CIB2 Is a Novel Endogenous Repressor of Atrial Remodeling.

BACKGROUND: Atrial fibrillation (AF) is a highly prevalent condition that can cause or exacerbate heart failure, is an important risk factor for stroke, and is associated with pronounced morbidity and death. Genes uniquely expressed in the atria are known to be essential for maintaining atrial structure and function. Atrial tissue remodeling contributes to arrhythmia recurrence and maintenance. However, the mechanism underlying atrial remodeling remains poorly understood. This study was designed to investigate whether other uncharacterized atrial specific genes play important roles in atrial physiology and arrhythmogenesis. METHODS: RNA-sequencing analysis was used to identify atrial myocyte specific and angiotensin II-responsive genes. Genetically modified, cardiomyocyte-specific mouse models (knockout and overexpression) were generated. In vivo and in vitro electrophysiological, histology, and biochemical analyses were performed to determine the consequences of CIB2 (calcium and integrin binding family member 2 protein) gain and loss of function in the atrium. RESULTS: Using RNA-sequencing analysis, we identified CIB2 as an atrial-enriched protein that is significantly downregulated in the left atria of patients with AF and mouse models of AF from angiotensin II infusion or pressure overload. Using cardiomyocyte-specific Cib2 knockout (Cib2-/-) and atrial myocyte-specific Cib2-overexpressing mouse models, we found that loss of Cib2 enhances AF occurrence, prolongs AF duration, and correlates with a significant increase in atrial fibrosis under stress. Conversely, Cib2 overexpression mitigates AF occurrence and atrial fibrosis triggered by angiotensin II stress. Mechanistically, we revealed that CIB2 competes with and inhibits CIB1-mediated calcineurin activation, thereby negating stress-induced structural remodeling and AF. CONCLUSIONS: Our data suggest that CIB2 represents a novel endogenous and atrial-enriched regulator that protects against atrial remodeling and AF under stress conditions. Therefore, CIB2 may represent a new potential target for treating AF.

Association between left atrial myopathy and sarcomere mutation in patients with hypertrophic cardiomyopathy: insights into left atrial strain by MRI feature tracking.

OBJECTIVES: Left atrial (LA) myopathy, characterized by LA enlargement and mechanical dysfunction, is associated with worse prognosis in hypertrophic cardiomyopathy (HCM) while the impact of sarcomere mutation on LA myopathy remains unclear. We aimed to assess the association between LA myopathy and sarcomere mutation and to explore the incremental utility of LA strain in mutation prediction. METHODS: A total of 105 consecutive HCM patients (mean age 47.8 ± 11.9 years, 71% male) who underwent HCM-related gene screening and cardiac MRI were retrospectively enrolled. LA volume, ejection fraction and strain indices in reservoir, conduit, and booster-pump phases were investigated respectively. RESULTS: Fifty mutation-positive patients showed higher LA maximal volume index (59.4 ± 28.2 vs 43.8 ± 18.1 mL/m2, p = 0.001), lower reservoir (21.3 ± 7.9 vs 26.2 ± 6.6%, p < 0.001), and booster-pump strain (12.1 ± 5.4 vs 17.1 ± 5.0%, p < 0.001) but similar conduit strain (9.2 ± 4.5 vs 9.1 ± 4.5%, p = 0.909) compared with mutation-negative patients. In multivariate logistic regression, LA booster-pump strain was associated with sarcomere mutation (odds ratio = 0.86, 95% confidence interval: 0.77-0.96, p = 0.010) independent of maximal wall thickness, late gadolinium enhancement, and LA volume. Furthermore, LA booster-pump strain showed incremental value for mutation prediction added to Mayo II score (AUC 0.798 vs 0.709, p = 0.024). CONCLUSIONS: In HCM, mutation-positive patients suffered worse LA enlargement and worse reservoir and booster-pump functions. LA booster-pump strain was a strong factor for sarcomere mutation prediction added to Mayo II score. CLINICAL RELEVANCE STATEMENT: The independent association between sarcomere mutation and left atrial mechanical dysfunction provide new insights into the pathogenesis of atrial myopathy and is helpful to understand the adverse prognosis regarding atrial fibrillation and stroke in mutation-positive patients. KEY POINTS: • In patients with hypertrophic cardiomyopathy, left atrial (LA) reservoir and booster-pump function, but not conduit function, were significantly impaired in mutation-positive patients compared with mutation-negative patients. • LA booster-pump strain measured by MRI-derived feature tracking is feasible to predict sarcomere mutation with high incremental value added to Mayo II score.

