Coronary Sinus Metabolite 12,13-diHOME Is a Novel Biomarker for Left Atrial Remodeling in Patients With Atrial Fibrillation.

BACKGROUND: 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) has shown potential in protecting against heart disease, but its relationship with atrial fibrillation (AF) remains unknown. METHODS: Coronary sinus (CS) and femoral vein blood samplings were synchronously collected from AF and non-AF subjects (paroxysmal supraventricular tachycardia or idiopathic premature ventricular complexes) who underwent catheter ablation. First, untargeted metabolomic profiling was performed in a discovery cohort (including 12 AF and 12 non-AF subjects) to identify the most promising CS or femoral vein metabolite. Then, the selected metabolite was further measured in a validation cohort (including 119 AF and 103 non-AF subjects) to confirm its relationship with left atrium remodeling and 1-year postablation recurrence of AF. Finally, the biological function of the selected metabolite was validated in a rapid-paced cultured HL-1 atrial cardiomyocytes model. RESULTS: Metabolomic analysis identified CS 12,13-diHOME as the most pronounced change metabolite correlated with left atrium remodeling in the discovery cohort. In the validation cohort, CS 12,13-diHOME was significantly lower in patients with AF than non-AF controls (84.32±20.13 versus 96.24±23.56 pg/mL; P<0.01), and associated with worse structural, functional, and electrical remodeling of left atrium. Multivariable regression analyses further demonstrated that decreased CS 12,13-diHOME was an independent predictor of 1-year postablation recurrence of AF (odds ratio, 0.754 [95% CI, 0.648-0.920]; P=0.005). Biological function validations showed that 12,13-diHOME treatment significantly protect the cell viability, improved the expression of MHC (myosin heavy chain) and Cav1.2 (L-type calcium channel α1c), and attenuated mitochondrial damage in the rapid-paced cultured HL-1 cardiomyocytes model. CONCLUSIONS: CS metabolite 12,13-diHOME is decreased in patients with AF and can serve as a novel biomarker for left atrium remodeling.

Comparison of the 2005 Montreal Criteria and the 2019 Cirrhotic Cardiomyopathy Consortium Criteria for the Diagnosis of Cirrhotic Cardiomyopathy.

The comparison between the diagnostic criteria for cirrhotic cardiomyopathy (CCM) first proposed in 2005 (2005 Montreal criteria), and those redefined in the 2019 Cirrhotic Cardiomyopathy Consortium (2019 CCC criteria) has generated significant controversy. Importantly, the predictive value of these criteria in cirrhotic patients (CPs) remains unclear to this date. Thus, the present study aims to compare the 2 sets of criteria and investigate their predictive value in CPs. Between April 2021 and April 2023, a total of 104 CPs with an average age of 46.4 ± 8.9 years, who had no history of other cardiac diseases or malignancies were enrolled in this prospective single-center observational cohort study, conducted at the Third Affiliated Hospital of Sun Yat-Sen University. Various echocardiographic indicators were measured and assessed for their prognostic value and association with clinical outcomes. The prevalence of CCM was found to be comparable when evaluated using both the 2019 CCC and 2005 Montreal criteria (54.8% vs 44.2%, p = 0.161). However, the diagnosis of systolic dysfunction was significantly different between the 2 criteria (52.9% vs 1.0%, p <0.001). Among patients with systolic dysfunction, 27.9% had reduced left ventricular global longitudinal strain, while 25% had increased left ventricular global longitudinal strain. Moreover, fewer patients were diagnosed with diastolic dysfunction (DD) using the 2019 CCC criteria (4.8% vs 44.2%, p <0.001). Multivariate Cox analysis revealed that CPs who had encephalopathy, a high model for end-stage liver disease score, and DD diagnosed using the 2019 CCC criteria exhibited a poorer prognosis. In conclusion, although the prevalence of CCM according to both criteria is similar, the consistency is poor, indicating that they are not the same group of patients. Importantly, CPs with DD diagnosed according to the 2019 CCC criteria might be associated with increased adverse events.

Ultrasound Microvessel Visualization in Cervical Cancer: Association Between Novel Ultrasound Techniques and Histologic Microvessel Densities.

