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Objective: The purpose of this study was to explore microvascular function impairment using first-pass cardiovascular magnetic resonance (CMR) in patients with Takotsubo syndrome (TS). Moreover, we explored myocardial microcirculation in patients with TS and related this to demographic data, cardiovascular risk factors, clinical parameters, cardiac biomarkers, and cardiac function., Methods: This retrospective study performed CMR first-pass perfusion scans in 42 consecutive patients with TS (37 females, 70.6 ± 9.4 years). Moreover, we included 44 sex- and age-matched healthy controls (33 females, 66.4 ± 10.5 years). CMR-derived myocardial microcirculation function was analyzed and compared between TS patients and controls., Results: Compared to age-, sex-, and cardiovascular risk factors-matched control group, TS patients demonstrated a lower perfusion index (PI) (0.140 ± 0.060 vs. 0.182 ± 0.056, p = 0.001). In multivariable analysis with adjustment for demographic data and cardiovascular risk factors, an impairment in PI was independently associated with left ventricle ejection fraction (β coefficient = 3.793, p = 0.001) and T2 mapping (β coefficient = -4.316, p = 0.001)., Conclusion: TS patients exhibited myocardial microvascular dysfunction, which was non-invasively assessed using first-pass CMR. This impaired myocardial microvascular function was found to be independently associated with left ventricular ejection fraction and myocardial edema., Key Points: Question Can cardiovascular magnetic resonance (CMR) cardiac MR first-pass perfusion help to better understand Takotsubo pathophysiology by exploring microvascular impairment? Findings CMR first-pass perfusion revealed significant microvascular dysfunction during the acute phase of Takotsubo syndrome, independently associated with left ventricular ejection fraction and myocardial edema. Clinical relevance Identifying an abnormal microvascular network using non-invasive biomarkers could enhance risk stratification and guide tailored management during the acute phase of Takotsubo syndrome., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is the corresponding Author. Conflict of interest: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: No complex statistical methods were necessary for this paper. Informed consent: Written informed consent was waived by the Institutional Review Board. Ethical approval: Institutional Review Board approval was obtained. Study subjects or cohorts overlap: Some study subjects or cohorts have been previously reported in our previous studies ( https://doi.org/10.1016/j.ijcard.2022.11.021 ; https://doi.org/10.1016/j.ejrad.2023.110706 ; https://doi.org/10.1177/08465371211042497 ; https://doi.org/10.1097/RTI.0000000000000761 ). Methodology: Retrospective Cross-sectional study Performed at one institution, (© 2025. The Author(s), under exclusive licence to European Society of Radiology.)

The purpose of this study was to explore the impact of papillary muscle (PPM) infarction on left atrial and ventricular strain parameters in patients with non-anterior ST-segment elevation myocardial infarction (NA-STEMI) using cardiovascular magnetic resonance (CMR). This retrospective study performed CMR scans on 88 consecutive patients with NA-STEMI (68 males, 65 ± 10.05 years). Among them, 30 demonstrated PPM infarction (25 males, 67.12 ± 9.49 years), defined as late gadolinium enhancement (LGE) in a papillary muscle head in two contiguous LGE CMR slices, and confirmed on the long-axis LGE CMR slices. Atrial and ventricular strain were analyzed by CMR feature tracking with dedicated post-processing software. Patients with PPM infarction were older (p = 0.001), with lower left ventricular ejection fraction (p = 0.040), higher indexed left ventricular end-diastolic volume (p = 0.020), and end-systolic volume (p = 0.044) compared to patients without LGE in the papillary muscle. Additionally, patients with PPM infarction showed impaired reservoir strain, booster strain, global longitudinal strain (GLS), and higher LGE extent compared to NA-STEMI patients without PPM involvement (p = 0.001, p = 0.004, p = 0.001, and p = 0.003, respectively). In multivariable analysis, GLS, global radial strain, reservoir strain, and booster strain parameters were the only independent determinants of PPM infarction (p = 0.001, p = 0.041, p = 0.002, and p = 0.027, respectively). The presence of PPM infarction assessed by CMR is independently linked to atrial and ventricular strain impairment in patients with NA-STEMI., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Competing Interests: Funding Support and Author Disclosures Dr Corsini has received consulting fees and lecture fees from Algorithm, Amarin, Amgen, DOC, Fidia, Novartis, Merck Sharp & Dohme, Recordati Spa, Sanofi, Servier, and Viatris; and has received grant support from Daiichi-Sankyo. The other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

We report the case of an athlete who, despite facing the challenges of laryngectomy, underwent a comprehensive cardiopulmonary exercise test to assess both his ability to participate in sports and his cardiopulmonary fitness. We not only highlight the individualized approach to sports assessment in a challenging medical context but also emphasize the feasibility of employing cardiopulmonary testing in evaluating subjects in unusual settings.

Background: Worsening Heart Failure (WHF) is associated with adverse prognosis. Identifying novel prognostic markers in WHF is crucial. Gait speed (GS), a validated frailty index, is an easily obtainable parameter that may aid in reclassifying the risk of HF patients. We assessed the independent prognostic role of GS in WHF patients., Methods: We studied 171 patients with chronic HF with worsening congestion symptoms and inadequate response to standard therapies, requiring intravenous diuretic treatment. The primary outcome was a composite of all-cause mortality or HF hospitalization. We assessed the association and the incremental value of GS, as compared to other clinical confounders, with the primary outcome., Results: The mean age was 76±11 years, 66 % were male, median BNP was 481 pg/ml, and median ejection fraction was 40 %. Over a median follow-up of 11.3 months, 71 events occurred. Lower GS was significantly associated with a higher risk of events (HR of 4.03, 95 % CI 2.25-7.21), along with neutrophil to lymphocyte ratio, BNP, QRS duration, natremia, and previous myocardial infarction. When added to the MAGGIC risk score and the other significant confounders identified, GS significantly enhanced the model risk prediction (Harrell's C-index 0.75 vs 0.71, p < 0.001). At Classification And Regression Tree analysis, GS≤0.8 m/s was the first parameter to be considered to risk stratify the population., Conclusions: GS, an easily obtainable marker of frailty, may contribute to improve the risk stratification of patients with WHF., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Amyotrophic lateral sclerosis (ALS) is known to be associated with varying degrees of autonomic and cardiovascular dysfunction. Recent case reports showed that ALS may be linked to Takotsubo syndrome (TTS). We assessed the frequency of TTS in an incident ALS cohort from Sardinia, Italy, and investigated the relationship of TTS with ALS course., Methods: We retrospectively examined a 10-year (2010-2019) incident cohort of ALS patients of Sardinian ancestry, reported TTS frequency and patients' clinical characteristics. Following, we checked for TTS among patients with ALS onset after 2019 and focused on the same features as for the incident cohort., Results: Our incident cohort included 344 ALS patients and 5 of them (1.45%) developed TTS. All were female and their median onset age was 71.5 years (IQR 62.75-77). Two patients had spinal and three bulbar onset, though all patients had bulbar involvement and were at an advanced stage of disease (ALSFRS ≤ 25, King's ≥ 3) at TTS diagnosis. We identified a potential TTS trigger in three patients (hospitalization for PEG placement, pneumonia). Among patients who had ALS onset after 2019, we identified a further TTS case and described it., Conclusion: TTS is not a rare condition in ALS. Female sex, bulbar involvement, and later age of disease onset may be important risk factors for developing this cardiac condition and a physical or psychological trigger is often observed. Despite autonomic dysfunction in ALS has been already demonstrated, the precise physiopathological mechanism underlying TTS needs to be further clarified., Competing Interests: Declarations. Conflicts of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethical approval: The study was approved by the local Institutional Review Board and conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments., (© 2024. The Author(s).)

Positive remodeling (PR) is an atherosclerotic plaque feature defined as an increase in arterial caliber at the level of an atheroma, in response to increasing plaque burden. The mechanisms that lead to its formation are incompletely understood, but its role in coronary atherosclerosis has major clinical implications. Indeed, plaques with PR have elevated risk of provoking acute cardiac events. Hence, PR figures among the high-risk plaque features that cardiac imaging studies should report. This review aims to provide an overview of the current literature on coronary PR. It outlines the pathophysiology of PR, the different techniques used to assess its presence, and the imaging findings associated to PR, on both noninvasive and invasive studies. This review also summarizes clinical observations, trials, and studies, focused on the impact of PR on clinical outcome., Competing Interests: None.

Background: Few data are available on long-term drug therapy and its potential prognostic impact after Takotsubo syndrome (TTS). Aim of the study is to evaluate clinical characteristics and long-term outcome of TTS patients on Renin Angiotensin system inhibitors (RASi)., Methods: TTS patients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Median follow-up was 31 (Interquartile range 12-56) months. Comparison of RASi treated vs. untreated patients was performed within the overall population and after 1:1 propensity score matching for age, sex, comorbidities, type of trigger and in-hospital complications., Registration: clinicaltrials.gov, NCT04361994, https://clinicaltrials.gov/study/NCT04361994 RESULTS: Of the 2453 TTS patients discharged alive, 1683 (68%) received RASi therapy. Patients with RASi were older (age 71 ± 11 vs 69 ± 13 years, P = .01), with higher prevalence of hypertension (74% vs 53%, P < .01) and diabetes (19% v s15%, P = .01), higher admission left ventricular ejection fraction (LVEF) (41 ± 11% vs 39 ± 12%, P < .01) and lower rates of in-hospital complications (18.9% vs 29.6%, P < .01). At multivariable analysis, RASi therapy at discharge was independently associated with lower mortality (HR 0.63, 95% CI 0.45-0.87, P < .01). Survival analysis showed that at long term, patients treated with RASi had lower mortality rates in the overall cohort (log-rank P = .001). However, this benefit was not found among patients treated with RASi in the matched cohort (log-rank P = .168). Potential survival benefit of RASi were present, both in the overall and matched cohort, in 2 subgroups: patients with admission LVEF ≤ 40% (HR 0.54 95% CI 0.38-0.78, P = .001; HR 0.59, 95% CI 0.37-0.95, P = .030) and diabetes (HR 0.41, 95% CI 0.23-0.73, P = .002; HR 0.41, 95% CI 0.21-0.82, P = .011)., Conclusions: Long-term therapy with RASi after a TTS episode was not associated with lower mortality rates at propensity score analysis. However, potential survival benefit can be found among patients with admission LVEF ≤ 40% or diabetes., Competing Interests: Conflict of interest None reported., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: During exercise stress echocardiography (ESE), there are patients with normal left ventricular ejection fraction (LVEF) who paradoxically develop reduced LVEF during exercise despite absence of coronary artery disease (CAD) and a significant hypertensive response. This study sought to describe the clinical features and outcomes of this population., Methods: Among ESEs performed between 2003 and 2022, patients without CAD by angiogram within 90 days of ESE and resting LVEF ≥50% with a ≥5% LVEF decrease during ESE were included. Outcomes assessed were all-cause mortality, heart failure (HF) hospitalization, and atrial fibrillation (AF). Kaplan-Meier and Cox regression methods were used to analyze time-to-event outcomes., Results: Among 213,643 ESE, 134 patients met the eligibility criteria. The mean age of the population was 66 ± 10 years, 76% were women, and 16% had AF at baseline. Mean LVEF was 58% ± 4% at rest and 43% ± 4% at peak stress. Stress ECG met the criteria for ischemia in 14% of these patients. The 10-year estimated incidence of HF hospitalization was 17.6% (95% CI, 9.0%-26.2%). Among the subgroup without AF at baseline, the 10-year estimated incidence of developing AF was 23.4% (95% CI, 13.4%-33.4%). The 10-year estimated incidence of all-cause mortality was 12.9% (95% CI, 5.5%-20.3%), with 89% of deaths occurring due to noncardiovascular causes., Conclusion: Patients with exercise-induced reduction in LVEF in the absence of obstructive CAD have a high incidence of HF hospitalizations and AF. The underlying pathophysiology of this disease process needs to be further investigated., Competing Interests: Conflicts of Interest None., (Copyright © 2024 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to explore the impact of pericardial T1 mapping as a potential supportive non-contrast cardiovascular magnetic resonance (CMR) parameter in the diagnosis of acute pericarditis. Additionally, we investigated the relationship between T1 mapping values in acute pericarditis patients and their demographic data, cardiovascular risk factors, clinical parameters, cardiac biomarkers, and cardiac function., Method: This retrospective study included CMR scans in 35 consecutive patients with acute pericarditis (26 males, 45.54 ± 23.38 years). Moreover, we included 17 sex- and age-matched healthy controls (12 males, mean age 47.78 ±19.38 years). CMR-derived pericardial T1 mapping values, which included all pericardial structures within the pericardial layers-encompassing both pericardial effusion and pericardial layer thickness-were analyzed and compared between acute pericarditis patients and controls., Results: Compared to the matched control group, acute pericarditis patients demonstrated significantly lower pericardial T1 mapping values (2137 ms ± 519 vs. 3268 ms ± 362, p = 0.001). In the multivariable analysis, the pericardial T1 mapping value was independently associated with the severity of pericardial late gadolinium enhancement (LGE) (β coefficient = -3.271, p = 0.003). The receiver operating characteristic curve analysis showed that the diagnostic performance of pericardial T1 mapping in discriminating acute pericarditis patients was excellent, with an area under the curve of 0.97 (95% CI = 0.94-0.98), using a threshold of 2862.5 ms., Conclusions: Pericardial T1 mapping values could serve as an additional non-contrast CMR parameter for identifying patients with acute pericarditis, demonstrating an independent association with the severity of pericardial LGE.

The absence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is commonly used to distinguish takotsubo syndrome (TTS) from other myocardial diseases. However, case series have reported the presence of LGE in TTS. This study aimed to summarize the evidence on the frequency of LGE in TTS and identify potential variables that may influence the detection of LGE. Electronic databases were systematically searched for studies reporting LGE frequency in patients with TTS. The overall frequency was estimated using the inverse variance method and a random-effects model for a single proportion. Factors influencing LGE detection were analyzed. Of 490 studies screened, 21 were included (703 patients, 90% women). The estimated overall frequency of LGE was 22.4% (95% confidence interval [CI] 8.7% to 39.6%). In patients with TTS who underwent CMR within 3 days of symptom occurrence, the frequency of LGE was 40.7% (95% CI 18.8% to 64.5%), which was significantly higher than in those who performed CMR after 3 days (3.9%, p <0.010). The sensitivity threshold used in the imaging protocols had a statistically significant impact on the frequency of LGE detection (p = 0.030). A total of 10 studies performed a follow-up CMR after at least 3 months, reporting a frequency of LGE of 1.7% (95% CI 0.0% to 8.9%). In conclusion, published studies report the presence of LGE in TTS at presentation in a significant proportion of patients. However, its detection is strongly influenced by the duration between symptom onset and CMR acquisition and by the sensitivity threshold used for the imaging protocol. LGE is rarely present at follow-up., Competing Interests: Declaration of competing interest The authors have no competing interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: With the growing older adult population, the European Union emphasizes the need to promote research in healthy aging trough multidisciplinary and innovative approaches, including the integration of advanced technologies like virtual reality (VR) in cognitive rehabilitation. This reflects the increasing awareness of the importance of addressing challenges related to neurodegenerative diseases in the older adult population. Our study aims to present a protocol that will assess the feasibility and provide a preliminary measure of effectiveness for an intervention using immersive CR technology for cognitive remediation (CR) in individuals with Mild Cognitive Impairment (MCI)., Methods: A feasibility randomized controlled clinical study will involve 30 individuals who are over 65 years old, both sex, who meet the diagnostic criteria for MCI from the University Hospital of Cagliari, randomly assigned to either the experimental condition or control group. Both groups will continue to receive standard pharmacological therapy. The experimental group will undergo a 3-months cognitive remediation program using fully immersive VR with two sessions per week. Each session will last a maximum of 60 min and will be supervised by expert health professionals. In contrast, the control group will continue with standard care. The intervention program will be carried out by s psychiatric rehabilitation technicians and speech therapists, emphasizing a comprehensive framework aligned with healthcare needs. Feasibility will be assessed based on tolerability, including dropout rates and acceptability, which considers the proportion of recruited participants among those considered eligible and on side effects and level of satisfaction. The preliminary measures of effectiveness will be evaluated on quality of life, cognitive functions, biological and social rhythms, depressive symptoms and anxiety., Results: The trial findings will be submitted for publication in international peer-reviewed journals and shared at international meetings and conferences., Discussion: This study aiming to assess the feasibility and preliminary effectiveness of a fully immersive VR/CR program for MCI in order to give data for a subsequent confirmatory trial. The results of the pilot RCT are expected to significantly contribute to research on the prevention of neurocognitive degeneration, with a specific emphasis on enhancing the application of technologies. The strengths of this work are the high technological innovation program for mental health treatments for healthy aging and multidisciplinary approach emphasizing a holistic framework aligned with health needs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Perra, Primavera, Leonetti, Montisci, Chessa, Scuteri, Cossu, Nardi, Valmaggia, Galetti, De Lorenzo, Sancassiani and Carta.)

