Prinzmetal angina in a child with actin gene ACTC1 mutation.

Prinzmetal angina is a rare cause of intermittent chest pain in paediatrics. Here, we report the case of a 2-year-old female who presented with episodic chest pain, malaise, diaphoresis, fatigue, and poor perfusion on exam. During her hospitalisation, these episodes were associated with significant low cardiac output as evidenced by lactic acidosis and low mixed venous oxygen saturations. Her workup revealed an actin alpha cardiac muscle 1 (ACTC1) gene mutation and associated left ventricular non-compaction with decreased systolic function. She was started on oral heart failure medications as well as a calcium channel blocker but continued to have episodes which were found to promptly resolve with nitroglycerine. She was ultimately listed for cardiac transplant given her perceived risk of sudden death.

Ablation of intra-atrial reentrant tachycardias in adults with congenital heart disease: islands, isthmuses, channels, and walls.

PURPOSE OF REVIEW: The adult congenital heart patient population is rapidly growing due to increasing survival rates, and they often face chronic physiologic challenges as sequalae of both their defects and repairs. Among the most common sequalae are arrhythmias. Here we describe intra-atrial reentrant tachycardia (IART), one of the most commonly seen arrhythmias in the adult congenital heart population, and the approaches to successful ablation in adult congenital heart patients. RECENT FINDINGS: IART has increasing ablation success rates due to the increasing exposure of electrophysiologists to congenital cases, advances in technology, and the increasing application of both our pediatric congenital knowledge and adult acquired knowledge to the adult congenital population. SUMMARY: IART is a frequently seen arrhythmia in the adult congenital population, and it can have life-threatening consequences in the setting of congenital disease. Ablation techniques and treatment rates have improved over time, despite the challenges these cases present to clinicians; success of the ablation depends on careful, often creative, preplanning, and understanding of the complex individualized anatomy and circuits of the patient.

Percutaneous thrombectomy of AVF: immediate success and long-term patency rates.

The purpose of this study was to report the results obtained in a cohort of 520 cases of thrombosed arteriovenous fistulas (AVF) treated by percutaneous intervention over a period of 8 years. The methods used varied according to the individual characteristics of the case. A clinical success rate of 91.1% was obtained with no significant difference being noted among radial-cephalic, brachial-cephalic, and brachial-basilic AVFs. The mean primary patency for this group was 227.3 ± 14.6 days, and the mean assisted primary patency was 677.2 ± 44.6 days. The lower arm AVFs had both a primary patency and an assisted primary patency that were significantly better than the upper arm cases (p = 0.006 and 0.002, respectively). The primary patency for radial-cephalic AVFs was significantly better than that for brachial-cephalic AVFs (p = 0.021), but not for brachial-basilic cases (p = 0.122). Assisted primary patency for radial-cephalic cases was significantly superior to the values for either patients with a brachial cephalic (p = 0.046) or a brachial-basilic (p = 0.004). Complications occurred in seven cases (1.3%), all of which were venous ruptures. Blood flow was affected in four cases. Only one of these was salvaged with angioplasty balloon tamponade. In the remaining three cases, the AVF was lost.

Outcomes of arteriovenous grafts following simultaneous thrombectomy and stent graft placement across the venous anastomosis.

Arteriovenous grafts (AVGs) suffer from high thrombosis rates. It is not known whether placement of stent grafts at the venous anastomosis (VA) of thrombosed AVGs would impact future thrombosis. This is a retrospective study evaluating a group of AVGs that underwent endovascular thrombectomy with placement of a stent graft at their VA. The study period was a minimum of 1 year or until kidney transplantation or death. Primary and secondary AVG patency rates were obtained using Kaplan-Meier survival estimates. Demographic parameters were analyzed using Cox multivariate analysis. The effect of early vs. late first thrombosis was also studied. Sixty-six patients were included in the study. Of these, 53 (80%) experienced ≥1 thrombotic event during the study period. Thrombosis led to AVG loss in 26 (39%). The primary patency was 47%, 35%, and 21% at 3, 6, and 12 months, respectively. The assisted primary patency was 50%, 38%, and 25% at 3, 6, and 12 months, respectively. The secondary patency rate was 85%, 76%, and 72% at 3, 6, and 12 months, respectively. Thus, poor primary patency rates were observed despite stent graft placement at the VA. In addition, early thrombosis following stent graft placement was associated with worse AVG outcomes.

