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.

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.

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.

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.

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.

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.

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.

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.

Association of aortic distensibility and left ventricular function in patients with stenotic bicuspid aortic valve and preserved ejection fraction: a CMR study.

To determine the relationship between aortic distensibility and left ventricular (LV) remodeling, myocardial strain and blood biomarkers in patients with stenotic bicuspid aortic valve (BAV) and preserved ejection fraction (EF) by cardiovascular magnetic resonance (CMR). 43 stenotic BAV patients were prospectively selected for 3.0 T CMR. Patients were divided into LV remodeling group (LV mass/volume ≥ 1.15, n = 21) and non-remodeling group (LV mass/volume < 1.15, n = 22). Clinical characteristics, biochemical data including cardiac troponin T(cTNT), N-terminal pro-B type natriuretic peptide (NT-proBNP) and creatine kinase isoenzyme (CK-MB) were noted. Distensibility of middle ascending aorta (mid-AA) and proximal descending aorta, LV structural and functional parameters, global and regional myocardial strain were measured. Compared to non-remodeling group, LV remodeling group had significantly decreased LV global strain (radial: 26.04 ± 8.70% vs. 32.92 ± 7.81%, P = 0.009; circumferential: - 17.20 ± 3.38% vs. - 19.65 ± 2.34%, P = 0.008; longitudinal: - 9.13 ± 2.34% vs. - 11.63 ± 1.99%, P < 0.001) and decreased mid-AA distensibility (1.22 ± 0.24 10-3 mm/Hg vs 1.60 ± 0.41 10-3 mm/Hg, P = 0.001). In addition, mid-AA distensibility was independently associated with LV remodeling (ß = - 0.282, P = 0.003), and it was also significantly correlated with LV global strain (radial: r = 0.392, P = 0.009; circumferential: r = - 0.348, P = 0.022; longitudinal: r = - 0.333, P = 0.029), cTNT (r = - 0.333, P = 0.029) and NT-proBNP (r = - 0.440, P = 0.003). In this cohort with stenotic BAV and preserved EF, mid-AA distensibility is found significantly associated with LV remolding, which encouraging to better understand mechanism of ventricular vascular coupling.

Efficacy of C-Mill gait training for improving walking adaptability in early and middle stages of Parkinson's disease.

BACKGROUND: Walking adaptability is an obvious manifestation of Parkinson's disease (PD). Augmented reality technologies such as interactive walkways may improve walking adaptability in patients with Parkinson's Disease (PWP). RESEARCH QUESTION: How effective is C-Mill gait adaptability training in the early and middle stages of PD for improving walking adaptability in motor subtypes of the disease? METHODS: Fifty-two patients with early- or middle-stage PD were divided into two groups according to motor subtype (postural instability/gait disorder [PIGD] and non-PIGD) and received 7 days of training (0.5 h every day, 2 h after medication) on an augmented reality treadmill with built-in visual targets and obstacles. Functional assessments were performed before and after intervention, including posture control and walking, C-gait assessment, and participant experience. The Parkinson Disease Quality of Life questionnaire was administered at 3-month follow-up. RESULTS: Both the PIGD (n = 29) and non-PIGD (n = 23) groups showed improved tandem walking, obstacle avoidance, and overall score in C-gait assessment and Timed Up and Go test after C-Mill training. However, there were no differences between the two groups. The PIGD group showed improvement in visually guided stepping and Speed adaptations, whereas the non-PIGD group did not improve. The non-PIGD group reported they could complete the training with less exertion after the intervention and at the 3-month follow-up, these patients reported improvement in quality of life. SIGNIFICANCE: C-Mill gait adaptation training in the early and middle stages of PD improves walking adaptability in both motor subtypes. Cue strategies are the probable mechanism and may decrease fall risk after training. There was no difference between the groups in the improvements of perceived exertion and quality of life at follow-up. Although PIGD patients showed statistic improvements in visually guided stepping compared with non-PIGD patients, but the difference was not likely to be clinically meaningful. Specific effects of C-mill training for different types of PD were not observed in our study.

The association of depressive symptoms with disability among adults in China.

