bluuebunny/crossref_metadata_2025_split huggingface dataset:
689 Hybrid transvenous and surgical approach for the extraction of coronary sinus leads: a case series
Authors: Ahmed Ashraf , Arabia Gianmarco , Bontempi Luca , Cerini Manuel , Salghetti Francesca , Mitacchione Gianfranco , Milidoni Antonino , Stretti Lorenzo , Bernardi Nicola , Pezzola Elisa , Cimino Giuliana , Saccani Nicola , Curnis Antonio 
Published: December 2021

Abstract

Aims
The rates of cardiac device-related infection have increased substantially over the past years. Transvenous lead extraction is the standard therapy for such cases. In some patients, however, the procedure cannot be completed through the transvenous route alone. A hybrid surgical and transvenous approach may provide the solution in such cases.

Methods and results
We present three cases who underwent hybird transvenous and surgical extraction for coronary sinus leads due to infection of CRT-D systems. One patient had an Attain Starfix lead implanted in the coronary sinus. The procedures were performed under local anaesthesia with continuous haemodynamic and transthoracic echocardiographic monitoring. We highlight the characteristics of the patients, the features of the devices, the technical difficulties, and the outcomes of the procedures. In all cases, the right atrial and right ventricular leads were extracted through the transvenous route. In one patient, they were extracted using regular stylets and manual traction, while in the other two patients, telescoping dilator sheaths (Cook), Tightrail hand-powered mechanical sheaths (Spectranetics), and/or Glidelight Excimer Laser sheaths (Spectranetics) were used. The coronary sinus lead could not be retrieved due to extensive fibrosis after utilizing locking stylets and mechanical dilator sheaths in all three cases, in addition to rotational mechanical sheaths and laser sheaths in one case, so the patients were referred to surgery. Two patients underwent left mini-thoracotomy and one patient underwent midline sternotomy to extract the remaining CS lead. The target vein was identified and ligated, then the fibrosis around the lead was dissected, this was followed by lead retrieval through the surgical incision. The patient who underwent sternotomy suffered from mediastinitis, which required reoperation and mediastinal lavage. There were no complications in the other two patients. All three patients were reimplanted with a new CRT-D device on the contralateral side after the resolution of infection.

Conclusions
A hybrid surgical and transvenous approach can be complementary in case the transvenous route alone fails to completely extract the coronary sinus lead. The transvenous approach can be used to free the proximal part of the lead, while the distal adhesions can be removed surgically, preferably though a limited thoracic incision.
525 Incidence and possible determinants of device-pocket haematoma after cardiac implantable electronic devices in patients treated with a pressure dressing
Authors: Patti Alessandro , Santoro Francesco , Pellegrino Pierluigi , D’Arienzo Girolamo , Gianfrancesco Domenico , Bartolomucci Francesco , Brunetti Natale Daniele 
Published: December 2021

Abstract

Aims
Device-pocket haematoma (DPH) occurs in 2–15% of the implantations of cardiac rhythm devices. Major bleedings occur in 0.2–2% of the cases. The present study aims to evaluate the incidence of DPH in patients treated with a pressure dressing after implantation of a pacemaker and to investigate the impact of antiplatelet and anticoagulant therapy on DPH in the same cohort.

Methods and results
A retrospective evaluation on 446 consecutive patients who underwent implantation or replacement of pacemaker/ICD between 2017 and 2018 was performed. Cardiovascular risk factors, clinical parameters, medical history of the patients, as well as their drug history were collected. The presence or absence of perioperative DPH was investigated. All patients were treated with a pressure dressing immediately after the procedure and for the first 24 h. The preliminary results obtained after reviewing the medical records of the 446 patients (age 76.8 ± 10.4 years; 67% males; left ventricular ejection fraction 47.3 ± 12.2%) show an incidence of DPH of 8.1% (n = 36). 332 (74%) of the patients had documented hypertension, 131 (29%) diabetes, 213 (48%) were taking antiplatelet medications, and 150 (34%) were taking anticoagulants. No significant differences were found directly comparing the main variables under study between patients who experienced DPH and those who did not. However, at binomial logistic regression analysis, performed including antithrombotic therapies, sex, and age, a tendency of patients treated with warfarin to experience DPH emerged (OR : 3.25, 95% CI : 1.00–10.50; P = 0.049).

