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Background: This study aimed to evaluate the performance of a modified U.S. (MUS) model for risk prediction of cardiovascular (CV) events in Asian patients and compare it to European and Japanese models. Methods: The MUS model, based on the US ACC/AHA 2018 lipid treatment guideline, was employed to stratify patients under primary or secondary prevention. Two multi-center prospective observational registry cohorts, T-SPARCLE and T-PPARCLE, were used to validate the scoring system, and the primary outcome was the time to first occurrence/recurrence of major adverse cardiac events (MACEs). The MUS model's performance was compared to other models from Europe and Japan. Results: A total of 10,733 patients with the mean age of 64.2 (SD: 11.9) and 36.5% female were followed up for a median of 5.4 years. The MUS model was validated, with an AUC score of 0.73 (95% CI 0.68–0.78). The European and Japanese models had AUC scores ranging from 0.6 to 0.7. The MUS model categorized patients into four distinct CV risk groups, with hazard ratios (HRs) as follows: very high- vs. high-risk group (HR = 1.91, 95% CI 1.53–2.39), high- vs. moderate-risk group (HR = 2.08, 95% CI 1.60–2.69), and moderate- vs. low-risk group (HR = 3.14, 95% CI 1.63–6.03). After adjusting for the MUS model, a history of atherosclerotic vascular disease (ASCVD) was not a significant predictor of adverse cardiovascular outcomes within each risk group. Conclusion: The MUS model is an effective tool for risk stratification in Asian patients with and without ASCVD, accurately predicting MACEs and performing comparably or better than other established risk models. Our findings suggest that patient management should focus on background risk factors instead of solely on primary or secondary prevention.

Potent P2Y12 receptor antagonists have been used widely for patients undergoing percutaneous coronary intervention with different results. Benefits from different regimens various between trials. Randomized controlled trials (RCTs) have restrictive inclusion and exclusion criteria; thus, they may limit the generalizability of the findings to a broader population. This study was aimed to comprehensively investigate the outcomes of potent P2Y12 inhibitors in patients undergoing PCI, including RCTs and real-world evidence (RWE) studies.Multiple electronic databases were systemically reviewed and searched on compared potent P2Y12 inhibitors with clopidogrel. The primary efficacy end point was composite ischemic cardiovascular event and primary safety endpoint was major bleeding. Overall estimates of proportions and incidence rates with 95 % confidence intervals (CI) were calculated using fixed-effects models. Total 24 studies (140,986 patients) underwent coronary intervention were included in this meta-analysis, including 18 RCTs and 6 large cohort studies with propensity score matching. The potent P2Y12 inhibitors including cangrelor, prasugrel, and ticagrelor, significantly decreased the risk of composite adverse cardiovascular ischemic events (95 % CI 0.89–0.96, p

Abstract Background Renal function decline is a frequently encountered complication in patients with chronic coronary syndrome. Aside from traditional cardiovascular risk factors, the inflammatory burden emerged as the novel phenotype that compromised renal prognosis in such population. Methods A cohort with chronic coronary syndrome was enrolled to investigate the association between inflammatory status and renal dysfunction. Levels of inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), tumour necrosis factor-α (TNF-α), adiponectin, matrix metalloproteinase-9, interleukin-6, lipoprotein-associated phospholipase A2, were assessed. Renal event was defined as > 25% decline in estimated glomerular filtration rate (eGFR). Inflammatory scores were calculated based on the aggregate of hs-CRP, TNF-α, and adiponectin levels. Results Among the 850 enrolled subjects, 145 patients sustained a renal event during an averaged 3.5 years follow-up. Multivariate analysis with Cox regression suggested elevations in hs-CRP, TNF-α, and adiponectin levels were independent risk factors for the occurrence of a renal event. Whereas, Kaplan-Meier curve illustrated significant correlation between high TNF-α (P = 0.005), adiponectin (P

With the rapid development of information technology, digital health technologies have become increasingly prevalent in the field of healthcare. In this study, business intelligence (BI) techniques were combined with research-based prediction models to increase the efficiency and quality of healthcare practices. A data scenario involving 200 older adults with various measurements, including health beliefs, social support, self-efficacy, and disease duration, was used to establish a medication adherence prediction model in a BI system. A regression model, logistic regression model, tree model, and score-based prediction model were used to predict medication adherence among older adults. The developed BI-based prediction model has visualization, real-time feedback, and data updating functionality. These features enhanced the effectiveness of prediction models in clinical practice. Healthcare professionals can incorporate the proposed system into their care practice for health assessments and management, and patients can use the system to manage themselves. The developed BI-based care system can also be used to achieve effective communication and shared decision-making between care managers and patients. Further empirical studies integrating prediction models into the proposed BI system for assessment, management, and decision-making in healthcare practice are warranted.

Background: Osteopontin (OPN) is a noncollagenous matricellular protein which is mainly present in bone matrix. A high OPN level has been associated with heart failure and acute coronary syndrome, however data on patients with chronic coronary syndrome (CCS) are lacking. The present study aimed to evaluate the association between OPN and the prognosis of Taiwanese patients with CCS. Methods: We enrolled participants from the Biosignature Registry, a nationwide prospective cohort study conducted at nine different medical centers throughout Taiwan. The inclusion criteria were participants who had received successful percutaneous coronary intervention at least once previously, and stable under medical therapy for at least 1 month before enrollment. They were followed for at least 72 months. Logistic regression and Cox proportional hazard model were used to investigate the association between OPN and clinical outcomes. The outcomes of this study were the first occurrence of hard cardiovascular events and composite cardiovascular outcomes including cardiovascular mortality, revascularization, hospitalization for acute myocardial infarction (AMI) or heart failure. Results: A total of 666 patients with both hs-CRP and osteopontin measurements were enrolled and followed for 72 months. OPN was correlated positively with AMI-related hospitalization, where the highest tertile (Tertile 3) of baseline OPN had the highest risk of AMI-related hospitalization, which remained significant after multivariate adjustments (HR 3.20, p = 0.017). In contrast, combining OPN and hs-CRP did not improve the prediction of CV outcomes. Conclusion: OPN may be a potentially valuable biomarker in predicting CV outcomes. During 6 years of follow-up period, an OPN level >4810 pg/ml was associated with a significantly higher incidence of AMI-related hospitalization in CCS patients who received successful PCI before the enrollment.

