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Background: The VICTORIA trial demonstrated a significant decrease in cardiovascular events through vericiguat therapy. This study aimed to assess the potential mechanisms responsible for the reduction of cardiovascular events with vericiguat therapy in a rabbit model of myocardial infarction (MI)., Methods: A chronic MI rabbit model was created through coronary artery ligation. Following 4 weeks, the hearts were harvested and Langendorff perfused. Subsequently, electrophysiological examinations and dual voltage-calcium optical mapping studies were conducted at baseline and after administration of vericiguat at a dose of 5 μmol/L., Results: Acute vericiguat therapy demonstrated a significant reduction in premature ventricular beat burden and effectively suppressed ventricular arrhythmic inducibility. The electrophysiological influences of vericiguat therapy included an increased ventricular effective refractory period, prolonged action potential duration, and accelerated intracellular calcium (Cai) homeostasis, leading to the suppression of action potential and Cai alternans. The pacing-induced ventricular arrhythmias exhibited a reentrant pattern, attributed to fixed or functional conduction block in the peri-infarct zone. Vericiguat therapy effectively mitigated the formation of cardiac alternans as well as the development of reentrant impulses, providing additional anti-arrhythmic benefits., Conclusions: In the MI rabbit model, vericiguat therapy demonstrates anti-ventricular arrhythmia effects. The vericiguat therapy reduces ventricular ectopic beats, inhibiting the initiation of ventricular arrhythmias. Furthermore, the therapy successfully suppresses cardiac alternans, preventing conduction block and, consequently, the formation of reentry circuits., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The echocardiographic parameter E/e' has been associated with cardiovascular (CV) events. However, few studies have analyzed multiple associated CV outcomes using E/e' in a diverse population of both inpatients and outpatients with and without cardiac diseases and risk factors., Methods: Medical records of 75,393 patients without atrial fibrillation (AF) with first available E/e' were retrieved from our hospital database. Patients with mitral valve disease were excluded, and the remainder were studied in protocol 1 (70,819 patients). Patients with hypertension, diabetes mellitus, hyperlipidemia, CV diseases, prior CV events, CV surgeries, and left ventricular ejection fraction <50% or missing left ventricular ejection fraction were further excluded, and the remaining patients were studied in protocol 2 (14,665 patients). The study outcomes are major adverse CV events (MACE), which included myocardial infarction (MI), AF, ischemic and hemorrhagic stroke (IHS), hospitalization for heart failure (HHF), and cardiac death. The primary outcomes were MACE and each of the MACE components., Results: At the end of maximal 5-year follow-up (median 22.18 months with interquartile range 7.20-49.08 months for MACE in protocol 1 and 23.46 months with interquartile range 8.15-49.02 months for MACE in protocol 2), compared with an E/e' value of <8, an intermediate value of E/e' 8 to 15 and a high value of E/e' >15 were significantly associated with MACE, MI, AF, IHS, HHF, and cardiac death in protocol 1 (all P < .0001). In protocol 2, an intermediate E/e' value of 8 to 15 and a high value of E/e' >15 were significantly associated with MACE, MI, AF, IHS, HHF, and CV death (all P < .05), except an intermediate value E/e' 8 to 15 was not associated with AF., Conclusions: In a diverse population of inpatients and outpatients with and without cardiac diseases and risk factors, the echocardiographic parameter E/e' was associated with CV events and is a useful marker of risk., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Coronary artery disease is the most common cause of heart failure (HF) in developed countries. The aim of this study was to elucidate the mechanisms of reduction of arrhythmias after sacubitril/valsartan (LCZ696) therapy in a myocardial infarction (MI)-HF rabbit model., Methods and Results: Chronic MI in rabbits with HF were divided into 3 groups: placebo control, valsartan 30 mg/day and LCZ696 60 mg/day. After 4 weeks of therapy, an electrophysiologic study and a dual voltage-calcium optical mapping study were performed. The LCZ696 group had significantly better left ventricular ejection fraction and lower ventricular tachyarrhythmia inducibility than the valsartan and placebo groups. The most common ventricular tachyarrhythmia pattern was 1 or 2 ectopic beats originating from the peri-infarct areas, followed by re-entrant beats surrounding phase singularity points. Compared to the valsartan and placebo groups, the LCZ696 group had significantly shorter action-potential duration, shorter intracellular calcium tau constant, faster conduction velocity, and shorter pacing cycle length to induce arrhythmogenic alternans. LCZ696 therapy reduced the phosphorylated calmodulin-dependent protein kinase II (CaMKII-p) expression., Conclusions: In a rabbit model with chronic MI and HF, LCZ696 therapy ameliorated postinfarct heart function impairment and electrophysiologic remodeling and altered CaMKII-p expression, leading to reduced ventricular tachyarrhythmia inducibility., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims/introduction: The cardiovascular (CV) outcomes of vildagliptin - a dipeptidyl peptidase-4 inhibitor - in patients with type 2 diabetes mellitus after acute coronary syndrome or acute ischemic stroke are unclear., Materials and Methods: We analyzed data from the Taiwan National Health Insurance Research Database on 3,750 type 2 diabetes mellitus patients with acute coronary syndrome or acute ischemic stroke within 3 months between 1 August 2011 and 31 December 2013. Clinical outcomes were evaluated by comparing 1,250 participants receiving vildagliptin with 2,500 propensity score-matched participants. The primary composite outcome included CV death, non-fatal myocardial infarction and non-fatal stroke., Results: The primary composite outcome occurred in 122 patients (9.8%) in the vildagliptin group and 263 patients (10.5%) in the control group (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.72-1.11) with a mean follow-up period of 9.9 months. No significant between-group differences were observed for CV death (HR 0.93, 95% CI 0.56-1.52), non-fatal myocardial infarction (HR 0.79, 95% CI 0.46-1.36) and non-fatal stroke (HR 0.96, 95% CI 0.74-1.24). The vildagliptin group was at similar risks of hospitalization for heart failure (HF) or coronary intervention to the control group (P = 0.312 and 0.430, respectively). For patients with HF at baseline, the risk of hospitalization for HF was similar between the vildagliptin and control groups (HR 1.04, 95% CI 0.57-1.88)., Conclusions: Among patients with type 2 diabetes mellitus after a recent acute coronary syndrome or acute ischemic stroke, treatment with vildagliptin was not associated with increased risks of CV death, non-fatal myocardial infarction, non-fatal stroke and hospitalization for HF., (© 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: This study investigated the predictors of subsequent cardiovascular events in stable post-myocardial infarction patients in Taiwan., Methods: A total of 11,183 patients were recruited who had survived one year post-myocardial infarction without subsequent events of recurrent myocardial infarction or stroke from the Taiwan National Health Insurance Research Database. Their composite cardiovascular event rates were identified., Results: The composite cardiovascular events rate in three year follow-up in the post-myocardial infarction population was 13.8%. Corresponding event rates were 5.8% recurrent myocardial infarction, 5.0% stroke, and 5.2% death. Independent factors associated with a higher risk of ischemic events or death included heart failure (hazard ratio (HR)=1.19), hypertension (HR=1.16), age (65-75 vs <65 years: HR=1.29; 75-85 vs <65 years: HR=1.50; >85 vs <65 years: HR=1.70), diabetes (HR=1.33), prior stroke (HR=1.24), chronic kidney disease (HR=1.4), atrial fibrillation (HR=1.27), and underutilization of guideline-based medication (HR=1.73). Composite risk for myocardial infarction, stroke and death increased progressively from 4.9% in patients with zero risk factor to 100.0% in patients with eight risk factors., Conclusions: For acute myocardial infarction patients surviving one year without subsequent events of recurrent myocardial infarction or stroke, the risk of cardiovascular events remained high. Eight predictors identified patients at increased risk for subsequent cardiovascular events within the next three years. These results suggest an unmet need, particularly in patients with additional risk factors.

