Chronic intermittent hypoxia (CIH) is the predominant pathophysiological disorder of obstructive sleep apnea (OSA), known to be an important risk factor for atrial fibrillation (AF). MicroRNA-10b-5p levels are significantly reduced under hypoxic conditions. Nevertheless, the role and underlying mechanism of miR-10b-5p in CIH-induced AF remain elusive. In this study, we found that miR-10b-5p expression was downregulated in the atrial tissues of patients and rats with AF. Functionally, miR-10b-5p exerts protective roles in CIH induced atrial fibroblasts activation and AF development by inhibiting the expression of Smad ubiquitin regulatory factor 1 (SMURF1) and TGFβ/Smads signaling activation. RNA sequencing and bioinformatics identified that circ_Mkrn2, as possessing multiple putative binding sites for miR-10b-5p, was increased in patients and rats with AF. Circ_Mkrn2 overexpression promoted SMURF1 expression and atrial fibroblast activation, which were effectively reversed by miR-10b-5p overexpression. Circ_Mkrn2 silencing alleviated the expression of SMURF1 and TGFβ/Smads signaling activation, atrial fibroblasts activation and AF induced by CIH. Our findings showed that circ_Mkrn2 serves as an miR-10b-5p sponge,promotes Smurf1 expression, regulates atrial fibroblast activation, cardiac fibrosis and the development of AF, revealing a potential new target for the prevention of CIH-induced AF.
BACKGROUND:Despite increased risk of ischemic events in diabetes, the optimal anti-thrombotic strategy for secondary prevention has not been defined. We aimed to assess the efficacy and safety of optimal antiplatelet agents such as indobufen-based dual antiplatelet therapy (DAPT) in patients with diabetes after coronary stenting. METHODS:OPTION trial was a randomized, open-label, noninferiority, and multicentric study in China. Enrolled subjects were randomized 1:1 to indobufen-based DAPT or aspirin-based DAPT. This post hoc analysis from OPTION trial was performed by the presence of diabetes. The primary endpoint was a 1-year composite of cardiovascular death, nonfatal myocardial infarction, ischemic stroke, definite or probable stent thrombosis, or Bleeding Academic Research Consortium (BARC) criteria type 2, 3, or 5 bleeding. RESULTS:Of 4551 OPTION patients, the primary endpoint occurred in 93/1570 patients with diabetes (5.92%), as compared to 148/2981 without diabetes (4.96%) (HR: 0.72, 95% CI: 0.47-1.08, and HR: 0.73, 95% CI: 0.53-1.01, respectively), without significant interaction between diabetes status and treatment effect (Pinteraction = 0.935). The secondary efficacy endpoint was comparable between patients with (HR: 1.31, 95% CI: 0.60-2.84) and without diabetes (HR: 0.95, 95% CI: 0.51-1.76) (Pinteraction = 0.526). Similarly, both subgroups derived similar benefits for the safety endpoint (HR, 0.56; 95% CI, 0.34-0.92 for subjects with diabetes vs. HR, 0.66; 95% CI, 0.45-0.98 for those without diabetes; Pinteraction = 0.609). CONCLUSIONS:In patients receiving DES implantation, indobufen-based DAPT might be considered as a reasonable alternative to aspirin-based DAPT in the secondary prevention for those with diabetes, especially in patients at high bleeding risk.
