Multimodality imaging in cardio-oncology: the added value of CMR and CCTA.

During the last 30 years, we have assisted to a great implementation in anticancer treatment with a subsequent increase of cancer survivors and decreased mortality. This has led to an ongoing interest about the possible therapy-related side-effects and their management to better guide patients therapy and surveillance in the chronic and long-term setting. As a consequence cardio-oncology was born, involving several different specialties, among which radiology plays a relevant role. Till the end of August 2022, when European Society of Cardiology (ESC) developed the first guidelines on cardio-oncology, no general indications existed to guide diagnosis and treatment of cancer therapy-related cardiovascular toxicity (CTR-CVT). They defined multimodality imaging role in primary and secondary prevention strategies, cancer treatment surveillance and early CTR-CVT identification and management. Cardiac computed tomography angiography (CCTA) has acquired a central role in coronary assessment, as far as coronary artery disease (CAD) exclusion is concerned; but on the side of this well-known application, it also started to be considered in left ventricular function evaluation, interstitial fibrosis quantification and cardiac perfusion studies. Cardiac magnetic resonance (CMR), instead, has been acknowledged as the gold standard alternative to trans-thoracic echocardiography (TTE) poor acoustic window in quantification of heart function and strain modifications, as well as pre- and post-contrast tissue characterization by means of T1-T2 mapping, early Gadolinium enhancement (EGE), late Gadolinium enhancement (LGE) and extracellular volume (ECV) evaluation. Our review is intended to provide a focus on the actual role of CMR and CCTA in the setting of a better understanding of cardiotoxicity and to draw some possible future directions of cardiac imaging in this field, starting from the recently published ESC guidelines.

Nebivolol versus placebo in patients undergoing anthracyclines (CONTROL Trial): rationale and study design.

AIMS: Anthracyclines are the chemotherapeutic agents most frequently associated with cardiotoxicity, while remaining widely used. Different neurohormonal blockers have been tested as a primary prevention strategy to prevent or attenuate the onset of cardiotoxicity, with mixed results. However, prior studies were often limited by a nonblinded design and an assessment of cardiac function based only on echocardiographic imaging. Moreover, on the basis of an improved mechanistic understanding of anthracycline cardiotoxicity mechanisms, new therapeutic strategies have been proposed. Among cardioprotective drugs, nebivolol might be able to prevent the cardiotoxic effects of anthracyclines, through its protective properties towards the myocardium, endothelium, and cardiac mitochondria. This study aims to evaluate the cardioprotective effects of the beta blocker nebivolol in a prospective, placebo-controlled, superiority randomized trial in patients with breast cancer or diffuse large B cell lymphoma (DLBCL) who have a normal cardiac function and will receive anthracyclines as part of their first-line chemotherapy programme. METHODS: The CONTROL trial is a randomized, placebo-controlled, double-blinded, superiority trial. Patients with breast cancer or a DLBCL, with a normal cardiac function as assessed by echocardiography, scheduled for treatment with anthracyclines as part of their first-line chemotherapy programme will be randomized 1 : 1 to nebivolol 5 mg once daily (o.d.) or placebo. Patients will be examined with cardiological assessment, echocardiography and cardiac biomarkers at baseline, 1 month, 6 months and 12 months. A cardiac magnetic resonance (CMR) assessment will be performed at baseline and at 12 months. The primary end point is defined as left ventricular ejection fraction reduction assessed by CMR at 12 months of follow-up. CONCLUSION: The CONTROL trial is designed to provide evidence to assess the cardioprotective role of nebivolol in patients undergoing chemotherapy with anthracyclines. CLINICAL TRIAL REGISTRATION: The study is registered in the EudraCT registry (number: 2017-004618-24) and in the ClinicalTrials.gov registry (identifier: NCT05728632).

Similar clinical and radiographic outcomes after two different hypoallergenic medial unicompartmental knee in patients with metal allergy.

