The role of a prothrombotic state in atrial fibrillation (AF) progression to permanent arrythmia (PerAF) is unclear. Formation of denser and poorly lysable fibrin clots has been observed in AF patients also with sinus rhythm in association with higher stroke risk. We investigated whether altered fibrin clot properties and other prothrombotic state markers may contribute to AF transition to PerAF.
In the cohort study, in 226 anticoagulated patients (median age 69 years, median CHA2DS2-VASc of 3) with paroxysmal (n = 83, 36.7%) or persistent (n = 143, 63.3%) AF, we assessed at baseline plasma clot permeability (Ks), clot lysis time (CLT), proteins involved in fibrinolysis and von Willebrand factor (vWF) antigen. We recorded patients with PerAF during a median follow-up of 58 months.
During follow-up, PerAF was documented in 62 (27.4%, 5.7%/year) subjects, who had higher prevalence of heart failure, higher body mass index and longer history of arrhythmia. AF transition to PerAF was associated with 25.7% longer CLT in relation to 21.3% higher plasminogen activator inhibitor type 1, and 29% higher vWF compared to the remainder, with no differences in Ks, plasminogen or α2-antiplasmin. By multivariable analysis, CLT (per 10 min, odds ratio [OR] 2.734, 95% confidence interval [CI] 1.788–4.180, p < .001), vWF (per 10%, OR 1.352, 95% CI 1.145–1.596, p < .001) and heart failure (OR 2.637, 95% CI 1.008–6.900, p = .048) were associated with progression to PerAF.
Suppressed fibrin clot susceptibility to lysis and elevated vWF could contribute to progression to PerAF despite anticoagulation, which suggests links between blood coagulation and AF progression.
Meteorin-like protein (Metrnl) has been recently suggested as a new adipokine with protective cardiovascular effects. Its circulating levels in patients seem to be associated with heart failure (HF), although with contradictory results. Our aim was to ascertain whether this adipokine could estimate the prognosis of HF in de novo HF (DNHF) patients.
Metrnl plasma levels of 400 patients hospitalized with DNHF (55% of patients with HF with reduced ejection fraction, 17.3% HF with mid-range ejection fraction, 27.8% HF with preserved ejection fraction) were measured by enzyme-linked immunosorbent assay. We performed both sex-pooled and sex-specific analyses. A 12-month follow-up was conducted, during which clinical outcomes such as all-cause mortality, cardiovascular death and re-hospitalization due to HF were collected.
After a 12-month follow up, higher plasma Metrnl levels were associated with an increased risk for all-cause death and cardiovascular death after adjusting by sex, age, LVEF, hypertension, diabetes, ischemic aetiology, chronic renal failure, NT-proBNP and troponin (hazard ratio [HR] = 1.003, 95% confidence interval [CI] = 1.000–1.005; p-value<.05 and HR = 1.004, 95% CI = 1.001–1.007, p-value<.05, respectively). In line with this, DNHF patients with increased levels of circulating Metrnl had a higher number of occurrences of cardiovascular events. Regarding Metrnl associations with parameters implicated in the development and progression of HF, we found that Metrnl circulating levels were positively correlated with age (r = .322, p-value<.0001), NT-proBNP (r = .281, p-value<.0001) and with the renal dysfunction markers urea (r = .322, p-value<.0001) and creatinine (r = .353, p-value<.0001) and higher in women than men (473.7 [385.9–594.0] pg/mL vs. 428.7 [349.1–561.3] pg/mL, p-value<.006). Finally, concerning the subtype of HF, Metrnl plasma levels were higher in HF with preserved ejection fraction.
Patients with higher Metrnl levels have a worse prognosis in DNHF. Our results reinforce the association of Metrnl plasma levels with HF progression and outcomes.
Steroid hormones are key mediators of adaptative responses to exercise, a stimulus that may concurrently affect their blood concentrations. However, the chronic endocrine adaptations and whether these potential changes are dependent on exercise intensity remain undetermined. Moreover, it is also unknown if the exercise-induced effects on steroid hormonal status are related to the participant' sex.
This study aimed to investigate the intensity effects of a 24-week supervised concurrent training intervention on steroid hormones in sedentary young men and women. A total of 106 untrained young adults (68% women) aged 18–25 years were randomly assigned to one of the three groups: (I) Control group (no exercise; n = 35); (II) Ex-Moderate group (concurrent training at moderate intensity; n = 36); (III) Ex-Vigorous group (concurrent training at vigorous intensity; n = 35). Steroid hormones (i.e. cortisol, testosterone and dehydroepiandrosterone sulfate (DHEAS)) were measured in plasma through a chemiluminescent method. Body composition parameters were determined using a dual-energy X-ray absorptiometry scanner.
