Quantification of mitral regurgitation using transthoracic echocardiography and cardiac magnetic resonance imaging

Both Transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) have well-established role in mitral regurgitation (MR) quantification for optimal management strategy. We assessed the correlation between TTE and CMR in the quantification of MR. Participants with isolatedMR and echocardiographicmitral regurgitant volume (RVol)≥ 30mL/beat were included. A consecutive sampleof 30participants (Meanage52.7± 19.3 years, 50%males)was selected and referred for indirect and direct CMR quantification of mitral RVol. There was a statistically significant strong positive correlationbetween theechocardiographic and indirectCMRquantification of the mitral RVol (r = 0.753, P< 0.001) and a statistically significant moderate positive correlation between the echocardiographic and direct CMR quantification of the mitral RVol (r = 0.530, P< 0.003). The inter-observer reliability of theMR grade between TTE and CMR showeda statistically significantmoderate agreement (κ =0.502, P= 0.0001) when the observers used the echocardiographic mitral RVol for grading ofMR.On the other hand, the inter-observer reliability of theMRgradebetweenTTEandCMRshowedastatistically significant faint agreement (κ = 0.251, P = 0.024) when the observers used the echocardiographic regurgitant fraction (RF) for grading of MR. The positive reciprocal relationship between the CMR and the TTE highlights the potential role of the CMR as a concomitant imaging tool for quantification of the mitral RVol and grading of isolated MR, especially with limited or inconclusive TTE studies. This will enhance themanagement strategy and improve outcomes.


Introduction
Mitral regurgitation (MR) is a major cause of morbidity and mortality affecting 38,270 persons per 1 million US adult population [1]. Subgroup analysis of the European registry of MR (EuMiClip) data showed a 5.2% prevalence of significant MR and 70% of patients with severe primary MR had a class I indication for surgery [2]. Transthoracic echocardiography (TTE) is the standard approach for the assessment of MR. Despite its numerous technical and non-technical limitations, TTE has been recommended by the American Society of Echocardiography for the quantification of MR [3].
Cardiac magnetic resonance (CMR) is a favored diagnostic imaging technique for valvular heart disease due to its numerous features as non-ionizing radiation, excellent imaging quality, unlimited scan widows with high accuracy and reproducibility, and tissue diagnosis [4]. We wanted to evaluate the correlation between TTE and CMR in the quantification of MR and explore their complementary use for enhancing diagnostic accuracy and improving patient outcomes.

Study design
Our study was a 1-year cross-sectional, open-labeled, nonrandomized, single cohort study conducted at a single cardiac center in a tertiary care hospital. Investigators weren't blinded to the study group. The study design was approved by the hospital ethics committee review board, all participants signed written informed consents, study procedures were carried out following the Code of Ethics of the World Medical Association (Declaration of Helsinki), all information/images were anonymized, and the privacy rights of the study participants were observed diligently.

Study participants
Study participants were patients referred to the cardiology department. They were subjected to history taking and data collection for age, gender, risk factors especially hypertension, diabetes mellitus (DM), chronic kidney disease, coronary artery disease, smoking and hyperlipidemia, nature and course of ischemic, pulmonary congestion and low cardiac output symptoms, and comprehensive clinical examination.

Study procedures
Thirty eligible participants were enrolled, consecutively assigned and allocated in a single cohort, and underwent TTE using Phillips EPIQ 7 ultrasound system for cardiology equipped with xMATRIX transducer (X5-1). Data documented with TTE included jet dimensions, vena contracta, mitral regurgitant volume (RVol) quantification by proximal isovelocity surface area (Echo_RVol), effective regurgitant orifice area, mitral regurgitant fraction (RF) deter-  The enrolled study participants underwent cardiac magnetic resonance (CMR) within one week for quantification of MR using Siemens Magnetom Aera 1.5T magnetic resonance imaging scanner. Data documented with CMR include indirect quantification of mitral RVol by measuring the difference between left and right ventricle stroke volumes (CMR_RVol 1 ) and direct quantification of mitral RVol by phase-contrast velocity mapping (CMR_RVol 2 ) (Table 2) ( Fig. 1) [6].

End points
The study evaluated the correlation between Echo_Rvol and CMR_RVol 1 , and the correlation between Echo_RVol and CMR_RVol 2 . Secondary objectives included assessment of the inter-observer reliability of the MR grade between TTE and CMR.

