Percutaneous heart valves demonstrating long-term durability: A case series of Melody valves in the pulmonary position lasting up to 19 years.

It is uncertain how long catheter delivered percutaneous heart valves may last. In congenital cardiology, stenosis and regurgitation of right ventricular to pulmonary artery conduits and valves is common, leading to repeated operations for young patients with concomitant mortality and morbidity. It has also been unclear whether percutaneous pulmonary valves last as long as surgical pulmonary valves. When the current generation of the percutaneous pulmonary valve was first implanted in the United Kingdom from 2003, randomized trials were initially not performed, decided on a case-by-case basis in congenital cardiology, nor long-term registries kept. We describe three cases where such percutaneous heart valves have lasted up to 19 years. All valves were working without significant stenosis and minor degrees of regurgitation on long-term echocardiographic follow-up, patients being asymptomatic. This demonstrates that percutaneous pulmonary valves can achieve long-term durability and may prevent the need for otherwise high-risk surgery in congenital cardiac patients.

A cell-autonomous role of Cited2 in controlling myocardial and coronary vascular development.

AIMS: Myocardial development is dependent on concomitant growth of cardiomyocytes and a supporting vascular network. The coupling of myocardial and coronary vascular development is partly mediated by vascular endothelial growth factor (VEGFA) signalling and additional unknown mechanisms. We examined the cardiomyocyte specific role of the transcriptional co-activator Cited2 on myocardial microstructure and vessel growth, in relation to Vegfa expression. METHODS AND RESULTS: A cardiomyocyte-specific knockout of mouse Cited2 (Cited2(Nkx)) was analysed using magnetic resonance imaging and histology. Ventricular septal defects and significant compact layer thinning (P < 0.02 at right ventricular apex, P < 0.009 at the left ventricular apex in Cited2(Nkx) vs. controls, n = 11 vs. n = 7, respectively) were found. This was associated with a significant decrease in the number of capillaries to larger vessels (ratio 1.56 ± 0.56 vs. 3.25 ± 1.63, P = 2.7 × 10(-6) Cited2(Nkx) vs. controls, n = 11 vs. n = 7, respectively) concomitant with a 1.5-fold reduction in Vegfa expression (P < 0.02, Cited2(Nkx) vs. controls, n = 12 vs. n = 12, respectively). CITED2 was subsequently found at the Vegfa promoter in mouse embryonic hearts using chromatin immunoprecipitation, and moreover found to stimulate human VEGFA promoter activity in cooperation with TFAP2 transcription factors in transient transfection assays. There was no change in the myocardial expression of the left-right patterning gene Pitx2c, a previously known target of CITED2. CONCLUSIONS: This study delineates a novel cell-autonomous role of Cited2 in regulating VEGFA transcription and the development of myocardium and coronary vasculature in the mouse. We suggest that coupling of myocardial and coronary growth in the developing heart may occur in part through a Cited2→Vegfa pathway.

Effect of Sodium-Glucose Cotransporter 2 Inhibitors in Adults With Congenital Heart Disease.

BACKGROUND: Heart failure (HF) is the principal cause of morbidity and mortality in adults with congenital heart disease (ACHD). Robust evidence-based treatment options are lacking. OBJECTIVES: This study aims to evaluate the safety, tolerability, and short-term HF-related effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in a real-world ACHD population. METHODS: All patients with ACHD treated with SGLT2i in 4 European ACHD centers were included in this retrospective study. Data were collected from 1 year before starting SGLT2i to the most recent follow-up. Data on side effects, discontinuation, mortality, and hospitalizations were collected. RESULTS: In total, 174 patients with ACHD were treated with SGLT2i from April 2016 to July 2023. The mean age was 48.7 ± 15.3 years, 72 (41.4%) were female, and 29 (16.7%) had type 2 diabetes mellitus. Ten (5.7%) patients had mild, 75 (43.1%) moderate, and 89 (51.1%) severe congenital heart disease. HF was the most frequent starting indication (n = 162, 93.1%), followed by type 2 diabetes (n = 11, 6.3%) and chronic kidney disease (n = 1, 0.6%). At median follow-up of 7.7 months (Q1-Q3: 3.9-13.2 months), 18 patients (10.3%) reported side effects, 12 (6.9%) permanently discontinued SGLT2i, and 4 (2.3%) died of SGLT2i-unrelated causes. A significant reduction in the HF hospitalization rate was observed from 6 months before to 6 months after starting SGLT2i (relative rate = 0.30; 95% CI: 0.14-0.62; P = 0.001). CONCLUSIONS: SGLT2i generally seem safe, well-tolerated, and potentially beneficial in patients with ACHD. SGLT2i was associated with a 3-fold reduction in the 6-month HF hospitalization rate. These results warrant prospective randomized investigation of the potential benefits of SGLT2i for patients with ACHD.

