Application of REVEAL Lite 2 and COMPERA 2.0 risk scores to patients with pulmonary arterial hypertension switching to riociguat in the REPLACE study.

In Riociguat rEplacing PDE5i therapy evaLuated Against Continued PDE5i thErapy (REPLACE) (NCT02891850), improvements in risk status were observed in patients with pulmonary arterial hypertension (PAH) at intermediate risk switching to riociguat versus continuing phosphodiesterase-5 inhibitors (PDE5i). This post hoc study applied the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2 and Comparative Prospective Registry of Newly Initiated Therapies for Pulmonary (COMPERA) 2.0 risk-assessment tools to REPLACE to investigate the impact of baseline risk status on clinical improvement. The proportions of riociguat- and PDE5i-treated patients achieving the primary end-point at REVEAL Lite 2 low, intermediate, and high baseline risk reflected the overall population. Proportions of riociguat-treated patients achieving the primary end-point were comparable between the COMPERA 2.0 intermediate-low risk (39%) and intermediate-high risk (43%) groups. Our findings show that patients in REPLACE achieved clinical improvement by switching from PDE5i to riociguat across all COMPERA 2.0 and most REVEAL Lite 2 baseline risk strata.

Exercise capacity-hemodynamics mismatch in elderly patients with pulmonary hypertension: A nationwide multicenter study from Taiwan Society of Cardiology Pulmonary Hypertension Registry (TAIPANS).

Background: Demographics of pulmonary hypertension (PH) has changed a lot over the past forty years. Several recent registries noted an increase in mean age of PH but only a few of them investigated the characteristics of elderly patients. Thus, we aimed to analyze the characteristics of PH in such a population in this study. Methods: This multicenter study enrolled patients diagnosed with PH in group 1, 3, 4, and 5 consecutively from January 1, 2019 to December 31, 2020. A total of 490 patients was included, and patients were divided into three groups by age (≤45 years, 45-65 years, and >65 years). Results: The mean age of PH patients diagnosed with PH was 55.3 ± 16.3 years of age. There was higher proportion of elderly patients classified as group 3 PH (≤45: 1.3, 45-65: 4.5, >65: 8.1 %; p = 0.0206) and group 4 PH (≤45: 8.4, 45-65: 14.5, >65: 31.6 %; p < 0.0001) than young patients. Elderly patients had shorter 6-min walking distance (6 MWD) (≤45 vs. >65, mean difference, 77.8 m [95% confidence interval (CI), 2.1-153.6 m]), lower mean pulmonary arterial pressure (mPAP) (≤45 vs. >65, mean difference, 10.8 mmHg [95% CI, 6.37-15.2 mmHg]), and higher pulmonary arterial wedge pressure (PAWP) (≤45 vs. 45-65, mean difference, -2.1 mmHg [95% CI, -3.9 to -0.3 mmHg]) compared to young patients. Elderly patients had a poorer exercise capacity despite lower mPAP level compared to young population, but they received combination therapy less frequently compared to young patients (triple therapy in group 1 PH, ≤45: 16.7, 45-65: 11.3, >65: 3.8 %; p = 0.0005). Age older than 65 years was an independent predictor of high mortality for PH patients. Conclusions: Elderly PH patients possess unique hemodynamic profiles and epidemiologic patterns. They had higher PAWP, lower mPAP, and received combination therapy less frequently. Moreover, ageing is a predictor of high mortality for PH patients. Exercise capacity-hemodynamics mismatch and inadequate treatment are noteworthy in the approach of elderly population with PH.

The long-term outcome of chronic thromboembolic pulmonary hypertension: Pulmonary endarterectomy and balloon pulmonary angioplasty.

