Qualitative Assessment of Color M-Mode Signals in the Evaluation of Left Ventricular Diastolic Function: A Proof of Concept Study

Abstract

Objectives:

Although the most recent American Society of Echocardiography (ASE) guidelines are a major step forward in echocardiographic evaluation of diastolic function, the ability to differentiate between normal and abnormal function remains challenging. We aimed to determine whether qualitative assessments of color M-mode flow displays could be a useful parameter in the evaluation of left ventricular (LV) diastolic dysfunction.

Design:

Retrospective observational study.

Setting:

Tertiary care level hospital.

Participants:

The study comprised echocardiographic data from 105 consecutive patients.

Intervention:

None.

Measurements and Main Results:

Patients were allocated into three groups according to the LV diastolic function based on current ASE recommendation guidelines for LV diastolic dysfunction classification: Group I with normal function (n=40); Group II with early relaxation abnormalities (grade I) (n=50) and Group III with elevated left ventricular pressures (grade II) (n=15). Patients with normal diastolic function were younger (45 ± 14 years) than those with diastolic dysfunction (Group II: 64 ± 10 and Group III: 56 ± 15 years) (p<.05). Volumetric echocardiographic parameters and mitral inflow and mitral annulus tissue Doppler imaging measures were significantly different among the three studied groups (p<.05). Interestingly, qualitative assessment of color M-mode flows displayed distinctive signals based on the left ventricle filling properties. Intra- and interobserver variability to determine the reliability of these signals were robust (weighted kappa: 0.84 ± 0.11 and 0.65 ± 0.13, respectively).

Conclusion:

Qualitative assessment of color M-mode flow displays offers simple and reliable information of potential usefulness in the evaluation of LV diastolic function.

INTRODUCTION

Echocardiographic assessment of LV diastolic function is critically important during routine examination of patients with symptoms suggestive of heart failure. Both the American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) published in 2009 specific and comprehensive guidelines to assess diastolic function. [1] However, this can be challenging as LV diastolic dysfunction is the result of a complex interplay of impaired LV relaxation, decreased myocardial compliance, and ultimate elevation of left atrial pressure. [2-4]

Given the relationship to isovolumic pressure decay (Tau), [5] velocity of propagation (Vp) obtained from color M-mode spectral display was one of the proposed methods to evaluate LV diastolic dysfunction in the 2009 ASE/EACVI guidelines [1]. However, it was shortly removed in the 2016 update citing technical difficulties in obtaining accurate measurements and misleading results in patients with elevated LV filling pressures and normal left ventricular ejection fraction (LVEF) [6,7].

Since our laboratory has previously studied color M-mode flow displays in assessing LV diastolic function; [8] we sought to evaluate whether qualitative assessments of color M-mode flow displays may aid in the evaluation of LV diastolic dysfunction -mainly based on strict recommendations suggested in the updated ASE / EACVI guidelines.

METHODS

For this proof of concept study, we included data from 105 consecutive patients obtained from our echocardiographic database that had complete echocardiograms, including color M-mode flow displays obtained from 4-chamber apical views of the LV.

Assessment of LV diastolic function was performed on all patients using strict LV diastolic dysfunction classifications from the latest 2016 ASE/EACVI guidelines. Patient with significant atrial or ventricular ectopy, pacer or defibrillator and significant left-sided valvular disease were excluded given inability to grade severity of diastolic dysfunction based on current guidelines. [7] If tricuspid regurgitation velocity was not measured, remaining criteria was used to classify the severity of the diastolic dysfunction.

The studied population was divided into three groups according to the severity of LV diastolic dysfunction: Group I consisted of 40 patients with normal LV diastolic function; Group II included 50 patients classified as having early relaxation abnormalities (grade I) and Group III was made up of 15 patients with grade II LV diastolic dysfunction. The University of Cincinnati College of Medicine Institutional Review Board Committee approved data collection for this study (protocol number 12061302). No written consent was needed to obtain since this was a retrospective analysis.

Two-dimensional echocardiographic (Vivid 7, GE Medical Systems, Milwaukee, WI) images were digitally acquired with a 1.5/3.1 MHz phased array transducer using standard harmonic imaging, in gently held end-expiration, for subsequent offline analysis using the Acuson Syngo system (V 6.0 Diagnostic Workstation, Siemens, California.). Examinations were performed in accordance with ASE recommendations. [7, 9] For assessment of LV color M-mode flow displays, the color velocity scale was adjusted to produce aliasing in the early main diastolic signal. The cursor was aligned parallel to the inflow between the mitral leaflets at the apical 4-chamber sector plane as previously described. [1,5-7]

To better characterize the potential utility of these qualitative assessments of color M-mode flow displays, we compared our blinded interpretation of these tracings against LV diastolic function assessments based on the 2016 ASE / EACVI guidelines.

