Bioinformatics Analysis on lncRNA and mRNA Expression Profiles for Novel Biological Features of Valvular Heart Disease with Atrial Fibrillation

The biological features of the valvular heart disease with atrial fibrillation(AF-VHD)remain unknown when involving long non-coding RNAs(lncRNAs).This study performed system analysis on lncRNA and messenger RNA(mRNA)expression profiles constructed by using bioinformatics methods and tools for biological features of AF-VHD.Fold change and t-test were used to identify differentially expressed(DE)lncRNAs and mRNAs.The enrichment analysis of DE mRNAs was performed.The subgroups formed by lncRNAs and nearby mRNAs were screened,and a transcriptional regulation network among lncRNAs,mRNAs,and transcription factors(TFs)was constructed.The interactions between mRNAs related to lncRNAs and drugs were predicted.The 620 AF-VHDrelated DE lncRNAs and 452 DE mRNAs were identified.The 3 lncRNA subgroups were screened.The 665 regulations mediated by lncRNAs and TFs were identified.The 9 mRNAs related to lncRNAs had 1 or more potential drug interactions,totaling 37 drugs.Of these,9 drugs targeting 3 genes are already known to be able to control or trigger atrial fibrillation(AF)or other cardiac arrhythmias.The found biological features of AF-VHD provide foundations for further biological experiments to better understand the roles of lncRNAs in development from the valvular heart disease(VHD)to AF-VHD.

Clinical, sonographic characteristics and long-term prognosis of valvular heart disease in elderly patients

Background Valvular heart disease(VHD)is expected to become more prevail as the population ages and disproportionately affects older adults.However,direct comparison of clinical characteristics,sonographic diagnosis,and outcomes in VHD patients aged over 65 years is scarce.The objective of this study was to evaluate the differences in clinical characteristics and prognosis in two age-groups of geriatric patients with VHD.Methods We retrospectively enrolled consecutive individuals aged>65 years from Guangdong Provincial Peopled Hospital and screened for VHD using transthoracic echocardiography(TTE)or transesophageal echocardiography(TEE).Finally,260(48.9%)patients were in the 65-74 years group,and 272(51.1%)were in the>75-year group.Factors that affected long-term survival was explored.A multivariable Cox hazards regression was performed to identify the predictors of major adverse cardiac events(MACEs)in each group.Results In our population,the older group were more likely to have chronic obstructive pulmonary disease(COPD),degenerative VHD,but with less rheumatic VHD,aortic stenosis(AS)and mitral stenosis(MS).Compared with those aged 65-74 years,the older group had a higher incidence of all-cause death(10.0%vs.16.5%,P=0.027),ischemic stroke(13.5%vs.20.2%,P=0.038)and MACEs(37.3%vs.48.2%,P=0.011)at long-term follow-up.In multivariable Cox regression analysis,mitral regurgitation,a history of COPD,chronic kidney disease,diabetes,hypertension,atrial fibrillation and New York Heart Association(NYHA)functional class were identified as independent predictors of MACEs in the older group.Conclusion Advanced age profoundly affect prognosis and different predictors were associated with MACEs in geriatric patients with VHD.

TLR2 was overexpressed independent of IL-6 in patients with valvular atrial fibrillation

Toll-like receptor 2 （TLR2） has recently been shown to be up-regulated in patients with non-valvular atrial fi-brillation （AF）. The present study was aimed to determine whether the pathogenesis and development of AF is associated with the up-regulation of TLR2. Clinical data and right atrial appendage （RAA） specimens were col-lected from 20 patients with persisten AF （PeAF）, 15 patients with paroxysmal AF （PaAF） and 13 patients with no history of AF undergoing valvular replacement. The results showed that gene expression and protein content of TLR2 were increased in both the AF subgroups, compared with the sinus rhythm （SR） group. Between the two AF subgroups, PaAF had a higher TLR2 level than PeAF. However, no difference in interluekin （IL）-6 content was found among the three groups, and no correlation was found between TLR2 and IL-6 in PeAF patients （r = 0.090, P = 0.706）, PaAF patients （r = 0.408, P = 0.131） and AF patients （r = -0.301, P = 0.079）. Immunohistochemical analysis revealed that TLR2 was distributed in RAAs of AF patients and confirmed the immunoblotting results. In conclusion, we demonstrated that TLR2 was elevated in AF （especially PaAF） patients with valvular heart disease, further implicating inflammation involved in the pathogenesis and development of AF.

