Prequtaneous transluminal angioplasty in patients with multivessel coronary disease: How important is complete revascularization for cardiac event-free survival?

AbstractThe relative influences of revascularizationstaus and baseline characteristics on long-term outcome were examined in 867 patients with multivessel coronarydisease who had undergone successful coronary angioplasty. These patients represented 83% of a total of 1,039 patients in whom angioplasty had been attempted with an in-hospltal mortality and infarction rate of 2.5% and 48%, respectively. Emergency coronary bypass surgery was needed in 4.9%. Of the 867 patients, 41% (group 1) were considered to have complete revascularization and 59% (group 2) to have incomplete revascularization. Univariate analysis revealed major differences between these two groups with patients in group 2 characterized by advanced age, more severe angina, a greater likelihood of previous coronary surgery and infarction, more extensive disease and poorer left ventricular function.Over a mean follow-up period of 26 months, the probability of event-free survival was significantly lower for group 2 only with respect to the need for coronary artery surgery (p = 0.004) and occurrence of severe angina (p = 0.04). The difference in modality was of borderline significance (p = 0.051) and there were no signiicant difference between 1 and 2 in either the incidence of myocardial infarction or the need for repeat angioplasty.Muitivariate analysis identified independent baseline predictors of late cardiac events that were then used to adjust the probabilities of event-free survival. This adjustment effectively removed any significant influence of completeness of revascuiarization on event-free survival for any of the above end points including the combination of death, myocardial infarction and need for coronary artery surgery. Therefore, late outcome in these patients is not significantly influenced by revascularization status but depends more on baseline patient characteristics

Spatial normalization improves the quality of genotype calling for Affymetrix SNP 6.0 arrays

<p>Abstract</p> <p>Background</p> <p>Microarray measurements are susceptible to a variety of experimental artifacts, some of which give rise to systematic biases that are spatially dependent in a unique way on each chip. It is likely that such artifacts affect many SNP arrays, but the normalization methods used in currently available genotyping algorithms make no attempt at spatial bias correction. Here, we propose an effective single-chip spatial bias removal procedure for Affymetrix 6.0 SNP arrays or platforms with similar design features. This procedure deals with both extreme and subtle biases and is intended to be applied before standard genotype calling algorithms.</p> <p>Results</p> <p>Application of the spatial bias adjustments on HapMap samples resulted in higher genotype call rates with equal or even better accuracy for thousands of SNPs. Consequently the normalization procedure is expected to lead to more meaningful biological inferences and could be valuable for genome-wide SNP analysis.</p> <p>Conclusions</p> <p>Spatial normalization can potentially rescue thousands of SNPs in a genetic study at the small cost of computational time. The approach is implemented in R and available from the authors upon request.</p

Determinants of Pulmonary Hypertension in Left Ventricular Dysfunction

AbstractObjectives. This study sought to analyze the determinants of pulmonary hypertension in patients with left ventricular dysfunction.Background. Pulmonary hypertension in patients with left ventricular dysfunction is a predictor of poor outcome. The independent role of cardiac functional abnormalities in the genesis of pulmonary hypertension is unclear.Methods. In 102 consecutive patients with primary left ventricular dysfunction (ejection fraction <50%), systolic pulmonary artery pressure was prospectively measured by Doppler echocardiography (using tricuspid regurgitant velocity), and left ventricular systolic and diastolic function, functional mitral regurgitation, cardiac output and left atrial volume were quantified.Results. Systolic pulmonary artery pressure was elevated in patients with left ventricular dysfunction (51 ± 14 mm Hg [mean ± SD]), but the range was wide (23 to 87 mm Hg). Of the numerous variables correlating significantly with systolic pulmonary artery pressure, the strongest were mitral deceleration time (r = −0.61, p = 0.0001; odds ratio of pulmonary pressure ≥50 mm Hg [95% confidence interval] if <150 ms, 48.8 [14.8 to 161]) and mitral effective regurgitant orifice (r = 0.50, p = 0.0001; odds ratio [95% confidence interval] if ≥20 mm2, 5.9 [2.3 to 15.5]). In multivariate analysis, these two variables were the strongest predictors of systolic pulmonary artery pressure in association with age (p = 0.005). Ejection fraction or end-systolic volume was not an independent predictor of pulmonary artery pressure.Conclusions. Pulmonary hypertension is frequent and highly variable in patients with left ventricular dysfunction. It is not independently related to the degree of left ventricular systolic dysfunction but is strongly associated with diastolic dysfunction (shorter mitral deceleration time) and the degree of functional mitral regurgitation (larger effective regurgitant orifice). These results emphasize the importance of assessing diastolic function and quantifying mitral regurgitation in patients with left ventricular dysfunction.(J Am Coll Cardiol 1997;29:153–9)

