REVIEW PAPER
Electrical Inhomogeneity in Left Ventricular Hypertrophy
Changzhao Gao • Dandan Yang
� Springer Science+Business Media New York 2014
Abstract Recent studies designed to assess the relation-
ship between aortic compliance and heterogeneity of heart
electrical activity has shown that hypertrophy aggravates
repolarization disturbances in the myocardium. Numerous
mechanisms of electrical instability and inhomogeneity
associated with left ventricular hypertrophy are now under
investigation. Most of the studies have been found to be
focused on ventricular Gradient, QT dispersion, amplitudes
of isointegral maps during ventricular repolarization,
abnormally low-QRST areas, dispersion of the QT interval,
and spatial QRS-Tangle. These studies point to marked
repolarization abnormalities in left ventricular hypertrophy
and the dispersion of the QT interval as a valuable index
for inhomogeneity of repolarization and the subsequent
heart rate variability. The heart rate-corrected QT disper-
sion and QT apex dispersion seem to be significantly
longer in the patients with left ventricular hypertrophy than
in normal individuals. The review study has also identified
QRST isointegral map as a valuable technique in assess-
ment of the electro-cardiac events in LVH.
Keywords LVH � Electrical heterogeneity � T-wave
abnormality � Secondary S-T segment vector � Primary
T-wave abnormality
Introduction
Left ventricular hypertrophy (LVH) can be defined as the
thickening of the myocardium in the left ventricle of the
heart. LVH is an important predictor of adverse cardiovas-
cular outcomes in hypertension patients and a potential risk
factor for stroke, heart failure, coronary heart disease, and
sudden death [1–3]. The most intriguing part of the LVH is
the adverse changes it brings about in the myocardial tissue.
These adverse myocardial changes bring about deleterious
physiological alterations resulting in the formation of an
arrhythmogenic myocardial substrate causing serious elec-
tric heterogeneity and electrical instability. Since, the
mechanical functioning of the human heart depends on the
normal electrical function of the cardiac muscles [4, 5],
changes in the characteristics or the functions of these
myocardial ionic or electric events lead to various life
threatening cardiac dysfunctions. The current review is an
appraisal the mechanisms of electrical instability and inho-
mogeneity associated with LVH as evidenced by publica-
tions in the last 15 years on the mechanisms of electrical
instability and inhomogeneity associated with LVH.
Study Selection
PubMed and PMC were searched for studies pertaining to
the electric heterogeneity in LVH, electrocardiographical
studies designed to assess the relationship between aortic
compliance and heterogeneity of heart electrical activity.
The search terms included electric heterogeneity in LVH,
The T-wave abnormality, secondary S-T segment vector,
primary T-wave abnormality, QT dispersion, ST depres-
sion, and T-wave pattern abnormalities. The Initial Search
brought forth 398 Studies of which 250 studies excluded as
not pertaining specifically to electrical inhomogeneity
C. Gao
Department of Clinical Medicine, School of Clinical Medicine,
Jilin University, Changchun, Jilin, People’s Republic of China
D. Yang (&)
Department of Regeneration Medicine, School of
Pharmaceutical, Jilin University, Changchun, Jilin, People’s
Republic of China
e-mail: [email protected]
123
Cell Biochem Biophys
DOI 10.1007/s12013-014-9850-6
(62.81 %). One hundred and forty eight studies were
included as relevant to electrical inhomogeneity (37.19 %)
and 48 Studies included as more relevant to electrical
inhomogeneity of heart (12.06 %). Out of these, 21 studies
were finally selected for review as relevant to electrical
inhomogeneity in LVH (5.28 %). The search results were
ascertained by a second reviewer for accuracy.
Analysis
‘‘The Cochrane Reviewers’ Handbook’’ [6] suggests that any
healthcare review should be a clearly defined, focused
review that begins with a well-framed objective that would
specify the types of population, interventions, and outcomes
of interest. These review guidelines also suggest that certain
study designs are more appropriate for answering specific
objectives and the authors should select study designs that
are likely to provide reliable data that address the objective of
the review. It is an agreed fact that nonrandomized studies
produce effect estimates that indicate more extreme benefits
of the effects of health care than randomized trials and thus,
including studies other than randomized trials in a review
require extra efforts to identify studies and to keep the review
up to date [6]. The EPOC data collection checklist of the
Cochrane Effective Practice and Organization of Care
Review Group to determine the quality of the methodology is
another useful guidance tool for healthcare reviews [6].
