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Multivessel Coronary Artery Spasm
CLINICAL SPOTLIGHT
Clinical Spotlight
Multivessel Coronary Artery Spasm J.D. Richardson, MBBS a,b , A.J. Nelson, MBBS a,b , S.G. Worthley, MBBS, PhD a,b , K.S.L. Teo, MBBS, PhD a,b , T. Baillie, MBBS a and M.I. Worthley, MBBS, PhD a,b,∗ a b
Cardiovascular Research Centre, Royal Adelaide Hospital, Australia Department of Medicine, University of Adelaide, Adelaide, Australia
Coronary spasm is increasingly recognised as an important aetiological mechanism causing myocardial ischaemia. Occasionally cases present with evidence of ST segment elevation myocardial infarction, usually secondary to spasm confined to a solitary coronary artery. We present the rare and life-threatening case of severe coronary spasm afflicting all three major epicardial arteries simultaneously. It describes the difficult emergency scenario and ongoing management dilemmas encountered by physicians confronted with multivessel coronary spasm. Moreover we discuss the malignant prognosis associated with this ailment and describe the potential insights provided by cardiac magnetic resonance imaging that might identify those at greatest risk after the index event. (Heart, Lung and Circulation 2012;21:113–116) © 2011 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved. Keywords. Multivessel; Coronary spasm; Magnetic resonance imaging
Introduction
P
rinzmetal first delivered his seminal report [1] describing a variant form of angina in 1959. His observations documented the unusual but distinctive findings of angina at rest, associated with dramatic transient ECG changes and, in the rare minority reaching post mortem, an absence of a significant coronary stenosis. Up to 30% of patients with acute coronary syndrome (ACS) undergoing angiography have non obstructive disease [2]. Invasive acetylcholine provocation suggest as many as 50% of these may have coronary spasm. The pathophysiology behind coronary spasm is incompletely characterised. Perturbations of the mechanisms that ordinarily maintain coronary arterial tone have been implicated. In particular a reduction in endogenous nitric oxide bioavailability is thought to play a critical role [3]. Certain genetic and environmental factors that affect this bioavailability, such as smoking [4], are strongly linked to coronary artery spasm. Furthermore significant racial differences in coronary reactivity exist, with Asian patients exhibiting a threefold higher incidence of coronary spasm compared to Caucasian patients [5]. Medical therapy with calcium channel blockers and nitrates are the mainstay of treatment for coronary artery spasm. The use of -blockers is traditionally
Received 11 March 2011; accepted 22 July 2011; available online 17 August 2011 ∗
Corresponding author at: Cardiovascular Investigation Unit, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia. Tel.: +61 8 8222 5608; fax: +61 8 8222 2454. E-mail address: [email protected] (M.I. Worthley).
avoided given their potential detrimental effect of limiting -receptor mediated dilatation and promotion of unopposed alpha adrenergic coronary vasoconstriction. The degree of vasoconstriction during spasm ranges from the clinically undetectable to complete occlusion. In severe or prolonged cases of ischaemia, myocardial infarction may ensue. Whilst few multivessel spasm cases have been reported previously [6,7], this case highlights that poor outcome of such cases and proposes that early cardiac magnetic resonance (CMR) imaging may ultimately guide the physician to early implantable defibrillator therapy.
Case A 31 year-old Chinese woman presented with intermittent lower retrosternal chest pain. The only past medical history was mild asthma. She was a smoker with no relevant family history. She denied illicit drug use and her drug screen was negative. Over the preceding two months she had presented to emergency departments on three occasions with chest pain. This was described as burning in nature radiating through to the back, with each event occurring early morning. There was no exertional component. She was commenced on a proton pump inhibitor for treatment of presumed gastroesophageal reflux disease, and discharged home without further investigations. Her electrocardiogram on each occasion was reported as normal. Shortly after, her symptoms had deteriorated with increased frequency, severity and duration of pain. She then presented to the Emergency Department at our institution. Clinical examination was unremarkable, however the electrocardiogram showed inferolateral T wave inversion (Fig. 1a). Troponin T level was elevated (0.24 g/L)
© 2011 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.
