应激性心肌病StressInducedCardiomyopathy课件

1、Stress-Induced Cardiomyopathy(Tako-tsubo syndrome)應激性心肌病 澳門 鏡湖醫院心內科金 椿病情介紹女性，70歲 (住院號：08-4361) 主訴：胸痛1小時。AED (2019.2.28 21:45)： BP 156/84mmHg, HR 90bpm EKG 2019.2.28 21:542019.2.28 23:372019.2.29 08:13心肌酶譜變化 參考值日期CK(96-140U/L)CKMB(25U/L)TNT(30min檢查：心電圖有動態變化，血心肌酶CAG：冠脈無明顯狹窄Echo：心尖摶動瀰漫性減弱，各房室不大住院期間：生命體

2、征平穩，無心衰及心律失常Stress-Induced Cardiomyopathy(Tako-tsubo syndrome)應激性心肌病 In 1990 Hikaru Sato and colleagues from Japan described a novel cardiac syndrome, characterised by:transient left ventricular dysfunction with chest pain, ECG changes minimal release of myocardial enzymes mimicking an AMI Left vent

3、riculogram revealed : left ventricle had a peculiar shape (a round bottom and narrow neck) resembled a type of bottle used in Japan for trapping octopus. Sato and colleagues termed the syndrome Tako-tsubo cardiomyopathy “tako” meaning octopus, and “tsubo”, bottle. LV ventricular angiogram with typic

4、al apical ballooning. More recently, it has also been called :acute left ventricular ballooningreversible stress cardiomyopathy broken heart syndrome stress-induced myocardial stunningApical ballooning syndromeStress appears to be key to the development of Tako-tsubo: can be emotional, physical or p

5、sychological in nature Studies show Tako-tsubo has occurred : after earthquakes death of a relative car accidents surprise parties fierce arguments court appearances and armed robberies Clinical features Chest pain is the most common symptom - up to 90% dyspnoea palpitations syncopeAs with AMI featu

6、res of high circulating adrenaline levels (such as diaphoresis and peripheral shutdown) are also common Requiring IABP counterpulsation and mechanical ventilation(1-5%) Other complications are rare: left ventricular thrombus formation, ventricular rupture and intractable arrhythmias ECG changes ECG

7、changes on admission are often indistinguishable from acute anterior myocardial infarction ST elevation, usually in V3V6, with evolving T-wave inversion, Later in the course (after 3days), widespread deep T-wave inversion is often seen with significant QT prolongation Cardiac biomarkerSerial troponi

8、n and ck-MB levels only a small rise this is an important difference from AMI. A small proportion of patients will have no troponin rise at all, and the absence of elevation does not exclude the diagnosis. Coronary angiography Upon admission coronary angiography revealed no or only a diffuse CAD wit

9、hout obstructive stenoses (50%), or spontaneous vasospasm in all patients Left ventriculography akinesia in the anterolateral, apical, diaphragmatic, septal areas as well as base hypercontractile The median EF of the LV was 30.4% . End-diastolic and end-systolic frames of the LV (A and B) and RV (C

10、and D) demonstrating extent of LV and RV dysfunction (arrows). Echocardiogram Apical two chamber echocardiographic view showing LV apical ballooning and sigmoid septum End-diastolic and end-systolic apical four-and-two chamber echocardiographic views demonstrating the typical apical and mid-ventricu

11、lar LV wall-motion abnormalities of a patient with takotsubo cardiomyopathy 14 studies:2% of ST elevation infarcts, most cases in post-menopausal women. chest pain and dyspnoea in 67.8 and 17.8% Cardiogenic shock (4.2%) ventricular fibrillation (1.5%)ST-segment elevation( 81.6%)T wave abnormalities(

12、 64.3%)Q waves( 31.8%)Cardiac biomarkers mildly elevated( 86.2%)LV dysfunction on admission EF 20 to 49%, over a period of days to weeks. preceded by emotional (26.8%) or physical stress (37.8%).Norepinephrine concentration was elevated ( 74.3% ) excellent, with full recovery in most patients. In-ho

