Diagnostic accuracy of fully hybrid [68Ga]Ga-PSMA-11 PET/MRI and [68Ga]Ga-RM2 PET/MRI in patients with biochemically recurrent prostate cancer: a prospective single-center phase II clinical trial.

PURPOSE: To compare the diagnostic accuracy and detection rates of PET/MRI with [68Ga]Ga-PSMA-11 and [68Ga]Ga-M2 in patients with biochemical recurrence of prostate cancer (PCa). METHODS: Sixty patients were enrolled in this prospective single-center phase II clinical trial from June 2020 to October 2022. Forty-four/60 completed all study examinations and were available at follow-up (median: 22.8 months, range: 6-31.5 months). Two nuclear medicine physicians analyzed PET images and two radiologists interpreted MRI; images were then re-examined to produce an integrated PET/MRI report for both [68Ga]Ga-PSMA-11 and [68Ga]Ga-RM2 examinations. A composite reference standard including histological specimens, response to treatment, and conventional imaging gathered during follow-up was used to validate imaging findings. Detection rates, accuracy, sensitivity, specificity, positive, and negative predictive value were assessed. McNemar's test was used to compare sensitivity and specificity on a per-patient base and detection rate on a per-region base. Prostate bed, locoregional lymph nodes, non-skeletal distant metastases, and bone metastases were considered. p-value significance was defined below the 0.05 level after correction for multiple testing. RESULTS: Patients' median age was 69.8 years (interquartile range (IQR): 61.8-75.1) and median PSA level at time of imaging was 0.53 ng/mL (IQR: 0.33-2.04). During follow-up, evidence of recurrence was observed in 31/44 patients. Combining MRI with [68Ga]Ga-PSMA-11 PET and [68Ga]Ga-RM2 PET resulted in sensitivity = 100% and 93.5% and specificity of 69.2% and 69.2%, respectively. When considering the individual imaging modalities, [68Ga]Ga-RM2 PET showed lower sensitivity compared to [68Ga]Ga-PSMA-11 PET and MRI (61.3% vs 83.9% and 87.1%, p = 0.046 and 0.043, respectively), while specificity was comparable among the imaging modalities (100% vs 84.6% and 69.2%, p = 0.479 and 0.134, respectively). CONCLUSION: This study brings further evidence on the utility of fully hybrid PET/MRI for disease characterization in patients with biochemically recurrent PCa. Imaging with [68Ga]Ga-PSMA-11 PET showed high sensitivity, while the utility of [68Ga]Ga-RM2 PET in absence of a simultaneous whole-body/multiparametric MRI remains to be determined.

Valve-in-valve transcatheter aortic valve implantation: The issues behind crossing a bioprosthesis.

Valve-in-valve transcatheter aortic valve implantation (ViV TAVI) is rapidly arising as a safe and effective alternative to redo-surgery in the treatment of bioprostheses deterioration. While scientific community is currently focusing its attention on the most common limitations related to this procedure, such as the risk of coronary obstruction and patient-prosthesis mismatch, data regarding the first step of a ViV TAVI, the crossing of a degenerated bioprosthesis, are still lacking. The aim of this review is to analyze the available information about bioprosthesis crossing, to show the inherent challenges encountered by interventional cardiologists during valve crossing and to describe the current strategies to perform a correct crossing.

Clinical profiling and outcomes of viral myocarditis manifesting with ventricular arrhythmias.

