Insights into the toxicological effects of nanomaterials on atherosclerosis: mechanisms involved and influence factors.

Atherosclerosis is one of the most common types of cardiovascular disease and is driven by lipid accumulation and chronic inflammation in the arteries, which leads to stenosis and thrombosis. Researchers have been working to design multifunctional nanomedicines with the ability to target, diagnose, and treat atherosclerosis, but recent studies have also identified that nanomaterials can cause atherosclerosis. Therefore, this review aims to outline the molecular mechanisms and physicochemical properties of nanomaterials that promote atherosclerosis. By analyzing the toxicological effects of nanomaterials on cells involved in the pathogenesis of atherosclerosis such as vascular endothelial cells, vascular smooth muscle cells and immune cells, we aim to provide new perspectives for the prevention and treatment of atherosclerosis, and raise awareness of nanotoxicology to advance the clinical translation and sustainable development of nanomaterials.

Deep learning-based automated left ventricular ejection fraction assessment using 2-D echocardiography.

Deep learning (DL) has been applied for automatic left ventricle (LV) ejection fraction (EF) measurement, but the diagnostic performance was rarely evaluated for various phenotypes of heart disease. This study aims to evaluate a new DL algorithm for automated LVEF measurement using two-dimensional echocardiography (2DE) images collected from three centers. The impact of three ultrasound machines and three phenotypes of heart diseases on the automatic LVEF measurement was evaluated. Using 36890 frames of 2DE from 340 patients, we developed a DL algorithm based on U-Net (DPS-Net) and the biplane Simpson's method was applied for LVEF calculation. Results showed a high performance in LV segmentation and LVEF measurement across phenotypes and echo systems by using DPS-Net. Good performance was obtained for LV segmentation when DPS-Net was tested on the CAMUS data set (Dice coefficient of 0.932 and 0.928 for ED and ES). Better performance of LV segmentation in study-wise evaluation was observed by comparing the DPS-Net v2 to the EchoNet-dynamic algorithm (P = 0.008). DPS-Net was associated with high correlations and good agreements for the LVEF measurement. High diagnostic performance was obtained that the area under receiver operator characteristic curve was 0.974, 0.948, 0.968, and 0.972 for normal hearts and disease phenotypes including atrial fibrillation, hypertrophic cardiomyopathy, dilated cardiomyopathy, respectively. High performance was obtained by using DPS-Net in LV detection and LVEF measurement for heart failure with several phenotypes. High performance was observed in a large-scale dataset, suggesting that the DPS-Net was highly adaptive across different echocardiographic systems.NEW & NOTEWORTHY A new strategy of feature extraction and fusion could enhance the accuracy of automatic LVEF assessment based on multiview 2-D echocardiographic sequences. High diagnostic performance for the determination of heart failure was obtained by using DPS-Net in cases with different phenotypes of heart diseases. High performance for left ventricle segmentation was obtained by using DPS-Net, suggesting the potential for a wider range of application in the interpretation of 2DE images.

DAPSA, carotid plaque and cardiovascular events in psoriatic arthritis: a longitudinal study.

OBJECTIVE: To examine whether Disease Activity in Psoriatic Arthritis (DAPSA) reflecting the inflammatory component of psoriatic arthritis (PsA) can predict cardiovascular (CV) events independent of traditional CV risk factors and subclinical carotid atherosclerosis. METHODS: A cohort analysis was performed in patients with PsA who had been followed since 2006. The outcome of interest was first CV event. Four different CV disease (CVD) risk scores and DAPSA were computed at baseline. The presence of carotid plaque (CP) and carotid intima-media thickness (CIMT) was also determined in a subgroup of patients using high-resolution ultrasound. The association between DAPSA, CVD risk scores, CP, CIMT and the occurrence of CV events was assessed using Cox proportional hazard models. RESULTS: 189 patients with PsA (mean age: 48.9 years; male: 104 (55.0%)) were recruited. After a median follow-up of 9.9 years, 27 (14.3%) patients developed a CV event. Higher DAPSA was significantly associated with an increased risk of developing CV events (HR: 1.04, 95% CI (1.01 to 1.08), p=0.009). The association remained significant after adjusting for all CV risk scores in the multivariable models. In the subgroup analysis, 154 patients underwent carotid ultrasound assessment and 23 (14.9%) of them experienced a CV event. CP was associated with increased risk of developing CV events after adjusting for three CV risk scores and DAPSA, with HR ranging from 2.35 to 3.42. CONCLUSION: Higher DAPSA and the presence of CP could independently predict CVD events in addition to traditional CV risk scores in patients with PsA.

