CLINICAL SPOTLIGHT
Heart, Lung and Circulation (2015) 24, e23–e25 1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2014.09.006
An Unusual Case of Syncope in a Young Female with Incidental Long QTc Interval Joseph Hanna, MRCP a,b, Aiden Lyon, MBBS a, Alice Hawes, MBBS a, Clare Owens, MBBS a, Ravinder Batra, FRACP a,c,1* a
Gold Coast University Hospital, Australia University of Queensland, Australia Griffith University, Australia
b c
Received 14 July 2014; received in revised form 26 August 2014; accepted 14 September 2014; online published-ahead-of-print 28 September 2014
Syncope is a common presentation to emergency departments. Arrhythmias account for 14% of those presentations [1], which requires careful assessment due to the potential for sudden cardiac death (SCD). QTc prolongation either due to congenital channelopathy or acquired aetiology can lead to polymorphic ventricular tachycardia and SCD, and should be excluded on electrocardiography. On the other hand, detailed history and thorough clinical examination are the most important tools in reaching the diagnosis, even in the presence of QTC prolongation. Keywords
Takayasu Syncope Subclavian steal Long QTc Vasculitis
Case report A 23 year-old Caucasian female presented with syncope. She reported brief presyncopal symptoms and palpitations before loss of conscious, awaking on the ground feeling back to normal shortly after. On further questioning, she admitted to feeling generally unwell with lethargy, malaise, loss of appetite and intermittent claudication of the lower limbs over the preceding few weeks. She had a past medical history of seronegative arthritis after having acute onset of symmetrical polyarthralgia two years before. She was started on prednisolone and methotrexate, which was later stopped. There was no family history of cardiovascular disease or sudden cardiac death. On examination, she was a well-looking young lady and noted to have differing blood pressures in her left (80/52 mmHg) and right arm (142/52 mmHg). Blood pressure over both lower limbs was lower than the right upper limb at 86/54 mmHg. A weak left radial pulse could be palpated, compared to a strong right radial, and weaker distal pulses in femoral and dorsalis pedis arteries. On auscultation,
soft systolic murmur was noted with no radiation, but a loud carotid bruit on the left side only with no abnormal bruit on the right side. On posterior chest, normal vesicular breath sounds were present bilaterally, but accompanied by loud interscapular bruit. Her electrocardiogram showed normal sinus rhythm and a prolonged QTc interval at 540 msec. These clinical examination findings were highly suggestive of multiple stenotic lesions of the left subclavian and common carotid arteries as well as the abdominal aorta. Laboratory findings were normocytic anaemia with haemoglobin of 100 g/L and a mean corpuscular volume of 81 fl. The erythrocyte sedimentation rate was raised at 105 mm/h and C-reactive protein at 54 mg/L. An echocardiogram revealed a moderately dilated left ventricle with moderate impairment of LV systolic function, and mild functional mitral regurgitation. Turbulent flow with increased peak velocity of 3.1 m/s was noted on continuous wave Doppler study of abdominal aorta (figure 1). Abdominal computed tomography angiography revealed intimal thickening and stenosis of the descending aorta with beaded appearance. Both renal arteries, superior and inferior
*Corresponding author at: Associate Professor of Medicine, Griffith University and Senior Cardiologist, Gold Coast University Hospital. Tel.: +61756874902; fax: +61756874696, Email: [email protected] 1
Address: Department of Cardiology, Gold Coast University Hospital, 1 Hospital Blvd., Southport, 4215.
© 2014 Published by Elsevier Inc on behalf of Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).
e24
J. Hanna et al.
Figure 1 Continuous flow Doppler assessment of the abdominal aorta showing increased flow velocity to 3.1 m/s.
mesenteric arteries were also affected. This was followed by magnetic resonance imaging and arteriography of the aorta and great vessels that demonstrated complete occlusion of the left subclavian artery and severe narrowing of the left common carotid artery (Figure 2).
