Aims:The aim of this study was to determine the impact of obstructive coronary artery disease (CAD) and diffuse atherosclerosis on left ventricular systolic function, measured as global longitudinal strain (GLS) by cardiac magnetic resonance (CMR) feature tracking, in patients with severe aortic stenosis (AS). Methods and results:In this single-centre prospective cohort study, patients with severe AS and transcatheter aortic valve implantation (TAVI) between October 2018 and February 2022 were referred for transthoracic echocardiography, CMR, and TAVI computed tomography. Invasive coronary angiography was performed before TAVI. Ninety-four patients (80 ± 7 years) were included. The prevalence of obstructive CAD was 20 (21%) patients. The mean GLS in patients with severe AS was -24.0 ± 6.1%, and the median coronary calcium score was 802 (interquartile range 302-2130). GLS was not reduced in patients with obstructive CAD compared to other patients (23.7 ± 5.9% vs. 24.1 ± 6.2%, P = 0.83). A high coronary calcium score was not associated with GLS. Indexed left ventricular mass was independently related to GLS. Patients with an ischaemic scar on CMR had lower GLS (20.3 ± 5.1% vs. 24.6 ± 6.1%, P = 0.02). Conclusion:GLS correlated with left ventricular mass and the presence of ischaemic scar, suggesting that intrinsic myocardial disease, rather than concomitant CAD alone, accounts for reduced GLS in this population.

Cardiac organ damage (OD) is associated with increased risk of cardiovascular disease. However, limited knowledge exists on cardiac OD in young patients with cryptogenic ischaemic stroke (CIS). To explore prevalence and covariates of cardiac OD in patients with CIS compared to controls participating in the SECRETO study. We analysed data from 427 patients with CIS aged <50 years and 361 age- and sex-matched controls. OD was defined as presence of abnormal left ventricular (LV) geometry (LV hypertrophy or concentric remodelling) or left atrial enlargement (LAE) assessed by echocardiography, using sex-specific threshold values. Compared to controls, patients had higher prevalences of obesity and tobacco smoking, patent foramen ovale (PFO) (52

INTRODUCTION:This study investigates pre-atherosclerotic changes, vascular aging and clinical cardiovascular disease (CVD) risk scores in young adults with embolic stroke of undetermined source (ESUS) compared to stroke-free controls. METHODS:The study included 105 ESUS patients and 105 age- and sex-matched stroke-free controls aged 18 to 49 years. Clinical and laboratory characteristics and arterial stiffness measurements were recorded. Vascular aging indexes were defined according to age-adapted values and definitions. Clinical scores PREVENT and SCORE2 were calculated. Associations were investigated using logistic regression adjusting for several factors associated with vascular aging. RESULTS:Young ESUS patients had higher rates of central obesity, smoking, heavy alcohol consumption and patent foramen ovale compared to stroke-free controls. ESUS patients had higher odds of having excessive intima-media thickness (IMT) of the right carotid artery (OR 3.02, 95 %CI:1.31-6.92). They also had significantly higher odds of having elevated estimated pulse wave velocity (ePWV>9 m/s; OR 8.48, 95 %CI:2.16-33.4), high pulse pressure (PP ≥ 60 mmHg; OR 3.13, 95 %CI:1.28-7.68), a 10-year CVD risk above 5 % based on the PREVENT score (OR 8.53, 95 %CI:1.59-45.7), and a 10-year CVD risk above 2.5 % based on SCORE2 (OR 26.5, 95 %CI:3.6-193.6) estimated at the time of their stroke. CONCLUSIONS:Despite a low burden of established CVD, young ESUS patients harbored pathology in the vascular aging measures including IMT, ePWV, and PP. Clinical risk scores such as PREVENT and SCORE2 may effectively identify young adults at high risk of developing ESUS.

