Remodeling Index Research Articles

The effect of adrenalectomy on bleomycin-induced pulmonary fibrosis in mice.

Progressive lung fibrosis is often fatal and has limited treatment options. Though the mechanisms are poorly understood, fibrosis is increasingly linked with catecholamines such as adrenaline (AD) and noradrenaline (NA), and hormones such as aldosterone (ALD). The essential functions of the adrenal glands include the production of catecholamines and numerous hormones, but the contribution of adrenal glands to lung fibrosis remains less well studied. Here, we characterized the impact of surgical adrenal ablation in the bleomycin model of lung fibrosis. Wild type mice underwent surgical adrenalectomy or sham surgery followed by bleomycin administration. We found that while bleomycin-induced collagen over-deposition in the lung was not affected by adrenalectomy, histologic indices of lung remodeling were ameliorated. These findings were accompanied by a decrease of lymphocytes in bronchoalveolar lavage (BAL) and macrophages in lung tissues, along with concomitant reductions in alpha smooth muscle actin (⍺SMA) and fibronectin. Surgical adrenalectomy completely abrogated AD, not NA, detection in all compartments. Systemic ALD levels were reduced after adrenalectomy while ALD levels in lung tissues remained unaffected. Taken together, these results support the presence of a pulmonary-adrenal axis in lung fibrosis and suggest that adrenalectomy is protective in this disease. Further investigation will be needed to better understand this observation and aid in the development of novel therapeutic strategies.

Development of Remodeling Index Prediction Model of Deteriorated Asphalt Pavements for Large-Scale Repair Works

Development of Remodeling Index Prediction Model of Deteriorated Asphalt Pavements for Large-Scale Repair Works

Early increase and subsequent decrease in mature BNP and early decrease and continued decrease in proBNP after sacubitril/valsartan may relate to left ventricular reverse remodeling in heart failure

Abstract Background Current BNP assays measure not only mature BNP (BNP1-32) but also precursor proBNP. Previous studies have shown that the change in BNP after sacubitril/valsartan (Sac/Val) treatment is not consistent. The reason for this may be due to the fact that the immunoreactivity of BNP consists of mature BNP and proBNP and neprilysin degrades only mature BNP but not proBNP. Purpose This study assessed changes in mature BNP, proBNP, total BNP (= mature BNP + proBNP) before and 2 and 12 weeks after administration of Sac/Val in heart failure (HF). Methods We measured mature BNP, proBNP, and total BNP levels by our developed immunoassay, NT-proBNP and ANP by conventional assay and left ventricular (LV) remodeling indices by echocargdioraphy in 34 HF patients before, 2, and 12 weeks (wk) after Sac/Val treatment. 34 HF patients were divided into two groups. Group D (n=20) was defined as the group whose mature BNP at 12wk was lower than the baseline. Whereas Group I (n=14) was defined as the group whose mature BNP at 12wk was higher than the baseline. Results In all patients, total BNP did not change after 2wk or 12wk compared to baseline. ProBNP decreased after 2wk and tended to decrease after 12wk (p=0.07). Whereas there was no change inmature BNP after 2wk or 12wk (Table 1). In group D, total BNP did not change at 2wk, but decreased after 12wk. Mature BNP did not change at 2wk, but decreased after 12wk. ProBNP decreased at 2wk and further decreased at 12wk. In contrast, in group I total BNP did not change at 2wk, but increased at 12wk. ProBNP did not change after 2wk or 12wk compared to baseline. Mature BNP increased after 2wk and further increased after 12wk. Thus, a decrease in both proBNP and mature BNP contributed to the decrease in total BNP in group D, while the increase in total BNP in group I was mainly due to the increase in mature BNP. Correlation coefficient and p value between total BNP, proBNP, mature BNP, NT-proBNP and ANP at baseline, 2wk and 12wk are shown in Table 2. A close correlation was observed between BNP molecular forms. NT-proBNP decreased and ANP increased after Sac/Val administration; however, there was a modest correlation between the two peptides. There were no significant differences in LV ejection fraction (LVEF: %), end-diastolic volume index (LVEDVI: ml/m²) or end-systolic volume index (LVESVI: ml/m²) between two groups at baseline or at 12 wk; however, the delta (at 12 wk – pretreatment) LVEDVI, and LVESVI significantly improved in group D compared with group I (-9.3±11.3 vs. 3.7±10.1, p<0.01; -8.2±13.5 vs. 2.7±8.9, p<0.01, respectively). Conclusion These results suggest that total BNP appears to be unchanged after Sac/Val administration, but its components, proBNP and mature BNP, are altered; reverse cardiac remodeling may relate to decrease of mature BNP and proBNP; and the closely correlated natriuretic peptide molecules, regardless of the degradation by neprilysin, may be regulated in the same direction.

