Sudden cardiac death and late arrhythmias after the Fontan operation.

OBJECTIVES: We sought to examine the incidence and predictors of arrhythmias and sudden cardiac death (SCD) after Fontan operation. BACKGROUND: Arrhythmias and SCD have been reported following operations for congenital heart disease, but the incidence and risk factors have not been well defined in patients after a Fontan operation. METHODS: We reviewed records of all patients who had a Fontan operation from 1973 to 2012 (n = 1052) at our institution. A questionnaire was mailed to patients who were not known to be deceased at the initiation of the study. Late arrhythmias were classified as bradyarrhythmias or tachyarrhythmias requiring treatment >30 days after operation. RESULTS: We included 996/1052 (95%) patients with no arrhythmia diagnosis prior to Fontan. Overall 10-, 20-, and 30-year freedom from arrhythmias was 71%, 42%, and 24%, respectively. Of 864 patients who survived >30 days after Fontan, 304 (35%) had atrial flutter, 161 (19%) had atrial fibrillation, 108 (13%) had atrial tachycardia, 37 (4%) had reentrant supraventricular tachycardia, 40 (5%) had ventricular tachycardia, and 113 (13%) had sinus node dysfunction. Predictors of late arrhythmias included an atriopulmonary Fontan, age at operation (>16 years) or atrial arrhythmias postoperatively. During follow-up, 52/1052 (5%) patients had SCD, with 51 having documentation available; 8 patients died suddenly within 30 days and the remaining 43 had an average time to SCD of 6.9 ± 6.7 years (median was 3.8 years). Arrhythmias were documented in 28/43 (65%) patients prior to SCD. Predictors of SCD included atrioventricular valve replacement and post-bypass Fontan pressures >20 mm Hg; preoperative sinus rhythm was protective. CONCLUSIONS: Arrhythmias and SCD are significant concerns among Fontan patients and specific risk factors may warrant closer follow-up and earlier consideration for therapy.

Heart transplantation after Fontan: Results from a surgical Fontan cohort.

We performed a retrospective review of outcomes after heart transplantation during long-term follow-up of a surgical cohort of 1138 Fontan patients who were followed at the Mayo Clinic. Follow-up information was obtained from medical records and a clinical questionnaire that was mailed to patients not known to be deceased at the initiation of the study. Forty-four of 1138 Fontan patients with initial or subsequent evaluation at Mayo had cardiac transplantation between 1988 and 2014 (mean age at transplantation was 23.2 ± 12 yr, median was 19.8 yr; mean interval between Fontan and transplantation was 13.0 ± 7.7 yr, median was 13.1 yr). Two patients had combined organ transplantation (one heart-lung, one heart-liver). Twelve of the 44 (27%) patients had PLE prior to transplantation. There was no difference in post-bypass Fontan pressures or incidence of late reoperations for AVV repair/replacement between transplanted and non-transplanted patients. There were 16 (36%) deaths in the transplantation cohort; seven occurred within 30 days of transplantation. Overall one, five, 10, and 15 yr post-transplantation survival was 80%, 72%, 69%, and 55%, respectively. Although this is a challenging group of patients, intermediate-term results suggest that cardiac transplantation remains a reasonable option for patients with a failed Fontan circulation.

Liver Disease in Patients After the Fontan Operation.

We reviewed records of all patients with an initial Fontan operation or revision from 1973 to 2012 at our institution (n = 1,138); 195 patients had postoperative liver data available. Cirrhosis was identified by histopathology or characteristic findings on imaging with an associated diagnosis of cirrhosis by a hepatologist. Of 195 patients with biopsy or imaging, 10-, 20-, and 30-year freedom from cirrhosis was 99%, 94%, and 57%, respectively. There were 40 of 195 patients (21%) diagnosed with cirrhosis (mean age at Fontan 10.7 ± 8 years). On multivariate analysis, hypoplastic left heart syndrome was associated with increased risk of cirrhosis (n = 2 of 16, p = 0.0133), whereas preoperative sinus rhythm was protective (p = 0.009). Survival after diagnosis of cirrhosis was 57% and 35%, at 1, and 5 years, respectively. The cause of death was known for 9 patients (5 multiorgan failure, 2 liver failure, and 2 heart failure). In conclusion, there is an incremental occurrence of cirrhosis after the Fontan, which should be considered when designing follow-up protocols for patients after Fontan operation.

