THEMED ARTICLE y Heart Failure Review

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Imaging in hypertensive
heart disease
Expert Rev. Cardiovasc. Ther. 9(2), 199–209 (2011)
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Rajesh Janardhanan1 Hypertensive heart disease is the target organ response to arterial hypertension. Left ventricular
and Christopher M hypertrophy represents an important predictor for cardiovascular events. Myocardial fibrosis, a
Kramer†1 common end point in hypertensive heart disease, has been linked to the development of left
ventricular hypertrophy and diastolic dysfunction. Echocardiography is clinically useful in the
1
Departments of Medicine (Cardiology)
and Radiology and the Cardiovascular
detection of left ventricular hypertrophy and the assessment of diastolic function. Although
Imaging Center, University of Virginia echocardiography is more widely available, cardiac magnetic resonance has been demonstrated
Health System, 1215 Lee St., to be more reproducible for the estimation of left ventricular mass. Future developments in
Box 800170, Charlottesville, cardiac magnetic resonance techniques may facilitate the quantification of diffuse fibrosis that
VA 22908, USA
†
Author for correspondence: occurs in hypertensive heart disease. Thus, advances in cardiac imaging provide comprehensive,
Tel.: +1 434 243 0736 noninvasive tools for imaging left ventricular hypertrophy, diastolic dysfunction, myocardial
Fax: +1 434 982 1998 fibrosis and ischemia observed in hypertensive heart disease. The objective of this article is to
ckramer@virginia.edu
summarize the state-of-the-art and the future of multimodality imaging of hypertensive
heart disease.
For personal use only.

Keywords : cardiac magnetic resonance • diastolic function • echocardiography • hypertension • hypertensive

heart disease • left ventricular hypertrophy • left ventricular mass • myocardial fibrosis

Hypertensive heart disease (HHD) is the tar- improvement in cardiovascular outcomes [7,8] .
get organ response to systemic arterial hyper­ It is therefore important to identify patients
tension. Patients with longstanding hyper­ with LVH, both for prognosis and for tighter
tension are at increased risk for developing left BP control. Ventricular arrhythmias occur
ventricular hypertrophy (LVH) and diastolic more frequently in hypertensive patients  [9] ,
dysfunction [1] . Arterial hypertension repre- with QT dispersion increasing directly with
sents one of the most common risk factors for left ventricular mass (LVM) [10] . There is also
the development of heart failure, conferring a link between HHD and atrial fibrillation,
approximately a twofold increased risk in men whose likelihood increases by 40–50% in the
and a threefold risk in women relative to nor- presence of hypertension [11] . Increased suscep-
motensive subjects [2] . This article summarizes tibility to ischemic heart disease rounds out
the state-of-the-art and the future of multi­ the cardiovascular sequelae of HHD, with a
modality noninvasive imaging in HHD with sixfold higher risk of myocardial infarction in
a focus on imaging LVH, diastolic dysfunction, hypertensive patients than in normotensive
myocardial fibrosis and ischemia secondary individuals [2] .
to hypertension.
Imaging hypertensive LVH
Why is HHD important? LV mass
Left ventricular hypertrophy develops as an The identification of LVH in the hypertensive
initially adaptive response of the normal heart patient is important from a prognostic stand-
to an increased afterload from a variety of rea- point. It identifies the patient with hyperten-
sons, systemic hypertension being the most sion who may require more aggressive BP con-
common. Data from the Framingham Heart trol. In patients with essential hypertension
Study has established LVH as a risk factor for and baseline LVH on ECG, lower LVM during
cardiovascular morbidity and mortality, inde- antihypertensive treatment is associated with
pendent of other cardiovascular risk factors, lower rates of clinical end points, independently
including blood pressure (BP) itself [4,5] . LVH of the effects of BP lowering and ­t reatment
regression during treatment [6] has translated to modality [12] .

