MRI-derived extracellular volume as a biomarker of cancer therapy cardiotoxicity: systematic review and meta-analysis.

OBJECTIVES: MRI-derived extracellular volume (ECV) allows characterization of myocardial changes before the onset of overt pathology, which may be caused by cancer therapy cardiotoxicity. Our purpose was to review studies exploring the role of MRI-derived ECV as an early cardiotoxicity biomarker to guide timely intervention. MATERIALS AND METHODS: In April 2022, we performed a systematic search on EMBASE and PubMed for articles on MRI-derived ECV as a biomarker of cancer therapy cardiotoxicity. Two blinded researchers screened the retrieved articles, including those reporting ECV values at least 3 months from cardiotoxic treatment. Data extraction was performed for each article, including clinical and technical data, and ECV values. Pooled ECV was calculated using the random effects model and compared among different treatment regimens and among those who did or did not experience overt cardiac dysfunction. Meta-regression analyses were conducted to appraise which clinical or technical variables yielded a significant impact on ECV. RESULTS: Overall, 19 studies were included. Study populations ranged from 9 to 236 patients, for a total of 1123 individuals, with an average age ranging from 12.5 to 74 years. Most studies included patients with breast or esophageal cancer, treated with anthracyclines and chest radiotherapy. Pooled ECV was 28.44% (95% confidence interval, CI, 26.85-30.03%) among subjects who had undergone cardiotoxic cancer therapy, versus 25.23% (95%CI 23.31-27.14%) among those who had not (p = .003). CONCLUSION: A higher ECV in patients who underwent cardiotoxic treatment could imply subclinical changes in the myocardium, present even before overt cardiac pathology is detectable. CLINICAL RELEVANCE STATEMENT: The ability to detect subclinical changes in the myocardium displayed by ECV suggests its use as an early biomarker of cancer therapy-related cardiotoxicity. KEY POINTS: • Cardiotoxicity is a common adverse effect of cancer therapy; therefore, its prompt detection could improve patient outcomes. • Pooled MRI-derived myocardial extracellular volume was higher in patients who underwent cardiotoxic cancer therapy than in those who did not (28.44% versus 25.23%, p = .003). • MRI-derived myocardial extracellular volume represents a potential early biomarker of cancer therapy cardiotoxicity.

Solving Intraoperative Complications During Endovascular Repair of Late Contained Ruptured Aortic Pseudoaneurysm After Surgical De-coarctation: Case Report and Systematic Review of Literature.

AIM: We present a case of successful endovascular repair of late ruptured aortic anastomotic pseudoaneurysm following previous left subclavian artery-descending thoracic aorta bypass and concomitant emergency thoracic endovascular aortic repair (TEVAR) of complicated endovascular aortic de-coarctation never previously described is also presented. A review of the intraoperative, 30-day, and follow-up morbidity, mortality, and complications of TEVAR as endovascular treatment of late aneurysm/pseudoaneurysms after surgical aortic de-coarctation was also performed. METHODS: The systematic review was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement and following PICO model. A literature search was conducted on MEDLINE, PubMed, EMBASE, Cochrane Library, Google Scholar, Science Direct, and Web of Science using the words "tevar of late complication of aortic coarctation surgical repair" and "endovascular repair of anastomotic pseudoaneurysm in coarctation" up to June 17, 2022. Data were extracted from study documents about study design, patient's demographics and comorbidities, details about primary surgical repair, type of late complication, time between open surgery and occurrence of complications, details of the secondary endovascular procedure with technical success, early, and follow-up mortality and morbidity. RESULTS: A total of 18 papers were included with 78 patients (48 men, 69.5%). The most frequent type of primary open surgical repair was patch aortoplasty (46, 58.9%). Focusing on aneurysm and pseudoaneurysm as late complications, most of the patients were asymptomatic (45, 57.7%). All patients underwent TEVAR, 14 of them (17.9%) in urgent/emergent setting. The technical success was 98.7%, with 1 intraoperative death due to rupture of the aorta. In total, 31 patients out of 78 (39.7%) showed different complications in the immediate postoperative time, with type II endoleak being the most observed (8/31, 25.8%). The mean follow-up time was about 2 years (26.5 months, range 3-92). Overall, 30-day mortality was 2.6%. Complications occurred in 30 patients (39.4%), 23 of them resolved during the follow-up period. CONCLUSIONS: With the limit of low-quality data, TEVAR can be considered a safe and effective option for the treatment of late complications after open surgery for aortic coarctation, even in urgent settings. CLINICAL IMPACT: Different specialists have to face the technical complexities and risks related to treatment of late complications after surgical de-coartaction, which can be either surgical or endovascular, and depend on patient's ages. Although covered stents appear to have some protection from the development of stent fractures, doesn't provide complete protection from late aneurysm formation. In this setting, TEVAR may represent a valuable option, combining the advantages of the covered stent with those of a device that can cover a wider range of aortic length, especially in adult patients. This study shows thoracic endovascular repair can be considered a safe and effective option in clincal practice for the treatment of late complications after open surgery for AC, even in urgent settings.

