BACKGROUND:The mechanisms underlying stroke recurrence after patent foramen ovale (PFO) closure for secondary prevention remain poorly understood. This study evaluated incomplete device apposition (IDA) using cardiac CT angiography (CTA) and investigated its association with stroke recurrence. METHODS:In this prospective cohort study conducted at four centres in China (2020-2026), 233 patients (mean age: 37.01±6.73 years; 48.9% male) without known vascular risk factors were included from 382 consecutive candidates who underwent transcatheter PFO closure with follow-up ≥6 months. Cardiac CTA at 6 months post closure assessed the presence, location and extent of IDA defined as a gap between the left disc and the interatrial septum. Recurrent stroke and new-onset symptoms (atrial tachyarrhythmia, migraine headache, chest pain/discomfort) were recorded and their associations with IDA were analysed. RESULTS:IDA was observed in 55.8% of patients predominantly at the anterior-inferior rim (93.4%). IDA was significantly associated with larger and longer PFOs, larger devices and greater in vivo device thickness (p < 0.001 for all). During a median follow-up of 20.00 (IQR 18.00-24.00) months, patients with IDA had a higher risk of recurrent stroke (log-rank p = 0.022) and new-onset symptoms (log-rank p < 0.001). In eight patients who underwent repeat CTA, device apposition remained stable after 6-month closure. Pathological validation was available in one patient with severe chest pain/discomfort and a well-apposed device had sufficient endothelialisation. CONCLUSION:IDA is common after PFO closure and is associated with increased risks of recurrent stroke and new-onset symptoms. Preventive strategies warrant further investigation. TRIAL REGISTRATION NUMBER:NCT04686253.

BACKGROUND:Pulmonary regurgitation (PR) plays a vital role in the patient with post-surgical reconstruction of the right ventricular outflow tract (RVOT) or in tetralogy of Fallot. CASE SUMMARY:A 42-year-old man with a history of tetralogy of Fallot who underwent atrial septal defect repair and unclogging of the RVOT 10 years ago and pericardiectomy with valvuloplasty 2 years ago for constrictive pericarditis presented with progressive bilateral lower limb pitting edema, along with exertional dyspnea. Transthoracic echocardiography revealed RVOT stenosis, massive PR, and right ventricular dysfunction. Transcatheter pulmonary valve replacement VenusP-Valve significantly improved ventricular function. DISCUSSION:This case illustrates the efficacy of transcatheter pulmonary valve replacement in the management of RVOT obstruction and PR after complex cardiac surgery. TAKE-HOME MESSAGES:Benefits of percutaneous pulmonary value reconstruction on severe PR are limited. VenusP-Valve implantation demonstrated superior outcome and was sustained with drastic hemodynamic improvement on a severe PR patient with VenusP-Valve placement.

Pulmonary regurgitation (PR) plays a vital role in the patient with post-surgical reconstruction of the right ventricular outflow tract (RVOT) or in tetralogy of Fallot. A 42-year-old man with a history of tetralogy of Fallot who underwent atrial septal defect repair and unclogging of the RVOT 10 years ago and pericardiectomy with valvuloplasty 2 years ago for constrictive pericarditis presented with progressive bilateral lower limb pitting edema, along with exertional dyspnea. Transthoracic echocardiography revealed RVOT stenosis, massive PR, and right ventricular dysfunction. Transcatheter pulmonary valve replacement VenusP-Valve significantly improved ventricular function. This case illustrates the efficacy of transcatheter pulmonary valve replacement in the management of RVOT obstruction and PR after complex cardiac surgery. Benefits of percutaneous pulmonary value reconstruction on severe PR are limited. VenusP-Valve implantation demonstrated superior outcome and was sustained with drastic hemodynamic improvement on a severe PR patient with VenusP-Valve placement.