BACKGROUND: The long-term outcome on patients with chronic thromboembolic pulmonary hypertension (CTEPH) has not been ideal after standard medical treatment. However, good outcome for patients with CTEPH after interventions such as pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA) has been reported recently. The aim of this study was to evaluate the impact of PEA or BPA on long-term outcomes for CTEPH patients in Han-Chinese population. METHODS: This was a multicenter, prospective case-control study. Patients with CTEPH were enrolled between January, 2018 and March, 2020. They were divided into two groups, including intervention (PEA or BPA) and conservative groups. The followed-up period was 26 months after treatment. The endpoints were all-cause mortality and CTEPH mortality. RESULTS: A total of 129 patients were enrolled and assigned to receive PEA/BPA (N = 73), or conservative therapy (N = 56). Overall, the 26-month survival rate of all-cause mortality was significantly higher in intervention group compared to that in conservative group (95.89% vs 80.36%; log-rank p = 0.0164). The similar trend was observed in the 26-month survival rate of CTEPH mortality (97.26% vs 85.71%; log-rank p = 0.0355). Regarding Cox proportional-hazard regression analysis, the hazard ratios (HRs) on patients with CTEPH receiving intervention in the outcome of all-cause mortality and CTEPH mortality were statistically significant (HR = 0.07 and p = 0.0141 in all-cause mortality; HR = 0.11 and p = 0.0461 in CTEPH mortality). CONCLUSION: This multicenter prospective case-control study demonstrated that intervention such as PEA and BPA increased the long-term survival rate for patient with CTEPH significantly. Intervention was an independent factor in long-term outcome for patients with CTEPH, including all-cause mortality and CTEPH mortality.

Induced pluripotent stem cell-derived exosomes attenuate vascular remodelling in pulmonary arterial hypertension by targeting HIF-1α and Runx2.

AIMS: Pulmonary arterial hypertension (PAH) is characterized by extensive pulmonary arterial remodelling. Although mesenchymal stem cell (MSC)-derived exosomes provide protective effects in PAH, MSCs exhibit limited senescence during in vitro expansion compared with the induced pluripotent stem cells (iPSCs). Moreover, the exact mechanism is not known. METHODS AND RESULTS: In this study, we used murine iPSCs generated from mouse embryonic fibroblasts with triple factor (Oct4, Klf4, and Sox2) transduction to determine the efficacy and action mechanism of iPSC-derived exosomes (iPSC-Exo) in attenuating PAH in rats with monocrotaline (MCT)-induced pulmonary hypertension. Both early and late iPSC-Exo treatment effectively prevented the wall thickening and muscularization of pulmonary arterioles, improved the right ventricular systolic pressure, and alleviated the right ventricular hypertrophy in MCT-induced PAH rats. Pulmonary artery smooth muscle cells (PASMC) derived from MCT-treated rats (MCT-PASMC) developed more proliferative and pro-migratory phenotypes, which were attenuated by the iPSC-Exo treatment. Moreover, the proliferation and migration of MCT-PASMC were reduced by iPSC-Exo with suppression of PCNA, cyclin D1, MMP-1, and MMP-10, which are mediated via the HIF-1α and P21-activated kinase 1/AKT/Runx2 pathways. CONCLUSION: IPSC-Exo are effective at reversing pulmonary hypertension by reducing pulmonary vascular remodelling and may provide an iPSC-free therapy for the treatment of PAH.

Application of homocysteine as a non-invasive and effort-free measurements for risk assessment of patients with pulmonary hypertension.

