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Background: The limited ability of enzyme replacement therapy (ERT) in removing globotriaosylceramide from cardiomyocytes is recognized for advanced Fabry disease cardiomyopathy (FDCM). Prehypertrophic FDCM is believed to be cured or stabilized by ERT. However, no pathologic confirmation is available. We report here on the long-term clinical-pathologic impact of ERT on prehypertrophic FDCM., Methods and Results: Fifteen patients with Fabry disease with left ventricular maximal wall thickness ≤10.5 mm at cardiac magnetic resonance required endomyocardial biopsy because of angina and ventricular arrhythmias. Endomyocardial biopsy showed coronary small-vessel disease in the angina cohort, and vacuoles in smooth muscle cells and cardiomyocytes ≈20% of the cell surface containing myelin bodies at electron microscopy. Patients received α-agalsidase in 8 cases, and β-agalsidase in 7 cases. Both groups experienced symptom improvement except 1 patients treated with α-agalsidase and 1 treated with β-agalsidase. After ERT administration ranging from 4 to 20 years, all patients had control cardiac magnetic resonance and left ventricular endomyocardial biopsy because of persistence of symptoms or patient inquiry on disease resolution. In 13 asymptomatic patients with FDCM, left ventricular maximal wall thickness and left ventricular mass, cardiomyocyte diameter, vacuole surface/cell surface ratio, and vessels remained unchanged or minimally increased (left ventricular mass increased by <2%) even after 20 years of observation, and storage material was still present at electron microscopy. In 2 symptomatic patients, FDCM progressed, with larger and more engulfed by globotriaosylceramide myocytes being associated with myocardial virus-negative lymphocytic inflammation., Conclusions: ERT stabilizes storage deposits and myocyte dimensions in 87% of patients with prehypertrophic FDCM. Globotriaosylceramide is never completely removed even after long-term treatment. Immune-mediated myocardial inflammation can overlap, limiting ERT activity.

Cardiac computed tomography angiography (CCTA) is considered the standard non-invasive tool to rule-out obstructive coronary artery disease (CAD). Moreover, several imaging biomarkers have been developed on cardiac-CT imaging to assess global CAD severity and atherosclerotic burden, including coronary calcium scoring, the segment involvement score, segment stenosis score and the Leaman-score. Myocardial perfusion imaging enables the diagnosis of myocardial ischemia and microvascular damage, and the CT-based fractional flow reserve quantification allows to evaluate non-invasively hemodynamic impact of the coronary stenosis. The texture and density of the epicardial and perivascular adipose tissue, the hypodense plaque burden, the radiomic phenotyping of coronary plaques or the fat radiomic profile are novel CT imaging features emerging as biomarkers of inflammation and plaque instability, which may implement the risk stratification strategies. The ability to perform myocardial tissue characterization by extracellular volume fraction and radiomic features appears promising in predicting arrhythmogenic risk and cardiovascular events. New imaging biomarkers are expanding the potential of cardiac CT for phenotyping the individual profile of CAD involvement and opening new frontiers for the practice of more personalized medicine., (© 2024. The Author(s).)

Background: We investigated the differences in impairment of left ventricle (LV) and left atrium (LA) contractile dysfunction between subacute and convalescent takotsubo syndrome (TTS), using myocardial strain analysis by cardiac magnetic resonance (CMR) feature-tracking technique., Methods: We retrospectively selected 50 patients with TTS clinical-radiological diagnosis who underwent CMR within 30 days since symptoms onset: 19 studied during the early subacute phase (sTTS, ≤ 7 days) and 31 during the convalescence (cTTS, 8-30 days). We measured the following: LV global longitudinal, circumferential, and radial strain (lvGLS, lvGCS, lvGRS) and strain rate (SR) and LA reservoir (laS&#95;r), conduit (laS&#95;cd), and booster pump strain (laS&#95;bp) and strain rate (laSR&#95;r, laSR&#95;cd, laSR&#95;bp). Patients were compared with 30 age- and sex-matched controls., Results: All patients were women (mean age 63 years). TTS patients showed altered LV- and LA-strain features, compared to controls. sTTS was associated with increased laS&#95;bp (12.7% versus 9.8%) and reduced lvEF (47.4% versus 54.8%), lvGLS (-12.2% versus 14.6%), and laS&#95;cd (7.0% versus 9.5%) compared to cTTS (p ≤ 0.029). The interval between symptoms onset and CMR was correlated with laS&#95;bp (r = -0.49) and lvGLS (r = 0.47) (p = 0.001 for both). At receiver operating characteristics analysis, laS&#95;bp was the best discriminator between sTTS and cTTS (area under the curve [AUC] 0.815), followed by lvGLS (AUC 0.670)., Conclusions: LA dysfunction persists during the subacute and convalescence of TTS. laS&#95;bp increases in subacute phase with progressive decrease during convalescence, representing a compensatory mechanism of LV dysfunction and thus a useful index of functional recovery., Relevance Statement: Atrial strain has the potential to enhance the delineation of cardiac injury and functional impairment in TTS patients, assisting in the identification of individuals at higher risk and facilitating the implementation of more targeted and personalized medical therapies., Key Points: • In TTS, after ventricular recovery, atrial dysfunction persists assessable with CMR feature tracking. • Quantitative assessment of atrial strain discriminates atrial functions: reservoir, conduit, and booster pump. • Atrial booster pump changes after acute TTS, regardless of ventricular function. • Atrial strain may serve as a temporal marker in TTS., (© 2024. The Author(s).)

