Cardiac manifestations of Lyme
dia: A review
K IRAN S N AGI MD , R ITU J OSHI MD , R AN J AN K T HA K UR MD FRCPC FACC
Arrhythmia Service, University Hospital, London, Ontario, and The Department of Medicine, Michigan State University, Lansing, Michigan, USA
Correspondence: Dr RK Thakur, Arrhythmia Service, Thoracic and Cardiovascular Institute, 405 W Greenlawn Avenue, Suite 110, Lansing, MI 48910, USA. Telephone 517-483-7554, fax 517-483-7568, e-mail thakur@pilot.msu.edu Received for publication April 20, 1994. Accepted August 4, 1995RE V IEW
KS N AGI , R J OSHI, RK T HA K UR . Car d iac mani f es t a t ions of Lyme dis e a:A re v iew.Can J Car d iol 1996;12(5):503-506.
OB J EC T IVE: To de s cribe the clini c al fea t ures of car d iac mani f es t a -tions of Lyme dis e a, the most com m on vector-b orne ill n ess in North Amer i ca, which oc c a s ion a lly re s ults in car d iac in v olve m ent.DATA SOURCES: A re v iew of the English- l anguage clini c al lit e ra -ture per t ain i ng to Lyme dis e a and Lyme car d i t is in d exed in MED -LINE from 1975 to 1995.
DATA EX T RAC T ION:Stud i es de s crib i ng di a g n o s is,clini c al fea t ures, treat m ent or out c ome were re v iewed.
DATA SYN T HE S IS:Car d iac com p li c a t ions of Lyme dis e a may oc c ur in up to 8% of pa t ients. Car d iac mani f es t a t ions oc c ur in the early pha of the ill n ess, at a me d ian of 21 days from the on s et of ery t hema mi g rans.Mani f es t a t ions of Lyme car d i t is in c lude atriov -en t ricu l ar block,my o peri c ar d i t is,in t ra v en t ricu l ar con d uc t ion dis -tur b ances, bun d le branch block and con g es t ive heart fail u re.Tem p o r ary car d iac pac i ng may be re q uired in up to a third of cas and com p lete re c ov e ry oc c urs in most (greater than 90%) pa t ients.The over a ll prog n o s is of Lyme car d i t is is very good, al t hough re c ov -ery may be de l ayed and late com p li c a t ions such as di l ated car d io -myo p a t hy may oc c ur.
CON C LU S ION:Lyme dis e a is a tick-b orne spi r o c hetal in f ec t ion caud by Bor r e l ia bur
g d or f eri .Car d iac com p li c a t ions of Lyme dis e a gen e r a lly oc c ur in the early pha and in c lude con d uc t ion sys t em dis t ur b ances,my o peri c ar d i t is and con g es t ive heart fail u re.
Key Words:Bor r el l io s is,Car d i t is,Con g es t ive heart fail u re,Heart block,Lyme car d i t is,Myo c ar d i t is,Peri c ar d i t is,Spi r o c hetal in f ec t ion,Tick-b orne ill n ess
Manifestations cardiaques de la maladie de Lyme : survol
OB J EC T IF :Déc rire les caractér is t iques clin i ques des mani f es t a -tions car d ia q ues de la mala d ie de Lyme, la plus fréquente des mala -dies trans m is par un vecteur en Amé r i q ue du Nord et qui en t raîne, àl’oc c a s ion,des pro b lèmes car d ia q ues.
SOURCES DES DONNÉES :Sur v ol de la litté r a t ure clin i que de langue anglai au su j et de la mala d ie de Lyme et de la cardite de Lyme, fichée sur MED L INE en t re 1975 et 1995.
