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Fatal cardiovascular complications in a patient with Ehlers-Danlos syndrome type IV and dextrocardia
PII: S0967-2109(02)00079-0
Cardiovascular Surgery, Vol. 10, No. 6, pp. 640–643, 2002 2002 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved. 0967-2109/02 $22.00
www.elsevier.com/locate/cardiosur
CASE REPORT Fatal cardiovascular complications in a patient with Ehlers-Danlos syndrome type IV and dextrocardia S. Jazayeri, M. C. Gomez, E. Tatou, M. Saleh, J. P. Parthiot, R. Brenot and M. David Service de Chirurgie Cardio-vasculaire, 2 Bd Mare´chal de Lattre de Tassigny, BP 1542, 21034 Dijon Cedex, France A report is presented of a 31 year female patient with Ehlers-Danlos syndrome type IV who presented a bilateral renal artery dissection and a hematoma of the ascending aorta simultaneously. She had had an uneventful delivery six months before. We also discovered a situs solitus with dextrocardia in this patient. These complications were managed conservatively. Unfortunately the patient died of a pulmonary infection and a multi-organ failure syndrome several days after her admission. 2002 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved. Keywords: Ehlers-Danlos syndrome, renal artery, dissection, dextrocardia, ascending aorta
Introduction Ehlers-Danlos syndrome (EDS) comprises more than 10 genetically, biochemically, and clinically distinct inherited disorders of collagen synthesis. EDS type IV or vascular type, is caused by structural defects in the proα1(III) chain of collagen type III encoded by COL3A1 [1]. This disorder produces defective type III collagen, the major structural component of blood vessels and viscera. As a result of this defect, EDS type IV patients often experience life-threatening cardio-vascular complications [2,3]. We report here a case of EDS type IV, associated with a congenital cardiac dextrocardia (situs solitus) in a young female patient with bilateral renal artery dissection and a hematoma of the ascending aorta, six months after an uneventful delivery.
Case report A 31 year female patient was admitted to our intensive care unit with a diagnosis of a retro-peritoneal Correspondence to: S. Jazayeri. Tel.: +33 380 293354 ; fax: +33 380 293385; e-mail: [email protected]
640
haemorrhage of unknown cause. Two hours before, she had been in profound shock with a slightly distended and painful abdomen. After rapid resuscitation by a mobile emergency unit at home she was admitted to a regional hospital. A CT scan was performed showing large left perirenal and retroperitoneal hematomas (Figure 1). The medical history listed EDS type IV diagnosed at age 14. Six months before she had had a baby after an elective caesarean at 33 weeks’ gestation. The delivery was uneventful, except for a thrombophlebitis of the left lower limb which was treated medically. On admission, she was conscious with a blood pressure of 130/70 mm Hg; heart rate 110 per min. Examination revealed mild abdominal tenderness. Her hematocrite was 30%. The CT scan showed a left peri-renal hematoma, probably due to the rupture or dissection of a left renal artery. The renal arteriography showed dysplasic renal arteries with images of dissection in both sides (Figure 2a and b). There was a severe post-ostial stenosis on the right side. The patient’s hemodynamic condition improved following blood volume replacement, and as her condition remained stable, a decision was made to conCARDIOVASCULAR SURGERY
DECEMBER 2002 VOL 10 NO 6
Fatal cardiovascular complications in a patient with Ehlers-Danlos syndrome type IV and dextrocardia: S. Jazayeri et al.
Figure 1 Computed tomography showing a left perirenal hematoma with a right kidney nonsecretant (arrows).
tinue managing her conservatively. The following day, a transthoracic and transoesophageal cardiac echography showed pericardial effusion (Figure 3) and a very localized hematoma of the ascending aorta with no sign of dissection. A situs solitus with dextrocardia was also diagnosed by pulmonary X ray and cardiac echography (Figure 4a,b and c). It was decided to drain this hemorrhage because of signs of compression on the right ventricle. Unfortunately 24 hours later, she presented spontaneous peri-hepatic and a rectus abdominalis hematomas. A subsequent spontaneous pneumothorax required a thoracic drainage. Finally, a pulmonary infection due to pseudomonas aeroginosa led to her death three days after her admission to hospital.
