Electrophysiologic Studies of Jervell, Lange-Nielsen Syndrome

Electrophysiologic Studies of Jervell,

Lange-'Nielsen Syndrome· Km:umasa Hiefima , M.D.; Fumio Suzuki, M.D.; Shutaro Satake, M.D .; and Keifi Ishihara, M.D. EIedropbyBlolollc studies were performed Ia two libIiD& with Je"eD, LanKe-Nielsen syndrome. FJ~troph)'l­ ioIoIJc parameters were alI witbin normal Umilll except for prolonption of ell~tive refractory period of the

Sinee Jervell and Lange-Nielsen' described the

heritable syndrome of prolongation of QT intervals with deaf-mutism (surdocardiac syndrome"), about 60 cases,a including seven in Japan,· have been reported so far. In almost all patients, syncope and sudden death were attributable to ventricular fl.brillation and asystole. However, as far as we know, electrophysiologic studies do not seem to have been performed on the Jervell, Lange-Nielsen syndrome patients. This paper reports the results of electrophysiologic studies in two siblings with the Jervell, LangeNielsen syndrome.

CASE

ventric:ular myocardium. Thill flndlq may .....t one of electrophysioJoak mecban...... anderlylDa QT proIo.... tion, that Js, delayed ventric:ular repolarization.

At four months of age, her mother suspected she might have hearing difficulty. After one year of age, she began to use a hearing aid, but remained mute . At six, she suddenly fell while at play with rapid recovery. She entered a common elementary school In April 1979. On May 23, she experienced a temporary syncopal attaclt during physical education. She was admitted to our university hospital on May 24. Figure 2 shOWI her ECG at rest. Heart rate Is between 60 and 68 beats per minute. Configuration of T waves Is aimilar to ones of her brother (case 1). The ([fc Interval Is also prolonged to 0.79 seconds. There were not any patients with deaf-mutiJm except these siblings In their family. ELECTROPHYSIOLOGIC STUDIES

CAD 1

The propoIltus wu a ten-year-old boy. He wu bom at full term with normal delivery. HiI development wu normal except for dilturbance of ~ of which hiI mother became aware when he was two yean of ap. At that time, he wu said to be deaf-mute by an otoloillt. At four yearI of ap, he IUdden1y fell at play, whereupon

temporary syncopal attaob and clonic ipums of the lep were observed. At age of seven, while he wu awfJmnini In a pool, I)'Dcopal attacb with clonic ipUDll recurred. Five da)'l later, and abo at age of eight, Iimflar attacb occurred while awImmIng, and he was taken to a university hospital. Since then, phenytoin was adminiatered, although DO abDOI'JDa1ity was observed on hiI EEGs . He was admitted on June 19, 1979, to the Department of Pediatrics of Tokyo Medical and Dental University for close

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Figure 1 shows his ECG at rest In which sinus bradycardia (rates between 55 and 60 per minute) and prolonged ([f interval «([fc: 0.7 sec) are shown.

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-The Firat Department of Internal Medicine and the Department of :Pediatrics, School of Medicine, Tokyo Medi-

cal and Dental University, Tokyo, Japan. ManUlCript received January 25; revision accepted May 27. Btprlnt requm.a: rh. HIefhraG. Fim DflptJrlnuml of Intmwl

M«lIcInB, Tolcvo Medical and DentDl UnItlerritv. 5-45 l-chorne, YuJahna, Bunvo-ku, TokrIo, Tapan.

448 HIEJllIA ET AL

CHEST, 79: 4, APRIL, 1981

been described elsewhere.' In brief, three electrode catheters were introduced percutaneously through both femoral veins using fluoroscopic techniques. A quadripolar catheter and two bipolar catheters (each with an interelectrode distance of 10 mm) were used for recording the high right atrial electrogram and stimulating its position, recording the His bundle electrogram, and stimulating the right ventricle, respectively. Extrastimulus during pacing was performed at both the high right atrium and the apex of the right ventricle by using a programmable digital pulse generator (Sanei-Sokki Type 3F-51). The rectangle stimulating pulses were delivered with 2 msec in duration and approximately twice diastolic threshold Intracardiac electrograms and ECGs leads 2 and Vt were displayed on a multichannel oscilloscope and recorded on a four-channel tape system (TEAC R-351F). The records were subsequently reproduced on an eight-channel Siemens-Elema Mingograf 804 at speeds of 100 and 200 mm/sec.

