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DynamicElectrocardiographyEDITED BY
Professor Marek Malik MSc, PhD,MD, DSc, DSc (Med), FACC, FESCProfessor of Cardiac Electrophysiology,Department of Cardiac and Vascular Sciences,St. George’s Hospital Medical School,London SW17 0RE, United Kingdom
AND
Professor A. John Camm QHP, BSc,
MD, FRCP, FESC, FACC, FAHA, FCGC, CStJProfessor of Clinical Cardiology,Department of Cardiac and Vascular Sciences,St George’s Hospital Medical School,London SW17 0RE, United Kingdom
DynamicElectrocardiographyEDITED BY
Professor Marek Malik MSc, PhD,MD, DSc, DSc (Med), FACC, FESCProfessor of Cardiac Electrophysiology,Department of Cardiac and Vascular Sciences,St. George’s Hospital Medical School,London SW17 0RE, United Kingdom
AND
Professor A. John Camm QHP, BSc,
MD, FRCP, FESC, FACC, FAHA, FCGC, CStJProfessor of Clinical Cardiology,Department of Cardiac and Vascular Sciences,St George’s Hospital Medical School,London SW17 0RE, United Kingdom
© 2004 by Futura, an imprint of Blackwell Publishing
Published by Futura, an imprint of Blackwell PublishingBlackwell Publishing, Inc./Futura Division, 3 West Main Street, Elmsford, New York 10523,USABlackwell Publishing, Inc., 350 Main Street, Malden, Massachusetts 02148-5020, USABlackwell Publishing Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UKBlackwell Science Asia Pty Ltd, 550 Swanston Street, Carlton, Victoria 3053, Australia
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04 05 06 07 5 4 3 2 1
ISBN: 0-4051-1960-8
Library of Congress Cataloging-in-Publication Data
Dynamic electrocardiography / [edited by] Marek Malik, A. John Camm. – 1st ed.p. ; cm.
Includes bibliographical references and index.ISBN 1-405-11960-8
1. Electrocardiography.[DNLM: 1. Electrocardiography. WG 140 D9974 2004] I. Malik, Marek. II. Camm,
A. John.RC683.5.E5D966 2004616.1¢207547 – dc22
2003023262
A catalogue record for this title is available from the British Library
Acquisitions: Steve KornProduction: Fiona Pattison and Deirdre PrinsenTypesetter: SNP Best-set Typesetter Ltd., Hong KongPrinted and bound by CPI Bath, Bath, UK
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To Kate and Joy
Contents
Contributors, vi
Foreword, xvi
Preface, xviii
Section I Heart rate variability, 1
1 Physiological background of heart ratevariability, 3Roger Hainsworth
2 Standard measurement of heart ratevariability, 13Marek Malik
3 Nonlinear dynamics of RR intervals, 22Timo H. Mäkikallio, Juha S. Perkiömäki and Heikki V. Huikuri
4 Correlations among heart rate variabilitycomponents and autonomic mechanisms, 31Dwain L. Eckberg
5 Physiological understanding of HRVcomponents, 40Federico Lombardi
6 Autonomic balance, 48Alberto Malliani and Nicola Montano
7 Heart rate variability: stress and psychiatricconditions, 57Gary G. Berntson and John T. Cacioppo
8 Circadian rhythm of heart rate and heartrate variability, 65Phyllis K. Stein
9 Time–frequency analysis of heart ratevariability under autonomic provocations, 73Solange Akselrod
10 Effects of drugs, 83Xavier Copie and Jean-Yves Le Heuzey
11 Heart rate variability in healthypopulations: correlates and consequences, 90Annie Britton and Harry Hemingway
12 Heart rate variability in ischaemic disease, 112Robert E. Kleiger and Phyllis K. Stein
13 Heart rate variability in heart failure, 122Roger Moore and James Nolan
14 Heart rate variability in diabetes andneuropathies, 133Ernest L. Fallen
Section II Baroreflex, 141
15 Physiological background ofbaroreflex, 143Barbara Casadei
16 Invasive determination of baroreflexsensitivity, 154Maria Teresa La Rovere
17 Noninvasive provocations of baroreflexsensitivity, 162Josef Kautzner
18 Analysis of the interactions between heart rate and blood pressure variabilities, 170Sergio Cerutti, Giuseppe Baselli, Anna M.Bianchi, Luca T. Mainardi and Alberto Porta
19 Arterial baroreflexes in ischaemic heart disease, and their role in sudden cardiac death, 180Dwain L. Eckberg
20 Heart rate turbulence on Holter, 190Raphael Schneider, Petra Barthel and Mari Watanabe
21 Heart rate turbulence in pacing studies, 194Dan Wichterle and Marek Malik
22 Physiological hypotheses on heart rateturbulence, 203Andreas Voss, Vico Baier, Alexander Schirdewan and Uwe Leder
iii
23 Heart rate turbulence in ischaemic heartdisease, 211Axel Bauer and Georg Schmidt
Section III Ischaemic patterns, 215
24 Electrocardiographic background, 217Marian Vandyck-Acquah and Paul Schweitzer
25 Dynamics of silent ischaemia, 233Shlomo Stern
26 Dynamics of ST segment in ischaemic heartdisease, 238Divaka Perera, Sundip J. Patel and Simon R. Redwood
27 Spatial patterns of ST segment shift duringmyocardial ischaemia, 250B. Milan Horácek and Galen S. Wagner
28 ST segment trend monitoring of acutechest pain patients, 260J. Lee Garvey
29 Circadian patterns of ischaemic episodes, 269Shlomo Feldman
30 Electrocardiographic findings in patientswith cardiovascular syndrome X, 277Juan Carlos Kaski and Juan Cosin-Sales
Section IV Ventricular repolarization, 289
31 Cellular basis for the repolarization waves ofthe ECG, 291Charles Antzelevitch
32 Individual QT/RR relationships, 301Velislav Batchvarov and Marek Malik
33 Circadian patterns of QTc interval, 315Peter Smetana, Esther Pueyo, Katerina Hnatkova, Marek Malik
34 QT dispersion, 326Velislav Batchvarov and Marek Malik
35 Morphological assessment of T wave patterns, 350Markus Zabel and Marek Malik
36 Circadian pattern of T wave morphology, 358Velislav Batchvarov
iv Contents
37 QT interval dynamics during exercise, 371Paul Kligfield and Peter M. Okin
38 T wave and QT interval changes related tomyocardial ischaemia, 380Juha Hartikainen
39 Influence of rhythm abnormalities onventricular repolarization, 390Rory Childers
40 Dynamics of acquired long QT syndrome, 406Elijah R. Behr and A. John Camm
41 Electrocardiogram of Brugada syndromeand its dynamic patterns, 417Maximo Rivero-Ayerza, Ramon Brugada, Josep Brugada, Peter Geelen and Pedro Brugada
42 Electrocardiographic T wave changes in leftventricular hypertrophy, 425Michael R. Franz
43 Macro T wave alternans, 433Robert L. Lux and Konrad Brockmeier
44 Microscopic T wave alternans, 439Otto Costantini
45 T wave alternans in ischaemic heart disease, 448Stefan H. Hohnloser
46 Dynamic repolarization changes andarrhythmia risk assessment innonischaemic heart disease, 454Richard L. Verrier and Aneesh Tolat
Section V Atrial fibrillation, 463
47 Pathophysiology of the atrial fibrillationelectrogram, 465Ulrich Schotten and Maurits A. Allessie
48 P wave abnormalities before AF episodes, 475Polychronis E. Dilaveris
49 Dynamics of atrial electrogram in AF, 486Bertil S. Olsson, Carl J. Meurling, Leif Sörnmoand Martin Stridh
50 Detection of paroxysmal atrial fibrillationepisodes, 493Rahul Mehra and David Ritscher
Contents v
51 Circadian pattern of AF paroxysms, 500Antonio Michelucci, Paolo Pieragnoli, Andrea Colella, Gianfranco Gensini and Luigi Padeletti
