Biochanin A inhibits cardiac hypertrophy and fibrosis in vivo and in vitro.

The heart undergoes pathological cardiac hypertrophy as an adaptive response to prolonged pathological stimulation, leading to cardiomyocyte hypertrophy, fibroblast proliferation, and an increase in extracellular matrix. Chinese medicine monomers are now receiving much attention for the treatment of cardiac hypertrophy and myocardial remodeling. Biochanin A (BCA) is a kind of flavonoid structural monomer, which has a certain therapeutic effect on bone thinning disease, aging syndrome, lung cancer, etc. Moreover, it exhibits hypoglycemic, anti-inflammatory, anti-oxidation, anti-bacteria and other pharmacological properties. It is still unknown whether BCA has an impact on the mechanism of TAC-induced cardiac hypertrophy. Here, cardiac remodeling was induced by TAC. BCA was injected intraperitoneally at 25 and 50 mg/kg/day one week in advance. Masson, WGA, DHE and other pathological staining and serum were used to detect the inhibitory effect of BCA on cardiac hypertrophy in mice. The anti-hypertrophic effect of BCA was demonstrated by studying the pathological manifestations of Neonatal rat cardiomyocytes (NRCMs) and cardiac fibroblasts (CFs) in vitro. The results showed that BCA significantly reduced TAC-induced fibrosis, inflammation, oxidative stress, and myocardial hypertrophy. BCA inhibited Ang II-induced cell hypertrophy and oxidative stress in NRCMs in vitro and Ang II-induced CF migration, proliferation, and collagen secretion. This suggests that BCA plays a key role in inhibiting the progression of myocardial remodeling, suggesting that BCA may be a promising agent for the treatment of myocardial hypertrophy and fibrosis.

Long duration of atrial high-rate episode is more favorable in predicting ischemic stroke than high CHA2 DS2 -VASc score.

OBJECTIVE: This study aimed to explore the roles of duration and burden of atrial high-rate episode (AHRE) on ischemic stroke in patients with pacemaker implantation. METHODS: Patients with pacemaker implantation for bradycardia from 2013 to 2017 were consecutively enrolled. Data such as gender, age, combined diseases, type of AF, left atrial size, left ventricular size, left ventricular ejection fraction, CHA2 DS2 -VASc score, and anticoagulants were collected. The burden and duration of AHRE based on different interval partition were also recorded in detail to evaluate the impacts on ischemic stroke. Cox regression analysis with time-dependent covariates was conducted. RESULTS: A total of 220 patients with AHRE were enrolled. The average follow-up time was 48.42 ± 17.20 months. Univariate regression analysis showed that diabetes (p = .024), high CHA2 DS2 -VASc score (≥ 2) (p = .021), long mean AHRE burden (p = .011), long maximal AHRE burden (p = .015), long AHRE duration lasting≥48 h (p = .001) or 24 h (p = .001) or 12 h (p = .005) were prone to ischemic stroke. Further multivariate regression analysis showed that long duration of AHRE (≥48 h) (HR 10.77; 95% CI 3.22-55.12; p = .030) were significantly correlated with stroke in patients with paroxysmal AF. There was no significant correlation between the type of AF and stroke (p = .927). CONCLUSION: The longer duration of AHRE (≥48 h) was more favorable in predicting ischemic stroke than high CHA2 DS2 -VASc score (≥2).

Conduction system pacing improves the outcomes on patients with high percentage of ventricular pacing and heart failure with mildly reduced ejection fraction.

