Pheochromocytoma triggers takotsubo syndrome

This commentary refers to ‘Takotsubo syndrome’s pathophysiology: still a mystery?’, by F. Pelliccia et al., on page 1989. We highly appreciate the comments by Pelliccia et al.1 on our Consensus articles on takotsubo syndrome (TTS) published recently in the European Heart Journal. 2 , 3 The consensus statement is based on a broad agreement of experts in TTS dealing with issues where uncertainties exist to provide support in daily clinical practice and to give up to date scientific knowledge in the field of TTS. Indeed, TTS is a syndrome and as such is precipitated by different triggers of physical or emotional nature as well as of unknown stimuli. In line with the current literature and up-to-date knowledge and in contrast to Pelliccia et al. pheochromocytoma as any other physical stressor may trigger TTS. Pheochromocytoma triggered TTS may act through activation of sympathetic nervous system including hyperactivation and disruption of the local cardiac sympathetic nerve terminals and norepinephrine spillover. Furthermore, pheochromocytoma-triggered TTS has clinical characteristics, cardiac imaging findings, and histopathological features, which do not differ from other emotional- or physical-triggered TTS.4 However, pheochromocytoma is a robust, and durable trigger partly due to the severe symptoms related to pheochromocytoma (dizziness, palpitation, and hypertension) and partly due to catecholamine storm. This may result in a severe type of TTS which is reflected in high in-hospital complication rates (67.9%) and cardiogenic shock (34.6%).4 We certainly acknowledge the excellent work by Ferreira et al.5 The authors of that study, however, investigated patients with pheochromocytoma in general and not specifically those that present as a TTS. There is no information about the clinical picture including symptoms, ECG, and biomarkers. It goes without saying that not every patient who has pheochromocytoma develops the phenotype of TTS. Indeed, phenocopy is just another word for syndrome that also assembles phenotypes of different origin in medicine at large. In opposite to Pellicia et al.,1 we would like to clarify that inflammatory changes6 have been observed in TTS and fibrosis has also been detected to replace myocardial oedema. 7 Although, as mentioned by Pelliccia et al., catecholamines surges have been described in acute TTS patients, not all investigated TTS patients have shown elevated catecholamine levels. If catecholamines would be the only mediator of TTS, then every patient with a ‘catecholamine storm’ would have to develop TTS. But this is obviously not the case. Overall therefore, our experts felt that there is currently no convincing reason to exclude pheochromocytoma as a potential triggering factor for TTS development. Conflict of interest: none declared.