bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMPACT OF HEAT–NOT–BURN CIGARETTE PASSIVE SMOKING ON CHILDREN‘S OXIDATIVE STRESS, ENDOTHELIAL AND PLATELET FUNCTION
Authors: Maggio E , Carnevale R , Pannunzio A , Cinicola B , Palumbo I , Bartimoccia S , Nocella C , Cammisotto V , Violi F , Biondi–Zoccai G , Frati G , Zicari A , Loffredo L 
Published: May 2024

Abstract
Growing global use of heat–not–burn cigarettes (HNBC) prompts investigation. Prior studies assessed HNBC‘s effects on cardiovascular health, revealing heightened oxidative stress, platelet activation, and endothelial dysfunction. However, limited understanding exists regarding passive smoking‘s impact on children exposed to HNBC.
This study aims to assess levels of oxidative stress, endothelial and platelet function among children exposed to passive smoke from HNBC, traditional tobacco (TT) cigarettes and unexposed subjects. Seventy–eight children (2–18 years) were divided into three groups: HNBC passive smokers (n=26), TT cigarette exposed (n=26), and control (CNT) group (n=26, unexposed).
Oxidative stress was evaluated by serum NADPH oxidase–2 (NOX2) activity, assessed by soluble Nox2–derived peptide (sNOX2–dp), isoprostanes, hydrogen peroxide (H2O2) production, hydrogen break–down activity (HBA) and NO bioavailability. Endothelial function was assessed by brachial flow–mediated dilation (FMD). Platelet function was evaluated by soluble CD40 ligand (sCD40L), soluble P–selectin (sP–selectin) and thrombus formation by T–TAS analysis. Passive smoking–exposed children (both HNBC and TT) exhibited significantly increased serum sNOX2–dp, isoprostanes, H2O2, sCD40L sP–selectin and thrombus formation versus controls. Conversely, exposed children displayed reduced brachial FMD and serum NO bioavailability. No significant differences were found between children exposed to passive smoking of HNBC vs TT.
Multivariable regression linked sNOX2 (standardized coefﬁcient β:–0.284; SE: 0.040; p=0.01) and H2O2 (standardized coefﬁcient β:–0.243; SE: 0.0; p=0.02) as independent predictors of FMD, and isoprostanes (standardized coefﬁcient β:0.388; SE: 0.022; p&lt;0.001) and serum cotinine (standardized coefﬁcient β:0.270; SE: 0.048; p=0.01) with sNOX2–dp levels.
Exposure to HNBC smoke heightened oxidative stress, endothelial dysfunction, platelet activation, and thrombus formation in children. Findings suggest avenues for interventions to curb childhood passive smoking exposure.
SEX DIFFERENCES IN CLINICAL CHARACTERISTICS AND OUTCOMES OF PATIENTS UNDERGOING CATHETER–DIRECTED TREATMENTS FOR HIGH RISK AND INTERMEDIATE–HIGH RISK ACUTE PULMONARY EMBOLISM. DO WE NEED SEX–SPECIFIC CONSIDERATIONS IN THE MANAGEMENT OF ACUTE PE?
Authors: Morosato M , Russo F , Iannaccone M , Colombo C , Adamo M , Galli M , Boccuzzi G , Bossi I , Nicolò C , Ferri L , Giuliano C , Rampoldi A , De Nittis G , Montorfano M , Oliva F , Chieffo A , Sacco A 
Published: May 2024

Abstract

Background
Acute pulmonary embolism (PE) is a common disease associated with a high mortality rate. Catheter–Directed Treatments (CDTs) could address some unsolved issues in high and intermediate–high risk PE patients evolving towards hemodynamic deterioration when systemic thrombolysis (ST) is contraindicated or fails. Few data in literature suggest that female patients hospitalized for PE experience adverse clinical outcomes as compared with their male counterparts. However, whether there is a specific impact of sex on CDTs outcomes in PE within real–world clinical settings remains unexplored.

Methods
This is a multicenter retrospective study including patients admitted in five Italian Centers, who underwent CDTs for high and intermediate–high risk PE, as defined by ESC Guidelines. In–hospital and one–year clinical outcomes were evaluated using medical records and follow–up assessments. Bleeding events were defined according to the Bleeding Academic Research Consortium (BARC) criteria.

