CLINICAL STUDIES
Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death
Jamshid Shirani, MD, FACC*,
Ruth Pick, MD ,
William C. Roberts, MD, FACC and
Barry J. Maron, MD, FACC
* Departments of Medicine (Division of Cardiology) and Pathology, Albert Einstein College of Medicine, Bronx, New York, USA
Cardiac Morphology Laboratory, Michael Reese Hospital and Medical Center, Chicago, Illinois, USA
Baylor Cardiovascular Institute, Baylor University Medical Center, Dallas, Texas, USA
Minneapolis Heart Institute Foundation, Minneapolis, Minnesota, USA
Manuscript received December 18, 1997;
revised manuscript received July 8, 1999,
accepted September 10, 1999.
Reprint requests and correspondence: Dr. Jamshid Shirani, The Jack D. Weiler Hospital of the Albert Einstein College of Medicine, 1825 Eastchester Road, Room W1-70K, Bronx, New York 10461
jshirani{at}montefiore.org
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is a primary cardiac disease with a diverse clinical spectrum, in which many of the abnormal structural and pathophysiologic features are consequences of inappropriate left ventricular hypertrophy.
METHODS
We analyzed the amount, distribution and structure of the cardiac collagen network in transmural sections of the ventricular septum (thickness 17 to 40 mm, mean 25 mm) in 16 previously asymptomatic children and young adults with HCM (11 to 31 years of age, mean 20 years) who died suddenly. The morphologic appearance and volume fractions of interstitial (matrix) and perivascular (adventitial) collagen were analyzed with polarization microscopy and computerized videodensitometry in picrosirius red-stained sections. Findings were compared with 16 structurally normal hearts, 5 with systemic hypertension and 6 infants who died of HCM.
RESULTS
Adults and young children with HCM had an eightfold greater amount of matrix collagen compared with normal controls (14.1 ± 8.8% vs. 1.8 ± 1% of the tissue section; p < 0.0001), and a threefold increase compared with patients with systemic hypertension (4.5 ± 1.3%; p < 0.001) and infants with HCM (4.0 ± 2.4%; p < 0.001). Compared with normal controls and hypertensives, adults and young children (and infants) with HCM showed increased numbers and thickness of each collagen fiber component of the matrix (perimysial coils, pericellular weaves and struts), which were often arranged in disorganized patterns. In HCM patients, the amount of collagen was not a consequence of other clinical, demographic and morphologic disease variables.
CONCLUSIONS
Left ventricular collagen matrix in young, previously asymptomatic patients with HCM who died suddenly is morphologically abnormal and substantially increased in size. The enlarged matrix collagen compartment is present in HCM at an early age, further expands during growth, is partially responsible for increased ventricular septal thickness and likely represents a primary morphologic abnormality in this disease. These findings support the view that the complex HCM disease process is not confined to sarcomere protein abnormalities, but also involves connective tissue elements.
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Abbreviations and Acronyms
| | HCM | = hypertrophic cardiomyopathy | | LV | = left ventricle (ventricular) |
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|
|
|
|
|
|
|
F. Cambronero, F. Marin, V. Roldan, D. Hernandez-Romero, M. Valdes, and G. Y.H. Lip
Biomarkers of pathophysiology in hypertrophic cardiomyopathy: implications for clinical management and prognosis
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(2009)
ehn538v1.
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|
|
|
|
|
|
|
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[PDF]
|
|
|
|
|
|
|
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1(3):
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|
|
|
|
|
|
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49(7):
1090 - 1096.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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247(3):
788 - 796.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Adabag, B. J. Maron, E. Appelbaum, C. J. Harrigan, J. L. Buros, C. M. Gibson, J. R. Lesser, C. A. Hanna, J. E. Udelson, W. J. Manning, et al.
Occurrence and Frequency of Arrhythmias in Hypertrophic Cardiomyopathy in Relation to Delayed Enhancement on Cardiovascular Magnetic Resonance
J. Am. Coll. Cardiol.,
April 8, 2008;
51(14):
1369 - 1374.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Ganame, L. Mertens, B. W. Eidem, P. Claus, J. D'hooge, L. M. Havemann, C. J. McMahon, M. A. A. Elayda, W. K. Vaughn, J. A. Towbin, et al.
