Shaping the Neurovascular Unit Exploiting Human Brain Organoids.

Brain organoids, three-dimensional cell structures derived from pluripotent stem cells, closely mimic key aspects of the human brain in vitro, providing a powerful tool for studying neurodevelopment and disease. The neuroectodermal induction protocol employed for brain organoid generation primarily gives rise to the neural cellular component but lacks the vital vascular system, which is crucial for the brain functions by regulating differentiation, migration, and circuit formation, as well as delivering oxygen and nutrients. Many neurological diseases are caused by dysfunctions of cerebral microcirculation, making vascularization of human brain organoids an important tool for pathogenetic and translational research. Experimentally, the creation of vascularized brain organoids has primarily focused on the fusion of vascular and brain organoids, on organoid transplantation in vivo, and on the use of microfluidic devices to replicate the intricate microenvironment of the human brain in vitro. This review summarizes these efforts and highlights the importance of studying the neurovascular unit in a forward-looking perspective of leveraging their use for understanding and treating neurological disorders.

Genomic and transcriptomic advances in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder and the most common motor neuron disease. ALS shows substantial clinical and molecular heterogeneity. In vitro and in vivo models coupled with multiomic techniques have provided important contributions to unraveling the pathomechanisms underlying ALS. To date, despite promising results and accumulating knowledge, an effective treatment is still lacking. Here, we provide an overview of the literature on the use of genomics, epigenomics, transcriptomics and microRNAs to deeply investigate the molecular mechanisms developing and sustaining ALS. We report the most relevant genes implicated in ALS pathogenesis, discussing the use of different high-throughput sequencing techniques and the role of epigenomic modifications. Furthermore, we present transcriptomic studies discussing the most recent advances, from microarrays to bulk and single-cell RNA sequencing. Finally, we discuss the use of microRNAs as potential biomarkers and promising tools for molecular intervention. The integration of data from multiple omic approaches may provide new insights into pathogenic pathways in ALS by shedding light on diagnostic and prognostic biomarkers, helping to stratify patients into clinically relevant subgroups, revealing novel therapeutic targets and supporting the development of new effective therapies.

A Multiaxial Rehabilitation Programme for Workers with COVID-19 Sequelae Using a Conventional and Technological-Robotic Approach: The Proposal of INAIL and Fondazione Don Carlo Gnocchi.

The COVID-19 sequelae have been shown to affect respiratory and cardiological functions as well as neuro-psychological functions, and, in some cases, metabolic/nutritional aspects. The Italian National Institute for Insurance against Accidents at Work (Istituto Nazionale Assicurazione Infortuni sul Lavoro, INAIL) recorded that, until December 2022, 315,055 workers were affected by COVID-19; therefore, there is a need to identify an effective approach to treat such patients. Robotic and technological devices could be integrated into the rehabilitation programme of people with long COVID conditions. A review of the literature showed that telerehabilitation may improve functional capacity, dyspnoea, performance, and quality of life in these patients, but no studies were found evaluating the effects of robot-mediated therapy or virtual reality systems. Considering the above, Fondazione Don Carlo Gnocchi and INAIL propose a multi-axial rehabilitation for workers with COVID-19 sequelae. To accomplish this goal, the two institutions merged the epidemiological information gathered by INAIL, the expertise in robotic and technological rehabilitation of Fondazione Don Carlo Gnocchi, and the literature review. Our proposal aims to facilitate a multi-axial rehabilitation approach customized to meet the unique needs of each individual, with a particular emphasis on utilizing advanced technologies to address the current and future challenges of patient care.

Effects of Multidisciplinary Rehabilitation Enhanced with Neuropsychological Treatment on Post-Acute SARS-CoV-2 Cognitive Impairment (Brain Fog): An Observational Study.

