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CARDIOVASCULAR SYPHILIS
[JULY 1, 1933
ADDRESSES AND ORIGINAL ARTICLES CARDIOVASCULAR SYPHILIS BY E. NOBLE
*
CHAMBERLAIN, M.D., M.SC. LIVERP., M.R.C.P. LOND.
ASSISTANT PHYSICIAN AND SENIOR CARDIOLOGIST, ROYAL LECTURER ON SOUTHERN HOSPITAL, LIVERPOOL; PHYSIOLOGY IN THE UNIVERSITY OF LIVERPOOL
IT is not the purpose of this paper to deal with the pathological aspects of cardiovascular syphilis, but rather to emphasise the clinical features of a protean disease. This may, perhaps, best be secured by describing separately the recognised types. Aortitis as the precursor of aneurysm and of syphilitic aortic regurgitation is of paramount importance, and its early recognition might do much to avoid its serious sequelse. Yet when we inquire how such a diagnosis may be made we are confronted with great but not unexpected difficulties, for the microscopical changes are well advanced before any detectable anatomical disturbances take place. Certain symptoms and signs, however, when found in combination may be sufficient to warrant a diagnosis. In the absence of gross arterio-sclerosis and arterial hypertension, accentuation of and particularly a metallic ringing quality of the second aortic sound is often regarded as a suggestive sign, though it is so common in persons over 50 that due care must be taken in appraising its value as a sign of aortitis. By contrast, a diminution in the intensity of the second aortic sound may be an early indication of an aortic leak, though such a diagnosis cannot, of course, be established on this sign alone. Systolic murmurs over the aortic area are of doubtful significance, but some regard them as significant when found in conjunction with other signs of aortitis. Possibly percussion may reveal a little increase in the aortic dullness. These signs may be accompanied by symptoms such as painB and breathlessness, and the latter is often nocturnal. It is natural that as the diagnosis rests on such equivocal signs as these, some more decisive method should be
sought. Radiological examinations, both by teleradiogram and screening, have been found of considerable service in skilled hands, though diagnosis of aortitis with X rays is not possible unless other physical signs support it. Thus, whilst Kurtz and Eyster1 found fluoroscopic evidence of aortitis in 90 per cent. of2 cases of acquired syphilis, Ingraham and Maynard found no such evidence in early syphilis, and Bach and Worster-Drought3 in only 2 out of 25 cases of neurosyphilis. The radiological criteria of a pathological aorta as given by David Steel4 are as follows: (1) a dense shadow with a hazy border; (2) a high, dense, prominent aortic knob ; (3) irregular and also general dilatation-the most important sign ; (4) increased pulsation. Other writers in general agree with this statement, but much difference of opinion exists to the accuracy of
as
based upon radiological methods. All are agreed that the facts must be pieced carefully together, and may under certain circumstances justify a grave suspicion of aortitis. Even then the specific nature of the lesion does not follow, and arterio-sclerotic forms of aortitis may be mistaken for those due to syphilis.
diagnosis
* A paper read before the March 16th, 1933. 5731
5731
Liverpool Medical Institution,
In making a differential diagnosis, a positive Wassermann reaction is of moment and may be called forth by a provocative dose of organic arsenic, but is by no means conclusive of the syphilitic nature of the disease. Search should be made for other signs of syphilis, for example, of the nervous system or viscera, and the past history of the patient must be considered. Any suspicion of aneurysmal dilatation is much in favour of syphilis, whilst aortic leakage in the absence of a rheumatic history and particularly in persons over 35 is nearly always syphilitic. Aneurysm, the direct sequel of aortitis, needs little discussion in this paper, for its diagnosis is sufficiently familiar and its syphilitic origin universally admitted. AORTIC REGURGITATION
Another
of syphilitic aortitis deserves of the occasional difficulty in separating syphilitic cases from those due to rheumatism and other causes. Aortic leakage is sometimes found in old age associated with arterio-sclerotic dilatation of the aorta, but cases of this type are rare and can be dismissed here. Another cause of aortic incompetence sometimes overlooked in differential diagnosis is infective endocarditis, especially in its subacute form. If systematic search is made in all valvular lesions for pyrexia, enlargement of the spleen, petechiæ, clubbing of the fingers, hsematuria, and other signs of systemic infection this possibility will not escape the observer. Rupture of the aortic cusps is an unusual cause of incompetence with a characteristic history of severe trauma. When these rare causes have been excluded the diagnosis as a rule rests between aortic regurgitation of rheumatic and of syphilitic origin. In distinguishing these, age is of first importance--the rheumatic type generally occurring in children and young adults, the syphilitic in middle age. Rheumatic cases may not, of course, be recognised until mid-life, especially when the damage to the valves has been limited and non-progressive. The history, though at times conclusive, is frequently of little value, for it is well known that mild forms of rheumatism may escape notice, while a history of syphilis is often concealed. The coincidence of mitral valve defects is generally in favour of a rheumatic origin for the aortic disease, but the presence of an Austin Flint presystolic murmur at the mitral area may lead to difficulty. Clinical or radiological evidence of enlargement of the left auricle suggests mitral disease, as may right ventricular preponderance and increase in the amplitude and duration of the P-waves in the
sequel
attention in view
electrocardiogram. MYOCARDIAL LESIONS
.