Clustering of artificial intelligence derived plaque features for risk stratification for future atrial fibrillation development

Abstract Introduction We previously demonstrated that artificial intelligence (AI)-derived coronary artery plaque features are associated with future development of atrial fibrillation (AF) among patients undergoing CCTA(1). Our results suggest that phenotyping a large dataset of plaque features using data science techniques may reveal associations not visible from univariate analysis. Purpose Use data science analysis of AI-CT plaque characteristics to identify subpopulations at higher risk of AF. Methods We applied dimensionality reduction and visual cluster identification to phenotype our population of patients based on their AI-CT plaque features. We used a single center CCTA registry of patients with prior clinically-indicated CCTA (N=2700) from 2017-2020. Cases of new AF were defined by onset of AF on ECG or telemetry after CCTA via EMR search. Patients with AF prior to CCTA, history of mitral valve surgery, or postoperative AF were excluded. Controls were selected 1:1 by nearest neighbor propensity matching (R. v. 4.0.3.) based on age, sex, tobacco use, HTN, HLD, and diabetes. Atherosclerotic plaques were quantitatively analyzed using a commercially available FDA-approved AI coronary analysis software yielding stenosis area and diameter, remodeling index, volume of calcified/non-calcified/low-density plaques, and number of 2 or more high risk plaques. Uniform Manifold Approximation and Projection (UMAP) dimensionality reduction with cosine distance metric was used to reduce the plaque feature space from 80 dimensions (8 AI measurements per each of 10 anatomical vessel segments in all patients) to 2 dimensions on a scatter plot. Two non-contiguous clusters (i.e. plaque phenotypes) were identified based on visual analysis of UMAP feature reduction (Figure 1). Results 94 cases comprised the study cohort (47 cases and 47 controls). Mean age was 67±11 years. 38% were female. Mean CADRADS score was 1.8±1.52 and mean CAC was 325±622. Mean time from CT to AF was 281±300 days. The majority of AF patients (67%) fell into Cluster 1 (N=36), while Cluster 2 (N=58) contained most of the control subjects (75%). Treating Cluster 1 as a predictor of AF, the PPV and specificity of the UMAP reduction was 67% and 75% respectively, with NPV of 60% and sensitivity of 51% (Table 1). Left atrial volume index (LAVI) was significantly different between the 2 clusters, with mean 56.15±12.42 ml/m2 in Cluster 1 and 46.96±16.03 in Cluster 2 (p=0.0046). LAVI was also significantly different between control subjects in Cluster 1 vs 2, mean 54.84±11.6 vs 41.62±7.92 (p<0.001). Conclusions We demonstrated that UMAP-derived clustering of AI-CT plaque characteristics identifies novel phenotypes for future risk of AF among patients undergoing CCTA. Further, control patients in Cluster 1 were found to have a significantly higher LAVI compared to control subjects in Cluster 2, which supports that membership in Cluster 1 may increase risk of future development of AF.

Valvular and myocardial fibroblast activation in aortic stenosis: a prospective positron emission tomography study

Abstract Introduction In patients with aortic stenosis, fibrosis is a common pathophysiological feature of leaflet thickening as well as left ventricular decompensation as it transitions from hypertrophy to heart failure. Valvular fibrosis can be quantified by contrast-enhanced computed tomography, and myocardial fibrosis by late gadolinium enhancement on magnetic resonance imaging, but neither can detect the activity of fibrosis and extracellular matrix remodelling. Gallium-68 Fibroblast Activation Protein Inhibitor (68Ga-FAPI) binds to activated fibroblasts, the key effector cell of fibrogenesis, and provides a measure of fibroblast activation and fibrosis activity. We aimed to measure fibrosis activity in the aortic valve and left ventricular myocardium of patients with aortic stenosis using 68Ga-FAPI uptake. Methods In a prospective observational cohort, patients with aortic stenosis and control subjects with normal aortic valves underwent transthoracic echocardiography, 68Ga-FAPI positron emission tomography, computed tomography, and magnetic resonance imaging. Valvular and myocardial 68Ga-FAPI uptake was quantified using the target-to-background ratio (TBRmax). Valvular non-calcific volume was quantified on computed tomography and replacement myocardial fibrosis was quantified by late gadolinium enhancement on magnetic resonance imaging. Results Fifty patients with aortic valve disease (9 with aortic sclerosis, and 7 with mild, 23 with moderate and 11 with severe aortic stenosis; 72±8 years, 70% male) and 4 control subjects (66±7 years, 50% male) participated. Increased 68Ga-FAPI uptake was observed in the aortic valves of patients with aortic sclerosis and stenosis and peaked in those with moderate disease (Figure 1). TBRmax of 68Ga-FAPI uptake correlated with the aortic valve non-calcific volume (r=0.354, p<0.05) on computed tomography. Thirty-one patients (62%) had myocardial 68Ga-FAPI uptake, of whom half (n=17; 34%) also had late gadolinium enhancement corresponding to the region of 68Ga-FAPI uptake (Figure 2). Myocardial 68Ga-FAPI uptake correlated with increased indexed left ventricular mass (r=0.333, p<0.05) and left ventricular wall thickness (r=0.385, p<0.05). Conclusions For the first time, we have identified both valvular and myocardial fibrosis activity in patients with aortic stenosis. Valvular fibroblast activation is increased in patients with aortic sclerosis and stenosis, peaking in patients with moderate disease and correlating with leaflet thickening. Myocardial fibroblast activation is seen in the majority of patients with aortic stenosis both in areas with and without established fibrosis, and is associated with indices of adverse left ventricular remodelling. Activated fibroblasts are thus an important potential treatment target in the valve and myocardium, with 68Ga-FAPI positron emission tomography holding major promise in better understanding the pathophysiology, progression and consequences of aortic stenosis.

