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.

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.

Quality care in ST-segment elevation myocardial infarction.

Over the past decades, the treatment of ST-segment elevation myocardial infarction (STEMI) has been redefined with the incorporation of evidence from multiple clinical trials. Recommendations from guidelines are updated regularly to reduce morbidity and mortality. However, heterogeneous care systems, physician perspectives, and patient behavior still lead to a disparity between evidence and clinical practice. The quality of care has been established and become an integral part of modern healthcare in order to increase the likelihood of desired health outcomes and adhere to professional knowledge. For patients with STEMI, measuring the quality of care is a multifactorial and multidimensional process that cannot be estimated solely based on patients' clinical outcomes. The care of STEMI is similar to the concept of "the chain of survival" that emphasizes the importance of seamless integration of five links: early recognition and diagnosis, timely reperfusion, evidence-based medications, control of cholesterol, and cardiac rehabilitation. Serial quality indicators, reflecting the full spectrum of care, have become a widely used tool for assessing performance. Comprehension of every aspect of quality assessment and indicators might be too demanding for a physician. However, it is worthwhile to understand the concepts involved in quality improvement since every physician wants to provide better care for their patients. This article reviews a fundamental approach to quality care in STEMI.

Pulmonary arterial hypertension in the elderly population.

Pulmonary arterial hypertension (PAH) was a disease predominantly affecting young females about 40 years ago; however, it has been increasingly diagnosed in elderly individuals. Few studies have investigated the features of elderly patients with PAH. This review provides an overview of the characteristics of elderly patients with PAH compared to young patients. The examination of the changing demographics of the population with PAH revealed that the mean age has increased over the years. In addition, the investigation into the diagnostic challenges in elderly patients with PAH revealed the difficulty in differentiating PAH from pulmonary hypertension secondary to diastolic heart failure. Moreover, it was noted that elderly patients underwent combination drug regimens less frequently and exhibited poorer treatment responses than young patients. Finally, it was found that elderly PAH patients experienced poorer survival than young patients. The differences among five survival prediction models and their applicability in predicting the prognosis of PAH patients are discussed.

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.

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.

Comparison of effects of triple antithrombotic therapy and dual antiplatelet therapy on long-term outcomes of acute myocardial infarction.

Warfarin is an alternate choice for patients who are not eligible for non-vitamin K oral anticoagulants after acute myocardial infarction (AMI). This study aimed to compare the long-term outcome of triple antithrombotic therapy (TAT) with that of dual antiplatelet therapy (DAPT) after AMI. This was a nationwide, propensity score-matched, case-control study of 186,112 first AMI patients, of whom 2,825 received TAT comprising aspirin, clopidogrel, and warfarin. Propensity score matching in a ratio of 1:4 by age, sex, comorbidities, and treatment was adopted, Finally, 2,813 AMI patients and 11,252 matched controls that were administered TAT and DAPT (aspirin and clopidogrel), respectively, were included in our analysis. The 12-year overall survival rate did not differ between both strategies (P = .3167). TAT was beneficial in old age (hazard ratio [HR] = 0.92), female sex (HR = 0.86), atrial fibrillation (AF) (HR = 0.80), hypertension (HR = 0.92), cerebrovascular accident (HR = 0.90), and in the absence of percutaneous coronary intervention (HR = 0.79). TAT reduced the rate of recurrent myocardial infarction (P = .0108) but did not affect the rate of stroke (P = .4867), gastrointestinal bleeding (P = .3889), or intracranial hemorrhage (ICH) (P = .3449). TAT reduces the incidence of recurrent myocardial infarction and does not increase the risk of major bleeding, while compared to DAPT.

Management of Pulmonary Arterial Hypertension Patients with World Health Organization Functional Class II.

Pulmonary arterial hypertension (PAH) is an incurable chronic and progressive debilitating disease associated with significant morbidity and mortality. The World Health Organization functional class (WHO FC) at diagnosis and at follow-up remains one of the strongest predictors of survival in PAH. Studies have shown improved long-term outcomes in PAH patients who received PAH-specific treatment, as monotherapy or as combination therapy, early in their disease course. Studies have also shown that without treatment, PAH rapidly deteriorates even in patients with less advanced (low risk) disease state. In this article, we review evidence from randomized controlled clinical trials to support our position on the importance of early PAH management in WHO FC II patients. The growing importance of combination therapy in the early treatment of PAH and recommendations by the most recent guidelines for the diagnosis and treatment of pulmonary hypertension are also discussed in this article.

