Search

Objective The study objective was to determine whether mini-invasive transthoracoscopic atrial fibrillation ablation can delay the progression of atrial fibrillation from paroxysmal to persistent. Methods Patients aged 18 to 80 years with paroxysmal nonvalvular atrial fibrillation and a history of stroke or systemic thromboembolism were consecutively enrolled from September 2014 to June 2019. In the treatment group, patients underwent transthoracoscopic atrial fibrillation ablation plus left atrial appendage excision (atrial fibrillation ablation plus left atrial appendage excision group). Patients unwilling to receive surgical intervention were treated with antiarrhythmic drugs and oral anticoagulants and recruited as a control group (atrial fibrillation plus antiarrhythmic drugs group). The primary end point was the progression of atrial fibrillation from paroxysmal to persistent. Results This study included 49 patients in the atrial fibrillation plus antiarrhythmic drugs group (29 men) and 77 patients in the atrial fibrillation ablation plus left atrial appendage excision group (48 men). In the atrial fibrillation ablation plus left atrial appendage excision group, after a median follow-up of 951 days (interquartile range, 529-1366 days), 8 patients (10.4%) progressed to persistent atrial fibrillation. In the atrial fibrillation plus antiarrhythmic drugs group, after a median follow-up of 835 days (interquartile range, 548-1214 days), 14 patients (28.6%) progressed to persistent atrial fibrillation. The atrial fibrillation ablation plus left atrial appendage excision group had a significantly lower incidence of atrial fibrillation progression than the atrial fibrillation plus antiarrhythmic drugs group during follow-up (3.9 vs 12.3 per 100 person-years, log-rank 8.6, P = .003). Conclusions Patients with paroxysmal nonvalvular atrial fibrillation who chose to undergo transthoracoscopic atrial fibrillation ablation had a lower incidence of progression to persistent atrial fibrillation than patients who chose conservative therapy. This strategy might be especially suitable for patients with paroxysmal nonvalvular atrial fibrillation at high risk of stroke and high risk of bleeding.

Introduction: For those cardiac resynchronization therapy (CRT) candidates who experience left-ventricular (LV) lead placement failure or underwent concomitant cardiac surgeries, surgical placement of epicardial LV lead guided by electroanatomic mapping may be a promising alternative. Methods: Electroanatomic mapping was used to guide positioning of the LV lead through a surgical approach. The LV lead was placed at the region with the latest local LV activation and normal voltage, away from the scar. Results: From April 2010 to September 2018, 10 consecutive patients (3 female) underwent surgical epicardial LV lead implantation. Among them, 3 had other surgical indications simultaneously (including 1 CRT non-responder), and 7 had failed transvenous LV lead placement. After CRT, the QRS duration was shortened from 149.3 ± 20.4 ms to 125.1 ± 15.2 ms (p = 0.01). At 6 months, the LV ejection fraction was significantly improved and remained stable in the follow-up (FU) period thereafter (baseline vs. 6 months, 31.0 ± 8.3% vs. 42.2 ± 13.4%, p = 0.006). Other parameters, including the threshold and impedance of the LV lead, were also stable at a mean FU of 755 ± 406 days, and the NYHA functional classification decreased from 2.9 ± 0.7 to 1.8 ± 0.8 (p = 0.002). Conclusions: Placement of an epicardial LV lead guided by electroanatomic mapping could be used as an adjunctive strategy in patients who were unable or refractory to conventional CRT therapy. This approach could also be applied in patients who had other surgical indications at the same time.

Background: Cardiac hypertrophy is an important prepathology of, and will ultimately lead to, heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. This study aims to elucidate the effects and mechanisms of HINT1 (histidine triad nucleotide–binding protein 1) in cardiac hypertrophy and heart failure. Methods: HINT1 was downregulated in human hypertrophic heart samples compared with nonhypertrophic samples by mass spectrometry analysis. Hint1 knockout mice were challenged with transverse aortic constriction surgery. Cardiac-specific overexpression of HINT1 mice by intravenous injection of adeno-associated virus 9 (AAV9)–encoding Hint1 under the cTnT (cardiac troponin T) promoter were subjected to transverse aortic construction. Unbiased transcriptional analyses were used to identify the downstream targets of HINT1. AAV9 bearing shRNA against Hoxa5 (homeobox A5) was administrated to investigate whether the effects of HINT1 on cardiac hypertrophy were HOXA5-dependent. RNA sequencing analysis was performed to recapitulate possible changes in transcriptome profile.Coimmunoprecipitation assays and cellular fractionation analyses were conducted to examine the mechanism by which HINT1 regulates the expression of HOXA5. Results: The reduction of HINT1 expression was observed in the hearts of hypertrophic patients and pressure overloaded–induced hypertrophic mice, respectively. In Hint1 -deficient mice, cardiac hypertrophy deteriorated after transverse aortic construction. Conversely, cardiac-specific overexpression of HINT1 alleviated cardiac hypertrophy and dysfunction. Unbiased profiler polymerase chain reaction array showed HOXA5 is 1 target for HINT1, and the cardioprotective role of HINT1 was abolished by HOXA5 knockdown in vivo. Hoxa5 was identified to affect hypertrophy through the TGF-β (transforming growth factor β) signal pathway. Mechanically, HINT1 inhibited PKCβ1 (protein kinase C β type 1) membrane translocation and phosphorylation via direct interaction, attenuating the MEK/ERK/YY1 (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/yin yang 1) signal pathway, downregulating HOXA5 expression, and eventually attenuating cardiac hypertrophy. Conclusions: HINT1 protects against cardiac hypertrophy through suppressing HOXA5 expression. These findings indicate that HINT1 may be a potential target for therapeutic interventions in cardiac hypertrophy and heart failure.

