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11 January 2026

25 Pages

Echocardiographic Assessment of Left Ventricular Diastolic Function in Adults Between Old and New: Progress and Challenges

and
1
Cardio-Thoracic and Vascular Department, Cardiology Division, Gorizia & Monfalcone Hospital, ASUGI, 34170 Gorizia, Italy
2
Cardiology, Policlinico San Giorgio, 33170 Pordenone, Italy
*
Author to whom correspondence should be addressed.
Diagnostics2026, 16(2), 235;https://doi.org/10.3390/diagnostics16020235
This article belongs to the Special Issue Recent Advances in Echocardiography, 2nd Edition
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Abstract

Echocardiographic left ventricular (LV) diastolic function assessment represents one of the mainstays for routine, comprehensive transthoracic echocardiography in adults. Estimation of LV filling pressures is an integral part of LV diastolic function evaluation. Additionally, LV diastolic function assessment is crucial for the study of subjects with potential heart failure with preserved LV ejection fraction. Beyond the “old” LV diastolic function parameters, to date, mostly strain-based (and generally artificial intelligence-assisted) additional “new” echocardiographic techniques have emerged to optimize the study of LV diastole. The purpose of the present narrative critical review is to report and discuss the optimal echocardiographic assessment of LV diastolic function in light of the recent literature, with the aim of trying to outline the gaps in the current evidence in view of future developments. To date, multiparametric diastolic evaluation and grading seem advisable, using as many “old and new” measurements as possible—associated with their adequate selection related to the patients’ comorbidities—aiming to cumulatively increase the advantages of diastolic parameters and possibly minimize their limitations. Taking into account the considerable number of echocardiographic measurements to perform and describe, at present, the timing of optimal echocardiography performance and reporting should be adequately adapted to the current technical needs and real-life routine clinical practice. Importantly, contextual clinical and (if needed) multimodality assessment should be included in the diagnostic workflow, in order to enable a more individualized approach.

1. Introduction

Echocardiographic left ventricular (LV) diastolic function evaluation represents one of the mainstays for routine, comprehensive transthoracic echocardiographic examination in adults [1,2,3,4,5]. Estimation of LV filling pressures (FPs) is an integral part of LV diastolic function assessment [1,2,3]. Moreover, adequate LV diastolic function evaluation is crucial for the study of patients with potential heart failure (HF) with preserved LV ejection fraction (HFpEF) [1]. Beyond the “standard” LV diastolic function parameters, to date, mostly strain-based echocardiographic techniques and a number of combined parameters have emerged to refine the study of LV diastole [1,6]. Furthermore, the role of artificial intelligence (AI)-assisted echocardiographic modalities is becoming increasingly important in this field, despite a number of limitations [1,7,8,9,10,11,12,13]. The purpose of the present narrative critical review is to report and discuss the optimal echocardiographic assessment of LV diastolic function in light of the recent literature, with the aim of trying to outline the gaps in the current evidence in view of future developments.

