Overexpression of VEGFα as a biomarker of endothelial dysfunction in aortic tissue of α-GAL-Tg/KO mice and its upregulation in the serum of patients with Fabry’s disease

Scientific Data

Publisher Correction: High resolution optical mapping of cardiac electrophysiology in pre-clinical models - PMC Back to Top Skip to main content NIH NLM Logo Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation Search PMC Full-Text Archive Search in PMC Advanced Search User Guide Journal List Sci Data v.11; 2024 PMC10796748 Other Formats PDF (618K) Actions Cite Collections Share Permalink Copy RESOURCES Similar articles Cited by other articles Links to NCBI Databases Journal List Sci Data v.11; 2024 PMC10796748 As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Logo of sdata Sci Data. 2024; 11: 93. Published online 2024 Jan 18. doi: 10.1038/s41597-024-02941-w …

Journal of Cardiovascular Magnetic Resonance

Background: The left atrial volume (LAV) is a crucial cardiac parameter in several clinical settings such as in atrial fibrillation or heart failure for the assessment of diastolic dysfunction and cardiac risk. Currently available LAV reference values were defined by 2d transthoracic echocardiography (2d-TTE). However, LAV measurements are routine part of CMR protocols, though data on the interchangeability of LAV values between CMR and 2d-TTE remain scarce.Methods: We performed CMR (3 T scanner MAGNETOM™ Skyra, Siemens Healthineers, Erlangen, Germany) and 2d-TTE in 2126 participants of the Hamburg City Health Study (HCHS), a population-based cohort study of the middle-aged population in Hamburg. LAV was assessed in TTE from the 4-and 2-chamber view by the method of disk summation. In CMR, LAV was also measured in cine images from the 2-and 4-chamber orientation, employing the …

Biomedicines

Desmoglein-2 mutations are detected in 5–10% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Endurance training accelerates the development of the ARVC phenotype, leading to earlier arrhythmic events. Homozygous Dsg2 mutant mice develop a severe ARVC-like phenotype. The phenotype of heterozygous mutant (Dsg2mt/wt) or haploinsufficient (Dsg20/wt) mice is still not well understood. To assess the effects of age and endurance swim training, we studied cardiac morphology and function in sedentary one-year-old Dsg2mt/wt and Dsg20/wt mice and in young Dsg2mt/wt mice exposed to endurance swim training. Cardiac structure was only occasionally affected in aged Dsg20/wt and Dsg2mt/wt mice manifesting as small fibrotic foci and displacement of Connexin 43. Endurance swim training increased the right ventricular (RV) diameter and decreased RV function in Dsg2mt/wt mice but not in wild types. Dsg2mt/wt hearts showed increased ventricular activation times and pacing-induced ventricular arrhythmia without obvious fibrosis or inflammation. Preload-reducing therapy during training prevented RV enlargement and alleviated the electrophysiological phenotype. Taken together, endurance swim training induced features of ARVC in young adult Dsg2mt/wt mice. Prolonged ventricular activation times in the hearts of trained Dsg2mt/wt mice are therefore a potential mechanism for increased arrhythmia risk. Preload-reducing therapy prevented training-induced ARVC phenotype pointing to beneficial treatment options in human patients.

Europace

Aims Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Methods and results Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to …

Biomedicines

Desmoglein-2 mutations are detected in 5–10% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Endurance training accelerates the development of the ARVC phenotype, leading to earlier arrhythmic events. Homozygous Dsg2 mutant mice develop a severe ARVC-like phenotype. The phenotype of heterozygous mutant (Dsg2mt/wt) or haploinsufficient (Dsg20/wt) mice is still not well understood. To assess the effects of age and endurance swim training, we studied cardiac morphology and function in sedentary one-year-old Dsg2mt/wt and Dsg20/wt mice and in young Dsg2mt/wt mice exposed to endurance swim training. Cardiac structure was only occasionally affected in aged Dsg20/wt and Dsg2mt/wt mice manifesting as small fibrotic foci and displacement of Connexin 43. Endurance swim training increased the right ventricular (RV) diameter and decreased RV function in Dsg2mt/wt mice but not in wild types. Dsg2mt/wt hearts showed increased ventricular activation times and pacing-induced ventricular arrhythmia without obvious fibrosis or inflammation. Preload-reducing therapy during training prevented RV enlargement and alleviated the electrophysiological phenotype. Taken together, endurance swim training induced features of ARVC in young adult Dsg2mt/wt mice. Prolonged ventricular activation times in the hearts of trained Dsg2mt/wt mice are therefore a potential mechanism for increased arrhythmia risk. Preload-reducing therapy prevented training-induced ARVC phenotype pointing to beneficial treatment options in human patients.

