Secondary leaflet tethering in patients with severe degenerative mitral regurgitation and its association with the severity of mitral regurgitation.

BACKGROUND: The purpose of the study was to determine the association between vena contracta area (VCA) and secondary leaflet tethering among mitral valve prolapse (MVP) patients, and thus to further identify and characterize an MVP with pathological leaflet tethering (MVPt+) phenotype. METHODS: We prospectively evaluated 94 consecutive MVP patients with significant mitral regurgitation (MR) and 21 healthy controls. MVPt+ group was defined as tenting volume index (TVi) > .7 mL/m2 . The three-dimensional (3D) geometry of mitral valve apparatus and VCA was measured with dedicated quantification software. RESULTS: Of the 94 patients with MVP and significant MR, 31 patients showed a TVi > .7 mL/m2 and entered the MVP with leaflet tethering (MVPt+) group. In stepwise multivariate analysis, only prolapse volume index and TVi were independently associated with 3D VCA. 3D VCA, annular area index, and plasma levels of NT-proBNP were independently correlated with the severity of leaflet tethering. ROC curve revealed that a 3D VCA ≥ .55 cm2 is the optimal cutoff point to predict MVPt+ phenotype. CONCLUSIONS: Secondary leaflet tethering is a significant mechanism behind severe degenerative MR, resulting in an MVPt+ phenotype featuring more advanced morphological and hemodynamical characteristics.

Sinus of Valsalva Aneurysm in Females.

Sinus of Valsalva aneurysm (SVA) is a rare cardiovascular disease with male predominance. Recently, an association with aortic aneurysm and SVA has been revealed in periventricular nodular heterotopia patients with loss-of-function Filamin A (FLNA) mutations, which were located on chromosome X and almost exclusively affect females.Among patients hospitalized for aortic surgery with aortic root diameter over 4.0 cm, next-generation sequencing was performed to investigate 30 candidate genes related to inherited aortic aneurysm syndromes and familial thoracic aortic aneurysm and dissection. The present report reviewed an electronic case database and identified two female cases of unruptured SVA with heterozygous FLNA truncating mutations.Case 1 displaying a rare SVA phenotype involving left and noncoronary sinus harbored a nonsense variant p.Tyr1720Ter/c.5160C > G. Case 2 displayed right and noncoronary SVA with predominantly enlarged right coronary sinus, posterior mitral valve prolapse, and harbored a frameshift variant p.Val1724fs*68/c.5171_5172delTG. Both novel mutations resulted in the premature termination of filamin A with the loss of functional Rod 2 and dimerization region.The present report raised the possibility of the presence of a cardiovascular onset form in the spectrum of FLNA hereditary diseases. The association between SVA and loss-of-function FLNA mutations indicates a unique etiology and pathogenesis among female patients, which requires further investigation to establish the linkage between FLNA variants and a wide spectrum of phenotypes.

Recurrent germline mutations as genetic markers for aortic root dilatation in bicuspid aortic valve patients.