Contraception Practices and Pregnancy Outcome in Patients after Fontan Operation.

OBJECTIVE: The feasibility and safety of pregnancy after the Fontan operation is not well understood. We sought to determine contraception practices and early and late outcomes of pregnancy after the Fontan operation. DESIGN: We performed a retrospective review of medical records to identify women of childbearing age from the Mayo Clinic Fontan database. A follow-up questionnaire was mailed to all patients not known to be deceased at the time of study. Patients with available contraception and pregnancy data were included in the study. RESULTS: Of the 138 women with available contraception data, 44% used no contraception, 12% each used barrier methods, combination hormone therapy or sterilization, 8% used Depo-Provera, 7% had intrauterine devices, 4% had a partner with a vasectomy and 1% used progestin pills. Six women had thrombotic complications (only one using oral contraceptives). Thirty-five women had pregnancy data available. Prior to the Fontan operation there were 10 pregnancies (8 miscarriages, 2 therapeutic abortions, and no live births). After the Fontan operation there were 70 pregnancies resulting in 35 miscarriages (50%), 29 live births (41%), and 6 therapeutic abortions (9%). There were no maternal deaths during pregnancy. During long-term follow up (26 ± 6 years since the Fontan), 1 death, and 1 cardiac transplant occurred. Mean gestational age of the newborns (n = 22/29) was 33.1 ± 4.0 weeks; mean birth weight (n = 20/29) was 2086 ± 770 g. There was 1 neonatal death because of prematurity and two children were born with congenital heart disease (one patent ductus arteriosus and one membranous ventricular septal defect). CONCLUSIONS: Pregnancy after the Fontan operation is associated with a high rate of miscarriages, preterm delivery, and low birth weight. Further studies are needed to identify specific variables influencing risk stratification of pregnancy in this patient population.

Ventricular fibrillation after elective surgery in an adolescent with long QT syndrome.

Congenital long QT syndrome (LQTS) is a potentially lethal but highly treatable channelopathy. Along with multiple risk reduction measures, a recommendation for left sympathetic cardiac denervation therapy and/or implantable cardioverter defibrillator is made for higher risk patients. Despite its relatively common incidence in paediatric patients, there are no formal recommendations regarding perioperative management and discharge criteria for LQTS patients undergoing ambulatory surgery. This report describes a 17-year-old girl, diagnosed with congenital LQTS at 9 years of age, who had an episode of ventricular fibrillation the day after elective ear, nose and throat surgery. Despite several risk factors, she had a same-day dismissal, was not adequately monitored postoperatively and her cardiologists were not notified of her procedure. For the high-risk LQTS patient, we recommend monitoring of perioperative electrolytes and rhythm, postoperative ECG, adequate ß-blockade therapy, avoidance of particular pharmacological agents, consideration of overnight observation and communication with the patient's cardiologist prior to procedure, and at discharge.

40-Year Follow-Up After the Fontan Operation: Long-Term Outcomes of 1,052 Patients.

BACKGROUND: There are limited long-term, single-cohort, follow-up studies available about patients after the Fontan operation. OBJECTIVES: This study sought to determine the long-term outcome of all patients who had a Fontan operation at the Mayo Clinic. METHODS: Records of all patients who had a modified Fontan operation between 1973 and 2012 were reviewed. A follow-up questionnaire was mailed to all patients alive at the time of the study. RESULTS: Overall, 10-, 20-, and 30-year survival for 1,052 patients was 74%, 61%, and 43%, respectively. Factors associated with decreased overall or late survival in multivariate analysis included pre-operative diuretic use, longer cardiopulmonary bypass time, operation prior to 1991, atrioventricular valve (AVV) replacement at the time of Fontan operation, elevated post-bypass Fontan (>20 mm Hg) or left atrial (>13 mm Hg) pressures, prolonged chest tube drainage (>21 days), post-operative ventricular arrhythmias, renal insufficiency, and development of protein-losing enteropathy (PLE). Pre-operative and intraoperative sinus rhythm were associated with improved survival. Long-term survival was similar for patients regardless of ventricular morphology. The most common reoperations were pacemaker insertion/revision in 212 patients (20%), Fontan revision/conversion in 117 patients (11%), and AVV repair/replacement in 66 patients (5%). Clinically significant late atrial or ventricular arrhythmias occurred in 468 patients (44%). Ninety-five patients (9%) developed PLE, and 5-, 10-, and 20-year survival after diagnosis of PLE was 50%, 35%, and 19%, respectively. CONCLUSIONS: As the surgical techniques for the Fontan operation have changed over the last 40 years, survival has improved. However, development of PLE and arrhythmias and the need for reoperation during long-term follow-up pose significant management challenges.

