Surrogate Markers of Neutrophil Extracellular Trap Formation are Associated with Ischemic Outcomes and Platelet Activation after Peripheral Angioplasty and Stenting

Neutrophil extracellular traps (NETs) are supposed to play a central role in atherothrombosis. We measured circulating citrullinated histone H3 (H3Cit) and cell-free DNA (cfDNA), which serve as surrogate markers of NET formation, in 79 patients with peripheral artery disease (PAD) following infrainguinal angioplasty with stent implantation. Analysis of cfDNA and H3Cit was performed using Quant-iT™ PicoGreen® dsDNA Assay Kit or an ELISA, respectively. Within two years of follow-up, the primary endpoint defined as nonfatal myocardial infarction, stroke or transient ischemic attack, cardiovascular death, and >80% target vessel restenosis occurred in 34 patients (43%). Both H3Cit (HR per 1-SD: 2.72; 95% CI: 1.2–6.3; p = 0.019) and cfDNA (HR per 1-SD: 2.15; 95% CI: 1.1–4.2; p = 0.028) were associated with the primary endpoint in a univariate Cox regression analysis. Multivariate linear regression analyses showed associations between cfDNA and platelet surface expression of P-selectin (p = 0.006) and activated glycoprotein IIb/IIIa (p < 0.001) in response to arachidonic acid (AA) after adjustment for age, sex, clinical risk factors, and inflammatory markers. H3Cit was also associated with P-selectin expression in response to thrombin-receptor activating peptide (p = 0.048) and AA (p = 0.032). Circulating H3Cit and cfDNA predict ischemic outcomes after peripheral angioplasty with stent implantation, and are associated with on-treatment platelet activation in stable PAD.

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Association of Soluble Suppression of Tumorigenesis 2 (sST2) With Platelet Activation, Monocyte Tissue Factor and Ischemic Outcomes Following Angioplasty and Stenting

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2020.605669 ◽

2020 ◽

Vol 7 ◽

Author(s):

Stefan Stojkovic ◽

Svitlana Demyanets ◽

Christoph W. Kopp ◽

Christian Hengstenberg ◽

Johann Wojta ◽

...

Keyword(s):

Cardiovascular Disease ◽

Tissue Factor ◽

Platelet Activation ◽

Primary Endpoint ◽

Stent Implantation ◽

Target Lesion ◽

Platelet Surface ◽

Soluble P ◽

Angioplasty And Stenting ◽

Circulating Levels

Background: Peripheral artery disease (PAD) patients undergoing infrainguinal angioplasty with stenting suffer high rates of target lesion restenosis and ischemic events. Blood-based prognostic markers in these patients are currently limited. The IL-33/ST2-system is involved in atherothrombosis. Soluble ST2 has been proposed as a biomarker in patients with cardiovascular disease.Aim: To investigate the association of sST2 with platelet activation and monocyte tissue factor (TF) in 316 patients undergoing elective angioplasty and stenting for cardiovascular disease, and its predictive value for ischemic outcomes following infrainguinal angioplasty with stent implantation in 104 PAD patients within this cohort.Methods and Results: Circulating levels of sST2, platelet surface P-selectin, monocyte TF expression as well as soluble P-selectin were determined in 316 consecutive patients on dual antiplatelet therapy following angioplasty and stenting. sST2 was independently associated with soluble P-selectin (B = 6.4, 95% CI 2.0–10.7, p = 0.004) and TF expression (B = 0.56, 95% CI 0.02–1.1, p = 0.041) but not with platelet surface P-selectin (B = 0.1, 95% CI −0.1–0.3, p = 0.307) after adjustment for age, sex, clinical risk factors and inflammatory parameters. During the follow-up of 24 months, the primary endpoint occurred in 41 of 104 PAD patients (39.4%). However, circulating levels of sST2 did not predict the primary endpoint in PAD patients (HR 1.1, 95% CI 0.76–1.71, p = 0.527).Conclusion: sST2 is associated with soluble P-selectin and monocyte TF expression in atherosclerosis but not with ischemic outcomes following infrainguinal angioplasty with stent implantation for PAD.

