Access Site Complication Rates Following Peripheral Artery Revascularization in patients With End-Stage Renal Disease: A Comparison of Vascular Closure Devices and Manual Compression.

OBJECTIVES: Manual compression (MC) or vascular closure devices (VCDs) are used to achieve hemostasis after percutaneous transluminal angioplasty (PTA). However, limited data on the comparative safety and effectiveness of VCDs vs MC in patients with end-stage renal disease (ESRD) undergoing PTA are available. Accordingly, this study compared the safety and effectiveness of VCD and MC in patients with ESRD undergoing PTA. METHODS: This single-center retrospective cohort study included the data of patients with ESRD undergoing peripheral intervention at Chang Gung Memorial Hospital, Taiwan, from January 1, 2019, to June 30, 2022. The patients were divided into VCD and MC groups. The primary endpoint was a composite of puncture site complications, including acute limb ischemia, marked hematoma, pseudoaneurysm, and puncture site bleeding requiring blood transfusion. RESULTS: We included 264 patients with ESRD undergoing PTA, of whom 60 received a VCD and 204 received MC. The incidence of puncture site complications was 3.3% in the VCD group and 4.4% in the MC group (hazard ratio: .75; 95% confidence interval: .16-3.56 L P = 1.000), indicating no significant between-group difference. CONCLUSION: VCDs and MC had comparable safety and effectiveness for hemostasis in patients with ESRD undergoing peripheral intervention.

Cancer Therapy-Related Cardiac Dysfunction in Patients With Prostate Cancer Undergoing Androgen Deprivation Therapy.

Background The risk of cardiac dysfunction for patients with prostate cancer undergoing androgen deprivation therapy (ADT) in the real-world setting remains unclear. Methods and Results A total of 1120 patients with prostate cancer and a baseline echocardiography scan were identified from Chang Gung Research Database between January 1, 2001 and December 31, 2019. Patients were treated with gonadotropin-releasing hormone agonist therapy, gonadotropin-releasing hormone antagonist therapy, or bilateral orchiectomy. Changes in left ventricular ejection fraction (LVEF) were further assessed in 421 patients using repeated measurements of LVEF before and during ADT treatment. The incidence of cancer therapy-related cardiac dysfunction (CT-RCD) was evaluated and defined as a ≥10% absolute decline in LVEF from baseline to a value of <53%. Among 421 patients undergoing ADT, LVEF declined from 66.3±11.3% to 62.5±13.6% (95% CI of mean difference: -5.0% to -2.7%) after a mean follow-up period of 1.6±0.8 years. CT-RCD occurred in 58 patients (13.7%) with a nadir LVEF of 40.3±9.1% after ADT. Lower baseline LVEF was significantly associated with CT-RCD (odds ratio, 1.07 [95% CI, 1.04-1.10]). The area under the curve of baseline LVEF for discriminating CT-RCD was 75.6%, with the corresponding optimal cutoff value of 64.5% (sensitivity, 79.3%; specificity, 67.2%). Conclusions ADT with gonadotropin-releasing hormone agonist therapy, gonadotropin-releasing hormone antagonist therapy, and bilateral orchiectomy were associated with an increased risk of CT-RCD in patients with prostate cancer. In addition, lower baseline LVEF was a significant predictor of CT-RCD in patients with prostate cancer undergoing treatment with ADT.

The cardiovascular and renal effects of glucagon-like peptide 1 receptor agonists in patients with advanced diabetic kidney disease.

BACKGROUND: To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) have cardiovascular and renal protective effects in patients with advanced diabetic kidney disease (DKD) with an estimated glomerular filtration rate (eGFR) < 30 mL/min per 1.73 m2. METHODS: In this cohort study, patients with type 2 diabetes mellitus and eGFR < 30 mL/min per 1.73 m2 with a first prescription for GLP-1RAs or dipeptidyl peptidase 4 inhibitors (DPP-4is) from 2012 to 2021 (n = 125,392) were enrolled. A Cox proportional hazard model was used to assess the cardiorenal protective effects between the GLP-1RA and DDP-4i groups. RESULTS: A total of 8922 participants [mean (SD) age 68.4 (11.5) years; 4516 (50.6%) males; GLP-1RAs, n = 759; DPP-4is, n = 8163] were eligible for this study. During a mean follow-up of 2.1 years, 78 (13%) and 204 (13.8%) patients developed composite cardiovascular events in the GLP-1RA and DPP-4i groups, respectively [hazard ratio (HR) 0.88, 95% confidence interval CI 0.68-1.13]. Composite kidney events were reported in 134 (38.2%) and 393 (44.2%) patients in the GLP-1RA and DPP-4i groups, respectively (subdistribution HR 0.72, 95% CI 0.56-0.93). CONCLUSIONS: GLP-1RAs had a neutral effect on the composite cardiovascular outcomes but reduced composite kidney events in the patients with advanced DKD compared with DPP-4is.