Bicuspid aortic valve (BAV) is characterized by elevated risk of aortic dilatation and aneurysm. Although genetic susceptibility is suspected to influence on the development of BAV aortopathy, clinical application of genetic markers still needs validation in BAV entities with strictly defined phenotypic features. The 'root phenotype' represents a young, male predominant, and severely aortic regurgitant BAV population prone to aortic root dilatation. The present study launched a two-step genetic survey to evaluate the clinical significance of germline genetic markers in BAV patients. The whole-exome sequencing (WES) cohort consisted of 13 BAV patients with 'root phenotype' under the age of 40 years. We identified 28 different heterozygous missense mutations in 19 genes from the WES cohort, among which six variants (COL1A2 R882C, COL5A1 I1161F, ACVRL1 R218W, NOTCH1 P1227S, MYLK S243W, MYLK D717Y) were identified as pathogenic variants via unanimous agreement of in silico prediction tool analysis, and three variants (C1R I345L, TGFBR2 V216I, FBN2 G475V) were identified as recurrent variants. The panel of nine genetic markers was tested in an independent validation cohort of 154 BAV patients consecutively included from January to May 2018 in our institution. The validation cohort demonstrated 71.4% male predominance and the average age of 57 ± 13 years, among which 26.6% showed aortic root dilatation and 66.9% ascending aortic dilatation. Genetic markers were found in 32 patients, including 18 with C1R I345L, 11 with TGFBR2 V216I, 2 with FBN2 G475V, and 1 with both TGFBR2 V216I and MYLK D717Y. BAV patients carrying these genetic markers demonstrated younger age [(51 ± 12) vs. (58 ± 13) years, P = 0.014], more moderate to severe aortic regurgitation (56.2% vs. 33.6%, P = 0.019), elevated prevalence of mitral valve prolapse (9.4% vs. 0.8%, P = 0.028) and aortic root dilatation (62.5% vs. 17.2%, P < 0.001) but not ascending aortic dilatation than those without these markers. The early-onset 'root phenotype' entities displayed great value for BAV genetic surveys. As one of the promising complements of the current risk stratification system, recurrent germline mutations in TGFBR2, C1R, FBN2 genes could be identified and applied as genetic markers of elevated susceptibility for aortic root but not ascending aortic dilatation among BAV patients.

Cardiac angiosarcoma: A case report and review of the literature.

Primary cardiac tumors are extremely rare, among which malignancies comprise about 15-25%. As the most common type of primary cardiac malignancies, angiosarcomas tend to arise in the right heart, especially right atrium. In this case report, we presented a 32-year-old female with primary cardiac angiosarcoma in the right atrial appendage detected by transesophageal echocardiography, as it is difficult to display on conventional transthoracic echocardiography.

Distribution Patterns of Valvular and Vascular Complications in Bicuspid Aortic Valve.

For its high occurrence and elevated risks for aortic valve dysfunction and vascular complications, bicuspid aortic valve (BAV) represents a great health challenge. However, the prevalence and clinical features of BAV in the Chinese population are inadequately illustrated.From January 2011 to December 2015, 3,673 BAV patients with 69.1% male predominance were identified among 325,910 recipients of transthoracic echocardiography in our institution, demonstrating 58.4% overt aortic valve dysfunction, 52.5% ascending aortic dilatation, and 19.2% aortic root dilatation. The prevalence of pure aortic stenosis and mixed aortic valve dysfunction rose strikingly with age (both P < 0.0001), while pure aortic regurgitation showed significant decrease with age (P < 0.0001). Males showed elevated prevalence of pure aortic regurgitation (OR 3.16, 95% CI 2.55-3.91, P < 0.0001) and mixed aortic valve dysfunction than females (OR 1.63, 95% CI 1.23-2.17, P = 0.0008), but lower prevalence of pure aortic stenosis (OR 0.51, 95% CI 0.43-0.60, P < 0.0001). Aortic root dilatation was associated with male gender (OR 5.02, 95% CI 3.74-6.74, P < 0.0001), pure aortic regurgitation (OR 2.61, 95% CI 2.15-3.17, P < 0.0001), and right-left (RL) cusp fusion type (OR 1.98, 95% CI 1.64-2.40, P < 0.0001). Ascending aortic dilatation was associated with an elder age (OR 1.04, 95% CI 1.04-1.05, P < 0.0001), pure aortic stenosis (OR 1.37, 95% CI 1.16-1.61 P = 0.0002), and mixed aortic valve dysfunction (OR 2.51, 95% CI 1.89-3.33, P < 0.0001).Bicuspid aortic stenosis and ascending aortic dilatation demonstrate a similar pattern of age escalation, while aortic regurgitation is more prevalent in younger BAV patients. Aortic root dilatation intervenes closely with a unique phenotypic subgroup of male BAV patients with pure aortic regurgitation and RL fusion type.

Carbohydrate-based vaccines for oncotherapy.

