A risk stratification model modified from the U.S. guideline could be applied in an Asian population with or without ASCVD.

AIM: This study aimed to evaluate the performance of a modified US (MUS) model for risk prediction of cardiovascular (CV) events in Asian patients and compare it to European and Japanese models. MATERIAL AND 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 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.

A cluster of heritable pulmonary arterial hypertension cases in a family with all three siblings carrying the same novel AQP1 c.273C>G variant-a case report.

Approximately 25%-30% of patients diagnosed with idiopathic pulmonary arterial hypertension (PAH) have a clustered underlying Mendelian genetic cause and should be classified as heritable PAH (HPAH). The sixth World Symposium on Pulmonary Hypertension listed AQP1 as a PAH-related gene. AQP1 and its protein product Aquaporin-1 (AQP1) are found in abundance within pulmonary artery smooth muscle cells. Here, we report a family affected by HPAH with all three siblings carrying the same novel missense variant of AQP1 c.273C>G (p.Ile91Met). The youngest brother and the older sister both had dyspnea and edema and were diagnosed with HPAH about 10 years ago. In 2021, they received genetic tests that revealed all three siblings carried the same novel variant of AQP1 (c.273C>G). The brother in between these two siblings, although originally claimed to be asymptomatic, raised awareness. He then sought medical examination and confirmed the diagnosis of HPAH as well. This report on all three siblings carrying the same novel variant of AQP1 (c.273C>G) highlighted the importance of genetic testing and counseling for family members when PAH was first detected.

Association of Major Adverse Cardiac Events and Beta-Blockers in Patients with and without Atherosclerotic Cardiovascular Disease: Long-Term Follow-Up Results of the T-SPARCLE and T-PPARCLE Registry in Taiwan.

Beta-blockers are widely used, but the benefit is now challenged in patients at risk of atherosclerotic cardiovascular disease (ASCVD) in the present coronary reperfusion era. We aimed to identify the risk factors of a major adverse cardiac event (MACE) and the long-term effect of beta-blockers in two large cohorts in Taiwan. Two prospective observational cohorts, including patients with known atherosclerosis cardiovascular disease (T-SPARCLE) and patients with at least one risk factor of ASCVD but without clinically evident ASCVD (T-PPARCLE), were conducted in Taiwan. The primary endpoint is the time of first occurrence of a MACE (cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, and cardiac arrest with resuscitation). Between December 2009 and November 2014, with a median 2.4 years follow-up, 11,747 eligible patients (6921 and 4826 in T-SPARCLE and T-PPARCLE, respectively) were enrolled. Among them, 273 patients (2.3%) met the primary endpoint. With multivariate Cox PH model analysis, usage of beta-blocker was lower in patients with MACE (42.9% vs. 52.4%, p < 0.01). In patients with ASCVD, beta-blocker usage was associated with lower MACEs (hazard ratio 0.72; p < 0.001), but not in patients without ASCVD. The event-free survival of beta-blocker users remained higher during the follow-up period (p < 0.005) of ASCVD patients. In conclusion, in ASCVD patients, reduced MACE was associated with beta-blocker usage, and the effect was maintained during a six-year follow-up. Prescribing beta-blockers as secondary prevention is reasonable in the Taiwanese population.

Case report: The impact of percutaneous atrial septal defect closure in pulmonary hypertension with co-existing cor triatriatum sinister and multiple cardiac comorbidities.

