Kearns-Sayre Syndrome: Association with Long QT Syndrome?AHMAD RASHID, M.D., and MICHAEL H. KIM, M.D.*

From the Department of Internal Medicine and the *Cardiovascular Division, Washington University in St. Louis, St. Louis, Missouri

Kearns-Sayre Syndrome. Kearns-Sayre syndrome has associated cardiac � ndings, predominantlycomplete heart block, which has been implicated as a mechanism of sudden death in these individuals. Apatient with Kearns-Sayre syndrome who had syncope and multiple cardiac arrests due to ventriculartachycardia in the setting of QT prolongation is described. Long QT syndrome is implicated as anotherpossibility for sudden death in Kearns-Sayre syndrome. This potential association is unexplained, but nowtotals two reports in the small numbers of patients reported. (J Cardiovasc Electrophysiol, Vol. 13, pp.184-185, February 2002)

Kearns-Sayre syndrome, long QT syndrome, sudden death, ventricular tachycardia

Introduction

Kearns-Sayre syndrome originally was described in1958. It is characterized by the triad of progressive externalophthalmoplegia, atypical pigmentary retinopathy, andheart block.1 The pathologic � ndings consist of mitochon-drial abnormalities on electron microscopy and ragged redmuscle � bers that seem to contain excessive amounts ofsuch abnormal mitochondria.2 These abnormalities selec-tively involve both the neuromuscular and cardiac conduc-tion systems. Reports of cardiac involvement have focusedon small numbers of patients, with the predominant � ndingof extensive involvement of the His-Purkinje system, whichis manifested by a prolonged HV interval and infranodalblock.3 -5

The progression to complete heart block is variable.Unlike other cardiac conditions, the presence of fascicularor bundle branch block carries a high risk for early, com-plete heart block.3 ,4 Congestive heart failure also has beendescribed.4 ,5

Sudden death in Kearns-Sayre syndrome has been notedin previous reports, with the presumed etiology being com-plete heart block in most episodes.4 Stokes-Adams attacksor syncope also has been a commonly reported � nding inKearns-Sayre syndrome patients with overt cardiac mani-festations.4 Such events again are presumed to be secondaryto heart block. We report the case of a patient with Kearns-Sayre syndrome who developed syncope secondary to poly-morphic ventricular tachycardia in the presence of long QTsyndrome.

Case Report

A 47-year-old woman with Kearns-Sayre syndrome wastransferred to Barnes-Jewish Hospital following an abruptepisode of syncope at home and multiple episodes of ventric-ular tachycardia requiring cardioversion at the referring hos-pital. Her syncopal event was described as a sudden loss ofconsciousness without warning or symptoms while she wasseated in a chair. Her son brie� y performed cardiopulmonary

resuscitation because he noted no breathing or pulse. By thetime the ambulance arrived, she was awake and at baseline.

Kearns-Sayre syndrome had been diagnosed when the pa-tient was 26 years old. Initial presentation was notable forshort stature, ptosis, bilateral ophthalmoplegia, and pigmen-tary retinopathy. A muscle biopsy con� rmed the diagnosiswith ragged red � bers. By the age of 31 years, she had devel-oped left anterior hemiblock, and an asymptomatic episode ofpolymorphic nonsustained ventricular tachycardia was notedon Holter monitor. On electrophysiologic evaluation at thattime, she had a prolonged HV interval of 75 msec and 3 to 4beats of inducible nonsustained ventricular tachycardia. HerQTc interval was 496 msec. A prophylactic, single-chamberpacemaker was placed. An ECG obtained when she was 37years old showed QTc was 500 msec. Over the years, hercondition had deteriorated gradually, such that she was wheel-chair bound due to progressive muscle weakness. The onlymedication she had taken in the past few months was diazepam(Valium) as needed. Family history was negative for longQT syndrome or early sudden death. Physical examina-tion revealed normal vital signs and only the � ndings ofKearns-Sayre syndrome. There were no signi� cant laboratoryabnormalities, speci� cally normal electrolytes and thyroid-stimulating hormone, and no evidence of myocardial infarction.A transthoracic echocardiogram revealed global left ventricu-lar dysfunction with an estimated ejection fraction of 40%.

The presenting 12-lead ECG at the referring hospitalshowed sinus rhythm at 83 beats/min, left-axis deviation, in-complete right bundle branch block with QRS duration of 110msec, and QTc of 520 msec. Subsequent rhythm strips of thepolymorphic ventricular tachycardia on the � rst day of hospi-

Address for correspondence: Michael H. Kim, M.D., Cardiac Electrophys-iology, Burch 300, Evanston Hospital, 2650 Ridge Avenue, Evanston, IL60201. Fax: 847-570-1865.

Manuscript received 23 August 2001; Accepted for publication 15 Novem-ber 2001.

Figure 1. Rhythm strip of polymorphic ventricular tachycardia obtainedbefore treatment.

