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Objectives: Cardiac telerehabilitation (TR) for coronary artery disease (CAD) is a feasible alternative to the center-based rehabilitation delivery model. However, the features of exercise-based cardiac TR are still heterogeneous among studies, making it difficult to disentangle the preferable reference strategies to be recommended for the adoption of this new delivery of care. In addition, little is known about the effectiveness of different models, such as the hybrid model (CRh) including both center-based and home-based telerehabilitation approaches, and the solely home-based telerehabilitation (CTR). Methods: We conducted a systematic review of randomized controlled trials (RCTs) that included TR intervention in patients with CAD to profile the features of the telerehabilitation approach for CAD. We also conducted a meta-analysis to separately assess the effectiveness of CTR and CRh on medical benefit outcome measures compared to conventional intervention (CI). Results: Out of 17.692 studies, 28 RCTs involving 2.662 CAD patients were included in the review. The studies presented an equal proportion of the CTR and CRh models. The interventions were mainly multidimensional, with a frequency of 1 month to 6 months, with each session ranging between 20 to 70 min. In CRh, the intervention was mainly consecutive to center-based rehabilitation. All studies adopted asynchronous communication in TR, mainly providing monitoring/assessment, decisions, and offline feedback. Few studies reported mortality, and none reported data about re-hospitalization or morbidity. Adherence to the CTR and CRh interventions was high (over 80%). The meta-analyses showed the superior effect of CTR compared to CI in exercise capacity. An overall noninferiority effect of both CTR and CRh compared to CI was found with factors including risk control and participation. Conclusions: The results of the review and meta-analyses indicated that CTR and CRh are equally effective, safe, convenient, and valid alternatives to cardiac conventional interventions. The evidence suggests that telerehabilitation may represent a valid alternative to overcome cardiac rehabilitation barriers.

This systematic review investigates the diagnostic and prognostic utility of coronary flow reserve (CFR) assessment through echocardiography in patients with left bundle branch block (LBBB), a condition known to complicate the clinical evaluation of coronary artery disease (CAD). The literature search was performed on PubMed, EMBASE, Web of Science, Scopus, and Google Scholar, was guided by PRISMA standards up to March 2024, and yielded six observational studies that met inclusion criteria. These studies involved a diverse population of patients with LBBB, employing echocardiographic protocols to clarify the impact of LBBB on coronary flow dynamics. The findings emphasize the importance of CFR in stratifying cardiovascular risk and guiding clinical decision-making in patients with LBBB. Pooled results reveal that patients with LBBB and significant left anterior descending (LAD) artery stenosis exhibited a marked decrease in stress-peak diastolic velocity (MD = -19.03 [-23.58; -14.48] cm/s; p < .0001) and CFR (MD = -.60 [-.71; -.50]; p < .0001), compared to those without significant LAD lesions, suggesting the efficacy of stress echocardiography CFR assessment in the identification of clinically significant CAD among the LBBB population. This review highlights the clinical relevance of echocardiography CFR assessment as a noninvasive tool for evaluating CAD and stratifying risk in the presence of LBBB and underscores the need for standardized protocols in CFR measurement., (© 2024 Wiley Periodicals LLC.)

Purpose : Myocarditis is frequently a sporadic disease, but may also occur in the context of genetic disorders which may increase susceptibility to cardiac inflammation. Cardiac involvement in Wolfram syndrome type 1 (WS1) has been scarcely characterized. To our knowledge, no cases of virus-negative myocarditis have been reported in the WS1 pediatric population. Methods : We report the description of a pediatric case of acute myocarditis in the context of WS1, followed by a literature review of cardiovascular involvement associated with wolframin variants, and discuss potential pathophysiological mechanisms and therapeutic options. Results : A young patient with WS1, treated with insulin and liraglutide, was admitted for acute chest pain. Cardiac magnetic resonance and endomyocardial biopsy were performed to confirm the clinical suspicion of myocarditis. While congenital heart diseases and arrhythmias have been described previously in patients with WS1, this is the first description of virus-negative myocarditis. Conclusions : Myocarditis may represent a possible manifestation of cardiovascular involvement in WS1. Cardiovascular screening may be considered in patients with WS1.

