- Email: [email protected]
Prevalence of Coronary Artery Spasm During Dobutamine Stress Echocardiography
Prevalence of Coronary Artery Spasm During Dobutamine Stress Echocardiography Nicolas Mansencal, MD, PhDa,*, Imane El Hajjaji, MDa,b, Rami El Mahmoud, MDa, Franck Digne, MDa, and Olivier Dubourg, MDa The aim of this study was to assess the prevalence of coronary artery spasm during dobutamine stress echocardiography (DSE). Over a 9-year period (from November 2001 to October 2010) we reviewed all patients (n ⴝ 2,224) referred for DSE. Criteria for selection included patients >18 years old who underwent DSE. We systematically analyzed all electrocardiograms obtained during DSE to detect ST-segment elevation during the examination. All patients with ST-segment elevation underwent coronary angiography. DSE was performed in 2,179 patients. ST-segment elevation was observed in 21 patients, all of whom underwent emergency coronary angiography. In 13 of these 21 patients (62%) significant coronary stenosis was observed: 6 patients with critical coronary stenosis and 7 patients with chronic coronary occlusion. The remaining 8 patients (38% of patients presenting with STsegment elevation during DSE, 7 men, mean age 67 ⴞ 11 years) had no significant coronary stenosis. Prevalence of coronary artery spasm during DSE was 0.4%. In conclusion, physicians should be aware that, although rare, coronary artery spasm may occur during DSE. © 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:800 – 804) Dobutamine stress echocardiography (DSE) is a widely used echocardiographic examination for assessment of coronary ischemia because of its diagnostic and prognostic value.1,2 Several complications or side effects of DSE have been reported such as death, myocardial infarction, supraventricular or ventricular arrhythmias, hypotension, and coronary spasm.3 Vasospasm can be caused by an increase in coronary tone through ␣-adrenergic stimulation.4 However, coronary spasm has been described mainly in case reports and studies remain rare and the prevalence of this specific side effect of DSE is therefore uncertain.5–19 The aim of this study was to assess the prevalence of coronary spasm during DSE. Methods Over a 9-year period (from November 2001 to October 2010) we reviewed all consecutive patients (n ⫽ 2,224) referred for DSE. Entry criteria included an age ⬎18 years and all patients who underwent DSE. We first distinguished patients presenting with normal dobutamine stress echocardiogram (no significant symptoms, electrocardiographic modifications, or wall motion abnormalities during examination) from patients presenting with positive dobutamine stress echocardiographic findings according to guidelines.1,2 In patients presenting a Department of Cardiology, Pôle V Thorax Vasculaire Digestif Métabolisme, Centre de Référence pour les Maladies Cardiaques Héréditaires, Université de Versailles-Saint Quentin, Hôpital Ambroise Paré, Assistance Publique-Hôpitaux de Paris, Boulogne, France; bFaculté de Médecine et de Pharmacie Mohammed V Souissi, Rabat, Morocco. Manuscript received September 4, 2011; revised manuscript received and accepted October 28, 2011. *Corresponding author: Tel: 33-0-149-095-619; fax: 33-0-149-095344. E-mail address: [email protected] (N. Mansencal).
