean difference with 95% CI.Results We identified four trials with 8927 patients with heart failure or chronic kidney disease (CKD). Compared with placebo, SGLT2 inhibitors showed favourable effects on the composite cardiovascular outcome (RR: 0.79, 95% CI: 0.71 to 0.87; moderate certainty), cardiovascular death (0.85, 0.74 to 0.99; moderate certainty), hospitalisation for heart failure (0.72, 0.62 to 0.82; moderate certainty), the composite renal outcome (0.64, 0.48 to 0.85; low certainty) and the annual rate of change in eGFR (mean difference: 0.99, 0.59 to 1.39 mL/min/1.73 m2/year; moderate certainty), while there was no significant difference in all-cause mortality (0.88, 0.77 to 1.01; very low certainty). Moderate certainty evidence indicated that SGLT2 inhibitors reduced the risk of serious adverse events and acute renal failure. Low certainty evidence suggested that SGLT2 inhibitors increased the risk of urinary tract infection and genital infection, while there were no differences in discontinuation due to adverse events, amputation, fracture, hypoglycaemia, ketoacidosis or volume depletion.Conclusions Evidence of low to moderate certainty suggests that SGLT2 inhibitors provide cardiorenal benefits but have increased risk for urinary tract infection and genital infection in patients without diabetes and with heart failure or CKD.PROSPERO registration number CRD42021239807.

Abstract The prognosis of out of cardiac arrest is poor and most cardiac arrest patients suffered from the non-shockable rhythm especially in patients without pre-existing cardiovascular diseases and medication prescription. Beta-blocker (ß-blocker) therapy has been shown to improve outcomes in cardiovascular diseases such as heart failure, ischemia related cardiac, and brain injuries. Therefore, we investigated whether prior ß-blockers use was associated with reduced mortality in patients with cardiac arrest and non-shockable rhythm. We conducted a population-based retrospective cohort study using multivariate propensity score–based regression to control for differences among patients with cardiac arrest. A total of 104,568 adult patients suffering a non-traumatic and non-shockable rhythm cardiac arrest between 2005 and 2011 were identified. ß-blocker prescription at least 30 days prior to the cardiac arrest event was defines as the ß-blockers group. We chose 12.5 mg carvedilol as the cut-off value and defined greater or equal to carvedilol 12.5 mg per day and its equivalent dose as high-dose group. After multivariate propensity score–based logistic regression analysis, patients with prior ß-blockers use were associated with better 1-year survival [adjusted odds ratio (OR), 1.15, 95% confidence interval (CI) 1.01–1.30; P = 0.031]. Compared to non-ß-blocker use group and prior low-dose ß-blockers use group, prior high-dose ß-blockers use group was associated with higher mechanical ventilator wean success rate (adjusted OR 1.19, 95% CI 1.01–1.41, P = 0.042). In conclusion, prior high dose ß-blockers use was associated with a better 1-year survival and higher weaning rate in patients with non-shockable cardiac arrest.

Abstract Background Patients with diabetic mellitus (DM) and chronic kidney disease (CKD) are at an increased risk of urinary tract infection (UTI) due to their altered immunological integrity. These patients are similarly prone to developing frailty, a state of cumulative health deficits involving multiple domains and leading to adverse outcomes. Whether frailty predisposes affected individuals to UTI among patients with DM and CKD remains unclear. Methods A population-based cohort of patients with DM and CKD (n = 79,887) were assembled from the Longitudinal Cohort of Diabetes Patients, with their baseline frailty status measured by a modified FRAIL scale. We analyzed their risk of developing UTI depending on their severity of frailty, after accounting demographic profiles, lifestyle factors, comorbidities, concurrent medications, and major interventions. A secondary analysis focused on the risk of urosepsis related to frailty. Results Among all participants, 36.1 %, 50.3 %, 12.8 %, and 0.8 % did not have or had 1, 2, and ≥ 3 FRAIL items, respectively, at baseline. After 3.51 years, 11,175 UTI events occurred. Kaplan-Meier analysis showed that participants with DM, CKD and an increasing number of FRAIL items had successively higher incidence of UTI than those without any FRAIL items (log rank p

