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(Circulation. 2000;102:1276.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Echocardiographic Characterization of Cardiomyopathy in Friedreich’s Ataxia With Tissue Doppler Echocardiographically Derived Myocardial Velocity Gradients
aw Palka, MDFrom the National Heart and Lung Institute (D.P.D., J.E.D., P.P., A.L., P.N.) and Division of Medicine (D.J.R.N.), Imperial College School of Science, Technology and Medicine, London, UK.
Correspondence to David P. Dutka, DM, National Heart and Lung Institute, Imperial College School of Science, Technology and Medicine, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK. E-mail d.dutka{at}ic.ac.uk
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Abstract |
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Background—Conventional and tissue Doppler echocardiographically derived myocardial velocity gradients (MVGs) were used to characterize the myocardium in patients with Friedreich’s ataxia (FRDA), and the relationship between MVGs and the mutation in the FRDA gene, a GAA triplet repeat expansion, was investigated.
Methods and Results—We studied 29 patients with FRDA (10 men, mean age 31±9 years) who were homozygous for the GAA expansion in the FRDA gene and were without cardiac symptoms. A comparison was made with a group of 30 age-matched control subjects. In patients with FRDA, interventricular septal thickness (1.17±0.26 versus 0.85±0.13 cm, P<0.005), posterior left ventricular wall thickness (1.00±0.24 versus 0.88±0.15 cm, P<0.01), and left atrial diameter (3.3±0.5 versus 2.9±0.3 cm, P=0.01) were increased compared with control subjects. MVGs were reduced in FRDA during systole (3.1±1.2 versus 4.5±0.5 s-1, P<0.0001) and in early diastole (4.9±2.7 versus 8.8±1.8 s-1, P<0.0001) but increased in late diastole (2.0±1.3 versus 1.1±0.9 s-1, P<0.01). The strongest relationship was seen between age-corrected early diastolic MVGs and the GAA expansion in the smaller allele of the FRDA gene (r=-0.68, P<0.0001).
Conclusions—MVGs offer a means of further characterizing the myocardial abnormalities in patients with FRDA. Early diastolic MVGs appear to relate most closely to the genetic abnormality and the consequential reduction in frataxin protein.
Key Words: echocardiography • cardiomyopathy • imaging • myocardium
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Friedreich’s ataxia (FRDA) is an inherited neurodegenerative disorder associated with cardiomyopathy and impaired glucose tolerance.1 2 3 4 5 6 The changes in the left ventricle (LV) consist mainly of cellular hypertrophy, diffuse fibrosis, and focal myocardial necrosis.7 Our recent findings8 are in accord with other reports1 2 3 4 5 6 that the LV hypertrophy (concentric, asymmetrical, or both) and thickening of the papillary muscles are variable in FRDA. The most common echocardiographic abnormality is asymmetrical LV hypertrophy and thickening of the papillary muscles, although the range of abnormalities appears to be wide.8
The genetic basis for FRDA is a GAA trinucleotide repeat expansion in the first intron of gene X25,9 which encodes a 210–amino acid protein, frataxin. In FRDA, it is postulated that the GAA expansion leads to reduced levels of frataxin, resulting in abnormalities of mitochondrial iron transport and antioxidant systems.10 11 12
We used conventional echocardiography and tissue Doppler echocardiography13 14 15 16 to further characterize the myocardial abnormalities associated with FRDA. Tissue Doppler echocardiography facilitates quantification of intramural transmyocardial velocities, and the myocardial velocity gradient (MVG) offers an assessment of structural and functional changes over the cardiac cycle.17 18 19 MVG is independent of cardiac motion20 21 and less affected by alterations in preload than Doppler transmitral velocities.22 In addition, MVG in early diastole, particularly when corrected for age, may differentiate between physiological and pathological ventricular hypertrophy.21 The aims of the present study were to define cardiac morphology with conventional echocardiography and to use tissue Doppler echocardiographically derived MVGs to investigate the relationship between cardiac phenotype and genotype in FRDA.
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Twenty-nine subjects with FRDA, who were homozygous for the GAA expansion in the FRDA gene, were studied and compared with 30 age-matched healthy subjects. The diagnosis was confirmed by the presence of GAA expansions in both alleles of the FRDA gene. The clinical characteristics of the patients and control subjects are given in Table 1
. All were in sinus
rhythm, and in the patients with FRDA, clinical examination of the
heart was normal except for 3 patients who had a soft
pansystolic murmur at the apex.
