Post-exercise left atrial conduit strain predicted hemodynamic change in heart failure with preserved ejection fraction.

OBJECTIVES: Left ventricle function directly impacts left atrial (LA) conduit function, and LA conduit strain is associated with exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF). Pulmonary capillary wedge pressure (PCWP) before and during exercise is the current gold standard for diagnosing HFpEF. Post-exercise ΔPCWP can lead to worse long-term outcomes. This study examined the correlation between LA strain and post-exercise ΔPCWP in patients with HFpEF. METHODS: We enrolled 100 subjects, including 74 with HFpEF and 26 with non-cardiac dyspnea, from November 2017 to December 2020. Subjects underwent echocardiography, invasive cardiac catheterization, and expired gas analysis at rest and during exercise. Arterial blood pressure, right atrial pressure, pulmonary artery pressure, and PCWP were recorded during cardiac catheterization. Cardiac output, stroke volume, pulmonary vascular resistance, pulmonary artery compliance, systemic vascular resistance, and LV stroke work were calculated using standard formulas. RESULTS: Exercise LA conduit strain significantly correlated with both post-exercise ΔPCWP (r = - 0.707, p < 0.001) and exercise PCWP (r = - 0.659; p < 0.001). Exercise LA conduit strain differentiated patients who did and did not meet the 2016 European Society of Cardiology HFpEF criteria with an area under the curve of 0.69 (95% confidence interval, 0.548-0.831) using a cutoff value of 14.25, with a sensitivity of 0.64 and a specificity of 0.68. CONCLUSIONS: Exercise LA conduit strain significantly correlates with post-exercise ΔPCWP and has a comparable power to identify patients with HFpEF. Additional studies are warranted to confirm the ability of LA conduit strain to predict long-term outcomes among patients with HFpEF. CLINICAL RELEVANCE STATEMENT: Exercise left atrial conduit strain was highly associated with the difference of post-exercise pulmonary capillary wedge pressure and may indicate increased mortality risk in patients with heart failure with preserved ejection fraction, and also has comparable diagnostic ability. KEY POINTS: • Left atrial conduit strain is associated with exercise intolerance in patients with heart failure with preserved ejection fraction. • Left atrial conduit strain during exercise can identify patients with heart failure with preserved ejection fraction. • Exercise left atrial conduit strain significantly correlates with the difference of pulmonary capillary wedge pressure during and before exercise which might predict the long-term outcomes of heart failure with preserved ejection fraction patients.

A non-invasive nomogram for predicting heart failure with preserved ejection fraction in taiwanese outpatients with unexplained dyspnea and fatigue.

BACKGROUND: While Reddy proposed the H2FPEF diagnostic algorithm to aid in diagnosing heart failure with preserved ejection fraction (HFpEF), certain parameters like age and obesity are not suitable for Asian population, especially given the increasing incidence of HFpEF in younger individuals. Therefore, this study aimed to develop an easy-to-use nomogram with non-invasive indices that can be used in outpatient clinics in Taiwan to quickly estimate the probability of HFpEF and help decide whether further invasive cardiopulmonary exercise test (CPET) is needed. METHODS: Outpatients with unexplained dyspnea and fatigue were recruited divided into HFpEF (n = 64) and non-HFpEF (n = 34) groups based on invasive CPET and echocardiography. Multivariate logistic regression analyses identified independent noninvasive variables for developing an HFpEF nomogram. The nomogram's performance was assessed and validated using the concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis. RESULTS: Multivariate logistic regression analyses identified five independent noninvasive variables for developing an HFpEF nomogram, including dyslipidemia (OR = 5.264, p = 0.010), diabetes (OR = 3.929, p = 0.050), left atrial area (OR = 1.130, p = 0.046), hemoglobin <13 g/dL (OR = 5.372, p = 0.010), and NT-proBNP ≥245 pg/mL (OR = 5.108, p = 0.027). The nomogram showed good discriminatory ability (C-index = 0.842) and calibration performance (p = 0.873) and high net benefit (0.1-0.95). Notably, the HFpEF nomogram showed better diagnostic accuracy than the H2FPEF score model in predicting Taiwanese HFpEF patients (AUC: 0.873 vs. 0.608, p = 0.0006). CONCLUSION: The noninvasive HFpEF nomogram provides a preliminary estimation of the probability of HFpEF in Taiwanese outpatients with unexplained dyspnea and fatigue, which may help the decision-making on further invasive CPET.