Cancer is still one of the most serious threats to human worldwide. Aberrant patterns of glycosylation on the surface of cancer cells, which are correlated with various cancer development stages, can differentiate the abnormal tissues from the healthy ones. Therefore, tumor-associated carbohydrate antigens (TACAs) represent the desired targets for cancer immunotherapy. However, these carbohydrate antigens may not able to evoke powerful immune response to combat with cancer for their poor immunogenicity and immunotolerance. Different approaches have been developed to address these problems. In this review, we want to summarize the latest advances in TACAs based anticancer vaccines.

Circulating matrix metalloproteinase patterns in association with aortic dilatation in bicuspid aortic valve patients with isolated severe aortic stenosis.

Bicuspid aortic valve (BAV) exhibits a clinical incline toward aortopathy, in which aberrant tensile and shear stress generated by BAV can induce differential expression of matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs). Whether stenotic BAV, which exhibits additional eccentric high-velocity flow jet upon ascending aorta and further worsens circumferential systolic wall shear stress than BAV with echocardiographically normal aortic valve, can lead to unique plasma MMP/TIMP patterns is still unknown. According to their valvulopathy and aortic dilatation status, 93 BAV patients were included in the present study. Group A (n = 37) and B (n = 28) comprised severely stenotic patients with or without ascending aorta dilatation; Group C (n = 12) and D (n = 16) comprised echocardiographically normal BAV patients with or without ascending aorta dilatation. Plasma MMP/TIMP levels (MMP-1, -2, -3, -8, -9, -10, -13 and TIMP-1, -2, -4) were determined via a multiplex ELISA detection system in a single procedure. Among patients with isolated severe aortic stenosis, plasma levels of MMP-2 and -9 were significantly elevated when ascending aortic dilatation was present (p = 0.001 and p = 0.002, respectively). MMP-2, however, remained as the single elevated plasma component among echocardiographically normal BAV patients with dilated ascending aorta (p = 0.027). Multivariate analysis revealed that MMP-2 and MMP-9 could both serve as independent risk factor for aortic dilatation in the case of isolated severe stenosis (p = 0.003 and p = 0.001, respectively), and MMP-2 in echocardiographically normal patients (p = 0.002). In conclusion, BAV patients with isolated severe aortic stenosis demonstrated a distinct plasma MMP/TIMP pattern, which might be utilized as circulating biomarkers for early detection of aortic dilatation.

[A retrospective comparative study of acute type A aortic dissection in patients with Marfan syndrome and bicuspid aortic valves].

OBJECTIVE: To compare the clinical features of type A aortic dissection (AAD) in patients with Marfan syndrome (MFS) and bicuspid aortic valves (BAV). METHODS: Data from patients undergoing surgery for acute AAD between April 2008 and April 2012 at our institute were retrospectively collected. Patients were categorized into MFS group (n = 39) and BAV group (n = 28) to investigate their clinical and prognostic features. RESULTS: Patients in MFS and BAV groups always experienced the sudden onset of chest pain. MFS patients tended to have younger age [(35 ± 8) y vs (47 ± 13) y, P < 0.001], wider aortic sinus [(55.4 ± 9.8) mm vs (42.6 ± 8.6) mm, P < 0.01] and higher rate of moderate-to-severe aortic regurgitation (69.2% vs 32.1%, P = 0.003). Patients in BAV group were featured with higher rate of moderate-to-severe aortic stenosis. Though the operation procedures were similar in both groups, the 30-day postoperative mortality was significantly higher among BAV patients (25.0% vs 5.1%, P = 0.020). CONCLUSIONS: MFS and BAV represent unique subgroups of acute type A aortic dissection. BAV-associated dissection demonstrated strikingly higher postoperative mortality in our study population.

Pro-angiogenic cytokine features of left ventricular remodeling in patients with bicuspid aortic valve.

