今日の臨床サポート

冠攣縮性狭心症

著者: 海北幸一1) 熊本大学大学院 生命科学研究部 循環器内科学

著者: 小川久雄2) 国立循環器病研究センター

監修: 伊藤浩 岡山大学循環器内科

著者校正/監修レビュー済:2021/09/29
参考ガイドライン:
  1. 日本循環器学会:冠攣縮性狭心症の診断と治療に関するガイドライン(2013年改訂版)
  1. 日本循環器学会:慢性冠動脈疾患診断ガイドライン(2018年改訂版)
  1. 日本循環器学会/日本不整脈心電学会合同ガイドライン:不整脈非薬物治療ガイドライン(2018年改訂版)
患者向け説明資料

概要・推奨   

  1. 冠攣縮発作時には、12誘導心電図の記録とともに、速効性硝酸薬を投与し、発作の軽減に努めることが推奨される(推奨度1)。
  1. 異型狭心症患者の66.7%に無症候性冠攣縮発作が認められる。24時間ホルター心電図によるST上昇、下降の有無の確認と発作時間に合わせた薬物治療が勧められる(推奨度1)。
  1. 有意な器質的冠動脈狭窄を有する冠攣縮性狭心症患者には、Ca拮抗薬あるいは硝酸薬と、β遮断薬を併用し、症状が安定した時点で経皮的冠動脈インターベンション(PCI)に移行することが勧められる(推奨度1)。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧に
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
海北幸一 : 講演料(バイエル薬品),研究費・助成金など(バイエル薬品,第一三共)[2021年]
小川久雄 : 未申告[2021年]
監修:伊藤浩 : 講演料(第一三共,興和,アストラゼネカ,小野,ノバルティスファーマ),研究費・助成金など(興和,Canon),奨学(奨励)寄付など(第一三共,田辺三菱,小野薬品,興和,Boston,武田,ベーリンガーインゲルハイム,持田,バイエル),企業などが提供する寄付講座(日本メドトロニック)[2021年]

改訂のポイント:
  1. 薬物誘発負荷試験に関しては、慢性冠動脈疾患診断ガイドライン(2018年改訂版)に準じて改訂した。近年、公表された文献を参考にして、必要に応じて加筆修正を検討した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 冠攣縮とは、心臓の表面を走行する比較的太い冠動脈が一過性に異常に収縮した状態と定義され、冠攣縮により生じる狭心症を冠攣縮性狭心症という[1]
  1. 冠攣縮性狭心症は、欧米人に比べて日本人の発症率が高く[2]、重要な環境因子は喫煙であることがすでに報告されているが[3]、こうした生活習慣に加えて遺伝的な背景が関与することにより、発症の地域差、民族差が生じていると考えられる[4][5]
  1. 冠攣縮性狭心症の生命予後は、一般によいとされているが、冠動脈の器質的狭窄に冠攣縮を合併した場合や冠攣縮が不安定化した場合には、急性心筋梗塞や突然死を起こすことが知られている[6][7]
  1. 冠攣縮は、冠動脈局所の収縮能の亢進が原因であり、これには、内皮機能不全と血管平滑筋の過収縮の両方が関与していると考えられている[8][9]
  1. 治療は、禁煙などの生活習慣の是正や、Ca拮抗薬、硝酸薬などが有効であるが、まれにこれらの治療を十分に行っても発作を抑制できない難治例がある[6][7][10]
 
  1. 心筋梗塞や狭心症といった虚血性心疾患の発症率には地域差、民族差が存在することが知られている(推奨度1)。
  1. まとめ、代表事例:急性心筋梗塞発症2週間後に冠攣縮薬物誘発試験を実施した国際共同研究(日本人、イタリア人)では、欧米人の冠攣縮陽性率が37%であったのに対し、日本人では80%が陽性であった。この人種差はほかの研究でも再現性をもって認められており、冠攣縮が日本人の虚血性心疾患発症に大きく関与していることが強く示唆される。
  1. 結論:一般に虚血性心疾患の発症頻度は欧米人で高く、日本人を含むアジア人では比較的少ないとされているが、冠攣縮性狭心症においては、欧米人に比べて日本人の発症率が高い[2]
問診・診察のポイント  
  1. 狭心症発作の特徴について確認する。

今なら12か月分の料金で14ヶ月利用できます(個人契約、期間限定キャンペーン)

11月30日(火)までにお申込みいただくと、
通常12ヵ月の使用期間が2ヶ月延長となり、14ヵ月ご利用いただけるようになります。

詳しくはクリック
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: C Pristipino, J F Beltrame, M L Finocchiaro, R Hattori, M Fujita, R Mongiardo, D Cianflone, T Sanna, S Sasayama, A Maseri
雑誌名: Circulation. 2000 Mar 14;101(10):1102-8.
Abstract/Text BACKGROUND: Enhanced coronary vasomotion may contribute to acute coronary occlusion during the acute phase of myocardial infarction (AMI). Japanese have a higher incidence of variant angina than Caucasian patients, but racial differences in vasomotor reactivity early after AMI are controversial.
METHODS AND RESULTS: The same team studied 15 Japanese and 19 Caucasian patients within 14 days of AMI by acetylcholine injection into non-infarct-related (NIRA) and infarct-related (IRA) coronary arteries followed by nitroglycerin. Incidence of vasodilation, vasoconstriction, spasm, and basal tone were assessed in proximal, middle, and distal segments after each drug bolus by quantitative angiography. Japanese patients had much lower cholesterol levels than Caucasians (183+/-59 versus 247+/-53 mg/dL, P<0.006) but showed a lower incidence of vasodilation (2% versus 9% of coronary segments) and a greater incidence of spasm after acetylcholine (47% versus 15% of arteries, P<0.00001). Incidence of spasm was higher in IRAs than in NIRAs in both populations (67% versus 39% and 23% versus 11%, respectively). Multivessel spasm was more common (64% versus 17%, P<0.02) and vasoconstriction of nonspastic segments was greater in Japanese patients (-23.4+/-14.9% versus -20.1+/-15.7%, P<0.02) in the presence of similar average basal coronary tone with respect to post-nitroglycerin dilation and of nonsignificant differences of coronary atherosclerotic score.
CONCLUSIONS: Soon after AMI, Japanese patients exhibited a 3-fold-greater incidence of spasm and greater vasoconstriction of nonspastic segments after acetylcholine than Caucasians. The causes of such differences warrant further investigation because they may have relevant pathophysiological and therapeutic implications.