52 Monitoring after cardioversion of atrialfibrillation, 506Samuel Lévy
53 Heart rate profile in chronic atrialfibrillation, 511Alessandro Capucci, Giovanni Quinto Villani and Massimo Piepoli
54 Monitoring of heart rate control in atrialfibrillation, 517Shamil Yusuf and A. John Camm
55 Autonomic influence of atrial fibrillation, 530Philippe Coumel
56 Long time monitoring of cardiac rhythm inpatients with atrial fibrillation, 537Milos Kesek and Mårten Rosenqvist
Section VI Ventricular arrhythmias, 547
57 Monitoring ectopic activity, 549Bogdan G. Ionescu, Xavier Vinolas, IwonaCygankiewicz, Antoni Bayés Genis and Antoni Bayés de Luna
58 Circadian pattern of arrhythmic episodes, 560Yi-Fang Guo and Phyllis K. Stein
59 Holter monitor-guided antiarrhythmictherapy, 565Kelley P. Anderson
60 Dynamics of heart rate before arrhythmias, 571Polychronis E. Dilaveris and John E. Gialafos
Section VII Electrocardiogram of animplanted device, 581
61 Electrocardiographic monitoring withimplantable devices, 583Richard Houben and Fred Lindemans
62 Ischaemic patterns, 593Andreas Grom, Christoph Bode and Manfred Zehender
63 State-of-the-art marker channels, 599Walter H. Olson
64 Interpretation of device stored rhythms andelectrocardiograms, 608Paul J. Erlinger and Gust H. Bardy
Index, 627
Solange Akselrod, PhDProfessor Head of Medical PhysicsAbramson Center for Medical PhysicsSchool of Physics and AstronomyTel-Aviv UniversityRamat-Aviv, [email protected]
Maurits A. Allessie, MD, PhDProfessor of PhysiologyChairman of the Department of PhysiologyDepartment of PhysiologyUniversity MaastrichtPO Box 6166200 MD MaastrichtThe [email protected]
Kelley P. Anderson, MD, FACCCardiologistDepartment of Cardiology 2D2Marshfield Clinic1000 North Oak AvenueMarshfield, WI [email protected]
Charles Antzelevitch, PhD, FACC, FAHAExecutive Director/Director of ResearchGordon K Moe Scholar and Professor of PharmacologyMasonic Medical Research Laboratory2150 Bleecker StreetUtica, NY [email protected]
Vico Baier, DIngResearch AssistantDepartment of Medical EngineeringUniversity of Applied Sciences JenaCarl-Zeiss-Promenade 207745 [email protected]
Gust H. Bardy, MD, FACCClinical Professor of MedicineUniversity of WashingtonBox 356422: Suite 3007900 East Greenlake DriveSeattle, WA [email protected]
Petra Barthel, MDSenior ResidentDeutsches Herzzentrum MünchenTechnische Universität MünchenArbacherstrasse 1081371 [email protected]
Giuseppe Baselli, MSProfessor in Biomedical EngineeringDepartment of BioengineeringPolytechnic University in MilanoPiazza Leonardo da Vinci 3220133 [email protected]
Velislav N. Batchvarov, MDSenior Research FellowDepartment of Cardiac and Vascular SciencesSt. George’s Hospital Medical SchoolCranmer TerraceLondon SW17 0REUnited [email protected]
Axel Bauer, MDResidentDeutsches Herzzentrum MünchenTechnische Universität MünchenArbacherstrasse 1081371 [email protected]
Contributors
vi
Contributors vii
Antoni Bayés de Luna, MD, PhD, FESC, FACCProfessor of CardiologyChief of Institute of CardiologyHospital de Sant Pau i Santa CreuSt Antoni Ma Claret 16708025 [email protected]
Antoni Bayés Genis, MD, PhD, FESCAssistant ProfessorHeart Failure Unit CoordinatorInstitute of CardiologyHospital de Sant Pau i Santa CreuSt Antoni Ma Claret 16708025 [email protected]
Elijah Behr, MA, MBBS, MRCPSpecialist RegistrarDepartment of Cardiac and Vascular SciencesSt George’s Hospital Medical SchoolCranmer TerraceLondon SW17 0REUnited [email protected]
Gary G. Berntson, PhDProfessor of Psychology, Psychiatry & PediatricsDepartment of PsychologyThe Ohio State University1885 Neil AvenueColumbus, OH [email protected]
Anna M. Bianchi, MSAssistant ProfessorDepartment of BioengineeringPolytechnic University in MilanoPiazza Leonardo da Vinci 3220133 [email protected]
Christoph Bode, MD, FESCProfessor of Medicine and ChairmanUniversitätsklinikum FreiburgInnere Medizin III, Kardilogie und AngiologieHugstetterstrasse 55D-79106 [email protected]
Annie Britton, PhDLecturer in Epidemiology and Public HealthInternational Centre for Health and SocietyDepartment of Epidemiology and Public HealthUniversity College London1-19 Torrington PlaceLondon WC1E 6BTUnited [email protected]
Konrad Brockmeier, MDProfessor of PediatricsHead of Pediatric CardiologyUniversity of CologneJoseph-Stelzmann-Strasse 950924 Köln [email protected]
Josep Brugada, MD, PhDDirector, Arrhythmia UnitCardiovascular InstituteHospital ClinicUniversity of BarcelonaVillarrael 170, [email protected]
Pedro Brugada, MD, PhD, FESC, FAHAProfessor of MedicineDirector, Arrhythmia UnitOLV Hospital, Cardiovascular Center Aalst9300 [email protected]
Ramon Brugada, MDDirector, Molecular Genetics ProgramMasonic Medical Research Laboratory2150 Bleecker StreetUtica, NY [email protected]
A. John Camm, QHP, BSc, MD, FRCP, FESC, FACC,FAHA, FCGC, CStJBritish Heart Foundation Professor of Clinical CardiologyDepartment of Cardiac and Vascular SciencesSt. Georges Hospital Medical SchoolCranmer TerraceLondon SW17 0REUnited [email protected]
John T. Cacioppo, PhDTiffany and Margaret Blake Distinguished Service ProfessorDepartment of PsychologyThe University of Chicago5848 South University AvenueChicago, IL [email protected]
Alessandro Capucci, MD, FESC, FACCDirector of Department of CardiologyGuglielmo da Saliceto General HospitalCantone del Cristo29100 [email protected]
Barbara Casadei, MD, DPhil, FESC, FRCPReader in Cardiovascular MedicineUniversity Department of Cardiovascular MedicineJohn Radcliffe HospitalOxford OX3 9DUUnited [email protected]
Sergio Cerutti, MS, FIEEE, FIAMBEProfessor and Head of the Department of BioengineeringPolytechnic University in MilanoPiazza Leonardo da Vinci 3220133 [email protected]
Rory W. Childers, MDProfessor of Medicine/Director, Heart StationCardiology SectionDepartment of MedicineUniversity of Chicago Medical Center5758 South Maryland Avenue MC 9024Chicago, IL [email protected]
Andrea Colella, MDSenior PhysicianDepartment of Medical and Surgical Critical CareSection of Internal Medicine and CardiologyUniversity of Firenzev. le Morgagni, 8550134 [email protected]
Xavier Copie, MD, PhDConsultant CardiologistCentre Cardiologique du Nord32-36 rue des Moulins Gémeaux93200 [email protected]
viii Contributors
Otto Costantini, MDAssistant Professor of MedicineDirector, Arrhythmia Prevention CenterCase Western Reserve University @ MetroHealth MedicalCenterHeart & Vascular Center H-3342500 MetroHealth DriveCleveland, OH [email protected]
Philippe Coumel, MD, FESCConsultant CardiologistDepartment of CardiologyLariboisière Hospital2, rue Ambroise-Paré75010 [email protected]
Iwona Cygankiewicz, MD, PhDFellow of CardiologyInstitute of CardiologyHospital de Sant Pau i Santa CreuSt Antoni Ma Claret 16708025 [email protected]
Polychronis E. Dilaveris, MD, FESCResearch RegistrarDepartment of CardiologyUniversity of Athens Medical School22 Miltiadou Str155 61 [email protected]
