Published online by Cambridge University Press: 20 January 2005
Turner's syndrome is a genetic abnormality in females in which the cell nucleuses lack one of the two X chromosomes, resulting in a 45 X 0 Karyotype. The typical features include failure of sexual maturation associated with gonadal dysgenesis, webbed neck, short stature, low-set ears, wide mouth and downward slanting palpebral fissures. Cardiac malformations are present in from one-tenth to one-fifth of the cases, the commonest of which are coarctation of the aorta and aortic valvar stenosis. Some of the cardiac anomalies may be surgically correctable, but in many cases there is eventual cardiac decompensation, with progressive failure leading to death. Sudden and unexpected fatal collapse is unusual and we present, to the best of our knowledge, the first published description of sudden death linked to thromboembolism in a case of Turner's syndrome.
Miss G S was known to have Turner's syndrome, with aortic stenosis and coarctation of the aorta, with gradual deterioration of both left and right-sided ventricular function. At the age of 15 years she was diagnosed as having intestinal angiodysplasia. At 36 years, she underwent percutaneous balloon dilation of the aortic coarctation and insertion of a stent, with considerable clinical improvement. Three years later she was admitted to her local hospital with pneumonia, and was noted to have signs of congestive heart failure, with retention of fluids. An echocardiogram at that time showed impairment of systolic function. Her condition improved on diuretic therapy, and she remained free from orthopnoea, chest pains or syncope, being in the second of the six grades established by the New York Heart association for assessment of function. She was reassessed six weeks later at the tertiary centre, where she was found to be pink and well. Her blood pressure was 130/90 mmHg, with systolic blood pressure in the left leg 135 mmHg, and no delay of the femoral compared to the radial pulses. The jugular venous pressure was elevated.
On chest auscultation, there was a fourth heart sound, a normal first sound murmur, an increased pulmonary component of the second sound, and a grade 3/6 systolic murmur at the right upper sternal border. The lung fields were clear. An electrocardiogram showed sinus rhythm at 120 beats a minute, with a normal PR interval and a left bundle branch block pattern, with a QRS duration of 120 ms. An echocardiogram showed a bifoliate aortic valve, with narrowing of the left ventricular outflow tract. The aortic root was small, being measured at 2.5 cm, and there was moderate to severe stenosis of the aortic valve, with a velocity across it of 3.5 m a second. The left ventricle was of normal size, without significant hypertrophy, but there was moderate systolic impairment, with an ejection fraction of 41%. The right ventricle was mildly dilated, with good systolic function. Both atriums were dilated, and there was mild tricuspid regurgitation. The estimated systolic pressure in the pulmonary arteries was 70 to 80 mmHg.
An early replacement of the aortic valve was planned, but one month later, before this could be done, she complained of chest pain one evening, and was found a few hours later unconscious and gasping. On emergency admission to hospital, an electrocardiogram showed a broad-complex tachycardia, with the chest X-ray showing cardiomegaly, and she was hypotensive. Emergency echocardiography showed a small left ventricle, with impaired systolic function, an akinetic and distended right ventricle, a dilated right atrium, a large mobile mass in the left atrium, and a stenosed bifoliate aortic valve. She was in severe cardiogenic shock with acidosis and hepatic and renal failure. Unfortunately, she did not respond to resuscitation and medical treatment, and died a few hours later. Death was attributed to obstruction of the mitral valve by a ball-valve thrombus in the left atrium.
The body was that of a moderately built Caucasian female 147 cm tall. She had low-set ears, a webbed neck, widely spaced nipples, and multiple widespread pigmented naevuses, these being typical external features of Turner's syndrome. There was pitting oedema of both feet, but no external evidence of anaemia, jaundice, clubbing, lymphadenopathy or cyanosis.
Internal examination was limited to the chest. There were small bilateral clear pleural effusions of 250 ml on the right side, and 100 ml on the left side. Both lungs were congested and showed chronic passive venous congestion, more pronounced in the lower lobes. The heart, with great vessels attached, including the thoracic portion of the descending aorta, weighed 390 g. There was moderate left ventricular hypertrophy.
The atriums were arranged in usual fashion, and both were moderately dilated. A persistent left superior caval vein drained into the right atrium through the coronary sinus, which was dilated to 2 cm in diameter. A pulmonary vein, approximately 0.7 cm in diameter, from the upper lobe of the right lung, opened anomalously into the right azygos vein just before its junction with the dilated right superior caval vein (Fig. 1).
