Download A 4-Tiered Classification of Left Ventricular Hypertrophy

A 4-Tiered Classification of Left Ventricular Hypertrophy
Based on Left Ventricular Geometry
The Dallas Heart Study
Michel G. Khouri, MD; Ronald M. Peshock, MD; Colby R. Ayers, MS;
James A. de Lemos, MD; Mark H. Drazner, MD, MSc
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Background—Left ventricular hypertrophy (LVH) is traditionally classified as concentric or eccentric, based on the ratio
of LV wall thickness to chamber dimension. We propose a 4-tiered LVH classification based on LV concentricity0.67
(mass/end-diastolic volume0.67) and indexed LV end-diastolic volume (EDV).
Methods and Results—Cardiac MRI was performed in 2803 subjects and LVH (n⫽895) was defined by increased LV
mass/height2.7. Increased concentricity0.67 and indexed EDV were defined at the 97.5th percentile of a healthy subpopulation.
Four geometric patterns resulted: increased concentricity without increased EDV (“thick hypertrophy,” n⫽361); increased
EDV without increased concentricity (“dilated hypertrophy,” n⫽53); increased concentricity with increased EDV (“both thick
and dilated hypertrophy,” n⫽13); and neither increased concentricity nor increased EDV (“indeterminate hypertrophy,”
n⫽468). Compared with subjects with isolated thick hypertrophy, those with both thick and dilated hypertrophy had a lower
LV ejection fraction and higher NT-pro-BNP and BNP levels (Pⱕ0.001 for all). Subjects with dilated hypertrophy had a
lower LV ejection fraction and higher troponin T, NT-pro-BNP, and BNP levels versus those with indeterminate hypertrophy
(P⬍0.001 for all). Subjects with indeterminate LVH versus those without LVH had increased LV mass (by definition) but
also a higher LV ejection fraction and no increase in troponin or natriuretic peptide levels.
Conclusions—Concentric or eccentric LVH can each be subclassified into 2 subgroups, yielding 4 distinct geometric
patterns. Many subjects currently classified with eccentric LVH can be reclassified into an indeterminate subgroup that
has better LV function and comparable levels of biomarkers reflecting cardiac stress as compared with those without
LVH. (Circ Cardiovasc Imaging. 2010;3:164-171.)
Key Words: heart failure 䡲 hypertrophy 䡲 MRI 䡲 remodeling 䡲 cardiac volume
L
eft ventricular hypertrophy (LVH), as defined by increased ventricular mass, can occur either through ventricular dilation or wall thickening. To discriminate these
patterns of hypertrophy, LVH has been subclassified based on
the relative wall thickness (RWT), which is the relative
thickness of the LV wall in proportion to the diameter of the
ventricular chamber.1 When this ratio is increased, the hypertrophy is termed “concentric”; when this ratio is not increased, the hypertrophy is termed “eccentric.” Although this
2-tiered classification has been widely used, its ability to add
prognostic information beyond simple measure of LV mass is
uncertain.2– 8
dimension, a linear parameter, to reflect the LV volume. In
part, this reflects that M-mode and 2D echocardiography are
the imaging modalities used most often to assess LVH, and
these modalities are better suited to measuring LV diastolic
dimension than LV end-diastolic volume (EDV).
To address these limitations, we have developed a new
classification of LVH based on whether or not LV concentricity
(to reflect wall thickness) and LVEDV are increased. This
approach leads to a 4-tiered classification of LVH: (1) increased
concentricity without increased LVEDV (“thick hypertrophy”);
(2) increased LVEDV without increased concentricity (“dilated
hypertrophy”); (3) increased concentricity with increased
LVEDV (“both thick and dilated hypertrophy”); and (4) neither
increased concentricity nor increased LVEDV (“indeterminate
hypertrophy”; because such subjects did not meet criteria either
for significant LV dilation or increased wall thickness it could
not be determined which pattern of hypertrophy predominated).
Our hypothesis was that this approach would provide a more
refined assessment of the geometric patterns of increased LV
mass. The Dallas Heart Study (DHS)9 provided an ideal oppor-
Editorial see p 129
Clinical Perspective on p 171
In considering this issue, we noted that there are 2 potential
limitations with the present 2-tiered classification of LVH.
First, it does not isolate independent changes in ventricular
dilation and wall thickening but rather depends on their ratio.
Second, RWT relies on measurement of the LV diastolic
Received May 29, 2009; accepted December 7, 2009.
