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.

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.

Cardiovascular diseases (CVD) and mental health disorders (MHD) are respectively the first and second most prevalent diseases in high-income countries and the two most relevant causes of disability worldwide. The close association between the two conditions has been known for a long time and research has been able to document how the co-morbidity between cardiovascular disorders and mental health disorders is a negative prognostic factor for both conditions. This strong connection and the relevance of the impact of the association have led to define a new branch of cardiology, known as behavioral cardiology. The aim of the new branch is just to study the nexus CVD-MHD in order to prevent or decrease the burden of MHD on CVD and vice versa. This review describes the epidemiological evidence of the relationship between MHD on CVD at the state of the art among clinical research.

Introduction: Depression is a common and severe comorbidity among individuals with heart failure (HF). Up to a third of all HF patients are depressed, and an even higher proportion have symptoms of depression. Aim: In this review, we evaluate the relationship between HF and depression, explain the pathophysiology and epidemiology of both diseases and their relationship, and highlight novel diagnostic and therapeutic options for HF patients with depression. Materials and Methods: This narrative review involved keyword searches of PubMed and Web of Science. Review search terms included [“Depression” OR “Depres*” OR “major depr*”] AND [“Heart Failure” OR “HF” OR “HFrEF” OR “HFmrEF” OR “HFpEF” OR “HFimpEF”] in all fields. Studies included in the review met the following criteria: (A) published in a peer-reviewed journal; (B) described the impact of depression on HF and vice versa; and (C) were opinion papers, guidelines, case studies, descriptive studies, randomized control trials, prospective studies, retrospective studies, narrative reviews, and systematic reviews. Results: Depression is an emergent HF risk factor and strongly relates with worse clinical outcomes. HF and depression share multiple pathways, including platelet dis-reactivity, neuroendocrine malfunction, inappropriate inflammation, tachi-arrhythmias, and frailty in the social and community setting. Existing HF guidelines urge evaluation of depression in all HF patients, and numerous screening tools are available. Depression is ultimately diagnosed based on DSM-5 criteria. There are both non-pharmaceutical and pharmaceutical treatments for depression. Regarding depressed symptoms, non-pharmaceutical treatments, such as cognitive-behavioral therapy and physical exercise, have shown therapeutic results, under medical supervision and with an effort level adapted to the patient’s physical resources, together with optimal HF treatment. In randomized clinical studies, selective serotonin reuptake inhibitors, the backbone of antidepressant treatment, did not demonstrate advantage over the placebo in patients with HF. New antidepressant medications are currently being studied and could provide a chance to enhance management, treatment, and control of depression in patients with HF. Conclusions: Despite the substantial link between depression and HF, their combination is underdiagnosed and undertreated. Considering the hopeful yet unclear findings of antidepressant trials, further research is required to identify people who may benefit from antidepressant medication. The goal of future research should be a complete approach to the care of these patients, who are anticipated to become a significant medical burden in the future.

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.