This review aims to delineate the potential impact of static meditation practice on cholesterol and triglyceride levels. PubMed, EMBASE, Web of Science, Cochrane Library, and Google Scholar were systematically screened up until December 2023 to identify pertinent studies. After searching the scientific literature, 16 clinical studies (11 trials and 5 observational experiments) met the criteria for inclusion, involving a total of 1147 participants. In general, Ayurvedic-based meditation techniques were predominantly associated with lower total cholesterol levels, mindfulness-based techniques demonstrated benefits in both total cholesterol and triglyceride levels, and Eastern meditation techniques with spiritual origins were primarily linked to improved serum concentrations of HDL cholesterol. Study participants mostly engaged in meditation on a daily basis, often practicing it once or even twice a day, spanning a duration ranging from a few weeks to several months. The meta-analysis shows an association between meditation practice in healthy or sub-healthy adults and reduced cholesterol levels, with an average decrease of approximately -14 mg/dL (MD = -13.91 [-23.35; -4.47] mg/dL; p = 0.02), alongside favorable and even more pronounced impacts on triglyceride levels (MD = -32.56 [-48.44; -16.68] mg/dL; p < 0.01). In summary, regular engagement in static meditation practices can be associated with lower triglyceride and, to a lesser extent, cholesterol levels. Further studies on the topic are recommended to better investigate the relationship between meditation practice and physiological parameters.

Peripartum Cardiomyopathy (PPCM) is a polymorphic myocardial disease occurring late during pregnancy or early after delivery. While reduced systolic function and heart failure (HF) symptoms have been widely described, there is still a lack of reports about the arrhythmic manifestations of the disease. Most importantly, a broad range of unidentified pre-existing conditions, which may be missed by general practitioners and gynecologists, must be considered in differential diagnosis. The issue is relevant since some arrhythmias are associated to sudden cardiac death occurring in young patients, and the overall risk does not cease during the early postpartum period. This is why multimodality diagnostic workup and multidisciplinary management are highly suggested for these patients. We reported a series of 16 patients diagnosed with PPCM following arrhythmic clinical presentation. Both inpatients and outpatients were identified retrospectively. We performed several tests to identify the arrhythmic phenomena, inflammation and fibrosis presence. Cardiomyopathies phenotypes were reclassified in compliance with the updated ESC guidelines recommendations. Arrhythmias were documented in all the patients during the first cardiological assessment. PVC were the most common recorder arrhythmias, followed by VF, NSVT, AF, CSD., 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., (© 2024 Peretto, Micaglio, Ciconte, Maia, Luzzi, Cariello, Bonfanti, Lazzeroni, Anastasia, Cavoretto, Chieffo, Della Bella and Pappone.)

Aims: Coronary artery ectasia (CAE) has been linked to the occurrence of adverse events in patients with ischemia/angina and no obstructive coronary arteries (INOCA/ANOCA), while the relationship between CAE and myocardial infarction with nonobstructive coronary arteries (MINOCA) has been poorly investigated. In our study we aimed at assessing differences in clinical, angiographic and prognostic features among patients with CAE and MINOCA vs. INOCA/ANOCA presentation., Methods: Patients with angiographic evidence of CAE were enrolled at the University Hospital of Parma and divided into MINOCA vs. INOCA/ANOCA presentation. Clinical and quantitative angiographic information was recorded and the incidence of major adverse cardiovascular events (MACE) was assessed at follow-up., Results: We enrolled a total of 97 patients: 49 (50.5%) with MINOCA and 48 (49.5%) with INOCA/ANOCA presentation. The presentation with MINOCA was associated with a higher frequency of inflammatory diseases ( P  = 0.041), multivessel CAE ( P  = 0.030) and thrombolysis in myocardial infarction (TIMI) flow < 3 ( P  = 0.013). At a median follow-up of 38 months, patients with MINOCA had a significantly higher incidence of MACE compared with those with INOCA/ANOCA [8 (16.3%) vs. 2 (4.2%), P  = 0.045], mainly driven by a higher rate of nonfatal MI [5 (10.2%) vs. 0 (0.0%), P  = 0.023]. At multivariate Cox regression analysis, the presentation with MINOCA ( P  = 0.039) and the presence of TIMI flow <3 ( P  = 0.037) were independent predictors of MACE at follow-up., Conclusion: Among a cohort of patients with CAE and nonobstructive coronary artery disease, the presentation with MINOCA predicted a worse outcome., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Aim: To compare the efficacy of polymer-free drug-eluting stents (PF-DES) versus other stents in diabetic patients with coronary artery disease undergoing percutaneous coronary interventions. Materials & methods: A systematic review and meta-analysis were performed to identify pertinent randomized controlled trials. The primary end point was the occurrence of target lesion failure. Results: Eight randomized controlled trials were included for a total of 4854 subjects. The PF-DES group experienced a trend in favor of a lower rate of target lesion failure (Incidence rate ratio = 0.91; p  = 0.11) and a significantly lower rate of cardiac mortality, as compared with the control group (Incidence rate ratio = 0.82; p  = 0.04). However, statistical significance was lost if bare-metal stent patients were excluded and a trend in favor of the PF-DES strategy was reported only for cardiac mortality. Conclusion: PF-DES could be a valuable strategy in diabetic patients with coronary artery disease undergoing percutaneous coronary interventions.

