Clinical Implications of Provocation Tests of Coronary Artery Spasm:

Transcription

1 Clinical Implications of Provocation Tests of Coronary Artery Spasm: Safety, Arrhythmic Complication and Type of Spasm - A Report from the Nationwide Multicenter Registry by the Japanese Coronary Spasm Association - Yusuke Takagi, Satoshi Yasuda, Ryusuke Tsunoda, Yasuhiro Ogata, Atsushi Seki, Tetsuya Sumiyoshi, Motoyuki Matsui, Toshikazu Goto, Yasuhiro Tanabe, Shozo Sueda, Toshiaki Sato, Satoshi Ogawa, Norifumi Kubo, Shin-ichi Momomura, Hisao Ogawa, Hiroaki Shimokawa, on Behalf of the Japanese Coronary Spasm Association

2 Presenter Disclosure Information Yusuke Takagi, MD Clinical Implications of Provocation Tests of Coronary Artery Spasm: Safety, Arrhythmic Complication and Type of Spasm -A Report from the Nationwide Multicenter Registry by the Japanese Coronary Spasm Association- FINANCIAL DISCLOSURE: Grants/Research Support: The Japan Heart Foundation Speakers Bureau: Tohoku University Graduate School of Medicine UNLABELED/UNAPPROVED USES DISCLOSURE: None

3 Background Provocation tests of coronary artery spasm are useful for diagnosis of vasospastic angina (VSA). These tests have a potential risk of arrhythmic complications including ventricular tachycardia (VT), ventricular fibrillation (VF) and brady-arrhythmias. Control Acetylcholine VF during prov. test

4 Purpose We evaluated 1) the incidence and the prognostic impact of arrhythmic complications 2) the angiographic findings which correlated with patient prognosis in the nationwide multicenter registry study by the Japanese Coronary Spasm Association. 75 Institutes in the Japanese Coronary Spasm Association

5 Methods

6 Study patients VSA patients originally diagnosed between April, 2003 and December, 2008 were retrospectively registered from 47 institutes.

7 Diagnostic criteria On the basis of Guidelines for Diagnosis and Treatment of Patients with Vasospastic Angina (JCS2008) (JCS Joint Working Group. Circ J. 2010;74: ) 1) Total or subtotal coronary artery occlusion (>90% stenosis) during the provocation test accompanied by chest pain and/or ischemic ECG changes. and/or 2) An angina attack at rest or on effort accompanied by a transient ST segment elevation or depression or a negative U wave at least 2 related leads of ECG.

8 Definition of spasm type Diffuse-type Focal-type

9 Definition of spasm type Diffuse-type Focal-type + Mixed-type

10 Endpoints Primary Major adverse cardiac events (MACE) Cardiac death, non-fatal MI, unstable angina, heart failure, appropriate implantable cardioverter defibrillator (ICD) shocks Secondary All-cause death

11 Results

12 Patient flow diagram 1,528 patients were assessed for eligibility 99 patients were excluded because they did not meet the inclusion criteria Spontaneous attack n =185 Provocation test n=1,122 Spontaneous attack and provocation test n=122 1,244 VSA patients were included in the analysis

13 Provocation methods ACh + Erg 2% Others 1% Ergonovine (Erg) 40% Acetylcholine (ACh) 57%

14 (%) 80 Spasm-positive artery (n=1,184) % 59% % 32% % LAD LCx RCA LMT Multivessel

15 Arrhythmic complications Provocation tests (n=1,244) Spontaneous attack (n=1,244) PVC, n (%) 13 (1) 12 (1) VT/VF, n (%) 40 (3) 38 (3) AV block, n (%) 8 (1) 11 (1) Bradycardia/sinus pause, n (%) 28 (2) 23 (2) OHCA, n (%) - 32 (3) Overall, n (%) 85 (7) 87 (7) AV, atrioventricular; OHCA, out-of-hospital cardiac arrest; PVC, premature ventricular contraction; VF, ventricular fibrillation; VT, ventricular tachycardia.

16 Arrhythmic complications ACh (n=713) Erg (n=497) P value PVC, n (%) 5 (1) 8 (2) 0.13 VT/VF, n (%) 35 (5) 4 (1) <0.001 AV block, n (%) 3 (0.4) 3 (1) 0.48 Bradycardia/sinus pause, n (%) 26 (4) 2 (0.4) <0.001 Overall, n (%) 66 (9) 16 (3) <0.001 ACh, acetylcholine; AV, atrioventricular; Erg, ergonovine; PVC, premature ventricular contraction; VF, ventricular fibrillation; VT, ventricular tachycardia.