From the Donald W. Reynolds Cardiovascular Clinical Research Center and Divisions of Cardiology, Department of Internal Medicine, University of
Texas Southwestern Medical Center, Dallas, Tex.
Correspondence to Mark H. Drazner, MD, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9047. E-mail
[email protected]
© 2010 American Heart Association, Inc.
Circ Cardiovasc Imaging is available at http://circimaging.ahajournals.org
164
DOI: 10.1161/CIRCIMAGING.109.883652
Khouri et al
tunity to address this question because subjects underwent
cardiac MRI, a modality with significant advantages over 2D
echocardiography in estimating LV mass10 and volumes.11
Further, because of the extensive phenotyping of DHS subjects,
we were able to compare clinical characteristics and surrogate
markers of risk among these 4 profiles and among those without
LVH. We were specifically interested in determining whether
subclassifying the present 2-tiered system would yield 4 distinct
phenotypes.
Methods
Dallas Heart Study
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The DHS is a population-based, multiethnic, probability sample of
residents of Dallas County, designed to study subclinical cardiovascular disease. Self-reported blacks were intentionally oversampled to
ensure that 50% of the final sample included this ethnic group.
Details of the study design and cohort have been reported elsewhere.9 The study was approved by the University of Texas
Southwestern Medical Center Institutional Review Board, and all
subjects provided written informed consent. The study involved 3
separate visits. The initial in-home visit included 6101 participants
and consisted of demographic and medical history data collection as
well as objective measurements (including blood pressure). Participants largely in the 30- to 65-year age group were invited for a
second in-home visit for collection of fasting blood and urine
samples. Participants completing the second visit had a third visit, at
which time ECG, cardiac MRI, electron beam CT,12 and dual-energy
x-ray absorptiometry scanning studies were performed. In the early
phases of DHS, 96 subjects ages 18 to 29 years were invited to
participate and completed all 3 visits including the cardiac MRI and
are included in this analysis. Overall, a total of 3557 and 3072
subjects completed the second and third visits, respectively. Of these,
2803 participants underwent cardiac MRI.
Cardiac MRI
Cardiac MRI was performed using 2 comparable 1.5-T MRI systems
(Phillips Medical Systems, Best, The Netherlands) as described.13
Briefly, short-axis breath-hold ECG-gated cine MRI were obtained
from the LV apex to base using the following parameters: 6-mm
slice; 4-mm gap; field of view of 36 to 40 cm; acquired pixel size at
36-cm field of view, 1.29⫻2.58; and temporal resolution of 40 ms.
MASS software (Medis Medical Imaging Systems, Leiden, The
Netherlands) was used to analyze data. End-diastolic and end-systolic endocardial and epicardial borders were traced manually to
measure LV cavity and wall volume in each slice. Myocardial mass
was estimated by multiplying the myocardial wall volume at enddiastole by the specific gravity of muscle (1.05 g/mL). The papillary
muscles were included in the myocardial mass and excluded from the
LV volume. Measurements from each slice were summed using the
method of disks. Mean LV wall thickness was determined by
averaging the wall thickness of each short-axis slice (excluding the
apical slice).14 LV ejection fraction (LVEF) was calculated in
standard fashion from the endocardial volumes: LVEF⫽100⫻
(EDV⫺end-systolic volume)/EDV. Interobserver and intraobserver
difference and interscan variability have been described.15
Biomarker Assays
Cardiac troponin T (cTnT) (Roche Diagnostics, Inc, Indianapolis,
Ind), B-type natriuretic peptide (BNP) (Biosite, Inc, San Diego,
Calif) and N-terminal-pro-BNP (NT-pro-BNP) (Roche Diagnostics,
Inc) were measured from thawed frozen plasma samples as reported
previously.16,17
Definition of Variables
Sex, ethnicity, and age were self-reported. Body surface area (BSA)
was calculated with the use of sex-specific equations derived by
Tikuisis et al.18 Diabetes mellitus was defined by a fasting serum
New Classification of LV Geometry in LVH
165
glucose ⱖ126 mg/dL (ⱖ7 mmol/L), nonfasting serum glucose ⱖ200
mg/dL (ⱖ11.1 mmol/L), or self-reported diabetes with use of an
antihyperglycemic medication. Hypertension was defined as a mean
systolic blood pressure (SBP) from the 3 visits of ⱖ140 mm Hg,
mean diastolic blood pressure (DBP) ⱖ90 mm Hg, or use of
antihypertensive medication. Obesity was defined as body mass
index (BMI) ⱖ30 kg/m2. Coronary artery calcium was considered
present when the average Agatston score was ⬎10.12 Sex-specific
threshold values for low LVEF were defined as ⬍0.61 (women) and
⬍0.55 (men).15 History of myocardial infarction15 and chronic heart
failure or cardiomyopathy19 were defined as before.