1443-9506/04/$36.00 doi:10.1016/j.hlc.2011.07.007
114
Richardson et al. Multivessel Coronary Artery Spasm
Heart, Lung and Circulation 2012;21:113–116
CLINICAL SPOTLIGHT
Figure 1. (a) Presenting electrocardiograph showing inferolateral T wave inversion and (b) ST elevation in the anterior leads.
and treatment was commenced for a presumed ACS. Two hours later the pain recurred, but more severely. The electrocardiogram exhibited evidence of evolving ST segment elevation in the anterior leads (Fig. 1b). During transfer for emergent coronary angiography she suffered a cardiac arrest. Ventricular fibrillation was promptly treated with one 200J DC cardioversion. Coronary angiography showed an occluded proximal right coronary artery and proximal left anterior descending artery with an occlusion in the mid vessel of the circumflex artery (Fig. 2a, b). Notwithstanding the low blood pressure (SBP 40 mmHg) intracoronary glyceryl trinitrate was administered with immediate improved vessel patency and blood pressure with no evidence of atherosclerosis or thrombus seen (Fig. 2c, d). An intravenous glyceryl trinitrate infusion was commenced and her condition stabilised. Transthoracic echocardiography showed moderately impaired left ventricular function (EF 40%). She was discharged home at day 10, free of symptoms, on maximally tolerated doses of a calcium channel blocker and isosorbide mononitrate. The extent and transmurality of myocardial scar after infarction as detected by late enhancement CMR is a stronger predictor of events than LV ejection fraction [8]. CMR was undertaken as an outpatient three weeks post
MI and demonstrated severe left ventricular impairment (EF 34%) with akinetic septum, anteroseptum and anterior wall. Late gadolinium enhancement studies (Fig. 3) showed transmural infarction in the LAD distribution, demonstrating non-viable myocardium. The inferior wall was hypokinetic with approximately 50% mural infarction suggesting intermediate viability. The lateral wall exhibited normal systolic contraction with evidence of <25% thickness infarction. These findings are consistent with the ECG showing Q waves and loss of R wave anteriorly with normal QRS duration. She was reviewed within four weeks of discharge from hospital, with a plan for insertion of an implantable defibrillator. She was clinically stable except for a persistently low blood pressure (80/50 mmHg), which precluded the initiation of an angiotensin converting enzyme inhibitor. Furthermore a  blocker was not initiated due to concerns regarding both further lowering of blood pressure as well as potentially exacerbating her coronary spasm. She tragically died one week after her physician appointment secondary to presumed ventricular arrhythmia.
Discussion The clinical importance of coronary spasm is now increasingly recognised since its description 52 years ago. It has a
Richardson et al. Multivessel Coronary Artery Spasm
115 CLINICAL SPOTLIGHT
Heart, Lung and Circulation 2012;21:113–116
Figure 2. Presenting angiographic pictures of (a) right coronary artery and (b) left coronary system. Angiographic pictures following intracoronary administration of glyceryl trinitrate of the (c) right coronary artery and (d) left coronary system.
broad spectrum of presentation and in its mildest form has an excellent prognosis. However in more severe malignant cases prognosis is guarded. Spasm leading to simultaneous occlusion of all three major epicardial arteries is both very rare and life threatening. Prompt identification of the underlying aetiology and initiation of appropriate vasodilator therapy can rescue such cases. Optimal
medical therapy thereafter can be difficult to attain considering the symptomatic hypotension caused by vasodilator therapy. This coupled with the need to prioritise “spasm therapy” over often conflicting “left ventricular dysfunction” treatment (e.g.  blockers) also provides a clinical dilemma. CMR imaging allows unsurpassed evaluation of left ventricular systolic function and assessment of
Figure 3. Cardiac magnetic resonance images showing anteroseptal myocardial infarction, in the (a) horizontal long axis, (b) vertical long axis and (c) short axis view of the left ventricle.
116
Richardson et al. Multivessel Coronary Artery Spasm
CLINICAL SPOTLIGHT
myocardial scar and viability. In such malignant cases, with severely impaired left ventricular systolic function with associated full thickness scarred myocardium, device therapy may need to be incorporated earlier than current guidelines permit post myocardial infarction. This case outlines the rare but life threatening consequence of severe spasm afflicting multiple coronary arteries and the poor prognosis in survivors of the index event.