Assessment of late gadolinium enhancement in hypertrophic cardiomyopathy improves risk stratification based on current guidelines.

BACKGROUND AND AIMS: Identifying patients with hypertrophic cardiomyopathy (HCM) who are candidates for implantable cardioverter defibrillator (ICD) implantation in primary prevention for sudden cardiac death (SCD) is crucial. The aim of this study was to externally validate the 2022 European Society of Cardiology (ESC) model and other guideline-based ICD class of recommendation (ICD-COR) models and explore the utility of late gadolinium enhancement (LGE) in further risk stratification. METHODS: Seven hundred and seventy-four consecutive patients who underwent cardiac magnetic resonance imaging were retrospectively enrolled. RESULTS: Forty-six (5.9%) patients reached the SCD-related endpoint during 7.4 ± 2.5 years of follow-up. Patients suffering from SCD had higher ESC Risk-SCD score (4.3 ± 2.4% vs. 2.8 ± 2.1%, P < .001) and LGE extent (13.7 ± 9.4% vs. 4.9 ± 6.6%, P < .001). Compared with the 2014 ESC model, the 2022 ESC model showed increased area under the curve (.76 vs. .63), sensitivity (76.1% vs. 43.5%), positive predictive value (16.8% vs. 13.6%), and negative predictive value (98.1% vs. 95.9%). The C-statistics for SCD prediction of 2011 American College of Cardiology (ACC)/American Heart Association (AHA), 2014 ESC, 2020 AHA/ACC, and 2022 ESC models were .68, .64, .76 and .78, respectively. Furthermore, in patients without extensive LGE, LGE ≥5% was responsible for seven-fold SCD risk after multivariable adjustment. Whether in ICD-COR II or ICD-COR III, patients with LGE ≥5% and <15% showed significantly worse prognosis than those with LGE <5% (all P < .001). CONCLUSIONS: The 2022 ESC model performed better than the 2014 ESC model with especially improved sensitivity. LGE enabled further risk stratification based on current guidelines.

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction.

An efficient protocol for the synthesis of polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine-3,4b,5,6,7(1H)-pentacarboxylates was developed by a three-component reaction. In the absence of any catalyst, the three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates and 5,6-unsubstituted 1,4-dihydropyridines in refluxing acetonitrile afforded polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine-3,4b,5,6,7(1H)-pentacarboxylates in high yields and with high diastereoselectivity. The reaction was finished by in situ generation of activated 5-(alkylimino)cyclopenta-1,3-dienes from addition of alkyl isocyanide to two molecules of but-2-ynedioates and sequential formal [3 + 2] cycloaddition reaction with 5,6-unsubstituted 1,4-dihydropyridine.

Radiomics features of pericoronary adipose tissue improve CT-FFR performance in predicting hemodynamically significant coronary artery stenosis.

OBJECTIVES: To evaluate the value of radiomics-based model of pericoronary adipose tissue (PCAT) combined with CT fractional flow reserve (CT-FFR) in predicting hemodynamically significant coronary stenosis. METHODS: Patients with suspected or known coronary artery disease, who had coronary computed tomography angiography (CCTA), invasive coronary angiography (ICA), and FFR within 1 month, were retrospectively included. Radiomics features of lesion-based PCAT were extracted. The lesion-specific CT-FFR values, CCTA-derived diameter stenosis, lesion length, and PCAT attenuation were also measured. FFR values were used as the reference standard to assess the diagnostic performance of radiomics model, CT-FFR, and combined model for detection of flow-limiting stenosis. RESULTS: A total of 146 patients with 180 lesions were included in the study. All lesions were divided into training and validation cohorts at a ratio of 2:1. CT-FFR model exhibited the highest area under the curve (AUC) (0.803 for training, 0.791 for validation) in predicting hemodynamically significant stenosis, followed by radiomics model (0.776 for training, 0.744 for validation). However, no statistically significant difference was found between the AUCs of the above two models (p > 0.05). When CT-FFR was combined with radiomics model, the AUC reached 0.900 for training cohort and 0.875 for validation cohort, which were significantly higher than that of CT-FFR and radiomics model alone (both p < 0.05). CONCLUSION: The diagnostic performance of PCAT radiomics model was comparable to that of CT-FFR for identification of ischemic coronary stenosis. Adding PCAT radiomics model to CT-FFR showed incremental value in discriminating flow-limiting from non-flow-limiting lesions. KEY POINTS: • Radiomics analysis of lesion-based PCAT is potentially an alternative method to identify hemodynamic significance of coronary artery stenosis. • Adding radiomics model of PCAT to CT-FFR improved diagnostic performance for the detection of flow-limiting coronary stenosis. • Radiomics features + CT-FFR is a promising noninvasive method for comprehensive evaluation of hemodynamic significance of coronary artery stenosis.

