TAKOTSUBO MEDSCAPE

Takotsubo cardiomyopathy (TCM) is a transient cardiac syndrome that involves

left ventricular apical akinesis and mimics acute coronary syndrome. 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. (See the images below.) [1, 2]
However, when the patient undergoes cardiac angiography, left ventricular
apical ballooning is present and there is no significant coronary artery stenosis.
(See Clinical and Workup.)[3]

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

Electrocardiogram from the

same patient examined in the previous ECG, obtained several days after initial
presentation. This demonstrates resolution of ST-segment elevation, and now
with diffuse T-wave inversion and poor R-wave progression.
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. [4] (See Etiology.)
The modified Mayo Clinic criteria for diagnosis of TCM [5] can be applied to a
patient at the time of presentation and must contain all 4 aspects (see Workup):

Transient hypokinesis, dyskinesis, or akinesis of the left ventricular

midsegments, with or without apical involvement; the regional wall-motion
abnormalities extend beyond a single epicardial vascular distribution, and
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 myocarditis

[5]

The exact etiology of takotsubo cardiomyopathy (TCM) is still unknown, but several theories
have been proposed and are being investigated.[6] 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.[7, 8]
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 TCM are
found to shift toward the glucose pathway despite relatively normal myocardial perfusion and
lack of ischemia in left ventricular segments.[9]
The most commonly discussed possible mechanism for TCM is stress-induced catecholamine
release, with toxicity to and subsequent stunning of the myocardium.[4] Endomyocardial
biopsy of patients with TCM demonstrates reversible focal myocytolysis, mononuclear
infiltrates, and contraction band necrosis. The sympathetic/catecholamine theory is gaining
momentum, because TCM was induced in rats exposed to physical stress and, in some
instances, was prevented by pretreatment with an alpha blocker or beta blocker. Other
evidence for this theory has been demonstrated through myocardial imaging studies using
catecholamine analogues, that evaluated cardiac sympathetic activity.
Some authors have proposed a unifying hypothesis stating that in susceptible individuals,
notably women, neurohormonal stimulation results in acute myocardial dysfunction, as
reflected by the characteristic left ventricular wall-motion abnormality of TCM. Whether
triggered by multivessel spasm, thrombosis, epicardial vessel occlusion, or direct myocardial
toxicity remains to be seen. They point out that the wall-motion abnormality of TCM can be
seen in other conditions, including those with certain left anterior descending (LAD) lesions,
[10]
making wall motion alone insufficient for the diagnosis of TCM.[11]
Cases of TCM have been reported in the literature following cocaine, methamphetamine, and
excessive phenylephrine use.[7, 9] Exercise stress testing, which is known to cause increased
levels of catecholamines, has resulted in false positives attributable to TCM.[12] Studies have
found that patients with TCM have, by a statistically significant margin, higher levels of
serum catecholamines (norepinephrine, epinephrine, and dopamine) than do patients with
myocardial infarctions.[13] 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.[9]

Risk factors
A significant emotional or physical stressor or neurologic injury typically precedes the
development of the TCM.[4] 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; a newly diagnosed, significant medical condition; surgery; an intensive care
unit stay; and the use of or withdrawal from illicit drugs. TCM has also been reported after
near-drowning episodes.[14]
Seizures may also trigger TCM, but it is rare for TCM to result in sudden unexpected death in
epilepsy (SUDEP).[15]

