Publications by authors named "Tomasz Fabiszak"

47 Publications

Assessment of Selected Baseline and Post-PCI Electrocardiographic Parameters as Predictors of Left Ventricular Systolic Dysfunction after a First ST-Segment Elevation Myocardial Infarction.

J Clin Med 2021 Nov 22;10(22). Epub 2021 Nov 22.

Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, ul. Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland.

Objective: To assess the performance of ten electrocardiographic (ECG) parameters regarding the prediction of left ventricular systolic dysfunction (LVSD) after a first ST-segment-elevation myocardial infarction (STEMI).

Methods: We analyzed 249 patients (74.7% males) treated with primary percutaneous coronary intervention (PCI) included into a single-center cohort study. We sought associations between baseline and post-PCI ECG parameters and the presence of LVSD (defined as left ventricular ejection fraction [LVEF] ≤ 40% on echocardiography) 6 months after STEMI.

Results: Patients presenting with LVSD ( = 52) had significantly higher values of heart rate, number of leads with ST-segment elevation and pathological Q-waves, as well as total and maximal ST-segment elevation at baseline and directly after PCI compared with patients without LVSD. They also showed a significantly higher prevalence of anterior STEMI and considerably wider QRS complex after PCI, while QRS duration measurement at baseline showed no significant difference. Additionally, patients presenting with LVSD after 6 months showed markedly more severe ischemia on admission, as assessed with the Sclarovsky-Birnbaum ischemia score, smaller reciprocal ST-segment depression at baseline and less profound ST-segment resolution post PCI. In multivariate regression analysis adjusted for demographic, clinical, biochemical and angiographic variables, anterior location of STEMI (OR 17.78; 95% CI 6.45-48.96; < 0.001), post-PCI QRS duration (OR 1.56; 95% CI 1.22-2.00; < 0.001) expressed per increments of 10 ms and impaired post-PCI flow in the infarct-related artery (IRA; TIMI 3 vs. <3; OR 0.14; 95% CI 0.04-0.46; = 0.001) were identified as independent predictors of LVSD (Nagelkerke's pseudo R for the logistic regression model = 0.462). Similarly, in multiple regression analysis, anterior location of STEMI, wider post-PCI QRS, higher baseline number of pathological Q-waves and a higher baseline Sclarovsky-Birnbaum ischemia score, together with impaired post-PCI flow in the IRA, higher values of body mass index and glucose concentration on admission were independently associated with lower values of LVEF at 6 months (corrected R = 0.448; < 0.00001).

Conclusions: According to our study, baseline and post-PCI ECG parameters are of modest value for the prediction of LVSD occurrence 6 months after a first STEMI.
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http://dx.doi.org/10.3390/jcm10225445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619668PMC
November 2021

Long-term outcome of rotational atherectomy according to burr-to-artery ratio and changes in coronary artery blood flow: Observational analysis.

Cardiol J 2021 Aug 6. Epub 2021 Aug 6.

Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland, Poland.

Background: Rotational atherectomy (RA) has been proven to be efficient for the treatment of calcified and diffuse coronary artery lesions. However, the optimal burr-to-artery ratio (BtAR) remains unidentified as well as an influence of change in blood flow on long-term outcome. Aim of our study was to examine the association between long-term outcome, and both BtAR and change in coronary flow during RA.

Methods: We conducted a retrospective study including patients who underwent RA. Two independent observers calculated BtAR, pre- and postprocedural corrected Thrombolysis in Myocardial Infarction (TIMI) Frame Count (cTFC) for artery treated with RA. The long-term outcome was defined as all-cause mortality.

Results: Receiver operating characteristic (ROC) curve analysis of BtAR determined threshold of 0.6106 for all-cause mortality detection with sensitivity 50.0%, specificity 90.8%, and area under the curve (AUC) 0.730 (p < 0.001). Kaplan-Meier survival analysis showed that the all-cause mortality rate in the group with the BtAR > 0.6106 is significantly higher compared to the patients with lower BtAR (hazard ratio [HR] 3.76, 95% confidence interval [CI] 1.51-9.32; p < 0.001). Kaplan-Meier survival analysis revealed that the all-cause mortality rate in the group with impairment in coronary flow was significantly higher compared to group with cTFC difference ≤ 0 after RA (HR 3.28, 95% CI 1.56-9.31; p = 0.02).

Conclusions: BtAR > 0.6106 is associated with worse prognosis of patients treated with RA. Patients showing post-RA impairment in blood flow in the target artery have worse prognosis.
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http://dx.doi.org/10.5603/CJ.a2021.0082DOI Listing
August 2021

Utilization of Subcutaneous Cardioverter-Defibrillator in Poland and Europe-Comparison of the Results of Multi-Center Registries.

Int J Environ Res Public Health 2021 07 5;18(13). Epub 2021 Jul 5.

Cardiology, Cardiac Arrhythmias Management Department, Clinique Pasteur, 31076 Toulouse, France.

The implantation of a subcutaneous cardioverter-defibrillator (S-ICD) may be used instead of a traditional transvenous system to prevent sudden cardiac death. Our aim was to compare the characteristics of S-ICD patients from the multi-center registry of S-ICD implantations in Poland with the published results of the European Snapshot Survey on S-ICD Implantation (ESSS-SICDI). We compared data of 137 Polish S-ICD patients with 68 patients from the ESSS-SICDI registry. The groups did not differ significantly in terms of sex, prevalence of ischemic cardiomyopathy, concomitant diseases, and the rate of primary prevention indication. Polish patients had more advanced heart failure (New York Heart Association (NYHA) class III: 11.7% vs. 2.9%, NYHA II: 48.9% vs. 29.4%, NYHA I: 39.4% vs. 67.7%, < 0.05 each). Young age (75.9% vs. 50%, < 0.05) and no vascular access (7.3% vs. 0%, < 0.05) were more often indications for S-ICD. The percentage of patients after transvenous system removal due to infections was significantly higher in the Polish group (11% vs. 1.5%, < 0.05). In the European population, S-ICD was more frequently chosen because of patients' active lifestyle and patients' preference (both 10.3% vs. 0%, < 0.05). Our analysis shows that in Poland, compared to other European countries, subcutaneous cardioverters-defibrillators are being implanted in patients at a more advanced stage of chronic heart failure. The most frequent reason for choosing a subcutaneous system instead of a transvenous ICD is the young age of a patient.
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http://dx.doi.org/10.3390/ijerph18137178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297309PMC
July 2021

Diagnostic Performance of Selected Baseline Electrocardiographic Parameters for Prediction of Left Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction.

J Clin Med 2021 May 29;10(11). Epub 2021 May 29.

Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, ul. M. Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland.

