The association of right ventricular-pulmonary arterial coupling and pulmonary vascular resistance in adult patients with uncorrected atrial septal defect.

BACKGROUND: Atrial septal defects (ASD) are the most common type of adult congenital heart disease (ACHD) associated with a high risk developing of pulmonary arterial hypertension (PAH). ASD closure is not recommended in patients with PAH and Pulmonary Vascular Resistance (PVR) ≥ 5 Wood Unit (WU). Noninvasive methods have been proposed to measure PVR; however, their accuracy remains low. Right Ventricle (RV) - Pulmonary Artery (PA) coupling is defined as the ability of the RV to adapt to high-resistance conditions. Tricuspid Annular Plane Systolic Excursion (TAPSE)/estimated pulmonary artery systolic pressure (ePASP) calculation using echocardiography is a noninvasive technique that has been proposed as a surrogate equation to evaluate RV-PA coupling. Currently, no research has demonstrated a relationship between RV-PA coupling and PVR in patients with ASD. METHODS: The study participants were consecutive eligible patients with ASD who underwent right heart catheterization (RHC) and echocardiography at Hasan Sadikin General Hospital, Bandung. Both the procedures were performed on the same day. RV-PA Coupling, defined as TAPSE/ePASP > 0.31, was assessed using echocardiography. The PVR was calculated during RHC using the indirect Fick method. RESULTS: There were 58 patients with ASD underwent RHC and echocardiography. Among them, 18 had RV/PA Coupling and 40 had RV/PA Uncoupling. The PVR values were significantly different between the two groups (p = 0.000). Correlation test between TAPSE/ePASP with PVR showed moderate negative correlation (r= -0.502, p = 0.001). TAPSE/ePASP ≤ 0.34 is the cutoff point to predict PVR > 5 WU with sensitivity of 91.7% and specificity 63.6%. CONCLUSION: This study showed a moderate negative correlation between TAPSE/ePASP and PVR. TAPSE/ePASP ≤ 0.34 could predict PVR > 5 WU with good sensitivity.

Quantitative evaluation of right ventricular myocardial function changes in patients with atrial septal defect before and after occlusion by noninvasive right ventricular pressure-strain loop.

OBJECTIVE: The noninvasive right ventricular pressure-strain loop (PSL) represents a novel method for the quantitative assessment of right ventricular myocardial function. Given that atrial septal defect (ASD) is a prevalent congenital heart anomaly associated with right ventricular volume overload, this study aimed to quantitatively assess the myocardial function of the right ventricle in ASD patients pre- and post-occlusion by noninvasive right ventricular PSL. METHODS: This study included 36 patients diagnosed with secundum ASD group and 30 healthy adults (control group). We compared conventional right ventricular echocardiographic parameters, right ventricular strain, and myocardial work in the ASD group before occlusion, two days post-occlusion, and three months post-occlusion, with those in the control group. RESULTS: Prior to and two days following occlusion, the ASD group exhibited higher right ventricular global work index (RVGWI), right ventricular global wasted work (RVGWW), and right ventricular global constructive work (RVGCW) compared to the control group (P < .05). Within the ASD group, post-occlusion, RVGWI, RVGCW, and RVGWW values were significantly reduced compared to pre-occlusion values (P < .001). Furthermore, RVGWI and RVGCW showed a significant decrease three months after occlusion compared to two days post-occlusion (P < .05). Multivariate regression analysis identified ASD diameter and pulmonary artery systolic pressure (PASP) as independent predictors of RVGWI (ß = .405, P < .001; ß = 2.307, P = .037) and RVGCW(ß = .350, P<.001; ß = 1.967, P = .023). CONCLUSIONS: The noninvasive right ventricular PSL effectively demonstrates the alterations in right ventricular myocardial function in ASD patients, pre- and post-occlusion. The metrics of right ventricular myocardial work (RVMW) offer a novel indicator for evaluating right ventricular myocardial function in these patients. Moreover, ASD diameter and PASP emerge as independent determinants of RVGWI and RVGCW.

Molecular Pathways and Animal Models of Atrial Septal Defect.

The relative simplicity of the clinical presentation and management of an atrial septal defect belies the complexity of the developmental pathogenesis. Here, we describe the anatomic development of the atrial septum and the venous return to the atrial chambers. Experimental models suggest how mutations and naturally occurring genetic variation could affect developmental steps to cause a defect within the oval fossa, the so-called secundum defect, or other interatrial communications, such as the sinus venosus defect or ostium primum defect.

Molecular Pathways and Animal Models of Atrioventricular Septal Defect.

The development of a fully functional four-chambered heart is critically dependent on the correct formation of the structures that separate the atrial and ventricular chambers. Perturbation of this process typically results in defects that allow mixing of oxygenated and deoxygenated blood. Atrioventricular septal defects (AVSD) form a class of congenital heart malformations that are characterized by the presence of a primary atrial septal defect (pASD), a common atrioventricular valve (cAVV), and frequently also a ventricular septal defect (VSD). While AVSD were historically considered to result from failure of the endocardial atrioventricular cushions to properly develop and fuse, more recent studies have determined that inhibition of the development of other components of the atrioventricular mesenchymal complex can lead to AVSDs as well. The role of the dorsal mesenchymal protrusion (DMP) in AVSD pathogenesis has been well-documented in studies using animal models for AVSDs, and in addition, preliminary data suggest that the mesenchymal cap situated on the leading edge of the primary atrial septum may be involved in certain situations as well. In this chapter, we review what is currently known about the molecular mechanisms and animal models that are associated with the pathogenesis of AVSD.

Evaluation of Inter-atrial Septal Defect Diameter and Left Ventricular Systolic Function in Children with Ostium Secundum Atrial Septal Defect in Enugu, Nigeria.

BACKGROUND: Children with ostium secundum atrial septal defect (OS ASD) usually present with varying degrees of ventricular dysfunction. OBJECTIVES: This study aimed to evaluate the left ventricular systolic function of children with OS ASD compared with control. METHODS: This was a cross-sectional study involving 113 children with OS ASD and 113 age- and sex- matched controls. Their age ranged from 1 month to 16 years. There were 49 males and 64 females in each group. Left ventricular systolic function of children with isolated OS ASD were compared with that of controls using echocardiography. Subjects and controls who fulfilled the inclusion criteria were consecutively recruited in the study. The data elicited from the study were analyzed with the IBM SPSS version 20 (IBM Corp, Chicago). RESULTS: The mean left ventricular mass (LV mass) of the control, 93.9±113.6 gm was significantly higher than that of subjects with OS ASD, 39.4±74.3 gm, (Mann Whitney U= 4.266, p< 0.001). Similarly, the mean left ventricular internal diameter in diastole (LVIDd) of the control,25.8±11.7 mm was significantly higher than that of participants with OS ASD, 19.9±7.1 mm (Mann Whitney U=4.522, p<0.001). The mean interventricular septal diameter in systole (IVSs) of the control, 7.2±3.5 mm was higher than that of participants with OS ASD, 5.0±1.9 mm and the mean difference was found to be statistically significant, (Student t=5.738, p<0.001). The mean left ventricular internal diameter in systole (LVIDs) of the control, 16.2±7.6 mm was significantly higher than that of participants with OS ASD, 12.9±5.8 mm, (Student t= 3.660, p< 0.001). There was no significant correlation between the size of interatrial septal defect of children with OS ASD and left ventricular systolic function and age :(Corr. Coef. 0.065, p= 0.492) ; EF( Corr. Coef. 0.121,p=0.202), FS (Corr. Coef. 0.139, p=0.143). CONCLUSION: Children with OS ASD had lower left ventricular mass compared with those with control. Females seem to have higher function than males.