Cor triatriatum sinister is a rare congenital anomaly characterized by the left-sided triatrial form of the heart. Diverse theories have been proposed regarding its formation, and the failure of incorporation of the common pulmonary vein into the left atrium (LA) during embryogenesis is the most widely accepted theory. Accordingly, cor triatriatum sinister may be associated with pulmonary venous obstruction and post-capillary pulmonary hypertension in the setting of restricted fenestration. A high proportion of patients with cor triatriatum sinister also have an associated secundum atrial septal defect. Pre-capillary pulmonary hypertension, which is unusual in patients with small atrial septal defects (<2 cm), is probably not as rare as some reports indicate, especially when combined with complex comorbidities. The conventional treatment strategy of atrial septal defect closure in patients with pulmonary hypertension, whether associated with cor triatriatum sinister or co-existing multiple cardiac anomalies, involves simultaneous repair with other cardiac surgical procedures. To the best of our knowledge, there is no reported clinical experience of percutaneous atrial septal defect closure in the literature. Herein, we present the case of an elderly female with pulmonary hypertension and coexisting cor triatriatum sinister, secundum atrial septal defect, and multiple cardiac anomalies. Despite optimal medical therapy, the biventricular failure deteriorated, and clinical stabilization could not be achieved. Transcutaneous atrial septal defect closure was then performed. Subsequent investigations showed an initial improvement (perhaps due to elimination of the left-to-right shunt) from this intervention, but the long-term impact did not appear favorable, likely due to multiple uncorrected cardiac anomalies. To the best of our knowledge, this is the first clinical report showing that partial treatment of combined pre- and post-capillary pulmonary hypertension by eliminating the pre-capillary component may have an initial benefit; thus, total surgical correction should be considered a definite therapeutic strategy unless contraindicated.

Whole Exome Sequencing of Patients With Heritable and Idiopathic Pulmonary Arterial Hypertension in Central Taiwan.

Background: Genetic variants could be identified in subjects with idiopathic and heritable pulmonary arterial hypertension (PAH). The 6th World Symposium on Pulmonary Hypertension (WSPH) provided a list of genes with evidence of association with PAH. However, reports using whole exome sequencing (WES) from southeastern Asian PAH cohorts were scarce. Methods: Subjects with idiopathic and heritable PAH (N = 45) from two medical centers in central Taiwan were screened for PAH related gene variants. The genomic DNA was prepared from peripheral blood lymphocytes. We performed WES for all patients enrolled in this study. All identified gene variants were validated by polymerase-chain reaction and Sanger sequencing. The clinical and hemodynamic data were compared between bone morphogenetic protein receptor type-2 (BMPR2) gene variants carriers vs. non-carriers. Results: Eight patients (8/45 = 17.8%) was identified carrying BMPR2 gene variants and 8 patients (8/45 = 17.8%) had other WSPH-listed PAH-related gene variants (1 with ACVRL1, 1 with ENG, 1 with SMAD9, 1 with SMAD1, 1 with ATP13A3 and 3 with AQP1). In addition, a total of 14 non-WSPH-listed PAH-related genetic variant sites (ABCC8, NOTCH1, NOTCH2, NOTCH3, JAG1, BMP10, GGCX, FBLN2, ABCA3 and PTGIS) were found in this PAH cohort. Subjects carrying BMPR2 gene variant (N = 8) were younger at diagnosis of PAH (30 ± 11 vs 49 ± 13 years, p = 0.001) than the non-carrier group (N = 37). BMPR2 variant carriers had a trend toward having higher mean pulmonary arterial pressure (PAP) (61 ± 19 vs. 51 ± 13 mmHg, p = 0.076) than the non-carriers upon initial diagnosis. Pulmonary vascular resistance, right atrial pressure, cardiac output, as well as functional class were similar between BMPR2 variant carriers and non-carriers at initial diagnosis. Conclusions: We identified 17.8% of patients with BMPR2 gene variants and 17.8% subjects with other 6th WSPH-listed PAH-related gene variants in a Taiwanese idiopathic and heritable PAH cohort. PAH patients carrying BMPR2 variants presented at a younger age with a trend toward having higher mean PAP at initial diagnosis.

Sustained Hemodynamic and Clinical Improvements for a Patient With Idiopathic Pulmonary Arterial Hypertension Over 1.5 Years After Balloon Atrial Septostomy: A Case Report.