Background A combination of endocardial and epicardial approaches has improved the overall success rate of ventricular tachycardia (VT) ablation in patients with cardiomyopathy. However, the origins of some VTs are truly intramural or close to coronary arteries, which makes this combined strategy either prone to failure or too risky. Objectives This observational study aimed to explore the feasibility and efficacy of direct epicardial ablation combined with intramural ethanol injection via surgical approach for inaccessible intramural VTs or VTs too close to coronary arteries. Methods In four canines ventricular lesions produced by direct epicardial injection of ethanol were assessed. Six consecutive patients with recurrent VT refractory to catheter endocardial and epicardial RF ablation and that remained inducible after surgical epicardial mapping and RF ablation were included. Ethanol was injected by needle at the epicardial RF ablation sites. The primary outcome was freedom of sustained VT determined by device interrogation and periodical 24h-holter recordings subsequently. Results In animal study, the lesions were homogenous and increased in size with the volume of ethanol injected. In all 6 patients ethanol injection at the target sites in the anterior or lateral left ventricle abolished inducible VT. Over a median follow-up of 22 months (range, 6~65), all patients remained free of sustained VT. One patient died of pulmonary infection one year after the procedure. Conclusions A hybrid strategy of surgical ablation combined with intramural ethanol injection is feasible and effective in patients with multiple failed percutaneous ablation attempts. This article is protected by copyright. All rights reserved.

Objective To examine the altitude differences in the optimal perfusate oxygenation (PpO2) in patients who underwent cardiac surgery. Methods We included children (aged 1 month to 18 years) with congenital heart diseases surgically repaired between 2012 and 2018. We included only patients who underwent cardiac surgery with arrested heart cardiopulmonary bypass. Primary outcome was severe systemic inflammatory response syndrome (SIRS). Logistic regression was used to evaluate the association between arterial PpO2 on continuous and categorical scales and severe SIRS by altitude. We established PpO2 thresholds that equated to a risk probability of roughly 0.185 or greater for developing severe SIRS in each group of altitude. Results Among 3918 patients from low altitudes and 2384 from high altitudes, high-altitude patients were older (median, 42.3 [interquartile range 22.8-75.8] vs 37.1 [17.7-69.1] months, P Conclusions This study suggests altitude differences in the association of arterial PpO2 with inflammatory response following pediatric cardiac surgery.

Little is known regarding precise estimates of the association between perfusate oxygenation (PpO2) and acute lung injury (ALI) following tetralogy of Fallot repair. The objective is to investigate PpO2 and the risk of ALI following tetralogy of Fallot repair in pediatric patients.We conducted a nested case-control study within a prospective Chinese TedaICH cohort including 134 ALI patients aged 1 month to 18 years undergoing complete repair of tetralogy of Fallot, and each was matched to two controls. We selected the highest PpO2 during aortic crossclamp as the exposure. Conditional logistic regression was used to quantify the association between PpO2 and overall ALI risk by covariates of interest. We identified and integrated the risk covariates to build ALI nomograms and internally validated the nomograms using bootstrapping.After adjusting for covariates, continuously and categorically higher PpO2 values were associated with ALI risk (all P 0.05), especially for those with a z-score of pulmonary annulus -4.0 (P = 0.002), McGoon ratio 1.5 (P = 0.029), and major aortopulmonary collateral arteries (P = 0.005), despite no statistical heterogeneity (all P interaction0.05). Younger age, lower oxyhemoglobin saturation, untreated minor aortopulmonary collateral arteries, transannular patch, larger transpulmonary gradient, major transfusion, and longer cardiopulmonary bypass time were independent risk factors for ALI (all P 0.05). Combining the PpO2 nomogram provided further risk discriminative information on ALI diagnosis compared with the covariate-based nomogram alone in the training cohort (AUC 0.865, 95% CI [0.828-0.903] vs. 0.869 [0.832-0.906], respectively) with no statistical significance (P = 0.445).The findings suggested an association between high PpO2 and ALI risk, and more importance should be attached to independent risk factors for ALI.

BACKGROUND Little is known regarding whether hyperoxic reoxygenation was associated with higher risk of cardiovascular disorder following tetralogy of Fallot repair. METHODS We performed a nested case-control study among patients aged 1 month-18 years undergoing complete repair of tetralogy of Fallot in 2012-2018. We measured the highest perfusate oxygenation (PpO2) during aortic occlusion in 107 cardiovascular disorder cases and in 321 controls matched 1:3 to the cases on date of surgery, sex, and area of residence. We analyzed the association between PpO2 and outcome using multivariable conditional logistic regression adjusted for covariates. We further identified and integrated the risk covariates to build prediction nomograms. RESULTS Cases had higher percentage of exposure to PpO2 > 200 mmHg (86.0% vs. 76.1%, p = .019) than controls. Patients with PpO2 > 200 mmHg had an increased risk of cardiovascular disorder compared to those with PpO2 ≤ 200 mmHg (odd ratio [OR] = 2.075, 95% confidence interval [CI] = 1.035, 4.158, p = .039) adjusted for matching, clinical and procedural covariates. Categorical PpO2, lower body mass index, lower SpO2, untreated minor aortopulmonary collateral arteries, high immediately postoperative central venous pressure, and longer cardiopulmonary bypass time were independent risk factors for cardiovascular disorder (all p

Background Little is known regarding the effect of cardiopulmonary bypass (CPB) reoxygenation on cardiac function following tetralogy of Fallot repair. We hypothesized that hyperoxic reoxygenation would be more strongly associated with myocardial dysfunction in children with tetralogy of Fallot. Methods We investigated the association of perfusate oxygenation (PpO2) associated with myocardial dysfunction among children aged 6–72 months who underwent complete repair of tetralogy of Fallot in 2012–2018. Patients were divided into two groups: lower PpO2 group (≤ 250 mmHg) and higher PpO2 (> 250 mmHg) group based on the highest value of PpO2 during aortic occlusion. The odd ratio (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression models. Results This study included 163 patients perfused with lower PpO2 and 213 with higher PpO2, with median age at surgery 23.3 (interquartile range [IQR] 12.5–39.4) months, 164 female (43.6%), and median body mass index 15.59 (IQR 14.3–16.9) kg/m2. After adjustment for baseline, clinical and procedural variables, patients with higher PpO2 were associated with higher risk of myocardial dysfunction than those with lower PpO2 (OR 1.770; 95% CI 1.040–3.012, P = 0.035). Higher PpO2, lower SpO2, lower pulmonary annular Z-score, and longer CPB time were independent risk factors for myocardial dysfunction. Conclusions Association exists between higher PpO2 and myocardial dysfunction risk in patients with tetralogy of Fallot, highlighting the modulation of reoxygenation during aortic occlusion to reduce cardiovascular damage following tetralogy of Fallot repair. Trial registration Clinical Trials. gov number NCT03568357. June 26, 2018

