Cardiovascular magnetic resonance of myocardial viability
Kaandorp, T.A.M.
Citation
Kaandorp, T. A. M. (2007, March 14). Cardiovascular magnetic resonance of myocardial
viability. Department Radiology, Faculty of Medicine / Leiden University Medical Center(LUMC), Leiden University. Retrieved from https://hdl.handle.net/1887/11409
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Institutional Repository of the University of Leiden
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131
9 Prediction of beneficial effect of ß-blocker
therapy in severe ischemic
cardiomyopathy: assessment of global left
ventricular ejection fraction using
dobutamine stress cardiovascular magnetic
resonance imaging
TA Kaandorp, HJ Lamb, JJ Bax, E Boe rs ma, EP Vi e rge ve r,
EE van de r W al l , A de Roos
He art 2005; 91: 1471- 2
Abstract
Objective:To evaluate the feasibility for prediction of E-blocker therapy effect on global left ventricular ejection fraction (LVEF),by measurement of globalLVEF during low- dose dobutamine magnetic resonance imaging (MRI), before therapy, in patients with severe ischemic cardiomyopathy. Design: Prospective study. Setting: Tertiary referral centre. Patients: 20 consecutive patients with chronic coronary artery disease and ejection fraction <40%. Interventions: All patients received ß-blocker therapy. Main outcome measures: MRI was performed at rest and during low-dose dobutamine stress before starting carvedilol therapy and at follow up to assess global LVEF.
Additionally, a NYHA classification was assessed by the patient's cardiologist before and after ß-blocker therapy. Results: Global LVEF at follow up may be predicted by using the formula: E-blocker induced LVEF improvement = 0.66 * (LVEFstress- LVEFrest) + 0.34 (r2 = 0.67, p<0.01). An induced improvement in LVEF t7% may predict a positive response t5% at follow up. This improvement was consistent with the NYHA classification before and after ß-blocker therapy. Conclusion:Therapy effect of carvedilol may be predicted at baseline by assessment of global LVEF at rest and during low-dose dobutamine stress. Therefore, MRI may be helpful to select patients who benefit from E-blocker therapy.
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Introduction
Patients with severe ischemic cardiomyopathy have a combination of viable and non- viable myocardium. In the presence of substantial ischemic, but viable myocardium, ß- blocker therapy may improve left ventricular ejection fraction (LVEF) due to a reduction in oxygen consumption and a restoration of ß-adrenergic signaling pathways. However, not all patients show a positive response to this therapy 1 and can suffer from side effects 2. Therefore, it is desirable to identify patients with high likelihood of beneficial response to ß-blockers.
Models currently used to detect viable myocardium are based upon segmental analysis. Dobutamine induced segmental improvement before therapy is suggested to have a relationship between regional contractile reserve and improvement in global LVEF after ß-blocker therapy. However, improvement of remote tissue is not evaluated and this may also contribute to improvement of LVEF after therapy. Thus, direct measurement of LVEF during low-dose dobutamine stimulation may represent contractile reserve of the entire left ventricle.
Cardiovascular magnetic resonance imaging (MRI) is a highly reproducible, validated and observer independent imaging method for measurement of global LVEF, and can be used to evaluate LVEF at rest as well as during dobutamine stress.
Furthermore, Bellenger and coworkers described that calculated sample sizes for assessment of LVEF for MRI were substantially smaller than recently published values for ultrasound. Measurement of a change in LVEF of 3% required only 15 patients 3.
Accordingly, the purpose of the present study was to evaluate the feasibility for prediction of E-blocker therapy effect on LVEF, by MRI measurement of LVEF during low-dose dobutamine, in patients with severe ischemic cardiomyopathy.
M aterial and methods
Patients with chronic stable coronary artery disease (CAD) (n=26, mean age 64 years, all men) and LVEF <40% on Tc-99m-SPECT at rest, were enrolled consecutively.
Due to side effects 3 patients refused to continue therapy, 2 appeared claustrophobic at follow up and 1 was unwilling to undergo repeated MRI. Previous myocardial infarction was present in all of the patients (>4 months before entrance into the study). All patients had significant CAD on angiography (>70% reduction in luminal diameter) and had an average of 2.1 ± 1 stenosed vessels. Patients did not qualify or
Prediction of ß -blocker effect on LVEF by MRI
133 undergo revascularization therapy because: 1. Patients had poor target vessels; 2.
Patients did not qualify for revascularization because of prior existing co-morbidity; 3.
Patients refused to undergo revascularization. Carvedilol was started at an initial dose of 3.125 mg twice daily and was subsequently titrated, at one-week intervals as tolerated, up to a target dose of 25 mg twice daily 4. Other medications: diuretics 90%, anticoagulants 100%, angiotensin converting enzyme inhibitors 56%, nitrates 29%, digoxin 35%, calcium inhibitors 18%, lipid lowering agents 65%. The congestive heart failure classification by the New York Heart Association (NYHA) was determined at baseline and follow up by the patient's cardiologist, unaware of the MRI data.