Aortic valve stenosis provides complementary information to bleeding risk scores in non-valvular atrial fibrillation patients initiating anticoagulation

Background The identification of modifiable bleeding risk factors may be of relevance.The aim is to evaluate if aortic stenosis(AS)provides additional information to bleeding risk scores for predicting major bleeding(MB)in non-valvular atrial fibrillation(AF).Methods We designed a retrospective multi-center study including 2880 consecutive non-valvular AF patients initiating oral anticoagulation between January 2013 and December 2016.AS was defined as moderate or severe according to European echocardiography guidelines criteria.HASBLED,ATRIA and ORBIT scores were used to evaluate the bleeding risk.MB was defined according to the International Society on Thrombosis and Haemostasia criteria and registered at 18 months of follow-up.Results 168(5.8%)patients had AS.Patients with AS had higher risk for MB compared to those without AS(HR=2.13,95%CI:1.40-3.23,P<0.001).Patients without AS and low-intermediate bleeding risk(0 points)showed the lowest MB rate,whereas the MB rate observed among patients with AS and high bleeding risk(2 points)was the highest one.Discrimination and reclassification analyses showed that AS provided additional information to bleeding risk scores for predicting MB at 18 months of follow-up.Conclusions In this population,AS was associated with an increased risk for MB at midterm follow-up.The three scoring systems showed a moderate discriminatory ability for MB.Moreover,the addition of AS was associated with a significant improvement in their predictive accuracy.We suggest that the presence of this valvulopathy should be taken into account for bleeding risk assessment.

Rate of anticoagulant use, and factors associated with not prescribing anticoagulant in older Thai adults with non-valvular atrial fibrillation: A multicenter registry

Objectives To investigate the rate of anticoagulant use,the reasons for not prescribing anticoagulant,and the factors associated with non-prescription of anticoagulant in older Thai adults with non-valvular atrial fibrillation.Methods A multicenter registry of patients with non-valvular atrial fibrillation was conducted during 2014 to 2017 in Thailand.Demographic,medical history,antithrombotic medication,non-antithrombotic medication,and laboratory data were collected and analyzed.Data were compared between the older adult (≥ 65 years) and younger adult (< 65 years) groups.The reasons why anticoagulant was not prescribed were collected,and predictive factors were identified.Results A total of 3218 patients (1873 males) with an average age of 67.3 ± 11.3 years were included.Almost two-thirds (61.0%) of patients were in the older adult group.Anticoagulant was prescribed in 2422 patients (75.3%): 81.4% in the older adult group and 65.7% in the younger adult group.The three main reasons for not prescribing anticoagulant were already taking antiplatelets,patient refusal,and bleeding risk.These reasons were more common in older adults as compared to younger adults.Multivariate analysis revealed current use of antiplatelets to be the most important factor that predict the non-prescription of anticoagulant in older population.Conclusions The prevalence of anticoagulant prescription among older Thai adults with atrial fibrillation is 81.4%.Taking antiplatelet drugs was found to be the strongest reason that predicts the non-prescription of anticoagulant in this patient population.A guideline should be developed to optimize the use of anticoagulant and antiplatelet in older adults.

Multiple left ventricular myxomas combined with severe rheumatic valvular lesions: A case report

BACKGROUND Primary cardiac tumors are uncommon,of which cardiac myxoma accounts for 50%-80%.Left ventricular myxoma has been rarely reported,accounting for only 3%-4%of all cardiac myxomas.Multiple left ventricular myxomas are,relatively,even rarer.CASE SUMMARY In this report,we present a case of multiple left ventricular myxomas combined with severe rheumatic valve lesions.Symptomatically,the patient presented with fatigue,shortness of breath,and palpitation after activities.The patient underwent complete surgical resection of multiple left ventricular myxomas combined with mechanical replacement of the mitral and aortic valves,tricuspid valvuloplasty.The patient recovered well after the operation,with no obvious related complications.CONCLUSION Multiple left ventricular myxomas may coexist with severe rheumatic valve disease.Operation is an effective treatment.