Defining LV Geometry
Sex-specific values of LVH were defined as previously: LV mass/
height2.7 ⱖ39 g/m2.7 (women) and ⱖ48 g/m2.7 (men).13 To identify
wall thickening, we used a modified formula to calculate concentricity. In considering how the ratio of LV mass to volume would
reflect wall thickness, we noted in a simple geometric assumption
that volume⫽4/3 ␲ ⫻radius 3 , and mass⫽density⫻surface
area⫻thickness⫽density⫻(4 ␲⫻radius2) ⫻thickness. Eliminating
radius from these 2 equations leads to: thickness⫽k mass/volume(2/3),
where k is a constant. In preliminary analyses, the ratio of LV
mass/vol0.67 (herein termed concentricity0.67) was more highly correlated with both LV wall thickness (sex-adjusted r2⫽0.89) and
systolic blood pressure (r2⫽0.42) than was the standard definition of
concentricity (LV mass/LVEDV) (r2⫽0.69 and 0.22, respectively),
and thus concentricity0.67 was used for all analyses. We defined
sex-specific values for increased LVEDV/BSA and for concentricity0.67 as ⱖ97.5th percentile of the previously described healthy
subpopulation used to define LVH13 yielding values of LVEDV/
BSA: ⱖ68 mL/m2 (women) and ⱖ74 mL/m2 (men) and concentricity0.67: ⱖ8.1 g/mL0.67 (women) and ⱖ9.1 g/mL0.67 (men). A 4-tiered
classification of LVH was developed based on whether concentricity0.67 and LVEDV/BSA were increased or not using the above
threshold values. To recapitulate the standard 2-tiered classification,
given that we do not have the 2D measurements necessary for RWT,
we classified concentric hypertrophy when concentricity0.67 was
greater or equal to the above sex-specific thresholds and eccentric
hypertrophy when below those values. In 3 different sensitivity
analyses, we defined LVH based on LV mass/BSA using previously
published values13 and defined increased indexed LVEDV using
ⱖ97.5th percentile of the previously described healthy subpopulation for LVEDV/height (ⱖ70.4 mL/m for women and ⱖ79 mL/m for
men) or LVEDV/BSA1.5 [ⱖ53.3 mL/(m2)1.5 for women and ⱖ55.5
mL/(m2)1.5 for men].
Statistical Analysis
All statistical analyses were performed with the use of SAS version
9.1 (SAS Institute, Inc, Cary, NC) statistical software. Continuous
variables are expressed as mean⫾SD, except for BNP and NT-proBNP levels, which are expressed as median and interquartile ranges.
Categorical variables are expressed as percentages within the geometric group. For continuous variables, statistical comparisons of
variables among the LV geometric categories were tested by 1-way
ANOVA except for comparisons with BNP and NT-pro-BNP, which
were tested with the Kruskal-Wallis test. Differences in categorical
variables among the geometric patterns were evaluated using Pearson ␹2 test. Multiple comparisons were assessed for those variables
that were statistically different across the geometric patterns by the
Tukey method for continuous variables and a resampling, bootstrapping technique for categorical variables. For all statistical testing, a
probability value ⬍0.05 was considered statistically significant.
Results
Four-Tiered Classification of LVH
The resulting 4 patterns of LVH are graphically depicted and
compared with the prior 2-tiered classification and with subjects
without increased LV mass (Figure 1). The newly proposed
4-tiered classification subclassifies eccentric hypertrophy into
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Circ Cardiovasc Imaging
March 2010
Figure 1. Diagrammatic representation of the conventional 2-tiered classification and the newly proposed 4-tiered classification of LVH. Outer circle
represents mean LV mass; inner circle, mean EDV.
Accordingly, the hatched area remaining within the
2 circles reflects concentricity (LV mass/EDV) and
does not represent true wall thickness. LVH is
defined as increased LV mass/height2.7. Previously,
patients with LVH were classified as having concentric hypertrophy (increased RWT) or eccentric
hypertrophy (absence of increased RWT), as
shown at the top of the figure. The newly proposed 4-tiered classification is based on whether
concentricity0.67 is increased (defined as ⱖ8.1
g/mL0.67 in women and ⱖ9.1 g/mL0.67 in men) and
whether LVEDV/BSA is increased (defined as ⱖ68
mL/m2 in women and ⱖ74 mL/m2 in men), as
shown at the bottom of the figure. NA indicates
not applicable.
