
==== Front
Interdiscip Cardiovasc Thorac Surg
Interdiscip Cardiovasc Thorac Surg
icvts
Interdisciplinary Cardiovascular and Thoracic Surgery
2753-670X
Oxford University Press

39128016
10.1093/icvts/ivae140
ivae140
Valvular Heart Disease
Original Article
Editor's Choice
Eacts/121
Eacts/125
AcademicSubjects/MED00920
Sex-related differences among patients undergoing surgical aortic valve replacement—a propensity score matched study
Zierer Andreas Department of Cardiac, Vascular and Thoracic Surgery, Kepler University Hospital Linz, Linz, Austria
Department of Cardiac, Vascular and Thoracic Surgery, Hospital Wels-Grieskirchen, Wels, Austria

De Paulis Ruggero Department of Cardiac Surgery, European Hospital, Rome, Italy

https://orcid.org/0000-0002-3042-7182
Bakhtiary Farhad Department of Cardiac Surgery, University Hospital Bonn, Bonn, Germany

Ahmad Ali El-Sayed Department of Cardiac Surgery, University Hospital Bonn, Bonn, Germany

https://orcid.org/0000-0003-4950-5432
Andreas Martin Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria

Autschbach Rüdiger Department of Thoracic and Cardiovascular Surgery, University Hospital RWTH Aachen, Aachen, Germany

Benedikt Peter Department of Cardiac, Vascular and Thoracic Surgery, Kepler University Hospital Linz, Linz, Austria
Department of Cardiac, Vascular and Thoracic Surgery, Hospital Wels-Grieskirchen, Wels, Austria

Binder Konrad Department of Cardiac Surgery, University Hospital St Poelten, St Poelten, Austria

https://orcid.org/0000-0002-7656-5812
Bonaros Nikolaos Department of Cardiac Surgery, Medical University of Innsbruck, Innsbruck, Austria

Borger Michael Department of Cardiac Surgery, Leipzig Heart Center, Leipzig, Germany

Bourguignon Thierry Department of Cardiology and Cardiac Surgery, Tours University Hospital, Tours, France

Canovas Sergio Cardiovascular Surgery Department, Hospital University Virgen de la Arrixaca, Murcia, Spain

Coscioni Enrico Department of Cardiac Surgery, University Hospital San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy

Dagenais Francois Department of Cardiac Surgery, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec City, Québec, Canada

Demers Philippe Department of Surgery, Montreal Heart Institute, University of Montreal, Montreal, Canada

Dewald Oliver Department of Pediatric Cardiac Surgery, University Hospital Erlangen, Erlangen, Germany

Feyrer Richard Department of Cardiac Surgery, Clinic for Cardiovascular Surgery, Central Military Hospital, Koblenz, Germany

Geißler Hans-Joachim Department of Cardiac, Vascular and Thoracic Surgery, Kepler University Hospital Linz, Linz, Austria
Department of Cardiac, Vascular and Thoracic Surgery, Hospital Wels-Grieskirchen, Wels, Austria

Grabenwöger Martin Department of Cardiovascular Surgery, Clinic Floridsdorf, Vienna, Austria

Grünenfelder Jürg Department of Cardiac Surgery, Heart Clinic Zurich, Hirslanden Klinik, Zurich, Switzerland

https://orcid.org/0000-0002-1019-1432
Kueri Sami Department of Cardiovascular Surgery, University Heart Center Freiburg Bad Krozingen, Bad Krozingen, Germany

https://orcid.org/0000-0003-0312-4802
Lam Ka Yan Department of Cardiothoracic Surgery, Catharina Hospital Eindhoven, Eindhoven, Netherlands

Langanay Thierry Department of Thoracic and Cardiovascular Surgery, Rennes University Hospital Center, Rennes, France

Laufer Günther Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria

Van Leeuwen Wouter Department of Cardiothoracic Surgery, Erasmus MC University Medical Center, Rotterdam, Netherlands

Leyh Rainer Department of Thoracic and Cardiovascular Surgery, University of Wuerzburg, Wuerzburg, Germany

https://orcid.org/0000-0002-9687-1841
Liebold Andreas Department of Cardiac Surgery, University of Ulm Medical Center, Ulm, Germany

Mariscalco Giovanni Department of Cardiac Surgery, National Institute for Health Research Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK

Massoudy Parwis Department of Cardiac Surgery, Klinikum Passau, Passau, Germany

Mehdiani Arash Department of Cardiac Surgery, University Hospital Duesseldorf, Duesseldorf, Germany
Department of Thoracic and Cardiovascular Surgery, West-German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany

Pessotto Renzo Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK

Pollari Francesco Department of Cardiac Surgery, Klinikum Nürnberg-Paracelsus Medical University, Nuremberg, Germany

Polvani Gianluca Department of Cardiovascular Surgery, Centro Cardiologico Monzino IRCCS, Milan, Italy

Ricci Alessandro Department of Cardiac Surgery, European Hospital, Rome, Italy

https://orcid.org/0000-0003-3928-6977
Roussel Jean-Christian Department of Thoracic and cardiovascular surgery, CHU Nantes, Nantes, France

