Huge mediastinal ancient schwannoma causing acute respiratory failure: a case report.

Benign mediastinal tumor is usually asymptomatic and exhibits uncomplicated clinical course. Posterior mediastinal schwannoma is common, but a huge benign tumor causing acute respiratory failure due to mass effect is unusual. We present a patient who suffered from acute respiratory failure due to huge mediastinal mass effect and improved after en bloc surgical resection. A 56-year-old woman had no history of systemic disease, but experienced general discomfort and malaise for several months. She was referred to our emergency department after developing sudden respiratory failure. Intubation was performed with ventilator support and she was admitted to the intensive care unit. Chest radiograph and computed tomography showed a huge mass over the left pleural cavity causing left lung, heart, and mediastinal compression. After en bloc resection, she was weaned off the ventilator successfully and was discharged at 24 days after the operation. Postoperative outpatient follow-up showed no symptoms. Mediastinal ancient schwannoma is a rare posterior mediastinal benign tumor. However, mass effect might lead to lethal complications. En bloc resection is necessary for curative treatment.

Comparative of clinical performance between next-generation sequencing and standard blood culture diagnostic method in patients suffering from sepsis.

BACKGROUND: Next-generation sequencing (NGS) is a massively unbiased sequencing technology. The objective of this study was to evaluate the performance of NGS-based approach in the detection of microorganisms from septic patients and compare with results of blood culture (BC). METHODS: The observational and non-interventional study was conducted from April 2019 to August 2019. RESULTS: A total of 96 sets of BC and 48 NGS results obtained from 48 septic patients were analyzed in this study. Thirty-two microorganisms (27 bacteria, 3 fungi and 2 viral) were detected by NGS in 23 (47.9%) patients; and 18 bacteria in 18 (37.5%) patients by BC. Exclusion of skin commensals, the positivity of NGS and BC was 62.5% and 14.5%, respectively (P < 0.001). Microorganisms identified by NGS demonstrated positive agreement with BC in 12 (25%) patients, including concordant results in 11 (22.9%) cases, and discrepancy results in 1 (2%). Of 11 patients with concordant results, 4 had additional microorganisms detected by NGS. NGS-positive but BC-negative was found in 9 (18.7%) patients. Using NGS, difficult-to-culture micro-organisms such as Pneumocystic jirovecii was identified in 2 patients, and Leptospira interrogans in one. Six (12.5%) patients with BC-positive but NGS-negative, whereas skin commensals were isolated in 4 (66.6%) cases. The number of patients that were positive by BC only increase from 29% to 47.9% when combining NGS and BC analyses (P = 0.033). CONCLUSIONS: Our study support the advantage of NGS for the diagnosis of infecting microorganisms in sepsis, especially for microorganisms that are currently difficult or impossible to culture.

Comparable long-term results of the extracardiac conduit total cavopulmonary connection in heterotaxy to non-heterotaxy patients.

BACKGROUND: Fontan operation in heterotaxy patients has been associated with high mortality. We studied whether adoption of the extracardiac conduit (EC) total cavopulmonary connection (TCPC) in heterotaxy demonstrated comparable results to non-heterotaxy population. METHODS: A retrospective medical record review of 35 consecutive patients with heterotaxy and 70 consecutive patients without heterotaxy syndrome who underwent EC TCPC between 2000 and 2018 was performed. RESULTS: In the 35 heterotaxy patients, 30 were right and 5 were left atrial isomerism. Anomalies of venous return included bilateral superior vena cava in 20 (57.1%), separated hepatic vein in 8 (22.9%), interrupted inferior vena cava in 3 (8.6%), total anomalous pulmonary venous return in 7 (20%), and partial in 2 patients (5.7%). All patients underwent EC TCPC under beating-heart cardiopulmonary bypass except in four patients (11.4%) cardioplegic arrest was needed for cardiac repair. The surgical mortality rate was lower in heterotaxy patients (0% vs. 5.7%; p = 0.299) but statistically not significant. The follow-up ranged from 2 months to 17.8 years (mean 9.4 ± 5.6 years). At 15 years, there was no significant difference between the heterotaxy and non-heterotaxy patients regarding the long-term survival (70% vs. 78.6%; p = 0.443), freedom from reoperation (81.9% vs. 96.5%; p = 0.057), and postoperative arrhythmia (17.1% vs. 7.1%; p = 0.174). CONCLUSIONS: EC TCPC can be performed in heterotaxy patients with comparable early and late results to the non-heterotaxy population. However, the late morbidities regarding the Fontan circulation needs careful follow-up.

