Semaglutide for the prevention of atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, is reported to have cardiac benefits, but its effects on preventing atrial fibrillation (AF) remain inconclusive. This study aimed to investigate whether semaglutide can prevent AF occurrence in patients with type 2 diabetes mellitus (T2DM), obesity, or overweight. METHODS: We searched MEDLINE, EMBASE, the Cochrane CENTRAL database, and clinicaltrials.gov from inception to December 29, 2023. Randomized controlled trials of semaglutide in patients with T2DM, obesity, or overweight were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95 % confidence intervals (CIs) were calculated for the overall population and subgroups. RESULTS: Twenty-one trials comprising 25957 patients were included. In the overall pooled analysis, semaglutide decreased AF occurrence compared to control drugs (RR 0.70, 95 % CI 0.52-0.95). This result was consistent in trials using other antihyperglycemic medications as controls (RR 0.43, 95 % CI 0.21-0.89), but not in placebo-controlled trials (RR 0.77, 95 % CI 0.56-1.07). The outcome was favorable for patients with T2DM (RR 0.71, 95 % CI 0.52-0.97), but not for patients with overweight or obesity (RR 0.56, 95 % CI 0.18-1.73). Results varied by type of semaglutide, with oral semaglutide showing an RR of 0.49 (95 % CI 0.25-0.97) and subcutaneous semaglutide showing an RR of 0.77 (95 % CI 0.55-1.07). CONCLUSION: Semaglutide was associated with a reduced risk of AF occurrence in the overall analysis. Favorable outcomes were observed in subsets using other antihyperglycemic medications as controls, in patients with T2DM, and with oral semaglutide.

Activation pattern of the coronary sinus facilitates the differentiation for ventricular outflow tract arrhythmias.

INTRODUCTION: The accuracy of surface ECG algorithms for predicting the origin of outflow tract ventricular arrhythmias (OT-VAs) might be questioned. Intracardiac electrograms recorded at anatomic landmarks could provide new predictive insights. We aim to evaluate the efficacy of a novel criterion utilizing the activation pattern of the coronary sinus (CS) in localizing OT-VAs, including VAs originating from the right ventricular outflow tract (RVOT), endocardial left ventricular outflow tract (Endo-LVOT), and epicardial left ventricular outflow tract (Epi-LVOT). METHODS: We measured the ventricular activation time of the mitral annulus (MA) from the onset of the earliest QRS complex of VAs to the initial deflection over the isoelectric line at local signals, namely the QRS-MA interval. The activation at 3 and 12 o'clock of the MA was recorded as the QRS-MA3 and QRS-MA12 intervals, respectively. Their predictive values were compared to previous ECG algorithms. RESULTS: A total of 68 patients with OT-VAs were enrolled (51 for development and 17 for validation). From early to late, the ventricular activation sequences at MA12 were as follows: Epi-LVOT, Endo-LVOT, and RVOT. In LBBB morphology OT-VAs, the QRS-MA12 interval was significantly earlier for LVOT origins than RVOT origins. In the combined cohort of development and validation cohort, a cut-off value of ≤10 ms predicted the LVOT origin with a sensitivity of 100% and specificity of 78%. The QRS-MA12 interval ≤ -24 ms additionally predicted epicardial LVOT sites of origin. CONCLUSIONS: The QRS-MA interval could accurately differentiate the OT-VAs localization.

Azvudine for the Treatment of COVID-19 in Pre-Existing Cardiovascular Diseases: A Single-Center, Real-World Experience.

COVID-19 can lead to adverse outcomes in patients with pre-existing diseases. Azvudine has been approved for treating COVID-19 in China, but the real-world data is limited. It is aimed to investigate the efficacy of Azvudine in patients with COVID-19 and pre-existing cardiovascular diseases. Patients with confirmed COVID-19 and pre-existing cardiovascular diseases are retrospectively enrolled. The primary outcome is all-cause death during hospitalization. Overall, 351 patients are included, with a median age of 74 years, and 44% are female. 212 (60.6%) patients are severe cases. Azvudine is used in 106 (30.2%) patients and not in 245 (69.8%). 72 patients died during hospitalization. After multivariate adjustment, patients who received Azvudine a lower risk of all-cause death (hazard ratio: 0.431; 95% confidence interval: 0.252-0.738; p = 0.002) than controls. Azvudine therapy is also associated with lower risks of shock and acute kidney injury. For sensitivity analysis in the propensity score-matched cohort (n = 90 for each group), there is also a significant difference in all-cause death between the two groups (hazard ratio: 0.189; 95% confidence interval: 0.071-0.498; p < 0.001). This study indicated that Azvudine therapy is associated with better outcomes in COVID-19 patients with pre-existing cardiovascular diseases.

