bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting acute kidney injury and future cardiac events using urinary liver-type fatty acid-binding protein in patients with acute myocardial infarction
Authors: Kojima K , Ohgaku A , Fujito H , Koyama Y , Arai R , Ebuchi Y , Monden M , Takei N , Tamaki T , Murata N , Fukamachi D , Okumura Y 
Published: October 2021

Abstract

Background
Urinary liver-type fatty acid-binding protein (L-FABP) has been known as a candidate biomarker for early detection of acute kidney injury (AKI). It has also been suggested to have an effective predictive value for cardiovascular mortality in patients. Therefore, this study aimed to examine the ability of urinary L-FABP in predicting AKI and future cardiovascular events in patients with acute myocardial infarction (AMI).

Methods
We evaluated consecutive 258 patients with AMI. Urinary L-FABP was measured at admission and a 2-year follow-up was performed. AKI was defined as an increase of &gt;0.3 mg/dl in serum creatinine level within 2 days after emergency percutaneous coronary intervention. The composite endpoint was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.

Results
AKI was detected in 20 patients (7.8%). Patients with AKI had significantly higher urinary L-FABP levels (68.0 μg/gCr vs 3.1 μg/gCr, p&lt;0.001) compared to those with non-AKI. Receiver operating characteristic analysis showed urinary L-FABP levels exhibited 85.7% sensitivity and 96.0% specificity, at a cutoff value of 29.7 μg/gCr. We used propensity score analyses to balance measurable confounders between patients with and without AKI, including age, left ventricular ejection fraction, an inflammation marker, renal function, and albuminuria. In logistic regression adjustment with the propensity score, urinary L-FABP level of &gt;29.7 μg/gCr was an independent predictor of AKI (p=0.001). Furthermore, high urinary L-FABP (&gt;29.7 μg/gCr) on admission correlated with an increased risk of the composite endpoints during 2-year follow-up in the Kaplan–Meier analysis (p&lt;0.001).

Conclusions
Urinary L-FABP level may be a useful biomarker for predicting not only the onset of AKI but also adverse cardiovascular events in patients with AMI.

Funding Acknowledgement
Type of funding sources: None.
The impact of age on the diagnosis of type 1 myocardial infarction using high-sensitivity cardiac troponin
Authors: Lowry M T H , Doudesis D , Kimenai D , Anand A , Mills N L 
Published: October 2021

Abstract

Background
Cardiac troponin concentrations are influenced by age and comorbidities with values above the 99th centile diagnostic threshold more common in older patients without myocardial infarction. Despite this, rule-in thresholds for myocardial infarction are applied universally regardless of age or comorbidities.

Purpose
We sought to evaluate how age and cardiovascular comorbidities influence the diagnostic performance of high-sensitivity cardiac troponin I for myocardial infarction.

Methods
In a secondary analysis of a multi-centre randomised controlled trial, we identified 45,991 consecutive patients with suspected acute coronary syndrome without ST-segment elevation myocardial infarction. The diagnostic performance of high-sensitivity cardiac troponin I measured at presentation for type 1 myocardial infarction was evaluated for the sex-specific 99th centile and thresholds three and five times this value in patients stratified by age (under 50 years, between 50 and 75 years, and over 75 years). The effect of comorbidities on diagnostic accuracy was evaluated using regression modelling.

Results
Of the 45,991 patients, 8,187 (18%) had myocardial injury of which 7,677 (94%) had a presentation troponin above the sex-specific 99th centile. Mean age of those with myocardial injury was 74 years (range 18–108). The positive predictive value (PPV) of the 99th centile was 54.6% (95% confidence interval [CI] 50.6–58.8%), 58.8% (56.9–60.6%) and 36.6% (35.1–38.2%) in patients under 50 years, between 50 and 75 years, and over 75 years, respectively. Rule-in thresholds three and five-times the 99th centile gave a higher PPV in all age groups with a PPV of 45.5% (43.1–47.8%) and 50.4% (47.6–53.2%), respectively in those aged over 75 years (Table 1). Regardless of threshold, specificity and PPV was lowest in patients over 75 years and decreased with advancing age (Figure 1). Across all age groups, the presence of heart failure resulted in the greatest decrease in PPV (36.9% [34.6–39.2%] versus 50.6% [49.3–51.8%]). Adjusting for cardiovascular comorbidities resulted in modest change in the discrimination of cardiac troponin for myocardial infarction (area under curve 0.89 vs 0.90) and did not prevent a decline in diagnostic accuracy in older patients.