2. LV Diastolic (Dys)Function: Basic Pathophysiological Considerations and Clinical Implications

Historically, the definition of diastole is considered tricky and controversial [14]. During the cardiac cycle, the diastole generally includes both a ventricular isovolumic relaxation phase, a passive filling period, and an atrial contraction phase (Figure 1); notwithstanding, diastole might be considered the phase that divides two such consecutive contraction–relaxation transients, namely, including the diastasis and atrial contraction phases [14]. Effectively, some authors [14] have emphasized that a decrease in force and relengthening during myocardial relaxation of an afterloaded contraction may be parts of one activity transient, as well as both a decrease in ventricular pressure and increase in ventricular volume during early rapid filling may be in close relation to such activity transient (thus, considered as part of systole) [14]. Physiologically, heart rate inversely influences the duration of diastole [14]. Diastolic dysfunction causes increased resistance to ventricular filling, an inappropriate upward shift of the diastolic pressure–volume relationship, potential subendocardial ischemia, ventricular remodeling/hypertrophy, and finally leads to symptoms and signs of congestion and HF [1,2,3,14]. Therefore, that pathophysiological process causes both hemodynamic and structural modifications on the complex three-dimensional (3D) organization of the myocardial fibers, evaluable by a number of helpful “old and new” parameters—including Doppler and strain measurements—for adequate characterization, clinical, and prognostic purposes [1,5,14,15,16,17].
Figure 1. Illustrated explanation of the relationship between cardiac cycle and LV pressure–volume loop, focusing on diastole, as well as main parameters for assessing LV diastolic function. AVC, aortic valve closure; AVO, aortic valve opening; AV and Dur, A-wave (peak) velocity and duration; ARV and Dur, AR-wave (peak) velocity and duration; D, D-wave (peak) velocity; EV and DT, E-wave (peak) velocity and deceleration time; ED, end-diastole/diastolic; GLS, global longitudinal strain; IVRT, isovolumic relaxation time; LA, left atrium/atrial; LAVi, LA volume index; LV, left ventricle/ventricular; LVP, left ventricular pressure; LVV, left ventricular volume; MVC, mitral valve closure; MVO, mitral valve opening; PRED, peak pulmonary regurgitation ED velocity; S, S-wave (peak) velocity; TE-e’, TI calculated by subtracting TE (TI between the peak R-wave on ECG and the onset of E-wave) from Te’ (TI between the peak R-wave on ECG and the onset of e’-wave), namely, Te’—TE; TI, time interval; Vp/EV/Vp, early diastolic flow propagation velocity (Vp) and EV/Vp ratio; ^, and derived S/D ratio; °, and derived IVRT/TE-e’ ratio; *, and derived E/A ratio; †, and derived E/e’ ratio; ‡, and AR-A duration (see text, tables, and references).

3. Echocardiographic Evaluation of LV Diastolic Function by Primary Techniques

Primary echocardiographic techniques for evaluating LV diastolic function mainly include Doppler ultrasound parameters, left atrial (LA) volume index (LAVi), and LV global longitudinal strain (GLS) [1,2,3].