Idi1 and Hmgcs2 Are Affected by Stretch in HL-1 Atrial Myocytes.

BACKGROUND: Lipid expression is increased in the atrial myocytes of mitral regurgitation (MR) patients. This study aimed to investigate key regulatory genes and mechanisms of atrial lipotoxic myopathy in MR. METHODS: The HL-1 atrial myocytes were subjected to uniaxial cyclic stretching for eight hours. Fatty acid metabolism, lipoprotein signaling, and cholesterol metabolism were analyzed by PCR assay (168 genes). RESULTS: The stretched myocytes had significantly larger cell size and higher lipid expression than non-stretched myocytes (all p < 0.001). Fatty acid metabolism, lipoprotein signaling, and cholesterol metabolism in the myocytes were analyzed by PCR assay (168 genes). In comparison with their counterparts in non-stretched myocytes, seven genes in stretched monocytes (Idi1, Olr1, Nr1h4, Fabp2, Prkag3, Slc27a5, Fabp6) revealed differential upregulation with an altered fold change >1.5. Nine genes in stretched monocytes (Apoa4, Hmgcs2, Apol8, Srebf1, Acsm4, Fabp1, Acox2, Acsl6, Gk) revealed differential downregulation with an altered fold change <0.67. Canonical pathway analysis, using Ingenuity Pathway Analysis software, revealed that the only genes in the "superpathway of cholesterol biosynthesis" were Idi1 (upregulated) and Hmgcs2 (downregulated). The fraction of stretched myocytes expressing Nile red was significantly decreased by RNA interference of Idi1 (p < 0.05) and was significantly decreased by plasmid transfection of Hmgcs2 (p = 0.004). CONCLUSIONS: The Idi1 and Hmgcs2 genes have regulatory roles in atrial lipotoxic myopathy associated with atrial enlargement.

Differential Gene Expression Profile of Renin-Angiotensin System in the Left Atrium in Mitral Regurgitation Patients.

BACKGROUND: Left atrial enlargement is a mortality and heart failure risk factor in primary mitral regurgitation (MR) patients. Pig models of MR have shown differential expression of genes linked to the renin-angiotensin system. Therefore, the aim of this study was to investigate the key genes of the renin-angiotensin that are expressed differentially in the left atrial myocardium in MR patients. METHODS: Quantitative RT-PCR was used to compare gene expression in the renin-angiotensin system in the left atrium in MR patients, aortic valve disease patients, and normal subjects. RESULTS: Plasma angiotensin II concentrations did not significantly differ between MR patients and aortic valve disease patients (P = 0.582). Compared to normal controls, however, MR patients had significantly downregulated expressions of angiotensin-converting enzyme, angiotensin I converting enzyme 2, type 1 angiotensin II receptor, glutamyl aminopeptidase, angiotensinogen, cathepsin A (CTSA), thimet oligopeptidase 1, neurolysin, alanyl aminopeptidase, cathepsin G, leucyl/cystinyl aminopeptidase (LNPEP), neprilysin, and carboxypeptidase A3 in the left atrium. The MR patients also had significantly upregulated expressions of MAS1 oncogene (MAS1) and mineralocorticoid receptor compared to normal controls. Additionally, in comparison with aortic valve disease patients, MR patients had significantly downregulated CTSA and LNPEP expression and significantly upregulated MAS1 expression in the left atrium. CONCLUSIONS: Expressions of genes in the renin-angiotensin system, especially CTSA, LNPEP, and MAS1, in the left atrium in MR patients significantly differed from expressions of these genes in aortic valve disease patients and normal controls. Notably, differences in expression were independent of circulating angiotensin II levels. The results of this study provide a rationale for pharmacological therapies or posttranslational regulation therapies targeting genes expressed differentially in the renin-angiotensin system to remedy structural remodeling associated with atrial enlargement and heart failure progression in patients with MR.

