Computed tomography and nuclear medicine for the assessment of coronary inflammation: clinical applications and perspectives.

There is increasing evidence that in patients with atherosclerotic cardiovascular disease (ASCVD) under optimal medical therapy, a persisting dysregulation of the lipid and glucose metabolism, associated with adipose tissue dysfunction and inflammation, predicts a substantial residual risk of disease progression and cardiovascular events. Despite the inflammatory nature of ASCVD, circulating biomarkers such as high-sensitivity C-reactive protein and interleukins may lack specificity for vascular inflammation. As known, dysfunctional epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT) produce pro-inflammatory mediators and promote cellular tissue infiltration triggering further pro-inflammatory mechanisms. The consequent tissue modifications determine the attenuation of PCAT as assessed and measured by coronary computed tomography angiography (CCTA). Recently, relevant studies have demonstrated a correlation between EAT and PCAT and obstructive coronary artery disease, inflammatory plaque status and coronary flow reserve (CFR). In parallel, CFR is well recognized as a marker of coronary vasomotor function that incorporates the haemodynamic effects of epicardial, diffuse and small-vessel disease on myocardial tissue perfusion. An inverse relationship between EAT volume and coronary vascular function and the association of PCAT attenuation and impaired CFR have already been reported. Moreover, many studies demonstrated that 18F-FDG PET is able to detect PCAT inflammation in patients with coronary atherosclerosis. Importantly, the perivascular FAI (fat attenuation index) showed incremental value for the prediction of adverse clinical events beyond traditional risk factors and CCTA indices by providing a quantitative measure of coronary inflammation. As an indicator of increased cardiac mortality, it could guide early targeted primary prevention in a wide spectrum of patients. In this review, we summarize the current evidence regarding the clinical applications and perspectives of EAT and PCAT assessment performed by CCTA and the prognostic information derived by nuclear medicine.

Cardiovascular magnetic resonance images with susceptibility artifacts: artificial intelligence with spatial-attention for ventricular volumes and mass assessment.

BACKGROUND: Segmentation of cardiovascular magnetic resonance (CMR) images is an essential step for evaluating dimensional and functional ventricular parameters as ejection fraction (EF) but may be limited by artifacts, which represent the major challenge to automatically derive clinical information. The aim of this study is to investigate the accuracy of a deep learning (DL) approach for automatic segmentation of cardiac structures from CMR images characterized by magnetic susceptibility artifact in patient with cardiac implanted electronic devices (CIED). METHODS: In this retrospective study, 230 patients (100 with CIED) who underwent clinically indicated CMR were used to developed and test a DL model. A novel convolutional neural network was proposed to extract the left ventricle (LV) and right (RV) ventricle endocardium and LV epicardium. In order to perform a successful segmentation, it is important the network learns to identify salient image regions even during local magnetic field inhomogeneities. The proposed network takes advantage from a spatial attention module to selectively process the most relevant information and focus on the structures of interest. To improve segmentation, especially for images with artifacts, multiple loss functions were minimized in unison. Segmentation results were assessed against manual tracings and commercial CMR analysis software cvi42(Circle Cardiovascular Imaging, Calgary, Alberta, Canada). An external dataset of 56 patients with CIED was used to assess model generalizability. RESULTS: In the internal datasets, on image with artifacts, the median Dice coefficients for end-diastolic LV cavity, LV myocardium and RV cavity, were 0.93, 0.77 and 0.87 and 0.91, 0.82, and 0.83 in end-systole, respectively. The proposed method reached higher segmentation accuracy than commercial software, with performance comparable to expert inter-observer variability (bias ± 95%LoA): LVEF 1 ± 8% vs 3 ± 9%, RVEF - 2 ± 15% vs 3 ± 21%. In the external cohort, EF well correlated with manual tracing (intraclass correlation coefficient: LVEF 0.98, RVEF 0.93). The automatic approach was significant faster than manual segmentation in providing cardiac parameters (approximately 1.5 s vs 450 s). CONCLUSIONS: Experimental results show that the proposed method reached promising performance in cardiac segmentation from CMR images with susceptibility artifacts and alleviates time consuming expert physician contour segmentation.

Recommendations in pre-procedural imaging assessment for transcatheter aortic valve implantation intervention: Italian Society of Cardiology (SIC)-Italian Society of Medical and Interventional Radiology (SIRM) position paper part 1 (Clinical Indication and Basic Technical Aspects, Heart Team, Role of Echocardiography).

