Abstract
Background
Gender‐ and sex‐based disparities in mitral valve disease exist; however the factors associated with these differences are unknown. Identifying these differences is essential in devising mitigating strategies. We evaluated gender and sex differences among patients with severe primary mitral regurgitation (MR) across treatment phases.
Methods and Results
We conducted a retrospective cohort study of patients with new diagnoses of severe primary MR between 2016 and 2020. We compared multidisciplinary evaluation incidence and 2‐year survival between men and women. We analyzed a subgroup meeting class 1 indications for intervention, which includes severe symptomatic MR or severe asymptomatic MR with ejection fraction <60% or left ventricular end‐systolic diameter >40 mm. Logistic regression models identified predictors associated with the likelihood of multidisciplinary evaluation. Among 330 patients meeting class 1 indications, women were older (79 versus 76 years, P=0.01) and had higher Society of Thoracic Surgeons risk scores for mitral valve repair than men (2.5% versus 1.4%, P=0.003). Women were less likely to undergo multidisciplinary evaluation (57% versus 84%, P<0.001) and intervention (47% versus 69%, P<0.001) than men. Median days to intervention for women and men were 77 and 43, respectively. Women had a higher 2‐year mortality rate than men (31% versus 21%, P=0.035). On a multivariable model, female sex and older age were associated with lower odds of undergoing multidisciplinary evaluation (odds ratio, 0.26; P<0.001; odds ratio, 0.95; P<0.001, respectively).
Conclusions
Women with severe primary MR with class 1 indication for intervention were less likely to undergo multidisciplinary evaluation and intervention and had a longer interval to intervention than men. Survival was comparable after accounting for age and comorbidity differences.
Keywords: mitral regurgitation, mitral valve, mitral valve repair, sex differences
Subject Categories: Clinical Studies, Valvular Heart Disease, Cardiovascular Surgery, Disparities, Mortality/Survival
Nonstandard Abbreviations and Acronyms
- MR
mitral regurgitation
- MV
mitral valve
- STS
Society of Thoracic Surgeons
- TEER
transcatheter edge‐to‐edge repair
Clinical Perspective.
What Is New?
This study evaluated the gender and sex differences in patient characteristics, rates of multidisciplinary evaluation and intervention, and survival among patients with severe primary mitral regurgitation.
What Are the Clinical Implications?
Women with class 1 indication for intervention were older, were less likely to receive multidisciplinary evaluation, were less likely to undergo mitral valve intervention, and had a longer interval to intervention among those treated and worse unadjusted survival than men.
Survival after the diagnosis of mitral regurgitation was comparable after matching for age and comorbidity differences.
Gender and sex differences in the patient presentation, treatment timeliness, and outcomes are prevalent in cardiovascular disease. 1 , 2 , 3 Gender‐ and sex‐based disparities are particularly important in degenerative mitral valve (MV) disease, as timely mechanical correction of severe primary mitral regurgitation (MR) has the potential to restore quality of life and life expectancy. 4 , 5 , 6 Untreated MR could lead to pulmonary hypertension, ventricular dysfunction, atrial fibrillation, tricuspid regurgitation, and heart failure. 7 Because women have been shown to have underdiagnosis, undertreatment, and delay in care, 8 it is critical to characterize these disparities and their potential impact on outcomes in women with MV disease to prevent adverse sequelae and restore normal life expectancy. 9 , 10 , 11 , 12
The factors associated with these differences remain unknown. Additionally, our understanding is limited on the differences that may occur at earlier triaging stages, including referral to multidisciplinary evaluation after diagnosis and selection of intervention among the broader cohort of those with degenerative disease. Identifying and understanding the treatment phases where this disparity occurs is essential in devising strategies to mitigate these differences.
Using a health care network–wide echocardiogram database, we aimed to compare the patient characteristics and early and midterm outcomes of patients with newly detected severe primary MR between men and women across treatment phases from diagnosis to intervention. We also sought to identify patient factors associated with the likelihood of undergoing multidisciplinary evaluation for MV disease.