Aims: Globally, nearly 20% of cardiovascular disease deaths were attributable to air pollution. Out-of-hospital cardiac arrest (OHCA) represents a major public health problem; therefore, the identification of novel OHCA triggers is of crucial relevance. The aim of the study was to evaluate the association between air pollution (short-, mid-, and long-term exposures) and OHCA risk, during a 7-year period in a highly polluted urban area in northern Italy, with a high density of automated external defibrillators (AEDs)., Methods and Results: Out-of-hospital cardiac arrests were prospectively collected from the 'Progetto Vita Database' between 1 January 2010 and 31 December 2017; day-by-day air pollution levels were extracted from the Environmental Protection Agency stations. Electrocardiograms of OHCA interventions were collected from the AED data cards. Day-by-day particulate matter (PM) 2.5 and 10, ozone (O3), carbon monoxide (CO), and nitrogen dioxide (NO2) levels were measured. A total of 880 OHCAs occurred in 748 days. A significant increase in OHCA risk with a progressive increase in PM2.5, PM10, CO, and NO2 levels was found. After adjustment for temperature and seasons, a 9% and 12% increase in OHCA risk for each 10 μg/m3 increase in PM10 (P < 0.0001) and PM2.5 (P < 0.0001) levels was found. Air pollutant levels were associated with both asystole and shockable rhythm risk, while no correlation was found with pulseless electrical activity., Conclusion: Short- and mid-term exposures to PM2.5 and PM10 are independently associated with the risk of OHCA due to asystole or shockable rhythm., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The authors present a clinical report focused on the overlap between myocarditis and genetic cardiomyopathies of the dilated and arrhythmogenic spectrum. Our cohort was composed of 25 patients undergoing extensive baseline characterization and prospective reassessment by a dedicated multidisciplinary disease unit during a median follow-up of 69 months. We showed that the use of multimodal imaging allowed both discrimination of specific genotypes and identification of myocardial inflammation proven using endomyocardial biopsy. In addition, we showed that the use of immunomodulatory therapy was beneficial for most patients., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Happiness is receiving more and more interest both as a determinant of health and a measure of outcome in biomedical and psychological sciences. The main objective of this study was to assess how the levels of happiness vary in a large sample of Italian adults and to identify the socio-demographic conditions which impair happiness domains the most. The participants of this survey consisted of 1695 Italian adults (85.9% women; 14.1% men) who completed the Measure of Happiness (MH) questionnaire online. In this study, the differences between groups in total and single domain (life perspective, psychophysical status, socio-relational sphere, relational private sphere, and financial status) happiness levels were examined through a propensity score matching analysis with respect to socio-demographic conditions, including gender, age, annual income, relationship status, having children, and education level. The results show that low income has a negative impact on happiness levels, whereas being in a relationship has a positive effect. Having children appears to have a negative impact on male happiness. Males appear to be happier than females, especially with regard to the psychophysics status. This evidence emphasizes the urgency for Italian policymakers to take actions on removing obstacles to people's happiness, especially with regard to financial distress, parenthood, and gender gaps.

Sudden cardiac death represents the leading cause of death worldwide; although the majority of sudden deaths occur in an elderly population with coronary artery disease, some occur in young and otherwise healthy individuals, as is the case of cardiomyopathies. The aim of the present review is to provide a stepwise hierarchical approach for the global sudden death risk estimation in primary cardiomyopathies. Each individual risk factor is analyzed for its contribution to the overall risk of sudden death for each specific cardiomyopathy as well as across all primary myocardial diseases. This stepwise hierarchical and personalized approach starts from the clinical evaluation, subsequently passes through the role of electrocardiographic monitoring and multimodality imaging, and finally concludes with genetic evaluation and electro-anatomical mapping. In fact, the sudden cardiac death risk assessment in cardiomyopathies depends on a multiparametric approach. Moreover, current indications for ventricular arrhythmia ablation and defibrillator implantation are discussed.

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.