Clustering analysis based on clinically available data for improving risk stratification and outcome prediction of hypertension

Abstract Background Hypertension (HTN) is a heterogeneous condition with several factors contributing to adverse outcomes. Machine learning can harness complex data to unveil outcome predictors and guide prevention. Purpose To use clustering analysis on clinical data to identify HTN risk profiles and their associations with cardiovascular abnormalities and clinical outcomes. Methods A cohort of 14,840 UK Biobank hypertensive participants without pre-existing heart failure (HF) who underwent cardiovascular magnetic resonance (CMR) assessment was examined using K-means clustering on 79 clinical attributes. The clusters’ association with incident HF, mortality, atrial fibrillation (AF), and major adverse cardiovascular events (MACE) were evaluated, alongside imaging characteristics, with mediation analysis probing the role of imaging in risk differentiation. All post-hoc analyses were adjusted for vascular risk factors (VRFs), including diabetes, hypercholesterolaemia, previous myocardial infarction. Results Three distinct clusters differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles were identified. Cluster 1 (lowest risk), predominantly females, exhibited the most favourable metabolic profile and outcomes. Cluster 2 (highest risk), predominantly males, had the most adverse metabolic and cardiovascular profiles, and the highest risk of all adverse outcomes, especially AF and HF (hazard ratio (HR) 1.80 [1.45–2.25] and 1.85 [1.39–2.46]; p <0.005). This group was associated with more eccentric LV hypertrophy (LVH), overall poorer left atrial emptying function (LAEF), bi-ventricular systolic function and LV mechanics, and higher systemic vascular resistance (Figure 1). Cluster 3 (intermediate risk) was a more heterogeneous group with the highest burden of diabetes and adiposity and a moderate rise in AF and MACE risk (HR 1.61 [1.12-2.32] and 1.30 [1.07-1.58]; p <0.05). This cluster was associated with concentric LV remodelling and better indices of cardiac mechanics, but greater impairment in LA booster pump function (active LAEF) than Cluster 2 (Figure 1). Cluster 2's effect on MACE was mostly mediated through LV mass increase (proportion mediated, 67%), followed by changes (reducing) in LV global longitudinal strain (33%), and ejection fraction (25.4%). The indirect effect of CMR changes in the association between cluster 3 and MACE was much smaller with the highest proportion of the effects mediated through increased myocardial wall thickness (26%) but not LV mass, and changes in all the components of LA function. Conclusions Clinical data clustering provides insight into distinct HTN risk profiles, each with specific imaging characteristics and clinical trajectories, hinting at different pathophysiological mechanisms. Enhanced phenotyping can facilitate tailored interventions based on the disease subtype and improve clinical outcomes.Figure 1.

Computed tomography for prediction of stent underexpansion after percutaneous recanalization of calcified coronary chronic total occlusions

Abstract Background Coronary calcifications are the leading cause of stent underexpansion after percutaneous coronary intervention (PCI) and are commonly encountered in chronic total occlusions (CTO). Coronary computed tomography angiography (CCTA) is uniquely suited for pre-procedural assessment of coronary calcifications. Recently quantitative CCTA, providing exact volumes of each plaque component, has shown additional value in future risk assessment compared with conventional qualitative CCTA. Purpose The aim of this study was to evaluate whether CCTA predicts intravascular ultrasound (IVUS)-defined suboptimal stent expansion following percutaneous recanalization of calcified CTO lesions. Methods We retrospectively identified consecutive patients with a CCTA performed within 6-months prior to successful PCI of a calcified CTO (defined as calcification within the target lesion on CCTA). All patients had final IVUS of implanted stents (Figure 1). Patients requiring atherectomy were excluded. The primary outcome was IVUS-derived stent expansion index (SEI), defined as stent area divided by vessel area (both measured at the site of maximum calcium). SEI<0.4 indicated suboptimal stent expansion. The site of maximum calcium was a cross-section with greatest calcium arc on pre-stent IVUS within the target lesion. CCTA calcium analysis was performed by a researcher blinded to the IVUS and angiography results. Measurements included total-, vessel-, and lesion-specific calcium score (CAC), total calcium length, maximum calcium thickness and maximum CT calcium attenuation at the target lesion defined as occlusion site and adjacent severely diseased segments. Calcium quantification was performed using a semi-automated software to obtain volumes and burdens of calcified and non-calcified plaque components within the target lesion. Results The cohort included 43 patients (age 64.9±10.0 years, 88% males) with 43 CTO lesions. Mean final stent area at maximum calcium by IVUS was 8.2±2.1mm². Mean SEI was 0.47±0.1, and suboptimal SEI of <0.4 was found in 10 (23.3%) lesions. Lesions with suboptimal stent expansion (SEI<0.4) were characterized by numerically higher total-, vessel- and lesion-specific CAC, higher maximum calcium attenuation, greater calcium length and remodeling index compared with patients with optimal stent expansion (Table 1). However, only calcified plaque volume (105 [IQR 27-271] vs. 29 [4-96]mm³, P=0.02) and calcified plaque burden (16 [7-24] vs. 6 [1-10]%, P=0.03) were significantly greater in lesions with suboptimal stent expansion compared with lesions with optimal stent expansion, respectively. Calcified plaque volume ≥51 mm³ within the target lesion predicted suboptimal stent expansion with 70% sensitivity and 62.5% specificity (AUC 0.74). Conclusion CCTA-derived calcium volume identifies CTO lesions at greater risk of stent underexpansion. Such lesions require more aggressive plaque modification prior to stent implantation.