Dwain L. Eckberg, MDProfessor, Medicine and PhysiologyMedical College of Virginia at Virginia CommonwealthUniversity 4614 Riverside Drive Richmond, VA 23225 [email protected]
Paul J. Erlinger, BSEEField Clinical EngineerCameron Health Inc.905 Calle AmanecerSuite 300San Clemente, CA [email protected]
Contributors ix
Ernest L. Fallen, MD FRCP(C) Professor Emeritus, Department of Medicine McMaster University Faculty of Health Sciences McMaster University Medical Center, Rm 3U8 1200 Main St. West HamiltonOntario L8N [email protected]
Shlomo Feldman, MD, FACCSenior Lecturer in CardiologyTel Aviv University.Past Director of the Pacemaker and Electrophysiology UnitHeart InstituteSheba Medical CenterTel Hashomer HospitalRamat Gan Israel [email protected]
Michael R. Franz, MD, PhD, FACCProfessor of Medicine and PharmacologyGeorge Town University Medical CenterDirector, Clinical and Experimental ElectrophysiologyVA Medical Center50 Irving St. NWWashington, DC [email protected]
J. Lee Garvey, MDMedical Director, Chest Pain Evaluation CenterDepartment of Emergency MedicineCarolinas Medical Center1000 Blythe BlvdCharlotte, NC [email protected]
Peter Geelen, MD, PhDCo-director, Arrhythmia UnitOLV Hospital, Cardiovascular Center Aalst164, Moorselbaan9300 [email protected]
Gian Franco Gensini, MDProfessor of Internal MedicineDepartment of Medical and Surgical Critical CareSection of Internal Medicine and CardiologyUniversity of Firenzev. le Morgagni, 8550134 Firenze, [email protected]
John E. Gialafos, MD, FESC, FACCProfessor of CardiologyDepartment of CardiologyUniversity of Athens Medical School37 Ipsilantou Street106 76 [email protected]
Andreas Grom, MDResearch FellowUniversitätsklinikum FreiburgInnere Medizin III, Kardilogie und AngiologieHugstetterstrasse 55D-79106 [email protected]
Roger Hainsworth, MB, ChB, PhD, DScProfessor of Applied Physiology and Honorary ConsultantClinical PhysiologistInstitute for Cardiovascular ResearchUniversity of LeedsLeeds LS2 9JTUnited [email protected]
Juha E. K. Hartikainen, MD, PhDSenior Consultant CardiologistDepartment of MedicineKuopio University HospitalBox 177770211 [email protected]
Harry Hemingway, MRCPReader in Clinical EpidemiologyInternational Centre for Health and SocietyDepartment of Epidemiology and Public HealthUniversity College London1-19 Torrington PlaceLondon WC1E 6BTUnited [email protected]
Katerina Hnatkova, MSc, PhD, FESCSenior Research FellowDepartment of Cardiac and Vascular SciencesSt George’s Hospital Medical SchoolCranmer TerraceLondon SW17 0REUnited [email protected]
Stefan H. Hohnloser, MD, FACC, FESCProfessor of MedicineDepartment of MedicineDivision of ElectrophysiologyTheodor-Stern-Kai 760590 [email protected]
B. Milan Horacek, PhDProfessor of BiophysicsDepartment of Physiology & BiophysicsDalhousie UniversitySir Charles Tupper Medical Building5859 University AvenueHalifax, Nova Scotia B3H [email protected]
Richard P.M. Houben, BScPrincipal Design EngineerAdvanced ConceptsMedtronic Bakken Research CenterEndepolsdomein 56229 GW MaastrichtThe [email protected]
Heikki Huikuri, MD, PhD, FACC, FESCProfessor in MedicineDepartment of Internal MedicineDivision of CardiologyOulu University Hospital, OuluPO Box 20FIN-90029 [email protected]
Bogdan G. Ionescu, MDFellow in CardiologyInstitute of CardiologyHospital de Sant Pau i Santa CreuSt Antoni Ma Claret 16708025 [email protected]
Juan Carlos Kaski, MD, DSc, FRCP,FACC, FESCProfessor of Cardiovascular ScienceDepartment of Cardiac and Vascular SciencesSt George’s Hospital Medical SchoolCranmer TerraceLondon SW17 0RE United [email protected]
x Contributors
Josef Kautzner, MD, PhD, FESCHead, Department of CardiologyInstitute for Clinical and Experimental MedicineVidenska 800140 21 Prague 4Czech [email protected]
Milos Kesek, MDConsultant Cardiologist Department of Cardiology Norrland University Hospital 901 85 UmeaSweden [email protected]
Robert E. Kleiger, MD, FACCProfessor of MedicineCardiovascular DivisionWashington University School of Medicine660 S. Euclid AveCampus Box 8086St. Louis, MO [email protected]
Paul Kligfield, MD, FACCProfessor of MedicineDivision of CardiologyWeill Medical College of Cornell University1300 York AvenueNew York, NY [email protected]
Maria Teresa La Rovere, MD, FESCDirector Autonomic LaboratoriesDepartment of CardiologyFondazione ‘Salvatore Maugeri’, IRCCSIstituto Scientifico di Montescano27040 Montescano (Pavia)[email protected]
Uwe Leder, MDCardiologistDepartment of Cardiology Clinic of Internal Medicine IIIUniversity of JenaErlanger Allee 10107740 [email protected]
Contributors xi
Jean-Yves Le Heuzey, MDProfessor of MedicineDepartment of CardiologyHôpital Européen Georges Pompidou20 rue Leblanc75015 [email protected]
Samuel Lévy, MD, FACC, FESCProfessorHopital Nord Cardiologie13015 [email protected]
Fred W. Lindemans, PhDGeneral ManagerMedtronic Bakken Research CenterEndepolsdomein 56229 GW MaastrichtThe [email protected]
Federico Lombardi, MD, FESCAssociate Professor of CardiologyCardiologia, Dip. di Medicina, Chirurgia e OdontoiatriaOspedale San Paolo, University of MilanVia A. di rudinì 820142 [email protected]
Robert L. Lux, PhDProfessor of MedicineCVRTI/Bldg 500University of Utah95 South 2000 EastSalt Lake City, UT [email protected]
Luca T. Mainardi, MS, PhDAssistant ProfessorDepartment of BioengineeringPolytechnic University in MilanoPiazza Leonardo da Vinci 3220133 [email protected]
Timo Mäkikallio, MD, PhDAssociate Professor of Experimental CardiologyDepartment of Internal MedicineDivision of CardiologyOulu University Hospital, OuluPO Box 20FIN-90029 [email protected]
Marek Malik, MSc, PhD, MD, DSc, DSc(Med),FACC, FESCProfessor of Cardiac ElectrophysiologyDepartment of Cardiac and Vascular SciencesSt. George’s Hospital Medical School Cranmer TerraceLondon SW17 0REUnited [email protected]
Alberto Malliani, MDHead of DepartmentDipartimento di Scienze Cliniche ‘Luigi Sacco’Ospedale SaccoVia GB Grassi 7420157 [email protected]
Rahul Mehra, PhDSenior Director, Atrial Fibrillation ResearchMedtronic, Inc.7000 Central Avenue N.EMinneapolis, MN 55432,[email protected]
Carl J. Meurling, MD, PhD, FESCConsultant CardiologistDepartment of CardiologyUniversity Hospital of LundSE-221 85 [email protected]
Antonio Michelucci, MDAssociate Professor of CardiologyDepartment of Medical and Surgical Critical CareSection of Internal Medicine and CardiologyUniversity of Firenzev. le Morgagni, 8550134 [email protected]
Nicola Montano, PhD, MDAssistant Professor of MedicineDipartimento di Scienze Cliniche “Luigi Sacco”Ospedale SaccoVia GB Grassi 7420157 [email protected]
Roger Moore, BSc (Hons), MBChB, MRCPCardiology Specialist RegistrarCardiothoracic CentreLiverpool L14 3PEUnited [email protected]
xii Contributors