Combination Therapy with Dipyridamole and Clopidogrel for Secondary Stroke Prevention in Aspirin-Intolerant Patients After Myocardial Infarction: Results of a Nationwide Case-Control Study.

BACKGROUND AND PURPOSE: Combination therapy with dipyridamole and clopidogrel in stroke prevention and long-term outcomes in aspirin-intolerant patients with acute myocardial infarction (AMI) and previous stroke are unknown. This nationwide study analyzed the impact of dipyridamole and clopidogrel on secondary stroke prevention and long-term outcomes in aspirin-intolerant stroke patients after AMI. METHODS: This was a nationwide, case-control study involving 186,112 first AMI patients, 78,607 of whom had a previous history of stroke. In the final analysis, we included 4637 patients taking clopidogrel alone and 208 patients using a combination of clopidogrel and dipyridamole. RESULTS: The 12-year survival rate was not different between clopidogrel and clopidogrel-dipyridamole groups (log-rank p = 0.6247). Furthermore, there were no differences in event-free survival after stroke (log-rank p = 0.6842), gastrointestinal (GI) bleeding (log-rank p = 0.9539), or intracerebral hemorrhage (ICH; log-rank p = 0.6191) between the two groups. Dipyridamole did not contribute significantly to AMI survival (hazard ratio 0.98, 95% confidence interval 0.84-1.15), and did not show benefits in any of the subgroups regardless of sex, age (younger or older than 75 years), comorbidities, percutaneous coronary intervention, or medications. CONCLUSION: No differences were observed in the 12-year survival rate between clopidogrel and clopidogrel-dipyridamole groups. The two groups had balanced event-free survival in recurrent stroke, ICH, GI bleeding, and myocardial infarction.

Comparison of long-term mortality in patients with acute myocardial infarction associated with or without sepsis.

OBJECTIVES: Although the association between systemic infection and cardiovascular events has been identified, uncertainty remains regarding the incidence and prognosis of sepsis in acute myocardial infarction (AMI). The purpose of this research was to assess the impact of sepsis on survival after first AMI. METHODS: This was a nationwide cohort study involving the analysis of data from the Taiwan National Health Insurance Research Database for the period 2000-2012, for patients with a primary diagnosis of first AMI. Among the 186112 prospective patients, sepsis was diagnosed in 13065 (7.0%). The propensity score matching technique was used to match 13065 controls to the patients with sepsis and AMI with similar baseline characteristics. Cox proportional hazards regression models, including sepsis, percutaneous coronary intervention (PCI), and comorbidities, were performed to further evaluate the different influences on the mortality risk in patients hospitalized for first AMI. RESULTS: Overall, the 12-year survival rate was lower in AMI patients with sepsis than in those without sepsis (log rank p-value <0.001); this was also shown in the different age and sex groups. The AMI patients with sepsis had a longer length of hospital stay than those without sepsis (32.5days vs. 11.74 days, p<0.001). In the Cox proportional hazards regression analysis, sepsis was an independent risk factor for mortality in patients after AMI (hazard ratio 1.78; 95% confidence interval 1.72-1.83). Interventional management with PCI or coronary artery bypass grafting improved survival in both the sepsis and non-sepsis patients after first AMI. CONCLUSIONS: In conclusion, sepsis significantly increased the mortality risk of patients after first AMI. PCI may improve the long-term survival of patients in comparison to those managed conservatively.

The Dipyridamole Added to Dual Antiplatelet Therapy in Cerebral Infarction After First Acute Myocardial Infarction: A Nationwide, Case-Control Study.

