21 research outputs found

    Multimarker approach with cystatin C, N-terminal pro-brain natriuretic peptide, C-reactive protein and red blood cell distribution width in risk stratification of patients with acute coronary syndromes

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    INTRODUCTION AND AIM: Biomarkers have emerged as interesting predictors of risk in patients with acute coronary syndromes (ACS). The aim of this study was to determine the utility of the combined measurement of cystatin C (CysC), C-reactive protein (CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and red blood cell distribution width (RDW) in the risk stratification of patients with ACS. METHODS: In this prospective study including 682 patients consecutively admitted to a coronary care unit for ACS, baseline measurements of CysC, CRP, NT-proBNP and RDW were performed. Patients were categorized on the basis of the number of elevated biomarkers at presentation. The primary outcome was 6-month mortality. RESULTS: The number of biomarkers elevated on admission (study score) was an independent predictor of 6-month mortality; patients with four biomarkers elevated on admission had a significantly higher risk of 6-month mortality compared with patients with none or one. In addition, in patients with high risk defined by the GRACE score, our multimarker score was able to further categorize their risk of 6-month mortality. CONCLUSIONS: A multimarker approach using CysC, NT-proBNP, CRP and RDW was an independent predictor of 6-month mortality and added prognostic information to the GRACE risk score in patients with ACS and high risk defined by GRACE, with increasing mortality in patients with a higher number of elevated biomarkers on admission

    Biomarkers for the diagnosis and management of heart failure

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    Heart failure (HF) is a significant cause of morbidity and mortality worldwide. Circulating biomarkers reflecting pathophysiological pathways involved in HF development and progression may assist clinicians in early diagnosis and management of HF patients. Natriuretic peptides (NPs) are cardioprotective hormones released by cardiomyocytes in response to pressure or volume overload. The roles of B-type NP (BNP) and N-terminal pro-B-type NP (NT-proBNP) for diagnosis and risk stratification in HF have been extensively demonstrated, and these biomarkers are emerging tools for population screening and as guides to the start of treatment in subclinical HF. On the contrary, conflicting evidence exists on the role of NPs as a guide to HF therapy. Among the other biomarkers, high-sensitivity troponins and soluble suppression of tumorigenesis-2 are the most promising biomarkers for risk stratification, with independent value to NPs. Other biomarkers evaluated as predictors of adverse outcome are galectin-3, growth differentiation factor 15, mid-regional pro-adrenomedullin, and makers of renal dysfunction. Multi-marker scores and genomic, transcriptomic, proteomic, and metabolomic analyses could further refine HF management

    Lack of prognostic significance for major adverse cardiac events of soluble suppression of tumorigenicity 2 levels in patients with ST-segment elevation myocardial infarction

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    Background: Elevation of soluble suppression of tumorigenicity 2 (sST2) is associated with cardiac fibrosis and hypertrophy. Under investigation herein, was whether sST2 level is associated with major adverse cardiac events (MACE) and left ventricular (LV) remodeling after primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: In total, this study included 184 patients who underwent successful primary PCI. A subsequent guideline-based medical follow-up was included (61.4 ± 11.8 years old, 85% male, 21% with Killip class ≥ I). sST2 concentration correlations with echocardiographic, angiographic, laboratory parameters, and clinical outcomes in STEMI patients were evaluated. Results: The median sST2 level was 60.3 ng/mL; 6 (3.2%) deaths occurred within 1 year. The sST2 level correlated with LV ejection fraction (LVEF) changes from baseline to 6 months (r= –0.273; p = 0.006) after adjustment for echocardiographic parameters including wall motions score index (WMSI). Recovery of LVEF at 6 months was highest in the tertile 1 group (Δ6 months – baseline LVEF; tertile 1, p = 0.001; tertile 2, p = 0.319; tertile 3, p = 0.205). The decrease in WMSI at 6 months was greater in the tertiles 1 and 2 groups than in the tertile 3 group (Δ6 months – baseline WMSI; tertile 1, p = 0.001; tertile 2, p = 0.013; tertile 3, p = 0.055). There was no association between sST2 levels and short-term (log rank p = 0.598) and long-term (p = 0.596) MACE. Conclusions: sST2 concentration have predictive value for LV remodeling on echocardiography in patients with STEMI who underwent primary PCI. However, sST2 concentration was not associated with short-term and long-term MACE

    Prognostication in acute heart failure and cardiogenic shock : focus on electrocardiography and biomarkers

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    Acute heart failure (AHF) is a leading cause of hospitalizations in patients over the age of 65 worldwide, and is associated with high mortality. Cardiogenic shock (CS), the most severe form of AHF, is characterized by hypotension and end-organ hypoperfusion. Acute coronary syndrome (ACS) precipitates a third of all cases of AHF, and up to 80% of CS. Objective and timely risk assessment in AHF is challenging due to the heterogeneity in its pathophysiology and clinical picture. Risk assessment has traditionally relied on clinical parameters, which may remain subjective or become evident too late, after end-organ dysfunction has become irreversible. Considering the costs and possible adverse effects, application of the most aggressive therapies should be limited to those that most likely procure benefit. The aim of this thesis is to evaluate the prognostic value of electrocardiographic changes and biomarkers in AHF and CS. The patient data come from three cohorts of AHF and two cohorts of CS. All cohorts are independent, prospective, observational, investigator-initiated European cohorts. Study I compared the prognostic value of ventricular conduction blocks (VCB) in patients with new-onset (de novo) AHF and in patients with acutely decompensated chronic heart failure (ADCHF). Study II investigated the role of VCBs in ACS-related CS. Half the patients had a VCB in their baseline ECG, and the presence of any VCB predicted mortality independently of baseline clinical variables or angiographic findings. Studies III-IV investigated the role of two novel biomarkers, sST2 and bio-ADM, in cariogenic shock. Study III showed that sST2 provide strong and complementary prognostic value to NT-proBNP in ACS-related CS, and can help in stratification of patients into low, intermediate and high-risk groups as early as 12 hours after detection of shock. Study IV evaluated in CS patients the prognostic value and association with haemodynamic parameters of bio-ADM compared to lactate. Whereas lactate had good prognostic value in the early phase, its levels normalized during the first 24 hours in the majority of patients, with a decreasing prognostic value thereafter. In contrast, levels of bio-ADM stayed elevated in non-survivors during the first 4 days of intensive care, and bio-ADM had good prognostic value when measured on days 2 to 4. In conclusion, in patients with AHF or CS, electrocardiographic alterations may prove useful in early risk assessment on top of clinical parameters. In addition, biomarkers provide a novel approach in CS risk assessment.Akuutti sydämen vajaatoiminta on yksi yleisimmistä sairaalahoitoon johtavista sairauksista, ja siihen liittyy merkittävä kuolleisuus. Sydänperäinen sokki on akuutin vajaatoiminnan vaikein muoto; sille on tunnusomaista matala verenpaine ja yleinen elimistön verenkierron vajaus. Sepelvaltimotautikohtaus on akuutin vajaatoiminnan taustalla noin kolmasosassa tapauksista, mutta jopa 80 %:ssa tapauksista sydänperäisessä sokissa. Johtuen akuutin vajaatoiminnan kliinisen kuvan ja taustalla vaikuttavien patofysiologisten mekanismien moninaisuudesta objektiivinen ja oikea-aikainen riskinarvio on haastavaa. Varhainen riskinarvio on kuitenkin tärkeää hoitomuotojen valintaa ja ajoitusta ajatellen erityisesti sokkipotilailla. Perinteisesti riskinarvio on perustunut kliinisiin löydöksiin, joiden tulkinnassa voi kuitenkin olla subjektiivisuutta ja ne voivat ilmetä sairauden liian myöhäisessä vaiheessa, kun peruuttamattomia elinvaurioita on jo ehtinyt kehittyä. Huomioiden raskaimpien hoitomuotojen, kuten sydämen apupumppujen, korkea komplikaatioriski ja hinta, niiden käyttö tulisi rajata potilaille jotka todennäköisimmin niistä hyötyvät. Tämän väitöskirjatyön tavoitteena on määrittää sydänsähkökäyrä (EKG) –muutosten sekä uusien biomerkkiaineiden ennustearvo akuutissa sydämen vajaatoiminnassa ja sydänperäisessä sokissa. Väitöskirjatyön potilasmateriaali on peräisin kolmesta akuutin sydämen vajaatoiminnan sekä kahdesta sydänperäisen sokin potilaskohortista. Kaikki aineistot ovat eteneviä, havainnoivia, tutkijalähtöisiä eurooppalaisia potilasaineistoja. Osatyössä I tutkittiin EKG:ssa nähtävien kammiojohtumishäiriöiden yhteyttä kuolleisuuteen potilailla joilla akuutti vajaatoiminta ilmeni ensimmäistä kertaa (de novo) verrattuna potilaisiin joilla oli kroonisen sydämen vajaatoiminnan pahenemisvaihe. Osatyössä II tutkittiin kammiojohtumishäiriöitä äkillisestä sepelvaltimokohtauksesta johtuvassa sydänperäisessä sokissa. Puolella potilaista alkuvaiheen EKG:ssa oli jokin kammiojohtumishäiriö, ja kammiojohtumishäiriöt ennustivat suurempaa kuolleisuutta kliinisistä piirteistä ja sepelvaltimotaudin vaikeusasteesta riippumatta. Osatöissä III ja IV tutkittiin kahden uuden biomerkkiaineen, sST2:n ja bio-ADM:n, ennustearvoa kardiogeenisessä sokissa. Osatyö III osoitti, että sST2:lla ja NT-proBNP:llä on vahva itsenäinen ja toisiaan tukeva ennustearvo sydänperäisessä sokissa, ja niiden yhteismäärityksellä potilaat voidaan jakaa matalan, keskisuuren ja suuren riskin ryhmiin jo 12 tuntia sokin toteamisesta. Osatyö IV määritti bio-ADM:n ennustearvoa sekä yhteyttä hemodynaamisiin muuttujiin verrattuna laktaattiin sydänperäisessä sokissa. Laktaatilla oli hyvä ennustearvo ensimmäisten 24 tunnin aikana sokin toteamisesta, mutta sen pitoisuus normaalistui valtaosalla potilaista 24 tunnissa ja sen ennustearvo väheni sen jälkeen. Korkea bio-ADM pitoisuus heijasti matalaa verenpainetta ja sydämen minuuttivoluumia sekä korkeaa keskuslaskimo- ja keuhkovaltimopainetta, ja bio-ADM:n ennustearvo oli parhaimmillaan kun se mitattiin 2.-4. päivänä sokin toteamisesta. Yhteenvetona voidaan todeta, että EKG-muutoksia voidaan hyödyntää kliinisten muutosten rinnalla varhaisessa riskinarviossa akuuttia sydämen vajaatoimintaa tai sydänperäistä sokkia sairastavilla potilailla. Lisäksi uudet biomerkkiaineet mahdollistavat täysin uuden lähestymistavan sydänperäisen sokin riskinarviossa

