Chronotropic Competence of the Sinus Node inCongenital Complete Heart Block

Anil Menon, MD, Earl Dean Silverman, MD, Robert Malcolm Gow, MD, andRobert Murray Hamilton, MD

Isolated congenital complete atrioventricular (AV)block is a rare disorder with an estimated incidence

of 1 in 15,000 to 20,000 live births.1 Most cases areassociated with transplacental passage of maternalanti-Ro/La antibodies.2 Prenatal exposure to anti-Roand/or anti-La antibodies may result in permanentcongenital complete heart block in the fetus or neo-nate. Affected children eventually require permanentpacing. Fetal and neonatal deaths occasionally occur.However, many pregnancies include exposure to an-ti-Ro and anti-La antibodies without the developmentof congenital heart block. Although extensive fibrosisof the AV nodal area has been consistently demon-strated, the involvement of the sinus node in thisdisease process has not been well described. Clinicalsinus node dysfunction has not been previously re-ported in children exposed to maternal anti-Ro oranti-La antibodies. We report 2 cases of isolated sinusnode disease in children of mothers with anti-Ro an-tibodies, and the results of exercise assessment ofchronotropic competence of the sinus node in 28 pa-tients with congenital complete AV block.

• • •A newborn with discoid skin lesions of neonatal

lupus was confirmed to have had maternal exposure toanti-Ro and anti-La antibodies. Electrocardiography at5-1/2 weeks of age revealed sinus bradycardia withjunctional escape rhythm and right ventricular hyper-trophy. At 8-1/2 months of age, the rhythm had pro-gressed to extreme sinus bradycardia with a junctionalescape rate of 52 beats/min (Figure 1). Echocardiog-raphy showed a 7-mm secundum atrial septal defectwith right ventricular dilation and paradoxical septalmotion. Electrophysiologic testing at the age of 2years demonstrated a prolonged atrio-Hisian conduc-tion time of 160 ms and a Wenckebach cycle length of480 ms. The infant underwent repair of atrial septaldefect at 2 years of age, as well as placement of anepicardial permanent DDDR pacing system.

The 15-year-old brother of an adolescent withknown congenital complete heart block was referredfor assessment of bradycardia. Holter monitoringdemonstrated frequent sinus bradycardia with junc-tional escape occurring throughout the day. The pa-tient remains asymptomatic and has not received fur-ther treatment. His mother is positive for anti-Roantibody and weakly positive for anti-La antibody.

These case findings prompted us to assess sinusnode function in our patients with “isolated” congen-ital complete heart block. We evaluated all patients(28; age 126 3 years; 12 male children) with isolatedcongenital complete AV block who have had treadmillexercise tests recorded using standard Bruce protocol.The intrinsic atrial rate at peak exercise was manuallymeasured and compared with published normal data.3

Twelve patients had had prior pacemaker insertions (7VVIR, 5 DDDR). Heart rates are expressed asmeans6 1 SD and atrial rates are plotted as a histo-gram.

The exercise tests were terminated mainly becauseof fatigue, at a median of stage 4 (range, stage 1 to 5)and a median endurance time of 10 minutes (range 5to 13). Atrial rate at rest was 826 13 beats/min;ventricular rate at rest was 616 17 beats/min. Ven-tricular rate at peak exercise was 1186 27 beats/min.Intrinsic atrial rates at peak exercise are summarizedin Figure 2 as a histogram. An abnormally low atrialrate at peak exercise was present in 3 patients, despiteexercise to exhaustion. One of these patients, with anatrial rate at peak exercise of 110 beats/min, is theadolescent brother with congenital heart block men-tioned in the second case report above. For the other 2patients with low atrial rate response to exercise, 1mother was Ro positive and the other refused testing.

• • •Extensive attention has been paid to the AV node

in congenital complete AV block. Pathologic serieshave usually found injury and fibrosis of the AVconduction system, but have also occasionally dem-onstrated sinus node hypoplasia. Simultaneous in-volvement of the sinoatrial node has also been foundin patients with congenital heart block during exami-nation of the conduction system at autopsy. Ho andcolleagues4 reported atrial-axis discontinuity in 7 of 8hearts among children born to mothers with anti-Roantibodies. The anticipated area of the AV node wasoccupied by fibrous and adipose tissue. The sinusnode was examined in 7 hearts, of which 4 were wellformed. The other 3 were smaller than usual. Twowere distinctly hypoplastic and comprised a smallcluster of cells around a central nodal artery. In thethird, the hypoplastic sinus node was surrounded byan extensive area of fibrous tissue. Carter and associ-ates5 presented the autopsy findings of a newborn withisolated congenital complete AV block. There wasfibrosis of the AV node and interruption of the AVbundle, in addition to fibrosis and atrophy of thesinoatrial node. Similar findings were reported byJames et al6 in a young woman with complete AVblock.