Deficiency of circadian gene cryptochromes in bone marrow-derived cells protects against atherosclerosis in LDLR-/- mice.

Cryptochromes are photoreceptors that mediate the circadian entrainment by light in plants and animals. They are also involved in magnetic field sensing in some animals. Recent studies suggest that cryptochromes play an essential role in metabolism and cardiovascular disease. However, the tissue-specific function of cryptochromes in atherosclerosis is unknown. We transplanted bone marrow from wild-type (WT) and cryptochrome 1/2 knockout (Cry1/2 KO) mice into irradiated recipient low-density lipoprotein receptor knockout (LDLR-/- ) mice and induced atherosclerosis with a high cholesterol diet for 12 weeks. There was a reduction in atherosclerotic plaques and macrophage accumulation in the aorta of LDLR-/- mice that received Cry1/2 KO bone marrow compared to mice that received WT bone marrow. Bone marrow-derived macrophages (BMDMs) from Cry1/2 KO mice exhibited impaired uptake of low-density lipoprotein, and subsequently, impaired foam cell formation. Analysis of macrophage mRNA circadian oscillations revealed that the circadian rhythm of the LDLR mRNAs was lost in Cry1/2 KO BMDMs. Reinstalling the circadian oscillatory LDLR mRNAs using adenovirus into the BMDMs was able to rescue the lipid uptake and foam cell formation function. However, the noncircadian oscillatory LDLR mRNAs exhibited reduced ability to rescue the macrophage functions. These findings indicate that cryptochromes in bone marrow-derived cells are critical mediators of atherosclerosis through regulation of the LDLR mRNA circadian rhythm. Therapeutic measures targeting cryptochromes in the macrophage may have important implications for atherosclerosis.

Biologic Agents Reduce Cardiovascular Events in Rheumatoid Arthritis Not Responsive to Tumour Necrosis Factor Inhibitors: A National Cohort Study.

BACKGROUND: Tumour necrosis factor inhibitors (TNFis) improve joints outcomes and reduce cardiovascular (CV) risk in patients with rheumatoid arthritis (RA). However, 20%-45% of RA patients are TNFi poor responders and have a significantly higher risk of CV events. In these TNFi nonresponders, the use of second-line biologic agents to improve synovial outcomes is supported by clinical trials and real-world experience. However, it remains unknown what kind of immune-mediated agent has the best CV prevention effect in this high-risk population. METHODS: A nationwide RA cohort obtained from Taiwan's National Health Insurance claims database was constructed. RA patients first treated with TNFis who then received either rituximab, tocilizumab, or abatacept were enrolled and followed for 2 years. RESULTS: A total of 89,973 RA patients were screened and 1,584 patients ultimately included. The incidences of major adverse cardiac events (MACE) at 2 years in the rituximab, tocilizumab, and abatacept groups were 7.17%, 2.75% and 2.38%, respectively. Multivariate adjusted Cox analysis showed that tocilizumab had significantly lower risk than rituximab in myocardial infarction (hazard ratio [HR] 0.12, 95% confidence interval [CI] 0.02-0.56; P = 0.008), and MACE (HR 0.41, 95% CI 0.23-0.72; P = 0.002). In addition, abatacept also had significant lower adjusted risk than rituximab in stroke (HR 0.18, 95% CI 0.05-0.64; P = 0.008), heart failure (HR 0.20, 95% CI 0.05-0.83; P = 0.027), and MACE (HR 0.25, 95% CI 0.11-0.55; P < 0.001) in multivariate analysis. CONCLUSIONS: TNFi-nonresponder patients with RA who received second-line tocilizumab or abatacept had more benefit on CV events prevention compared with those who received rituximab.

FTO variants are associated with ANGPTL4 abundances and correlated with body weight reduction after bariatric surgery.