A Prospective Management Strategy for Heterotaxy Syndrome with Intestinal Rotation Abnormalities: Imaging Does Not Predict Need for Surgery.

PURPOSE: Heterotaxy syndrome (HS) affects right-left anatomical development in 3% of children with congenital heart disease. Commonly, these patients have intestinal rotation abnormalities (IRA) that differ from typical malrotation. In this prospective study, we examine the development of a management pathway, imaging findings, and clinical course of patients with HS and IRA. METHODS: After literature review, a multispecialty focus group designed a pathway for HS. Participants from a single institution were prospectively enrolled from 2016 to 2019. They underwent an abdominal ultrasound and UGI, however timing was variable based on symptoms. Symptomatic IRA was defined as feeding intolerance, bilious or non-bilious vomiting, bloating, severe reflux, and intermittent pain or abdominal distention. Screening for symptoms occurred every three months for the first two years and then annually. RESULTS: 18 participants were followed for a median of 5.0 years. Three clinical categories were identified: 1) asymptomatic, not requiring intestinal surgery, 72.2%, 2) symptomatic with feeding intolerance or failure to thrive requiring gastrostomy placement and diagnostic laparoscopy with Ladd procedure, 16.7%, and 3) symptomatic requiring urgent exploration for suspicion of volvulus, 11.1%. Need for surgery did not necessarily correlate with US and/or UGI findings. CONCLUSIONS: In children with HS and IRA, postnatal imaging did not inform the need for intestinal surgery. Although rare, volvulus or other forms of proximal obstruction can be anticipated, and symptomatic patients should be offered surgical intervention. A multidisciplinary care pathway for patients with HS and IRA can coordinate care and help counsel families on the likelihood of needing intestinal surgery for IRA. LEVEL OF EVIDENCE: Level II. TYPE OF STUDY: Prospective Cohort Study.

Unusually high association of hypertrophic cardiomyopathy and complex heart defects in children with fasciculoventricular pathways.

INTRODUCTION: Fasciculoventricular pathways (FVPs) are rare causes of preexcitation that do not mediate tachycardias. We report a two-center experience of pediatric patients with FVP and an unexpectedly high association of complex congenital heart defects (CHDs), chromosomal anomalies, and hypertrophic cardiomyopathy. METHODS: A retrospective review of the electrophysiology database at two institutions was performed to identify patients with FVP from January 2000 to January 2011. Medical records of these patients were reviewed for clinical history and course, presence of comorbidities, and details of intracardiac electrophysiology (EP) study. RESULTS: A total of 17 patients were identified. The primary indication for EP study was a preexcitation pattern on electrocardiogram. The majority of patients, 12/17 (71%), were found to have associated cardiac and genetic anomalies. Hypertrophic cardiomyopathy was found in 5/17 (29%) patients, with genetic testing in two patients demonstrating the lysosomal-associated membrane protein 2 mutation (Danon syndrome). Underlying complex CHDs were present in 3/17 (18%) patients. One patient (6%) was status post (s/p) cardiac transplant, one patient had hypertension, and another had Trisomy 21. Other electrophysiologic substrates mediating tachycardia were found in 3/17 (18%) patients. Only 5/17 patients (29%) were otherwise healthy with structurally normal hearts. CONCLUSIONS: In this largest reported series of FVP in children, there is an unusually high association of FVP with complex CHDs, chromosomal anomalies, and hypertrophic cardiomyopathy. Any patient with such disorders and manifest preexcitation should be evaluated with a high index of suspicion for a FVP.

Use of a wearable automated defibrillator in children compared to young adults.

