The Effect of Intracoronary Infusion of Autologous Bone Marrow-Derived Lineage-Negative Stem/Progenitor Cells on Remodeling of Post-Infarcted Heart in Patient with Acute Myocardial Infarction.

Introduction: Regenerative capacity of the heart is limited, and the post-infarct left ventricle (LV) dysfunction is associated with poor prognosis. Administration of stem/progenitor cells (SPCs) is a promising approach for cardiac regeneration. Objectives: In the study, we assessed LV function and post-infarcted remodeling in patients with ST-elevated myocardial infarct (STEMI) who received autologous lineage-negative (LIN-) SPCs. Patients and methods: Patients with STEMI and one-vessel coronary artery disease treated with percutaneous revascularisation were divided into study group (LIN- group, 15 patients) that received standard therapy and autologous BM-derived LIN- SPCs and control group (standard therapy group, 19 patients). The cells were administered intracoronary 24 hours after STEMI. The follow-up was 12 months with subsequent non-invasive tests and laboratory parameter evaluation on days 1st, 3rd, and 7th as well as at 1st, 3rd, 6th and 12th month after STEMI. Results: All procedures related to SPCs administration were well tolerated by the patients. In 12-month follow-up, there were no major adverse cardiac events connected with LIN- SPCs administration. During 12-month follow-up, 9 patients from LIN- group (Responders) achieved an improvement in LV ejection fraction (>10% after 12 months) with no signs of unfavorable LV remodeling. Laboratory parameters analysis showed that Troponin T levels were significantly lower until day 7th in the Responders group, while brain natriuretic peptide (BNP) level remained significantly lower from day 3rd to 12th month respectively. Conclusions: Intracoronary infusion of autologous BM-derived LIN- stem/progenitor cells is feasible and safe for patient. Improvement in LV function and prevention of unfavorable remodeling in the 60% of study group seems relatively promising. Stem cell-based therapy for cardiac regeneration still needs more accurate and extensive investigations to estimate and improve their efficacy.

Novel Evidence of the Increase in Angiogenic Factor Plasma Levels after Lineage-Negative Stem/Progenitor Cell Intracoronary Infusion in Patients with Acute Myocardial Infarction.

Cell therapy raises hope to reduce the harmful effects of acute myocardial ischemia. Stem and progenitor cells (SPCs) may be a valuable source of trophic factors. In this study, we assessed the plasma levels of selected trophic factors in patients undergoing application of autologous bone marrow (BM)-derived, lineage-negative (Lin-) stem/progenitor cells into the coronary artery in the acute phase of myocardial infarction. The study group consisted of 15 patients with acute myocardial infarction (AMI) who underwent percutaneous revascularization and, afterwards, Lin- stem/progenitor cell administration into the infarct-related artery. The control group consisted of 19 patients. BM Lin- cells were isolated using immunomagnetic methods. Peripheral blood was collected on day 0, 2, 4, and 7 and after the first and third month to assess the concentration of selected trophic factors using multiplex fluorescent bead-based immunoassays. We found in the Lin- group that several angiogenic trophic factors (vascular endothelial growth factor, Angiopoietin-1, basic fibroblast growth factor, platelet-derived growth factor-aa) plasma level significantly increased to the 4th day after myocardial infarction. In parallel, we noticed a tendency where the plasma levels of the brain-derived neurotrophic factor were increased in the Lin- group. The obtained results suggest that the administered SPCs may be a valuable source of angiogenic trophic factors for damaged myocardium, although this observation requires further in-depth studies.

Angiographic severity of coronary artery disease and cardiovascular risk in acute coronary syndrome in patients with metabolic syndrome.

