Platelet factors ameliorate thoracic aortic aneurysm and dissection by inhibiting the FGF-FGFR cascade activation in aortic-endothelial cell.

Thoracic aortic aneurysm and dissection (TAAD) is closely associated with vascular endothelial dysfunction. Platelet factor 4 (PF4) is crucial for maintaining vascular endothelial cell homeostasis. However, whether PF4 can influence the progression of TAAD remains unknown. In the present study, we constructed a liposome-encapsulated PF4 nanomedicine and verified its effect on BAPN-induced TAAD in vivo. We found that liposome PF4 nanoparticles (Lipo-PF4), more effectively than PF4 alone, inhibited the formation of TAAD. In vitro, PF4 improved endothelial cell function under pathological conditions by inhibiting migratory and angiogenic abilities of human aortic endothelial cells (HAECs). Mechanically, PF4 inhibited the development of TAAD and improved HAECs function by combining with heparin sulfate and blocking fibroblast growth factor-fibroblast growth factor receptor (FGF-FGFR) signaling. Taken together, we developed a nano-drug (Lipo-PF4) that effectively ameliorates the progression of TAAD by improving endothelial function. Lipo-PF4 is expected to be a therapeutic option for TAAD in the future.

Efficacy of a cysteine protease inhibitor compared with enalapril in murine heart failure models.

Cysteine proteases calpains contribute to heart failure (HF), but it remains unknown whether their inhibition provides any benefit compared to standard pharmacological treatment for HF. Here, we characterize the pharmacological properties of NPO-2270 (NPO) as a potent inhibitor of cysteine proteases. Then, we describe that acute administration of NPO in rodent models of transient ischemia at the time of reperfusion reduces myocardial infarction, while its chronic oral administration attenuates adverse remodeling and cardiac dysfunction induced by ischemic and non-ischemic pathological stimuli more effectively than enalapril when given at the same dose. Finally, we provide evidence showing that the effects of NPO correlate with calpain inhibition and the preservation of the T-tubule morphology, due at least in part to reduced cleavage of the calpain substrate junctophilin-2. Together, our data highlight the potential of cysteine protease inhibition with NPO as a therapeutic strategy for the treatment of heart failure.

Aged gut microbiota promotes arrhythmia susceptibility via oxidative stress.

Arrhythmias and sudden cardiac death (SCD) impose a significant burden. Their prevalence rises with age and is linked to gut dysbiosis. Our study aimed to determine whether aged gut microbiota affects arrhythmogenesis. Here, we demonstrated that arrhythmia susceptibility in aged mice could be transmitted to young mice using fecal microbiota transplantation (FMT). Mechanistically, increased intestinal reactive oxygen species (ROS) in aged mice reduced ion channel protein expression and promoted arrhythmias. Gut microbiota depletion by an antibiotic cocktail reduced ROS and arrhythmia in aged mice. Interestingly, oxidative stress in heart induced by hydrogen peroxide (H2O2) increased arrhythmia. Moreover, aged gut microbiota could induce oxidative stress in young mice colon by gut microbiota metabolites transplantation. Vitexin could reduce aging and arrhythmia through OLA1-Nrf2 signaling pathway. Overall, our study demonstrated that the gut microbiota of aged mice reduced cardiac ion channel protein expression through systemic oxidative stress, thereby increased the risk of arrhythmias.

FSTL-1 loaded 3D bioprinted vascular patch regenerates the ischemic heart tissue.

Cardiac patch strategies are developed as a promising approach to regenerate the injured heart after myocardial infarction (MI). This study integrated 3D bioprinting and cardioprotective paracrine signaling to fabricate vascular patch devices containing endothelial cells (ECs) and the regenerative follistatin-like 1 (FSTL1) peptide. Engineered patch supported the 3D culture of ECs in both static and dynamic culture, forming a uniform endothelium on the printed channels. Implantation of vascular patch onto a rat model of acute MI resulted in significant reduction of scar formation, left ventricle dilation, and wall thinning, as well as enhanced ejection fraction. Furthermore, increased vascularization and proliferation of cardiomyocytes were observed in hearts treated with patches. These findings highlight the remarkable capacity of 3D bioprinted vascular patch to augment the endogenous regenerative capacity of mammalian heart, together with the exogenous cardioprotective function, to serve as a robust therapeutic device to treat acute MI.

Younger epigenetic age is associated with higher cardiorespiratory fitness in individuals with airflow limitation.

