bluuebunny/crossref_metadata_2025_split huggingface dataset:
P142 PALMITOYLETHANOLAMIDE (PEA) REDUCES INFLAMMATION IN HUMAN CARDIOMYOCYTES AND VASCULAR ENDOTHELIAL CELLS EXPOSED TO DOXORUBICIN AND ANTI–HER2 MONOCLONAL ANTIBODY THROUGH PPAR–Α AND NLRP3–RELATED PATHWAYS
Authors: Quagliariello V , Buccolo S , Iovine M , Paccone A , Maurea N 
Published: May 2022

Abstract

Introduction
Palmitoylethanolamide (PEA) is an endogenous fatty acid mediator that is synthetized from membrane phospholipids by N–acyl phosphatidylethanolamine phospholipase D. It is a new analgesic drug with anti–inflammatory effects through the induction of PPAR–related pathways.

Purpose
We aimed to assess whether palmitoylethanolamide co–incubated during doxorubicin and trastuzumab, reduces anticancer drugs–related cardiotoxicity in cellular models.

Methods
Human vascular endothelial cells and cardiomyocytes were exposed to subclinical concentration of doxorubicin (at 100 and 200 nM) combined to trastuzumab (at 100 and 200 nM) alone or in combination with a formulation composed by palmitoylethanolamide 500 nM for 48h. After the incubation period, we performed the following tests: determination of cell viability, through analysis of mitochondrial dehydrogenase activity, study of lipid peroxidation (quantifying cellular Malondialdehyde and 4–hydroxynonenal), intracellular Ca2+ homeostasis. Moreover, pro–inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of peroxisome proliferator–activated receptor–α; mTORC1 Fox01/3a; transcriptional activation of p65/NF–κB and secretion of cytokines involved in cardiotoxicity (Interleukins 1β, 8, 6).

Results
Palmitoylethanolamide co–incubated with doxorubicin exerts vasculoprotective and cardioprotective effects, enhancing cell viability of 56.3–78.7 % compared to untreated cells (p &lt; 0,001 for all). Notably, PEA reduced significantly the cardiotoxicity through peroxisome proliferator–activated receptor–α –related pathways and NLRP3 inflammasome but without the involvement of calcium homeostasis. Several cytokines and chemokines were also reduced confirming its anti–inflammatory effect.

Conclusion
The present study demonstrates that palmitoylethanolamide protects against vasculotoxicity and cardiotoxicity of doxorubicin and trastuzumab by promoting an anti–inflammatory phenotype, representing a new therapeutic approach to resolve doxorubicin–induced vasculo–cardio toxicity and inflammation.
P143 EDOXABAN EFFECT IN A BREAST CANCER PATIENT WITH LIVER ARTERIAL INFUSION CHEMOTHERAPY (LAIC) AND BOTH JUGULAR VEIN AND HEPATIC ARTERY THROMBOSIS. A UNIQUE CLINICAL CASE
Authors: Fioretti A , Leopizzi T , Mariangela P , Fazio V , Ranieri G , Luzzi G , Gadaleta C , Oliva S 
Published: May 2022

Abstract

41 y–o woman, without cardiovascular risk factors, was diagnosed with breast cancer (pT2N1aMx, G3, ER:70%, PgR:30%, HER–2/NEU:2+, Ki67:60%). Treated (2010) with adjuvant antracyclines, taxanes and hormonal therapy. Subsequently, developed (2012) bone lesions treated with radiotherapy and hepatic metastases (2016) treated with systemic infusions of bevacizumab and taxanes. Started (2017) chemoembolization (CE), due to further liver severe progression configuring a main hepatic disease. Started LIVER ARTERIAL INFUSION CHEMOTHERAPY (LAIC) with 5fluoruracil and concomitant venous systemic chemotherapy (CT) with taxanes and bevacizumab. Developed (2020) arterial catheter–related thrombosis (ACRT) recurrent after urokinase, clopidogrel and enoxaparin, in spite of thromboprohylaxis with aspirin/clopidogrel. LAIC was discontinued and CT with taxanes and trastuzumab was administrated by systemic route. Left jugular deep vein thrombosis (DVT) occured (2021), treated for 8 months with low–molecular–weight heparin (LMWH): firstly with enoxaparin 100 IU/kg twice a day and secondly, because of lack of efficacy and patient’s request for a more manageable therapy, with parnaparin 6400 IU once a day. After 8 months the patient refused any more injectable anticoagulant drugs, asking for oral root of administration. LMWH were replaced by direct oral anticoagulant (DOAC), edoxaban 30 mg/die (weight: 43 kg). After 3 months of edoxaban a duplex ultrasound showed an almost total DVT regression; neither bleedings nor dru–drug interactions with the ongoing CT were detected. Instead, the 3 months follow–up CT–scan revealed persistence of the ACRT, despite of edoxaban.