OBJECTIVE: Bicuspid aortic valve (BAV) is prone to promote left ventricular remodeling (LVR), which is associated with adverse clinical outcomes. Although the association between angiogenic activity and LVR has been established, pro-angiogenic cytokine features and potential biomarker candidates for LVR in patients with BAV remain to be clarified. METHODS: From November 2018 to May 2019, patients with BAV diagnosed by transthoracic echocardiography at our institution were included. LVR was diagnosed on the basis of echocardiographic calculations of relative wall thickness (RWT) and left ventricular mass index (LVMI). A multiplex ELISA array was used to measure the plasma levels of 60 angiogenesis-related cytokines. RESULTS: Among 103 patients with BAV, 71 were categorized into the LVR group and 32 into the normal left ventricular (LV) geometry group. BAV patients with LVR demonstrated increased LVMI, elevated prevalence of moderate to severe aortic stenosis and aortic regurgitation, and decreased LV ejection fraction (LVEF). Plasma levels of angiopoietin-1 were elevated in BAV patients with or without LVR compared with healthy controls (P = 0.001, P < 0.001, respectively), and were negatively correlated with RWT (r = -0.222, P = 0.027). Plasma levels of angiopoietin-2 were elevated in the LVR group (P = 0.001) compared with the normal LV geometry group, and were negatively correlated with LVEF (r = -0.330, P = 0.002). CONCLUSION: Decreased angiogenesis plays a crucial role in the occurrence and progression of LVR in patients with BAV. Disturbance in the pro- and anti-angiogenesis equilibrium in BAV patients with LVR may reflect the aggravation of endothelial injury and dysfunction.

Transesophageal echocardiography guidance for percutaneous closure of PFO and a new method to improve the diagnosis and safety during the procedures.

Purpose: Percutaneous patent foramen ovale (PFO) closure is becoming more and more common for the treatment or prevention of PFO-associated right-to-left shunt (RLS). This study aims to investigate the value of transesophageal echocardiography (TEE) in percutaneous PFO closure, and to explore a new method that can improve intraoperative diagnosis and surgical safety. Materials and methods: Based on our inclusion and exclusion criteria, we enrolled 73 patients between 16 and 70 years old (average age 43.25 ± 14.87 years) who underwent percutaneous PFO closure at the Department of Cardiac Surgery, Zhongshan Hospital (Xiamen), Fudan University, from January 2022 to December 2023. Out of the 73 enrolled patients, there were 28 males (38.36%) and 45 females (61.64%), 29 migraine patients (39.73%), 14 patients (19.19%) with headache and dizziness, 14 patients (19.18%) with a history of cerebral infarction (CI), and 25 patients (34.25%) with CI, lacunar infarction or ischemic focus on magnetic resonance imaging (MRI). All patients received routine transthoracic echocardiography (TTE) and agitated saline contrast echocardiography (ASCE) before operations. Percutaneous closure of PFO was completed under the guidance of TEE. In 12 patients, the method of "injection of heparinized sterile saline through the delivery sheath" was used to observe their RLS, and the anatomical characteristics of the PFO according to the shunt path were monitored and evaluated. This method was also applied to some patients to guide the conveyor to pass through the foramen ovale (FO) channel safely and effectively, thereby improving the success rate of PFO closure. Results: The application of TEE during the procedure of percutaneous PFO closure, including preoperative evaluation, intraoperative guidance, and postoperative reevaluation, can offer further details about the anatomical and shunt characteristics of PFO, improve the diagnosis rate, and confirm the safety of the surgical path. It ensures the safety and reliability of the whole operation, greatly improving the success rate and reducing postoperative complications. Conclusions: TEE guidance of percutaneous PFO closure has the advantages of minimal trauma, no radiation and real-time visualization, while injecting heparinized sterile saline through the delivery sheath is safer and more effective in improving the success rate and reducing postoperative complications.

Characteristic of myocardial work in mitral valve prolapse with versus without mitral annular disjunction: A propensity-matched study.