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REsULTS

Electrophysiologic data for the two cases are shown in Table 1. The sinus cycle length was evidently prolonged in both cases, but the sinus recovery time was within normal limits. The parameters of electrophysiologic studies were within normal limits except for the effective refractory period (ERP) of the ventricular myocardium. Values of the ERP were 340 msec in case 1 and 370 msec in case 2, respectively. The ventriculoatrial conduction was intact in case 2 (Fig 3), but absent in case 1. Ventricular tachycardia or fibrillation was never induced during these electrophysiologic studies. DISCUSSION

The two siblings described here are consistent with the Jervell, Lange-Nielsen syndrome because they were deaf-mute and showed characteristic Q-T Table I-EIee'roplayaolDPe Daaa 01 TtoO Pads... * AVN

CL

A,~V,

SRT PA AH HV ERP FRP ERP ERP

Case 1 980-1100 1050

15

60

47

240

480

290

340

Case 2 880-980 1070 20 125 35 220 440 340 370 •All values are in milliseconds. Abbreviations: CL indicates cycle length; SRT, sinus recovery time; PA, an approximation of intraatrial conduction time; AR, an approximation of A-V nodal conduction time; HV, His-Purkinje system conduction time; A, atrium; AVN, atrioventricular node; V, ventricular myocardium; FRP, functional refractory period; and ERP, effective refractory period.

CHEST, 79: 4, APRIL, 1981

F'IG'UBB 3. Refractory study by venbicular extrastimulus in case 2. Each panel shows from top to bottom high rilht atrial electrogram (HRA), and standard electrocardiographic leads V 1 and 2. Cardiac cycle length is 750 msec, S1' V 1 and A signify stimulus, ventricular, and retrosmde rilht atrial electrograml, respectively, of basic drivin,impulae. S" V 2 and AI lignify stimulus, ventricular and retrosrade hisn right atri&l electro grams, respectively, of ventricular telt impu1le. Numbers in each tracing are In milliseconds. , Paper speed 11100 mm/sec.

prolongation associated with syncopal attacks. No other family member has been affected by the Jervell, Lange-Nielsen syndrome as far back as the two generations in the famlly. However, one might have been affectedby the syndrome in generations before this because its inheritance is autosomal recessive.I The mechanism of Q-T prolongationin the JerveD, Lange-Nielsen syndrome involving Romano-Ward syndrome is still unlcnown, although there is increasing evidence that abnormality of the sympathetic nervous system is responsible for Q-T prolongation.I For example, Q-T prolongation was produced by either stimulating the left stellate ganglion or ablating the right one in dogs" and cats.s These results have led to sympathetic ganglionectomy in patients with Q-T prolongation with success in preventing occurrence of ventricular fibrillation. 8,9, l o However, the ganglionectomy did not necessarily restore the Q-T interval to normal." Electrophysiologically, Q-T prolongation is thought to present delayed ventricular repolarization, with which prolongation of the refractory period is also concerned The measured ERP of the ventricular myocardium in our cases was considerJEMLL, LANGE-NIELSEN SYNDROME 447