We hypothesized that increased cardiorespiratory fitness (CRF) slows down a person's aging, particularly in individuals with chronic airflow limitation (CAL). Participants aged ≥40 years (n = 78) had baseline blood DNA methylation profiled and underwent cardiopulmonary cycle exercise testing at baseline and at three years. Epigenetic clocks were calculated and tested for their association with CRF using linear regression. Differentially methylated genes associated with CRF were identified using a robust linear model. Higher CRF at baseline was associated with lower age acceleration in the epigenetic clocks DNAmAgeSkinBlood (p = 0.016), DNAmGrimAge (p = 0.012), and DNAmGrimAge2 (p = 0.011). These effects were consistent in individuals with CAL (DNAmGrimAge p = 0.009 and DNAmGrimAge2 p = 0.007). CRF at three years was associated with baseline DNAmGrimAge (p = 0.015) and DNAmGrimAge2 (p = 0.011). Differentially methylated genes associated with CRF enriched multiple aging-related pathways, including cellular senescence. Enhancing CRF may be one intervention that can slow biological aging and improve health outcomes in chronic respiratory diseases.

Development of Takotsubo cardiomyopathy following spontaneous coronary artery dissection in a patient with fibromuscular dysplasia.

New-onset Takotsubo cardiomyopathy following spontaneous coronary artery dissection (SCAD) is rare. We report a middle-aged woman without significant cardiovascular risk factors, who initially presented with non-ST-elevation myocardial infarction (NSTEMI) with angiography showing sudden 'pruning' of the coronary artery consistent with SCAD. One week later, the patient returned with recurrent NSTEMI. Repeat coronary angiogram showed no change in SCAD, but ventriculogram revealed new-onset apical ballooning beyond the SCAD-affected territory, consistent with Takotsubo cardiomyopathy. Further head-to-pelvis angiogram revealed an irregular beaded appearance of the left vertebral artery consistent with fibromuscular dysplasia. The patient was managed conservatively with aspirin, carvedilol and escitalopram with complete resolution of cardiac and mood symptoms. Our case supports an association between SCAD and Takotsubo cardiomyopathy in a potentially mutually aggravating process. Clinical vigilance is therefore required to rule out the other condition when one of the two entities is diagnosed.

Bone cement implantation syndrome: the role of echocardiography and multidisciplinarity.

Bone cement implantation syndrome (BCIS) is a potentially serious complication after joint replacement surgery, resulting from bone marrow debris and cement embolisation, culminating in pulmonary and cardiovascular collapse. Echocardiography aids in diagnosis and management. We present a woman in her 80s with grade II BCIS. CT angiogram was inconclusive, but echocardiography revealed hyperechogenic material and right ventricular dysfunction, confirming the diagnosis. She received cardiovascular and respiratory support in a level II intensive care unit, showing full recovery of the right ventricle function when it was later reassessed. This potentially fatal condition is successfully managed if recognised early with adequate supportive care. Echocardiography might guide the diagnosis, consolidating supportive measures.

Improving cardiovascular risk stratification through multivariate time-series analysis of cardiopulmonary exercise test data.

Nowadays cardiorespiratory fitness (CRF) is assessed using summary indexes of cardiopulmonary exercise tests (CPETs). Yet, raw time-series CPET recordings may hold additional information with clinical relevance. Therefore, we investigated whether analysis of raw CPET data using dynamic time warping combined with k-medoids could identify distinct CRF phenogroups and improve cardiovascular (CV) risk stratification. CPET recordings from 1,399 participants (mean age, 56.4 years; 37.7% women) were separated into 5 groups with distinct patterns. Cluster 5 was associated with the worst CV profile with higher use of antihypertensive medication and a history of CV disease, while cluster 1 represented the most favorable CV profile. Clusters 4 (hazard ratio: 1.30; p = 0.033) and 5 (hazard ratio: 1.36; p = 0.0088) had a significantly higher risk of incident adverse events compared to clusters 1 and 2. The model evaluation in the external validation cohort revealed similar patterns. Therefore, an integrative CRF profiling might facilitate CV risk stratification and management.

Prognostic nomogram for the patency of wrist autologous arteriovenous fistula in first year.

