bluuebunny/crossref_metadata_2025_split huggingface dataset:
88 Differential cardiotoxicity of immune checkpoint inhibitors involves damps fibronectin-EDA, calgranulin, galectine-3, and associated nlrp3 inflammasome-interleukins pathway in preclinical models
Authors: Quagliariello Vincenzo , Mauro Annabella Di , Scognamiglio Giosuè , Cipullo Ciro , Passariello Margherita , Barbieri Antonio , De Lorenzo Claudia , Di Bonito Maurizio , Maurea Nicola 
Published: December 2021

Abstract

Aims
Several strategies based on immune checkpoint inhibitors (ICIs) have been developed or are under investigation for cancer therapy, opening to advantages in cancer outcomes. However, several ICIs-induced side effects emerged in these patients, especially a rare but clinically significant cardiotoxicity with high rate of mortality. We analysed the differential vasculo and cardiotoxicity of Pembrolizumab, Nivolumab and Ipilimumab in preclinical models highlighting on the molecular pathways involved.

Methods
C57 female mice were treated with Ipilimumab, Pembrolizumab or Nivolumab (15 mg/kg) through intraperitoneal injection for 10 days. Before and after treatments, analysis of fractional shortening, ejection fraction, radial and longitudinal strain was performed through 2D-echocardiography (Vevo 2100, Visual Sonics Fujfilm). Fibrosis, necrosis, hypertrophy and vascular/myocardial NF-kB expression were analysed through Immunohistochemistry (IHC). DAMPs, NLRP3, MyD88, p65/NF-kB and 12 cytokines have been analysed in murine myocardium and in cardiomyocytes co-incubated with hPBMC.

Results
In preclinical models, treatment with Nivolumab leads to increased vascular and myocardial NF-kB expression without affecting fibrosis unlike Ipilimumab which also increases cardiac collagen production. Pembrolizumab increased myocardial hypertrophy and fibrosis in cardiac tissues with a strong vascular NF-kB expression. All tested ICIs increased DAMPs, NLRP3 inflammasome-IL1β-IL18 axis and only Pembrolizumab increased significantly the MyD88 expression vs. untreated mice.

Conclusions
In preclinical models, Pembrolizumab exerts the most relevant cardiotoxicity compared to Nivolumab and Ipilimumab, increasing immune infiltration in the myocardium and vascular inflammation. All tested ICIs increased DAMPs, NLRP3/IL-1β and MyD88 expression, leading to pro-inflammatory cytokine storm in heart tissues.
504 Comparison of cardiovascular risk scores to predict anthracycline-induced cardiotoxicity in early breast cancer patients
Authors: Solfanelli Giorgio , Bianchini Giulia , Petrungaro Mattia , Reale Simone , Lanza Oreste , Ferrera Armando , Tini Giacomo , Piras Marta , Pellegrini Patrizia , Tocci Giuliano , Battistoni Allegra , Volpe Massimo 
Published: December 2021

Abstract

Aims
Cardiovascular (CV) toxicities related to chemotherapy have been reported with increasing frequency. Thus, latest cardio-oncology guidelines focused on the importance of a baseline CV risk assessment before starting a potentially cardiotoxic regimen, in order to identify individuals at greater risk of developing CV toxicities and to prevent them. Despite these recommendations, there are still no validated systems to predict cardiotoxicity risk in oncological patients. The aim of the present study was to compare the average risk assessed by conventional CV risk scores (SCORE, QRISK2, ASCVD) and two recently developed cardiotoxicity risk scores (Baseline cardiovascular risk stratification proformas, Multivariable prediction model for major adverse cardiovascular events after early stage breast cancer) in a cohort of 41 (100% female; mean age 52.9 ± 11) early breast cancer (EBC) patients treated with epirubicin and to investigate the relationship between CV and cardiotoxicity risk and the rate of CV outcome, defined as biomarkers (high sensibility Troponin I and BNP) increase during the follow-up.

Results
A baseline CV risk assessment was performed in all patients before starting chemotherapy according to prespecified scores, showing a higher mean CV risk in our cohort compared to general population. Most patients were at low risk of developing cardiotoxicity according to prespecified scores. During the follow-up (mean 221 ± 75 days), the primary outcome occurred in 9.8% (n = 4). The average CV risk scores of patients developing the primary outcome were higher than the controls according to both conventional and cardiotoxicity risk scores (Figure 1). The QRISK2 achieved the best ratio cases average score/controls average score (r = 3) and the ROC curve confirmed QRISK2 as the best CV risk score to predict the outcome in our cohort, reaching the highest sensitivity and specificity (Figure 2).

