Mobilization of bone marrow-derived progenitor cells in acute coronary syndromes.

Two hypotheses explain the role of adult progenitor cells in myocardial regeneration. Stem cell plasticity which involves mobilization of stem cells from the bone marrow and other niches, homing to the area of tissue injury and transdifferentiation into functional cardiomyocytes. Alternative hypothesis is based on the observations that bone marrow harbors a heterogenous population of cells positive for CXCR4 - receptor for chemokine SDF-1. This population of non-hematopoietic cells expresses genes specific for early muscle, myocardial and endothelial progenitor cells (EPC). These tissue-committed stem cells circulate in the peripheral blood at low numbers and can be mobilized by hematopoietic cytokines in the setting of myocardial ischemia. Endothelial precursors capable of transforming into mature, functional endothelial cells are present in the pool of peripheral mononuclear cells in circulation. Their number significantly increases in acute myocardial infarction (AMI) with subsequent decrease after 1 month, as well as in patients with unstable angina in comparison to stable coronary heart disease (CHD). There are numerous physiological and pathological stimuli which influence the number of circulating EPC such as regular physical activity, medications (statins, PPAR-gamma agonists, estrogens), as well as numerous inflammatory and hematopoietic cytokines. Mobilization of stem cells in AMI involves not only the endothelial progenitors but also hematopoietic, non-hematopoietic stem cells and most probably the mesenchymal cells. In healthy subjects and patients with stable CHD, small number of circulating CD34+, CXCR4+, CD117+, c-met+ and CD34/CD117+ stem cells can be detected. In patients with AMI, a significant increase in CD34+/CXCR4+, CD117+, c-met+ and CD34/CD117+ stem cell number the in peripheral blood was demonstrated with parallel increase in mRNA expression for early cardiac, muscle and endothelial markers in peripheral blood mononuclear cells. The maximum number of stem cells was found early in ST-segment elevation myocardial infarction

Clinical trials using autologous bone marrow and peripheral blood-derived progenitor cells in patients with acute myocardial infarction.

This paper discusses the current data concerning the results of major clinical trials using bone marrow-derived and peripheral blood-derived stem/progenitor cells in treatment of patients with acute myocardial infarction (AMI) and depressed left ventricular ejection fraction. In all major trials (TOPCARE-AMI, BOOST), the primary outcome measure was increase in left ventricular systolic function (LVEF) and left ventricle remodeling. The most consistent finding is the significant increase in LVEF. Some trials suggest also reduction of left ventricular remodeling. Although the absolute LVEF increase is small (6-9%), it may substantially contribute to the improvement of global LV contractility. None of the studies in AMI patients treated with intracoronary infusion of progenitor cells revealed excess risk of arrythmia, restenosis or other adverse effects attributable to the therapy. The exact mechanism of improved myocardial contractile function remains unknown, however, there are several possible explanations: therapeutic angiogenesis improving the blood supply to the infarct border zone, paracrine modulation of myocardial fibrosis and remodeling (e.g. inhibition of myocyte apoptosis) and transdifferentiation of stem/progenitor cells into functional cardiomyocytes. No study showed the superiority of the particular subpopulation of autologous progenitor cells in terms of left ventricular function improvement in AMI. In fact, most of the clinical trials used the whole population of mononuclear bone marrow-derived progenitor cells, peripheral blood derived progenitor cells (endothelial progenitors)

ARISTOTLE RE-LYs on the ROCKET. What’s new in stroke prevention in patients with atrial fibrillation?

