eMedicine Specialties > Emergency Medicine > Cardiovascular

Cardiomyopathy, Takotsubo

Eric B Tomich, DO, Resident Physician, Department of Emergency Medicine, Madigan Army Medical Center
Emily Merchant, MD, Resident Physician, Chief Resident, Department of Emergency Medicine, Madigan Army Medical Center; Christopher S Kang, MD, Attending Physician, Department of Emergency Medicine, Madigan Army Medical Center; Clinical Assistant Professor, Division of Emergency Medicine, University of Washington; Adjunct Assistant Professor, Uniformed Services University of the Health Sciences; Consulting Staff, Department of Emergency Medicine, Providence St Peter's Hospital; Fellow, Academy of Wilderness Medicine

Updated: Mar 31, 2009

Introduction

Background

Takotsubo cardiomyopathy (TCM) is a transient cardiac syndrome that involves left ventricular apical akinesis and mimics acute coronary syndrome (ACS). It was first described in Japan in 1990 by Sato et al. Patients often present with chest pain, have ST-segment elevation on electrocardiogram, and elevated cardiac enzyme levels consistent with a myocardial infarction.¹ However, when the patient undergoes cardiac angiography, left ventricular apical ballooning is present and there is no significant coronary artery stenosis.

The Japanese word takotsubo translates to "octopus pot," resembling the shape of the left ventricle during systole on imaging studies. Although the exact etiology is still unknown, the syndrome appears to be triggered by a significant emotional or physical stressor.

Example of takotsubo or octopus pot.

The modified Mayo Clinic criteria for diagnosis of takotsubo cardiomyopathy can be applied to a patient at the time of presentation and must contain all 4 aspects:

• Transient hypokinesis, dyskinesis, or akinesis 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.
• Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture
• New electrocardiographic abnormalities (either ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin level
• Absence of pheochromocytoma or myocarditis²

Pathophysiology

The exact etiology of takotsubo cardiomyopathy (TCM) is still unknown, but several theories have been proposed and are being investigated. These include multivessel coronary artery spasm, impaired cardiac microvascular function, impaired myocardial fatty acid metabolism, acute coronary syndrome with reperfusion injury, and endogenous catecholamine-induced myocardial stunning and microinfarction.³  

Normal myocardium utilizes approximately 90% of its energy from fatty acid metabolism at rest and with aerobic activity. During ischemia, this pathway is suppressed and instead glucose is largely utilized, resulting in impaired cardiac function. Patients with takotsubo cardiomyopathy are found to shift toward the glucose pathway despite relatively normal myocardial perfusion and lack of ischemia in left ventricular segments.⁴

The most commonly discussed possible mechanism for takotsubo cardiomyopathy (TCM) is stress-induced catecholamine release, with toxicity to and subsequent stunning of the myocardium. Endomyocardial biopsy of patients with takotsubo cardiomyopathy demonstrates reversible focal myocytolysis, mononuclear infiltrates, and contraction band necrosis. The sympathetic/catecholamine theory is gaining momentum as takotsubo cardiomyopathy has been induced in rats exposed to physical stress and, in some instances, was prevented when pretreated with an alpha- or beta-blocker. Other evidence for this theory has been demonstrated through myocardial imaging studies using catecholamine analogues that evaluate cardiac sympathetic activity. 

Cases of takotsubo cardiomyopathy (TCM) have been reported in the literature following cocaine, methamphetamine, and excessive phenylephrine use.^3,4  Exercise stress testing, which is known to cause increased levels of catecholamines, has resulted in false positives attributable to TCM.⁵ Studies have found that patients with TCM have statistically significant higher levels of serum catecholamines (norepinephrine, epinephrine, and dopamine) than patients with myocardial infarctions.⁶  The apical portions of the left ventricle have the highest concentration of sympathetic innervation found in the heart and may explain why excess catecholamines seem to selectively affect its function.⁴

Frequency

United States

No data are available for incidence or prevalence of takotsubo cardiomyopathy (TCM) in the United States.

International

Studies have reported that 1.7-2.2% of patients who had suspected acute coronary syndrome were subsequently diagnosed with takotsubo cardiomyopathy.^7,8

Mortality/Morbidity

Acute complications occur in approximately 20% of patients, including cardiogenic shock, heart failure, pulmonary edema, dysrhythmias, left ventricular thrombus formation, left ventricular free wall rupture, and death. Estimates of mortality rates have ranged from 1-3.2%.^9,10

Race

Patients are typically Asian or Caucasian. In a literature review of cases in which race was reported 57.2% were Asian, 40% were Caucasian, and 2.8% were other races.¹⁰

Sex

Nearly 90% of reported cases involve postmenopausal women.⁹

Age

Literature reviews report a mean patient age of 67 years, although cases have occurred in children and young adults^3,6

Clinical

History

The clinical presentation of patients ultimately diagnosed with takotsubo cardiomyopathy is usually indistinguishable from that of acute coronary syndrome. 

• The most common presenting symptoms are chest pain and dyspnea, although palpitations, nausea, vomiting, syncope, and rarely, cardiogenic shock have been reported. 
• One of the more unique features of TCM is the association with a preceding emotionally or physically stressful trigger event, occurring in approximately two thirds of patients.
• A recent large systematic review found patients with TCM tend to have a lower incidence of traditional cardiac risk factors such as hypertension, hyperlipidemia, diabetes, smoking, or positive family history for cardiovascular disease.¹¹

Physical

Physical examination findings are nonspecific and often normal, but the patient may have the clinical appearance of having acute coronary syndrome or acute congestive heart failure. 

• Patients may appear anxious and diaphoretic.
• Both tachydysrhythmias and bradydysrhythmias have been reported, but average heart rate in one review was 102 bpm.⁴
• Hypotension can occur from a reduction in stroke volume because of acute left ventricular systolic dysfunction or outflow tract obstruction.
• Murmurs and rales may be present on auscultation in the setting of acute pulmonary edema.

