bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial Heterogeneity of Immune Drivers Coordinates the Organisation of Antitumor Immunity in Pancreatic Cancer, Affecting Patient Outcome
Authors: Wenning A S , Aeschbacher P , Gloor B , Karamitopoulou E , Perren A , Marinoni I
Published: May 2024

Background

Pancreatic ductal adenocarcinoma (PDAC) is considered low immunogenic with “cold” tumor microenvironment (TME) and is mostly unresponsive to immune checkpoint blockade therapies.

Aims

We aim to decipher the impact of intratumoral heterogeneity of immune determinants on antitumor response.

Methods

130PDAC specimens were classified according to overall survival in long-term survivors (LTSs, n=29, OS≥60 months) and short-term survivors (STSs, n=101, OS<60 months). Spatial compartment masks were defined by immunofluorescence imaging (tumor cells: Pancytokeratin+CD45-, leukocytes: CD45+Pancytokeratin-, stroma cells: PanCK-CD45-). 4regions of interest from tumor center (TC) and the invasive front (IF) were examined by transcriptomic and proteomic analysis using the Nanostring platform for immune pathway targets. Results of NGS and morphological features were integrated. 20samples underwent immunophenotypic analysis by multiplex immunofluorescence.

Results

LTSs displayed mostly homogeneous morphology with extended glandular differentiation and immunogenic TME both at TC and IF, with increasing gradient towards the IF. There was higher presence of immune checkpoint-associated and immunogenic genes and proteins at the IF as compared to the TC, including CD40, CD3, CD8, CD4, GZMB and PD-L1. In contrast, STSs were characterized by morphologic heterogeneity, including areas with reduced glandular differentiation and high tumor budding, and a mostly immunosuppressive TME with negative gradient towards the IF. Moreover, there was reduced gene expression and protein abundance at the IF as compared to the TC, including CD3, CD8, CXCL10, GZMB, IFNG, HLA-DR and CD40.

Conclusion

LTSs display a highly immunogenic TME, underscoring their effective antitumor immunity, especially at the area of IF compared with STSs. A significant intratumoral heterogeneity between TC and IF exists with regards to immune determinants in both, LTSs and STSs, which might explain the different antitumor immune responses, affecting patient outcome. The differential expression of immune drivers may help selecting patients for combination therapies to improve antitumor immunity and harness the responsiveness to immune checkpoint inhibitors in PDAC.
Decentralized Colorectal Cancer Care: Benefit or Burden in the Pandemic? – An International Comparative Study in two Health Care Systems (DCCC Study)
Authors: Wiesler B , Gass J M , Metzger J , Hartel M , Nebiker C , Zingg U , Stimpfle D , Viehl C T , Müller A , Worni M , Studer P , Eisner L , Andreou C , Rosenberg R , Galli R , Müller B P , Denhaerynck K , Hall P , Gallagher C , Lilley C , Zuber M , Paterson H M , von Strauss Und Torney M
Published: May 2024

Background

Beneficial effects of centralization could be shown. During SARS-CoV2 pandemic however, the centralization in the UK healthcare system led to cessation of screening colonoscopies and oncological resections. In the decentralized healthcare system of Switzerland, a high frequency of colonoscopies could be maintained.

Aims

The aim of this international study is to evaluate if a decentralized health care systems can prevent the threatening unmet needs of colorectal cancer patients under pandemic conditions.

Methods

This observational trial was performed in the south-east of Scotland and in the extended northwest of Switzerland with a catchment area of 1.5 Mio. inhabitants each. Patients with colorectal cancer diagnosed during January 2019 and December 2022 were included.

Results

Six thousand six hundred and eighty patients were included in this preliminary analysis (4059 in the NHS group and 2621 in the Swiss group). In Scotland the median number of diagnosed patients per quarter was 258 pre-pandemics, 218 during lockdown and 258 after lockdown (p=0.56). There was no significant alteration of the median diagnosed patients per quarter during different phases in Switzerland (165 pre-pandemic vs. 187 during lockdown vs. 162 post-lockdown, p=0.56). In Scotland the median number of all performed tumor treatments per quarter were lower during lockdown (83 pre-pandemic vs. 75 during lockdown vs. 93 post-lockdown, p<0.01). In Switzerland the median treatment numbers per quarter didn´t differ during different phases (56 pre-pandemic vs. 62 during lockdown vs. 60 post-lockdown, p=0.51). The number of patients diagnosed with a T4 tumor during pandemic was higher in Scotland than in Switzerland (28% vs. 19%, p<0.01). The 30-day mortality under pandemic condition was 7.5% (65 of 859) in Scotland compared to 3.7% (14 of 374) in Switzerland (p=0.01).

Conclusion

SARS-CoV2 pandemic led to a reduction in performed cancer treatments in Scotland. In Switzerland's decentralized healthcare system, cancer treatments were maintained during pandemic.
Overall Survival in Patients with Esophageal Cancer and Clinical Complete Response after Radio Chemotherapy: Should a Watchful Waiting Strategy be the new Standard of Care?
Authors: Gerber S , Berger M , Hemmatazad H , Candinas D , Kröll D , Haltmeier T , Borbély Y
Published: May 2024

Background

The current standard of care for curative treatment of esophageal cancer (EC) consists of neoadjuvant radio chemotherapy (RCT) followed by resection. However, an organ-sparing approach with a watchful waiting (WW) strategy and resection only in case of cancer recurrence is gaining importance in patients with clinical complete response (cCR) after RCT. Nevertheless, data on overall survival, particularly in subgroups with and without tumor recurrence, is limited.

Aims

To compare overall survival (OS) rates in patients with cCR based on initial management and at time of recurrence.

Methods

We retrospectively analyzed data from all patients with EC and cCR to RCT between 01/2014 and 12/2021. OS- and disease-free survival was calculated using Kaplan-Meier survival analysis.