Warfarin has long been considered the gold standard for stroke prevention in patients with atrial fibrillation (AF). Recently, three major trials comparing the efficacy and safety of new drugs: a thrombin inhibitor dabigatran and two inhibitors of factor Xa — rivaroxaban and apixaban, with that of warfarin, have been published. The aim of this paper is to present the main results of the RE-LY, ROCKET AF and ARISTOTLE trials, compare study populations and outcomes, and discuss clinical implications of their results for the long-term anticoagulation in patients with nonvalvular AF. (Cardiol J 2012; 19, 1: 4–10

Traditional, forgotten and new left ventricular systolic function parameters on a 64-row multidetector cardiac computed tomography: A reproducibility study

Background: Multidetector computed tomography angiography (MDCT) can provide data regardingcardiac function if a retrospective scanning is applied. We aimed at examination of thereproducibility of traditional and more sensitive parameters of the left ventricular (LV) contractilityby means of a 64-row CT in order to establish errors of measurement and to determine limits thatallow for a reliable detection of their changes.Methods and Results: A random sample of 25 individuals, including 15 females (aged 64 ± 13years) and 10 males (54 ± 13 years), who had MDCT examination were retrospectively includedin this study. Data reconstructions were performed on a dedicated workstation. In each case, axialimage series were created with a 10% step from 0% to 90% of the RR interval using a 2 mm slicethickness. LV volume was determined in each phase. Detailed LV volume changes within phaseswere analyzed to determine the largest difference between the neighbor phases (peak ejection volume,PEV, mL) during systole and to calculate the peak ejection rate (PER i.e. PEV/phase duration[1/10th of RR interval], mL/s). The derived parameters were calculated as the PER normalized forLVEDV (PER-V, 1/s), the PER normalized for LVM (PER-M, mL/g × s) and the PER normalizedfor LVEDV times the PER normalized for LVM product (PER-VM, ml/g × s2). Considering the errorspercentages, the respective values for intra- and inter-observer errors were around 5% and 8%for standard LV systolic measures. The percentage intra-observer errors’ ranged between –7.8% and–10.8%, and the inter-observer errors’ ranged between –11.8% and –15.7% for both PEV and PER.For the same reader, the percentage errors ranged between –8.7% and +11.9% for PER-V, –10% and+12.7% for PER-M and –18.2% and +24% for PER-VM. For the independent reader the correspondingvalues were –15.2% and +15.5%, –12.3% and +16.3%, and –26.6% and +30.9%. The intra--class coeffi cients for repeated measurements for both the same reader (intra-observer) or independentreader (inter-observer) did reach values above 0.9 and around 0.8, respectively.Conclusions: We concluded that traditional LV systolic parameters, as well as more sensitive measuresof cardiac contractility could be determined reliably by means of a 64-row MDCT. The errorsfor global LV systolic function measures amount to about 5%, for PEV and PER about 15% and forthe PER-derived parameters about 25%. The measurement errors established might help to assessthe signifi cance of changes in repeated MDCT examinations

Traditional risk factors and coronary artery calcium in young adults

Background and methods: 362 symptomatic subjects of 45 years of age or younger were selected from a large database of around 4100 persons who underwent coronary artery calcium (CAC) scoring by means of a 64-multidetector computed tomography (MDCT). Amongst them, a group with the CAC > 0 Agatston units (n = 65) and a group with no detectable calcium (CAC = 0, n = 297) were compared in terms of risk factors presence. Risk factors considered were gender, body mass index, smoking habits, blood pressure level, blood lipids, presence of diabetes mellitus, family history of cardiovascular disease, and physical activity. Results: The vast majority of subjects with a positive CAC were males (54, 83.1%) compared to those with a negative CAC (147, 49.5%, p 0 were observed in obese subjects (38.5% vs. 24.2%, p 0 (76.9% vs. 60.6%, p < 0.05). Also, the frequency of a positive CAC was significantly higher in patients with diabetes mellitus (10.8%), compared to those without diabetes mellitus (4.0%, p < 0.05). Effects of high lipids, family history, and physical activity were not observed. Accumulation of at least 4 risk factors was associated with more frequent positive CAC (26.0 vs. 15.9%, p < 0.05). Multivariate regression analysis showed that only male gender and presence of diabetes mellitus were independent predictors of a positive CAC in younger subjects (F = 5.06, p < 0.001, multiple R = 0.321). Conclusions: Traditional risk factors, apart from gender and diabetes mellitus, do not seem to allow for distinguishing young persons with a premature coronary atherosclerosis. Therefore, CAC scoring might be considered justified in symptomatic young men with diabetes mellitus

