Tissue doppler imaging consistently detects myocardial contraction and relaxation abnormalities, irrespective of cardiac hypertrophy, in a transgenic rabbit model of human hypertrophic cardiomyopathy

Sherif F. Nagueh, Helen A. Kopelen, Do-Sun Lim, William A. Zoghbi, Miguel A. Quiñones, Robert Roberts, Ali J. Marian

Research output: Contribution to journalArticle

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Abstract

Background - Hypertrophic cardiomyopathy (HCM) is diagnosed clinically by the presence of left ventricular hypertrophy (LVH). However, LVH is absent in a significant number of genotype-positive patients. Because myocyte dysfunction and disarray are the primary abnormalities in HCM, we reasoned that tissue Doppler imaging could identify contraction and relaxation abnormalities, irrespective of hypertrophy, in a transgenic rabbit model of human HCM. Methods and Results - M-mode, 2D, Doppler echocardiography and tissue Doppler imaging were performed in nontransgenic (n=24), wild-type β-myosin heavy chain-arginine403 (n=14), and mutant β-myosin heavy chain-glutamic acid403 (n=24) transgenic rabbits. Mean septal thicknesses were 2.0±0.3, 2.0±0.25, and 2.75±0.3 mm in the 3 groups, respectively (P=0.001). LVH was absent in 9 of the 24 mutant rabbits. Left ventricular dimensions, systolic function, heart rate, mitral inflow velocities, and time intervals were similar in the groups. However, the difference between atrial reversal and transmitral A wave duration was increased in the mutant rabbits (P<0.001). More importantly, systolic and early diastolic tissue Doppler velocities were significantly lower in all mutant rabbits (7.45±2.2 versus 10.8±2.3 cm/s in nontransgenic and 9.0±0.76 cm/s in wild-type; P<0.001), including the 9 without LVH. A systolic velocity <8.5 cm/s had an 86% sensitivity and 100% specificity in identifying the mutant transgenic rabbits. Conclusions - Myocardial contraction and relaxation were reduced in the mutant β-myosin heavy chain-glutamic acid403 transgenic rabbit model of human HCM, irrespective of the presence or absence of LVH. In addition, tissue Doppler imaging is more sensitive than conventional echocardiography for HCM screening.

Original languageEnglish
Pages (from-to)1346-1350
Number of pages5
JournalCirculation
Volume102
Issue number12
Publication statusPublished - 2000 Sep 19
Externally publishedYes

Fingerprint

Myocardial Contraction
Hypertrophic Cardiomyopathy
Cardiomegaly
Left Ventricular Hypertrophy
Rabbits
Myosin Heavy Chains
Doppler Echocardiography
Muscle Cells
Hypertrophy
Echocardiography
Heart Rate
Genotype
Sensitivity and Specificity

Keywords

  • Cardiomyopathy
  • Echocardiography
  • Genetics
  • Hypertrophy
  • Imaging

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Tissue doppler imaging consistently detects myocardial contraction and relaxation abnormalities, irrespective of cardiac hypertrophy, in a transgenic rabbit model of human hypertrophic cardiomyopathy. / Nagueh, Sherif F.; Kopelen, Helen A.; Lim, Do-Sun; Zoghbi, William A.; Quiñones, Miguel A.; Roberts, Robert; Marian, Ali J.

In: Circulation, Vol. 102, No. 12, 19.09.2000, p. 1346-1350.

Research output: Contribution to journalArticle

Nagueh, Sherif F. ; Kopelen, Helen A. ; Lim, Do-Sun ; Zoghbi, William A. ; Quiñones, Miguel A. ; Roberts, Robert ; Marian, Ali J. / Tissue doppler imaging consistently detects myocardial contraction and relaxation abnormalities, irrespective of cardiac hypertrophy, in a transgenic rabbit model of human hypertrophic cardiomyopathy. In: Circulation. 2000 ; Vol. 102, No. 12. pp. 1346-1350.
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T1 - Tissue doppler imaging consistently detects myocardial contraction and relaxation abnormalities, irrespective of cardiac hypertrophy, in a transgenic rabbit model of human hypertrophic cardiomyopathy

AU - Nagueh, Sherif F.

