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.

Peri-device leakage not CHA2DS2-VASc is associated with post-left atrial appendage closure cardiovascular event.

OBJECTIVE: In patients with non-valvular atrial fibrillation (NVAF), the left atrial appendage occluder (LAAO) is an alternative treatment for stroke prevention. However, thromboembolic event still occur, and the predictors are unknown. METHODS: The first Asian long-term follow-up study consisted of 308 patients with mean age 71.9±9.5 years, mean CHA2DS2-VASc 4.1 ± 1.8 since 2013. Primary outcome was defined as any type of ischemic stroke/transient ischemic attack (TIA), systemic embolization and cardiovascular death. RESULTS: There was no procedural-related TIA or stroke. After a mean follow-up of 38±16 months, the ischemic stroke/TIA rate was 1.9 and cardiovascular death rate 0.3 per 100 patient-year. The rate of peri-device leak (PDL) was 11.9% and device-related thrombus (DRT) 2.6%. In the multivariable analyses, PDL was the only independent predictor of stroke/TIA (hazard ratio 5.5, p=0.008). CHA2DS2-VASc score, prior history of stroke, DRT and post-procedural anti-thrombotic regimen/duration were not associated with outcomes. Implantation of Watchman was associated with PDL (odds ratio 4.35, p=0.001). CONCLUSIONS: PDL is the only independent predictor of post-LAAO stroke. The risk of stroke for patients with NVAF may be controllable after LAA is occluded, because PDL is preventable and treatable.

2021 TSOC Expert Consensus on the Clinical Features, Diagnosis, and Clinical Management of Cardiac Manifestations of Fabry Disease.

Fabry disease (FD) is an X-linked, rare inherited lysosomal storage disease caused by α-galactosidase A gene variants resulting in deficient or undetectable α-galactosidase A enzyme activity. Progressive accumulation of pathogenic globotriaosylceramide and its deacylated form globotriaosylsphingosine in multiple cell types and organs is proposed as main pathophysiology of FD, with elicited pro-inflammatory cascade as alternative key pathological process. The clinical manifestations may present with either early onset and multisystemic involvement (cutaneous, neurological, nephrological and the cardiovascular system) with a progressive disease nature in classic phenotype, or present with a later-onset course with predominant cardiac involvement (non-classical or cardiac variant; e.g. IVS4+919G>A in Taiwan) from missense variants. In either form, cardiac involvement is featured by progressive cardiac hypertrophy, myocardial fibrosis, various arrhythmias, and heart failure known as Fabry cardiomyopathy with potential risk of sudden cardiac death. Several plasma biomarkers and advances in imaging modalities along with novel parameters, cardiac magnetic resonance (CMR: native T1/T2 mapping) for myocardial tissue characterization or echocardiographic deformations, have shown promising performance in differentiating from other etiologies of cardiomyopathy and are presumed to be helpful in assessing the extent of cardiac involvement of FD and in guiding or monitoring subsequent treatment. Early recognition from extra-cardiac red flag signs either in classic form or red flags from cardiac manifestations in cardiac variants, and awareness from multispecialty team work remains the cornerstone for timely managements and beneficial responses from therapeutic interventions (e.g. oral chaperone therapy or enzyme replacement therapy) prior to irreversible organ damage. We aim to summarize contemporary knowledge based on literature review and the gap or future perspectives in clinical practice of FD-related cardiomyopathy in an attempt to form a current expert consensus in Taiwan.

Usefulness of four-limb blood pressure measurement in prediction of overall and cardiovascular mortality in acute myocardial infarction.