Conclusions
In a cohort of young patients affected by EBC the mean CV risk is higher than the general young female population according to traditional CV risk scores. Moreover, patients developing the primary outcome during the Follow-up were those at higher CV risk and high risk of cardio toxicity. Surprisingly the best score to predict the incidence of outcome was the QRISK2, confirming the crucial role of baseline CV risk in cancer patients.
234 Echocardiographic visualization of retroaortic anomalous coronary artery
Authors: Bruno Noemi , Ferrari Ilaria , Pelliccia Francesco , Gaudio Carlo , Monzo Luca 
Published: December 2021

Abstract
A 65-year-old female was admitted to our hospital for sudden onset of typical chest pain at rest lasting few minutes. Her medical background included systemic hypertension, type 2 diabetes, dyslipidaemia, and mild obesity. Upon arrival in the emergency room, the electrocardiogram didn’t reveal signs of acute myocardial ischaemia and serial cardiac troponin T measurements were persistently negative. A transthoracic echocardiogram (TTE) was performed, showing mild ventricular hypertrophy, no regional wall motion abnormalities, and a preserved left ventricular ejection fraction. A highly echogenic tubular structure, located slightly on the atrial side of the atrioventricular groove was noted in multiple apical views. Its tubular shape was suggestive of a vascular structure, but its location was atypical for a normal vessel; indeed its persistence in more than an echocardiographic plane excluded an artefact. According to patient’s clinical history and her high cardiovascular risk profile she was referred for coronary angiography, demonstrating no critical stenosis but an anomalous aortic origin of a coronary artery (AAOCA) from the inappropriate sinus of Valsalva: the left main coronary artery (LMCA) arose from the right coronary cusp and then took a caudal posterior loop running posterior to the aortic root. In light of these findings we could associate the tubular structure seen at TTE to the retroaortic course of LMCA, a finding recently described as retroaortic anomalous coronary (RAC) sign. Among AAOCA, the retroaortic course of the LMCA is an uncommon diagnosis in adults, and its association with a single coronary origin is extremely rare. Although it has been usually considered a benign clinical entity, it is associated with an increased risk in morbidity and mortality during valve surgery. The presence of RAC sign at TTE was demonstrated to be highly suggestive of an anomalous coronary artery (specificity 93.9%) and strongly associated with retroaortic LMCA course at computed tomography angiography. 234 Figure B
314 Automated left atrial volume measurement by two-dimensional speckle-tracking echocardiograpy. Feasibility, accuracy, and reproducibility
Authors: Florescu Diana Ruxandra , Badano Luigi Paolo , Tomaselli Michele , Torlasco Camilla , Tartea Georgica , Florescu Cristina , Volpato Valentina , Parati Gianfranco , Muraru Denisa 
Published: December 2021

Abstract

Aims
A by-product of left atrial (LA) strain analysis is the automated measurement of LA maximal volume (LAVmax), which may decrease the time of echocardiography reporting, and increase the reproducibility of the LAVmax measurement. However, the automated measurement of LAVmax by two-dimensional speckle-tracking analysis (2DSTE) has never been validated. Accordingly, we sought to: (i) assess the feasibility of automated LAVmax measurement by 2DSTE; (ii) compare the automated LAVmax by 2DSTE with conventional two-dimensional (2DE) biplane and three-dimensional echocardiography (3DE) measurements; and (iii) evaluate the accuracy and reproducibility of the three echocardiography techniques.

Methods and results
LAVmax (34–197 ml) were obtained from 198/210 (feasibility 94%) consecutive patients with various cardiac diseases (median age 67 years, 126 men) by 2DSTE, 2DE, and 3DE. 2DE and 2DSTE measurements resulted in similar LAVmax values (bias = 1.5 ml, limits of agreement, LOA ± 7.5 ml), and slightly underestimated 3DE LAVmax (biases = −5 ml, LOA ± 17 ml, and −6 ml, LOA ± 16 ml, respectively). LAVmax by 2DSTE and 2DE were strongly correlated to those obtained by cardiac magnetic resonance (CMR) (r = 0.946, and r = 0.935, respectively; P &lt; 0.001). However, LAVmax obtained by 2DSTE (bias = −9.5 ml, LOA ± 16 ml) and 2DE (bias = −8 ml, LOA ± 17 ml) were significantly smaller than those measured by CMR. Conversely, 3DE LAVmax were similar to CMR (bias = −2 ml, LOA ± 10 ml). Excellent intra- and inter-observer intraclass correlations were found for 3DE (0.995 and 0.995), 2DE (0.990 and 0.988), and 2DSTE (0.990 and 0.989).

