The Use of Radiomic Analysis in Cardiovascular Diseases.

A The recent years of the cardiovascular medicine saw a rapid development of advanced imaging modalities. The new era of personalized medicine takes advantage of what can be interpreted from medical images, searching for underlying connections between image phenotyping and biological characteristics to support precise clinical decisions. The application of radiomics in cardiovascular imaging has lagged behind other fields, such as oncology. While the current interpretation of cardiac and vascular images mainly depends on subjective and qualitative analysis, radiomics uses advanced image analysis to extract numerous quantitative features from digital images that are unrecognizable to the naked eye. The goal of this narrative review is to highlight the main findings of the recent use of radiomic analysis in the cardiovascular field. English-language articles published in the database PubMed were used for this review. The keywords used in the search included radiomics, cardiovascular or cardiac or aortic. Radiomics is expected to contribute to a more precise phenotyping of the cardiovascular disease, which can improve diagnostic, prognostic, and therapeutic decision making in the near future.

Cancer- and cardiac-induced cachexia: same fate through different inflammatory mediators?

BACKGROUND: Inflammation is widely recognized as the driving force of cachexia induced by chronic diseases; however, therapies targeting inflammation do not always reverse cachexia. Thus, whether inflammation per se plays an important role in the clinical course of cachectic patients is still a matter of debate. AIMS: To give new insights into cachexia's pathogenesis and diagnosis, we performed a comprehensive literature search on the contribution of inflammatory markers to this syndrome, focusing on the noncommunicable diseases cancer and cardiovascular diseases. METHODS: A systematic review was performed in PubMed using the keywords ("cancer" OR "cardiac" cachexia AND "human" OR "patient" AND "plasma" or "serum"). A total of 744 studies were retrieved and, from these, 206 were selected for full-text screening. In the end, 98 papers focusing on circulating biomarkers of cachexia were identified, which resulted in a list of 113 different mediators. RESULTS: Data collected from the literature highlight the contribution of interleukin-6 (IL-6) and C-reactive protein (CRP) to cachexia, independently of the underlying condition. Despite not being specific, once the diagnosis of cachexia is established, CRP might help to monitor the effectiveness of anti-cachexia therapies. In cardiac diseases, B-type natriuretic peptide (BNP), renin, and obestatin might be putative markers of body wasting, whereas in cancer, growth differentiation factor (GDF) 15, transforming growth factor (TGF)-ß1 and vascular endothelial growth factor (VEGF) C seem to be better markers of this syndrome. Independently of the circulating mediators, NF-κB and JAK/STAT signaling pathways play a key role in bridging inflammation with muscle wasting; however, therapies targeting these pathways were not proven effective for all cachectic patients. CONCLUSION: The critical and integrative analysis performed herein will certainly feed future research focused on the better comprehension of cachexia pathogenesis toward the improvement of its diagnosis and the development of personalized therapies targeting specific cachexia phenotypes.

Decoding the radiomic and proteomic phenotype of epicardial adipose tissue associated with adverse left atrial remodelling and post-operative atrial fibrillation in aortic stenosis.

AIMS: Epicardial adipose tissue (EAT) volume and attenuation on computed tomography (CT) have been associated with atrial fibrillation. Beyond these conventional CT measures, radiomics allows extraction of high-dimensional data and deep quantitative adipose tissue phenotyping, which may capture its underlying biology. We aimed to explore the EAT proteomic and CT-radiomic signatures associated with impaired left atrial (LA) remodelling and post-operative atrial fibrillation (POAF). METHODS AND RESULTS: We prospectively included 132 patients with severe aortic stenosis with no prior atrial fibrillation referred for aortic valve replacement. Pre-operative non-contrast CT images were obtained for extraction of EAT volume and other radiomic features describing EAT texture. The LA function was assessed by 2D-speckle-tracking echocardiography peak atrial longitudinal strain and peak atrial contraction strain. The EAT biopsies were performed during surgery for proteomic analysis by sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS). The POAF incidence was monitored from surgery until discharge. Impaired LA function and incident POAF were associated with EAT up-regulation of inflammatory and thrombotic proteins, and down-regulation of cardioprotective proteins with anti-inflammatory and anti-lipotoxic properties. The EAT volume was independently associated with LA enlargement, impaired function, and POAF risk. On CT images, EAT texture of patients with POAF was heterogeneous and exhibited higher maximum grey-level values than sinus rhythm patients, which correlated with up-regulation of inflammatory and down-regulation of lipid droplet-formation EAT proteins. The CT radiomics of EAT provided an area under the curve of 0.80 (95% confidence interval: 0.68-0.92) for discrimination between patients with POAF and sinus rhythm. CONCLUSION: Pre-operative CT-radiomic profile of EAT detected adverse EAT proteomics and identified patients at risk of developing POAF.