Methods
The data that support the findings of this study are available from the corresponding author upon reasonable request. This study was conducted after the approval of our institutional ethics committee (2000028791). Because this was a retrospective study, the requirement to obtain informed consent was waived.
Patient Population
We conducted a retrospective cohort study at Yale–New Haven Health, a large health care network in the United States, encompassing 10 inpatient sites in academic and community settings and 440 outpatient clinics at satellite locations throughout Connecticut and Rhode Island. The system‐wide electronic medical record database was queried to identify patients aged ≥18 years who received a complete (as opposed to focused examination) transthoracic echocardiogram for any indication between January 1, 2016, and December 31, 2020, either during inpatient or outpatient encounters. These included echocardiograms obtained from 32 sites.
We restricted the cohort to severe MR of primary pathogenesis using the following criteria: mitral leaflet being described using the words “prolapsed,” “prolapse,” “degenerative,” “flail,” or “myxomatous” and included only patients for whom this was the first identification of severe MR among all echocardiograms performed during the study period. Patients with mitral stenosis of any severity or endocarditis of any valve were excluded. Patients with prior valve operations were also excluded. We focused on severe primary MR to homogenize the patient group to those with higher likelihood of needing MV intervention or operation.
Variable Definitions
The exposure variable was multidisciplinary evaluation, which was defined as documentation of evaluation by both a cardiology service and cardiac surgery during the course of workup toward a potential intervention. 6 Patients who underwent evaluation by a multidisciplinary team were categorized as “evaluated,” whereas those who did not were categorized as “unevaluated.” The term multidisciplinary evaluation is used instead of heart team, as the system did not have a formalized heart team consisting of teams specifically dedicated to the evaluation and treatment of mitral structural disease throughout the entire study period.
Demographics, admission details, follow‐up care, and echocardiogram measurements were extracted from medical records. Gender identity was not surveyed separately. However, given the intricacies of sex and gender in cardiovascular health, we interpreted differences between the 2 groups as those associated with both sex and gender. Admission details included the reason for admission and documented heart failure symptoms. Echocardiogram measurements included the presence and severity of mitral annular calcification, left ventricular end‐systolic diameter, left ventricular ejection fraction (LVEF), and left atrial volume. The Society of Thoracic Surgeons (STS) predicted 30‐day risk of death for MV repair and replacement were calculated for each patient. 13 Patient mortality rate was adjudicated by the combination of Connecticut Vital Statistics Database linkage, which captures all Connecticut State residents' deaths occurring in and out of the state, supplemented with individual patient chart review.
Outcome Measures
Primary endpoints during follow‐up were multidisciplinary evaluation and 2‐year all‐cause mortality. Additional end points included meeting class 1 indications for intervention. We restricted the follow‐up to 2 years since the index echocardiogram to ensure that all patients had the potential for a complete follow‐up.
Statistical Analysis
Bivariate analyses compared patient characteristics, operative details, postoperative outcomes, and STS predicted risk of death between men and women. Wilcoxon rank‐sum tests were used for continuous variables, and the median and interquartile range were reported. 2 tests were used for categorical variables, which were summarized by percentages. The Fisher exact test was used if cell counts were 5. Unadjusted survival was estimated using a Kaplan–Meier plot.
To estimate the association between gender and sex and the pattern of referral and management of primary MR, we also analyzed a subgroup meeting class 1 indications for intervention in primary MR, which included either severe symptomatic MR or severe asymptomatic MR with LVEF <60% or left ventricular end‐systolic diameter >40 mm6. Additionally, to analyze the impact of patient characteristics and comorbidity on outcomes, 1:1 propensity score matching between men and women among those meeting class 1 indication for intervention was performed using a logistic regression model with age; race; heart failure symptoms; inpatient setting; and history of myocardial infarction, dementia, renal failure, hypertension, cerebral vascular disease, diabetes, prior coronary artery bypass surgery, peripheral vascular disease, and atrial fibrillation or flutter as the covariates. We used the nearest‐neighbor method and a caliper size of 0.06. A total of 216 patients were matched between the 2 groups. The quality of matching was evaluated using propensity score density and a Love plot. A logistic regression model was fitted to identify variables associated with the likelihood of being evaluated by a multidisciplinary team, which we defined as a documentation of evaluation by both a cardiology service and cardiac surgery. Statistical significance was defined as P<0.05. Analyses were performed in R version 4.2.2 (R Foundation for Statistical Computing, Vienna, Austria).
Results
Patient Characteristics
There were 70 510 unique patients who underwent an echocardiogram during the study period, of which 391 had severe primary MR, a prevalence consistent with a prior population‐based study. 14 The analysis was conducted on 391 patients with severe primary MR (Figure 1). Among the 391 patients with severe primary MR, the median age was 77 (interquartile range [IQR], 65–85) years, and 180 (46%) were women. The echocardiograms were predominantly obtained in an inpatient setting (N=248 [63%]). Women tended to be older (median age, 79 [IQR, 67–88] years versus 76 [IQR, 64–83] years), were less frequently referred to multidisciplinary evaluation (N=102/180 [57%] versus N=170/211 [81%]), and underwent fewer interventions than men: 142 (67%) men underwent surgery (N=117) or transcatheter edge‐to‐edge repair (TEER) (N=25), whereas 86 (48%) women underwent surgery (N=75) or TEER (N=11). The median STS predicted 30‐day mortality rate for MV repair was higher for women (2.3% [IQR, 1.0%–5.0%] versus 1.3% [IQR, 0.5%–3.8%]) than men (Table 1).
Figure 1. Flowchart of inclusion criteria.
This flowchart displays the inclusion criteria for our study and the distribution of patients who did and did not meet class I indication for intervention. MR indicates mitral regurgitation.
Table 1.
Patient Characteristics, Risk Scores, and Outcomes
| Characteristic | Total (N=391) | Men (N=211) | Women (N=180) | P value |
|---|---|---|---|---|
| Age, y | 77 (65–85) | 76 (64–83) | 79 (67–88) | 0.004* |
| Race, n (%) | ||||
| White | 328 (84) | 173 (82) | 155 (86) | 0.5 |
| Black | 32 (8.2) | 19 (9.0) | 13 (7.2) | |
| Other† | 31 (7.9) | 19 (9.0) | 12 (6.7) | |
| Inpatient echocardiogram, n (%) | 248 (63) | 130 (62) | 118 (66) | 0.4 |
| Hypertension, n (%) | 245 (63) | 136 (64) | 109 (61) | 0.4 |
| Diabetes, n (%) | 53 (14) | 34 (16) | 19 (11) | 0.11 |
| Prior CABG, n (%) | 10 (2.6) | 9 (4.3) | 1 (0.6) | 0.024* |
| Heart failure, n (%) | 85 (22) | 45 (21) | 40 (22) | 0.8 |
| PVD, n (%) | 56 (14) | 38 (18) | 18 (10) | 0.024* |
| Myocardial infarction, n (%) | 29 (7.4) | 16 (7.6) | 13 (7.2) | 0.9 |
| Atrial fibrillation/flutter, n (%) | 116 (30) | 64 (30) | 52 (29) | 0.8 |
| Cerebral vascular disease, n (%) | 52 (13) | 26 (12) | 26 (14) | 0.5 |
| Renal failure, n (%) | 42 (11) | 28 (13) | 14 (7.8) | 0.08* |
| Liver disease, n (%) | 5 (1.3) | 2 (0.9) | 3 (1.7) | 0.7 |
| Rheumatoid arthritis, n (%) | 8 (2.0) | 2 (0.9) | 6 (2.2) | 0.2 |
| Dementia, n (%) | 10 (2.6) | 5 (2.4) | 5 (2.8) | >0.9 |
| Depression, n (%) | 32 (8.2) | 14 (6.6) | 18 (10) | 0.2 |
| Cancer, n (%) | 88 (23) | 45 (21) | 43 (24) | 0.5 |
| Heart failure symptoms, n (%) | 291 (74) | 164 (78) | 127 (71) | 0.11 |
| MAC, n (%) | ||||
| Moderate | 43 (11) | 17 (8.1) | 26 (14) | <0.001* |
| Severe | 16 (4.1) | 7 (3.3) | 9 (5.0) | |
| LVESD (mm) | 33 (28–39) | 35 (31–41) | 30 (26–36) | <0.001* |
