Clinical Review & Education
Challenges in Clinical Electrocardiography
A Rare Cause of Chest Pain and Ventricular Fibrillation P. Elliott Miller, MD; Matthew J. Czarny, MD; M. Roselle Abraham, MD
A man in his late 50s presented with sudden-onset chest pain followed by a shock from his implantable cardioverter-defibrillator (ICD). His history included a cardiac arrest secondary to ventricular fibrillation resulting in ICD implantation 1 year prior, chronic obstructive pulmonary disease, hypertension, and active tobacco and alcohol abuse. There was no history of hyperlipidemia or family history of coronary artery disease. His initial symptom was paresthesia in the right hand, which progressed up his arm and was followed by chest tightness and dyspnea. Notably, he had 6 similar presentations in the preceding year, but myocardial infarction had been ruled out by serial electrocardiograms (ECGs) and cardiac biomarker results on all occasions. On arrival to the hospital, his blood pressure was 109/77 mm Hg, heart rate was 66 beats/min, and blood oxygen saturation was 97% while breathing room air. He was admitted to the hospital and received 3 additional shocks from his ICD in the emergency department. Each shock was preceded by chest pain and ECG changes that resolved after administration of sublingual nitroglycerin. One of these ECGs is shown in Figure 1, which prompted immediate coronary angiography. Questions: What is the etiology of his chest pain? Why did his ICD fire?
Patient Course Coronary angiography showed no obstructive coronary artery disease, with only a 30% stenosis in his circumflex coronary artery. Initial views showed diffuse vasospasm of both the right and left coronary arteries, which resolved with administration of intracoronary nitroglycerin (Figure 2). Tests for serum creatine kinase and troponin T had negative results. His lipid panel results were notable for total cholesterol of 127 mg/dL and low-density lipoprotein cholesterol of 67 mg/dL (to convert to millimoles per liter, multiply by 0.0259). Interrogation of the ICD revealed 4 episodes of ventricular fibrillation with appropriate treatment (Figure 3), each preceded by chest pain. He received a diagnosis of coronary vasospasm leading to ventricular fibrillation and was treated with a statin, antiplatelet therapy, long-acting nitrate, and amlodipine besylate (dihydropyridine class of calcium channel blockers). He continued to have recurrent episodes of chest pain and ST-segment elevation while receiving amlodipine, so he was switched to verapamil hydrochloride (phenylalkylamine class of calcium channel blockers), after which he had no recurrence of chest pain or ST-segment elevation on ECG. He was exhorted to cease tobacco and alcohol use and discharged home.
Figure 1. Electrocardiogram Showing ST-Segment Elevations
I
aVR
V1
V4
II
aVL
V2
V5
III
aVF
V3
V6
V1
ST-segment elevations can be seen in the inferior (II, III, and aVF), posterior, and lateral precordial leads with ST-segment depressions in I and aVL.
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JAMA Internal Medicine July 2014 Volume 174, Number 7
Copyright 2014 American Medical Association. All rights reserved.
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Clinical Review & Education Challenges in Clinical Electrocardiography
Figure 2. Coronary Angiography A
B
A, Diffuse coronary artery vasospasm before administration of intracoronary nitroglycerin. B, Relief of vasospasm by intracoronary nitroglycerin therapy.
Figure 3. A Representative Implantable Cardioverter-Defibrillator Interrogation Showing Ventricular Fibrillation (VF) Followed by a Shock and Return to Sinus Rhythm
VT VF VF VF 293 188 143 243 VF VF VF VF VF 155 155 175 150 138
VS VF VF VF 388 155 150 158 VF VF VF 145 138 145
VF 280
VF 158
VS 348
VF 160
VF VF VF 190 193 138 VF VF VF 188 140 138
VT VF VF VF VF VF VF 298 143 268 230 168 150 140 VF VF VF VF VF VF 138 138 168 155 180 148
VS 430
End
The arrowhead shows the transition from VF to sinus rhythm. VS indicates ventricular sensed; VT, ventricular tachycardia.
