Broken heart syndrome pdf

Presenter :- DR.Rajesh M. Dandale Università degli Studi di Verona

A 64 year-old post-menopausal female presented with

sudden onset of chest discomfort which started after

she experienced severe emotional stress. She was

transported to Department of Cardiology by Emergency

Service. The pain resolved with administration of

sublingual nitroglycerin during transportation .

She was dyslipidemic, non diabetic, non HTN, no P/H

of MI.

No history of similar episodes in other family

members.

Initial electrocardiogram revealed sinus bradycardia with

diffuse ST – segement elevation, QRS and and QT interval

prolongation.

CK-MB -13,5 ug/L. Troponin I- 1.02 ug/L (ULN: <0.5).

Chest X-ray: WNL

Akinetic apical and anteroseptal wall with reduction in EF. Minimal MR

1. Acute coronary syndrome?

2. Aborted myocardial infarction? (no detectable

myocardial injury)

3. Myocarditis?

4. Myocardial dysfunction?

5. Apical ballooning syndrome?

In hospital day 4,ECG and cardiac biomarker normalized,

TTE after 7 days show no RWM abnormality and EF-60%

Patient was discharged from hospital with healthy condition,

advised for regular follow up.

Tako-Tsubo cardiomyopathy

Apical ballooning syndrome

Stress cardiomyopathy

Ampulla cardiomyopathy

Neurological cardiomyopathy (stunning)

Broken heart syndromeInt J Cardiol 2007;116:405

Synonyms for same clinical syndrome

Cardiac Syndrome – defined as presence of transient left ventricular apical ballooning after ACS in patients with angiographically normal coronary arteries. Iga reported first case. Described in 1990 by Sito et al, as Tako-Tsubo cardiomyopathy.

Named after the octopus trapping pot with a round bottom and narrow neck, which resembles the end systolic left ventriculogramin these patients.

Sporadic cases found around world.

In 2006 , the American Heart association included ABS into its classification of cardiomyopathy as a primary acquired cardiomyopathy.

Circ.2006;113:1807-16.

1-2% of ACS / MI

AHA-732.000 hospital discharges with diagnosis of

AMI /year so annual rate of ABS may be 7.000-14.000

cases.

Worldwide, the incidence of ABS appeared to be on

the rise- recent advances in the work-up of patients with

chest pain.

Am Heart J 2008;155:408-17.

Circulation 2008;118:2754-2762.

Postmenopausal women

88.8% (Gianni et al.14 major studies involving

286 patients), mean age 58-75 yrs- suggest

hormonal predisposition -further investigation to

find out potential mechanisms

Underlying hormonal predisposition-research

Genetic contribution- ( Pison et al. 2 middle-

aged sisters involvement)

Cardiovasc Drug Ther 2008;22:71-77

Eur Heart J 2006;27:1523-9

Chest pain at rest- 50-60%

Dyspnea

Pulmonary edema

Ischemic changes on ECG- diffuse T-wave inversion and

QT prolongation( myocardial stunning)

Elevated cardiac biomarkers

Hypotension

2/3 presented after emotional/physical stressful condition

(“broken heart” syndrom)

Am Heart J 2008;155:408-17.

MC- ST-segment elevation-mimicking STEMI

Typically in precordial leads, but it maybe seen in the

inferior and lateral leads. Non-specific T-wave abnormality,

new bundle branch block and in some cases ECG may be

normal at presentation.

Resolution of ST-segment elevation, development of diffuse

and often deep T-wave inversion that involves most leads.

Resolution occur within 4-6 weeks

Am Heart J 2008;155:408-17

Am. Heart J 2008;155:408-17

Coronary angiography- normal coronary arteries /mild atherosclerosis,

Left ventriculography- hypokinesia, akinesia or even dyskinesia of the mid and or apical segment of LV.

TTE-RW abnormality is beyond the distribution of single coronary artery (30% right ventricle shows similar RWA)

Magnetic resonance- extent of the RWM abnormality and differentiating myocardial infarction and myocarditis.

Circulation . 2008;118:2754-2762.

