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.

Factors affecting the intensity of chronic musculoskeletal pain in patients with cardiovascular disease and evaluation of the efficacy of magnesium emulsion cream for muscle cramps.

Chronic musculoskeletal pain (CMP) is associated with an increased risk of cardiovascular disease (CVD). This study aimed to determine the factors associated with the intensity of CMP in patients with underlying CVD and to evaluate the efficacy of Ice Power Magnesium In Strong Cream in patients with muscle cramps. We investigated 396 patients with or without CMP who visited an outpatient cardiology clinic and analyzed the features of CMP and factors associated with pain intensity and specific types of CVD in study 1. We also analyzed 73 patients who had muscle cramps in the lower extremities in study 2 to evaluate the efficacy of Ice Power Magnesium In Strong Cream in reducing pain intensity. In study 1, multivariable linear regression analysis showed that older age (regression coefficient [B] = 0.66, 95% confidence interval [CI], 0.07-1.24), female sex (B = 1.18, 95% CI, 0.59-1.76), presence of hypertension (B = 0.69, 95% CI, 0.05-1.33), and use of calcium supplements (B = 1.27, 95% CI, 0.31-2.24) were significantly associated with a higher intensity of CMP. In study 2, the mean pain scores at baseline, week 2 and week 4 after treatment were 5.99 ± 2.12, 2.92 ± 2.63, and 1.90 ± 2.41, respectively, and the reductions were significant at both week 2 and week 4 after treatment (P < .05). Older age, female sex, hypertension, and use of calcium supplements were associated with an increased intensity of CMP. Ice Power Magnesium In Strong Cream was effective in reducing the pain intensity of muscle cramps in the lower extremities.

Long-Term Survival of Patients with Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: A Single-Center Cohort.

Pulmonary arterial hypertension (PAH) is a rare but severe complication of connective tissue disease (CTD). CTD-associated PAH (CTD-PAH) is the most common subgroup of PAH in East Asia. We prospectively collected 41 patients with CTD-PAH and followed them for a mean period of 43 ± 36 months. The long-term survival rates of the CTD-PAH patients at 1, 2, 3 and 5 years were 90%, 80%, 77%, and 60%, respectively. The non-survivors had more dilated main pulmonary arteries, higher pulmonary artery pressure and pulmonary vascular resistance (PVR). PAH-specific therapy resulted in improvements in functional class, 6-minute walk distance, serum uric acid, right ventricular function and PVR. Increased C-reactive protein during follow-up, indicating inflammatory processes, was also crucial for the management of CTD-PAH. Therefore targeting both PAH and inflammation is important in this specific subgroup of PAH. The results of this study may help develop treatment strategies for CTD-PAH patients.

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.

Quality of Life in Patients With Pulmonary Hypertension.

We explored positive and negative affect, quality of life (QOL), and associated factors in patients with pulmonary hypertension. We conducted this cross-sectional study using convenience sampling at a medical center in Taiwan. We used the Social Support Scale, positive and negative affect scale, and Short Form 36-item Health Survey to collect data. In these patients, greater social support was associated with less negative affect and better QOL (mental components). Lower Borg dyspnea scores or greater distances in the six-minute walk test were associated with more positive affect, less negative affect, and better QOL (both physical and mental components). Patients with less negative affect and more positive affect had better QOL (mental components). Therefore, nursing staff should routinely monitor the emotional status and QOL of patients with pulmonary hypertension, especially those with less social support and poorer cardiopulmonary function. Strengthening these aspects may improve patients' emotional status and QOL.

Cathepsin S Inhibition Suppresses Experimental Systemic Lupus Erythematosus-Associated Pulmonary Arterial Remodeling.

Patients with systemic lupus erythematosus (SLE) associated with pulmonary arterial hypnertension (PAH) receive targeted therapy for PAH to decrease pulmonary arterial systolic pressure and significantly prolong their survival. Cysteine cathepsin proteases play critical roles in the progression of cardiovascular disease. Inhibition of cathepsin S (Cat S) has been shown to improve SLE and lupus nephritis. However, the effect of Cat S inhibitors on SLE-associated PAH (SLE-PAH) remains unclear, and there is no animal model for translational research on SLE-PAH. We hypothesized that the inhibition of Cat S may affect PAH development and arterial remodeling associated with SLE. A female animal model of SLE-PAH, female MRL/lpr (Lupus), was used to evaluate the role of pulmonary arterial remodeling in SLE. The key finding of the research work is the establishment of an animal model of SLE associated with PAH in female MRL/lpr mice that is able to evaluate pulmonary arterial remodeling starting from the age of 11 weeks to 15 weeks. Cat S protein level was identified as a marker of experimental SLE. Pulmonary hypertension in female MRL/lpr (Lupus) mice was treated by administering the selective Cat S inhibitor Millipore-219393, which stimulated peroxisome proliferator-activated receptor-gamma (PPARγ) in the lungs to inhibit Cat S expression and pulmonary arterial remodeling. Studies provide an animal model of female MRL/lpr (Lupus) associated with PAH and a deeper understanding of the pathogenesis of SLE-PAH. The results may define the role of cathepsin S in preventing progressive and fatal SLE-PAH and provide approaches for therapeutic interventions in SLE-PAH.

