bluuebunny/crossref_metadata_2025 huggingface dataset:
Atherosclerotic coronary artery disease prevalence in master athletes exhibiting exercise-induced ventricular arrhythmias: relevance for preparticipation screening
Authors: Graziano F , Millin A , Cozza E , Mattesi G , Motta R , Micchi A , Filippini R , Ciccio' C , Zamboni F , Pergola V , Zorzi A
Published: October 2024

Background

Coronary atherosclerotic disease (CAD) is the leading cause of sudden cardiac death among master athletes (≥35 years). During pre-participation screening (PPS), the primary indication for investigating CAD in these population is ST-segment depression (STD) at exercise test (ET). Additionally, a developing indication involves the identification of high-risk premature ventricular beats (PVBs). Nevertheless, the prevalence of CAD among master athletes displaying PVBs remains uncertain.

Objective

The aim of this study was to evaluate the prevalence of CAD in master athletes who underwent coronary computed tomography (CCT) due to high-risk PVBs during PPS (emerging indication), and to compare this population to age-, gender- and risk factors-matched group of athletes who underwent CCT due to STD during ET (traditional indication).

Methods

We retrospectively enrolled master athletes with no baseline ECG abnormalities and no previous history of heart disease who underwent CCT because of a positive ET during PPS, for PVBs or STD. The entity of the disease was assessed using the CAD-RADs scoring system.

Results

The population resulted to be composed by 130 Caucasian athletes, median age 54 (46.5-60.5 years, 84% male), 74% practiced endurance sports. Eighty-two (63%) of them underwent CCT for STD and 48 (37%) for high-risk PVBs. A CAD-RADs of 0 was detected in 64.3% of athletes, 1-2 in 22.2%, 3 in 6.3%, and 4A-4B in 7.1%. A significant CAD was found in 10.4% of athletes investigated for PVBs at ET, and 14.6% in subjects with STD (p=0.5). Among athletes with moderate-severe CAD, 82.4% had one or more cardiovascular risk factors, while 17.6% had no risk factors (Figure 1).

Conclusions

The prevalence of CAD in master athletes is equivalent in case of PVBs and STD. The severity of CAD increases with an increasing number of cardiovascular risk factors. Therefore, in these cases the number of risk factors is an important variable to consider in the prescription of CCT.Figure 1
Incidence and characteristics of premature ventricular beats in competitive athletes at preparticipation exercise testing
Authors: Pizzolato M , Graziano F , Corrado D , Zorzi A
Published: October 2024

Introduction

The European Society of Cardiology preparticipation screening (PPS) protocol for athletes includes history, physical examination and resting ECG only. However, adding exercise testing (ET) aimed at evaluating ventricular arrhythmias (VAs) inducibility may increase the chances to identify cardiac diseases at-risk of sudden death that would otherwise be missed. Recent studies showed that the risk that premature ventricular beats (PVBs) at ET are associated to an underlying disease depends not just on their number but on characteristics such as morphology and complexity. However, there are no data on the incidence of at-risk PVBs at ET, thus requiring further tests to rule-out a cardiac disease, in apparently healthy athletes.

Aim

To assess the incidence and characteristics of VAs in a cohort of apparently healthy athletes undergoing annual PPS including ET.

Methods

We included a consecutive series of 1431 (24±13 year-old, 75% males) competitive athletes who underwent PPS in 2023. According to the Italian law and national guidelines, PPS must include ET with a different protocol according to age: in athletes younger than 35 years (81% of the study group) a rapid constant-load ET target at evaluating VAs inducibility was performed while in athletes older than 35 years a standard incremental ET was carried out. PVBs recorded during ET were assessed in terms of morphology, complexity and response to exercise.

Results

the incidence of at least 1 PVB was 14.5%, with a statistically significant increase according to age (p<0.001, Figure). If only athletes with frequent (at least 5 isolated PVBs) or complex (at least 1 couplet/triplet/NSVT) VAs are considered, the incidence was 4.3%, still with a significant increase according to age. In particular, among athletes older than 35 years, the incidence of PVBs was 34.1% and of frequent/complex PVBs was 15.2%. As shown in the table and figure, more than half of athletes with PVBs showed at-risk features such as persistence/increase (rather than suppression) of VAs during exercise and an "uncommon" morphology (i.e. different than infundibular or fascicular).

Conclusions

PVBs during ET for preparticipation screening occurred in a sizeable proportion of athletes, particularly in those older than 35 years, and many showed at-risk features such as complexity, uncommon morphologies or exercise-inducibility. Despite VAs at ET may be the only sign of a disease at risk of sudden death, their high incidence may substantially impact on the need for further investigations after PPS. Hence, more efforts should be put to identify which PVBs characteristics are predictive for an underlying cardiac disease, particularly in master athletes.
Synthetic assessment of cardiac autonomic modulation and Baevsky stress index in patients with synucleinopathies
Authors: Brisinda D , Picerni M , Fenici P , Fenici R
Published: October 2024

Background

The Baevsky Stress Index (BSTRi), calculated from Heart Rate Variability (HRV) data, has been proposed for quantitative assessment of physiological stress, with higher scores indicating higher levels of physical and/or psychological stress [1]. Cardiac autonomic modulation can be synthetically quantified by calculating the parasympathetic (PNSi) and the sympathetic (SNSi) indexes. The values of the BSTRi, SNSi, and PNSi in patients with synucleinopathies of different prognoses have not been reported yet.

Purpose

To quantify, in patients with Parkinson's disease (PD) and Multisystem Atrophy (MSA), the BSTRi, its correlation with the PNSi and the SNSi indexes, and their potential value for a synthetic assessment of cardiac autonomic modulation and early differential diagnosis between PD and MSA.