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In the patients, the mean±SD age of onset of ataxic symptoms was 11±5 years (range 5 to 28 years), with a mean duration of neurological symptoms of 16±8 years at the time of the study. Seventeen (59%) patients were dependent on others for the activities of daily living. None of the patients or control subjects were receiving any cardiac medication, and the study was approved by the hospital ethical committee.
Analysis of the GAA Expansion
The size of the GAA triplet repeat was determined with
long-range polymerase chain reaction (PCR) techniques with genomic DNA
extracted from peripheral blood leukocytes. The amplimers
5'-GGGATTGGTTGCCAGTGCTTAAAAGTTAG-3' and
5'-GATCTAAGGACCATCATCATGGCCACACTTGCC-3' were used to generate a
product of 457 bp plus the number of base pairs that composed the
GAA triplet repeat expansion. The ELONGASE enzyme mix (Taq
and Pyrococcus species polymerases; GIBCO BRL) was used for
amplification (35 cycles; 94°C for 30 seconds, 60°C for 30 seconds,
and 68°C for 120 seconds). The PCR products were separated by
electrophoresis through a 1% agarose gel, and the size of the
expansion was determined by ethidium bromide staining. The results were
confirmed with the Expand high-fidelity PCR system (Taq and
Pwo polymerases; Boehringer-Mannheim) with 10 cycles
of 94°C for 15 seconds, 60°C for 30 seconds, and 68°C for 120
seconds, followed by 25 cycles in which the 68°C step was lengthened
by 20 s/cycle. The PCR products were transferred to Hybond
N+, and the size of the GAA expansion was
confirmed by hybridization with 100 ng of a
(GAA)10 oligonucleotide
end-labeled with [
-32P]ATP (5000 Ci/mmol;
Amersham).
Echocardiography
The echocardiographic studies (conventional and
tissue Doppler echocardiography) were
recorded with a modified Acuson 128 XP10 scanner. M-mode,
2-dimensional, and Doppler blood flow studies were recorded in
a conventional manner. Measurements were made from the M-mode
recordings according to the standards of the American Society
of Echocardiography,23 and
analysis was performed with the scanner software. LV dimensions
were measured from M-mode recordings at the level of the tips
of the mitral valve leaflets with the parasternal long-axis view.
Doppler blood flow studies and transmitral velocity waveforms were
recorded from the interrogating sample volume placed in the LV at
the tips of the mitral valve leaflets.24 Peak E- and
A-wave velocities, E/A ratio, E deceleration time, and isovolumic
relaxation time (IVRT) were recorded, and measurements were
averaged over 3 cardiac cycles.
Tissue Doppler Echocardiography
The scanner was modified as previously described for tissue
Doppler echocardiography by using low-velocity
ranges (0.2 to 24 cm/s).19 25 The Doppler information
was sampled from the myocardium of the posterior wall of
the LV with persistence off to eliminate movement blurring, and the
angle of the M-mode beam was aligned such that it was perpendicular to
the myocardium in the parasternal long-axis view. The image
was magnified to display the full thickness of the
myocardium throughout the cardiac cycle. Aliasing was
eliminated, and the gray-scale gain was adjusted to ensure delineation
of the epicardial and endocardial boundaries. The images were obtained
in freeze-frame mode, and the gray-scale and color images were stored
with the use of a dedicated system (TomTec). The MVGs were
analyzed from the tissue Doppler
echocardiography M-mode recordings as
previously described.18 19 The MVG was calculated as the
slope of the regression of myocardial velocities between the
endocardium and epicardium. Myocardial velocities were measured
automatically every 0.12 mm between endocardium and epicardium and
every 4 to 7 ms throughout each cardiac cycle depending on image
magnification and velocity scale. MVGs were expressed as a positive
value when the subendocardium was moving faster than the subepicardium
and negative when the subepicardium was moving faster than the
subendocardium.18 20 The peak MVG value was calculated in
systole, in early diastole (during rapid
ventricular filling), and in late diastole
(during atrial contraction) with the use of 3 cardiac cycles at the end
of held expiration, because MVG variability between cardiac cycles
increases markedly if respiration is not suspended.15 The
interobserver and intraobserver errors with this method of measuring
MVGs (mean±SD) are 0.1±0.2 and 0.2±0.2 s-1,
respectively.15
Tissue Doppler echocardiographically derived
indices are related to age, with early diastolic MVG
reduced by 
10% (2 s-1) for each decade
from the age of 20 years.19 26 Age-corrected MVGs were
calculated as previously described, with the formula: MVG measured in
early diastole+[(age-20)/10]*2).19 27
Statistical Methods
The results are expressed as mean±SD. The differences between
patients with FRDA and age-matched normal subjects were assessed by
unpaired Student’s t tests. The potential influence of
patient sex, age, heart rate, systolic and
diastolic blood pressures, and conventional
echocardiographic variables (including myocardial
wall thickness and transmitral Doppler blood inflow indices) on MVG
measurements were analyzed with stepwise
multivariate regression analysis. Finally,
simple linear regression was performed to investigate the relationship
between the size of the GAA expansion and cardiac phenotype.
