CLINICAL RESEARCH STUDY
Clinical Features and Prognosis of Type 2 Myocardial Infarction in Vasospastic Angina Yuya Matsue, MD,a,b Kazuki Yoshida, MD, MPH,c,d Masahiro Hoshino, MD,a Taishi Yonetsu, MD,a Makoto Suzuki, MD, PhD,a Akihiko Matsumura, MD,a Yuji Hashimoto, MD, PhD,a Masayuki Yoshida, MD, PhDb a Department of Cardiology, Kameda Medical Center, Chiba, Japan; bDepartment of Life Science and Bioethics, Tokyo Medical and Dental University, Tokyo, Japan; cDepartment of Rheumatology, Kameda Medical Center, Chiba, Japan; dDepartment of Epidemiology, Harvard School of Public Health, Boston, Mass.
ABSTRACT BACKGROUND: Although generally the prognosis of vasospastic angina is considered excellent, vasospasm has been shown to be a cause of type 2 myocardial infarction. This study was performed to investigate the clinical characteristics and prognosis of patients with vasospastic angina complicated with type 2 myocardial infarction. METHODS: We performed a retrospective analysis of 171 consecutive patients with definite vasospastic angina (median age, 64 years; 55.0% were male) who visited the Kameda Medical Center with chest pain and in whom cardiac troponin I level was measured between 2005 and 2013. The patients were divided into type 2 myocardial infarction and nonetype 2 myocardial infarction groups. A diagnosis of type 2 myocardial infarction was based on a serum cardiac troponin I value >99th percentile upper reference limit. The primary end point was a combination of nonfatal myocardial infarction or death by any cause. RESULTS: A total of 42 patients (24.6%) were diagnosed with type 2 myocardial infarction, and the type 2 myocardial infarction group had a higher incidence of combined end point than the non-type 2 myocardial infarction group during the median follow-up of 4.4 years (26.2% vs 9.3%, respectively, P ¼ .008). Type 2 myocardial infarction remained an independent predictor of combined end point even after adjusting by the Japanese Coronary Spasm Association risk factors for combined end point (hazard ratio, 2.84; 95% confidence interval, 1.22-6.61; P ¼ .02). CONCLUSIONS: Approximately one quarter of patients with vasospastic angina were associated with type 2 myocardial infarction, and this population should be identified as a new high-risk subgroup of those with vasospastic angina requiring an alternative treatment strategy. Ó 2015 Elsevier Inc. All rights reserved. The American Journal of Medicine (2015) 128, 389-395 KEYWORDS: Prognosis; Troponin; Type 2 myocardial infarction; Vasospasm SEE RELATED EDITORIAL p. 329
Funding: None. Conflict of Interest: KY was funded by a scholarship from Kameda Medical Center at the time of the current research and currently receives tuition support jointly from Japan Student Services Organization and Harvard School of Public Health (partially supported by training grants from Pfizer, Takeda, Bayer, and PhRMA). Authorship: All authors had access to the data and played a role in writing this manuscript. Requests for reprints should be addressed to Yuya Matsue, MD, Department of Cardiology, Kameda Medical Center, 929 Higashi-chou, Kamogawa City, Chiba 296-8602, Japan. E-mail address: [email protected] 0002-9343/$ -see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjmed.2014.10.055
Vasospastic angina is a disease with symptoms of chest pain caused by transient spastic narrowing of an epicardial coronary artery or several epicardial coronary arteries and/or the coronary microvasculature. Although the prognosis is good, some patients have serious cardiac complications, including acute myocardial infarction or sudden cardiac death mainly due to lethal ventricular arrhythmia.1-4 In 2007, the third universal definition of myocardial infarction by the Joint European Society of Cardiology/American College of Cardiology/American Heart Association/World Heart Federation Task Force for the Redefinition of Myocardial
390
The American Journal of Medicine, Vol 128, No 4, April 2015
