Athanassios Manginas

Ascorbic Acid Prevents Contrast-Mediated Nephropathy in Patients With Renal Dysfunction Undergoing Coronary Angiography or Intervention

Background—Contrast agents can cause a reduction in renal function that may be due to the generation of reactive oxygen species. Conflicting evidence suggests that administration of the antioxidant acetylcysteine prevents this renal impairment. The action of other antioxidant agents has not been investigated. Methods and Results—We conducted a randomized, double-blind, placebo-controlled trial of ascorbic acid in 231 patients with a serum creatinine concentration ≥1.2 mg/dL who underwent coronary angiography and/or intervention. Ascorbic acid, 3 g at least 2 hours before the procedure and 2 g in the night and the morning after the procedure, or placebo was administered orally. Contrast-mediated nephropathy was defined by an absolute increase of serum creatinine ≥0.5 mg/dL or a relative increase of ≥25% measured 2 to 5 days after the procedure. Contrast-mediated nephropathy occurred in 11 of the 118 patients (9%) in the ascorbic acid group and in 23 of the 113 patients (20%) in the placebo group (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.17 to 0.85; P=0.02). The mean serum creatinine concentration increased significantly in the placebo group (from 1.36±0.50 to 1.50±0.54 mg/dL, P<0.001) and nonsignificantly in the ascorbic acid group (from 1.46±0.52 to 1.52±0.64 mg/dL, P=0.07). The mean increase in serum creatinine concentration was greater in the placebo group than in the ascorbic acid group (difference of 0.09 mg/dL; 95% CI, 0.00 to 0.17; P=0.049). Conclusions—Prophylactic oral administration of ascorbic acid may protect against contrast-mediated nephropathy in high-risk patients undergoing a coronary procedure.

Prognostic significance of echocardiographically estimated right ventricular shortening in advanced heart failure

Little is known about the association of echocardiographic estimates of right ventricular (RV) function with survival, in relation to hemodynamic and exercise-derived predictors of outcome in congestive heart failure. We prospectively studied 40 patients (age 55+/-10 years, in New York Heart Association functional class III [70%] and IV [30%]), with left ventricular (LV) ejection fraction <30%. At enrollment, all patients underwent echocardiographic evaluation of LV dimensions and function. RV shortening was measured as the difference of the end-diastolic distance - the end-systolic distance between the tricuspid annulus and the RV apex. Thirty-five patients (88%) were able to perform a maximal symptom-limited exercise test. Peak oxygen consumption (peak VO2) and percent peak age- and gender-adjusted predicted oxygen consumption (%peak VO2) were calculated. Of 40 patients, 10 died during a mean follow-up period of 14+/-10 months. On univariate analysis, nonsurvivors had lower RV shortening (p=0.0001), higher pulmonary artery wedge pressure (p=0.009), higher pulmonary vascular resistance (p=0.02), and lower mean aortic pressure (p=0.05). Cox proportional-hazards model revealed that the only independent associate of survival was RV shortening (p=0.0005), with a trend toward significance for mean aortic pressure (p=0.08). The best cutoff point of RV shortening identified by the receiver-operating curve was 1.25 cm. This value had a sensitivity of 90%, specificity of 80%, and overall predictive accuracy of 83% to distinguish survivors from nonsurvivors. In patients with advanced heart failure, preserved RV function as indicated by an echocardiographically derived RV shortening > 1.25 cm is a strong predictor of survival.

Estimation of coronary flow reserve using the Thrombolysis In Myocardial Infarction (TIMI) frame count method

A simple and readily available method of estimating coronary flow velocity reserve may have significant clinical value. With use of intracoronary adenosine we documented a very good correlation between coronary flow reserve values obtained with the Thrombolysis In Myocardial Infarction trial frame count method and the invasive Doppler wire (Flowire) technique.

Intracoronary Infusion of CD133+ and CD133−CD34+ Selected Autologous Bone Marrow Progenitor Cells in Patients with Chronic Ischemic Cardiomyopathy: Cell Isolation, Adherence to the Infarcted Area, and Body Distribution

Central issues in intracoronary infusion (ICI) of bone marrow (BM)‐cells to damaged myocardium for improving cardiac function are the cell number that is feasible and safe to be administrated as well as the retention of cells in the target area. Our study addressed these issues in eight patients with chronic ischemic cardiomyopathy undergoing ICI of selected BM‐progenitors. We could immunomagnetically isolate 0.8 ± 0.32 × 107 CD133+ cells and 0.75 ± 0.24 × 107 CD133−CD34+ cells from 310 ± 40 ml BM. After labeling these cells with 99mTc‐hexamethylpropylenamineoxime, they were infused into the infarct‐related artery without any complication. Scintigraphic images 1 (eight patients) and 24 hours (four patients) after ICI revealed an uptake of 9.2% ± 3.6 and 6.8% ± 2.4 of the total infused radioactivity in the infarcted area of the heart, respectively; the remaining activity was distributed mainly to liver and spleen. We conclude that through ICI of CD133+ and CD133−CD34+ BM‐progenitors a significant number of them are preferentially attracted to and retained in the chronic ischemic myocardium.