Abstract Background Chronic kidney disease (CKD) introduces an increased cardiovascular risk among patients with diabetes mellitus (DM). The risk and tempo of cardiovascular diseases may differ depending upon their type. Whether CKD differentially influences the risk of developing each cardiovascular morbidity in patients with newly diagnosed DM remains unexplored. Methods We identified patients with incident DM from the Longitudinal Cohort of Diabetes Patients (LCDP) cohort (n = 429,616), and uncovered those developing CKD after DM and their propensity score-matched counterparts without. After follow-up, we examined the cardiovascular morbidity-free rates of patients with and without CKD after DM, followed by Cox proportional hazard regression analyses. We further evaluated the cumulative risk of developing each outcome consecutively during the study period. Results From LCDP, we identified 55,961 diabetic patients with CKD and matched controls without CKD. After 4.2 years, patients with incident DM and CKD afterward had a significantly higher risk of mortality (hazard ratio [HR] 1.1, 95% confidence interval [CI] 1.06–1.14), heart failure (HF) (HR 1.282, 95% CI 1.19–1.38), acute myocardial infarction (AMI) (HR 1.16, 95% CI 1.04–1.3), and peripheral vascular disease (PVD) (HR 1.277, 95% CI 1.08–1.52) compared to those without CKD. The CKD-associated risk of mortality, HF and AMI became significant soon after DM occurred and remained significant throughout follow-up, while the risk of PVD conferred by CKD did not emerge until 4 years later. The CKD-associated risk of ischemic, hemorrhagic stroke and atrial fibrillation remained insignificant. Conclusions The cardiovascular risk profile among incident DM patients differs depending on disease type. These findings can facilitate the selection of an optimal strategy for early cardiovascular care for newly diagnosed diabetic patients.

Abstract High baseline atherogenic lipid level has been an established risk factor for the risk of cardiovascular events. Evidence concerning the role of lipid changes in cardiovascular and death risks are inconclusive. A cohort study was conducted based on the Taiwanese Survey on Hypertension, Hyperglycemia, and Hyperlipidemia (n = 4072, mean 44.8 years, 53.5% women) assessing lipid levels of the participants repeatedly measured in 2002 and 2007. Combined baseline and changes in lipid levels were classified into four groups—stable or decreasing lipid changes and increasing lipid changes with low- and high-risk baseline lipid levels. Developing cardiovascular events (n = 225) and all-cause deaths (n = 345) were ascertained during a median follow-up of 13.3 years. Participants with increasing and higher total cholesterol level were more likely to develop cardiovascular risks. Similar patterns for cardiovascular events were observed across other lipid profile changes. However, participants with increasing total cholesterol, LDL-C, and non-high-density lipoprotein cholesterol (non-HDL-C) levels were more likely to be at a lower risk for all-cause deaths. Baseline and changes in total cholesterol, triglycerides, and LDL-C levels were positively associated with the risk of cardiovascular diseases, whereas baseline and changes in total cholesterol and LDL-C and non-HDL-C levels were inversely associated with all-cause deaths.

Associations between of omega-3 fatty acids and mortality are not clear. Here the authors report that, based on a pooled analysis of 17 prospective cohort studies, higher blood omega-3 fatty acid levels correlate with lower risk of all-cause mortality.

Quantitative EEG (qEEG) delineates complex brain activities. Global field synchronization (GFS) is one multichannel EEG analysis that measures global functional connectivity through quantification of synchronization between signals. We hypothesized that preservation of global functional connectivity of brain activity might be a surrogate marker for good outcome in sudden cardiac arrest (SCA) survivors. In addition, we examined the relation of phase coherence and GFS in a mathematical approach. We retrospectively collected EEG data of SCA survivors in one academic medical center. We included 75 comatose patients who were resuscitated following in-hospital or out-of-hospital nontraumatic cardiac arrest between 2013 and 2017 in the intensive care unit (ICU) of National Taiwan University Hospital (NTUH). Twelve patients (16%) were defined as good outcome (GO) (CPC 1–2). The mean age in the GO group was low (51.6 ± 15.7 vs. 68.1 ± 12.9, p < 0.001). We analyzed standard EEG power, computed EEG GFS, and assessed the cerebral performance category (CPC) score 3 months after discharge. The alpha band showed the highest discrimination ability (area under curve [AUC] = 0.78) to predict GO using power. The alpha band of GFS showed the highest AUC value (0.8) to predict GO in GFS. Furthermore, by combining EEG power + GFS, the alpha band showed the best prediction value (AUC 0.86) in predicting GO. The sensitivity of EEG power + GFS was 73%, specificity was 93%, PPV was 0.67%, and NPV was 0.94%. In conclusion, by combining GFS and EEG power analysis, the neurological outcome of the nontraumatic cardiac arrest survivor can be well-predicted. Furthermore, we proved from a mathematical point of view that although both amplitude and phase contribute to obtaining GFS, the interference in phase variation drastically changes the possibility of generating a good GFS score.