0002-9149/12/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2011.10.044
with positive dobutamine stress echocardiographic findings, we systematically analyzed all electrocardiograms obtained during the echocardiographic examination, thus identifying patients with ST-segment elevation during stress testing. Coronary spasm induced during DSE was defined as a positive dobutamine stress echocardiographic finding with ST-segment elevation and wall motion abnormalities associated with normal coronary angiogram (nonsignificant coronary stenosis). All echocardiographic examinations were performed using a Siemens/Sequoia Acuson C512 system (Acuson, Mountain View, California) equipped with multifrequency transducers and capable of low energy (0.2 to 0.3 mechanical index). For suboptimal acoustic windows, left ventricular cavity opacification was performed by peripheral venous injection of SonoVue contrast agent (Bracco Altana, Inc., Milan, Italy).20 Dobutamine was administered intravenously in an incremental regimen of 10, 20, 30, and 40 g/kg/min every 3 minutes for each dose (from 2001 to 2004) and every 2 minutes after this first period. Atropine (0.25 to 1 mg) was administered at the beginning of dobutamine 20-, 30-, and 40-g/kg/min administration and DSE was stopped when the target heart rate (85% of predicted maximal heart rate [220 minus age {years}]) was achieved. Dobutamine stress echocardiogram was interpreted according to guidelines.1,2,21 All patients with ST-segment elevation during DSE underwent coronary angiography. Significant coronary artery stenosis was defined as ⱖ50% diameter narrowing. Statistical analysis was performed using STATA 8.0 (STATA Corp., College Station, Texas). Continuous variables are presented as mean ⫾ SD and categorical data are presented as absolute value and percentage. Categorical variables were compared using unpaired t tests or Fisher’s exact test as appropriate. www.ajconline.org
⫹ ⫺ ⫺ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫹ ⫹ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫺ ⫹ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ 1 2 3 4 5 6 7 8
†
* Defined as systolic blood pressure ⱖ140 mm Hg and/or diastolic blood pressure ⱖ90 mm Hg. Defined as total cholesterol ⬎2 g/L and/or target level of low-density lipoprotein depending on number of risk factors.
⫺ ⫹ ⫹ ⫹ ⫹ ⫺ ⫹ ⫺ ⫺ ⫺ ⫹ ⫺ ⫹ ⫹ ⫺ ⫺ ⫹ ⫹ ⫹ ⫹ ⫹ ⫺ ⫹ ⫺ ⫺ ⫺ ⫹ ⫺ ⫹ ⫺ ⫺ ⫺ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫺ ⫹ 53/M 57/M 63/M 63/M 66/M 72/M 77/F 86/M
⫹ ⫹ ⫺ ⫹ ⫹ ⫺ ⫹ ⫺
⫹ ⫺ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹
Statins Beta Blockers Anticoagulant
Diabetes Mellitus Smoker
Hypertension*
801
Spontaneous Chest Pain Age (years)/Sex
Of 2,224 patients referred for DSE in our institution, 2,179 (1,649 men, 76%) underwent complete DSE (Figure 1). Mean age was 67 ⫾ 11 years. In the 694 patients presenting with positive dobutamine stress echocardiographic findings, we individualized 21 (1%) with ST-segment elevation during DSE. All these patients underwent emergency coronary angiography. In 13 of these 21 patients (62%), significant coronary stenosis was observed: critical coronary stenosis (i.e., lumen diameter stenosis ⬎80%) was documented in 6 and chronic coronary artery occlusion (i.e., Thrombolysis In Myocardial Infarction grade 0 flow and spontaneously visible collaterals or known coronary occlusion on previous coronary artery angiogram) in 7. In all patients presenting with chronic coronary artery occlusion, Q waves associated with persistent ST-segment elevation were observed at baseline in leads with ST-segment elevation during DSE. Eight patients (Table 1) had no significant coronary stenosis despite ST-segment elevation (38% of patients presenting with ST-segment elevation) always being observed in inferior leads (Figure 2). Prevalence of coronary spasm was 0.4% and no significant difference was observed in patients included before 2005 and patients included later (p ⫽ 0.9). Dobutamine stress echocardiographic characteristics of patients presenting with coronary spasm are presented in Table 2. Only 2 types of dobutamine stress echocardiographic indications were found for these 8 patients: preoperative risk assessment in 3 asymptomatic patients (0.14% of dobutamine stress echocardiograms) and spontaneous episodes of chest pain in 5 patients (0.23% of dobutamine stress echocardiograms). No patient presented with chest pain during exercise. Interestingly, for these 5 patients
Patient Number
Results
Table 1 Characteristics of patients presenting with coronary artery spasm during dobutamine stress echocardiography
Figure 1. Flowchart of patients in study. ECG ⫽ electrocardiographic.