Aims: This study aimed to investigate the efficacy and safety of CSP in patients with a high percentage of ventricular pacing and heart failure with HFmrEF. Methods: Patients who underwent CSP for HFmrEF and ventricular pacing >40% were consecutively enrolled from January 2018 to May 2021. All participants were followed up at least 12 months. Clinical data including cardiac performance and lead outcomes were compared before and after the procedure. Left ventricular ejection fraction (LVEF) was measured using the biplane Simpson's method. HFmrEF was defined as heart failure with the LVEF ranging from 41%-49%. Results: CSP was successfully performed in 64 cases (96.97%), which included 16 cases of left bundle branch pacing (LBBP) and 48 cases of His bundle pacing (HBP). After a mean of 23.12 ± 8.17 months follow-up, NYHA classification (P < 0.001), LVEF (42.45 ± 1.84% vs. 49.97 ± 3.57%, P < 0.001) and left ventricular end diastolic diameter (LVEDD) (55.59 ± 6.17 mm vs. 51.66 ± 3.48 mm, P < 0.001) improved significantly. During follow-up, more than half (39/64,60.9%) of patients returned to normal LVEF and LVEDD with complete reverse remodeling. The pacing threshold in LBBP was lower (0.90 ± 0.27 V@0.4 ms vs. 1.61 ± 0.71 V@0.4 ms, P < 0.001) than that in HBP. No perforation, electrode dislodging, thrombosis or infection was observed during follow-up. Conclusions: CSP could improve the clinical outcomes in patients with HFmrEF and a high percentage of ventricular pacing. LBBP might be a better choice because of its feasibility and safety, especially in patients with infranodal atrioventricular block.

Cumulative non-high-density lipoprotein cholesterol burden and risk of atherosclerotic cardiovascular disease: a prospective community-based study.

Background: The relationship between cumulative non-high-density lipoprotein cholesterol (non-HDL-C) burden and atherosclerotic cardiovascular disease (ASCVD) remains unclear. Objective: To prospectively examine the association between cumulative non-HDL-C burden and ASCVD risk in the Kailuan cohort of China. Methods: A total of 49,679 subjects who were free of ASCVD participated in three consecutive examinations in 2006, 2008 and 2010 were enrolled. Duration and concentration of cumulative exposure to non-HDL-C (cumNon-HDL-C) were respectively used to estimate the extent of cumulative non-HDL-C burden. The participants were divided into four groups according to durations of cumNon-HDL-C (0, 2, 4 and 6 years) and five groups according to the quintiles of cumNon-HDL-C concentration (<10.93, 10.93-12.68, 12.69-14.32, 14.33-16.72 and ≥16.73 mmol/L). Cox regression models were used to analyze the influence of cumulative non-HDL-C burden on ASCVD risk. Results: We identified 1,134 incident ASCVD cases during a mean of 4.89 years of follow-up. Multivariable adjusted analysis revealed that compared with no exposure, cumNon-HDL-C duration 2, 4 and 6 years increased ASCVD risk by 26% (HR: 1.26, 95% CI: 1.07-1.47), 56% (HR: 1.56, 95% CI: 1.31-1.86) and 91% (HR: 1.91, 95% CI: 1.59-2.31) respectively; The hazard ratios (HRs) for the fourth and fifth versus lowest quintile of cumNon-HDL-C concentration were 1.25 and 1.72 for ASCVD. Each standard deviation increment in cumNon-HDL-C concentration was associated with a 10% increased risk of ASCVD. Conclusion: Long-term and higher cumNon-HDL-C were all significantly associated with an increased risk of ASCVD independent of single non-HDL-C level.

Predictors of pacing-induced cardiomyopathy detection and outcomes demonstration after conduction system pacing upgrade on patients with long-term persistent atrial fibrillation.

