刘尚雨
中国医学科学院阜外医院 心律失常中心
BACKGROUND:Autoimmune myocarditis, with increasing incidence and limited therapeutic strategies, is in urgent need to explore its underlying mechanisms and effective drugs. Pyroptosis is a programmed cell death that may contribute to the pathogenesis of myocarditis. Nonetheless, no direct evidence validated the role of pyroptosis in autoimmune myocarditis. Lupeol (Lup), a pentacyclic triterpene, possesses various biological activities such as antidiabetic properties. However, the effects of Lup on autoimmune myocarditis and pyroptosis remain unelucidated.PURPOSE:This study aimed to reveal the role of pyroptosis in autoimmune myocarditis and explore the protective effects of Lup, and its engaged mechanisms.METHODS:The experimental autoimmune myocarditis (EAM) mouse model was established by immunization with a fragment of cardiac myosin in Balb/c mice. Lup and MCC950 were administered after EAM induction. The protective effects were assessed by inflammation score, cardiac injury, chronic fibrosis, and cardiac function. Mechanistically, the effects of Lup on the M1 polarization and pyroptosis of macrophages were evaluated. Transcriptome sequencing and molecular docking were subsequently employed, and the underlying mechanisms of Lup were further explored in vitro with small interfering RNA and adenovirus.RESULTS:Administration of Lup and MCC950 alleviated EAM progression. Western blotting and immunofluorescence staining identified macrophages as the primary cells undergoing pyroptosis. Lup inhibited the expression of pyroptosis-associated proteins in macrophages during EAM in a dose-dependent manner. Furthermore, Lup suppressed pyroptosis in both bone marrow-derived macrophages (BMDMs) and THP-1-derived macrophages in vitro. In addition, Lup inhibited the M1 polarization of macrophages both in vivo and in vitro. Mechanistically, the protective effects of Lup were demonstrated via the suppression of the nuclear factor-κΒ (NF-κB) signaling pathway. Transcriptome sequencing and molecular docking revealed the potential involvement of peroxisome proliferator-associated receptor α (PPARα). Subsequently, we demonstrated that Lup activated PPARα to reduce the expression level of LACC1, thereby inhibiting the NF-κB pathway and pyroptosis.CONCLUSION:Our findings indicated the crucial role of macrophage pyroptosis in the pathogenesis of EAM. Lup ameliorated EAM by inhibiting the M1 polarization and pyroptosis of macrophages through the PPARα/LACC1/NF-κB signaling pathway. Thus, our results provided a novel therapeutic target and agent for myocarditis.
Phytomedicine : international journal of phytotherapy and phytopharmacology 2024
AIMS:Catheter ablation of ventricular tachycardia (VT) improves VT-free survival in 'classic' arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to investigate electrophysiological features and ablation outcomes in patients with ARVC and biventricular (BiV) involvement.METHODS AND RESULTS:We assembled a retrospective cohort of definite ARVC cases with sustained VTs. Patients were divided into the BiV (BiV involvement) group and the right ventricular (RV) (isolated RV involvement) group based on the left ventricular systolic function detected by cardiac magnetic resonance. All patients underwent electrophysiological mapping and VT ablation. Acute complete success was non-inducibility of any sustained VT, and the primary endpoint was VT recurrence. Ninety-eight patients (36 ± 14 years; 87% male) were enrolled, including 50 in the BiV group and 48 in the RV group. Biventricular involvement was associated with faster clinical VTs, a higher VT inducibility, and more extensive arrhythmogenic substrates (all P < 0.05). Left-sided VTs were observed in 20% of the BiV group cases and correlated with significantly reduced left ventricular systolic function. Catheter ablation achieved similar acute efficacy between these two groups, whereas the presence of left-sided VTs increased acute ablation failure (40 vs. 5%, P = 0.012). Over 51 ± 34 months [median, 48 (22-83) months] of follow-up, cumulative VT-free survival was 52% in the BiV group and 58% in the RV group (P = 0.353). A multivariate analysis showed that younger age, lower RV ejection fraction (RVEF), and non-acute complete ablation success were associated with VT recurrence in the BiV group.CONCLUSION:Biventricular involvement implied a worse arrhythmic phenotype and increased the risk of left-sided VTs, while catheter ablation maintained its efficacy for VT control in this population. Younger age, lower RVEF, and non-acute complete success predicted VT recurrence after ablation.
