Cardiac ion channel gene mutations in Greek long QT syndrome patients.

The long QT syndrome (LQTS) is an inherited cardiac arrhythmia that may lead to sudden death in the absence of structural heart disease. Mutations in the cardiac potassium and sodium channel genes can be found in approximately 70 percent of patients with a highly probable clinical diagnosis. In this study, we aimed to genotype and explore the yield of genetic testing of LQTS patients from Greece, for whom there are no collective published data available. We clinically evaluated and genetically screened 17 unrelated patients for mutations in the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 cardiac ion channel genes. Genetic testing was positive in 6 out of 8 patients with a highly probable clinical diagnosis of LQTS and negative for all the other patients. Two patients carried KCNQ1 mutations (c.580G>C, c.1022C>T), while 4 patients carried KCNH2 mutations (c.202T>C, c.1714G>A, c.3103delC, c.3136C>T). To the best of our knowledge, the last mentioned mutation (c.3136C>T) is novel. Moreover, 27 single-nucleotide polymorphisms (SNPs) were detected, 5 of which are novel. Our preliminary data indicate a low genetic diversity of the Greek LQTS genetic pool, and are in accordance with international data that genetic testing of the major LQTS genes is efficient in genotyping the majority of patients with a strong clinical diagnosis. Therefore, the transition of an LQTS genetic screening program from research to the diagnostic setting within our ethnic background is feasible.

Cardiac resynchronisation therapy in paediatric and congenital heart disease: differential effects in various anatomical and functional substrates.

BACKGROUND: Cardiac resynchronisation therapy (CRT) is increasingly used in children in a variety of anatomical and pathophysiological conditions, but published data are scarce. OBJECTIVE: To record current practice and results of CRT in paediatric and congenital heart disease. DESIGN: Retrospective multicentre European survey. SETTING: Paediatric cardiology and cardiac surgery centres. PATIENTS: One hundred and nine patients aged 0.24-73.8 (median 16.9) years with structural congenital heart disease (n = 87), congenital atrioventricular block (n = 12) and dilated cardiomyopathy (n = 10) with systemic left (n = 69), right (n = 36) or single (n = 4) ventricular dysfunction and ventricular dyssynchrony during sinus rhythm (n = 25) or associated with pacing (n = 84). INTERVENTIONS: CRT for a median period of 7.5 months (concurrent cardiac surgery in 16/109). MAIN OUTCOME MEASURES: Functional improvement and echocardiographic change in systemic ventricular function. RESULTS: The z score of the systemic ventricular end-diastolic dimension decreased by median 1.1 (p<0.001). Ejection fraction (EF) or fractional area of change increased by a mean (SD) of 11.5 (14.3)% (p<0.001) and New York Heart Association (NYHA) class improved by median 1.0 grade (p<0.001). Non-response to CRT (18.5%) was multivariably predicted by the presence of primary dilated cardiomyopathy (p = 0.002) and poor NYHA class (p = 0.003). Presence of a systemic left ventricle was the strongest multivariable predictor of improvement in EF/fractional area of change (p<0.001). Results were independent of the number of patients treated in each contributing centre. CONCLUSION: Heart failure associated with ventricular pacing is the largest indication for CRT in paediatric and congenital heart disease. CRT efficacy varies widely with the underlying anatomical and pathophysiological substrate.

Accelerated ventricular rhythm in the neonatal period: a review and two new cases in asymptomatic infants with an apparently normal heart.

UNLABELLED: Accelerated ventricular rhythm (AVR) was observed in two newborn infants. In the first case, arrhythmia was noted during the foetal period. Both neonates were asymptomatic and had no evidence of cardiac disease. The arrhythmia eventually disappeared when the infants were 4 mo and 24 d old, respectively. AVR in the neonatal period is reviewed in this report and recent information regarding appropriate diagnostic evaluation, differentiation from ventricular tachycardia and treatment is outlined. CONCLUSION: Accelerated ventricular rhythm is a benign and self-limited arrhythmia in the neonatal period. However, it is important to differentiate it from other serious rhythm disorders, mainly ventricular tachycardia, in order to avoid unnecessary and potentially harmful treatment and to relieve parental anxiety.

Early results after transatrial/transpulmonary repair of tetralogy of Fallot.