Prognostic significance of quantitative electrocardiographic parameters in patients with non-high-risk pulmonary embolism.

BACKGROUND: Electrocardiogram (ECG) abnormalities indicating right ventricular strain have been reported to have prognostic value in severe cases of acute pulmonary embolism (PE). We aimed to analyze the prognostic significance of other quantitative ECG parameters in non-high-risk acute PE. METHODS: Consecutive patients with non-high-risk acute PE were prospectively enrolled. The following baseline ECG parameters were collected: rhythm, heart rate, QRS axis, right bundle branch block (RBBB) pattern, S1Q3T3 pattern, T-wave inversion, ST-segment elevation, Qr in lead V1, PR Interval, QRS complex duration, QT interval, P-wave amplitude and duration, R- and S-wave amplitudes. The primary endpoint was early discharge within three days. Associations between ECG parameters and early discharge were analyzed. RESULTS: Overall, 383 patients were enrolled (median age: 67 years, 57% female): 277 (72.3%) with low-risk and 106 (27.7%) with intermediate-risk. The two groups of patients differed in several ECG signs of right ventricular strain and many other quantitative parameters like R- and S-wave amplitudes. In the multivariate logistic regression analysis, the S-wave depth in lead V5 (S-V5) was the only independent prognostic factor for early discharge (odds ratio = 0.137, 95% confidence interval = 0.031-0.613, p = 0.009). The optimum cutoff value of S-V5 for predicting early discharge derived from the receiver operative characteristic curve was 0.15 mv (c-statistic = 0.66, p =0.003). CONCLUSIONS: Several ECG signs of right ventricular strain and many other quantitative parameters were associated with disease severity in non-high-risk acute PE. An S-V5 lesser than 0.15 mv was predictive for early discharge in these patients.

Angiographic assessment of vein of Marshall in atrial fibrillation: Implications for identification and cannulation.

Background: The vein of Marshall (VOM) ethanol infusion improves rhythm control in atrial fibrillation (AF). The identification and cannulation of the VOM can be technically challenging. This study aimed to assess the angiographic morphology of the VOM and investigate its value in the VOM ethanol infusion. Methods: Patients with AF (n = 162) scheduled for combined catheter ablation and VOM ethanol infusion were enrolled. The VOM morphologic features in the right anterior oblique (RAO), the left anterior oblique (LAO), and the LAO cranial views were analyzed. The impact of morphology on the identification and cannulation of the VOM was investigated. Results: The VOM was identified in 159 (98.1 %) and cannulated in 150 (92.6 %) patients. The VOM identification rate in the RAO and LAO/LAO cranial view was 97.3 % and 89.3 %, respectively. Of 134 patients with VOM identification in the LAO/LAO cranial view, 104 (77.6 %) had a VOM ostium clock location (VOMoClock) of ≤3 and 3-4 o'clock. The VOM cannulation success rate in the ≤3, 3-4, 4-5, and 5-6 o'clock groups was 100 %, 92.6 %, 88.5 %, and 77.8 %, respectively (p = 0.032). The median (interquartile range) cannulation time in the four groups was 10.5 (6.3), 12.0 (9.0), 13.0 (23.0), and 34.0 (30.0) minutes, respectively (p < 0.001). The diameter of the coronary sinus ostium in the RAO view and the VOMoClock were independent predictors for difficult cannulation. Conclusions: The VOM morphologic features in different angiographic views provide valuable information which could facilitate the identification and cannulation of the VOM.

SGLT2 inhibitors for the prevention of atrial fibrillation: a systemic review and meta-analysis.