    Novel Biomarkers for Heart Disease

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    Cardiac biomarkers such as troponins and natiuretic peptides have made a great impact on clinical decision making as well as improving our understanding of molecular mechanisms of different disease conditions. However, the biomarkers that are currently in use do not reflect all the multiple disease pathways that are involved in a broad spectrum of cardiac disease conditions ranging from acute coronary syndrome, to heart failure (and heart failure with preserved ejection fraction, HFpEF), to pulmonary hypertension or arrhythmias. In this Special Issue, we will provide an overview of the current developments in the field of biomarker research, beginning with research on molecular pathways and cellular communication (e.g., microRNA) up to the clinical use of biomarkers

    Biomarkers of neurohormonal activation, on-going myocardial damage, haemostasis and inflammation in patients with stable chronic heart failure due to left ventricular systolic dysfunction and potential novel treatment

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    The prognosis of patients with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD) remains poor despite the progress in modern therapy. Btype natriuretic peptide (BNP) is a useful diagnostic and most consistent prognostic markers in CHF. However, treatment strategy guided by natriuretic peptides does not necessarily improve the outcome. In addition to myocardial remodelling, CHF is a systemic syndrome involving neurohormonal activation, inflammatory up-regulation, endothelial dysfunction and haemopoietic, haemostatic and haemorrheologic disturbance. In patients with CHF, the projects of this thesis investigated the potential prognostic role of some biomarkers which reflect these pathophysiological processes in addition to NT-proBNP.The haemostatic markers investigated were D-dimer and fibrinogen for thrombogenesis; t-plasminogen activator and plasminogen activator inhibitor-1 for fibrinolysis, von Willebrand factor activity and soluble E-selectin for endothelial function, and soluble P-selectin for platelet activity. The role of white and red cell variables from routine full blood count was also explored. Heart-type fatty acid-binding protein (H-FABP), a sensitive marker for myocardial injury, was used as a marker for on-going myocardial damage/remodelling. The change in the level of these markers with time for dynamic risk stratification was also explored.Coronary artery disease (CAD) is the commonest cause of CHF and conventional invasive revascularisation has not been proven to improve the prognosis of the patients. Enhanced external counterpulsation (EECP) has been shown to improved myocardial perfusion mainly in patients with CAD. Building on the experience from studies of patients with angina, potential role of EECP in improving myocardial function and perfusion in patients with LVSD and CAD was investigated. Its effects on some biomarkers were also investigated.These studies confirmed the potential prognostic value of a few laboratory markers including H-FABP; whilst showing that EECP can improve regional myocardial function and perfusion with a short-term reduction in H-FABP
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