Transcatheter mitral valve-in-valve implantation in a pediatric patient.

An 11-year-old girl, with 25 mm mosaic tissue valve presented with clinical and echocardiographic appearance of stenotic mitral valve prosthesis. Her condition was treated via a transcatheter valve-in-valve implantation using a 23 mm Edwards Sapien 3, with satisfactory outcome.

Transcatheter Tricuspid Valve-in-Valve Implantation for the Treatment of Dysfunctional Surgical Bioprosthetic Valves: An International, Multicenter Registry Study.

BACKGROUND: Off-label use of transcatheter aortic and pulmonary valve prostheses for tricuspid valve-in-valve implantation (TVIV) within dysfunctional surgical tricuspid valve (TV) bioprostheses has been described in small reports. METHODS AND RESULTS: An international, multicenter registry was developed to collect data on TVIV cases. Patient-related factors, procedural details and outcomes, and follow-up data were analyzed. Valve-in-ring or heterotopic TV implantation procedures were not included. Data were collected on 156 patients with bioprosthetic TV dysfunction who underwent catheterization with planned TVIV. The median age was 40 years, and 71% of patients were in New York Heart Association class III or IV. Among 152 patients in whom TVIV was attempted with a Melody (n=94) or Sapien (n=58) valve, implantation was successful in 150, with few serious complications. After TVIV, both the TV inflow gradient and tricuspid regurgitation grade improved significantly. During follow-up (median, 13.3 months), 22 patients died, 5 within 30 days; all 22 patients were in New York Heart Association class III or IV, and 9 were hospitalized before TVIV. There were 10 TV reinterventions, and 3 other patients had significant recurrent TV dysfunction. At follow-up, 77% of patients were in New York Heart Association class I or II (P<0.001 versus before TVIV). Outcomes did not differ according to surgical valve size or TVIV valve type. CONCLUSIONS: TVIV with commercially available transcatheter prostheses is technically and clinically successful in patients of various ages across a wide range of valve size. Although preimplantation clinical status was associated with outcome, many patients in New York Heart Association class III or IV at baseline improved. TVIV should be considered a viable option for treatment of failing TV bioprostheses.

A Zebrafish Loss-of-Function Model for Human CFAP53 Mutations Reveals Its Specific Role in Laterality Organ Function.

Establishing correct left-right asymmetry during embryonic development is crucial for proper asymmetric positioning of the organs. Congenital heart defects, such as dextrocardia, transposition of the arteries, and inflow or outflow tract malformations, comprise some of the most common birth defects and may be attributed to incorrect establishment of body laterality. Here, we identify new patients with dextrocardia who have mutations in CFAP53, a coiled-coil domain containing protein. To elucidate the mechanism by which CFAP53 regulates embryonic asymmetry, we used genome editing to generate cfap53 zebrafish mutants. Zebrafish cfap53 mutants have specific defects in organ laterality and randomization of asymmetric gene expression. We show that cfap53 is required for cilia rotation specifically in Kupffer's vesicle, the zebrafish laterality organ, providing a mechanism by which patients with CFAP53 mutations develop dextrocardia and heterotaxy, and confirming previous evidence that left-right asymmetry in humans is regulated through cilia-driven fluid flow in a laterality organ.

Acquired aortic atresia: Catheter therapy using covered stents.

INTRODUCTION: To maintain aortic continuity, aortic arch interruption is usually treated surgically. We present our experience of aortic arch reconstruction using percutaneous implantation of covered stents and mid-term follow-up. OBJECTIVE: To describe the feasibility, safety, and effectiveness using percutaneous placement of covered stents for functional aortic atresia and mid-term follow-up. METHODS: Nine patients (7 males), mean age of 30.8 ±16.2 years (range 13-58 years) and mean body weight of 65.7± 14.9 kg (range 52-95 kg), were investigated for systemic hypertension and found to have functional aortic interruption. All were treated with percutaneous perforation, combined with balloon dilation and implantation of covered stents. After stent implantation, control angiograms were performed. RESULTS: All the patients had functional aortic interruption and continuity was established by perforating the atretic segment with trans-septal Brockenbrough needle or the stiff end of a guide wire. A covered Cheatham-Platinum CP stent was used to establish the luminal continuity of the aortic arch. Angiograms after stent deployment showed good forward flow through the stent and hemodynamic assessment revealed minimal gradients across the stent. The mean invasive descending aortic systolic blood pressure before stenting was 86.6 ± 14.3 mm Hg, which increased to 116.5 ± 16.3 mm Hg, after stenting (P = 0.004). The mean invasive descending aortic diastolic blood pressure before stenting was 63.6 ± 8.1 mm Hg, which increased to 79.7 ± 13.3 mm Hg after stenting (P = 0.002). CONCLUSION: Percutaneous treatment of functional aortic atresia with covered stents is feasible, safe, and effective alternative to surgery with excellent short- and mid-term results.

Percutaneous removal of right atrial thrombus by suction technique.

We present a case of percutaneous removal of a large right atrial thrombus formed after insertion of a ventriculoatrial shunt for hydrocephalus.

Post Melody valve implant in a conduit with regurgitant native outflow tract successful closure by Amplatzer muscular device.

We describe the technique of closure of native right ventricular outflow tract by Amplatzer muscular ventricular septal defect device because of severe regurgitation in a patient who had tetralogy of Fallot repair with conduit at 3 years of age followed by percutaneous Melody valve implant 6 years later.

Williams-Beuren syndrome: computed tomography imaging review.

Williams-Beuren syndrome (WBS) affects young infants and children. The underlying etiopathogenesis of this rare disease is due to the mutation of the elastin gene that is responsible for the elasticity of the arterial wall. As a result of inadequate elastin production, the major systemic arteries become abnormally rigid and can be manifested by an impediment to the blood flow. The most common cardiovascular abnormalities encountered in WBS are supravalvular aortic stenosis, pulmonary arterial stenosis, and mitral valve prolapse. Less frequently observed cardiovascular abnormalities include coarctation of the aorta, ventricular septal defect, patent ductus, subaortic stenosis, and hypertrophic cardiomyopathy. Coronary artery stenosis and severe impediment to the bi-ventricular outflow as a result of supravalvular aortic and pulmonary artery stenosis predispose patients to sudden death. Patients with progressed arterial stenosis and severe stenosis are likely to require intervention to prevent serious complications. Rarely, imaging findings may precede clinical presentation, which allows the radiologist to participate in the patient care. However, to be more prudent, the radiologist must be accustomed to the imaging characteristics of WBS as well as the patient's clinical information, which could raise the suspicion of WBS. We performed a retrospective analysis of all the available images from patients diagnosed with WBS in last 4 years at our institution, and present key imaging findings along with a review of the literature to summarize the clinically relevant features as demonstrated by multidetector computed tomography in WBS. Cross-sectional imaging plays a vital role in the diagnosis of WBS cases with equivocal clinical features. MDCT evaluation of complex cardiovascular abnormalities of WBS including coronary artery disease is feasible with modern MDCT scanners and in the future, this approach could provide accurate information for planning, navigation, and noninvasive assessment of the secondary arterial changes in WBS and thus reducing the dependence upon invasive contrast catherization techniques.

An intronic mutation leading to incomplete skipping of exon-2 in KCNQ1 rescues hearing in Jervell and Lange-Nielsen syndrome.

Romano-Ward syndrome (RWs) and Jervell and Lange-Nielsen Syndrome (JLNs) are two inherited arrhythmia disorders caused by monoallelic or bi-allelic mutations, respectively, in the KCNQ1 or KCNE1 genes. Both disorders could cause Long QT syndrome either without deafness (RWs), or with deafness (JLNs). We have performed clinical, molecular and functional investigation in two consanguineous Arabian families with history of sudden death of several children. Importantly, none of the affected individuals had (or have) any hearing impairment. Homozygosity mapping followed by molecular analysis identified a novel splice acceptor site mutation (homozygously) in intron-1 of the KCNQ1 gene (c.387 -5T>A), in these two apparently unlinked families. RNA analysis revealed that this splice site mutation causes incomplete transcriptional aberration of the KCNQ1 gene, leaving 10% of the normal allele transcript intact, which restores the hearing function. Our molecular and functional data provide the first evidence that small amount (as low as 10%) of normal KCNQ1 current can effectively maintain the hearing function but fails to maintain cardiac repolarization characteristics within normal limits. Additionally, we have revealed four extra low frequency aberrant isoforms emphasizing the importance of intronic and other non-coding sequences in maintaining cellular homeostasis as pathologic changes in a single nucleotide can affect splicing events at distant sites. The novel KCNQ1 mutation found in this study is very likely a founder mutation in the southern province of Saudi Arabia emphasizing its screening in the LQT population in this region.

Clinical and genetic analysis of long QT syndrome in children from six families in Saudi Arabia: are they different?

