Long-Term Prognosis in Patients with Takotsubo Syndrome

This article refers to ‘Long-term outcome in patients with Takotsubo syndrome presenting with severely reduced left ventricular ejection fraction’ by R. Citro et al., published in this issue on pages 781–789. In this issue of the Journal, Citro and colleagues sought to assess the long-term prognosis of Takotsubo syndrome (TTS) patients with reduced left ventricular ejection fraction (LVEF).1 LVEF < 35% on admission was a prognostic indicator not only in the acute phase but also in the long-term follow-up period in TTS patients. Although various studies have already presented enough clinical data in TTS, this study provides directly associated hints and tips in TTS prognosis. Takotsubo syndrome was previously thought to be a benign condition, not requiring any specific treatments; however, nowadays the prognosis of TTS is regarded not as optimistic as before due to several complications and life-threatening conditions. El-Battrawy et al.2 demonstrated that LVEF < 35% was an independent predictor of short- and long-term mortality in TTS patients. Citro et al.1 reported the results of 326 patients with TTS from the Italian multicenter registry data that included approximately three times as much as the previous published data. Recently, the RETAKO registry promoted by a Spanish researcher group reported that cardiogenic shock was associated with short- and long-term prognosis in patients with TTS.3 Decreased systolic blood pressure on admission is thought to be a prognostic indicator in TTS patients4; thus, these findings support risk stratification, which has previously been proposed and described in a European Society of Cardiology (ESC) position statement.5 In this study, many TTS patients with LVEF < 35% were elderly; old age was the independent prognostic predictor even in multivariate analysis. The authors reported that reduced beta1-adrenergic receptor density was the cause of this phenomenon. However, attention should be paid to the increased incidence of mitral regurgitation (MR) in the aged TTS patients. MR in TTS patients is frequently triggered by systolic anterior motion of the mitral anterior leaflet and the tethering by papillary muscle displacement along with regional or global ventricular dysfunction.6 In this study, no significant differences were found in left ventricular outflow tract obstruction (LVOTO) in TTS patients regardless of left ventricular systolic function. We need to precisely evaluate the presence of LVOTO in the elderly, that is because we encounter patients with sigmoid septum and concentric hypertrophy of the left ventricle. Not only functional alternation but also left ventricular anatomical change in the elderly might affect the unfavourable outcome in TTS in the acute phase. The most common clinical complication in TTS patients is heart failure with or without pulmonary oedema. The authors have previously clarified that E/e' ratio is an independent predictor of heart failure and in-hospital mortality in multivariate analyses.7 Citro et al.1 also demonstrated that TTS patients with LVEF < 35% taking beta-blockers showed a lower incidence of major adverse cardiac events compared to those not taking beta-blockers. Several studies, though not prospective or randomized, demonstrated that beta-blocker administration did not contribute to better outcome8 or recurrence prevention9 In this study, a similar trend can be seen in TTS patients with LVEF > 35%. Given that the ESC position statement5 and an international expert consensus10 have advised beta-blocker intake in TTS patients with low risks, the results of this study support this recommended treatment regardless of LVEF. When we treat TTS patients with LVOTO, beta-blocker administration should first be considered. Intra-aortic balloon pumping is contraindicated in TTS patients with LVOTO in order not to reduce their afterload. The administration of beta-blockers should be also cautious in TTS patients presenting with bradycardia. Takotsubo syndrome is known to be characterized by a wide variety of wall motion abnormalities. Approximately 80% of TTS patients have a typical and classical apical ballooning type.11 The remaining 20% of patients show a mid-ventricular, basal and focal pattern.11 In the BOREAS-TCM registry, data accumulated in Japan demonstrated no significant differences in prognosis between TTS patients with and without apical ballooning.12 Ghadri et al.13 evaluated prognosis in TTS patients according to their wall motion abnormalities. Patients with the atypical type had better prognosis than those with the typical type in the first year after TTS onset; however, mortality rates were comparable afterwards. Current InterTAK registry data have clarified the long-term prognosis in TTS patients.14 TTS patients had a comparable long-term mortality risk with those with acute coronary syndrome. Additionally, patients with classical TTS due to emotional stress had a favourable short- and long-term prognosis. These results were the same as what I presumed. Considering from the standpoint of prognosis, personalized treatment strategy and follow-up are mandatory in TTS. In the All New Zealand Acute Coronary Syndrome Quality Improvement Program,15 in-hospital mortality of TTS patients was equivalent to that of patients with acute coronary syndrome, whereas TTS patients had better long-term survival than acute coronary syndrome patients after discharge. Even in the southern hemisphere, the trend in prognosis was quite similar to that in the northern hemisphere.15 Accordingly, long-term prognosis in TTS patients becomes favourable when adequate and accurate treatment is provided in the acute phase. It is necessary to reconsider the prognosis of TTS patients. Conflict of interest: none declared.