Methods

Holter ECG data of 66 patients with Parkinsonian syndromes were retrospectively analyzed after 10 years of follow-up. Out of them, 34 patients with a certain diagnosis of PD (17) and MSA (17) were selected for this study. HRV was analyzed with the Kubios software (version 4.0), providing automatic calculation of the BSTRi, PNSi, and SNSi [2], as well as of time domain (TD), frequency domain (FD), nonlinear (NL), and time-varying (TV) HRV parameters. HRV was calculated from selected short-term intervals (of 5 minutes), during daily activity (ACT5’), and non-REM sleep (NREM5’), and from 24-hours Holter recordings. Patients’ HRV findings were compared with those of 51 age-matched healthy subjects (HS).

Results

An example of individual automatic graphic summary is shown in Figure 1. Both short-term and 24-hour BSTRi and SNSi values were significantly (p < 0.05) higher in PD and MSA compared to those of HS, in all investigated conditions. Short-term PNSi was significantly higher in HS than in PD in all conditions, but only during NREM5’ in MSA patients (Table 1). No significant difference was found between the indexes of PD and MSA patients. As in HS (R=92), BSTRi was positively correlated with the SNSi in MSA (average R= 0.83 and 0.89 during ACT5’ and NREM5’, respectively), but less evident in PD (R=0.67). The inverse correlation between PNSi and SNSi (R=0.75 in HS) was lost in both MSA and PD.

Conclusions

Higher values of BSTRi in PD and MSA compared to HS suggest that patients with synucleinopathies do experience higher levels of psychophysiological stress, which may affect their quality of life negatively. However, since no significant difference was found in this study between BSTRi values of PD and MSA patients, BSTRi seems at present unreliable for early differentiation between the two diseases. Telematic assessment of BSTRi, SNSi, and PNSi could be useful for remote monitoring of PD and MSA patients’ psychophysiological stress, to provide timely intervention and adaptive treatment.Fig.1 Example of graphic summary (ACT5')
Exercise stress echocardiography detects patients with paroxysmal/persistent atrial fibrillation
Authors: Zagatina A , Ciampi Q , Vazquez J P , Begidova I , Padang R , Boshchenko A , Merli E , Rodriguez-Zanella H , Kobal S , Agoston G , Varga A , Wierzbowska-Drabik K , Arbucci R , Pellikka P A , Picano E
Published: October 2024

Background

Atrial fibrillation (AF) is the most prevalent atrial tachyarrhythmia, affecting an estimated 2-4% of adults worldwide. AF is a well-recognized and treatable risk factor for stroke, but it often remains asymptomatic or subclinical, leading to underdiagnosis. This study aimed to identify distinguishing signs during exercise stress echocardiography (ESE) among patients in sinus rhythm (SR), with and without history of paroxysmal/persistent AF (PAF).

Methods

An international prospective cohort comprising 1035 consecutive patients was initially considered from 12 cardiology institutions. These patients were referred for clinically-driven ESE as part of the Stress Echo 2020-2030 study network. All patients underwent comprehensive ESE with the ABCDE protocol, which included assessment of B-lines, left ventricle contractile reserve (LVCR), ECG-based heart rate reserve (HRR), LV ejection fraction (EF), LV end-diastolic volume, E/e’, pulmonary artery systolic pressure estimation, tricuspid annular plane sytolic excursion (TAPSE), left atrium volume index (LAVi) and left atrium reservoir phase strain (LASr) at rest and with exercise.

Results

After excluding 89 patients who were in AF during the ESE, 946 patients in SR were included as the main study cohort (101 with and 845 without a history of PAF). A scoring system was then constructed using all independent variables that differentiate the two groups (those with and without history of PAF). Presence of systemic hypertension, rest LAVI>31ml/m2, rest |LASr|< 21%, stress LAVI >29 ml/m2, stress |LASr| <24%, stress E/e’ >7, ∆TAPSE <4.5 mm, HRR<1.87, and LVCR<1.6 were identified as the discriminators between patients with and without PAF. The composite score, summing all 9 items (with a total score range from 0 to 9), yielded a score of >4 as the best balance between sensitivity (87%) and specificity (60%) in predicting those with PAF. The receiver operating characteristic curve analysis of the scoring model showed an AUC of 0.79 (p-value <0.0001), Figure.

Conclusion

ESE evaluation can be a valuable adjunct for identifying patients in SR with history of PAF. This multifaceted approach enhances the potential for more accurate detection and clinical management of individuals in SR at risk for AF, who could be considered for aggressive monitoring programs to prevent the development of new onset AF and subsequent increase in cardiovascular risk.
Dementia in patients with early cardiovascular complications following ischaemic stroke: A neglected complication of the stroke-heart syndrome
Authors: Bucci T , Choi S E , Tsang C T W , Buckley B J R , Pignatelli P , Scheitz J F , Lip G Y H , Abdul-Rahim A H
Published: October 2024

Background

Early cardiovascular complications may occur in 20-30% of patients following following ischaemic stroke (stroke-heart-syndrome, SHS). The risk of dementia in patients with SHS remains unexplored. We aimed to quantify the risk of incident dementia in patients with SHS.

Methods

We conducted a retrospective analysis using a global federated health care network (TriNetX). We included patients who were discharged alive post-ischaemic stroke from 2000 to 2022. These individuals were classified into two cohorts based on the incidence of cardiovascular complications within 30 days post-stroke (acute heart failure [HF], acute myocardial infarction [AMI], ventricular fibrillation or flutter [VFF], or Takotsubo disease [TTS]), ie. those with SHS (Group 1) and those with stroke-only (without SHS; Group 2). The primary outcome was the five-year risk of dementia (vascular dementia [F01], dementia in other disease [F02], unspecified dementia [F03], Alzheimer’s disease [G30]). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression analysis after 1:1 propensity score matching (PSM).

