Dynamic regulation of partner abundance mediates response of reef coral symbioses to environmental change.

Regulating partner abunclance may allow symmotic organisms to mediate interaction outcomes, facilitating adaptive responses to environmental change. To explore the capacity for-adaptive regulation in an ecologically important endosymbiosis, we studied the population dynamics of symbiotic algae in reef-building corals under different abiotic contexts. We found high natural variability in symbiont abundance in corals across reefs, but this variability converged to different symbiont-specific abundances when colonies were maintained under constant conditions. When conditions changed seasonally, symbiont abundance readjusted to new equilibria. We explain these patterns using an a priori model of symbiotic costs and benefits to the coral host, which shows that the observed changes in symbiont abundance are consistent with the maximization of interaction benefit under different environmental conditions. These results indicate that, while regulating symbiont abundance helps hosts sustain maximum benefit in a dynamic environment, spatiotemporal variation in abiotic factors creates a broad range of symbiont abundances (and interaction outcomes) among corals that may account for observed natural variability in performance (e.g., growth rate) and stress tolerance (e.g., bleaching susceptibility). This cost or benefit framework provides a new perspective on the dynamic regulation of reef coral symbioses and illustrates that the dependence of interaction outcomes on biotic and abiotic contexts may be important in understanding how diverse mutualisms respond to environmental change.

Studies in porphyria. I. A defect in the reductive transformation of natural steroid hormones in the hereditary liver disease, acute intermittent porphyria.

A variety of 5beta steroid metabolites derived from hormones natural to man are potent inducers experimentally of delta-aminolevulinate synthetase, the rate-limiting enzyme in porphyrin-heme formation. This mitochondrial enzyme is found at high levels of activity in the livers of patients with the genetic disease, acute intermittent porphyria (AIP). In this study the metabolism of (14)C-labeled testosterone was examined in AIP patients to determine whether there was a disproportionate conversion of the hormone to its 5beta, compared to its 5alpha metabolite. The results indicate that AIP subjects do generate a substantially greater than normal fraction of 5beta metabolite from this steroid; the excessive degree of ring A reduction of testosterone taking place via the 5beta pathway in the porphyric patients averages 350% greater than in the nonporphyric subjects. In one asymptomatic AIP patient the disproportionate generation of 5beta metabolite from the hormone reached a level 10 times the normal mean. Studies with a second (14)C-labeled hormone, dehydroisoandrosterone, whose metabolism in man resembles that of testosterone, confirmed the derangement in reductive transformation of steroids found in the individuals carrying the genetic lesion of AIP. These findings define a new endocrine abnormality in AIP patients and raise the possibility that endogenously derived 5beta steroids may contribute by an induction mechanism to the increased levels of hepatic delta-aminolevulinate synthetase activity found in AIP patients.

Studies in porphyria. II. Evidence for a deficiency of steroid delta-4-5-alpha-reductase activity in acute intermittent porphyria.

Patients with the genetic liver disease, acute intermittent porphyria (AIP), have a defect in the reductive transformation of steroid hormones that is manifest by the disproportionate generation of 5beta-steroid metabolites from precursor hormones. 5beta-steroid metabolites were earlier shown to be potent inducers experimentally of delta-aminolevulinate synthetase (ALAS), the mitochondrial enzyme that is rate-limiting in porphyrin synthesis, and that is found at high levels of activity in the livers of AIP patients. In this report, the basis for the defective steroid metabolism in AIP has been shown, through studies with the (14)C-labeled adrenal hormone 11beta-hydroxy-Delta(4)-androstenedione, to reside in a substantial deficiency of hepatic steroid Delta(4)-5alpha-reductase activity. This enzymic deficiency was found in all seven AIP patients studied, and ranged from 34% to as much as 70% below the mean enzyme activity characterizing normal subjects. The functional consequence of the low levels of 5alpha-reductase activity in AIP is to divert the reductive transformation of certain natural hormones from the 5alpha- to the 5beta-pathway; the latter is the metabolic route through which endogenous steroids having the potential for inducing hepatic ALAS are generated. It is not presently known whether the 5alpha-reductase deficiency in AIP is acquired in some fashion or whether it has partial genetic determinants. It seems probable, however, that this enzymatic abnormality, coupled with the dramatic increase in hormone synthesis that occurs at puberty, may be of major importance in determining clinical expression of the latent gene defect for AIP in many individuals. The 5alpha-reductases for steroid hormones are known to be localized in the endoplasmic reticulum of hepatic cells and the present findings in AIP thus represent the first demonstration that an enzymic component of these membranous structures is functionally abnormal in this hereditary liver disease.