Cardiac remodeling after tricuspid valve repair in Ebstein's anomaly: a magnetic resonance study.

OBJECTIVES: We aimed to evaluate immediate and midterm cardiac remodeling after surgery by cardiac magnetic resonance (CMR) in Ebstein's anomaly (EA), and also to investigate preoperative predictors of right ventricular (RV) normalization. METHODS: We retrospectively analyzed CMR parameters of the whole heart in adult patients with EA before surgery, at discharge and follow-up. RESULTS: A total of 26 patients were included and performed CMR at 7 days (interquartile range, 3-13 days) before surgery. Immediate postoperative CMR was finished at discharge (median: 8 [7-9] days; n = 18) and follow-up CMR at 187 days (interquartile range, 167-356 days; n = 17). RV and right atrial (RA) volumes promptly decreased immediately after surgery and at follow-up (all p < 0.05). RV ejection fraction decreased significantly at discharge (p < 0.05) but recovered at follow-up (p = 0.18). However, RV global longitudinal strain and RA reservoir strain were significantly impaired immediately and midterm after surgery (all p < 0.05). Indexed left ventricular (LV) end-diastolic volume, stroke volume, as well as global longitudinal strain increased from preoperative to follow-up (all p < 0.05). Patients who achieved normalization of RV volumes after surgery had smaller severity index and RV and RA volumes and higher LV ejection fraction and RA reservoir strain at baseline than patients without RV normalization (all p < 0.05). CONCLUSIONS: Reverse biventricular remodeling took place in EA after tricuspid valve surgery. Tricuspid valve reconstruction should be performed before deterioration of RV volume overload and LV function to achieve reverse RV remodeling. Key Points • After removing the volume load of tricuspid regurgitation in Ebstein's anomaly, reverse remodeling was detected by CMR in both left and right heart at midterm follow-up. • Tricuspid valve reconstruction should be performed before deterioration of RV volume overload and LV function to achieve reverse RV remodeling.

Reverse remodeling of left atrium assessed by cardiovascular magnetic resonance feature tracking in hypertrophic obstructive cardiomyopathy after septal myectomy.

BACKGROUND: Assessing the structure and function of left atrium (LA) is crucial in hypertrophic obstructive cardiomyopathy (HOCM) because LA remodeling correlates with atrial fibrillation. However, few studies have investigated the potential effect of myomectomy on LA phasic remodeling in HOCM after myectomy using cardiovascular magnetic resonance (CMR) feature tracking (FT). This study aims to evaluate the LA structural and functional remodeling with HOCM after myectomy by CMR-FT and to further investigate the determinants of LA reverse remodeling. METHODS: In this single-center study, we retrospectively studied 88 patients with HOCM who received CMR before and after myectomy between January 2011 and June 2021. Preoperative and postoperative LA parameters derived from CMR-FT were compared, including LA reservoir function (total ejection fraction [EF], total strain [εs], peak positive strain rate [SRs]), conduit function (passive EF, passive strain [εe], peak early negative strain rate [SRe]) and booster function (booster EF, active strain [εa], late peak negative strain rate [SRa]). Eighty-six healthy participants were collected for comparison. Univariate and multivariate linear regression identified variables associated with the rate of change of εa. RESULTS: Compared with preoperative parameters, LA reservoir function (total EF, εs, SRs), booster function (booster EF, εa, SRa), and SRe were significantly improved after myectomy (all P < 0.05), while no significant differences were observed in passive EF and εe. Postoperative patients with HOCM still had larger LA and worse LA function than healthy controls (all P < 0.05). After analyzing the rates of change in LA parameters, LA boost function, especially εa, showed the most dramatic improvement beyond the improvements in reservoir function, conduit function, and volume. In multivariable regression analysis, minimum LA volume index (adjusted ß = - 0.39, P < 0.001) and Δleft ventricular outflow tract (LVOT) pressure gradient (adjusted ß = - 0.29, P = 0.003) were significantly related to the rate of change of εa. CONCLUSIONS: Patients with HOCM after septal myectomy showed LA reverse remodeling with a reduction in LA size and restoration in LA reservoir and booster function but unchanged LA conduit function. Among volumetric and functional changes, booster function had the greatest improvement postoperatively. Besides, preoperative LAVmin index and ΔLVOT might be potential factors associated with the degree of improvement in εa.