Electrocardiographic evidence of abnormal atrial phenotype in Brugada syndrome.

BACKGROUND: Brugada syndrome (BrS) is an inherited ion channelopathy that may predispose affected individuals to atrial cardiomyopathy. We tested the hypothesis that BrS patients have higher degrees of atrial electrophysiological abnormalities compared to controls, and these can be reflected by changes in P-wave parameters determined on the electrocardiogram (ECG). METHODS: This was a single-center retrospective study comparing BrS patients to age- and gender-matched control subjects. Mean P-wave duration (PWDmean), maximum PWD (PWDmax) and minimum PWD (PWDmin), P-wave dispersion (PWDmax - PWDmin), and P-wave terminal force in V1 (PTFV1) were measured. PWDmax ≥ 120 ms, in the presence and absence of biphasic P-waves in the inferior leads, were termed advanced and partial inter-atrial block (IAB), respectively. RESULTS: The proportion of IAB was significantly higher in BrS patients (28/51; 55%) than in control subjects (14/51; 27%; Fisher's Exact test; P < 0.01). Advanced IAB was observed in two BrS patients but none of the control subjects (P = 0.50). Compared to controls, BrS patients showed higher PWDmean (107 [98-113] vs. 97 [90-108] ms; KWANOVA, P < 0.01), PWDmax (123 [110-132] vs. 113 [107-121] ms; P < 0.001) but statistically indistinguishable PWDmin (82 [72-92] vs. 77 [69-85]; P = 0.09), and P-wave dispersion (38 [26-52] vs. 37 [23-45] ms; P = 0.14). PTFV1 was significantly higher in BrS patients than in control subjects (24 [0-40] vs. 0 [0-27] mm.ms; P < 0.05). CONCLUSION: Atrial conduction abnormalities are frequently observed in BrS. These patients may require monitoring for future development of atrial fibrillation and stroke.

Genotype-guided warfarin dosing vs. conventional dosing strategies: a systematic review and meta-analysis of randomized controlled trials.

AIMS: Previous trials on the effectiveness of genotype-guided warfarin dosing vs. conventional dosing have been inconclusive. We conducted a systematic review and meta-analysis of randomized trials comparing genotype-guided to conventional dosing strategies. METHODS: PubMed and the Cochrane Library were searched up to 23 October 2017. RESULTS: A total of 76 and 94 entries were retrieved were retrieved from PubMed and the Cochrane Library, respectively. A total of 2626 subjects in the genotype-guided dosing (mean age 63.3 ± 5.8 years; 46% male) and 2604 subjects in the conventional dosing (mean age 64.7 ± 6.1 years; 46% male) groups (mean follow-up duration 64 days) from 18 trials were included. Compared with conventional dosing, genotype-guided dosing significantly shortened the time to first therapeutic international normalized ratio (INR) (mean difference 2.6 days, standard error 0.3 days; P < 0.0001; I2 0%) and time to first stable INR (mean difference 5.9 days, standard error 2.0 days; P < 0.01; I2 94%). Genotype-guided dosing also increased the time in therapeutic range (mean difference 3.1%, standard error 1.2%; P < 0.01; I2 80%) and reduced the risks of both excessive anticoagulation, defined as INR ≥4 [risk ratio (RR) 0.87; 95% confidence interval (CI) 0.78, 0.98; P < 0.05; I2 : 0%), and bleeding (RR 0.82; 95% CI 0.69, 0.98; P < 0.05; I2 31%). No difference in thromboembolism (RR 0.84; 95% CI 0.56, 1.26; P = 0.40; I2 0%) or mortality (RR 1.16; 95% CI 0.46, 2.91; P = 0.76; I2 0%) was observed between the two groups. CONCLUSIONS: Genotype-guided warfarin dosing offers better safety with less bleeding compared with conventional dosing strategies. No significant benefit on thromboembolism or mortality was evident.

