| disease | Syphilitic Cardiovascular Disease |
| alias | Syphilitic Cardiovascutar Disease |
Syphilitic cardiovascular disease is a condition caused by the invasion of the human body by the syphilis spirochete, leading to cardiovascular diseases, including syphilitic aortitis, syphilitic aortic valve insufficiency, syphilitic aortic aneurysm, coronary ostial stenosis, and myocardial gumma. The vast majority of syphilis cases are acquired, while congenital syphilis is rare. Although cardiovascular syphilis is currently uncommon, it still exists.
bubble_chart Pathological Changes
Syphilis spirochetes are mostly transmitted through sexual contact. Approximately 30% of untreated patients eventually develop advanced stage syphilis affecting the heart, blood vessels, nerves, and other organs, while 10-12% of syphilis patients may develop cardiovascular syphilis lesions. The latent period from initial infection with syphilis spirochetes to the onset of cardiovascular disease ranges from several years to decades, typically 5-25 years. The disease is more common in men than in women, with a ratio of about 4:1 to 5:1. About 10-25% of cardiovascular syphilis cases coexist with neurosyphilis. If the patient is also infected with human immunodeficiency virus (HIV), stage II syphilis can rapidly progress to neurosyphilis, altering the original symptoms of syphilis. Although treatment can alleviate the condition, it is prone to recurrence.
Syphilis spirochetes invade the middle layer of the aorta. In the early stages of infection, after entering the bloodstream, some spirochetes are drained through the hilar lymphatics to the nutrient vessels of the aortic wall, but rarely invade the myocardium or endocardium. In late-stage [third stage] syphilis, the aortic wall often becomes inflamed and scarred. Syphilis can invade any part of the aorta, but the ascending aorta is most commonly affected due to its rich lymphatic tissue, which facilitates the entry of syphilis spirochetes. The middle layer of the aorta, consisting of muscle and elastic tissue, is invaded and destroyed by syphilis spirochetes, leading to inflammation and obstructive endarteritis, accompanied by perivascular infiltration of plasma cells and lymphocytes. These cells can sometimes cause tissue hyperplasia, and the normal tissue of the aortic middle layer is replaced by fibrous tissue. Giant cells and small syphilitic gummas can also be found in the affected aorta.
Due to inflammation, the aortic wall gradually becomes lax and may calcify, potentially leading to the formation of an aortic aneurysm. The endothelium develops folds covered with large patches of shiny, pearl-like material. The "tree bark" appearance of the aorta is characteristic of syphilitic aortitis, but it cannot be used as definitive evidence for diagnosis.Syphilis infection can spread from the ascending aorta to the aortic root, causing dilation of the aortic ring and separation of the aortic valve commissures, resulting in aortic valve insufficiency. The destruction of the aortic valve support structures and the curling and shortening of the aortic valve leaflets lead to severe aortic valve regurgitation.
bubble_chart Clinical Manifestations
According to the extent and impact of the lesions, there are five clinical types, and a single patient may exhibit one or more types.
(1) Simple syphilitic aortitis: Syphilitic aortitis can occur in the early stages of syphilis but is more commonly seen in advanced syphilis. It mostly occurs in the ascending aorta but can also affect the distal descending aorta. Clinically, it is usually asymptomatic and difficult to diagnose, with clinical manifestations often appearing 10 to 13 years after the onset.
1. Symptoms: Among untreated syphilis patients, over 80% develop syphilitic aortitis, most of whom are asymptomatic. Some patients may experience retrosternal discomfort or dull pain, and 10% may develop complications such as aortic aneurysm, aortic valve insufficiency, or coronary ostial stenosis.
2. Signs: Due to aortic dilation, the dullness boundary above the heart widens during percussion. The second heart sound in the aortic valve area is enhanced, and a grade I systolic murmur may be heard, though the nature of this murmur is nonspecific.