Results
A total of 191 patients were included, 101 women (52.9%) and 90 men (47.1%). High risk PE was diagnosed in 56 (29%) patients, while intermediate–high risk PE was diagnosed in 135 (71%). Of these, 132 (69%) were treated by ultrasound–assisted thrombolysis (USAT), with negligible sex disparity between treatment modalities. Notably, female patients presented more frequently with cardiac arrest (11% vs. 2.6%, p = 0.03), had lower prevalence of absolute contraindications to ST (23% vs. 42%, p = 0.004) and history of recent major surgery (8.9% vs. 22%, p = 0.01). Female patients had a trend towards higher procedural–related complications (17% versus 9%, OR 2.07 95%CI 0.87–5.33, p=0.11), higher in–hospital mortality rate (20% versus 8.9%, OR 2.53 95%C.I. 1.09–6.41, p=0.038) and higher likelihood of bleeding events (22% versus 10%, OR 2.54 95%CI 1.13–6.14, p=0.029). At 1 year follow–up, female sex was associated with higher all–cause mortality (29.1% versus 12.7%, HR 2.50 95%CI 1.15–5.43, p=0.022). Multivariate regression analysis identified female sex, diagnosis of high–risk PE and a history of neoplasia as independent predictors of 1–year all–cause mortality.

Conclusions
In our experience, female patients undergoing CDTs for acute PE showed worse clinical presentation, higher procedural–related complications, and poorer outcomes than males. In our opinion this sex disparity underscores the need for sex–specific considerations in acute PE management strategies.
SOLUBLE GUANYLATE CYCLASE ACTIVATOR VERICIGUAT PREVENTS ANTHRACYCLINE–MEDIATED CARDIOTOXICITY AND SARCOPENIA THROUGH NO–SGC–CGMP–NLRP3 PATHWAY: POTENTIAL APPLICATION IN CANCER PATIENTS
Authors: Quagliariello V , Iovine M , Giacobbe I , Giordano V , Arianna R , Barbato M , Izzo F , Maurea F , Bisceglia I , Paccone A , Inno A , Maurea N 
Published: May 2024

Abstract

Background
Anthracycline–induced cardiomyopathies and sarcopenia are frequently seen in cancer patients, affecting their overall survival and quality of life; therefore, new cardioprotective strategies are needed in cardioncology. Vericiguat is a new oral guanylate cyclase activator that reduces heart failure hospitalizations or cardiovascular death through improvement of smooth muscle cell relaxation and reduction of myocardial fibrosis and inflammation. In this study, we highlight on the potential cardioprotective properties of vericiguat against anthracycline.mediated cardiotoxicity and sarcopenia.

Methods
Human cardiomyocytes (AC–16 cells) and Primary Skeletal Muscle Cells (HSkMC cells) were exposed for 48h to doxorubicin (DOXO) at 0,3 and 1 µM or Vericiguat at 10–7,10–5,10–3 mM or both in combination. Mithocondrial cell viability, LDH and Citocrome C release were performed to study cytoprotective properties. TUNEL assay, cGMP and NLRP–3, Myd–88 intracellular levels were quantified through colorimetric and selective ELISA methods. IL–1β, IL–6, IL–8, CXCL–2, TGF–β and IL–18 were also analyzed in cardiac and muscle cell lysates after treatments.

Results
Vericiguat exerts a significant cytoprotective and anti–apoptotic effect in cardiac and muscle cell lines during exposure to DOXO. A drastic increase in cGMP expression and reduction in NLRP–3, Myd–88 levels were also seen in Vericiguat–DOXO groups vs DOXO groups (p&lt;0.001). Pro–inflammatory and cytotoxic cytokines were also downregulated after Vericiguat treatment during DOXO exposure.

Conclusions
Vericiguat significantly reduced cardiotoxic effects and sarcopenia induced by DOXO therapy though enhancement of cGMP levels and reduction of NLRP–3/Myd–88/cytokines pathways. These findings provide a framework for future studies aiming to assess vericiguat for the therapeutic targeting of anthracycline–mediated cardiotoxicity and sarcopenia.
A CASE OF RIGHT HEART FAILURE: WHEN IT IS NOT PULMONARY EMBOLISM
Authors: Tadiello E , Zimelli E , Urbani G , Hinna Danesi T , Reghellin D , Bilato C 
Published: May 2024

