Abstract
Objectives: To optimise surgical treatment of mitral valve disease (MVD), a better understanding of gender-based differences is required. In this study, we analyse the gender-based differences among patients undergoing mitral valve surgery. Methods: Between January 2019 and December 2024, 809 consecutive patients were admitted to our centre for surgery for MVD. We analysed the patient characteristics, surgical details, postoperative and short-term outcomes of these patients. Results: Females (31.8%) undergoing mitral valve (MV) surgery were older (p < 0.001). Females had a higher rate of atrial fibrillation (p < 0.001), Rheumatoid arthritis (RA) (p = 0.002) and malignancy (p = 0.030). Furthermore, females were more often admitted to the intensive care unit (ICU) preoperatively (p = 0.037). Among these patients, 419 patients underwent isolated MV surgery. Furthermore, males underwent minimally invasive MV surgery more often (p = 0.004). Females had higher rates of combined MVD (p < 0.001) and combined MS (p < 0.001). Males had higher rates of severe mitral regurgitation (MR) (p = 0.041) and Left Atrium (LA) dilation (p = 0.004). Females exhibited higher rates of severe Tricuspid Regurgitation (TR) (p = 0.032) and pulmonary hypertension (p < 0.001). males had higher rates of posterior mitral leaflet (PML) prolapse (p < 0.001) and Flail leaflets (p < 0.001). Males underwent mitral valve repair (MVr) more often (p = 0.002). Early MACCE were reported in 5.1% of the patients. Freedom from major adverse cardiac and cerebrovascular events (MACCE) was comparable at 1 year and three years (p = 0.548). Prognosis and freedom from events were comparable between genders. Conclusions: Mitral valve disease presents differently across genders. There exist fundamental differences in the pathophysiological processes and presentation of mitral valve disease. Mitral valve surgery can be carried out with low mortality and morbidity rates irrespective of gender.
Keywords: mitral valve disease, gender
1. Introduction
Mitral regurgitation (MR) is the most common valvular heart disease worldwide and second most common in Europe, affecting about 1% to 2% of the world’s population [1,2]. In developed countries, mitral valve disease (MVD) accounts for about a quarter of valvular heart disease, with MR being more prevalent than mitral stenosis (MS). In Germany, the number of cases of rheumatic MVD has dropped drastically, whereas the number of cases of non-rheumatic MVD has more than doubled over the last 20 years (Figure 1) [3]. Females accounted for a higher number of cases of rheumatic MVD (Figure 2) [3]. In cases of MVD, gender specific differences are observed at the anatomic and pathophysiologic level [4].
Figure 1.
Mitral valve disease in Germany [3].
Figure 2.
Gender distribution of rheumatic and non-rheumatic mitral valve disease in Germany [3].
Generally, women suffer from MVD more frequently, whereas males develop aortic valve diseases or aortic stenosis associated with bicuspid aortic valves more often [1]. Females have been reported to have a less-elastic mitral annulus with a larger annular circumference, higher prevalence of rheumatic MVD and atrial secondary mitral regurgitation (ASMR) [4,5]. Furthermore, posterior mitral leaflet (PML) prolapse has been reported to be more common in male patients, whereas anterior mitral leaflet (AML) and bi-leaflet prolapse with myxomatous degeneration have been reported to be more common among female patients [1,4]. To optimise surgical treatment of MVD, a better understanding of gender-based differences is required. In this study, we analyse the gender-based differences among patients undergoing mitral valve (MV) surgery.
2. Methods
2.1. Ethics Statement
This study was approved by the ethics board of the Ludwig Maximilian University (No. 19-730 and 20-821) and the requirement to obtain patient consent was waived for this retrospective study. Postoperative treatment and data acquisition was performed as part of routine patient care. Data acquisition was based on institutional databases and then de-identified. All procedures described in this study were in accordance with the institutional ethics board and national data safety regulations.
2.2. Study Design
We reviewed patients undergoing MV surgery at our center between January 2019 and December 2024. Postoperative treatment and data acquisition was performed as part of routine patient care. All decisions were made in our interdisciplinary Heart-Team. Diagnosis and treatment was determined according to the current ESC/EACTS guidelines [6,7]. We analysed the patient characteristics, individual risk scores, surgical details, postoperative and short-term outcomes of these patients. To predict the postoperative mortality the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) as proposed by Nashef et al. [8] was calculated. A sub-group analysis was performed to analyse the outcomes following isolated mitral valve surgery. Primary outcomes were 30-day mortality and three-year survival. Major adverse cardiac and cerebrovascular events (MACCE) were defined by mortality of any cause, myocardial infarction and stroke. Early endocarditis was defined as endocarditis occurring within a year of surgery [9].
2.3. Data Collection, Statistical Analysis and Illustrations
Data were analysed using IBM SPSS version 29 (Statistical Package for the Social Sciences) (IBM-SPSS Inc., Armonk, NY, USA). Data was tested for normal distribution using the Kolmogorov–Smirnov test with Lillefors correction. Categorical variables were evaluated using the Chi-Squared and Fisher‘s exact method and continuous variables were evaluated using the Mann–Whitney-U test. We used single imputation to replace missing values. Missing continuous values were replaced with the mean value in normally distributed variables and with the median value in non-normally distributed variables. Missing categorical values were replaced with the mode [10]. Survival analysis was performed with Kaplan–Meier curve and log-rank test. All analyses were two tailed. The null hypothesis was rejected, and significant difference was assumed with p-values < 0.05. Data are presented as medians (25th–75th quartiles) or absolute values (percentages) unless otherwise specified. Illustrations were prepared using GraphPad Prism v 10 (GraphPad Software Inc, Boston, CA, USA).
3. Results
3.1. Patient Population
Between January 2019 and December 2024, 809 consecutive patients were admitted to our centre for MV surgery. Among these patients, 419 patients underwent isolated MV surgery. Demographic characteristics are presented in Table 1. Females undergoing MV surgery were older (p < 0.001). Females had higher rates of atrial fibrillation (p < 0.001), rheumatoid arthritis (RA) (p = 0.002) and malignancy (p = 0.030). Furthermore, females were more often admitted to the intensive care unit (ICU) preoperatively (p = 0.037). Males were treated more often with Single Antiplatelet Therapy (SAPT) (p = 0.027) and Vitamin K antagonists (VKA) were used more often in females (p = 0.005). There was no difference observed with regard to new oral anticoagulants (NOAC) (p = 0.282).