Salamate Saad Department of Cardiac Surgery, University Hospital Bonn, Bonn, Germany

https://orcid.org/0000-0003-3305-9343
Siepe Matthias Department of Cardiovascular Surgery, University Heart Center Freiburg Bad Krozingen, Bad Krozingen, Germany
Department of Cardiac Surgery, University Hospital Bern, University of Bern, Bern, Switzerland

https://orcid.org/0000-0001-8338-3016
Stefano Pierluigi Department of Cardiothoracic and Vascular Surgery, Careggi University Hospital, Florence, Italy

Strauch Justus Department of Cardiothoracic Surgery, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Bochum, Nordrhein-Westfalen, Germany

https://orcid.org/0000-0001-9453-9039
Theron Alexis Cardio-Thoracic Surgery Department, Hospital de la Timone, Marseille, France

https://orcid.org/0000-0001-6841-4208
Vötsch Andreas Department of Cardiovascular and Endovascular Surgery, Paracelsus Medical University, Salzburg, Austria

Weber Alberto Department of Cardiovascular Surgery, Heart Center Hirslanden, Zurich, Switzerland

https://orcid.org/0000-0002-7494-5774
Wendler Olaf Department of Cardiothoracic Surgery, King’s College Hospital NHS Foundation Trust, London, UK

Thielmann Matthias Department of Thoracic and Cardiovascular Surgery, West-German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany

Eden Matthias Department of Medicine III: Cardiology, Angiology, and Pneumology, Heidelberg University, Heidelberg, Germany

Botta Beate Institute for Pharmacology and Preventive Medicine, Cloppenburg, Germany

https://orcid.org/0000-0003-4970-2110
Bramlage Peter Institute for Pharmacology and Preventive Medicine, Cloppenburg, Germany

https://orcid.org/0000-0001-9176-293X
Meuris Bart Department of Cardiac Surgery, University Hospitals Leuven, Leuven, Belgium

Prof. Andreas F. Zierer, Kepler University, Hospital Linz, Krankenhausstraße 9, 4021 Linz, Austria, Tel: +43 (0)5 7680 83 - 2136, Email: andreas.zierer@kepleruniklinikum.at
8 2024
10 8 2024
10 8 2024
39 2 ivae14002 7 2024
08 8 2024
22 8 2024
© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.
2024
https://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Graphical abstract

Surgical aortic valve replacement (SAVR) has been the gold standard treatment for aortic stenosis (AS) for decades [1].

Abstract

OBJECTIVES

We investigated the sex-related difference in characteristics and 2-year outcomes after surgical aortic valve replacement (SAVR) by propensity-score matching (PSM).

METHODS

Data from 2 prospective registries, the INSPIRIS RESILIA Durability Registry (INDURE) and IMPACT, were merged, resulting in a total of 933 patients: 735 males and 253 females undergoing first-time SAVR. The PSM was performed to assess the impact of sex on the SAVR outcomes, yielding 433 males and 243 females with comparable baseline characteristics.

RESULTS

Females had a lower body mass index (median 27.1 vs 28.0 kg/m2; P = 0.008), fewer bicuspid valves (52% vs 59%; P = 0.036), higher EuroSCORE II (mean 2.3 vs 1.8%; P < 0.001) and Society of Thoracic Surgeons score (mean 1.6 vs 0.9%; P < 0.001), were more often in New York Heart Association functional class III/IV (47% vs 30%; P < 0.001) and angina Canadian Cardiovascular Society III/IV (8.2% vs 4.4%; P < 0.001), but had a lower rate of myocardial infarction (1.9% vs 5.2%; P = 0.028) compared to males. These differences vanished after PSM, except for the EuroSCORE II and Society of Thoracic Surgeons scores, which were still significantly higher in females. Furthermore, females required smaller valves (median diameter 23.0 vs 25.0 mm, P < 0.001). There were no differences in the length of hospital stay (median 8 days) or intensive care unit stay (median 24 vs 25 hours) between the 2 sexes. At 2 years, post-SAVR outcomes were comparable between males and females, even after PSM.

CONCLUSIONS

Despite females presenting with a significantly higher surgical risk profile, 2-year outcomes following SAVR were comparable between males and females.

Aortic stenosis
Surgical aortic valve replacement
Sex disparities
Edwards Lifesciences 10.13039/100006520 Institute for Pharmacology and Preventive Medicine, Cloppenburg, Germany
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pmcINTRODUCTION

Surgical aortic valve replacement (SAVR) has been the gold standard treatment for aortic stenosis (AS) for decades [1]. However, a precise understanding of specific sex-related differences in baseline characteristics and post-SAVR long-term outcomes and safety remains a matter of debate [2, 3]. Although women and men share a similar prevalence of AS, SAVR is less often performed in female patients. Specific anatomical characteristics peculiar to women's hearts, such as smaller valvular size and aortic annulus/root and left ventricular outflow tract dimensions, make it technically more complicated and challenging for SAVR in women [4]. Besides, factors such as advanced age, greater frailty, smaller body size and the presence of more non-atherosclerotic comorbidities place females in a high-risk category for SAVR [3, 5, 6].

