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The correlation between peak oxygen uptake and GWI as well as GCW was strongest in patients with ischemic cardiomyopathy (r = 0.56, p = 0.001 and r = 0.53, p = 0.001, respectively). The median follow-up was 16 months (IQR 12-18.5). Thirty one patients met the combined endpoint Four patients died, eight underwent transplantation, and 19 underwent implantation of a left ventricular assist device. In the multivariate Cox regression analysis, only NYHA class, NT-proBNP and GWI (hazard ratio [HR] for every 50 mmHg% 0.85; 95% CI 0.77-0.94; p = 0.002) as well as GCW (HR for every 50 mmHg% 0.86; 95% CI 0.79-0.94; p = 0.001) were identified as independent predictors of the endpoint. The cut-off value for predicting the outcome was 455 mmHg% for GWI (AUC 0.80; p less then 0.0001; sensitivity 77.4%; specificity 71.6%) and 530 mmHg% for GCW (AUC 0.80; p less then 0.0001; sensitivity 74.2%; specificity 78.4%). Conclusions GWI and GCW are powerful predictors of outcome in patients with advanced heart failure.Background Aging patients easily suffer from non-ST segment elevation myocardial infarction (NSTEMI). Our previous studies revealed declined function of endothelial progenitor cells (EPCs) in the elderly. However, the impact of aging on EPC function and severity in male NSTEMI patients and its possible mechanism is unclear until now. Methods We measured the circulating EPC function including migration, proliferation, and adhesion in aging or young male patients with NSTEMI. The GRACE and TIMI risk score were evaluated. Plasma levels of interleukin-6 (IL-6) and interleukin-17 (IL-17) were also detected in all patients. Results Compared with the young group, the old male patients with NSTEMI had higher GRACE score and TIMI score and decreased function of circulating EPCs. EPC function was negatively correlated with GRACE score and TIMI score. IL-6 and IL-17 level were higher in the old group than those in the young group. There was a significant negative correlation between EPC function and IL-6 or IL-17. Moreover, IL-6 and IL-17 positively correlated with GRACE and TIMI score. Age was positively related with GRACE or TIMI score and plasma level of IL-6 or IL-17, but inversely correlated with EPC function. Conclusions The current study firstly illustrates that the age-related decrement in EPC function is related to the severity of NSTEMI in male patients, which may be connected with systemic inflammation. These findings provide novel insights into the pathogenetic mechanism and intervention target of aging NSTEMI.The level of low-density lipoprotein cholesterol (LDL-C) decreases to a certain extent after daily meals; however, the influencing factor of this phenomenon has not been fully elucidated. This study included 447 patients with coronary heart disease (CHD). Serum levels of blood lipid parameters at 0, 2, and 4 hours (h) after a daily breakfast were monitored in all subjects. The levels of total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C) and non-HDL-C significantly decreased, while those of triglycerides (TG) and remnant cholesterol (RC) significantly increased from baseline to 4 h in both male and female patients (P less then 0.05). Multiple linear regression analysis showed that fasting LDL-C level, the non-fasting change in RC level at 4 h and fasting TG level were significant predictors of the non-fasting change in LDL-C level at 4 h in patients with CHD, and fasting LDL-C level was the most significantly associated with the non-fasting change in LDL-C level. Patients with lower levels of fasting LDL-C had smaller non-fasting changes in LDL-C levels. When the fasting LDL-C level was less then 1.4 mmol/L, both absolute reduction and percent reduction in LDL-C level at 4 h were almost zero, which means that the non-fasting LDL-C level at 4 h was approximately equivalent to its fasting value (P less then 0.05). This result indicated that the non-fasting changes in LDL-C levels were influenced by fasting LDL-C levels in patients with CHD. When the fasting LDL-C level was less then 1.4 mmol/L, the non-fasting LDL-C level could replace the fasting value to guide treatment.Background Coronary artery calcification (CAC) may provide insight to the patients' coronary artery disease (CAD) risks and influence early intervention. With increasing use of non-gated CT scans in clinical practice, the visual coronary artery scoring system (Weston Method) could quickly provide clinicians with important information of CAC for patient triage and management. Methods We retrospectively studied the available CT imaging data and estimated CAC burden using the Weston method in 493 emergency room or other hospitalized patients. The Weston scores were calculated by the sum of the score for each vessel including the left main, left anterior descending, left circumflex artery and right coronary artery (range 0-12). The primary endpoint was a composite of the major adverse cardiac events (MACEs), including cardiac death, myocardial infarction, stroke, and coronary revascularization. Results During a median follow-up of 85 months, a total of 25 (5.1%) MACE were recorded and 57 (11.2%) patients died from any causes. Detectable CAC was most common (96%) in the left anterior descending coronary arteries. Multivariable analysis showed that CAC total scores were independent predictors for MACE and all-cause mortality. Receiver operating characteristic analysis showed that CAC total score ≥5 was the optimal cutoff value for predicting MACEs. Conclusions In the emergency room and hospitalized patients, the semi-quantitation of CAC burden using the Weston score system was related to the long-term cardiovascular outcomes including mortality. Clinicians and radiologists should maximize the value of non-contrast chest CT images by reporting CAC details.Background Previously, we invented a therapeutic vaccine targeting the endothelin-A receptor (termed ETRQβ-002). ETRQβ-002 