StatPearls Troponin
診斷心臟緊急情況是緊急救治人員最重要的任務之一。必須快速準確地縮小胸痛的廣泛鑑別診斷範圍，以執行患者所需的挽救生命的治療。 [1] 除了病史和體格檢查外，還使用幾種重要的診斷工具來區分胸痛的不同原因。 [2] 肌鈣蛋白的測量已成為心臟檢查和診斷的重要組成部分。
Introduction
Introduction
Diagnosing cardiac emergencies is one of the most crucial tasks delegated to the emergency provider. The broad differential diagnosis of chest pain must be narrowed down quickly and accurately to perform the life-saving treatments patients require.[1] Along with the history and physical examination, several important diagnostic tools are used to differentiate the different causes of chest pain.[2] One tool that has become an essential component of cardiac workups and diagnosis is the measurement of troponins.[3]
自 1995 年批准第一個心肌肌鈣蛋白 T (cTnT) 測定以來，心肌肌鈣蛋白已可用於臨床。 [4] 從那時起，人們已經清楚，心臟特異性的增強和特別是敏感性的提高可以使心血管異常的診斷更頻繁、更準確，特別是在實施高靈敏度心肌肌鈣蛋白檢測後。 [5]
Cardiac troponins have been available for clinical use since 1995, when the first cardiac troponin T (cTnT) assay was approved.[4] Since then, it has become clear that enhanced cardiac specificity and particularly improved sensitivity lead to more frequent and more accurate diagnoses of cardiovascular abnormalities, especially with the implementation of high-sensitivity cardiac troponins assays.[5]
病理生理學
當為心肌供氧的冠狀血管中的血流受阻時，就會發生心肌梗死。 [16] 這會導致氧氣供應無法滿足肌細胞的需氧量的不匹配，從而導致壞死和細胞死亡。 [17] 在此過程中，細胞膜破裂，導致細胞內內容物溢出到細胞外空間，最終進入血液。 [18] 如果這些細胞內容物（包括肌鈣蛋白）溢出足夠多，則可以在循環血液中檢測到它們。
Pathophysiology
Myocardial infarction occurs when blood flow is blocked in the coronary vessels that supply the heart muscle with oxygen.[16] This causes a mismatch where the oxygen supply is not meeting the oxygen demand of the myocytes, leading to necrosis and cell death.[17] During this process, the cell membranes are ruptured, causing intracellular contents to spill into the extracellular space, eventually making their way into the bloodstream.[18] If these cellular contents, including troponins, are spilled in large enough quantities, they can be detected in the circulating blood.[16]
在健康個體的循環中，心肌細胞的定期更新中發現了基礎量的肌鈣蛋白。 [19] 當測量值大於正常範圍的第 99 個百分位數（比平均值高出約三個標準差）時，肌鈣蛋白表明存在病理生理性肌肉損傷。 [20] 根據心肌梗死的第四個通用定義，cTn 值高於第 99 個百分位數參考上限被定義為心肌損傷。 [15] 如果心肌肌鈣蛋白值上升、下降或上升和下降，則認為損傷是急性的。 [21]
A basal amount of troponin is found in the circulation of healthy individuals from the regular turnover of cardiac myocytes.[19] Troponin indicates pathophysiologic muscle damage when the measured value is greater than the 99th percentile of the normal range, about three standard deviations above the mean.[20] According to the Fourth Universal Definition of Myocardial Infarction, a cTn value above the 99th percentile upper reference limit is defined as myocardial injury.[15] The injury is considered acute if there is a rise, fall, or a rise and fall in cardiac troponins values.[21]