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dilated hypertrophy or indeterminate hypertrophy and subclassifies concentric hypertrophy into thick hypertrophy or both
thick and dilated hypertrophy. Using this classification, there
were 468 subjects with indeterminate hypertrophy, 53 with
dilated hypertrophy, 361 with thick hypertrophy, and 13 with
both thick and dilated hypertrophy. In a 2-tiered classification
(defining concentric LVH by increased concentricity0.67), the
latter 2 groups would be classified as concentric LVH (n⫽374)
and the former 2 groups as eccentric hypertrophy (n⫽521).
Representative cardiac MRIs from subjects with each LVH
pattern and from a subject without LVH are shown (Figure 2).
Among those without LVH (n⫽1908), 188 (9.9%) had increased
concentricity0.67 as defined, and these subjects would be analogous to those with concentric remodeling in the previous
classification system.1
Association of LVH Pattern With Baseline
Characteristics and Cardiac Structure and Function
Baseline characteristics and measures of cardiac structure and
function are shown stratified by presence and type of LVH
(Table). Systolic blood pressure was higher, and hypertension
was more prevalent among those with thick hypertrophy
(with or without LV dilation) as compared with those without
thick hypertrophy. Participants with thick hypertrophy, as
defined by increased concentricity0.67 (with or without LV
dilation) versus those without thick hypertrophy had a larger
LV wall thickness. Participants with dilated hypertrophy
(with or without thick hypertrophy) versus those without
dilated hypertrophy had lower LVEF. In comparing subjects
with indeterminate LVH with the other subjects with LVH,
the former had a significantly lower LV mass (irrespective of
indexation) and higher LVEF.
Comparison of the 2 Newly Proposed Subgroups
of Subjects With Concentric LVH and of Subjects
With Eccentric LVH
To determine whether the newly created subgroups of concentric hypertrophy (thick hypertrophy versus both thick and
dilated hypertrophy) or eccentric hypertrophy (indeterminate
hypertrophy versus dilated hypertrophy) identified distinct
phenotypes, we compared their association with various
markers of cardiac stress. Subjects with both thick and dilated
hypertrophy as compared with those with isolated thick
hypertrophy had higher prevalence of reduced LVEF (Figure 3A).
The differences in elevated troponin T levels in this comparison did not reach statistical significance (P⫽0.1, Figure 3B),
but those with both thick and dilated hypertrophy did have
higher NT-pro-BNP (Figure 4A) and BNP levels (Figure 4B).
Those with dilated hypertrophy as compared with those with
indeterminate hypertrophy were more likely to have a reduced LVEF (Figure 3A) or elevated troponin T (Figure 3B)
and had higher NT-pro-BNP (Figure 4A) and BNP levels
Figure 2. Representative short-axis cardiac MRI images from subjects in each of the 4 newly proposed patterns of LVH and from a subject
without LVH. All subjects were male to allow comparison among the groups. The images were taken at 100% magnification and placed into
a 1.5⫻1.5-inch square such that the margins of the image were equidistant from the center of LV circle. Values of LV mass/height2.7 (g/m2.7),
LVEDV/BSA (mL/m2), concentricity0.67 (g/mL0.67), and LV wall thickness (mm) for the subjects shown are listed, respectively (no LVH: 46, 54,
8.3, 12; indeterminate: 49, 57, 7.8, 12.3; dilated: 60, 93, 7.3, 12.1; thick: 67, 55, 10.7, 15; both: 64, 87, 9.6, 14.5).
Khouri et al
Table.