Results

We identified 70,113 patients with SHS (age 67.3±14.0; 42.2% females) and 1,092,540 patients with stroke-only (age 65.2±14.9, 48.1% females). Prior to PSM, patients with SHS were generally older and had a higher prevalence of cardiovascular treatments compared to those without SHS. Following PSM, 70,111 well-balanced patients were considered in each group, however, patients with SHS had a higher risk of dementia compared to patients with stroke-only (HR 1.25, 95%CI 1.20-1.30).

Among the SHS complications, the highest dementia risks were associated with acute HF (HR 1.28, 95%CI 1.21-1.36) and AMI (HR 1.24, 95%CI 1.17-1.30), with no significant associations were found for TTS, and VFF. The increased risk of dementia in patients with SHS compared to patients with stroke-only was independent of oral anticoagulant (OAC) use, sex, and age (> or < 75 years) [Figure 1].

Conclusion

Stroke-heart syndrome is associated with increased risk of dementia. Innovative strategies to identify and to prevent SHS complications would improve long-term prognosis in patients with recent stroke.
Depression and its impact on stroke risk and mortality in post-percutaneous coronary intervention patients: a nationwide retrospective cohort study
Authors: Lee Y J , Cheon D , Lee J H , Park M S , Choi J H , Lee S J , Han S W , Han K D , Lee M W , Park Y M
Published: October 2024

Background/Introduction

Cardiovascular disease (CVD) remains a leading cause of global mortality, with percutaneous coronary intervention (PCI) being a common therapeutic procedure for managing CVD. While depression is recognized as a risk factor for adverse cardiovascular outcomes post-PCI, its association with stroke risk in this patient group has been less explored.

Purpose

This study aims to evaluate the association between pre-existing depression and the incidence of stroke, alongside other cardiovascular outcomes and mortality, in patients undergoing PCI.

Methods

Utilizing the Korean National Health Insurance Service database, a population-based retrospective cohort study was conducted, encompassing individuals who underwent PCI between 2010 and 2017, with a follow-up until 2019. Depression was identified through ICD-10 codes prior to PCI. The primary outcome was acute stroke incidence, with all-cause mortality and revascularization as secondary outcomes. Adjustments were made for sociodemographic, lifestyle factors, and comorbidities.

Results

Among 164,198 individuals, those with pre-existing depression (17.4% of the cohort) exhibited a 27% increased risk of acute stroke (aHR 1.27, 95% CI 1.20-1.35) and a 25% higher risk of all-cause mortality (aHR 1.25, 95% CI 1.21-1.29) compared to those without. The association was stronger in individuals under 65 years and varied by sex, with males showing a higher risk of mortality.

Conclusion(s)

Pre-existing depression in patients undergoing PCI is associated with a significantly increased risk of stroke and all-cause mortality, particularly in younger patients. These findings highlight the importance of depression management as part of comprehensive care in post-PCI patients, suggesting potential benefits in reducing stroke risk and improving survival outcomes. Further research is warranted to explore the mechanisms and intervention strategies that could mitigate these risks.Study FlowchartRisk of stroke and all-cause death
Prevalence of Brugada ECG pattern in psychiatric patients: a longitudinal prospective cohort of 550 patients
Authors: Margaglione A , Santoro F , Leccisotti I , Ragnatela I , D'alessandro D , Niglio F , Bellomo A , Altamura M , Brunetti N D
Published: October 2024

Background

Brugada syndrome (BrS) is an inherited disorder with autosomal dominant transmission, which occurs predominantly in males in the third to fourth decade of life with resting syncope, nocturnal agonic breathing, major ventricular arrhythmias and sudden death. Arrhythmic complications can occur spontaneously or following exposure to triggers such as fever, or certain categories of medications, including psychiatric drugs.

Aim of the study

To evaluate the prevalence of Brugada ECG pattern in psychiatric patients.

Methods

from January 2023 to Decembre 2023, 550 consecutive patients who were admitted to the psychiatric department of our university hospital were enrolled. For each patient, electrocardiographic and anamnestic data including psychiatric diagnosis, current drug therapy and family history were collected.

Results

Twenty-one out of five-hundred and fifty patients (3.8%) presented with a Brugada ECG pattern. Mean age was 42±6 years and seventeen out of twenty-one patients (81%) were male.

Two patients exhibited a Spontaneous type 1 Brugada ECG pattern meanwhile nineteen patients had a Brugada type 2 or 3 ECG pattern. When compared to the general population, those with Brugada ECG had longer P wave duration (110±7 vs 103±13 msec p<0.01) and longer QRS duration (97±14 vs 89±12 msec p=0.04).

Evaluating psychiatric disorders, patients with Brugada ECG had high prevalence of mood disorders (10 out of 21, 47%). Other disorders were schizophrenia (3 out of 21, 14%), cognitive retardation (5 out of 21, 23%), and attention disorder (1 out of 21, 5%). Moreover 4 patients were drug addicted. Only 5 out of 21 (24%) patients had a family history of psychiatric and neurological disorders.

