- Email: [email protected]
CMR Imaging of Extracellular Volume and Myocardial Strain in Hypertensive Heart Disease∗
JACC: CARDIOVASCULAR IMAGING
VOL. 8, NO. 2, 2015
ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 1936-878X/$36.00
PUBLISHED BY ELSEVIER INC.
http://dx.doi.org/10.1016/j.jcmg.2014.12.002
EDITORIAL COMMENT
CMR Imaging of Extracellular Volume and Myocardial Strain in Hypertensive Heart Disease* William H. Gaasch, MD,y Gerard P. Aurigemma, MDz
P
ressure overload of the left ventricle as occurs
parameters (systolic and diastolic strains). They
in systemic arterial hypertension and aortic
studied a relatively small number of hypertensive
stenosis generally results in an adaptive
patients, some with and some without LVH, and a
left ventricular (LV) hypertrophic remodeling in a
control group of healthy volunteers. They found that
concentric pattern (1). This pattern is defined by an
the ECV was significantly higher in the group with
increased LV wall thickness or wall mass with a
hypertension and hypertrophy (HTN þ LVH) than in
normal end diastolic volume (2). However, not all
the other 2 groups. This increase in ECV, implying
pressure overload results in such concentric remodel-
fibrosis, was associated with reduced myocardial
ing of the ventricle. For example, some patients with
shortening (systolic strain) in both circumferential
hypertension (HTN) exhibit an eccentric remodeling
and radial planes; it was also associated with reduced
pattern with normal systolic function (3). Other pa-
lengthening rate (diastolic strain rate). These strains
tients with aortic stenosis seem to maintain normal
show considerable variability, but they do exhibit
LV systolic performance despite the lack of a compen-
statistically
satory hypertrophic response (4). Still others with
increased ECV. Obviously such associations and cor-
pressure overload hypertrophy and normal LV global
relations do not prove cause and effect, but they do
function exhibit abnormalities of regional function
confirm data published by others and they emphasize
(5). Recognizing the importance of these and other
the potential that CMR holds for studies of cardiac
studies of LV volume, mass, and function in left ven-
remodeling.
significant
correlations
with
the
tricular hypertrophy (LVH), it is relevant to examine
In patients with HTN, the increase in LV wall mass
the changes that develop in the cardiac interstitium
and the “diffuse fibrosis” reported by Kuruvilla et al.
and to relate the findings to other pathophysiological
(7) produces a substrate for diastolic dysfunction and
data, clinical outcomes, and therapeutic interven-
diastolic heart failure. It should be emphasized,
tions (6).
however, that the diastolic properties of the myocarSEE PAGE 172
In this issue of iJACC, Kuruvilla et al. (7) used cardiac magnetic resonance (CMR) imaging techniques to describe an association between extracellular volume (ECV, a surrogate for interstitial fibrosis) and myocardial shortening and lengthening
dium are not determined only by the volume of the ECV. The composition of the ECV is also important. For example, fibrillar components (collagen, elastin), basement membrane proteins (laminin, fibronectin), and nonfibrillar components, as well as the nature and extent of collagen cross linking all play a role in determining myocardial stiffness. It should also be recognized that isoform switches and the phosphor-
*Editorials published in JACC: Cardiovascular Imaging reflect the views of
ylation state of titin within the cardiomyocyte affect
the authors and do not necessarily represent the views of JACC:
myocardial passive stiffness. Indeed, some experi-
Cardiovascular Imaging or the American College of Cardiology.
mental data indicate that increased titin-based stiff-
From the yDepartment of Cardiovascular Medicine, Lahey Hospital
ness is sufficient to cause diastolic dysfunction in
and Medical Center, Tufts University School of Medicine, Boston,
the absence of changes in the extracellular matrix
Massachusetts; and the zDepartment of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts. Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
composition or matrix-based stiffness (8). Certainly, the passive stiffness of the whole ventricle is influenced by the stiffness of the LV wall
182
Gaasch and Aurigemma
JACC: CARDIOVASCULAR IMAGING, VOL. 8, NO. 2, 2015 FEBRUARY 2015:181–3
Editorial Comment
(combined stiffness of the myocytes and the inter-
remodeling and load changes or a true functional
stitium), but it should also be emphasized that LV
abnormality (12,13). It is possible that alterations in
stiffness is affected by the ratio of LV wall mass to
myocardial calcium homeostasis, which is disturbed
chamber volume (M/V). A large body of literature
in LVH, might contribute to abnormal myocardial
developed over the past several decades indicates
strains. It is also possible that the tethering effect of a
that the M/V in normal hearts ranges from 1 to 1.5 (2).
