Role of Cardiovascular Magnetic Resonance in Cardiac Amyloidosis: A Narrative Review.

Amyloidosis is a rare infiltrative condition resulting from the extracellular accumulation of amyloid fibrils at the cardiac level. It can be an acquired condition or due to genetic mutations. With the progression of imaging technologies, a non-invasive diagnosis was proposed. In this study, we discuss the role of CMR in cardiac amyloidosis, focusing on the two most common subtypes (AL and ATTR), waiting for evidence-based guidelines to be published.

An Explainable Radiogenomic Framework to Predict Mutational Status of KRAS and EGFR in Lung Adenocarcinoma Patients.

The complex pathobiology of lung cancer, and its spread worldwide, has prompted research studies that combine radiomic and genomic approaches. Indeed, the early identification of genetic alterations and driver mutations affecting the tumor is fundamental for correctly formulating the prognosis and therapeutic response. In this work, we propose a radiogenomic workflow to detect the presence of KRAS and EGFR mutations using radiomic features extracted from computed tomography images of patients affected by lung adenocarcinoma. To this aim, we investigated several feature selection algorithms to identify the most significant and uncorrelated sets of radiomic features and different classification models to reveal the mutational status. Then, we employed the SHAP (SHapley Additive exPlanations) technique to increase the understanding of the contribution given by specific radiomic features to the identification of the investigated mutations. Two cohorts of patients with lung adenocarcinoma were used for the study. The first one, obtained from the Cancer Imaging Archive (TCIA), consisted of 60 cases (25% EGFR, 23% KRAS); the second one, provided by the Azienda Ospedaliero-Universitaria 'Ospedali Riuniti' of Foggia, was composed of 55 cases (16% EGFR, 28% KRAS). The best-performing models proposed in our study achieved an AUC of 0.69 and 0.82 on the validation set for predicting the mutational status of EGFR and KRAS, respectively. The Multi-layer Perceptron model emerged as the top-performing model for both oncogenes, in some cases outperforming the state of the art. This study showed that radiomic features can be associated with EGFR and KRAS mutational status in patients with lung adenocarcinoma.

Recent Non-Invasive Parameters to Identify Subjects at High Risk of Sudden Cardiac Death.

Cardiovascular diseases remain among the leading causes of death worldwide and sudden cardiac death (SCD) accounts for ~25% of these deaths. Despite its epidemiologic relevance, there are very few diagnostic strategies available useful to prevent SCD mainly focused on patients already affected by specific cardiovascular diseases. Unfortunately, most of these parameters exhibit poor positive predictive accuracy. Moreover, there is also a need to identify parameters to stratify the risk of SCD among otherwise healthy subjects. This review aims to provide an update on the most relevant non-invasive diagnostic features to identify patients at higher risk of developing malignant ventricular arrhythmias and SCD.

Incidence of cardiovascular events in patients with chronic myeloid leukaemia treated with tyrosine kinase inhibitors.

BACKGROUND: The introduction of imatinib and tyrosine kinase inhibitors as therapeutic strategy for Philadelphia chromosome-positive chronic myeloid leukaemia (CML) has represented an important step forward for treatment of this disease. The aim of this study was therefore to evaluate the incidence of cardiovascular adverse events (CVEs) in patients affected by CML treated with TKI in an observational prospective study. METHODS: All consecutive patients affected by CML and treated with TKI in our Institution were enrolled in the study from February 2005 to September 2018 with a clinical, laboratory and instrumental follow-up. RESULTS: Sixty-one consecutive patients were enrolled, 29 with imatinib, 15 with nilotinib, 11 with dasatinib, 3 with bosutinib and 3 with ponatinib. Neither patients in therapy with bosutinib nor with nilotinib had CVE during follow-up. Incidence rates per person/year were 0 for bosutinib and nilotinib, 0.15 for dasatinib, 0.19 for imatinib and 1.69 for ponatinib (Log Rank p < 0.05); differences in terms of incidence of adverse outcomes remained significant also after multivariate correction. CONCLUSIONS: In patients with CML treated with TKIs, therapy with ponatinib was associated with a higher risk of CVE than other TKIs. The lowest incidence of CVE was associated with bosutinib and nilotinib.

Rapamycin Inhibitors for Eye Squamous Cell Carcinoma after Renal Transplantation: A Case Report.

INTRODUCTION: The immunosuppressive efficiency obtained in the last decades in kidney transplantation significantly improved graft survival. However, there is still a high risk and incidence of cancer in transplant patients strongly and directly related to the type of immunosuppression. An increasing body of evidence suggests that the PI3K/Akt/mTOR pathway may play a pivotal role in the development and progression of several neoplastic diseases. CASE PRESENTATION: We describe a 47-year-old male patient who received a cadaveric primary renal transplant in November 2008 developing a poorly differentiated infiltrating and ulcerated squamous cell carcinoma (SCC) at the eye level. In this patient, the modification of an immunosuppressive regimen with introduction of rapamycin (mTOR) inhibitors and withdrawal of calcineurin inhibitors (CNIs) led to the resolution of this severe condition. CONCLUSION: The introduction of mTOR inhibitors and withdrawal of CNIs in kidney-transplanted patients with de novo eye SCC should be considered in this clinical setting.