Lev and co-workers,7 while examining 7 hearts

From the Department of Pediatrics, Divisions of Cardiology and Rheu-matology, The Hospital for Sick Children, and the University ofToronto, Toronto, Ontario, Canada. Dr. Hamilton’s address is: Divi-sion of Cardiology, The Hospital for Sick Children, 555 UniversityAvenue, Room 1503F, Toronto ONM5G 1X8, Canada. E-mail:robert.hamilton@sickkids.on.ca. Manuscript received November 14,1997; revised manuscript received and accepted June 11, 1998.

1119©1998 by Excerpta Medica, Inc. 0002-9149/98/$19.00All rights reserved. PII S0002-9149(98)00569-4

with isolated congenital complete AV block, showedthat the sinoatrial node region had mild infiltrationwith mononuclear cells. The common theme was anabsence or diminution in the connection between theatria and the AV node or bundle. Thus, although thereis consistent involvement of the AV node and peri-nodal area in isolated congenital complete AV block,the extent of involvement of the sinoatrial node is farfrom fully understood. Interestingly, preliminary datafrom a Langendorff rabbit heart exposed to humananti-Ro antibodies has demonstrated sinus node slow-ing in addition to AV conduction abnormalities.8

Our 2 patients suggest that clinical involvement ofthe sinus node occurs in the presence of anti-Ro anti-bodies, both with and without the presence of congen-ital complete AV block. Data in the literature on thechronotropic competence of the sinoatrial node inisolated congenital complete AV block is limited.Several studies have examined the cardiac response toexercise in congenital complete AV block.9–15 There

is general agreement that cardiac en-largement and increased stroke vol-ume are compensatory mechanismsfor the slow ventricular rate. How-ever, only a few studies have exam-ined the atrial response to maximalexercise. Ikkos and Hanson13 studiedthe atrial and ventricular rates at rest,during, and after bicycle ergometerexercise. One of the 11 patientsshowed evidence of sinoatrial exitblock, but atrial rates at submaximalexercise ranged between 160 and185 beats/min in the remaining pa-tients. Taylor and Godfrey10 per-formed bicycle ergometer exercisetesting in 4 patients with congenitalcomplete AV block, 1 with structuralheart disease. In the 3 patients withstructurally normal hearts (1 of

whom had dextrocardia), all showed a progressiveincrease in the atrial rate; however, only 2 showed thesame overall trend seen in normal subjects at allworkloads. In the largest study to date on isolatedcongenital complete AV block,11 exercise data wasobtained in only 10 of 43 patients (23%), and thechronotropic competence of the sinus node was notcommented upon. Cruz and associates15 assessed 5patients (age 7 to 34 years) with congenital completeAV block by exercise testing and found a mildlydiminished median atrial rate at peak exercise (155beats/min).

Although the sinus node is chronotropically com-petent in most patients with isolated congenital com-plete AV block, it appeared to be incompetent in 3 ofour 28 patients (11%). These data are important inchoosing the type of pacing device, lead system, andmode of pacing (DDDR vs VDD). The usual nonin-vasive method of assessing the chronotropic responseof the sinoatrial node is to examine the atrial rate

FIGURE 1. Fifteen-lead electro-cardiogram of an 8-1/2month old with previous neo-natal lupus erythematosus af-fecting skin, as well as anatrial septal defect of moder-ate size. The electrocardio-gram demonstrates markedsinus bradycardia at a rate of52 beats/min, as well as ex-treme 1& AV block.

FIGURE 2. Histogram of atrial rate at peak exercise for 28 patients undergoing exer-cise testing for congenital complete AV block. Three patients demonstrated chrono-tropic incompetence, with atrial rates at peak exercise of only 100, 110, and 150beats/min.

1120 THE AMERICAN JOURNAL OF CARDIOLOGYT VOL. 82 NOVEMBER 1, 1998

response to exercise; this should be performed, ifpossible, before pacemaker placement for congenitalcomplete AV block.

Sinus node disease may be present in some chil-dren with prenatal exposure to anti-Ro or anti-Laantibodies, and may be an additional indication forcardiac pacing. The demonstration of coexistingsinus node disease will influence the choice of pac-ing mode in children requiring it for congenitalheart block.

1. Michaelsson M, Engle MA. Congenital complete heart block: an internationalstudy of the natural history.Cardiovasc Clin1972;4:85–101.2. Scott JS, Maddison PJ, Taylor PV, Esscher E, Scott O, Skinner RP. Connec-tive-tissue disease, antibodies to ribonucleoprotein, and congenital heart block.N Engl J Med1983;309:209–212.3. Cumming GR, Everatt D, Hastman L. Bruce treadmill test in children: normalvalues in a clinic population.Am J Cardiol1978;41:69–75.4. Ho SY, Esscher E, Anderson RH, Michaelsson M. Anatomy of congenitalcomplete heart block and relation to maternal anti-Ro antibodies.Am J Cardiol1986;58:291-294.