Hypercholestero lemia†
Aortoiliac Occlusive Disease
Antiplatelet Agent
Previous Medical Treatment
Calcium Blockers
Nitrates
Coronary Artery Disease/Dobutamine Stress Echocardiography
802
The American Journal of Cardiology (www.ajconline.org)
Figure 2. Twelve-lead electrocardiogram in a patient presenting with coronary artery spasm during dobutamine stress echocardiography. (A) At baseline no abnormalities were detected. (B) At peak stress the patient presented with chest pain, wall motion abnormalities, and ST-segment elevation in inferior leads associated with ST-segment depression in leads DI, aVL, V1, and V2.
with spontaneous episodes of chest pain, the provoked chest pain during DSE was similar to the chest pain before DSE and was relieved by sublingual nitroglycerin associated with regression of ST-segment elevation. In 2 patients with spontaneous episodes of chest pain, intracoronary methyl ergometrine revealed vasospastic angina. Figure 3 presents the pattern of right coronary artery without medication, with dobutamine infusion, and with intracoronary methyl ergometrine administration in the same patient who presented with spontaneous chest pain. In patients with coronary spasm induced by DSE, mean follow-up was 42 ⫾ 34 months. The 3 asymptomatic patients did not report chest pain during follow-up without medication. In the 5 patients presenting with chest pain at rest, no occurrence of chest pain was observed once calcium blocker treatment was introduced. Discussion In our experience the prevalence of coronary artery spasm during DSE is 0.4%. Interestingly, coronary artery spasm may be considered a side effect of dobutamine or could unmask real vasospastic angina. DSE is a routine test performed for the diagnosis of coronary artery disease because of its accuracy (sensitivity 88% and specificity 83%).1,2 Its indications have increased
notably in recent years, leading to more dobutamine stress echocardiographic tests and consequently more complications. Several complications or side effects of DSE may occur3 and physicians should be aware of this eventuality. The more frequent complications are hypertension and induced arrhythmias.3 However, other less frequent complications may occur such as myocardial infarction, hypotension, and coronary artery spasm.3 Concerning the latter complication, the few data available consist mainly of case reports.5–19 A previous study found that coronary artery spasm on 0.14% of dobutamine stress echocardiograms.15 In the present study we noted ST-segment elevation in 0.96% of dobutamine stress echocardiographic tests. However, presence of ST-segment elevation does not indicate a coronary artery spasm. Indeed, most of these patients presented with significant coronary artery stenosis or chronic occlusion and only 38% of these patients with ST-segment elevation had no significant coronary artery stenosis. Thus, prevalence of coronary artery spasm during DSE was 0.4%, confirming that induced coronary artery spasm remains rare. Interpretation of an occurrence of coronary artery spasm during DSE is difficult. This eventuality is mainly considered a side effect of DSE in addition to hypertension or arrhythmia.3 However, in a previous study 14% of patients with documented vasospastic angina had a positive dobut-
139 129 129 83 80 67 99 70
146 148 133 140 144 132 126 140
109 131 169 143 123 149 152 139
103 131 167 146 109 123 177 144
125 123 157 155 110 140 192 176
90 187 158 141 106 133 175 165
106 235 156 122 106 143 155 142
0 0 0 0 0 0 0 0
1 1 1 1 1 1 1 1
803
70 91 77 58 78 57 81 66 1 2 3 4 5 6 7 8
53 57 63 63 66 72 77 86
62 89 74 62 76 61 66 73
95 94 92 58 79 56 91 73
Peak stress Baseline 30 g/kg/min 20 g/kg/min 40 g/kg/min 30 g/kg/min 20 g/kg/min 10 g/kg/min Baseline
Heart Rate Age (years) Patient Number
Table 2 Characteristics of dobutamine stress echocardiography in patients presenting with coronary artery spasm
Baseline
10 g/kg/min
Systolic Blood Pressure
40 g/kg/min
Significant Wall Motion Abnormalities
Coronary Artery Disease/Dobutamine Stress Echocardiography
Figure 3. Different patterns of right coronary artery spasm during coronary angiography performed in a patient presenting with spontaneous chest pain and ST-segment elevation during dobutamine stress echocardiography (written informed consent provided by patient). (A) Normal right coronary artery at baseline. (B) With dobutamine infusion during coronary angiography (at 40 g/kg/min with progressive increase according to dobutamine stress echocardiographic protocol) a transient occlusion of the right coronary artery was provoked and regressed after injection of intracoronary nitrates. (C) During intracoronary injection of methyl ergometrine, a focal decrease in coronary artery diameter was documented and regressed after injection of intracoronary nitrates.