The significance level, 
, was set at 0.05.
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Conventional Echocardiography
The echocardiographic data from the patients with FRDA and age-matched normal volunteers are presented in Table 2
. The interventricular
septum and the posterior LV wall were thicker in the patients with FRDA
than in the control subjects (38% and 14%, respectively; Table
2). The ventricular hypertrophy was
predominantly asymmetrical, with the septal thickness exceeding the
control mean+2 SDs in 45% of patients with FRDA. The LV cavity
was smaller and the left atrial diameter was larger in patients with
FRDA than in control subjects. There were no significant differences
between patients with FRDA and age-matched control subjects in LV mass
and ejection fraction.
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Transmitral Doppler blood flow indices demonstrated that only the E/A ratio was reduced (by -21%, P<0.005) in patients with FRDA; all other LV Doppler inflow indices, including E-wave deceleration time and IVRT, were similar to control values.
MVG Measurements
MVG measurements were different in all analyzed phases of
the cardiac cycle in patients with FRDA compared with age-matched
normal subjects (Figures 1 and 2). In systole and early
diastole (during rapid ventricular filling),
MVGs were reduced in patients with FRDA (systole 3.1±1.2 versus
4.6±0.5 s-1, P<0.0001; early
diastole 4.9±2.7 versus 8.8±1.7
s-1, P<0.0001). In contrast, in late
diastole during atrial contraction, the MVG was higher in
patients with FRDA than in control subjects (2.0±1.3 versus 1.2±0.9
s-1, P<0.01, Figure 1).
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Multivariate Analysis of MVGs
MVG measurements taken in diastole during rapid
ventricular filling and atrial contraction were age related
in both patients with FRDA and normal subjects but otherwise were
independent of other clinical and echocardiographic
variables, including heart rate, LV wall thickness, and transmitral
Doppler blood inflow indices.
Because tissue Doppler echocardiographically
derived indices are age related,19 26 the relationship
between the thickness of the LV posterior wall and age-corrected MVGs
in early diastole is presented in Figure 3. In 21 (72%) of the patients with
FRDA, early diastolic MVG was <8.8
s-11 (control mean-2 SD) in the absence
of hypertrophy of the LV posterior wall (<1.25 cm).
However, in 8 (28%) of the patients with FRDA, early
diastolic MVGs were within normal values. In comparison
with the other 21 subjects with FRDA, these 8 subjects had a smaller
GAA triplet repeat expansion (467±153 versus 760±225;
P<0.001) and less myocardial hypertrophy
(interventricular septal thickness 0.99±0.08 versus
1.25±0.27 cm; P<0.001) and tended to be older (35±9
versus 29±8 years; P=0.155). Other clinical and
echocardiographic measurements, including LV posterior
wall thickness, LV size, and transmitral Doppler blood inflow
indices, were similar in the 2 subgroups. In patients with FRDA, an
age-corrected early diastolic MVG of <8.8
s-1 was consistently present when
the size of the GAA expansion in the smaller allele of the FRDA
gene was >600 repeats.
|
) and age-matched control subjects (•). Lines indicate mean+2 SDs
of control subjects.
Relationship Between Genotype and
Echocardiographic Phenotype in FRDA
Echocardiography
A relationship was demonstrated between the number of GAA triplet
repeats in the smaller frataxin allele and diastolic
interventricular septal thickness (r=0.55,
P<0.005, Figure 4A), but the
relationship between the frataxin mutation and the thickness of the
posterior LV wall was weaker and of borderline significance
(r=0.35, P=0.06, Figure 4B). A
relationship was not found between the GAA triplet repeat expansion and
other conventional echocardiographic variables,
such as LV dimension, left atrial size, or transmitral Doppler
blood flow indices.