Successful repair of neonatal tricuspid regurgitation due to chordae rupture.

Neonatal rupture of the chordae of tricuspid valve with severe regurgitation is rare and disastrous. We report on a full-term female neonate presented with cyanosis caused by severe tricuspid regurgitation (TR) due to anterior leaflet chordal rupture. After initial stabilization by prostaglandin E1 infusion, successful early repair was achieved with artificial chordae implantation. The unique pathophysiology and the therapeutic strategy of this situation will be described.

Intramedullary reinforcement of sternal fixation with autologous xiphoid tenon.

Minimally invasive cardiac surgery through a partial sternotomy or a ministernotomy is popular. However, the transverse nonunion of the sternum will be a potential complication. Valid and valuable techniques have been introduced for securing the sternotomy fixation. Most of them are focused on the materials or methods for extrinsic reinforcement. A new concept, focused on the intramedullary reinforcement of the sternal fixation, was designed by incarcerating a cancellous portion of the autologous xiphoid in the marrow space of the inter-segmental junction of the partial sternotomy. This autologous xiphoid tenon method is simple, reliable, and reproducible without additional requirement of device implantation or an iliac incision for the bone grafting.

Long-term results of radiofrequency maze procedure for persistent atrial fibrillation with concomitant mitral surgery.

BACKGROUND: The radiofrequency (RF) maze procedure can effectively restore sinus rhythm in most patients with persistent atrial fibrillation (AF) and mitral disease. However, long-term results and predictors for late AF recurrence are still under investigation. METHODS: From December 1995 to November 2011, 207 consecutive patients with persistent AF and mitral disease underwent RF maze procedure and concomitant mitral surgery. The mean age was 54±12.4 year-old. Mitral surgery was performed in all patients and concomitant procedures including tricuspid surgery, aortic valve surgery, and atrial septal defect closure were carried on 164 patients. RESULTS: The in-hospital mortality was 3.9% (n=8) and late mortality was 8.2% (n=17). After a mean follow-up period of 101±50.9 months, 154 patients (74.4%) had long-term sinus conversion. A permanent pacer was implanted in 8 patients (3.9%). By Cox multivariate survival regression analysis, predictors for long-term sinus conversion were identified to be the duration of persistent AF, preoperative left atrial (LA) diameter, preoperative right atrial (RA) area, and preoperative beta-blocker use. The receiver operating characteristic (ROC) curve analysis showed that the best cutoff value for persistent AF duration, preoperative LA diameter, and preoperative RA area were 59.5 months, 59.85 mm, and 25.65 cm2. CONCLUSIONS: Longer persistent AF duration, larger preoperative LA diameter, larger preoperative RA area and preoperative beta-blocker use were the predictors for negative long-term outcome of RF maze procedure for the patients with persistent AF underwent concomitant mitral surgery. Timely referral of patients for surgery is mandatory.

Exploring Regulatory Mechanisms of Atrial Myocyte Hypertrophy of Mitral Regurgitation through Gene Expression Profiling Analysis: Role of NFAT in Cardiac Hypertrophy.