Table 1.
Baseline parameters.
| Mitral Valve Surgery | Isolated Mitral Valve Surgery | |||||
|---|---|---|---|---|---|---|
| Female (n = 257) |
Male (n = 552) |
p-Value | Female (n = 133) |
Male (n = 286) |
p-Value | |
| Patient characteristics | ||||||
| Age (years) | 69 (62–75) | 64 (56–72) | <0.001 | 67 (59–75) | 60 (55–69) | <0.001 |
| BMI (kg/m2) | 24 (20.8–28.0) | 26 (23.6–28.7) | <0.001 | 23.3 (20.2–26.7) | 25.5 (23.5–28.4) | <0.001 |
| EuroSCORE II (%) | 3.2 (1.7–6.5) | 2.4 (1.1–5.4) | <0.001 | 1.9 (1.2–3.5) | 1.2 (0.8–2.5) | <0.001 |
| Previous cardiac surgery (%) | 34 (13.2) | 83 (15.0) | 0.591 | 15 (11.4) | 40 (14.0) | 0.535 |
| Co-morbidities | ||||||
| Arterial Hypertension (%) | 168 (65.4) | 383 (69.4) | 0.258 | 73 (54.9) | 172 (60.1) | 0.338 |
| Insulin dependent Diabetes Mellitus (%) | 33 (12.8) | 66 (12.0) | 0.730 | 14 (10.5) | 27 (9.4) | 0.726 |
| Hyperlipoproteinemia (%) | 89 (34.6) | 186 (33.7) | 0.811 | 41 (30.8) | 74 (25.9) | 0.293 |
| Coronary artery Disease (%) | 84 (32.7) | 214 (38.8) | 0.101 | 25 (18.8) | 59 (20.6) | 0.696 |
| ICM (%) | 2 (0.8) | 9 (1.6) | 0.517 | 0 (0.0) | 0 (0.0) | - |
| DCM (%) | 4 (1.6) | 17 (3.1) | 0.243 | 1 (0.8) | 4 (1.4) | 1.000 |
| Peripheral artery disease (%) | 33 (12.8) | 57 (10.3) | 0.337 | 14 (10.5) | 20 (7.0) | 0.249 |
| Atrial Fibrillation (%) | 135 (52.5) | 219 (39.7) | <0.001 | 66 (49.6) | 104 (36.4) | 0.014 |
| Pacemaker (%) | 22 (8.6) | 33 (6.0) | 0.179 | 6 (4.5) | 15 (5.2) | 0.815 |
| PCI/PTCA (%) | 34 (13.2) | 59 (10.7) | 0.289 | 10 (7.5) | 18 (6.3) | 0.676 |
| Chronic Kidney Disease (%) | 40 (15.6) | 71 (12.9) | 0.324 | 14 (10.5) | 18 (6.3) | 0.165 |
| Dialysis (%) | 9 (3.5) | 21 (3.8) | 1.000 | 2 (1.5) | 77 (2.4) | 0.725 |
| Immunosuppressive Therapy (%) | 9 (3.5) | 15 (2.7) | 0.514 | 3 (2.3) | 5 (1.7) | 0.713 |
| Rheumatoid arthritis (%) | 17 (6.6) | 11 (2.0) | 0.002 | 5 (3.8) | 3 (1.0) | 0.116 |
| Endocarditis (%) | 33 (12.8) | 95 (17.2) | 0.121 | 19 (14.3) | 44 (15.4) | 0.883 |
| Malignancy (%) | 37 (14.4) | 53 (9.6) | 0.030 | 16 (12.0) | 25 (8.7) | 0.294 |
| Radiation (%) | 14 (5.4) | 17 (3.1) | 0.116 | 4 (3.0) | 6 (2.1) | 0.732 |
| IV Drug Abuse (%) | 2 (0.8) | 0 (0.0) | 0.101 | 1 (0.8) | 0 (0.0) | 0.318 |
| HIV Infection (%) | 1 (0.4) | 0 (0.0) | 0.318 | 1 (0.8) | 0 (0.0) | 0.317 |
| COPD (%) | 16 (6.2) | 27 (4.9) | 0.501 | 8 (6.0) | 15 (5.2) | 0.818 |
| Stroke (%) | 44 (17.1) | 67 (12.1) | 0.062 | 23 (17.3) | 33 (11.5) | 0.123 |
| Direct ICU admission (%) | 44 (17.1) | 67 (12.1) | 0.037 | 12 (9.0) | 23 (8.0) | 0.709 |
| Preoperative decompensation (%) | 39 (15.2) | 63 (11.4) | 0.140 | 16 (12.0) | 28 (9.8) | 0.497 |
| Anticoagulants | ||||||
| SAPT (%) | 59 (23.0) | 164 (29.8) | 0.027 | 20 (15.0) | 54 (18.9) | 0.409 |
| DAPT (%) | 7 (2.7) | 11 (2.0) | 0.609 | 2 (1.5) | 5 (1.7) | 1.000 |
| VKA (%) | 34 (13.2) | 38 (6.9) | 0.005 | 13 (9.8) | 16 (5.6) | 0.147 |
| NOAC | 82 (31.9) | 155 (28.1) | 0.282 | 42 (31.6) | 66 (23.2) | 0.045 |
3.2. Mitral Valve Pathology and Echocardiographic Data
Preoperative echocardiographic data are depicted in Table 2. Females had higher rates of combined MVD (p < 0.001) and combined MS (p < 0.001). Males had higher rates of severe MR (p = 0.041) and left atrium (LA) dilation (p = 0.004). Females exhibited higher rates of severe tricuspid regurgitation (TR) (p = 0.032) and pulmonary hypertension (p < 0.001). With regard to the MV, males had higher rates of PML prolapse (p < 0.001) and Flail leaflets (p < 0.001). We observed no differences with regard to AML prolapse and Barlow disease.