Quantitative analysis of mitral valve morphology in atrial functional mitral regurgitation using real-time 3-dimensional echocardiography atrial functional mitral regurgitation.

BACKGROUND: Atrial fibrillation (AF) can result in atrial functional mitral regurgitation (MR), but the mechanism remains controversial. Few data about the relationship between the 3-dimensional morphology of the MV and the degree of MR in AF exist. METHODS: Real-time 3-dimensional transesophageal echocardiography (3D-TEE) of the MV was acquired in 168 patients with AF (57.7% persistent AF), including 25 (14.9%) patients with moderate to severe MR (the MR+ group) and 25 patients without AF as controls. The 3-dimensional geometry of the MV apparatus was acquired using dedicated quantification software. RESULTS: Compared with the group of patients with no or mild MR (the MR- group) and the controls, the MR+ group had a larger left atrium (LA), a more dilated mitral annulus (MA), a reduced annular height to commissural width ratio (AHCWR), indicating flattening of the annular saddle shape, and greater leaflet surfaces and tethering. MR severity was correlated with the MA area (r2 = 0.43, P < 0.01) and the annulus circumference (r2 = 0.38, P < 0.01). A logistic regression analysis indicated that the MA area (OR: 1.02, 95% CI: 1.01-1.03, P < 0.01), AHCWR (OR: 0.24, 95% CI: 0.14-0.35, P = 0.04) and MV tenting volume (OR: 3.24, 95% CI: 1.16-9.08, P = 0.03) were independent predictors of MR severity in AF patients. CONCLUSIONS: The mechanisms of "atrial functional MR" are complex and include dilation of the MA, flattening of the annular saddle shape and greater leaflet tethering.

Increased prevalence of coronary plaque in patients with psoriatic arthritis without prior diagnosis of coronary artery disease.

OBJECTIVES: To evaluate coronary atherosclerosis in patients with psoriatic arthritis (PsA) and control subjects using coronary CT angiography (CCTA). METHODS: Ninety consecutive patients with PsA (male: 56(62.2%); 50.3±11.1 years) were recruited. 240 controls (male: 137(57.1%); 49.6±10.7 years) without known cardiovascular (CV) diseases who underwent CCTA due to chest pain and/or multiple CV risk factors were recruited for comparison. RESULTS: Patients with PsA and controls were matched in age, gender and traditional CV risk factors (all p>0.2). The prevalence of overall plaque (54(60%)/84(35%), p<0.001), calcified plaque (CP) (29(32%)/40(17%), p=0.002), mixed plaque (MP) (20(22%)/18(8%), p<0.001), non-calcified plaque (NCP) (39(43%)/53(22%), p<0.001) and combined MP/NCP (46(51%)/62(26%), p<0.001) were all significantly higher in patients with PsA. Three-vessel disease was diagnosed in 12(13%) patients with PsA and 7(3%) controls (p<0.001), while obstructive plaques (>50% stenosis) were observed in 8(9%) patients with PsA and 7(3%) controls (p=0.033). After adjusting for traditional CV risk factors, PsA remained an independent explanatory variable for all types of coronary plaques (OR: 2.730 to 4.064, all p<0.001). PsA was also an independent explanatory variable for three-vessel disease (OR: 10.798, p<0.001) and obstructive plaque (3.939, p=0.024). In patients with PsA, disease duration was the only disease-specific characteristic associated with more vulnerable plaques (MP/NCP) in multivariate analysis (1.063, p=0.031). The other independent explanatory variables were age ≥55 years (5.636, p=0.005) and male gender (8.197, p=0.001). CONCLUSIONS: Patients with PsA have increased prevalence, burden and severity of coronary atherosclerosis as documented by CCTA. Longer disease duration was independently associated with the presence of vulnerable MP/NCP plaques in patients with PsA. TRIAL REGISTRATION NUMBER: NCT02232321.

