Background: The association of sex hormone-binding globulin (SHBG) with heart failure (HF) remains a topic of ongoing debate, particularly in the light of type 2 diabetes mellitus (T2DM). We aimed to assess the association of SHBG with clinical and echocardiographic parameters of HF in men according to the presence of T2DM. Methods: Data on baseline characteristics, cardiovascular risk factors and medications, laboratory findings including serum SHBG and total testosterone concentrations, and echocardiographic parameters were prospectively collected for 215 male patients consecutively hospitalized for an acute episode of HF. Results: Patients with T2DM were older (p = 0.013), had a greater body mass index (p = 0.009) and NYHA class (p = 0.001), and were more likely to have hypertension (p < 0.001) or hyperlipidemia (p = 0.032). A moderate correlation among SHBG and total testosterone with the left ventricular ejection fraction (LVEF) was observed only in T2DM patients (r = 0.456) but not among non-T2DM patients (r = 0.194). A multivariate analysis revealed the independent association of increased SHBG levels with lower LVEF values among T2DM patients (ß = -0.542, p < 0.0001), whereas in the same group higher total testosterone was an independent predictor of higher LVEF (ß = 0.531, p < 0.0001) and lower LVDD (ß = -0.442, p = 0.0002) levels. Conclusions: In men with HF and T2DM, in contrast to testosterone, SHBG may have an independent adverse impact on the LVEF, which may account for 12.5% of the variance in LVEF levels. The possible subcellular mechanisms of SHBG in men with diabetic myocardial disorder should be additionally explored.

A multiple hormonal imbalance that accompanies heart failure (HF) may have a significant impact on the clinical course in such patients. The non-thyroidal illness syndrome (NTIS), also referred to as euthyroid sick syndrome or low triiodothyronine syndrome, can be found in about 30% of patients with HF. NTIS represents a systemic adaptation to chronic illness that is associated with increased cardiac and overall mortality in patients with HF. While conclusions on thyroid-stimulating hormone, free triiodothyronine, total and free thyroxine are currently unresolved, serum total triiodothyronine levels and the ratio of free triiodothyronine to free thyroxine seem to provide the best correlates to the echocardiographic, laboratory and clinical parameters of disease severity. HF patients with either hyper- or hypothyroidism should be treated according to the appropriate guidelines, but the therapeutic approach to NTIS, with or without HF, is still a matter of debate. Possible treatment options include better individual titration of levothyroxine therapy, combined triiodothyronine plus thyroxine therapy and natural measures to increase triiodothyronine. Future research should further examine the cellular and tissue mechanisms of NTIS as well as new therapeutic avenues in patients with HF.

Journal Article Corrected proof Exercise training and regression of coronary atheromatous plaques Get access Viktor Čulić Viktor Čulić Department of Cardiology and Angiology, University Hospital Centre Split, Šoltanska 1, Split 21000, CroatiaDepartment of Clinical Propedeutics, University of Split School of Medicine, Šoltanska 2, Split 21000, Croatia Corresponding author. Tel: +385 21 55 72 89, Fax: +385 21 55 73 85, Email: viktor.culic@st.t-com.hr https://orcid.org/0000-0002-4026-0195 Search for other works by this author on: Oxford Academic Google Scholar European Journal of Preventive Cardiology, zwad215, https://doi.org/10.1093/eurjpc/zwad215 Published: 28 June 2023 Article history Published: 28 June 2023 Corrected and typeset: 01 July 2023

aDepartment of Cardiology and Angiology, University Hospital Centre Split bUniversity of Split School of Medicine, Split, Croatia cDivision of Cardiology, McGill University Health Centre, Montreal, Quebec, Canada Correspondence to Prof. Viktor Čulić, Department of Cardiology and Angiology, University Hospital Centre Split, Šoltanska 1, 21000 Split, Croatia Tel: +385 21 55 72 89; fax: +385 21 55 73 85; e-mail: [email protected] Received 14 January, 2024 Revised 19 June, 2024 Accepted 24 June, 2024