Table 2.
Echocardiographic data on admission.
| Mitral Valve Surgery | Isolated Mitral Valve Surgery | |||||
|---|---|---|---|---|---|---|
| Female (n = 257) |
Male (n = 552) |
p-Value | Female (n = 133) |
Male (n = 286) |
p-Value | |
| Aortic Stenosis | ||||||
| Mild to moderate (%) | 21 (8.2) | 38 (6.9) | 0.562 | 2 (1.5) | 4 (1.4) | 1.000 |
| Severe (%) | 15 (5.8) | 27 (4.9) | 0.611 | 0 (0.0) | 1 (0.3) | 1.000 |
| Aortic Regurgitation | ||||||
| Mild to moderate (%) | 27 (10.5) | 52 (9.4) | 0.613 | 4 (3.0) | 2 (0.7) | 0.084 |
| Severe (%) | 5 (1.9) | 23 (4.2) | 0.147 | 0 (0.0) | 0 (0.0) | - |
| Combined mitral valve disease | 55 (21.4) | 52 (9.4) | <0.001 | 21(15.8) | 16 (5.6) | 0.001 |
| Mitral Stenosis | 57 (22.2) | 57 (10.3) | <0.001 | 22 (16.5) | 18 (6.3) | 0.002 |
| Mild to moderate (%) | 34 (13.2) | 27 (4.9) | <0.001 | 11 (8.3) | 7 (2.4) | 0.009 |
| Severe | 15 (5.8) | 12 (2.2) | 0.011 | 7 (5.3) | 6 (2.1) | 0.126 |
| Mitral Regurgitation | 255 (99.2) | 545 (98.7) | 0.727 | 132 (99.2) | 283 (99.0) | 1.000 |
| Mild to moderate (%) | 105 (40.9) | 205 (37.1) | 0.314 | 56 (42.1) | 91 (31.8) | 0.026 |
| Severe (%) | 123 (47.9) | 307 (55.6) | 0.041 | 64 (48.1) | 183 (64.0) | 0.003 |
| Tricuspid Regurgitation | ||||||
| Mild to moderate (%) | 68 (26.5) | 90 (16.3) | <0.001 | 17 (12.8) | 27 (9.4) | 0.308 |
| Severe (%) | 19 (7.4) | 22 (4.0) | 0.032 | 1 (0.8) | 1 (0.3) | 0.535 |
| LVEF | ||||||
| >55% (%) | 174 (67.7) | 386 (69.9) | 0.567 | 106 (79.7) | 238 (83.2) | (0.796) |
| 30–55% (%) | 75 (29.2) | 144 (26.1) | 0.395 | 27 (20.3) | 48 (16.8) | 0.412 |
| <30% (%) | 0 (0.0) | 4 (0.7) | 0.313 | 0 (0.0) | 0 (0.0) | - |
| Pulmonary Hypertension (%) | 127 (49.4) | 186 (33.7) | <0.001 | 56 (42.1) | 69 (24.1) | <0.001 |
| LV dilation | 38 (27.1) | 119 (41.5) | 0.004 | 14 (22.6) | 51 (37.0) | 0.031 |
| LA dilation | 136 (87.2) | 271 (82.1) | 0.188 | 62 (84.9) | 131 (80.4) | 0.468 |
| Posterior Mitral Leaflet prolapse | 94 (36.6) | 281 (50.9) | <0.001 | 68 (51.1) | 191 (66.8) | 0.002 |
| P1 Segment | 52 (20.2) | 131 (23.7) | 0.280 | 36 (27.1) | 81 (28.3) | 0.816 |
| P2 Segment | 87 (33.9) | 258 (46.7) | <0.001 | 64 (48.1) | 179 (62.6) | 0.006 |
| P3 Segment | 56 (21.8) | 156 (28.3) | 0.030 | 38 (28.6) | 102 (35.7) | 0.182 |
| Anterior Mitral Leaflet prolapse | 43 (16.7) | 104 (18.8) | 0.494 | 20 (15.0) | 51 (17.8) | 0.576 |
| A1 Segment (%) | 36 (14.0) | 66 (12.0) | 0.427 | 14 (10.5) | 31 (10.8) | 1.000 |
| A2 Segment (%) | 41 (16.0) | 81 (14.7) | 0.673 | 18 (13.5) | 38 (13.3) | 1.000 |
| A3 Segment (%) | 37 (14.4) | 83 (15.0) | 0.915 | 15 (11.3) | 38 (13.3) | 0.637 |
| Flail (%) | 69 (26.8) | 217 (39.3) | <0.001 | 45 (33.8) | 139 (48.6) | 0.006 |
| Barlow Disease (%) | 43 (16.7) | 74 (13.5) | 0.238 | 32 (24.1) | 46 (16.1) | 0.037 |
3.3. Surgical Data
Details of surgery are presented in Table 3. The median cardiopulmonary bypass time (p < 0.001) and cross clamping time (p < 0.001) was higher among males. Furthermore, males underwent minimally invasive MV surgery more often (p = 0.004), and the valve was repaired rather than replaced more frequently (p = 0.002) in males than in females We observed no differences with regard to the individual repair techniques. Intra-operative repair failure was reported in 36 patients (4.4%) and was comparable between the groups (p = 0.720). Females underwent concomitant tricuspid valve repair more often (p < 0.001), whereas males underwent concomitant coronary artery bypass grafting (CABG) procedures more frequently (p < 0.001).
Table 3.