Comparative analysis of the Pocillopora damicornis genome highlights role of immune system in coral evolution.

Comparative analysis of the expanding genomic resources for scleractinian corals may provide insights into the evolution of these organisms, with implications for their continued persistence under global climate change. Here, we sequenced and annotated the genome of Pocillopora damicornis, one of the most abundant and widespread corals in the world. We compared this genome, based on protein-coding gene orthology, with other publicly available coral genomes (Cnidaria, Anthozoa, Scleractinia), as well as genomes from other anthozoan groups (Actiniaria, Corallimorpharia), and two basal metazoan outgroup phlya (Porifera, Ctenophora). We found that 46.6% of P. damicornis genes had orthologs in all other scleractinians, defining a coral 'core' genome enriched in basic housekeeping functions. Of these core genes, 3.7% were unique to scleractinians and were enriched in immune functionality, suggesting an important role of the immune system in coral evolution. Genes occurring only in P. damicornis were enriched in cellular signaling and stress response pathways, and we found similar immune-related gene family expansions in each coral species, indicating that immune system diversification may be a prominent feature of scleractinian coral evolution at multiple taxonomic levels. Diversification of the immune gene repertoire may underlie scleractinian adaptations to symbiosis, pathogen interactions, and environmental stress.

Catheter ablation of accessory pathways, atrioventricular nodal reentrant tachycardia, and the atrioventricular junction: final results of a prospective, multicenter clinical trial. The Atakr Multicenter Investigators Group.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of a temperature-controlled radiofrequency catheter ablation system. METHODS AND RESULTS: The patient population included 1050 patients who had undergone ablation of atrioventricular nodal reentrant tachycardia (AVNRT), an accessory pathway (AP), or the atrioventricular junction (AVJ). Ablation was successful in 996 patients. The probability of success was highest among patients who had undergone ablation of the AVJ, lowest in patients who had undergone ablation of an AP, and in between for patients who had undergone ablation of AVNRT. A major complication occurred in 32 patients. Four variables predicted ablation success (AVJ, AVNRT, or left free wall AP ablation and an experienced center). Four factors predicted arrhythmia recurrence (right free wall, posteroseptal, septal, and multiple APs). Two variables predicted development of a complication (structural heart disease and the presence of multiple targets), and 3 variables predicted an increased risk of death (heart disease, lower ejection fraction, and AVJ ablation). CONCLUSIONS: These findings may serve as a guide to clinicians considering therapeutic options in patients who are candidates for ablation.

Supraventricular arrhythmias in children.

Sudden death may occur in children with supraventricular arrhythmias. Sick sinus syndrome, particularly if associated with tachycardia, may result in sudden death in children who have had open heart surgery and rarely in children with a normal heart. Children with supraventricular tachycardia rarely die. Only those with junctional automatic tachycardia or Wolff-Parkinson-White syndrome have died. Patients with a short anterograde refractory period may be at risk of sudden death. Surgical division of the accessory connection can prevent sudden death. Digitalis may accelerate atrioventricular (AV) conduction in patients with Wolff-Parkinson-White syndrome and, thus, should be used only after testing in the electrophysiology laboratory. Sudden death due to complete AV block should be preventable using pacemakers. Neonates with a ventricular rate less than 55 beats/min or children with a rate less than 45 beats/min should receive pacemaker therapy because of the statistical probability of death or syncope. Ventricular ectopic beats, particularly if frequent or multiform, may be an indication for pacemaker insertion. Patients with surgical complete AV block that persists for more than 7 to 10 days should receive physiologic pacemakers for the prevention of sudden death and hemodynamic benefit.

