SCN11A gene deletion causes sensorineural hearing loss by impairing the ribbon synapses and auditory nerves.

BACKGROUND: The SCN11A gene, encoded Nav1.9 TTX resistant sodium channels, is a main effector in peripheral inflammation related pain in nociceptive neurons. The role of SCN11A gene in the auditory system has not been well characterized. We therefore examined the expression of SCN11A in the murine cochlea, the morphological and physiological features of Nav1.9 knockout (KO) ICR mice. RESULTS: Nav1.9 expression was found in the primary afferent endings beneath the inner hair cells (IHCs). The relative quantitative expression of Nav1.9 mRNA in modiolus of wild-type (WT) mice remains unchanged from P0 to P60. The number of presynaptic CtBP2 puncta in Nav1.9 KO mice was significantly lower than WT. In addition, the number of SGNs in Nav1.9 KO mice was also less than WT in the basal turn, but not in the apical and middle turns. There was no lesion in the somas and stereocilia of hair cells in Nav1.9 KO mice. Furthermore, Nav1.9 KO mice showed higher and progressive elevated ABR threshold at 16 kHz, and a significant increase in CAP thresholds. CONCLUSIONS: These data suggest a role of Nav1.9 in regulating the function of ribbon synapses and the auditory nerves. The impairment induced by Nav1.9 gene deletion mimics the characters of cochlear synaptopathy.

Percutaneous closure of the left atrial appendage: The value of real time 3D transesophageal echocardiography and the intraoperative change in the size of the left atrial appendage.

OBJECTIVE: The aim of this study was to investigate the value of real time three-dimensional transesophageal echocardiography (RT3DTEE) in percutaneous closure of the left atrial appendage (LAAC). In addition, this study also explored the change in the size of the left atrial appendage (LAA) from 24 hours before the operation to just before implantation during the operation. METHODS AND RESULTS: In a retrospective study, 32 patients underwent two-dimensional transesophageal echocardiography (2DTEE) and RT3DTEE 24 hours prior to operation and during operation. The maximal LAA orifice diameter (by 2DTEE, 22.7 ± 2.7 vs 24.6 ± 2.2 mm, P < 0.01; by RT3DTEE, 24.2 ± 2.9 vs 25.8 ± 2.7 mm, P < 0.01), the maximal landing zone diameter (by 2DTEE, 19.0 ± 2.8 vs 20.4 ± 2.8 mm, P < 0.01; by RT3DTEE, 20.4 ± 2.7 vs 22.6 ± 3.0 mm, P < 0.01), and the maximal depth diameter (by 2DTEE, 25.2 ± 3.2 vs 26.5 ± 3.0 mm, P < 0.01; by RT3DTEE, 26.4 ± 3.2 vs 27.5 ± 3.7 mm, P < 0.01) all increased significantly during the operation. The highest correlation (R) between the maximal landing zone diameter and the compressed occluder diameter was determined for RT3DTEE measurements during the operation (R = 0.90), whereas the landing zone diameter (R = 0.80) measured by 2DTEE was less correlated. In addition, our study showed that RT3DTEE was of great value in discriminating the LAA orifice shape, allowing differentiation of the LAA morphology and identification of the number of LAA lobes. CONCLUSIONS: A certain amount of intravenous rehydration just before and during operation increased the LAA size significantly. The measurements by RT3DTEE showed a closer correlation to LAA occluder size than those by 2DTEE. The LAA displayed by RT3DTEE was more visible than that by 2DTEE.

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.

Assessment of left atrial mechanical function and synchrony in paroxysmal atrial fibrillation with two-dimensional speckle tracking echocardiography.