Atrial fibrillation (AF) is common in patients with aortic stenosis (AS) and complicates the assessment of AS severity. The overlapping of symptoms in these 2 conditions may postpone valve replacement. This study aimed to evaluate the effect of AF on the severity assessment of AS and its impact on symptoms and quality of life (QoL). Patients with severe AS were prospectively recruited. Echocardiography, symptom questionnaires, and RAND-36 QoL assessment were performed preoperatively and 3 months postoperatively. The aortic valve calcium score (AVC) was measured using computed tomography. Of the 279 patients, 74 (26.5%) had AF. Patients with AF had lower mean gradients and 45.9% had a low-gradient phenotype, with a mean gradient <40 mm Hg, compared with 22.4% of those without AF (p <0.001). The AVC measurements revealed severe valve calcification equally in patients with or without AF (85.7% vs 87.7%, p = 0.78). Patients with AF were more symptomatic at baseline, with 50.0% versus 27.3% in New York Heart Association class III or higher (p <0.001), and after intervention. Patients with AF had more residual dyspnea (27.3% vs 12.0%, p = 0.007) and exercise intolerance (36.4% vs 17.0%, p = 0.002). The QoL improved significantly in both groups but was worse at baseline in patients with AF and remained impaired after intervention. In conclusion, low-gradient AS phenotype is overrepresented in patients with AF, but they have equally severe stenosis determined using AVC, despite the lower gradients. Patients with AF have more symptoms and worse QoL, but they improve significantly after intervention. In patients with AF, multimodality imaging is important in the assessment of AS severity.

Introduction: Most patients with aortic stenosis (AS) are elderly and have multiple comorbidities. These conditions are often associated with poor nutrition and frailty. The purpose of this study was to assess the impact of preoperative nutritional status on symptoms and quality of life (QOL) after aortic valve replacement. Methods: We prospectively studied 220 patients with severe AS. Nutritional status was assessed using the Mini Nutritional Assessment (MNA) questionnaire. A score below 24 out of 30 indicates risk of malnutrition. Patients were evaluated preoperatively and three months after intervention. QOL was assessed using the RAND 36-item health survey. The six-minute walking test (6MWT) and the five times sit to stand test (5TSTS) were performed in 92 and 87 patients, respectively. Results: MNA score was below 24 in 28 % of the patients. Age, BMI, sex, and the proportion of patients undergoing surgery or TAVI were similar between MNA < 24 and MNA > 24 groups. There were no differences in NYHA class preoperatively, however a larger proportion of patients with MNA < 24 remained in NYHA 2 or higher after intervention (42 % vs 25 %, p = 0.03). They also remained more symptomatic, with dyspnea in 28 % vs 12 % (p = 0.01) and decreased exercise capacity in 44 % vs 16 % (p < 0.001) of the patients. Postoperative QOL was worse in patients with MNA < 24, with significant differences in seven categories (Figure). They performed worse in 6MWT at baseline (median 380 m vs 480 m, p = 0.02), but the difference was not significant after intervention (480 m vs 499 m, p = 0.4). Difference in 5TSTS was not significant at baseline (13.45 s vs 11 s, p = 0.1), but they performed worse after intervention (14.95 s vs 10.8 s, p = 0.02). Conclusions: Malnutrition is common among AS patients and is associated with worse QOL and more symptoms after intervention. Nutritional status should be assessed in AS patients before intervention for risk stratification and to find patients who might benefit from nutritional intervention.

BACKGROUND AND PURPOSE:We aimed to assess the association between covert atherosclerosis, arterial stiffness, and early-onset cryptogenic ischemic stroke (CIS) in a prospective case-control study.METHODS:We enrolled 123 young CIS patients (median age 41 years; 42% women) and 123 age- and sex-matched controls. Carotid intima-media thickness (CIMT), Augmentation Index (AIx), central pulse wave velocity (PWV), and subendocardial viability ratio (SEVR) were compared between patients and controls. Conditional logistic regression was used adjusting for age, systolic blood pressure, diastolic blood pressure, current smoking, total cholesterol/high-density lipoprotein cholesterol (Total-C/HDL-C) ratio, and glycated albumin to assess the independent association between CIMT, arterial stiffness and CIS.RESULTS:Patients with higher CIMT and PWV were older, more often men and they had more frequently well-documented risk factors, lower HDL and higher Total-C/HDL-C ratio compared to other tertiles. In univariate comparisons, we found no differences between patients and controls regarding CIMT, AIx, or PWV. In the entire cohort, patients had a significantly lower SEVR compared to controls (146.3%, interquartile range [IQR] 125.7-170.3 vs. 158.0%, IQR 141.3-181.0, P=0.010). SEVR was lower also in women compared to their controls (132.0%, IQR 119.4-156.1 vs. 158.7%, IQR 142.0-182.8, P=0.001) but no significant difference appeared between male patients and male controls. However, after adjusting for comorbidities and laboratory values these significant differences were lost (odds ratio [OR] 1.52, 95% confidence interval [CI] 0.47-4.91) in the entire cohort and OR 3.89, 95% CI 0.30-50.80 in women).CONCLUSIONS:Higher CIMT and PWV were associated to higher age, male sex, and several well-documented cardiovascular risk factors. However, in this study we could not prove that either covert atherosclerosis or arterial stiffness contribute to pathogenesis of early-onset CIS.

