Takotsubo Cardiomyopathy 

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] 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.)^[2]

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

The modified Mayo Clinic criteria for diagnosis of TCM 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^[3]

The exact etiology of takotsubo cardiomyopathy (TCM) is still unknown, but several theories have been proposed and are being investigated.^[4] 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.^{[5, 6]}

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.^[7]

The most commonly discussed possible mechanism for TCM is stress-induced catecholamine release, with toxicity to and subsequent stunning of the myocardium. 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,^[8] making wall motion alone insufficient for the diagnosis of TCM.^[9]

Cases of TCM have been reported in the literature following cocaine, methamphetamine, and excessive phenylephrine use.^{[5, 7]} 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 myocardial infarctions.^[11] 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.^[7]

Risk factors

A significant emotional or physical stressor typically precedes the development of the 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; 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.^[12]

Studies reported that 1.7-2.2% of patients who had suspected acute coronary syndrome were subsequently diagnosed with takotsubo cardiomyopathy (TCM).^{[13, 14]} 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.^[15]

Literature reviews report a mean patient age of 67 years, although cases of TCM have occurred in children and young adults^{[5, 11]} Nearly 90% of reported cases involve postmenopausal women.^[16]

The prognosis in takotsubo cardiomyopathy (TCM) is excellent, with nearly 95% of patients experiencing complete recovery within 4-8 weeks. The recurrence rate varies but is estimated at 3%.^{[17, 18]} Estimates of mortality rates have ranged from 1-3.2%.^{[16, 15]}

Complications occur in 20% of TCM 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^{[19, 20]}