Cardiac and cerebral manifestations of the antiphospholipid syndrome

Summary

Aim: To describe cardiac and cerebral manifestations in eight patients with the antiphospholipid syndrome and a review of the literature. Patients and Methods: We studied eight patients with the antiphospholipid syndrome (APS) with either cardiac or cerebral or both manifestations. All patients fulfilled the proposed classification criteria for the APS according to the SSC of the ISTH. One patient died and had an autopsy. Results: Five of the eight patients had coronary artery disease with either thrombotic coronary occlusions or high grade stenosis, of which three patients had an occlusion of the left main artery or LAD. As valvular lesions have been described in association with the APS it is to note that three patients had thickening either of the mitral valve or aortic valve and one patient had an aortic valve replacement. The other two patients presented with a history of cerebral infarction. One of these patients also had a prior history of myocardial infarction, whereas the other patient had a history of aortic valve endocarditis. Conclusion: The APS can be associated with cardiac and cerebral manifestations. Acute thrombotic vessel occlusion presents as one of the most frequent vascular manifestations. Also valvular lesions can be associated with the APS.

Zusammenfassung

Ziel: Die Beschreibung kardialer und zerebraler Manifestationen in acht Patienten mit der Diagnose eines Antiphospholipid-Syndroms mit einem Literaturüberblick. Patienten und Methoden: Wir untersuchten acht Patienten mit einem Antiphospholipid-Syndrom (APS) mit kardialen oder zerebralen Manifestationen. Alle Patienten erfüllten die bekannten Klassifikationskriterien für ein APS gemäß der SSC der ISTH. Ein Patient verstarb und wurde autopsiert. Ergebnisse: Fünf der acht Patienten hatten eine koronare Herzerkrankung mit entweder thrombotischem Koronarverschluss oder hochgradigen Stenosen. Drei Patienten hatten einen Verschluss des linken Hauptstammes oder der LAD. Klappenerkrankungen sind bei Patienten mit APS beschrieben worden. Drei der acht Patienten zeigten Verdickungen der Mitraloder Aortenklappe. Ein Patient hatte einen Aortenklappenersatz. Zwei weitere Patienten erlitten einen Hirninfarkt. Einer dieser Patienten hatte ebenfalls eine Vorgeschichte eines Myokardinfarktes, der andere Patient einer Aortenklappen-Endokarditis. Schlussfolgerung: Das APS kann einhergehen mit kardialen und zerebralen Manifestationen. Akute thrombotische Gefäßverschlüsse sind die häufigsten vaskulären Manifestationen. Auch Veränderungen an Herzklappen können mit einem APS assoziiert sein.

Keywords

Antiphospholipid syndrome - coronary artery disease - myocardial infarction - valvular disease - cerebral manifestations

Schlüsselwörter

Antiphospholipid-Syndrom - koronare Herzerkrankung - Myokardinfarkt - Klappenerkrankung - zerebrale Manifestationen

