(Circulation. 1995;91:2717-2720.)
© 1995 American Heart Association, Inc.
Articles |
Reversal of Chronic Ventricular Dilation in Patients With End-Stage Cardiomyopathy by Prolonged Mechanical Unloading
From the Division of Circulatory Physiology, Department of Medicine, and the Division of Cardiothoracic Surgery, Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, NY.
Correspondence to Howard R. Levin, MD, Columbia-Presbyterian Medical Center, Division of Circulatory Physiology, 177 Fort Washington Ave, Milstein 5-435, New York, NY 10032.
Background Ventricular dilation, indexed by marked shifts toward larger volumes of the end-diastolic pressure-volume relation (EDPVR), has been considered to represent an irreversible aspect of ventricular remodeling in end-stage heart failure. However, we hypothesized that such dilation could be reversed with sufficient hemodynamic unloading, such as can be provided by a left ventricular assist device (LVAD).
Methods and Results The EDPVRs of hearts from seven patients with
end-stage idiopathic cardiomyopathy and comparable
baseline hemodynamics were measured ex vivo at the time of cardiac
transplantation; these were compared with EDPVRs from three normal
human hearts that were technically unsuitable for transplantation. Four
of the patients received optimal medical therapy; three of the
patients, who deteriorated on optimal therapy, underwent LVAD support
for 
4 months. Compared with the normal hearts, EDPVRs of hearts from
medically treated patients were shifted toward markedly larger volumes.
In contrast, EDPVRs of hearts from LVAD patients were similar to those
of normal hearts.
Conclusions Chronic hemodynamic unloading of sufficient magnitude and duration can result in reversal of chamber enlargement and normalization of cardiac structure as indexed by the EDPVR, both important aspects of remodeling, even in the most advanced stages of heart failure.
Key Words: diastole • heart failure • ventricles • cardiac volume
This article has been cited by other articles:
 |
|
 |
|
  M. Dandel, Y. Weng, H. Siniawski, E. Potapov, T. Drews, H. B. Lehmkuhl, C. Knosalla, and R. Hetzer Prediction of Cardiac Stability After Weaning From Left Ventricular Assist Devices in Patients With Idiopathic Dilated Cardiomyopathy Circulation, September 30, 2008; 118(14_suppl_1): S94 - S105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Beeri, C. Yosefy, J. L. Guerrero, F. Nesta, S. Abedat, M. Chaput, F. del Monte, M. D. Handschumacher, R. Stroud, S. Sullivan, et al. Mitral regurgitation augments post-myocardial infarction remodeling failure of hypertrophic compensation. J. Am. Coll. Cardiol., January 29, 2008; 51(4): 476 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Perrino, J. N. Schroder, B. Lima, N. Villamizar, J. J. Nienaber, C. A. Milano, and S. V. Naga Prasad Dynamic Regulation of Phosphoinositide 3-Kinase-{gamma} Activity and -Adrenergic Receptor Trafficking in End-Stage Human Heart Failure Circulation, November 27, 2007; 116(22): 2571 - 2579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Buckberg Congestive heart failure: Treat the disease, not the symptom Return to normalcy/Part II-The experimental approach. J. Thorac. Cardiovasc. Surg., October 1, 2007; 134(4): 844 - 849. [Full Text] [PDF]
|
|
|
|
|
|
J. Haft, W. Armstrong, D. B. Dyke, K. D. Aaronson, T. M. Koelling, D. J. Farrar, and F. D. Pagani Hemodynamic and Exercise Performance With Pulsatile and Continuous-Flow Left Ventricular Assist Devices Circulation, September 11, 2007; 116(11_suppl): I-8 - I-15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Beeri, C. Yosefy, J. L. Guerrero, S. Abedat, M. D. Handschumacher, R. E. Stroud, S. Sullivan, M. Chaput, D. Gilon, G. J. Vlahakes, et al. Early Repair of Moderate Ischemic Mitral Regurgitation Reverses Left Ventricular Remodeling: A Functional and Molecular Study Circulation, September 11, 2007; 116(11_suppl): I-288 - I-293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Shuros, R. W. Salo, V. G. Florea, J. Pastore, M. A. Kuskowski, Y. Chandrashekhar, and I. S. Anand Ventricular Preexcitation Modulates Strain and Attenuates Cardiac Remodeling in a Swine Model of Myocardial Infarction Circulation, September 4, 2007; 116(10): 1162 - 1169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Suzuki, T.-S. Li, A. Mikamo, M. Takahashi, M. Ohshima, M. Kubo, H. Ito, and K. Hamano The reduction of hemodynamic loading assists self-regeneration of the injured heart by increasing cell proliferation, inhibiting cell apoptosis, and inducing stem-cell recruitment J. Thorac. Cardiovasc. Surg., April 1, 2007; 133(4): 1051 - 1058. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Travis, G. A. Giridharan, G. M. Pantalos, R. D. Dowling, S. D. Prabhu, M. S. Slaughter, M. Sobieski, A. Undar, D. J. Farrar, and S. C. Koenig Vascular pulsatility in patients with a pulsatile- or continuous-flow ventricular assist device J. Thorac. Cardiovasc. Surg., February 1, 2007; 133(2): 517 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Klotz, J. Stypmann, H. Welp, C. Schmid, G. Drees, A. Rukosujew, and H. H. Scheld Does Continuous Flow Left Ventricular Assist Device Technology Have a Positive Impact on Outcome Pretransplant and Posttransplant? Ann. Thorac. Surg., November 1, 2006; 82(5): 1774 - 1778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Klotz, I. Hay, M. L. Dickstein, G.-H. Yi, J. Wang, M. S. Maurer, D. A. Kass, and D. Burkhoff Single-beat estimation of end-diastolic pressure-volume relationship: a novel method with potential for noninvasive application Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H403 - H412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Messas, A. Bel, M. C. Morichetti, C. Carrion, M. D. Handschumacher, S. Peyrard, J. T. Vilquin, M. Desnos, P. Bruneval, A. Carpentier, et al. Autologous Myoblast Transplantation for Chronic Ischemic Mitral Regurgitation J. Am. Coll. Cardiol., May 16, 2006; 47(10): 2086 - 2093. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Pandalai, C. F. Bulcao, W. H. Merrill, and S. A. Akhter Restoration of myocardial {beta}-adrenergic receptor signaling after left ventricular assist device support J. Thorac. Cardiovasc. Surg., May 1, 2006; 131(5): 975 - 980. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Heerdt, S. Klotz, and D. Burkhoff Cardiomyopathic Etiology and SERCA2a Reverse Remodeling During Mechanical Support of the Failing Human Heart Anesth. Analg., January 1, 2006; 102(1): 32 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wohlschlaeger, K. J. Schmitz, C. Schmid, K. W. Schmid, P. Keul, A. Takeda, S. Weis, B. Levkau, and H. A. Baba Reverse remodeling following insertion of left ventricular assist devices (LVAD): A review of the morphological and molecular changes Cardiovasc Res, December 1, 2005; 68(3): 376 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Olsson, F. Bredin, and A. Franco-Cereceda Echocardiographic findings using tissue velocity imaging following passive containment surgery with the Acorn CorCapTM cardiac support device Eur. J. Cardiothorac. Surg., September 1, 2005; 28(3): 448 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shirakawa, Y. Sawa, Y. Takewa, E. Tatsumi, Y. Kaneda, Y. Taenaka, and H. Matsuda Gene transfection with human hepatocyte growth factor complementary DNA plasmids attenuates cardiac remodeling after acute myocardial infarction in goat hearts implanted with ventricular assist devices J. Thorac. Cardiovasc. Surg., September 1, 2005; 130(3): 624 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dandel, Y. Weng, H. Siniawski, E. Potapov, H. B. Lehmkuhl, and R. Hetzer Long-Term Results in Patients With Idiopathic Dilated Cardiomyopathy After Weaning From Left Ventricular Assist Devices Circulation, August 30, 2005; 112(9_suppl): I-37 - I-45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Burkhoff, I. Mirsky, and H. Suga Assessment of systolic and diastolic ventricular properties via pressure-volume analysis: a guide for clinical, translational, and basic researchers Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H501 - H512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Mancini and D. Burkhoff Mechanical Device-Based Methods of Managing and Treating Heart Failure Circulation, July 19, 2005; 112(3): 438 - 448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Klotz, R. F. Foronjy, M. L. Dickstein, A. Gu, I. M. Garrelds, A.H. Jan Danser, M. C. Oz, J. D'Armiento, and D. Burkhoff Mechanical Unloading During Left Ventricular Assist Device Support Increases Left Ventricular Collagen Cross-Linking and Myocardial Stiffness Circulation, July 19, 2005; 112(3): 364 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Mann and M. R. Bristow Mechanisms and Models in Heart Failure: The Biomechanical Model and Beyond Circulation, May 31, 2005; 111(21): 2837 - 2849. [Full Text] [PDF]
|
|
|
|
|
|