Pilot study to evaluate the safety and feasibility of intracoronary CD133(+) and CD133(-) CD34(+) cell therapy in patients with nonviable anterior myocardial infarction.

Objectives: The long‐term effect of intracoronary infusion of progenitor cells in patients with chronic ischemic cardiomyopathy. Background: Bone marrow stem‐cell administration in patients with myocardial infarction improved myocardial performance and in some studies contributed to favorable left ventricular remodeling. Methods: We report on the results of a pilot, single center, controlled safety, and feasibility study, including 24 patients with old, nonviable anterior myocardial infarction. Twelve patients underwent intracoronary administration of selected CD133+ and CD133−CD34+ progenitor cells and 12 were followed up on medical therapy. Left ventricular volumes and ejection fraction, at rest and during low‐dose dobutamine, and myocardial viability, using TL‐201 reinjection scintigraphy, were analyzed at baseline and long‐term follow‐up. Results: Patients in the treatment group experienced a sustained decrease in left ventricular end‐diastolic and end‐systolic resting volumes (P = 0.008 and P = 0.002, respectively), as well as an improvement in global ejection fraction at rest [from (27.2 ± 6.8)% to (29.7 ± 7.3)%, P = 0.016]. Segmental anterior and apical wall perfusion, during TL‐201 reinjection, were similarly improved (P = 0.005 and P << 0.001, respectively). One patient developed restenosis at the cell delivery site and one progression of atherosclerosis. During 28.0 ± 8.7 months of clinical follow‐up, only one patient experienced deterioration of heart failure. In the control group, we observed stability in the perfusion defect and deterioration in end‐diastolic and end‐systolic volumes (P= 0.002 and P = 0.003, respectively) and a nonsignificant decrease in ejection fraction (P = 0.11). Conclusion: Intracoronary infusion of selected CD133+ and CD133−CD34+ progenitor cells to a previously infarcted and nonviable anterior wall is safe, and results in sustained improvement in segmental myocardial perfusion and in favorable left ventricular remodeling.

Benefits of physical training on exercise capacity, inspiratory muscle function, and quality of life in patients with ventricular assist devices long-term postimplantation

Background: Capacity to exercise may not be fully restored in patients with heart failure even in the long term after ventricular assist device (VAD) implantation. The benefits of exercise training in patients with VAD are unknown. Design and methods: Fifteen patients, aged 38.3 ± 15.9 years, bridged to heart transplantation with left ventricular assist device or biventricular assist device were randomized at a ratio of 2 : 1 to a training group (TG, n = 10) or a control group (n = 5), 6.3 ± 4 months after implantation. Both the groups were advised to walk 30–45 min/day. TG also underwent moderate-intensity aerobic exercise using a bike or treadmill for 45 min, three to five times a week, combined with high-intensity inspiratory muscle training using a computer-designed software to respiratory exhaustion, two to three times a week for 10 weeks. The patients were tested using cardiopulmonary exercise testing, 6-min walk test, spirometry and electronic pressure manometer for inspiratory muscle strength (Pimax) and endurance (sustained Pimax) measurement. Quality of life was assessed with the Minnesota Living with Heart Failure questionnaire. Results: TG improved peak oxygen consumption (19.3 ± 4.5 vs. 16.8 ± 3.7 ml/kg per min, P = 0.008) and VO2 at ventilatory threshold (15.1 ± 4.2 vs. 12 ± 5.6 ml/kg per min, P = 0.01), whereas the ventilation/carbon dioxide slope decreased (35.9 ± 5.6 vs. 40 ± 6.5, P = 0.009). The 6-min walk test distance increased (527 ± 76 vs. 462 ± 88 m, P = 0.005) and quality of life was improved (38.2 ± 11.6 vs. 48.9 ± 12.8, P = 0.005), as well as Pimax (131.8 ± 33 vs. 95.5 ± 28cmH2O, P = 0.005), sustained Pimax (484 ± 195 vs. 340 ± 193cmH2O/s/10 3 , P = 0.005), and inspiratoty lung capacity (2.4 ± 0.9 vs. 1.7 ± 0.7 L, P = 0.008) were improved. No significant changes were noted in the control group. Conclusion: Our findings indicate that exercise training may improve the functional status of VAD recipients even at a later period after implantation and thus, may have additional importance in cases of destination therapy.

