Clinical Significance and Prognostic Value of Novel Echocardiographic Index for the Severity of Mitral Regurgitation

Abstract

Background: Recently, the left ventricular early inflow-outflow index (LVEIO), calculated by dividing mitral E-wave velocity by the left ventricular outflow velocity time integral, has been proposed as a simple method for evaluating mitral regurgitation (MR). This study determined the optimal LVEIO threshold to assess severe MR with different etiologies and assessed its prognostic value.

Methods and Results: The records of 18,692 consecutive patients who underwent echocardiography were reviewed. MR was classified into 4 groups: Grade 0/1, no, trivial, or mild MR; Grade 2, moderate MR; Grade 3, moderate to severe MR; and Grade 4, severe MR. The mean (±SD) LVEIO of Grades 0/1, 2, 3, and 4 was 3.6±1.4, 6.0±2.5, 7.4±3.1, and 9.5±2.8, respectively. An optimal LVEIO threshold of 5.4 was determined to distinguish moderate to severe or severe MR from non-severe MR (sensitivity 84%, specificity 91%). Kaplan-Meier survival analysis revealed high mortality in the group with LVEIO ≥5.4 (P=0.009, hazard ratio 1.833). This was found only in primary MR when separate analyses were performed according to etiology. Multivariate analysis revealed that LVEIO was an independent predictor for all-cause death only in primary MR.

Conclusions: Using appropriate thresholds, LVEIO is a simple and useful method to diagnose severe MR regardless of etiology. LVEIO can also be useful for predicting prognosis in primary MR.

Mitral regurgitation (MR) is a common valvular heart disease defined as the leakage of blood from the left ventricle into the left atrium. Mild MR is often present even in healthy subjects, but significant MR is also a common valvular heart disease in the general population. Epidemiologic studies have shown that moderate to severe MR is associated with cardiac remodeling or dysfunction, as well as with increased mortality.¹ Morbidity also increases if MR is present in older patients.^2,3 Thus, it is important to assess MR in individual subjects. Echocardiography plays a key role in the detection of MR, as well as in the assessment of the underlying mechanism and, thus, in decisions regarding the therapeutic for MR. The severity of MR is assessed as the proximal isovelocity surface area (PISA) and/or using volumetric methods in a quantitative manner. The PISA method is useful only in certain situations: (1) hemispheric symmetry of the shape of PISA; (2) flat orifice; (3) central and single jets; and (4) unchangeable geometry of PISA.^4,5 Conversely, the volumetric method may be useful even in the presence of multiple jets, but either method is time consuming with some anatomical difficulties and limitations.^6,7 In particular, the volumetric method is required to measure the diameter of the left ventricular (LV) outflow tract and mitral valve annular diameter to calculate total and systemic stroke volumes (SV), and the determination of these parameters is not necessarily easy. Thus, a simple and easy approach, if available, would be valuable in many circumstances. Recently, Lee et al proposed using the LV early inflow-outflow index (LVEIO), calculated by dividing the mitral E-wave velocity by the LV outflow velocity time integral (LVOT VTI), to assess severe MR.⁸ Although those authors showed a good correlation in the severity of MR between the echocardiographic gold standard and LVEIO, they did not study the factors affecting the correlation well. In particularly, LV remodeling and systolic dysfunction, individually and together, are likely to induce MR, and it is important to know whether they may affect LVEIO. Thus, in the present study we assessed whether the correlation between MR severity and LVEIO is affected by the etiology of MR and/or LV function. In addition, we also investigated whether LVEIO may reflect the prognosis in patients with MR.

Methods

Study Population

We retrospectively analyzed the results of 26,456 transthoracic echocardiograms that had been routinely performed at Hyogo College of Medicine from February 25, 2013 to May 15, 2015 (Figure 1A). Exclusion criteria were moderate or severe aortic valve regurgitation (n=350), mitral stenosis of any degree (n=80), prior mitral valve surgery (n=358), congenital heart diseases (n=583), LV assist device (n=30), or atrial arrhythmias (n=3,666). LV inflow or outflow Doppler recordings were inadequate or missing in 2,697 echocardiogram studies, and these records were excluded. Thus, the final study cohort consisted of 18,692 patients. The study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Hyogo College of Medicine (Reference no. 2755). Because only routinely collected echocardiographic data and other clinical data were used in this study, the requirement for informed consent was waived.

Figure 1.

(A) Study population. LV, left ventricle. (B) Measurements of left ventricular early inflow-outflow (LVEIO). LVOT VTI, left ventricular outflow tract velocity time integral.