AIMS: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are reported to have cardiac benefits. The effects of SGLT2 inhibitors on the prevention of atrial fibrillation (AF) remain inconclusive. We aimed to investigate whether SGLT2 inhibitors can prevent AF occurrence in patients with cardiometabolic diseases. METHODS: We searched MEDLINE, EMBASE, and the Cochrane CENTRAL database up to July 1, 2023. Randomized, placebo-controlled trials of SGLT2 inhibitors in patients with diabetes, heart failure, chronic kidney diseases, or cardiometabolic risk factors were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated in the overall population and selected subgroups. RESULTS: Forty-six trials comprising 101 100 patients were included. Overall, no significant risk reduction of AF occurrence was observed with SGLT2 inhibitors, although there was a favorable trend (RR 0.90, 95% CI 0.80-1.01). In trials with follow-up durations of over one year, a similar result was achieved (RR 0.90, 95% CI 0.80-1.01). The results were consistent across different SGLT2 inhibitors, with RRs (95%CIs) of 0.82 (0.60-1.12) for canagliflozin, 0.87 (0.73-1.03) for dapagliflozin, 0.97 (0.78-1.22) for empagliflozin, 0.99 (0.66-1.50) for sotagliflozin, and 0.87 (0.58-1.29) for ertugliflozin. Analyses in different doses of SGLT2 inhibitors yielded similar results. The associations between SGLT2 inhibitors and AF occurrence were also absent in patients with diabetes, heart failure, and chronic kidney diseases. CONCLUSION: For patients with cardiometabolic diseases or risk factors, SGLT2 inhibitors did not decrease the risk of AF occurrence, regardless of follow-up duration, type or dose of the drug, or the patient population.

The effects of SGLT2 inhibitors on the prevention of atrial fibrillation (AF) remain inconclusive. For patients with cardiometabolic diseases or risk factors, SGLT2 inhibitors did not decrease the risk of AF occurrence, regardless of follow-up duration, type or dose of the drug, or the patient population. Further research is warranted to investigate the potential benefit of SGLT2 inhibitors in AF.

Double-wire technique to facilitate vein of Marshall cannulation and ethanol infusion in atrial fibrillation: a case series.

BACKGROUND: The vein of Marshall (VOM) ethanol infusion is increasingly performed in combination with catheter ablation in atrial fibrillation (AF). The cannulation of the VOM can sometimes be challenging. This study aimed to evaluate the double-wire technique in cases of difficult cannulation of the VOM. CASE PRESENTATION: Patients with AF scheduled for combined catheter ablation and VOM ethanol infusion were consecutively enrolled. The procedure was performed via the femoral vein. If the regular cannulation technique with one angioplasty wire failed or took more than 20 min, the double-wire technique using a stabilizing wire and a cannulation wire was performed. The unique technique was used mainly in two scenarios, when the Eustachian ridge was too prominent as a barrier for catheter manipulation or when the VOM ostium was close to the coronary sinus ostium. Of 162 patients scheduled for VOM ethanol infusion, the double-wire technique was applied in 6 (3.7%) patients and led to a 100% successful cannulation rate of the VOM. Of the six patients, two had a prominent Eustachian ridge, and four had a VOM ostium close to the coronary sinus ostium. The mean cannulation time was 33.3 ± 7.3 min. The ethanol infusion was successfully performed in 5 patients. One patient had a collateral circulation in the distal VOM, and ethanol infusion was not performed. CONCLUSIONS: The double-wire technique can facilitate VOM cannulation and ethanol infusion in challenging cases. WORD COUNT: 231.

Role of macrophages in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary vascular disease characterized by progressive pulmonary artery pressure elevation, increased pulmonary vascular resistance and ultimately right heart failure. Studies have demonstrated the involvement of multiple immune cells in the development of PAH in patients with PAH and in experimental PAH. Among them, macrophages, as the predominant inflammatory cells infiltrating around PAH lesions, play a crucial role in exacerbating pulmonary vascular remodeling in PAH. Macrophages are generally polarized into (classic) M1 and (alternative) M2 phenotypes, they accelerate the process of PAH by secreting various chemokines and growth factors (CX3CR1, PDGF). In this review we summarize the mechanisms of immune cell action in PAH, as well as the key factors that regulate the polarization of macrophages in different directions and their functional changes after polarization. We also summarize the effects of different microenvironments on macrophages in PAH. The insight into the interactions between macrophages and other cells, chemokines and growth factors may provide important clues for the development of new, safe and effective immune-targeted therapies for PAH.