Non-invasive cardiovascular imaging owns a pivotal role in the preoperative assessment of patients for transcatheter aortic valve implantation (TAVI), providing a wide range of crucial information to select the patients who will benefit the most and have the procedure done safely. Although advanced cardiac imaging with cardiac computed tomography is routinely used for a detailed anatomic assessment before TAVI, echocardiography remains the first imaging modality to assess aortic stenosis severity and to provide essential functional information. This document results from the collaboration between the Italian Society of Cardiology (SIC) and the Italian Society of Medical and Interventional Radiology (SIRM), aiming to produce an updated consensus statement about the pre-procedural imaging assessment in patient for TAVI. The writing committee is composed of radiologists and cardiologists, experts in the field of cardiac imaging and structural heart diseases. Part 1 of the document, after a brief overview of the clinical indication and basic technical aspects of TAVI, will focus on the role of echocardiography in TAVI pre-procedural planning.

Plaque assessment by coronary CT angiography may predict cardiac events in high risk and very high risk diabetic patients: A long-term follow-up study.

BACKGROUND AND AIMS: The aim of the present study is to evaluate whether advanced coronary atherosclerosis analysis by CCTA may improve prognostic stratification among diabetic patients at high cardiovascular risk (CV risk). METHODS AND RESULTS: The study population consisted of 265 consecutive diabetic patients at high CV risk who underwent CCTA for suspected CAD between January 2011 and December 2016. For every patients both traditional and advanced, qualitative and quantitative coronary plaque analysis were performed. The occurrence of cardiac death, ACS, and non-urgent revascularization were recorded at follow-up. Among the 265 patients enrolled, 21 were lost to follow-up, whereas 244 (92%) had a complete follow-up (mean 45 ± 22 months) and were classified at high (n = 67) or very high cardiovascular risk (n = 177), according to ESC Guidelines. A total of 63 events were recorded (3 Cardiac Death, 3 NSTEMI, 8 unstable angina, 36 late non-urgent revascularization and 13 non-cardiac death) in 57 different patients. Elevated fibro-fatty plaque volume was the only predictor of events over age, gender and traditional risk factor when ACS and MACE were considered as end-points [HR (95% CI) 6.01 (1.65-21.87), p = 0.006 and 3.46 (2.00-5.97); p < 0.001]. CONCLUSION: The present study confirms the prognostic role of advance coronary atherosclerosis evaluation beyond risk factors and stenosis severity, even in diabetics. Despite the very high cardiovascular risk of study population, a not negligible portion (23%) of patients exhibited totally normal coronaries.

Clinical applications of cardiac computed tomography: a consensus paper of the European Association of Cardiovascular Imaging-part II.

Cardiac computed tomography (CT) was initially developed as a non-invasive diagnostic tool to detect and quantify coronary stenosis. Thanks to the rapid technological development, cardiac CT has become a comprehensive imaging modality which offers anatomical and functional information to guide patient management. This is the second of two complementary documents endorsed by the European Association of Cardiovascular Imaging aiming to give updated indications on the appropriate use of cardiac CT in different clinical scenarios. In this article, emerging CT technologies and biomarkers, such as CT-derived fractional flow reserve, perfusion imaging, and pericoronary adipose tissue attenuation, are described. In addition, the role of cardiac CT in the evaluation of atherosclerotic plaque, cardiomyopathies, structural heart disease, and congenital heart disease is revised.

Recommendations in pre-procedural imaging assessment for TAVI intervention: SIC-SIRM position paper part 2 (CT and MR angiography, standard medical reporting, future perspectives).

Non-invasive cardiovascular imaging owns a pivotal role in the preoperative assessment of patient candidates for transcatheter aortic valve implantation (TAVI), providing a wide range of crucial information to select the patients who will benefit the most and have the procedure done safely. This document has been developed by a joined group of experts of the Italian Society of Cardiology and the Italian Society of Medical and Interventional Radiology and aims to produce an updated consensus statement about the pre-procedural imaging assessment in candidate patients for TAVI intervention. The writing committee consisted of members and experts of both societies who worked jointly to develop a more integrated approach in the field of cardiac and vascular radiology. Part 2 of the document will cover CT and MR angiography, standard medical reporting, and future perspectives.