We aimed to comprehensively analyze by three-dimensional speckle-tracking echocardiography (3DSTE) and Doppler echocardiography right ventricular (RV) performance, pulmonary arterial (PA) elastic properties and right ventricular-pulmonary artery coupling (RVPAC) in patients with repaired tetralogy of Fallot (rTOF) and assess the feasibility and clinical utility of related echocardiographic indices. Twenty-four adult patients with rTOF and twenty-four controls were studied. RV end-diastolic volume(3D-RVEDV), RV end-systolic volume(3D-RVESV), RV ejection fraction(3D-RVEF), RV longitudinal strain(3D-RVLS) and RV area strain(3D-RVAS) were calculated by 3DSTE. RV end-systolic area (RVESA) was obtained by planimetry. Pulmonary regurgitation (PR) was assessed as trivial/mild or significant by cardiac magnetic resonance (CMR) and color-Doppler. Pulmonary artery (PA) elastic properties were determined using two-dimensional/Doppler echocardiography. RV systolic pressure (RVSP) was measured using standard Doppler methods. RVPAC was assessed using various 3DSTE-derived parameters (3DRVAS/RVSP, 3DRVLS/RVESA, 3DRVAS/RVESV). Overall, 3DRVEF and 3DRVAS were impaired in rTOF patients compared with controls. PA pulsatility and capacitance were reduced (p = 0.003) and PA elastance was higher (p = 0.0007) compared to controls. PA elastance had a positive correlation with 3DRVEDV (r = 0.64, p = 0.002) and 3DRVAS (r = 0.51, p = 0.02). By ROC (receiver operating characteristics) analysis, 3DRVAS/RVESV, 3DRVAS/RVSP and 3DRVLS/RVESA cutoff values of 0.31%/mmHg, 0.57%/mmHg and 0.86%/mmHg, respectively, had 91%, 88% and 88% sensitivity and 81%, 81% and 79% specificity in identifying exercise capacity impairment. In rTOF patients increased 3DSTE-derived RV volumes and impaired RV ejection fraction and strain are associated with reduced PA pulsatility and capacitance and increased PA elastance. 3DSTE-derived RVPAC parameters using different afterload-markers are accurate indices of exercise capacity., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: To evaluate the impact of vaccination on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moreover on coronavirus disease 2019 (COVID-19) pneumonia, by assessing the extent of lung disease using the CT severity score (CTSS)., Methods: Between September 2021 and February 2022, SARS-CoV-2 positive patients who underwent chest CT were retrospectively enrolled. Anamnestic and clinical data, including vaccination status, were obtained. All CT scans were evaluated by two readers using the CTSS, based on a 25-point scale. Univariate and multivariate logistic regression analyses were performed to evaluate the associations between CTSS and clinical or demographic variables. An outcome analysis was used to differentiate clinical outcome between vaccinated and unvaccinated patients., Results: Of the 1040 patients (537 males, 503 females; median age 58 years), 678 (65.2%) were vaccinated and 362 (34.8%) unvaccinated. Vaccinated patients showed significantly lower CTSS compared to unvaccinated patients (p < 0.001), also when patients without lung involvement (CTSS = 0) were excluded (p < 0.001). Older age, male gender and lower number of doses administered were associated with higher CTSS, however, in the multivariate analysis, vaccination status resulted to be the variable with the strongest association with CTSS. Clinical outcomes were significantly worse in unvaccinated patients, including higher number of ICU admissions and higher mortality rates., Conclusions: Lung involvement during COVID-19 was significantly less severe in vaccinated patients compared with unvaccinated patients, who also showed worse clinical outcomes. Vaccination status was the strongest variable associated to the severity of COVID-related, more than age, gender, and number of doses administered., (© 2023. The Author(s).)

Purpose: One of the major challenges in the management of familial hypercholesterolemia (FH) is the stratification of cardiovascular risk in asymptomatic subjects. Our purpose is to investigate the performance of clinical scoring systems, Montreal-FH-score (MFHS), SAFEHEART risk (SAFEHEART-RE) and FH risk score (FHRS) equations and Dutch Lipid Clinic Network (DLCN) diagnostic score, in predicting extent and severity of CAD at coronary computed tomography angiography (CCTA) in asymptomatic FH., Material and Methods: One-hundred and thirty-nine asymptomatic FH subjects were prospectively enrolled to perform CCTA. MFHS, FHRS, SAFEHEART-RE and DLCN were assessed for each patient. Atherosclerotic burden scores at CCTA (Agatston score [AS], segment stenosis score [SSS]) and CAD-RADS score were calculated and compared to clinical indices., Results: Non-obstructive CAD was found in 109 patients, while 30 patients had a CAD-RADS ≥ 3. Classifying the two groups according to AS, values varied significantly for MFHS (p < 0.001), FHRS (p < 0.001) and SAFEHEART-RE (p = 0.047), while according to SSS only MFHS and FHRS showed significant differences (p < 0.001). MFHS, FHRS and SAFEHEART-RE, but not DLCN, showed significant differences between the two CAD-RADS groups (p < .001). MFHS proved to have the best discriminatory power (AUC = 0.819; 0.703-0.937, p < 0.001) at ROC analysis, followed by FHRS (AUC = 0.795; 0.715-0.875, p < .0001) and SAFEHEART-RE (AUC = .725; .61-.843, p < .001)., Conclusions: Greater values of MFHS, FHRS and SAFEHEART-RE are associated to higher risk of obstructive CAD and might help to select asymptomatic patients that should be referred to CCTA for secondary prevention., (© 2023. The Author(s).)