successfully prevented the remodeling of pulmonary arterioles (PAs) and right ventricle (RV) without significant immune-mediated damage in experimental pulmonary arterial hypertension (PAH) mice models. Objective Here, we aim to further evaluate the long-term effects of ETRQβ-002. Methods PAH mice model was induced by a combination of subcutaneous injection with Sugen5416 and chronic hypoxic conditions (10% O2). PAH mice were immunized with ETRQβ-002 at different time points, and the experiment lasted for 21 weeks. Hemodynamic, histological, and biochemical analyses were conducted to evaluate the long-term effects of ETRQβ-002. Results We demonstrated that the titer of the specific antibody against ETR-002 could be maintained chronically after periodic booster immunization in PAH mice. Long-term reduction of right ventricular systolic pressure and amelioration of PA remodeling by ETRQβ-002 were confirmed. Moreover, we found that ETRQβ-002 also exerted antiproliferation, anti-inflammation, and antifibrosis effects in PA remodeling. Besides, ETRQβ-002 durably limited pathological RV hypertrophy and fibrosis. Finally, no immune-mediated damage was observed in hepatic or renal function or by pathology in liver and kidney during the long-term administration of ETRQβ-002. Conclusion Our findings indicate that ETRQβ-002 provides long-term therapeutic effects in Sugen/hypoxia-induced PAH animals and offers a promising clinical prospect for PAH treatment.Background Heart failure (HF) is a multifactorial syndrome with pathophysiological complexities still not fully understood. Higher mean platelet volume (MPV), a potential marker of platelet activation, and high concentrations of parathyroid hormone (PTH) have been implicated in the pathogenesis of HF. Aim This study aims to investigate sex-specifically the association between PTH concentrations and platelet indices in phenotypes of HF. Methods and Results PTH and platelet indices (MPV and platelet count) were available in 1,896 participants from the MyoVasc study in Mainz, Germany. Multivariable linear regression models, adjusted for age, sex, season, vitamin D status, cardiovascular risk factors, comorbidities, estimated glomerular filtration rate, and medication, were used to assess the associations between platelet indices and PTH. The results showed distinct sex-specific associations between PTH and platelet indices. A positive association between PTH and MPV was found in females with symptomatic HF with reduced ejection fraction (HFrEF) only [β = 0.60 (0.19; 1.00)]. Platelet count was inversely associated with PTH in male HFrEF individuals [β = -7.6 (-15; -0.30)] and in both males and females with HF with preserved ejection fraction (HFpEF). Conclusion This study reports differential, sex-specific relationships between PTH and platelet indices in HF individuals independent of vitamin D status and clinical profile. Particularly in phenotypes of symptomatic HF, distinct associations were observed, suggesting a sex-specific mechanism involved in the interaction between PTH and platelets.Background Early repolarization syndrome (ERS) is an inherited sudden cardiac death (SCD) syndrome. The present study investigates the role of genetic variants in cardiac calcium-channel genes in the pathogenesis of ERS and probes the underlying mechanisms. find more Methods Polymerase chain reaction-based next-generation sequencing was carried out using a targeted gene approach. Unrelated ERS probands carrying calcium-channel variants were evaluated clinically and compared with matched healthy controls. Wild-type (WT) and mutant CACNA1C genes were coexpressed with CACNB2b and CACNA2D1 in HEK293 cells and studied using whole-cell patch-clamp techniques and confocal fluorescence microscope. Results Among 104 ERS probands, 16 carried pathogenic variants in calcium-channel genes (32.2 ± 14.6 years old, 87.5% male). The symptoms at diagnosis included syncope (56.3%), ventricular tachycardia/fibrillation (62.5%), and SCD (56.3%). Three cases (18.8%) had a family history of SCD or syncope. Eight patients (50.0%) had a singlerepolarization. In the case of CACNA1C-P817S, impaired trafficking of the channel to the membrane contributes to the LOF.Purpose The change in coronary physiology from lipid-lowering therapy (LLT) lacks an appropriate method of examination. Quantitative flow ratio (QFR) is a novel angiography-based approach allowing rapid assessment of coronary physiology. This study sought to determine the impact of low-density lipoprotein cholesterol (LDL-C) goal achievement on coronary physiology through QFR. Methods Cases involving percutaneous coronary intervention (PCI) and 1-year angiographic follow-up were screened and assessed by QFR analysis. Patients were divided into two groups according to the LDL-C level at the 1-year follow-up (1) goal-achievement group (LDL-C less then 1.8 mmol/L or reduction of ≥50%, n = 146, lesion = 165) and (2) non-achievement group (n = 286, lesion = 331). All QFR data and major adverse cardiovascular and cerebrovascular events (MACCEs) at 1 year were compared between groups. Results No differences between the groups in quantitative coronary angiography (QCA) data or QFR post-PCI were found. At the 1-year follow-up, lower percentage diameter stenosis (DS%) and percentage area stenosis (AS%) were recorded in the goal-achievement group (27.89 ± 10.16 vs. 30.93 ± 12.03, p = 0.010, 36.57 ± 16.12 vs. 41.68 ± 17.39, p = 0.003, respectively). Additionally, a better change in QFR was found in the goal-achievement group (0.003 ± 0.068 vs. -0.018 ± 0.086, p = 0.007), with a lower incidence of physiological restenosis and MACCEs (2.1 vs. 8.4%, p = 0.018, 5.4 vs. 12.6%, p = 0.021, respectively). Conclusion Evaluated by QFR, patients who achieved the LDL-C goal appear to have a better coronary physiological benefit. This group of patients also has a better clinical outcome.
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