Background Porcine aortic valve (PAV) and bovine aortic valve (BAV) are commonly used in aortic valve replacement (AVR) surgeries. A detailed comparison for their hemodynamic and structural stress/strain performances would help to better understand valve cardiac function and select valve type and size for AVR outcome optimizations. Methods Eight fluid-structure interaction models were constructed to compare hemodynamic and stress/strain behaviors of PAV and BAV with 4 sizes (19, 21, 23, and 25 mm). Blood flow velocity, systolic cross-valve pressure gradient (SCVPG), geometric orifice area (GOA), flow shear stresses (FSS), and stress/strain were obtained for comparison. Results Compared with PAV, BAV has better hemodynamic performance, with lower maximum flow velocity (7.17%) and pressure (9.82%), smaller pressure gradient (mean and peak SCVPG: 8.92% and 9.28%), larger GOA (9.56%) and lower FSS (6.61%). The averages of the mean and peak net pressure gradient values from 4 BAV models were 8.10% and 8.35% lower than that from PAV models. Larger valve sizes for both PAV and BAV had improved hemodynamic performance. Maximum flow velocity, pressure, mean SCVPG and maximum FSS from 25 mm BAV were 36.80%, 15.81%, 39.05% and 38.83% lower than those from 19 mm BAV. The GOA of PAV and BAV 25 mm Valve were 43.75% and 33.07% larger than 19 mm valves, respectively. BAV has lower stress on the leaflets than PAV. Conclusions BAV had better hemodynamic performance and lower leaflets stress than PAV. More patient studies are needed to validate our findings.

BACKGROUND: Stand-alone minimally invasive radiofrequency (RF) ablation with left atrial (LA) appendectomy has been an effective surgical intervention for non-paroxysmal atrial fibrillation (AF) (NPAF) in patients with a medical history of thromboembolism for secondary stroke prevention. This study sought to assess the impact of this surgery on LA function. METHODS: A total of 37 NPAF patients with a medical history of stroke or thromboembolism were enrolled in this prospective observational study, all of whom underwent stand-alone minimally RF ablation with LA appendectomy. Echocardiography was used to evaluate LA function preoperatively and 1 week and 3 months postoperatively. All patients were divided into two groups (Group AF and Group SR) according to whether sinus rhythm (SR) was restored after the surgery. RESULTS: The surgery had no impact on LA function in Group AF. Once NPAF patients were restored to SR, LA minimal volume (LAV(min)) decreased immediately compared with pre-operation (22.98±13.76 vs. 17.68±9.52 mL; P

Chronic intermittent hypoxia (CIH) is key pathological mechanism of obstructive sleep apnea (OSA), which induced cardiac dysfunction. Filamin c (FLNC) is a muscle-restricted isoform and predominantly expressed in muscle tissue. In this study, we utilized a recently developed CIH rat model to mimic OSA, investigated the expression of FLNC in cardiomyocytes, and examined the correlations of FLNC with active caspase-3 to ascertain whether FLNC regulates the survival of cardiomyocytes. Forty Sprague-Dawley rats were randomly divided into normoxia and CIH groups. All rats were exposed either to normoxia or CIH 8 h daily for 6 weeks. Echocardiogram and HE staining were used to examine cardiac pathology, structure, and function. Body weight, heart weight, and blood gas values were recorded, respectively. The FLNC, Bax, Bcl-2, BNIP 3, and active caspase-3 proteins were detected by western blot; FLNC was examined by immunohistochemistry and immunofluorescence. Association of FLNC with cardiomyocyte apoptosis was detected by immunofluorescence. CIH induced cardiac injuries and caused arterial blood gas disorder. FLNC significantly increased in CIH-induced cardiomyocytes than that in normoxia tissues. Pro-apoptotic BNIP 3 and Bax proteins were significantly increased in CIH, whereas anti-apoptotic member Bcl-2 was decreased. Active caspase-3, a universal marker of apoptosis, was significantly increased in CIH group. Co-localizations of FLNC and active caspase-3 were observed in CIH group. These results suggested FLNC is implicated in the pathogenesis of CIH-induced cardiomyocyte apoptosis, and FLNC may serve as a novel cardioprotective target for OSA patients.

Background: Risk factors for healthcare associated infections (HAIs) following surgical repair of acute type A aortic dissection (TAAD) has not been well defined. Methods: This was a retrospective study of patients treated between Jan 2013 and May 2016 at the large tertiary teaching hospital in Jiangsu, China. Logistic regression analysis was performed to investigate the association patients with acute TAAD who underwent ascending aortic and arch replacement under deep hypothermic circulatory arrest (DHCA) and healthcare associated infections during hospitalization. Results: Of the final 210 patients with aortic dissection (AD) admitted to our hospital, 100 patients had TAAD (100/210, 47.62%), which were then allocated to the HAIs group (n=36) and Non-HAIs group (n=64). We found that DCHA >29 min [odds ratio (OR) =2.60, 95% confidential interval (CI), 1.01–6.80, P=0.048], preoperative PLT 9 /L (OR =3.62; 95% CI, 1.33–9.79; P=0.011) and D-dimer >4.25 mg/L (OR =2.83; 95% CI, 1.07–7.47; P=0.035) were independently associated with the occurrence of HAIs for the patients with TAAD following surgical repair. Hosmer-Lemeshow statistic of the model suggested perfect model discrimination from a perfect fit (χ 2 =4.77, P=0.6883). Logistic model was verified when the area under receiver operating characteristic (ROC) curve was equal to 0.7665. Conclusions: TAAD patients with longer DHCA time, lower preoperative PLT, higher serum D-dimer would significantly increase the risks after surgical repair of arch replacement.