In a systematic review of 104 cases of TCM (1965-2013), investigators noted that young
patients with TCM were more likely to be female, and physical stress rather than mental
stress was more likely to exacerbate TCM.[16, 17] The clinical presentation of TCM in this
patient population was similar to that of other cardiac diseases (eg, coronary heart disease)
but could be differentiated from them with the use of echocardiography in conjunction with
ventriculography.[16]
Similarly, The International Takotsubo Registry reported that patients with TCM were more
likely to be female (89.8%) and that physical triggers (36%) were more common than
emotional triggers (27.7%), although over one quarter (28.5%) had no clear triggers, as
compared to patients with acute coronary syndrome (ACS).[17] Patients with TCM also had
higher rates of neurologic or psychiatric disorders and significantly lower left ventricular
ejection fraction (LVEF). Both groups (TCM and ACS) had similar rates of severe inpatient
complications (eg, shock, death), with the following as independent predictors of such
complications: physical triggers, acute neurologic/psychiatric diseases, elevated troponin
levels, and low LVEF.[17]
Studies reported that 1.7-2.2% of patients who had suspected acute coronary syndrome were
subsequently diagnosed with takotsubo cardiomyopathy (TCM).[18, 19] 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.[20]
Literature reviews report a mean patient age of 67 years, although cases of TCM have
occurred in children and young adults[7, 13] Nearly 90% of reported cases involve
postmenopausal women.[21]
The prognosis in takotsubo cardiomyopathy (TCM) is typically excellent, with nearly 95% of
patients experiencing complete recovery within 4-8 weeks.[22, 23] A study by Singh et al
indicated that the annual recurrence rate is approximately 1.5% but that the frequency of
ongoing symptoms is greater.[24] Estimates of mortality rates have ranged from 1-3.2%.[20, 21]
Complications occur in 20% of TCM cases, particularly in the early stage,[2] 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 [25, 26]

The clinical presentation of patients ultimately diagnosed with takotsubo cardiomyopathy

(TCM) 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 its association with a preceding emotionally or
physically stressful trigger event, occurring in approximately two thirds of patients. Unlike
acute coronary syndrome, in which peak occurrence is during the morning hours, TCM
events are most prevalent in the afternoon, when stressful triggers are more likely to take
place.[27]
A 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.[22]
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. Tachydysrhythmias and bradydysrhythmias
have been reported, but the average heart rate in one review was 102 bpm.[9]
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.
Diagnostic Considerations
Physicians should be aware of the presentation of takotsubo cardiomyopathy (TCM), because
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 TCM do not usually have cardiac risk factors, but their pain should be taken
seriously. Also, patients may present to the emergency department after a natural disaster, and
providers should be aware that the incidence of TCM 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.[28]
TCM should also be a consideration in young patients who present with symptoms similar to
those of coronary heart disease to avoid potentially unnecessary invasive interventions (eg,
coronary artery stent placement).[16]
Atypical forms of TCM 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.[22]
Conditions to consider in the differential diagnosis of TCM include the following:

Esophageal spasm
Gastroesophageal reflux disease

Myocardial infarction

Myocardial ischemia

Myocarditis

Acute pericarditis

Pneumothorax

Cardiogenic pulmonary edema

Pulmonary embolism

Unstable angina

Differential Diagnoses

Acute Coronary Syndrome

Angina Pectoris

Aortic Dissection

Boerhaave Syndrome

Cardiac Tamponade

Cardiogenic Shock

Cocaine-Related Cardiomyopathy

Coronary Artery Vasospasm

Dilated Cardiomyopathy

Hypertrophic Cardiomyopathy

Cardiac markers, specifically troponin I and T, are elevated in 90% of patients with takotsubo
cardiomyopathy (TCM), although to a lesser magnitude than is seen in ST-segment elevation
myocardial infarction (STEMI). The brain natriuretic peptide level is also frequently elevated.
As with any patient in whom acute coronary syndrome is suspected, electrocardiography
should be the initial test obtained soon after presentation to the emergency department.
Transthoracic echocardiography provides a quick method of diagnosing wall motion
abnormalities typically seen in TCM, specifically hypokinesis or akinesis of the midsegment
and apical segment of the left ventricle. The diagnosis of TCM is typically confirmed with
cardiac angiography.
Laboratory Studies

At the time of admission, the mean troponin T level has been found to be 0.49 ng/mL (normal
< 0.01) and the mean troponin I level has been reported as 4.2 ng/mL (normal < 0.04), in
patients with takotsubo cardiomyopathy (TCM), while mean peak values during
hospitalization for troponin T and troponin I have been demonstrated to be 0.64 and 8.6
ng/mL, respectively.
As mentioned, the brain natriuretic peptide level is also 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.
Several studies looked at levels of circulating catecholamines in the acute phase and found
that nearly 75% of patients had elevations markedly higher than did patients with ST-segment
elevation myocardial infarction (STEMI).[29, 30]