| Left atrial volume | 102 (76–128) | 112 (88–141) | 89 (72–116) | <0.001* |
| LVEF, % | 61 (55–66) | 60 (54–64) | 62 (55–67) | 0.064 |
| STS predicted risk of death: replacement, % | 5 (2–10) | 4 (2–9) | 6 (3–13) | <0.001* |
| STS predicted risk of death for MV repair, % | 1.5 (0.7–4.5) | 1.3 (0.5–3.8) | 2.3 (1.0–5.5) | <0.001* |
| Multidisciplinary evaluation, n (%) | 272 (70) | 170 (81) | 102 (57) | <0.001* |
| Surgery, n (%) | 192 (49) | 117 (55) | 75 (42) | 0.007* |
| TEER, n (%) | 36 (9.2) | 25 (12) | 11 (6.1) | 0.051 |
| MV replacement, n (%) | 32 (12) | 20 (12) | 12 (12) | 0.8 |
| Follow‐up duration, d | 730 (729–730) | 730 (729–730) | 729 (729–730) | 0.1 |
| Days to intervention | 51 (5–146) | 43 (4–134) | 76 (6–146) | 0.2 |
| Class 1 indication, n (%) | 292 (75) | 165 (79) | 127 (71) | 0.069 |
This table summarizes the characteristics, risk scores, and outcomes of the 391 patients with new diagnoses of severe primary MR between 2016 and 2020.
CABG indicates coronary artery bypass graft; LVESD, left ventricular end‐systolic diameter; LVEF, left ventricular ejection fraction; MAC, mitral annular calcification; MV, mitral valve; PVD, peripheral vascular disease; STS, Society of Thoracic Surgeons; and TEER, transcatheter edge‐to‐edge repair.
P values were statistically significant.
Other indicates race not otherwise captured.
Overall Survival
Patients who did not experience an event had a median of 730 (IQR, 729–730) follow‐up days, indicating a near‐complete follow‐up for this 2‐year study. Women experienced higher all‐cause death than men at 90 days, 1 year, and 2 years (16% versus 10%, 23% versus 14%, and 29% versus 20%, respectively; P value by log‐rank test <0.001; Figure S1).
Class 1 Indication for Intervention
Among patients meeting class 1 indication for intervention, 183 were men and 143 were women (89% versus 79%, P=0.006, respectively). Among the 330 patients meeting class 1 indications (median age, 77 [IQR 65–85] years; 44% women), women tended to be older (median age, 79 [IQR, 68–87] years versus 76 [IQR, 64–83] years; P=0.01) and had a higher median STS predicted risk of 30‐day death for MV repair (2.5% [IQR, 1.0%–5.9%] versus 1.4% [IQR, 0.6%–4.1%]; P=0.002) than men. The LVEF was comparable between men and women, at 58% (IQR, 52%–63%) and 59% (IQR, 54%–64%; P=0.7). Women experienced lower rates of referral to multidisciplinary evaluation (N=82/143 [57%] versus N=157/187 [84%], P<0.001) and were less likely to undergo intervention than men: 130 (69%) men underwent surgery (N=105) or TEER (N=25), whereas 67 (47%) women underwent surgery (N=57) or TEER (N=10) (P=0.003, P=0.062, respectively). The median time to intervention following the index echocardiogram was observed to be longer for women at 77 days, compared with 43 days for men, although it was not statistically significant (P=0.2; Table 2).
Table 2.