BACKGROUND: The purpose in the present study was to compare clinical and radiological outcomes of patients who had undergone a mobile-bearing unicompartmental knee arthroplasty (UKA) with either titanium niobium nitride (TiNbN) alloy implants or with fixed-bearing oxidized zirconium alloy implants. METHODS: The records of two consecutive cohorts for a total of 86 hypoallergenic implants were prospectively analyzed. The first cohort consisted of 49 consecutive implantations of the hypoallergenic UKA Journey Uni Oxinium (Ox Group), while the second consisted of 37 consecutive series of UKA Oxford (TiNbN Group). All patients were evaluated by two independent surgeons who were not involved in the index surgery. The clinical evaluation consisted of evaluating each patient's Oxford Knee Score and Knee Society Score day before surgery (T0), and with two consecutive follow-ups at T1 (minimum follow-up 9 months) and T2 (minimum follow-up 24 months). RESULTS: The two groups were homogeneous in all preoperative values, except Body Mass Index (BMI) and duration of final follow-up [both statistically higher (p < 0.05) in the TiNbN group]. Both groups showed a clinically significant improvement for all scores at final follow-up (p < 0.05). The only differences between the two groups involved a higher pre-operative Oxford Score in TiNbN group (p = 0.031), and different tibial and femoral angles at the final follow-up. CONCLUSIONS: Both TiNbN and Oxinium UKA procedures enabled patients from good to excellent clinical and radiographic outcomes after the final follow-up, regardless of the age, gender, BMI bearing type, and implant size. LEVEL OF EVIDENCE: LEVEL II: Comparative study.

Value of 3D echocardiography in the diagnosis of arrhythmogenic right ventricular cardiomyopathy.

AIMS: The 2010 Task Force Criteria (TFC) require that both right ventricular (RV) regional wall-motion abnormalities (WMA) and specific RV size cut-offs be met in order to fulfil one of the major criterion for arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis. Currently, 2D echocardiography (2DE) and cardiovascular magnetic resonance imaging (cMRI) are used to determine if these criteria are met. Little is known about the diagnostic value of 3D echocardiography (3DE) in ARVC. The aim of this study was to determine whether a combination of 2DE-3DE is non-inferior to the currently used 2DE-cMRI combination in the diagnosis of patients with ARVC. METHODS AND RESULTS: Thirty-nine individuals (47±15 years) with suspected ARVC underwent evaluation of the RV with cMRI, 2DE, and 3DE. 3DE and cMRI were independently used to obtain RV volumes, ejection fraction (EF) and determine the presence of segmental RV WMA. Studies were blindly classified as meeting criteria for ARVC in accordance with the 2010 TFC. Kappa statistics were used to test the concordance between 2DE-cMRI and 2DE-3DE approaches. Using the 2DE-cMRI approach, 3/39 were not affected, 5/39 possible, 8/39 borderline, and 23/39 definite ARVC. The proposed 2DE-3DE approach yielded 5/39 not affected, 7/39 possible, 8/39 borderline, and 19/39 definite diagnoses. The two approaches were highly concordant (k = 0.71; 95% confidence interval: 0.44-0.84). Although 3DE underestimated RV volumes in comparison with cMRI, interfering, in some instances with the fulfilment of a major criterion, it was able to identify more RV WMA (28/39) than 2DE (11/39), with a detection-rate comparable to cMRI (33/39) highlighting a unique advantage. CONCLUSION: The combination of 2DE-3DE for ARVC diagnosis is comparable to the conventional 2DE-cMRI approach. 3DE should be performed in all suspected ARVC patients to aide in the detection of WMA.

Cardiac Masses and Pseudomasses: An Overview about Diagnostic Imaging and Clinical Background.

A cardiac lesion detected at ultrasonography might turn out to be a normal structure, a benign tumor or rarely a malignancy, and lesion characterization is very important to appropriately manage the lesion itself. The exact relationship of the mass with coronary arteries and the knowledge of possible concomitant coronary artery disease are necessary preoperative information. Moreover, the increasingly performed coronary CT angiography to evaluate non-invasively coronary artery disease leads to a rising number of incidental findings. Therefore, CT and MRI are frequently performed imaging modalities when echocardiography is deemed insufficient to evaluate a lesion. A brief comprehensive overview about diagnostic radiological imaging and the clinical background of cardiac masses and pseudomasses is reported.

Hypoallergenic unicompartmental knee arthroplasty and return to sport: comparison between Oxidized Zirconium and Titanium Niobium Nitride.