Causes

A significant emotional or physical stressor typically precedes the development of the takotsubo cardiomyopathy (TCM). Stressors include learning of a death of a loved one, bad financial news, legal problems, natural disasters, motor vehicle collisions, exacerbation of a chronic medical illness, newly diagnosed significant medical condition, surgery, intensive care unit stay, and use of or withdrawal from illicit drugs. Recently, TCM has been reported after near drowning episodes.¹²

Differential Diagnoses

Workup

Laboratory Studies

• Cardiac markers, specifically troponin I and T, are elevated in 90% of patients with takotsubo cardiomyopathy (TCM), although to a lesser magnitude than seen in ST-segment elevation myocardial infarction (STEMI). At the time of admission, the mean troponin T level was 0.49 ng/mL (normal <0.01) and the mean troponin I level was 4.2 ng/mL (normal <0.04), while mean peak values during hospitalization for troponin T and troponin I was 0.64 and 8.6 ng/mL, respectively. (For related information on cardiac markers, see Use of Cardiac Markers in the Emergency Department.)
• Brain natriuretic peptide (BNP) level is frequently elevated, especially in those patients demonstrating left heart failure, as it is an indicator of increased left ventricular end-diastolic pressures that result from the stunned myocardium. (For related information on natriuretic peptides, see Natriuretic Peptides in Congestive Heart Failure.)
• Several studies have looked at levels of circulating catecholamines in the acute phase and found that nearly 75% of patients had elevations markedly higher than those with STEMI.^13,14

Imaging Studies

• Chest radiography: Findings are often normal but may demonstrate pulmonary edema.
• Echocardiography: Transthoracic echocardiography provides a quick method of diagnosing wall motion abnormalities typically seen in takotsubo cardiomyopathy, specifically hypokinesis or akinesis of the mid and apical segments of the left ventricle. Perhaps most importantly, these wall motion abnormalities extend beyond the distribution of any single coronary artery. Left ventricular ejection fraction (LVEF) can be estimated by echocardiogram, cardiac MRI, or left ventriculography. Mean LVEF on admission ranged from 20-49%. Echocardiogram is commonly used in following the resolution of the cardiomyopathy and impaired left ventricular (LV) function, with LVEF improving to 59-76% on average, by day 18.

Echocardiogram of a patient with takotsubo cardiomyopathy during systole, which demonstrates apical akinesis. Ejection fraction is 40%.

Echocardiogram of a patient with takotsubo cardiomyopathy during systole nearly 2 months after presenting to the emergency department. Note the improved contractility of the apex. Ejection fraction increased from 40% to 65%.

• Cardiac MRI: In addition to evaluating wall motion abnormalities and LVEF, cardiac MRI has been found to differentiate takotsubo cardiomyopathy, characterized by the absence of delayed gadolinium hyperenhancement, from myocardial infarction and myocarditis in which the opposite occurs.
• Coronary computed tomography (CT) angiography: Although not indicated in the initial evaluation of patients with takotsubo cardiomyopathy, reports are emerging of the use of coronary CT angiography in the subsequent evaluation of patients with takotsubo cardiomyopathy.¹⁵
• Cardiac angiography: The diagnosis of takotsubo cardiomyopathy is typically confirmed in the cardiac catheterization laboratory. In a review of 240 patients diagnosed with takotsubo cardiomyopathy, 211 were found to have completely normal coronary arteries, whereas the remainder had noncritical stenoses. The prevalence of normal coronary arteries by angiography in patients presenting with STEMI ranges from 1-12%. Other etiologies include transient occlusion with spontaneous thrombolysis, vasospasm, and drug induced or withdrawal. Left ventriculography is perhaps the best imaging modality to demonstrate the pathognomonic wall motion and to evaluate LVEF.^11,16

Coronary angiogram of a patient with takotsubo cardiomyopathy demonstrating normal coronary arteries.

Another example of a coronary angiogram of a patient with takotsubo cardiomyopathy demonstrating normal coronary arteries.

Ventriculogram during systole in a patient with takotsubo cardiomyopathy demonstrating apical akinesis.

Ventriculogram during diastole in a patient with takotsubo cardiomyopathy.

Other Tests

• Electrocardiography: ST-segment elevation (67-75%) and T-wave inversion (61%) are the most common abnormalities seen on the initial ECG.  Ninety-five percent of ST-elevations involved the precordial leads and were maximal in leads V₂ -V₃. When compared with patients with STEMI from left anterior descending (LAD) coronary artery occlusion, the amplitude of ST-segment elevations in patients with takotsubo cardiomyopathy was significantly less. An initially normal or nonspecific ECG is seen in 15% of patients with takotsubo cardiomyopathy. Diffuse T-wave inversions tend to occur in the days and weeks following presentation as the ST-segments normalize. There is no reliable way to differentiate takotsubo cardiomyopathy from ST-segment elevation myocardial infarction (STEMI) based solely on the ECG.^11,17

Electrocardiogram of a patient with takotsubo cardiomyopathy demonstrating ST-segment elevation in anterior and inferior leads.

Electrocardiogram of the same patient in previous ECG obtained several days after initial presentation, which demonstrates resolution of ST-segment elevation, and, now, with diffuse T-wave inversion and poor R-wave progression.

Treatment

Prehospital Care

Because takotsubo cardiomyopathy (TCM) mimics acute coronary syndrome (ACS) and no initial ECG finding reliably differentiates takotsubo cardiomyopathy from a ST-segment elevation myocardial infarction (STEMI), prehospital personnel should follow their established protocols for evaluating and transporting patients with chest pain and/or ACS.

Emergency Department Care

Patients should be treated as having acute coronary syndrome (ACS) until proven otherwise. Addressing the airway, breathing, and circulation; establishing intravenous access, and providing supplemental oxygen and cardiac monitoring should take precedence. Testing in the emergency department should include ECG, chest radiography, cardiac biomarker levels, brain natriuretic peptide (BNP) level, and other appropriate laboratory studies. If the patient continues to manifest a clinical picture consistent with acute coronary syndrome, especially a ST-segment elevation myocardial infarction (STEMI), then standard therapies such as aspirin, beta-blockers, nitrates, heparin or enoxaparin, gpIIb/IIIa inhibitors, morphine, and clopidogrel may be indicated. 

Patients in acute congestive heart failure may require diuresis, and patients with cardiogenic shock may require resuscitation with intravenous fluids and inotropic agents. If available, bedside echocardiography could show the characteristic wall motion abnormality. The insertion of an intra-aortic balloon pump has also been reported as being a successful resuscitative intervention, due to left ventricular outflow obstruction that can result from a hyperkinetic basal segment and dyskinetic apex. Fluids and beta-blockers, or calcium channel blockers, are beneficial in this situation, whereas inotropes may exacerbate the problem and should be used with caution. 

Dysrhythmias and cardiopulmonary arrest should be treated using current advanced cardiac life support (ACLS) protocols. Although thrombolytics will not benefit patients with takotsubo cardiomyopathy (TCM), their use should not be withheld when percutaneous coronary intervention (PCI) is not available and patients otherwise meet criteria.^17,18

Consultations

Consultation with a cardiologist is necessary, as coronary angiography is required for the diagnosis of takotsubo cardiomyopathy (TCM). Patients may need to be transferred to a facility with a cardiac catheterization laboratory.^17,18

Medication

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Salicylates

These agents inhibit platelet aggregation.

