bluuebunny/crossref_metadata_2025_split huggingface dataset:
764 CARDIONEUROABLATION OF VAGALLY MEDIATED BRADYARRHYTHMIA: A SINGLE-CENTER EXPERIENCE
Authors: Valeriano Chiara , Fabbricatore Davide , Buytaert Dimitri , De Potter Tom 
Published: December 2022

Abstract

Background
Cardioneuroablation (CNA) is a novel catheter-ablation technique for the treatment of vagally-mediated bradyarrhythmia including vaso-vagal syncope (VVS), functional atrioventricular block (AVB) and sinus node dysfunction (SND). CNA aims to blunt the cardioinhibitory reflex by eliminating postganglionic parasympathetic neurons in the atrial wall and ganglionated plexi (GPs). Early-phase studies have shown promising results, but clinical evidence remains limited.

Purpose
We present our single-center experience with CNA in the setting of VVS, symptomatic functional AVB, and SND.

Methods
Baseline and procedural characteristics, procedure-related complications, and clinical outcomes were collected in patients who underwent CNA from December 2018 to July 2022. The procedural workflow included an electroanatomic mapping-guided ablation strategy, which combines the bi-atrial 3D mapping with endocardial atrial bipolar electrograms (EGM), specifically targeting high-amplitude fractionated EGM.

Results
A total of 14 CNA procedures were performed in our center. Ablation indication was mainly VVS (57%), followed by AVB (29%) and SND (14%). Syncope was the most common symptom in our cohort (71%, burden of 7 per person-lifetime). Patients were young (43±16 years) and without structural heart disease (LVEF 58±4 ml, LAD 31±7 mm). Procedures were performed under general anesthesia, mean procedure time was 102±42 min, with minimal fluoroscopy dose (2.7±1.8 Gy/cm2). We observed 1 instance of post-ablation pericarditis and 2 sinus tachycardia which required medical treatment; no major adverse events occurred. Heart rate increased after ablation in all the patients, with a mean RR interval shortening of 28% and no further increase after atropine administration. Two patients had a recurrence at a median follow-up of 251 days (IQR: 118-536), both cases were syncopal events without documentation at loop-recorder of sinus bradycardia or atrial bradyarrhythmia.

Conclusions
CNA may be an alternative to pacemaker implantation in young, highly symptomatic patients, refractory to conventional therapies and without structural heart disease. Ablation is reasonably safe in experts’ hands, especially if compared with the long-life risk of device-related complications. Further large-scale randomized studies are needed to support these findings.
205 SGLT-2 INHIBITOR DAPAGLIFLOZIN REDUCES ANTHRACYCLINE-MEDIATED CARDIOMYOPATHY IN PRECLINICAL MODELS THROUGH REDUCTION OF MYOCARDIAL NF-KB, MYD-88 AND NLRP3 EXPRESSION: A BIOCHEMICAL AND HISTOLOGICAL STUDY
Authors: Quagliariello Vincenzo , Buccolo Simona , Caronna Antonietta , Maurea Carlo , Paccone Andrea , Saviano Claudia , Bonelli Annamaria , Conforti Gabriele , Maurea Nicola 
Published: December 2022

Abstract

Background
Doxorubicin-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in breast cancer patients. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently been shown to be of therapeutic value in patients with type 2 diabetes, chronic kidney disease, and heart failure with reduced ejection fraction (HFrEF), conditions that commonly coexist and are interrelated pathophysiologically.

Purpose
We hypothesized that Dapagliflozin (an SGLT2i), administered during doxorubicin, could improve cardiac function in preclinical models

Methods
Female 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), DAPA at 12 mg/kg (DAPA, n=6) or doxorubicin combined to DAPA (DOXO-DAPA, n=6). Ejection fraction, radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3 inflammasome, Myd88, DAMPs (galectine 3 and calgranulinS100), pAMPK, 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 through ELISA and western blot methods.

Results
DAPA 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, DAMPs and NF-kB in cardiac tissues was seen in DOXO-DAPA 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 DAPA indicating anti-inflammatory properties. Expression of pAMPK was strongly enhanced in DAPA-DOXO compared to DOXO group. Levels of Calgranulin S100 and galectine-3 were strongly enhanced in DOXO group; on the other hand their expression were reduced by 47.7 and 52.3% in DAPA-DOXO group vs DOXO (p&lt;0.005). Hystology evaluation indicate reduction NF-kB expression in myocardial and renal tissue in DOXO-DAPA vs DOXO.