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

Abstract Obesity is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). However, ‘obesity paradox’ is observed in patients with coronary artery disease while defining obesity by body mass index (BMI). The purpose of this study is to identify a better anthropometric parameter to predict cardiovascular events in patients with ASCVD. The study was conducted using the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. A total of 6,920 adult patients with stable ASCVD, enrolled from January 2010 to November 2014, were included, with a mean age of 65.9 years, 73.9% males, and a mean BMI of 26.3 kg/m2 at baseline. These patients were followed up for a median of 2.5 years. The study endpoint was the composite major adverse cardiovascular event (MACE), defined as cardiovascular death, nonfatal myocardial infarction or stroke, or cardiac arrest with resuscitation. Multivariable Cox proportional hazards regression showed a significant positive association between waist-to-BMI ratio and MACE (adjusted hazard ratio 1.69 per cm‧m2/kg increase in waist-to-BMI ratio, 95% CI 1.12–2.49, p = 0.01) after adjusting for potential risk factors and confounders. Traditional anthropometric parameters, such as BMI, weight, waist and waist-hip ratio, or newer waist-based indices, such as body roundness index and a body shape index, did not show any significant linear associations (p = 0.09, 0.30, 0.89, 0.54, 0.79 and 0.06, respectively). In the restricted cubic spline regression analysis, the positive dose–response association between waist-to-BMI ratio and MACE persisted across all the range of waist-to-BMI ratio. The positive dose–response association was non-linear with a much steeper increase in the risk of MACE for waist-to-BMI ratio > 3.6 cm‧m2/kg. In conclusion, waist-to-BMI ratio may function as a positive predictor for the risk of MACE in established ASCVD patients.

Coronary artery calcium (CAC) is a great risk predictor of the atherosclerotic cardiovascular disease and CAC scores can be used to stratify the risk of heart disease. Current clinical analysis of CAC is performed using onsite semiautomated software. This semiautomated CAC analysis requires experienced radiologists and radiologic technologists and is both demanding and time-consuming. The purpose of this study is to develop a fully automated CAC detection model that can quantify CAC scores. A total of 1,811 cases of cardiac examinations involving contrast-free multidetector computed tomography were retrospectively collected. We divided the database into the Training Data Set, Validation Data Set, Testing Data Set 1, and Testing Data Set 2. The Training, Validation, and Testing Data Set 1 contained cases with clinically detected CAC; Testing Data Set 2 contained those without detected calcium. The intraclass correlation coefficients between the overall standard and model-predicted scores were 1.00 for both the Training Data Set and Testing Data Set 1. In Testing Data Set 2, the model was able to detect clinically undetected cases of mild calcium. The results suggested that the proposed model’s automated detection of CAC was highly consistent with clinical semiautomated CAC analysis. The proposed model demonstrated potential for clinical applications that can improve the quality of CAC risk stratification.

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

ObjectivesThis study compared transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in terms of short- and long-term effectiveness.MethodsThis retrospective cohort study based on nationwide National Health Insurance claims data and Cause of Death data focused on adult patients (n = 3,643) who received SAVR (79%) or TAVR (21%) between 2015 and 2019. Propensity score overlap weighting was applied to account for selection bias. Primary outcomes included all-cause mortality (ACM), hospitalization for heart failure, and a composite endpoint of major adverse cardiac events (MACE). Secondary outcomes included medical utilization, hospital stay, and total medical costs at index admission for the procedure and in various post-procedure periods. The Cox proportional-hazard model with competing risk was used to investigate survival and incidental health outcomes. Generalized estimation equation (GEE) models were used to estimate differences in the utilization of medical resources and overall costs.ResultsAfter weighting, the mean age of the patients was 77.98 ± 5.86 years in the TAVR group and 77.98 ± 2.55 years in the SAVR group. More than half of the patients were female (53.94%). The incidence of negative outcomes was lower in the TAVR group than in the SAVR group, including 1-year ACM (11.39 vs. 17.98%) and 3-year ACM (15.77 vs. 23.85%). The risk of ACM was lower in the TAVR group (HR [95% CI]: 0.61 [0.44–0.84]; P = 0.002) as was the risk of CV death (HR [95% CI]: 0.47 [0.30–0.74]; P = 0.001) or MACE (HR [95% CI]: 0.66 [0.46–0.96]; P = 0.0274). Total medical costs were significantly higher in the TAVR group than in the SAVR in the first year after the procedure ($1,271.89 ± 4,048.36 vs. $887.20 ± 978.51; P = 0.0266); however, costs were similar in the second and third years after the procedure. The cumulative total medical costs after the procedure were significantly higher in the TAVR group than in the SAVR group (adjusted difference: $420.49 ± 176.48; P = 0.0172).ConclusionIn this real-world cohort of patients with aortic stenosis, TAVR proved superior to SAVR in terms of clinical outcomes and survival with comparable medical utilization after the procedure.