Statistical analysis
The echocardiographic and CMR assessment outcomes were coded, and the data was analyzed with the Statistical Package for the Social Sciences software for MAC (SPSS®) version 26. Quantitative (continuous) data was expressed as means and standard deviations, while qualitative (categorial) data was expressed as medians and ranges. Parametrically distributed quantitative variables were compared with the Independent two-tailed t-test and correlated with Pearson's Correlation Coefficient, respectively. Pearson's Correlation Coefficient (r) value was interpreted as follows: 1 means perfect correlation, 0.75-1.0 is strong correlation, 0.50-0.75 is moderate correlation, 0.25-0.5 is weak correlation, and < 0.25 means no relationship. The intraclass correlation coefficient (ICC), two-way random model and absolute agreement type were used for comparison between quantitative measurements. The scale of ICC ranges from 0 to 1 where 1 represents perfect reliability with no measurement error and 0 represents no reliability. ICC Value < 0.5 indicates poor reliability, 0.5-0.75 indicates moderate reliability, 0.75-0.9 indicates good reliability and greater than 0.90 indicates excellent reliability [7]. Bland-Altman plot was used for the evaluation of bias between the means of the two modalities within 95% limits of agreement [8]. For categorial agreement, Cohen's kappa coefficient (κ) was used. Kappa values ≤ 0 means no agreement, 0.01-0.20 means none to slight agreement, 0.21-0.40 means fair agreement, 0.41-0.60 means moderate agreement, 0.61-0.80 means substantial agreement, and 0.81-1.00 means almost perfect agreement [9]. The confidence interval was set to 95% and the margin of error accepted was set to 5%. Any comparison considered statistically significant was at P < 0.05 or less.  Values are mean ± SD or N and (%).

Study participants and procedures
We recruited 30 patients from one hospital in one country from January 2019 through December 2019. The study group was balanced with regards to baseline characteristics and risk factors. The key sociodemographic feature of enrolled participants was equal gender representation (Mean age 52.7 ± 19.3 years, 50% males, 50% females). All enrolled participants completed the study and there were no withdrawals.

Mitral regurgitation grade
The inter-observer reliability of the MR grade between TTE and CMR was seen in 20 (66.4%) patients showing statistically significant moderate agreement (κ = 0.502, P = 0.0001) when the observers used Echo_RVol for grading of MR (Table 6, Fig. 5), while the inter-observer reliability of the MR grade between TTE and CMR was seen in 15 (50%) patients showing statistically significant faint agreement (κ = 0.251, P = 0.024) when the observers used Echo_RF for grading of MR (Table 7, Fig. 6).

Discussion
Mitral regurgitation (MR) is a major cause of morbidity and mortality worldwide. Transthoracic echocardiography (TTE) is the standard approach for assessment of MR.
Cardiac Magnetic Resonance (CMR) is a favored diagnostic imaging technique for valvular heart disease. We hypothesized that integration of TTE and CMR will enhance the diagnostic accuracy of MR and improve patient outcomes. We wanted to evaluate the correlation between TTE and CMR in    indirect quantification of MR, but the integrated assessment where regurgitant fraction (RF) was used for grading by TTE minimized the agreement between echocardiography and CMR [10]. Another study by Uretsky S, et al. concluded that the grading of MR severity had a significant moderate agreement between TTE and CMR in the overall cohort (r = 0.6; P < 0.0001) and a significant fair correlation between TTE and CMR in the subset of patients sent for mitral valve surgery (r = 0.4; P = 0.01). The post-surgical left ventricle reverse remodeling quantified by CMR had a significant strong correlation with the MR severity when assessed by MRI (r = 0.85; P < 0.0001) and non-significant poor correlation with the echocardiographic MR severity (r = 0.32; P = 0.1) [11]. The American society of echocardiography has when assessed by TTE). Possible reasons for underestimation of the RVol by CMR include technical limitations of the CMR which led to underrepresentation of patients with moderate, moderate-severe, and severe MR, respiratory and electrical gating artifacts, and/or lower temporal resolution of the CMR flow measurement (25-45 ms) compared to the continuous wave doppler echocardiography (2 ms) which led to quantification error of the high-velocity, short duration MR jets [12]. The time-resolved multidimensional velocity encoded flow CMR (4D flow) has better quantification of the MR irrespective of the direction and/or the number of jets as the 4D can measure the jet flow with high spatial resolution in x-, y-, and z-directions simultaneously [4].

Strengths and limitations
Our study didn't have missing data allowing robust perprotocol analysis, the investigators who analyzed and reported the CMR assessment outcomes were blinded to the participants' clinical data and TTE results, and a second investigator blinded to the CMR measurements reported by the first investigator repeated them at a different time interval to evaluate the inter-observer reproducibility. On the other hand, the study has important limitations. It was a single centered study with small sample size. Being a cross-sectional study with a lack of lengthy follow up didn't allow us to in-vestigate the chronological relationship between the TTE results, the CMR measurements, and the clinically driven outcomes.

Conclusions and recommendations
In our study, the positive correlation between the TTE and the CMR in quantification of mitral RVol highlights the potential role of CMR as a complementary imaging tool to TTE, especially in limited or inconclusive TTE studies. The RF by CMR is more accessible and reproducible, unlike the challenging Echo_RF. This unique feature of CMR leads to better grading and classification of MR which enhances MR management strategy and may improve patients' cardiovascular outcomes. Large prospective studies are warranted to improve the sensitivity and accuracy of the phase-contrast velocity mapping and compare CMR vs TTE regarding the measurement of cardiovascular clinical outcomes in patients with valvular heart disease, especially in asymptomatic MR patients who do not have Class I indications for surgery.

Author contributions
WT did the patients recruitment, reviwed, analysed, interpreted the patient data and writing the manuscript. KA reviewed and approved the study proctol, TM helped in writing and reviewing the manuscript. HE has a major contributor in writing and reviewing the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate
Approved by Research and Ethical committee.