OBJECTIVE: The aim of the work described here was to evaluate the feasibility of superb microvascular imaging (SMI) and vascular endothelial growth factor receptor 2 (VEGFR2)-targeted microbubble (MBVEGFR2)-based ultrasound molecular imaging (USMI) for visualizing microvessels in cervical cancer. METHODS: Hela cells were used to establish subcutaneous cervical cancer models. SMI and MBVEGFR2-based USMI were performed, and the results were compared with intratumoral microvessel density (MVD) in four groups based on tumor diameter (<3 mm, 3-5 mm, 5-7 mm and ≥7 mm). The vascularization index (VI, %) was evaluated for SMI, and the normalized intensity difference (NID) for USMI. RESULTS: Tumors with diameters ranging from 3 to 5 mm had the highest VI (39.07 ± 1.58) in SMI, and VI significantly decreased with increasing tumor size (all p values <0.001). The strongest signal intensity was observed in very early tumors (d < 3 mm: 43.80 ± 3.58%) after MBVEGFR2 administration; the NID gradually decreased with increasing diameter of tumors (all p values = 0.007). However, no significant differences were observed in NID after administration of non-targeted (control) microbubbles (MBCon) (all p values = 0.125). MBVEGFR2-based USMI had the strongest correlation with MVD in displaying microvessels of cervical cancer compared with SMI and MBCon (R2 = 0.78 vs. R2 = 0.40 and R2 = 0.38). CONCLUSION: These findings validate the superiority and accuracy of MBVEGFR2-based USMI for microvessel imaging and monitoring of angiogenesis in cervical cancer compared with SMI and MBCon. Nonetheless, SMI remains an alternative to microvessel imaging when ultrasonic contrast agent use is contraindicated.

VEGFR2 targeted microbubble-based ultrasound molecular imaging improving the diagnostic sensitivity of microinvasive cervical cancer.

BACKGROUND: The current diagnostic methods of microinvasive cervical cancer lesions are imaging diagnosis and pathological evaluation. Pathological evaluation is invasive and imaging approaches are of extremely low diagnostic performance. There is a paucity of effective and noninvasive imaging approaches for these extremely early cervical cancer during clinical practice. In recent years, ultrasound molecular imaging (USMI) with vascular endothelial growth factor receptor type 2 (VEGFR2) targeted microbubble (MBVEGFR2) has been reported to improve the early diagnosis rates of breast cancer (including ductal carcinoma in situ), pancreatic cancer and hepatic micrometastases. Herein, we aimed to assess the feasibility of MBVEGFR2-based USMI in extremely early cervical cancer detection to provide an accurate imaging modality for microinvasive cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) Stage IA1 and IA2). RESULTS: We found MBVEGFR2-based USMI could successfully distinguish extremely early lesions in diameter < 3 mm from surrounding normal tissues (all P < 0.05), and the sensitivity gradually decreased along with increasing tumor diameter. Moreover, normalized intensity difference (NID) values showed a good linear correlation with microvessel density (MVD) (R2 = 0.75). In addition, all tumors could not be identified from surrounding muscles in subtracted ultrasound images when mice were administered MBCon. CONCLUSIONS: Overall, MBVEGFR2-based USMI has huge potential for clinical application for the early detection of microinvasive cervical cancer (FIGO Stage IA1 and IA2), providing the foothold for future studies on the imaging screening of this patient population.

Deep learning based on carotid transverse B-mode scan videos for the diagnosis of carotid plaque: a prospective multicenter study.

OBJECTIVES: Accurate detection of carotid plaque using ultrasound (US) is essential for preventing stroke. However, the diagnostic performance of junior radiologists (with approximately 1 year of experience in carotid US evaluation) is relatively poor. We thus aim to develop a deep learning (DL) model based on US videos to improve junior radiologists' performance in plaque detection. METHODS: This multicenter prospective study was conducted at five hospitals. CaroNet-Dynamic automatically detected carotid plaque from carotid transverse US videos allowing clinical detection. Model performance was evaluated using expert annotations (with more than 10 years of experience in carotid US evaluation) as the ground truth. Model robustness was investigated on different plaque characteristics and US scanning systems. Furthermore, its clinical applicability was evaluated by comparing the junior radiologists' diagnoses with and without DL-model assistance. RESULTS: A total of 1647 videos from 825 patients were evaluated. The DL model yielded high performance with sensitivities of 87.03% and 94.17%, specificities of 82.07% and 74.04%, and areas under the receiver operating characteristic curve of 0.845 and 0.841 on the internal and multicenter external test sets, respectively. Moreover, no significant difference in performance was noted among different plaque characteristics and scanning systems. Using the DL model, the performance of the junior radiologists improved significantly, especially in terms of sensitivity (largest increase from 46.3 to 94.44%). CONCLUSIONS: The DL model based on US videos corresponding to real examinations showed robust performance for plaque detection and significantly improved the diagnostic performance of junior radiologists. KEY POINTS: • The deep learning model based on US videos conforming to real examinations showed robust performance for plaque detection. • Computer-aided diagnosis can significantly improve the diagnostic performance of junior radiologists in clinical practice.

