The transmural extent of scar (TME) can now be measured with contrast-enhanced magnetic resonance imaging. The impact of TME on myocardial function including contractile function at rest and with stress (dobutamine echo), perfusion (thallium SPECT) and synthetic function (brain natriuretic peptide) has not been closely examined. This is the major subject of this thesis.
Assessment of myocardial viability by dobutamine stress echo (DbE) and resting regional LV dysfunction (a prerequisite for viability) by two-dimensional echo (2DE) rely on visual assessment of left ventricular wall motion. However, the subjectivity of visual assessment has been criticized 1-5. In order to study the effect of TME on left ventricular contractile function both in the resting state and during DbE it was first important for us to assess the validity of visual wall motion scoring. The excellent spatial resolution of cardiac MRI allows accurate measurement of end systolic wall thickness (ESWT), end diastolic wall thickness (EDWT), absolute wall thickening (AT) and percentage thickening (%T) which are some of the determinants of visually assessed wall motion scoring on 2DE, as well as on cardiac magnetic resonance imaging (MRI).
The first study presented compares these MRI measured thickening parameters with visual wall motion scoring (WMS) with the aim of demonstrating objectivity in visual wall motion scoring, thereby affirming its validity. We studied 536 segments from 59 patients with ischemic LV dysfunction after myocardial infarction. Cardiac MRI and 2DE images were obtained. LV ejection fraction (LVEF) was 40±10% by 2DE and 43±11% by MRI. Visual WMS by 2DE and MRI showed moderate agreement (Kappa = 0.44). An AT < 3.0 mm had a sensitivity of 69% and a specificity of 69% for predicting segments with abnormal WMS by MRI and an AT < 2.5 mm had a sensitivity of 70% and a specificity of 67% for predicting segments with abnormal WMS by 2DE. A WMS of 1 (i.e. normal resting wall motion) had sensitivities of 62% and 60% by MRI and 2DE respectively and specificity of 70% by either MRI or 2DE for predicting %T of > or = 50. It was concluded that visually assessed WMS by 2DE and MRI are similar, and visual assessment by MRI correlates significantly with objective thickening measurements.
Left ventricular dysfunction in patients with ischemic cardiomyopathy causes significant morbidity and mortality. This enormous problem may be at least partly solved by the revascularization of viable myocardium (defined as myocardium with reduced contractile function that will recover this function-usually after being revascularized 6.7). This requires the accurate, convenient and cost-effective identification of myocardial viability. DbE and Thallium SPECT (Tl SPECT) are the most common means of identifying viable myocardium and are likely to remain so. Yet DbE and Tl SPECT may give discordant results. The discrepancies between the two are often attributed to differences between contractile reserve and membrane integrity, but may also reflect a disproportionate influence of nontransmural scar on thickening at DbE. Contrast-enhanced MRI (ceMRI) has enabled measurement of TME.
In the second study we sought to determine whether the TME explains discordances between DbE and Tl-SPECT in the detection of viable myocardium (VM). Sixty patients with post infarction left ventricular dysfunction underwent standard rest-late redistribution Tl-SPECT and DbE. Contrast-enhanced magnetic resonance imaging (ceMRI) was used to divide TME into five groups: 0%, <25%, 26% to 50%, 51% to75%, and >75% of the wall thickness replaced by scar. As TME increased, both the mean Tl uptake and change in wall motion score decreased significantly (both p < 0.001). However, the presence of subendocardial scar was insufficient to prevent thickening; >50% of segments still showed contractile function with TME of 25% to 75%, although residual function was uncommon with TME >75%. The relationship of both tests to increasing TME was similar, but Tl SPECT identified VM more frequently than DbE in all groups. Among segments without scar or with small amounts of scar (<25% TME), >50% were viable by Tl SPECT. We concluded the following. The likelihood of residual resting contractile function decreases with increasing TME, but residual function is seen in many segments with >25% TME. The reduction of contractile reserve and thallium activity is comparable with increasing TME. TME is a major determinant of discordance between the DbE and Tl SPECT, but discordance is greatest in segments with no contractile reserve and TME 0-25%.
The left ventricle, in addition to contractile function, also has the dual functions of synthesis and release of brain natriuretic peptide (BNP). Little is known about the relationship between TME and left ventricular synthesis and release of BNP and the subsequent BNP levels. However, TME may play an impactful role.
ceMRI has now enabled measurement of TME. Left ventricular synthesis and release of BNP can be assessed by blood BNP levels. The third study presented utilizes ceMRI to examine the relationships between TME and left ventricular synthesis and release of BNP. The relationships between regional contractile function, viable myocardium and ischemic myocardium with left ventricular synthesis and release of BNP were also explored. Fifty-nine patients underwent DbE and cardiac MRI and resting BNP levels were determined. By MRI, total extent of dysfunctional myocardium correlated strongest with BNP (r = 0.60, p<0.0001). The extent of scar, viability and ischemia also correlated. At DbE, a composite of dysfunctional and ischemic myocardium was the strongest correlate of BNP (r = 0.48, p<0.0001), with less strong correlations by global parameters. We concluded that the extent of dysfunctional myocardium, rather than its nature determines BNP levels.
We have shown that visual assessment of left ventricular wall motion can be objectively related to MRI measurements of thickening parameters. This adds to the validity of the technique for use in detection of resting regional dysfunction by MRI or 2DE and in DbE. Utilizing visual assessment of wall motion as well as measurement of TME by ceMRI, we have shown the following about the relationship between TME and left ventricular function. The likelihood of residual resting contractile function decreases with increasing TME but residual function is seen in many segments with >25% TME. The reduction of contractile reserve and thallium activity is comparable with increasing TME. TME is a major determinant of discordance between the DbE and Tl SPECT, but discordance is greatest in segments with no contractile reserve and TME 0-25%. And finally that it is the extent of dysfunctional myocardium, rather than whether the dysfunctional myocardium is made up of scar or VM, that determines left ventricular BNP synthesis and release function.