Three-dimensional echocardiography

An impressive body of information on hypertensive cardiac organ damage has accumulated in the last decades, thanks to a variety of noninvasive, rapidly evolving imaging techniques starting from standard echocardiography, currently regarded as an established, cost-effective, available cardiac imaging technique to detect and quantify the extent of morphologic and functional alterations of the heart secondary to hypertension [1]. The pivotal role of monodimensional and two-dimensional (2D) echocardiography has been further powered by new ultra-sonographic tools, primarily 2D/three-dimensional (3D) speckle tracking imaging and real time 3D echocardiography that provide a comprehensive assessment of myocardial mechanics and very accurate estimation of left ventricular mass (LVM) and of LVM/end-diastolic volume (EDV) ratio, an index of concentric geometry primarily utilized by cardiac magnetic resonance imaging (MRI) [2–4]. Although cardiac MRI is a highly reproducible method increasingly applied in clinical and research setting because of the undisputed potential to generate high-quality images of the heart at much higher resolution than echocardiography, it is not currently recommended for the assessment of hypertensive heart disease in clinical practice [5]. Similar to MRI, 3D echocardiography has the advantage to not to rely on geometric formulas for calculating LVM but measuring it directly. This allows greater accuracy and reproducibility in the evaluation of the LV structure and geometry in comparison with standard echocardiography. A number of studies conducted in healthy individuals from different ethnic groups have validated the accuracy of 3D echocardiography for LVM measurements against MRI finding an excellent correlation between the two methods [6]. This issue of the Journal reports the results of a cross-sectional investigation assessing the ability of 3D echocardiography in detecting subtle alterations of LV morphology (i.e. concentric geometry) according to LVM/EDV ratio, possibly reflecting early myocardial functional impairment in never-treated essential hypertensive patients [7]. Before commenting these findings in detail, some general considerations on available evidence in this research field may be useful. The diagnosis of hypertension in the early stages of its natural history as well as the established aptitude for its early nonpharmacological and pharmacological treatment has undoubtedly reduced the severity of cardiac target organ damage. Indeed, the prevalence of traditional electrocardiographic (ECG) and echocardiographic markers reflecting an advanced phase of hypertensive heart disease such as ECG strain, marked LV wall thickening and impaired LV function, has fortunately become much rarer than in the past [8]. Nowadays, increased LVM is regarded as the key echocardiographic marker of subclinical cardiac organ damage because of its value in predicting adverse outcome in hypertensive patients over and beyond conventional risk factors. Numerous additional echocardiographic parameters, including LV geometry, have been shown to predict cardiovascular events but their usefulness to reclassify risk level is not fully established. Indeed, the value of echocardiographically determined LVM in predicting cardiovascular outcomes has been well established by observational and intervention studies carried-out in different clinical settings such as general population samples, hypertensive cohorts, diabetic patients, patients with coronary artery disease, heart failure, and chronic kidney disease. These studies have consistently shown a direct association between LVM over a wide range of values and incidence of cardiovascular events and all-cause mortality, revealing a continuous relationship between LVM and outcomes [9]. This is because an increase in LVM is the result of the combined effect on cardiac structure of haemodynamic and nonhaemodynamic unhealthy factors. In particular, a growing body of evidence supports the interplay between blood pressure (BP) and/or volume overload with genetic, ethnic, humoral, hormonal factors, and comorbidities (i.e. diabetes, metabolic syndrome, and dyslipidemia) as major determinants of LVM. As for LV geometry, the clinical and prognostic meaning is less clearly tried. The conventional echocardiographic classification of LV geometry proposed by in the early 90s based on LVM and relative wall thickness (RWT) constitutes four LV patterns, namely normal LV geometry, concentric remodelling, eccentric, and concentric hypertrophy [10]. These patterns have been shown to be associated with different degrees of LV systolic/diastolic function, left atrial size and function, plasma volume, peripheral resistances, BP overload, and extra-cardiac organ damage [11,12]. It has been recently suggested that changes in LV morphology and function may in part also depend on the type of body mass composition. Investigators of Study of Health in Pomerania reported that an increase in fat mass was associated with LV concentric remodeling and impairment of systolic and diastolic function parameters, whereas an increase in free-fat mass was associated with LV eccentric remodeling and improved systolic and diastolic functional variables [13]. Whether abnormal LV geometric patterns, however, carry prognostic information beyond that provided by LVM itself remains a matter of debate [14]. A possible explanation for the inconsistent findings provided by various studies on this issue concerns the methodological limits of the traditional classification of LV geometric patterns based on a simple linear index of LV concentricity (radius to thickness ratio) and not taking into account absolute values of LV wall thickness and internal dimensions. An up-dated classification of the abnormal LV geometric patterns based on the ratio between LVM to EDV as assessed by MRI, has been