Classical situation:- a postmenopausal woman

In intensive care unit:-

Mayo clinic criteria-1. Transient hypokinesis, akinesis, or dyskinesis of the left ventricular mid

segments with or without apical involvement; the regional wall motion abnormalities extend beyond a single epicardial vascular distribution; a stressful trigger is often, but not always present.

2. Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture.

3. New electrocardiographic abnormalities (either ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin.

4. Absence of: Pheochromocytoma Myocarditis

American Heart Journal Volume 155, Isssue3, March 2008,408-417

Emotional or physical stress

Sepsis-pathogen induced pro-inflammatory immune response

Critical illness

Subarachnoid hemorrage

Fig. from Am. Heart J 2008;155:408-17

Rare cases precipitated by

1. Hypoglycemia

2. Hyperthyroidism

3. Cocaine

4. Alcohol withdrawal

5. Pneumothorax

6. Subdural hematoma

All these associated with increased sympathetic drive.

Heterogeneous condition, which lacks a disease specific

etiology.

Catecholamine –mediated toxicity- increases in sympathetic

tone following a stressful event and could result in direct

cardio toxicity.

Multi-vessel epicardial coronary artery spasm

Microvascular dysfunction

Spontaneous aborted myocardial infarction

Cardiovasc Drugs Ther 2008; 22:71-77

Myocarditis

A lack of supporting histological and microbiological evidence

Mild interstitial fibrosis and limited mononuclear cellular

infiltration- ABS

Gadolinium-enhanced MRI studies failed to detect regional T2

enhancement, indicating inflammation and necrosis seen in

myocarditis

JACC, 2003;41:737-42.

Elevated circulating catecholamine-( Wittstein et al. 13 ABS and 7 MI),

1) levels remained dramatically raised even after cardiac function was

restored. 2) not every patient with ABS shows elevated catecholamine. 3)

all patients had suffered emotional stress prior to the cardiac event.

Kurisu et al.`s (30pt) six had normal serum nonadrenaline

One review mention 74.3% had elevated nonadrenaline

Disease affecting catecholamine levels (pheocromocytona, subarachnoid

hemorrage) can cause reversible LV dysfunction.

Sepsis and respiratory faillure- increase sympathetic

Anaphalaxis –histamine- adrenal medulla-catecholamine

Wealth of evidence point towards a pathogenic role for catecholamine in

ABS though exact nature remain unclear.

Cardiovasc Drugs Ther 2008;22:71-77Elevated catecholamine levels in ABS is a result of the disease process or is it the cause ???????????

Based on the 201Tl images, myocardial perfusion did not seem to be severely impaired even in

the acute phase, whereas fatty acid metabolism was profoundly depressed in the apical

myocardium in parallel with myocardial contraction abnormalities. The defective uptake seen on

both BMIPP and 201Tl improved within 3 weeks. However, the MIBG images showed that

sympathetic denervation persisted for 1 year after onset, which suggests that the primary cause of

AB cardiomyopathy is a disturbance of the cardiac sympathetic innervations.

Owa et al. serial SPECT scan

Functional sympathetic innervations- 123 I-MIBG

Fatty acid metabolism(C function)- 123 I- BMIPP

Myocardial perfusion- 201 Thallium scan

Sympathetic dysfunction and transiently disturbed cardiac function in the presence of normal

perfusion.

Jpn Circ J 2002;66:712-3.

Contraction-band necrosis is the classic histological finding in

catecholamine excess induced cardiovascular injury; seen in

pheochromocytoma and subarachnoid hemorrhage,

Only one patient of TTS studied by Wittstein et al.

Recently published Inverted TT syndrome case report -shows same

findings

Akashi et al. 7/ 5 biopsies -fatty infiltration-1;mild interstitial fibrosis-1;

small num of mononuclear cells (chronic myocarditis)-2; last patient

shows only adipose tissue

Int. Journal of cardiology 2010 Vol.8:no. 1

TCM: Pathological Insight from a

fatal case

Triphenyl tetrazolium chloride staining

Very strong C4d staining along the microvasculature and in the rare myocytes

with contraction band suggest that there was recent activation of the

complement cascade which is likely secondary to subendocardial ischemia due

to catecholamine surge.