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MVG Measurements
Age-corrected MVGs were inversely related to the size of the
GAA triplet repeat expansion in all phases of the cardiac cycle.
Although MVG measurements correlated with the number of GAA repeats in
systole (r=-0.48, P<0.01, Figure 5A), early diastole
(r=-0.60, P<0.005, Figure 5B), and late
diastole (r=-0.48, P<0.01, Figure
5C), the strongest relationship was found for MVG measurements
corrected for age in early diastole (r=-0.68,
P<0.0005, Figure 5D).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The present study demonstrated that MVGs in systole and during the rapid ventricular filling phase of early diastole are reduced in patients with FRDA who are without cardiac symptoms. Tissue Doppler echocardiography may be useful to further our understanding of the changes in myocardial structure and function in inherited cardiomyopathies.
The precise molecular abnormalities that result in the development of cardiomyopathy in FRDA remain unclear. Retrospective studies have reported a relationship between the number of GAA repeats in the smaller frataxin allele and cardiomyopathy in approximately two thirds of patients homozygous for the GAA expansion.28 29 This is in accord with our experience, in which 46% of subjects homozygous for the GAA expansion had septal hypertrophy but the posterior wall was thickened in only 18%.8 In this prospective study, we confirmed the previous retrospective observation of a relationship between myocardial hypertrophy and the size of the GAA expansion in the FRDA gene30 but also demonstrated that MVG is abnormal in the majority of patients with FRDA. Although the 2-dimensional echocardiographic studies confirmed myocardial hypertrophy in approximately half of the subjects with FRDA, indices of LV systolic and diastolic function were within the normal range.
We used conventional echocardiography and tissue Doppler echocardiography to further characterize the myocardial abnormalities associated with FRDA. Tissue Doppler echocardiography is a recently introduced technique that enables abnormalities of cardiac structure and function to be characterized by using color Doppler information.17 18 19 20 31 32 The detection of consecutive phase shifts of the Doppler signal returning from the endocardium and epicardium, throughout the cardiac cycle, renders this technique particularly suited to the study of myocardial disease. A further advantage of this technique is the accurate definition of the endocardial boundary.25 MVG is also subject to less error than conventional echocardiography with respect to translational and rotational motion of the heart,20 changes in loading,22 and the degree of LV hypertrophy.21 Overall, the assessment of myocardial structure and function with this technique offers several potential benefits over conventional echocardiography.13 14 15 20 25
In patients with FRDA, systolic and early diastolic MVGs were reduced by 33% and 44%, respectively, compared with healthy control subjects. The inverse relationship between MVG and the number of GAA triplet repeats is presumed to reflect the reduction in frataxin in the myocyte.11 33 In 72% of patients with FRDA, early diastolic MVGs were reduced in excess of 2 SDs below the control mean in the absence of LV posterior wall hypertrophy. In the remaining subjects, early diastolic MVGs were within normal values. These findings confirm that the MVG is independent of myocardial hypertrophy, LV cavity size, and transmitral Doppler blood flow indices.
A number of factors influence cardiac diastolic function (eg, myocardial relaxation, elastic recoil, pericardial restraint, and atrial function), and myocardial abnormalities alter not only these factors but also their interrelationship. For example, in familial hypertrophic cardiomyopathy, the force of myocardial contraction starts to decline before the end of ventricular ejection, well in advance of mitral valve opening. Furthermore, myocardial diastolic function, as indicated by an increase in IVRT, is a sensitive index of myocardial ischemia and occurs well before a decline in myocardial systolic contractility, symptoms, and ECG changes are observed.
In FRDA, it has been proposed that the GAA expansion results in a reduction in mitochondrial frataxin, with abnormal iron metabolism and accumulation of free radicals that result in mitochondrial dysfunction.11 12 FRDA shares a number of common features with mitochondrial respiratory chain deficiency (including ataxia, diabetes, and cardiomyopathy), and the localization of frataxin to mitochondria supports the hypothesis that mitochondrial dysfunction plays a central role in FRDA.10 Abnormal respiratory chain complex I, II, and III activity ratios have been observed in the myocardium of FRDA subjects without evidence of derangement of the mitochondrial genome.11 The yeast counterpart of the FRDA protein is active in iron homeostasis, and disruption of the gene results in mitochondrial iron accumulation.12 It is proposed that the reduction in frataxin results in the activation of a mitochondrial iron transport system; a deficiency of a Krebs’ cycle enzyme, aconitase; and altered mitochondrial respiratory function through the iron-catalyzed Fenton reaction and oxidative stress.
