• mitral regurgitation
• echocardiography
• transcatheter valve interventions

Secondary mitral regurgitation (MR) is a hot topic of cardiovascular field after two randomised trials of transcatheter edge-to-edge repair in patients with secondary MR—Multicenter Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients with Severe Secondary MR (MITRA-FR) and Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional MR (COAPT).1 2 The trials had similar aims, but in COAPT trial, MitraClip was associated with decreased risk of death and hospitalisation for heart failure, and in MITRA-FR, the intervention was not effectiveness for the prognosis. Many investigators try to clarify the difference between two trials.3 4 One possible explanation is the different cohort study between the two trials. From the standpoints of haemodynamic status, the effective regurgitant orifice area (EROA) can be estimated from left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF) and regurgitant fraction (RF) based on the Gorlin hydraulic orifice equation. For example, in a patient with LVEDV of 230 mL, LVEF of 30% and RF of 50%, EROA can be estimated as around 0.3 cm². If the actual EROA is over the estimated EROA from LVEDV, LVEF and RF, this haemodynamic status is ‘disproportionate MR’. COAPT enrolled a subset of patients who have more MR severity with less LV dysfunction (namely disproportionate MR) compared with MITRA-FR. This is one reason of discrepancy between two trials’ results.5 Moreover, the accuracy of the measurements of regurgitant severity by echocardiography is sometimes unreliable in the secondary MR. For example, the actual mean total stroke volume in the COAPT trial as measured with Doppler was 51 mL, and the regurgitant volume (RV) as measured with the use of the proximal isovelocity surface area (PISA) method was 59 mL. According to these data, calculated RF was over 100% which was unable to explain well about the haemodynamic status in the COAPT trial.6 Thus, we need a better measurement to assess the accurate states of MR in the MitraClip era.

In their Heart manuscript, Kamoen et al 7 evaluated the prognostic utility of a novel measurement of regurgitant severity, average pixel intensity (API) method in a cohort of 231 patients with heart failure and secondary MR. This included patients with a wide range of MR severity (the mean PISA-EROA and PISA-RV were 0.16 cm² and 28 mL) during a median follow-up of 24 months. The applicability of the API method was excellent (98%), which was significantly higher than other MR grading parameters. MR grading with API method was an independent predictor of major adverse cardiac events (adjusted HR: 1.095 per 10 au API rise). Authors concluded the API method may be a valuable measurement for grading secondary MR, which is important for risk stratification and decision-making.

All echocardiographic parameters used to assess MR severity have their advantages and limitations (table 1). The API has advantages including quantitative, single measurement, and avoids geometric assumptions. Moreover, the API method is a simple digital format and can be suitable in the modern era of artificial intelligence of medical imaging.8 On the other hand, there are also some limitations including not applicable in eccentric jet, not valid for multiple jets, errors in tracing the continuous wave envelope and no specific cut-off value. This method should be tested in a multicentre study for the applicability and clinical utility.

What are the clinical implications of the API method? The higher API is associated with higher clinical event rates during follow-up in a multivariable model setting. Importantly, PISA-EROA and PISA-RV are not associated with clinical event rates in the multivariate model in this cohort. In secondary MR, it is difficult to identify the hemispherical shell for the PISA method because the orifice is often not circular but frequently hemiellipsoidal. API may have a superior measure compared with PISA methods in secondary MR on this matter. Among secondary MR, specific group (eg, proportionate MR) was non-effective subset by MitraClip, and will be managed conservatively. Hence, the crucial step to determine the need for interventions in secondary MR is the classification of MR, which may be frequently challenging in the presence of a discordant grading. We always use the multiparameters to quantify the degree of regurgitation except in the presence of mild or less MR (figure 1). Vena contracta width and PISA method are recommended and another parameter helps to assess the severity of MR when there is discordance between the quantified degree of MR and the clinical findings. The API method has a potential to assess the true grade of MR in the setting of more than mild MR.

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Figure 1

Decision tree for assessing severity of chronic mitral regurgitation by echocardiography. API, average pixel intensity; MR, mitral regurgitation; PISA, proximal isovelocity surface area; VC, vena contracta.

Our current understanding of assessing and treating patients with secondary MR is still limited. MitraClip has been shown to improve outcomes in the specific population. However, the two key steps that need to be accomplished to take a decision with regard to the indication of MitraClip in secondary MR are to confirm (1) actual MR grading and (2) presence of LV dysfunction. With the study of Kamoen et al, API now becomes another option in the assessment of MR grading that can be considered to identify severity. This method will provide the chance of reconsidering the indication of mitral intervention in secondary MR in the future.