Infarction classified myocardial infarction into 5 types.5 This incrementally into the left coronary artery (20-100 mg) and classification suggests that coronary vasospasm is one cause of right coronary artery (20-50 mg) over a period of 20 seconds. type 2 myocardial infarction secondary to an ischemic imbalCoronary angiography was performed 1 minute after injection ance. According to this universal definition, patients with of acetylcholine, and vasospastic angina was diagnosed as vasospastic angina with chest pain and cardiac troponin I >99th definite if transient, total, or subtotal occlusion (>90% stepercentile upper reference limit (URL) are diagnosed with type nosis) of a coronary artery with signs or symptoms of 2 myocardial infarction, but this myocardial ischemia (anginal pain population has not been characterand ischemic ST changes) were CLINICAL SIGNIFICANCE ized in detail. We performed a observed.6 retrospective analysis of patients Approximately 25% of cases with vasowith vasospastic angina with and spasm are complicated with type 2 Diagnosis of Type 2 without type 2 myocardial infarction myocardial infarction. The prognosis of to determine the prognostic impliMyocardial Infarction these patients was worse than of pacations and characteristics of vasoCardiac troponin I was measured tients without vasospasm. spastic angina complicated with at least 6 hours after the occurtype 2 myocardial infarction. These patients are a new subgroup of rence of chest pain. In the Kameda Medical Center, troponin I was vasospastic angina with poor prognosis measured using the Stratus CS and require an alternative treatment MATERIALS AND METHODS Troponin I TestPak (Siemens, strategy. Washington, DC) until January Study Design and 2006 and the ST AIA-PACK cTnI Population 3rd-Gen (Tosoh, Tokyo, Japan) A retrospective analysis was performed among all patients from January 2006 to January 2011, after which we used with vasospastic angina who visited the Kameda Medical the Troponin I Ultra (Siemens). Therefore, reference limits Center unexpectedly because of chest pain from January were determined for each assay method to identify whether 2005 to August 2013. We included those patients in whom the troponin I value exceeded the 99th percentile URL of cardiac troponin I was measured at the initial visit. Among each assay used at the Kameda Medical Center. these patients, diagnosis of vasospastic angina was conThe detection limits of these assays and 99th percentile firmed carefully by examination of medical records accordURL were 0.03 ng/mL and 0.07 ng/mL for the Stratus CS ing to the Guidelines for Diagnosis and Treatment of Patients 6 Troponin I, 0.02 ng/mL and 0.04 ng/mL for the ST AIAwith Vasospastic Angina of Japanese Circulation Society, PACK cTnI 3rd-Gen, and 0.006 ng/mL and 0.04 ng/mL and only those patients with a “definite” diagnosis of vasofor the Troponin I Ultra, respectively. spastic angina before the occurrence of chest pain were Coefficients of variation
Clinical Features and Prognosis of Type 2 Myocardial Infarction in Vasospastic Angina Yuya Matsue, MD,a,b Kazuki Yoshida, MD, MPH,c,d Masahiro Hoshino, MD,a Taishi Yonetsu, MD,a Makoto Suzuki, MD, PhD,a Akihiko Matsumura, MD,a Yuji Hashimoto, MD, PhD,a Masayuki Yoshida, MD, PhDb a Department of Cardiology, Kameda Medical Center, Chiba, Japan; bDepartment of Life Science and Bioethics, Tokyo Medical and Dental University, Tokyo, Japan; cDepartment of Rheumatology, Kameda Medical Center, Chiba, Japan; dDepartment of Epidemiology, Harvard School of Public Health, Boston, Mass.
ABSTRACT BACKGROUND: Although generally the prognosis of vasospastic angina is considered excellent, vasospasm has been shown to be a cause of type 2 myocardial infarction. This study was performed to investigate the clinical characteristics and prognosis of patients with vasospastic angina complicated with type 2 myocardial infarction. METHODS: We performed a retrospective analysis of 171 consecutive patients with definite vasospastic angina (median age, 64 years; 55.0% were male) who visited the Kameda Medical Center with chest pain and in whom cardiac troponin I level was measured between 2005 and 2013. The patients were divided into type 2 myocardial infarction and nonetype 2 myocardial infarction groups. A diagnosis of type 2 myocardial infarction was based on a serum cardiac troponin I value >99th percentile upper reference limit. The primary end point was a combination of nonfatal myocardial infarction or death by any cause. RESULTS: A total of 42 patients (24.6%) were diagnosed with type 2 myocardial infarction, and the type 2 myocardial infarction group had a higher incidence of combined end point than the non-type 2 myocardial infarction group during the median follow-up of 4.4 years (26.2% vs 9.3%, respectively, P ¼ .008). Type 2 myocardial infarction remained an independent predictor of combined end point even after adjusting by the Japanese Coronary Spasm Association risk factors for combined end point (hazard ratio, 2.84; 95% confidence interval, 1.22-6.61; P ¼ .02). CONCLUSIONS: Approximately one quarter of patients with vasospastic angina were associated with type 2 myocardial infarction, and this population should be identified as a new high-risk subgroup of those with vasospastic angina requiring an alternative treatment strategy. Ó 2015 Elsevier Inc. All rights reserved. The American Journal of Medicine (2015) 128, 389-395 KEYWORDS: Prognosis; Troponin; Type 2 myocardial infarction; Vasospasm SEE RELATED EDITORIAL p. 329