Results

Of 96 patients with cCR after RCT, 45 underwent resection (47%), and 51 (53%) a WW approach. There were no significant differences in baseline patient or tumor characteristics.

In the WW group, 28 patients (55%) had cancer recurrence. Of those, 11 patients (of 28, 39%) underwent either salvage esophagectomy or endoscopic submucosal dissection in curative intent.

No significant difference in OS could be detected in patients with WW and either no recurrence or recurrence treated in curative intention (p=0.716). Further, OS was significantly longer in those patients than in patients with primary resection (p=0.031) and WW patients with recurrence and palliative treatment (p<0.001). (Fig 1).

Conclusion

In a WW concept for patients with EC and cCR after RCT, patients with cancer recurrence can achieve the same OS as patients without recurrence if treated in curative intention. Moreover, OS in both those patient groups was superior to that of patients undergoing direct resection after RCT, supporting a WW approach as at least safe and applicable in clinical practice. Further prospective data are needed to determine the value of WW as standard of care for patients with cCR following neoadjuvant RCT.
Transgastric Laparoscopic Resection of Gastric Submucosal Tumors: An Alternative Approach in Anatomically Challenging Locations?
Authors: Kröll D , Fischer J , Borbély Y , Haltmeier T , Candinas D , Aeschbacher P
Published: May 2024

Background

Surgical resection remains the recommended method in treatment for patients with Gastrointestinal stromal tumors (GIST). However, resection in anatomically challenging locations, e.g., lesser curvature of the stomach or gastroesophageal (GE) junction, might be challenging.

Aims

We report the feasibility and the safety outcomes of a case series of patients who underwent trans gastric resection of gastric GISTs.

Methods

Patients with intraluminal GIST at the fundus, GE junction, lesser curvature, or pre-pyloric region resected with transgastral resection were included between 2023 and 2024 in a single-center institution. Data on the demographics, comorbidities, lesion parameters, operative findings, complications, and histopathology were collected.

Results

A total of 8 patients (47.5 % female; mean age 60.5 years) were identified. The average tumor size was 3.2 (range 2.7–4.1) cm. The average tumor size was 4.6 cm. No intra- or postoperative complications occurred.

Conclusion

The transgastric resection technique for GIST at anatomically challenging locations was feasible and safe and presented an alternative and additional armamentarium of resection techniques.
Mobile vs Fixed Fluoroscopy System for EVAR Image Quality and Radiation Doses for Patients and Professionnals: Mobile C-Arm vs Hybrid Room for EVAR
Authors: Déglise S , Nowak M , Labarbe A , Caldas Rodrigues J , Côté E , Trunfio R , Longchamp J , Deslarzes-Dubuis C
Published: May 2024

Background

Allowing less invasive treatments, endovascular aortic repair (EVAR) has become the gold standard worldwide for the treatment of abdominal aortic aneurysms, leading to questions regarding staff and patients’ exposure to radiation. Widely performed in our center, EVAR was initially carried out on mobile C-arm (Cios-alpha, Siemens). Since 2022, EVAR was then performed in a hybrid room (Artis-Pheno, Siemens).

Aims

The aim of this study is to compare image quality and patients and professionals’ radiation exposure between both systems.

Methods

Image quality has been tested for fluoroscopy and fluorography mode on the moving system, with PMMA plates and copper disc. A Radcal ionization chamber was used to measure patient skin dose. Dosimetric and clinical parameters (e.i. Kerma, fluoroscopy time, BMI…) were recorded for 79 and 43 patients, respectively, on mobile C-arm and hybrid room. Staff exposure was measured with thermoluminescent detectors, on an anthropomorphic phantom, representative of the physician. Scattered radiation was created by irradiating PMMA plates. Different radiation protection gears have been tested comparable to daily clinical use.

Results

We showed that using the fluoroscopy mode, Cios-alpha was more irradiating for similar image quality as compared to the Artis-Pheno. Moreover, using the fluorography mode, Artis-Pheno provided a comparable dose rate but significantly better image quality.

When comparing similar patient cohorts (BMI, sex), kerma was twice higher on Artis-Pheno due to fluorography, accounting for 27% of the total dose.

In terms of staff exposure, the dose rate decreased by 51% and 99% in fluoroscopy, and 22% and 99% in fluorography when using Artis-Pheno compared to Cios-alpha (respectively, without any and with radiation protection gear).

Conclusion

Our study highlights the advantage of a fixed system (hybrid room) in term of both image quality and staff exposure compared to mobile system. However, particular attention must be paid to optimize protocols of such a machine to guarantee the best possible radiation protection for the patient.
Neuroplasticity of visual brain network induced by hypoxia
Authors: Zhang Xinjuan , Liu Yanqiu , Yuan Fengjuan , Hang Yang , Zhang Ran , Lin Jianzhong , Wang Xiaochuan , Zhang Jiaxing
Published: May 2024

The effects of hypoxia on brain function remain largely unknown. This study aimed to clarify this issue by visual-stimulated functional magnetic resonance imaging design. Twenty-three college students with a 30-d high-altitude exposure were tested before, 1 week and 3 months after returning to sea level. Brain functional magnetic resonance imaging and retinal electroretinogram were acquired. One week after returning to sea level, decreased blood oxygenation level dependent in the right lingual gyrus accompanied with increased blood oxygenation level dependent in the frontal cortex and insular cortex, and decreased amplitude of electroretinogram a-wave in right eye; moreover, the bilateral lingual gyri showed increased functional connectivity within the dorsal visual stream pathway, and the blood oxygenation level dependent signals in the right lingual gyrus showed positive correlation with right retinal electroretinogram a-wave. Three months after returning to sea level, the blood oxygenation level dependent signals recovered to normal level, while intensively increased blood oxygenation level dependent signals in a broad of brain regions and decreased retinal electroretinogram were also existed. In conclusion, hypoxic exposure has long-term effects on visual cortex, and the impaired retinal electroretinogram may contribute to it. The increased functional connectivity of dorsal stream may compensate for the decreased function of retinal photoreceptor cells to maintain normal visual function.
Dual-layer cocatalysts of Co–Pi and Ni(OH)2 on BiVO4 photoanodes for efficient water oxidation
Authors: Zhang Yu , Guo Peng , Tang Yonghua , Li Hongxing , Mo Rong
Published: May 2024

