Kamil Bujak

The Prognostic Role of Red Blood Cell Distribution Width in Coronary Artery Disease: A Review of the Pathophysiology.

Red blood cell distribution width (RDW) is a measure of red blood cell volume variations (anisocytosis) and is reported as part of a standard complete blood count. In recent years, numerous studies have noted the importance of RDW as a predictor of poor clinical outcomes in the settings of various diseases, including coronary artery disease (CAD). In this paper, we discuss the prognostic value of RDW in CAD and describe the pathophysiological connection between RDW and acute coronary syndrome. In our opinion, the negative prognostic effects of elevated RDW levels may be attributed to the adverse effects of independent risk factors such as inflammation, oxidative stress, and vitamin D3 and iron deficiency on bone marrow function (erythropoiesis). Elevated RDW values may reflect the intensity of these phenomena and their unfavorable impacts on bone marrow erythropoiesis. Furthermore, decreased red blood cell deformability among patients with higher RDW values impairs blood flow through the microcirculation, resulting in the diminution of oxygen supply at the tissue level, particularly among patients suffering from myocardial infarction treated with urgent revascularization.

The platelet-to-lymphocyte ratio as a predictor of all-cause mortality in patients with coronary artery disease undergoing elective percutaneous coronary intervention and stent implantation

Background There is no data regarding the association between the platelet-to-lymphocyte ratio (PLR) and long-term mortality in patients with stable coronary artery disease (SCAD). The aim of this study is to evaluate the utility of the pre-procedural PLR for predicting long-term, all-cause mortality in patients with SCAD undergoing percutaneous coronary intervention (PCI) and stent implantation. Methods We analyzed a total of 2959 consecutive patients with SCAD who underwent PCI (balloon angioplasty followed by stent implantation or direct stenting) between July 2006 and December 2011 at our institution. The patients were stratified into tertiles according to their admission PLR. The association between the PLR value and the outcomes was assessed using Cox proportional regression analysis after adjusting for clinical angiographic and laboratory data. Results During median follow-up of 1124 days, mortality was highest in patients with PLR within the 3rd tertile as compared to the 2nd and the 1st tertile (11.0% vs 8.7% vs. 9.6%, respectively, p = 0.03). PLR remained associated with mortality in multivariable analysis including clinical variables, ejection fraction and angiographic parameters HR (per 10 units increase) = 1.02 [95%CI,1.01 ÷ 1.04, p = 0.006]. After adjustment for the eGFR and hemoglobin levels, PLR was however no longer significantly associated with mortality. Conclusion PLR has potential predictive value in patients with SCAD, which has not been reported previously, but statistical significance disappears after adjusting for estimated glomerular filtration rate (eGFR) and hemoglobin levels as a potential confounding variable.

Prognostic implications of mean platelet volume on short- and long-term outcomes among patients with non-ST-segment elevation myocardial infarction treated with percutaneous coronary intervention: A single-center large observational study

Abstract Background: Mean platelet volume (MPV) is a simple and reliable indicator of platelet size that correlates with platelet activation and their ability to aggregate. We studied the predictive value of MPV in patients with non-ST-segment elevation myocardial infarction (NSTEMI) treated with percutaneous coronary intervention (PCI). Methods: We analyzed the consecutive records of 1001 patients who were hospitalized due to NSTEMI at our center. The primary end point was a composite end point that included the rates of all-cause death, non-fatal myocardial infarction, and acute coronary syndrome (ACS) driven revascularization at 12 months. The enrolled patients were stratified according to the quartile of the MPV level at admission. Results: Along with the increasing quartile of MPV, the 12-month composite end point increased significantly (p = 0.010), and this association remained significant after the risk-adjusted analyses (per 1 fL higher MPV; adjusted hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.02–1.27; p = 0.026). In the multivariate analysis, the MPV was also an independent factor of all-cause mortality (per 1 fL increase; adjusted HR 1.34; 95% CI 1.12–1.61; p = 0.0014) and death or non-fatal myocardial infarction (per 1 fL increase; adjusted HR 1.16; 95% CI 1.03–1.31; p = 0.017). Conclusion: In patients with NSTEMI treated with PCI, a high MPV value was associated with a significantly increased incidence of long-term adverse events, particularly for all-cause mortality.

Functional polymorphism rs710218 in the gene coding GLUT1 protein is associated with in-stent restenosis

AIM To analyze the association between in-stent restenosis (ISR) and polymorphisms in genes coding IGF-1, IGFBP3, ITGB3 and GLUT1, which play an important role in the smooth muscle cell proliferation and extracellular matrix synthesis - the main components of neointima. MATERIALS & METHODS We analyzed 265 patients who underwent bare metal stent implantation. RESULTS The differences in the occurrence of ISR between genotypes of the analyzed polymorphisms in the IGF-1, IGFBP3 and ITGB3 were not statistically significant. The T/T genotype of the rs710218 polymorphism in the GLUT1 (SLC2A1) gene was more common in the ISR group compared with non-ISR patients (81.1 vs 64.8%; p = 0.02). In a multivariable model the A/A and A/T genotype remained correlated with lower occurrence of ISR (odds ratio: 0.45; 95% CI: 0.21-0.97; p = 0.03). CONCLUSION The rs710218 polymorphism in the gene coding GLUT1 protein is a novel risk factor for ISR.