PMID 10715255  Circulation. 2000 Mar 14;101(10):1102-8.
著者: M Sugiishi, F Takatsu
雑誌名: Circulation. 1993 Jan;87(1):76-9.
Abstract/Text BACKGROUND: Although there have been many studies on the risk factors for coronary artery disease, the etiology of coronary artery spasm has not yet been determined.
METHODS AND RESULTS: After diagnosis by coronary arteriography, various risk factors were compared between two groups of subjects using logistic regression analysis. The vasospasm group included 175 patients with angiographically determined coronary artery spasm but no coronary artery narrowing exceeding 25% of the luminal diameter. The control group comprised 176 subjects with completely normal coronary arteries and a negative response to ergonovine maleate. The adjusted odds ratio and 95% confidence interval for smoking as a risk factor for vasospasm was 2.41 and 1.53-3.82, respectively (p < 0.05). The adjusted odds ratios for total cholesterol, low density lipoprotein, high density lipoprotein, triglycerides, diabetes mellitus, and body mass index, calculated by multivariate logistic regression analysis, were not statistically nonsignificant.
CONCLUSIONS: Smoking appears to be a major risk factor for vasospastic angina without significant coronary narrowing. The other risk factors for coronary artery disease may not contribute to coronary vasospasm.

PMID 8419026  Circulation. 1993 Jan;87(1):76-9.
著者: M Yoshimura, H Yasue, M Nakayama, Y Shimasaki, H Sumida, S Sugiyama, K Kugiyama, H Ogawa, Y Ogawa, Y Saito, Y Miyamoto, K Nakao
雑誌名: Hum Genet. 1998 Jul;103(1):65-9.
Abstract/Text Coronary spasm plays an important role in the pathogenesis of not only variant angina but also ischemic heart disease in general. However, the precise mechanism(s) by which coronary spasm occurs remains to be elucidated. Coronary spasm may arise from interactions between environmental and genetic factors. Endothelial-derived nitric oxide (NO) has been implicated in the control of vascular tone. We have recently shown that both basal and acetylcholine (ACh)-induced NO activities are impaired in the coronary arteries of patients with coronary spasm. The purpose of this study has been to elucidate the possible variants that occur in the coding region of the endothelial nitric oxide synthase (eNOS) gene and that may be associated with coronary spasm. After initial screening in the entire 26 coding regions of the eNOS gene, we found a missense Glu298Asp variant in exon 7 in patients with coronary spasm. We subsequently performed a larger scale study involving 113 patients with coronary spasm and 100 control subjects, who were all diagnosed by intracoronary injection of ACh. The analysis revealed a significant difference in the distribution of the variant between the coronary spasm group (21.2%) and control group (9.0%; P=0.014 for dominant effect). Thus, we have found the missense Glu298Asp variant in the eNOS gene by the analysis of its entire 26 coding regions. The variant is significantly associated with coronary spasm.

PMID 9737779  Hum Genet. 1998 Jul;103(1):65-9.
著者: M Nakayama, H Yasue, M Yoshimura, Y Shimasaki, K Kugiyama, H Ogawa, T Motoyama, Y Saito, Y Ogawa, Y Miyamoto, K Nakao
雑誌名: Circulation. 1999 Jun 8;99(22):2864-70.
Abstract/Text BACKGROUND: Coronary spasm plays an important role in the pathogenesis of ischemic heart diseases in general. However, the precise mechanism(s) responsible for coronary spasm remains to be elucidated, and we examined the molecular genetics of coronary spasm.
METHODS AND RESULTS: We searched for the possible mutations in the endothelial nitric oxide synthase (eNOS) gene in patients with coronary spasm. In this study, we demonstrate the existence of 3 linked mutations in the 5'-flanking region of the eNOS gene (T-786-->C, A-922-->G, and T-1468-->A). The incidence of the mutations was significantly greater in patients with coronary spasm than in the control group (P<0.0001). Multiple logistic regression analysis with forward stepwise selection using the environmental risk factors and the eNOS gene variant revealed that the most predictive independent risk factor for coronary spasm was the mutant allele (P<0.0001). As assessed by luciferase reporter gene assays, the T-786-->C mutation resulted in a significant reduction in eNOS gene promoter activity (P<0.05), whereas neither the A-922-->G nor the T-1468-->A mutation had any affect.
CONCLUSIONS: Taken together, these findings strongly suggest that the T-786-->C mutation in the eNOS gene reduces the endothelial NO synthesis and predisposes the patients with the mutation to coronary spasm.

PMID 10359729  Circulation. 1999 Jun 8;99(22):2864-70.
著者: M Nakamura, A Takeshita, Y Nose
雑誌名: Circulation. 1987 Jun;75(6):1110-6.
Abstract/Text A total of 349 patients with vasospastic angina were followed in eight centers in Japan for a period of 3.4 +/- 0.1 years (mean +/- SE). Ninety-eight percent of patients were treated with calcium blockers. Twenty-one episodes of myocardial infarction occurred in 18 patients (5%), including two fatal myocardial infarctions. The rate of myocardial infarction was higher (p less than .01) in patients with a fixed stenosis of 90% or greater than in patients with a fixed stenosis of less than 90% or normal coronary arteries. Myocardial infarctions occurred predominantly during hospital stays or at a time when the frequency of vasospastic angina increased. There were five sudden deaths (2%). Only one patient suffering sudden death had a fixed stenosis of 75% or greater. Serious arrhythmias were noted in 49 patients (14%). The risk of arrhythmias did not depend on the presence of a fixed stenosis of 75% or greater. These results suggest that cardiac events are rather infrequent in Japanese patients with vasospastic angina who are receiving treatment with calcium blockers and that the presence of a severe fixed stenosis markedly increases the risk of myocardial infarction but not the risk of arrhythmias.

PMID 3568322  Circulation. 1987 Jun;75(6):1110-6.
著者: H Yasue, A Takizawa, M Nagao, S Nishida, M Horie, J Kubota, S Omote, K Takaoka, K Okumura
雑誌名: Circulation. 1988 Jul;78(1):1-9.
Abstract/Text Two hundred forty-five patients with variant angina were followed for an average of 80.5 months (range, 36-184 months). Survival rate at 1, 3, 5, and 10 years was 98%, 97%, 97%, and 93%, respectively. Survival rate without myocardial infarction at 1, 3, 5, and 10 years was 86%, 85%, 83%, and 81%, respectively. By univarite analysis, ST segment elevation in both the anterior and inferior electrocardiographic leads was the most important factor influencing survival, followed by use of calcium antagonists, left ventricular function, smoking, and alcohol intake. The variables that significantly correlated with survival without myocardial infarction were use of calcium antagonists, left ventricular function, extent and severity of coronary artery disease, coronary artery bypass surgery, and disease activity. Multivariate analysis using the Cox proportional hazards model showed that intake of calcium antagonists, extent and severity of coronary artery disease, and ST segment elevation in both the anterior and inferior leads were significant independent predictors of survival without myocardial infarction. We conclude that long-term prognosis for patients with variant angina is relatively good and that use of calcium antagonists improves it.

