Br Heart J 1987;58:306-15

Review

Da Costa's syndrome or neurocirculatory asthenia

OGLESBY PAUL

From the Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

SUMMARY The syndrome variously called Da Costa's syndrome, effort syndrome, neuro-circulatory asthenia, etc has been studied for more than 100 years by many distinguished physi-cians. Originally identified in men in wartime, it has been widely recognised as a common chroniccondition in both sexes in civilian life. Although the symptoms may seem to appear after infec-tions and various physical and psychological stresses, neurocirculatory asthenia is most oftenencountered as a familial disorder that is unrelated to these factors, although they may aggravatean existing tendency. Respiratory complaints (including breathlessness, with and without effort,and smothering sensations) are almost universal, and palpitation, chest discomfort, dizziness andfaintness, and fatigue are common. The physical examination is normal. The aetiology is obscurebut patients usually have a normal life span. Reassurance and measures to improve physicalfitness are helpful.

Da Costa's syndrome or neurocirculatory astheniahas a long and honourable history in the medicalliterature and in clinical medicine. Yet it is infre-quently mentioned today. It is unlikely to have dis-appeared; it probably exists much as before but ismore often identified and labelled in psychiatricterms such as "anxiety state" or "anxiety neurosis".There is no harm in this shift in diagnostic labels aslong as the essential importance of the syndrome, itsprognosis, and treatment are properly appreciated.Such is not always the case and, as in other medicalissues, it is educational to review and summarise thepast. What has been forgotten should not necessarilyremain forgotten.For the purposes of this discussion, a broad

definition of Da Costa's syndrome that is applicableto military and civilian patients is: a disorder ofunknown origin, often familial, characterised by thepresence of one or more symptoms includingbreathlessness with and without effort, palpitation,nervousness, chest discomfort not typical of anginapectoris caused by ischaemic heart disease,fatigability, and faintness; tending to occur inattacks which may recur over years and for whichthere is no specific treatment.

Requests for reprints to Dr Oglesby Paul, Countway Library ofMedicine, Harvard Medical School, 10 Shattuck Street, Boston,MA 02115, USA.

Accepted for publication 19 May 1987

Although Jacob M Da Costa is the name mosthonoured by history in this condition, at least oneother relevant report antedated his paper in 1871.On 3 June 1863 Dr Henry Hartshorne made apresentation regarding heart disease in the UnionArmy to the College of Physicians in Philadelphia.He commented: "Among the chronic affections ofsoldiers, which are best studied in hospitals remotefrom the field, is one which does not seem to havemet, as yet, with full appreciation by medicalofficers, inspectors and pension surgeons... Theaffection to which I allude may be designated as mus-cular exhaustion of the heart."'Dr Hartshome went on to mention that Dr Alfred

Stille had delivered an address on a somewhat simi-lar disorder, referred to by him as "palpitation",before the Philadelphia County Medical Societyfour months earlier.2 Stille had noted that this pal-pitation was "a very frequent symptom among thesoldiers, occurring in perhaps every case of inter-costal neuralgia, but often, also, originating appar-ently in a state of extreme exhaustion..."Hartshorne described how in an 80 bed ward of aUnion army hospital over a seven month period themajority of the cardiac patients exhibited neitherhypertrophy nor dilatation, or palpitation "fromsympathy with irritated stomach, from nervousness,abuse of tobacco, etc", but cardiac muscular exhaus-tion. This was demonstrated by shortness of breathafter moderate exertion and a rapid pulse on slighteffort. The men appeared well and there were no

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Da Costa's syndrome or neurocirculatory asthenia

cardiac murmurs; however, sometimes the first heartsound was diminished. Although there wasimprovement with several months of rest this didnot cure most of the cases. He considered that theprocess was attributable to the stress of the militarycampaigns with "great and prolonged exertion withthe most unfavorable conditions possible-privationof rest, deficient food, bad water, and malaria."Four year later in February 1867, Dr W C

Maclean, who was Professor of Military Medicine atthe British Army Medical School, wrote a lectureentitled "Diseases of the heart in the British Army",which was published in the British Medical Jour-nal.3 His message regarding British soldiers wasdifferent from that of Hartshorne because he wascalling attention to cardiac hypertrophy anddilatation caused, he considered, by excessive exer-tion from carrying the soldier's field pack, whichamounted to over 60 pounds, and by the manner inwhich its straps constricted the circulation. Nosymptoms are described in Maclean's paper and ithardly belongs in this historical sequence started byHartshorne, although both were concerned with therole of physical exhaustion.The first major publication on the topic was enti-

tled "On irritable heart: a clinical study of a form offunctional cardiac disorder and its consequences" byDr Jacob M Da Costa, published in the January1871 issue of the American Journal of Medical Sci-ences.4 Da Costa was only one of a series of notablephysicians to be intrigued by this problem, whichover the next 70 years included some of the greatnames in internal medicine.Da Costa was born in 1833 on the Island of St