Heart, Lung and Circulation 2012;21:113–116
[4] [5]
[6]
References [1] Prinzmetal M, Kennamer R, Merliss R, Wada T, Bor N. Angina pectoris. I. A variant form of angina pectoris; preliminary report. Am J Med 1959;27(September):375–88. [2] Ong P, Athanasiadis A, Hill S, Vogelsberg H, Voehringer M, Sechtem U. Coronary artery spasm as a frequent cause of acute coronary syndrome: The CASPAR Study. J Am Coll Cardiol 2008;52(August (7)):523–7. [3] Egashira K, Katsuda Y, Mohri M, Kuga T, Tagawa T, Shimokawa H, et al. Basal release of endothelium-derived
[7]
[8]
nitric oxide at site of spasm in patients with variant angina. J Am Coll Cardiol 1996;27(May (6)):1444–9. Sugiishi M, Takatsu F. Cigarette smoking is a major risk factor for coronary spasm. Circulation 1993;87(January (1)):76–9. Pristipino C, Beltrame JF, Finocchiaro ML, Hattori R, Fujita M, Mongiardo R, et al. Major racial differences in coronary constrictor response between Japanese and Caucasians with recent myocardial infarction. Circulation 2000;101(March (10)):1102–8. Chuang YT, Ueng KC. Spontaneous and simultaneous multivessel coronary spasm causing multisite myocardial infarction, cardiogenic shock, atrioventricular block, and ventricular fibrillation. Circ J 2009;73(October (10)):1961–4. Haghi D, Suselbeck T, Wolpert C. Severe multivessel coronary vasospasm and left ventricular ballooning syndrome. Circ Cardiovasc Interv 2009;2(June (3)):268–9. Roes SD, Kelle S, Kaandorp TA, Kokocinski T, Poldermans D, Lamb HJ, et al. Comparison of myocardial infarct size assessed with contrast-enhanced magnetic resonance imaging and left ventricular function and volumes to predict mortality in patients with healed myocardial infarction. Am J Cardiol 2007;100(September (6)):930–6.
Clinical Spotlight
Multivessel Coronary Artery Spasm J.D. Richardson, MBBS a,b , A.J. Nelson, MBBS a,b , S.G. Worthley, MBBS, PhD a,b , K.S.L. Teo, MBBS, PhD a,b , T. Baillie, MBBS a and M.I. Worthley, MBBS, PhD a,b,∗ a b
Cardiovascular Research Centre, Royal Adelaide Hospital, Australia Department of Medicine, University of Adelaide, Adelaide, Australia
Coronary spasm is increasingly recognised as an important aetiological mechanism causing myocardial ischaemia. Occasionally cases present with evidence of ST segment elevation myocardial infarction, usually secondary to spasm confined to a solitary coronary artery. We present the rare and life-threatening case of severe coronary spasm afflicting all three major epicardial arteries simultaneously. It describes the difficult emergency scenario and ongoing management dilemmas encountered by physicians confronted with multivessel coronary spasm. Moreover we discuss the malignant prognosis associated with this ailment and describe the potential insights provided by cardiac magnetic resonance imaging that might identify those at greatest risk after the index event. (Heart, Lung and Circulation 2012;21:113–116) © 2011 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved. Keywords. Multivessel; Coronary spasm; Magnetic resonance imaging
Introduction
P
rinzmetal first delivered his seminal report [1] describing a variant form of angina in 1959. His observations documented the unusual but distinctive findings of angina at rest, associated with dramatic transient ECG changes and, in the rare minority reaching post mortem, an absence of a significant coronary stenosis. Up to 30% of patients with acute coronary syndrome (ACS) undergoing angiography have non obstructive disease [2]. Invasive acetylcholine provocation suggest as many as 50% of these may have coronary spasm. The pathophysiology behind coronary spasm is incompletely characterised. Perturbations of the mechanisms that ordinarily maintain coronary arterial tone have been implicated. In particular a reduction in endogenous nitric oxide bioavailability is thought to play a critical role [3]. Certain genetic and environmental factors that affect this bioavailability, such as smoking [4], are strongly linked to coronary artery spasm. Furthermore significant racial differences in coronary reactivity exist, with Asian patients exhibiting a threefold higher incidence of coronary spasm compared to Caucasian patients [5]. Medical therapy with calcium channel blockers and nitrates are the mainstay of treatment for coronary artery spasm. The use of -blockers is traditionally
Received 11 March 2011; accepted 22 July 2011; available online 17 August 2011 ∗
Corresponding author at: Cardiovascular Investigation Unit, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia. Tel.: +61 8 8222 5608; fax: +61 8 8222 2454. E-mail address: [email protected] (M.I. Worthley).