Conclusions

Brugada ECG pattern has a prevalence of 3.8% in a large cohort of psychiatric patients. Mood disorders was the most common diagnosis in this cohort. Large prospective registries are needed to evaluate the clinical feature and potential clinical implication of this findings.
Anti-Apolipoprotein A-1 IgG, incident cardiovascular events and lipid paradox in rheumatoid arthritis
Authors: Vuilleumier N , Mongin D , Pagano S , Lamacchia C , Juillard C , Antinori-Malaspina P , Dan D , Ciurea A , Burkhard M , Gabay C , Finckh A
Published: October 2024

Objectives

To validate the prognostic accuracy of anti-apolipoprotein A-1 IgG (AAA1) for incident major adverse cardiovascular (CV) events (MACE) in rheumatoid arthritis (RA) and study their associations with the lipid paradox at a multicentric scale.

Methods

Baseline AAA1 -, lipid profile, atherogenic indexes, and cardiac biomarkers were measured on the serum of 1472 RA patients included in the prospective Swiss Clinical Quality Management registry with a median follow-up duration of 4.4 years. MACE was the primary endpoint defined as CV death, incident fatal or nonfatal stroke, or myocardial infarction (MI), while elective coronary revascularisation (ECR) was the secondary endpoint. Discriminant accuracy, and incidence rate ratios (IRR) were respectively assessed by C-statistics and Poisson regression models.

Results

During follow-up, 2.4% (35/1472) patients experienced MACE, consisting in 6 CV deaths, 11 MI and 18 strokes. ECR occurred in 2.1% (31/1472) of patients. C-statistics indicated that AAA1 had a significant discriminant accuracy for incident MACE (C-statistics: 0.60, 95% confidence intervals [95%CI]: 0.57-0.98, p=0.03), mostly driven by CV deaths (C-statistics:0.77; 95%CI: 0.57-0.98, p=0.01) and without predicting incident ECR. IRR indicated that for every unit increase in AAA1, incident CV death rate increased by 5-fold (95%CI:3.6-7.3), independently of various models’ adjustments. At the predefined and validated cut-off, AAA1 displayed negative predictive values above 97% for the MACE components. AAA1 inversely correlated with total, and HDL cholesterol, but not with atherogenic indexes.

Conclusions

AAA1 independently predict CV deaths in RA. Whether AAA1 could improve CV risk stratification by identifying in particular low CV risk patients remains to be demonstrated.
Cardiac structure and function in people with cystic fibrosis
Authors: Flarup Dons M , Steen Duus L , Faber Thudium R , Dam Nielsen S D N , Olsen M F , Qvist T , Lassen M C H , Skaarup K G , Johansen N D , Bluhme T M S , Katzenstein T L , Pressler T , Faurholt-Jepsen D , Biering-Soerensen T
Published: October 2024

Background

Cystic fibrosis (CF) is an autosomal recessive disease affecting multiple organs, however the extent of cardiac involvement in CF is yet to be determined. The remarkable therapeutic advancements with new highly effective CF transmembrane conductance regulator (CFTR) modulator treatment and subsequent increase in life expectancy substantiates further research.

Purpose

We aimed to explore the prevalence of abnormalities and potential subclinical alterations in cardiac structure and function in adults with CF compared to matched controls and investigate potential cardiovascular risk factors in people with CF (pwCF).

Methods

In this cross-sectional study, 104 adult pwCF in Denmark underwent clinical and echocardiographic examination. All participants were matched 1:1 with controls from the general population on age and sex. Uni- and multivariable linear regression models with adjustment for heart rate, FEV1, smoking status, hypertension and CF-related diabetes (CFRD) were used to test for differences in echocardiographic parameters between cases and controls. Abnormal cardiac function was defined as left ventricular ejection fraction (LVEF) <50%, left ventricular (LV) global longitudinal strain (GLS) < 16% or presence of diastolic dysfunction. Uni- and multivariable logistic regression models adjusted for age, sex, homozygous genotype, FEV1/FVC, BMI, smoking status, CFRD, pancreatic insufficiency, hypertension, and ischemic heart disease were performed to assess associations between potential risk factors and cardiac dysfunction in CF. Forest plots were constructed to visually represent the findings.

Results

Of 104 pwCF, 44% were female, mean age was 34 years, 93% received CFTR modulator treatment, and 91% had mutations with only minimal CFTR function (mutation class I-III). The prevalence of abnormal cardiac function in pwCF was 44% versus 22% in controls. Compared to controls, pwCF were found to have smaller LV dimensions, worse LV diastolic function, and more impaired right ventricle (RV) as well as LV systolic function (Table). After multivariable adjustment, LV diastolic function as well as LV and RV systolic function remained impaired in pwCF as compared to controls. Male sex and decreasing FEV1/FVC ratio remained independently associated with abnormal cardiac function in pwCF (male sex: OR 3.94 (1.56; 9.95), p=0.004 and FEV1/FVC ratio: OR 2.05 per 0.1 unit decrease (1.21; 3.52), p=0.008, respectively) (Figure).

Conclusion

Both left- and right-sided cardiac alterations were found in pwCF. After adjustments for potential risk factors, both RV and LV systolic measures remained altered in pwCF, compared to controls. Male sex and decreasing pulmonary function evaluated by FEV1/FVC-ratio were identified as factors associated with abnormal cardiac function in pwCF.Figure
Early impairment of endothelial and myocardial function in patients with hidradenitis suppurativa
Authors: Ikonomidis I , Pavlidis G , Efthymiou O , Katogiannis K , Diamanti K , Tseneklidou I , Pappa G , Vythoulkas D , Katsanaki E , Vlachomitros D , Vrettou A R , Frogoudaki A , Katoulis A
Published: October 2024

Background/Introduction

Hidradenitis suppurativa (HS) is a chronic, recurrent, debilitating, inflammatory skin disease manifested by painful, deep-seated, inflamed lesions of the apocrine gland-bearing areas of the body (axillae, submammary folds, inguinal and anogenital region). HS has been associated, among others, with an increased cardiovascular risk.

