Ablation of the vanishing PVC, facilitated by quantitative morphology-matching software.

BACKGROUND: Ablation of cardiac arrhythmias in children and teenagers often necessitates the use of anesthesia, which can suppress ventricular arrhythmias (VAs), making it difficult to map the site of origin using activation time (AT). Pace mapping, a technique employed to assist with VA origin localization, depends on subjective comparison of paced and targeted QRS morphology. We assessed the utility of a quantitative approach to paced QRS to VA morphology matching using the PaSo software (Carto 3, Biosense Webster), to localize the VA site of origin. METHODS: Twenty-four patients underwent 26 procedures for frequent VAs, 29 for targeted VA. If AT mapping was precluded due to infrequent VA, pace mapping was executed using the PaSo software, after regionalization based on targeted VA QRS morphology. RESULTS: Subjects were aged 1-32 (mean 14 ± 6) years; 10 were male. Heart disease was present in six patients. PVC frequency prior to onset of anesthesia was 15 ± 16/min, decreasing to 0-1 PVC/min in 17 cases prior to ablation. Arrhythmia localization was performed by AT mapping + PaSo (12) or PaSo only (17). Pace mapping exhibited an intraventricular gradient of percent QRS morphology match. Highest achieved QRS match averaged 96 ± 2%. Successful ablation (> 1-month follow-up) was achieved in 24/29 targeted VAs, 11/12 ablated using AT and pace mapping, and 13/17 VA ablated using pace mapping only, P  =  0.29. CONCLUSIONS: (1) Spontaneous VA frequency was markedly reduced following anesthesia, despite catecholamine administration. (2) Notwithstanding the ability to perform AT mapping, successful ablation can still be performed using pace mapping only, facilitated by the PaSo software.

Pediatric Dilated Cardiomyopathy Patients Do Not Meet Traditional Cardiac Resynchronization Criteria.

INTRODUCTION: Cardiac resynchronization therapy (CRT) is an effective device-based intervention for adults with heart failure (HF) with specific indications, based on large, multicenter randomized clinical trials. The criteria for CRT in adult HF include significant symptoms, ventricular systolic dysfunction, prolonged QRS duration, and left bundle branch block (LBBB) pattern on electrocardiogram (ECG). Despite having less data, CRT is also being widely utilized in children with HF. The shortage of evidence-based CRT criteria in pediatrics prompted us to review a cohort of children with dilated cardiomyopathy and evaluate their potential eligibility for CRT using the traditional adult criteria. METHODS: Single-center data of all pediatric patients with dilated cardiomyopathy were extracted from the heart failure registry and retrospectively reviewed. Patients who had at least 2 separate visits that included HF scoring, electrocardiogram, and echocardiogram were included. Patients who were ventricular paced were excluded. RESULTS: Data for 52 patients meeting inclusion criteria were analyzed. The mean ejection fraction was 25% on the first clinical evaluation and 27% on the second visit. No patient and 2 patients met the adult criteria for prolonged QRS on the first and second encounters, respectively. No patients had an LBBB pattern on ECG. CONCLUSIONS: None of the pediatric HF patients in our study met the published Class I criteria for CRT device therapy in adults. These findings suggest that extrapolation of adult HF data to pediatrics is not sufficient for CRT criteria. Specific guidelines for device implantation in children must be based on scientific investigation including pediatric clinical trials.

Radiofrequency catheter ablation of intractable ventricular tachycardia in an infant following arterial switch operation.

A full-term male neonate presented with cyanosis upon delivery and was subsequently diagnosed with d-transposition of the great arteries, ventricular septal defect, and restrictive atrial septal defect. Following initiation of intravenous prostaglandins and balloon atrial septostomy, an arterial switch operation was performed on day 3 of life. The postoperative course was complicated by intractable ventricular tachycardia that was refractory to lidocaine, amiodarone, esmolol, fosphenytoin, and mexiletine drug therapy. Ventricular tachycardia was suppressed with overdrive atrial pacing but recurred upon discontinuation. Seven weeks postoperatively, radiofrequency catheter ablation was performed due to hemodynamically compromising persistent ventricular tachycardia refractory to medical therapy. The ventricular tachycardia was localized to the inferior-lateral right ventricular outlet septum. The procedure was successful without complications or recurrence. Antiarrhythmics were discontinued after the ablation procedure. Seven days after the ablation, a different, slower fascicular rhythm was noted to compete with the infant's sinus rhythm. This was consistent with the preablation amiodarone having reached subtherapeutic levels given its very long half-life. The patient was restarted on oral beta blockers and amiodarone. The patient was subsequently discharged home in predominantly sinus rhythm with intermittent fascicular rhythm.

Cryoablation and angiographic evidence of a concealed right atrial appendage to right ventricle accessory pathway in an infant.

