This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Vanderheyden, M. Articles by Bartunek, J. Search for Related Content PubMed Articles by Vanderheyden, M. Articles by Bartunek, J. Related Collections Related Articles

CLINICAL RESEARCH: HEART FAILURE AND RESYNCHRONIZATION

Myocardial Gene Expression in Heart Failure Patients Treated With Cardiac Resynchronization Therapy

Responders Versus Nonresponders

Cardiovascular Center, Molecular Cardiology Unit and Cardiovascular Research Center, Onze Lieve Vrouw Ziekenhuis, Aalst, Belgium.

Manuscript received March 29, 2007; revised manuscript received July 2, 2007, accepted July 3, 2007.

^_* Reprint requests and correspondence: Dr. Marc Vanderheyden, Cardiovascular Center, Onze Lieve Vrouw Ziekenhuis, Moorselbaan 164, 9400 Aalst, Belgium. (Email: marc.vanderheyden{at}olvz-aalst.be).

Objectives: We studied whether functional improvement after cardiac resynchronization therapy (CRT) is associated with reversal of the heart failure (HF) gene program.

Background: Cardiac resynchronization therapy improves exercise tolerance and survival in patients with advanced congestive HF and dyssynchrony.

Methods: Twenty-four patients referred for CRT underwent left ventricular (LV) endomyocardial biopsies immediately before CRT implantation (baseline). In addition, 17 of them underwent LV endomyocardial biopsy procurement 4 months later (follow-up). In 6 control patients with normal LV function, LV biopsies were obtained at the time of coronary artery bypass grafting. The LV messenger ribonucleic acid (mRNA) levels of contractile and calcium regulatory genes were measured by quantitative real time polymerase chain reaction and normalized for glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The HF patients showing an improvement in New York Heart Association (NYHA) functional class by >1 score and a relative increase in LV ejection fraction 25% at 4 months after CRT were considered as responders.

Results: The HF patients were characterized by lower LV mRNA levels of -myosin heavy chain (-MHC), β-myosin heavy chain (β-MHC), sarcoplasmic reticulum calcium ATPase 2 (SERCA), phospholamban (PLN), and higher brain natriuretic peptide (BNP) mRNA levels as compared with control subjects. Responders to CRT (n = 11) showed an increase in LVEF (p < 0.001), a decrease in left ventricular end-diastolic diameter (p = 0.003), and NYHA functional class (p = 0.002), and a reduction in N-terminal proBNP levels (p = 0.032) as compared with baseline. This was associated with an increase in mRNA levels of -MHC (p = 0.035), SERCA (p = 0.032), a decrease in BNP mRNA levels (p = 0.002), and an increase in the ratio of -/β-MHC (p = 0.018) and SERCA/PLN (p = 0.012). No significant changes in molecular profile were observed in nonresponders.

Conclusions: In HF patients with electromechanical cardiac dyssynchrony, functional improvement related to CRT is associated with favorable changes in established molecular markers of HF, including genes that regulate contractile function and pathologic hypertrophy.

Abbreviations and Acronyms   BNP = brain natriuretic peptide   CRT = cardiac resynchronization therapy   HF = heart failure   LV = left ventricle/ventricular   MHC = myosin heavy chain   mRNA = messenger ribonucleic acid   Nt-proBNP = N-terminal part of the pro-brain natriuretic peptide   PLN = phospholamban   RT-PCR = real-time polymerase chain reaction   SERCA = sarcoplasmic reticulum calcium ATPase 2

Related Articles

Molecular Remodeling in Human Heart Failure

Thomas P. Cappola
J. Am. Coll. Cardiol. 2008 51: 137-138. [Full Text] [PDF]

This article has been cited by other articles:

				K. Chakir, S. K. Daya, T. Aiba, R. S. Tunin, V. L. Dimaano, T. P. Abraham, K. Jaques, E. W. Lai, K. Pacak, W.-Z. Zhu, et al. Mechanisms of Enhanced {beta}-Adrenergic Reserve From Cardiac Resynchronization Therapy Circulation, March 10, 2009; 119(9): 1231 - 1240. [Abstract] [Full Text] [PDF]

				T. Aiba, G. G. Hesketh, A. S. Barth, T. Liu, S. Daya, K. Chakir, V. L. Dimaano, T. P. Abraham, B. O'Rourke, F. G. Akar, et al. Electrophysiological Consequences of Dyssynchronous Heart Failure and Its Restoration by Resynchronization Therapy Circulation, March 10, 2009; 119(9): 1220 - 1230. [Abstract] [Full Text] [PDF]

				M. Vanderheyden and J. Bartunek Cardiac Resynchronization Therapy in Dyssynchronous Heart Failure: Zooming in on Cellular and Molecular Mechanisms Circulation, March 10, 2009; 119(9): 1192 - 1194. [Full Text] [PDF]

				W. Mullens, R. A. Grimm, T. Verga, T. Dresing, R. C. Starling, B. L. Wilkoff, and W.H. W. Tang Insights from a cardiac resynchronization optimization clinic as part of a heart failure disease management program. J. Am. Coll. Cardiol., March 3, 2009; 53(9): 765 - 773. [Abstract] [Full Text] [PDF]

				W. Mullens, T. Verga, R. A. Grimm, R. C. Starling, B. L. Wilkoff, and W.H. W. Tang Persistent hemodynamic benefits of cardiac resynchronization therapy with disease progression in advanced heart failure. J. Am. Coll. Cardiol., February 17, 2009; 53(7): 600 - 607. [Abstract] [Full Text] [PDF]

				W.H. W. Tang and G. S. Francis The Year in Heart Failure J. Am. Coll. Cardiol., November 11, 2008; 52(20): 1671 - 1678. [Full Text] [PDF]

				J. Bartunek and M. Vanderheyden Cardiac Dyssynchrony in Congestive Heart Failure and Atrial Fibrillation: Integrating Regularization and Resynchronization J. Am. Coll. Cardiol., October 7, 2008; 52(15): 1247 - 1249. [Full Text] [PDF]

				T. Aiba, A. Barth, and G. F. Tomaselli Deciphering Gene Expression Profiling in Cardiac Resynchronization Therapy J. Am. Coll. Cardiol., September 30, 2008; 52(14): 1177 - 1177. [Full Text] [PDF]

				M. Vanderheyden, W. Mullens, and J. Bartunek Reply J. Am. Coll. Cardiol., September 30, 2008; 52(14): 1177 - 1178. [Full Text] [PDF]

				A. Auricchio and F. W. Prinzen Update on the pathophysiological basics of cardiac resynchronization therapy Europace, July 1, 2008; 10(7): 797 - 800. [Abstract] [Full Text] [PDF]

				T. P. Cappola Molecular Remodeling in Human Heart Failure J. Am. Coll. Cardiol., January 15, 2008; 51(2): 137 - 138. [Full Text] [PDF]