Regional myocardial deformation in children with hypertrophic cardiomyopathy: morphological and clinical correlations
Eur. Heart J.,
December 1, 2007;
28(23):
2886 - 2894.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
M. W. Hansen and N. Merchant
MRI of Hypertrophic Cardiomyopathy: Part I, MRI Appearances
Am. J. Roentgenol.,
December 1, 2007;
189(6):
1335 - 1343.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
C. J. McLeod, S. R. Ommen, M. J. Ackerman, P. L. Weivoda, W. K. Shen, J. A. Dearani, H. V. Schaff, A. J. Tajik, and B. J. Gersh
Surgical septal myectomy decreases the risk for appropriate implantable cardioverter defibrillator discharge in obstructive hypertrophic cardiomyopathy
Eur. Heart J.,
November 1, 2007;
28(21):
2583 - 2588.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
E. W. Daw, S. N. Chen, G. Czernuszewicz, R. Lombardi, Y. Lu, J. Ma, R. Roberts, S. Shete, and A. J. Marian
Genome-wide mapping of modifier chromosomal loci for human hypertrophic cardiomyopathy
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16(20):
2463 - 2471.
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|
|
|
|
|
|
|
T. Germans, A. A.M. Wilde, P. A. Dijkmans, W. Chai, O. Kamp, Y. M. Pinto, and A. C. van Rossum
Structural Abnormalities of the Inferoseptal Left Ventricular Wall Detected by Cardiac Magnetic Resonance Imaging in Carriers of Hypertrophic Cardiomyopathy Mutations
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48(12):
2518 - 2523.
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|
|
|
|
|
|
|
K. M. Harris, P. Spirito, M. S. Maron, A. G. Zenovich, F. Formisano, J. R. Lesser, S. Mackey-Bojack, W. J. Manning, J. E. Udelson, and B. J. Maron
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114(3):
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|
|
|
|
|
|
|
A. D'Andrea, P. Caso, S. Severino, S. Cuomo, G. Capozzi, P. Calabro, G. Cice, L. Ascione, M. Scherillo, and R. Calabro
Prognostic value of intra-left ventricular electromechanical asynchrony in patients with hypertrophic cardiomyopathy
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June 1, 2006;
27(11):
1311 - 1318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A D'Andrea, P Caso, S Cuomo, G Salerno, R Scarafile, C Mita, G De Corato, B Sarubbi, M Scherillo, R Calabro, et al.
Prognostic value of intra-left ventricular electromechanical asynchrony in patients with mild hypertrophic cardiomyopathy compared with power athletes * Commentary.
Br. J. Sports Med.,
March 1, 2006;
40(3):
244 - 250.
[Abstract]
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|
|
|
|
|
|
|
A. J. Marian, V. Senthil, S. N. Chen, and R. Lombardi
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J. Am. Coll. Cardiol.,
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47(4):
827 - 834.
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|
|
|
|
|
|
|
C. M. Wolf, I. P. G. Moskowitz, S. Arno, D. M. Branco, C. Semsarian, S. A. Bernstein, M. Peterson, M. Maida, G. E. Morley, G. Fishman, et al.
Somatic events modify hypertrophic cardiomyopathy pathology and link hypertrophy to arrhythmia
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December 13, 2005;
102(50):
18123 - 18128.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Isobe, H. Izawa, M. Iwase, M. Nanasato, M. Nonokawa, A. Ando, S. Ohshima, K. Nagata, K. Kato, T. Nishizawa, et al.
Cardiac 123I-MIBG Reflects Left Ventricular Functional Reserve in Patients with Nonobstructive Hypertrophic Cardiomyopathy
J. Nucl. Med.,
June 1, 2005;
46(6):
909 - 916.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Knaapen, W. G. van Dockum, O. Bondarenko, W. E.M. Kok, M. J.W. Gotte, R. Boellaard, A. M. Beek, C. A. Visser, A. C. van Rossum, A. A. Lammertsma, et al.
Delayed Contrast Enhancement and Perfusable Tissue Index in Hypertrophic Cardiomyopathy: Comparison Between Cardiac MRI and PET
J. Nucl. Med.,
June 1, 2005;
46(6):
923 - 929.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Lutucuta, N. Tsybouleva, M. Ishiyama, G. DeFreitas, L. Wei, B. Carabello, and A.J. Marian
Induction and reversal of cardiac phenotype of human hypertrophic cardiomyopathy mutation cardiac troponin T-Q92 in switch on-switch off bigenic mice
J. Am. Coll. Cardiol.,
December 7, 2004;
44(11):
2221 - 2230.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. C. Moon, E. Reed, M. N. Sheppard, A. G. Elkington, S. Ho, M. Burke, M. Petrou, and D. J. Pennell
The histologic basis of late gadolinium enhancement cardiovascular magnetic resonance in hypertrophic cardiomyopathy
J. Am. Coll. Cardiol.,
June 16, 2004;
43(12):
2260 - 2264.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Tsybouleva, L. Zhang, S. Chen, R. Patel, S. Lutucuta, S. Nemoto, G. DeFreitas, M. Entman, B. A. Carabello, R. Roberts, et al.