804
The American Journal of Cardiology (www.ajconline.org)
amine stress echocardiographic test associated with STsegment elevation.11 Interestingly, 3 of our patients with DSE-induced coronary artery spasm were strictly asymptomatic and DSE was performed for preoperative risk assessment. For these patients DSE-induced coronary artery spasm was clearly a side effect of DSE. Conversely, the last 5 patients with ST-segment elevation and no coronary artery stenosis presented with spontaneous chest pain before DSE and DSE induced the same chest pain. Two of these patients had intracoronary methyl ergometrine revealing vasospastic angina; once calcium blocker treatment was initiated, no recurrence of chest pain was seen in either patient. Thus, these patients probably presented with an unknown vasospastic angina and the diagnosis was made thanks to DSE. In 1 patient with coronary spasm induced by DSE (Figure 3) we found that the incremental regimen of dobutamine infusion during coronary angiography was associated with severe coronary spasm of the right coronary artery, which was secondarily reproduced with intracoronary methyl ergometrine. Thus, this case clearly demonstrates that for this patient DSE pointed to a spastic origin of chest pain. The limits of our study are that only 8 patients presented with coronary artery spasm during DSE and that intracoronary methyl ergometrine was not given to all patients with suspected coronary spasm. Coronary artery spasm is a rare complication of DSE with few reported cases, but in our study we systematically analyzed all electrocardiograms obtained during DSE and so were able to clearly diagnose patients with coronary spasm. Concerning the use of intracoronary methyl ergometrine, provocative tests may also induce side effects22 and in our center, once vasospastic angina was suspected (ST-segment elevation without significant coronary artery stenosis), we distinguished asymptomatic patients from patients presenting with spontaneous chest pain. For asymptomatic patients coronary artery spasm during DSE was considered a side effect, whereas symptomatic patients were considered as having vasospastic angina and received calcium blockers, leading to the disappearance of chest pain. 1. Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P, Poldermans D, Voigt JU, Zamorano JL. Stress echocardiography expert consensus statement: European Association of Echocardiography (EAE) (a registered branch of the ESC). Eur J Echocardiogr 2008;9:415– 437. 2. Pellikka PA, Nagueh SF, Elhendy AA, Kuehl CA, Sawada SG; American Society of Echocardiography. American Society of Echocardiography recommendations for performance, interpretation, and application of stress echocardiography. J Am Soc Echocardiogr 2007;20: 1021–1041. 3. Geleijnse ML, Krenning BJ, Nemes A, van Dalen BM, Soliman OI, Ten Cate FJ, Schinkel AF, Boersma E, Simoons ML. Incidence, pathophysiology, and treatment of complications during dobutamineatropine stress echocardiography. Circulation 2010;121:1756 –1767. 4. Dai XZ, Chen DG, Bache RJ. Alpha-adrenergic effects of dopamine and dobutamine on the coronary circulation. J Cardiovasc Pharmacol 1989;14:82– 87. 5. Rekik S, Aboukhoudir F, Andrieu S, Pansieri M, Hirsch JL. Impressive ST-segment elevation during dobutamine stress echocardiography
6.
7.
8. 9.
10.
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14. 15.
16. 17. 18. 19. 20.
21.