BACKGROUND: The aim of this study was to investigate left atrial (LA) function and synchrony in paroxysmal atrial fibrillation (PAF) patients using two-dimensional speckle tracking echocardiography (STE). METHODS: Forty-five PAF patients and 30 healthy controls were enrolled. LA peak ventricular systolic longitudinal strain (LAS-S ) and strain rate (LASR-S ) and left atrial longitudinal strain (LAS-A ) and strain rate (LASR-A ) during late diastole were determined using STE, and the standard deviation of the time to peak (TPSD) of the regional strains was calculated to quantify LA dyssynchrony. TPSD during ventricular systole and late diastole were named SDs and SDa, respectively. RESULTS: Left atrial peak longitudinal strain during ventricular systole (LAS-S ) (29.34±8.57 vs 36.73±6.13), LASR-S (1.27±0.311 vs 1.57±0.25), LAS-A (13.11±4.91 vs 17.86±3.57), and LASR-A (-1.51±0.58 vs -1.90±0.30) were reduced in the PAF group compared with the controls (P<.05 for all). SDs (8.11±3.00% vs 4.67±1.48%) and SDa (5.57±2.26% vs 3.11±1.13%) were greater in PAF patients than in the controls (P<.05 for both). Furthermore, PAF patients with normal LA sizes exhibited lower LAS-S (P<.05), LASR-S (P<.05), LAS-A (P<.05), and LASR-A (P<.05) values and increased SDs (P<.05) and SDa (P<.05) values compared with the controls. Multivariate regression confirmed that SDs and SDa were powerful parameters for differentiating PAF patients from controls (SDs: sensitivity, 83%; specificity, 72%; SDa: sensitivity, 81%; specificity, 76%). CONCLUSIONS: Left atrial (LA) dysfunction and dyssynchrony in PAF patients can be detected with STE even in the absence of LA enlargement. STE-derived SDs and SDa were powerful parameters for identifying PAF patients.

A de novo silencer causes elimination of MITF-M expression and profound hearing loss in pigs.

BACKGROUND: Genesis of novel gene regulatory modules is largely responsible for morphological and functional evolution. De novo generation of novel cis-regulatory elements (CREs) is much rarer than genomic events that alter existing CREs such as transposition, promoter switching or co-option. Only one case of de novo generation has been reported to date, in fish and without involvement of phenotype alteration. Yet, this event likely occurs in other animals and helps drive genetic/phenotypic variation. RESULTS: Using a porcine model of spontaneous hearing loss not previously characterized we performed gene mapping and mutation screening to determine the genetic foundation of the phenotype. We identified a mutation in the non-regulatory region of the melanocyte-specific promoter of microphthalmia-associated transcription factor (MITF) gene that generated a novel silencer. The consequent elimination of expression of the MITF-M isoform led to early degeneration of the intermediate cells of the cochlear stria vascularis and profound hearing loss, as well as depigmentation, all of which resemble the typical phenotype of Waardenburg syndrome in humans. The mutation exclusively affected MITF-M and no other isoforms. The essential function of Mitf-m in hearing development was further validated using a knock-out mouse model. CONCLUSIONS: Elimination of the MITF-M isoform alone is sufficient to cause deafness and depigmentation. To our knowledge, this study provides the first evidence of a de novo CRE in mammals that produces a systemic functional effect.

Different Combinations of Right Ventricular Longitudinal Velocity and Displacement Can Be Applied Effectively for Diagnosis of Right Heart Failure in Chinese Patients.

BACKGROUND: The noninvasive evaluation of right ventricular function (RVF) in cardiovascular and pulmonary diseases remains a challenge. Internationally recommended echocardiographic parameters for the evaluation of RVF may not be applicable to China, because of the limited examination time per patient, the varying skill levels of ultrasonographers, inadequate allocation of professional specialties, and outdated instruments and equipment. METHODS: Sixty-two patients admitted for right heart failure and 52 healthy volunteers were included in the analysis. The tricuspid annular plane systolic excursion (TAPSE), peak systolic velocity in the tricuspid annulus of the right ventricular free wall (S'), myocardial performance index, right ventricular fractional area change, and Doppler peak strains in the base and mid cavity were evaluated and compared between groups. RESULTS: Compared with the control group, all RVF parameters in the right heart failure group showed significant deterioration (P < .001). However, only TAPSE and S' were finally included in the discriminant equation. The diagnostic cutoff values derived from the receiver operating characteristic curve were <13.74 mm and <9.5 cm/s, respectively. The highest specificity in the diagnosis of right heart failure (100%) was achieved using S' <9.5 cm/s, either alone or in combination with TAPSE <13.74 mm. The highest diagnostic sensitivity (90.32%) was achieved using either TAPSE <13.74 mm or S' <9.5 cm/s alone. CONCLUSION: TAPSE and S' are more suitable than other parameters for the diagnosis of right heart failure in Chinese patients. Different combinations of TAPSE and S' can be applied effectively for the diagnosis of right heart failure.