Aspirin (Anacin, Ascriptin, Bayer Aspirin, Bayer Buffered Aspirin)

Odorless white powdery substance available in 81 mg, 325 mg, and 500 mg for oral use. When exposed to moisture, aspirin hydrolyzes into salicylic acid and acetic acid.
Stronger inhibitor of both prostaglandin synthesis and platelet aggregation than other salicylic acid derivatives. Acetyl group is responsible for inactivation of cyclooxygenase via acetylation. Aspirin is hydrolyzed rapidly in plasma, and elimination follows zero-order pharmacokinetics.
Irreversibly inhibits platelet aggregation by inhibiting platelet cyclooxygenase. This, in turn, inhibits conversion of arachidonic acid to PGI2 (potent vasodilator and inhibitor of platelet activation) and thromboxane A2 (potent vasoconstrictor and platelet aggregate). Platelet inhibition lasts for life of cell (approximately 10 d). May be used in low dose to inhibit platelet aggregation and improve complications of venous stases and thrombosis. Reduces likelihood of myocardial infarction. Also very effective in reducing risk of stroke. Early administration of aspirin in patients with acute myocardial infarction (AMI) may reduce cardiac mortality in first month.

Dosing

Adult

160-324 mg PO or chewed; suppository if patient is unable to take PO medications

Pediatric

Not established

Interactions

Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs; simultaneous administration of other NSAIDs may decrease the cardioprotective and stroke preventive effects

Contraindications

Documented hypersensitivity; liver damage, hypoprothrombinemia, vitamin K deficiency, bleeding disorders, asthma; because of association of aspirin with Reye syndrome, do not use in children (<16 y) with viral infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, with history of blood coagulation defects, or taking anticoagulants

Antianginal Agents

These agents reduce blood pressure.

Nitroglycerin (Deponit, Nitro-Bid, Nitrol, Nitrolingual pumpspray, Nitrostat)

Causes relaxation of the vascular smooth muscle via stimulation of intracellular cyclic guanosine monophosphate production, causing a decrease in blood pressure.

Dosing

Adult

400 mcg SL or spray q5min, repeated up to 3 times
If symptoms persist, administer 5-10 mcg/min IV infusion
Dose should be titrated to reduce MAP by 10%, relieve symptoms, limit adverse effects of hypotension (>30% reduction in MAP or <90 mm Hg systolic), or relieve intolerable headache

Pediatric

Not established

Interactions

Aspirin may increase nitrate serum concentrations; marked symptomatic orthostatic hypotension may occur with coadministration of calcium channel blockers (dose adjustment of either agent may be necessary)

Contraindications

Documented hypersensitivity; severe anemia; shock; postural hypotension; head trauma; closed-angle glaucoma; cerebral hemorrhage

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in coronary artery disease and low systolic blood pressure

Analgesics

Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who experience pain.

Morphine sulfate (Astramorph, Duramorph, MS Contin, MSIR, Oramorph)

DOC for narcotic analgesia because of its reliable and predictable effects, safety profile, and ease of reversibility with naloxone.
Morphine sulfate administered IV may be dosed in a number of ways and is commonly titrated until desired effect obtained.

Dosing

Adult

2 mg IV q5-15min; titrate to symptomatic relief or adverse effects (eg, lethargy, hypotension, respiratory depression)

Pediatric

Not established

Interactions

Phenothiazines may antagonize analgesic effects of opiate agonists; tricyclic antidepressants, MAO inhibitors, and other CNS depressants may potentiate adverse effects of morphine

Contraindications

Documented hypersensitivity; hypotension; potentially compromised airway where establishing rapid airway control would be difficult

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hypotension, respiratory depression, nausea, emesis, constipation, urinary retention, atrial flutter, and other supraventricular tachycardias; has vagolytic action and may increase ventricular response rate

Anticoagulants

These agents inhibit thrombogenesis.

Heparin

Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents recurrence of a clot after spontaneous fibrinolysis.

Dosing

Adult

80 U/kg IV bolus, followed by an infusion of 18 U/kg/h

Pediatric

Not established

Interactions

Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran, dipyridamole, and hydroxychloroquine may increase heparin toxicity

Contraindications

Documented hypersensitivity; subacute bacterial endocarditis; active bleeding; history of heparin-induced thrombocytopenia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In neonates, preservative-free heparin is recommended to avoid possible toxicity (gasping syndrome) by benzyl alcohol, which is used as preservative; caution in severe hypotension and shock; monitor for bleeding in peptic ulcer disease, menstruation, increased capillary permeability, and when giving IM injections

Low Molecular Weight Heparins

These agents inhibit thrombogenesis.

Enoxaparin (Lovenox)

Produced by partial chemical or enzymatic depolymerization of unfractionated heparin (UFH). LMWH differs from UFH by having a higher ratio of antifactor Xa to antifactor IIa compared with UFH. Binds to antithrombin III, enhancing its therapeutic effect. The heparin-antithrombin III complex binds to and inactivates activated factor X (Xa) and factor II (thrombin). Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.
Advantages include intermittent dosing and decreased requirement for monitoring. Heparin anti–factor Xa levels may be obtained if needed to establish adequate dosing. No utility in checking aPTT (drug has wide therapeutic window and aPTT does not correlate with anticoagulant effect). Maximum antifactor Xa and antithrombin activities occur 3-5 h postadministration.
Indicated for treatment of acute ST-segment elevation myocardial infarction (STEMI) managed medically or with subsequent percutaneous coronary intervention (PCI). Also indicated as prophylaxis of ischemic complications caused by unstable angina and non-Q-wave MI.

Dosing

Adult

Treatment regimens for ACS include aspirin (75-325 mg/d) if not contraindicated
Unstable angina or non-Q-wave MI:
1 mg/kg SC q12h
CrCl <30 mL/min: 1 mg/kg SC qd
STEMI
<75 years: 30 mg IV single bolus plus 1 mg/kg SC, then 1 mg/kg SC q12h; not to exceed 100 mg/dose for first 2 SC doses
<75 years and CrCl <30 mL/min: 30 mg IV single bolus plus 1 mg/kg SC, then 1 mg/kg SC qd; not to exceed 100 mg/dose for first 2 SC doses
>75 years: 0.75 mg/kg SC q12h (no initial IV bolus administered); not to exceed 75 mg/dose for first 2 doses
>75 years and CrCl <30 mL/min: 1 mg/kg SC qd (no initial IV bolus administered)
With PCI: If last enoxaparin dose administered >8 h before balloon inflation, administer an additional IV bolus of 0.3 mg/kg
With thrombolytic agent: Give dose specified for age and renal function between 15 min before and 30 min after the start of fibrinolytic therapy

Pediatric

Not established

Interactions

Platelet inhibitors or oral anticoagulants such as dipyridamole, salicylates, aspirin, NSAIDs, sulfinpyrazone, and ticlopidine may increase risk of bleeding

Contraindications

Documented hypersensitivity to heparin or pork products; major bleeding; thrombocytopenia

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Decrease dose if CrCl <30 mL/min; if thromboembolic event occurs despite LMWH prophylaxis, discontinue drug and initiate alternate therapy; elevation of hepatic transaminase levels may occur but is reversible; heparin-associated thrombocytopenia may occur with fractionated low-molecular-weight heparins; 1 mg of protamine sulfate will reverse effect of approximately 1 mg of enoxaparin if significant bleeding complications develop; cases of epidural/spinal hematomas have been reported in adults receiving spinal or epidural anesthesia (holding 2 doses prior to LP or surgery is recommended); obtain hemostasis at puncture site before sheath removal after PCI

Antiarrhythmic Agents

These agents reduce episodes of chest pain.

