bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of chronic dietary nitrate on downstream atherogenic metabolites and the enteral microbiome
Authors: Messiha D , Rinke M , Schultz Moreira Amos A , Tratnik A , Hendgen-Cotta U B , Lortz J , Hogrebe K , Kehrmann J , Buer J , Rassaf T , Rammos C 
Published: October 2024

Abstract

Background
Inorganic nitrate, which is abundant in leefy green vegetables and mediates cardioprotective effects through nitric oxide related pathways. The enteral microbiome is an emerging key player in cardiovascular diseases and depends on dietary habits. Whether dietary inorganic nitrate influences atherosclerosis-associated microbiome dependent metabolites like short chain fatty acids (SCFA) and trimethylamine N-oxide (TMAO) has not been elucidated so far.

Purpose
Aim of this study was to investigate the influence of dietary anorganic nitrate intake on atherosclerosis-associated metabolites and the enteral microbiome composition in a healthy trial cohort.

Methods
In this double-blind randomized controlled trial, we included 30 healthy volunteers, who either received dietary nitrate (0,12 mmol/kg bodyweight) or placebo (equimolar amounts of sodium nitrate) for 30 days. The microbiome metabolites TMAO and SCFA were analysed. Furthermore, upstream enteral microbiome composition was analysed by 16S-rRNA sequencing at baseline and follow-up.

Results
Systolic blood pressure significantly decreased after nitrate supplementation (baseline 124,73 mmHg vs follow up 120 mmHg, p &lt; 0.05) with no change in controls. Dietary nitrate supplementation significantly increased TMAO levels (control follow-up 343,88 µg/L vs nitrate follow-up 481,15 µg/L, p &lt; 0.05), while SCFA levels remained unchanged. Mechanistically a change in enteral microbiome composition after dietary nitrate supplementation with decreased abundance of the gram-negative bacteria Akkermansia muciniphila was detected, while overall Shannon diversity, richness and evenness did not differ.

Conclusions
In conclusion, our results indicate that dietary nitrate supplementation alters the enteral microbiome with impact on proatherogenic metabolites. Further work is warranted to investigate the causal relationship between dietary nitrate, the microbiome, downstream metabolites, and the clinical relevance of those findings in a cardiovascular diseased cohort.
The clinical impact of cardiac magnetic resonance imaging upon suspected myocardial infarction with non-obstructive coronary artery disease
Authors: Giudicatti L , Telyuk P , Pasupathy S , Gilbert G , Maredia N , Spiro J , Beltrame J , Hillis G , Austin D , Dwivedi G , Rajwani A 
Published: October 2024

Abstract

Background
Cardiac magnetic resonance (CMR) may identify the underlying pathology in myocardial infarction with non-obstructed coronary arteries (MINOCA), however there are scant prospective data evaluating the more important measure of actual change in diagnosis and management consequent to CMR.

Purpose
To evaluate impact of CMR in MINOCA upon diagnosis, diagnostic certainty and management, adjudicated by treating physicians to minimise investigator bias.

Methods
Prospective, multi-center international pre- and post-CMR study of suspected MINOCA. Physician diagnosis, diagnostic certainty and intended management were established by questionnaire before and after CMR. The primary outcome was change in diagnosis or management. Secondary outcomes were change in diagnosis, change in management, change in diagnostic certainty, and number-needed-to-test for de-prescription of dual antiplatelet therapy (DAPT). Potential predictors of impactful CMR were evaluated by multivariable logistic regression analysis.

Results
320 patients referred by 74 clinicians underwent CMR; mean age 55.6 (12.3) years, 48.1% female. CMR was conducted at median 11 days (IQR 6-19) post presentation. CMR led to change in diagnosis or management in 62.8% (95% CI 57.4% - 68.2%, p&lt;0.0001) and significantly increased diagnostic certainty [8/10 post-CMR (5-9) vs 6/10 pre-CMR (4-7), p&lt;0.0001]. Predictors of impactful CMR on multivariable analysis were early CMR (≤14 days), absence of atheroma on coronary angiography, significant pre-CMR diagnostic uncertainty (≤5/10), and a history of vascular disease. DAPT was deprescribed or modified to single antiplatelet in 61.7% patients. The number-needed-to-test to deprescribe DAPT was 2.6 (and 1.6 if a myocardial infarction mimic was co-suspected pre-CMR), which has important cost-benefit implications for CMR in MINOCA.