Several studies indicated that women undergoing SAVR experience worse short-term outcomes, including more in-hospital and 30-day deaths, more vascular complications and blood transfusions and increased length of hospital stays [2, 7] compared to men [2, 3, 6, 8]. Although comparable long-term survival after SAVR was observed among both sexes [8, 9], extensive research is imperative to elucidate the male-female differences in the baseline characteristics and clinical outcomes to optimize the treatment for aortic valve diseases.

PATIENTS AND METHODS

In the present analysis, we combined data from 2 prospective, observational, multicentre registries— the INSPIRIS RESILIA Durability Registry (INDURE) and the IMPACT registry [10, 11], to study the sex-related differences in SAVR outcomes. Our goal was to report 2-year follow-up data of male and female patients undergoing SAVR using propensity score matching (PSM).

Ethics statement

The study was approved by the institutional review board/ethics committee at each participating centre (Supplementary Material, Table S1). Written informed consent was obtained from each patient before enrolment.

Patient population

Adult patients over 18 years of age undergoing SAVR and receiving the Edwards INSPIRIS RESILIA bioprosthesis were enrolled in the registries. In addition, patients undergoing a planned native valve replacement with or without combined aortic root replacement and/or coronary artery bypass graft (CABG) based on the preprocedural evaluation were included. Exclusion criteria included prior myocarditis within 3 months before SAVR and a double valve procedure (replacement and repair). Additionally, when a valve implant was not possible as per device instruction for use, individuals with a life expectancy <12 months and patients who were pregnant at the time of the operation were excluded.

Objectives

The primary objective of the analysis was to compare baseline and procedural characteristics of male and female patients undergoing SAVR.

The secondary objective was to compare the sex-related differences in post-SAVR clinical outcomes as defined by the Valve Academic Research Consortium-2 [12] at the 2-year follow-up, which includes incidence of all-cause mortality, prosthetic endocarditis, thromboembolic events (stroke/transient ischaemic attack), life-threatening valve-related bleeding, repeat procedure requirement and a permanent pacemaker implant (PPI).

Statistical analyses

Data were analysed using descriptive statistics, with categorical variables presented as absolute values and frequencies (%) and the continuous variables presented as means (standard deviation) and/or median [interquartile range (IQR)]. The percentages were calculated based on the number of patients with valid data per parameter, i.e. excluding patients with missing information. Comparisons were performed using a t-test or the Mann–Whitney U test for continuous variables, depending on distribution, and a Fisher exact or a χ2 test for categorical variables. Propensity scores (PS) were calculated using a generalized linear model to assess the sex-specific effects (male vs female). The following covariates were selected to calculate the PS: body mass index, valve morphology, New York Heart Association (NYHA) functional class III/IV, Canadian Cardiovascular Society (CCS) angina III/IV, diabetes mellitus, hypertension, left ventricular ejection fraction, mean transvalvular pressure gradient, previous percutaneous intervention, pacemaker, chronic obstructive pulmonary disease, dialysis, aortic valve regurgitation (moderate/severe), myocardial infarction, transient ischaemic attack/stroke, peripheral arterial disease and coronary artery disease. The 1:2 ratio matching was performed using nearest neighbour matching with a calliper width equal to 0.2 times the standard deviation of the PS logit. Post-matching, standardized mean differences were analysed for all covariates included in the PS calculation. The mean differences for all covariates post-matching were within a desirable threshold (±0.1), indicating adequate balance. Statistical analyses were performed using R version 4.3 (https://www.R-project.org/).

RESULTS

A total of 993 patients, 735 males and 253 females, who underwent SAVR using the INSPIRIS RESILIA between 2019 and 2021 comprised the entire cohort. To assess the impact of sex on SAVR outcomes, a PSM cohort was created, resulting in a total of 676 matched pairs of 433 males and 243 females (Fig. 1).

Figure 1: Study flow chart. CABG: coronary artery bypass graft; PS: propensity score; SAVR: surgical aortic valve replacement.

*Reasons: Not meeting inclusion/exclusion criteria (n = 9); not receiving INSPIRIS RESILIA valve (n = 10); double valve procedure (replacement or repair; n = 10); withdrew from the study (n = 2).

Patient characteristics

In the entire cohort, the female patients had a lower BMI [median 27.1 (IQR 23.4–31.0) vs 28.0 kg/m2 (IQR 25.2–31.0); P = 0.008] and were less likely to have bicuspid valves (52% vs 59%; P = 0.036) compared to the male patients (Table 1). Additionally, females exhibited a higher prevalence of advanced NYHA functional class III/IV symptoms (47% vs 30%; P < 0.001) and angina CCS class III/IV symptoms (8.2% vs 4.4%; P = 0.019), indicating a higher symptomatic burden at baseline. However, after PSM, the differences were not significant in any of the cases.