Concentration and memory impairment (named "brain fog") represents a frequent and disabling neuropsychological sequela in post-acute COVID-19 syndrome (PACS) patients. The aim of this study was to assess whether neurocognitive function could improve after a multidisciplinary rehabilitation program enhanced with individualized neuropsychological treatment. A prospective monocentric registry of PACS patients consecutively admitted to our Rehabilitation Unit was created. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive impairment at admission and discharge. A total of sixty-four (64) PACS patients, fifty-six (56) of them with brain fog, were treated with a day-by-day individualized psychological intervention of cognitive stimulation (45 min) on top of a standard in-hospital rehabilitation program. The mean duration of the acute-phase hospitalization was 55.8 ± 25.8 days and the mean in-hospital rehabilitation duration was 30 ± 10 days. The mean age of the patients was 67.3 ± 10.4 years, 66% of them were male, none had a previous diagnosis of dementia, and 66% of the entire sample had experienced severe COVID-19. At admission, only 12% of the patients had normal cognitive function, while 57% showed mild, 28% moderate, and 3% severe cognitive impairment. After psychological treatment, a significant improvement in the MoCA score was found (20.4 ± 5 vs. 24.7 ± 3.7; p < 0.0001) as a result of significant amelioration in the following domains: attention task (p = 0.014), abstract reasoning (p = 0.003), language repetition (p = 0.002), memory recall (p < 0.0001), orientation (p < 0.0001), and visuospatial abilities (p < 0.0001). Moreover, the improvement remained significant after multivariate analysis adjusted for several confounding factors. Finally, at discharge, 43% of the patients with cognitive impairment normalized their cognitive function, while 4.7% were discharged with residual moderate cognitive impairment. In conclusion, our study provides evidence of the effects of multidisciplinary rehabilitation enhanced with neuropsychological treatment on improvement in the cognitive function of post-acute COVID-19 patients.

Characteristics, Components, and Efficacy of Telerehabilitation Approaches for People with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is at the top of the list of non-communicable diseases with related rehabilitation needs. Digital medicine may provide continuative integrated intervention, overcoming accessibility and cost barriers. METHODS: We systematically searched for randomized controlled trials on telerehabilitation (TR) in people with COPD to profile the adopted TR strategies, focusing on TR models and the main rehabilitation actions: monitoring and assessment, decision, and feedback. Additionally, a meta-analysis was run to test the TR effect on functional capacity, dyspnea, and quality of life compared to no intervention (NI) and conventional intervention (CI). RESULTS: Out of the 6041 studies identified, 22 were eligible for the systematic review, and 14 were included in the meta-analyses. Results showed a heterogeneous scenario in terms of the TR features. Furthermore, only a small group of trials presented a comprehensive technological kit. The meta-analysis highlighted a significant effect of TR, especially with the asynchronous model, on all outcomes compared to NI. Moreover, a non-inferiority effect of TR on functional capacity and quality of life, and a superiority effect on dyspnea compared to CI were observed. Finally, the studies suggested a high rate of TR adherence and high safety level. CONCLUSIONS: TR is an effective strategy to increase and maintain functional capacity, breath, and quality of life in people with COPD. However, a consensus on the essential elements and features of this approach needs to be defined, and the effect of long-term maintenance merits further investigation.

Perceived Anxiety, Coping, and Autonomic Function in Takotsubo Syndrome Long after the Acute Event.

BACKGROUND: Anxiety and depressive disorders represent predisposing factors for the autonomic dysfunctions that characterize the acute phase of Takotsubo syndrome (TS). However, there is insufficient data on this relationship after the acute event. The present study aimed at evaluating the psychological and autonomic status of patients with a history of TS. METHODS: Ten TS patients whose acute event occurred at least 1 year prior to the evaluation and nine healthy age- and sex-matched subjects were evaluated. The cardiovascular assessment included a clinical examination, beat-to-beat heart rate monitoring to assess heart rate variability, and a psychological examination using the 16 Personality Factors-C Form (16PF), the Acceptance and Action Questionnaire-II, the Coping Orientations to Problems Experienced (COPE), the Beck Depression Inventory-II, and the State-Trait Anxiety Inventory (STAI). RESULTS: TS patients scored significantly higher on the STAI (i.e., Anxiety Trait), 16PF (i.e., Tension), and COPE (i.e., Transcendental Orientation). TS patients also showed lower heart rate variability. Moreover, a significant inverse correlation was found between sympathetic tone (LF/HF ratio) and coping orientation. CONCLUSIONS: Long after the acute event, TS patients are characterized by elevated anxiety, high tension, and a specific religious coping strategy.

The methodology of a "living" COVID-19 registry development in a clinical context.