BACKGROUND: A wearable automated external defibrillator has been shown to be efficacious in the prevention of sudden death in adults who had a history of cardiac arrest but who did not have a permanent internal cardioverter/defibrillator (ICD) placed. The use of a wearable defibrillator has not been established in the pediatric population. METHODS: We retrospectively reviewed the clinical database for the wearable external defibrillator from ZOLL Lifecor Corporation (Pittsburgh, PA, USA). We compared the use of the wearable defibrillator in patients ≤18 years of age to those aged 19-21 years. RESULTS: There were 81 patients ≤18 years of age (median age = 16.5 years [9-18] and 52% male). There were 103 patients aged 19-21 years (median age = 20 years [19-21] and 47% male). There was no difference between groups in average hours/day or in total number of days the patients wore the defibrillator. In patients ≤18 years of age, there was one inappropriate therapy and one withholding of therapy due to a device-device interaction. In patients aged 19-21 years, there were five appropriate discharges in two patients and one inappropriate discharge in a single patient. CONCLUSION: It is reasonable to consider the wearable automated external defibrillator as a therapy for pediatric patients who are at high risk of sudden cardiac arrest but who have contraindications to or would like to defer placement of a permanent ICD. As there were no appropriate shocks in our patients ≤18 years of age, this study cannot address efficacy of the therapy.

Cryoablation with an 8-mm tip catheter for pediatric atrioventricular nodal reentrant tachycardia is safe and efficacious with a low incidence of recurrence.

BACKGROUND: Cryoablation with 4- and 6-mm tip ablation catheters has been demonstrated to be safe and effective in the treatment of atrioventricular nodal reentrant tachycardia (AVNRT) in pediatric patients, albeit with a higher rate of clinical recurrence. Limited information is available regarding efficacy, mid-term outcomes, and complications related to the use of the 8-mm Freezor Max Cryoablation catheter (Medtronic, Minneapolis, MN, USA) in pediatric patients. METHODS: We performed a retrospective review of all pediatric patients with normal cardiac anatomy who underwent an ablation procedure for treatment of AVNRT using the 8-mm tip Cryoablation catheter at three large pediatric academic arrhythmia centers. RESULTS: Cryoablation with an 8-mm tip catheter was performed in 77 patients for treatment of AVNRT (female n = 40 [52%], age 14.8 +/- 2.2 years, weight 62.0 +/- 13.9 kg). Initial procedural success was achieved in 69 patients (69/76, 91%). Transient second- or third-degree atrioventricular (AV) block was noted in five patients (6.5%). There was no permanent AV block. Of the patients successfully ablated with Cryotherapy, there were two recurrences (2/70, 2.8%) over a follow-up of 11.6 +/- 3.3 months. CONCLUSION: Cryoablation with an 8-mm tip ablation catheter is both safe and effective with a low risk of recurrence for the treatment of AVNRT in pediatric patients.

Cardiac memory in patients with Wolff-Parkinson-White syndrome: noninvasive imaging of activation and repolarization before and after catheter ablation.

BACKGROUND: Cardiac memory refers to a change in ventricular repolarization induced by and persisting for minutes to months after cessation of a period of altered ventricular activation (eg, resulting from pacing or preexcitation in patients with Wolff-Parkinson-White syndrome). ECG imaging (ECGI) is a novel imaging modality for noninvasive electroanatomic mapping of epicardial activation and repolarization. METHODS AND RESULTS: Fourteen pediatric patients with Wolff-Parkinson-White syndrome and no other congenital disease, were imaged with ECGI a day before and 45 minutes, 1 week, and 1 month after successful catheter ablation. ECGI determined that preexcitation sites were consistent with sites of successful ablation in all cases to within a 1-hour arc of each atrioventricular annulus. In the preexcited rhythm, activation-recovery interval (ARI) was the longest (349+/-6 ms) in the area of preexcitation leading to high average base-to-apex ARI dispersion of 95+/-9 ms (normal is approximately 40 ms). The ARI dispersion remained the same 45 minutes after ablation, although the activation sequence was restored to normal. ARI dispersion was still high (79+/-9 ms) 1 week later and returned to normal (45+/-6 ms) 1 month after ablation. CONCLUSIONS: The study demonstrates that ECGI can noninvasively localize ventricular insertion sites of accessory pathways to guide ablation and evaluate its outcome in pediatric patients with Wolff-Parkinson-White syndrome. Wolff-Parkinson-White is associated with high ARI dispersion in the preexcited rhythm that persists after ablation and gradually returns to normal over a period of 1 month, demonstrating the presence of cardiac memory. The 1-month time course is consistent with transcriptional reprogramming and remodeling of ion channels.