Initial use of the new GORE(®) septal occluder in patent foramen ovale closure: implantation and preliminary results.

BACKGROUND: A number of devices are available for percutaneous closure of a clinically significant patent foramen ovale (PFO). The new GORE(®) septal occluder (GSO) is a nonself-centering device consisting of an expanded polytetrafluoroethylene tube supported by a frame of nitinol wire conforming into a double disk. This study reports the first clinical GSO implantation experience. METHODS: GSO implantation in 20 consecutive patients is reported. Inclusion criteria were all patients referred with a significant PFO implicated in paradoxical embolism or transient right to left shunting causing desaturation. Procedures were performed under local anaesthesia and intracardiac echocardiography (ICE) in addition to fluoroscopy. Procedural data, acute and early closure rates were examined. RESULTS: All patients underwent successful day-case device implantation. Eleven patients had previous stroke, five had transient ischemic attacks, two had a history suspicious of PFO-related desaturation, and two had a history suspicious of PFO-related peripheral thromboembolism. Acute closure rates on IVC injection bubble testing were 100% at implant and 100% (14/14) at 1 month. Average PFO balloon size was 8.0 ± 3.6(range 2.0-16.7) mm, mean fluoroscopic implantation time 3.0 ± 1.7(range 0.7-6.3) min, radiation dose 283 ± 340 (range 6-1,431) µGym(2), and total procedural time 34.8 ± 8.0 (range 22-53) min. 5 × 20 mm(2), 7 × 25 m(2), 8 × 30 mm(2) GSO devices were implanted, aiming for device size at least twice balloon PFO size. Cases included aneurysmal septums with up to 30 mm deviation and tunnels up to 12 mm long. Removal and repositioning of two devices was performed on two occasions after uncertainty about device locking. At 1 month follow-up, two patients had brief self-terminating episodes of suspected atrial fibrillation, all had normal resting ECGs. No thromboembolic/neurological events were reported. CONCLUSIONS: The GSO can be implanted under local anaesthesia and ICE with low procedural and fluoroscopy times with high procedural success as a day case. No residual shunts were seen. This initial experience suggests that it is a safe and effective device for PFO closure.

Telescopic catheter-in-long sheath and parallel to a stiff guide wire technique for complex pulmonary artery anatomy.

Selective catheterization and procedures in pulmonary arteries may be very challenging. We developed a technique in which an extra-stiff guide wire was placed in a pulmonary artery. Across it a long sheath was placed proximally or controlateral to the lesion to be treated. An angiographic catheter was then placed parallel to the guide wire in a telescopic way within the long sheath. This system facilitated greater stability, allowing fine tuning of catheter position to reach and treat the target lesion. Here, we present five cases in whom this technique was used; a patient with multiple arteriovenous fistulas in a difficult to reach area and four subjects with complex pulmonary artery stenoses.

Over-the-wire-technique device implantation.

