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: drddyang@163.com

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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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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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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