contents · toshihisa anzai and satoshi ogawa cardiopulmonary division, department of medicine,...

Vol.45, No.4 April 2002

Acute Myocardial Infarction

● Key Points and Pitfalls in Electrocardiographic Diagnosisof Acute Myocardial Infarction

Toshihisa ANZAI and Satoshi OGAWA . . . . . . . . . . . . . . . . . . . . . . . . 135

● Present Status of Pre-hospital Thrombolytic Therapyfor Acute Myocardial Infarction—Its Indications and Problems—

Takeshi MOTOMIYA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143

● Complications of Acute Myocardial Infarction—Diagnosis and Treatment—

Hiroshi NONOGI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149

● Acute Coronary Syndromes

Hirofumi YASUE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155

Social Security

● Social Security Viewed from a Demographic Perspective:Prospects and Problems

Naohiro OGAWA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161

● Agenda for Japanese Social Security

Yoshinori HIROI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168

Recent Topics

● Adrenal Preclinical Cushing’s Syndrome

Toshihiro SUDA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172

● Characteristics of Multislice CT

Kazuhiro KATADA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175

CONTENTS

Correction: Error in Author NameIn the article titled, “Protein Restriction Diet as an Essential Tool in Treating Uremia: Myth or Truth?” published in the JMAJ Vol.45,No.2 (pp.80–83), and in the Correction which appeared at the foot of the contents page in the JMAJ Vol.45, No.3, the second author’sname was misspelled. The correct spelling of the author’s name is Tatsuo SHIIGAI. We apologize for the misspelling that occurred in theabove two issues.

JMAJ, April 2002—Vol. 45, No. 4 135

This article is a revised English version of a paper originally published inthe Journal of the Japan Medical Association (Vol. 125, No. 5, 2001, pages 665–670).

Key Points and Pitfalls inElectrocardiographic Diagnosisof Acute Myocardial InfarctionJMAJ 45(4): 135–142, 2002

Toshihisa ANZAI and Satoshi OGAWA

Cardiopulmonary Division, Department of Medicine,Keio University School of Medicine

Abstract: Since electrocardiographic features of acute myocardial infarction varytemporally and spatially among patients, there are many pitfalls in electrocardio-graphic diagnosis of this condition. In order to avoid overlooking acute myocardialinfarction, it is necessary to consider characteristic findings, such as augmentationof Twave amplitude, ST elevation, and the appearance of abnormal Qwaves, inlight of the time after onset. Observation of time-course changes allows us tononinvasively understand the presence/absence of recanalization and patho-logical conditions including infarct extension, infarct expansion, and retention ofpericardial effusion, as well as to three-dimensionally diagnose the infarct site fromchanges in waveform in various leads. The latter findings reflect the anatomy of theartery responsible for the infarction. In addition, it is possible to determine theinfarct site and the infarct-related artery from the waveforms of premature beats. Inrecent years, visualized diagnosis of coronary heart disease has become possibleby means of improved techniques including coronary angiography and intravas-cular ultrasound. However, it seems that the well-established qualitative diagnosisof myocardial infarction by electrocardiography will continue to be important.

Key words: Myocardial infarction; Electrocardiogram; Arrhythmia;Reperfusion therapy

an indisputable fact that electrocardiography(ECG) is the most important examination indiagnosing acute myocardial infarction. If acutemyocardial infarction is suspected from symp-toms and ECG findings, emergency treatment

Introduction

Although recent years have seen astonishingtechnological advances in the examination andtreatment of cardiovascular diseases, it is still

�Acute Myocardial Infarction

136 JMAJ, April 2002—Vol. 45, No. 4

T. ANZAI and S. OGAWA

ECG findings based on time after onset. If thepatient is in the hyperacute phase (within a fewhours after onset), ST elevation or depressionwill not necessarily be observed. It is importantto determine whether there is Twave ampli-tude augmentation. On the other hand, if thereare no ST changes or abnormal Qwaves 6 ormore hours after the onset, differentiation fromother diseases, particularly fatal disorders suchas acute aortic dissection, is necessary.

2. Importance of observing time-coursechanges

In addition to the importance of comparing theECG record taken at the emergency departmentvisit with the patient’s previous ECG record,subsequent frequent ECG recordings will alsoprovide important prognostic information.(1) Spontaneous recanalization and coronary

based on reperfusion therapy should be admin-istered as promptly as possible. However, elec-trocardiographic diagnosis is often difficult,such that some patients may not receive timelyreperfusion therapy during the acute phase ofthe disease.

The key points and pitfalls of electrocardio-graphic diagnosis of acute myocardial infarctionare described herein.

Time-course Changes inthe Electrocardiogram

1. Time after onset of chest pain andthe point of ECG reading

First of all, obtaining a full history is essentialto avoid overlooking acute myocardial infarc-tion. Second, ECG examination should be per-formed with adequate knowledge of possible

aVRaVR

aVL

aVF

aVL

aVF

V4

V3

V2

V1

V5

V6

V4

V3

V2

V1

a. On admission b. 3 days after onset

V5

V6

Fig. 1 ECG findings of impending cardiac rupturea.: ECG findings on admission. There is ST elevation in leads I, aVL, and V3–6, indicating myocardialinfarction of the anterolateral wall. b.: ECG findings at the time of shock occurring 3 days after onset.There is the evidence of atrial fibrillation. Leads I, aVL, and V3–6 show ST re-elevation with an upwardconvex pattern (infarct expansion), and all leads show decreased potentials (retention of pericardialeffusion). Subsequently, rapid retention of bloody pericardial effusion was noted.


ELECTROCARDIOGRAPHIC DIAGNOSIS OF AMI

vasospasm: If ST elevation is restored to thebaseline after visiting the outpatient clinic, it ispossible that spontaneous recanalization hasoccurred or that coronary vasospasm was in-volved in the heart attack. This should be con-firmed before thrombolytic therapy or emer-gency coronary angiography is performed.(2) Change from incomplete to complete occlu-sion of the infarct-related artery: Further incre-mental ST elevation suggests progression to com-plete occlusion due to thrombus formation. Inthis case, reperfusion therapy should be per-formed immediately.(3) Success or failure of reperfusion therapy:It is known that ST elevation is promptlyreversed (50% reduction within 1 hour) if throm-bolytic therapy is successful, i.e., recanalizationis achieved.1) It is also characteristic for negativeTwaves to appear in an early phase.2) Recently,coronary angioplasty has often been performedas an emergency treatment. Even if recanali-zation is achieved angiographically, microcircu-latory disturbances may persist (no-reflow phe-nomenon), causing prolonged ST elevation.(4) Infarct extension: Infarct extension occursif an intracoronary thrombus extends proxi-mally, and ST elevation may be recognized inother leads as well. This finding is said to berelatively common in obese women, after throm-bolytic therapy, as well as in those who havediabetes or non-Qwave myocardial infarction.(5) Infarct expansion: ST segment re-elevationoccurs if the area of vulnerable and necroticmyocardium is expanded by wall stress follow-ing transmural myocardial infarction. ST ele-vation in this case can be distinguished fromischemia in view of its upward convex form andpersistence over time.(6) Pericardial effusion: If infarction is com-plicated by pericarditis with pericardial effu-sion, low voltage in all leads will be observed.Subacute cardiac rupture occurring a few ormore days after onset often follows infarctexpansion or pericardial effusion. Therefore,these findings may facilitate predicting cardiacrupture to some extent (Fig. 1).

Changes in ECG Waveforms

1. Twave augmentation can easilybe overlooked

As mentioned previously, Twave augmenta-tion is one of the findings that may be over-looked in the acute phase. Since Twave aug-mentation is also present in early repolari-zation, hyperkalemia, left ventricular hyper-trophy, and left bundle branch block, differ-entiation from these conditions is necessary.Whereas such Twaves are bilaterally symmet-ric and narrow, hyperacute Twaves in myocar-dial infarction are often relatively broad andtheir peaks are located posteriorly rather thancentrally.

2. Possible diagnoses with ST elevationAcute myocardial infarction is the first diag-

nosis to be suspected if there is ST elevationtogether with chest pain. However, other possi-bilities should also be considered. In cases ofpericarditis, ST elevation is said to be relativelyslight, 0.5 mV or less, is not accompanied bymirror-image changes, and is observable in mostleads.

3. Diagnosis of the infarction siteAs shown in Table 1, it is possible to diagnose

the infarct site and the infarct-related artery onthe basis of which leads show ST elevation andabnormal Qwaves. However, the combinationof leads in which ST elevation and abnormalQwaves are observed varies somewhat accord-ing to individual coronary artery anatomy, anddoes not necessarily agree with the patternsshown in the table. Therefore, it is important tothree-dimensionally understand the infarct sitereflected in each lead (Fig. 2).

ST segment changes can often be observedin precordial leads in inferior infarction or inlimb leads in anterior infarction. The signifi-cance of such changes will be described below.(1) ST changes in the precordial leads in

inferior infarctionST depression: ST depression is seen in the


Table 1 Diagnosis of the Site of Myocardial Infarction

Infarct site Responsible coronary arterySites of abnormal Qwaves and ST elevation on ECG

I II III aVR aVL aVF V4R V1 V2 V3 V4 V5 V6

Anterior septum Proximal LAD � � � �

Apex LAD, RCA, or LCX � �

High lateral wall First diagonal branch of LAD � �

Anterolateral wall Proximal LAD including � � � � � �diagonal branch

Extensive anterior wall Proximal LAD � � � � � � � �

Anteroinferior wall LAD going around the apex � � � � � � �extensively

Lateral wall Diagonal branch of LAD, � � � �extending to the apex

High posterior wall LCX � �

LCX (including obtusemarginal branch)

Posterolateral wallLCX (large obtuse

� � � �marginal branch)

Posteroinferior wall LCX or large RCA � � � � �

Inferior wall apex RCA or LCX � � � � �

Inferior wall RCA or LCX � � �

Inferior wall/right ventricle RCA, before bifurcation of � � � �the anterior branch

Notes: � denotes Rwave augmentation or ST depressionLAD: left anterior descending artery, RCA: right coronary artery, LCX: left circumflex artery

V1

V2

V3V3

V4 V5 V6

V1

V1

aVF

aVL

I

II

III

AS

SPS

PWPW

LW LW

AW

AW

V1

LW LW

AW

AW

Fig. 2 Site of myocardial infarction and ECGLeads V1–V4 correspond to the anterior wall (AW) and septum (AS, S), and leads II, III, andaVF correspond to the left ventricular posterior wall (PW) to the posterior septum (PS). LeadsI and aVL correspond to the left ventricular free wall, and have enantiomorphic relations withleads II, III, and aVF because of their contralateral location. Although there are no availableleads directly facing the high posterior wall or lateral wall (LW), changes at these sites appearas mirror-image changes in leads V1–V4. Leads V5–6 correspond to the left ventricular apex.(Original illustration by Ogawa, S.)



precordial leads in about half of all patients withinferior infarction. The prognosis is reportedlypoor if ST depression persists. This is probablybecause most such patients have multi-vesseldisease involving the left anterior descendingartery or extensive inferior infarction involvingthe high posterior wall (ST depression occursin leads V1–V3 as a mirror-image change repre-senting transmural infarction in the lateral wall[LW] of the base of the heart, as shown in Fig.2).3,4) In particular, when ST depression in theprecordial leads is as severe as 3 mm or more,it is strongly suspected that the left anteriordescending artery is also affected.5) ST depres-sion in leads I and aVL in inferior infarctionrepresents mirror-image changes against STelevation in leads II, III, and aVF (the posteriorwall [PW] and the anterior wall [AW] at thebase of the heart in Fig. 2 are enantiomorphic).

ST elevation: ST elevation may be found inleads V1 and V2 in less than 10% of patientswith inferior infarction. This finding is knownto suggest the presence of right ventricularinfarction.6) Anterior infarction is different fromright ventricular infarction in that the degree ofST elevation is greater in lead V2 than in lead

V1 (V1�V2) in the former whereas it is greaterin lead V1 than in lead V2 in the latter (V1�V2)(Fig. 3). However, the finding associated withthe highest sensitivity and specificity in the diag-nosis of right ventricular infarction is ST eleva-tion of 1 mm or more in the right precordiallead (V4R).7) In cases of inferior infarction accom-panied by a blood pressure decrease, particu-larly when there is no angina preceding theinfarction, right ventricular infarction is alsofrequently present.8) Therefore, ECG findingsin the right precordial lead should always beconfirmed.(2) ST changes in the limb leads in

anterior infarctionST depression: It is said that, if there is ST

depression in the limb leads in anterior infarc-tion, multi-vessel disease is highly probable andthe prognosis is thus poor.9) However, STchanges in the inferior wall lead in anteriorinfarction are defined by the sum total of mirror-image changes (ST depression) in response toischemia of the anterior wall and changes dueto ischemia of the inferior wall (ST elevation).Therefore, if the left anterior descending arteryperfuses an extensive area ranging from theapex to the inferior wall, ST changes in the limbleads may be counterbalanced by mirror-imagechanges in the anterior wall, such that STchanges may appear to be absent or ST ele-vation may occur. On the contrary, if the leftanterior descending artery perfuses a limitedarea, prominent ST depression is often seen inleads II, III, and aVF.10)

ST elevation: In infarction of the left ante-rior descending artery long enough to go aroundthe apex of the heart as mentioned above, STelevation may be found in leads II, III, and aVF.When infarction has occurred in an area proxi-mal to the diagonal branch, ST elevation is alsoseen in leads I and aVL.(3) The infarct-related artery in inferior infarc-

tion (differentiation between the right coro-nary artery and the left circumflex artery):

It is sometimes difficult to electrocardio-graphically identify the infarct-related artery in

aVR

aVL

aVF

V4

V3

V2

V1

V5

V6

Fig. 3 12-lead ECG of right ventricular infarctionIn addition to leads II, III, and aVF, lead V1 also showsST elevation.



inferior infarction, because the anatomy of thecoronary arteries varies among patients. How-ever, a pure high posterior wall infarctionshowing Rwave augmentation alone (mirror-image changes) in lead V1 is a finding character-istic of myocardial infarction in the area of theleft circumflex artery, particularly its obtusemarginal branch (Fig. 4). If ST elevation is pre-sent in lead I and in at least one of the lateralwall leads (aVL, V5, V6), the lesion is presumedto be located in the left circumflex artery with asensitivity of 80% and a specificity of 90%.11)

4. Meaning of QwavesQwaves having a width of 0.04 sec or more

and corresponding to one-fourth of the voltageof Rwaves are regarded as abnormal Qwaves.This finding is particularly important in diag-nosing the infarct site in transmural myocardialinfarction. However, Qwaves can be induced byconditions other than infarction; the followingfindings are useful in differential diagnosis.12)

(1) Qwaves in lead aVL: Such Qwaves areoften found in the heart with a vertical axis.If there are no Qwaves with a width of0.04 sec in lead I or the left precordial lead,or if there is no abnormality in ST-T, myo-cardial infarction is unlikely.