Concealed structural heart disease discovered at cardiac magnetic resonance in patients with ventricular extrasystoles from ventricular outflow tract and apparently normal hearts.

BACKGROUND: Outflow tract (OT) premature ventricular contractions (PVCs) are commonly found in clinical practice; in most cases, PVCs are benign and observed in structurally normal hearts, not requiring any therapeutic intervention. In this study, we therefore sought to evaluate with cardiac magnetic resonance (CMR) patients with PVC and apparently normal heart at echocardiographic examination, in order to identify possible substrates linked with higher prevalence of arrhythmias or structural heart disease. METHODS: Thirty-three consecutive patients with frequent PVCs originating from the ventricular OT (right and left) were enrolled in the study and assessed by echocardiography and CMR. All patients had normal baseline electrocardiogram. RESULTS: CMR showed structural changes in 5 patients out of 33; in 3 cases, areas of fibrosis limited in one case to the middle basal segments of the interventricular septum and in two patients to the middle basal segments of the inferior-lateral wall were found. In 2 other cases, however, late gadolinium enhancement showed significant anomalies characterized in one patient by extensive areas of subepicardial fibrosis of the left ventricle, suitable with arrhythmogenic left dominant dysplasia; in another patient, a marked trabeculation of left ventricular medium apical segments suitable with non-compaction myocardium was present. CONCLUSIONS: CMR may identify cases of structural heart disease in subjects with OT PVCs and apparently normal electrocardiogram and echocardiogram examinations. A preliminary screening with CMR may be considered before any further invasive electrophysiology assessment and therapeutic planning.

Mini invasive approaches in the treatment of small renal masses: TC-guided renal cryoablation in elderly.

BACKGROUND: Today, the goal of surgery is to achieve oncological efficacy with the lowest complication rate. Computed Tomography (CT)-guided cryoablation is proposed as a safe and effective technique. We report, our series of small renal masses treated with cryoablation in elderly (> 70 years). METHODS: From May 2014 to April 2019, 32 patients with median (IQR) age of 75.5 years (range 71-80) with small renal masses (< T1a) diagnosis, clinical anesthesia contraindications to nephron-sparing surgery or patient's will previous informed consent have been selected at our Urology Department. All patients underwent CT-guided cryoablation, preceded by needle biopsy. The cryoablation consisted in a procedure with an argon/helium gas-based system under local anesthesia. The follow-up included CT abdomen at 3, 6 and 12 months. The definition of incomplete treatment was the persistence of the lesion contrast enhancement (CE) at the end of the scan; the definition of relapse was the appearance of the CE to the 6-month control CT. RESULTS: The median follow-up was 30 months (IQR 1-59). The median size of the tumor was 3.85 cm (IQR 1.6-4.5). All patients underwent lesion biopsy resulting in diagnosis of Renal Cell Carcinoma (RCC) in 29 patients (90.7%) and oncocytoma in 3 patients (9.3%). A median of 2 cryoprobes (IQR 1- 3) was used and 2/3 cycles of freeze-thaw of the duration of 10 minutes or 5 minutes were performed. Complications were: 3 asymptomatic transitional perirenal effusion, 2 lumbar pain well-controlled by analgesic drug. Hospital stay was 2 days (range 1-3). No case showed incomplete treatment and local relapse or metastates at the CT abdomen-pelvis with contrast medium at 12 months. CONCLUSIONS: This study shows the efficacy and safety of percutaneous cryoablation of small renal masses in elderly population. The procedure is easy to perform, with low complication rates and well tolerated by the elderly patients.

Cardiac Tumors.

Cardiac tumors (CTs) are extremely rare, with an incidence of approximately 0.02% in autopsy series. Primary tumors of the heart are far less common than metastatic tumors. CTs usually present with any possible clinical combination of heart failure, arrhythmias, or embolism. Echocardiography remains the first diagnostic approach when suspecting a CT which, on the other side, frequently appears unexpectedly during an echocardiographic examination. Yet, cardiac tomography and especially magnetic resonance imaging may offer several adjunctive opportunities in the diagnosis of CTs. Early and exact diagnosis is crucial for the following therapy and outcome of CTs.

Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by neoplastic transformation of pluripotent cells due to a typical cytogenetic and molecular mutation known as Philadelphia (Ph) chromosome. In 2001, the introduction of the tyrosine kinasis inhibitor (TKI) imatinib as a therapeutic strategy for CML with PH chromosome mutation represented an important step towards treatment of these patients, and nowadays, this drug represents the gold therapeutic standard in this clinical setting. A second generation of TKIs (dasatinib, nilotinib, and bosutinib) showed an effective action in all patients with mutations resistant to imatinib. Ponatinib is a third-generation TKI and is the only inhibitor with activity against T3151 mutation. The impact of ponatinib on cardiovascular events was first evaluated in the PACE trial. We therefore report and discuss most relevant evidence currently available on cardiovascular events associated with the use of ponatinib. Though many exams can be used for diagnosis and follow-up of this kind of cardiotoxicity, echocardiography seems to have a pivotal role thanks to its feasibility, availability, and low cost.