New Classification of LV Geometry in LVH
167
Baseline Characteristics Stratified by Presence of LVH and 4-Tiered Geometric Pattern of LVH
LVH
Eccentric
Variable
No LVH
N
Age, y
Male, %
Indeterminate
SBP, mm Hg
Dilated
Thick
P*
1908
468
53
44⫾9
44⫾10
48⫾10†㛳
51⫾8‡
⬍0.001
14
47†
43†
77†
⬍0.001
⬍0.001
41†
122⫾13†
361
Both Thick and Dilated
44⫾10
53†
Black race, %
Concentric
13
54
66
79†
85
128⫾16
130⫾20
145⫾20†§
149⫾16†㛳
⬍0.001
Hypertension, %
24†
38
42
73†§
92†㛳
⬍0.001
Antihypertension, % therapy
15‡
21
31
44†
73‡
⬍0.001
BMI, kg/m
28⫾6†
36⫾7
31⫾8†
36⫾9§
34⫾7
⬍0.001
Obese, %
30†
78
47†
73§
62
⬍0.001
Very obese (BMI ⱖ35), %
2
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11†
49
23†
45㛳
31
0.003
Diabetes, %
8†
13
11
25†
38
⬍0.001
Prior myocardial infarction, %
2
1
9‡
6†
8
⬍0.001
Chronic heart failure/cardiomyopathy, %
1‡
3
19†
8‡
15
37‡
Coronary artery calcium present, %
Wall thickness, mm
19
11.2⫾1.6‡
11.4⫾1
46†**
⬍0.001
37†
25
⬍0.001
12⫾1.5‡
14.4⫾2†§
15.2⫾1†§
⬍0.001
205⫾59†㛳¶
⬍0.001
LV volume, mL
98⫾22†
106⫾21
176⫾56†
102⫾27§
LV volume/BSA, mL/m2
51⫾10
54⫾8
90⫾27
49⫾11
LV mass/height2.7
36⫾6
45⫾5.4
56⫾11
54⫾13
LV mass/BSA, g/m2
79⫾14††
81⫾12
115⫾25†
104⫾25†㛳
150⫾29†§¶
LV mass/fat free mass, g/kg
2.8⫾0.3††
3.1⫾0.3
3.9⫾0.9†
3.6⫾0.8†㛳
4.8⫾0.9†§¶
Concentricity0.67, (g/mL0.67)
7.2⫾1.3
7.2⫾0.8
7.2⫾1
10⫾2
9.6⫾0.7
By definition
Concentricity, g/mL
1.6⫾0.3
1.5⫾0.2
1.3⫾0.2
2.2⫾0.5
1.7⫾0.2
By definition
Stroke volume, mL
70⫾16†
79⫾16
101⫾27†
72⫾19†§
96⫾25‡¶
⬍0.001
LVEF, %
72⫾7†
75⫾6
61⫾18†
71⫾9†§
51⫾19†㛳¶
⬍0.001
92⫾23
By definition
72⫾12
By definition
⬍0.001
⬍0.001
LVH defined by indexation height2.7.
*P for comparison among the 4 patterns of LVH.
†P⬍0.001 versus indeterminate.
‡P⬍0.05 versus indeterminate.
§P⬍0.001 versus dilated.
㛳P⬍0.05 versus dilated.
¶P⬍0.001 versus thick.
**P⬍0.05 versus thick.
††LV mass/BSA and LV mass/FFM in individuals without LVH were significantly lower than those with indeterminate.
(Figure 4B). After excluding subjects with self-reported
history of myocardial infarction and chronic heart failure or
cardiomyopathy, those with dilated hypertrophy (n⫽43) versus those with indeterminate hypertrophy (n⫽445) still had a
higher prevalence of reduced LVEF and elevated troponin as
well as higher BNP and NT-pro-BNP levels (P⬍0.05 for
troponin; all other P⬍0.005).
Comparison of Subjects With Indeterminate
Hypertrophy to Those Without LVH
By definition, subjects with indeterminate LVH had increased
indexed LV mass (⬎97.5th percentile of the healthy subpopulation) but did not meet criteria for thick or dilated hypertrophy (ie, they were ⬍97.5th percentile of the healthy subpopulation for concentricity0.67 and LVEDV/BSA, respectively).
In comparing them with those without LVH, although the
indeterminate LVH group had increased LV mass (by defi-
nition), there were no significant differences between these 2
groups in presence of coronary artery calcium, elevated
troponin, and BNP or NT-pro-BNP levels (Table and Figures
3 and 4). Further, those with indeterminate LVH versus those
without LVH had an increased LVEF.
Sensitivity Analyses to Account for Method of
Indexation When Defining LVH or Increased
LV Volume
We performed 3 sensitivity analyses to verify that our findings
persisted irrespective of indexation method. First, we defined
LVH based on LV mass indexed to BSA rather than height2.7.