Incremental prognostic value of left atrial and biventricular feature tracking in dilated cardiomyopathy: a long-term study.

BACKGROUND: Despite the use of cardiovascular magnetic resonance (CMR) feature tracking (FT) imaging to detect myocardial deformation, the optimal strain index in dilated cardiomyopathy (DCM) is unclear. This study aimed to determine whether atrial and biventricular strains can provide the greatest or joint incremental prognostic value in patients with DCM over a long follow-up period. METHODS: Four hundred-twelve DCM patients were included retrospectively. Comprehensive clinical evaluation and imaging investigations were obtained, including measurements of CMR-FT derived left atrial (LA) reservoir, conduit, booster strain (εs, εe, εa); left ventricular (LV) and right ventricular (RV) global longitudinal, radial, circumferential strain (GLS, GRS, GCS). All patients were followed up for major adverse cardiac events (MACE) including all-cause mortality, heart transplantation, and implantable cardioverter defibrillator discharge. The predictors of MACE were examined with univariable and multivariable Cox regression analysis. Subsequently, nested Cox regression models were built to evaluate the incremental prognostic value of strain parameters. The incremental predictive power of strain parameters was assessed by Omnibus tests, and the model performance and discrimination were evaluated by Harrell C-index and integrated discrimination improvement (IDI) analysis. Patient survival was illustrated by Kaplan-Meier curves and differences were evaluated by log-rank test. RESULTS: During a median follow-up of 5.0 years, MACE were identified in 149 (36%) patients. LAεe, LVGLS, and RVGLS were the most predictive strain parameters for MACE (AUC: 0.854, 0.733, 0.733, respectively). Cox regression models showed that the predictive value of LAεe was independent from and incremental to LVGLS, RVGLS, and baseline variables (HR 0.74, 95% CI 0.68-0.81, P < 0.001). In reclassification analysis, the addition of LAεe provided the best discrimination of the model (χ2 223.34, P < 0.001; C-index 0.833; IDI 0.090, P < 0.001) compared with LVGLS and RVGLS models. Moreover, LAεe with a cutoff of 5.3% further discriminated the survival probability in subgroups of patients with positive LGE or reduced LVEF (all log-rank P < 0.001). CONCLUSION: LAεe provided the best prognostic value over biventricular strains and added incremental value to conventional clinical predictors for patients with DCM.

Effect of a video-based exercise intervention on depression and sleep conditions of peritoneal dialysis patients.

OBJECTIVE: To evaluate the effectiveness of a video-based exercise intervention on depression and sleep conditions of peritoneal dialysis (PD) patients. MATERIALS AND METHODS: Participants satisfying the inclusion and exclusion criteria were recruited from the Peritoneal Dialysis Center, Department of Nephrology of the First Affiliated Hospital of Guangxi Medical University, and they were divided into an intervention group and a control group. The intervention group received video-based exercise intervention while the control group received routine care. Then their BDI-II and PSQI scores were collected and analyzed before and after the intervention. RESULTS: There were no significant differences in BDI-II score and the seven components of PSQI score between the two groups at the baseline measures (p > 0.05). However, after 12 weeks of intervention, the intervention group had a significantly lower score in BDI-II (p < 0.05) and in six components of PSQI (p < 0.05), with the exception of the "use of sleep medications" subscale (p > 0.05). Their depression level also improved significantly after intervention (p < 0.05), while that of the control group did not change significantly(p > 0.05). CONCLUSION: The video-based exercise intervention is safe and can remarkably improve the depression and sleep conditions of PD patients and is thus worthwhile to be applied widely.

Effectiveness of a video-based exercise program on nutritional status and quality of life of peritoneal dialysis patients: A pilot randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a video-based exercise program on nutritional status and quality of life (QOL) of peritoneal dialysis (PD) patients. MATERIALS AND METHODS: Participants satisfying the inclusion and exclusion criteria were recruited and divided into the intervention group and the control group. The intervention group received video-based exercise based on a manual advocated by the National Kidney Foundation, while the control group received routine exercise guidance. Their nutritional indicators and the Quality of Life Scale for Peritoneal Dialysis patients (QLSPD) scores were collected and analyzed. RESULTS: No adverse events occurred during the study. Baseline data between the two groups were comparable, and there were no significant differences in body mass index (BMI) (t = 0.214, p = 0.831), triceps skin fold thickness (TSF) (t = 0.407, p = 0.685), arm muscle circumference (AMC) (t = 0.310, p = 0.757), grip strength (Gs) (t = 0.557, p = 0.579), calf circumference (Cc) (t = 0.441, p = 0.660), serum albumin (Alb) (t = 0.261, p = 0.795), prealbumin (PA) (t = 0.218, p = 0.828), hemoglobin (Hb) (t = 0.114, p = 0.909), triglyceride (TG) (t = 0.192, p = 0.848), total cholesterol (TC) (t = 0.092, p = 0.927), low-density lipoprotein (LDL) (t = 0.124, p = 0.902), high-density lipoprotein (HDL) (t = 0.265, p = 0.792), blood urea nitrogen (BUN) (t = 0.540, p = 0.590), serum creatinine (SCr) (t = 0.255, p = 0.799), total urea clearance index (Kt/V) (t = 0.958, p = 0.340), total creatinine clearance rate (Ccr) (t = 0.166, p = 0.868), protein equivalent of nitrogen appearance (nPNA) (t = 0.240, p = 0.811), and QLSPD scores (p > 0.05) between the two groups at the baseline measures. However, after 12 weeks of intervention, the AMC (t = 2.993, p = 0.003) and Cc (t = 2.811, p = 0.006) of the intervention group improved significantly compared with the control group. The BMI (t = 2.068, p = 0.041) and TSF (t = 2.578, p = 0.011) showed a trend of improvement compared with baseline. And the intervention group scored less in body physiology function (t = 7.084, p < 0.001), disease factors (t = 13.336, p < 0.001), mental state (t = 9.555, p < 0.001), and social role (t = 5.156, p < 0.001) components, while their satisfaction hardly changed (t = 0.240, p = 0.811). CONCLUSION: The video-based exercise intervention is safe and can remarkably improve the nutritional status and QOL of PD patients.

A Micro-Topography Measurement and Compensation Method for the Key Component Surface Based on White-Light Interferometry.

The grinding grooves of material removal machining and the residues of a machining tool on the key component surface cause surface stress concentration. Thus, it is critical to carry out precise measurements on the key component surface to evaluate the stress concentration. Based on white-light interferometry (WLI), we studied the measurement distortion caused by the reflected light from the steep side of the grinding groove being unable to return to the optical system for imaging. A threshold value was set to eliminate the distorted measurement points, and the cubic spline algorithm was used to interpolate the eliminated points for compensation. The compensation result agrees well with the atomic force microscope (AFM) measurement result. However, for residues on the surface, a practical method was established to obtain a microscopic 3D micro-topography point cloud and a super-depth-of-field fusion image simultaneously. Afterward, the semantic segmentation network U-net was adopted to identify the residues in the super-depth-of-field fusion image and achieved a recognition accuracy of 91.06% for residual identification. Residual feature information, including height, position, and size, was obtained by integrating the information from point clouds and super-depth-of-field fusion images. This work can provide foundational data to study surface stress concentration.

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition.

The three-component reaction of isoquinolines, dialkyl acetylenedicarboxylates, and 5,6-unsubstituted 1,4-dihydropyridines in acetonitrile at room temperature afforded functionalized isoquinolino[1,2-f][1,6]naphthyridines in good yields and with high diastereoselectivity. More importantly, the formal [2 + 2] cycloaddition reaction of dialkyl acetylenedicarboxylates and 5,6-unsubstituted 1,4-dihydropyridines in refluxing acetonitrile gave unique 2-azabicyclo[4.2.0]octa-3,7-dienes as major products and 1,3a,4,6a-tetrahydrocyclopenta[b]pyrroles as minor products via further rearrangement.

Construction of a Recyclable DNAzyme Motor for MUC1-Specific Glycoform In Situ Quantification.

Changes in the glycosylation content, especially in specific proteins, are of great importance for interpreting the mechanisms and development of certain diseases. However, current detection techniques are limited by the weak ionization efficiency of glycosyls and poor anti-interference of fluorescence signals. Herein, we present a general in situ quantification strategy for protein-specific glycoforms by constructing a recyclable DNAzyme motor for mass spectrometric detection using MUC1-specific sialic acid (Sia) as a model. This approach relies on a DNAzyme-based recycling strategy and two well-designed probes: a protein and a glycan probe. The protein probe consists of an aptamer and a DNAzyme. The glycan probe contains three functional domains: a DNAzyme complementary sequence, a substrate peptide segment, and a dibenzocyclooctyne tag. First, these two probes bind to their corresponding targets and trigger hybridization between adjacent probes on the same protein. With the help of the metal cofactor, the DNAzyme of the protein probe hydrolyzes the double-stranded glycan probe. The protein probe then reverts to a single-stranded state and remains intact for the next round of hybridization and cleavage. In this way, the recyclable DNAzyme motor can hydrolyze all glycan probes bound to the target protein. Finally, the reporter peptide released from the hydrolyzed glycan probes can be quantified by mass spectrometry, thereby converting the signal of the protein-specific glycoform to that of mass spectrometry. This strategy has been successfully used for in situ quantification of MUC1-specific Sia in different breast cancer cell lines. It provides a promising platform for protein-specific glycoform quantification.

