Incidence and predictors of continued ascending aortic dilatation after TAVI in patients with bicuspid aortic stenosis.

BACKGROUND: Patients undergoing transcatheter aortic valve implantation (TAVI) for bicuspid aortic stenosis (AS) frequently present with ascending aortic (AAo) dilatation which is left untreated. The objective of this study was to study the natural progression and underlying mechanisms of AAo dilatation after TAVI for bicuspid AS. METHODS: Patients with a native bicuspid AS and a baseline AAo maximum diameter > 40 mm treated by TAVI and in whom post-TAVI computed tomography (CT) scans beyond 1 year were available were included. AAo dilatation was deemed to be either continuous (≥ 2 mm increase) or stable (< 2 mm increase or decrease). Uni- and multivariate logistic regression analysis was utilized in order to identify factors associated with continuous AAo dilatation post-TAVI. RESULTS: A total of 61 patients with a mean AAo maximum diameter of 45.6 ± 3.9 mm at baseline were evaluated. At a median follow-up of 2.9 years, AAo dimensions remained stable in 85% of patients. Continuous AAo dilatation was observed in 15% of patients at a rate of 1.4 mm/year. Factors associated with continuous AAo dilatation were raphe length/annulus mean diameter ratio (OR 4.09, 95% CI [1.40-16.7], p = 0.022), TAV eccentricity at the leaflet outflow level (OR 2.11, 95%CI [1.12-4.53], p = 0.031) and maximum transprosthetic gradient (OR 1.30, 95%CI [0.99-1.73], p = 0.058). CONCLUSIONS: Ascending aortic dilatation in patients undergoing TAVI for bicuspid AS remains stable in the majority of patients. Factors influencing TAV stent frame geometry and function were identified to be associated with continuous AAo dilatation after TAVI; this should be confirmed in future larger cohort studies.

Tortuosity of the left anterior descending artery is associated with hypertension and is not independently related to physical performance: A cardiac computed tomography study.

BACKGROUND: Coronary tortuosity (CorT) is frequently observed in invasive angiography, though its aetiology and clinical significance remain ambiguous. Prior research has indicated possible links between CorT and factors such as hypertension, age, and calcium scores in the left anterior descending (LAD) artery. The aim of this study was to examine and optimize the usage of coronary computed tomography angiography (CCTA) with vessel tracking to explore these associations. METHODS: Observational sub-study of the single centre randomised controlled CATCH-trial. From the original study 600 participants, who underwent CCTA, 250 were randomly selected. Clinical data and patient risk factors were sourced from medical records and structured interviews. Tortuosity of the LAD was quantified by calculating the ratio of the actual vessel-length to the straight-line distance. RESULTS: The final study population comprised 194 patients (56 patients were excluded due to poor image quality or inability to perform adequate vessel tracking). After adjusting for confounding variables, tortuosity was significantly associated with hypertension (p < 0.001), female gender (p = 0.01), and increasing age (p = 0.045). No significant correlation was observed between CorT and calcium scores. Univariate analysis indicated that higher CorT levels were linked to lower metabolic equivalents of task (METs) in bicycle tests (p = 0.003); however, this relationship became nonsignificant (p = 0.97) upon adjustment for age, gender, and hypertension. CONCLUSIONS: Our findings suggest that increased CorT is most prevalent in patients with hypertension, advancing age, and female gender. Although higher tortuosity levels did not significantly impact METs during physical activity, further research is warranted to explore the underlying mechanisms of this relationship.

Aortic aneurysms in a general population cohort: prevalence and risk factors in men and women.

AIMS: The prevalence and difference in risk factors for having thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) in men compared with women in the general population is not well described. This study aimed to test the hypotheses that (i) cardiovascular risk factors for TAA and AAA differ and (ii) the prevalence of TAA and AAA is sex specific. METHODS AND RESULTS: Aortic examination using computed tomography angiography was performed in 11 294 individuals (56% women), with a mean age of 62 (range 40-95) years participating in the Copenhagen General Population Study. TAAs were defined as an ascending aortic diameter ≥45 mm and a descending aortic diameter ≥35 mm, while AAAs were defined as an abdominal aortic diameter ≥30 mm. Demographic data were obtained from questionnaires. Overall prevalence of aortic aneurysms (AAs) in the study population included: total population 2.1%, men 4.0% and women 0.7% (P-value men vs. women P < 0.001). AAs were independently associated with male sex, increasing age, and body surface area (BSA). While TAAs were associated with hypertension, odds ratio (OR) = 2.0 [95% confidence interval (CI): 1.5-2.8], AAAs were associated with hypercholesterolaemia and smoking, OR = 2.4 (95% CI: 1.6-3.6) and 3.2 (95% CI: 1.9-5.4). CONCLUSION: Subclinical AAs are four times more prevalent in men than in women. In both sexes, increasing age and BSA are risk factors for AAs of any anatomical location. Whereas arterial hypertension is a risk factor for TAAs, hypercholesterolaemia and smoking are risk factors for AAAs.