Papillary muscle (PPM) involvement in myocardial infarction (MI) increases the risk of secondary mitral valve regurgitation or PPM rupture and may be diagnosed using late gadolinium enhancement (LGE) imaging. The native T1-mapping (nT1) technique and PPM longitudinal strain (PPM-ls) have been used to identify PPM infarction (iPPM) without the use of the contrast agent. This study aimed to assess the diagnostic performance of nT1 and PPM-ls in the identification of iPPM. Forty-six patients, who performed CMR within 14-30 days after MI, were retrospectively enrolled: sixteen showed signs of iPPM on LGE images. nT1 values were measured within the infarcted area (IA), remote myocardium (RM), blood pool (BP), and anterolateral and posteromedial PPMs and compared using ANOVA. PPM-ls values have been assessed on cineMR images as the percentage of shortening between end-diastolic and end-systolic phases. Higher nT1 values and lower PPM-ls were found in infarcted compared to non-infarcted PPMs (nT1: 1219.3 ± 102.5 ms vs. 1052.2 ± 80.5 ms and 17.6 ± 6.3% vs. 21.6 ± 4.3%; p -value < 0.001 for both), with no significant differences between the nT1 of infarcted PPMs and IA and between the non-infarcted PPMs and RM. ROC analysis demonstrated an excellent discriminatory power for nT1 in detecting the iPPM (AUC = 0.874; 95% CI: 0.784-0.963; p < 0.001). nT1 and PPM-ls are valid tools in assessing iPPM with the advantage of avoiding contrast media administration.

Purpose: To propose a sustainable model of coronary computed tomography angiography (CCTA) use in acute coronary syndrome (ACS) in emergency department (ED) using a partially based teleradiology reporting model. We also analyzed impact of the protocol on short- and long-term patient's outcome., Methods: During a 12-month period, 104 consecutive patients admitted to the ED for acute chest pain (ACP) with low-to-intermediate risk of ACS were selected and underwent CCTA. Medical reporting was based on a model combining on-site physician and a remote radiologist supported by a web client-based teleradiology system, covering a 24/7 service. CCTA findings were correlated with the incidence of major adverse cardiovascular events (MACEs) over a 5-year follow-up., Results: CCTA ruled-out CAD in 76 patients (73.1%). Moderate (7.7%) to severe (19.2%) CAD was identified in 28 patients who were directly referred to functional tests or invasive angiography. The mean discharge time was 10.8 ± 5.8 h; patients with absent to mild disease were safely and quickly discharged. Remote reporting using a teleradiology platform was performed in 82/104 cases (78.9%), with slight impact on patient's discharge time (10.4 ± 5.6 vs. 12.1 ± 6.1 h, p: 0.24). MACEs at 6-month and at 5-year follow-up were 0.96% (n = 1/104) and 15.5% (n = 14/90)., Conclusion: CCTA assessment of patients with ACP enables to quickly rule-out ACS, avoiding waste of time and resources, to identify patients with obstructive CAD which should be referred to subsequent tests and to stratify the risk of MACEs at short and long time. A partial teleradiology based 24/7 CCTA service is feasible and sustainable, even in small ED., (Copyright © 2022 Elsevier B.V. All rights reserved.)

To assess the impact of regurgitant jet direction on left ventricular function and intraventricular hemodynamics in asymptomatic patients with bicuspid aortic valve (BAV) and mild aortic valve regurgitation (AR), using cardiac magnetic resonance (CMR) feature tracking and 4D flow imaging. Fifty BAV individuals were retrospectively selected: 15 with mild AR and posterior regurgitation jet (Group-PJ), 15 with regurgitant jet in other directions (Group-nPJ) and 20 with no regurgitation (Controls). CMR protocol included cine steady state free precession (SSFP) sequences and 4D Flow imaging covering the entire left ventricle (LV) cavity and the aortic root. Cine-SSFP images were analyzed to assess LV volumes, longitudinal and circumferential myocardial strain. Circumferential and longitudinal peak diastolic strain rate (PDSR) and peak diastolic velocity (PDV) were reduced in group PJ if compared to group nPJ and control group (PDSR = 1.10 ± 0.2 1/s vs. 1.34 ± 0.5 1/s vs. 1.53 ± 0.3 1/s, p:0.001 and 0.68 ± 0.2 1/s vs. 1.17 ± 0.2 1/s vs. 1.05 ± 0.4 1/s ; p < 0.001, PDV = - 101.6 ± 28.1 deg/s vs. - 201.4 ± 85.9 deg/s vs. - 221.6 ± 67.1 deg/s; p < 0.001 and - 28.1 ± 8 mm/s vs. - 38.9 ± 11.1 mm/s vs. - 43.6 ± 14.3 mm/s, p < 0.001, respectively), whereas no differences have been found in systolic strain values. 4D Flow images (available only in 9 patients) showed deformation of diastolic transmitral streamlines direction in group PJ compared to other groups. In BAV patients with mild AR, the posterior direction of the regurgitant jet may hamper the complete mitral valve opening, disturbing transmitral flow and slowing the LV diastolic filling., (© 2021. The Author(s).)

Purpose: The aim of the study was to prospectively evaluate the agreement between chest magnetic resonance imaging (MRI) and computed tomography (CT) and to assess the diagnostic performance of chest MRI relative to that of CT during the follow-up of patients recovered from coronavirus disease 2019., Materials and Methods: Fifty-two patients underwent both follow-up chest CT and MRI scans, evaluated for ground-glass opacities (GGOs), consolidation, interlobular septal thickening, fibrosis, pleural indentation, vessel enlargement, bronchiolar ectasia, and changes compared to prior CT scans. DWI/ADC was evaluated for signal abnormalities suspicious for inflammation. Agreement between CT and MRI was assessed with Cohen's k and weighted k. Measures of diagnostic accuracy of MRI were calculated., Results: The agreement between CT and MRI was almost perfect for consolidation (k = 1.00) and change from prior CT (k = 0.857); substantial for predominant pattern (k = 0.764) and interlobular septal thickening (k = 0.734); and poor for GGOs (k = 0.339), fibrosis (k = 0.224), pleural indentation (k = 0.231), and vessel enlargement (k = 0.339). Meanwhile, the sensitivity of MRI was high for GGOs (1.00), interlobular septal thickening (1.00), and consolidation (1.00) but poor for fibrotic changes (0.18), pleural indentation (0.23), and vessel enlargement (0.50) and the specificity was overall high. DWI was positive in 46.0% of cases., Conclusions: The agreement between MRI and CT was overall good. MRI was very sensitive for GGOs, consolidation and interlobular septal thickening and overall specific for most findings. DWI could be a reputable imaging biomarker of inflammatory activity., (© 2021. The Author(s).)