Thomas in the West Indies. He was educated inEurope and came to Philadelphia in 1849, where atthe age of 16 he entered Jefferson Medical College.He graduated three years later at 19 and went on toenrich his education with 18 months of observationin the clinics of Paris and Vienna before returning topractise in Philadelphia. Wooley reviewed his dis-tinguished career,5 which included publication in1864, when Da Costa was only aged 31, of a volumeon medical diagnosis which was so successful that itran to nine editions and was translated into German,Russian, and French. Da Costa was appointed to theposition of Chairman of Medicine at Jefferson Med-ical College, was elected President of the College ofPhysicians of Philadelphia, and was selected as oneof the original members and later president of theAssociation of American Physicians.Da Costa's role in military medicine came during

the Civil War when Philadelphia became the site ofseveral military hospitals. Da Costa was assigned toone at a suburban Philadelphia estate on Turner'sLane. Here Da Costa was exposed to a "cardiac mal-

307ady common among soldiers". He wrote a reportabout it to the War Department as early as Decem-ber 1862 and finally summarised his thoughts in the36 page article published in 1871 in the AmericanJournal of Medical Sciences.4Da Costa's clear description of this malady was

supplemented by several case histories. Althoughthe story he tells related only to soldiers, he made thepoint in the first paragraph that "Much ofwhat I amabout to say I could duplicate from the experience ofprivate practice." Therefore, this was not a phenom-enon seen solely in military surroundings. Later inthe article he confirmed this by mentioning thatsome of his patients had experienced typical symp-toms before enlisting. After commenting that he hadchosen the name of "irritable heart" for this "pecu-liar form of functional disorder", which he believedhad also occurred in British troops earlier in the cen-tury, he made the following observations.The condition often followed a period of hard ser-

vice in the field or a febrile illness with or withoutdiarrhoea; less frequently it was seen after varioussituations including battle wounds and scurvy. Themain symptoms were palpitation with a rapid pulse,with and without effort, and on occasion with slightirregularities; chest pain near the cardiac apex eithersharp and lancinating, or dull in character, comingwith and without effort; and shortness of breath,again not necessarily associated with exertion. Arange of digestive complaints was also common. Thephysical examination was described as not remark-able except for the unusually rapid pulse, a quickcardiac impulse, and sometimes apical systolic mur-murs. Treatment was prolonged and included restand digitalis preparations, at times combined withaconite or other drugs. A few patients could returnto full duty when they had completely recovered,but most had to be assigned light duty or wereretired from the service. Da Costa made the pointthat one infrequent outcome was the development ofcardiac hypertrophy, which he believed to havedeveloped in 28 of 200 cases seen. Finally, he cau-tioned that such a condition occurs with "severe orprotracted" military campaigns, and he urged ade-quate physical training for new recruits, avoidanceof forced marches, and provision for adequate con-valescence for those with acute infections beforethey returned to duty.Such were the features ofDa Costa's syndrome as

set out in 1871. It must be borne in mind that on theone hand, some of the patients indeed did have orhad had malaria, typhoid, acute gastroenteritis,scurvy, malnutrition, and physical exhaustion, andhad a reason for temporary asthenia, and Da Costaconsidered these in his description. And on the otherhand, a few others may have had organic heart dis-

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ease that was undiagnosable at the time, includingcoronary or hypertensive heart disease, myocarditis,and myocardiopathy. Rheumatic and syphilitic heartdisease would probably have been diagnosed. Dis-counting these, there was left a vivid picture of aresidual group with Da Costa's "cardiac malady"which is something else apart-an entity of uncer-tain origin, consistent clinical features, and disablingbut not life threatening consequences.Although the next major contributions in this area

came during the first world war, there were minorevidences of interest from time to time in inter-vening years. The British authorities did alter theweight and strappings of the soldiers' packs and lateraltered training drills in futile attempts to preventthe problem from occurring in the troops. (Howellhas recently written an excellent review of the Brit-ish military experience with this syndrome.6) Thecondition is said to have been encountered duringmilitary operations in South Africa and India.The first world war saw an amazing degree of con-

cern for the syndrome described by Da Costa. Someof the best medical brains in Britain were recruitedto study the problem. The reason for the mobi-lisation of all this scientific talent was the extent ofDa Costa's syndrome in the allied military forces,which became apparent during -the first months ofthe war. Alfred E Cohn wrote that as of 31 August1918, 41 699 men had been discharged from theBritish Army because of heart disease, "most ofthem probably" because of Da Costa's syndrome.7The German army seems to have had a similarexperience. Goldscheider reported to the MedicalSociety of Berlin in 1915 on the frequency in thetroops of symptoms referable to the heart due tomuscular and nervous exhaustion.8 He cited no sta-tistics. In 1916 Archives des Maladies du Coeur con-tained a review of 23 published reports of cardiacproblems in wartime, many of which resembled DaCosta's syndrome; 10 of the articles cited were Ger-man.9As early as 1915, the British Medical Research

