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Annals of Noninvasive Electrocardiology logoLink to Annals of Noninvasive Electrocardiology
. 2014 Nov 4;19(6):524–533. doi: 10.1111/anec.12223

Left Ventricular Hypertrophy: The Relationship between the Electrocardiogram and Cardiovascular Magnetic Resonance Imaging

Ljuba Bacharova 1,2,✉, Martin Ugander 3
PMCID: PMC6932615  PMID: 25367364

Abstract

Conventional assessment of left ventricular hypertrophy (LVH) using the electrocardiogram (ECG), for example, by the Sokolow–Lyon, Romhilt–Estes or Cornell criteria, have relied on assessing changes in the amplitude and/or duration of the QRS complex of the ECG to quantify LV mass. ECG measures of LV mass have typically been validated by imaging with echocardiography or cardiovascular magnetic resonance imaging (CMR). However, LVH can be the result of diverse etiologies, and LVH is also characterized by pathological changes in myocardial tissue characteristics on the genetic, molecular, cellular, and tissue level beyond a pure increase in the number of otherwise normal cardiomyocytes. For example, slowed conduction velocity through the myocardium, which can be due to diffuse myocardial fibrosis, has been shown to be an important determinant of conventional ECG LVH criteria regardless of LV mass. Myocardial tissue characterization by CMR has emerged to not only quantify LV mass, but also detect and quantify the extent and severity of focal or diffuse myocardial fibrosis, edema, inflammation, myocarditis, fatty replacement, myocardial disarray, and myocardial deposition of amyloid proteins (amyloidosis), glycolipids (Fabry disease), or iron (siderosis). This can be undertaken using CMR techniques including late gadolinium enhancement (LGE), T1 mapping, T2 mapping, T2* mapping, extracellular volume fraction (ECV) mapping, fat/water‐weighted imaging, and diffusion tensor CMR. This review presents an overview of current and emerging concepts regarding the diagnostic possibilities of both ECG and CMR for LVH in an attempt to narrow gaps in our knowledge regarding the ECG diagnosis of LVH.

Keywords: noninvasive techniques, electrocardiography, cardiac MRI

The diagnosis of left ventricular hypertrophy (LVH) in clinical practice is a finding that requires the attention of the clinician. It has been documented that LVH detected by echocardiography or the electrocardiogram (ECG) is a risk factor for cardiac morbidity or mortality which is independent of other known risk factors including blood pressure and left ventricular mass.1, 2, 3

In hypertensive patients, the finding of LVH in a patient has a direct impact on therapy. LVH detected by both echocardiography and ECG define target organ damage, and according to the European Society of Cardiology guidelines4 the presence of target organ damage is a key factor in the management of the hypertensive patient.

It has also been shown that antihypertensive therapy decreases signs of LVH by echocardiography or ECG that are associated with improvement of the clinical status and prognosis of a hypertensive patient,5, 6, 7 and thus the benefit of antihypertensive therapy can be monitored. However, these straightforward statements lead to a number of unanswered questions.

It has repeatedly been documented that the diagnostic performance of the ECG for LVH detection is not satisfactory considering the low sensitivity and varying specificity.8 Furthermore, there are 37 different ECG LVH criteria recommended by the American Heart Association, thus making the status of ECG criteria for LVH a potential source of confusion for the clinician.

The variability of the ECG LVH criteria has in part been attributed to the imprecision of echocardiography as a reference method for estimating left ventricular (LV) mass. Subsequently, cardiovascular magnetic resonance imaging (CMR) has been shown to be a far more precise method for determining LV mass compared to echocardiography.10 Importantly, CMR provides additional possibilities for assessment of myocardial tissue characteristics of relevance for LVH beyond measurement of LV mass alone.

In this review, the diagnostic possibilities of both ECG and CMR for LVH are discussed in an attempt to narrow gaps in our knowledge regarding the ECG diagnosis of LVH. Bridging these gaps is vital in order to elucidate the information necessary to inform clinical management of individual patients.

LEFT VENTRICULAR HYPERTROPHY

LVH is defined as an increased LV mass. However, the increase in LV mass is not the only attribute that is changed in LVH.

A more comprehensive definition of hypertrophy defines hypertrophy as an increase in size of the tissue due to an increase in size of the cells in that tissue without increasing their number, thus differentiating hypertrophy from hyperplasia. Consequently, LVH necessitates that the increase in LV mass is due to the increase in size, not number, of the cardiomyocytes comprising the LV. However, the hypertrophic myocardium also undergoes more complex changes affecting both the cardiomyocytes and the interstitium. These changes may include focal or diffuse fibrosis, inflammation, edema, fatty infiltration, ischemic cellular changes due to the imbalance between increased LV mass and blood supply, or abnormal myocardial deposition of substances, including but not limited to amyloid protein (amyloidosis), glycolipids (Fabry disease), and iron (siderosis). Notably, an additional factor to be considered is the time course of development and progress of the hypertrophic process.11, 12 Furthermore, the increase in mass can differ at the tissue, cellular, subcellular, molecular, and genetic levels. These conditions influence the electrophysiological impulse generation and propagation through the ventricles, and consequently impact the resultant ECG.

ELECTROCARDIOGRAPHY

The ECG records the manifestation of electrical activity of the heart as measured on the body surface. The cardiac electric field generated by the heart depends on both active and passive electrical properties of the heart and torso on the electrical impulse generation and propagation through the myocardium. For the sake of simplicity, the electrical properties of the torso will be not reviewed in further detail here.

LVH is a process of complex rebuilding and remodeling of the LV myocardium, including electrophysiological remodeling. The diagnostic accuracy of the ECG LVH criteria have been evaluated in relation to a reference method, such as echocardiography or CMR, which best estimates the major characteristic of LVH—the increase in LV mass. Evaluation of the accuracy and precision of the ECG criteria for estimating LV mass implies that the ECG is a surrogate method for estimating LV mass. However, this view of the ECG as a method for estimating LV mass is unfortunate considering that the generated electric field in general, and the cardiac electric field in particular, does not depend exclusively on the amount of LV myocardium.

CONVENTIONAL ECG CONCEPTS IN LVH

The principal ECG‐derived diagnostic characteristics for LVH detection include an increased QRS complex amplitude, an increased QRS complex duration, a leftward shift of electrical axis of the QRS in frontal plane, and ST‐segment deviation and T wave changes associated with left ventricular strain.9 Furthermore, more advanced ECG methods based on combined multivariate statistics of measures from the ECG have shown promise in diagnosing LVH.13 In addition to conventional 12‐lead ECG measures of QRS amplitudes and durations, those statistical approaches incorporated measures including, among others, the spatial QRS–T angle from the 12‐lead ECG transformed into a vectorcardiogram, high‐frequency ECG components of the QRS complex, and heart rate variability from 5‐minute long ECG recordings at rest.13 The role of these advanced statistical measures for helping to better understand LVH remains to be explored.

The increased QRS complex amplitude is attributed to the increased extent of the electrical activation front passing through the enlarged LV. The enlarged LV also creates a longer trajectory for the activation front to pass, that is, a longer time required, and sometimes also a slowed conduction velocity through the hypertrophied myocardium. Taken together, these changes contribute to a prolonged QRS complex duration.

CMR in Understanding the ECG in LVH

The ECG LVH criteria were developed using comparative studies which directly or indirectly estimated LV size or mass. The morphology and duration of the QRS complex have been attributed to the globally increased LV mass and/or considerations of the LV wall thickness and LV diameter (concentric or eccentric remodeling and/or dilation). By comparison, CMR provides three‐dimensional coverage of the LV without image quality limitations related to ultrasound transmission, and is thus more accurate in estimating dimensions of the LV compared to echocardiography. Furthermore, CMR can be used to evaluate the three dimensional geometry of the extent of hypertrophy, which can be considerably asymmetric in the setting of hypertrophic cardiomyopathy.14 Taken together, CMR provides highly accurate, precise and reproducible estimates of LV anatomy and mass, and is the in vivo reference standard for measuring LV mass.15, 16, 17, 18 The increased precision has made CMR the preferred method for clinical trials where LV mass is an endpoint. For example, a study seeking to detect a 10‐g reduction in LV mass following a therapeutic intervention with 90% power and P < 0.05 would require a sample size of n = 273 by echocardiography, but only n = 9 by CMR.10

However, even considering the advantages of CMR estimates of LV mass over echocardiography, the discrepancies between ECG LVH criteria and LV mass persist. The correlation coefficients between LV mass index and ECG LVH indices have recently been reported to range between r = −0.02 (P = 0.94) for the Sokolow–Lyon index in women to r = 0.76 (P < 0.001) for the Cornell voltage criteria in men.19

Since the hypertrophied myocardium is pathologically altered in more ways than just increase mass, it is apparent that ECG LVH has to move beyond estimation of LV mass.20 With regards to the physiological basis for generating the ECG, it has been documented that the conduction velocity in the hypertrophied LV myocardium is slower than normal.21, 22, 23 The slowing in conduction velocity is understood to be a determinant of QRS duration prolongation. However, diffuse or regionally slowed conduction velocity in the LV also changes the shape of the activation front and consequently the magnitude and orientation of the depolarization vectors.

Simulation studies have shown that LV mass is not the main and only determinant of QRS voltage.24, 25 In these simulations, QRS amplitude and duration were not proportional to the increase in LV mass. Rather, considerable changes resulted from conduction velocity slowing in the LV, even in the normal sized heart. Slowing the conduction velocity in the LV in combination with anatomical changes in the LV resulted in a spectrum of QRS patterns that have been documented in patients with LVH. These include increased QRS voltage, prolonged QRS duration, left axis deviation, prolonged intrinsicoid deflection (the time from QRS onset to the peak of the R wave), as well as a QRS pattern typical of left bundle branch block. Moreover, slowed conduction velocity has been shown to increase the values of clinically used ECG‐LVH criteria. Specifically, such is the case when applied to the Sokolow–Lyon index and the Cornell criteria in all simulated anatomical types of LVH as well as in the normal sized heart. Interestingly, the Cornell voltage‐duration product, which is recommended as a sensitive ECG marker of increased LV mass showed negligible association with the increase in LV mass and/or type of hypertrophy. On the contrary, it was slowed conduction velocity that resulted in an increase in Cornell voltage‐duration product in the reference heart as well as in all simulated anatomical types of LVH. These simulation results indicate that the clinical ECG‐LVH criteria, especially the Cornell voltage‐duration product, more so reflect changes in the electrical properties of the hypertrophied myocardium than an increase in LV mass per se.

Furthermore, regional slowing of conduction velocity in the LV has been shown to lead to changes in the QRS amplitude and morphology consistent with ECG LVH criteria. A slower conduction velocity in the anteroseptal region of the LV resulted in QRS complex changes that are analogous to diagnostic ECG LVH criteria or QRS patterns frequently seen in patients with LVH; namely an increase in RI, SIII, and aVL amplitudes, that is, in leads that create basis for the limb lead QRS voltage criteria.26, 27, 28 The increased R wave in aVL is a component of both the Cornell voltage criteria29 and the Cornell voltage‐duration product.30 Slowing in the anteroseptal region affected four of six components of the Romhilt–Estes score31: R and S amplitude in limb leads, left axis deviation, prolongation of the QRS complex, and intrinsicoid deflection prolongation. Theoretically, slowed conduction could account for a total of seven points in the Romhilt–Estes score, thus exceeding the cutoff value of five points for defining LVH. Additionally, the shift of electrical axis to the left and the presence of a small Q wave in aVL results in a QRS pattern of left anterior fascicular block, which is an ECG finding frequently seen in patients with LVH.

Taken together, both diffuse and focally slowed conduction velocities in the LV myocardium resulted either in an increased QRS voltage or in QRS patterns consistent with ECG findings in LVH, despite an unchanged LV size or mass.

CMR Assessment of LVH Beyond LV Mass

In clinical practice, direct in vivo measurement of conduction velocity is not possible. However, CMR can be used to detect and characterize a number of myocardial pathologies which may affect conduction velocity to varying extents. Such myocardial pathologies detectable by CMR include focal scarring of either ischemic or nonischemic origin,32, 33, 34 diffuse fibrosis,35 edema,36, 37 inflammation,38 fatty infiltration,39 or abnormal myocardial deposition of substances such as amyloid protein,40, 41, 42 glycolipids,43 and iron.44, 45 As mentioned above, the increased mass in LVH is not solely the result of an increased amount of normal tissue. In less common cases, hypertrophy may be related to abnormal myocardial deposition of glycolipids, iron or amyloid, which also may affect ECG. Specifically, glycolipid overload as seen in Fabry disease is associated both with LVH and ECG changes mostly in the P‐wave duration,46 whereas some types of iron overload patients are more likely to develop hypertension and LVH,47 and subsequent LVH‐related ECG repolarization changes,48 and amyloid leads to reduced QRS amplitudes in general.41 More commonly, the hypertrophied myocardium may exhibit increased strain either in the absence or presence of focal scarring, may have genetic etiologies, and may include hypertrophied cardiomyocytes which undergo changes that can affect the ECG, including abnormal arrangement of cardiomyocytes, an increase in fibrous tissue and cell atrophy.49, 50 Additionally, the cardiomyocytes can suffer from ischemia which is an additional factor affecting the ECG and the structure of myocardial tissue. There may also be inflammatory components and adipose tissue, either as a part of the hypertrophic process or related to comorbidities.51, 52, 53

Detection of Focal and Diffuse Fibrosis by CMR

Hypertrophy is accompanied by an increase in connective tissue that has been documented by histopathological studies both in animal experiments and clinical studies.54, 55 In terms of affecting the ECG, fibrosis affects the impulse propagation at least in two ways. First, the proportion of electrically active to inactive tissue decreases. Second, the activation front is fractioned and the impulse propagation slowed. Focal fibrotic tissue can be considered as electrically inactive and nonconductive tissue, although a possible electrical connection between cardiomyocytes and fibroblasts has been described.56, 57

CMR can be used to detect and quantify both the extent and severity of both diffuse fibrosis and focal fibrosis. It is important to emphasize the difference between focal and diffuse fibrosis. CMR can be used to quantitatively characterize both focal and diffuse fibrosis by measuring the percent of myocardium comprised of extracellular space. The method is called extracellular volume fraction (ECV) CMR, and normal myocardium has an ECV of 20%–30%.33, 58 Focal fibrosis, also referred to as scar, typically forms following myocardial infarction or scarring of other nonischemic etiologies such as myocarditis, but also LVH of various origins, among others. Focal fibrosis is characterized by a high severity loss of cardiomyocytes where by ECV can measure up toward 50%–90% of the tissue by volume, and is comprised of replacement tissue including fibroblasts and collagen which develop in the chronic healing phase following an episode of necrosis of ischemic or nonischemic origin.33, 59

Detection of focal fibrosis in individuals with LVH is important considering the cardiac complications associated with focal fibrosis. Such complications include ventricular dysfunction, reduced coronary flow reserve, ventricular arrhythmias, and adverse prognosis.60, 61, 62 Moreover, these factors are also likely to affect the potential for regression of LVH following antihypertensive therapy or valvular surgery. Notably, little interest has been devoted to the analysis of QRS complex patterns in relation to the location and extent of fibrosis, or other electrically inactive tissue, in relation to the presence or potential for regression of LVH.

By comparison, diffuse fibrosis is a global low severity reactive phenomenon typically caused by hypertension, increased strain due to valvular disease, strain remote from focal scarring, age, diabetes, or other causes. In diffuse fibrosis, ECV can typically measure 30%–40%, and is composed of an increased amount of collagen in the interstitium of cardiomyocytes of normal quantity.33, 59 While ECV‐CMR is a relatively new technique for quantifying both the extent and severity of focal and diffuse fibrosis, CMR has traditionally been used to quantify the extent of focal fibrosis with the late gadolinium enhancement (LGE) technique. Focal fibrosis detected by LGE‐CMR is a frequent feature of LVH, regardless of its cause.39, 40 By comparison, diffuse fibrosis can only be detected by techniques such as ECV‐CMR and related techniques including postcontrast T1 mapping.63 An increase in myocardial ECV consistent with diffuse fibrosis has been found in such pathologies as aortic stenosis,64 dilated cardiomyopathy,65 adolescent obesity,66 LVH due to sarcomere mutations,67 and with increasingage.33 Furthermore, ECV‐CMR and related techniques have a potential to identify unexpected diffuse fibrosis in a significant proportion of athletes and veteran athletes.68 Finally, the combination of LGE‐ and ECV‐CMR provides a unique noninvasive evaluation of patterns of both focal and diffuse fibrosis in LVH. Detection of both focal and diffuse myocardial fibrosis is of utmost diagnostic importance since it is a marker of severity of LVH and a potential arrhythmogenic mechanism,69, 70, 71, 72 as well as a prognostic marker of mortality.73

The Use of CMR for Myocardial Tissue Characterization Beyond Fibrosis

LGE‐ and ECV‐CMR are, however, not specific for fibrosis. These techniques may identify any pathology which increases the myocardial extracellular space. While fibrosis increases ECV, other pathologies may also increase ECV, including edema or inflammation,36, 38 necrosis,37 as well as myocardial amyloid deposition.40, 41, 42 Importantly, diffusely increased ECV has been shown to provide incremental prognostic value for survival beyond ejection fraction.74 However, these conditions can be differentiated from focal and diffuse fibrosis because focal and diffuse fibrosis exhibit little or no increase in myocardial T1 in the absence of contrast administration, also called native T1. Furthermore, diffusely reduced myocardial native T1 is a specific finding for myocardial iron or glycolipid (Fabry) overload disease, both of which may exhibit LVH. Also, both T1 mapping and other techniques for fat imaging by CMR39 can identify focal fatty infiltration. An additional myocardial tissue characteristic of interest in LVH is myocardial disarray. Myocardial disarray can be evaluated by cardiac diffusion tensor imaging by CMR (DT‐CMR), and proof‐of‐concept and measurement variability studies have been performed in both healthy volunteers75 and patients with hypertrophic cardiomyopathy.76 Importantly, CMR can identify these alternative etiologies for, or related to, LVH in order to better understand the relationship between ECG findings and LVH‐related myocardial pathologies. See Table 1 for a summary of the myocardial characteristics detectable by CMR which affect the ability of the ECG to quantitatively assess LVH.

Table 1.

Myocardial Characteristics Detectable by Cardiovascular Magnetic Resonance Imaging (CMR) that Affect the Ability of the Electrocardiogram to Quantitatively Assess Left Ventricular Hypertrophy

Pathophysiological Characteristic CMR Technique
Left/right ventricular volumes and mass Volumetric measurement in cine images
Regional myocardialwallthickness 3D distribution in cine images
Focal myocardial fibrosis (scar) Late gadolinium enhancement
Diffuse myocardial fibrosis in the absence of scar ECV mapping
Diffuse myocardial edema/inflammation T1 mapping, T2 mapping
Focal myocardial edema/inflammation T1 mapping, T2 mapping,
T2‐weighted imaging
Focal myocardial fatty replacement T1 mapping,
Fat/water‐weighted imaging
Diffuse myocardial amyloid deposition ECV mapping, T1 mapping
Diffuse myocardial glycolipid deposition (Fabry) T1 mapping
Diffuse myocardial iron overload (siderosis) T1 mapping, T2* measurement
Myocardial disarray Diffusion Tensor CMR
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CMR = cardiovascular magnetic resonance imaging; ECV = extracellular volume; 3D = three‐dimensional. See text for further details on the respective techniques.

REGRESSION OF LVH BY ECG AND CMR

A topic related to diagnosing LVH is the ability to detect regression of LVH. Regression of LVH defined as reduction in LV mass is a topic with conflicting findings regarding the improved outcomes during pharmacological treatment for hypertension. On the one hand, an improved prognosis has been reported,52, 53, 54 and on the other hand, negative results have been reported.55, 56 CMR has been used to show that the reduction in LV mass following surgical treatment for aortic stenosis is related to reduction in myocardial cell size, with no reduction in the amount of diffuse fibrosis (extracellular collagen) detected by ECV‐CMR.77 The combination of CMR and ECG thus shows potential as a tool for elucidating how these changes are manifested in the ECG.