An 82-year-old woman with precordial pain at rest was admitted to the Emergency Department for possible cardiac heart disease; electrocardiogram excluded ischemia and high-sensitive troponin was normal. Echocardiogram revealed a hyperechoic mass adjacent to the mitral annulus. Electrocardiography-gated computed tomography (CT) angiography exam confirmed the presence of the mass protruding into the atrioventricular groove, adjacent to the posterior mitral. On the precontrast images the lesion was hyperdense with some scattered central calcific spots. CT findings are typical of a giant caseous calcification of the mitral annulus and excluded the diagnoses of pseudoaneurysm (it does not show any communication with the left ventricular cavity), neoplasm/abscess (complete caseous/calcified content) or infected/abscessified mitral calcification (absence of internal hypodense core). This is a benign condition that can be easily misdiagnosed as ventricular aneurysm or pseudoaneurysm on the contrast-enhanced images, when the caseous content is isodense to the iodinated blood pool., (© 2021 The Authors. Journal of Cardiac Surgery published by Wiley Periodicals LLC.)

We proposed a combined cardiothoracic-MRI (CaTh-MRI) protocol for the comprehensive assessment of cardiovascular structures, lung parenchyma, and pulmonary arterial tree, in COVID-19 patients with progressive worsening of clinical conditions and/or suspicion of acute-onset myocardial inflammation. A 25-minutes fast protocol was also conceived for unstable or uncooperative patients by restricting the number of sequences to those necessary to rule out myocardial and to assess pulmonary involvement. In patients requiring CMR characterization of myocardial damage, the addition of lung and thoracic vessel evaluation is of clinical benefit at a minimal time expense., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Early detection of myocardial involvement can be relevant in coronavirus disease 2019 (COVID-19) patients to timely target symptomatic treatment and decrease the occurrence of the cardiac sequelae of the infection. The aim of the present study was to assess the clinical value of cardiovascular magnetic resonance (CMR) in characterizing myocardial damage in active COVID-19 patients, through the correlation between qualitative and quantitative imaging biomarkers with clinical and laboratory evidence of myocardial injury., Methods: In this retrospective observational cohort study, we enrolled 27 patients with diagnosis of active COVID-19 and suspected cardiac involvement, referred to our institution for CMR between March 2020 and January 2021. Clinical and laboratory characteristics, including high sensitivity troponin T (hs-cTnT), and CMR imaging data were obtained. Relationships between CMR parameters, clinical and laboratory findings were explored. Comparisons were made with age-, sex- and risk factor-matched control group of 27 individuals, including healthy controls and patients without other signs or history of myocardial disease, who underwent CMR examination between January 2020 and January 2021., Results: The median (IQR) time interval between COVID-19 diagnosis and CMR examination was 20 (13.5-31.5) days. Hs-cTnT values were collected within 24 h prior to CMR and resulted abnormally increased in 18 patients (66.6%). A total of 20 cases (74%) presented tissue signal abnormalities, including increased myocardial native T1 (n = 11), myocardial T2 (n = 14) and extracellular volume fraction (ECV) (n = 10), late gadolinium enhancement (LGE) (n = 12) or pericardial enhancement (n = 2). A CMR diagnosis of myocarditis was established in 9 (33.3%), pericarditis in 2 (7.4%) and myocardial infarction with non-obstructive coronary arteries in 3 (11.11%) patients. T2 mapping values showed a moderate positive linear correlation with Hs-cTnT (r = 0.58; p = 0.002). A high degree positive linear correlation between ECV and Hs-cTnT was also found (r 0.77; p < 0.001)., Conclusions: CMR allows in vivo recognition and characterization of myocardial damage in a cohort of selected COVID-19 individuals by means of a multiparametric scanning protocol including conventional imaging and T1-T2 mapping sequences. Abnormal T2 mapping was the most commonly abnormality observed in our cohort and positively correlated with hs-cTnT values, reflecting the predominant edematous changes characterizing the active phase of disease.

The purpose of our study was to compare diagnostic performance of old and new Lake Louise Criteria (oLLC and nLLC) among different clinical presentations: infarct-like (IL), cardiomyopathic (CM) and arrhythmic (AR). 102 patients with clinical suspicion of acute myocarditis underwent cardiac magnetic resonance (CMR) on a 1.5 T scanner. Protocol included cine-SSFP, T2-weighted STIR, T2 mapping, early and late gadolinium enhancement and T1 mapping acquired before and after gadolinium administration. The degree of agreement has been calculated with Cohen's K test. 42 patients also underwent endomyocardial biopsy (EMB). IL onset was present in 54/102 patients, CM in 28/102 and AR in 20/102. nLLC were positive in 58.3% of the patients, while oLLC in 37.9%, k = 0.57 (IC: 0.428-0.713). The degree of agreement between nLLC and oLLC was 0.49 (IC: 0.111-0.876) for AR onset (nLLC positive in 35% vs oLLC in 15%), 0.25 (IC: 0.035-0.459) for CM pattern (nLLC positive in 60.7% vs oLLC 17.9%) and 0.73 (IC: 0.543-0.912) for IL presentation (nLLC positive in 66.7% vs oLLC in 57.4%). Diagnostic accuracy was 75% for both nLLC and oLLC among IL onset, and 41.6% for oLLC vs 66.7% for nLLC, as regards CM clinical presentation. nLLC have improved diagnostic performance of CMR for the diagnosis of acute myocarditis, in particular for atypical clinical presentation.