Abstract
A 66–year–old patient, showing exertional dyspnea and atypical chest pain, came to our attention with instrumental findings at echocardiogram of right ventricular failure and was hospitalized due to worsening signs and symptoms of right heart failure. Signs of right ventricular strain and the McGinn–White sign (S1Q3T3 pattern) were seen on the ECG, leading to the suspicion of pulmonary thromboembolism (PE). Pulmonary CT angiography confirmed bilateral PE involving the main pulmonary artery. Oral anticoagulant therapy was initiated with initial partial benefit and relief of symptoms. However, after four weeks, the patient was readmitted for severe heart failure and signs of low cardiac output. Echocardiography showed the presence of a conspicuous, mobile, isoechoic mass occupying most of the main pulmonary artery, suggesting thrombosis. The patient underwent urgent surgical thromboendoarterectomy extended to the third segmental left branches and to the second segmental right branches of the pulmonary artery; a severe pulmonary valve regurgitation was observed and therefore the valve was replaced with a Edwards–Magna pericardial bioprosthetic valve. ECMO (Extracorporeal Membrane Oxygenation) was initiated due to haemodinac instability. In the postoperative period, the severe heart failure worsened, unresponsive to pharmacological treatments and mechanical support, leading to the patient passing away in the following days. Unexpectedly, histological analysis of the surgical specimen revealed neoplastic cells with vascular/endothelial differentiation; fluorescence in situ hybridization (FISH) detected the MDM2 gene (cfr.23–F–00275), involved in the p53 protein regulation mechanisms, which is consistent with a diagnosis of angiosarcoma. Pulmonary–artery angiosarcomas are extremely rare (few anecdotical cases are described in literature) and resemble the CT–signs and clinical features of PE, seriously delaying the diagnosis. They are usually associated with a worse prognosis than PE, one and a half months survival time when inoperable. Radical surgery, associated with thirty six and a half months survival time, is often unfeasible because of locally advanced disease or metastatic disease already present at diagnosis. The main differences with PE are the more proximal and almost–occluding involvement of the pulmonary artery, the absence of peripheral vein thrombosis and the absence of response to anticoagulant therapy.
TWO LEADS IN ONE CORONARY SINUS: A RARE CASE OF TRANSVENOUS LEAD EXTRACTION
Authors: Arabia G , Cerini M , Calvi E , Falco R , Bellicini M , Nicolai A , Curnis A 
Published: May 2024

Abstract
Device–related infection remains a potentially fatal complication in patients with cardiac implantable electronic devices (CIEDs). Current guidelines recommend complete system extraction in such cases. Moreover, lead extraction of multiple leads implanted in the same CS tributary can be challenging. We describe a case of 71–year–old male with dilated cardiomyopathy. He underwent an implantable cardioverter defibrillator (ICD) implantation in secondary prevention in the year 2005, after a previous cardiac arrest. Subsequently, an upgrading to a cardiac resynchronization therapy defibrillator (CRT–D) in 2018 was performed with a unipolar coronary sinus lead implanted in an anterolateral branch of the coronary sinus (CS). Two months a new active fixation lead was implanted in CS for an elevated impedance of the previous CS catheter. In February 2022, the patient presented signs of pocket infection and was referred to our center for transvenous lead extraction (TLE). For the coronary sinus leads, a locking stylet was first positioned in each lead, then mechanical sheaths were advanced over the passive lead and subsequently on the active lead. Afterwards, a hand–powered mechanical sheath was advanced sequentially over each lead up to the coronary sinus ostium. Contrast injection through the sheath revealed extensive fibrosis of the CS ostium. Midline sternotomy was done and through a right atrial incision, the proximal parts of the CS leads were externalized. A 7.5 Fr mechanical dilator sheath was then advanced over the passive lead, allowing the removal of both the CS leads. Upon resolution of the infection, a new CRT–D device was implanted with two leads in the right ventricle (one in the right ventricular apex, and the other on the interventricular septum), following a multisite right ventricular pacing approach. We present the first case in literature to undergo lead extraction of two leads in the same coronary coronary sinus. The presence of two leads induced extensive fibrosis inside the CS. A combination with surgical approach was needed in order to avoid any possible tear of the coronary sinus. The unusual implantation of more than one lead in the same CS tributary can increase the procedural risk when the need for extraction arises. In that case, a surgical approach combined with the utilization of transvenous lead extaction tools can provide a way to extract the leads with minimal surgical manipulation.
WHEN AND WHERE DOES A CARRIER OF HEREDITARY TRANSTHYRETIN AMYLOIDOSIS (ILE88LEU) SHOW THE FIRST SIGNS OF THE DISEASE? DIAGNOSTIC CHALLENGES OF A NOT ONLY CARDIOGENIC MUTATION
Authors: Brugiatelli L , Vagnarelli F , Lofiego C , Capodaglio I , Patani F , Tofoni P , Maurizi K , Pietrucci F , Schicchi N , Tortora G , Lupidi F , Burroni L , Dello Russo A , Perna G 
Published: May 2024