BackgroundProximal protection devices, such as the Mo.Ma system provides better neurological outcomes than the distal filter system in the carotid artery stenting (CAS) procedure. This study first evaluated the safety and efficacy of the Mo.Ma system during CAS in a single tertiary referral hospital from Taiwan. The outcomes of distal vs. proximal embolic protection devices were also studied.MethodsA total of 294 patients with carotid artery stenosis who underwent the CAS procedure were retrospectively included and divided into two groups: 152 patients in the distal filter system group and 142 patients in the Mo.Ma system. The outcomes of interest were compared between the two groups. The factors contributing to occlusion intolerance (OI) in the Mo.Ma system were evaluated.ResultsThe procedure success rates were more than 98% in both groups. No major stroke occurred in this study. The minor stroke rates were 2.8% (4/142) and 4.6% (7/152) in the Mo.Ma system and filter system, respectively (p = 0.419). Patients with hypoalbuminemia significantly predicted the risk of stroke with an odds ratio of 0.08 [95% confidence interval (CI), 0.01–0.68, p = 0.020] per 1 g/day of serum albumin in the filter group. A total of 12 patients developed OI in the Mo.Ma system (12/142, 8%). Low occlusion pressure predicted the occurrence of OI in the Mo.Ma group with the hazard ratios of 0.88 (95% CI: 0.82–0.96) and 0.90 (95% CI: 0.84–0.98) per 1 mmHg of occlusion systolic pressure (OSP) and diastolic pressure (ODP), respectively. We further indicated that patients with an OSP of ≥60 mmHg or an ODP of ≥44 mmHg could tolerate the procedure of occlusion time up to 400 s, while patients with an OSP of

BackgroundAlthough the COVID-19 pandemic has accelerated the adoption of telemedicine and virtual consultations worldwide, complex factors that may affect the use of virtual clinics are still unclear. ObjectiveThis study aims to identify factors associated with the utilization of virtual clinics in the experience of virtual clinic service implementation in Taiwan. MethodsWe retrospectively analyzed a total of 187,742 outpatient visits (176,815, 94.2%, in-person visits and 10,927, 5.8%, virtual visits) completed at a large general hospital in Taipei City from May 19 to July 31, 2021, after rapid implementation of virtual outpatient clinic visits due to the COVID-19 pandemic. Data of patients’ demographic characteristics, disease type, physicians’ features, and specialties/departments were collected, and physicians’ opinions regarding virtual clinics were surveyed and evaluated using a 5-point Likert scale. Multilevel analysis was conducted to determine the factors associated with the utilization of virtual clinics. ResultsPatient-/visit-, physician-, and department-level factors accounted for 67.5%, 11.1%, and 21.4% of the total variance in the utilization of virtual clinics, respectively. Female sex (odds ratio [OR] 1.27, 95% CI 1.22-1.33, P50 km, P

Background: Fatty-acid binding protein-4 (FABP4) has been associated with the metabolic syndrome, diabetes mellitus, atherosclerosis, incident heart failure, and the prognosis of coronary heart disease (CHD). However, recent studies have not reported a significant correlation between FABP4 and cardiovascular (CV) mortality in high-risk patients or those with documented CHD. The present study aimed to evaluate the association between FABP4 and the prognosis in a cohort of patients with CHD who received coronary interventions. Methods: Serum FABP4 levels were measured in 973 patients after a successful intervention for CHD, who were then prospectively followed for 30 months. Result: During this period, 223 patients experienced composite CV outcomes (22.92%), defined as cardiovascular/cerebrovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for refractory or unstable angina, hospitalization for heart failure, and peripheral artery occlusive disease. Kaplan–Meier curves showed a significant association between FABP4 levels at baseline (categorized in tertiles) and composite CV outcomes during follow-up (log-rank test, p

Abstract Endothelial progenitor cells (EPCs) improve endothelial impairment, which in turn restores endothelial function in patients with heart failure (HF). In the present study, we tested whether fenofibrate, with its anti-inflammatory and vasoprotective effects, could improve myocardial function by activating EPCs through the eNOS pathway in a doxorubicin (DOX)-induced cardiomyopathy mouse model. Wild-type mice were divided into 4 groups and treated with vehicle, DOX + saline, DOX + fenofibrate, and DOX + fenofibrate + L-NAME (N(ω)-nitro-L-arginine methyl ester). DOX-induced cardiac atrophy, myocardial dysfunction, the number of circulating EPCs and tissue inflammation were analyzed. Mice in the DOX + fenofibrate group had more circulating EPCs than those in the DOX + saline group (2% versus 0.5% of total events, respectively) after 4 weeks of treatment with fenofibrate. In addition, the inhibition of eNOS by L-NAME in vivo further abolished the fenofibrate-induced suppression of DOX-induced cardiotoxic effects. Protein assays revealed that, after DOX treatment, the differential expression of MMP-2 (matrix metalloproteinase-2), MMP-9 (matrix metalloproteinase-9), TNF-α (tumor necrosis factor-α), and NT-pro-BNP (N-terminal pro-B-type natriuretic peptide) between saline- and DOX-treated mice was involved in the progression of HF. Mechanistically, fenofibrate promotes Akt/eNOS and VEGF (vascular endothelial growth factor), which results in the activation of EPC pathways, thereby ameliorating DOX-induced cardiac toxicity.