Data is represented in mean ± standard deviation. Continuous variables were compared between all groups using one-way analysis of variance assuming equal variances. To evaluate the effects of observational variability on measurements, two independent observers analyzed 10 randomly selected patient studies. An inter-rater agreement statistic Kappa value was calculated to assess the strength of agreement between separate measurements. All statistical analyses were performed using STATA version 14.2 (StataCorp, College Station, Texas). P-values of less than .05 were considered statistically significant.

RESULTS

The echocardiographic data of the study population is depicted in Table 1. Overall, patients with normal diastolic function were younger (45 ± 14 years; p <.001) than those with diastolic dysfunction. Furthermore, patients with grade I LV diastolic dysfunction were the oldest (Group II: 64 ± 10 vs. Group III: 56 ± 15 years; p< 0.001). Gender distribution was almost even among the three groups (Group I: 21 males / 40 patients; Group II: 22 males / 50 patients and Group III: 9 males / 15 patients). There were no differences in terms of body surface area (Group I: 2.0 ± 0.3, Group II: 1.9 ± 0.3, and Group III: 2.0 ± 0.3m²; p >.05).

Table 1.

Echocardiographic data of the study population.

Variables	Group I	Group II	Group III	P-value
LVMI (g/m2)	82 ± 29	103 ± 39	118 ± 44	.003
LAVI (ml/m2)	26 ± 13	30 ± 11	40 ± 12	.001
LVESV (ml)	36 ± 19	33 ± 34	98 ± 67	<.001
LVEDV (ml)	111 ± 35	107 ± 48	165 ± 60	<.001
LVEF (%)	69 ± 10	72 ± 14	46 ± 22	<.001
MA TDI s’ (cm/s)	9 ± 2	8 ± 3	5 ± 1	<.001
MV E (cm/s)	86 ± 27	69 ± 23	113 ± 30	<.001
MV E/A ratio	1.5 ± 0.6	0.9 ± 0.24	1.4 ± 0.4	<.001
MA TDI e’(cm/s)	13 ± 4	8 ± 2	5 ± 2	<.001
MV E/MA TDI e’ ratio	7.4 ± 3.8	9.5 ± 3.9	24 ± 11	<.001

LVMI: left ventricle mass index; LAVI: left atrial volume index; LVESV: left ventricle end-systolic volume; LVEDV: left ventricle end-diastolic volume; LVEF: left ventricle ejection fraction; MA: mitral annulus; TDI: Tissue Doppler imaging; MV: mitral valve.

Two representative color M-mode flow displays for each of the three patient groups are shown in Figure 1. Of notice, a predominant early flow signal (E) with a steep initial/terminal slope as well as a very dim and small non-dominant late diastolic signal (A) characterizes normal diastole. On the other hand, patients with grade I LV diastolic dysfunction have a predominant A wave with almost no E wave. Lastly, two possible variants can be displayed in grade II LV diastolic dysfunction: 1) predominant E over A that might mirror a normal pattern but in contrast to normal LV filling, the upper portion of the early diastolic flow signal will have a shallow rather than a steep final slope; 2) Almost fusion of the two diastolic flow signals later in electrical and mechanical diastole with the same terminal shallow rather than a steep slope of the early diastolic flow signal. All these LV diastolic dysfunction qualitative descriptors were provided to two echocardiographers to obtain both intra and interobserver variability. While the intraobserver variability weighted Kappa value was 0.84 (almost perfect agreement) with a standard error of 0.11 (95% CI: 0.63-1.00); the interobserver variability weighted Kappa value was 0.65 (substantial agreement) with a standard error of 0.13 (95% CI: 0.39-0.90). Overall, these values showed a good agreement between color M-mode signal displays and identification of left ventricular diastolic function assessment based on current ASE / EACVI guidelines.

Figure 1.

Representative color M-mode flow displays (yellow arrows). (A-B) Patients with normal LV diastole. Notice the predominant early flow signal as well as a very dim and small non-dominant late diastolic signal. (C-D) Patients with grade I LV diastolic dysfunction. Notice the minimal early diastolic and predominant late diastolic flow signals, this last with a clear turbulent flow. (E-F) Patients with grade II LV diastolic dysfunction. Notice the two possible variants: 1) predominant E over A that might mirror a normal pattern but in contrast to normal LV filling the upper portion of the early diastolic flow signal will have a shallow rather than a steep final slope (E). 2) Almost fusion of the two diastolic flow signals later in electrical and mechanical diastole with the same terminal shallow rather than a steep slope of the early diastolic flow signal (F).

