angina of effort - postgraduate medical...

ANGINA" OF EFFORTBY R. EWING RODGERS, M.D., M.R.C.P.

Chief Assistant, Cardiac Department, Royal Free Hospital; Honorary Physician, BolingbrokeHospital; Consulting Physician, Acton Hospital

Angina of effort was first described byHeberden in 1768 under the title of " Angina,Pectoris." The typical form is a very commonsyndrome, the diagnosis of which is obvious'to the observer with previous experience ofthe complaint. There are many atypical formswhich require much closer consideration todistinguish them from other conditions charac-terized by chest pain.

Chest pain is the cardinal feature in anginaof effort; the pain is induced by exertion,for example, by walking, and is quicklyrelieved if the patient stands still. Carefulconsideration must be given to a detailedhistory with special reference to the pain. Itis on the history and the response to treatmentthat the diagnosis rests rather than on theinvestigations.The pain is classically severe, but may be

any grade from an ache to an agonizing pain.It is often described as a sense of constrictionaround the lower or middle chest, " like aniron band " or " like being gripped in a vice."The pain is usually substernal in origin, or alittle higher up, and typically radiates to theleft arm, running down the inner side, some-times as far as the ulnar border of the handand the ring and little fingers. However, itmay radiate to the right arm or to the back,when it is usually th. right subscapular regionwhich is affected. It radiates sometimes tothe angle of the jaw, and rarely to the abdomen.In a few cases it remains fixed in the substernalregion without radiating at all.The pain lasts from a few seconds to thirty

minutes, but rarely more than a few minutesunless the movement producing it is continued.It lasts longest when the attacks are producedat rest, which occurs in the later stages of the

disease. As soon as the walking or othermovement is stopped the pain begins to passoff, only to be brought on again if the sameaction is carried out. The patient may noticehis pain coming on at approximately the samepart of a hill which he climbs each day, or hemav notice that the same movement alwayscauses it. The pain may be brought on byexcitement, anger, or other severe emotion,but these are never the only factors.A heavy meal may bring on the pain,

especially when followed by exercise. Somepatients notice exposure to cold brings on anattack, and heavy smoking has been suggestedas a cause. None of these, however, are foundalone without muscular effort as an accompany-ing factor, and if there is no pain on effort, thediagnosis should be reconsidered.The pain usually stops the patient as he

walks or carries out some energetic movement.He stands, pale and anxious, but withoutshortness of breath, and slowly his pain passesoff. There are few accompanying symptoms,and often no accompanying signs. Theheart is unaffected clinically, and the pulserate and blood pressure little altered.Angina of effort is much commoner in

males, especially in those over forty, but canoccur at almost any age. When it occurs inyoung people it may be due to rheumaticheart disease with aortic regurgitation. Thiscauses a poor blood supply to the coronariesand hence angina. This has been the view inthe past, but recently American observers havedescribed many cases in young soldiers whoare overweight and subjected to heavy strain.Angina is much commoner in the profes-

sional classes and in brain workers leading asedentary life. The white race is more prone

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POST-GRADUATE MEDICAL JOURNAL

than the coloured races, who rarely suffer fromit. Dock shows an interesting anatomicalpossibility as a background for these aetio-logical influences. He states that the coronaryarteries of males are thicker in their intimathan in females, and that this thickening ismarkedly found in the more susceptible raceswho appear to live on a diet relatively rich incholesterol. As angina is commonly associatedwith coronary disease and coronary insuffi-ciency, it may well be that the diet of civiliza-tion is a strong predisposing factor and thatthe male, by reason of his coronary intima,is a more likely subject for it.Angina is becoming an increasingly com-

mon disease, probably as the result of thestress and strain of modern existence, and inassociation with the increased prevalence ofarterial disease and early arterial degeneration.It is invariably caused by coronary insuffi-ciency, this in turn arising from atheroma,hypertension or other cardiovascular disease.The commonly accepted theory of the causeof the pain is that coronary insufficiencyproduces anoxaemia of the cardiac muscle,so giving cardiac pain, although the exactmechanism is in some doubt. The coronaryarteries are nearly always abnormal in casescoming to post mortem.