No significant changes in steroid hormones levels were observed after the intervention (all p ≥ .129). However, a time x group interaction was noted in the testosterone/cortisol ratio (T/C ratio) only in women (p = .044). Concretely, our data showed a significant decrement of T/C ratio in both the Ex-Moderate group and in the Ex-Vigorous compared with the control group (Δ = −24.2 ± 2.0% and Δ = −38.9 ± 45.4%, respectively).
Our 24-week supervised concurrent training intervention showed no significant changes in steroid hormone levels. However, a significant decrement of T/C ratio was observed only in women, indicating a sexual dimorphism in the effect on T/C ratio.
Sotatercept binds free activins by mimicking the extracellular domain of the activin receptor type IIA (ACTRIIA). Additional ligands are BMP/TGF-beta, GDF8, GDF11 and BMP10. The binding with activins leads to the inhibition of the signalling pathway and the deactivation of the bone morphogenic protein (BMP) receptor type 2. In this way, sotatercept activates an antiproliferative signalling to the cells of the pulmonary arteries and arterioles with the aim of rebalancing the proliferative and antiproliferative pathway that characterizes the pulmonary arterial hypertension (PAH). Sotatercept is indicated for the treatment of group 1 PAH in combination with drugs that act through the endothelin receptor, nitric oxide or prostacyclin. Its effects, demonstrated in the STELLAR study, are the improvement of exercise capacity and the FC-WHO functional class, together with the reduction of the risk of clinical worsening events. In addition to its antiremodeling effects on the pulmonary circulation, sotatercept has several haematological effects that could suggest its use in the treatment of some blood disorders other than PAH. In this review, we will discuss the effects of the drug on PAH and in parallel provide an in-depth overview of its application in haematological disorders, focusing on clinical and preclinical studies.
Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), is a potentially fatal disease with a multifactorial nature, impacting different medical and surgical specialties. Recently, new guidelines and direct oral anticoagulants facilitated early discharge for most DVT patients and non-severe PE patients.
The aim of this study is to illustrate the distribution of VTE patients throughout the hospital and map their care pathway from Emergency Department (ED) to hospital discharge.
This multicenter retrospective cross-sectional study included all hospitalized patients with a VTE code from 39 hospitals between 2018 and 2019. Data were analysed using JupyterLab, with subgroup analyses based on mode of entry, diagnosis location and thrombosis site.
A total of 23,199 hospitalizations were analysed, involving 17,718 patients a median age 66 years [52–78] and man-to-women ratio 1.05. Among these, 10,747(46.3%) had PE and 4176(18.0%) had lower limb DVT. The ED was the primary entry point for 31.2% of cases, followed by gastroenterology, surgery, geriatrics, and internal medicine. Patients admitted through ED patients were most frequently transferred to internal medicine, cardiovascular and intensive care units (ICU). The median hospital stay was 9 days [4–21], with ICU stays being the longest (mean 15 days [8–27]). Notably, 1357 patients (18.8%) of VTE patients were discharged within 48 h of ED admission.
This study is the first to portray the distribution and care pathways of VTE patients across hospital departments. Despite recent clinical guidelines, many patients still require inpatient management, highlighting the need for dedicated care pathway.
Coronary artery disease (CAD) and atrial fibrillation (AF) often coexist, but the impact of clinical phenotypes of CAD on outcomes in AF patients in the non-vitamin K antagonist oral anticoagulant drugs (NOACs) era is less well understood.
This was a post-hoc of the GLORIA-AF registry, a global, multicenter, prospective AF registry study. Patients were divided into three groups: prior history of myocardial infarction (MI)/unstable angina group (Group 1); stable angina group (Group 2); and a control group without stable angina or history of MI/unstable angina. The primary endpoint was the composite of all-cause death or stroke, and the safety endpoint was major bleeding.
A total of 24,827 patients were included in this analysis (median age was 71 (IQR, 64–78) years; 55% male) and 5394 (21.7%) had CAD. During a follow-up of 2 years, the incidence of the primary endpoint was 5.99 (95% CI, 5.33, 6.71) per 100 patient-years in Group 1, 4.04 (95% CI, 3.55, 4.70) per 100 patient-years in Group 2, and 2.79 (95% CI, 2.62, 2.96) per 100 patient-years in the control group (p < .001). Compared the control group, the adjusted hazard ratio of the primary composite endpoint in Groups 1 and 2 were 1.58 (95% CI, 1.37, 1.83, p < .001) and 1.22 (95% CI, 1.04, 1.43, p = .012), respectively. Among anticoagulated patients with AF and CAD, NOACs were associated with a reduced risk of the primary composite endpoint and major bleeding, compared with vitamin K antagonists (VKA).