AU - Kopelen, Helen A.

AU - Lim, Do-Sun

AU - Zoghbi, William A.

AU - Quiñones, Miguel A.

AU - Roberts, Robert

AU - Marian, Ali J.

PY - 2000/9/19

Y1 - 2000/9/19

N2 - Background - Hypertrophic cardiomyopathy (HCM) is diagnosed clinically by the presence of left ventricular hypertrophy (LVH). However, LVH is absent in a significant number of genotype-positive patients. Because myocyte dysfunction and disarray are the primary abnormalities in HCM, we reasoned that tissue Doppler imaging could identify contraction and relaxation abnormalities, irrespective of hypertrophy, in a transgenic rabbit model of human HCM. Methods and Results - M-mode, 2D, Doppler echocardiography and tissue Doppler imaging were performed in nontransgenic (n=24), wild-type β-myosin heavy chain-arginine403 (n=14), and mutant β-myosin heavy chain-glutamic acid403 (n=24) transgenic rabbits. Mean septal thicknesses were 2.0±0.3, 2.0±0.25, and 2.75±0.3 mm in the 3 groups, respectively (P=0.001). LVH was absent in 9 of the 24 mutant rabbits. Left ventricular dimensions, systolic function, heart rate, mitral inflow velocities, and time intervals were similar in the groups. However, the difference between atrial reversal and transmitral A wave duration was increased in the mutant rabbits (P<0.001). More importantly, systolic and early diastolic tissue Doppler velocities were significantly lower in all mutant rabbits (7.45±2.2 versus 10.8±2.3 cm/s in nontransgenic and 9.0±0.76 cm/s in wild-type; P<0.001), including the 9 without LVH. A systolic velocity <8.5 cm/s had an 86% sensitivity and 100% specificity in identifying the mutant transgenic rabbits. Conclusions - Myocardial contraction and relaxation were reduced in the mutant β-myosin heavy chain-glutamic acid403 transgenic rabbit model of human HCM, irrespective of the presence or absence of LVH. In addition, tissue Doppler imaging is more sensitive than conventional echocardiography for HCM screening.

AB - Background - Hypertrophic cardiomyopathy (HCM) is diagnosed clinically by the presence of left ventricular hypertrophy (LVH). However, LVH is absent in a significant number of genotype-positive patients. Because myocyte dysfunction and disarray are the primary abnormalities in HCM, we reasoned that tissue Doppler imaging could identify contraction and relaxation abnormalities, irrespective of hypertrophy, in a transgenic rabbit model of human HCM. Methods and Results - M-mode, 2D, Doppler echocardiography and tissue Doppler imaging were performed in nontransgenic (n=24), wild-type β-myosin heavy chain-arginine403 (n=14), and mutant β-myosin heavy chain-glutamic acid403 (n=24) transgenic rabbits. Mean septal thicknesses were 2.0±0.3, 2.0±0.25, and 2.75±0.3 mm in the 3 groups, respectively (P=0.001). LVH was absent in 9 of the 24 mutant rabbits. Left ventricular dimensions, systolic function, heart rate, mitral inflow velocities, and time intervals were similar in the groups. However, the difference between atrial reversal and transmitral A wave duration was increased in the mutant rabbits (P<0.001). More importantly, systolic and early diastolic tissue Doppler velocities were significantly lower in all mutant rabbits (7.45±2.2 versus 10.8±2.3 cm/s in nontransgenic and 9.0±0.76 cm/s in wild-type; P<0.001), including the 9 without LVH. A systolic velocity <8.5 cm/s had an 86% sensitivity and 100% specificity in identifying the mutant transgenic rabbits. Conclusions - Myocardial contraction and relaxation were reduced in the mutant β-myosin heavy chain-glutamic acid403 transgenic rabbit model of human HCM, irrespective of the presence or absence of LVH. In addition, tissue Doppler imaging is more sensitive than conventional echocardiography for HCM screening.

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KW - Echocardiography

KW - Genetics

KW - Hypertrophy

KW - Imaging

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