Long-term outcomes of left atrial appendage occlusion in patients with atrial fibrillation and end stage renal disease.

OBJECTIVE: In patients with atrial fibrillation (AF) and end-stage renal disease (ESRD), oral anticoagulants are contraindicated, and left atrial appendage occlusion (LAAO) is an alternative treatment. However, the efficacy of thromboembolic prevention using LAAO in these patients has rarely been reported in Asian populations. To our knowledge, this is the first long-term LAAO study in patients with AF undergoing dialysis in Asia. METHODS: In this study, 310 patients (179 men) with a mean age of 71.3 ± 9.6 years and mean CHA2DS2-VASc 4.2 ± 1.8 were consecutively enrolled at multiple centers in Taiwan. The outcomes of 29 patients with AF and ESRD undergoing dialysis who underwent LAAO were compared to those without ESRD. The primary composite outcomes were stroke, systemic embolization, or death. RESULTS: No difference in mean CHADS-VASc score was noted between patients with versus without ESRD (4.1 ± 1.8 vs. 4.6 ± 1.9, p = 0.453). After a mean follow-up of 38 ± 16 months, the composite endpoint was significantly higher in patients with ESRD (hazard ratio, 5.12 [1.4-18.6]; p = 0.013) than in those without ESRD after LAAO therapy. Mortality was also higher in patients with ESRD (hazard ratio, 6.6 [1.1-39.7]; p = 0.038). The stroke rate was numerically higher in patients with versus without ESRD, but the difference was not statistically significant (hazard ratio, 3.2 [0.6-17.7]; p = 0.183). Additionally, ESRD was associated with device-related thrombosis (odds ratio, 6.15; p = 0.047). CONCLUSION: Long-term outcomes of LAAO therapy may be less favorable in patients with AF undergoing dialysis, possibly because of the poor condition of patients with ESRD.

2024 Guidelines of the Taiwan Society of Cardiology for the Diagnosis and Treatment of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a multi-organ systemic syndrome that involves cardiac and extra-cardiac pathophysiological abnormalities. Its growing prevalence causes a major public concern worldwide. HFpEF is usually associated with multiple comorbidities, and non-cardiovascular death is common in patients with HFpEF. In Asia, patients with HFpEF has a younger age, higher prevalence of diabetes and chronic kidney disease than Western countries. A 2-step diagnostic algorithm is recommended in this guideline. In the first step, the diagnosis of HFpEF can be made if patients have symptoms and/or signs of heart failure, left ventricular ejection fraction ≥ 50%, increased natriuretic peptide, and objective evidence of left atrial or left ventricular abnormalities or raised left ventricular filling pressure. If diagnosis is still uncertain, invasive or noninvasive stress test can be performed in the second step. Comorbidities need to be controlled in HFpEF. Weight reduction for obesity and supervised exercise training are recommended for HFpEF. For pharmacological therapy, diuretic is used to relieve congestion and sodium-glucose cotransporter 2 inhibitor, empagliflozin or dapagliflozin, is recommended to improve prognosis of HFpEF. The research on HFpEF is advancing at a rapid pace. It is expected that newer modalities for diagnosis and management of HFpEF could appear in the near future.

Copy number variation of gasdermin D gene is associated with atrial fibrillation-related thromboembolic stroke.

