bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic impact of plasma level of NT-pro BNP in patients with microvascular angina – a report from the international cohort study by COVADIS
Authors: Shimokawa H , Suda A , Takahashi J , Ong P , Ang D , Berry C , Camici P , Crea F , Kaski J , Pepine C , Rimoldi O , Sechtem U , Yasuda S , Beltrame J , Merz C 
Published: October 2022

Abstract

Aims
Although the importance of microvascular angina (MVA) has been emerging, prognostic biomarkers for MVA remain to be developed. We thus aimed to examine whether plasma level of N-terminal prohormone of brain natriuretic peptide (NT-pro BNP) could predict the prognosis of MVA patients.

Methods
In the international prospective cohort study of MVA patients by the Coronary Vasomotor Disorders International Study (COVADIS) group, we evaluated the association between plasma level of NT-pro BNP and the incidence of major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure or unstable angina.

Results
We examined a total of 226 MVA patients (M/F 66/160, 61.9±10.2 [SD] years) with both plasma NT-pro BNP levels and echocardiographic data in the COVADIS study. Plasma NT-pro BNP level was elevated (median 94 pg/ml, IQR 45–190) while mean LVEF (69.2±10.9%) and E/e' (10.7±5.2) were almost normal. During follow-up period of a median of 365 days (IQR 365–482), 29 MACEs occurred. ROC curve analysis identified plasma NT-pro BNP level of 78 pg/ml as the optimal cut-off value. Multivariable logistic regression analysis revealed that plasma NT-pro BNP level ≥78 pg/ml significantly correlated with the incidence of MACE (odds ratio (OR) [95% confidence interval (CI)] 3.11 [1.14–8.49], P=0.03). When divided into 2 groups by NT-pro BNP 78 pg/ml, the Kaplan-Meier survival analysis showed a significantly worse prognosis in the group with NT-pro BNP ≥78 (log lank, P=0.03) (Figure).

Conclusions
These results indicate that plasma NT-pro BNP level is a novel prognostic biomarker for MVA patients.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Japan Heart Foundation
Immuno-inflammatory response in patients after myocardial infarction and involvement in fibrosis in vitro
Authors: Miquelestorena-Standley E , Vinhais Da Silva A V , Monnier M , Chadet S , Lemoine R , Ivanes F , Angoulvant D 
Published: October 2022

Abstract

Background
Pathophysiology of acute myocardial infarction (AMI) has been described in mice and is based on a three-stage model involving temporal modifications of immune cells and fibroblasts. The acute inflammatory phase is followed by a reparative phase and fibrous scar maturation phase. Purinergic signaling, particularly P2Y11 receptor, has been reported to be involved in the regulation of inflammation after ischemia and could be an actor of resolution of inflammation after AMI.

Purpose
The aims of our study were: (1) to characterize the immune and P2Y11R profiles of AMI patients and (2) to analyze interactions between patients' immune cells and cardiac fibroblasts in vitro.

Methods
We collected peripheral blood mononuclear cells (PBMC) of 182 patients at various times (H0, H4, H24, H48, D3, M1, M6, M12) after reperfused ST-segment elevation AMI, and of 30 healthy donors. Expression level of genes involved in tolerogenicity profile of dendritic cells (HMOX1, STAT3, IDO1), in T cell polarization (CD4, FOXP3, TBX21/GATA3) as well as P2RY11 were evaluated by RT-PCR. P2Y11R expression was analyzed using flow cytometry. PBMC and human cardiac fibroblasts (HCF) were co-cultured during one day (5PBMC/1 HCF) and gene level expression (ACTA2/VIM, COL1A1), phenotype (α-SMA/vimentin) and secretory (soluble collagen) profiles were analyzed by RT-PCR, flow cytometry and Sircol assay.

Results
In the first 48 hours after AMI, the expression level of HMOX1 (fold-change = 8.478 at H48, p&lt;0.0001), STAT3 (2.856 at H0, p=0.0027) and CD4 increased (2.451 at H48, p=0.0052); IDO1 (0.2055 at H24, p&lt;0.0001) and TBX21/GATA3 ratio decreased (0.4498 at H48, p=0.0026); FOXP3 did not vary significantly. In the same time, the expression level of P2RY11 increased (2.124 at H0, p=0.0015) as well as protein expression in T cells (median MFI = 845.5 at H0 vs 229.5 for healthy donors, p=0.0375). In vitro, we observed a non-significant increase of ACTA2/VIM ratio in HCF co-cultured with H24, M1, M6 PBMC; of α-SMA/vimentin with H48, M12 PBMC; of COL1A1 with H24, H48, M12 PBMC; and of soluble collagen in coculture supernatant with M1 PBMC.