OBJECTIVE: The aim of this study was to describe an innovative methodology of a registry development, constantly updated for the scientific assessment and analysis of the health status of the population with COVID-19. STUDY DESIGN AND SETTING: A methodological study design to develop a multi-site, Living COVID-19 Registry of COVID-19 patients admitted in Fondazione Don Gnocchi centres started in March 2020. RESULTS: The integration of the living systematic reviews and focus group methodologies led to a development of a registry which includes 520 fields filled in for 748 COVID-19 patients recruited from 17 Fondazione Don Gnocchi centres. The result is an evidence and experience-based registry, according to the evolution of a new pathology which was not known before outbreak of March 2020 and with the aim of building knowledge to provide a better quality of care for COVID-19 patients. CONCLUSION: A Living COVID-19 Registry is an open, living and up to date access to large-scale patient-level data sets that could help identifying important factors and modulating variable for recognising risk profiles and predicting treatment success in COVID-19 patients hospitalized. This innovative methodology might be used for other registries, to be sure which the data collected is an appropriate means of accomplishing the scientific objectives planned. CLINICAL TRIAL REGISTRATION NUMBER: not applicable.

Telerehabilitation Approaches for People with Chronic Heart Failure: A Systematic Review and Meta-Analysis.

INTRODUCTION: Telerehabilitation (TR) for chronic heart failure (CHF) allows for overcoming distance barriers and reducing exacerbations. However, little is known about TR descriptors, components, and efficacy in CHF. METHODS: This work systematically reviewed the TR strategies of randomized controlled trials in people with CHF. A meta-analysis was run to test its effect on exercise capacity and quality of life compared to no rehabilitation (NI) and conventional intervention (CI). RESULTS: Out of 6168 studies, 11 were eligible for the systematic review, and 8 for the meta-analysis. TR intervention was individual and multidimensional, with a frequency varying from 2 to 5 times per 8-12 weeks. The TR components mainly included an asynchronous model, monitoring/assessment, decision, and offline feedback. A few studies provided a comprehensive technological kit. Minimal adverse events and high adherence were reported. A large effect of TR compared to NI and a non-inferiority effect compared to CI was registered on exercise capacity, but no effects of TR compared to NI and CI on quality of life were observed. CONCLUSIONS: TR for people with CHF adopted established effective strategies. Future interventions may identify the precise TR dose for CHF, technological requirements, and engagement components affecting the patient's quality of life.

Mortality and characteristics of older people dying with COVID-19 in Lombardy nursing homes, Italy: An observational cohort study.

BACKGROUND: The aim of the study was to describe the epidemiological characteristics of Nursing Homes (NHs) residents infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to compute the related case-fatality rate. MATERIALS AND METHODS: The outcomes were mortality and case-fatality rate with related epidemiological characteristics (age, sex, comorbidity, and frailty). RESULTS: During the COVID-19 outbreak lasted from March 1 to May 7, 2020, 330 residents died in Fondazione Don Gnocchi NHs bringing the mortality rate to 27% with a dramatic increase compared to the same period of 2019, when it was 7.5%. Naso/oropharyngeal swabs resulted positive for COVID-19 in 315 (71%) of the 441of the symptomatic/exposed residents tested. The COVID-19 population was 75% female, with a 17% overall fatality rate and sex-specific fatality rates of 19% and 13% for females and males, respectively. Fifty-six percent of deaths presented SARS-CoV-2-associated pneumonia, 15% cardiovascular, and 29% miscellaneous pathologies. CONCLUSION: Patients' complexity and frailty might influence SARS-CoV-2 infection case-fatality rate estimates. A COVID-19 register is needed to study COVID-19 frail patients' epidemiology and characteristics.

Red blood cell distribution width as a novel prognostic marker after myocardial revascularization or cardiac valve surgery.

The red blood cell distribution width (RDW) measures the variability in the size of circulating erythrocytes. Previous studies suggested a powerful correlation between RDW obtained from a standard complete blood count and cardiovascular diseases in both primary and secondary cardiovascular prevention. The current study aimed to evaluate the prognostic role of RDW in patients undergoing cardiac rehabilitation after myocardial revascularization and/or cardiac valve surgery. The study included 1.031 patients with available RDW levels, prospectively followed for a mean of 4.5 ± 3.5 years. The mean age was 68 ± 12 years, the mean RDW was 14.7 ± 1.8%; 492 patients (48%) underwent cardiac rehabilitation after myocardial revascularization, 371 (36%) after cardiac valve surgery, 102 (10%) after valve-plus-coronary artery by-pass graft surgery, 66 (6%) for other indications. Kaplan-Meier analysis and Cox hazard analysis were used to associate RDW with mortality. Kaplan-Meier analysis demonstrated worse survival curves free from overall (log-rank p < 0.0001) and cardiovascular (log-rank p < 0.0001) mortality in the highest RDW tertile. Cox analysis showed RDW levels correlated significantly with the probability of overall (HR 1.26; 95% CI 1.19-1.32; p < 0.001) and cardiovascular (HR 1.31; 95% CI 1.23-1.40; p < 0.001) mortality. After multiple adjustments for cardiovascular risk factors, hemoglobin, hematocrit, C-reactive protein, microalbuminuria, atrial fibrillation, glomerular filtration rate,left ventricular ejection fraction and number of exercise training sessions attended, the increased risk of overall (HR 1.10; 95% CI 1.01-1.27; p = 0.039) and cardiovascular (HR 1.13; 95% CI 1.01-1.34; p = 0.036)mortality with increasing RDW values remained significant. The RDW represents an independent predictor of overall and cardiovascular mortality in secondary cardiovascular prevention patients undergoing cardiac rehabilitation.