Aims Unexplained scar-related atrial tachycardia (AT) has been frequently encountered in clinical practice. We hypothesized that idiopathic, isolated fibrotic atrial cardiomyopathy (ACM) underlies this rhythm disorder. This study was aimed to characterize the underlying substrate and to explore the aetiology of this unexplained scar-related AT. Methods and results Twenty-six (11 men, aged 46 ± 13 years) of 52 non-surgical scar-related AT patients identified by three-dimensional voltage mapping were enrolled in this prospective observational study. Multimodality image examinations (echocardiography, cardiac magnetic resonance, 99Tc single-photon emission computed tomography), ventricular voltage mapping, and intracardiac pressure curve recording ruled out ventricular involvement. Catheter ablation was acutely successful for all the patients, and pacemaker implantation was performed in seven patients who presented sinus node dysfunction or atrial standstill after termination of the AT. In three patients with multiple AT recurrences, the diseased areas of the right atrium were resected and dechannelled via mini-invasive surgical interventions. Histological examinations revealed profound fibrosis without amyloidosis or adipose deposition. Viral and familial investigations yielded negative results. Fibrosis progression over a median of 45 (5-109) months of follow-up manifested as atrial arrhythmia recurrence in seven patients and atrial lead non-capture due to newly developed atrial standstill in two patients. Two patients suffered four ischaemic stroke events before receiving anticoagulation treatment. Conclusion Isolated, fibrotic ACM may underlie the idiopathic scar-related ATs. This novel cardiomyopathy has unique clinical characteristics with high morbidity including stroke and warrants specific therapeutic strategies. Further investigations are required to determine the aetiology and mechanism.

Background We aimed to develop and validate a prediction model for in‐hospital complications in children with tetralogy of Fallot repaired at an older age. Methods and Results A total of 513 pediatric patients from the Tianjin data set formed a derivation cohort, and 158 pediatric patients from the Hefei and Xiamen data sets formed validation cohorts. We applied least absolute shrinkage and selection operator analysis for variable selection and logistic regression coefficients for risk scoring. We classified patients into different risk categorizations by threshold analysis and investigated the association with in‐hospital complications using logistic regression. In‐hospital complications were defined as death, need for extensive pharmacologic support (vasoactive‐inotrope score of ≥20), and need for mechanical circulatory support. We developed a nomogram based on risk classifier and independent baseline variables using a multivariable logistic model. Based on risk scores weighted by 11 preoperative and 4 intraoperative selected variables, we classified patients as low, intermediate, and high risk in the derivation cohort. With reference to the low‐risk group, the intermediate‐ and high‐risk groups conferred significantly higher in‐hospital complication risks (adjusted odds ratio: 2.721 [95% CI, 1.267–5.841], P =0.0102; 9.297 [95% CI, 4.601–18.786], P ARIAR ‐Risk classifier (absolute and relative low risk, intermediate risk, and aggressive and refractory high risk) with age and mean blood pressure showed good discrimination and goodness‐of‐fit for derivation (area under the receiver operating characteristic curve: 0.785 [95% CI , 0.731–0.839]; Hosmer‐Lemeshow test, P =0.544) and external validation (area under the receiver operating characteristic curve: 0.759 [95% CI , 0.636–0.881]; Hosmer‐Lemeshow test, P =0.508). Conclusions A risk‐classifier–oriented nomogram is a reliable prediction model for in‐hospital complications in children with tetralogy of Fallot repaired at an older age, and strengthens risk/benefit–based decision‐making.

Background Chronic intermittent hypoxia ( CIH ) is a distinct pathological mechanism of obstructive sleep apnea ( OSA ), which is recognized as an independent risk factor for cardiovascular diseases. The aims of this study were to ascertain whether CIH induces atrial fibrillation ( AF ), to determine whether cardiac sympathetic denervation ( CSD ) can prevent it and suppress blood pressure, and to explore the potential molecular mechanisms involved. Methods and Results Sixty Sprague‐Dawley male rats were randomly divided into 4 groups: sham, CSD , CIH , CIH + CSD . The rats were exposed either to CIH 8 hours daily or normoxia for 6 weeks. Cardiac pathology and structure were analyzed by hematoxylin and eosin staining and echocardiogram. ECG, blood pressure, body weight, and blood gas were recorded. Connexin 43 and tyrosine hydroxylase were detected by western blot, immunohistochemistry, and immunofluorescence. CIH induced atrial remodeling, and increased AF inducibility. CSD treatment reduced postapneic blood pressure rises and AF susceptibility, which could attenuate CIH ‐associated structural atrial arrhythmogenic remodeling. In addition, CIH ‐induced sympathetic nerve hyperinnervation and CSD treatment reduced sympathetic innervation, which may affect CIH ‐induced AF ‐associated sympathovagal imbalance. Connexin 43 was specifically downregulated in CIH , whereas CSD treatment increased its expression. Conclusions These results suggested CIH induces atrial remodeling, increases AF inducibility, results in sympathetic nerve hyperinnervation, and decreases connexin 43 expression, but CSD treatment reduces AF susceptibility, postapneic blood pressure increase, sympathetic innervation, and the alteration of Cx43, which may be a key point in the genesis of CIH ‐induced AF .

Concomitant occurrence of atrial myxoma and esophageal carcinoma is an extremely rare entity. Here we present two cases of synchronously suffered left atrial myxoma and esophageal carcinoma. Both patients underwent simultaneous resection of two tumors via the right thoraco-abdominal approach and recovered well.

Objectives: To identify risk factors associated with cardiac valve calcification that is easily detectable through routine blood tests in patients who received valve replacement therapy. Methods: Four hundred patients with valvular heart disease who underwent valve replacement surgery between December 2009 and January 2013 were enrolled in this study. Of these, 77 had valve calcification; the other 323 did not. Multivariate logistic regression analysis was used to assess for risk factors associated with valve calcification. Results: In our study population, rheumatic valve lesions were the most common reason for valve replacement. Degenerative nonstenotic valve lesion was a protective factor and degenerative stenotic valve lesion was a strong risk factor for valve calcification. Serum levels of gamma-glutamyl transferase (GGT) of between 30 and 46 IU/l and >90 IU/l and total bilirubin (TBIL) of between 15 and 20 μmol/l were positively correlated with valve calcification. Meanwhile, serum calcium (Ca2+) levels of between 2.3 and 2.4 mmol/l were negatively correlated with rheumatic valve calcification. Conclusions: Degenerative stenotic lesion is a risk factor and degenerative nonstenotic lesion a protective factor for cardiac valve calcification. Serum GGT and TBIL levels are positively correlated and serum Ca2+ levels negatively correlated with rheumatic cardiac valve calcification.