fibrotic interstitium on the cardiomyocytes might
Deviations from this normal range are generally
affect strain.
determined by the type of LV overload or injury so
It should also be recognized that all strain mea-
that the ratio tends to be low in dilated cardiomyop-
surements, both linear strains (eg, myocardial short-
athy
(eccentric
ening and lengthening) and volume strains (eg, LV
remodeling/hypertrophy) and high in aortic stenosis
ejection fraction and filling rate), are influenced by
or systemic arterial hypertension (concentric remod-
the prevailing hemodynamic loads. Loading condi-
eling/hypertrophy).
tions affect strain measurements made by contrast or
or
chronic
mitral
regurgitation
In the paper by Kuruvilla et al. (7), the HTN þ LVH
radionuclide angiography, echocardiography, as well
group exhibited an M/V ratio that was greater than
as CMR. As a result, chamber filling and myocardial
that seen in the normal control group, but the values
lengthening rates have largely been discarded in
in all 3 groups are lower than expected and less
clinical research because of their well-recognized
than that reported by others using similar CMR
load dependency (14,15). Strain abnormalities in
techniques (9). The low M/V cannot be explained
LVH may indicate that something is amiss, but the
by an increased end-diastolic volume because the
mechanisms that underlie such changes in regional
volume (approximately 65 ml/m 2 body surface area
strain remain to be isolated and clarified.
in all 3 groups) was well within the range of normal.
If the composition of the ECV could be better
By contrast, the LV mass in the control group was
defined, the measurement of this space with CMR
relatively low (49 g/m2) and only mildly increased in
might be more meaningful and potentially useful in
the HTN þ LVH group (83 g/m2 ). Measurements of LV
studies of patients with heart failure, particularly
mass and especially the M/V ratio vary considerably
those with diastolic heart failure. For example, an
depending on whether or not the trabecular and
increased ECV could be a relatively stable clue to
papillary muscle mass is or is not included in the
the presence of diastolic dysfunction (in contrast
calculation of wall mass (10,11). This issue may be a
to echocardiographic and other dynamic indices of
problem in other published studies, but it is unlikely
diastolic function that are sensitive to a variety of
to explain the low M/V ratios described by Kuruvilla
hemodynamic loads). An increase in ECV might be
et al. (7) because they specified that the papillary
of diagnostic value if it could confirm a cardiac
muscle mass was included in the total wall mass.
abnormality that is not apparent in a patient with a
Thus, the low M/V ratios in this study are a conse-
normal LV mass and inconclusive Doppler echocar-
quence of a low LV mass which is unexplained. This is
diographic data. Therapeutic trials could use CMR to
an important issue because ECV (expressed as a
follow changes in the ECV. Recognizing that addi-
percent of the LV mass) will be overestimated if the
tional refinement and validation is necessary, CMR
mass calculations underestimate the true LV wall
assessment of the interstitium will continue to play
mass.
a significant role in clinical investigation.
Regional strain abnormalities in hypertrophic heart disease have been described by others, but the cause
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
of such abnormalities remains uncertain. It has not
William H. Gaasch, Lahey Clinic, 41 Mall Road,
been established whether the strain abnormalities
Burlington, Massachusetts 02466. E-mail: william.h.
seen in LVH are a consequence of the LV geometric
[email protected].
REFERENCES 1. Grossman W, Jones D, McLaurin L. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest 1975;56:56–64.
geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med 1991;114:345–52.
2. Gaasch WH, Zile MR. Left ventricular structural
4. Kupari M, Turto H, Lommi J. Left ventricular
remodeling in health and disease: with special emphasis on volume, mass and geometry. J Am Coll Cardiol 2011;58:1733–40.
hypertrophy in aortic valve stenosis: preventive or promotive of systolic dysfunction and heart failure. Eur Heart J 2005;26:1790–6.
3. Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation of left ventricular mass and
5. Narayannan A, Aurigemma GP, Chinali M, Hill JC, Meyer TE, Tighe DA. Cardiac mechanics in mild
hypertensive heart disease. A speckle-strain imaging study. Circ Cardiovasc Imaging 2009;2:382–90. 6. Schelbert EB, Fonarow GC, Bonow RO, Butler J, Gheorghiade GC. Therapeutic targets in heart failure: refocusing on the myocardial interstitium. J Am Coll Cardiol 2014;63:2188–98. 7. Kuruvilla S, Janardhanan R, Antkowiak P, et al. Increased extracellular volume and altered mechanics are associated with LVH in hypertensive
JACC: CARDIOVASCULAR IMAGING, VOL. 8, NO. 2, 2015 FEBRUARY 2015:181–3
heart disease, not hypertension alone. J Am Coll Cardiol Img 2015;8:172–80. 8. Chung CS, Hutchinson KR, Methawasin M, et al. Shortening of the elastic tandem immunoglobulin segment of titin leads to diastolic dysfunction. Circulation 2013;128:19–28. 9. Su M-YM, Lin L-Y, Tseng Y-HE, et al. CMRverified diffuse myocardial fibrosis is associated with diastolic dysfunction in HFpEF. J Am Coll Cardiol Img 2014;7:991–7. 10. Chuang ML, Gona P, Hautvast GLTF, et al. Correlation of trabeculae and papillary muscles with clinical and cardiac characteristics and impact on CMR measures of LV anatomy and function. J Am Coll Cardiol Img 2012;5:1115–23.
Gaasch and Aurigemma Editorial Comment
11. Zile MR, Gaasch WH, Patel K, Aban I, Ahmed A. Adverse left ventricular remodeling in community dwelling older adults predicts incident heart failure and mortality. J Am Coll Cardiol HF 2014;2:
14. Zile MR, Gaasch WH. Mechanical loads and the isovolumic and filling indices of left ventricular relaxation. Progress Cardiovascular Disease 1990; 31:333–46.
512–22.
15. Opdahl A, Remme EW, Helle-Valle T, Lyseggen E, Edvardsen T, Smiseth OA. De-
12. Aurigemma GP, Zile MR, Gaasch WH. Contractile behavior of the left ventricle in diastolic heart failure: with special emphasis on regional systolic function. Circulation 2006; 113:296–304. 13. Baltabaeva A, Marciniak M, Bijnens B, et al. Regional left ventricular deformation and geometry analysis provides insights in myocardial remodeling in mild to moderate hypertension. Euro J Echocardiography 2008;9:501–8.
terminants of left ventricular early-diastolic lengthening velocity: independent contributions from left ventricular relaxation, restoring forces, and lengthening load. Circulation 2009; 119:2578–86.
KEY WORDS cardiac magnetic resonance, extracellular volume, hypertension, left ventricular hypertrophy, T1 mapping
183
VOL. 8, NO. 2, 2015
ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 1936-878X/$36.00
PUBLISHED BY ELSEVIER INC.
http://dx.doi.org/10.1016/j.jcmg.2014.12.002
EDITORIAL COMMENT
CMR Imaging of Extracellular Volume and Myocardial Strain in Hypertensive Heart Disease* William H. Gaasch, MD,y Gerard P. Aurigemma, MDz
P
ressure overload of the left ventricle as occurs
parameters (systolic and diastolic strains). They
in systemic arterial hypertension and aortic
studied a relatively small number of hypertensive
stenosis generally results in an adaptive
patients, some with and some without LVH, and a
left ventricular (LV) hypertrophic remodeling in a
control group of healthy volunteers. They found that
concentric pattern (1). This pattern is defined by an
the ECV was significantly higher in the group with
increased LV wall thickness or wall mass with a
hypertension and hypertrophy (HTN þ LVH) than in
normal end diastolic volume (2). However, not all
the other 2 groups. This increase in ECV, implying
pressure overload results in such concentric remodel-
fibrosis, was associated with reduced myocardial
ing of the ventricle. For example, some patients with
shortening (systolic strain) in both circumferential
hypertension (HTN) exhibit an eccentric remodeling
and radial planes; it was also associated with reduced
pattern with normal systolic function (3). Other pa-
lengthening rate (diastolic strain rate). These strains
tients with aortic stenosis seem to maintain normal
show considerable variability, but they do exhibit
LV systolic performance despite the lack of a compen-
statistically
satory hypertrophic response (4). Still others with
increased ECV. Obviously such associations and cor-
pressure overload hypertrophy and normal LV global
relations do not prove cause and effect, but they do
function exhibit abnormalities of regional function
confirm data published by others and they emphasize
(5). Recognizing the importance of these and other
the potential that CMR holds for studies of cardiac
studies of LV volume, mass, and function in left ven-
remodeling.
significant
correlations
with
the
tricular hypertrophy (LVH), it is relevant to examine
In patients with HTN, the increase in LV wall mass
the changes that develop in the cardiac interstitium
and the “diffuse fibrosis” reported by Kuruvilla et al.