3.1. Doppler Ultrasound Techniques

Primary Doppler ultrasound measurements first evaluate transmitral inflow parameters, including E-wave velocity and deceleration time (DT), A-wave velocity and duration, and finally the E/A ratio [1] (Table 1; Figure 1, Figure 2, Figure 3 and Figure 4A). Generally, these parameters are integrated with tissue Doppler imaging (TDI) measurements (e’ velocity and a’ velocity), even in association (such as the E/e’ ratio and average E/e’ ratio), in order to suggest increased LV FPs as well [1] (Table 1; Figure 1, Figure 2 and Figure 4B).
Table 1. Main primary echocardiographic parameters for assessing LV diastolic function: transmitral inflow and TDI at mitral annulus [1,2,3,17].
Figure 2. LV diastolic dysfunction diagnostic algorithm. LA, left atrium/atrial; LAP, LA pressure; LARS, LA reservoir strain; LAVi, LA volume index; LV, left ventricle/ventricular; *: mentioned age-specific ranges may be considered for assessing reduced e’ or E/A, after excluding LA dilation in particular conditions, including anemia, AF, AFL, MV disease, or athletes; **: after increased LV mass exclusion in athletes, another finding consistent with diastolic dysfunction is LV mass index >115 g/m2 in men or >95 g/m2 in women (see text, tables, and references).
Figure 3. Algorithm of LAP estimation and LV diastolic function grading (exceptions include moderate-to-severe mitral annular calcification, mitral stenosis, severe primary mitral regurgitation, history of mitral valve repair/replacement, history of mitral–transcatheter edge-to-edge repair, atrial fibrillation, history of heart transplantation, LV assist device, non-cardiac pulmonary hypertension, and pericardial constriction). A, A-wave (peak) velocity (measured in m/s); D, peak D-wave velocity (measured in cm/s); DD, diastolic dysfunction; E, peak E-wave velocity (measured in m/s); E/A, E/A (velocity) ratio (adimensional); e’, peak e’-wave velocity (measured in cm/s); E/e’, E/e’ (velocity) ratio (adimensional); IVRT, isovolumic relaxation time (measured in ms); LA, left atrium/atrial; LAP, LA pressure; LARS, LA reservoir strain (peak atrial longitudinal strain); LAVi, LA volume index (measured in mL/m2); LV, left ventricle/ventricular; PASP, pulmonary artery systolic pressure (measured in mmHg); S, peak S-wave velocity (measured in cm/s); S/D, S/D (velocity) ratio (adimensional); sympt, if symptom/s; TR, peak tricuspid regurgitation velocity (measured in m/s); *, if none available/reliable, supplemental/secondary methods may be considered, including changes to mitral inflow profile with Valsalva maneuver, L-wave velocity, Ar-A duration, peak pulmonary regurgitation end-diastolic velocity, and pulmonary artery diastolic pressure ≥ 16 mmHg (see text, tables, and references).
Figure 4. Examples of transmitral inflow (A) and TDI (B) parameters assessment. A, peak A-wave velocity (after ECG P-wave, peak late diastolic modal velocity; measured in m/s); ADUR, A duration (measured in ms); a’, peak a’-wave velocity (after ECG P-wave, peak late diastolic modal velocity; measured in cm/s); DT, deceleration time (measured in ms); E, peak E-wave velocity (after ECG T-wave, peak early diastolic modal velocity; measured in m/s); E/A, E/A (velocity) ratio (adimensional); e’, peak e’-wave velocity (after ECG T-wave, peak early diastolic modal velocity; measured in cm/s); s’, peak s’-wave velocity (at ECG T-wave, peak systolic modal velocity; measured in cm/s); TDI, tissue Doppler imaging. Note: sweep speed at 100 mm/s (see text, tables, and references).
Doppler study on pulmonary venous (PV) inflow provides other useful parameters, such as S-wave velocity, D-wave velocity, S/D ratio, and AR velocity and duration [1] (Table 2; Figure 1 and Figure 5).
Table 2. Main primary echocardiographic parameters for assessing LV diastolic function: PV inflow, TR, IVRT, LAVi, and LV GLS [1,2,3,6].
Figure 5. An example of PV inflow parameters assessment. AR, peak AR-wave velocity (after ECG P-wave, peak late diastolic modal velocity; measured in cm/s); ARDUR, AR duration (measured in ms); D, peak D-wave velocity (after ECG T-wave, peak early diastolic modal velocity; measured in cm/s); PV, pulmonary veins/venous; S, peak S-wave velocity (at ECG T-wave, peak systolic modal velocity; measured in cm/s); S/D, S/D (velocity) ratio (adimensional). Note: sweep speed at 100 mm/s (see text, tables, and references).
Finally, both isovolumic relaxation time (IVRT) and continuous-wave (CW) Doppler investigation of tricuspid regurgitation (TR) velocity may be helpful in assessing diastolic function and LA pressure [1] (Table 2; Figure 1, Figure 3 and Figure 6A,B).
Figure 6. An example of IVRT evaluation (A) and CW Doppler study on TR velocity (B). These parameters may be helpful for contributing to assess diastolic function and LA pressure. CW, continuous-wave; IVRT, isovolumic relaxation time (measured in ms); TR, tricuspid regurgitation; TRV, peak TR velocity. Note: sweep speed at 100 mm/s (see text, tables, and references).

3.2. LA Volume

As mentioned, LAVi is also noted in the primary techniques for assessing LV diastolic function [1] (Table 2; Figure 1, Figure 2, Figure 3 and Figure 7A,B). LAVi is one of the most important criteria for detecting LV diastolic dysfunction and estimating FPs, as well as being a predictor of HF/death, although evidence of a clear prognosis-related threshold is not available to date [1] (Figure 1, Figure 2 and Figure 3). Particularly, a certain degree of physiological LA enlargement is possible, such as in athletes [1,2,3].
Figure 7. An example of LAVi evaluation, assessed from 2D apical four-chamber (A) and two-chamber (B) views. Note: 2D, two-dimensional; LAVi, left atrium/atrial volume index (measured in mL/m2) (see text, tables, and references).
Notably, paying attention to avoid any LA image foreshortening, precisely acquiring end-systolic frames [generally, either one or two frame/s before mitral valve (MV) opening], and exactly tracing the LA area are crucial [1] (Table 2; Figure 7A,B).
Despite not being included in the main parameters, the ratio between LA minimal volume (measured at the LV end-diastolic phase) and LV end-diastolic volume (the so-defined “left atrioventricular coupling index”) has been proposed for assessing LV diastolic function—being associated with diastolic dysfunction severity—as well as an independent predictor of outcomes in the presence of HF [18,19,20,21,22]. Notwithstanding, the left atrioventricular coupling index currently seems to perform worse as a prognostic index in the presence of HF with reduced EF in comparison with HFpEF [21]. Moreover, its prognostic role has mainly been demonstrated in selected subjects with stable HF, sinus rhythm, and in the absence of previous valvular interventions, thus further investigations are needed [21].

3.3. LV GLS

Importantly, in light of the recent recommendations, LV GLS represents a “new entry” among primary echocardiographic parameters for evaluating LV diastolic function [1] (Table 2; Figure 1 and Figure 8A–D). Despite LV GLS not being a “direct” index of LV diastolic function, LV GLS has an important “indirect” role [1]. Effectively, reduced LV GLS is present in some patients with diastolic dysfunction associated with normal EF, either with or without HFpEF [1]. Moreover, LV GLS represents an HFpEF evaluation parameter, and is related to worse outcomes in a number of cardiovascular diseases associated with altered diastolic function, including left-sided valvular heart disease and cardiomyopathies [1].
Figure 8. An example of LV GLS evaluation, assessed from 2D apical four-chamber view (A), two-chamber view (B), three-chamber view (C), and reported “bull’s eye” GLS plot (D), respectively. Note: 2D, two-dimensional; GLS, global longitudinal strain; LV, left ventricle/ventricular (see text, tables, and references).
Tran et al. [23] recently enrolled 579 patients in a cross-sectional study, demonstrating that diabetes, concentric LV remodeling/hypertrophy, and LV diastolic dysfunction significantly correlated with abnormal LV GLS (p-value < 0.05). Limitations mainly included the cross-sectional study design, only two expert operators involved in the echocardiographic assessment, and some important factors being inadequately addressed, such as length of hypertension and related-conditions management [23].
Although it has the potential property of detecting subtle LV dysfunction—even in the presence of preserved LV EF—, in association with important diagnostic and prognostic implications, a number of limitations should be considered in routine clinical practice [1,6]. LV GLS is possibly influenced by acoustic window (including the role of chest shape), frame rate, preload/afterload, patients’ age, different normality cut-off values, inter-vendor variability, and the literature-mentioned concern associated with the test–retest variability [1,6,24]. Furthermore, the wide overlap of GLS standard deviations between groups at the population level can make the application of a precise physiological meaning to each individual value in each single subject challenging [6].

4. Echocardiographic Evaluation of LV Diastolic Function by Secondary Techniques

Secondary parameters are mainly assessed using Doppler ultrasound techniques, and include the following: Valsalva maneuver-related transmitral inflow analysis (Table 3; Figure 1, Figure 3 and Figure 9A,B), TE-e’ time interval (Table 3; Figure 1, Figure 3 and Figure 10A,B), color M-mode early-diastolic flow propagation velocity (Vp) (Table 3; Figure 1, Figure 3 and Figure 10C), and peak pulmonary regurgitation end-diastolic (PRED) velocity [1] (Table 3; Figure 1, Figure 3 and Figure 10D).
Table 3. Main secondary/supplemental echocardiographic parameters for assessing LV diastolic function [1,2,3].
Figure 9. An example of Valsalva maneuver performing in the presence of normal (A) and pseudonormal (B) transmitral pattern, respectively (see text, tables, and references).
Figure 10. An example of TE-e’ time interval [TE (A) and Te’ (B) measurement], Vp (C), and PREDV1 (D) assessment. PREDV, peak pulmonary regurgitation end-diastolic velocity (measured in m/s); TE, TI between ECG peak R-wave and transmitral E-wave onset (measured in ms); Te’, TI between ECG peak R-wave and TDI e’-wave onset (measured in ms); TE-e’, Te’ minus TE (measured in ms); TDI, tissue Doppler imaging; TI, time interval; Vp, color M-mode early-diastolic flow propagation velocity (measured in cm/s) (see text, tables, and references).
Secondary/supplemental parameters are potentially helpful in diagnosing LV diastolic dysfunction [1]; however, they should be considered in a multiparametric evaluation context due to a number of limitations mainly related to their effective feasibility and reproducibility in routine clinical practice [1]. Their adequate selection is crucial, particularly if significant comorbidities are present, potentially making the measurements misleading (e.g., PRED velocity in the presence of pulmonary disease) [1] (Table 3; Figure 1 and Figure 10A–D).