Conclusion
The specificity and PPV of high-sensitivity cardiac troponin I for myocardial infarction decreases with advancing age. Cardiovascular comorbidities impact the PPV of troponin, but do not explain the decline in diagnostic accuracy with age. Clinicians should be aware of these important differences in performance by age of the diagnostic and rule-in thresholds for myocardial infarction when interpreting troponin results in older patients.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): University of Edinburgh Figure 1
Non-ST elevation myocardial infarction in patients with previous CABG: what is the best treatment option?
Authors: Oliveira L , Machado C , Almeida C , Fatima Loureiro M , Martins D ,   the Portuguese Registry of Acute Coronary Syndromes
Published: October 2021

Abstract

Background
Current European Society of Cardiology guidelines recommend an invasive strategy (IS) for the treatment of non-ST elevation myocardial infarction (NSTEMI) patients, but the clinical trials that support this recommendations included only a few patients with previous coronary artery bypass graft (CABG).

Purpose
To characterize NSTEMI patients with previous CABG who underwent medical and invasive management and to evaluate the prognostic impact of the type of strategy used.

Methods
Retrospective analysis of a cohort of patients from a multicenter national registry diagnosed with NSTEMI with a previous history of CABG between 2010 and 2021. Patient's baseline demographics, medical history and in-hospital management data was collected. Outcomes of in-hospital and six months follow-up all-cause mortality were accessed.

Results
A total of 890 patients were included in the analysis. Of these, 470 were medically managed (MM) – this group included 249 patients (53.1%) who underwent coronary angiography but did not perform any further revascularization. The remaining 420 underwent an invasive strategy (IS) and performed additional revascularization, mainly percutaneous (only 1 patient submitted to reCABG). Mean age was similar (MM 72±10 vs IS 71±10 years, p=0.147) and most patients were male (MM 81.5% vs IS 83.8%, p=0.362). MM patients had more chronic kidney disease (16.7% vs 9.9%, p=0.003), peripheral artery disease (20.5% vs 15.0%, p=0.003) and heart failure (20.5% vs 11.9%, p&lt;0.001). Main presenting symptom was chest pain in both groups, however it was more frequent in the IS group (89.4% vs 94.5%, p=0.006) and dyspnea in the MM patients (6.3% vs 3.1%). Mean left ventricle ejection fraction was similar between groups (MM 49±12% vs IS 50±11%, p=0.290). Although the GRACE risk score was available for only 124 patients, high risk patients (GRACE score &gt;140) were equally distributed among the two groups (55.9% vs 48.2%, p=0.395). An IS was associated with significant lower in-hospital mortality (4.5% vs 1.7%, OR 0.37, 95% CI 0.15–0.87, p=0.018). At six months follow-up an IS was also associated with lower mortality (6.6% vs 2.4%, HR 0.18, 95% CI 0.06–0.52, p=0.002), even after adjusting for the baseline differences (HR 0.41, 95% CI 0.20–0.85, p=0.016).

Conclusions
In this cohort of patients with NSTEMI and previous CABG, an IS was linked to better outcomes during hospitalization and during six months follow-up. Randomized clinical trials are needed to address this issue.

Funding Acknowledgement
Type of funding sources: None.
Ticagrelor or prasugrel in patients with acute coronary syndrome in relation to glomerular filtration rate
Authors: Wohrle J , Seeger J , Lahr S , Mayer K , Bernlochner I , Gewalt S , Hochholzer W , Hemetsberger R , Hapfelmeier A , Sager H , Joner M , Richardt G , Neumann F J , Schunkert H , Kastrati A ,   ISAR-REACT V
Published: October 2021

Abstract

Objectives
The aim of this study was to assess the safety and efficacy of ticagrelor versus prasugrel for patients with acute coronary syndrome (ACS) according to their glomerular filtration rate (GFR).

Background
The outcomes of ticagrelor versus prasugrel in patients with ACS according to GFR have not been defined.

Methods
Patients (n=3985) with GFR available were categorized in three groups according to the tertiles of GFR. The primary endpoint was a composite of all-cause death, myocardial infarction and stroke at 1 year.