BACKGROUND: The present study aims to compare the rate of return to sports in patients who underwent surgery for mobile-bearing UKA with either hypoallergenic TiNbN or with oxidized zirconium alloy implants. METHODS: The records of two consecutive cohorts for a total of 90 hypoallergenic implants were prospectively analysed. The first cohort consisted of 41 consecutive series of medial mobile-bearing hypoallergenic TiNbN UKA, whereas the second cohort consisted of 49 consecutive medial fixed-bearing hypoallergenic Uni Oxinium.The clinical evaluation involved evaluating each patient's University of California, Los Angeles (UCLA) activity scoresand the High-Activity Arthroplasty Score(HAAS). Each patient was clinically evaluated on the day before surgery (T0), then after a minimum follow-up period of 12 months (T1), and finally after 24 months (T2).   Results:The only pre-operative difference between the two groups involved pre-operative BMI with significantly higher BMI in TiNbN Group (p<0.001). Both groups reported significant improvement at each follow-up compared with the previous and also at the final follow up with respect to UCLA and HAAS (p<0.05), except for UCLA in TiNbN between T1 and T2(p>0.05). Moreover, BMI improved significantly at the final follow up, but only in TiNbN group (p<0.05). CONCLUSIONS: Both TiNbN and Oxinium UKA procedures enabled patients to return to an acceptable level of sports activity with excellent radiographic outcomes after the final follow up regardless of the age, gender, BMI, and bearing type.

The Influence of Baseline Clinical Status and Surgical Strategy on Early Good to Excellent Result in Spinal Lumbar Arthrodesis: A Machine Learning Approach.

The study aims to create a preoperative model from baseline demographic and health-related quality of life scores (HRQOL) to predict a good to excellent early clinical outcome using a machine learning (ML) approach. A single spine surgery center retrospective review of prospectively collected data from January 2016 to December 2020 from the institutional registry (SpineREG) was performed. The inclusion criteria were age ≥ 18 years, both sexes, lumbar arthrodesis procedure, a complete follow up assessment (Oswestry Disability Index-ODI, SF-36 and COMI back) and the capability to read and understand the Italian language. A delta of improvement of the ODI higher than 12.7/100 was considered a "good early outcome". A combined target model of ODI (Δ ≥ 12.7/100), SF-36 PCS (Δ ≥ 6/100) and COMI back (Δ ≥ 2.2/10) was considered an "excellent early outcome". The performance of the ML models was evaluated in terms of sensitivity, i.e., True Positive Rate (TPR), specificity, i.e., True Negative Rate (TNR), accuracy and area under the receiver operating characteristic curve (AUC ROC). A total of 1243 patients were included in this study. The model for predicting ODI at 6 months' follow up showed a good balance between sensitivity (74.3%) and specificity (79.4%), while providing a good accuracy (75.8%) with ROC AUC = 0.842. The combined target model showed a sensitivity of 74.2% and specificity of 71.8%, with an accuracy of 72.8%, and an ROC AUC = 0.808. The results of our study suggest that a machine learning approach showed high performance in predicting early good to excellent clinical results.

Tumoral Phenocopies of Hypertrophic Cardiomyopathy: The Role of Cardiac Magnetic Resonance.

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease that presents with cardiac hypertrophy. HCM phenocopies are clinical conditions that are phenotypically undistinguishable from HCM, but with a different underlying etiology. Cardiac tumors are rare entities that can sometimes mimic HCM in their echocardiographic appearance, thus representing an example of HCM phenocopy. At present, only case reports of tumoral HCM phenocopies can be found in literature. In this systematic review, we analyzed all the published cases in which a cardiac tumor mimicked HCM to the point of misleading the diagnosis, providing a structured overview of the currently available evidence on this topic.

Sacubitril/Valsartan to Treat Heart Failure in a Patient with Relapsing Hairy Cell Leukaemia: Case Report.

Experience with angiotensin-receptor neprilysin inhibitors (ARNI) in oncologic patients with heart failure (HF) is limited. We report a case of ARNI started as first-choice therapy in a patient with relapsing hairy cell leukaemia (HCL) and HF with depressed left ventricular ejection fraction (LVEF). A middle-aged male, previously treated with rituximab for HCL, was scheduled for cardiologic screening before starting a new antineoplastic therapy for cancer relapse. The patient had symptomatic HF with reduced LVEF and high NT-proBNP levels. In this patient, early ARNI treatment was well tolerated and produced a rapid and durable improvement of symptoms, LVEF and NT-proBNP levels. Consequently, the oncologic team could start an experimental treatment with obinutuzumab, with complete HCL remission. In conclusion, in this patient with HCL and HF, ARNI therapy was safe and effective, contributing to undelayed cancer treatment.