OBJECTIVES: Right ventricular (RV) dysfunction is a significant cause of morbidity and mortality after surgical correction of tetralogy of Fallot (TOF). Transatrial/transpulmonary repair avoids a ventriculotomy (in contrast to the transventricular approach) emphasizing maximal preservation of RV structure and function. We have adopted this technique as less traumatic for the right ventricle. This study evaluates the early surgical results of our approach. METHODS: Between September 1997 and July 2001, 110 consecutive patients with TOF were referred to our unit for surgical therapy. Of these, 14 were unsuitable for repair and underwent aortopulmonary shunting+/-pulmonary artery patching. In the remaining 96 patients (median age 1.4 years), complete transatrial/transpulmonary repair was performed. Previously placed shunts (ten patients) were taken down and any secondary stenoses or branch pulmonary artery distortion repaired. In all cases, subpulmonary resection and ventricular septal defect (VSD) closure were accomplished transatrially. Whenever pulmonary valvotomy and valve ring widening were necessary, it was achieved through a pulmonary arteriotomy. In 84 patients the main pulmonary artery was augmented with an autologous pericardial patch, and in 23 the patch was extended to pulmonary artery branch(es). A limited (<1cm ) or extended (>1cm, but

Diagnosis and management of pulmonary arteriovenous malformations.

Pulmonary arteriovenous malformation is a rare anomaly that presents in several different ways. It can present as an isolated finding, or more often in the context of hereditary haemorrhagic telangiectasia. It can also complicate palliative surgery such as the Glenn operation for complex congenital heart disease with single ventricle physiology. Its management includes transcatheter embolization, which is the preferred mode of therapy, surgery (including resection of the affected lobe, segment, or the fistula itself), or rarely, medical therapy. Complications of the disease itself and of various modes of treatment are relatively common, and patients require close surveillance for possible recurrence, or development of new fistulas. In cases related to the Glenn operation, redirection of hepatic venous flow or heart transplantation may cure the problem.

Transcatheter occlusion of a large pulmonary arteriovenous malformation with use of a Cardioseal device.

Large pulmonary arteriovenous malformations (PAVMs) carry a significant risk of neurologic complications and present technical difficulties in transcatheter treatment with use of coils or detachable balloons. A 26-year-old man with a giant PAVM, who had undergone unsuccessful attempted closure with use of a Gianturco-Grifka occlusion device in the past, underwent successful transcatheter embolization with two Cardioseal double umbrella devices designed for occlusion of intracardiac communications. The procedure was technically easy, had no complications, and provided sustained improvement in arterial saturation and exercise tolerance during follow-up. Transcatheter double umbrella device occlusion of large arteriovenous malformations is feasible and should be considered, especially for very large fistulas.

Congenital left ventricular aneurysm: clinical, imaging, pathologic, and surgical findings in seven new cases.

BACKGROUND: Congenital left ventricular aneurysm is a poorly understood and potentially lethal entity. Methods and Results In a clinicopathologic study of 7 new cases, the major presenting features in 6 patients were congestive heart failure in 4, ventricular arrhythmias in a 32-week fetus, and multiple congenital anomalies in a fetus with trisomy 13. Accurate diagnosis was achieved in all 3 living patients by echocardiography, angiocardiography, and magnetic resonance imaging. The aneurysm was predominantly apical in 3 and involved most of the left ventricular free wall in 4. Of the 3 living patients, medical management alone sufficed in 2. The third, a newborn boy, underwent a new and successful aneurysm-exclusion left ventriculoplasty. The mitral valve was abnormal in all 4 autopsied cases, the papillary muscles being short, thin, or absent. The aneurysm was thinner and its area was larger than that of the nonaneurysmal left ventricle in all necropsied patients. CONCLUSIONS: Congenital left ventricular aneurysm appears to be a developmental anomaly, an idiopathic dysplasia of left ventricular endocardium and myocardium. No evidence of a viral etiology was found. Some neonates can be managed medically, but others require urgent surgical intervention. A new surgical operation is presented, a functional left ventricular aneurysmectomy that minimizes intraoperative and postoperative blood loss and that preserves the coronary arteries.

Transcatheter occlusion of atrial baffle leak after mustard repair.

