Edward P. Walsh

Long-Term Survival, Modes of Death, and Predictors of Mortality in Patients With Fontan Surgery

Background— To better define determinants of mortality in patients with univentricular physiology, a database registry was created of patients born in 1985 or earlier with Fontan surgery who were followed up at Children’s Hospital Boston. Methods and Results— A total of 261 patients, 121 of whom (46.4%) were women, had a first Fontan surgery at a median age of 7.9 years: right atrium–to–pulmonary artery connection in 135 (51.7%); right atrium to right ventricle in 25 (9.6%); and total cavopulmonary connection in 101 (38.7%). Over a median of 12.2 years, 76 (29.1%) died, 5 (1.9%) had cardiac transplantation, 5 (1.9%) had Fontan revision, and 21 (8.0%) had Fontan conversion. Perioperative mortality decreased steadily over time and accounted for 68.4% of all deaths. In early survivors, actuarial freedom from death or transplantation was 93.7%, 89.9%, 87.3%, and 82.6% at 5, 10, 15, and 20 years, respectively, with no significant difference between right atrium to pulmonary artery versus total cavopulmonary connection. Late deaths were classified as sudden in 7 patients (9.2%), thromboembolic in 6 (7.9%), heart failure–related in 5 (6.7%), sepsis in 2 (2.6%), and other in 4 (5.2%). Most sudden deaths were of presumed arrhythmic origin with no identifiable predictor. Independent risk factors for thromboembolic death were lack of antiplatelet or anticoagulant therapy (hazard ratio [HR], 91.6; P=0.0041) and clinically diagnosed intracardiac thrombus (HR, 22.7; P=0.0002). Independent predictors of heart failure death were protein-losing enteropathy (HR, 7.1; P=0.0043), single morphologically right ventricle (HR, 10.5; P=0.0429), and higher right atrial pressure (HR, 1.3 per 1 mm Hg; P=0.0016). Conclusion— In perioperative survivors of Fontan surgery, gradual attrition occurs predominantly from thromboembolic, heart failure–related, and sudden deaths.

Ventricular size and function assessed by cardiac MRI predict major adverse clinical outcomes late after tetralogy of Fallot repair

Background: Factors associated with impaired clinical status in a cross-sectional study of patients with repaired tetralogy of Fallot (TOF) have been reported previously. Objectives: To determine independent predictors of major adverse clinical outcomes late after TOF repair in the same cohort during follow-up evaluated by cardiac magnetic resonance (CMR). Methods: Clinical status at latest follow-up was ascertained in 88 patients (median time from TOF repair to baseline evaluation 20.7 years; median follow-up from baseline evaluation to most recent follow-up 4.2 years). Major adverse outcomes included (a) death; (b) sustained ventricular tachycardia; and (c) increase in NYHA class to grade III or IV. Results: 22 major adverse outcomes occurred in 18 patients (20.5%): death in 4, sustained ventricular tachycardia in 8, and increase in NYHA class in 10. Multivariate analysis identified right ventricular (RV) end-diastolic volume Z ⩾7 (odds ratio (OR) = 4.55, 95% confidence interval (CI) 1.10 to 18.8, p = 0.037) and left ventricular (LV) ejection fraction <55% (OR = 8.05, 95% CI 2.14 to 30.2, p = 0.002) as independent predictors of outcome with an area under the receiver operator characteristic curve of 0.850. LV ejection fraction could be replaced by RV ejection fraction <45% in the multivariate model. QRS duration ⩾180 ms also predicted major adverse events but correlated with RV size. Conclusions: In this cohort, severe RV dilatation and either LV or RV dysfunction assessed by CMR predicted major adverse clinical events. This information may guide risk stratification and therapeutic interventions.

Radiofrequency Catheter Ablation for Tachyarrhythmias in Children and Adolescents

Background Although radiofrequency catheter ablation has been used extensively to treat refractory supraventricular tachycardia in adults, few data are available on its safety and efficacy in children and adolescents. We reviewed registry data obtained from 24 centers to evaluate the indications, early results, complications, and short-term follow-up data in young patients who underwent this procedure. Methods Standardized data were submitted for 652 patients who underwent 725 procedures between January 1, 1991, and September 1, 1992. The mean length of follow-up was 13.5 months. Results The median age of the patients was 13.5 years, and 84 percent of them had structurally normal hearts. The initial success rates for ablation of atrioventricular accessory pathways (508 of 615 procedures) and atrioventricular-node reentry (63 of 76 procedures) were both 83 percent. Greater institutional experience in performing ablation in children and location of the accessory pathway in the left free wall correlated with...