Discussion Ehlers-Danlos syndrome (EDS) is a heterogenous group of connective tissue disorders. More than ten types of this syndrome are now distinguished by a variety of clinical, biochemical, and genetic characteristics. The true prevalence of EDS remains unknown, it is estimated at about 1/150000 for all types of EDS. Of all the variants, types I–IV are the most common and comprise 95% of type-specific individuals. Because of the potential for life-threatening cardiovascular complications [2,3], EhlersDanlos syndrome type IV, the rare vascular variant, is of particular concern to cardiac and vascular surgeons. Several genetic variants of EDS type IV exist, CARDIOVASCULAR SURGERY
DECEMBER 2002 VOL 10 NO 6
Figure 2 a and b: Arteriography showing dissected renal arteries with a severe postostial stenosis on the right side (arrows).
but all predominantly involve the skin, blood vessels, and intestine. Approximately 4% of EDS patients have the type IV variant [4]. The deficit in collagen type III the major structural component of blood vessels, results in a high incidence of cardiovascular complications in EDS type IV. The extreme fragility of the arteries is associated with the formation of multiple aneurysms, spontaneous rupture and dissection. All anatomic sites could be affected. 641
Fatal cardiovascular complications in a patient with Ehlers-Danlos syndrome type IV and dextrocardia: S. Jazayeri et al.
Figure 3 effusion.
Transoesophageal cardiac echography showed a pericardial
Spontaneous rupture of nonaneurysmal arteries is a classical vascular complication in this syndrome and occurs more frequently than the formation of aneurysms or dissection. The clinical presentation of peripheral arterial rupture includes localized pain, hematoma, and ecchymoses. Aortic and iliac artery ruptures often have catastrophic consequences with acute abdominal, back, or flank pain followed by cardiovascular collapse. Angiography should be employed only when dynamic CT scan, or magnetic resonance angiography cannot provide the required information because angiography was found to have morbidity and mortality rates of 16.7 and 5.6%, respectively per so [5]. Cardiac abnormalities such as mitral valve prolapse are reported to be common features of EDS, and it has been suggested that the majority of patients with type IV EDS will have cardiac involvement [6]. However, to the best of our knowledge the association of situs solitus with dextrocardy and Type IV EDS has never been reported in the literature. It should be mentioned that the grandfather of our patient had situs inversus and our patient was the only member of her family suffering from the type IV EDS and a cardiac abnormality. Nonvascular complications of EDS type IV include spontaneous perforation of the colon and intrapartum rupture of the uterus. Other obstetrical complications of EDS type IV are: premature delivery, uterine prolapse and vaginal and perineal tears. The risk of lethal complications in patients with EDS type IV appears to increase with pregnancy [7]. Pepin et al. in a recent survey of 100 female patients reported 12 deaths in 81 women who became pregnant [1]. The arterial tissues of patients with EDS type IV are extremely friable, therefore conventional arterial 642
Figure 4 a,b and c: Pulmonary X ray and transthoracic echography (four chamber incidence) demonstrated a situs solitus with dextrocardia (LV: left ventricule, LA: left atrium, RV: right ventricule, RA: right atrium).
repair with suture or graft is often not possible. Nonoperative management with bed rest, careful monitoring, and external compression, if feasible, may be the optimal therapy for patients with peripheral vascular hemorrhage who are hemodynamically stable. CARDIOVASCULAR SURGERY
DECEMBER 2002 VOL 10 NO 6
Fatal cardiovascular complications in a patient with Ehlers-Danlos syndrome type IV and dextrocardia: S. Jazayeri et al.
Ligation, when possible, has been the most successful operative treatment in those patients who require surgery [5]. When other operative therapy is required, minimal vessel dissection, with balloon catheter or tourniquet occlusion should be used. Primary arterial repair, if attempted, should be tensionless, using interrupted horizontal mattress sutures reinforced with Teflon pladgetts and biological glue [8]. Mattar et al. [9] conservatively treated a patient with pericardial and mediastinal hemorrhage with a positive outcome. In our case the presence of different localisations of arterial complications contraindicated the use of heparin which would have been necessary for the surgical repair cure of the ascending aorta using cardiopulmonary bypass. For Freeman et al. although operative mortality remains high (due to the tendency of vessels to tear with even minimal manipulation) mortality from major haemorrhage without surgical intervention seems to be even greater [5]. The prognosis in patients with type IV EDS is poor, even with modern diagnostic and therapeutic methods. Many patients present fatal vascular complications before their third decade of life. The mortality rate in patients with spontaneous hemorrhage has been reported to be 63% [10]. The maternal mortality rate for women with type IV EDS has been reported to be 25% with each pregnancy [11]. The case of our patient shows the difficulties that could be encountered when a patient with type IV EDS presents different localisations of arterial complications simultaneously. In our opinion, in these cases either surgical or nonoperative management could result in death. The lesson to be learned from our patient is that pregnancy can be a source of lethal
CARDIOVASCULAR SURGERY
DECEMBER 2002 VOL 10 NO 6
complications in these patients even several months after an uneventful delivery. Genetic counselling with molecular diagnosis is recommended for family members.
