Surgery for complications of trans-catheter closure of atrial septal defects: a multi-institutional study from the European Congenital Heart Surgeons Association

This study aims to analyse the collective experience of participating European Congenital Heart Surgeons Association centres in the surgical management of complications resulting from trans-catheter closure of atrial septal defects (ASDs).

Approaching atrial septal defects in pulmonary hypertension

Atrial septal defects (ASDs) are one of the most frequent congenital cardiac malformations, accounting for about 8-10% of all congenital heart defects. The prevalence of pulmonary arterial hypertension (PAH) in adults with an ASD is 8-10%. Different clinical PAH scenarios can be encountered. At one end of the spectrum are adults with no or only mild pulmonary vascular disease and a large shunt. These are patients who can safely undergo shunt closure. In the elderly, mild residual pulmonary hypertension after shunt closure is the rule. At the other end of the spectrum are adults with severe, irreversible pulmonary vascular disease, shunt reversal and chronic cyanosis, that is, Eisenmenger syndrome. These are patients who need to be managed medically. The challenge is to properly classify ASD patients with PAH falling in between the two ends of the spectrum as the ones with advanced, but reversible pulmonary vascular disease amenable to repair, versus the ones with progressive pulmonary vascular disease not responding to shunt closure. There are concerns that adults with progressive pulmonary vascular disease have worse outcomes after shunt closure than patients not undergoing shunt closure. Due to the correlation of pulmonary vascular changes and pulmonary hemodynamics, cardiac catheterization is used in the decision-making process. It is important to consider the hemodynamic data in the context of the clinical picture, the defect anatomy and further noninvasive tests when evaluating the option of shunt closure in these patients.

Safety, feasibility, and long-term results of percutaneous closure of atrial septal defects using the Amplatzer septal occluder without periprocedural echocardiography.

OBJECTIVES We sought to assess the safety and efficacy of percutaneous closure of atrial septal defects (ASDs) under fluoroscopic guidance only, without periprocedural echocardiographic guidance. BACKGROUND Percutaneous closure of ASDs is usually performed using simultaneous fluoroscopic and transthoracic, transesophageal (TEE), or intracardiac echocardiographic (ICE) guidance. However, TEE requires deep sedation or general anesthesia, which considerably lengthens the procedure. TEE and ICE increase costs. METHODS Between 1997 and 2008, a total of 217 consecutive patients (age, 38 ± 22 years; 155 females and 62 males), of whom 44 were children ≤16 years, underwent percutaneous ASD closure with an Amplatzer ASD occluder (AASDO). TEE guidance and general anesthesia were restricted to the children, while devices were implanted under fluoroscopic guidance only in the adults. For comparison of technical safety and feasibility of the procedure without echocardiographic guidance, the children served as a control group. RESULTS The implantation procedure was successful in all but 3 patients (1 child and 2 adults; 1.4%). Mean device size was 23 ± 8 mm (range, 4-40 mm). There was 1 postprocedural complication (0.5%; transient perimyocarditis in an adult patient). At last echocardiographic follow-up, 13 ± 23 months after the procedure, 90% of patients had no residual shunt, whereas a minimal, moderate, or large shunt persisted in 7%, 1%, and 2%, respectively. Four adult patients (2%) underwent implantation of a second device for a residual shunt. During a mean follow-up period of 3 ± 2 years, 2 deaths and 1 ischemic stroke occurred. CONCLUSION According to these results, percutaneous ASD closure using the AASDO without periprocedural echocardiographic guidance seems safe and feasible.

Patent foramen ovale and ventricular septal defect closure

Despite the growing recognition of the patent foramen ovale (PFO), particularly when associated with an atrial septal aneurysm, as risk factor for several disease manifestations (above all paradoxical embolism), the optimal treatment strategy for symptomatic patients remains controversial. Percutaneous PFO closure is a minimally invasive procedure which can be performed with high success and low morbidity. For secondary prevention of recurrent embolic events, it appears to be clinically at least as effective as oral anticoagulation. Ventricular septal defects (VSDs) are the most common congenital heart defects. Percutaneous VSD closure is more intricate than PFO closure. It is associated with a significant risk of both peri-interventional and mid-term complications. In suitable patients with congenital VSD, device closure may well be the preferred treatment both for muscular or perimembranous VSDs and for residual defects after surgical VSD closure. The risk of complete atrioventricular conduction block remains a concern in the perimembranous group. The history, technique and clinical role of percutaneous PFO and VSD closure are discussed, with emphasis on current problems and future developments.