Table 1: Patient characteristics

	Full cohort	PS matched cohort	
Mean ± SD or median (IQR) or n (%)	Male, N = 735	Female, N = 258	SMD	95% CI	P-value	Male, N = 433	Female, N = 243	SMD	95% CI	P-value	
Age, years	58.8 ± 9.2	59.8 ± 9.5	−0.11	−0.25, 0.03	0.159	59.0 ± 9.7	59.8 ± 9.5	−0.09	−0.24, 0.07	0.430	
Body mass index, kg/m2	28.0 (25.2–31.0)	27.1 (23.4–31.0)	0.11	−0.03, 0.25	0.008	27.1 (24.7–30.2)	27.3 (23.5–31.3)	−0.05	−0.20, 0.11	0.601	
Valve morphology			0.15	0.01, 0.29	0.036			0.04	−0.12, 0.19	0.647	
 Bicuspid	434 (59)	133 (52)				236 (55)	128 (53)				
 Tricuspid	301 (41)	125 (48)				197 (45)	115 (47)				
NYHA functional class III/IV	220 (30)	121 (47)	0.36	0.22, 0.50	<0.001	169 (39)	110 (45)	0.13	−0.03, 0.28	0.114	
Angina CCS III/IV	32 (4.4)	21 (8.2)	0.16	0.02, 0.30	0.019	22 (5.1)	17 (7.0)	0.08	−0.08, 0.24	0.306	
EuroSCORE II, %	1.8 ± 2.0	2.3 ± 3.1	−0.18	−0.32, −0.04	<0.001	1.6 ± 1.7	2.4 ± 3.0	−0.18	−0.32, −0.04	<0.001	
STS score, %	0.9 ± 2.5	1.6 ± 2.2	−0.31	−0.46, −0.17	<0.001	1.0 ± 2.3	1.7 ± 2.0	−0.33	−0.48, −0.17	<0.001	
Medical history											
 Diabetes mellitus	115 (16)	45 (17)	0.05	−0.09, 0.19	0.500	73 (17)	42 (17)	0.01	−0.15, 0.17	0.888	
 Systemic hypertension	438 (60)	148 (57)	0.05	−0.10, 0.19	0.531	243 (56)	138 (57)	0.01	−0.14, 0.17	0.866	
 Coronary artery disease	504 (69)	192 (75)	0.14	−0.01, 0.28	0.068	313 (72)	180 (74)	0.04	−0.12, 0.20	0.616	
 Myocardial infarction	38 (5.2)	5 (1.9)	0.18	0.03, 0.32	0.028	11 (2.5)	5 (2.1)	0.03	−0.12, 0.19	0.692	
 Peripheral vascular disease	43 (5.9)	11 (4.3)	0.07	−0.07, 0.21	0.334	21 (4.8)	11 (4.5)	0.02	−0.14, 0.17	0.849	
 TIA/stroke	36 (4.9)	13 (5.0)	0.01	−0.14, 0.15	0.928	19 (4.4)	11 (4.5)	0.01	−0.15, 0.16	0.933	
 COPD	52 (7.1)	27 (10)	0.12	−0.02, 0.26	0.083	35 (8.1)	22 (9.1)	0.03	−0.12, 0.19	0.663	
 PPI	13 (1.8)	4 (1.6)	0.02	−0.12, 0.16	1.000	8 (1.8)	4 (1.6)	0.02	−0.14, 0.17	1.000	
 Previous PCI	78 (11)	19 (7.4)	0.11	−0.03, 0.26	0.131	35 (8.1)	19 (7.8)	0.01	−0.15, 0.17	0.903	
 Dialysis	8 (1.1)	2 (0.8)	0.03	−0.11, 0.17	1.000	5 (1.2)	2 (0.8)	0.03	−0.12, 0.19	1.000	
Echocardiography											
 AV regurgitation (moderate/severe)	255 (35)	68 (27)	0.18	0.04, 0.32	0.015	128 (30)	66 (27)	0.05	−0.10, 0.21	0.508	
 LVEF, %	58 ± 10	60 ± 10	−0.28	−0.43, −0.14	<0.001	60 ± 9	60 ± 10	−0.04	−0.20, 0.12	0.464	
 Mean transvalvular pressure gradient, mmHg	43 ± 20	46 ± 21	−0.16	−0.30, −0.01	0.249	45 ± 18	46 ± 21	−0.05	−0.21, 0.12	0.690	
AV: aortic valve; CCS: Canadian Cardiovascular Society; EuroSCORE: European System for Cardiac Operative Risk Evaluation; CI; confidence interval; COPD: chronic obstructive pulmonary disease; IQR: interquartile range; LVEF: left ventricular ejection fraction; NYHA: New York Heart Association; PCI: percutaneous intervention; PPI: permanent pacemaker implant; PS: propensity score; SD: standard deviation; SMD: standard mean difference; STS: Society of Thoracic Surgeons; TIA: transient ischaemic attack.

Compared to males, female patients in both cohorts exhibited significantly higher surgical risk with higher EuroSCORE II (2.3 ± 3.1% vs 1.8 ± 2.0%; P < 0.001) and Society of Thoracic Surgeons (STS) score (1.6 ± 2.2% vs 0.90 ± 2.5%; P < 0.001). Notably, these differences persisted after PSM (EuroSCORE II: 2.4 ± 3.0% vs 1.6 ± 1.7%; P < 0.001 and STS score: 1.7 ± 2.0% vs 1.0 ± 2.3%; P < 0.001). In the entire cohort, females had a lower history of myocardial infarction (1.9% vs 5.2%; P = 0.028) than males.

