DNMT1-induced miR-133b suppression via methylation promotes myocardial fibrosis after myocardial infarction.

Myocardial fibrosis is an underlying cause of many cardiovascular diseases. Novel insights into the epigenetic control of myocardial fibrosis are now emerging. The current work is focused on investigating the biological role of DNA methyltransferase 1 (DNMT1) in myocardial fibrosis as well as the underlying mechanism. Our findings revealed that DNMT1 expression levels were upregulated, whereas miR-133b expression levels were decreased in a rat model of myocardial fibrosis following myocardial infarction. In vitro, the expression levels of DNMT1 increased and those of miR-133b decreased after Ang-II treatment in cardiac fibroblasts. DNMT1 knockdown inhibited Ang-II-induced cardiac myofibroblast activation, and DNMT1 overexpression increased the proliferation and collagen generation of cardiac myofibroblasts. Furthermore, DNMT1 expression levels decreased, while miR-133b expression levels increased after treatment with 5-Aza (5-Azacytidine, a known inhibitor of DNA methylation) in Ang-II-induced cardiac fibroblasts. BSP (Bisulfite sequencing PCR) results showed a marked decrease in methylation levels in the miR-133b promoter region upon overexpression of DNMT1, whereas knockdown of DNMT1 blocked increased methylation levels in the miR-133b promoter region in Ang-II-induced cardiac fibroblasts. Finally, 5-Aza treatment reduced the progression of myocardial fibrosis after myocardial infarction in rats in vivo. Collectively, our results suggest that DNMT1 mediates CTGF expression in cardiac fibroblast activation by regulating the methylation of miR-133b. The present work reveals the unique role of the DNMT1/miR-133b/CTGF axis in myocardial fibrosis, thus suggesting its great therapeutic potential in the treatment of cardiac diseases.

The relationship between C-reactive protein to lymphocyte ratio and the prevalence of myocardial infarction in US adults: A cross-sectional study.

Objective: C-reactive protein to lymphocyte ratio (CLR) has been identified as a novel inflammatory biomarker. However, the role of CLR in myocardial infarction is unclear. Thus, this study designs to investigate the association of CLR with the prevalence of myocardial infarction in a large multiracial population in the United States. Methods: Participants from the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020 Pre-pandemic were included in this cross-sectional study. Multivariable regression and subgroup analyses, controlling for demographic variables, were performed to examine the association between CLR and its quintiles and myocardial infarction. A smooth curve fitting was used to model the non-linear relationship between them. Results: A total of 12,615 participants aged ≥18 years were recruited, of whom 609 (4.83%) self-reported a history of myocardial infarction. Compared to those in the lowest quartile of ln-transformed CLR (Q1), the myocardial infarction risks for subjects in Q2, Q3, and Q4 were 1.64, 1.71, and 1.79 times, respectively. Obvious upward trends were observed when ln-transformed CLR increased (P for trend <0.01). In continuous analyses, the fully adjusted odds ratios (OR) for myocardial infarction prevalence per ln-transformed increment in CLR was 1.46 (95% CI: 1.16-1.84, P < 0.01). Furthermore, a linear association was detected for ln-transformed CLR with the risk of myocardial infarction. Interaction test showed that the effect of CLR on myocardial infarction was significantly affected by age (P for interaction = 0.04). Conclusions: Data from a large, cross-sectional cohort program show that CLR is positively associated with myocardial infarction prevalence. Our findings highlight that CLR may be a novel inflammation warning biomarker for myocardial infarction.

Eccentricity-paced geomagnetic field and monsoon rainfall variations over the last 870 kyr.