INTRODUCTION: Transcatheter closure of cardiac defects is a mainstay of treatment in congenital and structural heart disease. Occasionally, the devices used are useful in nonstandard or difficult positions but device embolization and malposition can be complicating factors necessitating percutaneous retrieval or emergency surgery. We describe a new "over-the-wire" technique that allows guided safe deployment and easy retrievability if required. METHODS: We describe 5 cases in which Amplatzer devices were delivered over a wire in challenging anatomy in high-risk patients. These cases included baffle leak in complex congenital heart disease, paravalvular leak, a large patent ductus arteriosus, and complex ventricular septal defects. In each case, the device was punctured close to the release mechanism and a guidewire fed through it, the device and guidewire then being loaded into the appropriate delivery system. The procedure is described in each case, illustrating the use of the technique. CONCLUSION: We describe a novel over-the-wire technique that is useful in deployment of Amplatzer devices in difficult and challenging anatomy, allowing careful controlled delivery and easy retrieval. This will help minimize procedural patient risk in complex cases.

Protein-losing enteropathy resolved by percutaneous intervention.

The extracardiac total cavopulmonary connection is the final stage of palliation of hearts with single-ventricle physiology. Protein-losing enteropathy (PLE) and plastic bronchitis are catastrophic sequale that may occur in patients with the total cavopulmonary connection and may complicate the early and long-term follow-up. Here we report on the successful treatment of a 16-year boy affected by PLE by percutaneous closure of a persistent anterograde pulmonary blood flow by using an 8-mm Amplatzer VSD Occluder.

Aortic coarctation complicated by wall aneurysm: the role of covered stents.

OBJECTIVES: To evaluate the management of aneurysms associated with aortic coarctation by covered stent deployment. BACKGROUND: Aortic aneurysm formation complicating aortic coarctation carries a risk of rupture with high mortality rate. Surgical repair has a significant mortality and may be associated with central nervous system injury, including paraplegia. Transcatheter intervention alternatively carries a risk of aneurysmal rupture. METHODS: Between July 2004 and September 2009, 140 consecutive patients underwent percutaneous stent implantation to treat aortic coarctation. Eleven (7.9%) patients had coarctation associated with aortic wall aneurysm: three with native coarctation with wall aneurysm, three with previous surgical coarctation repair, three with previous balloon angioplasty, and two with previous bare stent implantation. The e-PTFE-covered 8Zig Cheatham-Platinum stents were used to treat all 11 patients. RESULTS: Median age at procedure was 13 years (range, 6-66 years). Successful device deployment was achieved in all patients. Systolic pressure gradient reduced significantly from a median baseline of 30 mm Hg (range, 25-50 mm Hg) to a postprocedural median of 5 mm Hg (range, 0-20 mm Hg) (P < 0.01). Aortic diameter increased from a median value of 6 mm (range, 0.5-11 mm) to a median value of 12 mm (range, 10-22 mm) (P < 0.001). No early complications occurred, with successful relief of stenoses and complete sealing of all aneurysms. Median follow-up was 50 months (range, 16-61 months). Redilatation was required in four patients (one patient with intrastent restenosis secondary to significant endothelial growth, whereas the other three patients showed restenosis secondary to somatic growth). Redilatation with a larger balloon was performed without complication in all cases. CONCLUSIONS: Our data show that covered stents are a safe and effective treatment with low risk of complications for the treatment of coarctation associated with aortic wall aneurysm.

Intracardiac echocardiography off piste? Closure of the left atrial appendage using ICE and local anesthesia.

Left atrial appendage (LAA) occlusion is increasingly accepted to reduce the risk of stroke in patients with atrial arrhythmia who are unsuitable for routine anticoagulation. It is generally performed under general anesthesia, guided by transoesophageal echocardiography with accurate imaging being essential for correct deployment of the device. We present a case where LAA occlusion was done under local anesthesia in a high-anesthetic risk patient, using novel placement of an intracardiac echo probe via a Mullins sheath in the right ventricular outflow tract and pulmonary artery. This allowed accurate visualization of device deployment in the LAA. This technique may increase the spectrum of patients who may benefit from the procedure and decrease procedure time, fluoroscopy, and procedure-related morbidity.