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Clinical significance of Q waves in ischemic cardiomyopathy

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.340 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

E Rodenas Alesina ◽

P Jordan ◽

L Herrador ◽

C Espinet-Coll ◽

N Pizzi ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Primary Endpoint ◽

Ischemic Cardiomyopathy ◽

Cox Regression ◽

Cox Model ◽

Cardiovascular Death ◽

P Value ◽

Heart Failure Hospitalization ◽

Total Cohort

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): CIBER-CV AIMS The scintigraphic translation of Q waves in patients with ischemic cardiomyopathy and LVEF < 40% has not yet been assessed. The aim of this study was to explore the relationship between Q waves and necrotic tissue and to analyze their impact in prognosis. METHODS AND RESULTS A retrospective study enrolling 487 consecutive patients (67,0 [57,4 – 75,4] years), with ischemic cardiomyopathy, LVEF <40% and narrow QRS who underwent stress-rest SPECT was conducted. Patients with Q waves (320 patients [65,7%]) had less comorbidity and ischemia, but more necrosis. Q waves correlated poorly with lack of viability (AUC = 0,63) and were independently associated with the subendocardial extent of the necrosis. After a follow-up of 5,07 years, the primary outcome (cardiovascular death, heart failure hospitalization or myocardial infarction) occurred in 192 (39,4%) patients, without differences between groups in multivariate analysis. After accounting for non-cardiovascular death as a competitive risk, the interaction between >10% of ischemia and revascularization remained in Cox model both in the total cohort (aHR= 0,46 [0,24 – 0,86]), and in patients with Q waves (aHR = 0,27 [0,11–0,69]). CONCLUSION Patients with ischemic cardiomyopathy with Q waves have larger subendocardial scarring and more transmural necrosis, although correlation between Q waves and transmural scarring is poor. Revascularization if >10% ischemia is present is associated with a better prognosis. Ischemia burden should be assessed and accordingly treated in these patients, and no differences in management should be made in the presence of Q waves. Table 1. Cox proportional hazards model Total cohort (N = 471) Patients with Q waves (N = 315) aHR p-value 95% CI aHR p-value 95% CI Age (per year) 1,02 0,007 1,01 - 1,04 n.s. Diabetes mellitus 1,35 0,047 1,00 - 1,81 1,54 0,016 1,09 - 2,20 eGFR < 60 ml/min 1,59 0,005 1,15 - 2,21 1,96 <0,001 1,36 - 2,82 Previous HF hospitalization 1,71 0,002 1,23 - 2,38 1,76 0,007 1,17 - 2,64 Previous PCI 1,32 0,069 0,98 - 1,78 n.s. Previous CABG n.s. 1,77 0,009 1,15 - 2,72 Angina or dyspnea 1,68 0,001 1,24 - 2,28 1,71 0,004 1,19 - 2,46 Indexed TDV (per quartile) 1,16 0,047 1,02 - 1,33 n.s. Revascularization*ischemia > 10% 0,46 0,015 0,24 - 0,86 0,27 0,006 0,11 - 0,69 Cox regression for the primary endpoint (cardiovascular death, heart failure hospitalization or myocardial infarction), accounting for non-cardiovascular death as a competitive risk. Abstract Figure. Survival for the primary endpoint

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A stand-alone structured educational programme after myocardial infarction: a randomised study

Heart ◽

10.1136/heartjnl-2020-318414 ◽

2021 ◽

pp. heartjnl-2020-318414

Author(s):

Georgios Giannopoulos ◽

Sofia Karageorgiou ◽

Dimitrios Vrachatis ◽

Ioannis Anagnostopoulos ◽

Maria S Kousta ◽

...