A Pleasant Surprise in the Face of ST-Segment Elevation.

ST-segment elevation is a dreadful finding in the emergency department because it is often associated with myocardial infarction and demands a prompt and definitive treatment. However, the clinical and echocardiographic assessment of a patient with electrocardiographic changes trumps any electrocardiology expert and should always lead to a clinical decision. (Level of Difficulty: Intermediate.).

Effects of chronic moderate alcohol consumption on right ventricle and pulmonary remodelling.

NEW FINDINGS: What is the central question of this study? Does the consumption of a moderate amount of alcohol differentially impact the heart ventricles and pulmonary vasculature. What is the main finding and its importance? Moderate alcohol consumption for a short period of time impaired pulmonary vascular cellular renewal through an apoptosis resistance pattern that ultimately affected the right ventricular function and structure. These findings support the need for a deeper understanding of effects of moderate alcohol consumption on the overall cardiovascular and pulmonary systems. ABSTRACT: Over the past decades, observational studies have supported an association between moderate alcohol consumption and a lower risk of cardiovascular disease and mortality. However, recent and more robust meta-analyses have raised concerns around the robustness of the evidence for the cardioprotective effects of alcohol. Also, studies of the functional, structural and molecular changes promoted by alcohol have focused primarily on the left ventricle, ignoring the fact that the right ventricle could adapt differently. The aim of this study was to evaluate the bi-ventricular impact of daily moderate alcohol intake, during a 4-week period, in a rodent model. Male Wistar rats were allowed to drink water (Control) or a 5.2% ethanol mixture (ETOH) for 4 weeks. At the end of the protocol bi-ventricular haemodynamic recordings were performed and samples collected for further histological and molecular analysis. ETOH ingestion did not impact cardiac function. However, it caused right ventricle hypertrophy, paralleled by an activation of molecular pathways responsible for cell growth (ERK1/2, AKT), proteolysis (MURF-1) and oxidative stress (NOX4, SOD2). Furthermore, ETOH animals also presented remodelling of the pulmonary vasculature with an increase in pulmonary arteries' medial thickness, which was characterized by increased expression of apoptosis-related proteins expression (BCL-XL, BAX and caspases). Moderate alcohol consumption for a short period of time impaired the lungs and the right ventricle early, before any change could be detected on the left ventricle. Right ventricular changes might be secondary to alcohol-induced pulmonary vasculature remodelling.

Abdominal aortic aneurysm calcification: trying to identify a reliable semiquantitative method.

BACKGROUND: The main objective of this study was to assess the correlation between three semiquantitative and one computerized method based on Agatston Score (AS), when measuring abdominal aortic calcification (AAC) in abdominal aortic aneurysm (AAA) patients. Secondary aim was to access differences in AAC upon clinical variables, when different methods of calcium scoring are used. METHODS: This was an observational, retrospective, cross-sectional study. A database of AAA patients consecutively submitted to elective repair between 2008 and 2015 was used. Patients were excluded if they did not have preoperative imaging or presented scans incompatible with at least one of the whole set of calcification methods tested. Calcification measures were performed using AS, Aortic Calcification Index (ACI), AAC-8 and AAC-24 methods. The Pearson's correlation was used for primary analysis. RESULTS: Study population comprised 102 patients, 95% males, with a median age of 71 (interquartile range, IQR 66-76) years. AAAs presented median aortic diameter of 60 (54-70) mm. Pearson's correlation with AS was 0.816 for ACI, 0.703 for AAC-8 and 0.648 for AAC-24. ACI also presented the highest ICC for intraobserver agreement (0.972) and for interobserver agreement (0.966). ACI was associated more often to demographic and clinical variables in the dataset that associated with the computerized method. CONCLUSIONS: ACI is suggested as a fast and easy-to-use method of assessing AAC in AAA patients. Its use should be encouraged to study AAC in AAA over other semiquantitative methods, in research settings.

