Medical Student Research Fellowship for Summer 2006

Mentor: Manisha Shah
Department: Internal Medicine - Cardiology
Room number:HA9.122
Mail Code: 9047
Phone number: 214-645-7500; 214-896-2782
E-mail: Manisha.shah@utsouthwestern.edu
Project title: The relationship of abnormal aortic compliance with diastolic dysfunction.

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable):

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) PATIENT BASED

Brief Description of Project:
Goals of project for medical student:
1. Understand cardiovascular physiology in regard to aortic compliance and diastolic function.
2. Understand MRI technology and clinical applications.
3. MRI data analysis of diastolic function and aortic compliance.
4. Study data analysis and data presentation.

This study aims to examine the relationship between aortic compliance and diastolic function in the Dallas Heart Study cohort. A positive relationship between abnormal aortic compliance and diastolic dysfunction would indicate that a similar pathologic process is occurring in both the vascular tissue and the cardiac tissue.

Study population: Subgroup chosen from the Dallas Heart Prevention Study cohort according to aortic compliance measurements.
Design: The study group will be those with abnormal aortic compliance. The control group will be age-matched subjects with normal aortic compliance.
Blood pressure status will be considered in the statistical analysis as a potential effect modifier.
Abnormal Aortic Compliance (distensability): To be determined by choosing individuals who have reduced aortic compliance values that are 2 standard deviations from the study population mean.

Exclusion Criteria: Left ventricular systolic function < 40%

Sample Size Analysis: We expect at least a 20%difference in diastolic function (peak filling rate) between normal and abnormal aortic compliance patients. Testing of the null hypothesis was with a significance level of .05 with a 95% chance of detecting a sample mean difference of .8 (20% difference) between each group. . Based on these expectations, the study will require 50 cases and 12 controls.

Evaluation: Magnetic resonance images obtained for the Reynolds database will be utilized.
1. Aortic Compliance: Using the Medis software, compliance is calculated as the change in volume over the change in change in pressure. Volume change is based on the difference of the maximum and minimum aortic area multiplied by a slice thickness of 8mm. The aorta area is measured at the level of the pulmonary artery bifurcation. The change in blood pressure is the pulse pressure determined by intra-MRI syphgnamometer measurements of blood pressure.
2. Diastolic function: Diastolic function will be based on the peak filling rate of the left ventricle during the diastolic phase. Reynolds MRI short-axis sequences will be used with a 6mm slice thickness and 4mm gap in between slices. Medis software is used to obtain end-diastolic contours of the endocardial border at each slice through the left ventricle. These contours will be modified manually for optimum edge-detection. The volume of each slice will be added to obtain the total volume of the left ventricle at a particular time in the cardiac cycle. The derivative of the volume-time curve will be the peak filling rate.
3. LV Mass, Ejection fraction, and LV Volume curve: Reynolds MRI short-axis sequences will be used with a 6mm slice thickness and 4mm gap. Medis software will allow automated contour placement around the epicardial and endocardial borders for all slices throughout the cardiac cycle. The contours will be modified manually for optimum edge-detection. LV mass will be the difference in endocardial and epicardial areas multiplied by 6mm, allowing for addition of all slices at the end-diastolic phase. Left ventricular volume is the addition of endocardial area for each slice times 6mm at end-diastole. Ejection fraction is the difference in volume between end-diastole and end-systole divided by the end-diastolic volume.

Analysis:
1. Univariate - distribution of peak filling rates (diastole)
2. Bivariate- Correlation between aortic compliance and diastolic flow pattern
Analysis of covariance adjusting for age and gender
3. Linear regression for assessing the relationship between aortic compliance and peak filling rate.
4. All p-values based on two-sided comparisons and p - value < 0.05 considered significant.
5. Multiple regression to determine predictors of diastolic function in subjects with and without normal aortic compliance. Hypertension and LV mass will be assessed as potential effect modifiers of diastolic function.

Previous Research Activities or Publications with Medical Students:
None previously with medical students.
Clinical projects with residents and fellows.

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