There were 2489 subjects without LVH, 44 with dilated hypertrophy, 209 with thick hypertrophy, 55 with indeterminate
hypertrophy, and 13 with both thick and dilated hypertrophy
with this approach. The majority of the key findings noted above
with LVH defined by indexation to height2.7 persisted. Specifi-
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indeterminate hypertrophy (P⬍0.005 for all), and those with
both thick and dilated hypertrophy had higher NT-pro-BNP
levels (P⫽0.05) and lower LVEF (P⬍0.001) than those with
isolated thick hypertrophy. An elevated troponin T was present
in 0.3% of the subjects with indeterminate hypertrophy, which
was significantly lower than among the other 3 patterns (3%
thick, 2% dilated, 5% both thick and dilated, P⫽0.005). In
comparing those with indeterminate hypertrophy versus those
without LVH, there was no significant difference in NT-proBNP (P⫽0.3) levels, and the former had a higher LVEF
(P⬍0.001) than the latter.
Third, we defined increased LVEDV based on indexation
to BSA1.5 rather than BSA.20 Among those subjects with
LVH (defined by height2.7), there were 36 with dilated
hypertrophy, 366 with thick hypertrophy, 485 with indeterminate hypertrophy, and 8 with both thick and dilated
hypertrophy using this approach. Again, key findings from
the primary analysis persisted including that subjects with
dilated hypertrophy had higher natriuretic peptide levels, a
lower LVEF, and more often had elevated troponin levels
compared with those with indeterminate hypertrophy
(P⬍0.005 for all).
Discussion
Figure 3. Prevalence of reduced LVEF (A) and elevated troponin
T (B) in subjects stratified by presence and type of LVH.
Reduced LVEF was defined as ⬍0.61 in women and ⬍0.55 in
men as before.15 Elevated troponin T was defined as ⱖ0.01
␮g/L as before.16 *P⬍0.001 versus indeterminate; †P⬍0.001
versus thick; ‡P⬍0.01 versus indeterminate.
cally, among subjects previously classified as having eccentric
hypertrophy, those with dilated hypertrophy had higher natriuretic peptide levels and lower LVEF than those with indeterminate hypertrophy (Pⱕ0.005 for all). Similarly, among those
formerly classified as having concentric hypertrophy, those with
both thick and dilated hypertrophy versus those with isolated
thick hypertrophy had higher NT-pro-BNP level and lower
LVEF (P⬍0.001 for both) with a trend for a lower BNP level
(P⫽0.07). An elevated troponin T was present in none of the
subjects with indeterminate hypertrophy, and in 5%, 7%, and
15% of the thick, dilated, and both thick and dilated groups,
respectively (P⫽0.08). There were no significant differences in
NT-pro-BNP (P⫽0.2) levels or LVEF (P⫽0.6) in comparing
those with indeterminate hypertrophy with those without LVH
in this analysis.
Next, we defined increased LVEDV based on indexation to
height rather than BSA. Among subjects with LVH (defined
by height2.7), there were 185 with dilated hypertrophy, 308
with thick hypertrophy, 336 with indeterminate hypertrophy,
and 67 with both thick and dilated hypertrophy using this
approach. Again, the majority of the key findings noted above
using the classification based on LVEDV indexed to BSA
persisted. Subjects with dilated hypertrophy had higher natriuretic peptide levels and lower LVEF than those with
The Dallas Heart Study afforded the opportunity to refine
the currently accepted 2-tiered classification of LV geometric patterns because cardiac MRI, a modality known to
offer significant advantages over 2D echocardiography in
estimating LV mass and volume,10,21 was performed on a
large, population-based cohort. Herein we demonstrate
that the present classification of LVH as concentric or
eccentric can be refined into a 4-tiered classification. This
refinement is based on the assessment of ventricular
dilation and increased LV concentricity rather than the
current practice of using the RWT. We found that subjects
with eccentric LVH can be subclassified into 2 distinct
groups: 1 with dilated hypertrophy and a much larger
group without either thick or dilated hypertrophy (indeterminate group). Similarly, subjects with concentric LVH
can be subclassified into those with thick hypertrophy and
those with both thick and dilated hypertrophy. The potential utility of these subclassifications was demonstrated by
finding significant differences in biomarkers reflecting
pathological cardiac stress between the new subgroups,
both in those presently classified as eccentric or concentric
LVH. Further, these conclusions were insensitive to the
method of indexation of LV mass or LVEDV.
Limitations of the Standard 2-Tiered Classification
of LVH
Echocardiographic classification of LV geometry as concentric or eccentric has relied on the RWT.1 Some findings using
this approach have been unexpected or suboptimal. For
example, eccentric hypertrophy was more prevalent than
concentric hypertrophy in hypertensive populations,1,22 contrary to the expected finding in a pressure-overloaded state.
