Blake Wachter Spring 2009 蛸壺 Case Presentation 57 year old women presenting to the ED with complaint of 2 hours of crushing pressurelike chest pain non radiating She says she feels short of breath and diaphoretic but denies nausea and vomiting She does not have a family or personal hi ID: 804538
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Slide1
Takotsubo Cardiomyopathy
Blake Wachter, Spring 2009
蛸壺
Slide2Case Presentation
57 year old women presenting to the ED with complaint of 2 hours of crushing pressure-like chest pain, non radiating. She says she feels short of breath and diaphoretic but denies nausea and vomiting. She does not have a family or personal history of heart disease. She denies a life long history of smoking. Her past medical history is significant for obesity, DM II, OA. She takes
metformin
and
occ
NSAIDS.
Slide3Slide4Labs
CBC - normalChem 14 – normal except glucose of 203Troponin
I in ER 0.9
CK-MB 6.7
Slide5Our patient’s pain is now controlled with the nitro and morphine she got in the ER. We have talked with the interventional cardiologist and she will be going to the cath lab now.
Meanwhile …
Slide6Differential Diagnosis
Coronary artery disease with acute plaque ruptureCoronary artery spasmMicrovascular disease of the coronaries
Drugs (Cocaine)
Takotsubo cardiomyopathy
Our patient is back
Slide7Slide8Slide9Slide10Call it what you like…
Takotsubo cardiomyopathyTransient apical ballooningApical ballooning cardiomyopathy
Stress-induced cardiomyopathy
Broken heart syndrome
Slide11Outline
History of Takotsubo cardiomyopathyDiagnostic criteria Clinical presentationPathophysiology
Management
Prognosis
Slide12Significance
Takotsubo cardiomyopathy is thought to account for 0.5-2% of all suspected acute myocardial infarction
Slide13Takotsubo Cardiomyopathy History
1970’s researchers and physicians first described reversible toxic effects of catecholamines on the heart1990, Sato et al first described a reversible
tako-tusbo
like left ventricular dysfunction (
Kagakuhyouronsha
; 1990:56-64)
Slide14Slide15Left ventriculogram
of the patient during systole showing mid, distal and apical left ventricular ballooning, with vigorous contraction of the basal segment
Slide16Tako Tsubo
Tako
Octopus
Tsubo
Medieval Japanese ceramic jar shaped with a wide body and narrow mouth
Originally used to store seeds
Tako-tsubo
Japanese octopus trap
Slide17蛸壺
Slide18Slide19Why haven’t I heard of this?
Slide20Slide21Case descriptions
Review articlesRetrospective studiesProspective studies
Slide22Diagnostic Criteria
Transient wall motion abnormalities that extend beyond a single vascular distributionECG changes
Modest elevation in cardiac enzymes
Frequently but not always, a stressful trigger
Exclusion criteria:
Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture
The absence of pheochromocytoma, subarachnoid hemorrhage, and myocarditis
Slide23Source publications
Year
Author
Country
#
Time
Type
Focus
2001
Tsuchihashi
Japan
88
9 yrs
Retro
Descriptive
2002
Kurisu
Japan
30
18 yrs
Retro
Descriptive
2005
Witstein
US
19
4 yrs
Pro
Describe the
neurohumoral
features
2005
Inoue
Japan
18
5 yrs
Retro
Compare to
LAD STEMI
2006
Sato
Japan
16
4 yrs
Retro
Stress as a precursor
2007
Kurowski
Germany
35
2 yrs
Pro
Compare to
LAD STEMI
Slide24Clinical Features
Predominantly women (80-100%)Post menopausal (Mean age: 61-76)Identifiable preceding stressor (14-100%)
Chest pain (54-100%)
ECG changes (56-100%)
Elevated cardiac enzymes (56-100%)
Normal coronaries (83-100%)
Slide25Clinical features
Long QTc (mean 501 – 542ms)Reduced EF at presentation (mean LVEF 29-49%)
Recovered EF at discharge (mean LVEF 63-76%)
Pulmonary edema (0-44%)
Intraaortic
balloon pump (0-18%)
Inducible
multivessel
spasm (0-43%)
Death(4 deaths)
Severe sepsis, PE
Slide26Wittstein
, I. S., D. R. Thiemann, et al. (2005). "
Neurohumoral
features of myocardial stunning due to sudden emotional stress." N
Engl
J Med 352(6): 539-48.