Conclusions
Automated LAVmax measurement by 2DSTE is highly feasible, highly reproducible, and provided similar values to conventional 2DE calculations in consecutive patients with a wide range of LAVmax.
310 Ruptured sinus of Valsalva aneurysm as a rare cause of sisto-diastolic murmur: role of multimodality imaging in diagnosis and surgical planning
Authors: De Luca Antonio , Fiocco Alessandro , Restivo Luca , Poletti Angela , Faganello Giorgio , Bussani Rossana , Sinagra Gianfranco 
Published: December 2021

Abstract

A 27-year-old man had an incidental finding of sisto-diastolic murmur during a screening medical evaluation. Transthoracic and subsequent transesophageal echocardiography revealed a saccular enlargement of non-coronary (NC) sinus of Valsalva. The aneurysm extended into the right atrium (RA) and presented a large wall discontinuity, with continuous sisto-diastolic flow from the aorta to the right atrium. Computed tomography confirmed the findings and excluded other associated abnormalities. The patient underwent urgent surgical intervention. Intraoperatively, findings reported a floppy and cribrose saccular aneurysm sprouting from the NC sinus inside the RA. The correction turned out to be very challenging due to the close connection between the aneurysmal wall and the tricuspid valve (TV) and aortic valve (AV) annuli. The aortic NC sinus was excised and replaced with a Dacron patch. Damaging of the TV septal leaflet required repair through a consolidating suture involving the septal leaflet of TV and the corresponding annular insertion. AV replacement was also needed due to damage of the AV NC cusp. No complications occurred during the postoperative stay. Histopathology revealed severe atrophy of muscular and elastic fibres of the aortic wall, elastic fiber fragmentation, replacement fibrosis and extensive deposition of mucopolysaccharides.

Sinus of Valsalva aneurysm (SoVA) is a rare condition characterized by an enlargement of the aortic root between the aortic valve and the sinotubular junction. SoVA can be either congenital, as a consequence of weakness of the elastic lamina, or acquired, due to infective, degenerative, or traumatic conditions. A prevalence of 0.09% was described in autopsy series and males are more frequently affected. Acute rupture of SoVA requires emergent surgery because of acute life-threatening haemodynamic instability. Congenital and chronic ruptured SoVA could be asymptomatic. Nevertheless, such incidental finding requires urgent surgical correction due to the possibility of unexpected further rupture, generating massive left-right shunt. The close relationship with nearby anatomical structures is a major issue which should be taken into account. In this perspective multimodality imaging is of paramount importance, allowing for a fine surgical planning and avoidance of complications.
122 Exercise stress echocardiography in paediatric and adolescent patients: what is the role?
Authors: Avesani Martina , Calvo Giacomo , Sabatino Jolanda , Sirico Domenico , Castaldi Biagio , Reffo Elena , Cerutti Alessia , Biffanti Roberta , Borrelli Nunzia , Piccinelli Enrico , Fraisse Alain , Padalino Massimo , Vida Vladimiro , Di Salvo Giovanni 
Published: December 2021

Abstract

Aims
To describe the current application of exercise stress echocardiography (ESE) in our Paediatric Cardiology Departments.

