Atrial fibrillation (AF) patients with mid-range left ventricular ejection fraction (mrEF) of 40–49% have neither preserved (pEF > 50%) nor reduced (rEF < 40%) EF and are increasingly being ...recognized as a distinct group with specific clinical risks. We aimed to retrospectively investigate clinical characteristics and associated thrombotic, bleeding and mortality risks of mrEF in comparison to pEF and rEF in a cohort of 1000 non-valvular AF patients presenting in our institution during the period 2013–2018. Patients with mrEF presented with older age (
P
< 0.001) and a higher frequency of arterial hypertension (
P
= 0.001) in comparison to both pEF and rEF patients. In comparison to pEF, mrEF patients were more likely to have diabetes mellitus (
P
= 0.004), lower HDL-cholesterol (
P
< 0.001) and lower estimated glomerular filtration rate (
P
< 0.001), significantly higher CHA
2
DS
2
-VAS
C
score (
P
< 0.001), significantly higher HAS-BLED score (
P
= 0.002) and had a higher likelihood of receiving anticoagulant therapy, mostly warfarin (
P
= 0.001). In addition, mrEF patients had a significantly higher risk of thrombotic events (HR = 2.22;
P
= 0.015), death (HR = 1.71;
P
= 0.005) and composite endpoint of thrombosis, bleeding or death (HR = 1.65;
P
= 0.003) in comparison to pEF patients, but did not significantly differ in comparison to rEF patients. There was no significant difference regarding major bleeding risk. Associations with clinical outcomes remained statistically significant in multivariate models independently of CHA
2
DS
2
-VAS
C
. Our findings support defining AF patients with mrEF as a subgroup with distinct clinical characteristics and increased risk for thrombotic events and death, irrespective of predetermined CHA
2
DS
2
-VAS
C
risk. These patients seem to require special clinical considerations and more intensive control of cardiovascular risk factors.
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a respiratory illness named coronavirus disease 2019 (COVID-19), which is one of the main global health problems since 2019. ...Glycans attached to the Fc portion of immunoglobulin G (IgG) are important modulators of IgG effector functions. Fc region binds to different receptors on the surface of various immune cells, dictating the type of immune response. Here, we performed a large longitudinal study to determine whether the severity and duration of COVID-19 are associated with altered IgG glycosylation.
Using ultra-high-performance liquid chromatography analysis of released glycans, we analysed the composition of the total IgG N-glycome longitudinally during COVID-19 from four independent cohorts. We analysed 77 severe COVID-19 cases from the HR1 cohort (74% males, median age 72, age IQR 25-80); 31 severe cases in the HR2 cohort (77% males, median age 64, age IQR 41-86), 18 mild COVID-19 cases from the UK cohort (17% males, median age 50, age IQR 26-71) and 28 mild cases from the BiH cohort (71% males, median age 60, age IQR 12-78).
Multiple statistically significant changes in IgG glycome composition were observed during severe COVID-19. The most statistically significant changes included increased agalactosylation of IgG (meta-analysis 95% CI 0.03, 0.07, adjusted meta-analysis P= <0.0001), which regulates proinflammatory actions of IgG via complement system activation and indirectly as a lack of sialylation and decreased presence of bisecting N-acetylglucosamine on IgG (meta-analysis 95% CI -0.11, -0.08, adjusted meta-analysis P= <0.0001), which indirectly affects antibody-dependent cell-mediated cytotoxicity. On the contrary, no statistically significant changes in IgG glycome composition were observed in patients with mild COVID-19.
The IgG glycome in severe COVID-19 patients is statistically significantly altered in a way that it indicates decreased immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the severity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in COVID-19.
This work has been supported in part by Croatian Science Foundation under the project IP-CORONA-2020-04-2052 and Croatian National Centre of Competence in Molecular Diagnostics (The European Structural and Investment Funds grant #KK.01.2.2.03.0006), by the UKRI/MRC (Cov-0331 - MR/V027883/1) and by the National Institutes for Health Research Nottingham Biomedical Research Centre and by Ministry Of Science, Higher Education and Youth Of Canton Sarajevo, grant number 27-02-11-4375-10/21.
Objective: Stratifying patients with paroxysmal or short-term persistent atrial fibrillation (AF) who are at greater risk of developing permanent AF is challenging. Aim of our prospective study was ...to evaluate association of laboratory parameters (biochemistry and complete blood count (CBC)) together with standard demographic, clinical and echocardiography parameters, with AF progression.
Methods: We prospectively recruited 579 patients with AF and divided them into two groups at index hospitalization: paroxysmal or persistent (non-permanent AF), and long-term persistent or permanent AF patients (permanent AF). Clinical, echocardiographic, and relevant CBC parameters were collected. Non-permanent AF patients were selected for follow-up, with a median follow-up time of 21 months. Endpoint was progression to permanent AF.
