A 64-Year-Old Woman With Extremity Swelling and Cough

Francisco Aguilar, MD; Carla Arellano Pizano, MD


July 17, 2018

The pathophysiology of Takotsubo cardiomyopathy is unclear. The reason that it more commonly affects postmenopausal women and the left ventricle apex and midsegments is not certain. Several studies have found elevated levels of catecholamines in patients with Takotsubo cardiomyopathy. The relationship with a stressor suggests that this event promotes the release of catecholamines, which cause myocardial stunning that is mediated by coronary artery spasms or direct myocardial toxicity. This theory is supported by an animal study model in which rats that were exposed to physical stressors were found to have elevated catecholamine levels and left ventricular apical ballooning.[3,4] The same authors found that these changes were prevented by alpha-blockade or beta-blockade.

Other studies propose microvascular abnormalities and hormonal environment as the main pathophysiologic mechanism that predispose to a transient obliteration of the coronary arteries in the presence of a stressor. The predominance of postmenopausal women has suggested that these changes may be related to decreased estrogenic influence.[2,3,4] The clinical presentation often mimics acute coronary syndrome. The most common presenting symptoms include chest pain and shortness of breath; ventricular arrhythmias and cardiogenic shock are less frequently reported.

Ischemic ECG changes commonly include ST elevation/depression and T-wave inversion. Mild troponin leak is also a common finding, which makes this syndrome more challenging to differentiate from acute coronary syndromes.[5] BNP and N-terminal pro-BNP levels are elevated in as many as 82% of cases, with a median value of six times the upper limit of normal values.[6]

The most common complication is heart failure, with or without pulmonary edema; however, these patients can also develop cardiogenic shock and left ventricular thrombus. Diagnosis is often challenging because the initial presentation often misleadingly suggests acute coronary syndrome. The modified Mayo Clinic criteria for diagnosis require four elements to be present, including:[7]

  • Transient hypokinesis, dyskinesis, or akinesis of the left ventricle midsegments, with or without apical involvement; the regional wall-motion abnormalities extend beyond a single epicardial vascular distribution

  • 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 cerebrovascular disease, pheochromocytoma, or myocarditis

Transthoracic echocardiography is an accessible, quick, and reliable diagnostic tool that can reveal the typical wall motion abnormalities described above. Echocardiography is also helpful in detecting the presence of a left ventricular thrombus. As many as 5% of cases have evidence of a left ventricular thrombus.[2] Embolization from this left ventricular thrombus is a potential complication. Coronary angiography is required for diagnosis and helps differentiate this entity from acute coronary syndrome. Most patients with Takotsubo cardiomyopathy have normal coronary arteries or nonsignificant coronary artery disease.[2] Left ventriculography performed during left heart catheterization reveals the characteristic pattern of apical ballooning during systole, providing the best imaging for diagnosis.

The primary differential diagnosis of this condition is acute coronary syndrome. Although both conditions can coexist, Takotsubo cardiomyopathy involves a myocardial territory that cannot be explained by the affected coronary artery. Other conditions that can present similarly include cocaine-induced acute coronary syndrome, myocarditis, pheochromocytoma, and acute brain injury.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.