BACKGROUND: Mitral annular disjunction (MAD) tends to coexist with mitral valve prolapse (MVP) and mitral regurgitation (MR), and is also highly associated with arrhythmias. Myocardial work (MW) analysis is dedicated to estimate myocardial performance by integrating strain analysis and afterload. We aimed to use MW analysis to investigate the cardiac remodeling and dysfunction in MAD, particularly the damage of some segments, and to enhance the understanding of the correlations between MW parameters and VAs within MVP patients. METHODS: A total of 22 consecutive MVP patients with MAD (MAD+) and 44 consecutive MVP patients without MAD (MAD-) (50 ± 11yeas; 18% females) were screened by propensity score matching (PSM), and were divided into subgroups based on MR severity (MR+: Grade 2+; MR-: ≤1), GWI median (GWI ≤ 2079.5 mmHg%; GWI>2079.5 mmHg%), as well as the presence of VAs (VAs+; VAs-). MW parameters consist of global work efficiency (GWE), global work index (GWI), global constructive work (GCW) and global wasted work (GWW). RESULTS: The MAD+ patients had larger LVEDD and LAVI, as well as lower GWE, GWI, and GCW (all P<0.05) compared to the MAD- patients, regardless of similar GLS and regurgitant volume(both P>0.05). When categorized by MR severity, GWI (P = 0.049) and GCW (P = 0.040) were diminished in the MR-MAD+ group. The regional analysis showed MAD+ patients had decreased MW index in the basal (posterior and inferior) and mid (posterior and inferior) segments. Multivariate linear regression showed MAD phenotype, but not MR severity, was independently associated with diminished GWE, GWI, and GCW (all P<0.05). When divided by GWI median, MAD phenotype [OR (95%CI): 5.189 (1.193-22.572), P = 0.028] was an independent predictor of decreased GCW. The receiver-operating characteristic curve identified bileaflet prolapse [AUC (95%CI): 0.664 (0.502-0.825), P = 0.045], and GWI for basal inferior [(AUC (95%CI): 0.679 (0.538-0.819), P = 0.020] as the predictors of the VAs. CONCLUSION: MAD phenotype has the ability to compromise cardiac structure and function, irrespective of volume overload, as evidenced by dilated LV and impaired MW index in basal and mid segments. Excessively decreased regional MW index can identify patients with the high risk of VAs. MW analysis can be a valuable imaging marker for detecting myocardial impairment induced by MAD.

Feasibility validation of automatic diagnosis of mitral valve prolapse from multi-view echocardiographic sequences based on deep neural network.

Aims: To address the limitations of traditional diagnostic methods for mitral valve prolapse (MVP), specifically fibroelastic deficiency (FED) and Barlow's disease (BD), by introducing an automated diagnostic approach utilizing multi-view echocardiographic sequences and deep learning. Methods and results: An echocardiographic data set, collected from Zhongshan Hospital, Fudan University, containing apical 2 chambers (A2C), apical 3 chambers (A3C), and apical 4 chambers (A4C) views, was employed to train the deep learning models. We separately trained view-specific and view-agnostic deep neural network models, which were denoted as MVP-VS and MVP view-agonistic (VA), for MVP diagnosis. Diagnostic accuracy, precision, sensitivity, F1-score, and specificity were evaluated for both BD and FED phenotypes. MVP-VS demonstrated an overall diagnostic accuracy of 0.94 for MVP. In the context of BD diagnosis, precision, sensitivity, F1-score, and specificity were 0.83, 1.00, 0.90, and 0.92, respectively. For FED diagnosis, the metrics were 1.00, 0.83, 0.91, and 1.00. MVP-VA exhibited an overall accuracy of 0.95, with BD-specific metrics of 0.85, 1.00, 0.92, and 0.94 and FED-specific metrics of 1.00, 0.83, 0.91, and 1.00. In particular, the MVP-VA model using mixed views for training demonstrated efficient diagnostic performance, eliminating the need for repeated development of MVP-VS models and improving the efficiency of the clinical pipeline by using arbitrary views in the deep learning model. Conclusion: This study pioneers the integration of artificial intelligence into MVP diagnosis and demonstrates the effectiveness of deep neural networks in overcoming the challenges of traditional diagnostic methods. The efficiency and accuracy of the proposed automated approach suggest its potential for clinical applications in the diagnosis of valvular heart disease.

Mendelian randomization indicates that atopic dermatitis contributes to the occurrence of diabetes.