Aortic valve calcification develops in patients with chronic kidney disease who have calcium and phosphate metabolic disorders and poor prognoses. There is no effective treatment except valve replacement. However, metabolic disorders put patients at high risk for surgery. Increased acetylation of histones 3 and 4 is present in interstitial cells from human calcific aortic valves, but whether it is involved in aortic valve calcification has not been studied. In this study, we found that treating cultured porcine aortic valve interstitial cells with a high-calcium/high-phosphate medium induced calcium deposition, apoptosis, and expression of osteogenic marker genes, producing a phenotype resembling valve calcification in vivo. These phenotypic changes were attenuated by the histone acetyltransferase inhibitor C646. C646 treatment increased the levels of class I histone deacetylase members and decreased the acetylation of histones 3 and 4 induced by the high-calcium/high-phosphate treatment. Conversely, the histone deacetylase inhibitor suberoylanilide hydroxamic acid promoted valve interstitial cell calcification. In a mouse model of aortic valve calcification induced by adenine and vitamin D treatment, the levels of acetylated histones 3 and 4 were increased in the calcified aortic valves. Treatment of the models with C646 attenuated aortic valve calcification by restoring the levels of acetylated histones 3 and 4. These observations suggest that increased acetylation of histones 3 and 4 is part of the pathogenesis of aortic valve calcification associated with calcium and phosphate metabolic disorders. Targeting acetylated histones 3 and 4 may be a potential therapy for inoperable aortic valve calcification in chronic kidney disease patients., Cardiovascular disease: Averting a calcium catastrophe A therapeutic strategy for preventing calcium build-up in the heart could protect chronic kidney disease (CKD) patients from lethal cardiovascular complications. This accumulation is a common feature of late-stage CKD, resulting in obstruction of the aortic valve that can ultimately cause heart failure. A team led by Wei Sun and Xiangqing Kong of The First Affiliated Hospital of Nanjing Medical University in China has demonstrated that specific chemical modifications to histone proteins contribute to this process. Histones organize chromosomal DNA and can thereby regulate gene expression, and the researchers showed that a drug that inhibits histone-modifying acetyltransferase enzymes switches off biochemical pathways that promote calcium accumulation in cultured heart valve cells. They subsequently confirmed these protective effects in a mouse model of aortic valve calcification, indicating a potentially promising avenue for treating CKD.

Aims Aortic dissection (AD) represents one of the most common aortic emergencies with high incidence of morbidity and mortality. Clinical studies have shown that the increased excitability of the sympathetic nerve may be associated with the formation of AD. In this study, we examined the effects of bilateral superior cervical sympathectomy (SCGx) on the progression of β-aminopropionitrile (BAPN)-induced AD in rats. Main methods Sprague–Dawley rats were randomly divided into three groups, including BAPN, BAPN + SCGx and control groups. For terminal measurements, the mean arterial pressure (MAP) and heart rate (HR) were monitored and the basal sympathetic nerve activity (SNA) was assessed through recording the variation in arterial pressure in response to hexamethonium application. Pathological changes in the aortic wall were observed by histological staining. Matrix metalloproteinase-2 (MMP-2) and MMP-9 concentrations within the aortic wall were analyzed by western blot. Key findings The results show that BAPN administration could elevate SNA and cause the formation of AD in rats with a high incidence (67.7%), while SCGx treatment inhibited the elevation of SNA and significantly reduced the incidence (20%). SCGx may suppress the formation of BAPN-induced AD via restraining the rise of HR and reducing the MMP-9 concentration in aortic wall. Significance These results indicate that surgical techniques such as sympathetic nerve block may be a potentially useful therapy for the prevention of AD.

Background/Aims: To evaluate the long-term outcomes of Chinese patients with cardiac surgery-associated acute kidney injury (CSA-AKI). Methods: Patients who underwent cardiac surgery with a median 3-year follow-up were enrolled. The long-term survival rate and the incidence of chronic kidney disease (CKD) were recorded, and related risk factors were analyzed. Results: Of all 1,363 patients, 457 (33.5%) developed CSA-AKI. The AKI patients had a lower 3-year survival rate (88.8 vs. 97.2%, respectively, p < 0.001) and a higher incidence of CKD stages 3-5 (9.9 vs. 2.3%, respectively, p < 0.001) than the non-AKI patients. Cox regression analysis showed that AKI, atrial fibrillation, chronic cardiac insufficiency, longer surgical duration, respiratory failure after surgery, and longer mechanical ventilation time were associated with long-term mortality, while AKI, older age, and lower baseline kidney function were associated with incident CKD stages 3-5. Conclusion: CSA-AKI increased the risk of 3-year mortality and incident CKD stages 3-5.

Background Rheumatic heart disease is an autoimmune disease caused by group A streptococci infection and frequently affects the aortic valve. Sex differences are common in the disease progression, treatment, and outcome. However, little is known about the sex differences in the pathology of aortic valves in rheumatic heart disease. Design We studied the end-stage calcific aortic valves from male versus female patients to reveal the sex-dependent pathology differences and molecular changes associated with requiring valve replacement. Methods Aortic valves from 39 patients with rheumatic heart disease (19 males and 20 females) were collected at the time of aortic valve replacement for comparative pathology, immunohistochemistry, and gene expression analyses. Clinical characteristics were also analyzed and compared between the two groups. Results Aortic valves from female patients exhibited increased expression of collagens, infiltration of monocytes/macrophages and neovascularization. Aortic valves from female patients also had increased expression of inflammatory genes involved in the NFKB pathway (phosphorylated NFKB p65 subunit, IL8, and NOS3) and Th1 cytokine genes (IFNA and IL12B). The severe valve pathology in female patients was correlated with a higher serum level of anti-streptolysin O antibodies. Conclusion Inflammation is more prominent in aortic valves of female patients with rheumatic heart disease. This sex difference may contribute to the severe valve pathology and worse outcome of female patients.