Four-limb blood pressure measurement could improve mortality prediction in the elderly. However, there was no study to evaluate whether such measurement was still useful in predicting overall and cardiovascular (CV) mortality in acute myocardial infarction (AMI). Two hundred AMI patients admitted to cardiac care unit were enrolled. The 4-limb blood pressures, inter-limb blood pressure differences, and ankle brachial index (ABI) were measured using an ABI-form device. The median follow-up to mortality was 64 months (25th-75th percentile: 5-174 months). There were 40 and 138 patients documented as CV and overall mortality, respectively. After multivariable adjustment, the ankle diastolic blood pressure (DBP) on the lower side, ABI value, ABI < 0.9, interarm DBP difference, interankle systolic blood pressure (SBP) and DBP differences, interankle SBP difference ≥ 15 mmHg, and interankle DBP difference ≥ 10 mmHg could predict overall mortality (P ≤ 0.025). The ankle DBP on the lower side, interankle DBP difference, and interankle DBP difference ≥ 10 mmHg could predict CV mortality (P ≤ 0.031). In addition, in the Nested Cox model, the model including the ankle DBP on the lower side and the model including interankle DBP difference had the best value for overall and CV mortality prediction, respectively (P ≤ 0.031). In AMI patients, 4-limb blood pressure measurement could generate several useful parameters in predicting overall and CV mortality. Furthermore, ankle DBP on the lower side and interankle DBP difference were the most powerful parameters in prediction of overall and CV mortality, respectively.

Cardiovascular disease management during the coronavirus disease 2019 pandemic.

Based on clinical presentation, pathophysiology, high infectivity, high cardiovascular involvement, and therapeutic agents with cardiovascular toxicity of coronavirus disease 2019 (COVID-19), regular cardiovascular treatment is being changing greatly. Despite angiotensin-converting enzyme 2 serving as the portal for infection, the continuation of clinically indicated renin-angiotensin-aldosterone blockers is recommended according to the present evidence. Fibrinolytic therapy can be considered a reasonable option for the relatively stable ST segment elevation myocardial infarction (STEMI) patient with suspected or known COVID-19. However, primary percutaneous coronary intervention is still the standard of care in patients with definite STEMI if personal protective equipment is available and cardiac catheterization laboratory has a good infection control. In patients with elevated cardiac enzymes, it is very important to differentiate patients with Type 2 myocardial infarction or myocarditis from those with true acute coronary syndromes because invasive percutaneous intervention management in the former may be unnecessary, especially if they are hemodynamically stable. Finally, patients with baseline QT prolongation or those taking QT prolonging drugs must be cautious when treating with lopinavir/ritonavir and hydroxychloroquine for COVID-19.

2018 TSOC guideline focused update on diagnosis and treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized as a progressive and sustained increase in pulmonary vascular resistance, which may induce right ventricular failure. In 2014, the Working Group on Pulmonary Hypertension of the Taiwan Society of Cardiology (TSOC) conducted a review of data and developed a guideline for the management of PAH.4 In recent years, several advancements in diagnosis and treatment of PAH has occurred. Therefore, the Working Group on Pulmonary Hypertension of TSOC decided to come up with a focused update that addresses clinically important advances in PAH diagnosis and treatment. This 2018 focused update deals with: (1) the role of echocardiography in PAH; (2) new diagnostic algorithm for the evaluation of PAH; (3) comprehensive prognostic evaluation and risk assessment; (4) treatment goals and follow-up strategy; (5) updated PAH targeted therapy; (6) combination therapy and goal-orientated therapy; (7) updated treatment for PAH associated with congenital heart disease; (8) updated treatment for PAH associated with connective tissue disease; and (9) updated treatment for chronic thromboembolic pulmonary hypertension.

Association of renal systolic time intervals with brachial-ankle pulse wave velocity.

Aims: The renal systolic time intervals (STIs), including renal pre-ejection period (PEP), renal ejection time (ET), and renal PEP/renal ET measured by renal Doppler ultrasound, were associated with poor cardiac function and adverse cardiac outcomes. However, the relationship between renal hemodynamic parameters and arterial stiffness in terms of brachial-ankle pulse wave velocity (baPWV) has never been evaluated. The aim of this study was to assess the relationship between renal STIs and baPWV. Methods: This cross-sectional study enrolled 230 patients. The renal hemodynamics was measured from Doppler ultrasonography and baPWV was measured from ABI-form device by an oscillometric method. Results: Patients with baPWV ≧ 1672 cm/s had a higher value of renal resistive index (RI) and lower values of renal PEP and renal PEP/ET (all P< 0.001). In univariable analysis, baPWV was significantly associated with renal RI, renal PEP, and renal PEP/renal ET (all P< 0.001). In multivariable analysis, renal PEP (unstandardized coefficient ß = -3.185; 95% confidence interval = -5.169 to -1.201; P = 0.002) and renal PEP/renal ET (unstandardized coefficient ß = -5.605; 95% CI = -10.217 to -0.992; P = 0.018), but not renal RI, were still the independent determinants of baPWV. Conclusion: Our results found that renal PEP and renal PEP/renal ET were independently associated with baPWV. Hence, renal STIs measured from renal echo may have a significant correlation with arterial stiffness.