CAD was prevalent in patients with AF, and clinical phenotypes of CAD influenced outcomes in patients with AF, with a history of MI/unstable angina being associated with a significantly increased risk of CV events, compared to stable angina. NOACs were superior to VKA in terms of the effectiveness and safety outcomes in patients with AF and concomitant CAD.
Introduction: Long-term fasting (LF) activates an adaptative response to switch metabolic fuels from food glucose to lipids stored in adipose tissues. The increase in free fatty acid (FFA) oxidation during fasting triggers health benefits. We questioned if the changes in lipid metabolism during LF could affect lipids in cell membranes in humans. We thus analysed the FA composition in erythrocyte membranes (EM) during 12.6 ± 3.5 days of LF and 1 month after food reintroduction.
Methods: A total of 98 subjects out of three single-arm interventional studies underwent a medical supervised long-term fasting (12.6 ± 3.5 days) programme. The distribution pattern of 26 FA as well as the HS-Omega-3 Index were assessed in the EM using gas chromatography.
Results: Eighteen of 26 FA showed significant changes. Within the group of saturated FA, myristic (14:0) and stearic acid (18:0) decreased while palmitic (16:0) and arachid acid (20:0) increased. While most monounsaturated FA increased, trans fatty acids decreased or remained unchanged. Within the polyunsaturated FA, arachidonic (20:4n6) and docosahexaenoic (22:6n3) acid increased, while linoleic (18:2n6), alpha-linolenic (18:3n3) and eicosapentaenoic acid (20:5n3) decreased. Consequently, the HS-Omega-3 Index increased. 11 out of the 18 FA with significant changes returned to baseline levels 1 month afterwards. Levels of linoleic and alpha-linolenic acid increased over baseline levels.
Conclusions: Long-term fasting triggers changes in the FA composition of EM.
Four scores have been published in 2022 for assessing mortality risk of patients with tricuspid regurgitation (TR): the TRI-SCORE, those reported by Hochstadt and Wang and the TRIO score. Our objective was to perform an external validation of available scores for predicting mortality and the combined endpoint of mortality and heart failure (HF) admission, in an independent cohort of patients with severe TR and to compare their discriminative ability.
Discriminative ability of the scores for predicting events was assessed by means of receiver operating characteristics (ROC) curves.
The validation cohort retrospectively included 614 consecutive patients (69 ± 13 years, 72% women) with severe TR studied with echocardiography in a tertiary care hospital and followed for up to 14 years (median 5 years, p25-75 2–7 years), with 358 deaths and 620 HF admissions on follow-up. Discriminative abilities for predicting death (C-statistic .72 [95% CI .68–.76] for the TRI-SCORE; .75 [.71–.78] for the Hochstadt score; .72 [.68–.76] for the Wang score; and .74 [.70–.78] for the TRIO score, p < .0005 for all) or the combined endpoint (C-statistic .74 [.70–.78]; .74 [.70–.78], .73 [.69–.77] and .76 [.72–.80], respectively, p < .0005 for all) on follow-up were statistically significant for all of them. Paired comparisons among them for predicting both endpoints were all non-significant.
All tested scores showed significant and similar discriminative ability for predicting the combined endpoint of mortality or HF admission in this independent validation study of patients with severe TR.
Background: The human microbiome is crucial in regulating intestinal and systemic functions. While its role in cardiovascular disease is better understood, the link between intestinal microbiota and valvular heart diseases (VHD) remains largely unexplored.
Methods: Peer-reviewed studies on human, animal or cell models analysing gut microbiota profiles published up to April 2024 were included. Eligible studies used 16S rRNA or shotgun sequencing, metabolite profiling by mass spectrometry, and examined osteogenesis or fibrosis signalling in valve cells. Methods and findings were qualitatively analysed, with data charted to summarize study design, materials and outcomes.
Results: Thirteen studies were included in the review: five human, three animal and five in vitro. Of the nine studies on calcific aortic stenosis (CAS), elevated trimethylamine N-oxide (TMAO) levels were linked to an increased risk of cardiovascular events in cohort studies, with CAS patients showing higher levels of Bacteroides plebeius, Enterobacteriaceae, Veillonella dispar and Prevotella copri. In vivo, TMAO promoted aortic valve fibrosis, while tryptophan derivatives stimulated osteogenic differentiation and interleukin-6 secretion in valvular interstitial cells. Two studies on rheumatic mitral valve disease found altered microbiota profiles and lower short-chain fatty acid levels, suggesting potential impacts on immune regulation. Two studies on Barlow's mitral valve disease in animal models revealed elevated TMAO levels in dogs with congestive heart failure, reduced Paraprevotellaceae, increased Actinomycetaceae and dysbiosis involving Turicibacter and E. coli.
Conclusions: TMAO has been mainly identified as a prognostic marker in VHD. Gut microbiota dysbiosis has been observed in various forms of VHD and deserve further study.
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