ObjectiveCurrent guidelines recommend that transcatheter aortic valve replacement (TAVR) for bicuspid aortic valve (BAV) with aortic stenosis (AS) should only be performed in selected patients. However, we consider it even more crucial to identify what the really important factors are while determining long-term outcomes in patients with BAV undergoing TAVR, which is precisely the aim of this study.MethodsWe retrospectively evaluated consecutive patients who underwent TAVR with balloon-expandable Sapien XT or Sapien 3 valves (Edwards Lifesciences, Irvine, CA) for the treatment of severe bicuspid AS. The primary end points were major adverse cardiac and cerebral events (MACCE), that is, mortality, non-fatal myocardial infarction (MI), disabling stroke, valve failure needing reintervention, or clinically relevant valve thrombosis during follow-up.ResultsA total of 56 patients who underwent TAVR with Sapien XT (n = 20) or Sapien 3 (n = 36) were included. The device and procedural success rates were similar between the two TAVR valves; however, the newer-generation Sapien 3 yielded a trend toward better long-term clinical outcomes than the early-generation Sapien XT did (MACCE rates 35 vs. 11%, p = 0.071). In the multivariate Cox proportional hazards analyses, the presence of calcified raphe > 4 mm was the only independent predictor of long-term MACCE (hazard ratio: 6.76; 95% confidence interval: 1.21–37.67, p = 0.029).ConclusionTAVR performed by a skilled heart team, while using newer-generation balloon-expandable Sapien 3 valve, may yield better long-term clinical outcomes compared to TAVR using early-generation Sapien XT valve. Moreover, the presence of calcified raphe >4 mm is an independent determinant of adverse clinical outcomes.

Abstract In patients with atherosclerotic cardiovascular disease (ASCVD) under statin treatment, the influence of on-treatment level of high-density lipoprotein cholesterol (HDL-C) on cardiovascular (CV) events is controversial. Statin-treated patients were selected from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry, a multicenter, observational study of adult patients with ASCVD in Taiwan. Low HDL-C was defined as

Abstract Aims We collected the different prescription patterns of diabetes medications in a cohort of patients with heart failure with reduced ejection fraction (HFrEF) and analysed the impact of different prescription patterns on clinical outcomes. Methods and results Consecutive diabetic patients with HFrEF from a heart failure referral centre were retrospectively analysed between 2015 and 2016. Exclusion criteria include being lost to follow‐up, not receiving diabetes medications, and having severe renal impairment with a glomerular filtration rate < 30 mL/min/1.73 m2. Prescription of diabetes medications and the respective clinical outcomes were collected between 2016 and 2018. Among 381 patients (mean age, 64.8 ± 12.8 years; 71.9% male; mean left ventricular ejection fraction, 27.6 ± 7.0%; mean body mass index, 26.1 ± 4.7 kg/m2), the prescription rates of sodium‐glucose co‐transporter 2 inhibitor (SGLT2i) increased from 10.3% in 2016 to 17.6% in 2017 and 26.5% in 2018 (P < 0.001); the prescription rates of metformin, sulfonylurea, insulin, and dipeptidyl peptidase‐4 inhibitors did not change significantly over time. The prescription rates of metformin and SGLT2i were significantly higher in patients managed by cardiologists than non‐cardiologists (in 2018, 71.1% vs. 44.2% for metformin, 45.4% vs. 9.9% for SGLT2i, both P < 0.001). During the study period, annualized event rates of cardiovascular death or first unplanned HF hospitalization were 19.0 per 100 patient‐years. After a multivariate analysis, prescriptions of metformin {odds ratio (OR): 0.49 [95% confidence interval (CI) 0.27–0.51], P < 0.001} and SGLT2i [OR: 0.52 (95% CI 0.28–0.98), P = 0.042] were independently associated with lower annualized event rates of cardiovascular death or unplanned HF hospitalization. Conclusions Prescription patterns of diabetes medications in diabetics with HFrEF were diverse among different specialists. Prescriptions of metformin and SGLT2i were associated with favourable clinical outcomes. Our finding indicates the importance of awareness of beneficial effect of different classes of diabetes medications and collaboration between specialists in the management of diabetic HFrEF patients.

Background: Few studies have characterized electrocardiography (ECG) patterns correlated with left ventricular (LV) systolic dysfunction in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS).Objectives: This study aims to develop ECG pattern-derived scores to predict LV systolic dysfunction in NSTE-ACS patients.Methods: A total of 466 patients with NSTE-ACS were retrospectively enrolled. LV ejection fraction (LVEF) was assessed by echocardiography within 72 h after the first triage ECG acquisition; there was no coronary intervention in between. ECG score was developed to predict LVEF < 40%. Performance of LVEF, the Global Registry of Acute Coronary Events (GRACE), Thrombolysis in Myocardial Infarction (TIMI) and ECG scores to predict 24-month all-cause mortality were analyzed. Subgroups with varying LVEF, GRACE and TIMI scores were stratified by ECG score to identify patients at high risk of mortality.Results: LVEF < 40% was present in 20% of patients. We developed the PQRST score by multivariate logistic regression, including poor R wave progression, QRS duration > 110 ms, heart rate > 100 beats per min, and ST-segment depression ≥ 1 mm in ≥ 2 contiguous leads, ranging from 0 to 6.5. The score had an area under the curve (AUC) of 0.824 in the derivation cohort and 0.899 in the validation cohort for discriminating LVEF < 40%. A PQRST score ≥ 3 could stratify high-risk patients with LVEF ≥ 40%, GRACE score > 140, or TIMI score ≥ 3 regarding 24-month all-cause mortality.Conclusions: The PQRST score could predict LVEF < 40% in NSTE-ACS patients and identify patients at high risk of mortality in the subgroups of patients with LVEF ≥ 40%, GRACE score > 140 or TIMI score ≥ 3.