Frontiers in Cardiovascular Medicine

Introduction Fabry's disease is an X-linked lysosomal storage disorder caused by reduced activity of α-galactosidase A (GAL), leading to premature death on account of renal, cardiac, and vascular organ failure. Accumulation of the GAL substrate globotriaosylceramide (Gb3) in endothelial and smooth muscle cells is associated with early vascular cell damage, suggesting endothelial dysfunction as a driver of cardiorenal organ failure. Here, we studied the vascular expression of the key angiogenic factors, VEGFα and its antagonist angiostatin, in Fabry α-GAL-Tg/KO mice and determined circulating VEGFα and angiostatin serum levels in patients with Fabry’s disease and healthy controls. Methods Cryopreserved aortic vessels from six α-GAL-Tg/KO and six wild-type (WT) mice were obtained and VEGFα and angiostatin levels were determined by performing Western blot analysis. VEGFα expression was visualized by an immunohistochemical staining of paraffin aortic rings. In addition, VEGFα and angiostatin serum levels were measured by using an enzyme-linked immunosorbent assay in 48 patients with genetically verified Fabry's disease (50% male) and 22 healthy controls and correlated with disease severity markers such as lyso-Gb3, albuminuria, NTproBNP, high-sensitive troponin T (hsTNT), and myocardial wall thickness. Results It was found that there was a significant increase in VEGFα protein expression (1.66 ± 0.35 vs. 0.62 ± 0.16, p = 0.0009) and a decrease in angiostatin expression (0.024 ± 0.007 vs. 0.053 ± 0.02, p = 0.038) in aortic lysates from α-GAL-Tg/KO compared with that from WT mice. Immunohistochemical …

European Heart Journal: Acute Cardiovascular Care

Aims Veno-arterial extracorporeal membrane oxygenation therapy (VA-ECMO) restores circulation and tissue oxygenation in cardiogenic shock (CS) patients, but can also lead to complications. This study aimed to quantify VA-ECMO complications and analyse their association with overall survival as well as favourable neurological outcome (cerebral performance categories 1 + 2). Methods and results All-comer patients with CS treated with VA-ECMO were retrospectively enrolled from 16 centres in four countries (2005–2019). Neurological, bleeding, and ischaemic adverse events (AEs) were considered. From these, typical VA-ECMO complications were identified and analysed separately as device-related complications. n = 501. Overall, 118 were women (24%), median age was 56.0 years, median lactate was 8.1 mmol/L. Acute myocardial infarction caused CS in 289 …

Frontiers in Cardiovascular Medicine

Introduction Fabry's disease is an X-linked lysosomal storage disorder caused by reduced activity of α-galactosidase A (GAL), leading to premature death on account of renal, cardiac, and vascular organ failure. Accumulation of the GAL substrate globotriaosylceramide (Gb3) in endothelial and smooth muscle cells is associated with early vascular cell damage, suggesting endothelial dysfunction as a driver of cardiorenal organ failure. Here, we studied the vascular expression of the key angiogenic factors, VEGFα and its antagonist angiostatin, in Fabry α-GAL-Tg/KO mice and determined circulating VEGFα and angiostatin serum levels in patients with Fabry’s disease and healthy controls. Methods Cryopreserved aortic vessels from six α-GAL-Tg/KO and six wild-type (WT) mice were obtained and VEGFα and angiostatin levels were determined by performing Western blot analysis. VEGFα expression was visualized by an immunohistochemical staining of paraffin aortic rings. In addition, VEGFα and angiostatin serum levels were measured by using an enzyme-linked immunosorbent assay in 48 patients with genetically verified Fabry's disease (50% male) and 22 healthy controls and correlated with disease severity markers such as lyso-Gb3, albuminuria, NTproBNP, high-sensitive troponin T (hsTNT), and myocardial wall thickness. Results It was found that there was a significant increase in VEGFα protein expression (1.66 ± 0.35 vs. 0.62 ± 0.16, p = 0.0009) and a decrease in angiostatin expression (0.024 ± 0.007 vs. 0.053 ± 0.02, p = 0.038) in aortic lysates from α-GAL-Tg/KO compared with that from WT mice. Immunohistochemical …

Heart Rhythm

BackgroundPulsed-field ablation (PFA) is a nonthermal energy source for ablation of cardiac arrhythmias. This study investigated the prospective outcomes of a novel PFA generator in conjunction with a commercially available, contact force-sensing, focal ablation catheter.ObjectiveThe purpose of this study was to assess the feasibility, safety, and lesion characteristics of point-by-point PFA in consecutive patients undergoing repeat ablation of atrial fibrillation (AF).MethodsThe study involved reisolation of pulmonary veins (PVs) with electrical reconnection and the creation of an anterior line (AL) in patients with anterior substrate or durable pulmonary vein isolation (PVI).ResultsIn 24 patients (46% female; mean age 67 ± 10 years; 67% persistent AF), successful reisolation of 27 of 27 reconnected PVs (100%) was performed. In 19 patients, AL ablation was performed, with bidirectional block in 16 (84%), median …

Nature Cardiovascular Research

Viral myocarditis is characterized by infiltration of mononuclear cells essential for virus elimination. GPR15 has been identified as a homing receptor for regulatory T cells in inflammatory intestine diseases, but its role in inflammatory heart diseases is still elusive. Here we show that GPR15 deficiency impairs coxsackievirus B3 elimination, leading to adverse cardiac remodeling and dysfunction. Delayed recruitment of regulatory T cells in GPR15-deficient mice was accompanied by prolonged persistence of cytotoxic and regulatory T cells. In addition, RNA sequencing revealed prolonged inflammatory response and altered chemotaxis in knockout mice. In line, we identified GPR15 and its ligand GPR15L as an important chemokine receptor–ligand pair for the recruitment of regulatory and cytotoxic T cells. In summary, the insufficient virus elimination might be caused by a delayed recruitment of T cells as well as …

