Author + information
- Molly Szerlip, MD∗ ()
- ↵∗Reprint requests and correspondence:
Dr. Molly Szerlip, Department of Interventional Cardiology, The Heart Hospital Baylor Plano, 4716 Alliance Boulevard, Pavilion Two, Suite 340, Plano, Texas 75093.
Female sex has been an independent predictor of worse outcomes after surgical aortic valve replacement (SAVR). Over the past decade, transcatheter aortic valve replacement (TAVR) has become the standard of care for treatment of severe symptomatic aortic stenosis in high-risk and inoperable patients. In contradistinction to the SAVR data, TAVR outcomes data from the initial pivotal randomized trials and sponsor’s post-approval registries have shown a survival benefit for female patients compared with male patients. This benefit occurs despite higher periprocedural vascular and bleeding complication rates in female patients. The exact reasons as to why female sex in TAVR confers a survival benefit compared with male sex, especially when it is diametrically the opposite of SAVR, have yet to be determined (1–4).
In this issue of the Journal, Chandrasekhar et al. (5) report the largest series to date of patients undergoing TAVR and analyze the outcomes according to sex. This study compared in-hospital and 1-year outcomes post-TAVR between male and female patients from the Society of Thoracic Surgeons/American College of Cardiology (STS/ACC) Transcatheter Valve Therapy (TVT) Registry. This real-world experience reflects the clinical trial experience. The study examined >23,000 patients receiving TAVR between 2011 and 2014 with an almost equal proportion of female and male patients (49.9% and 51.1%, respectively). Female patients were in general older and had higher STS scores but were less likely to have pre-existing coronary artery disease, previous myocardial revascularization, atrial fibrillation, diabetes, and lung disease. However, they were more likely to have a lower glomerular filtration rate, moderate to severe mitral regurgitation, and porcelain aorta. Female patients were also more likely to be treated by using a nontransfemoral access (45.0% vs. 35.0%) and were more likely to have a surgical cutdown (36.8% vs. 32.4%). During the TAVR procedure, female patients were more likely to be converted to open surgery for complications such as aortic dissection, annular rupture, and coronary occlusion. As expected, they also had a higher incidence of vascular complications. However, none of these increased risk factors or periprocedural complications translated into an increase in mortality for women at discharge or at 1 year. In fact, at 1 year, women demonstrated higher survival (78.7% vs. 75.5%; hazard ratio: 0.73; 95% confidence interval: 0.63 to 0.85; p < 0.001). These outcomes data confirm the results of the previous randomized trials and are indicative that the trial results are generalizable to the treated population after commercial approval; that being said, it remains a subject of speculation as to why there is a survival difference benefiting female patients undergoing TAVR, especially because this outcome is exactly the opposite of SAVR outcomes according to sex.
Despite female patients being older than their male counterparts and deemed to be more debilitated, deconditioned, and frail, they had fewer comorbid conditions than male patients, which could lead to mortality (5). These comorbidities included less coronary artery disease, resulting in less revascularization with percutaneous coronary intervention and coronary artery bypass graft, less peripheral vascular disease, atrial fibrillation, and chronic obstructive pulmonary disease. This lower incidence of risk factors could potentially explain the lower mortality. Although women had less peripheral vascular disease overall, they had more vascular complications periprocedurally, likely due to smaller access blood vessels with relatively large delivery sheaths. Some data, however, suggest that despite higher vascular complications, there is currently a lower impact on mortality due to the ability to address and repair most of these complications by using an endovascular approach (4). Female patients also had better initial left ventricular function and, after valve implantation, had a better cover index than male patients. It should also be noted that most of the patients in this study population had the balloon-expandable valve (Edwards Sapien, Edwards Lifesciences, Irvine, California) and that the second-generation Sapien XT 29 valve was not available during most of the time period of this study. Thus, only 12% of male patients received the 29-mm valve in this study compared with the PARTNER IIA (Placement of Aortic Transcatheter Valves) Sapien 3 cohort, in which 35% of the male patients received the 29-mm valve (6). This factor could have adversely affected male survival by causing both a higher incidence of patient prosthesis mismatch and significant paravavular leak. Lastly, there may be a difference in the myocardial structural changes between sexes because female patients are known to undergo greater regression of left ventricular hypertrophy after aortic valve replacement than male patients. Male patients with aortic stenosis have been shown to have more cardiac fibrosis as a consequence of aortic stenosis and thus less left ventricular mass regression after aortic valve replacement (7).
One should, however, interpret the results of this study by Chandrasekhar et al. (5) with caution. The findings of this study are only applicable to the population that was studied and should not necessarily be extrapolated to lower risk populations or to patients who receive newer generation valves. We recently reported sex-specific outcomes of TAVR in the PARTNER IIA S3 high-risk and intermediate-risk cohorts at the 2016 Transcatheter Cardiovascular Therapeutics conference (6). In this high-risk and intermediate-risk cohort, there was no difference at 1 year in survival or any other major outcome between female and male patients despite a continued higher incidence in procedural vascular complications in female patients. Why this better survival benefit that was seen in higher risk female patients undergoing TAVR may not be present in lower risk female TAVR patients is not readily apparent. Thus, the survival advantage of being female may not always be true.
Has technology and expertise in performing TAVR eliminated the female survival advantage or is the PARTNER III data just an anomaly? Time will only tell as new evidence continues to be generated. As it stands now, being female is truly an advantage.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Szerlip has served as a speaker and proctor for Edwards Lifesciences; as a consultant and speaker for Medtronic; and as a speaker for Abbott Vascular.
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