5. Carter JB, Blieden JC, Edwards JE. Congenital heart block. Anatomic corre-lations and review of the literature.Arch Pathol1974;97:51–57.6. James TN, St. Martin E, Willis PW3, Lohr TO. Apoptosis as a possible causeof gradual development of complete heart block and fatal arrhythmias associatedwith absence of the AV node, sinus node, and internodal pathways.Circulation1996;93:1424–1438.7. Lev M, Silverman J, Fitzmaurice FM, Paul MH, Cassels DE, Miller RA. Lackof connection between the atria and the more peripheral conduction system incongenital complete atrioventricular block.Am J Cardiol1971;27:481–490.8. Garcia S, Nascimento JH, Bonfa E, Levy R, Oliveira SF, Tavares AV, deCarvalho AC. Cellular mechanism of the conduction abnormalities induced byserum from anti-Ro/SSA-positive patients in rabbit hearts.J Clin Invest1994;93:718–724.9. Thoren C, Herin P, Vavra J. Studies of submaximal and maximal exercise incongenital complete heart block.Acta Paediatr Belg1974;28(suppl):132–143.10. Taylor MR, Godfrey S. Exercise studies in congenital heart block.Br Heart J1972;34:930–934.11. Sholler GF, Walsh EP. Congenital complete heart block in patients withoutanatomic cardiac defects.Am Heart J1989;118:1193–1198.12. Reybrouck T, B. VE, Dumoulin M, Van der Hauwaert LG. Cardiorespiratoryresponse to exercise in congenital complete atrioventricular block.Am J Cardiol1989;64:896-899.13. Ikkos D, Hanson JS. Response to exercise in congenital complete heart block.Circulation 1960;22:583–590.14. Chammas E, Vaksmann G, Kacet S, Rey C, Breviere GM, el Kohen M,Dupuis C. Holter monitoring, exercise test and atropine test in isolated congenitalatrioventricular block in children.Arch Mal Coeur Vaiss1991;84:659–664.15. Cruz LA, da Cruz PD, Pozzan R, Santiago ML, de Oliveira FE, AlbanesiFilho FM. Assessment of third-degree congenital atrioventricular block by ergo-metric tests.Arq Bras Cardiol1991;57:381–384.

Usefulness of Pindolol in Neurocardiogenic SyncopeDemosthenes Iskos, MD, John Dutton, BS, Melvin M. Scheinman, MD, and

Keith G. Lurie, MD

Neurocardiogenic syncope most often occurs as asolitary event that does not warrant subsequent

prophylactic treatment. In some cases recurrent syn-cope interferes with lifestyle and/or poses significantoccupational risks. Pharmacologic agents includinganticholinergics,1 antiarrhythmics (e.g., disopyr-amide),2,3 theophylline,4,5 centrally acting agents (e.g.,serotonin reuptake inhibitors),6,7 a-adrenergic ago-nists,8 andb-adrenergic blockers5,9–11may be helpfulin these cases. In particular,b-adrenergic blockershave been used for the treatment of recurrent neurallymediated syncope. However, the side effects ofbblockade, especially bradycardia at rest, can be both-ersome. In this respect, use ofb blockers with intrinsicsympathomimetic activity (ISA) seems logical, asthey both attenuate the catecholamine-mediated trig-ger for syncope and reduce bradycardia at rest. Weprospectively tested the hypothesis that pindolol, anonselectiveb blocker with ISA, may represent aneffective treatment for patients with neurocardiogenicsyncope.

• • •The study population comprised 31 consecutive

patients referred for evaluation of syncope at a Uni-versity Medical Center. Patients were included in thestudy if they were first diagnosed with neurocardio-genic syncope or had known neurocardiogenic syn-cope, and pharmacologic treatment and/or pacing hadfailed. Enrollment criteria included: (1) a clinical his-tory of syncope, (2) a positive response to head-up tilt(HUT) table testing in the drug-free state (absence ofall cardioactive drugs for$5 half lives), and (3)absence of a contraindication tob-blocker therapy.

Clinical testing was performed as previously de-scribed.12 The tilt protocol used in this study consistedof the patient being positioned at an angle of 60° fromhorizontal for up to 30 minutes.12 If no syncope oc-curred during the 30-minute tilt, sequential right andleft carotid sinus massage (CSM) was performedwhile the patient was upright. Subsequently, edropho-nium 10 mg was administered intravenously, followedby CSM 45 to 60 seconds later.12 If syncope was notinduced within 5 minutes, the table was returned to thehorizontal position. Heart rate and blood pressurewere monitored to ensure return to the baseline values,after which isoproterenol infusion was started at adose of 1mg/min and titrated up to 4mg/min toachieve an approximate 25% increase in heart ratefrom baseline. Once the target heart rate was reached,a 10-minute head-up tilt at 60° was repeated. If syn-cope was again not induced, the study ended.

A test was considered to be positive if the subjectdeveloped syncope or profound presyncope in associ-ation with a significant and abrupt decrease in blood

From the Cardiac Arrhythmia Center, Department of Medicine, Car-diovascular Division, University of Minnesota School of Medicine,Minneapolis, Minnesota; and the Department of Medicine, Universityof California, San Francisco, California. Dr. Lurie’s address is: Car-diac Arrhythmia Center, University of Minnesota School of Medicine,420 Delaware Street SE, UMHC Box 508, Minneapolis, Minnesota55455. Manuscript received December 16, 1997; revised manu-script received and accepted June 5, 1998.

BRIEF REPORTS 1121