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虚血性心不全

著者: 清野精彦(せいの よしひこ) 日本医科大学 名誉教授

監修: 代田浩之 順天堂大学大学院医学研究科循環器内科学

著者校正/監修レビュー済:2019/10/26
参考ガイドライン:
急性・慢性心不全診療ガイドライン 2017年改訂版
急性冠症候群診療ガイドライン 2018年度改訂版
2013 ESC guidelines on the management of stable coronary artery disease
2014 ESC guidelines for revascularization
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure
 
患者向け説明資料
薬価収載情報:2021年8月12日 ベリキューボ 錠(ベルイシグアト 可溶性グアニル酸シクラーゼ(sGC)刺激剤)

概要・推奨   

  1. 冠動脈疾患を合併した心不全の薬物療法(ACE阻害薬,ARB、β遮断薬,MRA)の推奨とエビデンスを表示。(表
  1. 高強度、低強度スタチン治療群、非スタチン治療群の順に、LDL-C値にかかわらず心血管イベント(全死亡・心不全による入院)が有意に低下する。
  1. 慢性虚血性心不全に対する冠動脈再開通療法 -薬物療法vs PCI vs CABG-を解説。
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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:
清野精彦(せいの よしひこ) : 特に申告事項無し[2021年]
監修:代田浩之 : 未申告[2021年]

改訂のポイント:
  1. 急性・慢性心不全診療ガイドラインに基づき薬物治療の推奨とエビデンスを引用表示した。
  1. 最新の論文に基づき薬物治療(スタチン強度)の重要性を加筆した。
  1. 最新の論文に基づき慢性虚血性心不全に対する冠動脈再開通療法 -薬物療法vs PCI vs CABG-の解説を更新した。
  1. 虚血性重症心不全に対する再生医療の成績のレビューを追記した。

病態・疫学・診察

疾患情報  
  1. 虚血性心不全としては、以下のように急性と慢性に識別して診療するが、ここでは慢性虚血性心不全について取り上げる。
 
急性虚血性心不全:
  1. 急性冠症候群( ST上昇型心筋梗塞 、 非ST上昇型心筋梗塞 の項を参照のこと)
 
 
  1. 急性心筋梗塞に伴うポンプ失調(acute myocardial infarction[AMI]with pump failure)
 
ST上昇型心筋梗塞におけるポンプ失調

 
  1. 二次性(動的)僧帽弁逆流(secondary :dynamic mitral regurgitation)
  1. 気絶心筋(stunned myocardium)
 
気絶心筋

閉塞冠動脈を再開通したにもかかわらず心室の壁運動障害が遷延して、回復まで数日を要する病態を気絶心筋という。急性心筋梗塞血行再建術のみならず冠動脈攣縮後、PCI後などにも観察される。その機序を図中に列記する。
 
参考文献:
Kloner RA, Przyklenk K, Patel B.:Altered myocardial states. The stunned and hibernating myocardium. Am J Med.1989 Jan 16;86(1A):14-22. Review. PMID:2644829

出典

img1:  著者提供
 
 
 
  1. 再灌流障害(reperfusion injury)
 
慢性虚血性心不全:
  1. 心室リモデリングを伴った陳旧性心筋梗塞(previous myocardial infarction with remodeling)
 
急性心筋梗塞後の心室リモデリング

梗塞サイズ(大ほど著明)、左室負荷(急性期高血圧、慢性的容量負荷で著明)
梗塞責任動脈の開存性(閉塞、高度狭窄で大)、梗塞部位(前壁、心尖部で著明)
a:初回梗塞
b:梗塞部位のexpansion(数時間から数日)
c:全体的なモデリング(数日から数カ月)

 
  1. 冬眠心筋(myocardial hibernation)
 
冬眠心筋

安定狭心症などで心筋梗塞がないにもかかわらず慢性的な虚血により収縮障害を生じている病態。その機序について図中に列記する。
 
参考文献:
  1. Rahimtoola SH.:Coronary bypass surgery for chronic angina--1981. A perspective. Circulation. 1982 Feb;65(2):225-41. Review. PMID:7032746