BACKGROUND: The FTO (fat mass- and obesity-associated) gene variant is an established obesity-susceptibility locus. FTO protein is a nucleic acid demethylase and FTO genetic variants form long-range functional connections with IRX3, which regulates fat mass and metabolism in humans. From our previous results, we found FTO regulates the metabolism of triglyceride in adipocytes through demethylating Angptl4 (angiopoietin-like protein 4) mRNA in mice. We hypothesized that the FTO genetic variants regulate ANGPTL4 abundances in human adipose tissues and affect the outcome after bariatric surgery. METHODS AND RESULTS: We recruited 188 obesity subjects with body mass indices (BMI)>35kg/m2 and 102 non-obese subjects with BMI<30kg/m2 from the OCEAN registry between 2011 and 2014. The distribution of FTO variants rs9939609 among participates was 73.79% TT, 23.79% AT, and 2.41% AA. The subjects with FTO variants AA or AT were correlated with higher BMI than those with FTO variants TT. The serum ANGPTL4 levels were significantly higher in obese subjects and positively correlated with the presence of FTO AA or AT haplotype. Of these participates, 84 obese subjects underwent bariatric surgery and adipose Angptl4 expressions were analyzed. The adipose Angptl4 mRNA levels and protein abundances were correlated with FTO AA or AT haplotype. The magnitude of excess body weight reduction 2 years after bariatric surgery was correlated with the adipose ANGPTL4 protein levels. CONCLUSION: Adipose ANGPTL4 abundances were affected by the presence of FTO obesity risk haplotype and correlated with excess weight loss percentage after bariatric surgery. These data signify the critical role of FTO variants and adipose ANGPTL4 in fatty acid metabolism and bariatric outcomes in humans.

Regulation of autophagy in leukocytes through RNA N6-adenosine methylation in chronic kidney disease patients.

Patients with chronic kidney diseases have multiple cellular dysfunctions leading to increased atherosclerosis, impaired immunity, and disturbed metabolism. However, it is unclear what is the fundamental signaling served as a marker or as a mediator for the dysregulated function in their leukocytes or tissues. Here we hypothesized that the N6-Methyladenosine (m6A) modification of the RNA in the leukocytes is responsible for the cellular dysfunction in chronic kidney diseases. Patients with chronic kidney diseases had significantly less m6A abundances in leukocytes and elevated RNA demethylase FTO proteins. The uremic toxin, indoxyl sulfate, activated the autophagy flux through modulation of FTO and m6A modifications in RNA. Notably, knockdown of FTO or inhibit the m6A by 3-deazaadenosine blocks the effects of indoxyl sulfate on autophagy activation in cells. These findings provide new insights into the mechanisms underlying chronic kidney disease-associated cellular dysfunction. Targeting RNA m6A modification may be a novel strategy for the treatment of chronic kidney diseases and autophagy.

2019 Focused Update of the Guidelines of the Taiwan Society of Cardiology for the Diagnosis and Treatment of Heart Failure.

Heart failure is a growing epidemic, especially in Taiwan because of the aging population. The 2016 Taiwan Society of Cardiology - Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry showed that the guideline-recommended therapies were prescribed suboptimally both at the time of hospital discharge and during follow-up. We, therefore, conducted this 2019 focused update of the guidelines of the Taiwan Society of Cardiology for the diagnosis and treatment of heart failure to reinforce the importance of new diagnostic and therapeutic modalities of heart failure. The 2019 focused update discusses new diagnostic criteria, pharmacotherapy, non-pharmacological management, and certain co-morbidities of heart failure. Angiotensin receptor neprilysin inhibitor and If channel inhibitor is introduced as new and recommended medical therapies. Latest criteria of cardiac resynchronization therapy, implantable cardioverter-defibrillator, heart transplantation, and ventricular assist device therapy are reviewed in the non-pharmacological management chapter. Co-morbidities in heart failure are discussed including chronic kidney disease, diabetes, chronic obstructive pulmonary disease, and sleep-disordered breathing. We also explain the adequate use of oxygen therapy and non-invasive ventilation in heart failure management. A particular chapter for chemotherapy-induced cardiac toxicity is incorporated in the focused update to emphasize the importance of its recognition and management. Lastly, implications from the TSOC-HFrEF registry and post-acute care of heart failure are discussed to highlight the importance of guideline-directed medical therapy and the benefits of multidisciplinary disease management programs. With guideline recommendations, we hope that the management of heart failure can be improved in our society.

