Use of the Prostacyclin Receptor Agonist Selexipag in Patients With Pulmonary Arterial Hypertension Associated With Eisenmenger Syndrome.

Eisenmenger syndrome is a multisystem disorder and the most severe form of pulmonary arterial hypertension in adult congenital heart disease. Pulmonary arterial hypertension represents a fatal disease, characterized by increased pulmonary vascular resistance, right heart failure, and death. Although therapeutic management has rapidly advanced in recent years, these patients were not included in randomized controlled trials for specific pulmonary arterial hypertension drugs, except for bosentan. However, in clinical practice we apply treatment strategies combining drugs targeting multiple pathobiological pathways. We present 3 patients with Eisenmenger syndrome and their improvement after starting treatment with selexipag, an oral selective IP prostacyclin receptor agonist.

Multiple myocardial bridges causing severe ischaemia in adolescent with pulmonary stenosis.

Myocardial bridges are often asymptomatic but may need therapy when causing ischaemia. They have rarely been reported in children or in association with CHD, where symptomatology may be mistakenly attributed to the CHD. We report a case of multiple myocardial bridges causing ischaemia in an adolescent with pulmonary stenosis and discuss management.

Cardiovascular imaging approach in pre and postoperative tetralogy of Fallot.

Advances in the medical and surgical management of Tetralogy of Fallot have led to marked increase of the number and age of survivors. Imaging in patients with Tetralogy of Fallot plays a crucial role in the diagnosis and follow up, and essentially guides management and intervention in this entity. This study systematically reviews the imaging modalities used in patients with Tetralogy of Fallot in the evaluation of preoperative and postoperative anatomic and hemodynamic lesions, as well as disease progression in this diagnosis. Various invasive and noninvasive imaging modalities, most commonly echocardiography and cardiovascular magnetic resonance, computed tomography and angiocardiography provide the imaging information required for diagnosis, management and follow up in Tetralogy of Fallot. The choice of the appropriate imaging tool or their combination is guided by the clinical question, the patient's clinical condition and contraindications as well as the strengths and weaknesses of each imaging modality. Tetralogy of Fallot is the most common complex congenital heart disease with long term survivors that need close follow up and complicated management, including multiple surgical and transcatheter interventions. Knowledge of the role and protocols of imaging in Tetralogy of Fallot is extremely important for the clinical as well as the imaging physician in order to optimize patients' management and long-term prognosis.

Ambulatory Intravenous Inotropic Support and or Levosimendan in Pediatric and Congenital Heart Failure: Safety, Survival, Improvement, or Transplantation.

End-stage heart failure (HF) frequently needs continuous inotropic support in hospital and has high morbidity and mortality in absence of heart transplantation. This study reports outcome, efficacy, and safety of continuous ambulatory inotropes (AI) and/or periodic levosimendan (LS) infusions in pediatric HF patients. The study included 27 patients, median age 9.4 (0.1-26.1) years, with severe HF (6 myocarditis, 13 dilated cardiomyopathy, 2 restrictive cardiomyopathy, 6 repaired congenital heart disease). Dobutamine and milrinone AI were administered in 21 patients through a permanent central catheter for median duration 1.0 (0.3-3.7) years. Additionally, 14 AI patients and the remaining 6 study patients received periodic LS infusions for median duration 1.1 (0.2-4.2) years. During median follow-up 2.1 (0.3-21.3) years, 4 patients died of worsening HF after 0.8-2.1 years AI, 6 patients underwent heart transplantation with only 3 survivors, while the rest remained stable out of the hospital with complications 4 line infections treated with antibiotics and 4 catheter reinsertions due to dislodgement. Severe pulmonary hypertension was reversed with AI in 2 patients, allowing successful heart-only transplantation. Therapy with AI was discontinued after 1.4-0.4 years in 6 improved myocarditis and 3 cardiomyopathy patients without deterioration. In conclusion, prolonged AI and/or LS infusions in HF are safe and beneficial even in small infants, allowing stabilization and reasonable social and family life out of the hospital. It may provide precious time for heart transplantation or myocardial remodeling, improvement, and possible discontinuation even after long periods of support.