Conclusions
In this first prospective multi-centre study of CMR in MINOCA where diagnostic utility was adjudicated by the treating physicians, CMR was associated with frequent and significant changes in diagnosis, clinician certainty and clinical care, including frequent de-prescription of DAPT. Early CMR is to be encouraged, particularly in patients where there is significant diagnostic uncertainty and no atheroma on coronary angiography.
Impact of addressing modifiable risk factors on the 10-year risk of cardiovascular disease in individuals with familial hypercholesterolemia: a causal analysis utilising UK biobank
Authors: Stevens C , Vallejo-Vaz A J , Sharabiani M T A , Brandts J , Barkas F , Elshorbagy A , Mahani A , Ray K K 
Published: October 2024

Abstract

Background
Familial hypercholesterolemia (FH) is a prevalent autosomal dominant disorder characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels from birth. These elevated LDL-C levels significantly amplify the lifetime risk of cardiovascular disease (CVD). While the impact of early and effective initiation of lipid-lowering medication (LLM) on CVD risk is well documented in genetically confirmed FH, the additional impact of addressing modifiable lifestyle risk factors (MLRF) in that patient population remains largely unquantified.

Methods
This study quantified the potential effects of successfully managing 4 MLRF (smoking, obesity, alcohol consumption, and low physical activity) on the 10-year incidence of a first CVD diagnosis in adults with genetically confirmed FH treated with LLM within the UK Biobank. The synthesised causal estimates of these 4 MLF were obtained using two recent causal analysis frameworks, namely the doWhy causal calculus framework and the Causal Forest Double Machine Learning Method.

Results
In 660 FH individuals (mean age 56±8 years; 60.15% women), smoking cessation and reducing body mass index below 30 kg/m2 delivered the most substantial risk reductions (pooled estimates, adjusted for the 3 other MLRF: -6.5% and -3.2%, respectively; both p&lt;0.001), followed by initiating moderate or high physical activity (-1.7%; p&lt;0.001; Figure). Notably, cessation of alcohol consumption significantly increased CVD risk (+2.5%; p&lt;0.001), aligning with existing literature.

Conclusion
In over 10 years, reductions in CVD risk ranging from 1.7% to 6.5% were achievable through smoking cessation, BMI reduction, and enhanced physical activity in FH individuals. Leveraging causal inference methodologies facilitates the discernment of which risk factors offer the most pronounced additional benefits beyond lipid-lowering interventions in this high-risk population.Forest Plot of Causal Effect Estimates
Comparison of Lp(a) assessment in patients with atherosclerotic cardiovascular disease between office-based cardiologists and general practitioners
Authors: Weingaertner O , Glueck S , Werdan K , Schorr J , Beier L , De La Llave A , Barth S D , Von Vultee C , Haerer W 
Published: October 2024

Abstract

Background
Elevated lipoprotein(a) (Lp(a)) levels are a major risk factor that contribute to the development of ASCVD. Different guidelines for the treatment of patients with hypercholesterolemia are available in Germany. The German Cardiac Society recognized the 2019 ESC/EAS guideline for the management of dyslipidemia and endorses the measurement of Lp(a) at least once in a lifetime to identify those with very high inherited Lp(a) levels &gt;180 mg/dL (&gt;430 nmol/L) . The Nationale Versorgungsleitlinie, however, does not recommend testing of Lp(a).

Methods and Objectives
LipidSnapshot is a joint research project consisting of two parts. Part 1 is a prospective, non-interventional multicenter research project at office-based cardiologists (OBCs). Data from 1500 adults with known coronary artery disease, peripheral artery disease, prior myocardial infarction and/or ischemic stroke are collected from selected 49 OBCs. The second part is a retrospective, aggregated analysis of anonymous electronic medical records of 82.375 adult outpatient ASCVD patients documented by general practices (GPs) obtained from the IQVIA Disease Analyzer (note: 54% do not provide information on Lp(a) data to IQVIA). Availability of Lp(a) tests and lipid-lowering therapies (LLTs) in ASCVD patients with available LDL-C values within a 12-month period (July 2022-June 2023) were assessed. One of the objectives of LipidSnapshot is to compare the proportion of Lp(a) assessments in ASCVD patients documented by OBCs and GPs and to evaluate gender-, age- and LLTs-related differences in Lp(a) availability in patients documented by OBCs compared to GPs.