Slow oxygen evolution kinetics and severe corrosion limit the further application of BiVO4 photoelectrodes in photoelectrochemical water splitting. Here, BiVO4/Co–Pi/Ni(OH)2 photoanodes were synthetized with the aim of improving their photoelectric conversion efficiency and stability. Compared with a pure BiVO4 photoanode, the BiVO4/Co–Pi/Ni(OH)2 photoanode enhanced the photocurrent from 1.1 to 4.5 mA/cm2 at 1.23 V versus the reversible hydrogen electrode. In addition, Ni(OH)2 acted as a corrosion protection layer on the surface of the photoanode, allowing the BiVO4/Co–Pi/Ni(OH)2 photoanode to exhibit excellent stability.
ULTRASOUND GUIDED STELLATE GANGLION BLOCK BEYOND ELECTRICAL STORM: EXPANDING CLINICAL INDICATIONS
Authors: Morena A , Angelini F , Gravinese C , Frea S , Gallone G , Bocchino P , Boretto P , De Lio G , Bruno F , Pidello S , Saglietto A , Ferraris F , Toscano A , Costamagna A , Trompeo A , Anselmino M , Rinaldi M , De Ferrari G , Dusi V
Published: May 2024

Background

Percutaneous stellate ganglion block (PSGB) is recommended by the latest American as well as European guidelines for patients with drug and eventually ventricular tachycardia (VT) ablation refractory ventricular arrhythmias (VAs) in form of electrical storm (ES). Yet, due to the strong antiarrhythmic potential, combined with the good safety profile, we’ve recently started to expand its usage to the prophylaxis of VAs in high–risk patients and the prophylaxis/treatment of atrial arrhythmias.

Methods

We hereby describe our single center experience with PSGB from 2/2021 to 12/2023.

Results

51 patients (92% male, mean age 65 ± 12 years) received a total of 69 PSGB performed with the lateral, ultrasound (US) guided technique. All procedures except for 3 in a single patient who had previously received left cardiac sympathetic denervation, were performed on the left side. Most of the patients (63%) suffered ischemic cardiomyopathy (CMP), including 6 with an over imposed acute coronary syndrome; the rest had non ischemic CMP, including 1 patient with acute myocarditis and 1 with hypertrophic CMP. Mean LVEF was 25 ± 13%. Most of the procedures (n=59, 86%) were performed due to refractory VAs, yet, 6 (8%) aimed to prevent VAs in high risk patients, mostly in the setting of recent VAs and need for levosimendan to support cardiac output, in one case due to recent stereotactic VT ablation, to prevent early VAs in the phase of acute radiation induced vascular damage. All 6 were effective in preventing clinically significant VAs. Additionally, 4 PSGBs (6%) were performed due to atrial arrhythmias with high ventricular rate despite intravenous drugs. Specifically, 3 patients had atrial fibrillation, in 2 cases with concomitant need for inotropes, and 1 patient suffered 2:1 atrial flutter. Left–sided PSGB significantly reduced ventricular rate during AF but not during the single case of 2:1 atrial flutter. Most of the procedures consisted in a single bolus anesthetic injection of lidocaine plus ropivacaine, 19 (28%) in an additional continuous infusion, mostly with ropivacaine. No major complications occurred, while minor complications were observed in 12% of PSGBs (mostly transient left arm weakness).

Conclusions

Our data suggest that US–guided PSGB usage, thanks to its easy feasibility and good safety profile, may expand, beyond ES, to not only VAs prevention in high–risk settings, but also to prophylaxis/treatment of atrial arrhythmias.
LINAC–BASED STEREOTACTIC ARRHYTHMIA RADIOABLATION (STAR) FOR PAROXYSMAL ATRIAL FIBRILLATION IN ELDERLY: A PROSPECTIVE PHASE II TRIAL
Authors: Romanazzi I , Di Monaco A , Valenti N , Troisi F , Vitulano N , Quadrini F , Grimaldi M
Published: May 2024

Background and Aims

The aim of this trial is to investigate the feasibility of radiotherapy for the treatment of paroxysmal atrial fibrillation (AF) in elderly patients.

Method

inclusion criteria were: age > 70 years, symptomatic AF, antiarrhythmic drugs failure or intolerance. All patients underwent to 4D cardiac Computed Tomography simulation. The clinical target volume was identified in the area around pulmonary veins (PV). STAR was performed with a total dose of 25 Gy (single fraction) delivered in 3 minutes.

Results

Twenty patients were enrolled and 18 underwent STAR. One patient withdrew informed consent before treatment and 1 patient was excluded due to unfavorable esophagus position. With a median follow–up (FU) of 16 months (range 12–23), no acute toxicity more than grade 3 was reported. Five patients had a grade 1 esophagitis 24 hours after STAR; eight patients had an asymptomatic grade 1 pericardial effusion, one patient had a torsade de pointes treated effectively by electrical cardioversion and subsequent cardiac ICD implantation. Most patients had a significant reduction in AF episodes. Five patients, due to arrhythmias recurrences after STAR, performed electrophysiological study documenting successful PV isolation. Finally, a significant improvement of quality of life was documented (48 ± 15 at enrollment vs 75 ± 15 at 12 months FU; p < 0.001).

Conclusion

The present phase II trial demonstrated the feasibility of STAR in paroxysmal AF elderly patients and its potential role in increasing the quality of life. Surely, more robust data are needed about safety and efficacy.
A NETWORK META–ANALYSIS COMPARING PULSED–FIELD ABLATION (PFA) AND OTHER CURRENT ABLATION THERAPIES FOR PAROXYSMAL ATRIAL FIBRILLATION
Authors: Piccolo S , Varotto L , Borio G , Paccanaro M , Rossillo A , Vittadello S , Caprioglio F , Bonanno C
Published: May 2024

Introduction

Pulsed–field ablation (PFA) has emerged as a non–thermal catheter–based treatment for paroxysmal atrial fibrillation. This study aimed to compare the efficacy of PFA with various conventional thermal ablation methods that are currently available.

Method

Randomised controlled trials were retrieved to compare atrial tachyarrhythmia recurrence among any combination of ablation modalities. A Bayesian and frequentist network meta–analysis (NMA) using risk ratio (RR) was conducted with MetaInsight v5.1.1. Treatment strategies were ranked using the surface under the cumulative ranking area (SUCRA).

Results

Across 14 studies comparing five ablation therapies (3,233 patients), Bayesian NMA–derived RRs of atrial arrhythmia recurrence compared to PFA were 0.90 (95% Credible Interval [CrI]=0.57–1.45) for cryoballoon ablation (CBA), 0.99 (95% CrI=0.61–1.55) for radiofrequency ablation (RFA), 1.07 (95% CrI=0.61–1.87) for combined CBA and RFA, and 0.81 (95% CrI=0.43–1.51) for laser–balloon ablation (LBA) (Figure 1). Similarly, the frequentist–based NMAs showed no significant benefit of all ablation therapies over PFA. The direct and indirect comparison among the various ablation techniques showed similar outcomes within the different ablation modalities evaluated in this NMA. The higher SUCRA value for LBA (80%) indicated the likelihood that the treatment is the best, followed by CBA (67%), PFA (48%), and RFA (45%) (Figure 2).

Conclusions

This NMA demonstrated that among patients with paroxysmal atrial fibrillation receiving a catheter–based therapy, PFA was non–inferior to conventional thermal ablation concerning freedom from documented atrial tachyarrhythmia during follow–up.
INITIAL EXPERIENCE IN TOTAL ENDOSCOPIC MITRAL VALVE SURGERY WITH THREE–DIMENSIONAL VIDEO–ASSISTED TECHNOLOGY
Authors: Fiorentino M , Mikus E , Vostantino A , Sangiorgi D , Tenti E , Tremoli E , Savini C
Published: May 2024

Background

Minimally invasive approach is nowadays the gold standard for mitral valve disease treatment. New technological tools are the key to improve surgical results and to reduce the biological invasiveness. We report our initial experience in total endoscopic mitral valve surgery using three–dimensional video–assisted technology (EinsteinVision® 3.0, B. Braun, Aesculap AG, Tuttlingen, Germany).

Methods

From July 2023 to December 2023, 29 patients underwent total endoscopic mitral valve surgery with three–dimensional video–assisted technology and discharged.

Results

Median (Q1–Q3) age of our population was 60 years (47–67) and 65.5% were males. Median (Q1–Q3) logistic Euroscore was 2.09 (1.5–4.4) and median (Q1–Q3) EuroSCORE II was 0.84 (0.6–1.2). The majority of patients were in NYHA class II and the 48.3% presented with pulmonary hypertension (PAPs > 30 mmHg). Median PAPs resulted 34.5 mmHg. One patient (3.4%) suffered from mitral valve endocarditis. No conversion to full sternotomy was necessary. In six patients with left coronary dominance (20.6%) we used indocyanine green fluorescence to conduct a real–time analysis of the course of the circumflex artery during surgery. No perioperative acute myocardial infarction was observed. No 30–day mortality was reported. One patient (3.4%) suffered from renal failure requiring dialysis, respiratory failure with tracheostomy and pneumonia. Post–operative atrial fibrillation was observed in 7 patients (24.1%) and 1 patient (3.4%) required Pace–maker implantation due to third degree AV block. No re–thoracotomy for bleeding was observed and 24.1% of patients required transfusions with packed blood cells. Non stroke were detected. Median (Q1–Q3) ventilation time was 5 hours (4–7). Median (Q1–Q3) intensive care unit postoperative length of stay were 2 (2–2) days and 7 (7–8) days respectively.

Conclusions

In our experience, total endoscopic mitral valve surgery with three–dimensional video–assisted technology is safe and feasible with good postoperative outcomes. Moreover, the possibility to use indocyanine green fluorescence to detect the course of the circumflex artery significantly assist surgeons in localizing and avoiding it, thus reducing the risk of perioperative myocardial infarction.
GENOTYPE–PHENOTYPE CORRELATION IN A SINGLE CENTRE COHORT OF PATIENTS AFFECTED BY HYPERTROPHIC CARDIOMYIOPATHY
Authors: Manai R , Pidello S , Dusi V , Bocchino P , Angelini F , De Lio G , Gallone G , Gobello G , Deaglio S , Marcelli G , Raineri C , Brach Del Prever G , De Ferrari G
Published: May 2024

Background

Over the last 30 years, major advances have been made in the identification of the genetic basis of Hypertrophic Cardiomyopathy (HCM) and the spectrum of sarcomeric genes has been gradually extended to non–sarcomeric genes. Multiple attempts to identify genes with an unfavorable impact on prognosis failed; data for genotype–phenotype relationships are still insufficient.

Objective

Assess the clinical presentation and genotype–phenotype correlation of patients (pts) and the prognostic impact and clinical relevance of genetic tests.

Methods

130 adults pts with HCM were enrolled from January 2019 to May 2023. The included patients underwent blood sampling for genetic investigation.

Results

34 pts were HCM phenocopies (see figure 1). Our analysis was focused on the 96 (74%) pts with HCM. 40 pts carried likely pathogenetic/pathogenetic (LP/P) variants;23 pts carried a variant of uncertain significance; 33 pts had a negative genetic test. The majority of the pts carried MYH7 gene variants, followed by variants of MYBPC3 (see figure 1). Age at diagnosis had a significant effect on the likelihood of identifying a LP/P or VUS variant (54.44±12.7 for genetic test negative, 41.09±16.9 for VUS carriers, 35.4±15.3 for LP/P carriers, p.0.001). The presence of hypertension significantly affected the likelihood of identifying a negative genetic test (p 0.002). LP/P/VUS variants were significantly more common in patients with a family history of cardiomyopathies (p 0.001). 26% of VUS carriers and 17% of LP/P carriers had advanced heart failure; only 3% of patients with negative genetic test showed advanced heart failure (p 0.04). Carriers of LP/P variants showed more asymmetric hypertrophy, while patients with a genetic test negative showed more concentric hypertrophy. The composite endpoint (hospitalization for heart failure, cardiovascular death and cardiac transplantation) occurred in 8 (24.2%) patients with negative genetics, 16 (69.5%) patients with VUS and 14 (35%) patients with LP/P variants with a statistically significant difference (p=0.03) (see table 1). On multivariable analysis, having a positive genetic test (VUS/LP/P) was found to increase the probability of having the event by 3.8 fold compared to patients with a negative genetic test having a negative variant(see table 2).

Conclusion

We demonstrated the correlation between anamnestic data, cardiac phenotype and genotype. Genetic testing has also a prognostic value.
CARDIAC CT–PERFUSION IMAGING IN MYOCARDIAL BRIDGING EVALUATION: A NOVEL WEAPON FOR NON–INVASIVE ASSESSMENT OF A SILENT KILLER
Authors: Paolini E , Fogante M , Cela F , Schicchi N , Esposto Pirani P , Perna G
Published: May 2024

Introduction

Myocardial bridging (MB) is a congenital anomaly characterized by the intramyocardial course of one or more coronary arteries that provokes endothelial dysfunction and can generate myocardial ischemia with its pathological consequences. Because of the dynamic nature of the ischemic mechanism, a high–sensitivity myocardial perfusion stress test is often needed to decide on the correct management of the patient, mainly single photon emission computed tomography (SPECT). As an alternative to SPECT, our center offers the possibility of performing a dynamic stress–rest cCT–MPI (cardiac computed tomography – myocardial perfusion imaging).

Hypothesis

To compare the feasibility of performing cCT–MPI for the functional evaluation of MBs.

Methods

All cases underwent cCT (192–slice dual–source Somatom Force CT scanner, Siemens Healthcare, Germany), cCT–MPI with administration of a standard intravenous dose of 0.4 mg of regadenoson (Rapiscan®, GE Healthcare), and SPECT with physical stress (the latter not performed in one case of a minor patient, in favor of a coronary angiography with functional tests). Image processing was performed using Siemens Syngo® software, which can provide perfusion maps of myocardial blood flow (MBF) and volume (MBV) in a planar and 17 segments Bull‘s eye view. The interpretation of the results was performed toghether by an expert radiologist and cardiologist, both on a qualitative (color map) and quantitative basis (MBF ratio).

Results

From May 2022 to September 2023, 15 cases of MB with otherwise intact coronary arteries were collected, all involving the LAD and with anatomical characteristics considered "dangerous", i.e. length >2.5 cm and depth >2 mm. The investigations carried out revealed two relevant results: the first is that, despite all the selected MBs had anatomical features of complexity, a reversible perfusion defect related to MB was detected in only 2 cases (13%), one of which was confirmed by SPECT investigation and the other by functional tests during coronary angiography; the second is the high positive and negative concordance between cCT–MPI with pharmacological stress and SPECT with physical stress.

Conclusion

Myocardial bridging is an increasing finding detected through cCT investigations, but in a minority of cases it carries hemodynamic consequences. cCT followed in the same session by cCT–MPI with regadenoson administration constitutes two stages of the same exam.
CHARACTERISTICS AND OUTCOME OF PATIENTS WITH VARIOUS TYPE OF ACUTE CORONARY SYNDROME
Authors: Aleksova A , Fluca A , Munaretto L , Chiaradia V , Barbati G , Derin A , D‘Errico S , Di Lenarda A , Hiche C , Sinagra G , Janjusevic M
Published: May 2024

Background and Aim

Acute coronary syndrome with non–critical coronary arteries comprises distinct entities with unique pathophysiological, diagnostic, therapeutic and prognostic characteristics. The aim was to compare the clinical and prognostic features of cohorts presenting NSTEMI and non–critical coronary arteries disease, i.e. MINOCA, type 2 myocardial infarction (MI), Takotsubo syndrome (TTS), with a cohort of classical type 1 MI with critical coronary arteries disease.

Methods

In this single–center observational retrospective study, 18223 patients who underwent invasive coronary angiography between 2005 and 2022 were screened. Overall, 1162 patients were included (301 MINOCA, 237 type 2 MI, 138 TTS, and 486 with type 1 MI). The primary endpoint was a composite of non–fatal acute MI, non–fatal TIA or stroke, hospitalization for HF (hHF), and death. Secondary endpoints were (1) hHF, (2) a composite event of atrial fibrillation (AF), TIA, and/or stroke, and (3) all–cause mortality.

Results

The average age was 68.2 years, with 47% being male. At admission, the TTS group was the most hypotensive and echocardiographic compromised, with lower incidence of obesity and diabetes mellitus (DM). Type 2 MI group was more prone to hypertension and had a similar incidence of DM and diastolic dysfunction compared to type 1 MI. However, compared to type 1 MI, type 2 MI patients received less frequent DAPT, nitrates, beta–blockers, and statins upon discharge. The MINOCA group received therapy similar to type 1 MI. Over a median follow–up of 62 [30–102] months, 358 patients reached the primary endpoint, 84 had hHF, 76 had AF/TIA/stroke, and 253 died. At Kaplan–Meier analysis, type 2 MI patients were more likely to reach the primary endpoint, following type 1 MI (Fig.1). TTS group had the best outcomes (p<0.01) for death (p<0.01) and HFh. (p<0.01), while type 2 MI had higher probability of developing AF/TIA/stroke (p<0.01) (Fig.2). Cox Regression analysis confirmed type 1 MI as a predictor of worse outcomes compared to other groups, after adjustment for male gender, older age, DM, anemia, reduced systolic function, high C–reactive protein, left bundle branch block, and statins on discharge (Fig.3).

Conclusions

Critical coronary disease is confirmed to have the worst prognosis. Although type 2 MI had similar clinical characteristics as type 1 MI, the former was more burdened by arrhythmic and embolic events and diverged in therapy at the time of discharge.
DONORS WITH OUT OF HOSPITAL CARDIAC ARREST (OHCA): A SINGLE–CENTER EXPERIENCE
Authors: Fischetti G , Giovannico L , Parigino D , Santeramo V , Savino L , Silva A , Di Bari N , Bottio T
Published: May 2024

Aim

Out of Hospital Cardiac Arrest (OHCA) could be an alternative to existing efforts towards increasing the available pool of organs. The objective of this work is to demonstrate how hearts derived from marginal donors with Out of Hospital Cardiac Arrest (OHCA) have a quality that is not inferior in terms of survival compared to hearts originating from standard patients.

Methods

We performed a retrospective analysis in patients who received donor heart transplants with cardiac arrest of 20 minutes or more. The average time to cardiac arrest was 21 (±8.76) minutes. From January 2022 to September 2023, 70 cardiac transplants were performed at our cardiac surgery center, of which 74.24% were men (n=52) and 25.76 % women (n=18). The two populations compared showed similar characteristics in terms of risk factors, age, urgency/emergency status, ecmo before HTx.

Results

Patients who received hearts from donors with OHCA were 12,86% (n=9). Kaplan Meier survival curve show Kaplan Meier survival curve shows comparable 30–day survival in the two groups with a non–significant statistical difference (p = 0,5). In the group considered there is no significant difference in the use of post–operative VA ECMO (Group uDCD 22% post–HTx ECMO–VA, Group Control 23% post HTx ECMO–VA, p= 0,98).

Conclusion

According to these results it is possible to appreciate how OHCA hearts do not show inferior survival compared to hearts derived from patients who died from cerebral hemorrhage or other causes. Longer–term follow–up is necessary to evaluate the survival of such recipients.
TELEMONITORING IN PATIENTS WITH CHRONIC HEART FAILURE: EXPERIENCE FROM THE TELECUORE PROJECT IN PIACENZA
Authors: Novara P , Matrone B , Di Spigno F , Tedeschi A , Sticozzi C , Lisè G , Ballerio N , Pisati M , Ferraro S , Aschieri D
Published: May 2024

Background

Starting from February 2023, the Piacenza’s Hospital has approved the use of a cardiological telemonitoring system called ‘TeleCuore’ project. This system, through the monitoring of various vital parameters which are frequently sent by patients via a dedicated platform, allows for remote assessment of the clinical status of 250 individuals with chronic heart failure (CHF).

Objectives

The objective of this study is to analyze the number and nature of alerts in the data sent by patients and the consequences on patient’s management derived from the alerts received through the telemedicine system.

Materials and Methods

250 patients with CHF identified following recent episodes of clinical instability have been equipped with a home monitoring device (Adilife system). This involves collecting the following data: body weight, temperature, blood pressure, heart and respiratory rate, oxygen saturation, and single–lead EKG. These data are daily filtered by perfusionist technicians (TFCPC) and dedicated nurses, reviewed by the Case Manager and cardiologists. In case of recognition of altered parameters, the platform generates alerts according to pre–set clinical parameters, enabling proactive and personalized interventions on patients. In the 9 months of the TeleCuore project, 494 alerts were received, with 119 (24%) judged not clinically relevant, while 375 (76%) required operator intervention. Of these, 99 were due to weight gain (26%), 40 to low blood pressure (11%), 42 to high blood pressure (11%), 33 to tachycardia episodes (9%), 30 to bradycardia (8%), 49 for technic issues with the weight scale (13%), 78 for EKG artifacts (21%), and 4 for previously unknown atrial fibrillation (1%). 25 patients (8%) were invited for ambulatory clinical evaluation, 28 (7%) were managed through teleconsultation, and the remaining majority (85%) was handled via telephone contact for therapy adjustments (60.5%). 39.4% underwent re–training on the correct device use in the first month.

Conclusions

The TeleCuore Project is a pilot cardiological telemedicine initiative. Initial data confirm the utility of this system in optimizing the follow–up of patients with CHF, allowing for instant therapeutic adjustments based on the patient’s clinical progress. Teamwork of different healthcare professionals have emerged as crucial for the proper management of alerts. Further data will be needed to assess whether TeleCuore also helps reduce hospitalizations related to CHF.
HEART FAILURE AND ITS PHENOTYPES IN THE REAL WORLD: DATA FROM THE CARDIOVASCULAR OBSERVATORY OF FRIULI–VENEZIA GIULIA
Authors: Russo G , Cittar M , Cappelletto C , Cherubini A , Bollini M , Faganello G , Grande E , Mattei L , Mazzone C , Fisicaro M , Sola G , Zeriali N , Zorzin Fantasia A , Ius A , Montesi M , Radini D , Di Lenarda A
Published: May 2024

Introduction

Heart Failure (HF) is a disease with high mortality and morbidity burden. Guidelines classify HF according the ejection fraction (EF) in three phenotypes. HF with preserved ejection fraction (HFpEF) is the most prevalent in the real world for increasing in life expectancy and the presence of many comorbidities.

Aim

Knowing and analysing the epidemiology and clinic features of HF to create the most appropriate diagnostic–therapeutic pathways. The Cardiovascular Observatory of Friuli–Venezia Giulia (CVOFVG), which allows this analysis, is a powerful tool for clinical governance.

Results

In Friuli Venezia Giulia, at 1st January 2023, 21.212 alive patients had a HF diagnosis (1.78% prevalence). Considering the different phenotypes, in the real world, from 2018 to 2023, the most prevalent patients had EF > 40% (in 2022: HFpEF 55%, HFmrEF 9% and HFimpEF 20%). In our registry patients with HFpEF are older (mean age 80±10 yrs vs 79±11 yrs in HFmrEF vs 76±11 yrs in HFrEF), mostly women (52% vs 38% in HFmrEF, vs 27% in HFrEF), with many cardiovascular (CV) diseases, such as atrial fibrillation (57% vs 53% in HFmrEF vs 49% in HFrEF) and non CV as obesity and chronic obstructive pulmonary disease. As expected, ischemic heart disease is prevalent in HFrEF in 59% vs 38% in HFpEF. In the CVOFVG, in 2022 the hospitalization rate was 1260/100000 inhabitants (262 for HF hospitalization, 188 for CV causes, 808 for non CV disease). HFrEF has a higher incidence of HF hospitalization (54.3 on 166.2/100.000 totals). Furthermore, HFpEF because of its high prevalence, has a higher rate of CV and HF hospitalization than HFrEF (77.8 vs 54.3/100.000 inhabitants for year, 929 hospitalization vs 646). The mortality in one year is higher in HFrEF and HFmrEF vs HFpEF and above all HFimpEF. Drug prescription was different from clinical trial: in 2022, 72.2% of HFrEF patients received renin angiotensin system inhibitors (RASi), 89.2% beta blockers (BB), 62.6% mineralocorticoid receptor antagonist (MRA) and 44% SGLT2–inibitors (SGLT2–I). Same prescription for RASi, BB, MRA was in HFimpEF and HFmrEF, less for HFpEF.

Conclusions

The patients’ complexity, their increasing number, the new drugs for HFpEF lead to create multidisciplinary pathways, above all for HFpEF patients who are frequently visited by General Physicians, Internal Physicians and Geriatrics, to select the most complex case where a therapeutic intervention can be efficacy.
HIGH LEVELS OF SOLUBLE–SUPRESSION OF TUMORIGENICITY(S–ST2) PREDICT RIGHT VENTRICULAR/PULMONARY ARTERY UNCOUPLING WITH TAPSE/PAPS IN PATIENTS AFFECTED BY PULMONARY HYPERTENSION
Authors: Novielli M , De Tommasi E , Camassa N , De Michele L , Mannarini A , Cipollone E , Civino F , Fratini N , Giorgio A , Tota A , Palmieri V , Di Serio F , Colonna P , D‘Agostino C
Published: May 2024

Introduction

Pulmonary hypertension (PH) is a disease with an unfavorable prognosis, characterized by increasing in pulmonary resistence and right heart failure. One of the most important prognostic factors is the adaptation of the right ventricle to increased pressure overload, witch can be evaluated through tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure (TAPSE/PAPs), a prognostic echocardiographic index of right ventricle–pulmonary artery coupling. In this setting, NT–proBNP, until now, is the only biomarker that, reflecting right ventricular function, gives prognostic information. However, NT–proBNP levels are influenced by age, body mass index, sex and comorbidities, such as anemia and renal failure. In previous studies soluble– Suppression of Tumorigenicity (s–ST2), a marker of myocardial stress, resulted a strong predictor of death in heart failure, acute coronary syndromes and pulmonary hypertension.

Aim

Our purpose is to study the possible correlation between sST2 and different echocardiographic parameters, in particular TAPSE/PAPs.

Methods

This is a prospective study conducted on 45 PH patients (75% affected by pulmonary arterial hypertension), which were followed for survival. They underwent echocardiography, right heart catheterization and venous sampling to measure s–ST2 levels.

Results

During an average 18–month follow–up, 17 patients died, 76% of whom had pulmonary arterial hypertension (PAH). sST2>78 ng/ml represents a numerical value with the highest association with mortality in our study population: at 6–12 months the patients with sST2>78 ng/ml showed statistically significant early higher mortality in comparison with sST2 <78 ng/ml patients. Patients with sST2>78ng/ml had statistically significantly higher right ventricular inflow diameter, reduced tricuspid annular planer systolic excursion, greater right atrial area, lower pulmonary artery acceleration time and lower TAPSE/PAPs, compared with patients with sST2<78 ng/ml values. We showed a statistically significant inverse correlation between sST2 and TAPSE/PAPs.

Conclusions

s–ST2, predicting right ventricular/pulmonary artery coupling through TAPSE/PAPs, represents an usefull and promising marker in noninvasive hemodynamic assessment and risk stratification of PH patients.
EFFICACY OF COLCHICINE IN ADDITION TO ANAKINRA IN PATIENTS WITH RECURRENT PERICARDITIS
Authors: Collini V , Andreis A , De Biasio M , Isola M , De Martino M , Lepre V , Siega Vignut L , Cantarini L , Merlo M , Abbate A , Lazaros G , Brucato A , Klein A , Imazio M
Published: May 2024

Aim

Anakinra, an anti IL–1 agent targeting IL–1 alfa and beta, is available for the treatment of recurrent pericarditis in cases with corticosteroid dependence and colchicine resistance after failure of conventional therapies. However, it is unclear if the combination with colchicine, a non–specific inhibitor of the inflammasome targeting the same inflammatory pathway of IL–1, could provide additional benefit to prevent further recurrences. Aim of the present observational study is to assess whether the addition of colchicine on top of anakinra could prolong the time to first recurrence and prevent recurrences better than anakinra alone.

Methods

International, all–comers, multi–center, observational cohort study analysing consecutive patients treated with anakinra for corticosteroid dependent and colchicine resistant recurrent pericarditis. The efficacy end point was recurrence rate and the time to the first recurrence.

