422

LONE PULMONARY HYPERTENSIONBy D. S. SHORT, M.D., M.R.C.P.*

The Department of Cardiology and the Institute of Clinical Research and Experimental Medicine, The Middlesex Hospital,and the Cardiac Department, The London Hospital

Lone (or primary), pulmonary hypertension(P.H.T.) may be defined as a condition of highpressure in the pulmonary artery associated withright ventricular hypertrophy for which no causecan be found outside the pulmonary vessels. Thediagnosis is one which is made by exclusion ofother diseases which are known to be potential orpredisposing causes of P.H.T. The most importantof these are chronic lung disease, mitral stenosis andcongenital heart disease (Bedford, 195I). Lessfrequent causes are recurrent pulmonary em-bolism and pulmonary arteritis.The forms of lung disease most frequently

associated with P.H.T. are emphysema and pneu-moconiosis. Fibroid tuberculosis, cystic disease,sarcoidosis, secondary carcinomatosis and primaryhaemosiderosis are sometimes responsible. Kypho-scoliosis is another rare cause. The most im-portant varieties of congenital heart disease arethose which permit a left to right shunt, notablyatrial septal defect, ventricular septal defect andpatent ductus arteriosus. Repeated pulmonaryembolism secondary to thrombosis in the systemicveins is an important and not very rare cause ofP.H.T.; so also, in Egypt, is bilharzial pulmonaryendarteritis; but rheumatic and syphilitic pul-monary arteritis are very uncommon.Under the diagnosis of primary pulmonary

arteriosclerosis, occasional cases of Lone P.H.T.have been reported since the middle of the lastcentury, but by I935 Brenner could find reports ofonly 15 pure and well authenticated cases. Duringthe past 20 years, and particularly since the intro-duction of cardiac catheterization, many morecases have been described. The disease is never-theless a rare one and there are still less than 0ooadequately reported cases with necropsy controlin the world's literature. Dr. William Evans andDr. Evan Bedford are about to publish a consider-able series of cases which were carefully studiedboth during life and at necropsy. Through theircourtesy the present author has had the oppor-tunity of examining several of the patients during

* Holding a Leverhulme Scholarship.

life, as well as all the case records and post-mortem material.

AetiologySymptoms usually make their appearance in the

third or fourth decade, less commonly in child-hood, though cases have been reported as youngas six months and as old as 74 years. The sexincidence is noteworthy, for females outnumbermales by approximately two to one. The possi-bility of a hereditary influence in some cases issuggested by the report of Dresdale et al. (i954) offour probable cases in two generations of onefamily.

PathologyThe liver, spleen, kidneys and other systemic

organs are usually the seat of chronic venous con-gestion and occasionally of infarction, but the mostimportant changes are to be found in the heart andlungs.The heart is moderately enlarged. Its weight is

usually about one and a half times the normal andseldom exceeds 550 g. in the absence of pulmonaryincompetence. The striking feature is the enormoushypertrophy of the right ventricle, the thicknessof whose wall approaches that of the left ventricleand may even exceed it. There is usually dilatationand hypertrophy of the right atrium, but the left-sided chambers are normal or small.The lung parenchyma usually appears healthy

on naked eye examination, though infarcts aresometimes present and occasionally there is con-gestion and even oedema. The pulmonary arterytrunk and its branches are dilated and intimalthickening is more widespread than usual con-sidering the age of the subject. The segmentalarteries (diameter 2 to 5 mm.) often stand outprominently from the cut surface of the lung.The most significant abnormalities are found in

arteries with a diameter less than i mm. Micro-scopic examination generally reveals widespreadintimal thickening, causing obstruction or evenocclusion of the small arteries or arterioles. The

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September 1956 SHORT: Lone Pulmonary Hypertension 423

post-mortem pulmonary arteriogram (Evans, 195 1;Short, 1956) is always grossly abnormal and showsthat, at least in the final stages, the arterial bed isgreatly restricted by structural disease. In addi-tion, there are abnormal anastomoses. Some ofthese are between adjacent pulmonary arteries,while others link pulmonary and bronchialarteries.The ultimate cause of Lone P.H.T. is still un-

known. Indeed, there is probably more than onedisease included under this diagnosis. Manyauthorities believe that the changes which arefound in the arteries at necropsy are a result of theP.H.T., but recent evidence indicates that thearterial disease is generally sufficiently extensive tobe regarded as the primary lesion. The natureof the arterial disease remains uncertain. Some ofthe changes are undoubtedly thrombo-embolic,while others may be secondary to congenital oracquired lesions in the muscular coat.