Anomalous Right Coronary Artery Origin from Left Main Stem: Role of Cardio-Computed Tomography in the Diagnosis and Therapeutic Approach.

Anomalous coronary arteries (ACAs) are rare but potentially life-threatening abnormalities of coronary circulation. Most of the variants are benign; however, some may lead to myocardial ischemia and/or sudden cardiac arrest. We report the case of a 75-year-old male complaining of exertion chest discomfort. Admission electrocardiogram on presentation showed sinus bradycardia with a slight elevation of ST-T in inferior leads. Troponin levels, however, were normal. Coronary angiography showed an anomalous right coronary artery (RCA) originating from the left main stem without significant stenosis. Cardio-CT confirmed the anomalous origin of the RCA from the left main stem and showed its anomalous course between the aorta and the pulmonary artery. The patient was deemed a candidate for surgery and transferred to a cardiac surgery center. Only the exact definition of the anatomic and clinical features of ACAs may allow the identification of the most appropriate and effective treatment. Multislice computed tomography may play a fundamental role in the diagnosis and treatment of ACAs.

Parachute mitral valve assessed by cardiac magnetic resonance.

Parachute mitral valve (PMV) is a congenital cardiac malformation where typically all tendons chordae converge and insert into one major papillary muscle. We report the case of 27-year-old man affected by Hodgkin's lymphoma-mixed cellularity subtype with polychemotherapy treatment and Barrett's esophagus who came to our attention for routine echocardiographic exam and evaluation of left ventricular function. In the presence of normal left ventricular systolic function and mild-moderate mitral regurgitation, a careful examination of mitral apparatus showed a single papillary muscle suspected for PMV. In the presence of Barrett's esophagus, the patient was further assessed cardiac magnetic resonance (CMR) that confirmed the diagnosis of PMV and excluded other associated congenital anomalies. Despite the rare incidence of PMV and a diagnosis generally based on transesophageal echocardiography, CMR could represent a useful tool, in selected cases, to confirm the diagnosis of PMV, identify other possible congenital anomalies, and assess ventricular and valvular function.

Mitral annular calcification: Can CMR be useful in identifying caseous necrosis?

Mitral annular calcification (MAC) can resemble an intracardiac mass and it is defined as a chronic degeneration of the mitral annulus. Often reported is caseous mitral annulus calcification (CMAC), a periannular, extensive calcification resembling a tumor. We report the case of a 68-year-old woman who had been hospitalized for palpitations and dyspnea. The transthoracic and transesophageal echocardiography revealed a non-homogeneous, slightly mobile, round mass, attached to the ventricular side of posterior mitral leaflet, with central echo-lucent area and without acoustic shadowing. Therefore, a cardiac magnetic resonance (CMR) was performed; delayed enhancement sequences showed a non-enhanced central core surrounded by a hyperenhanced rim (fibrous cap). To confirm the diagnosis, a multidetector computed tomography (MDCT) was performed; the MDCT showed a hyperdense mass with a hypodense center and a calcified peripheral rim. The central content had heterogeneous fluid density without significant contrast enhancement. The MDCT findings were considered highly suggestive of CMAC. CMR may be useful for the identification and definition of pericardial and myocardial masses and CMAC.

Don't stop at first glance: pulmonary artery angiosarcoma mimicking chronic thromboembolic pulmonary hypertension.

We report the case of an incomplete diagnosis of chronic thromboembolic pulmonary hypertension, with relevant prognostic implications, missing the presence of a primary pulmonary artery angiosarcoma. After the late neoplasm diagnosis, the patient, treated for months with riociguat, was considered inoperable and died soon after. This case highlights the need to manage patients with suspected pulmonary arterial hypertension by expert referral centers with specific and multi-professional expertise (heart and thoracic imaging) in order to avoid incomplete or delayed diagnoses.

Tricuspid Papillary Fibroelastoma at Multimodal Imaging.

Papillary fibroelastoma is a rare benign cardiac tumor, second after cardiac myxoma as more frequent cardiac valvular tumor. The therapy is usually based on surgery according to size, mobility, symptoms, and risks of surgery. We report the case of a 67-year old female with transient ischemic attack. Echocardiography showed the presence of a round mobile formation localized on the atrial side of septal leaflets of tricuspid valve, first identified as an endocarditis vegetation. Cardiac magnetic resonance (cMRI) confirmed the presence of the mass and showed an isointense signal in T1-turbo spin echo sequences, hypointense in cine steady-state free precession and in first-pass sequences, and hyperintense in T2 and phase-sensitive inversion recovery with central hypointense core, with a suspected diagnosis of fibroelastoma. The patient underwent cardiac surgery and histology confirmed the presence of fibroelastic tissue with papillary extroflexions compatible with diagnosis of fibroelastoma. The use of cMRI may be useful in the evaluation of the exact position, dimensions, and nature of cardiac masses and fibroelastomas, diagnostic workup, and preliminary assessment before surgery.