Conclusions
The preliminary results of the present study show an incidence of DPH of 8.1% in patients treated with a pressure dressing after pacemaker implantation. Between antithrombotic therapies, sex and age, anticoagulation therapy with warfarin appeared to be correlated with an increased risk of DPH.
547 Supernormal conduction of an accessory pathway: the case of a young sportsman
Authors: Robles Antonio Gianluca , Petrungaro Mattia , Penco Maria , Romano Silvio , Sciarra Luigi 
Published: December 2021

Abstract

Aims
Ventricular pre-excitation is defined by the presence of all of the following electrocardiographic criteria: PQ interval duration ≤120 ms, QRS duration ≥120 ms, and presence of δ wave (defined as initial ‘slurring’ of the QRS complex). Ventricular pre-excitation together with the presence of symptoms (orthodromic and/or antidromic atrioventricular reentry tachycardia, atrial fibrillation) defines Wolff–Parkinson–White (WPW) syndrome. The anatomical substrate of ventricular pre-excitation consists of an extranodal accessory atrio-ventricular connection: the so-called Kent bundle. Such pathways can have antegrade, retrograde, or mixed conductive properties. Accessory pathways endowed with anterograde conductive capability may be responsible for manifest, intermittent, or non-manifest ventricular pre-excitation depending on whether it is respectively always visible on the ECG, not always visible on the ECG and not visible on the ECG even though the pathway has the ability to antegrade conduction. The rare phenomenon of supernormal conduction of anomalous pathways is part of the manifest pre-excitation, which represents the topic of the case reported below.

Methods and results
We report the clinical case of a young not agonist sportsman undergoing an electrophysiological study (SEF) because of he is suffering from ventricular pre-excitation. The SEF did not showed the inducibility of arrhythmias and, at the same time, apparently it showed low risk characteristics of the pathway even during adrenergic stimulus. However, a careful study, performed with atrial stimulation with couplings up to refractoriness of the atrioventricular node revealed supernormal conduction properties of the Kent bundle which proved to have high risk characteristics according to current guidelines and, therefore, was effectively treated with catheter ablation.

Conclusions
This case invites us to careful studying of accessory pathways properties, especially since, although rare, they may possess supernormal conduction characteristics capable of determining high ventricular rates in the case of sustained atrial tachyarrhythmias, especially in conditions of adrenergic hyperactivity.
179 ICD or not ICD? A difficult choice for a young patient presenting with palpitations in emergency department
Authors: Savo Maria Teresa , Balducci Elisa , Calzolari Vittorio , Cernetti Carlo 
Published: December 2021

Abstract
A fit-and-well 52-year-old worker, with negative familiar story, was admitted to Emergency Department (ED) with haemodynamically unstable but well bore broad complex tachycardia of 180 b.p.m. (Figure 1). Twenty years before the patient had heart-surgery to repair atrial septal venous sinus defect with patch. The defect determined anomalous pulmonary venous return in right atrium with left to right shunt and moderate pulmonary hypertension. The surgery, 20 years before, was complicated by a single event of supraventricular tachycardia pharmacology resolved. Next follow-up was normal although at transthoracic echocardiography severe right ventricular (RV) dilation was reported. In the ED the patient had palpitation but not chest pain or dyspnoea. General clinical examination was normal but he was hypertensive (170/137 mmHg) and with heart rate of 180 b.p.m. Valsalva manoeuver was performed and adenosine (6 mg–12 mg–12 mg) was administered without benefit. Eventually, the patient was cardioverted to sinus rhythm with a single 100 J shock. His baseline ECG (Figure 2) showed sinus rhythm, normal axis, as well as right bundle branch block and T-wave inversion in leads V1–V4 and a waves with a small spike upward in lead V1 which represent characteristic epsilon waves.
Successively patient was admitted to Cardiology Department where transthoracic echocardiography showed severe RV dilation and moderate hypokinesia with a tricuspid annular plane excursion of 15 mm, TAV 9.6 cm/s, fractional area change of 29%. The right atrium was moderate dilated (volume 70 ml, indexed volume 35.53 ml/m2). Left chambers were normal. No shunts were observed. An electrophysiology study with isoprenaline infusion was performed but no arrhythmias were induced. Cardiac magnetic resonance imaging (MRI) was normal save for global RV dilatation, increased RV end diastolic volume (156 ml/m2), and global RV systolic dysfunction (reduction of RV ejection fraction 31%). Arrhythmogenic cardiomyopathy was excluded as patient’s background suggested RV dilation was due the overload caused by the history of left–right shunt. Blood tests and personal history negative initially exclude myocarditis and cardiac MRI confirmed the absence of oedema. An accurate ECG analysis excluded Brugada syndrome. Following discussion between electrophysiologists, clinical cardiologists, and the patient who first need to be informed, trans-venous ICD was implanted. 179 Figure 1ECG in ED.               Figure 2 Baseline ECG.                 Figure 3 Cardiac MRI.
93 Melatonin and oxidative stress in the prevention of cardiovascular disease
Authors: Cersosimo Angelica , Franco Caterina , Sciatti Edoardo , Favero Gaia , Vizzardi Enrico , Rezzani Rita 
Published: December 2021

