CLINICAL STUDY: HEART FAILURE
Increased myocardial apoptosis in patients with unfavorable left ventricular remodeling and early symptomatic post-infarction heart failure
Antonio Abbate, MD*,*,
Giuseppe G. L. Biondi-Zoccai, MD*,
Rossana Bussani, MD ,
Aldo Dobrina, MD ,
Debora Camilot, MD,
Florinda Feroce, MD ,
Raffaele Rossiello, MD,
Feliciano Baldi, MD,
Furio Silvestri, MD,
Luigi M. Biasucci, MD, FACC* and
Alfonso Baldi, MD
* Institute of Cardiology, Catholic University of the Sacred Heart, Rome, Italy
Department of Pathologic Anatomy, University of Trieste, Trieste, Italy
Department of Physiology and Pathology, University of Trieste, Trieste, Italy
Department of Biochemistry and Biophysics "F. Cedrangolo", Section of Pathologic Anatomy, Second University of Naples, Naples, Italy
Manuscript received July 2, 2002;
revised manuscript received November 1, 2002,
accepted November 19, 2002.
* Reprint requests and correspondence: Dr. Antonio Abbate, Catholic University of Rome, Institute of Cardiology, Largo A. Gemelli, 8, Rome, RM 00168, Italy.
abbatea{at}yahoo.com
OBJECTIVES: The purpose of this study was to evaluate a potential correlation between apoptotic rate (AR), post-infarction left ventricular (LV) remodeling, and clinical characteristics in subjects who died late ( 10 days) after an acute myocardial infarction (AMI) with evidence of persistent occlusion of the infarct-related artery at autopsy.
BACKGROUND: Apoptosis contributes to myocardiocyte loss in cardiac disease and may have a pathophysiologic role in post-infarction LV remodeling.
METHODS: The AR was calculated at the site of infarction and in remote unaffected LV regions, using co-localization of in situ end labeling for deoxyribonucleic acid fragmentation and immunohistochemistry for caspase-3, in 14 subjects who died within two months after AMI. Correlation between AR and clinical characteristics such as age, site of AMI, transmural extension, multivessel coronary disease, and signs and/or symptoms of heart failure (HF), at the time of initial hospitalization for AMI or subsequently before death, was assessed using non-parametric statistical tests. Parameters of LV remodeling including diameters, free wall thickness, diameter-to-wall-thickness ratio, and mass were measured at gross examination at autopsy. Values are expressed as median (interquartile range).
RESULTS: Among clinical variables, early symptomatic post-infarction HF (9 cases, 64%) was associated with nearly fourfold increased AR at the site of infarction (26.2% [24.5% to 28.8%] vs. 6.4% [1.9% to 13.3%], p = 0.001). Moreover, AR both at the site of infarction and in unaffected regions was significantly correlated with parameters of progressive LV remodeling (p < 0.05).
CONCLUSIONS: Our data show that in patients dying 10 days after AMI, myocardial apoptosis is strongly associated with and may be a major determinant of unfavorable LV remodeling and early symptomatic post-infarction HF.
|
Abbreviations and Acronyms
| | AEC | | 3-amino-9-ethylcarbazide | | AMI | | acute myocardial infarction | | AR | | apoptotic rate | | DNA | | deoxyribonucleic acid | | HF | | heart failure | | IRA | | infarct-related artery | | LV | | left ventricle/ventricular | | PCNA | | proliferating cell nuclear antigen | | TUNEL | | terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling |
|
This article has been cited by other articles:
|
|
|
|
 
L. Ding, L. Dong, X. Chen, L. Zhang, X. Xu, A. Ferro, and B. Xu
Increased Expression of Integrin-Linked Kinase Attenuates Left Ventricular Remodeling and Improves Cardiac Function After Myocardial Infarction
Circulation,
September 1, 2009;
120(9):
764 - 773.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R J Hassink, H Nakajima, H O Nakajima, P A Doevendans, and L J Field
Expression of a transgene encoding mutant p193/CUL7 preserves cardiac function and limits infarct expansion after myocardial infarction
Heart,
July 15, 2009;
95(14):
1159 - 1164.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Niessner, P. J. Hohensinner, K. Rychli, S. Neuhold, G. Zorn, B. Richter, M. Hulsmann, R. Berger, D. Mortl, K. Huber, et al.