EX T RAC T ION DES DONNÉES : Les études dé c rivant le di a g n os -tic,les caractér is t iques clin i ques et le traite m ent ou l’évo l u t ion de la mala d ie ont été pas s ées en re v ue.SYN T HÈSE DES DONNÉES : Les com p li c a t ions car d ia q ues de la mala d ie de Lyme sur v i e n n e
nt chez jusqu’à 8 % des pa t ients. Les mani f es t a t ions car d ia q ues sur v i e n n ent en pha préc oce de la mala -die, en moy e nne 21 jours après le dé c lenche m ent de la glos s ite exfo -lia t ive margi n ée. Les mani f es t a t ions de la cardite de Lyme sont en t re autres le bloc auriculo- v entriculaire, la my o pé r i c ardite, les trou b les de la con d uc t ion in t ra v en t ricu l aire, le bloc de branche et l’in s uffi -sance car d ia q ue. Chez jusqu’à un tiers des cas, il peut être né c es s aire d’in s taller un stimu l ateur car d ia q ue tem p o r aire et la plupart des pa -tients (plus de 90 %) ré c upèrent tout à fait. Le pro n ostic global de la cardite de Lyme est très bon, bien que la réc upér a t ion puis être re -tardée et que des com p li c a t ions tar d i v es,comme une myo c ar d io -pathie di l atée puis s ent sur v e n ir.CON C LU S ION :La mala d ie de Lyme est une in f ec t ion àspi r o c hètes trans m is par une tique et causée par Bor r e l ia burg d or f eri .Les com p li c a t ions car d ia q ues de la mala d ie de Lyme sur v i e n n ent gé -né r ale m ent lors de la pha pré c oce et com p ren n ent des trou b les du système de con d uc t ion,la my o pér i c ardite et l’in s uffi s ance car d ia -que.
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L yme dis e a is a tick- b orne ill n ess caud by the spi r o c hete Bor r e l ia burg d or f eri (1-3). It is the most com m only re p orted vector- b orne ill n ess in the United States (1,4). The clini c al cour of Lyme dis e a is gen e r a lly di v ided into early and late phas (1,5,6). Early dis e a may be lim i ted (ery t hema mi g rans and as s o c i a ted signs and symp t oms) or dis s emi n ated (car d iac and/or neu r o l ogi c al in v olve m ent). Late, or chronic, dis e a gen e r a lly af f ects the joints or the nerv o us sys t em (7). The early pha of dis e a mani f ests it s elf af t er an in c u b a t ion pe r iod of three to 32 days (1,8). Car d iac com p li c a t ions of Lyme dis e a gen e r a lly oc c ur in the early dis s emi n ated pha of the ill n ess and con s ist of vary i ng de g rees of atriov e n t ricu l ar block, my -operi c ar d i t is, in t ra v en t ricu l ar con d uc t ion dis t ur b ances or bun d le branch block and con g es t ive heart fail u re (1,9,10). Val -vu l ar in v olve m ent is not char a c t er i s t ic of Lyme dis e a (1).
Lyme car d i t is oc c urs a me d ian of 21 days (range four to 83 days) af t er the on s et of ery t hema mi g rans. Car d iac mani f es -ta t ions have been re p orted in 8% of North Ameri c an pa t ients (9) and 0.3% to 4% of Euro p ean pa t ients with Lyme dis e a (8,11). A re v iew of 105 North Ameri c an and Euro p ean cas of Lyme car d i t is re v ealed that 77% of pa t ients had some de -gree of atriov e n t ricu l ar block, 16% had peri c ar d i t is, 13% had in t ra v en t ricu l ar con d uc t ion dis t ur b ances or bun d le branch block and 13% had heart fail u re (10).
The di a g n o s is of Lyme dis e a may be dif f i c ult to es t ab l ish de f ini t ively be c au car d iac mani f es t a t ions are non s pe c ific and posi t ive r o l ogi c al stud i es do not nec e s s ar i ly prove that car d iac mani f es t a t ions are due to Lyme dis e a. How e ver, Lyme car d i t is should be con s id e red in pa t ients who have the sys t emic fea t ures of the in f ec t ion and as s o c i a ted car d iac in -volve m ent (12). Skin le s ions and fe v er are of t en still pres e nt when car d iac in v olve m ent de v el o ps, and ar t icu l ar and neu r o -logi c al mani f es t a t ions may be pres e nt in many of the pa-tients (1,9). Rarely, com p lete heart block may be the first and the sole mani f es t a t ion of Lyme dis e a (1,13). ELISA or West e rn blot r o l ogi c al analy s is is quite re l i a ble. Im m u n o -globu l in (Ig) M posi t iv i ty sug g ests re c ent in f u s ion, whereas IgG posi t iv i ty sug g ests re m ote in f ec t ion. Se r o l ogi c al tests for Lyme dis e a are of t en nega t ive in the first four to eight weeks and, there f ore, a nega t ive test does not rule out the di a g n o -sis, whereas fal posi t ive rates for r o l ogi c al tests are in the 2% to 4% range. Se r um antibod i es gen e r a lly per s ist long af t er in f ec t ion is cured.Thus, a pa t ient may de v elop heart dis e a un r e l ated to a pre v i o us in f ec t ion, which may fally be at t rib u ted to Lyme car d i t is.