Conclusions
Thromboembolism is the second leading cause of death in malignancy. Venous thromboembolic events are prevalent compared to the arterial ones. However, in active cancer hypercoagulable burden is common to both kind of thrombosis and sometimes occur simultaneously. In this case, a young woman with advanced breast cancer treated with CE and LAIC developed both DVT and ACRT. According to inefficacy and patient’s preference, we replaced LMWH with edoxaban. Arterial thrombosis was persistent although treated with several antithrombotic agents, whereas edoxaban resulted effective in the DVT regression. The take home message of this case report is that DOACs could be a feasible, efficient and safe anticoagulant choice for venous cancer related thrombosis.
P147 RECOVERY OF CHEMOTHERAPY RELATED ACUTE HEART FAILURE BY THE COMBINED USE OF SACUBITRIL VALSARTAN AND WEARABLE CARDIOVERTER DEFIBRILLATOR. A NOVEL WINNING COMBINATION IN CARDIO–ONCOLOGY
Authors: Canale M , Coviello K , Solarino G , Del Meglio J , Simonetti F , Venturini E , Camerini A , Maurea N , Bisceglia I , Tessa C , Casolo G 
Published: May 2022

Abstract
Effective anticancer treatments have dramatically improved the outcome of cancer patients but cardiac toxicity reduces their clinical efficacy in a non–negligible percentage of patients. Sacubitril/valsartan is a new paradigm in the treatment of chronic heart failure with reduced ejection fraction due to the enhancement of natriuretic peptides’ properties when coupled with a blocking effect on the AT1 angiotensin receptors. As with other clinical conditions of heart failure with potentially reversible declines in cardiac function, the wearable cardioverter defibrillator is a valid tool for protection against sudden death until recovery occurs. We report a case series of four patients with chemotherapy–related acute cardiac failure with severely reduced cardiac function. They were successfully treated with sacubitril/valsartan while being protected from malignant arrhythmias by the use of a wearable cardioverter defibrillator until the recovery of cardiac function. Sacubitril/valsartan was confirmed to be effective in anthracycline–related cardiac toxicity and the wearable cardioverter defibrillator should be considered as a support tool even in the oncology patient.
P165 CARDIOVASCULAR RISK FACTORS AND HYPOGONADISM INFLUENCE ON CARDIAC OUTCOMES IN AN AGING POPULATION OF BETA–THALASSEMIA PATIENTS: LOOKING AT THE HEART OF THE PROBLEM
Authors: Ajassa M , Gaglioti C , Longo F , Piga A , Ferrero G , Barbero U 
Published: May 2022

Abstract

Background
β–thalassemia major (β–TM) is a hereditary genetic disease hindered by many comorbidities due to transfusion–related iron. Despite iron chelation therapy increased the life expectancy up to 50 years today, Iron–related heart disease is still a leading complication, with an expected change in cardiac disease drivers with the ageing of these patients. This study aims to evaluate the distribution and prevalence of cardiovascular risk factors in a population of thalassemia major patients, and their relationship with observed cardiovascular events and potential modifying factors.