Figure 1. The dilated right superior caval vein (RSCV) receives the azygos vein (AzV) and an anomalous pulmonary vein (APV), and opens into the right atrium (RA). The aorta (Ao) has been displaced.
Within the left atrial cavity, there was a large, firm, ovoid thrombus, 4 cm long, and measuring 3 cm in diameter at one end, and 1.5 cm in diameter at the other end. The thrombus had a reticulated surface, with well-marked lines of Zahn. The cut surface showed a laminated structure. It was loosely attached to the atrial septum near the region of the oval fossa, and impinged upon the opening of the mitral valve (Figs 2 and 3).
Figure 2. The left atrium (LA) is opened from behind to show the contained thrombus (arrowed). The dilated coronary sinus has been cut across (CS). LV: left ventricle.
Figure 3. The left atrial thrombus showing the reticulated surface.
The atrioventricular connections were concordant, albeit that both atrioventricular valves were abnormal. The septal leaflet of the tricuspid valve had a thick rolled margin, and the tendinous cords were shortened. It appeared, nonetheless, to be fully patent and probably competent. The mitral valve was dysplastic and deformed, with short tendinous cords enmeshing fibrinous fragments. This valve appeared to be both stenosed and incompetent, with an orifice of only 1 cm in diameter (Fig. 4).
Figure 4. The interior of the left side of the heart. The restricted orifice of the mitral valve is indicated by the black arrowheads. The dilated coronary sinus has been cut across (CS). LA: left atrium; LV: left ventricle.
The ventriculo-arterial connections were also concordant. The aortic valve was grossly abnormal, presenting as a rigid dome with a central orifice only 0.7 cm in diameter. A solitary rudimentary and irregular zone of apposition produced a unicommissural and unifoliate structure (Fig. 5).
Figure 5. The stenosed aortic valve viewed from above. The single commissure is indicated by the large arrow. The two basal nodules, indicated by the small arrowheads, may represent rudimentary commissures. The orifices of the right and left coronary arteries are also indicated (RCA, LCA).
The ascending aorta was approximately 2.8 cm in diameter at its origin. The arch was to the left, and the branching was normal, except that there was an unduly long gap of 2 cm between the origins of the left common carotid artery and the small, narrow, left subclavian artery. A pre-existing coarctation shelf had been dilated up to 2 cm in diameter, and contained a stent, 3 cm long, which extended from 0.5 cm above the origin of the left subclavian artery. The orifice of the artery within the stent was severely restricted, measuring only 1 to 2 mm in diameter. The distal portion of the thoracic aorta was 1.0 cm in diameter. There was no evidence of major arterial anastomotic channels, and the orifices of the intercostal arteries were not enlarged (Fig. 6).
Figure 6. The great arterial trunks and their branches. Ao: aorta; RCC, LCC: right and left common carotid arteries; RSA, LSA: right and left subclavian arteries; PT: pulmonary trunk; LPA: left pulmonary artery; AL: arterial ligament. The extent of the stented segment of the coarcted aorta is indicated by the double-headed arrow.
The orifices of the coronary arteries were normal, and the main arteries and their branches pursued normal courses and appeared to be fully patent and free from atheroma. On opening the anterior descending branch of the left artery, a small white spherical embolus, barely 0.25 cm in diameter, was found within the lumen, apparently impacted into the mouth of a perforating branch, 3.0 cm from the aortic orifice (Figs 7 and 8). There was no macroscopic evidence of myocardial infarction. Histological examination demonstrated a marked similarity between the thrombus in the left atrium and that blocking the coronary artery, with no evidence of infection. Sections of the anterior wall of the left ventricle showed early ischaemic changes of the myocardial fibres, with contraction band necrosis (Fig. 9). There were also smaller emboluses within the intramural vessels (Fig. 10).
Figure 7. The anterior descending branch of the left-coronary artery (ADBOLCA) is opened to show the thrombo-embolus within (arrowed).
Figure 8. Histological section of the coronary artery with the embolus still in place, occluding a perforating branch.
Figure 9. High power view of myocardial fibres of the left ventricle showing early ischaemic necrosis.