The frequency with which syphilis attacks the myocardium is much in dispute. On clinical grounds the diagnosis of syphilitic myocarditis has always proved difficult, and certain pathologists claim that it occurs with much greater frequency than would 5
Warthin appear from observations in the wards. in particular emphasised its great frequency. He found what he considered to be evidence of syphilitic myocarditis, sometimes slight, sometimes great, in every male patient with latent syphilis. In females the incidence was much less. Warthin described microscopic features which he considered pathognomonic of syphilitic myocarditis, and in many cases was able to demonstrate the presence of spirochætes. His views, therefore, cannot be dismissed lightly. A
2
Unfortunately, however, other investigators have been unable to confirm his observations. Clawson and Bell,6 for example, after examining 126 cases of syphilitic aortitis, found that the myocardial changes were such that in most cases they could be accounted for by a mild non-specific coronary disease. Again, Martlandstates that specific lesions of the myocardium and of the coronary arteries beyond the aortic wall are infrequent and usually so slight as to be unimportant. In spite of these conflicting statements, the majority of workers would agree that myocardial involvement is by no means rare in cardiovascular syphilis. Such involvement might be brought about by direct invasion of the myocardium with the Spirochmta pallida or its toxins, at a stage of the disease which will be discussed subsequently, or it might be due to specific changes in the coronary arteries due to extension from a syphilitic aorta. Coronary disease of this kind would inevitably impair the blood-supply to the myocardium. In establishing a diagnosis of syphilitic myocarditis no single physical sign must be given undue prominence. This platitude deserves emphasis in all types of myocardial lesion. Some authorities consider that idiopathic hypertrophy of the heart (Carter and Baker 8; Martland 7) is suggestive of a syphilitic origin, and most would agree that when the hypertrophy is found without valvular disease, arterial hypertension, or arterio-sclerosis, syphilis should be considered seriously as the cause. Especially is this the case in middle-aged persons in whom a rheumatic origin is unlikely. In a series of 232 cases of syphilis examined by Chamberlain and Follows, 11 were found by palpation and percussion to have cardiac hypertrophy with no other abnormal signs, and several of these were young persons. The symptomatology of syphilitic myocarditis is not pathognomonic; breathlessness, palpitations, precordial pain, and other features being common to all types of myocardial lesions. Some have stressed the occurrence of breathlessness and pain at night, but I have been unable to satisfy myself that this is a genuine point of difference between syphilitic and other heart lesions. On the other hand, certain negative features may prove of value in distinguishing syphilitic from other forms of myocardial lesion. Auricular fibrillation or other irregularities rarely occur as a result of syphilis. Coronary infarction is more frequently associated with arterio-sclerotic than with syphilitic changes in the coronary arteries, and its occurrence is against a diagnosis of syphilis. The Wassermann test is, of course, most necessary and very valuable if allowance is made for the high incidence of a positive reaction amongst a population who may develop heart disease of non-specific origin. Moreover, true cases of cardiovascular syphilis undoubtedly occur with a negative Wassermann reaction. In the latter group, a provocative dose of neokharsivan may produce a conclusive response. Finally, the electrocardiograph may assist in the diagnosis of myocarditis, but does not (as stated by some workers) give any clue to the syphilitic nature of the disease. The electrocardiogram may reveal unsuspected myocardial disease by the presence of abnormal T-waves, bundle-branch block, and delayed conductivity in the bundle of His. In the 232 cases examined by Chamberlain and Follows, of whom 221 were electrocardiographed, gross electrocardiographic defects were found in six cases, and minor but suspicious defects in a further seven. These results included cases of T-wave negativity and partial bundle-branch block, and with a few exceptions there
no clinical evidence of cardiovascular disease. Clinical defects without electrocardiographic abnormality were present in the 11 cases .of cardiac hypertrophy previously mentioned, and in three cases of aortic regurgitation, two of whom showed a normal electrocardiogram. The results of the investigation emphasise the importance of combined clinical and
was
electrocardiographic this type.