Aldosterone, Through Novel Signaling Proteins, Is a Fundamental Molecular Bridge Between the Genetic Defect and the Cardiac Phenotype of Hypertrophic Cardiomyopathy
Circulation,
March 16, 2004;
109(10):
1284 - 1291.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Maron, W. J. McKenna, G. K. Danielson, L. J. Kappenberger, H. J. Kuhn, C. E. Seidman, P. M. Shah, W. H. Spencer III, P. Spirito, F. J. Ten Cate, et al.
American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines
J. Am. Coll. Cardiol.,
November 5, 2003;
42(9):
1687 - 1713.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Writing Committee Members, B. J. Maron, W. J. McKenna, G. K. Danielson, L. J. Kappenberger, H. J. Kuhn, C. E. Seidman, P. M. Shah, W. H. Spencer III, P. Spirito, et al.
American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy: A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines
Eur. Heart J.,
November 1, 2003;
24(21):
1965 - 1991.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Lombardi, S. Betocchi, M. A. Losi, C. G. Tocchetti, M. Aversa, M. Miranda, G. D'Alessandro, A. Cacace;, Q. Ciampi, and M. Chiariello
Myocardial Collagen Turnover in Hypertrophic Cardiomyopathy
Circulation,
September 23, 2003;
108(12):
1455 - 1460.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.J. Marian and R. Roberts
To Screen or Not Is Not the Question-- It Is When and How to Screen
Circulation,
May 6, 2003;
107(17):
2171 - 2174.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Marian
On predictors of sudden cardiac death in hypertrophic cardiomyopathy
J. Am. Coll. Cardiol.,
March 19, 2003;
41(6):
994 - 996.
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Olivotto, R. Gistri, P. Petrone, E. Pedemonte, D. Vargiu, and F. Cecchi
Maximum left ventricular thickness and risk of sudden death in patients with hypertrophic cardiomyopathy
J. Am. Coll. Cardiol.,
January 15, 2003;
41(2):
315 - 321.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. J. Maron
Hypertrophic Cardiomyopathy: A Systematic Review
JAMA,
March 13, 2002;
287(10):
1308 - 1320.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kuhn, F. Gietzen, and C. Leuner
'The abrupt no-flow': a no-reflow like phenomenon in hypertrophic cardiomyopathy
Eur. Heart J.,
January 1, 2002;
23(1):
91 - 93.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Patel, S. F. Nagueh, N. Tsybouleva, M. Abdellatif, S. Lutucuta, H. A. Kopelen, M. A. Quinones, W. A. Zoghbi, M. L. Entman, R. Roberts, et al.
Simvastatin Induces Regression of Cardiac Hypertrophy and Fibrosis and Improves Cardiac Function in a Transgenic Rabbit Model of Human Hypertrophic Cardiomyopathy
Circulation,
July 17, 2001;
104(3):
317 - 324.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Shirani, J. Lee, R. Quigg, R. Pick, S. L. Bacharach, and V. Dilsizian
Relation of thallium uptake to morphologic features of chronic ischemic heart disease: evidence for myocardial remodeling in noninfarcted myocardium
J. Am. Coll. Cardiol.,
July 1, 2001;
38(1):
84 - 90.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D.-S. Lim, S. Lutucuta, P. Bachireddy, K. Youker, A. Evans, M. Entman, R. Roberts, and A. J. Marian
Angiotensin II Blockade Reverses Myocardial Fibrosis in a Transgenic Mouse Model of Human Hypertrophic Cardiomyopathy
Circulation,
February 13, 2001;
103(6):
789 - 791.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Y. Li, Y. Q. Feng, T. Kadokami, C. F. McTiernan, R. Draviam, S. C. Watkins, and A. M. Feldman
Myocardial extracellular matrix remodeling in transgenic mice overexpressing tumor necrosis factor alpha can be modulated by anti-tumor necrosis factor alpha therapy
PNAS,
November 7, 2000;
97(23):
12746 - 12751.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