Echocardiography
As previously stated, transthoracic echocardiography provides a quick method of diagnosing
wall-motion abnormalities typically seen in takotsubo cardiomyopathy (TCM),[31] specifically
hypokinesis or akinesis of the midsegment and apical segment of the left ventricle. Perhaps
most importantly, these wall motion abnormalities extend beyond the distribution of any
single coronary artery.
The left ventricular ejection fraction (LVEF) can be estimated by echocardiogram, cardiac
magnetic resonance imaging (MRI), or left ventriculography. Mean LVEF on admission has
been found to range from 20-49%.
Echocardiography is commonly used in following the resolution of the cardiomyopathy and
impaired left ventricular function, with LVEF improving to 59-76% on average, by day 18.
(See the images below.)

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

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%.

Echocardiogram of a patient
with takotsubo cardiomyopathy during diastole, approximately 2 months after
presenting to the emergency department.

Echocardiogram focused on
left ventricle of a patient with takotsubo cardiomyopathy during diastole.

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

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.

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

The diagnosis of takotsubo cardiomyopathy (TCM) is typically confirmed in the

cardiac catheterization laboratory. In a review of 240 patients diagnosed with
TCM, 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 ST-segment elevation myocardial
infarction (STEMI) ranges from 1% to 12%. Aside from TCM, this phenomenon
may be explained by transient vessel occlusion with spontaneous thrombolysis,
by vasospasm, or it may be drug related.
Left ventriculography is perhaps the best imaging modality to demonstrate the
pathognomonic wall motion and to evaluate left ventricular ejection fraction
(LVEF).[22, 23] (See the images below.)

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

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.
As with any patient in whom acute coronary syndrome is suspected,
electrocardiograpy (ECG) should be the initial test obtained soon after
presentation to the emergency department. 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 have been found to involve the
precordial leads and to be maximal in leads V2 -V3. When compared with patients
with ST-segment elevation myocardial infarction (STEMI) from left anterior

descending (LAD) coronary artery occlusion, the amplitude of ST-segment

elevations in patients with takotsubo cardiomyopathy (TCM) was significantly
less. (See the images below.)

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

Electrocardiogram from the

same patient examined in the previous ECG, obtained several days after initial
presentation. This demonstrates resolution of ST-segment elevation, and now
with diffuse T-wave inversion and poor R-wave progression.
An initially normal or nonspecific ECG finding is seen in 15% of patients with
TCM. Diffuse T-wave inversions tend to occur in the days and weeks following
presentation as the ST-segments normalize. No reliable way to differentiate TCM
from STEMI is possible based solely on ECG findings. [22, 26]
In a retrospective study of 33 patients with TCM, the authors proposed ECG
criteria to distinguish TCM from anterior acute myocardial infarction (AMI) in
those who presented within 6 hours of symptom onset. The combination of
absent abnormal Q-waves, absent reciprocal changes, lack of ST-segment
elevation in lead V1, and presence of ST-segment elevation in lead aVR had more
than 91% sensitivity and 96% specificity for TCM. [32] (See the images below.)
Other Imaging Techniques
Chest radiographs in takotsubo cardiomyopathy (TCM) are often normal, but they
may demonstrate pulmonary edema.
Cardiac magnetic resonance imaging (MRI) is increasingly being used as a
diagnostic modality that is uniquely suited for establishing the diagnosis of TCM
by accurately visualizing regional wall motion abnormalities, quantifying
ventricular function, and identifying reversible injury to the myocardium by the
presence of edema/inflammation and the absence of necrosis/fibrosis. [33, 34]
In addition to evaluating wall-motion abnormalities and left ventricular ejection
fraction (LVEF), cardiac magnetic resonance imaging (MRI) has been found to
differentiate TCM, characterized by the absence of delayed gadolinium
hyperenhancement, from myocardial infarction and myocarditis, in which the
opposite occurs.