Conclusion
In this preclinical study, DAPA is able to improve cardiac function and reduce biomarkers involved in heart failure and fibrosis. The overall picture of the study pushes the use of DAPA in prevention of cardiomyopathies induced by anthracyclines in cancer patients.
206 LOW DOSES OF ADVANCED GLYCATION END PRODUCTS AND FRUCTOSILATION PRODUCTS PROMOTES PREMATURE CELL DEATH OF HUMAN CARDIAC CELLS AND INCREASES DRUG RESISTANCE OF HUMAN BREAST CANCER CELLS EXPOSED TO DOXORUBICIN THROUGH NLRP-3 AND MYD-88
Authors: Quagliariello Vincenzo , Maurea Fabrizio , Buccolo Simona , Caronna Antonietta , Paccone Andrea , Bonelli Annamaria , Conforti Gabriele , Saviano Claudia , D´aiuto Giuseppe , Maurea Nicola 
Published: December 2022

Abstract

Introduction
Advanced glycosylation end-products (AGEs) are non-enzyme, protein glycosylation products caused by glucose-induced metabolic disorder, and play an important role in aging, cancer, metabolic syndrome and cardiovascular diseases.

Purpose
We aimed to assess whether AGEs and fructosilation products, such as methylglyoxal (MG) and N-carboxymethyllysine (N-CML) could increase susceptibility to cell damages induced by doxorubicin

Methods
Human cardiomyocytes were pre-exposed for 24h with low doses (50 mmol/L) of methylglyoxal (MG) or N-carboxymethyllysine (N-CML). After, cells were exposed to subclinical concentration of doxorubicin (at 100 and 200 nM) for 48 and 72h. 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). Expression of p53 was also performed through western blot method

Results
Pre-exposure to methylglyoxal (MG) but especially to N-carboxymethyllysine (N-CML) increase cell mortality to doxorubicin of 48-53% compared to control. Pre-exposure to N-CML promotes premature death of cardiomyocytes to doxorubicin through NLRP3-driven pathways. Notably, MG and N-CML increased significantly the cardiotoxicity through NLRP3 inflammasome, Myd88 myddosome and cytochrome C-mediated apoptosis. Pre-exposure to N-CML and MG increase the secretion of interleukin-6 that increase cell apoptosis through a paracrine and autocrine mechanism. Induction of IL-6 reduces the expression of p53 resulting in the induction of the apoptotic process.

Conclusion
These observations suggest that AGEs and fructosilation producs promotes premature cardiotoxicity of human cardiac cells exposed to doxorubicin by activation of NLRP3, Myd88-related pathways and downregulation of p53.
551 RAPID RELATIVE EFFECTIVENESS OF A NOVEL NUTRACEUTICAL FOR THE MANAGEMENT OF HYPERCHOLESTEROLEMIA: A MULTICENTER PRIMARY CARE EXPERIENCE IN A LARGE POPULATION OF PATIENTS AT LOW TO MODERATE CARDIOVASCULAR RISK
Authors: Natale Francesco , Molinari Riccardo , Covino Simona , Alfieri Roberta , Altobelli Ippolita , Cimmino Giovanni 
Published: December 2022

Abstract

Backgroud
In the last few years increasing evidence have reinforced the benefits of low-density lipoprotrein (LDL-C) levels reduction on cardiovascular outcome. Different targets have been suggested based on the cardiovascular risk (CVR). A goal of LDL-C less of 115mg/dL is desiderable for patients at low to moderate CVR according the current european guidelines. However, an high percentage of patients at low to moderate CVR are far from this target. Nutraceuticals are “food supplements” that may help to achieve this goal in this population. The aim of this retrospective analysis was to evaluate the effects of dietary supplementation with a novel nutraceutical formulation on plasma lipid levels in subjects with low to moderate hypercholesterolemia who are not on treatment with conventional drug and/or with other dietary supplements.

Methods
Adult patients with hypercholesterolemia were retrospectively selected from the database of participant family practitioners. All patients had a baseline evaluation already recorded, including family and medical history, physical examination, and blood test that included total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), C-reactive protein (CRP), and transaminases (AST and ALT) and have started a dietary supplementation with nutraceuticals. After this selection, a total of 504 patients under this novel nutraceutical (given 1 tablet daily at dinner) with blood test at 30-days already performed, were identified. Similarly, 108 subjects with comparable clinical features but not treated with any supplements were also selected.