In baseline echocardiography, females exhibited a lower prevalence of moderate to severe aortic valve regurgitation (27% vs 35%; P = 0.015), along with a better left ventricular ejection fraction (60 ± 10% vs 58 ± 10%; P < 0.001) and slightly higher mean transvalvular pressure gradients (46 ± 21 vs 43 ± 20 mmHg; P = 0.249) compared to males. This trend did not persist after PSM.

Procedural characteristics

In our study, both females and males had distinct AS aetiologies (P = 0.047), primarily showing congenital AS (51.6% in females vs 59.8% in males) followed by degenerative AS (44.6% vs 37.1%) (Supplementary Material, Table S2).

In the total cohort, minimally invasive surgery was more frequent in females (46.5% vs 38.6%; P = 0.027) with less concomitant CABG (10.9% vs 16.3%; P = 0.034) (Supplementary Material, Table S2). Notably, these differences disappeared after PSM (Table 2). Females required smaller valves [median 23.0 mm (IQR 21.0–23.0)] compared to males [median 25.0 mm (IQR 23.0–27.0)], which was significant in both total and PSM cohorts (P < 0.001). The majority of female patients received either 23- (44.4%) or 21- (39.9%) mm valves, whereas male patients received either 25- (37.2%) or 23- (30.7%) mm valves. There were no differences in the overall procedural time (skin-to-skin) between males and females in the matched cohort (P = 0.170). The first implant attempt was successful in both sexes (>99.0%), with no intraprocedural deaths.

Table 2: Procedural details—propensity score matched cohort

Mean ± SD or median (IQR) or n (%)	Male, N = 433	Female, N = 243	P-value	
Aetiology of valve pathology			0.769	
 Congenital	239 (55.3)	128 (52.7)		
 Degenerative	183 (42.4)	106 (43.6)		
 Endocarditic	1 (0.2)	1 (0.4)		
 Rheumatic	2 (0.5)	2 (0.8)		
 None (no aortic stenosis)	7 (1.6)	6 (2.5)		
Isolated AVR	259 (59.8)	149 (61.3)	0.702	
MIS	178 (41.1)	114 (46.9)	0.144	
Concomitant procedures				
 CABG	67 (15.5)	27 (11.1)	0.116	
 Root replacement	31 (7.2)	11 (4.5)	0.174	
 Supracoronary tube graft	58 (13.4)	31 (12.8)	0.814	
Total operation time (skin-to-skin), min	198.3 ± 62.9 190.0 (155.0, 233.5)	191.1 ± 59.0 184.5 (148.0, 224.0)	0.170	
Cross-clamp time, min	75.0 ± 26.8 70.0 (56.0, 92.0)	71.7 ± 26.3 68.0 (54.0, 88.0)	0.111	
Cardiopulmonary bypass time, min	103.9 ± 39.3 98.0 (76.0, 126.0)	102.1 ± 38.1 94.0 (77.0, 121.0)	0.542	
Final valve size, mm	25.0 (23.0, 25.0) 24.7 ± 2.1	23.0 (21.0, 23.0) 22.3 ± 1.5	<0.001	
 19	0 (0.0)	8 (3.3)		
 21	32 (7.4)	97 (39.9)		
 23	133 (30.7)	108 (44.4)		
 25	161 (37.2)	27 (11.1)		
 27	75 (17.3)	3 (1.2)		
 29	32 (7.4)	0 (0.0)		
Implant details				
 First implant success	432 (99.8)	242 (99.6)	1.000	
 Second implant with INSPIRIS RESILIA	1 (0.2)	1 (0.4)	1.000	
 Paravalvular leak (final)	5 (1.2)	1 (0.4)	0.427	
Intraprocedural deaths	0 (0.0)	0 (0.0)	1.000	
AVR: aortic valve replacement; CABG: coronary artery bypass graft; IQR: interquartile range; MIS: minimally invasive surgery; SD: standard deviation.

Discharge characteristics

The overall hospital stay during SAVR was similar between female and male patients in the matched cohort [median 8.0 (IQR 6.0–10.0) vs 8.0 (IQR 7.0–11.5) days, P = 0.144; Table 3). There was no difference in the length of stay in the intensive care unit and in the duration of mechanical ventilation in both groups. A similar proportion of patients were discharged alive (females 99.6% and males 99.3%; Supplementary Material, Table S3). The majority of patients were discharged to home after the operation, followed by discharge to a rehabilitation unit or another hospital.

Table 3: Discharge details—propensity matched cohort

Mean ± SD or median (IQR) or n (%)	Male, N = 433	Female, N = 243	P-value	
Hospital stay, days	9.0 ± 4.5 8.0 (6.0, 10.0)	9.9 ± 6.5 8.0 (7.0, 11.5)	0.144	
Discharged alive	428 (99.3)	242 (99.6)	1.000	
Discharge to			0.428	
 Home	257 (59.6)	151 (62.1)		
 Other hospital	33 (7.7)	25 (10.3)		
 Rehabilitation unit	135 (31.3)	66 (27.2)		
 Other	3 (0.7)	0 (0.0)		
 Death	3 (0.7)	1 (0.4)		
ICU stay, h	46.4 ± 54.7 24.0 (21.0, 48.0)	52.0 ± 59.0 25.0 (22.0, 62.0)	0.449	
Mechanical ventilation, h	11.9 ± 39.5 7.0 (4.0, 10.0)	10.1 ± 15.0 7.0 (5.0, 10.0)	0.609	
ICU: intensive care unit; IQR: interquartile range; SD: standard deviation.

