Unmasking the Silent Threat: COVID-19's Pervasive Impact on Renal Allografts.

OBJECTIVES: Growing evidence has highlighted the substantial effects of COVID-19 on kidneys, ranging from mild proteinuria to severe acute kidney injury. However, comprehensive assessments of histopathological features in renal allograft biopsies are lacking. MATERIALS AND METHODS: Seventeen kidney transplant recipients with COVID-19 between March 2020 and November 2022 were evaluated. Clinical characteristics, pathological findings, and outcomes were studied. RESULTS: Six kidney transplant recipients (35.3%) developed acute kidney injury, leading to the requirement for hemodialysis. COVID-19 severity, as indicated by pneumonia (P = .028) and hospitalization (P = .002), was significantly associated with development of acute kidney injury. Most patients with COVID-19 (82.4%) showed considerably increased proteinuria levels (82.4%), along with presence of new-onset microscopic hematuria (35.3%) and nephrotic syndrome (58.8%). Tubular viral inclusionlike changes were detected in 47.1% of cases and were associated with a higher risk of graft loss (75%). Thrombotic microangiopathy and endothelial cell swelling in glomeruli were prevalent, highlighting extensive endothelial cell injury. Most recipients (88.2%) experienced rejection after COVID-19, with graft loss occurring in 46.7% of these cases. Biopsies revealed collapsing (n = 5), noncollapsing (n = 3), and recurrent (n = 2) focal segmental glomerulosclerosis, as well as acute tubulointerstitial nephritis (n = 3), crescentic glomerulonephritis with immunoglobulin A nephropathy (n = 1), and membranoproliferative glomerulonephritis (n = 1), in 129.7 ± 33 days. Eight patients experienced graft loss (8.2 ± 2 mo posttransplant). Hospitalization (P = .044) and viralinclusion-like nuclear changes in tubules (P = .044) significantly influenced graft survival. Collapsing (60%) and noncollapsing (66.7%) focal segmental glomerulosclerosis increased the risk of graft loss. CONCLUSIONS: COVID-19 has had a multifaceted and enduring effect on renal allografts, urging the need for meticulous monitoring and tailored management strategies to mitigate the risk of severe kidney-related complications and graft loss in this vulnerable population.

Importance of Follow-Up Biopsies in the Prediction of Renal Allograft Survival Following Polyomavirus-Associated Nephropathy.

OBJECTIVES: Allograft biopsy is the gold standard for diagnosing polyomavirus-associated nephropathy. We aimed to establish the effects of histopathologic findings proposed by the Banff Polyomavirus Working Group on graft outcome. We also aimed to understand the clinical importance of follow-up biopsies for patients with polyomavirus-associated nephropathy. MATERIALS AND METHODS: Our study included 22 patients with polyomavirus-associated nephropathy. All biopsies were classified according to the latest Banff Polyomavirus Working Group classification. Follow-up biopsies of all patients were evaluated in detail. RESULTS: The mean interval between polyomavirus-associated nephropathy and transplant was 10 ± 1.6 months. Of 22 patients, biopsy revealed stage 1 in 3 (13.6%), stage 2 in 17 (77.3%), and stage 3 in 2 patients (9.1%). Fourteen patients (63.6%) had polyomavirus viral load 3, 5 (22.7%) had polyomavirus viral load 2, and 3 had polyomavirus viral load 1. Among patients included in analyses, 18.2% had antibody-mediated rejection and 27.2% had T-cell-mediated rejection simultaneously with polyomavirus-associated nephropathy. Graft loss increased with increasing polyomavirus-associated nephropathy class and polyomavirus viral load (P = .015 and P = .002, respectively). The mean time of graft survival decreased with increasing degree of tubulitis, interstitial inflammation, plasma infiltration, and neutrophil infiltration. Patients with interstitial fibrosis, glomerular polyoma, and cortical plus medullar involvement showed earlier graft loss. Follow-up biopsies showed that diffuse interstitial fibrosis or persistent inflam-mation negatively influenced graft loss. CONCLUSIONS: The Banff Polyomavirus Working Group's schema significantly correlated with graft outcome. Early detection of polyomavirus-associated nephro-pathy and subsequent detection of persistent inflammation and interstitial fibrosis and tubular atrophy in follow-up biopsies and modification of immunosuppressive therapy can successfully prevent graft loss.

