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Sex-Based Differences in Coronary and Structural Percutaneous Interventions

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Sex-Based Differences in Coronary and Structural Percutaneous Interventions Cardiol Ther (2020) 9:257–273 https://doi.org/10.1007/s40119-020-00176-5 REVIEW Sex-Based Differences in Coronary and Structural Percutaneous Interventions Ashley Mohadjer . Garrett Brown . Syed R. Shah . Charishma Nallapati . Nida Waheed . Anthony A. Bavry . Ki Park Received: April 20, 2020 / Published online: May 21, 2020 Ó The Author(s) 2020 ABSTRACT few decades. As therapies have expanded in complex coronary and structural interventions, In the current state of interventional cardiol- the nuances of treating certain populations ogy, the ability to offer advanced therapies to have emerged. In particular, the role of sex- patients who historically were not surgical based anatomic and outcome differences has candidates has grown exponentially in the last been increasingly recognized. As guidelines for cardiovascular prevention and treatment for certain conditions may vary by sex, therapeutic interventions in the structural and percuta- neous coronary areas may also vary. In this review, we aim to discuss these differences, the current literature available on these topics, and areas of focus for the future. Digital Features To view digital features for this article go to https://doi.org/10.6084/m9.figshare.12264233. Keywords: Aortic valve disease; Interventional & A. Mohadjer Á G. Brown Á K. Park ( ) cardiology; Mitral valve disease; Percutaneous Division of Cardiovascular Medicine, University of Florida, Gainesville, FL, USA coronary intervention; Sex-related disparities; e-mail: [email protected]fl.edu Sex-specific factors S. R. Shah Department of Internal Medicine, North Florida Regional Medical Center, University of Central Florida (Gainesville), Gainesville, FL, USA C. Nallapati Á N. Waheed Department of Internal Medicine, University of Florida, Gainesville, FL, USA A. A. Bavry Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern, Dallas, TX, USA G. Brown Division of Cardiovascular Medicine, University of South Florida, Tampa, FL, USA 258 Cardiol Ther (2020) 9:257–273 United States, more women have died from Key Summary Points cardiovascular disease compared to men [2]. This is partly due to women having different Why carry out this study? anatomic and risk factor profiles relevant to procedural indications and outcomes. Addi- More women have died from tionally, women with coronary artery disease cardiovascular disease than men in recent typically have worse outcomes compared to years due to different risk factors and men [3]. Thus, significant sex-related disparities anatomical differences that impact persist, resulting in suboptimal treatment of therapeutic procedural indication and women. Even when multiple social and eco- outcome. nomic factors are considered such as level of Women are often underrepresented in education, income, and access to care, this cardiovascular trials, leading to a one-size- inconsistency continues to be significant [4]. fits-all approach to cardiovascular care. Although many reasons have been elucidated to explain this disparity, much remains unclear. What are the sex-based differences in Some of the sex-related differences in outcomes anatomy and outcomes discussed in the may be partially explained by variation in the literature, and how does this impact pathophysiology of certain diseases. For exam- percutaneous coronary and structural ple, women with acute coronary syndrome are intervention? less likely to have significant obstructive coro- What was learned from the study? nary artery disease, but are more likely to have plaque erosion and thrombus formation when With regard to coronary intervention, compared to men with similar symptoms [5–7]. female patients are observed to have It appears that the less frequent presence of increased in-hospital mortality and in- obstruction may be related to different patterns hospital complications compared to men. of atherosclerosis. Analyses have shown that coronary vessels in women appear to have a Sex-specific differences in major vascular more diffuse atherosclerotic disease pattern complications, patient–prosthesis with involvement of the entire circumference of mismatch, and pacemaker implantation the artery [6]. Thus, coronary arteries appear are present in patients undergoing TAVR. more ‘‘normal’’ at the time of angiography in Differences in outcomes after mitral valve nearly 50% of women, without evidence of repair among sexes have not consistently flow-limiting stenosis [8]. Thus, the approach to demonstrated statistical significance, but coronary intervention for stenoses that are sig- may depend on etiology of the mitral nificant may be different for women versus men valve disease. based on the pattern of