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J Am Coll Cardiol, 2000; 35:569-582
© 2000 by the American College of Cardiology Foundation
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REVIEW ARTICLES

Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling

Jay N. Cohn, MD*, Roberto Ferrari, MD{dagger}, Norman Sharpe, MD{ddagger} on Behalf of an International Forum on Cardiac Remodeling

* Department of Medicine, Cardiovascular Division, University of Minnesota Medical School, Minneapolis, Minnesota, USA
{dagger} Cattedra di Cardiologia, Universita degli Studi di Ferrara, Ferrara, Italy
{ddagger} Department of Medicine and Health Sciences, University of Auckland School of Medicine, Auckland, New Zealand

Manuscript received June 3, 1999; revised manuscript received October 15, 1999, accepted November 18, 1999.

Reprint requests and correspondence: Dr. Jay N. Cohn, Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, 420 Delaware Street, SE—Box 508 UMHC, Minneapolis, Minnesota 55455

Cardiac remodeling is generally accepted as a determinant of the clinical course of heart failure (HF). Defined as genome expression resulting in molecular, cellular and interstitial changes and manifested clinically as changes in size, shape and function of the heart resulting from cardiac load or injury, cardiac remodeling is influenced by hemodynamic load, neurohormonal activation and other factors still under investigation.

Although patients with major remodeling demonstrate progressive worsening of cardiac function, slowing or reversing remodeling has only recently become a goal of HF therapy. Mechanisms other than remodeling can also influence the course of heart disease, and disease progression may occur in other ways in the absence of cardiac remodeling.

Left ventricular end-diastolic and end-systolic volume and ejection fraction data provide support for the beneficial effects of therapeutic agents such as angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic blocking agents on the remodeling process. These agents also provide benefits in terms of morbidity and mortality. Although measurement of ejection fraction can reliably guide initiation of treatment in HF, opinions differ regarding the value of ejection fraction data in guiding ongoing therapy. The role of echocardiography or radionuclide imaging in the management and monitoring of HF is as yet unclear.

To fully appreciate the potential benefits of HF therapies, clinicians should understand the relationship between remodeling and HF progression. Their patients may then, in turn, acquire an improved understanding of their disease and the treatments they are given.

Abbreviations and Acronyms
  ACE = angiotensin-converting enzyme
  AIRE = Acute Infarction Ramipril Evaluation Study
  ANP = atrial natriuretic peptide
  ANZ = Australia/New Zealand Collaborative Group
  CIBIS II = Cardiac Insufficiency Bisoprolol Study
  ECG = electrocardiogram
  HF = heart failure
  LV = left ventricular
  MDC = Metropol Dilated Cardiomyopathy trial
  MERIT-HF = Metoprolol CR/XL Randomized Intervention Trial in Heart Failure
  MI = myocardial infarction
  MRI = magnetic resonance imaging
  NO = nitric oxide
  RAS = renin angiotensin system
  SAVE = Survival and Ventricular Enlargement Study
  SNS = sympathetic nervous system
  SOLVD = Studies of Left Ventricular Dysfunction
  TBARS = thiobarbituric acid reactive substances
  TNF = tumor necrosis factor
  TRACE = Trandolapril Cardiac Evaluation Study
  V-HeFT I and V-HeFT II = Vasodilator Heart Failure Trials