How Exercise Affects the Development and Progression of Hepatocellular Carcinoma by Changing the Biomolecular Status of the Tumor Microenvironment.

A sedentary lifestyle contributes to the development of nonalcoholic fatty liver disease. This disease is associated with hepatocellular carcinoma, even in the absence of cirrhosis. Nonalcoholic steatohepatitis mouse models have shown the benefits of regular exercise on hepatocellular carcinoma development. These models showed that total tumor volume per liver and tumor cell proliferation were reduced by exercise. Exercise also decreased the Ki-67-positive hepatocytes and increased p53 activity in the liver. In addition, an increased expression of Bcl-xL and the striking upregulation of p27 related to p53 activity were found in the liver. These findings suggest that p53 activation and resultant p27 expression are possible pathways by which exercise decreases hepatocyte proliferation and the development of tumor growth. Exercise could counteract hepatocellular carcinoma progression by activating adenosine monophosphate-activated protein kinase and thereby impairing mTORC1 activity. Impaired mTORC1 activity results in inhibition of cell proliferation in response to growth factors. The tumor suppressor PTEN was identified as a target of exercise by presenting increased expression in tumors of exercised rats. Loss of PTEN is shown to result in cell proliferation, growth, and invasion; therefore, increased expression of PTEN in a tumor will abate the cell proliferation and tumor growth. In addition, STAT3, a downstream factor of the mechanistic target of rapamycin that plays a role in tumor angiogenesis and metastasis, has been shown to be decreased in exercised rats. Thus, prevention of its activation will inhibit growth of hepatocellular carcinoma. In clinical studies, exercise was positively associated with improved recurrence-free survival in patients with hepatocellular carcinoma. Exercise may slow cancer progression by direct action on tumor-intrinsic factors and signaling pathways, thus possibly improving the efficacy of the anticancer treatment. This review explains the potential anticancer benefits of exercise by highlighting the tumor-intrinsic factors and signaling pathways of hepatocellular carcinoma associated with exercise.

Over 5 Years of Excellent Graft Kidney Function Determinants: Baskent University Experience.

OBJECTIVES: Kidney graft survival may be evaluated according to the duration of time with a functioning graft. Survival alone may not satisfy expectations of a successful kidney transplant if the graft kidney does not show excellent function. In our study, we analyzed the characteristics of kidney transplant recipients who showed excellent graft function after 5 to 10 years of follow-up in an aim to improve graft survival and to ensure the best kidney function in the long term. MATERIALS AND METHODS: We retrospectively evaluated graft function and demographic characteristics of 288 patients who underwent kidney transplant between January 2008 and December 2012. RESULTS: We found that 149 patients (51.7%) had excellent graft function, 88 patients (30.5%) had a functioning graft with a glomerular filtration rate lower than 60 mL/min and/or had signs of graft kidney dysfunction, and 45 patients (15.6%) experienced graft loss. Of 288 kidney transplant recipients enrolled in the study, most were male (56%), and mean age was 30.47 ± 14.36 years at time of transplant. Median time on dialysis was 39.09 ± 59.30 months. The overall graft survival rate in the patient group was 82.2% after 5 to 10 years of follow-up. Multivariate analysis showed that excellent graft survival predictors beyond 5 years were negative panel reactive antibody levels, lower donor age, shorter duration on dialysis, absence of acute rejection episodes, 3 or less HLA mismatches, lower immunosuppressive levels, and lower recipient age at transplant. CONCLUSIONS: Lower panel reactive antibody levels, lower donor age, shorter duration on dialysis, absence of acute rejection episodes, 3 or less HLA mismatches, and lower recipient age at transplant are major determinants of excellent graft survival in our kidney transplant recipients.

Quality of Life Through Gender Role Perspective in Candidate Renal Transplant Recipients: A Report From Baskent University Using the Short Form 36 Health Survey.