Oxidative stress also plays a role in coronary artery disease, where ischemia promotes free radical formation, resulting in myocardial and endothelial injury with inactivation of nitric oxide, peroxidation, and altered membrane permeability.34 The potential protective role of vitamin E as an antioxidant is highlighted by the finding that familial isolated vitamin E deficiency is an autosomal recessive disorder that closely mimics FRDA such that the conditions are indistinguishable before genetic studies and plasma vitamin E measurement.35 In this study, the results of echocardiography were not reported, but unspecified slight and moderate electrocardiographic abnormalities were present in 4 of the 8 individuals studied, with another who experienced sudden death.
We propose that the abnormal MVG reflects the decreased myocardial contractility and relaxation secondary to abnormal mitochondrial function resulting from reduced levels of frataxin in FRDA. It remains unclear why some patients with profound neurological deficit have no or little evidence of cardiac abnormalities (including normal MVGs), whereas others have both reduced MVG and myocardial hypertrophy and much less neurological disability, although the antioxidant capacity of different organs varies.
Study Limitations
The effect of severe ataxia and wheelchair dependence on
echocardiographic measurements, including MVG, is
unknown. The absence of a relationship between the degree of
neurological deficit and MVG suggests that immobility does not
influence MVG any more than athleticism.21 Similarly, the
effect on the heart of the considerable effort of maintaining
independence despite severe ataxia and the effect of neurodegeneration
on cardiac innervation in FRDA remains unknown.
In Doppler echocardiography, "noise" may be observed at the top of the image in the near field, but this does not influence MVG measurements of the posterior wall of the LV, located in the lower third of the image. Furthermore, tissue Doppler echocardiography in the present study was limited to a section of the posterior wall of the LV because the angle dependence of Doppler information restricts accurate measurement of MVG to this region of the LV. We assumed that the abnormalities in this relatively small area of myocardium are representative of those in the entire LV.
Conclusions
The cardiomyopathy of FRDA is associated with
asymmetrical LV hypertrophy, a decrease in LV cavity size,
and a reduction in both systolic and early
diastolic MVGs. The strongest relationship was found
between the size of the smaller GAA triplet repeat expansion and early
diastolic MVG and interventricular septal
thickness. Tissue Doppler echocardiographically
derived MVG technique offers an additional means of assessing
structural and functional changes in inherited myocardial disease. The
role of this new echocardiographic technique to assess
myocardial dysfunction secondary to oxidative stress merits further
study.
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Acknowledgments |
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This work was supported in part by a British Heart Foundation grant (Drs Dutka and Nunez) and by the Special Trustees of the Hammersmith Hospital. We are grateful to Acuson (UK) Ltd for the loan evaluation of the echocardiographic equipment used in this study. We thank Drs Alan Fleming and Susan Chamberlain for helpful discussions.
Received January 19, 1999; revision received April 6, 2000; accepted April 13, 2000.
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References |
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|---|
1. Child JS, Perloff JK, Bach PM, et al. Cardiac involvement in Friedreich’s ataxia: a clinical study of 75 patients. J Am Coll Cardiol. 1986;7:1370–1378.[Abstract]
2. Giunta A, Maione S, Biagini R, et al. Noninvasive assessment of systolic and diastolic function in 50 patients with Friedreich’s ataxia. Cardiology. 1988;75:321–327.[Medline] [Order article via Infotrieve]
3. Unverferth DV, Schmidt WR, Baker PB, et al. Morphologic and functional characteristics of the heart in Friedreich’s ataxia. Am J Med. 1987;82:5–10.[Medline] [Order article via Infotrieve]
4.
Ackroyd RS, Finnegan JA, Green SH. Friedreich’s
ataxia: a clinical review with neurophysiological
and echocardiographic findings. Arch Dis
Child. 1984;59:217–221.
5.
Sutton MG, Olukotun AY, Tajik AJ, et al. Left
ventricular function in Friedreich’s ataxia: an
echocardiographic study. Br Heart J. 1980;44:309–316.
6.
Morvan D, Komajda M, Doan LD, et al.
Cardiomyopathy in Friedreich’s ataxia: a
Doppler-echocardiographic study. Eur
Heart J. 1992;13:1393–1398.