atherosclerosis. Further study is needed to examine sex- Additionally, some of the differences in specific differences so that we may better outcomes may be related to variation in coro- select therapies for patients. nary anatomy by sex. Coronary vessels in women on average are smaller than those of men, up to 10% smaller, independent of body size [9, 10]. Studies looking at major epicardial coronary diameters on cardiac computed BACKGROUND tomography imaging in patients with minimal coronary artery calcium (scores \ 100 Agatston score) found significantly smaller vessel diame- Sex-related differences in the pathophysiology, ter in women compared to men. This difference treatment, and outcomes of cardiovascular dis- persisted after adjustment for body mass index, eases have been studied in greater detail in the body surface area, age, and left ventricular mass last few decades [1]. Since the mid-1980s, in the [11]. It has been suggested that sex hormones Cardiol Ther (2020) 9:257–273 259 may play a role in the size variation due to their women in cardiovascular trials, and recommend impact on arterial remodeling [10]. Addition- in-depth analysis of social and behavioral bar- ally, female vessels may show impaired riers to better engage female trial participants vasodilator response, though this is somewhat [13]. While the relevance of sex-based differ- controversial [9, 10]. They may also have ences does depend on the exact condition or increased vascular stiffness compared to men intervention, consideration of these factors is [9, 10]. This can affect hemodynamic assess- essential to avoid treating patients according to ment of coronary lesions, which can have a ‘‘one size fits all’’ strategy. In this review, we implications for long-term outcomes of percu- aim to discuss these sex-specific differences, the taneous coronary intervention (PCI). current literature available on these issues, and Finally, we must also be aware of the differ- areas to focus on in the future. We also high- ences regarding female representation in evi- light anatomic structural differences between dence-based therapies and interventions. While women and men which may affect structural the proportion of women undergoing certain and coronary interventions (Fig. 1). This review interventions varies, women continue to be is based on previously conducted studies and underrepresented in cardiovascular trials and does not contain any studies with human par- on average comprise only 25% of clinical ticipants or animals performed by any of the investigation [12]. Fortunately, awareness of authors. this important issue has increased, and more research is being done to understand sex-speci- fic aspects of care. A position piece published in PERCUTANEOUS CORONARY 2019 highlighted that many sex-specific differ- INTERVENTIONS ences are unveiled in post hoc analyses or sys- tematic reviews. The authors suggested that Stents differences in risk/decision-making, communi- cation, and investigator engagement may be Since the era of Andreas Gruentzig and initial among the reasons for underrepresentation of balloon angioplasty, the field of PCI has Mitral Valve • More likely to have primary MR • Smaller le ventricular volumes and EROA with ischemic MR Aorc Valve • Smaller Le Ventricular Oulow Tract • Smaller Aorc Annulus and Root Coronary Arteries • Smaller epicardial coronary vessel diameter • Decreased vasodilatory response • Increased vascular sffness Femoral Artery • Smaller Peripheral Vasculature • Increased Peripheral Vascular Tortuosity Fig. 1 Anatomic features in women affecting coronary and structural interventions. MR mitral regurgitation; EROA effective regurgitant orifice area 260 Cardiol Ther (2020) 9:257–273 dramatically changed our ability to treat diameter stents. As stent technology advances patients with obstructive coronary disease. to reduce short- and long-term complications, it Contemporary studies comparing outcomes by is unknown whether these adverse outcomes sex have shown mixed results with female sex are affected by sex. There has been improved being associated with variable mortality rates insight into this subject from work supported [14–16]. However, these studies did not account through the Society for Cardiovascular Angiog- for non-traditional cardiac risk factors including raphy and Intervention (SCAI) [31]. As part of depression, which maybe more prevalent in their women’s initiative, Women in Innovation females and is shown to be associated with and Drug-Eluting Stents (WIN-DES) was created adverse outcomes in cardiovascular patients to gather and analyze data regarding PCI in [17]. Many studies are outdated in the current women [31]. A large multicentered registry era where routine use of prasugrel and ticagrelor sponsored by WIN-DES assessed differences in is common. Hence, whether sex-based differ- outcomes of DES in
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