OBJECTIVE: To identify the predictors of pacing-induced cardiomyopathy (PICM) and illustrate the safety and feasibility of conduction system pacing (CSP) upgrade on patients with long-term persistent atrial fibrillation (AF). METHODS: All patients with long-term persistent AF and normal left ventricular ejection fraction (LVEF) ≥50% were consecutively enrolled from January 2008 to December 2017, and all the patients with atrioventricular block (AVB) and high right ventricular pacing (RVP) percentage of at least 40%. The predictors of PICM were identified, and patients with PICM were followed up for at least 1 year regardless of CSP upgrade. Cardiac performances and lead outcomes were investigated in all patients before and after CSP upgrade. RESULTS: The present study included 139 patients, out of which 37 (26.62%) developed PICM, resulting in a significant decrease in the left ventricular ejection fraction (LVEF) from 56.11 ± 2.56% to 38.10 ± 5.81% (p< .01). The median duration for the development of PICM was 5.43 years. Lower LVEF (≤52.50%), longer paced QRS duration (≥175 ms), and higher RVP percentage (≥96.80%) were identified as independent predictors of PICM. Furthermore, the morbidity of PICM progressively increased with an increased number of predictors. The paced QRS duration (183.90 ± 22.34 ms vs. 136.57 ± 20.71 ms, p < .01), LVEF (39.35 ± 2.71% vs. 47.50 ± 7.43%, p < .01), and left ventricular end-diastolic diameter (LVEDD) (55.53 ± 5.67 mm vs. 53.20 ± 5.78 mm, p = .03) improved significantly on patients accepting CSP upgrade. CSP responses and complete reverse remodeling (LVEF ≥50% and LVEDD < 50 mm) were detected in 80.95% (17/21) and 42.9% (9/21) of patients. The pacing threshold (1.52 ± 0.78 V/0.4 ms vs. 1.27 ± 0.59 V/0.4 ms, p = .16) was stable after follow-up. CONCLUSION: PICM is very common in patients with long-term persistent AF, and CSP upgrade was favorable for better cardiac performance in this patient population.

The pathogenesis of aging-induced left atrial appendage thrombus formation and cardioembolic stroke in mice is influenced by inflammation-derived matrix metalloproteinases.

Elderly people without atrial fibrillation (AF) still have a high incidence of cardioembolic stroke, suggesting that thrombus formation within the left atrial appendage (LAA) may also occur in an AF-independent manner. In the present study, we explored the potential mechanisms for aging-induced LAA thrombus formation and stroke in mice. We monitored stroke events in 180 aging male mice (14-24 months) and assessed left atrium (LA) remodeling by echocardiography at different ages. Mice that had stroke were implanted with telemeters to confirm AF. Histological features of LA and LAA thrombi were examined, as well as collagen content, expression of matrix metalloproteinases (MMPs), and leukocyte density in the atria at different ages, in mice with or without stroke. Also, the effects of MMP inhibition on stroke incidence and atrial inflammation were tested. We detected 20 mice (11 %) with stroke, 60 % of which were within 18-19 months of age. Although we did not detect AF in mice with stroke, we detected the presence of LAA thrombi, suggesting that stroke originated from the hearts of these mice. Compared with 18-month-old mice without stroke, 18-month-old stroke mice had enlarged LA with a very thin endocardium, that was associated with less collagen and heightened MMP expression in the atria. During aging, we found that the expression of mRNAs for atrial MMP7, MMP8, and MMP9 peaked at 18 months, which closely correlated with reductions in collagen content and the time-window for cardioembolic stroke in these mice. Treatment of mice with an MMP inhibitor at 17-18 months of age reduced atrial inflammation and remodeling, and stroke incidence. Taken together, our study demonstrates that aging-induced LAA thrombus formation occurs through a mechanism involving upregulation of MMPs and breakdown of collagen, and that treatment with an MMP inhibitor may be effective as a treatment strategy for this heart condition.

The association between arterial stiffness and cancer occurrence: Data from Kailuan cohort study.

Background: This study aimed to investigate whether increased arterial stiffness, measured by brachial-ankle pulse wave velocity (baPWV) is associated with cancer. Materials and methods: A total of 45,627 Chinese adults underwent a baPWV examination. The participants were followed up from 1st January 2012 to 31st December 2018. Cox proportional hazards model was used to assess the association between the baPWV values and cancer. Results: During a total follow-up duration of 172,775.69 person-years, there were 553 new cases of cancer. The subjects in the highest baPWV group showed an increased risk of cancer when compared with the lowest baPWV group as confirmed by multivariate-adjusted hazard ratios (HR = 1.51, 95% CI = 1.14∼2.00) in the entire cohort. Compared with participants in the lowest baPWV group, the HRs (95% CI) for digestive cancer in the second and third groups were 1.55 (1.00∼2.40) and 1.99 (1.19∼3.33), respectively. The Kaplan-Meier analysis demonstrated a significant increase in cancer in participants with a baPWV ≥ 18 m/s (P < 0.001). Compared with the lowest baPWV group, the highest baPWV group showed an increased risk of cancer in men (HR = 1.72, 95% CI = 1.22∼2.43) and those < 60 years (HR = 1.75, 95% CI = 1.20∼2.55), respectively. Conclusion: Increased arterial stiffness measured by baPWV is associated with cancer occurrence, especially digestive cancer occurrence. Clinical trial registration: ClinicalTrials.gov, identifier ChiCTR-TNRC-11001489.