Patient Characteristics, Risk Scores, and Outcomes Meeting Class 1 Indication for Intervention
| Characteristic | Total (N=330) | Men (N=187) | Women (N=143) | P value |
|---|---|---|---|---|
| Age, y | 77 (65–85) | 76 (64–83) | 79 (68–87) | 0.01* |
| Race, n (%) | ||||
| White | 277 (84) | 155 (83) | 122 (85) | 0.8 |
| Black | 24 (7.3) | 15 (8.0) | 9 (6.3) | |
| Other† | 29 (8.8) | 17 (9.1) | 12 (8.4) | |
| Inpatient echocardiogram, n (%) | 212 (64) | 116 (62) | 96 (67) | 0.3 |
| Hypertension, n (%) | 209 (63) | 120 (64) | 89 (62) | 0.7 |
| Diabetes, n (%) | 51 (15) | 33 (18) | 18 (13) | 0.2 |
| Prior CABG, n (%) | 10 (3.0) | 9 (4.8) | 1 (0.7) | 0.047* |
| Heart failure, n (%) | 82 (25) | 45 (24) | 37 (26) | 0.7 |
| PVD, n (%) | 54 (16) | 38 (20) | 16 (11) | 0.026* |
| Myocardial infarction, n (%) | 25 (7.6) | 14 (7.5) | 11 (7.7) | >0.9 |
| Atrial fibrillation/flutter, n (%) | 106 (32) | 59 (32) | 47 (33) | 0.8 |
| Cerebral vascular disease, n (%) | 41 (12) | 20 (11) | 21 (15) | 0.3 |
| Renal failure, n (%) | 40 (12) | 27 (15) | 13 (9.1) | 0.14 |
| Liver disease, n (%) | 5 (1.5) | 2 (1.1) | 3 (2.1) | 0.7 |
| Rheumatoid arthritis, n (%) | 7 (2.1) | 2 (1.1) | 5 (3.5) | 0.2 |
| Dementia, n (%) | 6 (1.8) | 4 (2.1) | 2 (1.4) | 0.7 |
| Depression, n (%) | 26 (7.9) | 12 (6.4) | 14 (9.8) | 0.3 |
| Cancer, n (%) | 72 (22) | 41 (22) | 31 (22) | 0.9 |
| Heart failure symptoms, n (%) | 291 (88) | 164 (88) | 127 (89) | 0.8 |
| MAC, n (%) | ||||
| Moderate | 34 (10) | 16 (8.6) | 18 (13) | <0.001* |
| Severe | 14 (4.2) | 6 (3.2) | 8 (5.6) | |
| LVESD (mm) | 33 (29–39) | 35 (31–41) | 30 (26–37) | <0.001* |
| Left atrial volume | 100 (76–131) | 112 (87–148) | 88 (69–118) | <0.001* |
| LVEF (%) | 58 (52–64) | 58 (52–63) | 59 (54–64) | 0.7 |
| STS predicted risk of death for MV replacement, % | 5 (2–11) | 4 (2–9) | 7 (3–14) | 0.002* |
| STS predicted risk of death for MV repair, % | 1.7 (0.7–5.0) | 1.4 (0.6–4.1) | 2.5 (1.0–5.9) | 0.002* |
| Multidisciplinary evaluation, n (%) | 239 (72) | 157 (84) | 82 (57) | <0.001* |
| Surgery, n (%) | 162 (49) | 105 (55) | 57 (40) | 0.003* |
| TEER, n (%) | 35 (11) | 25 (13) | 10 (7.0) | 0.062 |
| MV replacement, n (%) | 29 (12) | 19 (13) | 10 (12) | 0.8 |
| Follow‐up duration, d | 730 (729–730) | 730 (729–730) | 729 (729–730) | 0.073 |
| Days to intervention | 47 (5–142) | 43 (4–130) | 77 (6–147) | 0.2 |
This table summarizes the characteristics, risk scores, and outcomes of the 330 patients who met class 1 indications for intervention with new diagnoses of severe primary MR between 2016 to 2020.
CABG indicates coronary artery bypass graft; LVESD, left ventricular end‐systolic diameter; LVEF, left ventricular ejection fraction; MAC, mitral annular calcification; MV, mitral valve; PVD, peripheral vascular disease; STS, Society of Thoracic Surgeons; and TEER, transcatheter edge‐to‐edge repair.
P values were statistically significant.
Other indicates race not otherwise captured.
Among patients meeting class 1 indication for intervention, women experienced a higher all‐cause mortality rate than men at 90 days, 1 year, and 2 years (17% versus 11%, 25% versus 14%, and 31% versus 21%, respectively; P value by log‐rank test = 0.02; Figure 2).