The outcome event was predefined as all-cause death. The outcome was evaluated based on the medical records and, for those patients who did not visit the hospital regularly, was decided by a patient’s condition on the last consultation day.

Echocardiography

Echocardiography examinations were performed using an IE-33, CX50 (Philips Healthcare, Amsterdam, Netherlands), Artida, Aplio300 (Canon Medical System Co., Tochigi, Japan), or F75 (Hitachi-Aloka Medical, Tokyo, Japan). LV ejection fraction (LVEF) was calculated using Teichholz’s formula in patients without LV segmental asynergy or deformation. In patients with LV segmental asynergy or deformation, apical 4- and 2-chamber 2-dimensional echo views and the modified Simpson’s method were used. The parasternal long-axis view was used to determine LV end-diastolic diameter, LV end-systolic diameter, and left atrial (LA) diameter.⁹ The LA volume index was determined using the modified Simpson’s method in the apical 4- and 2-chamber views. Pulsed wave Doppler echocardiography was used to measure the transmitral E-wave, A-wave, and the LVOT VTI according to the American Society of Echocardiography (ASE) guidelines.¹⁰

The severity of MR was assessed using the PISA or volumetric method according to the ASE and European Association of Echocardiography guidelines.^6,11 PISA was measured in the 4-chamber view with color Doppler in which the flow convergence region had a hemispheric shape and the color baseline was shifted to achieve an aliasing velocity of approximately 35 cm/s in the direction of regurgitant flow. The effective regurgitant orifice area (EROA) was calculated using the following formula:

EROA=(2πr²·V_a)/V_max

where r is the PISA radius, V_a is the aliasing velocity of the proximal flow convergence, and V_max is the peak velocity of the mitral regurgitant jet measured by continuous wave Doppler.^12–14 The volumetric method was used in cases with multiple jets or in cases in which the PISA method was not applicable. Regurgitation volume (RVol) was calculated as the difference in SV between the LVOT and the mitral valve determined by the volumetric method. EROA was calculated by the PISA method, and RVol and the regurgitant fraction (RF) were calculated by the volumetric method. The severity of MR was classified into four groups: Group 0/1, no, trivial, or mild MR; Grade 2, mild to moderate or moderate MR; Grade 3, moderate to severe MR; and Grade 4, severe MR. “Moderate to severe” means that some quantitative values were moderate, whereas others were severe. LVEIO was calculated by dividing the mitral E-wave velocity by the LVOT VTI (Figure 1B).

Furthermore, medical records and echocardiographic images were reviewed to determine the detailed etiology of MR, as either primary (degenerative) or secondary (functional), following the ASE guidelines.^5,15,16

Statistical Analysis

Data are presented as the mean±SD or as the median with interquartile range. Categorical data are presented as absolute numbers or percentages. Statistical analyses were performed using t-tests for normally distributed parameters, the Mann-Whitney U-test for parameters with a skewed distribution, and the Chi-squared test for appropriate comparisons. The Spearman method was used to evaluate linear correlations.

The diagnostic performance of LVEIO was assessed by receiver operating characteristic (ROC) curve analysis to calculate the cut-off value for determining moderate to severe or severe MR. The cut-off value was chosen to maximize the (sensitivity+(1−specificity)) value. Multivariable logistic analysis was used to investigate parameters associated with MR severity, including age, sex, LVEF, and LVEIO. Kaplan-Meier survival estimates and a log-rank test were used to assess prognosis in MR patients.

Univariate and multivariate Cox regression analyses were used to determine parameters associated with all-cause death. The multivariate regression model included age, sex, LVEF, LVEIO, and variables with a P-value <0.05 in univariate analysis. P<0.05 was considered statistically significant. Bland-Altman analysis was used to assess intra- and interobserver reproducibility, and 20 patients were randomly selected for this analysis. Lower and upper reproducibility limits were calculated as ±1.96 SD. The results of Bland-Altman analysis are shown in Supplementary Figure 1 and indicate good reliability in E-wave velocity, LVOT VTI, and EROA. Ranges for intra- and interobserver agreement were as follows: from −1.14 to 1.74 and from −0.62 to 1.22, respectively, for E-wave velocity; from −0.29 to 0.31 and from −0.20 to 0.25, respectively, for LVOT VTI; and from −0.05 to 0.04 and from −0.028 to 0.021, respectively, for EROA. Statistical analyses were performed using JMP 10 (SAS Institute, Cary, NC, USA).

