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Coronary reactivity testing in vasospastic angina leading to cardiac arrest and coronary dissection
International Journal of Cardiology 210 (2016) 10–13
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Coronary reactivity testing in vasospastic angina leading to cardiac arrest and coronary dissection Massimo Slavich a,⁎, Carlo Ballarotto a, Davide Margonato a, Giovanni Peretto a, Francesco Giannini b, Roberto Spoladore a, Susanna Benincasa b, Michela Cera a, Francesco Maranta a, Federico Pappalardo c, Michele Oppizzi a, Alberto Margonato a a b c
Division of Cardiology, Coronary Care Unit, IRCCS Ospedale San Raffaele, Milan, Italy Interventional Cardiology, IRCCS Ospedale San Raffaele, Milan, Italy Anesthesia and Intensive Care Department, San Raffaele University Hospital, Milan, Italy
a r t i c l e
i n f o
Article history: Received 27 January 2016 Accepted 14 February 2016 Available online 17 February 2016 Keywords: Vasospastic angina Ergonovine test Coronary spasm
1. Case report A 45-year-old woman was admitted to the ER of our hospital because of acute chest pain with ST segment elevation on ECG. She was then referred to the cath lab, where, despite the persistence of symptoms and ECG abnormalities, normal coronary arteries were documented (Fig. 1). Hyperventilation test was negative. On day 2, chest pain without ECG abnormalities was followed by cardiac arrest in VF. On day 6 after admission, coronary angiography with Ergonovine (Erg) test was performed (Fig. 2). After administration of 16 mcg Erg, a severe spasm with total occlusion of the mid-segment of RCA occurred (Fig. 2, panel B). The spasm was resistant to high dosages of intracoronary nitrates, verapamil and nitroprusside. After 1 h of ischemia hemodynamic conditions deteriorated, requiring oro-tracheal intubation. Four episodes of VT–FV immediately treated with DC shock occurred (Fig. 2, panel C). Because of the persistence of hemodynamic instability, and prolonged ischemia exposure, an ExtraCorporeal Membrane Oxygenation System (ECMO) was implanted. In the meantime, the spasm started to evanish with evidence of spiral dissection starting from the middle segment of RCA to the distal
portion of IVP and branch PL, with luminal filling defects, contrast staining in the dissected false lumen and late “slow-flow” (Fig. 2, panel C). After ECMO positioning, three drug eluting stents were implanted with a final TIMI 3 result, with a residual dissection no-flow limiting and absence of staining contrast of the distal segment of PL and IVP (Fig. 2, panel D). Two days later the patient was weaned from ECMO and high dosages of Diltiazem, Nifedipine and nitrates were started. The patient remained asymptomatic for the following days; no asymptomatic ST segment alteration was documented and an ICD was implanted on day 14. She was discharged on day 26 with Diltiazem 120 (3 times/day), Nifedipine 40 mg, and nitrates 20 bid. Her follow-up is negative. 2. Discussion Coronary artery spasm can lead to myocardial infarction, left ventricular dysfunction, promote potentially life threatening arrhythmias and ultimately sudden cardiac death. A key aspect of coronary spasm is its temporarily transient nature which often leads to difficulties in diagnosis [1–5]. A diagnosis of coronary spasm is usually made once coronary spasm is suspected from history and investigations have been performed. These tests may be non-invasive (i.e. hyperventilation) or invasive like coronary reactivity testing (CRT) or may not be needed at all. Indeed, as reported in the Japanese Circulation Society Guidelines, coronary angiography can be avoided altogether if a patient meets all listed criteria for coronary spasm [5]. In our case, coronary artery spasm was the main diagnostic suspect, although during the urgent coronary angiography, despite the presence of symptoms and ECG abnormalities, coronary arteries (baseline and during hyperventilation) were normal. Notably during the following days the patient still complained symptoms without ST segment changes; cardiac arrest occurred after one of these episodes. In our case, 2 key points of interest arise. 2.1. Safety of Ach/Erg test
⁎ Corresponding author at: Division of Cardiology, Coronary Care Unit, Via Olgettina 58, IRCCS Ospedale San Raffaele, Milan, Italy. E-mail address: [email protected] (M. Slavich).