Discussion Commonly referred to as variant or Prinzmetal angina, coronary artery vasospasm is due to sudden, intense vasoconstriction of an epicardial coronary artery resulting in occlusion or near occlusion of the vessel. It is an infrequent cause of chest pain and is characterized by transient ST-segment elevation. Episodes typically occur at rest and may be more common in the early morning hours. Classically, 1174
coronary angiography shows the absence of flow-limiting stenoses.1 However, it is important to emphasize that vasospasm can occur in patients with coronary artery disease. Therefore, transient STsegment elevations should be treated as spasm along such lesions until proven otherwise. Although not entirely understood, the pathophysiologic mechanism of coronary vasospasm includes endothelial dysfunction and
JAMA Internal Medicine July 2014 Volume 174, Number 7
Copyright 2014 American Medical Association. All rights reserved.
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Challenges in Clinical Electrocardiography Clinical Review & Education
vascular smooth muscle hyperreactivity.1 Cigarette smoking has been associated with coronary artery spasm, with active smokers composing the majority of patients with variant angina in several studies.2 Furthermore, abnormalities in nitric oxide synthase and polymorphisms in its gene have also been associated with vasospasm.1 Patients are typically younger without usual cardiovascular risk factors, with the exception of tobacco use.2,3 Our patient had evidence of diffuse coronary vasospasm on coronary angiography, suggesting the presence of endothelial dysfunction, which may have been induced by cigarette smoking. Furthermore, our patient had several episodes of chest pain and ST-segment elevation despite treatment with nitrates and amlodipine. These symptoms coincided with signs of mild alcohol withdrawal, suggesting the role of sympathetic activation in triggering coronary vasospasm. The diagnosis of variant angina is suggested when a 12-lead ECG or 24-hour Holter monitoring shows transient ST-segment elevation coincident with chest pain and is further corroborated by the absence of flow-limiting stenoses or the presence of coronary artery vasospasm during angiography. In patients with symptoms consistent with vasospasm and without substantial angiographic stenosis, provocation with acetylcholine chloride or ergonovine maleate can be considered, although these maneuvers are almost never performed in contemporary practice.4 A nonpharmacologic maneuver is the hyperventilation test, which has a sensitivity of 62% and specificity of 100%. 5 Notably, patients testing positive by hyperventilation were more likely to have more attacks and severe arrhythmias.5 Our patient had classic, transient ST-segment elevations with onset and resolution perfectly correlating with his chest pain and evidence of diffuse coronary vasospasm on angiography, so no provocative testing was necessary. ARTICLE INFORMATION Author Affiliations: Osler Medical Service, Johns Hopkins School of Medicine, Baltimore, Maryland (Miller); Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, Maryland (Czarny, Abraham). Corresponding Author: P. Elliott Miller, MD, Osler Medical Service, Johns Hopkins School of Medicine, 1830 E Monument St, Room 9029, Baltimore, MD 21205 ([email protected]). Section Editors: Jeffrey Tabas, MD; Paul D. Varosy, MD; Gregory M. Marcus, MD; Nora Goldschlager, MD. Published Online: May 19, 2014. doi:10.1001/jamainternmed.2014.1809. Conflict of Interest Disclosures: None reported. REFERENCES 1. Stern S, Bayes de Luna A. Coronary artery spasm: a 2009 update. Circulation. 2009;119(18):2531-2534. 2. Sugiishi M, Takatsu F. Cigarette smoking is a major risk factor for coronary spasm. Circulation. 1993;87(1):76-79.
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Patients with coronary vasospasm generally do well with medical management and have an excellent 5-year prognosis.6 At least in the short term, it is clear that smoking cessation decreases angina episodes and must be emphasized to patients.7 Calcium channel blockers are generally considered first line and are typically used at the maximum tolerated dose. If symptoms continue, a longacting nitrate or a calcium channel blocker from another class is added.1 The addition of fluvastatin sodium, believed to improve endothelial function, to standard calcium channel blocker therapy lowered the rate of acetylcholine-induced vasospasm on repeated angiography in 1 study.8 Another option for patients resistant to the combination of nitrates and calcium channel blockers is the selective phosphodiesterase-3 inhibitor cilostazol, which was found effective in a small pilot study.9 However, potential proarrhythmic effects precluded use of this agent in our patient. In those with intractable symptoms, coronary artery bypass and percutaneous coronary intervention have been performed.1 Implantation of ICDs has shown promising results in a small cohort of 23 patients with coronary vasospasm and arrhythmias induced by ischemia.10 Although rare, life-threatening ventricular arrhythmias, complete atrioventricular block related to involvement of the right coronary or left circumflex arteries, and myocardial infarction can occur.1
Take-Home Points • Plaque rupture is not the only cause of ST-segment elevation. • The diagnosis of variant or Prinzmetal angina is suggested by nonexertional, acute-onset chest pain with ST-segment elevations. Coronary angiography may show diffuse or focal coronary vasospasm without flow-limiting coronary stenoses. • The mainstay of treatment for coronary vasospasm is calcium channel blockers and long-acting nitrates accompanied by risk factor modification.