Predicting outcomes of unruptured intracranial artery dissection with clear symptoms onset using clinical and radiological features

We investigated the clinical and radiologic predictors of unruptured symptomatic intracranial artery dissection (IAD) outcomes. Unruptured symptomatic IAD patients who underwent vessel wall magnetic resonance imaging (VW-MRI) and time-of-flight magnetic resonance angiography (TOF-MRA) within 1 month after symptom onset, followed for over 12 months were included. Baseline features predicting the clinical outcome of recurrent symptoms and radiologic outcomes of aneurysmal dilatation and occlusion were analyzed using logistic regression analysis. The Kaplan–Meier method calculated the median time to morphological stability. Patients with aneurysmal dilatation were categorized into progressive and non-progressive enlargement subgroups. Seventy-three IADs from 65 patients were included. All patients showed benign clinical course (mRS 0–1). No baseline features were predictive of recurrent symptoms. Aneurysmal dilatation was associated with increased outer diameter in baseline VW-MRI (OR, 23.15; 95% CI, 3.78–141.75, P < 0.001) and TOF-MRA (OR, 10.81; 95% CI, 2.16–53.99, P = 0.004). Occlusion was inversely associated with preserved patency in baseline VW-MRI (OR, 0.1; 95% CI, 0.01–0.74, P = 0.024) and TOF-MRA (OR, 0.14; 95% CI, 0.02–0.98; P = 0.048). The median time to morphological stability was 3.9 months (95% CI, 3.16–5.5). While baseline features did not significantly differ between aneurysmal dilatation subgroups, follow-up imaging revealed significant differences in remodeling index, normalized wall index, relative signal intensity of intramural hematoma, and presence of onion-skin appearance and intramural hematoma (all P < 0.05). Our findings suggest that while unruptured IAD presents a benign clinical outcome, follow-up imaging may be necessary to monitor the progressive enlargement of aneurysmal dilatation.

Evaluation of cardiac remodeling in pediatric chronic kidney disease by cardiovascular magnetic resonance

BackgroundChildren with chronic kidney disease (CKD) are at high risk of cardiovascular disease. Cardiovascular magnetic resonance (CMR) is the reference method for assessing cardiac remodeling. To our knowledge, no study has reported a comprehensive analysis of left ventricular(LV) cardiac remodeling using CMR in different stages of pediatric CKD. This prospective case-control study aimed to investigate cardiac remodeling in pediatric CKD, using CMR, and determine its relationship with risk factors.MethodCMR was performed in 124 children with CKD and 50 controls. The cardiac remodeling parameters included left ventricular mass index (LVMI), LV remodeling index (LVRI), and LV wall thickness. Univariable and multivariable analyses were performed to assess the cardiac remodeling risk factors.ResultsCardiac remodeling was observed in 35.5% (44/124) of children with CKD. The LVMI, LVRI, and LV wall thickness were higher in advanced stages of CKD (P < 0.05). In the CKD stage 1–2 group, a lower in the estimated glomerular filtration rate was an independent determinant of impaired LVMI (β = −0.425, P = 0.019) and LVRI (β = −0.319, P = 0.044). A higher protein to creatinine ratio(PCR) was independently associated with impaired LVRI (β = 0.429, P = 0.022). In the CKD stage 3–5 group, higher in systolic blood pressure (SBP) (β = 0.464, P = 0.005) and PCR (β = 0.852, P = 0.031) were independent determinants of impaired LVMI. Additionally, higher SBP was positively correlated with impaired LVRI(r = 0.599, P < 0.001). There was a trend toward more abnormal cardiac remodeling in the CKD stage 3–5 group with hypertension than those without.ConclusionCardiac remodeling is prevalent in children with CKD, from an early stage. kidney markers are independently associated with cardiac remodeling. Hypertension increases the risk of cardiac remodeling in CKD stages 3–5. Strict BP control may help reverse or prevent remodeling.

Sensitization to Staphylococcus Enterotoxin: Relationship with Aspects of Disease Severity

Background/Objective: Sensitization to specific IgE Staphylococcus aureus enterotoxins (SEs) is associated with an increased risk for severe asthma development. Limited data exist regarding the association of seropositivity for specific IgE SEs and the different aspects of severe asthma. We aimed to determine whether the presence of SEs is associated with asthma-related parameters such as inflammatory cells in the airways, features of airway remodeling, and other variables relating to asthma assessment and severity. Methods: Fifty patients with severe asthma were recruited in the study. Demographics, comorbidities, asthma duration, and asthma medication were recorded by treating physicians. Specific IgE SE measurement, lung function, atopic status, asthma control test (ACT), sputum induction, bronchoscopy with BAL, and indices of airway remodeling were also assessed. Results: Twelve patients were positive to enterotoxin sensitization. Patients seropositive to specific IgE SEs significantly differed in regard to FEV1% pred and FEV1/FVC ratio compared to seronegative ones. Analyzing the inflammatory variables obtained from induced sputum, BAL, and endobronchial biopsies, the only significant difference was that of smooth muscle area (SMA), which was greater in specific IgE SE seropositive patients. The multivariate linear regression analysis showed two significant associations of specific IgE SE seropositivity. We found a negative with FEV1% pred with beta standardized coefficient 95%CI −0.054 (−0.083, −0.031), p &lt; 0.001, and a positive with SMA with beta standardized coefficient 95%CI 0.054 (0.081, 0.037), p &lt; 0.001. Conclusions: Seropositivity to specific IgE SEs in severe asthma is associated with more severe airflow limitation, obstruction, and upregulation in SMA, indicating a possible role in the remodeling process.

