Table Of ContentANGINA PECTORIS WITH NORMAL
CORONARY ARTERIES: SYNDROME X
DEVELOPMENTS IN CARDIOVASCULAR MEDICINE
121. S. Sideman,R. Beyarand A. G. Kleber(eds.): CardiacElectrophysiology,Circulation,
andTransport. Proceedingsofthe7thHenryGoldbergWorkshop(Berne, Switzerland,
1990). 1991.1SBNO-7923-1145-0.
122. D. M. Bers: Excitation-Contraction Coupling and Cardiac Contractile Force. 1991.
ISBN0-7923-1186-8.
123. A.-M. SalmasiandA. N. Nicolaides(eds.): OccultAtheroscleroticDisease. Diagnosis,
Assessmentand Management. 1991. ISBN0-7923-1188-4.
124. J. A. E. Spaan: Coronary Blood Flow. Mechanics, Distribution, and Control. 1991.
ISBN0-7923-1210-4.
125. R. W. Stout(ed.): Diabetesand Atherosclerosis. 1991. ISBN0-7923-1310-0.
126. A. G.Herman(ed.): Antithrombotics. PathophysiologicalRationaleforPharmacological
Interventions. 1991. ISBN0-7923-1413-1.
127. N. H. J. Pijls: Maximal Myocardial Perfusion as a Measure of the Functional
Significance ofCoronary Arteriogram. From a Pathoanatomic to a Pathophysiologic
InterpretationoftheCoronaryArteriogram. 1991. ISBN0-7923-1430-1.
128. J.H.C. ReiberandE. E. v. d. Wall(eds.): CardiovascularNuclearMedicineandMRI.
Quantitationand Clinical Applications. 1992. ISBN0-7923-1467-0.
129. E. Andries, P. Brugadaand R. Stroobrandt(eds.): Howto Face "theFaces"ofCardiac
Pacing. 1992. ISBN0-7923-1528-6.
130. M. Nagano,S. MochizukiandN. S. Dhalla(eds.): CardiovascularDiseaseinDiabetes.
1992. ISBN0-7923-1554-5.
131. P. W. Serruys, B. H. Strauss and S. B. King III (eds.): Restenosis after Intervention
with New MechanicalDevices. 1992. ISBN0-7923-1555-3.
132. P. J. Winter (ed.): Quality ofLife after Open Heart Surgery. 1992. ISBN 0-7923
1580-4.
133. E. E. vanderWall, H. Sochot, A. Righetti and M. G. Niemeyer(eds.): What is new
inCardiacImaging? SPECT, PETand MRI. 1992. ISBN0-7923-1615-0.
134. P. Hanrath, R. Uebis and W. Krebs (eds.); Cardiovascular Imaging by Ultrasound.
1992. ISBN0-7923-1755-6.
135. F. H. Messerli (ed.): CardiovascularDiseasein the Elderly, 3rd ed. 1992. ISBN
0-7923-1859-5.
136. J. Hess and G. R. Sutherland (eds.); Congenital Heart Disease in Adolescents and
Adults. 1992. ISBN0-7923-1862-5.
137. J. H. C. Reiber and P. W. Serruys (eds.): Advances in Quantitative Coronary
Arteriography. 1992. ISBN0-7923-1863-3.
138. A.-M. SalmasiandA. S. Iskandrian(eds.): CardiacOutputandRegionalFlowinHealth
and Disease. 1993. ISBN0-7923-1911-7.
139. J. H. Kingma, N. M. van Hemel and K.~. Lie (eds.).: Atrial Fibrillation, aTreatable
Disease? 1992. ISBN0-7923-2008-5.
140. B. Ostadal, N. S. Dhalla(eds.): HeartFunctionin Health and Disease. 1993. ISBN
0-7923-2052-2.
141. D. Noble and Y.E. Earm (eds.): Ionic Channels and Effect ofTaurine on the Heart.
ProceedingsofanInternationalSymposium(Seoul, Korea, 1992). 1993. ISBN0-7923
2199-5.