Aims: Clinical features and risk stratification of patients with viral myocarditis (VM) complicated by ventricular arrhythmias (VA) are incompletely understood. We aim to describe arrhythmia patterns and outcomes in patients with VM and early-onset VA. Methods and results: We present a single-centre study, enrolling patients with VM proven by endomyocardial biopsy, and evidence of VA within 24 h of hospitalization. The incidence of major adverse events (MAE), including all-cause death, severe heart failure, advanced atrioventricular blocks, or major VA, was evaluated during a 24-month follow-up (FU) and compared with a matched group of virus-negative myocarditis. Of patients with VM (n = 74, mean age 47 ± 16 years, 66% males, and left ventricular ejection fraction 51 ± 13%), 20 (27%) presented with major VA [ventricular tachycardia/ventricular fibrillation (VT/VF)], and 32 (44%) had polymorphic VA. Patients with polymorphic VA more commonly had evidence of ongoing systemic infection (24/32 vs. 10/42, P = 0.004) and experienced greater occurrence of MAE at discharge (15/32 vs. 2/42, P < 0.001). However, the incidence of MAE during FU was higher in patients with monomorphic VA compared to those with polymorphic VA (17/42 vs. 2/28, P = 0.002). Patients with monomorphic VA displayed frequently signs of chronic cardiomyopathy and had outcomes comparable with virus-negative myocarditis (log rank P = 0.929). Presentation with VT/VF was independently associated with MAE [at discharge: hazard ratio (HR) 4.7, 95% confidence interval (CI) 1.6-14.0, P = 0.005; during FU: HR 6.3, 95% CI 2.3-17.6, P < 0.001]. Conclusion: In patients with VM, polymorphic VA point to ongoing systemic infection and early adverse outcomes, whereas monomorphic VA suggest chronic cardiomyopathy and greater incidence of MAE during FU. Presentation with VT/VF is independently associated with MAE.

Multimodal Detection and Targeting of Biopsy-Proven Myocardial Inflammation in Genetic Cardiomyopathies: A Pilot Report.

The authors present a clinical report focused on the overlap between myocarditis and genetic cardiomyopathies of the dilated and arrhythmogenic spectrum. Our cohort was composed of 25 patients undergoing extensive baseline characterization and prospective reassessment by a dedicated multidisciplinary disease unit during a median follow-up of 69 months. We showed that the use of multimodal imaging allowed both discrimination of specific genotypes and identification of myocardial inflammation proven using endomyocardial biopsy. In addition, we showed that the use of immunomodulatory therapy was beneficial for most patients.

The impact of mitral valve surgery on ventricular arrhythmias in patients with Barlow's disease: preliminary results of a prospective study.

OBJECTIVES: Aim of this study was to evaluate arrhythmic burden of patients with Barlow's disease and significant mitral regurgitation (MR) and assess the impact of mitral repair on ventricular arrhythmias (VA) in this group of subjects. METHODS: We prospectively included 88 consecutive patients with Barlow's disease referred to our Institution from February 2021 to May 2022. All enrolled patients underwent 24-h Holter monitoring before surgery. Sixty-three of them completed 3 months echocardiographic and Holter follow-up. Significant arrhythmic burden was defined as ≥1% premature ventricular beats/24 h or at least one episode of non-sustained ventricular tachycardia (VT), VT or ventricular fibrillation. RESULTS: At baseline, 29 patients (33%) were arrhythmogenic (AR), while 59 (67%) were not [non-arrhythmogenic (NAR)]. AR subjects tended to be more often females with history of palpitations. Sixty-three patients completed 3-months follow-up. Twenty of them (31.7%) were AR at baseline and 43 (68.3%) were not. Among AR patients, 9 (45%) remained AR after mitral surgery, while 11 (55%) became NAR. Considering NAR subjects at baseline, after mitral valve repair 8 (18.6%) evolved into AR, while 35 (81.4%) remained NAR. A higher prevalence of pre-operative MAD was found among patients experiencing VA reduction if compared with patients who remained arrhythmogenic (63.6% vs 11.1%, P = 0.028). CONCLUSIONS: In our experience, one-third of Barlow's patients referred for mitral surgery showed a significant arrhythmic burden. Almost half of the subjects arrhythmogenic at baseline were free from significant VA after mitral repair. However, a minority (18.6%) of subjects without arrhythmic burden at baseline experienced significant VA at follow-up.