To evaluate the diagnostic performance of selected baseline electrocardiographic (ECG) parameters as predictors of left ventricular remodeling (LVR) in patients with a first ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). The study was performed as a single-center cohort study, with 249 patients (74.7% males) included in the final analysis. Nine baseline ECG parameters were evaluated, with respect to occurrence of LVR 6 months after STEMI (defined as an echocardiography-assessed relative >20% increase in end-diastolic left ventricular volume compared with the value at discharge from hospital). The baseline ECG predictors of LVR, identified in univariate analysis, included the number of leads with ST-segment elevation (odds ratio (OR) 1.19, 95% confidence interval (CI) 1.03-1.38, = 0.0212), number of leads with Q-waves (OR 1.21, 95% CI 1.07-1.37, = 0.0033), sum of ST-segment elevation (OR 1.04, 95% CI 1.00-1.08; = 0.0253) and maximal ST-segment elevation (OR 1.14; 95% CI 1.00-1.29; = 0.0446). When added to demographic, clinical and angiographic data, the number of leads with ST-segment elevation (OR 1.17, 95% CI 1.01-1.36; = 0.0413), number of leads with Q-waves (OR 1.15, 95% CI 1.01-1.32; = 0.0354) and the sum of ST-segment elevation (OR 1.04, 95% CI 1.00-1.08; = 0.0331) successfully predicted development of LVR in multivariate logistic regression models. However, after inclusion of biochemical data in multivariate models, none of the electrocardiographic parameters, but increasing body weight, TIMI flow after PCI < 3 and higher maximal values of myocardial necrosis biomarker, was independently associated with the occurrence of LVR 6 months after STEMI. Our study demonstrates modest utility of pre-reperfusion ECG for the prediction of LVR occurrence after six months of STEMI.
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http://dx.doi.org/10.3390/jcm10112405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198269PMC
May 2021

The influence of patient expectations on adherence to treatment regimen after myocardial infarction.

Patient Educ Couns 2021 May 23. Epub 2021 May 23.

Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, M. Curie Skłodowskiej 9 St., 85-094 Bydgoszcz, Poland. Electronic address:

Objective: In-hospital patient education is one of the elements affecting patient adherence to treatment regimen after myocardial infarction (MI). Its effectiveness is determined by educator and patient-dependent factors. Previous studies did not identify patient expectations as an independent determinant of successful education. The aim of this study was to assess whether patient knowledge and expectations affect adherence to treatment regimen in a 1-year follow-up.

Methods: This was a single-center, cohort study with a 1-year follow-up. Patient knowledge and expectations were evaluated using the Readiness for Hospital Discharge after Myocardial Infarction Scale (RHD-MIS scale). Medication adherence (including angiotensin converting enzyme inhibitors (ACEI), P2Y12 receptor inhibitors and statins) was verified based on prescription refill data extracted from The National Health Fund database.

Results: The study included 225 patients aged 30-91 years (mean age 62.9 ± 11.9 years). In the 4th quarter of follow-up, patients with the highest expectations had lower adherence regarding ACEI (p = 0.01), P2Y12 receptor inhibitors (p = 0.03) and the combination of all three analysed medications (p = 0.003).

Conclusions: The initial results suggest presence of a relationship between patient expectations and long-term adherence to treatment.

Practice Implications: Post-MI patient education directed at fulfilling or modification of patient expectations could possibly improve execution of treatment regimen.
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http://dx.doi.org/10.1016/j.pec.2021.05.030DOI Listing
May 2021

Therapy Discontinuation after Myocardial Infarction.

J Clin Med 2020 Dec 19;9(12). Epub 2020 Dec 19.

Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, M. Curie Skłodowskiej 9 St., 85-094 Bydgoszcz, Poland.

The discontinuation of recommended therapy after myocardial infarction predisposes patients to serious thrombotic complications. The aim of this study was a comprehensive analysis of permanent as well as short- and long-term discontinuation of pharmacotherapy, taking into consideration the basic groups of medications and nonadherence determinants in a one-year follow-up in post-myocardial infarction (MI) patients.

Material And Methods: The study was a single center cohort clinical trial with a one-year follow-up including 225 patients (73.3% men, 26.7% women) aged 62.9 ± 11.9 years. In eight cases (3.6%), the follow-up duration was less than one year due to premature death. The following factors were analyzed: lack of post-discharge therapy initiation; short-term therapy discontinuation (<30 days); long-term therapy discontinuation (≥30 days); and permanent cessation of therapy. The analysis of therapy discontinuation was performed based on prescription filling data.

Results: Occupational activity (Odds Ratio (OR) 5.15; 95% Confidence interval (CI) 1.42-18.65; = 0.013) and prior MI (OR 5.02; 95% CI 1.45-16.89; = 0.009) were found to be independent predictors of a lack of post-discharge therapy initiation with P2Y receptor inhibitors. We found no independent predictors of lack of post-discharge therapy initiation with other medications, whether analyzed separately or together. Age above 65 years (Hazard Ratio (HR)-1.59; 95% CI 1.15-2.19; = 0.0049) and prior revascularization (HR-1.44; 95% CI 1.04-2.19; = 0.0273) were identified as independent predictors of therapy discontinuation. Multilogistic regression analysis showed no independent predictors of the cessation of any of the medications as well as the permanent or temporary simultaneous discontinuation of all medications.

Conclusions: The vast majority of post-MI patients discontinue, either temporarily or permanently, one of the essential medications within one year following myocardial infarction. The most likely medication class to be discontinued are statins. Older age and prior cardiac revascularization are independent determinants of therapy discontinuation.
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http://dx.doi.org/10.3390/jcm9124109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766090PMC
December 2020

Low dose of ROSuvastatin in combination with EZEtimibe effectively and permanently reduce low density lipoprotein cholesterol concentration independently of timing of administration (ROSEZE): A randomized, crossover study - preliminary results.

Cardiol J 2021 17;28(1):58-66. Epub 2020 Nov 17.

Department of Cardiology and Internal Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Poland.

Background: In an attempt to improve low density lipoprotein-cholesterol (LDL-C) level control in patients ineffectively treated with statins, we evaluated the effectiveness of a fixed-dose combination (FDC) of 10 mg rosuvastatin and ezetimibe and its relation to the timing of drug administration.

Methods: A randomized, open label, single center, crossover study involving 83 patients with coronary artery disease and hypercholesterolemia with baseline LDL-C ≥ 70 mg/dL. In arm I the FDC drug was administered in the morning for 6 weeks, then in the evening for the following 6 weeks and vice versa in arm II. The primary endpoint was the change in LDL-C after 6 and 12 weeks.