Committee had arranged for study of "disorders ofthe soldier's heart" under the general direction ofSir James Mackenzie at University College Hospitalin London. Later, an advisory committee wasappointed including Mackenzie, Sir CliffordAllbutt, and Sir William Osler. Dr Thomas Lewiswas put in charge of the undertaking; and he, T FCotton, and F H Thiele made a brief report on theproblem in the British Medical Journal in November1915.10 Early in 1916 the Director-General of theArmy Medical Service set aside the 250 bed MountVernon Hospital in Hampstead, London, for furtherinvestigation and rehabilitative treatmnent of the con-dition; late in 1917 the activities were transferred to

Paula 700 bed hospital at Colchester in Essex. Othersmaller rehabilitation centres were opened in otherareas in 1918. British physicians assigned at the out-set to Hampstead included John Parkinson, J CMeakins, and R M Wilson.

Six physicians from the United States (Samuel ALevine, Rufus A Morrison, Dr B S Oppenheimer,Marcus A Rothschild, William St Lawrence, andFrank N Wilson) who were experienced in cardiol-ogy were assigned in the summer of 1917 to Col-chester by the Surgeon General of the United StatesArmy on the advice of Dr Alfred E Cohn. Later, in1918, the Surgeon General set aside 200 beds at theUnited States General Hospital No 9 at Lakewood,New Jersey, for the same purpose. These wereunder the direction of Dr Francis W Peabody. On 6June 1918 the hospital was made a centre for cardio-vascular disease. The medical officers there includedHarry D Clough, Cyrus C Sturgis, and Joseph TWearn.One consequence of this heightened activity was a

spate of new labels. Hartshorne had used the term"muscular exhaustion of the heart" in 1864, DaCosta had preferred "irritable heart" in 1871, SirJames Mackenzie used the label "general exhaus-tion" in 1916,11 Thomas Lewis used "effort syn-drome" in his 1919 monograph,12 and the Americanworkers preferred "neurocirculatory asthenia."'3 Avague wastebasket term, "disordered action of theheart", had also been used in the British Army, andthe equally unsatisfactory term "soldier's heart" wasused. In addition, the British army had the category"valvular disease of the heart", but in his seriesLewis reported that 161 of 277 patients with thisdesignation should be reclassified as "effort syn-drome."12The most active and the earliest interest in Da

Costa's syndrome during this period came fromBritish workers under Thomas Lewis who was thenewest bright star in the cardiac firmament and aremarkable investigator.14 Starting first at Univer-sity College Hospital in London and then at the mil-itary hospitals in Hampstead and Colchester, Lewisand his team conducted a series of studies thatresulted in more than 20 published papers.

Sir Jamnes Mackenzie who was a leading memberof this group summarised his views of the syndromeas seen in British soldiers in a report published in theBritish Medical Journal in January 1916."1 He foundthat a history of recent infections was present inmost cases, and emphasised that fatigue and exhaus-tion were always present, and breathlessness was

frequent. Depression and concern about heart dis-ease was common, as were signs of vasomotorinstability of the hands. In a 1920 article in the samejournal, he wrote: "In a careful inquiry into the ori-

Da Costa's syndrome or neurocirculatory asthenia

gin of ill health in over 2,000 soldiers I found that inthe case of about 80 per cent, the first onset of theirillness began with some complaint of an infectiousnature... In a number of cases there was no historyof infection, and the onset of the illness seemed to bedue to a variety of circumstances ... want of rest hadevidently been the provoking agent in theseinstances."'5Another early publication from the group was that

of Parkinson,'4 who described in 1916 his experi-ence with 90 "cardiac" cases passing through a casu-alty clearing station in the British ExpeditionaryForce in France in the period March 1915 to Jan-uary 1916.16 He considered that 40 of these had"soldier's heart". Thirty nine ofthem complained ofshortness of breath on exertion, 24 had precordialpain on effort (usually an ache that became sharperwith increased exertion), 16 stated they were easilyexhausted, and on auscultation nine had a short api-cal systolic murmur. After an average follow up ofseven months, only nine were back on full duty and17 were on light duty. He suggested that the "rela-tive cardiac inefficiency" must represent the effectsof previous infection, aging changes in men over 40,or a constitutional endowment of a heart "with lim-ited efficiency".A characteristic case cited was that of a 22 year old