Background and Purpose: No previous study has compared the impact of dipyridamole-based triple antiplatelet therapy on secondary stroke prevention and long-term outcomes to that of dual antiplatelet therapy (DAPT) in patients with acute myocardial infarction (AMI) and previous stroke. This study aimed to evaluate the impact of dipyridamole added to DAPT on stroke prevention and long-term outcomes in patients with cerebral infarction after first AMI. Methods: This nationwide, case-control study included 75,789 patients with cerebral infarction after first AMI. A 1:4 propensity score matching ratio was adopted based on multiple variables. Finally, the data of 4,468 patients included in the DAPT group and 1,117 patients included in the Dipyridamole-DAPT group were analyzed. Primary outcome was overall survival. Secondary outcomes were cumulative event rate of recurrent MI or stroke, and cumulative intracerebral hemorrhage (ICH) and gastrointestinal bleeding rate. Results: Long-term survival rate was comparable between the two groups (log-rank P = 0.1117), regardless of sex analyses. However, after first year, DAPT subgroup revealed better survival over DAPT-dipyridamole subgroup (log-rank P = 0.0188). In age subgroup analysis, a lower survival rate was detected in younger patients from the Dipyridamole-DAPT group after first year (log-rank P = 0.0151), but no survival difference for older patients. No benefit of Dipyridamole-DAPT was detected for patients after AMI, regardless of the myocardial infarction type. DAPT was superior to Dipyridamole-DAPT in patients who underwent percutaneous coronary intervention (PCI) (log-rank P = 0.0153) and ST elevation myocardial infarction after first year (log-rank P = 0.0019). Dipyridamole-DAPT did not reduce cumulative event rate of recurrent MI or stroke in patients after AMI. Moreover, Dipyridamole-DAPT increased the cumulative ICH rate (log-rank P = 0.0026), but did not affect the cumulative event rate of gastrointestinal bleeding. In Cox analysis, dipyridamole did not improve long-term survival. Conclusions: This nationwide study showed that Dipyridamole-DAPT, compared with DAPT, did not improve long-term survival in patients with stroke after AMI, and was related to poor outcomes after 1 year. Dipyridamole-DAPT did not reduce recurrent rate of MI or stroke, but increased the ICH rate without impacting the incidence of gastrointestinal bleeding.

Chronic Kidney Disease, But Not Diabetes, Can Predict 30-Day Outcomes in Patients with ST-Elevation Myocardial Infarction after Primary Percutaneous Coronary Intervention: A Single-Center Experience.

BACKGROUND: Patients with acute coronary syndrome and impaired renal function have been shown to have high mortality. However, there is scarce literature to date addressing the impact of diabetes mellitus (DM) and renal function on clinical outcomes of ST elevation myocardial infarction (STEMI) in Taiwan. METHOD: This study enrolled 512 STEMI patients who received primary percutaneous coronary intervention. Patients were divided into 4 groups including group 1: patients without DM or CKD (nDM-nCKD); group 2: patients with DM but without CKD (DM-nCKD); group 3: patients with CKD but without DM (nDM-CKD); group 4: patients with DM and CKD (DM-CKD). Patients were also classified into four groups based on their estimated glomerular filtration rates (eGFR): stage 1 (eGFR ≥ 90 ml/min/1.73 m(2), n = 163), stage 2 (eGFR = 89-60 ml/min/1.73 m(2), n = 171), stage 3 (eGFR = 59-30 ml/min/1.73 m(2), n = 136), and stage 4 (eGFR < 30 ml/min/1.73 m(2), n = 42). The complication rates, length of hospital stay, and 30-day outcomes were analyzed. RESULTS: The patients in both the nDM-CKD group and DM-CKD group had higher incidences of hypotension, intra-aortic balloon counterpulsation use, and respiratory failure (p < 0.005). They had significantly longer hospital stay and 30-day mortality rates (p < 0.001). The patients with CKD stage 3 and 4 had longer hospital stay and higher 30-day mortality rates (p < 0.001). However, DM was not an independent factor on the length of hospital stay and 30-day mortality rates. CONCLUSIONS: STEMI patients with impaired renal function, but not DM, had significantly longer hospital stay and higher 30-day mortality rates. KEY WORDS: Chronic kidney disease; Diabetes mellitus; Mortality; Primary percutaneous coronary intervention; ST-segment elevation myocardial infarction.