Hypertrophic cardiomyopathy with preexcitation: insights from noninvasive electrocardiographic imaging (ECGI) and catheter mapping.

UNLABELLED: Hypertrophic Cardiomyopathy and Preexcitation. INTRODUCTION: Fasciculoventricular pathway has been described as an unusual variant of preexcitation. Electrocardiographic imaging (ECGI) is a novel imaging modality for noninvasive electroanatomic mapping of epicardial activation and repolarization. CASE: We present a case of an 18-year-old male with hypertrophic cardiomyopathy (HCM) and an electrocardiogram (ECG)-based diagnosis of Wolff-Parkinson-White (WPW) syndrome, who underwent a noninvasive ECGI study to image ventricular activation, followed by an electrophysiology study (EPS). The ECGI electroanatomic isochrone map showed early activation of the epicardial aspect of the atrioventricular (A-V) groove and an aberrant posterior-base-to-apex progression of activation in the left ventricular (LV) epicardium. The EPS showed a likely fasciculoventricular pathway (FVP) without any inducible tachycardia. CONCLUSION: While FVP has been described before, this is the first report of detailed quantitative three-dimensional characterization of electrical activation sequence of a heart with this type of preexcitation, using a novel noninvasive imaging modality (ECGI). In spite of abnormal ventricular activation, the EPS demonstrated that the FVP is not capable of supporting reentrant supraventricular tachycardia or rapidly conducted atrial fibrillation.

Markers of coronary sinus accessory pathways in pediatrics.

INTRODUCTION: Coronary sinus accessory pathways (CSAPs), atrioventricular connections formed by the coronary sinus myocardial coat, have been described in adult patients, but not systematically described in pediatric patients. METHODS: Patients who underwent CSAP ablation were compared to patients with right posteroseptal (RPS) pathway ablation (control group) from November 2004 to June 2007. Retrospective reviews of preablation 12-lead electrocardiogram (EKG), fluoroscopic, and intracardiac electrogram data were then performed to identify electrophysiologic markers of CSAP. RESULTS: A total of 23 patients were identified: 13 with CSAP and 10 with RPS pathways. Preablation EKGs demonstrated preexcitation in 8/10 (80%) patients with RPS pathways versus 9/13 (69%) patients with CSAP (P = 0.66). Preexcitation with a negative delta wave in lead II was seen in 5/9 (56%) patients with CSAP versus 0/8 in RPS (P = 0.029), and preexcitation with a positive delta wave in augmented vector right (aVR) was seen in 9/9 (100%) patients with CSAP versus 3/8 (37.5%) with RPS (P = 0.009). Accessory pathway (AP) potentials were seen on the coronary sinus (CS) catheter in 6/13 (46%) of CSAP and in 0 RPS ablations (P = 0.019). Recurrence of tachycardia occurred in 5/13 (38%) of patients with CSAP and 1/10 (10%) of patients with RPS pathways (P = 0.18). CONCLUSIONS: CSAPs should be considered when preablation EKG demonstrates preexcitation with a negative delta wave in lead II and a positive delta wave in aVR, and if an AP potential is seen on the CS catheter. Recurrence of tachycardia postablation or the need for multiple ablations should raise suspicion for a CSAP.

Alternative delivery of a 4Fr lumenless pacing lead in children.