Results
At 30-day of follow-up, the use of this novel dietary supplement was associated with significant reduction of LDL-C 124 ± 16 vs. 100 ± 13 mg/dL, p-value &lt;0.001) and TC levels (210 ± 56 vs. 187 ± 60, p-value &lt; 0.0001), in absence of a significant changes of transaminase levels (AST: 30 ± 6 vs. 30 ± 6 U/L, p-value 0.198; ALT: AST: 30 ± 6 vs. 30 ± 6 U/L, p-value 0.325) and in CRP (3.9 ± 1.5 vs. 3.9 ± 1.4 mg/dL, p-value 0.889). No side effects were reported in the database along to the observation period.

Conclusion
This novel nutraceutical formulation is an effective dietary supplement in obtaining a significant and early reduction of LDL-C in patients with hypercholesterolemia at low to moderate cardiovascular risk.
792 FULL EVALUATION OF LEFT ATRIAL FUNCTION AFTER MITRACLIP IMPLANTATION
Authors: Ielapi Jessica , Malizia Biagio , Neri Giuseppe , Carbone Andrea , Serratore Serena , Costanzo Assunta Di , Messina Chiara , Polimeni Alberto , Mascaro Giuseppina , Mongiardo Annalisa , Spaccarotella Carmen , Indolfi Ciro , Aquila Iolanda 
Published: December 2022

Abstract

Objective
interventional edge-to-edge repair by MitraClip ™ is widely demonstrated to be able to reduce the degree of MR in patients with high surgical risk. The left atrial (LA) dysfunction in patients with severe MR is associated with poor prognosis and its changes after MV repair is reported in several studies. While, little is known about the full evaluation of the LA function by Two-dimensional speckle echocardiography tracking (2D STE)

Materials and methods
from March 2015 to December 2021, clinical and echocardiographic data of 67 patients with MR who underwent Mitraclip™ implantation in our division were evaluated for LA function. Strain Reservoir (S_R), Conduit Strain (S_Cd), Contractile Strain (S_Ct), LA emptying Fraction (LAEF_4CH), LAESV (Left atrial end-systolic volume), LAEDV (Left atrial end-diastolic volume) at baseline, at 1 month, at 6 months and 1 year of follow up were assessed. The variation of continuous variables was evaluated using a student T test for paired data. The categorical variables between baseline, at 1 month, at 6 months and 1 year of follow up were evaluated using the ANOVA test. The Multiple Bonferroni test comparison was conducted as a post hoc analysis P values &lt;0.05 were considered significant.

Results
the etiology of the MR was primary in 29,2% and secondary in 70,8% of the included patients. The MR degree was 3+ in 16,9% of patients and 4+ in 81,5%. When compared to baseline at 6 months and 1 year a statistically significant improvement was observed for LAEF_4CH (p 0.006 and &lt;0.001) and at 1 year for S_R (p 0.013) and S_Cd (p 0.033). When compared at 1 month the S-R improvement was observed at 6 months and 1 year (shown in Table 1). Finally, no significant changes were observed in S_Ct at different time point analyzed.

Conclusions
the MR improvement after MitraClip™ procedure allows hemodynamic changes with LA remodeling which can be detected by 2D STE through an improvement in LA function. These data emphasize the hypothesis that these echocardiographic parameters represent an advanced method to evaluate the response to device implantation.
180 LONG TERM FOLLOW UP OF A NON-PROGRESSIVE LEFT MAIN CORONARY ARTERY FISTULA TO RIGHT ATRIUM
Authors: Pezzato Andrea , Fabris Enrico , Korcova Renata , Belgrano Manuel , Sinagra Gianfranco 
Published: December 2022