胸痛發作後兩到三個小時內，循環中的肌鈣蛋白水平通常開始升高。該水平將持續上升，直至達到峰值，通常在 12 至 48 小時之間。肌鈣蛋白水平將在接下來的四到十天內降至正常。[22] 肌鈣蛋白的這種預期上升和下降有助於區分心肌梗塞和肌鈣蛋白升高的其他原因。 [23] cTnI 和 cTnT 的實際半衰期都很短，在血漿中大約為兩個小時。然而，由於壞死心肌持續釋放肌鈣蛋白，表觀半衰期為24小時，cTnT稍長。 [24]
Troponin levels typically start to elevate in the circulation within two to three hours of the onset of chest pain. The levels will continue to rise until a peak is reached, generally between 12 and 48 hours. The troponin level will then fall to normal over the next four to ten days.[22] This expected rise and fall of the troponin can help distinguish a myocardial infarction from other causes of elevated troponins.[23] The actual half-life of both cTnI and cTnT is short – approximately two hours in plasma. However, because of the continued release of troponin from the necrotic myocardium, the apparent half-life is 24 hours, with cTnT slightly longer.[24]
心肌肌鈣蛋白 T (cTnT) 和肌鈣蛋白 I (cTnI) 具有與骨骼亞型不同的氨基酸序列，並由獨特的基因編碼。 [25] 與骨骼肌 TnI 相比，人 cTnI 在氨基末端多了 31 個氨基酸殘基，使其具有完全的心臟特異性。 [26] 僅鑑定出一種 cTnI 亞型。cTnI 在健康、再生或患病的人類或動物骨骼肌中不表達。 [27] cTnT 的編碼基因與編碼骨骼肌亞型的基因不同。11 個氨基酸的氨基末端殘基賦予該標記物獨特的心臟特異性。[24]
Cardiac troponin T (cTnT) and troponin I (cTnI) have amino acid sequences that differ from the skeletal isoforms and are encoded by unique genes.[25] Human cTnI has an additional 31 amino-acid residue on the amino-terminal end compared with skeletal muscle TnI, giving it complete cardiac specificity.[26] Only one isoform of cTnI has been identified. cTnI is not expressed in healthy, regenerating, or diseased human or animal skeletal muscle.[27] cTnT is encoded by a different gene than the one that encodes for skeletal muscle isoforms. An 11-amino acid amino-terminal residue gives this marker unique cardiac specificity.[24]
在人類中，cTnT 同工型表達已在肌營養不良症、多發性肌炎、皮肌炎和終末期腎病患者的骨骼肌標本中得到證實。 [28] 因此，必須謹慎選擇用於cTnT 測定的抗體對，這些抗體對不能檢測這些表達的亞型或在神經肌肉骨骼疾病中表達的免疫反應蛋白，這些疾病與商業cTnT 測定具有交叉反應性，因為可能會出現假陽性、非心臟cTnT 結果。 [29]
In humans, cTnT isoform expression has been demonstrated in skeletal muscle specimens obtained from patients with muscular dystrophy, polymyositis, dermatomyositis, and end-stage renal disease.[28] Thus care is necessary to choose antibody pairs for the cTnT assay that do not detect these expressed isoforms or the immunoreactive proteins expressed in neuromuscular skeletal diseases that show cross-reactivity to the commercial cTnT assays because false-positive, noncardiac, cTnT results can occur.[29]
結果、報告和重要發現
當前（第四版）MI 通用定義專家共識文件更新了 MI 的定義，以適應高敏心肌肌鈣蛋白 (hs-cTn) 使用的增加。檢測到 cTn 值高於第 99 個百分位數參考上限 (URL) 被定義為心肌損傷。 [95] 如果 cTn 值上升和/或下降，則認為損傷是急性損傷。[15]
Results, Reporting, and Critical Findings
The current (fourth) Universal Definition of MI Expert Consensus Document updates the definition of MI to accommodate the increased use of high-sensitivity cardiac troponin (hs-cTn). Detection of an elevated cTn value above the 99th percentile upper reference limit (URL) is defined as myocardial injury.[95] The injury is considered acute if there is a rise and/or fall of cTn values.[15]