Over recent years, preclinical and clinical evidence has implicated myocardial inflammation (M-Infl) in the pathophysiology and phenotypes of traditionally genetic cardiomyopathies. M-Infl resembling myocarditis on imaging and histology occurs frequently as a clinical manifestation of classically genetic cardiac diseases, including dilated and arrhythmogenic cardiomyopathy. The emerging role of M-Infl in disease pathophysiology is leading to the identification of druggable targets for molecular treatment of the inflammatory process and a new paradigm in the field of cardiomyopathies. Cardiomyopathies constitute a leading cause of heart failure and arrhythmic sudden death in the young population. The aim of this review is to present, from bedside to bench, the current state of the art about the genetic basis of M-Infl in nonischemic cardiomyopathies of the dilated and arrhythmogenic spectrum in order to prompt future research towards the identification of novel mechanisms and treatment targets, with the ultimate goal of lowering disease morbidity and mortality.

This systematic review explores the influence of silence on the autonomic nervous system. The Polyvagal Theory has been used as a reference model to describe the autonomic nervous system by explaining its role in emotional regulation, social engagement, and adaptive physiological responses. PubMed, Scopus, PsycInfo, EMBASE, and Google Scholar were systematically searched up until July 2023 for relevant studies. The literature search yielded 511 results, and 37 studies were eventually included in this review. Silence affects the autonomic nervous system differently based on whether it is inner or outer silence. Inner silence enhances activity of the ventral vagus, favoring social engagement, and reducing sympathetic nervous system activity and physiological stress. Outer silence, conversely, can induce a heightened state of alertness, potentially triggering vagal brake removal and sympathetic nervous system activation, though with training, it can foster inner silence, preventing such activation. The autonomic nervous system response to silence can also be influenced by other factors such as context, familiarity with silence, presence and quality of outer noise, and empathy., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aging is associated with an increasing burden of morbidity, especially for cardiovascular diseases (CVDs). General cardiovascular risk factors, ischemic heart diseases, heart failure, arrhythmias, and cardiomyopathies present a significant prevalence in older people, and are characterized by peculiar clinical manifestations that have distinct features compared with the same conditions in a younger population. Remarkably, the aging heart phenotype in both healthy individuals and patients with CVD reflects modifications at the cellular level. An improvement in the knowledge of the physiological and pathological molecular mechanisms underlying cardiac aging could improve clinical management of older patients and offer new therapeutic targets.

Objective: Coronary microvascular dysfunction (CMD) is a key pathophysiological feature of hypertrophic cardiomyopathy (HCM), contributing to myocardial ischemia and representing a critical determinant of patients' adverse outcome. The molecular mechanisms underlying the morphological and functional changes of CMD are still unknown. Aim of this study was to obtain insights on the molecular pathways associated with microvessel remodeling in HCM., Methods: Interventricular septum myectomies from patients with obstructive HCM (n = 20) and donors' hearts (CTRL, discarded for technical reasons, n = 7) were collected. Remodeled intramyocardial arterioles and cardiomyocytes were microdissected by laser capture and next-generation sequencing was used to delineate the transcriptome profile., Results: We identified 720 exclusive differentially expressed genes (DEGs) in cardiomyocytes and 1315 exclusive DEGs in remodeled arterioles of HCM. Performing gene ontology and pathway enrichment analyses, we identified selectively altered pathways between remodeled arterioles and cardiomyocytes in HCM patients and controls., Conclusions: We demonstrate the existence of distinctive pathways between remodeled arterioles and cardiomyocytes in HCM patients and controls at the transcriptome level., (© 2022 The Authors. Microcirculation published by John Wiley & Sons Ltd.)

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. The molecular mechanisms determining HCM phenotypes are incompletely understood. Myocardial biopsies were obtained from a group of patients with obstructive HCM (n = 23) selected for surgical myectomy and from 9 unused donor hearts (controls). A subset of tissue-abundant myectomy samples from HCM (n = 10) and controls (n = 6) was submitted to laser-capture microdissection to isolate cardiomyocytes. We investigated the relationship among clinical phenotype, cardiac myosin proteins (MyHC6, MyHC7, and MyHC7b) measured by optimized label-free mass spectrometry, the relative genes ( MYH7 , MYH7B and MYLC2 ), and the MyomiR network (myosin-encoded microRNA ( miRs ) and long-noncoding RNAs ( Mhrt )) measured using RNA sequencing and RT-qPCR. MyHC6 was lower in HCM vs. controls, whilst MyHC7, MyHC7b, and MyLC2 were comparable. MYH7, MYH7B , and MYLC2 were higher in HCM whilst MYH6 , miR-208a, miR-208b, miR-499 were comparable in HCM and controls. These results are compatible with defective transcription by active genes in HCM. Mhrt and two miR-499 -target genes, SOX6 and PTBP3 , were upregulated in HCM. The presence of HCM-associated mutations correlated with PTBP3 in myectomies and with SOX6 in cardiomyocytes. Additionally, iPSC-derived cardiomyocytes, transiently transfected with either miR-208a or miR-499 , demonstrated a time-dependent relationship between MyomiRs and myosin genes. The transfection end-stage pattern was at least in part similar to findings in HCM myectomies. These data support uncoupling between myosin protein/genes and a modulatory role for the myosin/MyomiR network in the HCM myocardium, possibly contributing to phenotypic diversity and providing putative therapeutic targets., Competing Interests: The authors declare no conflict of interest.