Resolution of dilated cardiomyopathy after surgical ablation of ventricular tachycardia in a child.

Sustained tachycardia may be associated with dilated cardiomyopathy that may improve after medical management of the tachycardia. Ventricular tachycardia due to an ectopic focus is uncommon in children and rarely presents as congestive heart failure. This report documents that severe dilated cardiomyopathy in a child was caused by sustained ventricular tachycardia and that, after cryoablation of the tachycardia focus, ventricular function rapidly returned to normal.

Transvenous catheter ablation of a right atrial automatic ectopic tachycardia.

A 10 year old patient with right atrial automatic ectopic tachycardia underwent successful transvenous catheter ablation after endocardial mapping. Tachycardia had been present for 7 years before ablation and associated with development of dilated cardiomyopathy. A single 50 J discharge at the point of earliest atrial activation was followed by the establishment of sinus rhythm that remains at 10 months' follow-up. This case represents the first reported successful catheter ablation of an atrial automatic ectopic tachycardia. Specific anatomic factors favoring successful ablation and improvement in technique are discussed.

Wolff-Parkinson-White syndrome and supraventricular tachycardia during infancy: management and follow-up.

The records of 90 patients with Wolff-Parkinson-White syndrome who presented with supraventricular tachycardia in the first 4 months of life were reviewed. Among these, 63% were male. Structural heart disease was present in 20%, most commonly Ebstein's anomaly. All patients presented with a regular narrow QRS tachycardia, and pre-excitation became evident only when normal sinus rhythm was established. Only one infant had atrial flutter and none had atrial fibrillation. Type A Wolff-Parkinson-White syndrome was most common (49%), with heart disease occurring in only 5% of these patients. In contrast, heart disease was identified in 45% of those with type B syndrome. Initially, normal sinus rhythm was achieved in 88% of the 66 infants treated with digoxin with no deaths. Normal sinus rhythm resumed after electrical countershock in 87% of the 15 infants so treated. Maintenance digoxin therapy was used in 85 patients. The Wolff-Parkinson-White pattern disappeared in 36% of the patients. Four infants died of cardiac causes during the mean follow-up period of 6.5 years. Two of these four infants had congenital heart disease; the third, with a normal heart initially, developed ventricular fibrillation and died from a cardiomyopathy considered related to resuscitation. The remaining infant, with a normal heart, died suddenly at 1 month of age. All were receiving digoxin. A wide QRS tachycardia later appeared in three patients, all with heart disease, one of whom died.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of cardiac pacing after the Mustard operation for transposition of the great arteries.

The most frequent complication of the venous redirection (Mustard or Senning) operation for transposition of the great arteries is cardiac arrhythmia. Drug treatment of tachyarrhythmia often worsens bradyarrhythmia. Pacemakers can now treat both arrhythmias. The technique for implantation of pacemakers after redirection for transposition has changed over time from thoracotomy to subxiphoid to transvenous. Atrial pacing is almost always the mode of choice since the electrophysiologic abnormality is sinus node dysfunction with intact atrioventricular conduction. Twenty-nine patients aged 3 to 19 years (mean 9.6) had implantation of a pacemaker a mean of 5.5 years (range 1 to 14) after undergoing the Mustard operation for transposition of the great arteries. Symptoms referable to bradycardia were eliminated in each case. Four patients who received an antitachycardia pacemaker no longer have symptomatic tachycardia. Four patients have required reoperation, three because of lead problems and one because of traumatic erosion of the pacemaker. Pacemakers provide excellent relief of symptoms after the Mustard or Senning operation. Transvenous atrial automatic antitachycardia pacemakers offer the best combination of ease of implantation and symptomatic relief.