PMID 3260150  Circulation. 1988 Jul;78(1):1-9.
著者: K Kugiyama, H Yasue, K Okumura, H Ogawa, K Fujimoto, K Nakao, M Yoshimura, T Motoyama, Y Inobe, H Kawano
雑誌名: Circulation. 1996 Aug 1;94(3):266-71.
Abstract/Text BACKGROUND: Coronary spasm can be induced by acetylcholine, serotonin, ergonovine, or histamine, all of which cause vasodilation when the endothelium is intact by releasing nitric oxide (NO). Coronary spasm is promptly relieved by nitroglycerin, which vasodilates through its conversion to NO. It is thus possible that NO release may be deficient in the spasm arteries in patients with coronary spastic angina (CSA). The aim of this study was to determine whether NO release is deficient in coronary arteries of patients with CSA.
METHODS AND RESULTS: NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase, was infused into coronary arteries in 21 patients with coronary spastic angina (CSA) and in 28 control patients. Coronary spasm was induced by intracoronary injection of acetylcholine and was documented angiographically in all patients with CSA. L-NMMA dose-dependently decreased basal luminal diameter of coronary arteries in control patients, whereas it had no effect on basal diameter of the spasm arteries in patients with CSA. L-NMMA abolished the dilator response to acetylcholine and enhanced the constrictor response to acetylcholine in control arteries, whereas it had no effect on the constrictor response to acetylcholine in spasm arteries. Intracoronary infusion of L-arginine did not affect the diameter of spasm or control arteries. The dilator response to nitroglycerin was increased markedly in spasm arteries compared with control arteries, whereas response to diltiazem did not differ between them.
CONCLUSIONS: There is a deficiency in endothelial NO activity in spasm arteries, which leads to the supersensitivity of the artery to the vasodilator effect of nitroglycerin and to the vasoconstrictor effect of acetylcholine in patients with CSA. This deficient endothelial NO activity plays an important role in the pathogenesis of coronary spasm.

PMID 8759065  Circulation. 1996 Aug 1;94(3):266-71.
著者: N Katsumata, H Shimokawa, M Seto, T Kozai, T Yamawaki, K Kuwata, K Egashira, I Ikegaki, T Asano, Y Sasaki, A Takeshita
雑誌名: Circulation. 1997 Dec 16;96(12):4357-63.
Abstract/Text BACKGROUND: Although coronary artery spasm plays an important role in a wide variety of ischemic heart diseases, the intracellular mechanism for the spasm remains to be clarified. We examined the role of myosin light chain (MLC) phosphorylations, a key mechanism for contraction of vascular smooth muscle, in our swine model with interleukin-1beta (IL-1beta).
METHODS AND RESULTS: IL-1beta was applied chronically to the porcine coronary arteries from the adventitia to induce an inflammatory/proliferative lesion. Two weeks after the operation, intracoronary serotonin repeatedly induced coronary hyperconstrictions at the IL-1beta-treated site both in vivo and in vitro, which were markedly inhibited by fasudil, an inhibitor of protein kinases, including protein kinase C and MLC kinase. Western blot analysis showed that during serotonin-induced contractions, MLC monophosphorylation was significantly increased and sustained in the spastic segment compared with the control segment, whereas MLC diphosphorylation was noted only in the spastic segment. A significant correlation was noted between the serotonin-induced contractions and MLC phosphorylations. Both types of MLC phosphorylation were markedly inhibited by fasudil. In addition, MLC diphosphorylation was never induced by a simple endothelium removal in the normal coronary artery, whereas enhanced MLC phosphorylations in the spastic segment were noted regardless of the presence or absence of the endothelium.
CONCLUSIONS: These results indicate that enhanced MLC phosphorylations in the vascular smooth muscle play a central role in the pathogenesis of coronary spasm in our swine model.

PMID 9416904  Circulation. 1997 Dec 16;96(12):4357-63.
著者: H Shimokawa, K Nagasawa, T Irie, S Egashira, K Egashira, T Sagara, Y Kikuchi, M Nakamura
雑誌名: Int J Cardiol. 1988 Mar;18(3):331-49.
Abstract/Text To determine the factors influencing the prognosis of variant angina, the clinical characteristics and long-term prognosis of 158 consecutive Japanese patients were examined and compared with those in previous major western studies (Pisa, Montreal, and Duke studies). The Japanese patients were characterized by relatively low prevalences of coronary risk factors, significant coronary stenoses and previous myocardial infarction. Survival and survival without myocardial infarction for the entire group or for the subpopulation with significant coronary artery disease were significantly better in the Japanese population than in the western populations; however, in the subpopulation without significant coronary artery disease, the prognosis was excellent in all four studies. If the prevalence of coronary artery disease was corrected for the Japanese population, there would be no difference in the prognosis between the Japanese and the western populations. It is concluded: (1) the overall prognosis of variant angina may be better in Japanese patients, and (2) coronary artery disease appears to be the strongest prognostic factor for assessing the differences in the prognosis between the Japanese and the western populations.

PMID 3129375  Int J Cardiol. 1988 Mar;18(3):331-49.
著者: H Yasue, K Kugiyama
雑誌名: Intern Med. 1997 Nov;36(11):760-5.
Abstract/Text Coronary artery spasm (coronary spasm) is an abnormal contraction of an epicardial coronary artery resulting in myocardial ischemia and its incidence is relatively high in Japanese as compared with Caucasians. Coronary spasm occurs most often from midnight to early morning when the patient is at rest and it is usually not induced by exercise in the daytime. Coronary spasm can be induced by acetylcholine, an endothelium-dependent vasodilator which causes vasodilatation in the normal coronary artery. Spasm artery is hyperresponsive to the vasodilator effect of nitroglycerin, an nitric oxide (NO) donor and is deficient in NO activity. The major risk factor for coronary spasm is cigarette smoking. Coronary spasm can be a cause of not only variant angina but also ischemic heart disease in general, including unstable angina, acute myocardial infarction and sudden ischemic death.