The predictive value of changes in left atrial volume index for rehospitalization in heart failure with preserved ejection fraction.

AIMS: Left atrial volume index (LAVI) is an adequate analysis to predicate the left ventricle (LV) filling pressures, providing a powerful predictive marker of LV diastolic dysfunction. LAVI is a dynamic morphophysiological marker, and whether LAVI changes can predicate clinical outcomes in HF with preserved ejection fraction (HFpEF) is unknown. METHODS: HFpEF patients were retrospectively studied from the First Affiliated Hospital of Dalian Medical University. Patients were classified into deteriorated, stable and improved groups according to the change in LAVI. Rehospitalization was defined as the main endpoint, the composite outcome of rehospitalization or all-cause death was defined as the secondary endpoint. RESULTS: A total of 409 patients were included. In this cohort, the percentage of deteriorated, stable, and improved LAVI were 99 (24.2%), 235 (57.4%), and 75 (18.4%), respectively. During the 22 months follow-up period, 168 patients (41.1%) were rehospitalized, 31 patients (7.5%) died and 182 patients (44.5%) experienced a composite outcome. Multivariate Cox regression showed that compared to improved LAVI, those with deteriorated and stable LAVI experienced higher risk of rehospitalization. Logistic regression showed atrial fibrillation (AF) and higher creatinine were independent predictors of deteriorated LAVI, whereas the use of loop diuretics, calcium channel blockers (CCB), and high level of high-density lipoprotein cholesterol (HDL-C) were significantly associated with improved LAVI. CONCLUSIONS: Change in LAVI provides a powerful and dynamic morphophysiological marker of LV filling status and can be used to evaluate the rehospitalization in HFpEF patients.

Hyperglycemia promotes myocardial dysfunction via the ERS-MAPK10 signaling pathway in db/db mice.

Recent studies have demonstrated that hyperglycemia is a major risk factor for the development and exacerbation of cardiovascular disease (CVD). However, the molecular mechanisms involved in diabetic cardiomyopathy (DCM) have not been fully elucidated. In this study, we focused on the underlying mechanism of DCM. Leptin receptor-deficient db/db mice were used to model a type 2 diabetes mellitus (T2DM) model in our study. WT mice and db/db mice received 4-phenylbutyric acid (4-PBA) (25 mg/kg/day) and saline by intraperitoneal injection every other day for 4 weeks. WT and db/db mice were given tail vein injections of 100 µL of rAAV9-Sh-MAPK10 and rAAV9-Sh-GFP at the age of 6-8 weeks. Echocardiography was performed to measure cardiac function, histological examinations were used to evaluate ventricular hypertrophy and fibrosis. Quantitative RT-qPCR was used to assess the mRNA expression of Jun N-terminal kinase 3 (JNK3, MAPK10), atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and collagen I and III. Immunoblotting was performed to measure the levels of cardiac hypertrophy-related proteins, fibrosis-related proteins, endoplasmic reticulum stress (ERS)-related proteins and apoptosis-related proteins. TUNEL staining was performed to examine cardiomyocyte apoptosis. In contrast to 12-week-old db/db mice, 16-week-old db/db mice showed the most severe myocardial dysfunction. The DCM induced by hyperglycemia was largely alleviated by 4-PBA (25 mg/kg/day, intraperitoneal injection). Similarly, tail vein injection of rAAV9-Sh-MAPK10 reversed the phenotype of the heart in db/db mice including cardiac hypertrophy and apoptosis in db/db mice. The mechanistic findings suggested that hyperglycemia initiated the ERS response through the negative regulation of sirtuin 1 (SIRT1), leading to the occurrence of myocardial dysfunction, and specific knockdown of MAPK10 in the heart directly reversed myocardial dysfunction induced by hyperglycemia. We demonstrated that hyperglycemia promotes DCM in db/db mice through the ERS-MAPK10 signaling pathway in diabetic mice.