Results: Out of 409 patients with non-permanent AF, 109 (26.6%) progressed within follow-up. In a multivariate Cox regression model only increased left atrium (LA) diameter (HR 2.16, 95% CI 1.20-3.87, p = 0.010), and increased red cell distribution width (RDW; HR 1.19, 95% CI 1.03-1.39, p = 0.022) showed significant independent association with progression. There were 221/409 patients with both LA ≤45 mm and RDW level ≤14.5% who progressed at a rate of only 17.6%, and showed relative risk of AF progression of 0.47 (95% CI 0.34-0.67; p < 0,001).
Conclusion: Together with LA size, RDW was independently associated with AF progression. Patients with both LA size ≤45 mm and RDW level ≤14.5% are most probably the best candidates for rhythm control strategies.
Heart failure (HF) with mid-range or mildly reduced ejection fraction (HFmrEF) is a separate clinical entity in the HF spectrum, with a left ventricular ejection fraction ranging from 40 to 49%. ...While sodium glucose co-transporter 2 inhibitors have become the cornerstone therapy for the entire HF spectrum, there are a few clinical trials of HFmrEF. This prospective observational study was conducted at Dubrava University Hospital, Zagreb, Croatia, from May 2021 to October 2023. We recruited 137 participants diagnosed with HFmrEF at admission. The majority were male, with a median age of 72 and overweight. A total of 110 participants were followed for 6 months and LVEF remained the same in the majority of patients (n = 62, 56.4%), improved in 32 patients (29.1%), and decreased in 3 patients (2.73%). A total of 64 participants were followed for 12 months: 39 remained the same (60.94%) and 25 improved. There were 13 deaths in (9.5%). While the empagliflozin group had a lower BMI at 6-month- and lower HbA1c at 12-month follow-up, there were no differences in death, HF hospitalizations, ER visits, or urinary tract infections in between groups. Despite recent and daily advances in the treatment of all HF phenotypes, HFmrEF still represents a challenge in everyday clinical practice.
There are few prospective data on the prognostic value of normal admission low-density lipoprotein cholesterol (LDL-C) in statin-naïve patients with acute coronary syndromes (ACS) who are treated ...with a preemptive invasive strategy. We aimed to analyze the proportion of patients with normal LDL-C at admission for ACS in our practice, and their characteristics and clinical outcomes in comparison to patients with high admission LDL-C.
Two institutions' prospective registries of patients with confirmed ACS from Jan 2017 to Jan 2023 were used to identify 1579 statin-naïve patients with no history of prior coronary artery disease (CAD), and with available LDL-C admission results, relevant clinical and procedural data, and short- and long-term follow-up data. Normal LDL-C at admission was defined as lower than 2.6 mmol/L. All demographic, clinical, procedural, and follow-up data were compared between patients with normal LDL-C and patients with a high LDL-C level (≥2.6 mmol/L) at admission.
There were 242 (15%) patients with normal LDL-C at admission. In comparison to patients with high LDL-cholesterol at admission, they were significantly older (median 67 vs. 62 years) with worse renal function, had significantly more cases of diabetes mellitus (DM) (26% vs. 17%), peripheral artery disease (PAD) (14% vs. 9%), chronic obstructive pulmonary disease (COPD) (8% vs. 2%), and psychological disorders requiring medical attention (19% vs. 10%). There were no significant differences in clinical type of ACS. Complexity of CAD estimated by coronary angiography was similar between the two groups (median Syntax score 12 for both groups). There were no significant differences in rates of complete revascularization (67% vs. 72%). Patients with normal LDL-C had significantly lower left ventricular ejection fraction (LVEF) at discharge (median LVEF 52% vs. 55%). Patients with normal LDL-C at admission had both significantly higher in-hospital mortality (5% vs. 2%, RR 2.07, 95% CI 1.08-3.96) and overall mortality during a median follow-up of 43 months (27% vs. 14%, RR 1.86, 95% CI 1.45-2.37). After adjusting for age, renal function, presence of diabetes mellitus, PAD, COPD, psychological disorders, BMI, and LVEF at discharge in a multivariate Cox regression analysis, normal LDL-C at admission remained significantly and independently associated with higher long-term mortality during follow-up (RR 1.48, 95% CI 1.05-2.09).
A spontaneously normal LDL-C level at admission for ACS in statin-naïve patients was not rare and it was an independent risk factor for both substantially higher in-hospital mortality and mortality during long-term follow-up. Patients with normal LDL-C and otherwise high total cardiovascular risk scores should be detected early and treated with optimal medical therapy. However, additional research is needed to reveal all the missing pieces in their survival puzzle after ACS-beyond coronary anatomy, PCI optimization, numerical LDL-C levels, and statin therapy.