Details of surgery.
| Mitral Valve Surgery | Isolated Mitral Valve Surgery | |||||
|---|---|---|---|---|---|---|
| Female (n = 257) |
Male (n = 552) |
p-Value | Female (n = 133) |
Male (n = 286) |
p-Value | |
| Duration of CPB (%) | 137 (107–177) | 159 (126–196) | <0.001 | 118 (94–158) | 140 (111–172) | <0.001 |
| Duration of Aortic X-clamping (%) | 91 (71–114) | 103 (80–128) | <0.001 | 77 (63–95) | 89 (73–110) | <0.001 |
| Minimally invasive surgery (%) | 28 (10.9) | 105 (19.0) | 0.004 | 26 (19.5) | 101 (35.3) | <0.001 |
| Isolated Mitral valve surgery | 133 (51.8) | 286 (51.8) | 1.000 | - | - | - |
| Mitral valve repair (%) | 107 (41.6) | 294 (53.3) | 0.002 | 67 (50.4) | 192 (67.1) | 0.001 |
| Ring annuloplasty (%) | 107 (100.0) | 290 (98.6) | 0.577 | 63 (47.4) | 200 (69.9) | <0.001 |
| Alfieri stich (%) | 0 (0.0) | 2 (0.7) | 1.000 | 0 (0.0) | 2 (0.7) | 1.000 |
| Triangular resection (%) | 1 (0.9) | 6 (2.0) | 0.680 | 0 (0.0) | 8 (2.8) | 0.046 |
| Quadrangular resection (%) | 2 (1.9) | 8 (2.7) | 1.000 | 1 (0.8) | 8 (2.8) | 0.283 |
| Neochordae (%) | 87 (81.3) | 240 (81.6) | 1.000 | 65 (48.9) | 191 (66.8) | <0.001 |
| Cleft closure (%) | 42 (39.3) | 95 (32.3) | 0.234 | 29 (21.8) | 73 (25.5) | 0.464 |
| Mitral valve replacement | ||||||
| Biological prosthesis (%) | 106 (70.7) | 167 (64.7) | 0.274 | 41 (30.8) | 52 (18.2) | 0.005 |
| Mechanical prosthesis (%) | 44 (29.3) | 91 (35.2) | 0.228 | 24 (18.0) | 42 (14.7) | 0.390 |
| MV repair failure (%) | 12 (8.0) | 24 (9.3) | 0.720 | 6 (4.5) | 12 (4.2) | 1.000 |
| Aortic valve surgery | ||||||
| Biological prosthesis (%) | 49 (19.1) | 85 (15.4) | 0.223 | 0 (0.0) | 0 (0.0) | - |
| Mechanical prosthesis (%) | 5 (1.9) | 33 (6.0) | 0.012 | 0 (0.0) | 0 (0.0) | - |
| Repair (%) | 1 (0.4) | 4 (0.7) | 1.000 | 0 (0.0) | 0 (0.0) | - |
| Tricuspid valve surgery | ||||||
| Biological prosthesis (%) | 6 (2.3) | 7 (1.3) | 0.367 | 0 (0.0) | 0 (0.0) | - |
| Mechanical prosthesis (%) | 1 (0.4) | 1 (0.2) | 0.535 | 0 (0.0) | 0 (0.0) | - |
| Repair (%) | 61 (23.7) | 66 (12.0) | <0.001 | 0 (0.0) | 0 (0.0) | - |
| LV-aneurysm resection (%) | 1 (0.4) | 6 (1.1) | 0.441 | 0 (0.0) | 0 (0.0) | - |
| VSD closure (%) | 1 (0.4) | 2 (0.4) | 1.000 | 0 (0.0) | 0 (0.0) | - |
| PFO closure (%) | 23 (8.9) | 67 (12.1) | 0.189 | 11 (8.3) | 34 (11.9) | 0.311 |
| LAA closure (%) | 125 (48.6) | 210 (38.0) | 0.005 | 58 (43.6) | 96 (33.6) | 0.031 |
| Ablation (%) | 66 (25.7) | 130 (23.6) | 0.538 | 35 (26.3) | 70 (24.5) | 0.717 |
| CABG (%) | 21 (8.2) | 104 (18.8) | <0.001 | 0 (0.0) | 0 (0.0) | - |
| Aortic surgery (%) | 6 (2.3) | 26 (4.7) | 0.123 | 0 (0.0) | 0 (0.0) | - |
| Patch plasty (%) | 29 (11.3) | 37 (6.8) | 0.038 | 8 (6.0) | 11 (3.9) | 0.324 |
3.4. Morbidities and Outcomes
Postoperative morbidities and outcomes are listed in Table 4. We observed no differences with regard to postoperative adverse cerebrovascular events, myocardial infarction, new onset atrial fibrillation between the groups.
Table 4.
Morbidities and outcomes.