Large single centre experience with the Cera™ and CeraFlex™ occluders for closure of interatrial communications: usefulness of the flexible rotation feature.

We present our experience with the Cera (CO) and the CeraFlex occluder (CFO) in transcatheter closure of interatrial communications (IAC). Between 2013 and 2016, 201 patients (75 males, 16 with patent foramen ovale), aged 27 ± 19 (5-75) years, underwent percutaneous closure of IAC using CO or CFO in our institution. After transoesophageal imaging, the procedure was aborted in 7 young paediatric (6-13 years old) patients (3 multiple holes, 3 too small septum, 1 leak with 38 mm occlusion balloon). The occluder was removed prior to release in 11 patients (5.7%), while occlusion was successful in 183 patients (94.3%) with 44 CO, 136 CFO, and 3 Cera multifenestrated occluders. There were no deaths, embolizations, or major complications. Small residual shunts were demonstrated in 8 patients immediately after implantation, 4 (8.5%) with CO and 4 (2.9%) with CFO, all disappearing after 3 months. Over 1.8 ± 1.7 year follow-up, all patients improved with 2 asymptomatic, transient pericardial effusions and 5 adults with transient supraventricular arrhythmias, treated medically for 6 months. IAC closure with CO and CFO proved safe with favourable success rates and few, nonserious complications. The CFO flexible rotation feature helped in conforming to various septal anatomies, minimising manoeuvres and possibly post-occlusion leaks.

The respiratory system in pediatric chronic heart disease.

Cardiovascular disease in the pediatric population closely affects the respiratory system inducing water retention in the lungs and pulmonary edema, airway compression by cardiovascular structures, restrictive pulmonary physiology as a result of hemodynamic changes and surgical repair, susceptibility to respiratory infections, development of pulmonary hypertension, thrombosis, or hemorrhage. Chronic heart failure and congenital heart disease are characterized by various respiratory manifestations and symptoms mimicking lung disease, which are frequently difficult to diagnose and treat. Pulmonary function is multiply affected in pediatric heart disease with mostly restrictive but also obstructive and diffusion abnormalities. Patients with Fontan circulation represent a separate group with slow, passive pulmonary blood flow and distinct pathophysiology with low cardiac output heart failure, restrictive lung pattern, increased thromboembolic complications and rare conditions such as protein losing enteropathy and plastic bronchitis. Distinguishing between cardiovascular and pulmonary symptoms may be challenging in the growing population of pediatric and adult survivors of congenital heart disease and understanding of the relationship of the two systems in heart disease is crucial for the optimal management of these patients.

Pulmonary vasodilator therapy in tetralogy of Fallot with pulmonary atresia and major aortopulmonary collaterals: case series and review of literature.

We present the use of pulmonary vasodilators in three adult patients with unrepaired tetralogy of Fallot, pulmonary atresia, aortopulmonary collaterals, and segmental pulmonary arterial hypertension. Patients improved by 1-2 NYHA classes with modest exercise-tolerance increase, and remained stable without side effects during 2.5, 10, and 14 years. Literature review revealed five studies with pulmonary vasodilators in heterogeneous, mostly repaired patient populations.

The Ross-Konno procedure as reoperative treatment in a young adult with congenital aortic stenosis.

Mechanical and biological prostheses are valid options when aortic valve replacement is necessary. The Ross procedure is also an alternative solution, especially for young patients. We describe the case of a young patient with congenital aortic stenosis and bicuspid aortic valve who presented with dyspnea on exertion. An open commissurotomy was performed, and within 8 months the patient developed recurrent symptoms of severe aortic stenosis. He underwent redo sternotomy and a Ross-Konno procedure with an uneventful recovery.

Radiation doses in paediatric interventional cardiology procedures.