Lay Summary Twelve case-crossover studies with 19 891 patients were included in our systematic review with meta-analysis to estimate how many acute myocardial infarctions may be attributed to bouts of physical exertion and to explore possible modifiers of this association.Approximately 10.6% of all acute myocardial infarctions may be attributed to physical exertion, but the impact was greater in younger individuals or those engaged in exertion one to three times/week. Among the latter, exertion triggers approximately every fifth infarction.Beta-blockers may provide a protection from the triggering effect of physical exertion. Aims While regular physical activity has clear benefits to cardiovascular health, physical exertion can trigger acute myocardial infarction (AMI). We aimed to estimate how many AMIs may be attributed to bouts of physical exertion and to explore possible modifiers of this association. Methods and results MEDLINE, ISI Web of Science, and Scopus databases were searched for case-crossover studies reporting the relative risk (RR) of exertion-related AMI and exposure prevalence in the control periods. We used the random-effects model to pool the RR estimates and the mixed-effects model and random-effects meta-regression for subgroup analyses and estimated the population attributable fraction (PAF) at the population level and in different subgroups. The study met the Preferred Reporting Items for Systematic Reviews and Meta-Analyses requirements. Twelve studies including 19 891 AMI patients met the criteria for inclusion. There was a strong overall association between episodic physical exertion and AMI [RR = 3.46; 95% confidence interval (CI), 3.16-3.78]. The total PAF was 10.6% (95% CI, 9.44-11.83). For each additional year of age, the RR of exertion-related AMI increased by similar to 3%, but the PAF decreased by 2%. For each additional time of habitual activity per week, the RR of exertion-related AMI decreased by similar to 43%. The impact was greater among those engaged in physical exertion one to three times a week (>= 20% of cases) and among those who did not take compared with those who took beta-blockers (P = 0.049). Conclusion Every tenth AMI may be assigned to physical exertion. The impact was more pronounced among younger patients, those exposed to exertion one to three times a week, and those not taking beta-blockers.

COVID-19-associated vascular disease complications are primarily associated with endothelial dysfunction; however, the consequences of disease on vascular structure and function, particularly in the long term (>7 weeks post-infection), remain unexplored. Individual pre- and post-infection changes in arterial stiffness as well as central and systemic hemodynamic parameters were measured in patients diagnosed with mild COVID-19. As part of in-laboratory observational studies, baseline measurements were taken up to two years before, whereas the post-infection measurements were made 2–3 months after the onset of COVID-19. We used the same measurement protocol throughout the study as well as linear and mixed-effects regression models to analyze the data. Patients (N = 32) were predominantly healthy and young (mean age ± SD: 36.6 ± 12.6). We found that various parameters of arterial stiffness and central hemodynamics—cfPWV, AIx@HR75, and cDBP as well as DBP and MAP—responded to a mild COVID-19 disease. The magnitude of these responses was dependent on the time since the onset of COVID-19 as well as age (pregression_models ≤ 0.013). In fact, mixed-effects models predicted a clinically significant progression of vascular impairment within the period of 2–3 months following infection (change in cfPWV by +1.4 m/s, +15% in AIx@HR75, approximately +8 mmHg in DBP, cDBP, and MAP). The results point toward the existence of a widespread and long-lasting pathological process in the vasculature following mild COVID-19 disease, with heterogeneous individual responses, some of which may be triggered by an autoimmune response to COVID-19.

