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Recurrent Syncope Following Radiation Therapy
Recurrent Syncope Following Radiation Therapy SIDDHARTH MUKERJI, MD; ROSHAN PATEL, MD; ATUL KHASNIS, MD; CHOTIKORN KHUNNAWAT, MD; RANJAN K. THAKUR, MD
ABSTRACT: This case report describes a 51-year-old man who presented with syncope. His electrocardiogram showed an abnormally long pause and the electrophysiology study revealed a prolonged H-V interval. This was attributed to the radiation therapy he received to the chest. He was successfully treated with implanta-
tion of a permanent pacemaker. This case highlights this rare complication of radiation-induced conduction system disease and management of this potentially lifethreatening condition. KEY INDEXING TERMS: Radiation; Fibrosis; Syncope; Pacemaker. [Am J Med Sci 2006;331(6):325–328.]
C
cantly abnormal for a 1.6-second pause during the first minute of recovery. The baseline electrocardiogram recorded is shown in Figure 1. Cardiac catheterization revealed 50% to 60% stenosis of the proximal and middle left circumflex coronary artery and 30% stenosis of the left anterior descending coronary artery. The right coronary artery showed mild diffuse narrowing. The measured left ventricular ejection fraction was found to be 40%. In view of recurrent syncope and abnormal pause on the exercise electrocardiogram (ECG), the patient underwent an electrophysiology study to look for possible underlying conduction system disease. The intracardiac electrogram (Figure 2) shows an A-H interval of 72 msec and H-V interval of 92 msec, with baseline cycle length of 680 msec. Corrected sinus node recovery time was normal, as was atrial and ventricular stimulation for induction of tachyarrhythmias. We decided to implant a dual-chamber pacemaker in view of the increased H-V interval. The patient has done well since the procedure and has had no recurrence of symptoms.
onduction system disease as a complication of thoracic irradiation is rarely reported in the literature. We present a case of a patient with this condition and discuss the mechanisms and management of radiation-induced fibrosis of the cardiac conduction system. Case Report A 51-year-old obese man presented with recurrent syncope; he had had four episodes over the preceding 3 months. There was no associated palpitations, shortness of breath, or chest pain. His past medical history included type 2 diabetes mellitus, hypertension, asthma, and carcinoid syndrome. He had received three courses of radiation therapy to the chest for the bronchial carcinoid. Review of symptoms was negative for symptoms of recurrence of carcinoid syndrome. Physical examination of the cardiovascular system was unremarkable. Holter monitoring did not show any evidence of tachy- or bradyarrhythmias. Magnetic resonance angiography of the vertebrobasilar vessels demonstrated mild stenosis of the midbasilar artery. Electroencephalography did not show any evidence of seizure-like activity. An exercise stress test was negative for myocardial ischemia but was signifi-
From the Sparrow Health System, Division of Cardiology, Michigan State University, East Lansing, Michiagan. Submitted August 17, 2005; accepted in revised form February 24, 2006. Correspondence: Ranjan K. Thakur, MD, The Thoracic and Cardiovascular Institute, Ingham Regional Medical Center, 405 West Greenlawn Suite 400, Lansing, Michigan 48910 (E-mail: [email protected]). THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Discussion Cardiac damage secondary to thoracic irradiation was first observed the 1930s.1 However, documentation of these events did not occur until the 1960s. This complication of radiation therapy was initially reported in patients receiving thoracic irradiation for Hodgkin’s disease. Irradiation of the chest has been reported to damage all three layers of the heart as well as the conduction system and great vessels. Of these, pericardial disease is the most frequently reported.1–3 325
Recurrent Syncope Following Radiation Therapy
Figure 1. Surface electrocardiogram showing a prolonged PR interval (200 ms) with a left anterior fascicular block (LAFB) and a complete right bundle branch block (RBBB).