Balloon atrial septostomy (BAS) is an indicated treatment for subjects with idiopathic pulmonary arterial hypertension (IPAH), particularly for those with advanced right heart failure before bridging to lung transplantation. The mid-term clinical and hemodynamic benefits of BAS are not well studied. Here, we present a young female patient with IPAH who received maximal target medication and was admitted to our hospital due to advanced right heart failure. She had transition of subcutaneous to intravenous (IV) prostacyclin analogs (PA) injection and was registered for lung transplantation. The baseline mean right atrium (RA) pressure was 14 mmHg. BAS was performed with a balloon of 6 mm under intracardiac echocardiography (ICE) guidance. Systemic cardiac output (CO) (2.9-3.5 L/min) and oxygen delivery (OD) (291-318 ml/min) both increased after the BAS. Right heart failure was alleviated to function class II. One and a half years later, she received cardiac catheterization again. The second baseline mean RA pressure was 5 mmHg, left atrium (LA) pressure was 2 mmHg, and systemic CO was 3.3 L/min. These data indicated sustained hemodynamic improvements. The second course of BAS was performed under ICE guidance with a balloon of 8 mm. After the second BAS, her RA pressure was 3 mmHg, LA pressure was 3 mmHg, and CO was 3.4 L/min. In conclusion, BAS and IV PA infusion were effective in maintaining mid-term hemodynamic benefits and in stabilizing the critical right heart failure in a patient with IPAH over a 1.5-year period.

Aggressive Afterload Lowering to Improve the Right Ventricle: A New Target for Medical Therapy in Pulmonary Arterial Hypertension?

Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival. Subsequent studies of oral monotherapy or sequential combination therapy demonstrated smaller reductions in mean pulmonary arterial pressure and pulmonary vascular resistance. More recently, retrospective reports of initial aggressive prostanoid treatment or initial combination oral and parenteral therapy have shown marked afterload reduction along with significant improvements in right ventricular function. Some data suggest that reaching threshold levels for pressure or resistance (components of right ventricular afterload) may be key to interrupting the self-perpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved long-term clinical outcomes. Based on these clues, the authors postulate that improved clinical outcomes might be achieved by targeting significant afterload reduction with initial oral combination therapy and early parenteral prostanoids.

Extended-Release Carvedilol in the Treatment of Hypertension: A Double-Blind, Randomized, Placebo-Controlled Trial.

BACKGROUND: Immediate-release carvedilol requires twice-daily dosing and may have low treatment compliance. We assessed the efficacy of a new formulation of once-daily extended-release carvedilol (carvedilol ER) on systolic blood pressure (SBP) and diastolic blood pressure (DBP) among patients with hypertension in this double-blind, randomized, placebo-controlled trial. METHODS: A total of 134 patients with untreated or uncontrolled hypertension were randomly assigned in a 1:1:1 ratio to receive placebo, low-dose carvedilol ER, or high-dose carvedilol ER for 8 weeks. The primary endpoint was the reduction in office SBP at 8 weeks. Secondary endpoints included the reduction in office DBP and the proportion of patients with blood pressure (BP) < 140/90 mm Hg. RESULTS: In the intention-to-treat population, placebo-adjusted changes in SBP/DBP were -2.9 mm Hg [95% confidence interval (CI), -9.6 to 3.7]/-1.7 mm Hg (95% CI, -5.6 to 2.3) and -4.9 mm Hg (95% CI, -11.5 to 1.7)/-3.4 mm Hg (95% CI, -7.3 to 0.5) for low-dose carvedilol ER and high-dose carvedilol ER, respectively. In the per-protocol population, high-dose carvedilol ER was associated with a significant DBP reduction [placebo-adjusted difference, -4.7 mm Hg (95% CI, -8.8 to -0.5); adjusted p = 0.026]. There was a gradational improvement in BP control with carvedilol ER (25%, 37%, and 48% for placebo, low-dose carvedilol ER, and high-dose carvedilol ER, respectively; linear-by-linear association p = 0.028). There were no differences in safety among the three groups. CONCLUSIONS: Carvedilol ER, though well tolerated, did not result in a greater reduction in either SBP or DBP compared with placebo.

