Takotsubo cardiomyopathy

copyright@drsudebmukherjee

Cardiomyopathy characterized by transient apical and

midventricular LV dysfunction in the absence of significant

coronary artery disease that is triggered by emotional or

physical stress.

In setting of depressed/abnormal function of distal and apical LV segments

there is compensatory hyperkinesis of basal walls “ballooning” of apex

during systole.


1st described in Japan in 1991Named after the tako-tsubo, which is an octopus trap

Shape of the trap is similar to the appearance of LV apical ballooning noted in patients with this form of cardiomyopathy

Was later described elsewhere as well and is being increasingly recognized.


Kurisu, S., et al. 2002. American Heart Journal. 143: 448-455.copyright@drsudebmukherjee

The Name

A Japanese term, named after the jar used for trapping octopuscopyright@drsudebmukherjee

In Popular Culture• A mechanism of being scared to death?

o Ananias and Sapphirao Legal

Larry Whitfield – on trial for 1st degree murder while holding 79F at gunpoint – “fear induced heart attack”

Willie Ingram – convicted of murder for “emotional upset” causing heart attack, a 64M

Mark Fisher – convicted of murder of 89F for “fear induced heart attack”


Takotsubo cardiomyopathy

Stress-induced cardiomyopathy

Transient left ventricular apical ballooning syndrome

Apical ballooning syndrome

Broken heart syndrome

Ampulla cardiomyopathy

Different Names:


May account for up to 2% of suspected ACS

In-hospital mortality ranges 0-8%

Much more common in women (~90%), especially

postmenopausal women (>80% of cases)

Mean age 58-75 years

Triggers: death of loved one, other catastrophic news,

devastating financial losses, natural disasters, physical

illness/ICU, etc.copyright@drsudebmukherjee

CHARACTERISED BY-

• An acute completely reversible systolic heart failure

• Typical: Apical akinesia [ballooning] and hypercontractile

base

• Atypical: Midventricular akinesia and hypercontractile base

• No relevant CAD

• Mimics symptoms of ACS


CLASSIFICATION

1. Takotsubo type: apical akinesia and basal hypercontraction;

2. Reverse takotsubo: basal akinesia and apical

hypercontraction;

3. Mid ventricular type: mid ventricular ballooning and

basal/apical hypercontraction

4. Localized type: any other segmental ballooning when

Takotsubo-like LV dysfunction is present.


ESC/HFA STATEMENT CLASSIFICATION


Causes/Epidemiology

• Triggered by extreme emotional or physical stress

o Deaths, accidents, surprise party, procedure,

arguments, legal, public speaking, armed robbery

• Strong predominance in postmenopausal women

• Under-recognized, ~2% of all ACS


Reported triggers• Emotional

• Death of a loved one (including pets)• Surprise party• Family member being arrested• Fierce argument• Robbery• Public speaking

• Surgery – Hysterectomy, Cholecystectomy• Stress echo with dobutamine• Opiate withdrawal• Thyrotoxicosis • Physical exhaustion ( triathlon, sexual, gym)- males


Pathophysiology

1. Coronary Spasm or Stunned myocardium:1. Not favoured

2. Wall involvement extends beyond single vascular territory

3. Few patients demonstrate spasm with provocation during

catheterization

4. CEs only slightly elevated, not high enough

2. Microvascular Impairment:1. Certainly present (As evident from several studies)

2. Correlative, but causation doubted


Pathophysiology

3. Catecholamine Cardiotoxicity1. Plasma levels of Epi/NE increased, even higher than

in pt’s w/ similar HF.

2. Not uniformly present, but close

3. Histological findings simliar to in other forms of

catecholamine cardiotoxicity

4. Pheochromocytoma can cause similar cardiac event


MECHANISM:

1) Apical-basal gradients of β-adrenergic receptors (βARs) and sympathetic

innervation in mammalian LV, where apex contains the highest βAR and

the lowest sympathetic nerve density. The presence of ventricular βAR

gradient results in increased apical responsiveness to catecholamines

predominantly epinephrine

2) Epinephrine, at high levels can have negative inotropic impact and trigger

a switch from intracellular trafficking, from Gs (stimulatory) protein to Gi

(inhibitory) protein signaling through the β2AR. This negative inotropic

affect is greatest in apex where the density of βARs is highest.


Pathophysiology

4) Transient coronary artery occlusion/reperfusion

episodes:

Some investigators observed that transients LV dysfunction can

be caused by atheromatous ruptured plaque that is not clearly

visible on coronary angiography ( animal model has failed to

support this hypothesis.)


Pathophysiology5) Oxidative stress response to excess catecholamine Recent studies suggest that oxidative stress in response to excess of

catecholamines may be the underlying mechanism of LV dysfunction in TC.