http://dx.doi.org/10.1016/j.ijcard.2016.02.108 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
In usual clinical practice, myocardial spasm provocation tests are not performed routinely because of the concern of adverse events during
Correspondence
11
Fig. 1. Clinical scenario at presentation.
drug administration. We agree that probably the discharge therapy of our patient would have been the same also without Erg testing and ICD in secondary prevention would have been implanted anyway, but the decision to perform CRT and expose the patient to the risk of a provocative test was supported by the safety profile reported by the latest studies, and the need to acquire prognostic information [6–9]. In a retrospective study encompassing more than 20,000 patients that have undergone CRT (10,628 with Ach; 10,884 with Erg), Ach was associated with a higher rate of cardiac complication (0.9% vs 0.4%). However, major cardiac events (defibrillation, chest compression, IABP, ECMO) happened in only 0.7% of patients [6].
In another study on 921 patients with unobstructed coronary arteries, a similar complication rate was observed (only 1% had minor complications and no serious complications occurred [7]). In another study of 1244 patients with variant angina, VT/VF and brady-arrhythmia development was reported in 3.2% (Erg) and 2.7% (Ach) of patients, respectively with an overall incidence of arrhythmic events of 6.8% [8]. Diffuse right coronary artery spasm had a significant correlation with provocation-related VT/VF, while a focal plus diffuse multivessel spasm had an important association with MACEs, whereas provocation-related arrhythmias did not [8]. Another study focused on 293 women with microvascular coronary dysfunction and no obstructive CAD, the risk of serious intra-procedural
12
Correspondence
Fig. 2. Clinical scenario in the cath lab, during Ergonovine test. Yellow arrow: coronary spasm — red circle: coronary dissection.
event was lower (0.7%), when compared to the 2.5% annual major adverse cardiovascular event related to untreated microvascular dysfunction. The authors support the use of CRT for establishing definitive diagnosis and assessing prognosis in this at-risk population [9].
3. Conclusion We hereby report a case of an aggressive form of vasospastic angina. CRT is reported as safe, however potentially life threatening complication might occur. Therefore, a proper trade-off between the advantages and dis-advantages of the related test needs to be considered anytime.
2.2. Spontaneous coronary dissection Coronary artery dissection might occur as a consequence of coronary catheterization, but several series of spontaneous coronary artery dissection (SCAD) have been reported too. Elming and Køber reported a higher prevalence of spontaneous coronary artery dissection in women (73%) than in men, in a series of 142 patients [10]. The pathophysiological mechanism underlying SCAD probably varies between patients [11], but they might all be characterized by an increased in a- and b-adrenergic stimulation, which lead to a calcium ion influx into vascular smooth muscle, and consequent vasoconstriction. The elevated arterial blood pressure in combination with vasoconstriction may induce sharp increases in the shear stress on the arterial wall, leading to an increased risk of dissection even in those with normal coronary arteries [12]. Thus, according to this pathophysiological background, a possible connection between Erg administration, vasoconstriction and SCAD seems reasonable. Isogai et al. were able to retrospectively evaluate all the complications related to CRT in more than 20,000 patients. Notably none experienced SCAD [6]. At the best of our knowledge, only Wei J et al., experience a single coronary dissection in their population of 293 patients that underwent CRT [9].
Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] M. Prinzmetal, R. Kennamer, R. Merliss, et al., Angina pectoris. I. A variant form of angina pectoris; preliminary report, Am. J. Med. 27 (1959) 375. [2] A. Maseri, J.F. Beltrame, H. Shimokawa, Role of coronary vasoconstriction in ischemic heart disease and search for novel therapeutic targets, Circ. J. 73 (2009) 394–403. [3] L.D. Hillis, E. Braunwald, Coronary artery spasm, N. Engl. J. Med. 299 (1978) 695–702. [4] H. Yasue, H. Nakagawa, T. Itoh, E. Harada, Y. Mizuno, Coronary artery spasm — clinical features, diagnosis, pathogenesis, and treatment, J. Cardiol. 51 (2008) 2–17. [5] JCS Joint Working Group, Guidelines for diagnosis and treatment of patients with vasospastic angina (coronary spastic angina) (JCS 2008): digest version, Circ. J. 74 (2010) 1745–1762. [6] T. Isogai, H. Yasunaga, H. Matsui, H. Tanaka, T. Ueda, H. Horiguchi, et al., Serious cardiac complications in coronary spasm provocation tests using acetylcholine or ergonovine: analysis of 21 512 patients from the diagnosis procedure combination database in Japan, Clin. Cardiol. 38 (2015) 171–177. [7] P. Ong, A. Athanasiadis, G. Borgulya, I. Vokshi, R. Bastiaenen, S. Kubik, et al., Clinical usefulness, angiographic characteristics, and safety evaluation of intracoronary acetylcholine provocation testing among 921 consecutive white patients with unobstructed coronary arteries, Circulation 129 (2014) 1723–1730.