A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus

RNA interference (RNAi) is a natural mechanism regulating protein expression that is mediated by small interfering RNAs (siRNA). Harnessing RNAi has potential to treat human disease; however, clinical evidence for the effectiveness of this therapeutic approach is lacking. ALN-RSV01 is an siRNA directed against the mRNA of the respiratory syncytial virus (RSV) nucleocapsid (N) protein and has substantial antiviral activity in a murine model of RSV infection. We tested the antiviral activity of ALN-RSV01 in adults experimentally infected with wild-type RSV. Eighty-eight healthy subjects were enrolled into a randomized, double-blind, placebo-controlled trial. A nasal spray of ALN-RSV01 or saline placebo was administered daily for 2 days before and for 3 days after RSV inoculation. RSV was measured serially in nasal washes using several different viral assays. Intranasal ALN-RSV01 was well tolerated, exhibiting a safety profile similar to saline placebo. The proportion of culture-defined RSV infections was 71.4 and 44.2% in placebo and ALN-RSV01 recipients, respectively (P = 0.009), representing a 38% decrease in the number of infected and a 95% increase in the number of uninfected subjects. The acquisition of infection over time was significantly lower in ALN-RSV01 recipients (P = 0.007 and P = 0.03, viral culture and PCR, respectively). Multiple logistic regression analysis showed that the ALN-RSV01 antiviral effect was independent of other factors, including preexisting RSV antibody and intranasal proinflammatory cytokine concentrations. ALN-RSV01 has significant antiviral activity against human RSV infection, thus establishing a unique proof-of-concept for an RNAi therapeutic in humans and providing the basis for further evaluation in naturally infected children and adults.

Value of Programmed Ventricular Stimulation After Tetralogy of Fallot Repair A Multicenter Study

Background—Studies have consistently shown that ventricular tachycardia (VT) and sudden cardiac death (SCD) complicate the long-term outcome after tetralogy of Fallot repair, yet the diagnostic and predictive value of electrophysiological testing in this population is uncertain. Methods and Results—A multicenter cohort of 252 patients with repaired tetralogy of Fallot undergoing programmed ventricular stimulation was followed up for 18.5±9.6 and 6.5±4.5 years after corrective surgery and electrophysiological testing, respectively. Clinical VT and/or SCD occurred in 24.6%. Sustained monomorphic VT and polymorphic VT were induced in 30.2% and 4.4%. Including polymorphic VT in the definition of inducibility improved sensitivity (66.1±6.0% versus 77.4±5.3%, P = 0.0082) with a marginal reduction in specificity (81.6±2.8% versus 79.5±2.9%, P = 0.0455). Positive and negative predictive values were 55.2±5.3% and 91.5±2.2%. Independent risk factors for inducibility were age at study ≥18 years (OR, 3.3), palpitations (OR, 2.8), prior palliative surgery (OR, 3.1), modified Lown criteria ≥2 (OR, 5.6), and cardiothoracic ratio ≥0.6 (OR, 3.3). Event-free survival rates in noninducible and inducible patients at 1, 5, 10, and 15 years were 97.9%, 92.8%, 89.3%, and 89.3% versus 79.4%, 62.6%, 58.7%, and 50.3%, respectively (P < 0.0001). Both inducible monomorphic VT [relative risk (RR), 5.0; P = 0.0002] and polymorphic VT (RR, 12.9; P < 0.0001) predicted future clinical VT and SCD. In a multivariate analysis, inducible sustained VT was an independent risk factor for subsequent events (RR, 4.7; 95% CI, 1.2 to 18.5; P = 0.0268). Conclusions—Programmed ventricular stimulation is of diagnostic and prognostic value in risk stratifying patients with repaired tetralogy of Fallot. In this patient population, inducible sustained polymorphic VT should not be disregarded as nonspecific.

Results of a multicenter retrospective implantable cardioverter-defibrillator registry of pediatric and congenital heart disease patients.