Although not indicated in the initial evaluation of patients with TCM, reports are
emerging of the use of coronary computed tomography (CT) angiography in the
subsequent evaluation of patients with the disorder. [35]
Approach Considerations
Prehospital care
Because takotsubo cardiomyopathy (TCM) mimics acute coronary syndrome and
no initial ECG finding reliably differentiates TCM from STEMI, prehospital
personnel should follow their established protocols for evaluating and
transporting patients with chest pain and/or acute coronary syndrome.
Inpatient care
Patients with 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. [36]
Outpatient care
Close follow-up care with a cardiologist in the weeks after diagnosis is
recommended for patients with TCM 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 TCM are unknown.
[23, 37]

Consultations and transfer

Consultation with a cardiologist is necessary, as coronary angiography is
required for the diagnosis of TCM. Patients may need to be transferred to a
facility with a cardiologist and a cardiac catheterization laboratory. [26, 29, 30, 37]
Emergency Department Care
Patients should be treated as having acute coronary syndrome 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
electrocardiography, chest radiography, cardiac biomarker levels, brain
natriuretic peptide level, and other appropriate laboratory studies.
If the patient continues to manifest a clinical picture consistent with acute
coronary syndrome, especially STEMI, then standard therapies, such as the
following, may be indicated:

Aspirin

Beta blockers

Nitrates

Heparin or enoxaparin

Platelet glycogen (GP) IIb/IIIa inhibitors

Morphine

Clopidogrel

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.[26, 37]
Medication Summary
Currently, no randomized controlled trials have been performed to evaluate
medical therapies for takotsubo cardiomyopathy (TCM); however, it is common
practice to prescribe angiotensin-converting enzyme (ACE) inhibitors or
angiotensin receptor blockers (ARBs), at least until left ventricular function is
restored. Beta blockers are also indicated and may be useful in the long term.
However, a review study and meta-analysis by Singh et al suggested that while
ACE inhibitors and ARBs may reduce the recurrence rate of TCM, beta blockers
may not.[24]
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 left
ventricular function normalizes and thrombus is no longer present on
echocardiogram.[36] Chronic beta-blocker therapy may reduce the likelihood of
recurrent episodes.[23]
Nitroglycerin topical (Nitro-Bid, Nitrolingual pumpspray, Nitrostat,
Nitro-Dur)
Nitroglycerin causes relaxation of the vascular smooth muscle via stimulation of
intracellular cyclic guanosine monophosphate production, causing a decrease in
blood pressure
Analgesics
Class Summary
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, Oramorph SR,

Avinza)
This is the drug of choice for narcotic analgesia because of its reliable and
predictable effects, safety profile, and ease of reversibility with naloxone.
Morphine sulfate administered intravenously may be dosed in a number of ways
and is commonly titrated until the desired effect is obtained.
Anticoagulants
Class Summary
Anticoagulants inhibit thrombogenesis.
Heparin
Heparin augments the activity of antithrombin III and prevents the conversion of
fibrinogen to fibrin. It does not actively lyse but is able to inhibit further
thrombogenesis. Heparin prevents the recurrence of a clot after spontaneous
fibrinolysis.
Low Molecular Weight Heparins
Class Summary
Low molecular weight heparins (LMWHs) inhibit thrombogenesis.
Enoxaparin (Lovenox)
Enoxaparin is produced by the partial chemical or enzymatic depolymerization of
unfractionated heparin (UFH). LMWH differs from UFH by having a higher ratio of
antifactor Xa to antifactor IIa.
Enoxaparin 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). It does not actively lyse but is able to inhibit further
thrombogenesis, preventing clot reaccumulation after spontaneous fibrinolysis.
The advantages of enoxaparin include intermittent dosing and a decreased
requirement for monitoring. Heparin antifactor Xa levels may be obtained if
needed to establish adequate dosing. There is no utility in checking activated
partial thromboplastin time (aPTT); the drug has a wide therapeutic window, and
aPTT does not correlate with the anticoagulant effect. The maximum antifactor
Xa and antithrombin activities occur 3-5 hours after administration.
Enoxaparin is indicated for the treatment of acute STEMI managed medically or
with subsequent percutaneous coronary intervention (PCI). It is also indicated as
prophylaxis for ischemic complications caused by unstable angina and non-Qwave myocardial infarction
Antiarrhythmic Agents
Class Summary
Antiarrhythmic agents reduce episodes of chest pain.
Esmolol (Brevibloc)

