SURGERY IN THE TREATMENT OF CARDIAC DISEASE

For certain cardiac conditions relief may be obtained by extra-cardiac operations, as, for instance, by sympathetic nerve section in cases of angina pectoris or hypertension or by thyroidectomy in cases of heart disease caused by thvrotoxicosis. Improvements in technique in surgery and in anassthesia have, however, made operations on the heart itself a commonplace of modern treat¬ment.

SURGERY IN RELATION TO CONGENITAL HEART DISEASE
It is usually the family doctor or the school medical officer who first makes the diagnosis of a congenital cardiac abnormality. A full examination is then made in hospital to define the nature of the lesion and to assess its suitability for surgical operation. In the application of surgery to the relief of congenital heart disease remarkable advances have been made. New methods are constantly being explored and the combined resources of the biochemist, the physician and the surgeon are now employed as a routine.
In general the risks associated with operative surgery are directly propor¬tional to the extent of the structural defect, and inversely proportional to the judgment, experience and skill of those responsible for the patient. Thus simple ligation of a patent ductus arteriosus by a surgeon who is technically competent in this field, carries a mortality no higher than that of appendicectomy. On the other hand, where the structural defects are numerous and complex the risk is correspondingly increased. Inevitably the mortality is high—even in the hands of an experienced team in a well equipped department. Nevertheless operation may be justifiable because, without such treatment, the prognosis of a particular lesion mav be uniformly grave.
Operations on the heart may be classified roughly into three groups. First and simplest are those which necessitate only thoracotomy without actual operation on the heart. Into this category come ligation of the patent ductus and resection of coarctation of the aorta, as well as those cases of Pallet's Tetralogy in which an anastomosis is made between a subclavian artery and a branch of the pulmonary artery. The hazard in these is generally slight, provided always that the surgeon is experienced in this branch of surgery, that he has the assis¬tance of a competent anaesthetist, a well-trained nursing team and provided that the pre-operative diagnosis is accurate.
In the second group where repair of a septal defect or division of a stenosed pulmonary valve under direct vision is in question, the problems are more formidable. For a time hypothermia was the method of choice, whereby the patient is chilled to a predetermined temperature around 30° C. (86° F.) and after occlusion of the great veins, pulmonary artery and aorta, the heart is arrested by injection of potassium or neostigmine. This allows the surgeon, for example, to open the right atrium and explore and deal with a septal defect. In general, cardiac arrest for several minutes under these hypothermic conditions is harmless because the vital cerebral functions are protected by the low body temperature.
The increasing safety of cardio-pulmonary by-pass techniques, using a heart-lung pump, has led to wide adoption of this method even for closure of simple atrial septal defects. This method is essential in cases involving ven¬tricular septal defects and in all complex malformations. It demands not only costly and complicated apparatus but a highly trained team, not of surgeons only but of technicians, biochemists and blood coagulation specialists. The early high overall mortality, up to 20 per cent., has fallen dramatically to a quarter of that figure in the last few years and to a very low level in the simpler procedures (e.g. closure of atrial septal defects).
The justification for undertaking such operations is the poor prognosis in patients left untreated. It should be borne in mind that complete well-being and lack of limitation of effort in a child, the subject of congenital heart disease, are no sure guides to his future progress. From what is known of the natural history of the different lesions one may predict with some accuracy the probable outcome in individual cases. Thus, for example, children who have a patent ductus arteriosus are continually subject to the hazard of a superimposed subacute bacterial endarteritis—a condition difficult of diagnosis and fatal if untreated which gravely increases the risk of operation. Moreover, those who escape such infection are very liable to develop irreversible cardiac failure in early middle life, by which time operation becomes extremely hazardous. Again, the subjects of atrial septal defect are rarely handicapped in childhood or early adult life, but a large proportion develop cardiac failure in their twenties or early thirties and operation at this stage is much more serious than in the young subject as yet free from pulmonary hypertension. The same considera¬tions apply to patients with coarctation of the aorta, a condition compatible with full activity for many years but which in time leads to the inexorable conse¬quences of sustained gross hypertension with the risk of aortic rupture, cerebral haemorrhage, and left ventricular failure. Hence operation is advisable in the young subject.
In some congenital lesions operation has to be undertaken for the relief of symptoms. For example, in Fallot's Tetralogy the handicap may be such that the child is confined to the house, unable to undertake ordinary activities or to attend school: operation may restore a considerable measure of activity. Again, in cases of severe pulmonary stenosis, in which the right ventricular pressure is extremely high and the muscle grossly hypertrophied, many patients suffer syncopal attacks and there is a constant risk of sudden death on exertion: in these patients also operation has to be undertaken at an early stage. Finally, while operations on very young children are not as yet widely practised, there are certain conditions which lead to progressive cardiac failure at an early age, even in infancy. Among these are occasional cases of coarctation of the aorta of great severity and some cases of patent ductus arteriosus with a large shunt and ;
raised pulmonary blood pressure. Operations for both these conditions hav^ been carried out successfully in infants a few weeks old.
Not every child, the subject of congenital heart disease, is suitable for surgical treatment. A considerable proportion of those deeply cyanosed in early infancy have highly complex malformations irremediable by present methods. For
example, attempts at correction of transposition of the great vessels have been disappointing and there is a number of other conditions (tricuspid atresia, common truncus, etc.) for which treatment at present is impracticable, even with the most skilled surgeon and the most complex equipment. It is appropriate, therefore, to consider some of the common lesions and the indications and risks of their surgical correction.
Patent Ductus Arteriosus.—In patients with uncomplicated patent ductus —usually recognized in early childhood or when the child is examined on first going to school—operation carries a low mortality. It is advisable, preferably between the ages of four and six, in view of the risk of subacute bacterial endar-teritis and of intractable cardiac failure developing in later life. As noted above, occasional cases accompanied by cardiac failure in infancy may have to be operated on at a very early age.
Coarctatlon of the Aorta.—This lesion notoriously shortens life. Opera¬tions for its relief are safest when carried out in childhood or before puberty.' When performed after the age of twenty they are more hazardous and particularly so after the age of thirty. The rising mortality is associated with the progressive arterial degeneration of increasing age. The mortality of operation in skilled hands is low and the results are good. Untreated, these patients are in peril during strenuous activity, and in women during labour, from the risk of aortic rupture, cerebral hasmorrhage and left ventricular failure. On the other hand, if a patient over the age of thirty is found by chance to have coarctation of the aorta and is symptom-free he is best left untreated.
Atrial Septal Defect.—Defects in the atrial septum are common and vary in position and size. The common defect high in the septum (ostium secundum) may be large and may lead to an enormous increase in the pulmonary blood flow, which in turn puts a strain on the right heart and leads to pulmonary vascular changes. Such patients commonly develop symptoms in their twenties and soon develop failure. Operation in skilled hands carries a low mortality, but calls for either the induction of hypothermia and a short cardiac arrest or for cardio-pulmonary by-pass. Before operation is undertaken in patients with an atrial septal defect it is most important that a precise diagnosis be reached, including an estimation of the magnitude of the shunt, the state of the pulmonary vessels, and in particular the site of the defect. Defects low in the septum (ostium primum) are commonly associated with defects of mitral and tricuspid leaflets and with free communications between the two atria and between the two ventricles. Correction of this defect is hazardous and demands assisted circu¬lation from a cardio-pulmonary by-pass pump. A serious operative hazard is permanent complete heart block from an ill placed stitch.
Pulmonary Stenosis.—There is wide variation in the severity of this lesion. Many children with pulmonary stenosis have a loud murmur, little disability and little upset in cardiac haemodynamics. In others the stenosis is extreme, the right ventricular pressure very high and the right ventricular muscle grossly hypertrophied. Operation is not indicated in every case and many people with slighter degrees of pulmonary valvular stenosis may live to an old age with little handicap. On the other hand those with severe stenosis are generally short¬lived. The decision to operate should be reached only after careful assessment of the individual case, utilizing ancillary methods of investigation (cardiac catheterization, etc.)
Operations of two types are practised for its relief. The original method was a blind transventricular section of the valve, yielding reasonably good results but in some respects unsatisfactory. Today the stenosed valve is divided under direct vision through the opened pulmonary artery under hypothermia or with the heart-lung pump. The operative risk is not great and the results excellent.
Aortic Stenosis.—Similar considerations apply to this lesion as to pulmonary stenosis. All grades of severity occur from slight to severe and operation is indicated only in a proportion of cases. The original operations were performed by a blind transventricular valvotomy, but today it is preferable to operate under direct vision through the opened aorta. Such operations on the left heart demand a cardio-pulmonary by-pass.
Ventricular Septal Defect.—In this lesion all grades of severity occur from the classical Maladie de Roger with a tiny orifice high in the septum to patients with a gross defect several centimetres in diameter. Contrary to general medical belief ventricular septal defect is not a benign lesion, and only the smallest defects are compatible with a long unhampered life. Larger defects lead to gross pulmonary plethora, to a rising pulmonary blood pressure and to early failure and death. Repair of lesions of any but minimal size is therefore justifiable in view of the bad prognosis which they carry. Such operations demand the full resources of cardio-pulmonary by-pass techniques and a skilled and experienced team. Detailed pre-operative investigation by cardiac catheterization, etc., .is essential.
Fallot's Tetralogy.—This syndrome is of great importance on two counts :. first, its frequency, and secondly, the severity of the handicap it imposes. It constitutes a high proportion of all cases of cyanotic congenital heart disease surviving into later childhood and early adult life, and in fact some two-thirds of such children have this particular combination of lesions. A much smaller proportion of very young cardiac patients have Fallot's Tetralogy since many cyanosed infants have lesions of other types which in the majority are incom¬patible with prolonged survival. The frequency of this tetralogy in later childhood and adolescence is so great, and its susceptibility to treatment so striking, that every cyanosed child with congenital heart disease should be reviewed with this diagnosis in mind. This entails detailed investigation in a specialized clinic.
Various operations have been practised for relief of the condition. The original operation devised by Blalock—anastomosis of one subclavian artery to the corresponding branch of the pulmonary artery—gave relief from cyanosis and remarkable increase, in effort tolerance to a large number of handicapped children. A similar procedure is Pott's operation, in which a small fenestration is made between the aorta and the pulmonary artery in the form of an artificial ductus. The mortality from these operations is not high and the relief afforded is considerable. The objection to both these operations is that they are simply palliative : they give relief by increasing the blood flow to the lungs but do not correct the other deformities of the tetralogy—the pulmonary stenosis, the ventricular septal defect and over-riding aorta. Accordingly other operations have been devised in an attempt to cure the whole syndrome—division of the stenosed pulmonary valve, and closure of the ventricular septal defect. These demand the by-pass technique described above for cases of ventricular septal defect, while the stenosed pulmonary valve may be divided. These procedures carry a considerably higher mortality than the simple operations first practised, but when successful are believed to be more satis¬factory. Whether the improved results are sufficient to counterbalance the increased risk is a matter of some debate.
Other Congenital Cardiac Lesions.—Of the other congenital lesions many are extremely complicated and few are at present amenable to surgical correction. For example, transposition of the great vessels, in which the aorta rises from the right ventricle and the pulmonary artery from the left, has been tackled by attempts to transplant the two venae cavae and the four pulmonary veins to the respective venous and arterial atria. These operations are in general disappointing and the mortality prohibitive. Similarly operations for tricuspid atresia, common truncus, and comparable malformations are at present beyond the scope of surgery.