Purpose

We aimed to investigate the endothelial, arterial and left ventricular (LV) myocardial function in patients with severe HS.

Methods

Twenty-eight, not previously treated patients (mean age: 36 ± 13 years) with Hurley stage III disease and a mean score of 19±8 on the International Hidradenitis Suppurativa Severity Score System (IHS4) scale, were studied. Twenty healthy sex-, age- and body mass index -matched individuals, who were also weighted for common cardiovascular risk factors, served as the control group. Both patients and controls were evaluated for: a) perfused boundary region (PBR) of the sublingual microvessels with a diameter of 5-25 μm (an increased PBR value is considered as an indicator of a decrease in thickness of the endothelial glycocalyx), using a dedicated camera (Microscan, GlycoCheck), b) carotid-femoral pulse wave velocity (PWV-Complior), c) flow-mediated dilation (FMD) of the brachial artery and d) LV global longitudinal strain (GLS) using the speckle-tracking echocardiography.

Results

Compared to healthy controls, HS patients had increased PBR value (2.32 ± 0.19 vs. 1.99 ± 0.14 μm, p < 0.001) and decreased FMD (5.7 ± 2.9 vs. 10.3 ± 1.9 %, p < 0.001) and GLS values (-18.6 ± 2.8 vs. -22.5 ± 2.3 %, p < 0.001). In contrast, similar PWV values (9.2 ± 2 vs. 9.1 ± 1.9 m/s, p = 0.937) were recorded between patients and controls (Table). Increased IHS4 score (more severe disease) was associated with increased PBR values (r = 0.42, p = 0.026) and decreased FMD values (r = -0.37, p = 0.045).

Conclusion

Patients with HS show early impairment of endothelial and LV myocardial function, which correlates with the severity of the underlying systemic inflammation.Table
The potential effects of methotrexate on cardiovascular outcomes in rheumatoid arthritis patients: a multi-institutional analysis
Authors: Cervantes M , Miles B , Sills M
Published: October 2024

Introduction and Purpose

The association between rheumatoid arthritis (RA) and increased risk of developing cardiovascular disease has been previously described. Recent studies have also shown that methotrexate may reduce the risk of cardiovascular events in patients with RA but have been limited by small sample size and/or demographic constraints. Methotrexate is a first-line drug treatment for RA and works by suppressing multiple anti-inflammatory and immune reactions, thereby reducing the inflammation that promotes progression of cardiovascular disease in these patients. The goal of this study is to evaluate the potential benefit of methotrexate use on cardiovascular outcomes in patients with RA on a larger scale by utilizing a large international medical record database.

Methods

The TriNetX Diamond network was used for this study. Two cohorts were generated for comparison by using International Classification of Disease 10 (ICD-10) codes. Both cohorts included adult patients with a diagnosis of rheumatoid arthritis (M06) and both were excluded from being treated with the following biologic therapies: etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol. One cohort was on active treatment with methotrexate while the other was excluded from being on it. The cohorts were then balanced for age, gender, race, ethnicity, presence of known coronary artery disease (I20-I25) and history of prior cardiovascular diseases (Z86.7) by propensity score matching and use of the greedy nearest neighbor algorithm. This resulted in 471,054 patients in each arm. They were then compared for the outcomes of acute myocardial infarction, chronic ischemic heart disease, congestive heart failure, and death at 5 years.

Results

Untreated RA patients were 11% more likely to develop myocardial infarction (RR 1.11, 95% CI (1.09,1.14), P value <0.0001) and 14% more likely to develop chronic ischemic heart disease (RR 1.14, 95% CI (1.13,1.15), P value <0.0001). CHF incidence was 21% higher (RR 1.21, 95% CI (1.19,1.22), P value <0.0001) in the untreated group, but 5-year mortality in the two groups was comparable at around 8.2% (RR 0.98, 95% CI (0.97,0.997), P value 0.016).

Conclusion

This study confirms that methotrexate is associated with fewer cardiovascular events in RA patients, especially congestive heart failure. Although the use of methotrexate in patients with RA did not result in a mortality benefit, treatment may offer substantial improvements in patient morbidity and healthcare system cost. These benefits were seen in a sample of greater than 900,000 patients representing every adult demographic. These data reaffirm the previously described association between RA and cardiovascular disease and support the initiation of treatment with methotrexate for any adult patient with RA. Watchful waiting is associated with a higher incidence of adverse events in this population.
Lower modified rodnan skin score values and complement 4 levels are associated with arterial endothelial dysfunction in patients with systemic sclerosis
Authors: Agbuga O D , Caglayan C E , Akray A , Dogan O , Tan Z , Arslan D
Published: October 2024

Background

Systemic sclerosis (SSc) is a multisystem autoimmune disease affecting skin and multiple organs. Although immunopathological evidence supports direct arterial involvement leading to tissue ischemia in SSc, factors associated with arterial involvement are not precisely determined due to the rarity of SSc. In this study, we aimed to investigate aortic stiffness and endothelial functions in patients with SSc.

Methods

Patients under treatment of our Rheumatology department and healthy controls have been included in our study. Aortic stiffness was examined by pulse wave velocity (PWV) exam and endothelial functions were assessed by flow mediated dilation (FMD). Individuals with known atherosclerotic risk factors were excluded from our study. A thorough biochemical examination of all individuals and immunologic markers of patients with SSc was completed. All of the organ involvements in patients with SSc were noted and modified Rodnan skin score (MRSS) was calculated.