Background: Some personality types are associated with cardiovascular (CV) diseases and may be related to clinical outcomes in coronary artery disease (CAD). This study investigates the association between type D personality and clinical outcomes in stable CAD patients in an Asian cohort. Methods: Stable CAD patients were enrolled and prospectively followed up for at least 1 year in Taiwan. The inclusion criteria were at least one successful percutaneous coronary intervention (PCI) and stable medical treatment for at least 1 month before enrollment. Vulnerability to psychological distress was measured by the Type D Personality Scale (DS14) after enrollment. The end point was the occurrence of total CV events. Cox regression models of CV events were used to investigate the role of type D personality in clinical outcomes. Results: The study included 777 patients, among which 122 (15.77%) had type D personality. Forty-two CV events were identified: 3 cardiac deaths, 5 nonfatal myocardial infarctions, 1 stroke, 4 congestive heart failures (CHF), 6 peripheral arterial occlusive disorder cases, and 23 readmissions for angina/revascularization treatment. Patients with type D personality had significantly higher incidence of future CV events (9.84% vs. 4.58%, p = 0.018%) and admission for angina/revascularization (5.74% vs. 2.44%, p = 0.049). Patients with subsequent CV events were more likely to have type D personality (28.57% vs. 14.97%, p=0.018). After proportional Cox regression analysis, type D personality remained an independent predictor of future CV events (HR: 3.21, 95% CI: 1.06–9.69). In subgroup analyses, type D personality was especially associated with higher risk of total CV events among females, the elderly, hypertension patients, diabetes patients, and non-smokers. Conclusion: Type D personality was an independent predictor of CV outcomes in an Asian cohort of stable CAD patients. This personality type may be identified in risk stratification for secondary prevention after PCI. Keywords: Type D personality, Coronary artery disease

Purpose: In this study, transapical transcatheter mitral valve-in-valve implantation (TAMVI) was compared with surgical redo mitral valve replacement (SRMVR) in terms of clinical outcomes.Methods: We retrospectively identified patients with degenerated mitral bioprosthesis or failed annuloplasty rings who underwent redo SRMVR or TAMVI at our medical center. Clinical outcomes were based on echocardiography results.Results: We retrospectively identified patients with symptomatic mitral bioprosthetic valve dysfunction (n = 58) and failed annuloplasty rings (n = 14) who underwent redo SRMVR (n = 36) or TAMVI (n = 36). The Society of Thoracic Surgeons Predicted Risk of Mortality scores were higher in the TAMVI group (median: 9.52) than in the SRMVR group (median: 5.59) (p-value = 0.02). TAMVI patients were more severe in New York Heart Association (p-value = 0.04). The total procedure time (skin to skin) and length of stay after procedures were significantly shorter in the TAMVI group, and no significant difference in mortality was noted after adjustment for confounding factors (p-value = 0.11). The overall mean mitral valve pressure gradient was lower in the TAMVI group than in the SRMVR group at 24 months (p < 0.01). Both groups presented a decrease in the severity of mitral and tricuspid regurgitation at 3–24 months.Conclusions: In conclusion, the statistical analysis is still not robust enough to make a claim that TAMVI is an appropriate alternative. The outcome of the patient appears only to be related to the patient's pre-operative STS score. Additional multi-center, longitudinal studies are warranted to adequately assess the effect of TAMVI.

Objectives Transcatheter aortic valve replacement (TAVR) is increasingly performed. Physically small Asians have smaller aortic root and peripheral vessel anatomy. The influence of gender of Asian patients undergoing TAVR is unknown and may affect outcomes. The aim of this study was to assess sex differences in Asian patients undergoing TAVR.Methods Patients undergoing TAVR from eight countries were enrolled. In this retrospective analysis, we examined differences in characteristics, 30-day clinical outcomes and 1-year survival between female and male Asian patients.Results Eight hundred and seventy-three patients (54.4% women) were included. Women were older, smaller and had less coronary artery and lung disease but tended to have higher logistic EuroSCOREs. Smaller prostheses were used more often in women. Major vascular complications occurred more frequently in women (5.5% vs 1.8%, p

Introduction Optimal antithrombotic strategy following transcatheter aortic valve replacement (TAVR) is still unknown. We hypothesised that the direct factor Xa inhibitor edoxaban can potentially prevent subclinical leaflet thrombosis and cerebral embolisation compared with conventional dual antiplatelet therapy (DAPT) in patients undergoing TAVR.Methods and analysis The ADAPT-TAVR trial is an international, multicentre, randomised, open-label, superiority trial comparing edoxaban-based strategy and DAPT strategy in patients without an indication for oral anticoagulation who underwent successful TAVR. A total of 220 patients are randomised (1:1 ratio), 1–7 days after successful TAVR, to receive either edoxaban (60 mg daily or 30 mg daily if patients had dose-reduction criteria) or DAPT using aspirin (100 mg daily) plus clopidogrel (75 mg daily) for 6 months. The primary endpoint was an incidence of leaflet thrombosis on four-dimensional, volume-rendered cardiac CT imaging at 6 months post-TAVR. The key secondary endpoints were the number of new lesions and new lesion volume on brain diffusion-weighted MRI and the changes in neurological and neurocognitive function assessment between immediate post-TAVR and 6 months of study drug administration. Detailed clinical information on thromboembolic and bleeding events were also assessed.Ethics and dissemination Ethic approval has been obtained from the Ethics Committee/Institutional Review Board of Asan Medical Center (approval number: 2017–1317) and this trial is also approved by National Institute of Food and Drug Safety Evaluation of Republic of Korea (approval number: 31511). Results of this study will be disseminated in scientific publication in reputed journals.Trial registration number NCT03284827.