EXTRASYSTOLES

Extrasystoles occurring in young people with no other cardiovascular abnormality do not require treatment, and as a rule are resistant to medication. The patient should be reassured as to their innocent nature and should not per¬mit the arrhythmia to interfere with his normal activities. Cases of persistent extrasystolic irregularity occur in healthy young athletes and many people who have had extrasystoles throughout life survive to old age.
Patients who are greatly troubled by sensations due to extrasystoles may require a sedative, such as 30 to 60 mgof phenobarbitone. There is evidence that barbiturates in some cases may diminish the frequency of extra" systoles.
Extrasystoles developing de novo in a patient demand careful overhaul toi exclude organic cardiac disease, and a search must be made for possible exciting factors such as heavy meals before retiring to bed, flatulence, tobacco or caffeine in excess, septic foci in teeth or elsewhere, and digitalis overdosage. During some days following a myocardial infarction, extrasystoles may be conspicuous and should be regarded as danger signals. Since they may herald a paroxysm of ventricular tachycardia or a fatal ventricular fibrillation their suppression advisable using quinidine, 0-2 to 0-3 g. (3 to 5 gr.) four-hourly; or procaineamide may be used, 0-25 g. four-hourly.
Multiple extrastoles may cause a pulse irregularity so great as to simulate atrial fibrillation. If they are not attributable to digitalis overdosage this drug is useful in treatment. To be effective, digitalization must be thorough, and its administration does not differ from that in cases of atrial fibrillation. The continued administration of digitalis to a patient already intoxicated by it is, of course, highly dangerous, and may lead to ventricular tachycardia and sudden death; hence the need to be certain that digitalis is not responsible before starting treatment. Extrasystoles appearing in a patient receiving digitalis should be presumed to be due to the drug till proved of other origin by their persistence for a fortnight after cessation of digitalis therapy. Quinidine sul¬phate, given as above, is useful in some cases, and is a safer drug than digitalis ,n the first week after a myocardial infarction. Coupled rhythm, or pulsus Ugeminus, is usually due to overdosage with digitalis, and this explanation should be assumed correct until it has been dis¬proved. Keeping this rule will avoid accidents from digitalis overdosage.
SINO-ATRIAL BLOCK, NODAL RHYTHM, ETC.
There is no indication for medication in cases of sino-atrial block, or in the other rare disorders such as interference-dissociation. Some of these are prone to occur under digitalis therapy, and should such a cause be suspected the drug should be temporarily withheld.

HEART-BLOCK

The treatment of minor grades of heart-block is directed towards elimination of the cause. Little can be done by drugs to improve the conductivity of a damaged a-v bundle. Many cases are due to excessive dosage with digitalis, potentiated it may be by potassium loss induced by diuretics, and improvement occurs when these are withheld and potassium chloride (a g./day) is given. Others are due to an intercurrent streptococcal throat infection, and subside as this clears up. Many occur in cases of active rheumatic carditis, and for them the treatment is that for rheumatic carditis. A few cases are due to reflex inhibition of the bundle through vagal stimulation, in whom atropine in full doses of i to 2 mg. intravenously may help. In the minority of cases of syphilitic origin, potassium iodide may be of benefit, but actual gummata of the bundle are very rare. Partial or complete heart-block occurs as a relatively infrequent sequel to acute myocardial infarction, and is generally transient. Recently treatment of this type with corticosteroids has been widely advocated, but the self-limiting course in untreated cases renders assessment of the value of the treatment difficult. In the large group of cases due to ischasmia from arterial degeneration, we have no specific drug of proved value. Simple prolongation of the a-v conduction time, or the occurrence of dropped beats are of no moment as regards the mechanical efficiency of the heart. Patients with long-standing 2 : i heart-block may experience no limitation of effort, and demand no special treatment. It is to be emphasized that digitalis is contra-indicated in partial heart-block, as the drug may depress the bundle further and aggravate the condition.
Established complete heart-block is likewise not amenable to drug therapy. It is usually due to scarring of the bundle, which is irreparable. The manage¬ment of such a case, however, is important: the patient should be warned to live within his reserve, and cautioned as to the risks of strenuous exertion, such as running upstairs, lifting heavy articles, etc. Undue exertion can in such patients lead to syncope since the heart cannot accelerate and increase its output to meet the demands for increased blood flow to the tissues, and the cerebral circulation suffers accordingly.
High-grade heart-block in an unstable state is manifested clinically by recurrent classical Adams-Stokes attacks : these can sometimes be prevented by isoprenaline or, more effectively, by electronic pacemakers.

PAROXYSMAL TACHYCARDIA

Supraventricular Paroxysmal Tachycardia occurs frequently in people with no other discoverable abnormality. It is also seen in various pathological conditions—rheumatic heart disease, toxic goitre, etc., and in such an effort must be made to deal with the exciting cause.
Various measures may cut short a paroxysm. There are many methods, and patients soon learn which procedure is most effective. That which meets with success varies in individual cases, but remains fairly constant for any particular patient. Lying down flat, bending the head low between the knees when seated on a chair, holding the breath, attempting forced inspiration or expiration with nose held and mouth closed, pressure over the abdomen, and vomiting, are all procedures that patients may find useful in cutting short attacks. The physician may stimulate the vagus reflexly and strongly by pressure over the carotid sinus on one or other side, and this frequently arrests the paroxysm : the patient should lie on a couch, and pressure with the finger-tips of one hand should be exerted gently over a point level with the upper border of the thyroid cartilage at the anterior border of the sternomastoid. Meanwhile the heart should be auscultated, and abrupt slowing or cessation of the sounds is the signal for immediate release of pressure. If a first attempt is ineffective, success may follow repeated attempts or stimulation of the sinus on the other side. Cases resistant to sinus stimulation may yield to reflex vagal stimulation through the fifth nerve, from pressure on the eyeballs. Ocular pressure, however, is un¬pleasant and painful, and is now seldom employed. A tight abdominal binder is sometimes effective, especially in children.
In cases in which simple measures are ineffectual, attacks may sometimes be terminated by full digitalization, e.g. by the intravenous injection of 0-75 to i mg. of digoxin, the action being manifest in twenty to thirty minutes. It is essential before such intravenous therapy to be certain first that the patient is not already having digitalis treatment, and secondly that the rhythm is in fact supraven-tricular; digitalis is not a drug to use lightly in ventricular tachycardia. If this fails, quinidine sulphate by mouth in doses of 0-3 g. (5 gr.) three or four times a day may be effective. Hypodermic administration of 15 to 20 mg. morphine may secure needed rest for an anxious and exhausted patient. Supra-ventricular tachycardia is common in infants, in whom it may lead to severe congestive failure, and in whom digitalis in appropriate dosage is highly effective. Digitalis in anything like the adult dose is highly dangerous, and the average digitalizing dose for infants is 0-04 mg./lb. (0-09 mg./kg.) body-weight, given as the elixir in divided doses four or six-hourly.
With the development of pain or of symptoms and signs of congestive failure indicating exhaustion of the heart muscle, the need to arrest the paroxysm becomes more urgent. Should other measures have failed, treatment by intra¬venous quinidine or electrical cardioversion as practised for ventricular tachy¬cardia, may be required. The parasympathomimetic drugs (methacoline and carbachol) are now rarely used.
Attacks tend to cease spontaneously and are generally of short duration— minutes or hours. Every day that passes in a persistent case renders spontaneous arrest more likely, and whatever medicament is being used will probably be given the credit for the cure.
Ventricular Paroxysmal Tachycardia is less common than the other form, and generally occurs in older patients with grave myocardial disease, e.g. after recent coronary infarction. It may also occur from gross overdosage with digitalis. One rare form, however, is innocent and occurs in relation to exercise in apparently healthy people. In general, vagal stimulation and parasympatho¬mimetic drugs are useless in this form of tachycardia and treatment by quinidine, procaineamide or electrical cardioversion is required. Quinidine given orally in doses of 0-2 to 0-3 g. (3 to 5 gr.) two hourly is sometimes effective : the rate during the paroxysm may fall gradually under quinidine before normal rhythm is abruptly restored. Treatment in cases of ventricular tachycardia with grave cardiac disease and gross failure is more urgent than in the average case of supraventricular origin, and in these patients a quinidine sulphate drip given intravenously is of great value. Quinidine sulphate in a concentration of 3 g. (45 S1-) m 600 nu- °f saline is given by slow intravenous infusion at the rate of about 100 ml. per hour. It is essential that a close watch be kept upon the heart rate, and if possible electrocardiographic control or better, monitoring on an oscilloscope, is advisable. Gradual slowing of the high ventricular rate with sudden reversion to normal rhythm occurs in many cases after administration of from 0-3 to 1-5 g. (5 to 20 gr.) of the drug . Once normal rhythm has been restored, quinidine sulphate by mouth should be continued as described below.
Procaine has an action comparable to quinidine in ventricular ectopic rhythms, but its cerebral excitant action precludes its use m the unansesthetized patient. Its derivative, procaineamide, is devoid of this cerebral action, and can be used for treatment of extrasystolic arrhythmias. It is given orally in capsules ofo'25 g., or intravenously in 50 to 100 mg. doses repeated at intervals of a few minutes up to a total of i g. Reversion to normal rhythm, when it occurs, may be sudden. In some patients gross extrasystolic disturbances, even fatal ventricular fibrillation, may be provoked. Electrocardiographic control is most desirable. The blood pressure should be repeatedly estimated during the injection, since hypotension is a common side-effect. As with quinidine, this drug is unsuitable for use in general practice.
Prevention of Attacks.—Patients who have recently had attacks of paroxysmal tachycardia, or who are liable to repeated attacks, are generally benefited by maintenance doses of 0-2 to 0-3 g. (3 to 5 gr.) of quinidine sulphate several times daily over a period of weeks. Any exciting factor (excess of tobacco, caffeine or alcohol; thyrotoxicosis; septic foci in teeth or tonsils, etc.) should be attended to. Many patients are resistant and attacks recur at intervals over many years without serious effects on the health. In them continued quinidine therapy is unnecessary, but they should be given a supply of the drug for use during an attack. In cases of supraventricular paroxysmal tachycardia, reassurance as to
the innocent nature of the attacks is very important.
The smooth controlled action achieved by this method is clearly shown.
Cardwversion.—The technique of cardioversion, developed over the last few years, is becoming increasingly widely employed as the apparatus becomes available in this country. (The British Heart Foundation has gifted cardio-verters, each costing about ,£1,000, to teams in centres all over Britain.) In principle, the method employs a brief high-voltage (3,000 to 5,000 volt) Direct Current shock to depolarize the heart, so that on repolarization the sinus node with its highest rhythmicity reasserts its dominance. It is essential that the shock be timed to fall in the " safe period ", during early ventricular systole, since a shock at the end of systole (near the apex of the T-wave of the E.C.G.) may produce ventricular fibrillation, and shocks during atrial systole induce atrial fibrillation. Exact timing is secured by using the R-wave of the E.C.G. to trigger the shock, after a built-in predetermined delay of a few milliseconds-The voltage is built up in a condenser after stepping-up and rectification of ordinary mains A.C. supply, and the discharge is smoothed and prolonged bv an impedance in the circuit. A range of voltage is available, and calibration of the
energy used is in watt-seconds.
In use, the patient is connected to the built-in E.C.G., anesthetized briefly with intravenous thiopentone, and given one or more shocks at increasing voltage from large electrodes held against the chest so that the current traverses the heart. Preliminary use of quinidine, and suppressive doses after restoration of normal rhythm are advisable.
The results are impressive. Series running into three figures have been reported from various centres, from. which it is clear that the method is safe, and highly effective. Embolism is not a serious hazard. In atrial fibrillation over 80 per cent. of cases revert to sinus rhythm. Unfortunately, more than half of them relapse to fibrillation later. Repeated cardioversion in such individuals can, however, be undertaken.
Cardioversion can be used not only in atrial fibrillation, but in other disorders of atrial or ventricular rhythm—flutter, atrial and ventricular paroxysmal tachycardia, and ventricular fibrillation. For atrial fibrillation and flutter and for ventricular tachycardia it is probably safer than conventional drug therapy.
Beta-adrenergic Blockers.—Two types of sympathomimetic receptors are known, of which the beta group are concerned in cardiac ventricular excitability. Specific agents blocking these receptors have been devised: the first (prone-thalol) while effective was found to have carcinogenic effects .in rodents in long-term use, and has been withdrawn. Its successor, propranolol, is free from this drawback, and has been used for control of obstinate arrhythmias, and for treatment of angina. It has a specific additional use in the rare form of cardio-myopathy which mimics aortic valvular stenosis. Its value has not been finally established, but in oral doses of 10 to 20 mg. it is worthy of trial in cases of atrial fibrillation where digitalis fails to control an excessive ventricular rate, in recurrent paroxysmal tachycardia, and in gross extrasystolic arrhythmia. In angina it has been shown on occasion to increase exercise tolerance and reduce the frequency of attacks.