The predictive role of right ventricular late gadolinium enhancement in patients with tetralogy of Fallot undergoing pulmonary valve replacement.

BACKGROUND: Our purpose was to evaluate the correlations between right ventricular (RV) late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) in patients with tetralogy of Fallot (ToF) scheduled for pulmonary valve replacement (PVR) and post-PVR functional data. METHODS: We retrospectively reviewed ToF patients scheduled for PVR who underwent two CMR examinations at our institution, one before the procedure (CMR-0), including contrast-enhanced sequences, and one after the procedure (CMR-1). Functional left and RV data were obtained by segmenting short-axis stacks on both CMR examinations, and normalised variations were calculated by dividing differences between CMR-1 and CMR-0 by the intercurring time interval, whereas the RV scar burden was assessed on CMR-0 LGE sequences both semiquantitatively and quantitatively. Data were reported as median and interquartile range, differences were appraised with the Mann-Whitney U test, while correlations were assessed with Spearman's ρ. RESULTS: Fifteen patients with a median age of 25 years (16-29), including 9 (60%) males, with a median time interval between CMR-0 and CMR-1 of 17 months (12-23), were retrospectively reviewed. The semiquantitative LGE score at CMR-0 was 7 (6-9), and LGE volume was 4.49 mL (3.70-5.78), covering 5.63% (4.92-7.00) of the RV. RV LGE score showed a moderate positive correlation with the normalised variation of RV stroke volume (ρ = 0.662, p = 0.007) and a borderline moderate positive correlation with the normalised variation of RV end-diastolic indexed volume (ρ = 0.513, p = 0.050). CONCLUSIONS: The assessment of RV LGE before PVR may provide insights on post-PVR functional data, potentially facilitating a patient-tailored treatment pathway.

Human epicardial adipose tissue expresses glucose-dependent insulinotropic polypeptide, glucagon, and glucagon-like peptide-1 receptors as potential targets of pleiotropic therapies.

AIMS: Human epicardial adipose tissue (EAT) plays a crucial role in the development and progression of coronary artery disease, atrial fibrillation, and heart failure. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular, and immune cells. Epicardial adipose tissue is a white adipose tissue, albeit it also has brown fat-like or beige fat-like features. No muscle fascia divides EAT and myocardium; this allows a direct interaction and crosstalk between the epicardial fat and the myocardium. Thus, it might be a therapeutic target for pharmaceutical compounds acting on G-protein-coupled receptors, such as those for glucose-dependent insulinotropic polypeptide (GIP), glucagon (GCG), and glucagon-like peptide-1 (GLP-1), whose selective stimulation with innovative drugs has demonstrated beneficial cardiovascular effects. The precise mechanism of these novel drugs and their tissue and cellular target(s) need to be better understood. We evaluate whether human EAT expresses GIP, GCG, and GLP-1 receptors and whether their presence is related to EAT transcriptome. We also investigated protein expression and cell-type localization specifically for GIP receptor (GIPR) and glucagon receptor (GCGR). METHODS AND RESULTS: Epicardial adipose tissue samples were collected from 33 patients affected by cardiovascular diseases undergoing open heart surgery (90.9% males, age 67.2 ± 10.5 years mean ± SD). Microarray and immunohistochemistry analyses were performed. Microarray analysis showed that GIPR and GCGR messenger ribonucleic acids (mRNAs) are expressed in EAT, beyond confirming the previously found GLP-1 [3776 ± 1377 arbitrary unit (A.U.), 17.77 ± 14.91 A.U., and 3.41 ± 2.27 A.U., respectively]. The immunohistochemical analysis consistently indicates that GIPR and GCGR are expressed in EAT, mainly in macrophages, isolated, and in crown-like structures. In contrast, only some mature adipocytes of different sizes showed cytoplasmic immunostaining, similar to endothelial cells and pericytes in the capillaries and pre-capillary vascular structures. Notably, EAT GIPR is statistically associated with the low expression of genes involved in free fatty acid (FFA) oxidation and transport and those promoting FFA biosynthesis and adipogenesis (P < 0.01). Epicardial adipose tissue GCGR, in turn, is related to genes involved in FFA transport, mitochondrial fatty acid oxidation, and white-to-brown adipocyte differentiation, in addition to genes involved in the reduction of fatty acid biosynthesis and adipogenesis (P < 0.01). CONCLUSIONS: Having reported the expression of the GLP-1 receptor previously, here, we showed that GIPR and GCGR similarly present at mRNA and protein levels in human EAT, particularly in macrophages and partially adipocytes, suggesting these G-protein-coupled receptors as pharmacological targets on the ongoing innovative drugs, which seem cardiometabolically healthy well beyond their effects on glucose and body weight.