Results: The median LDL-C concentration at baseline, after 6 and 12 weeks respectively was: 98.10 mg/dL (Q1;Q3: 85.10;116.80), 63.14 mg/dL (50.70;77.10) and 59.40 mg/dL (49.00;73.30); p < 0.001. LDL-C levels were similar regardless of the timing of drug administration (morning 62.50 mg/dL [50.70;76.00] vs. evening 59.70 mg/dL [48.20;73.80]; p = 0.259], in both time points: 6 week: 63.15 mg/dL (50.75;80.65) vs. 63.40 mg/dL (50.60;74.00), p = 0.775; and 12 week: 62.00 mg/dL (50.20;74.40) vs. 59.05 mg/dL (47.65;66.05), p = 0.362. The absolute change in LDL-C concentration for the morning vs. evening drug administration was - 6 week: -34.6 mg/dL (-56.55; -19.85) (-34.87%) vs. -31.10 mg/dL (-44.20; -16.00) (-35.87%) (p not significant); 12. week: -34.20 mg/dL (-47.8; -19.0) (-37.12%) vs. -37.20 mg/dL (-65.55; -23.85) (-40.06%) (p not significant). The therapy was safe and well tolerated.

Conclusions: Fixed-dose combination of rosuvastatin and ezetimibe significantly and permanently decreases LDL-C regardless of the timing of drug administration.
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http://dx.doi.org/10.5603/CJ.a2020.0166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105047PMC
September 2021

Prolonged antithrombotic therapy in patients after acute coronary syndrome: A critical appraisal of current European Society of Cardiology guidelines.

Cardiol J 2020 19;27(6):661-676. Epub 2020 Oct 19.

Pavia, Italy.

The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the Dual Antiplatelet Therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor. The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group. Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in post-acute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic therapy (DATT) appear after a longer time from ACS (more than 2 years) and/or from cessation of DAPT (more than 1 year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials.
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http://dx.doi.org/10.5603/CJ.a2020.0132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079117PMC
September 2021

Medication adherence and its determinants in patients after myocardial infarction.

Sci Rep 2020 07 21;10(1):12028. Epub 2020 Jul 21.

Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, Curie Skłodowskiej St. 9, 85-094, Bydgoszcz, Poland.

Non-adherence to prescribed medication is a serious limitation of long-term treatment in patients after myocardial infarction (MI), which can be associated with medical, social and economical consequences. Improvement of medication adherence has been shown to be a challenge for healthcare providers. The aim of this study was to evaluate changes in medication adherence and variability of adherence determinants during follow-up in patients after MI. A single-center, cohort observational study was conducted in 225 post-MI patients treated with primary coronary intervention (PCI) (27% women and 73% men) aged 30-91 years. Adherence was defined as availability of evaluated drugs within 1-year after discharge from hospital, based on completed prescriptions data obtained from the National Health Fund. The analysis of therapeutic plan realization (adherence to medication prescribed at discharge from hospital) embraced only reimbursed drugs: ACEIs (ramipril, perindopril), P2Y12 receptor inhibitors (clopidogrel) and statins (atorvastatin, simvastatin, rosuvastatin). Sufficient adherence was defined as ≥ 80%. During 1-year follow-up, adherence for all three drug classes was 64 ± 25%, with 67 ± 32% for ACEIs, 62 ± 34% for P2Y12 receptor inhibitor and 64 ± 32% for statins. A gradual decline in adherence was observed from 65% ± 26% in the first quarter of follow-up to 51% ± 34% in the last quarter of follow-up (p < 0.00001). Sufficient adherence for all drugs classes was found only in 29% of patients throughout the whole follow-up period (44% for ACEI, 36% for P2Y12 receptor inhibitor and 41% for statins). According to a multivariate analysis, age, prior CABG, level of education, place of residence, economic status and marital status were independent predictors of drug adherence. Whereas patients > 65 years and having a history of prior CABG more often had an insufficient adherence to drugs, married and hypertensive patients, city inhabitants and patients with higher education tended to have a sufficient drug adherence. Adherence to pharmacotherapy after myocardial infarction decreases over time in a similar manner for all pivotal groups of drugs prescribed after MI. A number of socioeconomic and clinical factors have been identified to affect medication adherence over time.
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http://dx.doi.org/10.1038/s41598-020-68915-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374107PMC
July 2020

The impact of readiness to discharge from hospital on adherence to treatment in patients after myocardial infarction.

Cardiol J 2020 Feb 10. Epub 2020 Feb 10.

Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.

Background: The healthcare professionals involved in in-hospital treatment of myocardial infarction (MI) are also responsible to patients for their education before leaving the hospital. This education aims to modify patient behaviour in order to reduce relevant risk factors and improve self-control and adherence to medications. The aim of the study was to analyse the relationship between readiness for discharge from hospital and adherence to treatment at follow-up in MI patients.

Methods: An observational, single-center, MI cohort study with 6-month follow-up was conducted between May 2015 and July 2016. The Readiness for Hospital Discharge after Myocardial Infarction Scale (RHD-MIS) and the Adherence in Chronic Diseases Scale (ACDS) were applied.

Results: Two hundred and thirteen patients aged 30-91 years (62.91 ± 11.26) were enrolled in the study. The RHD-MIS general score ranged from 29 to 69 points (51.16 ± 9.87). A high level of readiness was found in 66 patients (31%), intermediate in 92 (43.2%), and low in 55 (25.8%) of patients. Adherence level assessed with the ACDS 6-months after discharge from hospital ranged from 7 to 28 points (23.34 ± 4.06). An increase in objective assessment of patient knowledge according to RHD-MIS subscale resulted in significantly higher level of adherence at the follow-up visit (p = 0.0154); R Spearman = 0.16671, p = 0.015; p for trend = 0.005. During the 6-month follow-up 3 (1.41%) patients died and 17 (7.98%) were hospitalized for a subsequent acute coronary syndrome.

Conclusions: This study provided preliminary evidence of a long-term association between the results of assessment of readiness for discharge from hospital and adherence to treatment in patients after MI.
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http://dx.doi.org/10.5603/CJ.a2020.0005DOI Listing
February 2020

Transfer Information Assessment in Diagnosis of Vasovagal Syncope Using Transfer Entropy.

Entropy (Basel) 2019 Mar 29;21(4). Epub 2019 Mar 29.

1st Chair and Department of Cardiology, Medical University of Warsaw, 02-097 Warsaw, Poland.

The paper presents an application of Transfer Entropy (TE) to the analysis of information transfer between biosignals (heart rate expressed as R-R intervals (RRI), blood pressure (sBP, dBP) and stroke volume (SV)) measured during head up tilt testing (HUTT) in patients with suspected vasovagal syndrome. The study group comprised of 80 patients who were divided into two groups: the HUTT(+) group consisting of 57 patients who developed syncope during the passive phase of the test and HUTT(-) group consisting of 23 patients who had a negative result of the passive phase and experienced syncope after provocation with nitroglycerin. In both groups the information transfer depends on the phase of the tilt test. In supine position the highest transfer occurred between driver RRI and other components. In upright position it is the driver sBP that plays the crucial role. The pre-syncope phase features the highest information transfer from driver SV to blood pressure components. In each group the comparisons of TE between different phases of HUT test showed significant differences for RRI and SV as drivers.
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http://dx.doi.org/10.3390/e21040347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7514832PMC
March 2019

Determinants of high platelet reactivity in patients with acute coronary syndromes treated with ticagrelor.