C4d staining of a right ventricular endomyocardial biopsy may be used as

diagnostic tool to better predict the presence of injury??

The Int. Journal of Cardiology vol.8.

Positive C4d staining

Central hypothesis is challenged by the gender discrepancy.

If this is the predominant mechanism, one would expect a similar

incidence in men and women.

In fact, males have a greater adrenergic response to mental stress.

In women, estrogen plays a protective role on the vascular bed from the

adverse effects of catecholamine surge.

So relative deficiency of estrogen after menopause may predispose them to

ABS

A possible animal model of a

‘Tako-Tsubo’ cardiomyopathyUeyama et al.

• Characteristic LV apical ballooning in 8/10 rat subjected to the stress of

remaining immobilized on their back for 30 mins.

• Pre-administration of alfa/beta blockers (but no CCB/NTG), averted

anticipated ventricular dysfunction.

• Anatomical variation in (high) apical adrenergic receptor density may

explain the largely apical involvement.

• Basal myocardium has a somewhat higher norepinephrine content and

greater density of sympathetic nerves than apical.

Circ J 2002; 66: 712–713.

Adrenergic receptor activation is central to the etiology of ABS

The available pathophysiological information indicates that the

apical ballooning syndrome is result of toxic high local

concentration of catecholamine, not coronary artery or microvascular

disease.

Individual differences in the anatomy of cardiac sympathetic

innervation or the distributions of adrenoceptors might result in the

involvement of a variety of left ventricular myocardial segments.

In typical ballooning , high conc. of norepinephrine might evoke

basal hyperkinesia.

Elevated catecholamine level and adrenergic receptor

hypersensitivity is most accepted theory

In absence of significant comorbidities, prognosis is good.

The systolic dysfunction and RWM abnormalities are

transient and resolve completely within days to few weeks

(4-8 week). This is such a uniform finding.

In hospital mortality is very low (1-2%)

Long term survival is similar to that of the general age-

matched population.

Rate of recurrence is not > 10%

Complications are heart failure, ventricular arrhythmias,

LV free wall rupture, mural thrombus formation

JACC 2007; 50:448-52

Presumed to be suffering from an acute coronary syndrome and immediate

appropriate management should follow.

Aspirin, B-blockers and diuretics

Short term anticoagulation to prevent mural thrombus is indicated

B-blocker continued indefinitely due to the chance of a late recurrence

Due to prolonged QT interval leads to arrhythmia- VT- magnesium sulfate (if

cQT>600mSec)

Estrogen treatment – animal model

No specific treatment for left ventricular failure- cardiac function normalized within few weeks.

B-blockers (Sotalol) prolongs QT interval, potentiate adverse effect of high conc. of catecholamine at alfa receptors

ABS has high risk of cardiac rupture, it is still controversial whether to treat with aspirin /heparin

Ann Intern Med 2004;141:858-5

Circulation 2005; 111:388-90

A very small proportion of the population appears to be at

risk for ABS, suggesting a role for genetic predisposition

Whether estrogen replacement therapy will help to reduce

incidence and recurrence of ABS

Investigate the distribution of the adrenergic receptor that

may explain the segmental involvement

Only 30% of cases involve right ventricle

The recurrence rate is low despite the repeated exposure to

stressful events over lifetime

Need to establish a registry for ABS to investigate natural

history and to conduct randomized trials

Take home message

• ABS is not a rare entity. Represents 1-2 % of ACS.

• Prognosis is good, complete recovery within days to weeks, < 10% recurrence.

• Initial management should be directed towards the treatment of MI with continuous ECG monitoring, administration of aspirin, heparin and B-blockers. Consider diuretics and ACE-inhibitors in patients presenting with heart failure .

• Confirmation of diagnosis- particularly important if fibrinolytic therapy is being consider for presumed diagnosis of STEMI.

• Free wall rupture, severe MR, ventricular arrhythmia are rare but fatal complications.

• In the absence of contraindication, chronic B-blocker therapy will aim to reducing likelihood of a recurrent episodes.

• On the basis of rat immobilization model, supplementation of

estrogen in postmenopausal women might be protective.

• Annual clinical follow-up is advisable as natural history of

ABS remains unknown.

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