OBJECTIVE:Myocardial injuries resulting from hypoxia are a significant concern, and this study aimed to explore potential protective strategies against such damage. Specifically, we sought to investigate the cardioprotective effects of 16α-hydroxyestrone (16α-OHE1). METHODS:Male Sprague‒Dawley (SD) rats were subjected to hypoxic conditions simulating high-altitude exposure at 6000 m in a low-pressure chamber for 7 days. Before and during hypoxic exposure, estradiol (E2) and various doses of 16α-OHE1 were administered for 14 days. Heart weight/body weight (HW/BW), myocardial structure, Myocardial injury indicators and inflammatory infiltration in rats were measured. H9C2 cells cultured under 5% O2 conditions received E2 and varying doses of 16α-OHE1; Cell viability, apoptosis, inflammatory infiltration, and Myocardial injury indicators were determined. Expression levels of β2AR were determined in rat hearts and H9C2 cells. The β2AR inhibitor, ICI 118,551, was employed to investigate β2AR's role in 16α-OHE1's cardioprotective effects. RESULTS:Hypoxia led to substantial myocardial damage, evident in increased heart HW, CK-MB, cTnT, ANP, BNP, structural myocardial changes, inflammatory infiltration, and apoptosis. Pre-treatment with E2 and 16α-OHE1 significantly mitigated these adverse changes. Importantly, the protective effects of E2 and 16α-OHE1 were associated with the upregulation of β2AR expression in both rat hearts and H9C2 cells. However, inhibition of β2AR by ICI 118,551 in H9C2 cells nullified the protective effect of 16α-OHE1 on myocardium. CONCLUSION:Our findings suggest that 16α-OHE1 can effectively reduce hypoxia-induced myocardial injury in rats through β2ARs, indicating a promising avenue for cardioprotection.

Abstract Objective The study aimed to investigate the protective effect of 16α-OHE1 on myocardial injury caused by hypoxia.Methods and results Rats were exposed to normoxia or hypoxia conditions simulating an high altitude of 6000 m in a low-pressure chamber for 7 days. Post-exposure, evaluations were made on cardiac function, myocardial enzyme concentrations, histopathological modifications, inflammatory infiltration, and β2-adrenergic receptor (β2AR) expression levels. In parallel, H9C2 cells were cultured under standard oxygen conditions or in a three-gas incubator containing 5% O2 for 24 h. Cell viability, apoptosis, inflammatory infiltration, and myocardial enzyme levels in H9C2 cells were measured. Hypoxia induced significant myocardial damage, marked by impaired cardiac function, myocardial structural changes, inflammatory infiltration, and increased apoptosis. Pre-treatment with 16α-OHE1 significantly improved heart function and reduced myocardial enzyme release. The increased inflammatory response was also significantly suppressed. In addition to preserving myocardial structures, hypoxia-induced apoptosis in cardiomyocytes was significantly weakened. Notably, these protective effects of 16α-OHE1 were linked with the upregulation of β2AR expression. However, when β2AR was inhibited by ICI 118,551, the protective effect of 16α-OHE1 on the myocardium was abrogated.Conclusion 16α-OHE1 could reduce hypoxia-induced myocardial injury in rats through β2-adrenoceptors.

Abstract Purpose ePWV and BMI are closely related to the prediction of new-onset diabetes. The aim of this study was to evaluate the impact and predictive value of the combination of estimate pulse wave velocity (ePWV) and body mass index (BMI) on new-onset diabetic patients.Methods A secondary analysis of a cohort study conducted by rich health care was performed with a total of 211833 eligible subjects enrolled. Logistic regression analysis was used to identify factors influencing the occurrence of diabetes, and ROC curve analysis was used to evaluate the predictive value of ePWV, BMI, and their combination on new-onset diabetes.Results During a mean follow-up period of 3.12 years, 3000 men (1.41%) and 1174 women (0.55%) were diagnosed with diabetes. Logistic regression analysis showed that BMI, triglycerides, alanine aminotransferase, blood urea nitrogen, creatinine clearance rate, ePWV, and history of diabetes in the family were high-risk factors for new-onset diabetes. Compared with using ePWV or BMI alone, the combined ePWV and BMI had a higher area under the receiver operating characteristic curve of 0.822.Conclusion The elevation of ePWV and BMI levels is an independent risk factor for new-onset diabetes, and the combination of ePWV and BMI can better predict new-onset diabetes compared to using either indicator alone.