Characteristics of exercise intolerance in different subgroups of pulmonary arterial hypertension associated with congenital heart disease.

BACKGROUND: Exercise intolerance is a major manifestation of pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). We aimed to investigate the characteristics of exercise intolerance in different subgroups of PAH-CHD. METHODS: We retrospectively enrolled 171 adult patients with PAH-CHD and 30 age and sex-matched healthy subjects and performed cardiopulmonary exercise testing. Gas exchange parameters, including peak oxygen uptake (peak V̇o2), anaerobic threshold, and the slope of ventilatory equivalent for carbon dioxide (V̇e/V̇co2 slope), were recorded. RESULTS: The median age of patients at enrollment was 27.8 years, and 131 (76.6%) were female. Peak V̇o2 was reduced in patients compared to healthy controls (median, 14.8 ml/kg/min versus 26.9 ml/kg/min, p < 0.001). Of all 171 patients, 60 (35.1%) had Eisenmenger syndrome, 35 (20.5%) had PAH associated with systemic-to-pulmonary shunts (PAH-SP), 39 (22.8%) had PAH with small defects (PAH-SD), and 37 (21.6%) had PAH after cardiac defect correction (PAH-CD). Patients with Eisenmenger syndrome had the lowest peak V̇o2 (p = 0.003) and the highest V̇e/V̇co2 slope (p = 0.012), compared with other patients, representing the worst exercise capacity and ventilatory efficiency. Patients with PAH-SP had the best exercise capacity among the four groups, indicated by the highest peak V̇o2 (p = 0.003) compared with other patients. Peak V̇o2 was negatively correlated with pulmonary vascular resistance (r = -0.411, p < 0.001). CONCLUSIONS: Exercise capacity was severely reduced in patients with PAH-CHD. Among the four subgroups, patients with Eisenmenger syndrome had the worst exercise capacity and ventilatory efficiency.

[Dissolution test and evaluation of Guizhi Fuling Capsules].

Because of the complex components, simple content determination can hardly reflect the overall quality of Guizhi Fuling Capsules. Therefore, it is necessary to carry out a multi-component dissolution test. The variability of quality among different batches of products from different manufacturers is a common problem of Chinese medicine solid preparations. To comprehensively control the quality of Guizhi Fuling Capsules, we studied the dissolution behaviors of 7 index components in the capsules under different conditions, and investigated the consistency of dissolution behaviors among different batches of products from the same manufacturer. The basket method of general rule 0931 in Chinese Pharmacopoeia was adopted, and the rotating speeds were set at 50, 75, and 100 r·min~(-1), respectively. The hydrochloric acid solution(pH 1.2), acetate buffer solution(pH 4.0), pure water, and phosphate buffer solution(pH 6.8) were used as the dissolution media. Automatic sampling was carried out at the time points of 5, 10, 20, 30, 45, and 60 min, respectively. The cumulative dissolution of 7 index components was measured through ultra-performance liquid chromatography(UPLC). The difference factor f_1 and similarity factor f_2 were calculated to comprehensively evaluate the similarity of the dissolution curves among 8 batches of Guizhi Fuling Capsules, and a variety of dissolution and release equations were fitted. The results showed that multiple components had faster dissolution rates at higher rotating speed and in hydrochloric acid medium. The 8 batches of Guizhi Fuling capsules showed the average f_1 value lower than 15 and the average f_2 value higher than 50, which indicated that different batches of products had similar dissolution behaviors. Most components had synchronous dissolution behaviors and similar release cha-racteristics. This study provides a reference for the quality consistency evaluation among batches, processing optimization, and dosage form improvement of Guizhi Fuling Capsules.

Characteristics of Primary Bradyarrhythmia in Hypertrophic Cardiomyopathy: A 10-Year, Single-Center Analysis.