Human epicardial adipose tissue (EAT) is a unique and multifunctional fat compartment of the heart. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular, and immune cells. Epicardial adipose tissue is a white adipose tissue, albeit it also has brown fat-like or beige fat-like features. No muscle fascia divides EAT and myocardium; this allows a direct interaction and crosstalk between the epicardial fat and the myocardium. Due to its distinctive transcriptome and functional proximity to the heart, EAT can play a key role in the development and progression of coronary artery disease, atrial fibrillation, and heart failure. Clinically, EAT, given its rapid metabolism and simple measurability, can be considered a novel therapeutic target, owing to its responsiveness to drugs with pleiotropic and clear beneficial cardiovascular effects such as the glucagon-like peptide-1 receptor (GLP-1R) agonists.Human EAT is found to express the genes encoding the receptors of glucose-dependent insulinotropic polypeptide receptor (GIPR), glucagon receptor (GCGR), and GLP-1. The immunohistochemistry indicates that GIP and GCG receptor proteins are present in EAT samples. Epicardial adipose tissue GIPR is inversely associated with genes involved in free fatty acid (FFA) oxidation and transport and with genes promoting FFA biosynthesis and adipogenesis. Epicardial adipose tissue GCGR is correlated with genes promoting FFA transport and activation for mitochondrial beta-oxidation and white-to-brown adipocyte differentiation and with genes reducing FFA biosynthesis and adipogenesis.As the myocardium relies mostly on FFAs as fuel and is in direct contiguity with EAT, these findings may have a great importance for the modulation of the myocardial activity and performance. Given the emerging use and cardiovascular effects of GLP-1R agonists, dual GIPR/GLP-1R agonists, and GLP-1R/GIPR/GCGR triagonists, we believe that pharmacologically targeting and potentially modulating organ-specific fat depots through G-protein­coupled receptors may produce beneficial cardiovascular and metabolic effects.

Psoas Cross-Sectional Measurements Using Manual CT Segmentation before and after Endovascular Aortic Repair (EVAR).

Sarcopenia has been associated with an increased incidence of adverse outcomes, including higher mortality, after endovascular aortic repair (EVAR). We aim to use computed tomography (CT) to quantify changes in total psoas muscles area (PMA) and psoas muscle density (PMD) after EVAR, and to evaluate the reproducibility of both measurements. PMA and PMD were assessed via manual segmentation of the psoas muscle on pre- and post-operative CT scans belonging to consecutive patients who underwent EVAR. Wilcoxon test was used to compare PMA and PMD before and after EVAR, and inter- and intra-reader agreements of both methods were evaluated through Bland−Altman analysis. A total of 50 patients, 42 of them males (84%), were included in the study. PMA changes from 1243 mm2 (1006−1445 mm2) to 1102 mm2 (IQR 937−1331 mm2), after EVAR (p < 0.001). PMD did not vary between pre-EVAR (33 HU, IQR 26.5−38.7 HU) and post-EVAR (32 HU, IQR 26−37 HU, p = 0.630). At inter-reader Bland−Altman analysis, PMA showed a bias of 64.0 mm2 and a coefficient of repeatability (CoR) of 359.2 mm2, whereas PMD showed a bias of −2.43 HU and a CoR of 6.19 HU. At intra-reader Bland−Altman analysis, PMA showed a bias of −81.1 mm2 and a CoR of 394.6 mm2, whereas PMD showed a bias of 1.41 HU and a CoR of 6.36 HU. In conclusion, PMA decreases after EVAR. A good intra and inter-reader reproducibility was observed for both PMA and PMD. We thus propose to use PMA during the follow-up of patients who underwent EVAR to monitor muscle depletion after surgery.