Impact of Gradual Adoption of EVAR in Elective Repair of Abdominal Aortic Aneurysm: A Retrospective Cohort Study from 2009 to 2015.

INTRODUCTION: The recommendations about the preferred type of elective repair of abdominal aortic aneurysm (AAA) still divides guidelines committees, even nowadays. The aim is to assess outcomes after AAA repair focusing on differences between endovascular aneurysm repair (EVAR) and open surgical repair (OSR). METHODS: The observational retrospective cohort study of consecutive patients submitted to elective AAA repair at a tertiary center, 2009-2015. Exclusion criteria were as follows: nonelective cases or complex aortic aneurysms. Primary outcomes were postoperative complications, length of hospital stay, survival, freedom from aortic-related mortality, and vascular reintervention. Time trends were assessed along the period under analysis. RESULTS: From a total of 211 included patients, those submitted to EVAR were older (74 ± 7 vs. 67 ± 9 years; P < 0.001), presented a higher prevalence of hypertension (83.5% vs. 68.5%, P = 0.004), obesity (28.7% vs. 14.3%, P = 0.029), previous cardiac revascularization (30.5% vs. 14.7%, P = 0.005), heart failure (17.2% vs. 5.2%, P = 0.013), and chronic obstructive pulmonary disease (32.8% vs. 13.3%, P = 0.002). Patients were followed during a median of 49 months. EVAR resulted in a significantly shorter length of hospital stay (median 4 and interquartile range 3 vs. 8 (9); P < 0.001), lower 30-day complications (10.6% vs. 22.8%, P = 0.017), lower aortic-related mortality, and similar reintervention after adjustment with a propensity score. Along the time under analysis, EVAR became the predominate type of repair (P = 0.024), the proportion of complications decreased (P = 0.014), and the 30-day mortality (P = 0.035). CONCLUSIONS: Although EVAR was offered to patients with more comorbidities, better and durable outcomes were achieved after EVAR, favoring its adoption for elective AAA repair.

Anti-Remodeling Effects of Xanthohumol-Fortified Beer in Pulmonary Arterial Hypertension Mediated by ERK and AKT Inhibition.

Polyphenols present in some alcoholic beverages have been linked to beneficial effects in preventing cardiovascular diseases. Polyphenols found in beer with anti-proliferative and anti-cancer properties are appealing in the context of the quasi-malignant phenotype of pulmonary arterial hypertension (PAH). Our purpose was to evaluate if the chronic ingestion of a xanthohumol-fortified beer (FB) would be able to modulate the pathophysiology of experimental PAH. Male Wistar rats with monocrotaline (MCT)-induced PAH (60 mg/kg) were allowed to drink either xanthohumol-fortified beer (MCT + FB) or 5.2% ethanol (MCT + SHAM) for a period 4 weeks. At the end of the protocol, cardiopulmonary exercise testing and hemodynamic recordings were performed, followed by sample collection for further analysis. FB intake resulted in a significant attenuation of the pulmonary vascular remodeling in MCT + FB animals. This improvement was paralleled with the downregulation in expression of proteins responsible for proliferation (ERK1/2), cell viability (AKT), and apoptosis (BCL-XL). Moreover, MCT + FB animals presented improved right ventricle (RV) function and remodeling accompanied by VEGFR-2 pathway downregulation. The present study demonstrates that a regular consumption of xanthohumol through FB modulates major remodeling pathways activated in experimental PAH.

[Perspectives and research challenges in abdominal aortic aneurysm calcification]. / Perspetivas e desafios do estudo da calcificação no aneurisma da aorta abdominal.