Background: LCZ696 (valsartan/sacubitril) therapy significantly reduced mortality in patients with heart failure (HF). Although a clinical trial (PARADISE-MI Trial) has been ongoing to examine the effects of LCZ696 in myocardial infarction (MI) patients, the effects of LCZ696 on remodeling of cardiac electrophysiology in animal models remain largely unclear., Methods: We performed coronary artery ligation to create MI in Sprague-Dawley rats. Echocardiography was performed one week after MI to confirm the development of HF with left ventricular ejection fraction ≤ 40%. MI rats were randomly assigned to receive medical therapy for 4 weeks: LCZ696, enalapril, or vehicle. The sham-operation rats received sham operation without MI creation. In vivo electrophysiological exams were performed under general anesthesia. Western blot analyses were conducted to quantify ion channel proteins., Results: The HF-vehicle group did not show significant changes in LVEF. Both enalapril and LCZ696 therapy significantly improved LVEF. The HF-vehicle group had higher ventricular arrhythmia (VA) inducibility than the sham group. As compared with the HF-vehicle group, LCZ696 therapy significantly reduced VA inducibility, but enalapril therapy did not. Western blot analyses showed significant downregulation of Na V 1.5, ERG, KCNE1, and KCNE2 channel proteins in the HF vehicle group compared with the sham group. LCZ696 therapy upregulated protein expression of ERG, KCNE1, and KCNE2., Conclusion: As compared with enalapril therapy, LCZ696 therapy led to improvement of LVEF, reduced VA inducibility, and upregulated expression of K + channel proteins., Competing Interests: The authors have no conflicts of interest., (Copyright © 2019 Po-Cheng Chang et al.)

