Association of Left Atrial Stiffness With Risk of Cryptogenic Ischemic Stroke in Young Adults.

Background: Incidence of cryptogenic ischemic stroke (CIS) in young adults is increasing. Early left atrial (LA) myopathy might be 1 of the underlying mechanisms, but this has only been scarcely explored. Objectives: The purpose of this study was to assess the association between increased LA stiffness and CIS in young adults. Methods: In the multicenter SECRETO (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome) study, LA function was analyzed by speckle tracking echocardiography in 150 CIS patients (aged 18-49 years) and 150 age- and sex-matched controls. Minimum and maximum LA volumes, LA reservoir and contractile strain were measured. LA stiffness was calculated by the ratio: mitral peak E-wave velocity divided by mitral annular e' velocity (E/e')/LA reservoir strain and considered increased if ≥0.22. Increased LA volumes, LA stiffness, and/or reduced LA strain indicated LA myopathy. Logistic regression was used to determine the relation between LA stiffness and CIS and the clinical variables associated with LA stiffness. Results: Increased LA stiffness was found in 36% of patients and in 18% of controls (P < 0.001). Increased LA stiffness was associated with a 2.4-fold (95% CI: 1.1-5.3) higher risk of CIS after adjustment for age, sex, comorbidities, and echocardiographic confounders (P = 0.03). In patients, obesity, pre-CIS antihypertensive treatment, older age, and lower LA contractile strain were all related to increased LA stiffness (all P < 0.05). Conclusions: LA myopathy with increased LA stiffness and impaired LA mechanics more than doubles the risk of CIS in patients under the age of 50 years. This provides new insights into the link between LA dysfunction and CIS at young ages. (Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome [SECRETO]; NCT01934725).

Association between heavy alcohol consumption and cryptogenic ischaemic stroke in young adults: a case-control study.

BACKGROUND: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age. METHODS: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS. RESULTS: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women. CONCLUSIONS: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.

Central Obesity is Associated with Increased Left Ventricular Maximal Wall Thickness and Intrathoracic Adipose Tissue Measured with Cardiac Magnetic Resonance.

INTRODUCTION: Central obesity (CO), characterized by an increased waist circumference increases the risk of cardiovascular disease (CVD) and morbidity, yet the underlying mechanisms are not fully understood. CO is often associated with general obesity, hypertension, and abnormal glucose tolerance, confounding the independent contribution of CO to CVD. AIM: We investigated the relationship of CO (without associated disorders) with left ventricular (LV) characteristics and intrathoracic adipose tissue (IAT) by cardiac magnetic resonance. METHODS: LV characteristics, epicardial (EAT), and mediastinal adipose tissue (MAT) were measured from 29 normoglycemic, normotensive males with CO but without general obesity (waist circumference >100 cm, body mass index (BMI) <30 kg/m2) and 18 non-obese male controls. RESULTS: LV maximal wall thickness (LVMWT) and IAT but not LV mass or volumes were increased in CO subjects compared to controls (LVMWT, 12.3±1.2 vs. 10.7±1.5 mm, p < 0.001; EAT, 5.5±3.0 vs. 2.2±2.0 cm2, p = 0.001; MAT, 31.0±12.8 vs. 15.4±10.7 cm2, p < 0.001). The LVMWT was ≥12 mm in 69% of subjects with CO and 22% of controls (p = 0.002). In CO suspects, EAT correlated inversely with LV end-diastolic volume index (r = - 0.403, p = 0.037) and LV stroke volume (SV) (r = - 0.425, p = 0.027). MAT correlated inversely with SV (r = - 0.427, p=0.026) and positively with LVMWT (r = 0.399, p = 0.035). Among CO subjects, the waist-to-hip ratio (WHR) was an independent predictor of LVMWT (B = 22.4, ß = 0.617, p < 0.001). The optimal cut-off with Youden's index for LV hypertrophy was identified at WHR 0.98 (sensitivity 85%, specificity 89%). CONCLUSIONS: CO independent of BMI is associated with LV hypertrophy and intrathoracic adipose tissue contributing to cardiovascular burden.

Repaired coarctation of the aorta does not affect four-dimensional flow metrics in bicuspid aortic valve disease.

