We are very grateful to Drs Putrino and Platts for their comprehensive letter pointing out the safety of contrast echocardiography (CE) in acutely ill patients. We are in full agreement about the value of CE and the safety and tolerability of all the echocardiographic contrast agents available on the market: Definity (Lantheus Medical Imaging, North Billerica, MA), Optison (GE Healthcare, Little Chalfont, United Kingdom) and SonoVue/Lumason (Bracco Imaging, Milan, Italy/Bracco Diagnostics, Monroe Township, NJ). We also agree on the need for global standardization of contrast imaging techniques and the importance of staff experience. Adequate education in the use of these agents is a conditio sine qua non to obtain the most benefit from this imaging modality.

We recognize that the statement “several contrast agents are not indicated in acute ill patients” in Table 4 of our review of the clinical and prognostic implications of echocardiography in takotsubo syndrome (TTS) was misleading. However, it should be specified that we were referring to the cultural bias related to the restriction imposed by the European Agency for the Evaluation of Medicinal Products on use of SonoVue, the most commonly used contrast agent in Europe, in patients with recent (< 7 days) acute coronary syndromes. This warning was introduced in 2004 and has been revised only recently (May 2014). Currently, contrast agents are not contraindicated in acutely ill patients and can be administered after careful risk assessment and with close monitoring for 30 min of vital signs, electrocardiogram, and cutaneous oxygen saturation. Although no absolute contraindication exists to the use of contrast media, this caution should be strongly observed given the risk for hemodynamic instability, especially in the early phase of TTS.

Besides the safety and tolerability of contrast agents, we would like to point out the advantages of CE in the specific setting of patients with TTS. First of all, in patients with poor acoustic windows, CE enables accurate left ventricular (LV) endocardial border definition and the identification of different morphologic patterns of TTS (apical ballooning, midventricular, or inverted). Furthermore, because of the well-known intrinsic limitation of echocardiography in assessing the right ventricle, a lower infusion rate of contrast medium might be helpful to recognize the “biventricular ballooning” pattern. Ventricular opacification may be useful not only to assess LV volumes and ejection fraction phase but also to monitor myocardial contractility recovery during follow-up. Of note, reduced ejection fraction on hospital admission correlates with worse in-hospital outcomes and is associated with delayed recovery, especially in elderly patients. Although the use of CE has been approved for only one major indication (i.e., LV opacification when the endocardial border is not adequately visualized on baseline images), some off-label applications could be helpful in clinical practice, particularly in TTS. In this respect, patients with apical ballooning and persistent myocardial dysfunction are at higher risk for developing intraventricular thrombi, which could be visualized more clearly as a filling defect of the LV apex by using contrast agents. This could represent a relevant application of CE in TTS as a guide to start anticoagulant therapy to minimize the risk for systemic embolization. Another potential clinical application of CE includes the assessment of myocardial perfusion. Several clinical and experimental studies investigated coronary microcirculation integrity in the early phase of TTS. However, there are conflicting results, and the role of microcirculation in TTS remains to be clarified. We hope that current availability of contrast agents in the intensive care unit will provide a new impulse to additional studies on the use of CE, so as to better define its clinical applications in the evaluation of LV morphology and function, thromboembolic risk, and myocardial perfusion.