AIMS: Atrial fibrillation (AF) is one of the major causes of ischaemic stroke. In addition to clinical risk evaluated by the CHA2DS2-VASC score, the impact of genetic factors on the risk of AF-related thromboembolic stroke has been largely unknown. We found several copy number variations (CNVs) in novel genes that were associated with thromboembolic stroke risk in our AF patients by genome-wide approach. Among them, the gasdermin D (GSDMD) gene was related to inflammation. We aimed to test whether GSDMD deletion was associated with AF-related stroke. METHODS AND RESULTS: A total of 400 patients with documented non-familial AF were selected, of which 100 patients were diagnosed with ischaemic stroke. The baseline characteristics of age, sex, valvular heart disease, coronary artery disease, heart failure, and CHA2DS2-VASc scores were not statistically different between cases and controls. We found that individuals who carried GSDMD homozygous deletion genotype had a higher risk for ischaemic stroke (odds ratio 2.195; 95% confidence interval, 1.24-3.90; P = 0.007), even adjusted by CHA2DS2-VASc scores. We also validated the association of GSDMD with AF stroke in a large Caucasian population (UK Biobank). CONCLUSION: We found a link between the homozygous deletion of the GSDMD gene and an increased risk of stroke in patients with AF. This may implicate the use of therapy targeting GSDMD in the prevention of ischaemic stroke for AF patients.

Impact of post-implantation time on bioresorbable vascular scaffold outcomes for type C versus non-type C coronary lesions: A longer-term study.

BACKGROUND: We have demonstrated that bioresorbable vascular scaffold (BVS) for ACC/AHA type C lesions was associated with higher risks of long-term target lesion revascularization (TLR) and target lesion failure (TLF). We determined the specific time after which higher risks of BVS for type C lesions are reduced in a longer-term follow-up. METHODS: We analyzed data of 457 patients (59 ± 12 years, 87% male) with 714 BVS implanted for 529 lesions and a median follow-up of 56.4 (48.6-62.6) months. Patients with BVS for at least one type C lesion (N = 177) at index intervention and all non-type C lesions (N = 280) were compared for TLF (cardiac death, target vessel myocardial infarction, TLR). We specified the interactions between the non-type C versus type C group and the event-free survival times dichotomized at 24, 30, 32, 33, 36, and 39 months respectively. RESULTS: The type C group had more multivessel disease (86% versus 65%, p < 0.001), left anterior descending artery treated (68% versus 53%, p = 0.002), intravascular imaging used (48% vs. 25%, p < 0.001), and BVS (2.3 ± 0.9 vs. 1.1 ± 0.3, p < 0.001) implanted with a longer total length (57 ± 21 vs. 29 ± 8 mm, p < 0.001). The TLR or TLF was higher (both log-rank p < 0.05) in the type C than in the non-type C group. However, the risks of TLR (hazard ratio: 3.6, 95% CI = 1.1-11.6) and TLF (hazard ratio: 3.8, 95% CI = 1.2-12.1) for type C lesions only remained higher until 24 months post-BVS implantation. CONCLUSION: BVS provides a longer-term advantage, particularly for type C lesions with the majority requiring long stenting.

Impact of Selection Preference on Longer-Term Outcomes between Bioresorbable Vascular Scaffold versus Everolimus-Eluting Stent for True Lumen Tracking-Recanalized Chronic Total Occlusion.

Creation of sizable subintima during intervention for chronic total occlusions (CTO) could lead to the key selection preference of metallic stents rather than bioresorbable vascular scaffolds (BVS) and then possibly deviate the outcome comparisons in real-world studies. By including recanalized CTO with true lumen tracking, we tested if any selection preference remained and compared the outcomes between everolimus-eluting stent (EES) and BVS implantation.Among 211 consecutive CTO interventions with true lumen tracking from August 2014 to April 2018 when BVS was available, we compared the clinical and interventional features between 28 patients with BVS and 77 patients with EES implantation. With propensity score matching and a median follow-up of 50.5 (37.3-60.3) months, we further assessed 25 patients with BVS and 25 with EES for target vessel failure (TVF: cardiac death, target vessel myocardial infarction, and target lesion revascularization).Multivariate analyses showed that BVS was still favored in the presence of LAD CTO (odds ratio (OR) = 3.4, 95% confidence interval (CI) = 1.0-11.7) and an average scaffold/stent size ≥ 3 mm (OR = 10.5, 95% CI = 3.0-37.3). EES was preferred for lesions with a J-CTO score ≥ 3 (OR = 19.3, 95% CI = 3.4-110.8) and multivessel intervention necessary at index procedure (OR = 11.3, 95% CI = 1.9-67.3). With matched comparisons, the TVF-free survival of EES was better than that of BVS for CTO recanalization (P = 0.049 by log-rank test) at long-term follow-up.Even with true lumen tracking techniques, selection bias remained substantial when determining either device for CTO implantation. The matched comparison of outcomes suggested the unfavorable longer-term impacts of the first generation of BVS on CTO lesions.