Objective: Whether the cardiovascular (CV) outcomes of second-generation limus-eluting stents (LESs) differ from those of paclitaxel-eluting stents (PESs) in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) is still unclear., Methods: We used the Taiwan National Health Insurance Research Database to analyse data of 516 patients with AMI and CS diagnosed from January 2007 to December 2011. We used propensity score matching to adjust for the imbalance in covariate baseline values between these two groups. We evaluated clinical outcomes by comparing 197 subjects who used second-generation LESs to 319 matched subjects who used PESs., Results: The risk of the primary composite outcomes (i.e., myocardial infarction, coronary revascularisation or CV death) was significantly lower in the second-generation LES group than in the PES group [37.3% vs. 51.8%; hazard ratio (HR), 0.73; 95% CI: 0.56-0.95] at the 12-month follow-up. The patients who received second-generation LESs had a lower risk of coronary revascularisation (HR 0.62; 95% CI: 0.41-0.93) than those who used PESs. However, the risks of myocardial infarction (HR 0.56; 95% CI: 0.26-1.24), ischemic stroke (HR 0.73; 95% CI: 0.23-2.35), or CV death (HR 0.90; 95% CI: 0.63-1.28) were not significantly different between the two groups., Conclusions: Among patients with CS-complicating AMI, second-generation LES implantation significantly reduced the risk of coronary revascularisation and composite CV events compared to PES implantation at the 12-month follow-up., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Hypertrophic cardiomyopathy (HCM) entails thickening of the myocardium and an increased risk of ischaemia. However, the prognosis of patients with HCM with acute myocardial infarction (AMI) is incompletely understood., Methods: Medical information was retrieved from the Taiwan National Health Insurance Research Database in 1997-2011. The exclusion criteria were patients <18 years old, and history of AMI, coronary intervention, aortic valve disease, disease of the pericardium, heart surgery, device implantation, venous thromboembolism, cardiac transplant, congenital heart disease and end-stage renal disease on dialysis. Patients with HCM with AMI were compared with propensity score (PS)-matched patients with AMI without HCM. The primary endpoints were in-hospital and 1-year cardiovascular events., Results: In total, 201 166 patients were admitted for AMI. There were 177 058 patients with new-onset AMI, 257 with HCM and 176 801 without HCM after exclusion criteria. Using 1:4 PS matching, the study population consisted of patients with AMI, 257 with HCM and 1028 without HCM. Patients with AMI with HCM received significantly less coronary intervention (OR=0.46; 95% CI 0.32 to 0.65; p<0.001), coronary intervention with stenting (OR=0.33; 95% CI 0.20 to 0.57; p<0.001) and coronary artery bypass graft surgery (OR=0.22; 95% CI 0.05 to 0.90; p=0.036), and fewer episodes of shock (OR=0.64; 95% CI 0.48 to 0.86; p=0.003) and in-hospital death (OR=0.46; 95% CI 0.30 to 0.70; p<0.001), compared with patients with AMI without HCM. Specifically, for patients with HCM with AMI, AMI occurred predominantly (82.5%) in the form of ischaemia without requiring coronary stenting. Patients with AMI with HCM had significantly better survival than patients without HCM (HR=0.66; 95% CI 0.51 to 0.85; p=0.001) during the 1-year follow-up., Conclusions: This is the first PS-matched study to compare the prognosis of patients with AMI with and without HCM. Compared with patients with AMI without HCM, patients with HCM had significantly better in-hospital and within 1-year outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Irisin, a recently identified myokine, regulates mitochondrial function and energy expenditure. The concentration of irisin is significantly altered after ST-elevation myocardial infarction (STEMI). We hypothesized that serum irisin concentration is associated with adverse cardiovascular outcomes after myocardial infarction. Serum irisin concentrations were measured using enzyme-linked immunosorbent assay (ELISA) in 399 patients 28d after the onset of STEMI in a prospective single-center cohort study. We assessed the association between irisin concentrations and adverse cardiovascular events during a 3-year follow-up. The excess risks of cardiovascular mortality, stroke, heart failure, and revascularization were predominantly seen among those with the highest concentrations of irisin, with concentrations higher than 75th percentile of the overall distribution had a ~4-fold increase in risk (hazard ratio=3.96, 95% confidence interval 1.55 to 10.11, P<0.01). Our findings showed that serum concentrations of irisin are elevated in post-STEMI patients with increased risk for adverse cardiovascular events. Novel therapies targeting irisin may represent a new direction in the treatment of STEMI., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Purpose Our aim was to determine whether cardiovascular (CV) risk in patients with prostate cancer (PCa) differs between those who receive androgen-deprivation therapy by surgical castration and those who receive gonadotropin-releasing hormone agonist (GnRHa) therapy. Patients and Methods By using the Taiwan National Health Insurance Research Database, we analyzed data from 14,715 patients with PCa diagnosed from January 1, 1997, through December 31, 2011. The patients were treated with bilateral orchiectomy or GnRHa therapy. We used inverse probability of treatment weighting with propensity scores to adjust for the imbalance in covariate baseline values between these two groups. Cox regression models were used to identify risk factors for myocardial infarction (MI), ischemic stroke (IS), and cardiac-related complications. Results Overall, 3,578 patients with PCa (24.3%) underwent bilateral orchiectomy and 11,137 patients (75.7%) received GnRHa therapy. Both groups had a similar risk of CV ischemic events (ie, MI or IS; hazard ratio, 1.16; 95% CI, 0.97 to 1.38) during a median follow-up time of 3.3 years. However, during the first 1.5 years of follow-up, there were higher CV ischemic events in the orchiectomy group than in the GnRHa group (hazard ratio, 1.40; 95% CI, 1.04 to 1.88), particularly in patients who were ≥ 65 years of age, had hypertension, had a Charlson comorbidity index score ≥ 3, and had a previous history of MI, IS, or coronary heart disease. Conclusion Compared with bilateral orchiectomy, use of GnRHa does not increase the risk of CV ischemic events in patients with PCa. Nonetheless, orchiectomy is associated with higher rates of CV ischemic events in older patients and those with a history of CV comorbidities within 1.5 years of initiating androgen-deprivation therapy. These findings can help clinicians decide on the optimal castration strategy for individual patients.