Abstract Funding Acknowledgements Type of funding sources: None. Background Global longitudinal strain (GLS) by echocardiography is a sensitive method for measuring left ventricular (LV) function, and of better prognostic value in valvular heart disease than ejection fraction (EF). Cardiac magnetic resonance imaging (CMR) is the most accurate method for measuring LV volume and EF, but GLS has not been possible to measure by CMR until recently. Purpose This study compares GLS obtained by CMR and echocardiography in patients with severe aortic valve stenosis. Normal values for GLS by CMR are reported as well. Methods GLS was measured in 32 patients with severe aortic valve stenosis with speckle tracking echocardiography, using GE Vivid E95 (n = 15) and Philips EPIQ (n = 17) ultrasound machines, as well as with CMR (Avanto 1.5T FIT, Siemens Medical Solutions). For normal values, GLS was measured by CMR in 9 healthy controls. Endo- and epicardial borders of two, three and four chamber cine images were traced for CMR GLS using dedicated software (Qstrain 2.0, Medis, NL). Both CMR and Vivid E95 measured midmyocardial strain, whereas the EPIQ AutoStrain method measures endomyocardial strain. Absolute values of GLS are reported. Pearson correlation coefficient was calculated and paired Student’s t-test was used for comparisons. Results A significant correlation (r = 0.45, p = 0.01) was found between echocardiographic and CMR GLS (Figure). GLS by Vivid E95 had a very good correlation with CMR GLS (r = 0.84, p = 0.0001), whereas GLS by Philips EPIQ did not correlate significantly (r = 0.14, p = 0.01). In patients with aortic stenosis and healthy controls, the average GLS by CMR was 18.3 ± 3% and 20.9 ± 2% respectively. The average GLS by CMR was comparable to that obtained by GE Vivid E95 (17.3 ± 4% vs. 17.2 ± 3%, p = 0.92), and higher than by Philips EPIQ (19.2 ± 2% vs. 15.4 ± 2%, p < 0.0001). Conclusion This study shows that GLS by CMR is feasible and correlates with GLS obtained by echocardiography, especially when quantifying midmyocardial strain. Echocardiographic GLS values based on endomyocardial strain were lower. Patient characteristics Age 75 ± 14 y NYHA 1 1 (3 %) NYHA 2 20 (67 %) NYHA 3 8 (27 %) NYHA 4 1 (3 %) CMR EF 66 ± 8 % AVA 0.7 ± 0.2 cm² NYHA = NYHA class of symptoms, EF = ejection fraction by CMR, AVA = aortic valve area by echocardiography Abstract Figure. GLS by CMR vs. Echocardiography

Epitranscriptomic modifications in RNA can dramatically alter the way our genetic code is deciphered. Cells utilize these modifications not only to maintain physiological processes, but also to respond to extracellular cues and various stressors. Most often, adenosine residues in RNA are targeted, and result in modifications including methylation and deamination. Such modified residues as N-6-methyl-adenosine (m6A) and inosine, respectively, have been associated with cardiovascular diseases, and contribute to disease pathologies. The Ischemic Heart Disease Epitranscriptomics and Biomarkers (IHD-EPITRAN) study aims to provide a more comprehensive understanding to their nature and role in cardiovascular pathology. The study hypothesis is that pathological features of IHD are mirrored in the blood epitranscriptome. The IHD-EPITRAN study focuses on m6A and A-to-I modifications of RNA. Patients are recruited from four cohorts: (I) patients with IHD and myocardial infarction undergoing urgent revascularization; (II) patients with stable IHD undergoing coronary artery bypass grafting; (III) controls without coronary obstructions undergoing valve replacement due to aortic stenosis and (IV) controls with healthy coronaries verified by computed tomography. The abundance and distribution of m6A and A-to-I modifications in blood RNA are charted by quantitative and qualitative methods. Selected other modified nucleosides as well as IHD candidate protein and metabolic biomarkers are measured for reference. The results of the IHD-EPITRAN study can be expected to enable identification of epitranscriptomic IHD biomarker candidates and potential drug targets.

