应激性心肌病StressInducedCardiomyopathy.pptx

Stress-Induced Cardiomyopathy(Tako-tsubo syndrome)應激性心肌病應激性心肌病 澳門澳門 鏡湖醫院心內科鏡湖醫院心內科金金 椿椿病情介紹病情介紹女性，70歲 (住院號：08-4361)主訴：胸痛1小時。AED(2008.2.28 21:45)：BP 156/84mmHg,HR 90bpm EKG 2008.2.28 21:542008.2.28 23:372008.2.29 08:13心肌酶譜變化心肌酶譜變化 參考值參考值參考值參考值日期日期日期日期CKCK(96-(96-140U/L)140U/L)CKMBCKMB(25U/L)(25U/L)TNTTNT(0.1ng/ml)(30min30min檢查：心電圖有動態變化，血心肌酶檢查：心電圖有動態變化，血心肌酶 CAGCAG：冠脈無明顯狹窄：冠脈無明顯狹窄EchoEcho：心尖摶動瀰漫性減弱，各房室不大：心尖摶動瀰漫性減弱，各房室不大住院期間：生命體征平穩，無心衰及心律失常住院期間：生命體征平穩，無心衰及心律失常Stress-Induced Cardiomyopathy(Tako-tsubo syndrome)應激性心肌病應激性心肌病 In 1990 Hikaru Sato and colleagues from Japan described a novel cardiac syndrome,characterised by:transient left ventricular dysfunction with chest pain,transient left ventricular dysfunction with chest pain,ECG changes ECG changes minimal release of myocardial enzymes minimal release of myocardial enzymes mimicking an AMI mimicking an AMI Left ventriculogram revealed:left ventricle had a Left ventriculogram revealed:left ventricle had a peculiar shape(a round bottom and narrow neck)peculiar shape(a round bottom and narrow neck)resembled a type of bottle used in Japan for trapping resembled a type of bottle used in Japan for trapping octopus.octopus.Sato and colleagues termed the syndrome Tako-Sato and colleagues termed the syndrome Tako-tsubo cardiomyopathy tsubo cardiomyopathy “takotako”meaning octopus,and meaning octopus,and“tsubotsubo”,bottle.,bottle.LV ventricular angiogram with typical apical LV ventricular angiogram with typical apical ballooning.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 Stress appears to be key to the development of Tako-tsubo:Tako-tsubo:can be emotional,physical or psychological in nature can be emotional,physical or psychological in nature Studies show Tako-tsubo has occurred:Studies show Tako-tsubo has occurred:after earthquakes after earthquakes death of a relative death of a relative car accidents car accidents surprise parties surprise parties fierce arguments fierce arguments court appearances and armed robberies court appearances and armed robberies Clinical features Chest pain is the most common symptom-up to 90%Chest pain is the most common symptom-up to 90%dyspnoea dyspnoea palpitations palpitations syncope syncopeAs with AMI features of high circulating adrenaline As with AMI features of high circulating adrenaline levels(such as diaphoresis and peripheral shutdown)levels(such as diaphoresis and peripheral shutdown)are also commonare also common Requiring IABP counterpulsation and mechanical Requiring IABP counterpulsation and mechanical ventilation(1-5%)ventilation(1-5%)Other complications are rare:left ventricular thrombus Other complications are rare:left ventricular thrombus formation,ventricular rupture and intractable formation,ventricular rupture and intractable arrhythmias arrhythmias ECG changes ECG changes on admission are ECG changes on admission are often indistinguishable from often indistinguishable from acute anterior myocardial acute anterior myocardial infarctioninfarction ST elevation,usually in V3 ST elevation,usually in V3 V6,V6,with evolving T-wave inversion,with evolving T-wave inversion,Later in the course(after 3Later in the course(after 3 days),days),widespread deep T-wave widespread deep T-wave inversion is often seen with inversion is often seen with significant QT prolongationsignificant QT prolongation Cardiac biomarkerSerial troponin 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 without 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(End-diastolic and end-systolic frames of the LV(A A and and B B)and RV()and RV(C C and and D D)demonstrating extent of LV and RV dysfunction(arrows).)demonstrating extent of LV and RV dysfunction(arrows).Echocardiogram Apical two chamber Apical two chamber echocardiographic echocardiographic view showing LV view showing LV apical ballooning and apical ballooning and sigmoid septum sigmoid septum End-diastolic and end-systolic apical four-and-two chamber End-diastolic and end-systolic apical four-and-two chamber echocardiographic views demonstrating the typical apical and mid-echocardiographic views demonstrating the typical apical and mid-ventricular LV wall-motion abnormalities of a patient with takotsubo ventricular LV wall-motion abnormalities of a patient with takotsubo cardiomyopathy cardiomyopathy 14 studies:14 studies:2%of ST elevation infarcts,2%of ST elevation infarcts,most cases in post-menopausal women.most cases in post-menopausal women.chest pain and dyspnoea in 67.8 and 17.8%chest pain and dyspnoea in 67.8 and 17.8%Cardiogenic shock(4.2%)Cardiogenic shock(4.2%)ventricular fibrillation(1.5%)ventricular fibrillation(1.5%)ST-segment elevation(81.6%)ST-segment elevation(81.6%)T wave abnormalities(64.3%)T wave abnormalities(64.3%)Q