S. Klotz, A. Barbone, S. Reiken, J. W. Holmes, Y. Naka, M. C. Oz, A. R. Marks, and D. Burkhoff Left ventricular assist device support normalizes left and right ventricular beta-adrenergic pathway properties J. Am. Coll. Cardiol., March 1, 2005; 45(5): 668 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Buckberg Imaging, models, and reality: A basis for anatomic-physiologic planning J. Thorac. Cardiovasc. Surg., February 1, 2005; 129(2): 243 - 245. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Pieske Reverse remodeling in heart failure - fact or fiction? Eur. Heart J. Suppl., August 1, 2004; 6(suppl_D): D66 - D78. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Klotz, M. C. Deng, J. Stypmann, J. Roetker, M. J. Wilhelm, D. Hammel, H. H. Scheld, and C. Schmid Left ventricular pressure and volume unloading during pulsatile versus nonpulsatile left ventricular assist device support Ann. Thorac. Surg., January 1, 2004; 77(1): 143 - 149. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Margulies Blocking Stretch-Induced Myocardial Remodeling Circ. Res., November 28, 2003; 93(11): 1020 - 1022. [Full Text] [PDF]
|
|
|
|
|
|
N. A. Nussmeier, C. B. Probert, D. Hirsch, J. R. Cooper Jr., I. D. Gregoric, T. J. Myers, and O. H. Frazier Anesthetic Management for Implantation of the Jarvik 2000TM Left Ventricular Assist System Anesth. Analg., October 1, 2003; 97(4): 964 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-l. He, J. Shimizu, G.-h. Yi, A. Gu, M. A. Kashem, D. L. Crabbe, S. Popilskis, E. X. Wu, W. P. Santamore, D. Melvin, et al. Left ventricular systolic performance in failing heart improved acutely by left ventricular reshaping J. Thorac. Cardiovasc. Surg., July 1, 2003; 126(1): 56 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. McGowan, C. B. Scott, A. Mu, R. J. McCormick, D. P. Thomas, and K. B. Margulies Unloading-induced remodeling in the normal and hypertrophic left ventricle Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H2061 - H2068. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Reiken, X. H.T. Wehrens, J. A. Vest, A. Barbone, S. Klotz, D. Mancini, D. Burkhoff, and A. R. Marks {beta}-Blockers Restore Calcium Release Channel Function and Improve Cardiac Muscle Performance in Human Heart Failure Circulation, May 20, 2003; 107(19): 2459 - 2466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Blaxall, B. M. Tschannen-Moran, C. A. Milano, and W. J. Koch Differential gene expression and genomic patient stratification following left ventricular assist device support J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1096 - 1106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Bristow Microarray measurements of gene expression before and after left ventricular assist device placement J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1107 - 1108. [Full Text] [PDF]
|
|
|
|
|
|
D. Burkhoff New heart failure therapy: The shape of things to come? J. Thorac. Cardiovasc. Surg., March 1, 2003; 125(90030): S50 - 52. [Full Text] [PDF]
|
|
|
|
|
|
N.E. Bowles The molecular biology of dilated cardiomyopathy Eur. Heart J. Suppl., December 1, 2002; 4(suppl_I): I2 - I7. [Abstract] [PDF]
|
|
|
|
|
|
M. S. Joharchi, U. Neiser, U. Lenschow, J. Schubert, W. Kienast, G. Noeldge-Schomburg, and G. Steinhoff Thoratec left ventricular assist device for bridging to recovery in fulminant acute myocarditis Ann. Thorac. Surg., July 1, 2002; 74(1): 234 - 235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. F. Saavedra, R. S. Tunin, N. Paolocci, T. Mishima, G. Suzuki, C. W. Emala, P. A. Chaudhry, P. Anagnostopoulos, R. C. Gupta, H. N. Sabbah, et al. Reverse remodeling and enhancedadrenergic reserve from passive externalsupport in experimental dilated heart failure J. Am. Coll. Cardiol., June 19, 2002; 39(12): 2069 - 2076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. Duncan Mechanical circulatory support for infants and children with cardiac disease Ann. Thorac. Surg., May 1, 2002; 73(5): 1670 - 1677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Heerdt, M. Schlame, R. Jehle, A. Barbone, D. Burkhoff, and T. J.J. Blanck Disease-specific remodeling of cardiac mitochondria after a left ventricular assist device Ann. Thorac. Surg., April 1, 2002; 73(4): 1216 - 1221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. de Jonge, D. F. van Wichen, M. E. I. Schipper, J. R. Lahpor, F. H. J. Gmelig-Meyling, E. O. Robles de Medina, and R. A. de Weger Left ventricular assist device in end-stage heart failure: persistence of structural myocyte damage after unloading: An immunohistochemical analysis of the contractile myofilaments J. Am. Coll. Cardiol., March 20, 2002; 39(6): 963 - 969. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. L. Janssen, G. Hasenfuss, O. Zeitz, S. E. Lehnart, J. Prestle, D. Darmer, J. Holtz, and H. Schumann Load-dependent induction of apoptosis in multicellular myocardial preparations Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H349 - H356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Barbone, M. C. Oz, D. Burkhoff, and J. W. Holmes Normalized Diastolic Properties After Left Ventricular Assist Result From Reverse Remodeling of Chamber Geometry Circulation, September 18, 2001; 104(90001): I-229 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Mann and H. Taegtmeyer Dynamic Regulation of the Extracellular Matrix After Mechanical Unloading of the Failing Human Heart: Recovering the Missing Link in Left Ventricular Remodeling Circulation, September 4, 2001; 104(10): 1089 - 1091. [Full Text] [PDF]