Angiotensinergic and noradrenergic neurons in the rat and human heart

Although the physiological and pharmacological evidences suggest a role for angiotensin II (Ang II) with the mammalian heart, the source and precise location of Ang II are unknown. To visualize and quantitate Ang II in atria, ventricular walls and interventricular septum of the rat and human heart and to explore the feasibility of local Ang II production and function, we investigated by different methods the expression of proteins involved in the generation and function of Ang II. We found mRNA of angiotensinogen (Ang-N), of angiotensin converting enzyme, of the angiotensin type receptors AT(1A) and AT(2) (AT(1B) not detected) as well as of cathepsin D in any part of the hearts. No renin mRNA was traceable. Ang-N mRNA was visualized by in situ hybridization in atrial ganglial neurons. Ang II and dopamine- -hydroxylase (D H) were either colocalized inside the same neuronal cell or the neurons were specialized for Ang II or D H. Within these neurons, the vesicular acetylcholine transporter (VAChT) was neither colocalized with Ang II nor D H, but VAChT-staining was found with synapses en passant encircle these neuronal cells. The fibers containing Ang II exhibited with blood vessels and with cardiomyocytes supposedly angiotensinergic synapses en passant. In rat heart, right atrial median Ang II concentration appeared higher than septal and ventricular Ang II. The distinct colocalization of neuronal Ang II with D H in the heart may indicate that Ang II participates together with norepinephrine in the regulation of cardiac functions: Produced as a cardiac neurotransmitter Ang II may have inotropic, chronotropic or dromotropic effects in atria and ventricles and contributes to blood pressure regulation.

Iatrogenic atrial septal defect, erosion of the septum primum after device closure of a patent foramen ovale as a new medical entity

Iatrogenic atrial septal defects are described in 2 patients. They occurred after implantation of Amplatzer occluders to close a patent foramen ovale. While device erosions to the extra-atrial space have been described, erosion induced atrial septal defects are a new medical entity. They may be fairly common in the situation of an atrial septal aneurysm whipping the rim of the device incessantly. They are clinically silent and benign and require echocardiography for detection. A second device solved the problem in the cases described.

Paracellin-1 gene mutation with multiple congenital abnormalities

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is an autosomal recessive renal tubular disorder characterized by renal magnesium wasting, hypercalciuria, advanced nephrocalcinosis and progressive renal failure. Mutations in the paracellin-1 (CLDN16) gene have been defined as the underlying genetic defect. The tubular disorders and progression in renal failure are usually resistant to magnesium substitution and hydrochlorothiazide therapy, but hypomagnesemia may improve with advanced renal insufficiency. We present a patient with a homozygous truncating CLDN16 gene mutation (W237X) who had early onset of renal insufficiency despite early diagnosis at 2 months. He also had additional abnormalities including horseshoe kidney, neonatal teeth, atypical face, cardiac abnormalities including coarctation of the aorta associated with atrial and ventricular septal defects, umbilical hernia and hypertrichosis. To the best of our knowledge, this is the youngest case diagnosed as familial hypomagnesemia with hypercalciuria and nephrocalcinosis and the first case having such additional congenital abnormalities independent of the disease itself.