| Mitral Valve Surgery | Isolated Mitral Valve Surgery | |||||
|---|---|---|---|---|---|---|
| Female (n = 257) |
Male (n = 552) |
p-Value | Female (n = 133) |
Male (n = 286) |
p-Value | |
| Morbidities | ||||||
| Adverse cerebrovascular events (%) | 11 (4.3) | 20 (3.6) | 0.695 | 7 (5.3) | 5 (1.7) | 0.049 |
| Delirium | 39 (15.2) | 62 (11.2) | 0.137 | 22 (16.5) | 20 (7.0) | 0.005 |
| Surgical site reexploration (%) | 43 (16.7) | 110 (20.0) | 0.290 | 13 (9.8) | 43 (15.0) | 0.166 |
| New myocardial infarction (%) | 1 (0.4) | 9 (1.6) | 0.183 | 0 (0.0) | 2 (0.7) | 1.000 |
| RCX obstruction | 1 (0.4) | 7 (1.3) | 0.447 | 1 (0.8) | 3 (1.0) | 1.000 |
| Renal Replacement therapy (%) | 30 (11.7) | 68 (12.3) | 0.908 | 6 (4.5) | 19 (6.6) | 0.508 |
| Pneumonia (%) | 97 (37.7) | 203 (36.8) | 0.815 | 48 (36.1) | 88 (30.8) | 0.313 |
| Tracheostoma (%) | 7 (2.7) | 27 (4.9) | 0.189 | 0 (0.0) | 5 (1.7) | 0.183 |
| ECLS support (%) | 17 (6.6) | 39 (7.1) | 0.883 | 5 (3.8) | 10 (3.5) | 1.000 |
| Duration of ECLS support (%) | 5 (3–8) | 5 (3–7) | 0.633 | 6 (3–9) | 6 (5–7) | 0.839 |
| Surgical site infection (%) | 14 (5.4) | 20 (3.6) | 0.259 | 5 (3.8) | 9 (3.1) | 0.774 |
| Pacemaker implantation (%) | 15 (5.8) | 41 (7.4) | 0.459 | 2 (1.5) | 8 (2.8) | 0.514 |
| New atrial fibrillation (%) | 58 (22.6) | 122 (22.1) | 0.928 | 28 (21.1) | 53 (18.5) | 0.595 |
| AV Block III | 20 (7.8) | 59 (10.7) | 0.206 | 6 (4.5) | 12 (4.2) | 1.000 |
| Outcomes | ||||||
| Mitral Regurgitation at discharge | ||||||
| Trace (%) | 76 (29.6) | 175 (31.7) | 0.568 | 45 (33.8) | 97 (33.9) | 1.000 |
| Mild to moderate (%) | 1 (0.4) | 5 (0.9) | 0.671 | 0 (0.0) | 4 (1.4) | 0.312 |
| Severe (%) | 0 (0.0) | 1 (0.2) | 1.000 | 0 (0.0) | 0 (0.0) | - |
| Mitral valve PGmax | 10 (6–15) | 9 (6–15) | 0.090 | 7.3 (5.0–12.0) | 12.0 (12.0–12.0) | 0.008 |
| Mitral valve PGmean | 4 (3–5) | 3 (2–5) | 0.002 | 3.7 (3.0–4.5) | 3.0 (3.0–6.0) | 0.027 |
| Tricuspid Regurgitation at discharge | ||||||
| Trace (%) | 130 (50.6) | 301 (54.5) | 0.325 | 76 (57.1) | 170 (59.4) | 0.671 |
| Mild to moderate (%) | 22 (8.6) | 16 (2.9) | <0.001 | 9 (6.8) | 10 (3.5) | 0.139 |
| Severe (%) | 1 (0.4) | 0 (0.0) | 0.318 | 0 (0.0) | 0 (0.0) | - |
| Hospital stay (days) | 16 (13–24) | 16 (12–24) | 0.350 | 15 (12–21) | 14 (11–19) | 0.046 |
| ICU stay (days) | 5 (4–7) | 5 (3–7) | 0.465 | 5 (3–6) | 4 (3–6) | 0.067 |
| Duration of ventilation (hours) | 16 (12–24) | 17 (12–24) | 0.196 | 14 (12–24) | 15 (12–24) | 0.487 |
| In-hospital Mortality (%) | 15 (5.9) | 26 (4.7) | 0.494 | 5 (3.8) | 5 (1.7) | 0.299 |
At discharge, we found no differences regarding the degree of mitral regurgitation between the groups. However, we did observe a higher mean gradient over the mitral valve among females (p = 0.002). Furthermore, females had higher rates of mild to moderate tricuspid valve regurgitation (p < 0.001). We observed no differences with regard to hospital stay and ICU stay. The total in-hospital mortality of the cohort was 5.1%, and 2.4% among those undergoing isolated MV surgery and was comparable between the groups.
On follow-up, a total of 1.5% (n = 12) of patients suffered from adverse cerebrovascular events and 0.1% (n = 1) suffered from myocardial infarctions (Table 5). Early MACCE were reported in 5.1% of the patients. Freedom from MACCE was comparable at 1 year (females 91% vs. males 90%) and three years (females 80% vs. males 71%) (p = 0.548). We did not observe any differences between the groups. Survival at 1 year (females 91% vs. males 84%) and 3 years (females 89% vs. males 85%) was comparable between the groups (p = 0.384) (Figure 3).
Table 5.
Outcomes of Follow-up.
| Total (n = 809) |
Female (n = 257) |
Male (n = 552) |
p-Value | |
|---|---|---|---|---|
| Stroke (%) | 12 (1.5) | 4 (1.6) | 8 (1.4) | 1.000 |
| New myocardial infarction (%) | 1 (0.1) | 1 (0.4) | 0 (0.0) | 0.318 |
| Infective endocarditis (%) | 17 (2.1) | 3 (1.2) | 14 (2.5) | 0.294 |
| Early infective endocarditis (%) | 9 (1.1) | 3 (1.1) | 6 (1.1) | 0.206 |
| Early MACCE (%) | 41 (5.1) | 13 (5.1) | 28 (5.0) | 1.000 |
Figure 3.
Gender adjusted survival and freedom from MACCE following mitral valve surgery.
3.5. Isolated Mitral Valve Surgery
In our cohort, 419 (51.8%) patients underwent isolated MV surgery. Females undergoing isolated MV surgery were older than males (p < 0.001). Females had a higher rate of atrial fibrillation (p = 0.014) and had higher rates of NOAC use (p = 0.045). Females had higher rates of combined MV disease (p = 0.001) and mitral stenosis (p = 0.002), whereas males had a higher rate of severe mitral regurgitation (p = 0.003) and presented with a PML prolapse more often (p = 0.002). Barlow disease was more common in females (p = 0.037). Males underwent MVr more frequently than females (p = 0.001), whereas females underwent MVR with biological prostheses more frequently (p = 0.005). Postoperatively, females had a higher rates of adverse cerebrovascular events (p = 0.049) and delirium (p = 0.005). The in-hospital mortality was 3.8% among females and 1.7% among males (p = 0.299).
4. Discussion
4.1. Mitral Valve Disease and the Female Patient
MV disease presents differently in males and females. This is due to anatomical and pathophysiological factors [4]. In addition to the above-mentioned differences, male patients may present with more posterior mitral leaflet calcification whereas female patients may present with more annular calcification [1,4]. Females have also been reported to present with generalized myxomatous degeneration of the MV [4]. This is reflected in our cohort too. We found a higher rate of Barlow disease among females undergoing isolated MV surgery.