BACKGROUND: Current guideline-recommended multiparameters used to assess the risk levels of pulmonary arterial hypertension (PAH) are invasive hemodynamic measurements or effort-dependent exercise tests. Serum natriuretic peptide is only one kind of effort-free biomarker that has been adopted for risk assessment. This study aimed to investigate the application of homocysteine as a non-invasive and effort-free measurement for the risk assessment of patients with PAH. METHODS: Samples of 50 patients diagnosed with PAH via right heart catheterization were obtained, and the patients were divided into low-, intermediate- and high-risk groups for further analysis. Additionally, serum N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) and homocysteine levels of monocrotaline (MCT)-induced PAH rats were analyzed at each week with progressed severity of PAH, and they were sacrificed on day 28 with pathology being assessed. RESULTS: Hyperhomocysteinemia was an independent predictor (odds ratio [OR]: 1.256; 95% confidence interval [CI]: 1.002-1.574) and showed a linear correlation with NT-proBNP. Hyperhomocysteinemia could discriminate between low/intermediate and high-risk levels in PAH with a cut-off value in 12 µmol/L. Moreover, the elevated homocysteine levels by weeks in MCT rats also demonstrated the association between homocysteine and the severity of PAH. CONCLUSIONS: Homocysteine can be a non-invasive and effort-free risk assessment for patients with pulmonary hypertension. Homocysteine level had a linear correlation with NT-proBNP level, and patients with hyperhomocysteinemia had a higher risk level, higher NT-proBNP level, and decreased lower diffusing capacity for carbon monoxide. The correlation between homocysteine level and PAH severity was also demonstrated in MCT rats.

The impact of end-stage kidney disease on mortality in patients after acute myocardial infarction: A nationwide study.

BACKGROUND: This study aimed to evaluate the impact of end-stage kidney disease (ESKD) on mortality in patients with first-time acute myocardial infarction (AMI). METHODS: This was a retrospective nationwide cohort study. Patients diagnosed with first-time AMI between January 1, 2000, and December 31, 2012, were included. All patients were followed-up until death or December 31, 2012, whichever occurred first. A one-to-one propensity score matching technique was used to match patients with ESKD to those without ESKD of similar sex, age, comorbidities, and coronary intervention (including percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]). Kaplan-Meier cumulative survival curves were constructed to compare AMI patients with and without ESKD. RESULTS: A total of 186 112 patients were enrolled and 8056 patients with ESKD were identified. Propensity score matched 8056 patients without ESKD were included in the comparison. Overall, the 12-year mortality rate was significantly higher in patients with ESKD than in those without ESKD (log-rank p < 0.0001), including the sex, age, and PCI and CABG subgroups. In Cox proportional-hazard regression analysis, ESKD was an independent risk factor for mortality after patients suffered from first-time AMI (hazard ratio, 1.77; 95% CI, 1.70-1.84; p < 0.0001). A forest plot for subgroup analysis revealed that in AMI patients, ESKD had a higher impact on mortality in male; younger age; without comorbidities such as hypertension, diabetes mellitus, peripheral vascular disease, heart failure, cerebrovascular accident, and chronic obstructive pulmonary disease; and receiving PCI and CABG subgroups. CONCLUSION: ESKD significantly increases the mortality risk in patients with first-time AMI, including both sexes, different ages, and whether PCI or CABG was performed. In patients with AMI, ESKD has a high impact on mortality in male, younger age, without comorbidities, and those undergoing PCI and CABG.

2023 Taiwan Society of Cardiology (TSOC) and Taiwan College of Rheumatology (TCR) Joint Consensus on Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.

Background: Pulmonary arterial hypertension (PAH), defined as the presence of a mean pulmonary artery pressure > 20 mmHg, pulmonary artery wedge pressure ≤ 15 mmHg, and pulmonary vascular resistance (PVR) > 2 Wood units based on expert consensus, is characterized by a progressive and sustained increase in PVR, which may lead to right heart failure and death. PAH is a well-known complication of connective tissue diseases (CTDs), such as systemic sclerosis, systemic lupus erythematosus, Sjogren's syndrome, and other autoimmune conditions. In the past few years, tremendous progress in the understanding of PAH pathogenesis has been made, with various novel diagnostic and screening methods for the early detection of PAH proposed worldwide. Objectives: This study aimed to obtain a comprehensive understanding and provide recommendations for the management of CTD-PAH in Taiwan, focusing on its clinical importance, prognosis, risk stratification, diagnostic and screening algorithm, and pharmacological treatment. Methods: The members of the Taiwan Society of Cardiology (TSOC) and Taiwan College of Rheumatology (TCR) reviewed the related literature thoroughly and integrated clinical trial evidence and real-world clinical experience for the development of this consensus. Conclusions: Early detection by regularly screening at-risk patients with incorporations of relevant autoantibodies and biomarkers may lead to better outcomes of CTD-PAH. This consensus proposed specific screening flowcharts for different types of CTDs, the risk assessment tools applicable to the clinical scenario in Taiwan, and a recommendation of medications in the management of CTD-PAH.