Balloon atrial septostomy and transition of subcutaneous to intravenous prostacyclin infusion for rescuing advanced right heart failure in idiopathic pulmonary arterial hypertension: a case report.

BACKGROUND: Intravenous (IV) prostacyclin analogues infusion and balloon atrial septostomy (BAS) are two important treatment options for managing advanced right heart failure in patients with idiopathic pulmonary arterial hypertension (IPAH). References and protocols are rare for dose titrations and transitions between subcutaneous and IV prostacyclin in functional Class IV IPAH patients. Balloon atrial septostomy is rarely done in very few expert centres. CASE SUMMARY: A young female with IPAH who had received maximal medication including subcutaneous prostacyclin analogues injection was admitted due to advanced right heart failure. She received ascites drainage twice. Later, we directly switched the administration route of prostacyclin from subcutaneous to IV at a ratio of 1:1 instantly. Such rapid conversion led her into a state of profound hypotension and drowsy consciousness, which was resolved after escalating IV inotropics and reducing prostacyclin dosage. Five days later, she received BAS under the guidance of intracardiac echocardiography. Her urine output increased and dyspnoea improved gradually. Six months later, clinical worsening happened again with increase of ascites and dyspnoea. She underwent 2nd and 3rd session of graded BAS with relief of symptoms again. She received permanent transition to IV prostacyclin analogues infusions via a peripherally inserted central catheter after three sessions of BAS. DISCUSSION: Balloon atrial septostomy is effective in stabilizing the critical right heart failure in IPAH patients but should be intended as a bridge to lung transplant procedure. Transition from subcutaneous to IV prostacyclin is helpful but needs to be titrated in proper aliquots and time intervals to avoid abrupt haemodynamic changes.

Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension. A Double-Blind Placebo-controlled Clinical Trial.

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56-0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro-brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil-assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12-60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.Clinical trial registered with www.clinicaltrials.gov (NCT01560624).

Sinus Venosus Interatrial Communication, Anomalous Pulmonary Venous Return, Pulmonary Artery Aneurysm With Left Main Compression: Complex Case With Complex Management.

A young female patient was referred for pulmonary arterial hypertension (PAH). Catheterization revealed a large sinus venosus interatrial communication (SVIAC), partial anomalous pulmonary venous return (PAPVR), pulmonary vascular resistance (PVR) 15 Wood units, and bidirectional shunting. She was then put on target medication for PAH. Two years later, she had angina and underwent computed tomography examination, which showed pulmonary arterial aneurysm compressing the left main coronary. Coronary stenting was performed, which successfully relieved the compression and angina. Meanwhile, PVR lowered to 3.5 Wood units after medical therapy. Surgical correction for SVIAC and PAPVR was done successfully 5 years after diagnosis.

Rotavirus is associated with decompensated diarrhea among young rhesus macaques (Macaca mulatta).

Diarrhea with secondary decompensation is the main cause of morbidity and mortality in captive young rhesus macaque (Macaca mulatta) colonies. Approximately 25% of diarrhea cases with secondary decompensation are considered to be idiopathic chronic diarrhea. The purpose of this study was to investigate the suspected but not systematically examined association between rotavirus infection and diarrhea with secondary decompensation among young rhesus macaques at the California National Primate Research Center (CNPRC). Blood and stool samples were collected from 89 randomly selected young animals (age range: 6 months to 1.5 years) and were tested for the presence of rotavirus antibody, and rotavirus antigen, respectively, using enzyme-linked immunosorbent assays (ELISA's). Test and clinical data were analyzed using Fisher's exact tests and multivariate logistic regression model. Our analysis indicates that rotavirus is endemic among young outdoor-housed rhesus macaques at the CNPRC. Although the relationship between detectable rotavirus antigen in stool and symptomatic diarrhea with secondary decompensation was not significant, there was a significant association between rotavirus seropositivity and a history of diarrhea with secondary decompensation within the past 6 months. While our cross-sectional and case-control study suggests an association between rotavirus infection and diarrhea with secondary decompensation among captive rhesus macaques, more extensive longitudinal studies on larger cohorts and with more intensive sample collection are needed to confirm these findings.

