We commend Citro et al . on their comprehensive review article regarding the clinical and prognostic implications of echocardiographic techniques in takotsubo cardiomyopathy. In particular, we found the section on myocardial contrast echocardiography to be of great value. However, we would like to draw attention to Table 4 of the article, which outlines the disadvantages of contrast echocardiography: “Several contrast agents are not indicated in acute ill patients.” We would like to propose that this statement is not supported by the current evidence base, nor is it based on official product information statements for contrast agents.

There are three echocardiographic contrast agents commercially available and in clinical use: Definity (Lantheus Medical Imaging, North Billerica, MA), Optison (GE Healthcare, Little Chalfont, United Kingdom), and SonoVue (Bracco Diagnostics, Milan, Italy). Contrast-enhanced transthoracic echocardiography is a well-accepted imaging modality used to enhance endocardial border detection when baseline images are suboptimal or nondiagnostic. Despite being used by many echocardiographic laboratories, contrast perfusion imaging (including in stress cardiomyopathy) would be considered an “off-label” use of contrast agents. Although it is recognized that these agents are safe and well tolerated, like all contrast agents used in medicine, they do have recognized side effects and specific contraindications. Definity and Optison are contraindicated in patients with hypersensitivity to perflutren and right-to-left, bidirectional, or transient right-to-left cardiac shunts. Optison contains a 1% human albumin shell, so hypersensitivity to blood or blood products is included as an additional contraindication. A third contrast agent, SonoVue, has similar contraindications as Definity and Optison but is also contraindicated in patients with severe pulmonary hypertension (pulmonary artery pressure > 90 mm Hg), uncontrolled systemic hypertension, adult respiratory distress syndrome, and “in combination with dobutamine in patients with conditions suggesting cardiovascular instability where dobutamine is contraindicated.” The administration of these contrast agents should be considered on the basis of the potential risk, the potential benefit, and what alternatives are available in the quest for a diagnostic study.

The safety of these agents has been extensively investigated, and importantly, they have been shown to be safe in a broad range of medical conditions, including acutely unwell patients. The current contraindications for intracardiac shunts and severe pulmonary hypertension are also in debate, with growing evidence for the safety of contrast in these settings. There are therefore few absolute contraindications to contrast administration, especially in those who are acutely unwell.

We feel that more suitable disadvantages that could be listed include difficulties with standardization of technique (especially myocardial contrast echocardiography), availability of contrast agents and contrast imaging at different centers, and staff experience and education in the use of these agents. The safety of microsphere contrast echocardiography is well established, including in acutely ill patients. These patients often have suboptimal image quality but may obtain the most benefit from accurate, timely, and bedside evaluation of cardiac function. Consequently, it is particularly in this population that contrast echocardiography may be of the greatest utility. As such, we should be cognizant that these patients are not excluded from the potential benefits of this generally safe, accurate, portable cardiac imaging modality.