Optimal Catheter Ablation Strategy for Patients with Persistent Atrial Fibrillation and Heart Failure: A Retrospective Study.

The optimal catheter ablation (CA) strategy for patients with persistent atrial fibrillation (PeAF) and heart failure (HF) remains uncertain. Between 2016 and 2020, 118 consecutive patients with PeAF and HF who underwent the CA procedure in two centers were retrospectively evaluated and divided into the pulmonary vein isolation (PVI)-only and PVI + additional ablation groups. Transthoracic echocardiography (TTE) was performed at baseline, one month, and 12 months after the CA procedure. The HF symptoms and left ventricular ejection fraction (LVEF) improvements were analyzed. Fifty-six patients underwent PVI only, and 62 patients received PVI with additional ablation. Compared with the baseline, a significant improvement in the LVEF and left atrial diameter postablation was observed in all patients. No significant HF improvement was detected in the PVI + additional ablation group than in the PVI-only group (74.2% vs. 71.4%, P = 0.736), but the procedure and ablation time were significantly longer (137.4 ± 7.5 vs. 123.1 ± 11.5 min, P = 0.001). There was no significant difference in the change in TTE parameters and the number of rehospitalizations. For patients with PeAF and HF, CA appears to improve left ventricular function. Additional ablation does not improve outcomes and has a significantly longer procedure time. Trial registration number is as follows: ChiCTR2100053745 (Chinese Clinical Trial Registry; https://www.chictr.org.cn/index.aspx).

Melatonin inhibits angiotensin II-induced atrial fibrillation through preventing degradation of Ang II Type I Receptor-Associated Protein (ATRAP).

Angiotensin II (Ang II) induced Atrial fibrillation (AF) often accompanied with reduced ATRAP which is a negative modulator of Ang II type 1 receptor (AT1R). Melatonin can protect against AF, but the underlying molecular mechanism remains poorly understood. In this study, Ang II was used to induce AF, and AF inducibility and duration were documented telemetrically. Ang II-infused mice had a higher AF incidence, which was associated with atrial fibrosis, inflammation, and oxidative stress. Melatonin partially inhibited these effects, and enforced expression of siRNA-ATRAP in atria counteracted the beneficial role of melatonin. Specifically, melatonin inhibited expression of Ang II-induced proteasome and immunoproteasome subunits ß2, ß2i, ß5, and ß5i as well as their corresponding trypsin-like and chymotrypsin-like activities and blocked ATRAP degradation. In turn, this inhibited AT1R-mediated NF-κB signaling, transforming growth factor (TGF)-ß1/Smad signaling in the atria, and thereby affected atrial remodeling and AF. Melatonin receptor inhibition by the chemical inhibitor luzindole partially inhibited the inhibitory effects of melatonin on proteasome activity and also Ang II-induced pathological changes in the atria. Overall, our study demonstrates that melatonin protects against Ang II-induced AF by inhibiting proteasome activity and stabilizing ATRAP expression, and these effects are partially dependent on melatonin receptor activation.

Short QRS Duration After His-Purkinje Conduction System Pacing Predicts Left Ventricular Complete Reverse Remodeling in Patients With True Left Bundle Branch Block and Heart Failure.