BACKGROUND: The potential advantages of using a 4Fr lumenless pacing lead (3830 SelectSecure, Medtronic Inc, Minneapolis, MN, USA) in children are largely negated due to the large size of the delivery system. Here we describe an innovative, sheath guided, delivery technique using conventional 5F sheaths. METHODS: Transvenous access was obtained via the left cephalic or axillary vein. A 5Fr introducer set with a 45 degrees curved tip (CheckFlo Performer Introducer Set with the Children's Hospital Boston Modification, Cook Medical Inc, Bloomington, IN, USA) was placed over a wire into the right atrium (RA) or right ventricle (RV). The sheath was modified by cutting off the valved end and a SelectSecuretrade mark lead was introduced through the sheath. Rotating the sheath provided steerability and allowed for precise placement of the lead. After successful lead placement, the sheath was removed with a universal sheath splitter. RESULTS: We placed seven atrial and six ventricular leads in eight patients during nine separate cases with this method. Patient ages and weights ranged from 5 to 16 years and 16 to -59 kg respectively. Pacing thresholds were excellent at implant. Leads were placed successfully in all attempts. There were no procedural complications. One patient had leads placed twice; both lead systems were removed for suspected infection. Over short-term follow-up in five patients, lead position and characteristics have remained stable. CONCLUSION: Delivery of the SelectSecure lead in children can be successfully and precisely performed using a modified 5Fr sheath obviating the need for a large steerable delivery system.

A fatal device-device interaction between a wearable automated defibrillator and a unipolar ventricular pacemaker.

We report a fatal device-device interaction between a wearable automated defibrillator (WAD; LifeVest - LifeCor, Inc., Pittsburgh, PA, USA) and a unipolar pacemaker that occurred in an 18-year-old patient listed for cardiac transplantation due to his failing Fontan. The patient developed ventricular tachycardia that was initially detected by the WAD. However, large unipolar pacing artifacts and specific WAD arrhythmia detection algorithms caused the WAD to revert to nonrecognition of the arrhythmia, which lead to the patient's death. We identify likely causes of the failure and suggest methods of preventing such occurrences in the future.

Experience and results during transition from radiofrequency ablation to cryoablation for treatment of pediatric atrioventricular nodal reentrant tachycardia.

BACKGROUND: Cryoablation has emerged as a new, theoretically safer, modality for treating atrioventricular nodal reentrant tachycardia (AVNRT). The purpose of this study is to compare procedural aspects and outcomes during the transition from radiofrequency (RF) ablation to cryoablation for pediatric AVNRT. METHODS: Data were obtained retrospectively from 80 consecutive pediatric patients who underwent AVNRT ablation from 10/2001- 4/2006 (RF n = 42, Cryo n = 38). Statistical analysis was performed using unpaired t-test, chi-square test, and analysis of variance. RESULTS: RF ablations were performed anatomically in NSR while three different mapping techniques were used during cryoablation: ablation during AVNRT (26%), anatomic in NSR (48%), and anatomic with S(1) S(2) pacing (26%). There was no difference in the number or duration of lesions between the three cryo subgroups. Acute success was obtained in 95% of RF and 97% of cryo cases. There was no difference in the number of total, mapping, or full-duration lesions between the RF and cryogroups. Despite accounting for longer cryolesion time, total ablation time (P < 0.001), mapping time (P = 0.002), and full duration lesion time (P < 0.001) were longer in the cryogroup. There was no significant difference in total procedure time; fluoroscopy time was shorter in the cryoablation group (P = 0.049). There was one confirmed recurrence of tachycardia in each group with a 2% recurrence rate. CONCLUSIONS: Cryoablation for treatment of pediatric AVNRT is as safe and efficacious as RF ablation. Although cryolesions are intrinsically longer in duration, total procedure times were not increased and fluoroscopy times were decreased compared to RF.

Cryoablation of accessory pathways in the coronary sinus in young patients: a multicenter study from the Pediatric and Congenital Electrophysiology Society's Working Group on Cryoablation.

INTRODUCTION: This is a multicenter retrospective study evaluating the immediate- and mid-term outcomes of cryoablation of accessory pathways in the coronary sinus in children or in patients with congenital heart disease. METHODS AND RESULTS: Twenty-one patients (median age 13.0 years, range 2-40) from six institutions were included. The accessory pathways were concealed in 11 and manifest in 10. Of 12 patients who had coronary sinus angiography, two had large coronary sinus diverticula, one had a dilated coronary sinus due to a left superior vena cava to coronary sinus, and one had a "pouch" at the mouth of the coronary sinus. Six patients underwent ablation procedures with cryoablation alone, while in the remaining 15 patients, both cryoablation and radiofrequency ablation were utilized. The ablation procedure included left-sided endocardial mapping via a retrograde or transseptal approach in 13 (62%). Procedural success was achieved with cryoablation in the coronary sinus in 15/21 (71%). Four patients (19%) had successful radiofrequency ablation at the right or left posterior septum. Two patients (10%) had unsuccessful procedures. Of the 15 patients with initially successful cryoablation procedures, six (40%) had arrhythmia recurrences at a median of 17 days (range 1-120). Recurrences could not be explained by differences in patient or procedural variables. CONCLUSION: Cryoablation in the coronary venous system in young patients is feasible but associated with a high arrhythmia recurrence rate. Cryoablation techniques and/or equipment need to be improved in order to safely create more permanent lesions in this arrhythmia substrate.