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.

Objective: Psychopathology (and depression in particular) is a cardiovascular risk factor independent from any co-occurring pathology. This link is traced back to the mind-heart-body connection, whose underlying mechanisms are still not completely known. To study psychopathology in relation to the heart, it is necessary to observe the autonomic nervous system, which mediates among the parts of that connection. Its gold standard of evaluation is the study of heart rate variability (HRV). To investigate whether any association exists between the HRV parameters and sub-threshold depressive symptoms in a sample of healthy subjects., Method: In this cross-sectional study, two short-term HRV recordings (5 min - supine and sitting) have been analyzed in 77 healthy subjects. Here we adopted a three-fold approach to evaluate HRV: a set of scores belonging to the time domain; to the frequency domain (high, low, and very low frequencies) and a set of 'nonlinear' parameters. The PHQ-9 (Patient Health Questionnaire-9) scale was used to detect depressive symptoms., Results: Depressive symptoms were associated only with a parameter from the non-linear approach and specifically the long-term fluctuations of fractal dimensions (DFA-α2). This association remained significant even after controlling for age, gender, BMI (Body-Mass-Index), arterial hypertension, anti-hypertensive drugs, dyslipidemia, and smoking habits. Moreover, the DFA-α2 was not affected by the baroreflex (postural change), unlike other autonomic markers., Conclusions: Fractal analysis of HRV (DFA-α2) allows then to predict depressive symptoms below the diagnostic threshold in healthy subjects regardless of their health status. DFA-α2 may be considered as an imprint of subclinical depression on the heart rhythm., Competing Interests: Competing interests: None., (© 2022 Giovanni Fioriti Editore s.r.l.)

Background: Heart rate variability (HRV), a measure of autonomic function, has been associated with both cardiovascular disease and cognitive dysfunction. In turn, cardiovascular risk has been linked to an increased risk of dementia onset. However, whether autonomic dysfunction may represent an early marker of cognitive decline in individuals with high cardiovascular risk is still an open issue., Methods: We performed a complete 24-hour HRV analysis in 50 middle-aged and elderly subjects with cardiovascular risk as assessed with the European Society of Cardiology Systematic Coronary Risk Evaluation (ESC SCORE). Cognitive performance was evaluated by Montreal Cognitive Assessment (MoCA), Free and Cued Selective Reminding Test (FCSRT) and Stroop Color and Word Test. Stepwise regression was used to identify significant associations between 24-hour ambulatory ECGs parameters and cognitive performances., Results: There were 30 women and 20 men with mean age of 64.9 years (range 51-77) and the mean ESC SCORE was 6%. Four subjects were diagnosed with mild cognitive impairment. Associations were found between measures of HRV and measures of cognition. Ultra-low frequency (ULF) band power of HRV significantly correlated with MoCA (r = 0.424, p = 0.003), also after adjustment for demographics and education. A significant association was also found between the ESC SCORE and ULF band power (r = -0.470, p = 0.0009)., Conclusions: Ultra-low frequency band power of HRV is associated with cognitive performance of middle-aged and elderly subjects with cardiovascular risk. This finding may indicate that autonomic nervous system dysregulation plays a role in developing cardiovascular risk and cognitive decline., Competing Interests: None of the authors have any conflicts of interest to declare., (© 2022 The Author(s).)

