Takotsubo Cardiomyopathy

Updated: Jan 17, 2017
  • Author: Eric B Tomich, DO; Chief Editor: Erik D Schraga, MD  more...
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Overview

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 electrocardiography (ECG), and have elevated cardiac enzyme levels consistent with myocardial infarction (MI). (See the images below.) [1, 2] However, when the patient undergoes cardiac angiography, left ventricular (LV) apical ballooning is present, and there is no significant coronary artery stenosis. (See Presentation and Workup.) [3]

Electrocardiogram of a patient with takotsubo card Electrocardiogram of a patient with takotsubo cardiomyopathy demonstrating ST-segment elevation in anterior and inferior leads.
Electrocardiogram from the same patient examined i 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 of TCM 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. The diagnosis requires the presence of all four of the following (see Workup):

  • Transient hypokinesis, dyskinesis, or akinesis of the LV 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 ECG abnormalities (either ST-segment elevation and/or T-wave inversion) or modest elevation in the cardiac troponin level
  • Absence of pheochromocytoma or myocarditis [5]
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Pathophysiology

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 glucose is largely utilized instead, which results 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 LV segments. [6]

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 LV wall-motion abnormality of TCM. Whether this is triggered by multivessel spasm, thrombosis, epicardial vessel occlusion, or direct myocardial toxicity remains to be seen. These authors point out that the wall-motion abnormality of TCM can be seen in other conditions, including those with certain left anterior descending (LAD) lesions, [7]  making wall motion alone insufficient for the diagnosis of TCM. [8]

Cases of TCM have been reported in the literature following cocaine, methamphetamine, and excessive phenylephrine use. [9, 6]  Exercise stress testing, which is known to cause increased levels of catecholamines, has resulted in false positives attributable to TCM. [10]  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 MI. [11]  The apical portions of the LV have the highest concentration of sympathetic innervation found in the heart and may explain why excess catecholamines seem to selectively affect its function. [6]

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Etiology

The exact etiology of TCM is still unknown, but several theories have been proposed and are being investigated. [12] These include the following [9, 13] :

  • Multivessel coronary artery spasm
  • Impaired cardiac microvascular function
  • Impaired myocardial fatty acid metabolism
  • ACS with reperfusion injury
  • Endogenous catecholamine-induced myocardial stunning and microinfarction

Risk factors

A significant emotional or physical stressor or neurologic injury typically precedes the development of the TCM. [4] Stressors include the following:

  • 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 (ICU) stay
  • 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 was more likely to exacerbate TCM than mental stress was. [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 by means of echocardiography in conjunction with ventriculography. [16]

Similarly, the International Takotsubo Registry reported that patients with TCM, as compared with ACS patients, were more likely to be female (89.8%) and that physical triggers were more common than emotional triggers (36% vs 27.7%), though more than one quarter (28.5%) had no clear triggers. [17] Patients with TCM also had higher rates of neurologic or psychiatric disorders and a significantly lower LV ejection fraction (LVEF). The two groups (TCM and ACS) had similar rates of severe inpatient complications (eg, shock, death), and independent predictors of such complications included physical triggers, acute neurologic/psychiatric diseases, elevated troponin levels, and low LVEF. [17]

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Epidemiology

Studies reported that 1.7-2.2% of patients who had suspected ACS were subsequently diagnosed with TCM. [18, 19] Patients are typically Asian or Caucasian. In a literature review of cases in which race was reported, 57.2% of patients were Asian, 40% were Caucasian, and 2.8% were other races. [20]

Literature reviews report a mean patient age of 67 years, though cases of TCM have occurred in children and young adults [9, 11] Nearly 90% of reported cases involve postmenopausal women. [21]

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Prognosis

The prognosis in 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 have ranged from 1% to 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
  • LV outflow obstruction
  • Mitral regurgitation
  • Ventricular arrhythmias
  • LV mural thrombus formation
  • LV free-wall rupture
  • Death [25, 26]
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