PMID 9392345  Intern Med. 1997 Nov;36(11):760-5.
著者: K Nakao, M Ohgushi, M Yoshimura, K Morooka, K Okumura, H Ogawa, K Kugiyama, Y Oike, K Fujimoto, H Yasue
雑誌名: Am J Cardiol. 1997 Sep 1;80(5):545-9.
Abstract/Text The hyperventilation test has been used as a clinical tool to induce coronary spasm. However, its diagnostic and prognostic values have not been fully elucidated. This study was designed to establish the sensitivity and specificity of the hyperventilation test and to clarify the characteristics of hyperventilation test-positive patients. We examined 206 patients in whom coronary spasm was documented by angiography (spasm group), and 183 patients without angina at rest in whom acetylcholine failed to induce spasm (nonspasm group). All patients performed vigorous hyperventilation for 6 minutes in the early morning. Of the spasm group patients, 127 showed positive responses to the test, including ST elevation (n = 111), ST depression (n = 15) and negative U wave (n = 1). None in the nonspasm group showed any ischemic electrocardiographic change. Thus, the sensitivity and specificity of this test for diagnosis of coronary spasm were 62% and 100%, respectively. In the spasm group, there were no significant differences between hyperventilation test-positive and test-negative patients in age, sex, the prevalence of hypertension, diabetes mellitus, obesity, smoking, and the number of diseased vessels. When clinical characteristics were compared, the proportions of the patients with high disease activity (> or =5 attacks a week), with severe arrhythmias (second- or third-degree atrioventricular block and/or ventricular tachycardia) during attacks, and with multivessel spasm were significantly higher in the hyperventilation test-positive patients than in the negative patients (69% vs 20%, p <0.0001; 31% vs 11%, p <0.005; and 58% vs 34%, p <0.01, respectively). These findings imply that hyperventilation is a highly specific test for the diagnosis of coronary artery spasm, and that hyperventilation test-positive patients are likely to have life-threatening arrhythmias during attacks and multivessel spasm.

PMID 9294979  Am J Cardiol. 1997 Sep 1;80(5):545-9.
著者: K Okumura, H Yasue, K Matsuyama, K Goto, H Miyagi, H Ogawa, K Matsuyama
雑誌名: J Am Coll Cardiol. 1988 Oct;12(4):883-8.
Abstract/Text Intracoronary injection of acetylcholine has been shown to induce coronary spasm in patients with variant angina. To examine its sensitivity and specificity, incremental doses of acetylcholine (20, 50 and 100 micrograms into the left coronary artery and 20 and 50 micrograms into the right coronary artery) were injected into the coronary artery or arteries in 70 patients with variant angina (Group 1) (mean age 57 years) and 93 patients without variant angina or angina at rest (Group 2) (mean age 54 years). Forty patients of the latter group had atypical chest pain, 16 cardiomyopathy, 14 arrhythmia, 11 valvular disease, 7 stable effort angina due to advanced coronary artery disease, 3 congenital heart disease and 2 hypertension. A temporary cardiac pacemaker set at 40 to 50 beats/min was positioned in the right ventricle. Coronary spasm was defined as total occlusion or severe vasoconstriction associated with chest pain or ischemic ST changes on the electrocardiogram or both. In Group 1, acetylcholine induced spasm in 63 (90%) of the 70 patients in the artery or arteries predicted to be responsible for spontaneous attacks. In Group 2, acetylcholine induced coronary spasm only in one patient with effort angina and advanced coronary artery disease although lesser degrees of vasoconstriction (less than or equal to 75% of the luminal diameter) occurred in most patients after acetylcholine (specificity of acetylcholine thus was 99%). In conclusion, intracoronary injection of acetylcholine is sensitive and reliable for the induction of coronary spasm.

PMID 3047196  J Am Coll Cardiol. 1988 Oct;12(4):883-8.
著者: S Sueda, N Ochi, H Kawada, S Matsuda, Y Hayashi, T Tsuruoka, T Uraoka
雑誌名: Am J Cardiol. 1999 Apr 15;83(8):1186-90.
Abstract/Text This study examines the incidence of spasm by intracoronary injection of acetylcholine in Japanese patients who underwent coronary angiography. The subjects were 685 consecutive patients (477 men, mean age 63.2 +/- 7.5 years) who were studied with an acetylcholine test. Acetylcholine was injected in incremental doses of 20, 50, and 80 microg into the right coronary artery and 20, 50, and 100 microg into the left coronary artery. Spasm was defined as total or subtotal occlusion. Coronary vasospasm was determined in 221 patients (32.3%). Spasm occurred often during effort and rest in patients with angina (25 of 51, 49.0%), exertional angina (25 of 74, 33.8%), recent myocardial infarction (30 of 80, 37.5%), healed myocardial infarction (14 of 37, 37.8%), and especially in patients with rest angina (83 of 124, 66.9%), whereas spasm was relatively uncommon in patients with nonischemic heart disease (23 of 252, 9.1%). Spasm was superimposed on significant atherosclerotic lesions in 35.9% of patients as well as on nonfixed atherosclerotic lesions in 30.8% of patients. We conclude that >9% of Japanese patients may have coronary vasospasm with intracoronary injection of acetylcholine and recommend the provocation test for evaluating coronary vasospasm if coronary angiography is undertaken.