Results
The primary endpoint occurred significantly more often in patients with low GFR compared to high GFR as well as in patients with low GFR compared to intermediate GFR (picture 1). Patients in the lowest GFR group had significantly higher ischemic and bleeding risks than patients in the intermediate (hazard ratio [HR] 1.93 and 1.68) or high GFR groups (HR 3.52 and 2.96). In the group with low GFR, the primary endpoint occurred in 103 of 677 ticagrelor patients (15.4%) and in 72 of 652 prasugrel patients (11.2%; (HR=1.45, [1.07–1.96], p=.016, picture 2). In addition, each single component of the primary endpoint and stent thrombosis were numerically lower with prasugrel compared with ticagrelor. Occurrence of myocardial infarction was 3.7% with prasugrel compared to 6.6% with ticagrelor (p=0.019). BARC 3–5 bleeding events were similar with ticagrelor and prasugrel (8.8% versus 7.1%, p=0.278). In the intermediate and high GFR group the primary endpoint and bleeding events were similar between prasugrel and ticagrelor.

Conclusions
The incidence of a composite endpoint (all-cause death, myocardial infarction or stroke) occurred less frequently in patients who received prasugrel compared to patients who received ticagrelor in the low GFR population, whereas rate of bleeding events was similar.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Supported by a grant (FKZ 81X1600501) from the German Center for Cardiovascular Research and the Deutsches Herzzentrum München, Germany. Primary endpoint according to GFRLow GFR: Prasugrel versus Ticagrelor
Body mass index and efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndromes
Authors: Lahu S , Behnes M , Ndrepepa G , Neumann F J , Sibbing D , Bernlochner I , Menichelli M , Mayer K , Richardt G , Angiolillo D J , Laugwitz K L , Schunkert H , Schuepke S , Kastrati A , Akin I 
Published: October 2021

Abstract

Background
The efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndromes (ACS) according to body mass index (BMI) remain unknown.

Purpose
To assess the efficacy and safety of ticagrelor versus prasugrel in patients with ACS according to BMI.

Methods
This post-hoc analysis of the ISAR-REACT 5 trial included 3987 patients with BMI data available. BMI was grouped in 3 categories: low (BMI&lt;25 kg/m2, n=1084), intermediate (BMI ≥25 to &lt;30 kg/m2, n=1890) and high (BMI≥30 kg/m2, n=1013). The primary endpoint was the 12-month incidence of all-cause death, myocardial infarction, or stroke. The secondary endpoint was the 12-month incidence of Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding.

Results
There was no significant treatment arm-by-BMI interaction regarding the primary endpoint (Pint=0.578). However, the primary endpoint occurred in 63 patients assigned to ticagrelor and 39 patients assigned to prasugrel in the low BMI group (11.7% vs. 7.5%; hazard ratio [HR]=1.62; 95% confidence interval [CI], 1.09–2.42; P=0.018), 78 patients assigned to ticagrelor and 58 patients assigned to prasugrel in the intermediate BMI group (8.3% vs. 6.2%; HR=1.36 [0.97–1.91]; P=0.076), and 43 patients assigned to ticagrelor and 37 patients assigned to prasugrel in the high BMI group (8.6% vs. 7.3%; HR=1.18 [0.76–1.84]; P=0.451). BARC type 3 to 5 bleeding events did not differ between ticagrelor and prasugrel in patients with low (6.5% vs. 6.6%), intermediate (5.6% vs. 5.0%), or high (4.4% vs. 2.8%) BMI.

Conclusions
BMI of patients with ACS did not impact significantly on the treatment effect of ticagrelor vs. prasugrel in terms of both efficacy and safety.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Center for Cardiovascular Research;Deutsches Herzzentrum München, Germany
Indirect effects of COVID-19 Pandemic in ST-segment elevation myocardial infarction: insights from a multicentric national survey
Authors: Pereira H , Cale R , Farto-Abreu P , Pereira E , On Behalf Of Stent Save A Life Initiative S S L ,   Stent Save a Life
Published: October 2021

Abstract

Objective
Coronavirus disease 2019 (COVID-19) pandemic may have indirect consequences in ST-segment elevation myocardial infarction (STEMI) outcomes due to difficulties in healthcare access, but also due to reperfusion delays. The objective of this study was to evaluate the performance indicators in STEMI during the early phase of the lockdown following the COVID-19 pandemic.

Methods
The “patient delay” and the “system delay” were evaluated in 312 patients with suspected STEMI, in the period of the first State of Emergency in Portugal, through a survey called “Moment COVID” implemented within 18th March to 2 May 2020, in 18 national centers of Interventional Cardiology where PPCI is carried out 24/7. These patients were compared with a historical cohort of 267 patients from the 5th year after integration of SFL Initiative in Portugal (Moment 2015) in which the same survey was applied. Patients with late presentation of STEMI (&gt;12 hours of symptoms onset) were excluded from this analysis.