(2) Qwaves in leads III and aVF: If there isQR in lead aVR, inferior infarction is highlyunlikely (the presence of rS in lead aVR

suggests inferior infarction).(3) Qwaves in leads V1-V3: The presence of

Qwaves only in leads V1-V2 is often seenin normal cases. If Qwaves are observed inleads V1-V3, anterior infarction should besuspected, but differentiation from leftventricular hypertrophy, left bundle branchblock, and chronic obstructive pulmonarydisease is necessary.

Arrythmia in Myocardial Infarction

1. Importance of premature beatsVentricular premature beats are often seen

in acute myocardial infarction. Observation ofthe waveform may provide important informa-tion for diagnosis. For instance, if there are pre-mature beats with a form of bifascicular block(left anterior hemiblock and right bundle branchblock) in inferior infarction, the origin of thepremature beats is considered to be the ische-mic site of the left posterior branch. However,since the left posterior branch is perfused byboth the left anterior descending artery and theright coronary artery, such premature beats areunlikely to occur in inferior infarction alone. Inthis case, multi-vessel disease involving the leftanterior descending artery and right coronaryartery or the presence of collateral flow fromthe right coronary artery to the left anteriordescending artery should be suspected.

2. TachyarrhythmiaVentricular tachycardia and ventricular fibril-

lation should always be borne in mind as a fatalarrhythmia possibly complicating myocardialinfarction. However, accelerated idioventri-

aVR

aVL

aVF

V4

V3

V2

V1

V5

V6

Fig. 4 ECG of high posterior infarctionECG recording 2 days after onset of infarction. Thereis Rwave augmentation, reflected by mirror-imagechanges in lead V1.



cular rhythm (AIVR) seen in about 50% ofreperfused patients13) is not an indication forantiarrhythmic drug therapy, because the rateis 50–120/min and does not influence hemo-dynamics. Ventricular tachycardia often beginsafter a ventricular premature beat, whereasAIVR begins after a long pause. In general,antiarrhythmic medication is given to patientswith warning arrhythmia characterized by 6 ormore distinct rhythms per minute, RonT, poly-morphism, and three or more serial rhythms.To manage potentially fatal arrhythmias suchas recurrent sustained ventricular tachycardiaor ventricular fibrillation in the chronic phaseof myocardial infarction, the use of an implant-able defibrillator should also be considered.

A type of supraventricular arrhythmia rela-tively frequently seen after myocardial infarc-tion is atrial fibrillation. In most cases, sucharrhythmia occurs transitorily with hemo-dynamic worsening, postinfarction pericarditis,or atrial infarction (as represented by elevatedPQ segment baseline on ECG) and disappearsspontaneously after resolving these problems.If there is hemodynamic disturbance due toatrial fibrillation, cardioversion should be con-sidered promptly. If transient atrial fibrillationis frequent in the chronic phase, the use of anti-arrhythmic drugs should also be considered.However, the possibility has been pointed outthat the prognosis may be worsened by inhibi-tion of cardiac function or by the proarrhyth-mic action of antiarrhythmic drugs.14) There-fore, prudent application of such medicationsis necessary.

3. BradyarrhythmiaIf atrioventricular block of Mobitz type II or

higher, bifascicular block, or symptomatic brady-cardia not responding to atropine is found aftermyocardial infarction, prompt insertion of anintravenous pacemaker is warranted. In thesecases of bradycardia, it is necessary to observethe QRS interval of the escape rhythm. If theventricular escape rhythm has a wide QRS,severe block involving up to the His bundle

is suspected, and a permanent pacemaker isoften required.

Conclusion

ECG changes in acute myocardial infarctionvary among different patients and may causedifficulties in diagnosis. However, it is possibleto ascertain the ongoing phenomenon accu-rately and without difficulty if one copes withwaveform changes in each lead in a flexiblemanner based on a full understanding of themeaning of such changes. Although cardiaccatheterization is now frequently used, andvisualized diagnosis of myocardial infarction isbecoming a common practice, the importanceof ECG should never been underestimated inlight of the qualitative diagnosis of myocardialinfarction.

REFERENCES

1) Shah, P.K., Cercek, B., Lew, A. et al.: Angio-graphic validation of bedside markers of reper-fusion. J Am Coll Cardiol 1993; 21: 55–61.

2) Matezky, S., Barabash, G.I., Shahar, A. et al.:Early Twave inversion after thrombolytic ther-apy predicts better coronary perfusion: Clini-cal and angiographic study. J Am Coll Cardiol1994; 24: 378–383.

3) Gibson, R.S., Crampton, R.S., Watson, D.D.et al.: Precordial ST-segment depression duringacute inferior myocardial infarction: Clinical,scintigraphic and angiographic correlations.Circulation 1982; 66: 732–741.

4) Hlatky, M.A., Califf, R.M., Lee, K.I. et al.:Prognostic significance of precordial ST seg-ment depression during inferior acute myocar-dial infarction. Am J Cardiol 1985; 55: 325–329.

5) Tendera, M. and Campbell, W.B.: Significanceof early and later anterior precordial ST seg-ment depression in inferior myocardial infarc-tion. Am J Cardiol 1984; 54: 994–996.

6) Geft, I.L., Shah, P.K., Rodriguez, L. et al.: STelevations in leads V1 to V5 may be caused byright coronary artery occlusion and acute rightventricular infarction. Am J Cardiol 1984; 53:991–996.

7) Klein, H.O., Tordijman, T., Ninio, R. et al.: The



trocardiographic differentiation of occlusionof the left circumflex vs. right coronary arter-ies as a cause of inferior acute myocardialinfarction. Am J Cardiol 1987; 60: 456–459.

12) Ogawa, S. and Akaishi, M.: Examination andtreatment of cardiovascular medicine: electro-cardiography. Cardiovascular Medicine Man-ual. Nankodo, Tokyo, 1995; pp.177–180. (inJapanese)

13) Cercek, B., Lew, A., Laramee, P. et al.: Timecourse and characteristics of ventriculararrhythmias after reperfusion in acute myo-cardial infarction. Am J Cardiol 1987; 60:214–218.

14) Cardiac Arrhythmia Suppression Trial: pre-liminary report: effect of encainide and fle-cainide on mortality in a randomized trial ofarrhythmia suppression after myocardialinfarction. N Engl J Med 1989; 321: 406–412.

early recognition of right ventricular infarc-tion: Diagnostic accuracy of the electrocardio-graphic V4R lead. Circulation 1983; 67: 558–565.

8) Haraphongse, M., Tanomsup, S. and Jugdutt,B.I.: Inferior ST segment depression duringacute anterior myocardial infarction: Clini-cal and angiographic correlations. J Am CollCardiol 1984; 4: 467.

9) Shiraki, H., Yoshikawa, T., Anzai, T. et al.:Association between preinfarction angina anda lower risk of right ventricular infarction. NEngl J Med 1998; 338: 941–947.

10) Fletcher, W.O., Gibbons, R.J. and Clements,I.P.: The relationship of inferior ST depres-sion, lateral ST elevation, and left precordialST elevation to myocardium at risk in acuteanterior myocardial infarction. Am Heart J1993; 126: 526–535.

11) Bairey, C.N., Shah, P.K., Lews, A.S. et al.: Elec-




Present Status of Pre-hospital ThrombolyticTherapy for Acute Myocardial Infarction—Its Indications and Problems —JMAJ 45(4): 143–148, 2002

Takeshi MOTOMIYA

Vice-Director, Tokyo Metropolitan Ohkubo Hospital

Abstract: Early administration of thrombolytic drugs for acute myocardial infarc-tion may improve survival if safely and appropriately administered. Delays to throm-bolytic reperfusion are substantial and are key factors in efforts to improve throm-bolytic strategies. Transportation delays vary depending on the patient’s distancefrom the hospital and availability of local ambulance system. In-hospital delay isalso a large single component of delay. Intuitively, pre-hospital initiation of throm-bolytic therapy is the most promising approach to reducing the overall time totherapy. A meta-analysis of 6 randomized controlled trials of pre-hospital versusin-hospital thrombolysis for acute myocardial infarction indicated significantlydecreased all-cause hospital mortality among patients treated with pre-hospitalthrombolysis compared with in-hospital thrombolysis. Estimated time to throm-bolysis was 104 minutes for the pre-hospital group and 162 minutes for thein-hospital thrombolysis group. However, the time savings can be offset in mostcases by an improved hospital triage with resultant “door-to-needle time” reducedto 30 minutes or less. Furthermore only a small percentage (5% to 10%) of patientswith chest pain in the pre-hospital setting have acute myocardial infarction and areeligible for thrombolytic therapy. For these reasons, a general policy of pre-hospitalthrombolytic therapy cannot currently be advocated and indicated only in caseswith transport time greater than 60 or 90 minutes as a Class IIb recommendationin the ACC/AHA Guidelines for the Management of Patients With Acute MyocardialInfarction.

Key words: Acute myocardial infarction; Coronary thrombolysis;Pre-hospital thrombolysis; t-PA

of acute myocardial infarction (MI) die within1 hour of onset of symptoms and before reach-ing a hospital.1) Coronary reperfusion therapy in

Introduction

Approximately one half of the patients died



T. MOTOMIYA

evolving acute MI is an established and effec-tive therapy for reduction of mortality and mor-bidity. More recent data regarding the time-dependent benefits of reperfusion therapy pro-vide added stimulus to develop more effectivemeans of expediting delivery of medical care topatients with acute MI. The reperfusion ther-apy is not limited just to the widespread useof thrombolytic agents, but also PTCA, stentand even emergency CABG surgery in suitablepatients. Currently PTCA and stent implanta-tion therapy is more frequently performed thanthrombolysis in Japan.

Delay in treating patients with acute MI is acritical factor in decreasing the overall survivalrate. Boersma et al.2) reported that the relationbetween treatment delay and mortality reduc-tion was expressed better by a non-linear thanlinear regression (Fig. 1), and the beneficialeffect of fibrinolytic therapy is substantiallyhigher in patients presenting within 2 hoursafter symptom onset compared to those pre-senting later. The components of delay fromonset to treatment are (1) patients related (i.e.,failure to recognize the seriousness of the symp-toms and delay in seeking medical attention);(2) pre-hospital evaluation, treatment, and trans-port times; and (3) time required for diagnosisand initiation of treatment in the hospital. Inmost cases, patient-related delay is the longest.Interventions to minimize patient delay are pri-marily educational in nature. As for the reper-fusion therapy, pre-hospital initiation of throm-

bolytic therapy may be the most promisingapproach to reducing the overall time to therapy.

In this article, randomized controlled trialsof pre-hospital versus in-hospital thrombolysisfor acute MI were reviewed and its indicationsand problems were discussed.

Indications and Contraindications ofThrombolysis

1. Indications of ThrombolysisRecent ACC/AHA guidelines3) are as fol-

lows; Class I (conditions for which there is evi-dence and/or general agreement that givenprocedure or treatment is beneficial, useful,and effective) are 1) ST elevation, time to ther-apy 12 hours or less, age less than 75 years, and2) bundle branch block and history suggestingacute MI. The earlier therapy begins, the betterthe outcome, with the greatest benefit decid-edly occurring when therapy is given within thefirst 3 hours; proven benefit occurs, however,up to at least within 12 hours of the onset ofsymptoms.

Class IIa (conditions for which there is con-flicting evidence and/or a divergence of opin-ion about the usefulness/efficacy of a proce-dure or treatment. And weight of evidence/opinion is in favor of usefulness/efficacy) is1) ST elevation, age 75 years or older. In per-sons older than 75 years, the overall risk ofmortality form MI is high without and withtherapy. Although the proportionate reductionin mortality is less than in patients youngerthan 75, the absolute reduction results in 10lives saved per 1,000 patients treated in thoseover 75.

Class IIb (usefulness/efficacy is less wellestablished by evidence/opinion) are 1) STelevation, time to therapy greater than 12 to 24hours, and 2) blood pressure on presentationgreater than 189 mmHg systole and/or greaterthan 110 mmHg diastole associated with high-risk MI.

Class III (conditions for which there is evi-dence and/or general agreement that a proce-

80

60

40

20

0Abs

olut

e be

nefit

per

1,0

00tr

eate

d pa

tient

s

0 3 6 9 12 15 18 21 24Treatment delay (h)

R2�0.25

R2�0.32

Fig. 1 Absolute 35-day mortality reduction versus treatmentdelay2)


PRE-HOSPITAL THROMBOLYTIC THERAPY

dure/treatment is not useful/effective and insome cases may be harmful) are 1) ST eleva-tion, time to therapy greater than 24 hours,ischemic pain resolved, and 2) ST-segmentdepression only.

Pre-hospital thrombolysis is classified as ClassIIb recommendation as pre-hospital throm-bolysis in special circumstances (e.g. transporttime greater than 90 minutes).3)

2. Contraindications and Cautions forThrombolysis

Bleeding represents the most important riskof thrombolytic treatment. Contraindicationsand cautions for coronary thrombolysis areshown in Table 1.3)

Thrombolytic Agents and Routs ofAdministration

All of the thrombolytic agents currentlyavailable are plasminogen activators. However,aside from this similarity, there are many differ-ences among agents in dose, circulating half-

life, fibrin-specificity, rates of coronary recanali-zation, risks of hemorrhage, and cost. Throm-bolytic agents available in Japan are urokinase,tissue plasminogen activator (alteplase, tiso-kinase, nateplase), pro-urokinase (nasaruplase),and mutant or modified plasminogen activator(monteplase, pamiteplase). Among them uro-kinase, tisokinase, and nasaruplase are approvedfor intracoronary use as well as intra-venoususe, but this intracoronary route of administra-tion for acute MI has been now less frequentlyperformed. Modified plasminogen activatorshave a longer half-life and can be administeredwith a single bolus intravenous injection.