Association between serum cystatin C and early impairment of cardiac function and structure in type 2 diabetes patients with normal renal function.

BACKGROUND: Type 2 diabetes mellitus (T2DM) patients may have cardiac remodeling and dysfunction from the early stage of disease. This study aimed to determine the association between cystatin C (CysC) and early cardiac functional or structural impairment in T2DM patients without renal dysfunction. METHODS: A total of 1135 T2DM patients without renal dysfunction and known heart diseases were included in our study. Cardiac function and structure were evaluated by echocardiography. Patients were diagnosed as left ventricular hypertrophy (LVH), impaired left ventricular (LV) diastolic function, and categorized into four different LV geometry patterns including normal, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. RESULTS: In multivariate linear regression analyses, CysC was positively associated with interventricular septum, LV mass index, left atrial volume index, E/e' ratio, and negatively associated with Tissue Doppler e', E/A ratio (p < .05). As a continuous variable, increasing CysC levels were associated with prevalence of LVH (OR: 1.47, 95% confidence interval [CI]: 1.22-1.77), impaired LV diastolic function (OR: 1.58, 95% CI: 1.33-1.87), concentric hypertrophy (OR: 1.54, 95% CI: 1.23-1.93) and eccentric hypertrophy (OR: 1.34, 95% CI: 1.00-1.80) according to multivariate logistic regression analyses. While as a categorical variable, the highest CysC quartile (CysC > 1.04 mg/L) was associated with LVH (OR: 2.95, 95% CI: 1.74-5.00), impaired LV diastolic function (OR: 4.09, 95% CI: 2.54-6.60), and concentric hypertrophy (OR: 3.26, 95% CI: 2.05-5.18). CONCLUSIONS: CysC was significantly associated with early LV remodeling and cardiac functional impairment in T2DM patients with normal renal function. It could be a reliable and convenient biomarker detecting early impairment of cardiac function and structure in T2DM patients.

Redistribution of adipose tissue is associated with left atrial remodeling and dysfunction in patients with atrial fibrillation.

Objective: Adipose tissue is recognized as a crucial regulator of atrial fibrillation (AF). However, the effect of epicardial adipose tissue (EAT) on the pathophysiology of AF might be different from that of other adipose tissues. The purpose of this study was to explore the distribution features of different adipose tissues in AF patients and their relationships with left atrial (LA) remodeling and function. Methods: A total of 205 participants (including 112 AF and 93 non-AF patients) were recruited. Color doppler ultrasound was used to measure the thickness of subcutaneous, extraperitoneal, and intra-abdominal adipose tissue. Cardiac CT scan was performed to measure the mean thickness of EAT surrounding the whole heart (total-EAT) and specific regions, including left atrium (LA-EAT), left ventricle, right ventricle, interventricular groove, and atrioventricular groove. LA anatomical remodeling and function were measured by echocardiography, while electrical remodeling was evaluated by P-wave duration and dispersion using Electrocardiography (obtained after cardioversion or ablation in AF patients). Relationship between the thickness of different adipose tissues and LA remodeling and function was analyzed. Results: The thickness of subcutaneous, extraperitoneal, and intra-abdominal adipose tissue was similar between AF and non-AF patients, and had no or only weak association with LA remodeling and dysfunction. However, compared to non-AF participants, total-EAT thickness significantly increased in both paroxysmal and persistent AF patients (non-AF vs. paroxysmal AF vs. persistent AF: 6.31 ± 0.63 mm vs. 6.76 ± 0.79 mm vs. 7.01 ± 1.18 mm, P < 0.001), which was positively correlated with the LA size and P-wave duration and dispersion, and negatively correlated with LA ejection fraction and peak strain rate. More interestingly, EAT thickness in AF patients did not increase uniformly in different regions of the heart. Compared to EAT surrounding the other regions, LA-EAT was found to accumulate more greatly, and had a closer relationship to LA remodeling and dysfunction. Multivariate logistic regression analysis also showed that LA-EAT was significantly correlated with the presence of AF (OR = 4.781; 95% CI 2.589-8.831, P < 0.001). Conclusion: Rather than other adipose tissues, accumulation and redistribution of EAT, especially surrounding the LA, is associated with LA remodeling and dysfunction in AF patients.