Esmolol (Brevibloc)

Ultra–short-acting agent that selectively blocks beta1-receptors with little or no effect on beta2-receptor types. Particularly useful in patients with elevated arterial pressure, especially if surgery is planned. Shown to reduce episodes of chest pain and clinical cardiac events compared to placebo. Can be discontinued abruptly if necessary.
Useful in patients at risk for experiencing complications from beta-blockade; particularly those with reactive airway disease, mild-moderate LV dysfunction, and/or peripheral vascular disease. Short half-life of 8 min allows for titration to desired effect and quick discontinuation if needed.

Dosing

Adult

Initial maintenance dose: 0.1 mg/kg/min IV; titrate in increments of 0.05 mg/kg/min q10-15min to a total dose of 0.2 mg/kg/min

Optional loading dose: 0.5 mg/kg slow IV infusion

Pediatric

Not established

Interactions

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels of esmolol, possibly resulting in decreased pharmacologic effect; cardiotoxicity of esmolol may increase when administered concurrently with sparfloxacin, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; toxicity of esmolol increases when administered concurrently with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, and catecholamine-depleting agents

Contraindications

Documented hypersensitivity; uncompensated congestive heart failure, bradycardia, cardiogenic shock, and A-V conduction abnormalities

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Beta-adrenergic blockers may mask signs and symptoms of acute hypoglycemia and clinical signs of hyperthyroidism; symptoms of hyperthyroidism, including thyroid storm, may worsen when medication is abruptly withdrawn; withdraw drug slowly and monitor patient closely

Platelet Aggregation Inhibitors

These agents reduce platelet aggregation.

Abciximab (ReoPro)

Chimeric human-murine monoclonal antibody approved for use in elective/urgent/emergent percutaneous coronary intervention. Binds to receptor with high affinity and reduces platelet aggregation by 80% for up to 48 h following infusion.

Dosing

Adult

0.25 mg/kg IV bolus, followed by 0.125 mcg/kg/min infusion for 12 h; not to exceed 10 mcg/min

Pediatric

Not established

Interactions

Toxicity increases with coadministration of anticoagulants, antiplatelets, and thrombolytics

Contraindications

Documented hypersensitivity; bleeding diathesis, thrombocytopenia (<100,000 cells/m L), recent trauma, intracranial, tumor, severe uncontrolled hypertension; history of vasculitis; cerebrovascular accident within 2 y

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Bleeding complications may occur in patients <75 kg body weight, >65 y, history of gastrointestinal disease, or recently received thrombolytic therapy; severe thrombocytopenia may occur within first 24 h of use

Loop Diuretics

These agents reduce blood pressure.

Furosemide (Lasix)

Loop diuretic that increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. Increases renal blood flow without increasing filtration rate. Onset of action generally is within 1 h. Increases potassium, sodium, calcium, and magnesium excretion.
Dose must be individualized to patient. Depending on response, administer at increments of 20-40 mg, until desired diuresis occurs. When treating infants, titrate with 1-mg/kg/dose increments until a satisfactory effect is achieved.
Diuretics have major clinical uses in managing disorders involving abnormal fluid retention (edema) or in treating hypertension, in which their diuretic action causes decreased blood volume.

Dosing

Adult

40-200 mg IV or PO

Pediatric

Not established; suggested dosing for infants is to titrate in increments of 1 mg/kg/dose until satisfactory effect is achieved

Interactions

Metformin decreases furosemide concentrations; furosemide interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides and furosemide; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently with this medication; increased plasma lithium levels and toxicity are possible when taken concurrently with this medication

Contraindications

Documented hypersensitivity; hepatic coma, anuria, and state of severe electrolyte depletion

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Perform frequent serum electrolyte, CO₂, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter

Thiazide Diuretics

These agents reduce blood pressure.

Hydrochlorothiazide (Esidrix, HydroDIURIL, Microzide)

Inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water as well as potassium and hydrogen ions.

Dosing

Adult

25-100 mg PO qd; not to exceed 200 mg/d

Pediatric

Not established

Interactions

Thiazides may decrease effects of anticoagulants, antigout agents and sulfonylureas; thiazides may increase toxicity of allopurinol, anesthetics, antineoplastics, calcium salts, loop diuretics, lithium, diazoxide, digitalis, amphotericin B, and nondepolarizing muscle relaxants

Contraindications

Documented hypersensitivity; anuria or renal decompensation

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal disease, hepatic disease, gout, diabetes mellitus, and erythematosus

Antihypertensive Agents

These agents reduce blood pressure.

Spironolactone (Aldactone)

For management of edema resulting from excessive aldosterone excretion. Competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions.

Dosing

Adult

25-200 mg/d PO qd or divided bid

Pediatric

Not established

Interactions

May decrease effect of anticoagulants; potassium and potassium-sparing diuretics may increase toxicity of spironolactone

Contraindications

Documented hypersensitivity; anuria, renal failure, or hyperkalemia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal and hepatic impairment

Metoprolol (Lopressor, Toprol XL)

Selective beta1-adrenergic receptor blocker that decreases the automaticity of contractions.
During IV administration, carefully monitor blood pressure, heart rate, and ECG. Goal of treatment is to reduce heart rate to 60-90 beats/min.

Dosing

Adult

5 mg slow IV infusion q5min; to a maximum dose of 15 mg or desired heart rate

Pediatric

Not established

Interactions

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels of metoprolol, possibly resulting in decreased pharmacologic effects; toxicity of metoprolol may increase with coadministration of sparfloxacin, phenothiazines, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; metoprolol may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine

Contraindications

Documented hypersensitivity; uncompensated congestive heart failure, bradycardia, asthma, cardiogenic shock, and A-V conduction abnormalities

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw the drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG

Antiplatelet Agents

These agents inhibit platelet aggregation.

Eptifibatide (Integrilin)

Antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, which reversibly prevents von Willebrand factor, fibrinogen, and other adhesion ligands from binding to the GP IIb/IIIa receptor. Inhibits platelet aggregation. Effects persist over duration of maintenance infusion and are reversed when infusion ends.