Quantitative analysis of mitral valve morphology in mitral valve prolapse with real-time 3-dimensional echocardiography: importance of annular saddle shape in the pathogenesis of mitral regurgitation.

BACKGROUND: Few data exist on the relation of the 3-dimensional morphology of mitral valve and degree of mitral regurgitation (MR) in mitral valve prolapse. METHODS AND RESULTS: Real-time 3-dimensional transesophageal echocardiography of the mitral valve was acquired in 112 subjects, including 36 patients with mitral valve prolapse and significant MR (≥3+; MR+ group), 32 patients with mitral valve prolapse but no or mild MR (≤2+; MR- group), 12 patients with significant MR resulting from nonprolapse pathologies (nonprolapse group), and 32 control subjects. The 3-dimensional geometry of mitral valve apparatus was measured with dedicated quantification software. Compared with the normal and MR- groups, the MR+ group had more dilated mitral annulus (P<0.0001), a reduced annular height to commissural width ratio (AHCWR) (P<0.0001) indicating flattening of annular saddle shape, redundant leaflet surfaces (P<0.0001), greater leaflet billow volume (P<0.0001) and billow height (P<0.0001), longer lengths from papillary muscles to coaptation (P<0.0001), and more frequent chordal rupture (P<0.0001). Prevalence of chordal rupture increased progressively with annulus flattening (7% versus 24% versus 42% for AHCWR >20%, 15%-20%, and <15%, respectively; P=0.004). Leaflet billow volume increased exponentially with decreasing AHCWR in patients without chordal rupture (r(2)=0.66, P<0.0001). MR severity correlated strongly with leaflet billow volume (r(2)=0.74, P<0.0001) and inversely with AHCWR (r(2)=0.44, P<0.0001). In contrast, annulus dilatation but not flattening occurred in nonprolapse MR patients. An AHCWR <15% (odds ratio=7.1; P=0.0004) was strongly associated with significant MR in mitral valve prolapse. CONCLUSION: Flattening of the annular saddle shape is associated with progressive leaflet billowing and increased frequencies of chordal rupture and may be important in the pathogenesis of MR in mitral valve prolapse.

Left atrial function in heart failure with impaired and preserved ejection fraction.

PURPOSE OF REVIEW: Left atrial structural and functional changes in heart failure are relatively ignored parts of cardiac assessment. This review illustrates the pathophysiological and functional changes in left atrium in heart failure as well as their prognostic value. RECENT FINDINGS: Heart failure can be divided into those with systolic dysfunction and heart failure with preserved ejection fraction (HFPEF). Left atrial enlargement and dysfunction commonly occur in systolic heart failure, in particular, in idiopathic dilated cardiomyopathy. Atrial enlargement and dysfunction also carry important prognostic value in systolic heart failure, independently of known parameters such as left ventricular ejection fraction. In HFPEF, there is evidence of left atrial enlargement, impaired atrial compliance, and reduction of atrial pump function. This occurs not only at rest but also during exercise, indicating significant impairment of atrial contractile reserve. Furthermore, atrial dyssynchrony is common in HFPEF. These factors further contribute to the development of new onset or progression of atrial arrhythmias, in particular, atrial fibrillation. SUMMARY: Left atrial function is an integral part of cardiac function and its structural and functional changes in heart failure are common. As changes of left atrial structure and function have different clinical implications in systolic heart failure and HFPEF, routine assessment is warranted.

Quantification of mitral valve morphology with three-dimensional echocardiography--can measurement lead to better management?

