Transient Stress Cardiomyopathy

BASICS

DESCRIPTION

Transient stress cardiomyopathy (TSC) is a unique cause of reversible left ventricle (LV) dysfunction with a presentation indistinguishable from the acute coronary syndromes (ACS), particularly ST-segment elevation myocardial infarction (MI) (1).
Typically, the patient is a postmenopausal woman who presents with acute chest pain or dyspnea after an identifiable "trigger " (i.e., an acute emotional or physiologic stressor).
First reported by authors from Japan, TSC was known initially as the takotsubo syndrome because the typical LV morphology (i.e., apical ballooning) resembled that of a Japanese octopus trap or takotsubo (2)[B].
Presenting clinical features include the following:
- Chest symptoms and/or dyspnea
- ECG changes, including ST-segment elevations or diffuse T-wave inversions
- Mild elevation in cardiac biomarkers (creatine kinase [CK], troponin)
- Transient wall motion abnormalities that may involve the base, midportion, and/or lateral walls of the LV.
- The apex of the right ventricle (RV) may be affected in up to 25% of cases (3)[B].
Clinical features may vary on a case-by-case basis, and formal diagnostic criteria have not been established.
Authors from the Mayo Clinic have proposed that 3 of the 4 following criteria establish the diagnosis (1)[A]:
- Transient akinesis or dyskinesis of the LV apical and midventricular segments with regional wall motion abnormalities extending beyond a single epicardial vascular distribution
- Absence of obstructive coronary artery disease (CAD) or angiographic evidence of acute plaque rupture
- New ECG abnormalities, either ST-segment elevation or T-wave inversion
- Absence of
  - Recent significant head trauma
  - Intracranial bleeding
  - Pheochromocytoma
  - Obstructive epicardial CAD
  - Myocarditis
  - Hypertrophic cardiomyopathy
Synonym(s): takotsubo cardiomyopathy; apical ballooning syndrome; stress cardiomyopathy; broken heart syndrome; ampulla cardiomyopathy

EPIDEMIOLOGY

Incidence

TSC accounts for a small percentage (1 " 3%) of ACS.
In a recent prospective evaluation of patients admitted to the ICU, as many as 28% had apical ballooning, often in association with sepsis.
Predominant sex: 82 " 100% of cases occur in women.
Predominant age: Mean age of patients is 62 to 75 years.

Prevalence
2.2% of patients presenting to a referral hospital with ST-segment MIs were found to have TSC.

ETIOLOGY AND PATHOPHYSIOLOGY

The exact pathophysiology is not known.
A perturbation in the brain-heart axis, originating in the insular cortex, may be the inciting event (4).
Subsequent overwhelming activation of the sympathetic nervous system initiates a cascade of events, including the following:
- Catecholamine-induced LV dysfunction: "biased agonism " of epinephrine for ²2-adrenergic receptors, located predominantly at the cardiac apex (5)
- Endothelial dysfunction and vasospasm
- Cellular metabolic injury
  - Myocardial norepinephrine release
  - Calcium overload
  - Contraction band necrosis

Genetics
No genetic associations have been described to date.

RISK FACTORS

Female sex
Postmenopausal state
Emotional stress (i.e., argument, death of family member)
Physiologic stress (i.e., acute medical illness)
Chronic neurologic or psychiatric disease (4)

COMMONLY ASSOCIATED CONDITIONS

Death from TSC is rare, and most cases resolve rapidly, within 2 to 3 days. Reported complications include:

Left-sided heart failure
Pulmonary edema
Cardiogenic shock and hemodynamic compromise
Dynamic LV outflow tract gradient complicated by hypotension
Mitral regurgitation
Ventricular arrhythmias
LV thrombus formation
LV free wall rupture
Death (rare, 0 " 8%)

DIAGNOSIS

Because TSC often is indistinguishable from an ACS, it should be treated initially as such:

Activate emergency medical services or report to emergency department.
Oxygen, IV access, and ECG monitoring
Urgent cardiology consultation

