Can microvolt T-wave alternans testing reduce unnecessary defibrillator implantation?

The Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) have established that patients with a reduced ejection fraction gain an overall mortality benefit from prophylactic implantable cardioverter-defibrillator therapy. Only a small proportion of the patients in these studies, however, have received life-saving therapy from the defibrillator. Because defibrillator therapy is invasive and expensive, patients with a low ejection fraction would benefit from effective risk stratification so that defibrillator therapy was used only in those at significant risk. In this review, we analyze prospective clinical trials that have evaluated microvolt T-wave alternans (MTWA) testing as a predictor of ventricular tachyarrhythmic events in populations of patients similar to those studied in MADIT II or SCD-HeFT; that is, patients with a reduced ejection fraction who were not selected on the basis of a history of ventricular tachyarrhythmias. In these studies, the average annual rate of fatal and nonfatal ventricular tachyarrhythmic events among the patients who tested negative for MTWA was around 1%. This rate is so low that it is unlikely that such patients would benefit from implantable cardioverter-defibrillator therapy. The mortality, moreover, was lower among MTWA-negative patients who did not receive implantable defibrillators than that observed in the MADIT II and SCD-HeFT patients who received implantable cardioverter-defibrillators. In response, patients with a low ejection fraction who are being considered for implantable cardioverter-defibrillator therapy should undergo MTWA testing as part of their evaluation.     

Predictors of endothelial dysfunction in young women with polycystic ovary syndrome

CONTEXT: Women with polycystic ovary syndrome (PCOS) may be at increased risk for cardiovascular disease. Endothelial dysfunction is an early marker of atherosclerosis. OBJECTIVES: The objectives of this study were to 1) compare endothelial function in young women with PCOS and regularly menstruating control women, and 2) to identify the determinants of endothelial function and investigate its relationship with body mass index in women with PCOS. DESIGN: This was a cross-sectional study. SETTING: This study was conducted at a tertiary cardiovascular research center. PATIENTS: Sixty-two young women with PCOS (mean age, 22.7 yr) and 17 control women, matched as a group for age and body mass index, were studied. Twenty-three women with PCOS were lean, 21 were overweight, and 18 were obese. MAIN OUTCOME MEASURES: Endothelium-dependent and -independent vascular function was assessed by measuring flow-mediated dilation (FMD) and nitrate-mediated dilation in the brachial artery (diameter change during hand hyperemia and after sublingual glyceryl trinitrate administration, respectively). RESULTS: FMD and nitrate-mediated dilation were significantly lower in PCOS than in control women (reduced by approximately 50 and 25%, respectively; both P < 0.0005). Insulin resistance, total testosterone, and total cholesterol were independent predictors of FMD, accounting for 21, 10, and 9% of the variance, respectively (P < 0.005 for all). A trend of deterioration in FMD from lean to overweight and obese PCOS women was observed, but differences among groups were not statistically significant. CONCLUSIONS: Women with PCOS have significant endothelial dysfunction at an early age (i.e. early 20s), and largely independent of obesity. This suggests that women with PCOS are at increased risk for early onset cardiovascular disease and may gain particular benefit from measures to improve endothelial function.     

Plasma level changes of fibrinopeptide a after uncomplicated coronary angioplasty

Fibrinopeptide A (FPA) is a small polypeptide cleaved from fibrinogen by thrombin, has a short half-life, and is considered a sensitive biochemical marker of thrombin activity, fibrin generation, and ongoing thrombosis. Increased plasma levels of FPA have been reported in various procoagulable and thrombotic medical and cardiovascular disorders, including acute myocardial infarction, unstable angina, and sudden cardiac death. However, activation of thrombosis by the arterial injury incurred during coronary angioplasty has not been systematically examined with use of plasma FPA measurements. To detect and monitor activation of thrombosis by coronary angioplasty, plasma levels of FPA were obtained by venipuncture and measured by radioimmunoassay before, immediately after, 24 to 48 h later, and 1 and 3 months after uncomplicated coronary angioplasty. From December 1990 through June 1991, FPA was measured in 30 patients (28 men and 2 women, aged 54 ± 9 years) with coronary artery disease who were undergoing coronary angioplasty. The mean left ventricular ejection fraction was 55 ± 7%. The dilated vessel was the left anterior descending coronary artery in 20 patients (together with a second vessel in 2), the right coronary artery in 9, and the left circumflex in 1. The procedure was successful and free of major complications in all patients. Before angioplasty the FPA levels averaged 6.50 ± 1.18 ng/ml. Shortly after angioplasty they rose to 20.20 ± 7.91 ng/ml (p = 0.08) despite intravenous heparin. At 24 to 48 h and after heparin had been discontinued for at least 4 h, the mean FPA levels were significantly higher (32.33 ± 10.86 ng/ml) compared with baseline values (p = 0.025 ). At 1 month after the procedure, the FPA levels measured in 22 patients were lower but still elevated (20.25 ± 9.29 ng/ml), albeit nonsignificantly, compared with baseline values, and at 3 months they had fallen to baseline values (4.84 ± 2.20 ng/ml, n = 11). No patient developed restenosis during the study period of 1 to 3 months, during which all patients were receiving aspirin. We conclude that, as reflected by increased FPA levels, angioplasty, most likely due to arterial injury incurred, activates thrombin and generates ongoing coronary thrombosis, which is not suppressed by heparin or aspirin and appears to extend at least through the first month after the procedure.     

The relationship between fish consumption and the risk of developing acute coronary syndromes among smokers: the CARDIO2000 case-control study

BACKGROUND AND AIM: We sought to investigate the relationship between fish consumption and the risk of developing non-fatal acute coronary syndromes (ACS) among current smokers. METHODS AND RESULTS: During 2000-2001, we conducted the CARDIO2000 case-control study that included patients hospitalized for a first event of ACS and matched (age, sex) individuals without clinical evidence of CHD (controls), from all the Greek regions. In the present analysis we studied data from 519 men (59+/-10 years old) and 45 women (62+/-9 years old) patients, as well as 444 men and 90 women controls, matched for age with the patients that reported current smoking. To evaluate the hypothesis tested we applied conditional logistic regression analysis after controlling for several potential confounders. Overall, 94% of controls and patients reported fish consumption at least once a week. Compared to low fish consumption (<60 g/week), moderate (60-180 g/week) intake was associated with 15% (p<0.05) lower risk of ACS, while increased (180-300 g/week, or >300 g/week) consumption was associated with 18% (p<0.05) and 19% (p = 0.53) higher risk, respectively. CONCLUSION: Moderate fish consumption seems to moderate the deleterious effect of smoking on the occurrence of ACS. However, increased intake does not seem to confer any benefit on coronary risk.     

Acute combined effects of olive oil and wine on pressure wave reflections: another beneficial influence of the Mediterranean diet antioxidants?

OBJECTIVES: Combined consumption of olive oil and wine is common in the Mediterranean diet, but there are no data concerning their synergistic haemodynamic response. We sought to determine the combined postprandial effects of wine and olive oil on wave reflections and central haemodynamics. METHODS: Fifteen healthy subjects consumed four standard meals on different days, containing 50 g of olive oil and 250 ml of wine, in a randomized cross-over study design. Two types of wine [red (R) and white (W)] and two types of olive oil [green (G) and refined (O) (rich and poor in antioxidants, respectively)] were used in all possible combinations (RO, RG, WO and WG). Applanation tonometry and aortic pulse wave analysis were performed when fasting and 1, 2 and 3 h postprandially. A second group of 15 healthy individuals matched for age, gender and body mass index served as the control group. RESULTS: All meals decreased AIx (RO and RG, P < 0.001; WO, P = 0.007; and WG, P = 0.039). The AIx reduction after RG, RO, WO and WG was significantly different from the respective AIx response of the control group. No difference was observed in the reduction of AIx between sessions, but a significantly earlier peak decrease in AIx, as well as a more prolonged decreasing effect, was observed after RG and RO consumption compared to WO and WG. Central systolic and diastolic pressures were diminished after all four combinations of wine and olive oil (P < 0.05). CONCLUSIONS: Combined consumption of wine and olive oil provided beneficial postprandial effects on haemodynamics. These findings reveal an additional favourable effect of components of the Mediterranean diet on haemodynamics in the postprandial state.     

Apolipoprotein E genotype in dyslipidemic patients and response of blood lipids and inflammatory markers to alpha-linolenic Acid

The objective of this study was to determine the effect of alpha-linolenic acid (ALA) supplementation on blood lipids and inflammatory markers, in relation to apolipoprotein (apo) E genotype. The diets of 50 dyslipidemic male patients were supplemented with 15 mL of flaxseed oil per day for 12 weeks. Retrospectively, 3 apo E genotype variants were found (epsilon2/epsilon3, n=7; epsilon3/epsilon3, n=33; epsilon3/epsilon4, n=10). No significant differences were found among apo E genotypes in any variables at baseline. ALA supplementation produced a small but significant decrease in high-density lipoprotein cholesterol (from 1.12 to 1.08 mmol/L, 43 to 42 mg/dL; p=0.008) and apo A-I levels (from 1.28 to 1.24 g/L, p=0.036) in the epsilon3/epsilon3 homozygotes. In addition, ALA supplementation resulted in a significant decrease in the serum concentration of serum amyloid A (SAA) (p=0.014), C-reactive protein (CRP) (p=0.013), macrophage colony-stimulating factor (MCSF) (p<0.001), and interleukin (IL)-6 (p=0.028). Serum SAA and MCSF were also significantly decreased in the epsilon3/epsilon4 group (p=0.005 and p=0.017, respectively). In contrast, ALA produced no effects on any of the inflammatory markers in the epsilon2/epsilon3 group. ALA may have beneficial effects on inflammation in dyslipidemic carriers of the apo epsilon3/epsilon3 and epsilon3/epsilon4 genotypes, but not in carriers of the epsilon2 allele.     

HIV-1 subtypes in Yugoslavia

To gain insight concerning the genetic diversity of HIV-1 viruses associated with the HIV-1 epidemic in Yugoslavia, 45 specimens from HIV-1-infected individuals were classified into subtypes by sequence-based phylogenetic analysis of the polymerase (pol) region of the viral genome. Forty-one of 45 specimens (91.2%) were identified as pol subtype B, 2 of 45 as subtype C (4.4%), 1 of 45 as CRF01_AE (2.2%), and 1 as CRF02_AG recombinant (2.2%). Nucleotide divergence among subtype B sequences was 4.8%. Results of this study show that among HIV-1-infected patients in Yugoslavia subtype B predominates (91.5%), whereas non-B subtypes are present at a low percentage, mostly related to travel abroad.     

Acquired pure red-cell aplasia associated with an increase of T cells bearing receptors for the Fc of IgG

A case of steroid-resistant acquired pure red-cell aplasia associated with a relative and absolute increase of TG cells is described. Removal of T cells enhanced erythroid colony and burst formation in vitro, and it is suggested that TG cells may be implicated in the pathogenesis of this case of acquired pure red-cell aplasia.