Autologous arteriovenous fistula (AVF) is preferred in hemodialysis patients. Maintaining its patency is a critical problem. This study aimed to create a nomogram model for predicting 1-year primary patency of AVF. Consequently, a total of 414 patients were retrospectively enrolled and randomly allocated to training and validation cohorts. Risk factors were identified by multivariable logistic regression and used to create a nomogram model. Performance of the model was evaluated by receiver operating characteristic (ROC) curve, Hosmer-Lemeshow test, and calibration curve. The results suggested that diameter of cephalic vein, low-density lipoprotein, glycosylated hemoglobin (%), and C-reactive protein were risk factors which could predict the patency of AVF. Area under ROC curves for training and validation cohorts were 0.771 and 0.794, respectively. Calibration ability was satisfactory in both cohorts. Therefore, present nomogram model could predict the 1-year primary patency of AVF.

A novel vital sign pattern predicts sepsis-related myocardial injury mortality.

Non-invasive, real-time monitorable indicators for early assessment of sepsis-associated myocardial injury (SMI) are still lacking. We aimed to develop non-invasive, real-time indicators for early assessment of SMI using bedside heart rate (HR) and diastolic arterial pressure (DAP) monitors. In this multi-center cohort study, piece-wise exponential additive mixed models were used to estimate the exposure window and time fraction of the hazardous exposure proportion, and secondarily to analyze the exposure characterization on this basis to identify high-risk exposure pattern. In total, 20,043 patients were finally included; we found that SMI patients had the highest survival rate when HR was <90 bpm or DAP was between 50 and 70 mmHg. Further investigation revealed that the SMI high-risk exposure pattern was the H1D-1 (HR ≥ 90 bpm and DAP ≤ 50 mmHg, exposure proportion > 0.3 and 0.2, respectively, and exposure window on admission day 1). H1D-1 exposure pattern using glucocorticoids significantly increased the risk of mortality in H1D-1. Validation against various methodologies and data sources demonstrated acceptable consistency.

[Legal aspects in digital cardiology]. / Rechtliche Aspekte in der digitalen Kardiologie.

Digital assistants have become an indispensable tool in modern cardiology. The associated technological progress offers a significant potential to increase the efficiency of medical processes, enable more precise diagnoses in a shorter time, and thus improve patient care. However, the integration of digital assistants into clinical cardiology also raises new challenges and questions, particularly regarding the handling of legal issues. This review article aims to raise awareness of individual legal issues resulting from the use of digital technologies in cardiology. The focus is on how to deal with various legal challenges that cardiologists face, including issues related to treatment freedom, professional confidentiality and data protection. The integration of digital assistants in cardiology leads to a noticeable improvement in efficiency and quality of patient care, but at the same time, it involves a variety of legal challenges that need to be carefully addressed.

Cardiac arrest with severe airway stenosis due to retropharyngeal haematoma secondary to Stanford type B acute aortic dissection.

This was the case of a male patient in his 60s, who suddenly collapsed. When the ambulance team arrived, the initial waveform was pulseless electrical activity; accordingly, a supraglottic airway device was inserted, and the patient was immediately transported to a referring hospital. On arrival, the patient resumed spontaneous circulation, the patient was diagnosed with Stanford type B acute aortic dissection and was referred to the author's hospital, where diffuse swelling of the anterior cervical region was revealed. CT performed by the previous hospital revealed compression of the trachea. The cause of cardiac arrest was considered to be severe airway stenosis secondary to a retropharyngeal haematoma associated with Stanford type B acute aortic dissection. Stanford type B acute aortic dissection can be complicated by retropharyngeal haematomas, which can lead to airway obstruction and even cardiac arrest. This condition also requires careful airway examination.

Silent stealth: painless aortic dissection masquerading as heart failure.

A male patient in his 50s presented to the emergency department with a three-day history of shortness of breath, New York Heart Association class IV, and oxygen desaturation. His physical examination revealed a large volume radial pulse with bibasal crepitation in the lungs and a soft diastolic murmur in the aortic area on auscultation of his heart. He was managed on the line of decompensated heart failure. Transthoracic echocardiography showed a dissection flap in the ascending aorta with acute severe aortic regurgitation. A subsequent urgent CT angiography of the whole aorta confirmed a complex type A aortic dissection with an aneurysmal ascending aorta. An emergency type A aortic dissection repair (modified Bentall's procedure) was done. The patient made a good recovery, was discharged successfully 2 weeks after the procedure and was doing well on postoperative follow-up.

Protective role of acetylcholine and the cholinergic system in the injured heart.