Funding: None. Conflict of Interest: KY was funded by a scholarship from Kameda Medical Center at the time of the current research and currently receives tuition support jointly from Japan Student Services Organization and Harvard School of Public Health (partially supported by training grants from Pfizer, Takeda, Bayer, and PhRMA). Authorship: All authors had access to the data and played a role in writing this manuscript. Requests for reprints should be addressed to Yuya Matsue, MD, Department of Cardiology, Kameda Medical Center, 929 Higashi-chou, Kamogawa City, Chiba 296-8602, Japan. E-mail address: [email protected] 0002-9343/$ -see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjmed.2014.10.055
Vasospastic angina is a disease with symptoms of chest pain caused by transient spastic narrowing of an epicardial coronary artery or several epicardial coronary arteries and/or the coronary microvasculature. Although the prognosis is good, some patients have serious cardiac complications, including acute myocardial infarction or sudden cardiac death mainly due to lethal ventricular arrhythmia.1-4 In 2007, the third universal definition of myocardial infarction by the Joint European Society of Cardiology/American College of Cardiology/American Heart Association/World Heart Federation Task Force for the Redefinition of Myocardial
390
The American Journal of Medicine, Vol 128, No 4, April 2015
Infarction classified myocardial infarction into 5 types.5 This incrementally into the left coronary artery (20-100 mg) and classification suggests that coronary vasospasm is one cause of right coronary artery (20-50 mg) over a period of 20 seconds. type 2 myocardial infarction secondary to an ischemic imbalCoronary angiography was performed 1 minute after injection ance. According to this universal definition, patients with of acetylcholine, and vasospastic angina was diagnosed as vasospastic angina with chest pain and cardiac troponin I >99th definite if transient, total, or subtotal occlusion (>90% stepercentile upper reference limit (URL) are diagnosed with type nosis) of a coronary artery with signs or symptoms of 2 myocardial infarction, but this myocardial ischemia (anginal pain population has not been characterand ischemic ST changes) were CLINICAL SIGNIFICANCE ized in detail. We performed a observed.6 retrospective analysis of patients Approximately 25% of cases with vasowith vasospastic angina with and spasm are complicated with type 2 Diagnosis of Type 2 without type 2 myocardial infarction myocardial infarction. The prognosis of to determine the prognostic impliMyocardial Infarction these patients was worse than of pacations and characteristics of vasoCardiac troponin I was measured tients without vasospasm. spastic angina complicated with at least 6 hours after the occurtype 2 myocardial infarction. These patients are a new subgroup of rence of chest pain. In the Kameda Medical Center, troponin I was vasospastic angina with poor prognosis measured using the Stratus CS and require an alternative treatment MATERIALS AND METHODS Troponin I TestPak (Siemens, strategy. Washington, DC) until January Study Design and 2006 and the ST AIA-PACK cTnI Population 3rd-Gen (Tosoh, Tokyo, Japan) A retrospective analysis was performed among all patients from January 2006 to January 2011, after which we used with vasospastic angina who visited the Kameda Medical the Troponin I Ultra (Siemens). Therefore, reference limits Center unexpectedly because of chest pain from January were determined for each assay method to identify whether 2005 to August 2013. We included those patients in whom the troponin I value exceeded the 99th percentile URL of cardiac troponin I was measured at the initial visit. Among each assay used at the Kameda Medical Center. these patients, diagnosis of vasospastic angina was conThe detection limits of these assays and 99th percentile firmed carefully by examination of medical records accordURL were 0.03 ng/mL and 0.07 ng/mL for the Stratus CS ing to the Guidelines for Diagnosis and Treatment of Patients 6 Troponin I, 0.02 ng/mL and 0.04 ng/mL for the ST AIAwith Vasospastic Angina of Japanese Circulation Society, PACK cTnI 3rd-Gen, and 0.006 ng/mL and 0.04 ng/mL and only those patients with a “definite” diagnosis of vasofor the Troponin I Ultra, respectively. spastic angina before the occurrence of chest pain were Coefficients of variation