CONTEXTE: Les enfants atteints de communication interauriculaire type ostium secundum (CIASOS) présentent généralement des degrés variables de dysfonction ventriculaire. OBJECTIFS: Cette étude visait à évaluer la fonction systolique ventriculaire gauche des enfants atteints de CIASOS par rapport à des témoins. MÉTHODES: Il s'agissait d'une étude transversale portant sur 113 enfants atteints de CIASOS et 113 témoins appariés selon l'âge et le sexe. Leur âge variait de 1 mois à 16 ans. Il y avait 49 garçons et 64 filles dans chaque groupe. La fonction systolique ventriculaire gauche des enfants présentant un CIASOS isolé a été comparée à celle des témoins à l'aide de l'échocardiographie. Les sujets et les témoins qui remplissaient les critères d'inclusion ont été recrutés consécutivement dans l'étude. Les données recueillies ont été analysées avec la version 20 d'IBM SPSS (IBM Corp, Chicago). RÉSULTATS: La masse moyenne du ventricule gauche (VG) du groupe témoin, 93,9±113,6 g, était significativement plus élevée que celle des sujets atteints d'OS ASD, 39,4±74,3 g (Mann-Whitney U = 4,266, p < 0,001). De même, le diamètre interne moyen du ventricule gauche en diastole (LVIDd) du groupe témoin, 25,8±11,7 mm, était significativement plus élevé que celui des participants atteints d'OS ASD, 19,9±7,1 mm (Mann-Whitney U = 4,522, p < 0,001). Le diamètre moyen du septum interventriculaire en systole (IVSs) du groupe témoin, 7,2±3,5 mm, était plus élevé que celui des participants atteints d'OS ASD, 5,0±1,9 mm, et la différence moyenne était statistiquement significative (Student t = 5,738, p < 0,001). Le diamètre interne moyen du ventricule gauche en systole (LVIDs) du groupe témoin, 16,2±7,6 mm, était significativement plus élevé que celui des participants atteints d'OS ASD, 12,9±5,8 mm (Student t = 3,660, p < 0,001). Il n'y avait pas de corrélation significative entre la taille du défaut septal interauriculaire chez les enfants atteints d'OS ASD et la fonction systolique du ventricule gauche et l'âge : (Coef. Corr. 0,065, p = 0,492) ; FE (Coef. Corr. 0,121, p = 0,202), FS (Coef. Corr. 0,139, p = 0,143). CONCLUSION: Les enfants atteints de CIASOS avaient une masse ventriculaire gauche plus faible que ceux du groupe témoin. Les filles semblent avoir une fonction plus élevée que les garçons. MOTS-CLÉS: Fonction ventriculaire gauche; Communication interauriculaire type ostium secundum (CIASOS); Malformation septale interauriculaire; Enfants; Échocardiographie.

Effect of Renal and Left Ventricular Function on Serial Pulmonary Arterial Pressure Changes after Device Closure of Atrial Septal Defect.

BACKGROUND: The age of candidates for device closure of atrial septal defect (ASD) has been increasing. Thus, concerns exist about dyspnea aggravation or atrial fibrillation development after device closure due to augmentation of left ventricular (LV) and left atrial (LA) preload. This study aimed to examine patterns and determinants of serial pulmonary arterial pressure and left ventricular filling pressure changes after device closure of ASD. METHODS: Among the 86 consecutive patients who underwent percutaneous device closure of ASD, those with end-stage renal disease or those without pre- or postprocedural Doppler data were excluded. The clinical, transesophageal, and transthoracic echocardiographic findings of 78 patients were collected at baseline, one-day postprocedure, and one-year follow-up. RESULTS: The mean age of study patients was 49.8 ± 15.0 years, and the average maximal defect diameter and device size were 20.2 ± 6.0 mm and 23.8 ± 6.4 mm. Four patients (5.6%) underwent new-onset atrial fibrillation, and five patients (6.4%) took diuretics within one-year after closure. Some patients (n = 21; 27%) exhibited paradoxically increased tricuspid regurgitant velocity (TRV) one-day postprocedure; they also were older with lower e', glomerular filtration rate, and LV ejection fraction and a higher LA volume index. However, even in these patients, TRV deceased below baseline levels one-year later. Both E/e' and LA volume index significantly increased immediately after device closure, but all decreased one-year later. Larger defect size and higher TRV were significantly correlated with immediate E/e' elevation. CONCLUSION: In older, renal, diastolic, and systolic dysfunctional patients with larger LA and scheduled for larger device implantation, peri-interventional preload reduction therapy would be beneficial.

The M310T mutation in the GATA4 gene is a novel pathogenic target of the familial atrial septal defect.

BACKGROUND: Although most cases of atrial septal defect (ASD) are sporadic, familial cases have been reported, which may be caused by mutation of transcription factor GATA binding protein 4 (GATA4). Herein we combined whole-exome sequencing and bioinformatics strategies to identify a novel mutation in GATA4 accounting for the etiology in a Chinese family with ASD. METHODS: We identified kindred spanning 3 generations in which 3 of 12 (25.0%) individuals had ASD. Punctilious records for the subjects included complete physical examination, transthoracic echocardiography, electrocardiograph and surgical confirming. Whole-exome capture and high-throughput sequencing were performed on the proband III.1. Sanger sequencing was used to validate the candidate variants, and segregation analyses were performed in the family members. RESULTS: Direct sequencing of GATA4 from the genomic DNA of family members identified a T-to-C transition at nucleotide 929 in exon 5 that predicted a methionine to threonine substitution at codon 310 (M310T) in the nuclear localization signal (NLS) region. Two affected members (II.2 and III.3) and the proband (III.1) who was recognized as a carrier exhibited this mutation, whereas the other unaffected family members or control individuals did not. More importantly, the mutation GATA4 (c.T929C: p.M310T) has not been reported previously in either familial or sporadic cases of congenital heart defects (CHD). CONCLUSIONS: We identified for the first time a novel M310T mutation in the GATA4 gene that is located in the NLS region and leads to family ASD with arrhythmias. However, the mechanism by which this pathogenic mutation contributes to the development of heart defect and tachyarrhythmias remains to be ascertained.