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 Review Janardhanan & Kramer

The calculation of LVM on echo is based on a mathematical Geometric patterns of LV remodeling in hypertension
formula: Different geometric forms of LVH have been adopted to classify
the maladaptive responses of the LV in hypertension [14,17] . LV
LVM = 0.8 (1.04 [(LVIDD + PWTD + IVSD) 3
geometry is classified into four exclusive groups ( Figure 1 ; [18]) on
- (LVIDD) ]) + 0.6g
3
the basis of LVM and RWT: concentric LVH (increased mass
as modified by Devereux et al. using the American Society of and increased RWT), eccentric LVH (increased mass and nor-
Echocardiography convention [13] , where LVIDD is left ventricle mal RWT), concentric remodeling (normal mass and increased
internal dimension in diastole, PWTD is posterior wall thickness RWT) and normal geometry (normal mass and normal RWT).
in diastole and IVSD is intraventricular septal thickness in dias- Concentric hypertrophy carries the highest risk and eccentric
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tole. This modified formula was validated on necropsy findings hypertrophy an intermediate risk, whereas concentric remodeling
in 52 subjects [13] . Table 1 shows previously published cut-off values is associated with a smaller, albeit important risk [19,20] .
for LVH and LVM evaluated by echocardiography and cardiac
magnetic resonance (CMR). Echocardiography to assess LVH in HHD
The prevalence of LVH on echocardiography in hypertensive
Relative wall thickness patients has been reported to be approximately 40% [21,22] . Both
Relative wall thickness (RWT) is measured in clinical studies as: M-mode (Figure 2) and 2D echocardiography are used in the meas-
urement of LVM. M-mode echocardio­graphy has the advantage of
(IVSD + PWTD) superior endocardial definition, as the high frame rate improves
LVIDD
the spatial resolution. M-mode echocardio­graphy was the first
The reference cut-off value for increased RWT derived from echo method to be validated and it is relatively simple and quick.
upper limits of normal samples is usually 0.45 [14] . RWT pro- The M-mode method measures the left ventricle (LV) in one
vides information regarding LV geometry independent of other dimension and assumes a prolate ellipsoid shape for the LV with
calculations [15] , precluding the requirement of most corrections. a ratio of long:short axis lengths of 2:1. The M-mode method
LV geometry as evaluated by RWT may provide an independ- will detect all but the mildest degrees of LVH.
For personal use only.

ent stratification of LV systolic and diastolic functions in essen- However, the accuracy and reproducibility of M-mode
tial hypertension [15] . Measurements of LV mass and RWT are echocardio­graphy at measuring LVM has been debated. There
prognostically important in the hypertensive patients without is a potential for variations in measured wall thickness, depending
LVH. In the Losartan Intervention For Endpoint Reduction in on the ultrasound beam angle to the LV wall and the assumption
Hypertension (LIFE) study, patients with inappropriately high that the wall thickness is uniform throughout the LV. In addi-
but nonhypertrophic LV mass had a higher RWT and BMI. It tion, the assumed prolate ellipsoid shape of the LV is no longer
was observed that inappropriately high LV mass was associated valid in patients with LVH [23] . Furthermore, LVM as measured
with relevant, often preclinical, manifestations of cardiac dis- by M-mode echocardio­graphy relies on linear measurements of
ease in the absence of traditionally defined echocardiographic wall thickness [12] , which, when cubed, increase the standard
LV hypertrophy and concentric geometry [16] . deviation (SD) by a factor of 2–3. As elevated LVM is defined
as mean +2 SD, M-mode echocardiography has the potential to
underestimate the prevalence of LVH in hypertensive cohorts
(Table 1) [24,25] .
Two dimensional echocardiography (Figure 3) is thought to be
more accurate and reproducible than the M-mode method [26] ,
and is now more commonly used for LVM measurements. 2D
echocardiography relies on mathematical formulae to estimate the
LVM but there is no cube function in these formulae and hence
Concentric remodeling Concentric LVH measurement errors are not magnified. However, it still assumes a
prolate ellipsoid shape of the LV and a uniform LV wall thickness.