Prognostic Value of Speckle Tracking Echocardiography in Patients with ST-Elevation Myocardial Infarction Treated with Late Percutaneous Intervention.

BACKGROUND: Left ventricular remodeling (LVr) is common after ST-segment elevation myocardial infarction (STEMI). The aim of this study was to evaluate the prognostic value of speckle tracking echocardiography (STE) for predicting LVr 6-9 months after late percutaneous coronary intervention (PCI) in patients with STEMI. METHODS: Patients with first STEMI who accepted late PCI were enrolled. Echocardiography was performed within 48 hours of admission. Six to nine months after MI, an echocardiography examination was repeated. LVr was defined as >15% increase in LV end-systolic volume (LVESV) after 6 months. RESULTS: One hundred and twenty-seven patients were divided into two groups: 86 patients without LVr and 41 patients with LVr. There were significant differences in the global longitudinal strain (GLS), SD of time to peak longitudinal systolic strain (longitudinal Ts-SD), longitudinal postsystolic index, radial strain (RS), and SD of time to peak radial systolic strain (Radial Ts-SD). In multivariate logistic regression analysis, the GLS(odds ratio [OR] = 0.39, 95% confidence interval [CI] = 0.26-0.57, P < 0.01), and RS(OR = 1.07, 95% CI = 1.02-1.13, P = 0.01) were determinants of LVr. A receiver operating characteristic curve showed that the GLS predicted LVr with an optimal cutoff value of -10.85 (sensitivity: 89.7%, specificity: 91.7%). During clinical follow-up for 16.9 ± 1.6 months, death or congestive heart failure developed in 12 patients (9.4%), and the baseline ejection fraction (OR = 1.91, 95% CI = 1.18-3.1, P = 0.009) and GLS (OR = 0.56, 95% CI = 0.34-0.91, P = 0.02) were independent predictors. CONCLUSION: In patients with STEMI treated with late percutaneous coronary intervention, the GLS as measured by STE is a strong predictor of LVr and adverse events.

Predictive value of brachial-ankle artery pulse wave velocity to heart failure with preserved ejection fraction in hospitalised patients with acute dyspnoea.

OBJECTIVE: To explore the predictive value of the brachial-ankle artery pulse wave velocity (baPWV) for heart failure with preserved ejection fraction (HFpEF). METHODS: Echocardiographic data, B-type natriuretic peptide (BNP) level, and baPWV were assessed in 111 consecutive patients admitted for acute dyspnea. The patients were divided into the HFpEF group (n=71) and the control group (n=40). RESULTS: Multivariate logistic regression analyses revealed that the ratio of the early mitral inflow velocity to the tissue Doppler velocity (E/e') at the lateral mitral annulus, BNP, and baPWV were independently predictive of HFpEF. Adding the baPWV to E/e' at the lateral annulus and to the BNP resulted in an increase in the area under the curve (AUC) to 0.855 (vs. lateral E/e' alone, P=0.02) or 0.880 (vs. BNP alone, P=0.02), respectively. The AUC of the three combining indicators including the lateral E/e', BNP, and baPWV was 0.910 (vs. E/e' lateral alone, P<0.001; vs. BNP alone, P=0.001). The diagnostic accuracy was improved significantly after adding the baPWV to the diagnostic criteria of the 2007 ESC consensus statement (net reclassification improvement 0.127, P=0.02). CONCLUSIONS: Adding the baPWV to the current diagnostic indicators of the 2007 ESC consensus statement could increase the accuracy of predicting HFpEF.

Noninvasive assessment of left atrial phasic function in patients with hypertension and diabetes using two-dimensional speckle tracking and volumetric parameters.

OBJECTIVE: To evaluate the left atrial phasic function of hypertensive patients with or without coexisting diabetes using two-dimensional speckle tracking echocardiography (2DSTE)-based strain and strain rate imaging and volumetric parameters. METHODS: The study included an isolated hypertension group (HT group) comprising 99 patients, a hypertension and diabetes group (HT + DM group) comprising 65 patients, and 26 age-matched healthy controls. The 2DSTE-based strain and strain rate images were studied, and the following parameters were measured: peak left atrial longitudinal strain (LAS-S ), early diastolic (LAS-E ) and late diastolic (LAS-A ) atrial longitudinal strains, and systolic (LASR-S ), early diastolic (LASR-E ) and late diastolic (LASR-A ) strain rates. RESULTS: The LAS-S and LASR-S were lower in the HT group and the HT + DM group compared with the control group (P < 0.001). The LAS-E and LASR-E were lower in the HT group (14.9 ± 5.5% and -1.1 ± 0.4/sec, respectively) than in the control group (22.1 ± 8.3% and -1.7 ± 0.6/sec, respectively) (P < 0.001), and they were further depressed in the HT + DM group (12.3 ± 6.3% and -1.0 ± 0.4/sec, respectively) (P < 0.05). There were no significant differences in LAS-A or LASR-A among the 3 groups (P > 0.05). Multivariate regression analysis revealed that HT and DM were independently related to LAS-E and LASR-E . CONCLUSIONS: Hypertension can lead to abnormal left atrial reservoir and conduit functions, and coexisting diabetes can further impair conduit function. 2DSTE-derived strain and strain rate imaging are sensitive methods for evaluating left atrial phasic function.

Biomechanical comparison of anterior lumbar screw-plate fixation versus posterior lumbar pedicle screw fixation.

Anterior lumbar interbody fusion (ALIF) followed by posterior pedicle screw fixation (PSF) in a second procedure is mostly used to implement lumbar spine fusion. ALIF followed by anterior lumbar screw-plate has a lot of advantages, but its biomechanical stability requires confirmation. This study evaluated the biomechanical stability of a novel anterior lumbar locked screw-plate (ALLSP) by comparison with posterior lumbar PSF. Twelve fresh human cadaveric lumbar specimens (L4-L5) were assigned to four groups: ALIF+PSF group, ALIF+ALLSP (both fixed) group, ALIF group and an untreated control (both non-fixed) group. The first three groups received implantation of a rectangular titanium cage. Tests under axial compression, flexion, extension, lateral bending, or rotation showed that the fixed groups had significantly stronger stability than the non-fixed groups (P=0.000 for all). The ALIF+ALLSP group had significantly greater axial stiffness under applied axial compression and significantly less angular displacement under rotational forces than the ALIF+PSF group. The angular displacement of the ALIF+ALLSP group was less under flexion than that of the ALIF+PSF, and the angular displacement under lateral bending and extension was greater, but these differences were not statistically significant. In summary, the ALLSP conforms to the anterior lumbar spine and has good biomechanical stability. It is a reliable choice for enhancing the stability of ALIF.

Influence of Microalloying on the Microstructures and Properties of Spalling-Resistant Wheel Steel.

Microalloyed steels have emerged to replace conventional plain-carbon steels to achieve longer wheel life on Chinese railroads. In this work, with the aim of preventing spalling, a mechanism that consists of ratcheting and shakedown theory correlated with steel properties is systematically investigated. Mechanical and ratcheting tests were carried out for microalloyed wheel steel to which vanadium was added in the range of 0-0.15 wt.% and the results were compared with that obtained for conventional plain-carbon wheel steel. The microstructure and precipitation were characterized via microscopy. As a result, the grain size was not obviously refined, and the pearlite lamellar spacing decreased from 148 nm to 131 nm in microalloyed wheel steel. Moreover, an increase in the number of vanadium carbide precipitates was observed, which were mainly dispersed and uneven, and precipitated in the pro-eutectoid ferrite region, in contrast to the observation of lower precipitation in the pearlite. It has been found that vanadium addition can lead to an increase in yield strength by precipitation strengthening, with no reduction or increase in tensile strength, elongation or hardness. The ratcheting strain rate for microalloyed wheel steel was determined to be lower than that for plain-carbon wheel steel via asymmetrical cyclic stressing tests. An increase in the pro-eutectoid ferrite content leads to beneficial wear, which can diminish spalling and surface-initiated RCF.