Quantification of epicardial adipose tissue in obese patients using an open-bore MR scanner.

BACKGROUND: Our aim was to evaluate the reproducibility of epicardial adipose tissue (EAT) volume, measured on scans performed using an open-bore magnetic resonance scanner. METHODS: Consecutive patients referred for bariatric surgery, aged between 18 and 65 years who agreed to undergo cardiac imaging (MRI), were prospectively enrolled. All those with cardiac pathology or contraindications to MRI were excluded. MRI was performed on a 1.0-T open-bore scanner, and EAT was segmented on all scans at both systolic and diastolic phase by two independent readers (R1 with four years of experience and R2 with one year). Data were reported as median and interquartile range; agreement and differences were appraised with Bland-Altman analyses and Wilcoxon tests, respectively. RESULTS: Fourteen patients, 11 females (79%) aged 44 (41-50) years, underwent cardiac MRI. For the first and second readings, respectively, EAT volume was 86 (78-95) cm3 and 85 (79-91) cm3 at systole and 82 (74-95) cm3 and 81 (75-94) cm3 at diastole for R1, and 89 (79-99) cm3 and 93 (84-98) cm3 at systole and 92 (85-103) cm3 and 93 (82-94) cm3 at diastole for R2. R1 had the best reproducibility at diastole (bias 0.3 cm3, standard deviation of the differences (SD) 3.3 cm3). R2 had the worst reproducibility at diastole (bias 3.9 cm3, SD 12.1 cm3). The only significant difference between systole and diastole was at the first reading by R1 (p = 0.016). The greatest bias was that of inter-reader reproducibility at diastole (-9.4 cm3). CONCLUSIONS: Reproducibility was within clinically acceptable limits in most instances.

Dysphagia aortica.

Background: Dysphagia aortica is an umbrella term to describe swallowing obstruction from external aortic compression secondary to a dilated, tortuous, or aneurysmal aorta. We performed a systematic literature review to clarify clinical features and outcomes of patients with dysphagia aortica. Materials and methods: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library. The terms "aortic dysphagia," "dysphagia aortica," "dysphagia AND aortic aneurysm" were matched. We also queried the prospectively updated database of our esophageal center to identify patients with aortic dysphagia referred for diagnosis and treatment over the past two decades. Results: A total of 57 studies including 69 patients diagnosed with dysphagia aortica were identified, and one patient from our center was added to the database. The mean age was 72 years (range 22-98), and the male to female ratio 1.1:1. Of these 70 patients, the majority (n = 63, 90%) had an aortic aneurysm, pseudoaneurysm, or dissection. Overall, 37 (53%) patients received an operative treatment (81.1% a vascular procedure, 13.5% a digestive tract procedure, 5.4% both procedures). Thoracic endovascular aortic repair (TEVAR) accounted for 60% of all vascular procedures. The postoperative mortality rate was 21.2% (n = 7/33). The mortality rate among patients treated conservatively was 55% (n = 11/20). Twenty-six (45.6%) studies were deemed at a high risk of bias. Conclusion: Dysphagia aortica is a rare clinical entity with high morbidity and mortality rates and no standardized management. Early recognition of dysphagia and a high suspicion of aortoesophageal fistula may be lifesaving in this patient population.

Potential role of epicardial adipose tissue as a biomarker of anthracycline cardiotoxicity.

BACKGROUND: We investigated the radiodensity of epicardial (EAT), subcutaneous (SAT), and visceral adipose tissue (VAT) before and after treatment with anthracyclines in a population of breast cancer (BC) patients, and in controls not treated with anthracyclines, to detect a potential role of EAT density as a biomarker of changes related to chemotherapy cardiotoxicity. METHODS: We reviewed BC patients treated with anthracyclines who underwent CT before (CT-t0) and after (CT-t1) chemotherapy, and age- and sex-matched controls who underwent two CT examinations at comparable intervals. On non-contrast scans, EAT was segmented contouring the pericardium and thresholding between -190 and -30 Hounsfield units (HU), and SAT and VAT were segmented with two 15-mm diameter regions of interest thresholded between -195 and -45 HU. RESULTS: Thirty-two female patients and 32 controls were included. There were no differences in age (p = 0.439) and follow-up duration (p = 0.162) between patients and controls. Between CT-t0 and CT-t1, EAT density decreased in BC patients (-66 HU, interquartile range [IQR] -71 to -63 HU, to -71 HU, IQR -75 to -66 HU, p = 0.003), while it did not vary in controls (p = 0.955). SAT density increased from CT-t0 to CT-t1 in BC patients (-107 HU, IQR -111 to -105 HU, to -105 HU, IQR -110 to -100 HU, p = 0.014), whereas it did not change in controls (p = 0.477). VAT density did not vary in either BC patients (p = 0.911) or controls (p = 0.627). CONCLUSIONS: EAT density appears to be influenced by anthracycline treatment for BC, well known for its cardiotoxicity, shifting towards lower values indicative of a less active metabolism.

Appropriate use criteria for cardiovascular magnetic resonance imaging (CMR): SIC-SIRM position paper part 1 (ischemic and congenital heart diseases, cardio-oncology, cardiac masses and heart transplant).

Cardiac magnetic resonance (CMR) has emerged as new mainstream technique for the evaluation of patients with cardiac diseases, providing unique information to support clinical decision-making. This document has been developed by a joined group of experts of the Italian Society of Cardiology and Italian society of Radiology and aims to produce an updated consensus statement about the current state of technology and clinical applications of CMR. 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 radiology. Part 1 of the document will cover ischemic heart disease, congenital heart disease, cardio-oncology, cardiac masses and heart transplant.

Poor concordance between definitions of type III arch and implications for risk prediction and assessment for carotid artery stenting.

OBJECTIVE: The type III arch configuration has been inconsistently reported as a stroke risk factor during carotid artery stenting. However, at least three different methods for the definition of type III arch can be identified in the literature, related to the level of the origin of the innominate artery (IA). According to Casserly's definition, a type III arch presents with an origin of the IA below the horizontal plane of the inner curvature. According to Madhwal's definition, a type III arch has a distance greater than twice the diameter of the left common carotid artery between the highest point of the arch and the origin of the IA. According to MacDonald's definition, a type III arch presents with a distance of ≥2 cm between the highest point of the arch and the origin of the IA. Our aim was to assess the level of concordance between these different methods. METHODS: Anonymized thoracic computed tomography scans of 100 healthy patients were reviewed. Two of us independently stratified the selected cases as a type I to III arch, according to the three considered definitions. The interobserver level of concordance for each type III arch classification and level of concordance among the three definitions were assessed. RESULTS: The 100 selected patients (64% male) were 76 ± 7 years old. For each definition, the interobserver repeatability was almost perfect for all three (Madhwal, κ = 0.81; 95% confidence interval [CI], 0.71-0.99; MacDonald, κ = 0.82; 95% CI, 0.72-0.92; Casserly, κ = 0.84; 95% CI, 0.74-0.93). The level of concordance among the different definitions was very low (Madhwal vs MacDonald, 85% [P = .002]; 33% for type III arch; Madhwal vs Casserly, 60% [P < .0001]; 12% for type III arch; MacDonald vs Casserly, 75% [P < .0001]; 12% for type III arch). CONCLUSIONS: The three definitions of the type III arch have a very low level of concordance, which might account for the varying clinical relevance of this configuration. Our findings have relevant implications for risk prediction for carotid artery stenting based on the presence of a type III arch, for comparisons of the results from different studies, and for comparisons of different datasets from multicenter trials.

Computed tomography-derived myocardial extracellular volume: an early biomarker of cardiotoxicity in esophageal cancer patients undergoing radiation therapy.

OBJECTIVES: We aimed to assess extracellular volume (ECV) through non-gated, contrast-enhanced computed tomography (CT) before and after radiation therapy (RT) in patients with esophageal cancer (EC). MATERIALS AND METHODS: EC patients who had undergone CT before and after RT were retrospectively assessed. Patients with preexisting cardiovascular disease or with heavily artifacted CT were excluded. ECV was calculated using density values for the myocardial septum and blood pool. Data were reported as mean and standard deviation or median and interquartile range according to their distribution; t test or Wilcoxon and Pearson r or Spearman ρ were subsequently used. RESULTS: Twenty-one patients with stage ≥ IB EC, aged 64 ± 18 years, were included. Mean and maximum RT doses were 21.2 Gy (16.9-24.1) and 42.5 Gy (41.8-49.2), respectively. At baseline (n = 21), hematocrit was 39% ± 4%, ECV 27.9% ± 3.5%; 35 days (30-38) after RT (n = 20), hematocrit was 36% ± 4%, lower than at baseline (p = 0.002), ECV 30.3% ± 8.3%, higher than at baseline (p = 0.081); at follow-up 420 days (244-624) after RT (n = 13), hematocrit was 36% ± 5%, lower than at baseline (p = 0.030), ECV 31.4% ± 4.5%, higher than at baseline (p = 0.011). No patients showed signs of overt cardiotoxicity. ECV early after RT was moderately positively correlated with maximum RT dose (ρ = 0.50, p = 0.036). CONCLUSIONS: In EC patients, CT-derived myocardial ECV was increased after RT and may thus appear as a potential early biomarker of cardiotoxicity.

Anomalous aortic origin of coronary artery biomechanical modeling: Toward clinical application.

OBJECTIVES: Anomalous aortic origin of the coronary artery can be associated with sudden cardiac death and ischemic events. Anatomic static characteristics mainly dictated surgical indications, although adverse events are usually related to dynamic physical effort. We developed a computational model able to simulate anomalous coronary behavior, and we aimed to assess its clinical applicability and to investigate coronary characteristics at increasing loading stress conditions. METHODS: We selected 5 patients with anomalous aortic origin of the coronary artery and 5 control subjects. For each of them, we construct a 3-dimensional model resembling the aortic root and coronary arteries based on 25 parameters obtained from computed tomography. Structural finite element analysis simulations were run to simulate pressure increasing in the aortic root during exercise (+40 mm Hg, +100 mm Hg with respect baseline condition, assumed at 80 mm Hg) and investigate coronary lumen characteristics. RESULTS: The 25 parameters were obtainable in all subjects with a consistent interobserver agreement. In control subjects, the right coronary artery had a more significant lumen expansion at loading conditions compared with anomalous aortic origin of coronary artery (6%-19.2% vs 1.8%-8.1%, P = .008), which also showed an inability to expand within the intramural segment. CONCLUSIONS: The proposed anomalous aortic origin of coronary artery model is able to represent the pathogenic disease mechanism after being populated with patient-specific data. It can assess the impaired expansion of anomalous right coronary at loading conditions, a process that cannot be quantified in any clinical set-up. This first clinical application showed promising results on quantifying pathological behavior, potentially helping in patient-specific risk stratification.

Assessment of myocardial extracellular volume on body computed tomography in breast cancer patients treated with anthracyclines.

BACKGROUND: Cancer treatment with anthracyclines may lead to an increased incidence of cardiac disease due to cardiotoxicity, as they may cause irreversible myocardial fibrosis. So far, the proposed methods for screening patients for cardiotoxicity have led to only limited success, while the analysis of myocardial extracellular volume (mECV) at cardiac magnetic resonance (CMR) has shown promising results, albeit requiring a dedicated exam. Recent studies have found strong correlations between mECV values obtained through computed tomography (CT), and those derived from CMR. Thus, our purpose was to evaluate the feasibility of estimating mECV on thoracic contrast-enhanced CT performed for staging or follow-up in breast cancer patients treated with anthracyclines, and, if feasible, to assess if a rise in mECV is associated with chemotherapy, and persistent over time. METHODS: After ethics committee approval, female patients with breast cancer who had undergone at least 2 staging or follow-up CT examinations at our institution, one before and one shortly after the end of chemotherapy including anthracyclines were retrospectively evaluated. Patients without available haematocrit, with artefacts in CT images, or who had undergone radiation therapy of the left breast were excluded. Follow-up CT examinations at longer time intervals were also analysed, when available. mECV was calculated on scans obtained at 1, and 7 min after contrast injection. RESULTS: Thirty-two female patients (aged 57±13 years) with pre-treatment haematocrit 38%±4%, and ejection fraction 64%±6% were analysed. Pre-treatment mECV was 27.0%±2.9% at 1 min, and 26.4%±3.8% at 7 min, similar to values reported for normal subjects in the literature. Post-treatment mECV (median interval: 89 days after treatment) was 31.1%±4.9%, and 30.0%±5.1%, respectively, values significantly higher than pre-treatment values at all times (P<0.005). mECV at follow-up (median interval: 135 days after post-treatment CT) was 31.0%±4.5%, and 27.7%±3.7%, respectively, without significant differences (P>0.548) when compared to post-treatment values. CONCLUSIONS: mECV values from contrast-enhanced CT scans could play a role in the assessment of myocardial condition in breast cancer patients undergoing anthracycline-based chemotherapy. CT-derived ECV could be an imaging biomarker for the monitoring of therapy-related cardiotoxicity, allowing for potential secondary prevention of cardiac damage, using data derived from an examination that could be already part of patients' clinical workflow.

Type III Arch Configuration as a Risk Factor for Carotid Artery Stenting: A Systematic Review of Contemporary Guidelines on Management of Carotid Artery Stenosis.

BACKGROUND: Type III arch configuration is frequently reported as a stroke risk factor for carotid angioplasty and stenting (CAS). We reviewed contemporary guidelines on management of carotid artery stenosis to assess the clinical relevance attributed to this anatomic feature in current clinical practice. METHODS: The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The PubMed, EMBASE, and Web of Science databases were searched to identify all guidelines on extracranial carotid disease published between January 2008 and March 2020. A total of 435 articles were screened. For multiple guidelines from the same writing group, only the most recent updated version was considered. Eighteen documents were identified for qualitative analysis. RESULTS: Four guidelines specifically reported type III arch as a predictive factor of periprocedural complications after CAS. Two of them also provided a low level of evidence of their recommendation. None of the documents indicated the exact criteria for aortic arch classification. Three different methods to describe type III arch configuration were identified. CONCLUSIONS: Type III arch configuration is inconsistently included among stroke risk factors for CAS in contemporary guidelines, and variably defined. Further studies on the level of concordance between the 3 existing definition criteria are warranted.

Geometric Pattern of Proximal Landing Zones for Thoracic Endovascular Aortic Repair in the Bovine Arch Variant.

OBJECTIVE: The aim was to investigate whether the "bovine" aortic arch (i.e. arch variant with a common origin of the innominate and left carotid artery (CILCA)) is associated with a consistent geometric configuration of proximal landing zones for thoracic endovascular aortic repair (TEVAR). METHODS: Anonymised thoracic computed tomography (CT) scans of healthy aortas were reviewed to retrieve 100 cases of CILCA. Suitable cases were stratified according to type 1 and 2 CILCA, and also based on type of arch (I, II, and III). Further processing allowed calculation of angulation and tortuosity of the proximal landing zones. Centre lumen line lengths of each proximal landing zone were measured in a view perpendicular to the centre line. All geometric features were compared with those measured in healthy patients with a standard arch configuration (n = 60). Two senior authors independently evaluated the CT scans, and intra- and interobserver repeatability were assessed. RESULTS: The 100 selected patients (63% male) were 71.4 ± 7.7 years old. Type 1 CILCA (62/100) was more prevalent than type 2 CILCA (38/100), and the two groups were comparable in age (p = .11). Zone 3 presented a severe angulation (i.e. > 60°), which was greater than in Zone 2 (p < .001), and a consistently greater tortuosity than Zone 2 (p = .003). This pattern did not differ between type 1 and type 2 CILCA. A greater tortuosity was also observed in Zone 0, which was related to increased elongation of the ascending aorta (i.e. Zone 0), than the standard configuration. The CILCA had an overall greater elongation, and Zone 2 also was specifically longer. When stratifying by type of arch, reversely from Type III to Type I, the CILCA presented a gradual flattening of its transverse tract, which entailed a consistent progressive elongation (p = .03) and kinking of the ascending aorta, with a significant increase of Zone 0 angulation to even a severe degree (p = .001). Also, from Type III to Type I, Zone 2 presented a progressively shorter length (p = .004), which was associated with increased tortuosity (p < .05). Mean intra- and interobserver differences for angulation measurements were 1.4° ± 6.8° (p = .17) and 2.0° ± 10.1° (p = .19), respectively. CONCLUSION: CILCA presents a consistent and peculiar geometric pattern compared with standard arch configuration, which provides relevant information for TEVAR planning, and may have prognostic implications.

Aortic arch variant with a common origin of the innominate and left carotid artery as a determinant of thoracic aortic disease: a systematic review and meta-analysis.