BACKGROUND: The symptoms that patients with major depressive disorder (MDD) experience are the dominant contributing factors to its heavy disease burden. This study sought to identify key symptoms leading to disability in patients with MDD. METHODS: Subjects consisted of patients who had a 12-month MDD diagnosis based on the China Mental Health Survey (CMHS). World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) was used to assess the degree of disability. The associations between depressive symptoms and disability were analyzed using a linear regression and logistic regression with a complex sampling design. RESULTS: Of the 32,552 community residents, 655 patients were diagnosed with 12-month MDD. The disability rate due to MDD was 1.06% (95% CI: 0.85%-1.28%) among adults in Chinese community and 50.7% (95% CI: 44.3%-57.1%) among MDD patients. Depression was associated with all functional losses measured by the WHODAS. Feelings of worthlessness in life or inappropriate guilt, and psychomotor agitation or retardation were the key symptoms related to disability. Economic status, co-morbidity of physical diseases or anxiety disorders were correlates of disability scores. LIMITATIONS: The disability rate might be underestimated due to the exclusion of MDD patients living in hospitals. The effect of treatments on disability was excluded. CONCLUSIONS: Psychological symptoms, not somatic symptoms, contribute to disability in MDD patients. Disability worsens when physical diseases or anxiety disorders are present. More attention could be paid to psychological symptoms, physical diseases, and anxiety disorders in MDD patients with disabilities.

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.

Risk assessment model for heart failure in Chinese patients with Takayasu's arteritis.

OBJECTIVES: We aimed to construct and validate a risk assessment model to identify risk factors for heart failure (HF) in patients with Takayasu's arteritis (TAK). METHODS: Three hundred sixty-five patients with TAK were recruited in the East China Takayasu Arteritis Cohort from January 2012 to December 2019. Patients were assigned into training and validation sets following a 2:1 ratio according to the date of enrollment. Clinical characteristics were compared between heart failure (HF) and non-HF subgroups in the training set, and a risk assessment model for HF and its scoring algorithm was established based on logistic regression, which was tested in the validation set. RESULTS: Among total of 74 (20.27%) TAK patients exhibited HF, and 55 cases (74.32%) were in the training set. The risk factors for HF of TAK patients included onset age >38 years, serum tumor necrosis factor (TNF)-α concentration >10 pg/ml, aortic valve involvement, coronary artery involvement, and pulmonary hypertension. We constructed the model without TNF-α (Model 1) and with TNF-α (Model 2). Patients in the training set with the score ≥ 3 appeared to be associated with an increased risk of HF with an area under curve (AUC) of 0.88 and 0.90 in Model 1 and Model 2 respectively. The AUC reached to 0.88 and 0.89 in the validation set that proved the accuracy of the model. CONCLUSIONS: We presented a risk assessment model of HF in TAK, which may help clinicians alert the complication of HF in the patients with specifically cardiac impairments. Key Points • Heart failure was not rare in Chinese Takayasu's arteritis patients, and there were approximately 20% of patients with heart failure in ECTA cohort. • Cardiac involvements on echocardiography include pathological valvular and atrioventricular abnormalities. • The onset age >38 years, serum tumor necrosis factor (TNF)-α concentration >10 pg/ml, aortic valve involvement, coronary artery involvement, and pulmonary hypertension were risk factors for heart failure in Takayasu's arteritis patients. • We constructed the model without TNF-α (Model 1) and with TNF-α (Model 2). Patients with the risk assessment model score of ≥ 3 appeared to be associated with an increased risk of heart failure.

David reimplantation with simultaneous total arch replacement and stented elephant trunk for acute type A aortic dissection.

OBJECTIVES: To compare early and mid-term outcomes between David reimplantation and the Bentall procedure with simultaneous total arch replacement (TAR) and stented elephant trunk (SET) implantation in acute type A aortic dissection (ATAAD). METHODS: From January 2012 to June 2018, 148 patients underwent aortic root replacement combined with TAR and SET for ATAAD. Patients were evaluated retrospectively and categorized into David reimplantation (n = 55) and Bentall procedure (n = 93) groups. Propensity-matched analysis was performed to compare in-hospital and follow-up adverse events between the 2 groups. RESULTS: In-hospital mortality and the incidence of major perioperative complications were comparable between the 2 groups (all P > .05). No significant difference in mean cardiopulmonary bypass time and circulatory arrest time was found between the 2 groups, although mean crossclamp time was longer in the David group (P = .02). During a follow-up period of 2.6 (interquartile range, 1.5-4.3) years, the Bentall group experienced rates of paravalvular leakage and prosthetic valve endocarditis of 2.3% and 2.3%, respectively, whereas the David group experienced rates of infective endocarditis and recurrent moderate aortic regurgitation of 1.9% and 1.9%, respectively. The overall survival was 82.9% for the David group and 89.2% for the Bentall group (P = .63), whereas the incidence of major cardiovascular-related events was 21.3% and 17.3% (P = .30) 5 years postoperatively. CONCLUSIONS: For Chinese patients undergoing ATAAD, David reimplantation provided similar outcomes compared with the Bentall procedure, with simultaneous TAR and SET. David reimplantation is an appealing option for patients who suffer root ectasia or extensive sinus damage albeit normal leaflets.