Correspondence [8] Y1. Takagi, S. Yasuda, J. Takahashi, R. Tsunoda, Y. Ogata, A. Seki, et al., Clinical implications of provocation tests for coronary artery spasm: safety, arrhythmic complications, and prognostic impact: multicentre registry study of the Japanese Coronary Spasm Association, Eur. Heart J. 34 (4) (Jan 2013) 258–267. [9] J1. Wei, Mehta PK, Johnson BD, B. Samuels, S. Kar, Anderson RD, et al., Safety of coronary reactivity testing in women with no obstructive coronary artery disease: results from the NHLBI-sponsored WISE (Women's Ischemia Syndrome Evaluation) study, JACC Cardiovasc. Interv. 5 (6) (Jun 2012) 646–653.
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[10] H. Elming, L. Køber, Spontaneous coronary artery dissection. case report and literature review, Scand. Cardiovasc. J. 33 (3) (1999) 175–179. [11] W. Tanis, P.R. Stella, J.H. Kirkels, A.H. Pijlman, R.H.J. Peters, F.H. de Man Neth, Spontaneous coronary artery dissection: current insights and therapy, Heart J. 16 (10) (Oct 2008) 344–349. [12] J.R1. Steinhauer, J.B. Caulfield, Spontaneous coronary artery dissection associated with cocaine use: a case report and brief review, Cardiovasc. Pathol. 10 (3) (May-Jun 2001) 141–145.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Coronary reactivity testing in vasospastic angina leading to cardiac arrest and coronary dissection Massimo Slavich a,⁎, Carlo Ballarotto a, Davide Margonato a, Giovanni Peretto a, Francesco Giannini b, Roberto Spoladore a, Susanna Benincasa b, Michela Cera a, Francesco Maranta a, Federico Pappalardo c, Michele Oppizzi a, Alberto Margonato a a b c
Division of Cardiology, Coronary Care Unit, IRCCS Ospedale San Raffaele, Milan, Italy Interventional Cardiology, IRCCS Ospedale San Raffaele, Milan, Italy Anesthesia and Intensive Care Department, San Raffaele University Hospital, Milan, Italy
a r t i c l e
i n f o
Article history: Received 27 January 2016 Accepted 14 February 2016 Available online 17 February 2016 Keywords: Vasospastic angina Ergonovine test Coronary spasm
1. Case report A 45-year-old woman was admitted to the ER of our hospital because of acute chest pain with ST segment elevation on ECG. She was then referred to the cath lab, where, despite the persistence of symptoms and ECG abnormalities, normal coronary arteries were documented (Fig. 1). Hyperventilation test was negative. On day 2, chest pain without ECG abnormalities was followed by cardiac arrest in VF. On day 6 after admission, coronary angiography with Ergonovine (Erg) test was performed (Fig. 2). After administration of 16 mcg Erg, a severe spasm with total occlusion of the mid-segment of RCA occurred (Fig. 2, panel B). The spasm was resistant to high dosages of intracoronary nitrates, verapamil and nitroprusside. After 1 h of ischemia hemodynamic conditions deteriorated, requiring oro-tracheal intubation. Four episodes of VT–FV immediately treated with DC shock occurred (Fig. 2, panel C). Because of the persistence of hemodynamic instability, and prolonged ischemia exposure, an ExtraCorporeal Membrane Oxygenation System (ECMO) was implanted. In the meantime, the spasm started to evanish with evidence of spiral dissection starting from the middle segment of RCA to the distal
portion of IVP and branch PL, with luminal filling defects, contrast staining in the dissected false lumen and late “slow-flow” (Fig. 2, panel C). After ECMO positioning, three drug eluting stents were implanted with a final TIMI 3 result, with a residual dissection no-flow limiting and absence of staining contrast of the distal segment of PL and IVP (Fig. 2, panel D). Two days later the patient was weaned from ECMO and high dosages of Diltiazem, Nifedipine and nitrates were started. The patient remained asymptomatic for the following days; no asymptomatic ST segment alteration was documented and an ICD was implanted on day 14. She was discharged on day 26 with Diltiazem 120 (3 times/day), Nifedipine 40 mg, and nitrates 20 bid. Her follow-up is negative. 