Vascular Plugging for the Enlarging Pulmonary Arteriovenous Malformation in a Patient With Idiopathic Pulmonary Artery Hypertension.

The coexistence of idiopathic pulmonary artery hypertension with pulmonary arteriovenous malformation (PAVM) is challenging because although the PAVM causes hypoxia and polycythemia with potential thrombotic complications, closing the PAVM increases pulmonary artery pressure. We report on a lady with PAVM and idiopathic pulmonary artery hypertension who, within 2 years of diagnosis, had an ischemic stroke, PAVM enlargement from 20 × 20 × 30 mm to 30x × 40 × 40 mm and oximetry decrease to 90%. Transcatheter occlusion of PAVM with a vascular plug was successful. A year later, she had no flow via the PAVM and systemic oximetry improved to 97%, but pulmonary vascular resistance increased to 1.5-fold of baseline.

The 2017 Focused Update of the Guidelines of the Taiwan Society of Cardiology (TSOC) and the Taiwan Hypertension Society (THS) for the Management of Hypertension.

Hypertension (HT) is the most important risk factor for cardiovascular diseases. Over the past 25 years, the number of individuals with hypertension and the estimated associated deaths has increased substantially. There have been great debates in the past few years on the blood pressure (BP) targets. The 2013 European Society of Hypertension and European Society of Cardiology HT guidelines suggested a unified systolic BP target of 140 mmHg for both high-risk and low-risk patients. The 2014 Joint National Committee report further raised the systolic BP targets to 150 mmHg for those aged ≥ 60 years, including patients with stroke or coronary heart disease, and raised the systolic BP target to 140 mmHg for diabetes. Instead, the 2015 Hypertension Guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society suggested more aggressive BP targets of < 130/80 mmHg for patients with diabetes, coronary heart disease, chronic kidney disease with proteinuria, and atrial fibrillation patients on antithrombotic therapy. Based on the main findings from the Systolic Blood Pressure Intervention Trial (SPRINT) and several recent meta-analyses, the HT committee members of the Taiwan Society of Cardiology and the Taiwan Hypertension Society convened and finalized the revised BP targets for management of HT. We suggested a new systolic BP target to < 120 mmHg for patients with coronary heart disease, chronic kidney disease with an eGFR of 20-60 ml/min/1.73 m2, and elderly patients aged ≥ 75 years, using unattended automated office BP measurement. When traditional office BP measurement is applied, we suggested BP target of < 140/90 mmHg for elderly patients with an age ≥ 75 years. Other BP targets with traditional office BP measurement remain unchanged. With these more aggressive BP targets, it is foreseeable that the cardiovascular events will decrease substantially in Taiwan.

Consecutive Sessions of Rescue Balloon Atrial Septostomy for an Idiopathic Pulmonary Arterial Hypertension Patient with Refractory Right Heart Failure - Usefulness of Intracardiac Echocardiography Guidance.

For idiopathic pulmonary artery hypertension (PAH) patients with end-stage right heart failure who received maximal medical therapy, balloon atrial septostomy (BAS) is recommended by most guidelines as a palliative therapy or a bridging treatment before lung transplantation. In this report, we described a 32-year-old woman with idiopathic PAH, who received maximal PAH-specific medical treatment, including intravenous prostacyclin, but still suffered from refractory right heart failure. The markedly enlarged right atrium (RA), high mean RA pressure of 23 mmHg, low systemic arterial oxygen saturation of 86% and concomitant pancytopenia all increased the patient's risk for BAS. We used intracardiac echocardiography (ICE) guidance to facilitate trans-septal puncture, and performed graded BAS four times within 7 months to stabilize the patient. Our case showed that with dedicated PAH treatment, an experienced structural heart interventionist and ICE guidance, BAS could be done safely even in a patient in unfavorable clinical and hemodynamic condition.

