Three-dimensional printed models as an effective tool for the management of complex congenital heart disease.

Introduction: Three-dimensional printed models are widely used in the medical field for surgical and interventional planning. In the context of complex cardiovascular defects such as pediatric congenital heart diseases (CHDs), the adoption of 3D printed models could be an effective tool to improve decision-making. In this paper, an investigation was conducted into the characteristics of 3D printed models and their added value in understanding and managing complex pediatric congenital heart disease, also considering the associated cost. Methods: Volumetric MRI and CT images of subjects with complex CHDs were retrospectively segmented, and the associated 3D models were reconstructed. Different 3D printing technologies and materials were evaluated to obtain the 3D printed models of cardiac structures. An evaluation of time and costs associated with the 3D printing procedure was also provided. A two-level 3D printed model assessment was carried out to investigate the most suitable 3D printing technology for the management of complex CHDs and the effectiveness of 3D printed models in the pre-surgical planning and surgical strategies' simulations. Results: Among the different techniques, selective laser sintering resulted to be the most suitable due to its reduced time and cost and for the positive clinical feedback (procedure simulation, surface finish, and reproduction of details). Conclusion: The adoption of 3D printed models contributes as an effective tool in the management of complex CHDs, enabling planning and simulations of surgical procedures in a safer way.

Role of Imaging in Cardiomyopathies.

Imaging has a central role in the diagnosis, classification, and clinical management of cardiomyopathies. While echocardiography is the first-line technique, given its wide availability and safety, advanced imaging, including cardiovascular magnetic resonance (CMR), nuclear medicine and CT, is increasingly needed to refine the diagnosis or guide therapeutic decision-making. In selected cases, such as in transthyretin-related cardiac amyloidosis or in arrhythmogenic cardiomyopathy, the demonstration of histological features of the disease can be avoided when typical findings are observed at bone-tracer scintigraphy or CMR, respectively. Findings from imaging techniques should always be integrated with data from the clinical, electrocardiographic, biomarker, genetic and functional evaluation to pursue an individualised approach to patients with cardiomyopathy.

Advantages of Photon-Counting Detector CT in Aortic Imaging.

Photon-counting Computed Tomography (PCCT) is a promising imaging technique. Using detectors that count the number and energy of photons in multiple bins, PCCT offers several advantages over conventional CT, including a higher image quality, reduced contrast agent volume, radiation doses, and artifacts. Although PCCT is well established for cardiac imaging in assessing coronary artery disease, its application in aortic imaging remains limited. This review summarizes the available literature and provides an overview of the current use of PCCT for the diagnosis of aortic imaging, focusing mainly on endoleaks detection and characterization after endovascular aneurysm repair (EVAR), contrast dose volume, and radiation exposure reduction, particularly in patients with chronic kidney disease and in those requiring follow-up CT.

Etiology, clinical presentation, and management of left main coronary artery aneurysms.

BACKGROUND AND AIM OF THE STUDY: The widespread use of noninvasive/invasive coronary imaging increased the probability of recognition of coronary aneurysms. Left main coronary aneurysms (LMCA), though rare, are potentially life-threatening but in the absence of controlled studies, guidelines do not provide any specific recommendation for their management. We, therefore, aimed to investigate the epidemiology, clinical presentation, therapeutic strategies, and prognostic implication of LMCA. METHODS: A systematic review of the literature was performed to retrieve all the reported cases of LMCA as of December 2021, which were summarized and classified according to their etiology, clinical presentation, and therapeutic management. RESULTS: Out of 1997 works retrieved, 180 studies were analyzed, describing 209 LMCA cases (aged 51 ± 19 years, 68% males). Atherosclerosis was the most common etiology (40%), followed by inflammatory (12%), congenital (9%), or degenerative (6%) conditions. Stable angina (43%) and acute coronary syndromes (32%) were more often the first clinical manifestations, while 29 (14%) LMCA were incidental findings. Most cases were treated surgically (53%), while percutaneous intervention was rarely adopted (7%). Data about antithrombotic therapies were scarce and heterogeneous. Finally, when longitudinal data were reported (n = 81), LMCA resulted associated with a severe prognosis, with a 15% mortality over an 8-month median follow-up. CONCLUSIONS: LMCA are most frequently, but not exclusively, caused by advanced atherosclerosis. Irrespective of their etiology and clinical presentation, LMCA may be associated with high short-term mortality. In absence of controlled studies, a careful evaluation of each case is warranted to optimize therapeutic strategies.

Appropriateness criteria for the use of cardiac computed tomography, SIC-SIRM part 2: acute chest pain evaluation; stent and coronary artery bypass graft patency evaluation; planning of coronary revascularization and transcatheter valve procedures; cardiomyopathies, electrophysiological applications, cardiac masses, cardio-oncology and pericardial diseases evaluation.