OBJECTIVES: The aim of the study was to evaluate the quality of life of patients with end-stage renal disease through a "gender role perspective." Patients were on hemodialysis treatment and on a wait list for transplant. MATERIALS AND METHODS: This study was conducted at the Baskent University Adana, Ankara, and Istanbul hemodialysis centers. Patients completed Short Form 36 Health Survey questionnaires voluntarily to evaluate quality of life. The questions were answered independently by patients while they were undergoing hemodialysis treatment. RESULTS: The mean age of participants was 54 ± 16.5 years. Quality of life was found to be higher in men (44.7 ± 19.2), and there was a negative correlation between quality of life and age in both sexes, as well as marriage age, number of pregnancies, and age of patient at the first live birth in women (P < .05). We found statistically significant differences between men and women regarding physical health and mental health dimensions. Quality of life scores increased with level of education (P < .001). In addition, patients in Ankara had the highest quality of life compared with Istanbul and Adana (P < .01). Average time on hemodialysis treatment, the number of weekly hemodialysis sessions, mean time of the disease, and mean duration of abandoning hemodialysis sessions were negatively associated with all components of quality of life (P < .05). CONCLUSIONS: We found that sex, education level, social status, and home city of patients had a high impact on quality of life. Thus, it is essential to educate both male and female patients regarding sex/gender and health issues before transplant to increase the recipient's physical and mental health dimensions.

Factors Predisposing to the Use of Complementary Therapies in Patients With Chronic Renal Failure.

OBJECTIVES: Our aim was to gather information about complementary medicine applications used by chronic renal failure patients and their relation to demographic factors. MATERIALS AND METHODS: Of 1750 chronic renal disease patients who were undergoing hemodialysis, only 450 patients attended in the study. Among 450 patients, 388 gave consent and were interviewed using a previously tested questionnaire. Questions about complementary and alternative medicine use, a list of commonly used methods, and the sources of knowledge about these were asked of all patients. RESULTS: We observed a significant difference in the patients who were using complementary and alternative medicines before and after diagnosis of chronic renal disease (P < .001). We noted that 87% of the patients used complementary and alternative medicines before diagnosis and 49.8% used these after diagnosis. Among the patients who used complementary and alternative medicines, 76% had faith in these therapies. Of patients who used complementary and alternative medicines, 95% believed that the remedies or processes used were beneficial to their health. Furthermore, 71% of users had great confidence in these therapies and had no belief that these could be harmful. Of those who used complementary and alternative therapies, 51% had no idea whether these therapies were harmful. The source of knowledge was mass media tools (47%), social life (friends, relatives, neighbors, colleagues; 45%), and other patients with chronic renal disease (8%). CONCLUSIONS: Complementary and alternative medicine therapies have a significant impact on patients with chronic renal disease. Doctors can warn patients about possible dangers of complementary and alternative medicine remedies and treatments.

Influence of Social, Economic, Familial, Marital Status, and Disease Adaptation on the Physical and Mental Health Dimensions of Patients Who Are Candidates for Renal Transplant.

OBJECTIVES: End-stage renal disease is a disease with a long duration, requiring patients to live with the limitations imposed by their condition. Stressors associated with this disease are demanding, with patients dependent on support from their social environment. Here, we aimed to show the influences of familial, social, economic, and marital status on quality of life in patients with end-stage renal disease. MATERIALS AND METHODS: Patients (190 women/188 men) who were under hemodialysis treatment and on transplant wait lists were included in the study. To evaluate the quality of life, patients completed the Short Form 36 health survey questionnaire voluntarily while undergoing hemodialysis treatment. All Short Form 36 questionnaire components were analyzed separately, and all social, economic, and business life dimensions were examined with another questionnaire. RESULTS: Significant differences were observed between single and married patients regarding physical and mental health dimensions (P < .001), with quality of life higher in single patients than in married. Patients who lived in villages had lower health quality than patients who resided in cities or towns (P < .01). Patients who were home owners and who had a job had higher degrees of health quality than those who did not (P < .01). The lowest Short Form 36 scores were in housewives and farmers (P < .001). Comparisons between patients who went home after hemodialysis versus those who went to work showed better Short Form 36 scores in working patients (P < .001). Patients with private insurance and family support had better Short Form 36 scores (P < .001). Patients who did not comply with their doctor and dietician showed the lowest health quality (P < .05). Regular or irregular drug use did not affect scores. CONCLUSIONS: Familial, social, economic, and marital statuses, in addition to the influence of disease adaptation, independently affected the well-being of patients with end-stage renal disease.

Intracoronary versus intravenous high-dose bolus plus maintenance administration of tirofiban in patients undergoing primary percutaneous coronary intervention for acute ST elevation myocardial infarction.