• References

• 1 Brandt JT, Triplett DA, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH. Thromb Haemost 1995; 74: 1185-90.
• 2 Schmidt R, Scheuermann EH, Viertel A, Geiger H, Scharrer I. Antiphospholipid antibody syndrome. Med Klin 1999; 94: 93-100.
• 3 Asherson RA, Khamashta MA, Ordi-Ros J, Derksen RH, Machin SJ, Barquinero J, Outt HH, Harris EN, Vilardell-Torres M, Hughes GR. The “primary”; antiphospholipid syndrome: major clinical and serological features. Medicine (Baltimore) 1989; 68: 366-74.
• 4 Silver RM, Draper ML, Scott JR, Lyon JL, Reading J, Branch DW. Clinical consequences of antiphospholipid antibodies: an historic cohort study. Obstet Gynecol 1994; 83: 372-7.
• 5 McNeil HP, Chesterman CN, Krilis SA. Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol 1991; 49: 193-280.
• 6 Laraki R, Bletry O, Wechsler B, Piette JC, de Zuttere D, Godeau P. The heart and antiphospholipid antibodies. Personal experience and review of the literature. Rev Med Interne 1996; 17: 46-57.
• 7 Shortell CK, Ouriel K, Green RM, Condemi JJ, DeWeese JA. Vascular disease in the antiphospholipid syndrome: a comparison with the patient population with atherosclerosis. J Vasc Surg 1992; 15: 158-65 discussion 165-6.
• 8 Love PE, Santoro SA. Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders. Prevalence and clinical significance. Ann Intern Med 1990; 112: 682-98.
• 9 Asherson RA, Hackett D, Gharavi AE, Harris EN, Kennedy HG, Hughes GR. Pulmonary hypertension in systemic lupus erythematosus: a report of three cases. J Rheumatol 1986; 13: 416-20.
• 10 Asherson RA, Oakley CM. Pulmonary hypertension and systemic lupus erythematosus [published erratum appears in J Rheumatol 1986 Aug;13(4): 840]. J Rheumatol 1986; 13: 1-5.
• 11 Weber M, Hayem G, DeBandt M, Palazzo E, Roux S, Kahn MF, Meyer O. The family history of patients with primary or secondary antiphospholipid syndrome (APS) [In Process Citation]. Lupus 2000; 9: 258-63.
• 12 McNeil HP, Gavaghan TP, Krilis SA, Geczy AF, Chesterman CN. HLA-DR antigens and anticardiolipin antibodies [letter]. Clin Exp Rheumatol 1990; 8: 425-6.
• 13 Ames PR, Tommasino C, Iannaccone L, Brillante M, Cimino R, Brancaccio V. Coagulation activation and fibrinolytic imbalance in subjects with idiopathic antiphospholipid antibodies – a crucial role for acquired free protein S deficiency. Thromb Haemost 1996; 76: 190-4.
• 14 Rand JH, Wu XX. Antibody-mediated disruption of the annexin-V antithrombotic shield: a new mechanism for thrombosis in the antiphospholipid syndrome. Thromb Haemost 1999; 82: 649-55.
• 15 Gabrielli F, Alcini E, Di Prima MA, Mazzacurati G, Masala C. Cardiac valve involvement in systemic lupus erythematosus and primary antiphospholipid syndrome: lack of correlation with antiphospholipid antibodies. Int J Cardiol 1995; 51: 117-26.
• 16 Gabrielli F, Alcini E, Prima MA, Lucifero A, Masala C. Cardiac involvement in connective tissue diseases and primary antiphospholipid syndrome: echocardiographic assessment and correlation with antiphospholipid antibodies. Acta Cardiol 1996; 51: 425-39.
• 17 Gleason CB, Stoddard MF, Wagner SG, Longaker RA, Pierangeli S, Harris EN. A comparison of cardiac valvular involvement in the primary antiphospholipid syndrome versus anticardiolipin-negative systemic lupus erythematosus. Am Heart J 1993; 125: 1123-9.