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2024
BACKGROUND:Renal denervation (RDN) is a promising treatment based on catheter intervention for patients with refractory hypertension. However, the effect in patients with isolated systolic hypertension (ISH) remains controversial. The aim of this meta-analysis was to determine the blood pressure lowing effect of RDN in patients with ISH compared with combined systolic/diastolic hypertension (CH) patients.METHODS:PubMed, Embase, Cochrane and ClinicalTrials.gov were searched for prospective clinical studies that included RDN. The outcomes of interest were the change of 24-hour ambulatory systolic blood pressure (SBP) from baseline. We used the fixed effects model to calculate weighted mean difference (WMD) with 95% confidence interval (CI).RESULTS:Six trials were included, with 1405 participants, including 597 patients with ISH and 808 patients with CH. Mean follow-up was five months. The reduction of 24-hour ambulatory SBP was significantly greater for the CH patients than the ISH patients (WMD = 3.89, 95% CI: 2.32-5.45, P < 0.0001). RDN also showed a greater reduction in office SBP in the CH patients compared to the ISH patients (WMD = 10.24, 95% CI: 4.24-15.74, P = 0.0003). And the effect was independent of age, length of follow-up, and ablation device.CONCLUSIONS:RDN provides superior blood pressure control in the CH patients compared with the ISH patients, and the CH patients may be the best suitable population for which RDN is indicated.
Journal of geriatric cardiology : JGC 2023
BACKGROUND:Catheter ablation of premature ventricular contractions (PVCs) that trigger polymorphic ventricular tachycardia (PVT) or ventricular fibrillation has been reported as a novel therapy to reduce the syncope events in patients with catecholaminergic PVT, whereas the long-term ablation outcome and its value in improving exercise-induced ventricular arrhythmias remain unclear.METHODS AND RESULTS:Fourteen consecutive selected patients with catecholaminergic PVT (mean±SD age, 16±6 years; 43% male patients) treated with maximum β-blockers with no possibility of adding flecainide were prospectively enrolled for catheter ablation. The primary end point was syncope recurrence, and the secondary end point was the reduction of the ventricular arrhythmia score during exercise testing. Twenty-six PVT/ventricular fibrillation-triggering PVCs were identified for ablation. The trigger beats arose from the left ventricle in 50% of the cases and from both ventricles in 36% of the cases. Purkinje potentials were observed at 27% of the targets. After a mean follow-up of 49 months after ablation, 8 (57%) patients were free from syncope recurrence. Ablation of trigger beat significantly reduced the syncope frequency (mean±SD, 4.3±1.6 to 0.5±0.8 events per year; P<0.001) and improved the ventricular arrhythmia scores at the 3-month (5 [range, 3-6] to 1.5 [range, 0-5]; P=0.002) and 12-month (5 [range, 3-6] to 2 [range, 0-5]; P=0.014) follow-ups. The induction of nontriggering PVCs postablation was closely associated with syncope recurrence (hazard ratio, 6.8 [95% CI, 1.3-35.5]; P=0.026).CONCLUSIONS:Catheter ablation of PVT/ventricular fibrillation-triggering PVCs in patients with catecholaminergic PVT who cannot receive flecainide treatment seems to be a safe and feasible adjunctive treatment that may reduce the syncope burden and improve exercise-related ventricular arrhythmias. Induction of nontriggering PVCs after ablation is associated with a higher risk of syncope recurrence.
Journal of the American Heart Association 2023
BACKGROUND:Female patients are underrepresented in randomized controlled clinical trials and registries of ventricular arrhythmia (VA). Personalized prevention and therapies require an understanding of sex differences in risk factors and prognosis of VA.OBJECTIVE:We aimed to assess sex differences in the incidence, risk factors, and mortality of VA in congestive heart failure (HF) patients.METHODS:This study included 10,889 patients (mean [SD] age, 73.8 [13.4] years; 5917 [53.8%] male) with congestive HF, of which 1555 (14.3%) patients developed VA during hospitalization. VA incidence, potential risk factors, and in-hospital mortality were evaluated in both sexes.RESULTS:Men were more strongly associated with incident VA compared with women (odds ratio [OR]: 2.006, 95% CI: 1.790-2.248, p < 0.001). Thirteen potential predictors, which accounted for 91.0% of the risk of VA in men and 88.2% in women, were included in this study. There were significant interactions by sex in the association between incident VA, atrial fibrillation (AF) (relative risk ratio = 0.730, 95% CI: 0.571-0.933, interaction p = 0.012), and non-ischemic cardiomyopathy (NICM) (relative risk ratio = 1.391, 95% CI: 1.029-1.872, interaction p = 0.030). Congestive HF patients developed with VA had an approximately 1.5-fold risk of in-hospital mortality, which was not affected by sex.CONCLUSIONS:In congestive HF patients, incident VA was an independent risk factor of in-hospital mortality, and male sex was strongly associated with an increased risk of VA. Awareness of sex differences in the association of AF and NICM with VA may enhance therapeutic decisions, thus improving their clinical outcomes.
