Radiation-Associated Valvular Disease* Robert G. Carlson, M.D.;t Wdliam R. Mayfield, M.D.;t
Sigurd Normann, M.D., Ph.D.;§ and james A. Alexantkr, M.D.,
F.C.C.E~
The prevalence of radiation-associated cardiac disease is increasing due to prolonged survival following mediastinal irradiation. Side effects of radiation include pericarditis, accelerated coronary artery disease, myocardial 6brosis and valvular inju~ We evaluated the cases of three young patients with evidence of signi6cant valvular disease following mediastinal irradiation. One patient underwent the 6rst reported successful aortic and mitral valve replacement for radiation-associated valvular disease (RAVD) as well as concurrent coronary artery revascularization. A review of the literature revealed 35 reported cases of RAVD, with only one successful case of valve replacement that was limited to the aortic valve. Asymptomatic RAVD is diagnosed 11.5 years after mediastinal irradiation compared
with 16.5 years for symptomatic patients, emphasizing that long-term follow-up is important for patients receiving mediastinal irradiation. This study de6nes a continuum of valvular disease following radiation that begins with mild asymptomatic valvular thickening and progresses to severe valvular 6brosis with hemodynamic compromise requiring surgical intervention. (Chest 1991; 99:538-45)
injury after mediastinal irradiation includes C ardiac acute pericarditis,I.2 chronic pericarditis with or
symptomatic valvular dysfunction.
without effusion,3.5-7 accelerated arteriosclerosis of the coronary arteries,8-16 myocardial fibrosis, 10-12,16-19 valvular dysfunction,2,6,7,9.9»-28 and conduction abnormalities.I.10.12 Although some authors disagree that mediastinal irradiation causes occlusive disease in the coronary arteries,16 acute myocardial infarction and sudden death have occurred in very young patients following mediastinal irradiation. 8 ,10.12 In addition, symptomatic valvular dysfunction following radiation has been cited infrequently, with only ten reported cases. 9,20,22.24,27-28 In the last two decades, no reports (to our knowledge) have identified the coexistence of symptomatic radiation-associated coronary artery disease and bivalvular dysfunction in the .aortic and mitral positions. In this report we present three patients with radiation-associated valvular disease (RAVD) of whom two had concurrent coronary artery disease. In addition, we describe the first successfully combined coronary revascularization and bivalvular replacement in a patient with radiation-associated heart disease. Based on this experience and a review of the literature, we conclude that RAVD represents a continuum, progressing from asymptomatic valvular thickening to
*From the Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Florida, College of Medicine, Gainesville. tSurgicai Resident. iAssistant Professor of Surgery. § Professor of Pathology. 'Professor and Chief, Division of Cardiothoracic Surgery. Manuscript received April 18; revision accepted July 30.
538
AR = aortic regurgitation; BBB = bundle branch block; circumftex artery; IMA = internal mammary artery; LAD = left anterior descending artery; LVEDP left ventricular end diastolic pressure; MR mitral regurgitation; NYHA = New York Heart Association; PAP = pulmonary artery pressure; RAVD = radiation associated valvular disease; RCA = right coronary artery
cGy = centigray; ex = left
=
=
CASE REpORTS CASE
1
Aortic and Mitral Valve Replacement with Coronary Artery Bypass Grafting FoUowing Mediastinal Irradiation
An 18-year-old white male subject was in good health until March 1974 when he was diagnosed as having embryonal cell carcinoma of the testicle. He underwent unilateral adrenalectomy and right radical retroperitoneal node dissection with evidence of nodal metastasis. Postoperatively~ he received chemotherapy (chlorambucil, dactinomycin, and methotrexate) and simultaneous supervoltage radiation therapy using the inverted Y format to the mantle, paraaortic, and femoral regions with a total abdominal dose of 4,200 cGy. The supradiaphragmatic lymph nodes were treated with 4~100 cGy to the mediastinum and anterior and posterior parts of the chest. The left supraclavicular region received 4000 cGy. Four years after radiation therapy, at age 22 years, he experienced chest pain and suffered an acute inferior wall myocardial infarction. He smoked approximately one pack a day for five years; his serum cholesterol value was 167 mg/dl and triglyceride level was 86 mgldl. The patient denied having rheumatic fever as a child. Cardiac catheterization revealed total occlusion ofthe right coronary artery (RCA), 80 percent proximal stenosis in the left anterior descending coronary artery (LAD), 80 percent proximal stenosis of a diagonal branch, and 50 percent stenosis of the left circum8ex artery (CX) distal to the first marginal branch. Apical akinesis and distinct hypokinesis of the septum were noted. The right ventricular pressure was modestly elevated and there was no evidence of valvular abnormalities. Three months later he underwent a fourvessel coronary artery bypass to the LAD, RCA, second marginal circum8ex, and diagonal coronary arteries. Severe scarring of the posterior myocardial wall in the distribution of the RCA was noted and the artery appeared scarred but not atherosclerotic. Scarring was noted in the proximal segment of the LAD with a nonnalThere was thickening of the epicardium appearing vessel distall~ adjacent to the aorta, aortic root, and pulmonary artery with extension onto the right ventricle. The pericardium was neither thickened nor adherent to the heart. Radiation-associated Valvular Disease (Carlson 8t aJ)
FI(:llRE 1. Coronary arterio~ram in case 1 demonstratin!t a saphenous vt>in graftleadin~ totht> ohtust> marginal artery. Arrow indicates site of hi~h-grade ostial lesions of the saphenous vein ~raft at the aortic anastomosis. Nine years later, at a~e 32 years. he presented with mild C')Jl~estive heart failure semndary to mitral regurgitation (MR), which improved with medical therapy. Cardiac catheteri7~'ltion revealed patent saphenous vein grafts to tht> RCA and LAD hut a 95 percent occlusion of the distal posterior descendin~ artery and a diffusely diseased CX. In addition. there was 3 + MR. 1 + aortic re~ur/.,';tation (AR), and pulmonary hypertension with a pulmonary artery pressure (PAP) of 60/34 mm H~ (mean = 46), and a left ventricular enddiastolic pressure (LVEDP) of22 nUll Hg. Four months later, in January 1989. he had a non-Q wave myocardial infarction that was followed hy persistent fatigue. Recatheterization revealed moderate to severe MR. moderate AR, aortic valve stenosis with a 20 mm gradient. and moderate left ventric'ular dysfunction (LVEDP = 30 mm H~ and PAP = 65130, and mean = 47 mm H~). Coronary artery disease had pro~ressed
FIGURE 3. Radiation-associated valvular disease in a 27-year-old man 9 years after mediastinal irradiation (case 1). Photomicro~raph demonstrates extensive fihrosis of the mitral valve (Masson trichrome stain, original ma~nification x 307). the obtuse mar~inal vein graft had a high-~rade ostial lesion at the aortic anastomosis (Fi~ 1). Echocardiography mnfirmed MR and AR with associated aortic valve thickenin~ and restricted movement (Fi!t 2). An electrocardiogram (ECG) revealed inmmplete left bundle branch block (BBB) with left atrial enlar!tement and left ventricular hypertrophy witb a strain paltern. He then underwent aortic and mitral valve replacement with a 21 mm St Jude aortic valve and a 25 mm St Jude mitral valve. A vein patch angioplasty was performed on the obtuse marwnal !traft. Intraoperative findings included severe fibrosis of the entire mediastinum and pericardium. The mitral valve was stenotic and had malted chordae tendinae with subvalvular nodules. The mitral valve leaflets were markedly thickened with extensive fibrosis (Fig 3). The aortic valve leaflets were fibrotic with focal dystrophic calcification. Histolowcally, the pericardium was thickened and composed of dense fibrous connective tissue with focal calcification. The patient's postoperative c'mrse was unremarkable and in li>lIow-up evaluations he has done well and exhibits New York Heart Association (NYHA) class 1 exercise tolerance. CASE
2
Coronary Artery RevasculariZl,ti(m in a lbtient with Ri,diati(massociated Coronary Artery and lJIlvular Disease
FIGURE 2. Two-dimensional echocardio~ram of case 1 showin!t the parasternal axis. Tht> aortic' valve (AV) is thickent>d and exhihits restricted movement. The mitral valve (MV) is thickened. Ao = aorta; LV = left ventricle; RV = right ventricle.
A 33-year-old woman with no history of ci~arelte smokin~ or hypercholesterolemia was in !tood health until a!te 19 years, when she noted a right supraclavicular mass. Stage IlA Hod!tkin's disease, nodular sclerosin!t type, was dia!tllosed after extensive evaluation. She underwent radiotherapy usin!t the Linae 2 and 3 technique, with a total of 3,700 cGy to the mantle and 3,700 cGy to the parasupraclavicular boost with 300 aortic and splenic portals. A ri~t c,'Gy by Betatron 10 MeV was performed. Thirteen years later she had normal results of a workup for intermittent chest pain. However, one year thereafter, she had a non-Q wave myocardial infarction. Cardiac catheterization revealed CHEST I 99 I 3 I MARCH, 1991
539
/
alrial hiopsy sp"dnwn re\'(·all·d exlt'lIsive myol.'yle \'acuolar chan~e. increaspd Ihickl'nin~ of the epicardium and endocardium. and interstitial and pt'rivascular fihrosis (Fi~ 5). A 11'1'1 venlricular biopsy slweinlt'n n'v('alpd m
Sigurd Normann, M.D., Ph.D.;§ and james A. Alexantkr, M.D.,
F.C.C.E~
The prevalence of radiation-associated cardiac disease is increasing due to prolonged survival following mediastinal irradiation. Side effects of radiation include pericarditis, accelerated coronary artery disease, myocardial 6brosis and valvular inju~ We evaluated the cases of three young patients with evidence of signi6cant valvular disease following mediastinal irradiation. One patient underwent the 6rst reported successful aortic and mitral valve replacement for radiation-associated valvular disease (RAVD) as well as concurrent coronary artery revascularization. A review of the literature revealed 35 reported cases of RAVD, with only one successful case of valve replacement that was limited to the aortic valve. Asymptomatic RAVD is diagnosed 11.5 years after mediastinal irradiation compared
with 16.5 years for symptomatic patients, emphasizing that long-term follow-up is important for patients receiving mediastinal irradiation. This study de6nes a continuum of valvular disease following radiation that begins with mild asymptomatic valvular thickening and progresses to severe valvular 6brosis with hemodynamic compromise requiring surgical intervention. (Chest 1991; 99:538-45)
injury after mediastinal irradiation includes C ardiac acute pericarditis,I.2 chronic pericarditis with or
symptomatic valvular dysfunction.
without effusion,3.5-7 accelerated arteriosclerosis of the coronary arteries,8-16 myocardial fibrosis, 10-12,16-19 valvular dysfunction,2,6,7,9.9»-28 and conduction abnormalities.I.10.12 Although some authors disagree that mediastinal irradiation causes occlusive disease in the coronary arteries,16 acute myocardial infarction and sudden death have occurred in very young patients following mediastinal irradiation. 8 ,10.12 In addition, symptomatic valvular dysfunction following radiation has been cited infrequently, with only ten reported cases. 9,20,22.24,27-28 In the last two decades, no reports (to our knowledge) have identified the coexistence of symptomatic radiation-associated coronary artery disease and bivalvular dysfunction in the .aortic and mitral positions. In this report we present three patients with radiation-associated valvular disease (RAVD) of whom two had concurrent coronary artery disease. In addition, we describe the first successfully combined coronary revascularization and bivalvular replacement in a patient with radiation-associated heart disease. Based on this experience and a review of the literature, we conclude that RAVD represents a continuum, progressing from asymptomatic valvular thickening to
*From the Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Florida, College of Medicine, Gainesville. tSurgicai Resident. iAssistant Professor of Surgery. § Professor of Pathology. 'Professor and Chief, Division of Cardiothoracic Surgery. Manuscript received April 18; revision accepted July 30.
538
AR = aortic regurgitation; BBB = bundle branch block; circumftex artery; IMA = internal mammary artery; LAD = left anterior descending artery; LVEDP left ventricular end diastolic pressure; MR mitral regurgitation; NYHA = New York Heart Association; PAP = pulmonary artery pressure; RAVD = radiation associated valvular disease; RCA = right coronary artery
cGy = centigray; ex = left
=
=
CASE REpORTS CASE
1
Aortic and Mitral Valve Replacement with Coronary Artery Bypass Grafting FoUowing Mediastinal Irradiation
An 18-year-old white male subject was in good health until March 1974 when he was diagnosed as having embryonal cell carcinoma of the testicle. He underwent unilateral adrenalectomy and right radical retroperitoneal node dissection with evidence of nodal metastasis. Postoperatively~ he received chemotherapy (chlorambucil, dactinomycin, and methotrexate) and simultaneous supervoltage radiation therapy using the inverted Y format to the mantle, paraaortic, and femoral regions with a total abdominal dose of 4,200 cGy. The supradiaphragmatic lymph nodes were treated with 4~100 cGy to the mediastinum and anterior and posterior parts of the chest. The left supraclavicular region received 4000 cGy. Four years after radiation therapy, at age 22 years, he experienced chest pain and suffered an acute inferior wall myocardial infarction. He smoked approximately one pack a day for five years; his serum cholesterol value was 167 mg/dl and triglyceride level was 86 mgldl. The patient denied having rheumatic fever as a child. Cardiac catheterization revealed total occlusion ofthe right coronary artery (RCA), 80 percent proximal stenosis in the left anterior descending coronary artery (LAD), 80 percent proximal stenosis of a diagonal branch, and 50 percent stenosis of the left circum8ex artery (CX) distal to the first marginal branch. Apical akinesis and distinct hypokinesis of the septum were noted. The right ventricular pressure was modestly elevated and there was no evidence of valvular abnormalities. Three months later he underwent a fourvessel coronary artery bypass to the LAD, RCA, second marginal circum8ex, and diagonal coronary arteries. Severe scarring of the posterior myocardial wall in the distribution of the RCA was noted and the artery appeared scarred but not atherosclerotic. Scarring was noted in the proximal segment of the LAD with a nonnalThere was thickening of the epicardium appearing vessel distall~ adjacent to the aorta, aortic root, and pulmonary artery with extension onto the right ventricle. The pericardium was neither thickened nor adherent to the heart. Radiation-associated Valvular Disease (Carlson 8t aJ)
FI(:llRE 1. Coronary arterio~ram in case 1 demonstratin!t a saphenous vt>in graftleadin~ totht> ohtust> marginal artery. Arrow indicates site of hi~h-grade ostial lesions of the saphenous vein ~raft at the aortic anastomosis. Nine years later, at a~e 32 years. he presented with mild C')Jl~estive heart failure semndary to mitral regurgitation (MR), which improved with medical therapy. Cardiac catheteri7~'ltion revealed patent saphenous vein grafts to tht> RCA and LAD hut a 95 percent occlusion of the distal posterior descendin~ artery and a diffusely diseased CX. In addition. there was 3 + MR. 1 + aortic re~ur/.,';tation (AR), and pulmonary hypertension with a pulmonary artery pressure (PAP) of 60/34 mm H~ (mean = 46), and a left ventricular enddiastolic pressure (LVEDP) of22 nUll Hg. Four months later, in January 1989. he had a non-Q wave myocardial infarction that was followed hy persistent fatigue. Recatheterization revealed moderate to severe MR. moderate AR, aortic valve stenosis with a 20 mm gradient. and moderate left ventric'ular dysfunction (LVEDP = 30 mm H~ and PAP = 65130, and mean = 47 mm H~). Coronary artery disease had pro~ressed
FIGURE 3. Radiation-associated valvular disease in a 27-year-old man 9 years after mediastinal irradiation (case 1). Photomicro~raph demonstrates extensive fihrosis of the mitral valve (Masson trichrome stain, original ma~nification x 307). the obtuse mar~inal vein graft had a high-~rade ostial lesion at the aortic anastomosis (Fi~ 1). Echocardiography mnfirmed MR and AR with associated aortic valve thickenin~ and restricted movement (Fi!t 2). An electrocardiogram (ECG) revealed inmmplete left bundle branch block (BBB) with left atrial enlar!tement and left ventricular hypertrophy witb a strain paltern. He then underwent aortic and mitral valve replacement with a 21 mm St Jude aortic valve and a 25 mm St Jude mitral valve. A vein patch angioplasty was performed on the obtuse marwnal !traft. Intraoperative findings included severe fibrosis of the entire mediastinum and pericardium. The mitral valve was stenotic and had malted chordae tendinae with subvalvular nodules. The mitral valve leaflets were markedly thickened with extensive fibrosis (Fig 3). The aortic valve leaflets were fibrotic with focal dystrophic calcification. Histolowcally, the pericardium was thickened and composed of dense fibrous connective tissue with focal calcification. The patient's postoperative c'mrse was unremarkable and in li>lIow-up evaluations he has done well and exhibits New York Heart Association (NYHA) class 1 exercise tolerance. CASE
2
Coronary Artery RevasculariZl,ti(m in a lbtient with Ri,diati(massociated Coronary Artery and lJIlvular Disease
FIGURE 2. Two-dimensional echocardio~ram of case 1 showin!t the parasternal axis. Tht> aortic' valve (AV) is thickent>d and exhihits restricted movement. The mitral valve (MV) is thickened. Ao = aorta; LV = left ventricle; RV = right ventricle.
A 33-year-old woman with no history of ci~arelte smokin~ or hypercholesterolemia was in !tood health until a!te 19 years, when she noted a right supraclavicular mass. Stage IlA Hod!tkin's disease, nodular sclerosin!t type, was dia!tllosed after extensive evaluation. She underwent radiotherapy usin!t the Linae 2 and 3 technique, with a total of 3,700 cGy to the mantle and 3,700 cGy to the parasupraclavicular boost with 300 aortic and splenic portals. A ri~t c,'Gy by Betatron 10 MeV was performed. Thirteen years later she had normal results of a workup for intermittent chest pain. However, one year thereafter, she had a non-Q wave myocardial infarction. Cardiac catheterization revealed CHEST I 99 I 3 I MARCH, 1991
539
/
alrial hiopsy sp"dnwn re\'(·all·d exlt'lIsive myol.'yle \'acuolar chan~e. increaspd Ihickl'nin~ of the epicardium and endocardium. and interstitial and pt'rivascular fihrosis (Fi~ 5). A 11'1'1 venlricular biopsy slweinlt'n n'v('alpd m