出典

img1:  著者提供
 
 
 
  1. いわゆる虚血性心筋症(so called ischemic cardiomyopathy)
  1. 収縮能が保持された心不全(heart failure with preserved ejection fraction:HFpEF)( 心不全 拡張能障害 の項を参照のこと)
問診・診察のポイント  
慢性虚血性心不全について:
  1. 冠動脈疾患の危険因子をチェックする(例:高血圧、脂質異常症、喫煙、糖尿病、メタボリックシンドローム、家族歴など)。慢性腎臓病(CKD)も冠動脈疾患進行の危険因子なので留意したい。

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文献 

著者: John J V McMurray, Stamatis Adamopoulos, Stefan D Anker, Angelo Auricchio, Michael Böhm, Kenneth Dickstein, Volkmar Falk, Gerasimos Filippatos, Cândida Fonseca, Miguel Angel Gomez-Sanchez, Tiny Jaarsma, Lars Køber, Gregory Y H Lip, Aldo Pietro Maggioni, Alexander Parkhomenko, Burkert M Pieske, Bogdan A Popescu, Per K Rønnevik, Frans H Rutten, Juerg Schwitter, Petar Seferovic, Janina Stepinska, Pedro T Trindade, Adriaan A Voors, Faiez Zannad, Andreas Zeiher, Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology, Jeroen J Bax, Helmut Baumgartner, Claudio Ceconi, Veronica Dean, Christi Deaton, Robert Fagard, Christian Funck-Brentano, David Hasdai, Arno Hoes, Paulus Kirchhof, Juhani Knuuti, Philippe Kolh, Theresa McDonagh, Cyril Moulin, Bogdan A Popescu, Zeljko Reiner, Udo Sechtem, Per Anton Sirnes, Michal Tendera, Adam Torbicki, Alec Vahanian, Stephan Windecker, Theresa McDonagh, Udo Sechtem, Luis Almenar Bonet, Panayiotis Avraamides, Hisham A Ben Lamin, Michele Brignole, Antonio Coca, Peter Cowburn, Henry Dargie, Perry Elliott, Frank Arnold Flachskampf, Guido Francesco Guida, Suzanna Hardman, Bernard Iung, Bela Merkely, Christian Mueller, John N Nanas, Olav Wendelboe Nielsen, Stein Orn, John T Parissis, Piotr Ponikowski, ESC Committee for Practice Guidelines
雑誌名: Eur J Heart Fail. 2012 Aug;14(8):803-69. doi: 10.1093/eurjhf/hfs105.
Abstract/Text
PMID 22828712  Eur J Heart Fail. 2012 Aug;14(8):803-69. doi: 10.1093/e・・・
著者: Takuya Oikawa, Yasuhiko Sakata, Kotaro Nochioka, Masanobu Miura, Kanako Tsuji, Takeo Onose, Ruri Abe, Shintaro Kasahara, Masayuki Sato, Takashi Shiroto, Jun Takahashi, Satoshi Miyata, Hiroaki Shimokawa, CHART‐2 invesigators
雑誌名: J Am Heart Assoc. 2018 Mar 14;7(6). doi: 10.1161/JAHA.117.007524. Epub 2018 Mar 14.
Abstract/Text BACKGROUND: The beneficial prognostic impact of statins has been established in patients with ischemic heart disease but not in those with heart failure (HF). In addition, it is still unclear whether patients benefit from statins regardless of low-density lipoprotein cholesterol levels.
METHODS AND RESULTS: We examined 2444 consecutive stage C or D HF patients with ischemic heart disease registered in CHART-2 (Chronic Heart Failure Registry and Analysis in the Tohoku District 2), a multicenter, prospective, observational cohort study in Japan. Patients were divided into 3 groups according to the Japanese standard doses of statins and statin-intensity categories defined by the 2013 American College of Cardiology and American Heart Association guidelines: higher (moderate-high)-intensity (n=868), lower (low)-intensity (n=526), and no statin (n=1050). The median follow-up period was 6.4 years (13929 person-years). Analysis with the inverse probability of treatment weighted using a propensity score for multiple treatment revealed that both the higher-intesity group (hazard ratio [HR]: 0.68; P<0.001) and the lower-intensity group (HR: 0.82; P<0.001) had significantly lower incidence of the primary end point-a composite of all-cause death and HF admission-compared with the no statin group. The higher-intensity statin group had significantly lower incidence of the primary end point (HR: 0.82; P<0.001), all-cause death (HR: 0.83; P<0.001), and HF admission (HR: 0.78; P<0.001) than the lower-intensity statin group. Moreover, the use of statins, either higher- or lower-intensity, was associated with reduced incidence of the primary end point, regardless of low-density lipoprotein cholesterol levels.
CONCLUSIONS: These results suggest that statin use, particularly the use of higher-intensity statins, has a beneficial prognostic impact in HF patients with ischemic heart disease, regardless of low-density lipoprotein cholesterol levels.
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00418041.

© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
PMID 29540427  J Am Heart Assoc. 2018 Mar 14;7(6). doi: 10.1161/JAHA.1・・・
著者: Mihai Gheorghiade, George Sopko, Leonardo De Luca, Eric J Velazquez, John D Parker, Philip F Binkley, Zygmunt Sadowski, Krzysztof S Golba, David L Prior, Jean L Rouleau, Robert O Bonow
雑誌名: Circulation. 2006 Sep 12;114(11):1202-13. doi: 10.1161/CIRCULATIONAHA.106.623199.
Abstract/Text
PMID 16966596  Circulation. 2006 Sep 12;114(11):1202-13. doi: 10.1161/・・・
著者: Eric J Velazquez, Kerry L Lee, Robert H Jones, Hussein R Al-Khalidi, James A Hill, Julio A Panza, Robert E Michler, Robert O Bonow, Torsten Doenst, Mark C Petrie, Jae K Oh, Lilin She, Vanessa L Moore, Patrice Desvigne-Nickens, George Sopko, Jean L Rouleau, STICHES Investigators
雑誌名: N Engl J Med. 2016 Apr 21;374(16):1511-20. doi: 10.1056/NEJMoa1602001. Epub 2016 Apr 3.
Abstract/Text BACKGROUND: The survival benefit of a strategy of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, as compared with medical therapy alone, in patients with coronary artery disease, heart failure, and severe left ventricular systolic dysfunction remains unclear.
METHODS: From July 2002 to May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to undergo CABG plus medical therapy (CABG group, 610 patients) or medical therapy alone (medical-therapy group, 602 patients). The primary outcome was death from any cause. Major secondary outcomes included death from cardiovascular causes and death from any cause or hospitalization for cardiovascular causes. The median duration of follow-up, including the current extended-follow-up study, was 9.8 years.
RESULTS: A primary outcome event occurred in 359 patients (58.9%) in the CABG group and in 398 patients (66.1%) in the medical-therapy group (hazard ratio with CABG vs. medical therapy, 0.84; 95% confidence interval [CI], 0.73 to 0.97; P=0.02 by log-rank test). A total of 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical-therapy group died from cardiovascular causes (hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006 by log-rank test). Death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and in 524 patients (87.0%) in the medical-therapy group (hazard ratio, 0.72; 95% CI, 0.64 to 0.82; P<0.001 by log-rank test).
CONCLUSIONS: In a cohort of patients with ischemic cardiomyopathy, the rates of death from any cause, death from cardiovascular causes, and death from any cause or hospitalization for cardiovascular causes were significantly lower over 10 years among patients who underwent CABG in addition to receiving medical therapy than among those who received medical therapy alone. (Funded by the National Institutes of Health; STICH [and STICHES] ClinicalTrials.gov number, NCT00023595.).