private. "Since age of 17, palpitation and shortnessofbreath on exertion. Light bench-work. September1914, enlisted. Same symptoms on doubling or hur-rying. September 1915 to France. Palpitation, short-ness of breath, exhaustion and dull pain in fourth tosixth left spaces about nipple line, all on marching.After one month admitted. Examination: no abnor-mal physical findings. Eight months later: full dutyin France but no better."The group with Thomas Lewis reported other

observations on these soldiers. Firstly, with testexercise they became more symptomatic than con-trol subjects; they were able to do less physicallythan the controls, and their pulse rates and systolicpressures rose more than those of the presumed nor-mal soldiers.'7 Second, there was no appreciablecardiac enlargement on orthodiographic mea-surement.'8 Third, they seemed to have a slightlyreduced vital capacity.'9 Fourth, the men mightshow hyperalgesia in the precordial area.20 Fifth,although in 1916 they reported that the "cause ofbreathlessness is absence of an adequate supply ofbuffer salts in the blood,"'" a later (1919) studyshowed no clear reduction in the alkaline reserve ofthe blood.22 Sixth, symptoms were not improved bythe administration of digitalis.23 Seventh, whengiven atropine, pilocarpine, and amyl nitrite theydid not behave very differently from the controlgroup.2426 Eighth, they did not develop distinctive

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changes in the PR intervals with and after effort.27Ninth, as described by Oppenheimer andRothschild, they may have represented twopopulations-one with a positive family history anda history of symptoms before enlistment and onewithout such a background and with symptoms,particularly exhaustion and weakness, apparentlyprecipitated by an event such as an acute infection.28At Hampstead J C Meakins and R M Wilson

examined the reaction of soldiers with this syndrometo a sudden visual stimulus followed by an"unexpected discharge of a blank cartridge underthe examining couch".29 Subjects exposed to thissingular ordeal developed more rapid respiratoryand pulse rates than did the normal soldiers. (Itwould not be surprising if other physiological andpsychological effects resulted, but they were notdescribed.)

In February 1918 in the Lancet Lewis pointed tothe screening and rehabilitative value of a gradedrecreation and exercise programme conducted in thehospital.30 Of 558 men discharged over a six monthperiod in 1916 (average follow up of 11 months)approximately half could be returned to some dutycapacity. Such a successful programme soundedremarkably easy to accept, especially for men com-ing from the trenches. Cohn described how the pro-gramme included "setting up exercises, marcheswith the band; there were round games and tennis,golf and cricket; athletic competitions, lectures andpicture shows... There were theatricals, oftenarranged by the men themselves... And there wasplenty of music; in one British camp there were twobrass bands, an orchestra, a mandolin, and a banjoclub."7 Lewis proposed that a systematic course ofexercise be made available in all large military hospi-tals, a recommendation strongly endorsed by SirWilliam Osler3' and Sir James Mackenzie."Lewis summarised his experience in a 144 page

monograph published in 1919 entitled "The sol-dier's heart and the effort syndrome".'2 He con-sidered that such a rubric encompassed sixsubgroups-those with a constitutional nervous orphysical weakness, some exposed to extraordinarilyunfavourable conditions of work and sleep, thoseconvalescent from acute infectious illnesses, a fewwith as yet unrecognised infection, a small grouprecovering from gas poisoning, and another smallgroup with unrecognised heart disease. He consid-ered it not remarkable that some men developedsymptoms under wartime stresses, and pointed outthat the syndrome was also found in civilian life. Heemphasised the universality of the symptom breath-lessness (only rarely found at rest), which he consid-ered was probably related to acid-base alterations inthe blood. Fatigue, he noted, was also universal as a

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complaint and half of the patients had vague leftchest distress with or after effort, with at timeshyperaesthesia of the skin or muscles of the chestwall. Palpitation was also very frequent, and therewas occasional fainting and some giddiness. He didnot agree with Hartshorne and Maclean that thissyndrome represented heart strain. He did not findthat consumption of alcohol or tobacco, or the pres-ence of hyperthyroidism, were aetiological factors(patients with effort syndrome used less tobacco andalcohol than soldiers with gunshot wounds), nor didhe find evidence for a primary defect of the nervoussystem. He concluded that the dominant aetiologicalfactor in the clinical histories of soldiers com-plaining of the "effort syndrome" was "infection ofone kind or another". In his emphasis on the role ofinfection, he agreed with Sir James Mackenzie. Heencouraged the use of a hygienic regimen includingoutdoor activities, and of reassurance, and empha-sised that bed rest was harmful.

