LV mass indexed to BSA, g/m2 < 96 in women,< 116 in men (when BMI 30 kg/m2)
LV mass indexed to height 2.7, g/m 2.7 < 45 in women,<49 in men (when BMI > 30 kg/m2)
LV relative wall thickness (RWT) < 0.43
Transmitral flow
Peak E velocity, cm/s
Peak A velocity, cm/s
E/A ratio, under quiet breathing and if necessary during Valsalva maneuver
E wave deceleration time, ms
LV isovolumic relaxation time, ms
Tissue Doppler imaging
e′ septal, cm/s ≥ 8
e′ lateral, cm/s ≥ 10
E/e′ ratio (septal and lateral averaged) < 13
LV ejection fraction, % > 55
Left atrial diameter, cm < 3.9 in women,<4.1 in men
Left atrial volume indexed to BSA, ml/m2 < 34 (ESH ESC) (mild, EAE, ASE < 29)
Aortic diameter at the sinuses of Valsalva, indexed to BSA, cm/m2 < 2.1
2.1.1 Cardiac Structure
In hypertensive patients, the main goal of echocardiography is the detection of LVH, and to this regard, the calculation of left ventricular mass (LVM) is mandatory. Hypertrophy cannot be defined according to wall thickness only, and wall thickness alone is not predictive of cardiovascular risk [3, 4].
Both mono-dimensional (M-mode) and two-dimensional (2D) echocardiography have been used in the measurement of LVM and have been anatomically validated [5, 6].
Linear measurements of interventricular septum wall thickness (IVST), as well as of left ventricular internal diameter (LVID) and posterior wall thickness (PWT), should be obtained with the beam perpendicular to the minor axis at the mitral valve leaflet tips, in the left parasternal acoustic window, at end diastole, from 2D-targeted M-mode, or directly from 2D images. Calculation of LVM is based on a mathematical formula assuming a prolate ellipsoid shape for the LV (LVM = 0.8 × (1.04 [(LVIDD + PWTD + IVSTD)3 – (LVIDD)3]) + 0.6 g, where LVIDD is left ventricle internal dimension in diastole, PWTD is posterior wall thickness in diastole, and IVSTD is intraventricular septal thickness in diastole [2].
LVM normalization for an anthropometric measure, such as height or body surface area, is needed to identify LVH. Weight and height should be measured simultaneously to the echocardiographic examination, avoiding the use of patients self-reported data, that is a source of potential error in the indexation of LVM and finally in the risk stratification [7]. The indexation of LVM to body surface area underestimates the prevalence of LVH and the LVH attributable risk in populations with overweight or obese subjects [8]. In these patients indexation of LVM for height (height to the allometric power of 1.7 or 2.7) can be considered. Indexation by height 2.7 was derived from a cohort of Caucasian children and adults, and indexation by height 1.7 was derived from a study including 1,035 Chinese and Caucasian adults [9, 10]. Recent data from the Echocardiographic Normal Ranges Meta-Analysis of the Left heart (EchoNoRMAL) project suggest that different allometric power for BSA and height should be applied according to gender and ethnic group [11].
The evaluation of geometric adaptation of the left ventricle to the increased hemodynamic load implies the calculation of the relative wall thickness (RWT or wall to radius ratio, i.e., the ratio between LV end-diastolic wall thicknesses and diameter) and may significantly differ among hypertensive patients [12]. A cutoff value of 0.42 permits categorization of an increase in left ventricular mass as either concentric (RWT = or > 0.42) or eccentric (RWT < 0.42) hypertrophy and also allows the identification of concentric remodeling, defined as a normal left ventricular mass with increased RWT > 0.42 [1].
These different LV geometric patterns are associated with different hemodynamic characteristics, and peripheral resistances are greater in patients with concentric geometry, while cardiac index is increased in those with eccentric hypertrophy [13]. In addition concentric remodeling, eccentric and concentric hypertrophy all predict an increased incidence of cardiovascular disease, but concentric hypertrophy has consistently been shown to be the condition that most markedly increases the risk, even in very high-risk patients [14–16]. Very recently, a new reclassification of LVH, based on LVM, relative wall thickness, and LV dilatation, has been proposed in hypertensive patients [17]. The subclassification of hypertensive patients with eccentric LVH into groups with normal or increased LV chamber volume revealed that the latter, but not the former, predicted increased risk for all-cause and cardiovascular mortality and cardiovascular events. In contrast, the subclassification of patients with concentric LVH into groups with normal or increased LV chamber volume revealed the association of both dilated and non-dilated concentric LVH with poor outcome. The low-risk group of patients with relatively mild LVH, no concentric geometry, or dilatation among patients with eccentric LVH had a similar risk of all-cause mortality or cardiovascular events as patients with normal LVM. The verification of the enhanced prognostic power of the 4-group classification of LVH in other populations is needed before recommending that this more refined approach replaces the established classification of LVH into eccentric and concentric subgroups.
Evaluating LVM increase by taking into account gender and cardiac loading conditions has been proposed in order to discriminate the amount of LVM adequate to compensate the hemodynamic load (adequate or appropriate) from the amount in excess to loading conditions (and therefore inappropriate or not compensatory) [18]. LVM is inappropriate when the value of LVM measured in a single subject exceeds the amount needed to adapt to the stroke work for that given gender and body size.
Technical variability represents a potential limitation of echocardiographic measurement of LVM. An assessment of LVM reproducibility has shown that LVM changes of 10–15 % may have biological significance in individual patients [19]. When changes in LVM inappropriateness are evaluated, changes of 15–25 % may reflect true changes [20]. Real-time 3D echocardiography permits a more reliable measurement of LVM, and its accuracy has been shown to compare favorably with that of cardiac magnetic resonance imaging [21]. Despite the relationship between LVM and incidence of cardiovascular events is continuous [22], several criteria for the diagnosis of echocardiographic LVH have been proposed. These criteria are based on the distribution of LVM index in general population samples (average LVM value plus one standard deviation in apparently healthy population-based samples) or on the association between increased values of LVM and occurrence of cardiovascular events in longitudinal studies. The presence of echocardiographic LVH is associated with an incidence of cardiovascular events equal or greater than 20 % in 10 years [23].
The American Society of Echocardiography and the European Association of Echocardiography (EAE/ASE) have published ranges for several echocardiographic parameters derived from a population of about 500 multiethnic, normotensive, and normal weight subjects, and the Pamela study has provided new reference limits in an Italian population [2, 24]. A revision of previous diagnostic criteria will probably come from new ethnic and gender-specific group reference values from the Echocardiographic Normal Ranges Meta-Analysis of the Left heart (EchoNoRMAL) project [11].
2.1.2 LV Diastolic Function
In hypertensive patients diastolic dysfunction is characterized by alterations of LV relaxation and filling that may precede abnormalities of systolic function [25]; these abnormalities should be interpreted according to the presence of LVH or concentric geometry in order to give a correct interpretation of LV diastolic function and filling pressure parameters. In fact, in patients with LV hypertrophy or concentric remodeling, LV relaxation is usually slowed, with a decrease in early diastolic filling; in the presence of normal left atrial pressure, a greater proportion of LV filling is shifted from early to late diastole after atrial contraction. Therefore, the presence of a predominant early filling in these patients should suggest the presence of increased LV filling pressures [2, 26].
An improvement in the study of LV diastolic function has been provided by the assessment of Doppler transmitral flow velocities and by pulsed Doppler tissue imaging (DTI). LA size is a further parameter to be assessed in the evaluation of diastolic function [27].
The influence of factors such as age, gender, body mass index, heart rate, and blood pressure on Doppler flow velocities has been extensively evaluated. Normal values for Doppler parameters according to age groups have been assessed in a relatively small sample of 117 subjects [28].
The analysis of myocardial velocities at the mitral annulus may reveal an increase in left ventricular filling pressure; in respect to Doppler transmitral flow velocities, DTI velocities show no “pseudonormalization” pattern [29, 30]. The average value of DTI velocities at the septal and lateral sides of the mitral annulus should be used for the assessment of global LV diastolic function. The E/e′ ratio represents a reliable estimate of LV filling pressures, and different cutoff values have been proposed for the definition of normal or progressively higher LV filling pressure. E/e′ ratio > 13 indicates a severe increase in LV filling pressure. In the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) echocardiographic sub-study, E/e′ ratio was the strongest predictor of first cardiac events, independent of LVM and geometry [31]. The combination of transmitral flow velocities, mitral annulus DTI velocities, and left atrial volume should be used for diastolic dysfunction diagnosis and stratification [26]. The grading suggested by the EAE/ASE recommendations is an important predictor of all-cause mortality, as shown in the Olmsted County epidemiological study.
An accurate measurement of left atrial (LA) size should be an integral part of the standard echocardiogram in hypertensive patients. LA enlargement may reflect the increase in left ventricular filling pressure; in patients with preserved systolic function, it may be a marker of diastolic dysfunction and is predictive of an increased risk of atrial fibrillation, stroke, heart failure, and mortality. This has been shown by the measurement of LA anteroposterior linear dimension by M-mode from the parasternal long axis view and by the more accurate evaluation of LA volume from 2D images. The measurement of LA volume is recommended both in clinical practice and in research studies, and most guidelines recommend the biplane area-length method. The recent 2013 ESH/ESC guidelines for the management of arterial hypertension and the EAE/ASE guidelines recommend a cutoff value of >34 ml/m2 for left atrial enlargement [1].
Compared to the conventional two-dimensional approach, 3D echocardiography appears superior in the assessment of LA volume; at present, however, this application is limited to research studies. The same consideration applies to several other parameters of left atrial function, based on 2D or 3D measures, conventional and tissue Doppler, or strain rate imaging [32, 33].
2.1.3 LV Systolic Function
LV dysfunction includes segmental and global alterations of LV that may differently affect pump function and prognosis. In uncomplicated hypertensive patients, LV shortening fraction (FS) and ejection fraction (EF) express endocardial fiber shortening and are usually preserved or even “supernormal,” mainly in the presence of concentric geometry [2]. However, midwall myocardial fibers contribute to a greater extent than subendocardial fibers to LV ejection, and the difference between the conventional and midwall indexes of LV systolic function is more evident in the presence of a concentric LV geometry; therefore, in the presence of a concentric LV geometry, LV midwall fractional shortening is considered a more appropriate index of LV systolic function than conventional FS [34–36].
LVEF, derived from two-dimensional calculation of the LV end-diastolic volume (EDV) and the LV end-systolic volume (ESV) according to the modified Simpson method (average of apical four and two chamber views), is the most sensitive index of systolic ventricular function with a high prognostic value. LVEF values >55 % define a normal systolic function, while a slight or moderate reduction in systolic function is present when EF values are between 45 % and 55 % and between 35 % and 45 %, respectively; values below 35 % identify patients with severe LV systolic dysfunction.
In the absence of major structural abnormalities, a single-plane measurement of the LV area is obtained from the apical four-chamber window. The longitudinal myocardial systolic velocity (Sm), measured by TDI at the mitral annulus level, has been proposed as a reliable and accurate index of myocardial fiber performance, independent of LV preload and afterload. In normal conditions, its value is higher than 8 cm/s and in severe pathological conditions is less than 5 cm/s [26].
More recently a 3D probe (multiplane) has become available and allows the calculation of LV volumes by the Simpson triplane method [32, 37]. The accuracy of 3D echocardiographic in the measurement of LV volumes has been confirmed by the comparison with magnetic resonance imaging [38]. Speckle-tracking echocardiography, a technique based on the analysis of interference patterns and natural acoustic reflections generated by tissue motion which are ultimately resolved into angle-independent 2D and 3D strain-based sequences, may reveal early subclinical abnormalities in regional systolic and diastolic LV myocardial function in hypertension and can also be used to evaluate left atrial mechanics [39, 40].
2.1.4 Aortic Root
Finally, the measurement of the aortic size provides useful information in hypertensive patients undergoing echocardiography. As hypertension exerts a relevant effect on aortic size, an enlarged aorta has been associated with adverse cardiovascular outcomes and mortality.
Most guidelines currently underline the importance of including measurements at the aortic valve annulus (i.e., the hinge point of aortic leaflets) and at the sino-tubular junction in addition to the standard approach of measurement of aorta diameter at the sinuses of Valsalva from the 2D view in order to obtain the largest diameter. Furthermore, the subcostal approach allows in a large majority of patients the evaluation of the abdominal aorta, and these measurements are therefore recommended in clinical practice. Indexation for BSA is recommended for clinical purposes, a prognostically validated upper normal threshold for the diameter at the Valsalva sinus is 2.1 cm/m2, and nomograms taking into account the age of patients are also available. In obese or overweight patients, indexation to body height should be considered [41].
2.2 Prevalence
Prevalence of left ventricular hypertrophy (LVH) in patients with hypertension mostly derives from population-based studies and selected hypertensive cohorts, with a quite large range according to demographic characteristics of subjects and to cutoff criteria used for the diagnosis. This variability is also potentiated by the different criteria used in different studies to calculate LVH. Cuspidi et al. have analyzed the available studies in 2012 and found that LVH prevalence consistently varied among studies from 9 % to 77 %, being lowest in population-based studies (<10 %) and highest in high-risk hypertensive patients (58–77 %) [42].
In a multicenter Italian study conducted in several hypertension specialist outpatient clinic, the prevalence of LVH was 60 % according to sex-specific criteria of LVM indexed by height to the 2.7 power and 37 % according to sex-specific criteria for LVM indexed by BSA [7].
2.3 Change with Treatment
Antihypertensive treatment is associated with a significant reduction in LVM. The magnitude of the decrease is related to the baseline LVM; according to variability in LVM measurements, only changes >10–15 % can be considered of biological relevance. The correlation between changes of LVM and changes in clinic BP is modest and increases when 24 h BP is considered [43].
Among all classes of antihypertensive drugs, ACE inhibitors, angiotensin receptor blockers, and calcium antagonists seem to be more effective as compared with beta-blockers [44]. It should kept in mind, however, that in most studies patients were receiving a combination of drugs (usually with a diuretic) and not monotherapy. Therefore, the efficacy of antihypertensive treatment in inducing adequate and long-term blood pressure control seems more important than the choice of a specific class.
A normalization of LVM is more difficult and cannot be always reached in women [25], obese or diabetic patients [45], elderly subjects with isolated systolic hypertension [46], or patients with coronary artery disease, despite adequate treatment. A normalization of LV geometry is also possible, and in the LIFE study, a conversion of concentric to eccentric LVH was reported in 34 % of subjects, whereas only 3 % of patients with eccentric LVH transitioned to concentric LVH [47]. In the ASCOT study, a modest change in LVM and persistence of elevated relative wall thickness were observed from the first to the third year of therapy [48].