1. Symptoms: The severity varies greatly. Mild cases may be asymptomatic, while severe cases, due to significant aortic valve regurgitation and possible concurrent coronary ostial stenosis, may experience reduced coronary blood flow leading to angina. The severity of angina may not correlate with the degree of aortic valve regurgitation. Persistent aortic valve regurgitation increases the load on the left ventricle, gradually leading to left heart failure. Once heart failure occurs, the disease progresses rapidly within 1 to 3 years, leading to pulmonary edema and right heart failure, with half of the patients dying.
2. Sign: Percussion reveals an enlargement of the cardiac dullness border to the lower left, due to the widening of the ascending aorta and aortic arch. The dullness border at the second intercostal space on the right sternal border may also widen. The apical impulse is often enhanced. In the early stages of inflammation involving the aortic valve, auscultation often reveals an accentuated second heart sound in the aortic valve area. In the late stage [third stage] of the disease, as the aortic valve itself undergoes fibrous contraction and loses mobility, the second heart sound in the aortic valve area gradually diminishes and may eventually disappear. When aortic valve regurgitation occurs, a to-and-fro systolic and diastolic blowing murmur can be heard at the second intercostal space on the right sternal border or the third and fourth intercostal spaces on the left sternal border, with the clearest sound at the second intercostal space on the right sternal border. Due to the dilation of the aortic root, the diastolic blowing murmur is loudest at the second intercostal space on the right sternal border and radiates to the apical area. In terms of the location of the murmur, syphilitic aortic valve insufficiency differs from rheumatic aortic valve insufficiency, as the latter is often accompanied by mitral valve disease, right ventricular enlargement, and cardiac displacement, causing the diastolic blowing murmur to be clearest at the third intercostal space on the left sternal border. In rare cases, the right anterior leaflet of the aortic valve may prolapse into the left ventricle, producing a musical grade 3-4 diastolic murmur, which may be accompanied by a thrill. The murmur is loud and seagull-like, and if not carefully noted, it may be mistaken for a systolic murmur. Aortic ring calcification, stiffness at the base of the aortic valve leaflets, and proximal aortic dilation can result in a loud systolic ejection murmur, which intensifies in early systole but is of shorter duration. This murmur is also loudest at the second intercostal space on the right sternal border and radiates to the neck. Sometimes, a thrill may be palpable at the common carotid artery or the suprasternal notch but is rarely felt in the aortic valve area. These manifestations differ from rheumatic aortic stenosis, where the murmur is higher-pitched and sharper, intensifying in the intermediate [second] or advanced stages of systole. In syphilitic aortic regurgitation, a loud snapping systolic ejection sound can be heard in the aortic valve area, originating from the sudden expansion caused by a large volume of blood entering the dilated aorta in early systole. In severe aortic regurgitation, in addition to the murmur transmitted from the aortic valve area, a rumbling diastolic murmur may be heard at the apical area, with limited radiation. This murmur arises from the functional mitral stenosis caused by the impact of regurgitant blood on the anterior mitral leaflet, known as the Austin-Flint murmur. This murmur lacks presystolic accentuation and is not accompanied by an accentuated first heart sound or mitral opening snap, distinguishing it from rheumatic mitral stenosis. Atrial fibrillation is common in syphilitic cardiovascular disease, possibly related to coronary ostial obstruction caused by sexually transmitted disease. In severe syphilitic aortic valve insufficiency, a large volume of diastolic blood regurgitates into the ventricle, lowering diastolic blood pressure, sometimes almost to zero, with widened pulse pressure. This leads to various peripheral vascular signs, including water-hammer pulse (Corrigan's sign), pistol-shot sound (Traube's sign), capillary pulsation (Quincke's sign), and less commonly, Müller's sign (tonsils reddening with each heartbeat), de Müsset's sign (head nodding with each heartbeat), Landolfe's sign (pupil constriction during systole and dilation during diastole), and Shelley's sign (systolic pulsation in the neck). Hyperdynamic cardiovascular pulsations may sometimes cause periodic rocking of the bed.
(4) Syphilitic aortic aneurysm is the least common clinical manifestation of syphilitic aortitis and is a direct consequence of syphilis invading the aorta. It most commonly occurs in the thoracic aorta, with 50% occurring in the ascending aortic arch, presenting as saccular or fusiform but never dissecting. Aneurysms in different locations compress surrounding organs and tissues, producing corresponding symptoms and signs.