Dosing

Adult

Unstable angina: 180 mcg/kg IV bolus, followed by a continuous infusion of 2 mcg/kg/min until discharge or surgery
Patients undergoing PCI: 135 mcg/kg IV bolus; administer before PCI, followed by a continuous infusion of 0.5 mcg/kg/min

Pediatric

Not established

Interactions

When used with heparin and aspirin, an increase in bleeding, compared with using heparin and aspirin alone, can occur; if using concurrently with other drugs that affect hemostasis (eg, warfarin) closely monitor patients

Contraindications

Documented hypersensitivity; severe hypertension (SBP >200 mm Hg); active internal bleeding; history of intracranial hemorrhage; intracranial neoplasm, arteriovenous malformation, or aneurysm; acute pericarditis; bleeding diathesis; trauma or stroke within previous 30 d; platelet count <100,000/mm³; history of thrombocytopenia following exposure to this product
Also contraindicated if serum creatinine level >2 mg/dL (for 180 mcg/kg bolus and 2 mcg/kg/min infusion) or >4 mg/dL (for 135 mcg/kg bolus and 0.5 mcg/kg/min infusion)
History of bleeding diathesis within 30 d; intracranial hemorrhage, a history of hemorrhagic stroke, severe HTN, (systolic BP >200 mm Hg, or diastolic BP >110 mm Hg); major surgical procedure within the past month

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Most common complications encountered during therapy with eptifibatide are bleeding events; caution in patients with a platelet count <150,000/mm³ and in hemorrhagic retinopathy; since agent inhibits platelet aggregation, caution when using concurrently with drugs that affect hemostasis such as thrombolytics, ticlopidine, NSAIDs, warfarin, dipyridamole, and clopidogrel; measure activated clotting time (ACT) and maintain aPTT between 50-70 sec unless a PCI needs to be performed; maintain ACT between 300-350 sec during a PCI; if platelets decrease to <100,000/mm³, additional platelet counts should be performed to exclude possibility of pseudothrombocytopenia; if thrombocytopenia confirmed, discontinue GP IIb/IIIa inhibitors and heparin, and appropriately monitor and treat the condition; to monitor unfractionated heparin, monitor aPTT 6 h after start of heparin infusion and adjust to maintain aPTT higher than twice the baseline level

Tirofiban (Aggrastat)

Nonpeptide antagonist of GP IIb/IIIa receptor. Reversible antagonist of fibrinogen binding. When administered IV, more than 90% of platelet aggregation inhibited.
Approved for use in combination with heparin for patients with unstable angina who are being treated medically and for those undergoing PCI.

Dosing

Adult

0.4 mcg/kg/min IV for 30 min; continue at 0.1 mcg/kg/min
Dose should be halved in patients with severe renal insufficiency (CrCl <30 mL/min)

Pediatric

Not established

Interactions

When used with heparin and aspirin, an increase in bleeding, compared with using heparin and aspirin alone, can occur
If using concurrently with other drugs that affect hemostasis (eg, warfarin), closely monitor patients

Contraindications

Documented hypersensitivity; severe hypertension (SBP >200 mm Hg); active internal bleeding; history of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm; acute pericarditis; bleeding diathesis; trauma or stroke within previous 30 d; platelet count <100,000/mm³; history of thrombocytopenia following exposure to this product
Also contraindicated if serum creatinine level is >2 mg/dL (for 180 mcg/kg bolus and 2 mcg/kg/min infusion) or >4 mg/dL (for 135 mcg/kg bolus and 0.5 mcg/kg/min infusion)
History of bleeding diathesis within 30 d; intracranial hemorrhage; a history of hemorrhagic stroke; severe HTN (systolic BP >200 mm Hg, or diastolic BP >110 mm Hg); major surgical procedure within the past month

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Most common complications in therapy with tirofiban are bleeding events; exercise caution in patients with platelet counts <150,000/mm³ and in patients with hemorrhagic retinopathy
Prior to treating, monitor platelet counts, serum creatinine, hemoglobin, hematocrit, and PT/aPTT within 6 h after loading infusion and at least daily thereafter (more frequently if evidence of significant decline)
Since these agents inhibit platelet aggregation, exercise caution when using concurrently with drugs that affect hemostasis (eg, thrombolytics, ticlopidine, NSAIDs, warfarin, dipyridamole, clopidogrel)
Measure ACT and maintain aPTT between 50-70 seconds unless a PCI needs to be performed; maintain ACT between 300-350 seconds during PCI; if platelet count decreases to fewer than 100,000/mm³, perform additional platelet counts to exclude pseudothrombocytopenia; if thrombocytopenia is confirmed, discontinue GP IIb/IIIa inhibitors and heparin and appropriately monitor and treat the condition
To monitor unfractionated heparin, monitor aPTT 6 h after beginning heparin infusion; adjust to maintain aPTT higher than 2 times baseline
Prior to treating, monitor platelet counts, serum creatinine, hemoglobin, hematocrit, and PT/aPTT within 6 h after loading infusion and at least daily thereafter (more frequently if evidence of significant decline)

Clopidogrel (Plavix)

Selectively inhibits adenosine diphosphate (ADP) binding to platelet receptor and subsequent ADP-mediated activation of glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation.
May have a positive influence on several hemorrhagic parameters and may exert protection against atherosclerosis not only through inhibition of platelet function but also through changes in the hemorrhagic profile.
Shown to decrease cardiovascular death, MI, and stroke in patients with acute coronary syndrome (ie, unstable angina, non-Q-wave MI).

Dosing

Adult

Loading dose: 300 mg PO once
Maintenance: 75 mg PO qd administered with aspirin 75-325 mg/d PO

Pediatric

Not established

Interactions

Coadministration with naproxen associated with increased occult GI blood loss; clopidogrel prolongs bleeding time; safety of coadministration with warfarin not established

Contraindications

Documented hypersensitivity; active pathological bleeding, such as peptic ulcer, or intracranial hemorrhage

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients at increased risk of bleeding from trauma, surgery, or other pathological conditions; caution in patients with lesions with propensity to bleed (eg, ulcers)

Angiotensin-converting Enzyme (ACE) Inhibitors

These agents help control blood pressure.

