Five-year follow-up of angiographic disease progression after medicine, angioplasty, or surgery

Background: Progression of atherosclerosis in coronary artery disease is observed through consecutive angiograms. Prognosis of this progression in patients randomized to different treatments has not been established. This study compared progression of coronary artery disease in native coronary arteries in patients undergoing surgery, angioplasty, or medical treatment. Methods: Patients (611) with stable multivessel coronary artery disease and preserved ventricular function were randomly assigned to CABG, PCI, or medical treatment alone (MT). After 5-year follow-up, 392 patients (64%) underwent new angiography. Progression was considered a new stenosis of >= 50% in an arterial segment previously considered normal or an increased grade of previous stenosis > 20% in nontreated vessels. Results: Of the 392 patients, 136 underwent CABG, 146 PCI, and 110 MT. Baseline characteristics were similar among treatment groups, except for more smokers and statin users in the MT group, more hypertensives and lower LDL-cholesterol levels in the CABG group, and more angina in the PCI group at study entry. Analysis showed greater progression in at least one native vessel in PCI patients (84%) compared with CABG (57%) and MT (74%) patients (p < 0.001). LAD coronary territory had higher progression compared with LCX and RCA (P < 0.001). PCI treatment, hypertension, male sex, and previous MI were independent risk factors for progression. No statistical difference existed between coronary events and the development of progression. Conclusion: The angioplasty treatment conferred greater progression in native coronary arteries, especially in the left anterior descending territories and treated vessels. The progression was independently associated with hypertension, male sex, and previous myocardial infarction.

Hypotheses, rationale, design, and methods for prognostic evaluation in type 2 diabetic patients with angiographically normal coronary arteries. The MASS IV-DM Trial

Background: The MASS IV-DM Trial is a large project from a single institution, the Heart Institute (InCor), University of Sao Paulo Medical School, Brazil to study ventricular function and coronary arteries in patients with type 2 diabetes mellitus. Methods/Design: The study will enroll 600 patients with type 2 diabetes who have angiographically normal ventricular function and coronary arteries. The goal of the MASS IV-DM Trial is to achieve a long-term evaluation of the development of coronary atherosclerosis by using angiograms and coronary-artery calcium scan by electron-beam computed tomography at baseline and after 5 years of follow-up. In addition, the incidence of major cardiovascular events, the dysfunction of various organs involved in this disease, particularly microalbuminuria and renal function, will be analyzed through clinical evaluation. In addition, an effort will be made to investigate in depth the presence of major cardiovascular risk factors, especially the biochemical profile, metabolic syndrome inflammatory activity, oxidative stress, endothelial function, prothrombotic factors, and profibrinolytic and platelet activity. An evaluation will be made of the polymorphism as a determinant of disease and its possible role in the genesis of micro- and macrovascular damage. Discussion: The MASS IV-DM trial is designed to include diabetic patients with clinically suspected myocardial ischemia in whom conventional angiography shows angiographically normal coronary arteries. The result of extensive investigation including angiographic follow-up by several methods, vascular reactivity, pro-thrombotic mechanisms, genetic and biochemical studies may facilitate the understanding of so-called micro- and macrovascular disease of DM.

Acute and chronic effects of exercise on inflammatory markers and B-type natriuretic peptide in patients with coronary artery disease