5. Advanced Techniques for LV Diastolic Function Assessment

Advanced parameters mainly comprise some strain/strain-derived (and AI-assisted, if available) techniques, including LA strain (Table 4; Figure 1, Figure 2, Figure 3 and Figure 11) and (possibly) LV myocardial work (MW) indices [1,6,16] (Table 4; Figure 1 and Figure 12A,B). Additionally, a new ultrasound-based technique has recently been proposed to detect myocardial stiffness in the presence of diastolic dysfunction—cardiac time-harmonic elastography (THE) [25].
Table 4. Main advanced echocardiographic techniques for assessing LV diastolic function [1,6,15,16,25].
Figure 11. An example of LA function evaluation by LA strain technique, assessed from 2D apical four-chamber (above) and two-chamber (below) views. In light of current recommendations, particularly, biplane LARS represents an important diastolic parameter. Note: 2D, two-dimensional; LA, left atrium/atrial; LARS, LA reservoir strain (peak atrial longitudinal strain) (see text, tables, and references).
Figure 12. LV function evaluation by MW (A) compared with GLS (B), in the presence of grade 1 LV diastolic dysfunction and preserved LV EF. In this example, a gradient between basal and apical segments in decreasing longitudinal function is more evident when evaluated by strain-derived MW analysis (whose “bull’s eye” plot looks like an “apical sparing” plot) (A), in comparison with GLS (B). BP, blood pressure; EF, ejection fraction; GCW, global constructive work; GLS, global longitudinal strain; GWE, global work efficiency; GWI, global work index; GWW, global wasted work; LV, left ventricle/ventricular; MW, myocardial work (see text, tables, and references).

5.1. LA Strain

Although not included in the primary/secondary parameters, in light of the recent recommendations, two-dimensional LA strain has become one of the most important criteria for detecting LV diastolic dysfunction [1] (Table 4; Figure 1, Figure 2, Figure 3 and Figure 11). Effectively, LA strain is generally feasible and reproducible, as well as adding important prognostic and predictive value [1].
A number of recent studies have confirmed the added value of two-dimensional LA strain in order to improve diastole-related risk stratification, particularly in the presence of preserved LV EF and sinus rhythm [26,27,28]. Mainly, LA reservoir strain (LARS) enhanced risk stratification [26,27,28], and the ratio of E/e’ and LARS has been proposed to measure LA stiffness and better characterize LA performance [29].
Nonetheless, a number of limitations should be considered [1]. Particularly, some concerns associated with age/load dependency, arrhythmias/bundle branch block (R-R gating may be inaccurate), particular anatomical conditions (e.g., mobile atrial septum, thin-walled left atrium, and mitral annular calcification), significant mitral regurgitation, and history of heart transplantation have been pointed out [1]. Moreover, adequate operator skills, a good ultrasound window (chest-shape dependency should be considered), inter-vendor/inter-software variability, and dedicated software package availability must be mentioned [1,6,24].
In a single-center study enrolling both 72 subjects with metabolic syndrome and 34 healthy volunteers, four-dimensional LA strain has been mentioned for successfully contributing to diastolic function evaluation [30]. To note, a number of other limitations has been pointed out, including the lack of specific threshold values for definition/validation in association with the LV diastolic dysfunction group, as well as the unclear relationship between LA functional changes and disease progression/medication administration [30]. In addition, as the ratio of 3D-measured LA volume index to TDI-derived a’ velocity at the median mitral annulus, LA volumetric/mechanical coupling index (LACI) has recently been proposed for assessing LA performance in this field [31,32]. Notably, many of the above-mentioned limitations remain, also comprehending its challenging usefulness associated with load dependency (LACI includes an LA booster function, thus LACI is influenced by conduit function as well), arrhythmias (e.g., atrial fibrillation and/or absence of a regular rhythm), atrio-ventricular geometry changes that may affect LACI measurements, and possible pulmonary hypertension-related factors [31,32].