The Management and Prognostic Factors of Acute Coronary Syndrome: Evidence from the Taiwan Acute Coronary Syndrome Full Spectrum Registry.

Cardiovascular disease (CVD) accounts for approximately one-third of all global deaths, and acute coronary syndrome (ACS) is the most severe form of CVD. It is of notable importance to develop ACS strategies for reducing major adverse cardiac events (MACE) and preventing complications. In the Taiwan ACS Full Spectrum Registry, 1-year mortality among patients with ST-segment elevation myocardial infarction, non ST-segment elevation myocardial infarction and unstable angina was 6.1%, 10.1%, and 6.2%, respectively. ACS patients with diabetes had significantly worse outcomes in terms of all-cause death and MACE compared to those without diabetes. In-hospital bleeding or chronic kidney disease (CKD) was independently associated with MACE, and ACS patients with both bleeding and CKD had the worst outcome. Use of clopidogrel in conjunction with an invasive strategy could decrease mortality and improve outcomes in the CKD population. CHADS2 and CHA2DS2-VASc scores were useful predictors of subsequent MACE, and renal dysfunction could further improve the prognostic impact of the CHA2DS2-VASc score. For high-risk patients with non-ST-elevation acute coronary syndrome (NSTE-ACS), percutaneous coronary intervention (PCI) within 24-72 hours from symptom onset was demonstrably the optimal time. Suboptimal secondary preventive therapy demonstrated a need for further improvement. The ACS Full Spectrum Registry provided an in-depth analysis of ACS management in Taiwan.

The Current Status of Performing Left Ventriculography in Taiwan.

BACKGROUND: Left ventriculography (LVG) is a gold standard examination of left ventricular function, although it also involves a small but significant risk of complications. However, it was recently reported to be overused in the USA in comparison to an alternative imaging modality. In this study, our aim was to analyze the real-world use of LVG in Taiwan. METHODS: This cohort study analyzed the data in the Taiwan National Health Insurance Bureau database for patients undergoing coronary angiography from 1996-2008. The most recent imaging modalities were used to evaluate left ventricular function including echocardiography and single-photon emission computed tomography (SPECT) within 30-day. The primary outcome was the concomitant use of LVG during coronary angiography. RESULTS: Of 8653 patients who underwent coronary angiography, LVG was performed on 4634 (53.6%) of those study participants. The frequency of LVG use was lower in the groups indicating left ventricular function evaluation, including acute myocardial infarction, heart failure and shock (49.5 vs. 57.1%, p < 0.001). In the population that had undergone a recent left ventricular assessment, the use of LVG was lower (52.2% vs. 54.7%, p = 0.03). Multivariate analysis found that 30-day imaging tests are not a predictor for use of LVG. CONCLUSIONS: In Taiwan, about one half of those patients whose data we reviewed actually received coronary angiography and LVG at the same time. Ultimately, we found that there was no overuse of LVG in those patients with recent alternative imaging modality performed. KEY WORDS: Angiography; Coronary; Ventriculography.

Longitudinal Stent Deformation Caused by Retraction of the Looped Main Branch Guidewire.

A 66-year-old male was treated percutaneously for a bifurcation lesion of the left anterior descending coronary artery by provisional stenting using the jailed wire technique. After successfully stenting the main branch, retraction of the looped main branch guidewire was impossible. After using an intravascular ultrasound we discovered the guidewire was entangled with a stent strut. Thereafter, the proximal stent elongated after retraction. With the support of an over-the-wire microcatheter, we finally pulled out the entrapped guidewire. This rare complication should remind physicians that it is important to prevent the distal guidewire from being looped while retracting it through a stent, regardless of whether it is in the side branch or main vessel. If the guidewire becomes entangled with a stent, a microcatheter or low-profile balloon can be advanced to rescue it before the stent is damaged. Furthermore, the microcather should be maintained after successful retraction of the entangled guidewire to facilitate further wiring and subsequent rescue angioplasty as necessary.