3D echocardiography for LVH assessment

3D echocardiography has improved the intra- and inter-observer
variability of the LVM measurements compared with M-mode
and 2D echocardiography [27] , with its accuracy reported to be
Normal Eccentric LVH close to that of CMR [28] . Quantification of LVM using real-time
3D echocardiography is highly reproducible and correlates well
Figure 1. Classification of left ventricular geometry on the with CMR [29] . In contrast to M-mode and 2D echocardiography,
basis of left ventricular mass and relative wall thickness. 3D echocardiography does not rely on geometrical assumptions
LVH: Left ventricular hypertrophy. for calculating LVM [29] . The second-generation real-time 3D
Adapted with permission from [18] . technology that offers second-generation matrix array probes with

200 Expert Rev. Cardiovasc. Ther. 9(2), (2011)

 Imaging in hypertensive heart disease Review

3000 simultaneously active ultrasound ele-

ments has solved the acquisition difficulties,
while advances in computer technology and
ana­lysis software have shortened the dura-
tion of postprocessing [30] . However, supe-
rior-quality 3D images are still dependent
on optimal echo windows and up to a third
of patients have suboptimal echo windows
for this purpose.
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CMR for LVH assessment

As discussed previously, the cubing of the
measurements for LV wall thickness when
using M-mode echocardiography amplifies
any errors of such measurements, resulting
in a significant variation of LVM estimates
compared with direct measurement using
techniques such as CMR [31,32] . CMR has
been demon­strated to be more reproduc-
ible than either M-mode or 2D echocardio­ Figure 2. Marked left ventricular hypertrophy noted on 2D-guided
graphy measurements [32–34] for the estima- M-mode echo.
tion of LVM [35,36] . It provides a spatially
defined 3D dataset at multiple levels throughout the heart, and relatively high observer and interstudy variability [41] . CMR or 3D
hence the measurement of LVM does not require geometric echocardiography should be the techniques of choice in clinical
For personal use only.

assumptions about the shape of the LV. CMR has been validated trials investigating LVM regression where the accuracy of LVM
in animal studies [37–39] and the excellent contrast between blood, measurements will allow for the accurate detection of small degrees
and myocardial tissue and the high spatial resolution means of change in LVM in smaller cohorts of patients, particularly when
that the endocardial and epicardial contours are easily defined. recruitment of large numbers of patients is not possible.
Presently, the methodology of choice for measuring LVM by Cardiac magnetic resonance can also demonstrate parallel
CMR is steady-state free precession (SSFP) cine imaging (Figure 4) . reductions in LV mass and chamber volume with normalization
The absolute values of LVM measured by CMR tend to be lower of LV ejection fraction during a relatively brief period of improved
than those for echocardiography (Table 1) because SSFP cine imag- BP control with multiple agents that interrupt the hypertrophic
ing allows the visualization of myocardial trabeculae and thus stimuli from the RAAS. Particularly notable is the short dura-
includes trabeculae in the LV volume measurement excluding it tion of treatment required to detect such changes using a highly
from the mass. Echocardiography, however, generally includes reproducible method such as CMR [42,43] . Echocardiographic
trabeculation in the measurement of LV mass. Although CMR studies of LVH regression have typically required longer treatment
has excellent reproducibility for measuring LVM and is widely periods to demonstrate LVH regression as well as larger sample
perceived as the gold standard, its accuracy has not been validated sizes. Table 2 lists the advantages and disadvantages of the various
against necropsy LV weight in humans. methods currently available to assess LVH.

Implications for clinical trials

Echocardiography has been successfully A B
used in large clinical trials and has pro-
vided a wealth of knowledge in patients
with hypertensive LVH [12,40] . Although
2D echocardiographic determination of
LVM is useful in identifying patients with
severe LVH, its high measurement vari-
ability impairs its value in the subgroup of
hypertensive patients with milder concen-
tric and/or eccentric LVH, and in those
with concentric remodeling. Demonstration
of LVM regression using M-mode or 2D
echocardiographic methods requires rela- Figure 3. Left ventricular hypertrophy on 2D echo. (A) Parasternal long-axis view.
tively large cohorts of patients because of the (B) Parasternal short-axis view.

www.expert-reviews.com 201
 Review Janardhanan & Kramer

Harmonic Phase imaging [51] has enabled the use of this technique
in large epidemiologic studies such as the Multi-Ethnic Study of
Atherosclerosis (MESA). In this cohort study designed to investigate
the nature of atherosclerosis in asymptomatic individuals, a total
of 1184 participants (aged 45–84 years) underwent tagged CMR.
Regional LV function was quantified by analyzing peak systolic cir-
cumferential strain (Ecc). Higher diastolic BP (DBP) was associated
with lower Ecc (p ≤ 0.002). The study concluded that higher DBP
and smoking are associated with decreased regional LV function
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in asymptomatic individuals [52] . The association between reduced

regional LV function and higher DBP was substantially attenuated
after controlling for LV mass, underscoring the importance of LVH
in the development of regional LV dysfunction.