Background: Alexithymia, a predictor in chronic illnesses, like cardiovascular and bipolar disorder (CD-BD), could be improved with a virtual reality (VR) cognitive remediation program. This secondary analysis of a previous randomized controlled trial (RCT) evaluates alexithymia improvement and its factors in an experimental group versus a control group, exploring extensions to individuals with comorbid non-psychiatric chronic conditions. Methods: A feasibility cross-over RCT (ClinicalTrials.gov NCT05070065) enrolled individuals aged 18-75 with mood disorders (BD, DSM-IV), excluding those with relapses, epilepsy, or severe eye conditions due to potential risks with VR. Alexithymia levels were measured using the Toronto Alexithymia Scale with 20 items (TAS-20). Results: The study included 39 individuals in the experimental group and 25 in the control group, with no significant age or sex differences observed. Significantly improved alexithymia scores were noted in the experimental group compared to controls (F = 111.9; p < 0.0001) and in subgroups with chronic non-psychiatric comorbidities (F = 4.293, p = 0.048). Scores were particularly improved for difficulty in identifying feelings (F = 92.42; p < 0.00001), communicating feelings (F = 61.34; p < 0.00001), and externally oriented thinking (F = 173.12; p < 0.00001). Conclusions: The findings highlight alexithymia enhancement in BD, even with comorbid non-psychiatric chronic diseases. Given its impact on BD progression and related conditions, like CD, developing and evaluating VR-based tools in this context is suggested by these findings.

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., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: This cross-sectional analysis intends to evaluate trend and outlook of industry clinical research in Italy regarding dermatology and its prospects for the next few years., Methods: A computerized search of ClinicalTrial.gov database was carried out considering the 20-year period 2003-2022 using the following string: "Skin Diseases OR Skin cancer OR Skin Neoplasms OR Skin Infection OR Skin Lesion OR Skin Ulcer OR Skin Laxity OR Skin toxicity OR Dermatologic Complication OR Skin abnormalities"., Results: During the last 20 years 690 Industry Clinical Trials (IndCTs) were conducted in Italy regarding dermatological investigations, almost entirely funded by non-Italian pharmaceutical companies, involving 4497 centers, and recruiting an average of 13.0 subjects per site. The number of controlled and randomized studies has grown quite regularly and in the last 5 years they represented 79.6% of IndCTs initiated. Countries most frequently sharing with Italy international protocols were Spain (75.0%), Germany (71.8%), France (68.5%), the USA (67.4%), and the UK (54.8%). These data point to a historical involvement of Italy in dermatology IndCTs lower than in the major European countries. However, the war in Ukraine has deprived IndCTs of the contribution of Russia, Ukraine, and Belarus, meaning a mean of about 40 new IndCTs per year in a population of 200 million inhabitants. In contrast, many indicators point to Italy as a country with potential in dermatology wider than used in the past: an efficient health care system accessible to any citizen or resident, 4.6 million dermatological interventions per year, low density of IndCTs concerning dermatology, good production of scientific papers in indexed medical journals, relatively low cost of services and labour and geopolitical stability., Conclusions: The European Clinical Trials Information System's (CTIS), mandatory for the EU member states since early 2023 allows common, simplified, and harmonized regulatory procedures over the life cycle of clinical trials in Europe (EMA, 2023) and plays in favor of Italy's greater competitiveness in clinical research.

Aims: The identification of subjects at higher risk for incident heart failure (HF) with preserved ejection fraction (EF) suitable for more intensive preventive programmes remains challenging. We applied phenomapping to the DAVID-Berg population, comprising subjects with preclinical HF, aiming to refine HF risk stratification., Methods: The DAVID-Berg study prospectively enrolled 596 asymptomatic outpatients with EF > 40% with hypertension, diabetes mellitus or known cardiovascular disease. In this cohort, we performed an unsupervised cluster analysis on 591 patients, including clinical, laboratory, electrocardiographic and echocardiographic parameters. We tested the association between each cluster and a composite outcome of HF/death., Results: The median age was 70 years, 55.5% were males and the median EF was 61.0%. Phenomapping provided three different clusters. Subjects in Cluster 3 were the oldest and had the highest prevalence of atrial fibrillation, the lowest estimated glomerular filtration rate (eGFR), the highest N-terminal pro-brain natriuretic peptide (NT-proBNP) and the largest left atrium. During a median follow-up of 5.7 years, 13.4% of subjects experienced HF/death events (N = 79). Compared with Clusters 1 and 2, Cluster 3 had the worst prognosis (log-rank test: Cluster 3 vs. 1 P < 0.001; Cluster 3 vs. 2 P = 0.008). Cluster 3 was associated with a risk of HF/death 2.5 times higher than Cluster 1 [adjusted hazard ratio (HR) = 2.46, 95% confidence interval (CI) 1.24-4.90]., Conclusions: Based on phenomapping, older patients with lower kidney function and worse diastolic function might represent a subset of preclinical HF with EF > 40% who deserve more efforts to prevent clinical HF., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: This work aimed to derive a machine learning (ML) model for the differentiation between ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM) on non-contrast cardiovascular magnetic resonance (CMR)., Methods: This retrospective study evaluated CMR scans of 107 consecutive patients (49 ICM, 58 NICM), including atrial and ventricular strain parameters. We used these data to compare an explainable tree-based gradient boosting additive model with four traditional ML models for the differentiation of ICM and NICM. The models were trained and internally validated with repeated cross-validation according to discrimination and calibration. Furthermore, we examined important variables for distinguishing between ICM and NICM., Results: A total of 107 patients and 38 variables were available for the analysis. Of those, 49 were ICM (34 males, mean age 60 ± 9 years) and 58 patients were NICM (38 males, mean age 56 ± 19 years). After 10 repetitions of the tenfold cross-validation, the proposed model achieved the highest area under curve (0.82, 95% CI [0.47-1.00]) and lowest Brier score (0.19, 95% CI [0.13-0.27]), showing competitive diagnostic accuracy and calibration. At the Youden's index, sensitivity was 0.72 (95% CI [0.68-0.76]), the highest of all. Analysis of predictions revealed that both atrial and ventricular strain CMR parameters were important for the identification of ICM patients., Conclusion: The current study demonstrated that using a ML model, multi chamber myocardial strain, and function on non-contrast CMR parameters enables the discrimination between ICM and NICM with competitive diagnostic accuracy., Clinical Relevance Statement: A machine learning model based on non-contrast cardiovascular magnetic resonance parameters may discriminate between ischemic and non-ischemic cardiomyopathy enabling wider access to cardiovascular magnetic resonance examinations with lower costs and faster imaging acquisition., Key Points: • The exponential growth in cardiovascular magnetic resonance examinations may require faster and more cost-effective protocols. • Artificial intelligence models can be utilized to distinguish between ischemic and non-ischemic etiologies. • Machine learning using non-contrast CMR parameters can effectively distinguish between ischemic and non-ischemic cardiomyopathies., (© 2024. The Author(s).)