Results

The 18,692 patients were classified into different grades according to the severity of MR: 17,960 Grade 0/1 (no, trivial, or mild MR), 600 Grade 2 (mild to moderate or moderate MR), 82 Grade 3 (moderate to severe MR) and 50 Grade 4 (severe MR). The characteristics and echocardiographic measurements for patients according to MR severity are provided in Table 1. LVEF was lowest in patients with Grade 2 MR, whereas E-wave velocity and EROA were greater in patients with higher MR grades. The mean LVEIO of the Grade 0/1, Grade 2, Grade 3 and Grade 4 groups was 3.6 ±1.4, 6.0±2.5, 7.4±3.1, and 9.5±2.8, respectively. There was a moderate correlation between LVEIO and RF (r=0.55, P<0.0001; Figure 2), but no correlation between LVEIO and RVol (r=0.32, P<0.0001) or EROA (r=0.48, P<0.0001). For the diagnosis of moderate to severe or severe MR, the area under the curve (AUC) for LVEIO, as determined by ROC analysis, was 0.93 (Table 2). The optimal threshold of LVEIO to distinguish MR Grades 3 and 4 from MR Grades 0/1 and 2 was 5.4 (sensitivity 84%, specificity 91%). In this analysis, we regarded Grades 3 and 4 as severe simply because both Grades 4 and 3 are associated with a poor prognosis.¹⁷

Table 1. Baseline Demographic and Echocardiographic Characteristics of Study Patients According to Mitral Regurgitation Grade

	MR grade
	0/1 (n=17,960)	2 (n=600)	3 (n=82)	4 (n=50)
Age (years)	67 [55–76]	72 [62–78]*	69 [60–76]†	70 [58–77]
Male (%)	56	52*	59*,†	50*,†,‡
LVEF (%)	67 [60–73]	44 [30–68]*	64 [36–73]*,†	73 [37–79]†
LVEF <50% (%)	13	56*	37*,†	34*,†,‡
LAVI (mL/m2)	32±12	55±18*	66±29*,†	63±18*,†
E-wave (cm/s)	70±22	96±28*	113±22*,†	147±26*,†,‡
LVOT VTI (cm)	20.0±5.0	17.5±6.3*	17.3±5.6*	16.2±3.6*
LVEIO	3.6±1.4	6.0±2.5*	7.4±3.1*,†	9.5±2.8*,†,‡
EROA (cm2)	0.13±0.05	0.25±0.08*	0.36±0.08*,†	0.49±0.17*,†
RF (%)	26±9	42±9*	51±8*,†	58±6*,†,‡
RVol (mL)	23±13	42±11*	63±11*,†	74±18*,†,‡

Values are given as the mean±SD (range), n (%), or median [interquartile range]. *P<0.05 compared with MR Grade 2; ^†P<0.05 compared with MR Grade 3; *P<0.05 compared with MR Grade 0/1, ^†P<0.05 compared with MR Grade 2, ^‡P<0.05 compared with MR Grade 3. EROA, effective regurgitant orifice area; LAVI, left atrial volume index; LVEF, left ventricular ejection fraction; LVEIO, left ventricular early inflow-outflow index; LVOT VTI, left ventricular outflow velocity time integral; MR, mitral regurgitation; RF, regurgitant fraction; RVol, regurgitant volume.

Figure 2.

Correlation between left ventricular early inflow-outflow (LVEIO) and (A) regurgitant fraction (RF) and (B) effective regurgitant orifice area (EROA).

Table 2. Receiver Operating Characteristic Curve Analysis Defining the Usefulness of Echocardiographic Parameters for Detecting MR Grade 3 or 4

	Total (n=18,692)			Age (years)		LVEF
	AUC	Cut-off	Sp (%)/ Sn (%)	<50 (n=3,522) AUC	≥50 (n=15,170) AUC	Reduced (n=2,786) AUC	Preserved (n=15,906) AUC
LVEIO	0.93	5.4	90/85	0.94	0.94	0.94	0.92
E-wave	0.94	93	85/89	0.85	0.93	0.93	0.93
PISA method
EROA	0.95	0.25	84/98	0.87	0.97	0.96	0.96
Volumetric method
RF	0.92	44	79/91	0.95	0.92	0.93	0.96

AUC, area under the curve; Sn, sensitivity; Sp, specificity. Other abbreviations as in Table 1.