Cardiovascular involvement in Erdheim-Chester diseases is associated with myocardial fibrosis and atrial dysfunction.

PURPOSE: Erdheim-Chester disease (ECD) is a rare multisystem histiocytosis, whose cardiovascular involvement has not been systematically characterized so far. We aimed to systematically (qualitatively and quantitatively) describe the features of cardiovascular involvement in a large cohort of ECD patients and to evaluate its impact on myocardial fibrosis extension and cardiac function. MATERIAL AND METHODS: Among 54 patients with biopsy-proven ECD, 29 patients (59 ± 12 years, 79% males) underwent 1.5-T CMR using a standardized protocol for qualitative and quantitative assessment of disease localization, evaluation of atrial and ventricular function, and assessment of non-dense and dense myocardial fibrosis. RESULTS: The right atrioventricular (AV) groove was the most commonly affected cardiac site (76%) followed by the right atrial walls (63%), thoracic aorta (59%), and superior vena cava (38%). Right AV groove involvement, encasing the right ventricular artery, was associated with non-dense myocardial fibrosis in the infero-septal (20/26 patients) and the inferior (14/26 patients) mid-basal left ventricular (LV) wall. In two patients with right AV groove localization, LGE revealed myocardial infarction in the same myocardial segments. Three out of five patients with left AV groove involvement had non-dense LGE on the lateral LV mid-basal wall. Bulky right atrial pseudomass was associated with atrial dysfunction and superior and inferior vena cava stenosis. CONCLUSIONS: In ECD patients, AV groove localization is associated with LV wall fibrosis in the downstream coronary territories, suggesting hemodynamic alterations due to coronary encasement. Conversely, atrial pseudomass ECD localizations impact on atrial contractility causing atrial dysfunction and are associated with atrio-caval junction stenosis.

Feasibility and reliability of comprehensive three-dimensional transoesophageal echocardiography screening process for transcatheter mitral valve replacement.

AIMS: The procedural planning of transcatheter mitral valve replacement (TMVR) requires a specific imaging assessment to establish patient eligibility. Computed tomography (CT) is considered the reference method. In this setting, data regarding the role of transoesophageal echocardiography (TOE) are lacking. We evaluated the feasibility and reliability of a comprehensive 3D-TOE screening in TMVR candidates. METHODS AND RESULTS: We performed a retrospective observational study including 72 consecutive patients who underwent a pre-procedural CT and 3D-TOE for TMVR evaluation. The measurements of mitral annulus (MA), length of anterior mitral leaflet (AML), native left ventricular outflow tract (LVOT), and predicted neo-LVOT acquired with CT and 3D-TOE were compared using a novel semi-automated software for post processing analysis (3 mensio Structural Heart 10.1-3mSH, Pie Medical Imaging, Bilthoven, Netherlands). The final suitability decision was given by the valve manufacturer based on CT measurements and clinical conditions. Among 72 patients screened, all patients had adequate image quality for 3D-TOE analysis. 3D-TOE and CT measurements for AML length (r = 0.97), MA area (r = 0.90), perimeter (r = 0.68), anteroposterior (r = 0.88), and posteromedial-anterolateral (r = 0.74) diameters were found highly correlated, as well as for native LVOT (r = 0.86) and predicted neo-LVOT areas (r = 0.96) (all P-values <0.0001). An almost perfect agreement between CT and 3DTOE was found in assessing the eligibility for TMVR implantation (Cohen kappa 0.83, P < 0.001). CONCLUSION: 3D-TOE appraisements showed good correlations with CT measurements and high accuracy to predict TMVR screening success.

Cardiac magnetic resonance abnormalities in patients with acute myocarditis proven by septal endomyocardial biopsy.