and to relate the findings to other pathophysiological
(7) produces a substrate for diastolic dysfunction and
data, clinical outcomes, and therapeutic interven-
diastolic heart failure. It should be emphasized,
tions (6).
however, that the diastolic properties of the myocarSEE PAGE 172
In this issue of iJACC, Kuruvilla et al. (7) used cardiac magnetic resonance (CMR) imaging techniques to describe an association between extracellular volume (ECV, a surrogate for interstitial fibrosis) and myocardial shortening and lengthening
dium are not determined only by the volume of the ECV. The composition of the ECV is also important. For example, fibrillar components (collagen, elastin), basement membrane proteins (laminin, fibronectin), and nonfibrillar components, as well as the nature and extent of collagen cross linking all play a role in determining myocardial stiffness. It should also be recognized that isoform switches and the phosphor-
*Editorials published in JACC: Cardiovascular Imaging reflect the views of
ylation state of titin within the cardiomyocyte affect
the authors and do not necessarily represent the views of JACC:
myocardial passive stiffness. Indeed, some experi-
Cardiovascular Imaging or the American College of Cardiology.
mental data indicate that increased titin-based stiff-
From the yDepartment of Cardiovascular Medicine, Lahey Hospital
ness is sufficient to cause diastolic dysfunction in
and Medical Center, Tufts University School of Medicine, Boston,
the absence of changes in the extracellular matrix
Massachusetts; and the zDepartment of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts. Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
composition or matrix-based stiffness (8). Certainly, the passive stiffness of the whole ventricle is influenced by the stiffness of the LV wall
182
Gaasch and Aurigemma
JACC: CARDIOVASCULAR IMAGING, VOL. 8, NO. 2, 2015 FEBRUARY 2015:181–3
Editorial Comment
(combined stiffness of the myocytes and the inter-
remodeling and load changes or a true functional
stitium), but it should also be emphasized that LV
abnormality (12,13). It is possible that alterations in
stiffness is affected by the ratio of LV wall mass to
myocardial calcium homeostasis, which is disturbed
chamber volume (M/V). A large body of literature
in LVH, might contribute to abnormal myocardial
developed over the past several decades indicates
strains. It is also possible that the tethering effect of a
that the M/V in normal hearts ranges from 1 to 1.5 (2).
fibrotic interstitium on the cardiomyocytes might
Deviations from this normal range are generally
affect strain.
determined by the type of LV overload or injury so
It should also be recognized that all strain mea-
that the ratio tends to be low in dilated cardiomyop-
surements, both linear strains (eg, myocardial short-
athy
(eccentric
ening and lengthening) and volume strains (eg, LV
remodeling/hypertrophy) and high in aortic stenosis
ejection fraction and filling rate), are influenced by
or systemic arterial hypertension (concentric remod-
the prevailing hemodynamic loads. Loading condi-
eling/hypertrophy).
tions affect strain measurements made by contrast or
or
chronic
mitral
regurgitation
In the paper by Kuruvilla et al. (7), the HTN þ LVH
radionuclide angiography, echocardiography, as well
group exhibited an M/V ratio that was greater than
as CMR. As a result, chamber filling and myocardial
that seen in the normal control group, but the values
lengthening rates have largely been discarded in
in all 3 groups are lower than expected and less
clinical research because of their well-recognized
than that reported by others using similar CMR
load dependency (14,15). Strain abnormalities in
techniques (9). The low M/V cannot be explained
LVH may indicate that something is amiss, but the
by an increased end-diastolic volume because the
mechanisms that underlie such changes in regional
volume (approximately 65 ml/m 2 body surface area
strain remain to be isolated and clarified.
in all 3 groups) was well within the range of normal.
If the composition of the ECV could be better
By contrast, the LV mass in the control group was
defined, the measurement of this space with CMR
relatively low (49 g/m2) and only mildly increased in
might be more meaningful and potentially useful in
the HTN þ LVH group (83 g/m2 ). Measurements of LV
studies of patients with heart failure, particularly
mass and especially the M/V ratio vary considerably
those with diastolic heart failure. For example, an
depending on whether or not the trabecular and
increased ECV could be a relatively stable clue to
papillary muscle mass is or is not included in the
the presence of diastolic dysfunction (in contrast
calculation of wall mass (10,11). This issue may be a
to echocardiographic and other dynamic indices of
problem in other published studies, but it is unlikely
diastolic function that are sensitive to a variety of
to explain the low M/V ratios described by Kuruvilla
hemodynamic loads). An increase in ECV might be
et al. (7) because they specified that the papillary
of diagnostic value if it could confirm a cardiac
muscle mass was included in the total wall mass.