Transcatheter ablative techniques for treatment of the permanent form of junctional reciprocating tachycardia in young patients.

Five patients with medically refractory incessant supraventricular tachycardia due to a posterior septal, slowly conducting accessory connection underwent transcatheter closed chest ablative treatment. The tachycardia characteristics were consistent with the permanent form of junctional reciprocating tachycardia. In each patient the ablative attempts resulted in independent interruption of either the anterograde limb (atrioventricular node-His bundle conduction) or the retrograde limb (accessory connection) of the tachycardia circuit. Permanent retrograde pathway ablation was achieved in only one patient and followed separate permanent transcatheter His bundle ablation. In three of the other four patients the ablation attempt caused temporary interruption of retrograde conduction. Each patient had improved control of tachycardia related to the ablation attempt. Of the five patients, four required pacemaker implantation. With further refinements, selective ablation of the retrograde limb of the tachycardia circuit may be possible. This experience confirms the anatomic independence of the anterograde and retrograde limbs of the tachycardia circuit.

Proarrhythmia, cardiac arrest and death in young patients receiving encainide and flecainide. The Pediatric Electrophysiology Group.

The potential for proarrhythmic responses to the class IC sodium channel-blocking drugs encainide and flecainide has not been well described in young patients. Therefore, data were retrospectively collected from 36 institutions regarding 579 young patients who were administered encainide or flecainide for treatment of supraventricular tachycardias (encainide 86 patients, flecainide 369 patients) or ventricular arrhythmias (encainide 21 patients, flecainide 103 patients) to assess the frequency of proarrhythmia, cardiac arrest and death during therapy (adverse events). The two drugs were similar in regard to efficacy (flecainide 71.4%, encainide 59.8%) and rate of proarrhythmic responses (flecainide 7.4%; encainide 7.5%). However, patients receiving encainide more frequently experienced cardiac arrest (encainide 7.5% vs. flecainide 2.3%, p less than 0.05) or died during treatment (encainide 7.5% vs. flecainide 2.1%, p less than 0.05). Detailed data were provided for 44 patients experiencing one or more adverse events. Patient age, previous drug trials, concomitant therapy and days of inpatient monitoring were similar for patients receiving encainide or flecainide. However, echocardiographic left ventricular shortening before treatment was lower among patients receiving encainide (0.23 +/- 0.09) than among those receiving flecainide (0.34 +/- 0.06, p less than 0.05). Plasma drug concentrations were rarely elevated. Cardiac arrest (12 patients) and deaths (13 patients) occurred predominantly among patients with underlying heart disease, particularly among patients receiving flecainide for supraventricular tachycardia (8.3% vs. 0.3%, p less than 0.001). Fifteen patients with an ostensibly normal heart and normal ventricular function experienced proarrhythmia during treatment for supraventricular tachycardia, but only 3 of the 15 had a cardiac arrest or died. The relatively high incidence of adverse events should be considered when contemplating treatment with encainide or flecainide, particularly among patients with underlying heart disease.

Transesophageal echocardiography detects thrombus formation not identified by transthoracic echocardiography after the Fontan operation.

Transesophageal echocardiography demonstrated six instances of venous thrombus formation in the inferior vena cava, right atrium and caval-pulmonary anastomosis region in four children after a modified Fontan operation. Transthoracic surface echocardiography failed to identify these thrombi in five of the six cases because of the posterior location of the thrombus or imaging interference from surgical hardware. These thrombotic episodes occurred 2 days to 5 years after the Fontan operation in children 25 to 168 months of age. Clinical features of compromised cardiac performance with cyanosis or inadequate perfusion were present during four of the six episodes. In two patients, thrombi occurred around transvenous permanent atrial pacing leads. Therapy to eliminate thrombus included surgery (two cases), anticoagulation with warfarin (three cases) and streptokinase thrombolysis (one case). Disappearance of the thrombus was confirmed by transesophageal study in three of the four cases with follow-up echocardiography. Transesophageal echocardiographic demonstration of atrial and pulmonary thrombi that could not be seen by transthoracic imaging suggests that these thrombi occur with greater frequency in patients who have undergone the Fontan operation than was previously suspected.