Effect of the oral endothelin antagonist bosentan on the clinical, exercise, and haemodynamic status of patients with pulmonary arterial hypertension related to congenital heart disease

Objective: To evaluate the clinical, exercise, and haemodynamic effects of chronic oral administration of the non-selective endothelin receptor antagonist bosentan on patients with pulmonary arterial hypertension (PAH) related to congenital heart disease (CHD). Design: Prospective non-randomised open clinical study. Setting: Cardiology tertiary referral centre. Patients: 21 patients with a mean (SEM) age of 22 (3) years with chronic PAH related to CHD (15 with Eisenmenger’s syndrome). Patients were in World Health Organization (WHO) class II to IV with oxygen saturation 87 (2)%. Intervention: Patients underwent clinical, exercise, and haemodynamic evaluations at baseline and after 16 weeks of treatment. Results: Bosentan improved (p < 0.01) WHO class, peak oxygen consumption from 16.8 (1.4) to 18.3 (1.4) ml/kg/min, exercise duration from 9.0 (0.8) to 10.7 (0.6) minutes during the treadmill test, walking distance from 416 (23) to 459 (22) m, and Borg dyspnoea index from 2.8 (0.2) to 2.0 (0.1) during the six minute walk test. Bosentan treatment improved (p < 0.05) mean pulmonary artery pressure from 87 (4) to 81 (4) mm Hg, pulmonary blood flow index from 3.2 (0.4) to 3.7 (0.5) l/min/m2, pulmonary to systemic blood flow ratio from 1.2 (0.2) to 1.4 (0.2), and pulmonary vascular resistance index from 2232 (283) to 1768 (248) dyn·s·cm−5. Two patients died, presumably of arrhythmic causes, who were in WHO class IV at baseline and who had improved during treatment. Conclusions: Bosentan induces short and mid term clinical, exercise, and haemodynamic improvements in patients with PAH related to CHD. Larger studies with long term endothelin receptor antagonism are needed to assess the safety and possible treatment role of bosentan in this population.

Immune response to inspiratory muscle training in patients with chronic heart failure.

Background The effects of inspiratory muscle training on plasma cytokines, C-reactive protein and the soluble apoptosis mediators Fas and Fas ligand in chronic heart failure are unknown. Design and methods Thirty-eight patients with chronic heart failure, age 57 ± 2 years, New York Heart Association classification II-III, were assigned to either a high intensity training group (n = 15, age 53±2 years) exercised at 60% of sustained maximal inspiratory pressure, or a low intensity training group (n = 23, age 59 ± 2 years), exercised at 15% of sustained maximal inspiratory pressure, three times per week for 10 weeks. Patients in the high intensity training group and low intensity training group were matched for age, sex and New York Heart Association functional class. Plasma levels of tumor necrosis factor (TNF)-α, soluble TNF receptor I, interleukin-6, C-reactive protein, soluble apoptosis mediators Fas and Fas ligand were measured at baseline and at post-inspiratory muscle training. Pulmonary function was assessed by spirometry, exercise capacity by a cardiopulmonary exercise test and the 6 min walk test, whereas dyspnea by the Borg scale after the 6 min walk test. Results High intensity training group improved inspiratory muscle strength (105.1 ± 4.9 vs. 79.8 ± 4.7 cmH2O, P < 0.001), sustained maximal inspiratory pressure (504.5 ± 39.7 vs. 312.5 ± 26.5cmH2O/s/103, P<0.001), forced vital capacity (98.9 ± 3.9 vs. 96 ± 3.3%, P<0.05), peak Vo2 (19.4 ± 1.2 vs. 17.3 ± 0.9 ml/kg per min, P<0.01), 6 min walk test distance (404.3 ± 11.9 vs. 378.2 ± 10.4 m, P<0.01) and dyspnea (8.0 ± 0.4 vs. 9.2 ± 0.4, P<0.01). Circulating TNF-α, soluble TNF receptor I, interleukin-6, C-reactive protein, soluble apoptosis mediators Fas and Fas ligand were not significantly altered. Low intensity training group increased only the inspiratory muscle strength (90.3 ± 5.9 vs. 80.2 ± 5cmH2O, P<0.01). Comparison between groups was significant for soluble TNF receptor I change (high intensity training group, 5.8 ± 0.49 vs. 6.1 ± 0.42; low intensity training group, 8.4 ± 0.6 vs. 7.8 ± 0.6, P<0.01). Conclusion A high intensity inspiratory muscle training program resulted in improvement in functional status of chronic heart failure patients compared with low intensity inspiratory muscle training. Improvement in exercise capacity was not associated with an anti-inflammatory effect, although a beneficial influence on soluble TNF receptor I was recorded. Possible reasons include inadequate level of muscle mass exercise and the low pretraining New York Heart Association class. Eur J Cardiovasc Prev Rehabil 14:679-685