ATRIAL (AURICULAR) FLUTTER

Unlike atrial fibrillation the disordered atrial mechanism in this condition is influenced considerably by digitalis. In doses sufficient to produce ventricular slowing, this drug also converts nutter to fibrillation in most cases. Stopping the drug once fibrillation has developed is followed in about one-third of the cases by return to normal rhythm; in another one-third the rhythm reverts to flutter;
in the remainder fibrillation persists indefinitely. If flutter recurs, a second course of digitalis may succeed in establishing normal rhythm, or cardioversion or quinidine may be tried. If atrial fibrillation persists, it is treated in the usual way, and again cardioversion or quinidine may be tried.
Digitalis if used is given as for atrial fibrillation. Whenever marked slowing occurs together with total irregularity at the apex, fibrillation may be assumed to have developed. This may ensue after a single intravenous dose of strophanthin or digoxin, but it is more usual to give digitalis orally over a period of some days. Electrocardiographic control is desirable. When fibrillation supervenes, digitalis is stopped for a few days-and a return to normal rhythm awaited.
An alternative method is to use quinidine. After preliminary digitalization, to slow the ventricular rate and abolish congestive failure, quinidine is given in similar dosage and method as for atrial fibrillation. Quinidine slows the atrial rate, so that a rate originally between 250 and 300 per minute falls gradually —it may be to below 200 per minute. At this stage there is a danger that the ventricles may follow the full atrial rhythm (1 : 1 flutter) instead of responding to every second, third or fourth atrial cycle as at the beginning of treatment. Should this occur a dangerous tachycardia at 180 to 200 per minute may occasionally arise. The slowing of the atrial rhythm to 200 or thereabouts is frequently followed by abrupt resumption of normal rhythm. Large doses of the drug are then stopped, and after twenty-four hours small doses of 0-2 g. (3 gr.) once or twice a day are given and maintained for a few weeks.
It has been our practice to use digitalis for cases of nutter in the first instance, quinidine being reserved for those who fail to respond to digitalis. In either case, should normal rhythm be restored, its duration depends on the same factors as apply in cases of fibrillation treated with quinidine. Recurrence of flutter or fibrillation at an early date is likely in patients with grossly enlarged hearts or old-standing disorders of rhythm, and in those in whom a toxic factor is still operative, such as hyperthyroidism.

THE CARDIAC ARRHYTHMIAS

The presence of a cardiac arrhythmia is an indication for treatment only when the abnormal rhythm interferes with cardiac efficiency. Sinus arrhythmia is normal and requires no treatment. Occasional extrasystoles, or even short bouts of paroxysmal tachycardia, may occur in healthy hearts with no effect on cardiac efficiency. Minor degrees of heartblock and atrial fibrillation with a slow ventricular rate are indications of cardiac damage, but do not in themselves limit the capacity for effort. In treating all arrhythmias attention should be directed primarily to the maintenance of ventricular efficiency, and in some atrial disorders, e.g. fibrillation, this can be done without fundamental change in the abnormal rhythm.

HYPERTENSION IN PREGNANCY

High blood pressure during pregnancy occurs under two different circum¬stances : a woman with established hypertension may become pregnant; or a patient with a normal blood pressure may in the course of pregnancy develop a toxeemia of which hypertension is a sign.
If a patient known to have hypertension becomes pregnant she must be kept under close observation throughout its course. Apart from the dangers of hypertension itself, the risk of a superimposed toxaemia of pregnancy is greatly increased in hypertensive patients, nearly half of whom develop toxaemia. With close ante-natal supervision any tendency for the pressure to rise as the pregnancy progresses can be detected, and appropriate measures instituted. In the milder cases enforcement of rest, restriction of sodium in the diet and the use of reserpine usually suffice to maintain the pressure at a safe level. The persistence of a high pressure, above, sav 150/100 for several weeks at a time, leads to deterioration in the health of the mother and commonly results in the death of the fcetus, so that it is important that the hypertension should be vigorously treated. The ganglion-blocking agents are contraindicated in this condition, as they tend to increase foetal mortality, but treatment with reserpine and chloro-thiazide should be continued for the remainder of the pregnancy. The advisability of terminating pregnancy should be considered when persisting hypertension is associated with albuminuria and a progressive gain in weight due to fluid retention, particularly if the foetus is viable.
Hypertension may persist into the puerperium and occasionally dangerous acute hypertensive episodes occur during that stage. These demand treatment along similar lines.

HEART DISEASE AND PREGNANCY

Pregnancy is a natural hazard to the young female cardiac patient, and the frequency of the problems to which the association of the two conditions gives rise may be gauged from the fact that between 1-5 and 3 per cent. of all women attending ante-natal clinics are found to have cardiac lesions. The great majority (90 per cent.) of these are cases of rheumatic valvular disease; a much smaller proportion have congenital malformations; ischasmic heart disease in the pregnant woman is rare.
Pregnancy imposes a severe strain on the cardiovascular system of handi¬capped patients and in a considerable proportion the heart cannot withstand the additional burden so that cardiac failure in one form or another ensues. The increased load on the circulation is in part imposed by the metabolic demands of the pregnant state, but there are also hasmodynamic factors of considerable importance. The large placental circulation acts as an arterio-venous shunt, imposing a considerable burden on the heart. Further, during pregnancy the blood volume increases progressively in the early months to reach a peak at or about the 32nd week and thereafter slowly falls towards normal. The load imposed by this increased circulating volume is thus at its maximum, which explains why disability is usually maximal at that time and that thereafter symptoms may regress.
The diagnosis of heart disease in a woman seen for the first time during pregnancy can be difficult. Every cardiologist can recall patients in whom murmurs heard during pregnancy suggest a valvular lesion and yet on re-examination after delivery no murmurs are heard and there is no clinical evidence of heart disease. It is probable that the increased cardiac output associated with the high blood volume during pregnancy is responsible for these transient murmurs.
The best guide as to how a woman with a cardiac lesion will withstand pregnancy is afforded by her previous history. The first question is to determine how far she was handicapped before the pregnancy began. The woman who previously had little or no disability is unlikely to come to serious harm during its course, and conversely the woman who before pregnancy was already seriously handicapped or in failure will certainly be in danger so long as the pregnancy continues, and in fact well into the puerperium. Other factors to be considered are first the age of the patient, as the risks increase steeply with advancing age ; secondly, the parity, since successive labours are likely to be shorter and to impose less burden on the heart; thirdly, the previous obstetric history in so far as the cardiac complications of pregnancy were concerned ;
fourthly, her circumstances, such as wage-earning and domestic duties which may or may not permit her to rest adequately; fifthly, the co-existence of other complicating disorders such as anaemia and renal disease; and sixthly, obstetric factors (disproportion, etc.).
One class of case constitutes a striking exception to these general rules— the patient with a tight mitral stenosis, probably with a small heart and normal cardiac rhythm, who develops episodes of acute paroxysmal dyspnoea due to pulmonary congestion secondary to left atrial failure. Although such patients may have in the intervals little breathlessness or other handicap, they are in peril, and it is among these individuals that a great proportion of the fatal cases arise. In such patients mitral valvulotomy during pregnancy may save life.
Probably the most important single factor in the safe management of the pregnant cardiac patient is regular careful ante-natal supervision. In most hospitals there is a close liaison between the obstetric unit and the cardiologist. Thus the early signs of incapacity or failure can be detected and dealt with, decisions as to interruption of pregnancy can be taken jointly, and during the final obstetric management of the case the advice of the physician will be available to deal with heart failure or any other emergency which may arise either at term or in the puerperium. With such care the maternal mortality can be reduced to a very low figure in comparison with the high mortality among women who continue their pregnancy unsupervised and who seek medical advice only when driven to do so because of serious incapacity. Although patients seek help at all stages of pregnancy it is convenient to consider the management of those seen for the first time during each of the three trimesters. Some broad guiding principles, however, may first be considered.
The general rules as to obstetric management are relatively simple. In the first place, interruption of the pregnancy, if this is deemed necessary, should not be carried out later than the third month ; thereafter the risks of interference are greater than the risks of allowing the pregnancy to proceed, so that a patient seen for the first time in the fourth month or later even if she is in failure should on no account be subjected to therapeutic abortion. Again, when as the result of good management, a patient has successfully reached the last few weeks of pregnancy, a decision has sometimes to be taken regarding the manner of delivery, whether per vaginam or by Csesarean section. The consensus today is against Cassarean section, which formerly was carried out about the 37th week as an operation of election to spare the mother the strain of labour. The risks involved, however, are greater than if the woman is allowed to go to term, and the infant mortality is considerably higher. Provided there are no obstetrical complications, a forceps delivery can usually be achieved without difficulty, and fortunately many of the infants born to these women are small. It should be emphasized that the more serious the patient's cardiac condition appears to be on admission to the obstetric unit, the more important it is not to interfere with the pregnancy until the cardiac failure has been controlled; only then should obstetrical interference be considered. This rule applies at all stages of preg¬nancy. As stated above, interruption of pregnancy after the third month is unwise. A decision to perform sterilization should not be used as an argument in favour of Csesarean section; this can be carried out at a later date when the hazards of pregnancy have been surmounted. It should be remembered that the risks are not over when the woman has been delivered of her child; cardiac failure may supervene in the puerperium and may prove fatal.
First Trimester.—During the first trimester important decisions must be taken regarding the management of the individual patient. In these the prac¬titioner is guided by the factors enumerated above, forecasting the likelihood of a stormy or peaceful pregnancy from the previous history. Where there has been no previous disability a patient seen in this period should be reassured and supervised at regular intervals ; as the pregnancy advances she should be encouraged to rest more than the average pregnant woman, particularly in the later months. When there has been some previous handicap or the history of some cardiac complication in a previous pregnancy, the risks of continuing the pregnancy should be explained to the patient and her husband and the advis¬ability of therapeutic abortion considered. When the patient has been seriously incapacitated or has developed cardiac failure, or when serious failure has complicated previous confinements, termination of pregnancy should be strongly advised. If the patient is already in failure when seen, as emphasized above, no interference with the pregnancy should be permitted until the failure has been relieved. Thereafter its termination is advisable.
Second Trimester.—From the fourth month onwards interference with the course of the pregnancy is contraindicated, and the management of the patient consists of the assessment of the degree of handicap and of the treatment of cardiac failure if this is present. Even in patients with little disability it is wise to insist on additional rest in the afternoons and at week-ends and in those more seriously affected complete rest in bed may have to be imposed even at this early date. Appropriate treatment with diuretics, salt restriction and digitalis will assist the patient through the remaining months of her pregnancy.
Third Trimester.—Patients who pass through the first six months of pregnancy without ill effect and who develop signs of failure in the third trimester will require admission to hospital and treatment, but in general they may be expected to improve in the last weeks of the pregnancy and may be less upset by labour than might be anticipated. It should be reiterated that no matter how severe the failure or how desperate the handicap surgical obstetrical interference at this stage is contraindicated.
Puerperium.—Cardiac failure after delivery is a very serious matter : the spontaneous amelioration which occurs with the reduction of the blood volume in the later weeks of pregnancy cannot be expected, since the blood volume has already returned to normal. The death rate among patients in failure at this stage is high and the failure is often refractory to standard treatment. When for one reason or another breast-feeding is undesirable, it should be remembered that cestrogens given to suppress lactation favour water and sodium retention.
Advice on Child-bearing.—Young married women and their husbands frequently ask advice on this matter, and the doctor must be prepared to guide them to the best of his ability. It is a great mistake to defer pregnancy in a young patient who is married and desires a child. If she is fit to have a child she should be encouraged to have one, since with each year that passes she will become older and less able to withstand the strains involved. Pregnancy carries no undue risk for the woman who is little handicapped by her lesion, though for the woman whose capacity for effort is already restricted pregnancy is a grave hazard. A thoughtless ban imposed by a doctor playing for safety may be productive of much distress and unhappiness, and it is unfortunate that such prohibitions are widely enforced without due consideration. When the patient's handicap is definite though not gross, and when the practitioner anticipates that —at least in the later weeks of pregnancy—the patient is likely to be in failure and confined to bed, the position should be explained to the prospective mother. Many women are more than willing to accept such a risk in their desire to have a child, but in such patients repeated pregnancies should be discouraged. One baby may be safely achieved; a second child after a year or two may be feasible and on family grounds is highly desirable to avoid the disadvantage of the only child.
It is commonly forgotten that the burden imposed by child-bearing does not cease with delivery. Caring for the child during infancy and early childhood may impose on the mother a greater strain than the pregnancy. Where there are two or three children in the family under the age of five the physical load on the mother with cardiac disease may be formidable.