Aims: Fabry cardiomyopathy is characterized by glycosphingolipid storage and increased myocardial trabeculation has also been demonstrated. This study aimed to explore by cardiac magnetic resonance whether myocardial trabecular complexity, quantified by endocardial border fractal analysis, tracks phenotype evolution in Fabry cardiomyopathy., Methods and Results: Study population included 20 healthy controls (12 males, age 32±9) and 45 Fabry patients divided into three groups: 15 left ventricular hypertrophy (LVH)-negative patients with normal T1 (5 males, age 28±13; Group 1); 15 LVH-negative patients with low T1 (9 males, age 33±9.6; Group 2); 15 LVH-positive patients (11 males, age 53.5±9.6; Group 3). Trabecular fractal dimensions (Dfs) (total, basal, mid-ventricular, and apical) were evaluated on cine images. Total Df was higher in all Fabry groups compared to controls, gradually increasing from controls to Group 3 (1.27±0.02 controls vs. 1.29±0.02 Group 1 vs. 1.30±0.02 Group 2 vs. 1.34±0.02 Group 3; P<0.001). Group 3 showed significantly higher values of all Dfs compared to the other Groups. Both basal and total Dfs were significantly higher in Group 1 compared with controls (basal: 1.30±0.03 vs. 1.26±0.04, P =0.010; total: 1.29±0.02 vs. 1.27±0.02, P=0.044). Total Df showed significant correlations with: (i) T1 value (r=-0.569; P<0.001); (ii) LV mass (r=0.664, P<0.001); (iii) trabecular mass (r=0.676; P <0.001); (iv) Mainz Severity Score Index (r=0.638; P<0.001)., Conclusion: Fabry cardiomyopathy is characterized by a progressive increase in Df of endocardial trabeculae together with shortening of T1 values. Myocardial trabeculation is increased before the presence of detectable sphingolipid storage, thus representing an early sign of cardiac involvement., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Kounis syndrome is a hypersensitivity coronary disorder induced by exposure to several triggers; the most common are antibiotics, followed by insect bites., Methods: We reviewed the literature and identified 66 patients who experienced acute coronary syndrome after insect bites., Results: The median age was 51 years, and 19.0% were women and only 12% had a history of allergy. The most involved insects were bee and wasp (86%) and the most frequent clinical manifestations were chest pain and anaphylaxis (36% and 29%, respectively). ST-segment elevation was the most common electrocardiographic finding (>70%). There was a not negligible rate of complications (15%), with a possible increased arrhythmic burden in patients without significant coronary atherosclerosis., Conclusions: Acute coronary syndrome after insect bites is not so rare and it could have serious complications, with a possible increased arrhythmic burden in patients without significant coronary atherosclerosis.

Objective: The study is an explorative investigation aimed to assess the differences in acute stress response patterns of health workers facing coronavirus disease 2019 (COVID-19) during Italy's first lockdown., Methods: A cross-sectional investigation using convenience sampling method was conducted in Italy during April 2020. Eight hundred fifty-eight health workers participated in the research filling out self-report measures including Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7), Insomnia Severity Index (ISI), and Impact of Event Scale-Revised (IES-R)., Results: Moderate/severe depression was found in 28.9% (95% CI, 25.8-32.04), moderate/severe anxiety in 55.4% (95% CI, 51.9-58.8), insomnia in 15% (95% CI, 12.5-17.5), and distress in 52.5% (95% CI, 48.5%-56.6) of participants. The 3% of health workers reported frequent suicidal thoughts. Female sex, working for >15 h/week in a COVID-19 unit, and living apart from family were associated with a significantly higher risk of distress, anxiety, insomnia, depression, and functional impairment. Four profiles were identified on the basis of psychopathological measures: Profile&#95;0 included 44% ( N = 270); Profile&#95;1, 25.6% ( N = 157); Profile&#95;2, 19.1% ( N = 117); and Profile&#95;3, 11.3% ( N = 69) of participants. Results showed a significant effect for Profiles X IES-R (η 2 = 0.079; f = 0.29), indicating that in all profiles, except for Profile&#95;0, avoidance scale is lower than hyperarousal and intrusion symptoms scales of the IES-R. This characteristic could be a probable index of the control exerted by the responders to not fly away from their job., Conclusion: The identification of specific profiles could help psychiatrists and emergency psychologists to build specific interventions in terms of both primary and secondary prevention to face future waves of the COVID-19 outbreak., 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 © 2021 Moderato, Lazzeroni, Oppo, Dell’Orco, Moderato and Presti.)

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.

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 ± 11years, 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.