Clinical manifestations of COVID-19 patients are dominated by respiratory symptoms, but cardiac complications are commonly observed and associated with increased morbidity and mortality. Underlying pathological mechanisms of cardiac injury are still not entirely elucidated, likely depending on a combination of direct viral damage with an uncontrolled immune activation. Cardiac involvement in these patients ranges from a subtle myocardial injury to cardiogenic shock. Advanced cardiac imaging plays a key role in discriminating the broad spectrum of differential diagnoses. Present article aims to review the value of advanced multimodality imaging in patients with suspected SARS-CoV-2-related cardiovascular involvement and its essential role in risk stratification and tailored treatment strategies. Based on our experience, we also sought to suggest possible diagnostic algorithms for the rationale utilization of advanced imaging tools, such as cardiac CT and CMR, avoiding unnecessary examinations and diagnostic delays.

Purpose: The aim of this study was to evaluate the appropriateness of the cardiac computed tomography angiography (CCTA) prescriptions according to the "2010-Appropriate-Use-Criteria-for-Cardiac-Computed-Tomography-Angiography" (AUCCTA) and "Clinical-indication-for-CCTA" (CICCTA) among different specialities (Cardiologist [CA], General Practitioner [GP], Other Specialists [OS]) and prescribers' age., Materials and Methods: This is a single-centre, single-arm, cohort study. We prospectively enrolled 815 patients (October 2012-May 2019) who underwent a radiological outpatient visit, before CCTA examination. Prescriptions to the examination were categorized as follows: Appropriate (A), Uncertain (U) and Inappropriate (Ina), according to AUCCTA and I, II, III and Inv for CICCTA. This categorization was stratified according to CA, GP and OS and prescribers' age. CCTA was performed in patients whom indications belong to A/U categories., Results: Eight hundred and fifteen CCTA prescriptions were analysed. An yearly increase in prescriptions was found in the eight-year observational period (2012/2019 projection: 72 vs 223). Considering AUCCTA, indication A was 540/815 (66.3%), indication U was 113/815 (13.9%) and Ina accounted for 162/815 (19.9%; 128/162 [79.0%] indications with stress test listed as criterium of inappropriateness). Only U indications decreased over years (p = 0.003). Regarding CICCTA, 501/815 (61.5%) patients were categorized as I, 144/815 (17.7%) as II, 102/815 (12.5%) as III, 67/815 (8.2%) were INV and 1/815 (0.1%) were non-classified. Clinical referrals were CA in 495/786 (63.0%), GPs in 57/786 (7.3%) GP and OS in 234/786 (29.8%) [p < 0.01]. No statistically significant differences were observed in the appropriateness among different specialty physicians. Younger doctors have a lower chance to not meet A indication (OR 0.98 [CI 95% 0.96-0.99]; p = 0.003)., Conclusion: Our study highlights the importance of a pre-radiological visit prior to CCTA, which prevented execution of 19.9% of inappropriate examinations. Age of prescribers had an impact on appropriateness, with younger doctors having a lower chance to not meet A indication.

The purpose of this article is to provide an overview on the role of CT scan and MRI according to selected guidelines by the European Society of Cardiology (ESC) and the American College of Cardiology/American Heart Association (ACC/AHA). ESC and ACC/AHA guidelines were systematically reviewed for recommendations to CT and MRI use in specific cardiovascular (CV) clinical categories. All recommendations were collected in a dataset, including the class of recommendation, the level of evidence (LOE), the specific imaging technique, the clinical purpose of the recommendation and the recommending Society. Among the 43 included guidelines (ESC: n = 18, ACC/AHA: n = 25), 26 (60.4%) contained recommendations for CT scan or MRI (146 recommendations: 62 for CT and 84 for MRI). Class of recommendation IIa (32.9%) was the most represented, followed by I (28.1%), IIb (24%) and III (11.9%). MRI recommendations more frequently being of higher class (I: 36.9%, IIa: 29.8%, IIb: 21.4%, III: 11.9%) as compared to CT (I: 16.1%, IIa: 37.1%, IIb: 27.4%, III: 19.4%). Most of recommendation (55.5%) were based on expert opinion (LOE C). The use of cardiac CT and cardiac MR in the risk assessment, diagnosis, therapeutic and procedural planning is in continuous development, driven by an increasing need to evolve toward an imaging-guided precision medicine, combined with cost-effectiveness and healthcare sustainability. These developments must be accompanied by an increased availability of high-performance scanners in healthcare facilities and should emphasize the need of increasing the number of radiologists fully trained in cardiac imaging.