Abstract

Aims
Arterial hypertension, especially if not well-controlled, is one of the main risk factors predisposing to fatal cardiovascular diseases (CVDs). Moreover, the diagnosis of essential hypertension are increasing, therefore oxidative stress and chronic inflammation have also been identified as potential responsible for the development of endothelial damage. Among all the molecules, melatonin (MT) was chosen for its role as a powerful antioxidant and anti-inflammatory endogenous molecule. This trial aims to evaluate the early intervention at the base of the inflammatory and oxidative cascade (that results in the development of hypertension), to restore an oxidative balance leading to positive results even at the endothelial and vascular level using MT in addition to anti-hypertensive therapy.

Methods
The trial is randomized, prospective and monocentric control. We enrolled 23 patients with hypertension in absence of other cardiovascular or autoimmune diseases that could alter the oxidative background, from March 2018 to April 2019 (recruitment period). Patients were randomly assigned to two groups: ‘melatonin group’ (in which 16 patients add 1 mg/day of melatonin for a year, to their already settled therapy), and a ‘control’ group (consisting of 7 patients with no changes in their therapy). The average follow-up was 1 year from randomisation. Patients were evaluated before and after a period of 1 year through MT plasma concentration and serum antioxidant capacity (TAC) by specific quantitative ELISA method. Therefore endothelial dysfunction and arterial stiffness were evaluated too (using the non-invasive methods of EndoPAT and SphygmoCor).

Results
In ‘melatonin group’ arterial stiffness index statistically decreased (P 0.022), according to a significant increase in plasma melatonin values (P 0.003) and significant decrease in TAC levels (P 0.041) despite the ‘control’ group. The improvement of endothelial function was not significant (P 0.688). Blood pressure had not a significative improvement too (P 0.401).

Conclusions
Data obtained could confirm the hypothesis of activation of plasma antioxidant system against a situation of altered oxidative balance. In fact, it is possible to hypothesize a correlation between TAC and arterial stiffness that confirm the antioxidant role of MT. The combination between antihypertensive therapy and antioxidant supplementation is able to improve the vascular stiffness. Data obtained are still preliminary and present some limitations but we can think of proposing this trial as a future basis for other extensive and prolonged studies.
306 Involvement of toll-like receptor 4 in PCSK9-mediated biological effects in cell culture models
Authors: Scalise Valentina , Sanguinetti Chiara , Lai Michele , Neri Tommaso , Celi Alessandro , Pedrinelli Roberto 
Published: December 2021

Abstract

Aims
The link between pro-protein convertase subtilisin/kexin 9 (PCSK9) and inflammatory-related disease was supported in several experimental and human studies, which show how the protein could acts independent its canonical mechanism, by activation of inflammatory, apoptotic and immune pathways. Among these, TLR4/NFKB signalling pathway was found to be one of the main pathways mediating the PCSK9-induced increase of pro-inflammatory and pro-thrombotic molecules, such as TNF-alpha, IL-6, IL-1, MCP-1, and TF. To investigate the direct involvement of hTLR4 in recognition of exogenous human recombinant (hr) PCSK9.

