Imaging biomarkers in cardiac CT: moving beyond simple coronary anatomical assessment.

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.

Effectiveness of clinical scores in predicting coronary artery disease in familial hypercholesterolemia: a coronary computed tomography angiography study.

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.

T2-mapping increase is the prevalent imaging biomarker of myocardial involvement in active COVID-19: a Cardiovascular Magnetic Resonance study.

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.

Giant caseous mitral annular calcification mimicking ventricular pseudoaneurysm.

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.

Tocilizumab effects in COVID-19 pneumonia: role of CT texture analysis in quantitative assessment of response to therapy.

PURPOSE: To evaluate CT and laboratory changes in COVID-19 patients treated with tocilizumab, compared to a control group, throughout a combined semiquantitative and texture analysis of images. MATERIALS AND METHODS: From March 11 to April 20, 2020, 57 SARS-CoV-2 positive patients were retrospectively compared: group T (n = 30) receiving tocilizumab and group non-T (n = 27) undergoing only antivirals/antimalarials. Chest-CT and laboratory findings were analyzed before and after treatment. CT evaluation included both semiquantitative scoring and texture analysis of all parenchymal lesions. Survival and recovery analyses were also provided with Kaplan-Meier method. RESULTS: In group T, no significant differences were found for CT score after treatment, while several texture features significantly changed, including mean attenuation (p < 0.0001), skewness (p < 0.0001), entropy (p = 0.0146) and higher-order parameters, suggesting considerable fading of parenchymal lesions. PaO2/FiO2 mean value significantly increased after treatment, from 240 ± 93 to 363 ± 107 (p = 0.0003), with parallel decrease in inflammatory biomarkers (CRP, D-dimer and LDH). In group non-T, CT scoring, texture and laboratory parameters showed significant worsening at follow-up. Findings were clinically associated with opposite trends between two groups, with reduction of severe cases in group T (from 21/30 to 5/30; p < 0.0001) as compared to a significant worsening in group non-T (severe cases increasing from 6/27 to 14/27; p = 0.0473). Probability of discharge was significantly higher in group T (p < 0.0001), as well as survival rate, although not statistically significant. CONCLUSIONS: Our results suggest the potential role of CT texture analysis for assessing response to treatment in COVID-19 pneumonia, using Tocilizumab, as compared to semiquantitative evaluation, providing insight into the intrinsic parenchymal changes.

Takotsubo syndrome: left atrial and ventricular myocardial strain impairment in the subacute and convalescent phases assessed by CMR.

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_r), conduit (laS_cd), and booster pump strain (laS_bp) and strain rate (laSR_r, laSR_cd, laSR_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_bp (12.7% versus 9.8%) and reduced lvEF (47.4% versus 54.8%), lvGLS (-12.2% versus 14.6%), and laS_cd (7.0% versus 9.5%) compared to cTTS (p ≤ 0.029). The interval between symptoms onset and CMR was correlated with laS_bp (r = -0.49) and lvGLS (r = 0.47) (p = 0.001 for both). At receiver operating characteristics analysis, laS_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_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.

Papillary Muscle Involvement during Acute Myocardial Infarction: Detection by Cardiovascular Magnetic Resonance Using T1 Mapping Technique and Papillary Longitudinal Strain.

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.

Protective Value of Aspirin Loading Dose on Left Ventricular Remodeling After ST-Elevation Myocardial Infarction.