Electrical storm after correction of an uncomplicated congenital atrial septal defect in an adult: a case report.

BACKGROUND: There is a paucity of published literature describing electrical storm after the correction of uncomplicated atrial septal defect (ASD) in an adult. CASE PRESENTATION: We present a 49-year-old woman with a congenital ASD combined with mild tricuspid regurgitation who denied any history of arrhythmia or other medical history. She suffered from electrical storm (≥ 3 episodes of ventricular tachycardias or ventricular fibrillations) in the early stage after ASD repair with combined tricuspid valvuloplasty. During electrical storm, her electrolytes were within normal ranges and no ischemic electrocardiographic changes were detected, which suggested that retained air embolism or acute coronary thrombosis were unlikely. Additionally, echocardiographic findings and her central venous pressure (5-8 mmHg during the interval between attacks) failed to support the diagnosis of pericardial tamponade. After a thorough discussion, the surgeons conducted an emergent re-exploration and repeated closure of the ASD with combined DeVega's annuloplasty. Eventually, the patient recovered uneventfully, without reoccurring arrhythmias during follow-up. Although we fail to determine the definite cause, we speculate that the causes probably are iatrogenic injury of the conduction system due to a rare anatomic variation, poor intraoperative protection, latent coronary distortion during tricuspid valvuloplasty, or idiopathic or secondary abnormalities of the conduction system. CONCLUSIONS: For most surgeons, performing re-exploration without a known etiology is a difficult decision to make. This case illustrates that re-exploration could be an option when electrical storm occurs in the early stage postoperatively. Nevertheless, surgeons should assess the benefit-risk ratio when taking this unconventional measure.

Late recovery of the cardiopulmonary exercise capacity after transcatheter amplatzer device closures for atrial septal defects in adults.

Transcatheter atrial septal defect (ASD) closures using an Amplatzer Septal Occluder (ASO) have been widely performed. Compared to children, we sometimes experience late recovery of exercise performance in adult patients. Our study aimed to evaluate the change in the cardiopulmonary exercise capacity in asymptomatic or mildly symptomatic adult patients after a transcatheter ASD closure using an ASO. The subjects consisted of 29 patients (age 39.5 ± 13.6 years) that underwent cardiopulmonary exercise testing (CPX) before, 3, 6, and 12 months after a transcatheter secundum ASD closure using an ASO. The peak oxygen consumption (peak VO2), anaerobic threshold (AT), and slope of the correlation between the ventilation and carbon dioxide production (VE/VCO2 slope) were evaluated. We also evaluated the left-ventricular end-diastolic diameter (LVEDD), right-ventricular end-diastolic dimension (RVEDD) by echocardiography, and hemodynamic values by cardiac catheterization before the ASO procedure. The peak VO2 did not show any improvement 3 months after the ASO procedure; however, a significant improvement was displayed 6 and 12 months (baseline: 23.4 ± 6.3, 3 months: 23.6 ± 6.4, 6 months: 25.1 ± 5.6, 12 months: 26.4 ± 5.3 mL/kg/min; p < 0.001) after the ASO. The LVEDD (before: 38.1 ± 3.6, 3 months: 43.4 ± 3.4 mm; p < 0.001) and RVEDD (before: 33.6 ± 5.3, 3 months: 26.3 ± 2.6 mm; p < 0.001) on echocardiography quickly improved 3 months after the ASO. Although the LVEDD and RVEDD normalized 3 months after the ASO, the peak VO2 still decreased; however, the peak VO2 improved to almost a normal range 6 months after the ASO.