ably prolonged. as compared with that of Olsson et aIl l and Guss et al.12 The latter authors further demonstrated that the ERP was effected by basic cycle length (BCL) and pacing site. In our cases, basic ventricular pacing was conducted at a slightly faster rhythm than that of sinus, its rate having enhanced moderately in case 1 at the time of the electrophysiologic study. According to them, the magnitude of shortening of the ERP varied from 10 to 65 msec corresponding with that of the shortening of BCL. In addition, they suggested that the ERP was shorter when pacing was conducted at the right ventricular apex than at the right ventricular outRow tract. It does seem reasonable to judge, at all events, that the ERP of the ventricular myocardium in two children with the Jervell, Lange-Nielsen syndrome was truly prolonged, although the determination was canied out at the right ventricular apex, but not at diHerent BCLs. This is the first report of electrophysiologic studies of the Jervell, Lange-Nielsen syndrome. It is said that the Q-T interval is an indirect but easily obtainable and clinically useful measurement of ventricular recovery properties, although the measurement has some limitations.P In our cases, the measured ERP of the ventricular myocardium was much shorter than Q-T interval (QTc at the time of electrophysiologic study; 0.65 sec in case 1 and 0.71 sec in case 2). The exact cause of this discrepancy is not clear. These findings suggest that no such simple relationship exists between ventricular recovery properties and the T wave.P On the. other hand, pathologic studies on patients with the heritable prolongation of Q-T interval, although there were only a few reports,8..,8.1..18 revealed the Purkinje fibers to be spare and to lack the characteristic clear zone and bulge, and a marked enlargement of the subendocardial Purkinje cells and diffuse endocardial elastofibrosis of the ventricle. These findings suggest the possibility that pathologic abnormality of the ventricular myocardium may be responsible for electrophysiologic abnormality resulting in delayed ventricular repolarization. Accordingly, our study may suggest the electrophysiologic counterpart of the pathologic abnormality. In our cases, ECG was neither taken during the syncopal attacks nor was ventricular fibrillation induced during electrophysiologic studies. It does

448 HIEJIMA ET AL

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seem reasonable to assume, however, that ventricular fibrillation was responsible for the syncopal attacks in our cases, because it is common that ventricular tachyarrhythmia cannot be induced by electrophysiologic maneuver.

1 Jervell A, Lange-Nielsen F. Congenital deaf-mutism, functional heart disease with prolongation of Q-T interval and sudden death. Am Heart J 1957; 54:59-68 2 Jervell A, Thingstad R, Endsjo T. The surdo-cardiac syndrome: three new cases of congenital deafness with syncopal attacks and Q-T prolongation in the electrocardiogram. Am Heart J 1966; 72:582-93 3 Schwartz PJ, Periti M, Milliani A. The long Q-T syndrome. Am Heart J 1975; 89:378-90 4 Hashiba K. Hereditary QT prolongation in Japan: genetic analysis and pathologic findings of the conducting system. Jnp Circ J 1978; 42:1133-50 5 Satake S, Hiejima K, Sakamoto Y, et ale Demonstration of bidirectional dual A-V nodal pathways in the same patient. J Electrocardiol 1977; 10:71-76 6 Fraser GR, Froggatt P, James TN. Congenital deafness associated with electrocardiographic abnormalities, fainting attacks and sudden death. Quart J Med 1964; 33: 361-85 7 Yanowitz F, Preston JB, Abildskov JA. Functional distribution of right and left stellate innervation to the ventricles: production of neurogenic electrocardiographic changes by unilateral alteration of sympathetic tone. Circ Res 1966; 18:416-28 8 Schwartz PJ, Malliani A. Electrical alternation of the T -wave: clinical and experimental evidence of its relationship with the sympathetic nervous system and with the long Q-T syndrome. Am Heart J 1975; 89:45-50 9 Moss AJ, McDonald J. Unilateral cervicothoracic sympathetic ganglionectomy for the treabnent of long Q-T interval syndrome. N Engl J Med 1971; 285:903-04 10 Moss AJ, Schwartz PJ. Sudden death and the idiopathic long Q-T syndrome. Am J Med 1979; 66:6-7 11 Olsson B, Brorson L, Harper R, et a1. Estimation of venbicular refractoriness in man by the extra stimulus method. Cardiovasc Res 1977; 11:31-38 12 Cuss SB, Kastor JA, Josephson ME, et ale Human ventricular refractoriness: effects of cycle length, pacing site and atropine. Circulation 1976; 53:450-55 13 Abildskov JA. Adrenergic effects on the QT interval of the electrocardiogram. Am Heart J 1976; 92:210-16 14 Levine SA, Woodworth CR. Congenital deaf-mutism, prolonged Q-T interval, syncopal attacks and sudden death. N Engl J Med 1958; 259:412-17 15 Phillips J, Ichinose H. Clinical and pathologic studies in the hereditary syndrome of a long QT interval, syncopal spells and sudden death. Chest 1970; 58:236-43 16 Moothart RW, Pryor R, Hawley RL, et ale The heritable syndrome of prolonged Q-T interval, syncope, and sudden death: electron microscopic observations. Chest 1976; 70:263-66

CHEST, 79: 4, APRIL, 1981