Quadriceps muscle group function and after total knee arthroplasty-asystematic narrative update.

BACKGROUND: This article systematically summarizes the present evidences, published in the last 20 years, regarding the pre- and post-operative factors, which may influence recovery of the function of the quadriceps muscle group following total knee arthroplasty (TKA). We following the PRISMA methodology, including meta-analyses and high-level evidence studies (prospective trials, and, when unavailable, retrospective studies). SOURCES OF DATA: Pubmed and Cochrane databases: 582 articles were identified and 54 of them were selected. AREAS OF AGREEMENT: Tourniquets inflated at high pressure exert a detrimental effect on the quadriceps muscle group. Faster quadriceps recovery takes place using mini-invasive approaches, an eight-week rehabilitation period including balance training and the use of nutraceuticals. AREAS OF DISAGREEMENT: Pre-habilitation and pre-operative factors, analgesic methods and different TKA implants. GROWING POINTS AND AREAS TIMELY FOR DEVELOPING RESEARCH: Telerehabilitation seems a cost-effective tool for rehabilitation after TKA. Patients' optimization protocols before TKA should include standardized nutraceuticals intake.

Outcome of total hip and total knee arthroplasty and vitamin D homeostasis.

BACKGROUND: Low levels of vitamin D are common in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA), but it is still unclear whether the outcome of such surgery is related to vitamin D levels. SOURCES OF DATA: Publicly available electronic databases were systematically reviewed to update knowledge about the role of vitamin D in THA and TKA patients, and to appraise the correlation between vitamin D levels before surgery and post-surgical outcomes. Eight studies were included in our review: six employed prospective observational designs, two reported retrospective database interrogations. Six prospective observational studies and two retrospective database interrogations matched inclusion and exclusion criteria. AREAS OF AGREEMENT: Patients undergoing THA and TKA have a high prevalence of hypovitaminosis D. Five of eight studies (62.5%) report a statistically significant association between low vitamin D status and worse outcomes after THA and TKA. AREAS OF CONTROVERSY: Different explanations have been proposed for vitamin D insufficiency, but some authors have questioned the correctness of the methods used to measure the vitamin D levels. GROWING POINTS: A trial focusing on the role of vitamin D supplementation on safety and outcomes of patients undergoing THA and TKA with low vitamin D status is ongoing. AREAS TIMELY FOR DEVELOPING RESEARCH: Further studies should explore the possible causal relationship between vitamin D status and outcomes of THA and TKA and verify the laboratory methods to analyse it.

In-hospital day-by-day systolic blood pressure variability during rehabilitation: a marker of adverse outcome in secondary prevention after myocardial revascularization.

OBJECTIVE: Although it is known that increased visit-to-visit or home day-by-day variability of blood pressure (BP), independently of its average value, results in an increased risk of cardiovascular events, the prognostic value of in-hospital day-by-day BP variability in secondary cardiovascular prevention has not yet been established. METHODS: We studied 1440 consecutive cardiac patients during a cardiovascular rehabilitation program of about 12 days after coronary artery bypass graft (CABG) and/or valve surgery. We measured auscultatory BP at the patient bed in each rehabilitation day twice, in the morning and the afternoon. We correlated SBP variability assessed as standard deviation (SBP-SD) and coefficient of variation (SBP-CoV) of the daily measures with overall mortality, cardiovascular mortality and major adverse cardiocerebrovascular events (MACCEs) after a mean follow-up of 49 months by Cox hazard analysis. RESULTS: In our patients (age 68 ±â€Š11years, 61% hypertensive patients) the ranges of SBP-SD tertiles were: 4.1-9.1, 9.2-11.5 and 11.6-24.5 mmHg. Fifty-five percent of the patients underwent CABG, 33% underwent valve surgery, 12% both CABG and valve surgery. In CABG patients, the highest SBP-SD tertile showed the highest overall mortality, cardiovascular mortality and MACCEs (P < 0.01). Results remained significant after multivariate analysis adjusting for age, sex, mean SBP, BMI, hypertension, hyperlipidaemia, and diabetes. No association between SBP-SD and mortality or MACCEs was found in valve surgery patients. CONCLUSION: In-hospital day-by-day SBP variability predicts mortality and MACCEs in CABG patients, possibly representing a target during rehabilitation and treatment in secondary cardiovascular prevention.