Syphilis predisposes to angina through itsaction on the aorta and the aortic valve, caus-ing an adverse effect on the blood flow to thecoronaries. Anaemias, especially perniciousanaemia, cause anoxaemia sufficient to produceangina when ordinary work is being done. Assoon as the anaemia is treated the anginalattacks disappear although the electrocardio-graphic changes, according to Hunter, may bepermanent. Thyrotoxicosis, by unusualdemands on a toxic heart muscle, can producetypical pain, but the angina clears up if thethyrotoxicosis is treated. Other infectionsinvolving fever and toxaemia increase theheart's work while undermining its efficiency,and may produce angina in a susceptibleperson. Other conditions which play a partare obesity, diabetes, gout, myxoedema, vita-min B deficiency, and possibly heavy smoking.Angina was found in 43 out of x,56o cases of

pernicious anaemia by Willis and Griffin, butcertain differences were noticed. The painwas seldom the presenting symptoms, and

when present, remained relatively fixled anddid not radiate as in angina of effort. Manywriters have denied that anaemia can giveangina by itself, but post mortems on anaemiaswith angina, do not always disclose coronaryarterial disease. Out of 34 cases of mixedanaemias described by Hunter, 8 had angina,and successful treatment of the anaemia curedthe pain in all. This is the usual finding, andserves to distinguish angina of effort fromangina secondary to anaemia.

Similarly, angina arises in thyrotoxicosis,but tends to occur only in the early stages ofthe disease, and again tends to be more local-ized in site, and responds dramatically toeffective treatment. This forms the basis forthe suggested form of treatment by surgery,which will be discussed later.

Diabetes mellitus predisposes to angina ofeffort because of the relative frequency ofatheroma and hypertension. Treatment ofthe diabetes tends to improve the angina, butthe arterial changes are largely irreversible,and therefore the angina cannot be effectivelyaltered, even with control- of the diabetes.Gout also causes arterial disease with resultingangina through the consequent coronary in-sufficiency. Any other disease leading to wide-spread arterial damage will work similarlythrough coronary disease. Examples of theseare Buerger's disease, chronic lead poisoning,and Pagzt's disease.

Paroxysmal auricular tachycardia may ini-tiate or increase attacks of angina, but auricu-lar fibrillation and angina rarely appear to-gether, and seem to be antagonistic.

Excess of smoking has been blamed bymany for angina of effort, and appears to playsome part in its causation. It has been shownexperimentally to constrict the coronaryarteries, but how often this occurs in thehuman being is open to some doubt. Patientsoften state that their attacks are less severe andfrequent when their smoking is curtailed.

Friedman has described an interesting typeof angina associated with abnormal sensitivityof the carotid sinus. In this syndrome atypical anginal pain is experienced on suddenmovements of the head, whether associatedwith other actions or not. The case describedfelt faint and had a fall of blood pressure, andsyncope as a late effect, these symptoms being

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reproduced by experimental massage of thecarotid sinus.Another cause of angina is hypoglycaemia

in susceptible subjects with labile blood sugarlevels and sensitivity to changes. In thesepeople, starvation followed by exercise, notonly produced faintness, but also an anginaindistinguishable from ordinary angina ofeffort.The degree of disease underlying the

symptom angina of effort may be very variable,some patients having a much greater sensitivityto pain than others. Thus one will experiencefrequent severe pain and limit his activitiesearly in the course of the disease, while a lesssensitive subject will persist with his muscularefforts as he experiences little or no pain.The course of the disease is variable, but

the attacks tend to get more frequent and comeon with less and less effort as time goes on.The patient may die in his first attack of painor live for thirty or forty years after it. Com-monly up to ten years will be the expectancyof life, depending largely on how the patientorders his life.The course of the disease cannot be esti-