OBJECTIVES: The objective of this study was primarily to compare four-dimensional flow magnetic resonance imaging metrics in the ascending aorta (AA) of patients with right-left fusion type bicuspid aortic valve (RL-BAV) and repaired coarctation of the aorta (CoA) to RL-BAV without CoA. Metrics of patients with RL-BAV were also compared to the matched group of patients with common tricuspid aortic valve (TAV). METHODS: Eleven patients with RL-BAV and CoA, 11 patients with RL-BAV without CoA and 22 controls with TAV were investigated. Peak velocity (cm/s), peak flow (ml/s) and flow displacement (%) were analysed at 5 pre-defined AA levels. In addition, regional wall shear stress (WSS, mN/m2), circumferential WSS (WSSc) and axial WSS (WSSa) at all levels were quantified in 6 sectors of the aortic circle. Averaged WSS values on each level (WSSavg, WSSc, avg and WSSa, avg) were calculated as well. RESULTS: Peak velocity at the proximal tubular AA was significantly lower in BAV and CoA group (P = 0.047) compared to BAV without CoA. In addition, the WSSa, avg was found to be higher for the BAV and CoA group at proximal AA respectively (P = 0.040). No other significant differences were found between these groups. BAV group's peak velocity was higher at every level (P < 0.001-0.004) compared to TAV group. Flow displacement was significantly higher for the BAV group at every level (P < 0.001) besides at the most distal level. All averaged WSS values were significantly higher in BAV patients in distal AA (P < 0.001-0.018). CONCLUSIONS: Repaired CoA does not relevantly alter four-dimensional flow metrics in the AA of patients with RL-BAV. However, RL-BAV majorly alters flow dynamics in the AA when compared to patients with TAV. CLINICAL TRIAL REGISTRATION NUMBER: https://www.clinicaltrials.gov/study/NCT05065996, Unique Protocol ID 5063566.

Twenty years' experience of type B aortic dissections: a population-based national registry study from Finland.

OBJECTIVES: The objective of this study was to investigate the incidence, treatment and survival of Stanford type B aortic dissection (BTAD) during 20 years in the Finnish population. METHODS: Data collection was made from the Nationwide Care Register for Health Care, Finnish National Institute for Health and Welfare. All patients over 15 years of age with BTAD from 2000 to 2019 were included in the study. A data search of the Registry of Death Cause (Statistic Finland) was carried out to identify the date and cause of death. RESULTS: There were 1742 cases of BTAD during the study period. BTAD represented 45.6% of all aortic dissections leading to hospital admission. Incidence for BTAD was 1.62 per 100 000 inhabitants per year. The median survival was 12.7 years [95% confidence interval (CI) 9.63-14.7], 12.4 years (95% CI 10.5-14.4) and 8.6 years (95% CI 7.5-9.7) for patients treated with thoracic endovascular aortic repair (TEVAR), surgery and medical treatment (MT), respectively. Survival was significantly better after TEVAR and surgery, compared to MT only (P < 0.001). Age-adjusted survival was significantly better after TEVAR compared to patients treated with MT or surgery (hazard ratio 0.578, 95% CI 0.420-0.794, P < 0.001). Aortic-related death was the most common cause of death in all groups (41%). CONCLUSIONS: The incidence of BTAD seems to be similar in the Finnish population compared to other populational studies. Patients treated with TEVAR had significantly better survival compared to other patients. A high risk for late aortic-related death should be recognized in patients with BTAD.

24-hour ambulatory blood pressure and cryptogenic ischemic stroke in young adults.