SymptomsThe clinical picture of Lone P.H.T. is that of

right heart failure appearing suddenly, most fre-quently in the third or fourth decade, and pro-gressing relentlessly to a fatal termination sometwo years later.The first symptom to appear, and the one which

dominates the picture throughout, is dyspnoea oneffort. A typical story is of a woman finding shecould no longer play five sets of tennis. Six monthslater there were signs of systemic venous engorge-ment and less than three years from the onset shewas dead.Even when exertion is greatly limited, the patientis usually able to lie flat, but occasionally, par-ticularly in the later stages, there may be orthop-noea or paroxysmal dyspnoea. The explanation of

these symptoms is obscure, for pulmonary con-gestion is rare. Attacks of breathlessness may some-times be due to pulmonary embolism.

Although less prominent than dyspnoea, pain inthe chest on effort is experienced at some time bythe majority of patients with Lone P.H.T. It isusually described as a tightness or constrictionacross the chest, which may radiate into the throatand arms. Except for the fact that it is alwaysassociated with dyspnoea, pulmonary angina is in-distinguishable from the pain of coronary arterydisease. Indeed, it probably has a similar origin,though in P.H.T. it is the right ventricle ratherthan the left which suffers from ischaemia, sincethe extra demands of its hypertrophied fibres can-not be met on account of the low and fixed cardiacoutput.

Other varieties of pain in the chest may beencountered, such as a sense of oppression behindthe sternum resulting from pulmonary embolism,

or pleuritic pain from pulmonary infarction. Painin the epigastrium on effort may have its origin inthe liver; so-called effort hepatalgia.The only other symptom which demands con-

sideration is syncope, a history of which is foundin about half the patients with Lone P.H.T. Syn-cope may occur either on effort or at rest. Effortsyncope is due to acute right heart failure. During,or shortly after, exercise the cardiac output in thesepatients falls until it reaches a level where com-pensatory constriction is unable to maintain thesystemic arterial pressure above the critical levelof 50 mm. Hg. (Howarth and Lowe, I953). Theexhaustion which these patients experience onslight exertion is probably due to an inadequateblood supply to the voluntary muscle resultingfrom the same mechanism.The reason why patients with P.H.T. faint at

rest is less certain. Their blood pressure is fre-quently low and it may be that this renders themabnormally liable to the common vaso-vagal syn-cope. Sometimes attacks of unconsciousness ante-date dyspnoea and cause confusion with idiopathicepilepsy.Physical SignsOn examination cyanosis is often evident, but

it is rarely profound and may even be absent.The cyanosis is mainly peripheral, due to the lowcardiac output, so that it is most apparent onexposed parts, such as the lips, cheeks, ears andhands. It is practically never accompanied bydefinite clubbing, except in children. Wherecyanosis is doubtful a short walk usually makes itobvious.

Signs of systemic venous congestion make theirappearance sooner or later in most cases. Theearliest indication of this stage is engorgement ofthe jugular veins. Long before the pressure in thegreat veins begins to rise, however, there is aremarkable change in the form of the venous pulse.The auricular wave becomes exaggerated and inextreme cases may rise as much as io cm. abovethe diastolic level. Because of its quick rise andfall, this wave may be mistaken for the carotidpulsation of aortic incompetence unless it is care-fully timed. With the onset of congestive failurethe auricular wave becomes less prominent andmay ultimately be overshadowed by the systolicwave of tricuspid incompetence.The radial pulse in P.H.T. is almost invariably

small on account of the low cardiac output and theextremities are cold. The blood pressure is usuallylow, but peripheral vaso-constriction may some-times maintain a diastolic pressure of i Io mm. Hg.or higher.