( lack of evidence - how oxygen free radicals are released: )

Directly in response to increased concentration of catecholamines ?

As a result of catecholamines provoked microvascular changes?

As a result of myocyte injury caused by various other mechanisms?


Pathophysiology

6) Relative deficiency of estrogen: Estrogen deficiency may be responsible for the development of TC.

Ueyama et al. showed that ovariectomized rats were more prone to a stress

and demonstrated higher increase of the heart rate and reduction in LV function

comparing to the rats that had estradiol supplementation .

Postmenopausal women lose the protective effect of estrogens which make

them more prone to the excess of circulating catecholamines.


Why Predominantly Women?Stress induces upregulation of--

Immediate early genes (IEGs),

Certain proto-oncogenes

Heat shock proteins

(transiently activated to rapidly adapt to a stressor BUT detrimental for CV

physiology)

Oestrogen minimises these factors.


Oestrogen?Oestrogen may also play a role in enhancing the β-adrenoreceptor

sensitivity and in promoting vasodilation.

Post-menopausal women have a decreased β-adrenoreceptor

responsiveness to catecholamine stimulation than younger females.

However, their α-adrenoreceptor vasoconstriction response to

catecholamines remains the same.

There is more β-adrenoreceptor stimulation in relation to β-

adrenoreceptor responsiveness thus leading to more vasoconstriction,

which in the setting of endothelial dysfunction may trigger TTC.


Why Less In Male?Males are better protected biologically against stress (strossberg et al)

METABOLIC THEOREY:

Oestrogen has also been implicated in maintaining appropriate glucose uptake for cardiac energy .

Female heart depends on glucose as its energy source more than the male heart

The relative lack of oestrogen as women age, therefore, may potentiate this attenuated glucose uptake thus predisposing postmenopausal females to TTC.

Males are not predisposed to TTC despite their relative lack of oestrogen because they are not as dependent on glucose as their preferential cardiac energy substrate.


Pathophysiology

7) Infective agent such as a viral illnessInfiltration by mononuclear lymphocytes and macrophages are usually

observed in histological examination of TC patients, nevertheless, no

infective agent has been successfully isolated from TC patients.

8) Genetic predispositionSome authors suggested genetic predisposition due to a reported familial

association, nevertheless no genetic studies supported genetic basis of this

disorder.


Pathophysiology


1. Transient a/dyskinesis of apical and midventricular segments in association with regional wall motion abnormalities that extend beyond the distribution of a single epicardial vessel

2. Absence on angiography of obstructive coronary artery disease or evidence of acute plaque rupture

3. New ST segment elevation or T wave inversions on ECG

4. Absence of recent significant head trauma, intracranial bleeding, pheochromocytoma, myocarditis, or hypertrophic cardiomyopathy

Proposed by Bybee, et al. 2004. Annals of Internal Medicine. 141: 858-865.copyright@drsudebmukherjee

Mayo clinic criteria:

1. Typical LV contraction pattern: transient hypokinesia, akinesis or dyskinesia in the LV mid segments with or without apical involvement accompanied with hypercontraction in the basal segments; RWMA that extend beyond a single coronary artery vascular distribution; stressful trigger is usually but not always present;

2. Absence of obstructive CAD or angiographic evidence of acute plaque rupture;

3. Newly developed ECG abnormalities (ST segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin;

4. Absence of recent head trauma, intracranial hemorrhage, pheochromocytoma, myocarditis or hypertrophic cardiomyopathy



Signs / Symptoms

• Think ACS

o CP, dyspnea, syncope, palpitaion, nausea , vomiting.

• Complications

o Pulmonary edema and respiratory failure

o Cardiogenic shock

o Ventricular tachyarrhythmias

o Ventricular wall rupture

o Mural thrombus


Substernal chest pain

ECG abnormalities

ST elevation (usually anterior precordial leads)- 82%

ST depression

T wave inversion

QT prolongation

Abnormal Q waves

Elevated cardiac biomarkers

Clue: Devoid of any traditional Risk Factors


Differential diagnosis• Acute Coronary Syndromes

• Acute Myocarditis

• Angina Pectoris

• Aortic Dissection

• Boerhaave Syndrome

• Cardiac Tamponade

• Cardiogenic Shock

• Cardiomyopathy (Cocaine/ Dilated /Hypertrophic)

• Coronary Artery Vasospasm


Tachyarrhythmias, bradyarrhythmias

Pulmonary edema

Cardiogenic shock

Transient LV outflow tract obstruction

Mitral valve dysfunction

Acute thrombus formation and stroke

Deathcopyright@drsudebmukherjee

COMPLICATION/MORTALITY


Because presentation is similar to ACS, proceed Accordingly.