BACKGROUND: In young patients, up to 40% of ischemic strokes remain cryptogenic despite modern-day diagnostic work-up. There are limited data on blood pressure (BP) behavior in these patients. Thus, we aimed to compare ambulatory blood pressure (ABP) profiles between young patients with a recent cryptogenic ischemic stroke (CIS) and stroke-free controls. PATIENTS AND METHODS: In this substudy of the international multicenter case-control study SECRETO (NCT01934725), 24-hour ambulatory blood pressure monitoring (ABPM) was performed in consecutive 18-49-year-old CIS patients and stroke-free controls. The inclusion criteria were met by 132 patients (median age, 41.9 years; 56.1% males) and 106 controls (41.9 years; 56.6% males). We assessed not only 24-hour, daytime, and nighttime ABP but also hypertension phenotypes and nocturnal dipping status. RESULTS: 24-hour and daytime ABP were higher among controls. After adjusting for relevant confounders, a non-dipping pattern of diastolic blood pressure (DBP) was associated with CIS in the entire sample (odds ratio, 3.85; 95% confidence interval, 1.20-12.42), in participants without antihypertensives (4.86; 1.07-22.02), and in participants without a patent foramen ovale (PFO) (7.37; 1.47-36.81). After excluding patients in the first tertile of the delay between the stroke and ABPM, a non-dipping pattern of DBP was not associated with CIS, but a non-dipping pattern of both systolic BP and DBP was (4.85; 1.37-17.10). In participants with a PFO and in those without hypertension by any definition, no associations between non-dipping patterns of BP and CIS emerged. CONCLUSIONS: Non-dipping patterns of BP were associated with CIS in the absence of a PFO but not in the absence of hypertension. This may reflect differing pathophysiology underlying CIS in patients with versus without a PFO. Due to limitations of the study, results regarding absolute ABP levels should be interpreted with caution.Key MessagesNocturnal non-dipping patterns of blood pressure were associated with cryptogenic ischemic stroke except in participants with a patent foramen ovale and in those without hypertension by any definition, which may indicate differing pathophysiology underlying cryptogenic ischemic stroke in patients with and without a patent foramen ovale.It might be reasonable to include ambulatory blood pressure monitoring in the diagnostic work-up for young patients with ischemic stroke to detect not only the absolute ambulatory blood pressure levels but also their blood pressure behavior.

Nondestructive Evaluation of Mechanical and Histological Properties of the Human Aorta With Near-Infrared Spectroscopy.

INTRODUCTION: Ascending aortic dilatation is a well-known risk factor for aortic rupture. Indications for aortic replacement in its dilatation concomitant to other open-heart surgery exist; however, cut-off values based solely on aortic diameter may fail to identify patients with weakened aortic tissue. We introduce near-infrared spectroscopy (NIRS) as a diagnostic tool to nondestructively evaluate the structural and compositional properties of the human ascending aorta during open-heart surgeries. During open-heart surgery, NIRS could provide information regarding tissue viability in situ and thus contribute to the decision of optimal surgical repair. MATERIALS AND METHODS: Samples were collected from patients with ascending aortic aneurysm (n = 23) undergoing elective aortic reconstruction surgery and from healthy subjects (n = 4). The samples were subjected to spectroscopic measurements, biomechanical testing, and histological analysis. The relationship between the near-infrared spectra and biomechanical and histological properties was investigated by adapting partial least squares regression. RESULTS: Moderate prediction performance was achieved with biomechanical properties (r = 0.681, normalized root-mean-square error of cross-validation = 17.9%) and histological properties (r = 0.602, normalized root-mean-square error of cross-validation = 22.2%). Especially the performance with parameters describing the aorta's ultimate strength, for example, failure strain (r = 0.658), and elasticity (phase difference, r = 0.875) were promising and could, therefore, provide quantitative information on the rupture sensitivity of the aorta. For the estimation of histological properties, the results with α-smooth muscle actin (r = 0.581), elastin density (r = 0.973), mucoid extracellular matrix accumulation(r = 0.708), and media thickness (r = 0.866) were promising. CONCLUSIONS: NIRS could be a potential technique for in situ evaluation of biomechanical and histological properties of human aorta and therefore useful in patient-specific treatment planning.

Late-onset and classic phenotypes of Fabry disease in males with the GLA-Thr410Ala mutation.

OBJECTIVE: To present phenotypic characteristics and biomarkers of a family with the rare mutation Thr410Ala of the α-galactosidase A gene (T410A/GLA) causing Fabry disease (FD). METHODS AND RESULTS: In a woman in her 60s with hypertrophic cardiomyopathy, T410A/GLA was found in screening for variants in 59 cardiomyopathy-related genes. Her son in his 40s, two granddaughters and two great grandsons carried T410A/GLA. The son had a history of hypertension and paroxysmal AF but no microalbuminuria or classic symptoms or signs of FD. Baseline α-galactosidase A enzyme (α-Gal A) activity varied from 0% to 26.5%. Cardiac MRI showed mild Fabry cardiomyopathy (FC). During 11 years of enzyme replacement therapy (ERT), FC progressed and he suffered sudden cardiac death in his 50s. The great grandsons with T410A/GLA had no active α-Gal A, high lyso-Gb3 levels and normal cardiac imaging. They suffered from neuropathic pain and gastrointestinal symptoms and were started with ERT at the age under 10. Granddaughters with T410A/GLA had α-Gal A activities of 8-18 and 10% of normal. The older granddaughter in her 30s was diagnosed with incipient FC. Plasma lyso-Gb3 analogues were elevated, markedly in the elder male with FC and moderately in the elder granddaughter. In young males with classic phenotype, plasma lyso-Gb3 analogues were only slightly elevated. CONCLUSIONS: The T410A/GLA mutation caused late-onset FD with progressive cardiomyopathy in elder male, and classic FD in young males of the same family. Varying levels of α-Gal A and lyso-Gb3 analogues reflected variable phenotype of FD in the family.