BACKGROUND: The extent of angiographic lesions, size of infarct, and in-hospital and long-term prognosis in patients with metabolic syndrome (MS) have not been clearly determined. AIM: The aim of the study was to investigate the effect of MS on the severity of coronary artery disease (CAD) and cardio-vascular risk evaluated using the GRACE 2.0 risk score and left ventricular ejection fraction (LVEF) in patients with first acute coronary syndrome (ACS) treated with coronary angioplasty. METHODS: The study was conducted in a group of 160 consecutive patients hospitalised for their first ACS. Coronary angiogra-phy was assessed and an echocardiographic evaluation of LVEF was performed. MS was diagnosed according to the National Cholesterol Education Programme-Adult Treatment Panel III criteria. Cardiovascular risk was evaluated using the GRACE 2.0 score. Statistical analysis was performed using the STATISTICA software version 12.0. RESULTS: Diagnostic criteria for MS were met by 53.5% of the patients. Patients with and without MS did not differ in angio-graphic severity of CAD and cardiovascular risk as evaluated with the GRACE 2.0 score. LVEF was significantly elevated in patients with MS. In the examined group the angiographic severity of CAD correlated positively with age, body mass index (BMI) and the homeostatic model assessment for insulin resistance (HOMA-IR) index. The cardiovascular risk correlated positively with age, BMI, fasting insulin levels, and HOMA-IR, and inversely with blood pressure and triglyceride levels. The multivariable regression model for predicting the LVEF value indicated that the strongest prognostic factor was the type of ACS. CONCLUSIONS: The associations between the angiographic severity of CAD and age, BMI, and insulin resistance (IR) confirm the involvement of these parameters in coronary atherosclerosis. The correlations between the estimated cardiovascular risk and IR indicate the prognostic value of metabolic parameters in patients after first ACS. The type of ACS is the strongest predictor of LVEF at discharge in this population.

The paradox of the first cycle of chemotherapy-transient improvement of contractility and diastolic function after the first cycle of anthracycline-based chemotherapy: a prospective clinical trial.

AIMS: Breast cancer is the most common cancer among women, and anthracyclines are the most commonly administered drugs for these patients. Cardiotoxicity is one of the complications, which limits the success of this therapy. Very few studies have evaluated anthracycline toxicities within the first few hours after the first infusion, and the majority of published studies were performed in animal models. The present study aimed to evaluate changes in echocardiographic parameters in women with breast cancer 24 hours after receiving the first dose of an anthracycline. MATERIALS AND METHODS AND RESULTS: The present study included 75 chemotherapy-naive female patients without heart failure, who were diagnosed with breast cancer and were scheduled to undergo anthracycline-based chemotherapy (epirubicin and doxorubicin). During their visits to the Heart Center, the patients underwent detail echocardiographic examination, including assessment of systolic and diastolic function and longitudinal strain. There were no differences in baseline echocardiographic parameters between patients with and those without cardiotoxicity. Cardiotoxicity was observed during follow-up in 14 patients (18.7%). Improvements in left ventricular ejection fraction and global longitudinal strain were observed at 24 hours after administration of the cytotoxic agent in the subgroup of patients without further cardiotoxicity. The changes were transient and the assessment of left ventricular ejection fraction after completion of chemotherapy revealed similar values to those before the treatment. CONCLUSIONS: The findings of our study suggest that transient improvement in contractility and systolic and diastolic function might occur 24 hours after anthracycline administration, especially in patients who do not develop cardiotoxicity.

Variability of platelet response to clopidogrel is not related to adverse cardiovascular events in patients with stable coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: Antiplatelet response to clopidogrel and its influence upon the risk of cardiovascular adverse events among patients with stable coronary artery disease undergoing percutaneous coronary intervention (PCI) has not been investigated fully. METHODS: Two hundred eleven patients treated with aspirin and clopidogrel were included in the study. Immediately before PCI, residual platelet reactivity testing with impedance aggregometry assay and a single-nucleotide polymorphism genotyping analysis targeting variants of CYP2C19, ABCB1, and PON1 genes was performed. After the index PCI, the patients were screened for cardiovascular events 6 months following bare-metal stent implantation or 12 months following drug-eluting stent implantation. RESULTS: High on-treatment platelet reactivity (HTPR) was observed in 19.43% individuals and low-TPR (LTPR) in 26.54%. In multivariate analysis, HTPR was significantly (p < 0.05) associated with a history of diabetes, higher systolic blood pressure, and platelet count comparing to that of other patients. LTPR was significantly associated with no history of hypertension, younger age, lower platelet count, absence of the CYP2C19*2 variant, and lower CRP plasma level. Overall, cardiac adverse events were noted in 14.23% patients. Survival analysis with the Cox proportional hazard model showed no influence of residual platelet reactivity during clopidogrel therapy upon both ischemic and hemorrhagic events. However, significant predictors for composite of major adverse cardiac events and hospitalization for cardiovascular causes were identified (the higher CCS class prior to coronary intervention and the higher creatinine serum concentration). CONCLUSIONS: The platelet response to clopidogrel has no impact upon post-procedural adverse events at mid-term follow-up in patients with stable CAD undergoing PCI. This finding suggests that routine platelet reactivity testing is not beneficial in this group of patients.