After the armistice in 1918, Lewis assisted theBritish Ministry of Pensions in its assessment ofcases of cardiovascular disability. An outpatientclinic was established at University College Hospitalin London, and Parkinson was placed in charge ofbeds for convalescent cases at the Ministry of Pen-sions hospital at Orpington. (Brief summaries of thecontributions of Lewis and his group during andimmediately after the first world war may be foundin the annual reports of the Medical Research Com-mittee, 1914-1915 to 1919-1920, published in Lon-don by His Majesty's Stationery Office.)In 1925 Dr Ronald T Grant, who was associated

with Lewis, published a five year follow-up of 665cases of "effort syndrome" seen at the Hampsteadand Colchester Military Heart Hospitals during theyears 1916-18 and who subsequently lived in theLondon area.32 He traced over 90% of the men.Only 15% seemed to have recovered completely butthe overall death rate in the group was not remark-able, although many of the men had developed pul-monary tuberculosis. He reasoned that incipientcardiac disease was not a factor in the syndrome.

Meanwhile, on the other side of the Atlantic inLakewood, New Jersey, at the United States ArmyGeneral Hospital No 9, a more modest wartimeinvestigative effort was initiated. Dr Francis Pea-body with Dr Clough, Dr Sturgis, Dr Wearn, andDr Tompkins reported that 65 soldiers with the"constitutionally inferior" type of the syndromeshowed an abnormal rise in systolic blood pressureor pulse rate or both in response to an intramuscularinjection of adrenaline.33 The same group withoutPeabody and Clough also administered an injectionof atropine to these soldiers and noted that therebound increase in pulse rate after an initial slowing

Paulwas greater in the patients than in the control sub-jects.34 Adams and Sturgis found little evidence of areduced vital capacity in the men,35 nor could theyconfirm the 1916 view of Lewis and his colleagues21of any abnormality in the carbon dioxide combiningcapacity of the blood and in acid-base balance.A comprehensive report from the American side

was prepared in 1919 by Dr Alfred Cohn ofRockefeller University, based both on his clinicalexperience in England at the Military Hospital atColchester and in the hospitals of the AmericanExpeditionary Force.7 He reasoned that "the heartin convalescence after acute infectious disease andthe Irritable Heart are probably not the same thing"and vigorously proposed that "this symptom com-plex is neurotic". He minimised but did not discardthe importance of constitutional inferiority, writingthat "taking constitutional predisposition intoaccount is essential, but as a complete account offailure, it appears to be inadequate." He ended hispaper with the conviction that "the disorder isessentially a neurosis, depending upon anxiety andfear; that it is removed by the disappearance of theinciting cause and that it is cured by measuresdesigned to influence the neurotic state."Neuhof, also writing in 1919 on the topic "The

Irritable Heart in General Practice," believed that"the soldier's irritable heart is no new complex, butis the same syndrome seen in civil life, intensifiedand multiplied by training and war conditions."36He believed that "some great emotion, fright, dread,shock, is usually the directly antecedent cause of theoutbreak of the cardiac symptoms. Reflex excitationfrom the gastrointestinal tract is the next most fre-quent." The fundamental process in his view was"hyperexcitation of the sympathetic nervous sys-tem".Dr Paul Dudley White of Boston had received a

letter from Dr Alfred Cohn dated 17 May 1917 sug-gesting that he become a member of the Americancontingent destined to go to England to work underThomas Lewis at Hampstead and Colchester. PaulWhite, having been trained by Lewis, was clearlyinterested in the proposal but found that he, as amember of the United States Army Medical CorpsReserve, would not be released from his commit-ments to the Massachusetts General Base HospitalNo 6. Indeed he was placed on active military ser-vice on 24 May 1917, only seven days after the dateof Cohn's letter soliciting his participation. PaulWhite had visited the Hampstead Military Hospitalon 29 August 1916 and was familiar with Britishinterest in the subject.

