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J Am Coll Cardiol, 2008; 51:1784-1789, doi:10.1016/j.jacc.2008.01.036
© 2008 by the American College of Cardiology Foundation
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Cardiac Contractility Modulation Electrical Signals Improve Myocardial Gene Expression in Patients With Heart Failure

Christian Butter, MD*,*, Sharad Rastogi, MD{dagger}, Hans-Heinrich Minden, MD*, Jürgen Meyhöfer, MD*, Daniel Burkhoff, MD, PhD{ddagger} and Hani N. Sabbah, PhD{dagger}

* Heart Center Brandenburg in Bernau/Berlin, Bernau/Berlin, Germany
{dagger} Division of Cardiovascular Medicine, Henry Ford Health System, Detroit, Michigan
{ddagger} Columbia University, New York, New York.


Figure 1
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Figure 1 FIX-CHF-4 Study Design

This was a prospective, randomized, double-blind, double crossover study. FIX-CHF-4 = Fix-Chronic Heart Failure–4.

 

Figure 2
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Figure 2 Representative Northern Blots

Representative Northern blots from 2 patients, 1 from each treatment group. Differences in band intensities between periods of active and sham treatment are evident. The GAPDH band intensities show consistency of ribonucleic acid loading of the various lanes. ANP = A-type natriuretic peptides; BL = baseline; BNP = B-type natriuretic peptides; CCM = cardiac contractility modulation; GAPDH = glyceraldehyde-3-phosphate dehydrogenase; MHC = myosin heavy chain; PLB = phospholamban; p21 RAS = p21 Ras stretch receptor gene; p38MAPK = p38 mitogen activated protein kinase stretch receptor gene; RyR2 = ryanodine receptor; SERCA-2a = sarcoplasmic reticulum calcium adenosine triphosphatase.

 

Figure 3
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Figure 3 {alpha}-MHC Gene Expression

Changes in {alpha}-myosin heavy chain (MHC) gene expression (quantified as percent of baseline) at the end of study periods in group 1 (A) and group 2 (B) patients. (C) Data summarized by pooling of the end of ON periods from the 2 groups and end of OFF periods from the 2 groups. Solid lines show data from patients with idiopathic cardiomyopathy, whereas dashed lines are from patients with ischemic cardiomyopathy.

 

Figure 4
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Figure 4 Summary of Impact of CCM Signal Treatment on Gene Expression

Summary of impact of cardiac contractility modulation (CCM) signal treatment on expression of genes examined in this study. Data for each gene analyzed as summarized in text and in the legend of Figure 3. NCX = sodium-calcium exchanger; other abbreviations as in Figure 2.

 

Figure 5
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Figure 5 Correlations Between Gene Expression and Clinical Impact of CCM Signal Treatment

Percent changes in SERCA-2a expression were correlated with percent changes in peak VO 2 (A), Minnesota Living With Heart Failure Questionnaire (MLWHFQ) (B), and 6-min walk test (6MW) (C). Data included comparison of results from baseline to 3 to 6 months. DCM = idiopathic dilated cardiomyopathy; ICM = ischemic cardiomyopathy; other abbreviations as in Figure 2.

 




 
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