5.2. LV MW

LV MW is a relatively recent GLS-derived parameter for assessing LV function [6,16,33]. By adding arterial pressure measurement to GLS, LV MW is born to reduce the (after)load-dependency limitations of LV GLS as well [16,33]. Although not yet introduced in current diastolic assessment guidelines [1], in light of the recent literature, the potential added value of LV MW has been mentioned in this field [34,35,36] (Table 4; Figure 1 and Figure 12A,B).
As for LV GLS [1], taking into account the above-mentioned considerations, the potential MW contribution may be “indirect” for assessing LV diastolic function. Chilingaryan et al. [34] recently studied 215 subjects (5 patients were excluded due to myocardial infarction; mean age, 73 ± 8 years; 63% women; follow-up, 3 years; two experienced echocardiographers performed the echocardiographic exams) with HFpEF and preclinical diastolic dysfunction. The authors [34] showed that LV global constructive work (GCW) predicts EF decline (not related to baseline EF values) in those patients, possibly because GCW reflects LV endocardial constructive shortening in association with afterload. A recent prospective case-control study [35] assessed 133 women receiving anthracycline-based chemotherapy compared to a control group of 65 age-matched healthy women (mean age, 52 ± 12 and 51 ± 6 years, respectively; p-value = 0.263). The chemotherapy group was subsequently subdivided into two groups, namely a chemotherapy-related cardiac dysfunction group and a chemotherapy-related cardiac dysfunction-free group, including 37 and 88 women, respectively [35]. In particular, in the logistic regression analysis, the global work index (GWI) (p-value < 0.001) and GCW (p-value = 0.003) were shown as significant predictors of chemotherapy-related cardiac dysfunction, as well as diastolic stress echocardiography-related peak TR velocity (p-value < 0.001), Troponin (p-value < 0.001), NT-proBNP (p-value < 0.001), LV EF (p-value = 0.021), and GLS (p-value < 0.001) [35]. Notably, several limitations were pointed out, including the single-center design, the small number of subjects developing chemotherapy-related cardiac dysfunction (limiting power for statistical analyses), the short 12-month follow-up duration, subjects with a suboptimal acoustic window (e.g., due to obesity or breast surgery) were excluded, and, importantly, a single experienced operator performed the GLS/MW analyses and diastolic stress echocardiography (not reflecting real-world/multicenter conditions) [35]. Moreover, Jasaityte et al. [36] included 224 women (115 normotensive women versus 69 women with arterial hypertension) in their study, aiming to analyze determinants of MW indices in association with diastolic dysfunction as well; both arterial hypertension and GLS were found to be significantly related to GWI and GCW [36].
Generally, the main limitations of LV MW include the many GLS-related limits, non-invasive arterial pressure measurement-related concerns, and the single available software [6,16,33]. Despite the mentioned GLS and MW intra- and inter-operator reproducibility in the literature [1,15,16], both the GLS and MW analyses were generally and systematically performed by a few expert operators to date [34,35] and, therefore, do not reflect real-world routine clinical practice [6,33].