Whether there are links between geomagnetic field and Earth's orbital parameters remains unclear. Synchronous reconstructions of parallel long-term quantitative geomagnetic field and climate change records are rare. Here, we present 10Be-derived changes of both geomagnetic field and Asian monsoon (AM) rainfall over the last 870 kyr from the Xifeng loess-paleosol sequence on the central Chinese Loess Plateau. The 10BeGM flux (a proxy for geomagnetic field-induced 10Be production rate) reveals 13 consecutive geomagnetic excursions in the Brunhes chron, which are synchronized with the global records, providing key time markers for Chinese loess-paleosol sequences. The 10Be-derived rainfall exhibits distinct ~100 kyr glacial-interglacial cycles, and superimposed precessional (~23 kyr) cycles that match with those in Chinese speleothem δ18O record. We find that changes in the geomagnetic field and AM rainfall share a common ~100 kyr cyclicity, implying a likely eccentricity modulation of both the geomagnetic field and climate.

Relieving Compression-Induced Local Wear on Non-Volatile Memory Block via Sliding Writes.

Due to its non-volatility and large capacity, NVM devices gradually take place at various levels of memories. However, their limited endurance is still a big concern for large-scale data centres. Compression algorithms have been used to save NVM space and enhance the efficiency of those lifetime extension methods. However, their own influence on the NVM lifetime is not clear. In order to fully investigate the impact of compression on NVM, this paper first studies bit flips involved in several typical compression algorithms. It is found that more bit flips would happen in the shrunken area of a memory block. This induces the phenomenon of intra-block wear unevenness, which sacrifices NVM lifetime. We propose a new metric called local bit flips to describe this phenomenon. In order to relieve the intra-block wear unevenness caused by compression, this paper proposes a sliding write method named SlidW to distribute the compressed data across the whole memory block. We first divide the memory block into several areas, and then consider five cases about the relationship between new data size and left space. Then, we place the new data according to the case. Comprehensive experimental results show that SlidW can efficiently balance wear and enhance NVM lifetime.

Application of Transesophageal Echocardiography in Amplatzer Atrial Septal Defect Occluder for Percutaneous Closure of Large Patent Foramen Ovale.

Objective: The Amplatzer patent foramen ovale (PFO) occluder is the most commonly used device for percutaneous closure of a large PFO. However, its use may predispose the patient to postoperative residual shunting. To reduce the incidence of residual shunting, we investigated the safety and effectiveness of the Amplatzer atrial septal defect (ASD) occluder for percutaneous closure of a large PFO measured by transesophageal echocardiography (TEE) and evaluated the value of TEE in this procedure. Methods: Overall, 118 patients who were diagnosed with a large PFO (all with a ≥ 2 mm left atrial side height after the Valsalva maneuver (VM) excluding those with a small ASD) using contrast transthoracic echocardiography (c-TTE) and TEE underwent closure under TEE guidance at The First Affiliated Hospital of Xi'an Jiaotong University. An ASD device was used in 48 patients (group I) and a PFO device in 70 (group II). After the procedure, we verified the safety and efficacy of different devices using c-TTE, TTE, and TEE. Results: In both groups, the preoperative TEE results showed a significantly increased left height of the PFO after VM compared with that at rest (all P < 0.01). Compared with the left height of the PFO measured using TEE after VM, the PFO-stretch diameter (SD) measured by TEE after the delivery sheath passed the PFO was higher (all P < 0.01). We selected the ASD occluder size according to this PFO-SD. In group II, most patients underwent the implantation of the larger PFO devices. Interventional treatment was successfully performed on all patients. The effective occlusion rate in group I at 12 months after the procedure was significantly higher than that in group II (93.7% vs. 78.6%, P < 0.05). The TEE results showed that 18 patients with a medium and large residual shunt at 12 months after the procedure exhibited an intradisc tunnel-like shunt. Conclusion: The Amplatzer ASD device and Amplatzer PFO device are safe for large PFO closure, but the Amplatzer ASD device has a higher effective occlusion rate. TEE plays a crucial role in the use of the Amplatzer ASD occluder for percutaneous closure of a large PFO.

Transjugular Approach to Closure of Patent Foramen Ovale Under the Guidance of Fluoroscopy and Transthoracic Echocardiography: A Case Report.