Cardiovascular Research

Background Atrial fibrillation (AF) and concomitant cardiometabolic disease processes interact and combine to lead to adverse events such as stroke, heart failure, myocardial infarction, and cardiovascular death. Circulating biomolecules provide quantifiable proxies for cardiometabolic disease processes. Their role in defining subphenotypes of AF is not known. Methods and results This prespecified analysis of the EAST-AFNET4 biomolecule study assigned patients to clusters using polytomous variable latent class analysis (poLCA) based on baseline concentrations of thirteen precisely-quantified biomolecules potentially reflecting ageing, cardiac fibrosis, metabolic dysfunction, oxidative stress, cardiac load, endothelial dysfunction, and inflammation. In each cluster, rates of cardiovascular death, stroke, or hospitalization for heart failure or acute coronary syndrome, the primary …

Circulation

BACKGROUND SGLT2 (sodium-glucose cotransporter 2) inhibitors (SGLT2i) can protect the kidneys and heart, but the underlying mechanism remains poorly understood. METHODS To gain insights on primary effects of SGLT2i that are not confounded by pathophysiologic processes or are secondary to improvement by SGLT2i, we performed an in-depth proteomics, phosphoproteomics, and metabolomics analysis by integrating signatures from multiple metabolic organs and body fluids after 1 week of SGLT2i treatment of nondiabetic as well as diabetic mice with early and uncomplicated hyperglycemia. RESULTS Kidneys of nondiabetic mice reacted most strongly to SGLT2i in terms of proteomic reconfiguration, including evidence for less early proximal tubule glucotoxicity and a broad downregulation of the apical uptake transport machinery (including sodium, glucose, urate, purine bases, and amino acids …

Atrial fibrillation is one of the most common cardiac arrhythmias and is a major cause of ischaemic stroke. Recent findings indicate the importance of atrial fibrillation burden (device-detected, subclinical, or paroxysmal and persistent or permanent) and whether atrial fibrillation was known before stroke onset or diagnosed after stroke for the risk of recurrence. Secondary prevention in patients with atrial fibrillation and stroke aims to reduce the risk of recurrent ischaemic stroke. Findings from randomised controlled trials assessing the optimal timing to introduce direct oral anticoagulant therapy after a stroke show that early start (ie, within 48 h for minor to moderate strokes and within 4–5 days for large strokes) seems safe and could reduce the risk of early recurrence. Other promising developments regarding early rhythm control, left atrial appendage occlusion, and novel factor XI inhibitor oral anticoagulants suggest …

European Heart Journal

Background Direct, non-vitamin K antagonist oral anticoagulants (DOACs/NOACs) have become the first-choice therapy for stroke prevention in patients with atrial fibrillation (AF) at risk of stroke. Data on long-term effectiveness and safety of NOACs are scarce and not available from randomised clinical trials. Purpose We analysed 4-year outcome data in 13,632 European patients with AF treated with the NOAC, edoxaban. Methods This is the first report of the four-year follow-up information collected in the ETNA-AF-Europe (NCT02944019) study. It is a prospective registry, conducted in 825 centres enrolling edoxaban-treated patients in 10 European countries. Design and follow-up were agreed with the European Medicines Agency as part of the post-approval safety assessment of edoxaban. Key efficacy and safety outcomes were adjudicated …

European Heart Journal-Cardiovascular Pharmacotherapy

The incidence and prevalence of atrial fibrillation (AF) are increasing in parallel with global ageing and increase in patients with cardiovascular risk factors such as hypertension, obesity, and diabetes. Although the physiological mechanisms responsible for the development of AF are multifactorial, inflammation (including continuous low-grade inflammation associated with ageing), vascular pathology, and cardiac structural and electrical remodelling are key contributors. 1 New strategies for the primary prevention of AF such as targeting inflammatory and vascular pathways are required to slow down the rapid increase in global prevalence and the burden of associated disability-adjusted life years. 1 Aspirin could be considered for primary AF prevention given its anti-inflammatory and vascular protection properties in addition to its antithrombotic activity. 2 However, investigators have not tested whether low-dose …

European Heart Journal

Background and Aims Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. Methods This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation …

Circulation Reports

Background: This study reports prescribing patterns and the 1-year effectiveness and safety of edoxaban in an Asian cohort of Edoxaban Treatment in routiNe clinical prActice (ETNA)-Atrial Fibrillation (AF) patients.Methods and Results: The Global ETNA-AF program integrates prospective, observational, noninterventional regional studies, collecting data on characteristics and clinical outcomes of patients with AF receiving edoxaban for stroke prevention. Baseline characteristics, medical history, and 1-year clinical event rates were assessed in patients from South Korea, Taiwan, Hong Kong, and Thailand. Clinically relevant events assessed at 12 months included all-cause death, cardiovascular death, ischemic and hemorrhagic stroke, systemic embolic events (SEEs), bleeding, and net clinical outcome (NCO). Overall, 3,359 patients treated with edoxaban 60 or 30 mg once daily completed 1-year follow-up; 70.9% of patients received recommended dosing according to local labels. Baseline mean±standard deviation age was 71.7±9.6 years, CHA 2 DS 2-VASc score was 3.1±1.5, and modified HAS-BLED score was 2.3±1.1. Mean age and sex were similar across countries/regions. The 1-year event rate for all-cause death was 1.8%; major bleeding, 1.3%; ischemic stroke, 1.1%; cardiovascular mortality, 0.7%; hemorrhagic stroke, 0.3%; SEEs, 0%; and NCO, 4.1%; with differences observed between countries/regions and dosing groups.Conclusions: Most Asian patients with AF were prescribed recommended edoxaban dosing in routine care settings. At 1-year follow-up, this analysis supports the effectiveness and safety of edoxaban in these patients.

Clinical Research in Cardiology

BackgroundInfective endocarditis (IE) is characterized by high morbidity and mortality rates, despite recent improvements in diagnostics and treatment. We aimed to investigate incidence, clinical characteristics, and in-hospital mortality in a large-scale nationwide cohort.MethodsUsing data from the German Federal Bureau of Statistics, all IE cases in Germany between 2007 and 2019 were analyzed. Logistic regression models were fitted to assess associations between clinical factors and in-hospital mortality.ResultsIn total, 86,469 patients were hospitalized with IE between 2007 and 2019. The mean age was 66.5 ± 14.7 years and 31.8% (n = 27,534/86,469) were female. Cardiovascular (CV) comorbidities were common. The incidence of IE in the German population increased from 6.3/100,000 to 10.2/100,000 between 2007 and 2019. Staphylococcus (n = 17,673/86,469; 20.4%) and streptococcus (n = 17 …

Frontiers in Cardiovascular Medicine

Cardiovascular diseases (CVD) substantially burden our societal health and healthcare system. With 2.2 million deaths in females and 1.9 million deaths in males, CVD remain the leading cause of death and disability within Europe (1). Furthermore, in 2019 there were 12.7 million new cases and 113 million people were living with CVD in Europe (1). Cardiac rehabilitation (CR) mitigates this growing epidemic and is a class 1A recommendation in all guidelines (2), based on evidence indicating decreased morbidity and mortality, an increased quality of life (QoL), better physical functioning and good cost-effectiveness (3–5). To date, depending on the intervention (eg, percutaneous interventions vs. cardiac surgery), patients with CVD are recommended to participate in a CR program starting within the first 6 weeks after treatment (2). Those CR programs have traditionally been delivered as ambulatory supervised centre-based programs, with patients visiting the hospital 2–3 times per week (2). However, uptake rates are low across Europe, with less than 40% of eligible patients participating after an acute event (2). The main barriers patients report for non-participation in a supervised centre-based program are intrapersonal (eg, physical condition, presence of multiple co-morbidities, other responsibilities), interpersonal (eg, social obligations, lack of social support), environmental (eg, weather, distance, facilities) or organizational (eg, lack of time, financial limitations)(6). If we are to achieve uptake rates of CR well above 50% such as recommended by the European Association of Preventive Cardiology quality indicators (2) or the United Kingdom’s …

Frontiers in Cardiovascular Medicine

BackgroundArtificial intelligence (AI) has shown promise in the early detection of various cardiac conditions from a standard 12-lead electrocardiogram (ECG). However, the ability of AI to identify abnormalities from single-lead recordings across a range of pathological conditions remains to be systematically investigated. This study aims to assess the performance of a convolutional neural network (CNN) using a single-lead (D1) rather than a standard 12-lead setup for accurate identification of ECG abnormalities.MethodsWe designed and trained a lightweight CNN to identify 20 different cardiac abnormalities on ECGs, using data from the PTB-XL dataset. With a relatively simple architecture, the network was designed to accommodate different combinations of leads as input (< 100,000 learnable parameters). We compared various lead setups such as the standard 12-lead, D1 alone, and D1 paired with an …

Frontiers in Cardiovascular Medicine

Background Hypertension is highly prevalent and particularly difficult to treat adequately in patients with chronic kidney disease (CKD). The relative contribution of volume overload and vascular mechanisms to blood pressure measures in CKD and whether these effects differ in non-dialysis compared to dialysis patients is unknown. Methods We determined the potential impact of volume load (stroke volume) and vascular mechanisms (inverse of total arterial compliance (inv TAC) and systemic vascular resistance (SVR)) on mean and brachial and aortic systolic blood pressures in 67 non-dialysis and 48 dialysis chronic kidney disease (CKD) patients. Relationships were determined in confounder adjusted regression models. Results Stroke volume (p value=0.003) was more strongly associated with mean arterial pressure than SVR (p value= 0.9) (p value for difference=0.03). When stroke volume and SVR were …