Methods
Experiments were carried out in three cell line: (i) HEK293-hTLR4-GFP cell lines obtained by stable co-transfection of HEK293 cells with the pUNO1-hTLR4-GFP, a plasmid expressing the hTLR4 gene fused to a GFP gene; (ii) HEK293-hTLR4+ cells obtained by co-transfection of hTLR4 receptor and its accessory proteins MD-2 and CD14, and an inducible secreted embryonic alkaline phosphatase (SEAP) reporter gene; (iii) HEK293-Null2 cells, a cell line lacking TLR4 expression, used as negative control. NFkB activity were measured by the SEAP reporter gene assay using a fluorescence detection method, while localization of hTLR4 and exogenous hrPCSK9 by confocal microscopy.

Results
hrPCSK9 (1 µg/mL) activates NFkB in HEK293-hTLR4+ cells [SEAP activity-OD 620 nm: from a baseline of 0.18 ± 0.06 to 0.68 ± 0.05 (N = 8), P &lt; 0.001] to an extent comparable to Lipopolysaccharide (LPS), the specific agonist of TLR4. Colocalization of hrPCSK9 and TLR4s was clearly documented by quantitative confocal microscopy in HEK293-hTLR4-GFP cell line, that comprises the analysis of more than 80 fields in ∼2.105 cells/well and showing a percentage of co-localization of ∼4% in membrane spots (P &lt; 0.01).

Conclusions
Our data support the results reported in previous studies that attribute to PCSK9 a pathophysiological role in development of chronic inflammation and related-diseases such as atherothrombosis. A behaviour that extends far beyond LDLR degradation, via a mechanism that might be mediated at least in part by recognition of PCSK9 by the TLRs and later activation of NFKB intracellular pathway. Future studies will be important to better investigate the specific binding site engaged in the PCSK9-TLR interaction and to discriminate the intracellular transduction pathways involved in this response, in order to provide a theoretical basis for the development of innovative therapeutic strategies.
682 Cardioncology: is it time to spread the need for dedicated management?
Authors: Magnesa Michele , Casavecchia Grazia , Barone Roberta , Riccardo Mariolina , Corbo Delia , Brunetti Natale Daniele 
Published: December 2021

Abstract

Case report
A 56-year-old man affected by micromolecular multiple myeloma was treated by several cycles of different chemotherapy drugs from September 2015 to December 2020. The chemotherapy regimen included 4-cycle first-line therapy with Bortezomib, Thalidomide, and Dexamethasone; 19-cycle second-line therapy with Carfilzomib, Revlimid, and Dexamethasone; 8-cycle third-line therapy with Daratumumab, Revlimid, and Dexamethasone; finally, he was started on therapy with Pomalidomide and Endoxan. During the various treatments, the patient did not follow a dedicated cardiological follow-up programme. In November 2020, he was hospitalized in the Intensive Care Unit for acute pulmonary oedema and subsequently discharged with a diagnosis of mild left ventricular systolic dysfunction (LVEF 50%). One month later, due to the worsening of dyspnoea, the patient was finally referred to our Cardioncology Unit for the medical assessment. The echocardiographic examination revealed a global and severe left ventricular dysfunction (FE 40%) with significant reduction in left ventricular global longitudinal strain (GLS −10%). For these reasons, we referred the patient to coronary angiography.

Conclusions
This case report wants to underline how important a dedicated cardiological follow-up is in patients undergoing chemotherapy drugs, especially if used at high doses and for many cycles.
12 Sex-related differential susceptibility to ponatinib-induced cardiotoxicity and its relationship to modulation of notch signalling in a muine model
Authors: Madonna Rosalinda , Pieragostino Damiana , Cufaro Maria Concetta , Del Boccio Piero , Pucci Angela , Mattii Letizia , Doria Vanessa , Dessalvi Christian Cadeddu , Zucchi Riccardo , Mercuro Giuseppe , De Caterina Raffaele 
Published: December 2021

Abstract

Aims
Ponatinib (PON), a tyrosine kinase inhibitor approved in chronic myeloid leukaemia, has proven cardiovascular toxicity. Although sex is a risk factor for PON-induced cardiotoxicity in humans, little is known about its mechanisms, in general, and sex-related mechanisms in particular. To determine the mechanisms of sex-related PON-induced cardiotoxicity and identify potential rescue strategies in a murine model.