mated by the degree or frequency of the painunless the symptoms ate progressive, as thepatient suffering the minimum of pain, andhaving a short history, may have the maximumunderlying disease, and may drop dead in anearly mild attack. The prognosis is, therefore,a difficult one, and the wise physician isguarded in his outlook, being guided by thesigns of underlying disease if present, and theprogress of the patient, and his ability to livea restricted life with advice and treatment.The prognosis is better in the nervous orsensitive patient, as he will be more likely tolive within the capabilities of his heart, andwill stop muscular efforts before over-exextinghimself. There is always the possibility ofsome complication such as coronary thrombosisoccurring, but on the other hand, there isalso the possibility that anastomotic vesselswill bring collateral circulation into being,and so increase the coronary flow and causethe angina to disappear or lessen. Death of anarea of heart muscle may cause the pain tocease-this occurs as the result of a coronarythrombosis.The prognosis is also determined by the

temperament and wishes of the patient. Hemay desire to live a shorter but more activelife on one hand, risking curtailment for a moreenjoyable or profitable existence.Angina which arises at rest is an adverse

factor in the prognosis. This occurs on lyingdown and is usually seen in patients who havegot frequent anginal attacks with the minimumof effort. Relief from the pain is gained onsitting or standing up, the cause of the painwhile lying down being due to the increasedwork thei heart has to do in the prone position,and to the lower blood pressure, with conse-quent poorer coronary circulation. Anotherfactor, in the prone position, is the rise of theabdominal contents with consequent pressureon the heart.

Rest and adequate treatment can influencethe course of the disease considerably, butthere is some dissension of opinion as towhether a period of complete rest is beneficialor not. Most observers advise a period ofcomplete rest, when the symptoms firstmanifest themselves, in the hope that thecoronary circulation may recover sufficientlyto allow of relatively normal activities.The diagnosis of angina of effort rests

almost entirely on a close consideration of thehistory and the progress of the case. There areno typical concomitant signs, although theheart is usually enlarged and various irregu-larities of rate or rhythm may be present.Frequently, atheroma of the arteries may bedetected in the peripheral or retinal vessels.The electrocardiograph shows no typical

changes, but certain changes occur relatively.frequently and may arise when the patientexercises enough to induce an attack of angina,or when he is subjected to an atmosphere withan artificially reduced oxygen content. Typi-cally one or more of the T waves in the limbleads is inverted during the attack, if not inbetween attacks, and the R.T. segment isoften altered in its take off. It can also beshown that the electrocardiograph changes donot occur with the same amount of exercise ifa suitable drug such as one of the nitrites isgiven beforehand.The differential diagnosis is often very

difficult without a clear history and needs aperiod of observation. It involves a considera-tion of other forms of chest pain. The most

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difficult conditions to distinguish are the so-called pseudo anginas.'associated with neuro-circulatory asthenia, effort syndrome, or thetype found in females nearing the menopause.In all theste latter, there is a cardiac neurosis,a fixation of ideas on the heart and its functiors,and a pain experienced, irregularly, on varyingdegrees of effort, and on occasions withoutexercise. The pain is almost invariably fixedand localized to the apical area where thepatient imagines her heart to be. It is relievedequally by drugs other than nitrites, and isopen in some degree to improvement orotherwise by suggestion. It is usually accom-panied by many other symptoms, chieflypalpitations, dyspnoea, faintness, and a feelingof ill-health. These conditions have nophysical signs other than a fast pulse rate and apoor general physique. There is a goodresponse to sedatives, rather than to nitrites.Angina of effort is to be distinguished from

chest pain due to congestive heart failure orother cardiac disease. These latter pains are allrelatively fixed and more constant and longerin duration, and respond to different treat-ment. The pain of coronary thrombosis isrelatively easy to distinguish as it is moresevere and prolonged, and more fixed to onesite, and is usually accompanied by loweredblood pressure and some symptoms of shockand collapse. It may also radiate through tothe back or upwards to the jaws in coronarythrombosis, but it nearly always begins atrest or after a heavy meal. It does not respondwell to nitrites. Pain due to ectopic tachy-cardia has already been mentioned as a causeof similar pain, although again the response isto different treatment. In a series of 77 casesof angina of effort described by Harrison,none had sharply localized pain, but on theother hand, only 50 per cent. of them origi-nated in the substernal region.