Interventional Therapy Versus Medical Therapy for Secundum Atrial Septal Defect: A Systematic Review (Part 2) for the 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Secundum atrial septal defect (ASD) is the most common adult congenital heart defect and can present with wide variation in clinical findings. With the intention of preventing morbidity and mortality associated with late presentation of ASD, consensus guidelines have recommended surgical or percutaneous ASD closure in adults with right heart enlargement, with or without symptoms. The aim of the present analysis was to determine if the protective effect of secundum ASD closure in adults could be qualified by pooling data from published studies. A systematic review and meta-analysis were performed by using EMBASE, MEDLINE (through PubMed), and the Cochrane Library databases to assess the effect of secundum ASD percutaneous or surgical closure in unoperated adults ≥18 years of age. Data were pooled across studies with the DerSimonian-Laird random-effects model or a Bayesian meta-analysis model. Between-study heterogeneity was assessed with Cochran's Q test. Bias assessment was performed with the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool, and statistical risk of bias was assessed with Begg and Mazumdar's test and Egger's test. A total of 11 nonrandomized studies met the inclusion criteria, contributing 603 patients. Pooled analysis showed a protective effect of ASD closure on New York Heart Association functional class and on right ventricular systolic pressure, volumes, and dimensions. Two additional studies comprising 652 patients were reviewed separately for mortality outcome and primary outcome of interest because they did not meet the inclusion criteria. Those studies showed that ASD closure was associated with a weak protective effect on adjusted mortality rate but no significant impact on atrial arrhythmias in patients >50 years of age. Across all studies, there was significant heterogeneity between studies for nearly all clinical outcomes. The overall body of evidence was limited to observational cohort studies, the limitations of which make for low-strength evidence. Even within the parameters of the included studies, quality of evidence was further diminished by the lack of well-defined clinical outcomes. In conclusion, pooled data analysis on the impact of secundum ASD closure in adults was notably limited because of the lack of randomized controlled trials in patients with only secundum ASD. The few cohort studies in this population demonstrated improvement in functional status and right ventricular size and function as shown by echocardiogram. However, our findings suggest that at the time of this publication, insufficient data are available to determine the impact of ASD repair on mortality rate in adults.

Prediction of hemodynamics after atrial septal defect closure using a framework of circulatory equilibrium in dogs.

In patients with heart failure, atrial septal defect (ASD) closure has a risk of inducing life-threatening acute pulmonary edema. The objective of this study was to develop a novel framework for quantitative prediction of hemodynamics after ASD closure. The generalized circulatory equilibrium comprises right and left cardiac output (CO) curves and pulmonary and systemic venous return surfaces. We incorporated ASD into the framework of circulatory equilibrium by representing ASD shunt flow (QASD) by the difference between pulmonary flow (QP) and systemic flow (QS). To examine the accuracy of prediction, we created ASD in six dogs. Four weeks after ASD creation, we measured left atrial pressure (PLA), right atrial pressure (PRA), QP, and Qs before and after ASD balloon occlusion. We then predicted postocclusion hemodynamics from measured preocclusion hemodynamics. Finally, we numerically simulated hemodynamics under various ASD diameters while changing left and right ventricular function. Predicted postocclusion PLA, PRA, and QS from preocclusion hemodynamics matched well with those measured [PLA: coefficient of determination (r2) = 0.96, standard error of estimate (SEE) = 0.89 mmHg, PRA: r2 = 0.98, SEE = 0.26 mmHg, QS: r2 = 0.97, SEE = 5.6 mL·min-1·kg-1]. A simulation study demonstrated that ASD closure increases the risk of pulmonary edema in patients with impaired left ventricular function and normal right ventricular function, indicating the importance of evaluation for the balance between right and left ventricular function. ASD shunt incorporated into the generalized circulatory equilibrium accurately predicted hemodynamics after ASD closure, which would facilitate safety management of ASD closure.NEW & NOTEWORTHY We developed a framework to predict the impact of atrial septal defect (ASD) closure on hemodynamics by incorporating ASD shunt flow into the framework of circulatory equilibrium. The proposed framework accurately predicted hemodynamics after ASD closure. Patient-specific prediction of hemodynamics may be useful for safety management of ASD closure.

Pulmonary hemodynamics and wave reflections in adults with atrial septal defects.