BACKGROUND: Secondary bradyarrhythmias in hypertrophic cardiomyopathy (HCM) have been extensively reported. The prevalence and characteristics of primary bradyarrhythmias in HCM have yet to be investigated. METHODS: We retrospectively enrolled 101 consecutive patients with HCM who were referred to the arrhythmia center from May 2010 to October 2020. The clinical features of patients with bradyarrhythmias were analyzed. RESULTS: Twenty-nine (28.7%) patients had primary bradyarrhythmias, and six (5.9%) patients had secondary third-degree atrioventricular block (AVB). Of the 29 patients, 17 (58.6%) had sinus node dysfunction (SND), 14 (48.3%) had AVB, and two (6.9%) had both SND and AVB. The median age was 62 years old, and 69% were male. Six (20.7%) patients had left ventricular obstructive outflow tract obstruction, 15 (51.7%) had a history of syncope, and one (3.4%) had a family history of HCM. Most patients (86.2%) had New York Heart Association functional class I or II, and the median left ventricular ejection fraction was 63%. A total of 22 patients received pacemaker implantation, including 17 (77.3%) dual-chamber pacing, four (18.2%) single-chamber ventricular pacing, and one (4.5%) cardiac resynchronization therapy. CONCLUSIONS: Primary bradyarrhythmias need to be evaluated in HCM patients with arrhythmia-related symptoms. Patients with HCM might need pacemaker implantation for primary bradyarrhythmias.

Occluding morphologically complicated left atrial appendage using the small-umbrella LAmbre device.

BACKGROUND: Percutaneous left atrial appendage (LAA) occlusion is effective for stroke prevention in patients with atrial fibrillation. LAA can have a complex anatomy, such as multiple lobes or a large orifice, which may render it unsuitable for occlusion using regular devices. We aimed to investigate the feasibility, safety, and short-term efficacy of the small-umbrella LAmbre device for morphologically complicated LAA. METHODS: We retrospectively enrolled 129 consecutive patients who underwent LAA occlusion using the LAmbre device; the small-umbrella LAmbre device was used in 30 of these patients. We analyzed patients' characteristics, procedural details, and outcomes. RESULTS: Twenty-two patients (73.3%) had multilobed (≥ 2) LAA. The umbrella of the occluder was anchored in the branch in 9 patients and in the common trunks of branches in 13 patients. The landing zone and orifice diameters were 19.0 ± 4.39 mm and 27.4 ± 3.95 mm, respectively. The sizes of the umbrella and occluder cover were 22.0 ± 3.42 mm and 34.3 ± 2.75 mm, respectively. At 3-month follow-up transesophageal echocardiography in 24 patients, no peri-device residual flow was reported. Device thrombosis was detected in one patient at 3 months and disappeared after 3 months of anticoagulation. Ischemic stroke occurred in one patient; no other adverse events were reported. CONCLUSIONS: Occlusion of morphologically complicated LAA using the small-umbrella LAmbre device was feasible, safe, and effective in patients with atrial fibrillation in this study. This occluder provides an alternative for patients who cannot be treated with regular-sized LAA occlusion devices.

Tracking the Stepwise Formation of a Water-Soluble Fluorescent Tb12 Cluster for Efficient Doxorubicin Detection.

Doxorubicin (DOX) is an anthraquinone drug used for the efficient treatment of a variety of tumors in human beings. Unfortunately, its poor biodegradability causes incomplete metabolism in the body. Therefore, it is of great significance to synthesize a sensitive and selective material for DOX detection. In this paper, we report a water-soluble Tb12 cluster and track its step-by-step formation (L → Tb1L1 → Tb2L1 → Tb2L2 → Tb3L2 → Tb4L2 → Tb12L6). Tb12 can be used to determine the presence of DOX, which quenches the luminescence of the Tb12 aqueous solution, and the detection limit can reach 13 nM (KSV = 8.7 × 105 M-1). Tb12 has advantages of high sensitivity and high selectivity for the detection of DOX in a simulated environment of human urine and serum.

Characteristics and Long-Term Ablation Outcomes of Supraventricular Arrhythmias in Hypertrophic Cardiomyopathy: A 10-Year, Single-Center Experience.