Correlation between left ventricular fractal dimension and impaired strain assessed by cardiac MRI feature tracking in patients with left ventricular noncompaction and normal left ventricular ejection fraction.

OBJECTIVES: To investigate the correlation between the extent of excessive trabeculation assessed by fractal dimension (FD) and myocardial contractility assessed by cardiac MRI feature tracking in patients with left ventricular noncompaction (LVNC) and normal left ventricular ejection fraction (LVEF). METHODS: Forty-one LVNC patients with normal LVEF (≥ 50%) and 41 healthy controls were retrospectively included. All patients fulfilled three available diagnostic criteria on MRI. Cardiac MRI feature tracking was performed on cine images to determine left ventricular (LV) peak strains in three directions: global radial strain (GRS), global circumferential strain (GCS), and global longitudinal strain (GLS). The complexity of excessive trabeculation was quantified by fractal analysis on short-axis cine stacks. RESULTS: Compared with controls, patients with LVNC had impaired GRS, GCS, and GLS (all p < 0.05). The global, maximal, and regional FD values of the LVNC population were all significantly higher than those of the controls (all p < 0.05). Global FD was positively correlated with the end-diastolic volume index, end-systolic volume index, and stroke volume index (r = 0.483, 0.505, and 0.335, respectively, all p < 0.05), but negatively correlated with GRS and GCS (r = - 0.458 and 0.508, respectively, both p < 0.001). Moreover, apical FD was also weakly associated with LVEF and GLS (r = - 0.249 and 0.252, respectively, both p < 0.05). CONCLUSION: In patients with LVNC, LV systolic dysfunction was detected early by cardiac MRI feature tracking despite the presence of normal LVEF and was associated with excessive trabecular complexity assessed by FD. KEY POINTS: • Left ventricular global strain was already impaired in patients with extremely prominent excessive trabeculation but normal left ventricular ejection fraction. • An increased fractal dimension was associated with impaired deformation in left ventricular noncompaction.

Integrin ß1D Deficiency-Mediated RyR2 Dysfunction Contributes to Catecholamine-Sensitive Ventricular Tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary heart disease characterized by fatty infiltration, life-threatening arrhythmias, and increased risk of sudden cardiac death. The guideline for management of ARVC in patients is to improve quality of life by reducing arrhythmic symptoms and to prevent sudden cardiac death. However, the mechanism underlying ARVC-associated cardiac arrhythmias remains poorly understood. METHODS: Using protein mass spectrometry analyses, we identified that integrin ß1 is downregulated in ARVC hearts without changes to Ca2+-handling proteins. As adult cardiomyocytes express only the ß1D isoform, we generated a cardiac specific ß1D knockout mouse model and performed functional imaging and biochemical analyses to determine the consequences of integrin ß1D loss on function in the heart in vivo and in vitro. RESULTS: Integrin ß1D deficiency and RyR2 Ser-2030 hyperphosphorylation were detected by Western blotting in left ventricular tissues from patients with ARVC but not in patients with ischemic or hypertrophic cardiomyopathy. Using lipid bilayer patch clamp single channel recordings, we found that purified integrin ß1D protein could stabilize RyR2 function by decreasing RyR2 open probability, mean open time, and increasing mean close time. Also, ß1D knockout mice exhibited normal cardiac function and morphology but presented with catecholamine-sensitive polymorphic ventricular tachycardia, consistent with increased RyR2 Ser-2030 phosphorylation and aberrant Ca2+ handling in ß1D knockout cardiomyocytes. Mechanistically, we revealed that loss of DSP (desmoplakin) induces integrin ß1D deficiency in ARVC mediated through an ERK1/2 (extracellular signal-regulated kinase 1 and 2)-fibronectin-ubiquitin/lysosome pathway. CONCLUSIONS: Our data suggest that integrin ß1D deficiency represents a novel mechanism underlying the increased risk of ventricular arrhythmias in patients with ARVC.