3. Nobuyoshi M, Abe M, Nosaka H, et al. Statistical analysis of clinical risk factors for coronary artery spasm: identification of the most important determinant. Am Heart J. 1992;124(1):32-38. 4. Wright RS, Anderson JL, Adams CD, et al; American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American Academy of Family Physicians, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;57(19):e215-e367. 5. Nakao K, Ohgushi M, Yoshimura M, et al. Hyperventilation as a specific test for diagnosis of coronary artery spasm. Am J Cardiol. 1997;80(5): 545-549.
7. Miwa K, Fujita M, Miyagi Y. Beneficial effects of smoking cessation on the short-term prognosis for variant angina—validation of the smoking status by urinary cotinine measurements. Int J Cardiol. 1994;44(2):151-156. 8. Yasue H, Mizuno Y, Harada E, et al; SCAST (Statin and Coronary Artery Spasm Trial) Investigators. Effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin, on coronary spasm after withdrawal of calcium-channel blockers. J Am Coll Cardiol. 2008;51(18):1742-1748. 9. Yoo SY, Song SG, Lee JH, et al. Efficacy of cilostazol on uncontrolled coronary vasospastic angina: a pilot study. Cardiovasc Ther. 2013;31(3): 179-185. 10. Matsue Y, Suzuki M, Nishizaki M, Hojo R, Hashimoto Y, Sakurada H. Clinical implications of an implantable cardioverter-defibrillator in patients with vasospastic angina and lethal ventricular arrhythmia. J Am Coll Cardiol. 2012;60(10):908-913.
6. Yasue H, Takizawa A, Nagao M, et al. Long-term prognosis for patients with variant angina and influential factors. Circulation. 1988;78(1):1-9.
JAMA Internal Medicine July 2014 Volume 174, Number 7
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Nanyang Technological University User on 05/20/2015
1175
Challenges in Clinical Electrocardiography
A Rare Cause of Chest Pain and Ventricular Fibrillation P. Elliott Miller, MD; Matthew J. Czarny, MD; M. Roselle Abraham, MD
A man in his late 50s presented with sudden-onset chest pain followed by a shock from his implantable cardioverter-defibrillator (ICD). His history included a cardiac arrest secondary to ventricular fibrillation resulting in ICD implantation 1 year prior, chronic obstructive pulmonary disease, hypertension, and active tobacco and alcohol abuse. There was no history of hyperlipidemia or family history of coronary artery disease. His initial symptom was paresthesia in the right hand, which progressed up his arm and was followed by chest tightness and dyspnea. Notably, he had 6 similar presentations in the preceding year, but myocardial infarction had been ruled out by serial electrocardiograms (ECGs) and cardiac biomarker results on all occasions. On arrival to the hospital, his blood pressure was 109/77 mm Hg, heart rate was 66 beats/min, and blood oxygen saturation was 97% while breathing room air. He was admitted to the hospital and received 3 additional shocks from his ICD in the emergency department. Each shock was preceded by chest pain and ECG changes that resolved after administration of sublingual nitroglycerin. One of these ECGs is shown in Figure 1, which prompted immediate coronary angiography. Questions: What is the etiology of his chest pain? Why did his ICD fire?
Patient Course Coronary angiography showed no obstructive coronary artery disease, with only a 30% stenosis in his circumflex coronary artery. Initial views showed diffuse vasospasm of both the right and left coronary arteries, which resolved with administration of intracoronary nitroglycerin (Figure 2). Tests for serum creatine kinase and troponin T had negative results. His lipid panel results were notable for total cholesterol of 127 mg/dL and low-density lipoprotein cholesterol of 67 mg/dL (to convert to millimoles per liter, multiply by 0.0259). Interrogation of the ICD revealed 4 episodes of ventricular fibrillation with appropriate treatment (Figure 3), each preceded by chest pain. He received a diagnosis of coronary vasospasm leading to ventricular fibrillation and was treated with a statin, antiplatelet therapy, long-acting nitrate, and amlodipine besylate (dihydropyridine class of calcium channel blockers). He continued to have recurrent episodes of chest pain and ST-segment elevation while receiving amlodipine, so he was switched to verapamil hydrochloride (phenylalkylamine class of calcium channel blockers), after which he had no recurrence of chest pain or ST-segment elevation on ECG. He was exhorted to cease tobacco and alcohol use and discharged home.