examination in
investigations
of
STAGE OF INVASION IN CARDIAC SYPHILIS
The view of Warthin, that the spirochæte invades the myocardium and aorta during the stage of bacteræmia—i.e., in the secondary stage of syphiliswould lead one to expect changes in the heart and aorta in this phase of the disease, for the spiroch2ate is capable of producing an intense reaction in the tissues it invades. Yet the number of recorded cases of cardiovascular disease in the secondary stage is small, and many authorities cast doubt upon them. The general consensus of opinion supports the view that after the secondary stage the spirochaete lies latent in the body for 15-25 years before attacking the cardiovascular and other tissues. In this dormant period little is known of its activities, but there is much to suggest that its resting place is in the mediastinal glands, from which at a favourable time it may gain ready access to the heart and aorta. This "
lymphogenous " theory
was
convincingly put
forward by Carey Coombs9 and was based on the observations of Klotz/" Martland,7 and others. Whilst common experience dictates that heart disease does not occur until 15-25 years after the primary syphilitic infection, there are undoubtedly many cases which arise within a shorter interval. The recognition of these is of great importance, for in younger persons their course may be more rapid but more amenable to treatment. For their detection all methods of examination-clinical, electrocardiographic, and radiological-may be necessary. COURSE AND TREATMENT OF CARDIAC SYPHILIS
The outlook in clinically recognisable cardiovascular syphilis is unfavourable, most cases following a progressively downward course. Willius 11 found that the duration of cases of syphilitic aortitis and aortic regurgitation averaged 23 years from the occurrence of primary syphilis, aneurysm averaging 26 years. The greater part of this period would be occupied by the so-called " latent " period, in which no symptoms are manifest and in which the disease is usually undetectable. In some cases the electrocardiograph or X ray might demonstrate suspicious changes while the patient was still symptomless, and in this type of case a repetition of antisyphilitic treatment might stay the advance of the visceral changes. Even when cardiovascular syphilis is clinically
apparent, a course of suitable treatment may modify gloomy prognosis. The work of Moore and Danglade 12 suggests that life may be prolonged from 9 to 69 months in aneurysm, and in aortic regurgita-
the
tion from 32 to 65 months. The manner in which death is brought about by cardiovascular syphilis is variable and presents few characteristic features. In aortic regurgitation death may occur from gradual congestive heart failure or suddenly from defective filling of the coronary vessels. Syphilitic heart disease as a cause of sudden death is emphasised on clinical grounds by Martland7 and on pathological grounds by Warthin.13 The latter states that " it occurred five times more frequently in syphilitic than in non-syphilitic autopsies."
3 The treatment of cardiovascular syphilis has always been a vexed problem. Some have advocated heroic antisyphilitic measures irrespective of the type and grade of the cardiac lesion ; others have held with depressing fatalism that treatment has no effect whatsoever. Even of the time-honoured administration of iodides a German cynic writes : Wenn mann nicht weiss wo, wann, Denn gibt man Iodkalium."
warum
The indiscriminate treatment of all cases of cardiac syphilis, especially with arsenicals, cannot be too strongly condemned. It is well known that an aggravation of local symptoms, called the Herxheimer reaction, may take place after intensive administration of antisyphilitic remedies, especially arsenic preparations, but may be prevented by careful alternation between heavy metals-i.e., mercury or bismuth, and arsenicals. Similarly a therapeutic paradox has been described by Wile 14 relating specially to the cardioIn this there is a remarkable vascular system. improvement in the patient’s general condition after the administration of arsenicals, shortly followed by aggravation of the local cardiac symptoms. The explanation of this phenomenon is uncertain, but it has been suggested that the syphilitic products may be too rapidly replaced by scar tissue, or that their disintegration produces chemical substances with a deleterious influence on the local lesion. If accidents in therapy are to be eliminated cases must be selected with care, and treatment must be cautious. With these reservations there is every reason to believe that treatment may be of value not only in relief of symptoms but in the prolongation of life. In choosing suitable cases, one of the guiding principles should be the state of the cardiac reserve. Cases of decompensation with cedema, enlarged liver, or other congestive signs require restoration of compensation by the usual remedies, such as digitalis and rest, before any antispecific treatment can be carried out with safety. When compensation is good or has been restored by treatment, the patient