Recent trials with alteplase have used anaccelerated or frontloaded dosing regimen.4)

Because the accelerated regimen leads to greaterearly patency rates without an increase inhemorrhagic risk, it has become the preferredmethod of administration in the United Statesand Europe. Modified t-PA monteplase has alsoproved to produce a higher rate of early recan-alization of the infarct-related coronary arterywithout fatal bleeding complications.5)

Table 1 Contraindications and Cautions for Thrombolytic Use in Myocardial Infarction3)

Contraindications• Previous hemorrhagic stroke at any time; other strokes or cerebrovascular events within

1 year• Known intracranial neoplasm• Active internal bleeding (does not include menses)• Suspected aortic dissection

Cautions/relative contraindications• Severe uncontrolled hypertension on presentation (blood pressure�180/110 mmHg)• History of prior cerebrovascular accident or known intracerebral pathology not covered

in contraindications• Current use of anticoagulants in therapeutic doses (INR�2–3); known bleeding diathesis• Recent trauma (within 2–4 weeks), including head trauma or traumatic or

prolonged (�10 min) CPR or major surgery (�3 wk)• Noncompressible vascular punctures• Recent (within 2–4 weeks) internal bleeding• For streptokinase/anistreplase: prior exposure (especially within 5 d–2 y) or

prior allergic reaction• Pregnancy• Active peptic ulcer• History of chronic severe hypertension


Pre-hospital Thrombolysis

In the randomized Seattle Myocardial Infarc-tion Triage and Intervention (MITI) study, car-diac function and infarct size were assessed inrather small number of patients who receivedeither in-field or in-hospital treatment witht-PA.6) Though the time savings for the pre-hospital thrombolysis conducted by paramedicsper se was small (about 30 minutes), treatmentinitiated in less than 70 minutes of onset ofsymptoms was found to result in a distinctadvantage in left ventricular function, infarctsize, and mortality. The larger European Myo-cardial Infarction Project (EMIP) study ran-domized 5,454 patients to pre-hospital versusin-hospital treatment with APSAC (anisoylatedplasminogen streptokinase activator complex)and assessed mortality outcome.7) Patients weretreated somewhat later in-field in EMIP (atabout 2 hours) than in MITI (about 1 hour),but about 1 hour was saved by in-field treat-ment compared with in-hospital therapy. Thisstudy showed a significant reduction of cardiacmortality and non-significant total mortality at1 month.

Morrison et al.8) reviewed randomized con-trolled trials of pre-hospital versus in-hospitalthrombolysis for acute MI and performed meta-analysis measuring in-hospital mortality in 6

randomized trials including MITI and EMIP(n�6,434). Results were similar regardless oftrial quality or training and experience ofthe provider among the trials and all-causemortality was significantly decreased in pre-hospital thrombolysis group as compared within-hospital group (Fig. 2). Estimated time tothrombolysis was 104 minutes for the pre-hospital group and 162 minutes for the in-hospital group. However, the time savings canbe offset in most cases by an improved hospitaltriage with resultant “door-to-needle time”reduced to 30 minutes or less. Furthermore,only a small percentage (5% to 10%) of patientswith chest pain in the pre-hospital setting haveacute myocardial infarction and are eligiblefor thrombolytic therapy. For these reasons,a general policy of pre-hospital thrombolytictherapy cannot currently be advocated andindicated only in cases with transport timegreater than 90 minutes as a Class IIb recom-mendation in the ACC/AHA Guidelines forthe Management of Patients with Acute Myo-cardial Infarction.3)

Choice of Agent

Three mega-trials randomizing a total 103,069patients have compared the effects on mortalityof various thrombolytic agents. In the Interna-

T. MOTOMIYAT. MOTOMIYA

Fig. 2 Results of randomized trials of prehospital thrombolysis on hospital mortality8)

Study

MITI, 1993

EMIP, 1993

GREAT, 1991

Roth et al., 1990

Schofer et al., 1990

Castaigne et al., 1989

Overall

360

5,469

311

116

78

100

6,434

0.69 (0.30–1.57)

0.86 (0.72–1.03)

0.56 (0.25–1.23)

0.80 (0.17–3.77)

0.46 (0.04–5.31)

0.74 (0.14–3.86)

0.83 (0.70–0.98)

No. ofPatients

OR (95% CI)Favors Prehospital

ThrombolysisFavors In-Hospital

Thrombolysis

0.91

0.85

0.78

0.65

0.63

0.48

QualityScore

ALL TRIALS


tional Study including GISSI-2 20,891 patientswere randomized to receive either strepto-kinase or alteplase.9) Mortalities at 30 days weresimilar (8.9% with streptokinase versus 8.5%with alteplase). The ISIS-3 trial randomized41,299 patients to receive either streptokinase,anistreplase, or duteplase.10) Mortality was simi-lar with all three thrombolytic regimen: 10.5%with streptokinase, 10.3% with duteplase, and10.6% with anistreplase. The GUSTO-I trialrandomized 41,021 patients to receive one offour thrombolytic regimens.11) The lowest mor-tality rate at 30 days (6.3%) was achieved withaccelerated administration of alteplase as com-pared with 7.2% for streptokinase. Why didISIS-3 and International Study fail to demon-strate any mortality difference between strepto-kinase and t-PA, as GUSTO-I trial did? Thefailure to use intravenous heparin in the formertrials may have disadvantaged alteplase in Inter-national Study and duteplase in ISIS-3. Sec-ondly a standard 3-hour infusion of alteplasehas been shown to produce less 90-minutepatency than an accelerated alteplase regimen,which delivers substantially more of the drug toaverage-weight patients in the first 60 minutes.

Recently the ASSENT-2 trial assessed theefficacy and safety of modified t-PA tenecte-plase compared with alteplase.12) Tenecteplaseand front-loaded alteplase were equivalent formortality. And the ease of administration oftenecteplase may facilitate more rapid treat-ment in and out of hospital. Similarly theInTIME-II trial demonstrated that 30 day mor-tality was equivalent but long-term mortalitytended to be lower in the nPA (lanoteplase)group as compared with accelerated alteplase.13)

Both of these agents have the advantage overalteplase of bolus intravenous administration,and therefore could easily be given in the com-munity or pre-hospital phase.

New Adjunctive Therapy

The disadvantage of thrombolytic therapyover primary angioplasty has been said to be a

PRE-HOSPITAL THROMBOLYTIC THERAPY

relatively low TIMI-3 flow of approximately50%. In the TIMI-14 study, however, TIMI-3flow was obtained in 77% at 90 minutes afterstart of the fibrinolytic regimen.14) The TIMI-14regimen consisted of half the standard dose ofalteplase, a low dose of intravenous heparin,monoclonal antibody of platelet glycoproteinIIb/IIIa receptor, abciximab, and aspirin. At60 minutes 65% of patients had TIMI-3 flow.These findings are significant since only 54% ofpatients given alteplase in the GUSTO-Iangiographic substudy15) had TIMI-3 flow at 90minutes, and since coronary angioplasty com-monly takes longer than an hour and a half ofcomplete.

REFERENCES

1) Report of a WHO Expert Committee: Servicefor Cardiovascular Emergency. WHO, Geneva,1975.

2) Boersma, E., Maas, A.C.P., Deckers, J.W. et al.:Early thrombolytic treatment in acute myo-cardial infarction: Reappraisal of the goldenhour. Lancet 1996; 348: 771–775.

3) ACC/AHA guidelines for the managementof patients with acute myocardial infarction.A report of the American College of Cardi-ology/American Heart Association task forceon practice guidelines (Committee on man-agement of acute myocardial infarction). J AmColl Cardiol 1996; 28: 1328–1428.

4) Neuhaus, K.-L., Feuerer, W., Jeep-Tebbe, S.et al.: Improved thrombolysis with a modifieddose regimen of recombinant tissue-type plas-minogen activator. J Am Coll Cardiol 1989; 14:1566–1569.

5) Kawai, C., Yui, Y., Hososa, S. et al.: A prospec-tive randomized double blind multi-centertrial of a single bolus injection of the noblemodified t-PA E6010 in the treatment of acutemyocardial infarction: comparison with nativet-PA. J Am Coll Cardiol 1997; 29: 1447–1453.

6) Weaver, W.D., Cerqueira, M., Hallstrom, A.P.et al.: Prehospital initiated versus hospital-initiated thrombolytic therapy. The MyocardialInfarction Triage and Intervention (MITI) trial.JAMA 1993; 270: 1211–1216.

7) The European Myocardial Infarction Project


T. MOTOMIYA

(EMIP) Group: Prehospital thrombolytic ther-apy in patients with suspected acute myocar-dial infarction. N Engl J Med 1993; 329: 383–389.

8) Morrison, L.J., Verbeek, P.R., McDonald, A.C.et al.: Mortality and prehospital thrombolysisfor acute myocardial infarction. A meta-analysis. JAMA 2000; 283: 2686–2692.

9) The International Study Group: In-hospitalmortality and clinical course of 20,891 patientswith suspected acute myocardial infarctionrandomized between alteplase and strepto-kinase with or without heparin. Lancet 1990;336: 71–75.

10) ISIS-3 (Third International Study of InfarctSurvival) Collaborative Group: A randomizedcomparison of streptokinase versus tissue plas-minogen activator versus anistreplase and ofaspirin plus heparin versus aspirin alone among41,299 cases of suspected acute myocardialinfarction: ISIS-3. Lancet 1992; 339: 753–770.

11) The GUSTO Investigators: An internationalrandomized trial comparing four thrombolyticstrategies for acute myocardial infarction. N

Engl J Med 1993; 329: 673–682.12) Assessment of the Safety and Efficacy of

New Thrombolytic (ASSENT-2) Investigators:Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarc-tion: the ASSENT-2 double-blind randomizedtrial. Lancet 1999; 354: 716–722.

13) Antman, E.M., Wilcox, R.G., Gingliano, R.P.et al.: Long-term comparison of lanoteplase andalteplase in ST elevation myocardial infarction:6 months follow-up in InTIME II trial. Circu-lation 1999; 100: I-498.

14) De Lemos, J.A., Antman, E.M., Gibson, C.M.et al.: Abciximab improves both epicardial flowand myocardial reperfusion in ST-elevationmyocardial infarction. Observations from theTIMI 14 trial. Circulation 2000; 101: 239–243.

15) The GUSTO Angiographic Investigators: Theeffects of tissue plasminogen activator, strepto-kinase, or both on coronary artery patency,ventricular function, and survival after acutemyocardial infarction. N Engl J Med 1993; 329:1615–1622.



Complications of Acute MyocardialInfarction—Diagnosis and Treatment—JMAJ 45(4): 149–154, 2002

Hiroshi NONOGI

Director, Division of Cardiology and Emergency Medicine,National Cardiovascular Center

Abstract: For the past 20 years, the in-hospital mortality rate of acute myocardialinfarction has significantly decreased to less than 10%. This reduction can beattributed mainly to the development of acute-phase treatment such as reperfusiontherapy. However, cardiogenic shock and cardiac rupture dominate more than 70%of the causes of death. CCUs have made efforts to treat these problems whosemortality rate is still high. For cardiogenic shock, maintenance of circulation fol-lowed by reperfusion therapy is necessary before it causes irreversible impairmentof organ function. For cardiac rupture, a critical care system should be establishedto implement emergency surgical intervention following the early detection of car-diac tamponade, in addition to the emphasis on prevention in high-risk populationsfor cardiac rupture.

Key words: Acute myocardial infarction; Cardiogenic shock; Cardiac rupture;Mortality; Complication

attributed to the progress of treatment of com-plications of acute myocardial infarction. Pumpfailure and cardiac rupture (including ventric-ular septal rupture) dominate approximately70% of the causes of death in the acute period.Prognosis has been improved, but the mortalityrate is still high. Therefore, CCUs are makingefforts to improve treatment effectiveness.1)

The diagnosis and treatments against the twomain causes of death will be discussed alongwith the major complications in the acute period

Introduction

The mortality rate of acute myocardial infarc-tion in our CCUs has decreased from 12% inthe early period (before the era of reperfusiontherapy, 1977–1986), through 8% in the middleperiod (thrombolytic treatment widely adopted,1987–1992), to 5% in the late period [PTCA(percutaneous transluminal coronary angio-plasty) adopted as the main reperfusion ther-apy, 1993–1998]. The improved prognosis can be



H. NONOGI

rate would not improve without reperfusioneven when using assisted circulation such asIABP (intra-aortic balloon pumping).

Cardiogenic Shock

1. Definitions (Table 3)Pump failure is defined as the condition in

which cardiac output is insufficient to perfusevarious body organs because of acute left ven-tricular contractile dysfunction caused by myo-cardial infarction. Cardiogenic shock is definedas myocardiogenic shock, except for when it iscaused by underlying diseases before the onsetof infarction, mechanical complications, andarrhythmia. Shock includes not only a low arte-rial blood pressure, but also severe, prolonged

Fig. 1 Serial changes of causes of death in acute myocardialinfarction (National Cardiovascular Center)

listed in Table 1.