Additionally, the prognostic utility of LV geometry based on
this classification beyond LV mass was uncertain.2–5,7,8 These
Khouri et al
New Classification of LV Geometry in LVH
169
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Figure 4. Plasma NT-pro-BNP (A) and BNP (B)
levels by presence and type of LVH. Median
values, line within the box; interquartile range,
25th and 75th percentiles, lower and upper box
margins, respectively; 5th and 95th percentiles,
lower and upper ends of whiskers, respectively.
*P⬍0.001 versus indeterminate; †P⬍0.005 versus indeterminate; ‡P⬍0.01 versus indeterminate; §P⬍0.001 versus thick; 储P⬍0.05 versus
thick.
data suggest the possibility of a need to refine the present
2-tiered classification of LVH.
Subclassification of Eccentric LVH
When eccentric LVH was classified into 2 subgroups, based
on whether LV dilation was present, 2 distinct phenotypes
appeared. Subjects with dilated hypertrophy versus those with
indeterminate hypertrophy had higher indexed LV mass,
lower LVEF, and higher levels of natriuretic peptides, among
many other differences. The association between increased
LVEDV with a decline in LVEF has been emphasized.23
Whereas eccentric LVH was considered a lower risk profile
versus concentric LVH2,4 in the old classification, such
findings likely were driven by those with indeterminate
hypertrophy and may not be true of those with dilated
hypertrophy.
The proposed subclassification of eccentric LVH will
also affect the relative frequency of thick and dilated
hypertrophy in a population. Using the standard 2-tiered
classification that defines eccentricity by the absence of
concentricity, ⬇60% of the 895 subjects with LVH in the
DHS would have eccentric LVH. Other cohorts using the
2-tiered classification similarly reported an increased frequency of eccentric versus concentric hypertrophy,6 ranging from 1 (men) to 1.5-fold (women) in the Framingham
Heart Study4 to 3.9-fold in the Cardiovascular Health
Study.24 In contrast, with the newly proposed 4-tiered
classification system, thick hypertrophy was 6-fold more
common than dilated hypertrophy, whereas indeterminate
hypertrophy was the most common geometric pattern
observed. These data offer a plausible explanation as to
why eccentric LVH has been reported to be more common
170
Circ Cardiovasc Imaging
March 2010
than concentric LVH in prior studies of hypertensive
populations.
Indeterminate Hypertrophy and Potential
Implications for Defining LVH
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More than 50% of subjects with LVH did not have thick or
dilated hypertrophy (“indeterminate hypertrophy”). Such individuals had increased LV mass as compared with those subjects
without LVH (by definition). They also had increased LV
concentricity, wall thickness, and end-diastolic volume than
those without LVH but not sufficient to meet the criteria for
either thick or dilated hypertrophy. Further, their LV mass was
lowest among the 4 LV geometric patterns (Table).
Interestingly, subjects with indeterminate hypertrophy, as
compared with those subjects without LVH, were not more
likely to have prevalent coronary artery calcium or elevated
troponin or NT-pro-BNP or BNP levels and had a higher
LVEF (Table). In sensitivity analyses, these data largely
persisted regardless of indexation method for LV mass or
volume. Whether these data will translate into equivalent
cardiovascular risk over time in these 2 groups can only be
addressed with longitudinal follow-up. Similarly, it will be
important to determine whether individuals with indeterminate hypertrophy progress to develop thick or dilated hypertrophy, and, if so, to identify risk factors for those transitions.
Regardless, identification of a subgroup of subjects with
increased LV mass that is not associated with detectable
markers of cardiac stress touches on the question on how best
to define LVH. Specifically, these data raise the question as
to whether pathological LVH should only be defined as
present when LV mass is increased and there is evidence of
thick and/or dilated hypertrophy. If such a standard was
implemented in the future, then the 4-tiered classification of
LVH proposed herein would be simplified to a 3-tiered
classification (thick, dilated, or both thick and dilated).
Thick Hypertrophy
Concentricity0.67 was used to define thick hypertrophy in this
study. The relationship between concentricity and pressure
load has been demonstrated in animals and humans.25 In our
study, thick hypertrophy was associated with increased prevalent hypertension and SBP (Table). The majority of subjects
(n⫽361) with increased concentricity did not have dilated
hypertrophy, whereas 13 subjects did have both thick and
dilated hypertrophy. In addition to an increase in LV volume
(required by definition), the latter subjects also had a lower
LVEF (Table and Figure 3A) and higher NT-pro-BNP and
BNP levels (Figure 4A and 4B) than those with isolated thick
hypertrophy. It is of interest that fewer than 5% of subjects
with increased concentricity also had LV dilation, data
consistent with our previous observations suggesting the
transition from concentric LVH to reduced systolic dysfunction is uncommon,26,27 although we recognize the possibility
of survivor bias. Whether thick hypertrophy is a precursor for
combined thick and dilated hypertrophy cannot be ascertained from these cross-sectional data.