Excessive irisin increases oxidative stress and apoptosis in murine heart.

Irisin is an exercise-related myokine. The abundance of irisin is associated with many diseases, such as myocardial infarction, chronic kidney disease, metabolic syndrome, obesity, and diabetes mellitus. In cardiomyocytes, irisin modulates the mitochondrial thermogenesis, regulates ischemic responses, and affects calcium signaling. Previous studies suggested that irisin increases cardiomyoblast mitochondrial functions and protects ischemic and reperfusion injury in ex vivo murine heart. In human, clinical studies have shown that acute myocardial infarction patients with more elevated serum irisin abundances are associated with increased major adverse cardiovascular events. However, the mechanisms responsible for this discrepancy between in myocardial infarction patients and ex vivo murine heart is unclear. Based on the clinical observations, we hypothesized that excessive irisin might lead to mitochondrial dysfunctions and cardiomyocyte damages. Our data showed that overexpression of irisin in mice with the adenovirus resulted in enhanced mitochondrial respiration with a higher oxygen consumption rate. Enhanced irisin expression in heart and irisin treatment in cardiomyocytes increased reactive oxygen species production. Furthermore, irisin treatment in cardiomyocytes enhanced the apoptosis and the cleaved caspase 9 levels in hypoxic condition. Pathway analysis in the murine heart with the overexpression of irisin showed that angiopoietin-Tie2, IL-8, IL-13, TGF-ß, and thrombopoietin signaling were affected by irisin. Collectively, these results supported that excessive irisin causes mitochondrial overdrive with a higher reactive oxygen species production, which results in increased apoptosis of cardiomyocytes in a hypoxic environment.

Impact of Homocysteine Level on Long-term Cardiovascular Outcomes in Patients after Coronary Artery Stenting.

AIM: The prognostic value of homocysteine (HCY) in patients with coronary artery diseases (CAD) is still controversial. The objective of this study was to investigate whether elevated HCY level at admission predict long-term outcomes in patients after percutaneous coronary interventions (PCI) with coronary artery stenting. METHODS: From the institutional registry of Cardiovascular Atherosclerosis and Percutaneous TrAnsluminal INterventions (CAPTAIN), we enrolled a total of 1,307 patients with documented CAD undergone PCI with bare metal stents from July 2003 to December 2014. They were divided into two groups according to the fasting plasma HCY levels before catheterization: group Ⅰ (883 patients, ＜12 µmol/L) and group II (424 patients, ≥12 µmol/L). The primary endpoint was occurrence of major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, stroke, target lesion revascularization, new lesion stenting, and requiring bypass surgery. RESULTS: After a mean follow-up period of 58±41 months, the group II patients had a higher MACE rate (33.3% vs. 25.6%, p=0.005). The main differences between two groups were cardiac death (8.0% vs. 3.4%, p=0.001) and new lesion stenting (13.6% vs. 9.5%, p=0.034). The risks of long-term MACE remained significantly higher in patients with elevated HCY level (≥12 µmol/L) after adjusting for clinical variables, with a hazard ratio of 1.29 (95% CI, 1.02-1.64, p=0.036). CONCLUSIONS: Elevated HCY level (≥12 µmol/L) was independently associated with increased risk of long-term cardiovascular events in patients after coronary artery bare metal stents implantations. Thus, hyperhomocysteinemia may remain a useful prognostic marker for the risk assessment in clinical care of CAD patients.

Prognostic Impact of 9-Month High-Sensitivity C-Reactive Protein Levels on Long-Term Clinical Outcomes and In-Stent Restenosis in Patients at 9 Months after Drug-Eluting Stent Implantation.