Diastolic dysfunction in HHD

Diastolic dysfunction is one of the earliest manifestations of
HHD. It refers to abnormalities in the mechanical properties of
the heart, such as decreased diastolic distensibility, slowed fill-
ing or relaxation of the LV – regardless of whether the LVEF is
normal or abnormal, and whether the patient is symptomatic or
asymptomatic [53,54] . Diastolic dysfunction is estimated to affect
approximately 50% of hypertensive patients in the community [55]
and correlates with the development of LVH [56,57] . Patients with
Figure 4. Four-chamber long-axis view on an end-diastolic longstanding hypertension are at increased risk for developing
For personal use only.

frame from a steady-state free precession cine image set LVH-associated abnormalities of myocardial relaxation, which
demonstrating left ventricular hypertrophy by cardiac
magnetic resonance.
contribute to abnormal LV filling in diastole and elevated intrac-
ardiac filling pressures [57] .
As discussed previously, the prediction of cardiovascular mor-
Assessment of intramyocardial function in HHD bidity and mortality in hypertensive individuals may be independ-
Intramyocardial strain is a complex marker of the effect of hyper- ent of BP itself [58] . The abnormal compliance of the LV with
trophy on myocardial mechanics. In hypertrophy, changes in gene increased filling pressures for a given volume and higher incidence
expression, contractile protein kinetics, calcium handling and of subendocardial ischemia with associated diastolic dysfunction
metabolism all occur and might contribute to reduced myocardial are a few of the many postulated mechanisms for the deleterious
deformation, which initially may be adaptive. However, over the effects of LVH.
longer term it may affect global myocardial performance and
prognosis. LV midwall shortening (MWS), an indirect measure Importance of imaging diastolic function in HHD
of myocardial performance assessed by transthoracic echocardio­ Adequate control of arterial pressure in hypertensive patients
graphy, is decreased in a subset of patients with hypertensive should favorably alter loading conditions in the short term, while,
LVH [44] . These patients are at increased risk for cardiovascular in the long term promote regression of hypertrophy. Diastolic
events despite normal endocardial fractional shortening [45] . dysfunction in HHD improves as LVH regresses [59] . Interestingly,
Echocardiographic calculation of MWS is a geometry-based abnormalities of diastolic function can also be detected by sensi-
index derived from linear measurements of the posterior and the tive imaging techniques in the absence of LVH, thus suggesting
septal walls, and consequently cannot distinguish between septal that these abnormalities could precede or develop independently
versus posterior wall function. Thus, whether depressed MWS of LVH. The benefits of LVH regression in hypertensive indi-
represents global or regional intrinsic depression of LV myocardial viduals appear to be independent of and additive to the effects
function in pressure-overload hypertrophy is unknown. Previous of BP lowering [12] , suggesting that the improvement in diastolic
experiments demonstrated that increased LV pressure could have dysfunction with LVH regression may play a role.
dissimilar effects on regional LV wall stress because of different
radii of curvature, resulting in regional mechanical heterogeneity Echocardiography for diastolic dysfunction
caused by dissimilar afterload [46] . Generally, in early hypertension there is delayed relaxation of the
Cardiac magnetic resonance tissue tagging allows intramyo­cardial myocardium because of hypertrophy and mild degrees of stiffen-
displacement and strain to be measured noninvasively by monitor- ing, affecting the peak early filling (E-wave) and late diastolic
ing motion of identifiable material points distributed throughout filling (A-wave) velocities of the mitral valve inflow, manifested
the myocardium [47–49] . MWS is depressed in hypertensive LVH as a reduced E/A ratio. In severe, long-standing hypertension, the
as demonstrated by CMR myocardial tagging [50] . The advent of LV can develop systolic dysfunction as well. At this point, there

