OBJECTIVE In view of low prevalence rates, diabetes is discussed as a protective factor for the occurrence of Takotsubo syndrome (TTS). Furthermore, it was associated with improved outcome in a small single-center analysis. Therefore, this study assessed the prevalence and prognostic relevance of concomitant diabetes in TTS. RESEARCH DESIGN AND METHODS A total of 826 patients with TTS were enrolled in an international, multicenter, registry-based study (eight centers in Italy and Germany). All-cause mortality was compared between patients with diabetes and patients without diabetes, and the independent predictive value of diabetes was evaluated in multivariate regression analysis. RESULTS The prevalence of diabetes was 21.1% (n = 174). TTS patients with diabetes were older (P < 0.001), were more frequently male (P = 0.003), had a higher prevalence of hypertension (P < 0.001), physical triggers (P = 0.041), and typical apical ballooning (P = 0.010), had a lower left ventricular ejection fraction (P = 0.008), had a higher rate of pulmonary edema (P = 0.032), and had a longer hospital stay (P = 0.009). However, 28-day all-cause mortality did not differ between patients with diabetes and patients without diabetes (6.4% vs. 5.7%; hazard ratio [HR] 1.11 [95% CI 0.55–2.25]; P = 0.772). Longer-term follow-up after a median of 2.5 years revealed a significantly higher mortality among TTS patients with diabetes (31.4% vs. 16.5%; P < 0.001), and multivariate regression analysis identified diabetes as an independent predictor of adverse outcome (HR 1.66 [95% CI 1.16–2.39]; P = 0.006). CONCLUSIONS Diabetes is not uncommon in patients with TTS, is associated with increased longer-term mortality rates, and is an independent predictor of adverse outcome irrespective of additional risk factors.

First recognized in 1990, takotsubo syndrome (TTS) constitutes an acute cardiac condition that mimics acute myocardial infarction commonly in the absence of obstructive coronary artery disease; it is characterized by temporary left ventricular dysfunction, regularly in a circumferential apical, midventricular, or basal distribution. Considering its acute clinical presentation, coronary angiography with left ventriculography constitutes the gold standard diagnostic tool to exclude or confirm TTS. Frequently, TTS is related to severe emotional or physical stress and a subsequent increased adrenergic stimulation affecting cardiac function. Beyond clinical presentation, epidemiology, and novel diagnostic biomarkers, this review draws attention to potential pathophysiological mechanisms for the observed reversible myocardial dysfunction such as sympathetic overdrive-mediated multi-vessel epicardial spasms, microvascular dysfunction, the direct toxicity of catecholamines, lipotoxicity, and inflammation. Considering the long-term prognosis, further experimental and clinical research is indispensable to elucidate further pathophysiological mechanisms underlying TTS before randomized control trials with evidence-based therapeutic management can be performed.

Takotsubo syndrome (TTS) is a unique nonischemic cardiac disease characterized by acute myocardial dysfunction of the left and/or right ventricle. Patients are predominantly postmenopausal women and usually present with symptoms indistinguishable from acute coronary syndrome. Although the exact pathomechanisms of TTS remain elusive, increasing evidence suggests that sympathetic overdrive and catecholamine excess might play a central role. Despite the complete recovery of ventricular dysfunction within several days to weeks, patients with TTS exhibit considerable short‐ and long‐term mortality rates and ventricular arrhythmias have been identified as key contributor to morbidity and mortality. This article summarizes the prevalence, underlying mechanisms, therapeutic strategies, and prognostic implications of ventricular arrhythmias in TTS. Furthermore, the need for implantable cardioverter‐defibrillators is discussed in view of the transient character of the disease.

Background: Takotsubo syndrome is usually triggered by a stressful event. The type of trigger seems to influence the outcome and should therefore be considered separately. Methods and Results: Patients included in the GEIST (German‐Italian‐Spanish Takotsubo) registry were categorized according to physical trigger (PT), emotional trigger (ET), and no trigger (NT) of Takotsubo syndrome. Clinical characteristics as well as outcome predictors were analyzed. Overall, 2482 patients were included. ET was detected in 910 patients (36.7%), PT in 885 patients (34.4%), and NT was observed in 717 patients (28.9%). Compared with patients with PT or NT, patients with ET were younger, less frequently men, and had a lower prevalence of comorbidities. Adverse in‐hospital events (NT: 18.8% versus PT: 27.1% versus ET: 12.1%, P <0.001) and long‐term mortality rates (NT: 14.4% versus PT: 21.6% versus ET: 8.5%, P <0.001) were significantly lower in patients with ET. Increasing age ( P <0.001), male sex ( P =0.007), diabetes ( P <0.001), malignancy ( P =0.002), and a neurological disorder ( P <0.001) were associated with a higher risk of long‐term mortality, while chest pain ( P =0.035) and treatment with angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker ( P =0.027) were confirmed as independent predictors for a lower risk of long‐term mortality. Conclusions: Patients with ET have better clinical conditions and a lower mortality rate. Increasing age, male sex, malignancy, a neurological disorder, chest pain, angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker, and diabetes were confirmed as predictors of long‐term mortality.

Takotsubo syndrome (TTS) represents a form of acute heart failure featured by reversible left ventricular systolic dysfunction. The management during the acute phase is mainly performed with supportive pharmacological (diuretics, ACE-inhibitors/angiotensin-receptor blockers (ARBs), anticoagulants, antiarrhythmics, non-catecholamine inotropics (levosimendan), and non-pharmacological (mechanical circulatory and respiratory support) therapy, due to the wide clinical presentation and course of the disease. However, there is a gap in evidence and there are no randomized and adequately powered studies on clinical effectiveness of therapeutic approaches. Some evidence supports the use ACE-inhibitors/ARBs at long-term. A tailored approach based on cardiovascular and non-cardiovascular risk factors is strongly suggested for long-term management. The urgent need for evidence-based treatment approaches is also reflected by the prognosis following TTS. The acute phase of the disease can be accompanied by various cardiovascular complications. In addition, long term outcome of TTS patients is also related to non-cardiovascular comorbidities. Physical triggers such as hypoxia and acute neurological disorders in TTS are associated with a poor outcome.