SECONDARY HYPERTENSION

Cases of hypertension secondary to an identifiable cause fall into two broad groups ; those in whom the cause may be removed with the probability of relief of the hypertension, and those for whom no radical treatment is feasible. Included in the first group are coarctation of the aorta, phseochromocytoma, and cases of strictly unilateral renal disease.
Unfortunately, the majority of patients with secondary hypertension fall into the second category, radical treatment of the underlying cause being impossible. In this group are bilateral kidney disease, particularly chronic glomerulonephritis and pyelonephritis, the latter ranking as one of the com¬monest renal causes of hypertension. In addition there are cases secondary to the chronic degenerative renal lesions of diabetes (Kimmelstiel-Wilson syndrome) and cases of renal amyloidosis. The management of high blocd pressure in such conditions differs from that of essential hypertension only in respect of the limitations imposed on drug therapy by renal damage. The slow excretion of hypotensive drugs by damaged kidneys, and the reduction of glomerular- filtration rate which may result, necessitate particular care in the use of these potent drugs, as otherwise renal failure may result.

MALIGNANT HYPERTENSION

MALIGNANT HYPERTENSION
Patients with extreme hypertension, with diastolic pressures of 140 or over, and with gross retinopathy (haemorrhages, exudates and papilloedema) fall into the category of malignant hypertension. Such patients commonly have serious secondary damage to brain, heart or kidney, the last leading to impaired renal function which is rapidly progressive. The prognosis is grave : the great majority of untreated patients die within two years and a considerable proportion within one year. Energetic treatment is a matter of urgency and the favourable response which may follow warrants close attention to detail in the management of each individual patient. The results of treatment with hypotensive drugs are better than those formerly obtained by lumbo-dorsal sympathectomy, and the prognosis has been greatly improved by their advent. There is a substantial proportion of cases, however, in whom the disease pursues a relentless course and unfortunately many patients are debarred from effective therapy by the extent of their renal damage. Impaired renal function implies delayed excretion of the drugs and at the same time a reduced renal blood flow may have adverse repercussions on renal function. Careful assessment of renal function in each individual case is therefore an essential preliminary to the institution of hypo-tensive treatment. When renal function is seriously impaired, and when the blood urea concentration has already reached 90 mg. per cent. or above, treatment must be cautious and it is unlikely that a satisfactory result will be obtained.
For reduction of pressure in this group either the ganglion-blocking agents (mecamylamine; pempidine) or an adrenolytic drug (guanethidine; betha-midine) may be used. It is wise to bring the pressure down gradually over a period of days rather than to attempt a drastic reduction within a short period, since such abrupt hypotensive effects may be followed by thrombosis in the cerebral or coronary arteries, or by a sharp deterioration in the already impaired renal function. Even a moderate reduction in the diastolic pressure, say from an initial level of 150 to 120, is a considerable gain to the patient and may arrest the progress of the necrotizing changes in the small arterioles which are the cause of the evil sequela; of malignant hypertension. In many patients such a moderate reduction in pressure is all that can be attained, though in others it may be possible to bring the diastolic pressure down to approximately normal.
Once the patient with malignant hypertension has been brought under control he must be most carefully supervised during the ensuing months and years. It is only by close attention to the detail of treatment that the full life-saving potentialities of hypotensive treatment can be realized. A considerable proportion of patients with this previously fatal illness can be kept alive and in relatively good health for a decade or more. The survival rate is largely a reflection of the skill and care with which the treatment is supervised.
Today such operations as sympathectomy and adrenalectomy are comparatively rarely performed, and in general only on patients in whom medical treatment has failed to achieve a significant reduction in pressure.

HYPERTENSIVE CRISES

HYPERTENSIVE CRISES
Patients with severe hypertension are liable to intercurrent episodes in which the pressure rises temporarily to a very high level, and during this phase cerebral or cardiac symptoms may be prominent: for example, transient hemiplegia or monoplegia, amaurosis, intense headache or epileptiform fits of hypertensive encephalopathy may occur over a period of hours or days, or the patient may develop acute left ventricular failure with life-threatening cardiac asthma. Such attacks must be treated energetically and a number of remedies are available for this purpose. A prompt reduction of pressure can be achieved with pentolinium given intravenously in a dose of 0-5 to i mg. This will produce a fall in pressure which lasts for some six hours. The blood pressure should be taken repeatedly at short intervals during and after the injection so that the dose of pentolinium may be varied in accordance with the response obtained. In general it is sufficient to reduce the diastolic pressure to approximately 100 mm. Hg.; it is unnecessary and unwise to attempt to reduce the pressure to the normal level. Repeated doses of pentolinium by the intravenous or subcutaneous route may be necessary to control the pressure.
The patient meanwhile should be nursed in bed in a quiet room and sedated with barbiturates such as amylobarbitone 0-2 g. (3 gr.) orally or phenobarbitone soluble 0-2 g. (3 gr.) by intramuscular injection. Appropriate specific treatment is simultaneously given for cardiac asthma or any other complication present.

PRIMARY OR ESSENTIAL HYPERTENSION

In the management of any patient with a significant hypertension, irre¬spective of whether or not a decision is reached to treat him with drugs, certain general principles apply. These include advice regarding the general regulation of his life in respect of work, physical activity and rest ; the reduction of obesity when such is present; the restriction of salt in the diet; and not least "In importance the securing of the patient's co-operation and the allaying of the natural apprehension of a sensitive individual regarding his disorder and its possible consequences.

GENERAL MANAGEMENT

It is probable that the pace of modern life and the stress and strain to which an is subjected are in large measure responsible for his liability to hypertension and to the acceleration of its progress. It is reasonable, therefore, to counsel the victim of hypertension to moderate his activities reasonably both as regards recreation and work. While the doctor can do much to guide a patient in this respect, there is a danger that well-meaning but ill-advised interference in a • man's affairs may lead to great hardship. If a man's livelihood and the welfare of his family depend on his earning capacity it is probably more harmful to insist on his giving up his work than to allow him to carry on with some sensible restrictions. The personal qualities of the doctor, his wisdom and judgment are of the greatest importance in the management of hypertension. From the nature of things business and financial worries are inseparable from our lives, and it is impossible for a man to continue in an active earning capacity and to avoid such traumata. Modification of activities rather than drastic alteration is generally the best counsel. Even the most drastic curtailment of activity in a severe hyper¬tensive is no guarantee that life will be prolonged, and even if it were, " length of days can be purchased at too great a price ". It is wiser to allow the patient to continue with some of his work, restricted possibly in scope, than to compel premature retirement with its legacy of frustration, financial worry and boredom.
Weight Reduction.—As in valvular disease and coronary artery disease, obesity in the hypertensive imposes an added and avoidable cardiac burden. Many hypertensive patients are obese and should be encouraged to reduce their weight, aiming at a figure rather under the ideal weight for age, sex and height as given in conventional tables. In those who already have cardiac symptoms, loss of weight may be accompanied by a remarkable increase in exercise tolerance.
Salt Restriction.—There is good evidence that retention of sodium plays a part in the genesis and maintenance of a raised blood pressure. For this reason it is logical to advise some restriction in consumption of salt. It should not be added to food at table, and salty foods should be avoided. There is no need for drastic restriction, however, and the very strict salt-poor diets contain¬ing say 0-2 g. of sodium per day, e.g. the Kempner rice diet, have onlv a limited place in therapy and none in prophylaxis. On such drastic regimens the blood pressure certainly falls steeply after a few days, but most patients find such meals intolerable for protracted use, and there is evidence that with continued use of the rice diet there is a risk of striking deterioration in renal function.