Anemia as an Independent Predictor of Adverse Cardiac Outcomes in Patients with Atrial Fibrillation.

BACKGROUND: Anemia and echocardiographic systolic and diastolic parameters are useful predictors of cardiovascular outcomes in patients with atrial fibrillation (AF). However, no studies have evaluated the use of anemia for predicting cardiovascular outcome in AF patients when the important echocardiographic parameters are known. Therefore, this study was designed to evaluate whether low hemoglobin is a useful parameter for predicting poor cardiac outcome after adjustment for important echocardiographic parameters in AF patients. METHODS: Index beat method was used to measure echocardiographic parameters in 166 patients with persistent AF. Cardiac events were defined as death and hospitalization for heart failure. The association of hemoglobin with adverse cardiac events was assessed by Cox proportional hazards model. RESULTS: The 49 cardiac events identified in this population included 21 deaths and 28 hospitalizations for heart failure during an average follow-up of 20 months (25th-75th percentile: 14-32 months). Multivariable analysis showed that increased left ventricular mass index (LVMI) and decreased body mass index, estimated glomerular filtration rate, and hemoglobin (hazard ratio 0.827; P = 0.015) were independently associated with increased cardiac events. Additionally, tests of a Cox model that included important clinic variables, LVMI, left ventricular ejection fraction, and the ratio of transmitral E-wave velocity to early diastolic mitral annulus velocity showed that including hemoglobin significantly increased value in predicting adverse cardiac events (P = 0.010). CONCLUSIONS: Hemoglobin is a useful parameter for predicting adverse cardiac events, and including hemoglobin may improve the prognostic prediction of conventional clinical and echocardiographic parameters in patients with AF.

Plasma High-Sensitivity C-Reactive Protein Level is Associated with Impaired Estimated Glomerular Filtration Rate in Hypertensives.

BACKGROUND: Both inflammation and chronic kidney disease (CKD) are related to cardiovascular disease. Whether inflammatory biomarkers are associated with impaired glomerular filtration rate (GFR) is unclear in hypertensives. METHODS: We recruited hypertension patients from the cardiovascular clinic of a tertiary medical center in Taiwan. GFR was calculated using the 7-item Modification of Diet in Renal Disease (MDRD) study equation and impaired GFR (IGFR) was defined as GFR less than 60 ml/min/1.73 m(2). High-sensitivity C-reactive protein (hsCRP) kits were used for the measurement of the CRP levels. RESULTS: In our study, 572 consecutive hypertensive patients were enrolled. The range of patient age was 26-91 years (mean 60.5 ± 11.7), and hsCRP and GFR ranged from 0.01 to 9.99 mg/L and 16.6 to 239.6 ml/min//1.73 m(2), respectively. HsCRP levels were correlated with GFR (p = 0.01) and the presence of IGFR (p = 0.009). Multivariate regression analysis showed hsCRP (p = 0.03), age (p < 0.001) and urinary albumin-to-creatinine ratio (UACR) (p = 0.002) are independent factors associated with GFR. Furthermore, hsCRP levels [odds ratio (OR) = 1.16, 95% CI = 1.03-1.31, p = 0.02], age (OR = 1.09, 95% CI = 1.07-1.12, p < 0.001), and UACR (OR = 1.02, 95% CI = 1.01-1.04, p < 0.001) independently predicted the presence of IGFR using binary logistic regression analysis. CONCLUSIONS: Information obtained from our study showed that hsCRP is associated with IGFR in hypertensives. KEY WORDS: Chronic kidney disease; C-reactive protein; Glomerular filtration rate; Hypertension; Inflammation.

Significant Correlation between Brachial Pulse Pressure Index and Renal Resistive Index.