Background: In many genetic and acquired non-ischaemic cardiomyopathies (NICM) there have been frequent reports of involvement of the interventricular septum (IVS) by late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR). However, no studies have investigated the relationship between septal LGE and arrhythmias in different NICM subtypes., Methods: This study enrolled 103 patients with septal LGE at baseline CMR and different NICM: hypertrophic (n=29) or lamin A/C gene (LMNA)-associated (n=23) cardiomyopathy, and acute (n=30) or previous (n=21) myocarditis. During follow-up, the occurrences of malignant ventricular arrhythmias (MVA) and major bradyarrhythmias (BA) were evaluated., Results: At 4.9±0.7 years of follow-up, the occurrence of MVA and major BA in genetic vs acquired NICM were 10 of 52 vs 12 of 51, and 10 of 52 vs 4 of 51, respectively (both p=n.s.). However, MVA occurred more frequently in LMNA-NICM (eight of 23 vs two of 29 hypertrophic, p=0.015) and in previous myocarditis (nine of 21 vs three of 30 acute, p=0.016), while major BAs were particularly common in LMNA-NICM patients only (nine of 23 vs one of 29 hypertrophic, p=0.003). Different patterns of septal LGE were consistently retrospectively identified at baseline CMR: junctional and limited to the base in 79.3% of uneventful hypertrophic NICM; extended and focally transmural in LMNA-NICM with follow-up arrhythmias (both p<0.05); transitory in patients with acute myocarditis, who, differently from the post-myocarditis ones, showed follow-up arrhythmias only in the presence of unmodified LGE at follow-up CMR (five of 13, p=0.009)., Conclusion: Septal LGE was significantly associated with MVA at the 5-year follow-up in LMNA-NICM or previous myocarditis, and with major BA in LMNA-NICM only. These differences correlated with heterogeneous patterns of IVS LGE in different NICM., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Recent developments of detrended fluctuation analysis (DFA) provide multifractal/multiscale (MFMS) descriptions of the heart rate self-similarity, a promising approach to cardiovascular complexity. However, it is unclear whether the MFMS DFA may also describe the nonlinear components of heart rate variability. Our aim is to define MFMS DFA indices for quantifying the short-term and long-term degree of the heart-rate nonlinearity and to apply these indices to detect possible sex-related differences.We recorded the inter-beat-interval (IBI) series in 42 male and in 42 female healthy participants sitting at rest for about 2 hours. For each series j, we generated 100 phase-randomized surrogate series. We applied the MFMS DFA to estimate the self-similarity coefficients α over scales τ between 8 and 512 s and moment orders q between -5 and +5, obtaining coefficients for the original series, α O,j (q, τ), and for each surrogate, α i,j (q, τ) with 1≤i≤100. We first evaluated π j (q, τ), percentile of α i,j (q, τ) distribution in which was α O,j (q, τ). Then we calculated the percentages of scales where π j (q, τ) was <5% for 8≤τ≤16 s (short-term nonlinearity index NL 1 (q)) and for 16≤τ≤512 s (long-term nonlinearity index NL 2 (q)). We found that NL 1 (q) was generally greater than 50% at all q≥0 but q=2 (i.e., moment order of the monofractal DFA), while at q<0 it was high in males only, with significant sex differences at q=-1 and q=-2. Results indicate that the multifractal DFA may highlight nonlinear heart-rate components at the short scales that are not revealed by the traditional monofractal DFA and that appear related to gender differences.Clinical Relevance- This supports the use of MFMS DFA to integrate the linear information from traditional spectral methods of heart rate variability in clinical studies aimed at improving the stratification of the cardiovascular risk.

Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the myocardium associated to mutations in sarcomeric genes, but the link between genotype and phenotype remains poorly understood. Magnetic resonance spectroscopy studies have demonstrated impaired cardiac energetics in patients with HCM, and altered mitochondria were described in biopsies, but little is known about possible perturbations of mitochondrial function and adenosine triphosphate (ATP) production/consumption. The aim of this study was to investigate possible abnormalities in mitochondrial enzymes generating/scavenging reactive oxygen species, and changes in the Ca 2+ -activated ATPases in myocardial tissue from patients with obstructive HCM undergoing surgical myectomy compared to unused donor hearts (CTRL). Methods and Results: Both the amount and activity of mitochondrial Complex I (nicotinamide adenine dinucleotide -reduced form, NADH, dehydrogenase) were upregulated in HCM vs. CTRL, whilst the activity of Complex V (ATP synthase) was not reduced and ATP levels were significantly higher in HCM vs. CTRL. Antioxidant Mn-activated superoxide dismutase (SOD2) and (m)-aconitase activities were increased in HCM vs. CTRL. The Cu/Zn-activated superoxide dismutase (SOD1) amount and mtDNA copy number were unaltered in HCM. Total Ca 2+ -activated ATPase activity and absolute amount were not different HCM vs. CTRL, but the ratio between ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting type 2 (ATP2A2) and type 1 (ATP2A1), ATP2A2/ATP2A1, was increased in HCM in favor of the slow isoform (ATP2A2). Conclusion: HCM is characterized by mitochondrial Complex I hyperactivity and preserved Ca 2+- activated ATPase activity with a partial switch towards slow ATP2A2. This data may give insight into the abnormal cellular energetics observed in HCM cardiomyopathy but other studies would need to be performed to confirm the observations described here.