Frequency of severe pulmonary hypertension complicating "isolated" atrial septal defect in infancy

Atrial septal defects (ASDs) are typically asymptomatic in infancy and early childhood, and elective defect closure is usually performed at ages of 4 to 6 years. Severe pulmonary hypertension (PH) complicating an ASD is seen in adulthood and has only occasionally been reported in small children. A retrospective study was undertaken to evaluate the incidence of severe PH complicating an isolated ASD and requiring early surgical correction. During a 10-year period (1996 to 2006), 355 pediatric patients underwent treatment for isolated ASDs either surgically or by catheter intervention at 2 tertiary referral centers. Two hundred ninety-seven patients had secundum ASDs, and 58 had primum ASDs with mild to moderate mitral regurgitation. Eight infants were found with isolated ASDs (6 with secundum ASDs and 2 with primum ASDs) associated with significant PH, accounting for 2.2% of all patients with ASDs at the centers. These 8 infants had invasively measured pulmonary artery pressures of 50% to 100% of systemic pressure. They were operated in the first year of life and had complicated postoperative courses requiring specific treatment for PH for up to 16 weeks postoperatively. The ultimate outcomes in all 8 infants were good, with persistent normalization of pulmonary pressures during midterm follow-up of up to 60 months (median 28). All other patients with ASDs had normal pulmonary pressures, and the mean age at defect closure was significantly older, at 6.2 years for secundum ASDs and 3.2 years for primum ASDs. In conclusion, ASDs were rarely associated with significant PH in infancy but then required early surgery and were associated with excellent midterm outcomes in these patients.

Endogenous α-calcitonin-gene-related peptide promotes exercise-induced, physiological heart hypertrophy in mice.

AIM It is unknown how the heart distinguishes various overloads, such as exercise or hypertension, causing either physiological or pathological hypertrophy. We hypothesize that alpha-calcitonin-gene-related peptide (αCGRP), known to be released from contracting skeletal muscles, is key at this remodelling. METHODS The hypertrophic effect of αCGRP was measured in vitro (cultured cardiac myocytes) and in vivo (magnetic resonance imaging) in mice. Exercise performance was assessed by determination of maximum oxygen consumption and time to exhaustion. Cardiac phenotype was defined by transcriptional analysis, cardiac histology and morphometry. Finally, we measured spontaneous activity, body fat content, blood volume, haemoglobin mass and skeletal muscle capillarization and fibre composition. RESULTS While αCGRP exposure yielded larger cultured cardiac myocytes, exercise-induced heart hypertrophy was completely abrogated by treatment with the peptide antagonist CGRP(8-37). Exercise performance was attenuated in αCGRP(-/-) mice or CGRP(8-37) treated wild-type mice but improved in animals with higher density of cardiac CGRP receptors (CLR-tg). Spontaneous activity, body fat content, blood volume, haemoglobin mass, muscle capillarization and fibre composition were unaffected, whereas heart index and ventricular myocyte volume were reduced in αCGRP(-/-) mice and elevated in CLR-tg. Transcriptional changes seen in αCGRP(-/-) (but not CLR-tg) hearts resembled maladaptive cardiac phenotype. CONCLUSIONS Alpha-calcitonin-gene-related peptide released by skeletal muscles during exercise is a hitherto unrecognized effector directing the strained heart into physiological instead of pathological adaptation. Thus, αCGRP agonists might be beneficial in heart failure patients.

Transcranial Doppler-guided deairing of a pediatric ventricular assist device: experience with twins

We report the intraoperative courses of 2 consecutive Berlin Heart Excor® Pediatric Ventricular Assist Device implantations, in which transcranial Doppler ultrasonography helped to detect macroscopically undetected residual air bubbles captured in the pump after air removal had been correctly performed according to manufacturer's specifications. Our experience with these cases suggests that a beat-to beat deairing maneuver guided by transcranial Doppler is a useful strategy for reducing cerebral exposure to perioperative gaseous microembolism.