BACKGROUND: The renal resistive index (RI) is calculated as (peak systolic velocity - minimum diastolic velocity)/peak systolic velocity, and has been significantly associated with renal function. Pulse pressure index (PPI) is derived from a formula similar to renal RI, i.e. (systolic blood pressure - diastolic blood pressure)/systolic blood pressure. The purpose of this study was to investigate whether brachial PPI had a significant correlation with renal RI and could be used in identifying patients with impaired renal function. METHODS: We consecutively enrolled 255 patients referred for echocardiographic examination. The renal RI was measured from Doppler ultrasonography and blood pressure was measured from an ABI-form device. RESULTS: Patients with brachial PPI ≥ 0.428 (mean value of brachial PPI) had a lower estimated glomerular filtration rate (eGFR) than those with brachial PPI < 0.428 (p < 0.001). After the multivariate analysis was completed, brachial PPI had a significant correlation with renal RI (unstandardized coefficient ß = 0.53, p < 0.001). The areas under the curve for brachial PPI and renal RI in prediction of eGFR < 45 mL/min/1.73 m(2) were 0.682 and 0.893 (both p < 0.001), respectively. CONCLUSIONS: Brachial PPI was significantly correlated with renal RI. Patients with higher brachial PPI had a more reduced renal function. Hence, brachial PPI may be able to quickly reflect the intrarenal vascular hemodynamics, and may serve as an important tool for screening and follow-up for patients with abnormal renovascular resistance. KEY WORDS: Chronic kidney disease; Pulse pressure index; Resistive index.

The impact of chronic kidney disease on lipid management and goal attainment in patients with atherosclerosis diseases in Taiwan.

BACKGROUND: Patients with chronic kidney disease (CKD) is a very high risk cardiovascular disease population and should be treated aggressively. We investigated lipid management in CKD patients with atherosclerosis in Taiwan. METHODS: 3057 patients were enrolled in a multi-center study (T-SPARCLE). Lipid goal are defined as total cholesterol (TC) < 160mg/dl, low-density lipoprotein (LDL) <100 mg/dl, high-density lipoprotein (HDL) > 40 mg/dl in men, HDL > 50 mg/dl in women, non-HDL cholesterol < 130mg/dl, and triglyceride < 150 mg/dl. RESULTS: Compared with those without CKD (n=2239), patients with CKD (n=818) had more co-morbidities (hypertension, glucose intolerance, stroke and heart failure) and lower HDL but higher triglyceride levels. Overall 2168 (70.5%) patients received lipid-lowering agents. There was similar equivalent statin potency between CKD and non-CKD groups. The goal attainment is lower in HDL and TG in the CKD group as compared with non-CKD subjects (47.1 vs. 51.9% and 63.2 vs. 68.9% respectively, both p < 0.02). Analysis of sex and CKD interaction on goals attainment showed female CKD subjects had lower non-HDL and TG goals attainment compared with non-CKD males (both p < 0.019). CONCLUSION: Although presenting with more comorbidities, the CKD population had suboptimal lipid goal attainment rate as compared with the non-CKD population. Further efforts may be required for better lipid control especially on the female CKD subjects.

Two Consecutive Episodes of Acute Myocardial Infarction Occurring in Different Coronary Arteries of a Single Patient with Sepsis.

UNLABELLED: Although recurrent ST-segment elevation myocardial infarction (STEMI) in the same coronary artery due to acute stent thrombosis has been reported in the literature, there have been no reported cases discussing consecutive STEMI recurring in different coronary arteries in the same patient in one day. Herein, we report an elderly male patient initially suffering from STEMI over the inferior wall who subsequently had another episode of STEMI over the anterior wall within several hours. Despite primary percutaneous coronary intervention being performed over both the right coronary artery and the left anterior descending artery, the patient eventually expired notwithstanding intensive care. This case should caution physicians that consecutive STEMI in different coronary arteries is an extremely rare but still possible medical phenomenon, and could lead to catastrophic clinical outcome. KEY WORDS: Myocardial infarction; Primary percutaneous coronary intervention; Recurrent ST-elevation.

Female showed favorable left ventricle hypertrophy regression during post-TAVR follow-up.

