Ghadri, Jelena-Rima

Kaufmann, Philipp

Landmesser, Ulf

Lüscher, Thomas

Templin, Christian

Wyss, Christophe

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CLINICAL CORRESPONDENCESevere left main coronary stenosis and mitral regurgitationin a young female patient without cardiovascular risk factors14 years after mediastinal radiation therapyChristian Templin • Jelena-Rima Ghadri •Christophe Wyss • Thomas F. Lu¨scher •Philipp Kaufmann • Ulf LandmesserReceived: 11 September 2009 / Accepted: 9 December 2009 / Published online: 29 December 2009 Springer-Verlag 2009A 29-year-old female with a medical history of mediastinalradiation therapy for B-cell non-Hodgkin lymphoma14 years ago (total irradiation dose: 36 Gy) was admittedto our hospital with symptoms of chest pain and dyspnoea.Echocardiography showed a thickening of the mitral valvewith a medium to severe regurgitation. A myocardial per-fusion scintigraphy demonstrated anterior wall ischemia(Fig. 1) and a cardiac computer tomography scan demon-strated a non-calcified stenosis in the left main bifurcationwith an approximately 50% luminal narrowing and a 70–90% non-calcified ostial stenosis in the left anteriordescending artery. Coronary angiography was performedand demonstrated a significant distal bifurcation stenosis ofthe left main coronary artery (70%), a 90% ostial stenosisof the left circumflex coronary artery and an ostial stenosisof the left anterior descending artery (Fig. 2a, b). Therewas no evidence for atherosclerotic disease in other vas-cular regions in this patient. The patient had no cardio-vascular risk factors. Laboratory studies showed totalcholesterol of 4.4 mmol/l, HDL cholesterol of 1.4 mmol/l,and LDL cholesterol of 4.1 mmol/l. Erythrocyte sedimen-tation rate (ESR) and C-reactive protein were within thenormal range. Results of serologic antibody studies forsystemic lupus erythematosus or systemic vasculitis wereunremarkable. Therefore, late radiation-induced coronaryand valvular heart disease was considered as the mostlikely diagnosis. The patient underwent coronary arterybypass grafting using both internal thoracic arteries andmitral valve repair was performed. The postoperativecourse was uneventful.Of note, left main stenosis in young patients in whichclassical risk factors of atherosclerosis are lacking may beattributed to several other causes, such as being secondaryto vasculitis syndromes (Takayasu arteritis; Kawasakisyndrome). Coronary arterial involvement in Takayasu’sarteritis has been described with a low incidence, i.e.approximately 10% of cases [6]. However, in particular thelack of inflammatory activation (as indicated by normalCRP and ESR) or symptoms such as fever suggested to usthat coronary artery involvement of a Takayasu arteritis isnot a very likely diagnosis in this patient. The lack of signsof inflammatory activity or aneurysmatic lesions of thecoronary arteries argued against the Kawasaki syndrome asa likely diagnosis in this patient that does occur almostexclusively in children.Because this patient had no laboratory signs and noclinical symptoms of inflammatory activation or manifes-tations nor other angiographic abnormalities, and given theknown history of Hodgkin lymphoma and mediastinalradiation therapy, a postmediastinal radiation-inducedcoronary artery disease is highly suggestive.Notably, exposure of the heart to ionizing radiation isconsidered to be associated with an increased risk ofdeveloping coronary artery and valvular heart disease, thatmay occur 3 up to 30 years after radiation therapy [3, 4]. Acommon localization of coronary lesions after radiotherapyis at the ostial or proximal segment, with a distal disease-free vasculature [8]. Aortic valve stenosis and left-sidedvalvular regurgitation have been most frequently associatedC. Templin (&)  C. Wyss  T. F. Lu¨scher  P. Kaufmann U. LandmesserDepartment of Cardiology, Cardiovascular Center,University Hospital Zu¨rich, Raemistr. 100,8091 Zurich, Switzerlande-mail: Christian.Templin@usz.chJ.-R. GhadriGeneral Internal Medicine, Department of Medicine,University Hospital Zu¨rich, Zurich, Switzerland123Clin Res Cardiol (2010) 99:199–201DOI 10.1007/s00392-009-0103-4with radiation therapy [4, 5]. Coronary bypass grafting isfrequently performed in these patients given recent obser-vations of an unacceptably high rate of restenosis after cor-onary stenting in excess of 80% at least with the use of baremetal stents [10]. There are no studies or case reportsavailable at present about the impact of drug-eluting stentson coronary restenosis in patients with radiation-inducedcoronary disease. However, one would assume that theresults might be more favorable. In our patient, given theanatomy and location of coronary stenoses and accompa-nying valvular heart disease, we did not consider coronarystenting as an optimal revascularization strategy. Notably,there has been concern regarding potential radiation damageto the internal thoracic arteries [9]. A recent registry from theMayo Clinic, however, suggests a better outcome in patientsafter mediastinal radiation therapy receiving internal tho-racic artery grafts rather than venous bypass grafting [1].Overall, the outcome of coronary bypass surgery may be lessfavorable in patients after mediastinal radiation [1], and aclose follow-up should be recommended.It is estimated that 5.5–12% of patients receivingmediastinal radiation develop radiation-induced coronaryartery disease with a latency of onset of 3–30 years [7].Although the pathogenesis of radiation-induced coronaryartery disease is complex and not fully understood, it isassociated with marked adventitial fibrosis and thickening,medial thinning and destruction and a greater calcium andlipid content within intimal plaques [11]. It is suggestivethat leaflets of valves may undergo fibrotic changes with orwithout calcification [2]. However, the exact pathogenesisof radiation-induced coronary disease has not been studiedin detail. At present, this will intensely examined in theCARDIORISK project, an integrated database funded bythe European Commission in the 7th Framework Program(http://www.cardiorisk.eu/index.php) that will hopefullylead to novel approaches to prevent this important latecomplication of mediastinal radiotherapy.This report suggests that doctors should be highly alertfor symptoms of coronary disease that can be very severe,even in young female patients after radiation therapy.Fig. 1 Tc-99m MIBI myocardial perfusion SPECT study with bullyeye images at rest and at peak stress revealed a perfusion defect of theanterior wallFig. 2 Coronary angiography, showing distal bifurcation stenosis ofthe left main coronary artery (70%), and an ostial stenosis of the leftcircumflex coronary artery (90%)200 Clin Res Cardiol (2010) 99:199–201123Based on current data, a long-term follow-up for earlydetection of coronary or valvular heart disease needs to beconsidered in patients after mediastinal radiotherapy.References1. Brown ML, Schaff HV, Sundt TM (2008) Conduit choice forcoronary artery bypass grafting after mediastinal radiation.J Thorac Cardiovasc Surg 136(5):1167–11712. Carlson RG, Mayfield WR, Normann S, Alexander JA (1991)Radiation-associated valvular disease. Chest 99(3):538–5453. Glanzmann C, Kaufmann P, Jenni R, Hess OM, Huguenin P(1998) Cardiac risk after mediastinal irradiation for Hodgkin’sdisease. Radiother Oncol 46(1):51–624. Hull MC, Morris CG, Pepine CJ, Mendenhall NP (2003) Valvulardysfunction and carotid, subclavian, and coronary artery diseasein survivors of Hodgkin lymphoma treated with radiation therapy.JAMA 290(21):2831–28375. Lund MB, Ihlen H, Voss BM, Abrahamsen AF, Nome O,Kongerud J, Stugaard M, Forfang K (1996) Increased risk ofheart valve regurgitation after mediastinal radiation for Hodg-kin’s disease: an echocardiographic study. Heart 75(6):591–5956. Makino N, Orita Y, Takeshita A, Nakamura M, Matsui K,Tokunaga K (1982) Coronary arterial involvement in Takayasu’sdisease. Jpn Heart J 23(6):1007–10137. Miltenyi Z, Keresztes K, Garai I, Edes I, Galajda Z, Toth L, IllesA (2004) Radiation-induced coronary artery disease in Hodgkin’sdisease. Cardiovasc Radiat Med 5(1):38–438. Rademaker J, Scho¨der H, Ariaratnam NS, Strauss HW, YahalomJ, Steingart R, Oeffinger KC (2008) Coronary artery disease afterradiation therapy for Hodgkin’s lymphoma: coronary CT angi-ography findings and calcium scores in nine asymptomaticpatients. Am J Roentgenol 191(1):32–379. Renner SM, Massel D, Moon BC (1999) Mediastinal irradiation:a risk factor for atherosclerosis of the internal thoracic arteries.Can J Cardiol 15:597–60010. Schomig K, Ndrepepa G, Mehilli J, Pache J, Kastrati A, SchomigA (2007) Thoracic radiotherapy in patients with lymphoma andrestenosis after coronary stent placement. Catheter CardiovascInterv 70(3):359–36511. Virmani R, Farb A, Carter AJ, Jones RM (1999) Pathology ofradiation-induced coronary artery disease in human and pig.Cardiovasc Radiat Med 1(1):98–101Clin Res Cardiol (2010) 99:199–201 201123

Severe left main coronary stenosis and mitral regurgitation in a young female patient without cardiovascular risk factors 14years after mediastinal radiation therapy

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Severe left main coronary stenosis and mitral regurgitation in a young female patient without cardiovascular risk factors 14years after mediastinal radiation therapy

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