Divaka Perera, MA, MBBChir, MRCPSpecialist Registrar in CardiologyDepartment of Cardiology6th Floor, East WingSt Thomas’ HospitalLambeth Palace RoadLondon SE1 7EHUnited [email protected]
Juha Perkiömäki, MD, PhDSenior Lecturer in Internal MedicineDepartment of Internal Medicine, Division of CardiologyOulu University Hospital, OuluPO Box 20FIN-90029 [email protected]
Massimo F. Piepoli, MD, PhD, FESCConsultant CardiologistCardiology DepartmentGuglielmo da Saliceto General HospitalCantone del Cristo29100 [email protected]
Paolo Pieragnoli, MDSenior PhysicianDepartment of Medical and Surgical Critical CareSection of Internal Medicine and CardiologyUniversity of Firenzev. le Morgagni, 8550134 [email protected]
Alberto Porta, MS, PhDResearch FellowLITA-Vialba, Department of Pre-Clinical SciencesUniversity in Milanovia G.B. Grassi 7420157 [email protected]
Esther Pueyo, BScLecturer in Biomedical EngineeringDepartment of Electronic Engineering and CommunicationsUniversity of ZaragozaMaria de Luna 150018 [email protected]
James Nolan, MBChB, FRCP, MDConsultant Cardiologist and Honorary Senior LecturerUniversity Hospital578 Newcastle Road, Stoke-on-TrentNorth Staffordshire ST4 6QGUnited [email protected]
Peter M. Okin, MD, FACCProfessor of MedicineDivision of CardiologyWeill Medical College of Cornell University1300 York AvenueNew York [email protected]
Walter H. Olson, PhDSenior DirectorImplantable DefibrillatorsMedtronic, Inc. B1737000 Central Avenue N.EMinneapolis, MN 55432-3576,[email protected]
S. Bertil Olsson, MD, PhD, FESC, FAHA, RPhSProfessor of CardiologyDepartment of CardiologyUniversity Hospital of LundSE-221 85 [email protected]
Luigi Padeletti, MDAssociate Professor of CardiologyDepartment of Medical and Surgical Critical CareSection of Internal Medicine and CardiologyUniversity of Firenzev. le Morgagni, 8550134 [email protected]
Sundip J. Patel, MBBCh, MRCPSpecialist Registrar in CardiologyDepartment of Cardiology6th Floor, East WingSt Thomas’ HospitalLambeth Palace RoadLondon SE1 7EHUnited [email protected]
Contributors xiii
Simon R. Redwood, MBBS, MD, FRCP, FACCConsultant CardiologistDepartment of Cardiology6th Floor, East WingSt Thomas’ HospitalLambeth Palace RoadLondon SE1 7EHUnited [email protected]
David Ritscher, MSPrincipal Scientist, Atrial Fibrillation ResearchMedtronic, Inc.7000 Central Avenue N.E.Mailstop B170Minneapolis, MN [email protected]
Maximo Rivero-Ayerza, MDClinical Fellow, ElectrophysiologyArrhythmia UnitOLV Hospital Aalst, Cardiovascular Center9300 [email protected]
Marten Rosenqvist, MD, PhDProfessor of CardiologyKarolinska Institutet,Stockholm Söder HospitalDepartment of Cardiology118 83 [email protected]
Juan Cosin Sales, MDResearch FellowDepartment of Cardiac and Vascular SciencesSt George’s Hospital Medical SchoolCranmer TerraceLondon SW17 0REUnited [email protected]
Alexander Schirdewan, MDCardiologistHead of the Department of ElectrophysiologyFranz-Volhard-Clinic BerlinHumboldt University BerlinWiltbergstrasse 5013125 [email protected]
Georg Schmidt, MDProfessor of Medicine1. Medizinische KlinikTechnische Universität Mü[email protected]
Raphael Schneider, Dipl. Ing. (FH)Software Engineer1. Medizinische KlinikTechnische Universität Mü[email protected]
Ulrich Schotten, MD, PhDAssistant Professor of PhysiologyDepartment of PhysiologyUniversity MaastrichtPO Box 6166200 MD MaastrichtThe [email protected]
Paul Schweitzer, MD, FACCDirector, Cardiac Arrhythmia ServicesProfessor of MedicineAlbert Einstein College of MedicineBeth Israel Medical CenterMilton and Carroll Petrie DivisionFirst Avenue at 16th StreetNew York, NY [email protected]
Peter Smetana, MDCardiologistWilhelminenspital der Stadt WienDepartment of CardiologyMontleartstrasse 371160 [email protected]
Leif Sörnmo, MSEE, PhDProfessor of Electrical EngineeringDepartment of ElectroscienceLund UniversityBox 118SE-221 00 [email protected]
Phyllis K. Stein, PhDDirector, Heart Rate Variability LaboratoryCardiovascular DivisionWashington University School of Medicine4625 Lindell Blvd, Suite 402St Louis, MO [email protected]
Shlomo Stern, MD, FACC, FAHA, FESCProfessor Emeritus of MedicineHebrew University Department of CardiologyBikur Cholim HospitalPO Box 492Jerusalem [email protected]
Martin Stridh, MSEE, PhDResearcherDepartment of ElectroscienceLund UniversityBox 118SE-221 00 [email protected]
Aneesh Tolat, MDClinical Cardiac Electrophysiology FellowBeth Israel Deaconess Medical CenterDepartment of Medicine, Division of Cardiology330 Brookline Avenue, W/BA-4Boston, MA [email protected]
Marion VanDyck, MD, FACCDirector, Cardiology Outpatient ServicesClinical Instructor of MedicineBeth Israel Medical CenterMilton and Carroll Petrie DivisionFirst Avenue at 16th StreetNew York, [email protected]
Richard L. Verrier, PhD, FACCAssociate Professor of Medicine, Harvard Medical SchoolBeth Israel Deaconess Medical CenterHarvard Institutes of Medicine4 Blackfan Circle, Room 223Boston, MA [email protected]
xiv Contributors
Giovanni Q. Villani, MDConsultant Cardiology, EP LaboratoryCardiology DepartmentGuglielmo da Saliceto General HospitalCantone del Cristo29100 [email protected]
Xavier Viñolas, MDChief of Electrophysiology LaboratoryInstitute of CardiologyHospital de Sant Pau i Santa CreuSt Antoni Ma Claret 16708025 [email protected]
Andreas Voss, PhDProfessor of Medical Informatics and Biosignal AnalysisDepartment of Medical EngineeringUniversity of Applied Sciences JenaCarl-Zeiss-Promenade 207745 [email protected]
Galen S. Wagner, MDAssociate Professor of MedicineDepartment of MedicineDuke University Medical Center2400 Pratt St., Room 0306Durham, NC [email protected]
Mari A. Watanabe, MD, PhDPostdoctoral Research AssociateInstitute of Biomedical Life SciencesGlasgow UniversityGlasgow G12 8QQUnited [email protected]
Dan Wichterle, MDClinical Electrocardiologist2nd Department of Internal Medicine1st Medical School, Charles UniversityU nemocnice 2128 08 Prague 2Czech [email protected]
Contributors xv
Shamil Yusuf, BSc (Hons), MbChB (Hons),MCOptom, MRCPResearch Fellow in CardiologyDepartment of Cardiac and Vascular SciencesSt. Georges Hospital Medical SchoolCranmer TerraceLondon SW17 0REUnited [email protected]
Markus Zabel, MDDirector of ElectrophysiologyDivision of CardiologyCharité - Campus Benjamin FranklinHindenburgdamm 3012200 [email protected]
Manfred Zehender, MD, MBA, FESCProfessor of MedicineUniversitätsklinikum FreiburgInnere Medizin III, Kardilogie und AngiologieHugstetterstrasse 55D-79106 [email protected]
The mysteries of the electrocardiogram unfold in the encyclopaedic tome, Dynamic Electrocardio-graphy, edited by Marek Malik and John Camm.Since the first published human electrocardio-gram was recorded in 1887 by Augustus Waller(Journal of Physiology 1887; 8: 229–234), ourunderstanding of cardiac arrhythmias and theelectrical manifestations of cardiac diseases hasburgeoned. Over the last several decades,advanced signal analysis and processing tech-niques have been applied to the electrocardio-graphic signal to extract increasingly importantinformation regarding cardiac physiology. Thesetechniques and their clinical importance arehighlighted in Dynamic Electrocardiography.