Keyword(s):

Myocardial Infarction ◽

Primary Endpoint ◽

Cardiovascular Events ◽

Cox Regression ◽

Intervention Group ◽

Educational Programme ◽

Lifestyle Changes ◽

Cerebrovascular Event ◽

Primary Analysis ◽

Cox Regression Analysis

BackgroundAcute myocardial infarction (MI) is a major clinical manifestation of coronary artery disease. Post-MI morbidity and mortality can be reduced by lifestyle changes and aggressive risk factor modification. These changes can be applied more effectively if the patient is actively involved in the process. The hypothesis of this study was that an educational programme in post-MI patients could lead to reduced incidence of cardiovascular events.MethodsPost-MI patients were prospectively randomised into two groups. Patients in the intervention arm were scheduled to attend an 8-week-long educational programme on top of usual treatment, while controls received optimal treatment. The primary endpoint was the composite of all-cause death, MI, cerebrovascular event and unscheduled hospitalisation for cardiovascular causes. Endpoint adjudication was blinded.Results329 patients (238 men) were included, with a mean follow-up time of 17±4 months. In the primary analysis, mean primary end point-free survival time was 597 days (95% CI 571 to 624) in controls, compared with 663 days (95% CI 638 to 687) in the intervention group (p<0.001). The HR in the univariate Cox regression analysis was 0.48 (95% CI 0.32 to 0.73; p=0.001). The raw rates of the primary endpoint were 20.8% (6 deaths, 13 MIs, 2 strokes and 14 hospitalisations) vs 36.6% (8 deaths, 22 MIs, 7 strokes and 22 hospitalisations), respectively (OR 0.46, 95% CI 0.28 to 0.74; p=0.002).ConclusionThese results suggest that a relatively short adult education programme offered to post-MI patients has beneficial effects, resulting in reduced risk of cardiovascular events.Trial registration numberNCT04007887.

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Abstract TP431: Association of Systolic Blood Pressure and Cardiovascularrisk According to Hemoglobin Concentration

Stroke ◽

10.1161/str.51.suppl_1.tp431 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Jun Young Chang ◽

Se Young Jang ◽

Sun-uck Kwon

Keyword(s):

Blood Pressure ◽

Cardiovascular Risk ◽

Systolic Blood Pressure ◽

Cox Regression ◽

Hemoglobin Concentration ◽

Cardiovascular Death ◽

Normal Range ◽

Cox Regression Analysis ◽

Hazard Ratios ◽

Hb Concentration

Introduction: We evaluated whether the optimal cutoff of blood pressure to reduce cardiovascular risk is different according to hemoglobin (Hb) concentration and its changing pattern using the National Health Insurance Service-Health Screening Cohort. Methods: The study population consisted of individuals who underwent both 2002-2003 and 2004-2005 health examinations. Individuals who were diagnosed with cardiovascular disease or who died before index date of 1 January 2006 were excluded. The primary outcome of the study was the association between systolic blood pressure (SBP) and MACE (composite of myocardial infarction, stroke, and cardiovascular death) according to Hb concentration. Hazard ratios (HR) were calculated using Cox regression analysis adjusted for age and sex. Results: A total of 290573 were included in the analysis. During the follow up period from 1 January 2006 to 31 December 2013, a total of 18292 experienced MACE. There was a significant interaction between SBP and Hb concentration with regard to cardiovascular diseases (p for interaction= 0.07). Among the subjects with Hb <10, a significant increment of MACE was observed when SBP ≥140 mmHg. HR for MACE increased when SBP ≥130mmHg among the subjects with 10≤ Hb <11 and 11≤ Hb <12. HR for MACE increased when SBP ≥ 120 mmHg among the subjects with 12≤ Hb <13, 13≤ Hb <15, and 15≤ Hb. Cardiovascular risk was the lowest in SBP below 120mmHg and cut off value for increasing cardiovascular risk was 120 mmHg or above in subjects who maintain normal range of hemoglobin level and whose hemoglobin concentration changed from anemia to normal range. However, individuals who maintain anemic state and whose hemoglobin concentration changed from normal range to anemia, SBP threshold for increasing cardiovascular risk was equal or above 130 mmHg . Conclusion: The threshold of SBP which increases cardiovascular risk may be different according to the hemoglobin concentration and change pattern of hemoglobin.