In the past 20 years, cardiac computed tomography (CCT) has become a pivotal technique for the noninvasive diagnostic workup of coronary and cardiac diseases. Continuous technical and methodological improvements, combined with fast growing scientific evidence, have progressively expanded the clinical role of CCT. Randomized clinical trials documented the value of CCT in increasing the cost-effectiveness of the management of patients with acute chest pain presenting in the emergency department, also during the pandemic. Beyond the evaluation of stents and surgical graft patency, the anatomical and functional coronary imaging have the potential to guide treatment decision-making and planning for complex left main and three-vessel coronary disease. Furthermore, there has been an increasing demand to use CCT for preinterventional planning in minimally invasive procedures, such as transcatheter valve implantation and mitral valve repair. Yet, the use of CCT as a roadmap for tailored electrophysiological procedures has gained increasing importance to assure maximum success. In the meantime, innovations and advanced postprocessing tools have generated new potential applications of CCT from the simple coronary anatomy to the complete assessment of structural, functional and pathophysiological biomarkers of cardiac disease. In this complex and revolutionary scenario, it is urgently needed to provide an updated guide for the appropriate use of CCT in different clinical settings. This manuscript, endorsed by the Italian Society of Cardiology (SIC) and the Italian Society of Medical and Interventional Radiology (SIRM), represents the second of two consensus documents collecting the expert opinion of cardiologists and radiologists about current appropriate use of CCT.

Big gamma-glutamyltransferase is associated with epicardial fat volume and cardiovascular outcome in the general population.

AIMS: Gamma-glutamyltransferase (GGT) has been recognized as a cardiovascular risk factor, and its highest molecular weight fraction [big GGT (b-GGT)] is found in vulnerable atherosclerotic plaques. We explored the relationship between b-GGT, computed tomography findings, and long-term outcomes in the general population. METHODS AND RESULTS: Between May 2010 and October 2011, subjects aged 45-75 years living in a Tuscan city and without known cardiac disease were screened. The primary endpoint was a composite of cardiovascular death or acute coronary syndrome requiring urgent coronary revascularization. Gamma-glutamyltransferase fractions were available in 898 subjects [median age 65 years (25th-75th percentile 55-70), 46% men]. Median plasma GGT was 20 IU (15-29), and b-GGT was 2.28 (1.28-4.17). Coronary artery calcium (CAC) score values were 0 (0-60), and the volume of pro-atherogenic epicardial fat was 155 mL (114-204). In a model including age, sex, low-density lipoprotein (LDL) cholesterol, current or previous smoking status, hypertension, diabetes, obesity, b-GGT independently predicted epicardial fat volume (EFV) (r = 0.162, P < 0.001), but not CAC (P = 0.198). Over a 10.3-year follow-up (9.6-10.8), 27 subjects (3%) experienced the primary endpoint. We evaluated couples of variables including b-GGT and a cardiovascular risk factor, CAC or EFV. Big GGT yielded independent prognostic significance from age, LDL cholesterol, current or previous smoking status, hypertension, diabetes, obesity, but not CAC or EFV. Conversely, GGT predicted the primary endpoint even independently from CAC and EFV. CONCLUSION: Big GGT seemed at least as predictive as the commonly available GGT assay; therefore, the need for b-GGT rather than GGT measurement should be carefully examined.

Transcatheter Treatment of "Complex" Aortic Coarctation Guided by Printed 3D Model.

The transcatheter approach is nowadays considered a cost-effective alternative to surgery in adults with "complex" aortic coarctation. The printed 3D model was crucial in planning transcatheter treatment of a complex case of postsurgical aortic re-coarctation, due to coexistence of transverse aortic arch stenosis and pseudoaneurysm as well as aneurysm of the descending aorta. (Level of Difficulty: Advanced.).

SIRM-SIC appropriateness criteria for the use of Cardiac Computed Tomography. Part 1: Congenital heart diseases, primary prevention, risk assessment before surgery, suspected CAD in symptomatic patients, plaque and epicardial adipose tissue characterization, and functional assessment of stenosis.

In the past 20 years, Cardiac Computed Tomography (CCT) has become a pivotal technique for the noninvasive diagnostic work-up of coronary and cardiac diseases. Continuous technical and methodological improvements, combined with fast growing scientific evidence, have progressively expanded the clinical role of CCT. Recent large multicenter randomized clinical trials documented the high prognostic value of CCT and its capability to increase the cost-effectiveness of the management of patients with suspected CAD. In the meantime, CCT, initially perceived as a simple non-invasive technique for studying coronary anatomy, has transformed into a multiparametric "one-stop-shop" approach able to investigate the heart in a comprehensive way, including functional, structural and pathophysiological biomarkers. In this complex and revolutionary scenario, it is urgently needed to provide an updated guide for the appropriate use of CCT in different clinical settings. This manuscript, endorsed by the Italian Society of Medical and Interventional Radiology (SIRM) and by the Italian Society of Cardiology (SIC), represents the first of two consensus documents collecting the expert opinion of Radiologists and Cardiologists about current appropriate use of CCT.

INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors: a multicenter prospective observational study (INVIDIa-2).

BACKGROUND: Until now, no robust data supported the efficacy, safety and recommendation for influenza vaccination in patients with cancer receiving immune checkpoint inhibitors (ICIs). METHODS: The prospective multicenter observational INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors (INVIDIa-2) study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving ICIs, enrolled in 82 Italian centers from October 2019 to January 2020. The primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020. Secondary endpoints regarded ILI severity and vaccine safety. RESULTS: The study enrolled 1279 patients; 1188 patients were evaluable for the primary endpoint analysis. Of them, 48.9% (581) received influenza vaccination. The overall ILI incidence was 8.2% (98 patients). Vaccinated patients were significantly more frequently elderly (p<0.0001), males (p=0.004), with poor European Cooperative Oncology Group performance status (p=0.009), affected by lung cancer (p=0.01), and by other non-cancer comorbidities (p<0.0001) when compared with unvaccinated. ILI incidence was not different basing on influenza vaccination: the time-to-ILI was similar in vaccinated and unvaccinated patients (p=0.62). ILI complications were significantly less frequent for patients receiving the vaccination (11.8% vs 38.3% in unvaccinated, p=0.002). ILI-related intravenous therapies were significantly less frequent in vaccinated patients than in unvaccinated (11.8% vs 29.8%, p=0.027). ILI lethality was, respectively, 0% in vaccinated and 4.3% in unvaccinated patients. Vaccine-related adverse events were rare and mild (1.5%, grades 1-2). CONCLUSION: The INVIDIa-2 study results support a positive recommendation for influenza vaccination in patients with advanced cancer receiving immunotherapy.

Clinical research activities during COVID-19: the point of view of a promoter of academic clinical trials.

BACKGROUND: During the COVID-19 emergency, IRST IRCCS, an Italian cancer research institute and promoter of no profit clinical studies, adapted its activities and procedures as per European and national guidelines to maintain a high standard of clinical trials, uphold participant safety and guarantee the robustness and reliability of the data collected. This study presents the measures adopted by our institute with the aim of providing information that could be useful to other academic centers promoting clinical trials during the pandemic. MAIN TEXT: After an in-depth analysis of European and Italian guidelines and consultation and analysis of publications regarding the actions implemented by international no profit clinical trial promoters during the emergency, we monitored the way in which the institute managed clinical trials, verifying compliance with regulatory guidelines and clinical procedures, and evaluating screening and recruitment trends in studies. During the pandemic, our center activated a new clinical trial for the treatment of patients with COVID-19. A number of procedural changes in clinical trials were also authorized through notified amendments, in accordance with Italian Medicines Agency (AIFA) guidelines. Patient screening and enrolment was not interrupted in any site participating in multicenter interventional clinical trials on drugs. The institute provided clear indications about essential procedures to be followed, identifying those that could be postponed or carried out by telephone/teleconference. All external sites were monitored remotely, avoiding on-site visits. Although home-working was encouraged, the presence of staff in the central office was also guaranteed to ensure the continuity of promoter activities. CONCLUSIONS: Some measures adopted by IRST could also be effective outside of the COVID-19 period, e.g. numerous activities relating to clinical trial management could be performed on a home-working basis, using suitable digital technologies. In the future, electronic medical records and shared guidelines will be essential for the correct identification and management of trial risks, including the protection of the rights and privacy of subjects taking part. Promoter supervision could be increased by implementing centralized monitoring tools to guarantee data quality. Closer collaboration between promoters and local study staff is needed to optimize trial management.

Pitfalls in surgical repair of Fallot's tetralogy: The "ventricular subaortic pouch".

Fallot-type ventricular septal defect (VSD) is characterized by anterior malalignment of the outlet septum with variable degree of aortic dextroposition. Correct identification of the borders of the defect is crucial to achieve an optimal surgical repair. We describe a particular postsurgical lesion, identified by cardiac magnetic resonance and cardiac computed tomography, which results from an improper surgical closure technique of anterior malaligned VSD. Based on its anatomical features we defined this entity "subaortic pouch." A comprehensive description of this defect is here provided along with an in-depth analysis of the proper operative technique for Fallot-type VSD repair.

3D model-guided transcatheter closure of left ventricular pseudoaneurysm: a case series.