13、spital mortality was 1.1%. Only 3.5% of the patients experienced a recurrence. Comparison between positron emission tomography (A, C, and E) and single-photon emission computed tomography (B, D, and F) images: metabolic image revealed severely reduced F-18 fluorodeoxyglucose uptake in the apical and

14、 mid-ventricular segments compared with perfusion abnormalities. (A and B) Horizontal long-axis; (C and D) vertical long-axis; (E and F) short-axis. Light microscopy Endomyocardial biopsy specimen: contraction-band necrosis (arrows) and small amounts of mononuclear cell infiltration (haematoxylin an

15、d eosin stain). (A) Original magnification x100; (B) original magnification x200. PAS staining (arrows) shows remarkable intracellular accumulation of glycogen (A). After functional recovery only small amounts of glycogen particularly around the nuclei of myocytes (arrows) were documented (B). Elect

16、ron microscopy Electron microscopy of acute biopsies showing numerous vacuoles of different sizes and contents (myelin bodies, residual cellular products), loss of contractile material, and areas of non-specified cytoplasm (A). The interstitial space was widened containing formation of cellular debr

17、is (B). In the acute phase, formation of myelin bodies could be documented (C). In TTC contraction bands of sarcomeres were found (D). Recovered biopsies showed a nearly complete rearrangement of contractile material with regularly distributed sarcomeres, normal nuclei, and mitochondria (E, F). vac,

18、 vacuole; svac, small vacuoles; N, nucleus; cyt, cytoplasm; mit, mitochondria; cd, cellular debris; mb, myelies bodies; sarc, sarcomeres; cb, contraction band. Immunohistochemistry Immunohistochemistry of intracellular proteins (specific labelling green, phalloidin red, nuclei blue). -actinin was de

19、tected only in the border zone during TTC (A). After functional recovery a regular distribution was found (B). N-terminal dystrophin showed a decrease in TTC verifying a loss of protein-to-protein interaction (C) in comparison with biopsies after functional recovery (D). C-terminal dystrophin was un

20、altered in TTC suggesting that integrity of the sarcolemma is maintained (E, F). Connexin-43 showed a reduced cellcell connection in TTC (G), whereas a myocardial integrity was documented after functional recovery (H). Immunolabelling for titin was performed using T12 (A, B) and Tz1/Z2 (C, D). F-act

21、in (red) was visualized with TRITCconjugated phalloidin and nuclei (blue) were counterstained with Draq-5. Note that titin in the acute stage (A, C) is either absent in the central parts of the myocytes or shows a punctuated pattern as compared with a clear cross-striated pattern of labelling and hi

22、gher expression levels in the recovery phase (B, D). Immunohistochemistry of extracellular proteins (specific labelling green, phalloidin red, nuclei blue). The ECM stained by fibronectin (A, B) and collagen-1 (C, D) was increased and the myocardial syncytium was separated. After functional recovery

23、, a decrease of extracellular proteins was observed. Macrophages (arrows) showing inflammatory response were regionally accumulated in TTC (E, F). Slight increase of T-lymphocytes (arrows) was regionally observed in TTC (G, H). Pathophysiology precise mechanisms are unknown catecholamine-mediated me

24、chanisms with likely mediation via cardiac sympathetic nerves.Sudden surging catecholamine levels, can be precipitated by emotional or physical stress Catecholamine levels are characteristically far higher than in matched patients catecholamine-mediated multivessel epicardial spasm, microvascular co

25、ronary spasm, or possible direct catecholamine-mediated myocyte injury. Pathophysiology Pathophysiology On myocardial biopsy, the histological appearances are very similar to contraction band necrosis seen in phaeochromocytoma In a rodent model, TTC can be prevented with - or -blockade The more dense distribution of adrenoceptors at the apex might explain why the apex is affected while the base is spared In addition, oestrogen downregulates cardiac adrenoceptors and attenuates their response to activation, providing a plausible reason why the condition is large