Automated external defibrillator rescues among children with diagnosed and treated long QT syndrome.

BACKGROUND: Long QT syndrome (LQTS) is a potentially lethal yet highly treatable cardiac channelopathy. A comprehensive LQTS-directed treatment program often includes an automated external defibrillator (AED). OBJECTIVE: The purpose of this study was to determine the incidence of AED rescues among children evaluated, risk-stratified, and treated in an LQTS specialty center. METHODS: We performed a retrospective review of the electronic medical records to identify 1665 patients evaluated in our Genetic Heart Rhythm Clinic (1999-2013). Subset analysis was performed on 291 children managed without an implantable cardioverter-defibrillator (ICD). RESULTS: The average age at diagnosis was 8.3 ± 5.7 years with an average. QTc of 463 ± 40 ms (17% ≥500 ms). The represented LQTS genotypes included type 1 (LQT1) in 52%, type 2 (LQT2) in 35%, and type 3 (LQT3) in 7%. During follow-up, 3 of 291 children (1%) had a cardiac arrest with an appropriate AED rescue (2/51 symptomatic, 1/240 asymptomatic). The first AED rescue occurred during exercise in a symptomatic 3-year-old boy with compound LQT1 treated with beta-blocker and videoscopic left cardiac sympathetic denervation (LCSD). The second AED rescue occurred in a remotely symptomatic 14-year-old boy with high-risk LQT2 (QTc >550 ms) on a beta-blocker who previously declined a prophylactic ICD. The third AED rescue involved an asymptomatic 17-year-old girl with LQT3 on mexiletine who collapsed in school. CONCLUSION: An AED should seldom be necessary in an appropriately treated child with LQTS. Nevertheless, despite only 3 AED rescues in more than 1700 patient-years, an AED can be a lifesaving and cost-effective part of an LQTS patient's comprehensive sudden death prevention program.

Cone reconstruction in children with Ebstein anomaly: the Mayo Clinic experience.

OBJECTIVE: Valve repair for pediatric patients with Ebstein anomaly has historically yielded varied results. The cone reconstruction (CR) first described by Da Silva has revolutionized the surgical approach to these patients. This study reports our recent experience with CR in children and young adults with Ebstein anomaly. DESIGN: Electronic medical records were reviewed for all patients < 21 years old who had surgery to repair Ebstein anomaly at Mayo Clinic Rochester between June 2007 and December 2012. Clinical data including preoperative demographics, intraoperative procedures, and postoperative outcomes were recorded. RESULTS: Eighty-four patients initially had a cone reconstruction (54% male, mean age 10.1 ± 5.9 years). Indications for operation included cardiomegaly (42%), cyanosis (19%), and heart failure (19%). The preoperative echocardiogram demonstrated severe tricuspid regurgitation in 91% of patients. There was one early death and 3 early CR breakdowns requiring reoperation (2 re-repair, 1 tricuspid replacement). Eighty-two patients (98%) had successful CR at the time of hospital discharge. Patient age, gender, cardiopulmonary bypass time, and aortic cross-clamp time were not associated with early CR failure. Use of a partial or eccentric annuloplasty ring correlated with successful initial CR (P = .01). There have been no early CR breakdowns since 2010. Follow-up information was available for 77 patients (longest follow-up 6.5 years; mean 0.8 ± 0.2 years). The most recent postoperative echocardiogram demonstrated mild or no tricuspid regurgitation in 83%. Tricuspid stenosis (mean gradient > 5 mm Hg) was present in 6 patients. There was one late death (motor vehicle accident) and one late re-repair of the tricuspid valve 4 years after initial operation. CONCLUSIONS: CR in children and young adults with Ebstein anomaly can be performed with low early mortality and excellent durability at short-term follow-up. CR represents an important surgical option for young patients. It is applicable to patients with a broad range of anatomic variability and precludes valve replacement in the vast majority. CR should be considered prior to the deleterious effects of chronic right ventricular volume overload and the development of systolic dysfunction, which hamper long-term prognosis. Therefore, early referral for surgical evaluation is recommended.