Patient was diagnosed with Takayasu arteritis as she fulfilled six of the six diagnostic criteria by the American College of Rheumatology [2]. Despite having a prolonged QTc interval and dilated cardiomyopathy, thorough medical history and clinical examination revealed the true pathophysiology of the patient’s syncope. We believe it was due to subclavian steal phenomenon secondary to severe left subclavian artery stenosis. She was initiated on corticosteroid treatment with prophylactic vitamin D and calcium. She was discharged with planned outpatient assessment for revascularisation.
Discussion
Figure 2 Magnetic resonant arteriography 3D reconstruction showing severe narrowing of the left suclavian and common carotid arteries.
Takayasu arteritis is a large vessel chronic granulomatous vasculitis with a special predilection to the aorta and its great branches. The disease is quite rare with estimated incidence of 2.6 per million, from which 80 to 90% are women [2]. There is a significantly higher incidence in Asian compared to Caucasian population with an estimated incidence of 150 new cases per year in Japan [3]. The pathophysiology of the disease is poorly understood, though a correlation with HLA-Bw52 and HLAB39.2 has been found, suggesting genetic predisposition [4]. The pathogenesis is poorly understood. Histopathological examination of the inflamed artery walls demonstrated intimal hyperplasia and tunica media infiltration with T lymphocytes, B lymphocytes, macrophages and multinucleated giant cells [5,6]. This lead to Interferon g and matrix metalloproteinase mediated matrix damage and eventually, fibrosis and permanent vessel damage. Takayasu disease can affect any part of the cardiovascular system. Inflammation of the aorta and its major branches is
e25
the hallmark of the disease. Subclavian and common carotid arteries are the most common sites [7]. Aortic regurgitation is found in 18% of patients, usually due to aortic root dilatation [8]. Pulmonary artery involvement is demonstrated in half of those patients [9]. Stenotic lesions are the predominant pattern, but aneurysmal dilatation is reported in up to 25% of patients [7]. Coronary arteritis is also not uncommon. In one series of 25 patients, significant coronary artery narrowing of more then 50% was found on invasive coronary angiography [10]. Coronary involvement is usually osteal or proximal. Indeed there are case reports in the literature with dramatic presentations of cardiogenic shock [11], and severe ischaemic cardiomyopathy requiring cardiac transplantation [12]. Systolic left ventricular (LV) dysfunction is not uncommon in Takayasu patients. In one study of 54 patients, 27 had LV ejection fraction less than 45% using radionucleotide ventriculography [13]. Cardiomyopathy can happen due to myocarditis in the absence of valvular regurgitation or coronary vasculitis. Talwar et al, performed endomyocardial biopsies on 16 patients, eight of them had evidence of myocarditis [14]. Syncope is a common presentation of the disease. Subclavian steal refers to reversal of flow in the ipsilateral vertebral artery as a result of subclavian artery occlusion [15]. Although usually asymptomatic, symptoms of cerebral blood flow insufficiency like dizziness, Vertigo, ataxia, diplopia, nystagmus and syncope can occur. These symptoms are collectively termed Subclavian Steal Syndrome. It is well described in Takayasu patients. Yoneda and colleagues used a directional Doppler flowmeter to assess the flow velocity pattern in the vertebral and carotid arteries of five patients. They demonstrated flow reversal in the ipsilateral vertebral artery [16]. Carotid sinus hypersensitivity has also been suggested as a cause of syncope in patients with common carotid artery involvement [17]. In our patient, long QTc masqueraded the diagnosis on presentation. Interestingly, QTc prolongation is common in Takayasu disease independent of coronary arteritis [18]. She also had longstanding facial nerve palsy. Although, trochlear, trigeminal, glossopharyngeal, and hypoglossal involvement has been reported before [19], there are no previous reports of facial nerve involvement prior to this case.
Conclusion Takayasu arteritis is a rare, but important cause of syncope. Diagnosis can be difficult, especially with the presence of prolonged QTc and LV dysfunction, which can be
misleading. Careful history and physical examination are of vital importance in reaching the diagnosis.
References [1] Linzer M, Yang EH, Estes 3rd NA, Wang P, Vorperian VR, Kapoor WN. Diagnosing syncope. Part 1: value of history, physical examination, and electrocardiography. Clinical Efficacy Assessment Project of the American College of Physicians. Ann Intern Med 1997;126(12):989–96. [2] Arend WP, Michel BA, Bloch DA, Hunder GG, Calabrese LH, Edworthy SM, et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum 1990;33(8):1129–34. [3] Koide K. Takayasu arteritis in Japan. Heart Vessels Suppl 1992;7:48–54. [4] Kimura A, Kitamura H, Date Y, Numano F. Comprehensive analysis of HLA genes in Takayasu arteritis in Japan. Int J Cardiol 1996;54(Suppl): S61–9. [5] Hotchi M. Pathological studies on Takayasu arteritis. Heart Vessels Suppl 1992;7:11–7. [6] Inder SJ, Bobryshev YV, Cherian SM, Wang AY, Lord RS, Masuda K, et al. Immunophenotypic analysis of the aortic wall in Takayasu’s arteritis: involvement of lymphocytes, dendritic cells and granulocytes in immuno-inflammatory reactions. Cardiovasc Surg 2000;8(2):141–8. [7] Mwipatayi BP, Jeffery PC, Beningfield SJ, Matley PJ, Naidoo NG, Kalla AA, et al. Takayasu arteritis: clinical features and management: report of 272 cases. ANZ J Surg 2005;75(3):110–7. [8] Lee GY, Jang SY, Ko SM, Kim EK, Lee SH, Han H, et al. Cardiovascular manifestations of Takayasu arteritis and their relationship to the disease activity: analysis of 204 Korean patients at a single center. Int J Cardiol 2012;159(1):14–20. [9] Yamada I, Shibuya H, Matsubara O, Umehara I, Makino T, Numano F, et al. Pulmonary artery disease in Takayasu’s arteritis: angiographic findings. AJR 1992;159(2):263–9. [10] Panja M, Sarkar C, Kar AK, Kumar S, Mazumder B, Roy S, et al. Coronary artery lesions in Takayasu’s arteritis—clinical and angiographic study. J Assoc Physicians India 1998;46(8):678–81. [11] Tacoy G, Akyel A, Tavil Y, Cengel A. Patient with Takayasu arteritis presented as cardiogenic shock. Future Cardiol 2010;6(6):889–93. [12] McBrien A, Griselli M, Friswell M, Hasan A, Kirk R. Heart transplantation following myocardial infarction due to Takayasu’s arteritis. Pediatr Transplant 2012;16(7):E291–5. [13] Talwar KK, Kumar K, Chopra P, Sharma S, Shrivastava S, Wasir HS, et al. Cardiac involvement in nonspecific aortoarteritis (Takayasu’s arteritis). Am Heart J 1991;122(6):1666–70. [14] Talwar KK, Chopra P, Narula J, Shrivastava S, Singh SK, Sharma S, et al. Myocardial involvement and its response to immunosuppressive therapy in nonspecific aortoarteritis (Takayasu’s disease)—a study by endomyocardial biopsy. Int J Cardiol 1988;21(3):323–34. [15] Reivich M, Holling HE, Roberts B, Toole JF. Reversal of blood flow through the vertebral artery and its effect on cerebral circulation. N Engl J Med 1961;265:878–85. [16] Yoneda S, Nukada T, Tada K, Imaizumi M, Takano T. Subclavian steal in Takayasu’s arteritis. A hemodynamic study by means of ultrasonic Doppler flowmetry. Stroke 1977;8(2):264–8. [17] Amiya E, Tanabe K, Ikari Y, Hara K. Carotid sinus hypersensitivity as the initial manifestation of Takayasu arteritis. Intern Med J 2005; 35(11):683–4. [18] Kato T, Kakuta T, Maruyama Y, Hashimoto Y, Yoshimoto N, Numano F. QT dispersion in patients with Takayasu arteritis. Angiology 2000;51 (9):751–6. [19] Wattamwar PR, Doshi SA, Thomas B, Nair M, Kuruvilla A. Hypertrophic pachymeningitis in a patient with Takayasu arteritis: one more association? Ann Indian Acad Neurol 2012;15(1):56–9.
Heart, Lung and Circulation (2015) 24, e23–e25 1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2014.09.006
An Unusual Case of Syncope in a Young Female with Incidental Long QTc Interval Joseph Hanna, MRCP a,b, Aiden Lyon, MBBS a, Alice Hawes, MBBS a, Clare Owens, MBBS a, Ravinder Batra, FRACP a,c,1* a
Gold Coast University Hospital, Australia University of Queensland, Australia Griffith University, Australia
b c
Received 14 July 2014; received in revised form 26 August 2014; accepted 14 September 2014; online published-ahead-of-print 28 September 2014
Syncope is a common presentation to emergency departments. Arrhythmias account for 14% of those presentations [1], which requires careful assessment due to the potential for sudden cardiac death (SCD). QTc prolongation either due to congenital channelopathy or acquired aetiology can lead to polymorphic ventricular tachycardia and SCD, and should be excluded on electrocardiography. On the other hand, detailed history and thorough clinical examination are the most important tools in reaching the diagnosis, even in the presence of QTC prolongation. Keywords
Takayasu Syncope Subclavian steal Long QTc Vasculitis
Case report A 23 year-old Caucasian female presented with syncope. She reported brief presyncopal symptoms and palpitations before loss of conscious, awaking on the ground feeling back to normal shortly after. On further questioning, she admitted to feeling generally unwell with lethargy, malaise, loss of appetite and intermittent claudication of the lower limbs over the preceding few weeks. She had a past medical history of seronegative arthritis after having acute onset of symmetrical polyarthralgia two years before. She was started on prednisolone and methotrexate, which was later stopped. There was no family history of cardiovascular disease or sudden cardiac death. On examination, she was a well-looking young lady and noted to have differing blood pressures in her left (80/52 mmHg) and right arm (142/52 mmHg). Blood pressure over both lower limbs was lower than the right upper limb at 86/54 mmHg. A weak left radial pulse could be palpated, compared to a strong right radial, and weaker distal pulses in femoral and dorsalis pedis arteries. On auscultation,
soft systolic murmur was noted with no radiation, but a loud carotid bruit on the left side only with no abnormal bruit on the right side. On posterior chest, normal vesicular breath sounds were present bilaterally, but accompanied by loud interscapular bruit. Her electrocardiogram showed normal sinus rhythm and a prolonged QTc interval at 540 msec. These clinical examination findings were highly suggestive of multiple stenotic lesions of the left subclavian and common carotid arteries as well as the abdominal aorta. Laboratory findings were normocytic anaemia with haemoglobin of 100 g/L and a mean corpuscular volume of 81 fl. The erythrocyte sedimentation rate was raised at 105 mm/h and C-reactive protein at 54 mg/L. An echocardiogram revealed a moderately dilated left ventricle with moderate impairment of LV systolic function, and mild functional mitral regurgitation. Turbulent flow with increased peak velocity of 3.1 m/s was noted on continuous wave Doppler study of abdominal aorta (figure 1). Abdominal computed tomography angiography revealed intimal thickening and stenosis of the descending aorta with beaded appearance. Both renal arteries, superior and inferior
*Corresponding author at: Associate Professor of Medicine, Griffith University and Senior Cardiologist, Gold Coast University Hospital. Tel.: +61756874902; fax: +61756874696, Email: [email protected] 1
Address: Department of Cardiology, Gold Coast University Hospital, 1 Hospital Blvd., Southport, 4215.
© 2014 Published by Elsevier Inc on behalf of Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).
e24
J. Hanna et al.
Figure 1 Continuous flow Doppler assessment of the abdominal aorta showing increased flow velocity to 3.1 m/s.
mesenteric arteries were also affected. This was followed by magnetic resonance imaging and arteriography of the aorta and great vessels that demonstrated complete occlusion of the left subclavian artery and severe narrowing of the left common carotid artery (Figure 2).
Patient was diagnosed with Takayasu arteritis as she fulfilled six of the six diagnostic criteria by the American College of Rheumatology [2]. Despite having a prolonged QTc interval and dilated cardiomyopathy, thorough medical history and clinical examination revealed the true pathophysiology of the patient’s syncope. We believe it was due to subclavian steal phenomenon secondary to severe left subclavian artery stenosis. She was initiated on corticosteroid treatment with prophylactic vitamin D and calcium. She was discharged with planned outpatient assessment for revascularisation.
Discussion
Figure 2 Magnetic resonant arteriography 3D reconstruction showing severe narrowing of the left suclavian and common carotid arteries.
Takayasu arteritis is a large vessel chronic granulomatous vasculitis with a special predilection to the aorta and its great branches. The disease is quite rare with estimated incidence of 2.6 per million, from which 80 to 90% are women [2]. There is a significantly higher incidence in Asian compared to Caucasian population with an estimated incidence of 150 new cases per year in Japan [3]. The pathophysiology of the disease is poorly understood, though a correlation with HLA-Bw52 and HLAB39.2 has been found, suggesting genetic predisposition [4]. The pathogenesis is poorly understood. Histopathological examination of the inflamed artery walls demonstrated intimal hyperplasia and tunica media infiltration with T lymphocytes, B lymphocytes, macrophages and multinucleated giant cells [5,6]. This lead to Interferon g and matrix metalloproteinase mediated matrix damage and eventually, fibrosis and permanent vessel damage. Takayasu disease can affect any part of the cardiovascular system. Inflammation of the aorta and its major branches is
e25
the hallmark of the disease. Subclavian and common carotid arteries are the most common sites [7]. Aortic regurgitation is found in 18% of patients, usually due to aortic root dilatation [8]. Pulmonary artery involvement is demonstrated in half of those patients [9]. Stenotic lesions are the predominant pattern, but aneurysmal dilatation is reported in up to 25% of patients [7]. Coronary arteritis is also not uncommon. In one series of 25 patients, significant coronary artery narrowing of more then 50% was found on invasive coronary angiography [10]. Coronary involvement is usually osteal or proximal. Indeed there are case reports in the literature with dramatic presentations of cardiogenic shock [11], and severe ischaemic cardiomyopathy requiring cardiac transplantation [12]. Systolic left ventricular (LV) dysfunction is not uncommon in Takayasu patients. In one study of 54 patients, 27 had LV ejection fraction less than 45% using radionucleotide ventriculography [13]. Cardiomyopathy can happen due to myocarditis in the absence of valvular regurgitation or coronary vasculitis. Talwar et al, performed endomyocardial biopsies on 16 patients, eight of them had evidence of myocarditis [14]. Syncope is a common presentation of the disease. Subclavian steal refers to reversal of flow in the ipsilateral vertebral artery as a result of subclavian artery occlusion [15]. Although usually asymptomatic, symptoms of cerebral blood flow insufficiency like dizziness, Vertigo, ataxia, diplopia, nystagmus and syncope can occur. These symptoms are collectively termed Subclavian Steal Syndrome. It is well described in Takayasu patients. Yoneda and colleagues used a directional Doppler flowmeter to assess the flow velocity pattern in the vertebral and carotid arteries of five patients. They demonstrated flow reversal in the ipsilateral vertebral artery [16]. Carotid sinus hypersensitivity has also been suggested as a cause of syncope in patients with common carotid artery involvement [17]. In our patient, long QTc masqueraded the diagnosis on presentation. Interestingly, QTc prolongation is common in Takayasu disease independent of coronary arteritis [18]. She also had longstanding facial nerve palsy. Although, trochlear, trigeminal, glossopharyngeal, and hypoglossal involvement has been reported before [19], there are no previous reports of facial nerve involvement prior to this case.
Conclusion Takayasu arteritis is a rare, but important cause of syncope. Diagnosis can be difficult, especially with the presence of prolonged QTc and LV dysfunction, which can be
misleading. Careful history and physical examination are of vital importance in reaching the diagnosis.
References [1] Linzer M, Yang EH, Estes 3rd NA, Wang P, Vorperian VR, Kapoor WN. Diagnosing syncope. Part 1: value of history, physical examination, and electrocardiography. Clinical Efficacy Assessment Project of the American College of Physicians. Ann Intern Med 1997;126(12):989–96. [2] Arend WP, Michel BA, Bloch DA, Hunder GG, Calabrese LH, Edworthy SM, et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum 1990;33(8):1129–34. [3] Koide K. Takayasu arteritis in Japan. Heart Vessels Suppl 1992;7:48–54. [4] Kimura A, Kitamura H, Date Y, Numano F. Comprehensive analysis of HLA genes in Takayasu arteritis in Japan. Int J Cardiol 1996;54(Suppl): S61–9. [5] Hotchi M. Pathological studies on Takayasu arteritis. Heart Vessels Suppl 1992;7:11–7. [6] Inder SJ, Bobryshev YV, Cherian SM, Wang AY, Lord RS, Masuda K, et al. Immunophenotypic analysis of the aortic wall in Takayasu’s arteritis: involvement of lymphocytes, dendritic cells and granulocytes in immuno-inflammatory reactions. Cardiovasc Surg 2000;8(2):141–8. [7] Mwipatayi BP, Jeffery PC, Beningfield SJ, Matley PJ, Naidoo NG, Kalla AA, et al. Takayasu arteritis: clinical features and management: report of 272 cases. ANZ J Surg 2005;75(3):110–7. [8] Lee GY, Jang SY, Ko SM, Kim EK, Lee SH, Han H, et al. Cardiovascular manifestations of Takayasu arteritis and their relationship to the disease activity: analysis of 204 Korean patients at a single center. Int J Cardiol 2012;159(1):14–20. [9] Yamada I, Shibuya H, Matsubara O, Umehara I, Makino T, Numano F, et al. Pulmonary artery disease in Takayasu’s arteritis: angiographic findings. AJR 1992;159(2):263–9. [10] Panja M, Sarkar C, Kar AK, Kumar S, Mazumder B, Roy S, et al. Coronary artery lesions in Takayasu’s arteritis—clinical and angiographic study. J Assoc Physicians India 1998;46(8):678–81. [11] Tacoy G, Akyel A, Tavil Y, Cengel A. Patient with Takayasu arteritis presented as cardiogenic shock. Future Cardiol 2010;6(6):889–93. [12] McBrien A, Griselli M, Friswell M, Hasan A, Kirk R. Heart transplantation following myocardial infarction due to Takayasu’s arteritis. Pediatr Transplant 2012;16(7):E291–5. [13] Talwar KK, Kumar K, Chopra P, Sharma S, Shrivastava S, Wasir HS, et al. Cardiac involvement in nonspecific aortoarteritis (Takayasu’s arteritis). Am Heart J 1991;122(6):1666–70. [14] Talwar KK, Chopra P, Narula J, Shrivastava S, Singh SK, Sharma S, et al. Myocardial involvement and its response to immunosuppressive therapy in nonspecific aortoarteritis (Takayasu’s disease)—a study by endomyocardial biopsy. Int J Cardiol 1988;21(3):323–34. [15] Reivich M, Holling HE, Roberts B, Toole JF. Reversal of blood flow through the vertebral artery and its effect on cerebral circulation. N Engl J Med 1961;265:878–85. [16] Yoneda S, Nukada T, Tada K, Imaizumi M, Takano T. Subclavian steal in Takayasu’s arteritis. A hemodynamic study by means of ultrasonic Doppler flowmetry. Stroke 1977;8(2):264–8. [17] Amiya E, Tanabe K, Ikari Y, Hara K. Carotid sinus hypersensitivity as the initial manifestation of Takayasu arteritis. Intern Med J 2005; 35(11):683–4. [18] Kato T, Kakuta T, Maruyama Y, Hashimoto Y, Yoshimoto N, Numano F. QT dispersion in patients with Takayasu arteritis. Angiology 2000;51 (9):751–6. [19] Wattamwar PR, Doshi SA, Thomas B, Nair M, Kuruvilla A. Hypertrophic pachymeningitis in a patient with Takayasu arteritis: one more association? Ann Indian Acad Neurol 2012;15(1):56–9.