Associations of brachial-ankle pulse wave velocity with left atrial stiffness and left atrial phasic function in inpatients with hypertension.

Hypertension induces left atrial (LA) and left ventricular (LV) dysfunction, and an increase in arterial stiffness. This study aimed to investigate the associations of brachial-ankle pulse wave velocity (baPWV) with LA stiffness and LA phasic function in hypertension. A total of 305 hypertensive inpatients enrolled and were divided into two groups based on baPWV [Group I, baPWV ≤ 1515 (cm/s), n = 153; Group II, baPWV > 1515 (cm/s), n = 152]. Two-dimensional speckle tracking echocardiography (2D-STE) based LA phasic strains (LAS-S, LAS-E, LAS-A) and LV global longitudinal strain (LVGLS) were evaluated. LA stiffness index (LASI) was defined as the ratio of E/e' to LAS-S. Multivariate linear regression modeling was used to analyze the associations of baPWV with LASI and LA phasic function in all patients as well as age-specific and sex-specific subgroups. LASI was significantly higher in Group II [0.35(0.26, 0.52)] compared with Group I [0.26(0.20, 0.36)] (P < 0.001). After adjusting cardiovascular risk factors, medication, and LV structural and functional parameters (LVEF, LVMI, E/A ratio, and LVGLS), baPWV remained significantly correlated with LASI (P < 0.05). We also evaluated the predictive value of baPWV for LASI, the area under the curve (AUC) was 0.663 (95% CI: 0.607-0.716, P < 0.001). In conclusion, BaPWV was independently associated with LA stiffness in hypertensive inpatients. BaPWV also exhibited a certain predictive value for LA stiffness in these inpatients. Measuring arterial stiffness can provide clinicians clues for early cardiac target organ damage (TOD) in addition to vascular TOD.

Association Between Segmental Noninvasive Myocardial Work and Microvascular Perfusion in ST-Segment Elevation Myocardial Infarction: Implications for Left Ventricular Functional Recovery and Clinical Outcomes.

BACKGROUND: Predicting left ventricular recovery (LVR) after acute ST-segment elevation myocardial infarction (STEMI) is of prognostic importance. This study aims to explore the prognostic implications of segmental noninvasive myocardial work (MW) and microvascular perfusion (MVP) after STEMI. METHODS: In this retrospective study, 112 patients with STEMI who underwent primary percutaneous coronary intervention and transthoracic echocardiography after percutaneous coronary intervention were enrolled. Microvascular perfusion was analyzed by myocardial contrast echocardiography, and segmental MW was analyzed by noninvasive pressure-strain loops. A total of 671 segments with abnormal function at baseline were analyzed. The degrees of MVP were observed following intermittent high-mechanical index impulses: replenishment within 4 seconds (normal MVP), replenishment >4 seconds and within 10 seconds (delayed MVP), and persistent defect (microvascular obstruction). The correlation between MW and MVP was analyzed. The correlation of the MW and MVP with LVR (normalization of wall thickening, >25%) was assessed. The prognostic value of segmental MW and MVP for cardiac events (cardiac death, admission for congestive heart failure, or recurrent myocardial infarction) was evaluated. RESULTS: Normal MVP was seen in 70 segments, delayed MVP in 236, and microvascular obstruction in 365. The segmental MW indices were independently correlated with MVP; 244 (36.4%) segments had segmental LVR at 3-month follow-up. Segmental MW efficiency and MVP were independently associated with segmental LVR (P < .05). The χ2 of combination of segmental MW efficiency and MVP was higher than either index alone for identifying segmental LVR (P < .001). At a median follow-up of 42.0 months, cardiac events occurred in 13 patients; all regional MW parameters, high sensitivity troponin I, regional longitudinal strain, and so on were associated with cardiac events. CONCLUSIONS: Segmental MW indices are associated with MVP within the infarct zone following reperfused STEMI. Both are independently associated with segmental LVR, and regional MW is associated with cardiac events, providing prognostic value in STEMI patients.