We report a case of successful cryoablation of a concealed accessory pathway from the right atrial appendage to the right ventricle in an infant. A 4-month-old female who had previously undergone successful ablation of a left-sided accessory pathway was taken to the electrophysiology lab due to recurrent supraventricular tachycardia. While in this second supraventricular tachycardia, we found earliest atrial activation in the distal right atrial appendage. Angiography confirmed a connection between right atrial appendage and the right ventricle. Cryoablation at this location promptly terminated the supraventricular tachycardia. Following ablation, there were no further inducible arrhythmias and ventriculo-atrial dissociation was appreciated.

Electrophysiological interventions for treatment of congestive heart failure in pediatrics and congenital heart disease.

Heart failure therapy, while well tested in the adult population, therapeutic interventions are less well defined in the pediatric population. Several treatment strategies are available for the adult patient with heart failure, thought few of these therapies have been proven in children. Morbidity and mortality in the pediatric population with a failing heart is significant, and rhythm management as well as strategies to improve hemodynamics are important in the care of these children. This review will address issues of rhythm management and resynchronization therapy in pediatric and congenital heart disease patients with heart failure.

Ablation of nonautomatic focal atrial tachycardia in children and adults with congenital heart disease.

INTRODUCTION: Nonautomatic focal atrial tachycardia (NAFAT) has been characterized in adults with structurally normal hearts. This article characterizes NAFAT in a population of patients with complex congenital heart disease. METHODS AND RESULTS: Electrophysiologic and electroanatomic mapping data and acute outcomes were reviewed in patients undergoing mapping and ablative procedures for atrial tachycardia at Children's Hospital, Boston, between January 1999 and December 2003. Twenty-two NAFAT foci were identified in 17 patients out of 216 patients studied. Fourteen of these 17 patients had congenital heart disease. The average age of the patients with a NAFAT mechanism was 27 years and there was no gender predilection. The presumptive diagnosis based on clinical grounds and surface ECG assessment in 11 of 17 patients with NAFAT was atrial flutter. None of the 17 patients were suspected of having a NAFAT mechanism by noninvasive assessment. Four of the 10 patients had both NAFAT and macroreentrant atrial tachycardias. NAFAT cycle lengths varied widely (200-680 ms) between patients. Sixteen of the 22 NAFAT foci were mapped to the anatomic right atrium (RA). Acute ablative success was achieved in 17 out of 22 foci (77%). CONCLUSION: NAFAT is relatively uncommon in a pediatric tertiary care setting, and in that setting occurs most often in adults with congenital heart disease. NAFAT is indistinguishable from other forms of atrial tachycardia by noninvasive means and can mimic other forms of atrial tachycardia on electrocardiogram. The foci were predominantly found in the RA and were, in most cases, acutely amenable to catheter ablation therapy.

Radiofrequency catheter ablation of septal accessory pathways in the pediatric age group.

Radiofrequency catheter ablation (RCA) of septal accessory pathways may be technically challenging in children due to the risk of inadvertent atrioventricular (AV) block in the setting of small cardiac dimensions. Outcomes were reviewed for all patients aged < or =19 years with manifest and concealed septal accessory pathways undergoing RCA since 1990 at a single institution. One hundred forty-five procedures were performed in 127 patients (mean age 11.6 years). The number of studies according to accessory pathway location were: anteroseptal (n = 36), midseptal (n = 20), mouth of coronary sinus (n = 40), middle cardiac vein (n = 6), right posteroseptal (n = 21), and left posteroseptal (n = 22). Ablation was deferred for 9 patients (6 anteroseptal and 3 midseptal) in favor of additional pharmacologic trials. Acute success rates for targeted accessory pathways were: anteroseptal (96%), midseptal (94%), mouth of coronary sinus (88%), middle cardiac vein (100%), right posteroseptal (100%), and left posteroseptal (96%). Recurrence rates during follow-up were: anteroseptal (14%), midseptal (12%), mouth of coronary sinus (3%), right posteroseptal (4%), and left posteroseptal (4%). Permanent second or third degree AV block occurred in 4 of 136 RCA attempts (3%), involving 2 anteroseptal and 2 midseptal pathways. In 3 of these 4 cases, a high probability of block was anticipated from prior ablation efforts, prompting pacemaker insertion before or in conjunction with RCA. Thus, in the pediatric age group, acute RCA success rates for septal accessory pathways can exceed 90%. The risks of AV block and accessory pathway recurrence are most relevant to anteroseptal and midseptal pathways. These data may be factored into patient selection and the decision whether to ablate.

Electrophysiologic characterization and postnatal development of ventricular pre-excitation in a mouse model of cardiac hypertrophy and Wolff-Parkinson-White syndrome.