Methods and Results
One–hundred fifty–nine β–TM patients older than 18 years of age were included in this study. Mean age was 40.9 ± 8.4 years. Low serum lipid levels with low HDL levels were noted, with 28% having diabetes mellitus and 62% with hypogonadism; Splenectomy was reported in 70%. During the observed period, 3.8% of patients had at least one episode of heart failure, 35.9% showed early signs of heart failure, 22% received a diagnosis of diastolic dysfunction, 38% had a left ventricular ejection fraction &lt;55%, and 21.4% showed supraventricular arrhythmias. Cardiovascular risk was then assessed using two algorithms (CUORE and Pooled Cohort Risk Equation – PCRE) and was generally low despite the high burden of cardiac–related events. Patients with hypogonadism (who showed lower cardiac T2* value than those without; p &lt; 0.001) showed a statistically significant correlation with the occurrence of cardiovascular events.

Discussion
The β–TM population has a relatively low mean age, but shows a particular metabolic profile associated with numerous comorbidities: an increased prevalence of diabetes mellitus, low HDL values and frequent hypogonadism, which tends to be associated with increased iron deposition in the myocardium. The cardiovascular risk estimated by specific algorithms (CUORE and PCRE) was generally low, probably due to the young age of the cohort and derivation pitfalls when applied to this specific population, but the prevalence of cardiac events was not negligible.

Conclusions
The chronic accumulation of iron in the heart and the specific metabolic profile, mainly observed in patients with hypogonadism, allows us to define β–TM as a condition with high cardiovascular risk from many points of view (iron–related myopathy, atherosclerosis and arrhythmias), which requires better stratification tools and specific follow–up program.
P169 LEFT–DOMINANT ARRHYTHMOGENIC CARDIOMYOPATHY (LDAC)
Authors: Manca F , Cocco D , Pistis L , Serra E , Corda M , Marco M , Pasqualucci D , Cossa S , Pilleri A 
Published: May 2022

Abstract
Arrhythmogenic cardiomyopathy (ACM) is characterised by myocardial structural alterations with fibro–adipose replacement/infiltration, most frequently affecting the right ventricle. Malignant arrhythmias represent the most dangerous clinical manifestation.
We describe the case of a 38–year–old man who came to the Emergency Room of our hospital due to polytrauma. Following the unexpected ECG finding of signs of necrosis in the infero–lateral area and negative T waves in the antero–lateral area, a cardiological examination was performed. The patient, a smoker, had non–contributory family and personal history of cardiovascular diseases and sudden cardiac death. However, he reported several unspecified episodes of “absence seizures”. The transthoracic echocardiogram showed mild reduction in global left ventricular systolic function (EF 45–50%) due to regional changes in motion extending beyond the territory distribution of one single coronary vessel. Holter–ECG showed a Sustained Ventricular Tachycardia (SVT) symptomatic for syncope. A coronary angiography was therefore performed, which excluded any significant coronary stenosis and a cardiac MRI revealed the presence of fibro–adipose replacement of the left ventricle and, to a lesser extent, of the right side of the interventricular septum. Medical therapy with Bisoprolol, Ramipril, Spironolactone was initiated and an ICD was implanted as secondary prevention. No endomyocardial biopsy was carried out due to the high risk of the procedure; genetic testing proved to be negative. A diagnosis of borderline arrhythmogenic cardiomyopathy was therefore made. This case is of special interest as ACM with predominant left ventricular involvement (LDAC) is a rare cardiomyopathy. Diagnosis is made difficult by the presence of phenocopies and by the fact that the diagnostic criteria in use mostly focus on the forms with predominantly right–sided involvement. In the case of suspicious ECG changes, SVT or resuscitated cardiac death with imaging compatible with cardiomyopathy, it is important to raise the diagnostic suspicion of LDAC.
P170 VALUE OF ELECTROCARDIOGRAPHIC SCREENING FOR EARLY DETECTION OF ARRHYTHMIC AND MALIGNANT HEART DISEASE IN CHILDREN
Authors: Elhyka A , Fumanelli J , Di Salvo G , Iliceto S , Leoni L 
Published: May 2022

Abstract

Background
Twelve–lead electrocardiography (ECG) is a tool that can identify cardiac conduction abnormalities that predispose to sudden cardiac death (SCD) in completely asymptomatic subjects. The rate of sudden cardiac death in childhood is estimated at 1–1.5 cases per 100,000 individuals and 10–15% of events occur during physical activity. We evaluated the importance of the electrocardiogram performed in childhood in the early diagnosis of asymptomatic electrocardiographic changes suggestive for electrical or structural heart disease potentially at risk of sudden death.