Transcatheter aortic valve replacement (TAVR) is a well-established procedure using a catheter-introduced valve prosthesis for patients with severe aortic stenosis (AS). This retrospective study investigated sex-related differences in pre- and post-TAVR clinical and hemodynamic outcomes and analyzed data of the first 100 cases at Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH) between December 2013 and December 2021. Baseline characteristics, procedural outcomes, mortality rates, and echocardiographic parameters were analyzed and compared between sexes. Among the 100 patients, male (46%) and female (54%) were of similar age (mean age, male 86.0 years vs. female 84.5 years) and of the same severity of AS (mean pressure gradient, male 47.5 mmHg vs. female 45.7 mmHg) at the time receiving the TAVR procedure. Women had smaller aortic valve areas calculated by continuity equation (0.8 ± 0.3 cm2 vs. 0.7 ± 0.2 cm2, p < 0.001). In addition, women had better left ventricle ejection fraction (59.6 ± 14.0% vs. men 54.7 ± 17.2%, p < 0.01). In the post-TAVR follow-up, regression of left ventricle mass and dimension was better in women than in men. None of the patient died within 30 days after the procedure, and women tended to have a more favorable survival than men (2-year mortality and overall mortality rate in 8.3 year, women 9.1% and 22.2% vs. men 22.2% and 34.8%; p = 0.6385 and 0.1277, respectively). In conclusion, the sex-based difference in post-TAVR regression of LV remodeling suggests a need for sex-based evaluation for patients with severe AS and their post TAVR follow-up.

Comparison of antiplatelet and antithrombotic therapy for secondary prevention of ischemic stroke in patients with peripheral artery disease: population-based follow-up study in Taiwan.

BACKGROUND: A limited number of studies have assessed the benefit and risk among the different antiplatelet and antithrombotic therapies in patient with stroke and peripheral artery disease (PAD). We compared the efficacy and safety of clopidogrel, cilostazol, warfarin, and aspirin. METHODS AND RESULTS: A retrospective cohort study analyzing the Taiwan National Health Insurance Research Dataset identified patients with stroke and PAD from 2002 to 2008. Patients were stratified according to their use of aspirin, clopidogrel, cilostazol, warfarin or combination therapy. A total of 1,686 patients were enrolled: aspirin (n=862), clopidogrel (n=92), warfarin (n=136), cilostazol only (n=515), and cilostazol-based combination therapy (n=81). Compared with aspirin, cilostazol could reduce the risk of ischemic stroke [hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.63-0.98, P=0.0349) and no increase in hemorrhagic events (HR 0.98, 95% CI 0.74-1.32, P=0.9122). Clopidogrel decreased the risk of ischemic stroke (HR 0.47, 95% CI 0.29-0.78, P=0.0033) and hemorrhagic events (HR 0.64, 95% CI 0.31-0.96, P=0.034) more than aspirin. There was no statistical difference regarding the risk of stroke and hemorrhagic events among warfarin, cilostazol-based combination therapy and aspirin. CONCLUSIONS: Cilostazol and clopidogrel were more effective in preventing recurrent ischemic stroke without increased hemorrhagic events than aspirin in patients with PAD.

Impact of chronic kidney disease in early invasive versus early conservative revascularization strategies in non-ST-segment elevation acute coronary syndromes: a population-based study from NHIRD of Taiwan.

BACKGROUND: Patients with chronic kidney disease (CKD) sustaining a non-ST-segment elevation acute coronary syndrome (NSTE-ACS) are considered high risk and an early invasive strategy (EIS) is often recommended. However, the impact of CKD on patients receiving an EIS or an early conservative strategy (ECS) is unclear in real-world practice. METHODS: Data were analyzed from the 2005-2008 National Health Insurance Research Database (NHIRD) in Taiwan. The diagnosis of CKD was based on the International Classification of Disease-9 codes recorded by physicians. EIS was defined as coronary angiography with intent to revascularization performed within 72 h of symptom onset. The primary endpoint was time to first major adverse cardiac event (MACE) comprising cardiovascular death, myocardial infarction (MI) and stroke. The secondary endpoints included major bleeding (MB), heart failure (HF) and dialysis during admission (DDA). RESULTS: 834 patients (466 EIS and 368 ECS) were enrolled and age was 64.3 ± 12.6 years. Mean follow-up time was 1,163.96 ± 19.99 days. In the whole population an EIS was associated with a reduction in MACE (HR 0.69; 95% CI 0.50-0.95, p = 0.024) but not in the CKD population (HR 1.08; 95% CI 0.66-1.78, p = 0.76). Kaplan-Meier curves showed CKD subjects receiving an EIS had the highest MACE, HF and DDA rate (all p < 0.019) and CKD subjects receiving an ECS had the highest MB rate (p = 0.018). Cox regression analysis showed CKD predicted higher HF and DDA in those receiving an EIS and higher DDA and MB in those receiving an ECS. CONCLUSION: An EIS reduced MACE in the overall population, and CKD was a poor outcome predictor for both revascularization strategies in NSTE-ACS.