142. H.M. Piper and CJ. Preusse (eds.): Ischemia-repeifusion in Cardiac Surgery. 1993.
ISBN0-7923-2241-X.
143. J. Roelandt, EJ. Gussenhovenand N. Born (eds.): Intravascular Ultrasound. 1993.
ISBN0-7923-2301-7.
144. M.E. Safar and M,F. O'Rourke (eds.): The Arterial System in Hypertension. 1993.
ISBN0-7923-2343-2.
145. P. W. Serruys, D.P. Foley and PJ. de Feyter (eds.): Quantitative Coronary
Angiographyin ClinicalPractice. 1993. ISBN0-7923-2368-8.
146. J. Candell-Riera and D. Ortega-Alcalde (eds.): Nuclear Cardiology in Everyday
Practice. 1993. ISBN0-7923-2374-2.
147. P. Cummins(ed.): GrowthFactorsandtheCardiovascularSystem. 1993. ISBN7923
2401-3.
148. K. Przyklenk, R.A. Klonerand D.M. Yellon (eds.): Ischemic Preconditioning: The
ConceptofEndogenousCardioprotection. 1993. ISBN0-7923-2410-2.
ANGINA PECTORIS WITH NORMAL
CORONARY ARTERIES: SYNDROME X
Edited by
JUAN CARLOS KASKI
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Library of Congress Cataloging-in-Publication Data
Angina peetoris with normal eoronary arteries (syndrome x) / edited by Juan
Carlos Kaski.
p. em. -- (Developments in eardiovaseular medieine: v. 152)
ISBN 978-1-4613-6111-4 ISBN 978-1-4615-2596-7 (eBook)
DOI 10.1007/978-1-4615-2596-7
1. Angina peetoris. 2. Coronary arteries--Physiology. 1. Kaski,
Juan Carlos. II. Series.
[DNLM: 1. Fragile X Syndrome. 2. Angina Peetoris. Wl DE997VME
v.152 1994/ WG 298 A5885 1994]
RC685.A6A55 1994
616.1 '22--de20
DNLM/DLC
for Library of Congress 93-43083
CIP
Copyright © 1994 Springer Science+Business Media New York
Originally published by Kluwer Academic Publishers in 1994
Softcover reprint of the hardcover 1s t edition 1994
AlI rights reserved. No part of this publieation may be reprodueed, stored in
a retrieval system or transmitted in any form or by any means, meehanical,
photo-eopying, reeording, or otherwise, without the prior written permis sion of
the publisher, Springer Science+Business Media, LLC.
Printed an acid-free pap er.
Table of Contents
Contributing Authors vii
Preface ix
Acknowledgements xi
Chest Pain With Normal Coronary Arteriograms:
Clinical Features And Prognosis
1. Syndrome X: A heterogeneous syndrome. Historical background,
clinicalpresentation,electrocardiographicfeatures, andrationalpatient
management. Anoverview. J.C. Kaski 1
2. Prognosis and therapy in patients with angina and normal coronary
arteriograms. H. G. Kemp, Jr. 19
3. Chest pain with normal coronary arteriograms: Oesophageal
abnormalities-Thegastroenterologist'sview. J. S. de Caestecker 31
4. Chest pain with normal coronary arteries: Psychological aspects.
S.G. Potts andC. Bass 65
5. Chestpain andangiographically normalcoronaryarteries in patients
with systemic hypertension and left ventricular hypertrophy.
Mechanisms. W. MotzandB.E. Strauer 89
6. Syndrome X: A non-ischaemic syndrome? "False positive" ST
segment shifts, ischaemia, myocardial perfusion abnormalities and
increasedsensitivitytopainin syndromeX. P. Poole-Wilson 111
7. SyndromeX -An early form ofcardiomyopathy? W. KUblerandG.
Schuler 125
Syndrome X And Microvascular Angina • Abnormal
Coronary Blood Flow Reserve
8. Microvascularangina. R.O. Cannon1II 137
9. Studiesofcoronarybloodflowandmyocardialmetabolismin patients
with chestpain and angiographically normalcoronary arteries. P.G.