BACKGROUND: Previous studies suggest low diagnostic sensitivity of cardiac magnetic resonance (CMR) imaging based on Lake Louise criteria (LLC) to identify patients with complicated presentations of acute myocarditis (AM). We evaluated classic and updated LLC in patients with AM proven by right ventricular septal endomyocardial biopsy (RVS-EMB). METHODS: From an initial population of 499 patients with clinically suspected AM from a multicenter retrospective cohort, we included 74 patients with histologically proven myocarditis on RVS-EMB and available CMR within 30 days since admission. The prevalence of total and septal CMR abnormalities [namely, T2-weighted images (T2W), late gadolinium enhancement (LGE), T2 and T1 mapping, and extracellular volume (ECV)] were assessed in patients with complicated vs. uncomplicated AM. RESULTS: Among 74 patients [mean age 38 ± 15 years, 65% males, left ventricular ejection fraction (LVEF) 40 ± 18%] with RVS-EMB-proven AM, 53 (72%) had a complicated presentation. The classic LLC were positive in 56/74 patients (76%), whereas the updated ones were positive in 41/41 of cases (100%). Septal involvement, documented in 48/74 patients (65%) by conventional T2W/LGE and in 39/41 cases (95%) by mapping techniques (p < 0.001), was more common in patients with complicated AM. In the 41 patients undergoing both evaluations, CMR sensitivity for myocarditis was 85% for the classic LLC vs. 100% for the updated LLC (p = 0.006). CONCLUSION: In patients with myocarditis on RVS-EMB, CMR using updated LLC has high sensitivity in the detection of AM when performed within 30 days. Septal abnormalities are more common in patients with complicated AM.

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.

Clinical Applications of FDG-PET Scan in Arrhythmic Myocarditis.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan has no recognized role in diagnosis, prognosis, and disease monitoring in patients with arrhythmic myocarditis. OBJECTIVES: The purpose of this study was to investigate the value of FDG-PET scan in arrhythmic myocarditis. METHODS: The authors enrolled 75 consecutive patients (age 47 ± 14 years, 65% men) undergoing FDG-PET scan for arrhythmic myocarditis. Myocarditis was diagnosed by endomyocardial biopsy (EMB) and, whenever applicable, cardiac magnetic resonance (CMR). RESULTS: Indications for FDG-PET scan included either contraindication to CMR (n = 50) or mismatch between CMR and EMB (n = 25). Overall, 50 patients (67%) had positive FDG-PET. Sensitivity was 75% referring to EMB, and 73% to CMR. Specificity was 67% referring to EMB, and 59% to CMR. FDG-PET accuracy was lower in the presence of borderline myocarditis, and either late (>30 days) or on-immunosuppression FDG-PET scanning. Anteroseptal distribution pattern, found in 12 of 50 (24%) patients including 7 of 7 cardiac sarcoidosis cases, was associated with greater occurrence of ventricular arrhythmias and atrioventricular blocks in 4.2 ± 1.7 years of follow-up (10 of 12 vs 7 of 38, and 7 of 12 vs 0 of 38, respectively; both P < 0.001). In 39 patients (52%), FDG-PET was repeated by 13 ± 2 months, allowing immunosuppression withdrawal after FDG uptake normalization either by first (76%) or second reassessment (24%). CONCLUSIONS: FDG-PET scan may be a clinically useful diagnostic technique in arrhythmic myocarditis, in particular when CMR is unsuitable because of irregular heartbeat or implantable cardioverter-defibrillator-related artifacts. Anteroseptal FDG distribution is associated with a worse arrhythmic outcome and should raise the suspicion of cardiac sarcoidosis. During follow-up, repeated FDG-PET allows myocarditis monitoring to guide immunosuppression withdrawal.

Exercise Stress Test Late after Arrhythmic versus Nonarrhythmic Presentation of Myocarditis.

