非ST上昇型急性冠症候群におけるCK-MBのピーク値と30日ないし6カ月の死亡率の関係

出典
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1: Association between minor elevations of creatine kinase-MB level and mortality in patients with acute coronary syndromes without ST-segment elevation. PURSUIT Steering Committee. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy.
著者: J H Alexander, R A Sparapani, K W Mahaffey, J W Deckers, L K Newby, E M Ohman, R Corbalán, S L Chierchia, J B Boland, M L Simoons, R M Califf, E J Topol, R A Harrington
雑誌名: JAMA. 2000 Jan 19;283(3):347-53.
Abstract/Text: CONTEXT: Controversy surrounds the diagnostic and prognostic importance of slightly elevated cardiac markers in patients with acute coronary syndromes without ST-segment elevation.
OBJECTIVES: To investigate the relationship between peak creatine kinase (CK)-MB level and outcome and to determine whether a threshold CK-MB level exists below which risk is not increased.
DESIGN AND SETTING: Retrospective observational analysis of data from the international Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, conducted from November 1995 to January 1997.
PATIENTS: A total of 8250 patients with acute coronary syndromes without ST-segment elevation who had at least 1 CK-MB sample collected during their index hospitalization.
MAIN OUTCOME MEASURE: Mortality at 30 days and 6 months, was assessed by category of index-hospitalization peak CK-MB level (0-1, >1-2, >2-3, >3-5, >5-10, or >10 times the upper limit of normal). Multivariable logistic regression was used to determine the independent prognostic significance of peak CK-MB level after adjustment for baseline predictors of 30-day and 6-month mortality.
RESULTS: Mortality at 30 days and 6 months increased from 1.8% and 4.0%, respectively, in patients with normal peak CK-MB levels, to 3.3% and 6.2 % at peak CK-MB levels 1 to 2 times normal, to 5.1% and 7.5% at peak CK-MB levels 3 to 5 times normal, and to 8.3% and 11.0% at peak CK-MB levels greater than 10 times normal. Log-transformed peak CK-MB levels were predictive of adjusted 30-day and 6-month mortality (P<.001 for both).
CONCLUSIONS: Our data show that elevation of CK-MB level is strongly related to mortality in patients with acute coronary syndromes without ST-segment elevation, and that the increased risk begins with CK-MB levels just above normal. In the appropriate clinical context, even minor CK-MB elevations should be considered indicative of myocardial infarction.
JAMA. 2000 Jan 19;283(3):347-53.

不安定狭心症で入院した患者の冠動脈造影所見

出典
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1: 著者提供

Braunwaldの不安定狭心症の分類

2000年に改定された不安定狭心症の分類
出典
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1: A classification of unstable angina revisited.
著者: C W Hamm, E Braunwald
雑誌名: Circulation. 2000 Jul 4;102(1):118-22.
Abstract/Text: Unstable angina is a critical phase of coronary heart disease with widely variable symptoms and prognosis. A decade ago, a classification of unstable angina based on clinical symptoms was introduced. This system was then validated by prospective clinical studies to correlate with the prognosis and was linked to angiographic and histological findings. It has been used to categorize patients in many large clinical trials. In recent years, the pathophysiological roles of platelet activation and inflammation in unstable angina have been elucidated. Subsequently, improved markers of myocardial injury, acute-phase proteins, and hemostatic markers that may be associated with clinical outcomes have been identified. Particularly, cardiac-specific troponin T and troponin I have been shown to represent the best predictors of early risk in patients with angina at rest. Accordingly, it is suggested that the original classification be extended by subclassifying one large group of unstable angina patients, ie, those with angina at rest within the past 48 hours (class IIIB), into troponin-positive (T(pos)) and troponin-negative (T(neg)) patients. The 30-days risk for death and myocardial infarction is considered to be up to 20% in class IIIB-T(pos) but <2% in class IIIB-T(neg) patients. Initial results suggest that troponins may function as surrogate markers for thrombus formation and can effectively guide therapy with glycoprotein IIb/IIIa antagonists or low-molecular-weight heparins. These observations provide additional impetus for adding the measurement of these markers to the clinical classification and represent a novel concept of treating these high-risk patients.
Circulation. 2000 Jul 4;102(1):118-22.