Clinical outcomes

Both in the entire and the PS-matched cohorts, no significant differences were observed in the incidence of clinical outcomes at 2 years, including endocarditis, thromboembolic events, valve-related dysfunction, repeated procedure, permanent pacemaker implant and valve-related bleeding between males and females undergoing SAVR ± CABG/root replacement (Supplementary Material, Table S4; Table 4) as well as in patients undergoing isolated AVR (Supplementary Material, Table S5). The 2-year survival rate in the PS-matched cohort was 96.2% [95% confidence interval (CI): 94.3–98.1%] in males and 96.3% (CI: 93.9–98.9%) in females (P = 0.920); no differences were observed in the total cohort (Fig. 2, Supplementary Material, Fig. S1). Although the rate of valve thrombosis at 2 years seemed to be higher in females (1.3% vs 0.4% in the PS-matched cohort), the difference did not reach statistical significance (P = 0.093).

Figure 2: Kaplan–Meier survival curve at 2-year all-cause mortality stratified by sex—propensity score matched cohort. PS: propensity score.

Table 4: Two-year clinical outcomes—propensity score matched cohort

	Early (≤30 days)	Late (>30 days to 2 years)	Freedom from events at 2 years, % (95% CI)		
n (%)	Male, N = 433	Female, N = 243	Male, 732 vy	Female, 400 vy	Male	Female	P-value	
All-cause mortality	5 (1.2)	1 (0.4)	10 (1.4)	7 (1.8)	96.2 (94.3, 98.1)	96.3 (93.9, 98.9)	0.920	
 Cardiovascular-related	5 (1.2)	1 (0.4)	7 (1.0)	3 (0.8)	97.0 (95.4, 98.7)	98.1 (96.3, 100.0)	0.365	
 Valve-related	2 (0.5)	0 (0)	5 (0.7)	2 (0.5)	98.3 (97.0, 99.6)	98.9 (97.5, 100.0)	0.394	
 Valve-related—unknown	1 (0.2)	0 (0)	2 (0.3)	4 (1.0)	99.1 (98.2, 100.0)	98.1 (96.2, 100.0)	0.233	
Prosthesis endocarditis	0 (0)	0 (0)	4 (0.5)	2 (0.5)	99.0 (98.0, 100.0)	99.0 (97.5, 100.0)	0.909	
Thromboembolic events	11 (2.5)	4 (1.6)	4 (0.5)	4 (1.0)	95.9 (93.8, 97.9)	95.8 (93.0, 98.7)	0.967	
 Stroke	7 (1.6)	4 (1.6)	0 (0)	1 (0.3)	98.1 (96.7, 99.5)	97.4 (95.2, 99.7)	0.594	
Valve thrombosis	0 (0)	0 (0)	3 (0.4)	5 (1.3)	99.7 (99.1, 100.0)	98.0 (96.0, 100.0)	0.093	
Valve-related dysfunction	1 (0.2)	0 (0)	3 (0.4)	5 (1.3)	99.5 (98.8, 100.0)	98.6 (97.1, 100.0)	0.196	
Repeat procedure	1 (0.2)	0 (0)	0 (0)	3 (0.8)	99.8 (99.3, 100.0)	99.0 (97.5, 100.0)	0.096	
Permanent pacemaker	18 (4.2)	9 (3.7)	2 (0.3)	2 (0.5)	95.2 (93.2, 97.3)	95.4 (92.7, 98.1)	0.944	
Valve-related bleeding	43 (9.9)	29 (11.9)	2 (0.3)	3 (0.8)	89.5 (86.7, 92.5)	86.6 (82.4, 91.1)	0.282	
CI: confidence interval; vy: valve years.

The majority of patients requiring a repeat procedure at the 2-year follow-up in our study did so due to the presence of the endocarditis; in 1 patient, a repeat procedure was due to valve thrombosis whereas another one had a moderate paravalvular leak. One patient underwent a valve-in-valve procedure due to AS. Furthermore, all patients reporting prosthetic valve thrombosis at 2 years in our study either initiated or changed anticoagulation therapy and had a regression and good prosthesis function as shown by the decreased mean pressure gradient in the follow-up echocardiogram. For 1 patient, valve thrombosis was reverted despite the absence of anticoagulant therapy. Therefore, the presence of the valve thrombosis was mostly subclinical and did not lead to detrimental clinical consequences after SAVR using a biosprosthetic valve.

DISCUSSION

Key findings of this propensity score matched study based on 2-year data from the INDURE and IMPACT registries were (i) females exhibited higher surgical risk (EuroSCORE II and STS scores), had higher symptomatic burden (NYHA functional class III/IV and angina CCS III/IV) than males with similar comorbidity prevalences; (ii) females received smaller valves than males, with a median diameter of 23 mm compared to 25 mm in males; (iii) both male and female patients experienced similar hospital lengths of stay in the intensive care unit after SAVR; (iv) patients demonstrated comparable outcomes at 2 years after SAVR, suggesting that sex-related differences observed at baseline did not impact clinical outcomes.