Camici 149
vi
10. Criticalviewoftheconceptofcoronaryflowreserve. Advantagesand
disadvantages of the current methods used for the assessment of
coronaryflow reserve in theclinical setting. A. L'Abbate 165
11. The coronary microcirculation in patients with normal coronary
arteries and symptoms ofchest pain - Myocardial blood flow rate,
capillary permeability and interstitial diffusion. S. Hauns¢ andJ. H.
Svendsen 175
Angina With Normal Coronary Arteriograms
Pathogenetic Hypotheses
12. Pre-arteriolar coronary constriction in pathogenesis ofsyndrome X.
e.
Roleofadenosine. G. Lanza, G. M. Rosano andA. Maseri 193
13. Abnormal neurohumoral control in pathogenesis of syndrome X.
C.M.e. Rosano andJ.e. Kaski 211
14. Epicardial coronary artery responses in patients with angina and
normal coronary arteriograms. R. Bugiardini, A. Borghi and A.
Pozzati 225
15. Endothelial dysfunction in patients with anginaandnormal coronary
arteriograms. P. Collins 237
16. Roleofoestrogendeficiencyin women withsyndromeX. P. Sarrel 249
17. Summary,conclusionsandfutureperspectives. A. H. Henderson 267
Index. ~3
LIST OF CONTRIBUTORS
Christopher Bass, John Radcliffe Hospital, Oxford, UK
Alberico Borghi, Istituto di Patologia Medica III, Bologna, Italy
Raffaele Bugiardini, Istituto di Patologia Medica, Bologna, Italy
John de Caestacker, St. George's Hospital, London, UK
Paolo G. Camici, Hammersmith Hospital, London, UK
Richard O. Cannon, NIH, Bethesda, MD USA
Peter Collins, National Heart Lung Institute, London, UK
Stig Haunso, Copenhagen University Hospital, Denmark
Andrew H. Henderson, Univ. of Wales College of Medicine, UK
JaunCarlos Kaski, St. Georges HospitalMed. School, London,UK
Harvey Kemp, Jr., New York, New York, USA
Wolfgang Kubler, Klinikum der Universitat Heidelberg, Germany
Antonio L'Abbate, Istituto di Fisiologia Clinica, Pisa, Italy
Gaetano A. Lanza, Istituto di Cardiologia, Roma, Italy
Attilio Maseri, Universita Cattolica del Sacro Cuore, Roma, Italy
Wolfgang Motz, Medizinische Klinik und Polikinik B, Germany
Philip A. Poole-Wilson, National Heart Lung Institute, UK
Stephen G. Potts, University of Edinburgh, UK
Andrea Pozzati, Istituto di Patologia Medica III, Bologna, Italy
Giuseppe Rosano, National Heart Lung Institute, UK
Philip Sarrel, Yale University Health Services, CT., USA
Gerhard Schuler, Klinikum der Universitat Heidelberg, Germany
B. E. Strauer, Klinik Poliklinik B der U. Dusseldorf, Germany
Jesper Hastrup Svendsen, Copenhagen Univ. Hospital, Denmark
Preface
"Anginapectoriswithnonnal coronary arteriograms" isa common entity which has
puzzledcardiologistsalmostsincetheadventofcoronaryarteriography. Asa matter
of fact, chest pain in the absence ofatheromatous coronary disease represented a
diagnosticproblemevenbeforethearteriographyera. "Pseudo-angina" (chestpainin
theabsenceofcoronaryarteriosclerosis) wasdescribedbyWilliamOslerinhisbook
"ThePrinciplesandPracticeofMedicine",as the"chiefdifficulty" in thediagnosisof
"trueangina". Pseudo-anginawasa"commonaffectionin women" butcouldalsobe
foundin"neurasthenicmen".
Despitemajoradvances in the understandingofthepathophysiologyofanginain
recent years and a multitude of studies on the subject, the cause and mechanisms
underlying the syndromeofangina with nonnalcoronary arteries remain unknown.