Slide27Stress?
Slide28Takotsubo cardiomyopathy: A Stress-induced cardiomyopathy
Niigata was shaken by a series of three earthquakes on 23 October 2004 and 90 aftershocks during the following week25 cases of Takotsubo’s cardiomyopathy in the 4 weeks following the earthquake compared to 1 case in the 4 weeks prior none in 2003 and one in 2002
All recovered within several weeks following the improvement of apical dysfunction
Slide29Other stressors
Status asthmaticusChild birth (C-Section)Strenuous exercise (cardiac stress test)
Sick child
Mopping the floor
Argument with supervisor
Watching/Attending the World Cup Soccer
Sexual intercourse
Fixing a neighbor’s car
Severe illness
Public speaking (beware seniors!)
Slide30Slide31Pathophysiology
Slide32Cardiac biopsy
Interstitial infiltrates of mononuclear lymphocytes, leukocytes, macrophagesMyocardial fibrosisContraction bands with or without overt myocyte necrosis
Slide33Acute MI
Takotsubo
M., R. J.
Wiechmann
, et al. (1995). "Cardiac beta-adrenergic
neuroeffector
systems in acute myocardial dysfunction related to brain injury. Evidence for catecholamine-mediated myocardial damage." Circulation 92(8): 2183-9.
Slide34Mild mononuclear cell infiltration
Kurisu
, S., H. Sato, et al. (2002). "
Tako
-
tsubo
-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction." Am Heart J 143(3): 448-55.
Slide35Theories to explain the unique wall motion abnormalities of takotsubo cardiomyopathy
Multivessel Epicardial Coronary Artery SpasmCoronary microvascular impairment
Catecholamine cardiotoxicity
Neurogenic stunned myocardium
Slide36Theory 1: Multivessel Epicardial Coronary Artery Spasm
Regionally stunned myocardium results from coronary artery spasmIf no observed spontaneous spasm then impaired blood flow is caused by a vulnerable plaque rupture
Slide37Theory 1: Multivessel Epicardial Coronary Artery Spasm
Discrepancy between severe apical ventricular dysfunction and slightly increased cardiac enzymesPlaque rupture would not be expected to extend beyond the perfusion territory supplied by the artery
Ischemic stunning does not produce the histological changes
Spasms of vessels are not consistently seen in takotsubo cardiomyopathy
Slide38Cardiac MRI of myocardial viability
Wittstein, I. S., D. R. Thiemann, et al. (2005). "
Neurohumoral
features of myocardial stunning due to sudden emotional stress." N
Engl
J Med 352(6): 539-48.
Slide39Theory 2: Coronary microvascular impairment
In the setting of a normal coronary cath, microvascular disturbances could explain the expanded area of distribution
Impaired perfusion on thallium stress and PET
Correlation between microvascular dysfunction and severity of myonecrosis and ECG abnormalities
Slide40Stunned myocardium
Tsuchihashi
, K., K.
Ueshima
, et al. (2001). "Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris-Myocardial Infarction Investigations in Japan." J Am
Coll
Cardiol
38(1): 11-8.
Slide41Coronary flow velocity spectra
Kume
, T., T.
Akasaka
, et al. (2005). "Assessment of coronary microcirculation in patients with takotsubo-like left ventricular dysfunction." Circ J 69(8): 934-9.