The literature review has been based on a five step study
design that includes search for relevant publications in
various data bases available, selection of relevant publi-
cations by application of inclusion and exclusion criteria,
quality assessment of the studies included, data extraction,
and data synthesis. The results and studies in this review
have been summarized in a descriptive and narrative
manner. Quality Assessment has been done with indepen-
dent assessment by two reviewers on quality of the meth-
odology. The differences have been resolved by discussion
with a third reviewer, wherever necessary.
Selection Inclusion Criteria
Selection inclusion criteria included comparative research
design, group protocol for electrical inhomogeneity in
LVH, prevention and control, specific research studies on
electrical inhomogeneity in LVH, and LVH electrical
inhomogeneity awareness among scientific population.
Selection Exclusion Criteria
Selection exclusion criteria included editorials, letters, and
prescription descriptions that are nonspecific to electrical
inhomogeneity in the target population.
Selection Process
Selection Process was done by elimination of the exclusion
criteria and absorption of the inclusion criteria.
Quality Assessment
Quality Assessment was done with assessment by the
researcher on quality of the methodology. There were thus
no differences to be resolved by discussion with the second
or third reviewer. EPOC data collection checklist of the
Cochrane Effective Practice and Organization of Care
Review Group to determine the quality of the methodology
was followed. The results and studies in this review have
been summarized in a descriptive and narrative manner.
Quality Assessment has been done with independent
assessment by two reviewers on quality of the methodol-
ogy. The differences have been resolved by discussion with
a third reviewer, wherever necessary. Specific findings on
the ventricular Gradient, QT dispersion, amplitudes of
isointegral maps during ventricular repolarization, abnor-
mally low-QRST areas, dispersion of the QT interval, and
spatial QRS-Tangle have been taken into account.
Results
The review has brought forth numerous mechanisms of
electrical instability and inhomogeneity associated with
LVH. Most of the studies have been found to be focused on
Ventricular Gradient, QT dispersion, amplitudes of isoin-
tegral maps during ventricular repolarization, abnormally
low-QRST areas, dispersion of the QT interval, and spatial
QRS-Tangle. Specific studies pertaining to T-wave abnor-
mality, ST depression, repolarization disturbances in the
myocardium due to LVH, T-wave pattern abnormalities,
features of LVH diagnosed electrocardiographically by the
Sokolow-Lyon index or the Cornell product criteria,
quantification of ventricular depolarization and repolari-
zation employing VCG and QRST isointegral map tech-
niques have also been identified.
On T-wave Abnormality in LVH
Willis Hurst [7] has elucidated the T-wave abnormality
often referred to as secondary T-wave abnormality as the
one observed when the mean spatial T vector becomes
180� away from the mean spatial QRS vector and the
spatial ventricular time gradient becomes zero. The mean
spatial S-T segment vector is directed parallel with the
mean spatial T vector and is referred to as a secondary S-T
segment vector. Willis Hurst [7] is also of the opinion that
when the ventricular time gradient is directed abnormally,
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123
it should be assumed and concluded that there are two
abnormalities of repolarization, the one caused by LVH
and the other due to ischemia or other cardiac conditions.
This abnormality is often referred to as a primary T-wave
abnormality [5, 7]. Zapolski et al. [8] and Wilson et al. [9]
have classified several data processing methods that are
being proposed to detect the T wave abnormalities and
shown that new T-wave morphology interpretations can be
utilized as reliable measures of repolarization heterogene-
ity. They have also demonstrated that the heterogeneity of
ventricular repolarization can be measured by calculating
the relative T-wave residuum (TWR). The relative TWR
has been found to be more reliable than conventional
electrocardiographic indices of ventricular repolarization
including corrected QT, corrected QT dispersion, and
various T-wave morphology indices [8, 10]. Przewłocka-
Kosmala and Kosmala [11] have also shown that there are
enough evidences to point out that an increased QT dis-
persion (QTd) indicates electrical inhomogeneity in the
myocardium leading to ventricular arrhythmias. They have
also elucidated an increased QTd in LVH patients and the
geometry of the tissue in LVH has been shown to have a
positive correlation with the QTd. QTd is calculated as a
difference between the longest QT and shortest QT from
the 12-leads of the standard electrocardiogram [11, 12].
On P-wave Abnormality in LVH
Dagli et.al [13]—in a study to examine whether PD and
P(max) can be used as a noninvasive marker of LVH and
diastolic dysfunction in a hypertensive population—have
shown that LVH and diastolic dysfunction coupled with
increased left atrium diameter and volume show parallel-
ism in hypertensive cases, and these physiopathological
changes may cause different and heterogeneous atrial
electrical conduction supporting the hypothesis that PD can
be used as a noninvasive marker of target organ damage
(LVH and LV diastolic dysfunction) in the hypertensive
population.