INTRODUCTION: The level of 9-month high-sensitivity C-reactive protein (hsCRP) in predicting cardiovascular outcomes is scanty in patients at 9 months after receiving drug-eluting stent (DES) implantations. This study aims to evaluate the relationship between 9-month follow-up hsCRP levels and long-term clinical outcomes in patients at 9 months after receiving DES. METHODS: A total of 1,763 patients who received 9-month follow-up angiography were enrolled and grouped according to hsCRP level 9 months after the DES implantation: group I (718 patients, hsCRP<1.0 mg/L), group II (639 patients, 1.0 ≦ hsCRP ≦ 3.0 mg/L), and group III (406 patients, hsCRP>3.0 mg/L). RESULTS: Group III patients had a lower cardiovascular event-free survival rate than group I or II patients during a follow-up of 64 ± 45 months (64.5% vs. 71.6% vs. 72.8%, respectively, p = 0.012). Multivariate analysis showed that a follow-up hsCRP level <3.0 mg/L was an independent predictor of a major adverse cardiovascular event (cardiac death, reinfarction, target lesion revascularization, stenting in a new lesion, or coronary bypass surgery). Group III patients had a higher restenosis rate (11.3% vs. 5.8% vs. 6.6%, respectively, p = 0.002) and loss index (0.21 ± 0.32 vs. 0.16 ± 0.24 vs. 0.18 ± 0.28, respectively, p = 0.001) than group I or II patients in 9-month follow-up angiography. CONCLUSIONS: A high 9-month follow-up hsCRP level is an independent predictor of long-term clinical cardiovascular outcomes in patients at 9 months after DES implantation. It is also associated with a higher restenosis rate, larger late loss and loss index at 9 months after DES implantation.

Short- and long-term major cardiovascular adverse events in carotid artery interventions: a nationwide population-based cohort study in Taiwan.

INTRODUCTION: Carotid artery stenosis is one of the leading causes of ischemic stroke. Carotid artery stenting has become well-established as an effective treatment option for carotid artery stenosis. For this study, we aimed to determine the efficacy and safety of carotid stenting in a population-based large cohort of patients by analyzing the Taiwan National Healthcare Insurance (NHI) database. METHODS: 2,849 patients who received carotid artery stents in the NHI database from 2004 to 2010 were identified. We analyzed the risk factors of outcomes including major adverse cardiovascular events including death, acute myocardial infarction, and cerebral vascular accidents at 30 days, 1 year, and overall period and further evaluated cause of death after carotid artery stenting. RESULTS: The periprocedural stroke rate was 2.7% and the recurrent stroke rate for the overall follow-up period was 20.3%. Male, diabetes mellitus, and heart failure were significant risk factors for overall recurrent stroke (Hazard Ratio (HR) = 1.35, p = 0.006; HR = 1.23, p = 0.014; HR = 1.61, p < 0.001, respectively). The periprocedural acute myocardial infarction rate was 0.3%. Age and Diabetes mellitus were the significant factors to predict periprocedural myocardial infarction (HR = 3.06, p = 0.019; HR = 1.68, p < 0.001, respectively). Periprocedural and overall mortality rates were 1.9% and 17.3%, respectively. The most significant periprocedural mortality risk factor was acute renal failure. Age, diabetes mellitus, acute or chronic renal failure, heart failure, liver disease, and malignancy were factors correlated to the overall period mortality. CONCLUSION: Periprocedural acute renal failure significantly increased the mortality rate and the number of major adverse cardiovascular events, and the predict power persisted more than one year after the procedure. Age and diabetes mellitus were significant risk factors to predict acute myocardial infarction after carotid artery stenting.

Pericardiocentesis adverse event risk factors: a nationwide population-based cohort study.

OBJECTIVES: Echocardiography-guided pericardiocentesis has been the leading procedure for diagnosis and therapy of pericardial effusion. We aimed to identify risk factors for recurrence, complications, and mortality in pericardial effusion patients treated with pericardiocentesis. METHODS: We identified and collected data from 8,101 patients receiving pericardiocentesis between 1997 and 2010 from the Taiwan National Health Insurance Research Database. A multivariate regression model was used to investigate risk factors for recurrence, complications, and death. RESULTS: There were 8,565 admissions among 8,101 patients. The most common underlying condition was malignancy (41%), especially lung cancer (23%), tuberculosis (9.0%), and acute pericarditis (8.2%). Surgical drainage was required in 12.7% of cases. Recurrence was more likely in patients with malignancy (HR 2.20, p < 0.001), but complications were less likely (OR 0.52, p = 0.003). In-hospital death numbers and complication risks (OR 2.38, p < 0.001; OR 1.27, p = 0.01) were greater in the catheter-related cardiac procedure group than in the other groups. CONCLUSIONS: Malignant neoplasms and catheter-based cardiac procedures have become major risk factors for adverse events in patients receiving pericardiocentesis in Taiwan. Malignancy leads to an increase in recurrence and in-hospital mortality but is associated with a lower rate of acute complications. Cardiac catheterization procedures and surgery increase both complications and in-hospital mortality.