Familial clustering of congenital deafness, patent ductus arteriosus, Eisenmenger complex, and differential cyanosis: A case report.

RATIONALE: Few studies had reported syndromes that include patent ductus arteriosus (PDA) with Eisenmenger syndrome and congenital deafness clustered in male siblings without facial, skeletal, or mental abnormalities. PATIENT CONCERNS: Two brothers, who were deaf and had PDA with Eisenmenger complex, were first seen at our Cardiology clinic at the ages of 25 and 41, respectively. They presented with progressive dyspnea on exertion. Upon physical examination, both brothers had clubbing and/or cyanotic toes, normal fingers, and without facial, skeletal, ophthalmological, or mental abnormalities. DIAGNOSES AND INTERVENTIONS: Echocardiography and multidetector computed tomography revealed large PDAs in both brothers. Cardiac catheterization showed bidirectional shunting via the PDA. OUTCOMES AND LESSONS: Familial clustering of Eisenmenger PDA and congenital deafness is rare. Further studies are warranted to define possible genetic links.

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Assess the Efficacy and Safety of Ethyl-Ester Omega-3 Fatty Acid in Taiwanese Hypertriglyceridemic Patients.

AIM: Information regarding the effects of omega-3 fatty acid on hypertriglyceridemic patients in Chinese is still limited. This study aimed to investigate the efficacy and safety of Omacor®, a prescription ethyl-ester omega-3 fatty acid for the treatment of hypertriglyceridemia, administered at doses of 2 g/day and 4 g/day to Taiwanese hypertriglyceridemic patients. METHODS: A multicenter, randomized, double-blind, placebo-controlled, parallel study in adults with hypertriglyceridemia was conducted. After a five-week diet lead in period patients with triglycerides =200-1000 mg/dL were randomized to receive Omacor®, a concentrated preparation of omega-3 eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) in a dose of 1 g twice daily (2 g Omacor®), 2 g twice daily (4 g Omacor®) or placebo, for eight weeks. The primary endpoint was the percentage change in triglyceride serum levels from baseline to the end of treatment. RESULTS: A total of 253 Taiwanese patients were randomized, of which 65.6% (166) were men. At the end of the treatment, the percentage change in triglyceride serum levels in both the Omacor® 4 g/day (－32.1%) and 2 g/day (－29.7%) groups was larger than in the placebo group (－5.4%) (p＜0.001). The incidence of drug-related adverse events was as follows: 0.0%, 1.2%, and 0.0% in Omacor® 4 g/day, Omacor® 2 g/day, and placebo groups, respectively. No drug-related serious adverse events were reported during the study. CONCLUSIONS: Omacor® may be a feasible option to treat hypertriglyceridemia in Taiwanese patients.

Atrial fibrillation, liver disease, antithrombotics and risk of cerebrovascular events: A population-based cohort study.

BACKGROUND: Whether patients with atrial fibrillation (AF) and liver disease are also prone to cerebrovascular events and respond similarly favorably to antithrombotic therapy remains under-investigated. METHODS: Patients ≥18years with newly-diagnosed AF in the period 2005 to 2009 were scrutinized from the "Longitudinal Health Insurance Database 2005" (1 million beneficiaries) of Taiwan's National Health Insurance Institute. Patients were categorized into the Liver (N=433) or the Non-liver (N=3490) cohort according to whether they had a diagnosis of advanced liver disease. Patients were then followed to determine cumulative incidence of hospitalization-requiring cerebrovascular events, preventive effects of antithrombotics, and predictors of cerebrovascular events by Cox regression analysis. RESULTS: Within a mean follow-up of 3.3±1.4years, ischemic stroke (89.2 vs. 50.3 per 1000 person-years, adjusted HR 1.502, 95% CI 1.207-1.868, p<0.001) and overall cerebrovascular events (102.3 vs. 56.4 per 1000 person-years, adjusted HR 1.535, 95% CI 1.251-1.883, p<0.001) occurred significantly more often in the Liver than in the Non-liver cohort. Cox models identified aging (≥65years), DM, and CHA2DS-VASc score≥2 points as risk factors for overall cerebrovascular events in the Liver cohort, whereas antiplatelet agents (HR 0.932, 95% CI 0.128-6.803, p=NS) and vit-K antagonistic anticoagulants (HR 1.087, 95% CI 0.150-7.862, p=NS) showed no correlation. CONCLUSION: AF patients comorbid with advanced liver disease are more vulnerable to ischemic and therein overall cerebrovascular events, especially in those with old age, DM, or high CHA2DS-VASc scores. This propensity to cerebrovascular events, however, can't be altered by antithrombotic therapy.