The 2021 ESC guidelines define mitral regurgitation as severe based on an integrative approach that includes a combination of qualitative, semiquantitative, quantitative, and morphological criteria, such as left ventricular and atrial dilation [2]. As female patients generally have smaller cardiac dimensions than male patients, size-related criteria may contribute to a delayed diagnosis of severe mitral regurgitation in women [4]. This delay may lead to more advanced stages of MVD in females at the time of referral for surgery and could explain the higher prevalence of atrial fibrillation, pulmonary hypertension, and severe tricuspid regurgitation observed in female patients in our cohort. Furthermore, we found that a higher number of females were admitted directly to the ICU. Even among patients undergoing transcatheter MV interventions, women tended to be significantly older [11]. Early referral of females with MVD may lead to improved outcomes.
We found higher rates of TR and pulmonary hypertension among females. TR is associated with poorer outcomes following mitral valve surgery. Atrial fibrillation, rheumatic etiology, dilated atria, LV dysfunction, and preoperative TR have been reported as significant risk factors for TR following MV surgery [12].
In our cohort, females had a higher prevalence of both RA and MS. Typical lesions in RA-associated valvular heart disease include valve nodules and leaflet fibrosis, which may extend to the annulus and subvalvular apparatus [13]. However, MS is more commonly associated with RHD than with RA [14]. Among patients suffering from MVD associated with RA long-term survival after MVr is equivalent to those suffering from RA without MVD. However, patients with RA and MVD have a lower survival as compared to those undergoing surgery without RA [15]. Given that RHD is known to be more prevalent in females, this raises the question of whether RHD may be underdiagnosed in European cohorts with MS [16]. In general, MS and mitral annular calcification have been reported to be more prevalent in females than in men, possibly influencing negative outcomes accordingly [17,18,19].
Another important aspect of MVD is infective endocarditis (IE). In cases of IE, males have been reported to be older and to suffer from aortic valve endocarditis more often, whereas females tend to be younger and suffer from mitral valve endocarditis more frequently [20,21]. Among patients undergoing surgery for IE, female patients have been reported to present with a higher rate of comorbidities, higher surgical risk profile, and have more frequently experienced postoperative morbidities than male patients [22]. In our cohort, we found no differences regarding the incidence of IE between males and females, even among those undergoing isolated MV surgery. Furthermore, upon follow-up, we found the incidence of IE to be as low as 2.1%, with 1.1% of the patients suffering from early endocarditis, and no differences between the groups.
4.2. Treatment and Outcomes of Mitral Valve Disease
MVr is the surgical intervention of choice in patients with mitral regurgitation since it is associated with better survival compared with MVR [2]. As durable surgical repair has been reported to be highest for isolated posterior mitral leaflet prolapse, females may have poorer outcomes due to suboptimal surgical repair due to more complex valvular pathologies [4]. In our cohort too, males underwent MVr more frequently, even in cases of isolated MV surgery. Several studies report poorer long term outcomes for females and higher durability of repair among males [23,24]. Andari et al. [25] report that females undergoing MV surgery were found to have increased rates of short-term mortality. In our cohort, we did not observe and differences in the short and mid-term mortality among patients undergoing MV surgery. Furthermore, women have been reported to present with post-operative heart failure more frequently. This may be related to later referral and more advanced disease at the time of surgery compared to men [2]. We observed higher rates of adverse cerebrovascular events and postoperative delirium among females undergoing isolated MV surgery.
Seeburger et al. [26] identified differences in surgical strategies for the correction of MR between genders. They report that females underwent MVR more than twice as often than males. Although several factors such as comorbidities and presenting MV pathology may govern such decisions, the rate of MVr needs to be improved in women. Even though MVR can be performed with comparable outcomes in males and females irrespective of age, the outcomes of MVR are poorer compared to those of MVr [24,27]. Since women present with mitral stenosis or combined MV pathologies more often, repair of stenotic MVs especially due to rheumatic pathology, is not easy in many cases and the surgeon may be forced to replace the valve if repair is considered impossible or non-durable [28]. Furthermore, women tend to be referred later for MV surgery [21,29]. This may be due to several factors, such as lack of index echocardiographic parameters, underestimated severity of MVD and a more fulminant course than in males. Moreover, it has been reported that less than 25% of patients with heart valve disease (specifically mitral and tricuspid regurgitation) who meet indications for referral are referred for invasive treatment [30].
4.3. Limitations
This is a retrospective single-centre study with the inherent limitation of such an analysis. Patients undiagnosed or treated conservatively were out of the scope of this study. The small number of patients is associated with a low power of statistical analyses. Due to the small sample size a multivariable analysis was not performed. A longer study duration is required, to account for changing trends such as MICS MV surgery.
5. Conclusions
Mitral valve disease presents differently across genders. There exist fundamental differences in the pathophysiological processes and presentation of mitral valve disease. This should be taken into consideration while diagnosing these patients especially while planning surgical interventions. Finally, mitral valve surgery can be carried out with low mortality and morbidity rates irrespective of gender.
Abbreviations
| AML | anterior mitral leaflet |
| ASMR | atrial secondary mitral regurgitation |
| BMI | body mass index |
| CABG | coronary artery bypass grafting |
| COPD | chronic obstructive pulmonary disease |
| CPB | cardiopulmonary bypass |
| DAPT | Dual anti-platelet treatment |
| DCM | dilative cardiomyopathy |
| ESC | European society of Cardiology |
| EuroSCORE II | European System for Cardiac Operative Risk Evaluation II |
| FFP | fresh frozen plasma |
| HIV | human immunodeficiency viruses |
| ICM | ischemic cardiomyopathy |
| ICU | intensive care unit |
| IE | infective endocarditis |
| IV | intravenous |
| LA | left atrium |
| LAA | left atrial appendage |
| LV | left ventricle |
| LVEF | left ventricular ejection fraction |
| MACCE | major adverse cardiac and cerebrovascular events |
| MR | mitral regurgitation |
| MS | mitral stenosis |
| MV | mitral valve |
| MVD | mitral valve disease |
| MVr | mitral valve repair |
| MVR | mitral valve replacement |
| NOAC | new oral anticoagulants |
| PCI/PTCA | percutaneous coronary intervention/percutaneous transluminal coronary angioplasty |
| PFO | patent foramen ovale |
| PG | pressure gradient |
| PML | posterior mitral leaflet |
| PRBC | packed red blood cells |
| RA | rheumatoid arthritis |
| RCX | ramus circumflexus |
| RHD | rheumatic heart disease |
| SAPT | single anti-platelet treatment |
| sPAP | systolic pulmonary artery pressure |
| TR | tricuspid regurgitation |
| VKA | vitamin K antagonist |
| VSD | ventricular septum defect |
Author Contributions
Conceptualization, S.S.; Methodology, S.S. and D.J.; Validation, G.J., S.P. and C.H.; Formal analysis, S.S. and D.J.; Investigation, K.M.H. and A.A.; Data curation, S.M.; Writing—original draft, S.S. and D.J.; Writing—review & editing, S.S. and M.S.; Supervision, C.H. All authors have read and agreed to the published version of the manuscript.