Results
Patients treated by OBCs were on average 72.4 (standard deviation (SD) 10.0) years old and 75.8 % were male while patients in the IQVIA dataset were on average 73.0 (SD 13.2) years old and 60.5% were male. The age distribution was comparable between both specialties. OBCs documented Lp(a) in 20.3% of their ASCVD patients, while only 3.0% of ASCVD patients documented by GPs had Lp(a) values documented. The testing rates in male and female patients were comparable between both specialties (OBC: 19.5 vs. 22.9%; GPs: 3.4 vs. 2.5%). For both specialties, Lp(a) testing rate was higher in younger patients compared to older patients (Table 1) and in patients treated with PCSK9-inhibitors (monoclonal antibodies, inclisiran), either as monotherapy or in combination with statins and/or other LLTs (ezetimibe, bempedoic acid, bile acid sequestrants) (Table 2).

Conclusion
The first snapshot revealed differences in healthcare provision of GPs compared to selected OBCs with lower rates of identification of higher risk patients treated by GPs in Germany.Age-related differences in Lp(a)LLT-related differences in Lp(a)
Cardiac MRI traits linked to cardiomyopathy mutations in phenotype naive carriers
Authors: Croon P M , Vugt M , Allaart C P , Asselbergs F W , Ruijsink B , Winter M M , Schmidt A F 
Published: October 2024

Abstract
Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are prevalent forms of cardiomyopathies, characterised by changes in cardiac structure and function, associated with an increased risk of atrial fibrillation (AF), heart failure (HF), and sudden cardiac death (SCD). Due to these potential life-threatening consequences close monitoring of genetic mutation carriers of HCM and DCM, is important. However, disease onset in these subjects is highly variable, with a substantial subset of people only developing disease late-in-life, or not at all, making risk stratification challenging.
We set out to identify cardiac MRI (CMR) based imaging biomarkers of HCM and DCM carriership in phenotype naïve individuals, which were benchmarked against associations with AF and HF.
CMR and whole genome sequencing (n: 42,723) data were sourced from a UK biobank sample free of heart failure at the time of CMR measurements. A previously validated deep learning(DL) network was used to derive 22 CMR traits(1). Adjusted cox regression models were used to determine the CMR associations with the onset of heart failure and atrial fibrillation, providing empirical validation of the DL CMR network. Univariable and multivariable generalised linear models were employed to identify associations with genetic carriership conditional on cardiac risk factors.
14 and 19 CMR measurements were associated with the time until HF (274 cases), AF (704 cases), respectively. These variables included left-ventricle (LV) ejection fraction (EF), LV end systolic volume (ESV), Right-ventricular (RV) EF and right atrial (RA) EF. Using WGS data we identified 154 people with an HCM mutation and 220 with a DCM mutation, where HCM carriership associated with five and DCM with four CMR traits. This included RA-EF (OR 1.26 95%CI 1.10; 1.45), and RV-EF (OR 1.41 95%CI 1.23;1,63) for HCM, and LV-EF (OR 0.72 95%CI 0.62; 0.84), and RV stroke volume (OR 0.75 95CI 0.62; 0.91) for DCM.
By combining deep learning of CMR with large sample size WGS we were able to identify cardiac imaging biomarkers of HCM and DCM carriership in apparently healthy subjects. This could prove relevant for early identification and monitoring of phenotype naïve people.
Redefining genotype-phenotype correlation among patients with arrhythmogenic cardiomyopathy: a CMR cohort study
Authors: La Vecchia G , Bisaccia G , Perotto M , Leo I , Procopio M C , Licordari R , Miaris N , Wong J , Pantazis A , Bucciarelli-Ducci C 
Published: October 2024

Abstract

Background and purpose
Arrhythmogenic cardiomyopathy (ACM) is a poorly defined, life-threatening condition. We aimed at identifying the patterns of regional wall motion abnormalities, fibrosis, and fatty infiltration seen on Cardiac Magnetic Resonance (CMR) and correlate them with the different genetic backgrounds.

Methods
We retrospectively identified ACM patients who underwent CMR and genetic test analysis. We collected data on CMR-derived cardiac volumes, function and tissue characterization.

Results
Seventy-eight patients with a clinical diagnosis of ACM were enrolled. Genetic tests were performed in 65 (83%) and identified a pathogenetic/likely pathogenetic variant in 51 (78%) patients (38% plakophilin-2, 23% desmoplakin, 5% desmoglein, 5% desmocollin and 8% filamin-C). Imaging features varied according to the genetic background, with subepicardial or mid-wall fibrosis distribution affecting predominantly the lateral and inferior segments of the left ventricle (LV) among the different groups and the septal segments in patients with the filamin-C variant. A characteristic LV subepicardial circumferential LGE pattern ("ring-like") was distinctively and almost exclusively associated with the desmoplakin variant.

