Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants Compared with Vitamin K Antagonists in Patients with Atrial Fibrillation and Type 2 Valvular Heart Disease: A Systematic Review and Meta-Analysis.

PURPOSE: This meta-analysis aimed to evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and type 2 valvular heart disease (VHD). METHODS: We searched the PubMed, LILACS, and MEDLINE databases to retrieve, randomized controlled trials (RCTs) comparing NOACs and VKAs in patients with AF and type 2 VHD, excluding mitral stenosis (moderate to severe, of rheumatic origin) or mechanical heart valves. The efficacy outcomes assessed were stroke and systemic embolism (SE), while safety outcomes included major bleeding and intracranial hemorrhage (ICH). RESULTS: Seven RCTs, including 16,070 patients with AF and type 2 VHD, were included. NOACs reduced the risk of stroke/SE (relative risk [RR], 0.75; 95% confidence interval [CI], 0.64-0.89; P = 0.0005), with no significant difference in major bleeding (RR, 0.88; 95% CI, 0.64-1.21; P = 0.43). The risk of ICH was reduced with NOACs (RR, 0.46; 95% CI, 0.27-0.77; P = 0.003). For patients with AF and bioprosthetic heart valve (five trials, 2805 patients), stroke/SE risks (RR, 0.65, 95% CI, 0.44-0.96) with NOACs were superior to VKAs. Major bleeding risks without ENVISAGE TAVI AF trial (RR, 0.53; 95% CI, 0.30-0.94; P = 0.03) with NOACs were superior to VKAs. The risks of ICH (RR, 0.61; 95% CI 0.34-1.09; P = 0.09) with NOACs were comparable to VKAs. CONCLUSIONS: NOACs demonstrate efficacy and safety in patients with AF and type 2 VHD and reduce the risk of stroke/SE and ICH when compared with those with VKAs.

Pharmacological activation of estrogenic receptor G protein-coupled receptor 30 attenuates angiotensin II-induced atrial fibrosis in ovariectomized mice by modulating TGF-ß1/smad pathway.

BACKGROUND: G-protein-coupled ER (GPR30) plays an important role in cardioprotection. Recent studies have shown that the GPR30-specific agonist G-1 reduces the degree of myocardial fibrosis in rats with myocardial infarction, reduces the morbidity associated with atrial fibrillation, and inhibits the proliferation of cardiac fibroblasts in animal experiments. Nevertheless, the underlying mechanism of myocardial fibrosis and atrial fibrillation remains unclear. In this study, we explored the mechanism underlying the effect of GPR30 on atrial fibrosis and atrial fibrillation in OVX mice. METHODS: We established an animal model of atrial fibrillation induced by Ang II (derived from OVX C57BL/6 female mice) and observed the role of G-1 in cardiac function by echocardiography, hemodynamics, morphology and fibrosis-related and apoptosis-related protein expression by Masson's trichrome, immunofluorescence, western blotting and TUNEL staining. RESULTS: Echocardiography and body surface ECG showed that G-1 combined with Ang II significantly reduced atrial fibrosis and atrial fibrillation compared to Ang II alone. The G-1 treatment group exhibited changes in the mRNA and protein expression of apoptosis-related genes. Moreover, G-1 treatment also altered the levels of inflammation-related proteins and mRNAs. In primary cultured cardiac fibroblasts (CFSs), proliferation was significantly increased in response to Ang II, and G-1 inhibited cell proliferation and apoptosis. CONCLUSION: GPR30 is a potential therapeutic target for alleviating atrial fibrosis in OVX mice by upregulating Smad7 expression to inhibit the TGF-ß/Smad pathway.

Effect of Corticosteroid on Renal Water and Sodium Excretion in Symptomatic Heart Failure: Prednisone for Renal Function Improvement Evaluation Study.