The objective was to investigate paediatric doses in coronary angiography (CA) and percutaneous transluminal coronary angioplasty (PTCA) in the largest cardiac hospital in Greece. Forty procedures were carried out by two board-certified senior interventional cardiologists. Data collected were: patient weight, height, age, fluoroscopy time (FT), total number of images (N) and kerma-area product (KAP). Median (range) age was 7.5 y (17 d to 17 y). Median FT, N and KAP were 4 min, 655, 2.1 Gy cm2 for CA and 12.1 min, 1296, 14.7 Gy cm2 for PTCA (corresponding adult diagnostic reference levels (DRLs) are: 6.5 min, 700, 45 Gy cm2 for CA and 15.5 min, 1000 and 85 Gy cm2 for PTCA). The highest percentage of cine dose was in newborns (0-1 y) (CA: 92% and PTCA: 100%). As age increased, cine dose percentage decreased, whereas total radiation dose increased. Median paediatric FT and N recorded reached or even exceeded adult DRL and should be optimised. Paediatric DRL should be set.

The Amplatzer Membranous VSD Occluder and the vulnerability of the atrioventricular conduction system.

Transcatheter closure of ventricular septal defects with the Amplatzer Membranous VSD Occluder has yielded promising initial results, but disturbances of conduction, including complete heart block, have been reported. We report our experience with the Amplatzer occluder in 35 patients with a median age 4.5 years, the defects being sized angiographically at 4.4 plus or minus 1.1 millimetres, with a range from 3 to 8 millimetres, and the size of the occluder varying from 4 to 12 millimetres. Over a median follow-up of 2.5 years, the rate of complete closure was 87% and 91%, at 1 and 2 years respectively, while 2 patients required surgical closure of the defect subsequent to the insertion of the device. Persistent regurgitation across the tricuspid valve related to the occluder was observed in 3 patients, and in 6 patients across the aortic valve. Abnormalities of conduction related to the procedure were noted in 7 patients, one-fifth of the cohort. The disturbances were transient in 1 patient, but permanent in 6, in one of the latter progressing after 6 months from left bundle branch block to intermittent Mobitz II second-degree atrioventricular block in association with expansion of the occluder. We conclude that transcatheter closure of perimembranous ventricular septal defects with the Amplatzer occluder is effective with limited complications, but the incidence of immediate and progressive disturbances of conduction related to the proximity of conduction tissues to the rims of the occluder stress the importance of larger and longer studies to assess the safety of this procedure.

Transcatheter closure of coronary arterial fistulas using the new Amplatzer vascular plug.

We report our initial experience in using the Amplatzer vascular plug for closure of coronary arterial fistulas. The self-expanding, cylindrical, device is made from Nitinol wire mesh, and is available from 4 to 16 millimetres in diameter. We have now used the device to close fistulas in 3 patients, aged from 3 to 14 years, who presented with ratios of pulmonary-to-systemic flow from 1.5 to 3. In 2 patients, fistulas arising from the proximal right and left coronary arteries, with maximal diameters of 9 and 10 millimetres, respectively, had their narrowest diameter, of 6 millimetres, proximal to the entrance into the right atrium via a saccular aneurysm. The third fistula, with a maximal diameter of 16 millimetres, and with its origin from the circumflex coronary artery, entered the right atrium with nearly unrestricted flow, its narrowest diameter being 8 millimetres. For interventional closure, we chose plugs twice the diameter of the narrowest segment of the fistula, thus using 2 devices of 12 millimetres and one of 16 millimetres diameter. An arteriovenous loop was established through the fistula by snaring an exchange guide wire. Using a 7 or 8 French guide catheter inserted through the femoral vein, all plugs were placed at the narrowest segment of the fistula, leading to immediate complete closure of 2 fistulas. The third patient, with a fistula of the circumflex coronary artery, who received the largest plug initially had residual flow, but the fistula was found to be completely occluded at 12 months follow-up examination. We have demonstrated, therefore, safe and effective usage of the new vascular plug for transcatheter closure of moderate- to large-sized coronary arterial fistulas. The plug offers an alternative to cardiac surgery, or occlusion using coils.