may commence antisyphilitic measures. A good rule is to begin with iodides and mercury or bismuth, and note the response before using arsenic. Treatment with iodides and the heavy metals may be continued for 6-12 weeks before any arsenic is given. Although it is difficult, without a large number of cases, to compare the effects of one drug with another, I have gained the general impression that bismuth gives better results than mercury in cardiovascular syphilis, especially when pain is a prominent symptom. It may be given in initial doses of 0-1 g., usually contained in 0-5 c.cm. of one of the suspended preparations, such as Bismostab, and the dose increased to 0-2 g. after three or four weeks. Six to eight weekly injections should be given. If the patient shows sufficient response to these lines of treatment, small doses of arsenic may next be given. Various preparations are recommended. Kharsulphan and Neokharsivan are reliable preparations, but should be given in small initial doses, say of 0-1 g., and gradually increased over a course of ten to twelve weeks. American workers recommend Neoarsphenamine or Bismarsen in similar doses. In aortitis the same principles may be adoptedviz., preliminary iodides and a heavy metal, followed by cautious arsenic administration, but here the preparation of most value appears to be Tryparsamide, given in doses of 0-5 g. increasing to 1-0 g. Adverse symptoms such as the Herxheimer reaction and Wile’s therapeutic paradox are indications for the
discontinuance of arsenicals and reliance must then be placed on careful use of bismuth and iodides. It is still uncertain whether specific measures prevent the progress of early syphilitic lesions such as aortitis and myocarditis, but as there is some evidence in favour of this it seems only right that the patient should have the benefit of full treatment, repeated at necessary intervals. When gross structural changes have occurred, as in aneurysm or grave aortic incompetence, the most that can be hoped for is arrest in the progress of the disease and relief of symptoms, and these cases above all require careful handling, usually responding better to iodides and bismuth than to arsenicals. If there is a probability of gummatous collections in the heart, involving, for example, the bundle of His or its branches, fuller doses of iodides-grs. 60-120 daily-may be worth a trial. It is well known that large doses of iodides are also of value in relieving the pain of syphilitic aortitis and aneurysm. Arsenicals should be prohibited in advanced cases of aortic disease and aneurysm, and in patients showing evidence of serious coronary disease generally detected by electrocardiographic means. Bismuth, mercury, and iodides are rarely dangerous, but even they require gentle administration, and should be discontinued if the results are obviously adverse. In conclusion, I should like to express my thanks to Dr. A. A. Fitch and Dr. A. 0. F. Ross, who have .given me free access to their clinics and much
valuable
help. REFERENCES
1. Kurtz, C. M., and Eyster, J. A. E. : Amer. Heart Jour., 1930, vi., 67. 2. Ingraham, R., and Maynard, E. P. : Ibid., p. 82. 3. Bach, F., and Worster-Drought, C.: THE LANCET, 1930, ii., 1113. 4. Steel, David: Amer. Heart Jour., 1930, vi., 59. 5. Warthin, A. S.: Brit, Med. Jour., 1929, ii., 236. 6. Clawson, B. J., and Bell, E. T. : Arch. Path. and Lab. Med., 1927, iv., 922. 7. Martland, H. S.: Amer. Heart Jour., 1930, vi., 1. 8. Carter, E. P., and Baker, B. M.: Bull. Johns Hopkins Hosp., 1931, xlviii., 315. 9. Coombs, Carey F. : Quart. Jour. Med., 1932, xxxv., 179. 10. Klotz, O. : Amer. Jour. Med. Sci., 1918, civ., 92. 11. Willius, F. A.: Amer. Heart Jour., 1930-31, vi., 113. 12. Moore, J. E., and Danglade, J. H. : Ibid., p. 148. 13. Warthin, A. S. : Ibid., p. 163. 14. Wile, W. J. : Ibid., p. 157.
DEVELOPMENTS
AT
HARROGATE.—On
Saturday,
June 17th, Lord Horder opened the new sun colonnade which is the latest amenity at Harrogate. Speaking of British health resorts in general, he said that" we are only now beginning to appreciate the possibilities offered by the medicinal waters of our own country," but " in the matter of spa treatment, at any rate, the facilities at our disposal are as good in Great Britain as they are abroad." Given the energetic and intelligent cooperation of the doctors, the municipal authorities, and the town, he said, there was no reason whatever why British spas should not be as successful and as popular as their continental rivals. But success here, as in all other matters, presupposed courage, foresight, and intelligence. The people of Harrogate had been wise, he thought, in their latest attempt to bring the human gifts of design and adaptation to bear upon natural beauty, and the new promenade was only the first part of a large and necessary scheme to improve the facilities offered. The colonnade or sun walk is 600 feet long, is roofed with vita glass, and broadens into bays at two points, terminating in a cafe and concert hall. The next part of the scheme is the erection of a new pump-room, whose eventual cost will be jE60,000.