Results

A total of 61 patients and 75 healthy controls were included in our study. Brachial-ankle PWV values were significantly higher (6.89±0.93 vs 6.49±0.22 m/sec; p:0.001) and brachial FMD values were significantly lower (16.7±6.7 % vs 18.7±3.8 %; p: 0.03) in patients with SSc. We have also grouped individuals according to severe FMD impairment (FMD < 10%). None of the healthy controls had severe impairment whereas 15 patients with SSc had FMD values lower than 10%. Higher anti-smooth muscle (Sm) antibody positiveness (40 % vs 15.4 %), lower complement 4 levels (23.6±16.7 vs 31.1±11.1 mg/dL), higher plasma iron values (70.3±43.6 vs 31.4±45.2 mcg/dL) and lower MRSS values (11.4±4.8 vs 20.7±10.9) were observed in SSc patients with severe FMD impairment. When we have put these variables in multivariate logistic regression analysis (backward elimination model), we have found an independent association of complement 4 levels (OR: 0.03, [95 % CI: 0.01-0.491], p:0.04) and MRSS values (OR: 0.853, [95 % CI: 0.761-0.955], p:0.006) with significant FMD impairment in patients with SSc.

Conclusion

Arterial stiffness is significantly increased and endothelial functions, as assessed by FMD is significantly decreased in patients with SSc, when compared to healthy controls. Lower complement 4 levels and lower modified Rodnan skin scores seem to be independently associated with significant severe FMD impairment. Although our study included a remarkable amount of patients with SSc, an infrequent autoimmune disease, number of patients included in our study is not adequate to make more precise comments. Further prospective studies with higher amount of patients are required for certain results.
Pulmonary artery thrombosis in Behcet's syndrome: a case series
Authors: Chadli S , Khibri H , Maamar M , Moatassim N , Ammouri W , Harmouche H , Adnaoui M , Tazi Mezalek Z
Published: October 2024

Background

Behçet's syndrome (BS) is a complex multisystemic vasculitis that affects vessels of all sizes and kinds, with a high tendency towards thrombosis. Arterial disease is rare and manifests primarily in the form of pulmonary artery aneurysms (PAA), but also of pulmonary artery thrombosis (PAT) in 1/3 of the cases.

Purpose

Our work aims to depict the profile and outcomes of BS patients presenting with PAT.

Methods

This retrospective, descriptive, and monocentric study was conducted between 2000 and 2022, among 531 adult patients diagnosed with BS (ISG and/or ICBD criteria). All cases of documented PAT were included.

Results

16 cases of PAT were recorded (3%). The mean age of the patients was 34 ± 6 years (19-58), and the sex ratio (M/F) was 4.7:1. Cardiovascular risk factors were mainly active smoking (12%) and high blood pressure (6%). PAT was the revealing manifestation of BS (30%), or occurred after a median of 4.5 years following BS onset. Patients were mostly asymptomatic (69%), or presented with dyspnea (35%), hemoptysis (31%), and thoracic pain (25%). On chest CTA, PAT was often bilateral (78%) and proximal (46%). PAA were frequently observed (25%), being consistently bilateral, multiple, proximal and distal at the same time. Deep venous thrombosis was found in the lower extremities (19%), superior vena cava (27%), and inferior vena cava (6%). Cardiac involvement was also commonly associated (40%), mostly consisting of right intracardiac thrombosis (37%). Concomitant extracardiovascular involvements included mucocutaneous (87%), ocular (26%), articular (25%), and digestive (6%) lesions. Inflammatory parameters were raised in most patients (80%). Hemostasis parameters were within normal ranges and screening for inherited and acquired thrombophilia was negative in all cases. Patients were treated with colchicine (97%), glucocorticoids (93%), cyclophosphamide (47%), azathioprine (47%), and a TNF-a-inhibitor (6%). Curative anticoagulation with low-molecular-weight heparin followed by oral antivitamin K was often prescribed (60%). No surgery or endovascular procedure was performed. Relapse and death were recorded in respectively 15% and 26% of the cases.

Conclusion

In contrast to common thrombotic diseases, PAT in BS is attributed to vasculitis rather than hypercoagulability, resulting in distinct clinical features. The diagnosis should be promptly considered in young men who present with concurrent thrombotic lesions and PAA. Early and appropriate management is imperative to enhance patient outcomes.Left proximal PAT in a BS patient
Out-of-hospital cardiac arrest in patients with psoriasis
Authors: El-Chouli M , Barcella C A , Mohr G H , Mudalige N , Folke F , Torp-Pedersen C , Bruun N E , Lindhardsen J , Ahlehoff O , Gislason G , Skov L , Eroglu T
Published: October 2024

Background

Psoriasis is a complex autoinflammatory disease that has been associated with atherosclerosis, higher risks of cardiovascular diseases, and electrocardiographic changes. Whether these risk factors lead to higher risks of out-of-hospital cardiac arrest (OHCA) is undetermined.

Purpose

To investigate whether psoriasis is associated with OHCA.

Method

Using the nationwide Danish Cardiac Arrest Registry, we identified adult (≥18 years) OHCA patients of presumed cardiac cause with and without psoriasis between June 1st 2001 and December 31st 2019. The association of cardiac arrest was estimated using time-varying Cox regression fitted with a nested case-control design where we matched up to five controls per case on age, sex and year of OHCA and 4 comorbidities: ischemic heart disease, congestive heart failure, cardiovascular risk factors, and major extra cardiac organ disease. In subgroup analyses, the main analysis was repeated in patients with severe psoriasis (presence of inpatient hospital contact during the previous year) as compared to mild psoriasis.