Background. Exercise stress test (EST) has been scarcely investigated in patients with arrhythmic myocarditis. Objectives. To report the results of EST late after myocarditis with arrhythmic vs. nonarrhythmic presentation. Methods. We enrolled consecutive adult patients with EST performed at least six months after acute myocarditis was diagnosed using gold-standard techniques. Patients with ventricular arrhythmia (VA) at presentation were compared with the nonarrhythmic group. Adverse events occurring during follow-up after EST included cardiac death, disease-related rehospitalization, malignant VA, and proven active myocarditis. Results. The study cohort was composed of 128 patients (age 41 ± 9 y, 70% males) undergoing EST after myocarditis. Of them, 64 (50%) had arrhythmic presentation. EST was performed after 15 ± 4 months from initial diagnosis, and was conducted on betablockers in 75 cases (59%). During EST, VA were more common in the arrhythmic group (43 vs. 4, p < 0.001), whereas signs and symptoms of ischemia were more prevalent in the nonarrhythmic one (6 vs. 1, p = 0.115). By 58-month mean follow-up, 52 patients (41%) experienced adverse events, with a greater prevalence among arrhythmic patients (39 vs. 13, p < 0.001). As documented both in the arrhythmic and nonarrhythmic subgroups, patients had greater prevalence of adverse events following a positive EST (40/54 vs. 12/74 with negative EST, p < 0.001). Electrocardiographic features of VA during EST correlated with the subsequent inflammatory restaging of myocarditis. Nonarrhythmic patients with uneventful EST both on- and off-treatment were free from subsequent adverse events. Conclusions. Late after the arrhythmic presentation of myocarditis, EST was frequently associated with recurrent VA. In both arrhythmic and nonarrhythmic myocarditis, EST abnormalities correlated with subsequent adverse outcomes.

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.

Radiomic and gEnomic approaches for the enhanced DIagnosis of clear cell REnal Cancer (REDIRECt): a translational pilot methodological study.

Background: The combination of radiomic and transcriptomic approaches for patients diagnosed with small clear-cell renal cell carcinoma (ccRCC) might improve decision making. In this pilot and methodological study, we investigate whether imaging features obtained from computed tomography (CT) may correlate with gene expression patterns in ccRCC patients. Methods: Samples from 6 patients who underwent partial nephrectomy for unilateral non-metastatic ccRCC were included in this pilot cohort. Transcriptomic analysis was conducted through RNA-sequencing on tumor samples, while radiologic features were obtained from pre-operative 4-phase contrast-enhanced CT. To evaluate the heterogeneity of the transcriptome, after a 1,000 re-sampling via bootstrapping, a first Principal Component Analyses (PCA) were fitted with all transcripts and a second ones with transcripts deriving from a list of 369 genes known to be associated with ccRCC from The Cancer Genome Atlas (TCGA). Significant pathways in each Principal Components for the 50 genes with the highest loadings absolute values were assessed with pathways enrichment analysis. In addition, Pearson's correlation coefficients among radiomic features themselves and between radiomic features and transcripts expression values were computed. Results: The transcriptomes of the analysed samples showed a high grade of heterogeneity. However, we found four radiogenomic patterns, in which the correlation between radiomic features and transcripts were statistically significant. Conclusions: We showed that radiogenomic approach is feasible, however its clinical meaning should be further investigated.

Use of an antagonist of HMGB1 in mice affected by malignant mesothelioma: a preliminary ultrasound and optical imaging study.