ADDRESSES AND ORIGINAL ARTICLES CARDIOVASCULAR SYPHILIS BY E. NOBLE
*
CHAMBERLAIN, M.D., M.SC. LIVERP., M.R.C.P. LOND.
ASSISTANT PHYSICIAN AND SENIOR CARDIOLOGIST, ROYAL LECTURER ON SOUTHERN HOSPITAL, LIVERPOOL; PHYSIOLOGY IN THE UNIVERSITY OF LIVERPOOL
IT is not the purpose of this paper to deal with the pathological aspects of cardiovascular syphilis, but rather to emphasise the clinical features of a protean disease. This may, perhaps, best be secured by describing separately the recognised types. Aortitis as the precursor of aneurysm and of syphilitic aortic regurgitation is of paramount importance, and its early recognition might do much to avoid its serious sequelse. Yet when we inquire how such a diagnosis may be made we are confronted with great but not unexpected difficulties, for the microscopical changes are well advanced before any detectable anatomical disturbances take place. Certain symptoms and signs, however, when found in combination may be sufficient to warrant a diagnosis. In the absence of gross arterio-sclerosis and arterial hypertension, accentuation of and particularly a metallic ringing quality of the second aortic sound is often regarded as a suggestive sign, though it is so common in persons over 50 that due care must be taken in appraising its value as a sign of aortitis. By contrast, a diminution in the intensity of the second aortic sound may be an early indication of an aortic leak, though such a diagnosis cannot, of course, be established on this sign alone. Systolic murmurs over the aortic area are of doubtful significance, but some regard them as significant when found in conjunction with other signs of aortitis. Possibly percussion may reveal a little increase in the aortic dullness. These signs may be accompanied by symptoms such as painB and breathlessness, and the latter is often nocturnal. It is natural that as the diagnosis rests on such equivocal signs as these, some more decisive method should be
sought. Radiological examinations, both by teleradiogram and screening, have been found of considerable service in skilled hands, though diagnosis of aortitis with X rays is not possible unless other physical signs support it. Thus, whilst Kurtz and Eyster1 found fluoroscopic evidence of aortitis in 90 per cent. of2 cases of acquired syphilis, Ingraham and Maynard found no such evidence in early syphilis, and Bach and Worster-Drought3 in only 2 out of 25 cases of neurosyphilis. The radiological criteria of a pathological aorta as given by David Steel4 are as follows: (1) a dense shadow with a hazy border; (2) a high, dense, prominent aortic knob ; (3) irregular and also general dilatation-the most important sign ; (4) increased pulsation. Other writers in general agree with this statement, but much difference of opinion exists to the accuracy of
as
based upon radiological methods. All are agreed that the facts must be pieced carefully together, and may under certain circumstances justify a grave suspicion of aortitis. Even then the specific nature of the lesion does not follow, and arterio-sclerotic forms of aortitis may be mistaken for those due to syphilis.
diagnosis
* A paper read before the March 16th, 1933. 5731
5731
Liverpool Medical Institution,
In making a differential diagnosis, a positive Wassermann reaction is of moment and may be called forth by a provocative dose of organic arsenic, but is by no means conclusive of the syphilitic nature of the disease. Search should be made for other signs of syphilis, for example, of the nervous system or viscera, and the past history of the patient must be considered. Any suspicion of aneurysmal dilatation is much in favour of syphilis, whilst aortic leakage in the absence of a rheumatic history and particularly in persons over 35 is nearly always syphilitic. Aneurysm, the direct sequel of aortitis, needs little discussion in this paper, for its diagnosis is sufficiently familiar and its syphilitic origin universally admitted. AORTIC REGURGITATION
Another
of syphilitic aortitis deserves of the occasional difficulty in separating syphilitic cases from those due to rheumatism and other causes. Aortic leakage is sometimes found in old age associated with arterio-sclerotic dilatation of the aorta, but cases of this type are rare and can be dismissed here. Another cause of aortic incompetence sometimes overlooked in differential diagnosis is infective endocarditis, especially in its subacute form. If systematic search is made in all valvular lesions for pyrexia, enlargement of the spleen, petechiæ, clubbing of the fingers, hsematuria, and other signs of systemic infection this possibility will not escape the observer. Rupture of the aortic cusps is an unusual cause of incompetence with a characteristic history of severe trauma. When these rare causes have been excluded the diagnosis as a rule rests between aortic regurgitation of rheumatic and of syphilitic origin. In distinguishing these, age is of first importance--the rheumatic type generally occurring in children and young adults, the syphilitic in middle age. Rheumatic cases may not, of course, be recognised until mid-life, especially when the damage to the valves has been limited and non-progressive. The history, though at times conclusive, is frequently of little value, for it is well known that mild forms of rheumatism may escape notice, while a history of syphilis is often concealed. The coincidence of mitral valve defects is generally in favour of a rheumatic origin for the aortic disease, but the presence of an Austin Flint presystolic murmur at the mitral area may lead to difficulty. Clinical or radiological evidence of enlargement of the left auricle suggests mitral disease, as may right ventricular preponderance and increase in the amplitude and duration of the P-waves in the
sequel
attention in view
electrocardiogram. MYOCARDIAL LESIONS
.