Sci Rep 2019 03 8;9(1):3924. Epub 2019 Mar 8.

Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.

High platelet reactivity (HPR) is a risk factor for stent thrombosis, a potentially lethal complication of percutaneous coronary intervention. HPR is also associated with increased risk of myocardial infarction and death in invasively-treated patients with acute coronary syndrome (ACS). HPR occurs even in ACS patients treated with ticagrelor, a state-of-the-art antiplatelet agent, especially during the first hours of treatment. Patient-level pharmacodynamic data obtained from 102 ACS subjects enrolled in two prospective, pharmacodynamic trials were analysed in order to identify clinical features related with increased odds of on-ticagrelor HPR during the first two hours after ticagrelor loading dose in ACS patients. Presence of ST-segment elevation myocardial infarction (versus non-ST-segment elevation ACS) and morphine co-administration were the strongest predictors of HPR at 1 and 2 hours after ticagrelor loading dose according to linear regression analyses, multiple backward stepwise logistic regression analyses and generalized estimating equation model. By pinpointing simple to recognize clinical features, the results of this study facilitate identification of ACS patients who have the highest odds of HPR during the initial phase of treatment with ticagrelor, and who could potentially benefit from alternative treatment strategies.
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http://dx.doi.org/10.1038/s41598-019-40628-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408477PMC
March 2019

Mild therapeutic hypothermia after out-of-hospital cardiac arrest: What does really matter?

Cardiol J 2021 25;28(2):293-301. Epub 2019 Feb 25.

Department of Cardiology and Internal Medicine, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Poland.

Background: Mild therapeutic hypothermia (MTH) is a recommended treatment of comatose patients after out-of-hospital cardiac arrest (OHCA). The aim of the study was to examine determinants of clinical outcome in OHCA survivors treated with MTH and variables associated with MTH induction time.

Methods: Presented herein is an analysis of combined results from a retrospective and a prospective observational study which included 90 OHCA survivors treated with MTH from January 2010 to March 2018. Multivariate regression analysis was performed to determine variables associated with poor neurologic outcome (Cerebral Performance Category 3-5), mortality, and prolonged induction time.

Results: At hospital discharge, 59 (65.6%) patients were alive, of whom 36 (61%) had a good neurologic outcome. Older patients (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.03-1.12) with lower Glasgow Coma Scale (GCS) (OR 0.49, 95% CI 0.30-0.80) were at higher risk of poor neurological outcome. The predictors of in-hospital death included: older age (OR 1.08, 95% CI 1.02-1.13), lower GCS score (OR 0.47, 95% CI 0.25-0.85), presence of cardiogenic shock (OR 3.43, 95% CI 1.11-10.53), and higher doses of adrenaline (OR 1.27, 95% CI 1.04-1.56). Longer induction was associated with shorter cardio-pulmonary resuscitation (CPR) (unstandardized coefficient -3.95, 95% CI -7.09 to -0.81) and lower lactate level (unstandardized coefficient -18.55, 95% CI -36.10 to -1.01).

Conclusions: Unfavorable neurologic outcome in OHCA patients treated with MTH is associated with age and lower GCS score. Risk factors for in-hospital mortality include age, high-dose adrenaline administration, lower GCS score and presence of cardiogenic shock. CPR duration and lactate level were predictive of prolonged MTH induction time.
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http://dx.doi.org/10.5603/CJ.a2019.0023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078942PMC
September 2021

Platelet inhibition with standard vs. lower maintenance dose of ticagrelor early after myocardial infarction (ELECTRA): a randomized, open-label, active-controlled pharmacodynamic and pharmacokinetic study.

Eur Heart J Cardiovasc Pharmacother 2019 07;5(3):139-148

Collegium Medicum, Nicolaus Copernicus University, 13-15 Jagiellońska Street, 85-067 Bydgoszcz, Poland.

Aims: Currently available data indicate that reduction of ticagrelor maintenance dose (MD) 1-3 years after acute myocardial infarction (AMI) not only provides sufficient platelet inhibition but also can improve ticagrelor's safety profile. The aim of this study was to compare the antiplatelet effect of reduced and standard ticagrelor MD in stable patients beginning 1 month after AMI.

Methods And Results: In a single-centre, randomized, open-label, active-controlled trial, on Day 30 following AMI, 52 patients (26 in each study arm) were assigned in a 1:1 ratio to receive either reduced (60 mg b.i.d) or standard (90 mg b.i.d) ticagrelor MD for the following 2 weeks. On Day 45 after AMI the antiplatelet effect of ticagrelor was evaluated with the VASP assay and Multiplate, and there were no significant differences in platelet inhibition between patients on reduced vs. standard MD [VASP: 10.4 (5.6-22.2) vs. 14.1 (9.4-22.1) platelet reactivity index; P = 0.30; Multiplate: 30.0 (24.0-39.0) vs. 26.5 (22.0-35.0) U; P = 0.26]. Likewise, no differences were found regarding the prevalence of on-ticagrelor high platelet reactivity between patients on ticagrelor 60 mg b.i.d vs. 90 mg b.i.d (VASP: 4% vs. 8%; P = 0.67; Multiplate: 15% vs. 8%; P = 0.54). Administration of reduced MD resulted in proportionally lower plasma concentrations of ticagrelor and its active metabolite on Day 45 after AMI.

Conclusion: These results suggest that lowering ticagrelor MD 1 month after AMI confers an adequate antiplatelet effect that is comparable to the standard dose. The tested strategy warrants further research to assess its clinical efficacy and safety.

Clinicaltrials.gov Identifier: NCT03251859.
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http://dx.doi.org/10.1093/ehjcvp/pvz004DOI Listing
July 2019

Entropy Measures in Analysis of Head up Tilt Test Outcome for Diagnosing Vasovagal Syncope.

Entropy (Basel) 2018 Dec 16;20(12). Epub 2018 Dec 16.

1st Department of Cardiology, Medical University of Warsaw, 02-091 Warsaw, Poland.