BACKGROUND: Malignant mesothelioma (MM) is an aggressive tumor, with a poor prognosis, usually unresectable due to late diagnosis, mainly treated with chemotherapy. BoxA, a truncated form of "high mobility group box 1" (HMGB1), acting as an HMGB1 antagonist, might exert a defensive action against MM. We investigated the potential of BoxA for MM treatment using experimental 40-MHz ultrasound and optical imaging (OI) in a murine model. METHODS: Murine MM cells infected with a lentiviral vector expressing the luciferase gene were injected into the peritoneum of 14 BALB/c mice (7 × 104 AB1-B/c-LUC cells). These mice were randomized to treatment with BoxA (n = 7) or phosphate-buffered saline (controls, n = 7). The experiment was repeated with 40 mice divided into two groups (n = 20 + 20) and treated as above to confirm the result and achieve greater statistical power. Tumor presence was investigated by experimental ultrasound and OI; suspected peritoneal masses underwent histopathology and immunohistochemistry examination. RESULTS: In the first experiment, none of the 7 controls survived beyond day 27, whereas 4/7 BoxA-treated mice (57.1%) survived up to day 70. In the second experiment, 6/20 controls (30.0%) and 16/20 BoxA-treated mice (80.0%) were still alive at day 34 (p = 0.004). In both experiments, histology confirmed the malignant nature of masses detected using experimental ultrasound and OI. CONCLUSION: In our preclinical experience on a murine model, BoxA seems to exert a protective role toward MM. Both experimental ultrasound and OI proved to be reliable techniques for detecting MM peritoneal masses.

68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI in Recurrent Prostate Cancer: Diagnostic Performance and Association with Clinical and Histopathological Data.

The aim of the present study is to investigate and compare the performances of 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI in identifying recurrent prostate cancer (PCa) after primary treatment and to explore the association of dual-tracer PET findings with clinical and histopathological characteristics. Thirty-five patients with biochemical relapse (BCR) of PCa underwent 68Ga PSMA PET/MRI for restaging purpose, with 31/35 also undergoing 68Ga-DOTA-RM2 PET/MRI scan within 16 days (mean: 3 days, range: 2-16 days). Qualitative and quantitative image analysis has been performed by comparing 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI findings both on a patient and lesion basis. Clinical and instrumental follow-up was used to validate PET findings. Fisher's exact test and Mann-Whitney U test were used to investigate the association between dual-tracer PET findings, clinical and histopathological data. p-value significance was defined below the 0.05 level. Patients' mean age was 70 years (range: 49-84) and mean PSA at time of PET/MR scans was 1.88 ng/mL (range: 0.21-14.4). A higher detection rate was observed for 68Ga-PSMA PET/MRI, with more lesions being detected compared to 68Ga-DOTA-RM2 PET/MRI (26/35 patients, 95 lesions vs. 15/31 patients, 41 lesions; p = 0.016 and 0.002). 68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI findings were discordant in 11/31 patients; among these, 10 were 68Ga-PSMA positive (9/10 confirmed as true positive and 1/10 as false positive by follow-up examination). Patients with higher levels of PSA and shorter PSA doubling time (DT) presented more lesions on 68Ga-PSMA PET/MRI (p = 0.006 and 0.044), while no association was found between PET findings and Gleason score. 68Ga-PSMA has a higher detection rate than 68Ga-DOTA-RM2 in detecting PCa recurrence. The number of 68Ga-PSMA PET positive lesions is associated with higher levels of PSA and shorter PSA DT, thus representing potential prognostic factors.

Myocardial Late Contrast Enhancement CT in Troponin-Positive Acute Chest Pain Syndrome.