In the overall population (n = 993), the proportion of female patients undergoing SAVR from 2019 to 2021 was lower compared to the proportion of male patients [258 (26.0%) vs 735 (74.0%)]. This disparity suggests a lower incidence of SAVR in females than males, consistent with findings reported in prior literature [2, 3, 7]. Despite a similar prevalence of AS [13], the specific factors contributing to the lower rate of SAVR in women remain unclear. Several studies have proposed possible explanations, such as the insidious onset of the disease in females, delayed diagnosis, conservative management, less frequent referrals to specialists and fewer diagnostic tests conducted among women [2, 14, 15]. However, it is important to note that our study did not focus on the male–female disparity in the incidence of SAVR, the time that elapsed between diagnosis and intervention or the urgency of SAVR, which represents a limitation of our findings.

Several previously published studies [2, 9, 16–18] have investigated sex-related differences in patients undergoing SAVR. These studies consistently reported that females undergoing SAVR tended to be older, exhibited advanced NYHA symptoms and angina symptoms and had higher surgical risks compared to males. Our study results align with these findings, because females exhibited significantly higher EuroSCORE II and STS scores in both cohorts (P < 0.001), indicating a greater surgical risk profile in females. Nevertheless, there was no significant difference in age between males and females in our study, and they were younger (both sexes) than the populations studied earlier [15, 17, 18]. Furthermore, in our cohort, females showed advanced NYHA functional class III/IV and angina CCS III/IV symptoms compared with the males (P < 0.001), indicating a heightened cardiac risk and symptomatic burden than male patients; this trend was consistent with the observations of previous studies [9, 17, 18]. Contrary to the lower comorbidity prevalence observed among female patients undergoing SAVR in the PARTNER trial [15] and the study by Triboulloy et al. [17], our study did not reveal significant differences between males and females. Nonetheless, our study did note a higher prevalence of previous MIs among males, aligning with the findings of Hernandez-Vaquero et al. [16] and Tribouilloy et al. [17].

Notably, a significant difference was observed in implanted valve sizes between the sexes, with females being implanted with smaller valves than males (median diameter 23 vs 25 mm; P < 0.001). This difference is attributed to anatomical differences, with women typically having smaller hearts and aortic annuli [19] than men. Consequently, the need for smaller aortic bioprostheses in women has been recognized in previous research and is associated with increased risk in SAVR [20]. Therefore, it underscores the importance of selecting valve size based on precise in vivo measurements of the patient's specific annular dimensions.

Despite significant differences in baseline characteristics, indicating a high surgical risk among females in our study, the 2-year outcomes after SAVR revealed comparable outcomes in both sexes. However, the existing literature shows varied findings. For instance, a study by Kulik et al. comparing long-term outcomes of SAVR over 5.6 years reported a significantly lower reoperation rate in women (comorbidity-adjusted hazard ratio 0.4; 95% CI: 0.2–0.9) and a higher incidence of late stroke (hazard ratio 1.7; 95% CI: 1.1–2.7) compared to men, indicating that sex-related differences in long-term SAVR outcomes exist [21]. Despite these discrepancies, women exhibited better overall long-term survival than men in their study. Similarly, findings from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, with a median follow-up of 4 years, revealed that females exhibited lower total mortality and a reduced rate of ischaemic cardiovascular events compared to men, independent of confounding factors, despite similar AS progression and greater severity in females based on echocardiographic indices [22]. On the other hand, another baseline-matched retrospective study reported comparable long-term survival benefits in females at a 5-year follow-up. However, men faced a higher risk of bleeding, endocarditis and early reoperation after SAVR [9]. Thus, collectively, these studies suggest that female sex does not significantly impact the long-term survival of SAVR when preoperative characteristics are adjusted between the 2 sexes.

Limitations

Our study did not capture data on matching-based postoperative ventricular remodelling and prosthetic valve performance following surgery, which could elucidate casual factors impacting the outcome for males and females. Additionally, we did not gather information on the timing of intervention and the urgency of SAVR. Furthermore, our study lacks data on prosthetic–patient mismatch, a common complication of cardiac surgery [23].

CONCLUSION

Women undergo SAVR less frequently and exhibit a higher risk profile, posing unique challenges for cardiac surgeons. Nevertheless, our analysis reveals that the 2-year clinical outcomes of SAVR are similar between the sexes when baseline characteristics are matched. These findings highlight the importance of considering sex-related factors in evaluating surgical risk and treatment strategies for patients having SAVR.

Supplementary Material

ivae140_Supplementary_Data

ACKNOWLEDGEMENTS

We are thankful to Cornelia Deutsch, Nataliya Trushina, Anjaly Vijayan and Violetta Hachaturyan (Institute for Pharmacology and Preventive Medicine, Cloppenburg, Germany) for their excellent research contribution with statistical analysis and manuscript writing.

FUNDING

This work was supported with a research grant provided by Edwards Lifesciences (Nyon, Switzerland) to the sponsor Institute for Pharmacology and Preventive Medicine, Cloppenburg, Germany.

SUPPLEMENTARY MATERIAL

Supplementary material is available at ICVTS online.