Clinical influencing factors affecting pulmonary hypertension in hemodialysis patients

Background: The fluid status and rate of blood flow through the arteriovenous fistula (AVF) are two important factors affecting hemodynamic in hemodialysis patients; however, their effects on pulmonary hypertension have rarely been studied. Hence, we aimed to evaluate the effects of these factors in hemodialysis patients with pulmonary hypertension. Methods: This single-center cross-sectional survey included 219 maintenance hemodialysis patients (139 [63.5%] male). The prevalence of pulmonary hypertension was 13.6% (30 of 219). Pulmonary artery pressure was measured by echocardiography, fluid status was measured objectively using bioimpedance spectroscopy, and blood flow rate in the AVF (Qa) was determined using Doppler ultrasound. Results: The overall mean overhydration before hemodialysis was 1.5 L (range, 0.6-2.8 L). The mean overhydration in patients with and without pulmonary hypertension was 3.6 L (range, 2.3-4.6 L) and 1.4 L (range, 0.6-2.4 L), respectively (p < 0.001). The overall mean Qa was 780 mL/min (range, 570-1,015.5 mL/min). The mean Qa of patients with and without pulmonary hypertension was 672 mL/min (range, 505.7-982.2 mL/min) and 790 mL/min (range, 591-1,026 mL/min), respectively (p = 0.27). Overhydration (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.08-1.97; p = 0.01), N-terminal prohormone of brain natriuretic peptide (NT-proBNP; OR, 1.36; 95% CI, 1.09-1.71; p = 0.007), and left atrial diameter (OR, 1.14; 95% CI, 1.01-1.28; p = 0.03) were risk factors. Conclusion: Pulmonary hypertension is strongly associated with overhydration, NT-proBNP, and left atrial diameter in hemodialysis patients.

Anthracycline-Induced Atrial Structural and Electrical Remodeling Characterizes Early Cardiotoxicity and Contributes to Atrial Conductive Instability and Dysfunction.

Aims: Cancer patients treated with anthracyclines are susceptible to atrial fibrillation (AF), while the mechanisms remain unclear. Due to sudden and unpredictable features, prediction of anthracycline-induced AF at early phase is difficult. Clinically, we tested whether anthracycline-induced early atrial remodeling in patients could be detected by echocardiography. Experimentally, we investigated the mechanisms of doxorubicin-induced atrial remodeling and AF in mice, and the protective effects of dexrazoxane and antioxidants. Methods and Results: Postsurgery breast cancer patients with an anthracycline-containing or anthracycline exclusion regimen were recruited for echocardiography before chemotherapy, and 3 and 6 months after chemotherapy. Mice were injected with doxorubicin or vehicle (5 mg/kg/week, 4 weeks), and left atrial diameter, electrical transmission, and AF inducibility were measured. Meanwhile, the level of reactive oxygen species (ROS), activity of antioxidant enzymes, cardiomyocyte size, vacuolization, inflammation, and fibrosis were also measured in mouse atria. The therapeutic effects of dexrazoxane and antioxidants on doxorubicin-induced changes in the aforementioned parameters were also determined. While ventricular parameters and functions were unchanged in cancer patients receiving anthracyclines before and after chemotherapy, left atrial reservoir and conduit function were decreased at 3 months postchemotherapy versus prechemotherapy. Doxorubicin-induced susceptibility to AF occurred in mice before onset of ventricular dysfunction. Doxorubicin-induced AF was via inducing structural remodeling (cardiomyocyte death, hypotrophy, and vacuolization) and electrical remodeling (reduction and redistribution of connexin 43) in atria, which was effectively prevented by dexrazoxane or antioxidants through inhibiting ROS generation or enhancing ROS elimination. Innovation and Conclusion: AF inducibility was induced after doxorubicin injection, which can be inhibited by repressing the ROS level. Antioxid. Redox Signal. 37, 19-39. The Clinical Trial Registration number is PJ-KS-KY-2019-73.