Conclusions
Genetic variants of ACM present some common but also distinctive CMR phenotypes that can help in further characterizing the specific disease signatures associated with different genes. Further studies should investigate the prognostic value of these CMR findings.
AI-enabled cardiac chambers volumetry in coronary calcium scans (AI-CAC) predicts heart failure and outperforms NT-proBNP: The Multi-Ethnic Study of Atherosclerosis
Authors: Naghavi M , Reeves A P , Budoff M J , Li D , Atlas K , Zhang C , Atlas T , Roy S K , Henschke C , Wong N D , Defilippi C , Levy D , Yankelevitz D 
Published: October 2024

Abstract

Introduction
Coronary artery calcium (CAC) scans contain useful information beyond the Agatston CAC score that is not currently reported. We recently reported that artificial intelligence (AI)-enabled cardiac chambers volumetry in CAC scans (AI-CAC) predicted incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis (MESA). In this study, we investigated the performance of AI-CAC for prediction of incident heart failure (HF) and compared it with 10 known clinical risk factors, NT-proBNP, and the Agatston CAC score.

Methods
We applied AI-CAC to 5750 CAC scans of asymptomatic individuals (52% women, White 40%, Black 26%, Hispanic 22% Chinese 12%) free of known cardiovascular disease at the MESA baseline examination (2000-2002). We used the 15-year outcomes data and compared the time-dependent area under the curve (AUC) of AI-CAC versus NT-proBNP, Agatston score, and 10 known clinical risk factors (age, gender, diabetes, current smoking, hypertension medication, systolic and diastolic blood pressure, LDL, HDL, total cholesterol, and hs-CRP) for predicting incident HF over 15 years.

Results
Over 15 years of follow-up, 256 HF events accrued. The AUC for predicting HF with AI-CAC (0.826) was significantly higher than NT-proBNP (0.742) and Agatston score (0.712) (p&lt;.0001), and comparable to clinical risk factors (0.818, p=0.4141). AI-CAC category-free Net Reclassification Index (NRI) significantly improved on clinical risk factors (0.32), NT-proBNP (0.46), and Agatston score (0.71) for HF prediction at 15 years (p&lt;0.0001).

Conclusion
AI-CAC significantly outperformed NT-proBNP and the Agatston CAC score, and significantly improved the AUC and category-free NRI of clinical risk factors for incident HF prediction.
Assessment of experimental circulating biomarkers in volume and pressure overload: insights from a cohort study
Authors: Csengeri D , Engler D , Ohlrogge A , Schofer N , Kalbacher D , Zeller T , Blankenberg S , Kirchhof P , Schnabel R 
Published: October 2024

Abstract

Introduction
Experimental biomarkers including Angiopoietin-2 (ANG2), bone morphogenetic protein 10 (BMP10), fibroblast growth factor 23 (FGF23), and insulin-like growth factor-binding protein 7 (IGFBP7) are hypothesized to reflect cardiac pathophysiological processes that are potentially present in adverse cardiac remodeling in volume or pressure overload. This study aims to elucidate the relationship between these circulating biomarkers and the presence of hemodynamically significant pressure or volume overload and adverse outcomes and compare it to N-terminal pro B-type natriuretic peptide (NT-proBNP).

Methods
We studied the association between the four experimental circulating biomarkers in patients with pressure or volume overload with reference to none/mild valvular disease in N=1302 of an observational outpatient cardiology cohort. The median age was 63.0 (25th/75th quartile 51.5, 71.4) years, 445 (34.2%) were women. Circulating biomarkers were quantified using a novel antibody-based method. Logistic regression models with cox regression plots were employed to assess the association of each biomarker with the severity of valve disease concerning volume or pressure overload, adjusted for age and sex.