Limitations
Several limitations of this study should be noted. First, our study
is cross-sectional and does not have outcome data. Therefore, we
cannot determine whether the newly proposed geometric patterns convey prognostic information, despite their associations
with surrogate markers of risk such as LV ejection fraction,
troponin, and natriuretic peptide levels. Similarly, our data
cannot address whether subjects with LVH in the absence of
thick or dilated hypertrophy have comparable cardiovascular
risk as compared with subjects without LVH. Second, we are
unable to dissect the relative contributions of LV geometric
pattern from LV mass itself. Third, internal LV diameter was not
measured from the baseline MRI study and thus RWT could not
be determined. As such, a direct comparison of subject allocation in the proposed DHS scheme with the current 2-tiered
system of LVH classification by RWT could not be performed.
Instead, we used LV concentricity0.67 as a surrogate for RWT in
such analyses and then defined eccentric LVH by the absence of
elevated concentricity. Fourth, midwall shortening was not
assessed, and this may have affected our assessment of systolic
function in the presence of thick hypertrophy.28 Finally, because
diastolic function was not measured, we could not analyze its
relationship with the proposed 4-tiered LVH classification.
Conclusions
Eccentric and concentric LVH can each be subdivided into 2
further subgroups, based on whether or not LV volume is
increased. These new subgroups appear to have distinct
phenotypes though longitudinal data are necessary to determine whether they convey independent prognostic information. More than one half of subjects who had increased LV
mass did not meet criteria for increased LV concentricity or
ventricular dilation, and these individuals did not have
elevated markers of cardiac stress as compared with subjects
without LVH. These data raise the question whether pathological LVH should be considered present only if LV mass is
increased, and there is also evidence of increased wall
thickness and/or ventricular dilation.
Acknowledgments
We appreciate the assistance of Sachin Gupta, MD, in preparing
Figure 2.
Sources of Funding
The Dallas Heart Study is funded by a center grant from the Donald
W. Reynolds Foundation.
Disclosures
Dr de Lemos has received grant support and consulting income from
Biosite and Roche.
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CLINICAL PERSPECTIVE
Left ventricular hypertrophy (LVH), defined as increased indexed LV mass, is presently classified based on the ratio of the
LV wall thickness to chamber dimension. If this ratio is increased, then the LVH is concentric; otherwise the LVH is
eccentric. We propose a 4-tiered classification based on whether or not LV concentricity0.67 (LV mass/LV end-diastolic
volume0.67 [EDV]) and LVEDV/body surface area are increased. Among 2803 subjects who underwent cardiac MRI, 895
had LVH. Of these, 361 had increased concentricity0.67 but not LVEDV (“thick hypertrophy”), 53 had increased LVEDV
but not concentricity0.67 (“dilated hypertrophy”), 13 had both increased concentricity0.67 and LVEDV (“both thick and
dilated hypertrophy”), and 468 had neither increased concentricity0.67 nor LVEDV (“indeterminate hypertrophy”). Subjects
with both thick and dilated hypertrophy had a lower LV ejection fraction and higher natriuretic peptide levels versus those
with isolated thick hypertrophy. Subjects with indeterminate hypertrophy had a higher LV ejection fraction and lower
troponin T and natriuretic peptide levels versus those with dilated hypertrophy and no increase in troponin T or natriuretic
peptide levels versus those without LVH. We conclude that concentric and eccentric LVH can each be subclassified into
2 distinct subgroups based on the presence of LV dilation. These data question whether LVH should be considered present
only if there is increased LV mass and also increased LV wall thickness and/or ventricular dilation. Refinement of the
phenotypic characterization of LVH may improve our understanding of its natural history and provide an opportunity for
more specific and possibly earlier therapeutic intervention.
A 4-Tiered Classification of Left Ventricular Hypertrophy Based on Left Ventricular
Geometry: The Dallas Heart Study
Michel G. Khouri, Ronald M. Peshock, Colby R. Ayers, James A. de Lemos and Mark H.
Drazner
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Circ Cardiovasc Imaging. 2010;3:164-171; originally published online January 8, 2010;
doi: 10.1161/CIRCIMAGING.109.883652
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