Institutional Review Board Statement
This study was conducted according to the guidelines of the Declaration of Helsinki and was approved by the ethics board of the Ludwig Maximilian University (Approval no: 23-0828 and Approval Date: 26 February 2024).
Informed Consent Statement
Not applicable, as this study was retrospective.
Data Availability Statement
The data underlying this study cannot be shared publicly in accordance with national data safety guidelines, to protect the privacy of individuals that included in the study. The data will be shared on reasonable request to the corresponding author.
Conflicts of Interest
The authors of this manuscript declare that they have no conflicts of interest, had full control of the design and methods of the study, data analysis and production of the written report, and that no funding supported this study.
Funding Statement
No funding has been provided regarding this article.
Footnotes
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.
References
- 1.Desjardin J.T., Chikwe J., Hahn R.T., Hung J.W., Delling F.N. Sex Differences and Similarities in Valvular Heart Disease. Circ. Res. 2022;130:455–473. doi: 10.1161/CIRCRESAHA.121.319914. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Vahanian A., Beyersdorf F., Praz F., Milojevic M., Baldus S., Bauersachs J., Capodanno D., Conradi L., De Bonis M., De Paulis R., et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease: Developed by the Task Force for the management of valvular heart disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Rev. Esp. Cardiol. 2022;75:524. doi: 10.1016/j.rec.2022.05.006. [DOI] [PubMed] [Google Scholar]
- 3.German Federal Statistical Office n.d. [(accessed on 20 January 2025)]. Available online: https://www.destatis.de.
- 4.Ocher R., May M., Labin J., Shah J., Horwich T., Watson K.E., Yang E.H., Press M.A. Mitral Regurgitation in Female Patients: Sex Differences and Disparities. J. Soc. Cardiovasc. Angiogr. Interv. 2023;2:101032. doi: 10.1016/j.jscai.2023.101032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Avierinos J.-F., Inamo J., Grigioni F., Gersh B., Shub C., Enriquez-Sarano M. Sex Differences in the Morphology and Outcomes of Mitral Valve Prolapse: A Cohort study. Ann. Intern. Med. 2008;149:787–795. doi: 10.7326/0003-4819-149-11-200812020-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Baumgartner H., Falk V., Bax J.J., De Bonis M., Hamm C., Holm P.J., Iung B., Lancellotti P., Lansac E., Muñoz D.R., et al. 2017 ESC/EACTS Guidelines for the management of valvular heart disease The Task Force for the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European. Eur. Heart J. 2017;38:2739–2791. doi: 10.1093/eurheartj/ehx391. [DOI] [PubMed] [Google Scholar]
- 7.Vahanian A., Beyersdorf F., Praz F., Milojevic M., Baldus S., Bauersachs J., Capodanno D., Conradi L., De Bonis M., De Paulis R., et al. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. EuroIntervention. 2022;17:e1126-96. doi: 10.4244/EIJ-E-21-00009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Nashef S.A.M., Roques F., Sharples L.D., Nilsson J., Smith C., Goldstone A.R., Lockowandt U. Euroscore II. Eur. J. Cardio-Thorac. Surg. 2012;41:734–745. doi: 10.1093/ejcts/ezs043. [DOI] [PubMed] [Google Scholar]
- 9.Delgado V., Ajmone Marsan N., De Waha S., Bonaros N., Brida M., Burri H., Caselli S., Doenst T., Ederhy S., Erba P.A., et al. 2023 ESC Guidelines for the management of endocarditis. Eur. Heart J. 2023;44:3948–4042. doi: 10.1093/eurheartj/ehad193. [DOI] [PubMed] [Google Scholar]
- 10.Papageorgiou G., Grant S.W., Takkenberg J.J.M., Mokhles M.M. Statistical primer: How to deal with missing data in scientific research? Interact. Cardiovasc. Thorac. Surg. 2018;27:153–158. doi: 10.1093/icvts/ivy102. [DOI] [PubMed] [Google Scholar]
- 11.Werner N., Puls M., Baldus S., Lubos E., Bekeredjian R., Sievert H., Schofer J., Kuck K.-H., Möllmann H., Hehrlein C., et al. Gender-related differences in patients undergoing transcatheter mitral valve interventions in clinical practice: 1-year results from the German TRAMI registry. Catheter. Cardiovasc. Interv. 2020;95:819–829. doi: 10.1002/ccd.28372. [DOI] [PubMed] [Google Scholar]
- 12.Matsuyama K., Matsumoto M., Sugita T., Nishizawa J., Tokuda Y., Matsuo T. Predictors of residual tricuspid regurgitation after mitral valve surgery. Ann. Thorac. Surg. 2003;75:1826–1828. doi: 10.1016/S0003-4975(03)00028-6. [DOI] [PubMed] [Google Scholar]
- 13.Roldan C.A., DeLong C., Qualls C.R., Crawford M.H. Characterization of Valvular Heart Disease in Rheumatoid Arthritis by Transesophageal Echocardiography and Clinical Correlates. Am. J. Cardiol. 2007;100:496–502. doi: 10.1016/j.amjcard.2007.03.048. [DOI] [PubMed] [Google Scholar]
- 14.Iung B., Baron G., Butchart E.G., Delahaye F., Gohlke-Bärwolf C., Levang O.W., Tornos P., Vanoverschelde J.-L., Vermeer F., Boersma E., et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on valvular heart disease. Eur. Heart J. 2003;24:1231–1243. doi: 10.1016/S0195-668X(03)00201-X. [DOI] [PubMed] [Google Scholar]