The paper presents possible applications of entropy measures in analysis of biosignals recorded during head up tilt testing (HUTT) in patients with suspected vasovagal syndrome. The study group comprised 80 patients who developed syncope during HUTT (57 in the passive phase of the test (HUTT(+) group) and 23 who had negative result of passive phase and developed syncope after provocation with nitroglycerine (HUTT(-) group)). The paper focuses on assessment of monitored signals' complexity (heart rate expressed as R-R intervals (RRI), blood pressure (sBP, dBP) and stroke volume (SV)) using various types of entropy measures (Sample Entropy (SE), Fuzzy Entropy (FE), Shannon Entropy (Sh), Conditional Entropy (CE), Permutation Entropy (PE)). Assessment of the complexity of signals in supine position indicated presence of significant differences between HUTT(+) versus HUTT(-) patients only for Conditional Entropy (CE(RRI)). Values of CE(RRI) higher than 0.7 indicate likelihood of a positive result of HUTT already at the passive phase. During tilting, in the pre-syncope phase, significant differences were found for: (SE(sBP), SE(dBP), FE(RRI), FE(sBP), FE(dBP), FE(SV), Sh(sBP), Sh(SV), CE(sBP), CE(dBP)). HUTT(+) patients demonstrated significant changes in signals' complexity more frequently than HUTT(-) patients. When comparing entropy measurements done in the supine position with those during tilting, SV assessed in HUTT(+) patients was the only parameter for which all tested measures of entropy (SE(SV), FE(SV), Sh(SV), CE(SV), PE(SV)) showed significant differences.
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http://dx.doi.org/10.3390/e20120976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7512576PMC
December 2018

Influence of QRS duration and axis on response to cardiac resynchronization therapy in chronic heart failure with reduced left ventricular ejection fraction: A single center study including patients with left bundle branch block.

Cardiol J 2020 16;27(5):575-582. Epub 2018 Nov 16.

Department of Cardiology and Internal Medicine, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, Poland.

Background: The aim of the study was to evaluate QRS duration and axis as predictors of response to cardiac resynchronization therapy (CRT) in order to reduce the proportion of non-responders.

Methods: Retrospective single-center study including 42 CRT recipients, with left bundle branch block (LBBB), left ventricular ejection fraction (LVEF) < 40%, in New York Heart Association (NYHA) class ≥ II. Response to CRT was declared as NYHA class improvement ≥ 1 (symptomatic) and LVEF improvement by ≥ 10% (echocardiographic) > 6 months post implantation.

Results: Symptomatic responders had longer pre- (172.3 ± 17.9 vs. 159.0 ± 18.3 ms; p = 0.027) and postimplantation (157.2 ± 24.1 vs. 136.7 ± 23.2 ms; p = 0.009) QRS duration. Preimplantation QRS < 150 ms predicted poor response (odds ratio [OR] for response vs. lack of response 0.04; 95% confidence interval [CI] 0.001-0.74). Predictors of symptomatic response included: postimplantation QRS > 160 ms (OR 7.2; 95% CI 1.24-41.94), longer QRS duration before (OR for a 1 ms increase 1.04, 95% CI 1.00-1.08) and post implantation (OR for a 1 ms increase 1.04; 95% CI 1.01-1.07). Area under the curve (AUC) for pre- and postimplantation QRS duration was 0.672 (95% CI 0.51-0.84) and 0.727 (95% CI 0.57-0.89), respectively, with cut-off points of 178.5 ms and 157 ms. For post implantation QRS axis, AUC was 0.689 (95% CI 0.53-0.85), with cut-off points of -60.5° or -38.5°. Preimplantation QRS axis was the only predictor of echocardiographic response (OR 0.98; 95% CI 0.96-1.00), with AUC of 0.693 (95% CI 0.54-0.85) and a threshold of -36°.

Conclusions: Marked pre- and postimplantation QRS prolongation and preimplantation negative QRS axis deviation are moderate predictors of response to CRT.
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http://dx.doi.org/10.5603/CJ.a2018.0138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078989PMC
August 2021

The complexity of hemodynamic response to the tilt test with and without nitroglycerine provocation in patients with vasovagal syncope.

Sci Rep 2018 09 28;8(1):14554. Epub 2018 Sep 28.

1st Chair and Department of Cardiology, Medical University of Warsaw, Warsaw, 02-091, Poland.

The paper presents a comparison of vasovagal syndrome occurrence in a head up tilt table test between patients with a positive result of passive tilt test and those with a positive result after pharmacological provocation. The study group consisted of 80 patients: 57 patients who experienced syncope in the passive phase of the test (43 women (aged: 35.6 ± 16.2) and 14 men (aged: 41.7 ± 15.6) and 23 patients who experienced syncope after pharmacological provocation (17 women (age: 32.3 ± 12) and 6 men (age: 43 ± 15). The main investigation was based on the assessment of monitored signals complexity: heart rate, blood pressure and stroke volume. The analysis of complexity in chosen measurement phases was performed with Sample Entropy. The investigation showed that the reactions of autonomic nervous system during tilt test and before syncope are similar for positive result of passive tilt test and positive result of tilt test with provocation. The differences in supine position occurred only in analysis based on impedance measurement (SV: p = 0.01). Significant differences were denoted for all signals just before the syncope (RRI, sBP, dBP: p = 0,00001 and SV: p = 0.01). In analysis of signals complexity the significant differences occurred just before the syncope for Sample Entropy of blood pressure (SampEn (sBP): p = 0.0008, SampEn (dBP): p = 0,0001).
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http://dx.doi.org/10.1038/s41598-018-32718-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162241PMC
September 2018

Assessment of adherence to medication in patients after myocardial infarction treated with percutaneous coronary intervention. Is there a place for newself-reported questionnaires?

Curr Med Res Opin 2019 02 13;35(2):341-349. Epub 2018 Sep 13.

d Department of Cardiology , Medical University of Vienna , Vienna , Austria.

Introduction: Non-adherence to medication regimen after myocardial infarction (MI) leads to increased morbidity and mortality and generates additional cost to the healthcare system.

Objectives: The aim of this systematic review was to critically discuss assessment methods of adherence to medication in patients after myocardial infarction treated with percutaneous coronary intervention and the possible application of a new self-reported questionnaire.

Methods: A systematic investigation of all published literature was conducted to minimize the risk of bias. A database search (PubMed, CENTRAL and Google Scholar databases) from January 1998 through December 2017.

Results: Adequate assessment of patient adherence to treatment is necessary to understand the potential for adverse outcomes. Methods developed for adherence evaluation are classified as subjective and objective or as direct and indirect. Direct, objective measures reflect pharmacokinetics and include measurement of the drug or its metabolite concentration, evaluation of the presence of biological markers given with the drug and direct observation of patients' medication-taking behavior. Several indirect, objective methods are based on evaluation of the availability of prescribed medications assuming that medication is taken exactly as prescribed. Assessment of the effectiveness of treatment, both at the pharmacodynamic and clinical level, indirectly but objectively reflects adherence to treatment. Subjective methods, including patient-kept diaries, patient interviews and self-reported questionnaires, due to their simplicity, real-time feedback and low cost, are often used for adherence evaluation in clinical practice.

Conclusions: In spite of the availability, convenience and variety of methods, measuring adherence still remains a real challenge. Using a well designed questionnaire provides an opportunity to identify patients at increased risk of non-adherence and the obstacles impeding implementation of the treatment plan, allowing implementation of tailored interventions in order to improve patient medication-taking behavior.
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http://dx.doi.org/10.1080/03007995.2018.1510385DOI Listing
February 2019

Adherence to treatment assessed with the Adherence in Chronic Diseases Scale in patients after myocardial infarction.

Patient Prefer Adherence 2018 5;12:333-340. Epub 2018 Mar 5.

Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.

Introduction: A substantial subset of patients after myocardial infarction (MI) discontinue pivotal medication early after discharge. In particular, cessation of antiplatelet treatment may lead to catastrophic ischemic events. Thus, adherence to prescribed medication in patients after MI is an issue of medical and social concern.

Purpose: The aim of the study was to evaluate the level of adherence to treatment using a newly developed scale in patients after MI treated with percutaneous coronary intervention.

Patients And Methods: A single-center, prospective, observational cohort clinical study with a 6-month follow-up was performed. Patients with physical or cognitive impairment, prisoners, soldiers, and family members and coworkers of the researchers were excluded from the study. The impact of selected sociodemographic and clinical factors on adherence was evaluated in 221 patients (63 women and 158 men) aged 30 to 91 years.

Results: The results obtained with the Adherence in Chronic Diseases Scale (ACDS) ranged from 7 to 28 points; with the average and median scored being 23.35 and 24, respectively. The ACDS score reflects the level of adherence to prescribed medication. The high ACDS scores (>26 points) were obtained in 59 (26.7%) patients, intermediate scores (21-26 points) in 110 (49.8%) and low scores (<21 points) in 52 subjects (23.5%). Acute coronary syndrome (re-ACS) occurred in 18 (8.1%) patients during the follow-up period. The high-level adherence (ACDS score >26 points) was found in 11.1% of patients with re-ACS vs 28.4% of the remaining ones (=0.1). Lower scores (mean ± standard deviation) in re-ACS patients were found for items 2 and 3 of the ACDS: 3.11±0.68 vs 3.45±0.73 (=0.02) and 3.28±0.89 vs 3.64±0.64 (=0.04), respectively.

Conclusion: Age and previous MI were found to be independent factors influencing adherence assessed with the ACDS.
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http://dx.doi.org/10.2147/PPA.S150435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842773PMC
March 2018

Rationale and Design of the Effectiveness of LowEr maintenanCe dose of TicagRelor early After myocardial infarction (ELECTRA) pilot study.

Eur Heart J Cardiovasc Pharmacother 2018 07;4(3):152-157

Department of Cardiology, Collegium Medicum, Nicolaus Copernicus University, 9 Skłodowskiej-Curie Street, 85-094 Bydgoszcz, Poland.

Aims: The degree and time course of platelet inhibition using ticagrelor can vary during the acute phase and the following stable period after acute myocardial infarction (AMI). The optimal level of platelet inhibition during the various stages of AMI remains an open question. The aim of the current study is to compare the antiplatelet efficacy of two ticagrelor maintenance dose regimens (60 mg b.i.d. vs. 90 mg b.i.d.) in stable patients following an initial strategy with ticagrelor 90 mg b.i.d. during the first month after AMI.

Methods And Results: The Effectiveness of LowEr maintenanCe dose of TicagRelor early After myocardial infarction (ELECTRA) pilot study is a phase III, single-centre, randomized, open-label, pharmacokinetic/pharmacodynamic trial. The study population will include 50 patients with AMI treated with percutaneous coronary intervention. At Day 30 post-AMI, all trial participants will be randomly assigned in 1:1 ratio to receive either reduced (60 mg b.i.d.) or standard (90 mg b.i.d.) maintenance ticagrelor dose until Day 45 post-AMI. Platelet function testing in each patient will be performed using up to two different methods (the VASP assay and multiple electrode aggregometry). Pharmacokinetics of ticagrelor and its active metabolite (AR-C124910XX) will be assessed by liquid chromatography mass spectrometry.

Conclusion: A de-escalation strategy with reduced dose of ticagrelor (60 mg b.i.d.) following an initial standard dose (90 mg b.i.d.) during the first month after AMI may provide equally effective platelet inhibition as compared to maintenance with the standard ticagrelor dose.

Clinicaltrials. Gov Identifier: NCT03251859.
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http://dx.doi.org/10.1093/ehjcvp/pvx032DOI Listing
July 2018

Impact of levosimendan on platelet function.

Thromb Res 2017 Nov 2;159:76-81. Epub 2017 Oct 2.

Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.

Levosimendan has been developed for treatment of severe heart failure. The favorable hemodynamic effect of levosimendan is related to its unique dual mechanism of action - increase of the contractile force of the myocardium caused by enhanced sensitivity of myofilaments to calcium combined with vasodilatation caused by the opening of adenosine triphosphate - dependent potassium channels. Due to the structural similarities to phosphodiesterase inhibitors it may partly exert its action via inhibition of phosphodiesterase inhibitors III. Inhibition of the phosphodiesterase inhibitors III leads to an increase of intracellular concentration of cyclic adenosine monophosphate causing an anti-aggregatory effect. There are some contradictory or indirect and inconclusive reports related to the impact of levosimendan on platelet function. The aim of this systematic review was to critically discuss the impact of levosimendan on platelet function according to currently available knowledge based on the findings of experimental as well as observational and randomized clinical studies.
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http://dx.doi.org/10.1016/j.thromres.2017.10.001DOI Listing
November 2017

Establishing reference intervals for galectin-3 concentrations in serum requires careful consideration of its biological determinants.

Clin Biochem 2017 Jul 18;50(10-11):599-604. Epub 2017 Mar 18.

Department of Laboratory Medicine, Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Poland.

Background: Appropriately established reference intervals for laboratory biomarkers may help the interpretation of their results and facilitate clinical utilization.

Objectives: i) To determine reference intervals for serum galectin-3 measured using the Architect STAT immunoassay, and ii) to identify factors affecting galectin-3 concentrations.

Methods: We recruited 533 questionnaire-identified apparently healthy individuals, in which laboratory biomarkers were used to detect asymptomatic myocardial injury and dysfunction, ongoing inflammation, hyperglycemia, dyslipidemia, and renal dysfunction. A final reference group of 180 subjects was selected.