Background: Chronic inflammation critically influences atherosclerotic progression and plaque destabilization. This investigation assessed and compared six lymphocyte-derived inflammatory indices (neutrophil-to-lymphocyte ratio (NLR), monocyte–lymphocyte ratio (MLR), platelet–lymphocyte ratio (PLR), systemic immune–inflammation index (SII), systemic inflammatory response index (SIRI), systemic immune–inflammation response index (SIIRI)) for predicting major adverse cardiovascular events (MACEs) in treatment-naïve acute coronary syndrome (ACS) patients undergoing coronary angiography. Methods: This study enrolled 1120 patients with newly diagnosed ACS, in which the occurrence of MACEs was monitored. The predictive capacities of the included lymphocyte-derived inflammatory indices were evaluated through receiver operator characteristic (ROC) curve analysis with optimal cutoffs, supplemented by Cox proportional hazards modeling. Results: A total of 265 MACEs (23.66%) were recorded during the 64.20 ± 23.05-month follow-up. Multivariate Cox analyses identified an elevated MLR (hazard ratio (HR) = 2.880, 95% confidence interval (CI) 1.280–6.470; p < 0.001) that was independently associated with the occurrence of MACEs in patients with newly diagnosed ACS. The ROC comparisons revealed a superior discriminative capacity of the MLR versus clinical factors, with an optimal MLR cutoff at 0.304 (sensitivity 61.1%; specificity 78.8%). Patients with a high MLR (≥0.304) exhibited a 3.5-fold increased risk of MACEs compared to those with a low MLR (46.96% vs. 13.29%; risk ratio = 1.635, 95% CI 1.475–1.812; p < 0.001); these data were corroborated by divergent Kaplan–Meier curves (log-rank p < 0.001). Meanwhile, subgroup analyses confirmed the prognostic consistency of the MLR across high-risk populations (age >60 years, diabetes, hypertension), with elevated MLR subgroups demonstrating uniformly higher rates of MACEs (all p < 0.001). Conclusions: MLR outperformed conventional parameters and five novel lymphocyte-based inflammatory indices in predicting MACEs in ACS patients; thus, the MLR can be established as a robust predictive biomarker. The clinical utility of the MLR extends to risk stratification across key patient subgroups, suggesting potential integration into routine cardiovascular risk assessment protocols.
BACKGROUND:Previous studies showed that doxycycline (Dox) can attenuate chronic intermittent hypoxia (CIH)-induced atrial fibrosis in rats. On this basis, we further investigated the effects of Dox on CIH-induced atrial electrical remodelling. METHODS:Rats were randomised into 3 groups: Control group, CIH group, and CIH with Dox treatment (CIH-D) group (n = 30). CIH and CIH-D rats were subjected to CIH 8 h/d for 6 weeks. After collecting the basic parameters of the rats, atrial fibrillation (AF) inducibility, conduction inhomogeneity, and epicardial conduction velocity were examined by in vitro cardiac electrophysiology experiments. The expression levels of ion channel subunits in the atrium were detected by Western blotting. Whole-cell patch clamp experiments were used to recorded action potential (AP), ICa-L, Ito, and the kinetic parameters. RESULTS:Compared to the Control rats, CIH rats showed increased AF inducibility, conduction inhomogeneity, and expression levels of p-RyR2, p-CaMKII, Kv11.1, Kir2.3, KCa3.1, whereas the epicardial conduction velocity, ICa-L, Ito, and expression levels of Cav1.2, Kv1.5, Kv4.3 were decreased. Dox-treatment significantly improved the expression levels of Kv1.5, Kv4.3 and Kir2.3 in CIH-D rats. CONCLUSION:CIH caused atrial electrical remodelling in our rats, which was improved by Dox treatment. These changes indicated the potential effects of Dox in AF.
BACKGROUND:Cardiac syncope can be life-threatening, but there is no clinical tool for initial screening. The study explored and developed optimal artificial intelligence methods for automatic diagnosis of cardiac syncope based on combinations of electrocardiogram parameters and clinical characteristics. METHODS:The patients presenting with syncope and hospitalized between June 21, 2018 and August 23, 2022 at the Second Hospital of Tianjin Medical University. The patients enrolled were divided into development cohort who were then randomly split into a training set and an internal validation set (4: 1) and temporal validation cohort. Fifteen features of syncope patients were ranked and valuable features were selected. Six supervised machine learning models were developed to explore a potential prediction model for cardiac syncope. The area under the curve (AUC) was the primary metric used to evaluate classification performance. RESULTS:A total of 380 patients (340 in the development cohort and 40 in the temporal validation cohort) were included in the final analysis. The random forest showed the best performance using the top twelve features ranked by importance, demonstrating an AUC of 0.85 (sensitivity: 0.72, specificity: 0.85, F1 score: 0.74) in the development cohort, and an AUC of 0.75 (sensitivity: 0.70, specificity: 0.65, F1 score: 0.68) in the validation cohort. The novel approach for automatic diagnosis of cardiac syncope has been proposed as web service for further application. CONCLUSIONS:Artificial intelligence methods may assist in syncope classification, and which have the potential to serve as a cost-effective and efficient screening tool for cardiac syncope.