Epiblastic Cited2 deficiency results in cardiac phenotypic heterogeneity and provides a mechanism for haploinsufficiency.

AIMS: Deletion of the transcription factor Cited2 causes penetrant and phenotypically heterogenous cardiovascular and laterality defects and adrenal agenesis. Heterozygous human CITED2 mutation is associated with congenital heart disease, suggesting haploinsufficiency. Cited2 functions partly via a Nodal-->Pitx2c pathway controlling left-right patterning. In this present study we investigated the primary site of Cited2 function and mechanisms of haploinsufficiency. METHODS AND RESULTS: A Cited2 conditional allele enabled its deletion in particular cell lineages in mouse development. A lacZ reporter cassette allowed indication of deletion. Congenic Cited2 heterozygous mice were used to investigate haploinsufficiency. Embryos were examined by magnetic resonance imaging, by sectioning and by quantitative real-time polymerase chain reaction (qRT-PCR). Epiblast-specific deletion of Cited2 using Sox2Cre recapitulated penetrant and phenotypically heterogenous cardiovascular and laterality defects. Neural crest-specific deletion using Wnt1Cre affected cranial ganglia but not cardiac development. Mesodermal deletion with Mesp1Cre resulted in low penetrance of septal defect. Mesodermal deletion with T-Cre resulted in adrenal agenesis, but infrequent cardiac septal and laterality defects. beta-Galatactosidase staining and qRT-PCR demonstrated the efficiency and location of Cited2 deletion. Murine Cited2 heterozygosity is itself associated with cardiac malformation, with three of 45 embryos showing ventricular septal defect. Cited2 gene expression in E13.5 hearts was reduced 2.13-fold in Cited2(+/-) compared with wild-type (P = 2.62 x 10(-6)). The Cited2 target gene Pitx2c was reduced 1.5-fold in Cited2(+/-) (P = 0.038) hearts compared with wild-type, and reduced 4.9-fold in Cited2(-/-) hearts (P = 0.00031). Pitx2c levels were reduced two-fold (P = 0.009) in Cited2(+/-) embryos, in comparison with wild-type. Cited2 and Pitx2c expression were strongly correlated in wild-type and Cited2(+/-) hearts (Pearson rank correlation = 0.68, P = 0.0009). Cited2 expression was reduced 7474-fold in Sox2Cre deleted hearts compared with controls (P = 0.00017) and Pitx2c was reduced 3.1-fold (P = 0.013). Deletion of Cited2 with Mesp1Cre resulted in a 130-fold reduction in cardiac Cited2 expression compared with control (P = 0.0002), but Pitx2c expression was not affected. CONCLUSION: These results indicate that phenotypically heterogenous and penetrant cardiac malformations in Cited2 deficiency arise from a primary requirement in epiblast derivatives for left-right patterning, with a secondary cell-autonomous role in the mesoderm. Cardiac malformation associated with Cited2 haploinsufficiency may occur by reducing expression of key Cited2 targets such as Pitx2c.

Echocardiographic Screening for Pulmonary Hypertension in Congenital Heart Disease: JACC Review Topic of the Week.

Echocardiography is the mainstay in screening for pulmonary hypertension (PH). International guidelines suggest echocardiographic parameters for suspecting PH, but these may not apply to many adults with congenital heart disease (ACHD). PH is relatively common in ACHD patients and can significantly affect their exercise capacity, quality of life, and prognosis. Identification of patients who have developed PH and who may benefit from further investigations (including cardiac catheterization) and treatment is thus extremely important. A systematic review and survey of experts from the United Kingdom and Ireland were performed to assess current knowledge and practice on echocardiographic screening for PH in ACHD. This paper presents the findings of the review and expert statements on the optimal approaches when using echocardiography to assess ACHD patients for PH, with particular focus on major subgroups: patients with right ventricular outflow tract obstruction, patients with systemic right ventricles, patients with unrepaired univentricular circulation, and patients with tetralogy of Fallot with pulmonary atresia.