4D Flow Versus 2D Phase Contrast MRI in Populations With Bi- and Tricuspid Aortic Valves.

AIM: To compare 4D flow magnetic resonance imaging (MRI) and 2D phase contrast (PC) MRI when evaluating bicuspid (BAV) and tricuspid (TAV) aortic valves. MATERIALS AND METHODS: A total of 83 subjects (35 BAV, 48 TAV) were explored with 4D flow and 2D PC MRI. Systolic peak velocity, peak flow and regurgitation fraction were analysed at two pre-defined aortic levels (aortic root, mid-tubular). Furthermore, the two methods of 4D flow analysis (Heart and Artery) were compared. RESULTS: Correlation between the 2D PC MRI and 4D flow MRI derived parameters ranged from moderate (R=0.58) to high (R=0.90). 4D flow MRI yielded significantly higher peak velocities in the tubular aorta in both groups. Regarding the aortic root, peak velocities were significantly higher in the TAV group with 4D flow MRI, but in the BAV group 4D flow MRI yielded non-significantly lower values. Findings on peak flow differences between the two modalities followed the same pattern as the differences in peak velocities. 4D flow MRI derived regurgitation fraction values were lower in both locations in both groups. Interobserver agreement for different 4D flow MRI acquired parameters varied from poor (ICC=0.07) to excellent (ICC=1.0) in the aortic root, and it was excellent in the tubular aorta (ICC=0.8-1.0). CONCLUSION: 4D flow MRI seems to be accurate in comparison to 2D PC MRI in normal aortic valves and in BAV with mild to moderate stenosis. However, the varying interobserver reproducibility and impaired accuracy at higher flow velocities should be taken into account in clinical practice when using the 4D flow method.

Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting.

Vascular endothelial growth factor A (VEGF-A) has therapeutic cardiovascular effects, but delivery challenges have impeded clinical development. We report the first clinical study of naked mRNA encoding VEGF-A (AZD8601) injected into the human heart. EPICCURE (ClinicalTrials.gov: NCT03370887) was a randomized, double-blind study of AZD8601 in patients with left ventricular ejection fraction (LVEF) 30%-50% who were undergoing elective coronary artery bypass surgery. Thirty epicardial injections of AZD8601 (total 3 mg) or placebo in citrate-buffered saline were targeted to ischemic but viable myocardial regions mapped using quantitative [15O]-water positron emission tomography. Seven patients received AZD8601 and four received placebo and were followed for 6 months. There were no deaths or treatment-related serious adverse events and no AZD8601-associated infections, immune reactions, or arrhythmias. Exploratory outcomes indicated potential improvement in LVEF, Kansas City Cardiomyopathy Questionnaire scores, and N-terminal pro-B-type natriuretic peptide levels, but the study is limited in size, and significant efficacy conclusions are not possible from the dataset. Naked mRNA without lipid encapsulation may provide a safe delivery platform for introducing genetic material to cardiac muscle, but further studies are needed to confirm efficacy and safety in a larger patient pool.

Wall Shear Stress Predicts Media Degeneration and Biomechanical Changes in Thoracic Aorta.