The frequency with which syphilis attacks the myocardium is much in dispute. On clinical grounds the diagnosis of syphilitic myocarditis has always proved difficult, and certain pathologists claim that it occurs with much greater frequency than would 5
Warthin appear from observations in the wards. in particular emphasised its great frequency. He found what he considered to be evidence of syphilitic myocarditis, sometimes slight, sometimes great, in every male patient with latent syphilis. In females the incidence was much less. Warthin described microscopic features which he considered pathognomonic of syphilitic myocarditis, and in many cases was able to demonstrate the presence of spirochætes. His views, therefore, cannot be dismissed lightly. A
2
Unfortunately, however, other investigators have been unable to confirm his observations. Clawson and Bell,6 for example, after examining 126 cases of syphilitic aortitis, found that the myocardial changes were such that in most cases they could be accounted for by a mild non-specific coronary disease. Again, Martlandstates that specific lesions of the myocardium and of the coronary arteries beyond the aortic wall are infrequent and usually so slight as to be unimportant. In spite of these conflicting statements, the majority of workers would agree that myocardial involvement is by no means rare in cardiovascular syphilis. Such involvement might be brought about by direct invasion of the myocardium with the Spirochmta pallida or its toxins, at a stage of the disease which will be discussed subsequently, or it might be due to specific changes in the coronary arteries due to extension from a syphilitic aorta. Coronary disease of this kind would inevitably impair the blood-supply to the myocardium. In establishing a diagnosis of syphilitic myocarditis no single physical sign must be given undue prominence. This platitude deserves emphasis in all types of myocardial lesion. Some authorities consider that idiopathic hypertrophy of the heart (Carter and Baker 8; Martland 7) is suggestive of a syphilitic origin, and most would agree that when the hypertrophy is found without valvular disease, arterial hypertension, or arterio-sclerosis, syphilis should be considered seriously as the cause. Especially is this the case in middle-aged persons in whom a rheumatic origin is unlikely. In a series of 232 cases of syphilis examined by Chamberlain and Follows, 11 were found by palpation and percussion to have cardiac hypertrophy with no other abnormal signs, and several of these were young persons. The symptomatology of syphilitic myocarditis is not pathognomonic; breathlessness, palpitations, precordial pain, and other features being common to all types of myocardial lesions. Some have stressed the occurrence of breathlessness and pain at night, but I have been unable to satisfy myself that this is a genuine point of difference between syphilitic and other heart lesions. On the other hand, certain negative features may prove of value in distinguishing syphilitic from other forms of myocardial lesion. Auricular fibrillation or other irregularities rarely occur as a result of syphilis. Coronary infarction is more frequently associated with arterio-sclerotic than with syphilitic changes in the coronary arteries, and its occurrence is against a diagnosis of syphilis. The Wassermann test is, of course, most necessary and very valuable if allowance is made for the high incidence of a positive reaction amongst a population who may develop heart disease of non-specific origin. Moreover, true cases of cardiovascular syphilis undoubtedly occur with a negative Wassermann reaction. In the latter group, a provocative dose of neokharsivan may produce a conclusive response. Finally, the electrocardiograph may assist in the diagnosis of myocarditis, but does not (as stated by some workers) give any clue to the syphilitic nature of the disease. The electrocardiogram may reveal unsuspected myocardial disease by the presence of abnormal T-waves, bundle-branch block, and delayed conductivity in the bundle of His. In the 232 cases examined by Chamberlain and Follows, of whom 221 were electrocardiographed, gross electrocardiographic defects were found in six cases, and minor but suspicious defects in a further seven. These results included cases of T-wave negativity and partial bundle-branch block, and with a few exceptions there
no clinical evidence of cardiovascular disease. Clinical defects without electrocardiographic abnormality were present in the 11 cases .of cardiac hypertrophy previously mentioned, and in three cases of aortic regurgitation, two of whom showed a normal electrocardiogram. The results of the investigation emphasise the importance of combined clinical and
was
electrocardiographic this type.