SIRM-SIC appropriateness criteria for the use of Cardiac Computed Tomography. Part 1: Congenital heart diseases, primary prevention, risk assessment before surgery, suspected CAD in symptomatic patients, plaque and epicardial adipose tissue characterization, and functional assessment of stenosis.

In the past 20 years, Cardiac Computed Tomography (CCT) has become a pivotal technique for the noninvasive diagnostic work-up of coronary and cardiac diseases. Continuous technical and methodological improvements, combined with fast growing scientific evidence, have progressively expanded the clinical role of CCT. Recent large multicenter randomized clinical trials documented the high prognostic value of CCT and its capability to increase the cost-effectiveness of the management of patients with suspected CAD. In the meantime, CCT, initially perceived as a simple non-invasive technique for studying coronary anatomy, has transformed into a multiparametric "one-stop-shop" approach able to investigate the heart in a comprehensive way, including functional, structural and pathophysiological biomarkers. 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 Medical and Interventional Radiology (SIRM) and by the Italian Society of Cardiology (SIC), represents the first of two consensus documents collecting the expert opinion of Radiologists and Cardiologists about current appropriate use of CCT.

Reliability of single breath hold three-dimensional cine kat-ARC for the assessment of biventricular dimensions and function.

PURPOSE: To assess the accuracy and reproducibility of 3D-cine k-adaptative-t-autocalibrating reconstruction for cartesian sampling (3D cine kat-ARC) for quantification of biventricular volumes, ejection fraction and LV mass in clinical practice. METHOD: 74 patients underwent cardiac magnetic resonance for clinical indications. In the whole population 3D cine kat-ARC and 2D cine bSSFP images were acquired on short axis view. Subsequently, the population was divided in three subgroups (dilated, hypetrophic, other phenotypes). Two experienced observers performed analysis of volumes, biventricular function and left ventricular mass in the overall population and subgroups using an off-line workstation. Statistical analysis was performed using Student's t-test, linear regression and Bland-Altman plot, correlation coefficient η2 and the intraclass correlation coefficient (ICC). A cut-off value of p < 0.05 was considered statistically significant. RESULTS: Biventricular volumes, function and left ventricular mass evaluated with 3D cine kat-ARC sequences did not show any significant difference compared to 2D bSSFP sequences in the overall population (p > 0.05). Bland-Altman analysis showed limited bias and narrow limits of the agreement for all measurements in overall population. Subgroup analysis showed a statistically significant difference (p = 0.04) for left ventricular ejection fraction (LVEF) in patients with a dilated phenotype; showing a minimum overestimation tendency for 3D cine kat ARC (2D cine bSSFP LVEF = 46.44 ± 15.83% vs 3D cine kat-ARC LVEF = 48.36 ± 16.50 %). CONCLUSIONS: 3D cine kat-ARC 3D sequences allow an accurate evaluation of biventricular volumes and function in a single breath hold.

Cardiovascular Events Recurrence and Coronary Artery Disease in HIV Patients: The Price We Have to Pay for the Chronicization of the Disease.

The introduction of combination of antiretroviral therapy and advancement in care of HIV have dramatically changed the natural history of patients living with HIV. Today, HIV+ patients have a life expectancy not significantly different from HIV uninfected people. However, concerns remain about all the comorbidities associated with aging and the effects of chronic therapies in such high-risk patients. HIV+ subjects exhibited accelerated atherosclerosis and have a 1.5- to 2-fold increased risk of having coronary artery disease (CAD), usually presenting early and aggressively with acute coronary events. Furthermore, HIV+ patients with CAD often complain recurrent acute coronary events, and they are plagued by major adverse cardiac outcomes. This review will focus on the current understanding of the CAD phenotype in HIV+ patients highlighting the topic of acute coronary event recurrence and underscoring the role of percutaneous management strategies in the light of information derived from invasive coronary imaging.

[Non-invasive functional assessment of coronary stenosis by cardiac computed tomography]. / Valutazione funzionale non invasiva della stenosi coronarica mediante tomografia computerizzata cardiaca.

