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.

Background: Neurological disorders as a risk factor for Takotsubo syndrome (TTS) are not well characterized. The aim of the study was to evaluate TTS‐associated neurological phenotypes and outcome. Methods and Results: Patients with TTS enrolled in the international multicenter GEIST (German Italian Spanish Takotsubo) registry were analyzed. Prevalence, clinical characteristics, and short‐ and long‐term outcomes of patients with TTS were recorded. A subgroup analysis of the 5 most represented neurological disorders was performed. In total, 400 (17%) of 2301 patients had neurological disorders. The most represented neurological conditions were previous cerebrovascular events (39%), followed by neurodegenerative disorders (30.7%), migraine (10%), epilepsy (9.5%), and brain tumors (5%). During hospitalization, patients with neurological disorders had longer in‐hospital stay (8 [interquartile range, 5–12] versus 6 [interquartile range, 5–9] days; P <0.01) and more often experienced in‐hospital complications (27% versus 16%; P =0.01) mainly driven by cardiogenic shock and in‐hospital death (12% versus 7.6% and 6.5% versus 2.8%, respectively; both P <0.01). Survival analysis showed a higher mortality rate in neurological patients both at 60 days and long‐term (8.8% versus 3.4% and 23.5% versus 10.1%, respectively; both P <0.01). Neurological disorder was an independent predictor of both the 60‐day and long‐term mortality rate (odds ratio, 1.78 [95% CI, 1.07–2.97]; P =0.02; hazard ratio, 1.72 [95% CI, 1.33–2.22]; both P <0.001). Patients with neurodegenerative disorders had the worst prognosis among the neurological disease subgroups, whereas patients with TTS with migraine had a favorable prognosis (long‐term mortality rates, 29.2% and 9.7%, respectively). Conclusions: Neurological disorders identify a high‐risk TTS subgroup for enhanced short‐ and long‐term mortality rate. Careful recognition of neurological disorders and phenotype is therefore needed.

Background: The role of age in the short‐ and long‐term prognosis of takotsubo syndrome (TTS) is controversial. The aim of the present study was to evaluate age‐related differences and prognostic implications among patients with TTS. Methods and Results: In total, 2492 consecutive patients with TTS enrolled in an international registry were stratified into 4 groups (<45, 45–64, 65–74, and ≥75 years). The median long‐term follow‐up was 480 days (interquartile range, 83–1510 days). The primary outcome was all‐cause mortality (in‐hospital and out‐of‐hospital mortality). The secondary end point was TTS‐related in‐hospital complications. Among the 2479 patients, 58 (2.3%) were aged <45 years, 625 (25.1%) were aged 45 to 64 years, 733 (29.4%) were aged 65 to 74 years, and 1063 (42.6%) were aged ≥75 years. Young patients (<45 years) had a higher prevalence of men (from youngest to oldest, 24.1% versus 12.6% versus 9.7% versus 11.4%; P <0.01), physical triggers (46.6% versus 27.5%, 33.9%, and 38.4%; P <0.01), and non‐apical forms of TTS (25.9% versus 23.7%, 12.7%, and 9%; P <0.01) than those aged 45 to 64, 65 to 74, and ≥75 years. During hospitalization, young patients experienced a higher rate of in‐hospital complications (32.8% versus 23.4%, 27.4%, and 31.9%; P =0.01), but in‐hospital mortality was higher in the older group (0%, 1.6%, 2.9%, and 5%; P =0.001). Long‐term all‐cause mortality was significantly higher in the older cohort (5.6%, 6.4%, 11.3%, and 22.3%; log‐rank P <0.001), as was long‐term cardiovascular mortality (0%, 0.9%, 1.9%, and 3.2%; log‐rank P =0.01). Conclusions: Young patients with TTS have a typical phenotype characterized by a higher prevalence of male sex, non‐apical ballooning patterns, and in‐hospital complications. However, in‐hospital and long‐term mortality are significantly lower in young patients with TTS. Registration: URL: https://classic.clinicaltrials.gov/ct2/show/NCT04361994 . Unique identifier: NCT04361994.

Atherosclerotic coronary artery disease remains a leading cause of morbidity and mortality worldwide, despite advances in lipid-lowering and antithrombotic therapies. Increasing evidence highlights the pivotal role of inflammation in all stages of atherosclerosis, from plaque formation to rupture. Colchicine, a well-known anti-inflammatory drug traditionally used in gout and pericarditis, has emerged as a promising agent in the secondary prevention of cardiovascular events. Recent clinical trials have demonstrated significant reductions in cardiovascular outcomes with low-dose colchicine, especially in patients with stable CAD and following myocardial infarction. This review provides an updated overview of the pathophysiological rationale for colchicine use in atherosclerosis, summarizes key clinical trial data, and discusses potential mechanisms, safety considerations, and future directions.