PMID 10215281  Am J Cardiol. 1999 Apr 15;83(8):1186-90.
著者: K Okumura, H Yasue, K Matsuyama, H Ogawa, Y Morikami, K Obata, N Sakaino
雑誌名: J Am Coll Cardiol. 1992 Mar 15;19(4):752-8.
Abstract/Text To examine the constrictor response of the infarct-related stenotic coronary artery in comparison with that of noninfarct-related stenotic arteries, acetylcholine in maximal doses of 100 micrograms for the left and 50 micrograms for the right coronary artery was injected into the 16 infarct-related coronary arteries of 16 patients with previous myocardial infarction (group 1) and into 19 stenotic coronary arteries of 16 patients with stable angina without myocardial infarction (group 2). Acetylcholine's effects on lumen diameter and area were quantitatively analyzed at the stenotic segment and its proximal segment without significant stenosis. Acetylcholine decreased lumen diameter and area at the stenotic segments from 0.72 +/- 0.18 to 0.18 +/- 0.33 mm and from 0.45 +/- 0.22 to 0.10 +/- 0.22 mm2, respectively, in group 1 (both p less than 0.01) and from 0.75 +/- 0.22 to 0.49 +/- 0.30 mm and 0.48 +/- 0.29 to 0.26 +/- 0.23 mm2, respectively, in group 2 (both p less than 0.01). Acetylcholine decreased the diameter and area at the proximal segment from 2.71 +/- 0.75 to 2.38 +/- 0.6 mm and from 6.18 +/- 3.4 to 4.71 +/- 2.23 mm2, respectively, in group 1 (both p less than 0.01) and from 2.31 +/- 0.67 to 1.95 +/- 0.59 mm and from 4.5 +/- 2.97 to 3.22 +/- 1.96 mm2, respectively, in group 2 (both p less than 0.01). The changes in diameter and area at the stenotic segment in group 1 were significantly greater than those in group 2 (both p less than 0.01); there were no significant differences between groups in the changes at the proximal segment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 1545069  J Am Coll Cardiol. 1992 Mar 15;19(4):752-8.
著者: Shozo Sueda, Yousuke Izoe, Hiroaki Kohno, Hiroshi Fukuda, Tadao Uraoka
雑誌名: Circ J. 2005 Nov;69(11):1333-7.
Abstract/Text BACKGROUND: Because there are no guidelines concerning coronary spasm in Japan, the present study examined the current status of the spasm provocation test.
METHODS AND RESULTS: Questionnaires concerning the number of cases of coronary angiography, percutaneous coronary intervention, and invasive/non-invasive spasm provocation tests over 3 years (2001-2003) and the status of spasm provocation tests were sent to members of the Japanese Circulation Society in 120 cardiology hospitals in the Chugoku and Shikoku areas. Completed surveys were returned from 45 hospitals, giving a collection rate of 38%. As a spasm provocation agent, acetylcholine tests were performed in 29 hospitals, and ergonovine tests in 18 hospitals. Non-invasive spasm provocation tests were performed in only 9 hospitals (20%). In total, 5,267 patients underwent acetylcholine spasm provocation test (2,387 patients) or ergonovine spasm provocation test (2,880 patients) and vasospastic angina was diagnosed in 1,663 (2.4%) patients. Invasive spasm provocation tests were performed in 7.8% of patients with diagnostic catheterization and the spasm-positive rate was 31.6%. The difference among hospitals concerning the number of invasive spasm provocation tests was remarkable, and the angiographic spasm-positive standard and acetylcholine/ergonovine dose varied among the hospitals.
CONCLUSIONS: Guidelines on coronary spasm in Japan are essential to overcome the current differences between institutions.

PMID 16247207  Circ J. 2005 Nov;69(11):1333-7.
著者: M Mohri, M Koyanagi, K Egashira, H Tagawa, T Ichiki, H Shimokawa, A Takeshita
雑誌名: Lancet. 1998 Apr 18;351(9110):1165-9. doi: 10.1016/S0140-6736(97)07329-7.
Abstract/Text BACKGROUND: Microvascular angina can occur during exercise and at rest. Reduced vasodilator capacity of the coronary microvessels is implicated as a cause of angina during exercise, but the mechanism of angina at rest is not known. Our aim was to test the hypothesis that primary hyperconstriction (spasm) of coronary microvessels causes myocardial ischaemia at rest.
METHODS: Acetylcholine induces coronary artery spasm in patients with variant angina. We tested the effects of intracoronary acetylcholine at graded doses in 117 consecutive patients with chest pain (at rest, during exertion, or both) and no flow-limiting (>50%) organic stenosis in the large epicardial coronary arteries. We also assessed the metabolism of myocardial lactate during acetylcholine administration in 36 of the patients by measurement of lactate in paired blood samples from the coronary artery and coronary sinus vein.
FINDINGS: Of the 117 patients, 63 (54%) had large-artery spasm, 29 (25%) had microvascular spasm, and 25 (21%) had atypical chest pain. The 29 patients with microvascular spasm developed angina-like chest pain, ischaemic electrocardiogram (ECG) changes, or both spontaneously (two patients) or after administration of acetylcholine (27 patients) without spasm of the large epicardial coronary arteries. Testing of paired samples of arterial and coronary sinus venous blood showed that lactate was produced during angina attack in nine of 11 patients with microvascular spasm. There was more women (p<0.01) and fewer coronary risk factors (p<0.01) in patients with microvascular spasm than in those with large-artery spasm.
INTERPRETATION: Coronary microvascular spasm and resultant myocardial ischaemia may be the cause of chest pain in a subgroup of patients with microvascular angina.

PMID 9643687  Lancet. 1998 Apr 18;351(9110):1165-9. doi: 10.1016/S014・・・
著者: A Walling, D D Waters, D D Miller, D Roy, G B Pelletier, P Théroux
雑誌名: Circulation. 1987 Nov;76(5):990-7.
Abstract/Text The long-term prognosis of variant angina and the factors influencing it were assessed in 217 consecutive patients hospitalized in our coronary care unit and followed for a mean of 65 months (range 2 to 123). Cardiac death occurred in 30 patients and an additional 54 experienced a nonfatal myocardial infarction. Survival at 1 and 5 years was 95% and 89%, respectively; survival without infarction was 83% and 69%. Coronary disease and the degree of disease activity were strong predictors of survival by Cox analysis. Survival at 1 year was 99%, and that at 5 years was 95% and 94%, respectively, for patients with one-vessel disease (n = 81) and for those without stenoses of 70% or greater (n = 87). Survival at 1 and 5 years was only 87% and 77% for those with multivessel disease (n = 40). The Cox analysis selected left ventricular function, initial treatment, extent score, duration of angina at rest, and disease activity as multivariate predictors of survival without infarction. Coronary disease was a strong predictor (p less than .0001) of survival without infarction by univariate analysis. Treatment with nifedipine, diltiazem, or verapamil improved survival without infarction compared with other medical treatment (p = .002). Myocardial infarction occurred most commonly soon after diagnosis in patients with a short history of angina at rest. Late coronary events were almost never preceded by resting angina.

PMID 3665004  Circulation. 1987 Nov;76(5):990-7.
著者: R A Chahine, R L Feldman, T D Giles, P Nicod, A E Raizner, R J Weiss, S K Vanov
雑誌名: J Am Coll Cardiol. 1993 May;21(6):1365-70.
Abstract/Text OBJECTIVES: This study was designed to assess the efficacy and safety of amlodipine, a long-acting calcium channel blocker, in patients with vasospastic angina.
BACKGROUND: Previous studies have established the value of short-acting calcium channel blockers in the treatment of coronary spasm.
METHODS: Fifty-two patients with well documented vasospastic angina were entered into the present study. After a single-blind placebo run-in period, patients were randomized (in a double-blind protocol) to receive either amlodipine (10 mg) or placebo every morning for 4 weeks. Twenty-four patients received amlodipine and 28 received placebo. All patients were given diaries in which to record both the frequency, severity, duration and circumstances of anginal episodes and their intake of sublingual nitroglycerin tablets.
RESULTS: The rate of anginal episodes decreased significantly (p = 0.009) with amlodipine treatment compared with placebo and the intake of nitroglycerin tablets showed a similar trend. Peripheral edema was the only adverse event seen more frequently in amlodipine-treated patients. No patient was withdrawn from the double-blind phase of the study because of an adverse event. Patients who completed the double-blind phase as responders to amlodipine or as nonresponders to placebo were offered the option of receiving amlodipine in a long-term, open label extension phase. During the extension, the daily dose of amlodipine was adjusted to 5 or 15 mg if needed and the rate of both anginal episodes and nitroglycerin tablet consumption showed statistically significant decreases between baseline and final assessment.
CONCLUSION: This study suggests that amlodipine given once daily is efficacious and safe in the treatment of vasospastic angina.