Other causes of chest pain have to bedistinguished from angina. Dyspepsia is sooften associated or confused with it, thatcareful consideration must be given to any caseof pain in middle aged people which does nothave a definite intestinal origin. Thus cardio-spasm, or spasm of the oesophagus, mayclosely simulate angina in type of pain anddistribution, but it is not produced by effort orrelieved by rest. Radiological investigations

of the intestinal tract should distinguish themif there is difficulty with the history, andresponse to treatment is also helpful. Painoriginating in the stomach may simulate trueangina in its radiation and intensity, but it isusually relieved by alkalis and has relation tofood rather than to exercise. Stimulation ofthe stomach may cause constriction of thecoronary arteries and true angina, in thosealready liable to attacks, and sometimes acombination of conditions is present. Pyloro-spasm, aerophagy, herniation of the stomachand ' cascade stomach' are all gastric con-ditions which may give rise to difficulties indifferential diagnosis.

Cholecystitis or other forms of gall bladderdisease may initiate attacks of angina reflexly,and this has to be distinguished from radiationof gall bladder pain alone. Sometimes anginaof effort is improved or temporarily 'cured'by cholecystectomy. On the other hand,-spasm of the muscle of Oddi after cholecystec-tomy may mimic angina closely (Clark).Many other conditions such as tabes, herpes

zoster, aneurysm or osteoarthritis of spine maylead to initial confusion, but the history usuallydifferentiates them relatively easily, and in-vestigations make the 'diagnosis definite. Car-cinoma of the bronchus' must always beconsidered as a cause, and a radiogram of thechest taken.

It only remains to consider the treatment ofangina, which resolves itself largely into anorganization of life and habits so as to preventpain, and the use of one or two well-trieddrugs. There is little dissension in the former,but fresh drugs are constantly being tried in aneffort to find one which will meet all the re-quirements. The attack of angina itself. brooksof no delay in treatment and a sufferer quicklyestablishes his own measures for temporaryrelief. He learns that a certain amount ofexertion will bring on a spasm of pain, andthat standing still will enable the pain to passoff. Soon he knows just how much effort heis capable of taking without initiating furtherattacks, or at any rate, without having frequentattacks, for so many imponderables affect theonset that he will probably have some attacksin spite of all efforts to prevent them. A periodof complete rest in the early stages of anginapectoris may well keep the condition at bay

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for a considerable time, as collateral channelsof coronary circulation may then be opened up.The patient will have to lessen his general

activities, and avoid precipitating factors.This means he will have to avoid strenuousexercise, large meals, or exercise soon aftermeals, undue exposure to cold, or exposure tocold following a meal, and excitement or ex-cessive emotion of any description.' Excessivesmoking should also be avoided and only aminimum allowed, as patients have found thatsmoking in any amount does tend to increasethe frequency of attacks. Certain experi-mental evidence is in favour of this, as nicotineis shown' 'to cause some constriction of thecoronary vessels.A holiday away from all the usual energetic

occupations may well be beneficial in the earlystages of the condition, and a completephysical and mental relaxation may benefit theunderlying condition by enabling the heart tobecome adjusted to its altered arterial supply.Any underlying or associated disease capable

of treatment such as anaemia or thyrotoxicosisshould be treated energetically, and this mayin turn benefit the angina enormously.

After consideration of general measures,drugs for the attack, and drugs for preventionof the attack, need to be considered. Littleadvance has been made in this treatment ex-cept in a negative direction, as one drug afteranother has been tried and found of little use.Stokes states 'Glyceryl trinitrite has had noequal in the relief and prevention of theanginal attack,' and with this statement fewobservers would quarrel. The nitrites have anestablished place by themselves in the treat-ment of angina. Evans and Hoyle comparedthe effects of a wide range of dtugs in theprevention of attacks, and in the reduction ofthe pain, and showed that none could be rt liedon when compared with controls or the use ofplacebos.

Several nitrites have been tried, rangingfrom the rapidly acting amyl nitrite to erythrolnitrate, but the intermediate glyceryl trinitrinihas been found best for common use. Amylnitrite (m, 1-3) in capsules works very quickly,but the effects pass off equally quickly. It isput up in small ampoules which are crushedand the contents sniffed. The result is vaso-dilatation which also affects the coronaries,

but produces unpleasant banging in the headand other side effects. The ampoules areexpensive when used frequently.