22.
in a patient with normal coronary arteries: dobutamine-induced vasospasm? J Electrocardiol 2009;42:414 – 419. Aboukhoudir F, Rekik S, Andrieu S, Cheggour S, Pansieri M, Metge M, Barnay P, Faugier JP, Schouvey S, Quaino G, Unal C, Gonzalez S, Hirsch JL. Coronary artery spasm and dobutamine stress echocardiography. Eur J Echocardiogr 2009;10:556 –561. Bogaz FA, Saroute AN, Tsutsui JM, Kowatsch I, O Neto FM, Nicolau JC, Ramires JA, Mathias Junior W. Coronary spasm induced by dobutamine-atropine stress echocardiography. Arq Bras Cardiol 2006; 87(suppl):e250 – e253. Arruda AL, Barretto RB, Shub C, Chandrasekaran K, Pellikka PA. Prognostic significance of ST-segment elevation during dobutamine stress echocardiography. Am Heart J 2006;151(suppl):744e1–744e6. Ferreira LD, Gil MA, Monaco CG, Silva CE, Peixoto LB, Ortiz J. Coronary artery spasm during dobutamine stress echocardiography in a patient with angiographically normal coronary arteries. Rev Port Cardiol 2004;23:389 –395. Roffi M, Meier B, Allemann Y. Angiographic documented coronary arterial spasm in absence of critical coronary artery stenoses in a patient with variant angina episodes during exercise and dobutamine stress echocardiography. Heart 2000;83(suppl):E4. Kawano H, Fujii H, Motoyama T, Kugiyama K, Ogawa H, Yasue H. Myocardial ischemia due to coronary artery spasm during dobutamine stress echocardiography. Am J Cardiol 2000;85:26 –30. Varga A, Cortigiani L, Rossi PC, Cseh E, De Nes M, Trivieri MG, Csanady M, Picano E. Coronary vasospasm as a source of false positive results during dobutamine echocardiography. Cardiologia 1999;44:907–912. Yamagishi H, Watanabe H, Toda I, Yoshiyama M, Akioka K, Teragaki M, Takeuchi K, Yoshikawa J. A case of dobutamine-induced coronary arterial spasm with ST-segment elevation. Jpn Circ J 1998; 62:150 –151. Previtali M, Fetiveau R, Lanzarini L, Cavalotti C. Dobutamine-induced ST-segment elevation in patients without myocardial infarction. Am J Cardiol 1998;82:1528 –1530. Lamisse N, Cohen A, Chauvel C, Benhalima B, Désert I, Buyukoglu B, Blanchard B, Albo C, Boccara F, Valty J. [Dobutamine stress echocardiography; a monocentric experience on 600 consecutive patients. Effect of age]. Arch Mal Coeur Vaiss 1997;90:1455–1461. Shaheen J, Mendzelevski B, Tzivoni D. Dobutamine-induced ST segment elevation and ventricular fibrillation with nonsignificant coronary artery disease. Am Heart J 1996;132:1058 –1060. Deligonul U, Armbruster R, Hailu A. Provocation of coronary spasm by dobutamine stress echocardiography in a patient with angiographically minimal coronary artery disease. Clin Cardiol 1996;19:755–758. Cohen A, Chauvel C, Benhalima B, Blanchard B. Complication of dobutamine stress echocardiography. Lancet 1995;345:201–202. Previtali M, Lanzarini L, Mussini A, Ferrario M, Angoli L, Specchia G. Dobutamine-induced ST segment elevation in a patient with angina at rest and critical coronary lesions. Eur Heart J 1992;13:997–999. Mansencal N, Nasr IA, Pillière R, Farcot JC, Joseph T, Lacombe P, Dubourg O. Usefulness of contrast echocardiography for assessment of left ventricular thrombus after acute myocardial infarction. Am J Cardiol 2007;99:1667–1670. Douglas PS, Garcia MJ, Haines DE, Lai WW, Manning WJ, Patel AR, Picard MH, Polk DM, Ragosta M, Parker Ward R, Weiner RB. ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 appropriate use criteria for echocardiography. A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Echocardiography, American Heart Association, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Critical Care Medicine, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance American College of Chest Physicians. J Am Soc Echocardiogr 2011;24:229 –267. Hamilton KK, Pepine CJ. A renaissance of provocative testing for coronary spasm? J Am Coll Cardiol 2000;35:1857–1859.