7.
Hewer RL. The heart in Friedreich’s ataxia. Br
Heart J. 1969;31:5–14.
8.
Dutka DP, Donnelly JE, Nihoyannopoulos P, et al.
Marked variation in the cardiomyopathy associated
with Friedreich’s ataxia. Heart. 1999;81:141–147.
9. Campuzano V, Montermini L, Molto MD, et al. Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science. 1996;271:1423–1427.[Abstract]
10. Koutnikova H, Campuzano V, Foury F, et al. Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin. Nat Genet. 1997;16:345–351.[Medline] [Order article via Infotrieve]
11. Rötig A, de Lonlay P, Chretien D, et al. Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich’s ataxia. Nat Genet. 1997;17:215–217.[Medline] [Order article via Infotrieve]
12.
Babcock M, de Silva D, Oaks R, et al. Regulation of
mitochondrial iron accumulation by Yfh1p, a putative homolog of
frataxin. Science. 1997;276:1709–1712.
13. Miyatake K, Yamagishi M, Tanaka N, et al. New method for evaluating left ventricular wall motion by color-coded tissue Doppler imaging: in vitro and in vivo studies. J Am Coll Cardiol. 1995;25:717–724.[Abstract]
14. Donovan CL, Armstrong WF, Bach DS. Quantitative Doppler tissue imaging of the left ventricular myocardium: validation in normal subjects. Am Heart J. 1995;130:100–104.[Medline] [Order article via Infotrieve]
15. Palka P, Lange A, Fleming AD, et al. Doppler tissue imaging: myocardial wall motion velocities in normal subjects. J Am Soc Echocardiogr. 1995;8:659–668.[Medline] [Order article via Infotrieve]
16. Gorcsan J, Gulati VK, Mandarino WA, et al. Color-coded measures of myocardial velocity throughout the cardiac cycle by tissue Doppler imaging to quantify regional left ventricular function. Am Heart J. 1996;131:1203–1213.[Medline] [Order article via Infotrieve]
17. Gorcsan J, Deswal A, Mankad S, et al. Quantification of the myocardial response to low-dose dobutamine using tissue Doppler echocardiographic measures of velocity and velocity gradient. Am J Cardiol. 1998;81:615–623.[Medline] [Order article via Infotrieve]
18.
Fleming AD, Xia X, McDicken WN, et al. Myocardial
velocity gradients detected by Doppler imaging. Br J
Radiol. 1994;67:679–688.
19.
Palka P, Lange A, Fleming AD, et al. Age-related
transmural peak mean velocities and peak velocity gradients by
Doppler myocardial imaging in normal subjects. Eur Heart
J. 1996;17:940–950.
20. Uematsu M, Nakatani S, Yamagishi M, et al. Usefulness of myocardial velocity gradient derived from two-dimensional tissue Doppler imaging as an indicator of regional myocardial contraction independent of translational motion assessed in atrial septal defect. Am J Cardiol. 1997;79:237–241.[Medline] [Order article via Infotrieve]
21. Palka P, Lange A, Fleming AD, et al. Differences in myocardial velocity gradient measured throughout the cardiac cycle in patients with hypertrophic cardiomyopathy, athletes and patients with left ventricular hypertrophy due to hypertension. J Am Coll Cardiol. 1997;30:760–768.[Abstract]
22.
Shimizu Y, Uematsu M, Simizu H, et al. Peak negative
myocardial velocity gradient in early diastole as a
noninvasive indicator of left ventricular
diastolic function. J Am Coll Cardiol. 1998;32:1418–1425.
23.
Sahn DJ, DeMaria A, Kisslo J, et al. Recommendations
regarding quantitation in M-mode echocardiography:
results of a survey of echocardiographic measurements.
Circulation. 1978;58:1072–1083.
24. Appleton CP, Hatle LK, Popp RL. Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coll Cardiol. 1988;12:426–440.[Abstract]
25. Lange A, Palka P, Caso P, et al. Doppler myocardial imaging vs B-mode grey-scale imaging: a comparative in vitro and in vivo study into their relative efficacy in endocardial boundary detection. Ultrasound Med Biol. 1997;23:69–75.[Medline] [Order article via Infotrieve]
26. Yamada H, Oki T, Mishiro Y, et al. Effect of aging on diastolic left ventricular myocardial velocities measured by pulsed tissue Doppler imaging in healthy subjects. J Am Soc Echocardiogr. 1999;12:574–581.[Medline] [Order article via Infotrieve]
27. Palka P, Lange A, Nihoyannopoulos P. The effect of long-term training on age-related left ventricular changes by Doppler myocardial velocity gradient. Am J Cardiol. 1999;84:1061–1067.[Medline] [Order article via Infotrieve]
28.