Abstract
A 63 years old man, with multiple cardiovascular risk factor, presented at the emergency department with a transient ischemic attack during an hypertensive crisis. Electrocardiogram revealed a sinus rhythm and no sign of ischemia. No critical stenosis were detected at ultrasonography of the supra-aortic trunks. Brain CT showed an arachnoid cyst in right posterior cerebellar site. Transthoracic echocardiographic showed normal wall motion with a left ventricular ejection fraction of 66%. The transesophageal echocardiography, performed for searching possible emboligenic heart disease, revealed a fistulous aneurysmal formation arising from the left main coronary artery. Angio-CT confirmed a CAF between distal left main coronary artery and right atrium, with a retro-aortic serpiginous course and an ectasic vascular structure (above 8.35 mm), this pathological vessel also had an aneurismatic formation of maximum diameter of 1 cm. CT scan detected also a 50% soft eccentric plaque in mid circumflex coronary artery and a less than 50% soft eccentric plaque in the right coronary artery.
An elective hospitalization was performed in order to better assess the CAF. Coronary angiography revealed no significant coronary atherosclerotic disease and confirmed the CAF with its convoluted course. No left to right shunt was found either in cardiac magnetic resonance (Qp/Qs close to 1) or in right heart catheterization. Maximal stress test with cycloergometer was negative for clinical and electrocardiographic inducible ischemia (120W).
CAF is a rare vascular abnormality, occurring in only 0.002% of the general population. The majority of CAFs have a congenital origin, but occasionally they may be acquired after cardiac surgery or repeated myocardial biopsies in cardiac transplantation. The CAFs may increase in size over time, although this does not occur invariably, and complications include: myocardial ischemia (due to myocardial ‘steal’), thrombosis and embolism, heart failure, atrial fibrillation, rupture, endocarditis/endarteritis, arrhythmias and also spontaneous rupture of the CAF causing hemopericardium. Current treatment options for CAF include surgery or transcatheter closure.
Considered the age of the patient, the absence of clinical symptoms and the absence of left to right shunt, a conservative strategy was chosen. The patient had strict follow up, with clinical and echocardiographic assessment every 6 months, and with annually CT scan and stress test. During these 9 years of follow up the CAF remained stable, and the patients clinically asymptomatic.
332 RIGHT VENTRICULAR STRAIN IN FABRY CARDIOMYOPATHY: PROGNOSTIC IMPLICATIONS
Authors: Meucci Maria Chiara , Lillo Rosa , Lombardo Antonella , Lanza Gaetano A , Parisi Valentina , Grandinetti Maria , Massetti Massimo , Marsan Nina Ajmone , Crea Filippo , Graziani Francesca 
Published: December 2022

Abstract
Left ventricular (LV) hypertrophy is the main feature of Fabry cardiomyopathy (FC), but the right ventricle (RV) is also frequently affected. Previous studies failed to demonstrate an independent association between RV hypertrophy or conventional parameters of RV function and the occurrence of adverse outcomes in patients with FC. Nevertheless, if RV free wall strain (RV-FWS), assessed by 2D speckle tracking analysis, may provide a better prognostication is currently unexplored.
We retrospectively evaluated the association between RV-FWS and the occurrence of cardiovascular events in a cohort of 28 patients with FC. The study endpoint comprises the occurrence of cardiovascular mortality, severe heart failure symptoms, new-onset atrial fibrillation, bradyarrhythmias requiring pacemaker implantation and sustained ventricular tachyarrhythmias.
The median value of RV-FWS was 21.4% (interquartile range:17.1-23.9%) and a total of 18 (64%) patients showed reduced RV-FWS (&lt;23%). During a median follow-up of 49 (IQR: 37-51) months, 17 (61%) patients met the study endpoint. A ROC-curve analysis confirmed the previously defined threshold of reduced RV-FWS (23%) as the best cut-off for predicting cardiovascular outcomes at 4 years (area under curve: 0.76; p-value=0.018), but with a lower predictive value in comparison to left-sided parameters (Panel A). Kaplan-Meier survival curves showed significantly lower event-free survival at 4 years in patients with impaired RV-FWS as compared to patients with preserved RV-FWS (log rank p=0.013) (Panel B). On univariable Cox regression analysis, RV-FWS expressed as continuous variable was significantly associated with the study endpoint (Hazard ratio [HR]: 0.85, 95% CI: 0.75-0.96, p=0.009). RV-FWS retained an independent association with outcomes after alternative adjustment for age (p=0.048) or indexed LV mass (p=0.036). Conversely, RV-FWS was not significantly associated with cardiovascular events, after correcting for LV global longitudinal strain or indexed left atrial volume (p=0.401 and p=0.208; respectively).
In Conclusion, impaired RV-FWS was not independently associated with the occurrence of cardiovascular events in FC, confirming previous observations that prognosis is mainly driven by the severity of LV cardiomyopathy.
937 INCIDENTAL DIAGNOSIS OF ANOMALOUS ORIGIN AF A CORONARY ARTERY: BETTER LATE THAN NEVER.
Authors: D´elia Roberta , Vincenza Polito Maria , D´auria Federica , Lambiase Catello , Malinconico Marisa , Ciccarelli Michele , Vecchione Carmine , Galasso Gennaro 
Published: December 2022

Abstract

Background
Anomalous origin of the left circumflex coronary artery (LCx) from the right sinus of Valsalva (RSV) is the most frequent among anomalous aortic origin of the coronary arteries (AAOCA). The estimated prevalence is low (about 0.4%) and in most cases asymptomatic. Angina, shortness of breath, myocardial infarction has been described in some patients, although diagnostic and therapeutic management is controversial, particularly in elderly patients.