DDT: Deceleration time of diastolic velocity
Slide42Theory 2: Coronary microvascular impairment
Which came first?Microvascular abnormalities resulting
from the mechanical wall stress
Microvascular abnormalities
causing
the mechanical wall stress
Slide43Theory 3: Catecholamine cardiotoxicity
Patients with pheochromocytoma are known to have reversible cardiomyopathyCirculating serum catecholamines cause a direct myocyte injury
Takotsubo cardiomyopathy and catecholamine cardiotoxicity have common histological changes
Slide44Wittstein
, I. S., D. R. Thiemann, et al. (2005). "
Neurohumoral
features of myocardial stunning due to sudden emotional stress." N
Engl
J Med 352(6): 539-48.
Slide45Beta receptors
http://www.cvpharmacology.com/cardioinhibitory/beta-blockers.htm
Slide46Review
Norepinephrine: Beta 1 adrenoceptors
Myocardium
G-s protein
positive inotropic responses
Epinephrine:
Beta 2 adrenoceptors
Smooth muscles
G-s protein
vasodilatation
Myocardium
G-s protein
positive inotropic responses
Beta 1 adrenoceptors
Myocardium
G-s protein
positive inotropic responses
Slide47Theory 3: Catecholamine cardiotoxicity
Beta 2 adrenoceptors found on apex of left ventricle4:1 (B1:B2)
Epinephrine surges
Beta 2-Gs protein coupling switches to a Beta 2-Gi protein coupling
Beta 2-Gi pathway
Negative inotropic responses
Epinephrine levels decrease
Beta 2-Gi protein coupling switches back or is degraded
Protective
High levels PKA of the Beta 1-Gs and Beta 2-Gs pathway causes apoptosis
Slide48Lyon, A. R., P. S. Rees, et al. (2008). "Stress (Takotsubo) cardiomyopathy--a novel
pathophysiological
hypothesis to explain catecholamine-induced acute myocardial stunning." Nat
Clin
Pract
Cardiovasc
Med 5(1): 22-9.
Slide49Theory 3: Catecholamine cardiotoxicity
Not all patients diagnosed with takotsubo cardiomyopathy have elevated catecholamines
Slide50Theory 4: Neurogenic stunned myocardium
Stroke and subarachnoid hemorrhages are known to cause cardiac stunningSympathetic activation on the heart results in a local norepinephrine surge
Sympathectomy has been shown to prevent brain-mediated cardiac injury
Evidence that apical myocardium has enhanced responsiveness to sympathetic stimulation which may cause the characteristic apical ballooning
Slide51Alpha 2 receptor
NET/Uptake-1
Slide52Theory 4: Neurogenic stunned myocardium
Basal segment of the left ventricle has greater density of sympathetic nervesHigh levels of catecholamines can interfere with the uptake of Norepinephrine via a
presynaptic
Norepi
transporter/ uptake-1
Left ventricular apex has greater # of Beta 1 adrenoceptors compared to the base
With high catecholamines
Decreased number of beta receptors
Decrease responsiveness of beta receptors
Slide53Slide54Why women?
MENHigher levels of basal sympathetic activityHigher catecholamine levels in response to emotional stress
More susceptible to catecholamine vasoconstriction
Women
More vulnerable to sympathetic mediated myocardial stunning thought secondary to the catecholamine surge
Role of Estrogen?
Slide55Current research
The rat modelImmobilization is known to cause stress induced catecholamine surges resulting in catecholamine cardiomyopathy
Role of estrogen?
Reduced estrogen induced a vulnerability to stress
Estrogen supplementation reduced incidence of ischemia and arrhythmias
Estrogen causes an increase in Beta 1 adrenoceptors
Decrease in estrogen alters the B1:B2 ratio
Species differences?