Lisinopril (Prinivil, Zestril)

Prevents conversion of angiotensin I to angiotensin II (a potent vasoconstrictor), resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

Dosing

Adult

10 mg/d PO qd or divided bid; increase by 5-10 mg/d at 1- to 2-wk intervals; not to exceed 80 mg/d

Pediatric

Not established

Interactions

NSAIDs may reduce hypotensive effects of lisinopril; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases lisinopril levels; probenecid may increase lisinopril levels; the hypotensive effects of ACE inhibitors may be enhanced when given concurrently with diuretics

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal impairment, valvular stenosis, or severe congestive heart failure

Enalapril (Vasotec)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.
Helps control blood pressure and proteinuria. Decreases pulmonary-to-systemic flow ratio in the catheterization laboratory and increases systemic blood flow in patients with relatively low pulmonary vascular resistance. Has favorable clinical effect when administered over a long period. Helps prevent potassium loss in distal tubules. Body conserves potassium; thus, less oral potassium supplementation needed.

Dosing

Adult

2.5-5 mg/d PO (increase as necessary)
Dosing range: 10-40 mg/d PO in 1-2 divided doses
Alternatively, 1.25 mg/dose IV over 5 min q6h

Pediatric

Not established

Interactions

NSAIDs may reduce hypotensive effects of enalapril; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases enalapril levels; probenecid may increase enalapril levels; the hypotensive effects of ACE inhibitors may be enhanced when given concurrently with diuretics

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal impairment, valvular stenosis, or severe congestive heart failure; IV formulation not recommended in managing neonatal hypertension because of risk of acute renal failure and oliguria

Beta-adrenergic Blockers

These agents are used to reduce blood pressure.

Atenolol (Tenormin)

Used to treat hypertension. Selectively blocks beta1-receptors with little or no affect on beta2 types. Beta-adrenergic blocking agents affect blood pressure via multiple mechanisms. Actions include negative chronotropic effect that decreases heart rate at rest and after exercise, negative inotropic effect that decreases cardiac output, reduction of sympathetic outflow from the CNS, and suppression of renin release from the kidneys. Used to improve and preserve hemodynamic status by acting on myocardial contractility, reducing congestion, and decreasing myocardial energy expenditure.
Beta-adrenergic blockers reduce inotropic state of left ventricle, decrease diastolic dysfunction, and increase LV compliance, thereby reducing pressure gradient across LV outflow tract. Decreases myocardial oxygen consumption, thereby reducing myocardial ischemia potential. Decreases heart rate, thus reducing myocardial oxygen consumption and reducing myocardial ischemia potential.
During IV administration, carefully monitor blood pressure, heart rate, and ECG.

Dosing

Adult

25-100 mg/d PO in am or divided bid

Pediatric

0.1-0.3 mg/kg/d PO q12-24h

Interactions

Coadministration with aluminum salts, barbiturates, calcium salts, cholestyramine, NSAIDs, penicillins, and rifampin may decrease effects; haloperidol, hydralazine, loop diuretics, and MAO inhibitors may increase toxicity of atenolol

Contraindications

Documented hypersensitivity; congestive heart failure; pulmonary edema; cardiogenic shock; AV conduction abnormalities; heart block (without a pacemaker)

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Beta-adrenergic blockade may reduce symptoms of acute hypoglycemia and mask signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism and cause thyroid storm; monitor patients closely and withdraw drug slowly; during an IV, carefully monitor BP, heart rate, and ECG

Metoprolol (Lopressor, Toprol XL)

Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor blood pressure, heart rate, and ECG.

Dosing

Adult

100 mg/d PO qd or divided bid/tid initially and increase at 1-wk interval prn to a total of 450 mg/d if necessary

Pediatric

Not established

Interactions

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels of metoprolol, possibly resulting in decreased pharmacologic effects; toxicity of metoprolol may increase with coadministration of sparfloxacin, phenothiazines, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; metoprolol may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine

Contraindications

Documented hypersensitivity; uncompensated congestive heart failure; bradycardia; asthma; cardiogenic shock; AV conduction abnormalities

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw the drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG

Calcium Channel Blockers

These agents improve oxygen delivery to myocardial tissue.

Verapamil (Calan, Calan SR, Covera-HS, Verelan)

During depolarization, inhibits calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium.

Dosing

Adult

240-480 mg/d PO divided tid/qid

Pediatric

Not established

Interactions

Verapamil may increase carbamazepine, digoxin, and cyclosporine levels; coadministration with amiodarone can cause bradycardia and a decrease in cardiac output; when administered concurrently with beta-blockers may increase cardiac depression; cimetidine may increase verapamil levels; verapamil may increase theophylline levels

Contraindications

Documented hypersensitivity; severe CHF, sick sinus syndrome or second- or third-degree AV block, and hypotension (<90 mm Hg systolic)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Depresses impulse formation, AV block, negative inotropism, and vasodilation, which can result in hypotension, shock, pulmonary edema, and death; hepatocellular injury may occur; transient elevations of transaminase levels with or without concomitant elevations in alkaline phosphatase and bilirubin levels have occurred (elevations have been transient and may disappear with continued verapamil treatment), monitor liver function; IV administration discouraged in neonates and young infants due to severe apnea, bradycardia, hypotension, and cardiac arrest periodically

Diltiazem (Cardizem CD, Cardizem LA, Dilacor, Tiamate, Tiazac)

During depolarization, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. Serum calcium levels remain unchanged. The resultant decrease in intracellular calcium inhibits the contractile processes of myocardial smooth muscle cells, resulting in dilation of the coronary and systemic arteries and improved oxygen delivery to the myocardial tissue.

Decreases conduction velocity in AV node. Also increases refractory period via blockade of calcium influx. This, in turn, stops reentrant phenomenon.

Decreases myocardial oxygen demand by reducing peripheral vascular resistance, reducing heart rate by slowing conduction through SA and AV nodes, and reducing LV inotropy. Slows AV nodal conduction time and prolongs AV nodal refractory period, which may convert SVT or slow the rate in atrial fibrillation. Also has vasodilator activity but may be less potent than other agents. Total peripheral resistance, systemic blood pressure, and afterload are decreased.

Calcium channel blockers provide control of hypertension associated with less impairment of function of the ischemic kidney. Calcium channel blockers may have beneficial long-term effects, but this remains uncertain.