First-In-Man Trial of ß3-Adrenoceptor Agonist Treatment in Chronic Heart Failure: Impact on Diastolic Function.

ABSTRACT: Diastolic dysfunction (DD) in heart failure is associated with increased myocardial cytosolic calcium and calcium-efflux through the sodium-calcium exchanger depends on the sodium gradient. Beta-3-adrenoceptor (ß3-AR) agonists lower cytosolic sodium and have reversed organ congestion. Accordingly, ß3-AR agonists might improve diastolic function, which we aimed to assess. In a first-in-man, randomized, double-blinded trial, we assigned 70 patients with HF with reduced ejection fraction, New York Heart Association II-III, and left ventricular ejection fraction <40% to receive the ß3-AR agonist mirabegron (300 mg/day) or placebo for 6 months, in addition to recommended heart failure therapy. We performed echocardiography and cardiac computed tomography and measured N-terminal probrain natriuretic peptide at baseline and follow-up. DD was graded per multiple renowned algorithms. Baseline and follow-up data were available in 57 patients (59 ± 11 years, 88% male, 49% ischemic heart disease). No clinically significant changes in diastolic measurements were found within or between the groups by echocardiography (E/e' placebo: 13 ± 7 to 13 ± 5, P = 0.21 vs. mirabegron: 12 ± 6 to 13 ± 8, P = 0.74, between-group follow-up difference 0.2 [95% CI, -3 to 4], P = 0.89) or cardiac computed tomography (left atrial volume index: between-group follow-up difference 9 mL/m 2 [95% CI, -3 to 19], P = 0.15). DD gradings did not change within or between the groups following 2 algorithms ( P = 0.72, P = 0.75). N-terminal probrain natriuretic peptide remained unchanged in both the groups ( P = 0.74, P = 0.64). In patients with HF with reduced ejection fraction, no changes were identified in diastolic measurements, gradings or biomarker after ß3-AR stimulation compared with placebo. The findings add to the previous literature questioning the role of impaired Na + -Ca 2+ -mediated calcium export as a major culprit in DD. NCT01876433.

Protocol for the combined cardiometabolic deep phenotyping and registry-based 20-year follow-up study of the Inter99 cohort.

INTRODUCTION: The population-based Inter99 cohort has contributed extensively to our understanding of effects of a systematic screening and lifestyle intervention, as well as the multifactorial aetiology of type 2 diabetes (T2D) and cardiovascular disease. To understand causes, trajectories and patterns of early and overt cardiometabolic disease manifestations, we will perform a combined clinical deep phenotyping and registry follow-up study of the now 50-80 years old Inter99 participants. METHODS AND ANALYSIS: The Inter99 cohort comprises individuals aged 30-60 years, who lived in a representative geographical area of greater Copenhagen, Denmark, in 1999. Age-stratified and sex-stratified random subgroups were invited to participate in either a lifestyle intervention (N=13 016) or questionnaires (N=5264), while the rest served as a reference population (N=43 021). Of the 13 016 individuals assigned to the lifestyle intervention group, 6784 (52%) accepted participation in a baseline health examination in 1999, including screening for cardiovascular risk factors and prediabetic conditions. In total, 6004 eligible participants, who participated in the baseline examination, will be invited to participate in the deep phenotyping 20-year follow-up clinical examination including measurements of anthropometry, blood pressure, arterial stiffness, cardiometabolic biomarkers, coronary artery calcification, heart rate variability, heart rhythm, liver stiffness, fundus characteristics, muscle strength and mass, as well as health and lifestyle questionnaires. In a subsample, 10-day monitoring of diet, physical activity and continuous glucose measurements will be performed. Fasting blood, urine and faecal samples to be stored in a biobank. The established database will form the basis of multiple analyses. A main purpose is to investigate whether low birth weight independent of genetics, lifestyle and glucose tolerance predicts later common T2D cardiometabolic comorbidities. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethics Committee, Capital Region, Denmark (H-20076231) and by the Danish Data Protection Agency through the Capital Region of Denmark's registration system (P-2020-1074). Informed consent will be obtained before examinations. Findings will be disseminated in peer-reviewed journals, at conferences and via presentations to stakeholders, including patients and public health policymakers. TRIAL REGISTRATION NUMBER: NCT05166447.

Gut Microbiota Alterations and Circulating Imidazole Propionate Levels Are Associated With Obstructive Coronary Artery Disease in People With HIV.