Evaluation of the Severity

The classic Killip classification,2) one of theavailable methods for evaluating the severity ofacute myocardial infarction, is still helpful forthe estimation of prognosis. As shown in Table2, the severity can be easily judged from physi-cal findings according to the Killip classifica-tion. Killip et al. reported that the mortalityrate increased with the rise of the type of thedisease, and that mortality rate in class IV (car-diogenic shock) was as high as 81%. In ourfacility, the mortality rate was the same as thatof Killip-class IV before the era of reperfusiontherapy (Fig. 2), suggesting that the mortality

Table 2 Severity Classification of Acute Myocardial Infarction (Killip Classification)

Killip class Mortality rate inthe original article

Type I : no sign of CHF 6%(no rales in lung)

Type II : pulmonary congestion limited to basal lung segments 17%(bi basilar rales)

Type III: acute pulmonary edema 38%(rales in more than 50% of lung)

Type IV: cardiogenic shock 81%

CHF: congestive heart failure

Table 1 Major Complications of Acute Myocardial Infarction

1. Pump failure (cardiogenic shock, heart failure)2. Cardiac rupture (free wall rupture, ventricular septal

rupture, papillary muscle rupture)3. Arrhythmia4. Post-infarction angina5. Right ventricular infarction6. Pericarditis7. Left ventricular thrombus and complicated embolism

Cau

ses

of d

eath

Mortality rate

100

80

60

40

20

0

Pump failureCardiac ruptureVentricular septalrupture

1977�8612%

1987�928%

1993�985%

86 89

73

(year)

(%)


COMPLICATIONS OF ACUTE MYOCARDIAL INFARCTION

tissue hypoperfusion.3)

2. Treatment strategies4)

Because impairment of organ function causedby shock rapidly develops and becomes irre-versible within a short period, the most suitabletreatment should be adopted as early as possible.Prolonged tissue hypoperfusion makes prognosisworse, leading to death from multiple organ fail-ure even if hemodynamics is improved. Imme-diately after admission, respiratory controlshould be implemented for significant hypox-emia with the administration of catecholamines.If 5–20�g/kg/min of dopamine cannot achievepressor effects, 5–20�g/kg/min of dobutamine(DOB), or 0.05–0.2�g/kg/min of noradrena-line (NAd) should be administered.

At the same time, the femoral artery andvein should be secured with a 5 Fr sheath toenable use of assisted device at any time. Punc-turing is often difficult if the femoral artery isnot palpable. In principle, the internal jugularor subclavian vein should not be punctured incase of shock. The reason is that there are casesin which even one or two mispunctures canlead to fatal bleeding because of thrombolytic

therapy or heparinization. If systolic pressuredoes not rise to more than 80 mmHg within 15minutes, assisted device should be implemented.

Treatment requiring a combination of reper-fusion therapy and maintenance of peripheralcirculation is continued while in transit fromthe emergency room (or CCU) to the catheteri-zation room. The reperfusion method of choiceis PTCA. Prolonged shock with unavailabilityof a catheterization room should be treatedwith intravenous thrombolysis.

3. Assisted devices(1) Intra-aortic balloon pumping (IABP):

The results of IABP treatment without reper-fusion therapy for cardiogenic shock in acute

Fig. 2 Serial changes of the mortality rate of acute myocar-dial infarction (National Cardiovascular Center)

Table 3 Definitions of Cardiogenic Shock

1. Systolic pressure: less than 90 mmHg2. Existence of tissue hypoperfusion

(1) oliguria (less than 20 ml/h)(2) mental obtundation(3) peripheral vessel contraction (cool, clammy skin,

cyanosis)

Exceptions: hypotension accompanying conditions such aschest pain, hypotension of parasympatheticnerves (bradycardia-hypotension syndrome:Bezold-Jarisch reflex), arrhythmia, drug abuse,hypovolemia (e.g. dehydration and long-termadministration of diuretics).

Fig. 3 Medical guidelines for cardiogenic shock in acutemyocardial infarction support

IABP: intra-aortic balloon pumping, PCPS: percutaneouscardiopulmonary system, PTCA: percutaneous transluminalcoronary angioplasty.

Hearttransplantation

Medicationscatecholamine

From the emergency roomto the catheterization room

Respiratory controlIABP, PCPS

Successful reperfusionThrombolysis, PTCA

Coronary artery bypass surgeryLeft ventricular assist device

Mor

talit

y

100

80

60

40

20

0Killip-I

(2,361 cases)Killip-II

(439 cases)Killip-III

(216 cases)

4 4 ＊2

1215

9

22

1511

82

＊＊55

＊＊40

Killip-IV(183 cases)

1977�86 year1987�92 year1993�98 year

＊

＊＊ p�0.05 vs 1977�86p�0.01

（%）


myocardial infarction have not been encourag-ing. However, IABP is still an indispensableassisted device method when combined withreperfusion therapy. If systolic pressure is lessthan 80 mmHg, and cardiac index is less than2.2 l/min/m2 even with catecholamines, IABPshould be used. IABP serves as a pressure-support device, supporting only 15% of cardiacoutput. Therefore, if cardiac output by ownbeat cannot be expected, the following PCPSshould be used.

(2) Percutaneous cardiopulmonary supportsystem (PCPS): PCPS is a method in whichan artificial cardiopulmonary device enablingassisted circulation can be made available byinserting a cannula percutaneously. Perfusionis maintained by delivering oxygen to venousblood derived from right atrium by means ofan artificial lung, and by delivering the bloodretrogradually into the femoral artery (Fig. 4).It is possible to deliver blood at 2–4 l/min. If sys-tolic pressure is less than 50 mmHg, or repeatedventricular fibrillation or tachycardia requiringcardioversion is observed, PCPS should be used,rather than IABP. To support coronary perfu-sion, it should be combined with IABP.

Because PCPS should be implementedquickly, our CCU is always equipped with PCPS

with a circuit organized in sanitary conditions.In order to enable a few night staff members todeal with it, every nurse has routine training tocomplete circuit filling within 5 minutes as a partof lessons on cardio-pulmonary resuscitation.

If these types of assisted circulation andreperfusion are insufficient, the use of a leftventricular assist device to take care of part ofthe cardiac pumping function should be consid-ered. Because reduced cardiac function will beprolonged even after successful reperfusion,assisted circulation should be continued. Inten-sive care is required to maintain assisted circu-lation for a long period, and to prevent compli-cations such as infection, bleeding, and lowerlimb ischemia.

4. Efficacy of treatments for Cardiogenicshock

In cardiogenic shock, tissue hypoperfusion andacute myocardial infarction should be treatedat the same time. Failing in either treatmentwould be lethal. Reperfusion of occluded coro-nary artery is essential to improve prognosis.Moreover, it is important to achieve reper-fusion within a short period from the develop-ment of shock. If reperfusion cannot be achieved,the mortality rate is as high as 80% even with

H. NONOGI

Fig. 4 Percutaneous artificial cardiopulmonary system (PCPS)In case of a shock, 5 Fr sheath is inserted into femoral artery and vein to prepare for the initiation ofPCPS. Priming (circuit filling) is completed within 5 minutes. Routine training is required.

Inferior vena cava

Cannula for drawing blood Aorta

Cannula for bloodInjection of blood

Arterial side

Venous sideDrawing of blood Pump

Artifical lungheat exchanger

Right atrium


COMPLICATIONS OF ACUTE MYOCARDIAL INFARCTION

assisted device (Fig. 2). If a major vessel caus-ing occlusion is reperfused irrespective of thetype of reperfusion therapy, the in-hospitalmortality rate is less than 40%, suggesting theimportance of successful reperfusion.

A guideline of the ACC/AHA (AmericanCollege of Cardiology/American Heart Asso-ciation) strongly recommends the use of PTCA.5)

If PTCA is not available, or if it takes over 30minutes to start it, intravenous infusion of tis-sue plasminogen activator (t-PA) should be per-formed. However, because the mortality rate ofcardiogenic shock is still high, new therapiessuch as myocardial protection methods shouldbe reviewed in addition to reperfusion therapy.

Cardiac Rupture

Cardiac rupture occurs through an area oftransmural neurosis and expansion in the acutephase of myocardial infarction. It is classified asleft ventricular free wall rupture, ventricularseptal perforation or papillary muscle rupture,depending on the site of the lesions. The inci-dence of rupture shows two peaks: within 24hours after the onset of infarction, and oneweek later. The mortality rate of free wall rup-ture is high. It is one of the concerns for CCUsin parallel with death from pump failure. Thefrequency is low, but it does have a noticeableincidence. The frequency of the oozing type hasbeen increasing compared with the suddenrupture type, which is lethal and requires pre-ventive measures.

1. Free wall ruptureIn cases of successful reperfusion, the second

peak of cardiac rupture is reported to decrease,while the possibility of increased cardiac rup-ture caused by thrombolytic therapy is pointedout. Therefore, for patients over the age of 70complicated with hypertension, PTCA is oftenthe reperfusion method used.

Attention should be paid to suppress systolicpressure under 120 mmHg in the acute phaseof myocardial infarction, and under 20 mmHg

increase in the rehabilitation. Because patientsshowing significant retention of pericardial effu-sion in echocardiogram over time and patientswith rapidly thinning of the infarction wall arehighly susceptible to cardiac rupture, they arecarefully monitored and the rehabilitation pro-cess is delayed.

An oozing type of rupture with gradual reten-tion of bloody pericardial effusion leading tocardiac tamponade can be diagnosed by echo-cardiography before the patient goes into shock.Cardiac tamponade can be treated by perform-ing a surgical repair after drainage of pericar-dial cavity. A sudden rupture, which immedi-ately leads to electro-mechanical dissociation,is lethal. It is treated by PCPS immediately afterthe rupture to secure general circulation beforestepping up, but the prognosis for sudden rup-ture is unfavorable.

2. Ventricular septal perforationLike free wall rupture, the peak incidence of

septal rupture appears to be within a week afterinfarction. When a new, harsh, loud holosys-tolic murmur is heard between the third andthe fourth intercostal of the left parasternum,ventricular septal perforation is strongly sus-pected. It can be diagnosed by confirming theexistence of a left-to-right interventricular shuntusing two-dimensional echocardiography, andby confirming a significant increase in oxygensaturation from the right atrium to pulmonaryartery. The frequency of ventricular septal per-foration in our facility is approximately 1% ofall myocardial infarction. Out of 33 patients, 18underwent an operation, and 12 of them sur-vived and were discharged from the hospital.Only 2 out of 15 patients who did not undergosurgery survived and were discharged from thehospital. Therefore, the operation should beperformed whenever possible. Especially forshock, early surgical intervention is essential.

3. Papillary muscle ruptureSevere mitral regurgitation occurs after acute

myocardial infarction in papillary muscle rup-


H. NONOGI

ture, rapidly progressing to shock from left-sided heart failure. As cardiac murmur associ-ated with mitral regurgitation is brief or evencompletely absent in patients with reduced car-diac function, echocardiography is an effectivediagnostic tool. Because significant mitral regur-gitation is an indication to perform early sur-gical correction, valve replacement or repairshould be performed.

Conclusion

The prognosis for acute myocardial infarc-tion after admission has improved for the past20 years because of the progress in treatmentssuch as reperfusion therapy. However, as men-tioned in the present paper, the mortality rateof cardiogenic shock and cardiac rupture is stillhigh, and further efforts should be made toimprove treatment effectiveness. The mortalityrate before admission is higher, and 30–50% isestimated to die outside the hospital. Establish-ment of a cardiovascular critical care system isurgently required to reduce the general mor-

tality of acute myocardial infarction.

REFERENCE

1) Nonogi, H.: Therapeutic strategies to improvelong-term prognosis in acute myocardial infarc-tion. J Jpn Soc Intensive Care Med 1999; 6:189–195.

2) Killip, T. and Kimball, J.T.: Treatment of myo-cardial infarction in a coronary care unit. Atwo year experience with 250 patients. Am JCardiol 1967; 20: 457–464.

3) Nonogi, H.: Definition and diagnostic standardof cardiogenic shock. ICU and CCU 2000; 24:211–221. (in Japanese)

4) Residents of National Cardiovascular DiseaseCenter Eds: CCU Manual. Chugai Igakusya,2000. (in Japanese)

5) Ryan, T.J., Antman, E.M., Brooks, N.H., et al.:ACC/AHA guidelines for managements ofpatients with acute myocardial infarction:Executive summary and recommendations: Areport of the American College of Cardiol-ogy/American Heart Association Task Forceon Practice Guidelines (Committee on Man-agement of Acute Myocardial Infarction). Cir-culation 1999; 100: 1016–1030.



Acute Coronary SyndromesJMAJ 45(4): 155–160, 2002

Hirofumi YASUE

Director, Kumamoto Aging Research Institute

Abstract: Recently, unstable angina, acute myocardial infarction, and suddencardiac death have often been put together under the name “acute coronary syn-dromes”, because almost all of these conditions have been shown to be causedby thrombotic occlusion of a coronary artery following atherosclerotic plaque dis-ruption. Acute coronary syndromes occur more frequently in the coronary arterieswith no significant organic stenosis than in those with a high degree of stenosis. Aplaque prone to disruption has a thin fibrous cap, a large lipid core, and increasedinfiltration of macrophages and T lymphocytes. The elimination or control of riskfactors for atherosclerosis such as dyslipidemia, hypertension, smoking, diabetesmellitus, obesity, and lack of exercise is essential for the prevention of acute coro-nary syndromes.

Key words: Acute myocardial infarction; Atherosclerotic plaque;Coronary spasm; Coronary thrombosis; Unstable angina

between the two diseases. Angina pectoris isdivided into stable (organic) and unstable angina.The former is stable because advanced organicstenosis is extensively distributed in the coro-nary artery, but develops only when effortincreases oxygen demand. The latter developseven at rest and is characterized by the increasedseverity and duration of the attack and reducedresponse to nitroglycerin. The latter has beenconsidered to be at high risk of acute myocar-dial infarction or sudden death.

Recent studies have revealed that unstableangina, acute myocardial infarction, or ischemiccardiac sudden death develop mostly as a resultof plaque disruption in the coronary artery fol-lowed by thrombotic formation, thereby com-

Introduction

Ischemic heart diseases, including angina pec-toris and myocardial infarction, are the leadingcause of death in Europe and America. Theyhave also been increasing in Japan and arecurrently the second highest cause of death inthis country as the result of the westernizationof Japanese dietary habits, the increased useof automobiles, obesity, lack of exercise, andincreased stress induced by our complex society.