Heart failure (HF) is a multiple hormonal deficiency syndrome which includes alterations in the serum concentration of thyroid hormones (TH). This cross-sectional study enrolled 215 male patients hospitalised for acute HF. Data on cardiovascular risk factors, chronic medications, cardiac function assessed by echocardiography, and clinical parameters of HF were prospectively collected. The independent predictive association of TH with all investigated parameters of the HF severity were assessed. The patient’s mean age was 74.4 years, 57.2% had arterial hypertension, 54.0% were consuming alcohol, and 42.3% were diabetics. Multivariate analysis revealed that total triiodothyronine (TT 3 ) was an independent predictor of greater left ventricular ejection fraction (LVEF; β = 0.223, p = 0.008), less progressed left ventricular diastolic dysfunction (LVDD; β = − 0.271, p = 0.001) and lower N-terminal pro-brain natriuretic peptide (NT-proBNP; β = − 0.365, p < 0.001). None of the TH other than TT 3 was associated with LVDD or NT-proBNP, whereas free triiodothyronine ( β = − 0.197, p = 0.004), free thyroxine ( β = − 0.223, p = 0.001) and total thyroxine ( β = − 0.140, p = 0.041) were inversely associated with LVEF. The present study suggests that, among TH, serum TT 3 level is most closely associated with echocardiographic, laboratory and clinical parameters of the severity of HF in men.

Background and purpose: Subcutaneous implantable cardioverter defibrillators (S-ICDs) have emerged in recent years as a valid alternative to traditional transvenous ICDs (TV-ICDs). Therefore, the number of S-ICD implantations is rising, leading to a consequent increase in S-ICD-related complications sometimes requiring complete device removal. Thus, the aim of this systematic review is to gather all the available literature on S-ICD lead extraction (SLE), with particular reference to the type of indication, techniques, complications and success rate. Methods: Studies were identified by searching electronic databases (Medline via PubMed, Scopus and Web of Science) from inception to 21 November 2022. The search strategy adopted was developed using the following key words: subcutaneous, S-ICD, defibrillator, ICD, extraction, explantation. Studies were included if they met both of the following criteria: (1) inclusion of patients with S-ICD; (2) inclusion of patients who underwent SLE. Results: Our literature search identified 238 references. Based on the abstract evaluation, 38 of these citations were considered potentially eligible for inclusion, and their full texts were analyzed. We excluded 8 of these studies because no SLE was performed. Eventually, 30 studies were included, with 207 patients who underwent SLE. Overall, the majority of SLEs were performed for non-infective causes (59.90%). Infection of the device (affecting either the lead or the pocket) was the cause of SLE in 38.65% of cases. Indication data were not available in 3/207 cases. The mean dwelling time was 14 months. SLEs were performed using manual traction or with the aid of a tool designed for transvenous lead extraction (TLE), including either a rotational or non-powered mechanical dilator sheath. Conclusions: SLE is performed mainly for non-infective causes. Techniques vary greatly across different studies. Dedicated tools for SLE might be developed in the future and standard approaches should be defined. In the meantime, authors are encouraged to share their experience and data to further refine the existing variegated approaches.

INTRODUCTION: Coagulopathy, in the form of either venous or arterial thromboembolism, is one of the most severe sequelae of coronavirus disease (COVID-19) and has been associated with poorer outcomes. However, the role of therapeutic anticoagulation (tAC) or prophylactic anticoagulation (pAC) in COVID-19 patients has not been definitely established. Therefore, the aim of this systematic review and meta-analysis was to gather all the available real-world data in the field and to provide a reliable effect size of the effect on mortality of tAC compared to pAC in COVID-19 patients.EVIDENCE ACQUISITION: Real-world studies (RWS) were identified by searching electronic databases from inception to 31st October, 2021. Randomized controlled trials were excluded. Mortality and bleedings were considered as primary and secondary outcomes, respectively.EVIDENCE SYNTHESIS: 10 RWS and 5541 patients were included in the analysis. Overall, tAC was associated with lower mortality (HR=0.62, 95% CI: 0.54-0.71). There was asymmetry at the funnel plot suggesting publication bias, that was not confirmed at the Egger test (P=0.07). For the secondary endpoint, there was a non-statistically significant tendency for more bleedings in patients treated with tAC compared to pAC (RR=1.75, 95% CI: 0.81-3.81).CONCLUSIONS: Our meta-analysis, based on RWS and adjusted estimates of risk, suggests a survival benefit of tAC over pAC in COVID-19 patients in the real world.