CONDUCTION DISTURBANCES Tran s ient atriov e n t ricu l ar block is the most com m on mani -fes t a t ion of Lyme car d i t is (8-10,14). Lyme dis e a can af f ect the en t ire con d uc t ion sys t e
m but the atriov e n t ricu l ar node is the most sus c ep t i b le to in j ury (10,15). First- d egree atriov e n -tricu l ar block, Wencke b ach block and com p lete atriov e n t ricu -lar block can all oc c ur and may shift rap i dly from one to an o ther(1).Pa t ients with high-d egree atriov e n t ricu l ar block are of t en symp t o m atic with pal p i t a t ions, dysp n ea, subster n al chest pain, diz z i n ess or syn c ope (1,9). In con t rast, pa t ients who have only first- d egree atriov e n t ricu l ar block are gen e r a lly as y mp t o m atic(9).
Com p lete heart block rarely lasts longer than one week and lesr de g rees of heart block are usu a lly re v ersi b le within six weeks (1,9,16). There is of t en a pro g res s ion from com p lete heart block through in t er m e d i a te de g rees of heart block to first- d egree heart block with a gradu a lly de c reas i ng PR in t er v al and ul t i m ately back to nor m al atriov e n t ricu l ar con d uc t ion (8,16). There are, how e ver, ca re p orts of ir r e v ersi b le con d uc -tion sys t em dis t ur b ances (10,11,14,16- 18). Death has also been re p orted (8,10,19,20).
The avail a ble data sug g est that the heart block is at or above the atriov e n t ricu l ar node (1,8,16,21). Elec t ro p hysio l ogi c al stud i es have shown, how e ver, that atriov e n t ricu l ar block can oc c ur at dif f er e nt lev e ls within the con d uc t ion sys t em. Si -noatrial and intra- a trial con d uc t ion dis t ur b ances as well as in f ra n o d al atriov e n t ricu l ar block have been de s cribed (8,1
4,16). Cer t ain fea t ures (es c ape rhythms that are slow and of wide QRS, tran s ient lack of any es c ape rhythm, and fluc t u -at i ng left and right bun d le branch block) sug g est dif f u in -volve m ent of the con d uc t ion sys t em (16,22).
Lyme dis e a must be in c luded in the dif f er e n t ial di a g n o s is of heart block, even if it is not sug g ested by a char a c t er i s t ic his -tory, be c au some pa t ients may pres e nt with only r i o us rhythm dis t ur b ances (14,23).
Pa t ients with high- d egree atriov e n t ricu l ar block or first-d egree heart block with a PR in t er v al longer than 300 ms should be hos p i t al i zed and ob s erved in a te l eme t ry unit be -cau they are at in c read risk of com p lete heart block and asys t ole (1,8,9). Pa t ients with slightly pro l onged PR in t er v als should re s trict their ac t ivi t ies but can be fol l owed as out-p -atients (9). Oral an t i b i o tic ther a py short e ns the du r a t ion of ery t hema mi g rans and as s o c i a ted symp t oms and pre v ents or at t enu a tes late ill n ess in most pa t ients (1,2,5,8,24). The role of an t i b i o t i cs in pre v ent i ng Lyme car d i t is, how e ver, has not been ade q uately as s esd (16,23- 26). It does not ap p ear that early an t i b i o tic ther a py de c reas the du r a t ion of car d iac in v olve -ment (8). The con d uc t ion sys t em dis e a in Lyme car d i t is ap -pears to be re v ersi b le with or with o ut an t i b i o t i cs (27). In fact, Steere et al (9) noted no dif f er e nce in the du
r a t ion or long term prog n o s is of heart block in pa t ients treated with an t i b i o t -ics com p ared with tho who re c eived only anti- i nflammatory drugs. An t i b i o tic ther a py is not an ab s o l ute re q uire m ent for com p lete re c ov e ry of Lyme car d i t is, but should not be with -held be c au of the proven bene f i c ial ef f ects in other mani f es -ta t ions of Lyme bor r e l io s is (10). Predni s one (40 to 60 mg/day in di v ided dos, ta p ered by 5 to 10 mg/week) or sali c y l ates (3.6 g/day in di v ided dos) is rec o m m ended for the treat m ent of pa t ients with Lyme car d i t is in whom high- d egree atriov e n -tricu l ar block, first- d egree heart block with PR in t er v al pro l on -ga t ion greater than 300 ms or car d io m egaly de v el o ps. Predni s one is spe c ifi c ally rec o m m ended for tho with as s o c i -ated men i n g oen c epha l i t is, per s is t ent com p lete heart block last
i ng longer than one week or car
d io
m egaly (9,12,14,22,24,28). The ba s is of this rec o m m en d a t ion, how -ever, is an e c d o t al. Some authors sug g est start i ng predni s one if the heart block does not be g in to re s olve within 24 to 48 h (7).