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MO159CHA2DS2-VASC SCORE AS A PREDICTOR OF CARDIOVASCULAR MORTALITY IN CHRONIC KIDNEY DISEASE PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab092.0037 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Nina Vodošek Hojs ◽

Robert Ekart ◽

Sebastjan Bevc ◽

Nejc Piko ◽

Radovan Hojs

Keyword(s):

Chronic Kidney Disease ◽

Regression Analysis ◽

Cardiovascular Risk ◽

Kidney Disease ◽

Cardiovascular Mortality ◽

Cox Regression ◽

High Sensitivity ◽

Cardiovascular Death ◽

Cox Regression Analysis

Abstract Background and Aims Cardiovascular mortality is high in chronic kidney disease (CKD) patients. Recognizing patients with higher cardiovascular risk might help in their treatment. CHA2DS2-VASc score was originally used to predict cerebral infarction in patients with atrial fibrillation (AF). However, it is also useful in predicting outcome in different cardiovascular conditions, independent of the presence of AF. Therefore, the aim of our research was to assess the role of CHA2DS2-VASc score in cardiovascular mortality in CKD patients. Method Eighty-seven non-dialysis CKD patients from our outpatient clinic were included. At the time of inclusion, medical history data and standard blood results were collected and CHA2DS2-VASc score was calculated. Patients were followed for assigned time or until their death. Mean follow-up time was 1696.45±564.60 days. Results Descriptive statistics of our patients are presented in table 1. During follow-up 11 patients suffered from cardiovascular death. Univariate Cox regression analysis showed that CHA2DS2-VASc score is a significant predictor of cardiovascular mortality (HR: 2.19, CI: 1.42-3.37, p=0.001). In multivariate Cox regression analysis in which CHA2DS2-VASc score, serum creatinine, urinary albumin/creatinine, haemoglobin, high sensitivity CRP and intact PTH were included, CHA2DS2-VASc score was an independent predictor of cardiovascular mortality (HR: 2.04, CI: 1.20-3.45, p=0.008) (table 2). Conclusion CHA2DS2-VASc score is a simple and quick way to identify cardiovascular risk in CKD patients.

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Prognostic significance of carbohydrate antigen 125 in acute heart failure: a prospective comparative study with N-terminal pro-B-type natriuretic peptide

10.21203/rs.3.rs-864855/v1 ◽

2021 ◽

Author(s):

Ji Zhang ◽

Wenhua Li ◽

Gaojun Cai ◽

Jianqiang Xiao ◽

Jie Hui ◽

...

Keyword(s):

Heart Failure ◽

Adverse Events ◽

Acute Heart Failure ◽

Natriuretic Peptide ◽

Primary Endpoint ◽

Cox Regression ◽

Prognostic Significance ◽

Carbohydrate Antigen ◽

Cox Regression Analysis ◽

Carbohydrate Antigen 125

Abstract Background In acute heart failure (AHF), elevated carbohydrate antigen 125 (CA125) and N-terminal pro-B-type natriuretic peptide (NTproBNP) have shown to correlate with adverse events. We sought to quantify their prognostic usefulness in predicting the 6-month combined endpoint of death/heart failure readmission. Methods The study includes 352 patients admitted for AHF. The primary endpoint was 6-month combined endpoint of death/AHF rehospitalization. CA125 and NTproBNP were dichotomized according to the best cut-offs to predict 6-month primary endpoint. By multivariate Cox regression analysis, the independent association of CA125 and NTproBNP with the primary endpoint was assessed, and their incremental prognostic utility evaluated by net reclassification improvement (NRI) and integrated discrimination improvement (IDI) index. Results A total of 47 (13.4%) deaths and 113 (32.1%) AHF rehospitalizations were identified at 6-month follow-up. The subjects with CA125 ≥ 39.7 U/ml and NTproBNP ≥ 3900 pg/ml had significantly higher cumulative event rates (56.1% vs. 33.3% and 53.3% vs. 33.8%, both P < 0.001). Elevated CA125 (HR 1.93; 95%CI [1.32–2.83]; P = 0.001) was associated with higher HR than NTproBNP ≥ 3900 pg/ml (HR 1.71; 95%CI [1.19–2.48]; P = 0.004) after adjusting for established risk factors. Elevated CA125 still independently predicted adverse events when both CA125 and NTproBNP were entered together in the same multivariate model. Furthermore, risk reclassification analyses demonstrated significant improvements in NRI of 22.3% (P = 0.014) and IDI of 2.7% (P = 0.012) when adding CA125 to the base model + NTproBNP. Conclusions Elevated CA125 and NTproBNP predicted adverse outcomes in AHF patients. CA125 added prognostic value to NTproBNP, and thus, their combination conferred greater predictive capacity.