Correlation of serum homocysteine and cystatin C levels with prognosis in heart failure with preserved ejection fraction patients

ObjectiveThis study investigated the relationship of serum homocysteine (Hcy) and cystatin C (Cys C) levels with the prognosis of patients with heart failure with preserved ejection fraction (HFpEF).MethodsA total of 178 patients with HFpEF who were admitted to our hospital between December 2019 and November 2020 were included. Patients were grouped based on their serum Hcy and Cys C levels: high Hcy level, normal Hcy level, high Cys C level, and normal Cys C level. Cardiac function, ventricular remodeling indices, and prognosis were compared among patients in these groups. Additionally, the predictive value of serum Hcy and Cys C levels for adverse cardiovascular events in HFpEF patients was analyzed.ResultsPatients’ mean age in the high Hcy level, normal Hcy level, high Cys C level, and normal Cys C level groups was 69.21 ± 4.17,67.74 ± 4.28,69.95 ± 4.98, and 67.06 ± 4.13 years old, respectively. The high Hcy level group exhibited a lower proportion of class II cardiac function according to the New York Heart Association (NYHA) classification and a higher proportion of class IV cardiac function than the normal Hcy level group, with statistically significant differences. Similarly, the high Cys C level group had a lower proportion of class II cardiac function and a higher proportion of class IV cardiac function compared with the normal Cys C level group, with statistically significant differences. Left ventricular end-diastolic internal diameter (LVEDD), left ventricular end-systolic internal diameter (LVESD), and left ventricular mass index (LVMI) were significantly higher in both the high Hcy level and high Cys C level groups compared with the normal group, with statistically significant differences. The rates of all-cause mortality and class I endpoint events were significantly higher in the high Hcy level and high Cys C level groups than in the normal group. Multifactorial logistic regression analysis demonstrated that adverse cardiovascular events were significantly associated with cardiac function class, LVEDD, LVESD, LVMI, Hcy, and Cys C in patients with HFpEF. The area under the curve (AUC) values for Hcy and Cys C, determined using receiver operating characteristic (ROC) curve analysis, were 0.778 (optimal critical value, 25.38) and 0.681 (optimal critical value, 1.56), respectively, for predicting adverse cardiovascular events. Both Hcy and Cys C serum levels were positively correlated with LVEDD, LVESD, LVMI, and NYHA classification.ConclusionSerum levels of Hcy and Cys C were closely associated with cardiac function, ventricular remodeling indices, and prognosis in patients with HFpEF. These levels may serve as valuable indices for assessing HFpEF patients’ health status and prognosis, providing important insights into their potential role as biomarkers for HFpEF management and prognosis.

Mitral valve calcinosis as an important finding during heart examination

BACKGROUND: Mitral valve calcinosis is a chronic degenerative process in the fibrous structures of the mitral valve. Advanced stages increase the risk of endocarditis and cardiac rhythm disturbances and contribute to cardiovascular mortality. The cause of mitral valve calcinosis is still controversial; however, the contribution of atherosclerosis to its development is currently undisputed. The prevalence of mitral valve calcinosis varies in different age groups and on average is higher in people with cardiovascular disease. AIM: To assess the prevalence of mitral valve calcinosis in patients undergoing computed tomography angiography and identify the relationship between aortic and mitral valve calcinosis and coronary calcium index and signs of remodeling. MATERIALS AND METHODS: A retrospective study of 336 patients who underwent computed tomography coronary angiography with intravenous contrast enhancement at the Lomonosov Moscow State University Clinic between November 13, 2020, and May 14, 2022, was conducted. RESULTS: The prevalence of aortic (16.4%) and mitral (11%) valve calcinosis was high in people undergoing cardiovascular examination, and a relationship was noted between valve calcinosis and coronary calcium index. CONCLUSION: The detection of mitral valve calcinosis in patients during routine examination is important in predicting further treatment and outcomes because valve calcinosis is an indirect indicator of coronary heart disease risk. Although valve calcinosis is usually an incidental examination finding, it may indicate a high cardiovascular risk and should prompt further evaluation, if clinically necessary.