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are potent LDL-C lowering agents. However, few head-to-head studies evaluated the efficacy on the lowering in other atherogenic apolipoproteins and safety of PCSK9 inhibitors at different dosages as an add-on statins therapy in hypercholesterolemia patients.Methods: This study is a systematic review and network meta-analysis of randomized control trials to compare the efficacy of lipid reduction and adverse events of PCSK9 inhibitors in statin-treated hypercholesterolemia patients. PubMed, EMBASE, and Cochrane Library databases were searched till April 20, 2021, for randomized controlled trials. Random-effect network meta-analyses were undertaken to compare the differences in the percent reduction in low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) [Lp(a)] levels and the risk of AEs among different PCSK9 inhibitors.Results: A total of 22 articles with 42,786 patients were included. The lipid reductions in LDL-C, ApoB, and Lp(a) with add-on PCSK9 inhibitors vs. placebo in statin-treated patients across all trials were 50–63%, 43–52%, and 23–31%, respectively. Evolocumab 140 mg Q2W was ranked the best among all treatment strategies for lowering LDL-C, ApoB, and Lp(a) levels, and the treatment difference was 68.05% (95% confidence interval (CI), 62.43% to 73.67) in LDL-C reduction, 54.95% (95% CI, 49.55% to 60.35%) in ApoB reduction, and 34.25% (95% CI, 27.59% to 40.91%) in Lp(a) reduction compared with the placebo. No significant risk difference of adverse events between PCSK9 inhibitors and placebo was found.Conclusion: PCSK9 inhibitors showed a significant effect on the reduction in LDL-C, ApoB, and Lp(a) levels in statin-treated patients. Evolocumab 140 mg Q2W showed significantly larger degrees of LDL-C, ApoB, and Lp(a) reduction.

Abstract Few studies quantify a cascade of dynamic transitions on the detailed components of metabolic syndrome (MetS) and subsequent progressions to cardiovascular disease (CVD) and its death. A total of 47,495 subjects repeatedly attending a community-based integrated screening program in Taiwan were recruited. The refined MetS-related classification (RMRC) in relation to five criteria of MetS was defined as free of metabolic disorder (FMD, none of any criteria), mild metabolic disorder (MMD, 1–2 criteria) and MetS. A multistate Markov model was used for modelling such a multistate process. The estimated progression rate from FMD to MMD was 44.82% (95% CI 42.95–46.70%) whereas the regression rate was estimated as 29.11% (95% CI 27.77–30.45%). The progression rate from MMD to MetS was estimated as 6.15% (95% CI 5.89–6.42%). The estimated annual incidence rates of CVD increased with the severity of RMRC, being 1.62% (95% CI 1.46–1.79%) for FMD, 4.74% (95% CI 4.52–4.96%) for MMD, to 20.22% (95% CI 19.52–20.92%) for MetS. The estimated hazard rate of CVD death was 6.1 (95% CI 4.6–7.7) per thousand. Elucidating the dynamics of MetS-related transition and quantifying the incidence and prognosis of CVD provide a new insight into the design and the evaluation of intervention programs for CVD.