Aims: Left ventricular (LV) remodeling after ST-elevation myocardial infarction (STEMI) is a complex process, defined as changes of LV volumes over time. CMR feature tracking analysis (CMR-FT) offers an accurate quantitative assessment of LV wall deformation and myocardial contractile function. This study aimed to evaluate the role of myocardial strain parameters in predicting LV remodeling and to investigate the effect of Aspirin (ASA) dose before primary coronary angioplasty (pPCI) on myocardial injury and early LV remodeling. Methods and Results: Seventy-eight patients undergoing CMR, within 9 days from symptom onset and after 6 months, were enrolled in this cohort retrospective study. We divided the study population into three groups based on a revised Bullock's classification and we evaluated the role of baseline CMR features in predicting early LV remodeling. Regarding CMR strain analysis, worse global circumferential and longitudinal strain (GCS and GLS) values were associated with adverse LV remodeling. Patients were also divided based on pre-pPCI ASA dosage. Significant differences were detected in patients receiving ASA 500 mg dose before pPCI, which showed lower infarct size extent and better strain values compared to those treated with ASA 250 mg. The stepwise multivariate logistic regression analysis, adjusted for covariates, indicated that a 500 mg ASA dose remained an inverse independent predictor of early adverse LV remodeling. Conclusion: GCS and GLS have high specificity to detect early LV adverse remodeling. We first reported a protective effect of ASA loading dose of 500 mg before pPCI on LV myocardial damage and in reducing early LV adverse remodeling.

Impaction of regurgitation jet on anterior mitral leaflet is associated with diastolic dysfunction in patients with bicuspid aortic valve and mild insufficiency: a cardiovascular magnetic resonance study.

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.

Role of advanced imaging in COVID-19 cardiovascular complications.

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.

4D flow imaging of the thoracic aorta: is there an added clinical value?

Four-dimensional (4D) flow MRI has emerged as a powerful non-invasive technique in cardiovascular imaging, enabling to analyse in vivo complex flow dynamics models by quantifying flow parameters and derived features. Deep knowledge of aortic flow dynamics is fundamental to better understand how abnormal flow patterns may promote or worsen vascular diseases. In the perspective of an increasingly personalized and preventive medicine, growing interest is focused on identifying those quantitative functional features which are early predictive markers of pathological evolution. The thoracic aorta and its spectrum of diseases, as the first area of application and development of 4D flow MRI and supported by an extensive experimental validation, represents the ideal model to introduce this technique into daily clinical practice. The purpose of this review is to describe the impact of 4D flow MRI in the assessment of the thoracic aorta and its most common affecting diseases, providing an overview of the actual clinical applications and describing the potential role of derived advanced hemodynamic measures in tailoring follow-up and treatment.

Splenic Blood Flow Increases after Hypothermic Stimulus (Cold Pressor Test): A Perfusion Magnetic Resonance Study.

The Cold Pressor Test (CPT) is a novel diagnostic strategy to noninvasively assess the myocardial microvascular endothelial-dependent function using perfusion magnetic resonance imaging (MRI). Spleen perfusion is modulated by a complex combination of several mechanisms involving the autonomic nervous system and vasoactive mediators release. In this context, the effects of cold temperature on splenic blood flow (SBF) still need to be clarified. Ten healthy subjects were studied by MRI. MRI protocol included the acquisition of GRE T1-weighted sequence ("first pass perfusion") during gadolinium administration (0.1mmol/kg of Gd-DOTA at flow of 3.0 ml/s), at rest and after CPT. Myocardial blood flow (MBF) and SBF were measured by applying Fermi function deconvolution, using the blood pool input function sampled from the left ventricle cavity. MBF and SBF values after performing CPT were significantly higher than rest values (SBF at rest: 0.65 ± 0.15 ml/min/g Vs. SBF after CPT: 0.90 ± 0.14 ml/min/g, p: <0.001; MBF at rest: 0.90 ± 0.068 ml/min/g Vs. MBF after CPT: 1.22 ± 0.098 ml/min/g, p<0.005). Both SBF and MBF increased in all patients during the CPT. In particular, the CPT-induced increase was 43% ± 29% for SBF and 36.5% ± 17% for MBF. CPT increases SBF in normal subjects. The characterization of a standard perfusion response to cold might allow the use of the spleen as reference marker for the adequacy of cold stimulation during myocardial perfusion MRI.