HISTORY

In ¢ ; of patients, there is exposure to a "trigger event. "
- Emotional stress: argument, death of family member, divorce, public speaking, and so forth
- Physiologic stress: acute medical condition such as head trauma, asthma attack, seizure, and so forth
In ¢ ; of patients, there is no identifiable trigger (4).
Acute onset of dyspnea or chest pain
Palpitations
Syncope

PHYSICAL EXAM

Exam may be unremarkable or may include any of the following:

Tachypnea
Tachycardia
Hypotension
Jugular venous distension
Bibasilar rales
S3 gallop
Systolic ejection murmur due to dynamic LV outflow tract gradient
Holosystolic murmur of mitral regurgitation

DIFFERENTIAL DIAGNOSIS

Acute ST-segment elevation MI
Pulmonary embolism
Myopericarditis
Pheochromocytoma
Hypertrophic cardiomyopathy
Subarachnoid hemorrhage or stroke

DIAGNOSTIC TESTS & INTERPRETATION

ECG should be done urgently and may show the following:
- Diffuse ST-segment elevations
- Diffuse and often dramatic T-wave inversions
- QTc interval prolongation (6)[B]
- Q waves
Laboratory tests typically reveal a mild elevation in cardiac biomarkers such as
- CK (rarely >500 U/mL)
- Troponin I
- B-type natriuretic peptide (BNP)
- Markers of high filling pressures (e.g., BNP) tend to be higher than markers of necrosis (e.g., CK, troponin).
- TSC can be distinguished from AMI with 95% specificity using a BNP/TnT ratio ≥1,272 (sensitivity 52%) (7)[B].
Chest radiograph
- Cardiomegaly
- Pulmonary edema
Echocardiogram
- Reduced LV systolic function
- Abnormal diastolic function, including evidence of increased filling pressures
- Regional wall motion abnormalities in one of the following patterns:
  - Classic or "takotsubo-type " ballooning of the apex with a hypercontractile base
  - "Reverse takotsubo " : apical hypercontractility with basal akinesis
  - "Midventricular " akinesis with apical and basal hypercontractility
  - Focal or localized akinesis of an isolated segment
- Dynamic intracavitary LV gradient
- Mitral regurgitation
- Variable involvement of the RV
Cardiac MRI
- Reduced LV function
- Wall motion abnormalities as described for transthoracic echocardiography
- Absence of delayed hyperenhancement with gadolinium

Diagnostic Procedures/Other

Because ST-segment elevation MI is the diagnosis of exclusion, patients typically are referred for urgent cardiac catheterization.
Coronary angiography
- Nonocclusive CAD
- Rarely, epicardial coronary spasm
- Endothelial dysfunction as measured by fractional flow reserve or TIMI frame counts
Left-sided heart catheterization: increased LV end-diastolic pressure to a similar degree as AMI (8)[B]
Ventriculography: wall motion abnormalities as described for transthoracic echocardiography
Right-sided heart catheterization
- Increased pulmonary capillary wedge pressure
- Secondary pulmonary hypertension
- Increased right ventricular filling pressures
- Reduced cardiac output or cardiogenic shock (cardiac index <2 and mean arterial pressure [MAP] <60 mm Hg)

Test Interpretation
Characteristic pathologic findings of involved myocardium have not been described.

TREATMENT

Activation of emergency medical services
Advanced cardiac life support therapies as needed
Oxygen
IV access
ECG monitoring

MEDICATION

After diagnostic cardiac catheterization, empirical treatment goals are as follows:

Management of hypotension: differentiation between cardiogenic shock and dynamic LV cavity gradient
Management of increased filling pressures and congestive states
Attenuation of sympathetic drive

First Line

There are no evidence-based treatment recommendations for TSC.
Although ²-blockers are of theoretical benefit, their use has not been associated with improved outcomes in observational cohorts (4)[B].
If there is evidence of left ventricular systolic dysfunction or pulmonary edema, consider the following:
- Furosemide: 20 to 40 mg IV/PO BID as needed to reduce LV filling pressures and dyspnea (9)
- ACE inhibitors or angiotensin receptor blockers: lisinopril 10 to 40 mg/day PO or equivalent or valsartan 80 to 160 mg PO BID have been associated with improved outcomes in observational cohorts (4)[B].