Objectives: In thoracic aortic aneurysm (TAA) of the ascending aorta (AA), AA is progressively dilating due to the weakening of the aortic wall. Predicting and preventing aortic dissections and ruptures in TAA continues to be challenging, and more accurate assessment of the AA dilatation, identification of high-risk patients, and timing of repair surgery are required. We investigated whether wall shear stress (WSS) predicts pathological and biomechanical changes in the aortic wall in TAA. Methods: The study included 12 patients with bicuspid (BAV) and 20 patients with the tricuspid aortic valve (TAV). 4D flow magnetic resonance imaging (MRI) was performed a day before aortic replacement surgery. Biomechanical and histological parameters, including assessing of wall strength, media degeneration, elastin, and cell content were analyzed from the resected AA samples. Results: WSSs were greater in the outer curves of the AA compared to the inner curves in all TAA patients. WSSs correlated with media degeneration of the aortic wall (ρ = -0.48, p < 0.01), elastin content (ρ = 0.47, p < 0.01), and aortic wall strength (ρ = -0.49, p = 0.029). Subsequently, the media of the outer curves was thinner, more rigid, and tolerated lower failure strains. Failure values were shown to correlate with smooth muscle cell (SMC) density (ρ = -0.45, p < 0.02), and indicated the more MYH10+ SMCs the lower the strength of the aortic wall structure. More macrophages were detected in patients with severe media degeneration and the areas with lower WSSs. Conclusion: The findings indicate that MRI-derived WSS predicts pathological and biomechanical changes in the aortic wall in patients with TAA and could be used for identification of high-risk patients.

Cardiac remodelling in association with left ventricular dyssynchrony and systolic dysfunction in patients with coronary artery disease.

BACKGROUND: In patients with coronary artery disease (CAD), ischaemic cardiomyopathy may result in progressive cardiac remodelling and left ventricular (LV) dysfunction. Myocardial perfusion imaging (MPI) can be used to quantify LV size and shape, mechanical dyssynchrony (LVMD) and ejection fraction (EF) as well as myocardial ischaemia and injury extents. We investigated the prevalence of LV remodelling (LVR) in patients with CAD and the relationship between LVR, LVMD and EF. METHODS: Three hundred twenty-six patients with CAD were evaluated. The EF and end-diastolic volume (EDV) were measured using MPI. LVMD was assessed using phase analysis. LVR was characterised according to LV dilatation or increased shape indices (systolic shape index [SIES] and diastolic shape index [SIED]). RESULTS: LVR were observed in 41% of CAD patients. EDV, SIES and SIED were larger in patients with LVMD or low EF. After adjustment for age, sex and infarct and ischaemia extents, phase histogram bandwidth correlated with EDV (r = 0.218) and SIES (r = 0.266) and EF correlated with EDV (r = -0.535), SIES (r = -0.554) and SIED (r = -0.217, p < 0.001 for all). CONCLUSIONS: LVR is frequently seen in patients with CAD and may be detected even before the development of symptomatic heart failure. A large LV volume and a more spherical-shaped LV were associated with LVMD and low EF, highlighting the close relationships between remodelling and systolic dyssynchrony and dysfunction. MPI is useful for assessing LVR by providing information about LV size and shape, which changes from an ellipsoid towards a spherical form in the development of ischaemic cardiomyopathy.

Safety and efficacy of the 5-lipoxygenase-activating protein inhibitor AZD5718 in patients with recent myocardial infarction: The phase 2a FLAVOUR study.

BACKGROUND: Leukotrienes are pro-inflammatory vasoactive lipid mediators implicated in the pathophysiology of atherosclerotic cardiovascular disease. We studied the effect of the 5-lipoxygenase-activating protein inhibitor AZD5718 on leukotriene biosynthesis and coronary microvascular function in a single-blind, phase 2a study. METHODS: Patients 7-28 days after myocardial infarction (±ST elevation), with <50% left anterior descending coronary artery stenosis and Thrombolysis in Myocardial Infarction flow grade ≥ 2 after percutaneous coronary intervention, were randomized 2:1:2 to once-daily AZD5718 200 mg or 50 mg, or placebo, in 4- and 12-week cohorts. Change in urine leukotriene E4 (uLTE4) was the primary endpoint, and coronary flow velocity reserve (CFVR; via echocardiography) was the key secondary endpoint. RESULTS: Of 129 randomized patients, 128 received treatment (200 mg, n = 52; 50 mg, n = 25; placebo, n = 51). Statistically significant reductions in uLTE4 levels of >80% were observed in both AZD5718 groups versus the placebo group at 4 and 12 weeks. No significant changes in CFVR were observed for AZD5718 versus placebo. Adverse events (AEs) occurred in 12/18, 3/6 and 6/13 patients receiving 200 mg, 50 mg and placebo, respectively, in the 4-week cohort, and in 27/34, 14/19 and 24/38 patients, respectively, in the 12-week cohort. Serious AEs in seven patients receiving AZD5718 and four receiving placebo were not treatment-related, and there were no deaths. CONCLUSIONS: In patients with recent myocardial infarction, AZD5718 was well tolerated, and leukotriene biosynthesis was dose-dependently inhibited. No significant changes in CFVR were detected. CLINICALTRIALS: gov identifier: NCT03317002.