Elevated NT-proBNP is associated with unfavorably altered plasma fibrin clot properties in atrial fibrillation.

BACKGROUND: Dense fibrin clot formation and hypofibrinolysis have been reported in atrial fibrillation (AF). It is unclear which factors affect fibrin clot properties in AF. METHODS AND RESULTS: We investigated plasma fibrin clot permeability (Ks), clot lysis time (CLT), endogenous thrombin potential (ETP) as well as other coagulation and fibrinolysis parameters along with N-terminal pro-B-type natriuretic peptide (NT-proBNP) in 160 AF patients (median age, 70.5years). Previous stroke (n=15; 9.4%) was associated with decreased Ks (P=0.04) and longer CLT (P=0.005), together with higher antiplasmin (P=0.03) and lower tissue-type plasminogen activator (P=0.01). Lower Ks (P=0.04) and tendency towards longer CLT (P=0.10) were observed in patients with a left atrium diameter>40mm. Patients with a CHA2DS2-VASc score of 3 or more (82.5%) were characterized by higher thrombin-activatable fibrinolysis inhibitor antigen (P=0.009). Ks was inversely correlated with log NT-proBNP (r=-0.34, P<0.0001), plasminogen activator inhibitor-1 (PAI-1) antigen (r=-0.24, P=0.002) and C-reactive protein (r=-0.18, P=0.02), while CLT was positively correlated with log NT-proBNP (R=0.61, P<0.0001) and ETP (r=0.37, P<0.0001), which were interrelated (r=0.59, P<0.0001). After adjustment for potential confounders, PAI-1 (odds ratio [OR]: 1.14; 95% confidence interval [CI]: 1.02-1.26) was the only independent predictor of low Ks (the lowest quartile,≤6×10-9cm2), while NT-proBNP (OR: 1.21; 95% CI: 1.12-1.31) and PAI-1 (OR: 1.30; 95% CI: 1.12-1.51) both predicted prolonged CLT (the top quartile,≥109min). CONCLUSION: In AF patients prothrombotic fibrin clot properties assessed ex vivo are determined by PAI-1 and NT-proBNP and this phenotype is associated with prior ischemic stroke.

Cardiac safety of systemic therapy in breast cancer patients with high risk of atherosclerosis complications.

AIM: This study was designed to verify the efficacy of breast cancer treatment and its cardiac toxicity in population with significant cardiac comorbidities. MATERIALS & METHODS: Prospective observational study was conducted in 48 patients. RESULTS: The increase and dependence of echocardiographic parameter early/late were observed on hemoglobin level in all patients, and white blood cells and cholesterol in patients with diabetic were reported. Patients undergo left ventricle diameter change on treatment. CONCLUSION: Use of potentially cardiotoxic chemo regimens in breast cancer patients with cardiac comorbidities, with optimized cardiac therapy accordingly can save patients from development of early myocardial dysfunction induced by chemotherapy - limiting factor to minimize the risk is optimization of lipid level, red blood cell count and platelets count.

Alcohol septal ablation in hypertrophic cardiomyopathy utilizing a longitudinal 17-year study (mean 10.8). Observation follow-ups taken at a single medical centre.