Cerebrospinal fluid (CSF) plays an important role in solute clearance and maintenance of brain homeostasis. 11 C-Pittsburgh compound B (PiB) PET was recently proposed as a tool for detection of CSF clearance alterations in Alzheimer disease. The current study investigates the magnitude of 11 C-PiB PET signal in the lateral ventricles of an independent group of Alzheimer and mild cognitive impairment subjects. We have also evaluated multiple sclerosis as a model of disease with CSF clearance alterations without amyloid-β tissue accumulation. Methods: A set of 11 Alzheimer and 12 mild cognitive impairment subjects and a set of 20 multiple sclerosis subjects with matched controls underwent MRI and dynamic 11 C-PiB PET. Lateral ventricle regions of interest were generated manually from MRI data. PET data were analyzed using cerebellum or a supervised reference region for the Alzheimer and multiple sclerosis data sets, respectively. The magnitude of 11 C-PiB signal in the lateral ventricles was calculated as area under the curve from 35 to 80 min and SUV ratio (SUVR) from 50 to 70 min. Compartmental modeling analysis was performed on a separate data set containing 11 Alzheimer and matched control subjects; this analysis included an arterial input function, to further understand the kinetics of the lateral ventricular 11 C-PiB signal. Results: ANOVA revealed significant group differences in lateral ventricular SUVR across the Alzheimer, mild cognitive impairment, and healthy control groups ( P = 0.004). Pairwise comparisons revealed significantly lower lateral ventricular SUVR in Alzheimer subjects than in healthy controls ( P < 0.001) or mild cognitive impairment subjects ( P = 0.029). Lateral ventricular SUVR was significantly lower in multiple sclerosis subjects than in healthy controls ( P = 0.008). Compartmental modeling analysis revealed significantly lower uptake rates of 11 C-PiB signal from blood ( P = 0.005) and brain tissue ( P = 0.004) to the lateral ventricles and significantly lower 11 C-PiB signal clearance out of the lateral ventricles ( P = 0.002) in Alzheimer subjects than in healthy controls. Conclusion: These results indicate that dynamic 11 C-PiB PET can be used to observe pathologic changes in CSF dynamics. We have replicated previous work demonstrating CSF clearance deficits in Alzheimer disease associated with amyloid-β deposits and have extended the observations to include ventricular CSF clearance deficits in mild cognitive impairment and multiple sclerosis., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Healthy young women who engage in an exercise program may lose fat that is not reflected in body weight changes because of concurrent gains in fat-free mass (FFM)., Objective: This study addressed the question of how well anthropometry-based predictive equations can resolve these changes., Design: Several widely used skinfold-thickness- or circumference-based equations were compared by using dual-energy X-ray absorptiometry to study 150 healthy young women before and after 8 wk of Army basic combat training (average energy expenditure: 11.7 MJ/d)., Results: Women lost 1.2 +/- 2.6 kg fat (mean +/- SD) and gained 2.0 [corrected] +/- 1.5 kg FFM. Fat loss (r = 0.47), but not FFM gain (r = 0.01), correlated with initial fatness. Thus, for many women who lost fat, body weight did not change or increased. Fat loss was associated with a reduction in abdominal circumference but this alone was not a consistent marker of fat loss. One circumference equation and one skinfold-thickness equation yielded the smallest residual SDs (2.0% and 1.9% body fat, respectively) compared with the other equations in predicting body fat. The sensitivity and specificity of the best equations in predicting changes in percentage body fat were not better than 55% and 66%, respectively., Conclusions: These data suggest that for women, anthropometry can provide better estimates of fatness than body mass index but it is still relatively insensitive to short-term alterations in body composition. Not surprisingly, the circumference equation that includes the most labile sites of female fat deposition (ie, waist and hips instead of upper arm or thigh) proved to be the most reliable.

We tested the hypothesis that key endocrine responses to semistarvation would be attenuated by changing only the food intake in a multistressor environment that also included sustained workload, inadequate sleep, and thermal strain. Serum hormones were compared within and between two groups of healthy young male volunteers participating in the 8-wk US Army Ranger course, with four repeated cycles of restricted energy intakes and refeeding: group 1 (n = 49) and group 2 (n = 48); energy deficits averaged 1,200 and 1,000 kcal/day, respectively. After 8 wk, most of group 1 achieved a minimum body fat, serum 3,5,3'-triiodothyronine (T(3)) was below normal (78 +/- 20 ng/dl), testosterone (T) approached castrate levels (4.5 +/- 3.9 nmol/l), insulin-like growth factor I (IGF-I) declined by one-half (75 +/- 25 microg/l), and cholesterol rose from 158 +/- 31 to 217 +/- 39 mg/dl. Bioavailable T(3) and T were further reduced by increases in their specific binding proteins in response to declining insulin. Refeeding, even with continuation of the other stressors, produced prompt recovery of T(3), T, and IGF-I. Higher energy intakes in group 2 attenuated the subclinical hypothyroidism and hypercholesterolemia, whereas consistent luteinizing hormone suppression indicated centrally mediated threshold effects on gonadal hormone suppression. We conclude that low T, T(3), and IGF-I remained reliable markers of acute energy deficits in the presence of other stressors; elevated cholesterol and cortisol provided information about chronic status, corresponding to diminishing body fat stores.

The purpose of this study was to investigate the acute responses of both stress and fluid regulatory hormones to a single bout of resistance exercise in both trained and untrained men. Seven competitive power lifters (PL) and 12 untrained subjects (UT) performed one set of the leg press exercise to exhaustion at 80% of their respective one-repetition maximum. Blood samples were obtained twice prior to exercise (at P1 and P2), immediately postexercise (IP), and at 5 minutes postexercise (5PE). Compared to P1 and P2, plasma epinephrine, norepinephrine, dopamine, atrial peptide, osmolality, and blood lactic acid increased significantly (p < or = 0.05) at IP. Plasma epinephrine, norepinephrine, atrial peptide, and blood lactic acid concentrations remained elevated at 5PE compared to P1 and P2. Plasma renin activity and angiotensin II were significantly elevated at 5PE compared to P1, P2, and IP, and this increase was significantly greater in PL compared to UT at 5PE. These data indicate that an acute bout of resistance exercise dramatically affects secretion of stress and fluid regulatory hormones.

Coronary heart disease is the leading cause of death in the United States, accounting for almost half of all deaths. Animal studies have suggested that the daily addition of "hyperimmune egg" to one's diet might reduce the risk of cardiovascular disease. Military personnel with initial total cholesterol levels higher than 180 mg/dl were randomly enrolled in a 26-week double-blind study of a drink containing a hyperimmune egg protein. Subjects were randomly assigned to three groups: control (no drink); placebo (drink without egg); and active (drink combined with hyperimmune egg). Throughout the study this physically fit group maintained a program of strenuous exercise and participated in a dietary education program intended to reduce fat and cholesterol intake. At the end of the trial, total cholesterol levels of the control and placebo groups had increased, whereas the group that consumed the drink with hyperimmune egg showed no significant change in total cholesterol. The ratio of total cholesterol to high-density lipoproteins and the apolipoprotein B level increased in both control and placebo groups but remained essentially unchanged in the group consuming hyperimmune egg. Triglyceride and apolipoprotein A-I values did not change significantly in any of the groups. These findings suggest that hyperimmune egg may beneficially modify the regulation of serum lipoprotein levels and thereby reduce the possibility of cardiovascular diseases.