- 15.Stulak J.M., Suri R.M., Matteson E.L., Dearani J.A., Connolly H.M., Schaff H.V. Mitral valve repair is durable in patients with rheumatoid arthritis. Ann. Thorac. Surg. 2012;94:510–515. doi: 10.1016/j.athoracsur.2012.03.028. [DOI] [PubMed] [Google Scholar]
- 16.Mutagaywa R.K., Wind A.M., Kamuhabwa A., Cramer M.J., Chillo P., Chamuleau S. Rheumatic heart disease anno 2020: Impacts of gender and migration on epidemiology and management. Eur. J. Clin. Investig. 2020;50:e13374. doi: 10.1111/eci.13374. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Afifi A., Hosny H., Yacoub M. Rheumatic aortic valve disease-when and who to repair? Ann. Cardiothorac. Surg. 2019;8:383–389. doi: 10.21037/acs.2019.05.01. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Movahed M.R., Ahmadi-Kashani M., Kasravi B., Saito Y. Increased Prevalence of Mitral Stenosis in Women. J. Am. Soc. Echocardiogr. 2006;19:911–913. doi: 10.1016/j.echo.2006.01.017. [DOI] [PubMed] [Google Scholar]
- 19.Churchill T.W., Yucel E., Bernard S., Namasivayam M., Nagata Y., Lau E.S., Deferm S., He W., Danik J.S., Sanborn D.Y., et al. Sex Differences in Extensive Mitral Annular Calcification With Associated Mitral Valve Dysfunction. Am. J. Cardiol. 2023;193:83–90. doi: 10.1016/j.amjcard.2023.02.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Slouha E., Al-Geizi H., Albalat B.R., Burle V.S., Clunes L.A., Kollias T.F. Sex Differences in Infective Endocarditis: A Systematic Review. Cureus. 2023;15:e49815. doi: 10.7759/cureus.49815. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Deng M.X., Barodi B., Elbatarny M., Yau T.M. Considerations & challenges of mitral valve repair in females: Diagnosis, pathology, and intervention. Curr. Opin. Cardiol. 2024;39:86–91. doi: 10.1097/HCO.0000000000001107. [DOI] [PubMed] [Google Scholar]
- 22.Ackermann P., Marin-Cuartas M., Weber C., De La Cuesta M., Lichtenberg A., Petrov A., Hagl C., Aubin H., Matschke K., Diab M., et al. Sex-related differences in patients with infective endocarditis requiring cardiac surgery: Insights from the CAMPAIGN Study Group. Eur. J. Cardio-Thorac. Surg. 2024;66:ezae292. doi: 10.1093/ejcts/ezae292. [DOI] [PubMed] [Google Scholar]
- 23.Liu K., Ye Q., Zhao Y., Zhao C., Song L., Wang J. Sex Differences in the Outcomes of Degenerative Mitral Valve Repair. Ann. Thorac. Cardiovasc. Surg. 2023;29:192–199. doi: 10.5761/atcs.oa.22-00210. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Vassileva C.M., McNeely C., Mishkel G., Boley T., Markwell S., Hazelrigg S. Gender differences in long-term survival of medicare beneficiaries undergoing mitral valve operations. Ann. Thorac. Surg. 2013;96:1367–1373. doi: 10.1016/j.athoracsur.2013.04.055. [DOI] [PubMed] [Google Scholar]
- 25.EL-Andari R., Bozso S.J., Fialka N.M., Kang J.J.H., Nagendran J. Does sex impact outcomes after mitral valve surgery? A systematic review and meta-analysis. Scand. J. Surg. 2022;111:99–109. doi: 10.1177/14574969221124468. [DOI] [PubMed] [Google Scholar]
- 26.Seeburger J., Eifert S., Pfannmüller B., Garbade J., Vollroth M., Misfeld M., Borger M., Mohr F.W. Gender differences in mitral valve surgery. Thorac. Cardiovasc. Surg. 2013;61:42–46. doi: 10.1055/s-0032-1331583. [DOI] [PubMed] [Google Scholar]
- 27.Mokhles M.M., Siregar S., Versteegh M.I.M., Noyez L., van Putte B., Vonk A.B.A., Roos-Hesselink J.W., Bogers A.J.J.C., Takkenberg J.J.M. Male-female differences and survival in patients undergoing isolated mitral valve surgery: A nationwide cohort study in the Netherlands. Eur. J. Cardio Thorac. Surg. 2016;50:482–487. doi: 10.1093/ejcts/ezw151. [DOI] [PubMed] [Google Scholar]
- 28.Alkady H., Saber A., Abouramadan S., Elnaggar A., Nasr S., Mahmoud E. Mitral valve replacement in mitral stenosis; the problem of small left ventricle. J. Cardiothorac. Surg. 2020;15:67. doi: 10.1186/s13019-020-01108-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Kislitsina O.N., Zareba K.M., Bonow R.O., Andrei A.C., Kruse J., Puthumana J., Akhter N., Malaisrie S.C., McCarthy P.M., Rigolin V.H., et al. Is mitral valve disease treated differently in men and women? Eur. J. Prev. Cardiol. 2019;26:1433–1443. doi: 10.1177/2047487319833307. [DOI] [PubMed] [Google Scholar]
- 30.Doenst T., Enriquez Sarano M., Kirov H., Caldonazo T., Chikwe J., Dreyfus J., Zacharias J. Lifetime management of heart valve disease—Treat it early and treat it right, first time. Lancet. 2025;6736:9–10. doi: 10.1016/S0140-6736(25)00989-4. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data underlying this study cannot be shared publicly in accordance with national data safety guidelines, to protect the privacy of individuals that included in the study. The data will be shared on reasonable request to the corresponding author.