Chronic heart failure (CHF) is responsible for significant morbidity and mortality worldwide, mainly as a result of neurohumoral activation. Acupuncture has been used to treat a wide range of diseases and conditions. In this study, we investigated the effects of electroacupuncture (EA) on the sympathetic nerve activity, heart function, and remodeling in CHF rats after ligation of the left anterior descending coronary artery. CHF rats were randomly selected to EA and control groups for acute and chronic experiments. In the acute experiment, both the renal sympathetic nerve activity and cardiac sympathetic afferent reflex elicited by epicardial application of capsaicin were recorded. In the chronic experiment, we performed EA for 30 min once a day for 1 wk to test the long-term EA effects on heart function, remodeling, as well as infarct size in CHF rats. The results show EA significantly decreased the renal sympathetic nerve activity effectively, inhibited cardiac sympathetic afferent reflex, and lowered the blood pressure of CHF rats. Treating CHF rats with EA for 1 wk dramatically increased left ventricular ejection fraction and left ventricular fraction shortening, reversed the enlargement of left ventricular end-systolic dimension and left ventricular end-diastolic dimension, and shrunk the infarct size. In this experiment, we demonstrated EA attenuates sympathetic overactivity. Additionally, long-term EA improves cardiac function and remodeling and reduces infarct size in CHF rats. EA is a novel and potentially useful therapy for treating CHF.

Background and purpose Periostin, a matricellular protein, plays an important role in cardiac development and remodeling. Its expression profile and the association with myocardial fibrosis have not been investigated in human failing hearts. This work aimed to explore the behavior and pathologic significance of periostin in signifying collagen fibrogenesis in human hearts from patients with end-stage heart failure. Methods and subjects Tissues were collected from heart transplant recipients and the control hearts were from unmatched donors. Periostin mRNA and protein were detected using quantitative real-time polymerase chain reaction and Western blotting. Immunohistochemistry staining was employed to directly detect the protein level and distribution of periostin in heart tissues. The extent of myocardial fibrosis was expressed by the percentage of Masson's trichrome staining. Gelatin zymography was used to detect the activities of matrix metalloproteinase (MMP)2 and MMP9. Results A low level of periostin mRNA expression was found in control hearts while not detectable at the protein level. Periostin mRNA was increased significantly in failing myocardium compared to that of controls. Periostin was distributed extensively in left ventricle and interventricular septum of the failing hearts. Correlation analysis showed periostin protein expression was positively associated with myocardial fibrosis as well as left ventricular diastolic dimension. The distribution and extent of periostin was consistent with that of myocardial fibrosis. MMP2 activity has an obvious increase about fourfold in heart tissues from HF patients. But there is no quantitative association with the expression of periostin. Conclusions Periostin, the distribution and expression of which were consistent with the extent of myocardial fibrosis, might be a potential biomarker of cardiac remodeling in heart failure patients.

ABSTRACT: Aims: To examine the relationship between the expression levels of miR-1 and PIK3CA in resected non-small-cell lung cancer (NSCLC) tissues and clinical characteristics and prognosis. Materials & methods: Levels of miR-1 and PIK3CA in cancerous and normal tissues obtained from 55 patients with NSCLC were measured by real-time PCR and western blot assays, and their associations with clinicopathological features were evaluated. Results: A total of 69.1% of the NSCLC tissue samples showed low miR-1 expression (p < 0.05) and 70.9% showed high PIK3CA expression (p < 0.05). Patients with low miR-1 expression and those with high PIK3CA expression had significantly higher incidences of lymph node metastases and postoperative recurrences within 1 year after surgery than those with moderate miR-1 expression and moderate PIK3CA expression (p < 0.05 for both). Conclusion: Low expression of miR-1 and overexpression of PIK3CA in NSCLC tissues may be useful predictors of lymph node metastasis and postoperative recurrence in patients with NSCLC.

Background Despite the successful creation of complex lesion sets during hybrid ablation (HA), reoccurrence of atrial fibrillation (AF), and/or atrial arrhythmia and procedural complications still occur. The main objective of this study was to compare the efficacy and safety between HA and transcatheter ablation (TA). Methods We searched Pubmed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) database up to October 2017. Studies that satisfied our predefined inclusion criteria were included. Of the 894 records, 4 studies encompassing 331 patients were included in our study. We assessed pooled data using random-effect or fixed-effect model. The main endpoint was freedom of atrial arrhythmia after follow-up duration, secondary results were procedure time and intraoperative and postoperative adverse events. Similarly, tertiary outcomes were endocardial time, fluoroscopy time, and postoperative hospitalization. Results Compared with TA, HA treatment through mini-thoracotomy access improved superiority in freedom of atrial arrhythmia after follow-up duration (odds ratio [OR] = 6.67, 95% confidence interval [CI]: 2.63-16.90), but HA increased the incidence of intraoperative and postoperative adverse events for AF patients (OR = 2.98, 95% CI: 1.30-6.83). HA through either mini-thoracotomy or transdiaphragmatic/subxiphoid access had longer procedure time and postoperative hospitalization than TA. However, endocardial time was shorter than TA. Conclusions For AF patients, HA possessed of an overall superior outcome using mini-thoracotomy way to TA. Although HA had longer procedure time, it yielded a reduction in endocardial time. Meanwhile, we should pay attention to the significantly high risk of intraoperative and postoperative adverse events that the HA generated.

Objectives The aim of this study was to determine whether altered calreticulin expression and distribution contribute to the pathogenesis of atrial fibrillation (AF) associated with valvular heart disease (VHD). Background AF affects electrophysiological and structural changes that exacerbate AF. Atrial remodeling reportedly underlies AF generation, but the precise mechanism of atrial remodeling in AF remains unclear. Methods Right and left atrial specimens were obtained from 68 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (SR; n =25), paroxysmal AF (PaAF; n =11), and persistent AF (PeAF; AF lasting >6months; n =32) groups. Calreticulin, integrin-α5, and transforming growth factor-β1 (TGF-β1) mRNA and protein expression were measured. We also performed immunoprecipitation for calreticulin with either calcineurin B or integrin-α5. Results Calreticulin, integrin-α5, and TGF-β1 mRNA and protein expression were increased in the AF groups, especially in the left atrium in patients with mitral valve disease. Calreticulin interacted with both calcineurin B and integrin-α5. Integrin-α5 expression correlated with TGF-β1 expression, while calreticulin expression correlated with integrin-α5 and TGF-β1 expression. Despite similar cardiac function classifications, calreticulin expression was greater in the PeAF group than in the SR group. Conclusions Calreticulin, integrin-α5, and TGF-β1 expression was increased in atrial tissue in patients with AF and was related to AF type, suggesting that calreticulin is involved in the pathogenesis of AF in VHD patients.