Using high-fidelity micromanometers and flow velocity sensors at right heart catheterization, we compared pulmonary hemodynamics and wave reflections in age-matched normal adults and those with atrial septal defects, separated into three subgroups based on levels of mean pulmonary artery pressure: low (<17 mmHg), intermediate (17-26 mmHg), high (>26 mmHg). We made baseline measurements in all groups and after intravenous sodium nitroprusside in the subgroups. All of the subgroups had higher than normal baseline pulmonary flows and corresponding power that did not differ among the subgroups. The pulmonary vascular resistance, input resistance, and characteristic impedance in the subgroups did not differ from normal. Aside from the elevated flow and power, the hemodynamics in the low subgroup did not differ from normal. The intermediate subgroup had significantly higher than normal right ventricular and pulmonary artery pressures, wave reflections, and shorter wave reflection time, which all reverted to normal after nitroprusside. The high subgroup had similar changes as the intermediate subgroup. Unlike that subgroup, however, the pressures, wave reflections, and reflection return time did not revert to normal after nitroprusside. Hence, elevated wave reflections, but not resistance or characteristic impedance, are the hallmark of pulmonary hypertension in adults with atrial septal defects. Our results demonstrate that detailed measurements of hemodynamics and assessment of responsiveness to vasodilators provide important information about the pulmonary circulation in atrial septal defect. Coupled with studies after defect closure, those results may be a better foundation than current ones for clinical decisions.

Haemodynamics of an iatrogenic atrial septal defect after MitraClip implantation.

BACKGROUND: The MitraClip procedure requires transseptal access of the left atrium with a 24F guiding sheath. We evaluated invasively whether a MitraClip induced iatrogenic atrial septal defect (IASD) leads to development of a relevant interatrial shunt and right ventricular overload. METHODS: A total of 69 patients who underwent a MitraClip procedure due to a severe mitral valve regurgitation (MVR) were included in the observational, retrospective cohort study. All pressures were directly measured throughout the procedure. Cardiac index (CI), systemic (Qs) and pulmonary (Qp) flow were calculated using the Fick method. RESULTS: Successful MitraClip implantation increased CI (2.5 ± 0.62 vs 3.05 ± 0.77 L/min/m2 ; P < .0001), whereas SVR (1491 ± 474 vs 997 ± 301 dyn s/cm5 ; P < .0001), PVR (226 ± 121 vs 188 ± 96 dyn/s/cm5 ; P = .04), PCWP (23 ± 6.1 vs 20 ± 4.7 mm Hg; P = .0031), PA pressure (33.6 ± 7.2 vs 31.9 ± 6.6 mm Hg; P = .1437) and LA pressure (21.5 ± 5.4 vs 18.7 ± 4.9 mm Hg; P < .0001) all decreased. The effect on LA pressure was further enhanced by guiding catheter retrieval (14.4 ± 4.6 mm Hg; P < .0001). At the end of the procedure, Qp (6.033 ± 1.3 L/min) exceeded Qs (5.537 ± 1.3 L/min) by 0.496 L/min leading to a Qp:Qs ratio of 1.09 (P = .007). After 6 months, echocardiography revealed no changes in RV diameter (42.96 ± 6.95 mm vs 43.81 ± 7.67 mm; P = .62) and TAPSE (17.13 ± 3.33 mm vs 17.36 ± 3.24 mm; P = .48). CONCLUSION: Our data show that the MitraClip procedure does not induce a relevant interatrial shunt or right ventricular overload. In fact, future studies will have to show whether the IASD may even be beneficial in selected patient populations by left atrial volume and pressure relief.

Cardiac manifestations and gene mutations of patients with RASopathies in Taiwan.

RASopathies are developmental diseases caused by mutations in rat sarcoma-mitogen-activated protein kinase pathway genes. These disorders, such as Noonan syndrome (NS) and NS-related disorders (NSRD), including cardio-facio-cutaneous (CFC) syndrome, Costello syndrome (CS), and NS with multiple lentigines (NSML; also known as LEOPARD syndrome), have a similar systemic phenotype. A wide spectrum of congenital heart disease and hypertrophic cardiomyopathy (HCMP) can exhibit major associated characteristics. A retrospective study was conducted at the Mackay Memorial Hospital, National Taiwan University Hospital, Buddhist Tzu-Chi General Hospital, Chang-Gung Memorial Hospital, Taichung Veterans General Hospital, and Chung Shan Medical University Hospital from January 2007 to December 2018. We reviewed the clinical records of 76 patients with a confirmed molecular diagnosis of RASopathies, including NS, CS, CFC syndrome, and NSML. We evaluated the demographic data and medical records with clinical phenotypes of cardiac structural anomalies using cross-sectional and color Doppler echocardiography, electrocardiographic findings, and follow-up data. A total of 47 (61.8%) patients had cardiac abnormalities. The prevalence of cardiac lesions according to each syndrome was 62.7, 50.0, 60.0, and 66.7% in patients with NS, CFC syndrome, CS, and NSML, respectively. An atrial septal defect was usually combined with other cardiac abnormalities, such as pulmonary stenosis (PS), HCMP, ventricular septal defect, or patent ductus arteriosus. Patients with NS most commonly showed PS. In patients with NSRD and cardiac abnormalities, HCMP (29.4%) was the most commonly observed cardiac lesion. PTPN11 was also the most frequently detected mutation in patients with NS and NSRD. Cardiac abnormalities were the most common symptoms observed in patients with RASopathies at the time of their first hospital visit. Performing precise analyses of genotype-cardiac phenotype correlations in a larger cohort will help us accurately diagnose RASopathy as soon as possible.

Here today, gone tomorrow: Outcomes of residual leak following secundum atrial septal defect closure with the GORE CARDIOFORM Septal Occluder.

OBJECTIVE: To assess the outcomes and potential predictors of residual leak after implantation of the GORE CARDIOFORM Septal Occluder (GSO) in secundum atrial septal defects (ASDs). BACKGROUND: The non-self-centering design of the GSO could lead to residual leak at the edge of the device. Outcomes of residual leak are poorly understood. METHODS: Retrospective, multicenter review of patients treated with the GSO for the pivotal and continued access study. Procedural, echocardiographic, and follow up data were reviewed. Multivariate analysis was performed to determine predictors of leak at implant and outcomes of these leaks. RESULTS: There were 370 total ASD device closures with the GSO, 65 (17.56%) of which were found to have residual leak at implantation. Patients with residual leak had larger defects (10.33 ± 3.05 mm vs. 9.13 ± 2.89 mm, p = .006) and smaller aortic rims (4.87 ± 3.33 mm vs. 6.17 ± 3.78 mm, p = .019), as compared to those without leak. Larger devices were implanted (p = .008) and more devices per case (p = .007) were utilized in the residual leak cohort as compared to those without leak. Overall, among patients with residual leak, there was a significant decrease in leak size over 1 year, from 1.55 ± 0.75 mm to 0.25 ± 0.74 mm (p < .001), with the majority (87.6%) disappearing by 12-month follow-up. CONCLUSIONS: Residual leak at implantation can be seen after ASD device closure with the GSO, more commonly in larger defects with smaller retroaortic rims. The vast majority of these leaks completely resolve by 1 year follow up.

Transcatheter closure of sinus venosus atrial septal defect with anomalous pulmonary venous drainage: Innovative technique with long-term follow-up.

INTRODUCTION: Surgical closure of sinus venosus atrial septal defect (SVASD) is the standard management. A safe and effective transcatheter approach will be an attractive option. OBJECTIVES: To assess the feasibility and long-term safety of transcatheter closure of SVASD with anomalous pulmonary venous drainage. PATIENTS AND METHODS: From July 2011 to October 2013, four patients with large SVASD and anomalous right upper pulmonary venous (RUPV) drainage underwent transcatheter closure of their defects at Ibn-Albitar Center for Cardiac Surgery, Baghdad, Iraq. Two patients with superior vena cava (SVC)-type SVASD underwent closure using covered Cheatham-Platinum (CP) stents with no need for septal occluder. The other two patients had large RA-type SVASD who underwent closure using covered CP stents only in one patient and stents and device in the other one. An angiogram in the RUPV during balloon inflation in the SVC was done to ensure that the RUPV drains back to the left atrium. The covered CP stent was mounted and hand crimped onto Z-Med™ or BIB-balloon catheters and deployed in the desired location under transesophageal echocardiography guidance. RESULTS: The two patients with SVC-type SVASD underwent successful closure using two overlapping covered CP stents implanted in the SVC, thus creating total septation between the SVC and the RUPV. The RA-type SVASD patients underwent closure using two overlapping covered CP stents. One with mild to moderate residual shunt that completely disappeared at 12 months follow-up after implantation of a second 45 mm CP stent. A significant residual shunt in the second patient was closed successfully using a PFO device. CONCLUSION: Transcatheter closure of SVASD through SVC stent insertion with or without subsequent device implantation is feasible and effective.

Initial experiences with a novel biodegradable device for percutaneous closure of atrial septal defects: From preclinical study to first-in-human experience.