THE VALUE OF^(99m) Tc-MIBI MYOCARDIAL PERFUSION SPECT IMAGING IN DETECTING CORONARY ARTERY DISEASE IN PATIENTS WITH VALVULAR DISEASE BEFORE OPERATION

The aim of this study was to detect coronary artery disease using 99m Tc MIBI myocardial perfusion imaging in patients with valvular disease. [WT5”BX]Methods.[WT5”BZ] Thirty patients with valvular disease confirmed by echocardiography underwent 99m Tc MIBI myocardial perfusion imaging using multiSPECT 1h after stress test (exercise, dipyridamole or dobutamine test) and were performed coronary angiography within 1 month before valvular operation. [WT5”BX]Results.[WT5”BZ]For 29 out of the 30 patients, the results of 99m Tc MIBI myocardial perfusion imaging were similar with those of coronary angiography, the concordance rate was 96 7% and the negative predictability was 100%. [WT5”BX]Conclusion.[WT5”BZ] 99m Tc MIBI myocardial perfusion imaging is a reliable non invasive method for detecting coronary artery disease in patients with valvular disease and so as to draw up suitable operation programs for them.

Differentiation of Mouse Fibroblasts into Valvular Endothelial Cell Like Cells

The technology of induced pluripotent stem cell(iPSCs)has enabled the conversion of somatic cells into primitive undifferentiated cells via reprogramming.This approach provides possibilities for cell replacement therapies and drug screening,but the potential risk of tumorigenesis hampers further development and application.How to generate required differentia-ted cells without initiating tumor progression remains a huge challenge.Here we show that mouse embryonic fibroblasts could be differentiated into valvular endothelial cell(VEC)like cells.VECs are critical in valve replacements in aortic valve failure.VEC-associated gene and protein expression and functional assays were quantified for these VEC-like cells.We show that mouse embryonic fibroblasts could be converted into VEC-like cells.Our results suggest that it is possible to convert mouse embryonic fibroblasts into VEC-like cells without first reprogramming them into pluripotent stem cells,minimizing the possibility of tumorigenesis.

Valvular Heart Disease and Aortic Dilatation

The case presented here offers us an opportunity to discuss an increasingly commonly confronted clinical challenge.Two issues are raised:how best to manage the patient’s valvular heart disease,including both the indications for surgical intervention and the prosthetic options,and how best to manage his aortic dilatation.Let us take them one at a time.The patient has severe aortic regurgitation but a normal ejection fraction.Although we do not have his ventricular dimensions,he has a class I indication for intervention given his symptoms.

Application of Color Doppler Ultrasonic Examination in Deep Vein Valvular Incompetence in Lower Limbs

By use of color Doppler Flow Imaging (CDFI), the morphologic and hemodynamic parameters such as the diameters of femoral and popliteal veins,blood flow velocity and the reflux 0f valve area were examined in lower extremity deep valvular incompetence (DVI) and normal control gr0ups. The purpose was to evaluate the value of CDFI in the diagnosis of DVI. The results demonstrated that the parameters between the two groups had a very significant difference (P<0. 001), indicating that the CDFI is non-invasive, cost-effective and safe and it might serve as a practical tool in the diagnosis of lower extremity deep va1vular incompetence.

Rheumatic valvular heart disease treated with traditional Chinese medicine:A case report