Materials and Methods
we analyzed 623 patients aged 0–16 years who were referred to the pediatric arrhythmology clinic in Padua Hospital between October 2013 and March 2020. Patients were referred to our second–level clinic after a first electrocardiographic alteration found out in ECG screening performed for sports activity. All patients were evaluated with clinical history and ECG. Then, depending on the suspected pathology, Holter ECG, ergometric test, echocardiogram, MRI were performed for adequate risk stratification.

Results
Of the 623 patients evaluated, 393 (63%) were referred by sports medicine, 179 (29%) by the hospital pediatric clinic or family pediatrician, and 51 patients (8%) were referred for familiarity. 45% of patients (280) were referred for suspected WPW; 124 patients (20%) for many BEV and suspected ARVD; 85 patients (14%) for suspected long QT, 31 patients (5%) for suspected Brugada pattern; 7 patients (1%) for suspected CPVT; 8 patients (1%) for electrocardiographic changes with suspected HCM; 1 patient (0.01%) for suspected short QT and 88 patients (14%) for other arrhythmic disorders not at risk of sudden death. The diagnosis of WPW was confirmed in 280 patients (100%), LQTS in 45 patients (52%), SQTS in 1 patient (100%), S. of Brugada in 8 patients (25%), CPVT in 5 patients (71%), HCM in 8 patients (100%) and ARVD in 6 patients (5%).

Conclusions
Our study demonstrates that electrocardiographic screening in childhood allows early diagnosis and treatment of life–threatening arrhythmic heart disease.
P183 DAPAGLIFOZIN ON LEFT VENTRICULAR DIASTOLIC FUNCTION IN PATIENTS WITH TYPE 2 DIABETIC MELLITUS AND CHRONIC HEART FAILURE
Authors: Lamaida N , De Luca E , Cutolo M , Cerciello A 
Published: May 2022

Abstract

Heart failure (HF) with reduced ejection fraction (HFrEF) remains a challenging problem due to its high mortality rate. Another novelty in HF therapy is dapagliflozin, a sodium–glucose transporter–2 inhibitor (SGLT2i) which decreased the rates of cardiac death and worsening of HF in the DAPA–HF trial, when added in other guideline recommended therapy.

Material and Methods
A prospective cohort study of 30 symptomatic HF patients with EF &lt; 35% (aged 65 ±10 years) (20 males and 10 females) was conducted. Diabetic (2TDM) patients of NYHA status II–III, previously treated with ARNI, β–blocker, and mineralocorticoid receptor antagonists (MRA) were included. Dapagliflozin 10 mg was added as an adjunct therapy for 2TDM but also as a novel therapy of HF in diabetic patients. Clinical examination and complete echocardiographic evaluation were performed at baseline and 30 days after the addition of SGLT2i to their treatment. 2D echocardiography and Doppler measurements were used for the evaluation of left ventricular function, and more specifically, peak early (E–wave) and late (A–wave) transmitral filling velocities and their ratio E/A, deceleration time of E velocity (DTE) . To classify diastolic dysfunction according to the ASE/EACVI guidelines published in 2016, transmitral E and A waves velocities, septal and lateral E’ tissue velocities, indexed left atrium volume and peak velocity of tricuspid regurgitation were collected.