Paul White's first publication in this area cameafter the war in 1920 when he pointed out that, sincereturning to civilian life, he had seen in six or eight

Da Costa's syndrome or neurocirculatory asthenia

weeks 12 young patients with "effort syndrome".37This was the first scientific paper to emphasise howcommon this problem was in civilian practice, and itwas succeeded in 1934 by a more comprehensivediscussion. 13 Most of his patients were women, theirsymptoms were typical, there was no evidence oforganic heart disease, and he underscored theimportance of correct diagnosis to avoid unneces-sary invalidism. He did not support the views ofLewis and Mackenzie of an infectious or bacterialtoxic aetiology for most cases. Here at last was anopportunity to consider the syndrome away from theunusual and often highly unfavourable conditions ofwartime with their prevalence of respiratory andother infections, abnormal living conditions, uncer-tain diets, and fear of imminent death. Subsequentlyover the next 30 years he and his associates(especially Mandel E Cohen, and others includingEdwin 0 Wheeler, Henry B Craig, William P Chap-man, Stanley Cobb, Jacques Carlotti, and EleanorW Reed) produced a series of reports that exploredmany facets of this puzzling condition. They usedthe term "neurocirculatory asthenia", which hadbeen preferred by the United States investigators atthe end of the first world war.Cohen and White reported that 2-4% of the pop-

ulation had this disorder. The mean age of onset wasabout 25 years.38 The disorder affected twice asmany women as men, often occurring in successivegenerations in the same family. Unlike most earlierinvestigators they called attention to the chronicpresence of sighing respirations, the complaint ofsmothering sensations (especially in crowds), and tothe sign of a flushed face and neck; as well as to briskpatellar and Achilles deep tendon reflexes. In a 20year follow up of 173 patients, over 70% continuedto have some symptoms, but only 15% hadimportant disability. Symptoms tended to increasewith muscular effort, unusual emotion-provokingsituations, disagreeable thoughts, and exposure tocrowds, but two thirds of the patients could identifyno stimulus. Painful stimuli such as heat and a tightsphygmomanometer cuff produced abnormalresponses in subjects with neurocirculatory astheniabut not in controls. Patients could not continue aslong as control subjects with moderate musculareffort, including running on a treadmill or steppingup and down. They also showed higher pulse andrespiratory rates and blood lactate concentrationswith exercise than the controls, and pulmonary ven-tilation was higher but oxygen consumption was thesame. These observations coincided with those ofthe British workers Jones and Scarisbrick, publishedin 1946.39 Rebreathing a mixture containingincreased amounts of carbon dioxide oftenreproduced the symptoms. The symptoms of

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neurocirculatory asthenia were considered not to beidentical with those of fear alone.

In 1958, Kannel et al reviewed the resting electro-cardiogram of 203 individuals in the Framinghamstudy considered to have neurocirculatory astheniaand concluded that no electrocardiographic abnor-malities were characteristic of this syndrome,40 afinding also reported by others.

Paul White and his group concluded that thecause of the condition was unknown and that simplereassurance and observation over time were the mosteffective therapeutic measures. In their last publica-tion in 1972, Cohen and White additionally sug-gested that the syndrome might present in twoforms-a mild disorder called neurocirculatoryasthenia, and a severe illness that was actually manicdepressive disease presenting at time with cardio-vascular, respiratory, and fatigue symptoms in addi-tion to other complaints.41These extensive long term studies carried out

under both peacetime and wartime (second worldwar) conditions in civilian and military populationsgive valuable information on many aspects of theproblem. Most important of all, they drew attentionto neurocirculatory asthenia in the daily practice ofcardiology.

In the midst of these investigations by PaulWhite's laboratory, a major report on the syndromewas presented by Paul Wood in his threeGoulstonian Lectures given to the Royal College ofPhysicians in London in 1941 during the secondworld war.42 Paul Wood flatly stated that he nolonger considered that the cause and mechanismwere unknown. His was an extensive review of pub-lished reports with observations of his own. In hisstudy of 200 military cases, the symptoms in order offrequency were breathlessness (93%), palpitation(89%), fatigue (88%), sweats (80%), nervousness(80%), dizziness (78%), and left chest pain (78%).Only 24% of the subjects could hold their breathsfor 30 seconds or more, sweat was visible on thepalms in 67%, and 48% appeared nervous. He con-sidered that the left chest pain might have severalexplanations including a functional disturbance ofthe respiratory muscles, strain of the thoracic mus-cles, or "minimum trauma from the overacting heartof cardiac neurosis." He also commented on raisedresting heart rates, sweating of the palms, soles, andaxillae, and hyperventilation after forced breathing(but he did not believe that hyperventilation wasresponsible for the symptoms and signs). He consid-ered that Da Costa's syndrome should be regarded"as an emotional reactive pattern peculiar to psycho-pathic personalities and to subjects of almost anyform of psychoneurosis."