BACKGROUND Rheumatic heart disease(RHD)is an autoimmune disease that leads to irreversible valve damage and heart failure.Surgery is an effective treatment;however,it is invasive and carries risks,restricting its broad application.Therefore,it is essential to find alternative nonsurgical treatments for RHD.CASE SUMMARY A 57-year-old woman was assessed with cardiac color Doppler ultrasound,left heart function tests,and tissue Doppler imaging evaluation at Zhongshan Hospital of Fudan University.The results showed mild mitral valve stenosis with mild to moderate mitral and aortic regurgitation,confirming a diagnosis of rheumatic valve disease.After her symptoms became severe,with frequent ventricular tachycardia and supraventricular tachycardia>200 beats per minute,her physicians recommended surgery.During a 10-day preoperative waiting period,the patient asked to be treated with traditional Chinese medicine.After 1 week of this treatment,her symptoms improved significantly,including resolution of the ventricular tachycardia,and the surgery was postponed pending further follow-up.At 3-month follow-up,color Doppler ultrasound showed mild mitral valve stenosis with mild mitral and aortic regurgitation.Therefore,it was determined that no surgical treatment was required.CONCLUSION Traditional Chinese medicine treatment effectively relieves symptoms of RHD,particularly mitral valve stenosis and mitral and aortic regurgitation.

Noninvasive Surrogates for Left Ventricular Filling Pressure in Patients with Valvular Heart Disease

Background: Invasive measurement of left ventricular filling pressure is the gold standard for determining diastolic dysfunction and predicting subsequent outcomes. For repetitive assessment of diastolic function during long-term management, noninvasive surrogates are used. Their reliability and reproducibility should be validated separately for different cardiovascular diseases and conditions. The aim of this study was to identify noninvasive surrogates of invasively derived left ventricular filling pressure and to relate these surrogates to outcomes (death or valve replacement) in patients with stable, asymptomatic valvular heart disease and preserved ejection fraction. Materials and Methods: In a first cohort, we investigated 54 patients who had spiroergometry, echocardiography, and left heart catheterization within a range of 100 days. In a second cohort (n = 64), noninvasive measures were related to outcomes after follow-up of 694 ± 576 days. Transmitral doppler E/tissue doppler E’ (E/E’), E/flow propagation velocity (E/Vp), isovolumetric relaxation time/time to E’-time to E (IVRT/TE’-TE), ventilatory efficiency (VE/VCO2slope), O2 consumption at anaerobic threshold and at peak exercise (VO2AT, VO2peak) as well as NT-pro brain natriuretic peptide (NTpro-BNP) were assessed in relation to left ventricular filling pressure and outcome. Results: NT-proBNP, VO2AT, VE/VCO2slope as well as echocardiographic surrogates E/E’ and E/flow propagation velocity were indicators of elevated end diastolic filling pressure. In multivariable analysis, VO2AT was the only independent predictor. NT-proBNP was the only surrogate of left ventricular filling pressure which predicted outcome. Conclusion: In patients with asymptomatic valvular heart disease and preserved systolic function, spiroergometric parameters and NT-proBNP performed best to assess filling pressure. Only NT-proBNP showed prognostic value in this cohort.

One Case of Diabetes Nephropathy Stage V, Combined Valvular Disease, Total Heart Failure with Diabetes Foot Gangrene

The patient was found to have 4+urine sugar by physical examination 14 years ago and was treated with oral hypoglycemic drugs. Insulin was injected intramuscularly nine years ago. Two and a half years ago, it was found that the color of the thumb, index and middle toe of the left foot became black. He went to a third-class hospital in Beijing and was diagnosed as “diabetes foot”. He was treated with “balloon dilation of lower limb blood vessels of diabetes foot”. Half a year ago, the third toe on the right side was broken and treated in the hospital again. “Popliteal artery stent implantation” was given for the diagnosis of “double kidney insufficiency, diabetes foot, left heart failure, combined heart valve disease”, “Hemofiltration therapy” and anti-inflammatory, amino acid supplementation, kidney function protection, anticoagulation, anemia correction and other treatments. Later, he went to our hospital and was diagnosed by the TCM diagnosis: category of consumptive disease, toe or finger gangrene (syndrome/pattern of qi and yin deficiency). Western medicine diagnosed: stage V of diabetes nephropathy, type II diabetes foot gangrene, combined with heart valve disease, hypoalbuminemia, double kidney cyst, moderate anemia, pleural effusion, hyperkalemia, pulmonary infection, and total heart failure. The patient was treated by the Qi-acupuncture therapy of TCM in combination with Chinese and Western medicine Medical treatment made the patient significantly better and discharged.