The mitral valve (MV) has complex 3-dimensional (3D) morphology and motion. Advance in real-time 3D echocardiography (RT3DE) has revolutionized clinical imaging of the MV by providing clinicians with realistic visualization of the valve. Thus far, RT3DE of the MV structure and dynamics has adopted an approach that depends largely on subjective and qualitative interpretation of the 3D images of the valve, rather than objective and reproducible measurement. RT3DE combined with image-processing computer techniques provides precise segmentation and reliable quantification of the complex 3D morphology and rapid motion of the MV. This new approach to imaging may provide additional quantitative descriptions that are useful in diagnostic and therapeutic decision-making. Quantitative analysis of the MV using RT3DE has increased our understanding of the pathologic mechanism of degenerative, ischemic, functional, and rheumatic MV disease. Most recently, 3D morphologic quantification has entered into clinical use to provide more accurate diagnosis of MV disease and for planning surgery and transcatheter interventions. Current limitations of this quantitative approach to MV imaging include labor-intensiveness during image segmentation and lack of a clear definition of the clinical significance of many of the morphologic parameters. This review summarizes the current development and applications of quantitative analysis of the MV morphology using RT3DE.

Incremental value of global systolic dyssynchrony in determining the occurrence of functional mitral regurgitation in patients with left ventricular systolic dysfunction.

AIMS: The aim of this study was to assess the contribution of left ventricular (LV) systolic dyssynchrony to functional mitral regurgitation (MR). METHODS AND RESULTS: Patients (n = 136) with LV systolic dysfunction (ejection fraction <50%) and at least mild MR were prospectively recruited. The effective regurgitant orifice area (EROA) was assessed by the proximal isovelocity surface area method. Left ventricular global systolic dyssynchrony [the maximal difference in time to peak systolic velocity among the 12 LV segments (Ts-Dif)] and regional systolic dyssynchrony (the delay between the anterolateral and posteromedial papillary muscle attaching sites) were assessed by tissue Doppler imaging. Left ventricular global and regional remodelling, systolic function, indices of mitral valvular and annular deformation were also measured. The size of the EROA correlated with the degrees of mitral deformation, LV remodelling, systolic function, and systolic dyssynchrony. By multivariate logistic regression analysis, the mitral valve tenting area (OR = 1.020, P < 0.001) and the Ts-Dif (OR = 1.011, P = 0.034) were independent determinants of significant functional MR (defined by EROA ≥20 mm(2)). From the receiver-operating characteristic curve, the tenting area of 2.7 cm(2) (sensitivity 83%, specificity 82%, AUC 0.86, P < 0.001) and the Ts-Dif of 85 ms (sensitivity 66%, specificity 72%, AUC 0.74, P < 0.001) were associated with significant functional MR. The assessment of Ts-Dif showed an incremental value over the mitral valve tenting area for determining functional MR (χ(2) = 53.92 vs.49.11, P = 0.028). CONCLUSION: This cross-sectional study showed that LV global, but not regional systolic dyssynchrony, is a determinant of significant functional MR in patients with LV systolic dysfunction, and is incremental to the tenting area that is otherwise the strongest factor for mitral valve deformation.

LncRNA MFRL regulates the phenotypic switch of vascular smooth muscle cells to attenuate arterial remodeling by encoding a novel micropeptide MFRLP.

BACKGROUND: Arterial remodeling is a common pathophysiological change in the pathogenesis of cardiovascular diseases in which the phenotypic switch of vascular smooth muscle cells (VSMC) plays an important role. Recently, an increasing number of long non-coding RNAs(lncRNAs) have been shown to encode micropeptides that play biological roles and have great clinical transformation potential. However, the role of micropeptides encoded by lncRNAs in arterial remodeling has not been well studied and requires further exploration. METHODS AND RESULTS: Through bioinformatic analysis and experimental verification, we found that a new lncRNA, the mitochondrial function-related lncRNA (MFRL), encodes a 64-amino acid micropeptide, MFRLP. MFRL and MFRLP play important roles in the phenotypic switch of VSMC. Further experiments showed that MFRLP interacts with mitochondrial cytochrome b to reduce accumulation of reactive oxygen species, suppress mitophagy and inhibit the VSMC switch from contractile to synthetic phenotype. CONCLUSIONS: LncRNA MFRL encodes the micropeptide MFRLP, which interacts with mitochondrial cytochrome b to inhibit the VSMC switch from contractile to synthetic phenotype and improve arterial remodeling.

Genetic Association of Lipid-Lowering Drugs with Aortic Aneurysms: A Mendelian Randomization Study.