Background It remains unclear whether indobufen-based dual antiplatelet therapy (DAPT) preserves ischemic protection while limiting bleeding risk in patients with multivessel coronary disease (MVD). This study aimed to investigate the efficacy and safety of indobufen-based DAPT in patients with MVD. Methods Patients in the OPTION trial were stratified based on the presence of MVD. We compared the ischemic and bleeding risks of indobufen-based DAPT (indobufen 100mg twice a day plus clopidogrel 75 mg/d for 12 months) vs conventional DAPT (aspirin 100 mg/d plus clopidogrel 75 mg/d for 12 months) in patients with and without MVD, using landmarks at 6 months and 1-year post-percutaneous coronary intervention (PCI). Results Patients with MVD tended to be older and contained a higher prevalence of high-risk features. Compared with patients without MVD, those with MVD were at higher risk for net adverse clinical events and ischemic events. The risk of ischemic events between indobufen-based DAPT vs conventional DAPT was similar either in patients with MVD or without MVD during the first and second 6 months. During the first 6 months, indobufen-based DAPT decreased the risk of bleeding events consistently in patients with and without MVD. Of note, during the second 6 months, indobufen-based DAPT continually decreased the risk of bleeding events in patients with MVD but not in those without MVD. Conclusions In patients with MVD, indobufen plus clopidogrel DAPT compared to aspirin plus clopidogrel DAPT could reduce the risk of bleeding events while preserving ischemic protection during both the first and second 6 months post-PCI. Indobufen presents an effective option for patients with MVD, especially those at high ischemic risk requiring DAPT beyond 6 months post-PCI. Trial registration The trial was registered at www.chictr.org. A Randomized Controlled Trial of Indobufen vs Aspirin after Coronary Drug-eluting Stent Implantation: the OPTION Trial (ChiCTR-IIR-17013505). (Am HeartJ 2025;282:21-29.)
BACKGROUND:The beneficial effects of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on adverse cardiac outcomes in diabetic patients are well-established. However, the effects of SGLT2i against cancer therapy-related cardiotoxicity remain understudied. We investigated the association between SGLT2i and cardiac outcomes in cancer patients. METHODS:PubMed, Embase, and the Cochrane Library were searched from their inception until September 30, 2024 for studies evaluating the effects of SGLT2i in patients with cancer. The primary outcomes included incident heart failure (HF), HF exacerbation, HF hospitalization, atrial fibrillation/atrial flutter (AF/AFL), myocardial infarction, and all-cause mortality. The secondary outcomes included acute kidney injury and sepsis. Odds ratio (OR) with 95% CI was pooled. RESULTS:Thirteen studies with 85,596 patients were included. Compared to non-SGLT2i use, SGLT2i treatment was associated with lower risks of incident HF (OR = 0.51, 95% CI: 0.32-0.79, P = 0.003), HF exacerbation (OR = 0.74, 95% CI: 0.63-0.87, P < 0.001), AF/AFL (OR = 0.67, 95% CI: 0.55-0.82, P < 0.001), myocardial infarction (OR = 0.61, 95% CI: 0.41-0.90, P = 0.01), and all-cause mortality (OR = 0.44, 95% CI: 0.28-0.69, P < 0.001), but not for HF hospitalization (OR = 0.58, 95% CI: 0.22-1.55, P = 0.28). As for safety outcomes, SGLT2i use was associated with lower risks of acute kidney injury (OR = 0.68, 95% CI: 0.57-0.81, P < 0.001) and sepsis (OR = 0.32, 95% CI: 0.23-0.44, P < 0.001). CONCLUSIONS:SGLT2i were associated with lower risks of incident HF, HF exacerbation, AF/AFL, myocardial infarction, all-cause mortality, acute kidney injury, and sepsis in cancer patients.