202 Expert Rev. Cardiovasc. Ther. 9(2), (2011)

 Imaging in hypertensive heart disease Review

may be evidence of more advanced diastolic dysfunction with a

normal or high E/A ratio, representing pseudo-normal filling or
a restrictive physiology.
Until recently, the most widely accepted and utilized method to
assess LV diastolic function noninvasively has been assessment of
transmitral inflow or pulmonary venous flows utilizing Doppler
echocardiography [60,61] . Neither of these techniques evaluate LV
relaxation directly. Instead, they measure the impact of altered LV
diastolic properties by assessing diastolic flow velocities that result
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from pressure gradient changes at the mitral orifice, and systolic

and diastolic flow velocities in the pulmonary veins, respectively.
These conventional Doppler assessments are very much load-
dependent, and as such can change dramatically due to small
alterations in heart rate or ventricular preload [62,63] .
Tissue Doppler imaging (TDI) is a relatively new technique
that allows direct quantification of mitral annular velocities. TDI
can measure early diastolic mitral annular velocity (Ea), and a
late (atrial contraction) diastolic mitral annular velocity (Am)
(Figure 5) [64] . Nagueh et al. and others have reported that, although
transmitral Doppler E-wave velocity is altered by changes in Figure 6. Tissue Doppler imaging in a patient with
preload or left atrial pressures [65] , Ea at the lateral left ventricu- hypertension demonstrating reduced early diastolic mitral
annular velocity (Ea), suggestive of diastolic dysfunction.
lar base does not change significantly, and effects of preload can
be corrected by a ratio of E/Ea [66] .
global e [69] . These data suggest that velocity abnormalities occur
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Strain & strain rate relatively early in hypertensive subjects, are associated with (or
These measures provide a more detailed characterization of myo- even responsible for) diastolic filling abnormalities, and thus may
cardial mechanics and may reveal subclinical abnormalities earlier be a target for preventive strategies [70] .
in HHD than is apparent by the detection of LVH or overt DD. It
should be emphasized that reduced strain and strain rate, which is CMR for diastolic dysfunction
a sensitive marker for preclinical HHD, are nonspecific and have There is homology between CMR and transthoracic echo­
also been reported in preclinical infiltrative and hypertrophic cardiography for the assessment of diastolic inflow, with excellent
cardiomyopathy, and are likely to be present in a broad range of agreement of quantitative velocity measurements [71] . Diastolic
other disease states as well. Thus, strain and strain rate data must blood flow assessment by CMR can be performed in a single scan,
be put in context of the clinical situation. either in a single breath-hold or averaged over approximately 3 min.
This can be part of a routine CMR examinations, either as an
2D-speckle imaging adjunctive test when evaluating systolic function or even as a pri-
Newer methods, such as 2D-speckle imaging, appear to provide a mary test when echocardiographic data cannot be obtained. Thus,
direct angle- and geometry-independent measure of circumferen- CMR has a demonstrated potential to define diastolic function and
tial strain (e) [67] . A principal advantage of speckle tracking imaging quantify its properties in terms of active and passive stages, and its
is that it offers measurements of strain that,
unlike tissue Doppler, are not dependent on Table 1. Accepted criteria and cut-off values for left ventricular
insonation angle. Amundsen et al. showed a hypertrophy and left ventricular mass by currently available
good correlation between longitudinal 2D imaging techniques.
strain values and those obtained by CMR
tagging [68] . This method permits measure- Imaging technique Male g/m2 Female g/m2
ment of the three principal systolic strains: Echocardiography
circumferential, longitudinal and radial. M-mode LVM indexed BSA >125 >110
Narayanan et  al. noted that HHD with
2D echo LVM indexed BSA >102 >88
normal ejection fraction is associated with
reduced myocardial velocities and reduced Cardiac magnetic resonance
regional function but normal global systo- TGE LVM indexed BSA >96 >77
lic strain (e) [69] . Velocity abnormalities
SSFP indexed BSA >83 >67
occur early in hypertension and may be an
BSA: Body surface area; LVH: Left ventricular hypertrophy; LVM: Left ventricular mass; SSFP: Steady-state
appropriate target for preventive strategies free precession; TGE: Turbo gradient echo.
because they occur before abnormalities in Modified from [25].