BACKGROUND: Recent evidence indicates that prednisone can potentiate renal responsiveness to diuretics in heart failure (HF). However, the optimal dose of prednisone is not known. METHOD: Thirty-eight patients with symptomatic HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/d, n = 8), medium-dose (30 mg/d, n = 10), or high-dose prednisone (60 mg/d, n = 10), for 10 days. During this time, we recorded the 24-hour urinary output and the 24-hour urinary sodium excretion, at baseline, on day 5 and day 10. We also monitored the change in the concentration of serum creatinine, angiotensin II, aldosterone, high-sensitive C-reactive protein, tumor necrosis factor-α, interleukin 1ß, and interleukin 6. RESULTS: Low-dose prednisone significantly enhanced urine output. However, the effects of medium- and high-dose prednisone on urine output were less obvious. As for renal sodium excretion, high-dose prednisone induced a more potent natriuresis than low-dose prednisone. Despite the potent diuresis and natriuresis induced by prednisone, serum creatinine, angiotensin II, and aldosterone levels were not elevated. These favorable effects were not associated with an inflammatory suppression by glucocorticoids. CONCLUSIONS: Only low-dose prednisone significantly enhanced urine output. However, high-dose prednisone induced a more potent renal sodium excretion than low-dose prednisone.

Peri-coronary fat attenuation index combined with high-risk plaque characteristics quantified from coronary computed tomography angiography for risk stratification in new-onset chest pain individuals without acute myocardial infarction.

This study aims to evaluate the role of the peri-coronary Fat Attenuation Index (FAI) and High-Risk Plaque Characteristics (HRPC) in the assessment of coronary heart disease risk. By conducting coronary CT angiography and coronary angiography on 217 patients with newly developed chest pain (excluding acute myocardial infarction), their degree of vascular stenosis, FAI, and the presence and quantity of HRPC were assessed. The study results demonstrate a correlation between FAI and HRPC, and the combined use of FAI and HRPC can more accurately predict the risk of major adverse cardiovascular events (MACE). Additionally, the study found that patients with high FAI were more prone to exhibit high-risk plaque characteristics, severe stenosis, and multiple vessel disease. After adjustment, the combination of FAI and HRPC improved the ability to identify and reclassify MACE. Furthermore, the study identified high FAI as an independent predictor of MACE in patients undergoing revascularization, while HRPC served as an independent predictor of MACE in patients not undergoing revascularization. These findings suggest the potential clinical value of FAI and HRPC in the assessment of coronary heart disease risk, particularly in patients with newly developed chest pain excluding acute myocardial infarction.

Monocyte/High-Density Lipoprotein Ratio Is Associated with Atrial High-Rate Episodes within One Year Detected by Cardiac Implantable Electronic Devices.

OBJECTIVE: To investigate the risk factors for predicting atrial high-rate episodes (AHREs) detected by cardiac implantable electronic devices (CIEDs). METHODS: A total of 140 patients with CIED in our hospital from June 2013 to June 2018 were included and were followed up to observe whether they had AHREs. AHRE are defined as atrial rate ≥ 175 times/minute, lasting > 5 minutes, and reviewed by an experienced electrophysiologist with unclear clinical diagnosis. The patients fasted for 12 hours after implantation, and blood samples were collected for biochemical, lipid, and whole blood count detection. Follow-up was regular after discharge to record follow-up data of each patient and conduct statistical analysis. RESULTS: One hundred and forty patients were implanted with dual-chamber pacemakers, their median age was 70 years old, 44.29% were male, 27 patients had AHRE within one year, and AHRE incidence rate was 19.29%. The microcytic to hypochromic (M/H) ratio was calculated for all AHRE patients and compared with the patients without AHRE; the M/H value of AHRE patients was significantly higher. Throughout the entire follow-up period, a total of 44 patients developed AHRE; when adjusted by multivariate analysis, only M/H ratio ≥ 4.5 vs. < 4.5 had statistical significance, and the adjusted hazard ratio value was 4.313 (1.675-11.105). CONCLUSION: As an indicator, M/H ratio may play an important role in the occurrence and development of atrial fibrillation and can be used as a predictor of AHRE in patients with CIED.

The Predictive Value of Epicardial Fat Tissue Volume in the Occurrence and Development of Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background: Atrial fibrillation (AF) is one of the most common arrhythmias in clinical practice. Although fat is currently considered to be a risk factor for AF and a pathogenic link between epicardial fat tissue (EFT) and AF has been speculated, there are currently few clinical studies and literature data domestically or abroad. Objective: This study conducted a meta-analysis of observational case series studies to verify the relationship between atrial fibrillation and EFT and to strengthen the predictive value of EFT in the occurrence, development, and postablative recurrence of AF. Methods: We conducted a systematic search of the literature in electronic databases until December 2021 and supplemented this through manual searches of individual studies, reviewed articles, and reference lists in conference proceedings. This study conducted a meta-analysis to compare the differences between different populations, such as healthy participants and AF patients, healthy subjects and AF subtype cases, and paroxysmal and persistent AF with AF recurrence and without AF recurrence after ablation. Results: Following the retrieval of 828 articles, only 22 articles were selected as research results. Accordingly, the meta-analysis results show that the volume of EFT in AF is greater than that in healthy subjects (MD = 39.34 ml, 95% CI = 27.11, 51.58); persistent AF is greater than paroxysmal AF (MD = 14.37 ml, 95% CI = 7.46, 21.27); and recurrence after ablation is greater than without recurrence (MD = 14.37 ml, 95% CI = 7.46, 21.27). Conclusion: The results of this study further confirm the connection between EFT and AF and that EFT has a certain predictive value for the occurrence and development of AF.