We aimed to examine whether intracoronary high-dose bolus of tirofiban plus maintenance would result in improved clinical outcome in STEMI patients undergoing primary PCI in this pilot trial. A total of 56 patients were enrolled to receive either intracoronary high-dose bolus plus maintenance (n = 34) or intravenous high-dose bolus plus maintenance (n = 22) of tirofiban. Pre and post intervention TIMI flow grades, myocardial blush grades, peak CKMB and troponin levels, time to peak CKMB and troponin, time to 50% ST resolution and major composite adverse cardiac event rates at 30 days were recorded. Although incidence of major adverse cardiac events was not different, post intervention TIMI flow and TIMI blush grades, peak CKMB and troponin levels, and time to peak CKMB and time to peak troponin were significantly different, favoring intracoronary strategy. In conclusion, this regimen improved myocardial reperfusion and coronary flow, and reduced myocardial necrosis, but failed to improve clinical outcomes at 30 days.

Evaluation of acute infection-induced endothelial dysfunction and its potential mediators.

OBJECTIVES: Inflammation plays an important role in the pathophysiology of atherosclerosis. Some studies suggest a link between chronic infections, an inflammatory state, and endothelial dysfunction. However, data related to acute infections are scant. We have investigated: (i) the effect of acute infection on endothelial function; (ii) the role of potential mediators of endothelial dysfunction. METHODS: Forty patients 40 years old with acute infection (mean age 53.9 +/- 8.8 years), without coronary artery disease or its equivalents were enrolled. Endothelial function and blood levels of high sensitive C-reactive protein, interleukin-6, tumour necrosis factor-a, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), apolipoprotein-A1 (Apo-A1) and apolipoprotein-B100 (Apo-B100) were assessed in the acute infection phase and 1 month after recovery. Endothelial function was evaluated by brachial artery flow-mediated vasodilation (FMD). RESULTS: The intraclass correlation coefficients for intra- and interobserver agreement for FMD measurements were 0.98 (95% CI: 0.95-0.99) and 0.93 (95% CI: 0.83-0.97), respectively. FMD improved significantly 1 month after recovery (P < 0.001). Compared to the levels at 1 month, inflammatory markers, LDL cholesterol, LDL/HDL ratio, Apo-B100 and Apo-B100/Apo-A1 ratio were significantly higher. However, HDL and apo-A1 were significantly lower in the phase of acute infection. Change in FMD from baseline to 1 month after recovery correlated significantly only with the change in Apo-A1 (r = 0.35, P = 0.027). CONCLUSIONS: Acute infection causes transient endothelial dysfunction. It increases inflammatory markers and generates an atherogenic lipid profile. Among the parameters evaluated, only the change in Apo-A1 level was associated with acute infection-induced endothelial dysfunction.

[Percutaneous treatment of Lutembacher syndrome: a case report]. / Lutembacher sendromlu bir olguda perkütan tedavi.

Lutembacher syndrome is a rare combination of congenital atrial septal defect (ASD) and acquired mitral stenosis (MS). Although it is traditionally corrected by surgical treatment, both conditions are amenable to transcatheter treatment without the need for surgery. We present a 49-year-old woman with Lutembacher syndrome. On pretreatment transthoracic echocardiography, planimetric mitral valve area was 1.5 cm(2), maximum diastolic gradient was 17 mmHg, and mean diastolic gradient was 9 mmHg. Combined percutaneous treatment was performed including balloon valvuloplasty for MS and closure of the ASD with the Amplatzer septal occluder. The patient was discharged uneventfully. Transthoracic echocardiography performed a week later showed planimetric mitral valve area as 2.1 cm(2), maximum diastolic gradient as 9 mmHg, and mean diastolic gradient as 4 mmHg. Complete closure of the ASD was achieved. Transcatheter treatment may be an effective alternative to surgery in selected patients with Lutembacher syndrome.

Prediction of subclinical left ventricular dysfunction with longitudinal two-dimensional strain and strain rate imaging in patients with mitral stenosis.