The editors have been extensively involved insetting the standards in many of the areas dis-cussed in the book. They fortunately providetheir expertise as both authors and editors. DrsMalik and Camm have also assembled an out-standing group of contributors, many of whomare the leading experts in their field. As with allnew developments, there are many applicationsand misapplications of these techniques. Theeditors have synthesized the topics so that thereader may focus on the technical details of howthe techniques are performed, how they areproperly applied, and what they might mean tothe clinician. This compendium therefore servesas an important resource to the clinician andresearcher. To our knowledge, there is no bookthat has the breadth of topics and the breadth ofappeal.
The book opens with a section on heart ratevariability. This section describes the multipletechniques that are used to measure heart ratevariability and puts into context how these mea-surements are to be interpreted. The ability toextract information regarding autonomic modu-lation of the heart rate from detailed signal pro-cessing techniques focused on characterizingsmall changes in heart rhythm has opened upmany areas of study. Because heart rate vari-ability measurements can be made noninva-
sively, much effort has been expended to betterunderstand what it means physiologically andprognostically. The ability of these measure-ments of heart rate variability to provide prog-nostic information regarding mortality,particularly in patients with cardiac disease, hasbeen an important contribution. The role of theautonomic nervous system in modulatingcardiac electrophysiology underlies its patho-physiologic link to sudden cardiac death. Furtherwork in this area will better define this link.Ongoing and future studies will provide the infor-mation necessary on how to use these tech-niques to better treat patients and improve theirsurvival.
Section II deals with measurement of barore-flex sensitivity and heart rate turbulence. Thesetechniques are used to measure the responsive-ness of the autonomic nervous system to a per-turbation, via the arterial baroreflex. Once again,the physiology, techniques, and clinical utility ofthese tests are described in this section. Thesemeasurements have been shown to be indepen-dent powerful predictors of mortality, even whencompared to standard heart rate variability mea-surements. Just as the exercise electrocardio-gram is a more useful test for the detection ofmyocardial ischaemia than the resting electro-cardiogram, so too these provocative manoeu-vres may provide additional information not obtained by resting measurements of autonomicmodulation.
Section III is devoted to evaluation of the STsegment for detection of myocardial ischaemiawith review of the underlying basic electro-physiology and clinical methods. Though ST seg-ment changes as a manifestation of myocardialischaemia have long been recognized, this re-presents a crucial area of electrocardiographywith important implications in patients withischaemic heart disease.
Section IV highlights the developments madein understanding ventricular repolarization andtheir impact on patients with cardiac disease.
Foreword
xvi
Foreword xvii
The complexities of ventricular repolarizationbecome apparent with the multiple ways thatexist to characterize it: the QT/RR relationship;circadian variation; QT dispersion; T wave morphology; and T wave alternans. The im-proved understanding from the cellular to thetissue level has led to the advanced application ofthese techniques. The chapters are very wellorganized to help guide the reader through themultidimensional approach to ventricular repolarization.
Sections V, VI, and VII deal with atrial fibrilla-tion, ventricular arrhythmias, and recordingsfrom implanted devices. These sections include
selected topics regarding electrocardiographictechniques with a specific focus on newer techniques.
This book will serve the reader as an importantreference for this broad array of topics. As thechapters are succinct and to the point, they willprovide the reader the most readily accessibleinformation in an easy to read format. Congrat-ulation to Drs Malik and Camm on a superbeffort.
Jeffrey Goldberger, MDMelvin Scheinman, MD
Compared to many clinical methods and proce-dures, electrocardiography is not particularlynew. The first human electrocardiogram wasrecorded by Dr Augustus Desiré Waller in 1887.Since that time, the development of electrocar-diography was not uniform. Several waves ofadvancement of the physiologic understandingand clinical utility of the electrocardiogram canbe traced throughout the past century. After thevery first human recording, it took about 20years for more precise equipment to be developedthat allowed recordings to be made with suffi-cient fidelity for meaningful biological interpre-tation. Another two decades elapsed before thevery core and principal rhythm abnormalitieswere appreciated and classified; it took somefurther decades to understand the ischaemic pat-terns in details; and so on.
The most recent wave of electrocardiographicadvances resulted from the observations that notonly the static snapshots of cardiac electricalactivity but also their temporal developmentcarry physiologically important and clinicallyuseful information. In many aspects, the investi-gation of this dynamicity of electrocardio-graphic recordings was not only facilitated butdirectly allowed by modern electronic and com-puting technologies. Indeed, it is inconceivable toimagine a modern electrocardiograph withoutsubstantial electronic and computer componentsaimed not only at recording the tiny electricalpotentials at the body surface but also at theirprocessing and detailed elaboration. Meaningfuland important electrocardiographic measure-ments and valuable clinical diagnoses reached inthis way frequently go far beyond the ‘classical’visual interpretation of the recorded images.
Because of the research and clinical impor-tance of this new window of electrocardiogra-phy, we were very pleased when asked byFutura/Blackwell to edit a comprehensive bookaimed at summarizing the most recent advancesin electrocardiography, concentrating primarilybut not exclusively on the dynamicity of the
recordings. The field of modern dynamic electro-cardiography is obviously rather broad. There-fore, we have divided the book into seven sectionsdealing with heart rate variability, baro-reflexes,dynamicity of ischaemic patterns, electrocardio-graphy of ventricular repolarization, atrial fibril-lation, ventricular arrhythmias, and finally therecordings made by an implanted device.