We present a case of transcatheter closure of an atrial baffle leak with significant systemic to pulmonary atrium shunt in a patient late after Mustard operation and pulmonary valvotomy for transposition of the great arteries. This procedure alleviated the need for reoperation in a high-risk symptomatic patient. Cathet. Cardiovasc. Intervent. 51:305-307, 2000.

Radiofrequency catheter ablation of supraventricular tachycardia substrates after mustard and senning operations for d-transposition of the great arteries.

OBJECTIVES: The purpose of this study was to determine the efficacy and risks of radiofrequency ablation of various forms of supraventricular tachycardia after Mustard and Senning operations for d-transposition of the great arteries. BACKGROUND: In this patient group, the reported success rate of catheter ablation of intraatrial reentry tachycardia is about 70% with a negligible complication rate. There are no reports of the use of radiofrequency ablation to treat other types of supraventricular tachycardia. METHODS: Standard diagnostic criteria were used to determine supraventricular tachycardia type. Appropriate sites for attempted ablation included 1) intraatrial reentry tachycardia: presence of concealed entrainment with a postpacing interval similar to tachycardia cycle length; 2) focal atrial tachycardia: a P-A interval < or =-20 ms; and 3) typical variety of atrioventricular (AV) node reentry tachycardia: combined electrographic and radiographic features. RESULTS: Nine Mustard and two Senning patients underwent 13 studies to successfully ablate all supraventricular tachycardia substrates in eight (73%) patients. Eight of eleven (73%) patients having intraatrial reentry tachycardia, 3/3 having typical AV node reentry tachycardia, and 2/2 having focal atrial reentry tachycardia were successfully ablated. Among five patients having intraatrial reentry tachycardia (IART) and not having ventriculoatrial (V-A) conduction, two suffered high-grade AV block when ablation of the systemic venous portion of the medial tricuspid valve/inferior vena cava isthmus was attempted. CONCLUSIONS: Radiofrequency catheter ablation can be effectively and safely performed for certain supraventricular tachycardia types in addition to intraatrial reentry. A novel catheter course is required for slow pathway modification. High-grade AV block is a potential risk of lesions placed in the systemic venous medial isthmus.

Radiofrequency catheter ablation of multiple haemodynamically unstable ventricular tachycardias in a patient with surgically repaired tetralogy of Fallot.

A patient with repaired tetralogy of Fallot presented with recurrent syncope and had multiple haemodynamically unstable ventricular tachycardias unresponsive to antiarrhythmic medications. Ventricular tachycardias became haemodynamically tolerated with amiodarone, procainamide and dopamine, permitting activation and entrainment mapping. Radiofrequency ablation of three tachycardia circuits was performed. Ventricular tachycardia could not be induced 1 week, and 3 and 9 months later. Radiofrequency ablation is feasible for multiple, haemodynamically unstable ventricular tachycardias in repaired tetralogy of Fallot.

Double-inlet and double-outlet left ventricle in situs inversus.

Double-outlet left ventricle is a rare congenital cardiac malformation that has been traditionally difficult to diagnose accurately. We report a unique case of situs inversus totalis, L-loop, double-inlet left ventricle and double-outlet left ventricle with pulmonary stenosis, diagnosed mainly by transesophageal echocardiography and magnetic resonance imaging.

Pathologic anatomy of corrected transposition of the great arteries: medical and surgical implications.

BACKGROUND: Because the double-switch operation (atrial switch plus arterial switch) has recently become feasible in selected patients with congenitally physiologically corrected transposition of the great arteries, a detailed understanding of the pathologic anatomy is now mandatory for cardiologists, radiologists, and surgeons. METHODS: A detailed study of the pathologic anatomy, the clinical implications, and the surgical implications was undertaken on 33 postmortem cases with two ventricles. A companion study was also performed of 44 postmortem cases with functionally only one ventricle. Hence this was an investigation of 77 postmortem cases. RESULTS: Three main anatomic types of corrected transposition of the great arteries (TGA) with two ventricles were found: (1) TGA with solitus atria (S), L-loop ventricles (L), and L-TGA (L), that is, TGA [S,L,L] in 31 cases (94%); (2) TGA with solitus atria (S), L-loop ventricles (L), and D-TGA (D), that is, TGA [S,L,D] in 1 case (3%); and (3) TGA with inverted atria (I), D-loop ventricles (D), and D-TGA (D), that is, TGA [I,D,D] in 1 case (3%). Associated malformations resulted in 13 anatomic subtypes. In classical corrected TGA [S,L,L] with two ventricles, anomalies of the left-sided systemic tricuspid valve were present in 97%, with malformations of the left-sided systemic right ventricle in 91%. CONCLUSIONS: The findings in corrected TGA with two ventricles and in cases with single ventricle support the view that anatomic repair such as the double-switch procedure, or left-sided right ventricle bypass such as the modified Norwood procedure followed by the modified Fontan procedure, is indicated in selected patients.