Background Aortic valve stenosis (AS) is the most prevalent valvular disease in the developed countries. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) is an emerging imaging technique, which has been suggested to improve the evaluation of AS severity compared to two-dimensional (2D) flow and transthoracic echocardiography (TTE). We investigated the reliability of CMR 2D flow and 4D flow techniques in measuring aortic transvalvular peak systolic flow in patients with severe AS. Methods We prospectively recruited 90 patients referred for aortic valve replacement due to severe AS (73.3 ± 11.3 years, aortic valve area 0.7 ± 0.1 cm 2 , and 54/36 tricuspid/bicuspid), and 10 non-valvular disease controls. All the patients underwent echocardiography and 2D flow and 4D flow CMR. Peak flow velocity measurements were compared using Wilcoxon signed rank sum test and Bland–Altman analysis. Results 4D flow underestimated peak flow velocity in the AS group when compared with TTE (bias − 1.1 m/s, limits of agreement ± 1.4 m/s) and 2D flow (bias − 1.2 m/s, limits of agreement ± 1.6 m/s). The differences between values obtained by TTE (median 4.3 m/s, range 2.7–6.1 m/s) and 2D flow (median 4.5 m/s, range 2.9–6.5 m/s) compared to 4D flow (median 3.1 m/s, range 1.7–5.1 m/s) were significant (p < 0.001). The difference between 2D flow and TTE were insignificant (bias 0.07 m/s, limits of agreement ± 1.5 m/s). In non-valvular disease controls, peak flow velocity was measured higher by 4D flow than 2D flow (1.4 m/s, 1.1–1.7 m/s and 1.3 m/s, 1.1–1.5 m/s, respectively; bias 0.2 m/s, limits of agreement ± 0.16 m/s). Conclusions CMR 4D flow significantly underestimates systolic peak flow velocity in patients with severe AS. 2D flow, in turn, estimated the AS velocity accurately, with measured peak flow velocities comparable to TTE.

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Helsinki University Hospital, Finland Background Aortic stenosis (AS) is the most prevalent valvular disease in the developed countries. 4D flow is an emerging cardiac magnetic resonance (CMR) imaging technique, which has been suggested to improve the evaluation of AS severity. The accuracy of peak flow measurement by 4D flow CMR in patients with severe AS has, however, remained unvalidated. Purpose We investigated the reliability of the novel 4D flow CMR technique in measuring transvalvular peak systolic flow in patients with severe aortic valve stenosis. Methods The study included 63 patients clinically evaluated for valve replacement due to severe symptomatic AS. All the patients underwent echocardiography, 2D phase-contrast and 4D flow CMR. CMR was performed on consecutive patients according to international guidelines. Mean age of the patients was 73.8 ± 11.5 years, mean aortic valve area 0.7 ± 0.2 cm², and 40 of the valves were tricuspid and 23 bicuspid. QFlow and QFlow 4D software were used for flow analyses. Bland-Altman analyses and Wilcoxon signed rank sum tests were performed using SPSS software. Results CMR 4D flow analyses underestimated peak flow values when compared with echocardiography (bias -1.1 m/s, limits of agreement ± 1.5 m/s) and with 2D flow analyses (bias -1.2 m/s, limits of agreement ± 1.7 m/s). The difference between values obtained by 4D flow (median 3.1 m/s, range 1.5 – 4.9 m/s) and echocardiography (median 4.3 m/s, range 2.1 – 6.1 m/s) as well as by 2D flow (median 4.3 m/s, range 2.0 – 8.4 m/s) were statistically significant (p < 0,001). The difference between 2D flow analyses and echocardiography remained statistically insignificant (bias 0.05 m/s, limits of agreement ± 1.6 m/s). Conclusions We found that 4D flow analysis significantly underestimates systolic peak flow values in patients with severe AS. This may be due to intra-voxel averaging of the narrow jets. In contrast to previous assumptions, traditional 2D flow technique may therefore outperform 4D flow in measuring valvular peak flow by CMR in patients with severe AS. This should be taken into consideration when assessing disease severity by CMR. Abstract Figure. Peak systolic flow in AS patients (n = 63)