Palpation provides evidence of right ventricularenlargement. The cardiac impulse is as a rule

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424 POSTGRADUATE MEDICAL JOURNAL September 1956

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FIG. i.-The electrocardiogram from a case of LoneP.H.T. showing the pattern of gross right hearthypertrophy.

diffuse, and pulsation extends medially almost tothe sternum and upward to the third left intercostalspace. Palpation in the second space may revealabnormal pulsation of the pulmonary artery andoften an abrupt click synchronous with pulmonaryvalve closure.On auscultation the second sound is usually the

most striking event in the cardiac cycle and is wellheard all over the precordium. At the pulmonaryarea splitting of this sound is usually obvious,though not abnormally wide, and the secondelement, indicating pulmonary valve closure, ismuch louder than the first or aortic component.Triple heart rhythm is generally present and maybe due either to a loud auricular sound or to anaudible third sound.

Other auscultatory findings are variable. In thepulmonary area there may be an abrupt sound orclick in early systole, and this may be followed orreplaced by an ejection murmur. The most fre-quent site for a systolic murmur is the apex, lesscommonly the third or fourth left intercostal space.A diastolic murmur is heard in almost half the

cases of Lone P.H.T. Most commonly it is theblowing murmur of pulmonary incompetence,which immediately follows the second heart sound,and is best heard at the point where the intensityof this sound is greatest. Rarely a delayed diastolicmurmur has been heard.

InvestigationsA slight polycythaemia is usual and haemoglobin

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FIG. 2.-The chest X-ray from a case of Lone P.H.T.showing great enlargement of the pulmonaryartery, slight enlargement of the right ventricle,and somewhat ischaemic lung fields.

values as high as I40 per cent. with red cell countsof 8 million per c.ml. have been recorded in somecases. The arterial oxygen saturation is usuallyreduced to between 80 and go per cent. and mayoccasionally be as low as 70 per cent. The causeof the arterial anoxaemia is not fully understood.A patent foramen ovale is present in some casesand has been held to account for intermittentcyanosis (Edwards et al., I953). A shunt from thepulmonary to the bronchial circulation throughabnormal broncho-pulmonary anastomoses may bethe explanation in other cases.

Another unexplained finding is the discovery innearly half the cases of a polymorphonuclear leuco-cytosis. Counts of 17,000 cells per c.mm. arefrequently observed in the absence of overt pul-monary embolism or infarction.The electrocardiogram (Fig. I) shows the pattern

of right heart hypertrophy, namely, right axisdeviation, a dominant R deflection in the right-sided chest leads (VI, 2), a prominent S wave inthe left-sided leads (V6, 7), and tall pointed Pwaves (P. pulmonale). Sinus rhythm is invariable.On X-ray examination (Fig. 2) the most striking

finding is the dilatation of the pulmonary arterytrunk, which is sometimes aneurysmal. There isusually moderate enlargement of the right ventricleand right auricle, while the left-sided chambers aresmall. The general appearance is reminiscent ofatrial septal defect and the similarity is increasedby the presence of a small aorta in both conditions.

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September 1956 SHORT: Lone Pulmonary Hypertension 425

In Lone P.H.T., however, the right and left pul-monary arteries, though enlarged, are not as pul-satile as in atrial septal defect, and the lung vascu-larity is never increased and generally muchreduced. There may be evidence of old or recentpulmonary infarction (Short, 1951).The crucial investigation is cardiac catheteriza-

tion. By this means it is possible, not only tomeasure the pulmonary artery pressure and thepulmonary arteriolar resistance, but also in mostcases to exclude the presence of congenital heartdisease and mitral stenosis. In Lone P.H.T. thepulmonary systolic pressure at rest generally liesbetween 70 and IOO mm. Hg., though much higherpressures have been recorded. The cardiac outputis usually reduced to about 2.5 1/min., i.e. half thenormal figure.

Angiocardiography' may be useful in excludingthrombo-embolic obstruction of the pulmonarytrunk or its main branches, but it is not yet possibleto demonstrate obstruction of the smallest arteriesand the arterioles during life.