waves(31.8%)Q waves(31.8%)Cardiac biomarkers mildly elevated(86.2%)Cardiac biomarkers mildly elevated(86.2%)LV dysfunction on admission EF 20 to 49%,over a period of days LV dysfunction on admission EF 20 to 49%,over a period of days to weeks.to weeks.preceded by emotional(26.8%)or physical stress(37.8%).preceded by emotional(26.8%)or physical stress(37.8%).Norepinephrine concentration was elevated(74.3%)Norepinephrine concentration was elevated(74.3%)excellent,with full recovery in most patients.excellent,with full recovery in most patients.In-hospital mortality was 1.1%.Only 3.5%of the patients In-hospital mortality was 1.1%.Only 3.5%of the patients experienced a recurrence.experienced a recurrence.Comparison between positron Comparison between positron emission tomography(emission tomography(A A,C C,and and E E)and single-photon)and single-photon emission computed emission computed tomography(tomography(B B,D D,and,and F F)images:metabolic image images:metabolic image revealed severely reduced F-18 revealed severely reduced F-18 fluorodeoxyglucose uptake in fluorodeoxyglucose uptake in the apical and mid-ventricular the apical and mid-ventricular segments compared with segments compared with perfusion abnormalities.(perfusion abnormalities.(A A and and B B)Horizontal long-axis;()Horizontal long-axis;(C C and and D D)vertical long-axis;()vertical long-axis;(E E and and F F)short-axis.)short-axis.Light microscopy Endomyocardial biopsy specimen:contraction-band necrosis Endomyocardial biopsy specimen:contraction-band necrosis(arrows)and small amounts of mononuclear cell infiltration(arrows)and small amounts of mononuclear cell infiltration(haematoxylin and eosin stain).(haematoxylin and eosin stain).(A A)Original magnification x100;()Original magnification x100;(B B)original magnification x200.original magnification x200.PAS staining(arrows)shows remarkable intracellular accumulation of PAS staining(arrows)shows remarkable intracellular accumulation of glycogen(glycogen(A A).After functional recovery only small amounts of glycogen).After functional recovery only small amounts of glycogen particularly around the nuclei of myocytes(arrows)were documented(particularly around the nuclei of myocytes(arrows)were documented(B B).).Electron microscopy Electron microscopy of Electron microscopy of acuteacute biopsies showing numerous biopsies showing numerous vacuoles of different sizes and vacuoles of different sizes and contents(myelin bodies,contents(myelin bodies,residual cellular products),loss residual cellular products),loss of contractile material,and of contractile material,and areas of non-specified areas of non-specified cytoplasm(cytoplasm(A A).The interstitial).The interstitial space was widened containing space was widened containing formation of cellular debris formation of cellular debris(B B).In the).In the acuteacute phase,phase,formation of myelin bodies formation of myelin bodies could be documented(could be documented(C C).In).In TTC contraction bands of TTC contraction bands of sarcomeres were found(sarcomeres were found(D D).).RecoveredRecovered biopsies showed a biopsies showed a nearly complete nearly complete rearrangement of contractile rearrangement of contractile material with regularly material with regularly distributed sarcomeres,normal distributed sarcomeres,normal nuclei,and mitochondria(nuclei,and mitochondria(E,E,F F).vac,vacuole;svac,small).vac,vacuole;svac,small vacuoles;N,nucleus;cyt,vacuoles;N,nucleus;cyt,cytoplasm;mit,mitochondria;cytoplasm;mit,mitochondria;cd,cellular debris;mb,myelies cd,cellular debris;mb,myelies bodies;sarc,sarcomeres;cb,bodies;sarc,sarcomeres;cb,contraction band.contraction band.Immunohistochemistry Immunohistochemistry of intracellular proteins(specific labelling green,phalloidin Immunohistochemistry of intracellular proteins(specific labelling green,phalloidin red,nuclei blue).-actinin was detected only in the border zone during TTC(red,nuclei blue).-actinin was detected only in the border zone during TTC(A A).After).After functional recovery a regular distribution was found(functional recovery a regular distribution was found(B B).N-terminal dystrophin).N-terminal dystrophin showed a decrease in TTC verifying a loss of protein-to-protein interaction(showed a decrease in TTC verifying a loss of protein-to-protein interaction(C C)in)in comparison with biopsies after functional recovery(comparison with biopsies after functional recovery(D D).C-terminal dystrophin was).C-terminal dystrophin was unaltered in TTC suggesting that integrity of the sarcolemma is maintained(unaltered in TTC suggesting that integrity of the sarcolemma is maintained(E,FE,F).).Connexin-43 showed a reduced cellConnexin-43 showed a reduced cell cell connection in TTC(cell connection