As with any other multi-author book, we facedthe usual editorial dilemma between having thebook tightly cross-referenced and having theindividual chapters suitable for stand-alonereading. We eventually felt that a volume of thissize should also serve as a reference textbook andthat having individual chapters as stand-alonereviews is therefore preferable. Consequently, weare happy to recommend the reader to select sep-arate chapters according to his/her particularneeds. Needless to say, reading the book in itsentirety will provide a more comprehensiveinsight into the recent advances in dynamic elec-trocardiography. In some areas of the field, therapid development in dynamic electrocardiogra-phy leads to occasional controversies. In suchcases, we tried to offer the reader the possibilityof learning and comparing the different views.
With a book of this broad spectrum, we ofcourse needed to rely on the help of others. Oursincere thanks therefore go to all the contribu-tors who helped us by writing individual chap-ters. We truly appreciate their efforts – withouttheir enthusiasms and kind involvement in theproject, the book would never have been written.We are also grateful to the publisher for carefultechnical editing of the text and for their under-standing and flexibility. Finally, our deep thanksgo to Mrs Pam Fernandes who helped us withrunning the editorial office of the book. It wouldhave been extremely difficult to organise thewhole volume without her meticulous involvement.
Marek MalikA. John CammOctober 2003
Preface
xviii
SECTION I
Heart Rate Variability
CHAPTER 1
Physiological Background of Heart Rate Variability
Roger Hainsworth
between vagal activity, which slows it, and sym-pathetic activity, which accelerates it (Levy &Martin 1979). Generally, if the rate is lower thanthe intrinsic rate of the pacemaker, it implies pre-dominant vagal activity, whereas high heartrates are achieved by increased sympatheticdrive.
Vagal responsesThe cell bodies of the vagal neurones lie in thedorsal motor nucleus and the nucleus ambiguus.The vagi run down the neck alongside thecarotid arteries into the thorax. These nervescarry not only the nerve fibres which controlheart rate but many other efferent nerves includ-ing those to the bronchi and the gastrointestinaltract. They also contain vast numbers of bothmyelinated and nonmyelinated afferent nervesinnervating thoracic and abdominal viscera.Activity in the vagal branches innervating thesinu-atrial node determines heart rate. Activityin nerves to the conducting mechanism re-duces its conduction velocity and high levels of vagal activity may completely block atrio-ventricular conduction. The question of vagalefferent activity on ventricular contractilityremains controversial. Earlier work indicatedthat in mammalian hearts inotropic responsesoccurred only in atrial and not in ventricularmuscle (Furnival et al. 1973). Confusion hasarisen due to the depressed atrial contractilitycausing reduced ventricular filling. Recent work,however, does point to the existence of a smallvagally mediated negative inotropic effect in the human ventricular myocardium (Casadei2001).
Introduction
Heart rate shows variations which are related,amongst other things to breathing, circadianrhythm and exercise. Resting heart rates can bevery different in different subjects, with somehaving rates of 100 beats/min and others only50 beats/min for no obvious reason. Highlytrained endurance athletes may have restingrates of only 40–50 beats/min with very largestroke volumes to compensate. The maximumrate is partly age-dependent with older subjectsachieving maxima during heavy exercise of20–30 beats/min less than those achieved byyounger individuals.
The rate of the heart and its beat-to-beat vari-ations are dependent on the rate of discharge ofthe pacemaker, normally the sinu-atrial node.The sinu-atrial node in turn is influenced byactivity in the two main divisions of autonomicnerves, which are controlled in a complex way bya variety of reflexes as well as by cortical factors.
This chapter will consider in turn the effects onthe heart of the autonomic nerves, the control ofautonomic activity by various reflexes, and theinteraction of these reflexes during some morecomplex events.
Effects of the autonomic nerves
In the absence of activity in sympathetic orparasympathetic nerves and with low levels of circulating hormones, particularly cate-cholamines, the heart will beat at its intrinsicrate of 100–120 beats/min. The rate at any particular time is determined by the balance
3
Electrical stimulation of either vagus nerveresults in slowing of the heart, and high fre-quencies of stimulation may result in asystoleand this may last several seconds. Often duringprolonged atrial asystole ‘escape’ beats may origi-nate from other parts of the conducting mecha-nism. In animals at least, stimulation of the rightvagus nerve seems to have a larger chronotropiceffect than that from left vagal stimulation(Hamlin & Smith 1968). Stimulation of the leftnerve has been reported to have a greater effecton A-V conduction and high frequencies causeA-V conduction block.
The relationship between vagal stimulationfrequency and the resulting change in heart rateis hyperbolic, with changes in frequency at lowheart rates having a much greater effect thanwhen the rate is high. However, vagal activitydoes not directly control heart rate but rather itacts to regulate the interval between successivebeats. If therefore, instead of plotting heart rate,we plot pulse interval against vagal stimulation,we see that the relationship becomes linearinstead of hyperbolic (Fig. 1.2). The choicebetween pulse interval and heart rate is largelyinfluenced by the interpretation that is required.If it is intended to be used to calculate cardiacoutput, then clearly heart rate is the appropriatevariable. If, however, we wish to quantitate avagal response, for example to a baroreceptorstimulus, then pulse interval should be used. The effect of this can be seen if, for example, achange in vagal activity induces a prolongationof pulse interval of 333 ms. At a heart rate of90 beats/min this would correspond to a rate
4 Chapter 1
change of 30 beats/min, but at 180 beats/minthe change in rate would be three times as muchat 90 beats/min.
Sympathetic responsesThe effect of vagal stimulation is very rapid. Asingle pulse has been reported to induce amaximal effect in only 400 ms (Levy et al. 1970).The significance of this is that heart rate can becontrolled through changes in vagal activity, on abeat-to-beat basis. The effect of vagal stimulationis to release the neurotransmitter acetylcholineand this has two effects on the pacemaker poten-tials. Firstly, the cells become hyperpolarized andsecondly, their rate of depolarization is decreased.Both effects prolong the interval before the criti-cal depolarizing threshold is reached (Fig. 1.1)
Cardiac sympathetic preganglionic nervefibres originate in the lateral grey horn of theupper thoracic region, synapse in the sympa-thetic ganglia, then form a plexus together withparasympathetic fibres over the mediastinum,before supplying all parts of the heart. Increas-ing the activity in cardiac sympathetic nerves is the principal way by which heart rate is
Fig. 1.1 Effects of vagal stimulation on pacemakerpotential. Note that there is an almost immediatehyperpolarization and a slower rate of depolarization.
Fig. 1.2 Effects of graded stimulation of efferent vagalnerve in the rabbit. Responses shown as heart rate( ) having a hyperbolic relationship with stimulusfrequency and as pulse interval ( ) with a linearrelationship. (Results obtained from data of Parker et al.1984, with permission.)
Physiological Background of Heart Rate Variability 5
increased above its intrinsic level. This isachieved by causing an increase in the rate ofdepolarization of the pacemaker cells, causingthe critical depolarization of the pacemaker cellsto be reached more rapidly (Fig. 1.3). Sympa-thetic activity, therefore, acts in a similar way tovagal activity in that it directly regulates thepulse interval rather than the heart rate. Theresponses differ from those to vagal stimulationin that they develop much more slowly. Follow-ing the start of stimulation, there is a latency ofup to 5s and then heart rate gradually increasesto reach a new steady level in 20–30 s. This isclearly of significance when considering heartrate variability and reflex responses. If a changeoccurs in response to a stimulation within 5 s ofits application the efferent mechanism can onlybe vagally mediated. Responses with longerlatencies are likely to be mainly sympathetic.