International journal of cardiology 2023
BACKGROUND:Intracardiac echocardiography (ICE) provides accurate left atrial (LA) anatomical information in the procedure of atrial fibrillation (AF) ablation but lacks LA functional assessment. LA reservoir strain (LASr) is an excellent marker of LA reservoir function. This study aimed to assess the agreement between LASr derived from ICE and transthoracic echocardiography (TTE) in AF patients and analyze the reproducibility of LASr assessed by ICE combined with speckle tracking imaging.METHODS:This study prospectively enrolled 110 patients with a clinical diagnosis of AF who were ready for AF ablation, including 71 patients with paroxysmal AF and 39 with persistent AF. TTE and ICE examinations were performed on each individual before AF ablation. LASr measurements derived from ICE and TTE images were using dedicated LA-tracking software. Pearson correlation coefficients (r) and Bland-Altman plots were used to evaluate the agreement of LASr between the two modalities. Intraclass correlation coefficients (ICCs) were used to assess intra- and inter-observer reproducibility.RESULTS:The agreement between LASr obtained from ICE and TTE, especially between LASrLPV (LASr derived from LA left pulmonary vein view of ICE) and LASrTTE (LASr derived from TTE) were good in both paroxysmal and persistent AF patients [r = 0.890 (P < 0.001) for overall population; r = 0.815 (P < 0.001) and Bias ± LOA: -0.3 ± 9.9% for paroxysmal AF; r = 0.775 (P < 0.001) and Bias ± LOA: -2.6 ± 3.9% for persistent AF, respectively]. But the values of LASr derived from ICE were slightly lower than those of TTE, especially in patients with persistent AF. The ICCs for LASr derived from ICE were excellent (all ICCs > 0.90).CONCLUSIONS:In patients with AF, LASr derived from ICE demonstrated excellent reproducibility and showed good agreement with LASr obtained from TTE. Obtaining LASr from ICE images may be a supplementary method to evaluate LA reservoir function in AF patients and expands the potential of ICE in the field of cardiac function assessment.
Cardiovascular ultrasound 2023
BACKGROUND:Cardioneuroablation is an emerging therapy for refractory vasovagal syncope (VVS), but the standard enrollment criterion is undetermined. Mainstream studies empirically enroll patients with cardioinhibitory and mixed types of VVS on the basis of the head-up tilt (HUT). However, a variety of studies have shown that the results of HUT exhibit unpleasant reproducibility.OBJECTIVE:We aimed to investigate the prognostic value of baseline deceleration capacity in patients with refractory VVS after cardioneuroablation.METHODS:This study enrolled 123 patients (mean age 42.2±17.7 years; 54 males [43.9%]) with the diagnosis of VVS, of whom 16 patients had a negative result of HUT (13.0%), 8 (6.5%) had vasodepressive VVS, 32 (26.0%) cardioinhibitory VVS, and 67 (54.5%) mixed VVS. All patients underwent cardioneuroablation that was performed in the left atrium.RESULTS:After a mean follow-up of 4.0±1.1 years, 33 patients experienced syncope/presyncope events (26.8%). Patients with recurrent syncope/presyncope have a lower baseline deceleration capacity level than do those without (8.9±3.2 ms vs 11.3±3.7 ms; P < .001). Each 1-ms increase in deceleration capacity had a 34% (95% confidence interval [CI] 12%-50%) reduced risk of syncope/presyncope recurrence after cardioneuroablation. Nighttime deceleration capacity had the highest discrimination value (area under the curve 0.757; 95% confidence interval 0.657-0.858). At a high-risk threshold of 51% (nighttime deceleration capacity at a cutoff of 9.9 ms), the nighttime deceleration capacity enrollment strategy additionally benefited 18 per 100 patients after cardioneuroablation without syncope/presyncope recurrence as compared with the HUT strategy in decision curve analyses.CONCLUSION:Baseline nighttime deceleration capacity ≥ 10 ms may act as an indication for cardioneuroablation in patients with refractory VVS.