Results
After 30 days of therapy with dapagliflozin, blood pressure was reduced significantly and the echocardiographic parameters of diastolic function were improved. More specifically, after 6.1±3.6 months of treatment E/A ratio decreased from 1.7 ±1.5 to 1.01±0.70 (P &lt; 0.05), the E/Ea ratio decreased from 13.5± 6.3 vs. 10.2± 5.2 (P &lt; 0.05), tricuspid regurgitation peak velocity decreased from 3.0±0.4 to 2.4± 0.5m/s (P = 0.03) and left atrial volume decreased from 53 ±29.3 to 40.3±11.5ml/m2 (P &lt; 0.05). Subsequently, both left–ventricular diastolic function and filling pressure improved significantly (P &lt; 0.05, ).

Discussion
Our data support the evidence that SGLT2i ameliorate echocardiographic indexes of diastolic function. The ratio of early diastolic transmitral flow velocity seems to correlate well with LV filling pressures, and may be use das a prognostic tool in patients with HFrEF. We have to emphasize that the diastolic function improvement may be considered an early marker of improvement and adequacy .
P189 DOAC: WHEN DRUG INTERACTIONS MAKE A DIFFERENCE
Authors: Zerillo L , Oppo I , Aveta P , Rotunno R 
Published: May 2022

Abstract

Introduction
Direct oral anticoagulants (DOACs), as substrates of cytochrome P450 and / or P–glycoprotein (P–gp), are susceptible to drug–drug interactions (DDI) by both inducers and inhibitors. Awareness of this aspect is essential when choosing a DOAC, to avoid exposing the patient to an increased risk of bleeding or cardioembolicism.

Description
We report the clinical case of a 41–year–old woman with a history of iron deficiency anemia and primary hypertrophic cardiomyopathy (HCM), who came to our emergency room for an episode of atrial fibrillation with high ventricular rate (HR 140 bpm), datable (&lt;48h) and haemodynamically well tolerated. She was therefore subjected to pharmacological cardioversion with amiodarone, which was found to be effective. Subsequently, she was subjected to interrogation of the defibrillator (ICD), of which the patient was a carrier in primary prevention, with the finding of numerous episodes of AF, lasting up to several hours, paucisymptomatic. An antiarrhythmic prophylaxis with amiodarone and anticoagulant therapy with edoxaban was therefore recommended at discharge. In the following two months, in conjunction with the menstrual cycle, the patient had access to emergency room for metrorrhagia with the need for blood transfusion due to severe anemia (Hb 6 gr / dl). The gynecological tests were negative and she was entrusted to the cardiologist for the management of the therapy. Reassessed on an outpatient basis, given the impossibility of changing antiarrhythmic drugs, as amiodarone is the only molecule recommended for rhythm control in patients with this type of cardiomyopathy, and given the possible interaction between edoxaban and amiodarone (+ 40% plasma DOAC levels ), it was decided to shift to another DOAC: rivaroxaban 20 mg (less interference). In the following twelve months the patient no longer had acute anemia phenomena, the hemoglobin values remained stable and upon interrogation of the ICD device there were no arrhythmic events.

Comment
We have described this case to underline how the possible pharmacokinetic interactions between DOACs and antiarrhythmic drugs are of fundamental importance in daily clinical practice, especially when there are non–reversible causes that increase the risk of bleeding. In this case, the therapy shift vs a DOAC with a documented lower DDI interaction was found to be conclusive.
P190 CAROTID DOPPLER ULTRASONOGRAPHIC AND DAPAGLIFOZIN IN TYPE 2 DIABETIC PATIENTS
Authors: Lamaida N , De Luca E , Cutolo M , Cerciello A 
Published: May 2022

Abstract

Background
Carotid Doppler ultrasonography (USG) is widely used to measure haemodynamic parameters, such as Intima–Media Thickness (IMT) and blood flow velocities (i.e. Peak–Systolic Velocity [PSV], End–Diastolic Velocity [EDV], and Resistive Index [RI]). Dapaglifozin (SGLT2i) have been shown to reduce the risk of cardiovascular disease in type 2 diabetes (T2DM) patients. SGLT2i is a sodium–glucose co–transporter 2 inhibitor that reduces renal glucose reabsorption, thus increasing urinary glucose excretion. This leads to sustained systolic and diastolic blood pressure reduction, through natriuresis. We hypothesized that this agent would also reduce arterial stiffness.