examination in
investigations
of
STAGE OF INVASION IN CARDIAC SYPHILIS
The view of Warthin, that the spirochæte invades the myocardium and aorta during the stage of bacteræmia—i.e., in the secondary stage of syphiliswould lead one to expect changes in the heart and aorta in this phase of the disease, for the spiroch2ate is capable of producing an intense reaction in the tissues it invades. Yet the number of recorded cases of cardiovascular disease in the secondary stage is small, and many authorities cast doubt upon them. The general consensus of opinion supports the view that after the secondary stage the spirochaete lies latent in the body for 15-25 years before attacking the cardiovascular and other tissues. In this dormant period little is known of its activities, but there is much to suggest that its resting place is in the mediastinal glands, from which at a favourable time it may gain ready access to the heart and aorta. This "
lymphogenous " theory
was
convincingly put
forward by Carey Coombs9 and was based on the observations of Klotz/" Martland,7 and others. Whilst common experience dictates that heart disease does not occur until 15-25 years after the primary syphilitic infection, there are undoubtedly many cases which arise within a shorter interval. The recognition of these is of great importance, for in younger persons their course may be more rapid but more amenable to treatment. For their detection all methods of examination-clinical, electrocardiographic, and radiological-may be necessary. COURSE AND TREATMENT OF CARDIAC SYPHILIS
The outlook in clinically recognisable cardiovascular syphilis is unfavourable, most cases following a progressively downward course. Willius 11 found that the duration of cases of syphilitic aortitis and aortic regurgitation averaged 23 years from the occurrence of primary syphilis, aneurysm averaging 26 years. The greater part of this period would be occupied by the so-called " latent " period, in which no symptoms are manifest and in which the disease is usually undetectable. In some cases the electrocardiograph or X ray might demonstrate suspicious changes while the patient was still symptomless, and in this type of case a repetition of antisyphilitic treatment might stay the advance of the visceral changes. Even when cardiovascular syphilis is clinically
apparent, a course of suitable treatment may modify gloomy prognosis. The work of Moore and Danglade 12 suggests that life may be prolonged from 9 to 69 months in aneurysm, and in aortic regurgita-
the
tion from 32 to 65 months. The manner in which death is brought about by cardiovascular syphilis is variable and presents few characteristic features. In aortic regurgitation death may occur from gradual congestive heart failure or suddenly from defective filling of the coronary vessels. Syphilitic heart disease as a cause of sudden death is emphasised on clinical grounds by Martland7 and on pathological grounds by Warthin.13 The latter states that " it occurred five times more frequently in syphilitic than in non-syphilitic autopsies."
3 The treatment of cardiovascular syphilis has always been a vexed problem. Some have advocated heroic antisyphilitic measures irrespective of the type and grade of the cardiac lesion ; others have held with depressing fatalism that treatment has no effect whatsoever. Even of the time-honoured administration of iodides a German cynic writes : Wenn mann nicht weiss wo, wann, Denn gibt man Iodkalium."
warum
The indiscriminate treatment of all cases of cardiac syphilis, especially with arsenicals, cannot be too strongly condemned. It is well known that an aggravation of local symptoms, called the Herxheimer reaction, may take place after intensive administration of antisyphilitic remedies, especially arsenic preparations, but may be prevented by careful alternation between heavy metals-i.e., mercury or bismuth, and arsenicals. Similarly a therapeutic paradox has been described by Wile 14 relating specially to the cardioIn this there is a remarkable vascular system. improvement in the patient’s general condition after the administration of arsenicals, shortly followed by aggravation of the local cardiac symptoms. The explanation of this phenomenon is uncertain, but it has been suggested that the syphilitic products may be too rapidly replaced by scar tissue, or that their disintegration produces chemical substances with a deleterious influence on the local lesion. If accidents in therapy are to be eliminated cases must be selected with care, and treatment must be cautious. With these reservations there is every reason to believe that treatment may be of value not only in relief of symptoms but in the prolongation of life. In choosing suitable cases, one of the guiding principles should be the state of the cardiac reserve. Cases of decompensation with cedema, enlarged liver, or other congestive signs require restoration of compensation by the usual remedies, such as digitalis and rest, before any antispecific treatment can be carried out with safety. When compensation is good or has been restored by treatment, the patient