184 Reprinted with permission fromJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Volume 13, No. 2, February 2002

Copyright ©2002 by Futura Publishing Company, Inc., Armonk, NY 10504-0418

talization showed a short-long-short initiating sequence withQTc of 530 msec (Fig. 1). Following multiple episodes, she wasplaced on intravenous amiodarone and given a small dose ofprocainamide, which was discontinued prior to transfer. Onarrival to our hospital the next day, her QTc was 660 msec(Fig. 2). The amiodarone was discontinued and a beta-blockerwas administered. The pacemaker was found to be functioningappropriately, with a lower rate limit of 60 beats/min. The ratewas increased to 90 beats/min, but several more episodes ofsustained polymorphic ventricular tachycardia occurred thatrequired de� brillation. On the eighth day of hospitalization,her pacemaker was upgraded to an implantable cardioverterde� brillator (ICD) and she was discharged shortly thereafter.QTc on the day of implant (hospital day 8) was 515 msec. Uponreturn to the de� brillator clinic 7 months after ICD placement,she continued to have QT prolongation of 500 msec.

Discussion

This case report highlights another potential etiologicmechanism for syncope or sudden death in patients withadvanced Kearns-Sayre syndrome. The presence of long QTsyndrome and polymorphic ventricular tachycardia have notbeen considered to be a part of the cardiac manifestations ofKearns-Sayre syndrome. The presence of QT prolongationmany years ago, the clear association between QT prolon-gation and polymorphic ventricular tachycardia in the ab-sence of heart block or bradycardia, and QT prolongationupto 7 months after initial presentation strongly argue for thediagnosis of long QT syndrome. We could not de� nitivelyascertain whether the long QT syndrome present in thispatient was inherited or acquired. There was no familyhistory of long QT syndrome, but formal screening of theparents and siblings was not done. The QT prolongationwasnot secondary to medications or electrolyte abnormalities.Thus, the question has to be raised whether this is associ-ated, in any way, with progressive Kearns-Sayre syndrome.In fact, a case of polymorphic ventricular tachycardia in thesetting of complete heart block with a junctional escape of44 beats/min and QTc of 710 msec was reported in a patientwith Kearns-Sayre syndrome and a structurally normalheart, except for complete heart block.6 The current casediffers in that complete heart block was not present soneither the ventricular tachycardia nor the QT prolongation

was bradycardia dependent. In addition, our patient had acardiomyopathy, which has been reported in patients withKearns-Sayre syndrome.4 No myocardial biopsies weretaken to address this issue.

It is possible that our patient had two preexisting condi-tions: Kearns-Sayre syndrome and its cardiologic manifes-tations, and long QT syndrome distinct from Kearns-Sayresyndrome itself. However, given the potential for suddendeath in these individuals, it should not always be presumedthat the risk is predominantly from complete heart block,but consideration should be given to the potential for sig-ni� cant ventricular arrhythmias. This point is important, asthere have been very few patients with the cardiologicmanifestations of Kearns-Sayre syndrome described in theliterature. Thus, it may be reasonable to follow a strategy ofde� brillator implantation in those patients with a prolongedQT interval and only a pacemaker, if indicated, in thosewithout QT prolongation. The association of Kearns-Sayresyndrome and any link to QT prolongation remains unex-plained, but it should be recognized as a potential problem.To our knowledge, this is the second case documenting thisissue in the small numbers of patients reported.

References

1. Kearns TP, Sayre GP: Retinitis pigmentosa, external ophthalmoplegia,and complete heart block. Arch Ophthalmol 1958;60:280-289.

2. Olson W, Engle WK, Walsh GO, Einaugler R: Oculocraniosomaticneuromuscular disease with “ragged-red” � bers: Histochemical andultrastructural changes in limb muscles of a group of patients withidiopathic progressive external ophthalmoplegia. Arch Neurol 1972;26:193-211.

3. Clark DS, Myerburg RJ, Morales A, Befeler B, Hernandez FA, Gel-band H: Heart block in Kearns-Sayre syndrome: Electrophysiologic-pathologic correlation. Chest 1975;68:727-730.

4. Roberts NK, Perloff JK, Kark RAP: Cardiac conduction in the Kearns-Sayre syndrome (a neuromuscular disorder associated with progressiveexternal ophthalmoplegia and pigmentary retinopathy): Report of 2cases and review of 17 published cases. Am J Cardiol 1979;44:1396-1400.

5. Gallastegui J, Hariman RJ, Handler B, Lev M, Bharati S: Cardiacinvolvement in the Kearns-Sayre syndrome. Am J Cardiol 1987;60:385-388.

6. Nakano T, Imanaka K, Uchida H, Isaka N, Takezawa H: Myocardialultrastructure in Kearns-Sayre syndrome. Angiology 1987;38:28-35.

Figure 2. Twelve-lead ECG obtained on admission.

Rashid and Kim Kearns-Sayre Syndrome 185