Esmolol is an ultrashort-acting agent that selectively blocks beta1 receptors

with little or no effect on beta2-receptor types. It is particularly useful in patients
with elevated arterial pressure, especially if surgery is planned. Esmolol has been
shown to reduce episodes of chest pain and clinical cardiac events compared
with placebo. It can be discontinued abruptly if necessary.
Esmolol is useful in patients at risk of experiencing complications from beta
blockade, particularly those with reactive airway disease, mild-moderate left
ventricular dysfunction, and/or peripheral vascular disease. The drug's short, 8minute half-life allows for titration to the desired effect and for quick
discontinuation if needed
Platelet Aggregation Inhibitors
Class Summary
These agents reduce platelet aggregation.
Abciximab (ReoPro)
Abciximab is a chimeric human-murine monoclonal antibody that has been
approved for use in elective/urgent/emergent PCI. It binds to the receptor with
high affinity and reduces platelet aggregation by 80% for up to 48 hours
following infusion
Loop Diuretics
Class Summary
Loop diuretics reduce blood pressure.
Furosemide (Lasix)
Furosemide increases the excretion of water by interfering with the chloridebinding cotransport system, which, in turn, inhibits sodium and chloride
reabsorption in the ascending loop of Henle and distal renal tubule. It increases
renal blood flow without increasing the filtration rate. The onset of action
generally is within 1 hour. Furosemide increases potassium, sodium, calcium, and
magnesium excretion.
The dose must be individualized to the patient. Depending on the response,
administer furosemide at increments of 20-40 mg, until the 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

Thiazide Diuretics
Class Summary
These agents reduce blood pressure.

Hydrochlorothiazide (Microzide)
Hydrochlorothiazide inhibits the reabsorption of sodium in distal tubules, causing
the increased excretion of sodium and water, as well as of potassium and
hydrogen ions
Antihypertensive Agents
Class Summary
Antihypertensive agents reduce blood pressure.
Spironolactone (Aldactone)
Spironolactone is used for the management of edema resulting from excessive
aldosterone excretion. It competes with aldosterone for receptor sites in the
distal renal tubules, increasing water excretion while retaining potassium and
hydrogen ions
Antiplatelet Agents
Class Summary
These agents inhibit platelet aggregation.
Eptifibatide (Integrilin)
Eptifibatide is an antagonist of the GP IIb/IIIa receptor; it reversibly prevents von
Willebrand factor, fibrinogen, and other adhesion ligands from binding to the GP
IIb/IIIa receptor. Eptifibatide inhibits platelet aggregation. Its effects persist over
the duration of maintenance infusion and are reversed when infusion ends.
Tirofiban (Aggrastat)
Tirofiban is a nonpeptide antagonist of the GP IIb/IIIa receptor. It is a reversible
antagonist of fibrinogen binding. When tirofiban is administered intravenously,
more than 90% of platelet aggregation is inhibited. The drug is approved for use
in combination with heparin for patients with unstable angina who are being
treated medically and for those undergoing PCI.
Clopidogrel (Plavix)
Clopidogrel selectively inhibits adenosine diphosphate (ADP) binding to the
platelet receptor and the subsequent ADP-mediated activation of the
glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. The drug
may have a positive influence on several hemorrhagic parameters and may exert
protection against atherosclerosis not only through the inhibition of platelet
function but also through changes in the hemorrhagic profile.
Clopidogrel has been shown to decrease cardiovascular death, myocardial
infarction, and stroke in patients with acute coronary syndrome (ie, unstable
angina, non-Q-wave myocardial infarction).

Angiotensin-converting Enzyme (ACE) Inhibitors

Class Summary

ACE inhibitors help to control blood pressure.