BACKGROUND: An association has been indicated between atopic dermatitis (AD), a prevalent chronic inflammatory skin disease, and diabetes mellitus. However, the exact causal relationship between AD and both type 1 diabetes (T1D) and type 2 diabetes (T2D) remains controversial. This study aimed to explore the causal association between AD and diabetes by Mendelian Randomization (MR) approaches. METHODS: Public genetic summary data for AD was obtained from EAGLE study. Single nucleotide polymorphisms of diabetes were retrieved from four genome-wide association studies that had been performed in European populations. Inverse variance weighted (IVW) in MR analysis was used as the primary means of causality estimation. Several complementary analyses and sensitivity analyses were performed to calculate MR estimates and to enhance the causal inference, respectively. The R package 'TwoSampleMR' was used for analysis. RESULTS: Genetically predicted AD led to a higher risk of T1D (OR, 1.19; 95% CI, 1.05, 1.34; P = 0.006) and T2D (OR, 1.07; 95% CI, 1.02, 1.11; P = 0.003) based on random-effect IVW method. The complementary analyses provided similar positive results. Cochran's Q test and I2 statistics indicated moderate heterogeneity between AD and both T1D and T2D. No significant horizontal pleiotropy was detected by MR-Egger Intercept p except summary data from FinnGen consortium. CONCLUSION: Genetically predicted AD is a risk factor for both T1D and T2D. These findings imply potential shared pathological mechanisms between AD and diabetes, thus suggesting the significance of early clinical diagnosis and prevention of AD in reducing the incidence of diabetes.

Analysis of the Spatial Distribution Characteristics of Crude Oils with Different Freezing Points and the Genetic Mechanism of High-Freezing-Point Crude Oils in the Dongying Sag.

The freezing point of crude oils is an important factor affecting the process of exploration, development, and transportation of crude oils. In the Dongying Sag, the freezing point of crude oils varies greatly in space, and high-freezing-point crude oils have been found in many structural belts. The freezing point of crude oils in the Dongying Sag is generally high, ranging from -40 to 80 °C. The distribution of high-freezing-point crude oils in the Dongying Sag is scattered, and they have been found at different depths, layers, and structural belts, with relatively more occurrences in specific areas. Based on the relationship between the wax content and the resin + asphaltene content, the high-freezing-point crude oils in the Dongying Sag can be classified into three types (type A, type B, and type C). Type A, type B, and type C high-freezing-point crude oils are mainly found in the gentle slope zone, depression zone, and uplift zone, respectively. The contents of wax and resins + asphaltenes in crude oils are the key factors controlling the freezing point of crude oils in the Dongying Sag. Oil source correlation using biomarkers and n-alkane carbon isotopes demonstrates that different types of high-freezing-point crude oils are generated from different source rocks, indicating that the source of crude oils is not the only factor controlling the freezing point of crude oils. The hydrocarbon-generating parent material of hydrocarbon source rocks developed in different depositional environments of the Dongying Sag is generally characterized by the dominance of bacteria and algae and is supplemented by terrestrial higher plants. This lays the material foundation for the formation of waxes during the maturation of hydrocarbon source rocks. The change of temperature and pressure conditions during the process of oil expulsion from source rocks and migration in the carrier bed will lead to phase fractionation and composition changes of oils, thus forming type A freezing point crude oils in the slope zone and type B freezing point oils in the depression zone. The increase in resin and asphaltene content caused by biodegradation and water washing in shallower buried oil reservoirs is the reason for the formation of type C high-freezing-point crude oils. The research results indicate that the organic matter composition and hydrocarbon alteration during migration and accumulation jointly control the formation of high-freezing-point crude oils in lacustrine basins. The extensive input of terrestrial organic matter into the source rocks of the lacustrine basin laid the foundation for the formation of high-freezing-point crude oils, and the migration fractionation and biodegradation of the crude oils further promoted the formation of high-freezing-point crude oils.

Left ventricular myocardial work for the prediction of postoperative outcomes in patients with bicuspid aortic stenosis.