OBJECTIVES We sought to determine the implications of implantable cardioverter-defibrillator (ICD) placement in children and patients with congenital heart disease (CHD). BACKGROUND There is increasing frequency of ICD use in pediatric and CHD patients. Until recently, prospective registry enrollment of ICD patients was not available, and children and CHD patients account for only a small percentage of ICD recipients. Therefore, we retrospectively obtained collaborative data from 4 pediatric centers, aiming to identify implant characteristics, shock frequency, and complications in this unique population. METHODS Databases from 4 centers were collated in a blinded fashion. Demographic information, implant electrical parameters, appropriate and inappropriate shock data, and complications were recorded for all implants from 1992 to 2004. RESULTS A total of 443 patients were included, with a median age of 16 years (range 0 to 54 years) and median weight of 61 kg (range 2 to 130 kg), with 69% having structural heart disease. The most common diagnoses were tetralogy of Fallot (19%) and hypertrophic cardiomyopathy (14%). Implant indication was primary prevention in 52%. Shock data were available on 409 patients, of whom 105 (26%) received appropriate shocks (mean 4 shocks/patient, range 1 to 29 shocks/patient). Inappropriate shocks occurred in 87 of 409 patients (21%), with a mean of 6 per patient (range 1 to 60), mainly attributable to lead failure (14%), sinus or atrial tachycardias (9%), and/or oversensing (4%). CONCLUSIONS Children and CHD ICD recipients have significant appropriate and inappropriate shock frequencies. Optimizing programming, medical management, and compliance may diminish inappropriate shocks. Despite concerns regarding generator recalls, lead failure remains the major cause of inappropriate shocks, complications, and system malfunction in children. Prospective assessment of ICD usage in this population may identify additional important factors in pediatric and CHD patients.

Transcatheter ablation of ectopic atrial tachycardia in young patients using radiofrequency current.

BackgroundEctopic atrial tachycardia (EAT) is a reversible cause of cardiomyopathy but may be quite difficult to control with conventional therapy. Transcatheter ablation with radiofrequency current was tested as an alternative to medical or surgical treatment of this condition Methods and ResultsTwelve young patients (aged 10 months to 19 years) with drug-resistant EAT were treated with direct transcatheter ablation of the ectopic focus using radiofrequency (RF) energy. All had depressed left ventricular contractility by echocardiographic criteria, involving shortening fractions of 10–26% (median, 20%; normal, 28–35%). The EAT was mapped to the left atrium in seven cases and to the right atrium in five. Local atrial activation at the ectopic site preceded the onset of the surface P wave by 20–60 msec (median, 42 msec). Tachycardia terminated 0.5–13.0 seconds (median, 2.0 seconds) into a successful RF application. The ablation effectively eliminated EAT in 11 of 12 patients (92%), all of whom were discharged in sinus rhythm without medications after a median hospital stay of 48 hours. Ablation was unsuccessful in one patient with diffuse dysplasia of the anterior right atrium, who eventually did well after surgical resection of abnormal atrial tissue. Transient depression of sinus node function was noted in one patient who had successful ablation of an EAT focus in close proximity to the sinus node, although normal sinus node function returned within 72 hours. No other complications were encountered. During follow-up (3–21 months; median, 13 months), one patient had recurrence of a slower and less-sustained EAT that was successfully eliminated at a second ablation session. All others remained in sinus rhythm, and all 12 subjects recovered normal ventricular function ConclusionsRF ablation appears to be a safe and effective therapeutic option for drug-resistant ectopic atrial tachycardia and may be the preferred first-line therapy for those patients with depressed ventricular function.

Arrhythmias in Adult Patients With Congenital Heart Disease

By the time patients with congenital heart disease (CHD) reach adolescence and early adulthood, rhythm status has often become an active issue, if not the central issue, in their cardiac management. For some, arrhythmias are intrinsic to the structural malformation itself, as is the case with Wolff-Parkinson-White syndrome in the setting of Ebstein’s anomaly, or atrioventricular (AV) block in the setting of “congenitally corrected” transposition of the great arteries (L-TGA). For most other CHD patients, arrhythmias represent an acquired condition related to the unique myocardial substrate created by surgical scars in conjunction with cyanosis and abnormal pressure/volume loads of long duration. This review will attempt to address the major rhythm difficulties faced by adults with CHD, concentrating on electrophysiological features that distinguish CHD from more conventional forms of adult heart disease. A listing of specific arrhythmias and commonly associated congenital defects is provided in Table 1 to serve as an outline for the discussion. View this table: TABLE 1. Specific Arrhythmias and Associated Defects in Adults With Congenital Heart Disease As of 2001, there were estimated to be 800 000 adults with CHD living in the United States,1 a number that has grown steadily as more survivors of childhood surgery reach maturity. Of these, roughly 45% are considered to have mild forms of CHD (eg, atrial septal defect, valvar pulmonary stenosis), 40% are classified as having moderate disease (eg, tetralogy of Fallot, Ebstein’s anomaly), and 15% are considered to have complex disease (eg, single ventricle, transposition of the great arteries). Although arrhythmias can develop within any of the 3 subgroups, the incidence is highest for patients in the moderate and severe categories. Tetralogy of Fallot is an instructive example of moderate CHD with a large arrhythmia burden. As many as one third of patients with repaired tetralogy develop symptomatic atrial tachycardias by …