Glyceryl trinitrate is used in tablets ofgr. i/ioo, gr. I/I20, or gr. 1/200. The tabletsshould not be allowed to get old and hard, andshould be quickly absorbed from under thetongue. It has less severe side effects thanamyl nitrite, is longer lasting, cheaper andeasier to carry. A tablet can be taken beforeany effort which has to be carried out, andwhich has previously produced attacks ofangina. One or two daily may be takenprophylactically or reserved for special efforts.-No bad effects seem to arise from using themhabitually and in frequently repeated doses.

Erythrol nitrate (gr. -X) is a slower actingand longer lasting drug of the nitrite series,taken in tablet form by the mouth. It lastsseveral hours and takes about half-an-hour toact.

All other nitrites are of little use clinically,and in practice, glyceryl trinitrate is invariablythe drug of choice. If it is not available in anemergency, a few ounces of whisky or brandywill soon ease the pain, but rest will usually dothis equally well, and there is always the riskof chronic alcoholism if the drug is used andfound to work. Inhalation of ether used to beused, but has been given up owing to its slowaction and its side effects. Other sedativedrugs are useless for the pain, but help tocontrol the excitement or nervous elementwhich may help to set off an attack. It is thuscustomary to take a small dose of pheno-barbiton , for example gr. fs. b.d.The next most useful drugs, a group of

purine derivatives, act by dilating the coronaryarteries over a period, and increasing the bloodflow to the heart, and thus lessening the chanceof anginal attacks. Not all, observers haveagreed on the extent of their efficiency, butthey appear to act symptomatically in manypatients, and the small group of hypertensiveangina patients do particularly well on thesedrugs. Theobromine and thzophylline, andtheir derivatives are the chief members of thisgroup. The most commonly used in thiscountry are cardophyllin, aminophyllin, anddiuretin, and they are prescribed in tabletform over a long period. Unpleasant sideeffects are seldom experienced, but flushing

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and nausea have been described. Steinbergand Jensen gave theophylline a clinical trialand came to the conclusion it had little effecton the acute attacks, but it remains as a factorin treatment over a long term period.Another drug to be tried widely is nicotinic

acid. Stokes conducted a clinical trial of thisin comparison with nicotinamide, glyceryltrinitrini and placebos. His conclusions werethat there was no appreciable effect with anyexcept glyceryl trinitrini, and unpleasant sideeffects such as flushing, fainting and drop inblood pressure, occurred with nicotinic acid. Ifthe nicotinic acid was used in large dosage itdid, in some cases, prevent the irregularities ofthe R.T. segment and, the T waves occurring,which otherwise arose on exercise or artificiallyproduced anoxaemia. It did not, however,keep the electrocardiograph normal as long aswith the nitrites, and the side effects weremuch more unpleasant.Gray investigated the use of papaverine

hydrochloride and found that large irtra-venous dosage (200 mgm.) had to be given for alimited temporary effect to allow exercise to betaken. By mouth there was no appreciableresult and unpleasant side effects arose withthe intravenous dosage.

Recently, sex hormones have had a vogue,and there is still conflicting evidence on theirefficacy. Strong and Wallace report 20 casesof angina due to arteriosclerosis, six of whichthey claim showed marked improvement, i ionly moderate, and the rest, none. They hadtreatment with 25 mgm. of testosterone pro-pionate daily by injection for four to five daysin the males and 5 mgm. of oestradiol daily inthe females. Their conclusions were drawnfrom the amount of glyceryl trinitrininecessary, and the frequency of attacks withhormone treatment compared with nitritesalone. Various tissue extracts have also beentried, but found of little use.Many other drugs have been tried, but none

have survived to become of use in the patientwith angina.

Surgical measures have been tried for sometime and are still being developed. There areDone of proven worth as yet, but increasing useis being made of some of thr operations.