2023 Consensus of Taiwan Society of Cardiology on the Pharmacological Treatment of Chronic Heart Failure.

The prevalence of heart failure is increasing, causing a tremendous burden on health care systems around the world. Although mortality rate of heart failure has been significantly reduced by several effective agents in the past 3 decades, yet it remains high in observational studies. More recently, several new classes of drugs emerged with significant efficacy in reducing mortality and hospitalization in chronic heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). To integrate these effective therapies and prioritize them in the management of Asian patients, Taiwan Society of Cardiology has recently appointed a working group to formulate a consensus of pharmacological treatment in patients with chronic heart failure. Based on most updated information, this consensus provides rationales for prioritization, rapid sequencing, and in-hospital initiation of both foundational and additional therapies for patients with chronic heart failure.

Lesion impacts on long-term outcomes in patients implanted with bioresorbable vascular scaffold.

BACKGROUND: Bioresorbable vascular scaffold (BVS) had been implanted to several kinds of complex coronary lesions in real-world practice. We tested if long-term outcomes of BVS for complex lesions would be worse than that for relatively simple lesions. METHODS: We analyzed 457 patients (59 ± 12 years, 87% male) with 714 BVS implanted for their 529 lesions and median follow-up of 32.7 (26.8-39.3) months. Complex group (N = 284) was defined as those with BVS for acute coronary syndrome, chronic total occlusion, bifurcation/ostial lesions, instent restenosis/hybrid with metallic stents, diffuse lesions (overlapped by 2 BVS with each â‰§ 18 mm), venous graft/left main lesions, or lesions after rotablation. We compared their outcomes with the remaining 173 patients as non-complex group. RESULTS: The complex group had more chronic kidney disease (7% vs. 2%), multivessel disease (78% vs. 65%), use of intravascular imaging (40% vs. 23%), and more BVS (1.8 ± 0.9 vs. 1.1 ± 0.3) with longer total lengths (47 ± 22 vs. 29 ± 8 mm) implanted than non-complex group (all p < 0.05). However, the long-term target lesion revascularization (TLR) or target lesion failure (TLF) was similar (log rank p > 0.05) between the two groups. Multivariate Cox regression analyses showed BVS for ACC/AHA type C lesions was independently associated with higher risks of TLR (hazard ratio: 2.7, 95% CI = 1.1-6.6) and TLF (hazard ratio: 2.6, 95% CI = 1.1-6.3). CONCLUSION: Comparable outcomes were found between BVS for complex and non-complex lesion category. However, higher risks of TLR and TLF for type C lesions still suggested the prognostic impact of lesion complexity on long-term outcomes of BVS.

Efficacy and safety of balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension.