OBJECTIVE: To evaluate the feasibility, safety, and effectiveness of a novel, absorbable atrial septal defect (ASD) closure device made of poly-l-lactic acid (PLLA) in a swine model of ASD and for the first time in humans. METHODS: A preclinical safety study was conducted using a swine model of ASD. In a clinical setting, five pediatric patients underwent ASD closure with the PLLA device with fluoroscopic and transthoracic echocardiography guidance. The procedural results and clinical outcomes at 1 day, 30 days, 3 months, and 6 months after closure were analyzed. RESULTS: The 24- and 36-month follow-up results of the preclinical study demonstrated that the PLLA device exhibited good endothelialization and degradability in the swine model. In the clinical study, successful device implantation was achieved in all five patients (median age, 3.6 years; range, 3.1-6.5 years). The mean defect size was (13.6 ± 2.7) mm. Follow-up at 30 days, 3 months, and 6 months was completed in all five cases. The complete defect closure rates with no residual shunt at 30 days, 3 months, and 6 months follow-up were 60% (3/5), 80% (4/5), and 80% (4/5), respectively. No device dislodgement, significant aortic valve or mitral valve regurgitation, new onset cardiac arrhythmia, or other adverse events were reported. CONCLUSION: The study results demonstrated that it is feasible to implant the PLLA device for closure of small to medium sized ASDs without significant residual shunts or severe adverse events in humans. The PLLA device exhibited good endothelialization and degradability in the swine model at 24 and 36 months. Further studies to evaluate long-term safety and effectiveness with the device in a large cohort of patients are warranted.

Unusual interatrial fistula discovered during device closure of an atrial septal defect.

Atrial septal defect (ASD) closure is a common reason for referral to the cardiac catheterization laboratory. We report a case in which a relatively large Qp:Qs of 1.85:1 was demonstrated in the face of a small secundum ASD. This led to further investigation, ultimately leading to the discovery of an unusual atrial fistula. Rare cases of interatrial tunnels have been described in the literature, however, this is a unique case of a left atrial appendage to right atrial appendage fistula in the setting of a right juxtaposed left atrial appendage.

Transseptal access for left heart structural interventions in the setting of prior atrial septal defect closure.

A transseptal puncture is critical for "left-sided" structural heart interventions. Procedures such as transcatheter edge-to-edge repair (MitraClip) and left atrial appendage (LAA) closure (Watchman) require precise puncture of the interatrial septum (IAS), and the presence of a prior atrial septal defect (ASD) closure device poses a challenge. We aim to present a successfully completed case of MitraClip and Watchman in the presence of ASD closure device in two different patients. A review of the literature will be reported, and pertinent clinical and technical considerations will be discussed in depth to achieve procedural success. In summary, transseptal puncture for left heart structural interventions is feasible in the presence of a prior ASD/patent foramen ovale closure device. A detailed understanding of the anatomical considerations as well as the use of multimodality imaging to evaluate the IAS will aid in improving procedural success rates.

Impact of Right Ventricular Dilatation in Patients with Atrial Septal Defect.

OBJECTIVE: The aim of this study was to examine the relationship between right ventricular (RV) volume and exercise capacity in adult patients with atrial septal defect (ASD) and to determine the degree of RV dilatation for transcatheter ASD closure. BACKGROUND: RV dilatation is an indication of transcatheter ASD closure; however, few studies have reported the clinical significance of RV dilatation. METHODS: We enrolled 82 consecutive patients (mean age, 49 ± 18 years; female, 68%) who underwent cardiac magnetic resonance imaging and symptom-limited cardiopulmonary exercise test before ASD closure. The relationship between RV volume and peak oxygen uptake (VO2) was evaluated. RESULTS: The mean RV end-diastolic volume index was 108 ± 27 ml/m2 (range, 46 to 180 ml/m2). The mean peak VO2 was 24 ± 7 ml/min/kg (range, 14 to 48 ml/min/kg), and the mean predicted peak VO2 was 90 ± 23%. There were significant negative relationships of RV end-diastolic volume index with peak VO2 (r = -0.28, p < 0.01) and predicted peak VO2 (r = -0.29, p < 0.01). The cutoff value of RV end-diastolic volume index <80% of predicted peak VO2 was 120 ml/m2, with the sensitivity of 49% and the specificity of 89%. CONCLUSIONS: There was a relationship between RV dilatation and exercise capacity in adult patients with ASD. RV end-diastolic volume index ≥120 ml/m2 was related to the reduction in peak VO2. This criterion of RV dilatation may be valuable for the indication of transcatheter ASD closure.