Frontiers in Cardiovascular Medicine

Background Randomized evidence suggested improved outcomes in fractional flow reserve (FFR) guidance of coronary revascularization compared to medical therapy in well-defined patient cohorts. However, the impact of FFR-guided revascularization on long-term outcomes of unselected patients with chronic or acute coronary syndromes (ACS) is unknown. Aims The FLORIDA (Fractional FLOw Reserve In cardiovascular DiseAses) study sought to investigate outcomes of FFR-guided vs. angiography-guided treatment strategies in a large, real-world cohort. Methods This study included patients enrolled into the German InGef Research Database. Patients undergoing coronary angiography between January 2014 and December 2015 were included in the analysis. Eligible patients had at least one inpatient coronary angiogram for suspected coronary artery disease between January 2014 and December 2015. Patients were stratified into FFR arm if a coronary angiography with adjunctive FFR measurement was performed, otherwise into the angiography-only arm. Matching was applied to ensure a balanced distribution of baseline characteristics in the study cohort. Patients were followed for 3 years after index date and primary endpoint was all-cause mortality. Results In the matched population, mortality at 3 years was 9.6% in the FFR-assessed group and 12.6% in the angiography-only group (p = 0.002), corresponding to a 24% relative risk reduction with use of FFR. This effect was most pronounced in patients in whom revascularization was deferred based on FFR (8.7% vs. 12.3%, p = 0.04) and in high-risk subgroups including patients …

Frontiers in Cardiovascular Medicine

Myocardial infarction (MI) remains a significant global health concern prompting ongoing advancements in diagnostic and therapeutic approaches. Accurate assessment of myocardial viability is crucial in guiding therapeutic decisions and predicting patient outcomes. While the body of literature on cardiac MRI (CMR) provides insights into viability assessment, existing studies lack comprehensive analyses to inform practitioners about the nuances of measurements and their implications for patient selection and outcomes in chronic infarction. This article aims to propose an assessment method and discuss the need for new research.

Frontiers in Cardiovascular Medicine

Introduction The use of contemporary drug-eluting stents (DES) has significantly improved outcomes of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). However, concerns exist regarding the long-term proinflammatory effects of durable polymer coatings used in most DES, potentially leading to long-term adverse events. First-generation polymer-free stent technologies, such as sirolimus- and probucol-eluting stents (PF-SES), have shown an excellent safety and efficacy profile. The aim of this study was to evaluate the safety and efficacy of the new ultrathin Coroflex ISAR NEO PF-SES, in a more-comers PCI population. Methods The CAESAR (a more-Comers populAtion trEated with an ultrathin struts polimer-free Sirolimus stent: An Italian post-maRketing study) registry is a multicenter, prospective study conducted in Italy, enrolling more-comers CAD patients undergoing PCI with the Coroflex ISAR NEO stent. Patients with left main (LM) disease, cardiogenic shock (CS), or severely reduced left-ventricular ejection fraction (LVEF) were excluded. The primary endpoint was target-lesion revascularization (TLR) at 1 year. Results A total of 425 patients were enrolled at 13 centers (mean age 66.9 ± 11.6 years, Diabetes mellitus 29%, acute coronary syndrome 67%, chronic total occlusion 9%). Of these, 40.9% had multivessel disease (MVD) and in 3.3% cases, the target lesion was in-stent restenosis (ISR). Clinical device success was reached in 422 (99.6%) cases. At 1 year, only two (0.5%) subjects presented ischemia-driven TLR. The 1-year rates of target vessel revascularization and MACE were 0 …

Frontiers in Cardiovascular Medicine

Introduction Coronary artery bypass grafting (CABG) is the most common cardiac surgical procedure. The prognosis of revascularization via CABG is determined by the patency of the used grafts, for which an intact endothelium is essential. The degree of ischemia-reperfusion injury (IRI), which occurs during the harvest and implantation of the grafts, is an important determinant of graft patency. Preconditioning with aspirin, a nonsteroidal anti-inflammatory drug has been shown to reduce the functional and molecular damage of arterial grafts in a rodent model. Studies have found that the zinc-aspirin complex may be able to exert an even better protective effect in pathological cardiovascular conditions. Thus, our aim was to characterize the protective effect of zinc-aspirin complex on free arterial grafts in a rodent model of revascularization. Methods Donor Lewis rats were treated with either zinc-aspirin, aspirin, or placebo (n = 8) for 5 days, then the aortic arches were harvested and stored in cold preservation solution and implanted heterotopically in the abdominal cavity of the recipient rats, followed by 2 h of reperfusion. There was also a non-ischemia-reperfusion control group (n = 8). Functional measurements using organ bath and histomorphological changes using immunohistochemistry were analyzed. Results The endothelium dependent maximal vasorelaxation was improved (non-transplanted control group: 82% ± 3%, transplanted control group: 14% ± 2%, aspirin group: 31% ± 4%, zinc-aspirin group: 52% ± 4%), the nitro-oxidative stress and cell apoptosis decreased, and significant endothelial protection was shown in the …