Background: The aim of this study is to determine the relationship between the on-treatment lipid profiles and the CV events in CKD and non-CKD population. Method: This study was a multi-center observational registry, the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. This study follows up patients with CV diseases in Taiwan who have secondary prevention therapies. The primary outcome is the time of first occurrence of a major adverse cardiac events (MACEs). Result: 5388 patients with ASCVD were included and 1478 (27.4%) had CKD without dialysis. CKD patients had higher TG and lower LDL-C levels. The incidence of recurrent MACEs per 1000 person-years in CKD patients was 19.5 (95% CI 15.5–24.9), compared with 9.1 (95% CI 7.4–11.1) in non-CKD patients. In patients with statin therapy, there were no differences in MACE risk between each level of on-treatment LDL-C, TG and HDL-C level. Higher on-treatment non-HDL-C level was a significant predictor for higher MACE risk in patients without CKD, and borderline significant in CKD patients under statin therapy. Heart failure history was also associated with higher MACE risk in both group. Lower body mass index (BMI

Abstract A prospective observational study was conducted to investigate the residual risk factors to predict recurrence of major adverse cardiovascular events (MACE) in atherosclerotic cardiovascular disease (ASCVD) patients with a high prevalence under lipid-lowering therapy, particularly in the subpopulations of diabetic and nondiabetic individuals. A total of 5,483 adults (with a mean age of 66.4 and 73.3% male) with established coronary heart disease, cerebrovascular disease, or peripheral artery disease were identified from the T-SPARCLE multi-center registry. Of them, 38.6% had diabetes. The residual risk factors for MACE are divergent in these atherosclerotic patients with and without diabetes. In diabetic subpopulation, the risk of MACE was significantly increased with heart failure (HF), chronic kidney disease (CKD) stage 4–5 (vs. stage 1–2), without beta blocker use, and higher non-HDL-C, after controlling for covariates including statin use and the intensity of therapy. Increased LDL-C and TG levels were also associated with increased risk, but to a much less extent. Among nondiabetic individuals, HF, CKD stage 4–5, and history of myocardial infarction were the significant independent predictors of MACE. It is suggested that ASCVD patients with concomitant diabetes need stricter control of lipid, particularly non-HDL-C levels, to reduce cardiovascular risk when on statin therapy.

Abstract Background The volume and percentage of percutaneous coronary interventions (PCIs) performed for nonacute indications have declined in the United States since 2007. However, little is known if similar trends occurred in Taiwan. Methods We used data from Taiwan National Health Insurance inpatient claims to examine the regional and hospital variations in the extent of decline in the percentage of nonacute indication PCIs from 2007 to 2012. Results The volume of total PCIs persistently increased from 29,032 in 2007 to 35,811 in 2010 and 37,426 in 2012. However, the volume of nonacute indication PCIs first increased from 7916 in 2007 to 9143 in 2009 and then decreased to 8666 in 2012. The percentage of nonacute indication PCIs steadily decreased from 27% in 2007 to 26% in 2009 and then to 23% in 2012, a − 15% change. The extent of decline was largest in the North region (from 27% to 21 %, a − 22% change) and least in Kaopin region (from 20% to 18%, a − 13% change). Of the 71 hospitals studied, 14 did not show a decreasing trend. Five of the 14 hospitals even showed an increasing trend, with a percentage change >10% between 2007 and 2012. In 2012, 6 hospitals had a nonacute indication PCI percentage >35%. Conclusions In Taiwan, four-fifths of the hospitals showed a decline in the percentage of nonacute indication PCIs from 2007 to 2012. It is plausible that Taiwanese cardiologists would have been influenced by the recommendations of crucial US trials and guidelines.

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

Atrial fibrillation (AF) is the most common sustained arrhythmia. Both the incidence and prevalence of AF are increasing, and the burden of AF is becoming huge. Many innovative advances have emerged in the past decade for the diagnosis and management of AF, including a new scoring system for the prediction of stroke and bleeding events, the introduction of non-vitamin K antagonist oral anticoagulants and their special benefits in Asians, new rhythm- and rate-control concepts, optimal endpoints of rate control, upstream therapy, life-style modification to prevent AF recurrence, and new ablation techniques. The Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology aimed to update the information and have appointed a jointed writing committee for new AF guidelines. The writing committee members comprehensively reviewed and summarized the literature, and completed the 2016 Guidelines of the Taiwan Heart Rhythm Society and the Taiwan Society of Cardiology for the Management of Atrial Fibrillation. This guideline presents the details of the updated recommendations, along with their background and rationale, focusing on data unique for Asians. The guidelines are not mandatory, and members of the writing committee fully realize that treatment of AF should be individualized. The physician's decision remains most important in AF management.

Aggressive and persistent control of risk factors is recommended for prevention of secondary comorbidities in patients with cardiovascular diseases. This study aimed to evaluate guideline recommendations for achieving targets for lipid and blood pressure (BP) control in patients with cardiovascular diseases in Taiwan. Methods: This multicenter cohort study was conducted in 14 hospitals in Taiwan. A total of 3316 outpatients who had established cerebrovascular disease (CVD), coronary artery disease (CAD), or both were recruited. Risk factors for comorbid conditions such as high BP, sugar, hemoglobin A1C, abnormal lipids, lipoproteins, and medication use were compared between patients with CVD, CAD, or both. Results: Of all patients, 503 (15.2%) had CVD only, 2568 (77.4%) had CAD only, and 245 (7.4%) had both CVD and CAD. Compared with patients who had only CAD, those with CVD were older, had higher frequency of hypertension, and lower frequency of diabetes mellitus. Patients with CAD were more likely to receive lipid-lowering and antihypertensive drugs than those with CVD (p

Whether a low-density lipoprotein cholesterol (LDL-C) goal is essential in secondary prevention is still being debated. The aim of our study was to investigate whether achieving particular LDL-C level goals is associated with the reduction in the risk of major adverse cardiac events (MACEs) in patients with atherosclerotic cardiovascular diseases (ASCVD) on statin therapy.From January 2010 to August 2014, a total of 4099 patients with ASCVD in the Taiwan Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) registry were analyzed. The risk of a MACE was lower in patients with LDL-C level under control at < 100 mg/dL by statins than in patients with LDL-C level ≥100 mg/dL whether on statin therapy (hazard ratio [HR] 1.66, 95% confidence interval [CI] 1.04‒2.63, p = 0.03) or not (HR 2.04, 95% CI 1.06‒3.94, p = 0.03). In multivariate Cox model analyses, statin intensity had no significant predictive value, and LDL-C ≥ 100 mg/dL was associated with a slight but not significant trend toward increased risk of MACEs (HR 1.41, 95% CI 0.96‒2.07, p = 0.08).For patients with ASCVD on statin therapy guided by a target-driven strategy, failure to control LDL-C levels to < 100 mg/dL was associated with higher risk of MACEs. Statin intensity alone had no significant impact on the risk of MACEs after multivariate adjustment.