Takotsubo syndrome (TTS) is one of the causes of myocardial infarction with non-obstructive coronary arteries, and is often triggered by physical events (e.g. acute respiratory failure), or emotional events (e.g. loss of a family member, cardiac stress induced by an acute illness). SARS-CoV-2 pneumonia currently represents a worldwide health problem; the correlations between cardiovascular disease, myocardial injury and SARS-CoV-2 infection are still unclear, but initial data show that myocardial damage represents a negative prognostic factor. Myocardial injury during SARS-CoV-2, as defined by a pathological rise in circulating troponin levels, is not an uncommon complication in hospitalized patients, and is significantly more frequent in intensive care unit patients and among those who died. In this setting, myocardial injury is mainly secondary to type 2 myocardial infarction (mismatch in myocardial oxygen supply and demand during respiratory failure); other causes include myocarditis, coronary thrombosis, sepsis or septic shock. At present, only few cases of TTS have been described during SARS-CoV-2. Here we report the case of a patient hospitalized for pneumonia and respiratory failure due to SARS-CoV-2 with subsequent onset of TTS triggered by both physical and emotional events.

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.

Left ventricular noncompaction (LVNC) is an increasingly recognised cardiomyopathy characterised by excessive trabeculation and deep intertrabecular recesses in direct communication with the left ventricular cavity. In LVNC, hypertrabeculation has been associated with heart failure, ventricular arrhythmia, and systemic thromboembolism. However, hypertrabeculation alone is not sufficient to define a subject as at risk for such complications and thus should not be sufficient to diagnose LVNC. Despite several studies having investigated parameters to predict adverse cardiovascular events, physicians have no effective tools to differentiate between clinically silent hypertrabeculation and LVNC. The aim of this paper was to review literature on LVNC diagnostic criteria and to provide an easy and accessible diagnostic algorithm to distinguish between hypertrabeculation phenotype, non-compaction phenotype and LVNC cardiomyopathy.

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 ± 26 months 939 subjects with available QRS and T axis data; mean age was 68 ± 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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Although a substantial reduction in post-myocardial infaction mortality has been obtained in recent decades, one-year mortality rates are still high and 20% of patients who survive after the acute phase suffer a second cardiovascular event in the first year. In the setting of secondary cardiovascular prevention, the long-term cardiovascular risk stratification represents one of the most interesting and charming challenge for physician. Lifestyle changes and long-term control of traditional cardiovascular risk factors remain the cornerstone of secondary cardiovascular prevention and continue to offer the most powerful prognostic implications in the field of preventive cardiology with strong evidence of reduction in mortality and morbidity. In this regard, clinical, ECG, echocardiographic, cardiopulmonary exercise test data as well as biochemical markers of adverse prognosis are useful tool to identify patients at risk of developing future cardiovascular events. An integrated approach based on the analysis of all cardiovascular risk factors (traditional and emerging) along with instrumental and laboratory data represents the better way to predict prognosis in secondary cardiovascular prevention.

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.

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.

Background Abnormal P-wave axis has been correlated with an increased risk of all-cause and cardiovascular mortality in a general population. We aimed to evaluate the prognostic role of abnormal P-wave axis in patients undergoing myocardial revascularisation or cardiac valve surgery. Methods We considered data of 810 patients with available P-wave axis measure from a prospective monocentric registry of patients undergoing cardiovascular rehabilitation. A total of 436 patients (54%) underwent myocardial revascularisation, 253 (31%) valve surgery, 71 (9%) combined valve and coronary artery bypass graft surgery and 50 (6%) cardiac surgery for other cardiovascular disease. Mean follow-up was 47 ± 27 months. Results Over the whole group, P-wave axis was 43.8° ± 27.5° and an abnormal P-wave axis was found in 94 patients (12%). The risk of overall (hazard ratio (HR) 2.5, 95% confidence interval (CI) 1.6-4.0, P < 0.001) and cardiovascular mortality (HR 2.9, 95% CI 1.5-5.8, P = 0.002) was significantly higher in patients with abnormal P-wave axis even after adjustment for age, other electrocardiographic variables (PR, QRS, QTc intervals), left ventricular ejection fraction and left atrial volume index. After dividing the population according to the type of disease, patients with abnormal P-wave axis and ischaemic heart disease had 3.9-fold higher risk of cardiovascular mortality (HR 3.9, 95% CI 1.3-12.1, P = 0.017), while a 2.2-fold higher risk of cardiovascular mortality (HR 3.6, 95% CI 1.3-10.1, P = 0.015) was found in those with cardiac valve disease. Conclusion An abnormal P-wave axis represents an independent predictor of both overall and cardiovascular mortality in patients undergoing myocardial revascularisation or cardiac valve surgery.