Dosing

Adult

Cardizem SR: 60-120 mg PO bid
Cardizem CD: Hypertension: 180-240 mg PO qd
Cardizem LA: Hypertension: 120-540 mg PO qd
Dilacor: Hypertension: 180-240 mg PO qd
Angina: 120 mg/d PO; titrate slowly over 7-14 d up to 480 mg/d prn (do not exceed 540 mg/d)

Pediatric

Not established

Interactions

May increase carbamazepine, digoxin, and cyclosporine, theophylline levels; when administered with amiodarone, may cause bradycardia and a decrease in cardiac output; when given with beta-blockers may increase cardiac depression; cimetidine may increase diltiazem levels

Contraindications

Documented hypersensitivity; severe CHF, sick sinus syndrome, second- or third-degree AV block, and hypotension (<90 mm Hg systolic)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in impaired renal or hepatic function; may increase LFT levels, and hepatic injury may occur

Amlodipine (Norvasc)

Generally regarded as a dihydropyridine, although experimental evidence suggests that it also may bind to the nondihydropyridine binding sites. Appropriate for the prophylaxis of variant angina. Has antianginal and antihypertensive effects. Blocks the postexcitation release of calcium ions into cardiac and vascular smooth muscle, thereby inhibiting the activation of ATPase on myofibril contraction. The overall effect is reduced intracellular calcium levels in cardiac and smooth muscle cells of the coronary and peripheral vasculature, resulting in dilatation of coronary and peripheral arteries. Also increases myocardial oxygen delivery in patients with vasospastic angina. May also potentiate ACE inhibitor effects.
During depolarization, inhibits calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium. Benefits nonpregnant patients with systolic dysfunction, hypertension, or arrhythmias. Can be used during pregnancy if clinically indicated. Has a substantially longer half-life than nifedipine and diltiazem and is administered qd.

Dosing

Adult

2.5-5 mg PO qd; not to exceed 10 mg/d

Pediatric

Not established

Interactions

Fentanyl and alcohol may increase hypotensive effects; calcium channel blockers may increase cyclosporine levels; H2 blockers (cimetidine), erythromycin, nafcillin, and azole antifungals may increase toxicity (avoid combination or monitor closely); carbamazepine may reduce bioavailability (avoid this combination); rifampin may decrease levels (monitor and adjust dose of calcium channel blocker)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adjust dose in renal/hepatic impairment; may cause lower extremity edema; allergic hepatitis has occurred but is rare

Follow-up

Further Inpatient Care

Patients with takotsubo cardiomyopathy (TCM) will require admission to the appropriate cardiology service. Treatment options are largely empirical and supportive; however, when hemodynamics permit, beta-blockers seem to be helpful. Serial imaging studies may be necessary. Patients who are found to have left ventricular thrombus, which occurs in 5% of patients with TCM, require anticoagulation.¹⁹

Further Outpatient Care

Close follow-up care with a cardiologist in the weeks after diagnosis is recommended for these patients to ensure resolution of the cardiomyopathy, usually with serial echocardiograms. Thereafter, annual clinical follow-up is advised because the long-term effects and natural history of takotsubo cardiomyopathy are unknown.^16,18

Inpatient & Outpatient Medications

Currently, no randomized controlled trials have been performed to evaluate medical therapies for takotsubo cardiomyopathy; however, it is common practice to prescribe angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, at least until left ventricular function is restored. Beta-blockers are also indicated and may be useful in the long term. Other standard outpatient post-STEMI medications such as statins, aspirin, and clopidogrel are of unknown benefit. Patients with known left ventricular thrombus should be anticoagulated until LV function normalizes and thrombus is no longer present on echocardiogram.¹⁹

Transfer

Patients may need to be transferred to a facility with a cardiologist and cardiac catheterization laboratory.^13,14

Deterrence/Prevention

Chronic beta-blocker therapy may reduce the likelihood of recurrent episodes.¹⁶

Complications

Complications occur in 20% of takotsubo cardiomyopathy cases and include the following:

• 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
• Death^20,17

Prognosis

Prognosis is excellent, with nearly 95% of patients experiencing complete recovery within 4-8 weeks. Recurrence rate varies but is estimated at 3%.^11,16

Miscellaneous

Medicolegal Pitfalls

Physicians should be aware of the presentation of takotsubo cardiomyopathy (TCM) because as described above, chest pain after a recent stressor is not necessarily due to anxiety. The chest pain may be more complicated and deteriorate into dysrhythmias and/or shock. Patients with takotsubo cardiomyopathy do not usually have cardiac risk factors, but their pain should be taken seriously. Also, patients may present to the ED after a natural disaster, and providers should be aware that the incidence of takotsubo cardiomyopathy might increase soon afterward. These patients should be treated in the emergency department as having acute coronary syndrome (ACS), given supportive treatment, and undergo subsequent cardiology evaluation.

Special Concerns

Recently, atypical forms of takotsubo cardiomyopathy have been described with varying wall motion abnormalities including right ventricular and basal/midventricular akinesia. Clinically, these patients tend to present similarly to the classic form.¹¹

Multimedia

Media file 1: Example of takotsubo or octopus pot.

Media file 2: Electrocardiogram of a patient with takotsubo cardiomyopathy demonstrating ST-segment elevation in anterior and inferior leads.

Media file 3: Electrocardiogram of the same patient in previous ECG obtained several days after initial presentation, which demonstrates resolution of ST-segment elevation, and, now, with diffuse T-wave inversion and poor R-wave progression.

Media file 4: Coronary angiogram of a patient with takotsubo cardiomyopathy demonstrating normal coronary arteries.

Media file 5: Another example of a coronary angiogram of a patient with takotsubo cardiomyopathy demonstrating normal coronary arteries.

Media file 6: Ventriculogram during systole in a patient with takotsubo cardiomyopathy demonstrating apical akinesis.

Media file 7: Ventriculogram during diastole in a patient with takotsubo cardiomyopathy.

Media file 8: Echocardiogram of a patient with takotsubo cardiomyopathy during diastole several days after presenting to the emergency department.

Media file 9: Echocardiogram of a patient with takotsubo cardiomyopathy during systole, which demonstrates apical akinesis. Ejection fraction is 40%.

Media file 10: Echocardiogram of a patient with takotsubo cardiomyopathy during systole nearly 2 months after presenting to the emergency department. Note the improved contractility of the apex. Ejection fraction increased from 40% to 65%.

Media file 11: Echocardiogram of a patient with takotsubo cardiomyopathy during diastole approximately 2 months after presenting to the emergency department.

Media file 12: Echocardiogram focused on left ventricle of a patient with takotsubo cardiomyopathy during diastole.

Media file 13: Echocardiogram focusing on left ventricle of a patient with takotsubo cardiomyopathy during systole. Note apical akinesis.

Media file 14: Echocardiogram focusing on left ventricle of a patient with takotsubo cardiomyopathy during systole approximately 2 months after presenting to the emergency department. Note improved apical contraction.

Media file 15: Echocardiogram focusing on left ventricle of a patient with takotsubo cardiomyopathy during diastole approximately 2 months after presenting to the emergency department.

References

1. Sato H, Tateishi H, Uchida T, et al. Kodama K, Haze K, Hon M, eds. Clinical Aspect of Myocardial Injury: From Ischaemia to Heart Failure. Tokyo: Kagakuhyouronsya; 1990:56-64.

2. Kawai S, Kitabatake A, Tomoike H. Guidelines for diagnosis of takotsubo (ampulla) cardiomyopathy. Circ J. Jun 2007;71(6):990-2. [Medline].

