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Latent class analysis to predict outcomes after surgery for primary mitral regurgitation: a scientific validation of common sense

Primary mitral regurgitation (MR) is one of the most common valvular heart lesions and a leading cause for cardiac surgery. Over the last several decades, the management of patients with primary MR has evolved. Moreover, the epidemiology of mitral valve disease has shifted with a marked decrease in the prevalence of rheumatic valve disease and an increase in myxomatous (degenerative) mitral valve disease, which is nowadays the most common aetiology of primary MR. Observational studies have described the negative sequelae of MR such as atrial fibrillation (AF), heart failure, left ventricular and atrial remodelling, left ventricle dysfunction and pulmonary hypertension, which has encouraged surgery to be performed earlier in the disease course. 2 Thus, surgery is recommended in asymptomatic patients with preserved ejection fraction (EF) in sinus rhythm at low surgical risk if the probability of repair is high and surgery is performed in experienced hands. However, such patients represent only a small proportion of those requiring an intervention, and risk stratification for most patients with primary MR remains an important question. Kwak et al have used an interesting methodology, namely latent class analysis (LCA), to identify phenotype groups with different outcomes after mitral valve surgery. LCA is a statistical method used to identify subsets of patients (latent groups or classes) within populations that share certain characteristics and experienced similar outcomes. To identify these latent groups, LCA uses study participants’ responses to various indicators (in the present study, mortality and surgical risks factors, respectively). In other words, LCA profiles the population to define distinct classes with similar indicators and responses. Although relying on different statistical principles, LCA shares significant similarities with cluster analysis, another statistical method designed to achieve a similar goal. The authors retrospectively collected data on 2321 patients with severe, isolated, pure primary MR who underwent native mitral valve surgery at three centres in Korea between 2006 and 2020. One centre’s population (N=1629) served as the derivation cohort and the other two centres as the validation cohort (N=692). The primary outcome was allcause mortality after the intervention (median followup 6 years). Fifteen indicators were included in the analysis, encompassing risk factors from the Society of Thoracic Surgeons Score, the Mitral Regurgitation International Database (MIDA) risk score, current guidelines and variables statistically associated with mortality in univariable analysis. The LCA identified five phenogroups: ► Group 1: young patients often paucisymptomatic with few comorbidities, degenerative MR, preserved EF who predominantly underwent isolated mitral valve repair. ► Groupe 2: young patients, all men, often symptomatic with a more advance disease stage than group 1 (ie, AF, evidence of left atrial and left ventricular remodelling and/or dysfunction) but with few comorbidities, degenerative MR and who benefited from a valve repair. ► Group 3: young symptomatic patients, mostly women, with rheumatic MR in AF who underwent a mitral valve replacement. ► Group 4: older patients with a modest burden of comorbidities and degenerative MR, early in the course of the disease who underwent a mitral valve repair. ► Group 5: older patients frequently with comorbidities, significant MR consequences, presenting with degenerative or rheumatic MR (onethird of patients) and in whom half underwent mitral valve replacement and 15% a coronary artery bypass surgery. The best outcome was observed in patients in group 1, followed by groups 2, 4, 3 and 5. Group 1 could be defined as low surgical risk, group 2 as relatively low risk, groups 3–4 as intermediate risk and group 5 as high surgical risk. Discrimination of the group phenotype was similar in the validation cohort, when the analysis was restricted to degenerative MR or when the full cohort was considered. Interestingly, in patients with degenerative MR, the phenogroup membership showed similar performance than the modified MIDA Score (tricuspid regurgitation velocity and not systolic pulmonary pressure was collected in the present study). What do we learn from this study and what are the clinical implications? First, this large cohort confirms the importance of wellrecognised prognostic factors in patients with MR being considered for surgery: age, comorbidities, MR consequences, MR aetiology (rheumatic vs degenerative disease), type of intervention (replacement vs repair) and combined versus isolated surgery. The present study adds to the current body of evidence showing that, to achieve the best outcomes, the mitral valve intervention should be performed early in the course of the disease. 7 These findings fully support current guidelines. Second, a repair should always be preferred when feasible even in the elderly. Multiple studies have shown superiority of repair compared with replacement. The present study further confirms the importance of centres’ and surgeons’ expertise and strongly supports referral of patients with MR to centres of excellence to achieve high repair rates and excellent outcomes. Third, degenerative MR is the main aetiology of primary MR in developed countries; however, rheumatic disease remains a concern and is frequently encountered (15% of the population), at least in Korea. In this young subset, the repair rate is low, and a mechanical valve replacement is often required. Fourth, the present study offers a relatively easy riskstratification algorithm. This classification is intuitive and not groundbreaking but has the merit of simplicity. In this regard, it should be emphasised that the main advantage of LCA is to detect unobserved heterogeneity in the population with specific patterns of responses to tested parameters. One may argue that the significant risk factors identified in this study were expected and have been previously described. However, LCA provides the rational and a formal demonstration of such class Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada