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Acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) is a frequent complication associated with adverse outcomes and mortality. Various scores have been developed to predict this complication in the coronary setting. However, none have ever been tested in a large TAVI population. The present study aimed to evaluate the power of four (4) different scores in predicting AKI after TAVI.Overall, 1535 consecutive TAVI patients from the observational multicentric "Magna Graecia" TAVI registry were included in the analysis. Of the study population, 235 (15.31%) developed AKI early. The Mehran, William Beaumont Hospital, CRPatients who developed TAVI-related AKI had significantly higher absolute values of all risk scores than those who did not. Receiver operating characteristic analysis also showed a significant correlation between these four (4) scores and AKI, but without a significant difference among them all (p-value=0.176). Nevertheless, based on their area under the curve values (≤0.604 for all), none had adequate diagnostic accuracy in predicting TAVI-related AKI. Importantly, multivariate analysis identified myocardial revascularization close to the TAVI procedure and implantation of self-expanding prostheses, as well as atrial fibrillation, low-osmolar contrast media administration, corrected contrast medium volume, and any transfusion (p-value0.05 for all) as independent risk factors for AKI.Although high values of current AKI risk scores are significantly associated with the development of this complication, these are not sufficiently accurate. Further studies are needed so that a TAVI-dedicated AKI risk score may be created.

Background: Surgical mortality risk scores, even if not properly designed and rarely tested in the transcatheter aortic valve implantation (TAVI) setting, still guide the heart team in managing significant aortic stenosis. Methods: After splitting 1763 consecutive patients retrospectively based on their mortality risk thresholds, the composite endpoint early safety (ES) was adjudicated according to Valve Academic Research Consortium (VARC)-2 and -3 consensus documents. Results: ES incidence was higher if VARC-2 rather than VARC-3 defined. Despite only patients showing VARC-2 ES had significantly lower absolute values of all three main risk scores, these last still failed to foresee both VARC-2 and -3 ES in intermediate-risk patients. The receiver operating characteristic analysis also showed a significant correlation, but with poor diagnostic accuracy, among the three scores and only VARC-2 ES; moreover, the absence of VARC-2 ES and low-osmolar contrast media administration were identified as independent predictors of 1-year mortality and absence of VARC-3 ES, respectively. Finally, even a single complication included in the ES definition could significantly affect 1-year mortality. Conclusion: Currently, the most used mortality risk scores do not have adequate diagnostic accuracy in predicting ES after TAVI. The absence of VARC-2, instead of VARC-3, ES is an independent predictor of 1-year mortality.

Introduction Refractory angina (RA) is considered the end-stage of coronary artery disease, and often has no interventional treatment options. Coronary sinus Reducer (CSR) is a recent addition to the therapeutic arsenal, but its efficacy has only been evaluated on small populations. The RESOURCE registry provides further insights into this therapy. Methods The RESOURCE is an observational, retrospective registry that includes 658 patients with RA from 20 centers in Europe, United Kingdom and Israel. Prespecified endpoints were the amelioration of anginal symptoms evaluated with the Canadian Cardiovascular Society (CCS) score, the rates of procedural success and complications, and MACEs as composite of all-cause mortality, acute coronary syndromes, and stroke. Results At a median follow-up of 502 days (IQR 225–1091) after CSR implantation, 39.7% of patients improved by ≥2 CCS classes (primary endpoint), and 76% by ≥1 class. Procedural success was achieved in 96.7% of attempts, with 3% of procedures aborted mostly for unsuitable coronary sinus anatomy. Any complication occurred in 5.7% of procedures, but never required bailout surgery nor resulted in intra- or periprocedural death or myocardial infarction. One patient developed periprocedural stroke after inadvertent carotid artery puncture. At the last available follow-up, overall mortality and MACE were 10.4% and 14.6% respectively. At one, three and five years, mortality rate at Kaplan-Meier analysis was 4%, 13.7%, and 23.4% respectively. Conclusions CSR implantation is safe and reduces angina in patients with refractory angina.

The coronary sinus (CS) Reducer is a novel device designed for the management of patients with severe angina symptoms refractory to optimal medical therapy and not amenable to further revascularization. Aim of this study was to investigate the efficacy and the safety of the CS Reducer device in a real-world, multicenter, and country-level cohort of patients presenting with refractory angina pectoris. The study included patients affected by refractory angina pectoris who underwent CS Reducer implantation in 16 centers. Clinical follow-up was carried as per each center's protocol. One hundred eighty-seven patients were included. Technical and procedural success were achieved in 98% and 95%, respectively. Minor peri-procedural complications were recorded in 8 patients. During a median follow-up of 18.4 months, 135 (82.8%) patients demonstrated at least 1 CCS class reduction after Reducer implantation, and 80 (49%) patients at least 2 CCS class reduction. Mean CCS class improved from 3.05 ± 0.53 at baseline to 1.63 ± 0.98 at follow-up (p < 0.001). Treatment benefit was also reflected in a significant improvement in quality of life scores and in a reduction of the mean number of anti-ischemic drugs prescribed for patient. In conclusion, in this multicenter, country-level study, the implantation of CS Reducer in patients with refractory angina pectoris resulted to be safe and effective in reducing of angina pectoris and improving quality of life.

Surgical aortic valve replacement with a rapid deployment valve (RDV) is a relatively recent treatment option. The aim of this study was to compare the hemodynamic performance of balloon-expandable (BE)-RDVs and BE-transcatheter heart valves (THVs) in a high surgical risk and frail-elderly population.BE-THVs and BE-RDVs were implanted in 138 and 47 patients, respectively, all older than 75 years and with a Canadian Study of Health and Aging category of 5 or above. Echocardiographic assessment was performed at discharge and six months later.At discharge, transprosthetic pressure gradients and indexed effective orifice area (iEOA) were similar in both cohorts. At six-month follow-up, BE-RDVs showed lower peak (14.69 vs. 20.86 mmHg; p 0.001) and mean (7.82 vs. 11.83 mmHg; p 0.001) gradients, and larger iEOA (1.05 vs. 0.84 cmBE-RDVs showed better hemodynamic performance, especially when implanted in small annuli. Despite their worse baseline conditions, transcatheter patients still exhibited a greater improvement of their echocardiographic profile at mid-term follow-up.

Clinical trials offer new and potentially more effective therapeutic options for cancer patients and a potential cost-saving opportunity, especially considering that trial drugs are provided free-of-charge. The aim of this study was to analyse drug-related cost savings in clinical trials in a cancer institute over a 3 year period. The cost savings relate to the pharmaceutical expenditure of our centre, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori".We conducted a retrospective analysis of patients taking part in interventional clinical cancer trials approved by a local independent Ethics Committee between 1 January 2018 and 31 December 2020. The standard of care (SOC) was identified as the standard treatment that would have been offered to a patient if he/she had not been enrolled in the study. The sum of SOC costs of all patients represents the potential cost avoidance during the study period. Results were stratified by year, trial promoter, trial phase and tumour type. The same approach was used to perform a secondary analysis of compassionate use programmes.In the 3 year analysis, 1,257 patients were treated with experimental therapies in 244 clinical trials, of which 157 were profit and 87 academic. Results showed an overall cost savings of €13,266,518, more than 50% of which (€7,035,009) was related to phase III studies. Profit clinical trials generated €9,069,764 (68.4%) of the drug cost savings compared with €4,196,754 (31.6%) of academic studies. The stratification for tumour type was €3,552,592 (26.8%) genitourinary cancer, €3,268,074 (24.6%) melanoma, €2,574,127 (19.4%) haematological malignancies, €2,330,791 (17.6%) lung cancer, €728,149 (5.5%) gastrointestinal cancer, €557,608 (4.2%) rare tumours and €255,178 (1.9%) breast cancer. The secondary analysis on compassionate use included 122 patients involved in 28 different access programmes and revealed cost savings of €1,649,550.The results of our analysis point to the benefits of participating in and planning clinical trials for the public healthcare sector.

Introduction: Among the oncogene-addicted non-small cell lung cancer patients, those bearing ALK rearrangement can be currently treated with next-generation ALK inhibitors. Brigatinib was first use...

A comprehensive description of baseline characteristics, procedural features and outcomes related to the development of acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) is reported in our research paper (Impact of contrast medium osmolality on the risk of acute kidney injury after transcatheter aortic valve implantation: insights from the Magna Graecia TAVI registry. Int J Cardiol. DOI: 10.1016/j.ijcard.2020.12.049). Three Italian heart centers were involved in this multicentric observational study. Between March 2011 and February 2019, a total of 888 patients underwent TAVI; according to the inclusion and exclusion criteria, 697 patients were included in the post-hoc analysis. This Data in Brief paper aims to report demographic, clinical, laboratory, echocardiographic, intraprocedural, periprocedural, postprocedural and follow-up data; all of them were prospectively collected from each patient's health record, whereas the analysis was performed retrospectively. Targets of this data analysis were: 1) to evaluate the impact of contrast medium (CM) osmolality on TAVI-related AKI; 2) to identify the most of risk factors involved in the development of such complication, and consequently in the occurrence of 1-year mortality; 3) to estimate the impact of CM osmolality on AKI in specific patient subgroups.

Over the last few years, we assisted to an increasing knowledge about acute myeloid leukemia (AML) pathobiology. However, outcomes remain unsatisfactory particularly for adult patients over 60 years old. Not surprisingly several cases of therapy-related AML (tAML) and secondary AML, both characterized by poorer prognosis, are more common in older population. For several decades initial therapy for AML remained unchanged and typically treatment consisted of an anthracycline combined with continuous infusion of cytarabine for 7 days, the so-called "7+3" standard regimen. The efforts made by the researchers to improve this standard schedule, have led to only modest improvement in the response rate (RR) but no change in overall survival (OS), until the recent evolution seen with new target specific mutation therapies. In 2017, a new liposomal-encapsulated formulation with daunorubicin and cytarabine (CPX-351) was approved by the US Food and Drug Administration for the treatment of newly diagnosed tAML or AML with myelodysplasia-related changes (AML-MRCs). Based on the findings that ratiometric delivery may be more effective than administration of either drug at their maximum tolerated dose (MTD), CPX-351 was designed to deliver a fixed 5:1 molar ratio of the two molecules historically used in the standard "7+3" regimen, cytarabine and daunorubicin respectively. CPX-351 did show improvements of overall survival compared to traditional "7+3" in newly diagnosed secondary and therapy-related AML in adult patients. However, questions remain regarding how to select across AML patient subgroups to maximize the clinical benefit. Possible future directions include evaluating CPX-351 dose intensification, combining this liposomal formulation with targeted therapies and not least important a better understanding about the mechanism of improved responses in tAML and AML-MRC, two entities recognized to be less chemo-sensitive than other hematologic malignancies. In summary, CPX-351 offers finally something new in the landscape of AML therapy. Herein we will review the rationale behind this new drug product development, the main pharmacological characteristics, and discuss the results of clinical trials that led to its FDA approval at first and by EMA in 2018.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy, characterized by poor prognosis if treated with conventional therapy. Allogenic hematologic stem cell transplant can improve survival and can be curative, but it is available in a small percentage of patients given that the median age at diagnosis is 70 years. In this scenario it is assumed that only the development of precision medicine-driven therapy will change BPDCN patient prognosis. CD123 (the α-subunit of interleukin (IL)-3 receptor) is over-expressed on BPDCN cells surface and seems to be the ideal marker to develop antibody-based therapies. Tagraxofusp (Elzonris®), a recombinant immunotoxin consisting of human interleukin-3 fused to a truncated diphtheria toxin, has been approved by FDA in December 2018 for the treatment of BPDCN in adult and pediatric patients. tagraxofusp has shown promising clinical activity, with a high overall response rate and quite manageable safety profile even in elderly patients. It seems to improve overall survival too, but comparative trials are necessary to confirm this. Adverse events are commonly reported and the most important are transaminitis, thrombocytopenia and capillary leak syndrome (CLS). Therefore, to prevent the onset of severe CLS is recommended to reserve tagraxofusp for patients with preserved hepatic and cardiac functions, and to strictly observe serum albumin level. Further studies are required to resolve many several unanswered questions about tagraxofusp. In this review, we will resume and discuss pharmacological characteristic of tagraxofusp, results of clinical trials leading to its approval by FDA in 2018 and future perspectives about its use in BPDCN and other hematological malignancies.