第 1 型心肌梗塞
1 型 MI 的標準包括檢測到 cTn 的上升、下降或上升和下降，且至少有一個值高於第 99 個百分位數，並且至少具有以下一項：
Type 1 Myocardial Infarction
The criteria for type 1 MI includes the detection of a rise, fall, or rise and fall of cTn with at least one value above the 99th percentile and with at least one of the following:
急性心肌缺血的症狀
新的缺血性心電圖 (ECG) 變化
病理性 Q 波的發展
影像學證據顯示新的存活心肌喪失或新的局部室壁運動異常，其模式與缺血性病因一致
通過血管造影（包括冠狀動脈內成像或屍檢）識別冠狀動脈血栓
Symptoms of acute myocardial ischemia
New ischemic electrocardiographic (ECG) changes
Development of pathological Q waves
Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology
Identification of a coronary thrombus by angiography, including intracoronary imaging or by autopsy
2 型心肌梗塞
2 型MI 的標準包括檢測到cTn 的上升、下降或上升和下降，且至少有一個值高於第99 個百分位，並且有證據表明與冠狀動脈血栓形成無關的心肌氧供需之間存在不平衡，需要至少滿足以下一項條件：下列：
Type 2 Myocardial Infarction
The criteria for type 2 MI includes detection of a rise, fall, or rise and fall of cTn with at least one value above the 99th percentile and evidence of an imbalance between myocardial oxygen supply and demand unrelated to coronary thrombosis, requiring at least one of the following:
急性心肌缺血的症狀
新的缺血性心電圖變化
病理性 Q 波的發展
影像學證據顯示新的存活心肌喪失或新的局部室壁運動異常，其模式與缺血性病因一致
心臟手術性心肌損傷
Symptoms of acute myocardial ischemia
New ischemic ECG changes
Development of pathological Q waves
Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology
Cardiac Procedural Myocardial Injury
心臟手術性心肌損傷是任意定義的，即基線值正常（≤ URL 99%）的患者cTn 值增加（> 99% URL），或者當cTn 值高於99% 時，cTn 值增加> 基線值的20 % ，但它是穩定的或下降的。
Cardiac procedural myocardial injury is arbitrarily defined by increases in cTn values (>99th percentile URL) in patients with normal baseline values (≤99th percentile URL) or a rise of cTn values >20% of the baseline value when it is above the 99th percentile, but it is stable or falling.
冠狀動脈介入治療相關的心肌梗死
冠狀動脈介入相關的 MI 是通過基線值正常的患者中 cTn 值升高 > 99% URL 的 5 倍任意定義的。對於術前 cTn 升高且 cTn 水平穩定（≤20% 變化）或下降的患者，術後 cTn 必須升 >20%。但是，絕對後處理值仍必須至少是第 99 個百分位數 URL 的五倍。此外，還需要以下元素之一：
Coronary Intervention-related Myocardial Infarction
Coronary intervention-related MI is arbitrarily defined by the elevation of cTn values >5 times the 99th percentile URL in patients with normal baseline values. In patients with elevated pre-procedure cTn in whom the cTn levels are stable (≤20% variation) or falling, the post-procedure cTn must rise by >20%. However, the absolute post-procedural value must still be at least five times the 99th percentile URL. In addition, one of the following elements is required:
新的缺血性心電圖變化
新病理Q波的發展
血管造影結果與手術限流並發症一致，例如冠狀動脈夾層、主要心外膜動脈閉塞或側支閉塞或血栓、側支血流中斷或遠端栓塞
冠狀動脈搭橋術 (CABG) 相關的心肌梗塞
New ischemic ECG changes
Development of new pathological Q waves
Angiographic findings are consistent with a procedural flow-limiting complication such as coronary dissection, occlusion of a major epicardial artery or a side branch occlusion or thrombus, disruption of collateral flow, or distal embolization