Gut Microbiota and Bile Acids Mediate the Clinical Benefits of YH1 in Male Patients with Type 2 Diabetes Mellitus: A Pilot Observational Study.

Our previous clinical trial showed that a novel concentrated herbal extract formula, YH1 (Rhizoma coptidis and Shen-Ling-Bai-Zhu-San), improved blood glucose and lipid control. This pilot observational study investigated whether YH1 affects microbiota, plasma, and fecal bile acid (BA) compositions in ten untreated male patients with type 2 diabetes (T2D), hyperlipidemia, and a body mass index ≥ 23 kg/m2. Stool and plasma samples were collected for microbiome, BA, and biochemical analyses before and after 4 weeks of YH1 therapy. As previous studies found, the glycated albumin, 2-h postprandial glucose, triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels were significantly improved after YH1 treatment. Gut microbiota revealed an increased abundance of the short-chain fatty acid-producing bacteria Anaerostipes and Escherichia/Shigella. Furthermore, YH1 inhibited specific phylotypes of bile salt hydrolase-expressing bacteria, including Parabacteroides, Bifidobacterium, and Bacteroides caccae. Stool tauro-conjugated BA levels increased after YH1 treatment. Plasma total BAs and 7α-hydroxy-4-cholesten-3-one (C4), a BA synthesis indicator, were elevated. The reduced deconjugation of BAs and increased plasma conjugated BAs, especially tauro-conjugated BAs, led to a decreased glyco- to tauro-conjugated BA ratio and reduced unconjugated secondary BAs. These results suggest that YH1 ameliorates T2D and hyperlipidemia by modulating microbiota constituents that alter fecal and plasma BA compositions and promote liver cholesterol-to-BA conversion and glucose homeostasis.

Levosimendan use in patients with acute heart failure and reduced ejection fraction with or without severe renal dysfunction in critical cardiac care units: a multi-institution database study.

BACKGROUND: Acute heart failure is a life-threatening clinical condition. Levosimendan is an effective inotropic agent used to maintain cardiac output, but its usage is limited by the lack of evidence in patients with severely abnormal renal function. Therefore, we analyzed data of patients with acute heart failure with and without abnormal renal function to examine the effects of levosimendan. METHODS: We performed this retrospective cohort study using data from the Chang Gung Research Database (CGRD) of Chang Gung Memorial Hospital (CGMH). Patients admitted for heart failure with LVEF ≤ 40% between January 2013 and December 2018 who received levosimendan or dobutamine in the critical cardiac care units (CCU) were identified. Patients with extracorporeal membrane oxygenation (ECMO) were excluded. Outcomes of interest were mortality at 30, 90, and 180 days after the cohort entry date. RESULTS: There were no significant differences in mortality rate at 30, 90, and 180 days after the cohort entry date between the levosimendan and dobutamine groups, or between subgroups of patients with an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 and eGFR < 30 mL/min/1.73 m2 or on dialysis. The results were consistent before and after propensity score matching. CONCLUSIONS: Levosimendan did not increase short- or long-term mortality rates in critical patients with acute heart failure and reduced ejection fraction compared to dobutamine, regardless of their renal function. An eGFR less than 30 mL/min/1.73 m2 was not necessarily considered a contraindication for levosimendan in these patients.

Regulation of a Cytochrome P450 Gene CYP94B1 by WRKY33 Transcription Factor Controls Apoplastic Barrier Formation in Roots to Confer Salt Tolerance.