Angina pectoris develops by transient ische-mia of myocardium, while myocardial infarc-tion is the necrosis of myocardium caused byprolonged ischemia. It has therefore been con-sidered that a precise line should be drawn



H. YASUE

pletely or incompletely occluding the coronarylumen. Based on a similar onset mechanism,unstable angina, acute myocardial infarction,and ischemic cardiac sudden death have cometo be referred to collectively as acute coronarysyndromes.1–3) This concept was generated basedon rapid advances in clinical medicine, pathol-ogy, and molecular biology. At the same time,these advances force us to make a paradigmshift in the existing way of thinking about theseischemic heart diseases and the nature of thecorrective actions to be instituted.

Clinical Advances

The angina syndrome proposed by Heberdenincludes various diseases. James Herrick (1912)considered acute myocardial infarction to bean independent disease and inferred that itmight result from coronary occlusion by thrombi.Since then, coronary thrombosis has been con-sidered an important potential cause of myo-cardial infarction. In the 1970’s, however, therewere investigators, and pathologists in particu-lar, who believed that coronary thrombosis wasnot a cause of myocardial infarction. The almostsimultaneous introduction of coronary angio-graphy during the early stages of acute coro-nary infarction in major medical institutionsthroughout the world in the 1980s has allowedclinicians to identify the responsible artery.

The experience of the authors shows that theartery responsible for myocardial infarction wasspontaneously recanalized in the early stagesof the disease in 18% of the cases examined,and that it was recanalized by the intracoro-nary injection of nitroglycerin in 16%, and by athrombolytic agent (urokinase) in 46%.1) Theseresults indicate that most acute myocardialinfarction develop as a result of occlusion bycoronary thrombosis, and that coronary spasmalso causes myocardial infarction directly. Thethrombotic occlusion rate of the coronary arteryis higher in the earlier stages of the disease, andthe spontaneous re-canalization rate increasesover time.

It has been considered that coronary athero-sclerosis develops at an early age and pro-gresses slowly over several decades to causethe stenosis of the coronary lumen, and thatadvanced stenosis is prone to causing myocar-dial infarction. However, coronary angiogramsconducted prior to the attack of myocardialinfarction revealed that few cases had signifi-cant organic stenoses in the responsible coro-nary artery. Rather, myocardial infarction fre-quently occurs in the coronary lesions with nosignificant stenosis.1,4) A working group of theMinistry of Health and Welfare reported thatthe coronary artery responsible for myocardialinfarction had no significant stenosis before theonset of the disease in 86% of the patientsexamined. Improved intravascular echographyhas disclosed that most coronary arteries thatappear normal on angiograms have been affectedby atherosclerosis. It has also been shown thatplaque progress eccentrically toward the adven-titia and do not cause the stenosis of the lumenin the early stages of the disease. This has beenconfirmed by autopsy and is known as compen-satory growth.

Recent studies have indicated that reducingplasma cholesterol with hydroxymethyl glutarylCoA (HMG-CoA) reductase inhibitors mark-edly lowers the incidence of cardiovascular acci-dents, such as cardiac death and acute myocar-dial infarction, without producing significantchanges in stenotic lesions on coronary angio-grams. This suggests that the quality of plaquemay be more closely involved in the pathogen-esis of myocardial infarction than the degree ofcoronary stenosis.1–3)

Recent advances in coronary endoscopy andintravascular echography have revealed thatcoronary thrombi or plaque disruption fre-quently appear also in unstable angina.3–5)

Plaque Prone to Disruption

Advanced pathological techniques have re-vealed that the coronary lumen was occludedor narrowed by thrombi in most autopsied cases


ACUTE CORONARY SYNDROMES

with acute coronary syndrome, and that plaquehad been disrupted with fissures in approxi-mately two-thirds of such cases, and had beendisrupted with erosion in the remaining third.4,6)

The disrupted plaque showed inflammationwith the infiltration of macrophages and Tlymphocytes.

Plaque that is prone to disruption is charac-terized by (1) large lipid nuclei generated byfused lipids, such as cholesterol, accumulatedoutside the cells in plaque, (2) thin fibrous capthat separates lipid nuclei and vascular lumen,(3) increased infiltration of macrophages andT lymphocytes, and (4) a decreased numberof smooth muscle.3,4,6) The plaque is prone toundergo mechanical stress and disrupt at theborder between plaque and normal tissue,known as the shoulder, where a particularlylarge infiltration of macrophages occurs. Themechanical stress becomes stronger as thediameter of the lumen increases.

Since macrophages produce interstitial metal-loprotease that decomposes interstitial col-lagen and elastin, which are constituents offibrous caps, they make the caps thin and proneto breaking. Similarly, T lymphocytes secreteinterferon-� to inhibit the production of col-lagen from smooth muscle cells, thereby mak-ing the fibrous caps even more prone to break-age.3) Furthermore, the tissue factor, whichtriggers blood coagulation, is expressed inmacrophages and lipid nuclei. Therefore, onceplaque is disrupted to expose the tissue factorto blood, it activates blood coagulation cas-cades, which produces fibrin and thromboticformation.7)

Factors Precipitating Acute CoronarySyndromes

(1) Plaque disruptionIt has been shown that plaque disruption fol-

lowed by thrombotic formation is the origin ofacute coronary syndromes. ST-elevated myo-cardial infarction develops when thrombi com-pletely occlude the coronary lumen. When the

occlusion is incomplete, non-ST-elevated myo-cardial infarction or unstable angina develops.(2) Coronary spasm

Various factors other than plaque conditionmay induce acute coronary syndromes. Theonset of acute coronary syndromes tends todevelop in the early morning. This is related tothe circadian variation of blood coagulationand fibrinolysis systems and blood plateletaggregation. Blood is prone to coagulate, fibri-nolytic activity is reduced, and platelet aggre-gation is accelerated in the early morning.Coronary spasm tends to develop at night andin the early morning. When it develops, itincreases the tissue factor and fibrinopeptidein blood and reduces the fibrinolytic activity,thereby making it easier for thrombi to developand stimulating platelet aggregation. It is there-fore considered that coronary spasm triggersacute coronary syndromes through thromboticformation. Moreover, coronary spasm itselfcauses unstable angina and acute myocardialinfarction.1,8)

(3) StressStress triggers acute coronary syndromes

by increasing blood pressure to increase themechanical stress on plaque, by acceleratingblood coagulation and platelet aggregation,and by causing coronary spasm. It is wellknown that the incidence of acute myocardialinfarction increased in Israel after the GulfWar and in Hanshin after the Great HanshinEarthquake.

Pathogenesis and Treatments ofAcute Coronary Syndromes

1. Pathogenesis of acute coronary syndromesFigure 1 summarizes the pathogenesis of

acute coronary syndromes.1) Thrombi areformed after plaque disruption or coronaryspasm. Acute coronary syndromes developswhen the thrombi become sufficiently large toocclude the coronary artery. In some cases,coronary spasm may induce plaque disruptionor directly cause coronary occlusion. It is also


possible that a small artery running through theplaque is ruptured to cause a hemorrhage,which suddenly increases the size of the plaqueto mechanically occlude the coronary lumen.It is also known that thrombi cause coronaryspasm by serotonin or thromboxane A2 secretedfrom blood platelets.

2. Treatment of acute coronary syndromesSince the pathogenesis of acute coronary syn-

dromes is now well understood, it has becomepossible to apply appropriate treatment for thesyndromes. That is, acute coronary syndromesshould be treated by combining the treatmentsfor coronary thrombosis, spasm, and plaque dis-ruption. Among such treatments, the treatmentfor coronary thrombosis is most important.(1) Treatment for coronary thrombosis

Anti-platelet drugs, such as aspirin and ticlo-pidine, and anti-coagulants, such as heparin,are now most frequently used to treat coronarythrombosis. The effect of aspirin is relativelyweak and inhibits only one platelet coagulationpathway by thromboxane A2. Ticlopidine inhib-its the pathway through ADP (adenosine 5�-diphosphate), but may have adverse effects.

The GPIIb/IIIa (platelet glycoprotein IIb/IIIa) receptor antagonists, which block the com-mon final pathways of platelet aggregation,have recently attracted a great deal of atten-tion. Its efficacy and safety have been estab-lished via the many clinical trials conductedin Europe and America.1,9) It has been demon-strated to be particularly useful when intra-venously administered in percutaneous coro-nary interventions, such as percutaneous trans-luminal coronary angioplasty (PTCA). How-ever, the effectiveness of these anti-clottingagents when orally administered over longperiods have yet to be demonstrated. Its effi-cacy for acute coronary syndromes by an intra-venous route also remains controversial whenused without PCI.

Heparin is effective only when it combineswith antithrombin III, and is not effective forthrombin combining with fibrin. Heparin isinactivated by platelet factor 4. Therefore,hirudine and hirulog, which acts directly onthrombin, and low-molecule heparin with morestable activity have been studied in clinical set-tings. Clinical studies on activated protein C,which inhibits thrombotic formation, and the

H. YASUE

Fig. 1 Pathogenesis of acute coronary syndromesAcute coronary syndromes (unstable angina, acute myocardial infarc-tion, and ischemic cardiac sudden death) mostly result from coronaryocclusion by thrombi. However, in some cases they may develop dueto coronary spasm or mechanical occlusion by plaque disruption(quoted from Reference 1)

Coronary thrombosis

Coronary occlusion

Plaque disruptionCoronary spasm

Acute coronary syndromes

Unstable anginaAcute myocardial infarction

Ischemic cardiac sudden death


tissue factor pathway inhibitor (TFPI), whichinhibits the tissue factor itself, are also undergoing trials.

It has been established that thrombolytictherapy using tissue plasminogen activator (t-PA) or urokinase is effective for transmuralmyocardial infarction with elevated ST on ECG.PTCA or stent insertion without thrombolytictherapy is also performed for quick re-perfusion.However, it should be noted that thrombolytictherapy is ineffective for, or rather aggravatesunstable angina.1,9)

(2) Treatment for coronary spasmNitrates, calcium antagonists, and nicorandil

are effective for coronary spasm.1) Most caseswith unstable angina can be successfully con-trolled by these medications. However, somecases require percutaneous coronary interven-tion or coronary bypass. In such cases, PTCAitself can cause plaque disruption, therebyworsening acute coronary syndromes. There-fore, plaque in unstable angina that is prone tothrombi formation, should be stabilized bymedical therapy as far as possible beforePTCA. The recent introduction of stent inser-tion techniques has contributed to the preven-tion of acute coronary occlusion due to PTCAin a considerable number of cases.

3. Prevention of acute coronary syndromesAlthough various treatments for acute coro-

nary syndromes have been developed asdescribed above, it is still often difficult to treatthese syndromes once they develop. Therefore,preventing the syndromes is quite important.It is necessary to suppress atherosclerosis inorder to prevent acute coronary syndromesbecause atherosclerosis is the base of the syn-dromes. It is also important to eliminate or con-trol risk factors, such as hypertension, smoking,diabetes mellitus, hyperlipemia, obesity, andlack of exercise.10) The importance of eliminat-ing or controlling such factors was fully estab-lished by several multi-center prospective ran-domized studies which demonstrated that cor-recting hyperlipemia with HMG-CoA reduc-

tase inhibitors markedly reduced cardiovascu-lar events, such as acute myocardial infarctionand cardiac death.

Moreover, recent studies have shown thatthe following therapies are effective for pre-venting acute myocardial infarction and sud-den death: anti-platelet drugs, such as a smallamount of aspirin, anti-coagulants, such as war-farin, angiotensin converting enzyme (ACE)inhibitors, anti-oxidants, such as vitamin E,and estrogen replacement therapy for post-menopausal women.

Conclusion

Recent studies have revealed that most caseswith unstable angina, acute myocardial infarc-tion, or ischemic cardiac sudden death resultfrom coronary plaque disruption followed byformation of thrombi, which occlude or narrowthe coronary lumen. These diseases have there-fore come to be referred to collectively as acutecoronary syndromes. The syndromes are char-acterized by its frequent onset from mildly nar-rowed coronary arteries and easily disruptedplaque with large lipid nuclei, thin fibrous caps,together with marked infiltration of macroph-ages and T lymphocytes. Coronary spasm notonly triggers acute coronary syndromes, butalso occludes the coronary arteries to directlycause acute coronary syndromes.

Eliminating or controlling coronary risk fac-tors including hypertension, diabetes mellitus,smoking, hyperlipemia, and lack of exercise iscrucial for preventing acute coronary syndromes.Anti-platelet drugs, such as aspirin, and anti-coagulants, such as warfarin, are also useful.Calcium antagonists are effective for coronaryspasm.

REFERENCES

1) Yasue, H.: Pathogenesis and treatment of acutecoronary syndromes. Journal of Japanese Soci-ety of Internal Medicine 1998; 87: 296–301. (inJapanese)

ACUTE CORONARY SYNDROMES


H. YASUE

2) Fuster, V., Badimon, L., Badimon, J.J. et al.:The pathogenesis of coronary artery diseaseand the acute coronary syndromes. N Engl JMed 1992; 326: 242–250.

3) Libby, P.: Molecular basis of the acute coro-nary syndromes. Circulation 1995; 91: 2844–2850.

4) Falk, E., Shah, O.K. and Fuster, V.: Coronaryplaque disruption. Circulation 1995; 92: 657–671.

5) Mizuno, K., Satomura, K., Miyamoto, A. et al.:Angioscopic evaluation of coronary arterythrombi in acute coronary syndromes. N EnglJ Med 1992; 326: 287–291.

6) Davies, M.J.: Stability and instability: two facesof coronary atherosclerosis. Circulation 1996;94: 2013–2020.

7) Kaikita, K., Ogawa, H., Yasue, H. et al.: Tissuefactor expression on macrophages in coronaryplaques in patients with unstable angina.Arterioscler Thromb Vasc Biol 1997; 17: 2232–2237.

8) Oshima, S., Ogawa, H., Yasue, H. et al.: Fibrino-peptide A is released into the coronary circu-lation after coronary spasm. Circulation 1990;82: 2222–2225.

9) Braunwald, E., Antman, E.M., Beasley, J.W. etal.: ACC/AHA guidelines for the manage-ment of patients with unstable angina andnon-ST segment elevation myocardial infarc-tion. Circulation 2000; 102: 1193–1209.

10) AHA Medical/Scientific Statement: Guide toprimary prevention of cardiovascular diseases.Circulation 1997; 95 : 2329.