Abstract
We present the case of a 58–year–old man with a familiar history (mother affected) positive for ATTR–v (Ile88Leu) amyloidosis. The mother initially had a pure cardiac phenotype and was firstly treated with tafamidis, but progression of the disease to the nervous system warranted a switch to patisiran. Our patient carried the Ile88Leu mutation and had a medical history notable for surgically treated left carpal tunnel syndrome (CTS) and untreated right CTS. Furthermore, he was affected by systemic arterial hypertension and was a habitual smoker. He has been followed at our Institution since 2018. His first echocardiogram showed normal left ventricular ejection fraction (LVEF 65%), mild hypertrophy (anterior septum: 12 mm), and borderline values of GLS (– 16%) without any specific pattern. Further exams were executed: Bone scintigraphy (BS): negative (Perugini score 0); Coronary artery ct scan: moderate stenosis of proximal LAD; Neurologic evaluation: no signs of peripheral neuropathy. The clinical picture remained unaltered in 2020 and 2021. However, during November 2022 the patient developed atrial fibrillation (AF) and presented to the ED for dyspnea and palpitations. Electrical cardioversion was performed with success but subsequent recurrences warranted AF ablation in April 2023. At that moment, the patient was re–evaluated. Basal ECG did not show any significant alteration (FIg.1)This time, echocardiogram showed mild worsening of hypertrophy (13 mm septum), GLS – 16% with apical sparing pattern, no other major variations (Fig.2). BS was repeated and revealed grade 1 Perugini score (Fig.3). Hence, a series of clinical question arose: Should we begin a specific treatment or is the disease in an excessively early stage that does not warrant treatment? Is AF linked to concomitant arterial hypertension or might it be an early marker of disease? We questioned the usefulness of endomyocardial biopsy in this specific setting. In this case, we repeated electromyography that showed mild axonal sensitive–motor polyneuropathy. Finally, we concluded for initial signs of systemic amyloidosis ATTR–v (Ile88Leu) type with mixed phenotype (neurological+cardiac). The neurological involvement allowed us to start a gene–silencer (Patisiran). In conclusion, a periodic neurological evaluation is necessary and has crucial therapeutic implications in all genotypes. Indeed, there is increasing evidence that Ile88Leu is a not only cardiogenic mutation.
DON’T FORGET ABOUT CARDIAC AMYLOIDOSIS: WHEN RED FLAGS MATTER
Authors: Pedio E , Colucci C , Falagario A , Mannarini A , De Michele L , D‘Agostino C 
Published: May 2024

Abstract

Case Report
A 78–year–old man came to our attention for worsening dyspnea, asthenia and frequent lipothymic episodes in the last few weeks. Nothing remarkable was reported in anamnesis except for periodic cardiological check–ups ascribed to hypertensive heart disease and moderate aortic stenosis. Other cardiovascular risk factors were obesity, previous smoking habits and dyslipidemia. A recent 24–hours ECG monitoring revealed slow permanent atrial fibrillation (AF) with 3–seconds pauses, frequent premature ventricular complexes (PVCs) and some PVCs couplets. On arrival, NT–proBNP was elevated (2952 pg/mL), while ECG showed AF with a heart rate of 50/m and low voltages in peripheral leads. Transthoracic echocardiogram revealed a biatrial dilatation, a severe left ventricular (LV) concentric hypertrophy with a preserved LV ejection fraction (EF) and a moderate aortic stenosis. In addition, a restrictive LV filling pattern, a decreased longitudinal myocardial contraction and an apical sparing of longitudinal strain were reported. Invasive coronary angiography was performed with evidence of normal coronary arteries. Given the echocardiographic suspicion of amyloidosis, a 99mTc–Hydroxymethylene diphosphonate (HMDP) scintigraphy was performed, showing a moderate cardiac uptake and an attenuated bone uptake (Perugini Score 2). Serum and urine immunofixation resulted negative. Genetic testing did not find any mutations in Transthyretin (TTR) gene. Therefore, the diagnosis of TTR wild–type amyloidosis was made. Before discharge, putting it all together, we opted to implant a leadless pacemaker in order to protect the patient from life–threatening bradyarrhythmias.