Figuer 10 An organising thrombo-embolus occluding a coronary arteriole.
Multiple congenital cardiac abnormalities are present in about one tenth to one fifth of patients with Turner's syndrome. In our patient, the two commonest associated cardiac malformations had been accurately diagnosed before they had become unmanageable. The aortic coarctation had been successfully treated by percutaneous transluminal dilation and stenting, whereas the aortic stenosis was due to be dealt with surgically. Had the terminal illness not intervened, it is highly probable that this too would have been successfully relieved. The real “villain of the piece” would seem to have been the congenital stenosis of the mitral valve, which was not of sufficient severity to express itself clinically or echocardiographically in the presence of the other lesions. In the known absence of atrial fibrillation, nonetheless, it is probable that this was partly responsible for the development of the large thrombus within the left atrium as, together with the aortic stenosis, it reduced the flow of blood through the left heart. Her previous pneumonia may well have contributed to the thrombosis. Distal thrombo-embolic phenomenons are a common complication of atrial thrombosis, and their occurrence in this case, with lethal consequences, was confirmed histologically. The cardiac defects in Turner's syndrome are linked particularly to limitations in flow of blood through the left heart. Hypoplasia of the left heart, as well as mitral valvar stenosis, have been described, but the mitral valvar disease in our patient was not considered to be clinically significant. At the time of her final admission to hospital, the patient was in no condition to give a clinical history or describe her symptoms, but there was a veritable plethora of clinical signs, from the non-specific indications of cardiogenic shock with hepatorenal failure, to the specific demonstrations of the aortic stenosis, tricuspid regurgitation, and the massive left atrial thrombus, with apparent ball valve occlusion of the mitral valve. Indeed, these latter lesions could very reasonably be held to be responsible for her condition. Unfortunately the electrocardiogram did not reveal the myocardial ischaemia. The patient was on a single lead monitor trace, no multilead permanent recording was kept, and retrospective review was therefore not possible. Any electrocardiograhpic changes of ischaemia may have been apparent only in selected leads.
It should be stressed that early detection of the myocardial ischaemia would probably not have affected the fatal outcome. Anti coagulation with warfarin was given consideration when she was referred for early surgery to the aortic valve, but was not initiated in view of her history of intestinal angiodysplasia. It is questionable whether thrombolytic therapy would have had any significant effect on the impacted microemboluses composed of fibrin and platelets.
Our case serves to illustrate the cardiovascular malformations which may be associated with Turner's syndrome, albeit with an unexpected fatal outcome. It also demonstrates that the possibility of myocardial ischaemia should always be considered in cases of acute cardiogenic collapse, especially if this is preceded by chest pain, irrespective of age and the presence of congenital malformations. Detailed examination of the coronary arteries is warranted in any autopsy, with or without complex congenital cardiac disease.
The dilated right superior caval vein (RSCV) receives the azygos vein (AzV) and an anomalous pulmonary vein (APV), and opens into the right atrium (RA). The aorta (Ao) has been displaced.
The left atrium (LA) is opened from behind to show the contained thrombus (arrowed). The dilated coronary sinus has been cut across (CS). LV: left ventricle.
The left atrial thrombus showing the reticulated surface.
The interior of the left side of the heart. The restricted orifice of the mitral valve is indicated by the black arrowheads. The dilated coronary sinus has been cut across (CS). LA: left atrium; LV: left ventricle.
The stenosed aortic valve viewed from above. The single commissure is indicated by the large arrow. The two basal nodules, indicated by the small arrowheads, may represent rudimentary commissures. The orifices of the right and left coronary arteries are also indicated (RCA, LCA).
The great arterial trunks and their branches. Ao: aorta; RCC, LCC: right and left common carotid arteries; RSA, LSA: right and left subclavian arteries; PT: pulmonary trunk; LPA: left pulmonary artery; AL: arterial ligament. The extent of the stented segment of the coarcted aorta is indicated by the double-headed arrow.
The anterior descending branch of the left-coronary artery (ADBOLCA) is opened to show the thrombo-embolus within (arrowed).
Histological section of the coronary artery with the embolus still in place, occluding a perforating branch.
High power view of myocardial fibres of the left ventricle showing early ischaemic necrosis.
An organising thrombo-embolus occluding a coronary arteriole.