Results

We included 43,967 OHCA cases and matched with 219,772 controls from the general population. The median age was 72 years, 68% were male and 26% had ischemic heart disease, 21% had congestive heart failure, 57% had cardiovascular risk factors, and 33% had extra cardiac organ disease (Table 1). We identified 1,145 (2.6%) cases and 4,971 (2.3%) controls who had psoriasis. Compared with cardiac arrest cases without psoriasis, cases with psoriasis had similar age and sex distribution, prevalence of ischemic heart disease, and congestive heart failure, but a higher prevalence of cardiovascular risk factors, major extra cardiac organ disease and Charlson score distribution. Psoriasis was significantly associated with higher hazard ratios of OHCA: HR 1.16 [95% confidence interval: 1.08 - 1.23] (Figure 1). Compared to no psoriasis, having severe psoriasis was significantly associated with higher hazard of OHCA: HR 1.98 [95% confidence interval: 1.10 - 3.61], while mild psoriasis was not (Figure 1).

Conclusion

In this nationwide nested case-control study, psoriasis was significantly associated with increased hazard of out-of-hospital cardiac arrest. Furthermore, the association was only significant with severe psoriasis compared to those without psoriasis, while mild psoriasis was not. This study highlights the importance of examining cardiovascular risk factors and prioritizing prevention of cardiovascular disease in patients with psoriasis.Figure 1Table 1
Ventricular and supraventricular ectopic beats burden is correlated with bone mineral density and osteoporotic fracture risk in postmenopausal females
Authors: Kawinska A , Sewerynek E , Krekora J , Kurpesa M , Kasprzak J D , Wranicz J K
Published: October 2024

Introduction

Patients (pts) with osteoporosis (OP) have an increased 10-year cardiovascular death risk. Low bone mineral density (BMD) observed in OP may be associated with arrhythmic presentation of cardiovascular diseases (CVD). Few studies assessed the relationship between OP and arrhythmia.

Aim

Arrhythmias assessment in pts with OP.

Methods

A total of 103 postmenopausal female pts (mean age 69 +/- 7), consulted by endocrinologist, were divided into 2 groups according to BMD (assessed by dual energy X-ray absorptiometry). BMD measurements, expressed as T-score (T-sc), were taken from the femoral neck (T-sc Neck), entire total hip (T-sc TH) and/or spine (T-sc L2-L4, L1-L4). Arrhythmia was evaluated using 24-hour Holter-ECG monitoring (HM). Major osteoporotic and total hip fracture risks (MOFR and THFR, respectively) were assessed by the FRAX scale. We compared 51 pts with OP (T-sc ≤ -2.5), with 52 matched controls without OP, including 44 pts with osteopenia (T-sc > -2.5). There were no significant differences between the groups regarding the history of stroke, myocardial infarction, coronary artery disease or arterial hypertension. Exclusion criteria included heart failure NYHA >II and/or LVEF <36%, acute coronary syndrome within the last 6 months, severe valvular disease, cardiac implantable electronic device.

Results

There was a trend towards a greater number of supraventricular and ventricular arrhythmias in the OP group compared to the controls. Arrhythmic burden was significantly correlated with BMD measures: correlations were observed between 24-hour ventricular ectopic beats (VEB) count with T-sc Neck (r=-0.20, p=0.04), with T-sc TH (r=-0.22, p=0.03). The number of supraventricular ectopic beats (SVEB) in HM was also correlated with BMD parameters: T-sc Neck (r=-0.21, p=0.03), T-sc TH (r=-0.23, p=0.02). Multivariate analysis (linear regression model) revealed that age and T-sc TH were independently related with ectopy: age (0.07; CI: 0.01 - 0.13, p=0.03) and T-sc TH (-0.58; CI: -1.07 - -0.08, p=0.02) were predictors for VEB, and SVEB were related to age (0.07; CI: 0.03 - 0.12, p<0.01) and, with borderline significance with T-sc TH (-0.34; CI: -0.699 - 0.012, p=0.058). Ectopic beats count was also positively correlated with osteoporotic fracture risk: VEB with THFR (r=0.206, p=0.04) and SVEB with MOFR (r=0.21, p=0.04).

Conclusions

The study showed an increased arrhythmia burden as detected in HM in pts with OP. Beside the T-sc TH, age was identified as an independent factor of increased SVEB / VEB. The main significant negative correlations were observed between the number of VEB / SVEB and BMD in femur (T-sc Neck, T-sc TH). Ectopic beats count was also positively correlated with osteoporotic fracture risk: VEB with THFR and SVEB with MOFR.
Influence of persistent atrial fibrillation on the prognosis of heart failure with preserved, mildly reduced, and reduced ejection fraction in women and men
Authors: Mansur A , Del Carlo C H , Avakian S D , Nascimento G B , Machado G S , Pereira-Barreto A C
Published: October 2024

Introduction

Heart failure (HF) is one of the leading causes of death from cardiovascular disease. Persistent atrial fibrillation (PAF) is associated with a worse prognosis in HF. However, little is known about the influence of AF on mortality in women and men with heart failure with preserved (HFpEF ≥50%), mildly reduced (HFmrEF 41% to 49%), and reduced ejection fraction (HFrEF ≤40%).

Purpose

to analyze the characteristics and influence of PAF on the prognosis of different HF phenotypes.

Methods

From February 2017 to September 2020, we analyzed hospitalizations, emergency admissions, and mortality of different HF phenotypes with and without PAF. Baseline data included clinical features and echocardiographic findings. Statistical analyses were performed using the Kaplan-Meier (K-M) and Cox proportional hazards methods to analyze mortality rates.