1. Ascending aortic aneurysm: A systolic vascular murmur can be heard over the body surface where the aortic aneurysm is located. If the aortic aneurysm does not compress adjacent tissues, there are no symptoms. An ascending aortic aneurysm may cause a local bulge with noticeable pulsation in the right anterior chest at the first and second intercostal spaces, and pulsation may also be visible at the right sternoclavicular joint or suprasternal notch. Compression and erosion of the sternum by the aneurysm can cause pain; compression of the superior vena cava or innominate vein can lead to facial and upper limb edema, distension of neck, upper limb, and chest wall veins, exophthalmos, conjunctival edema, and dyspnea (superior vena cava syndrome); compression of the trachea or bronchi can cause shortness of breath, dyspnea, metallic cough, atelectasis, and recurrent lung infections; in rare cases, compression of the pulmonary artery can produce signs of pulmonary artery stenosis and may lead to right heart failure; nerve compression or bone erosion can also cause pain.
2. Aortic arch aneurysm: Aortic arch aneurysms often compress surrounding organs and cause symptoms early. Erosion of the trachea or bronchi can lead to hemoptysis; compression of the recurrent laryngeal nerve can cause hoarseness or a metallic cough; compression of the intercostal nerves can result in persistent chest pain; compression of the left bronchus can cause bronchial stenosis or atelectasis, with patients experiencing panting, and symptoms alleviated when lying on the right side or sitting and leaning forward, and worsened otherwise; compression of the esophagus can lead to dysphagia; compression of the phrenic nerve can cause hiccups or diaphragmatic paralysis; compression of the left stellate ganglion can result in Horner's syndrome (cervical sympathetic paralysis syndrome) with ptosis, miosis, and reduced sweating on the left side of the face; compression of the superior vena cava can produce superior vena cava syndrome, manifesting as distension of neck and upper chest veins, downward blood flow, congestion and edema of the head, neck, upper limbs, and upper trunk, dark red skin, conjunctival redness, rapid breathing, and hoarse cough.
3. Descending thoracic aortic aneurysm: Descending thoracic aortic aneurysms can be very large without causing symptoms and are often discovered during routine chest X-rays or X-rays for other diagnostic purposes. A few patients may experience pulsation below the left scapula. Compression of the main bronchi by the aneurysm can cause cough and dyspnea, compression of the pulmonary artery can lead to pulmonary artery stenosis, compression of the lungs can cause secondary lung infections, and compression of the pulmonary veins or azygos vein can result in pleural effusion.
Syphilitic abdominal aortic aneurysms often occur at the level of the 12th thoracic vertebra to the 2nd lumbar vertebra. Sometimes a pulsatile mass can be palpated in the abdomen, and if the aneurysm compresses the renal artery, it can cause hypertension.
Descending thoracic aortic and abdominal aortic aneurysms can occasionally compress spinal nerve roots, causing severe pain, vertebral atrophy, and spinal cord compression.
Stirred pulse tumors, regardless of whether they are symptomatic, may rupture at their location. Stirred pulse tumors in the thoracic cavity can rupture into the pericardium, pleural cavity, esophagus, or trachea and bronchi, causing massive hematemesis or hemoptysis; abdominal stirred pulse tumors often rupture into the retroperitoneal space or abdominal cavity, and can also rupture into the intestines. In very rare cases, they may rupture into the right heart chamber or pulmonary stirred pulse, producing a continuous murmur. If the murmur is mainly located at the left second intercostal space, it may present similarly to a patent stirred pulse duct or a defect in the septum between the main and pulmonary stirred pulse. In extremely rare cases, a ruptured main stirred pulse tumor may close on its own and stop bleeding, while the rest often die within a few hours to a few days.