Longitudinal two-dimensional strain deformation is a novel technique which evaluates global and regional left ventricular (LV) function with high reproducibility. The aim of the study was to investigate the global and regional systolic function using this method in patients with pure mitral stenosis (MS). Conventional echocardiography and longitudinal two-dimensional strain analysis were performed in 60 patients (41 +/- 5 years, 48 women) with mild to moderate MS (mitral valve area: 1.9 +/- 0.5 cm(2)), and 52 healthy controls (40 +/- 7 years, 37 women). For strain analysis standard apical views were obtained, and by using a software system peak systolic strain and strain rate were calculated off-line in each segment. In all, 88% of the segments could be optimally tracked by the software system. Despite normal LV systolic function as assessed by ejection fraction (66 +/- 8%), mean global longitudinal strain (GLS) and global longitudinal strain rate (GLSR) were significantly reduced in patients with isolated MS (GLS -17 +/- 3.3 vs. -19 +/- 2.5%, P = 0.006 and GLSR -1.3 +/- 0.3 vs. -1.5 +/- 0.3 s(-1), P < 0.0001). Regional analysis demonstrated that patients with MS had a significantly reduced longitudinal peak strain and strain rate in all basal, and some mid (inferior, anteroseptal, interventricular septum) segments of the left ventricle. For other segments longitudinal peak strain and strain rate values were similar among the groups. Evaluation of LV systolic function by longitudinal two-dimensional strain deformation identified early abnormalities in MS patients who had apparently normal standard systolic function.

Two-dimensional longitudinal strain and strain rate imaging for assessing the right ventricular function in patients with mitral stenosis.

BACKGROUND: Longitudinal two-dimensional strain (L2DS) deformation is a novel technique that evaluates global and regional right ventricular (RV) function. The aim of the study was to investigate the systolic function of RV by using this method in patients with pure mitral stenosis (MS). METHODS: Conventional echocardiography and L2DS analysis were performed in 45 MS patients and 21 healthy controls. For strain analysis apical four-chamber views were obtained and by using a software system, peak systolic strain and strain rates were calculated off-line in each segment. RESULTS: The mean global longitudinal strain (GLS) of the whole RV (-20 + or - 7 vs. -24 + or - 6%, P= 0.02) and mean GLS of the septum (-19 + or - 7 vs. -23 + or - 5%, P = 0.03) were significantly reduced in the MS patients. Compared with the control group no significant change was determined in the mean GLS of the RV free wall (RVFW). While the mean global longitudinal strain rates (GLSR) of the entire RV and RVFW were similar between the groups, a significant difference in the mean GLSR of the septum (-1.2 + or - 0.4 vs. -1.5 + or - 0.3 s(-1), P= 0.005) was determined in the patients with MS. A regional analysis demonstrated that MS patients had significantly reduced strain and strain rates in the basal and mid-segments of the septum, whereas only lower strain values in the basal RVFW. CONCLUSIONS: RV systolic function evaluated by L2DS analysis in patients with MS has shown decreased global and segmental systolic functions. (ECHOCARDIOGRAPHY 2010;27:525-533).

Very late drug-eluting stent thrombosis in a patient with an INR of 4.4.

Duration of dual antiplatelet therapy after drug-eluting stent implantation is still an important issue awaiting a definite answer. A 50-year-old male patient was admitted with acute-onset chest pain and was diagnosed to have acute anterior myocardial infarction due to very late stent thrombosis. He had a 38-month history of two sirolimus-eluting stent implantation in the proximal left anterior descending (LAD) coronary artery. He had been on warfarin along with clopidogrel 75 mg/day until he decided to cease clopidogrel before a minor dental procedure 10 days before. Findings of physical examination and laboratory tests were normal except for an INR value of 4.4. After a loading dose of 300 mg clopidogrel, he was immediately taken to the catheterization laboratory. Angiography of the left system showed total occlusion of the proximal LAD with a thrombus at the level of the proximal stent. He was successfully revascularized without any complication and was discharged free of symptoms.

The relation between endothelial dependent flow mediated dilation of the brachial artery and coronary collateral development - a cross sectional study.