References 1. Pepin, M., Schwarze, U., Superti-Furga, A. et al. Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. New England Journal of Medicine, 2000, 342, 673–680. 2. De paepe, A. The Ehlers-Danlos syndrome: a heritable collagen disorder as cause of bleeding. Thrombosis and Hemostasis, 1996, 75, 379–386. 3. Pope, F. M., Nicholls, A. C., Narcisi, P. et al. Type III collagen mutations in Ehlers-Danlos syndrome, type IV and other related disorders. Clinical and Experimental Dermatology, 1988, 13, 285–302. 4. Beighton, P., Price, A., Lord, J. et al. Variation of Ehlers-Danlos syndrome: clinical, biochemical, haematological and chromosomal features of 100 patients. Annals of Rheumatic Diseases, 1969, 28, 228–245. 5. Freeman, R. K., Swegle, J. and Sise, M. J. The surgical complications of Ehlers-Danlos syndrome. American Surgery, 1996, 62, 869–873. 6. Dolan, A. L., Mishra, M. B., Chambers, J. B. et al. Clinical and echocardiographic survey of the Ehlers-Danlos syndrome. British Journal of Rheumatology, 1997, 36, 459–462. 7. Rudd, N. L., Nimrod, C., Holbrook, K. A. et al. Pregnancy complications in type IV Ehlers-Danlos syndrome. Lancet, 1983, 1, 50–53. 8. Ascione, R., Gomes, W. J., Bates, M. et al. Emergency repair of type A aortic dissection in type IV Ehlers-Danlos syndrome. Cardiovascular Surgery, 2000, 8, 75–78. 9. Mattar, S. G., Kumar, A. G. and Lumsden, A. B. Vascular complications in Ehlers-Danlos syndrome. American Surgery, 1994, 60, 827–831. 10. Cikrit, D. F., Miles, J. H. and Silver, D. Spontaneous arterial perforation: the Ehlers-Danlos specter. Journal of Vascular Surgery, 1987, 5, 248–255. 11. Rudd, N. L., Nimrod, C., Holbrook, K. A. et al. Pregnancy complications in type IV Ehlers-Danlos syndrome. Lancet, 1983, 1, 249–250. Paper accepted 1 May 2002
643
Cardiovascular Surgery, Vol. 10, No. 6, pp. 640–643, 2002 2002 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved. 0967-2109/02 $22.00
www.elsevier.com/locate/cardiosur
CASE REPORT Fatal cardiovascular complications in a patient with Ehlers-Danlos syndrome type IV and dextrocardia S. Jazayeri, M. C. Gomez, E. Tatou, M. Saleh, J. P. Parthiot, R. Brenot and M. David Service de Chirurgie Cardio-vasculaire, 2 Bd Mare´chal de Lattre de Tassigny, BP 1542, 21034 Dijon Cedex, France A report is presented of a 31 year female patient with Ehlers-Danlos syndrome type IV who presented a bilateral renal artery dissection and a hematoma of the ascending aorta simultaneously. She had had an uneventful delivery six months before. We also discovered a situs solitus with dextrocardia in this patient. These complications were managed conservatively. Unfortunately the patient died of a pulmonary infection and a multi-organ failure syndrome several days after her admission. 2002 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved. Keywords: Ehlers-Danlos syndrome, renal artery, dissection, dextrocardia, ascending aorta
Introduction Ehlers-Danlos syndrome (EDS) comprises more than 10 genetically, biochemically, and clinically distinct inherited disorders of collagen synthesis. EDS type IV or vascular type, is caused by structural defects in the proα1(III) chain of collagen type III encoded by COL3A1 [1]. This disorder produces defective type III collagen, the major structural component of blood vessels and viscera. As a result of this defect, EDS type IV patients often experience life-threatening cardio-vascular complications [2,3]. We report here a case of EDS type IV, associated with a congenital cardiac dextrocardia (situs solitus) in a young female patient with bilateral renal artery dissection and a hematoma of the ascending aorta, six months after an uneventful delivery.