General In Situ Photoactivation Route with IPCE over 80% toward CdS Photoanodes for Photoelectrochemical Applications.

Cost-effective photoanodes with remarkable electronic properties are highly demanded for practical photoelectrochemical (PEC) water splitting. The ability to manipulate the surface carrier separation and recombination is pivotal for achieving high PEC performance for water splitting. Here, a facile and economical approach is reported for substantially improving the surface charge separation property of CdS photoanodes through in situ photoactivation, which significantly reduces surface charge recombination through the formation of thiosulfate ion which is favorable to the transfer of photogenerated holes and a uniform nanoporous morphology via the dissolving Cd2+ with phosphate ions on the surface of CdS. The resulting CdS electrodes through scalable particle transfer method exhibit nearly tripled photocurrents, with an incident-photon-to-current conversion efficiency (IPCE) at 480 nm exceeding 80% at 0.6 V versus reversible hydrogen electrode (RHE). And the CdS thin films prepared from chemical bath deposition display quadrupled photocurrents after the stir and PEC activation, with an IPCE of 91.7% at 455 nm and 0.6 V versus RHE. With the suppression of photocorrosion in alkaline borate buffer, the activated photoanodes show great stability for solar hydrogen production at the sacrifice of sulfite. This work brings insights into the design of nanoporous metal sulfide semiconductors for solar water splitting.

Prognostic significance of myocardial fibrosis and CMR characteristics in bicuspid aortic valve with moderate and severe aortic insufficiency.

OBJECTIVES: This study attempted to evaluate the characteristics and prognostic value of myocardial fibrosis (MF) in aortic insufficiency (AI) patients with bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) by cardiac magnetic resonance (CMR). METHODS: A total of 314 adults with CMR-diagnosed AI were retrospectively retrieved. Of them, 166 patients with moderate or severe AI were included and divided into two groups: BAV group (N = 46) and a TAV group (N = 120). The presence and characteristics of MF were assessed with CMR. The patients were followed for adverse clinical events. The prognostic capability of the parameters was assessed using Cox regression model. RESULTS: LV fibrosis was more common in the BAV group than in the TAV group (65.2% vs. 45.0%; p = 0.020). There was a strong association between BAV and MF even after adjusting for clinical and imaging variables (odds ratio: 3.57; p = 0.031). Kaplan-Meier analysis showed a higher rate of clinical adverse events in AI+BAV patients with MF during a median follow-up of 4.7 years. Multivariate Cox regression analysis showed that late gadolinium enhancement (LGE) was an independent predictor of clinical adverse outcome. CONCLUSION: MF is more common in AI with BAV than with TAV and is a predictor of clinical adverse events. KEY POINTS: • The presence and extent of late gadolinium enhancement of left ventricular were more common and severer in the bicuspid aortic valve group than in the tricuspid aortic valve group in aortic insufficiency patients. • Bicuspid aortic valve was an independent factor for myocardial fibrosis in aortic insufficiency patients. • Late gadolinium enhancement could be used as an independent predictor of adverse clinical events in this population.

Deep learning algorithm to improve hypertrophic cardiomyopathy mutation prediction using cardiac cine images.

OBJECTIVES: The high variability of hypertrophic cardiomyopathy (HCM) genetic phenotypes has prompted the establishment of risk-stratification systems that predict the risk of a positive genetic mutation based on clinical and echocardiographic profiles. This study aims to improve mutation-risk prediction by extracting cardiovascular magnetic resonance (CMR) morphological features using a deep learning algorithm. METHODS: We recruited 198 HCM patients (48% men, aged 47 ± 13 years) and divided them into training (147 cases) and test (51 cases) sets based on different genetic testing institutions and CMR scan dates (2012, 2013, respectively). All patients underwent CMR examinations, HCM genetic testing, and an assessment of established genotype scores (Mayo Clinic score I, Mayo Clinic score II, and Toronto score). A deep learning (DL) model was developed to classify the HCM genotypes, based on a nonenhanced four-chamber view of cine images. RESULTS: The areas under the curve (AUCs) for the test set were Mayo Clinic score I (AUC: 0.64, sensitivity: 64.29%, specificity: 47.83%), Mayo Clinic score II (AUC: 0.70, sensitivity: 64.29%, specificity: 65.22%), Toronto score (AUC: 0.74, sensitivity: 75.00%, specificity: 56.52%), and DL model (AUC: 0.80, sensitivity: 85.71%, specificity: 69.57%). The combination of the DL and the Toronto score resulted in a significantly higher predictive performance (AUC = 0.84, sensitivity: 83.33%, specificity: 78.26%), compared with Mayo I (p = 006), Mayo II (p = 022), and Toronto score (p = 0.029). CONCLUSIONS: The combination of the DL model, based on nonenhanced cine CMR images and the Toronto score yielded significantly higher diagnostic performance in detecting HCM mutations. KEY POINTS: • Deep learning method could enable the extraction of image features from cine images. • Deep learning method based on cine images performed better than established scores in identifying HCM patients with positive genotypes. • The combination of the deep learning method based on cine images and the Toronto score could further improve the performance of the identification of HCM patients with positive genotypes.