Peroxisome proliferator-activated receptor α (PPARα) plays a role in the pathogenesis of cardiac hypertrophy, although its underlying mechanism remains unclear. The purpose of this study was to evaluate the effect of PPARα activation on endothelin-1- (ET-1-) caused cardiomyocyte hypertrophy and explore its underlying mechanisms. Human cardiomyocytes (HCMs) were cultured with or without ET-1, whereafter the inhibitory effects of fenofibrate, a PPARα activator, on cell size and adiponectin protein were tested. We examined the activation of extracellular signal-regulated kinase (ERK) and p38 proteins caused by ET-1 and the inhibition of the ERK and p38 pathways on ET-1-induced cell size and adiponectin expression. Moreover, we investigated the interaction of PPARα with adiponectin and nuclear factor-κB (NF-κB) by electrophoretic mobility shift assays and coimmunoprecipitation. ET-1 treatment significantly increased cell size, suppressed PPARα expression, and enhanced the expression of adiponectin. Pretreatment with fenofibrate inhibited the increase in cell size and enhancement of adiponectin expression. ET-1 significantly activated the ERK and p38 pathways, whereas PD98059 and SB205380, respectively, inhibited them. Our results suggest that activated PPARα can decrease activation of adiponectin and NF-κB and inhibit ET-1-induced cardiomyocyte hypertrophy.

Background: Dyslipidemia is an important but modifiable risk factor of cardiovascular disease (CVD). However, no nationwide registry has been designed so far to document the inter-relationship between long-term clinical outcomes and the lipid control, and the use of lipid-lowering agents for secondary prevention of cardiovascular events in patients with established CVD in a large representative sample of public and private hospitals in Taiwan. Methods: In this registry-type prospective observational study, we sought to record information with regard to the secondary prevention of patients with stable symptomatic atherosclerotic disease, classified by the presence of one of the following conditions: evidence of coronary artery disease, cerebrovascular disease, or peripheral vascular disease, focusing on lipid management, and long-term outcomes. The data on customary Taiwanese clinical practice applied to outpatients will be collected from 14 centers across Taiwan, including public and private hospitals, and will be clinically followed for 5 years after their inclusion. Results: The analysis of this multicenter registry will demonstrate the treatment patterns, goal attainment, factors influencing treatment, and the clinical outcomes among patients suffering from CVD in Taiwan. Conclusions: The registry may increase our understanding of the prevalence and consequences of atherothrombosis on a nationwide basis. In addition to academic interests, the results may have impact on future clinical practice pattern and national policy on lipid management in Taiwan.

Background Studies in the United States suggested that the characteristics of hospitals providing percutaneous coronary intervention (PCI) differed from those not providing PCI. However, little is known on the differences between the characteristics of early‐adopting hospitals and those of late‐adopting hospitals, and on their potential impacts on PCI volume and access. Methods and Results We used inpatient claims data from 1997 to 2012 from the Taiwan National Health Insurance program to identify the hospitals offering PCI. Geographic information systems (GIS) were used to determine the population access to PCI hospital. As of 2012, 88 hospitals were capable of providing PCI. On the basis of the year that the hospitals started providing PCI, 32 hospitals were designated as early adopters (before 1998), 23 as early majority (1998–2002), 24 as late majority (2003–2007), and 16 as laggards (2008–2012). Hospitals that adopted PCI later were smaller in size and closer to an existing PCI hospital and had lower PCI volumes performed and less bypass surgery support. The median PCI volumes in 2012 were n=706, 330, 138, and 81 in early adopters, early majority, late majority, and laggards, respectively. Despite the low volume of PCI performed in laggard hospitals, the percentage with ST‐elevation myocardial infarction and acute myocardial infarction as principal discharge diagnosis was higher than their early‐adopting hospital counterparts. The percentage of the Taiwanese population living within 40 km of PCI hospitals (appropriate access defined in this study) was 95.7% in 1997 and 98.0% in 2002, and this has remained unchanged since 2002. Conclusions The characteristics of early‐adopting hospitals differed from those of late‐adopting hospitals. Despite lower PCI volume performed in late‐adopting hospitals, many of them are in remote areas and provide needed and timely services for patients with acute myocardial infarction.

Epidemiological and clinical studies have clearly established the link between low-density lipoprotein cholesterol (LDL-C) and atherosclerosis-related cardiovascular consequences. Although it has been a common practice for physicians to prescribe lipid-lowering therapy for patients with dyslipidemia, the achievement rate is still not satisfied in Taiwan. Therefore, the determinants for achieving the LDL-C target needed to be clarified for better healthcare of the patients with dyslipidemia.This registry-type prospective observational study enrolled the patients with cardiovascular diseases (coronary artery disease (CAD) and cerebrovascular disease (CVD)) from 18 medical centers across Taiwan, and clinically followed them for five years. At every clinical visit, vital signs, clinical endpoints, adverse events, concurrent medications and laboratory specimens were obtained as thoroughly as possible. The lipid profile (total cholesterol, high-density lipoprotein cholesterol, LDL-C, triglyceride), liver enzymes, and creatinine phosphokinase were evaluated at baseline, and every year thereafter. The cross sectional observational data was analyzed for this report.Among the 3,486 registered patients, 54% had their LDL-C < 100 mg/dL. By univariate analysis, the patients achieving the LDL-C target were associated with older age, more male sex, taller height, lower blood pressure, more under lipid-lowering therapy, more smoking cessation, more history of CAD, DM, physical activity, but less history of CVD. The multivariate analysis showed statin therapy was the most significant independent determinant for achieving the treatment target, followed by age, history of CAD, diabetes, blood pressure, and sex. However, most patients were on regimens of very-low to low equipotent doses of statins.Although the lipid treatment guideline adherence is improving in recent years, only 54% of the patients with cardiovascular diseases have achieved their LDL-C target in Taiwan, and the most significant determinant for this was statin therapy.