The Relationships between Polymorphisms in Genes Encoding the Growth Factors TGF-β1, PDGFB, EGF, bFGF and VEGF-A and the Restenosis Process in Patients with Stable Coronary Artery Disease Treated with Bare Metal Stent.

Background Neointima forming after stent implantation consists of vascular smooth muscle cells (VSMCs) in 90%. Growth factors TGF-β1, PDGFB, EGF, bFGF and VEGF-A play an important role in VSMC proliferation and migration to the tunica intima after arterial wall injury. The aim of this paper was an analysis of functional polymorphisms in genes encoding TGF-β1, PDGFB, EGF, bFGF and VEGF-A in relation to in-stent restenosis (ISR). Materials and Methods 265 patients with a stable coronary artery disease (SCAD) hospitalized in our center in the years 2007–2011 were included in the study. All patients underwent stent implantation at admission to the hospital and had another coronary angiography performed due to recurrence of the ailments or a positive result of the test assessing the coronary flow reserve. Angiographically significant ISR was defined as stenosis >50% in the stented coronary artery segment. The patients were divided into two groups–with angiographically significant ISR (n = 53) and without significant ISR (n = 212). Additionally, the assessment of late lumen loss (LLL) in vessel was performed. EGF rs4444903 polymorphism was genotyped using the PCR-RFLP method whilst rs1800470 (TGFB1), rs2285094 (PDGFB) rs308395 (bFGF) and rs699947 (VEGF-A) were determined using the TaqMan method. Results Angiographically significant ISR was significantly less frequently observed in the group of patients with the A/A genotype of rs1800470 polymorphism (TGFB1) versus patients with A/G and G/G genotypes. In the multivariable analysis, LLL was significantly lower in patients with the A/A genotype of rs1800470 (TGFB1) versus those with the A/G and G/G genotypes and higher in patients with the A/A genotype of the VEGF-A polymorphism versus the A/C and C/C genotypes. The C/C genotype of rs2285094 (PDGFB) was associated with greater LLL compared to C/T heterozygotes and T/T homozygotes. Conclusions The polymorphisms rs1800470, rs2285094 and rs6999447 of the TGFB1, PDGFB and VEGF-A genes, respectively, are associated with LLL in patients with SCAD treated by PCI with a metal stent implantation.

Conduction disturbances after transcatheter aortic valve implantation procedures – predictors and management

Transcatheter aortic valve implantation (TAVI) has become a safe and efficient alternative to cardiac surgery in patients with severe aortic stenosis. In many countries the number of performed TAVI procedures equals the number of surgical implantations. Indications for TAVI are becoming more liberal, allowing a wider spectrum of patients to benefit from the advantages of transcatheter therapy. Due to its invasive nature, TAVI is associated with some complications such as conduction disturbances. Although these disturbances are usually not lethal, they have a great influence on patients’ state and long term-survival. The most relevant and common are His’ bundle branch blocks, atrioventricular blocks, and need for permanent pacemaker implantation. With the frequency at 10% to even 50%, conduction abnormalities are among the most important TAVI-related adverse events. Risk factors for conduction disturbances include age, anatomy of the heart, periprocedural factors, type of implanted valve, and comorbidities. Severity of occurring complications varies; therefore selection of a proper treatment approach is required. Considered as the most effective management, permanent pacemaker implantation turned out to negatively influence both recovery and survival. Moreover, there is no expert consensus on use of resynchronization therapy after TAVI. In this paper, the authors present a comprehensive analysis of the most common conduction disturbances accompanying TAVI, factors related to their occurrence, and treatment approach.

Who is eligible for randomized trials? A comparison between the exclusion criteria defined by the ISCHEMIA trial and 3102 real-world patients with stable coronary artery disease undergoing stent implantation in a single cardiology center

BackgroundRandomized controlled trials are the gold standard for evaluating therapy; however, controversy exists regarding the applicability of such results to daily practice, as patients are often pre-selected and may not reflect real-world clinical settings. We studied the eligibility criteria for 3102 “real-life” patients with stable coronary artery disease (SCAD) according to the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial exclusion criteria. The aim of our analysis was to estimate the percentage of real-life patients who would have met the exclusion criteria for the ISCHEMIA trial.MethodsWe analyzed 3102 patients with SCAD referred to the Silesian Center for Heart Disease who underwent both coronary angiography and stent implantation between January 2006 and December 2011. The patients were divided into two groups. Group A was composed of patients with SCAD who would have been excluded from the ongoing ISCHEMIA trial, whereas group B represented the remaining patients.ResultsA total of 1900 (61.3 %) patients met at least one of the exclusion criteria. The most frequent exclusion criterion noted was revascularization within the previous 12 months (938 patients; 49.4 %), followed by unacceptable level of angina symptoms (532 patients; 28 %), low ejection fraction (467 patients; 24.6 %), and acute coronary syndrome within the previous 2 months (456 patients; 24 %). Patients from our cohort who would have been excluded from the ISCHEMIA trial were older, had more comorbidities, and experienced worse long-term outcomes.ConclusionsThe ISCHEMIA trial exclusion criteria ruled out the majority of the patients with SCAD undergoing percutaneous coronary intervention in “real life”. Our cohort of patients who would have been excluded from the ISCHEMIA trial had more comorbidities and experienced significantly worse long-term outcomes than patients who did not meet the ISCHEMIA trial exclusion criteria.Trial registrationClinicalTrials.gov NCT01471522.