in TTC(G G),whereas a myocardial),whereas a myocardial integrity was documented after functional recovery(integrity was documented after functional recovery(H H).).Immunolabelling for titin Immunolabelling for titin was performed using T12 was performed using T12(A,BA,B)and Tz1/Z2()and Tz1/Z2(C,DC,D).).F-actin(red)was F-actin(red)was visualized with TRITCvisualized with TRITCconjugated phalloidin and conjugated phalloidin and nuclei(blue)were nuclei(blue)were counterstained with Draq-counterstained with Draq-5.Note that titin in the 5.Note that titin in the acute stage(acute stage(A,CA,C)is)is either absent in the either absent in the central parts of the central parts of the myocytes or shows a myocytes or shows a punctuated pattern as punctuated pattern as compared with a clear compared with a clear cross-striated pattern of cross-striated pattern of labelling and higher labelling and higher expression levels in the expression levels in the recovery phase(recovery phase(B,DB,D).).Immunohistochemistry of extracellular proteins(specific Immunohistochemistry of extracellular proteins(specific labelling green,phalloidin red,nuclei blue).The ECM stained labelling green,phalloidin red,nuclei blue).The ECM stained by fibronectin(by fibronectin(A,BA,B)and collagen-1()and collagen-1(C,DC,D)was increased)was increased and the myocardial syncytium was separated.After and the myocardial syncytium was separated.After functional recovery,a decrease of extracellular proteins was functional recovery,a decrease of extracellular proteins was observed.Macrophages(arrows)showing inflammatory observed.Macrophages(arrows)showing inflammatory response were regionally accumulated in TTC(response were regionally accumulated in TTC(E,FE,F).Slight).Slight increase of T-lymphocytes(arrows)was regionally observed increase of T-lymphocytes(arrows)was regionally observed in TTC(in TTC(G,HG,H).).Pathophysiology precise mechanisms are unknown precise mechanisms are unknown catecholamine-mediated mechanisms with likely catecholamine-mediated mechanisms with likely mediation via cardiac sympathetic nerves.mediation via cardiac sympathetic nerves.Sudden surging catecholamine levels,can be Sudden surging catecholamine levels,can be precipitated by emotional or physical stress precipitated by emotional or physical stress Catecholamine levels are characteristically far Catecholamine levels are characteristically far higher than in matched patients higher than in matched patients catecholamine-mediated multivessel epicardial spasm,microvascular coronary spasm,or possible direct catecholamine-mediated myocyte injury.Pathophysiology Pathophysiology On myocardial biopsy,the histological appearances On myocardial biopsy,the histological appearances are very similar to contraction band necrosis seen in are very similar to contraction band necrosis seen in phaeochromocytomaphaeochromocytoma In a rodent model,TTC can be prevented with-or In a rodent model,TTC can be prevented with-or-blockade-blockade The more dense distribution of adrenoceptors at The more dense distribution of adrenoceptors at the apex might explain why the apex is affected the apex might explain why the apex is affected while the base is spared while the base is spared In addition,oestrogen downregulates cardiac In addition,oestrogen downregulates cardiac adrenoceptors and attenuates their response to adrenoceptors and attenuates their response to activation,providing a plausible reason why the activation,providing a plausible reason why the condition is largely confined to postmenopausal condition is largely confined to postmenopausal women women Mayo Clinic criteriaMayo Clinic criteria for tako-tsubo cardiomyopathyfor tako-tsubo cardiomyopathy 1,Transient,reversibleakinesisordyskinesisoftheleft1,Transient,reversibleakinesisordyskinesisoftheleftventricularapicalandmid-ventricularsegmentswithventricularapicalandmid-ventricularsegmentswithregionalwallmotionabnormalities.regionalwallmotionabnormalities.2,Absenceofobstructivecoronaryarterystenosis50%2,Absenceofobstructivecoronaryarterystenosis50%oftheluminaldiameterorangiographicevidenceofoftheluminaldiameterorangiographicevidenceofacuteplaquerupture.acuteplaquerupture.3,NewECGabnormalitiesconsistingofST-segment3,NewECGabnormalitiesconsistingofST-segmentelevationorT-waveinversion.elevationorT-waveinversion.Absence of:Absence of:recent head trauma recent head trauma recent head trauma recent head trauma intracranial bleeding intracranial bleeding intracranial bleeding intracranial bleeding phaeochromocytoma phaeochromocytoma phaeochromocytoma phaeochromocytoma obstructive epicardial coronary artery obstructive epicardial coronary artery obstructive epicardial coronary artery obstructive epicardial coronary artery diseasediseasediseasedis