Objective: This study aimed to explore the outcomes of His-Purkinje conduction system pacing (HPCSP) and to screen the predictors of left ventricular (LV) complete reverse remodeling in patients with true left bundle branch block (LBBB) and heart failure with reduced ejection fraction (HFrEF). Methods: Patients who underwent HPCSP for true LBBB and HFrEF from April 2018 to August 2020 were consecutively enrolled. All participants were followed up for at least 1 year. Thrombosis, infection, lead dislodgement, perforation, and other complications were observed after HPCSP. Clinical data, including echocardiographic parameters, electrocardiogram measurements, and cardiac function, were assessed before and after the procedure. Results: A total of 46 patients were enrolled. HPCSP was successfully deployed in 42 cases (91.30%), which included 37 cases with His bundle pacing (HBP) and 5 cases with left bundle branch pacing (LBBP). The QRS duration decreased significantly (169.88 ± 19.17 ms vs. 113.67 ± 20.68 ms, P < 0.001). Left ventricular end-systolic volume (LVESV) (167.67 ± 73.20 ml vs. 85.97 ± 62.24 ml, P < 0.001), left ventricular end-diastolic diameter (LVEDD) (63.57 ± 8.19 mm vs. 55.46 ± 9.63 mm, P = 0.003) and left ventricular ejection fraction (LVEF) (26.52 ± 5.60% vs. 41.86 ± 11.56%, P < 0.001) improved dramatically. Complete reverse remodeling of the LV with normalized LVEF and LVEDD was found in nearly half of the patients (45.24%). A short QRS duration after HPCSP was a strong predictor of normalized LVEF and LVEDD (P < 0.001). The thresholds increased markedly in two patients approximately 6 months after HBP. No patients died during the total follow-up period of 20.07 ± 6.45 months. Conclusion: Complete reverse remodeling of the LV could be found in nearly half of the patients with HFrEF and true LBBB after HPCSP, and the short QRS duration after HPCSP was a strong predictor.

A Retrospective Study of the Relationship Between the Triglyceride Glucose Index and Myocardial Revascularization for New-Onset Acute Coronary Syndromes.

Background: This study explored the relationship between the TyG index/serum uric acid (SUA) panel and myocardial revascularization (MRT) for new-onset acute coronary syndromes (ACS). Methods: Between January 2011 and July 2020, 13,271 new-onset ACS patients were enrolled. The logistic regression models and the odds ratios (ORs) were used to quantify the risk of TyG index/SUA and MRT. Then, interaction analyses of TyG index and SUA on MRT were applied. Results: Elevated TyG index was positively associated higher risks of MRT. However, SUA levels were negatively associated with MRT. Compared with those in the lowest quartile, the risk of MRT increased gradually among patients in Q1 of the SUA category (OR = 1.03, 1.11, and 1.28 for Q2, Q3, and Q4 of TyG index, respectively), Q2 of the SUA category (OR = 1.41, 1.68, and 2.18 for Q2, Q3, and Q4 of TyG index, respectively), Q3 of the SUA category (OR = 1.05, 1.45, and 1.45 for Q2, Q3, and Q4 of TyG index, respectively), and Q4 of the SUA category (OR = 1.20, 1.29, and 1.46 for Q2, Q3, and Q4 of TyG index, respectively). This pattern was observed in both male and female, as well as patients without type 2 diabetes mellitus. Conclusion: Patients with a higher TyG index have a higher proportion of MRT in new-onset ACS. This result also applies to patients with different levels of SUA during new-onset ACS.

Anthracycline-Induced Atrial Structural and Electrical Remodeling Characterizes Early Cardiotoxicity and Contributes to Atrial Conductive Instability and Dysfunction.