The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease.

BackgroundDespite the important roles of vascular smooth muscle cells and endothelial cells in atherosclerotic lesion formation, data regarding the associations of functional polymorphisms in the genes encoding growth factors with the severity of coronary artery disease (CAD) are lacking. The aim of the present study is to analyze the relationships between functional polymorphisms in genes encoding basic fibroblast growth factor (bFGF, FGF2), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), platelet derived growth factor-B (PDGFB), transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor A (VEGF-A) and the severity of coronary atherosclerosis in patients with stable CAD undergoing their first coronary angiography.MethodsIn total, 319 patients with stable CAD who underwent their first coronary angiography at the Silesian Centre for Heart Diseases in Zabrze, Poland were included in the analysis. CAD burden was assessed using the Gensini score. The TaqMan method was used for genotyping of selected functional polymorphisms in the FGF2, PDGFB, TGFB1, IGF1 and VEGFA genes, while rs4444903 in the EGF gene was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The associations between the selected polymorphisms and the Gensini were calculated both for the whole cohort and for a subgroup of patients without previous myocardial infarction (MI).ResultsThere were no differences in the distribution of the Gensini score between the genotypes of the analyzed polymorphisms in FGF2, EGF, IGF1, PDFGB, and TGFB1 in the whole cohort and in the subgroup of patients without previous MI. The Gensini score for VEGFA rs699947 single-nucleotide polymorphism (SNP) in patients without previous myocardial infarction, after correction for multiple testing, was highest in patients with the A/A genotype, lower in heterozygotes and lowest in patients with the C/C genotype, (p value for trend = 0.013, false discovery rate (FDR) = 0.02). After adjustment for clinical variables, and correction for multiple comparisons the association between the VEGFA genotype and Gensini score remained only nominally significant (p = 0.04, FDR = 0.19) under the dominant genetic model in patients without previous MI.ConclusionsWe were unable to find strong association between analyzed polymorphisms in growth factors and the severity of coronary artery disease, although there was a trend toward association between rs699947 and the severity of CAD in patients without previous MI.

Relationship of the rs1799752 polymorphism of the angiotensin-converting enzyme gene and the rs699 polymorphism of the angiotensinogen gene to the process of in-stent restenosis in a population of Polish patients with stable coronary artery disease

PURPOSE The renin-angiotensin-aldosterone system may influence in-stent restenosis (ISR) via angiotensin II, which stimulates the production of growth factors for smooth muscle cells. The aim of this work is to assess the influence of the rs1799752 polymorphism of the angiotensin-converting enzyme (ACE) gene and the rs699 polymorphism of the angiotensinogen (AGT) gene on the ISR in Polish patients with stable coronary artery disease (SCAD) who underwent stent implantation. MATERIAL/METHODS Two hundred and sixty-five patients with SCAD were included in the study. All patients underwent stent implantation upon admission to the hospital and had subsequent coronary angiography performed. The patients were divided into two groups - those with significant ISR (n=53) and those without ISR (n=212). The ACE polymorphism was assessed using the classical PCR method and the AGT polymorphism was determined using the TaqMan method for SNP genotyping. RESULTS No difference in the frequency of angiographically significant ISR occurrence associated with the different ACE and AGT gene polymorphisms was observed. In a multivariable analysis, after correction for clinical variables, the relationship between the ACE and AGT genotypes within the scope of the analyzed polymorphisms and the process of restenosis was not found using a dominant, recessive and log-additive model. Late lumen loss was also independent of the genotypes of the polymorphisms before and after correction with angiographic variables. CONCLUSIONS The rs1799752 polymorphism and the rs699 polymorphism had no relationship with the occurrence of angiographically significant ISR and late lumen loss in a group of Polish patients who underwent metal stent implantation.

Risk factors for paravalvular leak after transcatheter aortic valve implantation.

Many studies have shown that transcatheter aortic valve implantation (TAVI) improves outcomes in patients with severe aortic stenosis in whom a classical surgical procedure cannot be performed due to the high risk. As one of the most frequent periprocedural complications of TAVI, paravalvular leak significantly affects the short- and long-term prognosis for patients undergoing implantation. In this paper, we analyze the most significant anatomical and procedural predictors of paravalvular leak after TAVI.