Frontiers in Cardiovascular Medicine

MethodsPatients with a BioMonitor IIIm and any device indication were included from three clinical projects. All subcutaneous ECGs (sECGs) transmitted via remote monitoring were classified by the algorithm as “true” or “false.” We quantified the relative reduction in workload assuming “false” sECGs were ignored. The remote monitoring workload from five hospitals with established remote monitoring routines was evaluated. Loss in sensitivity was estimated by testing a sample of 2000 sECGs against a clinical board of three physicians.ResultsOf our population of 368 patients, 42% had an indication for syncope or pre-syncope and 31% for cryptogenic stroke. Within 418.5 patient-years of follow-up, 143,096 remote monitoring transmissions contained 61,517 sECGs. SmartECG filtered 42.8% of all sECGs as “false,” reducing the number per patient-year from 147 to 84. In five hospitals, nine trained reviewers …

Frontiers in Cardiovascular Medicine

Revascularization completeness after percutaneous coronary intervention (PCI) is associated with improved long-term outcomes. Mechanical circulatory support [intra-aortic balloon pump (IABP) or Impella] is used during high-risk PCI (HR-PCI) to enhance peri-procedural safety and achieve more complete revascularization. The relationship between revascularization completeness [post-PCI residual SYNTAX Score (rSS)] and left ventricular ejection fraction (LVEF) in HR-PCI has not been established. We investigated LVEF predictors at 90 days post-PCI with Impella or IABP support. Individual patient data (IPD) were analyzed from PROTECT II (NCT00562016

Frontiers in Cardiovascular Medicine

Introduction Studies in cholesterol-fed rabbits showed that anti-proliferative chemotherapeutic agents such as paclitaxel associated with solid lipid nanoparticles (LDE) have marked anti-atherosclerotic effects. In addition, association with LDE nearly abolishes paclitaxel toxicity. We investigated whether treatment with LDE-paclitaxel changes plaque progression by coronary CT angiography and is safe in patients with chronic coronary artery disease. Methods We conducted a prospective, randomized, double-blind, placebo-controlled pilot study in patients with multi-vessel chronic coronary artery disease. Patients were randomized to receive IV infusions of LDE-paclitaxel (paclitaxel dose: 175 mg/m2 body surface) or LDE alone (placebo group), administered every 3 weeks for 18 weeks. All participants received guideline-directed medical therapy. Clinical and laboratory safety evaluations were made at baseline and every 3 weeks until the end of the study. Analysis of inflammatory biomarkers and coronary CTA was also performed at baseline and 4 weeks after treatment. Results Forty patients aged 65.6 ± 8 years, 20 in LDE-paclitaxel and 20 in placebo group were enrolled. Among those, 58% had diabetes, 50% had myocardial infarction, and 91% were in use of statin and aspirin. Baseline demographics, risk factors, and laboratory results were not different between groups. In all patients, no clinical or laboratory toxicities were observed. From the baseline to the end of follow-up, there was a non-significant trend toward a decrease in IL-6 levels and hsCRP in the LDE-paclitaxel group (−16% and −28%, respectively), not observed in placebo …

Frontiers in cardiovascular medicine

Background Surgery for type A aortic dissection (TAAD) is associated with high risk of mortality. Current risk scoring methods have a limited predictive accuracy. Methods Subjects were patients who underwent surgery for acute TAAD at 18 European centers of cardiac surgery from the European Registry of Type A Aortic Dissection (ERTAAD). Results Out of 3,902 patients included in the ERTAAD, 2,477 fulfilled the inclusion criteria. In the validation dataset (2,229 patients), the rate of in-hospital mortality was 18.4%. The rate of composite outcome (in-hospital death, stroke/global ischemia, dialysis, and/or acute heart failure) was 41.2%, and 10-year mortality rate was 47.0%. Logistic regression identified the following patient-related variables associated with an increased risk of in-hospital mortality [area under the curve (AUC), 0.755, 95% confidence interval (CI), 0.729–0.780; Brier score 0.128]: age; estimated glomerular filtration rate; arterial lactate; iatrogenic dissection; left ventricular ejection fraction ≤50%; invasive mechanical ventilation; cardiopulmonary resuscitation immediately before surgery; and cerebral, mesenteric, and peripheral malperfusion. The estimated risk score was associated with an increased risk of composite outcome (AUC, 0.689, 95% CI, 0.667–0.711) and of late mortality [hazard ratio (HR), 1.035, 95% CI, 1.031–1.038; Harrell's C 0.702; Somer's D 0.403]. In the validation dataset (248 patients), the in-hospital mortality rate was 16.1%, the composite outcome rate was 41.5%, and the 10-year mortality rate was 49.1%. The estimated risk score was predictive of in-hospital mortality (AUC, 0.703, 95% CI, 0.613–0.793; Brier …

Frontiers in Cardiovascular Medicine

ObjectivesThis study has been conducted to investigate the non-invasive diagnostic journey of patients with a transthyretin amyloid cardiomyopathy (aTTR-CM) in Turkey, identify the challenges and uncertainties encountered on the path to diagnosis from the perspectives of expert physicians, and develop recommendations that can be applied in such cases.MethodsThis study employed a three-round modified Delphi method and included 10 cardiologists and five nuclear medicine specialists. Two hematologists also shared their expert opinions on the survey results related to hematological tests during a final face-to-face discussion. A consensus was reached when 80% or more of the panel members marked the “agree/strongly agree” or “disagree/strongly disagree” option.ResultsThe panelists unanimously agreed that the aTTR-CM diagnosis could be established through scintigraphy (using either 99mTc-PYP …