DRUG TREATMENT OF HYPERTENSION

Preliminary Assessment of Case.—When a patient is diagnosed as having high blood pressure, a decision must be made regarding the necessity for and feasibility of drug treatment. To this end various simple investigations should be carried out. In the first place an estimate should be made of the patient's basal pressure, taken as already described. He can then be classified as a mild, moderate, severe, or gross hypertensive on this basis. Attempts to assess the true basal pressure with the patient heavily sedated with a barbiturate (say amylobarbitone 0-2 g. three times at hourly intervals) have fallen into disuse, since the lability of the pressure under these circumstances bears little relation to the effects of treatment.
The next point is to determine what effects, if any,»have been produced by the hypertension on the so-called target organs—brain, retinse, heart and kidney. Evidence of affection of these organs can be taken as an indication for vigorous treatment, irrespective of the actual height of the blood pressure. For example, the patient who has marked cerebral symptoms, whether they be transient paresis of angiospastic type, hypertensive encephalopathy or a frank cerebrovascular accident, is in urgent need of treatment. The size of the heart determined clinically and by radiological examination, and the extent of the hypertrophy and degree of muscle damage as shown electrocardiographically are indices for therapy. The examination of the retina; is a valuable procedure, particularly useful in the detection of the so-called malignant hypertension, in which papilloedema is present in addition to alterations in calibre of vessels, hasmorrhages, and exudates. An estimation of kidney function should be made, since early renal involvement is an indication for vigorous treatment and severe renal damage may preclude the use of hypotensive drugs. Finally, before treatment of hypertension is initiated, it is essential to establish that the case is indeed one of primary or essential hypertension and not secondary hypertension due to a remediable cause.
Hypotensive Drugs and their Use.—A wide variety of drugs is available today. In addition to their approved or official names, each is marketed by drug firms under their own trade names and this causes confusion. New preparations which are widely advertised appear with embarrassing frequency, each claimed to have advantages over their predecessors, so that the bewildered doctor is tempted to switch from one to another and fails to acquire true familiarity with any one of them. It is most desirable that the practitioner should make himself thoroughly acquainted with the action of one or two drugs of each of the groups to be described, and that he should confine his prescribing to those drugs with which he is familiar. It should be emphasized that the evaluation of the action of a new drug should be carried out in properly controlled large-scale therapeutic trials, and that the piecemeal trying out of drugs by individual doctors in practice or in hospital has little to commend it, and may in fact lead to quite erroneous conclusions.
The drugs available may be grouped as follows :
(1) Centrally acting (depressant) drugs of the Rauwolfia group.
(2) Ganglion-blocking agents, which block the transmission of impulses at both sympathetic and parasympathetic ganglia.
(3) Adrenolytic agents, acting solely on the sympathetic effector mechanism.
(4) A mixed group comprising hydrallazine, veratrum, and dehydrogenated ergot alkaloids.
(5) Dopa decarboxylase inhibitors.
Rauwolfia Compounds.—These drugs are derived from the dried roots^ of the Indian shrub Rauwolfia serpentina. They have a moderate hypotensive action which is centrally mediated. They are active given by mouth and their action develops gradually. The full effect may not be manifest for several weeks with standard doses, but once a maximum effect has been attained it is often possible to maintain this indefinitely with considerably reduced doses. While of value in cases of moderate hypertension, particularly in those patients in whom anxiety is prominent, they have side-effects which are a considerable dis¬advantage. Their usual tranquillizing effect is salutary, but they may on occasion produce considerable and sometimes suicidal depression. Less serious and less persistent undesirable effects are their tendency to cause nasal congestion and diarrhoea. The drug may be administered as the pure alkaloid, reserpine, in a dose of 0-25 mg. three times daily, or as one of the preparations of which a considerable number are on the. market (reserpine, rauwolfia); it is claimed that a derivative, methoserpidine, preserves the hypotensive action of the parent drug but is less prone to produce depression. As with many of the hypotensive agents described below the effect of reserpine may be enhanced by the simul¬taneous administration of a thiazide drug (chlorothiazide, hydroflumethiazide).
The main value of the Rauwolfia compounds lies in the treatment of tense, anxious patients with moderate hypertension. They are also of value as adjuvants to the more powerful agents to be described below. In any individual case the assessment of the success of the Rauwolfia treatment can be reached only after a trial of six to eight weeks. By this time it should be clear whether the drug is producing a satisfactory response without untoward side-effects. Should a satisfactory response be achieved it is usually possible to reduce the dose considerably, perhaps to a single 0-25 mg. tablet daily, for long-term treatment. It should be kept in mind that the depressant action of Rauwolfia may result in a gradual deterioration in higher cerebral functions, loss of drive and initiative and loss of qualities necessary for the successful prosecution of business life, which can be very serious for the patient. Such deterioration may be so gradual as to escape notice or may be attributed to the progress of the hypertension. It is more frequently detected by the patient's family or employer than by either the doctor or patient himself.
Ganglion-blocking Agents.—While the principle governing the use of. ganglion-blocking agents would appear to be sound and to promise good results in treatment, the number of members of this group which have been successively introduced (hexamethonium ; pentolinium ; mecamylamine ; pempidine) is sufficient evidence that none has proved satisfactory. Some are absorbed so erratically from the gastrointestinal tract that accurate oral dosage is impossible;
others are drugs to which tolerance is readily acquired so that increasing doses are necessary to control the pressure; all have side-effects of greater or less intensity which are in part at least due to the essential action of the drugs.
These drugs block not only sympathetic but also parasympathetic ganglia, so that side-effects on the parasympathetic nervous system are prominent. These include dryness of the mouth, dilatation of the pupil, difficulty in accommodation, and constipation progressing in extreme cases to intestinal ileus. In addition their effect on the blood pressure varies considerably with posture, being minimal when the patient is recumbent and maximal when erect. This has a two-fold disadvantage in that the profound hypotension in the erect posture may of itself produce alarming or inconvenient symptoms, while lack of pressure reduction when recumbent implies uncontrolled hypertension during the hours of sleep. Other factors militating against their successful use are erratic absorption and the development of tolerance, and these have proved serious drawbacks. The erratic absorption of the original hexamethonium compounds, for example, led to serious difficulties, not the least of which was an increased risk of obstinate constipation or actual paralytic ileus since there is a tendency for the unabsorbed drug to accumulate in the gut and then to be absorbed in excessive amounts. With some compounds tolerance is rapidly acquired and continual increases in dose may prove necessary. These- undesirable qualities are most prominent with the quaternary ammonium compounds of which hexamethonium is an example, and less marked with the secondary amines.
Mecamylamine is a member of the latter group and is one of the most dependable of the ganglion-blocking agents. It is completely absorbed and the response to a given dose is relatively constant from day to day. The hypotensive action comes on gradually from one to two hours after ingestion and persists for some six to twelve hours. It is supplied in tablets of 2-5 mg. and 10 mg. for oral administration ; a recommended initial dose is 2-5 mg. twice a day, which may be increased by a daily increment of 2-5 mg. every two or three days until the desired effect on the blood pressure is obtained. As with all members of the group the action is enhanced by the simultaneous adminis¬tration of a thiazide drug, for example 0-5 g. of chlorothiazide or 50 mg. of hydrochlorothiazide twice daily. With such adjuvant therapy the dose of mecamylamine can be considerably reduced, and care must in fact be exercised that over-dosage does not occur. Thiazide drugs also promote potassium loss and it is desirable to give a potassium supplement, say i to 2 g. of potassium chloride daily, as a precaution.
There are many other drugs of this class. The original, hexamethonium tartrate, is absorbed so erratically that its use has been largely abandoned. A later representative, pentolinium tartrate tends to induce tolerance when given orallv, and if injected necessitates repeated doses each day. The drug has largely been superseded by mecamylamine or pempidine which, given orally, are more effective.
Pempidine is claimed to be less toxic and less variable in effect than its precursors. Orally, the initial dose is 2-5 mg. four times per day, increasing by 2-5 mg. each day until a satisfactory reduction in pressure is achieved. Since it is rapidly excreted the therapeutic dosage may be reached with safety in a few days.
Side-effects.—When ganglion-blocking agents are given, the parasympathetic effects may be sufficiently marked to demand symptomatic relief. Constipation is commonlv troublesome and may require the regular administration of aperients. Drvness of the mouth is a nuisance and may to some extent be relieved by mouth washes. If these fail, tablets containing 5 mg. of pilocarpine nitrate may be tried. Paralysis of accommodation can be a considerable handicap, but can be counteracted by the local instillation of eye drops of 0-5 or i per cent. eserine solution or by the wearing of glasses sufficiently strong to compensate for the accommodation defect. Difficulty in micturition, impotence and an undue sensitivity to insulin are other not uncommon side-effects.
Drugs Causing Adrenergic Neurone Paralysis.—The inconvenient and occasionally dangerous side-effects of the ganglion-blocking drugs led to a search for substances which lowered the blood pressure without such disadvantages. From this search there have emerged drugs which act by paralysing the adrenergic neurones without effect on the parsympathetic nervous system. Bretylium tosylate, the first of these drugs was for a time very popular; but while effective in mild cases, it failed to control many severe hypertensions; its absorption and action were erratic; tolerance was rapidly acquired; and side-effects remained troublesome.
Guanethidine has a similar action to bretylium, but differs in its dependable absorption and regular action, while tolerance is seldom acquired. It is slowly excreted and its action is prolonged, lasting at least three days, so that a single daily dose suffices to keep the pressure controlled. It also produces side-effects which on occasion can be troublesome. Prominent among these are diarrhcea, bradycardia, weakness and lassitude with, on occasion, fluid retention to the point of precipitating early cardiac failure. Failure of ejaculation is common. Many patients taking guanethidine develop marked hypotension following muscular exercise, particularly early in the day, and this can lead to syncope. Matutinal weakness may occasionally be so marked that a man cannot shave. through sheer asthenia. The fall in blood pressure with exercise may be remarkable : for example a fall from 220/130 to 90/40 has been recorded. Gross hypotension leading to syncope may also be induced by the vasodilatation produced by a hot bath. Patients should be warned of these hazards and considerable care must be exercised in the use of all such drugs.
A safe initial dose is 10 mg. given in the morning and increments of 10 nag. per day may be made at intervals. The aim is to reduce the standing blood pressure to 160/100 or thereby. The long term maintenance dose to achieve this object varies from 10 to 300 mg. per day, but usually lies in the narrower range of 30 to 120 mg. The smooth stable action and lack of acquired tolerance render it preferable to the older drugs.
Bethanid.ine, chemically akin to bretyllium tosylate and to guanethidine, is a newer drug. Its main advantage over guanethidine is its shorter action, permit¬ting earlier adjustment of dosage. Diarrhoea is a less troublesome side-effect. The initial doseis5mg. orally twice daily, increased at short intervals as necessary up to as much as 50 mg. twice daily.
Another recently introduced drug, methyldopa has proved effective. It inhibits the decarboxylation step in the biosynthesis of nor-adrenaline, and was introduced on this basis to lower arteriolar tonus, but its undoubted hypotensive action is not yet fully explained. It is given orally (0-25 g. tablets) four times daily, the number of tablets being regulated by the response. The daily requirement varies widely up to-two grammes or even more. Side-effects, particularly depression and disturbances of sleep rhythm, are infrequent. The effects on the pressure are comparable to those of guanethidine.
In summary, it may be said that a patient already stabilized on a ganglion-blocking drug with a satisfactory pressure reduction and. without undue parasympathetic side-effects, should be kept on the regimen which has been found to suit him. New patients, however, should probably be tried first on guanethidine, bethanidine or methyldopa which may afford adequate control with minimal side-effects. Nevertheless, if hypotension after exercise or other symptom proves a bar to continued treatment with these, recourse should be had to one of the ganglion-blocking drugs. Among these, mecamylamine and pempidine are the drugs of choice; their action should be enhanced by the simultaneous administration of a thiazide drug. The reserpine group are best reserved for mild cases of hypertension associated with worry or tension, and they may be used as adjuvants to other hypotensive drugs.
Other Hypotensive Drugs.—Chlorothiazide and other thiazides have an effect on hypertension in about one-third of patients, particularly those with milder forms of the disorder. Given as the sole remedy, such drugs are useful in the management of the milder cases, but their main use is as adjuvants to the ganglion-blocking agents, the dosage of which can usually be reduced to one-half if a thiazide is administered simultaneously. Potassium supplements should be given.
Hydrallazine, a potent hypotensive agent, probably acts directly on the peripheral vessels and also increases cardiac output. It has been claimed that renal blood flow is increased, but there is no evidence that glomerular filtration rate is increased or that azotasmia is improved. Because of its renal action its use has been advocated in patients with severe impairment of renal function, but it is relatively little used in this country. Its great disadvantage is that as a long-term side-effect the patient may develop either rheumatic symptoms or a condition closely resembling disseminated lupus erythematosus.
Veratrum alkaloids have the great disadvantage that the therapeutic level is very close to the toxic one, and nausea and vomiting are readily produced by doses little above those required to produce a significant fall in pressure. The dehydrogenated ergot alkaloids (0-5 mg. tablets) have a mild hypotensive action and achieve some reduction in pressure in long-term use.
Combined Treatment.—The simultaneous administration of a thiazide drug with a ganglion-blocking or sympathetic adrenolytic agent strikingly potentiates the activity of the hypotensive drug. Similarly, reserpine may be used as adjuvant therapy and may allow reduction in the daily requirement of the ganglion-blocking or adrenolytic agents. While there is every reason for combining these drugs in an endeavour to find the optimum for the particular patient under treatment, there is some danger in the use of the proprietary mixtures of drugs now on the market. It is highly desirable that the physician should administer each drug in the dosage he finds appropriate to his particular patient, rather than to give them in a set prescription of unvarying proportions at the whim of the manufacturer. Such preparations make elasticity in treatment difficult.
General Considerations in the use of Hypotensive Agents.—Pharma¬cological research has placed in the hands of the doctor potent remedies for the management of hypertension. To realize their full potentialities, however, close attention to the detail of administration is necessary and there is no doubt that today the widespread use of active drugs without adequate supervision is responsible for much inefficient therapy or iatrogenic illness. It is not good therapy, having discovered that a patient has high blood pressure and having decided that he requires treatment, to prescribe a potent hypotensive drug and dismiss him without supervision for several weeks. The institution of treatment with these drugs demands close medical supervision, since patients vary widely in their response to a given dose and a catastrophic fall in pressure may be induced. In sensitive subjects, such untoward complications as myocardial infarction, cerebral thrombosis or renal failure may be precipitated. Again, when a patient has been stabilized on a dose sufficient to control his hypertension, he must be seen at frequent intervals, his pressure checked when recumbent, standing, after exercise, and a watch maintained for undesirable side-effects. Such close supervision is essential because variation of response to hypotensive drugs is so great that no hard and fast schedule of dosage is possible. The initial treatment should be undertaken in hospital, preferably at an out-patient clinic organized for this purpose under the charge of a doctor who is interested in the problems of hypertension and prepared to give time and trouble to the close supervision of individual patients. Treatment of hypertension with these modern drugs can be highly rewarding, but the rewards are bought at the price of hard work and close attention to detail.