The differential effects of dyslipidemia status and triglyceride-glucose index on left ventricular global function and myocardial microcirculation in diabetic individuals: a cardiac magnetic resonance study

BackgroundIt remains unclear whether the association between dyslipidemia status and triglyceride-glucose (TyG) index with myocardial damage varies in the context of type 2 diabetes mellitus (T2DM). This study aimed to determine the differential effects of dyslipidemia status and TyG index on left ventricular (LV) global function and myocardial microcirculation in patients with T2DM using cardiac magnetic resonance (CMR) imaging.MethodsA total of 226 T2DM patients and 72 controls who underwent CMR examination were included. The T2DM group was further categorized into subgroups based on the presence or absence of dyslipidemia (referred to as T2DM (DysL+) and T2DM (DysL-)) or whether the TyG index exceeded 9.06. CMR-derived LV perfusion parameters, remodeling index, and global function index (GFI) were assessed and compared among groups. A multivariable linear regression model was employed to evaluate the effects of various variables on LV myocardial microcirculation, remodeling index, and GFI.ResultsThe LV GFI sequentially decreased in controls, T2DM (DysL-), and T2DM (DysL+) groups (p < 0.001), and was lower (p = 0.003) in T2DM with higher TyG index group than in lower TyG index group. The LV remodeling index was higher in higher TyG index group than in lower TyG index group (p = 0.002), but there was no significant difference in whether the subgroup was accompanied by dyslipidemia. Multivariable analysis revealed that the TyG index, but not dyslipidemia status, was independently associated with LV remodeling index (β coefficient[95% confidence interval], 0.152[0.025, 0.268], p = 0.007) and LV GFI (− 0.159[− 0.281, − 0.032], p = 0.014). For LV myocardial microcirculation, perfusion index, upslope, and max signal intensity sequentially decreased in controls, T2DM (DysL-), and T2DM (DysL+) groups (all p < 0.001). Dyslipidemia status independently correlated with perfusion index (− 0.147[− 0.272, − 0.024], p = 0.02) and upslope (− 0.200[− 0.320, 0.083], p = 0.001), while TyG index was independently correlated with time to maximum signal intensity (0.141[0.019, 0.257], p = 0.023).ConclusionsBoth dyslipidemia status and higher TyG index were associated with further deterioration of LV global function and myocardial microvascular function in the context of T2DM. The effects of dyslipidemia and a higher TyG index appear to be differential, which indicates that not only the amount of blood lipids and glucose but also the quality of blood lipids are therapeutic targets for preventing further myocardial damage.

B-flow/spatiotemporal image correlation M-mode ultrasound provides novel method to quantify spiral artery remodeling during normal human pregnancy.

During human pregnancy, placental extravillous trophoblasts replace vascular smooth muscle and elastic tissue within the walls of the uterine spiral arteries, thereby remodeling them into distensible low-resistance vessels to promote placental perfusion. The present study determined whether B-flow/spatiotemporal image correlation (STIC) M-mode ultrasonography provides an in-vivo imaging method able to digitally quantify spiral artery luminal distensibility as a physiological index of spiral artery remodeling during the advancing stages of normal human pregnancy. A prospective, longitudinal, observational study was conducted to quantify spiral artery distensibility (i.e. vessel luminal diameter at systole minus diameter at diastole) by B-flow/STIC M-mode ultrasonography during the first, second and third trimesters in 290 women exhibiting a normal pregnancy. Maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1), growth factors that modulate important events in spiral artery remodeling, were quantified in a subset of the women in the first, second and third trimesters of pregnancy. Median (interquartile range (IQR)) spiral artery distensibility increased progressively between the first (0.17 (0.14-0.21) cm), second (0.23 (0.18-0.28) cm) and third (0.26 (0.21-0.35) cm) trimesters of pregnancy (P < 0.0001 for all). Median (IQR) spiral artery volume flow increased progressively between the first (2.49 (1.38-4.99) mL/cardiac cycle), second (3.86 (2.06-6.91) mL/cardiac cycle) and third (7.79 (3.83-14.98) mL/cardiac cycle) trimesters (P < 0.001 for all). In accordance with the elevation in spiral artery distensibility, the median (IQR) ratio of serum PlGF/sFlt-1 × 103 levels increased between the first (7.2 (4.5-10.0)), second (22.7 (18.6-42.2)) and third (56.2 (41.9-92.5)) trimesters (P < 0.001 for all). The present study shows that B-flow/STIC M-mode ultrasonography provides an in-vivo imaging technology to quantify digitally the structural and physiological expansion of the walls of the spiral arteries during the cardiac cycle as a consequence of their transformation into compliant vessels during advancing stages of normal human pregnancy. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Prognostic Value of Resting Left Ventricular Sphericity Indexes in Coronary Artery Disease With Preserved Ejection Fraction.

Adverse left ventricular remodeling is a significant cardiovascular predictor for patients with coronary artery disease and preserved left ventricular ejection fraction (LVEF). However, the remodeling indexes reflecting left ventricular spherization by myocardial perfusion imaging are underexplored. 727 patients (mean age 59.8±13.5 years, 329 women) diagnosed or suspected coronary artery disease with preserved LVEF who underwent resting myocardial perfusion imaging were retrospectively enrolled. The myocardial perfusion imaging findings including the total perfusion deficit and sphericity indexes (shape index (SI) and eccentricity index (EI) obtained from gated (QGS) and non-gated (QPS) images) were collected. Major adverse cardiovascular events (MACE) were followed up for 45.1±22.0 months. All patients were divided into 4 subgroups based on total perfusion deficit at 10% and LVEF at 65%. Univariable comparative analyses were performed in 5 cohorts (all patients and 4 subgroups). Patients who experienced MACE displayed higher SI and/or lower EI (all P<0.05). Kaplan-Meier survival analyses suggested significant differences for SIQPS in all 5 cohorts, for EIQPS and EIQGS in 4 cohorts, and for end-systolic and end-diastolic SIQGS in 3 cohorts (allP<0.05). Multivariate Cox analysis showed that abnormal SI and EI remained statistically significant predictors for MACE after adjusting for total perfusion deficit, LVEF, and other confounding factors. For patients diagnosed or suspected of coronary artery disease with preserved or supra-normal LVEF, resting sphericity indexes by myocardial perfusion imaging displayed incremental long-term prognostic value. Among these indicators, SIQPS is particularly promising across different perfusion or preserved functional conditions.