PMID 8166777  J Am Coll Cardiol. 1993 May;21(6):1365-70.
著者: K Takaoka, M Yoshimura, H Ogawa, K Kugiyama, M Nakayama, Y Shimasaki, Y Mizuno, T Sakamoto, H Yasue
雑誌名: Int J Cardiol. 2000 Jan 15;72(2):121-6.
Abstract/Text We compared the risk factors for coronary spasm with those for coronary atherosclerosis in 183 patients with coronary spasm, 132 patients with coronary organic stenosis, and 224 control subjects with chest pain syndrome. Our findings confirmed that, when compared with controls, age, gender, total cholesterol, LDL-cholesterol, hypertension, diabetes mellitus, and cigarette smoking are all significant risk factors for coronary organic stenosis. On the other hand, only cigarette smoking proved to be a significant risk factor for coronary spasm. Also, when compared between coronary spasm group and coronary organic stenosis group, the incidence of cigarette smoking in males was significantly higher in the coronary spasm group than in the coronary organic stenosis group. We conclude that cigarette smoking is a crucial risk factor for coronary spasm. On the other hand, serum lipid levels and the incidence of hypertension and diabetes mellitus were within the normal ranges in the coronary spasm patients and were thus poorly associated with coronary spasm. These results showed that the risk factors for coronary spasm differ significantly from those for atherosclerosis-based coronary stenosis in the Japanese. Among the risk factors for coronary atherosclerosis (organic stenosis) smoking alone was a significant preventable risk factor for coronary artery spasm.

PMID 10646952  Int J Cardiol. 2000 Jan 15;72(2):121-6.
著者: M Nobuyoshi, M Abe, H Nosaka, T Kimura, H Yokoi, N Hamasaki, T Shindo, K Kimura, T Nakamura, Y Nakagawa
雑誌名: Am Heart J. 1992 Jul;124(1):32-8.
Abstract/Text Coronary artery spasm plays an important role in acute ischemic events, and it has a close relationship with coronary atherosclerosis. Thus we attempted to determine the most significant risk factor for coronary artery spasm. Among 3000 consecutive patients who underwent coronary cineangiography with ergonovine maleate testing, 330 with typical angina pectoris (group 1) and 294 with old myocardial infarction (group 2) were studied. We divided each group into three or four subgroups according to the presence of fixed organic stenosis (FOS+) or a positive reaction to ergonovine maleate (coronary artery spasm [CAS]+). We examined the relationship between coronary artery spasm and eight coronary risk factors: age, sex, hypertension, diabetes mellitus, smoking, and serum cholesterol, uric acid, and high-density lipoprotein cholesterol levels. The proportion of smokers in the subgroups with CAS(+) was significantly higher than in the subgroups with CAS(-)(p less than 0.01). There was no correlation between smoking and fixed organic stenosis. According to the results of multiple regression analysis, there was a positive correlation between smoking and CAS(+) and between serum high-density lipoprotein cholesterol levels and CAS(+)(p less than 0.01). Thus we concluded that smoking is the most significant risk factor in discriminating between patients with and without coronary artery spasm.

PMID 1615825  Am Heart J. 1992 Jul;124(1):32-8.
著者: E G Nabel, P Ganz, J B Gordon, R W Alexander, A P Selwyn
雑誌名: Circulation. 1988 Jan;77(1):43-52.
Abstract/Text Increased vascular constriction has been observed at the site of atherosclerotic lesions, suggesting an association between atherosclerosis and altered vascular tone. While atherosclerosis may increase sensitivity to exogenous vasoconstrictors, little is known about the response of normal and atherosclerotic coronary arteries to an exogenous stimulus that excites the sympathetic nervous system. Therefore, we studied the response to cold pressor test (CPT) using quantitative angiography and Doppler flow velocity measurements in eight patients with angiographically normal coronary arteries (group I), nine patients with mild coronary atherosclerosis (less than 50% diameter narrowing) (group II), and 13 patients with advanced coronary stenoses (greater than 50% diameter narrowing) (group III). In 31 segments of angiographically smooth arteries in group I, the CPT produced vasodilation from a control mean diameter of 2.68 +/- 0.09 (mean +/- SE) to 2.99 +/- 0.09 mm at peak CPT (p less than 0.001), a 12 +/- 1% increase in diameter. In group II, 27 irregular segments constricted to peak CPT from a mean control diameter of 1.82 +/- 0.12 to 1.66 +/- 0.12 mm (p less than .001), a 9 +/- 1% decrease, while 10 smooth segments dilated from a mean control diameter of 1.98 +/- 0.11 mm to 2.34 +/- 0.15 mm (p less than .01), a 19 +/- 2% increase in diameter. Likewise, in group III, the 17 stenotic segments constricted from 1.16 +/- 0.09 to 0.89 +/- 0.09 mm (p less than .001), a 24 +/- 6% decrease; the irregular segments also constricted from 2.44 +/- 0.11 to 2.22 +/- 0.12 mm (p = .002), a 10 +/- 2% decrease. In contrast, two smooth segments dilated from 2.98 to 3.23 mm (mean), an 8% increase in diameter. Coronary blood flow increased 65 +/- 4% (mean) during CPT in group I, it increased 15 +/- 6% in group II, and it decreased 39 +/- 8% in group III. The vasodilator response in four normal patients was partly inhibited by the administration of intracoronary propranolol (17 +/- 3% increase during control, 10 +/- 2% increase after propranolol, 41% less dilation; p = .002). We conclude that the response of normal coronary arteries to the CPT test is dilation, in part related to beta-adrenoreceptor stimulation and possibly flow-mediated endothelial dilation or alpha 2-adrenergic activity. The paradoxical vasoconstrictor response induced by atherosclerosis may represent altered catecholamine sensitivity and/or a defect in endothelial vasodilator function. The presence of atherosclerosis impairs vasodilator responses and thus may contribute to the pathogenesis of myocardial ischemia.