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Abstract 3095: Prognostic Significance Of Post-revascularisation Irreversible Myocardial Injury Detected By Cardiovascular Magnetic Resonance Imaging

Circulation ◽

10.1161/circ.116.suppl_16.ii_694 ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Joseph B Selvanayagam ◽

Kazem Rahimi ◽

Adrian Banning ◽

Adrian S Cheng ◽

Tammy J Pegg ◽

...

Keyword(s):

Primary Endpoint ◽

Myocardial Injury ◽

Cox Regression ◽

Univariate Analysis ◽

Prognostic Significance ◽

Total Mortality ◽

Secondary Endpoint ◽

Consecutive Series ◽

Post Intervention ◽

Cox Regression Analysis

Background The prognostic significance of revascularization procedure related myocardial injury is uncertain. Delayed enhancement CMR (DE-CMR) has been shown to reliably identify areas of irreversible myocardial injury. We evaluated the prognostic significance of procedure related myocardial injury in a consecutive series of patients undergoing high risk PCI or CABG. Methods/Results 152 patients underwent DE-CMR pre and 1– 6 days post elective PCI or CABG. Primary endpoint was defined as total mortality, non-fatal MI, ventricular arrhythmia terminated by ICD (VA), and unstable angina or heart failure requiring hospitalization. Secondary endpoint was the composite of total mortality, non-fatal MI and VA. During a median follow-up of 2.9 years, 27 patients (18%) reached the primary endpoint and 12 patients (8%) the secondary endpoint. 49 patients (32%) had evidence of new myocardial hyperenhancement (HE) with a median mass of 5.0g (IQR 4.8 –7.1). In a univariate analysis, age, LV EF post intervention, and presence of new HE were predictive of the primary outcome. Elevated troponin (at 24 h) showed a trend towards poorer outcome. In a multivariate Cox regression analysis only age and presence of new HE (HR 2.7, 95% CI 1.1, 5.8) remained independently correlated with occurrence of the primary endpoint. New myocardial HE was the single independent predictor of the composite secondary endpoint (HR 4.2 95% CI 1.2, 16.1). Conclusion Even small amounts of procedure-related myocardial injury are associated with poorer medium term clinical outcomes. CMR identified myocardial injury may be a stronger prognostic marker than cardiac troponin in the setting of coronary revascularisation.

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Long-Term Prognosis after Myectomy in Hypertrophic Obstructive Cardiomyopathy with Severe Left Ventricular Hypertrophy

Cardiology ◽

10.1159/000484628 ◽

2018 ◽

Vol 139 (2) ◽

pp. 83-89 ◽

Cited By ~ 1

Author(s):

Shuoyan An ◽

Chaomei Fan ◽

Yinjian Yang ◽

Fei Hang ◽

Zhimin Wang ◽

...

Keyword(s):