Results
In “Moment COVID” there was a trend towards a longer “patient delay” (incremental median 20 min; p=0.059) and a significant longer system-delay (incremental median 17 min; p=0.033) compared to the historical cohort of “Moment 2015”. Consequently, times to revascularization tended to be longer (incremental median 26 min; p=0.074). Indeed, in “Moment COVID” patients were less compliant with the times recommended by the European guidelines: door-to-balloon time &lt;60 min was achieved in 47.6% of patients compared to 57.0% (p=0.052) in “Moment 2015” and system-delay &lt;90 min in 13.9% compared to 21.8% (p=0.033).

Conclusion
These results from a multicentric national analysis demonstrated a trend to longer time from symptom onset to request healthcare system assistance and a significantly longer time from first medical contact to revascularization among patients with STEMI during COVID-19 pandemic. This delay for treatment could negatively impact the STEMI prognosis at the long-term.

Funding Acknowledgement
Type of funding sources: None.
Long-term follow-up of patients with MINOCA (myocardial infarction with unobstructed coronary arteries) undergoing intracoronary spasm provocation testing
Authors: Pirozzolo G , Seitz A , Sechtem U , Bekeredjian R , Ong P 
Published: October 2021

Abstract

Background
Up to 30% of patients presenting with acute coronary syndrome undergoing coronary angiography are found to have no culprit lesion. Among them, epicardial or microvascular spasm can be diagnosed in ∼50% of patients undergoing provocative testing. While prognostic data in patients with coronary spasm and stable angina are abundant, the outcome of patients with myocardial infarction and unobstructed coronaries (MINOCA) and coronary spasm is not clear.

Purpose
The aim of this study was to investigate the prognosis of a cohort of patients presenting with MINOCA undergoing intracoronary acetylcholine (ACH) spasm testing.

Methods
We evaluated consecutive patients with MINOCA undergoing acetylcholine testing to detect epicardial or microvascular spasm from 2014 to 2017. Other aetiologies for MINOCA such as myocarditis, supraventricular tachycardia, pulmonary embolism etc. were excluded. Data regarding mortality (cardiac/non-cardiac), nonfatal myocardial infarction (MI), repeated coronary angiography and percutaneous coronary intervention (PCI) were recorded.

Results
Of 112 patients in our study, follow-up data were available for 96 patients (86%, 51% women, mean age 63±13 years). Acetylcholine testing was positive in 51 (53%) patients. Among patients with a positive test, epicardial spasm was detected in 26 (51%) and microvascular spasm in 25 (49%) patients. After a median follow-up of 5±3.5 years, 7 deaths (7%) and 20 nonfatal myocardial infarctions (21%) occurred. Moreover, 19 patients (20%) underwent coronary angiography and 9 patients (9%) received a PCI. Comparisons of the Kaplan–Meier curves by log-rank test showed that patients with positive acetylcholine test had a worse outcome compared to those with a negative test in terms of death from any cause (p=0.01), myocardial infarction (p=0.03) and repeated coronary angiography (p=0.05).

Conclusion
This follow-up study shows that prognosis of MINOCA patients with coronary spasm on provocative testing is worse compared to patients with an uneventful test. The results underline the potential prognostic value of spasm testing in MINOCA patients.

Funding Acknowledgement
Type of funding sources: None.
Long-term prognostic factors of coronary artery disease patients after out-of-hospital cardiac arrest
Authors: Nitta G , Matsuda J , Lee T , Kato S , Hada Y , Inaba O , Matsumura Y , Nozato T , Ashikaga T , Sasano T 
Published: October 2021

Abstract

Background
The long-term prognosis of survival in patients with out-of-hospital cardiac arrest (OHCA) with coronary artery disease (CAD) remains poor.

Methods
There were 2391 out-of-hospital cardiac arrest (OHCA) patients transferred to 2 hospitals. We included 405 cardiovascular arrest patients, who got return of spontaneous circulation (ROSC) from January 2015 to December 2018. Among them, 204 patients had CAD that caused OHCA (39%: multi-vessel disease, 19%: chronic total occlusion (CTO), 13%: vasospastic angina (VSA)). To predict mortality, we investigated patients' characteristics, pre-hospital information and findings of CAG.