BACKGROUND: Endothelial dysfunction is thought to be a potential mechanism for the decreased presence of coronary collaterals. The aim of the study was to investigate the association between systemic endothelial function and the extent of coronary collaterals. METHODS: We investigated the association between endothelial function assessed via flow mediated dilation (FMD) of the brachial artery following reactive hyperemia and the extent of coronary collaterals graded from 0 to 3 according to Rentrop classification in a cohort of 171 consecutive patients who had high grade coronary stenosis or occlusion on their angiograms. RESULTS: Mean age was 61 years and 75% were males. Of the 171 patients 88 (51%) had well developed collaterals (grades of 2 or 3) whereas 83 (49%) had impaired collateral development (grades of 0 or 1). Patients with poor collaterals were significantly more likely to have diabetes (p = 0.001), but less likely to have used statins (p = 0.083). FMD measurements were not significantly different among good and poor collateral groups (11.5 +/- 5.6 vs. 10.4 +/- 6.2% respectively, p = 0.214). Nitroglycerin mediated dilation was also similar (13.4 +/- 5.9 vs. 12.8 +/- 6.5%, p = 0.521). CONCLUSION: No significant association was found between the extent of angiographically visible coronary collaterals and systemic endothelial function assessed by FMD of the brachial artery.

Changing patterns of patient characteristics in the cath lab from 1998 to 2006: a single-centre retrospective analysis.

BACKGROUND: There are few data on the change in the profile of cath lab patients over long time intervals. METHODS: We retrospectively analysed our cath lab records, patient charts, in terms of demographic variables, clinical and laboratory characteristics in a thousand patients (499 patients in 1998 January-March, 501 patients in 2006 January-March). RESULTS: Mean age was significantly higher in the 2006 cohort (57.5 +/- 11 vs. 62.2 +/- 10.8, P < 0.001). Gender was similar in both cohorts (men 68.5% vs. women 69.9%, P = 0.65). Both hypertension and diabetes mellitus were more prevalent in the 2006 cohort (613% vs. 49.3 and 30.3 vs. 17.6 respectively, P < 0.001 for both). Smoking rates (past or active) did not differ between the cohorts. Rates of normal or near normal coronary angiograms were somewhat elevated in both cohorts (36.7% in 1998 and 39.1% in 2006). Rates of multivessel disease (2-3 vessel disease) tended to increase and rates of single-vessel disease tended to decrease from the 1998 cohort to the 2006 cohort (27.7% to 34.4% and 35.7% to 26.7%, P = 0.006). The number of percutaneous coronary interventions (PCI) performed increased with a borderline statistical significance in the 2006 cohort (32% vs. 38.5%, P = 0.053). CONCLUSIONS: Our data indicates that today interventional cardiologists face an older and more severely diseased cath lab patient population compared with a decade earlier. In comparison with 1998, more PCIs were performed.

The impact of the distance between the atrial electrode and the atrial wall on atrial undersensing in patients with VDD pacemakers: long-term follow-up.

AIM: Atrial undersensing (AUS) in single-lead VDD pacemakers may be due to diminished P-wave amplitude secondary to local inflammation beneath the electrodes closer to atrial wall. The aim of this study was to assess the potential effect of distance between atrial electrode and atrial wall on immediate and long-term atrial sensing stability in VDD systems. METHODS: A total of 275 patients with normal sinus node function who received VDD pacemakers were enrolled into the study and were followed up for a median duration of 33 months. During each control visit, a standard 12-lead electrocardiogram (ECG) was obtained and standard pacemaker function assessment was performed including testing for pacing threshold and atrioventricular synchrony. The distance between atrial electrode and atrial wall was measured from chest X-ray. RESULTS: Of the 275 patients, AUS was detected in 59 patients. Univariate predictors of AUS were use of closely spaced bipolar ring atrial electrode (CSBR) (P = 0.01), wider atrial ring-spacing (P = 0.03), and atrial sensitivity programmed to a higher level (P = 0.001). Use of CSBR (P = 0.04) and atrial sensitivity > or =0.3 mV (P = 0.02) were observed to be the independent predictors for AUS. When the distance between atrial electrode and atrial wall was <7 mm, AUS was less with diagonally arranged bipolar ring electrodes (DABR) than it was with CSBRs (P = 0.02). CONCLUSIONS: The distance between atrial electrode and atrial wall does not appear to affect AUS incidence in VDD pacemakers. For VDD electrodes closer to atrial wall, AUS was significantly less likely in DABR-type electrodes.

The effect of high-dose aspirin pre-treatment on the incidence of myonecrosis following elective coronary stenting.