Background: We describe a rare case of patent foramen ovale (PFO) associated stroke in a patient with pulmonary embolism, inferior vena cava thrombosis and undergoing filter implantation who successfully underwent PFO closure using the right internal jugular venous approach. Case Summary: This is a rare case of a 42-year-old patient who presented with stroke and pulmonary embolism and was diagnosed with a PFO, inferior vena cava thrombosis and underwent filter implantation. The patient suffered from stroke and pulmonary embolism successively; that is, embolic events occurred in both the arterial and venous systems. Transesophageal echocardiography (TEE) showed a PFO with an atrial septal aneurysm (ASA), which we considered a "pathological" PFO. Due to the obstructive nature of the inferior vena cava approach, we successfully performed PFO closure via the right internal jugular venous approach under the guidance of X-ray and transthoracic echocardiography (TTE). Discussion: The right jugular venous approach provides a simple technical solution for patients who require PFO closure when femoral venous access is unavailable, which can be performed under X-ray and TTE guidance.

Efficacy and Safety of Left Atrial Appendage Occlusion in Mild Mitral Stenosis Patients with High Bleeding Risk.

Atrial fibrillation (AF) is highly prevalent in patients with mitral stenosis (MS), but the efficacy of left atrial appendage occlusion (LAAO) in these patients remains unclear.The aim of this study was to evaluate the efficacy and safety of LAAO in patients with MS complicated by AF at high risk of bleeding.We recruited patients from September 2015 to September 2018. We compared the 3-year outcomes of LAAO in 21 patients with AF complicated by MS and 42 sex- and age-matched patients with AF without MS.The MS group had more cases of peripheral arterial embolism (28.6% versus 2.4%, P = 0.004), more spontaneous echo contrast (47.6% versus 9.5%, P = 0.001), a larger LAA orifice diameter (P < 0.01), and a slower LAA flow (P < 0.05) than the Non-MS group. The mean size of the selected occluder device was bigger for patients with MS than for patients with Non-MS (29.2 ± 3.7 versus 26.9 ± 3.1 mm, P = 0.014). In the first 45 follow-up days, 2 (9.5%) patients with MS had device-related thrombi (DRT); one of them had transient ischemic attack 24 hours postoperatively. From 45 days to 6 months, one patient in each group had DRT. After 6 months, two patients in the Non-MS group still had residual leaks; one of them had a stroke, with a small DRT. The proportion of dual antiplatelet therapy was higher in the Non-MS group than in the MS group (33.3% versus 4.8%, P = 0.012), but this population had an increased bleeding risk.LAAO is relatively effective and safe for preventing embolic events in patients with MS complicated by AF, at high risk of bleeding.

A Prospective, Single-Center, Phase I Clinical Trial to Evaluate the Value of Transesophageal Echocardiography in the Closure of Patent Foramen Ovale With a Novel Biodegradable Occluder.

Objective: Traditional metal alloy occluders for the closure of patent foramen ovale (PFO) may be associated with some potential complications, and may restrict the trans-septal access to the left atrium for future treatment of left-sided heart disease. Increasing attention has been paid to novel biodegradable occluders (NBOs) to achieve PFO closure. We aimed to evaluate the role of transesophageal echocardiography (TEE) in the diagnostic and anatomical evaluation of PFO, as well as in the Post-procedural assessment after transcatheter closure with a NBO. Methods: We conducted a prospective, single-center clinical study of 44 patients who were diagnosed with PFO by contrast transthoracic echocardiography (c-TTE) and TEE from June 2019 to June 2020. All patients underwent PFO occlusion with NBO under TTE guidance. Follow-up was performed at 2 days and 3 months after the procedure with TTE, and at 6 months and 1 year after the procedure with c-TTE, TTE, and TEE. Results: Interventional treatment was successfully performed in all patients. The left and right sides of the occluder device disc were significantly reduced at 3, 6, and 12 months compared to 2 days after the procedure (all P < 0.01), and decreased gradually. The thickness was significantly reduced at 12 months compared to the first three time points (all P < 0.01). Thrombus was found on the surface of the occluder device in three patients (6.4%) at 3 and 6 months after occlusion. At 6 months after procedure, there were 3 (6.8%) cases of extensive residual right-to-left shunt (RLS), 2 (4.5%) cases of moderate shunt, and 7 (15.9%) cases of small shunts. One year after procedure, 2 (4.5%) cases had a extensive residual shunt, 6 (13.6%) cases of small shunts were confirmed to originate from pulmonary veins by TEE, and the PFO-RLS occlusion rate reached 95.5%. Conclusion: This study demonstrates the feasibility, safety, and effectiveness of NBO for the closure of PFO in humans, with a high rate of complete shunt closure. Accurate TEE assessment of the PFO anatomy before closure with NBO is important to ensure that the procedure remains safe and effective. Furthermore, TEE plays a crucial role in the Post-procedure follow-up.

Observation and Optimization on Garbage Collection of Flash Memories: The View in Performance Cliff.

The recent development of 3D flash memories has promoted the widespread application of SSDs in modern storage systems by providing large storage capacity and low cost. Garbage collection (GC) as a time-consuming but necessary operation in flash memories largely affects the performance. In this paper, we perform a comprehensive experimental study on how garbage collection impacts the performance of flash-based SSDs, in the view of performance cliff that closely relates to Quality of Service (QoS). According to the study results using real-world workloads, we first observe that GC occasionally causes response time spikes, which we call the performance cliff problem. Then, we find that 3D SSDs exacerbate the situation by inducing a much higher number of page migrations during GC. To relieve the performance cliff problem, we propose PreGC to assist normal GC. The key idea is to distribute the page migrations into the period before normal GC, thus leading to a reduction in page migrations during the GC period. Comprehensive experiments with real-world workloads have been performed on the SSDsim simulator. Experimental results show that PreGC can efficiently relieve the performance cliff by reducing the tail latency from the 90th to 99.99th percentiles while inducing a little extra write amplification.

Adults with current asthma but not former asthma have higher all-cause and cardiovascular mortality: a population-based prospective cohort study.

Higher mortality in asthmatics has been shown previously. However, evidence on different asthma phenotypes on long-term mortality risk is limited. The aim was to evaluate the impact of asthma phenotypes on mortality in general population. Data from the National Health and Nutrition Examination Survey from 2001-2002 to 2013-2014 linked mortality files through December 31, 2015, were used (N = 37,015). Cox proportional hazards regression was used to estimate the risk of all-cause and cause-specific mortality adjusting for sociodemographic characteristics, smoking, body mass index, and chronic conditions. During the mean follow-up time of 7.5 years, 4326 participants died from a variety of causes. Current asthma, but not former asthma was associated with increased all-cause mortality (current asthma: HR = 1.37; 95% CI 1.20-1.58; Former asthma: HR = 0.93; 95% CI 0.73-1.18); as well as mortality from cardiovascular disease (HRCurrent = 1.41; 95% CI 1.08-1.85) and chronic lower respiratory diseases (HRCurrent = 3.17; 95% CI 1.96-5.14). In addition, we found that the HR for cardiovascular disease (CVD) mortality was slightly greater in people with childhood-onset asthma than those with adult-onset asthma. The HR for chronic lower respiratory diseases (CLRD) mortality was greater in people with adult-onset asthma than those with childhood-onset asthma. However, the differences were not statistically significant. Our study suggested that current asthma but not former asthma was associated with increased all-cause, CLRD and CVD mortality. Future well-designed studies with larger sample are required to demonstrate the association and clarify the potential mechanisms involved.

Efficacy of patent foramen ovale closure for treating migraine: a prospective follow-up study.

This study aims to evaluate the potential of percutaneous patent foramen ovale (PFO) closure to improve the headache in patients with migraine and PFO, and discuss the difference between the randomized controlled trials (RCTs) and the single-center studies. Patients of migraine with a large shunt of PFO, who experienced ≥2 headache attacks per month and failed ≥2 categories of standardized medication, underwent PFO closure in First Affiliated Hospital of Xi'an Jiao Tong University. The clinical outcomes, including frequency and duration of headache attacks, Headache Impact Test (HIT-6) score, and Visual Analogue Scale (VAS) score, were evaluated at 3, 6, and 12 months of follow-up after the PFO closure. The different efficacies of the clinical outcomes between patients with and without aura as well as different grades of PFO were also evaluated, respectively. 134 patients with migraine (39 male and 95 female) with PFO were enrolled, whose average age was 39.21±11.37 years. After PFO closure, there was a significant reduction in frequency and duration of headache attacks, HIT-6 score, and VAS score at 3, 6, and 12 months' follow-up (p<0.001). Migraine was completely relieved in 54 (40.30%) patients during 12 months' follow-up. The frequency of migraine was reduced by >50% in 44 (32.84%) patients at 3 months' follow-up and increased to 48 (35.82%) at 12 months' follow-up. 31.03% patients remained residual shunt after 6 months of closure with varying improvements of headache. This study confirmed that PFO closure can effectively reduce frequency and duration of migraine and improve quality of life, but the definitive indications and long-term effect still need further research.

Application-Oriented Data Migration to Accelerate In-Memory Database on Hybrid Memory.

With the advantage of faster data access than traditional disks, in-memory database systems, such as Redis and Memcached, have been widely applied in data centers and embedded systems. The performance of in-memory database greatly depends on the access speed of memory. With the requirement of high bandwidth and low energy, die-stacked memory (e.g., High Bandwidth Memory (HBM)) has been developed to extend the channel number and width. However, the capacity of die-stacked memory is limited due to the interposer challenge. Thus, hybrid memory system with traditional Dynamic Random Access Memory (DRAM) and die-stacked memory emerges. Existing works have proposed to place and manage data on hybrid memory architecture in the view of hardware. This paper considers to manage in-memory database data in hybrid memory in the view of application. We first perform a preliminary study on the hotness distribution of client requests on Redis. From the results, we observe that most requests happen on a small portion of data objects in in-memory database. Then, we propose the Application-oriented Data Migration called ADM to accelerate in-memory database on hybrid memory. We design a hotness management method and two migration policies to migrate data into or out of HBM. We take Redis under comprehensive benchmarks as a case study for the proposed method. Through the experimental results, it is verified that our proposed method can effectively gain performance improvement and reduce energy consumption compared with existing Redis database.

Development and validation of a novel pseudogene pair-based prognostic signature for prediction of overall survival in patients with hepatocellular carcinoma.

BACKGROUND: There is growing evidence that pseudogenes may serve as prognostic biomarkers in several cancers. The present study was designed to develop and validate an accurate and robust pseudogene pairs-based signature for the prognosis of hepatocellular carcinoma (HCC). METHODS: RNA-sequencing data from 374 HCC patients with clinical follow-up information were obtained from the Cancer Genome Atlas (TCGA) database and used in this study. Survival-related pseudogene pairs were identified, and a signature model was constructed by Cox regression analysis (univariate and least absolute shrinkage and selection operator). All individuals were classified into high- and low-risk groups based on the optimal cutoff. Subgroups analysis of the novel signature was conducted and validated in an independent cohort. Pearson correlation analyses were carried out between the included pseudogenes and the protein-coding genes based on their expression levels. Enrichment analysis was performed to predict the possible role of the pseudogenes identified in the signature. RESULTS: A 19-pseudogene pair signature, which included 21 pseudogenes, was established. Patients in high-risk group demonstrated an increased the risk of adverse prognosis in the TCGA cohort and the external cohort (all P < 0.001). The novel pseudogene signature was independent of other conventional clinical variables used for survival prediction in HCC patients in the two cohorts revealed by the multivariate Cox regression analysis (all P < 0.001). Subgroup analysis further demonstrated the diagnostic value of the signature across different stages, grades, sexes, and age groups. The C-index of the prognostic signature was 0.761, which was not only higher than that of several previous risk models but was also much higher than that of a single age, sex, grade, and stage risk model. Furthermore, functional analysis revealed that the potential biological mechanisms mediated by these pseudogenes are primarily involved in cytokine receptor activity, T cell receptor signaling, chemokine signaling, NF-κB signaling, PD-L1 expression, and the PD-1 checkpoint pathway in cancer. CONCLUSION: The novel proposed and validated pseudogene pair-based signature may serve as a valuable independent prognostic predictor for predicting survival of patients with HCC.

Identification of feature autophagy-related genes in patients with acute myocardial infarction based on bioinformatics analyses.

OBJECTIVE: To identify feature autophagy-related genes (ARGs) in patients with acute myocardial infarction (AMI) and further investigate their value in the diagnosis of AMI. METHODS: Gene microarray expression data of AMI peripheral blood samples were downloaded from the GSE66360 dataset. The data were randomly classified into a discovery cohort (21 AMI patients and 22 healthy controls) and a validation cohort (28 AMI patients and 28 healthy controls). Differentially expressed ARGs between patients with AMI and healthy controls in the discovery cohort were identified using a statistical software package. Feature ARGs were screened based on support vector machine-recursive feature elimination (SVM-RFE), and an SVM classifier was constructed. Receiver operating characteristic (ROC) analysis was used to investigate the predictive value of the classifier, which was further verified in an independent external cohort. RESULTS: A total of seven genes were identified based on SVM-RFE. The SVM classifier had an excellent discrimination ability in both the discovery cohort (area under the curve [AUC] = 0.968) and the validation cohort (AUC = 0.992), which was further confirmed in the GSE48060 dataset (AUC = 0.963). Furthermore, the SVM classifier showed outstanding discrimination between AMI patients with and without recurrent events in the independent external cohort (AUC = 0.992). The identified genes are mainly involved in the cellular response to autophagy, macroautophagy, apoptosis, and the FoxO signaling pathway. CONCLUSION: Our study identified feature ARGs and indicated their potential roles in AMI diagnosis to improve our understanding of the molecular mechanism underlying the occurrence of AMI.

Importance of Persistent Right-to-Left Shunt After Patent Foramen Ovale Closure in Cryptogenic Stroke Patients.

Percutaneous closure of patent foramen ovale (PFO) is widely performed to prevent recurrent stroke or transient ischemic attack in patients with cryptogenic stroke. However, the influence of different degrees of right-to-left shunting (RLS) has rarely been reported. We retrospectively evaluated the cases of 268 patients with cryptogenic stroke who underwent PFO closure at our hospital from April 2012 through April 2015. In accordance with RLS severity, we divided the patients into 2 groups: persistent RLS during normal breathing and the Valsalva maneuver (n=112) and RLS only during the Valsalva maneuver (n=156). Baseline characteristics, morphologic features, and procedural and follow-up data were reviewed. The primary endpoint was stroke or transient ischemic attack. More patients in the persistent group had multiple or bilateral ischemic lesions, as well as a larger median PFO diameter (2.5 mm [range, 1.8-3.9 mm]) than did patients in the Valsalva maneuver group (1.3 mm [range, 0.9-1.9 mm]) (P <0.001). Atrial septal aneurysm was more frequent in the persistent group: 25 patients (22.3%) compared with 18 (11.5%) (P=0.018). Three patients in the persistent group had residual shunting. The annual risk of recurrent ischemic stroke was similar between groups: 0.298% (persistent) and 0.214% (Valsalva maneuver). Our findings suggest that patients with persistent RLS have more numerous severe ischemic lesions, larger PFOs, and a higher incidence of atrial septal aneurysm than do those without. Although our persistent group had a greater risk of residual shunting after PFO closure, recurrence of ischemic events did not differ significantly from that in the Valsalva maneuver group.