This article is a revised English version of a paper originally published inthe Journal of the Japan Medical Association (Vol. 124, No. 2, 2000, pages 207–212).The paper is a transcription of a presentation given at the JMA Health Policy Symposiumon Social Security held at the JMA office in Tokyo on February 5, 2000.

Social Security Viewed from a DemographicPerspective: Prospects and ProblemsJMAJ 45(4): 161–167, 2002

Naohiro OGAWA

Deputy Director, Population Research Institute,Professor, College of Economics, Nihon University

Abstract: This paper discusses the impact of population aging on the socialsecurity system, with particular reference to Japan. One of the primary findingsof this paper is that although coresidence has been considered for a long timeJapan’s latent asset in providing in-home care to the elderly, the demographicfeasibility of continuing such a care-giving pattern will be increasingly difficult inthe years to come, largely due to the low fertility trends persisting over the lastfew decades. In addition, norms of filial piety among middle-aged women havesubstantially weakened since the late 1980s.

Key words: Population aging; Social security system;Family organization; Value shift

benefits from the public pension system.In the first half of this paper, the relationship

between the aging of the Japanese populationand the social security system will be examined.The second half will deal with an analysis of theproblems the Japanese social security system islikely to face in the 21st century, from the view-point of the family.

As is well known, the Japanese social secu-rity system is wide-ranging, covering medicalcare, old-age pensions, and unemploymentcompensation programs. Among these pro-grams, it is the public pension system that dis-tributes income from the younger generations

Introduction

In the recent past, the birth rate in Japan hasbeen falling substantially, with the total fertilityrate for 1998 being 1.38 children per woman.Although this figure is not likely to fall belowthe 1.3 mark during 1999, it is considered almostcertain to drop to a historic low during theyear.

As the fertility rate continues to fall, debatesconcerning not only the long-term shortage oflabor but also the social security system aredisplaying a new intensity. This is particularlytrue of those relating to contributions to and

�Social Security


N. OGAWA

to the older ones to a substantial extent. Thus,when the age structure of the population shifts,this clearly affects the solvency of the pensionsystem.

In the medical care program, income flowsfrom the healthy to the ill. This latter groupdoes of course contain a significant proportionof elderly people, resulting in another flow ofearnings from the young to the elderly. How-ever, some young people also suffer from healthproblems, so that a certain amount of the flowis diverted back to the young themselves. Inthis manner, the medical care program inducesboth inter-generational and intra-generationalresource transfers.

It should be noted, however, that in the caseof the public pension system, methods of financ-ing play a part in determining whether or notchanges in age structure affect public pensionsystems. An example of a method not having aneffect in this way would be reserve financing.Some experts on the public pension system inJapan assert that in order to overcome thenegative effects of the aging of society, Japan’spublic pension system should be converted toreserve financing. At present though, pay-as-you-go components are predominant, and whenthis is the case, changes in age structures have adirect impact on the public pension system.

Clearly, in a country such as Japan, with itsrapidly aging population, there are major dif-ferences in the financial implications of agestructure shifts between the pension and themedical care systems. It should also be borne inmind that the effect of population age struc-tural change differs considerably, dependingon the methods of financing adopted for thesesocial security programs.

The Relationship Between MedicalCosts and Population Aging

First of all, let us compare a variety of coun-tries from around the world in terms of thepercentage of the population consisting ofpeople aged 65 and over and the percentage of

GDP taken up by health-related costs. Thiscomparison is based on OECD data for 1997.

As is clearly presented in Fig. 1, there appearsto be, broadly speaking, a positive correlationbetween these two variables. However, if wetake the U.S., Mexico, and South Korea out ofthe analysis, we find that this correlation is notstatistically significant; indeed, it is very closeto zero.

Looking at the way the figures for these coun-tries change over time, we can see that eachcountry conforms to one of three different pat-terns. As shown in Fig. 2, the countries showingthe first pattern include the U.S., Canada,France, Switzerland, and Greece. Here, the pro-portion of GDP taken up by health-relatedcosts increases along with the increase in theproportion of the elderly in the total population.

The second pattern, as displayed in Fig. 3,represents those countries where the ratio ofhealth-related costs to GDP shows little changeover time, of which Japan is one. Finally, thethird pattern corresponds to those countrieswhere health-related costs expressed as a pro-portion of GDP have actually fallen over time.This third pattern is shown in Fig. 4, and Den-mark, Ireland, and Sweden are some of thecountries which fall into this category.

Based on the cross-sectional and time-seriesdata presented so far, it is clear that the conclu-sion commonly arrived at with regard to aging,i.e. that the arrival of an aging society will beaccompanied by an increase in health-relatedcosts, is not necessarily valid. The reason forthis result lies in a number of factors affectingthe two variables in question. These include eco-nomic growth performance, political stability,and the tax system. Moreover, there is anotherimportant factor to be noted: the significantdifferences in family structures observed in thecountries sampled in the present study.

Take, for example, the second pattern, whichshows little change over time, and to whichJapan belongs. It should be clear that in spiteof this consistency over time, the proportion ofJapan’s population consisting of elderly people


SOCIAL SECURITY VIEWED FROM A DEMOGRAPHIC PERSPECTIVE

grew considerably over the time period underreview. The fact that relative health-relatedspending remained virtually unchanged overtime may be intimately linked with the advance-ment of the Japanese-style welfare system intro-duced in the 1970s by the Ohira administration.This point will be further discussed in the nextsection.

Limits to the Japanese-Style WelfareSociety

Figure 5 shows the changes in Japan’s totalfertility rate since World War II. Inspecting thisgraph reveals that the years 1947–1949 consti-tuted a so-called ‘baby boom,’ with an averageof 2.7 million births a year over that three-year

200

16

14

12

10

8

6

4

25 10

Population aged 65�(Percent)

15

Tot

al h

ealth

exp

endi

ture

as

a pe

rcen

tage

of g

ross

dom

estic

pro

duct

Source: OECD Health Data 99, OECD, 2000.

Sweden

United States

GermanySwitzerland

Canada

Mexico

Korea

Iceland

Spain

IrelandHungary Greece

CzechRepublic

Finland

United Kingdom

Netherlands

Italy

Australia

New Zealand

オーストリア

France

Japan

Denmark

Norway

BelgiumPortugal

Luxembourg

Austria

Fig. 1 Relationship between population aged 65 and over and total health expenditure


N. OGAWA

Fig. 3 Countries in which total health expenditure as apercentage of GDP is constant

Fig. 2 Countries in which total health expenditure as apercentage of GDP is increasing

Fig. 4 Countries in which total health expenditure as apercentage of GDP is decreasing Fig. 5 Trend in number of births in Japan

Tot

al h

ealth

exp

endi

ture

as

ape

rcen

tage

of g

ross

dom

estic

pro

duct


15

10

5

01980 1984 1988 1992 1996

Year

U.S.A. France GreeceSwitzerland Canada

Tot

al h

ealth

exp

endi

ture

as

ape

rcen

tage

of g

ross

dom

estic

pro

duct

15

10

5

01980 1984 1988 1992 1996

Belgium Japan U.K.Italy Netherlands


Year

Tot

al h

ealth

exp

endi

ture

as

ape

rcen

tage

of g

ross

dom

estic

pro

duct


15

10

5

01980 1984 1988 1992 1996

Year

Denmark Ireland Sweden

300

250

200

150

100

50

0

Million

194750

5560

6570

7580

8590

959899

Year

Source: Vital Statistics, various years.


period. Over the next several years, however,the fertility rate nearly halved, with the annualnumber of births falling to 1.5 million in 1957.

This was the first occurrence of such a phe-nomenon in the history of mankind, and waslargely responsible for inducing the aging ofthe Japanese population. Putting it differently,we may say that in that unprecedented 10-yearperiod when the total fertility rate nearly halved(1947–1957), Japan moved onto a course lead-ing to another historical first — the arrival ofthe first super-aged society, in the 21st century.

The 1978 Health and Welfare White Paper saysthat ‘coresidence is Japan’s latent asset.’ Thissuggests that Japan’s coresidence should some-how allow her to overcome various problemsarising from population aging. Will this obser-vation turn out to be valid, however, as familystructure undergoes a rapid transformation?

According to survey data gathered over aperiod of half a century by the Population Prob-lems Research Council of Mainichi Newspa-pers, the probability of adult children coresidingwith parents at the time they get married hasbeen decreasing. It is of interest to note thatthis trend goes hand in hand with the decreasein the proportion of arranged marriages; onecould say that changes in attitudes towardsmarriage and family organization have beendeveloping along similar paths. Particularlynotable is the way in which, as those coresidingwith the husband’s parents at the time of mar-riage have been becoming less common, thosecoresiding with the wife’s parents at this timehave actually been becoming slightly more so(figure not shown). It is quite conceivable that,within several years, those elderly coresidingwith a married daughter will become morenumerous than those living with a married son.This must be considered one of the most impor-tant changes with which Japanese society isfaced.

Next, let us turn our attention to care poten-tial as viewed from a demographic perspective.Taking the population aged 65–84 as the denomi-nator and the female population aged 40–59 as


the numerator, the demographic feasibility ofthe elderly being cared for by the female popu-lation they had given birth to can be examined.It should be mentioned here that these com-puted values are quoted not with the convic-tion that women should bear all the responsi-bility for taking care of the elderly, but due tothe fact that approximately 90% of all in-homecare for old persons is carried out by middle-aged women. These values have been computedfor a total of approximately 3,400 administra-tion units (cities, towns, and villages) through-out Japan since 1955.

The computed results (relevant graphs omit-ted) clearly show that the care potential ofmiddle-aged women fell between 1955 and1975 and again between 1975 and 1995. Indeed,in 1995, administrative areas in which thecomputed values were less than 0.5 increasedsignificantly.

Furthermore, the projected results for 2010suggest that the potential for caregiving on thepart of middle-aged women will decrease yetfurther, and those areas where the computedvalues are 0.25 or less will increase dramati-cally. In addition, the majority of the approxi-mately 3,400 areas are projected to have com-puted values below 0.25 in 2025.

As the numbers used for this calculation referto people already born, it can safely be said thatthese projected values are likely to be highlyrealistic. They therefore pose the question ofjust how practical the long-term care insurancesystem will be, and make absolutely clear howimportant it is to ensure that this problem isfully discussed at a range of political levels.

There is another key point to be dealt withhere. The United Nations’ 1998 population pro-jections suggest that the computed value forJapan as a whole will become lower than any-where else in the world during the period from2006 to 2018. This projected result can also beconsidered highly accurate for the reasons out-lined in the paragraph above.

Figure 6 shows the calculations of the burdendue to fall on full-time housewives looking after


N. OGAWA

19981950Year

Source: Calculated from various rounds of the National Survey on Family Planning.

90

80

70

60

50

40

30

20

10

0

Percent

1956 1962 1968 1974 1980 1986 1992

Expect to depend on children

“Good custom” or “Natural duty”

elderly persons who are bedridden or sufferingfrom senile dementia. It can be seen by inspect-ing the graphical presentation that the burdento be placed on those women in their 40s willrise quickly. At present, one out of every sevenor eight full-time housewives in their 40s takescare of a bedridden or senile elderly person. In2025, however, nearly 50% of this group areprojected to be in such a position. Needless tosay, these projected results suggest an extremelygloomy situation.

The burden will increase even more whenthe baby boom generation shift from being thecare providers to the care recipients. In otherwords, the current stage in the lifecycle of thebaby boom generation exerts a considerableeffect on the care needs of the country as a whole.

A point that needs to be mentioned here isthat those women who will be in their 40s in2025 consist of girls currently attending elemen-

tary school and junior high school. Whether ornot these girls will have the same values whenthey grow up as we do now remains to be seen.Therefore, changes in values are as crucialas population changes when considering thevarious problems related to caregiving in the21st century.

To shed some more light on this issue, let usexamine data collected from various rounds ofthe National Survey on Family Planning con-ducted by the Population Problems ResearchCouncil of Mainichi Newspapers. In each roundof the survey, the question ‘How would you feelabout looking after your elderly parents?’ wasasked to married women under 50. As seenin Fig. 7, from 1963–1986, 80% of Japanesewomen affirmed the practice, answering thattaking care of elderly parents was either ‘a goodcustom’ or ‘a natural duty.’ However, from 1988onwards, the corresponding figure has been

Fig. 7 Trends in norms and expectations regarding care forthe elderly: Japan, 1950–1998

Fig. 6 Projected ratio of the elderly population who sufferfrom senile dementia or are bedridden to non-workingwomen at various ages: Japan, 1995–2025

50

40

30

20

10

0

Percent

1995 2001 2007 2013 2019 2025Year

Source: Calculated by the author using the NUPRI long-term macroeconomic-demographic-social security model.

40~49

50~59

30～39歳30~39 60~69

20~29

70�



rapidly falling.It is conceivable that the reason for this sud-

den fall is the emphasis the government hasplaced on the creation of a new care systemsince the mid-1980s, in which in-home care playsa central role. Up until that point, the govern-ment had assumed the bulk of the responsibil-ity for looking after the elderly. Presumably,most of the married women asked thought thatthis would continue into the future, and itwould be sufficient for the family to providesupport for these efforts. However, with therelease of the White Paper on Health and Wel-fare in 1986, the government made clear thatit should not be relied upon to pay for nursingand other care, and the White Paper publishedthe following year stressed that the govern-ment would not be able to meet manpowerrequirements for providing care to the elderlyeither.

It seems fair to say that women were put in aposition where they were forced to change theiropinion of the merits of taking care of elderlyparents. In short, shifts in the concepts underly-ing the social security system were responsiblefor corresponding shifts in Japanese women’sattitudes relating to family nursing.

There is one more point made by Fig. 7 worthremarking upon. In the various rounds of theNational Survey on Family Planning, the follow-ing question was included: ‘Would you expectyour children to look after you in your old

age?’ The proportion of married women whoanswered that they would expect their childrento provide care in old age had been in long-term decline ever since Japan had started toexpand economically. In addition, in the early1960s, the proportion fell dramatically, due tothe implementation of universal pension andmedical care systems in 1961. It is well-knownthat old age security can play a large part in amarried couple’s decision to have children.When the new social security system was imple-mented, the motivation for having children wassharply reduced.