Long-term outcomes after stent implantation in very small vessel coronary artery disease.

BACKGROUND: Percutaneous coronary interventions (PCI) in very small vessel lesions represent an intriguing aspect of coronary artery disease (CAD). Uncertainty still exists in stent implantation in very small caliber vessels. This study aimed to evaluate the long-term outcomes of patients treated with 2.0-mm drug-eluting stent (DES). METHOD: This retrospective observational study included 134 patients undergoing PCI with 2.0-mm zotarolimus DES from December 2016 to May 2020. The primary endpoint was major adverse cardiovascular events (MACE) at 2-year follow-up, which was composed of all-cause mortality, target vessel myocardial infarction, and ischemia-driven target lesion revascularization. Multiple logistic regression analysis was used to identify the independent predictors of MACE, and odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULT: The lesions were diffuse (mean length 20.9 ± 5.51 mm) and belong to type B2/C lesions (90.3%). On follow-up, the MACE rate was 20.1% and mostly driven by late lumen loss demanding revascularization (11.9%). In multivariable analysis, chronic kidney disease (CKD) (OR: 4.291, 95% CI: 1.574-11.704, p = 0.004) and calcified lesions (OR: 3.688, 95% CI: 1.311-10.371, p = 0.013) were the independent predictors of subsequent cardiovascular events, whereas statin was associated with better outcomes (OR: 0.335, 95% CI: 0.119-0.949, p = 0.040). CONCLUSION: 2.0-mm DES is a feasible option for treating very small vessel CAD in complex lesions. Patients with CKD and calcified lesions carry the hazard of worse outcomes, and careful consideration should be taken before stenting in this high-risk population.

Impact of medications on outcomes in patients with acute myocardial infarction and chronic obstructive pulmonary disease: A nationwide cohort study.

BACKGROUND: Various inhaled bronchodilators have been associated with cardiovascular safety concerns. This study aimed to investigate the long-term impact of chronic obstructive pulmonary disease (COPD) and the safety of COPD medications in patients after their first acute myocardial infarction (AMI). METHODS: This nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database. Patients hospitalized between 2000 and 2012 with a primary diagnosis of first AMI were included and divided into three cohorts (AMI, ST-elevation myocardial infarction [STEMI], and non-STEMI [NSTEMI]). Each cohort was propensity score matched (1:1) with patients without COPD. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) with 95% CIs. RESULTS: A total of 186 112 patients with AMI were enrolled, and COPD was diagnosed in 13 065 (7%) patients. Kaplan-Meier curves showed that patients with COPD had a higher mortality risk than those without COPD in all cohorts (AMI, STEMI, and NSTEMI). The HR of mortality in AMI, STEMI, and NSTEMI patients with COPD was 1.12 (95% CI, 1.09-1.14), 1.20 (95% CI, 1.14-1.25), and 1.07 (95% CI, 1.04-1.10), respectively. Short-acting inhaled bronchodilators and corticosteroids increased mortality risk in all three cohorts. However, long-acting inhaled bronchodilators reduced mortality risk in patients with AMI (long-acting beta-agonist [LABA]: HR, 0.87; 95% CI, 0.81-0.94; long-acting muscarinic antagonist [LAMA]: HR, 0.82; 95% CI, 0.69-0.96) and NSTEMI (LABA: HR, 0.89; 95% CI, 0.83-0.97; LAMA: HR, 0.80; 95% CI, 0.68-0.96). CONCLUSION: This study demonstrated that AMI patients with COPD had higher mortality rates than those without COPD. Using inhaled short-acting bronchodilators and corticosteroids reduced survival, whereas long-acting bronchodilators provided survival benefits in AMI and NSTEMI patients. Therefore, appropriate COPD medication for acute AMI is crucial.