Empiric treatment of protracted idiopathic purpura fulminans in an infant: a case report and review of the literature.

INTRODUCTION: Idiopathic purpura fulminans is a cutaneous thrombotic disorder usually caused by autoimmune-mediated protein C or S deficiency. This disorder typically presents with purpura and petechiae that eventually slowly or rapidly coalesce into extensive, necrotic eschars on the extremities. We present the first known case of idiopathic purpura fulminans consistent with prior clinical presentations in the setting of a prothrombotic genetic mutation, but without hallmark biochemical evidence of protein C or protein S deficiency. Another novel feature of our patient's presentation is that discontinuation of anti-coagulation has invariably led to recurrence and formation of new lesions, which is unexpected in idiopathic purpura fulminans because clearance of autoimmune factors should be followed by restoration of anti-coagulant function. Although this disease is rare, infants with suspected idiopathic purpura fulminans should be rapidly diagnosed and immediately anti-coagulated to prevent adverse catastrophic outcomes such as amputation and significant developmental delay. CASE PRESENTATION: A six-month-old Caucasian boy was brought to our pediatric hospital service with a low-grade fever and subacute, symmetric, serpiginous, stellate, necrotic eschars on his forearms, legs and feet that eventually spread non-contiguously to his toes, thighs and buttocks. In contrast to his impressive clinical presentation, his serologic evaluation was normal, and he was not responsive to corticosteroids and antibiotics. Full-thickness skin biopsies revealed dermal vessel thrombosis, leading to a diagnosis of idiopathic purpura fulminans and successful treatment with low-molecular-weight heparin, which was transitioned to warfarin. Long-term management has included chronic anti-coagulation because of recurrence of lesions with discontinuation of treatment. CONCLUSION: In infants with necrotic eschars, it is important to first consider infectious, inflammatory and hematologic etiologies. In the absence of etiology for protracted idiopathic purpura fulminans, management should include tissue biopsy, in which thrombotic findings warrant a trial of empiric anti-coagulation. Some infants, including our patient, may need long-term anti-coagulation, especially when the underlying etiology of coagulation remains unidentified and symptoms recur when treatment is halted. Given that our patient still requires anti-coagulation, he may have a yet to be identified autoimmune-mediated mechanism for his truly idiopathic case of protracted purpura fulminans.

Sudden infant death syndrome-associated mutations in the sodium channel beta subunits.

BACKGROUND: Approximately 10% of sudden infant death syndrome (SIDS) cases may stem from potentially lethal cardiac channelopathies, with approximately half of channelopathic SIDS involving the Na(V)1.5 cardiac sodium channel. Recently, Na(V) beta subunits have been implicated in various cardiac arrhythmias. Thus, the 4 genes encoding Na(V) beta subunits represent plausible candidate genes for SIDS. OBJECTIVE: This study sought to determine the spectrum, prevalence, and functional consequences of sodium channel beta-subunit mutations in a SIDS cohort. METHODS: In this institutional review board-approved study, mutational analysis of the 4 beta-subunit genes, SCN1B to 4B, was performed using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing of DNA derived from 292 SIDS cases. Engineered mutations were coexpressed with SCN5A in HEK 293 cells and were whole-cell patch clamped. One of the putative SIDS-associated mutations was similarly studied in adenovirally transduced adult rat ventricular myocytes. RESULTS: Three rare (absent in 200 to 800 reference alleles) missense mutations (beta3-V36M, beta3-V54G, and beta4-S206L) were identified in 3 of 292 SIDS cases. Compared with SCN5A+beta3-WT, beta3-V36M significantly decreased peak I(Na) and increased late I(Na), whereas beta3-V54G resulted in a marked loss of function. beta4-S206L accentuated late I(Na) and positively shifted the midpoint of inactivation compared with SCN5A+beta4-WT. In native cardiomyocytes, beta4-S206L accentuated late I(Na) and increased the ventricular action potential duration compared with beta4-WT. CONCLUSION: This study provides the first molecular and functional evidence to implicate the Na(V) beta subunits in SIDS pathogenesis. Altered Na(V)1.5 sodium channel function due to beta-subunit mutations may account for the molecular pathogenic mechanism underlying approximately 1% of SIDS cases.