Results
In the overall population, elevated levels of ANG2, BMP10, FGF23 and IGFB7 were positively associated with the presence of significant volume overload (ANG2: Odds ratio (OR) 1.26 (95% confidence interval (CI) 1.17-1.35), p&lt;0.001; BMP10: OR 2.57 (CI 1.89-3.48), p&lt;0.001; FGF23: OR 1.51 (CI 1.14-1.20), p=0.004; IGFBP7: OR 1.39 (CI 1.14-1.69), p=0.001, NT-proBNP: OR 1.69 (CI 1.47-1.95), p&lt;0.001). No statistically significant association between circulating biomarkers and pressure overload was observed.
Over a median follow-up of 4 years, 31 (20.1%) participants died in the group of volume overload and 9 (40.9%) individuals in the group of pressure overload. After multivariable-adjustment, elevated levels of BMP 10 showed a borderline association with an increased risk of all-cause mortality in individuals with volume overload compared to none/mild valvular disease: hazard ratio (HR) 1.51 (CI 0.96- 2.38), p=0.075. Higher concentrations of all biomarkers were predictive of all-cause mortality for both individuals with volume overload and those with none/mild valvular disease (ANG2: HR 3.72 (CI 1.67-8.33), p=0.001; BMP10: HR 1.65 (CI 1.20-2.26), p=0.002; FGF23: HR 2.08 (CI 1.65-2.62), p&lt;0.001; IGFBP7: HR 1.55 (CI 1.25-1.91), p&lt;0.001; NT-proBNP: HR 1.72 (CI 1.47-2.00), p&lt;0.001).

Conclusions
This study demonstrates that circulating biomarkers involved in distinct pathophysiological pathways of inflammation, fibrosis and calcification are elevated in patients with hemodynamically significant volume overload. Since they are also related to mortality, their clinical role needs to be explored further, also in context with the routine biomarker NT-proBNP.
Novel cardiovascular magnetic resonance imaging heterogeneity biomarkers to diagnose and predict cardiovascular disease: a UK Biobank CMR strain study
Authors: Hesse K , Khanji M , Aung N , Chahal A , Petersen S 
Published: October 2024

Abstract

Background
Myocardial strain evaluation on cardiovascular magnetic resonance imaging (CMR) shows significant promise to investigate cardiac function in vivo. There is concern that derived global longitudinal strain (GLS) and global circumferential strain (GCS) are less sensitive to early pathological cardiac remodelling, especially when regional. By quantifying contractile variability across the myocardium, the absolute longitudinal and circumferential strain coefficients of variation, |CoVLS| and |CoVCS| may facilitate earlier diagnosis and improved prognostication.

Purpose
We compared experimental heterogeneity biomarkers, |CoVLS| and |CoVCS|, to established global strain markers, GLS and GCS, to discriminate prevalent cardiovascular disease (CVD) and predict major adverse cardiovascular events (MACE).

Methods
Prevalent and incident CVD were defined among 44,955 participants from the UK Biobank (UKBB), who had feature-tracking (FT-CMR) derived strain markers. Prevalent CVD was the sum of established cardiovascular diagnoses at the time of baseline CMR, including hypertension, diabetes, atrial fibrillation, coronary artery disease, stroke and heart failure (HF). Incident CVD was newly identified MACE, including death from any cause, myocardial infarction, HF and stroke. Biomarkers were separately regressed against said endpoints, using ordinal logistic and Cox proportional hazards regression respectively. Statistical adjustment was performed for important baseline co-variables, including age, sex, ethnicity, smoking status, body mass index (BMI), low-density lipoprotein (LDL), left atrial volume, left ventricular mass and ejection fraction.

Results
Overall, 30,289 (67.4%) participants had no prevalent CVD, 10,362 (23.0%) had 1 CVD and 29 (0.06%) had ≥5 CVD. |CoVLS|, GLS, |CoVCS| and GCS were associated with a higher odds of prevalent CVD diagnoses (Figure 1). GLS had the greatest strength of association (OR 1.25, 95% CI 1.20-1.29), followed by |CoVCS| (OR 1.14, 95% CI 1.10-1.17). Over median 2.7 years (Q1-Q3 1.9-4.1 years), 966 (2.1%) participants experienced MACE, including 379 (0.8%) deaths, 263 (0.6%) MI, 246 (0.5%) HF, 237 (0.5%) stroke. |CoVLS|, |CoVCS| and GLS were comparable risk markers for MACE (Figure 2). The largest and smallest effect sizes were in predicting HF and death from any cause respectively.

Conclusion
Subclinical cardiac disease is often patchy, diffuse and regional; measures of heterogeneity may be more sensitive to these early pathological signals. We demonstrated that |CoVLS| and |CoVCS| are comparable to GLS and better than GCS in discriminating prevalent cardiac disease and predicting future cardiovascular events. These findings need to be replicated in other population studies and diseased cohorts.