Dilated lenticulostriate artery on whole-brain vessel wall imaging differentiates pathogenesis and predicts clinical outcomes in single subcortical infarction.

This study aimed to investigate the dilation of lenticulostriate artery (LSA) identified by whole-brain vessel wall imaging (WB-VWI) in differentiating the etiologic subtypes of single subcortical infarction (SSI) and to determine whether the appearance of dilated LSA was associated with 90-day clinical outcomes in parental atherosclerotic disease (PAD)-related SSI. Patients with acute SSI were prospectively enrolled and categorized into PAD-related SSI and cerebral small-vessel disease (CSVD)-related SSI groups. The imaging features of LSA morphology (branches, length, dilation, and tortuosity), plaques (burden, remodeling index, enhancement degree, and hyperintense plaque), and CSVD (white matter hyperintensity, lacunes, cerebral microbleed, and enlarged perivascular space) were evaluated. The logistic regression was performed to determine the association of dilated LSA with PAD-related SSI and 90-day clinical outcomes. In total, 131 patients (mean age, 52.2 ± 13.2 years; 99 men) were included. The multivariate logistic regression analysis revealed that the presence of dilated LSAs (odds ratio (OR), 7.40; 95% confidence interval (CI): 1.88-29.17; p = 0.004)) was significantly associated with PAD-related SSI. Moreover, after adjusting for confounding factors, the association of poor outcomes with the total length of LSAs (OR, 0.94; 95% CI: 0.90-0.99; p = 0.011), dilated LSAs (OR, 0.001; 95% CI: 0.0001-0.08; p = 0.002), and plaque burden (OR, 1.35; 95% CI: 1.11-1.63; p = 0.002) remained statistically significant. The dilation of LSA visualized on WB-VWI could differentiate various subtypes of SSI within LSA territory and was a prognostic imaging marker for 90-day clinical outcomes for PAD-related SSI. Evaluation of LSA morphology based on WB-VWI can differentiate the pathogenesis and predict clinical outcomes in SSI, providing crucial insights into the etiologic mechanisms, risk stratification, and tailored therapies for these patients. The prognosis of SSIs within lenticulostriate territory depend on the etiology of the disease. LSA dilation on WB-VWI was associated with parental atherosclerosis and better 90-day outcomes. Accurately identifying the etiology of SSIs in lenticulostriate territory assists in treatment decision-making.

High-resolution MR vessel wall imaging and cardiovascular health for evaluating the occurrence of ischemic stroke

ObjectivesTo explore the value of high-resolution MR vessel wall imaging (HR-VWI) based plaque characteristics combined with cardiovascular health (CVH) metrics in the risk evaluation of ischemic stroke attributed to middle cerebral artery (MCA) atherosclerotic stenosis. MethodsRetrospective analysis of 209 participants with middle cerebral atherosclerosis, 146 patients with high signal in the MCA area on DWI were included in the symptomatic group, and 63 patients were included in the asymptomatic group. The degree of stenosis, enhancement ratio, plaque burden, remodeling index, and intraplaque hemorrhage were measured and compared between groups. Seven CVH metrics and other clinical data were obtained. The association between these factors and ischemic stroke was investigated by univariate and multivariate analysis. ResultsThe degree of stenosis [OR, 1.036 (95 % CI, 1.014–1.058); P = 0.001], plaque burden [OR, 0.958 (95 % CI, 0.928–0.989); P = 0.009], intraplaque hemorrhage [OR, 3.530 (95 % CI, 1.233–10.110); P = 0.019], physical activity [OR, 4.321 (95 % CI, 1.526–12.231); P = 0.006], and diet [OR, 8.986 (95 % CI, 2.747–29.401); P < 0.001] were the independent characteristics associated with the occurrence of ischemic stroke. ROC curve showed that the combination of plaque characteristics, diet, and physical activity achieved the highest AUC of 0.828 (95 % CI 0.770–0.877; P < 0.001), with sensitivity and specificity being 86.30 % and 66.67 %, respectively. ConclusionPlaque characteristics combined with CVH metrics may identify high-risk populations for ischemic stroke and offer novel insights into risk evaluation and stratification.