These time-series changes demonstrate howchanges in the social security system affectedboth fertility behavior and the criteria regard-ing how families look after their elderly mem-bers. It is clear that if our social security systemis not reorganized effectively in the 21st cen-tury, attitudes to family and in-home care willbe bent further still, perhaps to breaking pointor beyond.

REFERENCES

1) Ogawa, N. and Retherford, R.D.: Shiftingcosts of caring for the elderly back to familiesin Japan. Population and Development Review1997; 23: 59–94.

2) Retherford, R.D., Ogawa, N. and Sakamoto, S.:Values and fertility change in Japan. Dynamicsof Values in Fertility Change, Oxford Univer-sity Press, Oxford, 1999; pp.121–147.


This article is a revised English version of a paper originally published inthe Journal of the Japan Medical Association (Vol. 124, No. 2, 2000, pages 221–224).The paper is a transcription of a presentation given at the JMA Health Policy Symposiumon Social Security held at the JMA office in Tokyo on February 5, 2000.

Agenda for Japanese Social SecurityJMAJ 45(4): 168–171, 2002

Yoshinori HIROI

Associate Professor, Faculty of Law and Economics, University of Chiba

Abstract: Reform of Japan’s social security systems (health insurance, welfare,and pensions) has become a major issue as its population is rapidly growing older.This article examines Japanese Social Security in international perspective, andalong with identifying key features of its social security system, develops twodirections for reform: (1) Social security with emphasis on health care and welfare,and (2) social security based on support for individual life-cycles.

Key words: Japanese social security; International comparison;Models of social security; Health care and social security reform

Its features include a social insurance system,based largely around white collar and blue col-lar employees, and contribution-based benefitsparticularly in the case of pension system.

The third model (Model C in Table 1) is themarket model, of which the typical expression isin the United States. Public social security is keptto a minimum, the market or private insuranceis the main feature, and self-reliance, self-help,and volunteerism are expected to play a largerole.

These three models are linked to three typesof basic values and principles of social security.Model A places a high value on public support.The social insurance system of Model B in bothGermany and France emphasizes instead solidar-ity and mutual assistance, thus placing empha-sis on the notion of community The third model,Model C, the market model, is built on the

Three Models of Social Security

If we examine different social security sys-tems in countries around the world, we can findthree general models, or basic patterns, as shownin Table 1.

The first model (Model A in Table 1) is knownas the universalistic model, and is the typicalmodel in Sweden, other Scandinavian countriesand the United Kingdom. It is comprised ofsocial protections based primarily on generaltaxes, which covers all citizens (not only employ-ees), and is strongly grounded in the principleof equality.

The second model (Model B in Table 1) is thesocial insurance model, and as I will discuss later,it was the basic form of social security first intro-duced in Japan. The classic expression of thismodel can be found in Germany and France.

�Social Security


the social insurance pension system of Germanyor France, but more like a universalistic system.And all citizens take part in the basic pensionsystem which provides flat-rate benefits. Forhealth insurance, a separate old-age healthscheme was introduced in 1982 which was tocover both salaried employees and self-employed alike. At earlier times, the NationalHealth Insurance (Kokuho) program, which isa community-based health insurance for self-employed and farmers, was subsidized bynational general taxes for 50% of its spending,thus contributing to the realization of universalcoverage in 1961. All of these represent depar-tures from the original social in surance modelas seen in Germany and France.

principle of self-help and self responsibility.

Features of Japan’s Social SecuritySystem

Based on the assumptions listed above, thereare two noteworthy features in Japan’s socialsecurity system (see Table 2).

The first point is that social security in Japanis a “mixed” model. As mentioned before, theearly social security system in Japan was basedon the German social insurance model for bothhealth insurance and pensions, but then gradu-ally became more like a universalistic system.For example, the public basic pension (kisonenkin) system introduced in 1985, is not like

Table 1 Three Models of Social Security

Example

A. Universalistic model • General tax basis Scandinavian Countries,• All citizens covered (United Kingdom)• Principle of equality

B. Social Insurance model • Social insurance basis Germany, France• Employment-based coverage• Benefits based on income

C. Market model • Private insurance basis United States• Minimum public provision• Self-reliance, self-help, and volunteerism

• Differences in models are related to the idea of a spectrum ranging from self-reliance (Model C)to solidarity/mutual aid (Model B) to public support (Model A).

Table 2 Features of Japan’s Social Security System

(1) Mixed model• Japan developed from a social insurance model (Model B) gradually into a universalistic model (Model A)• The different principles of both models have been mixed, and the difficulty of resolving the two sets of basic

principles has grown (for example, in the public pension system)(2) Low spending on social security

• Spending on social security as a share of GDP reached 38.5% in Sweden by 1993, 27.9% in France, 25.3% inGermany, 21.1% in the United Kingdom, and 15% in the United States, but only 11.9% in Japan (and in 199613.4%)

• Why does Japan spend so little on social security?Reliance on “informal” social security, particularly corporate welfare based on life-long employment

• Currently, the community basis for this “informal” system (especially large corporations and the nuclear family)is falling apart quickly

AGENDA FOR JAPANESE SOCIAL SECURITY


What is important is that until recently, thismixed model has functioned rather well, but nowthe problems from conflicting principles havebecome much more serious. In other words, thecurrent system is not based on a clear philoso-phy or basic set of principles.

For example, the basic pension (kiso nenkin)uses a mixed finance, in which one-third of theprogram is financed by general tax revenue,and two-thirds by pension contributions. Thusit is not clear what kind of basic character thesystem has. Is it the kind of system in which theyoung support the old, since it is close to a tax-based system, or is it more of an insurancesystem, in which the money contributed whileyoung will be paid out later? Accordingly, thequestion of how to make the role of taxes andinsurance clear will be a major issue in settingthe future direction of the system.

Another feature of the Japanese social secu-rity system is that the level of spending on socialsecurity is quite low.

For example, if we compare the level of socialsecurity spending to GDP, Sweden, France, andother European countries have by far the high-est level of spending. Japan is even lower thanthe United States. It has been said that onereason for this gap is that aging has not pro-gressed as rapidly in Japan as in the other coun-tries, but in 2000, Japan became the most agedcountry in the world surpassing Sweden. There-fore, the difference in the rate of aging is notable to explain why social security spending in

Japan is so low.So we are left with the question of why the

level of social security spending in Japan is solow. I believe the answer lies in the fact thatsocial security in Japan has long relied in largepart on “informal support” provided by compa-nies and families.

In the system of lifetime employment inJapanese corporations, not only the employeesbut also their families are supported throughcompany benefits for family support and hous-ing. As a result, Japanese social security hascome to rely on corporations and families,and the level of social security spending hasremained low.

But if we look at the changing social condi-tions in Japan, we see that the corporations andnuclear families that underpinned this systemof informal support have rapidly become muchweaker. That is to say, the system of lifetimeemployment in large corporations has ended,and large-scale layoffs have become much morecommon. Within families, more and more womenwork outside their homes and family structureis becoming a more individualized one. There-fore, it is extremely important to discuss thepolicy response of the social security system tothe dissolution of the community in Japan.

Directions for the Future of SocialSecurity in Japan

Based on the previous points, it is possible to

Table 3 Future Directions in Social Security Reforms

(1) Social security with strong emphasis on health and welfare• Public support in areas of health and welfare, which is likely to have market failure• Restructuring and strengthening basic pension as a tax-based public pension

(2) Social security based on individual life-cycle• Towards an individual-based society, acknowledging more fluid labor market and growing female

workforce participation• More unemployment compensation and childcare support benefits• Clear division between tax and insurance

• Children and elderly—mostly tax-based (strong income redistribution character)• Adults (active labor force)—mostly insurance based

Y. HIROI


identify two possible directions for future socialsecurity reforms in Japan (see Table 3).

The first possible direction is a social securitysystem with a strong emphasis on health andwelfare, rather than pension.

In international perspective, the share of pen-sion benefits in Japan’s social security system isunusually high. From now resources should beshifted more into health care and welfare. Onereason for this is that if health care and welfareare left to the private market, they do not func-tion well as market failure is likely to occur inthese areas. On the other hand, market failureis less likely to take place in the area of pension,and so the pension system could be reduced toa basic public pension which provides minimumequal support, and supplemental income-basedpension might best be left to market provision.

But in this case, a stronger basic public pen-sion system would be required, and in order toassure a basic livelihood, tax rather than insur-ance revenues should properly play a role.

Another direction that the social securitysystem could take would be a system based onan individual life-cycle. As mentioned above,the labor market is becoming much more fluid,and women are working outside their homes ingreater numbers than ever before. As a result,individuals are becoming the basis of society,and a social security system that takes this intoaccount may become necessary.

Still another feature of the Japanese socialsecurity system is that there is almost no unem-

ployment compensation. In Europe, the levelof unemployment insurance is quite high, and itis possible that it will play a larger role in Japanin the future as well. The reason for this is thatunemployment benefits will be more importantas corporations become more flexible. And asfamily structures also become more flexible andsociety becomes more individualized, it will benecessary to improve child benefits. These ben-efits have been very low in Japan in comparisonto other countries, and both child care andunemployment benefits may have to becomemuch more generous than before.

Based on this discussion, while consideringthe principles of tax-based and insurance-basedsocial security, the total picture of social secu-rity is likely to take the following direction.

Supporting children and the elderly will bebased for the most part on taxes, since they areage groups which do not earn income, but at thesame time require the most health services andother benefits. Accordingly, insurance-basedsystem, which presupposes the balance betweenbenefits and contributions, is unlikely to be sus-tainable and so the tax-based system should beadopted. On the other hand, for the people ofproduction age, it would be most desirable tolink benefits and contributions more directlyso the insurance-based may be more desirableand efficient. In total, the future direction ofsocial security should be the one based on anindividual life-cycle.

AGENDA FOR JAPANESE SOCIAL SECURITY


Adrenal Preclinical Cushing’s SyndromeJMAJ 45(4): 172–174, 2002

Toshihiro SUDA

Professor, Third Department of Medicine, Hirosaki University School of Medicine

Key words: ACTH; Cortisol; Adrenal; Incidentaloma; Pituitary


Introduction

Cushing’s syndrome results from chronicglucocorticoid excess with characteristic clini-cal signs and symptoms. Cushing’s syndromeis divided into 2 groups, ACTH-dependentor ACTH-independent. Varieties of ACTH-dependent Cushing’s syndrome are Cushing’sdisease (primary hypersecretion of pituitaryACTH), ectopic ACTH syndrome (inappropri-ate secretion of ACTH from non-pituitarytumors), and ectopic CRH syndrome (inappro-priate secretion of CRH from non-hypotha-lamic tumors causing hypersecretion of pitu-itary ACTH). ACTH-independent Cushing’ssyndrome is caused from primary adreno-cortical disorders. They are adrenocorticaladenoma or carcinoma, ACTH-independentmacronodular adrenocortical hyperplasia(AIMAH), and primary pigmented micro-nodular adrenocortical dysplasia (PPMAD).

Incidentaloma of the adrenal gland is thenew endocrine epidemic as a result of a widerapplication of imaging techniques (CT, MRI,ultrasonography . . . etc.). About 10% of theadrenal incidentaloma secrete cortisol in atleast a partially autonomous condition (abnor-mal cortisol response to dexamethasone sup-pression test.1,2) These patients do not show

specific features of Cushing’s syndrome andare defined as having preclinical Cushing’syndrome. Adrenal preclinical Cushing’s syn-drome has the autonomic cortisol secretionthat is insufficiently abnormal to cause a clini-cally manifested Cushing’s syndrome.3,4)

Pathophysiology

Adrenal preclinical Cushing’s syndrome ismainly caused by adrenocortical adenoma, andis sometimes caused by AIMAH.5) In theseadenoma or hyperplasia cells, cortisol produc-tion by each cell seems to be very low. There-fore, an increase in cell number is necessarybefore excessive cortisol production occurs andcauses Cushing’s syndrome and inhibition ofACTH secretion. In contrast to these cells,large cortical cells in micronodules have potentcortisol production in PPMAD.

In primary aldosteronism, the aldosterone-producing adenoma often produces cortisol aswell as aldosterone and shows preclinicalCushing’s syndrome. In these patients, we haveto be careful because these patients cause mildadrenal failure after removal of adrenal tumor.

Patients with preclinical Cushing’s syndromeare frequently found in middle-aged womenin Japan. Total weight of adrenal glands

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(adenomas) are 10–15 g.

Diagnosis

Recently, diagnostic criteria for adrenalpreclinical Cushing’s syndrome have beenreported6) as shown in Table 1. General obesity,hypertension, and glucose intolerance are con-sidered as non-specific findings of Cushing’ssyndrome. Specific signs and symptoms ofCushing’s syndrome are not found in thissyndrome, such as central obesity, moon face,buffalo hump, purple striae, atrophic skin, andso on.

Early morning plasma cortisol levels arewithin the normal limit, while late eveninglevels are often elevated. This means abnormalcircadian rhythm. If the late evening cortisollevels are higher than 5�g/dl, preclinical

Cushing’s syndrome is strongly suggested. Uri-nary free cortisol excretion is usually between100–150�g/day. Early morning plasma ACTHlevels are often low or less than normal (lessthan 10 pg/ml). To confirm the inhibition ofACTH secretion, CRH test is recommended.If the peak plasma ACTH level remains lessthan 150% of the basal level after CRH admin-istration, ACTH secretion is thought to beinhibited. Plasma DHEA-S levels are ACTH-dependent after puberty and such levels gradu-ally decrease with age. So age-matched plasmaDHEA-S levels should be examined and theselevels are usually suppressed in these patients.In scintiscans with 131I-labeled cholesterol ofACTH-inhibited patients, asymmetrical uptakeindicates a functional adenoma, whereas sym-metrical uptake indicates bilateral hyperplasia.These data indicate autonomous secretion ofcortisol and inhibition of ACTH secretion.