High Accuracy and Safety of Intraoperative CT-Guided Navigation for Transpedicular Screw Placement in Revision Spinal Surgery.

BACKGROUND: Intraoperative CT-guided navigation (iCT-navigation) has been reported to improve the accuracy and safety of transpedicular screw placement in primary spinal surgery. However, due to a disrupted bony anatomy and scarring tissue, revision spinal surgery can be challenging. The purpose of this study was to evaluate the accuracy and safety of iCT-navigation for screw placement at the virgin site versus the revision site in revision thoracolumbar spinal surgery. METHOD: In total, 254 screws were inserted in 27 revision surgeries, in which 114 (44.9%) screws were inserted at the site with previous laminectomy or posterolateral fusion (the revision site), 64 (25.2%) were inserted at the virgin site, and 76 (29.9%) were inserted to replace the pre-existing screws. CT scans were conducted for each patient after all screws were inserted to intraoperatively confirm the screw accuracy. RESULTS: In total, 248 (97.6%) screws were considered accepted. The rate of accepted screws at the virgin site was 98.4% (63/64) versus 95.6% (109/114) at the revision site (p: 0.422). There were six (2.4%) unaccepted screws, which were immediately revised during the same operation. There was no neurological injury noted in our patients. CONCLUSION: With the use of iCT-navigation, the rate of accepted screws at the revision site was found to be comparable to that at the virgin site. We concluded that iCT-navigation could achieve high accuracy and safety for transpedicular screw placement in revision spinal surgery and allow for the immediate revision of unaccepted screws.

MMP-10 from M1 macrophages promotes pulmonary vascular remodeling and pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by muscularized pulmonary blood vessels, leading to right heart hypertrophy and cardiac failure. However, state-of-the-art therapeutics fail to target the ongoing remodeling process. Here, this study shows that matrix metalloproteinases (MMP)-1 and MMP-10 levels are increased in the medial layer of vessel wall, serum, and M1-polarized macrophages from patients with PAH and the lungs of monocrotaline- and hypoxia-induced PAH rodent models. MMP-10 regulates the malignant phenotype of pulmonary artery smooth muscle cells (PASMCs). The overexpression of active MMP-10 promotes PASMC proliferation and migration via upregulation of cyclin D1 and proliferating cell nuclear antigen, suggesting that MMP-10 produced by infiltrating macrophages contributes to vascular remodeling. Furthermore, inhibition of STAT1 inhibits hypoxia-induced MMP-10 but not MMP-1 expression in M1-polarized macrophages from patients with PAH. In conclusion, circulating MMP-10 could be used as a potential targeted therapy for PAH.

Combination therapy of iPSC-derived conditioned medium with ceftriaxone alleviates bacteria-induced lung injury by targeting the NLRP3 inflammasome.

The lung is the first and most frequent organ to fail among sepsis patients. The mortality rate of sepsis-related acute lung injury (ALI) is high. Despite appropriate antimicrobial therapy, no treatment strategies are available for sepsis-induced ALI. Stem cell-mediated paracrine signaling is a potential treatment method for various diseases. This study aimed to examine the effects of induced pluripotent stem cell-derived conditioned medium (iPSC-CM) combined with antibiotics on ALI in a rat model of Escherichia coli-induced sepsis. Rats were administered either iPSC-CM or the vehicle (saline) with antibiotics (ceftriaxone). After 72 h, liquid biopsy, bronchoalveolar lavage fluid (BALF), and tissues were harvested for analysis. Survival rates were observed for up to 3 days. Furthermore, we examined the effects of iPSC-CM on cytokine production, metalloproteinase 9 (MMP-9) expression, and NLRP3-ASC interaction in RAW264.7 cells stimulated with lipopolysaccharide/interferon-γ (LPS/IFN-γ). Combined treatment of iPSC-CM with antibiotics significantly improved survival in E. coli-infected rats (p = 0.0006). iPSC-CM ameliorated E. coli-induced infiltration of macrophages, reducing the number of cells in BALF, and suppressing interleukin (IL)-1ß, MIP-2, IL-6, and MMP-9 messenger RNA in lung sections. iPSC-CM treatment attenuated NLRP3 expression and inhibited NLRP3 inflammasome activation by disrupting NLRP3-mediated ASC complex formation in LPS/IFN-γ-primed RAW264.7 cells. This study reveals the mechanisms underlying iPSC-CM-conferred anti-inflammatory activity in ALI through the attenuation of macrophage recruitment to the lung, thus inactivating NLRP3 inflammasomes in macrophages. iPSC-CM therapy may be a useful adjuvant treatment to reduce sepsis-related mortality by ameliorating ALI.