Conclusion
Our results suggest that P2Y11R could be involved in evolution of immune response after AMI, and that, in the first 2 days, circulating immune cells have a reparative profile and could participate in the transformation of fibroblast into myofibroblasts.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Fondation pour la recherche médicale
Biomarker-based prediction of fatal and non-fatal cardiovascular outcomes in individuals of the general population with and without diabetes mellitus
Authors: Haller P M , Gossling A , Brenner H , Iacoviello L , Kee F , Linneberg A , Thorand B , Salomaa V , Soederberg S , Voelzke H , Sans S , Palmieri L , Veronesi G , Blankenberg S , Westermann D 
Published: October 2022

Abstract

Introduction
Cardiovascular biomarkers may reflect different aspects of cardiovascular disease, including myocardial tissue damage (high-sensitive cardiac troponin [hs-cTn]), hemodynamic stress (N-terminal prohormone of brain natriuretic peptide [NT-proBNP)), or inflammation (high-sensitivity C-reactive protein [hs-CRP]).

Purpose
To determine the risk for fatal and non-fatal cardiovascular events in patients with diabetes mellitus (DM), a high-risk group for cardiovascular complications, after accounting for these biomarkers and to determine the risk associated with these biomarkers.

Methods
Harmonized data of population-based studies from the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomaCaRE) and MOnica Risk, Genetics, Archiving and Monograph (MORGAM) consortia were used to calculate hazard ratios (HRs, 95% confidence intervals [CI] per standard deviation) for these biomarkers adjusted for diabetes, patient characteristics and biomarkers for their association with the primary endpoint of fatal and non-fatal cardiovascular events during a median follow-up of 9.6 years (maximum 28 years). Additionally, a years-of-life-lost analysis was conducted stratified by prevalent diabetes and specific biomarker cut-offs known to be associated with increased risk for events (hs-cTnI &gt;5 ng/L, NTproBNP &gt;125 ng/L, hs-CRP &gt;5mg/L).

Results
We included 95,302 individuals, of whom 6,501 had DM (6.8%). Cox-regression analysis revealed DM to be independently associated with the primary endpoint (2.1 [95% CI 1.9, 2.3], p&lt;0.001) despite adjustment for clinical characteristics and biomarkers. Also, all three biomarkers were independent predictors themselves: log-transformed NT-proBNP 1.3 [95% CI 1.3, 1.4] p&lt;0.001; log-transformed hs-CRP 1.2 [95% CI 1.1, 1.2] p&lt;0.001; third-root-transformed hs-cTnI 1.1 [95% CI 1.0, 1.1] p=0.0038). The sex-, age- and cohort-adjusted HR for the primary endpoint according to absolute biomarker concentrations derived by cox-regression models using cubic splines is provided for the three biomarkers in Figure 1. Upon dichotomization of biomarkers, individuals with diabetes and at least one elevated biomarker lost a median of 15.5 healthy years because of the primary endpoint (Kaplan-Meier plot in Figure 2, with age on the x-axis).

Conclusion
Our findings confirm that diabetes confers a residual cardiovascular risk beyond adjustment for clinical characteristics and cardiovascular biomarker. Furthermore, biomarkers may aid in the identification of patients at highest risk, which should be considered in future models of risk prediction.

Funding Acknowledgement
Type of funding sources: None.
Prediction of all-cause mortality in cardiovascular patients by using machine learning models
Authors: Tsarapatsani K , Pezoulas V , Sakellarios A , Tsakanikas V , Marz W , Kleber M , Michalis L , Fotiadis D 
Published: October 2022

Abstract

Background
Cardiovascular disease (CVD) is the leading cause of death worldwide. The prediction of all-cause death in patients with chronic cardiovascular risk will enable improved preventive strategies.

Purpose
This study aims to predict death of patients, who suffering from cardiovascular disease, within a follow-up period of 20 years. For this purpose was utilized the Ludwigshafen Risk and Cardiovascular Health (LURIC) study was utilized and employed machine learning models.

Methods
The Ludwigshafen Risk and Cardiovascular Health (LURIC) study was used in this analysis, which includes 3,316 patients (mean age 61.98 years, 69.2% male, 1722 deceased patients and 1594 alive or censored patients). After performing feature selection, 23 clinical and laboratory markers were included in our analysis. Pre-processing techniques such as SelectKbest and KNNImputer, were applied to the dataset and then it was splitted into a train and test (30%) set. The prediction of 20-year-risk of death was accomplished using the following machine learning algorithms: Logistic Regression (LR), Support Vector Machine (SVM), eXtreme Gradient Boosting (XGB) and Adaptive Boosting (AdaB). 10-fold cross validation was applied to verify the results of the models.