Background Long-term dietary phosphorus excess influences disturbances in mineral metabolism, but it is unclear how rapidly the mineral metabolism responds to short-term dietary change in dialysis populations. Methods This was a post hoc analysis of a randomized crossover trial that evaluated the short-term effects of low-phosphorus diets on mineral parameters in hemodialysis patients. Within a 9-day period, we obtained a total of 4 repeated measurements for each participant regarding dietary intake parameters, including calorie, phosphorus, and calcium intake, and markers of mineral metabolism, including phosphate, calcium, intact parathyroid hormone (iPTH), intact fibroblast growth factor 23 (iFGF23), and C-terminal fibroblast growth factor 23 (cFGF23). The correlations between dietary phosphorus intake and serum mineral parameters were assessed by using mixed-effects models. Results Thirty-four patients were analyzed. In the fully adjusted model, we found that an increase in dietary phosphorus intake of 100 mg was associated with an increase in serum phosphate of 0.3 mg/dL (95% confidence intervals [CI], 0.2–0.4, p

Abstract To determine the association between combined lifestyle factors, including healthy diet, moderate alcohol consumption, non-smoking, physical activity, and optimal weight, and cardiovascular disease (CVD) risk among younger and older adults. We conducted a literature search using PubMed, EMBASE, Cochrane Library, and EBSCO databases up to November 30, 2019 and performed dose–response analysis, subgroup analysis and meta-regression with odds ratios and 95% confidence intervals (CIs). Twenty cohort studies involving 1,090,261 participants with 46,288 cardiovascular events and mean follow-up duration of 12.33 years were included. Compared with the group with the lowest number of healthy lifestyle factors, the group with the highest number had lower CVD risk [pooled hazard ratio, 0.37 (95% CI 0.31–0.43)]. With age as an effect modifier, the lifetime risk of CVD was 0.31 (95% CI 0.24–0.41) at age 37.1–49.9 years, 0.36 (95% CI 0.30–0.45) at age 50.0–59.9 years and 0.49 (95% CI 0.38–0.63) at age 60.0–72.9 years. The hazard ratio of CVD significantly increased from 37.1 to 72.9 years of age [slope in multivariate meta-regression: 0.01 (95% CI

Abstract Background Cardiovascular disease is the leading cause of morbidity and mortality with incidence rates of 5–10 per 1000 person-years, according to primary prevention studies. To control hyperlipidemia—a major risk factor of cardiovascular disease—initiation of lipid-lowering therapy with therapeutic lifestyle modification or lipid-lowering agent is recommended. Few systematic reviews and meta-analyses are available on lipid-lowering therapy for the primary prevention of cardiovascular diseases. In addition, the operational definitions of intensive lipid-lowering therapies are heterogeneous. The aim of our study was to investigate whether intensive lipid-lowering therapies reduce greater cardiovascular disease risks in primary prevention settings. Methods MEDLINE, EMBASE, and Cochrane Library databases were searched from inception to March 2019 for randomized controlled trials. We used random effects model for overall pooled risk ratio (RR) estimation with cardiovascular events of interest and all-cause mortality rate for the intensive lipid-lowering group using the standard lipid-lowering group as the reference. The Cochrane Risk of Bias Tool was used for quality assessment. Results A total of 18 randomized controlled trials were included. The risk reductions in cardiovascular outcomes and all-cause mortality associated with more intensive vs. standard lipid-lowering therapy across all trials were 24 and 10%, respectively (RR 0.76, 95% confidence interval 0.68–0.85; RR 0.90, 95% confidence interval 0.83–0.97); however, the risk reduction varied by baseline LDL-C level in the trial. A greater risk reduction was noted with higher LDL-C level. Intensive lipid-lowering for coronary heart disease protection was more pronounced in the non-diabetic populations than in the diabetic populations. Conclusions More intensive LDL-C lowering was associated with a greater reduction in risk of total and cardiovascular mortality in trials of patients with higher baseline LDL-C levels than less intensive LDL-C lowering. Intensive lipid-lowering was associated with a significant risk reduction of coronary heart disease and must be considered even in the non-diabetic populations.