Amplification and overexpression of human epidermal growth factor receptor-2 (HER-2) has been shown in subgroups of gastric cancer, correlated to more aggressive disease and predictive for the treatment with HER-2 antibodies. In this study, we examined the prognostic value of HER-2 expression in primary gastric cancer and in associated lymph node metastases and confirmed the role of HER-2 in tumor angiogenesis by examining vascular endothelial growth factor (VEGF) expression.Immunohistochemistry was used to detect HER-2 and VEGF expression in 110 gastric cancer specimens and associated lymph node metastases and in 96 specimens of normal gastric mucosa.The expression level of HER-2 in gastric tissues was significantly higher than in normal tissues (19.1 % vs. 8.3 %; P0.05). HER-2 overexpression was homogeneous in primary gastric cancer and metastatic lymph nodes (P = 0.607). There was a significant positive correlation of HER-2 expression and VEGF expression (P = 0.007). HER-2 overexpression in primary tumor correlated with lymph node metastasis, distant metastasis, and American Joint Committee on Cancer (AJCC) stage. Cox regression multivariate analyses confirmed that tumor size, histological grade, lymph node ratio, AJCC stage, chemotherapy, and HER-2 expression were all prognostic factors. Patients with HER-2 positivity in both primary and metastatic tissues (+/+) had the poorest survival (OS, 12.5 months; DFS, 11.0 months) (P0.01).HER-2 was significantly overexpressed in gastric cancer versus normal tissue and correlated with VEGF expression. HER-2 in tumor or lymph nodes was an independent negative prognostic factor.

Platinum-based chemotherapy is the most common treatment for patients with advanced non-small cell lung cancer (NSCLC). Genetic polymorphisms in the base excision repair (BER) pathway are suspected to influence the response of patients to this type of therapy. In this study, we investigated whether nonsynonymous single nucleotide polymorphisms (SNPs) in the BER pathway were associated with the response, progression-free survival (PFS) and overall survival (OS) of NSCLC patients following platinum-based chemotherapy. We used TaqMan to genotype four SNPs (APE1 Asp148Glu, PARP1 Va1762Ala, XRCC1 Arg194Trp and XRCC1 Arg399Gln) in 147 patients with advanced NSCLC who had undergone routine platinum-based chemotherapy. Logistic regression analysis showed that subjects with the XRCC1-399 A allele had a significantly better response to platinum-based chemotherapy than those with the XRCC1-399 GG genotype (AA/AG vs. GG: adjusted OR = 2.35, 95 % CI = 1.11–5.00). Furthermore, multivariate Cox proportional hazard regression analysis showed that the PARP1-762 CC genotype was a significantly unfavorable prognostic factor for PFS (CC vs. CT/TT: adjusted HR = 1.90, 95 % CI = 1.02–3.52). In contrast, the APE1-148 GG genotype was a significantly protective prognostic factor for OS (GG vs. TT: adjusted HR = 0.33, 95 % CI = 0.12–0.92). We found that XRCC1 Arg399Gln, PARP1 Va1762Ala and APE1 Asp148Glu SNPs in the BER pathway may influence the prognosis of advanced NSCLC patients following platinum-based chemotherapy.

There is controversy regarding the impact of different depths of submucosal invasion on lymph node metastasis (LNM) and overall survival (OS). We evaluated the impact of depth of submucosal invasion on the presence of metastatic lymphadenopathy and survival in a Chinese population with esophageal squamous cell carcinoma (ESCC).A total of 258 patients who underwent esophagectomy from November 2009 to March 2014 were studied. Demographics of patients, tumor characteristics, and surgical information were retrospectively collected through medical records. Submucosal invasion was equally categorized into inner one-third (sm1), middle one-third (sm2), and deep one-third (sm3) invasion by pathologists. The patients were observed at the outpatient department in accordance with appointed time and recurrence, and deaths were recorded. The median follow-up duration was 26 months and the deadline was April 2015. Cancer characteristics and its association with LNM and OS were analyzed.The study included 75 (29.1%) sm1, 73 (28.3%) sm2, and 110 (42.6%) sm3 patients, and the rates of LNM were 12% (9/75), 11% (8/73), and 20.9% (23/110), respectively. sm3 might be associated with regional LNM (univariate analysis, P=0.041). Tumor volume1.856 cm(3) (P=0.022) and lymphovascular invasion (LVI) (P=0.004) predicted LNM using multivariate analysis. No significant differences in distant metastases were observed according to the depth of invasion. Only metastatic lymph nodes predicted OS (P0.001) rather than the depth of invasion.Submucosal ESCC showed a substantial rate of LNM. In T1b ESCC, after adjusting for possible covariates, depth of invasion does not predict LNM or OS.

The human epidermal growth factor receptor 2 (HER-2) and leptin/OB-R system have been reported to be intertwined in several cancer types. However, limited research has been conducted with regard to this interaction in lung cancers. In this study, we investigated the relationship between the expression levels of these proteins and the development, progression and prognosis of non-small-cell lung cancer (NSCLC). The expression of leptin, OB-Rb and HER-2 was evaluated in 100 NSCLC specimens by immunohistochemistry, with normal lung tissue as controls. The relationships between their expression levels and clinicopathological factors were evaluated by correlation analysis. Univariate and multivariate analyses were used to determine the associations between the expression levels of these proteins and the survival of NSCLC patients. Leptin was expressed in 71 and 25% (P

Hydrogen sulfide (H2S) is a gasotransmitter which regulates multiple cardiovascular functions. However, the precise roles of H2S in modulating myocardial fibrosisin vivoand cardiac fibroblast proliferationin vitroremain unclear. We investigated the effect of GYY4137, a slow-releasing H2S donor, on myocardial fibrosis. Spontaneously hypertensive rats (SHR) were administrated with GYY4137 by intraperitoneal injection daily for 4 weeks. GYY4137 decreased systolic blood pressure and inhibited myocardial fibrosis in SHR as evidenced by improved cardiac collagen volume fraction (CVF) in the left ventricle (LV), ratio of perivascular collagen area (PVCA) to lumen area (LA) in perivascular regions, reduced hydroxyproline concentration, collagen I and III mRNA expression, and cross-linked collagen. GYY4137 also inhibited angiotensin II- (Ang II-) induced neonatal rat cardiac fibroblast proliferation, reduced the number of fibroblasts in S phase, decreased collagen I and III mRNA expression and protein synthesis, attenuated oxidative stress, and suppressedα-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) expression as well as Smad2 phosphorylation. These results indicate that GYY4137 improves myocardial fibrosis perhaps by a mechanism involving inhibition of oxidative stress, blockade of the TGF-β1/Smad2 signaling pathway, and decrease inα-SMA expression in cardiac fibroblasts.