Frontiers in Cardiovascular Medicine

Introduction More than 76,000 women die yearly from preeclampsia and hypertensive disorders of pregnancy. Early diagnosis and management of preeclampsia can improve outcomes for both mother and baby. In this study, we developed artificial intelligence models to detect and predict preeclampsia from electrocardiograms (ECGs) in point-of-care settings. Methods Ten-second 12-lead ECG data was obtained from two large health care settings: University of Tennessee Health Science Center (UTHSC) and Atrium Health Wake Forest Baptist (AHWFB). UTHSC data was split into 80% training and 20% holdout data. The model used a modified ResNet convolutional neural network, taking one-dimensional raw ECG signals comprising 12 channels as an input, to predict risk of preeclampsia. Sub-analyses were performed to assess the predictive accuracy for preeclampsia prediction within 30, 60, or 90 days before diagnosis. Results The UTHSC cohort included 904 ECGs from 759 females (78.8% African American) with a mean ± sd age of 27.3 ± 5.0 years. The AHWFB cohort included 817 ECGs from 141 females (45.4 African American) with a mean ± sd age of 27.4 ± 5.9 years. The cross-validated ECG-AI model yielded an AUC (95% CI) of 0.85 (0.77-0.93) on UTHSC holdout data, and an AUC (95% CI) of 0.81 (0.77-0.84) on AHWFB data. The sub-analysis of different time windows before preeclampsia prediction resulted in AUCs (95% CI) of 0.92 (0.84-1.00), 0.89 (0.81-0.98) and 0.90 (0.81-0.98) when tested on ECGs 30 days, 60 days and 90 days, respectively, before diagnosis. When assessed on early onset preeclampsia (preeclampsia …

Frontiers in Cardiovascular Medicine

Objective This study utilized computed tomography angiography (CTA) to assess the risk of acute type A aortic dissection (ATAAD) by analyzing the imaging morphology indicators of the ascending aorta, along with the relevant risk factors associated with aortic dissection. Methods The study utilized a retrospective observational research design. The population consisted of 172 patients who received treatment in the Department of Cardiothoracic Surgery at Qilu Hospital, Shandong University, from January 2018 to December 2022. The patients were divided into two groups: the ATAAD group (n = 97) and the thoracic aortic aneurysm group (TAA, n = 75). Demographic data and ascending aorta CTA measurements were collected from all patients. Single factor and multivariate logistic regression were employed to analyze the statistical differences in clinical data and ascending aorta CTA imaging morphology indicators between the two groups. Results The variables were included in logistic multivariate analysis for further screening, indicating that the length of the ascending aorta (LAA) before ATAAD (OR = 3.365; 95% CI :1.742–6.500, P<0.001), ascending arch angle (asc-arch angle, OR = 0.902; 95% CI: 0.816–0.996, P = 0.042) and the maximum aortic diameter (MAD) before ATAAD, (OR = 0.614; 95% CI: 0.507–0.743, P<0.001) showed statistically significant differences. Conclusions This study suggests that increased LAA and MAD, as well as a smaller asc-arch angle may be high-risk factors for the onset of ATAAD.

Frontiers in Cardiovascular Medicine

This editorial features the collection of articles published in Frontiers in Cardiovascular Medicine: Rising Stars 2021. The goal of this Research Topic is to promote the high-quality work of researchers at the early stages of their careers. The publications in this collection were selected based on their advancement in cardiovascular medicine and the research potential of the investigators. Here we celebrate the achievements of early-career investigators who thrive in the increasing hardships of academic research, including the fierce competition to secure research grant funding, and the publish-or-perish lifestyle of research dissemination (1). These rising stars possess determination, diligence, brilliance, and persistence—the qualities needed to survive the attrition rate and find success. The collection also represents the diversity of our scientific community. The following are the articles in the Frontiers in Cardiovascular Medicine: Rising Stars 2021 collection.Proinflammatory Matrix Metalloproteinase-1 Associates with Mitral Valve Leaflet Disruption Following Percutaneous Mitral Valvuloplasty, by Passos et al.. Mitral leaflet tearing is a serious and life-threatening complication of percutaneous mitral valvuloplasty (PMV). This original report demonstrates that pro-inflammatory factors such as MMP-1 and IFN-γ positively correlate with each other within valvular tissue and contribute to the localized degradation of collagen. Understanding the underlying mechanisms responsible for leaflet integrity disruption not only advances the fundamental insights into complications of PMV, but also is important for developing treatment strategies to treat mitral valve …

Frontiers in Cardiovascular Medicine

BackgroundArtificial intelligence (AI) has shown promise in the early detection of various cardiac conditions from a standard 12-lead electrocardiogram (ECG). However, the ability of AI to identify abnormalities from single-lead recordings across a range of pathological conditions remains to be systematically investigated. This study aims to assess the performance of a convolutional neural network (CNN) using a single-lead (D1) rather than a standard 12-lead setup for accurate identification of ECG abnormalities.MethodsWe designed and trained a lightweight CNN to identify 20 different cardiac abnormalities on ECGs, using data from the PTB-XL dataset. With a relatively simple architecture, the network was designed to accommodate different combinations of leads as input (< 100,000 learnable parameters). We compared various lead setups such as the standard 12-lead, D1 alone, and D1 paired with an …