PMID 2826047  Circulation. 1988 Jan;77(1):43-52.
著者: Hirofumi Yasue, Yuji Mizuno, Eisaku Harada, Teruhiko Itoh, Hitoshi Nakagawa, Masafumi Nakayama, Hisao Ogawa, Shinji Tayama, Takasi Honda, Seiji Hokimoto, Shuichi Ohshima, Youichi Hokamura, Kiyotaka Kugiyama, Minoru Horie, Michihiro Yoshimura, Masaki Harada, Shiroh Uemura, Yoshihiko Saito, SCAST (Statin and Coronary Artery Spasm Trial) Investigators
雑誌名: J Am Coll Cardiol. 2008 May 6;51(18):1742-8. doi: 10.1016/j.jacc.2007.12.049.
Abstract/Text OBJECTIVES: The purpose of this study was to determine whether a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) suppresses coronary spasm.
BACKGROUND: Coronary spasm is associated with endothelial dysfunction. Statins have been shown to improve endothelial function.
METHODS: This was a prospective, randomized, open-label, end point study. Sixty-four patients who had no significant organic coronary stenosis and in whom coronary spasm was induced by intracoronary injection of acetylcholine (ACh) were randomly assigned to fluvastatin 30 mg/day plus the conventional calcium-channel blocker (CCB) therapy (31 patients, statin group) or the conventional CCB therapy (33 patients, nonstatin group). After 6 months of treatment, the intracoronary injection of ACh was repeated and the coronary spasm was assessed.
RESULTS: Coronary spasm was suppressed in 16 of the 31 patients (51.5%, p < 0.0001) of the statin group and in 7 of the 33 patients (21.2%, p = 0.0110) of the nonstatin group after 6 months of treatment. Thus, the number of patients with ACh-induced coronary spasm was significantly reduced in the statin group as compared with the nonstatin group (51.6% vs. 21.2%, p = 0.0231) after 6 months of treatment.
CONCLUSIONS: The addition of fluvastatin 30 mg/day to the conventional CCB therapy for 6 months significantly reduced the number of patients with ACh-induced coronary spasm as compared with the conventional CCB therapy. Thus, a statin (fluvastatin) may possibly be a novel therapeutic drug for coronary spasm.

PMID 18452779  J Am Coll Cardiol. 2008 May 6;51(18):1742-8. doi: 10.10・・・
著者: Tomohiro Sakamoto, Yoshitaka Shintomi, Michihiro Yoshimura, Hisao Ogawa
雑誌名: Intern Med. 2007;46(17):1425-9. Epub 2007 Sep 3.
Abstract/Text This case report describes a 78-year-old man with recurrent angina attacks due to coronary spasm. He was treated with maximum daily doses of antianginal and antioxidative medications, including isosorbide mononitrate (40 mg), diltiazem (200 mg), and tocopherol nicotinate (300 mg). Despite the use of these medications, rest angina occurred 2 or 3 times during sleep. Although his symptoms disappeared promptly with the use of sublingual glycerine trinitrate (GTN), an angiotensin II receptor blocker, valsartan (80 mg), was added on a daily basis with the intent of improving endothelial function and controlling his angina. After beginning 80 mg/day of valsartan, the number of the anginal attacks decreased by about 66%. The anginal attacks totally disappeared after the dose of valsartan was increased to 160 mg/day. To confirm the effect of valsartan on his angina, valsartan was stopped temporarily with his consent. His anginal attacks increased to the same frequency that was observed before valsartan; therefore, valsartan therapy was resumed. The data indicate that the addition of valsartan to maximum antianginal medications may be effective in helping to control angina attacks at rest due to coronary spasm.

PMID 17827843  Intern Med. 2007;46(17):1425-9. Epub 2007 Sep 3.
著者: D G Caralis, U Deligonul, M J Kern, J D Cohen
雑誌名: Circulation. 1992 Mar;85(3):905-9.
Abstract/Text BACKGROUND: Risk factors for pure coronary spasm are not known. Clinical observations have pointed to cigarette smoking, a known risk factor for obstructive coronary artery disease.
METHODS AND RESULTS: We conducted a case-neighborhood control study of premenopausal women, a population segment with the lowest prevalence of obstructive coronary artery disease. The cases were 21 premenopausal women (age range, 36-41 years) with angiographically proven coronary spasm. All coronary arteriograms were analyzed by two independent experienced cardiologists on two occasions. There were no differences between analyses; all cases had normal baseline coronary angiogram except for two, who had less than 20% coronary luminal stenosis in segments other than the site of the focal vasospasm. All cases had normal hemodynamics at rest, normal left ventricular function, and were in sinus rhythm. Ascertainment of the cases was done by angiographic demonstration of focal coronary spasm spontaneously or by ergonovine provocation. Six cases developed spontaneous coronary spasm before catheter engagement, and in 15, coronary spasm was induced by ergonovine provocation. Each case was asked to name as many as possible female neighborhood acquaintances of similar age and racial background who were willing to answer the same standardized questionnaire. The same standardized questionnaire was completed for each case and each control (n = 63). The standardized questionnaire was designed to obtain information on health characteristics, habits, socioeconomic status, and education. Only cigarette smoking was significantly more prevalent among coronary spasm cases. Cigarette smokers were 13 cases (62%) and 11 controls (17.5%) (p less than 0.001). The odds ratio was 7.7, with a 95% confidence interval of 2.6-23.1.
CONCLUSIONS: These findings suggest that there is a very strong association between cigarette smoking and pure coronary spasm in young women.

PMID 1537126  Circulation. 1992 Mar;85(3):905-9.
著者: M Lombardi, M A Morales, C Michelassi, E Moscarelli, A Distante, A L'Abbate
雑誌名: Eur Heart J. 1993 Jun;14(6):845-51.
Abstract/Text This study was designed to assess the efficacy of oral nifedipine as compared to oral isosorbide-5-mononitrate in the prevention of spontaneous and induced vasospastic myocardial ischaemia. Twenty-one patients admitted to the Coronary Care Unit as a result of angina at rest underwent both Holter monitoring and an echo-ergonovine test during placebo and following either isosorbide-5-mononitrate or nifedipine according to a double-blind randomized trial. Both drugs caused a statistically significant reduction in spontaneous (87% and 95%, respectively) and induced ischaemic attacks (66% and 75%, respectively). No significant difference was found between the two drugs.