www.expert-reviews.com 203
 Review Janardhanan & Kramer

recognizing that slightly less than half of patients may have suit-
Table 2. Advantages and disadvantages of the
able backscatter signal for ana­lysis [77] . A more robust approach for
various methods currently available to assess left
visualization of myocardial fibrosis is late gadolinium enhancement
ventricular hypertrophy.
(LGE)-CMR (Figure 6) [78] .
Measure ECG M-Mode 2D echo 3D echo CMR This technique shows enhancement in regions of fibrosis with
Cost + ++ ++ ++ +++ appropriate T1-weighted techniques 10–15 min after intravenous
Sensitivity + ++ ++ +++ +++
administration of gadolinium-based contrast because of:
• Expanded extravascular volume in fibrotic myocardium that is
Specificity +++ +++ +++ +++ +++
occupied by this extracellular contrast agent;
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Availability +++ +++ +++ + +

• Impaired efflux of gadolinium-based contrast due to vascular
Complexity + + ++ ++ ++
changes in fibrotic myocardium.
+: Low; ++: Moderate; +++: High; CMR: Cardiac magnetic resonance.
Modified from [25]. A recent study showed that approximately half of patients with
LV hyper­trophy due to arterial hypertension manifested patchy
relaxation and compliance characteristics. CMR is also useful for enhancement on LGE imaging [79] ; this pattern is clearly dis-
assessing inflow and myocardial velocities, and revealing proper- tinguishable from the subendocardial enhancement of infarcted
ties of the chamber and myocardium [72] , thus providing insights myocardium. Raman et al. have shown that severity of diastolic
not fully available with other invasive and noninvasive strategies. dysfunction increases with extent of fibrosis by LGE [80] .
Visibly enhanced myocardial regions by LGE-CMR may be
Myocardial fibrosis absent in HHD even in the presence of diffuse interstitial fibrosis.
A common end point of many cellular and noncellular pathologic A critical drawback to the technique of LGE-CMR in the detec-
processes in HHD is myocardial fibrosis. Fibrosis quantification in tion of more diffuse myocardial fibrosis is that it is qualitative,
endomyocardial samples obtained via transjugular biopsy showed a not quantitative, and it relies on the difference in signal intensity
significantly greater collagen volume fraction in patients with hyper- between scarred and normal adjacent myocardium to generate
For personal use only.

tension than in normotensive controls [73] . Myocardial fibrosis in image contrast. Because collagen deposition in LVH is commonly
animals is associated with worsening ventricular systolic function, diffuse, the technique of delayed contrast enhancement often
abnormal cardiac remodeling and increased ventricular stiffness [74] . shows no regional scarring.
The link between collagen turnover and myo­cardial fibrosis is not This has prompted the development of the technique of T1
fully understood, but it is thought to play an important role in the mapping by which quantification of global T1 time can help to
development of diastolic dysfunction [75,76] . quantify diffuse myocardial fibrosis. These studies are in the early
phases of technique development and application. T1 mapping
Imaging myocardial fibrosis may be applied to the entire myocardium allowing quantification
Various imaging techniques have emerged to quantify myocar- of differences in T1 relaxation, an intrinsic property of spins or
dial fibrosis noninvasively. Echocardiography with integrated protons in fibrotic versus normal myocardium. These differences
backscatter show good correlation with collagen volume fraction, are further exaggerated after gadolinium administration, which
showed good correlation with collagen volume fraction in a small
study of post-orthotopic heart transplant patients by Iles et al. [81] .
Their data demonstrated profound differences in myocardial con-
trast accumulation between normal and heart failure subjects
utilizing post-contrast T1 mapping, with histologic data support-
ing their assertion that these changes reflect diffuse fibrosis. The
differences also correlated with echocardiographic measurements
of diastolic function, indicating shortening of T1 time may reflect
altered diastolic function as a functional consequence of myo­
cardial fibrosis. T1 mapping has the potential to be an end point
in future therapeutic trials targeting fibrosis in HHD, eliminating
the need for serial invasive endomyocardial biopsies [82] .