0002-9149/12/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2011.10.044
with positive dobutamine stress echocardiographic findings, we systematically analyzed all electrocardiograms obtained during the echocardiographic examination, thus identifying patients with ST-segment elevation during stress testing. Coronary spasm induced during DSE was defined as a positive dobutamine stress echocardiographic finding with ST-segment elevation and wall motion abnormalities associated with normal coronary angiogram (nonsignificant coronary stenosis). All echocardiographic examinations were performed using a Siemens/Sequoia Acuson C512 system (Acuson, Mountain View, California) equipped with multifrequency transducers and capable of low energy (0.2 to 0.3 mechanical index). For suboptimal acoustic windows, left ventricular cavity opacification was performed by peripheral venous injection of SonoVue contrast agent (Bracco Altana, Inc., Milan, Italy).20 Dobutamine was administered intravenously in an incremental regimen of 10, 20, 30, and 40 g/kg/min every 3 minutes for each dose (from 2001 to 2004) and every 2 minutes after this first period. Atropine (0.25 to 1 mg) was administered at the beginning of dobutamine 20-, 30-, and 40-g/kg/min administration and DSE was stopped when the target heart rate (85% of predicted maximal heart rate [220 minus age {years}]) was achieved. Dobutamine stress echocardiogram was interpreted according to guidelines.1,2,21 All patients with ST-segment elevation during DSE underwent coronary angiography. Significant coronary artery stenosis was defined as ⱖ50% diameter narrowing. Statistical analysis was performed using STATA 8.0 (STATA Corp., College Station, Texas). Continuous variables are presented as mean ⫾ SD and categorical data are presented as absolute value and percentage. Categorical variables were compared using unpaired t tests or Fisher’s exact test as appropriate. www.ajconline.org
⫹ ⫺ ⫺ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫹ ⫹ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫺ ⫹ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ 1 2 3 4 5 6 7 8
†
* Defined as systolic blood pressure ⱖ140 mm Hg and/or diastolic blood pressure ⱖ90 mm Hg. Defined as total cholesterol ⬎2 g/L and/or target level of low-density lipoprotein depending on number of risk factors.
⫺ ⫹ ⫹ ⫹ ⫹ ⫺ ⫹ ⫺ ⫺ ⫺ ⫹ ⫺ ⫹ ⫹ ⫺ ⫺ ⫹ ⫹ ⫹ ⫹ ⫹ ⫺ ⫹ ⫺ ⫺ ⫺ ⫹ ⫺ ⫹ ⫺ ⫺ ⫺ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫺ ⫹ 53/M 57/M 63/M 63/M 66/M 72/M 77/F 86/M
⫹ ⫹ ⫺ ⫹ ⫹ ⫺ ⫹ ⫺
⫹ ⫺ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹
Statins Beta Blockers Anticoagulant
Diabetes Mellitus Smoker
Hypertension*
801
Spontaneous Chest Pain Age (years)/Sex
Of 2,224 patients referred for DSE in our institution, 2,179 (1,649 men, 76%) underwent complete DSE (Figure 1). Mean age was 67 ⫾ 11 years. In the 694 patients presenting with positive dobutamine stress echocardiographic findings, we individualized 21 (1%) with ST-segment elevation during DSE. All these patients underwent emergency coronary angiography. In 13 of these 21 patients (62%), significant coronary stenosis was observed: critical coronary stenosis (i.e., lumen diameter stenosis ⬎80%) was documented in 6 and chronic coronary artery occlusion (i.e., Thrombolysis In Myocardial Infarction grade 0 flow and spontaneously visible collaterals or known coronary occlusion on previous coronary artery angiogram) in 7. In all patients presenting with chronic coronary artery occlusion, Q waves associated with persistent ST-segment elevation were observed at baseline in leads with ST-segment elevation during DSE. Eight patients (Table 1) had no significant coronary stenosis despite ST-segment elevation (38% of patients presenting with ST-segment elevation) always being observed in inferior leads (Figure 2). Prevalence of coronary spasm was 0.4% and no significant difference was observed in patients included before 2005 and patients included later (p ⫽ 0.9). Dobutamine stress echocardiographic characteristics of patients presenting with coronary spasm are presented in Table 2. Only 2 types of dobutamine stress echocardiographic indications were found for these 8 patients: preoperative risk assessment in 3 asymptomatic patients (0.14% of dobutamine stress echocardiograms) and spontaneous episodes of chest pain in 5 patients (0.23% of dobutamine stress echocardiograms). No patient presented with chest pain during exercise. Interestingly, for these 5 patients
Patient Number
Results
Table 1 Characteristics of patients presenting with coronary artery spasm during dobutamine stress echocardiography
Figure 1. Flowchart of patients in study. ECG ⫽ electrocardiographic.
