case report Wien Klin Wochenschr DOI 10.1007/s00508-014-0505-9
Radiotherapy-induced concomitant coronary artery stenosis and mitral valve disease Mehmet Kadri Akboga · Ahmet Akyel · Asife Şahinarslan · Atiye Çengel
Received: 11 July 2013 / Accepted: 14 January 2014 © Springer-Verlag Wien 2014
Summary Radiotherapy is extensively used in the treatment of Hodgkin’s disease. One of its untoward effects is on heart. Coronary arteries and heart valves can be adversely affected from radiotherapy. However, co-existence of both conditions is very rare. In this report, we present a patient with Hodgkin’s disease who developed both coronary artery stenosis and severe mitral valve regurgitation after radiotherapy. Keywords Radiotherapy · Coronary artery disease · Mitral valve
Strahlentherapie induziertes gleichzeitiges Auftreten einer Stenose der Koronararterien und einer Erkrankung der Mitralklappen Zusammenfassung Bei der Behandlung des Morbus Hodgkin wird eine ausgiebige Strahlentherapie angewandt. Koronararterien und Mitralklappen können – als unerwünschte Nebenwirkung – dadurch geschädigt werden. Dass beide zugleich beeinträchtigt werden, ist allerdings extrem selten. Im vorliegenden Fallbericht beschreiben wir den Verlauf eines Patienten mit Morbus Hodgkin, der nach Strahlentherapie sowohl eine Stenose
M. K. Akboga, MD () Department of Cardiology, Ministry of Health Etimesgut State Hospital, Ankara, Turkey e-mail: [email protected] A. Akyel, MD Department of Cardiology, DıS¸kapı Education and Research Hospital, Ankara, Turkey Assoc. Prof. A. S¸ ahinarslan, MD · Prof. A. Çengel, MD Department of Cardiology, Gazi University Medical Faculty, Ankara, Turkey
13
der Koronararterien als auch eine schwere Mitralinsuffizienz entwickelte. Schlüsselwörter Morbus Hodgkin · Strahlentherapie · Koronare Herzkrankheit · Mitralklappen
Introduction The heart with its vessels and valves is vulnerable to untoward effects of radiotherapy, which is extensively used in the treatment of Hodgkin’s disease (HD). Although these complications are seen rarely, they can cause devastating clinical situations for patients. Herein, we present a patient with HD who developed both coronary artery stenosis and severe mitral valve regurgitation after radiotherapy.
Case report A 26-year-old male patient presented to our emergency department with complaint of dyspnea. On admission, his clinical picture was compatible with decompensated heart failure. Patient was devoid of any cardiovascular risk factor. His electrocardiogram revealed poor R-wave progression pattern in anterior leads. In his medical history, he was diagnosed with stage IVB nodular sclerosing synctial variant-type HD on February 2007. He was treated with six cures of chemotherapy. However, as the disease was resistant to chemotherapy, 36-Gy radiotherapy was given to mediastinal area on December 2008. Furthermore, autologous hematopoietic stem cell transplantation has also been performed. The echocardiography was completely normal before chemoradiotherapy. On admission, he was still on immunosuppressive therapy for HD. At his routine control on May 2011, a new mass was detected at the appendix of the left atrium. Car-
Radiotherapy-induced concomitant coronary artery stenosis and mitral valve disease
1
case report
diac magnetic resonance imaging had revealed that the mass was not in relation with mitral valve. He was operated for this mass, and the cell culture produced Aspergillus fumigatus. He was treated with voriconazole and, until present admission, he was doing well. Patient was compensated with intravenous diuretic treatment. His thoracic computed tomography (CT) revealed typical signs of previous thoracic irradiation. Echocardiography revealed normal ejection fraction and severe mitral regurgitation (MR) due to restrictive motion in posterior mitral valve leaflet (Fig. 1). Because of development of new heart failure and absence of severe MR on his past echocardiograms, coronary angiography was performed. Coronary angiography revealed significant stenosis on the left anterior descending artery (LAD) with TIMI II coronary flow (Fig. 2). Cardiac catheterization findings were negative for constrictive pericarditis. Surgery was suggested for LAD lesion and mitral valve
Fig. 1 Severe mitral regurgitation after radiotherapy
disease. However, the patient refused the operation, and a bare metal stent was implanted to the LAD. On his firstyear control, the patient was doing well with a functional status of NYHA class I. However, the degree of MR was the same (grade 3) with restrictive motion in posterior mitral valve leaflet.
Discussion In this report, we presented an HD patient who had concomitant coronary artery disease and mitral valve disease most possibly due to radiotherapy. Considering the history of mediastinal radiotherapy, young age of the patient, absence of any cardiovascular risk factor, and presence of typical radiotherapy-induced lesions on thoracal CT, we thought that the main insult for both LAD stenosis and MR was radiotherapy. Deleterious effects of radiation can be seen in different body sites. For example, mediastinal fibrosis, isolated coronary artery stenosis, or isolated heart valve disease due to radiotherapy has been reported previously in the literature [1–2]. Hull et al. [2] reported a retrospective analysis of 415 HD patients who were treated with radiotherapy. In their analysis, nearly 10 % of patients developed coronary artery disease at a median time of 9 years after treatment, and 6.2 % of them developed significant valvular disease at a median time of 22 years [2]. Similarly, Lund et al. [3] reported that valvular disease due to radiotherapy might be more frequent than we have assumed. Cavendish et al. [4] reported that coronary artery and multiple arch vessel disease can concomitantly occur in patients with a previous history of radiotherapy. According to these reports, it can be proposed that untoward effects of radiotherapy can be seen in various tissue sites. In mechanistic point of view, fibrointimal hyperplasia due to intimal injury and secondary lipid deposition have been proposed mechanisms for coronary stenosis [5]. Exact mechanism of valvular heart disease due to radiotherapy is still not known. In our patient, three different reasons may play a role in the development of MR: (1) ischemia due to coronary heart disease [6], (2) radiation-induced fibrosis and restriction on mitral valve [7], and (3) constrictive pathology of pericardium [8]. As we excluded constrictive physiology on cardiac catheterization, first two possibilities remained as possible mechanisms for MR. Although the LAD was revascularized and ischemia was resolved, severity of MR did not reduce. This is why we suggested the second mechanism as potential pathogenic insult for MR in our patient. The time interval between the radiotherapy and overt disease is another unclear issue. However, existence of these pathologies may be more frequent than we assume. This is why symptomatologic and echocardiographic follow-up is very important in HD patients, especially in patients who have received mediastinal radiotherapy.
Fig. 2 Severe stenosis in left anterior descending artery
2 Radiotherapy-induced concomitant coronary artery stenosis and mitral valve disease
13
case report Conflict of interest The authors declare that there is no actual or potential conflict of interest in relation to this article.
References 1. Om A, Ellahham S, Vetrovec GW. Radiation-induced coronary artery disease (Review). Am Heart J. 1992 Dec;124(6):1598–602. 2. Hull MC, Morris CG, Pepine CJ, et al. Valvular dysfunction and carotid, subclavian and coronary artery disease in survivors of Hodgkin lymphoma treated with radiation therapy. JAMA. 2003;290:2831–7. 3. Lund MB, Ihlen H, Voss BM, et al. Increased risk of heart valve regurgitation after mediastinal radiation for Hodgkin’s disease: an echocardiographic study. Heart. 1996;75(6):591–5.
13
4. Cavendish JJ, Berman BJ, Schnyder G, Kerber C, Mahmud E, Turi ZG, Blanchard D, Tsimikas S. Concomitant coronary and multiple arch vessel stenoses in patients treated with external beam radiation: pathophysiological basis and endovascular treatment. Catheter Cardiovasc Interv. 2004 Jul;62(3):385–90. 5. Gold H. Production of arteriosclerosis in the rat. Effect of x-ray and a high-fat diet. Arch Pathol. 1961;71:268–73. 6. Grossi EA, Goldberg JD, LaPietra A, et al. Ischemic mitral valve reconstruction and replacement: comparison of long-term survival and complications. J Thorac Cardiovasc Surg. 2001;122(6):1107–24. 7. Carlson RG, Mayfield WR, Normann S, et al. Radiation associated valvular disease. Chest. 1991;99:538–45. 8. Orzan F, Brusca A. Radiation-induced constrictive pericarditis. Associated cardiac lesions, therapy and follow-up. G Ital Cardiol. 1994;24(7):817–23.
Radiotherapy-induced concomitant coronary artery stenosis and mitral valve disease
3
Radiotherapy-induced concomitant coronary artery stenosis and mitral valve disease Mehmet Kadri Akboga · Ahmet Akyel · Asife Şahinarslan · Atiye Çengel
Received: 11 July 2013 / Accepted: 14 January 2014 © Springer-Verlag Wien 2014
Summary Radiotherapy is extensively used in the treatment of Hodgkin’s disease. One of its untoward effects is on heart. Coronary arteries and heart valves can be adversely affected from radiotherapy. However, co-existence of both conditions is very rare. In this report, we present a patient with Hodgkin’s disease who developed both coronary artery stenosis and severe mitral valve regurgitation after radiotherapy. Keywords Radiotherapy · Coronary artery disease · Mitral valve
Strahlentherapie induziertes gleichzeitiges Auftreten einer Stenose der Koronararterien und einer Erkrankung der Mitralklappen Zusammenfassung Bei der Behandlung des Morbus Hodgkin wird eine ausgiebige Strahlentherapie angewandt. Koronararterien und Mitralklappen können – als unerwünschte Nebenwirkung – dadurch geschädigt werden. Dass beide zugleich beeinträchtigt werden, ist allerdings extrem selten. Im vorliegenden Fallbericht beschreiben wir den Verlauf eines Patienten mit Morbus Hodgkin, der nach Strahlentherapie sowohl eine Stenose
M. K. Akboga, MD () Department of Cardiology, Ministry of Health Etimesgut State Hospital, Ankara, Turkey e-mail: [email protected] A. Akyel, MD Department of Cardiology, DıS¸kapı Education and Research Hospital, Ankara, Turkey Assoc. Prof. A. S¸ ahinarslan, MD · Prof. A. Çengel, MD Department of Cardiology, Gazi University Medical Faculty, Ankara, Turkey
13
der Koronararterien als auch eine schwere Mitralinsuffizienz entwickelte. Schlüsselwörter Morbus Hodgkin · Strahlentherapie · Koronare Herzkrankheit · Mitralklappen
Introduction The heart with its vessels and valves is vulnerable to untoward effects of radiotherapy, which is extensively used in the treatment of Hodgkin’s disease (HD). Although these complications are seen rarely, they can cause devastating clinical situations for patients. Herein, we present a patient with HD who developed both coronary artery stenosis and severe mitral valve regurgitation after radiotherapy.
Case report A 26-year-old male patient presented to our emergency department with complaint of dyspnea. On admission, his clinical picture was compatible with decompensated heart failure. Patient was devoid of any cardiovascular risk factor. His electrocardiogram revealed poor R-wave progression pattern in anterior leads. In his medical history, he was diagnosed with stage IVB nodular sclerosing synctial variant-type HD on February 2007. He was treated with six cures of chemotherapy. However, as the disease was resistant to chemotherapy, 36-Gy radiotherapy was given to mediastinal area on December 2008. Furthermore, autologous hematopoietic stem cell transplantation has also been performed. The echocardiography was completely normal before chemoradiotherapy. On admission, he was still on immunosuppressive therapy for HD. At his routine control on May 2011, a new mass was detected at the appendix of the left atrium. Car-
Radiotherapy-induced concomitant coronary artery stenosis and mitral valve disease
1
case report
diac magnetic resonance imaging had revealed that the mass was not in relation with mitral valve. He was operated for this mass, and the cell culture produced Aspergillus fumigatus. He was treated with voriconazole and, until present admission, he was doing well. Patient was compensated with intravenous diuretic treatment. His thoracic computed tomography (CT) revealed typical signs of previous thoracic irradiation. Echocardiography revealed normal ejection fraction and severe mitral regurgitation (MR) due to restrictive motion in posterior mitral valve leaflet (Fig. 1). Because of development of new heart failure and absence of severe MR on his past echocardiograms, coronary angiography was performed. Coronary angiography revealed significant stenosis on the left anterior descending artery (LAD) with TIMI II coronary flow (Fig. 2). Cardiac catheterization findings were negative for constrictive pericarditis. Surgery was suggested for LAD lesion and mitral valve
Fig. 1 Severe mitral regurgitation after radiotherapy
disease. However, the patient refused the operation, and a bare metal stent was implanted to the LAD. On his firstyear control, the patient was doing well with a functional status of NYHA class I. However, the degree of MR was the same (grade 3) with restrictive motion in posterior mitral valve leaflet.
Discussion In this report, we presented an HD patient who had concomitant coronary artery disease and mitral valve disease most possibly due to radiotherapy. Considering the history of mediastinal radiotherapy, young age of the patient, absence of any cardiovascular risk factor, and presence of typical radiotherapy-induced lesions on thoracal CT, we thought that the main insult for both LAD stenosis and MR was radiotherapy. Deleterious effects of radiation can be seen in different body sites. For example, mediastinal fibrosis, isolated coronary artery stenosis, or isolated heart valve disease due to radiotherapy has been reported previously in the literature [1–2]. Hull et al. [2] reported a retrospective analysis of 415 HD patients who were treated with radiotherapy. In their analysis, nearly 10 % of patients developed coronary artery disease at a median time of 9 years after treatment, and 6.2 % of them developed significant valvular disease at a median time of 22 years [2]. Similarly, Lund et al. [3] reported that valvular disease due to radiotherapy might be more frequent than we have assumed. Cavendish et al. [4] reported that coronary artery and multiple arch vessel disease can concomitantly occur in patients with a previous history of radiotherapy. According to these reports, it can be proposed that untoward effects of radiotherapy can be seen in various tissue sites. In mechanistic point of view, fibrointimal hyperplasia due to intimal injury and secondary lipid deposition have been proposed mechanisms for coronary stenosis [5]. Exact mechanism of valvular heart disease due to radiotherapy is still not known. In our patient, three different reasons may play a role in the development of MR: (1) ischemia due to coronary heart disease [6], (2) radiation-induced fibrosis and restriction on mitral valve [7], and (3) constrictive pathology of pericardium [8]. As we excluded constrictive physiology on cardiac catheterization, first two possibilities remained as possible mechanisms for MR. Although the LAD was revascularized and ischemia was resolved, severity of MR did not reduce. This is why we suggested the second mechanism as potential pathogenic insult for MR in our patient. The time interval between the radiotherapy and overt disease is another unclear issue. However, existence of these pathologies may be more frequent than we assume. This is why symptomatologic and echocardiographic follow-up is very important in HD patients, especially in patients who have received mediastinal radiotherapy.
Fig. 2 Severe stenosis in left anterior descending artery
2 Radiotherapy-induced concomitant coronary artery stenosis and mitral valve disease
13
case report Conflict of interest The authors declare that there is no actual or potential conflict of interest in relation to this article.
References 1. Om A, Ellahham S, Vetrovec GW. Radiation-induced coronary artery disease (Review). Am Heart J. 1992 Dec;124(6):1598–602. 2. Hull MC, Morris CG, Pepine CJ, et al. Valvular dysfunction and carotid, subclavian and coronary artery disease in survivors of Hodgkin lymphoma treated with radiation therapy. JAMA. 2003;290:2831–7. 3. Lund MB, Ihlen H, Voss BM, et al. Increased risk of heart valve regurgitation after mediastinal radiation for Hodgkin’s disease: an echocardiographic study. Heart. 1996;75(6):591–5.
13
4. Cavendish JJ, Berman BJ, Schnyder G, Kerber C, Mahmud E, Turi ZG, Blanchard D, Tsimikas S. Concomitant coronary and multiple arch vessel stenoses in patients treated with external beam radiation: pathophysiological basis and endovascular treatment. Catheter Cardiovasc Interv. 2004 Jul;62(3):385–90. 5. Gold H. Production of arteriosclerosis in the rat. Effect of x-ray and a high-fat diet. Arch Pathol. 1961;71:268–73. 6. Grossi EA, Goldberg JD, LaPietra A, et al. Ischemic mitral valve reconstruction and replacement: comparison of long-term survival and complications. J Thorac Cardiovasc Surg. 2001;122(6):1107–24. 7. Carlson RG, Mayfield WR, Normann S, et al. Radiation associated valvular disease. Chest. 1991;99:538–45. 8. Orzan F, Brusca A. Radiation-induced constrictive pericarditis. Associated cardiac lesions, therapy and follow-up. G Ital Cardiol. 1994;24(7):817–23.
Radiotherapy-induced concomitant coronary artery stenosis and mitral valve disease
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