abnormality that is not apparent in a patient with a
Thus, the low M/V ratios in this study are a conse-
normal LV mass and inconclusive Doppler echocar-
quence of a low LV mass which is unexplained. This is
diographic data. Therapeutic trials could use CMR to
an important issue because ECV (expressed as a
follow changes in the ECV. Recognizing that addi-
percent of the LV mass) will be overestimated if the
tional refinement and validation is necessary, CMR
mass calculations underestimate the true LV wall
assessment of the interstitium will continue to play
mass.
a significant role in clinical investigation.
Regional strain abnormalities in hypertrophic heart disease have been described by others, but the cause
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
of such abnormalities remains uncertain. It has not
William H. Gaasch, Lahey Clinic, 41 Mall Road,
been established whether the strain abnormalities
Burlington, Massachusetts 02466. E-mail: william.h.
seen in LVH are a consequence of the LV geometric
[email protected].
REFERENCES 1. Grossman W, Jones D, McLaurin L. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest 1975;56:56–64.
geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med 1991;114:345–52.
2. Gaasch WH, Zile MR. Left ventricular structural
4. Kupari M, Turto H, Lommi J. Left ventricular
remodeling in health and disease: with special emphasis on volume, mass and geometry. J Am Coll Cardiol 2011;58:1733–40.
hypertrophy in aortic valve stenosis: preventive or promotive of systolic dysfunction and heart failure. Eur Heart J 2005;26:1790–6.
3. Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation of left ventricular mass and
5. Narayannan A, Aurigemma GP, Chinali M, Hill JC, Meyer TE, Tighe DA. Cardiac mechanics in mild
hypertensive heart disease. A speckle-strain imaging study. Circ Cardiovasc Imaging 2009;2:382–90. 6. Schelbert EB, Fonarow GC, Bonow RO, Butler J, Gheorghiade GC. Therapeutic targets in heart failure: refocusing on the myocardial interstitium. J Am Coll Cardiol 2014;63:2188–98. 7. Kuruvilla S, Janardhanan R, Antkowiak P, et al. Increased extracellular volume and altered mechanics are associated with LVH in hypertensive
JACC: CARDIOVASCULAR IMAGING, VOL. 8, NO. 2, 2015 FEBRUARY 2015:181–3
heart disease, not hypertension alone. J Am Coll Cardiol Img 2015;8:172–80. 8. Chung CS, Hutchinson KR, Methawasin M, et al. Shortening of the elastic tandem immunoglobulin segment of titin leads to diastolic dysfunction. Circulation 2013;128:19–28. 9. Su M-YM, Lin L-Y, Tseng Y-HE, et al. CMRverified diffuse myocardial fibrosis is associated with diastolic dysfunction in HFpEF. J Am Coll Cardiol Img 2014;7:991–7. 10. Chuang ML, Gona P, Hautvast GLTF, et al. Correlation of trabeculae and papillary muscles with clinical and cardiac characteristics and impact on CMR measures of LV anatomy and function. J Am Coll Cardiol Img 2012;5:1115–23.
Gaasch and Aurigemma Editorial Comment
11. Zile MR, Gaasch WH, Patel K, Aban I, Ahmed A. Adverse left ventricular remodeling in community dwelling older adults predicts incident heart failure and mortality. J Am Coll Cardiol HF 2014;2:
14. Zile MR, Gaasch WH. Mechanical loads and the isovolumic and filling indices of left ventricular relaxation. Progress Cardiovascular Disease 1990; 31:333–46.
512–22.
15. Opdahl A, Remme EW, Helle-Valle T, Lyseggen E, Edvardsen T, Smiseth OA. De-
12. Aurigemma GP, Zile MR, Gaasch WH. Contractile behavior of the left ventricle in diastolic heart failure: with special emphasis on regional systolic function. Circulation 2006; 113:296–304. 13. Baltabaeva A, Marciniak M, Bijnens B, et al. Regional left ventricular deformation and geometry analysis provides insights in myocardial remodeling in mild to moderate hypertension. Euro J Echocardiography 2008;9:501–8.
terminants of left ventricular early-diastolic lengthening velocity: independent contributions from left ventricular relaxation, restoring forces, and lengthening load. Circulation 2009; 119:2578–86.
KEY WORDS cardiac magnetic resonance, extracellular volume, hypertension, left ventricular hypertrophy, T1 mapping
183