BACKGROUND: Left atrial enlargement in mitral regurgitation (MR) predicts a poor prognosis. The regulatory mechanisms of atrial myocyte hypertrophy of MR patients remain unknown. METHODS AND RESULTS: This study comprised 14 patients with MR, 7 patients with aortic valve disease (AVD), and 6 purchased samples from normal subjects (NC). We used microarrays, enrichment analysis and quantitative RT-PCR to study the gene expression profiles in the left atria. Microarray results showed that 112 genes were differentially up-regulated and 132 genes were differentially down-regulated in the left atria between MR patients and NC. Enrichment analysis of differentially expressed genes demonstrated that "NFAT in cardiac hypertrophy" pathway was not only one of the significant associated canonical pathways, but also the only one predicted with a non-zero score of 1.34 (i.e. activated) through Ingenuity Pathway Analysis molecule activity predictor. Ingenuity Pathway Analysis Global Molecular Network analysis exhibited that the highest score network also showed high association with cardiac related pathways and functions. Therefore, 5 NFAT associated genes (PPP3R1, PPP3CB, CAMK1, MEF2C, PLCE1) were studies for validation. The mRNA expressions of PPP3CB and MEF2C were significantly up-regulated, and CAMK1 and PPP3R1 were significantly down-regulated in MR patients compared to NC. Moreover, MR patients had significantly increased mRNA levels of PPP3CB, MEF2C and PLCE1 compared to AVD patients. The atrial myocyte size of MR patients significantly exceeded that of the AVD patients and NC. CONCLUSIONS: Differentially expressed genes in the "NFAT in cardiac hypertrophy" pathway may play a critical role in the atrial myocyte hypertrophy of MR patients.

Fontan Operation in a Patient with Severe Hypoplastic Right Pulmonary Artery, Single Ventricle, and Heterotaxy Syndrome.

Assessment of the pulmonary circulation status including pressure, resistance, size, and absence of anatomical distortion, is crucial to the successful Fontan operation. Most patients are found to have acceptable pulmonary arteries after previous palliation, although some degree of distortion is not uncommon. However, in rare instances, some patients have only one functioning lung with another pulmonary artery seriously hypoplastic or atretic. For theses patients, completion of a Fontan operation will be challenging. We reported a 17-year-old girl with a single ventricle and heterotaxy syndrome and only her left lung functioning, who underwent one-lung Fontan operation with a satisfactory result.

Circulating miR-148b-3p and miR-409-3p as biomarkers for heart failure in patients with mitral regurgitation.

BACKGROUND: MicroRNAs (miRs) regulate gene expression in heart failure. Circulating miRs as biomarkers for heart failure in mitral regurgitation patients (MR) remain unexplored. METHODS: This case-control study enrolled 32 MR patients with heart failure, 16 asymptomatic MR patients, and 12 control subjects without heart failure. We used next generation sequencing to study the gene expression profiles in the sera, and quantitative RT-PCR to study serum and tissue miRs in the left atria. RESULTS: Next generation sequencing analysis and enrichment analysis showed that 25 miRs were differentially expressed in the sera of MR patients with heart failure compared to control subjects. The circulating miR-148b-3p (p=0.002) and miR-409-3p (p=0.010) were significantly down-regulated in the MR patients with heart failure compared to control subjects. However, only circulation miR-148b-3p was significantly down-regulated in the MR patients without heart failure compared to control subjects (p=0.009). The tissue miR-409-3p was significantly down-regulated in the MR patients with heart failure compared to 3 purchased normal controls (p=0.041). Notably, the tissue RASGRP3 mRNA, target gene of miR-409-3p, was significantly up-regulated in the MR patients with heart failure compared to normal controls (p=0.010). The tissue FRY (p=0.010) and GADD45A (p=0.010) mRNAs, target genes of miR-148b-3p, were significantly up-regulated in the MR patients with heart failure compared to normal controls. CONCLUSIONS: Circulating miR-148b-3p might serve as biomarker for future development of heart failure and miR-409-3p might serve as biomarker for incident heart failure in MR patients.

Deciphering the gene expression profile of peroxisome proliferator-activated receptor signaling pathway in the left atria of patients with mitral regurgitation.