Second Line
Short-term anticoagulation should be considered in patients with severely reduced LV function to prevent LV thrombus formation. Unfractionated heparin 80 U/kg IV bolus followed by 18 U/kg/hr IV or Lovenox 1 mg/kg SC BID.

ISSUES FOR REFERRAL

All patients with TSC generally should be comanaged with cardiology while inpatient and referred to cardiology as an outpatient.

ADDITIONAL THERAPIES

Urgent cardiology consultation and consideration of cardiac catheterization
Hypotension may require the following:
- Vasopressors (e.g., dopamine or Levophed) if there is no LV outflow tract gradient (9)[C]
- Phenylephrine and IV fluids to increase afterload in the presence of an LV outflow tract gradient (9)[C]
- Cardiogenic shock that is not due to an LV outflow tract gradient may require placement of an intra-aortic balloon pump.

INPATIENT CONSIDERATIONS

Admission Criteria/Initial Stabilization

12-lead ECG
Chest radiograph
Laboratory testing
Echocardiography
Patients with TSC usually are admitted for observation because the differential diagnosis includes ACS.

IV Fluids
Normal saline infusion to support BP, if necessary, and no evidence of heart failure
Discharge Criteria
Generally considered after exclusion of ACS and resolution of

Congestive state
Hypotension
Profound impairments of systolic function

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Impairments in systolic function typically resolve in 2 to 3 days but may last as long as 1 month.
Patients should follow up with cardiology and serial echocardiography to document improved LV function.

PROGNOSIS

Prognosis is excellent. Inpatient mortality is rare and ranges from 0% to 8%.
Recurrence is rare; it also has been reported in 0 " 8% of patients.

REFERENCES

11 Bybee KA, Prasad A. Stress-related cardiomyopathy syndromes. Circulation. 2008;118(4):397 " 409.22 Dote K, Sato H, Tateishi H, et al. Myocardial stunning due to simultaneous multivessel coronary spasms: a review of 5 cases [in Japanese]. J Cardiol. 1991;21(2):203 " 214.33 Fitzgibbons TP, Madias C, Seth A, et al. Prevalence and clinical characteristics of right ventricular dysfunction in transient stress cardiomyopathy. Am J Cardiol. 2009;104(1):133 " 136.44 Templin C, Ghadri JR, Diekmann J, et al. Clinical features and outcomes of takotsubo (stress) cardiomyopathy. N Engl J Med. 2015; 373(10): 929 " 935.55 Paur H, Wright PT, Sikkel MB, et al. High levels of circulating epinephrine trigger apical cardiodepression in a ²2-adrenergic receptor/Gi-dependent manner: a new model of takotsubo cardiomyopathy. Circulation. 2012;126(6): 697 " 706.66 Madias C, Fitzgibbons TP, Alsheikh-Ali AA, et al. Acquired long QT syndrome from stress cardiomyopathy is associated with ventricular arrhythmias and torsades de pointes. Heart Rhythm. 2011;8(4):555 " 561.77 Randhawa MS, Dhillon AS, Taylor HC, et al. Diagnostic utility of cardiac biomarkers in discriminating takotsubo cardiomyopathy from acute myocardial infarction. J Card Fail. 2014;20(1):2 " 8.88 Medeiros K, O 'Connor MJ, Baicu CF, et al. Systolic and diastolic mechanics in stress cardiomyopathy. Circulation. 2014;129(16):1659 " 1667.99 Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the International Society for Heart and Lung Transplantation. J Am Coll Cardiol. 2009;53(15):e1 " e90.

CODES

ICD10

I51.81 Takotsubo syndrome

ICD9

429.83 Takotsubo syndrome

SNOMED

441541008 Takotsubo cardiomyopathy

CLINICAL PEARLS

TSC is a cause of reversible LV dysfunction with a clinical presentation indistinguishable from the ACS, particularly ST-segment elevation MI.
Echocardiography may strongly suggest the diagnosis.
Treatment is supportive and should include diuretics and ACE inhibitors in patients with CHF.

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