Results
The efficiency of each machine learning algorithm has been evaluated. XGB outperformed the others, achieving the highest accuracy (76.00%) and Area under (AUC) the Receiver Operating Characteristic Curve (ROC curve) value (0.776). The AUC value of the LR, SVM and AdaB are 0.761, 0.746 and 0.751, respectively. Figure 1 presents the ROC curve and AUC values for all models. Furthermore, the accuracy (ACC), precision, specificity, recall, F1-score and standard deviation were estimated for each classifier (Table 1).

Conclusion
We predicted all-cause mortality in patients with 20 years cardiovascular risk, using machine learning models and data of 3,316 patients. The most accurate predictive model was achieved by the eXtreme Gradient Boosting, with an accuracy equal to 76.00% and an AUC value of 0.776.

Funding Acknowledgement
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): HORIZON2020
Effect of an early invasive strategy based on time of symptom onset in patients with non-ST elevation myocardial infarction
Authors: Bae S A , Cha J J , Kim S W , Lim S , Kim J H , Joo H J , Park J H , Park S M , Hong S J , Yu C W , Lim D S , Jeong M H , Ahn T H 
Published: October 2022

Abstract

Background
A limitation of the current guidelines of the timing of invasive coronary angiography (ICA) for patients with non-ST-segment elevation (NSTE) acute coronary syndrome is based on randomization time. So far, no study has reported the clinical outcomes of invasive strategy timing based on the time of symptom onset. Herein, we aimed to investigate the effect of invasive strategy timing from the time of symptom onset on the 3-year clinical outcomes of patients with NSTE myocardial infarction (MI).

Methods and results
Among 13,104 patients from the Korea Acute Myocardial Infarction Registry-National Institutes of Health, we evaluated 5,856 patients with NSTEMI. The patients were categorized according to symptom-to-catheter (StC) time (&lt;48 h and ≥48 h). The primary outcome was 3-year all-cause mortality, and the secondary outcome was a 3-year composite of all-cause mortality, recurrent MI, and hospitalization for heart failure. Overall, 3,919 (66.9%) patients were classified into the StC time &lt;48 h group. This group had lower all-cause mortality than the StC time ≥48 h group (7.3% vs. 13.4%, p&lt;0.001). The continuous association of StC time and risk of primary and secondary endpoints showed shorter StC time (reference: 48 h), and lower adjusted hazard ratio reduction was observed. In multivariable analysis, independent predictors of delayed ICA were older age, non-specific symptoms, no use of emergency medical services, no ST-segment deviation, chronic kidney disease, and Global Registry of Acute Coronary Events score &gt;140.

Conclusion
Early invasive strategy based on the StC time improves all-cause mortality in patients with NSTEMI.

Funding Acknowledgement
Type of funding sources: None.
Value of exercise echocardiography in paradoxical low gradient severe aortic stenosis
Authors: Peteiro Vazquez J C , Bouzas-Mosquera A , Vazquez-Rodriguez J M 
Published: October 2022

Abstract

Low-flow and/or low-gradient paradoxical severe aortic stenosis (AS) is a controversial entity from a diagnostic and prognostic point of view. We aimed to assess the role of exercise echocardiography (ExE) in asymptomatic or equivocal symptoms patients with this condition.

Methods
Fifty patients (mean age 74±11 years, 70% women) with severe AS (aortic valve area [AVA] &lt;1 cm2) and low-flow low-gradient (stroke volumen &lt;35 ml/m2; mean gradient &lt;40 mmHg), or only low gradient (n=27) AS, and preserved LV ejection fraction (LVEF &gt;50%) were studied by treadmill ExE. AVA, gradients, LVEF and wall motion score index (WMSI) were assessed.

Results
Maximal achieved workload was 6.7±2.2 metabolic equivalents (METs), and LVEF (%) increased with exercise from 59±8 to 63±10. Symptoms were elicited in 14 patients (8 angina; 6 dyspnea). Five patients had wall motion abnormalities (WMAs) at rest (10%) and 18 at exercise (36%). Angiography showed CAD in 19 patients (exercise WMAs in 10) and was normal in 17 (exercise WMAs in 3). Maximum/mean transaortic gradients increased from 51±12/28±7 mmHg to 68±19/35±8 mmHg with exercise. Fourteen patients had mean gradient ≥40 mmHg with exercise (28%). There was a trend towards smaller AVA at rest and exercise in patients with exercise mean gradient ≥40 mmHg (0.78 vs 0.87 cm2, p=0.06; and 0.83 vs 0.97 cm2, p=0.07). During follow-up of 20±17 months, there were 35 events: 2 deaths, 3 admittances for cardiac failure, 2 myocardial infarctions, 26 prosthesis implantations due to worsening (with coronary intervention in 8), and 2 revascularizations. Independent predictors of events were treatment with digoxine (HR=31.3, 95% CI: 5.2–187.5, p&lt;0.001) and exercise WMSI (HR=12.3, 95% CI: 3.6–41.8, p&lt;0.001).