BACKGROUND: Differentially expressed genes in the left atria of mitral regurgitation (MR) pigs have been linked to peroxisome proliferator-activated receptor (PPAR) signaling pathway in the KEGG pathway. However, specific genes of the PPAR signaling pathway in the left atria of MR patients have never been explored. METHODS: This study enrolled 15 MR patients with heart failure, 7 patients with aortic valve disease and heart failure, and 6 normal controls. We used PCR assay (84 genes) for PPAR pathway and quantitative RT-PCR to study specific genes of the PPAR pathway in the left atria. RESULTS: Gene expression profiling analysis through PCR assay identified 23 genes to be differentially expressed in the left atria of MR patients compared to normal controls. The expressions of APOA1, ACADM, FABP3, ETFDH, ECH1, CPT1B, CPT2, SLC27A6, ACAA2, SMARCD3, SORBS1, EHHADH, SLC27A1, PPARGC1B, PPARA and CPT1A were significantly up-regulated, whereas the expression of PLTP was significantly down-regulated in the MR patients compared to normal controls. The expressions of HMGCS2, ACADM, FABP3, MLYCD, ECH1, ACAA2, EHHADH, CPT1A and PLTP were significantly up-regulated in the MR patients compared to patients with aortic valve disease. Notably, only ACADM, FABP3, ECH1, ACAA2, EHHADH, CPT1A and PLTP of the PPAR pathway were significantly differentially expressed in the MR patients compared to patients with aortic valve disease and normal controls. CONCLUSIONS: Differentially expressed genes of the PPAR pathway have been identified in the left atria of MR patients compared with patients with aortic valve disease and normal controls.

Early and intermediate-term results of the extracardiac conduit total cavopulmonary connection for functional single-ventricle hearts.

BACKGROUND/PURPOSE: Fontan operation has evolved from atriopulmonary connection to total cavopulmonary connection (TCPC) due to its advantages in terms of hemodynamics and reduction of atrium-related complications. We analyzed the early and intermediate-term results of extracardiac conduit TCPC (EC-TCPC) procedure in patients with functional single ventricle to investigate the risk factors of surgical mortality and intermediate failure. METHODS: Retrospective review of the medical records of 88 consecutive patients with functional single ventricle who underwent EC-TCPC from 2000 to 2013 was conducted. RESULTS: The follow-up was 100% complete, ranging from 3 months to 13 years (mean 7.0 ± 3.8 years). There were two (2.3%) hospital and 18 (20.4%) late deaths. The estimated event-free survival rates at 1 year, 5 years, and 10 years were 90.6%, 89.3%, and 77.2%, respectively. On univariate analysis, fenestration was the only risk factor for surgical mortality (p = 0.027). On multivariate analysis, the significant atrioventricular valve regurgitation was the only risk factor for intermediate failure (p = 0.017). CONCLUSION: The clinical results of EC-TCPC in patients with functional single ventricle were satisfactory. The patients who needed fenestration during operation had higher risk of surgical mortality. Significant atrioventricular valve regurgitation had negative impact on intermediate survival.

Thoracoscopic lobectomy for pulmonary vein occlusion after radiofrequency catheter ablation of atrial fibrillation.

BACKGROUND: Radiofrequency catheter ablation for paroxysmal atrial fibrillation is well established but not drawback free. Pulmonary vein stenosis is one of the complications and usually treated with stenting with the disadvantages of high re-stenosis rate and anticoagulant dependence. CASE PRESENTATION: Herein, we present the case of a 47 year-old lady, who suffered from fever and hemoptysis due to right inferior pulmonary vein occlusion after radiofrequency catheter ablation for paroxysmal atrial fibrillation. Eventually, thoracoscopic right lower lung lobectomy was inevitable with satisfactory result. CONCLUSIONS: Pulmonary vein stenosis is a major complication after radiofrequency ablation of atrial fibrillation. High suspicion and early detection in patients with pulmonary manifestations are mandatory for salvage the injured lung in early. If delayed, surgical resection of the involved lung, especially through the thoracoscopic approach will eradicate the problem with minimal complication.

The Prognostic Scoring System Establishment and Validation for Chronic Atrial Fibrillation Patients Receiving Modified Cox-Maze IV and Concomitant Cardiac Surgery.