Feasibility of Device Closure for Multiple Atrial Septal Defects With an Inferior Sinus Venosus Defect: Procedural Planning Using Three-Dimensional Printed Models.

BACKGROUND: Multiple atrial septal defects (ASD) with an inferior sinus venosus defect (SVD) have always been considered to be contraindications for interventional therapy. On the basis of early experience using a patent ductus arteriosus (PDA) occluder for interventional treatment for inferior ASD, this study investigated the feasibility of transcatheter closure of multiple ASDs with an inferior SVD under the guidance of three-dimensional (3D) printed heart models. METHODS: Between August 2016 and February 2017, five patients who were diagnosed with multiple ASDs with an inferior SVD at the First Affiliated Hospital of Xi'an Jiaotong University underwent cardiac computed tomography (CT) scans and three-dimensional (3D) echocardiography to generate heart disease models by a 3D printing technique. The best occlusion program was determined through a simulated closure on the model. Percutaneous device closure of multiple ASDs with an inferior SVD was performed following the predetermined program, guided only by fluoroscopy. Follow-up included electrocardiography, transthoracic echocardiography, and transoesophageal echocardiography. RESULTS: Three-dimensional (3D) printed models for all five patients were produced successfully. Four (4) patients had a secundum ASD with an inferior sinus venosus ASD, and one patient had a patent foramen ovale (PFO) with an inferior sinus venosus ASD. All patients were successfully treated with interventional therapy. Inferior sinus venosus ASD was percutaneously closed using the PDA occluder, and the additional secundum ASD or PFO in each patient was percutaneously closed using an ASD or PFO occluder at the same time. There was no device embolisation, procedure-related death or pericardial tamponade. During the 1-year follow-up, a minor residual shunt was detected in one patient. CONCLUSION: The use of 3D printed ASD models provides a useful reference for transcatheter device closure of multiple ASD with an inferior SVD. This approach can provide a new treatment strategy for inferior sinus venosus ASD, which has been considered a contraindication for interventional therapy. However, long-term follow-up in a large number of patients is still warranted.

Modified Method of Contrast Transthoracic Echocardiography for the Diagnosis of Patent Foramen Ovale.

PURPOSE: To compare the sensitivity and specificity of modified and traditional methods of contrast echocardiography of the right portion of the heart in patients with a suspicion of patent foramen ovale (PFO). METHODS: The study population consisted of 506 patients with high clinical suspicion of PFO. The traditional Valsalva maneuver consists of expiration against a closed glottis after a full inspiration. A modified Valsalva maneuver was performed with a handmade pressure monitoring device, which measured pressure during performance of the Valsalva maneuver. Modified and traditional methods of contrast echocardiography were performed among all patients. Contrast transesophageal echocardiography (TEE) was regarded as the gold standard. RESULTS: A total of 279 patients with PFO were confirmed by TEE. 259 cases (sensitivity: 92.83%) were detected by a modified method of contrast echocardiography of the right portion of the heart, while 234 cases were detected using the traditional method (sensitivity: 83.87%). The sensitivity of modified contrast echocardiography of the right portion of the heart was significantly higher than that of the traditional method (92.83% vs. 83.87%, P=0.001). However, there was no significant difference in the specificity of the two methods for the diagnosis of PFO (97.35% vs. 96.03%, P=0.431). Additionally, the results of semiquantitative evaluation of PFO using modified method failed to show a more positive rate than shown by the traditional method (Z=-1.782, P=0.075). CONCLUSIONS: Modified contrast echocardiography of the right portion of the heart yielded a higher sensitivity than the traditional method, which contributed to the diagnosis of cardiac PFO. The research was a part of a register study (https://register.clinicaltrials.gov/ ClinicalTrials ID: NCT02777359).