Results: 2.5th and 97.5th percentiles of distribution of galectin-3 concentrations in the reference group (90% confidence interval) were 5.9 (5.0-6.8) and 18.1 (17.2-19.0) μg/L, respectively. Older age contributed to higher galectin-3 concentrations, but influenced derived reference intervals to a lesser extent. Other major determinants of galectin-3 concentrations observed in the questionnaire-screened population were not linked to galectin-3 in reference individuals. In aiming to decide if reference limits should be partitioned by age, we compared galectin-3 concentrations in subjects <40 (n=124) and ≥40years (n=56). Higher galectin-3 concentrations were found in older people (median, 12.4μg/L vs. 11.5μg/L, p=0.016). Accounting for manufacturer's declared imprecision at galectin-3 physiological concentrations of <10% (as CV) and the estimated URL for subjects ≥40 (18.8μg/L) and <40 (17.9μg/L), we recommend the adoption of a single URL for the overall adult population.

Conclusions: We established reference intervals for galectin-3 in which the effects of biological determinants were irrelevant. Although in healthy subjects age may affect galectin-3 release, this does not appear to necessitate age-related reference limits.
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http://dx.doi.org/10.1016/j.clinbiochem.2017.03.015DOI Listing
July 2017

Crushed sublingual versus oral ticagrelor administration strategies in patients with unstable angina. A pharmacokinetic/pharmacodynamic study.

Thromb Haemost 2017 04 16;117(4):718-726. Epub 2017 Feb 16.

Piotr Niezgoda, MD, Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland, Tel.: +48 52 5854023, Fax: +48 52 5854024, E-mail:

Oral administration of crushed ticagrelor tablets turned out to be an efficacious method that improves its pharmacokinetics and pharmacodynamics. This strategy, however, is unlikely to eliminate the drug-drug interaction in patients receiving intravenous morphine, as the impairment of the P2Y12 inhibitor absorption related to decreased propulsive motility of the gastro-intestinal tract is the most likely mechanism of interaction. Thus, we designed a pharmacokinetic and pharmacodynamic study setting the feasibility of platelet inhibition with a loading dose of ticagrelor given as crushed tablets sublingually compared with two other ticagrelor loading dose administration strategies: integral tablet given orally and crushed tablet given orally in patients with unstable angina. Ticagrelor and its metabolite AR-C124900XX plasma concentration was evaluated in nine time points (time frame of 6 hours) using liquid chromatography coupled with mass spectrometry; platelet reactivity was evaluated using multiple electrode aggregometry. The area under the plasma concentration-time curve for ticagrelor and AR-C124900XX was significantly higher in patients treated with crushed tablets given orally compared with crushed tablets given sublingually only within the first hour after loading dose (936.9 ± 898.0 vs 368.0 ± 422.4, p=0.042 and 103.4 ± 120.8 vs 31.3 ± 43.9, p=0.031, respectively). Moreover, we showed significantly stronger platelet inhibition in patients receiving crushed ticagrelor orally vs. sublingually at 30 and 45 min after the loading dose (p=0.024 and p=0.016, respectively). Therefore, the administration strategy of ticagrelor determines the pharmacokinetic and pharmacodynamic profile of both ticagrelor and its active metabolite AR-C124900XX.
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http://dx.doi.org/10.1160/TH16-08-0670DOI Listing
April 2017

Impact of lipid markers and high-sensitivity C-reactive protein on the value of the 99th percentile upper reference limit for high-sensitivity cardiac troponin I.

Clin Chim Acta 2016 Nov 28;462:193-200. Epub 2016 Sep 28.

Department of Laboratory Medicine, Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Poland.

Objectives: i) To assess the relationship between lipid markers and high-sensitivity C-reactive protein (hs-CRP), and high-sensitivity cardiac troponin I (hs-cTnI) in the reference population, and ii) to evaluate the impact of lipid markers and hs-CRP on the 99th percentile upper reference limit (URL) for hs-cTnI.

Methods: 531 questionnaire-identified presumably healthy individuals were enrolled in a single-center, cross-sectional study. Surrogate biomarkers for diabetes, myocardial and renal dysfunction were used to refine the healthy cohort (n=408). Lipid profile, total cholesterol:high-density lipoprotein cholesterol (HDL-C) ratio, non-HDL-C, apolipoprotein AI (apoAI), apolipoprotein B (apoB), apoB:apoAI ratio, lipoprotein(a), small dense low-density lipoprotein cholesterol (LDL-C) and hs-CRP were determined.

Results: Individuals with detectable vs. non-detectable hs-cTnI concentrations more often showed elevated LDL-C (60% vs. 46%; p=0.002), apoB (73% vs. 61%; p=0.008), apoB:apoAI ratio (53% vs. 40%; p=0.005) and lipoprotein(a) (15% vs. 7%; p=0.015). The apoB:apoAI ratio and to a lesser extent other lipid markers, but not hs-CRP, were positively associated with hs-cTnI concentration in univariate and multivariate analyses. Exclusion of individuals with elevated apoB:apoAI ratio or apoB, but not hs-CRP, lowered the 99th percentile URL in the healthy cohort respectively by 12.9% (6.2 vs. 5.4ng/L) and 14.5% (6.2 vs. 5.3ng/L). The corresponding reduction for both lipid biomarkers in the presumably healthy population was 24.0% (7.5 vs. 5.7ng/L).

Conclusion: Our study demonstrates that atherogenic lipid markers, particularly apoB:apoAI ratio or apoB, influence the 99th percentile URL for hs-cTnI.
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http://dx.doi.org/10.1016/j.cca.2016.09.020DOI Listing
November 2016

Which platelet function test best reflects the in vivo plasma concentrations of ticagrelor and its active metabolite? The HARMONIC study.

Thromb Haemost 2016 Nov 15;116(6):1140-1149. Epub 2016 Sep 15.

Marek Koziński, Department of Principles of Clinical Medicine, Collegium Medicum, Nicolaus Copernicus University, 9 Skłodowskiej-Curie Street, Bydgoszcz 85-094, Poland, Tel.: +48 52 5854023, Fax: +48 52 5854024, E-mail:

Aim of this study was assessment of the relationship between concentrations of ticagrelor and its active metabolite (AR-C124910XX) and results of selected platelet function tests. In a single-centre, cohort study, patients with myocardial infarction underwent blood sampling following a 180 mg ticagrelor loading dose intake (predose, 1, 2, 3, 4, 6, 12, 24 hours postdose) to perform pharmacokinetic and pharmacodynamic assessments. Platelet reactivity was evaluated using the VASP-assay, the VerifyNow device and the Multiplate analyzer. Analysis of 36 patients revealed high negative correlations between ticagrelor concentrations and platelet reactivity evaluated with all three platelet function tests (the VASP-assay: RS=-0.722; p<0.0001; the VerifyNow device: RS=-0.715; p<0.0001; the Multiplate analyzer: RS=-0.722; p<0.0001), with no significant differences between correlation coefficients. Similar results were found for AR-C124910XX. Platelet reactivity values assessed with all three methods generally correlated well with each other; however, a significantly higher correlation (p<0.02) was demonstrated between the VerifyNow and Multiplate tests (RS=0.707; p<0.0001) than in other assay combinations (the VASP-assay and the VerifyNow device: RS=0.595; p<0.0001; the VASP-assay and the Multiplate analyzer: RS=0.588; p<0.0001). With respect to the recognition of high platelet reactivity, we found higher measurement concordance between the VerifyNow and Multiplate tests compared with other assay combinations, while for low platelet reactivity, only results of the VerifyNow and Multiplate assay were related to each other. Platelet reactivity measurements performed with the VASP, VerifyNow and Multiplate tests show comparably strong negative correlations with ticagrelor and AR-C124910XX concentrations.
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http://dx.doi.org/10.1160/TH16-07-0535DOI Listing
November 2016

Impact of morphine on antiplatelet effects of oral P2Y12 receptor inhibitors.

Int J Cardiol 2016 Jul 17;215:201-8. Epub 2016 Apr 17.

Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Fairfax, VA, USA.

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http://dx.doi.org/10.1016/j.ijcard.2016.04.077DOI Listing
July 2016

Adherence to antiplatelet treatment with P2Y12 receptor inhibitors. Is there anything we can do to improve it? A systematic review of randomized trials.

Curr Med Res Opin 2016 08 25;32(8):1441-51. Epub 2016 May 25.

b Department of Cardiology and Internal Medicine, Collegium Medicum , Nicolaus Copernicus University , Bydgoszcz , Poland.

Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndromes (ACS) and/or undergoing percutaneous coronary interventions. Non-adherence to medication after ACS may lead to increased morbidity, mortality, and costs to the healthcare system due to elevated risk of stent thrombosis, myocardial infarction or death. Medication adherence is an issue of growing concern regarding the improvement of health system performance. Promoting medication adherence offers a rare opportunity to simultaneously improve health outcomes while reducing costs of treatment in patients with coronary artery disease (CAD). The aim of this systematic review was to critically discuss adherence to antiplatelet treatment with P2Y12 receptor inhibitors in CAD patients. After a systematic investigation of the literature in databases including PubMed, CENTRAL and Google Scholar, using appropriate keywords, and considering clinical randomized, prospective observational and retrospective studies, reporting on adherence to treatment with inhibitors of P2Y12 platelet receptors or educational interventions aimed to improve medication adherence in patients with CAD, seven articles were considered eligible for inclusion in this systematic review. Reported adherence to clopidogrel, despite catastrophic consequences of its premature discontinuation, is low. We identified several determinants of low adherence and early discontinuation of clopidogrel. We also present data on the usefulness, utilization and credibility of different methods of medication adherence assessment, and suggest and critically discuss available interventions aimed at improvement of adherence to clopidogrel, still showing the need for innovative approaches to achieve enhanced medication adherence and improve health outcomes after acute myocardial infarction.
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http://dx.doi.org/10.1080/03007995.2016.1182901DOI Listing
August 2016

Discrepancies in assessment of adherence to antiplatelet treatment after myocardial infarction.

Pharmacology 2015 15;95(1-2):50-8. Epub 2015 Jan 15.

Department of Health Promotion, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.

The poor response to clopidogrel is multifactorial and includes, amongst others, low patient adherence to medication. The aim of this study was to assess the reported patient adherence to treatment with clopidogrel and confront it with adherence assessed by drug availability. We evaluated determinants of adherence and its impact on platelet aggregation and clinical outcome. The study population comprised 184 patients treated with primary percutaneous coronary intervention for acute myocardial infarction. Follow-up visits were scheduled at 3, 6 and 9 months after discharge. Patient adherence to clopidogrel was defined according to self-reported drug intake and verified based on data from the National Health Fund regarding the purchase of prescribed drugs. The patients were judged as adherent when the proportion of drug availability exceeded 80%. According to drug availability, 100 (54.3%) patients were adherent and 84 (45.7%) were nonadherent. The analysis identified the following factors as predictors of low adherence (<80%): adenosine diphosphate-induced platelet aggregation (ADP-PA) during hospitalization ≤45 U, male gender and occurrence of ST-elevation myocardial infarction [(STEMI) vs. non-STEMI (NSTEMI)], while three-vessel disease was predictive of high adherence to medication. Compared with drug availability-based assessment, self-reported drug intake was significantly different: 172 (94.5%) patients reported regular and 10 (5.5%) patients reported irregular intake of clopidogrel. Clinical follow-up suggested that the self-reported nonregular clopidogrel intake may discriminate patients with a high risk of cardiovascular events. We demonstrated a huge discrepancy between the two most widely used methods for the evaluation of adherence to clopidogrel in secondary prevention treatment in patients after STEMI and NSTEMI. ADP-PA during hospitalization ≤45 U, male gender and STEMI (vs. NSTEMI) were independent predictors of nonadherence while three-vessel disease was independently predictive of adherence to treatment with clopidogrel in the investigated population.
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http://dx.doi.org/10.1159/000371392DOI Listing
October 2015

Influence of cardiac resynchronization therapy on oxidative stress markers in patients with chronic heart failure.

Cardiol J 2014 8;21(5):576-82. Epub 2014 Jul 8.

Department of Cardiology and Inter nal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.

Background: The aim of the study was to assess changes of substances of oxidative stress in patients treated with cardiac resynchronization therapy (CRT).

Methods: The study comprised 51 patients with median age of 66 years. The presence, severity, and changes of oxidative stress during CRT were assessed and expressed as malondialdehyde (MDA) concentration in plasma or in red blood cells. Antioxidant activity was assessed by the activity of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in red blood cells. The concentration and activities were analyzed directly prior to implantation, 2-5 days after the procedure and after 6 months. Follow-up (6 months) included clinical, echocardiographic and implanted device assessments.

Results: During the follow-up, 14% patients died. The median percentage of biventricular pacing was 99.29%. After 6 months 88% of patients improved NYHA, 12% remained as non-responders. Left ventricular ejection fraction increased from median 21.5% to 29% (p < 0.05). Left ventricular end-diastolic diameter decreased significantly from a median of 69.5 mm to 63 mm (p < 0.05). After a 6-month study, MDA plasma concentration and the activity levels of each antioxidant enzymes (CAT, SOD, GPx) showed a statistically significant reduction (p < 0.05). Changes concerning MDA concentrations in red blood cells remained statistically insignificant.

Conclusions: Resynchronization effect oxidative stress by reducing plasma concentration of MDA, CAT, SOD and GPX.
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http://dx.doi.org/10.5603/CJ.a2014.0051DOI Listing
January 2016
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