LV ventriculogram and/or echocardiography can both be used to visualize apical ballooning with a/dyskinesis of apical ½ to ⅔ of the LV.

Average LV EF range 20-49% Can have “atypical” ballooning of the middle or basal portions of the

LV (much less common) Wall motion abnormalities typically involve the distribution of more

than one coronary artery Ventriculography and echocardiography also allow evaluation for LV

outflow tract obstruction (~16%).

Cardiac catheterization reveals lack of flow limiting coronary lesions or evidence of plaque rupture.


Lab Evaluation:

• CE: Normal or slightly elevated

• Elevated BNP

• High serum catecholamines.


EKGST Elevation, TWI, Prolonged QT


Copyright ©2007 BMJ Publishing Group Ltd.

Nef, H. M et al. Heart 2007;93:1309-1315

Figure 1 Selective coronary angiography. Left (A) and right (B) coronary arteries in a patient presenting with tako-tsubo cardiomyopathy, excluding coronary artery

disease. Left ventriculography during diastole (C) and systole (D) demonstrate the typical left ventricular apical ballooning and a hypercontractile base.


Typical

Atypical


Copyright ©2007 BMJ Publishing Group Ltd.

Nef, H. M et al. Heart 2007;93:1309-1315

Figure 4 Transthoracic echocardiogram showing four-chamber views during diastole (A) and systole (B) in a patient presenting with tako-tsubo cardiomyopathy. Real time

three-dimensional echocardiography shows the typical contractile pattern of tako-tsubo cardiomyopathy with akinesia of apical segments and hypercontractility of the

basal segments (diastole, C; systole, D).


Cardiac MRI The most characteristic finding is ventricular edema that appears as

high signal intensity with a diffuse or transmural distribution.

Moreover, the location of the edema is not related to a vascular territory

of coronary arteries, and edema is distributed in both the apical and mid

planes of the LV.

The area of edema shows dysfunction in the ventricular contraction

observed with cine MRI sequence.


MRI:


MRI In MI:


Supportive, conservative therapy

Hydrate, remove stress (if possible)

Treat LV dysfunction with standard heart failure regimen- including beta blocker, ACE inhibitor, diuretics (if volume overloaded), aspirin

Usually treated for ~6 months

For pts who are hypotensive with shock, perform echo to evaluate for LVOT obstruction.

No LVOT obstruction inotropes, IABP if needed +LVOT obstruction NO inotropes (can worsen obstruction), use

beta blockers (+/- α agonist Phenylephrine), IABP if needed +/- fluid resuscitation (evaluate pulmonary status)


Treatment

Supportive care according to complications• Arrhythmias• Cardiogenic shock• Pulmonary edema

Careful use of pressors



Prognosis

• 95% complete recovery within 4-8 weeks.• 3% recurrence • Complications

• Death 1%• Left heart failure with and without pulmonary edema• Cardiogenic shock• Left ventricular outflow obstruction• Mitral regurgitation• Ventricular arrhythmias• Left ventricular mural thrombus formation• Left ventricular free-wall rupture


Takotsubo cardiomyopathy is a syndrome of transient dysfunction of

apical/midventricular LV with compensatory hyperkinesis of basal

segment resulting in apical ballooning.

It is triggered by significant emotional or physical stress.

It is more common in post-menopausal women.

Presentation is similar to MI (symptoms, ECG changes, and biomarker

elevations). Accounts for ~1-2% of suspected ACS cases.

No significant coronary artery disease or evidence of plaque rupture can be identified.

LV function recovers, typically within 4 weeks.


A 75 year old woman presents with pneumonia and chest pain

Case study

In the last 24 hours, she has experienced: Dyspnea Sputum production Fever CoughShe presents to the ER for evaluation


T 101.2, BP 100/65, HR 110 (sinus tachycardia)

Diffuse rhonchi, decreased breath sounds left base

S1, S2 normal, No murmur, S3, S4

CXR: Infiltrate left lower lobe c/w pneumonia


ECG


Nef HM, et al. Tako-tsubo Cardiomyopathy (Apical Ballooning). Heart. 2007; 93:1309-1315.


Case

a) She will need symptom limited stress test in 3-4 weeks

to determine prognosis

b) Biventricular pacing will improve prognosis.

c) Overall prognosis is poor given the severe LV

dysfunction.

d) Overall prognosis is good. She should have significant

improvement in LV function within 4 weeks.


Answer

d. Overall prognosis is good. She should have

significant improvement in LV function within 4

weeks.

She has stress induced cardiomyopathy.

Takotsubo Cardiomyopathy, Apical ballooning

syndrome


THANK YOU


Health & Medicine

Takotsubo cardiomyopathy