On QRS Complex in LVH
Sakata et.al [14] has elucidated that during the course of
the LVH, the left ventricular wall becomes thicker and
hence, the QRS complexes also become larger that can be
typically seen in leads V1–V6. He has further clarified that
in case of the S wave, the S wave in V1 is deep and in case
of the R wave, the R wave in V4 is high. He has also
elaborated the ST depression that is observed often in leads
V5–V6 and refers to them as strain patterns. It is important
here to refer to Goldman [15] who has also shown that
LVH enhances the ventricular electric forces directed to the
left ventricle that can be clearly seen in lead I as a tall
R-wave and in lead III as a tall S-wave (C2.5 mV). A tall
S-wave can also be seen in precordial leads V1 and V2 and a
tall R-wave in leads V5 and V6 (C3.5 mV). In another study
designed to assess the relationship between aortic compli-
ance and heterogeneity of heart electrical activity, Zapolski
et al. [8] have shown that hypertrophy aggravates repo-
larization disturbances in the myocardium based on a three-
dimensional vectorocardiographic (VCG) monitoring to
assess the QRS-Tangle, Tel, and Taz. The VCG parameters
have been shown to have unfavorable influence of poor
aortic compliance on the electrical activity of the heart in
the study group [8]. It has also been shown that electrical
depolarization disturbances indicate ventricular structural
abnormalities and electrical repolarization disturbances
indicate heterogeneities related to ventricular electrical
instability. A recent study to validate the prognostic value
of computer-derived measurements of the spatial alignment
of ventricular depolarization and repolarization from the
standard 12-lead ECG has shown that spatial QRS-Tangle is
a significant and an independent predictor of cardiovascu-
lar mortality that provides greater prognostic facilitation
when compared to the commonly utilized ECG diagnostic
classifications [16, 17].
On QT Interval in LVH
Research studies have also identified the dispersion of the
QT interval as a valuable index for inhomogeneity of
repolarization and the subsequent heart rate variability. The
heart rate-corrected QT dispersion and QT apex dispersion
have been shown to be quite longer in the patients with
LVH than in normal individuals. Patients with hypertrophy
have been shown to have an abnormally long QT apex
dispersion. It has also been shown that the LVH in
hypertensive cases is associated with inhomogeneity of the
early phase of ventricular repolarization, thus increasing
the susceptibility to reentrant ventricular tachyarrhythmias
[18, 19]. Studies have further shown that quantification of
ventricular depolarization and repolarization has been
easier while employing VCG. This is because of the fact
that in this method it is possible to record and measure the
changes in value and direction of the electrical activity
expressed as a function of the vector at the time. The
development of techniques in VCG that automatically
transform computing ECG has opened more avenues to
conduct extensive research. This includes QRS-Tangle. It is
interesting to note that the spatial QRS-Tangle reflects the
direction of propagation of disturbances of the homoge-
neity ventricular depolarization process. Hence, this
reflects the combined measurement of the electrical activity
of the heart. In various studies on the heterogeneity of heart
electrical activity, a number of other parameters of the
VCG have been elucidated. Studies on the spatial
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orientation of the vector T and the utility of the measure-
ment of spatial QRS-Tangle have gained prominence [1, 8,
17]. Wolk et al. [5] have elucidated that LVH increases
transepicardial dispersion of repolarization in hypertensive
patients and should be read as a differential effect on
QTpeak and QTend dispersion. Hypertensive LVH has
been shown to exert a differential effect on QTpeak and
QTend interval dispersion and the most likely explanation
is that these changes reflect a nonuniform prolongation of
action potential duration across the epicardium, leading to
an increase in transepicardial dispersion of repolarisation.
Another study—to determine the prevalence of LVH and
the left ventricular (LV) geometric patterns in the middle-
aged women population of Tallinn and to assess the rela-
tionship between LV geometry, age, blood pressure, and
LV repolarization duration and inhomogeneity in a random
sample of the population of 482 women aged 35–59—has
shown that a prolonged QT dispersion is a marker of
increased myocardial electrical instability and is associated
with LVH and arterial hypertension [20–22].
Isointegral Maps in LVH
Studies have shown that LVH can increase or decrease the
values of time integrals in QRS or QRST isointegral maps.
Thus, it is possible to study the changes that appear during
repolarization in patients with LVH.