Development and Validation of a Nomogram for Estimation of Left Atrial Thrombus or Spontaneous Echo Contrast Risk in Non-Valvular Atrial Fibrillation Patients with Low to Borderline CHA2DS2-VASc Score.

Purpose: Left atrial thrombus (LAT)/left atrial spontaneous echo contrast (LASEC) still exists in CHA2DS2-VASc score-defined low/borderline risk population. The purpose of this study is to explore the risk factors that associate with LAT/SEC and to create a nomogram to predict LAT/SEC risk in NVAF patients with low/borderline CHA2DS2-VASc scores. Patients and Methods: A total of 834 NVAF patients with complete data on transesophageal echocardiography (TEE) were included in this study. Univariate and multivariate logistic regression analyses were performed to identify the risk factors that associate with LAT/SEC, and a nomogram was established based on the results. Receiver operating characteristic curve (ROC), calibration curve and decision curve analysis were performed to verify the predictive power of nomogram. Results: The rates for LAT/SEC for the training and validation cohorts were 84 (14.7%) and 30 (11.4%), respectively. Independent factors including age, left ventricular ejection fraction (LVEF), left atrial diameter (LAD), smoke, non-paroxysmal AF (NPAF), and E/e' were considered to construct the nomogram for LAT/SEC. The AUC for nomogram was 0.839 and 0.811 in the training and validation cohorts, respectively. The calibration and decision curve analysis showed that the nomogram had a good prediction capacity and would be clinically useful. Conclusion: Age, LVEF, LAD, smoke, NPAF, and E/e' are independently associated with LAT/SEC in NVAF patients with low/borderline CHA2DS2-VASc scores. The nomogram that incorporates these six variables effectively predict LAT/SEC risk in NVAF patients with low/borderline CHA2DS2-VASc scores.

Case Report: Multimodal Imaging Guides the Management of an Eosinophilic Leukemia Patient With Eosinophilic Myocarditis and Intracardiac Thrombus.

Background: Eosinophilic leukemia (EL) is a rare, serious and potentially life-threatening condition characterized by the overproduction of eosinophils leading to tissue eosinophilic infiltration and damage. Although multiple organ systems may be involved, progressive eosinophilic myocarditis (EM) is the most common cause of morbidity and mortality. Early diagnosis and follow-up surveillance combined with multimodal imaging are crucial for appropriate treatment of EM. Case Summary: It's a rare case of EL with EM and intracardiac thrombus in a 59-year-old patient who presented with asthenia for 3 weeks. Full blood count analysis indicated significant eosinophilia. Bone marrow aspirate revealed dysplastic eosinophilia and a FIP1L1-PDGFRA fusion gene (4q12) was detected, confirming EL. Echocardiography revealed EM with intracardiac thrombus. This was later confirmed by cardiac magnetic resonance imaging. The patient was commenced on imatinib and prednisolone and good clinical response was obtained. Through 18F-FAPI PET/CT imaging, we obtained in vivo visualization of fibroblast activation changes in the early stage of cardiac structure remodeling. With anti-fibrotic therapy after heart failure, the patient achieved a good clinical response. Conclusion: This case demonstrates in vivo visualization of fibroblast activation after EM. Multimodality imaging can provide early diagnosis and may guide tailored antifibrotic therapy in early stage of EM.

Evaluation of left atrial function and mechanical dispersion in breast cancer patients after chemotherapy.