HIGH BLOOD PRESSURE

High blood pressure, by reason of its prevalence and the gravity of its sequelae, kills and cripples large numbers of otherwise healthy individuals in the prime of life. It ranks as a major medical problem of the present time. Various potent drugs have been introduced in recent years for its treatment, differing widely in their mode of action and in their sphere of usefulness, so that an already complex subject has become bewildering. For a variety of reasons the full potentialities of the powerful drugs now available are rarely realized in practice, and high blood pressure remains a condition for which only too often little is accomplished in treatment. On the one hand therapy may be prosecuted to the point of harming the patient, while in a large proportion of treated cases the drugs in the dosage given have little effect in sustained control of pressure.
In this as in every other field of medicine adequate therapy must be precedec by accurate diagnosis. It is not sufficient, on demonstrating that a man has a pressure above the average, to label him " high blood pressure " and leave it at that. Diagnosis must be precise, both in respect'of the degree of hypertension and more particularly in regard to its cause.
The degree of hypertension can be assessed by readings of the pressure made under conditions as nearly basal as possible. The patient should be comfortably at rest on a couch in as reaonably warm room and relaxed, so far as may be possible under the conditions of a medical examination. The blood pressure is then taken at intervals during a period of ten or fifteen minutes and the lowest reading is noted as the basal blood pressure. When this is done it will be found that many patients in whom a high initial reading is recorded have, when relaxed, pressures within the accepted normal range. In others, however, the final pressure readings remain above the average, and the questions arise : which figure should be regarded as abnormal and when does an abnormal pressure require treatment.
There is evidence that the height of the blood pressure in the given individual is genetically determined, and like other inherited characteristics such as stature varies over a considerable range in normal individuals. By general agreement the figure of 150/90 mm. Hg. is taken as the upper limit of the normal range at any age. There may be some people whose normal pressure level is above this figure : they are comparable to people who are unusually tall in stature but normal in every other respect. Taking this pressure of 150/90 mm. Hg. as the base line of normality, there is a wide range of variation in the abnormal high pressures encountered. It should be emphasized that the diastolic pressure is of much more diagnostic importance than the systolic pressure. For convenience we may divide those with raised pressures into four broad groups, the pressures quoted below being rough approximations but in no sense accurate limiting factors. The first group—mild hypertensives—have pressures of the order of 160/95 mm. Hg. ; moderate hypertensives have pressures of the order 180/105 mm. Hg. ; severe hypertension is characterized by a pressure around 200/115 mm. Hg. ; and gross hypertension by figures above this level. Into this last group fall the so-called malignant hypertensives in whom the diastolic pressure is 140 or over and in whom papillcedema is a striking and frequent feature, associated commonly with evidence of gross renal, cardiac or cerebral damage. Such classification into rough groups has a bearing on treatment, since in general it is unnecessary and unwise to treat patients with mild or moderate hypertension. Patients with severe hypertension should be treated, particularly when there is evidence of vascular degeneration affecting the vessels of brain, heart, kidney or eye (the target organs), and patients with gross hypertension, particularly those in the malignant phase, are in urgent need of energetic treat¬ment. Such rules are by no means absolute and are modified by such considera¬tions as the age of the patient and evidence of vascular changes in the target organs. For example, a hypertension of the order of 180/105 mm. Hg. in a young person of 30 is much more in need of treatment than a corresponding pressure in a man of 60. And again, when a patient already shows evidence of left ventricular strain and perhaps cardiac asthma as a presenting symptom, therapy is required irrespective of the actual height of his pressure.
Having determined the degree of hypertension, attention should be directed to finding the cause. There are numerous conditions which lead to a secondary rise in blood pressure (secondary hypertension), which must be sought and excluded before the raised pressure in a given patient is classified as primary or essential hypertension. The detailed investigations to be carried out in the search for a cause are beyond the scope of this textbook of treatment.

FOCAL SEPSIS IN RELATION TO HEART DISEASE

The role of focal septic infection in the production of heart disease is uncertain apart from the production of subacute bacterial endocarditis which has been discussed. It is also possible that septic foci may be of astiological importance in some cases with heart block of milder grades and in cases with obstinate extrasystolic irregularities. In such cases, removal of the foci is desirable and is generally without risk if suitable prophylactic measures are taken by pre- and post-operative treatment with penicillin.
The matter is not so simple, however, when symptoms or signs of gall¬bladder disease are found in a patient with heart disease. It is held by some that many patients with cardiac pain and congestive failure may owe their condition to toxaemia from an infected gall-bladder. Others contend that chance association determines the simultaneous occurrence of the two conditions. The subjects of cholecystitis are of the habitus and age in which arterial degeneration and its sequelas of angina and myocardial failure are common. The evidence in favour of the so-called gall-bladder heart is not convincing, and operations for removal of the gall-bladder should be undertaken only when there are clear indications, apart from the cardiac condition, to justify the step. The high mortality attending this operation in patients with hypertension, obesity and impaired myocardial efficiency should be kept in mind.

CIRCULATORY FAILURE IN ACUTE INFECTIONS

In the circulatory failure which occurs in acute infections such as lobar pneumonia, two factors are at work : central, due to failure of the poisoned heart muscle, and peripheral, due to dilatation of the poisoned small vessels. Exhaustion of the adrenals, or their destruction by haemorrhage into their substance as in the Waterhouse-Friderichsen syndrome, plays an important role in the syndrome of toxasmic shock. This peripheral failure is generally more important than central (cardiac) failure. Even in diphtheria, many of the deaths are due to peripheral failure, though in some cases the specific action of the toxin on the heart causes sudden (cardiac) death, often many days after the subsidence of the acute infection.
Once circulatory failure has developed, the prospects of successful treatment are not good. It is then too late for efficient specific therapy, and measures calculated to stimulate the heart or the peripheral vessels are disappointing. The treatment of toxasmic circulatory failure lies in its prevention by early and adequate treatment of the causal infection. In diphtheria, for example, timely administration of antitoxin greatly reduces the incidence of dangerous circu¬latory failure. Similarly in pneumonia, early and efficient specific treatment with antibiotics lessens the risk of later intractable toxsemic effects. In diseases for which no specific treatment exists, or in which failure develops during a long illness, general measures to reduce toxasmia are employed to the best of our ability.
In view of the adrenal factor referred to above, there are logical grounds for using corticosteroids as replacement therapy despite the known disadvantage of their depressant action on the immunity responses of the body. In practice their use has been justified by the results, and hydrocortisone is probably our most potent weapon in combating toxasmic shock. Intramuscular hydrocor¬tisone, o-i to 0-2 g. daily should be given for its depot action, while for its speedy effect the w^ter-soluble hydrocortisone hemisuccinate should be given intravenously. The dosage should be 10 mg. per hour, best given as say i.o mg. added to a pint of dextran infusion fluid, given by drip. An appropriate anti¬biotic should be administered simultaneously in high dosage. While some apparently desperate cases of toxasmic shock in acute infections may be rescued by hydrocortisone, the results of treatment of peripheral failure late in the course of an infection are unsatisfactory. In fact, once such failure has developed,death is likely in spite of all therapy, unless the natural body processes succeed in overcoming the infection, as in the crisis phenomenon of lobar pneumonia. Of drugs which act on the heart, digitalis is the most widely employed : its use in pneumonia, for example, was once traditional, though its value is now discredited. The old controversy as to its value is hardly relevant in these days of efficient antibotics.
Many other drugs enjoyed a reputation as cardiac stimulants, and were widely used in conditions of toxasmic circulatory failure—strychnine and diffusible stimulants. It is now recognized that they have no direct cardiac action and that we do not possess any drug which can whip an exhausted or poisoned heart to renewed activity.