Salinity is an environmental stress that causes decline in crop yield. Avicennia officinalis and other mangroves have adaptations such as ultrafiltration at the roots aided by apoplastic cell wall barriers to thrive in saline conditions. We studied a cytochrome P450 gene from A. officinalis, AoCYP94B1, and its putative ortholog in Arabidopsis (Arabidopsis thaliana), AtCYP94B1, which are involved in apoplastic barrier formation. Both genes were induced by 30 min of salt treatment in the roots. Heterologous expression of AoCYP94B1 in the atcyp94b1 Arabidopsis mutant and wild-type rice (Oryza sativa) conferred increased NaCl tolerance to seedlings by enhancing root suberin deposition. Histochemical staining and gas chromatography-tandem mass spectrometry quantification of suberin precursors confirmed the role of CYP94B1 in suberin biosynthesis. Using chromatin immunoprecipitation and yeast one-hybrid and luciferase assays, we identified AtWRKY33 as the upstream regulator of AtCYP94B1 in Arabidopsis. In addition, atwrky33 mutants exhibited reduced suberin and salt-sensitive phenotypes, which were rescued by expressing 35S::AtCYP94B1 in the atwrky33 background. This further confirmed that AtWRKY33-mediated regulation of AtCYP94B1 is part of the salt tolerance mechanism. Our findings may help efforts aimed at generating salt-tolerant crops.

Outcomes of Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary Hypertension at a Single Center in Taiwan.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group IV pulmonary hypertension. This study aimed to report our institutional experience in managing CTEPH. METHODS: We prospectively collected the data of 23 patients diagnosed with CTEPH between August 2001 and August 2017 in Linkou Chang Gung Memorial Hospital. Baseline characteristics including functional class (FC), 6-minute walk distance (6MWD), comorbidities, hematological and biochemical data, echocardiography, cardiac catheterization, and selective pulmonary angiography were recorded at diagnosis. All patients were referred to a cardiac surgeon for pulmonary endarterectomy (PEA) assessment. RESULTS: The mean age at diagnosis was 48.4 ± 16.1 years. Nineteen patients (83%) underwent PEA with mean postoperative follow-up of 37.7 ± 42.8 months. The in-hospital mortality rate of PEA was 11%. The 1-, 2-, 3- and 5-year overall survival rates were 89%, 89%, 81%, and 50%, respectively. After 3 months of PEA, all patients had improvements in FC, 6MWD (from 326 ± 62 to 420 ± 63 m), B-type natriuretic peptide level (from 602 ± 599 to 268 ± 565 pg/mL), and systolic pulmonary artery pressure (from 79 ± 19 to 48 ± 19 mmHg). The patients with proximal disease (Jamieson type 1 or 2) had better survival than those with distal disease (Jamieson type 3 or 4), but there was no significant difference in mortality between FC III and IV. All of the four patients who did not undergo PEA survived for more than 3 years. CONCLUSIONS: Significant improvements in symptoms, functional capacity, and hemodynamics were achieved in the CTEPH patients after PEA. However, the overall survival was still unsatisfactory.

Cathepsin S promotes the development of pulmonary arterial hypertension.

Cysteine cathepsin proteases play critical roles in cardiovascular disease progression and are implicated in extracellular matrix (ECM) degradation. Patients with pulmonary arterial hypertension (PAH) exhibit increased elastase production by pulmonary arterial smooth muscle cells (PASMCs), which is related to the degradation of elastic fibers and pulmonary vascular remodeling. However, the mechanism by which cathepsins regulate the ECM and PASMC proliferation in PAH remains unclear. We hypothesized that cathepsin proteases in PASMCs promote the development of PAH. Here, we show overexpression of cathepsin S (Cat S) and degradation of elastic laminae in the lungs of patients with idiopathic PAH and in the PASMCs of monocrotaline-induced PAH model (MCT-PAH) rats. In addition, pulmonary hypertension can be treated in MCT-PAH rats by administering a selective Cat S inhibitor, Millipore-219393, which stimulates peroxisome proliferator-activated receptor-γ (PPARγ) to inhibit the expression of Cat S, thus suppressing the proliferation and migration of MCT-PAH PASMCs. We then reduced Cat S or PPARγ expression by using small interfering RNA in human PASMCs to demonstrate a mechanistic link between Cat S signaling and PPARγ protein, and the results suggest that PPARγ is upstream of Cat S signaling. In conclusion, the activity of Cat S in pulmonary vascular remodeling and degradation of elastin fibers through the disruption of PPARγ is pathophysiologically significant in PAH.

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.

Successful multidisciplinary treatment of uterine serous carcinoma in a patient who had previously undergone renal transplantation.