avoided given their potential detrimental effect of limiting -receptor mediated dilatation and promotion of unopposed alpha adrenergic coronary vasoconstriction. The degree of vasoconstriction during spasm ranges from the clinically undetectable to complete occlusion. In severe or prolonged cases of ischaemia, myocardial infarction may ensue. Whilst few multivessel spasm cases have been reported previously [6,7], this case highlights that poor outcome of such cases and proposes that early cardiac magnetic resonance (CMR) imaging may ultimately guide the physician to early implantable defibrillator therapy.
Case A 31 year-old Chinese woman presented with intermittent lower retrosternal chest pain. The only past medical history was mild asthma. She was a smoker with no relevant family history. She denied illicit drug use and her drug screen was negative. Over the preceding two months she had presented to emergency departments on three occasions with chest pain. This was described as burning in nature radiating through to the back, with each event occurring early morning. There was no exertional component. She was commenced on a proton pump inhibitor for treatment of presumed gastroesophageal reflux disease, and discharged home without further investigations. Her electrocardiogram on each occasion was reported as normal. Shortly after, her symptoms had deteriorated with increased frequency, severity and duration of pain. She then presented to the Emergency Department at our institution. Clinical examination was unremarkable, however the electrocardiogram showed inferolateral T wave inversion (Fig. 1a). Troponin T level was elevated (0.24 g/L)
© 2011 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.
1443-9506/04/$36.00 doi:10.1016/j.hlc.2011.07.007
114
Richardson et al. Multivessel Coronary Artery Spasm
Heart, Lung and Circulation 2012;21:113–116
CLINICAL SPOTLIGHT
Figure 1. (a) Presenting electrocardiograph showing inferolateral T wave inversion and (b) ST elevation in the anterior leads.
and treatment was commenced for a presumed ACS. Two hours later the pain recurred, but more severely. The electrocardiogram exhibited evidence of evolving ST segment elevation in the anterior leads (Fig. 1b). During transfer for emergent coronary angiography she suffered a cardiac arrest. Ventricular fibrillation was promptly treated with one 200J DC cardioversion. Coronary angiography showed an occluded proximal right coronary artery and proximal left anterior descending artery with an occlusion in the mid vessel of the circumflex artery (Fig. 2a, b). Notwithstanding the low blood pressure (SBP 40 mmHg) intracoronary glyceryl trinitrate was administered with immediate improved vessel patency and blood pressure with no evidence of atherosclerosis or thrombus seen (Fig. 2c, d). An intravenous glyceryl trinitrate infusion was commenced and her condition stabilised. Transthoracic echocardiography showed moderately impaired left ventricular function (EF 40%). She was discharged home at day 10, free of symptoms, on maximally tolerated doses of a calcium channel blocker and isosorbide mononitrate. The extent and transmurality of myocardial scar after infarction as detected by late enhancement CMR is a stronger predictor of events than LV ejection fraction [8]. CMR was undertaken as an outpatient three weeks post
MI and demonstrated severe left ventricular impairment (EF 34%) with akinetic septum, anteroseptum and anterior wall. Late gadolinium enhancement studies (Fig. 3) showed transmural infarction in the LAD distribution, demonstrating non-viable myocardium. The inferior wall was hypokinetic with approximately 50% mural infarction suggesting intermediate viability. The lateral wall exhibited normal systolic contraction with evidence of <25% thickness infarction. These findings are consistent with the ECG showing Q waves and loss of R wave anteriorly with normal QRS duration. She was reviewed within four weeks of discharge from hospital, with a plan for insertion of an implantable defibrillator. She was clinically stable except for a persistently low blood pressure (80/50 mmHg), which precluded the initiation of an angiotensin converting enzyme inhibitor. Furthermore a  blocker was not initiated due to concerns regarding both further lowering of blood pressure as well as potentially exacerbating her coronary spasm. She tragically died one week after her physician appointment secondary to presumed ventricular arrhythmia.