Objective:To investigate the diagnostic value of dual-source CT(DSCT)in evaluating adults with atrial septal defect(ASD)with pulmonary hypertension(PAH).Methods:Seventy-five adult patients with ASD in our hospital were retrospectively analyzed.The study sample was divided into 2 groups(PAH group(n = 40)and non-PAH group(n = 35 cases))according to the mean pulmonary artery pressure(mPAP)obtained by right cardiac catheterization(RHC)(PAH:≥25 mmHg).All patients were examined for congenital heart disease by DSCT one week before RHC.The ascending aorta diameter(AAD),main pulmonary artery diameter(MPAD),right pulmonary artery diameter(RPAD),left pulmonary artery diameter(LPAD),right lower pulmonary artery diameter(RLPAD),the maximum diameter of the short axis of both the ventricles(RVD,LVD),included the angle of the spinal ventricular septum and ASD diameter,were measured on the image.The MPAD to AAD ratio(rPA)and the RVD to LVD ratio(RVD/LVD)were calculated.Differences between the two groups in terms of clinical data,RHC indexes,and CT cardiovascular parameters were evaluated by a t-test.The ROC curve was used to determine the diagnostic efficacy of DSCT in adults with ASD and PAH.Pearson correlation coefficient was used to analyze the association between the CT parameters,mPAP,and PVR.Results:The statistically significant CT indexes between the two groups were MPAD,RPAD,LPAD,RLPAD,RVD including the angle of the spinal ventricular septum,rPA,RVD/LVD,and ASD diameter.Of these,the RPAD and LPAD including the angle of the spinal ventricular septum,rPA,RVD/LVD,and ASD diameter demonstrated moderate diagnostic efficacy for PAH(AUC＞0.7).The MPAD,rPA,and ASD diameter with mPAP were moderately positively correlated.The MPAD,rPA,and RVD/LVD with PVR were also mildly positively correlated.Furthermore,the ASD diameter and PVR were highly positively correlated.Conclusion:DSCT is diagnostically valuable for the evaluation of adults with ASD complicated with PAH.In particular,DSCT may be used to provide a comprehensive evaluation before clinical treatment,as well as for long-term follow-up and management.

Background: High-resolution optical coherence tomography can detect in situ thrombi within patent foramen ovale (PFO), which can become a dangerous embolic source. This study aimed to investigate the frequency and size of in situ thrombus within PFO using optical coherence tomography. Methods: The cross-sectional study was conducted at Fuwai Hospital (Beijing, China) between 2020 and 2021. From 528 consecutive patients with PFO, 117 (age, 34.33 [SD, 11.30] years) without known vascular risk factors were included; according to PFO-related symptoms, they were divided into the stroke (n=43, including 5 patients with transient ischemic attack), migraine (n=49) and asymptomatic (n=25) groups. Optical coherence tomography was used to evaluate in situ thrombi and abnormal endocardium within PFO. Univariable analysis and a logistic model were used to evaluate the association between stroke and in situ thrombus; age, sex, body mass index, and antithrombotic therapy were included as covariates. Results: Antithrombotic therapy was used more frequently in the stroke group than in the migraine group (76.7% versus 12.2%; P<0.001). In situ PFO thrombi were detected in 36 (83.7%), 28 (57.1%), and 0 (0.0%) patients from the stroke, migraine, and asymptomatic groups, respectively (P<0.001). Between the stroke and migraine groups, there was no significant difference in the median (interquartile range) thrombus number per patient (7 [3–12] versus 2 [0–10]; P=0.199), maximum thrombus diameter (0.35 [0.20–0.46] versus 0.21 [0–0.68] mm; P=0.597), or total thrombus volume (0.02 [0.01–0.05] versus 0.01 [0–0.05] mm3; P=0.386). Additionally, in situ thrombus was significantly associated with stroke risk (odds ratio, 4.59 [95% CI, 1.26–16.69]). Abnormal endocardium within PFO occurred in patients with in situ thrombi (71.9%) but not in those without. During optical coherence tomography examination, migraine occurred in 2 patients with in situ thrombi. Conclusions: The frequency of in situ thrombus was extremely high in stroke and migraine groups, while none of the asymptomatic individuals presented with an in situ thrombus. In situ thrombus formation may play a role in patients with PFO-associated stroke or migraines and have therapeutic implications. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04686253.