Differential DiagnosisThe diagnosis of Lone P.H.T. is made by ex-

cluding all other causes of P.H.T. The presenceof chronic lung disease is suggested by a history ofrecurrent winter cough and bronchitis or long-standing asthma; by the presence of deep cyanosis,particularly when this is accompanied by obviousclubbing; and by X-ray evidence of structurallung disease. The arterial oxygen saturation islower and the carbon dioxide saturation higherthan in Lone P.H.T. (Platts and Whitaker, 1954).When mitral stenosis is complicated by severe

P.H.T. the differentiation from Lone P.H.T. maycause the greatest difficulty, because in such a casethe characteristic diastolic murmur may be absent.Fortunately, the opening snap and the accentuationof the first heart sound are usually retained. X-rayexamination may show slight left auricular en-largement or calcification of the mitral valve, butit is sometimes necessary to resort to cardiaccatheterization. Occasionally the opposite diffi-culty arises and a case of Lone P.H.T. is mistakenfor mitral stenosis because the third heart soundstimulates an opening snap and rarely because ofthe presence of a delayed diastolic murmur.

Congenital heart disease can only be excludedwith confidence after cardiac catheterization. Itspresence should, however, be suspected when thehistory of disability, cyanosis or a cardiac murmurdates from childhood or infancy.The other important condition which must be

considered before making a diagnosis of LoneP.H.T. is recurrent pulmonary embolism. Recog-

nition of this disease is not difficult if there is aclear-cut history of repeated attacks of dyspnoeaand evidence of long-standing venous thrombosis,but it may be impossible when this evidence islacking. Recurrent pulmonary embolism tends tobe found in an older age group than Lone P.H.T.and seldom shows such high-grade right ventricularhypertrophy in the electrocardiogram (Lenegre andGerbaux, I952).The diagnosis may be suggested by the chest

X-ray, particularly if this shows zones of hyper-translucency or thread-like branches arising froman abnormally dense parent artery. In some casesangiocardiography may be necessary. Emboli tendto obstruct the largest pulmonary arteries and eventhe pulmonary trunk itself, so that filling defectsare usually obvious.Pulmonary embolism (or thrombosis) is a com-

mon complication of pre-existing P.H.T. of anyaetiology, so that it may be impossible even atnecropsy to be certain whether thrombo-embolismwas the cause or the result of the P.H.T.

PrognosisThe majority of patients with Lone P.H.T. are

dead within two years of the onset of symptoms,though survival for as long as I1 years is known.Pregnancy leads to rapid deterioration.

TreatmentVarious drugs, such as priscol, veriloid, khellin

and the methonium compounds, have been shownto lower the pulmonary arterial pressure, but allhave proved ineffective in practice. Stellate gang-lion block has also been performed, but withoutsuccess. If structural changes in the arterial bedare already present when symptoms first appear,the failure of these measures is not surprising.Acknowledgments

I am greatly indebted to Dr. Evan Bedford, Dr.William Evans and Dr. Walter Somerville for theirhelp in the preparation of this paper.

BIBLIOGRAPHYBEDFORD, D. E. (I95I), Proc. Roy. Soc. Med., 44, 597.BRENNER, 0. (1935), Arch. intern. Med., 56, 976.DRESDALE, D. T., MICHTOM, R. J., and SCHULTZ, M.

(I954), Bull. N.Y. Acad. Med., 30, 195.EDWARDS, J. E., HELMHOLZ, H. F., DuSHANE, J. W., and

BURCHELL, H. B. (I953), Proc. Staff Meet. Mayo Clin.,28, 113.

EVANS, W. (I95I), Proc. Roy. Soc. Med., 44, 6oo.HOWARTH, S., and LOWE, J. B. (I953), Brit. Heart J., 5I, 47.LENEGRE, J., and GERBAUX, A. (1952), Arch. Mal. Coeur,

45, 289.PLATTS, M. M., and WHITAKER, W. (I954), Amer. Heart J.,

48, 77.SHORT, D. S. (1951), Quart. J. Med., 20, 233.SHORT, D. S. (I956), Y. Fac. Radiol., to be published.

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