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Biomedical subjects

Michael Blazing

Publications and source records attributed to Michael Blazing.

5 recordsLinked to original sources
PubMed2006

A tale of two trials: a comparison of the post-acute coronary syndrome lipid-lowering trials A to Z and PROVE IT-TIMI 22.

BACKGROUND: The Aggrastat to Zocor (A to Z) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) trials compared intensive and moderate statin therapy after acute coronary syndromes, with seemingly disparate results. We analyzed the design, implementation, and results of the two trials in an attempt to clarify the effects of early intensive statin therapy. METHODS AND RESULTS: Study design, end points, and definitions were compared. In each trial, comparisons were made between intensive and moderate arms for both trials' primary end points and death/myocardial infarction. Analyses were performed over various time points: at the end of the trials, < or =4 months, and >4 months. Subjects in A to Z had higher-risk demographics. More PROVE IT subjects were enrolled in the United States and underwent prerandomization revascularization. The low-density lipoprotein (LDL) difference was greater in A to Z than in PROVE IT early (< or =4 months) but less late. Significant C-reactive protein reduction was earlier in PROVE IT. With common end points, event rates were higher in A to Z, and early favorable separation of event curves was seen in PROVE IT but not in A to Z. Clinical end point rates and reductions were similar in both trials after 4 months. CONCLUSIONS: An early benefit was seen in PROVE IT but not in A to Z. Late-phase results were similar. Factors that may explain this disparity include the intensity of therapy in the early phase, timing, and magnitude of LDL and C-reactive protein lowering, differences in early revascularization, and the play of chance. Taken together, the results of these trials support a strategy of early intensive statin therapy coupled with revascularization when appropriate in patients after acute coronary syndrome.

Aged↗
PubMed2005

The incidence and functional consequences of RT-associated cardiac perfusion defects.

PURPOSE: Radiation therapy (RT) for left-sided breast cancer has been associated with cardiac dysfunction. We herein assess the temporal nature and volume dependence of RT-induced left ventricular perfusion defects and whether these perfusion defects are related to changes in cardiac wall motion or alterations in ejection fraction. METHODS: From 1998 to 2001, 114 patients were enrolled onto an IRB-approved prospective clinical study to assess changes in regional and global cardiac function after RT for left-sided breast cancer. Patients were imaged 30 to 60 minutes after injection of technetium 99m sestamibi or tetrofosmin. Post-RT perfusion scans were compared with the pre-RT studies to assess for RT-induced perfusion defects as well as functional changes in wall motion and ejection fraction. Two-tailed Fisher's exact test and the Cochran-Armitage test for linear trends were used for statistical analysis. RESULTS: The incidence of new perfusion defects 6, 12, 18, and 24 months after RT was 27%, 29%, 38%, and 42%, respectively. New defects occurred in approximately 10% to 20% and 50% to 60% of patients with less than 5%, and greater than 5%, of their left ventricle included within the RT fields, respectively (p = 0.33 to 0.00008). The rates of wall motion abnormalities in patients with and without perfusion defects were 12% to 40% versus 0% to 9%, respectively; p values were 0.007 to 0.16, depending on the post-RT interval. CONCLUSIONS: Radiation therapy causes volume-dependent perfusion defects in approximately 40% of patients within 2 years of RT. These perfusion defects are associated with corresponding wall-motion abnormalities. Additional study is necessary to better define the long-term functional consequences of RT-induced perfusion defects.

Adult↗
PubMed2005

Predicting radiotherapy-induced cardiac perfusion defects.

The purpose of this work is to compare the efficacy of mathematical models in predicting the occurrence of radiotherapy-induced left ventricular perfusion defects assessed using single-photon emission computed tomography (SPECT). The basis of this study is data from 73 left-sided breast/ chestwall patients treated with tangential photon fields. The mathematical models compared were three commonly used parametric models [Lyman normal tissue complication probability (LNTCP), relative serialty (RS), generalized equivalent uniform dose (gEUD)] and a nonparametric model (Linear discriminant analysis--LDA). Data used by the models were the left ventricular dose--volume histograms, or SPECT-based dose-function histograms, and the presence/absence of SPECT perfusion defects 6 months postradiation therapy (21 patients developed defects). For the parametric models, maximum likelihood estimation and F-tests were used to fit the model parameters. The nonparametric LDA model step-wise selected features (volumes/function above dose levels) using a method based on receiver operating characteristics (ROC) analysis to best separate the groups with and without defects. Optimistic (upper bound) and pessimistic (lower bound) estimates of each model's predictive capability were generated using ROC curves. A higher area under the ROC curve indicates a more accurate model (a model that is always accurate has area = 1). The areas under these curves for different models were used to statistically test for differences between them. Pessimistic estimates of areas under the ROC curve using dose-volume histogram/ dose-function histogram inputs, in order of increasing prediction accuracy, were LNTCP (0.79/0.75), RS (0.80/0.77), gEUD (0.81/0.78), and LDA (0.84/0.86). Only the LDA model benefited from SPECT-based regional functional information. In general, the LDA model was statistically superior to the parametric models. The LDA model selected as features the left ventricular volumes above approximately 23 Gy (V23), essentially volume in field, and 33 Gy (V33), as best separating the groups with and without defects. In conclusion, the nonparametric LDA model appears to be a more accurate predictor of radiotherapy-induced left ventricular perfusion defects than commonly used parametric models.

Dose-Response Relationship, Radiation↗