Monocyte to High-Density Lipoprotein Cholesterol Ratio Is Associated with Subclinical Left Cardiac Remodeling and Dysfunction in Type 2 Diabetes Mellitus.

Chronic inflammation is involved in the development of heart failure (HF) in type 2 diabetes mellitus (T2DM). However, reliable and easily accessible biomarker of subclinical left cardiac remodeling and dysfunction remains a challenge.Overall, 1020 patients with T2DM without overt HF were enrolled from May 2019 to April 2020. Monocyte to high-density lipoprotein ratio (MHR) was calculated by blood monocyte count divided by high-density lipoprotein cholesterol. Left cardiac structure and function were assessed using transthoracic echocardiography. Univariate and multivariate linear regression analyses were used to estimate the association of MHR (Lg transferred) with echocardiographic parameters. We found that septal wall thickness (SWT), left ventricular internal end-diastole dimension (LVIDd), and left ventricular mass index (LVMI) raised with increasing MHR (P = 0.002 for SWT, P < 0.001 for LVIDd, and P = 0.001 for LVMI). Declined trends were shown in ejection fraction (EF) (P = 0.016), E velocity (P = 0.037), E/A ratio (P = 0.009), and tissue Doppler e' (P < 0.001), and elevating trend was observed in E/e' (P < 0.001). In multivariate regression analysis, MHR (Lg transferred) was positively associated with LVIDd (ß = 0.031; P = 0.016), LVMI (ß = 0.073; P = 0.014), and E/e' (ß = 0.331; P < 0.001), whereas it was negatively associated with EF (ß = -0.086; P = 0.007), E/A (ß = -0.072; P = 0.009), and e' (ß = -0.332; P < 0.001).MHR could be a practical biomarker for indicating subclinical cardiac remodeling and dysfunction in T2DM, due to low cost and easy availability.

Impact of long-term glucose variability on coronary atherosclerosis progression in patients with type 2 diabetes: a 2.3 year follow-up study.

BACKGROUND: Glycemic variability (GV) confers a risk of cardiovascular events. In this study, we aimed to investigate whether long-term GV has an impact on coronary atherosclerosis progression in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 396 patients with T2DM who had coronary computed tomography angiography and laboratory data available at baseline and for follow-up evaluations [median 2.3 (1.8-3.1) years] were included. Fasting plasma glucose (FPG) was measured every 1-3 months, and HbA1c was measured quarterly. The coefficient of variation (CV) of HbA1c and FPG were calculated as measures of GV. Quantitative assessment of coronary plaques was performed by measuring the annual change and progression rate of total plaque volume (TPV). Significant progression was defined as annual TPV progression ≥ 15%. Multivariable regression analyses were used to assess the effects of GV on atherosclerosis progression. RESULTS: In the 396 patients, the annual change in TPV was 12.35 ± 14.23 mm3, and annual progression rate was 13.36 ± 12.69%. There were 143 (36.11%) patients with significant progression, and they had a significantly higher CV-HbA1c (P < 0.001) and CV-FPG (P < 0.001) than those without significant progression. In multivariable regression analyses, both CV-HbA1c and CV-FPG were independent predictors of annual change in TPV [CV-HbA1c: ß = 0.241 (0.019-0.462), P = 0.034; CV-FPG: ß = 0.265 (0.060-0.465), P = 0.012], annual TPV progression [CV-HbA1c: ß = 0.214 (0.023-0.405), P = 0.029; CV-FPG: ß = 0.218 (0.037-0.399), P = 0.019], and significant atherosclerosis progression [CV-HbA1c: odds ratio [OR] = 1.367 (1.149-1.650), P = 0.010; CV-FPG: OR = 1.321 (1.127-1.634), P = 0.013]. CONCLUSIONS: Long-term GV is associated with accelerated progression of coronary atherosclerosis independent of conventional risk factors in patients with T2DM. Trial registration ClinicalTrials.gov (NCT02587741), October 27, 2015; retrospectively registered.

Impact of HbA1c variability on subclinical left ventricular remodeling and dysfunction in patients with type 2 diabetes mellitus.