Background/purpose: Nuclear imaging, including gallium scintigraphy and fluorodeoxyglucose (FDG) positron emission tomography (PET), has been widely used to identify focus of infection in fever of unknown origin. However, little is known about its role in critically ill patients, who are usually with multiple inflammatory foci and unable to tolerate long image acquisition time. This systematic review aimed to evaluate the diagnostic performance of FDG PET for suspected infection in critically ill patients. Methods: PubMed and Embase were searched up to July 24th, 2019 to identify studies evaluating the diagnostic performance of FDG PET for finding infection focus in critically ill patients following the PRISMA guidelines. The bivariate mixed-effects model was used to pool the measure for diagnostic performance. Publication bias was evaluated by Deeks' method. Results: A total of 4 studies with 87 patients were included. All the four studies evaluated FDG PET. Majority of the patients were either mechanically ventilated (76%) or shocked requiring vasopressors (61%). Test and transportation related adverse events were rare (2%). The summary sensitivity and specificity were 0.94 (95% CI, 0.79–0.99) and 0.66 (95% CI, 0.45–0.83), respectively. The AUC for summary ROC curve was 0.83. Conclusion: FDG PET was a very sensitive tool with acceptable specificity for detecting the origin of infection in critically ill patients. However, current available studies have limitation in evaluating safety issue. Further research should investigate both benefit and risk of doing this test for this group of vulnerable patients.

Background: The cardiac manifestations of late-onset hereditary transthyretin amyloidosis with p.A97S variant have not been extensively studied, and the prognostic factors remain unclear. Methods: The clinical profile, echocardiography, and ECG of patients diagnosed with ATTR p.A97S polyneuropathy between 2000 and 2016 were retrospectively collected. 67 patients with ATTR p.A97S were collected. Results: A total of 82% of patients met the criteria for left ventricular (LV) hypertrophy. Reduced global longitudinal strain (GLS) was noted in 42.1% of patients, and 14% of patients had a relative apical sparing pattern. A low voltage pattern in the ECG was observed in 31.3% of patients, while 64.2% presented with a pseudoinfarction pattern. End-systolic LV inner dimension (HR: 2.25 (95% CI: 1.01–5.01), p = 0.048), reduced GLS (HR: 5.26 (1.08–25.0), p = 0.039), relative apical longitudinal strain (RALS>1, HR: 8.57 (1.69–43.3), p = 0.009), increased E/A ratio (HR: 6.51 (1.17–36.4), p = 0.033), and increased QRS duration (HR: 1.02 (1.00–1.04), p = 0.05) were correlated with reduced survival in univariate analysis. Multivariate analysis revealed reduced RALS was significantly correlated with reduced survival (HR: 13.00 (1.81–93.45), p = 0.011). Conclusion: Our findings reveal that ATTR p.A97S is a cardiomyopathy as well as a polyneuropathic syndrome. Routine use of more contemporary echocardiographic techniques are recommended to identify cardiac amyloidosis and provide prognostic information. Keywords: Hereditary transthyretin amyloidosis, Familial amyloidotic polyneuropathy, p.A97S, Global longitudinal strain

Background: Necrotizing fasciitis (NF) is a life-threatening soft tissue infection with low incidence that requires prompt surgery. In the initial stage, it is difficult to distinguish NF and cellulitis, and limited population-based reports are available. Methods: We queried inpatient data sets of National Health Institute Research Database in Taiwan from 2002 to 2011 for all patients with diagnoses of NF. Of them, only patients who underwent surgeries and had been admitted to intensive care units were included as the study group. Age and gender-matched patients with admission diagnoses of cellulitis were enrolled in a ratio of 1:4 as the control group. We calculated annual incidence, mortality rate, risk factors and predictors of mortality of NF. Results: The study group consisted of 7391 NF patients. Among them, 4715 patients (64%) were man and 2676 (36%) were women. The overall annual incidence of NF was 3.26 hospitalizations per 100,000 person-years, which rose with age with male predominance. The in-hospital mortality rate, which also rose with age, was 32.2%. Diabetes mellitus (adjusted odds ratio, 2.93; 95% confidence interval, 2.77-3.11; P value < 0.0001), alcoholism (2.64; 2.27-3.08; P