Indeed, results of investigations are controversial and speculation still prevails
regarding thenatureofthesocalled"SyndromeX".
Why therefore write a book about "Syndrome X"; an ill-defined entity which
offerssomanyobscureaspects; asyndromewhosedefinition is far from precise? It
is because of its controversial nature, the lack of agreement between researchers
regarding the precise definition of the syndrome, and the sense of frustration that
"Syndrome X" imposes on both patient and physician, that I thought that a
monograph on the subjectwas necessary. Iwas hauntedby the ideaofproducing a
book which would reflect not only current, objective, cardiological knowledge on
syndrome X, but also the views of specialists in other medical fields who also
"battle" with theproblemofchestpainofunexplainedorigin. Irealized thattheidea
of a multidisciplinary monograph on "Syndrome X" was not only desirable, but
possible, after our "Workshop on Angina with Normal Coronary Arteries" in June
1992at St. George's Hospital inLondon. At this meeting, which gathered together
many of the contributing authors of this book, we had fruitful discussions on the
heterogeneityandpossiblenatureofSyndromeX. Theneedtoworkincollaboration
towardsabetterunderstandingoftheproblembecameobvious. Itwas then apparent
to me that there was "light at the end of the tunnel" insofar as investigators and
x
clinicians witha genuine interestin syndrome X made an effortto carefully dissect
thediversecomponentsofthisentity.
Thecontributing authors haveacceptedthechallengeand "teamed up" undermy
editorship,forwhich Iamextremelygratefulandunderstandablyproud. Weaimedat
providingacomprehensive viewofthe problem ofSyndromeX. The authors, who
are notonly top scientistsbutalso sagaciousclinicians, havegenerouslycontributed
their knowledgeand personal views to this monograph. I trust that the readers will
enjoy,asmuchIdid, going through every pageofthebookto discoverthemultitude
ofestablishedconceptsandnew ideassocarefully"seeded"byauthoritiesinthefield.
Almostevery importantaspectofsyndromeX hasbeen tackledin the bookand the
reader will be exposed not only to the cardiologists' opinion, but also to the
authoritative views of the gastroenterologists, gynaecologists and psychiatrists,
extremely well represented in this monograph. Our book deals with the
"cardiologistssyndromeX" andnot the metabolicentity recently termed "syndrome
X". Thepossibleconnection between the two "syndromeX", however, isdiscussed
in the book.
This bookdoes notattempt to be "the last word" on SyndromeX, an impossible
taskwhendealingwithsucharapidlyevolvingfield. Weareaware thatperhapsonly
some ofthe new challenging concepts and hypotheses discussed in the monograph
may be confirmed in the future (but at present we do not know which!) whereas
others will have tobeabandoned when supersededby new concepts. Ouraim is to
contribute to the understanding of Syndrome X and we will feel rewarded if this
monograph serves the double purpose of helping clinicians to manage their
SyndromeXpatientsbetterandinvestigatorstoopennewavenuesforresearch.
JuanCarlosKaski
London
Acknowledgments
I am greatly indebted to the authors, who generously contributed authoritative
chapters to the monograph; and to Allison Baker, my Research Assistant, who
workedextremelyhardindiverseaspectsoftheeditorialprocess. Hercontributionto
thebookwastruly vitalandIamverygratefulforherhelpandencouragement.
Aneducationalgrantfrom BayerUKmadethisbookpossible. Iacknowledgethe
kindnessandgenerosityofDrGarryMacdonaldandRobinBhattacheIjeewhodecided
to support our monograph taking into account its scientific value rather than its
negligible"marketing" potential.
Ithankmy wife, Marta,andmychildrenJuan Pablo,DiegoandMarlaCeciliafor
their loveand patienceandalso for encouragingme to geton with this work. Iam
also grateful to my father, M. Kaski, MD, who taught me that Medicine is about
caringandinsistedthatpatientsshouldbelistenedto.