Amplitude-weighted mean velocity: Clinical utilization for quantitation of mitral regurgitation

AbstractObjectives. The purpose of this study was to determine the clinical usefulness of the amplitude-weighted mean velocity method for quantitation of mitral regurgitation.Background. Amplitude-weighted mean velocity is a nonvolumetric method for calculating the mitral regurgitant fraction. Its previous validation at one center mandated an independent assessment of its usefulness and limitations.Methods. In 56 patients with and 16 patients without mitral regugitation, the regurgitant fraction was measured simultaneously by amplitude-weighted mean velocity, quantitative Doppler study and quantitative two-dimensional echocardiography. In 16 patients, multiple gain settings were used to determine the influence of this variable on amplitude-weighted mean velocity.Results. In ptients without regurgitation, amplitude-weighted mean velocity showed more scattering of regurgitant fraction (−18% to 23%) than Doppler (p = 0.016) or two-dimensional echocardiography (p = 0.022). The absolute value of regurgitant fraction was (mean ± SD) 8 ± 6%, 4 ± 2% and 4 ± 3%, respectively (p = NS). With increasing gain, the amplitudeweighted mean velocity mitral and aortic integrals increased, but the calculated regurgitant fraction remained unchanged. In patients with mitral regurgitation, significant correlation was found between amplitude-weighted mean velocity and Doppler study (r = 0.79, p = 0.0001) and between implitude-weighted mean velocity and two-dimensional echocardiography (r = 0.76, p = 0.0001) for calculated regurgitant fraction, but the standard error of the estimate (12%) was large.Conclusions. The amplitude-weighted mean velocitycalculated regurgitant fraction is gain independent, whereas the aortic and mitral integrals are gain dependent. Compared with Doppler and two-dimensional echocardiography, It shows more scattering of values in patients without regurgitation, but the methods correlate significantly in patients with mitral regurgitation. Amplitude-weighted mean velocity can be used as a simple adjunctive tool for comprehensive, noninvasive quantitation of mitral regurgitation

Referral for coronary artery revascularization procedures after diagnostic coronary angiography: Evidence for gender bias?

AbstractObjectives. We sought to determine whether there is a gender bias in the selection of patients for coronary revascularization once the severity of the underlying coronary artery disease has been established with angiography.Background. It has been suggested that women with coronary artery disease are less likely to be referred for coronary angiography and coronary artery bypass surgery than men. Whether such a referral bias for revascularization procedures, including coronary angioplasty, is present once angiography has been performed is not clear.Methods. We retrospectively analyzed 22,795 patients with suspected coronary artery disease who underwent coronary angiography between 1981 and 1991 and compared the numbers of women and men who underwent either coronary artery bypass surgery or coronary angioplasty within 30 days of coronary angiography.Results. Angiography revealed significant (one-vessel or more) disease in 15,455 patients (52% of women, 76% of men). Despite worse symptoms, women had less extensive coronary disease than men as judged by the number of vessels diseased. Women were also more likely to have other co-morbid diseases. An equal proportion of women (54%) and men underwent revascularization procedures. After adjustment for baseline differences and age, differences in the two individual revascularization strategies were very small: More women tended to have coronary angioplasty ([absolute difference ± 1 SD] + 3.3 ± 0.7%, p < 0.0001), but fewer had coronary artery bypass surgery than men (−2.5 ± 0.8%, p = 0.003). When the two revascularization strategies were considered together, there was no significant gender difference in overall adjusted use of revascularization (+0.8 ± 0.9%, p = 0.41).Conclusions. Once diagnostic coronary angiography had been performed, no major differences in the overall utilization of revascularization procedures were noted for women compared with men

Exercise echocardiographic findings and outcome of patients referred for evaluation of dyspnea

AbstractObjectivesThe purpose of this study was to characterize the outcome of patients referred for exercise echocardiographic evaluation of dyspnea.BackgroundLittle information exists regarding outcome of patients with dyspnea.MethodsWe identified 443 patients with unexplained dyspnea, 2,033 with chest pain, and 587 with both symptoms referred for exercise echocardiography.ResultsCompared to those with chest pain alone, patients referred for dyspnea alone were older, predominately men, and had lower workload, lower ejection fraction (EF), more prior myocardial infarction (MI), and abnormal rest electrocardiograms. Patients with both symptoms were similar to those with dyspnea, but more had prior revascularization. Exercise echocardiography showed ischemia in 42% of patients with dyspnea, 19% with chest pain, and 58% with both symptoms. During 3.1 ± 1.8 years follow-up, cardiac death (5.2% vs. 0.9%, p < 0.0001) and nonfatal MI (4.7% vs. 2.0%, p < 0.0001) occurred more often in patients with dyspnea. Events in patients with both symptoms were similar to those with dyspnea, except for revascularization (20% vs. 13%, p = 0.0004). For patients with dyspnea, independent predictors of events were previous MI (hazard ratio [HR] 3.35, p < 0.0001), male gender (HR 1.94, p = 0.0252), EF (HR 0.95/10% increment, p < 0.0001), and increase in wall motion score index with exercise (HR 4.19/0.25 U, p < 0.0001), but not chest pain.ConclusionsPatients with unexplained dyspnea have a high likelihood of ischemia and an increased incidence of cardiac events. Exercise echocardiography provides independent information for identifying patients at risk. In patients with known or suspected coronary artery disease, dyspnea is a symptom requiring investigation

Coronary embolization after balloon angioplasty or thromolytic therapy: An autopsy study of 32 cases

AbstractObjectives. This study was undertaken to examine the nature, extent and clinical relevance of coronary embolism after balloon angioplasty or thrombolytic therapy, or both.Background. Histopathologic documentation of postinterventional coronary embolization has been reported in only 10 patients from five studies.Methods. This retrospective autopsy-based study included 32 patients, treated with balloon angioplasty or thrombolysis, or both, who died within 3 weeks of the procedure and underwent autopsy at the Mayo Clinic. Clinical variables included patient age and gender, artery treated, site and type of obstruction, type of intervention, success of the procedure, and postprocedural changes in the electrocardiogram (ECG), cardiac enzymes and hemodynamic status. Histopathologic variables included characteristics of treated plaques, acutely infarcted myocardium and coronary microemboli. Associations between microemboli and clinical and microscopic factors were evaluated by ttests and simple and multiple linear regression.Results. Emboli were observed in 26 (81%) of the 32 patients. Among 83 emboli, 95% were thrombotic or atheromatous. The presence of microemboli was associated statistically with the development of postprocedural infarct extension, new myocardial infarction or new ECG abnormalities. Moreover, the greatest number of microemboli were associated with intervention in the left anterior descending coronary artery, multiple interventional sites, postprocedural medial dissection and plaque rupture or extrusion.Conclusions. Among patients undergoing balloon angioplasty or thrombolytic therapy who die and undergo autopsy, coronary microemboli occur in a substantial percent. The frequency in survivors is unknown. However, in living patients who develop acute myocardial ischemia or new ECG abnormalities after these interventions, coronary microembolization should be considered a potential cause

GLOSSI: a method to assess the association of genetic loci-sets with complex diseases

<p>Abstract</p> <p>Background</p> <p>The developments of high-throughput genotyping technologies, which enable the simultaneous genotyping of hundreds of thousands of single nucleotide polymorphisms (SNP) have the potential to increase the benefits of genetic epidemiology studies. Although the enhanced resolution of these platforms increases the chance of interrogating functional SNPs that are themselves causative or in linkage disequilibrium with causal SNPs, commonly used single SNP-association approaches suffer from serious multiple hypothesis testing problems and provide limited insights into combinations of loci that may contribute to complex diseases. Drawing inspiration from Gene Set Enrichment Analysis developed for gene expression data, we have developed a method, named GLOSSI (Gene-loci Set Analysis), that integrates prior biological knowledge into the statistical analysis of genotyping data to test the association of a group of SNPs (loci-set) with complex disease phenotypes. The most significant loci-sets can be used to formulate hypotheses from a functional viewpoint that can be validated experimentally.</p> <p>Results</p> <p>In a simulation study, GLOSSI showed sufficient power to detect loci-sets with less than 10% of SNPs having moderate-to-large effect sizes and intermediate minor allele frequency values. When applied to a biological dataset where no single SNP-association was found in a previous study, GLOSSI was able to identify several loci-sets that are significantly related to blood pressure response to an antihypertensive drug.</p> <p>Conclusion</p> <p>GLOSSI is valuable for association of SNPs at multiple genetic loci with complex disease phenotypes. In contrast to methods based on the Kolmogorov-Smirnov statistic, the approach is parametric and only utilizes information from within the interrogated loci-set. It properly accounts for dependency among SNPs and allows the testing of loci-sets of any size.</p

Effect of external beam irradiation on neointimal hyperplasia after experimental coronary artery injury

AbstractHuman coronary artery restenosis after percutaneous revascularization is a response to mechanical injury. Smooth muscle cell proliferation is a major component of restenosis, resulting in obstructive neointimal hyperplasia. Because ionizing radiation inhibits cellular proliferation, this study tested in a porcine coronary injury model the hypothesis that the hyperplastic response to coronary artery injury would be attenuated by X-irradiation.Deep arterial injury was produced in 37 porcine left anterior descending coronary artery segments with overexpanded, percutaneously delivered tantalum wire coils. Three groups of pigs were irradiated with 300-kV X-rays after coil injury: Group I (n = 10), 400 cGy at 1 day; Group II (n = 10), 400 cGy at 1 day and 400 cGy at 4 days and Group III (n = 9), 800 cGy at 1 day. Eight pigs in the control group underwent identical injury but received no radiation. Treatment efficacy was histologically assessed by measuring neointimal thickness and percent area stenosis.Mean neointimal thickness in all irradiated groups was significantly higher than in the control groups and thickness was proportional to X-ray dose.X-irradiation delivered at these doses and times did not inhibit proliferative neointima. Rather, it accentuated the neointimal response to acute arterial injury and may have potentiated that injury

Use of echocardiography in the management of congestive heart failure in the community

AbstractObjectives. We evaluated the use and the impact of echocardiography in patients receiving an initial diagnosis of congestive heart failure in Olmsted County, Minnesota, in 1991.Background. The American College of Cardiology/American Heart Association clinical practice guidelines recommend echocardiography in all patients with suspected congestive heart failure. No data are available on use and impact of echocardiography in management of congestive heart failure in a community.Methods. The medical records linkage system of the Rochester Epidemiology Project was used to identify all 216 patients who satisfied the Framingham criteria for congestive heart failure. Of these, 137 (63%) underwent echocardiography within 3 weeks before or after the episode of congestive heart failure (Echo group), and the other 79 patients constitute the No-Echo group.Results. The No-Echo group patients were older (p = 0.022), were more likely to be female (p = 0.072), had milder symptoms (p = 0.001) and were less often hospitalized at diagnosis (p = 0.001). Fewer patients in the No-Echo group were treated with angiotensin-converting enzyme inhibitors (p = 0.001). Advanced age (≥80 years), lower New York Heart Association functional class, absence of a fourth heart sound on examination, absence of cardiomegaly or signs of congestive heart failure on chest radiography and absence of known valve disease were independently related to the decision not to obtain an echocardiogram. Survival after adjustment for age, functional class and gender was lower in the No-Echo group than the Echo group (risk ratio = 0.607, p = 0.017).Conclusions. The underuse of echocardiography appears to be associated with poorer survival and underuse of angiotensin-converting enzyme inhibitor therapy