BACKGROUND: Inadequate platelet response to aspirin is associated with increased incidence of peri-procedural myonecrosis. Antiplatelet activity of aspirin can be improved by increasing the dose. High-dose aspirin pre-treatment, therefore, may reduce the incidence of myonecrosis post stenting. METHODS AND RESULTS: Two-hundred patients taking 75-325 mg daily doses of aspirin for at least 2 weeks were randomized for addition or no addition of 500 mg aspirin before elective coronary stenting (aspirin 500 group, n=100 and control group, n=100). Primary endpoint was the occurrence of peri-procedural myonecrosis defined as creatine kinase-myocardial band (CK-MB) elevation of >1x upper limits of normal (ULN). Aspirin 500 patients were significantly younger and more likely to have family history of coronary artery disease, but less likely to have received statins than controls. Elevation of CK-MB was observed in 29% of aspirin 500 patients and 15% of controls (p=0.017). The incidence of non-Q wave myocardial infarction (CK-MB elevation of >3xULN) tended to be higher in the aspirin 500 group than in the control group (5% versus 0%, p=0.059). Multivariate analysis identified baseline aspirin dose (OR: 1.006; 95% CI: 1.002-1.010; p=0.004), aspirin 500 mg treatment (OR: 2.5; 95% CI: 1.2-5.5; p=0.021) and baseline CK-MB level (OR: 1.4; 95% CI: 1.1-1.7; p=0.012) as independent predictors of CK-MB elevation after coronary stenting. CONCLUSION: For patients taking daily low-dose aspirin therapy, supplementation with high-dose aspirin before elective coronary stenting does not reduce, but may increase the incidence of peri-procedural myonecrosis.

Glu298Asp polymorphism of the eNOS gene is associated with coronary collateral development.

OBJECTIVE: We examined the endothelial nitric oxide (eNOS) gene Glu298Asp polymorphism to assess its possible association with the extent of coronary collaterals. METHODS: A total of 473 consecutive patients who had high grade coronary stenosis or occlusion were evaluated for the extent of coronary collaterals by using Rentrop classification. Patients with grade 0 or 1 collaterals were identified as having poor collaterals. The relation between collateral status and eNOS Glu298Asp polymorphism was studied by multivariate logistic regression analysis. RESULTS: Subjects with poor collaterals were more likely to have diabetes mellitus (p<0.001) and unstable angina pectoris as clinical presentation (p=0.014) and more likely to carry Asp298 variant (p=0.02) but they were less likely to have received statins (p=0.031). Multivariate analysis demonstrated that Asp298 allele carriers were 1.7 times more likely to have poor collaterals than patients with GluGlu genotype (95% CI: 1.09-2.69, p=0.024). There was a significant interaction between diabetes mellitus and eNOS Glu298Asp polymorphism in the analysis of collateral development. Among 145 diabetic patients Asp298 allele was the only predictor of poor collateral development with OR of 5.38 (95% CI: 2.41-11.98, p<0.001). Once diabetic patients were excluded from the analysis Asp298 allele was no longer a significant correlate of poor collateral formation. CONCLUSIONS: The present study suggests that the Asp298 allele of the eNOS gene is significantly associated with impaired collateral development, especially in patients with diabetes mellitus. Treatment strategies that modulate eNOS activity and/or NO production may improve coronary collateral development.

Angiographic evaluation of myocardial perfusion in patients with syndrome X.

We evaluated tissue level perfusion in patients who had syndrome X using the myocardial blush grade technique. Normal tissue perfusion in all coronary territories was observed in 23 patients (41.8%) who had syndrome X and in 44 control subjects (80%). Total myocardial blush score (sum of the myocardial blush grades of each coronary territory) was significantly lower in patients who had syndrome X than in control subjects (8.2 +/- 0.7 vs 8.7 +/- 0.5, p <0.0001). We have demonstrated for the first time that a substantial number of patients who have syndrome X have impaired tissue level perfusion, and this might be assumed as a surrogate marker of a diseased microvascular network in the catheterization laboratory.

A safe and simple method for management of frozen pacemaker leads.

The traction of frozen leads from the generator header is difficult in some patients. This report describes the authors' experience with frozen leads in which the lead pins were removed by pushing with the tip of screwdriver from the hole created with a scalpel blade at the closed end of the generator header.