5.3. Cardiac THE

A new ultrasound-based tool seems available for detecting myocardial stiffness in the presence of diastolic dysfunction—cardiac THE [25]. Enabling the detection and mapping of increased diastolic myocardial stiffness is the main advantage of cardiac THE [25]. Employing both standard medical ultrasound and continuous external vibration for regionally resolved mapping of diastolic shear wave (as a myocardial stiffness indicator), Meyer et al. [25] prospectively selected and studied 109 patients, divided into three groups: 54 healthy controls (47 ± 16 years; 28 men and 26 women; controls versus patients untreated with tafamidis, p-value < 0.001; controls versus patients treated with tafamidis, p-value < 0.001); 10 subjects with moderate LV hypertrophy (70 ± 14 years; five men and five women; controls versus patients with moderate LV hypertrophy, p-value < 0.001; patients with moderate LV hypertrophy versus untreated with tafamidis, p-value = 0.056; patients with moderate LV hypertrophy versus treated with tafamidis, p-value = 0.044); and 45 subjects with wild-type transthyretin amyloidosis (41 men and 4 women), subdivided in 20 patients treated with tafamidis (81 ± 7 years) and 35 untreated subjects (80 ± 7 years; patients untreated versus treated with tafamidis, p-value = 0.696). That single-center prospective study [25] showed cardiac THE as a cost-effective technique, allowing for abnormal myocardial stiffness detection in the presence of diastolic dysfunction. The above-mentioned non-invasive ultrasound-based modality also seemed accurate at greater depths of up to 15 cm, independent of both region selection and body mass index [25]. The limitations include small group sizes, technical limits associated with current restrictions to two-dimensional acquisition/evaluation of diastolic phases only, and THE setup relying on a vibrating bed that is not easily movable to the subject [25].

6. Gaps in the Evidence and Future Perspectives on LV Diastolic Function Assessment

Echocardiographic LV diastolic function and FPs assessment are crucial for routine, comprehensive transthoracic echocardiography in adults in order to evaluate subjects with potential HFpEF as well [1,2,3]. Beyond the “old” LV diastolic function measurements, additional “new” echocardiographic parameters have emerged for optimizing the study of LV diastole [1,37].
Some “old” LV diastolic function parameters remain among the so-called primary techniques, including PW Doppler transmitral inflow and tissue parameters, PW Doppler study on PV inflow, CW Doppler study on TR velocity and IVRT, as well as LAVi [1].
Considering a number of concerns regarding the feasibility and reproducibility, as well as potential comorbidities that may generate misleading results, Valsalva maneuver-related transmitral inflow analysis, TE-e’ time interval, Vp, and PRED velocity are included in the secondary/supplemental parameters [1].
Importantly, in light of recent recommendations, LV GLS actively takes part in the diagnostic echocardiographic workflow [1,37]. Likewise, taking into account the mentioned GLS considerations, LV MW might be a further parameter that can contribute to diagnoses [34,35,36]. Notably, although “reassuring” considerations of GLS and MW intra- and inter-operator reproducibility are mentioned in the literature [1,15,16], both GLS and MW analyses were generally and systematically performed by only a few expert operators to date [34,35], and, therefore, do not reflect real-world routine clinical practice [6,33]. On this topic, real-world multicenter research should be considered for the future [6,33].
Despite not being included in the primary/secondary techniques, in light of recent recommendations, two-dimensional LARS has become one of the most important parameters for LV diastolic dysfunction assessment, enhancing risk stratification as well [1,26,27,28,37]. Also, the ratio of E/e’ and LARS has been proposed to measure LA stiffness and better characterize LA performance [29]. Research on possible promising four-dimensional LA strain is ongoing [30].
Interestingly, besides the ratio of E/e’ and LARS, other parameters seem promising in further refining comprehensive diastolic evaluation and characterization [18,19,20,21,22,31,32]. Effectively, the ratio between LA minimal volume and LV end-diastolic volume (“left atrioventricular coupling index”) may help assess LV diastolic function, being associated with diastolic dysfunction severity and an independent predictor of outcomes in the presence of HF [18,19,20,21,22]. Notwithstanding, left atrioventricular coupling index currently seems to perform worse in the presence of HF with reduced EF, and its prognostic role has mainly been demonstrated in selected subjects with stable HF, sinus rhythm, and in the absence of previous valvular interventions [21]. Additionally, the ratio of 3D-measured LA volume index to TDI-derived a’ velocity at the median mitral annulus (LACI) seems to assess LA performance [31,32]. However, some limitations have been highlighted, noting its challenging usefulness associated with load dependency, arrhythmias (potentially misleading in the absence of a regular rhythm), possible atrio-ventricular geometry changes, and pulmonary hypertension-related concerns [31,32].
Furthermore, cardiac THE represents a potential diagnostic tool for detecting myocardial stiffness in the presence of diastolic dysfunction [25]. Notwithstanding, further studies are needed to better explore this ultrasound-based modality [25].
To date, echocardiographic multiparametric diastolic evaluation seems advisable, employing as many “old and new” measurements as possible—associated with their adequate selection related to the patients’ comorbidities—in order to increase the advantages of the diastolic parameters and possibly minimize their limitations [1]. In particular, with respect to strain and strain-derived techniques, the wide overlap of standard deviations between groups at the population level can make the application of a precise physiological meaning to each individual value in each single subject challenging [6,33]. Moreover, the role of AI-assisted echocardiographic modalities is becoming increasingly important in this field as well, despite a number of persisting AI-related concerns, including interpretability/transparency of AI algorithms and the still-important need for operator supervision of AI-assisted measurements [1,6,7,8,9,10,11,12,13,33].
Taking into account the current considerable number of echocardiographic measurements to perform and describe in the report, the timing of optimal echocardiography performance and reporting should be adequately adapted to the actual technical needs and real-life routine clinical practice [38,39,40]. In order to speed up final reporting, it is possible that AI-assisted dedicated software may be considered in the future [38,39,40].
Importantly, contextual clinical and possible multimodality assessments—including both biomarkers (such as natriuretic peptides) and additional instrumental tools (e.g., cardiac magnetic resonance, nuclear imaging, and invasive hemodynamic evaluation)—should be included in the diagnostic workflow when indicated, in order to enable a more individualized approach [1,37].