Advances in the pathogenesis and ultrasonic diagnosis of senile calcific valvular disease of the heart

Objective:Senile calcific valvular disease of the heart is an endemic valvular heart disease in the elderly patients. The disease is mainly characterized by degenerative change, thickening, fibrosis and calcification of the valvular connective tissue, which leads to the dysfunction of the valve and its stent. The pathogenesis of calcified valvular heart disease has not been fully elucidated, and it may be related to hemodynamics, atherosclerosis and sex. Echocardiography is the basic method and important basis for clinical diagnosis of calcified valvular heart disease, and it might detect the valvular thickening or calcification. This article aimed to analyze the pathogenesis of senile calcified valvular heart disease. At the same time, this research tried to review the progress on ultrasonic diagnosis of senile calcified valvular heart disease in order to provide references for clinical diagnosis and treatment.

Analysis of the Impact Factors on a Stable Warfarin Dose in Extreme Elderly (Age ≥ 80 Years) Chinese Patients with Non-Valvular Atrial Fibrillation

Purpose: The aim of this study was to investigate non-genetic and genetic factors contributing to stable warfarin dose change in the extreme elderly patients with non-valvular atrial fibrillation. Methods: A total of 40 elderly patients with stable warfarin doses were included in this study. Clinical basic data, such as age, sex, body mass index, basic disease like hypertension, diabetes and coronary heart disease had been recorded. Two nucleotide polymorphisms about VKORC1-1639G^A and CYP2C9 1075A^C genes were detected via sequencing by hybridization. Results: The elderly patients with CYP2C9 1075A^C (CA) genotype needed less warfarin daily doses than those?with CYP2C9 1075A^C (AA) genotype (1.93 ± 0.79 mg/d VS 2.15 ± 0.64 mg/d), but there was no significant difference (p = 0.601). While the daily warfarin dose required for patients with VKORC1-1639G^A (AA) genotype was significantly lower than that for patients with VKORC1-1639G^A (GA) genotype (2.00 ± 0.67 mg/d VS 2.63 ± 0.38 mg/d, p = 0.012). VKORC1-1639G^A together with age and diabetes status accounted 41.7% for dose variability. The new algorithm was developed using multivariate linear regression analysis;the model was developed for: Dose = 7.731 – 0.056 * age + 0.527 * DM - 0.785 * VKORC1. Conclusions: VKORC1-1639G^A together with age and diabetes status might predict warfarin doses in age ≥ 80 years patients with non-valvularatrial fibrillation. In contrast, the polymorphism of CYP2C9 1075A^C was not associated with dose variability.

Atrial Myocardial Deformation Changes in Patients with Non-Valvular Atrial Fibrillation

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. It increases cardiovascular morbidity, especially embolic stroke and mortality. Two-dimensional speckle tracking echocardiography (2D STE) is a useful method that has been used to detect changes in atrial myocardial deformation in AF patients. Objectives: To study atrial myocardial deformation changes in patient with non-valvular AF using 2D STE. Patients and Methods: This study included 25 patients with non-valvular AF and 25 normal healthy controls. 2D STE was used for assessment of strain and strain rate of septal and free walls of both right atrium (RA) and LA and left ventricle (LV). Results: Mean LA septal and lateral strain and strain rate were significantly reduced in the AF group compared to the control group (-7.2% ± 5.2% vs. -20.4% ± 3.9%, -8.7% ± 8.8% vs. -21.7% ± 3.4%) and (-0.9 ± 0.5 S-1 vs. -1.9 ± 0.4 S-1, –1.1 ± 0.6 S-1 vs. -2.04 ± 0.3 S-1) respectively. Mean RA septal and lateral strain and strain rate were significantly reduced in the AF group compared to the control group (-5.9% ± 6.1% vs. -23.4% ± 4.5%, -8.9% ± 9.3% vs. -21.7% ± 3.4%) and (-0.98 ± 0.6 S-1 vs. -1.9 ± 0.3 S-1, -1.3 ± 0.9 S-1 vs. -2.1 ± 0.5 S-1) respectively. Mean LV global longitudinal strain (GLS) and strain rate were significantly reduced in the AF group compared to the control group (-8.8% ± 4.6% vs -19.6% ± 2.4%) and (-0.8 ± 0.3 S-1 vs -1.5 ± 0.4 S-1) respectively (P < 0.001 for all). Conclusion: AF is a bi-atrial disease, LA and RA myocardial deformation properties as well as LV GLS and strain rate measured by 2D STE were significantly impaired in AF patients compared to healthy controls.