Background: Valve replacement is associated with worse outcomes in individuals who have end-stage renal disease (ESRD) and require a long-term renal replacement therapy. Prosthetic valve selection in patients with ESRD has remained controversial.Objective: We aimed to investigate long-term outcomes of mechanical and bioprosthetic valve replacement in individuals with ESRD.Methods: We conducted a population-based retrospective cohort study using data obtained from the Taiwan National Health Insurance Research Database. In total, 10,202 patients, including 912 ESRD and 9,290 non-ESRD patients, were selected after a 1:1 propensity-score matching based on the type of prosthetic valve used. The long-term mortality outcomes were then analyzed.Results: During a median follow-up period of 59.6 months, the Kaplan–Meier survival analysis revealed that ESRD patients who underwent mechanical valve replacement had higher rates of all-cause mortality and CV deaths than those who underwent bioprosthetic valve replacement (Log-rank test, p = 0.03 and 0.02, respectively). Multivariable regression analyses demonstrated that ESRD patients who underwent bioprosthetic valve replacement had lower rates of all-cause mortality (p < 0.001, hazard ratio: 0.88, 95% confidence interval: 0.82–0.93) and cardiovascular (CV) death (p < 0.001, hazard ratio: 0.83, 95% confidence interval: 0.76–0.90) than those who had mechanical valve replacement.Conclusion: Bioprosthetic valve replacement is significantly associated with lower rates of all-cause mortality and CV death in the ESRD population.

Background: The aim of this study was to determine whether, and if so how, attenuation correction (AC) improves the diagnostic performance of myocardial perfusion imaging (MPI) in different coronary artery-supplied territories, using coronary angiography as the reference standard.Methods: PubMed and EMBASE were searched until December 2020 for studies evaluating AC MPI for the diagnosis of coronary artery disease (CAD) with vessel-based data. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. For each study, the sensitivity, specificity, diagnostic odds ratios and areas under summary receiver operating characteristic curves (AUC) with 95% confidence intervals were calculated to determine the diagnostic accuracy of AC compared to non-AC MPI. A bivariate mixed-effects model was used to pool the data. Subgroup analyses considering the type of radiotracer and type of AC were performed.Results: A total of 264 articles were screened, of which 22 studies (2,608 patients) were enrolled. Significant improvements in specificity [0.78 vs. 0.58 in overall CAD, 0.87 vs. 0.61 in right coronary artery (RCA)] and diagnostic odds ratios (16 vs. 8 in overall CAD, 18 vs. 7 in RCA) after AC were shown in overall CAD at a patient level and RCA stenosis. Improvements in AUC were also noted. MPI had a similar diagnostic performance for detecting left anterior descending and left circumflex coronary artery stenosis with or without AC. There were trends of decreased sensitivity after AC, but none were significant. Diagnostic odds ratio showed significant improvement after AC only in the technetium-99m subgroup.Conclusion: The results of this study suggest that AC should be applied to MPI to improve the diagnosis of CAD regardless of which type of radiotracer, and that AC MPI can improve the specificity of detecting RCA stenosis.

Background This study assessed the associations of metabolic obesity phenotypes with the risk of atrial fibrillation (Afib). Methods This prospective cohort study categorized Taiwanese adults according to their body mass index (BMI) and metabolic health status at baseline. We assigned the participants to the underweight (BMI < 18.5 kg/m2), normal weight (BMI = 18.5–23.9 kg/m2), and overweight/obesity groups (BMI ≥ 24 kg/m2). Metabolically healthy was defined as absence of hypertension, diabetes, and hyperlipidemia and the presence of healthy metabolic profiles. Results In total, 5,742 adults were included. During a median follow-up of 13.7 years, 148 patients developed Afib. Compared to the metabolically healthy normal weight group, the risk of Afib was significantly higher than those in the metabolically unhealthy overweight/obesity (hazard ratio = 2.20, 95% confidence interval [1.12–4.33]) and metabolically unhealthy normal weight groups (HR = 2.64, 95% CI [1.34–5.17]). Additionally, the point estimate suggested a 1.97-fold greater risk among the metabolically healthy overweight/obesity group, although this difference was not significant given the wide confidence interval (HR = 1.97, 95% CI [0.80–4.86]). Conclusion Our results demonstrated the relationships of metabolic health and weight regarding the risk of Afib in Taiwanese adults. The Afib risk among metabolic and obesity phenotypes is associated with a metabolically unhealthy status. A trend toward a higher Afib risk with obesity among metabolically healthy subjects was observed. However, the result was not robust and it still suggested further study.