2. Discussion Coronary artery spasm can lead to myocardial infarction, left ventricular dysfunction, promote potentially life threatening arrhythmias and ultimately sudden cardiac death. A key aspect of coronary spasm is its temporarily transient nature which often leads to difficulties in diagnosis [1–5]. A diagnosis of coronary spasm is usually made once coronary spasm is suspected from history and investigations have been performed. These tests may be non-invasive (i.e. hyperventilation) or invasive like coronary reactivity testing (CRT) or may not be needed at all. Indeed, as reported in the Japanese Circulation Society Guidelines, coronary angiography can be avoided altogether if a patient meets all listed criteria for coronary spasm [5]. In our case, coronary artery spasm was the main diagnostic suspect, although during the urgent coronary angiography, despite the presence of symptoms and ECG abnormalities, coronary arteries (baseline and during hyperventilation) were normal. Notably during the following days the patient still complained symptoms without ST segment changes; cardiac arrest occurred after one of these episodes. In our case, 2 key points of interest arise. 2.1. Safety of Ach/Erg test
⁎ Corresponding author at: Division of Cardiology, Coronary Care Unit, Via Olgettina 58, IRCCS Ospedale San Raffaele, Milan, Italy. E-mail address: [email protected] (M. Slavich).
http://dx.doi.org/10.1016/j.ijcard.2016.02.108 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
In usual clinical practice, myocardial spasm provocation tests are not performed routinely because of the concern of adverse events during
Correspondence
11
Fig. 1. Clinical scenario at presentation.
drug administration. We agree that probably the discharge therapy of our patient would have been the same also without Erg testing and ICD in secondary prevention would have been implanted anyway, but the decision to perform CRT and expose the patient to the risk of a provocative test was supported by the safety profile reported by the latest studies, and the need to acquire prognostic information [6–9]. In a retrospective study encompassing more than 20,000 patients that have undergone CRT (10,628 with Ach; 10,884 with Erg), Ach was associated with a higher rate of cardiac complication (0.9% vs 0.4%). However, major cardiac events (defibrillation, chest compression, IABP, ECMO) happened in only 0.7% of patients [6].
In another study on 921 patients with unobstructed coronary arteries, a similar complication rate was observed (only 1% had minor complications and no serious complications occurred [7]). In another study of 1244 patients with variant angina, VT/VF and brady-arrhythmia development was reported in 3.2% (Erg) and 2.7% (Ach) of patients, respectively with an overall incidence of arrhythmic events of 6.8% [8]. Diffuse right coronary artery spasm had a significant correlation with provocation-related VT/VF, while a focal plus diffuse multivessel spasm had an important association with MACEs, whereas provocation-related arrhythmias did not [8]. Another study focused on 293 women with microvascular coronary dysfunction and no obstructive CAD, the risk of serious intra-procedural
12
Correspondence
Fig. 2. Clinical scenario in the cath lab, during Ergonovine test. Yellow arrow: coronary spasm — red circle: coronary dissection.
event was lower (0.7%), when compared to the 2.5% annual major adverse cardiovascular event related to untreated microvascular dysfunction. The authors support the use of CRT for establishing definitive diagnosis and assessing prognosis in this at-risk population [9].
3. Conclusion We hereby report a case of an aggressive form of vasospastic angina. CRT is reported as safe, however potentially life threatening complication might occur. Therefore, a proper trade-off between the advantages and dis-advantages of the related test needs to be considered anytime.