Variable Na(v)1.5 protein expression from the wild-type allele correlates with the penetrance of cardiac conduction disease in the Scn5a(+/-) mouse model

BACKGROUND: Loss-of-function mutations in SCN5A, the gene encoding Na(v)1.5 Na+ channel, are associated with inherited cardiac conduction defects and Brugada syndrome, which both exhibit variable phenotypic penetrance of conduction defects. We investigated the mechanisms of this heterogeneity in a mouse model with heterozygous targeted disruption of Scn5a (Scn5a(+/-) mice) and compared our results to those obtained in patients with loss-of-function mutations in SCN5A. METHODOLOGY/PRINCIPAL FINDINGS: Based on ECG, 10-week-old Scn5a(+/-) mice were divided into 2 subgroups, one displaying severe ventricular conduction defects (QRS interval>18 ms) and one a mild phenotype (QRS< or = 18 ms; QRS in wild-type littermates: 10-18 ms). Phenotypic difference persisted with aging. At 10 weeks, the Na+ channel blocker ajmaline prolonged QRS interval similarly in both groups of Scn5a(+/-) mice. In contrast, in old mice (>53 weeks), ajmaline effect was larger in the severely affected subgroup. These data matched the clinical observations on patients with SCN5A loss-of-function mutations with either severe or mild conduction defects. Ventricular tachycardia developed in 5/10 old severely affected Scn5a(+/-) mice but not in mildly affected ones. Correspondingly, symptomatic SCN5A-mutated Brugada patients had more severe conduction defects than asymptomatic patients. Old severely affected Scn5a(+/-) mice but not mildly affected ones showed extensive cardiac fibrosis. Mildly affected Scn5a(+/-) mice had similar Na(v)1.5 mRNA but higher Na(v)1.5 protein expression, and moderately larger I(Na) current than severely affected Scn5a(+/-) mice. As a consequence, action potential upstroke velocity was more decreased in severely affected Scn5a(+/-) mice than in mildly affected ones. CONCLUSIONS: Scn5a(+/-) mice show similar phenotypic heterogeneity as SCN5A-mutated patients. In Scn5a(+/-) mice, phenotype severity correlates with wild-type Na(v)1.5 protein expression.

Initial clinical experience with the Coherex FlatStent™ and FlatStent™ EF PFO closure system for in-tunnel PFO closure: Results of the Coherex-EU study

OBJECTIVE The Coherex-EU Study evaluated the safety and efficacy of PFO closure utilizing novel in-tunnel PFO closure devices. BACKGROUND Transcatheter closure of patent foramen ovale (PFO) followed the development of transcatheter closure devices designed to patch atrial septal defects (ASDs). The Coherex FlatStent™ and FlatStent™ EF devices were designed specifically to treat PFO anatomy. METHODS A total of 95 patients with a clinical indication for PFO closure were enrolled in a prospective, multicenter first in man study at six clinical sites. Thirty-six patients received the first-generation FlatStent study device, and 57 patients received the second-generation FlatStent EF study device, which was modified based on clinical experience during the first 38 cases. Two patients enrolled to receive the first generation did not receive a device. RESULTS At 6 months post-procedure, 45% (17/38) of the intention-to-treat (ITT) cohort receiving the first-generation FlatStent device had complete closure, 26% (10/38) had a trivial residual shunt, and 29% (11/38) had a moderate to large residual shunt. In the ITT cohort receiving the second-generation FlatStent EF device, 76% (43/57) had complete closure, 12% (7/57) had a trivial shunt, and 12% had a moderate to large shunt. Five major adverse events occurred, all without sequelae. CONCLUSION This initial study of the Coherex FlatStent/FlatStent EF PFO Closure System demonstrated the potential for in-tunnel PFO closure. The in-tunnel Coherex FlatStent EF may offer an alternative to septal repair devices for PFO closure in appropriately selected patients; however, further investigation will be necessary to establish the best use of this device.

Percutaneous closure of a postinfarction ventricular septal defect and an iatrogenic left ventricular free-wall perforation using two Amplatzer muscular VSD occluders

A 83-year-old woman underwent percutaneous closure of postinfarction ventricular septal defect following anteroseptal myocardial infarction and percutaneous coronary intervention with stent implantation of the left anterior descending coronary artery. Postinfarction percutaneous ventricular septal defect closure was initially complicated by an iatrogenic left ventricular free-wall perforation. Both defects were closed using two Amplatzer muscular VSD occluders during the same session.