BACKGROUND: Data on the efficacy and safety of balloon pulmonary angioplasty (BPA) in Taiwanese patients with chronic thromboembolic pulmonary hypertension (CTEPH) are lacking. In this study, we evaluated the effects of BPA on clinical parameters including hemodynamics, echocardiography and functional status in patients with inoperable CTEPH in Taiwan. METHODS: We retrospectively collected the clinical data of inoperable CTEPH patients who underwent ≥3 BPA sessions. Pulmonary hemodynamic parameters of right heart catheterization, echocardiography, 6-min walk distance and World Health Organization (WHO) functional class were collected and analyzed before and after BPA treatment. RESULTS: A total of 59 BPA sessions were performed in 13 inoperable CTEPH patients. No periprocedural deaths or major complications requiring tracheal intubation with mechanical ventilation occurred. WHO functional class significantly improved in all 13 patients (P < 0.001), and 6-min walk distance improved from 344 ± 147 to 450 ± 120 m (P = 0.014). Additionally, the plasma level of N-terminal pro-brain natriuretic peptide significantly decreased (P = 0.007). Hemodynamic data were available in 11 patients after ≥3 BPA sessions. Both mean pulmonary artery pressure and pulmonary vascular resistance significantly decreased from 44.6 ± 11.7 mmHg to 32.6 ± 5.1 mmHg (P = 0.005) and 745 ± 389 dyn·s·cm-5 to 366 ± 120 dyn·s·cm-5 (P = 0.002), respectively. Cardiac output also increased from 3.69 ± 1.12 L/min to 4.33 ± 0.94 L/min (P = 0.021). CONCLUSION: BPA improved both clinical symptoms and hemodynamic data in inoperable CTEPH Taiwanese patients without major periprocedural complications.

The Value of Heart Rhythm Complexity in Identifying High-Risk Pulmonary Hypertension Patients.

Pulmonary hypertension (PH) is a fatal disease-even with state-of-the-art medical treatment. Non-invasive clinical tools for risk stratification are still lacking. The aim of this study was to investigate the clinical utility of heart rhythm complexity in risk stratification for PH patients. We prospectively enrolled 54 PH patients, including 20 high-risk patients (group A; defined as WHO functional class IV or class III with severely compromised hemodynamics), and 34 low-risk patients (group B). Both linear and non-linear heart rate variability (HRV) variables, including detrended fluctuation analysis (DFA) and multiscale entropy (MSE), were analyzed. In linear and non-linear HRV analysis, low frequency and high frequency ratio, DFAα1, MSE slope 5, scale 5, and area 6-20 were significantly lower in group A. Among all HRV variables, MSE scale 5 (AUC: 0.758) had the best predictive power to discriminate the two groups. In multivariable analysis, MSE scale 5 (p = 0.010) was the only significantly predictor of severe PH in all HRV variables. In conclusion, the patients with severe PH had worse heart rhythm complexity. MSE parameters, especially scale 5, can help to identify high-risk PH patients.

Antithrombotic Treatment of Stable Coronary Artery Disease.

Coronary artery disease (CAD) is one of the leading causes of death in Taiwan. Despite the use of current guideline-recommended therapies for secondary prevention, the residual risk of recurrent cardiovascular events remains high in CAD, warranting the need for new treatment options. Antithrombotic drugs are one of the most important medical therapies for CAD. In this article, we review the unmet needs of the current antithrombotic agents and summarize the results of clinical trials with dual antiplatelet therapy in stable CAD. We also review data from a recent study demonstrating the benefits of a dual pathway inhibition strategy with antiplatelet and anticoagulant therapy, a new option for CAD treatment. Finally, we propose a treatment algorithm for choosing different antithrombotic regimens for CAD based on current scientific evidence and expert opinions.

Application of the newest European Association of Cardiovascular Imaging Recommendation regarding the long-term prognostic relevance of left ventricular diastolic function in heart failure with preserved ejection fraction.