Figure 2. Kaplan–Meier curve of patients meeting class 1 indication.
This Kaplan–Meier curve shows the 2‐year survival between men (blue) and women (red) patients meeting class 1 indication for intervention.
Propensity Score Matching
There were 216 patients matched among those meeting class 1 indication for intervention: 108 men and 108 women. The propensity score variance ratio was 1.01, and the standard mean difference was 0.016, indicating an acceptable match (Figure S2). After propensity score matching, the baseline patient characteristics, risk scores, and outcomes were similar between men and women (Table S1). Among the matched patients, the Kaplan–Meier curve demonstrated that matching for patient baseline characteristics and comorbidities reduced the survival disparity between women and men at 30 days (6.5% versus 6.5%) and 2 years (27% versus 19%; P‐value by log‐rank test = 0.3; Figure 3).
Figure 3. Kaplan–Meier curve after propensity score matching among class 1 indication.
This Kaplan–Meier curve shows the 2‐year survival of men (blue) and women (red) patients after propensity score matching.
Multivariable Logistic Regression
On multivariable logistic regression model, female sex (odds ratio, 0.26 [95% CI, 0.15–0.45]), increased STS predicted risk of death (odds ratio, 0.94 [95% CI, 0.89–0.99] per 1% increase), and older age (odds ratio, 0.95 [95% CI, 0.93–0.98] per 1 year increase) were associated with lower odds of undergoing multidisciplinary evaluation among patients meeting class 1 indication (Table 3).
Table 3.
Characteristics Associated With Odds of Patient Receiving Multidisciplinary Evaluation Among Patients Meeting Class 1 Indications
| Characteristic | Odds ratio | 95% CI | P value |
|---|---|---|---|
| Female | 0.27 | 0.15–0.47 | <0.001* |
| STS predicted risk of death mitral repair | 0.94 | 0.89–0.99 | 0.026* |
| Age (per 1 y increase) | 0.95 | 0.93–0.98 | <0.001* |
| Ejection fraction (per 1% increase) | 1.03 | 1.00–1.05 | 0.06 |
This table displays the results from multivariable logistic regression of characteristics associated with evaluation by a multidisciplinary heart team.
STS indicates Society of Thoracic Surgeons.
P values were statistically significant.
Discussion
Our study evaluated the gender and sex differences between men and women presenting with severe primary MR across treatment phases since the time of first diagnosis within a large health care network in the northeastern United States. We observed gender‐ and sex‐based differences at multiple stages of patient care among unmatched patients with severe primary MR meeting class 1 indication for intervention: (1) Women were older at the time of initial diagnosis of severe MR, (2) were less likely to undergo multidisciplinary evaluation and be intervened on, and (3) had a longer interval until intervention or surgery among those who did undergo mechanical correction; furthermore, (4) women had worse unadjusted survival than men 2 years after the index echocardiogram.
This study adds to the literature, as there is a lack of data investigating the factors associated with these gender‐ and sex‐based disparities and the time point at which these differences originate. The optimization of patient selection, procedural planning, and management approaches for individual patients necessitates early detection of MR followed by referral to a multidisciplinary team, which is a class 1 recommendation by both US and European cardiovascular societies for patients with severe primary MR. 6 , 15 Additionally, MV surgery is the gold standard of treatment, with delayed surgery being associated with worse long‐term outcomes. 15 , 16 , 17
Age at Diagnosis
Women were older and had a higher median STS predicted risk of 30‐day death score, among both the overall cohort and patients meeting class 1 indication for intervention. These findings mirror trends seen throughout cardiovascular disease, spanning coronary disease, thoracic and abdominal aneurysms, and cerebral and peripheral vascular disease. 2 , 16 , 17 , 18 , 19 One potential factor associated with this disparity is that the class 1 guidelines of LVEF and left ventricular end‐systolic diameter cutoffs for asymptomatic patients do not consider that female patients generally have smaller cardiac dimensions than male patients or that healthy female patients may have a higher LVEF than healthy male patients. 11 , 20 , 21 Given that the data that formed the basis for operative indications are based on predominantly male populations, it is possible that female patients may in fact have underrecognized prognostically significant MR at an earlier stage than male patients do. Such differences may argue for establishing sex‐specific thresholds for intervention.