Pregnancy represents a stress test for every woman's cardiovascular (CV) system, and a pre-existing maternal unfavorable cardio-metabolic phenotype can uncover both adverse pregnancy outcomes and the subsequent development of cardiovascular disease (CVD) risk factors during and after pregnancy. Moreover, the maternal cardiac and extracardiac environment can affect offspring's cardiovascular health through a complex mechanism called developmental programming, in which fetal growth can be influenced by maternal conditions. This interaction continues later in life, as adverse developmental programming, along with lifestyle risk factors and genetic predisposition, can exacerbate and accelerate the development of CV risk factors and CVD in childhood and adolescence. The aim of this narrative review is to summarize the latest evidences regarding maternal-fetal dyad and its role on primordial, primary and secondary CV prevention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to investigate the base-to-apex gradient strain pattern as a noncontrast cardiovascular magnetic resonance (CMR) parameter in patients with Takotsubo cardiomyopathy (TTC) and determine whether this pattern may help discriminate TTC from patients with anterior myocardial infarction (AMI)., Materials and Methods: A total of 80 patients were included in the analysis: 30 patients with apical ballooning TTC and 50 patients with AMI. Global and regional ventricular function, including longitudinal (LS), circumferential (CS), and radial strain (RS), were assessed using CMR. The base-to-apex LS, RS, and CS gradients, defined as the peak gradient difference between averaged basal and apical strain, were calculated., Results: The base-to-apex RS gradient was impaired in TTC patients compared with the AMI group (14.04 ± 15.50 vs. -0.43 ± 11.59, P =0.001). Conversely, there were no significant differences in the base-to-apex LS and CS gradients between the AMI group and TTC patients (0.14 ± 2.71 vs. -1.5 ± 3.69, P =0.054: -0.99 ± 6.49 vs. ±1.4 ± 5.43, P =0.47, respectively). Beyond the presence and extension of LGE, base-to-apex RS gradient was the only independent discriminator between TTC and AMI (OR 1.28; 95% CI 1.08, 1.52, P =0.006) in multivariate logistic regression analysis., Conclusion: The findings of this study suggest that the pattern of regional myocardial strain impairment could serve as an additional noncontrast CMR tool to refine the diagnosis of TTC. A pronounced base-to-apex RS gradient may be a specific left ventricle strain pattern of TTC., Competing Interests: The authors declare no conflicts of interests., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Patent foramen ovale (PFO) is a prevalent congenital cardiac anomaly associated with a persistent opening between the atrial septum, allowing communication between the left and right atria. Despite often being asymptomatic, PFO can lead to various clinical presentations, including cryptogenic stroke and other embolic events. Transient visual disturbances, alterations in the visual field, migraine with aura, impaired eye movement and endogenous eye infections may prompt patients to seek ophthalmological consultation. Understanding these diverse clinical scenarios is crucial for early detection, appropriate management and mitigating the morbidity burden associated with PFO. This narrative review aims at examining the spectrum of clinical presentations of ocular pictures associated with PFO. The pathophysiology, diagnosis and treatment methods for PFO will be described, emphasizing the importance of a multidisciplinary approach involving ophthalmologists, cardiologists, neurologists and imaging specialists. In the future, prospective studies and clinical trials are warranted to provide further insights into the preventive role and optimal therapeutic strategies for managing PFO-related ocular complications, ultimately guiding clinical decision making and optimizing patient care.

Cardiac magnetic resonance (CMR) is commonly employed to confirm the diagnosis of acute myocarditis (AM). However, the impact of atrial and ventricular function in AM patients with preserved ejection fraction (EF) deserves further investigation. Therefore, the aim of this study was to explore the incremental diagnostic value of combining atrial and strain functions using CMR in patients with AM and preserved EF. This retrospective study collected CMR scans of 126 consecutive patients with AM (meeting the Lake Louise criteria) and with preserved EF, as well as 52 age- and sex-matched control subjects. Left atrial (LA) and left ventricular (LV) strain functions were assessed using conventional cine-SSFP sequences. In patients with AM and preserved EF, impaired ventricular and atrial strain functions were observed compared to control subjects. These impairments remained significant even in multivariable analysis. The combined model of atrial and ventricular functions proved to be the most effective in distinguishing AM patients with preserved ejection fraction from control subjects, achieving an area under the curve of 0.77 and showing a significant improvement in the likelihood ratio. These findings suggest that a combined analysis of both atrial and ventricular functions may improve the diagnostic accuracy for patients with AM and preserved EF.

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.

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.

We propose a novel method for assessing metabolic flexibility (MF) through indirect calorimetry. A total of twenty healthy volunteers (10 females; 10 males) aged 45-65 were categorized into a Low-Intensity activity group (LI, 0-1 session of 1 h per week) and a High-Intensity activity group (HI, 5-6 sessions of 2 h per week). Volunteers underwent a stepwise exercise test on a cycle ergometer, connected to a calorimeter, to examine respiratory gas exchange to evaluate peak fatty acid Oxidation (PFO) and peak carbohydrate oxidation (PCO). Circulating peroxisome proliferator-activated receptor α (PPARα) biomarkers, docosahexaenoic acid/eicosapentaenoic acid (DHA/EPA) ratio and N -oleoylethanolamine (OEA), and the endocannabinoid- 2-arachidonoylglycerol (2-AG), were evaluated. We developed two MF parameters: the MF index (MFI), calculated by the product of PFO normalized per kg of fat-free mass (FFM) and the percentage of VO 2max at PFO, and the peak energy substrates' oxidation (PESO), computed by summing the kilocalories from the PFO and PCO, normalized per kg FFM. The MFI and PESO were significantly different between the HI and LI groups, showing strong correlations with the circulating bioactive substances. Higher DHA/EPA ratio ( p ≤ 0.05) and OEA ( p ≤ 0.01), but lower 2-AG levels ( p ≤ 0.01) were found in the HI group. These new parameters successfully established a functional link between MF and the balance of PPARα/endocannabinoid systems.