The aim of this study was to investigate whether the 'bovine' arch [i.e. arch variant with a common origin of the innominate and left carotid artery (CILCA)] is associated with an increased risk of thoracic aortic disease (TAD). The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed, EMBASE and Cochrane databases were searched to identify all case series reporting about CILCA arch and TAD between January 2008 and December 2018. A total of 485 studies were screened. The prevalence of CILCA arch was assessed, and data analysis was performed considering the difference in the risk of TAD for presence versus absence of CILCA arch. Eight studies enrolling 11 381 subjects were retrieved for quantitative analysis. The proportion of TAD among CILCA arch patients was higher [41.5% (28.1-56.4)] than the proportion among patients with standard arch configuration 34.0% (20.1-51.4). The odds ratio of developing TAD was 1.4 times higher in subjects with CILCA arch (95% confidence interval 1.068-1.839). The test for an overall effect indicated a significant association between CILCA arch and TAD (P < 0.015). The I2 was 78.1% with a value of P < 0.001 for heterogeneity. The Egger test did not show evidence of publication bias (P = 0.317). In conclusion, our meta-analysis supports the hypothesis of a correlation between the presence of CILCA arch and the onset of TAD. Our results warrant a specific and long-term surveillance for patients with this anatomical variant, and a thorough awareness of its potential clinical implications during image interpretation.

Prevalence of type III arch configuration in patients with type B aortic dissection.

OBJECTIVES: Type III aortic arch configuration consistently presents anatomical and biomechanical characteristics which have been associated with an increased risk of type B aortic dissection (TBD). Our aim was to investigate the prevalence of type III arch in patients with TBD and type B intramural haematoma (IMH-B). METHODS: A multicentre retrospective analysis was performed on patients with TBD and IMH-B observed between 2002 and 2017. The computed tomographic images were reviewed to identify the type of aortic arch. Exclusion criteria included previous arch surgery, presence of aortic dissection or aneurysm proximal to the left subclavian artery and bovine arches. An ad hoc systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to assess the prevalence of type III arch in non-TBD and non-aneurysmal patients. RESULTS: Two hundred and sixty-one patients with TBD/IMH-B were found to be suitable for the study and were stratified according to aortic arch classification. The ad hoc literature search provided 10 relevant articles, from which a total of 7983 control cases were retrieved. TBD/IMH-B patients were significantly younger than controls [64.3, standard error: 0.74 (62.84-65.76) vs mean pooled age 70.5, standard error: 0.40 (69.71-71.28)]. Patients with TBD/IMH-B presented with a significantly higher prevalence of type III arch [41.0% (107/261) (35.2-47.1)] than controls [16% (1241/7983) (10-22)]. CONCLUSIONS: Our data indicate an association between type III arch configuration and the occurrence of TBD/IMH-B. These findings warrant further studies to disclose the potential role of type III arch configuration as an anatomical risk factor for TBD/IMH-B.

The Modified Arch Landing Areas Nomenclature identifies hostile zones for endograft deployment: a confirmatory biomechanical study in patients treated by thoracic endovascular aortic repair†.

OBJECTIVES: Our goal was to confirm whether the Modified Arch Landing Areas Nomenclature (MALAN) for thoracic endovascular aortic repair, in which each landing area is described by indicating both the proximal landing zone (PLZ) and the type of arch (e.g. 0/I), identifies unfavourable landing zones for endograft deployment in diseased aortas. METHODS: Preoperative computed tomography angiography scans of 10 patients scheduled for thoracic endovascular aortic repair for aneurysm or penetrating ulcer of the arch and with a potential hostile PLZ were reviewed. Five had proximal deployment planned in MALAN area 3/III and 5, in MALAN area 2/III. The angulation of each PLZ was calculated. Computational fluid dynamics modelling was used to compute magnitude and orientation of pulsatile displacement forces in each PLZ. Normalized values based on PLZ areas (i.e. equivalent surface traction) were calculated. Results were compared to those obtained in healthy controls stratified by the MALAN. RESULTS: Angulation was severe (>60°) in MALAN areas 3/III and 2/III, which was consistent with the findings obtained in healthy controls. Increased magnitude (P = 0.021) and unfavourable orientation (i.e. orthogonal to the longitudinal aortic axis) of equivalent surface traction (P = 0.011) was also found in these areas compared to the adjacent ones, following the same pattern seen in the controls. Adverse events related to proximal endograft performance were reported in 3/10 cases. CONCLUSIONS: This study confirms in diseased aortas initial proof-of-concept findings on the predictive value of the MALAN to identify landing areas with a geometric and haemodynamic environment hostile for thoracic endovascular aortic repair. These adverse biomechanical features may entail an increased risk of dismal endograft performance.