Taking together, CMR and ECG provide complementary information about the size and tissue characteristics of the myocardium, and could be used in combination to shape a new view of the agreements and discrepancies between the two methods in order to potentially move the assessment of LVH by ECG beyond the current estimation of LV mass.

FUTURE PERSPECTIVES

Even when taking into account the current state‐of‐the‐art CMR methods for myocardial tissue characterization in humans, there remain additional tissue characteristics of relevance for the ECG that currently cannot be elucidated by CMR. CMR cannot currently provide information on the electrical impulse generation of the action potential, electrical impulse propagation through the hypertrophied cardiomyocytes, the alterations in the architecture of intercellular connection components and micro‐heterogeneity. Of note, CMR has been used in animal models to noninvasively measure the absolute size of cardiomyocytes by assessment of the intracellular lifetime of water (τic). This CMR method is based on assessment the dynamics of a conventional clinical gadolinium‐based CMR contrast agent.78 While translation of this technique to humans remains to be undertaken, the technique shows promise considering that it has been validated histologically, and has been able to noninvasively detect and quantify increased myocardial cell size in a murine model of LVH.78

Although the main changes in the action potential of hypertrophied cardiomyocytes are observed during the repolarization phase, the ion channels involved in depolarization (the fast sodium current INa, L‐type calcium current ICa(L) and Na+–Ca2+ exchanger INa/Ca) are also affected, and further modified by a broad spectrum of changes observed in LVH. Such changes include variations in ion concentration (e.g., Na+, Ca2+), gene expression, metabolic changes, energy metabolism, and many others.89–86 While there exist theoretical possibilities to interrogate the role of sodium in the heart by 23Na‐CMR in relation to ECG findings,92 such capabilities have neither been explored nor are currently readily clinically available.

The velocity of electrical impulse propagation in a single hypertrophied cardiomyocyte has been shown to be increased. On the one hand, this is in accordance with cable theory, since the increase in diameter of the cardiomyocyte (analogously to the cable) leads to a decrease in the resistance and increase in conductivity.88,89 On the other hand, however, the intercellular coupling in hypertrophy is remarkably altered leading to slowed conduction velocity. The alterations include connexin43 (Cx43) expression and intracellular coupling reduction, and gap junction channels redistribution.90–94 The observed slowing of conduction velocity results in decrease in QRS amplitude and changes in QRS pattern, as documented in experimental and simulation studies.95–97

The nonuniform changes on the microscopic scale, such as in size of hypertrophied cardiomyocytes,98,99 Cx43 reduction, gap junction location,100,102 action potential morphology and membrane currents characteristics103,104 create microscopic heterogeneity. Together, these factors result in alteration of the normal ordered pattern of the microconduction pathway in LVH even when the activation front is not deformed. Whether or not these microscopic factors can be interrogated noninvasively in humans using CMR or other methods to better understand the ECG in LVH certainly constitute challenges to the field.

CONCLUSION

CMR provides a number of robust noninvasive techniques offering a spectrum of specific approaches for noninvasive in vivo characterization of pathological processes in the myocardium that could expand our understanding of ECG changes in LVH. The analysis of both agreement and discrepancies between ECG and CMR may provide information that can contribute to understanding the wide spectrum of ECG changes seen in LVH, and their diagnostic and prognostic importance. Using CMR and ECG as complementary methods will also open new questions based on understanding the diagnostic power of both methods—a space where we have to direct the future research to approach the LVH diagnostic problem systematically. While CMR has developed to be able to identify a number pathological processes in the myocardium, the characterization of LVH, in particular on the microscopic scale, is still lacking. While the agreement between CMR and ECG for characterizing LVH will likely remain far from perfect owing to the fundamental biophysical differences between the underlying technical principles of the techniques, improvements in the understanding of LVH have been made using CMR and ECG, and the new and emerging CMR and ECG techniques hold promise for continued improvements.

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