Coronary Artery Bypass Grafting (CABG)-Related Myocardial Infarction
CABG 相關 MI 被任意定義為基線 cTn 值正常的患者中 cTn 值升高 > 99% URL 的 10 倍。對於術前 cTn 升高但 cTn 水平穩定（≤20% 變異）或下降的患者，術後 cTn 必須升高 >20%。但是，絕對後處理值仍然必須大於第 99 個百分位數 URL 的十倍。此外，還需要以下元素之一：
CABG-related MI is arbitrarily defined as an elevation of cTn values >10 times the 99th percentile URL in patients with normal baseline cTn values. In patients with elevated pre-procedure cTn in whom cTn levels are stable (≤20% variation) or falling, the post-procedure cTn must rise by >20%. However, the absolute post-procedural value still must be greater than ten times the 99th percentile URL. In addition, one of the following elements is required:
新病理Q波的發展
血管造影記錄新的移植物閉塞或新的自體冠狀動脈閉塞
影像學證據顯示新的存活心肌喪失或新的局部室壁運動異常，其模式與缺血性病因一致
Development of new pathological Q waves
Angiographic documented new graft occlusion or new native coronary artery occlusion
Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology
臨床意義
心臟事件的準確診斷和治療是急診科工作的重要組成部分。 [16] 肌鈣蛋白檢測的發展和實施對急診醫學的實踐產生了巨大的影響。 [29] 重要的是要認識到使用肌鈣蛋白測試時的缺點和潛在缺陷，並在做出醫療決策時牢記整個臨床情況。 [96] 肌鈣蛋白測試改變了急救醫學的實踐方式，深入了解其臨床意義對於急救人員的成功至關重要。 [28]
Clinical Significance
The accurate diagnosis and treatment of cardiac events is an essential component of working in the emergency department.[16] The development and implementation of troponin testing have had a massive influence on the practice of emergency medicine.[29] It is important to recognize the drawbacks and potential flaws when using troponin testing and to keep the entire clinical picture in mind when making medical decisions.[96] Troponin testing has changed how emergency medicine is practiced, and a deep understanding of its clinical implications is critical to the success of emergency providers.[28]
肌鈣蛋白水平升高應始終在臨床背景下進行評估。 [97] 除心肌梗死外，導致肌鈣蛋白升高的原因包括：心肌炎、心包炎、心臟挫傷或外傷、主動脈夾層、心內膜炎、心臟手術、肺栓塞、中風（缺血性或出血性）、心肺復蘇(CPR)、除顫、慢性嚴重心力衰竭、心律失常（快速心律失常、緩慢性心律失常、心臟傳導阻滯）、敗血症、腎功能衰竭、肥厚性梗阻性心肌病（HOCM）、章魚壺心肌病、燒傷、極度勞累、心臟手術後、浸潤性疾病如澱粉樣變性、藥物（阿黴素、曲妥珠單抗）、蛇毒、移植血管病變和危重疾病。
Elevated troponin levels should always be evaluated in a clinical context.[97] Causes of troponin elevation other than MI include the following: myocarditis, pericarditis, cardiac contusion or trauma, aortic dissection, endocarditis, cardiac surgery, pulmonary embolism, stroke (ischemic or hemorrhagic), cardiopulmonary resuscitation (CPR), defibrillation, chronic severe heart failure, cardiac arrhythmias (tachyarrhythmias, bradyarrhythmias, heart blocks), sepsis, renal failure, hypertrophic obstructive cardiomyopathy (HOCM), takotsubo cardiomyopathy, burns, extreme exertion, post–cardiac surgery, infiltrative diseases such as amyloidosis, medications (doxorubicin, trastuzumab), snake venom, transplant vasculopathy, and critical illness.