The increased number of patients with coronary artery disease (CAD) is of great clinical relevance and involves a large burden of the healthcare system. The management of these patients is focused on relieving symptoms and improving clinical outcomes. Therefore, the ideal test would provide the correct diagnosis and actionable information. To this aim, several non-invasive functional imaging modalities are usually used as gatekeeper to invasive coronary angiography, but their diagnostic performance remains low with limited accuracy when compared to obstructive CAD at the time of invasive coronary angiography or invasive fractional flow reserve (FFR) assessment. For these reasons, an urgent need for non-invasive techniques that evaluate both the functional and morphological severity of CAD is growing. Coronary computed tomography angiography (CCTA) has emerged as a unique non-invasive technique providing coronary artery anatomic imaging. More recently, the evaluation of FFR with CCTA (FFRCT) has demonstrated high diagnostic performance compared to invasive FFR. Moreover, this tool has been proven to be more cost-effective than standard diagnostic pathways in large prospective multicenter trials, and to have a prognostic role. Additionally, stress myocardial computed tomography perfusion (stress CTP) represents a novel tool for the diagnosis of ischemia with high diagnostic accuracy. With advances in technical development, both static and dynamic computed tomography myocardial perfusion protocols offer functional assessment with an acceptable increase in radiation exposure. Compared to other imaging techniques, both FFRCT and stress CTP allow the combination of the anatomical evaluation of coronary arteries and the functional relevance of coronary artery lesions, having the potential to revolutionize the diagnostic paradigm of suspected CAD. FFRCT and stress CTP should be integrated in diagnostic pathways of patients with stable CAD and will likely result in a decrease of invasive diagnostic procedures and costs.

Design of CTP-PRO study (impact of stress Cardiac computed Tomography myocardial Perfusion on downstream resources and PROgnosis in patients with suspected or known coronary artery disease: A multicenter international study).

BACKGROUND: CT myocardial perfusion imaging (CTP) represents one of the newly developed CT-based techniques but its cost-effectiveness in the clinical pathway is undefined. The aim of the study is to evaluate the usefulness of combined evaluation of coronary anatomy and myocardial perfusion in intermediate to high-risk patients for suspected CAD or with known disease in terms of clinical decision-making, resource utilization and outcomes in a broad variety of geographic areas and patient subgroups. METHODS: CTP-PRO study is a cooperative, international, multicentre, prospective, open-label, randomized controlled study evaluating the cost-effectiveness of a CCTA+CTP strategy (Group A) versus usual care (Group B) in intermediate-high risk patients with suspected or known CAD who undergo clinically indicated diagnostic evaluation. A total sample size of 2000 subjects will be enrolled and followed up for 24 months. The primary endpoint is the reclassification rate of CCTA in group A due to the addition of CTP. The secondary endpoint will be the comparison between groups in terms of non-invasive and invasive downstream testing, prevalence of obstructive CAD at ICA, revascularization, cumulative ED and overall cost during the follow-up at 1- and 2-years. The tertiary endpoint will be the comparison between each group in terms of MACE and cost-effectiveness at 1- and 2-years. CONCLUSIONS: The study will provide information to patients, health care providers and other stakeholders about which strategy could be more effective in the diagnosis of suspected CAD in intermediate to high-risk patients or in the symptomatic patients with known CAD and previous history of revascularization.

Coronary Atherosclerosis Assessment by Coronary CT Angiography in Asymptomatic Diabetic Population: A Critical Systematic Review of the Literature and Future Perspectives.

The prognostic impact of diabetes mellitus (DM) on cardiovascular outcomes is well known. As a consequence of previous studies showing the high incidence of coronary artery disease (CAD) in diabetic patients and the relatively poor outcome compared to nondiabetic populations, DM is considered as CAD equivalent which means that diabetic patients are labeled as asymptomatic individuals at high cardiovascular risk. Lessons learned from the analysis of prognostic studies over the past decade have challenged this dogma and now support the idea that diabetic population is not uniformly distributed in the highest risk box. Detecting CAD in asymptomatic high risk individuals is controversial and, what is more, in patients with diabetes is challenging, and that is why the reliability of traditional cardiac stress tests for detecting myocardial ischemia is limited. Cardiac computed tomography angiography (CCTA) represents an emerging noninvasive technique able to explore the atherosclerotic involvement of the coronary arteries and, thus, to distinguish different risk categories tailoring this evaluation on each patient. The aim of the review is to provide a wide overview on the clinical meaning of CCTA in this field and to integrate the anatomical information with a reliable therapeutic approach.

The STRATEGY Study (Stress Cardiac Magnetic Resonance Versus Computed Tomography Coronary Angiography for the Management of Symptomatic Revascularized Patients): Resources and Outcomes Impact.