OBJECTIVES: Traditional Cox maze III is the gold standard for treatment of atrial fibrillation (AF). Because of its invasiveness, it has been replaced by a simplified procedure involving radiofrequency ablation of modified Cox maze IV. Although the modified Cox maze IV has the advantages of simplicity and less morbidity, a lower rate of sinus rhythm conversion has been reported. We try to establish a scoring system to predict the outcome of this procedure. METHODS AND RESULTS: The derivation group consisted of 287 patients with structural heart disease and chronic AF who underwent cardiac surgery and modified Cox-maze IV procedure between August 2005 and March 2013. Demographics, clinical and laboratory variables were retrospectively collected as sinus conversional predictors. Overall sinus conversion rate was 75.8%. The parameters of the Soft Markers Scoring system included AF duration, preoperative left atrial (LA) size, rheumatic pathology and postoperative LA remodeling. We compared 80 patients from another hospital between January 2004 and December 2011 as a validation group to evaluate the power of the scoring system. Soft Markers Score indicated a good discriminative power by using the areas under the receiver operating characteristic curve (AUROC: 0.759 ± 0.032). The score was further divided into three groups: low (0-2), intermediate (3-5), and high (6-10), with predicted sinus conversion rates of 92.4%, 74.2%, and 47.8%, respectively. CONCLUSIONS: In patients with chronic AF receiving modified Cox-maze IV procedure, the Soft Markers Score demonstrated good discriminative power of predicting sinus recovery in our patients and applied well to the other validation populations.

Mitochondrial apoptotic pathway activation in the atria of heart failure patients due to mitral and tricuspid regurgitation.

Apoptosis occurs in atrial cardiomyocytes in mitral and tricuspid valve disease. The purpose of this study was to examine the respective roles of the mitochondrial and tumor necrosis factor-α receptor associated death domain (TRADD)-mediated death receptor pathways for apoptosis in the atrial cardiomyocytes of heart failure patients due to severe mitral and moderate-to-severe tricuspid regurgitation. This study comprised eighteen patients (7 patients with persistent atrial fibrillation and 11 in sinus rhythm). Atrial appendage tissues were obtained during surgery. Three purchased normal human left atrial tissues served as normal controls. Moderately-to-severely myolytic cardiomyocytes comprised 59.7±22.1% of the cardiomyocytes in the right atria and 52.4±12.9% of the cardiomyocytes in the left atria of mitral and tricuspid regurgitation patients with atrial fibrillation group and comprised 58.4±24.8% of the cardiomyocytes in the right atria of mitral and tricuspid regurgitation patients with sinus rhythm. In contrast, no myolysis was observed in the normal human adult left atrial tissue samples. Immunohistochemical analysis showed expression of cleaved caspase-9, an effector of the mitochondrial pathways, in the majority of right atrial cardiomyocytes (87.3±10.0%) of mitral and tricuspid regurgitation patients with sinus rhythm, and right atrial cardiomyocytes (90.6±31.4%) and left atrial cardiomyocytes (70.7±22.0%) of mitral and tricuspid regurgitation patients with atrial fibrillation. In contrast, only 5.7% of cardiomyocytes of the normal left atrial tissues showed strongly positive expression of cleaved caspase-9. Of note, none of the atrial cardiomyocytes in right atrial tissue in sinus rhythm and in the fibrillating right and left atria of mitral and tricuspid regurgitation patients, and in the normal human adult left atrial tissue samples showed cleaved caspase-8 expression, which is a downstream effector of TRADD of the death receptor pathway. Immunoblotting of atrial extracts showed that there was enhanced expression of cytosolic cytochrome c, an effector of the mitochondrial pathways, but no expression of membrane TRADD and cytosolic caspase-8 in the right atrial tissue of mitral and tricuspid regurgitation patients with sinus rhythm, and right atrial and left atrial tissues of mitral and tricuspid regurgitation patients with atrial fibrillation. Taken together, this study showed that mitochondrial pathway for apoptosis was activated in the right atria in sinus rhythm and in the left and right atria in atrial fibrillation of heart failure patients due to mitral and tricuspid regurgitation, and this mitochondrial pathway activation may contribute to atrial contractile dysfunction and enlargement in this clinical setting.