Results

A total of 256 patients (mean age 45.0 ± 15.4 years, 65.6% females, 80.9% with idiopathic/viral etiology) were included. 64 (25.0%) were treated with anakinra as monotherapy while 192 (75.0%) with both anakinra and colchicine. After a follow up of 12 months, 56 (21.9%) patients had recurrences. Patients treated with colchicine added to anakinra had a lower incidence of recurrences (respectively 18.8% vs. 31.3%; p=0.036) and a longer event–free survival (p=0.025). In multivariable analysis, colchicine use prevented recurrences (HR 0.52, 95% CI 0.29 to 0.91; p=0.021).

Conclusions

The addition of colchicine on top of anakinra treatment could be helpful to reduce recurrences and prolong the recurrence–free survival.
CASE PRESENTATION: A COMPLEX CLINICAL SCENARIO IN A 43–YEAR–OLD MALE WITH DEVICE–RELATED COMPLICATIONS
Authors: Zarra S
Published: May 2024

A 43 yo male presented with an exposed pocket of his ICD in the right prepectoral and axillary region, along with total exposure of the lead electrodes up to the fixation sleeves.The patient, a known carrier of double–outlet right ventricle, underwent surgical correction. At the age of one, he received a dual–chamber pacemaker in the left prepectoral region due to AVB. Due to recurrent sustained ventricular tachycardias an ICD was implanted in the right prepectoral region, with removal of the left–sided pacemaker and concurrent abandonment of the ventricular pacing lead. In October 2019, he was admitted for a recurrence of pocket erosion.Device extraction was proposed but declined by the patient. Subsequently, he was referred to our institution for device removal. After heart team discussion, the patient was offered a transvenous lead extraction, with potential cardiothoracic surgical intervention if transvenous extraction proved to be challenging.An attempt was made to extract the leads using a transvenous approach. The procedure proceeded without complications, and the leads were released from adhesions up to the superior vena cava. However, there was an adhesion point at this location that was not overcome by mechanical dilation.Due to this limitation, a few days later, a cardiothoracic surgical intervention was performed to complete the lead wires‘ extraction using an invasive approach. In this context, a cardiac resynchronization device CRT–P was reimplanted in the left prepectoral region with epicardial electrodes. The patient underwent submuscular subclavian implantation of a SCID.The patient presented with a new pocket erosion of the CRT–P.Considering the high infection risk, It was therefore decided to implant a leadless device following electroanatomic mapping of the right ventricle, as there were surgical patches in the septal region. This approach aimed to identify the optimal anchoring site for the device. Subsequently, he will go extraction of the generator of the CRT–P.The decision to forgo biventricular stimulation was made, because of the elevated infectious risk.Complications associated with implantable devices pose an increasingly significant challenge in managing young patients with cardiac arrhythmias. Only through an integrated approach and proactive sharing of knowledge and expertise can we significantly improve clinical outcomes and the quality of life for this increasingly relevant population.
NAVIGATING THE UNCHARTED WATERS: MANAGING CONCURRENT CYTOMEGALOVIRUS MYOCARDITIS AND ALLOGRAFT REJECTION IN A PATIENT WITH HEART TRANSPLANTATION
Authors: Abete R , Iacovoni A , Vittori C , Candiago E , Gianatti A , Terzi A , Sebastiani R , Senni M
Published: May 2024

A 49–year–old female with hypertrophic cardiomyopathy underwent orthotopic heart transplantation. She was cytomegalovirus(CMV)–positive and received a heart from a CMV–negative donor, so prophylaptic therapy was not administered. Initial immunosuppression included cyclosporine and induction with Basiliximab in a steroid–free regimen. The first routine biopsy (EMB) showed mild focal cellular rejection (grade 1A) and C4d positivity with granular aspect. Mycophenolate mofetil (MMF) was added. The second EMB, 7 days later, showed mild diffuse cellular rejection (grade 1B) and diffuse C4d positivity. Anti–HLA donor–specific antibodies (DSA) had increased anti–B13 levels (MFI=21298) compared to pre–transplantation tests. Echocardiography showed a normal ejection fraction (LVEF) and mild concentric hypertrophy (LVH). Treatment included pulse methylprednisolone therapy (1 g/day for three days) followed by oral prednisone with a slow tapering regimen, and increased MMF. CMV count weekly monitored was negative. The next two EMBs performed one week apart from each other described a grade 1A mild focal pattern while the 5th EMB (1 month and 2 weeks post–transplant) showed a grade 1A rejection together with focal mild fibrosis and eosinophils, so we replaced cyclosporine with tacrolimus, increased MMF and prednisone. At this time, the patient had no overt clinical signs of CMV infection but a CMV–PCR of 100847 IU/mL so ganciclovir 5 mg/Kg bid was started and CMV–PCR decreased to 42308 IU/mL after 1 week. Subsequently, she developed sinus tachycardia, mildly reduced LVEF, moderate LVH and diastolic dysfunction. Troponin was elevated. A new EMB revealed interstitial edema, diffuse ischemic injury, and eosinophilic inclusions suggesting CMV myocarditis. Treatment involved down–titrating MMF and Prednisone, administering standard intravenous immunoglobulin (IVIG), and high–dose Ganciclovir (7.5 mg/Kg bid). Leukopenia subsequently led to Ganciclovir down–titration. In the next days, the patient improved, CMV cleared, and leukocyte count normalized. She was discharged on Tacrolimus, MMF, Prednisone and Valganciclovir. Subsequent tests showed no cellular or antibody–mediated rejection (AMR), no CMV inclusions, recovered cardiac function, and markedly reduced anti–B13 DSA (MFI 3000). This case raises some concerns: in this context, the use of IVIG in the treatment of CMV infection and AMR appears reasonable, in support of antiviral and immunosuppressive therapy.