Cardiopulmonary exercise testing for personalized job reintegration after acute cardiovascular attacks: a pilot cross-sectional study.

BACKGROUND: Cardiovascular diseases (CVD), particularly the ischemic heart disease, are a growing public health issue. In addition, the return to work after an acute cardiovascular attack represents a complex challenge. OBJECTIVES: To evaluate utility and safety of cardiopulmonary exercise testing (CPET), particularly performed "on site", to promote a return to work in line with the residual working capacity. METHODS: Fifty-nine workers affected by a major cardiovascular event, aged 18-63 years, have been enrolled between 2015 and 2018. All the patients underwent a cardiopulmonary exercise testing (CPET) in outpatient clinic. Eleven workers also underwent the "on site" CPET, recorded during their working activities. RESULTS: Outpatient clinic CPET outcomes (i.e. normal, mild impairment or moderate/severe impairment of cardiopulmonary function) were associated with the subjective perception of workers' health status after returning to work. The "on site" CPET was found to be safe and reliable to promote a personalized return to work of patients. In 7 out of 11 patients, the values of O2 consumption (VO2) during the working activity were higher than 40% of VO2 max as obtained from laboratory CPET. CONCLUSIONS: This study provides evidence for safety and usefulness of "on site" CPET for a personalized statement of fitness for work. This may facilitate the job retention of patients characterized by a high risk of unnecessary job loss. The use of CPET represents a first step of energy expenditure evaluation associated with specific working tasks.

Prognostic value of frontal QRS-T angle in patients undergoing myocardial revascularization or cardiac valve surgery.

BACKGROUND: An abnormal frontal QRS-T angle (fQRSTa) is associated with increased risk of death in primary and secondary cardiovascular prevention. The aim of this study was to evaluate the fQRSTa prognostic role in patients undergoing myocardial revascularization and/or cardiac valve surgery. METHODS: We enrolled and prospectively followed for 48 ±â€¯26 months 939 subjects with available QRS and T axis data; mean age was 68 ±â€¯12 years, 449 patients (48%) underwent myocardial revascularization, 333 (35%) cardiac valve surgery, 94 (10%) valve plus bypass graft surgery and 63 (7%) cardiac surgery for other cardiovascular (CV) diseases. The ECG variables were collected at the end of the cardiac rehabilitation program and fQRSTa was considered normal if <60°, abnormal if >120°, borderline otherwise. Endpoints were overall and CV mortality. RESULTS: The fQRSTa was normal in 333 patients (36%), borderline in 285 (30%) and abnormal in 321 (34%). Overall (p = 0.012) and cardiovascular (p = 0.007) mortality were significantly higher in patients with abnormal fQRSTa even after adjusting separately for gender, PR-, QTc- intervals, presence of right or left bundle branch block and left atrial volume index. The predictive value was confirmed in patients with stable coronary artery disease (SCAD), not in patients with acute coronary syndrome or valve disease. SCAD patients with abnormal both fQRSTa and QRS axis had higher risk of overall (hazard ratio = 2.9, p < 0.0001) and CV (hazard ratio = 4.4, p < 0.0001) mortality compared with SCAD patients with normal fQRSTa, even after multivariate adjustment for age, gender, ECG intervals, left-ventricle ejection fraction and mass index. CONCLUSIONS: In SCAD patients undergoing myocardial revascularization, abnormal fQRSTa is independent predictor of overall and CV mortality.

Italian consensus conference on guidelines for conservative treatment on lower limb muscle injuries in athlete.