Aims: Cancer patients treated with anthracyclines are susceptible to atrial fibrillation (AF), while the mechanisms remain unclear. Due to sudden and unpredictable features, prediction of anthracycline-induced AF at early phase is difficult. Clinically, we tested whether anthracycline-induced early atrial remodeling in patients could be detected by echocardiography. Experimentally, we investigated the mechanisms of doxorubicin-induced atrial remodeling and AF in mice, and the protective effects of dexrazoxane and antioxidants. Methods and Results: Postsurgery breast cancer patients with an anthracycline-containing or anthracycline exclusion regimen were recruited for echocardiography before chemotherapy, and 3 and 6 months after chemotherapy. Mice were injected with doxorubicin or vehicle (5 mg/kg/week, 4 weeks), and left atrial diameter, electrical transmission, and AF inducibility were measured. Meanwhile, the level of reactive oxygen species (ROS), activity of antioxidant enzymes, cardiomyocyte size, vacuolization, inflammation, and fibrosis were also measured in mouse atria. The therapeutic effects of dexrazoxane and antioxidants on doxorubicin-induced changes in the aforementioned parameters were also determined. While ventricular parameters and functions were unchanged in cancer patients receiving anthracyclines before and after chemotherapy, left atrial reservoir and conduit function were decreased at 3 months postchemotherapy versus prechemotherapy. Doxorubicin-induced susceptibility to AF occurred in mice before onset of ventricular dysfunction. Doxorubicin-induced AF was via inducing structural remodeling (cardiomyocyte death, hypotrophy, and vacuolization) and electrical remodeling (reduction and redistribution of connexin 43) in atria, which was effectively prevented by dexrazoxane or antioxidants through inhibiting ROS generation or enhancing ROS elimination. Innovation and Conclusion: AF inducibility was induced after doxorubicin injection, which can be inhibited by repressing the ROS level. Antioxid. Redox Signal. 37, 19-39. The Clinical Trial Registration number is PJ-KS-KY-2019-73.

Research progress on the role of ferroptosis in cardiovascular disease.

The cardiovascular disease pathogenesis is extremely complex and seriously threatens human health. Cardiomyocyte death plays a significant role in cardiovascular disease occurrence and development. In addition to the previously revealed modes of cell death (apoptosis, autophagy, and pyroptosis), ferroptosis is highly related to the development of cardiovascular diseases, including arrhythmia, atherosclerosis, and myocardial ischemia/reperfusion. Ferroptosis is a novel cell death pathway driven by lipid peroxidation and iron overload. Lipid, amino acid, and iron metabolism regulate the ferroptosis pathway. Small molecule compounds (iron chelators, antioxidants, and ferroptosis inhibitors) and genetic programming can alleviate or prevent cardiovascular disease by inhibiting the ferroptosis pathway. Ferroptosis plays a key role in various cardiovascular disease occurrence and development, and inhibiting ferroptosis in cardiomyocytes is expected to become a feasible treatment method. In this mini-review, we systematically summarize the molecular mechanisms of ferroptosis in different cardiovascular diseases, delineate the regulatory network between ferroptosis and cardiovascular diseases, and highlight its potential therapeutic targets.

Circulating Soluble Suppression of Tumorigenicity 2 Predicts Recurrence After Radiofrequency Ablation of Persistent Atrial Fibrillation.

Objective: A more extensively fibrotic left atrium contributes to atrial fibrillation (AF) occurrence, persistence, and recurrence. The soluble suppression of tumorigenicity 2 (sST2) has emerged as a ventricular fibrotic biomarker for patients with heart failure. The present study is to investigate associations between circulating sST2 and risk of recurrence after ablation in AF patients. Methods: We measured the baseline plasma level of sST2 from patients with persistent AF (n = 117) and paroxysmal AF (n = 93) patients. Patients were followed up for 15 months after ablation. The relationship between circulating sST2 and recurrence was assessed by multivariable Cox regression. The cutoff value of sST2 was determined by receiver operating characteristic curve. The relationship between baseline sST2 level and left atrial volume index (LAVI) was assessed by multivariate linear regression analysis. Serial sST2 measurements were also conducted after 24 h, 6 months, and 15 months of ablation. ST2 localization was examined in left atrial appendages of persistent AF patients by immunohistochemistry and Western blot. Results: Baseline sST2 positively associated with LAVI in the persistent AF group, and elevated sST2 (≥39.25 ng/ml) independently increased the risk of recurrence after ablation (area under the curve = 0.748), with hazard ratio of 1.038 (95% confidence interval 1.017-1.060, P < 0.001) when adjusted for co-variables. In contrast, elevated sST2 cannot predict recurrence in paroxysmal AF. Conclusions: In persistent AF patients, increased sST2 serves as a marker of recurrence after radiofrequency ablation. Patients with sST2 ≥ 39.25 ng/ml are more likely to develop recurrence within a year.