DISCUSSION

In this proof of concept study, color M-mode flow displays were qualitatively interpreted based on the distribution and intensity of early (E) and late (A) diastolic flow signals without prior knowledge of LV diastolic dysfunction classification. Our results show that color M-mode flow signals have a distinctive pattern for each of the studied groups (normal LV diastolic function, grade I and II LV diastolic dysfunction). Thus, re-emerging as a simple and reliable parameter that is useful in assessing LV diastolic filling behavior.

Comprehensive and precise evaluation of LV diastolic function is of utmost clinical importance, particularly in patients with heart failure and preserved ejection fraction [7, 10, 11] Unfortunately, echocardiographic characterization of LV diastolic dysfunction remains challenging despite recent updates in the ASE / EACVI guidelines. [7] In fact, since accurate characterization of LV diastolic abnormalities cannot be made in up to 15% of patients, the guidelines’ writing group acknowledged the need for realistic expectations regarding LV diastolic function assessment when using these guidelines. [7, 12] Accordingly, they have suggested the use of additional echo-Doppler variables to improve LV diastolic function assessments for such challenging cases. [7] However, in most echocardiography laboratories these variables are not routinely employed as a result of time or expertise constraints. Therefore, a simple variable that can be both acquired easily and reproducible could be of extreme clinical usefulness.

Color M-mode interrogation during diastole allows a visual spatiotemporal representation of the early and late LV diastolic filling. [5-8, 13] Our novel approach took advantage of this high temporal resolution to better characterize diastolic function by color flow. To validate visual assessment of color M-mode flow, we evaluated both intraobserver and interobserver variability and found almost perfect and substantial agreement respectively.

From a mechanistic point of view, in early diastole, after mitral valve opening, LV pressure continues to decrease even when the LV chamber continues to expand. [13] The resultant isovelocity contour created during early LV filling allows for the identification of the flow wave front slope which yields the propagation velocity (Vp) of early LV diastolic filling. [10] Though this quantitative measure was quite useful in differentiating normal from abnormal diastolic function and previously incorporated into the 2009 ASE LV diastolic assessment guidelines; [1] difficulties in measuring the true slope of the early LV diastolic flow propagation color signal led to its eventual demise. However, since qualitative interpretations of color M-mode flows are more practical -as they seem to follow the intrinsic relation that exists between isovolumic pressure decay and LV filling, we attempted to identify characteristic flow displays based on the degree of diastolic dysfunction. Indeed, patients with normal LV diastolic function had a predominant early flow signal as well as a very dim and small non-dominant late diastolic signal. As LV diastolic dysfunction ensues as in patients with grade I, a minimal early diastolic with a rather dominant late diastolic flow signal can be easily identified. Finally, patients with grade II LV diastolic dysfunction either show a color M-mode pattern that mirrors the normal pattern or one in which both diastolic signals are fused together. The hallmark of this type of pattern is that terminal portion of the early diastolic signal is shallow rather than steep.

Some limitations need to be acknowledged. First, the retrospective nature and the small sample size. Second, only patients on sinus rhythm were included in the study and therefore, we cannot extrapolate these results to patients with atrial fibrillation. Third, the lack of right heart hemodynamics variables as well as representative data from patients with restrictive diastolic dysfunction patterns might limit our understanding on the impact of right chambers abnormalities and severe LV systolic dysfunction on these color M-mode flow patterns. Nonetheless, our intent was to prove that a qualitatively assessment of color M-mode flow displays might be of potential usefulness to further evaluate LV diastolic function. Particularly, for those patients that do not fit on current LV diastolic dysfunction classification criteria. Finally, though left atrial inflow propagation rate obtained by color M-mode transesophageal echocardiography (TEE) has been suggested as an index of preload, [14] the utility of color M-mode in TEE remains poorly understood. Thus, studies are warranted to further identify potential applications of color M-mode not just for transthoracic echocardiography but also for elective and intraoperative TEE.

CONCLUSIONS

In this preliminary study, we attempted to revive the potential utility of color M-mode flow displays in the assessment of LV diastolic function from a qualitative approach. Color M-mode flow signals shows a distinctive pattern based on the degree of diastolic dysfunction. A large-scale prospective study is now needed to determine if this qualitative assessment can be useful in patients with atrial fibrillation and valvular abnormalities. Also, its value in distinguishing normal aging from pathologic abnormal LV relaxation as well as usefulness in identifying abnormal LV filling pressures with different cardiomyopathic processes, needs to be further addressed.