3. Afonso L, Bachour K, Awad K, Sandidge G. Takotsubo cardiomyopathy: pathogenetic insights and myocardial perfusion kinetics using myocardial contrast echocardiography. Eur J Echocardiogr. Nov 2008;9(6):849-54. [Medline].

4. Dorfman TA, Iskandrian AE. Takotsubo cardiomyopathy: State-of-the-art review. J Nucl Cardiol. Jan-Feb 2009;16(1):122-34. [Medline].

5. Dhoble A, Abdelmoneim SS, Bernier M, Oh JK, Mulvagh SL. Transient left ventricular apical ballooning and exercise induced hypertension during treadmill exercise testing: is there a common hypersympathetic mechanism?. Cardiovasc Ultrasound. Jul 18 2008;6:37. [Medline].

6. Buchholz S, Rudan G. Tako-tsubo syndrome on the rise: a review of the current literature. Postgrad Med J. Apr 2007;83(978):261-4. [Medline].

7. Bybee KA, Prasad A, Barsness GW, et al. Clinical characteristics and thrombolysis in myocardial infarction frame counts in women with transient left ventricular apical ballooning syndrome. Am J Cardiol. Aug 1 2004;94(3):343-6. [Medline].

8. Ito K, Sugihara H, Katoh S, Azuma A, Nakagawa M. Assessment of Takotsubo (ampulla) cardiomyopathy using 99mTc-tetrofosmin myocardial SPECT--comparison with acute coronary syndrome. Ann Nucl Med. Apr 2003;17(2):115-22. [Medline].

9. Gianni M, Dentali F, Grandi AM, Sumner G, Hiralal R, Lonn E. Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review. Eur Heart J. Jul 2006;27(13):1523-9. [Medline].

10. Donohue D, Movahed MR. Clinical characteristics, demographics and prognosis of transient left ventricular apical ballooning syndrome. Heart Fail Rev. Dec 2005;10(4):311-6. [Medline].

11. Pilgrim TM, Wyss TR. Takotsubo cardiomyopathy or transient left ventricular apical ballooning syndrome: A systematic review. Int J Cardiol. Mar 14 2008;124(3):283-92. [Medline].

12. Citro R, Previtali M, Bossone E. Tako-tsubo cardiomyopathy and drowning syndrome: is there a link?. Chest. Aug 2008;134(2):469. [Medline].

13. Sharkey SW, Lesser JR, Menon M, Parpart M, Maron MS, Maron BJ. Spectrum and significance of electrocardiographic patterns, troponin levels, and thrombolysis in myocardial infarction frame count in patients with stress (tako-tsubo) cardiomyopathy and comparison to those in patients with ST-elevation anterior wall myocardial infarction. Am J Cardiol. Jun 15 2008;101(12):1723-8. [Medline].

14. Kolkebeck TE, Cotant CL, Krasuski RA. Takotsubo cardiomyopathy: an unusual syndrome mimicking an ST-elevation myocardial infarction. Am J Emerg Med. Jan 2007;25(1):92-5. [Medline].

15. Scheffel H, Stolzmann P, Karlo C, et al. Tako-tsubo phenomenon: dual-source computed tomography and conventional coronary angiography. Cardiovasc Intervent Radiol. Jan-Feb 2008;31(1):226-7. [Medline].

16. Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J. Mar 2008;155(3):408-17. [Medline].

17. Merchant EE, Johnson SW, Nguyen P, Kang C, Mallon WK. Takotsubo cardiomyopathy: a case series and review of the literature. WestJEM. 2008;9:104-11.

18. Sealove BA, Tiyyagura S, Fuster V. Takotsubo cardiomyopathy. J Gen Intern Med. Nov 2008;23(11):1904-8. [Medline].

19. Kurisu S, Inoue I, Kawagoe T, Ishihara M, Shimatani Y, Nakama Y. Incidence and treatment of left ventricular apical thrombosis in Tako-tsubo cardiomyopathy. Int J Cardiol. Feb 2 2009;[Medline].

20. Bybee KA, Kara T, Prasad A, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med. Dec 7 2004;141(11):858-65. [Medline].

21. Khallafi H, Chacko V, Varveralis N, Elmi F. "Broken heart syndrome": catecholamine surge or aborted myocardial infarction?. J Invasive Cardiol. Jan 2008;20(1):E9-13. [Medline].

22. Terefe YG, Niraj A, Pradhan J, Kondur A, Afonso L. Myocardial infarction with angiographically normal coronary arteries in the contemporary era. Coron Artery Dis. Dec 2007;18(8):621-6. [Medline].

Keywords

takotsubo cardiomyopathy, cardiac syndrome, myocardial infarction, TCM, broken heart syndrome, stress-induced cardiomyopathy, transient left ventricular apical ballooning syndrome, ampulla cardiomyopathy, acute coronary syndrome, ACS, symptoms, treatment, causes

Contributor Information and Disclosures

Author

Eric B Tomich, DO, Resident Physician, Department of Emergency Medicine, Madigan Army Medical Center
Eric B Tomich, DO is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Osteopathic Association, and Emergency Medicine Residents Association
Disclosure: Nothing to disclose.

Coauthor(s)

Emily Merchant, MD, Resident Physician, Chief Resident, Department of Emergency Medicine, Madigan Army Medical Center
Emily Merchant, MD is a member of the following medical societies: American College of Emergency Physicians, Emergency Medicine Residents Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Christopher S Kang, MD, Attending Physician, Department of Emergency Medicine, Madigan Army Medical Center; Clinical Assistant Professor, Division of Emergency Medicine, University of Washington; Adjunct Assistant Professor, Uniformed Services University of the Health Sciences; Consulting Staff, Department of Emergency Medicine, Providence St Peter's Hospital; Fellow, Academy of Wilderness Medicine
Christopher S Kang, MD is a member of the following medical societies: American College of Emergency Physicians, Society of US Army Flight Surgeons, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Edward Bessman, MD, Chairman, Department of Emergency Medicine, John Hopkins Bayview Medical Center; Assistant Professor, Department of Emergency Medicine, Johns Hopkins University
Edward Bessman, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Gary Setnik, MD, Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Division of Emergency Medicine, Harvard Medical School
Gary Setnik, MD is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society for Academic Emergency Medicine
Disclosure: SironaHealth Salary Management position; South Middlesex EMS Consortium Salary Management position

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

David FM Brown, MD, Assistant Professor, Division of Emergency Medicine, Harvard Medical School; Vice Chair, Department of Emergency Medicine, Massachusetts General Hospital
David FM Brown, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

The opinions or assertions contained herein are the private views of the authors and not to be construed as official or reflecting the views of the Department of the Army, the Department of Defense, or the US Government.

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