Importance: The heritability of atrial fibrillation (AF), the contribution of genetic and environmental factors, and the association of a family history of AF with prognosis are unclear., Objectives: To measure genetic and environmental factors in the familial aggregation of AF and to estimate the association of a family history of AF with major adverse cardiovascular events (MACE)., Design, Setting, and Participants: In this Taiwanese nationwide population-based study among more than 23 million people, a custom data set was obtained using the data of all patients having a diagnosis of AF recorded between January 1996 and December 2013 in the Taiwan National Health Insurance Research Database. The study population comprised all 23 422 955 individuals registered with the database in 2013, of whom 177 770 had a diagnosis of AF and were included in the heritability estimation. From the latter, a subgroup of patients having newly diagnosed AF with a first-degree relative affected by AF between 2000 and 2010 were selected and matched 1:4 to controls without a family history for estimating MACE-free survival. The dates of analysis were January 2010 to December 2013., Main Outcomes and Measures: The prevalence and relative risk of AF in relatives of patients with AF, as well as the relative contributions of heritability and shared and nonshared environmental factors to AF susceptibility. Also measured was MACE-free survival after AF was diagnosed., Results: In total, 1510 patients (204 [13.5%] female; mean [SD] age, 57.9 [9.2] years) had newly diagnosed AF with a first-degree relative affected by AF. Individuals with a first-degree relative affected by AF had a relative risk of 1.92 (95% CI, 1.84-1.99) for AF. The accountability for the phenotypic variance of AF was 19.9% for genetic factors (heritability), 3.5% for shared environmental factors, and 76.6% for nonshared environmental factors. After matching for age, sex, hypertension, type 2 diabetes, previous stroke, and anticoagulation, incident AF patients with vs without an affected first-degree relative had similar MACE-free survival., Conclusions and Relevance: Genetic and environmental factors were associated with AF, with nonshared environmental factors accounting for three-fourths of the phenotypic variance in Taiwan. Patients having AF with a first-degree relative affected by AF did not have more MACE. Therefore, family history may not be particularly informative in the diagnosis or management of AF.

Background: Prior studies have suggested intraaortic balloon pump (IABP) have a neutral effect on acute myocardial infarction (AMI) patients with cardiogenic shock (CS). However, the effects of IABP on patients with severe CS remain unclear. We therefore investigated the benefits of IABP in AMI patients with severe CS undergoing coronary revascularization., Methods and Results: This study identified 14,088 adult patients with AMI and severe CS undergoing coronary revascularization from Taiwan's National Health Insurance Research Database between January 1, 1997 and December 31, 2011, dividing them into the IABP group (n = 7044) and the Nonusers group (n = 7044) after propensity score matching to equalize confounding variables. The primary outcomes included myocardial infarction(MI), cerebrovascular accidents or cardiovascular death. In-hospital events including dialysis, stroke, pneumonia and sepsis were secondary outcomes. Primary outcomes were worse in the IABP group than in the Nonusers group in 1 month (Hazard ratio (HR) = 1.97, 95% confidence interval (CI) = 1.84-2.12). The MI rate was higher in the IABP group (HR = 1.44, 95% CI = 1.16-1.79), and the cardiovascular death was much higher in the IABP group (HR = 2.07, 95% CI = 1.92-2.23). The IABP users had lower incidence of dialysis (8.5% and 9.5%, P = 0.04), stroke (2.6% and 3.8%, P<0.001), pneumonia (13.9% and 16.5%, P<0.001) and sepsis (13.2% and 16%, P<0.001) during hospitalization than Nonusers., Conclusion: The use of IABP in patients with myocardial infarction and severe cardiogenic shock undergoing coronary revascularization did not improve the outcomes of recurrent myocardial infarction and cardiovascular death. However, it did reduce the incidence of dialysis, stroke, pneumonia and sepsis during hospitalization.

Background: To investigate the cardiovascular (CV) outcomes of drug-eluting stents (DESs) versus bare-metal stents (BMSs) in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS)., Methods: Data from the Taiwan National Health Insurance Research Database was analyzed between January 1, 2007 and December 31, 2011. A total of 3051 AMI patients in CS were selected as the study cohort. Their clinical outcomes were evaluated by comparing 1017 subjects who used DESs to 2034 matched subjects who used BMSs., Results: The risk of the primary composite outcome (i.e., death, myocardial infarction, stroke, and coronary revascularization) was significantly lower in the DES group compared with the BMS group [56.1% vs. 66.2%, hazard ratio (HR), 0.74; 95% CI, 0.67-0.81] with a mean follow-up of 1.35years. The patients who received DESs had a lower risk of coronary revascularization (HR, 0.78; 95% CI, 0.67-0.91) and death (HR, 0.70; 95% CI, 0.62-0.79) than those who used BMSs. However, the risks of myocardial infarction (HR, 0.89; 95% CI, 0.66-1.18), ischemic stroke (HR, 1.02; 95% CI, 0.67-1.53) and major bleeding (HR, 0.80; 95% CI, 0.56-1.14) were similar between the two groups., Conclusions: Among patients with CS complicating AMI, DES implantation significantly reduced the risk of percutaneous coronary revascularization and death compared to BMS implantation., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Data on the cardiovascular (CV) outcomes of drug-eluting stents (DES) vs. bare-metal stents (BMS) in patients with acute myocardial infarction (AMI) under dialysis are limited., Methods and results: We analyzed the data from 42,592 AMI patients in the Taiwan National Health Insurance Research Database between 1 January 2007 and 31 December 2011. A total of 984 AMI patients under dialysis were selected as the study cohort. We evaluated the clinical outcomes by comparing 492 subjects who had DES to 492 matched subjects who had BMS. The primary composite outcomes, which included recurrent MI, coronary revascularization and CV death, were significantly lower in the DES group than in the BMS group (41.7% vs. 47.6%, hazard ratio (HR), 0.77; 95% confidence interval (CI), 0.63-0.92, P=0.005) after mean 1.2 years. The patients who received DES had a lower risk of recurrent MI (HR, 0.63; 95% CI, 0.45-0.90), CV death (HR, 0.74; 95% CI, 0.56-0.98) and all-cause mortality (HR, 0.74; 95% CI, 0.61-0.89) than those who used BMS, but a similar risk of major bleeding (HR, 0.99; 95% CI, 0.69-1.42, P=0.952) and ischemic stroke (HR, 1.15; 95% CI, 0.66-2.01, P=0.631)., Conclusions: Among AMI patients on dialysis undergoing percutaneous coronary interventions, DES implantation significantly reduced the risk of recurrent MI, CV death and all-cause mortality compared with BMS implantation.

Background: Na(+)/Ca(2+) exchanger blockade has been reported to be anti-arrhythmic in different models. The effects of KB-R7943, a Na(+)/Ca(2+) exchanger blocker, on arrhythmogenesis in hearts with chronic myocardial infarction (MI) remain unclear., Methods: Dual voltage and intracellular Ca(2+) (Cai) optical mapping was performed in nine rabbit hearts with chronic MI and four control hearts. Electrophysiology studies including inducibility of ventricular tachyarrhythmias, ventricular fibrillation dominant frequency, action potential, Cai alternans, Cai decay, and conduction velocity were performed. The same protocol was repeated in the presence of KB-R7943 (0.5, 1, and 5μM) after the baseline studies., Results: KB-R7943 was effective in suppressing afterdepolarizations and spontaneous ventricular tachyarrhythmias in hearts with chronic MI. Surprisingly, KB-R7943 increased the inducibility of ventricular tachyarrhythmias in a dose-dependent manner (11%, 11%, 22%, and 56% at baseline and with 0.5, 1, and 5μM KB-R7943, respectively, p=0.02). Optical mapping analysis revealed that the underlying mechanisms of the induced ventricular tachyarrhythmias were probably spatially discordant alternans with wave breaks and rotors. Further analysis showed that KB-R7943 significantly enhanced both action potential (p=0.033) and Cai (p=0.001) alternans, prolonged Cai decay (tau value) in a dose-dependent manner (p=0.004), and caused heterogeneous conduction delay especially at peri-infarct zones during rapid burst pacing. In contrast, KB-R7943 had insignificant effects in control hearts., Conclusions: In this chronic MI rabbit model, KB-R7943 has contrasting effects on arrhythmogenesis, suppressing afterdepolarizations and spontaneous ventricular tachyarrhythmias, but enhancing the inducibility of tachyarrhythmias. The mechanism is probably the enhanced spatially discordant alternans because of prolonged Cai decay and heterogeneous conduction delay., (Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: The cardiovascular safety and efficacy of sitagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, in type 2 diabetic patients after acute myocardial infarction (AMI) has so far remained uncertain., Methods: We analyzed data from the National Health Insurance Research Database (NHIRD), a government-operated, population-based database, from March 1st, 2009 to December 31st, 2011. Type 2 diabetic patients hospitalized for AMI were included in our study. We compared subjects using sitagliptin with comparison group to evaluate its cardiovascular safety and efficacy. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and ischemic stroke., Results: We identified a total of 3,282 type 2 diabetic patients hospitalized for AMI (mean follow-up 1.15 years). Of these patients, 547 (16.7%) who were exposed to sitagliptin were defined as the sitagliptin group and 2,735 (83.3 %) who did not use sitagliptin were the comparison group. The incidence of primary composite cardiovascular outcomes was 9.50 per 100 person-years in the sitagliptin group and was 9.70 per 100 person-years in the comparison group (hazard ratio (HR), 0.97; 95% CI, 0.73-1.29, P=0.849). Compared to the non-sitagliptin group, the sitagliptin group had similar risks of all-cause mortality, hospitalization for heart failure (HF) or percutaneous coronary intervention (PCI) with a HR of 0.82 (95% CI, 0.61-1.11, P=0.195), 0.93 (95% CI, 0.67-1.29, P=0.660), and 0.93 (95% CI, 0.75-1.14, P=0.473), respectively., Conclusion: The use of sitagliptin in type 2 diabetic patients with recent AMI was not associated with increased risk of adverse cardiovascular events.

Background: The cardiovascular safety and efficacy of sitagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, in type 2 diabetic patients with chronic kidney disease (CKD) after acute myocardial infarction (AMI) are unclear., Methods: We analyzed data from the Taiwan National Health Insurance Research Database between March 1st, 2009 and December 31st, 2011. A total of 1025 AMI patients with diabetes with chronic kidney disease were selected as the study cohort. The study evaluated the cardiovascular safety and efficacy of sitagliptin by comparing 205 subjects (20%) who use sitagliptin to 820 matched subjects (80%) who do not. The primary outcomes included myocardial infarction, ischemic stroke or cardiovascular death., Results: Primary composite outcomes occurred in 54 patients in the sitagliptin group (26.3%) and in 164 patients in the comparison group (20.0%) (HR, 1.32; 95% CI, 0.97-1.79; P=0.079) during the mean follow-up of 1.02years (SD=0.71years). The sitagliptin group had similar risks of ischemic stroke, all-cause mortality or hospitalization for heart failure (HF) compared to the non-sitagliptin group (P=0.938, 0.523 and 0.795 respectively). However, sitagliptin use was associated with increased risks of recurrent myocardial infarction (HR, 1.73; 95% CI, 1.15-2.58; P=0.008) and percutaneous coronary revascularization (HR, 1.43; 95% CI, 1.04-1.95; P=0.026)., Conclusions: Among type 2 diabetic patients with CKD after AMI, the use of sitagliptin was not associated with an increased risk of cardiovascular death, ischemic stroke or hospitalization for HF but was associated with increased risks of recurrent MI and percutaneous coronary revascularization., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background/purpose: Evidence-based guidelines have been formulated for optimal management of acute coronary syndrome (ACS). The Taiwan ACS Full Spectrum Registry aimed to evaluate the ACS management and identify the predictors of clinical outcomes of death/myocardial infarction/stroke 1 year post hospital discharge., Methods: Three thousand and eighty confirmed ACS patients enrolled in this registry were followed up for 1 year at 3-month intervals. Patient data on medical interventions as well as clinical events were recorded and analyzed by descriptive statistics., Results: One-year mortality among patients with ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and unstable angina was 6.1%, 10.1%, and 6.2%, respectively. Use of secondary preventive therapies was suboptimal throughout the follow-up phase, especially dual antiplatelet therapy, which fell from 74.8% patients at discharge to 24.9% patients at 1-year follow-up. The odds of an adverse incidence of death/myocardial infarction/stroke 1 year after discharge was significantly reduced in patients receiving aspirin and clopidogrel for ≥9 months and was consequently higher in patients in whom dual antiplatelet therapy was discontinued or prescribed for <9 months. Chronic renal failure, in-hospital bleeding, a diagnosis of NSTEMI, and antiplatelet therapy discontinuation had a negative association with 1-year outcomes, whereas the use of drug-eluting stents and antiplatelet agents, clopidogrel and aspirin, were predictors of positive outcomes., Conclusion: There is a significant deviation from evidence-based guidelines in ACS management in Taiwan as reported in other countries. Policy adherence, especially with regard to dual antiplatelet therapy may hold the key to long-term favorable outcomes and improved survival rates in ACS patients in Taiwan., (Copyright © 2013. Published by Elsevier B.V.)

Background: The stability of dynamic factors has been reported to play a role in the antiarrhythmic actions of adenosine triphosphate (ATP)-sensitive potassium channel (KATP) opener in phase-2 myocardial infarction (MI) hearts. In the situation of the downregulation of KATP, the effects of KATP blocker (HMR1098) on the dynamic factors and electrophysiological changes during phase-2 MI remain unclear., Methods: Dual voltage and intracellular Ca(2+) (Cai) optical mapping was performed in nine Langendorff-perfused hearts 4-5 hours after coronary artery ligation and five control hearts. Electrophysiology studies, including action potential duration (APD) restitution, conduction velocity (CV), inducibility of ventricular fibrillation (VF), VF dominant frequency, APD and Cai alternans, and Cai decay, were performed. The same protocol was repeated in the presence of HMR1098 (10 μm) after the baseline studies., Results: HMR1098 significantly prolonged APD and effective refractory period to prevent sustained VF in five of nine MI hearts and two of five control hearts compared to none at baseline in both groups. On the other hand, HMR1098 steepened APD restitution slope to enhance spatially concordant alternans in both groups. In the phase-2 MI group, HMR1098 steepened CV restitution slope and enhanced spatially discordant alternans (SDA), which might account for a decreased pacing threshold of VF induction during HMR1098 infusion in phase-2 MI hearts., Conclusions: In phase-2 MI hearts, HMR1098 has contrasting effects on arrhythmogenesis, suppressing reentry and VF persistence but facilitating VF inducibility. The mechanism is the intensified induction of SDA because of the steepened APD and CV restitution slopes., (©2014 Wiley Periodicals, Inc.)

Introduction: Dantrolene prevents arrhythmogenic Ca(2+) release during heart failure (HF). However, direct evidence to support its antiarrhythmic effects in failing hearts with acute myocardial infarction (AMI) is lacking., Methods and Results: HF was induced by right ventricular pacing (312 beats/min, 4 weeks) in 19 rabbits. AMI was induced by coronary artery ligation in rabbits surviving chronic pacing (n = 17). The hearts were quickly excised and Langendorff-perfused for simultaneous membrane potential and intracellular Ca(2+) (Cai ) optical mapping when ventricular fibrillation (VF) occurred or 4 hours after AMI. The VF inducibility was defined as the ability to provoke sustained VF (>2 minutes) by pacing. Dantrolene (10 μM) was administered after baseline studies. Spontaneous VF occurred in 5 rabbits (SVF group). The ventricular premature beat (VPB) burden was significantly higher in the SVF group than the non-SVF group (P < 0.05). Dantrolene suppressed VPB burden (P = 0.03) and prolonged action potential duration (APD; P < 0.05) to reduce VF inducibility (P < 0.05). However, dantrolene shortened immediate postshock APD50 even if VF storm was suppressed., Conclusion: In failing hearts with AMI, VPB burden plays a pivotal role in SVF occurrence. Dantrolene suppresses VPBs and/or prolongs repolarization to inhibit spontaneous VF and reduce VF inducibility., (© 2013 Wiley Periodicals, Inc.)

Background: The effects of SEA0400, a Na(+) /Ca(2+) exchanger (NCX) blocker, on dynamic factors and arrhythmogenic alternans in 1-month myocardial infarction (MI) hearts remain unknown., Methods: Simultaneous voltage and intracellular Ca(2+) (Cai ) optical mapping was performed in 12 rabbit hearts with MI for 1 month and six normal rabbit hearts as control. Western-blot studies were performed in both groups in an additional six hearts for each. Action potential duration (APD) restitution was constructed and arrhythmogenic alternans was induced by dynamic pacing. SEA0400 (0.03, 3 μM) was administered after baseline studies., Results: SEA0400 suppressed pacing-induced ventricular premature beats in a concentration-dependent manner. SEA0400 at 0.03 μM steepened APD restitution slopes and enhanced spatially discordant alternans (SDA), which became insignificant at 3 μM. The VF inducibility was seven of nine at baseline, nine of nine at 0.03 μM SEA0400, and five of nine at 3 μM SEA0400 (P = NS). Significant upregulation of NCX in the remote but not periinfarct zone and less degree downregulation of DHP1α in the remote versus periinfarct zone may play a role in enhancing SDA induction by SEA0400 in 1-month MI hearts., Conclusions: In 1-month MI hearts, SEA0400 suppresses pacing-induced ventricular premature beats, but also is proarrhythmic by steepening APD restitution and enhancing SDA via NCX inhibition. Heterogeneous upregulation of NCX and downregulation of DHP1α may contribute to SDA augmentation by SEA0400 in this model. The insignificant effect of SEA0400 on VF inducibility suggests that suppression of both reentry and triggered activity is required to suppress VF induction in this model., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

Background: Nicorandil (a K(ATP) opener) administration is reported to reduce ventricular arrhythmias 4.8 ± 2.2 hours after myocardial infarction (MI). The electrophysiological changes and the effects on dynamic factors and dynamically induced spatially discordant alternans by nicorandil during phase-2 MI are unclear., Methods: Simultaneous voltage and intracellular Ca(2+) (Ca(i)) optical mapping was performed in nine Langendorff-perfused hearts 4-5 hours after coronary artery ligation and nine control hearts. Action potential duration (APD) restitution was constructed and arrhythmogenic alternans was induced by dynamic pacing. Western blot studies (Kir6.1 and Kir6.2) were performed in six more hearts for both groups. Nicorandil (100 μM) was administered after baseline studies., Results: Phase-2 MI hearts showed longer APD, slower conduction velocity (CV), and higher ventricular fibrillation (VF) inducibility than the control hearts. Nicorandil shortened and restored APD without significant arrhythmogenic effects, and also increased the rate of Ca(i) reuptake and flattened CV restitution to suppress spatially discordant alternans, which might account for a tendency toward higher VF threshold with nicorandil infusion in phase-2 MI hearts. Immunoblotting studies showed significant down-regulation of K(ATP) protein expression, which was functionally correlated to the blunted APD shortening response to nicorandil., Conclusions: K(ATP) expression is down-regulated in phase-2 MI hearts. Nicorandil restores APD, increases the rate of Ca(i) reuptake, and flattens CV restitution to suppress spatially discordant alternans induction, which ameliorates its proarrhythmic effects during phase-2 MI., (©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.)

We hypothesize that remodelling of action potential and intracellular calcium (Ca(i)) dynamics in the peri-infarct zone contributes to ventricular arrhythmogenesis in the postmyocardial infarction setting. To test this hypothesis, we performed simultaneous optical mapping of Ca(i) and membrane potential (V(m)) in the left ventricle in 15 rabbit hearts with myocardial infarction for 1 week. Ventricular premature beats frequently originated from the peri-infarct zone, and 37% showed elevation of Ca(i) prior to V(m) depolarization, suggesting reverse excitation-contraction coupling as their aetiology. During electrically induced ventricular fibrillation, the highest dominant frequency was in the peri-infarct zone in 61 of 70 episodes. The site of highest dominant frequency had steeper action potential duration restitution and was more susceptible to pacing-induced Ca(i) alternans than sites remote from infarct. Wavebreaks during ventricular fibrillation tended to occur at sites of persistently elevated Ca(i). Infusion of propranolol flattened action potential duration restitution, reduced wavebreaks and converted ventricular fibrillation to ventricular tachycardia. We conclude that in the subacute phase of myocardial infarction, the peri-infarct zone exhibits regions with steep action potential duration restitution slope and unstable Ca(i) dynamics. These changes may promote ventricular extrasystoles and increase the incidence of wavebreaks during ventricular fibrillation. Whereas increased tissue heterogeneity after subacute myocardial infarction creates a highly arrhythmogenic substrate, dynamic action potential and Ca(i) cycling remodelling also contribute to the initiation and maintenance of ventricular fibrillation in this setting.