Nagi et al
A dis a d v an t age of us i ng cor t i c os t er o ids is that two to four months of ther a py may be nec e s s ary be c au of re c ur r ent joint or neu r o l ogi c al symp t oms while the do of the medi c a t ion is be i ng ta p ered (9,12). The heart block of Lyme car d i t is is al -most al w ays lf- l imited, with reso l u t ion usu a lly be g in n ing within a few days. How e ver, in pa t ients with v ere or symp t o -matic heart block, tem p o r ary pac i ng may be nec e s s ary. van d er -Linde (10) re v iewed 105 cas of Lyme car d i t is and noted that tem p o r ary car d iac pac i ng was re q uired in 35%. In d i c a t ions for pac i ng are the same as for other caus of heart block (7). Ade q uate an t i b i o tic ther a py may avoid the need for per m a -nent pace m aker in s er t ion(1,14,16).
MYOPERICARDITIS
In ad d i t ion to con d uc t ion dis t ur b ances, B burg d or f eri can cau in f lam m a t ion of all heart lay e rs.Mani f es t a t ions of Lyme my o peri c ar d i t is, such as dif f u T wave flat t en i ng or in v er s ion, ST g m ent de p res s ion, tran s ient and re v ersi b le de p res s ion of left ven t ricu l ar func t ion, car d io m egaly and peri c ar d i t is, have been noted in up to 65% of pa t ients (8,
29). Most pa t ients, how e ver, have ei t her nor m al left ven t ricu l ar func t ion or only mildly de p resd left ven t ricu l ar func t ion that re s olves (9,15).
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Gallium- 67 myo c ar d ial scan n ing has been docu m ented by a number of authors to show in t en, dif f u up t ake in the myo c ar d ium of at least some pa t ients with Lyme car d i t is (8,14,30- 32). This non s pe c ific test for in f lam m a t ion may be ud to as s ess sus p ected car d iac in v olve m ent in Lyme dis e a (8). Nor m ali z a t ion of gal l ium up t ake par a l l els reso l u t ion of Lyme car d i t is (8). It should be em p ha s ized, how e ver, that clini -cal in v es t i g a t ive aids are in s en s i t ive and non s pe c ific in iden t i -fy i ng pa t ients with Lyme car d i t is (8). In fact, gallium- 67 scin t ig r a p hy and en d o m yo c ar d ial bi o psy are not es s en t ial to the di a g n o s is of Lyme car d i t is.
The his t ol o gy of Lyme car d i t is most com m only shows a trans m u r al in f lam m a t ory in f il t rate. The en d o c ar d ial zone is af f ected by a char a c t er i s t ic band-l ike in f il t rate of plasma cells and lym p ho c ytes (14,17). Small in f lam m a t ory nod u les of neu -tro p hils and macro p hages are en with hy p er a cute dis e a (8,33). Iso l ated evi d ence of myo c yte ne c ro s is is some t imes en. En d o c ar d ial and in t er s ti t ial fi b ro s is may be promi n ent (8,20). Spi r o c hetes char a c t er i s t ic of B burg d or f eri can be found near and in the in f il t rates, be t ween mu
s c le fi b res and in the en d o c ar d ium (8,14,17,34). In f lam m a t ory changes sug g es t ive of a form of vas c u l i t is may in v olve scat t ered small and large in -tra m yo c ar d ial ves s els (8,33). The find i ngs in Lyme car d i t is dif -fer from the his t o l ogi c al changes en in other car d i t i d es (8,17,34).
It ap p ears that the pres e nce of spi r o c hetes in the myo c ar -dium is in t rin s ic to the pa t ho p hysi o l o gy of Lyme car d i t is. It is not clear, how e ver, whether con t in u ed dis e a ac t iv i ty re -quires the pres e nce of live spi r o c hetes or whether it re s ults pri -mar i ly from immune- m ediated mecha n isms.The dis c rep a ncy en at histo p a t hol o gy be t ween the small number of spi r o -chetes re c ov e red and the ex t ent of the lym p hoplas m a c ytic in -fil t rate sug g ests a com b ined ef f ect of lo c al spi r o c hetal in f ec t ion with an im m u n o l ogi c al re a c t ion to the in f ec t ion (8,17,34).
CARDIOMYOPATHY
Late car d iac mani f es t a t ions re m ain to be fully de f ined. There is in c reas i ng evi d ence to sug g est that Lyme dis e a may be a cau of chronic con g es t ive car d io m yo p a t hy (8,15,35,36). An etio l ogi c al role of B burg d or f eri in long- s tanding chronic heart fail u re was firs
t sug g ested by the cul t i v a t ion of a strain of B burg d or f eri that was iso l ated from an en d o m yo c ar d ial bi o psy of a pa t ient with long- s tanding di l ated car d io m yo p a t hy (35). Fur t her m ore, a study by Sta n ek et al (35) found that the preva -lence of r um an t i b od i es to B burg d or f eri in pa t ients with di -lated car d io m yo p a t hy was higher than in con t rol groups. Also, in v es t i g a t ors at the Uni v er s ity of Min n e s ota found that 13% of pa t ients on their heart trans p lant list were r o p osi t ive for Lyme dis e a. In ad d i t ion, it is in t er e st i ng to note that some pa t ients with con g es t ive car d io m yo p a t hy have im p roved af t er in t ra v e n ous an t i b i o tic ther a py al t hough it is not cer t ain whether an t i b i o t i cs will be ef f ec t ive in stop p ing or re v ers i ng this dis e a pro c ess (7,38). Fur t her study is nec e s s ary be f ore Lyme dis e a can be es t ab l ished as a cau of chronic car d io -myo p a t hy (7). None t he l ess, B burg d or f eri in f ec t ion should be con s id e red in the dif f er e n t ial di a g n o s is and eti o l o gy of di l ated car d io m yo p a t hy (37).
The di a g n o s is of Lyme car d i t is is usu a lly sug g ested by care -ful his t ory, with par t icu l ar at t en t ion to the ab s ence of prior heart dis e a, resi d ence in or travel through an en d emic area, pre v i o us tick bite or pe c u l iar ery t he m a t ous le s ions, or co e x i s -tence of ob j ec t ive or sub j ec t ive neu r o l ogi c al dys f unc t ion that might sug g est Lyme dis e a (7). Un l ess Lyme c
ar d i t is oc c urs very early in the cour of the dis e a, r ol o gy should be posi -tive, but a nega t ive test does not rule out the di a g n o s is. The dif f er e n t ial di a g n o s is of Lyme car d i t is in c ludes other in f ec -tious and non i n f ec t ious caus (14).校园演讲稿
Lyme car d i t is can be pre v ented by avoid i ng ex p o s ure to B burg d or f eri. There is no vac c ine against B burg d or f eri avail -able for u in hu m ans (1). No defi n ite con c lu s ion re g ard i ng the thera p eu t ic role of an t i b i o t i cs in Lyme car d i t is can be drawn, al t hough an t i b i o t i cs may pre v ent the de v el o p m ent of car d i t is if given early in the cour of Lyme dis e a (27).
CONCLUSIONS
Lyme dis e a is a tick- b orne ill n ess caud by the spi r o c hete B burg d or f eri. Car d iac com p li c a t ions of Lyme dis e a gen e r a lly oc c ur in the early dis s emi n ated pha of the ill n ess and con s ist of atriov e n t ricu l ar block, my o peri c ar d i t is,in t ra v en t ricu l ar con d uc t ion dis t ur b ances, bun d le branch block and con g es t ive heart fail u re. De s pite the po t en t ial for he m o d y n amic in s ta b il -ity, the over a ll prog n o s is of Lyme car d i t is is very good, al -though re c ov e ry may be de l ayed and late mani f es t a t ions (di l ated car d io m yo p a t hy) may oc c ur.
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