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R. Hetzer, M. Dandel, C. Knosalla, J. G. Burniston, V. G. Florea, D. Rott, D. Leibowitz, G. J. Vanderwilt, M. H. Yacoub, and E. J. Birks
Left Ventricular Assist Devices and Drug Therapy in Heart Failure
N. Engl. J. Med., February 22, 2007; 356(8): 869 - 872.
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 JNMHome page
V. Dilsizian, W. C. Eckelman, M. L. Loredo, E. M. Jagoda, and J. Shirani
Evidence for Tissue Angiotensin-Converting Enzyme in Explanted Hearts of Ischemic Cardiomyopathy Using Targeted Radiotracer Technique
J. Nucl. Med., February 1, 2007; 48(2): 182 - 187.
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 Eur J Heart FailHome page
J. Abdulla, S. Barlera, R. Latini, L. Kjoller-Hansen, P. Sogaard, E. Christensen, L. Kober, and C. Torp-Pedersen
A systematic review: Effect of angiotensin converting enzyme inhibition on left ventricular volumes and ejection fraction in patients with a myocardial infarction and in patients with left ventricular dysfunction
Eur J Heart Fail, February 1, 2007; 9(2): 129 - 135.
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 HeartHome page
S. De Castro, S. Caselli, M. Maron, A. Pelliccia, E. Cavarretta, P. Maddukuri, D. Cartoni, E. Di Angelantonio, J. T Kuvin, A. R Patel, et al.
Left ventricular remodelling index (LVRI) in various pathophysiological conditions: a real-time three-dimensional echocardiographic study
Heart, February 1, 2007; 93(2): 205 - 209.
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 Eur J Heart FailHome page
L. M. D. Stefano, L. S. Matsubara, and B. B. Matsubara
Myocardial dysfunction with increased ventricular compliance in volume overload hypertrophy
Eur J Heart Fail, December 1, 2006; 8(8): 784 - 789.
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 Am. J. Physiol. Heart Circ. Physiol.Home page
A. N. Mazzadi, X. Andre-Fouet, N. Costes, P. Croisille, D. Revel, and M. F. Janier
Mechanisms leading to reversible mechanical dysfunction in severe CAD: alternatives to myocardial stunning
Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2570 - H2582.
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 J. Thorac. Cardiovasc. Surg.Home page
A. Kilic, T. Li, T. D.C. Nolan, J. R. Nash, S. Li, D. J. Prastein, G. Schwartzbauer, S. L. Moainie, G. K. Yankey, C. DeFilippi, et al.
Strain-related regional alterations of calcium-handling proteins in myocardial remodeling
J. Thorac. Cardiovasc. Surg., October 1, 2006; 132(4): 900 - 908.
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 Eur J Heart FailHome page
E. Biagini, M. Valgimigli, P. C. Smits, D. Poldermans, A. F.L. Schinkel, V. Rizzello, E. E.M. Onderwater-, M. Bountioukos, and P. W. Serruys
Stress and tissue Doppler echocardiographic evidence of effectiveness of myoblast transplantation in patients with ischaemic heart failure
Eur J Heart Fail, October 1, 2006; 8(6): 641 - 648.
[Abstract] [Full Text] [PDF]

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 HeartHome page
K Debl, B Djavidani, S Buchner, C Lipke, W Nitz, S Feuerbach, G Riegger, and A Luchner
Delayed hyperenhancement in magnetic resonance imaging of left ventricular hypertrophy caused by aortic stenosis and hypertrophic cardiomyopathy: visualisation of focal fibrosis
Heart, October 1, 2006; 92(10): 1447 - 1451.
[Abstract] [Full Text] [PDF]

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 HeartHome page
S Kasama, T Toyama, T Hatori, H Sumino, H Kumakura, Y Takayama, S Ichikawa, T Suzuki, and M Kurabayashi
Effects of torasemide on cardiac sympathetic nerve activity and left ventricular remodelling in patients with congestive heart failure
Heart, October 1, 2006; 92(10): 1434 - 1440.
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 Anesth. Analg.Home page
L. Groban and J. Butterworth
Perioperative management of chronic heart failure.
Anesth. Analg., September 1, 2006; 103(3): 557 - 575.
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 Eur Heart J SupplHome page
E. Roig
Usefulness of neurohormonal markers in the diagnosis and prognosis of heart failure
Eur. Heart J. Suppl., September 1, 2006; 8(suppl_E): E12 - E17.
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 Eur J Heart FailHome page
J. Abdulla, L. Kober, E. Christensen, and C. Torp-Pedersen
Effect of beta-blocker therapy on functional status in patients with heart failure -- A meta-analysis
Eur J Heart Fail, August 1, 2006; 8(5): 522 - 531.
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 J Am Coll CardiolHome page
M. P. Hudson, P. W. Armstrong, W. Ruzyllo, J. Brum, L. Cusmano, P. Krzeski, R. Lyon, M. Quinones, P. Theroux, D. Sydlowski, et al.
Effects of Selective Matrix Metalloproteinase Inhibitor (PG-116800) to Prevent Ventricular Remodeling After Myocardial Infarction: Results of the PREMIER (Prevention of Myocardial Infarction Early Remodeling) Trial
J. Am. Coll. Cardiol., July 4, 2006; 48(1): 15 - 20.
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 CirculationHome page
A. T. Yan, A. J. Shayne, K. A. Brown, S. N. Gupta, C. W. Chan, T. M. Luu, M. F. Di Carli, H. G. Reynolds, W. G. Stevenson, and R. Y. Kwong
Characterization of the Peri-Infarct Zone by Contrast-Enhanced Cardiac Magnetic Resonance Imaging Is a Powerful Predictor of Post-Myocardial Infarction Mortality
Circulation, July 4, 2006; 114(1): 32 - 39.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
V. A. Cameron, T. J. Mocatta, A. P. Pilbrow, C. M. Frampton, R. W. Troughton, A. M. Richards, and C. C. Winterbourn
Angiotensin Type-1 Receptor A1166C Gene Polymorphism Correlates With Oxidative Stress Levels in Human Heart Failure
Hypertension, June 1, 2006; 47(6): 1155 - 1161.
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 Am. J. Respir. Crit. Care Med.Home page
K. Usui, J. D. Parker, G. E. Newton, J. S. Floras, C. M. Ryan, and T. D. Bradley
Left Ventricular Structural Adaptations to Obstructive Sleep Apnea in Dilated Cardiomyopathy
Am. J. Respir. Crit. Care Med., May 15, 2006; 173(10): 1170 - 1175.
[Abstract] [Full Text] [PDF]

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 Eur Heart JHome page
E. Donal, C. Leclercq, C. Linde, and J.-C. Daubert
Effects of cardiac resynchronization therapy on disease progression in chronic heart failure
Eur. Heart J., May 1, 2006; 27(9): 1018 - 1025.
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 HeartHome page
S Kasama, T Toyama, T Hatori, H Sumino, H Kumakura, Y Takayama, S Ichikawa, T Suzuki, and M Kurabayashi
Comparative effects of valsartan and enalapril on cardiac sympathetic nerve activity and plasma brain natriuretic peptide in patients with congestive heart failure
Heart, May 1, 2006; 92(5): 625 - 630.
[Abstract] [Full Text] [PDF]

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 Arch Intern MedHome page
A. Goldberg, H. Hammerman, S. Petcherski, M. Nassar, A. Zdorovyak, S. Yalonetsky, M. Kapeliovich, Y. Agmon, R. Beyar, W. Markiewicz, et al.
Hyponatremia and Long-term Mortality in Survivors of Acute ST-Elevation Myocardial Infarction.
Arch Intern Med, April 10, 2006; 166(7): 781 - 786.
[Abstract] [Full Text] [PDF]

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 J. Thorac. Cardiovasc. Surg.Home page
J. J. Gavira, J. Herreros, A. Perez, M. J. Garcia-Velloso, J. Barba, F. Martin-Herrero, C. Canizo, A. Martin-Arnau, J. M. Marti-Climent, M. Hernandez, et al.
Autologous skeletal myoblast transplantation in patients with nonacute myocardial infarction: 1-year follow-up
J. Thorac. Cardiovasc. Surg., April 1, 2006; 131(4): 799 - 804.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
M. Suleiman, R. Khatib, Y. Agmon, R. Mahamid, M. Boulos, M. Kapeliovich, Y. Levy, R. Beyar, W. Markiewicz, H. Hammerman, et al.
Early Inflammation and Risk of Long-Term Development of Heart Failure and Mortality in Survivors of Acute Myocardial Infarction: Predictive Role of C-Reactive Protein
J. Am. Coll. Cardiol., March 7, 2006; 47(5): 962 - 968.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
E. Carluccio, P. Biagioli, G. Alunni, A. Murrone, C. Giombolini, T. Ragni, P. N. Marino, G. Reboldi, and G. Ambrosio
Patients With Hibernating Myocardium Show Altered Left Ventricular Volumes and Shape, Which Revert After Revascularization: Evidence That Dyssynergy Might Directly Induce Cardiac Remodeling
J. Am. Coll. Cardiol., March 7, 2006; 47(5): 969 - 977.
[Abstract] [Full Text] [PDF]


 
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