Discussion
Although it is currently considered rare, there is growing evidence that cardiac amyloidosis may be more common than once thought. First of all, it should be investigated in HFpEF–patients (heart failure with preserved EF) with LV hypertrophy. Despite several red flags (low QRS voltages, conduction disorders, elevated NT–proBNP, severe LV hypertrophy and aortic stenosis) and various medical consultations, our patient had to wait 4 years or more to be diagnosed with cardiac amyloidosis. Inevitably, a diagnostic delay means loss of time in treatment initiation. Earlier diagnosis would enable us to improve our patients’ survival and heart failure hospitalization. Awareness alone is not enough, we must be right on target too.
COMPARISON BETWEEN DIFFERENT TRANSRADIAL ARTERY HEMOSTASIS PROTOCOLS IN LIGURIAN CARDIOLOGIES
Authors: Lorenzo P , Corona M 
Published: May 2024

Abstract

Background
Transradial artery access (TRA) for coronary angiography and percutaneous coronary intervention is associated with lower bleeding and vascular complications than transfemoral artery access. In our hospital, TRA is widely used and hemostasis is usually achieved using TRBand device. We used to remove the device in about 10 hours according to our protocol.

Aims
The aim of this study is to describe and compare different TRA hemostasis protocols in order to understand if a shorter protocol could be more effective.

Methods
This is an observational study performed in all Hospitals of our region (Liguria). All Cardiology Departments were included in this analysis. We requested to all to self–refer: a) which radial hemostasis device was used; b) which deflation protocol (DP) was used. c) If they usually report and analyze adverse events. Adverse events are described as: bleeding, hematoma, ecchymosis, skin damage, local infection, pseudoaneurysm, or artery occlusion. RESULTS In Liguria there are 9 Cardiology Departments with Cath Lab (CL); 8 of them accepted to participate. All the Cath Labs use the TRBAND device but the deflation protocols are very different. 5 Cath Labs follows the DP suggested by the manufacturer. Only 2 CL adopted different DP if and higher dose of heparin was administered. Only one report bleedings or any delete in the DP. None analyze periodically the incidence of adverse events.

Conclusions
There are different methods to achieve radial hemostasis furthermore with the same device different deflating protocols are used. Further studies are necessary to evaluate the best DP. Regular audits must be strongly suggested in all Cardiology Departments in order to monitorate and improve the adverse events.
LASER CORONARY ATHERECTOMY AND POLYMERIC CORONARY WIRES IN UNCROSSABLE LESIONS – A WORD OF CAUTION
Authors: Marengo G , Amat Santos I , De Benedictis M , Barbero U , Doronzo M , Moncalvo C 
Published: May 2024

Abstract

Background
Excimer laser coronary atherectomy (ELCA) represents one of the last available options in case of balloon uncrossable lesions but no bench testing or clinical experience has been reported with polymeric wires. We aimed to assess whether ECLA use can disrupt or melt the cover and coating of coronary wires.

Methods
A total of 22 wires (10 polymer–jacketed and 12 hydrophilic non polymeric) were tested in an uncrossable lesion model. Two ELCA tests were performed over each wire at 8 and 4 cms from the tip with low and high settings, respectively. Microscopic analysis was performed at baseline images and after each test. Wire disruption was classified as Grade 1 (superficial scratches), Grade 2 (coil damage or solution of continuity of the polymeric cover) and Grade 3 (wire rupture/core disruption or de–coiling).

Results
After 44 ELCA simulations, wire disruption occurred in 16 cases (36.3%). Overall, events were more common for polymer–jacketed than for hydrophilic wires (12 vs 4, p=0.004). No grade 3 events occurred. Grade 2 events occurred in 9 cases (20.5%) and were more frequent with polymer–jacketed wires (8 vs 1, p=0.006). With low ELCA settings only polymer–jacketed wires suffered disruption (5 vs 0, p=0.009). With higher settings 11 events occurred (7 of Grade 2 and 4 of Grade 1) and incidence of grade 2 events was higher for polymer–jacketed wires (6 vs 1, p=0.02).

Conclusions
ELCA might be a safe option for coronary uncrossable lesions but its use with high settings over polymer–jacketed wires is discouraged.