Doppler tissue imaging evaluation of right ventricular function at rest and during dobutamine infusion in patients after repair of tetralogy of Fallot.

BACKGROUND: Reliable, non-invasive evaluation of right ventricular function, especially in congenital heart disease, is challenging. OBJECTIVES: The aim of this study was to evaluate Doppler tissue imaging (DTI) parameters of lateral tricuspid annular motion, mean rate of pressure rise during RV contraction (mean dP/dt) and indexed right ventricular (RV) stroke volume (RVSVi) as RV function indices in repaired tetralogy of Fallot (TOF). METHODS: DTI evaluation was performed in 25 repaired-TOF patients, aged 11+/-6, at rest and during dobutamine infusion and 20 controls at rest. RESULTS: TOF patients had lower (P<0.05) peak systolic velocity (Sa) (11.4+/-4 vs. 13.7+/-3.1 cm/s), early diastolic velocity (Ea) (11+/-3.1 vs. 16.3+/-3.5 cm/s) and Sa/time from onset of QRS to Sa (Sa/Q-Sa) (68.8+/-26.4 vs. 92.3+/-29.4 cm/s2) versus controls. Dobutamine increased (P<0.01) Sa (11.4+/-2.8-17.7+/-4.7 cm/s), Ea (11+/-3.1-15.6+/-3.9 cm/s), late diastolic velocity (Aa) (8.4+/-2-14.8+/-5 cm/s), Sa/Q-Sa (68.8+/-26.4-17 6.8+/-84.5 cm/s2), mean dP/dt (180+/-74-537+/-37 2 mmHg/s), and RVSVi (7.8+/-3.9-11.9+/-5.6 L/min/m2). RVSVi increase correlated (P<0.01) with that in Sa (r=0.6), Ea (r=0.5), Sa/Q-Sa (r=0.71), and mean dP/dt (r=0.57) while mean dP/dt increase correlated strongly with Sa/Q-Sa increase (r=0.88). CONCLUSION: DTI evaluation of tricuspid annular motion during dobutamine infusion in repaired TOF correlates with dP/dt and RV stroke volume and may help in assessing RV function and reserve.

Bosentan induces clinical, exercise and hemodynamic improvement in a pre-transplant patient with plastic bronchitis after Fontan operation.

We present a 14-year-old pre-transplant boy with elevated pulmonary pressure and plastic bronchitis after Fontan operation despite stent fenestration, who improved with long-term oral administration of the endothelin antagonist, bosentan. Bosentan improved the patient's symptoms and aortic saturation, World Health Organization class, maximal and sub-maximal exercise capacity, Borg dyspnea index, invasively measured mean pulmonary pressure, pulmonary blood flow and pulmonary vascular resistance. This is the first literature report examining the effect of endothelin antagonism in failing Fontan circulation and showing clinical, exercise and hemodynamic improvement with bosentan in a pre-transplant Fontan patient with high pulmonary pressure and plastic bronchitis.

Normative angiographic data relating to the dimensions of the aorta and pulmonary trunk in children and adolescents.