Late enlargement of radiofrequency lesions in infant lambs. Implications for ablation procedures in small children.

BACKGROUND: Despite the current clinical use of radiofrequency (RF) catheter ablation in infants, the acute and late effects of RF lesion production in immature myocardium remain unknown. This study was specifically designed to investigate the pathology of RF lesions in developing sheep myocardium. METHODS AND RESULTS: In study 1, RF lesions were made on the epicardial left ventricular surface of the beating heart in 15 sheep, 5 approximately 4 weeks of age (11.0 +/- 1.0 kg) and 10 approximately 8 weeks of age (23.8 +/- 3.4 kg), to assess the effects of RF application duration (10 to 90 seconds) and electrode tip temperature (45 degrees to 90 degrees C) on lesion size in immature myocardium. Lesion width and depth increased asymptotically with RF duration, to 7.0 +/- 0.7 and 4.8 +/- 1.0 mm at 90 seconds, respectively. The time to reach one-half lesion size was 6.5 seconds for width and 12.0 seconds for depth. Lesion width increased nearly linearly with tip temperature above 50 degrees C, but depth followed a sigmoid relation, with no increase above 80 degrees C. In study 2, RF lesions were made in all four cardiac chambers under fluoroscopic guidance in 19 infant sheep (10.9 +/- 1.4 kg). Lesion sizes and histological characteristics were assessed acutely (acute, n = 5), at 1.07 +/- 0.02 months (1 month, n = 5), and at 8.5 +/- 0.5 months (late, n = 9). Atrial and ventricular lesions but not atrioventricular groove lesions apparently increased in size during the follow-up period. Atrial lesions width increased from 5.3 +/- 0.5 to 8.7 +/- 0.7 mm at 1 month (164%) but did not increase further at late follow-up, while ventricular lesion width increased from 5.9 +/- 0.8 to 10.1 +/- 0.7 mm (171%) at late follow-up but was not significantly changed at 1 month. Histological evaluation revealed replacement of normal myocytes with fibrous and elastic tissue at 1 month and late follow-up in all locations but also demonstrated a poorly delineated border with multiple extensions of fibrous and elastic tissue into surrounding normal myocardium in late ventricular lesions. CONCLUSIONS: RF lesion formation in immature sheep myocardium is similar to that in adult myocardium acutely but is associated with late lesion enlargement and fibrous tissue invasion of normal myocardium. These findings may have implications for clinical RF ablation procedures in infants.

Polysplenia with pulmonary arteriovenous malformations.

A patient with polysplenia syndrome, dextrocardia, left atrial isomerism, normal great vessel relationships, and no intracardiac shunts developed progressive cyanosis and clubbing. Pulmonary arteriovenous malformations (PAVMs) were diagnosed by angiography and confirmed by lung biopsy. Superior mesenteric arteriogram revealed hypoplasia of the intrahepatic portal vein branches and a portosystemic shunt. The possible etiologies of PAVMs are discussed.

Use of balloon occlusion to improve visualization of anomalous pulmonary venous return in an adult with cor triatriatum.

Cor triatriatum, although rare in adults, is often associated with anomalous pulmonary venous return. Accurate diagnosis of the pulmonary venous return and its anatomic connections is essential in planning proper surgical correction. This case illustrates the advantage of selective pulmonary artery angiography in obtaining accurate detail of the pulmonary venous anatomy from digital subtraction levophase images. Selective right and left pulmonary angiography was performed using a balloon catheter to simultaneously occlude the opposite pulmonary artery. This technique was well tolerated and greatly enhanced visualization of the anomalous pulmonary venous connections, allowing proper planning for corrective surgery.