Background and Aims: Several studies have shown that endothelial dysfunction plays a role in the pathogenesis of Takotsubo syndrome (TTS). Given the potential benefit of statin therapy on endothelial dysfunction, we hypothesized that such treatment could improve outcome. Aim of our study was to evaluate clinical characteristics and outcome of TTS patients treated with statin therapy., Methods: Patients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Demographic data, clinical features and drug therapy at discharge were recorded. Primary study outcome was the occurrence of all-cause death at follow-up., Results: Study population included 2429 consecutive TTS patients: 1293 (53.2%) discharged on statin and 1136 (46.8%) without statin. Patients with statin were older (age 72 ± 11 vs 69 ± 13 years, p < 0.001), with higher prevalence of hypertension (74.3% vs 60.3%, p < 0.001), diabetes (21.1% vs 14.7%, p < 0.001), dyslipidemia (56.1% vs 23.3%, p < 0.001), history of coronary artery disease (13.3% vs 6.3%, p < 0.001) and lower rates of in-hospital complications (14.7% vs 19.3%, p = 0.003). Survival analysis showed similar mortality rates between groups (log rank p = 0.803). At univariable analysis, statin therapy at discharge was not associated with lower mortality (HR: 0.97, 95% CI 0.74-1.26, p = 0.803). At multivariable analysis age (HR: 1.06 95% CI 1.04-1.08, p < 0.001), male sex (HR: 1.83, 95% CI 1.20-2.80, p = 0.005), diabetes (HR: 2.55, 95% CI 1.83-3.54 p < 0.001), malignancies (HR: 2.41, 95% CI 1.68-3.44, p < 0.001) and physical trigger (HR: 2.24, 95% CI 1.62-3.10, p < 0.001) were associated with increased mortality., Conclusions: Statin therapy after a TTS event was not associated with better prognosis at follow-up., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Artificial intelligence (AI) is rapidly being applied to the medical field, especially in the cardiovascular domain. AI approaches have demonstrated their applicability in the detection, diagnosis, and management of several cardiovascular diseases, enhancing disease stratification and typing. Cardiomyopathies are a leading cause of heart failure and life-threatening ventricular arrhythmias. Identifying the etiologies is fundamental for the management and diagnostic pathway of these heart muscle diseases, requiring the integration of various data, including personal and family history, clinical examination, electrocardiography, and laboratory investigations, as well as multimodality imaging, making the clinical diagnosis challenging. In this scenario, AI has demonstrated its capability to capture subtle connections from a multitude of multiparametric datasets, enabling the discovery of hidden relationships in data and handling more complex tasks than traditional methods. This review aims to present a comprehensive overview of the main concepts related to AI and its subset. Additionally, we review the existing literature on AI-based models in the differential diagnosis of cardiomyopathy phenotypes, and we finally examine the advantages and limitations of these AI approaches.

Background: Twiddler syndrome (TS) is a complication of cardiac implantable electronic device (CIED) implantation, caused by the deliberate or unconscious manipulation of the device by the patient himself, which results in dislocation of the leads by retraction towards the subcutaneous pocket., Case Summary: This report describes two clinical cases that occurred in our centre, for which two different solutions were successfully implemented. In the first case, a complete removal of the stimulation system was performed, and a leadless pacemaker (PM; Medtronic Micra VR) was implanted. In the second case, the patient underwent a revision procedure. The PM was disconnected, and the electrodes were debrided, a submuscular pocket for the PM was created, and at the end of the procedure, the PM was anchored to the pectoralis major., Discussion: Twiddler syndrome is a not so rare and serious complication of CIED implantation, leading to device malfunctioning and higher risk of infection of the pocket due to multiple re-interventions. In these two cases, different surgical solutions were performed, both resulting to be effective to solve the effects of TS., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: Disclosures None.

Aims: To assess the influence of tobacco on acute and long-term outcomes in Takotsubo syndrome (TTS)., Methods: Patients with TTS from the international multicenter German Italian Spanish Takotsubo registry (GEIST) were analyzed. Comparisons between groups were performed within the overall cohort, and an adjusted analysis with 1:1 propensity score matching was conducted., Results: Out of 3,152 patients with TTS, 534 (17%) were current smokers. Smoker TTS patients were younger (63 ± 11 vs. 72 ± 11 years, p  < 0.001), less frequently women (78% vs. 90%, p  < 0.001), and had a lower prevalence of hypertension (59% vs. 69%, p  < 0.01) and diabetes mellitus (16% vs. 20%, p  = 0.04), but had a higher prevalence of pulmonary (21% vs. 15%, p  < 0.01) and/or psychiatric diseases (17% vs. 12%, p  < 0.01). On multivariable analysis, age less than 65 years [OR 3.85, 95% CI (2.86-5)], male gender [OR 2.52, 95% CI (1.75-3.64)], history of pulmonary disease [OR 2.56, 95% CI (1.81-3.61)], coronary artery disease [OR 2.35, 95% CI (1.60-3.46)], and non-apical ballooning form [OR 1.47, 95% CI (1.02-2.13)] were associated with smoking status. Propensity score matching (PSM) 1:1 yielded 329 patients from each group. Smokers had a similar rate of in-hospital complications but longer in-hospital stays (10 vs. 9 days, p  = 0.01). During long-term follow-up, there were no differences in mortality rates between smokers and non-smokers (5.6% vs. 6.9% yearly in the overall, p  = 0.02, and 6.6%, vs. 7.2% yearly in the matched cohort, p  = 0.97)., Conclusions: Our findings suggest that smoking may influence the clinical presentation and course of TTS with longer in-hospital stays, but does not independently impact mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Núñez-Gil, Santoro, Vazirani, Novo, Blanco-Ponce, Arcari, Uribarri, Cacciotti, Guerra, Salamanca, Musumeci, Vedia, Mariano, Fernández-Cordón, Caldarola, Montisci, Brunetti, El-Battrawy, Abumayyaleh, Akin, Eitel and Stiermaier.)