Prognostic value of apoptosis markers in advanced heart failure patients
Eur. Heart J.,
April 1, 2009;
30(7):
789 - 796.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Xiao, Q. She, Y. Wang, K. Luo, Y. Yin, R. Hu, and K. Huang
Effect of allopurinol on cardiomyocyte apoptosis in rats after myocardial infarction
Eur J Heart Fail,
January 1, 2009;
11(1):
20 - 27.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Crea, P. G. Camici, R. De Caterina, and G. A. Lanza
CHAPTER 17 Chronic Ischaemic Heart Disease
ESC Textbook of Cardiovascular Medicine,
January 1, 2009;
2(1):
med-9780199566990-chapter - med-9780199566990-chapter.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Abbate, F. N. Salloum, E. Vecile, A. Das, N. N. Hoke, S. Straino, G. G.L. Biondi-Zoccai, J.-E. Houser, I. Z. Qureshi, E. D. Ownby, et al.
Anakinra, a Recombinant Human Interleukin-1 Receptor Antagonist, Inhibits Apoptosis in Experimental Acute Myocardial Infarction
Circulation,
May 20, 2008;
117(20):
2670 - 2683.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. K. Yankey, T. Li, A. Kilic, G. Cheng, A. Satpute, K. Savai, S. Li, S. L. Moainie, D. Prastein, C. DeFillipi, et al.
Regional remodeling strain and its association with myocardial apoptosis after myocardial infarction in an ovine model.
J. Thorac. Cardiovasc. Surg.,
May 1, 2008;
135(5):
991 - 998.e2.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. N. Salloum, A. Abbate, A. Das, J.-E. Houser, C. A. Mudrick, I. Z. Qureshi, N. N. Hoke, S. K. Roy, W. R. Brown, S. Prabhakar, et al.
Sildenafil (Viagra) attenuates ischemic cardiomyopathy and improves left ventricular function in mice
Am J Physiol Heart Circ Physiol,
March 1, 2008;
294(3):
H1398 - H1406.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Lygate
Letter to the editor: Infarct size measurements are critically important when comparing interventions affecting ventricular remodeling
Am J Physiol Heart Circ Physiol,
November 1, 2007;
293(5):
H3221 - H3221.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Ibe, A. Saraste, S. Lindemann, S. Bruder, M. Buerke, H. Darius, K. Pulkki, and L.-M. Voipio-Pulkki
Cardiomyocyte apoptosis is related to left ventricular dysfunction and remodelling in dilated cardiomyopathy, but is not affected by growth hormone treatment
Eur J Heart Fail,
February 1, 2007;
9(2):
160 - 167.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Xydas, A. R. Kherani, J. S. Chang, S. Klotz, I. Hay, C. J. Mutrie, G. W. Moss, A. Gu, A. R. Schulman, D. Gao, et al.
beta2-Adrenergic Stimulation Attenuates Left Ventricular Remodeling, Decreases Apoptosis, and Improves Calcium Homeostasis in a Rodent Model of Ischemic Cardiomyopathy
J. Pharmacol. Exp. Ther.,
May 1, 2006;
317(2):
553 - 561.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L Galiuto, M Lotrionte, F Crea, A Anselmi, G G L Biondi-Zoccai, F De Giorgio, A Baldi, F Baldi, G Possati, M Gaudino, et al.