Atrial Fibrillation in Patients with Congenital Heart Disease.

Advances in surgical techniques have led to the survival of most patients with congenital heart disease (CHD) up to their adulthood. During their lifetime, many of them develop atrial tachyarrhythmias due to atrial dilatation and scarring from surgical procedures. More complex defects and palliative repairs are linked to a higher incidence and earlier occurrence of arrhythmias. Atrial fibrillation (AF) is common in patients who have atrial septal defects repaired after age 55 and in patients with tetralogy of Fallot repaired after age 45. Patients with dextrotransposition of the great arteries who undergo Mustard or Senning atrial switch procedures have an increased risk of atrial flutter due to atrial baffle suture lines. Patients with Ebstein's anomaly are also prone to supraventricular tachycardias caused by accessory bypass tracts. Patients with a single ventricle who undergo Fontan palliation are at risk of developing persistent or permanent AF due to extreme atrial enlargement and hypertrophy. In addition, obtaining vascular access to the pulmonary venous atrium can present unique challenges during radiofrequency ablation for patients with a Fontan palliation. Patients with cyanotic CHD who develop AF have substantial morbidity because of limited hemodynamic reserve and a high viscosity state. Amiodarone is an effective therapy for patients with arrhythmias from CHD, but its use carries long-term risks for toxicity. Dofetilide and sotalol have good short-term effectiveness and are reasonable alternatives to amiodarone. Pulmonary vein isolation is associated with better outcomes in patients taking antiarrhythmic medications. Anticoagulants are challenging to prescribe for patients with CHD because of a lack of data that can be extrapolated to this patient population. Surgical ablation is the gold standard for invasive rhythm control in patients with CHD and should be considered at the time of surgical repair or revision of congenital heart defects. When possible, patients with complex CHD should be referred for care to an adult congenital heart disease center of excellence.

Management of transposed arteriovenous fistula swing point stenosis at the basilic vein angle of transposition by stent grafts.

INTRODUCTION: Transposed basilic vein arteriovenous fistulas suffer from stenosis at their basilic angle of transposition (BAT). This lesion exhibits frequent recurrence after angioplasty. The primary goal of this study was to determine the effect of stent-graft placement on BAT lesion- and access-patency. The secondary goals were to determine the frequency of intervention pre- and post-stent placement and stent-associated stenosis. METHODS: Thirty-seven cases had stent-grafts placed at their BAT to manage stenosis. Cases served as their own controls by analyzing their lesion- and access-patency pre- and post-stent placement. Student's t-test was used for analysis of continuous variables. Categorical variables were evaluated by Fisher's exact test. Tests were considered significant when p was ≤0.05. RESULTS: At 6 and 12 months, pre-stent lesion primary patency rates were 29% and 3%, and post-stent were 57% and 40%, respectively. Lesion primary assisted patency rates were 39% and 13%, and post-stent were 91% and 80%, respectively. At 6 and 12 months, pre-stent access primary patency rates were 29% and 3%, and post-stent were 26% and 19%, respectively. Pre-stent primary access assisted patency rates were 36% and 10%, and post-stent were 82% and 75%, respectively. Lesion intervention rates averaged 0.47/month pre-stent and 0.13/month post-stent. Access intervention rate averaged 0.50/month pre-stent, and 0.15/month post-stent. Stent-associated stenosis was seen in 23 cases. CONCLUSIONS: Treatment of BAT stenosis with stent-grafts had positive impact on the target lesion and the dialysis access circuit.

Integration of Hybrid and Single Ventricle Rehabilitation Techniques to Treat a Neonate After Iatrogenic Mitral Injury.