Medical liability has become a challenge in every physician's modern practice with the consequent loss of the physician's autonomy and an increase in "defensive medicine". From this perspective, the role of Legal Medicine in assessing medical liability has become increasingly specific and a homogenization of the methods of ascertainment is increasingly necessary, since such a process can contribute to strengthening the guarantees in professional liability procedures. Focusing on malpractice claims in the field of cardiology, the complexity of the management of cardiac pathologies and the frequency of severe adverse events implies the importance of a multi-disciplinary approach, together with the application of a shared ascertainment methodology. In particular, it is essential for the forensic pathologist to collaborate with experts in cardio-pathology, cardiology and/or cardiac surgery in cases of alleged medical liability in the cardiologic field and to follow the guidelines which have been produced to assist the expert dealing with deaths reflecting cardiac disease, in order to prevent criticism of case analysis in medico-legal environments and to promote the standardization of the structure of the juridical-legislative medical malpractice lawsuits., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Although atherosclerosis is usually considered a disease of the large arteries, risk factors for atherosclerosis also trigger structural and functional abnormalities at a microvascular level. In cardiac disease, microvascular dysfunction is especially relevant in women, among whom the manifestation of ischemic disease due to impaired coronary microcirculation is more common than in men. This sex-specific clinical phenotype has important clinical implications and, given the higher pre-test probability of coronary microvascular dysfunction in females, different diagnostic modalities should be used in women compared to men. In this review, we summarize invasive and non-invasive diagnostic modalities to assess coronary microvascular function, ranging from catheter-based evaluation of endothelial function to Doppler echocardiography and positron emission tomography. Moreover, we discuss different clinical settings in which microvascular disease plays an important role, underlining the importance of choosing the right diagnostic modality depending on the sex of the patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Cannabis is the most consumed drug worldwide and number of users is increasing, particularly among youth. Moreover, cannabis potential therapeutic properties have renewed interest to make it available as a treatment for a variety of conditions. Albeit rarely, cannabis consumption has been associated with cardiovascular diseases such as arrhythmias, myocardial infarction (MI) and potentially sudden death., Case Presentation: A 24-year-old woman presented to the emergency department sent by her cardiologist because of a recent finding of a 16 seconds asystole on the implantable loop recorder (ILR) she implanted 7 months before for recurrent syncopes. She declared that she is a heavy cannabis user (at least 5 cannabis-cigarette per day, not mixed up with tobacco, for no less than 12 years) and all syncopes occurred shortly after cannabis consumption. After a collective discussion with the heart team, syncope unit, electrophysiologists and toxicologist, we decided to implant a dual chamber pacemaker with a rate response algorithm due to the high risk of trauma of the syncopal episodes. 24 months follow-up period was uneventful., Conclusions: Cannabis cardiovascular effects are not well known and, although rare, among these we find ischemic episodes, tachyarrhythmias, symptomatic sinus bradycardia, sinus arrest, ventricular asystole and possibly death. Because of cannabis growing consumption both for medical and recreational purpose, cardiovascular diseases associated with cannabis use may become more and more frequent. In the light of the poor literature, we believe that cannabis may produce opposite adverse effects depending on the duration of the habit. Acute administration increases sympathetic tone and reduces parasympathetic tone; conversely, with chronic intake an opposite effect is observed: repetitive dosing decreases sympathetic activity and increases parasympathetic activity. Clinicians should be aware of the increased risk of cardiovascular complications associated with cannabis use and should investigate its consumption especially in young patients presenting with cardiac dysrhythmias., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: The aims of our study were to investigate the sex differences in late gadolinium enhancement (LGE) using cardiovascular magnetic resonance (CMR) in a single-centre cohort of consecutive patients with acute myocarditis (AM)., Method: This retrospective study performed CMR scans in 135 consecutive patients with AM that met the Lake Louise criteria. On CMR, LV ventricular strain functions were performed on conventional cine SSFP sequences. Besides myocardial strain measurements, myocardial scar location, extension, and size were assigned and quantified by LGE imaging., Results: There was no difference in age (age 42.51 ± 19.64 years vs 40.92 ± 19.94 years; p = 0.74) and cardiovascular risk profile between women and men. Despite similar comorbidities, women were more like to present with dyspnea (p = 0.001). Women demonstrated higher prevalence of septal LGE (p = 0.004) and increased global circumferential strain parameters (p = 0.008) in comparison with men. In multivariate analysis, female sex remained an independent determinant of septal LGE (β coefficient = -0.520, p = 0.001)., Conclusion: This is the first study reporting sex differences in LGE localization in AM. Women have more septal LGE involvement independent of age, cardiovascular risk factors, and CMR parameters. These findings further emphasize the sex-based differences in cardiovascular diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Alexithymia has been found to be associated with several somatic illnesses, such as cardiovascular, indicating that it might be a risk factor for early death in the long-term course of post-myocardial infarction. From the cardiology perspective, the aim was to collect current evidence about the relationship between alexithymia and somatic illness., Methods: The literature was synthesized and summarized in a narrative format. The literature search was carried out in PubMed. Pertinent studies published in the last 50 years written in English were included and organized by three main topics ("The relation between alexithymia and somatic illness from the cardiology perspective"; "How do assess alexithymia?"; "Treating alexithymia") to be discussed., Results: High alexithymia is a dimensional trait that affects around 10% of the general population and up to 55% of people with essential hypertension. Also, the link between alexithymia and cardiovascular activity has been pointed out. There are several validated tools to assess alexithymia, as well as treatment options., Conclusion: Knowledge about the main features of alexithymia, as well as its assessment and treatment, can promote a multifactorial approach to the primary, secondary, and tertiary prevention of cardiac diseases., Competing Interests: Dr. Antonio Nardi is the Editorial Advisory Board member of the journal Clinical Practice & Epidemiology in Mental Health., (© 2023 Sancassiani et al.)

The study was designed to assess patient adherence to wearable cardioverter defibrillator as an indicator of device effectiveness. The patient training is not widely properly standardized. We enrolled 25 patients with a wearable cardioverter defibrillator to prevent sudden cardiac death between June 2020 and August 2022. Among them, 84% were male with a median age of 63.6 years. The indication was an ischemic (44%) and a non-ischemic (56%) disease. The patients were followed-up until the decision to upgrade to an implantable device was taken. We trained the patients according to our suggested protocol. The median wear time was 90 days, and the median daily wear time was 23.5 h, similar throughout sex, age, and indication groups. In total, 24% of the participants underwent cardioverter defibrillator implantation. Between the device-implanted and non-implanted groups, left ventricular ejection fraction and left ventricular indexed end-diastolic volume were significantly different (EF 35.8 ± 12 vs. 46.4 ± 8.5%, p = 0.028, iEDV 108 ± 52 vs. 70.7 ± 21.1 mL/m 2 , p = 0.024). We did not find any differences in cardiac magnetic resonance data, even though all patients who underwent device implantation had late gadolinium enhancement spots. Our results support standardized patient training to obtain great patient adherence to the instructions to the wearable device and therefore its effectiveness.

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.

Alexithymia literally meaning 'no words for emotions' is a term used in mental health settings to describe people who have difficulties in identifying and verbalizing their emotional states. There is evidence in the literature that this personality trait may influence negatively the illness behavior when an acute coronary event occurs. In fact, people with high alexithymia are more likely to experience wrong appraisal and interpretation of symptoms, and because of their difficulty in describing feelings to others, they can be poor in reporting symptoms at the first consultation with a physician. This behavioral pattern (alexithymic) may put patients with acute myocardial infarction at higher risk for delayed medical care. Here, we aim to present an overview of alexithymia from the perspective of the clinical cardiologist, with a focus on the definition, clinical recognition, and potential impact on cardiovascular health., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: Catecholamine-induced Takotsubo Syndrome (cat-TS) is a type of secondary Takotsubo syndrome, characterized by rapid onset of symptoms, high rate of complications during the acute phase, good short-term prognosis, and frequent apical sparing at echocardiogram. We present two clinical cases of cat-TS treated in our department., Case Summary: Case one: 78-year-old man, admitted to Ear Nose and Throat Unit for surgical removal of oral squamous cellular carcinoma. During surgery, the occurrence of hypotensive episode was treated with catecholamines. After surgery, the occurrence of atrial fibrillation was followed by evidence of phasic increase of troponin levels and akinesia of midventricular segments. Angiography showed the absence of significant coronary stenoses, and during hospital stay, we observed rapid recovery of wall motion abnormalities. Case two: 64-year-old woman, admitted for hysteropexy surgery, during which cardiac arrest occurred, treated with epinephrine i.v.1 mg and DC shock. Two hours after resuscitation, the patient developed pulmonary oedema, troponin levels increased progressively, and the echocardiogram demonstrated hypokinesia in all midventricular segments with apical sparing. Afterwards, an urgent angiography highlighted normal coronary anatomy. Cardiac magnetic resonance imaging (MRI) revealed oedema corresponding to hypokinetic areas. On the seventh day, echocardiogram showed a complete remission of wall motion abnormalities., Discussion: These cases warn the physicians about the importance of routinely screening myocardial impairment through clinical assessment, electrocardiogram (ECG) monitoring, and serial cardiac troponin testing after catecholamine i.v. bolus administration. In case of alterations of these exams, performing a prompt echocardiogram allows early detection of cat-TS, to provide immediate suitable medical support and avoid complications., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Evaluation of coronary flow velocity reserve (CFVR) is the physiological approach to assess the severity of coronary stenosis and microvascular dysfunction. Impaired CFVR occurs frequently in women with suspected or known coronary artery disease. The aim of this study was to assess the role of CFVR to predict long-term cardiovascular event rate in women with unstable angina (UA) without obstructive coronary artery stenosis., Methods: CFVR in left anterior descending coronary artery was assessed by adenosine transthoracic echocardiograhy in 161 women admitted at our Department with UA and without obstructive coronary artery disease., Results: During a mean FU of 32.5 ± 19.6 months, 53 cardiac events occurred: 6 nonfatal acute myocardial infarction, 22 UA, 7 coronary revascularization by percutaneous transluminal coronary angioplasty, 1 coronary bypass surgery, 3 ischemic stroke, and 8 episodes of congestive heart failure with preserved ejection fraction and 6 cardiac deaths. Using a ROC curve analysis, CFVR 2.14 was the best predictor of cardiac events and was considered as abnormal CFVR. Abnormal CFVR was associated with lower cardiac event-free survival (30 vs 80%, p < 0.0001). During FU, 70% of women with reduced CFVR had cardiac events whereas only 20% with normal CFVR (p = 0.0001). At multivariate Cox analysis, smoke habitus (p = 0.003), metabolic syndrome (p = 0.01), and CFVR (p < 0.0001) were significantly associated with cardiac events at FU., Conclusion: Noninvasive CFVR provides an independent predictor of cardiovascular prognosis information in women with UA without obstructive coronary artery disease whereas, impaired CFVR seems to be associated with higher CV events at FU., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

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.