下圖來自(Figure 3 - uploaded by Terry Elton) (與上面文字資料非同一來源)
下面轉貼自臨床筆記
臨床筆記 2021-03-31
心肌鈣蛋白 (cTn )的臨床意義
心肌長時間的缺氧導致心肌死亡，是梗塞的病理學所見。心肌死亡的特徵有凝固性的心肌細胞分解(coagulative myocytolysis)，及收縮環帶(contraction band)壞死。心肌缺氧並不會立即造成細胞死亡，在某些動物實驗得知，至少需要20分鐘。6-12小時後，肉眼可見壞死之外觀，若顯微鏡觀察下，2-3小時之後就可以看到心肌壞死的現象。心肌完全壞死至少需要2至4小時，但會受以下因素影響：是否有側支循環供血至梗塞部位，持續或間斷的冠狀動脈阻塞，心肌對於缺血的敏感度，發生梗塞前之狀況，以及各別心肌細胞對於血氧與養份的不同需求度。
由梗塞面積的大小可以將心肌梗塞區分為極微小(microscopic)的局部壞死，小區域(梗塞面積小於左心室的10%)，中區域(梗塞面積佔左心室的10-30%)，及大區域(梗塞面積大於左心室的30%)。梗塞之後的癒合至少需要5至6週。
心肌生化標記的升高
鈣蛋白複合體(troponin complex)是經由鈣離子是調節橫紋肌的收縮，含有三種小單位結構，包括鈣蛋白C (troponin C)，用來與鈣離子結合；心肌鈣蛋白I (cTn I)與心肌的肌動蛋白(actin)結合而抑制肌動蛋白與肌蛋白質(myosin)的互相作用；心肌鈣蛋白T (cTn T)則與非水溶性肌蛋白質(tropomyosin)結合，然後依附於鈣蛋白複合體連接至心肌之薄細絲(thin filament)。當心肌死亡之後，cTn T及cTn I直接被分解釋出，在血中即可測得數據。
當心肌死亡之後會釋放出不同的蛋白質，在血清裡可以偵測到cTn、肌氨酸磷酸酶(creatinine phosphokinase, CK)、 乳酸去氧酶(lactate dehydrogenase, LDH)等各種不同蛋白酶。但這些蛋白酶的升高，並非心肌缺氧專一性，非缺血性心臟病的疾病也會使它們升高，因此偵測心肌特有的生化標記對於心肌梗塞的診斷將會提供更精密的判讀。其中cTn是最敏感且專一的心肌生化標記，尤其cTn T及cTnI，是目前診斷心肌梗塞的診斷要件之一，即使是極微小區域的梗塞，均能測出。同時CK總值，LDH總值及同化酶，天門冬氨酸轉氨酶(aspartate aminotransferase, AST)都不建議再用來測定心肌缺氧或梗塞。
心肌收縮的蛋白結構發生心肌缺氧導致壞死時，cTn就從心肌細胞被分解釋放出來。其中cTn T及 cTn I是心肌的生化標記，具有極高度的敏感性與專一性，除了腎末期疾病之外，cTn的升高可代表心肌缺氧。臨床出現心肌缺氧症狀後之2至4小時，cTn開始升高，24-48小時達到高峰值。cTn升高狀態可持續5-10天，cTnT升高可持續5-14天。這種急速上升且維持數日的概念可用來區分心肌缺氧是否急性或慢性，或者是再次梗塞(reinfarction)。
心肌生化標記(cTn)的檢測初質評估，3－6小時後再追蹤檢測。臨床症狀與抽血檢測時刻有關，尤其要配合數據的起落之判讀。
腎末期疾病患者之cTn呈現的是慢性升高的狀態，而且cTn T上升數值超過cTn I。
最佳精準化的cTn分析值是採用URL的99百分位值，且差異係數(coefficient of variation, CV) <10%。參考值上限(URL)，是以正常對照組的99百分位值，各儀器公司提供自己的數據，因此每間醫院的cTn參考值不盡相同。雖然正常對照組的正常性如何，至今仍有不少疑問，但大多數專家學者及學術機構均同意以URL的99百分位值，且CV<10%作為研究分析心肌梗塞的基本共識。
cTn的檢測應每3-6小時追蹤複檢，對於心衰竭與腎末期疾病者雖然呈現慢性升高的狀態，除非發生急性心肌梗塞，否則不會突然急劇上升。升高的cTn值(>URL的99百分位值)無論是否呈現動態性變化，或者臨床亦無心肌缺氧的現象，都應立即尋找其他與心肌損傷之診斷，例如：心肌炎、主動脈剝離、肺栓塞或心衰竭。另外可以導致cTn升高的疾病。
延伸閱讀……
急性心肌梗塞的定義與分類：2018 ESC/ACC/AHA
https://reurl.cc/pmVDzb
#心肌鈣蛋白 (#cTn )的臨床意義
Ref:
1. J Am Coll Cardiol 2007;50:2173–95.
2. J Am Coll Cardiol 2012;60:1581-98
3. Fourth universal definition of myocardial infarction (2018). European Heart Journal (2019) 40, 237–269
#cTn
#AMI
#心肌鈣蛋白
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