Reversible myocardial ischaemia caused by ectopic left circumflex coronary artery: a case report.

Background: Coronary artery anomalies (CAAs) are congenital disorders associated with variable manifestations and pathophysiological mechanisms. Anomalies can be asymptomatic or cause chest pain, myocardial infarction, or even sudden cardiac death. Case summary: We describe a 34-year-old man with a history of a single episode of chest pain. An ectopic origin on the part of the left circumflex (LCX) coronary artery from the proximal right coronary artery (RCA) was evident upon coronary computed tomography angiography. A positron emission tomography perfusion study revealed a stress-induced perfusion defect in the anomalous LCX territory (infero-posterior wall). The patient experienced dyspnoea and ST-segment depression in electrocardiography, suggestive of myocardial ischaemia during the maximal bicycle ergometer stress test. No mechanical compression or stenosis was seen upon invasive coronary angiography. The left ventricular perfusion normalized after the initiation of beta-blocker medication. Discussion: Patients with CAAs especially benefit from a multimodality assessment of the vascular territories. In our case, the myocardial perfusion of the infero-posterior wall normalized after treatment with beta-blockers. This may be due to increased coronary vasodilation capacity and myocardial flow reserve, as well as reduced oxygen consumption. Beta-blockers may represent a viable option in low-symptomatic CAA patients with perfusion defect and no ostial stenosis or compression.

Large Vessel Cell Heterogeneity and Plasticity: Focus in Aortic Aneurysms.

Smooth muscle cells and endothelial cells have a remarkable level of plasticity in vascular pathologies. In thoracic and abdominal aortic aneurysms, smooth muscle cells have been suggested to undergo phenotypic switching and to contribute to degradation of the aortic wall structure in response to, for example, inflammatory mediators, dysregulation of growth factor signaling or oxidative stress. Recently, endothelial-to-mesenchymal transition, and a clonal expansion of degradative smooth muscle cells and immune cells, as well as mesenchymal stem-like cells have been suggested to contribute to the progression of aortic aneurysms. What are the factors driving the aortic cell phenotype changes and how vascular flow, known to affect aortic wall structure and to be altered in aortic aneurysms, could affect aortic cell remodeling? In this review, we summarize the current literature on aortic cell heterogeneity and phenotypic switching in relation to changes in vascular flow and aortic wall structure in aortic aneurysms in clinical samples with special focus on smooth muscle and endothelial cells. The differences between thoracic and abdominal aortic aneurysms are discussed.

Dilatation of the ascending aorta - Growth rate, risk factors and clinical outcomes in the long-term follow-up.

OBJECTIVES: To explore the risk factors, growth rate and outcomes of ascending aortic (AA) dilatation in patients scheduled for imaging follow-up. METHODS: This retrospective study included 143 patients who were followed-up with thoracic aortic CT-angiography. AA diameters were measured from aortic root (sinus Valsalva) and mid-AA at the baseline and after long-term follow-up. Risk factors and clinical outcomes were collected from medical records. The standard error of measurement (SEM) method was used to assess the statistical significance of the growth rate of AA dilatation. RESULTS: The patients' mean age was 64.0 ± 10.0 years (males n = 115, 80.4%). The mean imaging follow-up time was 3.4 ± 1.6 years and 5.7 ± 1.7 years in the clinical follow-up. According to the SEM method, 37.8% of the patients (n = 54) experienced significant AA growth; 18.9% (n = 27) in the aortic root (0.5 ± 0.7 mm/year), and 24.5% (n = 35) in the mid-AA (0.4 ± 0.5 mm/year). None of the patients experienced aortic rupture or dissection or died due to aortic reasons during the follow-up. Eighteen patients (12.6%) underwent elective surgical AA reconstruction and 10 patients (7.0%) died due to some other reason. Male gender was the only factor to associate with significant accelerated growth (p = 0.047). However, antihypertensive medication did seem to be a protective factor (p = 0.01). CONCLUSIONS: Less than half of the patients followed due to AA dilatation displayed significant AA growth during the long-term follow-up. In addition, the growth rate per year was small. None of the patients experienced any aortic catastrophes indicating that the prognosis of patients participating in regular imaging follow-up is good.

Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVES: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. MATERIALS AND METHODS: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. RESULTS: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. CONCLUSIONS: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.