Figure 1. Electrocardiogram Showing ST-Segment Elevations
I
aVR
V1
V4
II
aVL
V2
V5
III
aVF
V3
V6
V1
ST-segment elevations can be seen in the inferior (II, III, and aVF), posterior, and lateral precordial leads with ST-segment depressions in I and aVL.
jamainternalmedicine.com
JAMA Internal Medicine July 2014 Volume 174, Number 7
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Nanyang Technological University User on 05/20/2015
1173
Clinical Review & Education Challenges in Clinical Electrocardiography
Figure 2. Coronary Angiography A
B
A, Diffuse coronary artery vasospasm before administration of intracoronary nitroglycerin. B, Relief of vasospasm by intracoronary nitroglycerin therapy.
Figure 3. A Representative Implantable Cardioverter-Defibrillator Interrogation Showing Ventricular Fibrillation (VF) Followed by a Shock and Return to Sinus Rhythm
VT VF VF VF 293 188 143 243 VF VF VF VF VF 155 155 175 150 138
VS VF VF VF 388 155 150 158 VF VF VF 145 138 145
VF 280
VF 158
VS 348
VF 160
VF VF VF 190 193 138 VF VF VF 188 140 138
VT VF VF VF VF VF VF 298 143 268 230 168 150 140 VF VF VF VF VF VF 138 138 168 155 180 148
VS 430
End
The arrowhead shows the transition from VF to sinus rhythm. VS indicates ventricular sensed; VT, ventricular tachycardia.
Discussion Commonly referred to as variant or Prinzmetal angina, coronary artery vasospasm is due to sudden, intense vasoconstriction of an epicardial coronary artery resulting in occlusion or near occlusion of the vessel. It is an infrequent cause of chest pain and is characterized by transient ST-segment elevation. Episodes typically occur at rest and may be more common in the early morning hours. Classically, 1174
coronary angiography shows the absence of flow-limiting stenoses.1 However, it is important to emphasize that vasospasm can occur in patients with coronary artery disease. Therefore, transient STsegment elevations should be treated as spasm along such lesions until proven otherwise. Although not entirely understood, the pathophysiologic mechanism of coronary vasospasm includes endothelial dysfunction and
JAMA Internal Medicine July 2014 Volume 174, Number 7
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Nanyang Technological University User on 05/20/2015
jamainternalmedicine.com
Challenges in Clinical Electrocardiography Clinical Review & Education
vascular smooth muscle hyperreactivity.1 Cigarette smoking has been associated with coronary artery spasm, with active smokers composing the majority of patients with variant angina in several studies.2 Furthermore, abnormalities in nitric oxide synthase and polymorphisms in its gene have also been associated with vasospasm.1 Patients are typically younger without usual cardiovascular risk factors, with the exception of tobacco use.2,3 Our patient had evidence of diffuse coronary vasospasm on coronary angiography, suggesting the presence of endothelial dysfunction, which may have been induced by cigarette smoking. Furthermore, our patient had several episodes of chest pain and ST-segment elevation despite treatment with nitrates and amlodipine. These symptoms coincided with signs of mild alcohol withdrawal, suggesting the role of sympathetic activation in triggering coronary vasospasm. The diagnosis of variant angina is suggested when a 12-lead ECG or 24-hour Holter monitoring shows transient ST-segment elevation coincident with chest pain and is further corroborated by the absence of flow-limiting stenoses or the presence of coronary artery vasospasm during angiography. In patients with symptoms consistent with vasospasm and without substantial angiographic stenosis, provocation with acetylcholine chloride or ergonovine maleate can be considered, although these maneuvers are almost never performed in contemporary practice.4 A nonpharmacologic maneuver is the hyperventilation test, which has a sensitivity of 62% and specificity of 100%. 5 Notably, patients testing positive by hyperventilation were more likely to have more attacks and severe arrhythmias.5 Our patient had classic, transient ST-segment elevations with onset and resolution perfectly correlating with his chest pain and evidence of diffuse coronary vasospasm on angiography, so no provocative testing was necessary. ARTICLE INFORMATION Author Affiliations: Osler Medical Service, Johns Hopkins School of Medicine, Baltimore, Maryland (Miller); Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, Maryland (Czarny, Abraham). Corresponding Author: P. Elliott Miller, MD, Osler Medical Service, Johns Hopkins School of Medicine, 1830 E Monument St, Room 9029, Baltimore, MD 21205 ([email protected]). Section Editors: Jeffrey Tabas, MD; Paul D. Varosy, MD; Gregory M. Marcus, MD; Nora Goldschlager, MD. Published Online: May 19, 2014. doi:10.1001/jamainternmed.2014.1809. Conflict of Interest Disclosures: None reported. REFERENCES 1. Stern S, Bayes de Luna A. Coronary artery spasm: a 2009 update. Circulation. 2009;119(18):2531-2534. 2. Sugiishi M, Takatsu F. Cigarette smoking is a major risk factor for coronary spasm. Circulation. 1993;87(1):76-79.
jamainternalmedicine.com
Patients with coronary vasospasm generally do well with medical management and have an excellent 5-year prognosis.6 At least in the short term, it is clear that smoking cessation decreases angina episodes and must be emphasized to patients.7 Calcium channel blockers are generally considered first line and are typically used at the maximum tolerated dose. If symptoms continue, a longacting nitrate or a calcium channel blocker from another class is added.1 The addition of fluvastatin sodium, believed to improve endothelial function, to standard calcium channel blocker therapy lowered the rate of acetylcholine-induced vasospasm on repeated angiography in 1 study.8 Another option for patients resistant to the combination of nitrates and calcium channel blockers is the selective phosphodiesterase-3 inhibitor cilostazol, which was found effective in a small pilot study.9 However, potential proarrhythmic effects precluded use of this agent in our patient. In those with intractable symptoms, coronary artery bypass and percutaneous coronary intervention have been performed.1 Implantation of ICDs has shown promising results in a small cohort of 23 patients with coronary vasospasm and arrhythmias induced by ischemia.10 Although rare, life-threatening ventricular arrhythmias, complete atrioventricular block related to involvement of the right coronary or left circumflex arteries, and myocardial infarction can occur.1
Take-Home Points • Plaque rupture is not the only cause of ST-segment elevation. • The diagnosis of variant or Prinzmetal angina is suggested by nonexertional, acute-onset chest pain with ST-segment elevations. Coronary angiography may show diffuse or focal coronary vasospasm without flow-limiting coronary stenoses. • The mainstay of treatment for coronary vasospasm is calcium channel blockers and long-acting nitrates accompanied by risk factor modification.
3. Nobuyoshi M, Abe M, Nosaka H, et al. Statistical analysis of clinical risk factors for coronary artery spasm: identification of the most important determinant. Am Heart J. 1992;124(1):32-38. 4. Wright RS, Anderson JL, Adams CD, et al; American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American Academy of Family Physicians, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;57(19):e215-e367. 5. Nakao K, Ohgushi M, Yoshimura M, et al. Hyperventilation as a specific test for diagnosis of coronary artery spasm. Am J Cardiol. 1997;80(5): 545-549.
7. Miwa K, Fujita M, Miyagi Y. Beneficial effects of smoking cessation on the short-term prognosis for variant angina—validation of the smoking status by urinary cotinine measurements. Int J Cardiol. 1994;44(2):151-156. 8. Yasue H, Mizuno Y, Harada E, et al; SCAST (Statin and Coronary Artery Spasm Trial) Investigators. Effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin, on coronary spasm after withdrawal of calcium-channel blockers. J Am Coll Cardiol. 2008;51(18):1742-1748. 9. Yoo SY, Song SG, Lee JH, et al. Efficacy of cilostazol on uncontrolled coronary vasospastic angina: a pilot study. Cardiovasc Ther. 2013;31(3): 179-185. 10. Matsue Y, Suzuki M, Nishizaki M, Hojo R, Hashimoto Y, Sakurada H. Clinical implications of an implantable cardioverter-defibrillator in patients with vasospastic angina and lethal ventricular arrhythmia. J Am Coll Cardiol. 2012;60(10):908-913.
6. Yasue H, Takizawa A, Nagao M, et al. Long-term prognosis for patients with variant angina and influential factors. Circulation. 1988;78(1):1-9.
JAMA Internal Medicine July 2014 Volume 174, Number 7
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a Nanyang Technological University User on 05/20/2015
1175
