Mitral Regurgitation: Should There Be Female-Specific Intervention Thresholds?

Mitral regurgitation: sex, a critical variable still underestimated

Mitral regurgitation (MR) illustrates a persistent paradox in interventional cardiology: although it affects nearly 2% of the adult population, its clinical approach remains largely undifferentiated. This literature review synthesizes current data regarding sex-related disparities in the presentation, evaluation, and outcomes of mitral valve interventions, revealing a care pathway that is often more complex and delayed for female patients.

The findings presented by the authors are striking: women are diagnosed at a more advanced age, present with more severe symptoms, and carry a higher burden of comorbidities compared to men. Yet, they experience longer delays before intervention, are less frequently referred to Heart Teams, and benefit less often from valve repair techniques (plasty) in favor of prosthetic replacement. The objective of this review is to document these inequalities to question the validity of current standards of care.

Compiled data suggest that conventional intervention thresholds, based on raw ultrasound measurements not indexed to body surface area, systematically penalize women. The central hypothesis is that this lack of anatomical precision induces a detrimental delay in management. This synthesis calls for a transition toward sex-specific thresholds to optimize surgical timing and clinical outcomes in MI.

Methodology of the synthesis

This article provides a review of the scientific literature aimed at synthesizing sex-related disparities in the presentation, evaluation, and clinical outcomes of patients treated for mitral regurgitation (MR). The authors analyze evidence accumulated since the late 2000s to identify gaps between men and women in surgical and percutaneous care pathways.

The synthesis is based on the analysis of several large-scale data sources:

• A Spanish national cohort study involving more than 300,000 patients admitted with a diagnosis of MI.
• A post-hoc analysis of the CSTN SIMR (Comparing the Effectiveness of Repairing Versus Replacing the Heart’s Mitral Valve) clinical trial focused on severe ischemic MI.
• The examination of international registries including data on minimally invasive mitral valve surgery (MIMVS) and transcatheter interventions.

The methodological evaluation segments the results according to the pathophysiology of the pathology: primary (organic) MR and secondary (functional, including ischemic, ventricular, and atrial etiologies) MR. Analysis criteria include the demographic profile (age, comorbidities via the Charlson index), symptomatic severity, referral times to multidisciplinary teams, and the adequacy of current intervention thresholds (LVESD and LVEF) specifically for the female population.

Clinical profiles and epidemiological disparities

This literature review highlights marked differences in the presentation of mitral regurgitation (MR) according to sex. The authors report, based on a large Spanish cohort (Zamorano et al., n > 300,000), that women are diagnosed at an older age and with a heavier burden of comorbidities.

Indicators (Zamorano et al.)	Women	Men	Significance (p)
Average age at diagnosis	80 years	75 years	< 0.001
Charlson Comorbidity Index	6.00	5.00	< 0.001
Prevalence Primary MI (n)	112 650	70 355	< 0.001
Prevalence Secondary MR (n)	47 036	77 242	< 0.001

The synthesis also highlights a phenotypic distinction within secondary MR (SMR): women represent a higher proportion of atrial SMR cases (4,358 vs. 3,036; p < 0.001), while men are the majority in ventricular forms.

Symptomatology and diagnostic evaluation

Functionally, female patients present with more severe symptoms. Post-hoc analysis of the CSTN SIMR trial shows that, for an equivalent NYHA class, women display significantly impaired quality of life scores (Minnesota Living With Heart Failure) compared to men (53.1 vs 45.0; p = 0.03).

Despite this clinical severity, access to interventions remains unequal:

• Multidisciplinary evaluation: According to Waldron et al., women with Class I indications for primary MR have a significantly lower probability of undergoing evaluation by the "Heart Team" (OR 0.27 [95% CI: 0.15–0.47]; p < 0.001).
• Surgical pathway: Female patients face longer waiting times and are less frequently referred for minimally invasive surgery (MIMVS), as indicated by the work of Dębski et al., despite long-term post-operative results comparable to those of men.

A marked asymmetry in the care pathway

The data reported by this review highlight a systematic disparity: women access mitral surgery at a more advanced age, with increased symptomatic severity and a higher burden of comorbidities. Clinically, this delay in management is concerning. Female patients present longer intervals before intervention and less frequently benefit from valve repair (plasty) compared to replacement, despite long-term results comparable to men when they access minimally invasive techniques.

The study highlights a critical point for diagnosis: echocardiographic measurements of mitral regurgitation (MR) severity and left ventricular cavity dimensions differ significantly by sex. However, current guidelines do not take these specificities into account. This lack of indexing could explain why women are less frequently referred for Heart Team evaluation, even when they meet Class I intervention criteria (severe symptomatic or asymptomatic MR with ventricular dysfunction/dilation).

Research limits and imperatives

The weak point identified by the authors lies in the heterogeneity of the data. While the less favorable post-operative prognosis in women is documented for primary MR, the evidence is more fragile and dated regarding secondary MR. Furthermore, results concerning transcatheter interventions (MTEER) remain too disparate to allow for a rigorous comparison with conventional surgery. The absence of sex-specific intervention thresholds constitutes a major barrier to precision medicine.

This review highlights a marked gender disparity: women, although representing the majority in primary mitral regurgitation (PMR) and a minority in the secondary form (SMR), are referred later for surgery and benefit less often from valve repair than men. They nevertheless present more severe symptoms and a heavier comorbidity profile at the time of intervention, while current imaging criteria do not consider female morphological specificities.", "practitioner_takeaways": [ Adjust your imaging alert thresholds: as quantitative measurements and left ventricular cavity sizes differ by sex, current intervention thresholds may delay the management of female patients.", "relevance": "Clinical practice / Evaluation" }, Accelerate the care pathway: as women undergo longer intervention delays, early referral to the Heart Team is crucial to improve repair versus replacement rates.", "relevance": "Therapeutic orientation" }, Differentiate phenotype by gender: keep in mind that women constitute the majority of PMR cases, but are more likely to present secondary mitral regurgitation of atrial rather than ventricular origin.", "relevance": "Differential diagnosis" ], "formatted_article": "

Summary of disparities in management

This systematic review highlights that women, although representing the majority in primary mitral regurgitation, are referred later for surgery and benefit less frequently from valve repair than men. The compiled data indicate that they present with more severe symptomatology and a higher burden of comorbidities, while current imaging criteria do not account for the female morphological specificities of the left ventricle.

In concrete terms, for the practitioner:

• Adjust your alert thresholds: Systolic ventricular diameters should be interpreted with caution, as non-indexed standard criteria often underestimate the true severity of MR in women.
• Accelerate the care pathway: When faced with a female patient presenting with MRR, do not delay the Heart Team's opinion; intervention times are structurally longer and surgery rates are lower for this population.
• Target the surgical strategy: Anticipate increased complexity due to more advanced age, while prioritizing mitral repair to mitigate the excessive use of prosthetic replacement historically observed in female patients.

Mitral regurgitation (MR) remains the most common valvular heart disease, affecting nearly 2% of the adult population. While epidemiological differences between sexes are well known, a recent review highlights persistent and concerning disparities in the care pathway for women, from initial assessment to post-operative outcomes.

---

Information intended for healthcare professionals. This content may contain errors or truncated summaries. We recommend always verifying with the original source article. Delynov disclaims all responsibility regarding the use of this information. This document is not intended for patients or the general public.