Background: Acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) is frequent and associated with adverse outcomes and mortality; to date, in such setting of patients there is no consistent evidence that either low-osmolar contrast media (LOCM) or iso‐osmolar contrast medium (IOCM) are superior to the other in terms of renal safety. Methods: 697 consecutive patients not in hemodialysis treatment who underwent TAVI (327 males, mean age 81.01 ± 5.75 years, mean european system for cardiac operative risk evaluation II 6.17 ± 0.23%) were enrolled. According to osmolality of the different iodinated CM, the population was divided in 2 groups: IOCM (n = 370) and LOCM group (n = 327). Preoperatively, 40.54% of patients in IOCM vs 39.14% in LOCM group (p = 0.765) suffered from chronic kidney disease (CKD). Results: The incidence of AKI was significantly lower with IOCM (9.73%) than with LOCM (15.90%; p = 0.02), and such significant difference (p < 0.001) in postprocedural change of renal function parameters persisted at discharge too. The incidence of AKI was also significantly lower with IOCM in younger patients, without diabetes, anemia, coronary artery disease history, CKD, chronic or persistent atrial fibrillation, left ventricular ejection fraction ≤35%, and in patients with low operative mortality risk scores, receiving lower amounts of dye (p < 0.05 for all). Importantly, multivariate analysis identified LOCM administration as an independent risk factor for both AKI (p = 0.006) and 1-year mortality (p = 0.001). Conclusions: The use of IOCM have a favorable impact on renal function with respect to LOCM, but it should be considered especially for TAVI patients at lower AKI risk.

Immunotherapy directed at the programmed cell death-1 receptor (PD-1) or its ligand PD-L1 has proven effective in solid malignancies such as melanoma, non-small cell lung cancer (NSCLC), urothelial cancer, renal cell carcinoma, and head and neck cancer. Compared with cytotoxic chemotherapy, radiotherapy, or molecular targeted agents, immunotherapy is an innovative strategy for treating malignancies, with durable clinical responses and manageable adverse events. Thymic carcinomas are extremely rare, constituting only 0.06% of all malignancies, are much more aggressive tumours than thymomas and have a worse prognosis. Nowadays, first line platinum-based chemotherapy for metastatic tumours are the cornerstone of treatment. However, the results of further therapeutic lines for metastatic or relapsed thymic carcinoma are unsatisfactory, with no regimen showing a consistent benefit. Moreover, the rarity of these tumours makes it difficult to carry out clinical trials. Herein we report a remarkable result of 1 year stable disease with good quality of life and no side effects obtained from the use of immunotherapy with pembrolizumab in a case of heavily pre-treated squamous cell thymic carcinoma and cardiac impairment. We also include a literature review of clinical trials on PD-1/PD-L1 inhibitors for the treatment of thymic epithelial cancers, taking a close look at cardiac toxicity.

OBJECTIVES The aim of this observational study was to determine the benefits of the novel, orally delivered P2Y12 -inhibitors (Is) in terms of angiographic endpoints and in relation to the time of the loading dose (LD) administration. BACKGROUND The goal of ST-elevation myocardial infarction (STEMI) treatment is timely reperfusion. The P2Y12 -Is prasugrel and ticagrelor have improved the angiographic outcome of primary percutaneous coronary intervention (pPCI) and patients' prognosis. However, their onset of action is impaired in STEMI and delayed by their oral administration. METHODS The 328 eligible patients with STEMI consecutively referred for pPCI were divided into three groups depending on the interval of "P2Y12 -I LD administration-to-balloon time": Group 2 included patients that received P2Y12 -I LD at least 60 min prior to pPCI, Group 1 within 60 min prior to pPCI, and Group 0 at the moment of pPCI. Angiographic, clinical, and biochemical parameters were evaluated. Pre- and post-pPCI TIMI flow grade (TFG) and ST resolution (STR) were used as outcome measures to determine efficacy and optimal timing of pretreatment. RESULTS Pre-pPCI TFG improved with increasing P2Y12 -I LD administration-to-balloon time; pre-PCI TFG 0/1 was 74.5% in Group 0, 65.5% in Group 1 and 54.9% in Group 2 (P

Takotsubo cardiomyopathy (TTC) is a form of acute left ventricular dysfunction usually reversible and with favorable prognosis. Ventricular septal perforation (VSP) is a very rare life-threatening complication. Percutaneous closure of VSP, despite being challenging, is a possible alternative to surgical repair. We present the first case of an 84-year-old patient with a TTC-related VSP treated by percutaneous approach. The case highlights the need of reconsidering the worldwide accepted consideration of TTC as benignant and allows some speculations on the optimal management of VSP in terms of timing, patient selection and possible alternative interventions.