• 18 Ducceschi V, Sarubbi B, Iacono A. Primary antiphospholipid syndrome and cardiovascular disease. Eur Heart J 1995; 16: 441-5.
• 19 Takeuchi S, Obayashi T, Toyama J. Primary antiphospholipid syndrome with acute myocardial infarction recanalised by PTCA. Heart 1998; 79: 96-8.
• 20 Umesan CV, Kapoor A, Nityanand S, Tiwari S, Sinha N. Recurrent acute coronary events in a patient with primary antiphospholipid syndrome: successful management with intracoronary stenting [letter]. Int J Cardiol 1999; 71: 99-102.
• 21 Hofgartner F, Bader A, Burkle V, Schmeiser T, Bosch A, Sigel H. Right ventricular thrombus after pacemaker implantation in a patient with secondary antiphospholipid syndrome. Dtsch Med Wochenschr 1998; 123: 12-6.
• 22 Cervera R, Khamashta MA, Font J, Reyes PA, Vianna JL, Lopez-Soto A, Amigo MC, Asherson RA, Azqueta M, Pare C. et al. High prevalence of significant heart valve lesions in patients with the ›primary‹ antiphospholipid syndrome. Lupus 1991; 1: 43-7.
• 23 Brenner B, Blumenfeld Z, Markiewicz W, Reisner SA. Cardiac involvement in patients with primary antiphospholipid syndrome. J Am Coll Cardiol 1991; 18: 931-6.
• 24 Galve E, Ordi J, Barquinero J, Evangelista A, Vilardell M, Soler-Soler J. Valvular heart disease in the primary antiphospholipid syndrome. Ann Intern Med 1992; 116: 293-8.
• 25 Garcia-Torres R, Amigo MC, de la Rosa A, Moron A, Reyes PA. Valvular heart disease in primary antiphospholipid syndrome (PAPS): clinical and morphological findings. Lupus 1996; 5: 56-61.
• 26 Levine SR, Brey RL. Neurological aspects of antiphospholipid antibody syndrome. Lupus 1996; 5: 347-53.
• 27 Kenet G, Sadetzki S, Murad H, Martinowitz U, Rosenberg N, Gitel S, Rechavi G, Inbal A. Factor V Leiden and antiphospholipid antibodies are significant risk factors for ischemic stroke in children. Stroke 2000; 31: 1283-8.
• 28 Levine SR, Brey RL, Sawaya KL, Salowich-Palm L, Kokkinos J, Kostrzema B, Perry M, Havstad S, Carey J. Recurrent stroke and thrombo-occlusive events in the antiphospholipid syndrome. Ann Neurol 1995; 38: 119-24.
• 29 Hughes GR. Hughes syndrome: antiphospholipid syndrome. J R Coll Physicians Lond 1998; 32: 260-4.
• 30 Angelini L, Zibordi F, Zorzi G, Nardocci N, Caporali R, Ravelli A, Martini A. Neurological disorders, other than stroke, associated with antiphospholipid antibodies in childhood. Neuropediatrics 1996; 27: 149-53.
• 31 Agah R, Rice L, Winikates J. Fatal cerebral venous thrombosis as the initial manifestation of the antiphospholipid syndrome. Clin Neurol Neurosurg 1996; 98: 189-91.
• 32 Christopher R, Nagaraja D, Dixit NS, Narayanan CP. Anticardiolipin antibodies: a study in cerebral venous thrombosis. Acta Neurol Scand 1999; 99: 121-4.
• 33 Asherson RA, Mercey D, Phillips G, Sheehan N, Gharavi AE, Harris EN, Hughes GR. Recurrent stroke and multi-infarct dementia in systemic lupus erythematosus: association with antiphospholipid antibodies. Ann Rheum Dis 1987; 46: 605-11.
• 34 Hilker R, Thiel A, Geisen C, Rudolf J. Cerebral blood flow and glucose metabolism in multiinfarct-dementia related to primary antiphospholipid antibody syndrome [In Process Citation]. Lupus 2000; 9: 311-6.
• 35 Asherson RA, Piette JC. The catastrophic antiphospholipid syndrome 1996: acute multiorgan failure associated with antiphospholipid antibodies: a review of 31 patients. Lupus 1996; 5: 414-7.
• 36 Hamsten A, Norberg R, Bjorkholm M, de Faire U, Holm G. Antibodies to cardiolipin in young survivors of myocardial infarction: an association with recurrent cardiovascular events. Lancet 1986; 1: 113-6.
• 37 Harpaz D, Glikson M, Sidi Y, Hod H. Successful thrombolytic therapy for acute myocardial infarction in a patient with the antiphospholipid antibody syndrome. Am Heart J 1991; 122: 1492-5.
• 38 Vaarala O, Manttari M, Manninen V, Tenkanen L, Puurunen M, Aho K, Palosuo T. Anti-cardiolipin antibodies and risk of myocardial infarction in a prospective cohort of middle-aged men. Circulation 1995; 91: 23-7.
• 39 Kattwinkel N, Villanueva AG, Labib SB, Aretz HT, Walek JW, Burns DL, Klenz JT. Myocardial infarction caused by cardiac microvasculopathy in a patient with the primary antiphospholipid syndrome. Ann Intern Med 1992; 116: 974-6.
• 40 Farsi A, Domeneghetti MP, Fedi S, Capanni M, Giusti B, Marcucci R, Giurlani L, Prisco D, Passaleva A, Gensini GF, Abbate R. High prevalence of anti-beta2 glycoprotein I antibodies in patients with ischemic heart disease. Autoimmunity 1999; 30: 93-8.
• 41 Afek A, Shoenfeld Y, Manor R, Goldberg I, Ziporen L, George J, Polak-Charcon S, Amigo MC, Garcia-Torres R, Segal R, Kopolovic J. Increased endothelial cell expression of alpha3beta1 integrin in cardiac valvulopathy in the primary (Hughes) and secondary antiphospholipid syndrome. Lupus 1999; 8: 502-7.
• 42 Vaarala O. Atherosclerosis in SLE and Hughes syndrome [editorial]. Lupus 1997; 6: 489-90.
• 43 Vaarala O. Antiphospholipid antibodies and atherosclerosis. Lupus 1996; 5: 442-7.
• 44 Vaarala O. Antibodies to oxidised LDL [In Process Citation]. Lupus 2000; 9: 202-5.
• 45 Amengual O, Atsumi T, Khamashta MA, Hughes GR. Clinical significance of anti-beta 2-glycoprotein I antibodies. Ann Med Interne (Paris) 1996; 147 (Suppl. 01) 15-7.
• 46 Amengual O, Atsumi T, Khamashta MA, Tinahones F, Hughes GR. Autoantibodies against oxidized low-density lipoprotein in antiphospholipid syndrome. Br J Rheumatol 1997; 36: 964-8.
• 47 Amengual O, Atsumi T, Khamashta MA, Bertolaccini ML, Hughes GR. IgG2 restriction of anti-beta2-glycoprotein I as the basis for the association between IgG2 anticardiolipin antibodies and thrombosis in the antiphospholipid syndrome: comment on the article by Sammaritano et al. [letter; comment]. Arthritis Rheum 1998; 41: 1513-5.
• 48 Brown JH, Doherty CC, Allen DC, Morton P. Fatal cardiac failure due to myocardial micro-thrombi in systemic lupus erythematosus. Br Med J (Clin Res Ed) 1988; 296: 1505.
• 49 Murphy JJ, Leach IH. Findings at necropsy in the heart of a patient with anticardiolipin syndrome. Br Heart J 1989; 62: 61-4.
• 50 Kaplan SD, Chartash EK, Pizzarello RA, Furie RA. Cardiac manifestations of the antiphospholipid syndrome. Am Heart J 1992; 124: 1331-8.
• 51 Airoldi ML, Eid O, Tosetto C, Meroni PL. Post-partum dilated cardiomyopathy in antiphospholipid positive woman. Lupus 1996; 5: 247-50.
• 52 Coudray N, de Zuttere D, Bletry O, Piette JC, Wechsler B, Godeau P, Pourny JC, Lecarpentier Y, Chemla D. M mode and Doppler echocardiographic assessment of left ventricular diastolic function in primary antiphospholipid syndrome. Br Heart J 1995; 74: 531-5.
• 53 Khamashta MA, Cervera R, Asherson RA, Font J, Gil A, Coltart DJ, Vazquez JJ, Pare C, Ingelmo M, Oliver J. et al. Association of antibodies against phospholipids with heart valve disease in systemic lupus erythematosus [see comments]. Lancety 1990; 335: 1541-4.
• 54 Nihoyannopoulos P, Gomez PM, Joshi J, Loizou S, Walport MJ, Oakley CM. Cardiac abnormalities in systemic lupus erythematosus. Association with raised anticardiolipin antibodies [see comments]. Circulation 1990; 82: 369-75.
• 55 Galve E OJ, Candell-Riera J, Permanyer-Miralda G, Vilardell M, Soler-Soler J. Valvular heart disease in systemic lupus erythematosus (letter). N Engl J Med 1989; 320: K739-741.
• 56 Galve E, Candell-Riera J, Pigrau C, Permanyer-Miralda G, Garcia-Del-Castillo H, Soler-Soler J. Prevalence, morphologic types, and evolution of cardiac valvular disease in systemic lupus erythematosus. N Engl J Med 1988; 319: 817-23.
• 57 Nesher G, Ilany J, Rosenmann D, Abraham AS. Valvular dysfunction in antiphospholipid syndrome: prevalence, clinical features, and treatment. Semin Arthritis Rheum 1997; 27: 27-35.
• 58 Ford SE, Lillicrap D, Brunet D, Ford P. Thrombotic endocarditis and lupus anticoagulant. A pathogenetic possibility for idiopathic ›rheumatic type‹ valvular heart disease. Arch Pathol Lab Med 1989; 113: 350-3.
• 59 Derumeaux G, Lenormand C, Borg JY, Levesque H, Tron F, Letac B. Prevalence and description of cardiac involvements in primary antiphospholipid syndrome. Arch Mal Coeur Vaiss 1992; 85: 1811-8.
• 60 Harris EN, Gharavi AE, Asherson RA, Boey ML, Hughes GR. Cerebral infarction in systemic lupus: association with anticardiolipin antibodies. Clin Exp Rheumatol 1984; 2: 47-51.
• 61 Mackworth-Young CG, Loizou S, Walport MJ. Primary antiphospholipid syndrome: features of patients with raised anticardiolipin antibodies and no other disorder. Ann Rheum Dis 1989; 48: 362-7.
• 62 Asherson RA, Hughes GR. Antiphospholipid antibodies and chorea [letter]. J Rheumatol 1988; 15: 377-9.
• 63 D’Alton JG, Preston DN, Bormanis J, Green MS, Kraag GR. Multiple transient ischemic attacks, lupus anticoagulant and verrucous endocarditis. Stroke 1985; 16: 512-4.
• 64 Hughes GR. The antiphospholipid syndrome. Lupus 1996; 5: 345-6.
• 65 Montalban J, Codina A, Ordi J, Vilardell M, Khamashta MA, Hughes GR. Antiphospholipid antibodies in cerebral ischemia. Stroke 1991; 22: 750-3.
• 66 Verro P, Levine SR, Tietjen GE. Cerebrovascular ischemic events with high positive anticardiolipin antibodies. Stroke 1998; 29: 2245-53.
• 67 Barbut D, Borer JS, Wallerson D, Ameisen O, Lockshin M. Anticardiolipin antibody and stroke: possible relation of valvular heart disease and embolic events [see comments]. Cardiology 1991; 79: 99-109.
• 68 Nomura H, Hirashima Y, Endo S, Takaku A. Anticardiolipin antibody aggravates cerebral vasospasm after subarachnoid hemorrhage in rabbits. Stroke 1998; 29: 1014-8 discussion 1018-9.
• 69 Hirashima Y, Endo S, Kurimoto M, Tsukamoto E, Takaku A. Platelet-activating factor and antiphospholipid antibodies in subarachnoid haemorrhage. Acta Neurochir 1994; 128: 144-9.
• 70 Espinola-Zavaleta N, Vargas-Barron J, Colmenares-Galvis T, Cruz-Cruz F, Romero-Cardenas A, Keirns C, Amigo MC. Echocardiographic evaluation of patients with primary antiphospholipid syndrome. Am Heart J 1999; 137: 973-8.