Results

We studied 11,543 patients, with a mean of 64.1±14.0 years: 55.1% male, 42% with HFrEF, 12.8% with HFmrEF, and 45.1% with HFpEF. PAF was associated with higher mean age (67.6±14.3 vs. 62.8±13.4 years, p<0.001) and more prevalent in men (21% vs. 19%; p=0.019) and in patients with valvular and Chagas etiologies, chronic kidney disease (CKD), stroke, and anemia. The prevalence of PAF in women and men was, respectively, 12.4% vs. 18.3% (p<0.001) in HFrEF, 18.1% vs. 22.2% (p=0.029) in HFmrEF, and 23.3% vs. 23.9 (p=NS) in HFpEF. The overall mortality was 21.6%, with mortality being 2.4 times higher in patients with PAF (40.9% vs. 16.7%, p<0.001) compared to sinus rhythm but similar in women and men with PAF (39.5% vs. 41.9%; p=NS), respectively. The hospitalization (30.3% vs 19.4%, p<0.001) and emergency admissions (38.4% vs 25.7%, p<0.001) were higher in patients with AF. Cumulative mortality was higher in patients with PAF in all HF phenotypes: HFrEF (36.6%), HFmrEF (16.8%), HFpEF (46.6%; p<0.001). Men had higher cumulative mortality in HFrEF (18.3% vs. 12.4%; p<0.001) and in HFmrEF (22.2% vs. 18.09%; p=0.029), but not for HFpEF (23.9% vs. 23.3%; p=NS). In the multivariate analysis, adjusted for age, sex, previous myocardial infarction and stroke, diabetes, CKD, PAF, Cardiac surgery, and electronic device implantation, PAF was an independent predictor of death in all HF phenotypes: HFrEF [HR=1.78(95%CI:1.57-2.02); p<0.001], HFmrEF [HR=2.14(95%CI:1.74-2.65); p<0.001], HFpEF [HR=2.08(95%CI:1.82-2.37); p<0.001].

Conclusion

PAF is a frequent comorbidity in HF and is associated with a worse prognosis in all HF phenotypes. Women with PAF had a better prognosis than men with AF in HFrEF and HFmrEF. Sex-specific strategies to maintain sinus rhythm in HF patients on the overall risk of death are needed.
Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography
Authors: Kwiecinski J , Wang K L , Tzolos E , Moss A , Daghem M , Dey D , Williams M C , Slomka P , Dweck M R , Newby D E
Published: October 2024

Background

There are sex differences in the extent, severity, and outcomes of coronary artery disease.

Purpose

To assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men.

Methods

In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men.

Results

Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p=0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p=0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p=0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n=80) and 48.3% (n=73); p=0.42), or CMA values >1.56 (21.8% (n=33) and 21.8% (n=33); p=1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n=10) and 7.8% of men (n=66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p=0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p<0.001).

Conclusions

Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.Sex differences in CAD activityCase examples
Evaluation of coronary microvascular dysfunction and vasospasm in patients with angina and non-obstructive coronary artery disease
Authors: Ashokprabhu N , Kaur S , Tzoumas A , Schmidt C , Roca Alvarez Y , Fox J , Tapp D , Hamstra M , Henry T , Quesada O
Published: October 2024

Background

Angina in the absence of obstructive coronary artery disease (CAD) is a growing cause of morbidity and mortality, exceeding the economic burden of CAD. Roughly 50-70% of patients undergoing invasive angiography for anginal symptoms have non-obstructive CAD. Within this category, there are distinct sub-populations including patients with angina without evidence of ischemia on prior stress testing (ANOCA), evidence of ischemia on stress testing (INOCA), or history of obstructive CAD with prior revascularization (ANOCA-HxCAD). Coronary microvascular dysfunction (CMD) and/or epicardial vasospasm are common causes of angina in the absence of epicardial CAD despite optimal medical therapy. Differences between these groups, in terms of risk factors and diagnoses remain relatively unknown.

Purpose

To compare clinical characteristics, symptoms, and diagnoses between patients with ANOCA, INOCA, and ANOCA-HxCAD.

Methods

In a prospective registry-based cohort study of 306 patients without obstructive CAD (<50% stenosis in epicardial artery) undergoing coronary functional angiography (CFA), we assessed differences in clinical characteristics, symptoms, and CFA diagnoses: (1) endothelial-independent CMD (coronary flow reserve [CFR] <2.5) to adenosine testing, (2) endothelial-dependent CMD (coronary blood flow [CBF]<50% or no change in vessel diameter to 54 mcg intracoronary acetylcholine [ACH]), (3) epicardial vasospasm to 108 mcg intracoronary ACH in 3 groups of patients (ANOCA, INOCA, and ANOCA-HxCAD).

Results

Among the 306 patients undergoing CFA, 89% were female with a median age of 58 years (49, 67). Patients with ANOCA-HxCAD had a significantly higher prevalence of hypertension, diabetes, heart failure with preserved ejection fraction, and experienced worse dyspnea on exertion as measured by University of San Diego Shortness of Breath (UCSD SOB) in comparison to ANOCA or INOCA patients. However, there were no differences between the groups in terms of anginal severity, functional capacity, or quality of life. In terms of CFA diagnoses, vasospasm was more prevalent in ANOCA-HxCAD (p<0.001) and CMD was more prevalent in ANOCA and INOCA patients (p=0.034) (Table 1).

Conclusions

Despite differences in clinical characteristics, patients without obstructive CAD have similar anginal severity, functional capacity, and quality of life regardless of evidence of ischemia on prior stress imaging or history of revascularization. There are differences in CFA diagnoses with higher prevalence of CMD in ANOCA and INOCA patients and higher prevalence of vasospasm in ANOCA-HxCAD patients. Determining the underlying diagnoses changes clinical management; therefore, CFA should be considered in all patients without obstructive CAD.