Provide the state of the art concerning (1) biology and aetiology, (2) classification, (3) clinical assessment and (4) conservative treatment of lower limb muscle injuries (MI) in athletes. Seventy international experts with different medical backgrounds participated in the consensus conference. They discussed and approved a consensus composed of four sections which are presented in these documents. This paper represents a synthesis of the consensus conference, the following four sections are discussed: (i) The biology and aetiology of MIs. A definition of MI was formulated and some key points concerning physiology and pathogenesis of MIs were discussed. (ii) The MI classification. A classification of MIs was proposed. (iii) The MI clinical assessment, in which were discussed anamnesis, inspection and clinical examination and are provided the relative guidelines. (iv) The MI conservative treatment, in which are provided the guidelines for conservative treatment based on the severity of the lesion. Furthermore, instrumental therapy and pharmacological treatment were discussed. Knowledge of the aetiology and biology of MIs is an essential prerequisite in order to plan and conduct a rehabilitation plan. Another important aspect is the use of a rational MI classification on prognostic values. We propose a classification based on radiological investigations performed by ultrasonography and MRI strongly linked to prognostic factors. Furthermore, the consensus conference results will able to provide fundamental guidelines for diagnostic and rehabilitation practice, also considering instrumental therapy and pharmacological treatment of MI. Expert opinion, level IV.

Serum uric acid level predicts adverse outcomes after myocardial revascularization or cardiac valve surgery.

Background High levels of serum uric acid have been associated with adverse outcomes in cardiovascular diseases such as myocardial infarction and heart failure. The aim of the current study was to evaluate the prognostic role of serum uric acid levels in patients undergoing cardiac rehabilitation after myocardial revascularization and/or cardiac valve surgery. Design We performed an observational prospective cohort study. Methods The study included 1440 patients with available serum uric acid levels, prospectively followed for 50 ± 17 months. Mean age was 67 ± 11 years; 781 patients (54%) underwent myocardial revascularization, 474 (33%) cardiac valve surgery and 185 (13%) valve-plus-coronary artery by-pass graft surgery. The primary endpoints were overall and cardiovascular mortality while secondary end-points were combined major adverse cardiac and cerebrovascular events. Results Serum uric acid level mean values were 286 ± 95 µmol/l and elevated serum uric acid levels (≥360 µmol/l or 6 mg/dl) were found in 275 patients (19%). Overall mortality (hazard ratio = 2.1; 95% confidence interval: 1.5-3.0; p < 0.001), cardiovascular mortality (hazard ratio = 2.0; 95% confidence interval: 1.2-3.2; p = 0.004) and major adverse cardiac and cerebrovascular events rate (hazard ratio = 1.5; 95% confidence interval: 1.0-2.0; p = 0.019) were significantly higher in patients with elevated serum uric acid levels, even after adjustment for age, gender, arterial hypertension, diabetes, glomerular filtration rate, atrial fibrillation and medical therapy. Moreover, strong positive correlations between serum uric acid level and probability of overall mortality ( p < 0.001), cardiovascular mortality ( p < 0.001) and major adverse cardiac and cerebrovascular events ( p = 0.003) were found. Conclusions Serum uric acid levels predict mortality and adverse cardiovascular outcome in patients undergoing myocardial revascularization and/or cardiac valve surgery even after the adjustment for age, gender, arterial hypertension, diabetes, glomerular filtration rate and medical therapy.

Anxiety disorders and stressful events in Takotsubo syndrome.

BACKGROUND: Anxiety disorders are more common in Takotsubo syndrome (TS) than in acute coronary syndrome patients. The aim of this study was to investigate whether pre-existing anxiety disorders predispose to TS triggered by exclusively emotional stressful events. METHODS: Triggering events were compared in 58 TS patients with and without pre-existing anxiety disorders; clinical, electrocardiographic and echocardiographic data were also collected. RESULTS: Thirty-one (53%) patients had a previous history of anxiety disorders. The exclusively emotional stressful event-rate was higher in TS patients with pre-existing anxiety disorder (74% vs. 30%, p = 0.001), while TS caused by an undetermined trigger were significantly higher in patients without anxiety disorders (33% vs. 10%, p = 0.027). Moreover, in TS patients without a previous history of anxiety disorders, a trend of higher prevalence of physical events was found (16% vs. 37%, p = 0.07). CONCLUSIONS: In patients with pre-existing anxiety disorders, TS was predominantly triggered by exclusively emotional stressful events, thereby suggesting a possible relationship between anxiety and emotional cardiac frailty in TS patients.