|
|
|
|
|
|
Y. Y. Li, Y. Feng, C. F. McTiernan, W. Pei, C. S. Moravec, P. Wang, W. Rosenblum, R. L. Kormos, and A. M. Feldman Downregulation of Matrix Metalloproteinases and Reduction in Collagen Damage in the Failing Human Heart After Support With Left Ventricular Assist Devices Circulation, September 4, 2001; 104(10): 1147 - 1152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Burkhoff New heart failure therapy: The shape of things to come? J. Thorac. Cardiovasc. Surg., September 1, 2001; 122(3): 421 - 423. [Full Text] [PDF]
|
|
|
|
|
|
B. W. Duncan, D. J. Bohn, A. M. Atz, J. W. French, P. C. Laussen, and D. L. Wessel Mechanical circulatory support for the treatment of children with acute fulminant myocarditis J. Thorac. Cardiovasc. Surg., September 1, 2001; 122(3): 440 - 448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Ogletree-Hughes, L. B. Stull, W. E. Sweet, N. G. Smedira, P. M. McCarthy, and C. S. Moravec Mechanical Unloading Restores {beta}-Adrenergic Responsiveness and Reverses Receptor Downregulation in the Failing Human Heart Circulation, August 21, 2001; 104(8): 881 - 886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Barbone, J. W. Holmes, P. M. Heerdt, A. H.S. The', Y. Naka, N. Joshi, M. Daines, A. R. Marks, M. C. Oz, and D. Burkhoff Comparison of Right and Left Ventricular Responses to Left Ventricular Assist Device Support in Patients With Severe Heart Failure: A Primary Role of Mechanical Unloading Underlying Reverse Remodeling Circulation, August 7, 2001; 104(6): 670 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. W. Guldner, P. Klapproth, M. Gro{beta}herr, A. Brugge, A. Sheikhzadeh, R. Tolg, E. Rumpel, R. Noel, and H.-H. Sievers Biomechanical Hearts: Muscular Blood Pumps, Performed in a 1-Step Operation, and Trained Under Support of Clenbuterol Circulation, August 7, 2001; 104(6): 717 - 722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Madigan, A. Barbone, A. F. Choudhri, D. L. S. Morales, B. Cai, M. C. Oz, and D. Burkhoff Time course of reverse remodeling of the left ventricle during support with a left ventricular assist device J. Thorac. Cardiovasc. Surg., May 1, 2001; 121(5): 902 - 908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Kumpati, P. M. McCarthy, and K. J. Hoercher Left ventricular assist device bridge to recovery: a review of the current status Ann. Thorac. Surg., March 1, 2001; 71 (2007): S103 - S108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Brower and J. S. Janicki Contribution of ventricular remodeling to pathogenesis of heart failure in rats Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H674 - H683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Slaughter, M. A. Silver, D. J. Farrar, A. J. Tatooles, and P. S. Pappas A new method of monitoring recovery and weaning the thoratec left ventricular assist device Ann. Thorac. Surg., January 1, 2001; 71(1): 215 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Heerdt, J. W. Holmes, B. Cai, A. Barbone, J. D. Madigan, S. Reiken, D. L. Lee, M. C. Oz, A. R. Marks, and D. Burkhoff Chronic Unloading by Left Ventricular Assist Device Reverses Contractile Dysfunction and Alters Gene Expression in End-Stage Heart Failure Circulation, November 28, 2000; 102(22): 2713 - 2719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mital, K. E. Loke, L. J. Addonizio, M. C. Oz, and T. H. Hintze Left ventricular assist device implantation augments nitric oxide dependent control of mitochondrial respiration in failing human hearts J. Am. Coll. Cardiol., November 15, 2000; 36(6): 1897 - 1902. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Hetzer, J. H. Muller, Y.-G. Weng, M. Loebe, and G. Wallukat Midterm follow-up of patients who underwent removal of a left ventricular assist device after cardiac recovery from end-stage dilated cardiomyopathy J. Thorac. Cardiovasc. Surg., November 1, 2000; 120(5): 843 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A.K. Beyer, D. M. McMullan, R. Delgado, I. Gregoric, B. Radovancevic, and O.H. Frazier Normalization of native heart function years after heterotopic transplantation Ann. Thorac. Surg., November 1, 2000; 70(5): 1690 - 1691. [Abstract] [Full Text] [PDF]
|
|