BACKGROUND: Pulse pressure (PP) is a risk factor for cardiovascular disease. It has been reported that ambulatory blood pressure (BP) and nighttime BP parameters are heritable traits. However, the genetic association of pulse pressure and its clinical impact remain undetermined. METHOD AND RESULTS: We conducted a genome-wide association study of PP using ambulatory BP monitoring in young-onset hypertensive patients and found a significant association between nighttime PP and SNP rs897876 (p = 0.009) at chromosome 2p14, which contains the predicted gene FLJ16124. Young-onset hypertension patients carrying TT genotypes at rs897876 had higher nighttime PP than those with CT and CC genotypes (TT, 41.6 ± 7.3 mm Hg; CT, 39.1 ± 6.0 mm Hg; CC, 38.9 ± 6.3 mm Hg; p

Heat-shock proteins (HSPs) are molecular chaperones that protect proteins from damage. HSP27 expression is associated with cancer transformation and invasion. Ginkgo biloba extract (EGb761), the most widely sold herbal supplement, has antiangiogenic effects and induces tumor apoptosis. Data regarding the effect of EGb761 on HSP expression is limited, particularly in cancer. HSP27 expression in paired tumors and normal lung tissues of 64 patients with non-small cell lung cancer (NSCLC) were detected by real-time PCR, western blotting, and immunohistochemistry. NSCLC cell lines (A549/H441) were used to examine the migratory abilities in vitro. NSCLC tissue showed higher HSP27 expression than normal lung tissue. Kaplan-Meier survival analysis showed that NSCLC patients with low HSP27 expression ratio (1) (p = 0.04). EGb761 inhibited HSP27 expression and migratory ability of A549/H441 cells, which is the same as HSP27-siRNA transfection effect. Moreover, EGb761 treatment activated the AKT and p38 pathways and did not affect the expression of PI3K, ERK, and JNK pathways. HSP27 is a poor prognostic indicator of NSCLC. EGb761 can decrease the migration ability of A549/H441 by inhibiting HSP27 expression most likely through AKT and p38 MAPK pathways activation.

Hypertension is a complex disorder with high prevalence rates all over the world. We conducted the first genome-wide gene-based association scan for hypertension in a Han Chinese population. By analyzing genome-wide single-nucleotide-polymorphism data of 400 matched pairs of young-onset hypertensive patients and normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100 susceptibility genes for hypertension were identified and also validated with permutation tests. Seventeen of the 100 genes exhibited differential allelic and expression distributions between patient and control groups. These genes provided a good molecular signature for classifying hypertensive patients and normotensive controls. Among the 17 genes, IGF1, SLC4A4, WWOX, and SFMBT1 were not only identified by our gene-based association scan and gene expression analysis but were also replicated by a gene-based association analysis of the Hong Kong Hypertension Study. Moreover, cis-acting expression quantitative trait loci associated with the differentially expressed genes were found and linked to hypertension. IGF1, which encodes insulin-like growth factor 1, is associated with cardiovascular disorders, metabolic syndrome, decreased body weight/size, and changes of insulin levels in mice. SLC4A4, which encodes the electrogenic sodium bicarbonate cotransporter 1, is associated with decreased body weight/size and abnormal ion homeostasis in mice. WWOX, which encodes the WW domain-containing protein, is related to hypoglycemia and hyperphosphatemia. SFMBT1, which encodes the scm-like with four MBT domains protein 1, is a novel hypertension gene. GRB14, TMEM56 and KIAA1797 exhibited highly significant differential allelic and expressed distributions between hypertensive patients and normotensive controls. GRB14 was also found relevant to blood pressure in a previous genetic association study in East Asian populations. TMEM56 and KIAA1797 may be specific to Taiwanese populations, because they were not validated by the two replication studies. Identification of these genes enriches the collection of hypertension susceptibility genes, thereby shedding light on the etiology of hypertension in Han Chinese populations.

Young-onset hypertension has a stronger genetic component than late-onset counterpart; thus, the identification of genes related to its susceptibility is a critical issue for the prevention and management of this disease. We carried out a two-stage association scan to map young-onset hypertension susceptibility genes. The first-stage analysis, a genome-wide association study, analyzed 175 matched case-control pairs; the second-stage analysis, a confirmatory association study, verified the results at the first stage based on a total of 1,008 patients and 1,008 controls. Single-locus association tests, multilocus association tests and pair-wise gene-gene interaction tests were performed to identify young-onset hypertension susceptibility genes. After considering stringent adjustments of multiple testing, gene annotation and single-nucleotide polymorphism (SNP) quality, four SNPs from two SNP triplets with strong association signals (-log(10)(p)>7) and 13 SNPs from 8 interactive SNP pairs with strong interactive signals (-log(10)(p)>8) were carefully re-examined. The confirmatory study verified the association for a SNP quartet 219 kb and 495 kb downstream of LOC344371 (a hypothetical gene) and RASGRP3 on chromosome 2p22.3, respectively. The latter has been implicated in the abnormal vascular responsiveness to endothelin-1 and angiotensin II in diabetic-hypertensive rats. Intrinsic synergy involving IMPG1 on chromosome 6q14.2-q15 was also verified. IMPG1 encodes interphotoreceptor matrix proteoglycan 1 which has cation binding capacity. The genes are novel hypertension targets identified in this first genome-wide hypertension association study of the Han Chinese population.