Ischemia in HHD
In hypertensive patients, coronary arterial insufficiency may
occur as a consequence of increased coronary arterial resist-
Figure 6. Late gadolinium enhancement–cardiac magnetic ance, including diminished coronary flow and flow reserve, and
resonance in a patient with hypertensive left ventricular altered blood rheology. These changes in the coronary circulation
hypertrophy demonstrating a mid-wall region of late are independent of occlusive atherosclerotic epicardial arterial
gadolinium enhancement in the inferoseptum. disease. Diminished coronary flow and flow reserve, increased

204 Expert Rev. Cardiovasc. Ther. 9(2), (2011)

 Imaging in hypertensive heart disease Review

coronary vascular resistance and blood viscosity in hypertension, provide useful information in patients with suboptimal echo win-
and the increased myocardial oxygen demand engendered by dows. It must be noted that at the present time, there is limited
the elevated arterial pressure and increased cardiac mass all play data available on CMR techniques such as T1 mapping and LGE
a major part in the high prevalence of sudden death and silent in hypertensive LVH. The relative expense of CMR precludes
ischemia associated with hypertension. Abnormalities in the its routine use in patients with hypertensive LVH, but for clini-
coronary micro­circulation that accompany cardiac hypertrophy cal trials of LVH and LV mass reduction with antihypertensive
play a significant role in the pathogenesis of the complications therapy, CMR or 3D echocardiography should be the imaging
associated with LVH [83] . modality of choice.
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Imaging for ischemia in HHD Expert commentary

Myocardial perfusion scintigraphy may be valuable and could In spite of advances in therapies, the hypertensive patient’s risk
have a potential role in the detection of diminished coronary of heart failure has changed little since its recognition by large
flow and flow reserve in HHD. However, there are issues with the population-based studies over the past decades. Hypertensive
technique in this patient population. Since myocardial thallium LVH is an established predictor of cardiovascular events in hyper-
uptake is dependent on regional Na + –K+ pump function, and tension. Since a normal ECG does not exclude the presence of
technetium uptake is dependent on myocardial blood flow, any LVH, imaging is important for diagnosis and prognostication in
myocardial pathology may produce an abnormal image. It may HHD. 2D echocardiography still remains the imaging technique
thus be postulated that hypertensive patients, especially those of choice for the initial assessment of HHD. However, advanced
with LVH, may have perfusion abnormalities unrelated to epicar- echocardiographic tools (including 3D echocardio­graphy) and
dial coronary artery disease that serve to alter the kinetics of radio- CMR techniques offer a more comprehensive assessment of
isotope tracer agent and result in abnormal images interpreted as HHD, although they are limited by inadequate acoustic windows
representing ischemia or infarction [84] . In HHD, Picano et al. in a third of patients and cost, respectively. The newer real-time
have shown that ST segment depression and/or myocardial per- 3D echocardiographic technology now offers second-generation
fusion abnormalities are frequently found with angiographically matrix array probes, solving the acquisition difficulties, while
For personal use only.