Left Main Coronary Artery Stenting to Relieve Extrinsic Compression by a Giant Pulmonary Artery Aneurysm in a Patient with Idiopathic Pulmonary Artery Hypertension.

Pulmonary artery aneurysm (PAA) is a rare but lethal disease. We present a female patient with idiopathic pulmonary artery hypertension (IPAH)-related PAA, who suffered from unstable angina pectoris. Multi-detector computed tomography and coronary angiogram revealed extrinsic compression of the left main coronary artery (LMCA) caused by a giant PAA with severe ostial stenosis. Intravascular ultrasound showed an oval-shaped ostium of the LMCA, indicating extrinsic compression. After successful LMCA stent implantation, chest pain was greatly relieved. This case illustrates that beyond right ventricle ischaemia and coronary atherosclerotic disease, LMCA compression by PAA should be considered in the differential diagnosis of angina in patients with IPAH related PAA. In addition, intravascular ultrasound can be used to confirm the diagnosis and guide the stent implantation safely.

Combination With Low-dose Dextromethorphan Improves the Effect of Amlodipine Monotherapy in Clinical Hypertension: A First-in-human, Concept-proven, Prospective, Dose-escalation, Multicenter Study.

The combination of low rather than high dose of dextromethorphan (DXM) with amlodipine (AM) could improve blood pressure (BP) reduction in hypertensive animals. The study aimed to evaluate the feasibility of different doses of DXM combined with standard AM treatment in clinical hypertension.This was a prospective, 14-week, dose-escalation, multicenter study. After 2-week run-in period with AM 5 mg/day, hypertensive patients who got the BP goal of 140/90 mmHg kept receiving AM monotherapy for another 12 weeks. The nonresponders, while kept on AM 5 mg/day, received additional DXM treatment for 3 sequential dose-titrated periods with initially 2.5 mg/day, followed by 7.5 mg/day, and finally 30 mg/day. Each period was for 4 weeks. The patients at BP goal after each treatment period were defined as the responders and kept on the same combination till the end of the study. The responder rate of each treatment period was recorded. The changes of BP and serum antioxidant/endothelial markers between week 14 and week 2 were evaluated.Of the 103 patients initially enrolled, 89 entered the treatment period. In the 78 patients completing the study, 31 (40%) at BP goal after 2-week AM run-in kept on AM monotherapy (DXM0). The addition of 2.5 (DXM2.5) and 7.5 mg/day (DXM7.5) of DXM enabled BP goal achievement in 22 (47%) nonresponders to AM monotherapy including 16 (29%) with DXM2.5 and 6 (18%) with DXM7.5. Only 4 patients (16%) reached BP goal with the combination of DXM 30 mg/day (DXM30). Overall, 73% of the 78 patients reached BP goal at the end of the 14-week study. Mean systolic BP was reduced by 7.9% ±â€Š7.0% with DXM2.5 (P < 0.001) and by 5.4% ±â€Š2.4% with DXM7.5 (P = 0.003) respectively at week 14 from that at week 2, which was unchanged in either DXM0 or DXM30 group. Besides, the effects of combination treatment were particularly significant in the patients with impaired endothelial function suggested by reduced serum NOx level at baseline.Accordingly, the combination with low dose of DXM was feasible to improve BP control in patients who failed to achieve the BP goal by standard AM monotherapy. The benefit effects might be significant especially in patients with impaired endothelial function.