Objective Preclinical research suggests that the combined use of radiofrequency ablation and balloon dilation (CURB) could create stable interatrial communications without device implantation. This study examined the first in-human use of CURB for modified atrial septostomy in patients with severe pulmonary arterial hypertension (PAH). Methods Between July 2018 and October 2021, CURB was performed in 19 patients with severe PAH (age: 31.5±9.1 years; mean pulmonary artery pressure: 73 mm Hg (IQR: 66–92); pulmonary vascular resistance: 18.7 Wood units (IQR: 17.8–23.3)). Under guidance of intracardiac echocardiography and three-dimensional location system, (1) fossae ovalis was reconstructed and ablated point-by-point with radiofrequency; (2) then graded balloon dilation was performed after transseptal puncture and the optimal size was determined according to the level of arterial oxygen saturation (SatO 2 ); (3) radiofrequency ablation was repeated around the rims of the created fenestration. The interatrial fenestrations were followed-up serially. Results After CURB, the immediate fenestration size was 4.4 mm (IQR: 4.1–5.1) with intracardiac echocardiography, systolic aortic pressure increased by 10.2±6.9 mm Hg, cardiac index increased by 0.7±0.3 L/min/m 2 and room-air resting SatO2 decreased by 6.2±1.9% (p<0.001). One patient experienced increased pericardiac effusion postoperatively; the others had no complications. On follow-up (median: 15.5 months), all interatrial communications were patent with stable size (intraclass correlation coefficient=0.96, 95%CI:0.89 to 0.99). The WHO functional class increased by 1 (IQR: 1–2) (p<0.001) with improvement of exercise capacity (+159.5 m, P<0.001). Conclusion The interatrial communications created with CURB in patients with severe PAH were stable and the mid-term outcomes were satisfactory. Trial registration number NCT03554330 .

Pulmonary arterial hypertension (PAH) is characterized by cardiac remodelling. Glutaminolysis plays a crucial role in PAH-induced remodelling. The metabotropic glutamate receptor 5 (mGluR5) may mediate this process. This study investigated whether or not the blockade of mGluR5 may attenuate PAH-induced pathological cardiac remodelling. Pulmonary arterial hypertension was induced by intraperitoneally injecting male Sprague-Dawley (SD) rats with 60 mg/kg of monocrotaline (MCT). 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP) (10 mg/kg intraperitoneally) was used as a therapeutic intervention to block mGluR5. Cardiac functions were assessed with right heart catheterization and electrocardiography. Alterations in protein expressions and inflammatory markers were investigated using western blot and enzyme-linked immunosorbent assay (ELISA), respectively. Increased right ventricular systolic pressure (RSVP), elevated protein expressions of mGluR5, collagen types I and III and cartilage intermediate layer protein 1 (CILP1), enhanced phosphorylation of phosphatidylinositol 3-kinase (PI3K), AKT and p38 mitogen-activated protein kinase (P38MAPK), increased angiopoietin 2 (Ang 2) and vascular endothelial growth factor-α (VEGF) protein expressions and elevated serum levels of interleukin 6 (IL-6) and tumour necrotic factor α (TNF-α) were observed in MCT-induced PAH rats. MTEP improved hemodynamics and right ventricular hypertrophy. MTEP also attenuated MCT-induced elevations in the protein expressions of mGluR5, collagen types I and III, CILP1, Ang 2 and VEGF and decreased PI3K, AKT and P38MAPK phosphorylations and inflammatory cytokine levels. Metabotropic glutamate receptor 5 blockade using MTEP ameliorates PAH-induced pathological right cardiac remodelling via inhibiting the signalling cascade involving PI3K/AKT, P38MAPK, Ang 2 and VEGF.

Objective: Transcatheter closure is usually contraindicated in secundum atrial septal defect with no rim to right pulmonary vein. The morphology of an atrial septal defect is special in these patients, and the off-label use of a duct occluder might make transcatheter closure possible with the assistance of a personalized heart model. However, the related data are absent. This study was performed to investigate the off-label use of a duct occluder in the transcatheter closure of an atrial septal defect with no right pulmonary vein rim. Methods: Seven consecutive patients with an atrial septal defect (2 male/5 female; 40.1 +/- 15.2 years) with no right pulmonary vein rim were referred for attempted transcatheter closure, and a personalized heart model was produced on the basis of multislice computed tomography images. With the elastic heart model, in vitro trial occlusion was performed with a duct occluder for preoperative evaluation, and the results were compared with postoperative outcomes. Results: A single atrial septal defect was identified in 6 patients, and a double atrial septal defect was identified in another patient (1 atrial septal defect with no right pulmonary vein rim and 1 with sufficient surrounding rims). The size of the atrial septal defect was 13.4 +/- 2.2 mm, and the in vitro balloon-stretched diameter was 20.2 +/- 3.2 mm in the heart model. In vitro trial occlusion was achieved in all patients, and subsequent in vivo transcatheter closure was performed successfully with the duct occluder of the same size (24.3 +/- 3.1 mm). During follow-up (1.57 +/- 0.84 years), mild pericardial effusion was identified in 2 patients and disappeared within 3 months. No other complications occurred. Conclusions: By using a personalized heart model, the off-label use of a duct occluder is feasible and safe in the transcatheter closure of an atrial septal defect with no right pulmonary vein rim. Further research is required to evaluate the long-term outcomes.

OBJECTIVE:Though successful transcatheter closure has been reported in secundum atrial septal defect (ASD) with deficient posterior-inferior rim, it is still difficult to screen the appropriate candidates. Three-dimensional printing (3DP) makes in vitro trial occlusion possible, and might provide a feasible method in the prediction of successful closure. METHODS:Thirty-five consecutive ASD patients (10M/25F, age, 47.7 ± 11.8 years) with deficient posterior-inferior rim (≤3 mm) were referred for attempted transcatheter closure, and personalized heart model (elastic rubber) was produced based on end-systolic MSCT images. The in vitro measurement and trial occlusion were performed for preoperative evaluation (in vitro successful/unsuccessful group), and the results were compared with postoperative outcomes. RESULTS:Successful in vitro occlusion was achieved in 30 patients (7M/23F), and the size of ASD was 27.1 ± 4.4 mm. The posterior-inferior rim was 0.95 ± 1.22 mm (rim defect in 17 patients), and 12 patients were associated with aortic rim deficiency. The subsequent transcatheter closure was performed successfully in 29 patients, and the occluder-diameter was identical to that of in vitro occlusion (35.0 ± 4.4 mm). The follow-up (1.4 ± 0.58 years) showed no residual shunt and related-complications. In unsuccessful in vitro group (n = 5), the range of rim deficiency was wider (P = 0.019) and the rim to inferior vena cava was shorter (4.60 ± 2.07 mm vs. 10.71 ± 5.28 mm, P = 0.016). Furthermore, transcatheter closure failed in all patients. CONCLUSIONS:In ASD with deficient posterior-inferior rim, 3DP allows accurate determination of the size and surrounding rims of ASD. Based on personalized heart model, in vitro trial occlusion is an effective method to identify the appropriate candidates for transcatheter closure.

Objective To assess the safety and efficiency of robotic minimally invasive surgery and transcatheter interventional occlusion for treatment of adult secundum atrial septal defect (ASD) by comparing the early and recent postoperative follow-up results of the two minimally invasive surgery. Methods Thirty adult patients with secundum ASD, who admitted to the General Hospital of PLA from Jan. 2008 to Dec. 2014 and received treatment of da Vinci Surgical System, were recruited as TEASD-R group, meanwhile, another 30 adult patients who received transcatheter interventional occlusion were recruited under the strict 1:1 criterion as TIASD-O group. The early postoperative complications, in-hospital conditions, recent postoperative follow-up results and the quality of life 30d and 6 months after operation were compared and retrospectively analyzed between the two groups. Results The success rates of surgery were 100% in the both groups, no early and recent postoperative complications (residual shunt, pericardial effusion, cerebral infarction, peripheral vascular embolism, new arrhythmia, etc.) were found in TEASD-R group. While some of corresponding complications existed in TISAD-O group, and the differences were of statistical significance (P<0.05) between the two groups in the incidence of postoperative new arrhythmia, tricuspid incompetence and pulmonary hypertension, as well as in the early size of right atrium and in-hospital time. SF-36 quality of life questionnaire showed that the difference of somatic pain 30d after operation was of statistical significance (P<0.05) between the two groups, but the difference disappeared 6 months after operation. Conclusion Robotic minimally invasive surgery for adult secundum ASD is feasible, safe and efficacious since no postoperative complications occurred such as tricuspid incompetence and pulmonary hypertension, but the longer operative and inhosptial time are the shortages of the operation. DOI: 10.11855/j.issn.0577-7402.2016.05.11

OBJECTIVE:To evaluate the efficacy of atrial septostomy in idiopathic pulmonary arterial hypertension (IPAH) patients complicating right ventricular failure.METHODS:This retrospective analysis included 5 IPAH patients (3 males, (29.3±15.2) years old) with right ventricular failure which were refractory to conventional and target-specific medication in Shanghai Chest Hospital from March to July 2014. Graded balloon dilation septostomy procedures were performed in all 5 patients.RESULTS:Successful atrial septostomy was achieved in 5 attempts with no procedure-related complications. Immediately post procedure, the mean systemic oxygen saturation decreased from (98.0±1.8)% to (86.4±3.2)% (P = 0.002), while the mean right atrial pressure decreased from (18.9±1.7) mmHg (1 mmHg = 0.133 kPa) to (16.0±1.3) mmHg (P = 0.039) and the mean cardiac index increased from (2.1±0.3) L · min(-1) · m(-2) to (2.7±0.5) L · min(-1) · m(-2) (P = 0.029). Mean follow-up was (6.2 ±1.8) months. Cardiac functional class (WHO) was 3 in 3 patients and 4 in 2 patients before the procedure, and increased 1 class in all patients during follow-up (P = 0.062). Exercise endurance (6-min walk test) also improved from (289.2±16.9) m to (320.4±19.6) m (P = 0.019), while B-type natriuretic peptide (BNP) level declined from (550.0±35.7) ng/L to (218.0±36.2) ng/L (P < 0.001). Except one patient developed spontaneous closure of created defect, right to left shunt at atrial septal level was evidenced by echocardiography during follow-up in the rest 4 patients.CONCLUSIONS:Atrial septostomy is safe and can improve hemodynamics and heart function in selected IPAH patients with right heart failure. Atrial septostomy can be used as a palliative treatment for IPAH and further study is warranted to evaluate the long-term efficacy of this procedure.

OBJECTIVES:To evaluate the efficacy and safety of the new device Amplatzer Duct Occluder II (ADO II) for the closure of coronary artery fistulae (CAF) with coronary anomaly.BACKGROUND:Transcatheter device closure is an alternative treatment for selective patients with CAF. The currently available reports regarding the closure of CAF with the ADO II are limited.METHODS:From April 1, 2011 to July 15, 2012, 5 patients (3 males and 2 females) aged from 3 years to 27 years old (median age 5 years old) underwent CAF closure with the ADO II. The immediate and short-term outcomes were evaluated.RESULTS:ADO II was deployed via the femoral vein (2 cases), femoral artery (1 case), brachial artery (1 case), and radial artery (1 case). There were no complications during all the procedures. The median fluoroscopy and procedural times were 20 and 39 minutes, respectively. Immediate trivial and mild residual shunt was present in one patient, respectively, but disappeared 24 hours after the procedure, and there was no recanalization at a median follow-up of 6 months.CONCLUSIONS:The new device ADO II was safely deployed with complete resolution of CAF shunt with tortuous coronary artery to the drainage. The reduced sheath sizes and softer shape of this device allow for venous or arterial approach. The ADO II might be a preferable alternative device for closure of small-tortuous CAFs.