The abdomen is the principal site of fat deposition in men, and because abdominal fat is readily mobilized during exercise, the relative proportion of fat in the abdominal site may negatively correlate with the amount of regular physical activity, and even with physical fitness. This study presents data for regional fatness in 165 fit young men (U.S. Army Ranger candidates; initial body fat = 14.7 +/- 4.7%) assessed by dual-energy x-ray absorptiometry (DEXA), and for relative changes occurring following a 13% weight loss produced by a 1000 kcal.d-1 energy deficit over 8 wk. Fat-free mass was constant across quintiles of percent body fat; only fat mass was different (16.2 +/- 2.2 kg and 6.0 +/- 1.4 kg at upper and lower quintiles, respectively). Truncal fat accounted for about 41% of total body fat in all quintiles; only the proportion of fat distributed to the arms was significantly higher in the fattest quintiles of men. Among a group of less intensely trained soldiers with the same average fatness as the highest quintile of Ranger students (20%), relative fat distribution to the trunk approached 50% of the total fat. Following weight loss, Ranger students lost half of the fat in all regions assessed (legs, arms, and trunk). The only significant association between regional losses and initial fatness was a greater proportion of fat lost from the arms in the fattest Rangers. These data suggest a "fit fat" distribution in active young men in which fat remains in the arms and legs until extreme weight loss occurs and the metabolically more active abdominal fat approaches depletion.

To assess the benefits of Army nutrition initiatives reducing intakes of fat and cholesterol, the authors studied the dietary intakes of cadets at the U.S. Military Academy and compared these results and related nutritional indicators (body composition, serum lipid status) to data obtained one decade earlier. The regular Cadet Mess menu provided 16.6 MJ/day of energy with 34% derived from fat. Actual intakes, including supplements, averaged 14.9 +/- 2.9 and 9.7 +/- 2.1 MJ/day for 119 male and 86 female cadets, respectively. Most cadets derived < 35% of energy from dietary fat (11% from saturated fatty acids), representing a significant reduction since the previous study, in which nearly one-third of cadets received 40 to 45% of calories from fats; cholesterol intakes were markedly reduced. Serum cholesterol levels were approximately 7% lower, but were less affected than predicted by the reductions in fat and cholesterol intakes; serum low-density lipoprotein-cholesterol was also significantly reduced. Fasting serum insulin correlated with saturated fat intake in female cadets, indicating another health risk factor affected by intakes. The authors conclude that nutrition initiatives reducing energy derived from fats and total cholesterol intake have had a beneficial effect on the nutritional status of this fit young population.

Reliability of body-fat estimation by a four-compartment model was tested in 10 subjects. Body densities were measured by underwater weighing (UWW), total body water (TBW) by deuterium dilution, and total body bone mass (TBBM) by dual-energy x-ray absorptiometry in three sessions in 1 wk. Percent body fat was determined by [2.559/density -0.734 (TBW/weight) +0.983 (TBBM/weight) -1.841] x 100. Reliability coefficients were 0.991 and 0.994, and within-subjects standard deviations were +/- 1.0 and +/- 1.1 for percent body-fat estimations from Siri's two-compartment and the four-compartment models, respectively; fat mass was +/- 0.8 kg with both models. These data suggest that additive errors in the multicompartment model do not offset the improved accuracy of fat estimations over those obtained from UWW alone. The greatest source of error came from UWW procedure itself (+/- 0.002 g/cm3, or approximately 1.0% of body weight), followed by error in TBW (+/- 0.5 L). More reproducible passive methods that are not dependent on hydration or TBBM may be especially useful after validation against the four-compartment model.

Eucaryotic transcription initiation by RNA polymerase II involves protein:DNA interactions during the formation of a transcription complex. In addition to RNA polymerase II there are at least five other general transcription factors necessary for initiation with the adenovirus major late promoter. One of these, TFIIA, is involved in the earliest events during transcription complex assembly. We have purified TFIIA from wheat germ and characterized it in an in vitro transcription system. Wheat TFIIA is a single polypeptide of Mr approximately 35 kd which functionally replaces human (HeLa) TFIIA to form a wheat/HeLa transcription system. [This polypeptide can be eluted from a SDS-polyacrylamide gel, refolded to a native conformation, and will function as wheat TFIIA in the heterologous system.] The heterologous system requires a lower optimal incubation temperature than the HeLa system. Biochemical characterization, using the adenovirus major late promoter, indicates that transcription reaction parameters for both wheat and HeLa TFIIA are similar but the kinetics of transcription for both TFIIAs are somewhat dissimilar. A plant viral promoter, the cauliflower mosaic virus 35S promoter, accurately and efficiently directs in vitro transcription in both the wheat/HeLa and HeLa systems with identical transcription kinetics. We conclude that TFIIA function has been conserved during evolution.

Transcription factor IIA (TFIIA) is a necessary component of many RNA polymerase II transcription complexes. Assembly of the transcription complex begins when TFIIA interacts with the promoter. We have previously purified wheat germ TFIIA to homogeneity and demonstrated that it substitutes for human TFIIA in a human in vitro transcription system which utilizes the adenovirus-2 major late promoter (Ad-2 MLP). We now show, by gel retardation assays, that wheat TFIIA interacts with the Ad-2 MLP. Extensively purified human (HeLa) TFIIA interacts with the Ad-2 MLP similarly. Both wheat and human TFIIA interact with a DNA fragment comprising the minimal promoter region (-51/+32) but not with upstream or downstream regions. With both TFIIAs multiple complexes form; the fastest wheat TFIIA/DNA complex appears to be larger than the corresponding human TFIIA/DNA complex. Limited point mutation analysis of the Ad-2 MLP demonstrates that changes at -30 (TATAA region), +1, and -1 diminish TFIIA binding, but a change at -40 does not. DNA footprint analysis of this region is not definitive, but does indicate that following TFIIA binding there are changes in the pattern of hypersensitive sites.