BACKGROUND: The impact of gut microbiota and its metabolites on coronary artery disease (CAD) in people with human immunodeficiency virus (PWH) is unknown. Emerging evidence suggests that imidazole propionate (ImP), a microbial metabolite, is linked with cardiometabolic diseases. METHODS: Fecal samples from participants of the Copenhagen Comorbidity in HIV infection (COCOMO) study were processed for 16S rRNA sequencing and ImP measured with liquid chromatography-tandem mass spectrometry. CAD severity was investigated by coronary computed tomography-angiography, and participants grouped according to obstructive CAD (n = 60), nonobstructive CAD (n = 80), or no CAD (n = 114). RESULTS: Participants with obstructive CAD had a gut microbiota with lower diversity and distinct compositional shift, with increased abundance of Rumiococcus gnavus and Veillonella, known producers of ImP. ImP plasma levels were associated with this dysbiosis, and significantly elevated in participants with obstructive CAD. However, gut dysbiosis but not plasma ImP was independently associated with obstructive CAD after adjustment for traditional and HIV-related risk factors (adjusted odds ratio, 2.7; 95% confidence interval, 1.1-7.2; P = .048). CONCLUSIONS: PWH with obstructive CAD displays a distinct gut microbiota profile and increased circulating ImP plasma levels. Future studies should determine whether gut dysbiosis and related metabolites such as ImP are predictive of incident cardiovascular events.

An In Silico Model for Predicting the Efficacy of Edge-to-Edge Repair for Mitral Regurgitation.

In recent years, transcatheter edge-to-edge repair (TEER) has been widely adopted as an effective treatment for mitral regurgitation (MR). The aim of this study is to develop a personalized in silico model to predict the effect of edge-to-edge repair in advance to the procedure for each individual patient. For this purpose, we propose a combination of a valve deformation model for computing the mitral valve (MV) orifice area (MVOA) and a lumped parameter model for the hemodynamics, specifically mitral regurgitation volume (RVol). Although we cannot obtain detailed information on the three-dimensional flow field near the mitral valve, we can rapidly simulate the important medical parameters for the clinical decision support. In the present method, we construct the patient-specific pre-operative models by using the parameter optimization and then simulate the postoperative state by applying the additional clipping condition. The computed preclip MVOAs show good agreement with the clinical measurements, and the correlation coefficient takes 0.998. In addition, the MR grade in terms of RVol also has good correlation with the grade by ground truth MVOA. Finally, we try to investigate the applicability for the predicting the postclip state. The simulated valve shapes clearly show the well-known double orifice and the improvement of the MVOA, compared with the preclip state. Similarly, we confirmed the improved reverse flow and MR grade in terms of RVol. A total computational time is approximately 8 h by using general-purpose PC. These results obviously indicate that the present in silico model has good capability for the assessment of edge-to-edge repair.

CNN-based fully automatic mitral valve extraction using CT images and existence probability maps.

Objective. Accurate extraction of mitral valve shape from clinical tomographic images acquired in patients has proven useful for planning surgical and interventional mitral valve treatments. However, manual extraction of the mitral valve shape is laborious, and the existing automatic extraction methods have not been sufficiently accurate. In this paper, we propose a fully automated method of extracting mitral valve shape from computed tomography (CT) images for the all phases of the cardiac cycle.Approach. This method extracts the mitral valve shape based on DenseNet using both the original CT image and the existence probability maps of the mitral valve area inferred by U-Net as input. A total of 1585 CT images from 204 patients with various cardiac diseases including mitral regurgitation were collected and manually annotated for mitral valve region. The proposed method was trained and evaluated by 10-fold cross validation using the collected data and was compared with the method without the existence probability maps.Main results. The mean error of shape extraction error in the proposed method is 0.88 mm, which is an improvement of 0.32 mm compared with the method without the existence probability maps.Significance. We present a novel fully automatic mitral valve extraction method from input to output for all phases of 4D CT images. We suggest that the accuracy of mitral valve shape extraction is improved by using existence probability maps.

The Interplay between Adipose Tissue Properties and Levels of NT-proBNP in People with HIV.

Objective: We aimed to assess the association between low N-terminal pro-brain natriuretic peptide (NT-proBNP) and body mass index (BMI), adipose tissue distribution, adiponectin, and HIV-specific risk factors among people with HIV (PWH). Methods: We included 811 PWH with measurement of height, weight and waist circumference, blood samples analyzed for NT-proBNP, and visceral-(VAT) and subcutaneous (SAT) adipose tissue areas measured from CT-scans. Low concentrations of NT-proBNP were defined as concentrations below the limit of quantification (5.9 pmol/L). Associations were explored with multivariable logistic regression analyses adjusted for relevant confounders. Results: We identified 471 (58%) individuals with low concentrations of NT-proBNP. Increasing BMI was associated with higher odds of low NT-proBNP (adjusted OR (aOR) 1.06 (95% CI: 1.01-1.11) per 1 kg/m2). Central obesity and large areas of VAT were associated with higher odds of low NT-proBNP (aOR 1.66 (1.16-2.36) and aOR 1.69 (1.09-2.62), respectively). Higher adiponectin was associated with lower odds of low NT-proBNP (aOR 0.86 (0.79-0.95) per 10% increase). No associations were found between low NT-proBNP and HIV-specific risk factors. Conclusions: In PWH, low NT-proBNP is associated with an adverse adipose tissue profile with high BMI, central obesity, accumulation of VAT, and low adiponectin.