Frontiers in Cardiovascular Medicine

Cardiac contractility modulation (CCM) is based on electrical stimulation of the heart without alteration of action potential and mechanical activation, the data on its fundamental molecular mechanisms are limited. Here we demonstrate clinical and physiological effect of 12 months CCM in 29 patients along with transcriptomic molecular data. Based on the CCM effect the patients were divided into two groups: responders (n = 13) and non-responders (n = 16). RNA-seq data were collected for 6 patients before and after CCM including 3 responders and 3 non-responders. The overall effect of CCM on gene expression was mainly provided by samples from the responder group and included the upregulation of the genes involved in the maintenance of proteostasis and mitochondrial structure and function. Using pathway enrichment analysis, we found that baseline myocardial tissue samples from responder group were characterized by upregulation of mitochondrial matrix-related genes, Z disc-protein encoding genes and muscle contraction-related genes. In summary, twelve months of ССM led to changes in signaling pathways associated with cellular respiration, apoptosis, and autophagy. The pattern of myocardial remodeling after CCM is associated with initial expression level of myocardial contractile proteins, adaptation reserves associated with mitochondria and low expression level of inflammatory molecules.

Frontiers in Cardiovascular Medicine

Introduction Pre-hypertension is a prevalent condition among the adult population worldwide. It is characterized by asymptomatic elevations in blood pressure beyond normal levels but not yet reaching the threshold for hypertension. If left uncontrolled, pre-hypertension can progress to hypertension, thereby increasing the risk of serious complications such as heart disease, stroke, kidney damage, and others. Objective The precise mechanisms driving the progression of hypertension remain unknown. Thus, identifying the metabolic changes associated with this condition can provide valuable insights into potential markers or pathways implicated in the development of hypertension. Methods In this study, we utilized untargeted metabolomics profiling, which examines over 1,000 metabolites to identify novel metabolites contributing to the progression from pre-hypertension to hypertension. Data were collected from 323 participants through Qatar Biobank. Results By comparing metabolic profiles between pre-hypertensive, hypertensive and normotensive individuals, six metabolites including stearidonate, hexadecadienoate, N6-carbamoylthreonyladenosine, 9 and 13-S-hydroxyoctadecadienoic acid (HODE), 2,3-dihydroxy-5-methylthio- 4-pentenoate (DMTPA), and linolenate were found to be associated with increased risk of hypertension, in both discovery and validation cohorts. Moreover, these metabolites showed a significant diagnostic performance with area under curve >0.7. Conclusion These findings suggest possible biomarkers that can predict the risk of progression from pre-hypertension to hypertension. This will aid in early detection …

Frontiers in Cardiovascular Medicine

Cardiovascular mortality is still excessively high, despite the considerable progress made in the prevention and treatment of cardiovascular diseases. Although many cardiovascular risk factors (such as arterial hypertension, hypercholesterolemia, diabetes, etc.), identified in the general population, are being promptly treated, to date little consideration is given to a cardiovascular risk factor which we believe has largely demonstrated in the scientific literature of the last three decades that, if neglected, can produce a series of relevant negative effects on the cardiovascular system: insulin resistance (IR)/hyperinsulinemia (Hyperins). This risk factor is still not sufficently sought in the general population and, consequently, is not treated promptly, as it should be, to avoid its negative impact on the cardiovascular system. IR's prevalence is constantly growing worldwide, and it is estimated to have reached a prevalence of 51% of the general population in developed and developing countries, and Hyperins is a constant and strong feature of IR. This article aims to stimulate the scientific community towards IR/Hyperins as relevant cardiovascular risk factor, since it is still neglected. The scientific literature analyzed and used to for this article was found on PubMed, Scopus, Science Direct, etc, using the following keywords: insulin, insulin signaling, insulin resistance, hyperinsulinemia, cardiovascular risk factors, cardiovascular system, cardiovascular diseases. We selected studies that explored the association between IR/Hyperins and the cardiovascular system, and those that discussed the possibilities of screening and treatment of IR/Hyperins.

Frontiers in Cardiovascular Medicine

MethodsPatients with a BioMonitor IIIm and any device indication were included from three clinical projects. All subcutaneous ECGs (sECGs) transmitted via remote monitoring were classified by the algorithm as “true” or “false.” We quantified the relative reduction in workload assuming “false” sECGs were ignored. The remote monitoring workload from five hospitals with established remote monitoring routines was evaluated. Loss in sensitivity was estimated by testing a sample of 2000 sECGs against a clinical board of three physicians.ResultsOf our population of 368 patients, 42% had an indication for syncope or pre-syncope and 31% for cryptogenic stroke. Within 418.5 patient-years of follow-up, 143,096 remote monitoring transmissions contained 61,517 sECGs. SmartECG filtered 42.8% of all sECGs as “false,” reducing the number per patient-year from 147 to 84. In five hospitals, nine trained reviewers …