The diagnostic value of LVEIO was assessed in relation to age and LVEF. Most patients in this study (n=15,170; 81%) were aged ≥50 years; the remainder (n=3,522; 19%) were <50 years of age. LVEIO and E-wave velocity were weakly correlated with age (r=0.30 [P<0.0001] and r=0.22 [P<0.0001], respectively). In patients <50 years of age, the optimal LVEIO threshold to detect MR Grades 3 or 4 was 5.1, and there was no difference in the AUC between LVEIO and EROA independent of age (Table 2). LVEF was <50% in 2,786 patients and ≥50% in 15,906 patients. The AUC for detecting Grade 3 or 4 MR was not different between the LVEF subsets. Age, LVEF, and LVEIO were selected as independent parameters in multivariate logistic analysis for detecting MR Grade 3 or 4, with odds ratios (ORs) of 1.04 (P<0.0001), 1.03 (P <0.0001), and 2.06 (P<0.0001), respectively.

There were 732 patients with MR Grade 2, 3, or 4; 313 patients had primary MR and 419 had secondary MR (Table 3). Mitral valve tethering was the most common mechanism underlying MR among patients with secondary MR. LVEF was lower in patients with secondary MR than in those with primary MR in total and for all grades separately. LVEIO increased with MR grade in patients with primary MR; in addition, among patients with secondary MR, LVEIO was greater in those with MR Grade 3 or 4 than in those with MR Grade 2 (P<0.0001). LVEIO was greater for patients with secondary MR categorized as Grade 2 or 3 than for patients with primary MR (Figure 3), probably reflecting the smaller LVOT VTI in patients with secondary MR. The data LVEIO were similar to the RF data.

Table 3. Demographic and Echocardiographic Variables of Patients With Grade 2–4 MR According to MR Etiology

	Primary MR				Secondary MR
	Total	Grade 2	Grade 3	Grade 4	Total	Grade 2	Grade 3	Grade 4
n (%)	313	224 (72)	55 (18)	34 (11)	419	376 (90)	27 (6)	16 (4)
Demographic data
Age (years)	68±14	68±15	68±10	68±12	69±14	69±14	70±12	68±13
Male (%)	44	41	53	44	60	59	70	59
Echocardiographic data
LAVI	55±23	52±19	66±33*	63±18*	58±17	57±16	67±18*	62±18
LVEF (%)	71 [64–76]	71 [63–75]	71 [64–75]	77*,†[72–80]	33 [25–43]	34 [25–43]	28 [23–37]	34 [27–36]
E-wave (cm/s)	106±33	98±30	114±23*	151±27*,†	98±28	96±27	110±19*	137±21*,†
LVOT VTI (cm)	19.4±4.8	19.7±4.8	19.3±4.9	16.9±3.7*,†	15.9±6.5	16.1±6.7	13.3±4.7*	14.6±3.0
LVEIO	5.8±2.3	5.1±1.6	6.3±2.1*	9.4±3.1*,†	6.9±2.9	6.6±2.7	9.4±3.8*	9.7±2.2*
LVDd (mm)	53±7	52±7	57±5*	55±6*	61±9	61±9	65±9*	65±10
LVDs (mm)	32±8	32±9	34±5	31±7	50±12	50±12	54±10	54±11
EROA (cm2)	0.32±0.13	0.26±0.08	0.36±0.07*	0.53±0.18*,†	0.25±0.10	0.24±0.09	0.35±0.10*	0.40±0.13*
RF (%)	44±9	41±8	49±7*	57±6*,†	45±10	43±9	57±9*	60±7*

Values are given as the mean±SD (range), n (%), or median [interquartile range]. *P<0.05 compared with MR Grade 2; ^†P<0.05 compared with MR Grade 3. LVDd, left ventricular diastolic diameter; LVDs, left ventricular systolic diameter. Other abbreviations as in Table 1.

Figure 3.

Mean left ventricular early inflow-outflow (LVEIO) in patients with primary and secondary mitral regurgitation (MR) according to MR grade. Grade 2, moderate MR; Grade 3, moderate to severe MR; Grade 4, severe MR. *P<0.05 compared with primary MR.