Background: The clinical significance and outcomes of ventricular tachyarrhythmias (VTa) in patients undergoing valve replacement have rarely been reported.Objective: This study aimed to investigate the incidence and outcome of VTa after surgical valve replacement.Methods: We conducted a population-based retrospective cohort study using data obtained from the Taiwan National Health Insurance Research Database. In total, 10,212 patients were selected after 1:1 propensity-score matching based on the type of prosthetic valve used (mechanical vs. bioprosthetic). Various outcomes during long-term follow-up were analyzed.Results: After a median follow-up period of 59.6 months, the crude incidence rate of VTa after surgical valve replacement was 4.8/1,000 person-years, and the cumulative incidence of VTa persistently increased after surgery. Furthermore, the occurrences of VTa after valve replacement significantly increased the risk of cardiovascular (CV) death (P < 0.001, HR 1.67, 95% CI 1.41–1.96), stroke- (P < 0.001, HR 1.66, 95% CI 1.37–2.01), atrial fibrillation- (P < 0.001, HR 2.80, 95% CI 2.42–3.24), and congestive heart failure-related hospitalization (P < 0.001, HR 2.61, 95% CI 2.30–2.95). Among patients with VTa, all-cause mortality (P = 0.001, HR 0.49, 95% CI 0.32–0.75) and CV death (P = 0.047, HR 0.58, 95% CI 0.34–0.99) in those with implantable cardioverter-defibrillator (ICD) implantation were lower than those without.Conclusion: The crude incidence rate of VTa after surgical valve replacement was 4.8/1,000 person-years, and the cumulative incidence of VTa persistently increased during follow-up. The presence of VTa after surgical valve replacement increases hospitalization and CV death, while ICD implantation reduced the mortality rate in these patients.

Background: Patients with diabetic kidney disease (DKD) are at an increased risk of frailty. The exposure to muscle relaxants frequently leads to adverse effects despite their modest therapeutic efficacy, but whether muscle relaxants predispose users to frailty remains unclear. Methods: Patients with DKD from a population-based cohort, the Longitudinal Cohort of Diabetes Patients, were identified between 2004 and 2011 ( N = 840,000). Muscle relaxant users were propensity score-matched to never-users in a 1:1 ratio based on demographic features, comorbidities, outcome-relevant medications, and prior major interventions. Incident frailty, the study endpoint, was measured according to a modified FRAIL scale. We used Kaplan–Meier analyses and Cox proportional hazard regression to analyze the association between cumulative muscle relaxant use (⩾ 28 days) and the risk of incident frailty. Results: Totally, 11,637 users and matched never-users were enrolled, without significant differences regarding baseline clinical features. Cox proportional hazard regression showed that patients with DKD and received muscle relaxants had a significantly higher risk of incident frailty than never-users [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.04–1.53]. This increase in frailty risk paralleled that in cumulative muscle relaxant dosages (quartile 1 versus 2 versus 3 versus 4, HR 0.91 versus 1.22 versus 1.38 versus 1.45, p = 0.0013 for trend) and in exposure durations (quartile 1 versus 2 versus 3 versus 4, HR 1.12 versus 1.33 versus 1.23 versus 1.34, p = 0.0145 for trend) of muscle relaxants. Conclusion: We found that cumulative muscle relaxant exposure might increase frailty risk. It is prudent to limit muscle relaxant prescription in patients with DKD. Plain language summary Does cumulative muscle relaxant exposure increase the risk of incident frailty among patients with diabetic kidney disease? Background: Frailty denotes a degenerative feature that adversely influences one’s survival and daily function. Patients with diabetes and chronic kidney disease are at a higher risk of developing frailty, but whether concurrent medications, especially muscle relaxants, aggravate this risk remains undefined. Methods: In this population-based study including 11,637 muscle relaxant users and matched never-users with diabetic kidney disease, we used a renowned frailty-assessing tool, FRAIL scale, to assess frailty severity and examined the incidence of frailty brought by muscle relaxant exposure. Results: We found that users exhibited a 26% higher risk of developing incident frailty compared with never-users, and the probability increased further if users were prescribed higher doses or longer durations of muscle relaxants. Conclusion: We concluded that in those with diabetic kidney disease, cumulative muscle relaxant use was associated with a higher risk of incident frailty, suggesting that moderation of muscle relaxant use in this population can be of potential importance.