Monocyte/High-Density Lipoprotein Ratio Is Associated with Atrial High-Rate Episodes within One Year Detected by Cardiac Implantable Electronic Devices

ABSTRACT Objective: To investigate the risk factors for predicting atrial high-rate episodes (AHREs) detected by cardiac implantable electronic devices (CIEDs). Methods: A total of 140 patients with CIED in our hospital from June 2013 to June 2018 were included and were followed up to observe whether they had AHREs. AHRE are defined as atrial rate ≥ 175 times/minute, lasting > 5 minutes, and reviewed by an experienced electrophysiologist with unclear clinical diagnosis. The patients fasted for 12 hours after implantation, and blood samples were collected for biochemical, lipid, and whole blood count detection. Follow-up was regular after discharge to record follow-up data of each patient and conduct statistical analysis. Results: One hundred and forty patients were implanted with dual-chamber pacemakers, their median age was 70 years old, 44.29% were male, 27 patients had AHRE within one year, and AHRE incidence rate was 19.29%. The microcytic to hypochromic (M/H) ratio was calculated for all AHRE patients and compared with the patients without AHRE; the M/H value of AHRE patients was significantly higher. Throughout the entire follow-up period, a total of 44 patients developed AHRE; when adjusted by multivariate analysis, only M/H ratio ≥ 4.5 vs. < 4.5 had statistical significance, and the adjusted hazard ratio value was 4.313 (1.675-11.105). Conclusion: As an indicator, M/H ratio may play an important role in the occurrence and development of atrial fibrillation and can be used as a predictor of AHRE in patients with CIED.

Prednisone in Uric Acid Lowering in Symptomatic Heart Failure Patients with Hyperuricemia -- The PUSH-PATH3 Study.

OBJECTIVE: To determine the safety and efficacy of prednisone in patients with symptomatic heart failure (HF) and hyperuricemia. METHODS: Prednisone therapy was administered for a short time to 191 symptomatic HF patients with hyperuricemia (serum uric acid > 7 mg/dl). RESULTS: Prednisone significantly reduced serum uric acid by 2.99 mg/dl (p < 0.01) and serum creatinine by 0.17 mg/dl (p < 0.01). These favorable effects were associated with a remarkable increase in urine output, improvement in renal function, and improvement in clinical status. CONCLUSION: Prednisone can be used safely in symptomatic HF patients with hyperuricemia.

Relationship between lipids levels and right ventricular volume overload in congestive heart failure.

BACKGROUND: The relationship between lipids and coronary artery disease has been well established. However, this is not the case between lipids and heart failure. Ironically, high lipid levels are associated with better outcomes in heart failure, but the mechanisms underlying the phenomenon are not fully understood. This study was performed to test the hypothesis that reduced intestinal lipid absorption due to venous congestion may lead to low lipid levels. METHODS: We collected data of clinical characteristics, echocardiograph, and lipid profile in 442 unselected patients with congestive heart failure. Correlations between lipid levels [including total cholesterol (TCL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG)] and right ventricle end diastolic diameter (RVEDD), left ventricle end diastolic diameter (LVEDD), right atrium diameter (RA), left atrium diameter (LA), or left ventricle ejection fraction (LVEF) were analyzed using Pearson correlation and partial correlation. RVEDD, LVEDD, RA, and LA were indexed to the body surface area. RESULTS: There was a significantly inverse correlation between TCL levels and RVEDD (r = -0.34, P < 0.001) and RA (r = -0.36, P < 0.001). Other lipids such as LDL-C, HDL-C, and TG had a similar inverse correlation with RVEDD and RA. All these correlations remained unchanged after adjusting for age, gender, smoking status, physical activity levels, comorbidities, and medication use. CONCLUSIONS: Lipid levels were inversely correlated to RVEDD in patients with congestive heart failure; however, because this was an observational study, further investigation is needed to verify our results as well as identify a causal relationship, if any.