The early stages of a sinus of Valsalva aneurysm occurring at the root of the main Valsalva pulse are very difficult to detect. If the Valsalva pulse tumor occurs in the left and right main Valsalva sinuses and affects the coronary Valsalva opening, it can cause heart colicky pain; if it occurs in the posterior main Valsalva sinus, the Valsalva pulse tumor is asymptomatic or shows no signs unless it ruptures. A rupture of the main Valsalva sinus aneurysm into the pulmonary Valsalva or right heart chamber can lead to severe right heart failure, causing a continuous murmur, similar to a patent Valsalva duct or a defect between the main and pulmonary Valsalva; occasionally, the Valsalva pulse tumor ruptures into the left atrium, producing a continuous murmur in the back and left heart failure.
(5) Myocardial gumma Myocardial gumma involving the heart muscle is extremely rare, although it can occur in any part of the heart muscle, the most common site is the left ventricle, at the base of the ventricular septum. The diagnosis of localized or diffuse myocardial gumma is very difficult and is often made postmortem. Clinically, it manifests as conduction block or myocardial infarction, with localized sexually transmitted disease changes being asymptomatic, but if it invades the valve membrane orifice, causing pseudo-stenosis of the valve membrane, it produces symptoms and signs of valve membrane stenosis. Diffuse myocardial gumma can cause intractable heart failure.
bubble_chart Auxiliary Examination
(1) Serological Tests The range of syphilis serology includes methods with lower specificity and sensitivity to highly specific and sensitive methods, mainly including the following.
1. Wasserman's test and Kahn's test were previously commonly used for serological testing of syphilis. They have now been replaced by more sensitive and specific methods.
2. Non-treponemal serological tests (non-specific reagin antibodies) include the VDRL test (Veneral Disease Research Laboratories, Sexually Transmitted Disease Research Laboratory), RPR (Rapid Plasma Reagin) test, and APT (Automated Reagin) test, commonly used for syphilis screening. The VDRL test has a positivity rate of 70% in initial stage [first stage] syphilis, 99% in secondary stage syphilis, and 70% in advanced stage syphilis (including cardiovascular and neurosyphilis). If co-infected with HIV, the reaction in initial stage [first stage] and secondary stage syphilis tests may be delayed or the positivity rate may decrease.
3. Treponemal tests for syphilis include the Treponema pallidum immobilization test (TPI test), Fluorescent Treponemal Antibody Absorption test (FTA-ABS test), and Microhemagglutination Assay for Treponema pallidum (MHA-TP), all of which are positive. The FTA-ABS test has a positivity rate of 70% in initial stage [first stage] syphilis, 99% in secondary stage syphilis, and 98% in advanced stage syphilis, and can be used as a confirmatory test, as well as a positive test for cardiovascular and neurosyphilis. The MHA-TP test is less sensitive than the VDRL and FTA-ABS tests in initial stage [first stage] syphilis, but similar in sensitivity and specificity to the FTA-ABS test in secondary and advanced stage syphilis. Even after treatment, the FTA-ABS test can remain positive for life.
4. Treponemal IgG antibody detection (Western blot test) has the characteristics of the FTA-ABS test, with 99% sensitivity and 88% specificity, is easy to perform, and is particularly useful for suspected cases of reinfection, congenital syphilis, and syphilis co-infected with HIV.
(2) Imaging Studies
1. Chest X-ray In simple syphilitic aortitis, dilation of the proximal ascending aorta can be seen, with about 20% of patients showing linear calcification of the ascending aorta, while atherosclerotic calcification often appears as lumpy calcification in the descending thoracic aorta. Calcification of the ascending aorta usually appears several years after the onset of syphilitic aortitis. In syphilitic aortitis, the aortic knob and descending thoracic aorta can calcify, but the calcification is most extensive in the ascending aorta near the brachiocephalic artery, whereas in atherosclerosis, the calcification is most prominent in the aortic knob and descending thoracic aorta, which is a distinguishing feature. Syphilitic aortitis lesions start from the aortic root and can extend distally, up to the diaphragm, with widening of the aorta at the lesion site. In the presence of aortic valve insufficiency, the heart enlarges to the left, downward, and posteriorly, taking on a shoe shape, with vigorous and large-amplitude pulsations of the heart and aorta visible on the fluoroscope. In aortic aneurysm, bulging of the aorta is seen at the corresponding site, with expansive pulsations, and aneurysms of the ascending aorta or aortic arch can erode adjacent bones, showing bone destruction, with possible calcification within the aneurysm wall.