Cardiovascular magnetic resonance assessment of biventricular changes during vacuum bell correction of pectus excavatum.

BACKGROUND: Evidence of cardiac dysfunction in patients with pectus excavatum (PE) remains controversial. A growing number of studies report increased exercise tolerance following surgery. Nevertheless, many consider the correction of PE a cosmetic intervention, with post-operative changes ascribed to the concurrent growth of the young patient population. No studies have investigated non-invasively the immediate cardiac changes following relief of the deformity. The aim of this study was to assess cardiac function before and during temporary sternal elevation using the non-invasive vacuum bell (VB) device on young adults with PE. METHODS: Adult patients scheduled for surgical correction of PE underwent cardiac magnetic resonance imaging (CMRI) before and during the application of the VB. Steady-state free precession sequences were used for the evaluation of biventricular volume and function. Phase contrast sequences measured the aortic and pulmonary flow to calculate stroke index (SI). Scans were analyzed post hoc by the same investigator. A control group of healthy individuals was assessed in the same way. RESULTS: In total, 20 patients with PE (mean age 23±10 years) and 10 healthy individuals (mean age 25±6 years) underwent CMR before and during VB application. Before intervention, baseline cardiac volumes and function were similar between the groups, with patient-values in the low-to-normal range. Following VB application, PE patients revealed a 10% increase in biventricular SI. Furthermore, left ventricular end-diastolic volume index (LV EDVI) improved by 8% and right ventricular ejection fraction (RV EF) increased by 7%. These findings were not mirrored in the healthy individuals. No correlations were found between improved cardiac parameters and the baseline Haller index (HI) of PE patients. CONCLUSIONS: Non-invasive, momentary correction of PE is associated with an immediate improvement in SI, RV EF and LV EDVI, not observed in controls. The findings suggest that sternal depression in PE patients affects cardiac function.

Clinical recommendations of cardiac magnetic resonance, Part II: inflammatory and congenital heart disease, cardiomyopathies and cardiac tumors: a position paper of the working group 'Applicazioni della Risonanza Magnetica' of the Italian Society of Cardiology.

The current document was developed by the working group on the 'application of cardiac magnetic resonance' of the Italian Society of Cardiology to provide a perspective on the current state of technical advances and clinical cardiac magnetic resonance applications and to inform cardiologists how to implement their clinical and diagnostic pathway with the introduction of this technique in the clinical practice. Appropriateness criteria were defined using a score system: score 1-3 = inappropriate (test is not generally acceptable and is not a reasonable approach for the indication), score 4-6 = uncertain (test may be generally acceptable and may be a reasonable approach for the indication but more research and/or patient information is needed to classify the indication definitively) and score 7-9 = appropriate (test is generally acceptable and is a reasonable approach for the indication).

Modeling Staphylococcus epidermidis-Induced Non-Unions: Subclinical and Clinical Evidence in Rats.

S. epidermidis is one of the leading causes of orthopaedic infections associated with biofilm formation on implant devices. Open fractures are at risk of S. epidermidis transcutaneous contamination leading to higher non-union development compared to closed fractures. Although the role of infection in delaying fracture healing is well recognized, no in vivo models investigated the impact of subclinical low-grade infections on bone repair and non-union. We hypothesized that the non-union rate is directly related to the load of this commonly retrieved pathogen and that a low-grade contamination delays the fracture healing without clinically detectable infection. Rat femurs were osteotomized and stabilized with plates. Fractures were infected with a characterized clinical-derived methicillin-resistant S. epidermidis (10(3), 10(5), 10(8) colony forming units) and compared to uninfected controls. After 56 days, bone healing and osteomyelitis were clinically assessed and further evaluated by micro-CT, microbiological and histological analyses. The biofilm formation was visualized by scanning electron microscopy. The control group showed no signs of infection and a complete bone healing. The 10(3) group displayed variable response to infection with a 67% of altered bone healing and positive bacterial cultures, despite no clinical signs of infection present. The 10(5) and 10(8) groups showed severe signs of osteomyelitis and a non-union rate of 83-100%, respectively. The cortical bone reaction related to the periosteal elevation in the control group and the metal scattering detected by micro-CT represented limitations of this study. Our model showed that an intra-operative low-grade S. epidermidis contamination might prevent the bone healing, even in the absence of infectious signs. Our findings also pointed out a dose-dependent effect between the S. epidermidis inoculum and non-union rate. This pilot study identifies a relevant preclinical model to assess the role of subclinical infections in orthopaedic and trauma surgery and to test specifically designed diagnostic, prevention and therapeutic strategies.