OBJECTIVE: Renal transplantation is a risk factor for premalignant and malignant changes of the endometrium. Thus, prompt and aggressive treatment of postoperative complications remains a major issue. We report the case of an asymptomatic postmenopausal woman with a history of renal transplantation who underwent surgery for uterine serous carcinoma (USC). CASE REPORT: An asymptomatic 59-year-old woman who had undergone renal transplantation presented with elevated serum CA-125 levels. Cancer screening revealed uterine serous carcinoma, for which she underwent total hysterectomy and bilateral salpingo-oophorectomy. Unfortunately, the postoperative course was complicated by cardiogenic shock and decompensated heart failure. The complexities of the cardiac problems and renal transplantation required a multidisciplinary approach involving different specialists. She was successfully discharged 48 days after the surgery. CONCLUSION: Gynecologic cancer screening in asymptomatic postmenopausal women after renal transplantation is warranted. If postoperative complications occur in this population, a multidisciplinary approach is recommended.

Factors associated with undiagnosed obstructive sleep apnoea among hypertensive patients: A multisite cross-sectional survey study in Taiwan.

AIMS AND OBJECTIVES: To investigate the distribution and risk factors associated with undiagnosed obstructive sleep apnoea among hypertensive patients. BACKGROUND: Obstructive sleep Apnoea has been deemed a cardinal risk factor affecting cardiovascular event, and the condition is still frequently overlooked clinically. The lack of advanced diagnosis often causes hypertensive patients with obstructive sleep apnoea to miss opportunities for preventing chronic diseases. DESIGN: A cross-sectional design. METHODS: A total of 215 hypertensive participants were recruited from the cardiovascular outpatients of medical centre in northern and middle Taiwan. The Chinese version of Pittsburgh Sleep Quality Index, the Chinese version of the Epworth Sleep Scale and a portable sleep monitoring device were used for data collection. Logistic regression analysis was conducted to identify the factors affecting hypertensive patients with obstructive sleep apnoea, and a multinomial logistic regression analysis was used to examine the major influence factors for each obstructive sleep apnoea severity level. RESULTS: 81.9% of the hypertensive participants were found having obstructive sleep apnoea. Concerning to the obstructive sleep apnoea severity, 50.0% of participants had mild obstructive sleep apnoea. After controlling the confounding variables, the supine position (odds ratio, 1.04; 95% CI, 1.01-1.07), SO2 (odds ratio, 0.58; 95% CI, 0.38-0.89) and oxygen desaturation index (odds ratio, 2.70; 95% CI, 1.18-6.18) were significantly associated with obstructive sleep apnoea. Furthermore, severe obstructive sleep apnoea was significantly correlated with gender (odds ratio, 0.04; 95% CI, 0.00-0.66), excessive daytime sleepiness (odds ratio, 20.27; 95% CI, 1.58-26.97) and oxygen desaturation index (odds ratio, 4.05; 95% CI, 1.86-8.81). CONCLUSIONS: Nearly 82% of the hypertensive participants were found having undiagnosed obstructive sleep apnoea, and 80% of them were mild or moderate severity. Oxygen desaturation index, SO2 and the supine position were found to be major predictors for obstructive sleep apnoea. Remarkably, oxygen desaturation index was the most significant predictor for mild, moderate and severe obstructive sleep apnoea. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers should enhance their sensitivities to hypertensive patients at a high risk for obstructive sleep apnoea by actively assessing common obstructive sleep apnoea symptoms and providing strategies to alleviate obstructive sleep apnoea symptoms.

Prostanoid EP4 agonist L-902,688 activates PPARγ and attenuates pulmonary arterial hypertension.

Prostacyclin agonists that bind the prostacyclin receptor (IP) to stimulate cAMP synthesis are effective vasodilators for the treatment of idiopathic pulmonary arterial hypertension (IPAH), but this signaling may occur through nuclear peroxisome proliferator-activated receptor-γ (PPARγ). There is evidence of scant IP and PPARγ expression but stable prostanoid EP4 receptor (EP4) expression in IPAH patients. Both IP and EP4 functionally couple with stimulatory G protein (Gs), which activates signal transduction. We investigated the effect of an EP4-specific agonist on pulmonary arterial remodeling and its regulatory mechanisms in pulmonary arterial smooth muscle cells (PASMCs). Immunoblotting evealed IP, EP4, and PPARγ expression in human pulmonary arterial hypertension (PAH) and monocrotaline (MCT)-induced PAH rat lung tissue. Isolated PASMCs from MCT-induced PAH rats (MCT-PASMCs) were treated with L-902,688, a selective EP4 agonist, to investigate the anti-vascular remodeling effect. Scant expression of IP and PPARγ but stable expression of EP4 was observed in IPAH patient lung tissues and MCT-PASMCs. L-902,688 inhibited IP-insufficient MCT-PASMC proliferation and migration by activating PPARγ in a time- and dose-dependent manner, but these effects were reversed by AH-23848 (an EP4 antagonist) and H-89 [a protein kinase A (PKA) inhibitor], highlighting the crucial role of PPARγ in the activity of this EP4 agonist. L-902,688 attenuated pulmonary arterial remodeling in hypoxic PAH mice and MCT-induced PAH rats; therefore, we conclude that the selective EP4 agonist L-902,688 reverses vascular remodeling by activating PPARγ. This study identified a novel EP4-PKA-PPARγ pathway, and we propose EP4 as a potential therapeutic target for PAH.