Chronic elevation of left ventricular (LV) afterload contributes to adverse LV remodeling and myocardial impairment in bicuspid aortic valve (BAV) patients with severe aortic stenosis (AS). Incorporating LV afterload into global longitudinal strain (GLS) analysis, myocardial work facilitates early detection of LV dysfunction. The present study was to evaluate myocardial work in BAV patients with severe AS undergoing surgical aortic valve replacement (SAVR) and to evaluate its prognostic impact on early postoperative outcomes. Between January 2021 and March 2022, BAV patients with severe AS scheduled for SAVR were included and underwent comprehensive transthoracic echocardiography. Quantification of LV myocardial work was performed to obtain LV global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Clinical outcome was defined as a composite of major cardiovascular events including mortality, myocardial infarction, stroke, acute kidney injury, low cardiac output syndrome and vascular complications during hospitalization or within 30 days after operation. Among 103 BAV patients with severe AS undergoing SAVR (mean age of 65 ± 9 years, 57.3% male), 22 experienced postoperative major cardiovascular events. BAV patients with major cardiovascular events demonstrated lower LV GWI (P < 0.001) and GCW (P = 0.002) along with elder age (P = 0.030), decreased LVGLS (P = 0.026) and right ventricular longitudinal strain (P = 0.019), and higher prevalence of abnormal average E/e' ratio (P = 0.029) than those without major events. Decreased LV GWI and GCW was independently associated with the occurrence of major cardiovascular events (P < 0.01 for adjusted OR). Multivariable logistic regression model including LV GWI demonstrated superior power than the model including LVGLS and yielded best discrimination for BAV patients with and without major cardiovascular events during early postoperative period. Echocardiography-based LV myocardial work overcomes the limitations of LVGLS and presents as a promising novel index for the early detection of functional myocardial damage and the optimization of intervention timing among BAV patients with severe AS.

Prognostic role of aortic distensibility in patients with bicuspid aortic valve: a CMR study.

To evaluate the prognostic value of aortic distensibility measured by cardiovascular magnetic resonance (CMR) as predictors of prophylactic aortic valve or aortic surgery in patients with bicuspid aortic valve (BAV). 110 patients with BAV were included. Distensibility of middle ascending aorta (AscAo) and proximal descending aorta (DescAo) at baseline was determined using CMR. The association between aortic distensibility and primary endpoint of aortic valve and/or aortic surgery was investigated with Cox proportional hazard regression analyses. The receiver operating characteristics curves (ROC) of the area under receiver-operator (AUC) and DeLong test were used to evaluate and compare the performance of different models. During a median follow-up of 66.5 months [IQR 13-75 months], 42 patients experienced surgical treatments. After adjusting for traditional risk factors, aortic distensibility (P = 0.003) and severe valve dysfunction (P < 0.001) were found significantly associated with aortic valve and/or aortic surgery. The model 2 (aortic distensibility and severe valve dysfunction) is slightly better in predicting primary endpoint than the model 1 (aortic diameter and severe valve dysfunction) (AUC: 0.893 vs. 0.842, P = 0.106). In BAV patients, aortic distensibility and severe valve dysfunction are valuable predictors for final aortic valve and/or aortic surgery.

Application of myocardial work in predicting adverse events among patients with resistant hypertension.