Age is a non-modifiable cardiovascular risk factor, which leads to development and progression of chronic conditions, such as coronary artery disease, by promoting atherosclerosis. Aging is responsible for morphological structure changes of the coronary arteries and specific atherosclerotic plaque features, which can be studied with non-invasive coronary imaging techniques, particularly coronary CT angiography. The aim of this review is to evaluate current knowledge on this technique applied to the elderly population, and to describe CAD manifestation and plaque features of coronary atherosclerosis in this particular set of patients. We also discuss the clinical implication of frailty assessment and customization of diagnostic strategies in order to shift the approach from disease-centered to patient-centered care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Takotsubo cardiomyopathy (TTC) is a transient but severe acute myocardial dysfunction with a wide range of outcomes from favorable to life-threatening. The current risk stratification scores of TTC patients do not include cardiac magnetic resonance (CMR) parameters. To date, it is still unknown whether and how clinical, trans-thoracic echocardiography (TTE), and CMR data can be integrated to improve risk stratification., Methods: EVOLUTION (Exploring the eVolution in prognOstic capabiLity of mUlti-sequence cardiac magneTIc resOnance in patieNts affected by Takotsubo cardiomyopathy) is a multicenter, international registry of TTC patients who will undergo a clinical, TTE, and CMR evaluation. Clinical data including demographics, risk factors, comorbidities, laboratory values, ECG, and results from TTE and CMR analysis will be collected, and each patient will be followed-up for in-hospital and long-term outcomes. Clinical outcome measures during hospitalization will include cardiovascular death, pulmonary edema, arrhythmias, stroke, or transient ischemic attack.Clinical long-term outcome measures will include cardiovascular death, pulmonary edema, heart failure, arrhythmias, sudden cardiac death, and major adverse cardiac and cerebrovascular events defined as a composite endpoint of death from any cause, myocardial infarction, recurrence of TTC, transient ischemic attack, and stroke. We will develop a comprehensive clinical and imaging score that predicts TTC outcomes and test the value of machine learning models, incorporating clinical and imaging parameters to predict prognosis., Conclusions: The main goal of the study is to develop a comprehensive clinical and imaging score, that includes TTE and CMR data, in a large cohort of TTC patients for risk stratification and outcome prediction as a basis for possible changes in patient management., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) is a key diagnostic tool in the differential diagnosis between non-ischemic cause of cardiac chest pain. Some patients are not eligible for a gadolinium contrast-enhanced CMR; in this scenario, the diagnosis remains challenging without invasive examination. Our purpose was to derive a machine learning model integrating some non-contrast CMR parameters and demographic factors to identify Takotsubo cardiomyopathy (TTC) in subjects with cardiac chest pain., Material and Methods: Three groups of patients were retrospectively studied: TTC, acute myocarditis, and healthy controls. Global and regional left ventricular longitudinal, circumferential, and radial strain (RS) analysis included were assessed. Reservoir, conduit, and booster bi-atrial functions were evaluated by tissue-tracking. Parametric mapping values were also assessed in all the patients. Five different tree-based ensemble learning algorithms were tested concerning their ability in recognizing TTC in a fully cross-validated framework., Results: The CMR-based machine learning (ML) ensemble model, by using the Extremely Randomized Trees algorithm with Elastic Net feature selection, showed a sensitivity of 92% (95% CI 78-100), specificity of 86% (95% CI 80-92) and area under the ROC of 0.94 (95% CI 0.90-0.99) in diagnosing TTC. Among non-contrast CMR parameters, the Shapley additive explanations analysis revealed that left atrial (LA) strain and strain rate were the top imaging markers in identifying TTC patients., Conclusions: Our study demonstrated that using a tree-based ensemble learning algorithm on non-contrast CMR parameters and demographic factors enables the identification of subjects with TTC with good diagnostic accuracy., Translational Outlook: Our results suggest that non-contrast CMR features can be implemented in a ML model to accurately identify TTC subjects. This model could be a valuable tool for aiding in the diagnosis of subjects with a contraindication to the contrast media. Furthermore, the left atrial conduit strain and strain rate were imaging markers that had a strong impact on TTC identification. Further prospective and longitudinal studies are needed to validate these findings and assess predictive performance in different cohorts, such as those with different ethnicities, and social backgrounds and undergoing different treatments., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: Takotsubo syndrome (TTS) is an acute and reversible left ventricular dysfunction and can be complicated by cardiogenic shock (CS). However, few data are available on optimal care in TTS complicated by CS. Aim of this study was to evaluate short- and long-term impact of intra-aortic balloon pumping (IABP) on mortality in this setting., Methods and Results: In a multi-centre, international registry on TTS, 2248 consecutive patients were enrolled from 38 centres from Germany, Italy, and Spain. Of the 2248 patients, 212 (9.4%) experienced CS. Patients with CS had a higher prevalence of diabetes (27% vs. 19%), male sex (25% vs. 10%), and right ventricular involvement (10% vs. 5%) ( P < 0.01 in all cases). Forty-three patients with CS (20% of 212) received IABP within 8 h (interquartile range 4-18) after admission. No differences in terms of age, gender, cardiovascular risk factors, and admission left ventricular ejection fraction were found among patients with and without IABP. There were no significant differences in terms of 30-day mortality (16% vs. 17%, P = 0.98), length of hospitalization (18.9 vs. 16.7 days, P = 0.51), and need of invasive ventilation (35% vs. 41%, P = 0.60) among two groups: 30-day survival was not significantly different even after propensity score adjustment (log-rank P = 0.73). At 42-month follow-up, overall mortality in patients with CS and TTS was 35%, not significantly different between patients receiving IABP and not (37% vs. 35%, P = 0.72)., Conclusions: In a large multi-centre observational registry, the use of IABP was not associated with lower mortality rates at short- and long-term follow-up in patients with TTS and CS., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Coronary flow velocity reserve (CFVR) is defined as the ratio between coronary flow velocity during maximal hyperemia and coronary flow at rest. Gold-standard techniques to measure CFVR are either invasive or require radiation and are therefore inappropriate for large-scale adoption. More than 30 years ago, echocardiography was demonstrated to be a reliable tool to assess CFVR, and its field of application rapidly expanded. Although initially validated to assess the hemodynamic relevance of a coronary stenosis, CFVR by echocardiography was later used to investigate coronary microcirculation. Microvascular dysfunction was detected in many different conditions, ranging from organ transplantation to inflammatory disorders and from metabolic diseases to cardiomyopathies. Moreover, it has been proven that CFVR by echocardiography not only detects coronary microvascular involvement but is also an effective prognostic factor that allows a precise risk stratification of the patients. In this review, we will summarize the many applications of CFVR by echocardiography, focusing on the coronary involvement of systemic diseases., Competing Interests: The authors declare no conflict of interest.

Immune checkpoint inhibitor (ICI)-induced cardiotoxicity is a rare immune-related adverse event (irAE) characterized by a high mortality rate. From a pathological point of view, this condition can result from a series of causes, including binding of ICIs to target molecules on nonlymphocytic cells, cross-reaction of T lymphocytes against tumor antigens with off-target tissues, generation of autoantibodies and production of proinflammatory cytokines. The diagnosis of ICI-induced cardiotoxicity can be challenging, and cardiac magnetic resonance (CMR) represents the diagnostic tool of choice in clinically stable patients with suspected myocarditis. CMR is gaining a central role in diagnosis and monitoring of cardiovascular damage in cancer patients, and it is entering international cardiology and oncology guidelines. In this narrative review, we summarized the clinical aspects of ICI-associated myocarditis, highlighting its radiological aspects and proposing a novel algorithm for the use of CMR., (© 2022 UICC.)