Left Ventricular Hypertrophy ◽

Ventricular Hypertrophy ◽

Cox Regression ◽

Hypertrophic Obstructive Cardiomyopathy ◽

Cardiovascular Death ◽

Left Ventricular ◽

Medical Group ◽

Cox Regression Analysis

Objectives: Patients with hypertrophic obstructive cardiomyopathy (HOCM) and severe left ventricular hypertrophy (maximal left ventricular wall thickness ≥30 mm) are at high risk of sudden cardiac death (SCD). In this study, we aimed to determine whether HOCM patients with severe hypertrophy had a lower incidence of SCD after myectomy. Methods: HOCM patients with severe hypertrophy were consecutively enrolled from Fuwai Hospital in China between 2000 and 2013. Long-term outcomes were retrospectively compared between the 2 groups, namely the myectomy group and medical group. Results: A total of 244 patients (118 in the myectomy group and 126 in the medical group) were involved. The mean follow-up durations for the myectomy and medical groups were 5.07 ± 3.73 and 6.23 ± 4.15 years, respectively. During the follow-up period, the annual cardiovascular mortality rate was 0.84% in the myectomy group and 2.04% in the medical group (p = 0.041). The annual SCD rate was 0.33% in the myectomy group and 1.40% in the medical group (p = 0.040). Multivariate Cox regression analysis showed that myectomy was independently associated with lower rates of cardiovascular death and SCD. Conclusions: In HOCM patients with severe hypertrophy, those that underwent myectomy had a lower risk of cardiovascular death and SCD than those treated with medicines only.

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3293Atherothrombotic risk and outcomes following guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome:a post-hoc analysis of the TROPICAL-ACS trial

European Heart Journal ◽

10.1093/eurheartj/ehz745.0058 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

K Rizas ◽

S Farhan ◽

Z Huczek ◽

B Merkely ◽

R Hein-Rothweiler ◽

...

Keyword(s):

Primary Endpoint ◽

Treatment Strategy ◽

Conventional Treatment ◽

Cox Regression ◽

Control Group ◽

Antiplatelet Treatment ◽

P2y12 Inhibitor ◽

Cox Regression Analysis ◽

Coronary Syndrome ◽

Inhibitor Treatment

Abstract Background A de-escalation of P2Y12-inhibitor treatment guided by platelet function testing (PFT) has been identified as a safe and alternative treatment strategy in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). However, no specific data are available on the efficacy of such strategy in patients with high atherothrombotic risk (ATR). Purpose To investigate the safety and efficacy of guided de-escalation of P2Y12-inhibitor treatment in patients with low- vs. high-ATR. Methods The TROPICAL-ACS trial randomized 2,610 biomarker-positive ACS patients 1:1 to either conventional treatment with prasugrel for 12 months (control group) or to a PFT guided de-escalation treatment strategy (guided de-escalation group). The primary endpoint was defined as the composite of cardiovascular mortality (CVM), myocardial infarction (MI), stroke, and clinically overt bleeding (bleeding ≥ grade 2 according to the BARC criteria). The ischemic endpoint was defined as the composite of CVM, MI or stroke. We used semi-parametric Cox regression analysis and interaction testing to assess the effect of low- vs. high-ATR on the primary and ischemic endpoints. High-ATR was defined as one of the following: (i) age ≥65 years or (ii) age <65 and either history of peripheral artery disease or at least two of the following risk-factors: diabetes mellitus, current smoking or renal dysfunction. Results Patients with high- (n=990) versus low-ATR (n=1,620) exhibited a higher risk for the primary endpoint (11.0% vs. 6.7%; HR 1.67; 95% CI 1.28–2.18; p<0.001). Guided de-escalation was non-inferior to conventional treatment for the primary endpoint in both patients with high- (10.5% vs. 11.5%; pnon-inferiority = 0.029; Figure 1A) and low-ATR (5.6% vs. 7.7%; pnon-inferiority=0.001; Figure 1B). Moreover, there was no significant interaction in the prognostic value of guided de-escalation between high- and low-ATR groups for both the primary (HR 0.90 [0.61–1.32]; p=0.586 in patients with high-ART vs. 0.71 [0.48–1.04; p=0.082 in patients with low-ATR; pinteraction= 0.394) and combined ischemic endpoints (HR 0.83 [0.44–1.56]; p=0.567 in patients with high-ATR vs. 0.68 [0.35–1.34]; p=0.262 in patients with low-ATR; pinteraction =0.666). Kaplan-Meier curves Conclusion A guided DAPT de-escalation strategy appears to be safe and effective in ACS patients regardless of the atherothrombotic risk. Further studies are needed for refining antiplatelet treatment strategies in ACS patients with varying levels of atherothrombotic risk. Acknowledgement/Funding Klinikum der Universität München, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.