AIMS: The lack of effective pharmacotherapies for aortic aneurysms (AA) is a persistent clinical challenge. Lipid metabolism plays an essential role in AA. However, the impact of lipid-lowering drugs on AA remains controversial. The study aimed to investigate the genetic association between lipid-lowering drugs and AA. METHODS: Our research used publicly available data on genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) studies. Genetic instruments, specifically eQTLs related to drug-target genes and SNPs (single nucleotide polymorphisms) located near or within the drug-target loci associated with low-density lipoprotein cholesterol (LDL-C), have been served as proxies for lipid-lowering medications. Drug-Target Mendelian Randomization (MR) study is used to determine the causal association between lipid-lowering drugs and different types of AA. RESULTS: The MR analysis revealed that higher expression of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) was associated with increased risk of AA (OR = 1.58, 95% CI = 1.20-2.09, p = 1.20 × 10-03) and larger lumen size (aortic maximum area: OR = 1.28, 95% CI = 1.13-1.46, p = 1.48 × 10-04; aortic minimum area: OR = 1.26, 95% CI = 1.21-1.42, p = 1.78 × 10-04). PCSK9 (Proprotein convertase subtilisin/kexin type 9) and CETP (Cholesteryl ester transfer protein) show a suggestive relationship with AA (PCSK9: OR = 1.34, 95% CI = 1.10-1.63, p = 3.07 × 10-03; CETP: OR = 1.38, 95% CI = 1.06-1.80, p = 1.47 × 10-02). No evidence to support genetically mediated NPC1L1 (Niemann-Pick C1-Like 1) and LDLR (low-density lipoprotein cholesterol receptor) are associated with AA. CONCLUSIONS: This study provides causal evidence for the genetic association between lipid-lowering drugs and aortic aneurysms. Higher gene expression of HMGCR, PCSK9, and CETP increases AA risk. Furthermore, HMGCR inhibitors may link with smaller aortic lumen size.

This Mendelian Randomization study used publicly available data involving over 1 million individuals to demonstrate the causal relationship between five target genes of LDL-C-lowering medicines and the risk of aortic aneurysms, and implied one lipid-lowering drug may link with the lumen size of aortic aneurysms. Key findings High expression of HMGCR, PCSK9, and CETP was positively correlated with the risk of aortic aneurysms, highlighting that the corresponding lipid-lowering drugs may be preferred for preventing arterial aneurysms in high-risk individuals with dyslipidemia. We found that genetically predicted HMGCR inhibitors were positively associated with smaller aortic lumen size, which is the first time to support the causal association of gene HMGCR on the lumen size of aortic aneurysms.

Early LAAO device migration after combined atrial fibrillation ablation and left atrial appendage occlusion.

The combined procedure of catheter ablation and percutaneous left atrial appendage occlusion for patients with atrial fibrillation has been shown to be safe and feasible using radiofrequency energy or cryoballoon.

Baseline characteristics of patients with heart failure with mildly reduced or preserved ejection fraction: The FINEARTS-HF trial.

AIMS: To describe the baseline characteristics of participants in the FINEARTS-HF trial, contextualized with prior trials including patients with heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF). The FINEARTS-HF trial is comparing the effects of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo in reducing cardiovascular death and total worsening HF events in patients with HFmrEF/HFpEF. METHODS AND RESULTS: Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m2, elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials. CONCLUSIONS: FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population.

Fragmented Vortex in Heart Failure With Reduced Ejection Fraction: A Prospective Vector Flow Mapping Study.