OBJECTIVE: The long-term predictive value of the new proposed algorithm in the updated 2016 guidelines of the European Association of Cardiovascular Imaging to assess diastolic dysfunction (DD) in patients with heart failure with preserved ejection fraction (HFpEF) has not been validated. METHODS: The analysis included 451 patients who were diagnosed with HFpEF as confirmed via echocardiography. The endpoints were mortality and hospitalization for HF. The Kaplan-Meier curves and Cox regression models were generated to determine the risk of all-cause mortality based on the 2016 and 2009 DD grading algorithm, respectively. We evaluated the net reclassification index of outcomes on the basis of 2009 DD grade after abiding by the 2016 recommendations. RESULTS: After a follow-up of 2976 days, 119 patients (26.4%) died. According to the 2016 DD grading, grade III DD was associated with a significantly higher risk of mortality (hazard ratio [HR], 2.209; 95% CI 1.144-4.266) and HF hospitalization (HR, 2.047; 95% CI 1.348-3.870), as compared with grade I DD. Grade II DD was also associated with a higher risk of mortality (HR, 1.538; 95% CI 1.313-1.924). However, only grade III DD was independently associated with worse mortality based on 2009 DD grading. The net reclassification index for mortality increased significantly after grading by 2016 algorithm (10.6%, p < 0.001). CONCLUSIONS: The 2016 DD grading algorithm showed improved prognostic value of long-term mortality in patients with HFpEF. Based on the findings of the study, the appropriate grading of DD is important in the prognostication of patients with HFpEF. KEY POINTS: • The application of the 2016 European Association of Cardiovascular Imaging recommendations diastolic dysfunction (DD) grading algorithm improves the predictive value for mortality. • Our analysis suggests DD grades II and III based on 2016 guidelines is associated with poor outcomes as compared with grade I. The echocardiographic indices of the new algorithm should be obtained and applied to effectively evaluate DD.

Is a timely assessment of the hematocrit necessary for cardiovascular magnetic resonance-derived extracellular volume measurements?

BACKGROUND: Cardiovascular magnetic resonance (CMR)-derived extracellular volume (ECV) requires a hematocrit (Hct) to correct contrast volume distributions in blood. However, the timely assessment of Hct can be challenging and has limited the routine clinical application of ECV. The goal of the present study was to evaluate whether ECV measurements lead to significant error if a venous Hct was unavailable on the day of CMR. METHODS: 109 patients with CMR T1 mapping and two venous Hcts (Hct0: a Hct from the day of CMR, and Hct1: a Hct from a different day) were retrospectively identified. A synthetic Hct (Hctsyn) derived from native blood T1 was also assessed. The study used two different ECV methods, (1) a conventional method in which ECV was estimated from native and postcontrast T1 maps using a region-based method, and (2) an inline method in which ECV was directly measured from inline ECV mapping. ECVs measured with Hct0, Hct1, and Hctsyn were compared for each method, and the reference ECV (ECV0) was defined using the Hct0. The error between synthetic (ECVsyn) and ECV0was analyzed for the two ECV methods. RESULTS: ECV measured using Hct1 and Hctsyn were significantly correlated with ECV0 for each method. No significant differences were observed between ECV0 and ECV measured with Hct1 (ECV1; 28.4 ± 6.6% vs. 28.3 ± 6.1%, p = 0.789) and between ECV0 and ECV calculated with Hctsyn (ECVsyn; 28.4 ± 6.6% vs. 28.2 ± 6.2%, p = 0.45) using the conventional method. Similarly, ECV0 was not significantly different from ECV1 (28.5 ± 6.7% vs. 28.5 ± 6.2, p = 0.801) and ECVsyn (28.5 ± 6.7% vs. 28.4 ± 6.0, p = 0.974) using inline method. ECVsyn values revealed relatively large discrepancies in patients with lower Hcts compared with those with higher Hcts. CONCLUSIONS: Venous Hcts measured on a different day from that of the CMR examination can still be used to measure ECV. ECVsyn can provide an alternative method to quantify ECV without needing a blood sample, but significant ECV errors occur in patients with severe anemia.

Prevalence of sudden arrhythmic death syndrome-related genetic mutations in an Asian cohort of whole genome sequence.