Study of Coronary Artery Disease in Single Aortic Valvular Disease

Objectives To analyze the results of coronary angiographies (CAG) in patients with single aortic valvular heart disease; To study the relationship between aortic valve diseases and coronary artery disease (CAD). Methods 105 patients with single aortic valvular heart disease before surgery underwent angiography. The data of clinical characteristics and angiographies were analyzed. Results 51 patients had symptoms of angina pectoris among 105 patients with single aortic valvular heart disease. Seven of them were confirmed coronary artery disease by angiographies. Although the incidence of angina in aortic valve stenosis group was significantly higher than that in aortic valve regurgitation, the probability of combination of CAD in aortic valve stenosis group was similar to the later. However, the probability of combination of CAD in degenerative aortic valve group was significantly higher than the groups of rheumatic, congenitally bicuspid aortic valves, and other causes (p < 0.01 ). Conclusions Angina pectoris is not sensitive for diagnosis of CAD in single aortic valve heart disease. The probability of combination of CAD in degenerative aortic valve disease is higher than that in aortic valve disease with other causes. Coronary angiography is strongly suggested for these patients.

Epidemiological survey of valvular heart disease for five years in a single cardiovascular center of Southern China: Changes in morbidity, etiological spectrum and management

Background Valvular heart disease （VHD） is defined as a structural or functional abnormality in cardiac valve which encompasses a number of common cardiovascular conditions. This study was aimed to analyze the epidemiological changes of VHD in a single cardiovascular center of Southern China. Methods A total of 13,138 VHD patients of Guangdong general hospital from January 2011 to December 2013 were screened by transthoracic echocardiography （TTE） or transesophageal echocardiography （TEE） and enrolled for this study. The morbidity, etiological spectrum and management of these patients were analyzed. Continuous variables were expressed as mean _＋ standard deviation. Categorical variables were expressed as ratio or percentage. Results Patients in this study were divided into different groups and were analyzed throughout changes in morbidity, etiological spectrum and management. Conclusions The prevalence of VHD remains high in Southern China and RHD is still the leading etiology of VHD. But morbidity rate is reduced and surgery is still the main treatment option.

Percutaneous balloon aortic valvuloplasty in the treatment of congenital valvular aortic stenosis in children

Objective To assess the effect of the balloon valvuloplasty for congenital valvular aortic stenosis (AS) in children.Methods A total of 27 (mean age 6.09 years) children with AS accepted the treatment of percutaneous balloon aortic valvuloplasty (PBAV). The ratios of balloon/valve were 0.95 ± 0.08 for 19 cases of typical AS and 1.00 ± 0.11 for 8 cases of hypoplastic AS. The patients were evaluated by the gradients across aotic valves in pre- and post-PBAV and by echocardiogram during the follow-up period.Results Fifteen of 19 (78.9％)cases of typical AS had a batter outcome and the gradient of the remaining 4 cases (26.7％) had increased after follow-up (△P ＞ 50 mm Hg) . Four of 8 (50.0％) cases of hypoplastic AS had satisfactory responses and the gradient of the remaining 3 cases (75.0％) rose. There was no moderate to severe aortic insufficiency (Al).Conclusion The balloon aortic valvuloplasty provides safe and significant hemodynamic and clinical improvement in pediatric patients. The outcome of PBAV for typical AS is better than for hypoplastic AS.

Sudden cardiac death and valvular pathology

Sudden death due to valvular heart disease is reported to range from 1% to 5% in native valves and around 0.2%-0.9%/year in prosthesis.The nature of the diseases is varied,from heritable,congenital to acquired.It may affect both genders in multiple age groups.The authors show and comment examples of the major nosologic aetiologies underlying unexpected exitus letalis of valvular nature.