Multidisciplinary Evaluation and Intervention
Women were also less likely to be referred to multidisciplinary evaluation and subsequently less likely to undergo intervention, including both surgery and TEER. This trend persisted among the patients meeting class 1 indication for intervention, suggesting that this disparity was not associated with a difference in the strength of indication for intervention.
Interval to Intervention
The time to intervention for evaluated patients was prompt, although women had a longer time to intervention than men, at 72 days compared with 46 days among patients meeting class 1 indication. Although the difference in this interval was not statistically significant, previous studies have suggested that social or economic factors may influence differences in health care–seeking behavior between men and women. 22 Regardless, reducing this difference in time to intervention is a key step in mitigating disparity, allowing for early intervention for patients with severe primary MR.
Two‐Year Mortality Rate Among Patients Meeting Class 1 Indication
Among patients with class 1 indication for intervention, women had worse short and long‐term survival outcomes than men. The older age at presentation partly explains worse survival. After propensity score matching for baseline characteristics, age, and comorbidities, the survival outcome disparity disappeared, suggesting that a factor associated with the gender‐based disparity in survival outcomes may be the worst preoperative comorbidity profile and increased age of women compared with men. Studies on the timing of symptom onset and frequency of echocardiographic surveillance between genders are needed to understand whether there is a delay in diagnosis among women with significant MR. While different in scope from our study, studies that focus exclusively on transcatheter interventions, both edge‐to‐edge repair and replacement, have shown equivalent or improved outcomes for women compared with men. 23 , 24 , 25 The reasons underlying this difference between surgical and transcatheter outcomes between men and women are unclear and require further investigation.
Our analysis revealed that women had the lowest odds of undergoing multidisciplinary evaluation, which is a modifiable factor and consistent with prior literature demonstrating gender‐based differences in the management of cardiovascular disease. 1 , 3 Undergoing multidisciplinary evaluation standardizes and streamlines timely detection, referral, and the navigation of an increasing number of treatment options. Understanding the magnitude of this missed referral to multidisciplinary evaluation is a key step toward reducing the undertreatment of these women who may qualify for MV surgery or TEER. One potential bias‐free approach to mitigate this disparity in referral rates is the implementation of an automated internal trigger sent to the multidisciplinary team when the transthoracic echocardiogram is read to include severe MR.
Limitations
This study has several limitations, including the single‐center nature of the study that limits generalizability. However, the health system is large and includes a broad range of case settings throughout the state of Connecticut, spanning both inpatient and outpatient echocardiograms. The observational nature of this study prevents determining causal relationships. While analyses were performed to account for potential confounders, there may be residual confounding. Gender identity was not surveyed separately from sex, and so gender data are limited to cisgender‐identifying individuals.
Conclusions
Compared with men, women with severe primary MR with class 1 indication for intervention were older, were less likely to receive multidisciplinary evaluation, were less likely to undergo MV intervention, and had a longer interval to intervention among those treated and worse unadjusted survival. Survival after the diagnosis of MR was comparable after matching for age and comorbidity differences.
Sources of Funding
This study was funded by the Surgeon‐Scientist Training Program at Yale School of Medicine.
Disclosures
Dr Krane is a physician proctor and a member of the medical advisory board for the Jaspanese Organization for Medical Device Development, a physician proctor for Peter Duschek, a medical consultant for Evotec and Moderna, and has received speakers' honoraria from Medtronic and Terumo. Dr Geirsson receives a consulting fee from Medtronic and Edwards Lifesciences. The remaining authors have no disclosures to report.
Supporting information
Data S1
Table S1
Figures S1–S2
This manuscript was sent to Pamela N. Peterson, MD, Deputy Editor, for review by expert referees, editorial decision, and final disposition.
Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.123.033635
For Sources of Funding and Disclosures, see page 8.
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Associated Data
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Supplementary Materials
Data S1
Table S1
Figures S1–S2