Acute myocardial infarction (AMI) can be caused by a ruptured plaque with sudden thrombosis occlusion or an embolization formation. Previous investigations have described the use of thrombolytic therapy, balloon angioplasty plus stenting, and various mechanical thrombectomy devices to treat patients with AMI with intracoronary thrombus, but all of these methods have certain limitations. The authors report 2 cases of AMI, 1 caused by ruptured plaque and the other caused by embolization, with large thrombus formation and total occlusion of the infarct-related artery. Manual thrombosuction with the Export catheter proved effective and safe for treating these 2 patients and achieved final thrombolysis in myocardial infarction (TIMI) III flow with good myocardial brushing.

Background: Patients with multivessel disease (MVD) often pursue complete revascularization (CR) during percutaneous coronary intervention (PCI) to improve prognosis. However, angiographic CR is not always feasible and is associated with some procedure-related complications in heart failure (HF) patients with MVD. Clinical selective incomplete revascularization (IR) may be reasonable for these high-risk patients, but its role in long-term outcomes remains uncertain.Methods: Six hundred patients with HF and MVD submitted to PCI were enrolled. Major adverse cardiac events (MACEs) were defined as a composite of recurrent myocardial infarction, any revascularization, and all-cause mortality at 5 years.Results: During a mean follow-up period of 3.7 ± 1.9 years, there was no significant difference in 5-year MACEs between selective IR and successful angiographic CR in HF patients with MVD. However, patients who failed CR had a significantly greater incidence of 5-year MACEs than those in the other two groups (failed CR: 46.4% vs. selective IR: 27.7% vs. successful CR: 27.8%, p < 0.001).Conclusions: Long-term outcomes of selective IR were comparable with those of successful angiographic CR in HF patients with MVD. However, patients that failed CR showed 2.53-fold increased risk of MACEs compared to patients undergoing either selective IR or successful angiographic CR. A more comprehensive planning strategy should be devised before PCI in HF patients with MVD. [ABSTRACT FROM AUTHOR]

Seismocardiogram (SCG) or mechanocardiography is a noninvasive cardiac diagnostic method; however, previous studies used only a single sensor to detect cardiac mechanical activities that will not be able to identify location-specific feature points in a cardiac cycle corresponding to the four valvular auscultation locations. In this study, a multichannel SCG spectrum measurement system was proposed and examined for cardiac activity monitoring to overcome problems like, position dependency, time delay, and signal attenuation, occurring in traditional single-channel SCG systems. ECG and multichannel SCG signals were simultaneously recorded in 25 healthy subjects. Cardiac echocardiography was conducted at the same time. SCG traces were analyzed and compared with echocardiographic images for feature point identification. Fifteen feature points were identified in the corresponding SCG traces. Among them, six feature points, including left ventricular lateral wall contraction peak velocity, septal wall contraction peak velocity, transaortic peak flow, transpulmonary peak flow, transmitral ventricular relaxation flow, and transmitral atrial contraction flow were identified. These new feature points were not observed in previous studies because the single-channel SCG could not detect the location-specific signals from other locations due to time delay and signal attenuation. As the results, the multichannel SCG spectrum measurement system can record the corresponding cardiac mechanical activities with location-specific SCG signals and six new feature points were identified with the system. This new modality may help clinical diagnoses of valvular heart diseases and heart failure in the future. [ABSTRACT FROM PUBLISHER]

Introduction: Carotid artery stenosis is one of the leading causes of ischemic stroke. Carotid artery stenting has become well-established as an effective treatment option for carotid artery stenosis. For this study, we aimed to determine the efficacy and safety of carotid stenting in a population-based large cohort of patients by analyzing the Taiwan National Healthcare Insurance (NHI) database. Methods: 2,849 patients who received carotid artery stents in the NHI database from 2004 to 2010 were identified. We analyzed the risk factors of outcomes including major adverse cardiovascular events including death, acute myocardial infarction, and cerebral vascular accidents at 30 days, 1 year, and overall period and further evaluated cause of death after carotid artery stenting. Results: The periprocedural stroke rate was 2.7% and the recurrent stroke rate for the overall follow-up period was 20.3%. Male, diabetes mellitus, and heart failure were significant risk factors for overall recurrent stroke (Hazard Ratio (HR) = 1.35, p = 0.006; HR = 1.23, p = 0.014; HR = 1.61, p < 0.001, respectively). The periprocedural acute myocardial infarction rate was 0.3%. Age and Diabetes mellitus were the significant factors to predict periprocedural myocardial infarction (HR = 3.06, p = 0.019; HR = 1.68, p < 0.001, respectively). Periprocedural and overall mortality rates were 1.9% and 17.3%, respectively. The most significant periprocedural mortality risk factor was acute renal failure. Age, diabetes mellitus, acute or chronic renal failure, heart failure, liver disease, and malignancy were factors correlated to the overall period mortality. Conclusion: Periprocedural acute renal failure significantly increased the mortality rate and the number of major adverse cardiovascular events, and the predict power persisted more than one year after the procedure. Age and diabetes mellitus were significant risk factors to predict acute myocardial infarction after carotid artery stenting. [ABSTRACT FROM AUTHOR]