Conflicts of interest: Andreas Zierer, Ruggero De Paulis, Farhad Bakhtiary, Thierry Bourguignon, Nikolaos Bonaros, Michael Borger, Justus Strauch, Peter Bramlage and Bart Meuris have received lecture fees and/or research support from Edwards Lifesciences. Richard Feyrer, Andreas Liebold and Andreas Vötsch have received lecture fees/proctoring fees from Edwards Lifesciences. Beate Botta received research support from Edwards Lifesciences for their institution. The institutions of all authors representing study centres have received patient inclusion-based funding; these authors have no conflicts of interest to disclose.

DATA AVAILABILITY

The data sets generated and analysed during the current study may be available from the corresponding author upon reasonable request.

Author contributions

Andreas Zierer: Conceptualization; Data curation; Investigation; Methodology; Supervision; Writing—review and editing. Ruggero De Paulis: Conceptualization; Data curation; Investigation; Methodology; Supervision; Writing—review and editing. Farhad Bakhtiary: Conceptualization; Data curation; Investigation; Methodology; Supervision; Writing—review and editing. Ali El-Sayed Ahmad: Conceptualization; Data curation; Investigation; Methodology; Writing—review and editing. Martin Andreas: Data curation; Investigation; Writing—review and editing. Rüdiger Autschbach: Data curation; Investigation; Writing—review and editing. Peter Benedikt: Data curation; Investigation; Writing—review and editing. Konrad Binder: Data curation; Investigation; Writing—review and editing. Nikolaos Bonaros: Data curation; Investigation; Writing—review and editing. Michael Borger: Conceptualization; Data curation; Investigation; Methodology; Supervision; Writing—review and editing. Thierry Bourguignon: Conceptualization; Data curation; Investigation; Methodology; Supervision; Writing—review and editing. Sergio Canvas: Data curation; Investigation; Writing—review and editing. Enrico Coscioni: Data curation; Investigation; Writing—review and editing. Francois Dagenais: Data curation; Investigation; Writing—review and editing. Philippe Demers: Data curation; Investigation; Writing—review and editing. Oliver Dewald: Data curation; Investigation; Writing—review and editing. Richard Feyrer: Data curation; Investigation; Writing—review and editing. Hans-Joachim Geißler: Data curation; Investigation; Writing—review and editing. Martin Grabenwöger: Data curation; Investigation; Writing—review and editing. Jürg Grünenfelder: Data curation; Investigation; Writing—review and editing. Sami Kueri: Data curation; Investigation; Writing—review and editing. Ka Yan Lam: Data curation; Investigation; Writing—review and editing. Thierry Langanay: Data curation; Investigation; Writing—review and editing. Günther Laufer: Data curation; Investigation; Writing—review and editing. Wouter van Leeuwen: Data curation; Investigation; Writing—review and editing. Rainer Leyh: Data curation; Investigation; Writing—review and editing. Andreas Liebold: Data curation; Investigation; Writing—review and editing. Giovanni Mariscalco: Data curation; Investigation; Writing—review and editing. Parwis Massoudy: Data curation; Investigation; Writing—review and editing. Arash Mehdiani: Data curation; Investigation; Writing—review and editing. Renzo Pessotto: Data curation; Investigation; Writing—review and editing. Francesco Pollari: Data curation; Investigation; Writing—review and editing. Gianluca Polvani: Data curation; Investigation; Writing—review and editing. Alessandro Ricci: Data curation; Investigation; Writing—review and editing. Jean-Christian Roussel: Data curation; Investigation; Writing—review and editing. Saad Salamate: Data curation; Investigation; Writing—review and editing. Matthias Siepe: Data curation; Investigation; Writing—review and editing. Pierluigi Stefano: Data curation; Investigation; Writing—review and editing. Justus Strauch: Data curation; Investigation; Writing—review and editing. Alexis Theron: Data curation; Investigation; Writing—review and editing. Andreas Vötsch: Data curation; Investigation; Writing—review and editing. Alberto Weber: Data curation; Investigation; Writing—review and editing. Olaf Wendler: Data curation; Investigation; Writing—review and editing. Matthias Thielmann: Data curation; Methodology; Writing—review and editing. Matthias Eden: Conceptualization; Data curation; Software; Writing—review and editing. Beate Botta: Conceptualization; Formal analysis; Funding acquisition; Methodology; Project administration; Resources; Validation; Writing—original draft; Writing—review and editing. Peter Bramlage: Conceptualization; Formal analysis; Funding acquisition; Methodology; Resources; Software; Validation; Writing—original draft; Writing—review and editing. Bart Meuris: Conceptualization; Data curation; Investigation; Methodology; Supervision; Writing—review and editing.

Reviewer information

Interactive CardioVascular and Thoracic Surgery thanks the anonymous reviewers for their contributions to the peer review process of this article.

ETHICAL APPROVAL/PATIENT CONSENT

The study was approved by the institutional review board/ethics committee at each participating centre, and written informed consent was obtained from each patient before enrolment.

 

Presented at the EACTS 2023, Vienna, 07 October 2023.

ABBREVIATIONS

AS Aortic stenosis

CABG Coronary artery bypass graft

CCS Canadian Cardiovascular Society

IQR Interquartile range

NYHA New York Heart Association

PSM Propensity score matching

SAVR Surgical aortic valve replacement

STS Society of Thoracic Surgeons
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