AIMS: Recently, the spectrum of background mutation in the genes implicated in sudden arrhythmic death syndrome (SADS), has been elucidated in the Caucasian populations. However, this information is largely unknown in the Asian populations. METHODS AND RESULTS: We assessed the background rare variants (minor allele frequency < 0.01) of major SADS genes in whole genome sequence data of 1514 healthy Taiwanese subjects from the Taiwan Biobank. We found up to 45% of healthy subjects have a rare variant in at least one of the major SADS genes. Around 3.44% of healthy subjects had multiple mutations in one or multiple genes. The background mutation rates in long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and arrhythmogenic right ventricular cardiomyopathy genes were similar, but those in Brugada syndrome (BrS) (SCN5A) and hypertrophic cardiomyopathy (HCM) genes (MYBPC3, MYH7, and TNNT2) were higher, compared to those reported in the Caucasian populations. Furthermore, the rate of incidental pathogenic variant was highest in MYBPC3 gene. Finally, the number of variant was proportional to the exon length of the gene (R2 = 0.486, P = 0.0056) but not related to its functional or evolutionary importance (degree of evolutionary conservation) (R2 = 0.0008, P = 0.9218), suggesting that the mutation was random. The ratio of variant number over exon nucleotide length was highest in MYBPC3, MYH7, and TNNT2 genes. CONCLUSION: Unique features of background SADS gene mutation in the Asian populations include higher prevalence of incidental variant in HCM, BrS, and long QT 3 (SCN5A) genes. HCM genes have the highest variant number per exon length.

The effect and molecular mechanism of statins on the expression of human anti-coagulation genes.

Statins are potent lipid-lowering drugs. Large prospective clinical trials have shown the anti-thrombotic effect of statins, e.g., preventing deep vein thrombosis. However, the mechanism underlying the beneficial effect of statins in reducing thrombus formation remains to be established. We, thus, conduct this study to investigate the potential molecular mechanisms. The cultured human hepatoma cells (HepG2) were used as the in vitro model. The human protein C gene promoter was cloned into the luciferase reporter to study the transcriptional regulation of human protein C gene. Wistar rats fed with simvastatin (5 mg/kg day) were used as the in vivo model. We found that simvastatin increased the expression of protein C in hepatocytes (361 ± 64% and 313 ± 59% after 2 h and 6 h of stimulation, respectively, both p < 0.01). In the animal study, the serum protein C levels were increased in the simvastatin-treated group (7 ± 2.2 unit/ml vs 23.4 ± 19.3 unit/ml and 23.4 ± 18.2 unit/ml and 1 and 2 weeks of treatment, respectively, both p < 0.05). Regarding the possible molecular mechanism, we found that the level of hepatocyte nuclear factor 1α (HNF1α) was also increased in both the in vivo and in vitro models. We found that the protein C promoter activity was increased by simvastatin, and this effect was inhibited by HNF1α knockdown and constitutively active Rac1. Therefore, stains may modulate protein C expression through small GTPase Rac 1 and HNF1α.

Use of calcium channel blockers and myocardial infarction in hypertensive patients with rheumatoid arthritis - A nationwide cohort study.

BACKGROUND/PURPOSE: Rheumatoid arthritis (RA) should be regarded as a high risk factor for myocardial infarction (MI). In addition to anti-hypertensive effect, calcium channel blockers (CCBs) were frequently used as anti-angina drugs in patients with MI. However, the association between CCBs and MI in RA remains unclear. We investigated whether CCBs could decrease incidence of myocardial infarction in patients with hypertension and RA. METHODS: We identified patients from the Registry for Catastrophic Illness, a nation-wide database encompassing almost all of the RA patients in Taiwan from 1995 to 2008. The primary endpoint was MI and the median duration of follow up was 3,050 days. Propensity score matching and Cox proportional hazards regression models were used to estimate hazard ratios for MI. RESULTS: Among 27,844 patients with hypertension, 17,317 (61.5%) subjects received CCBs (mean age = 58.8 years, 72.1% female). The incidence of MI significantly decreased in patients treated with CCBs (hazard ratio [HR] 0.560; 95% confidence interval [CI] 0.494-0.634). After propensity match, subjects receiving CCBs had significantly lower risk of MI (HR 0.637, 95% CI 0.549-0.740). The protective effect of CCBs therapy was significantly better in patients taking longer duration. Of note, the effect remained robust in subgroup analyses, including dihydropyridine CCBs (HR 0.550; 95% CI 0.466-0.650) and non-dihydropyridine CCBs (HR 0.674, 95% CI 0.588-0.773). CONCLUSION: Therapy of CCBs is associated with a lower risk of MI among hypertensive patients with RA. Hence, the prescription of CCBs may be a compelling indication of BP lowering in RA population.