Congenital long QT syndrome (LQTS) is an inherited cardiac arrhythmia disorder characterized by prolongation of the QT interval; patients are predisposed to ventricular tachyarrhythmias and fibrillation leading to recurrent syncope or sudden cardiac death. We performed clinical and genetic studies in six Saudi Arabian families with a history of sudden unexplained death of children. Clinical symptoms, ECG phenotypes, and genetic findings led to the diagnosis of LQT1 in two families (recessive) and LQT2 in four families (three recessive and one dominant). Onset of arrhythmia was more severe in the recessive carriers and occurred during early childhood in all recessive LQT1 patients. Arrhythmia originated at the intrauterine stages of life in the recessive LQT2 patients. LQT1, causing mutation c.387-5 T > A in the KCNQ1 gene, and LQT2, causing mutation c.3208 C > T in the KCNH2 gene, are presumably founder mutations in the Assir province of Saudi Arabia. Further, all LQTS causing mutations detected in this study are novel and have not been reported in other populations.

Embolized amplatzer duct occluder to aorta: Retrieval technique.

A 4-year-old girl had an Amplatzer duct occluder embolized to the descending aorta immediately after closure of patent ductus arteriosus: a novel technique of retrieval.

Chemotherapy Induced Acute Pericarditis in a Child.

A9 years boy diagnosed with nasopharyngeal carcinoma was started on chemotherapy protocol including 5-fluorouracil. After 90 hours of 5-fluorouracil infusion, he developed severe retrosternal chest pain. Electrocardiography showed signs of acute pericarditis and was managed with ibuprofen and 5-fluorouracil was discontinued. The 5-fluorouracil rarely causes cardiac complications such as angina pectoris and pericarditis in adult patients. We report acute myopericarditis in a child caused by 5-fluorouracil, which is a very rare complication of 5-fluorouracil in pediatric age group.

Congenital Long QT Syndrome: An Update and Present Perspective in Saudi Arabia.

Primary cardiac arrhythmias are often caused by defects, predominantly in the genes responsible for generation of cardiac electrical potential, i.e., cardiac rhythm generation. Due to the variability in underlying genetic defects, type, and location of the mutations and putative modifiers, clinical phenotypes could be moderate to severe, even absent in many individuals. Clinical presentation and severity could be quite variable, syncope, or sudden cardiac death could also be the first and the only manifestation in a patient who had previously no symptoms at all. Despite usual familial occurrence of such cardiac arrhythmias, disease causal genetic defects could also be de novo in significant number of patients. Long QT syndrome (LQTS) is the most eloquently investigated primary cardiac rhythm disorder. A genetic defect can be identified in ∼70% of definitive LQTS patients, followed by Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) and Brugada syndrome (BrS), where a genetic defect is found in <40% cases. In addition to these widely investigated hereditary arrhythmia syndromes, there remain many other relatively less common arrhythmia syndromes, where researchers also have unraveled the genetic etiology, e.g., short QT syndrome (SQTS), sick sinus syndrome (SSS), cardiac conduction defect (CCD), idiopathic ventricular fibrillation (IVF), early repolarization syndrome (ERS). There exist also various other ill-defined primary cardiac rhythm disorders with strong genetic and familial predisposition. In the present review we will focus on the genetic basis of LQTS and its clinical management. We will also discuss the presently available genetic insight in this context from Saudi Arabia.

Extended application of percutaneous pulmonary valve implantation.

OBJECTIVES: This study was designed to report a novel indication for percutaneous pulmonary valve implantation in patients with previous right ventricular outflow tract (RVOT) patch. BACKGROUND: Current indications for percutaneous pulmonary valve implantation are limited to patients who had pulmonary valve stenosis and/or regurgitation in a right ventricle-to-pulmonary artery conduit. Percutaneous pulmonary valve implantation has not been previously reported in patients with severe pulmonary valve regurgitation following repair of tetralogy of Fallot (TOF) using RVOT patch. METHODS: After assessment of the RVOT patch in multiple projections, a catheter was placed in a distal pulmonary artery branch. In patients with an RVOT patch, sizing of the narrowest diameter of the RVOT patch by manual inflation of a sizing balloon was performed; a stent was placed into the RVOT patch at the level of the narrowest area to anchor the stent and to create an artificial conduit to place the Melody valve. The percutaneous valve was then implanted. RESULTS: Seven females and 6 males with a mean age of 14.3 years and mean body weight 45 kg had successful percutaneous implantation of the Melody valve. Four patients had previous repair of TOF using RVOT patch. All patients were discharged within 2 days after the procedure without complications. After a mean of 4 months follow-up all patients were alive and well. Transthoracic echocardiography showed competent pulmonary valve. Chest X-ray showed no stent migration or fracture. CONCLUSIONS: Percutaneous pulmonary valve implantation can be performed in patients with pulmonary valve regurgitation, including those with previous RVOT patch using pre-stenting techniques, with satisfactory results.

Effects of transcatheter closure of Fontan fenestration on exercise tolerance. kidecho@yahoo.com.