The influence of testosterone on the risk of cardiovascular events after percutaneous coronary intervention.

Methods: Between 2015 and 2018, 580 men undergoing PCI at a tertiary referral hospital were divided into low (<3.25 ng/mL) and normal (≥3.25 ng/mL) testosterone groups. Major adverse cardiovascular event (MACE) was defined as the composite outcome of CV death, myocardial infarction, and target lesion revascularization/target vessel revascularization (TLR/TVR) during up to 48 months follow-up after PCI. Results: There were 111 and 469 patients in the low and normal testosterone groups, respectively, with the overall MACE rate of the former being higher than the latter (26.13% vs. 13.01%, p = 0.0006). Moreover, the overall TLR/TVR (20.72% vs. 11.73%, p = 0.0125) and myocardial infarction (3.6% vs. 0.85%, p = 0.0255) rates were significantly higher in those with low serum testosterone who also had a shorter average event-free survival analysis of MACE (25.22 ± 0.88 months) than those with normal testosterone levels (35.09 ± 0.47 months, log-rank p = 0.0004). Multiple logistic regression demonstrated an association between low serum testosterone (<3.25 ng/mL) and a higher MACE rate [odds ratio: 2.06, 95% confidence interval (CI) 1.21-3.51, p = 0.0081]. After adjusting for variables in a Cox regression model, hazard ratios (HRs) for MACE (HR: 1.88, 95% CI: 1.20-2.95, p = 0.0058) and TLR/TVR (HR: 1.73, 95% CI: 1.06-2.83, p = 0.0290) rates were higher in the low testosterone group than those in the normal testosterone group. Conclusion: Low serum testosterone concentrations were associated with a higher risk of MACE and TLR/TVR after PCI than those with normal testosterone levels.

The risk of stroke after acute myocardial infarction in patients with and without atrial fibrillation: A nationwide cohort study.

BACKGROUND: Acute myocardial infarction (AMI) and atrial fibrillation (AF) are risk factors for stroke. The risk of stroke after AMI may differ between patients with and without AF. The aim of this study was to evaluate the impact of AF on stroke in patients after the first AMI. METHODS: This was a retrospective, nationwide cohort study. Patients with a primary diagnosis of a first AMI between 2000 and 2012 were included. All patients were followed up until ischemic stroke or transient ischemic attack (TIA), or December 31, 2012, whichever occurred first. Kaplan-Meier cumulative survival curves were constructed to compare ischemic stroke or TIA between AMI patients with and without AF. RESULTS: A total of 170 472 patients were enrolled in this study. Among them, 8530 patients with AF were identified. The propensity score matching technique was used to match 8530 patients without AF of similar ages and sexes. Overall, the 12-year stroke rate was significantly higher in patients with AF than in those without AF (log-rank p < 0.001), including different sexes, ages, and interventional therapy subgroups. Patients with pre-existing AF had higher stroke rates than those with newly diagnosed AF in male sex, age below 65 years, and those receiving interventional therapy subgroups. In Cox proportional-hazard regression analysis, AF was an independent risk factor for stroke after the first AMI (hazard ratio, 1.67; 95% CI: 1.5-1.87). CONCLUSION: AF significantly increases stroke risk after the first AMI. In patients with AF, those with pre-existing AF have higher stroke risks in male sex, age below 65 years, and those with interventional therapy than those with newly diagnosed AF.