Reduction of blood pressure elevation by losartan in spontaneously hypertensive rats through suppression of LARG expression in vascular smooth muscle cells.

BACKGROUND/PURPOSE: This study sought to elucidate the mechanism by which losartan inhibits blood pressure (BP) elevation in spontaneously hypertensive rats (SHRs). METHODS: Four-week-old Wistar-Kyoto (WKY) rats and SHRs were either treated with losartan (20 mg/kg/day) for 8 weeks or served as untreated controls. BP was measured by the tail-cuff method. At 12 weeks, isometric contraction of the aortic rings of the rats was evaluated with a force transducer and recorder. The mRNA and protein levels of the target Rho guanine nucleotide exchange factors (RhoGEFs), and the extent of myosin phosphatase target subunit 1 (MYPT-1) phosphorylation in the aorta, were determined using quantitative real-time polymerase chain reaction (qPCR) assay and Western blot analysis. RESULTS: The BP of the four-week-old SHRs did not differ from that of the age-matched WKY rats, whereas the BP of the twelve-week-old control group SHRs was higher than that of the control group WKY rats. Losartan treatment, however, inhibited BP elevation in both rat strains, doing so to a greater extent in the treatment group SHRs. The contractile force in response to angiotensin II of the aortic rings from the SHRs treated with losartan was significantly lower than that of the aortic rings from the non-treated SHRs. The protein expression of leukemia-associated RhoGEF (LARG) was significantly higher in the non-treated SHRs compared to the non-treated WKY rats. CONCLUSION: The study results showed that the reduction of BP elevation by losartan in SHRs occurs through the suppression of LARG expression and MYPT-1 phosphorylation in vascular smooth muscle cells.

A performance guide for major risk factors control in patients with atherosclerotic cardiovascular disease in Taiwan.

Atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease, cerebrovascular disease, and peripheral artery disease, carries a high morbidity and mortality. Risk factor control is especially important for patients with ASCVD to reduce recurrent cardiovascular events. Clinical guidelines have been developed by the Taiwan Society of Cardiology, Taiwan Society of Lipids and Atherosclerosis, and Diabetes Association of Republic of China (Taiwan) to assist health care professionals in Taiwan about the control of hypertension, hypercholesterolemia and diabetes mellitus. This article is to highlight the recommendations about blood pressure, cholesterol, and sugar control for ASCVD. Some medications that are beneficial for ASCVD were also reviewed. We hope the clinical outcomes of ASCVD can be improved in Taiwan through the implementation of these recommendations.

Riociguat Improves Pulmonary Hemodynamics in Patients with Inoperable Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Few studies have investigated the effects of riociguat on pulmonary hemodynamics in Asian patients with chronic thromboembolic pulmonary hypertension (CTEPH). In this study, we evaluated the effects of riociguat on pulmonary hemodynamics in inoperable CTEPH patients. METHODS: We retrospectively collected the clinical data of 11 inoperable CTEPH patients. Pulmonary hemodynamic parameters of right heart catheterization, echocardiography, 6-minute walk distance and World Health Organization (WHO) functional class were assessed at baseline and after riociguat treatment. RESULTS: The median duration of riociguat treatment was 12 months, and all 11 patients tolerated riociguat 7.5 mg/day well after titration. With regards to pulmonary hemodynamic data, both mean pulmonary artery pressure and pulmonary vascular resistance significantly decreased from 41 ± 8 mmHg to 38 ± 9 mmHg (p = 0.045) and 787 ± 417 dyn·s·cm-5 to 478 ± 267 dyn·s·cm-5 (p = 0.007), respectively. With regards to clinical symptoms, WHO functional class significantly improved in nine of the 11 patients, and there was no change in the other two patients (p = 0.004). In addition, the median level of N-terminal pro-brain natriuretic peptide also significantly decreased from 281 (117-5943) pg/ml to 226 (48-1276) pg/ml (p = 0.021). CONCLUSIONS: Riociguat treatment improved both clinical symptoms and pulmonary hemodynamics in the inoperative CTEPH patients in this study.