Paul Wood's conclusions included the following:

312"The symptoms and signs of Da Costa's syn-

drome more closely resemble those of emotion,especially fear, than those of effort in the normalsubject. The mechanism of somatic manifestationsdepends on central stimulation, not upon hyper-sensitivity of the peripheral autonomic 'gear'. Thiscentral stimulus is emotional, and is commonly theresult of fear. The reaction becomes linked to effortby a variety of devices, which include misinter-pretation of emotional symptoms, certain viciouscircular patterns, the growth of a conviction that theheart is to blame, consequent fear of sudden deathon exertion, conditioning and hysteria. Incapacitytends to be exaggerated consciously or subcon-sciously in order to protect the individual from fur-ther painful emotional experience."Thus Paul Wood, after wartime experience with

the condition, came down squarely on the side ofviewing Da Costa's syndrome as a manifestation ofemotion, more in keeping with the view of Cohnthan that of Mackenzie or Lewis, and unlike that ofWhite and Cohen, who considered that the issue wasdecidedly more complex.

It was doubtless in part because of Paul Wood'sinfluential views, well spread over three issues of theBritish Medical Journal in 1941, that during the sec-ond world war there was a diminished interest in DaCosta's syndrome as a medical entity. Many of thecases seem to have been treated by psychiatrists andended up with various diagnostic labels. In the thirdedition of his textbook on heart disease, published in1968, Paul Wood restated his views in accord withthis impression:

"It should be understood that there is no essentialdifference between 'effort syndrome' and 'cardiacneurosis', they are merely clothed differently, theformer in battle dress, and latter in nylon. In civillife the condition accounts for 10 to 15 per cent of allcases referred to cardiovascular clinics; it is commonin children, and occurs more often in women than inmen, the ratio being 3:2. It has a preference for theemotional races, especially the Jews and Italians. Inthe first world war there were some 60,000 'effortsyndrome' casualties in the British forces; in the sec-ond a more enlighted view was taken, the majority ofthese cases receiving appropriate psychiatric labelsand management."43

Friedberg, in the third edition of his text Diseasesof the Heart, published in 1966, also expressed apsychiatrically oriented view when he wrote: "Theunderlying cause appears to be a fundamental egoinsecurity arising from psychological problemswhich began in infancy and childhood".44 A morerecent (1974) review by Caranasos expresses a simi-lar sentiment.45The past few years have seen two further lines of

Paulexploration. The first of these has been the sug-gestion by some that there is an overlap betweenneurocirculatory asthenia and mitral valve prolapse,and that both can be considered within a singlerubric.

Jeresaty wrote in 1979 that "many of the patientspreviously described as suffering from Da Costa'ssyndrome, soldier's heart, the effort syndrome, andneurocirculatory asthenia would now be classifiedunder the heading of mitral valve prolapse syn-drome".46 Barlow and Pocock stated in 1984: "Weare also aware that some patients diagnosed by us asprimary mitral valve prolapse syndrome would beclassified by others as neurocirculatory asthenia, DaCosta's syndrome, non-specific T-wave changes,atypical chest pain syndrome, so-called 'syndromeX' or similar conditions".47 It is important that Bar-low and Pocock spoke only of "some patients".Wooley noted in 1985 and also earlier how "Asknowledge and technology progressed, the pathwayfrom neurocirculatory asthenia would eventuallylead to anxiety neuroses of World War II, systolicclick and late systolic murmur syndrome of the1960's, and the mitral valve prolapse syndrome,panic disorders, and autonomic dysfunction states ofthe 1970's and 1980's".48The fact that the disorders referred to all share

uncertain aetiology, vague symptoms, no means ofspecific identification by laboratory means, and areusually unresponsive to conventional treatmentshould not in itself justify creating a new umbrellalabel. Because both mitral valve prolapse and neuro-circulatory asthenia are common some individualsare likely to show evidence of both conditions.

It is important to emphasise, as have nearly all ofthose physicians who studied the problem carefully,that all patients with neurocirculatory asthenia com-plain of undue shortness of breath on effort andoften at rest, approximately 90% have palpitationand fatigue, and approximately 50-75% report chestpain. This is not what has usually been reportedwith the mitral valve prolapse syndrome. It isapparent that most young patients with mitral valveprolapse syndrome have no symptoms at all if thecondition is detected on a screening examination;and even among those seen in the usual clinic (office)setting, which concentrates those patients withsymptoms, symptoms are much less common than inneurocirculatory asthenia. Jeresaty reported chestpain in 61%, fatigue in 42%, and dyspnoea in only38% of 100 cases of mitral valve prolapse.46 Barlowet al in their original 1968 description of 63 patientswith systolic murmurs and in some cases non-ejection clicks, also described tiredness, palpitation,breathlessness, or chest pain in only 39 (62%).49Leatham and Brigden wrote firmly in 1980 in an