This review explores the roles of the cholinergic system in the heart, comprising the neuronal and non-neuronal cholinergic systems. Both systems are essential for maintaining cardiac homeostasis by regulating the release of acetylcholine (ACh). A reduction in ACh release is associated with the early onset of cardiovascular diseases (CVDs), and increasing evidence supports the protective roles of ACh against CVD. We address the challenges and limitations of current strategies to elevate ACh levels, including vagus nerve stimulation and pharmacological interventions such as cholinesterase inhibitors. Additionally, we introduce alternative strategies to increase ACh in the heart, such as stem cell therapy, gene therapy, microRNAs, and nanoparticle drug delivery methods. These findings offer new insights into advanced treatments for regenerating the injured human heart.

Leukocyte mitochondrial DNA copy number and cardiovascular disease: A systematic review and meta-analysis of cohort studies.

Increasing cohort studies have examined the link between mitochondrial DNA copy number (mtDNA-CN) and cardiovascular disease (CVD), with inconsistent findings. We searched PubMed, EMBASE, and Web of Science up to July 11, 2023 and used a random-effects model to calculate summary hazard ratios (HRs) and 95% confidence intervals (CIs). This systematic review and meta-analysis included 8 articles encompassing 29 studies with 646,398 participants. Individuals with the lowest mtDNA-CN had a summary HR of 1.27 (95% CI 1.02-1.59) for CVD, 1.18 (95% CI 0.92-1.50) for coronary heart disease (CHD), 1.10 (95% CI 0.89-1.37) for stroke, and 1.30 (95% CI 1.07-1.56) for heart failure (HF). Decreased mtDNA-CN is linked to an increased risk of CVD and HF but not CHD and stroke. These findings suggest mtDNA-CN from leukocytes may be a potential early biomarker for CVD. However, more prospective studies with long follow-up are needed.

Post-translational modifications of pyruvate dehydrogenase complex in cardiovascular disease.

Pyruvate dehydrogenase complex (PDC) is a crucial enzyme that connects glycolysis and the tricarboxylic acid (TCA) cycle pathway. It plays an essential role in regulating glucose metabolism for energy production by catalyzing the oxidative decarboxylation of pyruvate to acetyl coenzyme A. Importantly, the activity of PDC is regulated through post-translational modifications (PTMs), phosphorylation, acetylation, and O-GlcNAcylation. These PTMs have significant effects on PDC activity under both physiological and pathophysiological conditions, making them potential targets for metabolism-related diseases. This review specifically focuses on the PTMs of PDC in cardiovascular diseases (CVDs) such as myocardial ischemia/reperfusion injury, diabetic cardiomyopathy, obesity-related cardiomyopathy, heart failure (HF), and vascular diseases. The findings from this review offer theoretical references for the diagnosis, treatment, and prognosis of CVD.

The weight reduction mediated by anti-obesity medication and the cardiovascular outcome.

The association between anti-obesity medications (AOMs) as well as their weight-loss effects and cardiovascular outcomes need to be comprehensively investigated. We searched PubMed, Embase, the Cochrane Center Register of Controlled Trials for Studies, and Clinicaltrial.gov website from the inception to April 2024 and included 129 randomized controlled trials (RCTs) of AOMs. When compared with placebo, every 5 kg weight reduction mediated by AOMs was associated with the reduced risks of 3-point major adverse cardiovascular events (relative risk [RR] 0.72, 95% confidence interval [CI] 0.60-0.85), myocardial infarction (RR 0.75, 95% CI 0.60-0.95), stroke (RR 0.60, 95% CI 0.42-0.85), and heart failure (RR 0.71, 95% CI 0.54-0.95). As for glucagon-like peptide 1 receptor agonist (GLP-1RA)-users, similar cardiovascular benefits were also observed with 5 kg weight loss. This study indicated that the weight reductions mediated by AOMs were associated with cardiovascular benefits observed in AOM-users.

Severe postural hypotension and sinus bradycardia with thalidomide in patients with erythema nodosum leprosum.

Two men in their 60s and 40s were diagnosed with erythema nodosum leprosum based on the development of recurrent painful ulcers and nodules, respectively, for the previous 6 months. Thalidomide 100 mg four times a day, along with MB-MDT, was started in both patients. Both patients experienced severe dizziness on rising from a seated posture soon after initiation of thalidomide and a decrease in blood pressure and heart rate. Cardiovascular/neurology examination and routine blood investigations were normal. An autonomic nervous system assessment indicated bradycardia, postural hypotension and decreased cardiac autonomic function. The dosage of thalidomide was then gradually reduced over 4-5 days to 100 mg/day following a suspicion that thalidomide was the cause of postural hypotension. The dizziness subsided, and blood pressure and heart rate returned to normal.We concluded that thalidomide was the culprit behind bradycardia and dose- dependent postural hypotension.