may commence antisyphilitic measures. A good rule is to begin with iodides and mercury or bismuth, and note the response before using arsenic. Treatment with iodides and the heavy metals may be continued for 6-12 weeks before any arsenic is given. Although it is difficult, without a large number of cases, to compare the effects of one drug with another, I have gained the general impression that bismuth gives better results than mercury in cardiovascular syphilis, especially when pain is a prominent symptom. It may be given in initial doses of 0-1 g., usually contained in 0-5 c.cm. of one of the suspended preparations, such as Bismostab, and the dose increased to 0-2 g. after three or four weeks. Six to eight weekly injections should be given. If the patient shows sufficient response to these lines of treatment, small doses of arsenic may next be given. Various preparations are recommended. Kharsulphan and Neokharsivan are reliable preparations, but should be given in small initial doses, say of 0-1 g., and gradually increased over a course of ten to twelve weeks. American workers recommend Neoarsphenamine or Bismarsen in similar doses. In aortitis the same principles may be adoptedviz., preliminary iodides and a heavy metal, followed by cautious arsenic administration, but here the preparation of most value appears to be Tryparsamide, given in doses of 0-5 g. increasing to 1-0 g. Adverse symptoms such as the Herxheimer reaction and Wile’s therapeutic paradox are indications for the
discontinuance of arsenicals and reliance must then be placed on careful use of bismuth and iodides. It is still uncertain whether specific measures prevent the progress of early syphilitic lesions such as aortitis and myocarditis, but as there is some evidence in favour of this it seems only right that the patient should have the benefit of full treatment, repeated at necessary intervals. When gross structural changes have occurred, as in aneurysm or grave aortic incompetence, the most that can be hoped for is arrest in the progress of the disease and relief of symptoms, and these cases above all require careful handling, usually responding better to iodides and bismuth than to arsenicals. If there is a probability of gummatous collections in the heart, involving, for example, the bundle of His or its branches, fuller doses of iodides-grs. 60-120 daily-may be worth a trial. It is well known that large doses of iodides are also of value in relieving the pain of syphilitic aortitis and aneurysm. Arsenicals should be prohibited in advanced cases of aortic disease and aneurysm, and in patients showing evidence of serious coronary disease generally detected by electrocardiographic means. Bismuth, mercury, and iodides are rarely dangerous, but even they require gentle administration, and should be discontinued if the results are obviously adverse. In conclusion, I should like to express my thanks to Dr. A. A. Fitch and Dr. A. 0. F. Ross, who have .given me free access to their clinics and much
valuable
help. REFERENCES
1. Kurtz, C. M., and Eyster, J. A. E. : Amer. Heart Jour., 1930, vi., 67. 2. Ingraham, R., and Maynard, E. P. : Ibid., p. 82. 3. Bach, F., and Worster-Drought, C.: THE LANCET, 1930, ii., 1113. 4. Steel, David: Amer. Heart Jour., 1930, vi., 59. 5. Warthin, A. S.: Brit, Med. Jour., 1929, ii., 236. 6. Clawson, B. J., and Bell, E. T. : Arch. Path. and Lab. Med., 1927, iv., 922. 7. Martland, H. S.: Amer. Heart Jour., 1930, vi., 1. 8. Carter, E. P., and Baker, B. M.: Bull. Johns Hopkins Hosp., 1931, xlviii., 315. 9. Coombs, Carey F. : Quart. Jour. Med., 1932, xxxv., 179. 10. Klotz, O. : Amer. Jour. Med. Sci., 1918, civ., 92. 11. Willius, F. A.: Amer. Heart Jour., 1930-31, vi., 113. 12. Moore, J. E., and Danglade, J. H. : Ibid., p. 148. 13. Warthin, A. S. : Ibid., p. 163. 14. Wile, W. J. : Ibid., p. 157.
DEVELOPMENTS
AT
HARROGATE.—On
Saturday,
June 17th, Lord Horder opened the new sun colonnade which is the latest amenity at Harrogate. Speaking of British health resorts in general, he said that" we are only now beginning to appreciate the possibilities offered by the medicinal waters of our own country," but " in the matter of spa treatment, at any rate, the facilities at our disposal are as good in Great Britain as they are abroad." Given the energetic and intelligent cooperation of the doctors, the municipal authorities, and the town, he said, there was no reason whatever why British spas should not be as successful and as popular as their continental rivals. But success here, as in all other matters, presupposed courage, foresight, and intelligence. The people of Harrogate had been wise, he thought, in their latest attempt to bring the human gifts of design and adaptation to bear upon natural beauty, and the new promenade was only the first part of a large and necessary scheme to improve the facilities offered. The colonnade or sun walk is 600 feet long, is roofed with vita glass, and broadens into bays at two points, terminating in a cafe and concert hall. The next part of the scheme is the erection of a new pump-room, whose eventual cost will be jE60,000.