PMID 27040723  N Engl J Med. 2016 Apr 21;374(16):1511-20. doi: 10.1056・・・
著者: Georg Wolff, Dimitrios Dimitroulis, Felicita Andreotti, Michalina Kołodziejczak, Christian Jung, Pietro Scicchitano, Fiorella Devito, Annapaola Zito, Michele Occhipinti, Battistina Castiglioni, Giuseppe Calveri, Francesco Maisano, Marco M Ciccone, Stefano De Servi, Eliano P Navarese
雑誌名: Circ Heart Fail. 2017 Jan;10(1). doi: 10.1161/CIRCHEARTFAILURE.116.003255.
Abstract/Text BACKGROUND: Heart failure with reduced ejection fraction caused by ischemic heart disease is associated with increased morbidity and mortality. It remains unclear whether revascularization by either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) carries benefits or risks in this group of stable patients compared with medical treatment.
METHODS AND RESULTS: We performed a meta-analysis of available studies comparing different methods of revascularization (PCI or CABG) against each other or medical treatment in patients with coronary artery disease and left ventricular ejection fraction ≤40%. The primary outcome was all-cause mortality; myocardial infarction, revascularization, and stroke were also analyzed. Twenty-one studies involving a total of 16 191 patients were included. Compared with medical treatment, there was a significant mortality reduction with CABG (hazard ratio, 0.66; 95% confidence interval, 0.61-0.72; P<0.001) and PCI (hazard ratio, 0.73; 95% confidence interval, 0.62-0.85; P<0.001). When compared with PCI, CABG still showed a survival benefit (hazard ratio, 0.82; 95% confidence interval, 0.75-0.90; P<0.001).
CONCLUSIONS: The present meta-analysis indicates that revascularization strategies are superior to medical treatment in improving survival in patients with ischemic heart disease and reduced ejection fraction. Between the 2 revascularization strategies, CABG seems more favorable compared with PCI in this particular clinical setting.

© 2017 American Heart Association, Inc.
PMID 28087687  Circ Heart Fail. 2017 Jan;10(1). doi: 10.1161/CIRCHEART・・・
著者: Alexander Iribarne, Anthony W DiScipio, Bruce J Leavitt, Yvon R Baribeau, Jock N McCullough, Paul W Weldner, Yi-Ling Huang, Michael P Robich, Robert A Clough, Gerald L Sardella, Elaine M Olmstead, David J Malenka, Northern New England Cardiovascular Disease Study Group
雑誌名: J Thorac Cardiovasc Surg. 2018 Oct;156(4):1410-1421.e2. doi: 10.1016/j.jtcvs.2018.04.121. Epub 2018 Jun 1.
Abstract/Text OBJECTIVE: There are no prospective randomized trial data to guide decisions on optimal revascularization strategies for patients with multivessel coronary artery disease and reduced ejection fraction. In this analysis, we describe the comparative effectiveness of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in this patient population.
METHODS: A multicenter, retrospective analysis of all CABG (n = 18,292) and PCIs (n = 55,438) performed from 2004 to 2014 among 7 medical centers reporting to the Northern New England Cardiovascular Disease Study Group. After applying inclusion and exclusion criteria from the Surgical Treatment for Ischemic Heart Failure trial, there were 955 CABG and 718 PCI patients with an ejection fraction ≤ 35% and 2- or 3-vessel disease. Inverse probability weighting was used for risk adjustment. The primary end point was all-cause mortality. Secondary end points included rates of 30-day mortality, stroke, acute kidney injury, and incidence of repeat revascularization.
RESULTS: The median duration of follow-up was 4.3 years (range, 1.59-6.71 years). CABG was associated with improved long-term survival compared with PCI after risk adjustment (hazard ratio, 0.59; 95% confidence interval, 0.50-0.71; P < .01). Although CABG and PCI had similar 30-day mortality rates (P = .14), CABG was associated with a higher frequency of stroke (P < .001) and acute kidney injury (P < .001), whereas PCI was associated with a higher incidence of repeat revascularization (P < .001).
CONCLUSIONS: Among patients with reduced ejection fraction and multivessel disease, CABG was associated with improved long-term survival compared with PCI. CABG should be strongly considered in patients with ischemic cardiomyopathy and multivessel coronary disease.

Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
PMID 29961592  J Thorac Cardiovasc Surg. 2018 Oct;156(4):1410-1421.e2.・・・
著者: Waddah Maskoun, Marwan Saad, Amjad Abualsuod, Ramez Nairooz, John M Miller
雑誌名: Int J Cardiol. 2018 Sep 15;267:107-113. doi: 10.1016/j.ijcard.2018.03.127. Epub 2018 Apr 8.
Abstract/Text BACKGROUND: Current ventricular tachycardia (VT) management in patients with ischemic cardiomyopathy (ICM) includes optimal medical therapy, ICDs device therapy, and antiarrhythmic medications. Data about outcomes of catheter ablation (CA) in these patients is scarce. We aimed to perform a meta-analysis of RCTs to compare outcomes of CA vs conventional management of VT in ICM patients who had ICD.
METHODS: A systematic review and meta-analysis of published RCTs between January 1970 and December 2016 were performed. Random effects DerSimonian-Laird risk ratios (RR) were calculated. Sensitivity analyses using fixed-effects summary odds ratios (OR) were performed using Peto model. Outcomes of interest were: all-cause mortality (ACM), cardiovascular death (CVD), CV disease-related hospitalization, VT storms, and ICD shocks.
RESULTS: 4 RCTs were identified (521 patients (261 had CA), mean age: 66.4 ± 1.7 years, 91.5% male, mean follow-up: 19 months). No difference observed between VT ablation and conventional management regarding ACM (RR 0.94, 95% CI, 0.66-1.32, p = 0.70) or CVD (RR 0.82, 95% CI, 0.52-1.29, p = 0.39). VT ablation was associated with less CV disease-related hospitalization (RR 0.72, 95% CI, 0.54-0.96, p = 0.02), VT storms (RR 0.71, 95% CI, 0.52-0.97, p = 0.03), and trend towards reducing ICD shocks (RR 0.59, 95% CI, 0.34-1.05, p = 0.07). In sensitivity analysis using fixed-effects OR, CA was associated with significant reduction in ICD shocks.
CONCLUSION: In patients with ICM, VT ablation reduced CV disease-related hospitalization, VT storms, and ICD shocks when compared to conventional management with no mortality benefit over a relatively short mean follow-up period.

Copyright © 2018 Elsevier B.V. All rights reserved.
PMID 29655948  Int J Cardiol. 2018 Sep 15;267:107-113. doi: 10.1016/j.・・・
著者: Jozef Bartunek, Andre Terzic, Beth A Davison, Gerasimos S Filippatos, Slavica Radovanovic, Branko Beleslin, Bela Merkely, Piotr Musialek, Wojciech Wojakowski, Peter Andreka, Ivan G Horvath, Amos Katz, Dariouch Dolatabadi, Badih El Nakadi, Aleksandra Arandjelovic, Istvan Edes, Petar M Seferovic, Slobodan Obradovic, Marc Vanderheyden, Nikola Jagic, Ivo Petrov, Shaul Atar, Majdi Halabi, Valeri L Gelev, Michael K Shochat, Jaroslaw D Kasprzak, Ricardo Sanz-Ruiz, Guy R Heyndrickx, Noémi Nyolczas, Victor Legrand, Antoine Guédès, Alex Heyse, Tiziano Moccetti, Francisco Fernandez-Aviles, Pilar Jimenez-Quevedo, Antoni Bayes-Genis, Jose Maria Hernandez-Garcia, Flavio Ribichini, Marcin Gruchala, Scott A Waldman, John R Teerlink, Bernard J Gersh, Thomas J Povsic, Timothy D Henry, Marco Metra, Roger J Hajjar, Michal Tendera, Atta Behfar, Bertrand Alexandre, Aymeric Seron, Wendy Gattis Stough, Warren Sherman, Gad Cotter, William Wijns, CHART Program
雑誌名: Eur Heart J. 2017 Mar 1;38(9):648-660. doi: 10.1093/eurheartj/ehw543.
Abstract/Text Aims: Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort.
Methods and results: This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein-Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann-Whitney estimator 0.54, 95% confidence interval [CI] 0.47-0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200-370 mL (60% of patients) (Mann-Whitney estimator 0.61, 95% CI 0.52-0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death.
Conclusion: The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.

© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.
PMID 28025189  Eur Heart J. 2017 Mar 1;38(9):648-660. doi: 10.1093/eur・・・

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