Case presentation
A 76-year-old female patient was admitted to our outpatient clinic for dyspnea and chest discomfort. In clinical history hypertension, dyslipidemia and diabetes were documented. Hemodynamic parameters, clinical examination and ECG were normal.
Transthoracic echocardiography showed preserved global systolic function without abnormalities of regional kinesis and valvular diseases were excluded. Interestingly, in five chambers apical view, a binary structure in the atrioventricular groove above the mitral valve plane that seemed to cross the aorta perpendicularly (RAC sign) was detected. Furthermore, in parasternal short axis view, we visualized the origins of the left and right coronaries and a blood vessel behind the aortic root, as well as a small circle below the non-coronary aortic cusp in mitroaortic angle in the parasternal long axis view (Bleb sign) was identified. We hypothesized an anomalous origin of LCx from the RSV with a retroaortic anomalous course and this was confirmed by coronary computed tomography (coroCT), that excluded an intramural course and critical stenosis of coronary arteries. Finally, we decided to perform an exercise stress echocardiography which excluded inducible myocardial ischemia. Pharmacological therapy was optimized and clinical follow-up was unremarkable.

Conclusions
AAOCA may be incidentally diagnosed also in advanced age. Specific echocardiographic signs should suggest more advanced imaging techniques to confirm the diagnostic suspect. Non-invasive multimodality imaging is crucial, in order to exclude inducible myocardial ischemia and to avoid more invasive and harmful diagnostic tests.
1062 DIAGNOSTIC AND PROGNOSTIC VALUE OF STRESS CMR IMAGING TO EVALUATE STABLE CHEST PAIN: A TWENTY-YEAR META-ANALYSIS
Authors: Ricci Fabrizio , Khanji Mohammed Yunus , Bisaccia Giandomenico , Cipriani Alberto , Cesare Annamaria Di , Ceriello Laura , Mantini Cesare , Zimarino Marco , Fedorowski Artur , Gallina Sabina , Petersen Steffen , Bucciarelli-ducci Chiara 
Published: December 2022

Abstract

Background
Assessment of inducible ischemia with stress cardiovascular magnetic resonance (CMR) is recommended in patients with chest pain and intermediate or high pre-test probability of coronary artery disease (CAD). We aimed to provide a contemporary quantitative data synthesis on diagnostic accuracy and prognostic value of stress CMR in patients with stable chest pain syndromes.

Methods
We performed a systematic review and meta-analysis of studies published over the last twenty years on the diagnostic and prognostic value of stress CMR (PROSPERO: CRD42022299275). We measured pooled diagnostic indicators, including diagnostic odds ratio (DOR), sensitivity, specificity, area under the curve (AUC), and summary effect size indicators, including odds ratios (ORs) and cumulative annualized event rates (AERs) for all-cause death, cardiovascular death and major adverse cardiac events (MACE).

Results
We identified 33 diagnostic studies pooling 7,815 individuals (mean age, 62 years, 62% males) and 31 prognostic studies pooling 67,080 patients (mean age, 62 years; 57% males; mean follow-up 3.5 years for a total of 381,357 person-years). Stress CMR yielded a pooled DOR of 26.4 (95%CI:10.6-65.9), a sensitivity of 81% (95%CI:68-89%), a specificity of 86% (95%CI:75-93%), and an AUC of 0.84 (95%CI:0.77-0.89) for the detection of functionally obstructive CAD with fractional flow reserve as the reference test. In subgroup analysis, 3 Tesla imaging yielded higher diagnostic accuracy achieving a DOR of 33.2. Presence of stress-inducible ischemia was associated with higher all-cause mortality (OR:2.0; 95%CI:1.7-2.3), cardiovascular mortality (OR:6.4; 95%CI:4.5-9.1), and increased risk of MACE (OR:5.3; 95%CI:4.0-7.0). AERs for cardiovascular death and MACE were &lt;1% in patients without stress-inducible ischemia.

Conclusions
Stress CMR yields high diagnostic accuracy and delivers robust prognostication in patients with stable chest pain and known or suspected CAD, particularly with 3 Tesla imaging. While inducible ischemia portends excess mortality and increased risk of MACE, a negative stress CMR indicates a very low risk of future cardiovascular events, with a warranty period of at least 3.5 years.