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The association of anemia with high-sensitive cardiac troponin and its influence on the ESC 0/1h and 0/3h algorithms to triage patients with suspected acute myocardial infarction

European Heart Journal ◽

10.1093/ehjci/ehaa946.1690 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

P.M Haller ◽

J.T Neumann ◽

N.A Soerensen ◽

A Gossling ◽

T.S Hartikainen ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Predictive Value ◽

Cox Regression ◽

Similar Efficacy ◽

Cardiovascular Death ◽

Funding Source ◽

Cardiovascular Research ◽

Cox Regression Analysis ◽

Suspected Acute Myocardial Infarction

Abstract Introduction According to the 4th Universal Definition of Myocardial Infarction (UDMI), anemia may cause acute and chronic myocardial injury indicated by elevated high-sensitive troponin (hs-cTn) concentrations, with unknown influence on triaging patients with suspected acute myocardial infarction (AMI). Purpose To investigate the influence of anemia on hs-cTnI and the diagnostic performance of the ESC 0/1 and 0/3 hour (h) algorithms. Methods Patients with suspected AMI were prospectively enrolled and stratified based on the hemoglobin (Hb) concentration at admission (females <12 g/dl, males <13g/dl). Hs-cTnI was measured at presentation, 1 and 3h later. Three independent cardiologists adjudicated the final diagnoses according to the 4th UDMI. Patients with ST-elevation AMI were excluded. Our primary endpoints were the safety to rule-out (negative predictive value [NPV]) and the efficacy to rule-in (positive predictive value [PPV]) AMI. Patients were followed for up to 4 years to assess all-cause mortality. Results We included 2,223 patients (64.1% males, age 65 [52; 75]) of whom 415 (18.7%) had anemia. The prevalence of AMI was numerically different for patients with and without anemia (16.4% and 12.9%, p=0.072). Hs-cTnI concentrations were significantly higher in patients with anemia and no AMI (p<0.001 for baseline, 1h and 3h, respectively), but not in patients with AMI (Fig, 1A). Sex- and age-adjusted linear regression modelling in patients without AMI revealed a significant association of Hb with hs-cTnI (Beta −0.10 [95% CI: −0.14, −0.06]; p<0.001; Fig. 1B). Safety and efficacy of both ESC algorithms were similar in patients with and without anemia; 0/1h (NPV 100.0% [95% CI: 94.7, 100.0]; PPV 52.7% [95% CI: 43.0, 62.3] vs. NPV 99.4% [95% CI: 98.5, 99.8]; PPV 55.7% [95% CI: 50.1, 61.1]); 0/3h (NPV 98.0% [95% CI: 95.3, 99.3]; PPV 48.4% [95% CI: 39.4, 57.5] vs. NPV 97.9 [95% CI: 97.0, 98.6], PPV 59.2 [95% CI: 53.7, 64.6]). During a median follow-up of 1.7 years and after stratification by either ESC algorithm, patients with compared to those without anemia experienced significantly worse outcome for all-cause death (p<0.001; Fig. 1C). In sex-, age- and baseline hs-cTnI-adjusted Cox-regression analysis, anemia was an independent predictor for all-cause death (adjusted hazard ratio [adjHR] 3.6 [95% CI: 2.6, 5.0]), cardiovascular death (adjHR 3.0 [95% CI: 1.8, 5.2]) and rehospitalization (adjHR 1.2 [95% CI: 1.0, 1.5], but not for incidental AMI (adjHR 2.0 [95% CI: 0.8, 4.9]) or revascularization (adjHR 0.8 [95% CI: 0.5, 1.3]). Conclusion Despite the revealed association of Hb and hs-cTnI in the stable setting, the application of the ESC 0/1h and 0/3h algorithms in patients with suspected AMI and concomitant anemia is safe and provides similar efficacy. Patients with anemia experience considerable worse outcome and might therefore benefit from additional diagnostic measures and, potentially, treatment targeting anemia and its cause. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): German Center of Cardiovascular Research (DZHK) and an unrestricted grant by Abbott Diagnostics, Prevencio and Singulex.

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