17 Demographic characteristics With prov-vt/vf (n=40) Without prov-vt/vf (n=1,204) P value Age, median (IQR), y 64 (59, 68) 66 (58, 73) 0.15 Female, n (%) 16 (40) 290 (24) Coronary risk factor, n (%) Hypertension 19 (48) 556 (46) 0.87 Dyslipidemia 22 (55) 559 (46) 0.29 Diabetes mellitus 9 (23) 203 (17) 0.35 Smoking 21 (53) 712 (59) 0.40 Previous MI, n (%) 4 (10) 80 (7) 0.28 Arrhythmia during attack, n (%) VT/VF 3 (8) 35 (3) 0.12 OHCA 2 (5) 30 (2) 0.28 IQR, interquartile range; MI, myocardial infarction; OHCA, out-of-hospital cardiac arrest; VF, ventricular fibrillation; VT, ventricular tachycardia.

18 Angiographic findings With prov-vt/vf (n=40) Without prov-vt/vf (n=1,204) P value Organic stenosis >50%, n (%) 4 (10) 176 (15) 0.41 Spasm-positive artery, n (%) LAD 18 (49) 648 (56) 0.34 diffuse/focal 11 (69)/5 (31) 364 (60)/248 (41) 0.46 LCx 13 (35) 304 (27) 0.24 diffuse/focal 10 (77)/3 (23) 190 (68)/90 (32) 0.36 RCA 28 (76) 665 (58) diffuse/focal 22 (81)/5 (19) 337 (55)/273 (45) Multivessel 18 (49) 356 (31) diffuse/focal/mixed 11 (64)/3 (18)/3 (18) 203 (59)/68 (20)/71 (21) 0.91 LAD, left anterior descending artery; LCx, left circumflex coronary artery; RCA, right coronary artery; VF, ventricular fibrillation; VT, ventricular tachycardia.

19 Correlated factors for prov-vt/vf Adjusted OR 95% CI P value Model 1 Female VT/VF during attack Diffuse RCA spasm Multivessel spasm Model 2 Female VT/VF during attack ACh Multivessel spasm ACh, acetylcholine; CI, confidence interval; OR, odds ratio; RCA, right coronary artery; VF, ventricular fibrillation; VT, ventricular tachycardia.

20 Medical treatments With prov-vt/vf (n=40) Without prov-vt/vf (n=1,204) P value Ca channel blockers, n (%) 38 (95) 1,135 (94) 0.60 Nitrates, n (%) 20 (50) 565 (47) 0.70 Antiplatelets, n (%) 25 (63) 554 (46) 0.40 Statins, n (%) 16 (40) 401 (33) 0.38 ACEI/ARBs, n (%) 11 (28) 291 (24) 0.63 Beta-blockers, n (%) 3 (8) 56 (5) 0.29 ACEI, angiotensin-converting enzime inhibitor; ARB, angiotensin receptor blocker; Ca, calcium; VF, ventricular fibrillation; VT, ventricular tachycardia.

21 Clinical outcomes With prov-vt/vf (n=40) Median follow-up: 32 months Without prov-vt/vf (n=1,204) P value MACE, n (%) 2 (5) 67 (6) 0.62 Cardiac death 0 (0) 4 (0.3) 0.88 Nonfatal MI 0 (0) 7 (1) 0.80 Unstable angina 2 (5) 53 (4) 0.54 Heart failure 0 (0) 3 (0.2) 0.91 ICD shock 0 (0) 2 (0.2) 0.94 All-cause death, n (%) 0 (0) 16 (1) 0.59 ICD, implantable cardioberter defibrillator; MACE, major adverse cardiac events; MI, myocardial infarction; VF, ventricular fibrillation; VT, ventricular tachycardia.

22 MACE-free survival (%) The Japanese Coronary Spasm Association Kaplan-Meier curve for MACE 100 Log-rank test: P= % 90 92% With prov-vt/vf (n=40) Without prov-vt/vf (n=1,204) Follow-up (months)

23 Correlated factors for MACE Adjusted HR 95% CI P value Multivessel spasm Type of spasm focal single vessel (ref) diffuse single vessel focal multivessel diffuse multivessel mixed multivessel Organic stenosis >50% Prov-related VT/VF Prov-related brady-arrhythmia Each variable were adjusted for age, sex, smoking, previous MI and OHCA in multivariable Cox model. CI, confidence interval; HR, hazard ratio; Prov, provocation; Ref, reference; VF, ventricular fibrillation; VT, ventricular tachycardia.

24 Summary 1) The incidence of arrhythmic complications during spasm provocation tests was comparable to that during spontaneous attack. 2) On multivariable analysis, female, use of ACh and diffuse RCA spasm were significantly correlated with provocation-related VT/VF.