introduced by investigators of the Dallas Heart Study [15]. This method allows to identify four LVH sub-types, namely eccentric nondilated (indeterminate) and eccentric dilated LVH, concentric nondilated and concentric dilated LVH. The potential utility of these sub-classifications was demonstrated by finding significant differences in biomarkers reflecting pathological cardiac stress between the new subgroups. Individuals with concentric-dilated LVH had a lower LV ejection fraction and higher N-terminal prohormone of brain natriuretic peptide (NT-pro-BNP) and BNP levels than those with isolated thick hypertrophy. Furthermore, individuals with dilated hypertrophy vs. those within indeterminate hypertrophy had higher indexed LVM, lower LV ejection fraction, and higher levels of natriuretic peptides. While in turn, the individuals with indeterminate LVH had similar levels of LV function and biomarkers of cardiac stress as their counterparts without LVH. It is worth underlining that the independent prognostic significance of LV ventricular geometry even based on this new classification remains uncertain [16]. In the Pressioni Monitorate e Loro Associazioni (PAMELA) study, only concentric nondilated LVH maintained a significant prognostic value for incident cardiovascular mortality after adjustment for baseline values of LVM index, this was not the case for nondilated and eccentric dilated LVH [17]. In initially untreated patients with hypertension enrolled in the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study, after adjustment for several independent covariables, concentric-dilated LVH entailed a significant greater risk of cardiovascular events. However, this LV geometric pattern lost statistical significance when LV mass was entered into the model [18]. The study by Lembo et al.[7] offers a novel piece of information on the prevalence of concentric geometry and its relation with LV function in a selected group of untreated essential hypertensive patients by applying 3D echocardiography, a technique, which provides a better definition of cardiac anatomy and a more reproducible measurement of cardiac structures than 2D or M-mode echocardiography. The authors performed standard 2D, echo-Doppler, and 3D echocardiography in 128 consecutive newly diagnosed patients (83 men and 45 women). They aimed at identifying a 3D LVM/EDV ratio-based phenotype of concentric geometry and compare it with that based on 2D RWT. To this purpose, the study population was divided into two groups according to the upper 95% confidence interval (LVM/EDV ratio cut-offs: 1.22 in men and 1.23 in women) obtained in a reference healthy population of 90 normotensive individuals. As a consequence of that choice, ratios of 1.23 or more were considered as characteristic for concentric geometry (n = 48). The prevalence of LV concentric geometry based on 3D LVM/EDV ratio in the whole hypertensive population was 37%, whereas using 2D RWT concentric geometry (2× posterior wall thickness/end diastolic diameter ≥0.42) the concentric pattern was diagnosed in 31 patients (24%, P = 0.03), the majority of them (24 out of 31) included in the group with elevated 3D LVM/EDV ratio. Compared with patients with normal 3D LVM/EDV ratio, those with concentric geometry showed a greater female prevalence (46 vs. 29%, P = 0.08) and mean age (51 ± 13 vs. 39 ± 14 years, P < 0.001). Despite these demographic differences, the two groups had similar levels of BMI, SBP and DBP, and heart rate. Comparing the 2D Echo-Doppler data of patients with and without concentric geometry, the former group showed a higher RWT, E/e’ ratio, and a reduced E/A ratio, without, however, differences in LVM indexed to h2.7 and LV ejection fraction. On the contrary, 3D echocardiography was able to show a modest but significant increase in LVM index in patients with concentric geometry (+3.2 g/m2.7), whose stroke volume and cardiac output were much lower than those of patients with LV normal geometry (approximately −20 ml and −1.3 l/min, P < 0.001 for both). In the entire hypertensive population, the factors independently related to the stroke volume were, in ranking order, 3D LVM/EDV ratio, age, and female sex. Thus, a reduced stroke volume seems to be a marker of a concentric geometry in hypertension. Some limitations and strengths of this interesting study deserve to be further commented. The role of the factors responsible for concentric remodeling remains elusive as BMI and BP, two key variables in the determination of LV geometry, do not show difference between the two groups. This result can be substantially because of the small number of patients included in the present study. It is worthy of note, as clearly specified by the authors, that the study does not intend to provide normative values for the diagnosis of concentric geometry based on 3D echocardography, as they have been obtained in 90 normotensive individuals with an average age of 40 years and a BMI of 24.5 kg/m2 not representative of the general population seen in daily clinical practice. The choice of newly diagnosed, drug-naïve patients is one of the strengths of the study as it has made it possible to avoid the confounder impact of antihypertensive drugs on LV geometry. Finally, the independent association of LV concentric geometry, as defined by 3D LVM/EDV, with reduced stroke volume indicates that this harmful duo can be frequently identified even in the setting of untreated essential hypertensive patients without comorbidities. In conclusion, the study by Lembo et al.[7] suggests that 3D echocardiography may expand our ability to identify early changes in LV geometry and systolic performance in hypertensive patients apparently free of subclinical cardiac organ damage assessed by standard echocardiography and opens new perspectives in the evaluation of hypertensive heart disease. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.