BACKGROUND:Patients undergoing complex high-risk percutaneous coronary interventions (CHIP) are prone to hemodynamic instability, and the optimal mechanical circulatory support (MCS) strategy for this population remains unclear. AIMS:This systematic review and network meta-analysis aimed to compare the short-term safety and efficacy of various MCS strategies in CHIP. METHODS:We systematically searched PubMed, Web of Science, Embase, and the Cochrane Library for studies comparing different MCS strategies in CHIP patients with short-term endpoints. The primary efficacy outcome was in-hospital or 30-day mortality. Safety outcomes included MCS-related complications, specifically bleeding and stroke. The MCS strategies evaluated were intra-aortic balloon pump (IABP), veno-arterial extracorporeal membrane oxygenation (VA-ECMO), IMPELLA, VA-ECMO + IABP, and VA-ECMO + IMPELLA (ECPELLA). A random-effects Bayesian network meta-analysis was performed, integrating both direct and indirect comparisons. RESULTS:Twelve studies involving a total of 75,274 patients were included. Both IABP (OR: 0.33; 95% CI: 0.13-0.91) and IMPELLA (OR: 0.44; 95% CI: 0.21-0.96) were associated with significantly lower short-term mortality compared to VA-ECMO. No significant differences were observed among other strategies. Rank probability analysis suggested that IABP had the highest probability of being the most effective strategy for reducing short-term mortality. Regarding safety outcomes, IABP was associated with a significantly lower bleeding risk compared to VA-ECMO (OR: 0.18; 95% CI: 0.04-0.82), VA-ECMO + IABP (OR: 0.18; 95% CI: 0.03-0.87), ECPELLA (OR: 0.12; 95% CI: 0.02-0.70), and IMPELLA (OR: 0.21; 95% CI: 0.05-0.75), with no significant difference in stroke risk across strategies. CONCLUSIONS:Among available MCS strategies for CHIP patients, IABP appears to be associated with improved short-term survival and a lower risk of bleeding, without an increased risk of stroke. These findings support IABP as a potentially preferable support option, warranting further validation in prospective clinical trials.
Chest pain, a common initial symptom in hypertrophic cardiomyopathy (HCM) patients, is closely linked to myocardial ischemia, despite the absence of significant coronary artery stenosis. This study explored microvascular dysfunction in HCM patients by employing angiography-derived microcirculatory resistance (AMR) as a novel tool for comprehensive assessment. This retrospective analysis included HCM patients with chest pain as the primary symptom and control patients without cardiac hypertrophy during the same period. The AMR was computed through angiography, providing a wire-free and adenosine-free index for evaluating microcirculatory function. Propensity score matching ensured balanced demographics between groups. This study also investigated the correlation between the AMR and clinical outcomes by utilizing echocardiography and follow-up data. After matching, 76 HCM patients and 152 controls were analyzed. While there was no significant difference in the incidence of epicardial coronary stenosis, the AMR of three epicardial coronary arteries was markedly greater in HCM patients. The criterion of an AMR ≥ 250 mmHg*s/m was that 65.7% of HCM patients experienced coronary microvascular dysfunction (CMD). Independent risk factors for CMD included increased left ventricular (LV) wall thickness (OR = 1.209, 95% CI 1.013-1.443, p = 0.036). Furthermore, an AMR_LAD ≥ 250 mmHg*s/m had an increased cumulative risk of the endpoint (log-rank p = 0.023) and was an independent risk factor for the endpoint (HR = 11.64, 95% CI 1.13-120.03, p = 0.039), providing valuable prognostic insights.
One marker of arterial stiffness (AS) is the brachial-ankle pulse wave velocity (baPWV). We aim to investigate the predictive value of baPWV with regard to new-onset atrial fibrillation (AF). All participants without AF from 2010 to 2020 in the Kailuan cohort were included. The primary endpoint was new-onset AF. Participants were categorized into three study groups based on baPWV, with a normal baPWV group as a reference. The predictive value of baPWV was analyzed as a continuous variable. Multivariable Cox proportional hazard regression models were used to investigate the association. A total of 49,872 subjects (mean age: 47.57 years old, 74.2% male) were included with a mean follow-up of 6.17 (3.95–8.46) years. The risk of AF increased as the baseline baPWV increased, whereby the adjusted hazard ratio (aHR) of the borderline AS group and the elevated AS group were 1.82 (95% confidence interval [CI]: 1.18–2.80) and 2.08 (95% CI: 1.31–3.30), respectively. When considered as a continuous variable, each 361 cm/s increase in baseline baPWV, increased the risk of AF by 21.7% (aHR: 1.22; 95% CI: 1.08–1.37). In the subgroup analysis of non-hypertensive patients, the risks of AF were significantly higher in the borderline AS group (aHR: 3.16, 95% CI: 1.74–5.74) and elevated AS group (aHR: 2.26, 95% CI: 1.02–5.05). For patients with elevated BMI, the risk of AF in the elevated AS group was significantly higher (aHR: 1.69, 95% CI: 1.00–2.83). Baseline baPWV was associated with new-onset AF after adjustments. (Trial registration site and registration number are, respectively, http://www.chictr.org.cn/index.aspx and ChiCTR-TNRC-11001489).