Conduction disturbances occur uncommonly by comparison.4 Radiation-induced tissue damage is mediated by free electrons. Although the damage caused by radiation is most toxic to rapidly proliferating cells, slowly dividing cells can also be affected.5 The combination of apoptosis and microvascular destruction leads to ischemic cellular loss and fibrosis.6,7 In our patient, both the mild coronary artery disease and conduction system disease may have been secondary to radiation. The presence of risk factors (obesity, hypertension, type 2 diabetes mellitus) probably contributed to the accelerated atherosclerosis. We believe the most likely cause of heart block was degeneration of the His-Purkinje system secondary to radiation. Radiation therapy primarily affects the anteriormost components of the intracardiac conduction system. In addition, the damage is progressive,8 which is consistent with the ECG findings of right bundle branch block with left anterior fascicular block in our patient. The amount of radiation influences the development of complications. Although the other detrimental effects of radiation therapy have a dose-based relationship (25– 40 Gy), this has not been established for cardiac conduction disturbances.1,4,6 The latent period before the development of various complications ranges from 6 months to 30 years.1,5 Cardiac arrhythmias and conduction disturbances usually occur years after radiation expo326
sure. They should be differentiated from the repolarization abnormalities that are transient and seen shortly after radiation therapy.6 The most serious of the conduction abnormalities include sick sinus syndrome and second- or third-degree heart block.5,7–11,12 Our patient developed heart block after approximately 8 years. His ECG showed first-degree atrioventricular block with a complete right bundle branch block and left anterior fascicular block. A review of literature suggests that infranodal blocks occur more frequently than intrinsic atrioventricular nodal blocks after radiation therapy.5–7,12 The prolonged H-V interval (92 msec) recorded in our patient is also consistent with the infranodal conduction system degeneration (Figure 2). The incidence of bundle branch block increases with aging as a result of increasing fibrosis and calcification of the fibrous skeleton of the heart. In a study carried out by Eriksson et al.13 1% of men aged 50 years developed progressive degenerative disease of the conducting system, as opposed to 17% of subjects at age 80. In view of this, it is unlikely that degeneration fibrosis of the conducting system was the primary cause of heart block in our patient. Implantation of a permanent pacemaker for this condition is beneficial, as observed in most studies.7,10,12,14 Our patient was symptomatic with evidence of diffuse infranodal conduction system disJune 2006 Volume 331 Number 6
Mukerji et al
Figure 2. Intracardiac recording showing normal A-H interval (72 msec) and a prolonged H-V interval of 92 msec (normal, 35–55 msec). The numbers seen along lead II represent heart rate at the respective cycle length (numbers indicated along RVA). HIS, His bundle; HRA, high right atrium; RVA, right ventricular apex.
ease. Hence, we proceeded to implant a permanent pacemaker. Conclusion Fibrosis of the conduction system of the heart is a known but relatively uncommon complication of thoracic irradiation. With the advent of the pacemaker, this potentially fatal condition is amenable to treatment. References 1. Veinot JP, Edwards WD. Pathology of radiation-induced heart disease: a surgical and autopsy study of 27 cases. Hum Pathol 1996;27:766–73. 2. Fajardo LF, Stewart JR, Cohn KE. Morphology of radiation-induced heart disease. Arch Pathol 1968;86:512–9. 3. Schultz-Hector S. Radiation-induced heart disease: review of experimental data on dose response and pathogenesis. Int J Radiat Biol 1992;61:149–60.
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
4. Adams MJ, Lipshultz SE, Schwartz C, et al. Radiation associated cardiovascular disease: manifestations and management. Semin Radiat Oncol 2003;13:346–56. 5. Haimovitz-Friedman A, Kan CC, Ehleiter D, et al. Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J Exp Med 1994;180:525–35. 6. Carlson RG, Mayfield WR, Normann S, et al. Radiationassociated valvular disease. Chest 1991;99:538–45. 7. Larsen RL, Jakacki RI, Vetter VL, et al. Electrocardiographic changes and arrhythmias after cancer therapy in children and young adults. Am J Cardiol 1992;70:73–7. 8. Adams MJ, Lipsitz SR, Colan SD, et al. Cardiovascular status in long-term survivors of Hodgkin’s disease treated with chest radiotherapy. J Clin Oncol 2004;22:3139–48. 9. Orzan F, Brusca A, Gaita F, et al. Associated cardiac lesions in patients with radiation-induced complete heart block. Int J Cardiol 1993;39:151–6. 10. Slama MS, Le Guludec D, Sebag C, et al. Complete atrioventricular block following mediastinal irradiation: a report of six cases. Pacing Clin Electrophysiol 1991;14: 1112–8.
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Recurrent Syncope Following Radiation Therapy
11. Pohjola-Sintonen S, Totterman KJ, Kupari M. Sick sinus syndrome as a complication of mediastinal radiation therapy. Cancer 1990;65:2494–6. 12. Kaplan BM, Miller AJ, Bharati S, et al. Complete AV block following mediastinal radiation therapy: electrocardiographic and pathologic correlation and review of the world literature. J Interv Card Electrophysiol 1997;1:175–88.
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13. Eriksson P, Hansson PO, Eriksson H, et al. Bundlebranch block in a general male population: the study of men born 1913. Circulation 1998;98:2494–500. 14. Ladero Quesada JM, Amarillas Sanchez L, Furio Bacete V, et al. Peritoneal mesothelioma and complete auriculo-ventricular block as late complications in Hodgkin’s disease. Rev Clin Esp 1991;189:221–3.
June 2006 Volume 331 Number 6
ABSTRACT: This case report describes a 51-year-old man who presented with syncope. His electrocardiogram showed an abnormally long pause and the electrophysiology study revealed a prolonged H-V interval. This was attributed to the radiation therapy he received to the chest. He was successfully treated with implanta-
tion of a permanent pacemaker. This case highlights this rare complication of radiation-induced conduction system disease and management of this potentially lifethreatening condition. KEY INDEXING TERMS: Radiation; Fibrosis; Syncope; Pacemaker. [Am J Med Sci 2006;331(6):325–328.]
C
cantly abnormal for a 1.6-second pause during the first minute of recovery. The baseline electrocardiogram recorded is shown in Figure 1. Cardiac catheterization revealed 50% to 60% stenosis of the proximal and middle left circumflex coronary artery and 30% stenosis of the left anterior descending coronary artery. The right coronary artery showed mild diffuse narrowing. The measured left ventricular ejection fraction was found to be 40%. In view of recurrent syncope and abnormal pause on the exercise electrocardiogram (ECG), the patient underwent an electrophysiology study to look for possible underlying conduction system disease. The intracardiac electrogram (Figure 2) shows an A-H interval of 72 msec and H-V interval of 92 msec, with baseline cycle length of 680 msec. Corrected sinus node recovery time was normal, as was atrial and ventricular stimulation for induction of tachyarrhythmias. We decided to implant a dual-chamber pacemaker in view of the increased H-V interval. The patient has done well since the procedure and has had no recurrence of symptoms.
onduction system disease as a complication of thoracic irradiation is rarely reported in the literature. We present a case of a patient with this condition and discuss the mechanisms and management of radiation-induced fibrosis of the cardiac conduction system. Case Report A 51-year-old obese man presented with recurrent syncope; he had had four episodes over the preceding 3 months. There was no associated palpitations, shortness of breath, or chest pain. His past medical history included type 2 diabetes mellitus, hypertension, asthma, and carcinoid syndrome. He had received three courses of radiation therapy to the chest for the bronchial carcinoid. Review of symptoms was negative for symptoms of recurrence of carcinoid syndrome. Physical examination of the cardiovascular system was unremarkable. Holter monitoring did not show any evidence of tachy- or bradyarrhythmias. Magnetic resonance angiography of the vertebrobasilar vessels demonstrated mild stenosis of the midbasilar artery. Electroencephalography did not show any evidence of seizure-like activity. An exercise stress test was negative for myocardial ischemia but was signifi-
From the Sparrow Health System, Division of Cardiology, Michigan State University, East Lansing, Michiagan. Submitted August 17, 2005; accepted in revised form February 24, 2006. Correspondence: Ranjan K. Thakur, MD, The Thoracic and Cardiovascular Institute, Ingham Regional Medical Center, 405 West Greenlawn Suite 400, Lansing, Michigan 48910 (E-mail: [email protected]). THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Discussion Cardiac damage secondary to thoracic irradiation was first observed the 1930s.1 However, documentation of these events did not occur until the 1960s. This complication of radiation therapy was initially reported in patients receiving thoracic irradiation for Hodgkin’s disease. Irradiation of the chest has been reported to damage all three layers of the heart as well as the conduction system and great vessels. Of these, pericardial disease is the most frequently reported.1–3 325
Recurrent Syncope Following Radiation Therapy
Figure 1. Surface electrocardiogram showing a prolonged PR interval (200 ms) with a left anterior fascicular block (LAFB) and a complete right bundle branch block (RBBB).
Conduction disturbances occur uncommonly by comparison.4 Radiation-induced tissue damage is mediated by free electrons. Although the damage caused by radiation is most toxic to rapidly proliferating cells, slowly dividing cells can also be affected.5 The combination of apoptosis and microvascular destruction leads to ischemic cellular loss and fibrosis.6,7 In our patient, both the mild coronary artery disease and conduction system disease may have been secondary to radiation. The presence of risk factors (obesity, hypertension, type 2 diabetes mellitus) probably contributed to the accelerated atherosclerosis. We believe the most likely cause of heart block was degeneration of the His-Purkinje system secondary to radiation. Radiation therapy primarily affects the anteriormost components of the intracardiac conduction system. In addition, the damage is progressive,8 which is consistent with the ECG findings of right bundle branch block with left anterior fascicular block in our patient. The amount of radiation influences the development of complications. Although the other detrimental effects of radiation therapy have a dose-based relationship (25– 40 Gy), this has not been established for cardiac conduction disturbances.1,4,6 The latent period before the development of various complications ranges from 6 months to 30 years.1,5 Cardiac arrhythmias and conduction disturbances usually occur years after radiation expo326
sure. They should be differentiated from the repolarization abnormalities that are transient and seen shortly after radiation therapy.6 The most serious of the conduction abnormalities include sick sinus syndrome and second- or third-degree heart block.5,7–11,12 Our patient developed heart block after approximately 8 years. His ECG showed first-degree atrioventricular block with a complete right bundle branch block and left anterior fascicular block. A review of literature suggests that infranodal blocks occur more frequently than intrinsic atrioventricular nodal blocks after radiation therapy.5–7,12 The prolonged H-V interval (92 msec) recorded in our patient is also consistent with the infranodal conduction system degeneration (Figure 2). The incidence of bundle branch block increases with aging as a result of increasing fibrosis and calcification of the fibrous skeleton of the heart. In a study carried out by Eriksson et al.13 1% of men aged 50 years developed progressive degenerative disease of the conducting system, as opposed to 17% of subjects at age 80. In view of this, it is unlikely that degeneration fibrosis of the conducting system was the primary cause of heart block in our patient. Implantation of a permanent pacemaker for this condition is beneficial, as observed in most studies.7,10,12,14 Our patient was symptomatic with evidence of diffuse infranodal conduction system disJune 2006 Volume 331 Number 6
Mukerji et al
Figure 2. Intracardiac recording showing normal A-H interval (72 msec) and a prolonged H-V interval of 92 msec (normal, 35–55 msec). The numbers seen along lead II represent heart rate at the respective cycle length (numbers indicated along RVA). HIS, His bundle; HRA, high right atrium; RVA, right ventricular apex.
ease. Hence, we proceeded to implant a permanent pacemaker. Conclusion Fibrosis of the conduction system of the heart is a known but relatively uncommon complication of thoracic irradiation. With the advent of the pacemaker, this potentially fatal condition is amenable to treatment. References 1. Veinot JP, Edwards WD. Pathology of radiation-induced heart disease: a surgical and autopsy study of 27 cases. Hum Pathol 1996;27:766–73. 2. Fajardo LF, Stewart JR, Cohn KE. Morphology of radiation-induced heart disease. Arch Pathol 1968;86:512–9. 3. Schultz-Hector S. Radiation-induced heart disease: review of experimental data on dose response and pathogenesis. Int J Radiat Biol 1992;61:149–60.
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
4. Adams MJ, Lipshultz SE, Schwartz C, et al. Radiation associated cardiovascular disease: manifestations and management. Semin Radiat Oncol 2003;13:346–56. 5. Haimovitz-Friedman A, Kan CC, Ehleiter D, et al. Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis. J Exp Med 1994;180:525–35. 6. Carlson RG, Mayfield WR, Normann S, et al. Radiationassociated valvular disease. Chest 1991;99:538–45. 7. Larsen RL, Jakacki RI, Vetter VL, et al. Electrocardiographic changes and arrhythmias after cancer therapy in children and young adults. Am J Cardiol 1992;70:73–7. 8. Adams MJ, Lipsitz SR, Colan SD, et al. Cardiovascular status in long-term survivors of Hodgkin’s disease treated with chest radiotherapy. J Clin Oncol 2004;22:3139–48. 9. Orzan F, Brusca A, Gaita F, et al. Associated cardiac lesions in patients with radiation-induced complete heart block. Int J Cardiol 1993;39:151–6. 10. Slama MS, Le Guludec D, Sebag C, et al. Complete atrioventricular block following mediastinal irradiation: a report of six cases. Pacing Clin Electrophysiol 1991;14: 1112–8.
327
Recurrent Syncope Following Radiation Therapy
11. Pohjola-Sintonen S, Totterman KJ, Kupari M. Sick sinus syndrome as a complication of mediastinal radiation therapy. Cancer 1990;65:2494–6. 12. Kaplan BM, Miller AJ, Bharati S, et al. Complete AV block following mediastinal radiation therapy: electrocardiographic and pathologic correlation and review of the world literature. J Interv Card Electrophysiol 1997;1:175–88.
328
13. Eriksson P, Hansson PO, Eriksson H, et al. Bundlebranch block in a general male population: the study of men born 1913. Circulation 1998;98:2494–500. 14. Ladero Quesada JM, Amarillas Sanchez L, Furio Bacete V, et al. Peritoneal mesothelioma and complete auriculo-ventricular block as late complications in Hodgkin’s disease. Rev Clin Esp 1991;189:221–3.
June 2006 Volume 331 Number 6