PERICARDITIS

A patient suffering from acute pericarditis, whatever the aetiology, should be nursed at complete rest in bed. For those with acute rheumatic carditis, the general lines of treatment are as described under that heading. In tuberculous cases the general measures are those appropriate to tuberculosis and streptomycin, isoniazid and PAS should be given in appropriate doses. Cases which occur in association with pyogenic infections (haemolytic streptococci, staphylococci, pneumococci, etc.) are treated with the appropriate antibiotic, the possibility of the development of a purulent effusion being kept in mind. The so called benign non-specific variety generally clears up rapidly without specific treatment and without residual disability. Peri¬carditis occurring in the course of disseminated lupus erythematosus responds, like the other manifestations of this protean disorder, to treatment with corticosteroids.
The relief of pain may call for treatment, though many patients suffer surprisingly little discomfort even in the presence of a loud friction rub. Mild analgesics such as acetylsalicyclic acid, or compound codeine tablets may suffice, but severe pain may necessitate the administration of 15 mg. of morphine with the customary proviso regarding its dangers in young children. Counter-irritation and the traditional ice bag have passed into disuse, relief from pain being more easily attained by analgesics.
A large effusion may embarrass the heart's action or interfere with respiration by causing partial collapse of the left lung. It is unusual for such symptoms to be severe enough to warrant aspiration of the pericardial effusion, but tapping must be carried out promptly with the appearance of the signs of tamponade— rising venous pressure and pulse rate, onset of cyanosis, increasing dyspnoea and general distress. Aspiration is also a routine diagnostic procedure when bacterio¬logical examination of the fluid is necessary, or when the presence of pus has to be excluded. For diagnosis the aspiration of a few millilitres of fluid will suffice, but to relieve tamponade the aspiration of several hundred millilitres may be necessary. The technique of paracentesis is described on p. 922. With malig¬nant involvement of the pericardium, rapid re-accumulation of effusion after paracentesis is common ; for this, local radiotherapy may be given by instilling into the sac a radioactive isotope of gold. This is done under the guidance of a radiotherapist, familiar with dosage requirements, isotope hazards to personnel, etc., and is at best palliative.
Pus in the pericardial sac is an indication for surgery. Drainage may be established by open operation, with resection of ribs, or by a closed method, by insertion of a tube through the soft tissue of an interspace and the maintenance of suction. Both methods yield good results, and the choice must lie with the surgeon. Suitable antibiotics should be used systemically and locally.
In non-purulent cases recovery with absorption of the effusion is the rule, except in the terminal acute pericarditis which occurs in the last stages of Bright's disease and other cachectic conditions. Convalescence may be slow, and there is no efficient method of hastening absorption of the fluid. Repeated assessment of the size of the effusion and of the patient's general state will guide the physician in his decision as to when to allow the patient to move about in bed, when to allow him up, etc. Patients on recovery from the acute attack may be allowed a fair amount of exercise, but should be re-examined from time to time during the ensuing years to detect the development of other lesions or of chronic constrictive pericarditis. When pericarditis occurs as part of a polyserositis, joint supervision by physician and thoracic surgeon is desirable, for operation may be indicated at a stage before hard scar tissue or calcined deposits have formed.

SUBACUTE BACTERIAL ENDOCARDITIS

Prior to the discovery of penicillin, subacute bacterial endocarditis was almost invariably fatal ; today, with efficient antibiotic treatment the picture is-entirely different and the majority of those affected may be saved. The mortality, and of almost equal importance the degree of residual disability, depend on two-factors—the stage at which treatment is begun and its thoroughness. If diag¬nosis is delayed for weeks, or months, irreparable damage to a valve may occur, so that even if healing results the heart may be so handicapped that progressive cardiac failure is inevitable. Further, the disease once firmly established becomes more difficult to eradicate. As regards thoroughness of treatment, there is ample evidence that short courses of penicillin for two or three weeks, while yielding a high initial recovery rate, are associated with a considerable relapse rate and a bad overall prognosis.
Early treatment presupposes early diagnosis, and this in turn depends on the diagnostic acumen of the individual doctor. Cases of subacute bacterial endocarditis, like those of every other disease, come first under the observation of the general practitioner, and it is he who should consider this possibility in every case of obscure or unexplained fever occurring in a patient known to suffer from rheumatic or congenital heart disease. The disease may occur with no history or signs of a valvular lesion, especially when the infection has become implanted on a congenital bicuspid aortic valve. A further group of cases is now being diagnosed with increasing frequency, namely in adults over the age of fifty, in whom unhappily the diagnosis is commonly not suspected until the disease is far advanced.
The diagnosis of subacute bacterial endocarditis may be missed in cases of congenital heart disease with a left-to-right shunt (ventricular septal defect, patent ductus arteriosus) since in these emboli are carried not to the systemic circulation but to the lungs, and the characteristic peripheral embolic phenomena so common in the rheumatic case are lacking. Such patients may suffer repeated episodes of respiratory illness, a curious recurrent pneumonic condition, the significance of which may be overlooked. Diagnosis may be further complicated by the injudicious use of penicillin or other antibiotics. These, given in short courses for apparently minor infections, may for a time control fever and inflammation, so that the possibility of subacute bacterial endocarditis may not be considered, and even if it is the diagnosis may be discarded because blood cultures taken after antibiotics have been given are likely to be negative.
When a doctor suspects subacute bacterial endocarditis on clinical grounds ever}7 attempt should be made to isolate the organism. Repeated blood cultures should be undertaken, and a higher percentage of positive results will be obtained if these are done in series of three on any one day. A spike of temperature should suggest the withdrawal of blood for culture on three occasions at hourly or two-hourly intervals, and this process should be repeated on successive days till four or five batches have been sent for examination. No antibiotics should be
•administered until such tests have been carried out, but treatment should be started without delay as soon as the cultures have been taken.
The isolation of the organism and the determination of its sensitivity to penicillin and other antibiotics decide both the choice and the dose of antibiotic to be given. Not all cases are due to the Streptococcus viridans, a proportion being due to other organisms varying widely in resistance to penicillin. This is particularly true of S. fixcalis, a commonly highly resistant organism which
•may gain access to the blood stream from the urinary tract. In a proportion of patients no organism is isolated from the blood and a significant number of abacterial cases occur even when investigations are carefully carried out. The incidence is reduced if blood cultures are made sufficiently frequently and with
•appropriate techniques. These abacterial cases should not be denied vigorous treatment as soon as a number of blood cultures have been made.

Choice of Antibiotic, Dosage and Duration of Treatment.—For the average case from which a fully sensitive S. viridans has been isolated the standard course of treatment consists of the intramuscular injection of 5 million units of penicillin daily in divided doses, continued over a period of fifty-six days. It may seem cruel to inflict four or five painful needle pricks daily over a period of eight weeks, particularly to a child, but the author has still to be convinced that procaine penicillin or oral preparations of penicillin are equally effective ; the disease is of such gravity that it is imperative to pursue treatment in the most effective fashion. When the organism recovered is more resistant than usual this dosage may have to be increased even up to 20 million units daily, and an adjuvant antibiotic added, for which purpose streptomycin, i g. daily by intra¬muscular injection, is usually the drug of choice. The broad-spectrum oral antibiotics of the tetracycline group are not of great value in treatment of subacute bacterial endocarditis, though on occasion an organism may be recovered which is sensitive to one member of the group and resistant to penicillin or streptomycin. When a very high blood level of penicillin is desired the renal tubular-blocking action of probenecid (p. 59) may be employed. The desired result is achieved without greatly increasing the dose of antibiotic.
General Treatment.—The general treatment of a patient with subacute bacterial endocarditis is that for any febrile infective illness, modified by the severity of the cardiac lesions present. In the patient whose valves are so grossly damaged and whose heart muscle is so poisoned by toxeemia that he is in cardiac failure, complete rest and treatment along standard lines for congestive heart failure will be required for weeks or months. Angemia and malnutrition must be treated appropriately. Those patients in whom the infection has been diagnosed and treated at an early stage, and in whom cardiac enlargement and valve damage are minimal and failure absent, need only be kept in bed for two to three weeks, after w^hich a progressive increase in activity may be allowed.
Embolism.—Major embolic accidents, affecting the cerebral circulation or other important systemic arteries, are frequent and account for a considerable proportion of fatalities. Such accidents are unfortunately not reduced by anti-coagulants which have no place in the treatment of this disease. Death from embolism is most likely to occur in patients with large crumbling vegetations— that is in patients who have suffered from the disease for a considerable period before a correct diagnosis has been made and treatment commenced. The over¬all mortality from these embolic accidents is of the order of 10 per cent.
Prophylaxis—Septic Foci.—Every patient with known rheumatic or congenital heart disease should be subjected to regular dental survey so that early sepsis can be detected and dealt with. No such patient should be permitted to have a dead crowned tooth, since apical infection in such a case is probable and may escape notice since it may be painless. Dental extractions should always be carried out under protection with soluble penicillin administered by injection an hour or two before and for two or three days after the dental operation. Similarly, infections of the urinary tract in such individuals should be efficiently treated, since it is known that S. fcecalis may gain entry to the blood stream from such a focus. Patients under treatment for subacute bacterial endocarditis should also be carefully investigated for septic foci and if these are found they should be dealt with while the patient is under the protection of an antibiotic. Failure to eliminate a septic focus may lead to repeated re-infection and relapse of the endocarditis.
Prognosis.—Even with efficient treatment the prognosis varies considerably with the stage at which treatment is begun. The overall recovery rate today is of the order of 75 per cent. Patients diagnosed and treated at a late stage and who may already be in cardiac failure, have a much worse prognosis, the recovery rate being 50 per cent. or less, and the survivors tend to lapse at an early date into cardiac failure. When patients are treated at an early stage the recovery rate is of the order of 90 per cent. and residual disability may be slight. It cannot be too strongly emphasized that to obtain the best results early diagnosis and efficient treatment are imperative.

RHEUMATIC CARDITIS AND RHEUMATIC FEVER

The incidence of acute rhematic fever has fallen dramatically in this country over the last 20 years, a fortunate circumstance, since treatment remains unsatisfactory. Sulphonamides, penicillin and corticosteroids have all in turn been found in greater or less degree disappointing. Rest in bed and the administration of sodium salicylate or soluble aspirin remain, at least in domicil¬iary practice, the mainstays of treatment.