2. CT and MRI Examination CT (computed tomography) is used for screening cases suspected by chest X-ray, and it can accurately measure the size of stirred pulse tumors. Its accuracy is comparable to that of ultrasound contrast and stirred pulse contrast, making it a particularly noteworthy new technology. MRI (magnetic resonance imaging) can obtain high-resolution static images and has high diagnostic accuracy for thoracic main stirred pulse lesions. It can display cystic stirred pulse tumors, the true size and characteristics of stirred pulse tumors, and their relationship with surrounding inflammatory reactions. It also shows the extent of stirred pulse tumor involvement and its relationship with the main stirred pulse arch. It has high sensitivity and specificity for detecting heart valve membrane regurgitation.
3. Ultrasound Examination Echocardiography can show widening and calcification of different segments, stirred pulse aneurysm (including main stirred pulse sinus aneurysm), and main stirred pulse valve insufficiency. The amount of regurgitation through the main stirred pulse valve is measured using ultrasound Doppler. It detects the size of the left ventricle, the thickness of the ventricular wall, the end-systolic and end-diastolic pressures and volumes of the left ventricle, and the ejection fraction. It shows abnormal mitral valve activity including anterior leaflet diastolic fluttering. It displays the size, location, and rupture site of the stirred pulse aneurysm.
4. Cardiovascular Angiography Retrograde main stirred pulse angiography shows the location and size of the main stirred pulse aneurysm, the degree of main stirred pulse valve regurgitation, the size of the left ventricle, and the cardiac function status. Selective coronary stirred pulse angiography is used for syphilitic cardiovascular disease patients with heart colicky pain and suspected coronary stirred pulse orifice stenosis. In this disease, coronary stirred pulse stenosis is limited to the orifice, and there is no stenosis in the distal coronary stirred pulse, which is different from coronary stirred pulse atherosclerosis. According to statistics, 20-80% of patients with syphilitic main stirred pulse inflammation have coronary stirred pulse orifice stenosis.
bubble_chart Treatment Measures
After the diagnosis of syphilitic cardiovascular disease is established, anti-syphilitic treatment must be administered to prevent further damage. Penicillin is an effective antibiotic and can be administered using the following two regimens: ① Benzathine penicillin G (bicillin) 2.4 million units intramuscularly once a week for three weeks, totaling 7.2 million units; ② Procaine penicillin G 600,000 units intramuscularly once daily for 21 days. For patients allergic to penicillin, cephaloridine can be used, with 0.5-1g administered intramuscularly daily for 10 days, or erythromycin can be taken orally, 500mg each time, four times a day for 30 days, although it is generally considered less effective than penicillin. During anti-syphilitic treatment, a few patients may experience symptoms such as fever and increased chest pain one day after starting treatment, which are systemic reactions and local edema caused by the massive killing of spirochetes. In rare cases, patients may develop coronary artery ostial swelling and increased stenosis during treatment, leading to sudden death. To prevent such reactions, adrenal corticosteroids can be administered concurrently in the first few days of treatment, such as oral prednisone 10mg every 6 hours. Patients with heart failure must have their heart failure controlled before starting anti-syphilitic treatment. For patients with neurosyphilis or concurrent HIV infection, high-dose penicillin G can be administered intravenously.
Syphilitic aortic aneurysm requires surgical treatment, with indications for surgery being an aortic aneurysm diameter of 7cm, the presence of compressive symptoms, or rapid expansion. The surgery involves resection of the aortic aneurysm and transplantation with a homologous artery or vascular substitute. Patients with significant aortic valve regurgitation may undergo aortic valve replacement. If there are lesions at the coronary artery ostium, a coronary artery ostial membrane stripping procedure must be performed.