Neonatal critical aortic stenosis is life threatening and requires intervention shortly after birth. Early percutaneous aortic valvuloplasty is generally considered to be an effective way to obtain reliable prograde flow. We describe the integrated use of hybrid, open surgical, and single ventricle rehabilitation techniques to successfully treat a neonate with borderline left-sided cardiac structures, who sustained a complication from balloon aortic valvuloplasty.

Modification to the Fontan procedure for the prophylaxis of intra-atrial reentrant tachycardia: short-term results of a prospective randomized blinded trial.

OBJECTIVES: We evaluated the feasibility, safety, and short-term efficacy of an interventional atrial incision placed at the time of the Fontan operation to reduce the development of intra-atrial reentrant tachycardia. METHODS: This prospective randomized blinded trial was conducted in patients with congenital heart disease undergoing an initial lateral tunnel Fontan. Intervention patients underwent a lateral tunnel Fontan with an interventional atrial incision/cryoablation from the atriotomy to the right atrioventricular annulus. Controls underwent a standard lateral tunnel Fontan. Safety of the intervention was monitored. Short-term efficacy was determined by comparisons of conduction block across the incision area and spontaneous or inducible atrial arrhythmias. RESULTS: There were no significant differences between intervention (n = 21, median 2.4 years, range 0.8-3.9) and controls (n = 21, median 2.7 years, range 1.5-13.9) in age, type of heart disease, surgical parameters, or postoperative outcomes. Safety parameters showed no difference between groups in number or severity of adverse events. Short-term efficacy included evidence of conduction block with a longer conduction time across the incision area in intervention patients (median 97 ms, range 35-160) compared with controls (median 40 ms, range 8-77, P =.0001). No intervention patients had spontaneous or inducible intra-atrial reentrant tachycardia versus 2 controls (0/21 versus 2/21, P = NS). CONCLUSIONS: An interventional atrial incision to reduce intra-atrial reentrant tachycardia in the Fontan operation was feasible and safe. The intervention changed the atrial substrate as shown by an increase in conduction time. Short-term results showed a low incidence of intra-atrial reentrant tachycardia in all patients. Longer follow-up is necessary to assess clinical efficacy.

Combinatorial diversity of fission yeast SCF ubiquitin ligases by homo- and heterooligomeric assemblies of the F-box proteins Pop1p and Pop2p.

BACKGROUND: SCF ubiquitin ligases share the core subunits cullin 1, SKP1, and HRT1/RBX1/ROC1, which associate with different F-box proteins. F-box proteins bind substrates following their phosphorylation upon stimulation of various signaling pathways. Ubiquitin-mediated destruction of the fission yeast cyclin-dependent kinase inhibitor Rum1p depends on two heterooligomerizing F-box proteins, Pop1p and Pop2p. Both proteins interact with the cullin Pcu1p when overexpressed, but it is unknown whether this reflects their co-assembly into bona fide SCF complexes. RESULTS: We have identified Psh1p and Pip1p, the fission yeast homologues of human SKP1 and HRT1/RBX1/ROC1, and show that both associate with Pop1p, Pop2p, and Pcu1p into a ~500 kDa SCFPop1p-Pop2p complex, which supports polyubiquitylation of Rum1p. Only the F-box of Pop1p is required for SCFPop1p-Pop2p function, while Pop2p seems to be attracted into the complex through binding to Pop1p. Since all SCFPop1p-Pop2p subunits, except for Pop1p, which is exclusively nuclear, localize to both the nucleus and the cytoplasm, the F-box of Pop2p may be critical for the assembly of cytoplasmic SCFPop2p complexes. In support of this notion, we demonstrate individual SCFPop1p and SCFPop2p complexes bearing ubiquitin ligase activity. CONCLUSION: Our data suggest that distinct homo- and heterooligomeric assemblies of Pop1p and Pop2p generate combinatorial diversity of SCFPop function in fission yeast. Whereas a heterooligomeric SCFPop1p-Pop2p complex mediates polyubiquitylation of Rum1p, homooligomeric SCFPop1p and SCFPop2p complexes may target unknown nuclear and cytoplasmic substrates.