OBJECTIVE: Heart failure with reduced ejection fraction (HFrEF) is associated with structural and functional left ventricular changes. We compared intracardiac vortices between patients with HFrEF and normal participants using echocardiographic vector flow mapping, a novel intracardiac vortex analysis technology. METHODS: Transthoracic echocardiography was performed on 20 patients with HFrEF (age: 61 ± 15 y, 15 men) and 20 normal participants (age: 59 ± 12 y, 12 men) age- and sex-balanced at the cohort level. Systolic and diastolic energy loss, area (indexed by left ventricular end-diastolic diameter), circulation (reflects vortex strength) and relative positions of the largest vortex during systole (S-vortex), early (E-vortex) and late (A-vortex) diastole and maximal number of vortices in a single frame (MNV) were assessed. DISCUSSION: Patients with HFrEF had disproportionately sized vortices with smaller indexed vortex areas (p < 0.0001), and more fragmented vortices with higher MNV during both systole (p = 0.030) and diastole (p < 0.0001). These accompanied higher diastolic energy loss (p = 0.001). Additionally, the E-vortex (p = 0.002) and A-vortex (p < 0.0001) were more apically positioned, and the S-vortex was weaker (p = 0.033) in patients with HFrEF. More severe fragmentation (higher MNV) correlated with worse energy efficiency (higher energy loss). CONCLUSION: Patients with HFrEF had more fragmented intracardiac vortices and lower energy efficiency predominantly during diastole.

Complete region of interest reconstruction by fusing multiview deformable three-dimensional transesophageal echocardiography images.

BACKGROUND: While three-dimensional transesophageal echocardiography (3D TEE) has been increasingly used for assessing cardiac anatomy and function, it still suffers from a limited field of view (FoV) of the ultrasound transducer. Therefore, it is difficult to examine a complete region of interest without moving the transducer. Existing methods extend the FoV of 3D TEE images by mosaicing multiview static images, which requires synchronization between 3D TEE images and electrocardiogram (ECG) signal to avoid deformations in the images and can only get the widened image at a specific phase. PURPOSE: This work aims to develop a novel multiview nonrigid registration and fusion method to extend the FoV of 3D TEE images at different cardiac phases, avoiding the bias toward the specifically chosen phase. METHODS: A multiview nonrigid registration and fusion method is proposed to enlarge the FoV of 3D TEE images by fusing dynamic images captured from different viewpoints sequentially. The deformation field for registering images is defined by a collection of affine transformations organized in a graph structure and is estimated by a direct (intensity-based) method. The accuracy of the proposed method is evaluated by comparing it with two B-spline-based methods, two Demons-based methods, and one learning-based method VoxelMorph. Twenty-nine sequences of in vivo 3D TEE images captured from four patients are used for the comparative experiments. Four performance metrics including checkerboard volumes, signed distance, mean absolute distance (MAD), and Dice similarity coefficient (DSC) are used jointly to evaluate the accuracy of the results. Additionally, paired t-tests are performed to examine the significance of the results. RESULTS: The qualitative results show that the proposed method can align images more accurately and obtain the fused images with higher quality than the other five methods. Additionally, in the evaluation of the segmented left atrium (LA) walls for the pairwise registration and sequential fusion experiments, the proposed method achieves the MAD of (0.07 ± 0.03) mm for pairwise registration and (0.19 ± 0.02) mm for sequential fusion. Paired t-tests indicate that the results obtained from the proposed method are more accurate than those obtained by the state-of-the-art VoxelMorph and the diffeomorphic Demons methods at the significance level of 0.05. In the evaluation of left ventricle (LV) segmentations for the sequential fusion experiments, the proposed method achieves a DSC of (0.88 ± 0.08), which is also significantly better than diffeomorphic Demons at the 0.05 level. The FoVs of the final fused 3D TEE images obtained by our method are enlarged around two times compared with the original images. CONCLUSIONS: Without selecting the static (ECG-gated) images from the same cardiac phase, this work addressed the problem of limited FoV of 3D TEE images in the deformable scenario, obtaining the fused images with high accuracy and good quality. The proposed method could provide an alternative to the conventional fusion methods that are biased toward the specifically chosen phase.

30-Day Outcomes of Transcatheter Tricuspid Annuloplasty With the K-Clip System: A Single-Center, Observational Study.