When the clinical course was compared in MR Grade ≥2 patients with an LVEIO of <5.4 vs. an LVEIO of ≥5.4 at a median follow-up of 923 days (n=732), there were 104 deaths, including 42 cardiovascular deaths. Kaplan-Meier survival curve analysis showed that patients with an LVEIO ≥5.4 had higher mortality from all-cause death than those with an LVEIO <5.4 (Figure 4A), whereas there was no association between conventional MR grading and the clinical course (P=0.740 for MR Grade 2 vs. MR Grades 3 and 4). This result did not change when we included surgery for MR in the outcome (Supplementary Figure 2). The association with LVEIO was only observed for primary and not secondary MR when each etiology was analyzed separately (Figure 4B,C). In Cox regression analysis, LVEIO and sex were independently associated with all-cause death in primary MR (Table 4). In secondary MR, sex and LVEF were associated with prognosis.

Figure 4.

Kaplan-Meier curves for (A) total all-cause mortality in 732 patients with Grade 2–4 mitral regurgitation (MR), (B) all-cause death in patients with primary MR, and (C) all-cause death in secondary MR according to left ventricular early inflow-outflow (LVEIO) ≥5.4 and <5.4. Across the entire study cohort (A), patients with an LVEIO ≥5.4 had a worse prognosis than those with an LVEIO <5.4.

Table 4. Univariate and Multivariate Analysis for All-Cause Death

Variables	Univariate			Multivariate
	HR	95% CI	P-value	HR	95% CI	P-value
MR Grades 2–4 (n=732)
Age >50 years	2.26	0.92–5.52	0.0755	2.40	0.98–5.89	0.0567
Sex (female)	0.45	0.30–0.68	0.0002	0.52	0.34–0.79	0.0026
LVEF >50%	2.61	1.70–4.02	<0.0001	2.14	1.37–3.36	0.0009
LVEIO >5.4	1.75	1.15–2.67	0.0098	1.38	0.89–2.14	0.1551
ERO >0.40 cm2	1.89	0.81–4.44	0.1439
LVDd	0.99	0.97–1.01	0.6808
LVDs	1.01	0.99–1.02	0.3180
Primary MR
Age >50 years	1.40	0.33–5.91	0.6454	1.55	0.36–6.65	0.5566
Sex (female)	2.35	1.50–3.69	0.0002	0.35	0.15–0.83	0.0184
LVEF >50%	2.16	0.75–6.26	0.1581	2.14	0.73–6.25	0.1684
LVEIO >5.4	4.49	1.69–11.92	0.0027	4.14	1.55–11.05	0.0048
ERO >0.40 cm2	2.12	0.59–7.54	0.2502
LVDd	0.97	0.91–1.02	0.2420
LVDs	1.00	0.95–1.05	0.8635
Secondary MR
Age >50 years	2.68	0.85–8.44	0.0944	2.11	0.66–6.81	0.2123
Sex (female)	0.59	0.36–0.95	0.0299	0.46	0.28–0.76	0.0028
LVEF >50%	1.91	0.88–4.13	0.1023	3.97	1.53–10.27	0.0047
LVEIO >5.4	1.04	0.65–1.66	0.8758	0.98	0.61–1.61	0.9473
ERO >0.40 cm2	2.82	0.86–9.18	0.0874
LVDd	0.97	0.94–0.99	0.0148	0.99	0.92–1.06	0.7954
LVDs	0.98	0.96–0.998	0.0319	0.95	0.89–1.01	0.1223

CI, confidence interval; ERO, effective regurgitant orifice; HR, hazard ratio. Other abbreviations as in Tables 1,3.

Discussion

The present study demonstrated that LVEIO has diagnostic capability for detecting clinically severe MR using an LVEIO cut-off value of 5.4 regardless of the underlying EF or MR etiology. LVEIO was well correlated with RF, and LVEIO ≥5.4 was associated with a poor clinical course. The cut-off value in this study was lower than that in a previous study.¹⁸ We assume the reason for this difference is the etiology of MR in the study cohort. Rheumatic heart disease was present in more than half the subjects of the previous study,¹⁸ and there was a predisposition for high E-wave velocity with comorbid mitral stenosis.

Although MR severity is determined using color Doppler images clinically in routine examinations, it is subject to gain adjustment, range setting, blood pressure, volume status etc.; therefore, the quantification of MR is important in many situations. However, the reproducibility and accuracy of MR quantitation remain in doubt.¹⁹ Thus, a simple method for the quantitation of LVEIO should be useful in clinical settings.

Effects of Aging

Both aging and LV diastolic function affect E-wave velocity. In the present cohort, E-wave velocity was correlated with age, but the correlation was not as good as reported previously.²⁰ The reason for this is likely that the present cohort included unhealthy people with cardiac diseases with higher E-wave velocity. Thus, we assessed the relationship between aging and LVEIO in our patient cohort, dividing the patients into two groups, those age ≥50 and <50 years. The diagnostic value of LVEIO was unchanged even in those aged <50 years (Table 2).