Hypercholestero lemia†
Aortoiliac Occlusive Disease
Antiplatelet Agent
Previous Medical Treatment
Calcium Blockers
Nitrates
Coronary Artery Disease/Dobutamine Stress Echocardiography
802
The American Journal of Cardiology (www.ajconline.org)
Figure 2. Twelve-lead electrocardiogram in a patient presenting with coronary artery spasm during dobutamine stress echocardiography. (A) At baseline no abnormalities were detected. (B) At peak stress the patient presented with chest pain, wall motion abnormalities, and ST-segment elevation in inferior leads associated with ST-segment depression in leads DI, aVL, V1, and V2.
with spontaneous episodes of chest pain, the provoked chest pain during DSE was similar to the chest pain before DSE and was relieved by sublingual nitroglycerin associated with regression of ST-segment elevation. In 2 patients with spontaneous episodes of chest pain, intracoronary methyl ergometrine revealed vasospastic angina. Figure 3 presents the pattern of right coronary artery without medication, with dobutamine infusion, and with intracoronary methyl ergometrine administration in the same patient who presented with spontaneous chest pain. In patients with coronary spasm induced by DSE, mean follow-up was 42 ⫾ 34 months. The 3 asymptomatic patients did not report chest pain during follow-up without medication. In the 5 patients presenting with chest pain at rest, no occurrence of chest pain was observed once calcium blocker treatment was introduced. Discussion In our experience the prevalence of coronary artery spasm during DSE is 0.4%. Interestingly, coronary artery spasm may be considered a side effect of dobutamine or could unmask real vasospastic angina. DSE is a routine test performed for the diagnosis of coronary artery disease because of its accuracy (sensitivity 88% and specificity 83%).1,2 Its indications have increased
notably in recent years, leading to more dobutamine stress echocardiographic tests and consequently more complications. Several complications or side effects of DSE may occur3 and physicians should be aware of this eventuality. The more frequent complications are hypertension and induced arrhythmias.3 However, other less frequent complications may occur such as myocardial infarction, hypotension, and coronary artery spasm.3 Concerning the latter complication, the few data available consist mainly of case reports.5–19 A previous study found that coronary artery spasm on 0.14% of dobutamine stress echocardiograms.15 In the present study we noted ST-segment elevation in 0.96% of dobutamine stress echocardiographic tests. However, presence of ST-segment elevation does not indicate a coronary artery spasm. Indeed, most of these patients presented with significant coronary artery stenosis or chronic occlusion and only 38% of these patients with ST-segment elevation had no significant coronary artery stenosis. Thus, prevalence of coronary artery spasm during DSE was 0.4%, confirming that induced coronary artery spasm remains rare. Interpretation of an occurrence of coronary artery spasm during DSE is difficult. This eventuality is mainly considered a side effect of DSE in addition to hypertension or arrhythmia.3 However, in a previous study 14% of patients with documented vasospastic angina had a positive dobut-
139 129 129 83 80 67 99 70
146 148 133 140 144 132 126 140
109 131 169 143 123 149 152 139
103 131 167 146 109 123 177 144
125 123 157 155 110 140 192 176
90 187 158 141 106 133 175 165
106 235 156 122 106 143 155 142
0 0 0 0 0 0 0 0
1 1 1 1 1 1 1 1
803
70 91 77 58 78 57 81 66 1 2 3 4 5 6 7 8
53 57 63 63 66 72 77 86
62 89 74 62 76 61 66 73
95 94 92 58 79 56 91 73
Peak stress Baseline 30 g/kg/min 20 g/kg/min 40 g/kg/min 30 g/kg/min 20 g/kg/min 10 g/kg/min Baseline
Heart Rate Age (years) Patient Number
Table 2 Characteristics of dobutamine stress echocardiography in patients presenting with coronary artery spasm
Baseline
10 g/kg/min
Systolic Blood Pressure
40 g/kg/min
Significant Wall Motion Abnormalities
Coronary Artery Disease/Dobutamine Stress Echocardiography
Figure 3. Different patterns of right coronary artery spasm during coronary angiography performed in a patient presenting with spontaneous chest pain and ST-segment elevation during dobutamine stress echocardiography (written informed consent provided by patient). (A) Normal right coronary artery at baseline. (B) With dobutamine infusion during coronary angiography (at 40 g/kg/min with progressive increase according to dobutamine stress echocardiographic protocol) a transient occlusion of the right coronary artery was provoked and regressed after injection of intracoronary nitrates. (C) During intracoronary injection of methyl ergometrine, a focal decrease in coronary artery diameter was documented and regressed after injection of intracoronary nitrates.