BACKGROUND: Left atrial (LA) function and mechanical dispersion changes in breast cancer patients treated with chemotherapy remain unclear. HYPOTHESIS: LA function and LA mechanical dispersion in breast cancer patients would be impaired after chemotherapy. METHODS: This single-center retrospective study included 91 consecutive breast cancer patients treated with chemotherapy and 30 controls. Patients were examined by echocardiography three times at intervals. Conventional parameters, left ventricular strain, LA strain, and LA mechanical dispersion were evaluated and compared. RESULTS: LA strain during reservoir phase (LASr), conduit phase (LAScd), and contraction phase (LASct) all decreased markedly after chemotherapy and were lower than those of the controls (all p < .01). The standard deviation of time to peak positive strain during LA reservoir phase corrected by R-R interval (LA SD-TPSr) was significantly increased after chemotherapy and was higher than that of the controls (p < .001). The change of LA function was expressed as Δ. Multivariate linear regression analyses showed that LAVIp (0.399, 95% confidence interval [CI]: 0.610, 1.756, p = .000) was independently associated with ΔLASr, LAPEF (-0.325, 95% CI: -45.123, -10.676, p = .002) and age (0.227, 95% CI: 0.021, 0.350, p = .027) were independently associated with ΔLAScd, and LAVImax (0.341, 95% CI: 0.192, 0.723, p = .001) was independently associated with ΔLASct. LAVImax (0.505, 95% CI: 0.000, 0.001, p = .039) and mitral E (-0.256, 95% CI: 0.000, 0.000, p = .024）were independently associated with ΔLA SD-TPSr. CONCLUSIONS: Mechanical function of LA declined after chemotherapy in breast cancer patients. With the decrease of LA mechanical function, LA mechanical dispersion assessed by two-dimensional speckle-tracking echocardiography increased significantly, and its clinical value needs to be further studied.

Application of Rough Ant Colony Algorithm in Adolescent Psychology.

With the rapid development of big data, big data research in the security protection industry has been increasingly regarded as a hot spot. This article mainly aims at solving the problem of predicting the tendency of juvenile delinquency based on the experimental data of juvenile blindly following psychological crime. To solve this problem, this paper proposes a rough ant colony classification algorithm, referred to as RoughAC, which first uses the concept of upper and lower approximate sets in rough sets to determine the degree of membership. In addition, in the ant colony algorithm, we use the membership value to update the pheromone. Experiments show that the algorithm can not only solve the premature convergence problem caused by stagnation near the local optimal solution but also solve the continuous domain and combinatorial optimization problems and achieve better classification results. Moreover, the algorithm has a good effect on predicting classification and can provide guidance for predicting the tendency of juvenile delinquency.

Left atrial stiffness index as a marker of early target organ damage in hypertension.

This study aimed to evaluate left atrial (LA) mechanics using two-dimensional speckle-tracking echocardiography (2DSTE) and investigate their correlations with measures of target organ damage (TOD) in hypertension. We enrolled 42 healthy controls (Group I) and 286 hypertension patients: Group II (n = 79) had an LA volume index (LAVI) <28 ml/m2; Group III (n = 92) had an LAVI ≥28 ml/m2; and Group IV (n = 115) had hypertension with left ventricular hypertrophy (LVH). We measured the following parameters: LA reservoir strain and strain rate (LAS-S, LASR-S), LA conduit strain and strain rate (LAS-E and LASR-E), and LA booster strain and strain rate (LAS-A and LASR-A). The LA stiffness index (LASI) was defined as the ratio of early diastolic transmitral flow velocity/lateral mitral annulus myocardial velocity (E/e') to LAS-S. We performed correlation and regression analyses of individual TOD with LA phasic functions, the LASI, and cardiovascular risk factors. Our findings showed that there was a trend toward a gradual increase in the LASI from controls to normal LA and enlarged LA patients and finally to hypertrophic LV patients. The LASI was significantly higher in Group III [0.28 (0.20, 0.38)] than in Group I [0.20 (0.16, 0.23)] and Group II [0.22 (0.18, 0.27)] and was the highest in Group IV [0.33 (0.26, 0.43)]. The LA reservoir and conduit function gradually decreased from Group I to Group IV. Multivariate regression analysis revealed that the LASI was independently correlated with individual TOD. In conclusion, abnormal LA mechanics precede LA enlargement and LVH, and an increased LASI can be used as a marker of early TOD in hypertension.