normal coronary arteries associated with LVH and/or microvas- advances in computer technology and ana­lysis software have
cular disease [85] . Although stress echocardiography tends to have shortened the duration of postprocessing. CMR is a reliable means
a higher specificity in HHD for angiographically proven epicar- of evaluating cardiac morphology, and therefore well suited for
dial CAD [85] , the sensitivity of wall motion abnormalities for identifying and characterizing hypertensive patients with LVH
detection of ischemia is markedly reduced in the presence of LVH. and accurately measuring LV mass. Such precise measurements
Microvascular disease as a cause of endothelial dysfunction has of LV mass using CMR or 3D echocardiography allows a smaller
been proposed as one of the etiologies of chest pain and myocardial sample size to detect changes in clinical trials of LVH regression
ischemia in patients with hypertension and/or diabetes and normal on hypertensive therapy.
coronary arteries on angiography [86] . Patients with positive stress
testing for coronary ischemia and exclusion of significant coronary Five-year view
stenosis invasively were found to have subendocardial perfusion Advances in imaging have provided tools for comprehensive
deficits on stress perfusion CMR [87] . Stress perfusion CMR allows noninvasive imaging of LVH, diastolic dysfunction, myocardial
noninvasive differentiation between patients with significant steno- fibrosis and ischemia observed in HHD. The currently available
sis and patients with micro­vascular disease caused by hypertension echocardiographic techniques such as TDI, strain, strain rate and
and/or diabetes based on the temporal and spatial extent of per- speckled tracking will continue to evolve and become more routine
fusion deficits. Patients with microvascular disease more often have and user friendly in the years ahead. 2D-speckle imaging appears
diffuse perfusion deficits with shorter persistence than patients to provides a direct angle- and geometry-independent measure
with significant epicardial coronary artery disease [88] . of circumferential strain. Advances in understanding myocardial
mechanics in hypertension, coupled with targeted therapies, sug-
Clinical applications of imaging HHD gest that routine clinical application of these advanced echocar-
In clinical practice the ECG is usually the first test performed to diographic methods could benefit patients in the detection of
assess for the presence of LVH. Although LVH on ECG has the subclinical disease, quantification of myocardial tissue dynam-
potential to identify the subgroup of patients with the highest ics, and tracking changes in disease progression or in response to
LVM and the highest risk [89,90] , false positives are very common hypertensive therapies. Since diastolic dysfunction often precedes
in the young and in patients of African–American origin. In addi- the development of LVH, these techniques will help early detection
tion, a normal ECG does not exclude the presence of LVH  [91] , of diastolic dysfunction in the absence of LVH.
and these patients should be evaluated further with imaging. Cardiac magnetic resonance has demonstrated great poten-
Echocardiography is the preferred initial imaging strategy since tial to define diastolic function in terms of active and passive
it can confirm the presence of LVH as well as provide additional stages, and its relaxation and compliance characteristics. In the
information such as LV systolic/diastolic function and the pres- future, CMR is likely to utilized more often in HHD to assess
ence or absence of other potential causes of LVH. CMR can inflow and myocardial velocities, and revealing properties of the

www.expert-reviews.com 205
 Review Janardhanan & Kramer

LV, thus providing insights not fully available via other invasive Financial & competing interests disclosure
and noninvasive strategies. Imaging fibrosis may improve the Christopher M Kramer receives research equipment support from Siemens
understanding of the pathophysiology of HHD. Novel CMR Healthcare. The authors have no other relevant affiliations or financial
methods, such as T1 mapping, could become established as a involvement with any organization or entity with a financial interest in or
tool for non­invasive quantification of diffuse myocardial fibrosis financial conflict with the subject matter or materials discussed in the manu-
in LVH, which could be used to evaluate newer therapies aimed script apart from those disclosed.
at reducing myocardial fibrosis. No writing assistance was utilized in the production of this manuscript.

Key issues
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Washington University Library on 01/01/15

• Hypertensive left ventricular hypertrophy (LVH) represents a powerful predictor for cardiovascular morbidity and mortality, independent
of other cardiovascular risk factors, even blood pressure itself.
• A normal ECG does not exclude the presence of LVH, and therefore patients should be evaluated further with imaging.
• Echocardiography is clinically useful in the detection of LVH and the assessment of diastolic function.
• Cardiac magnetic resonance (CMR) has been demonstrated to be more accurate and reproducible for the estimation of left ventricular
(LV) mass.
• Precise measurement of LV mass using CMR or 3D echocardiography allows a smaller sample size to detect changes in clinical trials.
• Myocardial fibrosis, a common end point in hypertensive heart disease (HHD), has been linked to the development of LVH and
diastolic dysfunction.
• Recent developments in CMR techniques, such as T1 mapping, can help us quantify diffuse fibrosis that occurs in HHD.
• Noninvasive quantification of diffuse myocardial fibrosis in LVH is highly desirable in evaluating newer therapies aimed at reducing
myocardial fibrosis.

5 Verdecchia P, Schillaci G, Borgioni C et al. fibrillation: population-based

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