Factors that influence the development of atrial flutter after the fontan operation

OBJECTIVES Atrial flutter is a frequent, potentially fatal complication of the Fontan operation, but risk factors for its development are ill defined. We evaluated clinical features that might predict the development of atrial flutter in patients who had a Fontan operation. METHODS We evaluated 334 early survivors of a Fontan operation done between April 1973 and July 1991 (mean follow-up, 5.0 +/- 3.8 years). Evaluation included electrocardiography, Holter monitor recordings, and chart review. Modifications of the Fontan operation included an extracardiac conduit (n = 43), an atriopulmonary anastomosis (n = 117), or a total cavopulmonary anastomosis (n = 174). Patient, time, and procedure-related variables were analyzed with respect to the development of atrial flutter. RESULTS Atrial flutter was identified in 54 (16%) patients at a mean of 5.3 +/- 4.7 years (range 0 to 19.7 years) after Fontan operation. Atrial flutter developed sooner and was more likely to occur in patients who were older at the time of Fontan operation (12.4 +/- 7.6 vs 6.3 +/- 5.2 years; p < 0.001), had a longer follow-up interval (8.7 +/- 3.9 vs 4.4 +/- 3.4 years; p < 0.001), had a prior atrial septectomy or pulmonary artery reconstruction (p < 0.01), and had worse New York Heart Association class symptoms (p < 0.02). The presence of sinus node dysfunction was associated with a higher incidence of atrial flutter (p < 0.001). Although there was a lower prevalence of atrial flutter in those patients with a total cavopulmonary anastomosis, the follow-up for this group was shorter. Anatomic diagnoses, perioperative hemodynamics, and other previous palliative operations were not associated with an increased incidence of atrial flutter. Multivariate analysis identified age at operation, duration of follow-up, extensive atrial baffling, and type of repair as factors associated with the development of atrial flutter after Fontan operation. CONCLUSION Atrial flutter continues to develop with time after the Fontan operation. Further follow-up is necessary to determine whether a total cavopulmonary anastomosis reduces the incidence of atrial flutter.

Pulmonary Valve Replacement in Tetralogy of Fallot Impact on Survival and Ventricular Tachycardia

Background— Pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (TOF) reduces pulmonary regurgitation and decreases right ventricular (RV) dilation, but its long-term impact on ventricular tachycardia (VT) and mortality is unknown. This study aimed to determine the incidence of death and VT in TOF after PVR and to test the hypothesis that PVR leads to improvement in these outcomes. Methods and Results— A total of 98 patients with TOF and late PVR for RV dilation were identified. Matched control subjects were identified for 77 of these patients; control subjects had TOF with RV dilation but no PVR. Matching was done by age (±2 years) and baseline QRS duration (±30 ms). No significant differences were found in age, QRS duration, type or decade of initial repair, age at TOF repair, or presence of pre-PVR VT between the 2 groups; limited echocardiographic and magnetic resonance imaging data showed no difference in left ventricular function but more RV dilation among PVR patients than control subjects. In the PVR group, 13 events occurred over 272 patient-years. No significant change in QRS duration was seen for any group. Overall 5- and 10-year freedom from death, VT, or both was 80% and 41%, respectively. In the matched comparison, no significant differences were seen in VT, death, or combined VT and/or death (P=0.32, P=0.06 [nearly favoring controls], and P=0.21). Conclusions— This cohort experienced either VT or death every 20 patient-years. In a matched comparison with a similar TOF group, late PVR for symptomatic pulmonary regurgitation/RV dilation did not reduce the incidence of VT or death.