In addition to its effect on the sinu-atrial node,sympathetic fibres also influence the conductingmechanism and the ventricular myocardium.The right sympathetic nerves, at least in dogs,have a greater effect on heart rate whereas theleft nerves have a relatively greater inotropiceffect (Fig. 1.4). It should be noted, however, thatthe high levels of heart rate reached throughsympathetic activity can only be achievedbecause sympathetic activity also shortens theduration of ventricular systole. At rest, ventricu-lar systole lasts about 300 ms in a cardiac cycleof 800 ms. At high heart rates, when the entirecardiac cycle shortens to 300 ms, systolic timemust be reduced to allow time for filling.
Reflex control of heart rate
The efferent activity in both vagal and sympa-thetic nerves is regulated by the central nervous
system in response to excitatory and inhibitoryreflex inputs. Table 1.1 lists some reflexes respon-sible for decreasing or increasing the heart rate.The body, however, is influenced by many diverseinputs and the overall effect is dependent onoften complex interactions as well as corticalinfluences.
BaroreceptorsArterial baroreceptors exist in many regions ofthe body. Owing to their accessibility those in thecarotid sinuses have been most extensivelystudied, and in humans these are the only recep-tors capable of being selectively stimulated.Animal studies, however, have established poten-tially important baroreceptors in the aortic arch
Fig. 1.3 Effect of sympathetic stimulation on pacemakerpotential. Note the gradual increase in rate ofdepolorization and in rate of impulse generation.
Fig. 1.4 Comparison of the relative responses of heartrate and inotropic state (dP/dt max) to gradedstimulation of right and left sympathetic nerves. Notethe relatively larger effect on heart rate from the rightnerves. (Reproduced from Furnival et al. 1973, withpermission.)
Table 1.1 Reflex control of heart rate
Reflexes increasing Reflexes decreasing heart rate heart rate
Atrial receptors BaroreceptorsPulmonary stretch Chemoreceptors
receptors Ventricular chemosensitive Muscle metaboreceptors afferentsPain receptors Pulmonary ‘J’ receptors
Trigeminal afferents (diving)
(Hainsworth et al. 1970), the coronary arteries(Drinkhill et al. 1993) and in the abdominal circulation (Doe et al. 1996; Drinkhill et al.1997). Baroreceptors are stretch receptorswhich respond to changes in vessel transmural pressure. An important characteristic is theirresponse to changes in pulsatility. This enablesthem to respond to changes in cardiac strokevolume caused by changes in venous returnwhich may be too small to be detected as changesin pressure (Taylor et al. 1995). Baroreceptorsare effective at ‘buffering’ short-term changes inblood pressure. They are less effective in long-term pressure control due to their property ofresetting (Chapleau & Abboud, 1993).
Baroreceptors control blood pressure by theireffects on the heart and blood vessels. The imme-diate cardiac response is vagally mediated andoccurs very rapidly (Fig. 1.5). Eckberg (1978)applied brief stimuli to carotid baroreceptors bymeans of a neck suction device that increasedcarotid transmural pressure. He observed thatmaximal effects were obtained when a stimuluswas applied 750 ms before a subsequent antici-pated P wave. Baroreceptors, therefore, cancontrol heart period on a beat-to-beat basis. Variations in heart rate mediated through thebaroreflex can occur at relatively high frequen-cies. The actual frequency is dependent rather onthe variations in the stimulus than on latency ofthe reflex.
Baroreceptor reflex stimulus–response rela-tionships have a limited range of linearity. Thenonlinearity may be a feature of the effectormechanism. For example in resting conditionswhere sympathetic activity is low baroreceptor
6 Chapter 1
stimulation has little effect on vascular resis-tance, whereas unloading can cause an increasein resistance (Vukasovic et al. 1990). Cardiacresponses have different constraints. Stimulationat rest causes interval prolongation and unload-ing causes interval shortening. During exerciseor orthostatic stress, if little vagal activity ispresent baroreceptor unloading would beexpected to have a smaller effect.
It seems likely that the various baroreceptorgroups operate over different ranges of pressures.Coronary artery baroreceptors have been shownin the dog to have very low operating ranges andtherefore are suited to protect against hypoten-sion. (McMahon et al. 1996). Carotid and aortic receptors have higher operating ranges and can,therefore, stabilize both increases and decreasesin pressure.
ChemoreceptorsPeripheral chemoreceptors are situated incarotid and aortic bodies and are stimulated byasphyxia, i.e. hypoxia, hypercapnia and aci-daemia, as well as by severe hypotension. Undermost conditions their level of stimulation is lowand it is only during severe hypoxia or hypoten-sion that they become strongly stimulated. Themost obvious response to chemoreceptor stimu-lation is an increase in breathing. Their effects onthe cardiovascular system are complicated by theeffect on respiration. These effects are mediatedmainly through pulmonary stretch receptorsand, if this secondary modulation is prevented,carotid chemoreceptor stimulation leads to acardiac slowing (Fig. 1.6).
Trigeminal afferents: the diving reflexImmersion of the face or stimulation of trigemi-nal receptors by application of cold packs to theface elicits a diving reflex. This is very pro-nounced and of great importance to divingmammals. A response can also be seen inhumans (Daly 1985). This comprises apnoea,hypertension and bradycardia. The respiratoryarrest leads to asphyxial changes which stimu-lates chemoreceptors and further augments thebradycardia and vasoconstriction.
Cardiac and pulmonary nonmyelinated afferentsThe various cardiac chambers are extensivelyinnervated with nonmyelinated vagal afferents
Fig. 1.5 Responses of cardiac interval to stimulation ofcarotid baroreceptors in humans by neck suction. Anegative pressure applied to a lead chamber fitted overthe subject’s neck distends carotid baroreceptors andcauses an immediate prolongation of the interval.
Physiological Background of Heart Rate Variability 7
(Hainsworth, 1991a). Similar innervationextends to the lungs, the so-called J receptors(Paintal 1995). The most effective stimuli to anyof these nerves is injection of various noxiouschemicals such as veratridine, capsaicin andphenyldiguanide. The most sensitive intratho-racic region for chemical stimulation is the leftcoronary artery and minute injections of stimu-lating chemicals there can lead to a profoundbradycardia and hypotension (Fig. 1.7). Excita-
tion of these cardiac and pulmonary reflexesmay occur in humans following intravenousdrug administration or injection of radio-opaquedyes (Perez-Gomez & Garcia-Aguado, 1977).
The normal physiological role of cardiac andpulmonary nonmyelinated afferents seems to berelatively minor. Large changes in ventricularpressure may cause a transient stimulation ofventricular afferents, but pressures need to bebeyond those normally encountered (Drinkhill et al. 1993), and changes in coronary arterialpressure cause much larger responses. Similarlypulmonary nonmyelinated afferents are onlyexcited by chemical stimulation, pulmonary congestion or gross overdistension (Coleridge & Coleridge 1991). It is hard to disagree with the proposition that, although cardiac and pulmonary nonmyelinated afferents may beinvolved in disease processes, they do not have animportant regulatory role.
Atrial receptorsComplex unencapsulated nerve endings ofmyelinated nerve fibres are located mainly nearthe junctions between the venae cava and thepulmonary veins with the atria (Nonidez, 1937).They are responsible for what was originallyknown as the Bainbridge reflex. They are stretchreceptors and their discharge is linearly relatedto atrial volume and pressure. Because atrialfilling is dependent, amongst other things, onblood volume they are often thought of asvolume receptors.