急性冠症候群の分類

急性冠症候群という病態と、それに派生するさまざまな“結果”としての病名分類
出典
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1: 著者提供

急性冠症候群発症患者の発症前と発生直後の冠動脈造影

回旋枝に有意狭窄は存在しなかったが、急性冠症候群を発症し血栓を思わせる透亮像で冠動脈内腔が閉塞しかけている。
a：1年前の診断カテーテル
b：急性冠症候群発症時
出典
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1: 著者提供

一過性の心筋虚血を示唆する心電図所見

I,II, aVF, V2-5誘導で、down sloping　なST下降を認める。
出典
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1: 著者提供

T波の陰転

II, III, aVF, V4-6で、陰性T波を認める。虚血時間が比較的長く持続すると、新たなT波の陰転が残ることがある。もともと陰性T波を認める患者もいるので、疑わしい場合は以前の心電図との比較が必須である。
出典
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1: 著者提供

不安定狭心症の分類（Braunwald, 1989）

心筋逸脱酵素

一般的に心筋逸脱酵素の上昇のないものが不安定狭心症であるが、心電図だけでは心筋梗塞との鑑別は困難なことが少なくなく、かつ、梗塞後狭心症の可能性もあるため、心筋梗塞時に上昇する心筋逸脱酵素と病期の関係は理解しておく必要がある。

不安定狭心症患者の冠動脈造影

右冠動脈が急性冠症候群を発症し、高度狭窄を合併しているが完全には閉塞していない。
出典
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1: 著者提供

急性冠症候群（非ST 上昇型急性心筋梗塞，不安定狭心症）における短期リスク評価

診断後の侵襲治療の時期を決めるうえで、リスクの階層化を行うようにしている。

非ST上昇型急性冠症候群の薬物治療フローチャート

中等度リスクもしくは高リスクの症例は、最近では早期侵襲的治療の予後がよいとされている。
抗血小板薬は、現在は効果発現の早さから、クロピドグレルに加えプラスグレル20mgのローディング、3.75mgの維持投与も標準治療となっている。
抗凝固療法は、現在ではDOACの使用も一般的である。

冠動脈造影の適応、左室造影

観血的検査である冠動脈および左室造影は、急性冠症候群（ACS）患者のリスク判断に基づく。薬物で発作が抑えられない場合、心不全徴候がある場合、危険な不整脈がある場合、低心機能や左前下行枝病変や多枝疾患が疑われるとき、などが主な適応である。
＊リスク分類に関しては、短期リスク分類（[ID0701]） を参照。

短期リスク評価に基づいた治療戦略

リスク評価に基づき、早期侵襲治療か、早期保存療法かを大別する。

冠動脈狭窄率と心筋梗塞発生の関係

心筋梗塞で死亡した患者の責任血管の病理学的検討で、70％近くは有意狭窄を持たない病変に心筋梗塞を発症し、一般的に心筋梗塞発症直前にPCIの治療適応となる有意狭窄を認めるのは14％前後でしかない。
出典
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1: Coronary plaque disruption.
Circulation. 1995 Aug 1;92(3):657-71.

冠動脈プラークの発生、進行、臨床イベント発生までの過程を示す冠動脈切片の模式図

現在の冠動脈プラーク発生から、進行、臨床イベント発症にいたるメカニズムのレビュー
出典
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1: Current concepts of the pathogenesis of the acute coronary syndromes.
Circulation. 2001 Jul 17;104(3):365-72.
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2: Current concepts of the pathogenesis of the acute coronary syndromes.
Circulation. 2001 Jul 17;104(3):365-72.

病理および臨床所見でみた冠動脈硬化症の典型的な初期発生と進行

  1. 病理学的および臨床的所見に基づく、冠動脈プラークの典型的な初期から進行する課程　
アテロームは若年期から中年期にゆっくりと成長するが、この間臨床的には無症状である。やがて、複雑プラークのステージに入ると不安定粥腫となり、プラークの破綻を起こすことがある。破綻したプラークには血栓形成が続発し、血栓による閉塞もしくは高度狭窄を来せば急性冠症候群として発症し、内腔の高度狭窄を来さない場合には壁材血栓として内腔狭窄が一段と進む。
出典
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1: The pathogenesis of coronary artery disease and the acute coronary syndromes (1).
N Engl J Med. 1992 Jan 23;326(4):242-50. doi: 10.1056/NEJM199201233260406.

冠動脈プラークの発生、進行、臨床イベント発生までの過程を示す冠動脈切片の模式図

現在の冠動脈プラーク発生から、進行、臨床イベント発症にいたるメカニズムのレビュー
出典
imgimg
1: Current concepts of the pathogenesis of the acute coronary syndromes.
Circulation. 2001 Jul 17;104(3):365-72.
imgimg
2: Current concepts of the pathogenesis of the acute coronary syndromes.
Circulation. 2001 Jul 17;104(3):365-72.