In the recent study, the extrema in QRS, STT, and QRST
isointegral maps of 38 hypertensive patients with LVH has
been analyzed and compared a normal control group. Studies
have found that there were no notable changes during the QRS
complex, but the peak-to-peak values have been found to be
increased with increasing ventricular mass (as in LVH). The
highest maxima and the shallowest minima have been found
in LVH patients. During repolarization (STT isointegral
maps, QRST isointegral maps), LVH patients have been
shown to exhibit the lowest mean extrema (flat maps). Sig-
nificant changes have also been found visible in LVH patients
in STT isointegral maps for minima and peak-to-peak values,
in QRST isointegral maps for maxima and peak-to-peak val-
ues. The studies have found increasing values of time integrals
with increasing left ventricular mass during depolarization,
but decreasing values during repolarization [3, 14, 16]. Pre-
vious studies have also documented the extrema of QRS
complex isointegral maps in relation to echocardiographic
parameters. In one of the recent studies, the diastolic heart
dimensions including the thickness of interventricular septum
(IVSd), LV posterior wall (LVPWd), and LV internal diam-
eter (LVIDd) have been documented in a group of hyperten-
sive patients with LVH. Utilizing the 24-lead system, the
mean QRS isointegral maps as well as isointegral maps of
QRS divided into thirds of equal length (QRS1/3, QRS2/3,
QRS3/3) have been recorded and constructed. Regression
analysis has been used to compare maximum, minimum, and
peak-to-peak values of all isointegral maps with echocardio-
graphic parameters [1, 23].
Studies by Hirai et al. [17] point to QRST isointegral
maps as useful tools to detect repolarization abnormalities.
The utilization of the body surface distribution of abnor-
mally low-QkST areas in LVH patients has brought forth
the relationship of the abnormalities in isointegral map to
the severity of LVH for clinical assessment. These studies
have also detailed the process of construction of the QRST
area departure maps from electrocardiographic (ECG) data
recorded in LVH patients and the simultaneous construc-
tion of the isointegral map from body surface electrocar-
diograms at a sampling interval of 1 ms.
Discussion
The current review of literature on the electric heterogeneity in
LVH takes us to the conclusion that electrical depolarization
disturbances do indicate ventricular structural abnormalities
and electrical repolarization disturbances indicate heteroge-
neities related to ventricular electrical instability. The studies
have also given scope for a lucid summary of the electric
heterogeneity in LVH, where, the mean QRS vector is
directed from -20� to ?90� in the frontal plane and 30� to 50�posteriorly with the duration of the QRS complex at B0.10 s.
The review study points to the fact that although the direction
and size of the ventricular time gradient are normal initially,
the ventricular time gradient becomes shorter than the mean
spatial QRS vector when the mean spatial T vector is directed
about 130� away from the mean spatial QRS vector. Published
sources point to a marked presence of repolarization abnor-
malities in LVH and the dispersion of the QT interval as a
valuable index for inhomogeneity of repolarization and the
subsequent heart rate variability. The heart rate-corrected QT
dispersion and QT apex dispersion seem to be significantly
longer in the patients with LVH than in normal individuals.
Studies also point to the fact that quantification of ventricular
depolarization and repolarization can be easier while
employing VCG.
Innovative Finding
The study has also identified QRST isointegral map as a
valuable technique in assessment of the electro-cardiac
events in LVH. The technique is based on the concept of the
ventricular gradient reported by Wilson et al. [9] and first
introduced by Abildskov et al. [20]. Since isointegral maps
are independent of activation sequence and dependent on
repolarization properties, they serve as valuable tools in
clinical assessment of LVH. In practice, the area where the
QRST area is smaller than normal limits (mean-2 SD) is
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123
designated the ‘‘-2 SD area.’’ The echocardiographic LV
mass is calculated by employing Devereux’s method [4, 17].
Patients with large LV masses have 2 SD areas located over
the left anterior chest or the mid anterior chest and the sum of
QRST area values less than the normal range (IQRST) cor-
relate with LV mass in patients though there may not be
significant correlation between IQRST and the severity of
LVH. QRST isointegral departure maps also provide ECG
evidence of LV mass of patients with AS or AR and of sus-
ceptibility to malignant arrhythmias as suggested by Hirai
et al. [17]. It is imperative to note that Body Surface Mapping
for LVH is based the abnormalities in the ST segment and T
wave caused by abnormal voltage gradients during plateau
and rapid repolarization phases of the action potential. Thus,
the changes in the sequence of repolarization those occur
with and without abnormal voltage gradients also play a role.
These changes contribute to ST segment deviations and are
perhaps independent of the secondary QRS amplitude
changes and of the QRS complex prolongation [18, 19, 24].
Conclusion
These studies point to marked repolarization abnormalities
in LVH and the dispersion of the QT interval as a valuable
index for inhomogeneity of repolarization and the sub-
sequent heart rate variability. The heart rate-corrected QT
dispersion and QT apex dispersion seem to be significantly
longer in the patients with LVH than in normal individuals.
The review study has also identified QRST isointegral map
as a valuable technique in assessment of the electro-cardiac
events in LVH.
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