Conclusions
ExE offers supplementary information in low gradient severe AS. In 1/3 symptoms developed. Also in 1/3 there was significant increase in gradients. The presence of exercise WMAs was able to predict outcome.

Funding Acknowledgement
Type of funding sources: None.
P2Y12 inhibitors monotherapy in patients undergoing complex vs. non-complex percutaneous coronary intervention: a meta-analysis of randomized trials
Authors: Oliva A , Castiello D , Franzone A , Condorelli G , Colombo A , Esposito G , Stefanini G , Piccolo R 
Published: October 2022

Abstract

Background
Monotherapy with P2Y12 inhibitors (P2Y12i) is emerging as alternative strategy to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, early withdrawal of aspirin as part of P2Y12i monotherapy regimens may pose concerns in high-risk patients, such as those undergoing complex PCI.

Purpose
To evaluate the efficacy and safety of P2Y12i monotherapy after a short course of DAPT (1- to 3-month) compared with standard DAPT (≥12-month) according to PCI complexity.

Methods
We performed a meta-analysis of randomized trials using random effects models to combine hazard ratios (HRs) with 95% confidence intervals (CIs). No restrictions were applied to the type of P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) or to the definition of complex PCI. Within-trial interactions were pooled to estimate heterogeneity between complex and noncomplex PCI strata. The study protocol was registered in the PROSPERO (CRD42021291027).

Results
We screened 7,502 unique citations, of which 2,948 were screened at title and abstract level and 576 were judged potentially eligible for full-text assessment. We included in the analysis five trials (1–5) enrolling 31,627 patients, of whom 8,328 (26.3%) underwent complex PCI; characteristics of trials and patient populations are summarized in Table 1. Risk estimates for efficacy and safety outcomes associated with P2Y12i monotherapy and standard DAPT across studies included in the analysis, stratified by complex and noncomplex PCI, are reported in Figure 1. P2Y12i monotherapy compared with standard DAPT was associated with a similar risk of all-cause death, stent thrombosis, and stroke, with no evidence for interaction between complex and noncomplex PCI. We found heterogeneity in the treatment effect of P2Y12i monotherapy vs. standard DAPT with respect to myocardial infarction (P-interaction=0.027). Compared with standard DAPT, P2Y12i monotherapy decreased the risk of myocardial infarction in complex PCI (HR 0.77, 95% CI 0.60–0.99, P=0.042), but not in noncomplex PCI patients (HR 1.09, 95% CI 0.90–1.30, P=0.382). The risk of major bleeding was significantly reduced by P2Y12i monotherapy with a consistent treatment effect (P-interaction=0.699) in both complex and noncomplex PCI strata.

Conclusions
Patients undergoing complex PCI may derive more benefit and less harm from P2Y12i monotherapy after early aspirin withdrawal compared with standard DAPT, resulting in decreased risks of myocardial infarction and bleeding.

Funding Acknowledgement
Type of funding sources: None.
Real-world data from the use of ranolazine in patients with stable angina pectoris: the RANGER study
Authors: Stafylas P , Olympios C , Dermitzakis A , Efthimiadis I , Gardikiotis A , Kakouros S , Lampropoulos S , Barbetseas J , Sourgounis A 
Published: October 2022

Abstract

Background
Although ranolazine is available since years as a second-line treatment to reduce angina attacks in patients with stable angina pectoris, real-world data on effectiveness, tolerability and safety of ranolazine are limited.

Methods
A non-interventional, prospective study conducted to assess the effectiveness and safety of ranolazine. Patients eligible for enrolment had a baseline assessment between one and fourteen days after initiating ranolazine for the first time and a follow-up visit three months later. Primary endpoints comprised the weekly frequency of angina attacks, total adverse events and ranolazine discontinuation rate. Secondary endpoints included the use of short-acting nitrates, changes on the Canadian Cardiovascular Society (CCS) angina classification score and quality of life scale score (QoL).