BACKGROUND: Glycemic instability confers a risk of poor prognosis in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate whether HbA1c variability provided additional value over mean HbA1c for predicting subclinical left ventricular remodeling and dysfunction in T2DM patients. METHODS: A total of 466 T2DM patients with normal cardiac structure and function were recruited and prospectively followed up for a median of 4.7 y. HbA1c was measured quarterly. The intrapersonal mean and standard deviation (SD) of HbA1c measurements were calculated, and SD-HbA1c was considered as a measure of HbA1c variability. All participants underwent transthoracic echocardiography at baseline and after follow-up. RESULTS: In multivariable regression analyses, SD-HbA1c was independently associated with annualized changes in left ventricular end diastolic diameter, interventricular septum, left ventricular posterior wall, left ventricular mass index, left ventricular ejection fraction, E/e' ratio, and E/A ratio (P < 0.001). Subgroup analysis based on mean HbA1c levels (<7.0%, 7.0-7.5%, and ≥7.5%) further confirmed that SD-HbA1c was associated with most of the above parameters regardless of mean HbA1c levels. CONCLUSION: This study indicates that HbA1c variability adds to the mean value in predicting subclinical left ventricular remodeling and dysfunction in T2DM patients.

Visit-to-visit fasting plasma glucose variability is an important risk factor for long-term changes in left cardiac structure and function in patients with type 2 diabetes.

BACKGROUND: To investigate the effect of visit-to-visit fasting plasma glucose (FPG) variability on the left cardiac structure and function in patients with type 2 diabetes mellitus (T2DM). METHODS: In this prospective cohort study, 455 T2DM patients were included and follow-up for a median of 4.7 years. FPG measured on every hospital visit was collected. FPG variability was calculated by its coefficient of variation (CV-FPG). Left cardiac structure and function were assessed using echocardiography at baseline and after follow-up. Multivariable linear regression analyses were used to estimate the effect of FPG variability on the annualized changes in left cardiac structure and function. Subgroup analysis stratified by mean HbA1c levels (< 7% and ≥ 7%) were also performed. RESULT: In multivariable regression analyses, CV-FPG was independently associated with the annualized changes in left ventricle (ß = 0.137; P = 0.031), interventricular septum (ß = 0.215; P = 0.001), left ventricular posterior wall thickness (ß = 0.129; P = 0.048), left ventricular mass index (ß = 0.227; P < 0.001), and left ventricular ejection fraction (ß = - 0.132; P = 0.030). After additionally stratified by mean HbA1c levels, CV-FPG was still independently associated with the annualized changes in the above parameters in patients with HbA1c ≥ 7%, while not in patients with HbA1c < 7%. CONCLUSIONS: Visit-to-visit variability in FPG could be a novel risk factor for the long-term adverse changes in left cardiac structure and systolic function in patients with type 2 diabetes. Trial registration ClinicalTrials.gov (NCT02587741), October 27, 2015, retrospectively registered.

Contrast-Enhanced Ultrasonography Versus Contrast-Enhanced Computed Tomography for Assessment of Residual Tumor From Hepatocellular Carcinoma Treated With Transarterial Chemoembolization: A Meta-analysis.

OBJECTIVES: This study reviewed the literature to directly evaluate the diagnostic performance of contrast-enhanced ultrasonography (CEUS) versus contrast-enhanced computed tomography (CECT) for assessing residual tumors of hepatocellular carcinoma treated with transarterial chemoembolization. METHODS: PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure were searched through April 30, 2017. The pooled sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristic curve were calculated and compared to examine the diagnostic performance of CEUS versus CECT. RESULTS: A total of 11 studies, including 421 patients and 491 nodules were analyzed. The pooled diagnostic performances of CEUS versus CECT were as follows: (1) sensitivity (95% confidence interval), 0.97 (0.95-0.99) versus 0.72 (0.67-0.76); (2) specificity, 0.86 (0.74-0.94) versus 0.99 (0.95-1.00); (3) positive predictive value, 0.97 (0.95-0.99) versus 1.00 (0.98-1.00); (4) negative predictive value, 0.90 (0.83-0.95) versus 0.51 (0.44-0.58); (5) positive likelihood ratio, 7.79 (4.73-12.82) versus 12.50 (5.74-27.20); (6) negative likelihood ratio, 0.05 (0.03-0.09) versus 0.35 (0.26-0.48); (7) diagnostic odds ratio, 150.56 (57.03-397.49) versus 35.54 (14.89-84.83); and (8) area under the summary receiver operating characteristic curve, 0.9875 versus 0.9239. The sensitivity and negative predictive value of CEUS were significantly higher than those of CECT (both P < .001). The specificity and positive predictive value of CECT were significantly higher than those of CEUS (both P < .05). CONCLUSIONS: Contrast-enhanced US, with better sensitivity and negative predictive value versus CECT, was an effective method for exclusion of residual tumors after transarterial chemoembolization. Contrast-enhanced CT, with higher specificity than CEUS, is a valid approach for identifying residual tumors.