Peripheral Vascular Endothelial Dysfunction in Central Serous Chorioretinopathy.

Purpose: To explore the pathophysiology of central serous chorioretinopathy (CSC) by comparing peripheral vascular endothelium function in patients with CSC and control subjects. Methods: This study included 34 patients with CSC who attended the Department of Ophthalmology and 34 healthy age- and sex-matched healthy control subjects from a routine physical check-up population. Endothelium-dependent flow-mediated vasodilation (FMD) and endothelium-independent nitroglycerine-mediated vasodilation (NMD) were measured using high-resolution, two-dimensional ultrasonographic imaging of the brachial artery. Blood samples were taken to test serum glucose, cholesterol, triglyceride, alanine aminotransferase, uric acid, and high-sensitivity C-reactive protein (hs-CRP) levels. Results: The mean age of patients with CSC was 44.0 years (SD ±8.1) and that of controls 46.1 years (±9.9) (P = 0.352). There were no significant differences between groups in serum biochemical data, including serum glucose, alanine aminotransferase, uric acid, cholesterol, triglyceride, and hs-CRP. FMD was significantly impaired in patients with CSC compared with control subjects (CSC: 4.62 ± 1.96, control: 7.52 ± 2.63, P < 0.001), whereas NMD did not differ significantly between the two groups (CSC: 16.31 ± 5.60, control: 16.22 ± 5.56, P = 0.950). Conclusions: This study demonstrated impaired FMD in patients with CSC and the results have provided evidence of peripheral endothelium dysfunction associated with CSC in patients.

Long-Term Survival of Patients with Pulmonary Arterial Hypertension at a Single Center in Taiwan.

BACKGROUND: Clinical studies have suggested predictive parameters in mortality risk assessment for pulmonary arterial hypertension (PAH) patients. However, these studies predominantly include Caucasian population; information in Asian population is relatively deficient. In this study, we investigated the long-term survival of PAH patients and the predictors of mortality in our population. METHODS: We prospectively collected 70 patients with PAH at the Chang Gung Memorial Hospital between March 2002 and February 2015. Baseline data including functional class (FC), 6-minute walk distance (6MWD), hematological and biochemical data, echocardiography and cardiac catheterization were obtained before commencing PAH- targeted treatment. The follow-up period for analyses of survivors ended in October 2015. RESULTS: The mean age at diagnosis was 40.7 ± 15.2 years. Mean follow-up period was 4.6 ± 3.4 years, with 1-, 2-, 3-, and 5-year survival rates of 93%, 88%, 84%, and 77%, respectively. The baseline FC was worse in non-survivors than in survivors. More frequent presence of pericardial effusion, higher serum glucose levels, higher estimated systolic pulmonary artery pressure (SPAP) by echocardiography, and higher right atrial pressure (RAP) were found in non-survivors. Higher FC, lower 6MWD, and presence of pericardial effusion were associated with risk of mortality. Patients with worsening FC and increased serum uric acid had an increased risk of mortality during follow-up. CONCLUSIONS: The overall survival remained unsatisfactory in PAH patients. Baseline FC, 6MWD, pericardial effusion, RAP, and a worsening FC and an increased serum uric acid levels during follow-up were significant prognostic parameters.

Left bundle-branch block contraction patterns identified from radial-strain analysis predicts outcomes following cardiac resynchronization therapy.