Background and aimsPostoperative atrial fibrillation (POAF) is a frequent complication following cardiac surgery and is associated with adverse clinical outcomes. Our study aimed at determining the clinical and echocardiographic predictors of POAF in patients with cardiac surgery and management of this group of patients may improve their outcome.MethodsWe prospectively enrolled patients from the department of cardiovascular surgery in the Second Hospital of Tianjin Medical University from October 23, 2020 to October 30, 2022, without a history of atrial fibrillation. Cox regression was used to identify significant predictors of POAF.ResultsA total of 217 patients (79 [36.41 %] were female, 63.96 ± 12.32 years) were included. 88 (40.55 %) patients met the criteria for POAF. Cox regression showed that preoperative left atrial diameter (LAD) (HR: 1.040, 95 % CI 1.008–1.073, p = 0.013) and postoperative QRS/LVEDD (HR: 0.398, 95 % CI 0.193–0.824, p = 0.013) and E/e' (HR: 1.029, 95 % CI 1.002–1.057,p = 0.033) were predictors of POAF.ConclusionPreoperative LAD and postoperative QRS/LVEDD and E/e' were predictors of POAF in patients undergoing cardiac surgery.Trial registration sitehttp://www.chictr.org.cnRegistration numberChiCTR2200063344.
BackgroundThe spontaneous echo contrast (SEC) in patients with atrial fibrillation (AF) indicates a prethrombic state that ultimately progresses into thrombus formation. A comprehensive understanding of specific plasma metabolomics characteristics may protect AF patients from thrombus, particularly in the early stage.ObjectivesThrough the investigation of metabolic pathways, we endeavor to uncover the metabolomic characteristics associated with SEC states, and to examine the differential metabolites by which may exert their influence on thrombotic states.MethodsPatients with AF were enrolled, and the participants were divided into three groups based on the results of the echocardiogram: non-SEC, low-SEC and high-SEC group. Samples were collected and subjected to non-targeted metabolomics analysis. The analytical process included data quality control, metabolite difference analysis, component analysis, Kegg cluster analysis, etc.ResultsOur metabolic phenotype revealed a clear differential metabolic pattern between the SEC and non-SEC. Specifically, we identified 35 and 142 significantly differential metabolites in venous and atrial plasma, respectively, suggesting that SEC may be involved in pervasive metabolic dysregulation and that the degree of metabolic dysregulation in atrial plasma is more severe than that in venous blood.ConclusionPatients with SEC have a significantly different metabolic pattern compared to those without SEC. Our work promoted the understanding of mechanism of the occurrence and development of SEC, facilitated the screening of the target metabolites for its therapeutic intervention, and provided evidence for the prevention and treatment of SEC or thrombosis in AF. Our work also provided new directions for subsequent research in related fields. In conclusion, our study not only provides a theoretical basis for understanding the occurrence and development of SEC in AF, but also provides recommendations for the daily diet of AF patients with SEC, such as a balanced intake of essential amino acids, avoiding excessive intake of benzoic acid, and intake of appropriate inositol.Clinical trial numberNot applicable.