Da Costa's syndrome or neurocirculatory asthenia 313article entitled "Mild Mitral Regurgitation and theMitral Prolapse Fiasco" that "isolated disease of themitral valve causing mild or moderate reflux seldomcauses symptoms other than those of iatrogenic anx-iety."50 Leor and Markiewicz from the RambamMedical Center in Haifa, Israel, used auscultationand echocardiography to study 42 young soldierswith neurocirculatory asthenia; they concluded that"mitral prolapse and neurocirculatory asthenia donot appear to be related".51 Silverman etal studied68 patients seen in private practice, 57 ofwhom werewomen, in whom mitral valve prolapse was diag-nosed by echocardiography.52 While they concludedthat the symptoms of neurocirculatory asthenia weremore common in patients with mitral valve prolapsethan in an age and sex matched control population,only 34 of the 68 complained of dyspnoea (as did 19of the controls) and fatigue. Symptoms related toeffort were not mentioned. Retchin et al investigated274 outpatients and suggested that "symptoms anddysfunction are not related to the presence of mitralvalve prolapse by echocardiography".53 Devereuxet al in another large study concluded that "non-anginal chest pain, dyspnoea, panic attacks and elec-trocardiographic abnormalities have appeared to beassociated with mitral valve prolapse because ofascertainment bias and an erroneous classification ofdifferences between men and women as being due tomitral valve prolapse".54

It seems best to keep neurocirculatory astheniaand mitral valve prolapse as separate categories forthe time being because they do not have sufficientsimilarities to justify a single label. This does notmean that a few individuals do not demonstrate evi-dence of both conditions. The hyperkinetic heartsyndrome also appears to be different from neuro-circulatory asthenia and should also be considered asa separate entity." 16The second line of investigation has been the

treatment of neurocirculatory asthenia with j block-ing agents. Here, much as in the mitral valve pro-lapse story, there has been a modest amount ofsmoke but not much fire. Caranasos in 1974 sum-marised the situation as follows: "Recently pro-pranolol has been found effective in diminishing oreven abolishing the cardiovascular signs and symp-toms of 'NCA', but the psychic symptoms areunaffected".45 Rimon et al in an unimpressive,uncontrolled study published in 1979 in the IsraelAnnals of Psychiatry, listed many rion-specificsymptoms such as depression, palpitation, difficultyin falling asleep, tension headache, etc said to havebeen improved in 36 patients with neurocirculatoryasthenia as result of treatment with propranolol.57No conclusions are justified from this evidence.

In 1974 Wolf et al of Hadassah University Hospi-

tal in Jerusalem treated five men and five womenwith neurocirculatory asthenia with intravenouspropranolol. In all of them there was improvementin ST-T abnormalities in the resting electro-cardiograms.58 Here again, no definite conclusionscan be drawn from such observations. Indeed, thewhole area of the treatment of disorders associatedwith anxiety with ,B blocking drugs appears contro-versial.59Da Costa's syndrome or neurocirculatory asthenia

has been a common condition in the experience ofmany seasoned clinicians. Past studies have shownthat it has often had a familial background, hasoccurred in both civilian and military life, andespecially in women, has had certain identifiablesymptoms, no specific signs, and few demonstrablephysiological and psychological abnormalities.There has been no, or a poor, therapeutic responseto rest, and no convincing evidence of benefit fromdiet, surgery (adrenal gland denervation was prac-tised by Crile in the 1930s6 61), or drugs. A pro-gramme of reassurance, exercise, and physicalfitness has been of value.

It is important to be able to recognise the condi-tion irrespective of the label used. The diagnosis isusually not difficult for an interested reasonablyintelligent physician. Be alert for the youngerpatient with unexplained shortness of breath, easyfatigue, and a history of palpitation and atypicalchest pain, who sighs frequently during the courseof the conversation. All too many patients with thissyndrome, mainly women, are still mistakenlylabelled as having organic heart disease includingangina pectoris, and this leads to the additionalproblem of an unnecessary cardiac neurosis. (Not allpatients with neurocirculatory asthenia have acardiac neurosis and not all patients with a cardiacneurosis have neurocirculatory asthenia.) It is essen-tial to be able to reassure the patient withneurocirculatory asthenia, to understand that thecondition may be life long with remissions andexacerbations, and to appreciate that it may to someextent limit physically strenuous effort. Finally, itdoes not appear profitable at this time to attempt tocombine neurocirculatory asthenia and mitral valveprolapse within a single diagnostic category.

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