Background: A variety of supraventricular arrhythmias (SVAs) may occur in patients with hypertrophic cardiomyopathy (HCM). The characteristics and long-term ablation outcomes of different types of SVAs in HCM have not been comprehensively investigated. Methods: We retrospectively enrolled 101 consecutive patients with HCM who were referred to the electrophysiology and arrhythmia service from May 2010 to October 2020. The clinical features and ablation outcomes were analyzed. Results: Seventy-eight patients had SVAs, which comprised 50 (64.1%) cases of atrial fibrillation (AF), 16 (20.5%) of atrial flutter (AFL), 15 (19.2%) of atrioventricular reentrant tachycardia (AVRT), 11 (14.1%) of atrial arrhythmia (AT), and 3 (3.8%) of atrioventricular nodal reentrant tachycardia (AVNRT). Thirty-four patients underwent catheter ablation and were followed up for a median (interquartile range) of 58.5 (82.9) months. There was no recurrence in patients with non-AF SVAs. In patients with AF, the 1- and 7-year AF-free survival rates were 87.5 and 49.5%, respectively. A receiver operator characteristic analysis showed that a greater left ventricular end-diastolic dimension (LVEDD) was associated with a higher recurrence of AF, with an optimum cutoff value of 47 mm (c-statistic = 0.91, p = 0.011, sensitivity = 1.00, specificity = 0.82). In Kaplan-Meier analysis, patients with a LVEDD ≥ 47 mm had worse AF-free survival than those with a LVEDD <47 mm (log-rank p = 0.014). Conclusions: In this unique population of HCM, AF was the most common SVA, followed in order by AFL, AVRT, AT, and AVNRT. The long-term catheter ablation outcome for non-AF SVAs in HCM is satisfactory. A greater LVEDD predicts AF recurrence after catheter ablation in patients with HCM.

Identification of Hypoxia Induced Metabolism Associated Genes in Pulmonary Hypertension.

Objective: Pulmonary hypertension (PH) associated with hypoxia and lung disease (Group 3) is the second most common form of PH and associated with increased morbidity and mortality. This study was aimed to identify hypoxia induced metabolism associated genes (MAGs) for better understanding of hypoxic PH. Methods: Rat pulmonary arterial smooth muscle cells (PASMCs) were isolated and cultured in normoxic or hypoxic condition for 24 h. Cells were harvested for liquid chromatography-mass spectrometry analysis. Functional annotation of distinguishing metabolites was performed using Metaboanalyst. Top 10 enriched metabolite sets were selected for the identification of metabolism associated genes (MAGs) with a relevance score >8 in Genecards. Transcriptomic data from lungs of hypoxic PH in mice/rats or of PH patients were accessed from Gene Expression Omnibus (GEO) database or open-access online platform. Connectivity Map analysis was performed to identify potential compounds to reverse the metabolism associated gene profile under hypoxia stress. The construction and module analysis of the protein-protein interaction (PPI) network was performed. Hub genes were then identified and used to generate LASSO model to determine its accuracy to predict occurrence of PH. Results: A total of 36 altered metabolites and 1,259 unique MAGs were identified in rat PASMCs under hypoxia. 38 differentially expressed MAGs in mouse lungs of hypoxic PH were revealed, with enrichment in multi-pathways including regulation of glucose metabolic process, which might be reversed by drugs such as blebbistatin. 5 differentially expressed MAGs were displayed in SMCs of Sugen 5416/hypoxia induced PH rats at the single cell resolution. Furthermore, 6 hub genes (Cat, Ephx1, Gpx3, Gstm4, Gstm5, and Gsto1) out of 42 unique hypoxia induced MAGs were identified. Higher Cat, Ephx1 and lower Gsto1 were displayed in mouse lungs under hypoxia (all p < 0.05), in consistent with the alteration in lungs of PH patients. The hub gene-based LASSO model can predict the occurrence of PH (AUC = 0.90). Conclusion: Our findings revealed six hypoxia-induced metabolism associated hub genes, and shed some light on the molecular mechanism and therapeutic targets in hypoxic PH.

Corrigendum: Identification of Hypoxia Induced Metabolism Associated Genes in Pulmonary Hypertension.

[This corrects the article DOI: 10.3389/fphar.2021.753727.].