Cardiomyopathy and myocarditis in children with ventricular ectopic rhythm.

OBJECTIVE: The objective of this study was to evaluate the histologic features of the myocardium in children with abnormal ventricular ectopic rhythm but a structurally normal heart. BACKGROUND: Abnormal ventricular ectopic rhythm in children with a structurally normal heart is an uncommon but serious condition. Previous studies in adults with these findings have shown that approximately 10% have "primary electrical disease" and that 40% to 100% of these have abnormal histologic findings. METHODS: Endomyocardial biopsy samples were obtained prospectively in 33 subjects presenting with ventricular ectopic rhythm but a structurally normal heart by physical examination and noninvasive studies. Biopsy specimens were evaluated for histologic changes consistent with dilated cardiomyopathy or myocarditis and these results were compared with noninvasive and invasive clinical findings. RESULTS: Of the 33 subjects, 16 (48%) had normal myocardial histologic features (Group A), 14 (42%) had changes similar to the histologic features seen with idiopathic dilated cardiomyopathy (Group B) and 3 (9%) had lymphocytic myocarditis (Group C). Presenting clinical symptoms, surface electrocardiograms (ECGs), exercise stress testing and electrophysiologic stimulation tests failed to predict the biopsy results. Twenty-four-hour ambulatory ECGs showed a statistical difference between sustained and nonsustained ventricular tachycardia in Group A versus Group B (p less than 0.007), with Group A having more sustained ventricular tachycardia. Left ventricular function measured by fractional shortening on echocardiography did not differ between groups, but left ventricular end-diastolic dimension was greater in the subjects with abnormal histologic findings (Group B) (p less than 0.03). CONCLUSIONS: These results provide evidence that approximately 50% of children with abnormal ventricular ectopic rhythm but a structurally normal heart may have subclinical cardiomyopathy or unsuspected myocarditis.

Induction of ventricular tachycardia during electrophysiologic study after repair of tetralogy of Fallot.

An association among premature ventricular complexes on routine electrocardiogram, elevated right ventricular systolic pressure and sudden death after repair of tetralogy of Fallot was previously reported. To examine this relation further, noninvasive, hemodynamic and invasive electrophysiologic data were studied in 27 patients who had undergone repair of tetralogy of Fallot 7 months to 21 years (mean 1.75 years) previously. Syncope, which had occurred in four patients, was not significantly related to ventricular arrhythmia on rest electrocardiogram, 24 hour electrocardiogram or treadmill test. All four patients with syncope had either nonsustained (two patients) or sustained (two patients) ventricular tachycardia induced at electrophysiologic study. His bundle to ventricle conduction interval was prolonged in two patients and Q to right ventricular apex interval was prolonged in three of the four patients. All four had abnormal anatomic or hemodynamic findings: two had a right ventricular systolic pressure of 70 mm Hg or more, one had right ventricular dysfunction with tricuspid insufficiency and one a septal aneurysm. The 9 patients with induced nonsustained or sustained ventricular tachycardia were then compared with the 15 patients without induced ventricular arrhythmias. Those with ventricular tachycardia had a greater prevalence of: more complex ventricular arrhythmia on 24 hour electrocardiogram (63 versus 0%, p less than 0.001), long His bundle to ventricle interval (44 versus 0%, p less than 0.001), right ventricular systolic pressure of 70 mm Hg or more (56 versus 0%, p less than 0.01) and reduced right ventricular ejection fraction (33 versus 7%, p less than 0.025). It is concluded that: 1) induction of nonsustained or sustained ventricular tachycardia was associated with a history of syncope; 2) all patients at risk for syncope could not be identified by routine electrocardiogram 24 hour electrocardiogram or treadmill test; 3) hemodynamic alterations may interact with intraventricular conduction abnormalities and predispose to ventricular tachycardia.