The aim of this observational study was to determine the benefits of the novel, orally delivered P2YThe goal of ST-elevation myocardial infarction (STEMI) treatment is timely reperfusion. The P2YThe 328 eligible patients with STEMI consecutively referred for pPCI were divided into three groups depending on the interval of "P2YPre-pPCI TFG improved with increasing P2YThis observational study suggests that the angiographic benefit of P2Y

Hyperglycemia is frequent in patients with ST elevation myocardial infarction (STEMI) and is associated with adverse outcome. Aim of our study was to evaluate the correlation between admission plasma glucose level (PGL) and coronary arteries flow velocity.We enrolled 149 STEMI patients successfully treated with primary percutaneous coronary intervention (pPCI). The study population was divided into two groups based on PGL (or140 mg/dl) and on history of diabetes, and the groups compared in terms of corrected TIMI frame count (cTFC).Hyperglycemic patients had a significantly higher cTFC in both the culprit (p 0.0001) and non-culprit vessel (p: 0.0002); diabetes history impairs as well cTFC of the culprit (p 0.0001) and non-culprit vessel (p: 0.0001). Within the subpopulation of diabetic patients hyperglycemic ones showed higher cTFC in both the culprit (p 0.0013) and non-culprit vessel (p: 0.0006). Moreover in the whole population cTFC values of both arteries increase linearly with the increment of admission PGL.Admission PGL affects coronary flow of both culprit and non-culprit vessel. The impairment of coronary flow is also demonstrated in known diabetic patients, suggesting to consider hyperglycemia an additional risk factor. We finally demonstrated for the first time a positive linear relationship between PGL and cTFC.

Acute lower extremities peripheral artery disease represents a clinical emergency. Peripheral artery disease incidence ranges from 2.5 to 22% and has progressively increased due to the world population aging phenomenon and associates with coronary artery disease with a rate of 40–60%. The authors present the case of an 89-year-old man coming to their attention with acute lower extremities ischemia and unstable angina. Despite the short-to-midterm favorable outcome, doubts remain about the opportunity of treating ‘very old’ patients. The lack of dedicated randomized trials and of defined guidelines is a problem the scientific community needs to face considering that patients over 85 years represent a raising quote of the whole population of our catheterization laboratories.

Mitral regurgitation (MR) is the most frequent valvulopathy in the general population with an incidence that grows with age and is associated with a poor prognosis. Regardless of its primary cause, which can be both ischaemic and non-ischaemic cardiomyopathy, it finally activates a self-feeding process. Due to the complexity of mitral valve (MV) apparatus and its interaction with the myocardium, even the diagnosis could represent a challenge for physicians. Higher technological instruments such as 3D echocardiography and cardiac magnetic resonance could play an important role in the evaluation of MV. In this paper we reviewed the most salient aspects of functional MR pathophysiology as well as the current diagnostic methods. The management of functional mitral regurgitation (FMR) is even more challenging and controversial; the optimal approach, timing, and effectiveness of interventions are still debated. Treatment of FMR begins with optimal medical therapy for left ventricular dysfunction, including cardiac resynchronisation when indicated. While functional improvement after surgery is well established, the benefits in terms of survival are still questionable. Moreover, in patients with high perioperative risk there is a growing interest in emerging percutaneous techniques. Among a variety of medical, surgical, and percutaneous opportunities, authors support an accurate case-by-case evaluation to find a tailored and stepwise treatment according to anatomical features and patient comorbidities.

Mitral regurgitation (MR) is the most frequent valvulopathy in the general population with an incidence that grows with age and is associated with a poor prognosis. Regardless of its primary cause, which can be both ischaemic and non-ischaemic cardiomyopathy, it finally activates a self-feeding process. Due to the complexity of mitral valve (MV) apparatus and its interaction with the myocardium, even the diagnosis could represent a challenge for physicians. Higher technological instruments such as 3D echocardiography and cardiac magnetic resonance could play an important role in the evaluation of MV. In this paper we reviewed the most salient aspects of functional MR pathophysiology as well as the current diagnostic methods. The management of functional mitral regurgitation (FMR) is even more challenging and controversial; the optimal approach, timing, and effectiveness of interventions are still debated. Treatment of FMR begins with optimal medical therapy for left ventricular dysfunction, including cardiac resynchronisation when indicated. While functional improvement after surgery is well established, the benefits in terms of survival are still questionable. Moreover, in patients with high perioperative risk there is a growing interest in emerging percutaneous techniques. Among a variety of medical, surgical, and percutaneous opportunities, authors support an accurate case-by-case evaluation to find a tailored and stepwise treatment according to anatomical features and patient comorbidities.

Dual antiplatelet therapy improves angiographic results of primary percutaneous coronary intervention (pPCI) in patients with STEMI. The new oral P2Y12 inhibitors (P2Y12-I) prasugrel and ticagrelor are the gold-standard drugs because of a faster and more intense effect when compared to clopidogrel.