Objective: This study examined the relationship between CHA2DS2-VASc score, fibrinogen (FIB), and neutrophil-to-lymphocyte ratio (NLR) with in-stent restenosis (ISR) in patients with severe kidney disease (SKD). Methods: Between January 2017 and January 2022, patients with SKD who underwent coronary stent implantation at the Second Hospital of Tianjin Medical University were retrospectively analyzed. According to whether ISR occurred within 2 years of postoperative follow-up, 164 patients were categorized into the ISR group (n = 62) and the non-ISR group (n = 102). According to the Modification of Diet in Renal Disease (MDRD) formula, SKD is defined as an estimated glomerular filtration rate (eGFR) less than 30 mL/(min·1.73 m2). Angiographic ISR was defined as a stented coronary artery segment with more than 50% constriction during the follow-up angiography. Relevant clinical data and laboratory parameters were obtained from the hospital's medical records. Results: In total, 164 patients were included (mean age: 67.1 [10.2] years, 65.2% men), grouped into 62 patients with ISR and 102 patients without. A significant difference was found in the age, previous strokes, congestive heart failure (CHF), NLR, platelet-to-lymphocyte ratio (PLR), fibrinogen, CHA2DS2-VASc score, and risk classification of CHA2DS2-VASc score of patients in the ISR group as compared to those in the non-ISR group. In a multivariable logistic regression analysis, the CHA2DS2-VASc score, fibrinogen, and NLR were identified as independent predictors of ISR. The analysis of the receiver operating characteristic (ROC) curve revealed that the area under the curve (AUC) value was 0.714 (95% confidence interval (CI): 0.634–0.793) for the CHA2DS2-VASc score and 0.652 (95% CI: 0.565–0.739) for FIB, 0.707 (95% CI: 0.627–0.788) for NLR, and 0.797 (95% CI: 0.725–0.868) for the combination of CHA2DS2-VASc score, FIB and NLR. Conclusions: The combination of CHA2DS2-VASc score, FIB, and NLR can more accurately predict the occurrence of ISR in SKD patients.
Background Immune checkpoint inhibitor (ICI) has become a major breakthrough in the field of tumor therapy, leading to improved survival. This study evaluated the clinical and electrocardiographic characteristics of patients with ICI-related myocarditis. Methods Patients with ICI-related myocarditis were enrolled from 4 centers in China until September 2023. Demographic data (age, sex, comorbidity), types of ICI, clinical manifestations, electrocardiogram (ECG) and treatment were analyzed retrospectively. Arrhythmia and characteristics of ECG were compared according to prognosis and grading. Results A total of 29 participants (13 females with a median age of 63.25 years) with ICI-related myocarditis were enrolled. Lung cancer was the most, with a proportion of 31.03 % (9/29). The median time from the first administration of ICI to the diagnosis of myocarditis was 50 days. Camrelizumab was the main type of ICI (9/29). Most patients had non-specific symptoms, dyspnea (n = 16) and palpitation (n = 9) were common. The overall mortality rate was 37.93 % (11/29) with a median follow-up of 9(4,11) days. Compared with the survivors, P-wave abnormality was more common in participants who were dead (24.14 %vs6.90 %, p = 0.010). A total of 19 patients with severe ICI-related myocarditis were included in this study. The proportions of sinus tachycardia (34.48 %vs0.00 %, p = 0.005), premature ventricular complex (27.59 %vs0.00 %, p = 0.027) and atrioventricular block (34.48 %vs3.45 %, p = 0.044) were higher in severe ICI-related myocarditis. Conclusions Clinical manifestations of ICI-related myocarditis usually lacked specificity. ECGs can be manifested as new-onset arrhythmias, ST-T segment changes, fragmented QRS complex, abnormal P wave, prolonged QTc interval and multi‑lead low voltage.
Cardiac amyloidosis (CA) represents an emerging challenge in cardiovascular medicine, with notable clinical overlaps and diagnostic complexities when coexisting with coronary artery disease (CAD). This integrative review navigates the intricate terrain of CA and CAD, elucidating epidemiology, clinical presentations, and diagnostic considerations. Examining both immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis, we underscore their shared demographic associations, diagnostic intricacies, and potential diagnostic confounders with CAD. Notably, we emphasize the impact of CA on epicardial coronary arteries and the consequential implications for coronary microcirculation. Further exploration reveals the connection between CA and acute myocardial infarction, emphasizing early recognition as pivotal. In terms of differential diagnosis, we underscore the significance of clinical symptoms, electrocardiography, echocardiography, cardiac magnetic resonance, and bone scintigraphy. Additionally, we scrutinize the intricate realm of treatment, encompassing medication selection, antithrombotic strategies, and revascularization modalities. Our review addresses the distinctive challenges posed by CA patients’ limited tolerance for conventional therapies. This comprehensive synthesis serves as an invaluable resource for clinicians confronting the intricate intersection of CA and CAD. By offering insights into diagnostic refinement and innovative therapeutic avenues, we aim to enhance patient outcomes and quality of life within this complex clinical landscape.