OBJECTIVES: We sought to characterize an animal model of the Wolff-Parkinson-White (WPW) syndrome to help elucidate the mechanisms of accessory pathway formation. BACKGROUND: Patients with mutations in PRKAG2 manifest cardiac hypertrophy and ventricular pre-excitation; however, the mechanisms underlying the development and conduction of accessory pathways remain unknown. METHODS: We created transgenic mice overexpressing either the Asn488Ile mutant (TG(N488I)) or wild-type (TG(WT)) human PRKAG2 complementary deoxyribonucleic acid under a cardiac-specific promoter. Both groups of transgenic mice underwent intracardiac electrophysiologic, electrocardiographic (ECG), and histologic analyses. RESULTS: On the ECG, approximately 50% of TG(N488I) mice displayed sinus bradycardia and features suggestive of pre-excitation, not seen in TG(WT) mice. The electrophysiologic studies revealed a distinct atrioventricular (AV) connection apart from the AV node, using programmed stimulation. In TG(N488I) mice with pre-excitation, procainamide blocked bypass tract conduction, whereas adenosine infusion caused AV block in TG(WT) mice but not TG(N488I) mice with pre-excitation. Serial ECGs in 16 mice pups revealed no differences at birth. After one week, two of eight TG(N488I) pups had ECG features of pre-excitation, increasing to seven of eight pups by week 4. By nine weeks, one TG(N488I) mouse with WPW syndrome lost this phenotype, whereas TG(WT) pups never developed pre-excitation. Histologic investigation revealed postnatal development of myocardial connections through the annulus fibrosum of the AV valves in young TG(N488I) but not TG(WT) mice. CONCLUSIONS: Transgenic mice overexpressing the Asn488Ile PRKAG2 mutation recapitulate an electrophysiologic phenotype similar to humans with this mutation. This includes procainamide-sensitive, adenosine-resistant accessory pathways induced in postnatal life that may rarely disappear later in life.

Implications of ventricular arrhythmia vulnerability during murine electrophysiology studies.

Programmed ventricular stimulation is being performed for the provocation of ventricular arrhythmias in genetically engineered mice. Despite the high level of interest in this area of translational research, little attention has been given to differentiating between selectivity and specificity of induced ventricular tachycardia (VT) in phenotypically normal mice. We aimed to assess factors that may enhance inducibility of VT in wild-type (WT) mice. In vivo intracardiac electrophysiological studies (EPS) were performed in 230 WT mice of 4 strains. An octapolar electrode catheter was inserted into a jugular vein and advanced to the right atrium and ventricle. Baseline ventricular conduction, refractoriness, and arrhythmia inducibility were assessed using programmed electrical stimulation (PES) and burst pacing. We found that nonsustained VT (> or =4 beats) was inducible in 68/230 (30%) mice. Duration of VT was 1.6 +/- 2.4 s, and the longest episode lasted 24 s. VT inducibility differed by strain and age. Ventricular effective refractory period (VERP) was shorter in mice with inducible VT (44 +/- 12 ms) compared with noninducible mice (61 +/- 16 ms, P < 0.001). VERP increased with age (P < 0.001), albeit with strain-related variability. We conclude that nonsustained VT in WT mice is reproducibly inducible and common. Genetic background variability may predispose certain strains to a higher incidence of arrhythmia induction. EPS methods impact prevalence and specificity of inducible VT. Increased VT inducibility was seen with shorter coupling intervals and application of tightly coupled extrastimuli techniques. These factors should be carefully considered when analyzing PES and burst pacing data in murine models to minimize false positives and optimize accuracy.

Transgenic mice overexpressing mutant PRKAG2 define the cause of Wolff-Parkinson-White syndrome in glycogen storage cardiomyopathy.

BACKGROUND: Mutations in the gamma2 subunit (PRKAG2) of AMP-activated protein kinase produce an unusual human cardiomyopathy characterized by ventricular hypertrophy and electrophysiological abnormalities: Wolff-Parkinson-White syndrome (WPW) and progressive degenerative conduction system disease. Pathological examinations of affected human hearts reveal vacuoles containing amylopectin, a glycogen-related substance. METHODS AND RESULTS: To elucidate the mechanism by which PRKAG2 mutations produce hypertrophy with electrophysiological abnormalities, we constructed transgenic mice overexpressing the PRKAG2 cDNA with or without a missense N488I human mutation. Transgenic mutant mice showed elevated AMP-activated protein kinase activity, accumulated large amounts of cardiac glycogen (30-fold above normal), developed dramatic left ventricular hypertrophy, and exhibited ventricular preexcitation and sinus node dysfunction. Electrophysiological testing demonstrated alternative atrioventricular conduction pathways consistent with WPW. Cardiac histopathology revealed that the annulus fibrosis, which normally insulates the ventricles from inappropriate excitation by the atria, was disrupted by glycogen-filled myocytes. These anomalous microscopic atrioventricular connections, rather than morphologically distinct bypass tracts, appeared to provide the anatomic substrate for ventricular preexcitation. CONCLUSIONS: Our data establish PRKAG2 mutations as a glycogen storage cardiomyopathy, provide an anatomic explanation for electrophysiological findings, and implicate disruption of the annulus fibrosis by glycogen-engorged myocytes as the cause of preexcitation in Pompe, Danon, and other glycogen storage diseases.