Few studies have prospectively addressed the effects of exercise in the inflammatory activity of patients with coronary artery disease (CAD). We sought to evaluate the consequences of an acute bout of exercise on inflammatory markers and BNP in untrained CAD patients before and after randomization to a training program. 34 CAD patients underwent a 50-min acute exercise session on a cycle-ergometer at 65% peak oxygen uptake before and after blood sampling. They were then randomized to a 4-month chronic exercise program (15 patients) or general lifestyle recommendations (19 patients), undergoing a new acute session of exercise after that. In the overall population, acute exercise caused a significant increase in C-reactive protein [CRP; 1.79 (4.49) vs. 1.94 (4.89) mg/L, P < 0.001], monokine induced by interferon-gamma [Mig; 351 (324) vs. 373 (330) pg/mL, P = 0.027] and vascular adhesion molecule-1 [VCAM-1; 226 (82) vs. 252 (110) pg/mL, P = 0.02]. After 4-months, in exercise-trained patients, there was a significant decrease in the inflammatory response provoked by the acute exercise compared to patients in the control group reflected by a significant decrease in the differences between rest and post-exercise levels of CRP [-0.29 (0.84) mg/L vs. -0.11 (0.21) mg/L, P = 0.05]. Resting BNP was also significantly lower in exercise-trained patients when compared to untrained controls [15.6 (16.2) vs. 9.7 (11.4) pg/mL, P = 0.04 and 19.2 (27.8) vs. 23.2 (27.5) pg/mL, P = 0.76; respectively]. Chronic exercise training might partially reverse the inflammatory response caused by acute exercise in CAD patients. These results suggest that regular exercise is an important nonpharmacological strategy to the improvement in inflammation in CAD patients.

Quality of life after coronary artery bypass surgery

This study assessed the quality of life (QoL) of 124 people with coronary artery disease who had coronary artery bypass surgery in a hospital in Brazil, by using the Modified Flanagan`s QoL instrument as the outcome measure. In addition, we studied the association between QoL and demographic, clinical, and perceived health status (using SF-36 Health Survey) measures. The mean for the Modified Flanagan`s QoL was high (M = 84.8, SD = 13.6) when compared to similar studies in the United States. In a linear regression analysis, the SF-36 subscales of vitality, and general and mental health were statistically significant (p < .01 for all), after adjusting for other demographic and clinical variables. Increasing values of those SF-36 subscales corresponded to increasing Modified Flanagan`s QoL. Despite the limitations of the study, this result suggests that future clinical interventions aimed to improve QoL in this population could focus on the patient`s psychological conditions after the surgery.

Design of pressure vessels using shape optimization: An integrated approach

Previous papers related to the optimization of pressure vessels have considered the optimization of the nozzle independently from the dished end. This approach generates problems such as thickness variation from nozzle to dished end (coupling cylindrical region) and, as a consequence, it reduces the optimality of the final result which may also be influenced by the boundary conditions. Thus, this work discusses shape optimization of axisymmetric pressure vessels considering an integrated approach in which the entire pressure vessel model is used in conjunction with a multi-objective function that aims to minimize the von-Mises mechanical stress from nozzle to head. Representative examples are examined and solutions obtained for the entire vessel considering temperature and pressure loading. It is noteworthy that different shapes from the usual ones are obtained. Even though such different shapes may not be profitable considering present manufacturing processes, they may be competitive for future manufacturing technologies, and contribute to a better understanding of the actual influence of shape in the behavior of pressure vessels. (C) 2011 Elsevier Ltd. All rights reserved.

Estimating wave spectra from the motions of moored vessels: Experimental validation

The practicability of estimating directional wave spectra based on a vessel`s 1st order response has been recently addressed by several researchers. Different alternatives regarding statistical inference methods and possible drawbacks that could arise from their application have been extensively discussed, with an apparent preference for estimations based on Bayesian inference algorithms. Most of the results on this matter, however, rely exclusively on numerical simulations or at best on few and sparse full-scale measurements, comprising a questionable basis for validation purposes. This paper discusses several issues that have recently been debated regarding the advantages of Bayesian inference and different alternatives for its implementation. Among those are the definition of the best set of input motions, the number of parameters required for guaranteeing smoothness of the spectrum in frequency and direction and how to determine their optimum values. These subjects are addressed in the light of an extensive experimental campaign performed with a small-scale model of an FPSO platform (VLCC hull), which was conducted in an ocean basin in Brazil. Tests involved long and short crested seas with variable levels of directional spreading and also bimodal conditions. The calibration spectra measured in the tank by means of an array of wave probes configured the paradigm for estimations. Results showed that a wide range of sea conditions could be estimated with good precision, even those with somewhat low peak periods. Some possible drawbacks that have been pointed out in previous works concerning the viability of employing large vessels for such a task are then refuted. Also, it is shown that a second parameter for smoothing the spectrum in frequency may indeed increase the accuracy in some situations, although the criterion usually proposed for estimating the optimum values (ABIC) demands large computational effort and does not seem adequate for practical on-board systems, which require expeditious estimations. (C) 2009 Elsevier Ltd. All rights reserved.

AUTOMATIC CORONARY WALL SEGMENTATION IN INTRAVASCULAR ULTRASOUND IMAGES USING BINARY MORPHOLOGICAL RECONSTRUCTION

Intravascular ultrasound (IVUS) image segmentation can provide more detailed vessel and plaque information, resulting in better diagnostics, evaluation and therapy planning. A novel automatic segmentation proposal is described herein; the method relies on a binary morphological object reconstruction to segment the coronary wall in IVUS images. First, a preprocessing followed by a feature extraction block are performed, allowing for the desired information to be extracted. Afterward, binary versions of the desired objects are reconstructed, and their contours are extracted to segment the image. The effectiveness is demonstrated by segmenting 1300 images, in which the outcomes had a strong correlation to their corresponding gold standard. Moreover, the results were also corroborated statistically by having as high as 92.72% and 91.9% of true positive area fraction for the lumen and media adventitia border, respectively. In addition, this approach can be adapted easily and applied to other related modalities, such as intravascular optical coherence tomography and intravascular magnetic resonance imaging. (E-mail: matheuscardosomg@hotmail.com) (C) 2011 World Federation for Ultrasound in Medicine & Biology.

In Vitro Simultaneous Transfer of Lipids to HDL in Coronary Artery Disease and in Statin Treatment

The exchange of lipids with cells and other lipoproteins is a crucial process in HDL metabolism and for HDL antiatherogenic function. Here, we tested a practical method to quantify the simultaneous transfer to HDL of phospholipids, free-cholesterol, esterified cholesterol and triacylglycerols and to verify the lipid transfer in patients with coronary artery disease (CAD) or undergoing statin treatment. Twenty-eight control subjects without CAD, 27 with CAD and 25 CAD patients under simvastatin treatment were studied. Plasma samples were incubated with a donor nanoemulsion prepared by ultrasonication of the constituent lipids and labeled with radioactive lipids; % lipids transferred to HDL were quantified in the HDL-containing supernatant after chemical precipitation of non-HDL fractions and the nanoemulsion. The assay was precise and reproducible. Increase of temperature (4-37 A degrees C), of incubation period (5 min to 2 h), of HDL-cholesterol concentration (33-244 mg/dL) and of mass of nanoemulsion lipids (0.075-0.3 mg/mu L) resulted in increased lipid transfer from the nanoemulsion to HDL. In contrast, increasing pH (6.5-8.5) and albumin concentration (3.5-7.0 g/dL) did not affect lipid transfer. There was no difference between CAD and control non-CAD with regard to the lipid transfer, but statin treatment reduced the transfer to HDL of all four lipids. The test herein described is a valid and practical tool for exploring an important aspect of HDL metabolism.

Twelve-month Outcomes After Coronary Stenting With the Genous (TM) Bio-Engineered R Stent (TM) in Diabetic Patients from the e-HEALING Registry

Objectives: We compared 12-month outcomes, regarding ischemic events, repeat intervention, and ST, between diabetic and nondiabetic patients treated with the Genous (TM) EPC capturing R stent (TM) during routine nonurgent percutaneous coronary intervention (PCI) using data from the multicenter, prospective worldwide e-HEALING registry. Background: Diabetic patients have an increased risk for restenosis and stent thrombosis (ST). Methods: In the 4,996 patient e-HEALING registry, 273 were insulin requiring diabetics (IRD), 963 were non-IRD (NIRD), and 3,703 were nondiabetics. The 12-month primary outcome was target vessel failure (TVF), defined as target vessel-related cardiac death or myocardial infarction (MI) and target vessel revascularization. Secondary outcomes were the composite of cardiac death, MI or target lesion revascularization (TLR), and individual outcomes including ST. Cumulative event rates were estimated with the Kaplan-Meier method and compared with a log-rank test. Results: TVF rates were respectively 13.4% in IRD, 9.0% in NIRD, and 7.9% in nondiabetics (P < 0.01). This was mainly driven by a higher mortality hazard in IRD (P < 0.001) and NIRD (P = 0.07), compared with nondiabetics. TLR rates were comparable in NIRD and nondiabetics, but significantly higher in IRD (P = 0.04). No difference was observed in ST. Conclusion: The 1-year results of the Genous stent in a real-world population of diabetics show higher TVF rates in diabetics compared with nondiabetics, mainly driven by a higher mortality hazard. IRD is associated with a significant higher TLR hazard. Definite or probable ST in all diabetic patients was comparable with nondiabetics. (J Interven Cardiol 2011;24:285-294)

Coronary Calcification Is Associated With Lower Bone Formation Rate in CKD Patients Not Yet in Dialysis Treatment

Vascular calcification is a strong prognostic marker of mortality in hemodialysis patients and has been associated with bone metabolism disorders in this population. In earlier stages of chronic kidney disease (CKD), vascular calcification also has been documented. This study evaluated the association between coronary artery calcification (CAC) and bone histomorphometric parameters in CKD predialysis patients assessed by multislice coronary tomography and by undecalcified bone biopsy. CAC was detected in 33 (66%) patients, and their median calcium score was 89.7 (0.4-2299.3 AU). The most frequent bone histologic alterations observed included low trabecular bone volume, increased eroded and osteoclast surfaces, and low bone-formation rate (BFR/BS). Multiple logistic regression analysis, adjusted for age, sex, and diabetes, showed that BFR/BS was independently associated with the presence of coronary calcification [p=.009; odd ratio (OR) = 0.15; 95% confidence interval (Cl) 0.036-0.619] This study showed a high prevalence of CAC in asymptomatic predialysis CKD patients. Also, there was an independent association of low bone formation and CAC in this population. In conclusion, our results provide evidence that low bone-formation rate constitutes another nontraditional risk factor for cardiovascular disease in CKD patients. 2010 American Society for Bone and Mineral Research.

Randomized Evaluation of Two Drug-Eluting Stents With Identical Metallic Platform and Biodegradable Polymer But Different Agents (Paclitaxel or Sirolimus) Compared Against Bare Stents: 1-Year Results of the PAINT Trial

Objectives: We tested two novel drug-eluting stents (DES), covered with a biodegradable-polymer carrier and releasing paclitaxel or sirolimus, which were compared against a bare metal stent (primary objective). The DES differed by the drug, but were identical otherwise, allowing to compare the anti-restenosis effects of sirolimus versus paclitaxel (secondary objective). Background: The efficacy of novel DES with biodegradable polymers should be tested in the context of randomized trials, even when using drugs known to be effective, such as sirolimus and paclitaxel. Methods: Overall, 274 patients with de novo coronary lesions in native vessels scheduled for stent implantation were randomly assigned (2:21 ratio) for the paclitaxel (n = 111), sirolimus (n = 106), or bare metal stent (n = 57) groups. Angiographic follow-up was obtained at 9 months and major cardiac adverse events up to 12 months. Results: Both paclitaxel and sirolimus stents reduced the 9-month in-stent late loss (0.54-0.44 mm, 0.32-0.43 mm, vs. 0.90-0.45 mm respectively), and 1-year risk of target vessel revascularization and combined major adverse cardiac events (P < 0.05 for both, in all comparisons), compared with controls. Sirolimus stents had lower late loss than paclitaxel stents (P < 0.01), but similar 1-year clinical outcomes. There were no differences in the risk of death, infarction, or stent thrombosis among the study groups. Conclusion: Both novel DES were effective in reducing neointimal hyperplasia and 1-year re-intervention, compared to bare metal stents. Our findings also suggest that sirolimus is more effective than paclitaxel in reducing angiographic neointima, although this effect was not associated with better clinical outcomes. (C) 2009 Wiley-Liss, Inc.

Is Coronary Artery Calcification Associated with Vertebral Bone Density in Nondialyzed Chronic Kidney Disease Patients?

Background and objectives Low bone mineral density and coronary artery calcification (CAC) are highly prevalent among chronic kidney disease (CKD) patients, and both conditions are strongly associated with higher mortality. The study presented here aimed to investigate whether reduced vertebral bone density (VBD) was associated with the presence of CAC in the earlier stages of CKD. Design, setting, participants, & measurements Seventy-two nondialyzed CKD patients (age 52 +/- 11.7 years, 70% male, 42% diabetics, creatinine clearance 40.4 +/- 18.2 ml/min per 1.73 m(2)) were studied. VBD and CAC were quantified by computed tomography. Results CAC > 10 Agatston units (AU) was observed in 50% of the patients (median 120 AU [interquartile range 32 to 584 AU]), and a calcification score >= 400 AU was found in 19% (736 [527 to 1012] AU). VBD (190 +/- 52 Hounsfield units) correlated inversely with age (r = -0.41, P < 0.001) and calcium score (r = -0.31, P = 0.01), and no correlation was found with gender, creatinine clearance, proteinuria, lipid profile, mineral parameters, body mass index, and diabetes. Patients in the lowest tertile of VBD had expressively increased calcium score in comparison to the middle and highest tertile groups. In the multiple logistic regression analysis adjusting for confounding variables, low VBD was independently associated with the presence of CAC. Conclusions Low VBD was associated with CAC in nondialyzed CKD patients. The authors suggest that low VBD might constitute another nontraditional risk factor for cardiovascular disease in CKD. Clin J Am Soc Nephrol 6: 1456-1462, 2011. doi: 10.2215/CJN.10061110

Association of Changes in Bone Remodeling and Coronary Calcification in Hemodialysis Patients: A Prospective Study

Background: Vascular calcification is common and constitutes a prognostic marker of mortality in the hemodialysis population. Derangements of mineral metabolism may influence its development. The aim of this study is to prospectively evaluate the association between bone remodeling disorders and progression of coronary artery calcification (CAC) in hemodialysis patients. Study Design: Cohort study nested within a randomized controlled trial. Setting & Participants: 64 stable hemodialysis patients. Predictor: Bone-related laboratory parameters and bone histomorphometric characteristics at baseline and after 1 year of follow-up. Outcomes: Progression of CAC assessed by means of coronary multislice tomography at baseline and after 1 year of follow-up. Baseline calcification score of 30 Agatston units or greater was defined as calcification. Change in calcification score of 15% or greater was defined as progression. Results: Of 64 patients, 26 (40%) had CAC at baseline and 38 (60%) did not. Participants without CAC at baseline were younger (P < 0.001), mainly men (P = 0.03) and nonwhite (P = 0.003), and had lower serum osteoprotegerin levels (P = 0.003) and higher trabecular bone volume (P = 0.001). Age (P 0.003; beta coefficient = 1.107; 95% confidence interval [Cl], 1.036 to 1.183) and trabecular bone volume (P = 0.006; beta coefficient = 0.828; 95% Cl, 0.723 to 0.948) were predictors for CAC development. Of 38 participants who had calcification at baseline, 26 (68%) had CAC progression in 1 year. Progressors had lower bone-specific alkaline phosphatase (P = 0.03) and deoxypyridinoline levels (P = 0.02) on follow-up, and low turnover was mainly diagnosed at the 12-month bone biopsy (P = 0.04). Low-turnover bone status at the 12-month bone biopsy was the only independent predictor for CAC progression (P = 0.04; beta coefficient = 4.5; 95% Cl, 1.04 to 19.39). According to bone histological examination, nonprogressors with initially high turnover (n = 5) subsequently had decreased bone formation rate (P = 0.03), and those initially with low turnover (n = 7) subsequently had increased bone formation rate (P = 0.003) and osteoid volume (P = 0.001). Limitations: Relatively small population, absence of patients with severe hyperparathyroidism, short observational period. Conclusions: Lower trabecular bone volume was associated with CAC development, whereas improvement in bone turnover was associated with lower CAC progression in patients with high- and low-turnover bone disorders. Because CAC is implicated in cardiovascular mortality, bone derangements may constitute a modifiable mortality risk factor in hemodialysis patients.

Prognostic Value of Dobutamine Stress Echocardiography With Early Injection of Atropine With Versus Without Chronic Beta-Blocker Therapy in Patients With Known or Suspected Coronary Heart Disease

Although a new protocol of dobutamine stress echocardiography with the early injection of atropine (EA-DSE) has been demonstrated to be useful in reducing adverse effects and increasing the number of effective tests and to have similar accuracy for detecting coronary artery disease (CAD) compared with conventional protocols, no data exist regarding its ability to predict long-term events. The aim of this study was to determine the prognostic value of EA-DSE and the effects of the long-term use of beta blockers on it. A retrospective evaluation of 844 patients who underwent EA-DSE for known or suspected CAD was performed; 309 (37%) were receiving beta blockers. During a median follow-up period of 24 months, 102 events (12%) occurred. On univariate analysis, predictors of events were the ejection fraction (p <0.001), male gender (p <0.001), previous myocardial infarction (p <0.001), angiotensin-converting enzyme inhibitor therapy (p = 0.021), calcium channel blocker therapy (p = 0.034), and abnormal results on EA-DSE (p <0.001). On multivariate analysis, the independent predictors of events were male gender (relative risk [RR] 1.78, 95% confidence interval [CI] 1.13 to 2.81, p = 0.013) and abnormal results on EA-DSE (RR 4.45, 95% CI 2.84 to 7.01, p <0.0001). Normal results on EA-DSE with P blockers were associated with a nonsignificant higher incidence of events than normal results on EA-DSE without beta blockers (RR 1.29, 95% CI 0.58 to 2.87, p = 0.54). Abnormal results on EA-DSE with beta blockers had an RR of 4.97 (95% CI 2.79 to 8.87, p <0.001) compared with normal results, while abnormal results on EA-DSE without beta blockers had an RR of 5.96 (95% CI 3.41 to 10.44, p <0.001) for events, with no difference between groups (p = 0.36). In conclusion, the detection of fixed or inducible wall motion abnormalities during EA-DSE was an independent predictor of long-term events in patients with known or suspected CAD. The prognostic value of EA-DSE was not affected by the long-term use of beta blockers. (C) 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1291-1295)

Usefulness of Proteinuria as a Prognostic Marker of Mortality and Cardiovascular Events Among Patients Undergoing Percutaneous Coronary Intervention (Data from the Evaluation of Oral Xemilofiban in Controlling Thrombotic Events [EXCITE] Trial)

Proteinuria was associated with cardiovascular events and mortality in community-based cohorts. The association of proteinuria with mortality and cardiovascular events in patients undergoing percutaneous coronary intervention (PCI) was unknown. The association of urinary dipstick proteinuria with mortality and cardiovascular events (composite of death, myocardial infarction, or nonhemorrhagic stroke) in 5,835 subjects of the EXCITE trial was evaluated. Dipstick urinalysis was performed before PCI, and proteinuria was defined as trace or greater. Subjects were followed up for 210 days/7 months after enrollment for the occurrence of events. Multivariate Cox regression analysis evaluated the independent association of proteinuria with each outcome. Mean age was 59 years, 21% were women, 18% had diabetes mellitus, and mean estimated glomerular filtration rate was 90 ml/min/1.73 m(2). Proteinuria was present in 750 patients (13%). During follow-up, 22 subjects (2.9%) with proteinuria and 54 subjects (1.1%) without proteinuria died (adjusted hazard ratio 2.83, 95% confidence interval [CI] 1.65 to 4.84, p <0.001). The severity of proteinuria attenuated the strength of the association with mortality after PCI (low-grade proteinuria, hazard ratio 2.67, 95% CI 1.50 to 4.75; high-grade proteinuria, hazard ratio 3.76, 95% CI 1.24 to 11.37). No significant association was present for cardiovascular events during the relatively short follow-up, but high-grade proteinuria tended toward increased risk of cardiovascular events (hazard ratio 1.45, 95% CI 0.81 to 2.61). In conclusion, proteinuria was strongly and independently associated with mortality in patients undergoing PCI. These data suggest that such a relatively simple and clinically easy to use tool as urinary dipstick may be useful to identify and treat patients at high risk of mortality at the time of PCI. (C) 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1151-1155)