Excess of visceral adipose tissue with or without aortic elongation leads to a steeper heart position.

BACKGROUND: The heart's position determined as the heart-aorta angle (HAA) has been demonstrated to associate with ascending aortic (AA) dilatation. Visceral adipose tissue (VAT) and aortic elongation may shift the heart to the steeper position. PURPOSE: To investigate whether VAT and aortic length influence the HAA. MATERIAL AND METHODS: We examined 346 consecutive patients (58.4% men; mean age = 67.0 ± 14.1 years) who underwent aortic computed tomography angiography (CTA). HAA was measured as the angle between the long axis of the heart and AA midline. The amount of VAT was measured at the level of middle L4 vertebra from a single axial CT slice. Aortic length was measured by combining four anatomical segments in different CTA images. The amount of VAT and aortic length were determined as mild with values in the lowest quartile and as excessive with values in the other three quartiles. RESULTS: A total of 191 patients (55.2%) had no history of aortic diseases, 134 (38.7%) displayed AA dilatation, 8 (2.3%) had abdominal aortic aneurysm (AAA), and 13 (3.8%) had both AA dilatation and AAA. There was a strong nonlinear regression between smaller HAA and VAT/height, and HAA and aortic length/height. Median HAA was 124.2° (interquartile range 119.0°-130.8°) in patients with a mild amount of VAT versus 120.5° (interquartile range 115.4°-124.7°) in patients with excessive VAT (P < 0.001). CONCLUSION: An excessive amount of VAT and aortic elongation led to a steeper heart position. These aspects may possess clinical value when evaluating aortic diseases in obese patients.

Flow displacement and decreased wall shear stress might be associated with the growth rate of an ascending aortic dilatation.

OBJECTIVES: Our goal was to evaluate whether four-dimensional (4D) flow magnetic resonance imaging (MRI) can predict the growth rate of dilatation of the ascending aorta (AA) in patients with a tricuspid, normally functioning aortic valve. METHODS: In this prospective clinical study, aortic 4D flow MRI was performed at the Kuopio University Hospital on 30 patients diagnosed with AA dilatation (maximum diameter >40 mm) between August 2017 and July 2020. The MRI was repeated after a 1-year follow-up, with AA dimensions and 4D flow parameters analysed retrospectively at both time points. The standard error of measurement was used to assess the statistical significance of the growth rate of AA dilatation. Flow displacement (FD) was transformed to a class-scaled parameter using FD ≥5% as a threshold. RESULTS: Statistically significant growth [median 2.1 mm (1.5-2.2 mm); P = 0.03] was detected in 6 male patients (20%); the AA diameter remained unchanged [0.2 mm (-0.3 to 0.9 mm)] in 24 patients (80%). An increased FD at the baseline was associated with significant growth during the 1-year follow-up in the proximal AA. An association was detected between decreased total wall shear stress and significant aortic growth in the inner curve of the sinotubular junction [529 mPa (449-664 mPa) vs 775 mPa (609-944 mPa); P = 0.03] and the anterior side of the proximal aortic arch [356 mPa (305-367 mPa) vs 493 mPa (390-586 mPa); P < 0.001]. CONCLUSIONS: FD and decreased wall shear stress seem to be associated with significant growth of AA dilatation at the 1-year follow-up. Thus, 4D flow MRI might be useful in assessing risk for AA diameter growth in patients with a tricuspid aortic valve.

Artificial Intelligence for Hospital Health Care: Application Cases and Answers to Challenges in European Hospitals.

The development and implementation of artificial intelligence (AI) applications in health care contexts is a concurrent research and management question. Especially for hospitals, the expectations regarding improved efficiency and effectiveness by the introduction of novel AI applications are huge. However, experiences with real-life AI use cases are still scarce. As a first step towards structuring and comparing such experiences, this paper is presenting a comparative approach from nine European hospitals and eleven different use cases with possible application areas and benefits of hospital AI technologies. This is structured as a current review and opinion article from a diverse range of researchers and health care professionals. This contributes to important improvement options also for pandemic crises challenges, e.g., the current COVID-19 situation. The expected advantages as well as challenges regarding data protection, privacy, or human acceptance are reported. Altogether, the diversity of application cases is a core characteristic of AI applications in hospitals, and this requires a specific approach for successful implementation in the health care sector. This can include specialized solutions for hospitals regarding human-computer interaction, data management, and communication in AI implementation projects.