Slide56Emotional or Physical Trigger
Neurohormonal
surge of NE
Adrenal catecholamine surge Epi
Inhibit the uptake of NE via
NET/uptake – 1 channels
NE acts on B1 receptors
B1/Gs pathway creates high levels of PKA
Apoptosis of cells / decrease responsiveness
Decrease number of B1 receptors
Epi acts on B2 receptors
B2/Gs coupling switches to B2/Gi coupling
Decreased inotropic response on left ventricular apex
Decreased Estrogen?
Slide57Management
SupportiveTreat the heart failureDiuretics
Balloon pump if necessary
Consider LVAD
Avoid catecholamines for BP support
Monitor for arrhythmias associated with long QT
Treat alpha and beta blockers together ?
Beta blockers can stimulate the switching of B2-Gs to B2-Gi
High levels of epinephrine can be
prothrombolitic
Controversial to treat with anticoagulation
Estrogen?
Slide58Prognosis
Generally very good!Few fatalities but most were not associated with cardiovascular eventsNormalized LV function within weeks
Normalized ECG within months
Low recurrence rate of about 2% (so far)
Slide59References
Akashi, Y. J., D. S. Goldstein, et al. (2008). "Takotsubo cardiomyopathy: a new form of acute, reversible heart failure." Circulation 118(25): 2754-62.
Iga
, K., H. Gen, et al. (1989). "Reversible left ventricular wall motion impairment caused by pheochromocytoma--a case report."
Jpn
Circ J 53(7): 813-8.
Inoue, M., M. Shimizu, et al. (2005). "Differentiation between patients with takotsubo cardiomyopathy and those with anterior acute myocardial infarction." Circ J 69(1): 89-94.
Jayawardena
, S., D.
Sooriabalan
, et al. (2008). "Takotsubo cardiomyopathy in a 68-year old Russian female." Cases J 1(1): 64.
Kume
, T., T.
Akasaka
, et al. (2005). "Assessment of coronary microcirculation in patients with takotsubo-like left ventricular dysfunction." Circ J 69(8): 934-9.
Kurisu
, S., H. Sato, et al. (2002). "
Tako
-
tsubo
-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction." Am Heart J 143(3): 448-55.
Kurowski
, V., A. Kaiser, et al. (2007). "Apical and
midventricular
transient left ventricular dysfunction syndrome (
tako-tsubo
cardiomyopathy): frequency, mechanisms, and prognosis." Chest 132(3): 809-16.
Lyon, A. R., P. S. Rees, et al. (2008). "Stress (Takotsubo) cardiomyopathy--a novel
pathophysiological
hypothesis to explain catecholamine-induced acute myocardial stunning." Nat
Clin
Pract
Cardiovasc
Med 5(1): 22-9.
Sato, M., S. Fujita, et al. (2006). "Increased incidence of transient left ventricular apical ballooning (so-called 'Takotsubo' cardiomyopathy) after the mid-Niigata Prefecture earthquake." Circ J 70(8): 947-53.
Tsuchihashi
, K., K.
Ueshima
, et al. (2001). "Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris-Myocardial Infarction Investigations in Japan." J Am
Coll
Cardiol
38(1): 11-8.
M., R. J.
Wiechmann
, et al. (1995). "Cardiac beta-adrenergic
neuroeffector
systems in acute myocardial dysfunction related to brain injury. Evidence for catecholamine-mediated myocardial damage." Circulation 92(8): 2183-9.
Wilbert-
Lampen
, U., D.
Leistner
, et al. (2008). "Cardiovascular events during World Cup soccer." N
Engl
J Med 358(5): 475-83.
Wittstein
, I. S., D. R. Thiemann, et al. (2005). "
Neurohumoral
features of myocardial stunning due to sudden emotional stress." N
Engl
J Med 352(6): 539-48.
Yoshida, T., T. Hibino, et al. (2007). "A
pathophysiologic
study of
tako-tsubo
cardiomyopathy with F-18
fluorodeoxyglucose
positron emission tomography."
Eur
Heart J 28(21): 2598-604.
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