2.2. Spontaneous coronary dissection Coronary artery dissection might occur as a consequence of coronary catheterization, but several series of spontaneous coronary artery dissection (SCAD) have been reported too. Elming and Køber reported a higher prevalence of spontaneous coronary artery dissection in women (73%) than in men, in a series of 142 patients [10]. The pathophysiological mechanism underlying SCAD probably varies between patients [11], but they might all be characterized by an increased in a- and b-adrenergic stimulation, which lead to a calcium ion influx into vascular smooth muscle, and consequent vasoconstriction. The elevated arterial blood pressure in combination with vasoconstriction may induce sharp increases in the shear stress on the arterial wall, leading to an increased risk of dissection even in those with normal coronary arteries [12]. Thus, according to this pathophysiological background, a possible connection between Erg administration, vasoconstriction and SCAD seems reasonable. Isogai et al. were able to retrospectively evaluate all the complications related to CRT in more than 20,000 patients. Notably none experienced SCAD [6]. At the best of our knowledge, only Wei J et al., experience a single coronary dissection in their population of 293 patients that underwent CRT [9].
Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] M. Prinzmetal, R. Kennamer, R. Merliss, et al., Angina pectoris. I. A variant form of angina pectoris; preliminary report, Am. J. Med. 27 (1959) 375. [2] A. Maseri, J.F. Beltrame, H. Shimokawa, Role of coronary vasoconstriction in ischemic heart disease and search for novel therapeutic targets, Circ. J. 73 (2009) 394–403. [3] L.D. Hillis, E. Braunwald, Coronary artery spasm, N. Engl. J. Med. 299 (1978) 695–702. [4] H. Yasue, H. Nakagawa, T. Itoh, E. Harada, Y. Mizuno, Coronary artery spasm — clinical features, diagnosis, pathogenesis, and treatment, J. Cardiol. 51 (2008) 2–17. [5] JCS Joint Working Group, Guidelines for diagnosis and treatment of patients with vasospastic angina (coronary spastic angina) (JCS 2008): digest version, Circ. J. 74 (2010) 1745–1762. [6] T. Isogai, H. Yasunaga, H. Matsui, H. Tanaka, T. Ueda, H. Horiguchi, et al., Serious cardiac complications in coronary spasm provocation tests using acetylcholine or ergonovine: analysis of 21 512 patients from the diagnosis procedure combination database in Japan, Clin. Cardiol. 38 (2015) 171–177. [7] P. Ong, A. Athanasiadis, G. Borgulya, I. Vokshi, R. Bastiaenen, S. Kubik, et al., Clinical usefulness, angiographic characteristics, and safety evaluation of intracoronary acetylcholine provocation testing among 921 consecutive white patients with unobstructed coronary arteries, Circulation 129 (2014) 1723–1730.
Correspondence [8] Y1. Takagi, S. Yasuda, J. Takahashi, R. Tsunoda, Y. Ogata, A. Seki, et al., Clinical implications of provocation tests for coronary artery spasm: safety, arrhythmic complications, and prognostic impact: multicentre registry study of the Japanese Coronary Spasm Association, Eur. Heart J. 34 (4) (Jan 2013) 258–267. [9] J1. Wei, Mehta PK, Johnson BD, B. Samuels, S. Kar, Anderson RD, et al., Safety of coronary reactivity testing in women with no obstructive coronary artery disease: results from the NHLBI-sponsored WISE (Women's Ischemia Syndrome Evaluation) study, JACC Cardiovasc. Interv. 5 (6) (Jun 2012) 646–653.
13
[10] H. Elming, L. Køber, Spontaneous coronary artery dissection. case report and literature review, Scand. Cardiovasc. J. 33 (3) (1999) 175–179. [11] W. Tanis, P.R. Stella, J.H. Kirkels, A.H. Pijlman, R.H.J. Peters, F.H. de Man Neth, Spontaneous coronary artery dissection: current insights and therapy, Heart J. 16 (10) (Oct 2008) 344–349. [12] J.R1. Steinhauer, J.B. Caulfield, Spontaneous coronary artery dissection associated with cocaine use: a case report and brief review, Cardiovasc. Pathol. 10 (3) (May-Jun 2001) 141–145.