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The American Journal of Cardiology (www.ajconline.org)
amine stress echocardiographic test associated with STsegment elevation.11 Interestingly, 3 of our patients with DSE-induced coronary artery spasm were strictly asymptomatic and DSE was performed for preoperative risk assessment. For these patients DSE-induced coronary artery spasm was clearly a side effect of DSE. Conversely, the last 5 patients with ST-segment elevation and no coronary artery stenosis presented with spontaneous chest pain before DSE and DSE induced the same chest pain. Two of these patients had intracoronary methyl ergometrine revealing vasospastic angina; once calcium blocker treatment was initiated, no recurrence of chest pain was seen in either patient. Thus, these patients probably presented with an unknown vasospastic angina and the diagnosis was made thanks to DSE. In 1 patient with coronary spasm induced by DSE (Figure 3) we found that the incremental regimen of dobutamine infusion during coronary angiography was associated with severe coronary spasm of the right coronary artery, which was secondarily reproduced with intracoronary methyl ergometrine. Thus, this case clearly demonstrates that for this patient DSE pointed to a spastic origin of chest pain. The limits of our study are that only 8 patients presented with coronary artery spasm during DSE and that intracoronary methyl ergometrine was not given to all patients with suspected coronary spasm. Coronary artery spasm is a rare complication of DSE with few reported cases, but in our study we systematically analyzed all electrocardiograms obtained during DSE and so were able to clearly diagnose patients with coronary spasm. Concerning the use of intracoronary methyl ergometrine, provocative tests may also induce side effects22 and in our center, once vasospastic angina was suspected (ST-segment elevation without significant coronary artery stenosis), we distinguished asymptomatic patients from patients presenting with spontaneous chest pain. For asymptomatic patients coronary artery spasm during DSE was considered a side effect, whereas symptomatic patients were considered as having vasospastic angina and received calcium blockers, leading to the disappearance of chest pain. 1. Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P, Poldermans D, Voigt JU, Zamorano JL. Stress echocardiography expert consensus statement: European Association of Echocardiography (EAE) (a registered branch of the ESC). Eur J Echocardiogr 2008;9:415– 437. 2. Pellikka PA, Nagueh SF, Elhendy AA, Kuehl CA, Sawada SG; American Society of Echocardiography. American Society of Echocardiography recommendations for performance, interpretation, and application of stress echocardiography. J Am Soc Echocardiogr 2007;20: 1021–1041. 3. Geleijnse ML, Krenning BJ, Nemes A, van Dalen BM, Soliman OI, Ten Cate FJ, Schinkel AF, Boersma E, Simoons ML. Incidence, pathophysiology, and treatment of complications during dobutamineatropine stress echocardiography. Circulation 2010;121:1756 –1767. 4. Dai XZ, Chen DG, Bache RJ. Alpha-adrenergic effects of dopamine and dobutamine on the coronary circulation. J Cardiovasc Pharmacol 1989;14:82– 87. 5. Rekik S, Aboukhoudir F, Andrieu S, Pansieri M, Hirsch JL. Impressive ST-segment elevation during dobutamine stress echocardiography
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