Surgical repair for regurgitant bicuspid aortic valve (BAV) is promising but underutilized due to perceived complexities and lack of long-term data. This study evaluated the efficacy of valve-sparing ...root remodeling (VSRR) or isolated valve repair combined with calibrated external ring annuloplasty in BAV versus tricuspid aortic valve (TAV) patients. All patients operated on for aortic regurgitation and/or aneurysm at our institution between 2014 and 2022 were included and entered into the Aortic Valve Insufficiency and ascending aorta Aneurysm InternATiOnal Registry (AVIATOR). Patients with successful repair at index surgery (100% in the BAV group, 93% in the TAV group,
= 0.044) were included in a systemic follow-up with echocardiography at regular intervals. Among 132 patients, 58 were in the BAV (44%) and 74 in the TAV group (56%). There were no inter-group differences in preoperative patient characteristics, except BAV patients being significantly younger (47 ± 18 y vs. 60 ± 14 y,
< 0.001) and having narrower aortic roots at the level of sinuses (41 ± 6 mm vs. 46 ± 13 mm,
< 0.001) and sinotubular junctions (39 ± 10 mm vs. 42 ± 11,
= 0.032). No perioperative deaths were recorded. At four years, there was no significant difference in terms of overall survival (96.3% BAV vs. 97.2% TAV,
= 0.373), freedom from valve reintervention (85.2% BAV vs. 93.4% TAV,
= 0.905), and freedom from severe aortic regurgitation (94.1% BAV vs. 82.9% TAV,
= 0.222). Surgical repair of BAV combined with extra-aortic annuloplasty can be performed with low perioperative morbidity and mortality and excellent mid-term results which are comparable to TAV repair.
The essential role of immunoglobulin G (IgG) in immune system regulation and combatting infectious diseases cannot be fully recognized without an understanding of the changes in its N-glycans ...attached to the asparagine 297 of the fragment crystallizable (Fc) domain that occur under such circumstances. These glycans impact the antibody stability, half-life, secretion, immunogenicity, and effector functions. Therefore, in this study, we analyzed and compared the total IgG glycome—at the level of individual glycan structures and derived glycosylation traits (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc))—of 64 patients with influenza, 77 patients with coronavirus disease 2019 (COVID-19), and 56 healthy controls. Our study revealed a significant decrease in IgG galactosylation, sialylation, and bisecting GlcNAc (where the latter shows the most significant decrease) in deceased COVID-19 patients, whereas IgG fucosylation was increased. On the other hand, IgG galactosylation remained stable in influenza patients and COVID-19 survivors. IgG glycosylation in influenza patients was more time-dependent: In the first seven days of the disease, sialylation increased and fucosylation and bisecting GlcNAc decreased; in the next 21 days, sialylation decreased and fucosylation increased (while bisecting GlcNAc remained stable). The similarity of IgG glycosylation changes in COVID-19 survivors and influenza patients may be the consequence of an adequate immune response to enveloped viruses, while the observed changes in deceased COVID-19 patients may indicate its deviation.
We cross sectionally evaluated COVID-19 and seasonal flu vaccination rates among 94 dyads consisting of informal caregiver family member and non-institutionalized patient with dementia observed in ...family-medicine practice in Zagreb, Croatia. COVID-19 vaccination rates in caregivers (78.7%) and patients with dementia (82.9%) were significantly higher than in general population. Caregiver and patient COVID-19 vaccination status (CVS) did not correlate. Among caregivers, seasonal flu vaccination (
P
= 0.004) but no other investigated factors related to caregiving or dementia severity showed significant association with CVS. Among patients with dementia, CVS was significantly associated with lower number of caregiver hours dedicated per week (
P
= 0.017), higher caregiver SF-36 role emotional HRQoL (
P
= 0.017), younger patient age (
P
= 0.027), higher MMSE (
P
= 0.030), higher Barthel index (
P
= 0.006), absence of neuropsychiatric symptoms of agitation and aggression (
P
= 0.031), lower overall caregiver burden (
P
= 0.034), lower burden of personal strain
(P
= 0.023) and lower burden of frustration (
P
= 0.016). Caregiving and severity of dementia-related factors significantly affect patient, but not caregiver CVS.
Aims
Heart failure with reduced ejection fraction (HFrEF) poses significant challenges for clinicians and researchers, owing to its multifaceted aetiology and complex treatment regimens. In light of ...this, artificial intelligence methods offer an innovative approach to identifying relationships within complex clinical datasets. Our study aims to explore the potential for machine learning algorithms to provide deeper insights into datasets of HFrEF patients.
Methods
To this end, we analysed a cohort of 386 HFrEF patients who had been initiated on sodium‐glucose co‐transporter‐2 inhibitor treatment and had completed a minimum of a 6‐month follow‐up.
Results
In traditional frequentist statistical analyses, patients receiving the highest doses of beta‐blockers (BBs) (chi‐square test, P = .036) and those newly initiated on sacubitril‐valsartan (chi‐square test, P = .023) showed better outcomes. However, none of these pharmacological features stood out as independent predictors of improved outcomes in the Cox proportional hazards model. In contrast, when employing eXtreme Gradient Boosting (XGBoost) algorithms in conjunction with the data using Shapley additive explanations (SHAP), we identified several models with significant predictive power. The XGBoost algorithm inherently accommodates non‐linear distribution, multicollinearity and confounding. Within this framework, pharmacological categories like ‘newly initiated treatment with sacubitril/valsartan’ and ‘BB dose escalation’ emerged as strong predictors of long‐term outcomes.
Conclusions
In this manuscript, we not only emphasize the strengths of this machine learning approach but also discuss its potential limitations and the risk of identifying statistically significant yet clinically irrelevant predictors.