Gene Mutation Annotation and Pedigree for Pulmonary Arterial Hypertension Patients in Han Chinese Patients.

Background: The etiology of pulmonary arterial hypertension (PAH) in the Han Chinese population is poorly understood. Objectives: The aim of this study was to assess gene variants and associated functional annotations for PAH in Han Chinese patients. Methods: This is an ethnicity-based multi-centre study. Blood samples were collected from 20 PAH patients who volunteered for the study, and genetic tests were performed. The DAVID database was used to functionally annotate the genes BMPR2, ALK1, KCNK3, CAV1, and ENG. Associated diseases, functional categories, gene ontology, and protein interactions were analysed using the Functional Annotation Tool in the DAVID database. GEO and ClinVar databases were also used for further comparison with gene mutations in our study. Results: PAH patient with gene mutations were female predominant except for a single male with a BMPR2 mutation. Locus variants in our study included 'G410DfsX1' in BMPR2, 'ex7 L300P,' 'ex4 S110PfsX40,' and 'ex7 E295Afs96X' in ALK1, 'c.-2C>A (IVS1-2 C>A)' in CAV1, and 'ex8 D366Q' in ENG were not found in the ClinVar database associated with PAH. In addition to BMP and TGF-ß pathways, gene ontology of input genes in the DAVID database also included pathways associated with nitric oxide signaling and regulation. Conclusions: This Multi-centre study indicated that 'G410DfsX1' in BMPR2, 'ex7 L300P,' 'ex4 S110PfsX40,' 'ex7 E295Afs96X' in ALK1, 'c.-2C>A (IVS1-2 C>A)' in CAV1, and 'ex8 D366Q' in ENG were identified in Han Chinese patients with PAH. Females were more susceptible to PAH, and a relatively young age distribution was observed for patients with BMPR2 mutations.

Risk Factors and Outcomes of Heart Failure Following First-Episode of Acute Myocardial Infarction-A Case Series Study of 161,384 Cases.

BACKGROUND: Heart failure (HF) is one of the important complications of acute myocardial infarction (AMI), but the epidemiology, associated risks and outcomes have not been well investigated in the era of broad use of fluoroscopy-guided angiographic intervention. METHODS: We analysed 161,384 subjects who had experienced the first episode of AMI during 1 January 2000 and 31 December 2012 using the Taiwan National Health Insurance Research Database. RESULTS: During the index AMI hospitalization, 23.6% of cases developed HF. Female, ≥65 years-old, non-ST-segment elevation type of MI, diabetes mellitus (DM), peripheral vascular occlusion disease (PAOD), chronic obstructive pulmonary disease (COPD), atrial fibrillation, and ventricular tachycardia/fibrillation (VT/VF) were associated with higher risks of developing HF. HF cases had inferior survival outcomes compared to non-HF cases in both the short and long term. Among those HF patients, ≥65 years, DM, PAOD, and VT/VF were associated with worse outcomes. On the contrary, coronary reperfusion intervention and treat-to-target pharmacologic treatment were associated with favourable survival outcomes. CONCLUSIONS: HF remains common in the modern age and poses negative impacts in survival of AMI patients. It highlights that prudent prevention and early treatment of HF during AMI hospitalization is an important medical issue.

Comparison of Different Timing of Multivessel Intervention During Index-Hospitalization for Patients With Acute Myocardial Infarction.