Background Acute chest pain with mild troponin rise and inconclusive diagnosis after clinical evaluation represents a diagnostic challenge. Triple-rule-out (TRO) CT may exclude coronary artery disease (CAD), as well as acute aortic syndrome and pulmonary embolism, but cannot help identify other causes of myocardial injury. Purpose To investigate the diagnostic value of a comprehensive CT protocol including both an angiographic and a late contrast enhancement (LCE) scan in participants with troponin-positive acute chest pain. Materials and Methods In this prospective study, consecutive patients with troponin-positive acute chest pain or anginal equivalent and inconclusive diagnosis after clinical evaluation (symptoms, markers, electrocardiography, and echocardiography) who underwent TRO CT between June 2018 and September 2020 were enrolled. TRO CT was performed to evaluate the presence of obstructive CAD (stenosis ≥50%), acute aortic syndrome, and pulmonary embolism. If the findings on the TRO CT scan were negative, an LCE CT scan was acquired after 10 minutes to assess the presence and pattern of scar and quantify the myocardial extracellular volume fraction. CT-based diagnoses were compared with diagnoses obtained with reference standard methods, including invasive coronary angiography, cardiac MRI, and endomyocardial biopsy. Results Eighty-four patients (median age, 69 years [interquartile range, 50-77 years]; 45 men) were enrolled. TRO CT helped identify obstructive CAD in 35 participants (42%), acute aortic syndrome in one (1.2%), and pulmonary embolism in six (7.1%). LCE CT scans were acquired in the remaining 42 participants. The following diagnoses were reached with use of LCE CT: myocarditis (22 of 42 participants [52%]), takotsubo cardiomyopathy (four of 42 [10%]), amyloidosis (three of 42 [7.1%]), myocardial infarction with nonobstructed coronary arteries (three of 42 [7.1%]), dilated cardiomyopathy (two of 42 [4.8%]), and negative or inconclusive findings (eight of 42 [19%]). The addition of LCE CT improved the diagnostic rate of TRO CT from 42 of 84 participants (50% [95% CI: 38.9, 61.1]) to 76 of 84 (90% [95% CI: 82.1, 95.8]) (P < .001). Conclusion A CT protocol including triple-rule-out and late contrast enhancement CT scans improved diagnostic rate in participants presenting with acute chest pain syndrome. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Nagpal and Bluemke in this issue.

Physical activity volume in patients with arrhythmogenic cardiomyopathy is associated with recurrence after ventricular tachycardia ablation.

PURPOSE: To assess the role of intense physical activity (PA) on recurrence after ventricular tachycardia (VT) ablation in arrhythmogenic cardiomyopathy (ACM). METHODS: We retrospectively analyzed 63 patients with definite diagnosis of ACM who underwent to catheter ablation (CA) of VT. PA was quantified in METs per week by IPAQ questionnaire in 51 patients. VT-free survival time after ablation was analyzed by Kaplan-Meier's curves. RESULTS: The weekly amount of PA was higher in patients with VT recurrence (2303.1 METs vs 1043.5 METs, p = 0.042). The best cutoff to predict VT recurrence after CA was 584 METs/week (AUC = 0.66, sensibility = 85.0%, specificity = 45.2%). Based on this cutoff, 34 patients were defined as high level athletes (Hi-PA) and 17 patients as low-level athletes (Lo-PA). During a median follow-up of 32.0 months (11.5-65.5), 22 patients (34.9%) experienced VT recurrence. Lo-PA patients had a longer VT-free survival, compared with Hi-PA patients (82.4% vs 50.0%, log-rank p = 0.025). At Cox multivariate analysis, independent predictors of the VT recurrence were PA ≥ 584 METs/week (Hi-PA) (HR = 2.61, CI 95% 1.03-6.58, p = 0.04) and late potential (LP) abolition (HR = 0.38, CI 95% 0.16-0.89, p = 0.03). CONCLUSIONS: PA ≥ 584 METs/week and LP abolition were independent predictors of VT recurrence after ablation.

Characterization of the electrophysiological substrate in patients with Barlow's disease.