Durr A, Cossee M, Agid Y, et al. Clinical and genetic
abnormalities in patients with Friedreich’s ataxia. N Engl
J Med. 1996;335:1169–1175.
29. Filla A, De Michele G, Cavalcanti F, et al. The relationship between trinucleotide (GAA) repeat length and clinical features in Friedreich’s ataxia. Am J Hum Genet. 1996;59:554–560.[Medline] [Order article via Infotrieve]
30.
Isnard R, Kalotka H, Durr A, et al. Correlation between
left ventricular hypertrophy and GAA
trinucleotide repeat length in Friedreich’s ataxia.
Circulation. 1997;95:2247–2249.
31. Lanzillo JJ, Kong XJ, Fanburg BL. A competitive deletion mutant quantitative PCR assay for angiotensin-converting enzyme mRNA in smooth muscle cells. PCR Methods Appl. 1994;4:167–171.[Medline] [Order article via Infotrieve]
32. Uematsu M, Miyatake K, Tanaka N, et al. Myocardial velocity gradient as a new indicator of regional left ventricular contraction: detection by a two-dimensional tissue Doppler imaging technique. J Am Coll Cardiol. 1995;26:217–223.[Abstract]
33. Wilson RB, Roof DM. Respiratory deficiency due to loss of mitochondrial DNA in yeast lacking the frataxin homologue. Nat Genet. 1997;16:352–357.[Medline] [Order article via Infotrieve]
34. Hasan A, McDonough KH. Effects of short term ischemia and reperfusion on coronary vascular reactivity and myocardial function. Life Sci. 1995;57:2171–2185.[Medline] [Order article via Infotrieve]
35.
Ben Hamida M, Belal S, Sirugo G, et al. Friedreich’s
ataxia phenotype not linked to chromosome 9 and associated with
selective autosomal recessive vitamin E deficiency in two inbred
Tunisian families. Neurology. 1993;43:2179–2183.
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 G. D. Buckberg, A. Mahajan, B. Jung, M. Markl, J. Hennig, and M. Ballester-Rodes MRI myocardial motion and fiber tracking: a confirmation of knowledge from different imaging modalities Eur. J. Cardiothorac. Surg., April 1, 2006; 29(Suppl_1): S165 - S177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. De Backer, D. Matthys, T.C. Gillebert, A. De Paepe, and J. De Sutter The use of Tissue Doppler Imaging for the assessment of changes in myocardial structure and function in inherited cardiomyopathies Eur J Echocardiogr, August 1, 2005; 6(4): 243 - 250. [Abstract] [Full Text] [PDF]
|
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P. Palka, A. Lange, J. Atherton, W. J. Stafford, and D. J. Burstow Biventricular diastolic behaviour in patients with hypertrophic and hereditary hemochromatosis cardiomyopathies Eur J Echocardiogr, October 1, 2004; 5(5): 356 - 366. [Abstract] [Full Text] [PDF]
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S.H Poulsen, P Sogaard, J.E Nielsen-Kudsk, and H Egeblad Dilated Cardiomyopathy in Friedreich's Ataxia: 2D Echo and Tissue-Doppler Analysis of Left Ventricular and Atrial Function Eur J Echocardiogr, December 1, 2003; 4(4): 331 - 333. [Full Text] [PDF]
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T H Marwick Clinical applications of tissue Doppler imaging: a promise fulfilled Heart, December 1, 2003; 89(12): 1377 - 1378. [Abstract] [Full Text] [PDF]
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D Pellerin, R Sharma, P Elliott, and C Veyrat Tissue Doppler, strain, and strain rate echocardiography for the assessment of left and right systolic ventricular function Heart, November 1, 2003; 89(90003): iii9 - 17. [Abstract] [Full Text] [PDF]
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Z. Y. Fang, O. Najos-Valencia, R. Leano, and T. H. Marwick Patients with early diabetic heart disease demonstrate a normal myocardial response to dobutamine J. Am. Coll. Cardiol., August 6, 2003; 42(3): 446 - 453. [Abstract] [Full Text] [PDF]
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