Baffle fenestration is associated with a significantly better outcome in standard and high-risk patients undergoing completion of Fontan. We report the effects of subsequent transcatheter closure of fenestration on exercise capacity and oxygen saturation. Sixteen patients with a mean age of 10.3 years underwent Amplatzer septal occluder (ASO) device transcatheter closure of Fontan fenestration. All had a fenestrated Fontan operation 6 month to 8 years prior to the procedure. A stress test was performed before and after device closure of fenestration in 14 patients (2 patients did not tolerate stress test before the procedure). The fenestrations in all patients were successfully occluded with the use of the Amplatzer device occluder. No complications occurred during or after the procedure. O2 saturation increased from a mean 85.1 +/- 7.89% to 94.5 +/- 3.63% (p < 0.01) at rest and from 66.2 +/- 12.86% to 87.2 +/- 8.64% (p < 0.01) following exercise. Exercise duration has also increased from 8.22 +/- 2.74 min to 10.29 +/- 1.91 min (p < 0.05). Transcatheter closure of Fontan fenestration increases the duration of exercise capacity and increases O2 saturation at rest and after exercise.

Severity scoring system for ventricular septal defect.

INTRODUCTION: Residual ventricular septal defect (RVSD) occurs in one-third of patients undergoing patch closure of congenital VSD. Indications for re-intervention are often based on either patient's symptoms or echocardiographic or hemodynamic studies. We report a novel scoring system for RVSD that takes into account all of the above criteria. METHODS: RVSD size, Qp:Qs ratio, RV to LV pressure ratio, and heart failure symptoms are scored as follows: (A) RVSD size is subdivided into three categories: <3 mm, 3 to <4 mm, and >/=4 mm; (B) Qp:Qs ratio is also subdivided into three categories: <1.5, 1.5 to <2, and >/=2.0; (C) The right and left ventricular pressure ratio is subdivided into the following: <0.5, 0.5 to <0.75, and >/=0.75; (D) Heart failure symptoms are subdivided into three categories: NYHA class II/III, NYHA class IV, and pulmonary edema requiring assisted ventilation. Each of these categories is given a score value of one (less severe), two (intermediate severity), and three (severe). Intra-operative severity score of RVSD is calculated by adding the total score of A, B, and C. For post-operative RVSD severity, the score values of A, B, C, and D are added. According to the total score, the clinical significance of an intra-operative RVSD is then defined as mild, moderate, or severe for a score of /=6, respectively. Similarly, post-operative RVSD is then labeled as mild, moderate, or severe for a score of /=8, respectively. CONCLUSION: From our experience and review of literature, severe RVSD (and moderate VSD post Tetrology of Fallot (TOF) repair) require immediate closure of RVSD. Other patients with mild or moderate RVSD need close follow-up with a repeat of transesophageal echocardiography (TEE) before discharge, and six months after surgery. This scoring system, however, needs further prospective evaluation to assess its potential role in decision-making in the management of RVSD.

Recurrent intrauterine fetal loss due to near absence of HERG: clinical and functional characterization of a homozygous nonsense HERG Q1070X mutation.

BACKGROUND: Inherited arrhythmias may underlie intrauterine and neonatal arrhythmias. Resolving the molecular genetic nature of these rare cases provides significant insight into the role of the affected proteins in arrhythmogenesis and (extra-) cardiac development. OBJECTIVE: The purpose of this study was to perform clinical, molecular, and functional studies of a consanguineous Arabian family with repeated early miscarriages and two intrauterine fetal losses in the early part of the third trimester of pregnancy due to persistent arrhythmias. METHODS: In-depth clinical investigation was performed in two siblings, both of whom developed severe arrhythmia during the second trimester of pregnancy. Homozygosity mapping with microsatellite repeat polymorphic markers encompassing various cardiac ion channel genes linked to electrical instability of the heart was performed. Screening of the candidate gene in the homozygous locus was performed. Biochemical and electrophysiologic analysis was performed to elucidate the function of the mutated gene. RESULTS: Screening of the HERG gene in the homozygous locus detected a homozygous nonsense mutation Q1070X in the HERG C-terminus in affected children. Biochemical and functional analysis of the Q1070X mutant showed that although the mutant HERG had the ability to traffic to the plasma membrane and to form functional channels, it was destroyed by the nonsense-mediated decay (NMD) pathway before its translation. NMD leads to near absence of HERG in homozygous Q1070X mutation carriers, causing debilitating arrhythmias (prior to birth) in homozygous carriers but no apparent phenotype in heterozygous carriers. CONCLUSION: Homozygous HERG Q1070X is equivalent to near functional knockout of HERG. Clinical consequences appear early, originating during the early stages of embryonic life. The NMD pathway renders HERG Q1070X functionless before it can form a functional ion channel.