Left ventricular pseudoaneurysm (LVPsA) is a rare complication of myocardial infarction, cardiac surgery, chest trauma, infection or transcatheter interventions. It may cause arrhythmias, mass effect, thromboembolism and life-threatening rupture. The transcatheter approach is nowadays considered a cost-effective alternative to surgery. In this setting, 3D printing could be an emerging, powerful tool to plan transcatheter closure and choose the best occluding device. This study reports on three cases of complex LVPsA successfully treated by transcatheter device implantation guided by printed 3D heart models.

Technical development in cardiac CT: current standards and future improvements-a narrative review.

Non-invasive depiction of coronary arteries has been a great challenge for imaging specialists since the introduction of computed tomography (CT). Technological development together with improvements in spatial, temporal, and contrast resolution, progressively allowed implementation of the current clinical role of the CT assessment of coronary arteries. Several technological evolutions including hardware and software solutions of CT scanners have been developed to improve spatial and temporal resolution. The main challenges of cardiac computed tomography (CCT) are currently plaque characterization, functional assessment of stenosis and radiation dose reduction. In this review, we will discuss current standards and future improvements in CCT.

Symptomatic COVID-19 in advanced-cancer patients treated with immune-checkpoint inhibitors: prospective analysis from a multicentre observational trial by FICOG.

BACKGROUND: This prospective, multicentre, observational INVIDIa-2 study is investigating the clinical efficacy of influenza vaccination in advanced-cancer patients receiving immune-checkpoint inhibitors (ICIs), enrolled in 82 Italian centres, from October 2019 to January 2020. The primary endpoint was the incidence of influenza-like illness (ILI) until 30 April 2020. All the ILI episodes, laboratory tests, complications, hospitalizations and pneumonitis were recorded. Therefore, the study prospectively recorded all the COVID-19 ILI events. PATIENTS AND METHODS: Patients were included in this non-prespecified COVID-19 analysis, if alive on 31 January 2020, when the Italian government declared the national emergency. The prevalence of confirmed COVID-19 cases was detected as ILI episode with laboratory confirmation of SARS-CoV-2. Cases with clinical-radiological diagnosis of COVID-19 (COVID-like ILIs), were also reported. RESULTS: Out of 1257 enrolled patients, 955 matched the inclusion criteria for this unplanned analysis. From 31 January to 30 April 2020, 66 patients had ILI: 9 of 955 cases were confirmed COVID-19 ILIs, with prevalence of 0.9% [95% confidence interval (CI): 0.3-2.4], a hospitalization rate of 100% and a mortality rate of 77.8%. Including 5 COVID-like ILIs, the overall COVID-19 prevalence was 1.5% (95% CI: 0.5-3.1), with 100% hospitalization and 64% mortality. The presence of elderly, males and comorbidities was significantly higher among patients vaccinated against influenza versus unvaccinated (p = 0.009, p < 0.0001, p < 0.0001). Overall COVID-19 prevalence was 1.2% for vaccinated (six of 482 cases, all confirmed) and 1.7% for unvaccinated (8 of 473, 3 confirmed COVID-19 and 5 COVID-like), p = 0.52. The difference remained non-significant, considering confirmed COVID-19 only (p = 0.33). CONCLUSION: COVID-19 has a meaningful clinical impact on the cancer-patient population receiving ICIs, with high prevalence, hospitalization and an alarming mortality rate among symptomatic cases. Influenza vaccination does not protect from SARS-CoV-2 infection.

Clinical impact of COVID-19 in a single-center cohort of a prospective study in cancer patients receiving immunotherapy.

Aim: Evaluating the incidence and course of COVID-19 in cancer patients treated with immunotherapy. Patients & methods: We reported the influenza-like illness events with diagnosis of COVID-19 within the patient cohort enrolled in the prospective observational multicenter INVIDIa-2 study in the single center of Parma. Results: Among 53 patients, eight experienced influenza-like illness during the influenza season 2019/2020, and three of them had diagnosis of COVID-19. They were males, elderly, with cardiovascular disease. Radiological features of COVID-19 pneumonitis were found in all of three cases, although the pharyngeal swab resulted positive in only two. Two of these three patients died due to respiratory failure. Conclusion: Cancer patients are at high risk of severe events from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

What Is Hidden Behind Inferior Negative T Waves: Multiple Cardiac Glomangiomas.

Negative T waves in the inferior leads in an asymptomatic 17-year-old female patient prompted a diagnostic evaluation disclosing the presence of multiple cardiac glomangiomas. The combination of different imaging modalities (echocardiography, magnetic resonance, and positron emission tomography/computed tomography) and myocardial biopsy was crucial to establishing the correct diagnosis. (Level of Difficulty: Advanced.).