Methods
Twenty-four-month-old male and female C57B5 mice were treated with 3 mg/kg/day of PON or vehicle via oral gavage for 28 days, with/without siRNA-Notch1 or siRNA-scrambled via tail vein every 3 days.

Results
PON + scrambled siRNA-treated male mice had a higher number of TUNEL-positive cells, a higher percentage of senescence-associated β-galactosidase positive senescent cardiac areas, as well as a lower reactivity degree for the survival marker Bmi1 than female counterparts. Proteomics analysis of cardiac tissue showed upstream activation of nitric oxide synthase (NOS) type 2, downstream activation of cell death and production of reactive oxygen species in PON + scrambled siRNA- compared to vehicle or PON + Notch1 siRNA-treated male mice. Upstream analysis showed beta-estradiol activation, while downstream analysis showed activation of cell survival and inhibition of cell death in PON + scrambled siRNA compared to vehicle-treated female mice. PON + scrambled siRNA-treated mice also showed a down-regulation of cardiac actin, which was more marked in male; as well as vessel density, which was more marked in female mice. Female hearts showed a greater extent of cardiac fibrosis than male counterparts at baseline, with no significant changes after PON treatment. In contrast, PON + scrambled siRNA-treated mice had less fibrosis than vehicle or PON + Notch1-siRNA-treated mice. Left ventricular systolic dysfunction shown in PON + scrambled siRNA-treated male mice and—to a lesser extent—by female mice was similarly reversed in both PON + Notch1-siRNA-treated male and female mice (Table 1).

Conclusions
We found a sex-related differential susceptibility and Notch1 modulation in PON-induced cardiotoxicity. This can improve our understanding of sex-related differences and help identify biomarkers in PON cardiotoxicity.
54 Sacubitril–valsartan (LCZ 696) improves longitudinal strain and ejection fraction in preclinical models treated with doxorubicin through NLRP3, MyD88, and pro-fibrotic chemokines
Authors: Quagliariello Vincenzo , Buccolo Simona , Iovine Martina , Maurea Fabrizio , Rea Domenica , Barbieri Antonio , Maurea Nicola 
Published: December 2021

Abstract

Aims
Doxorubicin-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in breast cancer patients. Sacubitril–valsartan (LCZ 696) is a combination drug, made up of neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan, used for the treatment of heart failure in patients with a reduced ejection fraction. We hypothesized that LCZ 696, administered during doxorubicin, could improve cardiac function and cardiac inflammation in preclinical models.

Methods
Human Foetal cardiomyocytes (HFC cell line) were exposed to subclinical concentration of doxorubicin (200 nM) alone or in combination with LCZ-696 (100 mM) for 72 h. After the incubation period, we performed the following tests: cell viability, apoptosis and necrosis; expression of malondialdehyde and 4-hydroxynonenal and concentration of intracellular Ca2+. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of TLR4/MyD88; mTORC1 Fox01/3a; NF-κB). C57Bl/6 mice were untreated (Sham, n = 6) or treated for 10 days with doxorubicin i.p. at 2.17 mg/kg (DOXO, n = 6), LCZ-696 at 60 mg/kg (LCZ, n = 6) or doxorubicin combined to LCZ-696 (DOXO-LCZ, n = 6). Ejection fraction, radial and longitudinal strain were analysed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3 inflammasome, Myd88, NF-kB, and 13 chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified.

Results
LCZ-696 exerts cardioprotective effects, enhancing cell viability of 48–54.6% compared to only doxorubicin-treated cells (P &lt; 0.001 for all); LCZ 696 decreased NLRP3, MyD88 and NF-kB expression in cardiac cells. In preclinical study, LCZ 696 improved significantly the EF and prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin. A reduced expression of NLRP3, MyD88 and NF-kB in cardiac tissues was seen in DOXO-LCZ group compared to DOXO mice (P &lt; 0.001). Cardiac expression of IL-1β, IL-6, TNF-α, G-CSF and GM-CSF were significantly reduced after treatment with LCZ-696 indicating anti-inflammatory properties.

Conclusions
LCZ-696 exerts direct beneficial effects in cardiomyocytes exposed to doxorubicin. In preclinical models, LCZ-696 reduced inflammation and cytokine expression involved in doxorubicin-mediated cardiotoxicity.