Heart rhythm 2022
Backgrounds:Decreased urine output (UO) is associated with adverse outcomes in certain patients, but this effect in patients admitted for cardiovascular diseases is still unproven. Moreover, the relationship between increased UO and prognosis is also unclear.Objective:To investigate the relationship between decreased or increased UO and outcomes in patients with the cardiovascular intensive care unit (CICU).Methods:This study was a retrospective cohort analysis based on the medical information mart for intensive care III (MIMIC-III) database. The patients' data were extracted from the Beth Israel Deaconess Medical Center (Boston, MA) between 2001 and 2012. With the initial 24-h UO range from 0.5 to 1.0 ml/kg/h as the reference, participants were divided into the several groups. The primary outcome was 30-day mortality. The secondary outcomes were 90-day mortality, ICU mortality, hospital mortality, use of mechanical ventilation (MV), and vasopressor agents in the first 24-h of ICU. The association between UO and mortality was assessed by multivariable logistic regression.Results:A total of 13,279 patients admitted to CICU were included. Low UO (< 0.5 ml/kg/h) was strongly associated with 30-day mortality (unadjusted OR = 3.993, 95% CI: 3.447-4.625, p < 0.001), and very high UO (≥ 2.0 ml/kg/h) was also a significantly risk factor for 30-day mortality (Unadjusted OR = 2.069, 95% CI: 1.701-2.516, p < 0.001) compared with the reference. The same effects also were shown in the multivariable logistic regression, adjusted by age, gender, vital signs, common comorbidities, and use of diuretics, with an adjusted OR of 2.023 (95% CI: 1.693-2.417, p < 0.001) for low UO and 1.771 (95% CI: 1.389-2.256, p < 0.001) for very high UO. Moreover, both decreased UO and increased UO were risk factors for 90-day mortality, ICU mortality, hospital mortality, use of MV and vasopressor agents.Conclusion:The decreased and increased UO both were significantly associated with short-term mortality, the relationship between UO and mortality was U-shape rather than linear.
Frontiers in cardiovascular medicine 2022
BACKGROUND:Mechanically ventilated patients with congestive heart failure (CHF) are at high-risk of mortality. We aimed to develop and validate a prediction model based on machine learning (ML) algorithms to predict hospital mortality in mechanically ventilated patients with CHF.METHODS:Least absolute shrinkage and selection operator (LASSO) regression was used to identify the key features. Hyperparameters optimization (HPO) was conducted to modify the prediction model. The area under the receiver operating characteristic curve (AUC), accuracy, calibration curve and decision curve analysis were used to evaluate prediction performance. The final model was validated using an external validation set from another database. The prediction results were represented by a nomogram.RESULTS:A total of 4530 qualified patients were included. Among 11 ML-algorithms, CatBoost showed the best prediction performance (AUC = 0.833). And 10 key features (10/63) were selected based on the LASSO regression. After HPO, the prediction performance of the CatBoost model based on the key features was significantly improved (AUCs: 0.805 vs. 0.821). Additionally, the CatBoost model also showed the satisfactory prediction performance in the external validation set (AUC = 0.806).CONCLUSION:The present study developed and validated a CatBoost model, which could accurately predict hospital mortality in mechanically ventilated patients with CHF.
International journal of cardiology 2022
BACKGROUND:Mechanical ventilation (MV) is widely used to relieve respiratory failure in patients with congestive heart failure (CHF). Prolonged MV (PMV) is associated with a poor prognosis. We aimed to establish a prediction model based on machine learning (ML) algorithms for the early identification of patients with CHF requiring PMV.METHODS:Twelve commonly used ML algorithms were used to build the prediction model. The least absolute shrinkage and selection operator (LASSO) regression was employed to select the key features. We examined the area under the curve (AUC) statistics to evaluate the prediction performance. Data from another database were used to conduct external validation.RESULTS:We screened out 10 key features from the initial 65 variables via LASSO regression to improve the practicability of the model. The CatBoost model showed the best performance for predicting PMV among the 12 commonly used ML algorithms, with favorable discrimination (AUC = 0.790) and calibration (Brier score = 0.154). Moreover, hospital mortality could be accurately predicted using the CatBoost model as well (AUC = 0.844). In the external validation, the CatBoost model also showed satisfactory prediction performance (AUC = 0.780), suggesting certain generalizability of the model. Finally, a nomogram with risk classification of PMV was shown in this study.CONCLUSION:The present study developed and validated a CatBoost model, which could accurately predict PMV in mechanically ventilated patients with CHF. Moreover, this model has a favorable performance in predicting hospital mortality in these patients.
Cardiovascular drugs and therapy 2022