Results
At 1-year later, 104 patients (51%) survived. Younger age (P&lt;0.001), VF survivor (P&lt;0.001), pre-hospital ROSC (P&lt;0.001), bystander CPR (P=0.013), without ECMO (P&lt;0.001), lower lactate level on admission (P&lt;0.001), and higher geriatric nutritional risk index score (P&lt;0.001) were associated with low 1-year mortality, while with ST-segment elevation (P=0.778), BMI level (P=0.344), and sex (0.401) were not. And in the findings of CAG, the past history of CAD (P=0.049), the higher number of coronary vessel disease (P=0.003) such as multi-vessel disease (P=0.022), higher SYNAX score (P=0.016), and larger infarct size (max CK level; P=0.013, max CK-MB level; P&lt;0.001) were associated with high 1-year mortality. On the other hand, acute coronary syndrome (P=0.300), any coronary lesion (RCA (P=0.447), LAD (P=0.089), LCX (P=0.096), or LMT (P=0.842)), and with CTO lesion (P=0.140) were not associated. Zero-vessel disease (VSA, P=0.001) had lower mortality among the CAD patients. In the multivariate Cox proportional hazards model, age (hazards ratio; HR: 1.03, 95%confidence interval (CI) 1.00–1.06, P&lt;0.001) and bystander CPR (HR: 0.36, 95% CI 0.20–0.65, P&lt;0.001) were the independent predictors of mortality.

Conclusions
Younger age and pre-hospital support after OHCA with CAD were the predictors of low mortality. Pre-hospital information, systemic condition on arrival, or anatomical coronary complexity were important to predict low mortality.

Funding Acknowledgement
Type of funding sources: None.
Phenotypic characterization of rabbit model for aortic valve stenosis: a novel medial calcification paradigm
Authors: Anousakis-Vlachochristou N , Mavroidis M , Makridakis M , Miliou A , Kontostathi G , Agapaki A , Mouchtouri E , Zigouri L , Konstantinou G , Lampas E , Kalogera S , Vlahou A , Cokkinos D , Tsioufis K , Toutouzas K 
Published: October 2021

Abstract

Introduction
Calcific aortic valve stenosis (CAVS) is the result of subtle, chronic inflammation and osteoblastic differentiation. As we lack human specimens of the early stages, reliable and reproducible animal models are needed to facilitate research. We previously demonstrated the ability of a novel rabbit CAVS vitamin D2 toxicity protocol to produce calcification and valve stenosis (1). We sought to characterize the phenotype of the model at the final stage.

Methods
Twelve New Zealand Rabbits were randomized 1:1 to control (normal chaw) and experimental group (normal chaw+1% cholesterol+3.500 I.U.s Vitamin D2, in oil in a biscuit) for 7 weeks. Animals were sacrificed and aortic valve cusps were snap frozen or formalin-fixed paraffin embedded. Cusps were then mechanically homogenized in buffer optimized for protein extraction and total protein measured with Bradford method. Part of the extract was subjected to trypsinization, in-gel digestion and untargeted LC-MS/MS. The rest was used to quantitate BMP-2 with total protein-normalized sandwitch competitive ELISA. Thin tissue sections were stained with Masson's trichrome, Von Kossa and H&E. Osteopontin, Bone sialoprotein II (BSPII), tissue non-specific alkaline phosphatase (TNAP) and osteocalcin (OCN) were detected on tissue with immunohistochemistry. Femoral bones from the same animals served as positive controls.

Results
Aortic valve cusp demonstrate large areas of collagen degradation and calcification in the medial layer, almost sparing the intima. Osteopontin deposits were colocalized with the calcification area in the media, whereas BSPII, TNAP and OCN were not expressed in the lesion, although present in bones. Similarly, BMP-2 levels were not significantly different between groups (experimental = 43.45 vs controls = 62.75 pg/ml, Mann-Whitney U test p=0.496). Proteomic analysis revealed a set of 96 differentially expressed proteins between cases and controls, interestingly including sortilin, osteonectin, beta-crystallin A2, Matrix Gla protein, Na/H exchanger 3, V-type H ATPase subunit D, Y-box binding protein.

Conclusion
The novel rabbit vitamin D2 toxicity protocol leads to excessive medial calcification of the aortic valve, with overexpression of osteopontin but without other classic markers of CAVS. Proteomics analysis reveals novel pathways with pathophysiological implications for the model and medial calcification.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Hellenic Cardiology Society, Hellenic Heart Foundation