Relationship between R-R interval variation and left ventricular function in sinus rhythm and atrial fibrillation as estimated by means of heart rate variability fraction

Background: Reduced heart rate variability (HRV) is associated with a poor outcome in patients with sinus rhythm (SR) or atrial fibrillation (AF). However, cut-off points for HRV measures differ between SR and AF. We hypothesized that a global index of 24-hour HRV based on evaluation of scatterplot would describe HRV irrespective of cardiac rhythm. Methods: 407 patients with ischemic heart disease (317 male, 90 female, mean age 57 &#177; 9 years) were studied. 331 patients had SR and 76 patients had AF. 24-hour ECGs were recorded, and standard HRV indices were calculated. Scatterplots was used to determine the HRV fraction (HRVF, %). HRV measures were compared in respect to left ventricular ejection fraction (LVEF &#163; 35% or > 35%). Results: Standard HRV measures were higher in AF-patients despite the mean RR interval was lower. In patients with LVEF &#163; 35%, standard HRV indices were lower in SR group, in AF group only SDNN and RMSSD were reduced. The HRVF was comparably reduced (SR 39.3 &#177; 15.3%, AF 37.3 &#177; 17.9%). In patients with LVEF > 35%, HRVF did not differ between SR (47.2 &#177; &#177; 10.5%) and AF (46.1 &#177; 12.1%). The HRVF correlated with SDNN and SDANN (~0.85) in SR. Correlations were weaker in AF (~0.6). Standard HRV indices and HRVF showed similar relations with LVEF, but only in AF at the same range. Conclusions: The HRV fraction allows for HRV evaluation irrespective of cardiac rhythm. The index elicited a similar dependence of HRV on left ventricular function in SR and AF. (Cardiol J 2011; 18, 5: 538&#8211;545

Diagnostic value of flow mediated dilatation measurement for coronary artery lesions in men under 45 years of age

Background: In those without symptoms of coronary artery disease (CAD), the incidence of coronary events is still high. The aim of this study was to evaluate whether flow mediated dilatation (FMD) is a useful tool in identifying those with CAD in who are under 45 years of age. Methods and results: Seventy five men below 45 years of age, hospitalized in order to perform elective coronary angiography, were enrolled into the study. Based on coronary angiography findings, they were divided into two groups: study group (Group A, n = 55) with obstructive coronary lesions and the control group (Group B, n = 20) without significant lesions in coronary arteries. In all subjects atherosclerosis risk factors were analyzed. Endothelial dysfunction was assessed in ultrasound via FMD. FMD was significantly lower in the study group than in the control group (3.92 &#177; 1.1 vs 6.51 &#177; 1.1, p < 0.001). FMD, as well as age, diabetes and positive family history, appeared to be statistically significant CAD risk factors. AUROC for FMD was 0.957 (p < 0.001), meaning this model had an almost complete ability to predict the presence of CAD. AUROC for CAD diagnosis on the basis of significant clinical parameters was 0.992 (p < 0.001), also representing almost complete ability of this model to identify asymptomatic subjects with CAD risk. Conclusions: The evaluation of endothelial function by the use of FMD in the population of men below 45 years of age with diabetes and positive family history can help in identifying subjects at high risk of coronary artery disease. (Cardiol J 2010; 17, 3: 288-292

Coronary artery visualization using a 64-row multi-slice computed tomography in unselected patients with definite or suspected coronary artery disease: A comparison with invasive coronary angiography