Brady-arrhythmias in patients with atrial fibrillation and heart failure of reduced ejection fraction: is his-bundle pacing superior to biventricular pacing？.

OBJECTIVE: To investigate the efficacy and safety of His-bundle pacing (HBP) compared with the traditional biventricular pacing (BVP) on patients with brady-arrhythmias, who suffer from permanent atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). METHODS: All patients with brady-arrhythmias, permanent AF and HFrEF were continuously enrolled from January 2017 to July 2019 and followed up for at least 12 months. The differences in QRS duration (QRSd), New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF), tricuspid regurgitation grade, mitral regurgitation grade, left ventricular end-diastolic diameter (LVEDD), and left atrial size were compared. RESULTS: A total of 52 patients were enrolled: 37 patients were with HBP and 15 patients with BVP. There was no electrode dislodged, perforation, infection or thrombosis during the follow-up of 18.12 ± 4.45 months. The success rate for HBP implantation was 88.10%. The capture threshold of his-bundle and the threshold of the left ventricular lead remained stable during follow-up. LVEF increased to higher than 50% in 11 patients with HBP (29.73%). The NYHA classification (both p < .001), LVEF (both p < .001) and LVEDD improved significantly during the follow-up in both groups. NYHA (p = .030), LVEF (p = .013), and LVEDD (p = .003) improved in patients with HBP compared with BVP. CONCLUSION: HBP was safe and more effective in improving the cardiac function and remodeling in patients with brady-arrhythmias, permanent AF and HFrEF compared with BVP.

Appropriate intraprocedural initial heparin dosing in patients undergoing catheter ablation for atrial fibrillation receiving uninterrupted non-vitamin-K antagonist oral anticoagulant treatment.

BACKGROUND: To clarify the appropriate initial dosage of heparin during radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF) receiving uninterrupted nonvitamin K antagonist oral anticoagulant (NOAC) treatment. METHODS: A total of 187 consecutive AF patients who underwent their first RFCA in our center were included. In the warfarin group (WG), an initial heparin dose of 100 U/kg was administered (control group: n = 38). The patients who were on NOACs were randomly divided into 3 NOAC groups (NG: n = 149), NG110, NG120, and NG130, and were administered initial heparin doses of 110 U/kg, 120 U/kg, and 130 U/kg, respectively. During RFCA, the activated clotting time (ACT) was measured every 15 min, and the target ACT was maintained at 250-350 s by intermittent heparin infusion. The baseline ACT and ACTs at each 15-min interval, the average percentage of measurements at the target ACT, and the incidence of periprocedural bleeding and thromboembolic complications were recorded and analyzed. RESULTS: There was no significant difference in sex, age, weight, or baseline ACT among the four groups. The 15 min-ACT, 30 min-ACT, and 45 min-ACT were significantly longer in the WG than in NG110 and NG120. However, no significant difference in 60 min-ACT or 75 min-ACT was detected. The average percentages of measurements at the target ACT in NG120 (82.2 ± 23.6%) and NG130 (84.8 ± 23.7%) were remarkably higher than those in the WG (63.4 ± 36.2%, p = 0.007, 0.003, respectively). These differences were independent of the type of NOAC. The proportion of ACTs in 300-350 s in NG130 was higher than in WG (32.4 ± 31.8 vs. 34.7 ± 30.6, p = 0.735). Severe periprocedural thromboembolic and bleeding complications were not observed. CONCLUSIONS: For patients with AF receiving uninterrupted NOAC treatment who underwent RFCA, an initial heparin dosage of 120 U/kg or 130 U/kg can provide an adequate intraprocedural anticoagulant effect, and 130 U/kg allowed ACT to reach the target earlier. TRIAL REGISTRATION: Registration number: ChiCTR1800016491, First Registration Date: 04/06/2018 (Chinese Clinical Trial Registry http://www.chictr.org.cn/index.aspx ).