プラーク破綻部位の病理所見

線維性皮膜の破綻とその部位を起点に血栓性閉塞をしている。
出典
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1: Pathology of the vulnerable plaque.
著者: Renu Virmani, Allen P Burke, Andrew Farb, Frank D Kolodgie
雑誌名: J Am Coll Cardiol. 2006 Apr 18;47(8 Suppl):C13-8. doi: 10.1016/j.jacc.2005.10.065.
Abstract/Text: The majority of patients with acute coronary syndromes (ACS) present with unstable angina, acute myocardial infarction, and sudden coronary death. The most common cause of coronary thrombosis is plaque rupture followed by plaque erosion, whereas calcified nodule is infrequent. If advances in coronary disease are to occur, it is important to recognize the precursor lesion of ACS. Of the three types of coronary thrombosis, a precursor lesion for acute rupture has been postulated. The non-thrombosed lesion that most resembles the acute plaque rupture is the thin cap fibroatheroma (TCFA), which is characterized by a necrotic core with an overlying fibrous cap measuring <65 microm, containing rare smooth muscle cells but numerous macrophages. Thin cap fibroatheromas are most frequently observed in patients dying with acute myocardial infarction and least common in plaque erosion. They are most frequently observed in proximal coronary arteries, followed by mid and distal major coronary arteries. Vessels demonstrating TCFA do not usually show severe narrowing but show positive remodeling. In TCFAs the necrotic core length is approximately 2 to 17 mm (mean 8 mm) and the underlying cross-sectional area narrowing in over 75% of cases is <75% (diameter stenosis <50%). The area of the necrotic core in at least 75% of cases is < or =3 mm2. These lesions have lesser degree of calcification than plaque ruptures. Thin cap fibroatheromas are common in patients with high total cholesterol (TC) and high TC/high-density lipoprotein cholesterol ratio, in women >50 years, and in those patients with elevated high levels of high sensitivity C-reactive protein. It has only recently been recognized that their identification in living patients might help reduce the incidence of sudden coronary death.
J Am Coll Cardiol. 2006 Apr 18;47(8 Suppl):C13-8. doi: 10.1016/j.jacc....

非ST上昇型急性冠症候群におけるCK-MBのピーク値と30日ないし6カ月の死亡率の関係

出典
imgimg
1: Association between minor elevations of creatine kinase-MB level and mortality in patients with acute coronary syndromes without ST-segment elevation. PURSUIT Steering Committee. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy.
著者: J H Alexander, R A Sparapani, K W Mahaffey, J W Deckers, L K Newby, E M Ohman, R Corbalán, S L Chierchia, J B Boland, M L Simoons, R M Califf, E J Topol, R A Harrington
雑誌名: JAMA. 2000 Jan 19;283(3):347-53.
Abstract/Text: CONTEXT: Controversy surrounds the diagnostic and prognostic importance of slightly elevated cardiac markers in patients with acute coronary syndromes without ST-segment elevation.
OBJECTIVES: To investigate the relationship between peak creatine kinase (CK)-MB level and outcome and to determine whether a threshold CK-MB level exists below which risk is not increased.
DESIGN AND SETTING: Retrospective observational analysis of data from the international Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, conducted from November 1995 to January 1997.
PATIENTS: A total of 8250 patients with acute coronary syndromes without ST-segment elevation who had at least 1 CK-MB sample collected during their index hospitalization.
MAIN OUTCOME MEASURE: Mortality at 30 days and 6 months, was assessed by category of index-hospitalization peak CK-MB level (0-1, >1-2, >2-3, >3-5, >5-10, or >10 times the upper limit of normal). Multivariable logistic regression was used to determine the independent prognostic significance of peak CK-MB level after adjustment for baseline predictors of 30-day and 6-month mortality.
RESULTS: Mortality at 30 days and 6 months increased from 1.8% and 4.0%, respectively, in patients with normal peak CK-MB levels, to 3.3% and 6.2 % at peak CK-MB levels 1 to 2 times normal, to 5.1% and 7.5% at peak CK-MB levels 3 to 5 times normal, and to 8.3% and 11.0% at peak CK-MB levels greater than 10 times normal. Log-transformed peak CK-MB levels were predictive of adjusted 30-day and 6-month mortality (P<.001 for both).
CONCLUSIONS: Our data show that elevation of CK-MB level is strongly related to mortality in patients with acute coronary syndromes without ST-segment elevation, and that the increased risk begins with CK-MB levels just above normal. In the appropriate clinical context, even minor CK-MB elevations should be considered indicative of myocardial infarction.
JAMA. 2000 Jan 19;283(3):347-53.

不安定狭心症で入院した患者の冠動脈造影所見

出典
img
1: 著者提供