Impaired coronary and myocardial flow in severe aortic stenosis is associated with increased apoptosis: a transthoracic Doppler and myocardial contrast echocardiography study
Heart,
February 1, 2006;
92(2):
208 - 212.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Abbate, R. Bussani, G. G.L. Biondi-Zoccai, D. Santini, A. Petrolini, F. D. Giorgio, F. Vasaturo, S. Scarpa, A. Severino, G. Liuzzo, et al.
Infarct-related artery occlusion, tissue markers of ischaemia, and increased apoptosis in the peri-infarct viable myocardium
Eur. Heart J.,
October 1, 2005;
26(19):
2039 - 2045.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Suzuki, T. J. Moraes, E. Vachon, H. H. Ginzberg, T.-T. Huang, M. A. Matthay, M. D. Hollenberg, J. Marshall, C. A. G. McCulloch, M. T. H. Abreu, et al.
Proteinase-Activated Receptor-1 Mediates Elastase-Induced Apoptosis of Human Lung Epithelial Cells
Am. J. Respir. Cell Mol. Biol.,
September 1, 2005;
33(3):
231 - 247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Schaper and A. Elsasser
Reply
J. Am. Coll. Cardiol.,
February 1, 2005;
45(3):
466 - 467.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D Santini, A Abbate, S Scarpa, F Vasaturo, G G Biondi-Zoccai, R Bussani, F De Giorgio, F Bassan, D Camilot, M P Di Marino, et al.
Surviving acute myocardial infarction: survivin expression in viable cardiomyocytes after infarction
J. Clin. Pathol.,
December 1, 2004;
57(12):
1321 - 1324.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. D. Patten, I. Pourati, M. J. Aronovitz, J. Baur, F. Celestin, X. Chen, A. Michael, S. Haq, S. Nuedling, C. Grohe, et al.
17{beta}-Estradiol Reduces Cardiomyocyte Apoptosis In Vivo and In Vitro via Activation of Phospho-Inositide-3 Kinase/Akt Signaling
Circ. Res.,
October 1, 2004;
95(7):
692 - 699.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Mayorga, N. Bahi, M. Ballester, J. X. Comella, and D. Sanchis
Bcl-2 Is a Key Factor for Cardiac Fibroblast Resistance to Programmed Cell Death
J. Biol. Chem.,
August 13, 2004;
279(33):
34882 - 34889.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. I. Larsen and K. Dickstein
BNP in acute coronary syndromes: the heart expresses its suffering
Eur. Heart J.,
August 1, 2004;
25(15):
1284 - 1286.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A Abbate, D Santini, G G L Biondi-Zoccai, S Scarpa, F Vasaturo, G Liuzzo, R Bussani, F Silvestri, F Baldi, F Crea, et al.
Cyclo-oxygenase-2 (COX-2) expression at the site of recent myocardial infarction: friend or foe?
Heart,
April 1, 2004;
90(4):
440 - 443.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Velazquez and M. A. Pfeffer
Acute Heart Failure Complicating Acute Coronary Syndromes: A Deadly Intersection
Circulation,
February 3, 2004;
109(4):
440 - 442.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. N. DeMaria, O. Ben-Yehuda, D. Berman, G. K. Feld, B. H. Greenberg, J. D. Knoke, K. U. Knowlton, W. Y. W. Lew, and S. Tsimikas
Highlights of the year in JACC 2003
J. Am. Coll. Cardiol.,
December 17, 2003;
42(12):
2156 - 2166.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. A. Webster and N. H. Bishopric
Apoptosis Inhibitors for Heart Disease
Circulation,
December 16, 2003;
108(24):
2954 - 2956.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R Bussani, A Abbate, G G L Biondi-Zoccai, A Dobrina, A M Leone, D Camilot, M P Di Marino, F Baldi, F Silvestri, L M Biasucci, et al.
Right ventricular dilatation after left ventricular acute myocardial infarction is predictive of extremely high peri-infarctual apoptosis at postmortem examination in humans
J. Clin. Pathol.,
September 1, 2003;
56(9):
672 - 676.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