Lisinopril (Prinivil, Zestril)
Lisinopril prevents the conversion of angiotensin I to angiotensin II (a potent
vasoconstrictor), resulting in increased levels of plasma renin and a reduction in
aldosterone secretion.
Enalapril (Vasotec)
Enalapril also prevents the conversion of angiotensin I to angiotensin II, leading
to increased levels of plasma renin and reduced aldosterone secretion. The drug
helps to control blood pressure and proteinuria. Enalapril decreases the
pulmonary-to-systemic flow ratio in the catheterization laboratory and increases
the systemic blood flow in patients with relatively low pulmonary vascular
resistance.
The drug has a favorable clinical effect when it is administered over a long
period. It helps to prevent potassium loss in the distal tubules; the body
conserves potassium, and thus, less oral potassium supplementation is needed
Beta-adrenergic Blockers
Class Summary
These agents are used to reduce blood pressure.
Atenolol (Tenormin)
Atenolol is used to treat hypertension. It selectively blocks beta1 receptors, with
little or no affect on beta2 types. Beta-adrenergic blocking agents affect blood
pressure via multiple mechanisms; actions include a negative chronotropic effect
that decreases the heart rate at rest and after exercise, a negative inotropic
effect that decreases cardiac output, a reduction of sympathetic outflow from the
central nervous system (CNS), and a suppression of renin release from the
kidneys.
Atenolol is used to improve and preserve hemodynamic status by acting on
myocardial contractility, reducing congestion, and decreasing myocardial energy
expenditure.
Beta-adrenergic blockers reduce the inotropic state of the left ventricle, decrease
diastolic dysfunction, and increase left ventricular compliance, thereby reducing
the pressure gradient across the left ventricular outflow tract.
Atenolol reduces the heart rate, thus lowering myocardial oxygen consumption
and reducing the potential for myocardial ischemia. During intravenous
administration, carefully monitor the patient's blood pressure, heart rate, and
ECG.
Metoprolol (Lopressor, Toprol XL)
Metoprolol is a selective beta1-adrenergic receptor blocker that decreases the
automaticity of contractions. During intravenous administration, carefully
monitor the patient's blood pressure, heart rate, and ECG

Calcium Channel Blockers

Class Summary
Calcium channel blockers improve oxygen delivery to myocardial tissue.
Verapamil (Calan, Calan SR, Covera-HS, Verelan)
During depolarization, verapamil inhibits calcium ions from entering slow
channels and voltage-sensitive areas of vascular smooth muscle and
myocardium.
Diltiazem (Cardizem CD, Cardizem LA, Dilacor XR, Diltzac, Tiazac)
During depolarization, diltiazem inhibits the influx of extracellular calcium across
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.
Diltiazem decreases the conduction velocity in the atrioventricular (AV) node. It
also increases the refractory period, via the blockade of calcium influx. This, in
turn, stops reentrant phenomenon.
Diltiazem decreases myocardial oxygen demand by reducing peripheral vascular
resistance, reducing the heart rate by slowing conduction through the sinoatrial
(SA) and AV nodes, and reducing LV inotropy. The drug slows AV nodal conduction
time and prolongs AV nodal refractory period, which may convert
supraventricular tachycardia or slow the rate in atrial fibrillation. It 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. They may have beneficial longterm effects, but this remains uncertain.
Amlodipine (Norvasc)
Amlodipine is generally regarded as a dihydropyridine, although experimental
evidence suggests that it also may bind to the nondihydropyridine binding sites.
The drug is appropriate for the prophylaxis of variant angina.
Amlodipine has antianginal and antihypertensive effects. It blocks the
postexcitation release of calcium ions into cardiac and vascular smooth muscle,
thereby inhibiting the activation of adenosine triphosphatase (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.
Amlodipine also increases myocardial oxygen delivery in patients with
vasospastic angina. In addition, it may potentiate ACE inhibitor effects. During
depolarization, amlodipine inhibits calcium ions from entering slow channels and
voltage-sensitive areas of vascular smooth muscle and myocardium.

The drug benefits nonpregnant patients with systolic dysfunction, hypertension,

or arrhythmias and can be used during pregnancy if clinically indicated.
Amlodipine has a substantially longer half-life than nifedipine and diltiazem and
is administered daily

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