Effects of LV Function

LVEIO may well increase if LVEF is reduced because reduced LVEF is usually associated with decreased SV, and hence LVOT VTI, and an increase in E-wave velocity because of the secondary increase in LA pressure. Lee et al reported that the discriminatory power of LVEIO for MR Grade 3 or 4 was lower in patients with reduced than preserved LVEF.⁸ However, in that study LVEIO had a better AUC for severe MR than other indices, such as E-wave velocity and EROA.⁸ In the present study, LVEIO was useful in detecting severe MR in patients with reduced LVEF, as well as in those with preserved LVEF. One may think that LVEIO could overestimate the severity of MR in patients with severely reduced LVEF or LVOT VTI. In the present study, LVEIO correlated well with RF but not EROA and RVol. RF may reflect the actual severity of MR regardless of LVEF; therefore, we assumed LVEIO had good discriminatory power regardless LVEF in the present study.

Effects of MR Etiology

Currently, the choice of therapeutic strategy is significantly affected by the etiology of MR. Previous guidelines have recommended different severity criteria depending on MR etiology.²¹ For example, in in primary MR the criteria for severe MR are EROA>0.4, RVol >60 mL, and RF >50%, whereas in secondary MR the criteria are EROA >0.2, RVol >30 mL, and RF >50%. Specifically, the cut-off values differ according to the etiology, except for RF, which has the same cut-off point in the case of both primary and secondary MR. Recently, revised guidelines have recommended that MR severity should be assessed using the same criteria regardless of etiology (i.e., primary or secondary MR).⁵ At the same time, the revised guidelines note that the PISA method may underestimate MR severity due to the elliptical regurgitant orifice in patients with secondary MR. When assessing the severity of MR, the clinical condition and etiology of MR should be considered. The present study demonstrated LVEIO was greater in patients with secondary than primary MR, whereas EROA was smaller in patients with secondary than primary MR. This means that the clinical condition may be severe in patients with secondary MR with reduced LVEF. EROA may underestimate MR severity in patients with secondary MR and reduced LVEF. LVEIO correlated well with RF in the present study, and this is one of the reasons why LVEIO may be used as an estimate of MR severity regardless of MR etiology.

Clinical Course

It is well known that the mortality rate increases with the severity of MR.²² In the present study, LVEIO ≥5.4 was associated with increased all-cause mortality compared with LVEIO <5.4. In addition to MR severity, another 2 factors account for the further increase in LVEIO: (1) a decrease in the forward SV due to associated LV systolic dysfunction; and (2) an increase in E-wave velocity due to associated LV diastolic dysfunction and/or an increase in LA pressure. These factors may also contribute to the LVEIO value in predicting the prognosis of patients with severe MR. The reason for an association between LVEIO and mortality rate only in primary MR is assumed to be the significant effects of various comorbid factors in secondary MR.

Study Limitations

The present study has several limitations. First, we determined an LVEIO of 5.4 as the cut-off value to detect severe MR; however, we did not compare LVEIO with any other established estimate of MR severity (gold standard) such as cardiovascular magnetic resonance imaging or angiographic parameters. Second, RF was not measured in patients with no or obviously trivial MR. When these patients were excluded from the analysis, the AUC from ROC analysis for severe MR was 0.78. We think this is acceptable. Third, a lack of invasive LA pressure data prevents us from studying the mechanism underlying the increase in E-wave velocity in patients with severe MR. Fourth, although all patients were enrolled in a consecutive manner, this study was a single-center retrospective study. Finally, patients with atrial arrhythmias were excluded from the study, but many patients with severe MR have atrial arrhythmias. The LVEIO value in patients with atrial arrhythmias should be investigated in future studies.

Conclusions

LVEIO is a simple and useful method to assess MR severity independent of LVEF or the age of subjects. It also provides useful information about the prognosis in primary MR.

Acknowledgements

The authors thank the echocardiography technicians for collecting data.

Disclosures

T. Masuyama is a member of Circulation Reports ’ Editorial Team.

IRB Information

This study was approved by the Ethics Committee of Hyogo College of Medicine (Reference no. 2755).

Data Availability

The deidentified participant data will not be shared.

Sources of Funding

None.

Supplementary Files

Please find supplementary file(s);

http://dx.doi.org/10.1253/circrep.CR-20-0027

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