Background: Many patients presenting with acute myocardial infarction (AMI) were found to have a multivessel disease. Uncertainty still exists in the optimal revascularization strategy in AMI patients. The purpose of this study was to assess the outcome of immediate multivessel revascularization compared with staged multivessel percutaneous coronary intervention (PCI) in patients with AMI. Method: This was a nationwide cohort study of 186,112 patients first diagnosed with AMI, 78,699 of whom received PCI for revascularization. Patients who received repetitive PCI during the index hospitalization were referred to as staged multivessel PCI. Immediate multivessel PCI was defined as patients with two-vessel PCI or three-vessel PCI during the index procedure. Cox proportional hazards regression models were performed to evaluate the different indicators of mortality risks in AMI. Result: Immediate multivessel PCI was associated with a worse long-term outcome than staged multivessel PCI during the index admission (log-rank P < 0.001). There was a higher incidence of stroke in patients with multivessel PCI during hospitalization. In Cox analysis, immediate multivessel PCI was an independent risk factor for mortality compared to those with staged multivessel PCI, regardless of the type of myocardial infarction. Conclusion: This study demonstrated that performing immediate multivessel PCI for AMI may lead to worse long-term survival than staged multivessel PCI. Our findings emphasized the importance of PCI timing for non-infarct-related artery stenosis and provided information to supplement current evidence.

Comparison of Long-Term Safety and Efficacy of Bioresorbable Scaffolds between Patients with and without Diabetes Mellitus.

INTRODUCTION: Diabetes mellitus (DM) is a major risk of cardiovascular events. Bioresorbable stent frame materials capable of providing mechanical support and drug-delivery functions have been developed in an attempt to improve long-term outcomes. However, publications about the long-term outcomes of bioresorbable scaffolds (BRS) in DM patients are still limited. The aim of this study was to investigate the long-term safety and efficacy of BRS between patients with and without diabetes. METHODS: Data regarding BRS placement in consecutive patients receiving percutaneous coronary interventions were collected from the cardiovascular center of a single tertiary medical center from 2014 to 2017. RESULTS: A total of 138 cases were included and followed up for 4 years. The mortality rate was 1.1% in the non-diabetic group and 4.1% in the diabetic group (p = 0.2542). No cardiac mortality was observed. One patient had an acute myocardial infarction (0.7%) in the non-diabetic group. The rate of target lesion revascularization was 3.4% in the non-diabetic group and 4.08% in the diabetic group. The ratio of target vessel revascularization was 6.74% in the non-diabetic group and 4.1% in the diabetic group. CONCLUSIONS: This study demonstrated no significant difference in long-term outcomes after BRS implantation between patients with and without diabetes in a single tertiary medical center.

Impact of statin on long-term outcome among patients with end-stage renal disease with acute myocardial infarction (AMI): a nationwide case-control study.

BACKGROUND: Use of statin has been associated with reduced risk of cardiovascular diseases events and mortality. However, in patients with end-stage renal disease (ESRD), the protective effects of statin are controversial. To evaluate the impact of chronic statin use on clinical outcomes of patients with acute myocardial infarction (AMI) with ESRD. METHODS: We enrolled 8056 patients with ESRD who were initially diagnosed and admitted for first AMI from Taiwan's National Health Insurance Research Database. Of which, 2134 patients underwent statin therapy. We randomly selected and use age, sex, hypertension, diabetes mellitus (DM), peripheral vascular diseases (PVD), heart failure (HF), cerebrovascular accidents (CVA), chronic obstructive pulmonary disease, matched with the study group as controls (non-stain user). We compared the effects of statin use in term of all-cause death among patients with AMI with ESRD. RESULTS: Statin use resulted in a significantly higher survival rate in patients ith AMI with ESRD compared with non-statin users. After adjusted the comorbidities the male patients and patients with DM, PVD, HF and CVA had lower long-term survival rate (all p<0.001). Patients who underwent percutaneous coronary intervention (p<0.001), ACE inhibitors/angiotensin II receptor blockers (p<0.001), ß receptor blockers (p<0.001) and statin therapy (p=0.007) had better long-term survival rate. Patients with AMI with ESRD on statin therapy exhibited a significantly lower risk of mortality compared with non-statin users (p<0.0001). CONCLUSION: Among patients with ESRD with AMI, statin therapy was associated with reduced all-cause mortality.