BACKGROUND: Computed tomography coronary angiography (cTCA) and stress cardiac magnetic resonance (stress-CMR) are suitable tools for diagnosing obstructive coronary artery disease in symptomatic patients with previous history of revascularization. However, performance appraisal of noninvasive tests must take in account the consequent diagnostic testing, invasive procedures, clinical outcomes, radiation exposure, and cumulative costs rather than their diagnostic accuracy only. We aimed to compare an anatomic (cTCA) versus a functional (stress-CMR) strategy in symptomatic patients with previous myocardial revascularization procedures. METHODS AND RESULTS: Six hundred patients with chest pain and previous revascularization included in a prospective observational registry and evaluated by clinically indicated cTCA (n=300, mean age 68.2±9.7 years, male 255) or stress-CMR (n=300, mean age 67.6±9.7 years, male 263) were enrolled and followed-up in terms of subsequent noninvasive tests, invasive coronary angiography, revascularization procedures, cumulative effective radiation dose, major adverse cardiac events, defined as a composite end point of nonfatal myocardial infarction and cardiac death, and medical costs. The mean follow-up for cTCA and stress-CMR groups was similar (773.6±345 versus 752.8±291 days; P=0.21). Compared with stress-CMR, cTCA was associated with a higher rate of subsequent noninvasive tests (28% versus 17%; P=0.0009), invasive coronary angiography (31% versus 20%; P=0.0009), and revascularization procedures (24% versus 16%; P=0.007). Stress-CMR strategy was associated with a significant reduction of radiation exposure and cumulative costs (59% and 24%, respectively; P<0.001). Finally, patients undergoing stress-CMR showed a lower rate of major adverse cardiac events (5% versus 10%; P<0.010) and cost-effectiveness ratio (119.98±250.92 versus 218.12±298.45 Euro/y; P<0.001). CONCLUSIONS: Compared with cTCA, stress-CMR is more cost-effective in symptomatic revascularized patients.

Prognostic Benefit of Cardiac Magnetic Resonance Over Transthoracic Echocardiography for the Assessment of Ischemic and Nonischemic Dilated Cardiomyopathy Patients Referred for the Evaluation of Primary Prevention Implantable Cardioverter-Defibrillator Therapy.

BACKGROUND: The aim of this study was to determine the prognostic benefit of cardiac magnetic resonance (CMR) over transthoracic echocardiography (TTE) in ischemic cardiomyopathy and nonischemic dilated cardiomyopathy patients evaluated for primary prevention implantable cardioverter-defibrillator therapy. METHODS AND RESULTS: We enrolled 409 consecutive ischemic and dilated cardiomyopathy patients (mean age: 64±12 years; 331 men). All patients underwent TTE and CMR, and left ventricle end-diastolic volume, left ventricle end-systolic volume, and left ventricle ejection fraction (LVEF) were evaluated. In addition, late gadolinium enhancement was also assessed. All patients were followed up for major adverse cardiac events (MACE) defined as a composite end point of long runs of nonsustained ventricular tachycardia, sustained ventricular tachycardia, aborted sudden cardiac death, or sudden cardiac death. The median follow-up was 545 days. CMR showed higher left ventricle end-diastolic volume (mean difference: 43±22.5 mL), higher left ventricle end-systolic volume (mean difference: 34±20.5 mL), and lower LVEF (mean difference: -4.9±10%) as compared to TTE (P<0.01). MACE occurred in 103 (25%) patients. Patients experiencing MACE showed higher left ventricle end-diastolic volume, higher left ventricle end-systolic volume, and lower LVEF with both imaging modalities and higher late gadolinium enhancement per-patient prevalence as compared to patients without MACE. At multivariable analysis, CMR-LVEF ≤35% (hazard ratio=2.18 [1.3-3.8]) and the presence of late gadolinium enhancement (hazard ratio=2.2 [1.4-3.6]) were independently associated with MACE (P<0.01). A model based on CMR-LVEF ≤35% or CMR-LVEF ≤35% plus late gadolinium enhancement detection showed a higher performance in the prediction of MACE as compared to TTE-LVEF resulting in net reclassification improvement of 0.468 (95% confidence interval, 0.283-0.654; P<0.001) and 0.413 (95% confidence interval, 0.23-0.63; P<0.001), respectively. CONCLUSIONS: CMR provides additional prognostic stratification as compared to TTE, which may have direct impact on the indication of implantable cardioverter-defibrillator implantation.