PMID 8325315  Eur Heart J. 1993 Jun;14(6):845-51.
著者: J M Lablanche, C Bauters, F Leroy, M E Bertrand
雑誌名: J Cardiovasc Pharmacol. 1992;20 Suppl 3:S82-5.
Abstract/Text The efficacy of nicorandil was compared with that of nifedipine in 13 patients with vasospastic angina enrolled in a randomized, placebo-controlled, crossover study. All patients had a coronary spasm during coronary arteriography, either spontaneously or ergometrine-induced. During two consecutive periods of 2 days, patients received active drugs or placebo in a randomized order. Each patient received single oral doses of 30 mg nicorandil, 10 mg nifedipine, and, on 2 days, a placebo. One hour after drug intake, patients underwent an ergometrine test with increasing doses of Methergin (ergometrine) (0.05, 0.10, 0.20, and 0.40 mg every 5 min). After placebo, the tests always were positive, and the ECG changes occurred at the same +/- 1 dose of ergometrine in 10 cases, showing good reproducibility. After nicorandil, the tests were negative in nine patients and positive for a higher or lower dose of ergometrine in three and one patient, respectively (p = 0.0034 vs. placebo). After nifedipine, the tests were negative in five patients and positive for a higher or the same dose of ergometrine in four and four patients, respectively (p = 0.0039 vs. placebo). Nifedipine (10 mg) and nicorandil (30 mg) were equally effective in eight patients; in the remaining five patients, nicorandil had better results (p = 0.06). Nicorandil (30 mg) prevents ergometrine-induced coronary spasm. This compound may be beneficial in patients with vasospastic angina.

PMID 1282182  J Cardiovasc Pharmacol. 1992;20 Suppl 3:S82-5.
著者: Simcha R Meisel, Alex Mazur, Israel Chetboun, Menashe Epshtein, Menahem Canetti, Jacob Gallimidi, Amos Katz, Boris Strasberg, Benny Peled
雑誌名: Am J Cardiol. 2002 May 1;89(9):1114-6.
Abstract/Text
PMID 11988204  Am J Cardiol. 2002 May 1;89(9):1114-6.
著者: P Chevalier, A Dacosta, P Defaye, T Chalvidan, E Bonnefoy, G Kirkorian, K Isaaz, B Denis, P Touboul
雑誌名: J Am Coll Cardiol. 1998 Jan;31(1):57-61.
Abstract/Text OBJECTIVES: Our aim was to look at the clinical features and long-term follow-up of seven patients without coronary artery disease, who had a history of life-threatening ventricular arrhythmias due to coronary spasm.
BACKGROUND: Arrhythmic cardiac arrest due to isolated coronary spasm is rare, and there is limited information on the patients affected by this entity alone.
METHODS: The seven patients were recruited retrospectively from a cohort of survivors of cardiac arrest. None had a history of angina pectoris, structural heart disease or significantly narrowed coronary segments. All had a positive ergonovine provocation test result.
RESULTS: The patients' mean age was 44 years; three were male and four female. All were habitual cigarette smokers. No arrhythmias were induced on programmed ventricular stimulation; corrected QT interval (QTc) and corrected JT interval (JTc) dispersion were within normal ranges. After the ergonovine provocation test, treatment with calcium channel blocking agents (diltiazem, verapamil, nifedipine or amlodipine) was initiated at a dose determined by titration until a negative test result was obtained. At a mean follow-up interval of 58 months for the total group, six patients remained free of symptoms, whereas the one patient who did not stop smoking had a new cardiac arrest despite treatment for coronary spasm.
CONCLUSIONS: A favorable long-term outcome may be expected in survivors of cardiac arrest due to coronary spasm, in the absence of significant coronary artery disease. Calcium channel blockers are the most appropriate therapy in these patients. These observations provide further evidence for the role of silent ischemia in cardiovascular death.

PMID 9426018  J Am Coll Cardiol. 1998 Jan;31(1):57-61.
著者: Yuya Matsue, Makoto Suzuki, Mitsuhiro Nishizaki, Rintaro Hojo, Yuji Hashimoto, Harumizu Sakurada
雑誌名: J Am Coll Cardiol. 2012 Sep 4;60(10):908-13. doi: 10.1016/j.jacc.2012.03.070. Epub 2012 Jul 25.
Abstract/Text OBJECTIVES: The present study was performed to investigate the clinical implications of an implantable cardioverter-defibrillator (ICD) in patients with vasospastic angina (VSA) resuscitated from lethal ventricular arrhythmia.
BACKGROUND: The prognosis of VSA is known to be good with medication; however, ventricular arrhythmia and cardiopulmonary arrest are rare but life-threatening complications of this disease. The ICD is a proven modality for patients with ventricular arrhythmia, but the clinical implications in this population remain to be elucidated.
METHODS: We conducted a retrospective, observational, multicenter study involving patients with an ICD due to documented ventricular arrhythmia and VSA diagnosed by acetylcholine provocation test. All patients were followed up for appropriate ICD therapy, sudden cardiac arrest, or death from all causes.
RESULTS: Twenty-three patients were included in the present study and completely followed up. All patients are still alive. During a follow-up of 2.9 years (median 2.1 years), 4 ventricular fibrillations and 1 episode of pulseless electrical activity occurred in 5 patients (21.7%). There were no statistically significant differences in patient characteristics between the recurrence and nonrecurrence groups, including medication, smoking status, and whether the patient was or was not free of symptoms after ICD implantation.
CONCLUSIONS: Patients with VSA and lethal ventricular arrhythmia are a population at high risk for recurrence of cardiopulmonary arrest, and there is no reliable indicator for predicting recurrence of ventricular arrhythmia. Insertion of an ICD with medication for VSA is appropriate for this high-risk population.

Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PMID 22840527  J Am Coll Cardiol. 2012 Sep 4;60(10):908-13. doi: 10.10・・・
著者: E C Schick, C S Liang, F A Heupler, F R Kahl, K M Kent, N Z Kerin, R J Noble, M Rubenfire, B Tabatznik, R W Terry
雑誌名: Am Heart J. 1982 Sep;104(3):690-7.
Abstract/Text A multicenter randomized double-blind withdrawal study was conducted to compare the efficacy of nifedipine to that of placebo in vasospastic angina. Following a 2-week single-blind nifedipine baseline period, during which nifedipine was maintained at prestudy levels, 38 patients, 19 taking placebo and 19 continuing nifedipine therapy, either completed a 4-week randomized phase or were prematurely withdrawn because of therapeutic failure. During the randomized phase, an increase in median anginal frequency (2.8 attacks/wk, p less than 0.003) and nitroglycerin usage (0.5 tablets/wk, p less than 0.03) occurred only in the placebo group. The randomized phase was prematurely terminated because of anginal exacerbation in 7 of 19 placebo patients (37%) (only 1 patient receiving nifedipine [p = 0.02] experienced anginal exacerbation). Double-blind therapy was judged effective in 16 patients (84%) receiving nifedipine and in 3 patients (16%) receiving placebo (p less than 0.001). Nifedipine was well tolerated. This study establishes the efficacy of nifedipine in the treatment of variant and validates previous clinical experience.

PMID 6810682  Am Heart J. 1982 Sep;104(3):690-7.

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから