IACC vat . IY. t v I
lam,- M2 12-1
32
Editorial Comment
Syndrome X :
The Ei:icardiai View*
KENNETH M, KESSLER, Ml) . F .ACC
Miami,
Florida
Syndrome X . Anginal pain can he a frightening and
disabling s ymptom . in the presence of normal coronary
angiographic findings (syndrome X) . anginat pain becomes a
frustrating paradox . a condition In which risk is statistically
low but reassurance may be inadequate . In patients with
syndrome X, several iovestigalors (1-3) have suggested that
the coronary artery abnormality is at the microvaseutar
level. Response to dpyndo mo le suggests that there are small
areas of ischemta that are sufficient to cause pain (presumed
to be mediated by adcnosioel but so patchy that. even when
the ischemic period is prolonged . they do not consistently
result in ischcmic wall motion abnormalities . Although the
syndrome traditionally has a benign prognosis, it is uncertain
whether there is a subset of patients Characterized by
conduction abnormality and eventual cardiomyopathy (4).
Focus on the microvascuiature has been further supported
by failure to consistently show abnormalities of vasomotion
of epicardial coronary arteries (5,61 and the physiologic
concept that the conduit epicardial vessels normally do not
exhibit resistance or limitation to flow .
Flow as a function of epicardial coronary artery diameter.
As the coronary vascular tree branches. the total crosssectional area increases and resistance : •3 flow may decrease .
Physiologically, this downstream decrease in resistance is
offset by preorteriolar resistance vessels and precapillary
sphincters that regulate flow largely in accordance with
autoregulatory mechanisms . We (7) recently proposed a
theoretical model of now through a 4-cm nonbranching
segment of the left anterior descending artery with a 2-mm
radius . Maximal flow through the segment was calculated at
150 mlfmin . a rate consistent with maximal ranges of physiologic flow. Assuming a basal flow of 70 mllmin . a normal
flow reserve of 5 times baseline is defined . A 25% decrease
in arterial radius would decrease coronary flow reserve from
5 to 1 .6 .f68%1
Although mtmerous assumptions have been
made in this analysis . epicardial coronary diameter may play
a role in limiting total flow during maximal vasodilatian .
-[,-,h p„r.a.hra i . y„n .nvt e~f u,r nfl,,.:r.r . ( ,l rvMlat„gy
"f"l ao sieves of the authors and Jo naa nccecsailti represent eke viev .s of
IACC or the •tnten(an College at Cvrdioluwy,
Pram the Dtvhbo of CarJiol,rpy. Dcpaamcnl ar Medicine . t :oaenaan nl
stenri School of hledinne and the Cxrdivkvyc Section . Medico! Screws,
Veto- Ando t.tuhaat Center . htiarti . Hand ..
Aitlew far rcr",im= : gcnamh M. kerder. M D . Ywtes .wr ar Medicine.
Cheer. Cnrdielot) Senior
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,? 1551
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leSemen .MLna,FtaridaMMitt,
by the American Catape
of
Cardialapy
Therefore, r-asudilator reserve ,way be limited in vascular
beds that an: supplied by an cpicardial coronary artery that
is disproportionately small in size because of 1) anatomic
variation, 21 diffuse narrowing by fibrosis ar atherosclerosis .
or 3) ahaemal ,ueomation . These conditions represent
dij) iose, fixed and functional coronary artery abnormalities .,
opposed to the ffmral, fixed (atheroscleroticl and functional
(spasm) abnormalities that we more often consider.
Eplcardiul vasomotor dysfunction . Tire present srndy .
The Current study by Vnnts et al . 18) io this issue of the
Journal addresses abnormalities in epicardial vasomotion as
tested by responses to acetylcholine . In contrast to the
uniform vasoconstrictor response ha ergonovine, the normal
vascular response m acetylcholine is concentration dependent . that is . vasedtlahoa at lower concentrations and vasoconstriction at higher concentrations . Vrints et ai . I81 found
paradoxie vasoconstriction at low concentrations of acetyl-
choliae in patients with typical angina and normal cpicardial
coronary arteries . This paradoxie vasoconstriction was not
noted in patients who had atypical chest pain . The findings
broaden the concepl of syndrome X by including the potential of epicardial coronary artery vascular dysfunction and
consequent flow limitation in the pathogenesis of this syndrome . These findings also provide a basis to consider
routine acetyk :holine testing in patients who have angina or
even atypical symptoms and normal epicardial coronary
arteries. Such testing appears to be feasible and safe atthough further evaluation is certainly needed . Limitations of
the current study (8) include the failure to evaluate responses
to ergonovine and the failure to exclude microvascular
abnormalities. The lack of an integrated multilevel approach
to this subject is common. Furthermore, in a larger study
group, one would expect that some patients with typical
angina would not show paradoxie vasoconstriction whereas
some patients with atypical chest pain would . suggesting that
acetylcholine testing may be applicable to a variety of chest
pain syndromes .
Future direction : focus on patient care . fhe patient is too
frequently lost in our "high tech" arguments regarding the
pathogenesis of this disorder and in our defensiveness when
we find anatomically normal coronary arteries . When we
give patients the good news that they have normal coronary
arteries and an excellent prognosis, we often disregard the
fact that they may remain disabled and even acquire an
unwarranted neurotic label . A systematic approach to the
evaluation of epicardial and microvascular dysfunction and
admission of our ignorance of the pathogenesis of many
chest pain syndromes would serve patients better . Treatment with nitrates, calcium channel hlneking agents, betaadrenergic blocking agents and aminopliylline needs further
evaluation (9-11). Gastrointestinal abnormalities should be
sought when appropriate but positive findings do not exclude
coronary vasomotion abnormalities, because the two may
coexist (12) . It is also known that fixed atherosclerouc
stenosis and vascular dysfunction coexist t By future sttuties
07341aYs'ob35n
J .ACC Vat . I9. Na . I
lanuery IY77 :53-a
KESSLE.R
EDITORIAL COMh1EMT
need to evaluate whether vascular dysfunction may help to
explain residual chest pain in patients who have undergone
coronary revascularizaiinn and have little or re, nhieclive
evidence of ischemia.
Whether epicardial sascular dysfunction is truly a prca.l9eroselelolic or Curly alhcronulerotiu legion that would
benefit from primary prevention and aspirin therapy is
uncertain . 'the preponderance of women with syndrome X
suggests that vascular dysfunction is not solely an athera
scterosis.retated disorder . Perhaps we should consider a
dual classification : Il alheruschxusis-associated vascular
dysfunction, and 21 generalized vascular dysfunclon tin'
eluding abnormalities offorearm . airway and gastraimsstieal
,mooch muscle). The common link would he an endothelial
metabolic abnormality 1141 leading to inlpai: ed smooth nius .
etc relaxation and . consenuently . enhanced comarictiun .
Future studies should explore and unity the pothophysinlogv
of fixed and functional . focal and dltluse coronary arlery
abnermalities . and lead to a svstemalizcd approach to the
clinical Icsting and treatment of patients with a chest pain
syndrome .
1 . %-- BE Tie.0~;rBoer,denrnnary ,r,r~r,• ;nlliow .dhrendi,easr
J I . CAI Cerdivl 19911:15 775-83.
4 . Ilpntrk 0 . Schuler G . Weuerauer K. Munthey 1 . Scheare F . Kattn W .
rnnr- y ear
andy ;n Poll- , .d, ;,opine prew6i, end n oat
5 .005555 aneriug,m .I syndrome X • •I . Circulation 1989;91);1610 -6 .
Nail JC Ibn„uslin ll .Galsni AR . eI aI. Epla,Nlal coronary artery lone
ana rtam'aC• rn purieni :: wirh normal Cmanury uneriogrums end reduced
~~ ~, n n,, ~pu,vc 1+yndrume %i . 1 Am C II C :+rdio1 1991 ;18 :50-4 .
n Morton.05.1a-uuOM .EhediFR .etal.Abnormals .r.naryva+om .linn
dorms e
n pvlmnl, wnh --l --k enene, and reduced
, Aou raw-t
. Cirwlanw 14X9-,,79 i16 77 .
r nsuelfeml-l .KegseiVMCamparisunofpmtinulleftanterlnrdescendIng ::nutesnmlkaroroneryarterydincr . nsmavdcvalvexenne,eand
kynmropma c . rdmmyinu! ii liellerl. Am 1 Cardiul I'})P67.3?55
x Cnrl, Cl51 full lie Hitter E. Herman At, Snccek 1P . Impared
e m :IXk el i um-dapendenl choli nerpc coronary vanedilal'am in puGenn wirh
.npln' eoJ normal mronery enennieniins . 1 Am Con C,d ;n1 1993:14. LI
9 . W,rn,S'w .RdtanlA .heron .NahelCO.ScornML.pd1R.r.v,dencear
v tsiicrket S rnormli.n In anpmpraphlxally --l . ... no, initial of
Irauml, wren cmenory anery di,eae . Cimulelion l"'J .7'1o?a1-91.
10 . Cannon RU. Wanmn HSI . Kos19B [7R• Epriria SE Efioey of cola sun
. nnel h'ockea Therapy in pelima wnh enpna pcc,one due t ., .mall
mars hers diocese wrill abnormal vacadilatar reserve . Am J Cordial
13- Ifupi.rrJ,nl R . 9ogh1 A. &alert ; L. I'uetdu P, Comperinon o1 velapamll
cre ., .
a
:,heropy nrsymdr .uu w . air, 7 Cardrm I9s9 :M1iilRn.All.
11 EmdmM .VsagoE .LaltaniiF.L'AtdraleA .tmpruvedexcrciseuupaciiy
o iS .clue ammophyllhc edminoaafon :n patients will syndrome X .
I Am Cnll ('onhoi 1919'.49:1459-1.
11 ..,norm line Callow LL. Vashe PN . eI al . Coranery flow ro
e,aphageol motility and chess pain in pahmis Win eegiographically
normal carnoerr sT16, Am 1 Med 1990:99 :21 7-2211 . nn„enkc h . Rus,c H. Endalhdial medulminn of cnrotary lane. Pros
C ardw+a,c 1l11 1554.11 t49-80
a
References
I . Painwnk
Canon RO l11 . E,- .o SE .' .tier wuiur enpmofche,
anglnpraphtsct1 -A corn
•r lerie+ .Ann I Czrdml
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'_. Maser, A. Crew F . K1,ai IC . Crake T. Mccham,m, a , In
o,ad .. e X .1 Am Coll Cendial 1991 .17A99-1 06
33