Occlutech percutaneous patent foramen ovale closure: Safety and efficacy registry (OPPOSE).

INTRODUCTION: Safety and efficacy data on patent foramen ovale (PFO) closure with the Occlutech Figulla Flex II device are lacking. We undertook a fully monitored prospective Registry on PFO closure using this device. METHODS: 100 patients undergoing PFO closure were enrolled into the OPPOSE Registry at 6 UK centres. The primary endpoint was PFO closure (grade 0 or 1 shunt) at 6-month BCTTE assessed by Corelab. Secondary endpoints included implantation success, complications, and atrial fibrillation during follow-up. RESULTS: 100 patients aged 43.8±11.5years, 53% male, were recruited. Indications for PFO closure included stroke (56%), TIA (29%) systemic embolism (4%) and MI (3%). Closure was undertaken under GA (44%) or LA (56%), with TOE (45%), ICE (31%), no imaging (20%) or TTE (3%). Balloon sizing was used in 98% of cases and showed a tunnel length of 7.3±3.6mm, primum-secundum separation of 7.0±2.9mm and basal inlet width of 8.5±3.5mm. Implantation was successful in all cases using 18mm (9%), 25mm (80%), 30mm (10%) and 35mm (1%) devices. 5 patients were lost to follow-up. 92 patients underwent six-month BCTTE. The primary endpoint of PFO closure (grade 0 or 1 shunt) at six months was 79.3%. One patient developed major bleeding (BARC 3b), one patient required vascular surgery, and in one patient device embolization was noted at six months and a larger device implanted. There was one case of new atrial fibrillation. CONCLUSIONS: This first prospective monitored data for the Occlutech Figulla Flex II device demonstrates good safety and efficacy data at implant and six-month follow-up.

Initial experience with the Amplatzer Vascular Plug IV in congenital heart disease: coronary artery fistula and aortopulmonary collateral artery embolization.

BACKGROUND: A number of percutaneous devices are available to embolize anomalous vessels in congenital heart disease. We report our initial single-center experience with the new Amplatzer Vascular Plug IV (AVP IV) in congenital heart disease to embolize a coronary artery fistula and aortopulmonary collateral arteries in 4 cases. METHODS: From August 2009 until April 2010, 7 AVP IV devices were deployed in 4 patients, age range 5 months to 9 years, weight 3.5-27.7 kg. One patient had a large coronary artery fistula, the others had anomalous aortopulmonary collaterals; 2 patients had tetralogy of Fallot with pulmonary atresia, with the other having dextrocardia, anomalous pulmonary venous drainage and pulmonary atresia. RESULTS: In all 4 patients, vessels intended to be closed with the AVP IV were closed successfully with minimal residual shunting and no device failures. Deployed devices ranged from 4-8 mm in diameter. One patient had 4 devices, closing large branching infradiaphragmatic aortopulmonary collaterals. The other 3 patients had single devices. Complete vessel embolization was seen with no device embolization or implantation complication. CONCLUSION: This preliminary experience illustrates the utility of the AVP IV in congenital heart disease, occluding a coronary artery fistula and aorto-pulmonary collaterals, with devices between 4 mm and 8 mm in diameter, demonstrating its safety and effectiveness. It is particularly useful in embolizing difficult-to-reach large, tortuous vessels with a small-sized catheter in a single procedure. Longer-term follow up in a larger cohort of patients will be required to establish long-term efficacy and device safety.

Managing adults with congenital heart disease in the catheterization laboratory: state of the art.

There has been a rapid growth in interventional cardiology techniques to treat adults with congenital heart disease, mirroring the rise of interventional cardiology as a cardiology subspecialty and the increasing population of adults with congenital abnormalities. Starting with neonatal balloon atrial septostomy for transposition of the great arteries in the 1960s, improving and changing percutaneous interventional techniques have increasingly replaced surgery as a treatment option in several congenital heart diseases. Many pediatric cardiac patients now survive to adulthood following early surgery, perhaps making additional surgery higher risk, and percutaneous procedures offer an alternative approach, although with a different inherent set of risks and benefits in terms of morbidity and mortality. Adult congenital heart disease patients offer distinct challenges such as unusual anatomy and demands such as pregnancy and exercise tolerability not found in conventional pediatric or traditional adult interventional patients. This article reviews current indications for adult congenital heart disease intervention and best practice, detailing the patient spectrum commonly treated, devices used and emerging treatments.