Patients were studied by MRI before starting therapy and at follow up. LVEF was determined at rest and during low-dose dobutamine stress (10 µg/kg/min) before starting therapy. Each patient gave informed consent to the study protocol that was approved by the local ethics committee.
A 1.5-Tesla MRI system (Philips Medical Systems, The Netherlands) with 5- element synergy coil and vector electrocardiographic gating were used. The entire heart was imaged in short-axis view during multiple 15-second breath-holds, using a Steady-State Free-Precession sequence (field of view 400 x 400 mm, matrix size 256 x 256, slice thickness 10.00 mm). MRI images were analyzed on a remote workstation.
LVEF was calculated using MASS software (Medis, The Netherlands).
Reported data are expressed as mean values ± 1 standard deviation (SD).
Responders to ß-blocker therapy were defined as having an improvement in LVEF at rest t5% between baseline and follow up 5. Differences in LVEF during dobutamine stress versus LVEF at rest, both before therapy, and LVEF at follow up versus LVEF at rest before therapy, were calculated. To assess intra- and interobserver agreements, 12 patients were reanalyzed and intraclass correlation coefficients (ICC) were calculated. Linear regression analysis was performed to determine the relation between these differences. W hen applicable, paired two-tailed Student's t test were used, otherwise, two-sample two-tailed Student's t test were used. A p-value <0.05 was considered statistically significant.
Results
Of the 20 remaining patients, ß-blocker therapy was tolerated and their target dose was reached, other medication remained unchanged. The intra- and interobserver reliability of the LVEF measurement was excellent (ICC=0.97 and 0.99, respectively).
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In all patients, mean (SD) LVEF at baseline before carvedilol therapy was 31 (8)% at rest (mean (SD) LVEF according to SPECT was 29 (7)%), increasing to 40 (9)% (p<0.01) during dobutamine infusion. After an average (SD) of 7 (4) months of carvedilol therapy, mean (SD) LVEF at rest had improved to 37 (9)% (p<0.01, compared to baseline LVEF at rest). All patients had significant CAD on angiography with an average (SD) of 2.1 (1) stenosed vessels.
In responders (n=15), mean (SD) LVEF had improved from 32 (8)% at baseline to 40 (8)% (p<0.01) at follow up, whereas non-responders (n=5) showed negligible improvement between baseline (28 (6)%) and follow up (29 (5)%, p>0.05). During dobutamine, mean (SD) LVEF in responders increased to 42 (8)%; in non-responders to 31 (6)% (Figure 1A). Figure 1B shows the relation between LVEF change due to low-dose dobutamine stress at baseline and therapy effect at follow up. Carvedilol therapeutic effect can be predicted at baseline by using the formula: E-blocker induced LVEF improvement = 0.66 * (LVEFstress-LVEFrest) + 0.34 (r2=0.67, p<0.01). An induced improvement in LVEF t7% predicts a positive response t5% at follow up.
In responders, the average (SD) NYHA improved from 2.3 (0.5) at baseline to 1.8 (0.6) at follow up (p<0.05), whereas in non-responders the average (SD) NYHA did not change (2 (0) to 2 (0), non-significant).
Discussion
In this preliminary study, we demonstrate the feasibility of MRI to predict ß-blocker therapy effect in patients with severe ischemic cardiomyopathy. The present study shows that LVEF as determined during low-dose dobutamine MRI before therapy, can predict the increase in LVEF after ß-blocker therapy in patients with severe ischemic cardiomyopathy (Figure 1B).
Currently, only contractile reserve in segments with wall motion abnormalities at rest is evaluated. With MRI measurement of LVEF during dobutamine infusion, contractile reserve of the entire left ventricle is evaluated. Due to the high reproducibility, MRI is able to detect even small changes in the patients LVEF 3. To our knowledge, this is the first such study to predict response to ß-blockers therapy with MRI assessment of LVEF during dobutamine infusion.
The small number of patients is a limiting factor; a larger prospective study is needed to prove the validity of the prediction rule and to extend the current observations on improvement in NYHA class.
Prediction of ß -blocker effect on LVEF by MRI
135 Figure 1. (A). Comparison of responders and non-responders to carvedilol treatment, showing the effect of low-dose dobutamine stress before starting treatment. Note the increase in left ventricular ejection fraction (LVEF) during dobutamine infusion at baseline in responders (p<0.01), as compared to the modest improvement in non-responders (p>0.05). (B). Linear regression analysis of the difference in LVEF during dobutamine stress versus LVEF at rest, both before treatment, and the difference in LVEF at follow up versus LVEF at rest before treatment.
LVEFfollow up– LVEFrest (%)
Predictive cut off y = 0.66*(LVEFstress–LVEFrest) +0.34 r2 = 0.67
p < 0.01
LVEFstress–LVEFrest(%)
10 15
5 7
15
10
5
0 B
A N on-responders
Responders
Stress Rest
Rest Stress
LVEF (%)
60
40 50
30 20 10 0
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136
Acknowledgements
This work was supported by The Netherlands Organization for Scientific Research (NWO), grant number 902-37-124 (H. J. Lamb, Leiden, The Netherlands).
References
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2. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N.Engl.J.Med. 1996;334:1349-55.
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