Penicillin.—While penicillin is without action on the course of rheumatic fever or carditis, it is used in treatment to eliminate persistent (tonsillar) streptococcal infection and to prevent re-infection. A week's intensive course of soluble penicillin is given at the outset followed throughout the patient's stay in hospital and after discharge with phenoxymethylpenicillin by mouth. Such treatment is given along with salicylate or other anti-rheumatic drug.

Corticosteroids.—In some patients with severe pancarditis in whom the administration of salicylates pushed to toxic limits have failed, corticosteroids have produced dramatic improvement, leading not only to disappearance of fever and arthritis but to rapid resolution of the cardiac affection, improvements which have been maintained. In others, however, the hormones have failed to influence the condition, and there seems to be no means of predicting which patients will respond and which will not. On occasion, however, corticosteroids produce effects of an altogether different order from those of other lines of treatment. Prednisolone is preferable to cortisone, since its salt-retaining action is less marked. The other recognized side-effects have not proved troublesome in the relatively short courses required in acute carditis. It is well to reserve its use for acute cases under institutional care.

Rest.—The child who develops acute or subacute rheumatism should be confined to bed till all the signs of rheumatic activity have subsided. Good nursing is essential, and during an. active carditis the patient should not be allowed to do anything for himself. The achievement of complete physical rest in young children without acute symptoms may present difficulty, but confine¬ment to bed should be maintained even although the child is moving about freely in bed, for to allow such a child up greatly increases the demands made on the heart and circulation. During the period of fever, with its accompanying profuse perspiration, careful toilet of the skin is necessary and will lessen the risk of sweat rashes. The diet should be fluid and light, as for any other febrile condition. The duration of bed rest is discussed below.

Salicylates.—Salicylate has generally been regarded as being without action on the progress of the carditis, though exerting a striking and specific effect on the fever and arthritis. Recent work, however, suggests that it may produce similar effects to cortisone and corticotrophin through the pituitary-adrenal system. There is evidence that when the blood salicylate level is kept steadily between 30 and 40 mg. per 100 ml., not only are the fever and arthritis abolished but the E.S.R. returns more quickly to normal and the duration of the disease is shortened.
If the condition is to be treated in domiciliary practice without biochemical control the drug must be given in doses sufficient to produce the symptoms of mild salicylate intoxication. So-called drug resistance is in many cases due to under-dosage. The daily dose required varies with the age and weight of the patient. The guide to the dose in any individual case is clinical: the abolition of joint pains and of pyrexia, or the development of mild symptoms of salicism (deafness, tinnitus, etc.). In general, for an adult, doses of 1-5 to 2 g. (20 to 30 gr.) two- or three-hourly will be required, a total of 12 g. (200 gr.) per day being commonly sufficient. In children the effective daily dose varies from 4 to 8 g. (60 to 120 gr.) per day, according to age. The old practice of giving sodium salicylate with bicarbonate simply enhances excretion, and necessitates giving about twice the amount of salicylate to produce a given effect. Such doses may produce gastric irritation, and this may be the limiting factor in dosage. When sodium salicylate is badly tolerated, aspirin, or, better, soluble aspirin, may be substituted. The latter is prescribed as tablets to be dissolved in cold water immediately before use. Dosage again has to be pushed so far as the tolerance of the patient permits. The intravenous administration of salicylate has not been shown to possess appreciable advantages over oral administration and the risk of toxic reactions is much increased.
Once fever and pain have subsided, or when symptoms of salicism have appeared, the dosage of salicylate should be reduced. This can generally be done within a few days from the start of treatment. The drug should not, however, be entirely discontinued, but should be administered in smaller doses so long as the rheumatic process remains active. The maintenance dose is that which will just suffice to keep pain and fever in abeyance, and for an adult is generally from 6 to 7 g. (100 to 120 gr.) per day. Recurrence of acute symptoms is common when the maintenance dose is reduced as low as 4 g. (60 gr.) per day. Should such recurrence occur, the dose must be temporarily increased.

Local Treatment for the affected joints should be simple. Wrapping in cottonwool and bandaging to secure rest generally suffice during the few days of acute pain. The application of liniments is valueless. Care is essential in patients in whom pain lasts more than a few days, since, contrary to general teaching, permanent joint affection may result from rheumatic fever. This rare complication is seen now and then in adolescent patients in whom unequivocal carditis has been associated with arthritis of small joints of hands and mandible, and in whom lasting deformity has resulted. Continuous immobilization of joints always carries the risk of later limitation of movement. Therefore passive movement through the maximum range, short of causing pain, should be performed daily as soon as the most acute symptoms subside, and immobilization during the rest of the day should be in the best orthopzedic position.
Focal Sepsis.—In many cases of rheumatic fever a focus of streptococcal infection in tonsils or upper respiratory tract remains active throughout the course of the disease. Penicillin, used as suggested above, has rendered it rare nowadays for the physician to be faced with the serious decision of advising tonsillectomy at the risk of provoking a severe and possibly fatal exacerbation. The risk is such that every effort should be made to eradicate streptococci by anti¬biotics rather than hazard tonsillectomy. Cover by antibiotics should be given before operations on teeth or tonsils in apparently quiescent rheumatic cases.
Routine tonsillectomy of healthy children does not protect them against subsequent attacks of rheumatic fever, nor after a first attack does it appreciably lessen the risk of recurrence of rheumatism. It is wise to advise tonsillectomy" only when the local condition is such as would demand operation in a non-rheumatic case, to choose the time for operation with great care and to secure antibiotic cover Duration of Rest.—The question of how long a patient with rheumatic: carditis is to be kept in bed is not easily answered. No hard-and-fast rule cani be laid down, though many advocate a minimum of three months' rest in bed;
after even a mild attack. Certainly one encounters with distressing frequency patients with established valvular disease who give a history of arthritis treated by a short period of rest followed by a quick return to normal activity. On the other hand, in fully one-third of all cases with symptoms of the effort syndrome admitted to an army centre for rehabilitation, the onset of the symptoms and of the disability could be traced to a doctor's warning to parents or patient that strenuous activity must be avoided. It is true that in all cases with clinical evidence of active carditis, rest in bed should be prolonged so long as the signs of activity persist, and this may extend over a period of many months. It is wrong, however, to prolong rest after signs of activity have disappeared. Not only is an established, static valvular lesion not benefited by such treatment, but there is evidence that moderate exercise is beneficial for the subjects of early valvular disease.
The criteria for determining quiescence of carditis must, therefore, be con¬sidered. A smouldering valvulitis of sufficient intensity to produce eventual gross fibrosis may go on for many months, and yet with very little clinical upset. The pulse rate and temperature may be normal and cardiac enlargement absent even though active infection persists in the valves. Sinus arrhythmia is not a safe indication that the heart has escaped damage, and the duration or degree of joint involvement bears no relation to the extent of the cardiac lesions. Sub¬cutaneous nodules when present indicate persistent rheumatic activity, but their absence does not exclude active carditis. Electrocardiographic changes (pro¬longed P-R interval, prolongation of the duration of QRST beyond the calculated normal for the heart rate and T-wave inversions) when present are indicative of active myocarditis. The return of the blood sedimentation rate (E.S.R.) to normal is generally a guide to the cessation of activity, but is not infallible. It may be normal in the presence of congestive failure, but such cases are easily recognized, and the question of allowing the patient up does not arise. Now and then a normal E.S.R. persists in a patient showing no signs of failure while other evidence of carditis is obvious. Conversely, a raised E.S.R. does not necessarily indicate carditis, for many conditions increase it. By careful clinical examination the true significance of the E.S.R. can usually be assessed. Other criteria of cessation of activity are gain in weight in children if not due to oedema, stabilization of the position of the apex beat and of physical signs in the heart, and a stable pulse rate, particularly during sleep.
Children who have suffered from repeated attacks of carditis may develop a severe and occasionally fatal acute pancarditis. The handling of such a case can be as sad a task as any that a doctor has to face; ordinary measures fail to arrest or retard the disease, and treatment is symptomatic. In such fulminating cases corticosteroids have on occasion proved valuable, but in a proportion these drugs, too, fail to stay the course of the disease.
Convalescence.—When the period of complete rest in bed is over, the return to activity should be gradual and carefully supervised. Any recrudescence •of the rheumatic process should be met by a prompt return to complete rest.
The child who has weathered rheumatic carditis is frequently sent for a :short period to a convalescent home, and then returns to school and to full routine. This is unsatisfactory, and is probably responsible for much later disability. Convalescence should be protracted, and after the period in hospital the child should be sent to a convalescent home. In some parts of the country special homes have been established where adequate medical attention and supervision are available in healthy surroundings.
After-Care.—On discharge from such an institution/or after convales¬cence at home, the child should return gradually to activity, the limitation of effort being determined by the extent of the cardiac damage. In cases with mild but quiescent valvular lesions full activity is allowable with a prohibition only on such strenuous exertions as competitive sports. A patient with gross myocardial damage and hypertrophy must, however, lead a quiet, sedentary life. Careful follow-up with periodic assessment of general health and cardiac condition is essential, and any sign of renewed rheumatic activity demands prompt measures—rest in bed, etc. It is understandable that such solicitous after-care may well engender a cardiac neurosis—a point always to be borne in mind.
The prevention of recurrent streptococcal infection is important, by the long-continued administration of penicillin either by the weekly injection of 1,000,000 units of a long-acting preparation (benzathine penicillin, B.P.) or the oral administration of 250 mg. of phenoxymethyl penicillin twice daily.
The choice of a future occupation should always be made under the guidance of the doctor. Instances of young adults with advanced cardiac lesions engaged in strenuous occupations are all too familiar, and would not occur if after care were efficient. It is vital that the education of a child should not be neglected during long periods of semi-invalidism. Many rheumatic children leave school at sixteen years with much less than average schooling and are driven on to the unskilled labour market. Better education means greater ability to secure a sedentary occupation which will not lead so soon to a cardiac breakdown. There is ample scope for the doctor, in village or city, to make himself acquainted with local industries, and by direct approach to employers to secure the right niche for the individual patient. Light, skilled crafts (wood- and leather-work; radio mechanics ; precision instrument making, watchmaking, etc.) are remunerative, make little call on physical strength and maintain the patient's interest and independence. Often the journey to and from work or school, and the exposure to inclement weather involved, impose greater strain and risk of relapse than the actual physical strain of employment,
It is implicit that diagnosis must be accurate. Far too many children are lightly diagnosed as suffering from valvular disease on the basis of a systolic or exocardial murmur unaccompanied by cardiac enlargement, and it is fair to say that for one young adult with a mitral stenosis that has been missed by his doctor one sees several with innocent murmurs labelled organic. When such important matters are involved as the whole future of a young patient, his choice of vocation or her fitness for marriage and child-bearing, it is surely incumbent on the doctor to exercise the greatest care. As diagnosis is admittedly often difficult, the doctor should seek specialist and radiological help before pro¬nouncing an opinion. A thoughtless remark after a superficial examination may have disastrous consequences.