Takotsubo syndrome (TTS) is usually caused by physical or emotional negative stressors. Sometimes positive emotions trigger a rare form of Takotsubo syndrome, called the "happy heart" syndrome. We discuss the management of a 52-year-old female with happy heart syndrome, the differences between these stress cardiomyopathies and the relationship with hyperthyroidism., Learning Points: The happy heart syndrome is less common than other stress cardiomyopathies but emergency doctors, cardiologists and all specialists in internal medicine should take into account this cardiomyopathy, which occurs in patients with previous positive emotions. It is triggered by opposite stressors to Takotsubo syndrome and sometimes it may be misdiagnosed. Beyond triggers it has some different clinical features, and the management is similar. It is a rare disease, and is therefore underdiagnosed.Everybody experiences positive emotions in life but only a small percentage develop stress cardiomyopathy. A susceptibility is needed to trigger these cardiomyopathies such as hyperthyroidism, which has to be promptly treated with an endocrinologist's help.In clinical practice it is common to diagnose stress cardiomyopathies without following up the patients. We need to follow up these patients especially looking for concomitant conditions such as hyperthyroidism or hypersympathetic activity, which could present during follow-up., Competing Interests: Conflicts of Interests: The authors declare there are no competing interests., (© EFIM 2022.)

Background: Preliminary in vitro and in vivo studies have supported the efficacy of the peroxisome proliferator-activated receptor-γ (PPARγ) modulator N-acetyl-GED-0507-34-LEVO (NAC-GED) for the treatment of acne-inducing sebocyte differentiation, improving sebum composition and controlling the inflammatory process., Objectives: To evaluate the efficacy and safety of NAC-GED (5% and 2%) in patients with moderate-to-severe facial acne vulgaris., Methods: This double-blind phase II randomized controlled clinical trial was conducted at 36 sites in Germany, Italy and Poland. Patients aged 12-30 years with facial acne, an Investigator Global Assessment (IGA) score of 3-4, and an inflammatory and noninflammatory lesion count of 20-100 were randomized to topical application of the study drug (2% or 5%) or placebo (vehicle), once daily for 12 weeks. The co-primary efficacy endpoints were percentage change from baseline in total lesion count (TLC) and IGA success at week 12; the safety endpoints were adverse events (AEs) and serious AEs. This study was registered with EudraCT (2018-003307-19)., Results: Between Q1 in 2019 and Q1 in 2020 450 patients [n = 418 (92·9%) IGA 3; n = 32 (7·1%) IGA 4] were randomly assigned to NAC-GED 5% (n = 150), NAC-GED 2% (n = 150) or vehicle (n = 150). The percentage change in TLC reduction was statistically significantly higher in both the NAC-GED 5% [-57·1%, 95% confidence interval (CI) -60·8 to -53·4; P < 0·001] and NAC-GED 2% (-44·7%, 95% CI -49·1 to -40·1; P < 0·001) groups compared with vehicle (-33·9%, 95% CI -37·6 to -30·2). A higher proportion of patients treated with NAC-GED 5% experienced IGA success (45%, 95% CI 38-53) vs. the vehicle group (24%, 95% CI 18-31; P < 0·001). The IGA success rate was 33% in the NAC-GED 2% group (P = not significant vs. vehicle). The percentage of patients who had one or more AEs was 19%, 16% and 19% in the NAC-GED 5%, NAC-GED 2% and vehicle groups, respectively., Conclusions: The topical application of NAC-GED 5% reduced TLC, increased the IGA success rate and was safe for use in patients with acne vulgaris. Thus, NAC-GED, a new PPARγ modulator, showed an effective clinical response. What is already known about this topic? Acne vulgaris, one of the most common dermatological diseases, affects more than 85% of adolescents. There is a medical need for innovative and safe treatment of acne vulgaris. The peroxisome proliferator-activated receptor-γ (PPARγ) is involved in lipid metabolism and specifically in cell differentiation, sebum production and the inflammatory reaction. What does this study add? N-acetyl-GED-0507-34-LEVO (NAC-GED 5%), a PPARγ modulator, significantly improves acne manifestations in patients with moderate-to-severe acne and is safe and well tolerated. The results suggest that the PPARγ receptor is a novel therapeutic target for acne. The results provide a basis for a large phase III trial to assess the effectiveness and safety profile of NAC-GED in combating a disease that afflicts 80-90% of adolescents., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Physical exercise has been shown to improve dysmetabolism in older adults, reducing cardiovascular risk, while its role in preventing dysmetabolism is less known. Moreover, most of the trials use exercise programs that are difficult to put into daily practice. The purpose of this Randomized Controlled Trial (RCT) was to evaluate the effectiveness of a 3-month moderate exercise program in improving or preventing dysmetabolism in 120 older adults, randomly selected for the exercise program (experimental group) or cultural activities (control group). None of the subjects were following a hypocaloric diet, and all of them reported healthy eating habits. Anthropometric (Body Mass Index (BMI) and Waist Circumference (WC)) and metabolic variables (fasting plasma glucose (FPG), High-Density Lipoprotein Cholesterol (HDL-C), and triglycerides (TG)) were assessed at baseline (T0) and at the end of the trial (T1). Dysmetabolism was defined by the presence of an increased WC plus at least two metabolic alterations. At T0, the two groups did not differ by sex, age, education, BMI, WC, FPG, HDL-C levels, and prevalence of dysmetabolism. The mean BMI value indicated overweight, and WC values were higher than the cut-off. At T1, a slight reduction in the number of people with dysmetabolism was found only in the experimental group. However, none of the individuals without dysmetabolism at T0 in the experimental group developed it at T1, while 11.4% developed it in the control group ( p = 0.032). This study highlights that a moderate exercise program, accessible in daily practice, can prevent dysmetabolism in older adults, even while being overweight, while if dysmetabolism is already present, more prolonged combined nutritional and exercise interventions will be needed.

Background: The association with a preceding stressor is a characteristic feature of takotsubo syndrome (TTS). Negative emotions before TTS are common and led to the popular term "broken heart syndrome." In contrast, pleasant triggers ("happy heart syndrome") are rare and are scarcely investigated., Objectives: The authors analyzed the frequency, clinical characteristics, and prognostic implications of positive emotional stressors in the multicenter GEIST (GErman-Italian-Spanish Takotsubo) Registry., Methods: Patients enrolled in the registry were categorized according to their stressors. This analysis compared patients with pleasant emotional events with patients with negative emotional events., Results: Of 2,482 patients in the registry, 910 patients (36.7%) exhibited an emotional trigger consisting of 873 "broken hearts" (95.9%) and 37 "happy hearts" (4.1%). Consequently, the prevalence of pleasant emotional triggers was 1.5% of all TTS cases. Compared with patients with TTS with negative preceding events, patients with happy heart syndrome were more frequently male (18.9% vs 5.0%; P < 0.01) and had a higher prevalence of atypical ballooning patterns (27.0% vs 12.5%; P = 0.01), particularly midventricular ballooning. In-hospital complications, including death, pulmonary edema, cardiogenic shock, or stroke (8.1% vs 12.3%; P = 0.45), and long-term mortality rates (2.7% vs 8.8%; P = 0.20) were similar in "happy hearts" and "broken hearts.", Conclusions: Happy heart syndrome is a rare type of TTS characterized by a higher prevalence of male patients and atypical, nonapical ballooning compared with patients with negative emotional stressors. Despite similar short- and long-term outcomes in our study, additional data are needed to explore whether numerically lower event rates in "happy hearts" would be statistically significant in a larger sample size. (GErman-Italian-Spanish Takotsubo Registry [GEIST Registry]; NCT04361994)., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)