Surgical management of refractory supraventricular tachycardia in infants and children.

Sixty-seven children underwent attempted surgical correction of refractory supraventricular arrhythmias using a combination of intraoperative electrophysiologic mapping followed by surgical division or cryoablation of an aberrant conduction pathway or atrial ectopic focus. The patients ranged in age from 4 months to 18 years (mean 11.4 years). Fifty-five patients (82%) had an abnormal conduction pathway crossing the atrioventricular junction (Kent bundle). Thirty-six (65%) of these 55 patients had classic Wolff-Parkinson-White syndrome with a delta wave of pre-excitation on the surface electrocardiogram. Nineteen (35%), however, demonstrated only retrograde conduction across the Kent bundle and had a normal surface electrocardiogram when tachycardia was not present. Kent bundles were isolated to the following locations: right anterior or lateral in 19 (34.5%), left posterior or lateral in 22 (40%), posteroseptal in 10 (18%), anteroseptal in 2 (4%) and both right and left in 2 (4%). Follow-up evaluation of as long as 8 years (mean 34.9 months) has shown seven immediate failures and one late recurrence of arrhythmia (14.5%). Recent refinements in technique and the use of cryoablation for septal aberrant pathways have improved these results. There have been two failures (8%) in the last 25 attempts. Twelve patients underwent surgery for an atrial ectopic focus by the following techniques: cryoablation in seven patients, excision in one patient and both excision and cryoablation in four patients. At a mean follow-up of 16.6 months, there was one late recurrence in the group with an atrial ectopic focus.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of atrial automatic tachycardia by ablation procedures.

Sixteen cases of atrial focus tachycardia are described clinically, electrophysiologically and hemodynamically. In each case multiple attempts at drug treatment (average 2.5 drugs) had failed. After delineation of the electrophysiologic mechanism, the patients were treated by surgical removal or cryoablation or catheter electroablation of the focus. In two of four patients catheter ablation was successful and without complication. Surgical treatment was successful in 13 of 14 patients. Left ventricular function, which had been abnormal in 10 patients, normalized in all but 1 patient whose echocardiographic shortening fraction improved from 10 to 27%. There have been no recurrences in a follow-up period of 6 months to 5 years (mean 2.2 years). It is recommended that any atrial automatic focus tachycardia that produces hemodynamic compromise undergo definitive treatment. Patients with chronic tachycardia rates of more than 140 beats/min should be followed up closely.

New approaches to treatment of incessant ventricular tachycardia in the very young.

It was assumed that the availability of new antiarrhythmic drugs and new surgical techniques might allow medical or nonexcisional surgical treatment in many young children with incessant ventricular tachycardia. Fourteen infants and young children less than 5 years of age were evaluated and treated for incessant ventricular tachycardia. Medical treatment was pursued up to the use of amiodarone with a type Ib or Ic antiarrhythmic drug unless the patient became hemodynamically unstable. Patients underwent surgery when these drug regimens failed or when moderate congestive heart failure was present. Seven patients were successfully treated medically and seven underwent surgical treatment. Of those treated surgically, five had cryothermic lesions and two had excisions. Five of the surgically treated patients required temporary additional medical treatment. Follow-up ranged from 12 to 53 months (mean 28). Eleven of the 14 patients are currently not taking any antiarrhythmic medication. No patient required a pacemaker, none received anticongestive medications and none died.

Neurocardiogenic syncope in children with a normal heart.