Aim
The purpose of this study was to evaluate cardiovascular disease risk indirectly through USG of carotid artery vascular markers in T2DM patients using dapagliflozin.

Methods and Results
40 patients presenting to our clinic between march 2019 and march 2021 and diagnosed with T2DM were included in the study. These were divided into two groups : 1) a dapagliflozin group of 20 patients and 2) 20 patients non–dapagliflozin control group. Velocity parameters were: peak–systolic velocity (PSV), end–diastolic velocity (EDV), pulsatility index (PI), resistive index (RI). Examination was performed on distal portion of CCA, and we took the mean of both CCA. The mean duration of follow–up was 2.0 years. Mean ages were 55 ± 10 years in the dapagliflozin group and 50 ± 10 in the control group. Common carotid artery, PSV, and EDV parameters were higher while RI was lower (p ˂ 0.01), in the dapagliflozin group than in the control group. Vascular resistance was lower in the group using dapagliflozin for diabetes management. In addition In the dapagliflozin group, the IMT decreased after dapagliflozin therapy (P &lt; 0.01).

Conclusions
haemodynamic parameters were better performing in the group using dapagliflozin for diabetes management. Finally SGLT2i can decrease the IMT in patients with T2DM, which is closely related to cardiovascular benefit in patients with T2DM.
P198 ACUTE CORONARY SYNDROME COMPLICATED BY LEFT VENTRICULAR THROMBOSIS AND ISCHEMIC STROKE IN YOUNG WOMAN WITH ACUTE LYMPHOBLASTIC LEUKEMIA IN CHEMOTHERAPY TREATMENT
Authors: Magnano R , D‘Alleva A , Forlani D , Di Marco M , Pezzi L , Vitulli P , Fulgenzi F , Verrengia E , Paloscia L 
Published: May 2022

Abstract
Acute lymphoblastic leukemia (ALL) is the most common cancer in children and accounts for 75% of all leukemias. In ALL, very immature leukemia cells build up in the bone marrow, destroying and replacing normal cells. Thrombotic events are a complication of acute leukemia induction therapy, particularly acute lymphoblastic leukemia (ALL) treated with L – asparaginase. We present the case of a 23–year–old girl suffering from acute lymphoblastic leukemia from pediatric age, undergoing chemotherapy treatment. In August 2021 she was admitted to ICU for acute myocarditis in shock which resolved after specific therapy. In September 2021 he came to our observation again for chest pain, fever, pulmonary thickening, but with normal echocardiography and echocardiography. The next day, the patient presented a worsening of symptoms, with the appearance of an elevated ST in the anterior to the ecg trace and apical, SIV and anterior wall akinesia with severely reduced FE on the echocardiogram. After collegial discussion also with fellow haematologists for the presence of thrombocytopenia, antithrombotic therapy was administered and an urgent coronary examination was carried out. The examination showed acute thrombotic occlusion of the middle–distal VAT. In the same session we proceeded to thrombus aspiration and implantation of medicated stents, procedure concluded in the absence of complications. The following morning the patient complained of paresthesia and weakness in the right side. On the echocardiogram, the presence of a thrombus in the apical area of about 2 cm. Skull CT was performed in urgency which showed cortical–subcortical hypodensity area in the left frontal–parietal site, referring to a recent ischemic lesion. In agreement with colleagues from Stroke Unite and hematology, heparin was infused intravenously in an attempt to dissolve the thrombus, but three episodes of VF were treated with effective DC shock during the hospital stay. On the same day, the girl was transferred intubated to resuscitation for respiratory arrest; in the following hours we witnessed the exitus. Our patient presented acute thrombosis both in the heart and in the brain, although she was being treated with antiplatelet and antithrombotic drugs and in the presence of thrombocytopenia. This case highlights the strong procoagulative role of haematological disease and of the chemotherapy indicated for it.