Abdominal aortic aneurysm (AAA) remains a relevant cause of mortality in Western countries. There is a need for continuous identification of risk factors for aneurysmal progression and predictors of treatment response to optimize the therapeutic strategy to be offered to these patients. Vascular calcification has been studied in several capillary beds as a cardiovascular risk factor. However, the importance of abdominal aortic calcification (AC) in AAA remains incompletely clarified, and the available evidence is scattered and heterogeneous. The objective of this review is to describe the possible impact of AC on aneurysmal progression and rupture, as well as on the response to endovascular correction. It should be noted that the establishment of a validated, quick and easy to use method for assessing AC would be of great clinical and/or research utility.

O aneurisma da aorta abdominal (AAA) permanece uma causa relevante de mortalidade nos países ocidentais. É premente a contínua identificação de fatores de risco de progressão aneurismática bem como de preditores de resposta ao tratamento na otimização da estratégia terapêutica a oferecer a estes doentes. A calcificação vascular tem sido estudada em diversos leitos capilares como um fator de prognóstico cardiovascular. Contudo, a importância da calcificação da aorta abdominal (CA) no AAA permanece incompletamente esclarecida, sendo a prova científica disponível dispersa e heterogénea. O objetivo desta revisão é descrever o eventual impacto da CA na progressão e rutura aneurismática, bem como na resposta à correção endovascular do AAA. Salienta-se que o estabelecimento de um método validado, rápido e fácil de usar para avaliar a CA seria de grande utilidade clínica e/ou investigacional.

High Density of Periaortic Adipose Tissue in Abdominal Aortic Aneurysm.

OBJECTIVES: Perivascular adipose tissue (PVAT) is currently seen as a paracrine organ that produces vasoactive substances, including inflammatory agents, which may have an impact on the vasculature. In this study PVAT density was quantified in patients with an aortic aneurysm and compared with those with a non-dilated aorta. Since chronic inflammation, as the pathway to medial thinning, is a hallmark of abdominal aortic aneurysms (AAAs), it was hypothesised that PVAT density is higher in AAA patients. METHODS: In this multicentre retrospective case control study, three groups of patients were included: non-treated asymptomatic AAA (n = 140), aortoiliac occlusive disease (AIOD) (n = 104), and individuals without aortic pathology (n = 97). A Hounsfield units based analysis was performed by computed tomography (CT). As a proxy for PVAT, the density of adipose tissue 10 mm circumferential to the infrarenal aorta was analysed in each consecutive CT slice. Intra-individual PVAT differences were reported as the difference in PVAT density between the region of the maximum AAA diameter (or the mid-aortic region in patients with AIOD or controls) and the two uppermost slices of infrarenal non-dilated aorta just below the renal arteries. Furthermore, subcutaneous (SAT) and visceral (VAT) adipose tissue measurements were performed. Linear models were fitted to assess the association between the study groups, different adipose tissue compartments, and between adipose tissue compartments and aortic dimensions. RESULTS: AAA patients presented higher intra-individual PVAT differences, with higher PVAT density around the aneurysm sac than the healthy neck. This association persisted after adjustment for cardiovascular risk factors and diseases and other fat compartments (ß = 13.175, SE 4.732, p = .006). Furthermore, intra-individual PVAT differences presented the highest correlation with aortic volume that persisted after adjustment for other fat compartments, body mass index, sex, and age (ß = 0.566, 0.200, p = .005). CONCLUSION: The results suggest a relation between the deposition of PVAT and AAA pathophysiology. Further research should explore the exact underlying processes.

Mini-Review on Cachexia-Related miRNA.

Cachexia, or muscle wasting, is a complex metabolic syndrome associated with an underlying illness and characterized by loss of muscle mass. It is a rather prevalent condition, with impacts on patient survival, response to treatment, and quality of life. Treatment options are sparse because of cachexia's multifactorial pathogenesis. Recently, attention has focused on microRNAs (miRNAs) as potential therapeutic targets of several diseases. miRNAs are small, 18- to 25-base-long constructs that regulate gene expression on a post-transcriptional level, selectively activating or repressing elements of specific signaling pathways. In this review, we investigated whether miRNAs play any role in cachexia's biochemical pathways and if miRNA targeting has any significant impact on preclinical models of cachexia.