Single dose (overnight) dexamethasone sup-pression test is useful to demonstrate auto-nomic secretion of cortisol. Overnight mg dexa-methasone suppression test is recommendedfor screening for preclinical Cushing’s syn-drome. If the next early morning plasma cor-tisol level is higher than 3�g/dl after 1 mgdexamethasone administration (at 11 pm pre-vious day), such a patient has a possibilityof this syndrome. Then, the overnight 8 mgdexamethasone suppression test should beexamined. If the next early morning plasmacortisol level is higher than 1�g/dl after 8 mgdexamethasone administration, the patient hasa strong possibility of this syndrome.

Treatment

Surgical criteria for this syndrome are asfollows;1. Tumor size is more than 5 cm.2. Even if the tumor size is less than 5 cm,

tumor size is increasing with time.3. Malignancy is suspected from the results of

CT, MRI, etc.4. Demonstration of autonomic secretion of

Table 1 Criteria for Diagnosis of Adrenal PreclinicalCushing’s Syndrome

1. Presence of adrenal incidentaloma2. Lack of specific clinical findings of Cushing’s syndrome3. Examination

(1) Normal early morning plasma cortisol levels*1

(2) Autonomic secretion of cortisol*2

(3) Inhibition of ACTH secretion*3

(4) Suppression of uptake on the non-tumor side inadrenocortical scintiscan

(5) Abnormal circadian rhythm(6) Low plasma DHEA-S level*4

(7) Postoperative adrenal insufficiency or attachedatrophic non-neoplastic part of the adrenal cortex

In the examination, if (1) and (2) are completed and(7) or at least one among (3)–(6) is positive, resultsof examination are considered as positive.

When 1, 2, and 3 are positive, a patient is diagnosed aspreclinical Cushing’s syndrome.

*1: Plasma cortisol levels should be determined at leasttwice. Plasma cortisol levels should be always withinnormal limit.

*2: Overnight 1 and 8mg dexamethasone suppression testScreening test (1 mg) : �3�g/dl is positiveDiagnostic test (8 mg): �1�g/dl is positive

*3: Basal plasma ACTH levels are �10pg/mlLow or no response of ACTH to CRH stimulation

*4: Age matched DHEA-S level

PRECLINICAL CUSHING’S SYNDROME


cortisol and inhibition of ACTH secretion.5. Improvement of hypertension, general obe-

sity or glucose intolerance is expected.Adenomectomy or adrenalectomy is recom-

mended when criteria are completed. Wheninhibition of ACTH secretion is severe (theplasma ACTH level is less than 10 pg/ml or noACTH response to CRH), a surgery should becareful about adrenal failure after removal ofthe tumor.

REFERENCES

1) Kloos, R.T., Gross, M.D., Francis, I.R.,Korobkin, M. and Shapiro, B.: Incidentallydiscovered adrenal masses. Endocr Rev 1995;16: 460.

2) Ross, N.S.: Epidemiology of Cushing’s syn-

drome and subclinical disease. EndocrinolMetab Clin North Am 1994; 3: 539.

3) Osella, G., Terzolo, M., Borretta, G. et al.:Endocrine evaluation of incidentally discov-ered adrenal masses (incidentalomas). J ClinEndocrinol Metab 1994; 79: 1532.

4) Reincke, M., Nieke, J., Krestin, G.P., Seager,W., Allolio, B. and Winkelmann, W.: PreclinicalCushing’s syndrome in adrenal incidenta-lomas: Comparison with adrenal Cushing’s syn-drome. J Clin Endocrinol Metab 1992; 75: 826.

5) Suda, T.: Preclinical Cushing’s syndrome andadrenocorticotropic hormone-independentbilateral adrenocortical macronodular hyper-plasia. Int Med 1997; 36: 601.

6) Nawata, H., Demura, H., Suda, T. and Taka-yanagi, R.: Preclinical Cushing’s syndrome. In:Annual report of the Ministry of Health andWelfare “Disorders of Adrenal Hormones”(Nawata, Ed.) 1996, p.223. (in Japanese)

T. SUDA



Characteristics of Multislice CTJMAJ 45(4): 175–179, 2002

Kazuhiro KATADA

Professor, Department of Radiology, Fujita Health University, School of Medicine

Key words: Multislice CT; Isotropic voxel; Volume visualization; CT scanning

widely used, however, those systems with 8 and16 rows of detectors are now to be released.The most basic 4-row MSCT detectors aredivided into 3 types (Fig. 1), although they arestructurally divided into 2 types. One is knownas the matrix type in which small detectors(cells) are arranged at equal intervals in gridformation. The other is the adaptive array type,in which detector units with increasing widthstoward both ends are arranged symmetrically.Multiple slice widths can be selected with bothtypes, by combining the number of rows ofdetectors used.

MSCT is also different from conventionalsingle slice CT in terms of the image (reconstruc-tion algorithm) calculation method it employs.2)

The helical scanning with 4-row detectors pro-vides data which are several times as large asthose of conventional single slice CT and havehigher density. These data are used to calculatea high-resolution section image of the target siteusing a technique called Z-axis multiple-pointweighed interpolation.

To obtain high image quality with multislicehelical scanning, it is important to determinethe distance moved by the patient table duringone rotation of the scanner. A concept knownas pitch (helical pitch) is usually used as anindex of the distance of table movement. The

Introduction

The multislice CT (MSCT), or multi-detector-row CT (MDCT), is a CT system equipped withmultiple rows of CT detectors to create imagesof multiple sections. This CT system has differ-ent characteristics from conventional CT sys-tems, which have only one row of CT detectors.The introduction of this advanced detector sys-tem and its combination with helical scanninghas markedly improved the performance of CTin terms of imaging range, time for examination,and image resolution. At the same time, thetime for scanning (the time required for 1 revo-lution) has been shortened to 0.5 sec. and thewidth of the slice (tomographic plane) reducedto 0.5 mm. Thus, dramatic improvements havebeen made in CT-based diagnostic techniques.1)

Since its excellent clinical effects have beendemonstrated, MSCT has become rapidly wide-spread: more than 500 systems are now in use inJapanese medical institutions. This paper out-lines the basics and characteristics of MSCT.

Basics of MSCT

The most important aspect of MSCT is thedetectors (multislice detectors). The multisliceCT systems with 2 or 4 rows of detectors are

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K. KATADA

helical pitch is determined by dividing the dis-tance of the table movement per rotation of theX-ray tube by the detector width equivalent to1 slice. In conventional helical scanning, thetable moves for a distance equal to the slicewidth during 1 rotation of the X-ray tube (thatis, pitch 1). In contrast, the pitch can be adjustedup to 6 in MSCT: the table can be moved by ahalf channel per rotation (pitch 3.5 or 4.5) or by1 channel per rotation (pitch 3). The pitch isclosely correlated with image quality and expo-sure dose. In general, image quality is improvedand exposure dose is increased as the pitch isreduced, while image quality is worsened andthe exposure dose is reduced as the pitch isincreased.3)

Characteristics of MSCT

The defining characteristic of MSCT is the

dramatic increase in the imaging range per rota-tion due to the combination of multiple rows ofdetectors with helical scanning. This allows clini-cal technicians to obtain an image for a range

15×1mm

32mm

4×0.5mm

15×1mm

16×1.25mm

20mm

5mm

1mm

5mm2.5mm 2.5mm1.5mm 1.5mm

20mm

（1）

（2）

（3）

Fig. 1 Multislice CT detectorsMatrix type (1, 2) and adaptive array type (3)

Fig. 2 Wide-range imaging (of a normal volunteer)The range from the head to thighs is covered with one scanning.

Fig. 3 Example of high quality three-dimensional imagesThree-dimensional image of the circle of Willis with an intra-venous injection of contrast medium (volume rendering tech-nique). A cerebral aneurysm with a diameter of �1mm (arrow)can be clearly identified at the origin of the superior cerebellarartery.


CHARACTERISTICS OF MULTISLICE CT

exceeding 1 meter during single breath holding(Fig. 2). At the same time, the scanning time ofMSCT can be reduced by up to one-tenth thatof single slice CT when an image with the samescanning range is required.

Another characteristic of MSCT is its excel-lent Z-axis resolution. Single slice CT coversonly a narrow range when helical scanning isperformed with a thin slice (for example, a1-mm slice). In contrast, MSCT can fully coverthe whole target organ even with a thin slicebecause it has a wider scanning range per scan,as described above. These characteristics haveenhanced the usefulness of MSCT in three-dimensional imaging diagnosis using computergraphics (Fig. 3). Since a very thin slice of0.5 mm can be used, MSCT can visualize micro-structures which could not be achieved withconventional scan techniques (Fig. 4).

When MSCT is used with thin slices of 1 or0.5 mm, resolution is equal among the direc-tions of X, Y, and Z axis of a voxel that is theminimum unit of an image. This minimum unitis called an isotropic voxel.1) The partial volume

Fig. 4 Visualization of auditory ossicles with a 0.5mm sliceThe microstructure of the middle ear including stapes (arrow) can be clearly visualized.

Fig. 5 High resolution coronal section of the abdomenwith isotropic voxelsIt clearly shows Borrmann’s type III gastric cancerand swollen lymph nodes.

effect based on slice width, which was a seriousproblem with conventional CT diagnosis, canbe avoided in images based on the isotropicvoxels. Therefore, reproducible images can beobtained, irrespective of the direction and sizeof the target structure of diagnosis. MSCT hasother advantages including reduced artifacts,


improved reliability of CT values, and refor-matted sagittal or coronal sections that can beobtained with the same axial resolution as axialsections (Fig. 5). Thus, MSCT with isotropic volu-metric data has revolutionized imaging diagnosis.

Problems with MSCT

The most significant shortcomings with MSCTare the increase in the volumetric data pro-duced by the increased use of thin slices. Theincrease in data directly influences the patientthroughput because it prolongs the time requiredfor image reconstruction4–6) and transferringand indicating data. Therefore, MSCT requiresprocessing units, network environment, and dis-play systems with higher speed capacities. Italso requires hard disks, memories, and imagestorage devices with much larger capacities. AsMSCT images have increased the number ofimages, it has become unrealistic to observethem on films. Instead, diagnosis with theimages displayed on the monitor (so-calledCRT or monitor diagnosis) has become essen-tial. Furthermore, as the use of sagittal andcoronal sections has increased, it has becomenecessary for clinicians to have a knowledge ofboth axial anatomy and longitudinal anatomy.The increased burden on radiologists who arerequired to interpret a large number of imagesis also a serious problem.7)

Future of MSCT

Although 4-row MSCT systems have juststarted to become widespread, the developmentof next-generation MSCT systems is already inprogress and it is considered certain that 8- or16-row multislice systems will be released atthe end of 2001. What is the true clinical signifi-cance of these advanced multi-row detectors?Since current 4-row systems have already pro-vided sufficient scanning range and speed, theprimary significance of the 8- or 16-row detec-tor system is to improve the Z-axis resolutionwith thin slices. It is possible that very thin

K. KATADA

slices of 0.5 or 1 mm, which are now limited dueto small coverage, will be used as a standardparameter.

Another issue of clinical significance in intro-ducing the 8- or 16-row systems is to simplifyscanning conditions. With the existing 4-rowsystems, it is necessary to select the scanningparameters on the basis of the clinical situation.However, the next-generation multislice detec-tors system will be able to employ scan param-eters that will continually ensure optimum imagequality thanks to their dramatically increasedspeed. In emergency situations at night, forexample, even those not specialized in CT canuse the system since the operator is not requiredto execute complicated parameter selection. Ini-tial images can be provided as a thick slice and,if necessary, re-processed to generate high reso-lution images for further investigation using theraw data. That is, one scanning enables bothscreening and detailed examination. This is oneof the most significant advances in the historyof CT.

Apart from the above commercially avail-able products, a CT system with multiple-rowdetectors has been developed for research pur-poses. This is an experimental system equippedwith 256-row area detectors and developedunder the project of the “High-speed Cone Beam3-dimensional X-ray CT (Energy Use Ratio-nalization) Development Committee” supportedby the New Energy and Industrial TechnologyDevelopment Organization (NEDO).8) A clini-cal study on the experimental system is sched-uled to be conducted at the end of 2001 in orderto develop a “four-dimensional scanner” thatobtains real-time three-dimensional informa-tion. It is considered promising as a prototypeof the next-generation systems.

Conclusion

The diagnostic ability of MSCT systems is farhigher than that of conventional single slice CTsystems. Such systems have been developedand are now more widespread than ever, and


CHARACTERISTICS OF MULTISLICE CT

image reconstruction in multislice helical CT.Med Phys 1998; 25(4): 550–561.

3) Tsujioka, K.: Principle of multislice CT. Jour-nal of Japanese Association of Radiology 2000;56(12): 1391–1396. (in Japanese)

4) Akabane, M.: Imaging diagnosis with multi-slice CT—Possibility and future prospect. NewMedicine 1999; 293: 53–56. (in Japanese)

5) Kadota, M., Yamashita, Y. and Takahashi, M.:Application of multi-row detector CT. ImageInformation (M) 1999; 31(20): 1117–1126. (inJapanese)

6) Kobayashi, S., Shiragami, N. and Hiramatsu,K.: Dynamic study with multiple detector rowCT. Image Information (M) 1993; 31(20): 1146–1153. (in Japanese)

7) Katada, K.: Multislice CT. Clinical Neuro-science 2000; 18(9): 1009–1012. (in Japanese)

8) Edited by Medical Welfare Equipment ResearchCenter: 1999 Results Report. High-speed cornbeam three-dimensional X-ray CT (energy userationalization). 2000. (in Japanese)

the advances have been much more rapid thanwas expected by most physicians. The present4-row systems are clinically quite useful, but onlyrepresent the earliest stage of MSCT develop-ment. After its clinical application, area detec-tor CT employing several-hundred rows ofdetectors will have the potential to replace con-ventional radiography in a number of examina-tions, and as a consequence, it is currently dif-ficult to accurately define the indications andlimitations of MSCT. All clinicians will need towatch closely the future of the diagnostic revo-lution that has been brought about by MSCT.

REFERENCES

1) Katada, K.: Half-second submillimeter real-time multi-row helical CT—CT diagnosis byaquilion. Medical Review 1999; 72: 62–70.

2) Taguchi, K. and Aradate, H.: Algorithm for

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