Surgery offers three modes of attack on thepioblem. First thyroidectomy has been tried

in an effort to reduce the basal metabolic rate,and the blood requirements of the heattmuscle, and so allow the diseased coronaries tosuffice for their work. It is a severe operationand apart from the initial risk and the question-able result on the heart, the myxoedema re-sulting may produce still further arterialdisease.

Recently thiouracil has been given in anattempt to lower the basal metabolic rate, andso directly relieve the pain. As it has to begiven over a long period, to a person with anormal basal metabolic rate, to produce a fall,the risks of toxic effects are greater, andtherefore its use is only permissible in severeanginas in whom other measures have failed,or where there are contra-indications to othermethods. If thiouracil is given, the dosageshould be small, in the region of ioo/mgm.daily, and frequent blood counts should beundertaken to preclude leucopenia andagranulocytosis.The second approach is to give a better

blood supply to the heart by anastomosingother tissues, to bring in a collateral bloodsupply. Thus cardio-omentopexy aimed atbringing blood from the abdomen to the heartmuscle, and Beck joined the subpectoralmuscle to the heart with a similar idea. Neitherof these operations have been widely practisedand are big undertakings. Further evidenceof their success will have to be produced beforethey can be advised.The third surgical measure is to attempt to

relieve pain, and possibly increase the coronarycirculation, by cutting out the sympatheticnerve supply. This has been practised for 30years by means of different techniques andapproaches, and various operations have beendevised for sectioning different parts of thesympathetic system thought to control theheart and coronary flow. Recently a bigstimulus has been received by the work ofSmethwick and others in America using ex-tensive operations involving thoracic andabdominal approaches. The operations havebeen devised and used primarily for the treat-ment of hypertension, but sufferers fromsever angina who can be judged to have goodenough general health to stand up to such asevere operation, have also benefited from itin carefully chosen cases. This seems a

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promising field of surgical therapy in the futurefor relief of pain, but apart from the surgicalmortality, there remains the danger of ' pain-less coronary thrombosis ' or other cardiaccomplications if the warning signal of angina isremoved. Many patients will carry out taskstoo great for their deficient coronary circula-tion, and without any warning of danger, willincur severe cardiac complications.

Finally, a word may be said for the minorsurgical manoeuvres. The injection of novo-caine into the pectoral muscles may, in somenot clearly understood way, prevent theattacks of angina for a considerable time, andthe injection of local anaesthetic or alcoholinto the dorsal invertebral roots often has amarked effect in the reduction of pain. Insuccessful cases the anginal attacks ceasealtogether, but the danger remains, as insympathectomy, that the patient will do morethan his cardiac condition can support.

These injections are a much safer method oftherapy for the intractable case than the major

surgical manoeuvres. They should be tried incases experiencing frequent severe attacks, whoare not given a comfortable existence bymedical treatment, and whose general healthwill standsthe necessary amount of interference.It is also preferable to choose cases who willfollow a regime of after treatment, and will becontent to live a restricted life within thebounds of their hearts' capabilities.

This paper cannot be concluded withoutrecording how many of its ideas have beengained from the teaching of Dr. T. JennerHoskin.

REFERENCES

CLARK, W. E. (1945), .7.A.M.A., 128, 352-356.DOCK, W. (I946),J.A.M.A., Vol. 13i, No. II, July 13, p. 875.EVANS, W. and HOYLE, C. (iy), Quart J. Med., ii, 311.FRIEDMAN, M. (I945), Amer. Heart J., 29, 37-43, Jan.GRAY, W. (i94g), New England J. Med., 232, 389-394, April.HARRISON, T. R. (I944), Amer. J. Med. Sci., 207, pp. 56i, 587.SMITHWICK, R. H. (i944), Arch. Surg., 49, i80-I93, Sept.STEINBERG, F., and JENSEN, J. (I945), J. Lab. and Clin. Med.,

30, 769-763, Sept.STOKES, W. (i944), Brit. Heart J., 6, I157-i60, July.STRONG, G. F., and WALLACE, A. W. (i944), Canad. M.A.J.,

50, 30-33, Jan.WILLIS, F. A., and GRIFFIN, H. Z. (1927), Amer. 7. Med. Sci.,

174, 30.

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