Discussion The clinical importance of coronary spasm is now increasingly recognised since its description 52 years ago. It has a
Richardson et al. Multivessel Coronary Artery Spasm
115 CLINICAL SPOTLIGHT
Heart, Lung and Circulation 2012;21:113–116
Figure 2. Presenting angiographic pictures of (a) right coronary artery and (b) left coronary system. Angiographic pictures following intracoronary administration of glyceryl trinitrate of the (c) right coronary artery and (d) left coronary system.
broad spectrum of presentation and in its mildest form has an excellent prognosis. However in more severe malignant cases prognosis is guarded. Spasm leading to simultaneous occlusion of all three major epicardial arteries is both very rare and life threatening. Prompt identification of the underlying aetiology and initiation of appropriate vasodilator therapy can rescue such cases. Optimal
medical therapy thereafter can be difficult to attain considering the symptomatic hypotension caused by vasodilator therapy. This coupled with the need to prioritise “spasm therapy” over often conflicting “left ventricular dysfunction” treatment (e.g.  blockers) also provides a clinical dilemma. CMR imaging allows unsurpassed evaluation of left ventricular systolic function and assessment of
Figure 3. Cardiac magnetic resonance images showing anteroseptal myocardial infarction, in the (a) horizontal long axis, (b) vertical long axis and (c) short axis view of the left ventricle.
116
Richardson et al. Multivessel Coronary Artery Spasm
CLINICAL SPOTLIGHT
myocardial scar and viability. In such malignant cases, with severely impaired left ventricular systolic function with associated full thickness scarred myocardium, device therapy may need to be incorporated earlier than current guidelines permit post myocardial infarction. This case outlines the rare but life threatening consequence of severe spasm afflicting multiple coronary arteries and the poor prognosis in survivors of the index event.
Heart, Lung and Circulation 2012;21:113–116
[4] [5]
[6]
References [1] Prinzmetal M, Kennamer R, Merliss R, Wada T, Bor N. Angina pectoris. I. A variant form of angina pectoris; preliminary report. Am J Med 1959;27(September):375–88. [2] Ong P, Athanasiadis A, Hill S, Vogelsberg H, Voehringer M, Sechtem U. Coronary artery spasm as a frequent cause of acute coronary syndrome: The CASPAR Study. J Am Coll Cardiol 2008;52(August (7)):523–7. [3] Egashira K, Katsuda Y, Mohri M, Kuga T, Tagawa T, Shimokawa H, et al. Basal release of endothelium-derived
[7]
[8]
nitric oxide at site of spasm in patients with variant angina. J Am Coll Cardiol 1996;27(May (6)):1444–9. Sugiishi M, Takatsu F. Cigarette smoking is a major risk factor for coronary spasm. Circulation 1993;87(January (1)):76–9. Pristipino C, Beltrame JF, Finocchiaro ML, Hattori R, Fujita M, Mongiardo R, et al. Major racial differences in coronary constrictor response between Japanese and Caucasians with recent myocardial infarction. Circulation 2000;101(March (10)):1102–8. Chuang YT, Ueng KC. Spontaneous and simultaneous multivessel coronary spasm causing multisite myocardial infarction, cardiogenic shock, atrioventricular block, and ventricular fibrillation. Circ J 2009;73(October (10)):1961–4. Haghi D, Suselbeck T, Wolpert C. Severe multivessel coronary vasospasm and left ventricular ballooning syndrome. Circ Cardiovasc Interv 2009;2(June (3)):268–9. Roes SD, Kelle S, Kaandorp TA, Kokocinski T, Poldermans D, Lamb HJ, et al. Comparison of myocardial infarct size assessed with contrast-enhanced magnetic resonance imaging and left ventricular function and volumes to predict mortality in patients with healed myocardial infarction. Am J Cardiol 2007;100(September (6)):930–6.