The relationship of systemic right ventricular function to ECG parameters and NT-proBNP levels in adults with transposition of the great arteries late after Senning or Mustard surgery.

AIMS: Heart failure is common late after Senning or Mustard palliation of transposition of the great arteries (TGA). Although cardiac magnetic resonance (CMR) is the gold standard for evaluating systemic right ventricular performance, additional information regarding heart failure status might be gleaned from the surface ECG and circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. The interrelationships between these heart failure markers were examined in adults late after Mustard and Senning surgery. METHODS: Thirty-five consecutive adults with Senning or Mustard repair of TGA attending a dedicated congenital heart failure clinic were studied. Assessment included symptom assessment, venous blood sampling for measurement of circulating NT-proBNP levels, surface 12-lead ECG and CMR for the assessment of right ventricular systolic function and determination of indexed right ventricular volumes. RESULTS: Mean age was 29 ± 6.5 years, 54% had undergone Mustard surgery. Compared with those with uncomplicated surgery, patients with complex surgical history had higher NT-proBNP levels (55 ± 26 vs 20 ± 35 pmol/l; p=0.002) and longer QRS duration (116 ± 28 ms vs 89 ± 11 ms; p=0.0004) while showing no difference in New York Heart Association class and right ventricular function. There was a significant relationship between diastolic and systolic right ventricular volumes and both NT-proBNP levels (r=0.43, p=0.01; r=0.53, p=0.001, respectively) and QRS duration (r=0.47, p=0.004; r=0.53, p=0.001, respectively). CONCLUSIONS: Circulating NT-proBNP levels and several surface ECG parameters constitute safe, cost-effective and widely available surrogate markers of systemic right ventricular function and provide additional information on heart failure status. Both measures hold promise as prognostic markers and their association with long-term outcome should be determined.

Molecular mechanisms controlling the coupled development of myocardium and coronary vasculature.

Cardiac failure affects 1.5% of the adult population and is predominantly caused by myocardial dysfunction secondary to coronary vascular insufficiency. Current therapeutic strategies improve prognosis only modestly, as the primary cause -- loss of normally functioning cardiac myocytes -- is not being corrected. Adult cardiac myocytes are unable to divide and regenerate to any significant extent following injury. New cardiac myocytes are, however, created during embryogenesis from progenitor cells and then by cell division from existing cardiac myocytes. This process is intimately linked to the development of coronary vasculature from progenitors originating in the endothelium, the proepicardial organ and neural crest. In this review, we systematically evaluate approx. 90 mouse mutations that impair heart muscle growth during development. These studies provide genetic evidence for interactions between myocytes, endothelium and cells derived from the proepicardial organ and the neural crest that co-ordinate myocardial and coronary vascular development. Conditional knockout and transgenic rescue experiments indicate that Vegfa, Bmpr1a (ALK3), Fgfr1/2, Mapk14 (p38), Hand1, Hand2, Gata4, Zfpm2 (FOG2), Srf and Txnrd2 in cardiac myocytes, Rxra and Wt1 in the proepicardial organ, EfnB2, Tek, Mapk7, Pten, Nf1 and Casp8 in the endothelium, and Bmpr1a and Pax3 in neural crest cells are key molecules controlling myocardial development. Coupling of myocardial and coronary development is mediated by BMP (bone morphogenetic protein), FGF (fibroblast growth factor) and VEGFA (vascular endothelial growth factor A) signalling, and also probably involves hypoxia. Pharmacological targeting of these molecules and pathways could, in principle, be used to recreate the embryonic state and achieve coupled myocardial and coronary vascular regeneration in failing hearts.