Enhanced expression of ROCK in left atrial myocytes of mitral regurgitation: a potential mechanism of myolysis.

BACKGROUND: Severe mitral regurgitation (MR) may cause myolysis in the left atrial myocytes. Myolysis may contribute to atrial enlargement. However, the relationship between Rho-associated kinase (ROCK) and myolysis in the left atrial myocytes of MR patients remain unclear. METHODS: This study comprised 22 patients with severe MR [12 with atrial fibrillation (AF) and ten in sinus rhythm]. Left atrial appendage tissues were obtained during surgery. Normal left atrial tissues were purchased. Immunofluorescence histochemical and immunoblotting studies were performed. RESULTS: The expression of ROCK2 in the myolytic left atrial myocytes of MR AF patients (p = 0.009) and MR sinus patients (p = 0.011) were significantly higher than that of the normal subjects. Similarly, the expression of ROCK1 in the myolytic left atrial myocytes of MR AF patients was significantly higher than that of the normal subjects (p = 0.010), and the expression of ROCK1 in the myolytic left atrial myocytes of MR sinus patients was higher than that of the normal subjects (p = 0.091). Immunofluorescence study revealed significant co-localization and juxtaposition of ROCK2 and cleaved caspase-3 in the left atrial myocytes both in the MR AF group (Pearson's coefficient = 0.74 ± 0.03) and the MR sinus group (Pearson's coefficient = 0.73 ± 0.02). Similarly, immunofluorescence study revealed significant co-localization and juxtaposition of ROCK1 and cleaved caspase-3 in the left atrial myocytes both in the MR AF group (Pearson's coefficient = 0.65 ± 0.03) and the MR sinus group (Pearson's coefficient = 0.65 ± 0.03). Correlation analysis demonstrated that there was a significant direct relationship between the expression of ROCK2 in the myolytic left atrial myocytes and left atrial diameter in the MR patients (p = 0.041; r = 0.440). Moreover, the ratio of phosphorylated myosin-binding subunit of myosin light chain phosphatase (pMBS)/total MBS of left atrial tissues was significantly higher in the MR AF group (p < 0.04) and the MR sinus group (p < 0.04) compared with the normal control group. CONCLUSIONS: The enhanced expression of ROCKs might be involved in the myolysis of the left atrial myocytes of MR patients.

Unraveling regulatory mechanisms of atrial remodeling of mitral regurgitation pigs by gene expression profiling analysis: role of type I angiotensin II receptor antagonist.

Left atrial enlargement associated with mitral regurgitation (MR) predicts a poor prognosis. However, the underlying regulatory mechanisms of atrial remodeling remain unclear. We used high-density oligonucleotide microarrays and enrichment analysis to identify the alteration of RNA expression pattern and biological processes involved in the atrial remodeling of pigs with and without MR. Gene arrays from left atria tissues were compared in 13 pigs (iatrogenic MR pigs [n = 6], iatrogenic MR pigs treated with valsartan [n = 4], and pigs without MR [n = 3]). A total of 22 genes were differentially upregulated by altered fold change >2.0 (Log2FC > 1), and 49 genes were differentially downregulated by altered fold change <0.5 (Log2FC < -1) in the left atria of the MR pigs compared with the pigs without MR. Enrichment analysis showed that renin-angiotensin system was identified in the Kyoto Encyclopedia of Genes and Genomes pathway. Notably, 12 of the 22 upregulated genes were identified to be downregulated by valsartan and 10 of the 49 downregulated genes were identified to be upregulated by valsartan. The tissue concentrations of angiotensin II and gene expression of hypertrophic gene, myosin regulatory light chain 2, ventricular isoforms, and fibrosis-related genes were significantly increased in the MR pigs compared with pigs without MR. In conclusion, differentially expressed transcriptome and related biological pathways have been identified in the left atria of the MR pigs compared with pigs without MR. Additionally, some of the differentially expressed genes could be regulated by type I angiotensin II receptor blocker.