BACKGROUND: Myxomatous mitral valve prolapse (MVP) and mitral-annular disjunction (Barlow disease) are at-risk for ventricular arrhythmias (VA). Fibrosis involving the papillary muscles and/or the infero-basal left ventricular (LV) wall was reported at autopsy in sudden cardiac death (SCD) patients with MVP. OBJECTIVES: We investigated the electrophysiological substrate subtending VA in MVP patients with Barlow disease phenotype. METHODS: Twenty-three patients with VA were enrolled, including five with syncope and four with a history of SCD. Unipolar (Uni < 8.3 mV) and bipolar (Bi < 1.5 mV) low-voltage areas were analyzed with electro-anatomical mapping (EAM), and VA inducibility was evaluated with programmed ventricular stimulation (PES). Electrophysiological parameters were correlated with VA patterns, electrocardiogram (ECG) inferior negative T wave (nTW), and late gadolinium enhancement (LGE) assessed by cardiac magnetic resonance. RESULTS: Premature ventricular complex (PVC) burden was 12 061.9 ± 12 994.6/24 h with a papillary-muscle type (PM-PVC) in 18 patients (68%). Twelve-lead ECG showed nTW in 12 patients (43.5%). A large Uni less than 8.3 mV area (62.4 ± 45.5 cm2 ) was detected in the basal infero-lateral LV region in 12 (73%) patients, and in the papillary muscles (2.2 ± 2.9 cm2 ) in 5 (30%) of 15 patients undergoing EAM. A concomitant Bi less than 1.5 mV area (5.0 ± 1.0 cm2 ) was identified in two patients. A history of SCD, and the presence of nTW, and LGE were associated with a greater Uni less than 8.3 mV extension: (32.8 ± 3.1 cm2 vs. 9.2 ± 8.7 cm2 ), nTW (20.1 ± 11.0 vs. 4.1 ± 3.8 cm2 ), and LGE (19.2 ± 11.7 cm2 vs. 1.0 ± 2.0 cm2 , p = .013), respectively. All patients with PM-PVC had a Uni less than 8.3 mV area. Sustained VA (ventricular tachycardia 2 and VF 2) were induced by PES only in four patients (one with resuscitated SCD). CONCLUSIONS: Low unipolar low voltage areas can be identified with EAM in the basal inferolateral LV region and in the papillary muscles as a potential electrophysiological substrate for VA and SCD in patients with MVP and Barlow disease phenotype.

Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis.

The microbiota comprises the microorganisms that live in close contact with the host, with mutual benefit for both counterparts. The contribution of the gut microbiota to the emergence of castration-resistant prostate cancer (CRPC) has not yet been addressed. We found that androgen deprivation in mice and humans promotes the expansion of defined commensal microbiota that contributes to the onset of castration resistance in mice. Specifically, the intestinal microbial community in mice and patients with CRPC was enriched for species capable of converting androgen precursors into active androgens. Ablation of the gut microbiota by antibiotic therapy delayed the emergence of castration resistance even in immunodeficient mice. Fecal microbiota transplantation (FMT) from CRPC mice and patients rendered mice harboring prostate cancer resistant to castration. In contrast, tumor growth was controlled by FMT from hormone-sensitive prostate cancer patients and Prevotella stercorea administration. These results reveal that the commensal gut microbiota contributes to endocrine resistance in CRPC by providing an alternative source of androgens.

Tocilizumab for the treatment of immune-related adverse events: a systematic literature review and a multicentre case series.

OBJECTIVE: Research is moving towards a more personalized management of immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI). Our objective was to evaluate the efficacy and safety of tocilizumab in the treatment of these clinical manifestations. METHODS: A systematic literature review was performed to retrieve data about the use of tocilizumab in the treatment of irAEs. Additionally, data from cancer patients referred to our Immune-related Adverse Event Clinic and treated with tocilizumab were collected. RESULTS: Our literature review identified 20 articles and 11 meeting abstracts. Data about 91 cancer patients who received tocilizumab for the treatment of irAEs were collected. In 85% of cases, this therapy was associated with clinical benefit and no case of disease progression was reported. ICI therapy was continued following irAE onset and biologic therapy initiation in only three patients. Five patients developed irAEs upon ICI initiation and were subsequently treated with tocilizumab at our Centre. At a median follow-up of eight months, tocilizumab was safely continued along with ICI in three out of five patients, and an adequate control of irAE was obtained in all cases. No significant adverse reactions to tocilizumab were reported. Only one patient experienced a disease progression 18 months after ICI discontinuation. CONCLUSION: Both our systematic literature review and case series highlight the efficacy and safety of tocilizumab in the treatment of irAEs. Furthermore, they both support the possibility of a combined approach with tocilizumab and ICI, to guarantee an effective irAEs management without losing the oncologic response.