A77-year-old female presented with shortness of breath and tightness of chest was admitted.Her past medical history included hypertension and she has been taking nifedipine regularly.Two years before,she was diagnosed with pericardial effusion(Figure 1)and had pericardiocentesis drainage.On physical examination,her blood pressure was 151/100 mm-Hg and her pulse rate was 91 beats/min.Physical examination revealed both lower extremities ed-ema.
AbstractAimsHeart failure (HF) is a leading cause of mortality in patients with end‐stage renal disease (ESRD) undergoing haemodialysis. Identifying novel predictors of HF is essential for improving diagnostic precision and enhancing patient outcomes.MethodsThis study included 68 participants from the Haemodialysis Centre at the Second Hospital of Tianjin Medical University. Clinical characteristics and echocardiographic data were collected and analysed. We measured the plasma of 44 cytokines to investigate their correlation with cardiac function and their potential as HF biomarkers.ResultsIn the HF with reduced ejection fraction (HFrEF) group, the levels of several cytokines, including stem cell growth factor‐β (SCGF‐β), C–X–C motif chemokine 10 (CXCL10), interleukin‐1α (IL‐1α), interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), interleukin‐16 (IL‐16), interleukin‐1 receptor antagonist protein (IL‐1Ra), interferon‐γ (IFN‐γ), tumour necrosis factor‐α (TNF‐α), leukaemia inhibitory factor (LIF), C–C motif chemokine 3 (CCL3), interleukin‐10 (IL‐10), interleukin‐2 receptor subunit alpha (IL‐2Rα), tumour necrosis factor ligand superfamily member 10 (TNFSF10), macrophage colony‐stimulating factor (M‐CSF), granulocyte colony‐stimulating factor (G‐CSF) and stem cell factor (SCF), were significantly increased, while C–C motif chemokine 11 (CCL11)/eotaxin levels were decreased compared with those in the control group (P < 0.05). Receiver operating characteristic (ROC) curve analysis highlighted TNF‐α [area under the ROC curve (AUC) = 0.85, odds ratio (OR) = 1.080, 95% confidence interval (CI): 1.033–1.128, P = 0.001], IFN‐γ (AUC = 0.84, OR = 1.836, 95% CI: 1.289–2.615, P = 0.003) and IL‐2Rα (AUC = 0.82, OR = 1.022, 95% CI: 1.009–1.035, P = 0.001) as excellent predictors for HFrEF in haemodialysis patients with ESRD, and they outperformed soluble suppression of tumourigenicity‐2 (sST2) but slightly underperformed N‐terminal pro‐brain natriuretic peptide (NT‐proBNP). IL‐2Rα (AUC = 0.77, OR = 1.018, 95% CI: 1.007–1.030, P = 0.001) demonstrated superior diagnostic capabilities when distinguishing patients with HF with left ventricular ejection fraction (LVEF) <50% from controls. IL‐2Rα emerged as a robust biomarker for left ventricular HF, while TNF‐α (AUC = 0.89, OR = 1.140, 95% CI: 1.039–1.250, P = 0.005) showed promise in assessing HF severity in patients with ESRD. IL‐2Rα (AUC = 0.80, OR = 1.017, 95% CI: 1.007–1.027, P = 0.001) also significantly predicted right ventricular systolic dysfunction. During a median follow‐up of 14 months, 10 patients (14.7%) experienced all‐cause mortality. Multivariate Cox regression analysis confirmed that plasma IL‐2Rα was an independent predictor of all‐cause death [hazard ratio (HR): 1.010, 95% CI: 1.001–1.020, P = 0.039] after adjusting for other variables.ConclusionsThis study underscores the potential of IL‐2Rα as a valuable biomarker for HF diagnosis and management in haemodialysis patients with ESRD and contributes to our understanding of this high‐risk population.