A left bundle-branch block (LBBB) contraction pattern identified from longitudinal-strain analysis predicts outcomes following cardiac resynchronization therapy (CRT). We investigated the use of an LBBB-contraction pattern identified from radial- or circumferential-strain analysis in the prediction of CRT benefits. Eighty CRT candidates were prospectively enrolled. Before CRT implantation, speckle-tracking analyses in three deformation directions were performed to determine whether an LBBB-contraction pattern was present. The study endpoints were reverse remodeling at 6 months, and adverse outcomes including death or heart failure hospitalization. At 6 months, 49 (61%) patients had reverse remodeling. An LBBB-contraction pattern identified from the radial strain in the mid-ventricular short-axis view or longitudinal strain in the four-chamber view provided excellent true-positive (86%) and false-negative (8%) rates for predicting reverse remodeling. During a median follow-up of 30 months, 31 patients (39%) had adverse outcomes. Absence of an LBBB-contraction pattern in radial (hazard ratio 3.74; 95% confidence interval 1.83-7.62) or longitudinal strain (hazard ratio 3.49; 95% confidence interval 1.71-7.13) was significantly associated with an increased risk of adverse outcomes. Adding the LBBB-pattern assessment by radial-(model χ2 from 8.2 to 18.5, p = 0.005), or longitudinal-strain analysis (model χ2 from 8.2 to 16.9, p = 0.011) to a risk model significantly improved the model, including QRS duration and ischemic etiology. In conclusion, an LBBB-contraction pattern identified from radial-strain analysis in the mid-ventricular short-axis view predicted reverse remodeling and outcome following CRT, similarly to the longitudinal-strain analysis.

Simple obstructive sleep apnea patients without hypertension or diabetes accelerate kidney dysfunction: a population follow-up cohort study from Taiwan.

BACKGROUNDS: Obstructive sleep apnea (OSA) is common in patients on hemodialysis, but its correlation with chronic kidney disease (CKD) is not clear. We aimed to clarify the relationship between OSA without hypertension or diabetes and incidence of CKD in Taiwan. METHODS: This population-based cohort study consisted of patients with newly diagnosed OSA between 2000 and 2009. The comparison cohort was matched for age, sex, diabetes mellitus, and hypertension. All subjects previously diagnosed with acute or chronic kidney disease were excluded. The primary end point was newly diagnosed CKD. RESULTS: We identified 6866 subjects with OSA during the 10-year study period. The median duration until development of CKD in the OSA cohort was 3.2 years, 2.5 months earlier than that in the non-OSA cohort. After exclusion of hypertension and diabetes, 4319 OSA patients was identified and the hazard ratio (HR) of CKD with OSA was 1.37 (95 % confidence interval [CI], 1.05-1.77; p = 0.019). In the subgroup analysis, an increased incidence of CKD in OSA was observed in women (HR, 1.41; 95 % CI, 1.12-1.78; p = 0.0036). CONCLUSIONS: This longitudinal population-based cohort study provides evidence that patients with OSA even without diabetes or hypertension are at higher risk of developing CKD over the next 3 years and nearly 2.5 months earlier than the non-OSA cohort, particularly women.

Combined Global Longitudinal Strain and Intraventricular Mechanical Dyssynchrony Predicts Long-Term Outcome in Patients With Systolic Heart Failure.

BACKGROUND: Left ventricular (LV) ejection fraction (EF) and QRS duration enable prediction of outcome in patients with systolic heart failure (SHF). We assessed the predictive value of global longitudinal strain (GLS) and mechanical dyssynchrony for prognosis in SHF patients. METHODS AND RESULTS: Two-hundred and forty SHF patients with LVEF ≤40% were studied. Global LV function and intraventricular mechanical dyssynchrony were calculated as GLS and SD of the time to peak longitudinal strain (SDε) over 18 LV segments. The added value of GLS and SDε for outcome prediction was assessed using nested Cox models. Sixty-six patients (28%) reached the study endpoint of all-cause mortality/heart transplantation over a median follow-up period of 45 months. Baseline variables associated with adverse outcome were age, glomerular filtration rate, pulmonary artery systolic pressure, diabetes and LV end-systolic volume (model χ(2)=69.8). The predictive power of the clinical variables was greater with addition of GLS (χ(2)=81.1) or SDε (χ(2)=102.3) than with LVEF (χ(2)=73.9) or QRS duration (χ(2)=75.5; both P<0.005). GLS (HR, 1.88; P=0.03) and SDε (HR, 1.48; P=0.04) were independent predictors after adjustment for the baseline variables. Patients with impaired GLS (≥-7.8%) and mechanical dyssynchrony (SDε ≥72 ms) had poor outcome. CONCLUSIONS: Combined assessment of global LV function and mechanical dyssynchrony using speckle-tracking strain enabled the prediction of long-term outcome in SHF patients.