Results
In total, 1,101 patients were enrolled in 214 sites. Mean weekly angina attacks were reduced from 3.6±2.9 to 0.4±0.9 (p&lt;0.0001) and the mean weekly consumption of short-acting nitrates decreased by 1.7±2.2 (p&lt;0.0001). CCS class and QoL were also improved (p&lt;0.0001). Adverse events were reported by 11 (1%) patients totally, while 2 of them (0.2%) were characterized as serious. Treatment was discontinued for any reason in 23 patients (2.1%) after the follow-up period. Ranolazine treatment was equally effective in all subgroups tested, with larger benefits observed in patients with more frequent angina and CCS angina class III and IV. Up-titration of ranolazine during the study improved the outcomes.

Conclusion
Ranolazine was well-tolerated and effectively reduced angina attacks with simultaneous improvement of CCS class and QoL score in patients with stable angina.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): The study was sponsored by Menarini Hellas. The study sponsor was involved in the study concept and design and in the interpretation of the data included in this publication, but not in the data collection and analysis. Menarini Hellas also funded the medical writing support for this publication.
Temporal trends in complex PCI interventions
Authors: Kheifets M , Vons S A , Bental T , Vaknin-Assa H , Perl L , Kornowski R , Levi A 
Published: October 2022

Abstract

Background
Accumulated experience combined with technological advancements in the field of complex percutaneous coronary intervention (C-PCI), have led to a gradual increase in both quantity and complexity of PCI procedures over the last 20 years. Despite the amount and frequency of these complex interventions, data regarding outcomes is lacking.

Methods
The study was based on a prospective registry of 20,301 consecutive procedures with a follow up of at least 1 year. C-PCIs were defined as at least one of the following: Chronic total occlusion (CTO), left main (LM), bifurcation or saphenous vein graft (SVG) PCI. We compared trends during four different time periods (2008–2010, 2011–2013, 2014–2016, 2017–2019). Endpoints included mortality and major adverse cardiac events [MACE: death, repeat myocardial infarction (re-MI), and target vessel revascularization (TVR)] at 1 year.

Results
The rate of C-PCI procedures has risen significantly since 2017 (p&lt;0.01), driven mainly by bifurcation and LM interventions (p&lt;0.01). At 1-year, rates of death (p&lt;0.001), re-MI (p&lt;0.001), TVR (p=0.001) and MACE (p&lt;0.001), were all significantly higher in the C-PCI group, as compared to the non-complex group. Rates of TVR (p=0.01) and MACE (p&lt;0.001) at 1-year, were significantly higher in the C-PCIs which were performed between 2008–2010 and 2011–2013, as compared to C-PCIs performed between 2014–2016 and 2017–2019. Death rates did not significantly differ between C-PCI periods.

Conclusions
Although frequency of C-PCIs is on the rise, overall outcomes become increasingly better, as compared to earlier periods. Unfortunately, this has not translated into a decrease in mortality.

Funding Acknowledgement
Type of funding sources: None.
Isolated functional tricuspid regurgitation, how define patient at-risk for event?
Authors: L'official G , Vely M , Guerin A , Chen E , Dreyfus J , Sportouch C , Oger E , Donal E 
Published: October 2022

Abstract

Introduction
Functional tricuspid regurgitation (TR) is a turning point in cardiac diseases. Symptoms typically appear late, and the optimal timing for proposing a valve repair remains a challenge. We sought to analyse the characteristics of right heart remodelling in patients with significant functional TR to identify the parameters that could be used in an easily achievable and fair prognostic model predicting clinical events.

Methods
We designed a prospective observational French multicentre study including 160 patients with significant functional TR (effective regurgitant orifice area &gt;30mm2) and LVEF &gt;40%. Clinical, echocardiographic, and ECG data were collected at baseline, and at the 1- and 2-year follow-up. The primary outcome was all-cause death or hospitalization for heart failure.

Results
At 2 years, 56 patients (35%) achieved the primary outcome. The subset with events showed more advanced right heart remodelling at baseline, but similar TR severity. Right atrial volume index (RAVI) and the TAPSE/sPAP ratio, reflecting right-ventricle-pulmonary artery coupling, were 73 mL/m2 and 0.40 versus 64.7 mL/m2 and 0.50 in the event vs event-free group, respectively (both p&lt;0.05). None among all the clinical and imaging parameters tested had a significant group × time interaction. In multivariable analysis, the model including TAPSE/sPAP ratio &gt;0.4 (OR=0.41, 95%CL 0.2 to 0.82) and RAVI &gt;60 mL/m2 (OR=2.13, 95%CL 0.96 to 4.75) permitted the fairest and most parsimonious prognostic evaluation.

Conclusion
RAVI and TAPSE/sPAP are relevant for predicting the risk for event at 2-year follow-up in patient with an isolated functional TR.

Funding Acknowledgement
Type of funding sources: None.