Does a thrombin-based topical haemostatic agent reduce blood loss and transfusion requirements after total knee revision surgery? A randomized, controlled trial.

PURPOSE: The aim of the present study was to assess the efficacy of a thrombin-based topical haemostatic in reducing blood requirements after total knee replacement (TKR) revision surgery. METHODS: This prospective, randomized, controlled study was designed to evaluate the haemostatic efficacy and safety of a thrombin-based topical haemostatic (Floseal) versus standard treatment in patients receiving total knee revision arthroplasty. The decrease in haemoglobin values postsurgery and the blood units transfused were recorded. The decision to transfuse was made by a surgeon blinded to the patient's group allocation. RESULTS: Forty-eight patients were enroled in the study; twenty-four patients each were randomized to the treatment and control groups, respectively. The median decrease in haemoglobin concentration on the first postoperative day was 2.2 g/dL in the treatment group and 2.7 g/dL in the control group. A significant reduction in units of blood transfused was also observed in the treatment group compared with the control group [1.1 ± 1.13 (range 0-4) vs. 1.9 ± 1.41 (range 0-5) blood units; P = 0.04]. No major treatment-related adverse events were recorded in the study. CONCLUSIONS: This study shows that a thrombin-based topical haemostatic reduces the need for blood transfusion in TKR revision surgery. CLINICAL RELEVANCE: A thrombin-based topical haemostatic agent can be an appropriate solution to enhance haemostasis and vessel sealing at the operative site in TKR revision surgery, in order to reduce the need for blood transfusion after surgery. LEVEL OF EVIDENCE: II.

Diabetic mouse model of orthopaedic implant-related Staphylococcus aureus infection.

BACKGROUND: Periprosthetic bacterial infections represent one of the most challenging orthopaedic complications that often require implant removal and surgical debridement and carry high social and economical costs. Diabetes is one of the most relevant risk factors of implant-related infection and its clinical occurrence is growing worldwide. The aim of the present study was to test a model of implant-related infection in the diabetic mouse, with a view to allow further investigation on the relative efficacy of prevention and treatment options in diabetic and non-diabetic individuals. METHODOLOGY: A cohort of diabetic NOD/ShiLtJ mice was compared with non-diabetic CD1 mice as an in vivo model of S. aureus orthopaedic infection of bone and soft tissues after femur intramedullary pin implantation. We tested control and infected groups with 1×10(3) colony-forming units of S. aureus ATCC 25923 strain injected in the implant site. At 4 weeks post-inoculation, host response to infection, microbial biofilm formation, and bone damage were assessed by traditional diagnostic parameters (bacterial culture, C-reactive protein and white blood cell count), histological analysis and imaging techniques (micro computed tomography and scanning electron microscopy). RESULTS: Unlike the controls and the CD1 mice, all the diabetic mice challenged with a single inoculum of S. aureus displayed severe osteomyelitic changes around the implant. CONCLUSIONS: Our findings demonstrate for the first time that the diabetic mouse can be successfully used in a model of orthopaedic implant-related infection. Furthermore, the same bacteria inoculum induced periprosthetic infection in all the diabetic mice but not in the controls. This animal model of implant-related infection in diabetes may be a useful tool to test in vivo treatments in diabetic and non-diabetic individuals.

Cardiac and acoustic metastases in relapsing melanoma.

Herein we report the case of a 45-year-old woman with known history of malignant melanoma, complaining recent onset of bilateral hearing problems initially addressed to acoustic neuroma. Dedicated (18)F-FDG PET/CT and MR imaging documented the presence of 3 areas of pathologic uptake in the V-VII-VIII cranial nerves, other 2 in the neck and in the medullary sheath, and another unexpected lesion in the interventricular septum. All lesions showed intense (18)F-FDG uptake, high precontrast T1-weighted signal, contrast enhancement in T1-weighted sequences with gadolinium, and hypervascularization/high signal in T2-weighted images: these features were considered in keeping with diffused malignant melanoma metastatization.