Methods and results
Baseline and under stress symptoms, vital parameters, ECG, and echocardiograms from patients who underwent ESE in our centres, were retrospectively analysed and compared, as well as clinical management plans formulated based on ESEs results. Forty-five patients from Centre 1 (median age 16 years), including 87% of patients with congenital heart diseases (CHDs), and 20 patients from Centre 2 (median age 11 years), mainly tested to rule out myocardial ischemia, were included. Among patients from Centre 1, 28 had previously been treated surgically, 6 percutaneously, and 11 were under follow-up. Indications for ESE/patients’ native diagnosis are illustrated in the picture. Centre 1: Exercise was maximal in 17 patients, with 2 of them having symptoms at the peak of exercise. It was stopped beforehand in 28 patients because of dyspnoea (3) and muscle fatigue (25). No arrhythmia was detected. ESE was considered as positive in 14 patients; after that, 3 patients underwent percutaneous interventions, 2 underwent cardiac surgery, 3 received indication for cardiac catheterization, 4 for advanced cardiac imaging, and 2 for exercise restriction and medical therapy. Centre 2: 15 patients (75%) completed the exercise, and none of them developed symptoms. In the remaining 25%, exercise was stopped because of muscle exhaustion. No arrhythmia was detected, and all the ESEs were negative. Comparing the cohorts, no differences in terms of ejection fraction were noticed at rest and under stress. Patients in cohort 1 were older (P = 0.002), they achieved lower average maximal heart rate (P = 0.0001), performed less lasting exercise (P = 0.05), and ESE was maximal less frequently (P = 0.005). Lastly, they had significant changes in clinical decisions (P = 0.004).

Conclusions
In paediatric cardiology, particularly in children with CHDs, ESE is a promising technique and could influence significantly clinical management plans.
45 Experience of 5 years of balloon pulmonary angioplasty in a single centre: safety and short-term results
Authors: Guarino Daniele , Palazzini Massimiliano , Saia Francesco , Dardi Fabio , Taglieri Nevio , De Lorenzis Alessandro , Ballerini Alberto , Rotunno Mariangela , Magnani Ilenia , Donato Federico , Bertozzi Riccardo , Marrozzini Cinzia , Manes Alessandra , Galiè Nazzareno 
Published: December 2021

Abstract

Aims
Balloon pulmonary angioplasty (BPA) has recently been developed as a treatment strategy for chronic thromboembolic pulmonary hypertension (CTEPH) but efficacy and technical safety have to be established. We examine the effects of BPA on patients with inoperable disease or residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA).

Methods and results
From 2015 to 2020 we enrolled symptomatic inoperable CTEPH patients and patients with residual PH after PEA. At baseline and 3 months after last BPA session patients underwent clinical evaluation, 6-min walking distance (6MWD), and right heart catheterization. Friedman test with Bonferroni post-hoc pairwise analysis was used. Fifty patients [male 42%, median age 68 (51–74) years, 42 inoperable, and 8 with residual PH after PEA] were treated for a total of 156 sessions (median 2 sessions/patient); during each session we treated 2.3 (2.2–2.7) vessels. Results are shown in the Table. Forty-nine patients were treated with medical therapy before BPA (19 with combination therapy). Five pulmonary artery dissection and two haemoptysis with clinical impairment were documented during the procedures; 37 patients had lung injury (radiographic opacity with/without haemoptysis and/or hypoxaemia), none had renal dysfunction, 7 patients had access site complications. Seven patients died during follow-up (none within 30 days from the procedure) because of sepsis (1), heart failure (1), cancer (2), arrhythmic storm (2), and sudden death in patients with severe coronary atherosclerosis (1).

Conclusions
BPA is a safe and effective treatment able to improve symptoms and haemodynamic profile. 45 Table 16MWD, six minute walking distanceCI, cardiac index; mPAP, mean pulmonary arterial pressure; PAC, pulmonary arterial compliance; PVR, pulmonary vascular resistance; RAP, right atrial pressure; SvO2, mixed venous oxygen saturation; WHO-FC, World Health Organization functional class.
53 Exercise oxygen kinetic in hypertrophic cardiomyopathy: results from a multicentre cardiopulmonary exercise testing study
Authors: Mapelli Massimo , Romani Simona , Magrì Damiano , Merlo Marco , Cittar Marco , Masé Marco , Muratori Manuela , Gallo Giovanna , Sclafani Matteo , Carriere Cosimo , Zaffalon Denise , Salvioni Elisabetta , Mattavelli Irene , Vignati Carlo , De Martino Fabiana , Rovai Sara , Autore Camillo , Sinagra Gianfranco , Agostoni Piergiuseppe 
Published: December 2021

Abstract

Aims
Reduced cardiac output (CO) has been considered crucial in symptoms’ genesis in hypertrophic cardiomyopathy (HCM). We evaluated the cardiopulmonary exercise testing (CPET) response in HCM focusing on parameters strongly associated with stroke volume (SV) and cardiac output (CO), such as oxygen uptake (VO2) and O2-pulse, considering both their absolute values and temporal behaviour during physical exercise.

Methods and results
We enrolled 312 non-end stage HCM patients, divided according to left ventricle outflow tract obstruction (LVOTO) at rest or during Valsalva manoeuver (72% with LVOTO &lt; 30; 10% between 30 and 49; and 18% ≥50 mmHg). Peak VO2 (percent of predicted), O2-pulse, and ventilation to carbon dioxide production (VE/VCO2) slope did not change across LVOTO groups. Ninety-six (31%) HCM patients presented an abnormal O2-pulse temporal behaviour, irrespective of LVOTO values. These patients showed lower peak systolic pressure, workload (106 ± 45 vs. 130 ± 49 W), VO2 (74 ± 17% vs. 80 ± 20%) and O2-pulse (12 [9–14] vs. 14 [11–17]ml/beat), with higher VE/VCO2 slope (28 [25–31] vs. 27 [24–31]) (P &lt; 0.005 for all). Only two patients had an abnormal VO2/work slope.

Conclusions
None of CPET parameters, either as absolute values or dynamic relationships, were associated with LVOTO. Differently, an abnormal O2-pulse exercise behaviour, which is strongly related to inadequate SV during exercise, correlates with reduced functional capacity (peak and anaerobic threshold VO2 and workload) and increased VE/VCO2 slope, helping identifying more advanced disease irrespectively of LVOTO. Adding O2-pulse kinetics evaluation to standard CPET could lead to a potential incremental benefit in terms of HCM prognostic stratification and, then, therapeutic management.
732 TEE role in patients selection for transcatheter edge to edge tricuspid repair
Authors: Filippis Aurelio De , Nobile Edoardo , Paolucci Luca , Vitez Luka , Bono Maria Caterina , Carpenito Myriam , Cammalleri Valeria , Mega Simona , Nusca Annunziata , Grigioni Francesco , Ussia Gian Paolo 
Published: December 2021

Abstract

Aims
The natural history of tricuspid valve (TV) regurgitation is characterized by dismal prognosis and high in-hospital mortality when treated with isolated TV surgery. Although the anatomy and the imaging of the TV are very challenging, the edge-to-edge repair with the TriClip (Abbott Vascular, Santa Clara, CA) showed promising results. We report preliminary results of our experience with the TriClip System in a cohort of ‘real life’ patients with functional tricuspid regurgitation (TR).

Methods and results
From January to September 2021, 30 consecutive patients with severe TR has been screened, 8 underwent transcatheter TriClip repair. The anatomical feasibility was established according to a complete transesophageal echocardiogram (TEE) and a dedicated CT scan for the right cardiac chambers. All the echocardiographic projections focused on right ventricle were used during the procedure, with the aim of optimizing the visualization of the catheters and device with respect to the anatomical structures of the tricuspid valve complex. The procedure was conducted under general anesthesia, guided by TEE and fluoroscopy. In-hospital and 30-day clinical and echocardiographic outcomes were recorded. The annulus septo-lateral diameter was enlarged in all cases, and functional TR was present in all patients. In two patients, the pacemaker lead interfered with leaflets coaptation. TR jet was predominantly central. The implant and procedural success were achieved in all cases, implanting one device in five patients and two in three patients. The final TR grade was 2+ in four patients and and 1+ in the others. All patients were extubated in the catheterization laboratory. There were no procedural or in-hospital adverse events. At 30-day follow-up, we observed significant improvement in clinical and echocardiographic outcomes.

Conclusions
In our experience, 26% of screened patients were selected for the procedure. Favourable anatomical findings for the TV edge-to-edge repair were the following: moderate leaflet tethering (coaptation depth &lt;10 mm); large annulus but with small coaptation gap (&lt;7 mm); antero-septal or postero-septal jet location; commissural jet; small right ventricular dimensions; pacemaker lead with no leaflet tethering. The best transcatheter approach consists of obliterating the antero-septal coaptation rim for a more favourable angle between the inferior vena cava and valvular plane. High-quality TEE imaging during the procedure is required for obtaining procedural success. Patient selection and tricuspid valve anatomy characterization with TEE and cardiac CT scan is critical for procedural success and clinical improvements.