Heart rate significantly influences the relationship between atrial fibrillation and arterial stiffness.

BACKGROUND: Atrial fibrillation (AF) and vascular disease share several risk factors and the two diseases often coexist. Heart rate (HR) is reported to be a major determinant of arterial stiffness. AF patients often have a transiently or persistently rapid HR. Hence, this study was to assess whether AF was significantly associated with arterial stiffness and HR could significantly influence the relationship between AF and arterial stiffness. Besides, we also determine the main correlates of arterial stiffness in AF patients and see whether HR was correlated with arterial stiffness in these patients. METHODS: We included 166 AF and 1336 non-AF patients from subjects arranged for echocardiographic examinations. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). RESULTS: Compared to non-AF patients, AF patients had a higher baPWV (p <0.001). In a multivariate model, including covariates of age, sex, blood pressures and so on, the presence of AF was significantly associated with baPWV (ß = 0.079, P = 0.001). However, further adjustment for HR made this association disappear (ß = 0.005, P = 0.832). In addition to age and systolic blood pressure, increased HR (ß = 0.309, p <0.001) was a major determinant of increased baPWV in our AF patients. CONCLUSIONS: This study demonstrated the presence of AF was associated with increased baPWV, but this association became insignificant after further adjustment for HR, which suggested HR could significantly influence the relationship between AF and baPWV. Besides, HR was positively correlated with arterial stiffness in our AF patients.

Transpulmonary Expression of Exosomal microRNAs in Idiopathic and Congenital Heart Disease-Related Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary artery hypertension (PAH) is a fatal disease characterized by a complex pathogenesis. Exosomes containing microRNAs (miRs) have emerged as a novel biomarker. Transpulmonary exosomal miRs offer valuable insights into pulmonary circulation microenvironments. Hereby, we aimed to explore the potentials of transpulmonary exosomal miRs as differentiating factors between idiopathic PAH and congenital heart disease (CHD)-related PAH. METHODS AND RESULTS: During right heart catheterization, we collected exosomes at pulmonary arteries in 25 patients diagnosed with idiopathic PAH and 20 patients with CHD-related PAH. Next-generation sequencing identified several candidate exosomal miRs. Using quantitative polymerase chain reaction, we validated the expressions of these miRs and revealed significantly elevated expressions of miR-21, miR-139-5p, miR-155-5p, let-7f-5p, miR-328-3p, miR-330-3p, and miR-103a-3p in patients with CHD-related PAH, in contrast to patients with idiopathic PAH. Among these miRs, miR-21 exhibited the highest expression in patients with CHD-related PAH. These findings were further corroborated in an external cohort comprising 10 patients with idiopathic PAH and 8 patients with CHD-related PAH. Using an in vitro flow model simulating the shear stress experienced by pulmonary endothelial cells, we observed a significant upregulation of miR-21. Suppressing miR-21 rescued the shear stress-induced downregulation of the RAS/phosphatidylinositol 3-kinase/protein kinase B pathway, leading to a mitigation of apoptosis. CONCLUSIONS: Our study identified a pronounced expression of transpulmonary exosomal miR-21, particularly in patients with CHD-related PAH, through next-generation sequencing analysis. Further investigation is warranted to elucidate the regulatory mechanisms involving miR-21 in the pathophysiology of PAH.