25 Summary 3) The arrhythmic complications during provocation tests were not correlated with patient prognosis. 4) Multivariable analysis demonstrated that mixed-type multivessel spasm and organic coronary stenosis had a significant correlation with MACE.

26 Conclusions These findings may provide useful information for the prediction of arrhythmic complications during the spasm provocation tests and for the management of VSA patients.

27 Acknowledgement List of participating hospitals Teine Keijinkai Hospital, Hironori Murakami, MD. Hokkaido Cancer Center, Takashi Takenaka, MD. Sapporo Medical University, Kazuaki Shimamoto, MD. Asahikawa City Hospital, Kunihiko Hirasawa, MD. Hirosaki University, Ken Okumura, MD. Iwate Medical University, Motoyuki Nakamura, MD. Akita Medical Center, Tadaya Sato, MD. Akita University, Hiroshi Ito, MD. Yamagata University, Isao Kubota, MD. Yamagata Prefectural Central Hospital, Toshikazu Gotoh, MD. Tohoku University, Hiroaki Shimokawa, MD. Fukushima Medical University, Yasuchika Takeishi, MD. Dokkyo Medical University, Toshio Nishikimi, MD. Saitama Medical Center Jichi Medical University, Shinichi Momomura, MD. Kameda Medical Center, Makoto Suzuki, MD. Chiba Tokushukai Hospital, Osamu Ueda, MD. Jikei University, Michihiro Yoshimura, MD. Nihon University, Satoshi Saito, MD. Nihon University, Atsushi Hirayama, MD. Sakakibara Memorial Hospital, Tetsuya Sumiyoshi, MD. Keio University, Satoshi Ogawa, MD. Kyorin University, Hideaki Yoshino, MD. Nippon Medical School Hospital, Naoki Sato, MD. Tokai University Hachioji Hospital, Takahiko Kiyooka, MD. Tokai University, Yuji Ikari, MD. Yokohama City University Medical Center, Kazuo Kimura, MD. Showa University Fujigaoka Hospital, Youichi Takeyama, MD. Shizuoka General Hospital, Hirofumi Kambara, MD. Yamanashi University, Kiyotaka Kugiyama, MD. Shinsyu University, Yuichi Ikeda, MD. Niigata University, Yoshifusa Aizawa, MD. Shibata Hospital - Niigata Prefectural Hospital, Yasuhiko Tanabe, MD. Gifu University, Shinya Minatoguchi, MD. Toyama University, Inoue Hiroshi, MD. Nanto Family and Community Medical Center, Kunihisa Miwa, MD. Kanazawa University, Masakazu Yamagishi, MD. Shiga University of Medical Science, Minoru Horie, MD. Mie University, Masaaki Ito, MD. National Cardiovascular Center, Masafumi Kitakaze, MD. National Cardiovascular Center, Hiroshi Nonogi, MD. Osaka University, Yasuhiko Sakata, MD. Osaka City General Hospital, Akira Itoh, MD. Kinki University, Syunichi Miyazaki, MD. Nara Medical University, Tadahiko Saito, MD. Kinkidaigaku Igakubu Nara Hospital, Manabu Shiroya, MD. Wakayama Medical University, Takafumi Akasaka, MD. Saiseikai Nakatsu Hospital, Seinosuke Kawashima, MD. Kobe University, Kenichi Hirata, MD. Hiroshima University, Yasuki Kihara, MD. Hiroshima City Hospital, Ichiro Inoue, MD. Yamaguchi University, Masunori Matsuzaki, MD. Ehime University, Jitsuo Higaki, MD. Ehime Prefectural Niihama Hospital, Syozo Sueda, MD. Tokushima Red Cross Hospital, Yoshikazu Hiasa, MD. Kyushu Kousei Nenkin Hospital, Masahiro Mouri, MD. Omuta tenryo Hospital, Kooshi Matsuyama, MD. Kokura kinen Hospital, Hiroyasu Yokoi, MD. Fukuoka University Chikushi Hospital, Hidenori Urata, MD. Iizuka Hospital, Akira Yamada, MD. Shinbeppu Hospital, Natsuki Nakamura, MD. Nagasaki University, Koide Yuji, MD. Saga University, Koichi Node, MD. Kumamoto University, Hisao Ogawa, MD. Kumamoto Aging Research Institute, Hirofumi Yasue, MD. Saiseikai Kumamoto Hospital, Koichi Nakao, MD. Japanese Red Cross Kumamoto Hospital, Yasuhiro Ogata, MD. Kumamoto Medical Center, Kazuteru Fujimoto, MD. Kagoshima University, Cyuwa Tei, MD. Kagoshima Medical Center, Kazuhiko Nakamura, MD. Ryukyu University, Mitsuo Shimabukuro, MD. Sources of funding This study was supported by the Japan Heart Foundation.