Abstract
Introduction
This study aimed to elucidate gender differences in cardiac function among patients undergoing aortic valve replacement (TAVR) for severe aortic stenosis (AS) and to clarify their clinical implications for outcomes.
Methods
We retrospectively evaluated 550 consecutive patients with severe AS treated between January 2017 and August 2022. Patients with hemodialysis, valve‐in‐valve procedures, and unsuccessful procedures were excluded.
Results
The final study cohort included 514 patients who underwent successful TAVR (84 ± 5 years, 339 females). Female patients had a smaller physique and fewer atherosclerotic diseases, and chronic obstructive pulmonary diseases. Sizes of left ventricle and aortic valve were smaller in women even after the corrections by physique. Additionally, in women, left ventricular diastolic function indices such as eft atrial volume index (LAVI) and E/e’ were deteriorated, while left ventricular remodeling expressed by relative wall thickness (RWT) and the clinical AS stage were more advanced. There were no sex differences in 1‐year outcomes of TAVR. However, multiple regression analyses revealed that predictors for cardiovascular events in women were clinical frailty scale, LAVI and RWT (odds ratio [OR]: 1.57, p = 0.017; OR: 1.01, p = 0.020; OR: 45.21, p < 0.001; respectively), whereas predictors in men were atrial fibrillation and past smoking (OR: 4.01, p = 0.008; OR: 2.88, p = 0.049; respectively).
Conclusions
Women TAVR recipients had worse left ventricular diastolic function and left ventricular remodeling, which had significant impacts on the TAVAR outcomes. Early interventions may be beneficial especially for women.
Keywords: aortic stenosis, gender, outcome, transcatheter aortic valve replacement
Left ventricular diastolic function and remodeling played significant roles in TAVR outcomes in women. AF, atrial fibrillation; AOVA, aortic valve annulus; AS, aortic stenosis; BSA, body surface area; CFS, clinical frailty scale; CVS, cardiovascular; LA, left atrial; LAVI, left atrial volume index; LV, left ventricular; LVEDV, left ventricular end‐diastolic volume; LVEF, left ventricular ejection fraction; LVOT, left ventricular outflow trac; PAD, peripheral artery disease; SEV, self‐expandable valve; THV, transcatheter heart valve; RWT, relative wall thickness; TAVR, transcatheter aortic valve replacement
1. Introduction
Increased afterload in aortic stenosis (AS) burdens left ventricle with chronic pressure overload and leads to left ventricular dysfunction both in systole and diastole despite the development of compensatory left ventricular remodeling. As AS is a progressive degenerative heart disease, advanced stage of AS with severe valve stenosis has high mortality and morbidity [1].
Some sex differences have been reported in AS, including differences in clinical presentation as well as aortic valve and left ventricular morphology and function [2, 3, 4, 5]. Female AS patients have smaller left ventricular and aortic valvular anatomies than male patients beyond their smaller physiques. In women, reductions in daily physical activity are often unintentional or misattributed to age‐related changes, and these psychological or behavioral factors have been reported to contribute to sex differences in AS [6]. Moreover, females AS patients are often diagnosed later and are less likely to be referred for valve replacement.
Traditionally, women have poorer outcomes after surgical valve replacement (SAVR) [7]. On the contrary, outcomes after transcatheter aortic valve replacement (TAVR) have been reported to be comparable between sexes [2, 8, 9]. Nowadays. the use of TAVR is dramatically increasing all over the world especially in women [10]. Moreover, only a few studies have evaluated how sex‐related differences in clinical presentation and aortic valve and left ventricular structure and function affect TAVR outcomes. Therefore, this study aimed to determine whether sex differences exist in preoperative cardiac function among patients undergoing TAVR for AS.
2. Methods
The medical records of consecutive patients admitted to the Cardiology Department of Tokai University Hospital (Isehara, Kanagawa Prefecture, Japan) between February 2017 and September 2022 for TAVR for AS were retrospectively reviewed. The exclusion criteria were as follows: patients receiving hemodialysis or those with stage 5 chronic kidney disease, patients with unsuccessful procedures, and patients who died during the index hospitalization for TAVR. Medical background, laboratory data, transthoracic echocardiography (TTE) findings, and clinical outcomes were collected. Follow‐up data, including cardiovascular death and cardiovascular events—cardiovascular death or any rehospitalization due to cardiovascular disease—within 1 year after TAVR were also obtained. All TTE studies were performed in the medical ultrasound imaging laboratory or at the bedside with patients in the left lateral decubitus or supine position at admission. Routine imaging windows included parasternal, apical, and subxiphoid views. All baseline TTE measurements and analyses were performed in accordance with current echocardiographic guidelines [11, 12, 13, 14, 15]. Digital image datasets of comprehensive TTE examinations, including M‐mode, two‐dimensional, and Doppler images, were transferred to and archived in a hospital motion‐picture server. A cardiologist blinded to clinical information analyzed the TTE images in accordance with current echocardiographic guidelines. Staging of AS based on the extent of cardiac damage was evaluated as previously described [1]. Emergent TAVR was defined as a procedure performed during emergency hospitalization in patients admitted for cardiac arrest, acute decompensated heart failure with New York Heart Association class IV symptoms, acute chest pain, or syncope, as previously described [16].
Details of the TAVR procedure have been reported previously [17, 18]. The clinical indications for TAVR were determined by consensus during an institutional heart‐team conference. Preprocedural whole‐body computed tomography was performed in all cases. Balloon‐expandable SAPIEN 3 valves (Edwards Lifesciences, Irvine, CA, USA) and self‐expandable CoreValve Evolut R System, and CoreValve Evolut Pro Systems (Medtronic, Dublin, Ireland) were used.
The study protocol was approved by the Institutional Review Board of the Tokai University School of Medicine (Kanagawa, Japan) and adhered to the principles of the Declaration of Helsinki.
Numerical data are presented as mean ± standard deviation, or as median values with 25th–75th percentiles (interquartile range [IQR]) based on normality testing for continuous variables, and as counts for categorical variables. The Chi‐square test was used to analyze categorical variables. The unpaired Student's t‐test was used to compare parametric variables, whereas the Mann–Whitney U test was used for nonparametric variables. Logistic regression analysis was performed for multivariate analysis. We considered all parameters with values of p < 0.05 as covariate candidates for this analysis. Parameters were excluded from the analysis if >10% of the cohort had missing values. The cutoff values were calculated using receiver operating characteristic (ROC) curve analysis. Cumulative survival probability was evaluated using Kaplan–Meier plots. All statistical analyses were performed using JMP 14.0.0 (SAS Institute, Cary, NC, USA), and statistical significance was set at p < 0.05.
3. Results
During the study period, 550 patients with severe symptomatic AS underwent TAVR at our institute. Twenty‐four patients on hemodialysis or with stage 5 chronic kidney disease, nine who underwent a valve‐in‐valve procedure, two with failed procedures, and two who died during the index hospitalization (36 patients in total) were excluded. Thus, the final cohort comprised 514 patients who were hospitalized and underwent TAVR for symptomatic severe AS of the native aortic valve. The mean patient age was 84 ± 5 years, and 339 patients (70%) were women as shown in Figure 1.
FIGURE 1.
Patient inclusion flowchart CKD; chronic kidney disease, THV; transcatheter heart valve.
TAVR procedures were performed in 478 patients using the transfemoral approach (93%), 35 using the subclavicular approach (6.8%), and one using the left ventricular apical approach (0.2%). The average length of hospital stay after TAVR was 9.5 ± 10.6 days. No significant differences in these factors were observed between women and men. The characteristics of the transcatheter heart valves are shown in Figure 2. Women had significantly more self‐expanding valves than men (227/339 [67%] vs. 88/175 [51%], respectively; p = 0.001) (Figure 2a). Smaller self‐expanding and balloon‐expansion valves were used in women than in men (Figure 2b; p < 0.0001, respectively). During the index hospitalization for TAVR, 14 patients had cerebral infarction (2.7%), 11 had new permanent pacemaker implantation (2.1%), and one had acute myocardial infarction (0.2%). No difference was observed in the incidence of in‐hospital events between women and men.
FIGURE 2.
Types and sizes of tissue heart valves in this study. (a) Types. (b) Sizes. SE, self‐expandable valve; BE, balloon‐expandable valve.
Patient medical backgrounds are presented in Table 1. In the raw data, both men and women were of similar age. Significant differences were observed in body surface area (BSA), STS scores, atrial fibrillation, smoking history, previous myocardial infarction, carotid artery stenosis, peripheral arterial disease, chronic lung disease, hemoglobin levels, creatinine levels, and anticoagulant use.
TABLE 1.
Medical background.
| Female (n = 339) | Male (n = 175) | p value | |
|---|---|---|---|
| Age (years) | 84 ± 5 | 84± 5 | 0.411 |
| Body surface area (m2) | 1.38 ± 0.14 | 1.62± 0.16 | < 0.0001 |
| Body mass index (kg/m2) | 22.1 ± 3.8 | 22.7 ± 3.5 | 0.062 |
| NYHA functional class, point | 2.4 ± 0.6 | 2.3 ± 0.6 | 0.148 |
| Clinical frailty scale, point | 3.4 ± 0.9 | 3.3 ± 0.6 | 0.067 |
| STS Score, point | 8.3 ± 4.54 | 7.0 ± 5.4 | 0.005 |
| Aortic stenosis stage, point | 2.0 ± 0.8 | 1.7 ± 1.0 | < 0.001 |
| Atrial fibrillation, n (%) | 62 (19) | 50 (29) | 0.010 |
| Hypertension, n (%) | 262 (77) | 135 (77) | 0.970 |
| Past smoking, n (%) | 15 (4) | 68 (39) | < 0.0001 |
| Diabetes mellitus, n (%) | 91 (27) | 61 (35) | 0.059 |
| Dyslipidemia, n (%) | 198 (58) | 104 (59) | 0.823 |
| Chronic kidney disease, n (%) | 134 (42) | 70 (44) | 0.749 |
| Hemodialysis, n (%) | 0 (0) | 0 (0) | 0.000 |
| Pacemaker implantation, n (%) | 15 (4) | 13 (7) | 0.155 |
| Percutaneous coronary intervention, n (%) | 43 (13) | 32 (18) | 0.088 |
| Prior myocardial infarction, n (%) | 9 (3) | 15 (9) | 0.003 |
| Carotid artery stenosis, n (%) | 19 (6) | 35 (20) | < 0.0001 |
| Prior stroke, n (%) | 31 (9) | 20 (11) | 0.207 |
| Peripheral artery disease, n (%) | 16 (5) | 17 (9) | 0.029 |
| Chronic obstructive lung disease, n (%) | 5 (2) | 21 (12) | < 0.0001 |
| Hemoglobin (g/dL) | 11.4 ± 1.5 | 12.3 ± 1.8 | < 0.0001 |
| Creatinine (mg/dL) | 0.92 ± 0.33 | 1.23 ± 0.43 | < 0.0001 |
| eGFR (mL/dL/1.73 m2) | 50 ± 17 | 48 ± 15 | 0.338 |
| Albumin (g/dL) | 3.8 ± 0.7 | 3.8 ± 0.5 | 0.766 |
| Brain natriuretic peptide (pg/mL) [IQR] | 208 [97–491] | 190 [92–417] | 0.401 |
| Anticoagulants, n (%) | 36 (11) | 30 (17) | 0.020 |
| ACE inhibitor/ARB, n (%) | 129 (38) | 71 (41) | 0.579 |
| ARNI, n (%) | 4 (1) | 4 (1) | 0.579 |
| β‐blocker, n (%) | 84 (25) | 37 (21) | 0.357 |
| SGLT2 inhibitor, n (%) | 9 (3) | 10 (6) | 0.082 |
| MRA, n (%) | 33 (10) | 22 (13) | 0.374 |
| Statins, n (%) | 134 (40) | 66 (38) | 0.690 |
Abbreviations: ACE, angiotensin converting enzyme; ARB, angiotensin II receptor blocker; ARNI, angiotensin receptor neprilysin inhibitor; E, early left ventricular in‐flow velocity; e’, early mitral annulus velocity; eGFR, estimated glomerular filtration rate; IQR, interquartile range; LVDF, left ventricular diastolic function; MRA, mineralocorticoid receptor antagonist; NYHA, New York Heart Association; SGLT2, sodium/glucose cotransporter 2; STS, Society of Thoracic Surgeons. Bold text indicates statistical significance.
Table 2 shows echocardiographic parameters. Left atrial volume index (LAVI), left ventricular end‐diastolic volume index, left ventricular ejection fraction (LVEF), left ventricular outflow tract diameter, left ventricular outflow tract diameter/BSA, early diastolic mitral valve blood flow velocity (E), late diastolic mitral valve blood flow velocity (A), early diastolic mitral annulus velocity (e'), E/e', relative wall thickness (RWT), aortic valve annulus diameter, aortic valve annulus diameter/BSA, aortic valve peak systolic velocity, aortic valve mean pressure gradient, aortic regurgitation index, ascending aorta diameter, mitral annulus calcification, maximum TRPG, and the clinical stage of AS were significantly different between women and men.
TABLE 2.
Baseline echocardiography data.
| Female (n = 339) | Male (n = 175) | p value | |
|---|---|---|---|
| LAVI (mL/kg/m2) | 55 ± 29 | 47 ± 21 | 0.001 |
| LVEDVI (mL/kg/m2) | 52 ± 18 | 57 ± 20 | 0.001 |
| LVEF (%) | 65± 12 | 62 ± 13 | < 0.001 |
| SVI (mL/kg/m2) | 41 ± 11 | 39 ± 10 | 0.054 |
| LVOT diameter (mm) | 18 ± 2 | 20 ± 2 | < 0.0001 |
| LVOT diameter/BSA | 13.3 ± 1.9 | 12.6 ± 1.7 | < 0.001 |
| E wave (cm/s) | 82 ± 34 | 75 ± 29 | 0.017 |
| A wave (cm/s) | 110 ± 30 | 92 ± 28 | < 0.0001 |
| E/A | 0.77 ± 0.49 | 0.84 ± 0.55 | 0.160 |
| Deceleration time (ms) | 270 ± 107 | 258 ± 93 | 0.187 |
| e’ (cm/s) | 4.1 ± 1.5 | 4.5 ± 1.5 | 0.006 |
| E/e’ | 22 ± 12 | 18 ± 8 | < 0.0001 |
| LVMI (g/m2) | 149 ± 44 | 153 ± 48 | 0.288 |
| RWT | 0.56 ± 0.13 | 0.51 ± 0.13 | < 0.0001 |
| Aortic annulus diameter (mm) | 19 ± 2 | 21 ± 3 | < 0.0001 |
| Aortic annulus diameter/BSA | 14.2 ± 1.8 | 13.3 ± 2.0 | < 0.0001 |
| Aortic valve peak systolic velocity (m/s) | 4.6 ± 0.8 | 4.3 ± 0.7 | < 0.001 |
| Aortic valve mean pressure gradient (mm Hg) | 47 ± 19 | 41 ± 15 | 0.001 |
| Aortic valve area index (cm2/kg/m2) | 0.40 ± 0.12 | 0.39 ± 0.11 | 0.654 |
| Aortic regurgitation index, point | 1.8 ± 0.8 | 1.8 ± 0.8 | 0.043 |
| Mitral annulus calcification, n (%) | 133 (54) | 35 (27) | < 0.0001 |
| Mitral regurgitation index, point | 1.8 ± 0.8 | 1.8 ± 0.8 | 0.734 |
| RVFAC, % | 48 ± 10 | 46 ± 9 | 0.022 |
| Tricuspid regurgitation index, point | 1.7 ± 0.7 | 1.6 ± 0.7 | 0.130 |
| Maximum TRPG (mm Hg) | 27 ± 10 | 25 ± 8 | 0.045 |
| Systolic pulmonary artery pressure (mm Hg) | 31 ± 10 | 29 ± 9 | 0.097 |
| Right atrial pressure (mm Hg) | 3.5 ± 1.8 | 3.8 ± 2.5 | 0.132 |
| Aortic stenosis stage, point | 2.0 ± 0.8 | 1.7 ± 1.0 | < 0.001 |
Abbreviations: A, left ventricular in‐flow velocity during atrial contraction; E, early left ventricular in‐flow velocity; e’, early mitral annulus velocity; LAVI, left atrial volume index; LVEDVI, left ventricular end‐diastolic volume index; LVEF, left ventricular ejection fraction; LVMI, left ventricular mass index; LVOT, left ventricular outflow; RVFAC, right ventricular fractional area change; RWT, relative wall thickness; SVI, stroke volume index; TRPG, tricuspid regurgitation pressure gradient.
Bold text indicates statistical significance.
One‐year outcomes of TAVR are shown in Table 3. In the raw data, 26 patients experienced all‐cause death (5.1%), 12 had cardiovascular death (2.3%), 49 had cardiovascular events (9.5%), 10 had cerebral infarction (1.9%), 7 had new permanent pacemaker implantation (1.4%), and 16 had heart failure rehospitalization (3.1%). No differences were observed in the incidence of 1‐year outcomes between women and men.
TABLE 3.
One‐year outcomes.
| Female (n = 339) | Male (n = 175) | p value | |
|---|---|---|---|
| All‐cause death, n (%) | 14 (4) | 12 (7) | 0.181 |
| Cardiovascular death, n (%) | 6 (2) | 6 (3) | 0.238 |
| Cardiovascular events, n (%) | 35 (10) | 19 (11) | 0.852 |
| Permanent pacemaker implantation, n (%) | 6 (2) | 1 (1) | 0.267 |
| Cerebral infarctions, n (%) | 6 (2) | 4 (2) | 0.688 |
| Heart failure hospitalization, n (%) | 11 (3) | 5 (3) | 0.811 |
Table 4 lists medical background factors predicting cardiovascular events in women and men, as determined via logistic regression analysis. In the cohort of women, clinical frailty scale (CFS) predicted cardiac events (odds ratio [OR]: 1.57, 95% confidence interval [CI] 1.07–2.27, p = 0.017). On the other hand, in the cohort of men, the presences of atrial fibrillation and past smoking predicted cardiac events (OR: 4.01, 95% CI 1.42–11.26, p = 0.008; OR: 2.88, 95% CI 1.01–8.23, p = 0.049; respectively). Table 5 lists echocardiographic parameters predicting cardiovascular events in women and men, as determined via logistic regression analysis. In the cohort of women, LAVI and RWT predicted cardiac events (OR: 1.01, 95% CI 1.00–1.03, p = 0.020; OR: 45.21, 95% CI 2.38–859.42, p < 0.001; respectively). On the other hand, in the cohort of men, no parameters predicted cardiac events.
TABLE 4.
Medical background factors predicting cardiovascular events.
| Female cohort (n = 339): 35 events | Male cohort (n = 175): 19 events | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| univariate | multivariate | univariate | multivariate | |||||||||
| OR | 95% CI | p value | OR | 95% CI | p value | OR | 95% CI | p value | OR | 95% CI | p value | |
| Age | 1.09 | 1.02–1.18 | 0.018 | 1.05 | 0.97–1.14 | 0.241 | ||||||
| Clinical frailty scale | 1.73 | 1.24–2.42 | 0.001 | 1.57 | 1.07–2.27 | 0.017 | 1.83 | 1.01–3.28 | 0.035 | 1.75 | 0.97–3.15 | 0.077 |
| STS Score | 1.08 | 1.02–1.16 | 0.013 | 1.03 | 0.96–1.11 | 0.388 | ||||||
| Atrial fibrillation | 2.22 | 1.02–4.81 | 0.043 | 2.07 | 0.90–4.53 | 0.074 | 3.22 | 1.22–8.67 | 0.018 | 4.01 | 1.42‐ 11.26 | 0.008 |
| Past smoking | 3.06 | 1.17–8.65 | 0.026 | 2.88 | 1.01–8.23 | 0.049 | ||||||
Note: Bold text indicates statistical significance.
Abbreviation: STS, Society of Thoracic Surgeons.
TABLE 5.
Echocardiographic parameters predicting cardiovascular events.
| Female cohort (n = 339): 35 events | Male cohort (n = 175): 19 events | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| univariate | multivariate | univariate | multivariate | |||||||||
| OR | 95% CI | p value | OR | 95% CI | p value | OR | 95% CI | p value | OR | 95% CI | p value | |
| LAVI | 1.01 | 1.00–1.02 | 0.010 | 1.01 | 1.00–1.03 | 0.020 | ||||||
| LVEF | 1.04 | 1.00–1.08 | 0.031 | 1.03 | 0.99–1.07 | 0.127 | ||||||
| E/e’ | 1.05 | 1.02–1.07 | < 0.001 | 1.03 | 1.00–1.06 | 0.105 | 1.04 | 0.99–1.09 | 0.100 | |||
| RWT | 27.18 | 2.60–283.57 | 0.006 | 45.21 | 2.38–859.42 | < 0.001 | ||||||
Note: Bold text indicates statistical significance.
Abbreviations: E, early left ventricular in‐flow velocity; e’, early mitral annulus velocity; LAVI, left atrial volume index; LVEF, left ventricular ejection fraction; RWT, relative wall thickness.
In the female cohort, ROC curve analyses of CFS, LAVI and RWT demonstrated significant prediction for cardiovascular events (p = 0.001, area under the curve [AUC]: 0.59074, cutoff value: 5.0; p = 0.012, AUC: 0.66635, cutoff value: 49.2 mL/m2, p = 0.006, AUC: 0.63398, cutoff value: 0.62, respectively). As shown in Figure 3a–c, Kaplan–Meier cumulative survival curves demonstrated no differences between men and women in all‐cause death, cardiovascular death, or cardiovascular events. In the female cohort, patients with lower CFS, LAVI and RWT values had better cardiovascular events–free survival, as indicated by the log‐rank test (p < 0.0001, p = 0.01, p = 0.01, respectively), as shown in Figure 3d–f. In the male cohort, patients without atrial fibrillation and past smoking had better cardiovascular event–free survival, as indicated by the log‐rank test (p = 0.009, p = 0.020, respectively), as shown in Figure 3g–h.
FIGURE 3.
Cumulative survival probability plots 1 year after transcatheter aortic valve replacement using the Kaplan–Meier method. (a) All‐cause death in the whole cohort divided by sex. (b) Cardiovascular death in the whole cohort divided by sex. (c) Cardiovascular events in the whole cohort divided by sex. (d) Cardiovascular events in women divided by frailty. (e) Cardiovascular events in women divided by left atrial volume index. (f) Cardiovascular events in women divided by relative wall thickness. (g) Cardiovascular events in men divided by the presence of atrial fibrillation. (h) Cardiovascular events in men divided by the presence of past smoking. AF, atrial fibrillation; CFS, clinical frailty scale; LAVI. Left atrial volume index; LV, left ventricular; RWT, relative wall thickness; TAVR, transcatheter aortic valve replacement.
4. Discussion
In this study, we examined gender differences in preoperative cardiac function in patients who underwent TAVR for AS and their impact on TAVR outcomes. The main findings of this study are as follows: (1) There were several sex differences observed in medical background such as patient's physique as expressed by BSA and comorbid diseases such as atherosclerotic vascular disorders. Moreover, TTE parameters such as the sizes of left ventricle and aortic valve were smaller in women even after the corrections by BSA. Furthermore, left ventricular diastolic function indices such as LAVI and E/e’ were deteriorated in women as well as the AS stage, despite the higher LVEF: (2) Although there were no sex differences in 1‐year outcomes of TAVR, predictors for cardiovascular events in women, which were selected as clinical frailty scale, LAVI and RWT, were different from those in men selected as the presences of atrial fibrillation and past smoking.
Sex differences, observed in medical background and the sizes of chambers and valves in this study, were consistent with previous studies [3]. Notably, left ventricular diastolic function and the stage of AS were further deteriorated in women than in men. It has been reported that left ventricular fibrosis progresses in women due to early activation of the renin–angiotensin–aldosterone system in AS [19, 20]. This may be one of the reasons for the deteriorated left ventricular diastolic dysfunction in women. In this study, we evaluated the clinical stage of AS, which was not examined in previous studies, and confirmed that women TAVR recipients had more advanced clinical AS stages. This may represent a novel finding of our study.
Traditionally, women have been thought to have outcomes roughly similar to those of men after TAVR [1, 7, 8]. In recent years, as the indications for TAVR in AS have expanded [21, 22], new sex differences in outcomes have been reported. However, women are considered to have inferior in‐hospital outcomes [23], different results have been reported regarding long‐term outcomes. Zhou analyzed large US readmission data and found that older women had a higher risk of readmission within 6 months of discharge after TAVR [24], whereas a large Swedish study reported a better long‐term prognosis for women up to 10 years after discharge [25]. In Japan, the prognosis at 1 year after surgery is reported to be favorable for women [26]. In this study, there was no sex differences were observed in TAVR outcomes. However, left ventricular diastolic function and the stage of AS were further deteriorated in women than in men. Moreover, one of the left ventricular diastolic function indices such as LAVI and one of the left ventricular remodeling indices such as RWT were predictors for cardiovascular events in women. Therefore, more profound left ventricular diastolic dysfunction in women TVAR recipients might have impacted on the 1‐year outcomes after TAVR. We postulate that women AS patients could have better outcomes than men if their left ventricular diastolic function was less impaired and the clinical AS stage was earlier and similar to men at the time of TAVR. Thus, sex differences in TAVR recipients may attenuate the clinical benefits of TVAR therapy, and early interventions may be beneficial especially for women in this study.
The fact that women accounted for approximately twice the number of TAVR patients compared with men in this study may align with previous reports indicating that TAVR has become more common in women in recent years [9]. Therefore, interventional treatment for female AS appears to have become more active at this medical center. However, this may also suggest that psychological, behavioral, and sociological selection biases in AS management between men and women [5] may have existed in this study.
The limitations of this study include the small number of cases and the possibility that gender‐based differences were not detected. Low event rates may have been insufficient to observe gender differences in outcomes. Moreover, the limited follow‐up period of 1 year might undercount the frequency of cardiac events. However, we believe that most events have happened in the first year after TAVAR. Furthermore, as this is a single‐center study, institutional bias may exist, and case selection bias may arise, because it is a retrospective observational study. For these reasons, generalization of the results is difficult; however, they may be useful for generating hypotheses to be examined in future large‐scale studies.
5. Conclusion
In patients who underwent TAVR for AS, we investigated sex differences in baseline characteristics and cardiac function. Although there were no sex differences in 1‐year outcomes of TAVR, predictors for cardiovascular events were different between women and men. Baseline left ventricular diastolic function and left ventricular remodeling played significant roles in TAVR outcomes in women. Therefore, early interventions may be beneficial especially for women. Further long‐term follow‐up and larger multicenter studies incorporating psychological, behavioral, and sociological perspectives are needed to clarify this important issue.
Conflicts of Interest
Dr. Ohno has served as a proctor for Medtronic. Dr. Kamioka has served as a proctor for Edwards Life Sciences.
Ethics Statement
The study protocol was approved by the Institutional Review Board for Clinical Research of the Tokai University School of Medicine (19R028‐001 H). This study was conducted in accordance with the principles outlined in the Declaration of Helsinki. The requirement for written informed consent was waived, because of the low‐risk nature of the study. An opt‐out approach was employed.
Acknowledgments
The authors have nothing to report.
Data Availability Statement
The datasets generated and analyzed in this study are not publicly available because of patient privacy concerns.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated and analyzed in this study are not publicly available because of patient privacy concerns.