BACKGROUND: Definition of normative data of the great arteries from neonatal to adult ages may aid in assessment of the growth of cardiovascular structures, thus guiding the timing and type of intervention in patients with congenital cardiac disease. METHODS: We calculated the cross-sectional areas of the arterial roots at the basal attachment of the valvar leaflets, the sinuses, and standardized distal sites using cineangiograms of 59 normal children and adolescents with mean age of 5.4 plus or minus 4.7 years and a range from 0.1 to 16 years, the children having a mean weight of 21.2 plus or minus 15.7 kilograms, with a range from 2.2 to 68 kilograms, and mean height of 108 plus or minus 35 centimetres, with a range from 43 to 184 centimetres. Values at each site were calculated averaging end-diastolic and end-systolic measurements, and indexed to body surface area. Results are expressed as the mean plus or minus the standard deviation. RESULTS: The diameter of the aortic root at the basal attachment of the leaflets was 249 plus or minus 26, the midpoint of the sinuses 379 plus or minus 59, the sinutubular junction 290 plus or minus 58, the isthmus 158 plus or minus 36, the postisthmic region 152 plus or minus 33, and the descending aorta at the level of diaphragm 130 plus or minus 18 millimetres squared per metre squared. The pulmonary root measured at the basal attachment of the leaflets was 253 plus or minus 28, the midpoint of the sinuses 352 plus or minus 58, the sinutubular junction 293 plus or minus 58, the right pulmonary artery 176 plus or minus 25, the left pulmonary artery 153 plus or minus 20, and sum of right and left pulmonary arteries 330 plus or minus 37 millimetres squared per metre squared. All indexes were consistent over a wide range for body surface areas. CONCLUSIONS: Definition of normative data of the great vessels may aid in the evaluation of congenital or acquired abnormalities, serving as guidelines for intervention during medical or surgical management and follow-up.

Transcatheter embolization of recanalized coronary artery fistula with Nit-Occlud device.

Congenital coronary artery fistula is a rare anomaly with varying symptomatology that may be addressed with surgical or interventional closure. Recanalization after complete occlusion of a coronary artery fistula has only been reported after surgical but not after interventional closure. We present a case of coronary artery fistula recanalization after angiographically documented complete transcatheter occlusion with Gianturco coils. The fistula was successfully managed by transcatheter implantation of a Nit-Occlud system, originally designed for interventional closure of patent ductus arteriosus.

Diverse experience with the CardioSEAL and STARFlex septal occluders.

Apart from closure of atrial septal defects, there is little information concerning the use of the CardioSEAL family of occluders in congenitally malformed hearts. We review here our initial experience using the CardioSEAL and STARFlex occluders in 12 patients aged 17.3 +/- 11.2 years, with a range from 4 to 34 years. Of the patients, 5 had fenestrated extracardiac Fontan procedures, 5 had persistent patency of the arterial duct, 1 had a leak across a Mustard baffle, and the final patient had a huge pulmonary arteriovenous malformation. We implanted successfully 9 CardioSEAL, and 3 STARFlex occluders, with sizes from 17 to 40 mm. In one patient, the occluder embolized to the right pulmonary artery, from where it was retrieved through the catheter. In two patients, there was a trivial residual leak immediately after implantation, but no patient had a residual leak after 6 months of follow-up. We noted improved ventricular dimensions, without any fractures of the arms of the occluders, perforations, or disturbances of flow after 2.4 +/- 0.9 years of follow-up. We have demonstrated, therefore, the versatility of the CardioSEAL and STARFlex occluders, which have been used safely and effectively to close a variety of intra and extracardiac communications other than atrial septal defects.

Pancreatitis-associated splenic artery pseudoaneurysm: endovascular treatment with self-expandable stent-grafts.

We present a patient with a splenic artery pseudoaneurysm (SAPA) treated with placement of self-expandable stent-grafts. The procedure was complicated by stent-graft migration, but successful management resulted in lasting exclusion of the SAPA, while the patency of the splenic artery was preserved. This is the first report of self-expandable stent-graft treatment of SAPA.

"Absent" pulmonary artery in one adult and five pediatric patients: imaging, embryology, and therapeutic implications.

OBJECTIVE: The purpose of this article is to present serial clinical and imaging findings for the "absent" pulmonary artery. Data from six patients with this condition (five unilateral cases and one bilateral case) provide evidence concerning its embryology and illustrate the therapeutic implications of surgical intervention. CONCLUSION: In our series, we found the anatomy of the absent pulmonary artery to be consistent with a distal ductal origin and involution of the proximal sixth aortic arch. The absent pulmonary artery is a distinct embryologic entity that requires early detection and detailed investigation. Early surgical intervention may be justified in selected patients.