The average lifespan of patients with simple aortic valve insufficiency is similar to that of the general population. In the asymptomatic stage of syphilitic aortic valve insufficiency, the duration is approximately 2 to 10 years (average 6 years). After symptoms appear, the average lifespan is 5 to 6 years, with about one-third of patients surviving up to 10 years after symptom onset. Survival time mainly depends on the presence or absence of heart failure or colicky pain. If heart failure occurs, the general survival time is 2 to 3 years, with about 6% of patients surviving more than 10 years. Most patients deteriorate rapidly after cardiac decompensation, and the prognosis is particularly poor for those engaged in heavy physical labor. Patients with coronary artery occlusion generally have a poor prognosis. The prognosis for aortic aneurysm is very poor, with an average lifespan of 6 to 9 months after symptom onset. The 2-year mortality rate is 80%, and the interval from symptom onset to death can be as short as 1 week, primarily due to rupture and obstructive pneumonia.
Syphilis is a product of poor social conditions and the prostitution system. Establishing new morals and customs, and prohibiting illegal sexual intercourse are necessary measures to prevent the spread of syphilis. It is essential to combat drug abuse and actively prevent the spread of AIDS. Early-stage syphilis patients should be treated with penicillin, and serological tests should be followed up, with repeated treatment if necessary.
Patients with syphilitic cardiovascular disease often have a history of promiscuity, typical clinical manifestations of syphilis or advanced-stage syphilis, and positive syphilis serological reactions, making the diagnosis relatively straightforward. However, it should be differentiated from rheumatic valvular disease, atherosclerotic heart disease causing heart murmurs, and some other conditions.
(1) Differentiation of heart valve murmurs
1. Diastolic murmur in the aortic valve area: The regurgitant murmur caused by syphilitic dilation of the aortic root is loudest at the second intercostal space on the right sternal border due to root dilation. In contrast, rheumatic aortic regurgitation, often accompanied by mitral valve disease and right ventricular enlargement, shifts the heart, making the diastolic murmur loudest at the third intercostal space on the left sternal border.
2. Systolic murmur in the aortic valve area: In syphilitic aortic regurgitation, a loud, snapping early systolic ejection sound and systolic murmur can be heard in this area. In contrast, the murmur of rheumatic aortic stenosis is higher-pitched and sharper, intensifying in mid-to-late systole. Although aortic annular calcification with proximal aortic dilation (relative stenosis) can also produce a systolic ejection murmur, it intensifies early in systole and is shorter in duration.
3. Diastolic murmur in the mitral valve area: Severe syphilitic aortic regurgitation causes a functional mitral stenosis due to the impact of blood flow on the mitral valve, producing a diastolic rumbling murmur (Austin-Flint murmur). This murmur lacks presystolic accentuation, is not accompanied by an accentuated first heart sound at the apex, or an opening snap of the mitral valve. In contrast, rheumatic mitral stenosis produces a diastolic rumbling murmur with presystolic accentuation, an accentuated first heart sound at the apex, and an opening snap of the mitral valve.
(2) Differentiation of false-positive syphilis serological reactions
1. VDRL false-positive reactions: During the acute phase of infection (within 6 months), differentiation is needed from atypical pneumonia, malaria, and other bacterial or viral infections. In the chronic phase (beyond 6 months), differentiation is required from autoimmune diseases (e.g., systemic lupus erythematosus), drug use, leprosy, and false-positive reactions in some elderly individuals. These false-positive titers are usually 1:8 or lower, and such patients should be followed up long-term.
2. FTA-ABS false-positive: Cases of systemic lupus erythematosus may show false-positive reactions. This may be due to a beaded fluorescence pattern caused by anti-DNA antibodies, differing from true syphilis-positive results, and requires close follow-up.
(3) Differentiation of angina
Angina is the most common clinical manifestation of syphilitic coronary ostial stenosis. Due to the slow progression of the disease and the support of collateral circulation, myocardial infarction is rare, although coexisting coronary atherosclerosis is often present. The age of onset is earlier than that of coronary heart disease, with episodes often occurring at night and lasting longer.