OBJECTIVES: The purpose of this study was to review the results of investigation and management of children with syncope and a structurally normal heart. BACKGROUND: Syncope is a common clinical problem and has many etiologies. Autonomic testing and, in particular, the tilt/orthostatic test have helped to positively diagnose neurocardiogenic syncope in a high proportion of such patients. METHODS: Patient case notes and autonomic test charts were reviewed in 162 children aged 1 to 20 years (mean age 12.8 years) with syncope. The autonomic test consisted of orthostatic maneuver, carotid sinus massage, diving reflex, Valsalva maneuver and dose response to intravenous boluses of isoproterenol and phenylephrine. Serum levels of epinephrine and norepinephrine were drawn during the orthostatic test. After confirmation of neurocardiogenic syncope, treatment was begun with fludrocortisone and salt, and beta-adrenergic blocking agents were used as a second line of therapy when indicated. RESULTS: The orthostatic test was positive for neurocardiogenic syncope in 100 patients (62%) and negative in 62 (38%). Patients in the former group were older, were more often female and had a diminished response to carotid sinus massage, a higher Valsalva ratio and a higher supine epinephrine level. Both groups showed an increase in epinephrine and norepinephrine levels at 5 min of standing. In the orthostatic positive group at the time of syncope, norepinephrine levels decreased, whereas epinephrine levels increased. Patients in this group were also more sensitive to the vasodilating effect of isoproterenol but not to its chronotropic effects. Eleven patients had cardioinhibitory syncope (asystole > or = 3 s). Of these, three had pacemaker implantation. Fludrocortisone and salt used in 84 patients in the orthostatic positive group produced resolution of symptoms in 55 patients (65%) and improvement in 14 (17%). Ten patients received beta-blockers, with resolution in four and improvement in four. CONCLUSIONS: Patients with orthostatic test-proved neurocardiogenic syncope show evidence of autonomic dysfunction. They also show beta-adrenergic hypersensitivity. Treatment initiated on the basis of the protocol was associated with amelioration of symptoms in the majority of patients.

Management of atrial flutter after the Fontan procedure.

OBJECTIVES: The purpose of this study was to review the management of atrial flutter occurring after the Fontan procedure. BACKGROUND: Atrial flutter occurs frequently after the Fontan procedure and is often hemodynamically poorly tolerated. METHODS: The patients' charts were reviewed for relevant information. RESULTS: Between 1984 and 1992, 18 patients had atrial flutter after the Fontan procedure. The underlying heart defect was tricuspid atresia in nine, mitral atresia in six and double inlet left ventricle in three. All but three patients had undergone previous palliative surgery. The time interval from Fontan operation to atrial flutter was < 1 day to 16 years (mean 3.7 years). Seven had early atrial flutter before leaving the hospital. Electrophysiologic study in 15 showed sinus node dysfunction in 12. Atrial flutter was inducible in all patients, and 13 had > 1 flutter configuration. Digoxin and a variety of other antiarrhythmic agents (mean 2.7 drugs/patient) were tried with poor results. Only digoxin, amiodarone, flecainide and propafenone showed some benefit when used alone or in combination. Antitachycardia pacemakers were implanted in 16 patients (endocardial 14, epicardial 2) and, with drugs, were useful in 8 (50%). Because atrial flutter was resistant to treatment, right atriectomy was performed in three patients (with benefit in two, one death), successful radiofrequency catheter His bundle ablation in one patient and catheter ablation of atrial flutter in three patients (two failed, one partial success). One patient underwent heart transplantation, and two died suddenly. Another died of complications after an elective epicardial pacemaker replacement procedure. CONCLUSIONS: Atrial flutter after the Fontan procedure is difficult to control. Aggressive drug and antitachycardia pacemaker therapy help about half of the patients. When these measures fail, other options, such as atriectomy, His bundle ablation or catheter ablation of atrial flutter, need consideration. The risk of sudden death justifies the use of such aggressive treatment methods.