Inflammatory cytokine gene variants in coronary artery disease patients in Greece.

ObjectiveAbundant evidence supports the central role of inflammatory cytokines in immune responses mediating the pathogenesis of atherosclerosis, coronary artery disease, and its complications, such as myocardial infarction and unstable angina. MethodsWe investigated the association of genetic polymorphisms of the inflammatory cytokines, IL-10, TGF-&bgr;1, IFN-&ggr;, IL-6, and TNF-&agr; with the clinical presentation of coronary artery disease in 26 patients with stable angina, 45 patients with unstable angina and 58 patients who had experienced nonfatal myocardial infarction. Genotyping was performed by the sequence-specific primer polymerase chain reaction method. ResultsA significant difference in the frequencies of -174G/C IL-6 alleles was observed, with the low in-vitro producing -174*C allele predominating in patients with myocardial infarction, compared with stable angina and unstable angina patients, after the analysis of genotypes (P=0.024 and 0.022, respectively), phenotypes [P=0.0099, odds ratio (OR)=0.271, 95% confidence interval (CI)=0.1012–0.7292; P=0.03, OR=0.40, respectively] and haplotypes (P=0.007, OR=3.028, 95% CI=1.347–6.806; P=0.0096, OR=2.368, 95% CI=1.262–4.444; respectively). In addition, a predominance of the -1082ACC/ATA IL-10 genotype in the myocardial infarction group compared with the unstable angina group and the -874 A/A IFN-&ggr; genotype in the stable angina group compared with the unstable angina and the myocardial infarction group, was found. No significant differences in the distribution of genotypes, phenotypes and haplotypes in the three study groups, for the TNF-&agr;-308 A/G and TGF-&bgr;1-codon 25 G/C, codon 10 T/C polymorphisms were detected. ConclusionOur data provide evidence that the IL-6-174G/C polymorphism may be involved in the pathogenesis of coronary artery disease, contributing to genetic susceptibility for myocardial infarction.

Prediction of Restenosis After Coronary Angioplasty by Use of a New Index TIMI Frame Count/Minimal Luminal Diameter Ratio

BACKGROUND It has been shown recently that postangioplasty coronary flow reserve and the degree of residual stenosis have a modest predictive value for short- and long-term clinical outcomes after coronary angioplasty. Corrected TIMI frame count (CTFC) is a simple quantitative index of coronary blood flow. Its relationship with Doppler coronary flow velocity and clinical outcome after coronary angioplasty has not been fully clarified. The aim of this study was to identify clinical, angiographic, and functional predictors of clinical and angiographic restenosis after conventional coronary angioplasty. METHODS AND RESULTS We studied 70 consecutive patients in whom intracoronary Doppler flow-velocity measurements were performed before and after angioplasty. Patients were evaluated for restenosis by clinical follow-up, exercise stress test/(201)Tl scintigraphy, and follow-up angiography, which was performed at 10. 5+/-10.3 months in 63 patients. According to the results of univariate analysis, a new index, postangioplasty CTFC/minimal luminal diameter (MLD) ratio, was created. Multivariate analysis revealed that CTFC/MLD ratio was the only independent predictor of angiographic (OR 2.02; 95% CI 1.37 to 2.97; P<0.0004) and clinical (OR 1.60; 95% CI 1.15 to 2.21; P<0.005) restenosis. The receiver operating characteristic curve area of this index was 79% for angiographic and 73% for clinical restenosis. The optimal CTFC/MLD ratio cutoff values were 7.88 for angiographic and 7.94 for clinical restenosis, respectively. CONCLUSIONS Our data indicate that postangioplasty CTFC/MLD ratio, which incorporates both the angiographic and functional features of coronary lesions, is a reliable, objective, and inexpensive index for prediction of angiographic and clinical restenosis after conventional coronary angioplasty.