Prednisone in Uric Acid lowering in Symptomatic Heart Failure Patients With Hyperuricemia (PUSH-PATH) study.

BACKGROUND: Chronic drug interactions that exist between symptomatic congestive heart failure (CHF) therapy and pharmacologic agents used for hyperuricemia and gout are a challenging problem in clinical practice. Recent observational studies showed that prednisone can induce a potent diuresis and lower serum uric acid concentration (SUA) in CHF. We therefore designed a randomized study to compare the effect of prednisone with allopurinol on SUA in symptomatic CHF patients with hyperuricemia. METHODS: Thirty-four symptomatic CHF participants with hyperuricemia (≥ 565 µmol/L) were randomized to receive prednisone (1 mg/kg/d, orally) or allopurinol (100 mg, thrice daily, orally) for 4 weeks. The primary outcome measure was change from baseline in SUA. The secondary outcome measures were change from baseline in serum creatinine levels, estimated glomerular filtration rate, daily urine output, body weight, N-terminal pro-B-type natriuretic peptide levels, physician-assessed global clinical status, and New York Heart Association functional class. RESULTS: Both prednisone and allopurinol greatly lowered SUA rapidly. The overall SUA-lowering effect did not differ between treatment groups during the study period (P = 0.48, 2-way repeated measures analysis of variance). However, prednisone increased estimated glomerular filtration rate and daily urine output, and lowered body weights and N-terminal pro-B-type natriuretic peptide. Consequently, participants treated with prednisone had an improvement in clinical status. CONCLUSIONS: The study showed that the SUA-lowering effect of prednisone and allopurinol is similar in symptomatic CHF patients. Prednisone might be useful for short-term SUA-lowering in CHF patients with hyperuricemia.

Serum uric acid as an index of impaired renal function in congestive heart failure.

BACKGROUND: Hyperuricemia is frequently present in patients with heart failure. Many pathological conditions, such as tissue ischemia, renal function impairment, cardiac function impairment, metabolic syndrome, and inflammatory status, may impact uric acid (UA) metabolism. This study was to assess their potential relations to UA metabolism in heart failure. METHODS: We retrospectively assessed clinical characteristics, echocardiological, renal, metabolic and inflammatory variables selected on the basis of previous evidence of their involvement in cardiovascular diseases and UA metabolism in a large cohort of randomly selected adults with congestive heart failure (n = 553). By clustering of indices, those variables were explored using factor analysis. RESULTS: In factor analysis, serum uric acid (SUA) formed part of a principal cluster of renal functional variables which included serum creatinine (SCr) and blood urea nitrogen (BUN). Univariate correlation coefficients between variables of patients with congestive heart failure showed that the strongest correlations for SUA were with BUN (r = 0.48, P < 0.001) and SCr (r = 0.47, P < 0.001). CONCLUSIONS: There was an inverse relationship between SUA levels and measures of renal function in patients with congestive heart failure. The strong correlation between SUA and SCr and BUN levels suggests that elevated SUA concentrations reflect an impairment of renal function in heart failure.

Prednisone adding to usual care treatment for refractory decompensated congestive heart failure.

The aim of the present study was to determine if prednisone, a glucocorticoid, added to conventional treatment for patients with decompensated congestive heart failure (DCHF) refractory to the conventional care, results in significant relief of congestive symptoms and improvement of clinical status. Diuretic-based strategies, as the mainstay in DCHF management, are not always effective in eliciting diuresis. However, the addition of prednisone to standard care may induce potent diuresis in this clinical setting. Thirty-five patients with DCHF were enrolled in the study, and prednisone (1 mg/kg/day with maximum dosage of 60 mg/day) was added to the standard treatment. Primary endpoints were the effects on daily urine volume, patient and physician assessed dyspnea and global clinical status, and changes in renal function. The addition of prednisone induced potent diuresis with time. As a result of the diuresis, congestive symptoms improved markedly in 80% and global clinical status improved markedly in 68.6% of the DCHF patients at the end of the study (P < 0.001). The change in serum creatinine from baseline was -12.21 micromol/L (P < 0.05). Adding prednisone to conventional care in the patients with refractory DCHF induced potent diuresis accompanied by a dramatic relief of congestive symptoms and improvements in clinical status and renal function.