Background: The stroke risk scoring system for atrial fibrillation (AF) patients can vary considerably based on patients’ status while receiving ablation. This study aimed to demonstrate a novel scoring system for stroke risk stratification based on the status of catheter ablation. Methods: First, 787 patients with AF undergoing ablation were matched according to age, sex, and underlying diseases with the same number of patients not undergoing ablation using the propensity-score (PS)-matched cohort. Multivariate Cox model-derived coefficients were used to construct a simple point-based clinical model using the PS-matched cohort. Thereafter, the novel model (AF-CA-Stroke score) was validated in a nationwide AF cohort. Results: The AF-CA-Stroke score was calculated based on age (point = 5), ablation status (point = 4), prior history of stroke (point = 4), chronic kidney disease (point = 2), diabetes mellitus (point = 1), and congestive heart failure (point = 1). Risk function to predict the 1-, 5-, 10-year absolute stroke risks was reported. The estimated area under the receive operating characteristic curve of the AF-CA-Stroke score in the PS-matched cohort was 0.845 (95% confidence interval: 0.824–0.865) to predict long-term stroke. A validation study showed that discrimination abilities in the AF-CA-Stroke scores were significantly higher than those in the CHADS2/CHA2DS2-VASc scores. The best cut-off value of the AF-CA-Stroke score to predict future strokes was ≥ 5. Conclusions: This novel model-based point scoring system effectively identifies stroke risk using clinical factors and AF ablation status of patients with AF. Various age stratifications and AF ablation should be considered in AF management.

Background/Purpose: A deleterious effect of complete left bundle-branch block (cLBBB) on left ventricular (LV) function has been established. The underutilization of cardiac resynchronization therapy has been noted in Taiwan and the Asian-Pacific area, but the reasons remain unclear. This study aimed to evaluate the prevalence and association of cLBBB and impaired LV ejection fraction (LVEF) in patients at the National Taiwan University Hospital (NTUH). Methods: We enrolled 164,049 patients who underwent standard 12-lead electrocardiography (ECG) between January 2010 and December 2013 at NTUH. Echocardiographic examinations within one year of the index ECG were analyzed. Baseline clinical characteristics, electrocardiography and ECG parameters, in patients with cLBBB were compared among those with three different LVEFs (EF 80 years, 64% had a normal EF. However, in those aged between 40 and 60 years, the risk of EF

Background/purpose: Details of the communication between the caller and dispatcher have not been reported previously in Taiwan. This study aimed to: (1) understand the details of the communication between the caller and dispatcher among the calls for stroke patients, (2) identify factors associated with stroke recognition by dispatchers, and (3) evaluate the association between stroke recognition by dispatchers and stroke management. Methods: We conducted a retrospective observational study involving patients with stroke or transient ischemic stroke transported by the emergency medical service, and arriving at 9 hospitals in Taipei within 3 h of symptom onset from January 1, 2013 to February 28, 2014. Patients were excluded if tape-recording data or prehospital information were not available. Data of the enrolled patients were reviewed. We used stroke dispatch determination as the surrogate for stroke recognition by dispatchers. Multivariable logistic regression was used to identify the factors associated with stroke dispatch determination. Results: A total of 507 patients were included. In approximately 50% of cases, callers were close family members. Ninety-one patients (17.9%) had stroke dispatch determination. After adjustment, stroke reported spontaneously, any symptom included in the Cincinnati Prehospital Stroke Scale reported spontaneously, and dispatcher adherence to the protocol, were associated with stroke dispatch determination significantly. Stroke dispatch determination was associated with receiving pre-arrival notification, shorter door-to-computed tomography time, and thrombolytic therapy. Conclusion: The dispatchers should spend more time identifying stroke patients by following the dispatch protocol. Recognition of stroke by dispatchers was associated with improved stroke care. Keywords: Stroke, Dispatch, Thrombolytic therapy