BACKGROUND: Alcohol septal ablation (ASA) is a method of treatment in obstructive hypertrophic car-diomyopathy (HOCM), but there is little data on the long-term results of ASA and the natural course after treatment. The aim of the study was to evaluate the results of ASA in HOCM in multiannual observation, and its impact on patient survival, exercise capacity, electrical complications, and changes in the anatomy and function of the heart. METHODS: The study evaluated 47 patients with HOCM with a high left ventricular outflow tract (LVOT gradient) treated between 1997 and 2014 with ASA. Annual examinations evaluated the clinical condi-tion, at rest and with exercise electrocardiogram, Holter monitoring, echocardiography, the evolution of HOCM towards the dilated form, and the frequency of pacemaker implantation. RESULTS: The analysis included data from 34 patients under observation for 3 to 17 (mean 10.8) years. Their age at procedure was 21-65, a mean of 47 years. All patients had permanently reduced LVOT gradient with a mean of 77.36 ± 35.46 to 11.40 ± 10.85 and showed improvement in the performance I to II New York Heart Association. Two out of five deaths had possible cardiac etiology. Fifteen patients received a pacemaker or cardioverter implants. In 4 subjects the long-term observation revealed new wall contractility abnormalities, interpreted as a shift of HOCM to the dilated form. CONCLUSIONS: Alcohol septal ablation permanently eliminated the gradient in LVOT and improved the performance of patients, however it did not prevent a shift of HOCM to the dilated form. Pacemaker implantations are relatively frequent. (Cardiol J 2017; 24, 2: 125-130).

Factors Affecting Exercise Test Performance in Patients After Liver Transplantation.

BACKGROUND: Cardiovascular diseases are a leading cause of morbidity and mortality in solid organ transplant recipients. In addition, low physical activity is a risk factor for cardiac and cerebrovascular complications. OBJECTIVES: This study examined potential relationships between physical activity, health-related quality of life (HRQoL), risk factors for cardiovascular disease, and an exercise test in liver-graft recipients. PATIENTS AND METHODS: A total of 107 participants (62 men/45 women) who had received a liver transplantation (LT) at least 6 months previously were evaluated. Physical activity was assessed using three different questionnaires, while HRQoL was assessed using the medical outcomes study short form (SF)-36 questionnaire, and health behaviors were evaluated using the health behavior inventory (HBI). The exercise test was performed in a standard manner. RESULTS: Seven participants (6.5%) had a positive exercise test, and these individuals were older than those who had a negative exercise test (P = 0.04). A significant association between a negative exercise test and a higher level of physical activity was shown by the Seven-day physical activity recall questionnaire. In addition, HRQoL was improved in various domains of the SF-36 in participants who had a negative exercise test. No correlations between physical activity, the exercise test and healthy behaviors, as assessed via the HBI were observed. CONCLUSIONS: Exercise test performance was affected by lower quality of life and lower physical activity after LT. With the exception of hypertension, well known factors that affect the risk of coronary artery disease had no effect on the exercise test results.

Inflammation markers are associated with metabolic syndrome and ventricular arrhythmia in patients with coronary artery disease.

BACKGROUND: Inflammation plays a major role in the development and progression of atherosclerosis and coronary artery disease (CAD). Inflammation markers, including white blood cell (WBC) count, C-reactive protein (CRP) and interleukin-6 (IL-6), are widely used for cardiovascular risk prediction. The aim of the study was to establish factors associated with WBC, CRP and IL-6 in patients with CAD. Two functional polymorphisms in genes encoding enzymes participating in adenosine metabolism were analyzed (C34T AMPD1, G22A ADA). METHODS: Plasma concentrations of IL-6 were measured using high-sensitivity ELISA kits, and the nephelometric method was used for high-sensitivity CRP (hs-CRP) measurement in 167 CAD patients. RESULTS: Presence of metabolic syndrome (MS) and its components, presence of heart failure, severity of CAD symptoms, severe past ventricular arrhythmia (sustained ventricular tachycardia [sVT] or ventricular fibrillation [VF]), lower left ventricle ejection fraction, higher left ventricle mass index, higher end-diastolic volume and higher number of smoking pack-years were significantly associated with higher WBC, CRP and IL-6. Strong associations with arrhythmia were observed for IL-6 (median 3.90 vs 1.89 pg/mL, p<0.00001) and CRP concentration (6.32 vs 1.47 mg/L, p=0.00009), while MS was associated most strongly with IL-6. CRP and IL-6 were independent markers discriminating patients with sVT or VF. There were no associations between AMPD1 or ADA genotypes and inflammation markers. CONCLUSIONS: WBC, CRP and IL-6 are strongly associated with components of the metabolic syndrome. Their strong association with life-threatening ventricular arrhythmia emphasizes the proarrhythmic role of inflammation in the increased cardiovascular risk of CAD patients.