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.

Mitral valve repair for degenerative mitral regurgitation in patients with left ventricular systolic dysfunction: early and mid-term outcomes.

BACKGROUND: This study aims to evaluate the early and mid-term outcomes of mitral valve repair for degenerative mitral regurgitation (MR) in patients with left ventricular systolic dysfunction. METHODS: From January 2005 to December 2016, the profiles of patients with degenerative MR who underwent mitral valve repair at our institution were analyzed. Left ventricular systolic dysfunction was defined as an ejection fraction < 60% or left ventricular end-systolic dimension > 40 mm. Finally, 322 patients with left ventricular systolic dysfunction were included in this study. The prognosis of left ventricular function during follow-up was evaluated and preoperative factors associated with deteriorated left ventricular systolic function during follow-up were analyzed. RESULTS: The in-hospital mortality rate was 1.6%. The rate of eight-year overall survival, freedom from reoperation for mitral valve and freedom from recurrent MR were 96.9, 91.2 and 73.4%, respectively. Intraoperative residual mild MR (hazard ratio 4.82) and an isolated anterior leaflet lesion (hazard ratio 2.48) were independent predictive factors for recurrent MR. During follow-up, 212 patients underwent echocardiography examinations at our institution. Among them, 132 patients had improved left ventricular systolic function, and 80 patients had deteriorated left ventricular systolic. Freedom from recurrent MR was found in 75.9% of the improved left ventricular systolic function group and 56.2% of the deteriorated left ventricular systolic function group (P = 0.047). An age > 50 years (odds ratio 2.40), ejection fraction≤52% (odds ratio 2.79) and left ventricular end-systolic dimension≥45 mm (odds ratio 2.31) were independent risk factors for deteriorated left ventricular systolic function during follow-up. CONCLUSIONS: Mitral valve repair could be safely performed for degenerative MR in patients with left ventricular systolic dysfunction. Intraoperative residual mild MR and an isolated anterior leaflet lesion were independent predictive factors for recurrent MR. An age > 50 years, ejection fraction≤52% and left ventricular end-systolic dimension≥45 mm were independent risk factors for deteriorated left ventricular systolic function during follow-up.

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.

Aortic stenosis exacerbates flow aberrations related to the bicuspid aortic valve fusion pattern and the aortopathy phenotype.

OBJECTIVES: A bicuspid aortic valve (BAV) is characterized by variable phenotypic manifestations, as well as longitudinal evolution of valve dysfunction and ascending aorta dilatation. The present study investigated the impact of severe aortic stenosis (AS) on the flow patterns and wall shear stress (WSS) distribution in BAV patients with right-left (RL) and right-non-coronary (RN) cusp fusion types, and the study aimed to reveal whether aortic dysfunction could further alter intrinsic aortic haemodynamic aberrations generated by abnormal BAV cusp fusion patterns. METHODS: Four-dimensional flow magnetic resonance imaging was performed in 120 BAV subjects and 20 tricuspid aortic valve controls. BAV patients were evenly categorized into 4 cohorts, including RL and RN BAV with no more than mild aortic dysfunction as well as RL and RN BAV-AS with isolated severe AS. RESULTS: BAV subjects exhibited eccentric outflow jets resulting in regional WSS elevation at the right-anterior position of the ascending aorta in the RL group and the right-posterior location in the RN group (P < 0.005). The presence of severe AS resulted in accelerated outflow jets and more prominent flow and WSS eccentricity (P < 0.005) by marked helical (P = 0.014) and vortical flow formation (P < 0.005), as well as increased prevalence of tubular and transverse arch dilatation. The changes to the flow jet in BAV-AS subjects blurred the differences in peak flow velocity and WSS distribution between RL and RN BAV. Differences in the phenotypes of aortopathy were associated with changes in functional haemodynamic parameters such as flow displacement and WSS eccentricity. CONCLUSIONS: Severe AS markedly exacerbated aortic flow aberrations in BAV patients and masked the existing distinct flow features deriving from RL and RN fusion types. Longitudinal studies are needed to investigate the evolution of ascending aortic dilatation relative to the interaction between intrinsic cusp fusion types and acquired severe valve dysfunction.