Patients who do not fulfill criteria for hypertrophic cardiomyopathy but have unexplained giant T-wave inversion: a cardiovascular magnetic resonance mid-term follow-up study.

BACKGROUND: Patients who have unexplained giant T-wave inversions but do not meet criteria for hypertrophic cardiomyopathy (HCM) (left ventricular (LV) wall thickness < 1.5 cm) demonstrate LV apical morphological features that differ from healthy subjects. Currently, it remains unknown how the abnormal LV apical morphology in this patient population changes over time. The purpose of this study was to investigate LV morphological and functional changes in these patients using a mid-term cardiovascular magnetic resonance (CMR) exam. METHODS: Seventy-one patients with unexplained giant T-wave inversion who did not fulfill HCM criteria were studied. The mean interval time of the follow-up CMR was 24.4 ± 8.3 months. The LV wall thickness was measured in each LV segment according to the American Heart Association 17-segmented model. The apical angle (ApA) was also measured. A receiver operating curve (ROC) was used to identify the predictive values of the CMR variables. RESULTS: Of 71 patients, 16 (22.5%) progressed to typical apical HCM, while 55 (77.5%) did not progress to HCM criteria. The mean apical wall thickness was significantly different between the two groups at both baseline and follow-up, with the apical HCM group having greater wall thickness at both time points (all p < 0.001). There was a significant difference between the two groups in the change of ApA (- 1.5 ± 2.7°/yr vs. - 0.7 ± 2.0°/yr, p < 0.001) over time. The combination of mean apical wall thickness and ApA proved to be the best predictor for fulfilling criteria for apical HCM with a threshold value of 8.1 mm and 90° (sensitivity 93.8%, specificity 85.5%). CONCLUSIONS: CMR metrics identify predictors for progression to HCM in patients with unexplained giant T-wave inversion.

Early detection of left atrial dysfunction assessed by CMR feature tracking in hypertensive patients.

OBJECTIVES: To evaluate whether early left atrial (LA) dysfunction in hypertension (HTN), with or without left ventricular hypertrophy (LVH), can be detected by cardiovascular magnetic resonance feature tracking (CMR-FT). METHODS: Seventy-three HTN patients and 29 healthy controls were retrospectively recruited. HTN patients were divided into the LVH (n = 29) and non-LVH group (n = 44). LA performance was analysed using CMR-FT in 2- and 4-chamber cine images, including LA reservoir function (total ejection fraction [EF], total strain [εs], peak positive strain rate [SRs]), conduit function (passive EF, passive strain [εe], peak early negative strain rate [SRe]) and booster pump function (booster EF, active strain [εa], late peak negative strain rate [SRa]). One-way analysis of variance with post hoc LSD tests, Spearman analysis, receiver operating characteristic curve and intra-class correlation coefficient analysis were applied for statistical analyses. RESULTS: Compared with healthy controls, LA reservoir (LA total EF, εs, SRs) and conduit function (LA passive EF, εe, SRe) were significantly impaired in HTN patients with or without LVH, and these parameters significantly correlated with mitral E/A < 1 (all p < 0.05). However, LA booster pump function was relatively preserved in non-LVH patients, representing an intermediate stage between the LVH group and controls. Among LA deformation parameters, εe showed the highest diagnostic value for differentiation of HTN patients with healthy controls (AUC, 0.82; sensitivity, 80.82%; specificity, 72.41%). Observer reproducibility was good-excellent (ICC, 0.83-0.97) for all CMR-FT derived parameters. CONCLUSIONS: CMR-FT is a promising tool for quantification of LA function. LA reservoir and conduit dysfunction might be detected early by CMR-FT in HTN patients before the presence of LVH. KEY POINTS: • CMR-FT is a promising tool in quantifying LA function, including deformation and volumetric parameters. • LA reservoir and conduit dysfunction might be detected early by CMR-FT in HTN patients with or without LVH. • The LA booster pump function was relatively preserved in non-LVH patients.