BACKGROUND: Hypertension is the most common chronic disease and the leading risk factor for disability and premature deaths worldwide. Approximately 10-20% of all patients with hypertension and 15-18% of the general population who are treated for hypertension have resistant hypertension (RH). Patients with RH have a higher risk of end-organ damage, such as carotid intima-media thickening, retinopathy, left ventricular hypertrophy and heart failure, myocardial infarction, stroke, impaired renal function, and death than those with controlled blood pressure. In the present study, we applied echocardiography to patients with RH to evaluate myocardial work (MW) and determine whether it is predictive for the occurrence of adverse events within 3 years. METHODS: We included 283 outpatients and inpatients aged ≥ 18 years who met the clinical criteria for RH, without arrhythmia and severe aortic valve stenosis, between July 2018 and June 2019. The patients were followed up for 3 years from starting enrollment, and any adverse event that occurred during the period was used as the observation end point. Each enrolled patient underwent a complete transthoracic echocardiogram examination, blood pressure was measured and recorded, and MW was then analyzed. RESULTS: Eighty-two (28.98%) patients with RH had adverse events, such as myocardial infarction (n = 29, 35.36%), heart failure (n = 4, 0.05%), renal insufficiency (n = 40, 48.78%), renal failure (n = 2, 0.02%), cerebral infarction (n = 5, 0.06%), and cerebral hemorrhage (n = 2, 0.02%), and no death events occurred. In patients with RH and adverse events, global longitudinal strain (GLS) (- 16% vs. - 18%), the global work index (2079 mmHg% vs. 2327 mmHg%), global constructive work (2321 mmHg% vs. 2610 mmHg%), and global work efficiency (93% vs. 94%) were lower than those in patients without adverse events. However, global wasted work (GWW) was higher in patients with RH and adverse events than in those without adverse events (161 mmHg% vs. 127 mmHg%). GLS and GWW were the most significant in predicting adverse events. CONCLUSIONS: MW, especially GLS and GWW, is a good method to predict 3-year adverse events in patients with RH.

Echocardiographic parameters recommended for assessing the severity of tricuspid regurgitation: concordance and discordance.

Background: Current guidelines recommend integrating several echocardiographic indices to evaluate the severity of tricuspid regurgitation (TR). Discordance of indices, including qualitative and quantitative methods, commonly exists in practice. The discordance among these parameters has not yet been fully elucidated. Methods: A total of 127 patients with recognizable TR jets without pulmonary regurgitation or intracardiac shunt were prospectively enrolled. We evaluated 8 parameters by 2-dimensional (2D) echocardiography: proximal iso-velocity surface area (PISA)-derived regurgitant volume (RVol), PISA-derived effective regurgitant orifice area (EROA), PISA radius, vena contracta width (VCW), color Doppler jet area, tricuspid valve annular diameter, inferior vena cava (IVC) diameter, and peak E wave. According to current guidelines, each echocardiographic parameter was determined to represent either severe or non-severe TR. A concordance score was calculated as the number of concordant parameters divided by 8, with a higher score reflecting better concordance. Data were further categorized into 3 subgroups: complete concordance (0 discordant parameters), high concordance (1-2 discordant parameters), and low concordance (3-4 discordant parameters). Results: The mean concordance score was 81%±17% for the entire cohort. There were 48 (38%) patients with complete concordance, including 6 patients with severe TR. In contrast, the low concordance group (n=43, 34%) mostly comprised severe TR patients (36 patients). When considering only EROA, RVol, and VCW, concordance improved, with 98 patients (77%) in complete agreement. Conclusions: Concordance seems limited when using echocardiographic parameters to assess TR severity. Applying only EROA, RVol, and VCW results in better concordance, as recommended by the current guidelines.

Activation of the Hedgehog signaling pathway leads to fibrosis in aortic valves.

BACKGROUND: Fibrosis is a pathological wound healing process characterized by excessive extracellular matrix deposition, which interferes with normal organ function and contributes to ~ 45% of human mortality. Fibrosis develops in response to chronic injury in nearly all organs, but the a cascade of events leading to fibrosis remains unclear. While hedgehog (Hh) signaling activation has been associated with fibrosis in the lung, kidney, and skin, it is unknown whether hedgehog signaling activation is the cause or the consequence of fibrosis. We hypothesize that activation of hedgehog signaling is sufficient to drive fibrosis in mouse models. RESULTS: In this study, we provide direct evidence to show that activation of Hh signaling via expression of activated smoothened, SmoM2, is sufficient to induce fibrosis in the vasculature and aortic valves. We showed that activated SmoM2 -induced fibrosis is associated with abnormal function of aortic valves and heart. The relevance of this mouse model to human health is reflected in our findings that elevated GLI expression is detected in 6 out of 11 aortic valves from patients with fibrotic aortic valves. CONCLUSIONS: Our data show that activating hedgehog signaling is sufficient to drive fibrosis in mice, and this mouse model is relevant to human aortic valve stenosis.