Background Immune checkpoint inhibitors (ICI) are increasingly used in the first‐line treatment of malignant tumors. There is increasing recognition of their cardiotoxicity and, in particular, their potential to lead to myocarditis. Cardiovascular magnetic resonance (CMR) can quantify pathological changes, such as myocardial edema and fibrosis. The purpose of this systematic review and meta‐analysis was to examine the evidence for the roles of CMR in predicting prognosis in ICI‐associated myocarditis. Methods PubMed, Cochrane Library, and Web of Science databases were searched until October 2023 for published works investigating the relationship between CMR parameters and adverse events in patients with ICI‐associated myocarditis. The analysis included studies reporting the incidence of late gadolinium enhancement (LGE), T1 values, T2 values, and CMR‐derived left ventricular ejection fraction (LVEF). Odds ratios (OR) and weighted mean differences (WMD) were combined for binary and continuous data, respectively. Newcastle‐Ottawa Scale was used to assess the methodological quality of the included studies. Results Five cohort studies were included (average age 65–68 years; 25.4% female). Of these, four studies were included in the meta‐analysis of LGE‐related findings. Patients with major adverse cardiovascular events (MACE) had a higher incidence of LGE compared with patients without MACE (OR = 4.18, 95% CI: 1.72–10.19, p = 0.002). A meta‐analysis, incorporating data from two studies, showed that patients who developed MACE exhibited significantly higher T1 value (WMD = 36.16 ms, 95% CI: 21.43–50.89, p < 0.001) and lower LVEF (WMD = − 8.00%, 95% CI: −13.60 to −2.40, p = 0.005). Notably, T2 value (WMD = −0.23 ms, 95% CI: −1.86 to −1.39, p = 0.779) was not associated with MACE in patients with ICI‐related myocarditis. Conclusions LGE, T1 value, and LVEF measured by CMR imaging have potential prognostic value for long‐term adverse events in patients with ICI‐related myocarditis.
BACKGROUND: CNP (C-type natriuretic peptide), an endogenous short peptide in the natriuretic peptide family, has emerged as an important regulator to govern vascular homeostasis. However, its role in the development of atherosclerosis remains unclear. This study aimed to investigate the impact of CNP on the progression of atherosclerotic plaques and elucidate its underlying mechanisms. METHODS: Plasma CNP levels were measured in patients with acute coronary syndrome. The potential atheroprotective role of CNP was evaluated in apolipoprotein E-deficient (ApoE −/− ) mice through CNP supplementation via osmotic pumps, genetic overexpression, or LCZ696 administration. Various functional experiments involving CNP treatment were performed on primary macrophages derived from wild-type and CD36 (cluster of differentiation 36) knockout mice. Proteomics and multiple biochemical analyses were conducted to unravel the underlying mechanism. RESULTS: We observed a negative correlation between plasma CNP concentration and the burden of coronary atherosclerosis in patients. In early atherosclerotic plaques, CNP predominantly accumulated in macrophages but significantly decreased in advanced plaques. Supplementing CNP via osmotic pumps or genetic overexpression ameliorated atherosclerotic plaque formation and enhanced plaque stability in ApoE −/− mice. CNP promoted an anti-inflammatory macrophage phenotype and efferocytosis and reduced foam cell formation and necroptosis. Mechanistically, we found that CNP could accelerate HIF-1α (hypoxia-inducible factor 1-alpha) degradation in macrophages by enhancing the interaction between PHD (prolyl hydroxylase domain–containing protein) 2 and HIF-1α. Furthermore, we observed that CD36 bound to CNP and mediated its endocytosis in macrophages. Moreover, we demonstrated that the administration of LCZ696, an orally bioavailable drug recently approved for treating chronic heart failure with reduced ejection fraction, could amplify the bioactivity of CNP and ameliorate atherosclerotic plaque formation. CONCLUSIONS: Our study reveals that CNP enhanced plaque stability and alleviated macrophage inflammatory responses by promoting HIF-1α degradation, suggesting a novel atheroprotective role of CNP. Enhancing CNP bioactivity may offer a novel pharmacological strategy for treating related diseases.