Stimulation of atrial receptors induces anunusual pattern of responses (Linden &
Fig. 1.6 Responses to stimulation of carotidchemoreceptors in the dog by injection of 10 mg nicotinebitartrate into common carotid artery: (a) with lunginnervation intact; (b) following lung denervation. Notethe unmasking of the primary reflex bradycardia tochemoreceptor stimulation following lung denervation.(Reproduced from Hainsworth et al. 1973, withpermission.)
Fig. 1.7 The Bezold–Jarisch reflex.Veratridine (10 mg) was injectedinto the aortic root of ananaesthetized dog. This almostimmediately caused profoundbradycardia and vasodilatation,seen as a fall in perfusion pressureto a hind limb. (Modified fromMcGregor et al. 1986, withpermission.)
Kappagoda 1982; Hainsworth 1991b). Heartrate increases, but atrial receptors have little orno effect on vascular resistance in most regions.They do, however, target the kidney and increasesalt and water excretion through a reduction inrenal nerve activity and central inhibition ofvasopressin. In this way an increase in cardiacfilling leads to a diuresis and a natriuresis. Notethat these responses are reflexly mediated in thatnervous pathways are involved. They should notbe confused with the diuresis and natriuresisresulting from the release of atrial natriureticpeptide. This occurs in response to stretching ofcardiac myocytes and its physiological signifi-cance is uncertain.
Atrial receptors are likely to have an importantrole in circulatory control. However, the timecourse of any change needs to be considered in relation to its possible role in influencing heartrate variability. Because responses are mediatedthrough sympathetic efferents, following stimu-lation a period of 20–30 s is required for amaximal response. Atrial receptors, therefore,are unlikely to be important in mediating or modulating high frequency heart rate oscillations.
Heart rate changes during complex events
The foregoing has considered the effects ofchanges in stimuli to single discrete reflexogenicareas. This is of importance in analysing themechanisms which are involved but normal
8 Chapter 1
daily activities, including breathing, straining,changes in body position and various forms ofphysical exercise, result in changes in the stimu-lation of many diverse reflex mechanisms. Thissection is concerned with some of the morecommon activities which can affect the heartrate.
Sinus arrhythmiaSinus arrhythmia is caused by variations incardiac vagal efferent activity. Vagal activityoccurs only during expiration, being inhibitedduring the inspiratory phase (Fig. 1.9). Severalmechanisms seem to contribute. Reflexes fromthe low threshold pulmonary stretch receptors,which are also responsible for the Hering–Breuerreflex, almost certainly play a part (Hainsworth1974). However, sinus arrhythmia can be seen tosome extent in paralysed animals in absence ofbreathing movements and this has been attrib-uted to central connections between the respira-tory centres and the vagal nuclei (Anrep et al.1936). Baroreceptors are also likely to beinvolved as the variations in heart rate are alsoassociated with variations in blood pressure. Ithas been proposed that there is a central ‘gating’mechanism whereby during inspiration thebaroreflex is inhibited (Spyer & Jordan 1987).This concept is supported by the findings ofEckberg et al. (1980) who applied brief stimuli tothe carotid baroreceptors in humans andobserved maximal prolongation of pulse intervalduring expiration and almost complete inhibi-tion of the reflex in early inspiration (Fig. 1.10).
Fig. 1.8 Responses to stimulation ofatrial receptors. Receptors at thepulmonary vein–atrial junctions inanaesthetized dogs were stimulatedusing small balloons. This resultedin tachycardia (heart rate increasedby nearly 100 beats/min) but noperipheral vascular responses (nochange in pefusion pressure toperfused limb or in mean arterialblood pressure). (Reproduced fromCarswell et al. 1970, withpermission.)
Physiological Background of Heart Rate Variability 9
Sinus arrhythmia occurs with a period ofabout 4 s which is too fast for variations in sym-pathetic activity to be of major importance; it istherefore not unreasonable to consider the effer-ent limb of this response to be mainly if notentirely vagal in origin (Eckberg 1983; Fouad et al. 1984).
Postural changesIn humans moving from supine to motionlessstanding results not only in displacement of
blood into dependent capacitance vessels but alsoin a progressive transudation of plasma fluidacross dependent capillaries (Hainsworth 1999).This inevitably results in decreases in venousreturn and in pulse pressure. This and the alteredposition of carotid baroreceptors leads to com-pensatory reflex vasoconstriction and tachycar-dia. Because of the exquisite sensitivity ofbaroreceptors to changes in pulsatility meanblood pressure in the upright position is main-tained close to or even above that in the supineposition. If the orthostatic stress becomes toogreat, and in susceptible individuals this canhappen with relatively minor stresses, the vaso-constriction and tachycardia abruptly reverse tobecome vasodilatation and bradycardia (Fig.1.11). This was described by Lewis (1932) as avasovagal reaction indicating vasodilatation anda vagally mediated bradycardia. Occasionally,the bradycardia may extend to several seconds ofasystole. The mechanism switching off the sym-pathetic activity and turning on vagal activity isunknown. It was formerly thought to be theresult of a paradoxical stimulation of the ven-tricular receptor but this has now been shownnot to be the case (see Hainsworth 2003).
ValsalvaThe Valsalva manoeuvre involves strainingagainst either a closed glottis or an external resis-tance. Pressures within the thorax and abdomenare greatly increased, impeding the inflow of
Fig. 1.9 Respiratory sinusarrhythmia. Recording showsvariations in efferent vagal nerveactivity during respiratory cycle andduring changes in carotid sinuspressure. Note the cardiacacceleration during the phase ofinspiration associated withcessation of vagal activity. Activityis also influenced by changes incarotid sinus pressure, but theinspiratory inhibition persists.(Reproduced from Neil 1979, withpermission.).
Fig. 1.10 Influence of the phase of the respiratory cycleon the cardiac response to brief stimulation of thecarotid baroreceptors in humans using neck suction.Note the almost complete loss of the response duringearly inspiration. (Reproduced from Eckberg et al. 1980,with permission.)
blood from outside these regions. It is importantto note that, unlike positive pressure ventilation,blood does not pool in the abdomen. Fig.1.12shows effects of a controlled Valsalva and illus-trates the various phases. Firstly, the raisedintrathoracic and intra-abdominal pressurescompress the major vessels causing an abrupttransient pressure rise. Secondly, the reducedvenous return leads to a fall in cardiac outputand blood pressure. The pressure fall is compen-sated by reflex vaso-constriction and tachycar-
10 Chapter 1
dia. On releasing the Valsalva, the intrathoracicand intraabdominal pressures fall again decom-pressing the vessels and causing a transient fallin arterial pressure. The previously impededblood flows rapidly into the heart, and is pumpedout into a constricted circulation resulting in an overshoot of blood pressure and, often, bradycardia.
The Valsalva manoeuvre provides a test of theintegrity of the autonomic nerves and of thebaroreceptor reflex. Deficient reflexes result in
Fig. 1.11 Effects of orthostatic stress and the vasovagal reaction in a healthy human. During head-up tilting andparticularly during application of lower body negative pressure, there is a marked increase in heart rate with littlechange in blood pressure. Eventually, however, blood pressure falls and heart rate slows. (Reproduced from El-Bedawi &Hainsworth 1994, with permission.)
Fig. 1.12 The Valsalva manoeuvre.The four phases are seen: initialtransient increase in blood pressure;fall in pressure followed by recoverywith tachycardia; transient fall inpressure at the end of the strain;pressure overshoot and cardiacslowing.