Background: Surgery for isolated functional tricuspid regurgitation (TR) poses a high risk. Several transcatheter approaches are being evaluated for the treatment of such patients. The K-Clip system is a percutaneous approach designed for functional TR; however, its utility remains unknown. Objectives: This study aimed to report the 30-day echocardiographic and clinical outcomes with the K-Clip system for severe TR, including changes in TR severity and NYHA functional class. Methods: Transcatheter tricuspid valve annuloplasty was performed in 39 patients with intermediate or high surgical risk who underwent the K-Clip system. The right internal jugular vein procedure was performed with annuloplasty guided by fluoroscopy and echocardiography. The primary outcomes were clinical success and all-cause mortality at the 30-day follow-up. Results: The K-Clip was successfully implanted in all cases, with 1 to 3 devices deployed. At the 30-day follow-up, none of the patients had died. TR severity was reduced by at least one grade in all patients. There were no severe procedural or 30-day adverse events, except for 1 new pacemaker implantation. The proportion of NYHA class III-IV patients decreased from 79.5% to 5.1%, and the ascites disappeared. The 6-minute walk distance increased by 78 m (P < 0.05), and the Kansas City Cardiomyopathy Questionnaire score improved by 11 points (P < 0.05). Conclusions: The K-Clip device is practical, safe, and effective for patients with severe TR. A 30-day reduction in TR and enhanced cardiac function and quality of life were associated with transcatheter tricuspid annuloplasty using the K-Clip device, according to short-term follow-up studies. (Confirmatory Clinical Study of Treating Tricuspid Regurgitation With K-Clip TM Transcatheter Annuloplasty System [TriStar]; NCT05173233).

First-in-human study of the K-Clip™ transcatheter annular repair system for severe functional tricuspid regurgitation.

BACKGROUND: Severe TR is associated with impaired prognosis while limited interventional options available. The purpose of this observational first-in-human experience with the K-Clip™ transcatheter tricuspid annular reconstruction system is to investigate its feasibility, safety as well as short-term clinical impact on patients with severe functional tricuspid regurgitation (TR). METHODS: In this compassionate-use, prospective, multi-center, single-arm study, 15 patients with severe symptomatic functional TR were treated with the K-Clip™ system and followed up at 30 days after discharge. Feasibility endpoints consisted of safety (major clinical cardiovascular events (MACEs), echocardiographic, clinical and functional endpoints. RESULTS: All the 15 patients (9 males, 72.67 ± 9.42 years of age) successfully received implants and no MACEs were reported throughout the study at 30 days. Between baseline and 30 days, echocardiography showed remarkable reduction of tricuspid annular circumference and area by 14.30% and 25.96%. Improvement of ≥ + 2 grade and ≥ +3 grade TR was presented in 9/15(60.00%) and 4/15(26.67%) respectively while 10/15(66.67%) of patients had ≤ moderate TR. Clinical evaluation indicated that 86.67% of patients were finally in NYHA functional class I or II (p<0.001) and overall Kansas City Cardiomyopathy Questionnaire score improved from 62.28 ± 18.97 to 77.90 ± 11.70 (p = 0.016). CONCLUSION: Our first-in-human results of the transcatheter tricuspid annular reconstruction using the K-Clip™ system demonstrated initial favorable procedural success, acceptable safety and remarkable TR reduction in consistent with significant clinical improvement. Larger-scaled prospective trials with longer follow-up duration are warranted to further determine whether these promising findings could be promoted to a broader population in the long term.

Echocardiographic Imaging in Transcatheter Structural Intervention: An AAE Review Paper.

Transcatheter structural heart intervention (TSHI) has gained popularity over the past decade as a means of cardiac intervention in patients with prohibitive surgical risks. Following the exponential rise in cases and devices developed over the period, there has been increased focus on developing the role of "structural imagers" amongst cardiologists. This review, as part of a growing initiative to develop the field of interventional echocardiography, aims to highlight the role of echocardiography in myriad TSHIs available within Asia. We first discuss the various echocardiography-based imaging modalities, including 3-dimensional echocardiography, fusion imaging, and intracardiac echocardiography. We then highlight a selected list of structural interventions available in the region-a combination of established interventions alongside novel approaches-describing key anatomic and pathologic characteristics related to the relevant structural heart diseases, before delving into various aspects of echocardiography imaging for each TSHI.