7. Conclusions

For accurate diastolic function assessment, to date, many (possibly AI-assisted) measurements have solid evidence of both diagnostic and prognostic efficacy, while other parameters require more evidence and further developments [1,2,3,5,6,8,9,10,11,12,13,15,16,17,23,25,30,37].
The “old” (mainly) Doppler ultrasound-based parameters mostly require both the optimal collaboration of the patient/s and the absence of significant comorbidities that potentially make some parameters misleading (e.g., PRED velocity in the presence of pulmonary disease) [1].
The “new” (mainly) strain-based parameters also require a higher ultrasound window quality, and are more challenging in the presence of some anatomical conditions (e.g., mobile atrial septum, thin-walled left atrium, mitral annular calcification, and particular chest shapes) [1,6,24,33]. Moreover, other factors should be considered, including the inter-vendor/inter-software variability, dedicated software package availability, as well as greater difficulty in performing strain-based measurements in the presence of a larger spectrum of arrhythmias [1,6,33].
In conclusion, echocardiographic multiparametric diastolic evaluation and grading is advisable, using as many “old and new” measurements as possible—associated with their adequate selection related to the patients’ comorbidities—aiming to cumulatively increase the advantages of diastolic parameters and possibly minimize their limitations [1,2,3,6,33]. Taking into account the current considerable number of echocardiographic measurements to perform and describe, the timing of optimal echocardiography performance and reporting should be adequately adapted to the actual technical needs and real-life routine clinical practice, and AI-assisted dedicated software may be considered in next future in order to speed up the final reporting [38,39,40]. Notably, contextual clinical and (if needed) multimodality assessment should be included in the diagnostic workflow, aiming to enable a more individualized approach [1,37].

Author Contributions

Conceptualization, L.D. and G.L.N.; data curation, L.D. and G.L.N.; formal analysis, L.D. and G.L.N.; investigation, L.D. and G.L.N.; methodology, L.D. and G.L.N.; project administration, L.D. and G.L.N.; resources, L.D. and G.L.N.; software, L.D. and G.L.N.; supervision, L.D. and G.L.N.; validation, L.D. and G.L.N.; visualization, L.D. and G.L.N.; writing—original draft, L.D. and G.L.N.; writing—review and editing, L.D. and G.L.N. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Data Availability Statement

The data presented in this study are available upon reasonable request from the corresponding author due to privacy.

Conflicts of Interest

The authors declare no conflicts of interest.

References

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