The purpose of this study was to evaluate the effects of graded treadmill exercise on plasma preproenkephalin peptide F immunoreactivity and concomitant catecholamine responses at sea level (elevation, 50 m). Few data exist regarding the sea-level responses of plasma peptide F immunoreactivity to exercise. thirty-five healthy men performed a graded exercise test on a motor-driven treadmill at the relative exercise intensities of 25, 50, 75, and 100% of maximum oxygen consumption (VO2max). Significant (P less than 0.05) increases above rest were observed for plasma peptide F immunoreactivity and norepinephrine at 75 and 100% of the VO2 max and at 5 min into recovery. Significant increases in plasma epinephrine were observed at 75 and 100% of VO2max. Whole blood lactate significantly increased above resting values at 50, 75, and 100% of the VO2max and at 5 min into recovery. These data demonstrate that exercise stress increases plasma peptide F immunoreactivity levels at sea level. While the exercise response patterns of peptide F immunoreactivity are similar to catecholamines and blood lactate responses, no bivariate relationships were observed. These data show that sea-level response patterns to graded exercise are similar to those previously observed at moderate altitude (elevation, 2200 m).

The purpose of this study was to examine the effects of three different run training programs on plasma responses of beta-endorphin (beta-EP), adrenocorticotropin (ACTH), and cortisol to maximal treadmill exercise. Subjects were randomly assigned to one of three training groups: sprint intervals (SI) (N = 8), endurance (E) (N = 10), or combination (C) (N = 7). Training was monitored for 10 wk, and maximal treadmill exercise tests were administered pre-training and after 2, 4, 6, 8, and 10 wk of training. Blood samples were obtained (pre-training and after 10 wk) before, immediately after, and 5 and 15 min following the maximal exercise tests. All groups significantly (P less than 0.05) increased maximal oxygen consumption values at 8 and 10 wk of the training period. Significant exercise-induced increase in plasma beta-EP, ACTH, cortisol, and blood lactate were observed for both pre- and post-training tests in all training groups. The SI group demonstrated significant post-training increases in beta-EP, ACTH, cortisol, and 5 min post-exercise blood lactate concentrations in response to maximal exercise. No training-induced hormonal changes were observed for the E group. While exercise-induced increases were observed, the C group exhibited significant post-training reductions in plasma responses of beta-EP, ACTH, and blood lactate concentrations in response to maximal exercise. Still, resting and post-exercise increases in plasma cortisol concentrations were significantly higher in magnitude in the post-training test. Lactate was significantly correlated with beta-EP (r = 0.72), ACTH (r = 0.70), and cortisol (r = 0.64).(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to examine the resting and exercise response patterns of plasma Peptide F immunoreactivity (ir) to altitude exposure (4300 m) and caffeine ingestion (4 mg.kg b.w.-1). Nine healthy male subjects performed exercise tests to exhaustion (80-85% VO2max) at sea level (50 m), during an acute altitude exposure (1 hr, hypobaric chamber, 4300 m) and after a chronic (17-day sojourn, 4300 m) altitude exposure. Using a randomized, double-blind/placebo experimental design, a placebo or caffeine drink was ingested 1 hour prior to exercise. Exercise (without caffeine) significantly (p less than 0.05) increased plasma Peptide F ir values during exercise at chronic altitude only. Caffeine ingestion significantly increased plasma Peptide F ir concentrations during exercise and in the postexercise period at sea level. Conversely caffeine ingestion at altitude resulted in significant reductions in the postexercise plasma Peptide F ir values. The results of this study demonstrate that the exercise and recovery response patterns of plasma Peptide F ir may be significantly altered by altitude exposure and caffeine ingestion. These data support further study examining relationships between Peptide F (and other enkephalin-containing polypeptides) and epinephrine release in response to these types of physiological stresses.

No data exists regarding responses of human atrial natriuretic factor (ANF) to exercise in the heat. The purpose of this study was to examine the responses of plasma ANF to high intensity submaximal (71% +/- 0.9 VO2max) exercise in the heat over an eight day acclimation period. Fourteen healthy males volunteered to participate in the study. Subjects performed intermittent exercises on a treadmill (0% grade) during 50 min of each 100 min trial in an environmental chamber maintained at 41.2 +/- 0.5 degrees C, 39.0 +/- 1.7% relative humidity. Blood was obtained from an antecubital vein after standing 20 min in the heat prior to exercise, and immediately after exercise. Measures were compared on days 1, 4 and 8. ANF did not change pre- to post-exercise nor did it change over the eight day heat acclimation period despite other heat acclimation adaptations. Conversely, plasma aldosterone (ALDO), renin activity (PRA) and cortisol (COR) all increased (p less than 0.05) pre- to post-exercise on each day but again no changes were observed over the eight day period. These data support that ANF may not increase when ALDO and PRA increases are observed.

Plasma beta-endorphin, Met-enkephalin and Peptide F immunoreactivity (ir) were measured at rest and following exercise on three days (days 1, 4, 8) of an eight day heat acclimation regime. Fourteen male subjects demonstrated physiological heat acclimation adaptations. Our data demonstrated a differential response of peripheral plasma levels of endogenous opioid peptides (EOP) to exercise in the heat. In addition, EOP did not follow the same time-course of other physiological adaptations as no differences (day 1 vs. 4 vs. 8) in resting or exercise levels were observed over the eight day heat acclimation regime. Significant increases in beta-endorphin ir (pre- to post-exercise) appear to reflect concomitant exercise-heat related changes. The increased peripheral levels of beta-endorphin were correlated to plasma levels of cortisol. Heat and exercise stress may result in a reduction of Met-enkephalin ir observed in peripheral plasma and might be due to degradation or a decrease in processing from the larger precursors. The differential responses of EOP suggest the possibility of separate physiological roles for these peptides during exercise in the heat but peripheral plasma levels of EOP do not appear to reflect acute heat acclimation changes.