[The role of biochemical markers with special regard to troponin, CK-MB, NT-proBNP as early biomarkers of cardiotoxicity among women after chemotherapy due to breast cancer].

Introduction: Cardiotoxicity of drugs in oncology is a growing problem which cardiologists and oncologists have to struggle with. So far, researchers have been looking for biochemical markers which could help to extract a group more prone to developing complications after chemotherapy. Authors' reports are inconsistent in this topic. Aim: This study assesses the role of troponin I, CK-MB and NT-proBNP as early predictive markers for later cardiotoxicity among patients with breast cancer treated with chemotherapy. Methods: One hundred five patients with breast cancer, without either heart failure or more than moderate severity of valvular heart diseases were qualified to the study. Results: NT-proBNP concentration significantly increased just after the first cycle of chemotherapy, either in a subgroup which developed cardiotoxicity or without this end point (p<0.001, p=0.004). CK-MB did not change significantly during observation. Troponin I did not change in any of the patients. During observation HDL-cholesterol concentration significantly decreased. A transient increase of the concentration of LDL-cholesterol had been noted, but later it decreased below baseline level. Conclusion: Troponin I has too low sensitivity to be used as a prognostic marker for further cardiotoxicity after chemotherapy. No prognostic values have been noted of NT-proBNP and CK-MB due to the lack of differences in both a subgroup with and without cardiotoxicity.

[Coronary artery disease in women ­ how to prevent heart failure after myocardial infarction?].

Cardiovascular disease has been the most common cause of death and disability in women. The prevelence of cardiovascular diseases in women increases dramatically with age as the population ages and women's life expectancy inareases. Compared with men, women with coronary artery diseases are older and more likely to have hyprtension, diabetes and congestive heart failure. Principles of diagnostic and therapeutic management of women are similar to those in men. Clinical trials focusing on treatment alternatives in women have demonstrated improvements in outcomes with advances in technologies and contemporary therapies. All efforts should be focused on the proper screening, prevention and referral for treatment of women with coronary artery disease in order to impact the increasing mortality from heart failure.

[Pregnant woman with pulmonary hypertension]. / Nadcisnienie plucne w ciazy.

Pulmonary hypertension is a disease with diverse etiology. According to the New ESC guidelines, pregnancy is contraindicated for a patent with pulmonary hypertension and qualify such patent to class IV NYHA, regardless of the reason of hypertension. Pregnancy is revived for a patient with pulmonary hypertension despite of the fact that recent treatment methods including specific therapy with the endothelin receptor antagonistst (bosentan), phosphodiesterase inhibitors (sildenafil) and prostacyclin analogs (iloprost) were introduced. In the case of coincidence of pregnancy and pulmonary hypertension, patients should be managed in a center with expertise in pulmonary hypertension with all therapeutic options available.

Prognostic role of troponin and natriuretic peptides as biomarkers for deterioration of left ventricular ejection fraction after chemotherapy.

Cardiotoxicity due to anthracyclines, trastuzumab and other potential cardiotoxic drugs is still a problem of modern chemotherapy. For years researchers have tried to find biological markers that can predict changes in the heart. The most thoroughly tested markers are troponin and natriuretic peptides. Some studies have proven that these markers can indeed be useful. In studies which have shown the predictive role of troponin I the assessment of this marker was performed very frequently. It is not possible to carry out such serial measurements in many centers because of typical 1-day hospital stay times. The predictive role of natriuretic peptides still needs further investigation. This review considers the newest research from recent years.

[Sick sinus syndrome and conduction disorders in women--frequency, treatment]. / Choroba wezla zatokowego, zaburzenia przewodzenia przedsionkowo-komorowego u kobiet-czestosc wystepowania, postepowanie.

Conduction disorders in women are often presented as sick sinus syndrome in comparison to men who have more often disturbances of AV conduction diseases and sinus carotid diseases. Nearly every heart disease with prevalence of ischeamic heart disease and idiopathic degenerative fibrotic process, which leads to reduction number of trigger cells, can result in conduction disorders. As a gold standard in treatment is pacemaker implantation with appropriate pacing mode, after exclusion a reversable reason of the disease.