Background: Multi-slice computed tomography (MSCT) is becoming an increasingly acknowledged means of visualizing coronary arteries. The accuracy of 64-MSCT is still a subject of clinical evaluation. Our study, performed with a 64-slice scanner, was intended to assess the concordance of coronary artery lumen visualization in MSCT and invasive coronary angiography (ICA), both in post-revascularization and previously medically treated patients. Methods: We examined data from 73 patients (31 women, 42 men, mean age 59 years) referred to our hospital in 2006 and 2007 who underwent MSCT and subsequent ICA. Twenty two patients had a history of previous revascularization. Of the remaining 51 patients with intermediate coronary artery disease probability, the indication for 64-MSCT was suspicion of coronary artery disease. MSCT coronary angiography was performed with Aquilion 64 scanner (Toshiba, Japan). We evaluated 15 segments of four native coronary arteries (RCA, LM, LAD and Cx in all patients plus 11 arterial and 22 venous conduits). The cut-off value for significant stenosis was the lumen cross section area reduction exceeding 50%, regardless of segment. Results: Regarding native arteries, MSCT and ICA findings were coherent in 80.8% of all patients, 93.8% of vessels, and 98.4% of segments. MSCT coronary stent patency evaluation was 90.9% correct. The by-pass grafts evaluation was entirely concordant in both methods. The respiratory and heart rate variability artifacts hindered the MSCT analysis in ten patients (13.7%). The artifacts occurrence in misinterpreted studies was nearly two-fold higher than in those that were coherent (21.4% vs. 11.9%). Conclusions: We concluded that a reliable evaluation of the coronaries by means of 64-MSCT is feasible both in patients with suspected coronary artery disease and those with definite coronary artery disease who had previous coronary intervention. Patient selection and co-operation is necessary to avoid respiratory and heart rate variability artifacts that may hinder analysis

The prognostic role of electrocardiographic left ventricular mass assessment for identifying PCI-treated patients with acute ST-elevation myocardial infarction at high risk of unfavourable outcome

Background: In prognostic terms, evaluation of an ECG recording in acute myocardial infarction (AMI) appears to be inferior to echocardiographic (ECHO) assessment of left ventricular remodelling and the activities of cardiac enzymes and certain hormones. It was our hypothesis that, in the era of interventional treatment of AMI, some ECG parameters are still valid for the purpose of risk stratification. Methods: A total of 66 consecutive patients with AMI (43 male and 23 female, with a mean age of 61 &#177; 11 years) were treated with primary percutaneous coronary intervention (PCI). In each patient ECG and ECHO examinations were performed within 5-7 days of admission for the detection of left ventricular hypertrophy (LVH). In further analysis the following ECG- based LVH parameters were taken into consideration: Sokolov-Lyon voltage duration (SLVd), Cornell voltage duration CVd), 12-lead QRS voltage duration (12QRSVd), their product with QRS duration and an ECG index of left ventricular mass (LVMIECG). Patients were followed for 6 months. The combined end-point included death, infarction, a need for prompt coronary intervention and hospitalization for heart failure. Results: The combined end-point was observed in 16 patients (24.2%). Survival analysis revealed that the most important prognostic factors were associated with a prolongation of the QRS duration. Increased SLVd was found in 43% of the patients with events compared to 14% in those without them (p < 0.01), CVd in 43% vs. 12% (p < 0.05), 12QRSVd in 81% vs. 44% (p < 0.05) and LVMIECG in 75% vs. 26%, p < 0.001). There was no evidence for a difference in Cornell voltage. Univariate logistic regression indicated a 4-fold to 8-fold increase in the risk of events associated with abnormal SLV, SLVd or LVMIECG. Multivariate Cox analysis showed that the LVH presence in the ECG, defined as an increased SLVd product or increased LVMIECG, was an independent predictor of cardiovascular events after AMI. Conclusions: In the era of interventional treatment of AMI, the ECG features of left ventricular hypertrophy carry independent significant prognostic information. (Cardiol J 2007; 14: 347&#8211;354