Background Most postsurgical macroreentry atrial tachycardias (PS-MATs) are atriotomy related; however, underlying mechanisms and prevention remain undefined. Objective The purpose of the present study was to investigate the electrophysiological and histologic bases of right atriotomy incision arrhythmogenicity and whether a modified atriotomy that extends the incisional line to the tricuspid annulus (TA) and inferior vena cava (IVC) prevents PS-MAT. Methods Atrial arrhythmia induction and electrophysiological and histologic characteristics were studied 8 weeks after right atriotomy in 30 adult swine according to incision distance to TA or IVC (groups A, B, and C: broad, narrow, and closed corridors, respectively; group D, no-incision sham; n=6 per group, except n=12 for group B). Results Sustained PS-MATs were induced and mapped in the broad- and narrow-corridor groups (A, 1 of 6 [16.7%] vs B, 5 of 12 [41.7%]) but not in the closed-corridor (C) or sham (D) groups ( P = .087). With 20-ms pacing cycle–length decrements (from 350 to 270 ms), mean conduction time over 20 mm at the atriotomy-to-TA corridor was 29.2 ± 2.2, 31.0 ± 4.2, 26.0 ± 1.9, and 17.0 ± 1.4 ms for 5 and 10 mm (both group B), 15 mm (group A), and sham incision ( P = .017), respectively. Conduction properties correlated with histologic findings: the wider the corridor, the healthier its tissue. In group C (modified atriotomy), both corridors were replaced by dense scar with complete conduction block. Conclusion Atriotomy corridor width determines conduction properties and contributes to arrhythmogenicity. A modified right atriotomy that extends to the TA and IVC prevents PS-MAT.

Background We tested the hypothesis that direct renin inhibition with aliskiren protects against myocardial ischemia/reperfusion (I/R) injury in spontaneously hypertensive rats ( SHR ), and examined the mechanism by which this occurs. Methods and Results Male SHR were treated (orally, 4 weeks) with saline or aliskiren (30 or 60 mg kg −1 day −1 ) and subjected to 30 minutes of left anterior descending coronary artery occlusion followed by 6 or 24 hours of reperfusion. Only the higher dose significantly lowered systolic blood pressure, the lower dose causing a smaller apparent lowering that was nonsignificant. Despite this difference in blood pressure‐lowering effect, both doses increased the ejection fraction and fractional shortening and reduced myocardial infarct size equally. I/R decreased cardiac expression of phosphatidylinositol 3‐kinase (PI3K), phospho‐Akt and phospho‐endothelial nitric oxide synthase (phospho‐ eNOS ), but increased expression of inducible nitric oxide synthase ( iNOS ); these changes were all abrogated by aliskiren. Moreover, aliskiren decreased superoxide anion generation and increased cyclic guanosine‐3′,5′‐monophosphate, an index of bioactive nitric oxide, in myocardium. It also decreased the expression of myocardial matrix metalloproteinase‐2, matrix metalloproteinase‐9, and tissue inhibitor of metalloproteinases‐1 ( TIMP ‐1) following I/R. In a L angendorff heart preparation, the detrimental cardiac effects of I/R were abrogated by aliskiren, and these protective effects were abolished by NOS or PI3K inhibition. In a parallel study, although specific iNOS inhibition reduced plasma malondialdehyde and myocardial superoxide anion generation, it did not affect the deleterious effects of I/R on myocardial structure and function. Conclusions Direct renin inhibition protects against myocardial I/R injury through activation of the PI3K‐Akt‐ eNOS pathway.

Background Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK) inhibitor of epidermal growth factor receptor (EGFR), displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC) in Chinese population are not sufficient. Purpose To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC), a study of single agent treatment with gefitinib in Chinese patients was conducted. Methods 45 patients with advanced NSCLC were treated with gefitinib (250 mg daily) until the disease progression or intolerable toxicity. Results Among the 45 patients, 15 patients achieved partial response (PR), 17 patients experienced stable disease (SD), and 13 patients developed progression disease (PD). None of the patients achieved complete response (CR). The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively). The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively). In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively). Conclusions Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. Unfortunately, the precise mechanisms and sensitive serum biomarkers of atrial remodeling in AF remain unclear. The aim of this study was to determine whether the expression of the transcription factors NF-AT3 and NF-AT4 correlate with atrial structural remodeling of atrial fibrillation and serum markers for collagen I and III synthesis. Methods Right and left atrial specimens were obtained from 90 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (n = 30), paroxysmal atrial fibrillation (n = 30), and persistent atrial fibrillation (n = 30) groups. NF-AT3, NF-AT4, and collagen I and III mRNA and protein expression in atria were measured. We also tested the levels of the carboxyl-terminal peptide from pro-collagen I, the N-terminal type I procollagen propeptides, the N-terminal type III procollagen propeptides, and TGF-β1 in serum using an enzyme immunosorbent assay. Results NF-AT3 and NF-AT4 mRNA and protein expression were increased in the AF groups, especially in the left atrium. NF-AT3 and NF-AT4 expression in the right atrium was increased in the persistent atrial fibrillation group compared the sinus rhythm group with similar valvular disease. In patients with AF, the expression levels of nuclear NF-AT3 and NF-AT4 correlated with those of collagens I and III in the atria and with PICP and TGF-β1 in blood. Conclusions These data support the hypothesis that nuclear NF-AT3 and NF-AT4 participates in atrial structural remodeling, and that PICP and TGF-β1 levels may be sensitive serum biomarkers to estimate atrial structural remodeling with atrial fibrillation.