Detectability of intracranial vessel wall atherosclerosis using black-blood spectral CT: a phantom and clinical study

BackgroundComputed tomography (CT) is the usual modality for diagnosing stroke, but conventional CT angiography reconstructions have limitations.MethodsA phantom with tubes of known diameters and wall thickness was scanned for wall detectability, wall thickness, and contrast-to-noise ratio (CNR) on conventional and spectral black-blood (SBB) images. The clinical study included 34 stroke patients. Diagnostic certainty and conspicuity of normal/abnormal intracranial vessels using SBB were compared to conventional. Sensitivity/specificity/accuracy of SBB and conventional were compared for plaque detectability. CNR of the wall/lumen and quantitative comparison of remodeling index, plaque burden, and eccentricity were obtained for SBB imaging and high-resolution magnetic resonance imaging (hrMRI).ResultsThe phantom study showed improved detectability of tube walls using SBB (108/108, 100% versus conventional 81/108, 75%, p < 0.001). CNRs were 75.9 ± 62.6 (mean ± standard deviation) for wall/lumen and 22.0 ± 17.1 for wall/water using SBB and 26.4 ± 15.3 and 101.6 ± 62.5 using conventional. Clinical study demonstrated (i) improved certainty and conspicuity of the vessels using SBB versus conventional (certainty, median score 3 versus 0; conspicuity, median score 3 versus 1 (p < 0.001)), (ii) improved sensitivity/specificity/accuracy of plaque (≥ 1.0 mm) detectability (0.944/0.981/0.962 versus 0.239/0.743/0.495) (p < 0.001), (iii) higher wall/lumen CNR of SBB of (78.3 ± 50.4/79.3 ± 96.7) versus hrMRI (18.9 ± 8.4/24.1 ± 14.1) (p < 0.001), and (iv) excellent reproducibility of remodeling index, plaque burden, and eccentricity using SBB versus hrMRI (intraclass correlation coefficient 0.85–0.94).ConclusionsSBB can enhance the detectability of intracranial plaques with an accuracy similar to that of hrMRI.Relevance statementThis new spectral black-blood technique for the detection and characterization of intracranial vessel atherosclerotic disease could be a time-saving and cost-effective diagnostic step for clinical stroke patients. It may also facilitate prevention strategies for atherosclerosis.Key points• Blooming artifacts can blur vessel wall morphology on conventional CT angiography.• Spectral black-blood (SBB) images are generated from material decomposition from spectral CT.• SBB images reduce blooming artifacts and noise and accurately detect small plaques.Graphical

Effect of colchicine on progression of known coronary atherosclerosis in patients with STable CoROnary artery disease CoMpared to placebo (EKSTROM) trial—rationale and design

BackgroundCardiovascular disease is the major cause of mortality in the United States. Despite lifestyle modification and traditional risk factor control residual inflammatory risk remains an untreated concern. Colchicine is an oral, medication that has been used for gout, mediterranean fever and pericarditis for decades. In recent trials, colchicine has been shown to reduce major adverse cardiovascular events, however the mechanism of benefit remains unclear. The objective of the randomized, double-blind, placebo controlled EKSTROM trial is to evaluate the effects of colchicine 0.5mg/day on atherosclerotic plaque. MethodsEighty-four participants will be enrolled after obtaining informed consent and followed for 12 months. Eligible patients will be randomly assigned to colchicine 0.5mg/day or placebo in a 1:1 fashion as add-on to their standard of care. All participants will undergo coronary computed tomography angiography (CCTA) at baseline and at 12 months. ResultsAs of November 2023, the study is 100% enrolled with an expected end of study by the second quarter of 2024. The primary endpoint is change in low attenuation plaque volume as measured by CCTA. Secondary endpoints include change in volume of different plaque types (including total atheroma volume, noncalcified plaque volume, dense calcified plaque volume, remodeling index), change in inflammatory markers (IL-6, IL-1β, IL-18, hs-CRP), change in pericoronary adipose tissue attenuation, change in epicardial adipose tissue volume and attenuation and change in brachial flow mediated dilation. ConclusionEKSTROM is the first randomized study to assess the effects of colchicine on plaque progression, pericoronary and epicardial fat. EKSTROM will provide important information on the mechanistic effects of colchicine on the cardiovascular system. Trial registrationRegistry: clinicaltrials.gov, Registration Number: NCT06342609 url: https://www.clinicaltrials.gov/study/NCT06342609?term=EKSTROM&rank=1

MRI-based adrenal gland volume is associated with cardiovascular alterations in individuals without prior cardiovascular disease

Aim of this study was to analyse the associations of cardiovascular health and adrenal gland volume as a rather new imaging biomarker of chronic hypothalamic–pituitary–adrenal (HPA) axis activation. The study population originates from the KORA population-based cross-sectional prospective cohort. 400 participants without known cardiovascular disease underwent a whole-body MRI. Manual segmentation of adrenal glands was performed on VIBE-Dixon gradient-echo sequence. MRI based evaluation of cardiac parameters was achieved semi-automatically. Cardiometabolic risk factors were obtained through standardized interviews and medical examination. Univariate and multivariate associations were derived. Bi-directional causal mediation analysis was performed. 351 participants were eligible for analysis (56 ± 9.1 years, male 58.7%). In multivariate analysis, significant associations were observed between adrenal gland volume and hypertension (outcome hypertension: Odds Ratio = 1.11, 95% CI [1.01, 1.21], p = 0.028), left ventricular remodelling index (LVRI) (outcome LVRI: β = 0.01, 95% CI [0.00, 0.02], p = 0.011), and left ventricular (LV) wall thickness (outcome LV wall thickness: β = 0.06, 95% CI [0.02, 0.09], p = 0.005). In bi-directional causal mediation analysis adrenal gland volume had a borderline significant mediating effect on the association between hypertension and LVRI (p = 0.052) as well as wall thickness (p = 0.054). MRI-based assessment of adrenal gland enlargement is associated with hypertension and LV remodelling. Adrenal gland volume may serve as an indirect cardiovascular imaging biomarker.