Case report A 31 year female patient was admitted to our intensive care unit with a diagnosis of a retro-peritoneal Correspondence to: S. Jazayeri. Tel.: +33 380 293354 ; fax: +33 380 293385; e-mail: [email protected]
640
haemorrhage of unknown cause. Two hours before, she had been in profound shock with a slightly distended and painful abdomen. After rapid resuscitation by a mobile emergency unit at home she was admitted to a regional hospital. A CT scan was performed showing large left perirenal and retroperitoneal hematomas (Figure 1). The medical history listed EDS type IV diagnosed at age 14. Six months before she had had a baby after an elective caesarean at 33 weeks’ gestation. The delivery was uneventful, except for a thrombophlebitis of the left lower limb which was treated medically. On admission, she was conscious with a blood pressure of 130/70 mm Hg; heart rate 110 per min. Examination revealed mild abdominal tenderness. Her hematocrite was 30%. The CT scan showed a left peri-renal hematoma, probably due to the rupture or dissection of a left renal artery. The renal arteriography showed dysplasic renal arteries with images of dissection in both sides (Figure 2a and b). There was a severe post-ostial stenosis on the right side. The patient’s hemodynamic condition improved following blood volume replacement, and as her condition remained stable, a decision was made to conCARDIOVASCULAR SURGERY
DECEMBER 2002 VOL 10 NO 6
Fatal cardiovascular complications in a patient with Ehlers-Danlos syndrome type IV and dextrocardia: S. Jazayeri et al.
Figure 1 Computed tomography showing a left perirenal hematoma with a right kidney nonsecretant (arrows).
tinue managing her conservatively. The following day, a transthoracic and transoesophageal cardiac echography showed pericardial effusion (Figure 3) and a very localized hematoma of the ascending aorta with no sign of dissection. A situs solitus with dextrocardia was also diagnosed by pulmonary X ray and cardiac echography (Figure 4a,b and c). It was decided to drain this hemorrhage because of signs of compression on the right ventricle. Unfortunately 24 hours later, she presented spontaneous peri-hepatic and a rectus abdominalis hematomas. A subsequent spontaneous pneumothorax required a thoracic drainage. Finally, a pulmonary infection due to pseudomonas aeroginosa led to her death three days after her admission to hospital.
Discussion Ehlers-Danlos syndrome (EDS) is a heterogenous group of connective tissue disorders. More than ten types of this syndrome are now distinguished by a variety of clinical, biochemical, and genetic characteristics. The true prevalence of EDS remains unknown, it is estimated at about 1/150000 for all types of EDS. Of all the variants, types I–IV are the most common and comprise 95% of type-specific individuals. Because of the potential for life-threatening cardiovascular complications [2,3], EhlersDanlos syndrome type IV, the rare vascular variant, is of particular concern to cardiac and vascular surgeons. Several genetic variants of EDS type IV exist, CARDIOVASCULAR SURGERY
DECEMBER 2002 VOL 10 NO 6
Figure 2 a and b: Arteriography showing dissected renal arteries with a severe postostial stenosis on the right side (arrows).
but all predominantly involve the skin, blood vessels, and intestine. Approximately 4% of EDS patients have the type IV variant [4]. The deficit in collagen type III the major structural component of blood vessels, results in a high incidence of cardiovascular complications in EDS type IV. The extreme fragility of the arteries is associated with the formation of multiple aneurysms, spontaneous rupture and dissection. All anatomic sites could be affected. 641
Fatal cardiovascular complications in a patient with Ehlers-Danlos syndrome type IV and dextrocardia: S. Jazayeri et al.
Figure 3 effusion.
Transoesophageal cardiac echography showed a pericardial
Spontaneous rupture of nonaneurysmal arteries is a classical vascular complication in this syndrome and occurs more frequently than the formation of aneurysms or dissection. The clinical presentation of peripheral arterial rupture includes localized pain, hematoma, and ecchymoses. Aortic and iliac artery ruptures often have catastrophic consequences with acute abdominal, back, or flank pain followed by cardiovascular collapse. Angiography should be employed only when dynamic CT scan, or magnetic resonance angiography cannot provide the required information because angiography was found to have morbidity and mortality rates of 16.7 and 5.6%, respectively per so [5]. Cardiac abnormalities such as mitral valve prolapse are reported to be common features of EDS, and it has been suggested that the majority of patients with type IV EDS will have cardiac involvement [6]. However, to the best of our knowledge the association of situs solitus with dextrocardy and Type IV EDS has never been reported in the literature. It should be mentioned that the grandfather of our patient had situs inversus and our patient was the only member of her family suffering from the type IV EDS and a cardiac abnormality. Nonvascular complications of EDS type IV include spontaneous perforation of the colon and intrapartum rupture of the uterus. Other obstetrical complications of EDS type IV are: premature delivery, uterine prolapse and vaginal and perineal tears. The risk of lethal complications in patients with EDS type IV appears to increase with pregnancy [7]. Pepin et al. in a recent survey of 100 female patients reported 12 deaths in 81 women who became pregnant [1]. The arterial tissues of patients with EDS type IV are extremely friable, therefore conventional arterial 642
Figure 4 a,b and c: Pulmonary X ray and transthoracic echography (four chamber incidence) demonstrated a situs solitus with dextrocardia (LV: left ventricule, LA: left atrium, RV: right ventricule, RA: right atrium).
repair with suture or graft is often not possible. Nonoperative management with bed rest, careful monitoring, and external compression, if feasible, may be the optimal therapy for patients with peripheral vascular hemorrhage who are hemodynamically stable. CARDIOVASCULAR SURGERY
DECEMBER 2002 VOL 10 NO 6
Fatal cardiovascular complications in a patient with Ehlers-Danlos syndrome type IV and dextrocardia: S. Jazayeri et al.
Ligation, when possible, has been the most successful operative treatment in those patients who require surgery [5]. When other operative therapy is required, minimal vessel dissection, with balloon catheter or tourniquet occlusion should be used. Primary arterial repair, if attempted, should be tensionless, using interrupted horizontal mattress sutures reinforced with Teflon pladgetts and biological glue [8]. Mattar et al. [9] conservatively treated a patient with pericardial and mediastinal hemorrhage with a positive outcome. In our case the presence of different localisations of arterial complications contraindicated the use of heparin which would have been necessary for the surgical repair cure of the ascending aorta using cardiopulmonary bypass. For Freeman et al. although operative mortality remains high (due to the tendency of vessels to tear with even minimal manipulation) mortality from major haemorrhage without surgical intervention seems to be even greater [5]. The prognosis in patients with type IV EDS is poor, even with modern diagnostic and therapeutic methods. Many patients present fatal vascular complications before their third decade of life. The mortality rate in patients with spontaneous hemorrhage has been reported to be 63% [10]. The maternal mortality rate for women with type IV EDS has been reported to be 25% with each pregnancy [11]. The case of our patient shows the difficulties that could be encountered when a patient with type IV EDS presents different localisations of arterial complications simultaneously. In our opinion, in these cases either surgical or nonoperative management could result in death. The lesson to be learned from our patient is that pregnancy can be a source of lethal
CARDIOVASCULAR SURGERY
DECEMBER 2002 VOL 10 NO 6
complications in these patients even several months after an uneventful delivery. Genetic counselling with molecular diagnosis is recommended for family members.
References 1. Pepin, M., Schwarze, U., Superti-Furga, A. et al. Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. New England Journal of Medicine, 2000, 342, 673–680. 2. De paepe, A. The Ehlers-Danlos syndrome: a heritable collagen disorder as cause of bleeding. Thrombosis and Hemostasis, 1996, 75, 379–386. 3. Pope, F. M., Nicholls, A. C., Narcisi, P. et al. Type III collagen mutations in Ehlers-Danlos syndrome, type IV and other related disorders. Clinical and Experimental Dermatology, 1988, 13, 285–302. 4. Beighton, P., Price, A., Lord, J. et al. Variation of Ehlers-Danlos syndrome: clinical, biochemical, haematological and chromosomal features of 100 patients. Annals of Rheumatic Diseases, 1969, 28, 228–245. 5. Freeman, R. K., Swegle, J. and Sise, M. J. The surgical complications of Ehlers-Danlos syndrome. American Surgery, 1996, 62, 869–873. 6. Dolan, A. L., Mishra, M. B., Chambers, J. B. et al. Clinical and echocardiographic survey of the Ehlers-Danlos syndrome. British Journal of Rheumatology, 1997, 36, 459–462. 7. Rudd, N. L., Nimrod, C., Holbrook, K. A. et al. Pregnancy complications in type IV Ehlers-Danlos syndrome. Lancet, 1983, 1, 50–53. 8. Ascione, R., Gomes, W. J., Bates, M. et al. Emergency repair of type A aortic dissection in type IV Ehlers-Danlos syndrome. Cardiovascular Surgery, 2000, 8, 75–78. 9. Mattar, S. G., Kumar, A. G. and Lumsden, A. B. Vascular complications in Ehlers-Danlos syndrome. American Surgery, 1994, 60, 827–831. 10. Cikrit, D. F., Miles, J. H. and Silver, D. Spontaneous arterial perforation: the Ehlers-Danlos specter. Journal of Vascular Surgery, 1987, 5, 248–255. 11. Rudd, N. L., Nimrod, C., Holbrook, K. A. et al. Pregnancy complications in type IV Ehlers-Danlos syndrome. Lancet, 1983, 1, 249–250. Paper accepted 1 May 2002
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